2025 ACC_AHA_ACEP 指南：急性冠脉综合征患者的管理

Writing Committee Members\*

Sunil V.Rao, MD, FACC, FSCAI, Chair; Michelle L.O’Donoghue, MD, MPH, FACC, FAHA, Vice Chair; MarcRuel, MD, MPH, FACC, FAHA, Vice Chair; TanveerRab, MD, FACC, MSCAI, JC Liaison†; Jaqueline E.Tamis-Holland, MD, FACC, FAHA, FSCAI, JC Liaison†; John H.Alexander, MD, MHS, FACC, FAHA; UsmanBaber, MD, MS, FACC, FSCAI; HeatherBaker, EdD‡; Mauricio G.Cohen, MD, FACC, FSCAI; MercedesCruz-Ruiz, CHWI‡; Leslie L.Davis, PhD, RN, ANP-BC, FACC, FAHA; James A.de Lemos, MD, FACC, FAHA; Tracy A.DeWald, PharmD, MHS, BCPS-AQ Cardiology; Islam Y.Elgendy, MD, FACC, FAHA, FSCAI; Dmitriy N.Feldman, MD, FACC, FSCAI§; AbhinavGoyal, MD, MHS, FACC, FAHA; IjeomaIsiadinso, MD, MPH, FACC; VenuMenon, MD, FACC, FAHA; David A.Morrow, MD, MPH, FACC, FAHA; DebabrataMukherjee, MD, MS, FACC, FAHA, MSCAI; ElkePlatz, MD, MS, FACEP; Susan B.Promes, MD, MBA, FACEP ‖ ; SigridSandner, MD, MS; YaderSandoval, MD, FACC, FSCAI; RachelSchunder, MA¶; BinitaShah, MD, MS; Jason P.Stopyra, MD, MS#; Amy W.Talbot, MPH¶; Pam R.Taub, MD, FACC; Marlene S.Williams, MD, FACC\*\*

Aim: The “2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes” incorporates new evidence since the “2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction” and the corresponding “2014 AHA/ACC Guideline for the Management of Patients With Non–STElevation Acute Coronary Syndromes” and the “2015 ACC/AHA/SCAI Focused Update on Primary Percutaneous Coronary Intervention for Patients With ST-Elevation Myocardial Infarction.” The “2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes” and the “2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization” retire and replace, respectively, the “2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease.”

Methods: A comprehensive literature search was conducted from July 2023 to April 2024. Clinical studies, systematic reviews and meta-analyses, and other evidence conducted on human participants were identified that were published in English from MEDLINE (through PubMed), EMBASE, the Cochrane Library, Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline.

Structure:

Many recommendations from previously published guidelines have been updated with new evidence, and new recommendations have been created when supported by published data.


TABLE OF CONTENTS

Abstract . . . . . . . . . . . . . . . . . . . . eXXX Top Take-Home Messages. . . . . . . . . . . .eXXX Preamble. . . . . . . . . . . . . . . . . . . .eXXX 1. Introduction. . . . . . . . . . . . . . . . .eXXX 1.1. Methodology and Evidence Review. . .eXXX 1.2. Composition of the Writing Committee. . . . . . . . . . . . . . eXXX 1.3. Guideline Review and Approval. . . . .eXXX 1.4. Scope of the Guideline. . . . . . . . .eXXX 1.5. Class of Recommendation and Level of Evidence. . . . . . . . . . . eXXX 1.6. Abbreviations. . . . . . . . . . . . . eXXX 2. Overview of ACS. . . . . . . . . . . . . . eXXX 2.1. Definition and Classification of ACS. . eXXX 3. Initial Evaluation and Management of Suspected ACS. . . . . . . . . . . . . . .eXXX 3.1. Initial Assessment of Suspected ACS. . . . . . . . . . . . . . . . . eXXX 3.1.1. Prehospital Assessment and Management Considerations for Suspected ACS. . . . . . .eXXX 3.1.2. Initial In-Hospital Assessment of Patients With Confirmed or Suspected ACS. . . . . . . . eXXX 3.1.3. Risk Stratification Tools for Patients With STEMI and NSTE-ACS. . . . . . . . . . eXXX 3.2. Management of Patients Presenting With Cardiac Arrest. . . . . . . . . . eXXX 4. Standard Medical Therapies for STEMI and NSTE-ACS. . . . . . . . . . . . . . .eXXX 4.1. Oxygen Therapy. . . . . . . . . . . .eXXX 4.2. Analgesics. . . . . . . . . . . . . . eXXX 4.3. Antiplatelet Therapy. . . . . . . . . .eXXX 4.3.1. Aspirin. . . . . . . . . . . . .eXXX 4.3.2. Oral P2Y12 Inhibitors During Hospitalization. . . . . . . . .eXXX 4.3.3. Intravenous P2Y12 Inhibition. . . . . . . . . . . .eXXX 4.3.4. Intravenous Glycoprotein IIb/IIIa Inhibitors. . . . . . . . eXXX 4.4. Parenteral Anticoagulation. . . . . . .eXXX 4.5. Lipid Management. . . . . . . . . . .eXXX 4.6. Beta-Blocker Therapy. . . . . . . . . eXXX 4.7. Renin-Angiotensin-Aldosterone System Inhibitors. . . . . . . . . . . eXXX 5. STEMI Management: Reperfusion Strategies. . . . . . . . . . . . . . . . . .eXXX 5.1. Regional Systems of STEMI Care. . . .eXXX 5.2. Reperfusion at PCI-Capable Hospitals. . . . . . . . . . . . . . . eXXX 5.2.1. PPCI in STEMI. . . . . . . . .eXXX 5.2.2. Urgent CABG Surgery. . . . . eXXX 5.3. Reperfusion at Non–PCI-Capable Hospitals. . . . . . . . . . . . . . . eXXX 5.3.1. Timing and Choice of Agent for Fibrinolytic Therapy. . . . .eXXX 5.3.2. Coronary Angiography and PCI After Fibrinolytic Therapy. . . . . . . . . . . . . . . . . . . . . . .eXXX 6. NSTE-ACS: Routine Invasive or Selective Invasive Initial Approach. . . . . . . . . . . eXXX 6.1. Rationale and Timing for a Routine Invasive or Selective Invasive Approach. . . . . . . . . . . . . . .eXXX 7. Catheterization Laboratory Considerations in ACS. . . . . . . . . . . . . . . . . . . eXXX 7.1. Vascular Access Approach for PCI. . . eXXX 7.2. Use of Aspiration Thrombectomy. . . .eXXX 7.3. Use of Intracoronary Imaging. . . . . .eXXX 7.4. Management of Multivessel CAD in ACS. . . . . . . . . . . . . . . . eXXX 7.4.1. Management of Multivessel CAD in STEMI. . . . . . . . .eXXX 7.4.2. Management of Multivessel CAD in NSTE-ACS. . . . . . .eXXX 8. Cardiogenic Shock Management. . . . . . .eXXX 8.1. Revascularization in ACS With Cardiogenic Shock. . . . . . . . . . eXXX 8.2. MCS in Patients With ACS and Cardiogenic Shock. . . . . . . . . . eXXX 9. ACS Complications. . . . . . . . . . . . . eXXX 9.1. Mechanical Complications. . . . . . . eXXX 9.2. Electrical Complications and Prevention of Sudden Cardiac Death After ACS. . . . . . . . . . . eXXX 9.3. Pericarditis Management After MI. . . eXXX 9.4. Management of LV Thrombus After MI. . . . . . . . . . . . . . . .eXXX 10. In-hospital Issues in the Management of ACS. . . . . . . . . . . . . . . . . . . . eXXX 10.1. Cardiac Intensive Care Unit. . . . . . eXXX 10.2. Management of Anemia in ACS. . . . eXXX 10.3. Telemetry and Length of Stay. . . . . eXXX 10.4. Noninvasive Diagnostic Testing Prior to Hospital Discharge. . . . . . .eXXX 10.5. Discharge Planning. . . . . . . . . . eXXX 10.5.1. Patient Education. . . . . . . eXXX 10.5.2. Postdischarge Follow-Up and Systems of Care Coordination. . . . . . . . . .eXXX 10.5.3. Cardiac Rehabilitation. . . . . eXXX 11. Discharge: Long-Term Management and Secondary Prevention. . . . . . . . . . . . eXXX 11.1. DAPT Strategies in the First 12 Months Postdischarge. . . . . . . eXXX 11.1.1. Antiplatelet Therapy in Patients on Anticoagulation Postdischarge. . . . . . . . . eXXX 11.2. Reassessment of Lipid Levels Postdischarge. . . . . . . . . . . . .eXXX 11.3. SGLT-2 Inhibitors and GLP-1 Receptor Agonists. . . . . . . . . . .eXXX 11.4. Use of Chronic Colchicine. . . . . . . eXXX 11.5. Immunization. . . . . . . . . . . . . eXXX 12. Evidence Gaps and Future Directions. . . . .eXXX References. . . . . . . . . . . . . . . . . . . eXXX Appendix 1. . . . . . . . . . . . . . . . . . . eXXX Author Relationships With Industry and Other Entities�������������������������������������������������������������eXXX Appendix 2. . . . . . . . . . . . . . . . . . . eXXX Reviewer Relationships With Industry and Other Entities�������������������������������������������������������������eXXX

## TOP TAKE-HOME MESSAGES

1. Dual antiplatelet therapy is recommended for patients with acute coronary syndromes (ACS). Ticagrelor or prasugrel is recommended in prefer ence to clopidogrel in patients with ACS who are undergoing percutaneous coronary intervention (PCI). In patients with non–ST-segment elevation

ACS who are scheduled for an invasive strat egy with timing of angiography to be ${>}24$ hours, upstream treatment with clopidogrel or ticagrelor may be considered to reduce major adverse car diovascular events. 2. Dual antiplatelet therapy with aspirin and an oral P2Y12 inhibitor is indicated for at least 12 months as the default strategy in patients with ACS who are not at high bleeding risk. Several strategies are available to reduce bleeding risk in patients with ACS who have undergone PCI and require antiplatelet therapy: (a) in patients at risk for gas trointestinal bleeding, a proton pump inhibitor is recommended; (b) in patients who have tolerated dual antiplatelet therapy with ticagrelor, transi tion to ticagrelor monotherapy is recommended ≥ 1 month after PCI; or (c) in patients who require long-term anticoagulation, aspirin discontinua tion is recommended 1 to 4 weeks after PCI with continued use of a P2Y12 inhibitor (preferably clopidogrel). 3. High-intensity statin therapy is recommended for all patients with ACS, and with the option to initi ate concurrent ezetimibe. A nonstatin lipid-lower ing agent (eg, ezetimibe, evolocumab, alirocumab, inclisiran, bempedoic acid) is recommended for patients already on maximally tolerated statin who have a low-density lipoprotein cholesterol level of ≥ 70 mg/dL (1.8 mmol/L). It is reasonable in this high-risk population to further intensify lipidlowering therapy if the low-density lipoprotein cholesterol level is 55 to <70 mg/dL (1.4 to ${<}1.8$ mmol/L) and patient is already on a maximally tol erated statin. 4. In patients with non–ST-segment elevation ACS who are at intermediate or high risk of ischemic events, an invasive approach with the intent to pro ceed with revascularization is recommended during hospitalization to reduce major adverse cardiovas cular events. In patients with non–ST-segment ele vation ACS who are at low risk of ischemic events, a routine invasive or selective invasive approach with further risk stratification is recommended to help identify those who may require revasculariza tion and to reduce major adverse cardiovascular events. 5. Two procedural strategies are recommended in patients with ACS who are undergoing PCI: (a) radial approach is preferred over femoral approach in patients with ACS undergoing PCI to reduce bleeding, vascular complications, and death; and (b) intracoronary imaging is recommended to guide PCI in patients with ACS with complex coronary lesions.

6. A strategy of complete revascularization is rec ommended in patients with ST-segment elevation myocardial infarction or non–ST-segment eleva tion ACS. The choice of revascularization method (ie, coronary artery bypass graft surgery versus multivessel PCI) in non–ST-segment elevation ACS and multivessel disease should be based on the complexity of the coronary artery disease and comorbid conditions. PCI of significant nonculprit stenoses for patients with ST-segment eleva tion myocardial infarction can be performed in a single procedure or staged with some preference toward performing multivessel PCI in a single procedure. In patients with ACS and cardiogenic shock, emergency revascularization of the cul prit vessel is indicated; however, routine PCI of non–infarct-related arteries at the time of PCI is not recommended.

7. Based on one trial, use of the microaxial flow pump in selected patients with cardiogenic shock related to acute myocardial infarction is reason able to reduce death. However, complications such as bleeding, limb ischemia, and renal failure are higher with the microaxial flow pump com pared with usual care. Therefore, careful atten tion to vascular access and weaning of support is important to appropriately balance the benefits and risks.

8. Red blood cell transfusion to maintain a hemo globin of $10~\mathsf{g}/\mathsf{d L}$ may be reasonable in patients with ACS and acute or chronic anemia who are not actively bleeding.

9. After discharge, focus on secondary prevention is fundamental. A fasting lipid panel is recommended 4 to 8 weeks after initiating or adjusting the dose of lipid-lowering therapy. Referral to cardiac reha bilitation is also recommended, with the option for home-based programs for patients unable or unwilling to attend in person.

PREAMBLE

Intended Use

Since 1980, the American College of Cardiology (ACC) and American Heart Association (AHA) have trans lated scientific evidence into clinical practice guide lines with recommendations to improve cardiovascular health. These guidelines, which are based on system atic methods to evaluate and classify evidence, provide a foundation for the delivery of quality cardiovascular care. The ACC and AHA sponsor the development and publication of clinical practice guidelines without com mercial support, and members volunteer their time to the writing and review efforts. Guidelines are official policy of the ACC and AHA. For some guidelines, the ACC and AHA collaborate with other organizations.

Clinical practice guidelines provide recommendations applicable to patients with or at risk of developing cardiovascular disease (CVD). The focus is on medi cal practice in the United States, but these guidelines are relevant to patients throughout the world. Although guidelines may be used to inform regulatory or payer decisions, the intent is to improve quality of care and align with patients’ interests. Guidelines are intended to define practices meeting the needs of patients in most, but not all, circumstances and should not replace clini cal judgment.

## Clinical Implementation

Management, in accordance with guideline recom mendations, is effective only when followed by both practitioners and patients. Adherence to recommen dations can be enhanced by shared decision-making between clinicians and patients, with patient engage ment in selecting interventions on the basis of indi vidual values, preferences, and associated conditions and comorbidities.

## Methodology and Modernization

The ACC/AHA Joint Committee on Clinical Practice Guidelines (Joint Committee) continuously reviews, up dates, and modifies guideline methodology on the basis of published standards from organizations, including the National Academy of Medicine (formerly the Institute of Medicine), 1 and on the basis of internal reevaluation. Similarly, presentation and delivery of guidelines are re evaluated and modified in response to evolving technolo gies and other factors to optimally facilitate dissemina tion of information to health care professionals at the point of care.

Numerous modifications to the guidelines have been implemented to make them shorter and enhance “user friendliness.” Guidelines are written and pre sented in a modular, “knowledge chunk” format in which each chunk includes a table of recommenda tions, a brief synopsis, recommendation-specific sup portive text, and, when appropriate, flow diagrams or additional tables. Hyperlinked references are provided for each modular knowledge chunk to facilitate quick access and review.

In recognition of the importance of cost–value con siderations, in certain guidelines, when appropriate and feasible, an assessment of value for a drug, device, or intervention may be performed in accordance with the ACC/AHA methodology. 2

To ensure that guideline recommendations remain current, new data will be reviewed on an ongoing basis by the writing committee and staff. When applicable,

recommendations will be updated with new evidence, or new recommendations will be created when supported by published evidence-based data. Going forward, tar geted sections/knowledge chunks will be revised dynamically after publication and timely peer review of potentially practice-changing science. The previous designations of “full revision” and “focused update” have been phased out. For additional information and poli cies on guideline development, readers may consult the ACC/AHA guideline methodology manual 3 and other methodology articles. 4–6

Selection of Writing Committee Members

The Joint Committee strives to ensure that the guide line writing committee contains requisite content ex pertise and is representative of the broader cardio vascular community by selection of experts across a spectrum of backgrounds, representing different geographic regions, sexes, races, ethnicities, intellec tual perspectives/biases, and clinical practice settings. Organizations and professional societies with related interests and expertise are invited to participate as collaborators.

Relationships With Industry and Other Entities

The ACC and AHA have rigorous policies and methods to ensure that documents are developed without bias or improper influence. The complete policy on relationships with industry and other entities (RWI) can be found at https://www.acc.org/guidelines/about-guidelines-andclinical-documents/relationships-with-industry-policy . Appendix 1 of the guideline lists writing committee mem bers’ comprehensive and relevant RWI; for the purposes of full transparency, comprehensive and relevant disclo sure information for the Joint Committee is also available at https://www.acc.org/guidelines/about-guidelinesand-clinical-documents/guidelines-and-documentstask-forces .

Evidence Review and Evidence Review Committees

In developing recommendations, the writing com mittee uses evidence-based methodologies that are based on all available data. 3,4 Literature searches fo cus on randomized controlled trials (RCTs) but also include registries, nonrandomized comparative and descriptive studies, case series, cohort studies, sys tematic reviews, and expert opinion. Only key refer ences are cited.

An independent evidence review committee is com missioned when there are ≥ 1 questions deemed of utmost clinical importance and merit formal systematic

review to determine which patients are most likely to benefit from a drug, device, or treatment strategy, and to what degree. Criteria for commissioning an evidence review committee and formal systematic review include absence of a current authoritative systematic review, feasibility of defining the benefit and risk in a time frame consistent with the writing of a guideline, relevance to a substantial number of patients, and likelihood that the findings can be translated into actionable recommenda tions. Evidence review committee members may include methodologists, epidemiologists, clinicians, and biostat isticians. Recommendations developed by the writing committee on the basis of the systematic review are marked “ SR .”

Guideline-Directed Medical Therapy

The term guideline-directed medical therapy encom passes clinical evaluation, diagnostic testing, and both pharmacological and procedural treatments. For these and all recommended drug treatment regimens, the reader should confirm dosage with product insert mate rial and evaluate for contraindications and interactions. Recommendations are limited to drugs, devices, and treatments approved for clinical use in the United States.

Catherine M. Otto, MD, FACC, FAHA Chair, ACC/AHA Joint Committee on Clinical Practice Guidelines

1. INTRODUCTION

1.1. Methodology and Evidence Review

The recommendations listed in this guideline are, whenever possible, evidence based. An initial exten sive evidence review—which included literature de rived from research involving human subjects, pub lished in English, and indexed in MEDLINE (through PubMed), EMBASE, the Cochrane Library, the Agency for Healthcare Research and Quality, and other select ed databases relevant to this guideline—was conduct ed from July 2023 to April 2024. Key search words included but were not limited to the following: AHA/ ACC Clinical Practice Guidelines; acute coronary syndrome(s); angina, unstable; anticoagulants; aspi rin; atrial fibrillation; cardiovascular diseases; coronary artery disease (CAD); coronary syndrome; emergency medical services; fibrinolytic agents; hemorrhage; ma jor adverse cardiovascular events (MACE); morphine; myocardial infarction; non–ST-elevation myocardial infarction (NSTEMI); percutaneous coronary inter vention (PCI); prehospital; revascularization; risk; STelevation myocardial infarction (STEMI); time factors; treatment outcome.

Additional relevant studies, which were published through April 2024 during the guideline writing pro cess, were also considered by the writing committee and added to the evidence tables when appropriate. The final evidence tables summarize the evidence used by the writing committee to formulate recom mendations. References selected and published in the present document are representative and not allinclusive.

1.2. Composition of the Writing Committee

The writing committee consisted of general cardiologists, interventional cardiologists, cardiovascular surgeons, critical care cardiologists, emergency physicians, car diac imaging experts, advanced practice nurses, clinical pharmacists, and lay/patient representatives. The writing committee included representatives from the AHA, ACC, American College of Emergency Physicians (ACEP), Na tional Association of EMS Physicians (NAEMSP), and Society for Cardiovascular Angiography and Interven tions (SCAI). Appendix 1 of the current document lists writing committee members’ comprehensive and rel evant RWI.

1.3. Guideline Review and Approval

The Joint Committee appointed a peer review commit tee to review the document. The peer review committee comprised individuals nominated by the ACC, AHA, and the collaborating organizations. Reviewers’ RWI infor mation was distributed to the writing committee and is published in this document (Appendix 2). This document was approved for publication by the governing bodies of the ACC and the AHA and was endorsed by ACEP, NAEMSP, and SCAI.

1.4. Scope of the Guideline

The scope of the “2025 ACC/AHA/ACEP/NAEMSP/ SCAI Guideline for the Management of Patients With Acute Coronary Syndromes” (referred to hereafter as the “2025 ACS guideline”) is to incorporate new evi dence since the publication of the “2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocar dial Infarction,” 1 the corresponding “2014 AHA/ACC Guideline for the Management of Patients With Non– ST-Elevation Acute Coronary Syndromes,” 2 and the “2015 ACC/AHA/SCAI Focused Update on Primary Percutaneous Coronary Intervention for Patients With ST-Elevation Myocardial Infarction.” 3 The 2025 ACS guideline and the “2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization” 4 retire and replace, respectively, the “2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Pa tients With Coronary Artery Disease.” 5 This guideline

primarily focuses on the management of type 1 acute myocardial infarction (AMI). It can be challenging to dif ferentiate type 1 versus type 2 MI. In cases of uncer tainty and depending on the benefits/risks of a specific diagnostic or therapeutic intervention, it may be appro priate to err on the side of considering an event a type 1 acute coronary syndrome (ACS) event until established to be otherwise.

In the United States, an estimated 805000 AMIs occur annually of which 605000 are first MI events and 200000 are recurrent. 6–8 Although significant morbidity and mortality are associated with MI, 30-day and in-hos pital mortality rates after ST-segment elevation myocar dial infarction (STEMI) have declined in part as a result of timely reperfusion and implementation of evidencebased secondary prevention. 9 From 2011 to 2021 in the United States, the annual death rate attributable to coro nary heart disease declined by $15.0\%.^{6}$ The economic impact of MI is also substantial, with the total annual cost estimated at $\S84.9$ billion, including direct medical expenditures and indirect lost productivity and wages. 10,11 The incidence of MI is higher among Black males com pared with non-Hispanic White males for reasons that are believed to be multifactorial. 12,13 Potential factors that may contribute to this disparity include a higher prevalence of risk factors for CAD, less use of guidelinerecommended medications post-MI, and socioeconomic factors. 14–19 In addition to racial disparities, there are sex-related disparities in the prevalence, presentation, treatment, and outcomes of ACS even after adjusting for confounding factors such as income, geography, and education. 20 Women tend to present with ACS on aver age 10 years later than men and with a greater burden of CVD risk factors. Although chest pain remains the most common symptom of AMI, women are more likely than men to present with accompanying non–chest pain symptoms. 21–24 A delay in recognition of these symp toms can result in delays in presentation, diagnosis, and timely treatment of women with ACS. Studies have also shown that women presenting with ACS are less likely to be correctly diagnosed with an ACS, receive guideline-directed medical therapy, 25–27 and/or undergo coronary revascularization when indicated. 28,29 Bridging these racial and sex gaps will require continued provider education, better understanding of barriers to access ing quality care and guideline-directed medical therapy, and changes at the community and legislative level to address social determinants of health such as income, employment status, neighborhood safety, and access to healthy foods.

In developing the 2025 ACS guideline, the writing committee reviewed previously published guidelines and related scientific statements. Table 1 contains a list of these publications deemed pertinent to this writ ing effort. It is intended for use as a resource, obviating

Table 1. Associated Publications

|Title|Organization| Publication Year (Reference) | |---|---|---| |Guidelines|Guidelines|Guidelines| |Management of blood cholesterol| AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/ AGS/APhA/ASPC/NLA/PCNA |201830| |Prevention, detection, evaluation, and management of high blood pressure in adults| ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ ASH/ASPC/NMA/PCNA |201831| | Primary prevention of cardiovascular disease|ACC/AHA|201932| |Coronary artery revascularization|ACC/AHA/SCAI|20214| | Evaluation and diagnosis of chest pain|AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR|202133| |Prevention of stroke in patients with stroke and transient ischemic attack|AHA/ASA|20２１3４| |Management of heart failure|AHA/ACC/HFSA|20２２35| |Management of patients with chronic coronary disease|AHA/ACC/ACCP/ASPC/NLA/PCNA|202336| |Diagnosis and management of atrial fibrillation|ACC/AHA/ACCP/HRS|202337| |Other Relevant Documents||| |Home-based cardiac rehabilitation|AHA/ACC/AACVPR|201938| |Classification of cardiogenic shock|SCAI,endorsed by ACC/AHA/SCCM/STS|201939| | Contemporary diagnosis and management of patients with myocardial infarction in the absence of obstructivecoronary artery disease |AHA|201940| |Invasive management of acute myocardial infarction complicated by cardiogenic shock|AHA|202141| | Mechanical complications of acute myocardial infarction|AHA|202142| | SHOCK stage classification update| SCAI,endorsed byACC/ACEP/AHA/ESC/ ACVC/ISHLT/SCCM/STS American |202143| |Management of patients at risk for and with left ventricular thrombus| Association. AHA |20２２44| | Cardiac catheterization laboratory management of the comatose adult patient with an out-of-hospital cardiac arrest |AHA|202445|

AACVPR indicates American Association of Cardiovascular and Pulmonary Rehabilitation; AAPA, American Academy of Physician Associates (formerly Ameri can Academy of Physician Assistants); ABC, Association of Black Cardiologists; ACC, American College of Cardiology; ACCP, American College of Clinical Pharmacy; ACEP, American College of Emergency Physicians; ACPM, American College of Preventive Medicine; ACVC, Association for Acute Cardiovascular Care; ADA, American Diabetes Association; AGS, American Geriatrics Society; AHA, American Heart Association; APhA, American Pharmacists Association; ASA, American Stroke Association; ASCVD, atherosclerotic cardiovascular disease; ASE, American Society of Echocardiography; ASH, American Society of Hypertension; ASPC, American Society for Preventive Cardiology; CHEST, American College of Chest Physicians; ESC, European Society of Cardiology; HFSA, Heart Failure Society of America; HRS, Heart Rhythm Society; ISHLT, International Society for Heart and Lung Transplantation; NLA, National Lipid Association; NMA, National Medical Association; PCNA, Preventive Cardiovascular Nurses Association; SAEM, Society for Academic Emergency Medicine; SCAI, Society for Cardiovascular Angiography and Interventions; SCCM, Society of Critical Care Medicine; SCCT, Society of Cardiovascular Computed Tomography; SCMR, Society for Cardiovascular Magnetic Resonance; SHOCK, Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock trial; and STS, Society of Thoracic Surgery.

the need to repeat existing guideline recommendations. Some recommendations have been carried forward from previously published guidelines. If unchanged, those recommendations remain current. Any changes to the formatting or content of these recommendations are defined as:

• Modified: formatting changes (eg, minor verbiage modifications such as PICO[TS] structure) • Adapted: substantive changes (eg, major adapta tions, such as a change in Class of Recommendation [COR], Level of Evidence [LOE], drug, or device classification).

Changes are depicted in a footnote below the recom mendation tables.

1.5. Class of Recommendation and Level of Evidence

The COR indicates the strength of recommendation, en compassing the estimated magnitude and certainty of benefit in proportion to risk. The LOE rates the quality of scientific evidence supporting the intervention on the basis of the type, quantity, and consistency of data from clinical trials and other sources (Table 2). 1

Table 2. Applying the American College of Cardiology/American Heart Association Class of Recommendation and Level of Evidence to Clinical Strategies, Interventions, Treatments, or Diagnostic Testing in Patient Care\* (Updated May 2019)

CLASS(STRENGTH)OFRECOMMENDATION

Suggested phrases for writing recommendations:

·Isrecommended ·Is indicated/useful/effective/beneficial ·Shouldbeperformed/administered/other Comparative-EffectivenessPhrasest: -Treatment/strategy A is recommended/indicated in preference to treatmentB TreatmentAshouldbechosenovertreatmentB

Suggested phrasesforwriting recommendations:

·Isreasonable Canbe useful/effective/beneficial Comparative-EffectivenessPhrasest: Treatment/strategyAisprobablyrecommended/indicated in preference to treatment B ItisreasonabletochoosetreatmentAovertreatmentB

CLASS2b(WEAK) Benefit≥Risk

Suggestedphrasesforwritingrecommendations:

·May/might be reasonable May/mightbeconsidered ·Usefulness/effectivenessisunknown/unclear/uncertainornotwell established

CLASS 3: No Benefit (MODERATE) Benefit=Risk (Generally,LOEAorBuseonly)

Suggested phrases for writing recommendations:

·Isnotrecommended ·Isnotindicated/useful/effective/beneficial Shouldnotbeperformed/administered/other

 Suggested phrases for writing recommendations:

· Potentially harmful · Causes harm ·Associated with excess morbidity/mortality ·Shouldnotbeperformed/administered/other

LEVEL(QUALITY) OFEVIDENCE

LEVELA

High-quality evidencet from more than 1 RCT Meta-analyses of high-qualityRCTs One ormoreRCTs corroborated byhigh-qualityregistry studies

LEVELB-R

(Randomized)

·Moderate-quality evidencetfrom 1 or more RCTs Meta-analysesofmoderate-qualityRCTs

LEVEL B-NR

·Moderate-qualityevidencetfrom1ormorewell-designed,well executednonrandomizedstudies,observationalstudies,orregistry studies Meta-analyses of such studies

LEVELC-LD

Randomized or nonrandomized observational or registry studies with limitations of design or execution Meta-analysesofsuch studies Physiological ormechanisticstudiesinhumansubjects

LEVELC-EO

(Expert Opinion)

·Consensus of expert opinionbased on clinical experience

CORandLOEaredeterminedindependently(anyCORmaybepairedwithanyLOE)

ArecommendationwithLoECdoesnotimplythattherecommendationisweak.Many important clinicalquestions addressed in guidelines do not lend themselves to clinical trials.Although RCTs are unavailable,theremay be avery clear clinical consensus thata

\*The outcome or result of the intervention should be specified (animproved clinical outcomeorincreaseddiagnosticaccuracyorincrementalprognosticinformation)

十Forcomparative-effectivenessrecommendations(COR1and2a;LOEAandBonly) studiesthatsupporttheuseofcomparatorverbsshouldinvolvedirectcomparisons of thetreatmentsorstrategiesbeingevaluated.

+The method of assessing quality is evolving,including the application of standardized,widely-used,andpreferablyvalidated evidencegrading tools;andfor systematic reviews,the incorporation of an Evidence Review Committee.

COR indicates Class of Recommendation;EO,expert opinion;LD,limited data;LOE,Level ofEvidence;NR,nonrandomized;R,randomized;andRCT,randomized controlled trial.

1.6. Abbreviations

|Abbreviation|Meaning/Phrase| |---|---| |ACEi|angiotensin-converting enzyme inhibitor| |ACS|acute coronary syndromes| |AF| atrial fibrillation| |AMI|acute myocardial infarction| |ARB|angiotensin receptor blocker| |ASCVD|atherosclerotic cardiovascular disease| |CABG|coronary artery bypass grafting| |CAD|coronary artery disease| |COD|chronic coronary disease|

|Abbreviation|Meaning/Phrase| |---|---| |CDP|clinical decision pathway| |CICu|cardiac intensive care unit| |OR|cardiac rehabilitation| |cTn|cardiac troponin| |CVD|cardiovascular disease| |DAPT|dual antiplatelet therapy| |DOAC|direct oral anticoagulant| |ECG|electrocardiogram| |FDA|US Food and Drug Administration| |FFR|fractional flow reserve|

|Abbreviation|Meaning/Phrase| |---|---| |FMC|first medical contact| |GLP-1|glucagon-like peptide-1| |HF|heart failure| |hs-cTn|high-sensitivity cardiac troponin| |IABP| intra-aortic balloon pump| |ICD|implantable cardioverter-defibrillator| |IVUS|intravascular ultrasound| |LDL|low-density lipoprotein | |LDL-C|low-densitylipoprotein cholesterol| |L√|leftventricular| |LVEF|left ventricular ejection fraction| |MACE|major adverse cardiovascular event| |MCS| mechanical circulatory support| |MI|myocardial infarction| |MINOCA| Ml with nonobstructive coronary artery disease| |MVD|multivessel disease| |NSTE-ACS|non-ST-segment elevation ACS| |NSTEMI|non-ST-segment elevation myocardial infarction| |OCT|optical coherence tomography| |OR|odds ratio| |PCI| percutaneous coronary intervention| |PCSK9| proprotein convertase subtilisin/kexin type 9| |PPCI|primary percutaneous coronary intervention| |PPI| proton pump inhibitor| |0OL|quality of life| |RCT|randomized controlled trial| |ROSC|return of spontaneous circulation| |SGLT-2|sodium-glucose cotransporter-2| |STEMI| ST-segment elevation myocardial infarction| |UFH|unfractionated heparin| |VA-ECMO|venoarterial extracorporeal membrane oxygenation|

2. OVERVIEW OF ACS

2.1. Definition and Classification of ACS

ACS are typically caused by the disruption (rupture or ero sion) of an unstable coronary artery atherosclerotic plaque with associated partial or complete coronary artery throm bosis and/or microemboli, resulting in diminished blood flow to the myocardium and subsequent myocardial isch emia (Figure 1). 1,2 ACS includes 3 related clinical condi tions that exist along a continuum of severity: (1) unstable angina, (2) non–ST-segment elevation myocardial infarc tion (NSTEMI), and (3) STEMI. The initial diagnosis and classification of ACS should be based on the clinical his tory and symptomatology, interpretation of the ECG (Table 3), and assessment of cardiac troponin (cTn). Unstable an gina is defined by transient myocardial ischemia leading to diminished flow in the absence of significant myonecrosis detected by circulating troponin. In contrast, patients with

 Figure 1. Pathobiology of a Type 1 Myocardial Infarction Due to Atherosclerotic Plaque Disruption.

Progressive lipid accumulation and inflammation within an atherosclerotic plaque may lead to plaque instability. Rupture or erosion of the atherosclerotic plaque and exposure of plaque contents to the circulation may then culminate in activation of the coagulation cascade and subsequent thrombosis. When this occurs in the epicardial vessels of the coronary circulation, the presence of thrombus may compromise flow to the myocardium, leading to myocardial ischemia and eventual myonecrosis. Illustration by Patrick Lane, ScEYEnce Studios. Copyright 2025 American College of Cardiology Foundation, and American Heart Association, Inc.

more prolonged or severe myocardial ischemia are diag nosed with MI and have elevated biomarkers of myonecro sis. Patients with NSTEMI may have a partially occluded coronary artery leading to subendocardial ischemia, while those with STEMI typically have a completely occluded vessel leading to transmural myocardial ischemia and in farction (Figure 2). 3,4 The pathophysiology of ACS can be dynamic and thus patients can rapidly progress from one clinical condition (eg, unstable angina, NSTEMI, STEMI) to another during the course of their presentation and initial evaluation and treatment. Other, less common causes of myocardial ischemia, among others, include coronary ar tery spasm, embolism, and dissection. 3

This guideline will focus on the acute management of ACS, including unstable angina, NSTEMI, and STEMI, which are presumed to result from atherosclerotic plaque rupture or plaque erosion and subsequent thrombosis. 4 Under the Universal Definition of MI, these MI events would be classified as type 1 MI events (Table 4). 4 The diagnostic evaluation of chest pain and the management of type 2 MI, spontaneous coronary artery dissection, and MINOCA (MI with nonobstructive coronary artery disease) are covered in separate documents. 5–8 A detailed descrip tion of the approach to the evaluation of patients with chest pain can be found in the 2021 AHA/ACC/ASE/ CHEST/SAEM/SCCT/SCMR Chest Pain Guideline. 5

Progressive lipid accumulation and inflammation within an atherosclerotic plaque may lead to plaque instability. 1 Rupture of the atherosclerotic plaque and exposure of plaque contents to the circulation may then culminate in activation of the coagulation cascade and subsequent thrombosis. The presence of thrombus may compromise flow to the myocardium, leading to myocar dial ischemia and eventual myonecrosis. Since early ini tiation of therapy is imperative for patients with ACS, a

Table 3. Electrocardiographic Interpretation for Patients With Suspected Acute Coronary Syndromes

||NSTE-ACS|STEMI| |---|---|---| |Electrocardiographic|| New or presumed new ST-elevation of ≥1 mm in ≥2 anatomically contiguous leads (measured at the J-point) in all leads other than V2-V3 and ≥2 mm in men ≥40 y, ≥2.5 mm in men |

Adapted with permission from Thygesen et al. 4 Copyright 2018 The European Society of Cardiology, American College of Cardiology Foundation, American Heart Association, Inc., and the World Heart Federation. Adapted from Kontos et al. 11 Copyright 2022 American College of Cardiology Foundation. \*ST-segment changes may be observed in other conditions including acute pericarditis, left ventricular hypertrophy, LBBB, Brugada syndrome, right ventricular pacing, Takotsubo syndrome, and early repolarization that may obscure the diagnosis of STEMI. 12 New or presumably new LBBB at presentation occurs infrequently and should not be considered diagnostic of AMI in isolation; clinical correlation is required. 13 A new LBBB in an asymptomatic patient does not constitute a STEMI equivalent. 11 ACS indicates acute coronary syndromes; AMI, acute myocardial infarction, LBBB, left bundle branch block; NSTE-ACS, non–ST-segment elevation ACS; and STEMI, ST-segment elevation MI.

high index of suspicion is warranted for those who pres ent with signs and symptoms that could be consistent with myocardial ischemia.

Patients with ACS are at the highest risk for cardio vascular complications acutely, including prior to hospital presentation and during the early hospital phase. With appropriate management, this risk begins to attenuate; however, patients remain at increased risk of recurrent cardiovascular events for several months to years after an ACS. 9 This may in part be related to the acute inflam matory milieu that exists after ACS that may contribute to a heightened risk of recurrent events. Although the point at which a patient transitions from being a patient with an acute ACS to one with more stable or chronic coronary disease (CCD) is incompletely defined, many of the med ications indicated at discharge in patients with an ACS are similar to those for the management of a patient with CCD and should be extended more than a year beyond ACS. The long-term management of patients with ACS who are presumed to now have more stable coronary disease has been described in the 2023 AHA/ACC/ ACCP/ASPC/NLA/PCNA Chronic Coronary Disease Guideline. 10

3. INITIAL EVALUATION AND MANAGEMENT OF SUSPECTED ACS

3.1. Initial Assessment of Suspected ACS

3.1.1. Prehospital Assessment and Management Considerations for Suspected ACS

| Recommendations for Prehospital Assessment and Management Considerations for Suspected Acs Referenced studies that support recommendations are summarized in the Evidence Table. ||| |---|---|---| |COR|LOE|Recommendations| |Suspected AcS|Suspected AcS|Suspected AcS| ||B-NR| 1. In patients with suspected ACS, a 12-lead ECG should be acquired and interpreted within 10 minutes of first medical contact (FMC)* to identify patients with STEMI.12 |

|| Recommendations for Prehospital Assessment and Management Considerations for Suspected AcS (Continued) || |---|---|---| |||| |COR|LOE|Recommendations| ||C-LD| In patients with suspected ACS in which the initial ECG is nondiagnostic of STEMI, serial ECGs toECG is nondiagnostic of STEMI, serial ECGs to detect potential ischemic changes should bedetect potential ischemic changes should be performed, especially when clinical suspicion of | ||C-LD|| ||C-LD|ACS is high, symptoms are persistent, or the| |||clinical condition deteriorates.t3.4| |STEMI|B-NR|| ||B-NR| emergency medical services (EMS) transport to a PCl-capable hospitalerBrimary PCI (PPCI#) is the recommended triage strategy, with an | ||B-NR|| ||B-NR| FMC-to-first-device time system goal of ≤90 minutes.5-7 | |||In patients with suspected STEMl, early advance| ||B-NR|| ||B-NR| notification of the receiving PCl-capable hospital by EMS personnel and activation of the cardiac catheterizationteam isrecommended toreducecatheterizationteam isrecommended toreduce time to reperfusion.1.9 | ||B-NR||

\*FMC indicates the time point when the patient is initially assessed by a health care professional who can obtain and interpret the ECG and deliver initial inter ventions (eg, defibrillation).

†Modified from the “2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR Guideline for the Evaluation and Diagnosis of Chest Pain.” 10

‡PPCI refers to emergency PCI in the setting of STEMI to achieve reperfusion in patients without previous fibrinolytic treatment.

Synopsis

Rapid and coordinated prehospital care plays a critical role in the optimal management of patients with sus pected ACS. 11 Patients with suspected ACS should be transported to the emergency department (ED) by emergency medical services (EMS). 12 In contrast to transport by private vehicle, EMS transport allows for assessment, monitoring, and treatment of poten tially life-threatening conditions such as arrhythmias or cardiac arrest during transport to the ED. 13 In pa tients with suspected ACS, trained prehospital per sonnel should obtain a focused history and physical examination (including assessment of vital signs) and obtain at least one 12-lead ECG so that the elec trocardiographic findings can facilitate next steps in

 Figure 2. Types and Classification of Acute Coronary Syndromes. NSTEMI indicates non–ST-segment elevation myocardial infarction; and STEMI, ST-segment elevation myocardial infarction. Illustration by Patrick Lane, ScEYEnce Studios. Copyright 2025 American College of Cardiology Foundation, and the American Heart Association, Inc.

patient triage. Specifically, patients should be man aged based on the presence or absence of ST-seg ment elevation (or suspected equivalent) on the 12- lead ECG (Table 3 for STEMI electrocardiographic criteria). When possible, electrocardiographic tracings can be transmitted to the PPCI center while en route to help expedite coronary reperfusion upon arrival. Be cause patients with ACS and evidence of heart failure (HF), ventricular arrhythmias, or cardiogenic shock in the prehospital setting are at highest risk for death, identification of these complications is important with subsequent triage of these patients to a PCI-capable

facility when possible (Section 8, “Cardiogenic Shock Management”). 14,15

Recommendation-Specific Supportive Text

1. The early acquisition and recording of prehospital 12-lead ECGs by trained personnel is associated with shorter reperfusion times and lower mortal ity rates from STEMI if this diagnostic information is integrated in patients’ care. 1,2,16 Appropriately trained EMS personnel (ie, paramedics) can inter pret 12-lead ECGs for the identification of STEMI

Table 4. Types of Acute Myocardial Infarction According to the Universal Definition of Myocardial Infarction

|Type1*| Caused by acute coronary atherothrombosis, usually precipitated by atherosclerotic plaque disruption (rupture or erosion) and often associated with partial or completevessel thrombosis. | |---|---| |Type2|Caused by an imbalance between myocardial oxygen supply and demand unrelated to acute coronary atherothrombosis.| |Type3| Cardiac death, with symptoms of myocardial ischemia and presumed ischemic electrocardiographic changes or ventricular arrythmia, before blood samples for cardiac biomarkers can be obtained or increases in cardiac biomarkers can be identified and/or in whom Ml is identified by autopsy. | |Type4| 4a: Peri-PCI Ml caused by a procedural complication and detected |

Adapted with permission from Thygesen et al. 4 Copyright 2018 The European Society of Cardiology, American College of Cardiology Foundation, American Heart Association, Inc., and the World Heart Federation. \*This guideline focuses on the management of type 1 AMI. The diagnostic evaluation of chest pain and the management of type 2 MI, SCAD, and MINOCA are covered in separate documents. 5–8 AMI indicates acute myocardial infarction; CABG, coronary artery bypass grafting; MI, myocardial infarction; MINOCA, MI with nonobstructive coronary artery disease; PCI, percutaneous coronary intervention; and SCAD, spontaneous coronary artery dissection.

with high accuracy. 17 When ST-segment elevation or an equivalent finding is present on the initial ECG (Table 3), initial management and triage should follow the prescribed STEMI treatment algorithm. Electrocardiographic changes are not required to confirm a diagnosis of non–ST-segment elevation ACS (NSTE-ACS).

2. In patients for whom the initial ECG is nondiagnos tic, serial ECGs should be performed during trans port to the hospital especially when clinical suspicion of ACS is high, ischemic symptoms are persistent, or the clinical condition deteriorates. 3,4 Acquisition of subsequent ECGs should not delay transport to a hospital. A second and/or third ECG during EMS transport may identify up to $15\%$ of additional STEMI cases not present on the first ECG. 3 In an observa tional study of 728 patients with suspected ACS who underwent serial prehospital ECGs, a STEMI diagnosis was subsequently made in $8\%$ of patients following an initial nondiagnostic ECG with a median of 12 minutes after the first study. 4 Posterior ECG leads (V7-V9) should be applied in patients with ongoing symptoms and a nondiagnostic ECG and those with ST-segment depressions in leads V1-V3 to assess for ST-segment elevation in the posterior leads, which could indicate a posterior STEMI.

3. PPCI is the preferred method of reperfusion for patients with STEMI. 18 Rapid reperfusion of the infarct-related artery is associated with improved myocardial salvage and improved survival. 19,20 For those who are managed by PPCI, each 30 min utes of delay is associated with an increase in the relative risk of 1-year mortality by $7.5\%$ . 19 As such, evidence supports system-level interventions to reduce time-to-device. 11 Patients with prehospi tal identification of STEMI should preferentially be transported to a PCI-capable hospital with a goal of FMC–to–first-device time of ${\le}90$ min utes. 20 For patients who are directly transported to

the hospital by EMS, the time to treatment goal is defined as the FMC by EMS until coronary reper fusion. Direct transfer to a PCI-capable facility has been associated with shorter reperfusion times and lower mortality compared with transport to the closest non–PCI-capable hospital. 21 In prehospi tal settings where a FMC–to–first-device goal of ≤ 90 minutes is not feasible in patients with STEMI, direct transport to a PCI-capable hospital may be considered if the anticipated FMC-to-device time is $\leq\!120$ minutes. 22,23 See Section 5.1, “Regional Systems of STEMI Care,” for further details.

4. The implementation of several care processes has demonstrated significant reductions in reperfusion times in patients with STEMI when implemented within a regional medical system. 24 These include (1) prehospital catheterization laboratory activation, (2) single call transfer protocol for patients from a non-PCI facility, and (3) ED bypass to transport patients directly to the catheterization laboratory for those presenting by EMS to a PCI-capable hos pital, and for transfers from other facilities. In par ticular, the prehospital activation of catheterization laboratories has been associated with lower short-and long-term mortality in patients presenting with STEMI. 1,8,25 See Section 5.1, “Regional Systems of STEMI Care,” for further details.

3.1.2. Initial In-Hospital Assessment of Patients With Confirmed or Suspected ACS

| Recommendations for Initial In-Hospital Assessment of Patients With||| |---|---|---| |||| |COR|LOE|Recommendations| ||B-NR||

||Recommendations forInitial In-Hospital Assessment of PatientsWith|||| |---|---|---|---|---| |||||| |COR|LOE|Recommendations|Recommendations|| |||||| ||B-NR|| initial ECG is nondiagnostic, serial 12-lead ECGs should be performed to detect potential ischemicshould be performed to detect potential ischemic changes, especially when clinical suspicion ofchanges, especially when clinical suspicion of ACS is high, symptoms are persistent, or clinical condition deteriorates.*3 || ||| In patients with suspected ACS, cTn should be||| ||B-NR| measured as soon as possible, preferably using a high-sensitivity CTn (hs-cTn) assay*4-7 ||| ||| 4. In patients with suspected ACS with an initial hs-cTn or cTn that is nondiagnostic, the ||| ||B-NR| hs-cTn or cTn that is nondiagnostic, the recommended time intervals for repeat ||| ||B-NR|measurements after the initial sample collection||| ||B-NR| (time zero) are 1 to 2 hours for hs-cTn and 3 to 6 hours for conventional cTn assays*8-12 |||

\*Adapted from the “2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR Guideline for the Evaluation and Diagnosis of Chest Pain.” 13

Synopsis

Chest pain is the second most common presenting com plaint to EDs in the United States and has a wide array of potential causes, including ACS. 14 Although most pa tients with chest pain will not have an ultimate diagnosis of ACS, a missed ACS event has significant implications for the patient’s morbidity and mortality. Patients pre senting with signs or symptoms of ACS should undergo a history and physical examination, have timely electro cardiographic acquisition and interpretation (Table 3), and assessment of cardiac troponin, because these tests are central to the diagnosis of MI 15 and will guide patient management (Figure 3). A thorough description of the evaluation of patients with suspected ACS is provided in the “2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/ SCMR Guideline for the Evaluation and Diagnosis of Chest Pain.” 13 Initial medical treatment should begin im mediately for patients with presumed ACS. Urgent echo cardiography, which may include an initial point-of-care ultrasound by trained clinicians, is indicated for patients with cardiogenic shock, hemodynamic instability, or for suspected mechanical complications. For patients with suspected STEMI, rapid reperfusion is critical after di agnosis, and further diagnostic testing should not de lay cardiac catheterization or fibrinolytic therapy unless it would immediately change patient management. For patients who warrant additional testing to confirm a di agnosis of ACS, selection of the method of assessment may encompass several factors, including clinical history, electrocardiographic findings, cardiac biomarkers, pa tient preference, and patient exercise capacity. The use of evidence-based clinical decision pathways (CDPs) has been shown to improve outcomes and direct ap propriate use of resources. 13 CDPs reduce unnecessary testing in $21\%$ to $43\%$ of patients while maintaining a high negative predictive value for major adverse cardio vascular events (MACE). 16–19

Recommendation-specific Supportive Text

1. A focused history and rapid evaluation are criti cal in the assessment of a patient with suspected ACS. 13 Early recognition and initiation of therapy for ACS improves outcomes. 2,20 Rapid electrocar diographic acquisition and interpretation is required for identification of STEMI (Table 3). In patients with NSTE-ACS, the ECG may be normal or demonstrate transient ST-segment elevation (a high-risk finding), ST-segment depression, T-wave inversions, or non specific changes. Of note, ST-segment depression in the anteroseptal leads (V1-V3) could indicate an evolving posterior STEMI and therefore should be managed with a high index of suspicion with a posterior lead ECG if warranted (Table 3). 21 Overall, timely acquisition of an ECG is imperative in patients with a goal to obtain and interpret an ECG by a trained clinician within 10 minutes of presentation. 1 2. An initial nondiagnostic 12-lead ECG does not “rule out” or exclude ACS. Electrocardiographic abnormali ties may be dynamic. A nondiagnostic ECG should be compared to prior ECGs, and a repeat ECG should be obtained during the ED course to assess for evolving changes. 3 Right-sided leads should be obtained in patients with a concern for inferior STEMI to evaluate for right ventricular involvement. 22 Assessment for posterior STEMI with an ECG is described in Table 3. The timing of repeat ECGs should be guided by the patient’s symptoms, especially recurrent chest pain, and any change in clinical condition. 15 In NCDR ACTION (National Cardiovascular Data Registry and Acute Coronary Treatment and Intervention Outcomes Network), $1\,1\%$ of patients ultimately diagnosed with STEMI had an initial ECG that was nondiagnostic, and $72.4\%$ of those patients had a follow-up ECG diagnostic of STEMI within 90 min utes of their initial ECG. 3

3. cTn is the biomarker of choice for assessing patients for possible cardiac injury, with hs-cTn assays being preferred. cTn is central to the diagnosis of AMI. 15 Given its high sensitivity and specificity for myocar dial injury, cTn (I or T) should be utilized to detect or exclude myocardial injury. 7 In the setting of elec trocardiographic evidence of STEMI, reperfusion therapy should not be delayed pending biomarker results. A cTn concentration >99th percentile upper reference limit (a value unique to each assay) is an indicator of myocardial injury. 15,23,24 hs-cTn assays are preferred over conventional cTn assays because the sensitivity and negative predictive values of hscTn are greater. 4,15 In addition, the time interval from chest pain onset to detection of hs-cTn is shorter with hs-cTn compared with conventional cTn assays, lead ing to more rapid “rule in” or “rule out” of ischemia. 25 4. AMI is characterized by a rising and/or falling pattern of cTn values with at least 1 value above the 99th

 Figure 3. Initial Assessment of Patients With Suspected ACS. Colors correspond to Class of Recommendation in Table 2. \*Examples of evidence-based CDPs and definition of low, intermediate, and high risk as defined in the 2021 AHA/ACC/Multisociety Chest Pain Guideline. ACS indicates acute coronary syndromes; CDP, clinical decision pathway; cTn, cardiac troponin; hs-cTn, high-sensitivity cardiac troponin; NSTEMI, non–ST-segment elevation myocardial infarction; and STEMI, ST-segment elevation myocardial infarction. Adapted with permission from Gulati et al. 13 Copyright 2021 American Heart Association, Inc., and American College of Cardiology Foundation.

percentile upper reference limit and believed caused by myocardial ischemia. 21 With the development of hs-cTn assays enabling detection of circulating cTn at lower concentrations, CDPs using serial testing of hs-cTn at presentation (0 hours) and 1 to 2 hours later provide high negative predictive value, as well as accel erated recognition of myocardial injury. 9,1012 Clinicians should be familiar with both the evidence-based CDPs and the analytical characteristics of the cTn assay (ie, limit of quantification, 99th percentile upper reference limit, and criteria for significant change) used in their practice. 24,26 Men and women may have different cut off values with hs-cTn assays. With hs-cTn assays, changes in hs-cTn concentration within the normal reference range but below the 99th percentile upper reference limit can signal cardiac ischemia and may warrant further evaluation. CDPs incorporating hscTn assays with repeat sampling at 1 or 2 hours from ED arrival with calculation of the change or “delta” hs-cTn can identify patients at very low risk (eg, nega tive predictive value ${\tt>}99.5\%$ ) based on assay-specific diagnostic thresholds. 8,11,27–30 However, when using conventional cTn assays, the sampling timeframe is extended to 3 to 6 hours from ED arrival. 31 cTn may be within normal range early after symptom onset espe cially when a high-sensitivity assay is not used. When using a CDP that incorporates a single hs-cTn value, the troponin should be obtained at least 3 hours after the onset of symptoms. 32

3.1.3. Risk Stratification Tools for Patients With STEMI and NSTE-ACS

Synopsis

Substantial variability in short-term mortality and MACE risk exists among patients with ACS. Individual risk

assessment can inform discussions with patients and decisions regarding therapeutic interventions. Several risk scores have been developed and validated to help assess a patient’s short- and long-term risk in estab lished ACS using commonly available clinical and labora tory variables. Although several risk scores exist, 1–3 the GRACE (Global Registry of Acute Coronary Events) and TIMI (Thrombolysis in Myocardial Infarction) Risk Scores for NSTE-ACS and STEMI (Table 5) are well validated and may be useful for helping to guide some therapeutic decisions (Section 6.1., “Rationale and Timing for a Rou tine Invasive or Selective Invasive Approach”). 4–7 These scores are not to be used as diagnostic tools, because they stratify patient risk in the setting of suspected or confirmed ACS. Risk assessment using the GRACE Risk Score has been found to be superior to subjective phy sician assessment for the prediction of death or MI in patients with STEMI or intermediate-risk NSTE-ACS. 8 However, there is insufficient evidence that routine use of risk scores in patients hospitalized for STEMI/ NSTE-ACS translates into reduced risk of cardiovascular events. 9,10

Evidence of HF, such as pulmonary congestion detected by physical examination, chest x-ray, or lung ultrasound, is an important risk marker and integral part of the Killip classification (and thereby the GRACE Risk Score and TIMI Risk Score for STEMI) in patients with ACS. 11–15 Similarly, elevated cardiac biomarkers provide prognostic information and also are key elements of the GRACE and TIMI Risk Scores. Higher cTn levels in patients with ACS are associated with an increased risk of death and MACE 16,17 and similarly may be useful for helping to guide some treatment decisions. 4,18 Several other serum or plasma biomarkers may provide additional prognostic information. In particular, natriuretic peptides (including B-type natriuretic peptide and N-terminal pro

Table 5. Selected Risk Stratification Tools for Patients With ACS

||GRACE Risk Score (2.0)6.7| TIMI Risk Score for Unstable Angina/NSTEMI*4 |TIMI RiskScore for STEMI5| |---|---|---|---| |Target population|ACS|Unstable angina or NSTEMI|STEMI| |Target outcome(s)| In-hospital, 6-mo, 1-y, 3-y, death or death/MI | 14-d all-cause death, Ml, or urgent revascularization | 30-d all-cause death| |Variables used| In-hospital risk score|Age ≥65 y|Age (65-74 y/≥75 y) (2-3 points)| |Variables used|Age| ≥3 risk factors for CAD|Killip classIIV (2 points)*| |Variables used|Killip class|Known coronary stenosis (>50%)|Systolic blood pressure (|

\*Score 1 point for each characteristic that is present. ACS indicates acute coronary syndromes; bpm, beats per minute; CAD, coronary artery disease; CK-MB, creatine kinase-myocardial band; GRACE, Global Registry of Acute Coronary Events; LBBB, left bundle branch block; MI, myocardial infarction; NSTEMI, non–ST-segment elevation myocardial infarction; STEMI, ST-segment elevation myocardial infarction; and TIMI, Thrombolysis in Myocardial Infarction.

B-type natriuretic peptide) may identify those patients with ACS at increased risk of death, HF, and recurrent MACE. 19,20

Early recognition of cardiogenic shock in patients presenting with ACS on FMC by EMS or ED providers is the key to initial triage and risk stratification. 21 Cardio genic shock related to AMI is present in $7\%$ to $10\%$ of the ACS population and carries a high mortality rate. 22 Early and rapid revascularization for cardiogenic shock related to AMI is associated with increased survival, and triage to a PCI-capable hospital and ideally to hospitals providing advanced therapies (eg, mechanical circulatory support [MCS]) is preferred (Section 8.1, “Revascular ization in ACS With Cardiogenic Shock” and Section 8.2, “MCS in Patients With ACS and Cardiogenic Shock”). Several scales are available to determine the severity of shock, and observational data have shown associa tions between severity as assessed by these scales and outcomes. 23

3.2. Management of Patients Presenting With Cardiac Arrest

Recommendations for Management of Patients Presenting With Cardiac Arrest Referenced studies that support recommendations are summarized in the Evidence Table .

|COR|LOE|Recommendations| |---|---|---| ||C-LD|1. Patients with cardiac arrest and STEMI who have| ||C-LD| been resuscitated should preferentially be transferred by EMS to a PPCl-capable center.12 | ||C-LD| been resuscitated should preferentially be transferred by EMS to a PPCl-capable center.12 | | Patients who have been resuscitated after cardiac arrest and are noncomatose or who are comatose with favorable prognostic features and with ||| |evidence of STEMI, should undergo PPCI to||| |improve survival.3-7||| |2b|C-LD|| |2b|C-LD| In patients with cardiac arrest who are comatose, have unfavorable prognostic features, and evi-have unfavorable prognostic features, and evi- dence of STEMI, PPCI may be reasonable after | |2b|C-LD| dence of STEMI, PPCI may be reasonable after individualied assessment.7 | | 3:NO Benefit ||| | 3:NO Benefit || In resuscitated patients who are comatose after cardiac arrest, electrically and hemodynamically stable, and without evidence of STEMI, immediate | | 3:NO Benefit || stable, and without evidence of STEMI, immediate angiography is not recommended due to lack of angiography is not recommended due to lack of benefit.8-14 | | 3:NO Benefit |||

Synopsis

Approximately $10\%$ of patients with STEMI transferred by EMS to the hospital are estimated to have an outof-hospital cardiac arrest. 15 Early recognition of STEMI in resuscitated patients and direct transfer to a PCIcapable center is associated with improved survival. 1,2 Survival-to-hospital discharge in the patient who is co matose with out-of-hospital cardiac arrest is ${<}10\%$ re gardless of etiology. 16 Those with a witnessed arrest and a shockable rhythm have improved survival. Outcomes for patients with STEMI who are awake after resuscitat ed cardiac arrest are comparable to patients with STEMI

who were not in cardiac arrest. 3 For this reason, patients with cardiac arrest who have achieved return of sponta neous circulation (ROSC) and are awake with STEMI on ECG are candidates for PPCI. However, care should be individualized in the comatose patient with rapid assess ment of the patient’s clinical features and cardiac arrest characteristics before proceeding with invasive angiog raphy. 17–19 In contrast, patients who are stable without ST-segment elevation after out-of-hospital cardiac arrest do not require immediate coronary angiography. Coro nary angiography can be deferred pending further risk stratification. 8–13

Recommendation-Specific Supportive Text

1. Observational studies have shown an association between triage of out-of-hospital cardiac arrest patients to a PCI-capable facility with improved outcomes. 1,2,15 Data from the CARES (Cardiac Arrest Registry to Enhance Survival) registry showed that transfer to a PCI-capable center was associated with improved survival in patients with cardiac arrest and STEMI on ECG. EMS should preferentially transfer patients who are comatose after cardiac arrest, have achieved ROSC, and have STEMI on the ECG to a PPCI center. 2 Although the ARREST (Advanced Reperfusion Strategies for Patients With Out of Hospital Cardiac Arrest and Refractory Ventricular Fibrillation) trial did not show a benefit in triaging patients to primary car diac arrest centers, this study evaluated patients without STEMI on the ECG. 20

2. Nearly one-third of patients with cardiac arrest and STEMI on ECG have normal neurologic status on presentation to the ED. 3 Being alert or with partial/ minimal neurologic response on presentation with STEMI after cardiac arrest is an independent pre dictor of survival. Observational studies have dem onstrated comparable survival of the awake patient with STEMI with cardiac arrest to those patients with STEMI without cardiac arrest. 3 For this reason, patients with STEMI who have achieved ROSC and are awake should undergo PPCI (Section 5.2.1, “PPCI in STEMI”).

3. In patients who are comatose after cardiac arrest and have achieved ROSC, but have STEMI on the ECG, an individualized patient assessment for sur vival and futility is essential before proceeding with PCI. Observational data have identified poor prog nostic features that have been validated and incor porated into risk scores for this population. These include unwitnessed arrest, no bystander cardio pulmonary resuscitation, nonshockable rhythm, cardiopulmonary resuscitation ${\tt>}30$ minutes, time to ROSC ${\tt>}30$ minutes, arterial pH <7.2, lactate >7 mmol/L, age ${\tt>}85$ years, and end-stage renal

disease on dialysis. 4,21–30 Although these data sug gest a lack of clear benefit for invasive therapies for patients with STEMI and cardiac arrest who have features indicating an unfavorable neuro logic prognosis, 4,7 this has not been validated in prospective trials. However, for those patients with favorable prognostic features, PPCI is associated with greater survival. 4,7,27

4. Six contemporary trials 9–14 have evaluated the role of emergency angiography in patients who remain comatose after cardiac arrest, do not have ST-segment elevation on a 12-lead ECG, and are electrically and hemodynamically stable. These studies consistently demonstrated a lack of benefit to early angiography when compared with delayed or no angiography in the study population with com parable in-hospital and 6-month survival, as well as neurologic recovery. 31 The relative utility of delayed coronary angiography in this population is uncertain.

4. STANDARD MEDICAL THERAPIES FOR STEMI AND NSTE-ACS

4.1. Oxygen Therapy

|Recommendations for Oxygen Therapy||| |---|---|---| |Referenced studies that support recommendations are summarized||| |COR|LOE|Recommendations| ||| 1. In patients with ACS and confirmed hypoxia (oxygen saturation |

Synopsis

Supplemental oxygen has historically been administered as part of routine care in the management of patients with suspected ACS, although evidence to suggest clini cal benefit in the absence of hypoxia has been lacking. 5 Randomized trials that have enrolled patients with MI and without hypoxia have not demonstrated any clini cal benefit from routine use of supplemental oxygen $(\geq\!6\,\,{\mathsf{L}}/{\mathsf{m i n}})^{2-4,6}$ and have raised some concerns that it may increase myocardial injury by increasing vasocon striction and increasing oxidative stress. 3

Recommendation-Specific Supportive Text

1. Use of supplemental oxygen may provide benefit to patients who present with hypoxia (peripheral capil lary oxygen saturations $\mathord{\leftrightharpoons}90\%$ ), including those who

present with acute or chronic conditions that require the need for supplemental oxygen to achieve an oxygen saturation ${\ge}90\%$ . A systematic review and meta-analysis of RCTs in acutely ill adults from various causes without hypoxia suggested worse short- and long-term mortality with liberal compared with conservative administration of supplemental oxygen. 7 These studies were unable to define the optimal oxygen saturation target range to minimize potential harm and maximize clinical benefit. The observed relationship between oxygenation and outcomes appears to be U-shaped with the lowest mortality rate described for those patients with an $\mathsf{S p o}_{2}$ of $94\%$ to $96\%$ at presentation. 8

2. Several randomized trials have now demonstrated a lack of cardiovascular benefit with routine use of supplemental oxygen in patients presenting with known or suspected AMI and oxygen saturations ${\ge}90\%$ . Although exclusion criteria varied among studies, patients with a home oxygen requirement, active bronchospasm requiring supplemental oxy gen, or with cardiac arrest at presentation were excluded. 2–4,6 The AVOID (Air Versus Oxygen in ST-Segment-Elevation Myocardial Infarction) trial investigated the effects of supplemental oxygen (8 L/min) in patients with STEMI and oxygen satu rations ${\ge}94\%$ and demonstrated a lack of benefit with routine supplemental oxygen, including a pos sible increase in myocardial injury and infarct size. 3 DETO2X-AMI (Efficacy and Outcome Study of Supplemental Oxygen Treatment in Patients With Suspected Myocardial Infarction) evaluated the use of routine supplemental oxygen (6 L/min) in 6629 patients with suspected MI and an oxygen satura tion ${\geq}90\%$ . 2 The use of supplemental oxygen did not reduce all-cause mortality at 1 year and did not reduce rehospitalization with MI. 2,9 A consistent lack of clinical benefit was seen in the study for those with lower baseline oxygen saturations $(90\%–94\%)$ ). 10

4.2. Analgesics

Synopsis

Patients presenting with known or suspected ACS often experience chest pain or other uncomfortable symptoms. Rapid and effective pain relief remains an important treat ment goal to prevent sympathetic activation and adverse clinical sequelae (Table 6). Analgesic therapies may pro vide symptomatic relief, but they have not been shown to improve clinical outcomes in patients with ACS. 1,2 Ni trates and opiate medications remain effective treatment options for management of pain in ACS but should be thoughtfully utilized to prevent potential harm. 3–6 In par ticular, rapid coronary revascularization should be pur sued for patients with ongoing ischemic symptoms that are not relieved with nitrates, and opiates should not be

Table 6. Analgesic Treatment Options for Cardiac Chest Pain

|Medication|Route|Suggested Dosing|Considerations| |---|---|---|---| |Nitroglycerin*|SL (tablets, spray)| 0.3 or 0.4 mg every 5 min as needed up to a total of 3 doses |Use in hemodynamically stable patients with SBP ≥90 mm Hg.| |Nitroglycerin*|| Start at 10 μg/min and titrate to pain relief and hemodynamic tolerability. | Consider for persistent anginal pain after oral nitrate therapy, or if ACS is accompanied by hypertension or pulmonary edema.20-22 Avoid use in suspected RV infarction, SBP |

\*Nitrates should not be administered after recent PDE5 inhibitor use. Avoid use of nitrates/nitroglycerin within 12 h of avanafil, 24 h of sildenafil/vardenafil, or 48 h of tadalafil. 23–25 ACS indicates acute coronary syndromes; PDE5, phosphodiesterase-5 inhibitor; RV, right ventricular; SBP, systolic blood pressure; and SL, sublingual.

used solely to mask these symptoms. Concerns have also been raised that the use of opiates may delay gastric and intestinal absorption of orally administered P2Y12 inhibitors, thereby delaying their pharmacodynamic ef fects in patients undergoing PCI. 7–10 However, the clinical relevance of these pharmacodynamic findings remains disputed. 11–14 Use of nonaspirin nonsteroidal anti-inflam matory drugs should be avoided for management of sus pected or known ischemia pain whenever possible. 15–17 Use of nonsteroidal anti-inflammatory drugs is associated with increased risk of MACE in patients with and without prior cardiac disease, with no documented benefit to sup port routine use in patients with ACS. 15–19

4.3. Antiplatelet Therapy

4.3.1. Aspirin

| Recommendation for Aspirin|||| |---|---|---|---| ||Referenced studies that support recommendations are summarized||| ||||| |COR|LOE|Recommendation|Recommendation| || 1. In patients with ACS, an initial oral loading dose of aspirin, followed by daily low-dosedose of aspirin, followed by daily low-dose aspirin, is recommended to reduce deathaspirin, is recommended to reduce death and MACE.1-5 |||

Synopsis

Aspirin has long been considered an integral part of an tiplatelet therapy to prevent recurrent atherothrombotic events among patients with ACS. 1–3,6 Aspirin reduces the incidence of vascular death after AMI, 3 and in second ary prevention trials (that include patients after MI), it re duces the occurrence of vascular and coronary events, including MI and stroke. 2 Although aspirin use after ACS was traditionally considered lifelong, a strategy of aspirin discontinuation, rather than P2Y12 inhibitor discontinu ation, may now be considered in the maintenance phase after 1 to 3 months in selected patients to reduce risk of

bleeding (Section 11.1, “DAPT Strategies in the First 12 Months Postdischarge”). Aspirin discontinuation after 1 to 4 weeks after PCI is also appropriate for patients on a full-dose anticoagulant in combination with continued use of a P2Y12 inhibitor (Section 11.1.1, “Antiplatelet Therapy in Patients on Anticoagulation Postdischarge”). For patients in whom a history of aspirin hypersensitivity is reported, aspirin desensitization is preferred whenever possible to allow for initial use of dual antiplatelet ther apy. 7–9 The use of a P2Y12 inhibitor is recommended in all patients with ACS regardless of whether they have a history of aspirin hypersensitivity, but should be adminis tered with a loading dose as early as possible for those patients unable to take aspirin at presentation.

Recommendation-Specific Supportive Text

1. Aspirin should be initiated with a loading dose (162-325 mg) in patients with ACS without an absolute contraindication as soon as possible on presentation irrespective of final management strategy (invasive or noninvasive), followed by a daily maintenance dose (Table 7 in Section 4.3.2, “Oral P2Y12 Inhibitors During Hospitalization”). In patients who cannot take oral medication, rectal or intravenous (where available) administration are options for administration. Current evidence sup ports the use of uncoated low-dose aspirin (75- 100 mg) for daily maintenance therapy. The 75 to 100 mg daily dose of aspirin exceeds the minimal effective dose required for platelet thromboxane $\mathsf{A}_{\mathrm{2}}$ suppression, allowing for some interindividual vari ability in drug response. 10 Among patients with ACS referred for an invasive strategy, continued use of full-dose aspirin (300-325 mg daily) for 30 days (following an initial loading dose) was not superior to low-dose aspirin (75-100 mg daily) for reduction of MACE but was associated with increased minor and gastrointestinal bleeding. 4 In an open-label

Table 7. Dosing Considerations for Oral Antiplatelet Therapy in Patients With ACS

|Agent|Setting| Dosing Considerations| |---|---|---| |Aspirin|NSTE-ACS or STEMI| Loading dose 162-325 mg orally. Aspirin (nonenteric coated) should be chewed, when possible, to achieve faster onset of antiplatelet action. Loading dose should be administered for patients already on aspirin therapy. Maintenance dose 75-100 mg orally daily (nonenteric coated) | | Clopidogrel|NSTE-ACS or STEMI without fibrinolytic| Loading dose 300 or 600 mg orally Maintenance 75 mg orally daily | || STEMI with fibrinolytic| Loading dose 300 mg orallyif age ≤75 y; Initial dose 75 mg orallyif age >75 y Maintenance 75 mg orally daily | |Prasugrel| NSTE-ACS or STEMI without fibrinolytic, and undergoing PCI | Loading dose 60 mg orally Maintenance dose 10 mg orally dailyif body weight ≥60 kg and age |

NSTE-ACS indicates non–ST-segment elevation acute coronary syndromes; PCI, percutaneous coronary intervention; and STEMI, ST-segment elevation myocardial infarction.

RCT of patients with established atherosclerotic cardiovascular disease (ASCVD), $35\%$ of whom had a previous MI, no significant differences were observed in MACE or major bleeding for patients treated with 81 mg of aspirin daily and those treated with 325 mg daily, although a high degree of crossover between study arms was observed. 5 Together, these data support the use of low-dose aspirin (75-100 mg daily) for maintenance therapy. Based on an association between aspirin dosing and outcomes in a post hoc analysis of the PLATO (Platelet Inhibition and Patient Outcomes) trial, aspirin doses of $\leq\!100$ mg daily should always be used in patients treated with ticagrelor. 11

4.3.2. Oral P2Y12 Inhibitors During Hospitalization

Recommendations for Oral P2Y12 Inhibitors During Hospitalization Referenced studies that support recommendations are summarized in the Evidence Table .

|COR|LOE|Recommendations| |---|---|---| |AllPatients WithACS(STEMI and NSTE-ACS)||| ||| 1. In patients with ACS, an oral P2Y12 inhibitor should be administered in addition to aspirin to reduce MACE.1-5 | |3: Harm|B-R| In patients with a history of stroke or transient ischemic attack, prasugrel should not be adminis- tered because of worse net clinical outcomes.*+4 | |In-Hospital Management in Patients With NSTE-ACS||| ||B-R| 3. In patients with NSTE-ACS undergoing PCl, prasugrel or ticagrelor is recommended to reduce MACE and stent thrombosis.4-6 | ||B-R| 4. In patients with NSTE-ACS who are managed without planned invasive evaluation, ticagrelor is recommended to reduce MACE.5.7 | ||B-R| In patients with NSTE-ACS, clopidogrel is recommended to reduce MACE when prasugrel or ticagrelor are unavailable, cannot be tolerated, or are contraindicated.1 |

|(Continued)|(Continued)||| |---|---|---|---| |COR|LOE|Recommendations|| |2b|B-NR| In patients with NSTE-ACS planned for an inva- sive strategy with timing of angiography antici- pated to be >24 hours, upstream treatment with clopidogrel or ticagrelor may be considered to American reduce MACE.1.5.8 || |2b|B-NR||| |2b|In-Hospital Management in Patients With STEMI||| |||7. In patients with STEMI managed with PPCI,|| ||B-R| prasugrel or ticagrelor should be administered to|| |||reduce MACE and stent thrombosis.45.9.10|| ||||| ||C-LD| In patients with STEMI managed with PPCl, clopidogrel is recommended to reduce MACE and stent thrombosis when prasugrel or ticagrelor are unavailable, cannot be tolerated, or are contraindicated.11 || ||C-LD||| ||C-LD||| ||||| ||| In patients with STEMI managed with fibrinolytic therapy, clopidogrel should be administered concurrently to reduce death and MACE.23 || |||||

\*Modified from the “2021 ACC/AHA/SCAI Guideline for Coronary Artery Re vascularization” 12 and the †”2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients With Chronic Coronary Disease.” 13

Synopsis

Oral inhibitors of the platelet P2Y12 receptor antago nize adenosine diphosphate–mediated activation of platelets. Across the spectrum of ACS, the addition of a P2Y12 inhibitor to aspirin significantly reduces platelet aggregation and has been shown to reduce the inci dence of recurrent MACE but with an increased risk of bleeding. 1–5,9,10 In addition to receiving aspirin, patients with ACS should therefore be treated with a loading dose of an oral P2Y12 inhibitor followed by daily dos ing (Table 7). The selection of the specific type of oral P2Y12 inhibitor should involve several considerations, including the patient’s anticipated management strat

egy and their risk of bleeding (Figure 4). 1–5,9,10 Clinically available oral P2Y12 inhibitors include clopidogrel, pra sugrel, and ticagrelor. Clopidogrel is the least potent oral P2Y12 inhibitor and requires more time to reach its maximal platelet inhibition after a loading dose, be cause it requires biotransformation in the liver to form its active metabolite. Pharmacodynamic variability in response in clopidogrel has been well described, 14,15 and hyporesponders may be at increased risk of MACE and stent thrombosis when treated with clopidogrel af ter PCI. 16,17 Ticagrelor and prasugrel are more potent than clopidogrel and achieve more rapid onset of in hibition of platelet activation but with increased risk of bleeding compared with clopidogrel. Of note, ticagrelor may cause subjective transient dyspnea in approxi mately $10\%$ to $15\%$ of patients after ACS. 5 The topic of duration of dual antiplatelet therapy is addressed in Section 11.1, “DAPT Strategies in the First 12 Months Postdischarge.”

Recommendation-Specific Supportive Text

1. Several trials have demonstrated the clinical ben efit of oral P2Y12 inhibitors in ACS for reducing MACE but with increased risk of bleeding. In ran domized placebo-controlled trials in both NSTEACS and STEMI, the addition of clopidogrel to aspirin reduced risk of MACE irrespective of man agement strategy. 1–3 In patients with STEMI treated with fibrinolytic therapy, the addition of clopido grel to aspirin reduces 30-day MACE, including

recurrent MI, and improves survival. 2,3 Moreover, in randomized trials, the use of prasugrel and ticagre lor further reduced risk of MACE, as well as stent thrombosis, when compared with clopidogrel in patients with STEMI (not receiving concurrent fibrinolytic therapy) or NSTE-ACS. 4,5 The benefits of oral P2Y12 inhibitors have also been demon strated in patients after coronary artery bypass graft (CABG) surgery. 18–21 Guidance on dosing interruption for patients referred for CABG is in Table 8. Duration of administration after CABG is described in Section 11.1, “ DAPT Strategies in the First 12 Months Postdischarge.”

2. In a secondary analysis of the randomized, double-blind TRITON-TIMI 38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel– Thrombolysis in Myocardial Infarction) of prasugrel versus clopidogrel in addition to aspirin among patients with ACS, subgroup analyses using an outcome of net clinical benefit (MACE events plus bleeding) demonstrated net harm with prasugrel versus clopidogrel among patients with previous transient ischemic attack or stroke. 4 Dose reduc tion of prasugrel should be considered in patients ${\geq}75$ years of age and in those with a body weight ${<\!60~\mathrm{kg}}$ (Table 7).

3. The randomized, double-blind TRITON-TIMI 38 and PLATO trials demonstrated that prasug rel (TRITON-TIMI 38) or ticagrelor (PLATO) reduced the rate of the composite endpoint of

 Figure 4. Initial Choice of P2Y12 Inhibitor in Patients Not Requiring an Oral Anticoagulant. Colors correspond to Class of Recommendation in Table 2. ACS indicates acute coronary syndromes; ASA, aspirin; CABG, coronary artery bypass grafting; NSTE-ACS, non–ST-segment elevation ACS; PCI, percutaneous coronary intervention; and STEMI, ST-segment elevation myocardial infarction.

Table 8. Management of Oral P2Y12 Inhibitors for Patients Who Require CABG Surgery\*

|Clopidogrel|Elective CABG: Interrupt for 5 d before surgery.| |---|---| ||Urgent CABG: Interruption for at least 24 h (ideally) and| ||proceeding earlier than 5 d may be reasonable.| |Prasugrel|Elective CABG: Interrupt for 7 d before surgery.| || Urgent CABG: Interruption for at least 24 h (ideally) and proceeding earlier than 7 d may be reasonable. | ||Elective CABG: Interrupt for 3-5 d before surgery.| |Ticagrelor|Urgent CABG: Interruption for at least 24 h (ideally) and| ||proceeding earlier than 5 d may be reasonable.|

\*For all patients, oral P2Y12 inhibitor should be resumed after surgery when bleeding risk not excessive (typically 24-72 hours). CABG indicates coronary artery bypass grafting.

cardiovascular death, MI, or stroke by $16\%$ to $20\%$ when compared with clopidogrel, as well as reduced the risk of stent thrombosis. 4,5 In the PLATO trial, a nominal reduction in all-cause death with ticagrelor compared with clopido grel was also observed. 5 In TRITON-TIMI 38, the P2Y12 inhibitor (prasugrel or clopidogrel) was only administered in patients with NSTE-ACS once the anatomy was deemed suitable for PCI. In the PLATO trial, $72\%$ were managed with a planned invasive strategy and results in the inva sively managed population were highly consistent with the overall trial for reducing MACE, as well as cardiovascular and all-cause death individually. 6 Both prasugrel and ticagrelor increase the risk of non-CABG major bleeding compared with clopi dogrel. 4,5 Prasugrel has been shown to increase life-threatening bleeds. 4 Limited data exist to compare the efficacy and safety of prasugrel ver sus ticagrelor head-to-head. One open-label ran domized trial reported a lower rate of MACE with similar bleeding with prasugrel administered at the time of PCI compared with ticagrelor used as upstream therapy in patients with ACS undergo ing invasive evaluation. 22

4. The randomized, double-blind PLATO trial of ticagrelor versus clopidogrel included patients with ACS managed with or without a planned invasive strategy. Among the $28\%$ of patients $\mathrm{\Delta}(\mathord{\mathsf{n}}=\!52\,16)$ ) who were managed without a planned invasive strategy, a $15\%$ reduction was observed in the primary endpoint of vascular death, MI, or stroke with ticagrelor versus clopidogrel that was highly consistent with the $16\%$ reduction in MACE in the overall trial. Similarly, the findings for bleeding were consistent with the overall trial result. 5,7

5. In the randomized, double-blind, placebo-con trolled CURE (Clopidogrel in Unstable Angina to Prevent Recurrent Events) trial, among patients with NSTE-ACS receiving aspirin and who were

medically managed or underwent revasculariza tion, the administration of clopidogrel significantly reduced the composite of cardiovascular death, MI, or stroke. 1 Although prasugrel and ticagre lor further reduce major cardiovascular events compared with clopidogrel in patients with ACS undergoing PCI, these more potent agents also further increase the risk of bleeding. 4,5 Clopidogrel is an effective alternative P2Y12 inhibitor for use in patients with high bleeding risk or contraindications to prasugrel or ticagrelor. In an open-label trial with a high crossover rate among older patients with ACS undergoing PCI, patients treated with clopidogrel had a similar rate of ischemic events and less bleeding compared with ticagrelor. 23 Significant interpatient variability in the pharmacodynamic response to clopidogrel has been described. 15

6. In a prospective substudy among the patients who underwent PCI $\mathord{\left<\mathsf{n}=\!}2658\right>}$ ) in the CURE trial, those who were pretreated with clopidogrel (median 6 days) prior to PCI had a significantly lower rate of MACE both before PCI and by 30 days. 8 Clopidogrel is a prodrug that requires metabolism by the cytochrome P450 enzyme system to form its active metabolite and there fore may require several hours before significant antiplatelet effect is observed following a load ing dose. A meta-analysis of trials of clopido grel in patients with ACS undergoing PCI found that pretreatment with clopidogrel significantly reduced the risk for 30-day cardiovascular death or MI. 11 However, less is known regarding the need for pretreatment in the era of more potent P2Y12 inhibitors with more rapid onset of anti platelet action. In a randomized trial of prasugrel pretreatment versus administration at the time of PCI, pretreatment (median of only 4.4 hours) did not improve ischemic outcomes, but significantly increased bleeding. 24 In the PLATO trial, knowl edge of coronary anatomy prior to administra tion of the study drug was not required; however, upstream use of ticagrelor was not specifically compared with a strategy of administration at time of PCI. Therefore, it remains unknown whether a benefit exists for administration of ticagrelor prior to PCI in patients with NSTEACS. For this reason, routine pretreatment in patients undergoing an early invasive manage ment strategy $\langle<\!24$ hours) is not supported by clinical trial data. However, it may be reason able to consider pretreatment with clopidogrel or ticagrelor in patients undergoing an invasive management strategy with the timing of angiog raphy anticipated to be ${\geq}24$ hours from adminis tration of the loading dose.

7. The clinical efficacy of prasugrel and ticagrelor com pared with clopidogrel in TRITON-TIMI 38 and the PLATO trial was consistent in patients undergo ing PPCI or delayed (ie, secondary) PCI after initial therapy for STEMI. 4,5 In the subgroup of patients with STEMI in TRITON-TIMI 38 ( $\mathord{\left/{\vphantom{\left|}}\mathsf{n}\!=\!}3534\right.\kern-\nulldelimiterspace}$ ), prasugrel sig nificantly reduced MACE by $21\%$ and stent throm bosis by $42\%$ at 15 months without a clear excess in bleeding. 9 In the PLATO trial, compared with clopi dogrel, treatment of patients with STEMI undergoing PPCI $\scriptstyle(\mathsf{n}=7544)$ ) with ticagrelor was associated with a consistent trend toward reduction in cardiovascu lar death, recurrent MI, or stroke, as well as a sig nificant reduction in stent thrombosis and an $18\%$ reduction in all-cause death. 10 Both TRITON-TIMI 38 and the PLATO trial permitted study drug adminis tration prior to the initial angiogram for patients with STEMI undergoing primary PCI. In a separate ran domized trial in PPCI for STEMI, allocation to pre hospital ticagrelor or hospital administration did not improve the primary endpoint of coronary reperfu sion prior to the PCI. 25 However, upstream adminis tration of ticagrelor was associated with a reduction in stent thrombosis with similar bleeding between treatment groups. Registry data have also not shown clear clinical benefit for preloading a P2Y12 inhibi tor in patients with STEMI, 26 but a meta-analysis that included patients with STEMI showed that clopido grel pretreatment was associated with a lower risk for MACE without an increase in bleeding. 27

8. Clopidogrel is effective for prevention of stent thrombosis and early recurrent ischemic events in patients with STEMI undergoing PCI. 11 As in patients with NSTE-ACS, in patients with STEMI undergoing PPCI, prasugrel and ticagrelor reduce the risk of recurrent MACE compared with clopi dogrel. 9,10 Administration of clopidogrel is an alter native to prasugrel or ticagrelor in patients with STEMI who are at high bleeding risk or have other contraindications to those agents.

9. In the CLARITY (Clopidogrel as Adjunctive Reperfusions Therapy)-TIMI 28 trial, addition of clopidogrel to aspirin in patients with STEMI who were <75 years of age and received fibrinolytic ther apy reduced the odds of an occluded infarct-related artery at angiography, as well as the composite of cardiovascular death, recurrent MI, or recurrent ischemia requiring urgent revascularization by 30 days. 2 In the randomized, placebo-controlled COMMIT (Clopidogrel and Metoprolol in Myocardial Infarction Trial) study among patients with suspected MI $\textcircled{93\%}$ STEMI, $54\%$ fibrinolytic-treated) receiving aspirin, clopidogrel 75 mg/day (without a loading dose), significantly lowered the risk of the compos ite endpoint of death, reinfarction, or stroke, as well as the endpoint of mortality alone, with a consistent

pattern in the subgroup treated with fibrinolytic. 3 No significant excess was observed in bleeding with clopidogrel versus placebo. Based on the design of these 2 trials, when administered concurrently with fibrinolytic as the reperfusion strategy, clopidogrel is recommended to be administered with a loading dose (300 mg, then 75 mg daily) for patients <75 years of age and starting without a loading dose (75 mg daily) for patients ${\geq}75$ years of age. In patients treated with a fibrinolytic agent who are undergoing subsequent PCI, either clopidogrel or ticagrelor (age <75 years, within 24 hours after a fibrinolytic agent) or prasugrel ${\left(>24\right.}$ hours after a fibrinolytic agent) are alternatives to support PCI. 9–12,28 In a trial of 3799 patients with STEMI who were treated with a fibrino lytic agent, $89\%$ of whom also received clopidogrel at the time of a fibrinolytic agent, randomization to ticagrelor administered at a median of 11.4 hours (interquartile range, 5.8-18.2 hours) after fibrinolytic therapy was noninferior to clopidogrel with respect to major bleeding. 28

4.3.3. Intravenous P2Y12 Inhibition

|Recommendation for Intravenous P2Y12 Inhibition|||| |---|---|---|---| | Referenced studies that support recommendations are summarized |||| |||Recommendation|Recommendation| |COR|B-R| 1. Among patients with ACS undergoing PCI who have not received a P2Y12 inhibitor, intravenous || ||B-R||| | cangrelor may be reasonable to reduce periprocedural ischemic events.*1-4 |B-R|||

\*Reproduced from the “2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization.” 5

Synopsis

Cangrelor is a direct-acting, intravenous antagonist of the P2Y12 receptor characterized by rapid and potent platelet inhibitory effects with restoration of platelet function occur ring within 1 hour of drug discontinuation. 6 These pharma cological properties may be particularly beneficial in clinical scenarios wherein absorption of orally administered P2Y12 inhibitors is impaired or not possible, as well as in patients requiring CABG or other surgery early after PCI when pro longed discontinuation of a P2Y12 inhibitor may not be safe. 7 The safety and efficacy of cangrelor has been com pared with clopidogrel or placebo in 3 RCTs involving pa tients who are P2Y12 inhibitor-naïve and undergoing PCI for stable or acute indications. 1–3 In a patient-level pooled analysis of these studies, cangrelor administered during PCI significantly reduced periprocedural ischemic events albeit at the expense of more frequent minor bleeding. 4 The safe ty and efficacy of cangrelor versus ticagrelor or prasugrel with respect to ischemic events have not been established. The transition from intravenous to oral P2Y12 inhibition is an important consideration to ensure adequate platelet inhi bition on completion of cangrelor infusion (Table 9). 8

Table 9. Transition From Intravenous Cangrelor Infusion to Oral P2Y12 Inhibitor

|Oral P2Y12 inhibitor|Loading Dose| Timing of Loading Dose Ad- ministration | |---|---|---| |Clopidogrel|600mg| Immediately after discontinuation of cangrelor | |Prasugrel|60mg| Immediately after discontinuation of cangrelor | |Ticagrelor|180mg| At any time during or immediately after discontinuation of cangrelor |

Recommendations in table obtained from US Food and Drug Administration labeling for cangrelor. 8

Recommendation-Specific Supporting Text

1. CHAMPION PHOENIX (A Clinical Trial Comparing Cangrelor to Clopidogrel Standard Therapy in Subjects Who Require PCI) examined the effect of cangre lor versus clopidogrel in patients undergoing PCI for acute or stable coronary syndromes. 2 Cangrelor was administered as an intravenous bolus prior to PCI fol lowed by an infusion for at least 2 hours or for the duration of the procedure, whichever was longer. In the control arm, clopidogrel was administered as a 600- or 300-mg loading dose immediately before or after PCI. At 48 hours, the primary endpoint of allcause death, MI, ischemia-driven revascularization, or stent thrombosis was significantly reduced with cangrelor with similar effects observed among those presenting with NSTE-ACS $\mathrm{\Delta}\mathrm{\Omega}_{\backslash\mathrm{\Omega}=28\,10}$ ) or STEMI (n=1991). These results contrast with the earlier neutral findings from the CHAMPION PLATFORM (Cangrelor Versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition) trial and CHAMPION PCI (A Clinical Trial to Demonstrate the Efficacy of Cangrelor), which compared can grelor with placebo and clopidogrel, respectively. 1,3 Differences across trials in the timing of clopidogrel administration and definitions of MI and stent throm bosis may in part account for variability in the inci dence of ischemic events and observed treatment effect. In a pooled analysis of these trials, cangrelor was associated with a significant reduction in peri procedural ischemic events compared with control with no evidence of heterogeneity across types of ACS presentations. 4

Recommendations for Intravenous Glycoprotein IIb/IIIa Inhibitors Referenced studies that support recommendations are summarized in the Evidence Table .

4.3.4. Intravenous Glycoprotein IIb/IIIa Inhibitors

|COR|LOE|Recommendations|Recommendations| |---|---|---|---| |2a||1. In patients with ACS undergoing PCI with large|| |2a|C-LD||thrombus burden, no-reflow, or slow flow, adjunctive| |2a|C-LD|| use of an intravenous or intracoronary glycoprotein | |2a|C-LD||Ilb/lla inhibitor is reasonable to improve procedural| |2a||||

|Recommendations for Intravenous Glycoprotein llb/lla Inhibitors||| |---|---|---| |COR|LOE|| |||Recommendations| |3: Harm|B-R| In patients with ACS, glycoprotein Ilb/lla inhibitors should not be administered routinely due to lack of ischemic benefit and increased risk of bleeding.3-5 | |3: Harm|B-R|| |3: Harm|||

\*Adapted from the “2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization.” 6

Synopsis

Glycoprotein IIb/IIIa receptor inhibitors are parenter ally administered drugs that block platelet aggrega tion by preventing platelet cross-linking via fibrinogen or von Willebrand factor binding to the glycoprotein IIb/IIIa receptor. These agents were first evaluated be fore contemporary antiplatelet and interventional strate gies were introduced and in an era when the time to coronary revascularization was substantially longer than today. Thus, limited data are available for glycoprotein IIb/IIIa receptors in patients receiving more potent P2Y12 inhibitors and in those receiving earlier PCI with contemporary drug-eluting stents that have a lower risk for stent thrombosis than prior generations of stents. In current practice, the role of glycoprotein IIb/IIIa recep tor inhibitors is largely limited to adjunctive use at the time of PCI in patients with large thrombus burden or as “rescue” or “bailout” therapy in patients with PCI com plications such as no-reflow or persistent or recurring thrombus at the lesion. 1

Recommendation-Specific Supportive Text

1. In a study of 452 selected high-risk patients with large anterior STEMI and a large thrombus bur den, adjunctive use of intracoronary abciximab reduced thrombus burden and infarct size. 1 Other trials have also suggested that glycoprotein IIb/IIIa inhibitors can reduce intracoronary thrombus burden in patients with STEMI and NSTE-ACS. 7,8 Thus, glycoprotein IIb/IIIa receptor inhibitors can be considered at the time of PCI for patients with a large coronary thrombus burden or no-reflow or slow flow that is believed to be attributable to distal embolization of thrombus. In clinical trials comparing intravenous and intracoronary admin istration of glycoprotein IIb/IIIa inhibitors, clini cal and bleeding outcomes, as well as thrombus resolution and infarct size, have generally been similar. 2,9,10

2. Multiple strategies have been evaluated for use of glycoprotein IIb/IIIa receptor inhibitors in patients with ACS. “Upstream” administration of these agents is defined as administration of small mol ecule agents (eptifibatide or tirofiban) early after

ACS diagnosis for medical stabilization prior to planned angiography and PCI. In the EARLY-ACS (Early Glycoprotein IIb/IIIa Inhibition in Patients with Non–ST-segment Elevation Acute Coronary Syndrome) trial, 9406 patients with NSTE-ACS were randomized to routine upstream use of eptifi batide (within 8 hours after presentation to the hospital) versus ad hoc adjunctive use at the time of PCI among patients with NSTE-ACS. 4 Ischemic outcomes were not improved and bleeding was increased in the routine upstream eptifibatide arm. An alternative approach is routine adjunctive use of a glycoprotein IIb/IIIa inhibitor at the time of PCI for patients with STEMI or NSTE-ACS. Although early trials performed prior to use of potent P2Y12 inhibitors suggested that this approach improved procedural outcomes and reduced periprocedural myocardial necrosis, studies performed among patients receiving pretreatment with clopidogrel have not confirmed reduction of ischemic events with routine adjunctive glycoprotein IIb/IIIa inhibi tion and have increased bleeding complications. 5,11

4.4. Parenteral Anticoagulation

| Recommendations for Parenteral Anticoagulation Referenced studies that support recommendations are summarized in the Evidence Table. ||| |---|---|---| |COR|LOE|Recommendations| |NSTE-ACS: Upstream* Anticoagulant Therapy||| ||B-R| In patients with NSTE-ACS,intravenous unfractionated heparin (UFH) is useful to reduce ischemic events.+1-4 | ||B-R| In patients with NSTE-ACS in whom an early invasive approach is not anticipated, either enoxaparin or fondaparinux are recommended alternatives to UFH to reduce ischemic events.5-11 | | Anticoagulant Therapy in Patients Undergoing Coronary Revascularization ||| ||C-LD| 3. In patients with ACS undergoing coronary revascularization (CABG or PCI) in the same admission, parenteral anticoagulation should be continued until revascularization to reduce ischemic events.12,13 | | Anticoagulant Therapy to Support PCI in ACS (STEMI and NSTE-ACS) ||| ||C-EO| 4. In patients with ACS undergoing PCl, intravenous UFH is useful to reduce ischemic events.t | ||B-R| 5. In patients with STEMI undergoing PCl, bivalirudin is useful as an alternative to UFH to reduce mortality and bleeding.+1419 | |2b|B-R| 6. In patients with NSTE-ACS undergoing PCI, bivalirudin may be reasonable as an alternative to UFH to reduce bleeding.623 | |2b|B-R| 7. In patients with ACS, intravenous enoxaparin may be considered as an alternative to UFH at the time of PCI to reduce ischemic events.78,24-26 | |3: Harm|B-R| 8. In patients with ACS, fondaparinux should not be used to support PCl because of the risk of catheter thrombosis.527 |

||Recommendations for Parenteral Anticoagulation (Continued)|| |---|---|---| |COR|LOE|Recommendations| |STEMl: Anticoagulant Therapy Treated With Fibrinolytic Therapy||| ||| 9. In patients with STEMI treated with fibrinolytic| |||therapy, parenteral anticoagulation should be| |||continued for the duration of the hospital stay| |||(maximum of 8 days) or until revascularization is| |||performed to reduce ischemic events.10.27-29 | ||| 10.In patients with STEMI treated with fibrinolytic therapy who are not intended to undergo an | ||| 10.In patients with STEMI treated with fibrinolytic therapy who are not intended to undergo an | |||invasive approach, enoxaparin is the recommended| |||anticoagulant to reduce ischemic events.102829| ||B-R|11. In patients with STEMI treated with fibrinolytic| ||B-R|therapy who are not intended to undergo an inva-| ||B-R|sive approach, fondaparinux is a recommended | |||alternative to reduce schemic events.27.30|

\*At the time of diagnosis and prior to invasive coronary angiography if planned. †Adapted or ‡modified from the “2021 ACC/AHA/SCAI Guideline for Coronary Artery Re vascularization.” 31

Synopsis

Parenteral anticoagulation is recommended for all pa tients with ACS, irrespective of the initial treatment strategy, to treat the underlying pathophysiologic pro cess (coronary atherothrombosis) and reduce the risk of recurrent MACE (Table 10). Although eventual di agnostic reclassification can occur (ie, to other non atherothrombotic ACS diagnoses such as coronary spasm or other conditions that can mimic ACS, such as stress cardiomyopathy or myocarditis), initial par enteral anticoagulation is intended to treat thrombus caused by atherosclerotic plaque disruption (rupture or erosion) in patients with presumed type 1 MI. 32 Anti coagulation strategies are to be initiated upstream (at the time of diagnosis and prior to coronary angiogra phy) and to support PCI or other reperfusion therapy. In patients with ACS undergoing PCI, intraprocedural thrombin generation and platelet aggregation may occur, for which reason parenteral anticoagulation is recommended to reduce the risk for thrombotic com plications. 33 The choice of a parenteral anticoagulant can be complex because it is influenced by various fac tors, including vascular access site, renal function, and concomitant use of other antiplatelet or anticoagulant agents. Heparin-induced thrombocytopenia can oc cur with both UFH and low-molecular-weight heparin; in this context, argatroban and bivalirudin are direct thrombin inhibitors that are acceptable alternative an ticoagulants for patients with known heparin-induced thrombocytopenia. 34,35

Recommendation-Specific Supportive Text

1. UFH has traditionally been the preferred anti coagulant to treat patients with NSTE-ACS. 1–4 However, limitations to its use include the lack of

Table 10. Dosing of Parenteral Anticoagulation in ACS

|Drug|Dosing| |---|---| |UFH| Initial therapy: Loading dose 60 IU/kg (max 4000 IU), with initial infusion 12 IU/kg per h (max 1000 IU/h) adjusted to therapeutic aPTT range of 60-80 s. | || To support PCl: In patients who have received prior anticoagulant therapy, additional UFH as needed to achieve an ACT 250-300 s. In patients who have not received prior anticoagulant therapy, 70-100 U/kg initial bolus to achieve target ACT of 250-300 s. | || With fibrinolytic therapy: Loading dose 60 IU/kg (maximum 4000 IU) with initial infusion 12 IU/kg per h (maximum 1000 IU/h) adjusted to therapeutic aPTT range. | |Bivalirudin|To support PCl: 0.75 mg/kg bolus, 1.75 mg/kg per h IV infusion during the PCl procedure.| || Post-PCI infusion for PPCl: 1.75 mg/kg per h for 2-4 h post-PCl.| || In patients with CrCl |

ACS indicates acute coronary syndromes; ACT, activated clotting time; aPTT, activated partial thromboplastin time; CrCl, creatinine clearance; PCI, percutaneous coronary intervention; PPCI, primary percutaneous coronary intervention; and UFH, unfractionated heparin.

a predictable dose response and risk of heparininduced thrombocytopenia. 33 In unstable angina, a meta-analysis including 1353 patients enrolled from 6 randomized studies showed that, in com parison to patients treated with aspirin alone, those treated with aspirin and heparin were at lower, albeit nonstatistically significant, risk for MI or death dur ing the randomized treatment period (relative risk, 0.67 [95% CI, 0.44-1.02]). 3 Its efficacy compared with placebo has not been evaluated in the current era of dual antiplatelet therapy (DAPT) and early revascularization. 33

2. Fondaparinux, a synthetic pentasaccharide that selectively binds antithrombin and causes rapid and predictable inhibition of Factor Xa, was evalu ated in patients with high-risk NSTE-ACS in the OASIS-5 (Fifth Organization to Assess Strategies in Acute Ischemic Syndromes) trial. 5 Fondaparinux was similar to enoxaparin in the risk for ischemic events at 9 days, but it reduced major bleeding. About $40\%$ of the patients underwent PCI, and an increase was observed in the rate of guidingcatheter thrombus formation with fondaparinux $(0.9\%$ versus $0.3\%$ ) compared with enoxaparin. In NSTE-ACS, despite some data favoring the use of enoxaparin over UFH, 11 multiple meta-analyses have not demonstrated compelling superiority in efficacy over UFH. 7,26,36 A meta-analysis comparing low-molecular-weight heparin to UFH in 12171 patients with ACS without ST-segment elevation across 5 randomized trials showed no significant

difference in death or MI (2.2% versus $2.3\%$ ) or in the risk of major bleeding. 36 3. For patients with ACS undergoing coronary revas cularization (CABG or PCI), parenteral antico agulation is indicated until revascularization. The premature discontinuation of anticoagulation is associated with a transient rebound increase in thrombin activity and activated protein C and the reactivation of ischemic events, 12,13 with the great est risk for reinfarction in the first 4 to 8 hours after the discontinuation of anticoagulation. 4. UFH has traditionally been the preferred antico agulant to support PCI in patients with NSTE-ACS. Activated clotting time is used to guide dosing dur ing PCI. 37 Although its pharmacokinetic effects are not always predictable, its anticoagulant effect is reversible with the administration of protamine. 5. Bivalirudin is a direct thrombin inhibitor evaluated in both NSTE-ACS and STEMI that can be used to support PCI. In the BRIGHT-4 (Bivalirudin with Prolonged Full-Dose Infusion during PPCI versus Heparin) trial, 15 which enrolled patients with STEMI undergoing PPCI using radial access $(93\%)$ , bivali rudin was compared with heparin monotherapy in an open-label design. The bivalirudin regimen used included the standard bolus and dosing (0.75 mg/kg, then 1.75 mg/kg per hour) plus a post-PCI infu sion at the full dose (1.75 mg/kg per hour) for 2 to 4 hours. Bivalirudin with the full dose postPCI infusion was superior to UFH in reducing the 30-day composite of all-cause death or BARC (Bleeding Academic Research Consortium) types 3-5 bleeding $(4.39\%$ versus $3.06\%$ ; $\scriptstyle P=0.007.$ ). 15 All-cause death was also reduced with bivalirudin $\it{(3.92\%}$ versus $2.96\%$ ; $P{=}0.04$ ), as well as 30-day stent thrombosis $(0.37\%$ versus $1.1\%$ ; ${\it P}{=}0.00\,1\,5$ ). Based on these results, when bivalirudin is used to support PPCI for STEMI, a postprocedure 2- to 4-hour infusion at full dose is recommended. 15,38,39 6. Meta-analyses comparing bivalirudin versus UFH with or without glycoprotein IIb/IIIa inhibitors in patients with ACS demonstrate that bivalirudin is associated with a lower risk for major bleed ing. 16,17,40 In the context of NSTE-ACS, bivaliru din was evaluated in the ACUITY (A Comparison of Angiomax Versus Heparin in Acute Coronary Syndromes) trial, where bivalirudin was nonin ferior to UFH plus glycoprotein IIb/IIIa inhibitor for the risk of MACE and superior with respect to 30-day major bleeding. 41 The bleeding defi nition used in the study was specific to the ACUITY trial. Bivalirudin was also evaluated in the MATRIX (Minimizing Adverse Hemorrhagic Events by Transradial Access Site and Systemic Implementation of AngioX) trial where it was com pared against UFH alone (ie, without concomitant glycoprotein IIb/IIIa inhibitor). 42 No significant dif ference was observed between the 2 arms with respect to 30-day ischemic or bleeding events. 7. Intravenous enoxaparin compared with UFH reduces the risk for ischemic outcomes without a significant difference in bleeding in the setting of PPCI. In the ATOLL (Acute Myocardial Infarction Treated with Primary Angioplasty and Intravenous Enoxaparin or Unfractionated Heparin to Lower Ischemic and Bleeding Events at Short- and Longterm Follow-up) trial, 24 which enrolled patients presenting with STEMI, the primary endpoint of 30-day incidence of death, complication of MI, procedural failure, or major bleeding occurred in $28\%$ of patients with enoxaparin compared with $34\%$ with UFH ${\it\Delta}^{\prime}P{=}0.06{,}$ ). Although the incidence of primary endpoint was not significantly different between enoxaparin and UFH, the secondary end point of 30-day death, recurrent ACS, or urgent revascularization was significantly lower in the enoxaparin group $\mathcal{(}7\%$ versus $1\uparrow\%$ ; $P{=}0.015$ ). In addition, a net clinical benefit (death, complication of MI, or major bleeding) was observed with enoxa parin compared with UFH ( $10\%$ versus $15\%$ ; $\scriptstyle P=0.03$ ). In a meta-analysis of 10451 patients, intravenous enoxaparin was associated with a sig nificant reduction in death and major bleeding. 26 8. Fondaparinux should not be used as the sole antico agulant to support PCI because of the risk of catheter thrombosis. 5,27,31 In the OASIS-5 trial, an increase was observed in the rate of catheter-related thrombus

with fondaparinux compared with enoxaparin $(0.9\%$ versus $0.4\%$ ). 5 Similar results were observed in the OASIS-6 (The Safety and Efficacy of Fondaparinux versus Control Therapy in Patients with STEMI) trial in which a higher rate of guiding-catheter thrombosis and more coronary complications with fondaparinux were observed when used during PCI. 27

9. In patients with STEMI treated with fibrinolytic therapy, parenteral anticoagulation is recom mended before and after fibrinolytic therapy to reduce ischemic events. In studies of fibrinolytic therapy such as the GUSTO (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries) trial, the ASSENT-3 (Assessment of the Safety and Efficacy of a New Thrombolytic Regimen) trial, or the ExTRACT-TIMI 25 (Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction TreatmentThrombolysis in Myocardial Infarction 25) study, intravenous heparin was administered for at least 48 hours. 10,29,43 In the ExTRACT-TIMI 25 study, the UFH infusion was given for at least 48 hours but could be continued for a longer period at the treating physician’s discretion, whereas the sub cutaneous injections of enoxaparin were contin ued until hospital discharge or for a maximum of 8 days (whichever came first). 10 Patients randomized to enoxaparin had a lower risk of death or nonfa tal recurrent MI through 30 days compared with UFH $(9.9\%$ versus $12.0\%$ ); however, treatment with enoxaparin was associated with an increase in major bleeding $(2.1\%$ versus $1.4\%,$ ). 10

10. In patients with STEMI who received fibrinolytic therapy and who are not planned for an invasive approach, enoxaparin is the preferred anticoagu lant over UFH. 9,10,28,29,44 In the ExTRACT-TIMI 25 study, enoxaparin until hospital discharge or for a maximum of 8 days (whichever came first) was compared with UFH administered for at least 48 hours (could be continued for a longer period at the treating physician’s discretion) in 20506 patients with STEMI receiving fibrinolytic therapy. 10 The primary endpoint of death or nonfatal recurrent MI through 30 days occurred in $12\%$ in the UFH group compared with $9.9\%$ in the enoxaparin group. In a meta-analysis of 14 randomized trials, UFH did not reduce reinfarction or death in patients treated with fibrinolytic therapy. In contrast, low-molecularweight heparin reduced the risk of reinfarction and death compared with placebo and the risk of reinfarction. 45

11. In patients with STEMI who are not likely to undergo an invasive approach, fondaparinux is an alternate anticoagulant that can be used. In the OASIS-6 trial of patients with STEMI who were treated with thrombolytic agents (predominantly streptokinase),

fondaparinux significantly reduced the risk of the primary endpoint of death or reinfarction at 30 days, including a significant reduction in mortality, reinfarction, and severe bleeding when compared with placebo or UFH. 27,30

4.5. Lipid Management

|Recommendations for Lipid Management|||| |---|---|---|---| |||Referenced studies that support recommendations are summarized|| |COR|Recommendations|Recommendations|| ||| 1. In patients with ACS, high-intensity statin therapy is recommended to reduce the risk of MACE.*1-4 || ||| 2. In patients with ACS who are already on maximally tolerated statin therapy with low- density lipoprotein cholesterol (LDL-C)density lipoprotein cholesterol (LDL-C) ≥70 mg/dL (≥1.8 mmol/L), adding a nonstatin≥70 mg/dL (≥1.8 mmol/L), adding a nonstatin lipid-lowering agent is recommended to furtherlipid-lowering agent is recommended to further reduce the risk of MACE.t5-7 || ||B-R| 3. In patients with ACS who are statin intolerant, nonstatin lipid-lowering therapy is recommended nonstatin lipid-lowering therapy is recommended to lower LDL-C and reduce the risk of MACE.8-10 || ||||| |2a|B-R| 4. In patients with ACS who are already on maximally tolerated statin therapy with LDL-C 55 to 69 mg/dL (≥1.4 to ||

†adapted from the “2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients With Chronic Coronary Disease.” 14

Synopsis

The current recommendations focus on patients with recent (ie, within 12 months) ACS. The 2023 AHA/ ACC/ACCP/ASPC/NLA/PCNA CCD guideline pro vides more detailed recommendations on long-term management of lipids in patients with prior ACS. 14 ASCVD event rates are substantially higher in patients with recent ACS than those with CCD, with 1-year rates of cardiovascular death, MI, and ischemic stroke estimated at $10\%$ to $15\%$ after an ACS hospitaliza tion. 15,16 Higher risk among patients with ACS supports more aggressive LDL-cholesterol (LDL-C) targets in pa tients with recent ACS compared with those with CCD (Figure 5). 14–16 RCTs have demonstrated ASCVD event reduction with multiple different pharmacological ap proaches to LDL-C level lowering, with the magnitude of benefit proportional to the degree of LDL-C level low ering. 17 In patients with ACS, RCTs have demonstrated incremental benefit with high- compared with moderateintensity statin therapy in regard to reduction in MACE. 1–4 For patients who do not reach LDL-C treatment goals on maximally tolerated statin therapy, or who are intol erant to statins, several nonstatin therapies, including

ezetimibe, monoclonal antibodies to proprotein conver tase subtilisin/kexin type 9 (PCSK9), and bempedoic acid, can both lower LDL-C levels and improve ASCVD outcomes across diverse populations. 5–10 Inclisiran also lowers LDL-C levels by preventing translation of PCSK9 mRNA, but clinical outcomes studies are not yet avail able (Table 12). Nonetheless, the relative benefit of LDL-C–lowering therapies is expected to be proportional to the observed reduction in LDL-C levels (Tables 11 and 12). 5–11 A lipid profile is recommended as soon as feasible after presentation with ACS (Figure 5), because LDL-C levels decrease modestly beginning 24 hours from symptom onset. 18 Lipid management after hospital discharge is discussed in Section 11.2, “Reassessment of Lipid Levels Postdischarge.”

Recommendation-Specific Supportive Text

1. High-intensity statin regimens lower LDL-C con centration by an average of ${\geq}50\%$ (Table 11). The CTT (Cholesterol Treatment Trialists) meta-analy sis of 5 RCTs showed that LDL-C concentration lowering with high-intensity statins compared with moderate-intensity statins reduces major vascu lar events by approximately $15\%$ in patients with coronary artery disease (CAD). 4 An individual par ticipant meta-analysis of the A to Z (Aggrastat to Zocor) and PROVE IT (Pravastatin or Atorvastatin Evaluation and Infection Therapy)-TIMI 22 trials, both of which were performed in patients stabi lized early after ACS, demonstrated significant reductions in cardiovascular and all-cause death with more intensive versus less intensive statin regimens. 19 The benefit of a high-intensity statin regimen appears early after ACS and persists over time. 3 The benefit of high-intensity statins after ACS appears to be independent of baseline LDL-C concentration. No indication was observed of any safety concerns from achieving very low LDL-C concentrations on statins or other lipid-lowering therapies; therefore, high-intensity statin therapy should not be de-escalated during follow-up in patients who are tolerating treatment. 13

2. Multiple therapeutic options are now available to add to maximally tolerated statin therapy to achieve desired LDL-C goals in patients with ACS (Table 12). In IMPROVE IT (Improved Reduction of Outcomes; Vytorin Efficacy International Trial), addition of ezetimibe to simvastatin 40 mg daily in patients ${<}10$ days after ACS led to a modest but significant reduction in MACE, over a median follow-up of 6 years. 5 Clinical trials of PCSK9 inhibitors have demonstrated a $15\%$ relative risk reduction in MACE over a median of 2 to 3 years including patients ${>}1$ month after ACS. 6,7,20 Greater absolute benefit with PCSK9 inhibitors has been

 Figure 5. Management of Lipid-Lowering Therapy for Patients With ACS. Colors correspond to Class of Recommendation in Table 2. \*Nonstatin LDL-lowering therapy: ezetimibe, PCSK9 inhibitor (alirocumab, evolocumab and inclisiran), and/or bempedoic acid. ACS indicates acute coronary syndromes; LDL, low-density lipoprotein; LDL-C, low-density lipoprotein cholesterol; and PCSK9, proprotein convertase subtilisin/kexin type 9.

 Table 11. Nonstatin Treatment Options for LDL-C Lowering in Patients With ACS Who Are Not at LDL-C Goal on Maximally Tolerated Statin Therapy

|Drug|Mechanism of Action|LDL-C Lowering (%)| Outcomes Study Performed in Patients With Recent ACS? |Potential Adverse Effects| |---|---|---|---|---| |Ezetimibe*|Blocks NPC1L1 cholesterol absorption|15-25|Yes (||

All agents are approved by the FDA. \*The LDL-C lowering potency of ezetimibe is greater when used in combination with statin therapy (approximately $25\%$ LDL-C reduction) than when used as mono therapy $(15\%-20\%)$ ). †Coadministration of bempedoic acid with simvastatin at a dose >20 mg and pravastatin at a dose ${>}40~\mathrm{m}9$ is not recommended due to the increased risk of musclerelated adverse effects from statins. ACS indicates acute coronary syndromes; ASCVD, atherosclerotic cardiovascular disease; CVD, cardiovascular disease; FDA, US Food and Drug Administration; LDLC, low-density lipoprotein cholesterol; NPC1L1, Niemann-Pick C1-Like 1 protein; and PCSK9, proprotein convertase subtilisin/kexin type 9.

Table 12. Statin Classification

|Statin Classification by Expected LDL-C Reduction||| |---|---|---| |High-lntensity Therapy*| Moderate-Intensity Therapyt | Low-lntensity Ther- apy# | |Atorvastatin 40-80 mg|Atorvastatin 10-20 mg| Simvastatin 10 mg| |Rosuvastatin 20-40 mg|Rosuvastatin 5-10 mg|Pravastatin 10-20 mg| ||Simvastatin 20-40 mg|Lovastatin 20 mg| || Pravastatin 40-80 mg|Fluvastatin 20-40 mg| ||Lovastatin 40 mg|| || Fluvastatin XL 80 mg|| ||Fluvastatin 40 mg BID|| || Pitavastatin 1-4 mg||

Modified with permission from Grundy et al. 42 Copyright 2018 American Heart Association, Inc., and American College of Cardiology Foundation. \*Expected LDL-C reduction ${\geq}50\%$ . †Expected LDL-C reduction ${\geq}30\%$ to $49\%$ . ‡Expected LDL-C reduction ${<}30\%$ . BID indicates twice daily; LDL-C, low-density lipoprotein cholesterol.

by $13\%$ in statin-intolerant patients when started ${\tt>}90$ days after ACS. 10

3. Statin intolerance is frequent in clinical practice and the most commonly reported cause is statinassociated muscle symptoms. 27 To consider a patient as having statin intolerance, a minimum of 2 statins should be attempted, including at least 1 at the lowest approved daily dose. 28 Currently available options for patients with complete or partial intolerance to statin therapy include ezeti mibe, PCSK9 inhibitor monoclonal antibodies, inclisiran, and bempedoic acid. Ezetimibe and PCSK9 inhibitors have been demonstrated to be safe and well tolerated and improve lipid param eters in statin-intolerant patients. 8,9 However, outcomes studies using these agents as mono therapy or in combination in statin-intolerant patients are not available. Bempedoic acid is an ATP citrate lyase inhibitor that reduces LDL-C levels by $15\%$ to $25\%$ with low rates of musclerelated adverse effects. 29,30 A combination prod uct that combines bempedoic acid with ezetimibe lowered LDL-C levels by approximately $35\%$ . 31 In the CLEAR Outcomes (Cholesterol Lowering via Bempedoic Acid, an ACL-Inhibiting Regimen) trial, bempedoic acid was compared with placebo in statin-intolerant patients with or at high risk for ASCVD. Patients with ACS within 90 days prior to randomization were excluded from this trial. Mean LDL-C level was 139 mg/dL at enrollment and was reduced by 29 mg/dL with bempedoic acid compared with placebo. MACE was reduced by $13\%$ in the bempedoic acid arm. Bempedoic acid raised uric acid levels in a small subset of patients, and rates of abnormal liver function tests, gout, and gallstones were increased with its use in the trial. 10

4. IMPROVE IT randomized patients post-ACS with LDL-C levels of ≥ 50 mg/dL and $\leq\!125\,\mathrm{\meg/dL}$ ( ≤ 100 mg/dL if on lipid-lowering therapy) to the combination of simvastatin $(40\,\mathrm{\meg})$ ) and ezeti mibe ( $(10~\mathrm{mg})$ ) or simvastatin $(40\;\mathsf{m g})$ ) and placebo (simvastatin monotherapy), with median LDL-C level at enrollment of $69.5\ \mathsf{m g}/\mathsf{d L}$ . The addition of ezetimibe reduced the relative risk of MACE by $6.4\%$ compared with placebo. 5 Benefit was similar among patients with baseline LDL-C 50 to 70 mg/dL versus ${\ge}70$ mg/dL. 32 FOURIER (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk) and ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) enrolled patients with LDL-C ${\geq}70$ mg/dL and thus did not specifically assess out comes associated with adding PCSK9 inhibitor therapy among patients with LDL-C levels 55 to 70 mg/dL. 6,7 However, secondary analyses of both trials demonstrated better outcomes in patients with achieved LDL-C <50 mg/dL versus those with achieved LDL-C levels ${\tt\ge}50$ mg/dL, with monotonic relationships, suggesting better outcomes with progressively lower LDL-C even well below 50 mg/dL. 11,12 Rates of neurocognitive and muscle events, including hemorrhagic stroke, were not increased among patients who achieved very low LDL-C levels with PCSK9 inhibition. 11,12 Longer term follow-up studies support continued benefit and safety associated with achieving and maintaining very low LDL-C levels in secondary prevention with a PCSK9 inhibitor over several years. 33 The benefits of ezetimibe and PCSK9 inhibitors appear to be greater among higher risk patients with prior ACS and diabetes or more advanced coronary or polyvascular disease or elevated biomarkers. 20,34–41

5. Ezetimibe reduces LDL-C levels by $15\%$ to $25\%$ by blocking its absorption from the gastrointesti nal tract via the Niemann-Pick C1-Like 1 protein (NPC1L1). The IMPROVE IT trial studied the com bination of simvastatin $(40~\mathsf{m g})$ and ezetimibe (10 mg) (simvastatin-ezetimibe) to simvastatin (40 mg) and placebo (simvastatin monotherapy) in patients hospitalized with an ACS in the past 10 days. The median time from ACS to randomization was 5 days, and $34\%$ of patients were already on a statin at the time of the ACS event. The addition of ezetimibe reduced the relative risk of MACE by $6.4\%$ compared with placebo (hazard ratio, 0.936 $[95\%$ CI, 0.89-0.99]) over a median of 6 years’ fol low-up. Ezetimibe was well-tolerated without any clear imbalances in adverse events compared with placebo. 5

4.6. Beta-Blocker Therapy

|Recommendation for Beta-Blocker Therapy||| |---|---|---| || Referenced studies that support recommendation are summarized|| |||| |COR||| ||| 1. In patients with ACS without contraindications, early ( |

Synopsis

Beta blockers decrease myocardial oxygen demand by reducing the heart rate, blood pressure, and myocardial contractility. 1,3 The clinical benefit of beta blockers in pa tients with left ventricular ejection fraction (LVEF) ${<}40\%$ and stabilized HF is well established, including patients post-MI. 3–5 Most of the RCT data pertaining to early use of beta-blocker therapy in STEMI were conducted in the pre-reperfusion era. 3 No adequately powered RCTs have been done that examine the clinical benefit of beta block ers during hospitalization among patients exclusively with NSTE-ACS. Although most studies were conducted in pa tients with STEMI, early hospital initiation of beta-blocker therapy (within 24 hours) is recommended among most patients with ACS and without contraindications (eg, acute HF [Killip class II-IV], evidence of low cardiac output state or at risk for cardiogenic shock, PR interval ${\tt>}0.24$ milliseconds, second- or third-degree heart block without a cardiac pacemaker, severe bradycardia, active bron chospasm). 1,2,6 Patients with an initial contraindication to beta-blocker therapy on presentation can be reassessed after 24 hours and initiated on oral beta-blocker therapy if the initial contraindication has resolved. Further study is warranted to examine the benefit in those patients with NSTE-ACS. Although an open-label randomized trial has raised questions about the benefit of long-term betablocker therapy following hospital discharge in patients with ACS who have undergone coronary revasculariza tion and have preserved left ventricular (LV) function, 7 this area remains under study.

Recommendation-Specific Supportive Text

1. RCTs from both the pre-reperfusion era and in the early reperfusion era have shown that early initiation of beta-blocker therapy reduces the risk of reinfarction and ventricular arrhythmias among patients with STEMI. 1–3 The COMMIT (Clopidogrel and Metoprolol in Myocardial Infarction) trial included 45852 patients (approximately $50\%$ received fibrinolytic therapy and $7\%$ having NSTEACS) and showed that early initiation of high doses (ie, up to 15 mg intravenously then 200 mg orally daily) of metoprolol reduced the risk of reinfarction and ventricular fibrillation compared with placebo

but increased the risk of cardiogenic shock that occurred mainly during the first 24 hours. 1 In a small open-label trial of 801 patients with STEMI who underwent PPCI, carvedilol did not reduce MACE over 3 years, but the trial was underpow ered to detect a difference. 8 Overall, the weight of the evidence suggests that a low dose of oral beta blocker should be initiated in patients without contraindication early after diagnosis of ACS $(<\!24$ hours) with slow dose escalation as blood pressure and heart rate permit. Use should be discontinued in those with new or worsening HF symptoms or signs of cardiogenic shock. In hemodynamically stable patients with STEMI who do not have acute HF, intravenous beta blockers can be administered prior to reperfusion if there are ongoing symptoms or a clinical indication for administration. The weight of the evidence does not support the routine use of intravenous beta blockers prior to PPCI because of inconsistent results as to whether it has any favor able effect on infarct size or clinical outcomes. 9,10 The optimal duration of beta-blocker use remains unclear in patients with preserved LVEF. Although a randomized trial did not confirm long-term benefit from continued use of a beta blocker after hospital discharge in lower risk patients with preserved LV function who had undergone coronary revascular ization, 7 additional studies are ongoing in this space.

4.7. Renin-Angiotensin-Aldosterone System Inhibitors

|Recommendations for Renin-Angiotensin-Aldosterone System|||| |---|---|---|---| |Inhibitors|||| ||||| |COR|LOE|Recommendations|| ||||| ||| hypertension, diabetes mellitus, or STEMI with anterior location), an oral angiotensin-converting enzyme inhibitor (ACEi) or an angiotensin receptor blocker (ARB) is indicated to reduce || ||| hypertension, diabetes mellitus, or STEMI with anterior location), an oral angiotensin-converting enzyme inhibitor (ACEi) or an angiotensin receptor blocker (ARB) is indicated to reduce || ||| hypertension, diabetes mellitus, or STEMI with anterior location), an oral angiotensin-converting enzyme inhibitor (ACEi) or an angiotensin receptor blocker (ARB) is indicated to reduce || ||| hypertension, diabetes mellitus, or STEMI with anterior location), an oral angiotensin-converting enzyme inhibitor (ACEi) or an angiotensin receptor blocker (ARB) is indicated to reduce || ||B-R||| ||B-R| with HF symptoms and/or diabetes mellitus, a mineralocorticoidreceptor antagonist isindicated || ||B-R|2a|| | to reduce all-cause death and MACE.7 3. In patients with ACS who are not considered high risk, an oral ACEi or an ARB is reasonable to reduce MACE.4 |B-R|2a|| |||||

Synopsis

Oral ACE inhibitors reduce all-cause death and MACE in patients with STEMI or NSTEMI, particularly when associ ated with high-risk features (LVEF ${\leq}40\%$ , hypertension, diabetes mellitus, or STEMI with anterior location). 1–4,6 Even in AMI without high-risk features, use of an oral ACEi

confers a modest survival benefit. 4 Compared with ACEi, the benefits of an ARB in patients with AMI with HF or LV systolic dysfunction are similar. 5 Thus, in the absence of contraindications, either an oral ACEi or ARB should be initiated in appropriate patients with AMI. 5,8 In patients with AMI with LVEF ${\leq}40\%$ , and with HF symptoms and/ or diabetes mellitus, the addition of a mineralocorticoid receptor antagonist reduced all-cause death and MACE and should be given in the absence of advanced chronic kidney disease, hyperkalemia, or other contraindication.

In patients with symptomatic HF and reduced LVEF, sacubitril-valsartan has been demonstrated to be supe rior to an ACEi for reducing cardiovascular death or HF hospitalization; however, the trial excluded patients within 3 months of ACS. 9 In a trial of patients early after MI with LVEF ${\leq}40\%$ and/or pulmonary congestion, sacubitril-val sartan did not significantly reduce cardiovascular death or incident HF compared with an ACEi. Hypotensive events were more common with sacubitril-valsartan, but no other safety concerns were observed. Therefore, if treatment with sacubitril-valsartan for HF with reduced ejection fraction is planned, initiation of this combination agent instead of an ACEi or ARB early after MI appears safe. 10

Recommendation-Specific Supportive Text

1. Randomized controlled trials have demonstrated a reduction in all-cause death and MACE with the addition of an oral ACEi in patients with AMI with LVEF ${\leq}40\%^{1,3}$ and in patients with anterior STEMI. 2 An individual-patient meta-analysis of 98496 patients with AMI also showed a survival benefit with ACEi use, with the greatest absolute benefit in patients with hypertension, diabetes, and STEMI of anterior location. 4 In the VALIANT (Valsartan in Acute Myocardial Infarction) trial of patients with AMI with LV systolic dysfunction and/ or HF symptoms, the use of an ARB was statisti cally noninferior to an ACEi, and rates of all-cause death were similar between the 2 treatment arms. 5 Concomitant initiation of both an ACEi and ARB in patients with AMI should be avoided due to an increase in adverse events without added benefit compared with either drug alone. 5,8

2. In the EPHESUS (Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study) trial, the mineralocorticoid recep tor antagonist eplerenone reduced both all-cause death and MACE during a mean follow-up of 16 months in patients with AMI with LVEF ${\leq}40\%$ who also had symptoms of HF and/or diabetes melli tus. The use of evidence-based therapies for this population was relatively high, including $86\%$ use of ACEi or ARB and $75\%$ use of a beta blocker at enrollment. 7 Patients with advanced chronic kidney disease (serum creatinine ${\tt>}2.5$ mg/dL)

or hyperkalemia (serum potassium ${\tt>}5.0$ mmol/L) were excluded from enrollment. 7 In a trial of 1012 patients with acute STEMI and without a history of HF, the use of eplerenone reduced the primary end point compared with placebo, but the benefit was largely driven by a reduction in natriuretic peptides. 11 3. The ACE Inhibitor Myocardial Infarction Collaborative Group meta-analysis of 98496 patients with AMI reported a 30-day mortality rate of $7.1\%$ in AMI patients treated with an ACEi com pared with $7.6\%$ receiving placebo (proportional reduction, $7\%$ $[95\%$ CI, 2-11]; $P{=}0.004.$ ), and the benefit appeared to be irrespective of baseline risk. 4 The use of an ACEi also reduced nonfatal cardiac failure compared with placebo. 4

5. STEMI MANAGEMENT: REPERFUSION STRATEGIES

5.1. Regional Systems of STEMI Care

| Recommendation for Regional Systems of STEMI Care Referenced studies that support recommendation are summarized in ||| |---|---|---| |||| |COR|LOE|Recommendation| ||B-NR| 1. All communities should create and maintain regional systems of STEMI carenthatncoordinate prehospital and hospital-based STEMbcare processes with the | ||B-NR|goal of reducing total ischemic time and improving| |||survival in patients with STEMI.1-6 |

Synopsis

The goal of optimizing outcomes after STEMI depends not only on the efficient execution of STEMI care pro cesses but also on the seamless communication and co ordination of care among the teams caring for the patient. The goal of each community is therefore to ensure a co ordinated response to every patient with STEMI, regard less of physical location at presentation, to help minimize total ischemic time. The creation and maintenance of successful systems of STEMI care require detailed map ping of care for all possible routes by which a patient with STEMI could present for diagnosis and receive definitive reperfusion therapy at both PCI-capable and non–PCIcapable facilities, as well as access to cardiac surgical care and other advanced care modalities (Figure 6). The many stakeholders of regional systems of STEMI care (including hospitals, EMS companies, regional public health departments, and local governments) must ensure that all components of a STEMI system of care function in a coordinated way with no gaps in care processes to help optimize STEMI outcomes in the community.

Recommendation-Specific Supportive Text

1. The establishment of coordinated regional systems of STEMI care is associated with reduced time to

 Figure 6. Care System Pathway for Patients Experiencing Ischemic Symptoms Suggestive of ACS. Systems of STEMI care, and the most common routes by which patients present for diagnosis and definitive reperfusion therapy for STEMI. Best clinical practice consists of patients calling 9-1-1 (or other emergency services) to activate EMS; EMS obtaining a prehospital ECG, activating the cardiac catheterization laboratory from the field for suspected STEMIs, and transporting the patient to the nearest PCI center when possible; and achieving a system goal of FMC-to-device time within 90 minutes. Colors correspond to Class of Recommendation in Table 2. \*Patients with chest tightness or other symptoms indicative of a heart attack. ACS indicates acute coronary syndromes; ED, emergency department; EMS, emergency medical services; FMC, first medical contact; PCI, percutaneous coronary intervention; PPCI, primary percutaneous coronary intervention; and STEMI, ST-segment elevation myocardial infarction.

reperfusion and increased survival in STEMI in several pre- versus postimplementation comparison studies throughout the world. 1–6 Over the past 15 years, con siderable gains have been made in reducing FMC to reperfusion times in patients with STEMI and these

improvements in reperfusion times have been asso ciated with improved outcomes. 5,7 Unfortunately, recent declines have been reported in the rates of achieving established STEMI performance mea sures, 8 in part due to the COVID-19 pandemic and

related challenges in ensuring adequate resourc ing and staffing of EMS agencies and hospitals. Therefore, all communities should continue to estab lish, reinvigorate, and maintain regional systems of STEMI care to improve outcomes of patients with STEMI globally. The collection of high-quality data at every stage of care is an inseparable component of a STEMI system of care. Successful STEMI systems have robust mechanisms for (1) educating the pub lic of the need to immediately call 9-1-1 (or other appropriate local emergency services) for ischemic symptoms and not driving themselves to the nearest hospital; (2) data collection that balances the need for adequate data capture without introducing data overburden; (3) data sharing within hospital depart ments (eg, ED and cardiology) or between hospitals and EMS agencies; and (4) meetings to review and discuss shared data at local and system levels to drive process improvement.

5.2. Reperfusion at PCI-Capable Hospitals

5.2.1. PPCI in STEMI

| Recommendations for PPCI in STEMI Referenced studies that support recommendations are summarized in the Evidence Table. ||| |---|---|---| |COR|LOE|Recommendations| |||1. In patients with STEMI presenting |

\*Reproduced or †modified from the “2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization.” 18

Synopsis

Timely PPCI confers improved survival compared with fibri nolytic therapy as primary reperfusion therapy for patients with STEMI. 6,7 Systems of care designed to reduce the time to PPCI for patients with STEMI have been consequential in reducing risk of early death. 19,20 The goal is to provide

PPCI as soon as possible after the diagnosis of STEMI is made with first device activation within 90 minutes from FMC among walk-in and EMS-transported patients and 120 minutes for transfer patients from non–PCI-capable facilities. 1–7 The benefit of PPCI begins to diminish for those ${>}12$ hours from symptom onset, but there appears to be continued benefit for PPCI through approximately 24 hours. 12,13 In stable asymptomatic patients with an occlud ed artery ${>}48$ hours after symptom onset, routine PCI has not been shown to be beneficial in the absence of ongoing ischemia; the relative utility of routine PCI for asymptomatic patients with STEMI between 24 to 48 hours from symp tom onset is less rigorously tested. 14,15 However, coronary revascularization should be considered for patients with late presentations with continued signs and symptoms of ischemia, including cardiogenic shock, acute severe HF, persistent angina, and life-threatening arrhythmias.

Recommendation-Specific Supportive Text

1. PPCI is the recommended reperfusion therapy in patients with STEMI and ischemic symptoms when performed ≤ 90 minutes (FMC–to–first-device activation) or ${\le}120$ minutes in transfer patients to improve survival. 1–7 The success of PPCI in achiev ing these goals was facilitated by the introduction in 2006 of the AHA’s Mission: Lifeline programs involving EMS and clinicians (eg, emergency medi cine, cardiology, nursing) with practiced drill-down programs and regionalization of care 21 that have improved myocardial salvage, as well as reduced risk of death and adverse outcomes. 4,22,23 PPCI is superior to fibrinolytic therapy, which is used when the patient is in a non–PCI-capable hospital and transfer time to a PCI-capable hospital is anticipated to be ${>}120$ minutes. Compared with fibrinolytic therapy with a similar treatment delay, PPCI offers higher rates of infarct-related artery patency, and restoring TIMI 3 epicardial flow grade, as well as lower rates of recur rent ischemia, reinfarction, emergency repeat revas cularization procedures, intracranial hemorrhage, and death. 6,7 Radial access for PPCI has further reduced death, decreased access site bleeding, decreased the need for transfusion, and reduced acute kidney injury when compared with femoral access (Section 7.1, “Vascular Access Approach for PCI”). 24,25

2. In the SHOCK (Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock) trial, 9 reported in 1999, patients with AMI and cardiogenic shock were randomized to medical therapy or emer gency revascularization. Among the patients ran domized to revascularization, $64\%$ of patients were referred for PCI and $36\%$ for CABG surgery. The median time from randomization to revasculariza tion was 0.9 hours for PCI and 2.7 hours for CABG surgery. Despite lack of a significant difference in

the primary endpoint of mortality at 30 days, emer gency revascularization with either PCI or CABG surgery reduced mortality at 6 months, 9 and the mortality rate benefit was maintained through 1 and 6 years. 26,27 In an observational analysis from the FITT-STEMI (Feedback Intervention and Treatment Times in ST-Elevation Myocardial Infarction) trial, for every 10-minute delay in PPCI after 60 minutes from FMC, there were an additional 3 to 4 deaths per 100 with ${\mathrm{>}80\%}$ mortality beyond 6 hours of delay from FMC for patients with cardiogenic shock. 8 Therefore, it is recommended that PPCI should be performed in patients with STEMI and cardiogenic shock as soon as possible, ideally within 90 minutes, to reduce the mortality rate. Observational studies suggest that emergency CABG surgery remains a treatment option in patients with cardiogenic shock who are not amenable to primary reperfusion with PCI 10,11 or when PCI is not successful. 11,28

3. The benefit of PCI for asymptomatic patients pre senting 12 to 24 hours after symptom onset is not well studied. Small randomized trials of patients 12 to 48 hours after symptom onset in STEMI have demonstrated that PPCI reduces infarct size and improves the LVEF. 12,14 These findings are further supported by observational data. 13,15

4. No dedicated trials have been done that examine the benefit of PPCI in patients with STEMI presenting late ${\tt>}24$ hours after symptom onset who have clini cal evidence of ongoing ischemia, acute severe HF, or life-threatening arrhythmias. Observational data and small trials suggest that PCI in patients with STEMI with delayed presentations is reasonable and is associated with improved outcomes. 12,14,15

5. PCI is not recommended for an occluded infarctrelated artery if the patient is asymptomatic and has a completed infarct. MACE outcomes were similar in those with an occluded infarct-related artery versus those who underwent PCI 3 to 28 days after an MI (Occluded Artery Trial [OAT]) 16 and results were no different at 7 years follow-up. 29 Similar findings were noted in the DECOPI (Desobstruction Coronaire en Post-Infarctus) trial, which enrolled patients with an occluded artery and Q waves on the ECG present ing 2 to 15 days after symptom onset. 17

Synopsis

Trials that evaluated the efficacy and safety of CABG surgery in STEMI are limited. 4 When PCI is not possible for anatomic reasons or in the presence of complex dis ease, CABG surgery can be performed as the primary reperfusion strategy. After successful reperfusion of the infarct-related artery, CABG surgery can also be impor tant when managing patients with more extensive nonin farct-related artery disease (Section 7.4.1, “Management of Multivessel CAD in STEMI”). The appropriate timing of CABG surgery in patients with STEMI should be de termined on an individual basis, taking into consideration the hemodynamic stability of the patient, the presence of ongoing ischemia, and extent of myocardium at risk. Af ter failed PPCI, emergency CABG surgery is not recom mended in the absence of a large area of myocardium at risk or if surgical targets are poor and if surgery may be associated with an increased risk of death and adverse cardiovascular outcomes compared with nonsurgical management. 5 For recommendations regarding CABG surgery in patients presenting with cardiogenic shock or mechanical complications, please refer to Section 8.1, “Revascularization in ACS With Cardiogenic Shock” and Section 9.1, “Mechanical Complications.”

Recommendation-Specific Supportive Text

1. No RCTs have been done that compare PPCI with surgical revascularization in the setting of STEMI. For patients with STEMI who are hemodynamically stable with anatomy of the infarct-related artery that is not amenable to PPCI, or if PPCI is unsuccessful, CABG surgery can be useful if there is a large area of myocardium at risk. In such patients, particularly in the presence of ongoing ischemia or if a large area of myocardium is at risk, CABG surgery may be effectively performed as a primary reperfusion strat egy or after PPCI. 1,2 Despite an increase in the acu ity of presentation and the burden of comorbidities, the in-hospital mortality rate after CABG surgery in patients with STEMI continues to decrease. 1,4

5.3. Reperfusion at Non–PCI-Capable Hospitals

5.2.2. Urgent CABG Surgery

|Recommendation for Urgent CABG Surgery||| |---|---|---| |||| |COR|Recommendation|Recommendation| |2a|B-NR| 1. In patients with STEMI in whom PCl is not feasible or successful, with a large area of myocardium at risk, emergency or urgent CABG surgery can be | |2a|B-NR|| ||B-NR|effective to improve clinical outcomes.*12|

\*Modified from the “2021 ACC/AHA/SCAI Guideline for Coronary Artery Re vascularization.” 3

||| Recommendations for Reperfusion at Non-PCl-Capable Hospitals Referenced studies that support recommendations are summarized || |---|---|---|---| |COR|LOE|Recommendations|| ||| 1. In patients with STEMl and an estimated time from FMC to device activation of ≤120 minutes or those with a contraindication to fibrinolytic || ||| from FMC to device activation of ≤120 minutes or those with a contraindication to fibrinolytic therapy, transfer to a PCl-capable hospital for PPCI is recommended to reduce MACE.1-3 || ||||| ||| In patients with STEMI and symptom onset of ||

|(Continued)|||| |---|---|---|---| |(Continued)|||| |COR|B-NR|Recommendations|| ||B-NR| 3.1 In patients with STEMl and symptom onset of 12 to 24 hours, transfer to a PCl-capable12 to 24 hours, transfer to a PCl-capable hospital for PPCl is reasonable to reducehospital for PPCl is reasonable to reduce infarct size and MACE.11.12 || |3:Harm|B-NR| 4. In patients with only ST-segment depres- sion, except when true posterior STEMI is || |3:Harm|B-R|suspected, fibrinolytic therapy should not be|| |3:Harm|B-R|administered due to risk of hemorrhagic stroke|| |3:Harm||||

Synopsis

A large proportion of patients globally live ${>}1$ hour driving time to a PCI-capable hospital. 14–17 At non–PCI-capable hospitals, transfer for PPCI is recommended if device ac tivation can be reasonably predicted to occur in ${<}2$ hours from FMC. If this cannot be achieved and symptoms have been present ${<}12$ hours, fibrinolytic therapy is recom mended to reduce the risk of recurrent MACE. Patients with STEMI who present to a non–PCI-capable facility $\geq\!12$ hours after onset of symptoms should be trans ferred to a PCI-capable facility when possible. However, if the patient has associated hemodynamic instability or a large infarct territory at risk, they are at very high risk for morbidity and death, and in this situation where timely PPCI is not possible, the benefits of fibrinolytic adminis tration likely outweigh the benefit of prolonged transfer for PPCI.

Recommendation-Specific Supportive Text

1. PPCI is recommended to reduce the risk of MACE when FMC to PPCI can be achieved within 120 minutes. A patient who presents to a non–PCIcapable hospital with STEMI should be transferred to a PCI-capable hospital when this intervention can be accomplished within 120 minutes. 1,2,18 System delays related to transfer are frequently underestimated, and a case-by-case approach should be calculated for each patient with STEMI prior to transfer for PPCI. 19–21

2. The use of fibrinolytic therapy in STEMI in the United States is driven by patients who are unable to receive timely PPCI $(<\!120$ minutes FMC to device activa tion). Numerous RCTs and meta-analyses have demonstrated superiority to PPCI over fibrinolytic therapy. However, the benefits of PPCI versus fibri nolytic therapy diminish with increasing PCI-related time delay such that after 120 minutes, the benefits are no longer as clear when compared with more timely fibrinolytic therapy administration. 19 In these patients, when timely PPCI cannot be performed, meta-analyses of RCTs and observational studies show statistically similar morbidity and mortality

rates for a pharmaco-invasive approach (eg, fibrino lytic therapy followed by PCI within 2 to 24 hours) when a patient does not have timely access to PPCI. 4,5 The STREAM (Strategic Reperfusion Early After Myocardial Infarction) trial, which randomized 1892 early presenters (symptoms ${\vartriangle}3$ hours) with STEMI unable to receive PCI within 1 hour of FMC, found that both a 30-day composite (eg, death, shock, CHF, or reinfarction) and 1-year mortality rates were similar for prehospital fibrinolysis versus transfer for PPCI. 10,22

3. Small studies suggest that PPCI continues to offer clinical benefit in patients 12 to 24 hours after symp toms onset; therefore, transfer to a PCI-capable hos pital is reasonable. 11,12 Late presenters with STEMI who have associated hemodynamic instability or large infarct size are at very high risk for acute dete rioration and long-term morbidity. In this situation, fibrinolytic administration may outweigh potential risks when timely PPCI is not possible. Fibrinolysis in this setting should be followed by transfer to a PCI-capable center as soon as feasible.

4. There is no benefit of fibrinolysis and there is potential harm (eg, hemorrhagic stroke and major noncerebral bleeding) in administering fibrinolytic therapy to patients who present with symptoms concerning for ACS without ST-segment elevation or suspected true posterior STEMI. 13

5.3.1. Timing and Choice of Agent for Fibrinolytic Therapy

Synopsis

PPCI remains the reperfusion modality of choice when it can be rapidly achieved in a patient with STEMI. In in stances where this is not possible or cannot be achieved in a timely manner, the benefits of coronary reperfusion with fibrinolytic therapy in patients with STEMI are well established, with a time-dependent reduction in both mortality and morbidity rates during the initial 12 hours after symptom onset, especially in those who present ear ly after symptom onset with low bleeding risk and large anterior infarctions. 1–7 The benefit of fibrinolytic therapy in patients who present ${>}12$ hours after symptom on set has not been established, 8–10 although consideration should be given to administering a fibrinolytic agent in symptomatic patients presenting ${>}12$ hours after symp tom onset of STEMI with a large area of myocardium at risk or hemodynamic instability, if PCI is unavailable. Fibrin-specific fibrinolytic therapies are preferred over non–fibrin-specific agents due to superior patency rates and less immunogenicity (Table 13). 11–16 Tenecteplase is a genetically engineered version of alteplase with higher specificity for fibrin. In a large randomized trial of patients with AMI, tenecteplase and alteplase were equivalent for 30-day mortality rates, but tenecteplase was associ ated with reduced noncerebral bleeding. 17 Reteplase (re

Table 13. Fibrin-Specific Fibrinolytic Agents for STEMI

|Fibrinolytic Agent|Dose| |---|---| |Tenecteplase (TNK-tPA)|Single IV weight-based bolus*| |Reteplase (rPA)|Two 10-unit IV boluses given 30 min apart| ||(administered over 2 min)| |Alteplase (tPA)|90-min weight-based infusiont|

\*30 mg for weight ${<\!60~\mathsf{k g}}$ ; 35 mg for 60-69 kg; 40 mg for 70-79 kg; 45 mg for 80-89 kg; and 50 mg for ≥ 90 kg.

†Adults ≥ 67 kg: 100-mg total dosage administered as a 15-mg IV bolus, fol lowed by 50-mg IV infused over 30 min, and then 35-mg IV infused over the next 60 min. Adults <67 kg: 15-mg IV bolus, followed by $0.75\;\mathsf{m g}/\mathsf{k g}\;|$ V (not to exceed 50 mg) infused over 30 min, and then 0.5 mg/kg IV (not to exceed 35 mg) over the next 60 min.

rPA indicates reteplase plasminogen activator; TNK-tPA, tenecteplase tissuetype plasminogen activator; and tPA, tissue-type plasminogen activator.

combinant plasminogen activator) has not been shown to improve survival compared with alteplase in patients with MI, but its convenient bolus dosing allows for greater ease of use. 18 Adjunctive antiplatelet and/or anticoagu lant therapies are indicated, regardless of the choice of fibrinolytic agent (Sections 4.3.2., “Oral P2Y12 Inhibitors During Hospitalization,” and 4.4, “Parenteral Anticoagula tion”). Absolute and relative contraindications for fibrino lytic therapy are listed in Table 14.

Patients should be transferred to a PCI-capable hospital after initiation of fibrinolytic therapy for routine coronary angiography (Section 5.3.2., “Coronary Angiog raphy and PCI After Fibrinolytic Therapy”). Signs of failed reperfusion are discussed in Section 5.3.2.

5.3.2. Coronary Angiography and PCI After Fibrinolytic Therapy

|Recommendations for Coronary Angiography and PCl After Fibrinolytic|||| |---|---|---|---| ||||| |COR|LOE|Recommendations|| ||| 1. In patients with STEMl, transfer to a PCl-capable center immediately after fibinolytic therapy is recommended.1-5 || ||B-R| 2. In patients with STEMI with suspected failed reperfusion after fibrinolytic therapy, || ||B-R| failed reperfusion after fibrinolytic therapy, immediate angiography with rescue PCi is immediate angiography with rescue PCi is recommended toreduce theriskof deathorrecommended toreduce theriskof deathor recurrent Ml.*6-9 || ||B-R||| ||B-R| 3. In patients with STEMI treated with fibrino- lytic therapy, early angiography between 2 and 24 hours with the intent to perform PCl is recommended to reduce the rates of death Or MI.*1-5,10,11 || ||B-R|||

\*Modified from the “2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization.” 12

Synopsis

Failure of reperfusion and risk of reocclusion after suc cessful fibrinolytic therapy are important limitations of fibrinolytic therapy. For this reason, all patients receiving

Table 14. Absolute and Relative Contraindications for Fibri nolytic Therapy in STEMI\*

|Absolute Contraindications| |---| |Any prior ICH| |Known structural cerebral vascular lesion (eg, arteriovenous malformation)| |Known malignant intracranial neoplasm (primary or metastatic)| |Ischemic stroke within 3 mo except acute ischemic stroket| |Suspected aortic dissection| |Active bleeding or bleeding diathesis (excluding menses)| |Significant closed-head or facial trauma within 3 mo| |Intracranial or intraspinal surgery within 2 mo| | Severe uncontrolled hypertension (unresponsive to therapy) (SBP >180 mm Hg or DBP >110 mm Hg) | |Relative Contraindications| |History of chronic, severe, poorly controlled hypertension| | Significant hypertension on presentation (SBP >180 mm Hg or DBP >110 mm Hg) | |History of prior ischemic stroke >3 mo| |Dementia| |Known intracranial pathology not covered in absolute contraindications| |Traumatic or prolonged (>10 min) CPR| |Major surgery (|

\*Viewed as advisory for clinical decision-making and may not be all-inclusive or definitive. †Acute ischemic stroke within 4.5 h of onset. CPR indicates cardiopulmonary resuscitation; DBP; diastolic blood pressure; ICH, intracranial hemorrhage; SBP, systolic blood pressure; and STEMI, ST-seg ment elevation myocardial infarction.

fibrinolytic therapy should be transferred to a PCI-capa ble hospital to facilitate immediate or early catheteriza tion depending on the clinical circumstances. Hospitals should have transfer protocols in place to allow for a seamless transfer to the PCI-capable facility as soon as it is safe to do so. A detailed assessment of clinical status is critical to determine the timing of angiography. A lack of improvement in ischemic symptoms, persistent ST-segment elevation $(<\!50\%$ resolution of ST-segment elevation in the anterior leads or ${<}70\%$ in inferior leads [measured either from the lead with maximal baseline ST elevation or as the sum of ST-segment deviation across leads]), 13 or hemodynamic or electrical instability can in dicate incomplete reperfusion by fibrinolytic therapy. 14 When there are signs of failed reperfusion, patients should undergo immediate coronary angiography and rescue PCI. For the remaining patients, routine coronary angiography within 2 to 24 hours after fibrinolytic ther apy with coronary revascularization as needed is recom mended.

Recommendation-Specific Supportive Text

1. Numerous clinical trials have evaluated a strategy of early coronary angiography with possible PCI after fibrinolytic therapy. This strategy of immediate transfer and angiography has been associated with lower rates of recurrent ischemic events as com pared with usual care. 1–5 Regardless of the timing of angiography, immediate transfer enables earlier access to specialized centers, providing critical care services and on-site catheterization laboratory teams that can facilitate clinical assessments to determine the likelihood of reperfusion and enable earlier angiography for the unstable patient.

2. Rescue PCI is associated with improved outcomes in patients with clinical signs of failed reperfu sion after fibrinolytic therapy. Several trials have demonstrated a trend toward lower mortality and significantly lower rates of recurrent MI and HF when rescue PCI is performed for failed fibrinoly sis. 6,7 The REACT (Rapid Early Action for Coronary Treatment) trial 6 enrolled 427 patients with failed reperfusion at 90 minutes after fibrinolysis to 1 of 3 treatment arms, including rescue PCI, conserva tive care, or repeat fibrinolytic therapy. Rescue PCI significantly reduced the composite primary end point of death, reinfarction, stroke, or severe HF at 6 months compared with either conservative care or repeat fibrinolytic therapy. Meta-analyses also support lower rates of death or reinfarction when rescue PCI is performed in this setting. 8,9 Minor and major bleeding and rates of stroke were sig nificantly higher with rescue PCI. 6–8 These studies were performed in the era of femoral artery access, with fewer options for antiplatelet and anticoagu lant therapy. The use of radial artery access 15 and the elimination of the routine use of glycoprotein IIb/IIIa inhibitors has reduced bleeding. For this reason, the balance of benefit from rescue PCI out weighs the risks for most patients with evidence of failed reperfusion after fibrinolysis.

3. Routine early angiography with the intent to perform PCI after fibrinolysis reduces MACE in comparison to usual care (delayed coronary angiography and/ or an ischemia-guided strategy of revasculariza tion). 1–5,11,16 In these studies, ${\mathrm{>}80\%}$ of patients who were transferred underwent PCI to treat a sig nificant residual stenosis or suboptimal flow of the infarct-related artery. Meta-analyses of the RCTs showed a reduction in the combined endpoint of death or reinfarction with an early invasive approach after fibrinolytic therapy. 10,17,18 In a network metaanalysis evaluating clinical outcomes with different modes of reperfusion for STEMI, a pharmaco-inva sive strategy (defined as an interval between lysis and PCI ${\geq}2$ hours) was associated with a $21\%$ reduction in the mortality rate when compared

with a strategy of fibrinolysis alone. 18 Furthermore, contemporary registries have shown an associa tion between a pharmaco-invasive approach and improved outcomes compared with PPCI when transfer times are long. 19 The optimal timing of angiography and PCI after fibrinolytic therapy has not been clearly defined but a similar benefit in ischemic endpoints is evident across the spectrum of times included in the clinical trials. 17,20 Although earlier studies raised concerns for increased bleed ing with very early catheterization (mean time, 2.2 hours), 21 more contemporary data suggest similar rates of bleeding even if cardiac catheterization is performed very early after fibrinolytic therapy. 17,20

6. NSTE-ACS: ROUTINE INVASIVE OR SELECTIVE INVASIVE INITIAL APPROACH

6.1. Rationale and Timing for a Routine Invasive or Selective Invasive Approach

|| Recommendations for Rationale and Timing for a Routine Invasive or||| |---|---|---|---| |Selective Invasive Approach|||| || Referenced studies that support recommendations are summarized in||| |the Evidence Table.|the Evidence Table.|the Evidence Table.|| |COR|LOE|Recommendations|| |Routine Invasive Versus Selective Invasive Strategy|||| ||| 1. In patients with NSTE-ACS who are at intermediate or high risk of ischemic events and are appropriate candidates for revascularization, an invasive approach with the intent to proceed with revascularization is recommended during hospitalization to reduce MACE.*1-6 || ||||| ||| In patients with NSTE-ACS who are at low risk of ischemic events, either a routine invasive or selective invasive approach is recommended to help identify those who may require || ||||| ||Timing of Coronary Angiography for Those in Whom an Invasive||| ||C-LD||| ||C-LD| In patients with NSTE-ACS who have refractory angina or hemodynamic or electrical instability, an immediate invasive strategy with intent to perform revascularization is indicated to reduce MACE.8-11 4. In patients with NSTE-ACS who are at high risk+ of ischemic events, it is reasonable to choose an early invasive strategy (within 24 hours) to reduce MACE.+8,9,11,12 || | 2a 2a |B-R| In patients with NSTE-ACS who are not at high risk and are intended for an invasive strategy, it is reasonable to perform angiography before hospital discharge to reduce MACE.*:1 ||

\*Reproduced or †modified from the “2021 ACC/AHA/SCAI Guideline for Coronary Artery Re vascularization.” 7 ‡Predictors of risk are outlined in Figure 8.

Synopsis

A routine invasive approach refers to a strategy of performing coronary angiography with the intent to

perform coronary revascularization by PCI or CABG (as appropriate) in patients with NSTE-ACS. This approach provides important prognostic information, including de lineating the extent and severity of CAD. Several RCTs have demonstrated that a routine invasive approach in patients with NSTE-ACS reduces the risk of MACE when compared with a selective invasive approach. 1–3 Notably, these strategy trials were conducted in an era prior to the availability of hs-cTn assays, routine use of radial approach for coronary angiography, newer generation drug-eluting stents, and contemporary ev idence-based antiplatelet therapies. Patients who are at prohibitively high risk from angiography or who have known coronary anatomy or preferences that preclude revascularization (PCI or CABG) may be managed non invasively. 13 In addition, some low-risk patients, particu larly those who have normal cardiac biomarkers and in whom a diagnosis of an ACS is questioned, should be considered for a “selective invasive” approach that includes further noninvasive risk stratification prior to consideration of coronary angiography, because they derive less benefit from a routine invasive approach. 4,7,13 These low-risk patients should still undergo noninva sive stress testing or coronary CT angiography prior to

hospital discharge. Patients with higher risk findings on noninvasive testing or who have recurrent ischemic symptoms should be referred for invasive coronary an giography prior to hospital discharge in the absence of contraindication (Figure 7).

Recommendation-Specific Supportive Text

1. In patients with NSTE-ACS, a routine invasive approach improves clinical outcomes, including lower rates of recurrent MI and recurrent isch emia, compared with a selective invasive approach that involves further noninvasive risk stratification prior to consideration of angiography. 1–3 In a col laborative meta-analysis of RCTs, a routine inva sive approach reduced death or MI by $18\%$ (OR, 0.82 $[95\%$ CI, 0.72-0.93]), including a $25\%$ reduc tion in MI (OR, 0.75 $[95\%$ CI, 0.65-0.88]) when compared with a selective invasive approach. 5 The benefit was more apparent in higher risk patients with elevated biomarkers. 4 The studies that estab lished the benefit of a routine invasive approach were conducted in the late 1990s and early 2000s, and it is unknown whether contemporary

 Figure 7. Selection of a Routine Invasive Versus Selected Invasive Strategy in Patients With NSTE-ACS. Colors correspond to Class of Recommendation in Table 2. \*AHA Scientific Statement on MINOCA. 17 CABG indicates coronary artery bypass grafting; CCTA, cardiac CT angiography; MINOCA, myocardial infarction with nonobstructive coronary artery disease; NSTE-ACS, non–STsegment elevation acute coronary syndromes; and PCI, percutaneous coronary intervention.

therapies and advances in interventional methods would yield different results. Similarly, elevated cardiac biomarkers (CK-MB and older genera tion troponin assays) identify those who benefit more from a routine invasive strategy; however, it remains unknown whether hs-cTn assays that detect smaller degrees of myonecrosis are as use ful for identifying those who benefit from routine coronary angiography. Although women are less likely to have obstructive coronary disease at angi ography, they derive as much benefit from a rou tine invasive approach in the presence of similar risk predictors. 4 The GRACE 2.0 risk calculator and TIMI Risk Score for unstable angina/NSTEMI may help identify patients at increased risk of MACE who benefit more from a routine invasive approach (Table 5). 1 Relative contraindications to coronary angiography that merit further consider ation of the relative risks and benefits of a routine invasive approach are outlined in Table 15.

2. Although some trials have demonstrated a reduc tion in MACE with a routine invasive approach in NSTE-ACS, 1–3 others have not demonstrated a significant benefit when compared with a selective approach that involves further risk stratification. 4,7 Although a pooled analysis of 3 randomized tri als suggested that the benefit of a routine invasive approach was independent of baseline risk, 6 other meta-analyses across studies have suggested that lower risk patients may derive less bene fit. 4,5,14 In addition, some low-risk patients, particu larly those who have normal cardiac biomarkers in whom a diagnosis of an ACS is suspect, may have improved outcomes with a selective invasive approach. 4,5 These patients should preferentially undergo noninvasive stress testing or coronary CT angiography prior to hospital discharge to help determine the need for coronary angiography; however, patients with suspected ongoing isch emic symptoms should be considered for coronary angiography.

Table 15. Relative Contraindications for a Routine Invasive Approach in ACS

|High risk for bleeding on DAPT| |---| |Severe thrombocytopenia (platelet count |

ACS indicates acute coronary syndromes; CABG, coronary artery bypass graft ing; DAPT, dual antiplatelet therapy; and PCI, percutaneous coronary intervention.

3. Patients with NSTE-ACS who are unstable (eg, refractory or recurrent angina [despite optimal medical therapy, hemodynamic or electrical instabil ity, acute pulmonary edema or HF, worsening mitral regurgitation]) have been largely excluded from RCTs. Despite a relative paucity of clinical trial data, these patients are at heightened risk of adverse outcomes, and an immediate invasive strategy $\scriptscriptstyle(<\!2$ hours from hospital admission) with intention to perform revascularization is recommended. 8,15 If patients with ACS and unstable features are at a non–PCI-capable hospital, they should be imme diately transferred to a PCI-capable facility with a goal of immediate angiography. Clinical features that support immediate coronary angiography with intent to revascularize are listed in Figure 8.

4. For patients with NSTE-ACS for whom the deci sion has been made to proceed with coronary angiography, the benefit of an early invasive ver sus a delayed invasive approach is unclear. 8,9,11,12 In the TIMACS (Timing of Intervention in Acute Coronary Syndromes) trial, 11 patients were enrolled within 24 hours of symptoms and randomized to early angiography within 24 hours versus delayed angiography ${\geq}36$ hours from time of randomization. In the VERDICT (Very Early vs Deferred Invasive Evaluation Using Computerized Tomography) trial, 12 patients were randomized to early angiog raphy within 12 hours versus delayed between 48 to 72 hours from time of diagnosis. Both studies reported no significant difference in MACE between an earlier versus delayed invasive approach in the overall study populations, but there was signal toward a reduction in MACE with an earlier invasive approach in the higher risk patients with a GRACE risk score >140. 11,12 In a meta-analysis of RCTs that compared an early versus delayed approach, a mortality benefit was not seen with earlier angiog raphy. However, factors that favored an earlier inva sive approach included a GRACE risk score ${>}140$ , diabetes, age ${>}75$ years, and elevated cardiac bio markers (although formal tests for interaction were not significant). 8 Although not evaluated in RCTs, a continuing steep rise in cardiac biomarkers, likely due to ongoing ischemia and myonecrosis despite optimized medical therapy, may also favor earlier coronary angiography.

5. In intermediate- or low-risk patients for whom angiography is planned in NSTE-ACS, timing does not appear to be critical, and a delayed invasive strategy within 48 to 72 hours does not appear to increase future risk of MACE. 8,10–12,15 Randomized trial data have not demonstrated an overall signifi cant difference in death or MI between an earlier versus delayed invasive approach in nonselected patients with NSTEMI. 8,11,12,16

 Figure 8. Selection and Timing of an Invasive Strategy in NSTE-ACS.

Figure 8 summarizes the recommendations in the 2025 ACS Guideline for a routine or selective invasive approach in NSTE-ACS. It is not meant to encompass every patient scenario or situation, and clinicians are encouraged to use a Heart Team approach when care decisions are unclear and to see the accompanying supportive text for each recommendation. Colors correspond to Class of Recommendation in Table 2. GRACE indicates Global Registry of Acute Coronary Events; HF, heart failure; NSTE-ACS, non–ST-segment elevation acute coronary syndromes; Tn, troponin; TIMI, Thrombolysis in Myocardial Infarction; VF, ventricular fibrillation; and VT, ventricular tachycardia. Adapted with permission from Lawton et al. 18 Copyright 2022 American Heart Association, Inc., and American College of Cardiology Foundation.

7. CATHETERIZATION LABORATORY CONSIDERATIONS IN ACS

7.1. Vascular Access Approach for PCI

Recommendation for Vascular Access Approach for PCI Referenced studies that support recommendation are summarized in the Evidence Table .

|COR|LOE|Recommendation|Recommendation| |---|---|---|---| ||||| |||| approach is preferred to a femoral approach to reduce bleeding, vascular complications, and death.*1-6 |

\*Modified from the “2021 ACC/AHA/SCAI Guideline for Coronary Artery Re vascularization.” 7

Synopsis

The radial artery has become the preferred vascular ac cess site for patients undergoing cardiac catheterization and PCI. 8,9 Transradial access is associated with lower mortality, bleeding, and vascular complications in pa tients treated for ACS. 5 In addition, patients prefer radial access because it allows earlier ambulation and causes less discomfort than femoral access. 9 A caveat is most trials comparing radial versus femoral access had very

low crossover rates because they required operators with expertise in radial access. 3 The choice of radial access has to be weighed against the possibility that the radial artery could be used as a bypass conduit for CABG surgery. 10 In sites where surgeons routinely utilize the radial artery as a bypass conduit, consideration should be given on the choice of vascular access and future use of radial artery for the cardiovascular surgical team. Although the radial artery is the most widely studied wrist access site, the use of alternative sites in the upper extremity, includ ing the ulnar and distal radial arteries have yielded similar outcomes. 11,12 Transfemoral access, preferably with the use of ultrasound guidance, should be considered in pa tients in whom temporary MCS is planned and is the de fault alternative access site among patients in whom the radial artery cannot be used due to clinical, anatomical, or technical reasons. 13

Recommendation-Specific Supportive Text

1. RCTs have consistently demonstrated the ben efit of radial access in comparison with femoral access among patients treated for ACS. A metaanalysis using individual patient data from 7 highquality RCTs ( $48.6\%$ with NSTE-ACS; $46.2\%$ with

STEMI) demonstrated that radial access was inde pendently associated with a significant $24\%$ and $51\%$ relative risk reduction of all-cause death and major bleeding, respectively, when compared with femoral access. 3 The magnitude of the mortal ity benefit was greater among patients with lower baseline hemoglobin levels. The benefit of radial access toward reducing bleeding was driven by a significant reduction in access-site bleeding. Vascular complications were significantly reduced by $62\%$ . The MATRIX trial 6 demonstrated a sig nificantly lower rate of the coprimary endpoints of MACE and net adverse clinical events (composites of death, MI, and stroke at 30 days, and MACE plus non-CABG major bleeding) among patients with ACS randomized to the transradial approach com pared with the transfemoral approach. This is con sistent with prior meta-analyses that have reported lower mortality and bleeding with radial access in patients with ACS. 4,14 The SAFARI-STEMI (Safety and Efficacy of Femoral Access versus Radial for Primary Percutaneous Intervention in ST-Elevation Myocardial Infarction) trial showed no difference in 30-day mortality rates between radial and femo ral access; however, the trial stopped early and therefore was underpowered to detect a mortality benefit. 15

7.2. Use of Aspiration Thrombectomy

|Recommendation for Use of Aspiration Thrombectomy|||| |---|---|---|---| ||||| |COR|LOE|Recommendation|| | 3:NO benefit | | 1. Among patients with STEMI undergoing PPCI, manual aspiration thrombectomy should not be performed routinely prior to PCl given lack of || | 3:NO benefit | |||

\*Modified from the “2021 ACC/AHA/SCAI Guideline for Coronary Artery Re vascularization.” 5

Synopsis

Despite restoration of coronary patency, suboptimal myo cardial perfusion resulting from distal embolization or mi crovascular obstruction is frequent and is associated with larger infarct size, impairment of LV function, and excess mortality rates. 6,7 Removing coronary artery thrombus pri or to balloon angioplasty, stent deployment, or both is an intuitive adjunct to PPCI that may yield putative clinical benefits. Routine manual thrombus aspiration performed via low profile catheters improved electrocardiographic and angiographic markers of myocardial perfusion in several clinical studies 8,9 and reduced adverse events in a single-center trial. 10,11 However, subsequent trials of manual aspiration thrombectomy have not demonstrated a clinical benefit. 1,2,4,12,13 Similarly, results from a pooled

analysis showed that mechanical thrombectomy during STEMI was not superior to conventional PCI alone.

Recommendation-Specific Supportive Text

1. Results from several RCTs have shown that routine manual aspiration thrombectomy prior to PCI does not reduce MI size or improve clinical outcomes as compared with PCI alone. 1,2,4,12,13 In a patient-level, pooled analysis comprising 3 RCTs, aspiration thrombectomy did not reduce the primary endpoint of cardiovascular death at 30 days among patients with STEMI undergoing PPCI (n=18306). 3 Similarly, aspiration thrombectomy did not lower risks for recurrent MI, target vessel revasculariza tion, stent thrombosis, or HF at 30 days or 1 year. With respect to safety, the incidence of stroke or transient ischemic attack at 30 days and 1 year was numerically higher, albeit not statistically sig nificant, among patients who underwent aspiration thrombectomy. Reductions in cardiovascular death were lower while risks for stroke or transient isch emic attack were higher among those with a large thrombus burden treated with aspiration thrombec tomy. Dedicated studies are warranted to evaluate the role of selective aspiration thrombectomy in those high-risk patients most likely to benefit from thrombus removal prior to PCI. Manual aspiration thrombectomy may be performed as a bailout pro cedure to remove thrombus that persists after bal loon angioplasty or stent deployment, particularly with concomitant no-reflow. Estimates from RCT cohorts indicate that $4\%$ to $7\%$ of patients with STEMI undergoing PPCI will require bailout aspira tion thrombectomy. 1,2,10

7.3. Use of Intracoronary Imaging

| Recommendation for Use of Intracoronary Imaging Referenced studies that support recommendation are summarized in ||| |---|---|---| |COR|LOE|Recommendation| |||1. In patients with ACS undergoing coronary stent| |||implantation in left main artery or in complex| |||lesions, intracoronary imaging with intravascular| |||ultrasound (IvUS) or optical coherence tomogra-| |||phy (OCT) is recommended for procedural| ||| guidance to reduce ischemic events.*1-11|

\*Adapted from the “2021 ACC/AHA/SCAI Guideline for Coronary Artery Re vascularization.” 12

Synopsis

Intracoronary imaging serves as a valuable tool for guid ing the placement of coronary stents, particularly in cases involving the left main artery or complex lesions, resulting in greater stent expansion, less stent malapposition, and fewer coronary dissections. 1,2,4,13 IVUS provides a com

prehensive view of the vessel wall, allowing for the evalu ation of plaque burden, calcification extent, lesion length, and external elastic lamina diameter before stent place ment. It also facilitates the assessment of minimum stent area, malapposition, underexpansion, tissue protrusion, edge disease, and edge dissection after stent deploy ment. 14 OCT utilizes infrared light to produce high-res olution images of the vessel wall, offering specific ad vantages in assessing calcium thickness, lipid presence, thrombus formation, fibroatheroma, and plaque rupture, which is particularly helpful in patients with ACS. It is also useful for examining stent strut neointimal thickness, ap position, and edge dissections. However, it has limita tions regarding imaging depth and requires the injection of contrast to clear blood, limiting its utility in cases of os tial left main disease. Both IVUS and OCT play essential roles in evaluating the necessity for lesion preparation, choosing the appropriate stent size, reducing the likeli hood of geographical errors, confirming proper stent ex pansion, identifying complications, and determining the underlying reasons for stent failure. 14,15

Recommendation-Specific Supportive Text

1. Randomized trials including patients with ACS have shown that intracoronary imaging guidance is associated with lower risk of target vessel failure (cardiac death, target vessel MI, or ischemia-driven target vessel revascularization) in patients undergo ing PCI. 1–4 The advantages of intracoronary imag ing are sustained over time and can be extended to less complex lesions. 5 Renovate-Complex PCI (Randomized Controlled Trial of Intravascular Imaging Guidance versus Angiography-Guidance on Clinical Outcomes after Complex Percutaneous Coronary Intervention) demonstrated a significant reduction in target vessel failure with intracoro nary guidance (IVUS or OCT) versus angiographic guidance after a median follow-up of 2.1 years. 1 The OCTOBER (Optical Coherence Tomography Optimized Bifurcation Event Reduction) trial showed a significant reduction in target vessel failure at 2 years with OCT versus angiographic guidance in bifurcation lesions, including left main bifurcations. 4 Randomized trials directly comparing OCT versus IVUS have demonstrated that OCT is noninferior to IVUS for PCI-guidance. 6–8,10 However, the ILUMIEN IV: Optimal PCI (OCT Guided Coronary Stent Implantation Compared with Angiography) trial, the largest trial testing the strategy of imaging guidance with OCT, did not reveal a difference in target vessel failure with OCT in high-risk patients or patients with high-risk lesions; however, the coprimary endpoint of minimal stent area was significantly larger with OCT guidance compared with angiography guidance. 2 The rates of definite or probable stent thrombosis

were also significantly lower with OCT-guided PCI compared with angiography-guided PCI. A minimum stent area of ${<\!4.5}$ to $5.0\;\mathsf{m m}^{2}$ by OCT is considered to be an independent predictor of MACE. 16,17 Two large network meta-analyses showed that, in aggre gate, intracoronary imaging guidance (with either IVUS or OCT) for PCI decreases cardiac death, tar get vessel MI, target lesion revascularization, and stent thrombosis. 11,18

7.4. Management of Multivessel CAD in ACS

7.4.1. Management of Multivessel CAD in STEMI

||| Recommendations for Management of Multivessel CAD in STEMI Referenced studies that support recommendations are summarized in || |---|---|---|---| |the Evidence Table.|the Evidence Table.||| |COR|LOE||| ||||| ||| Recommendations 1. In selected, hemodynamically stable patients with STEMI and multivessel disease (MVD),after successful PCl of the infarct-related artery, PCl of significantly stenosed* noninfarct-related arteries is recommended to reduce the risk of death or Ml and improve angina-related quality of life (QOL).+1-9 2. In appropriate patients with STEMl and complex MVD, after successful PCl of the infarct-related artery, elective CABG surgery for significantly || ||||| |2a||C-EO| 2. In appropriate patients with STEMl and complex MVD, after successful PCl of the infarct-related artery, elective CABG surgery for significantly stenosed noninfarct-related arteries involving the left anterior descendingartery or left main disease is reasonabletoreduice the risk of | |2a| left anterior descendingartery or left main disease is reasonabletoreduice the risk of cardiovascular events.t |C-EO|| |2a|||| |2b|B-R| with STEMI and low-complexity MVD (those not intended for CABG surgery), multivessel PCI of significantly stenosed noninfarct-related arteries at the time of PPCl may be preferred over a staged approach to reduce the risk of || |2b|B-R||| |2b|B-R|B-R| 4. In patients with STEMI complicated by cardiogenic shock, routine PCl of a noninfarct-related arteryshock, routine PCl of a noninfarct-related artery at the time of PPCl should not be performedat the time of PPCl should not be performed because of the higher risk of death or renalbecause of the higher risk of death or renal failure.*13-15 | ||B-R|||

\*Significantly stenosed refers to lesions that are severely diseased as defined by the “2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization” as a visually estimated diameter stenosis severity of ${\geq}70\%$ for non–left main disease and ${\geq}50\%$ for left main disease. 16

†Modified from the “2021 ACC/AHA/SCAI Guideline for Coronary Artery Re vascularization.” 16

Synopsis

Several randomized trials of hemodynamically stable pa tients with STEMI have demonstrated that a strategy of multivessel PCI of significantly stenosed nonculprit ves sels is safe and reduces risk of MACE when compared with PCI of the infarct-related artery alone. 1–8 These trials enrolled a select group of patients with anatomy suitable for PCI and without clinical factors precluding further in vasive therapies. Recent studies suggest a lower risk of MACE (predominantly driven by a lower rate of recur rent ischemia and recurrent MI) when multivessel stent

ing occurs as a single procedure as opposed to when staged. 10–12 The decision to proceed with multivessel stenting and the timing of the procedure should take into account the patient’s clinical and hemodynamic status, the duration and complexity of the infarct-related artery PCI, the complexity of disease in the noninfarct-related artery, the amount of myocardium in jeopardy, and the presence of comorbidities that might favor a conservative approach to care. Few studies of multivessel PCI have directly compared the efficacy of a physiologic-guided PCI versus an angiographic-guided PCI approach. 17,18 A meta-analysis across trials did not suggest any differ ential benefit for complete revascularization based on whether the approach was guided by fractional flow re serve (FFR) or angiography alone. 3

Recommendation-Specific Supportive Text

1. Over the past decade, numerous trials have reported a significant reduction in MACE with complete revas cularization. 1,2,4–8 These studies have demonstrated benefits to complete revascularization either at the time of $\mathsf{P P C}|^{2,5-8}$ or as a staged procedure. 1,2,4,6 The PRAMI (Preventive Angioplasty in Acute Myocardial Infarction) trial, 8 one of the earliest trials of multi vessel PCI, randomized 465 patients with STEMI and MVD to a strategy of complete revasculariza tion versus culprit artery only revascularization. The trial was stopped early due to a significant reduction in the primary composite endpoint (cardiovascular death, nonfatal MI, or refractory angina) with com plete revascularization, with significant reductions in nonfatal MI and refractory angina and a trend in reduction in the rates of cardiovascular death. The COMPLETE (Complete versus Culprit-Only Revascularization Strategies to Treat Multivessel Disease after Early PCI for STEMI) trial 1 randomized 4041 patients with STEMI and significant MVD to a strategy of staged PCI of the non–infarct-related artery (performed up to 45 days post MI) or culprit vessel–only revascularization with PCI reserved for patients with refractory symptoms. At a median follow-up of 3 years, multivessel PCI reduced car diovascular death or MI and cardiovascular death, MI, or ischemia-driven revascularization. This benefit was consistent across all subgroups. Angina-related QOL was also significantly improved with multives sel PCI, with a greater proportion of patients in the complete revascularization arm who were anginafree in long-term follow-up. 9 In a meta-analysis, com plete revascularization reduced cardiovascular death in patients with STEMI. 19 The benefits of complete revascularization with multivessel PCI should not be extrapolated to patients with disease more suited to CABG surgery, because they were excluded from these trials.

2. The trials examining the benefit of multivessel PCI in patients with STEMI and MVD excluded patients intended for CABG surgery. Furthermore, few patients with complex disease, such as chronic total occlusions or involvement of the left main artery, were included in these trials. For this rea son, the benefits of a strategy of multivessel PCI cannot be extrapolated to patients with more com plex noninfarct-related artery disease. In patients with CCD and complex CAD, including complex left main disease, or in patients with diabetes who have MVD involving the left anterior descending artery, CABG surgery is associated with improved event-free survival when compared with PCI. 20–24 As such, a similar benefit of CABG over PCI might be expected for patients with STEMI and complex non–infarct-related artery disease involving the left main or left anterior descending artery or in patients with diabetes and MVD involving the left anterior descending artery, who are stable and remote from their acute infarct, although the optimal timing of CABG is unclear in this setting and needs to take into account increased bleeding risk from DAPT.

3. Performing multivessel PCI at the time of PPCI offers the convenience of a single procedure, allowing for faster recovery, without the risk of repeated arterial access, or the potential for recurrent ischemia before the staged PCI. The BIOVASC (Direct Complete Versus Staged Complete Revascularization in Patients Presenting With Acute Coronary Syndromes and Multivessel Disease) trial 10 randomized 1525 patients with ACS ${\sim}40\%$ with STEMI) and MVD to a strategy of a single setting immediate multivessel PCI or staged multivessel PCI. At 1 year, immediate mul tivessel PCI was noninferior to staged multives sel PCI for the primary endpoint all-cause death, MI, unplanned ischemia-driven revascularization, or cerebrovascular events. When compared with staged PCI, a single procedure multivessel PCI was associated with lower rates of recurrent MI and lower rates of unplanned ischemia-driven revas cularization. The MULTISTARS AMI (Multivessel Immediate Versus Staged Revascularization in Acute Myocardial Infarction) study 11 compared a strategy of a single procedure multivessel PCI with staged multivessel PCI in 840 patients with STEMI and MVD. Immediate multivessel PCI was nonin ferior and superior to staged multivessel PCI for the primary endpoint of death, reinfarction, stroke, unplanned ischemia-driven revascularization, or hospitalization for HF at 1 year. This was largely driven by a lower rate of recurrent ischemia and recurrent infarction in the immediate group. In a network meta-analysis comparing all strategies for managing the non–infarct-related artery, a single

procedure approach for immediate multivessel PCI was preferred followed by staged multivessel PCI. 12 Patients ideally suited for immediate com plete revascularization include those with uncom plicated PCI of the infarct-related artery and low complexity noninfarct-related artery disease with stable hemodynamics, normal LV filling pressures, and normal renal function.

4. In patients with STEMI complicated by cardiogenic shock and MVD, a strategy of multivessel PCI is associated with worse outcomes. 13–15 The CULPRITSHOCK (Culprit Lesion Only PCI versus Multivessel PCI in Cardiogenic Shock) trial 13 randomized 706 patients with AMI, approximately $60\%$ with STEMI, and cardiogenic shock to a strategy of complete multivessel PCI or culprit vessel–only PCI. At 30 days and 1 year, the rates of death or need for renal replacement therapy were significantly higher in the group of patients randomized to multivessel PCI. 13,14 Importantly, the CULPRIT-SHOCK trial only permitted enrollment if there was an identifiable culprit lesion. In situations where an unstable-appearing nonculprit artery lesion was observed, or in those patients with an uncertain culprit lesion, the decision to proceed with multivessel PCI may be more nuanced.

7.4.2. Management of Multivessel CAD in NSTE-ACS

| Referenced studies that support recommendations are summarized in|||| |---|---|---|---| |COR|LOE|Recommendations|Recommendations| ||C-EO||| ||C-EO| In patients with NSTE-ACS with MVD, the mode of revascularization (CABG or multivessel PCI) should be based on the disease complexity and patient's comorbidities. || |Multivessel CAD and Candidates for PCI|||| ||||| ||B-R| 2. In stable patients with NSTE-ACS with MVD but without left mainstenosis who are notintended for CABG surgery and undergoing culprit-lesionfor CABG surgery and undergoing culprit-lesion PCI, PCl of significant nonculprit lesions (at thePCI, PCl of significant nonculprit lesions (at the time of the index procedure or as a stagedtime of the index procedure or as a staged procedure) is recommended to reduce the risk of MACE.1-6 || ||B-R||| |2b|B-R| 3. In patients with NSTE-ACS in whom multivessel PCI is being considered, physiological assessment of a nonculprit stenosis may be || |2b|B-R| PCI is being considered, physiological assessment of a nonculprit stenosis may be considered to guide revascularization decisions.7-9 || ||||| |3: Harm|B-R| 4. In patients with NSTE-ACS complicated by cardiogenic shock, routine PCl of a nonculprit artery at the time of index procedure should not be performed because of the higher risk of death || ||||| |||or kidney failure.*10.11||

\*Modified from the “2021 ACC/AHA/SCAI Guideline for Coronary Artery Re vascularization.” 12

NSTE-ACS. Identification of the culprit artery in these situations might be challenging. 13 Several subsets of pa tients, including those with complex left main disease, complex 3-vessel disease, and diabetes with left an terior descending artery involvement, might be appro priate for CABG surgery. 12 A Heart Team approach is recommended to consider CABG surgery versus mul tivessel PCI based on the complexity of CAD, techni cal feasibility, patient's surgical risk, and the potential for rehabilitation after CABG surgery. Dedicated RCTs comparing multivessel PCI versus culprit-only PCI ex clusively among hemodynamically stable patients with NSTE-ACS are lacking. A large subgroup analysis from an RCT that included both patients with STEMI and NSTE-ACS and several observational studies have sug gested that multivessel PCI among selected patients not intended for CABG reduces risk of MACE. 1–4,6,15 Angio graphic assessment might overestimate the severity of a nonculprit lesion. 16 In one study, routine integration of physiological assessment of a nonculprit artery stenosis in NSTE-ACS led to change in management (ie, from revascularization to medical treatment only) in $38\%$ of the cases. 17

Synopsis

Multivessel coronary disease, defined as angiographi cally significant stenosis $(\geq\!50\%)$ ) in ${\geq}2$ epicardial arter ies, is present in up to $40\%$ to $70\%$ of patients with

Recommendation-Specific Supportive Text

1. Studies evaluating the benefit of multivessel PCI among patients with NSTE-ACS and MVD excluded patients planned for CABG. The poten tial benefit of multivessel PCI cannot be extrap olated to patients with complex CAD. Indeed, certain subsets of patients might derive a survival benefit from CABG, including those with diabetes and disease involving the left anterior descending artery, left main with high complexity, MVD with complex or diffuse CAD, and those with severe LV dysfunction (Table 16). 18–21 Accordingly, a Heart Team approach is recommended to con sider CABG surgery versus multivessel PCI based on the complexity of the CAD, technical

Table 16. Considerations for Choice of Coronary Revascu larization Strategy for Patients With NSTE-ACS and MVD

| In patients with NSTE-ACS and MVD, CABG surgery may be preferred over multivessel PCl in any of the following situations: | |---| |Significant left main coronary stenosis with high-complexity CAD| |Multivessel CADwith complexor diffuse CAD| |Diabetesmellitus andMVDwith the involvement of theLAD| | Multivessel CAD or complex left main CAD with severe left ventricular dysfunction |

Adapted from the “2021 ACC/AHA/SCAI Coronary Revascularization Guide line.” 12

CAD indicates coronary artery disease; CABG, coronary artery bypass graft ing; LAD, left anterior descending artery; MVD, multivessel disease; NSTE-ACS, non–ST-segment elevation acute coronary syndromes; and PCI, percutaneous coronary intervention.

feasibility, patient’s surgical risk, and the poten tial for rehabilitation after CABG surgery in these situations. In patients who are deemed appropri ate for CABG, surgery could be considered prior to hospital discharge. Several observational stud ies have suggested that early CABG (performed within 3 days of presentation) may be associated with similar outcomes compared with delayed CABG. 22–24

2. The FIRE (Functional Assessment in Elderly MI Patients With Multivessel Disease) trial enrolled 1445 elderly patients (median age, 80 years) with multivessel disease (ie, nonculprit artery with minimum vessel diameter ${\tt>}2.5\ \mathsf{m m}$ and angiog raphy estimated stenosis $50\%$ to $99\%$ ) and ACS $\sim\!65\%$ with NSTE-ACS). Multivessel PCI reduced the risk of MACE, as well as reduced all-cause and cardiovascular mortality. The benefit was con sistent between patients with NSTE-ACS versus patients with STEMI. 1 Several observational stud ies and a meta-analysis of observational studies demonstrated that multivessel PCI is associated with a lower incidence of long-term MACE. 2,3,6 Few RCTs have evaluated the optimal timing of a multivessel PCI approach. The SMILE (Single Staged Versus Multistaged PCI in Multivessel NSTEMI Patients) trial enrolled 584 patients and demonstrated that multivessel PCI conducted in a single procedure reduces risk of MACE at 1 year driven by a lower risk of revascularization. 4 The BIOVASC trial randomized 1525 patients with ACS $\langle\sim\!60\%$ with NSTE-ACS) and showed that multivessel PCI in a single procedure was noninferior to staged PCI with respect to MACE at 1 year and without evidence of an interaction between patients with NSTE-ACS versus patients with STEMI. 5,25

3. In a secondary analysis including 328 patients with NSTE-ACS and MVD from the FAME (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation) trial that randomized patients to either angiography-guided PCI (if diameter stenosis ${\ge}50\%$ ) or FFR-guided PCI (if FFR ${\leq}0.80,$ ), FFRguided PCI reduced the number of stents and the incidence of MACE at 2 years. 7 The FRAME-AMI (Fractional Flow Reserve vs. Angiography-Guided Strategy for Management of Non-Infarction Related Artery Stenosis in Patients with Acute Myocardial Infarction) trial enrolled 562 patients with ACS and MVD $(\sim\!53\%$ with NSTE-ACS) and were randomized to FFR-guided PCI (if FFR ${\le}0.80)$ or angiography-guided PCI (diameter ste nosis of ${>}50\%$ ). FFR-guided PCI reduced the number of stents and the risk of MACE at 3.5 years with no evidence of interaction between patients with NSTE-ACS and patients with STEMI.

Of note, the trial was prematurely terminated due to slow recruitment and enrolled ${<}50\%$ of the planned 1292 patients. 9 In the FAMOUS-NSTEMI (Fractional Flow Reserve Versus Angiographically Guided Management to Optimise Outcomes in Unstable Coronary Syndromes) trial, which ran domized 350 patients with NSTE-ACS and MVD to FFR-guided PCI (if FFR ${\leq}0.80,$ ) or angiogra phy-guided PCI (diameter stenosis of ${\tt>}30\%$ ), FFR-guided PCI reduced the number of revascu larization procedures at 1 year. 8

4. In patients with NSTE-ACS complicated by car diogenic shock and MVD, multivessel PCI at the time of the index procedure is associated with worse outcomes. 10,11 The CULPRIT-SHOCK (Culprit Lesion Only PCI versus Multivessel PCI in Cardiogenic Shock) trial randomized 706 patients with AMI and cardiogenic shock (approximately $40\%$ with NSTE-ACS) to multivessel PCI at the time of the index procedure or culprit-only PCI. Multivessel PCI was associated with higher rates of death or need for renal replacement therapy at 30 days and at 1 year. 10,11 Notably, the CULPRIT SHOCK trial enrolled only patients with an iden tifiable culprit lesion. When there is an unstableappearing nonculprit, or uncertain culprit, artery lesion, the decision to proceed with multivessel PCI will be based on the anatomic and clinical circumstances.

8. CARDIOGENIC SHOCK MANAGEMENT

8.1. Revascularization in ACS With Cardiogenic Shock

|||Recommendations for Revascularization in AcS With Cardiogenic|| |---|---|---|---| |Shock|||| ||Referenced studies that support recommendations are summarized in||| |COR|LOE|Recommendations|| ||||| ||B-R||| ||B-R| 1. In patients with ACS and cardiogenic shock or hemodynamic instability, emergency revascularization of the culprit vessel by PCl or with CABG is indicated to improve survival, irrespective of time from symptom onset.1-4 || ||B-R||| ||| 2. In patients with ACS complicated by cardiogenic shock, routine PCl of a noninfarct-related artery || |3:Harm|B-R| shock, routine PCl of a noninfarct-related artery at the time of PPCl should not be performed || |3:Harm|B-R|because of the higher risk of death or renal||

\*Modified from the “2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization.” 8

Synopsis

In patients with STEMI and hemodynamic instability, treatment delays to PPCI are associated with worse survival. 1 In patients with cardiogenic shock, PCI of

the culprit vessel only is recommended. 5,6 Emergency CABG is recommended in those patients in whom PCI is not feasible. 2,9 Immediate revascularization with PCI or CABG is also recommended in high-risk patients with NSTEMI who are in cardiogenic shock. 2–5 The use of MCS devices in patients with cardiogenic shock is covered in Section 8.2, “MCS in Patients With ACS and cardiogenic shock.”

Recommendation-Specific Supportive Text

1. In the SHOCK (Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock) trial, 2 reported in 1999, patients with AMI and cardiogenic shock were randomized to medical therapy or emergency revascularization. Among the patients randomized to revascularization, $64\%$ of patients were referred for PCI and $36\%$ for CABG. The median time from randomization to revascularization was 0.9 hours for PCI and 2.7 hours for CABG. Despite lack of a significant difference in the primary endpoint of mortality at 30 days, emergency revascularization with either PCI or CABG reduced the mortality rate at 6 months, 2 and the mortality benefit was maintained through 1 and 6 years. 10,11 In an obser vational analysis from the FITT-STEMI (Feedback Intervention and Treatment Times in ST-Elevation Myocardial Infarction) trial, for every 10-minute delay in PPCI after 60 minutes from FMC, there were an additional 3 to 4 deaths per 100 with a ${\mathrm{>}80\%}$ mortality rate beyond 6 hours of delay from FMC. 1 Therefore, it is recommended that PPCI should be performed in patients with STEMI and cardiogenic shock as soon as possible, ideally within 90 minutes, to reduce the mortality rate. 1,2 Observational studies suggest that emergency CABG remains a treatment option in patients with cardiogenic shock who are not amenable to primary reperfusion with $\mathsf{P C}|^{3,4}$ or when PCI is unsuccessful. 4,12

2. In patients with STEMI complicated by cardio genic shock and MVD, a strategy of multivessel PCI is associated with worse outcomes. 5–7 The CULPRIT-SHOCK trial 5 randomized 706 patients with AMI (approximately $60\%$ with STEMI) and cardiogenic shock to a strategy of complete multivessel PCI or culprit-only PCI. At 30 days and 1 year, the rates of death or need for renal replacement therapy were significantly higher in the group of patients randomized to multivessel PCI. 5,6 Importantly, the CULPRIT SHOCK trial permitted enrollment only if there was an iden tifiable culprit lesion. In situations where there is an unstable appearing nonculprit artery lesion, or in those patients with an uncertain culprit, the

decision to proceed with multivessel PCI may be more nuanced.

8.2. MCS in Patients With ACS and Cardiogenic Shock

||| Recommendations for McS in Patients With ACS and Cardiogenic Shock Referenced studies that support recommendations are summarized in the Evidence Table. || |---|---|---|---| ||| Recommendations for McS in Patients With ACS and Cardiogenic Shock Referenced studies that support recommendations are summarized in the Evidence Table. || ||||| |COR|LOE|Recommendations|| |2a|B-R| 1. In selected* patients with STEMl and severe or refractory cardiogenic shock, insertion of a microaxial intravascular flow pump is reasonable to reduce death.1 || |2a|B-R| 2.1 In patients with mechanical complication of ACS, short-term MCS devices are reasonable for || | short-term MCS devices are reasonable for hemodynamic stabilization as a bridge to |||| ||surgery.2-4||| |||3. In patients with AMI and cardiogenic shock, the|| | 3:NO benefit |B-R| routine use of intra-aortic balloon pump (IABP) or venoarterial extracorporeal membrane || | 3:NO benefit |B-R||| | 3:NO benefit |B-R|oxygenation (VA-ECMO) is not recommended||

\*See supportive text.

Synopsis

Cardiogenic shock is estimated to occur in approximately $10\%$ of patients with STEMI and is associated with an early mortality rate of $40\%$ to $50\%$ . 10,11 Several types of devices for temporary MCS are available and have been studied in patients with cardiogenic shock with variable efficacy and increased risk of vascular complications. IABP counterpulsation improves coronary perfusion and reduces cardiac afterload. It is relatively easy to use and has a smaller insertion profile, which is associated with lower rates of vascular access site complications when compared with other MCS devices. 12,13 Percutaneous mi croaxial flow pumps unload the LV by draining blood from the LV and pumping it to the ascending aorta. They are dependent on adequate right ventricular function to fill the LV and require adequate oxygenation of blood. VA-ECMO provides both blood flow and oxygenation but increases afterload. Randomized trials of MCS devices remain chal lenging to conduct due to relative lack of equipoise on the part of treating physicians, leading to selective patient enrollment and limiting the generalizability of study results. Although small studies of microaxial flow pumps did not demonstrate clinical benefit for patients with AMI and cardiogenic shock, 14–16 a randomized trial at specialized centers in Europe demonstrated a mortality benefit with use of the microaxial flow pump in selected patients, albeit with increased risk of complications, including limb isch emia and renal replacement therapy. 1 Best practices for insertion of all MCS devices, including the multimodality use of fluoroscopy and ultrasound, should be utilized when feasible for obtaining femoral access. 17–19

Recommendation-Specific Supportive Text

1. The DanGer-SHOCK (Danish-German Cardiogenic Shock) trial enrolled patients with STEMI and cardiogenic shock of ${<}24$ hours duration, defined as hypotension (SBP <100 mm Hg or vasopres sor support), end-organ hypoperfusion (arterial lactate ${\ge}2.5$ mmol/L and/or $\mathsf{S v O}_{2}$ <55% with a normal $\mathsf{P a O}_{2},$ ), and LVEF ${<}45\%$ . Patients who were comatose (Glasgow Coma Scale score ${<\!8}$ ) after out-of-hospital cardiac arrest and patients with overt right ventricular failure were excluded. 1 The study enrolled 360 patients at 14 specialized centers in Europe and randomized them to use of a microaxial flow pump or standard of care. Use of a microaxial flow pump significantly reduced the risk of all-cause mortality at 180 days by $26\%$ (HR, 0.74 $[95\%$ CI, 0.55-0.99]; $P{=}0.04$ ; absolute risk reduction, $12.7\%$ ; number needed to treat $\mathord{=}8$ ) compared with standard of care. The absolute risk reduction seen in this trial is similar to the absolute risk reduction in 6-month mortal ity observed with emergency revascularization in patients with AMI and LV failure in the SHOCK (Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock) trial. 1,20 However, given the increased risks of serious complications like bleeding, limb ischemia, and renal replacement therapy with the microaxial flow pump seen in the DanGer Shock trial, the COR is based on the balance between these risks and the reduction in death. Additionally, the timing of microaxial flow pump placement was not dictated by the trial protocol; thus, the pre ferred timing of placement is unclear. Based on these results, use of a microaxial flow pump is reasonable to reduce mortality in patients with STEMI and cardiogenic shock who have clinical features consistent with the inclusion criteria of the DanGer-SHOCK trial. In particular, patients with STEMI who present with SCAI shock stages C, D, or E, who are noncomatose and have ade quate peripheral vasculature to accommodate large-bore access are reasonable candidates for the microaxial flow pump.

2. Although randomized trial data are lacking, MCS devices can be considered as a bridge to surgery for patients with mechanical complications of AMI when adequate clinical stabilization is required and may allow for further tissue stabilization at the injured site. A systemic review of patients treated with MCS as a bridge to surgical treatment of ventricular septal rupture yielded 111 studies $\mathsf{(n{=}2440}$ ) with almost all patients receiving ini tial IABP support (n=2263). 2 Of the 129 patients who underwent additional MCS device placement

$(77.5\%$ of whom were on VA-ECMO), the low est in-hospital mortality was observed in those treated with VA-ECMO $(29.2\%)$ when compared with those treated with an IABP alone $(52.0\%)$ ). However, 2 database analyses that were not included in the systematic review demonstrated higher in-hospital death with use of VA-ECMO in patients with post-AMI mechanical complica tions. 3,4 Evaluation of the ECLS (Extracorporeal Life Support) Organizations Registry yielded 158 patients with post-AMI mechanical complications who underwent VA-ECMO. 3 Survival to hospital discharge here was low at $37.3\%$ , and complica tions related to VA-ECMO use occurred in $75.3\%$ of patients. Evaluation of the National Inpatient Sample yielded 10726 patients with postSTEMI mechanical complications, and the use of VA-ECMO was associated with increased inhospital mortality (OR, 2.80 $[95\%$ CI, 1.92-4.04]), while the use of an IABP was not associated with lower mortality. 4 Both data sources included use of VA-ECMO at any time during the hospitalization for post-AMI mechanical complications, including use of VA-ECMO postsurgery, a cohort at highest risk of in-hospital mortality.

3. The IABP-SHOCK II (Intraaortic Balloon Pump in Cardiogenic Shock II) trial randomized patients with AMI and severe or refractory cardiogenic shock in whom early revascularization was planned to IABP or no IABP. 5 At 30 days and long-term follow-up, no differences were observed in the pri mary outcome of all-cause death or the secondary biomarker or measures of disease severity end points. 6,7 VA-ECMO has not been shown to reduce death compared with medical therapy alone in patients with cardiogenic shock in the setting of MI but increases major bleeding and vascular complications. 21 The ECMO-CS (Extracorporeal Membrane Oxygenation in the Therapy of Cardiogenic Shock) trial randomized patients with rapidly deteriorating or severe cardiogenic shock to immediate or no immediate VA-ECMO. 8 At 30 days, no differences were observed in the primary composite endpoint of all-cause death, resuscitated cardiac arrest, and implementation of another MCS device with results consistent in the 74 patients with cardiogenic shock related to MI and in the as-treated analysis. The ECLS-SHOCK (Extracorporeal Life Support in Infarct-Related Cardiogenic Shock) trial randomized patients with AMI and severe or refractory cardiogenic shock in whom early revascularization was planned to early ECLS or no ECLS. 9 No differences were observed in the primary outcome of the 30-day mortality rate or secondary outcomes. Moderate or severe bleeding and peripheral vascular complications

requiring intervention were higher in the ECLS versus no ECLS group. Overall, these studies do not support routine use of IABP and VA-ECMO in patients with AMI and cardiogenic shock.

9. ACS COMPLICATIONS

9.1. Mechanical Complications

| Referenced studies that support recommendations are summarized in|||| |---|---|---|---| |COR|LOE|Recommendations|| ||C-EO| 1. Patients with a mechanical complication of ACS should be managed in a facility with || |2@|B-NR| In patients with a mechanical complication of ACS, short-term MCS devices are reasonable for hemodynamic stabilization as a bridge to surgery.1-3 ||

Synopsis

Timely reperfusion therapy has reduced the incidence of mechanical complications (ventricular septal rup ture, mitral valve insufficiency due to papillary muscle infarction or rupture, or free wall rupture) after AMI (Figure 9). 3,5 Although occasionally found incidentally, mechanical complications commonly present with re current or refractory chest pain or a new murmur ac companied by disproportionate HF, cardiogenic shock, or sudden cardiac death on clinical presentation with in the first week after an AMI. Medical therapy alone is associated with high risk of early death 6,7 ; defini tive surgical correction is frequently the treatment of choice. 8,9 Mortality rates with surgery are highest in subjects with cardiogenic shock and in those requir ing early emergency/urgent intervention after AMI. 10,11 Observed mortality rates following delayed surgery (>7 days) are lower but patient selection and survivor bias contribute to this observation. 12,13 The availabil ity of temporary MCS devices has led to increasing trends for delayed surgery due to concerns for the ini tial degree of extensive tissue destruction. 14,15 Delayed surgical intervention may enable hemodynamic stabi lization, lead to recovery of end-organ injury, and pro mote infarct tissue healing and maturation that could facilitate definitive repair. Percutaneous approaches toward repair have been used in patients with prohibi tive surgical risk or contraindications to surgery as a primary or temporizing option in the setting of acute mitral regurgitation and ventricular septal rupture and remain an evolving area of investigation. 16,17 Select pa tients with mechanical complications of ACS may be considered for cardiac transplantation or durable left

ventricular assist device as a primary or bailout treat ment strategy to improve survival. 18

Recommendation-Specific Supportive Text

1. No RCTs evaluate the role of transfer of patients with mechanical complications after MI to dedi cated centers with cardiac surgical expertise. Although overall surgical mortality is approxi mately $40\%$ , it remains the treatment strategy of choice. Hemodynamic deterioration is unpredict able and can be precipitous in previously stable subjects. Consequently, transfer to a Level 1 cardiac intensive care unit (CICU) 19 with access to various temporary MCS devices and multidis ciplinary experienced teams of surgical, inter ventional, HF, and palliative care specialists is recommended. Emerging data following the cre ation of shock teams supports the transfer of hemodynamically unstable patients from com munity hospitals to centers with multidisciplinary expertise. 20,21 Although the exact timing remains uncertain, early corrective surgery is the treat ment of choice for mechanical complications of MI. 8,9,13 The risk of surgical correction is highest when performed in the setting of cardiogenic shock 10,22,23 and appears lower when surgery is delayed. The early hazard with surgery is attrib uted to patient acuity, end-organ injury, and lack of tissue integrity to promote definitive and last ing repair. Selected subjects may be candidates for either definitive or temporizing percutaneous structural intervention as a bridge to definitive surgical intervention. 16,17,24 Given the complexity of decision making, a Heart Team approach to guide feasibility, timing, and nature of corrective intervention as well as the need and selection of MCS support is recommended as soon as a mechanical complication is diagnosed.

2. No RCTs have evaluated the role of MCS in improv ing clinical outcomes in the setting of mechanical complications. The choice of specific MCS should be individualized and guided by patient characteris tics, nature of the mechanical complication, and the hemodynamic profile. In patients with ventricular septal rupture, the use of an IABP has been shown to reduce left-to-right shunting and improve hemo dynamics in patients with and without shock. 25 Favorable hemodynamic effects with IABP are also noted with acute ischemic mitral regurgitation. Various devices have been utilized when IABP fails or if hemodynamic instability remains profound. 1 The use of MCS devices has enhanced hemody namic stabilization to allow the opportunity for con sideration of delayed corrective strategy. 14,15

 Figure 9. Clinical Characteristics of Mechanical Complications of Acute Myocardial Infarction. Contained rupture is the preferred term for an entity sometimes referred to as pseudoaneurysm. HF indicates heart failure; LA, left atrium; LV, left ventricle; and MR, mitral regurgitation. Modified with permission from Damluji et al. 26 Copyright 2025 Devon Medical Art.

9.2. Electrical Complications and Prevention of Sudden Cardiac Death After ACS

| Recommendations for Electrical Complications and Prevention of Sudden Cardiac Death After ACS Referenced studies that support recommendations are summarized in the Evidence Table. ||| |---|---|---| |COR|LOE|Recommendations| |Ventricular Arrhythmias||| ||| 1. In patients post Ml, implantable cardioverter- defibrillator (ICD) implantation is recommended in selected patients with an LVEF |

\*Adapted from the “2017 AHA/ACC/HRS Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death.”

†Adapted from the “2018 ACC/AHA/HRS Guideline on the Evaluation and Management of Patients With Bradycardia and Cardiac Conduction Delay.”

Synopsis

Electrical complications in patients with ACS may cre ate challenges in clinical management due to consider ation for the need of anticoagulant therapy in patients who develop atrial fibrillation (AF) or flutter and possible need for antiarrhythmic therapy and electrophysiologic interventions. Many of these considerations have been addressed in depth in separate guideline documents. 10 Generally, arrhythmic complications increase both mor bidity and mortality rates in patients after ACS. Patients who present with AMI with reduced LVEF $(\leq\!40\%)$ have increased risk of new-onset AF, bradyarrhythmias, and ventricular arrhythmias. 11,12 This risk appears to be in creased in those patients who are not revascularized or receive fibrinolytic therapy compared with those who un dergo PCI. 11

Recommendation-Specific Supportive Text

1. Ventricular arrhythmias are common after ACS and more common in patients with reduced LVEF. MADIT II (Multicenter Automatic Defibrillator Implantation Trial) demonstrated a $31\%$ reduction in all-cause mortality (HR, 0.69 $[95\%$ CI, 0.51- 0.93]) for prophylactic implantation of a cardiac defibrillator in patients with an LVEF ${\leq}30\%$ who were at least 30 days after MI or 3 months after revascularization for MI and had an anticipated life expectancy longer than 1 year. 2 A mortality benefit

Table 17. LVEF and Patient Characteristics Defining an Indication for Prophylactic ICD Implantation for Primary Prevention in Ischemic Heart Disease

|LVEF| Patient Category: All Patients Should Have Expected Survival of ≥1 y | |---|---| |≤300%|NYHA class I,II, or Ill2| |31%-35%|NYHA class Il or 1. 3| |≤400%o|Inducible VT1,4,13|

ICD indicates implantable cardioverter-defibrillator; LVEF, left ventricular ejection fraction; NYHA, New York Heart Association; and VT, ventricular tachycardia.

for prophylactic ICD implantation has also been shown in patients with an LVEF ${\leq}35\%$ and New York Heart Association class II or III HF symp toms, 1,3 as well as in patients with inducible ven tricular tachycardia or ventricular fibrillation and an LVEF ${\leq}40\%^{1,4,13}$ (Table 17).

2. The risk of ventricular arrythmias and sudden car diac death is highest early after MI, although the routine implantation of a defibrillator (for primary prevention) in patients with LV dysfunction early after MI or CABG has not been associated with improved survival. 14–16 In DINAMIT (Defibrillator in Acute Myocardial Infarction Trial), ICD implanta tion led to a $58\%$ reduction in arrhythmic deaths within 6 to 40 days post MI with ejection fraction ${\leq}35\%$ ; however, this was offset by an increase in nonarrhythmic deaths. 16 Sustained episodes of ventricular tachycardia or ventricular fibrillation occurring ${>}48$ hours after reperfusion are asso ciated with an increased risk of death, 12,17 and the risk of sudden cardiac death is highest in the first month. 5 Patients with ventricular arrhythmias should first be managed with beta blockers and/or antiarrhythmic therapy. The benefit of ICD implan tation in patients with persistent or sustained ven tricular arrhythmias and who are ${<\!40}$ days post MI remains unclear. 15,16,18 A single-center observa tional study enrolled patients post STEMI (median, 9 days) and referred those with an LVEF ${\leq}40\%$ for electrophysiologic testing and implanted an ICD only in those with inducible ventricular tachy cardia. Although a randomized comparator arm was unavailable, $22\%$ of those who underwent ICD implantation had ventricular tachycardia termi nated by the device during the first 12 months. 6 The effects of ICD implantation on mortality can not be definitely ascertained, and more research is required. Radiofrequency catheter ablation should be considered in patients with recurrent ventricu lar tachycardia or ventricular fibrillation followed by ICD implantation. 19 Earlier ICD implantation can be considered in patients who have an indication for a permanent pacemaker prior to hospital discharge and in whom LVEF is not expected to recover, but

no evidence was observed to definitively demon strate the safety of this approach. 10,20

3. In the VEST (Vest Prevention of Early Sudden Death) trial, the routine use of a temporary wear able cardioverter-defibrillator did not significantly reduce the primary endpoint (composite of sudden death or death from ventricular tachyarrhythmias at 90 days) in patients with AMI and LVEF ${\leq}35\%$ (relative risk, 0.67 $[95\%$ CI, 0.37-1.21]). 7,21 The secondary endpoint of death from any cause was lower in the wearable vest group compared with the no-device group (relative risk, 0.64 $[95\%$ CI, 0.43-0.98]); only 12 of 48 patients were wearing the device at the time of death. 7 Greater benefit was demonstrated in those who were compliant with the device. 21 As such, use of a wearable car dioverter-defibrillator could be considered in highrisk patients with reduced LVEF as a bridge to consideration for the need for an ICD.

4. Patients with STEMI with second- or third-degree atrioventricular block have higher in-hospital mor tality than those without high-degree atrioventricu lar block. 22,23 Patients who present with ACS with complete heart block have a higher incidence of cardiogenic shock, ventricular arrhythmia, and death. 24,25 In a contemporary cohort of patients with AMI, the incidence of high-degree atrioventricular block has decreased from $4.2\%$ to $2.1\%$ ; however, increased morbidity and mortality remain despite reperfusion therapy in those with high-degree atrio ventricular block. 26,27 A pooled analysis of 30000 patients found that high-degree atrioventricular block, asystole, and electromechanical dissocia tion are infrequent complications of NSTEMI but are associated with increased short-term mortality. High-degree atrioventricular block is not consid ered to be responsible for the increased mortality but is a surrogate marker of larger infarct size. 28 Temporary pacemaker insertion in the setting of ACS in patients with high-degree atrioventricular block and other pacer indications has been found to improve postdischarge survival. 8,9,29 Permanent pacemaker insertion is recommended with unre solved high-degree atrioventricular block that per sists ${>}72$ hours. 20

9.3. Pericarditis Management After MI Synopsis

The diagnostic criteria for post-MI pericarditis are dis played in Table 18. Pericarditis that occurs early after MI typically arises 1 to 3 days after a transmural event and is presumed to be inflammatory in nature due to adjacent myocardial necrosis. These cases of early pericarditis are typically transient, lasting several days, and will resolve

Table 18. Clinical Criteria for Diagnosis of Pericarditis

| Diagnosis Is Made With Presence of Pleuritic Chest Pain and ≥1 of the Following Criteria: | |---| |Friction pericardial rub on auscultation| | Electrocardiographic evidence such as classic PR-segment depression or difusive concave ST-segment elevations, or in the seting of Ml, persistent ST-segment elevations or dynamicT-wave changes | |New or growing pericardial effusion on echocardiography|

MI indicates myocardial infarction.

with conservative therapy. Acetaminophen can be given for symptomatic relief. A second form of pericarditis may occur weeks after MI (Dressler’s syndrome) and is be lieved to be immune-mediated as a response to pericar dial irritation or damage, such as in the setting of any degree of hemopericardium. 1,2 These cases of late peri carditis often require additional therapy (Table 19). Given the rarity of post-MI pericarditis $(0.1\%–0.5\%)$ in the era of early coronary reperfusion therapy, 3 dedicated RCTs of high-dose aspirin are lacking, and data are extrapolat ed from studies of the heterogeneous diagnosis of acute pericarditis. 4 Furthermore, RCTs of colchicine were per formed on a background of high-dose aspirin therapy. 5–7 If symptoms persist despite standard supportive therapy in early pericarditis and in any late pericarditis, high-dose aspirin may be used to reduce symptoms. 4 The use of colchicine should also be considered to reduce symp toms and decrease risk of recurrence 8,9 ; suggested dos ing is summarized in Table 19. The value of a loading dose of colchicine in this setting is unclear. Routine use of high-dose aspirin or colchicine is not indicated for the management of asymptomatic pericardial effusions. 10,11 Glucocorticoids and nonsteroidal anti-inflammatory drugs (other than aspirin) are potentially harmful due to possible increase in risk of recurrent MI or impaired myo cardial healing and risk of rupture. 12,13

9.4. Management of LV Thrombus After MI Synopsis

LV thrombus typically occurs in the setting of large anterior STEMI and can lead to thromboembolic complications, in cluding stroke and systemic embolization. In the era of PCI, the incidence of LV thrombus after ACS has decreased and is estimated to be ${<}5\%$ to $10\%$ in the post-MI popula tion. 1–3 Limited RCT data are available on the contemporary

Table 19. Additional Therapy for Persistent/Late Pericarditis Symptoms

|Medical Therapy|Dosing Schedule| |---|---| |High-dose aspirin|500-1000 mg every 6-8 h until symptoms improve| |Colchicine|0.5-0.6 mg once* or twice daily for 3 mo|

\*Daily dosing should be used in patients who weigh ${<}70~\mathsf{k g}$ and further ad justed in patients with stage 4-5 kidney disease, severe hepatic impairment, or with concomitant P-glycoprotein and/or moderate and severe CYP3A4 inhibitors.

management of LV thrombus, and current management is based mostly on retrospective and observational data and expert consensus. Patients at highest risk for LV throm bus include those with anterior STEMI involving the left anterior descending artery, LVEF ${\tt<}30\%$ (especially in the presence of an LV aneurysm), and longer times to reper fusion. An echocardiogram is the recommended imaging modality for diagnosis, given its wide accessibility and low cost. 4 Cardiac MRI is more sensitive for detection of LV thrombus and may be considered when there is high clini cal suspicion and echocardiogram results are inconclusive. LV thrombus may form later during hospitalization or after discharge; therefore, repeat imaging can sometimes de tect LV thrombus in high-risk patients. 5 Because DAPT is recommended for most patients early after ACS, the ad dition of an anticoagulant for LV thrombus needs to be considered in the context of the patient’s overall bleeding risk versus their risk of an embolic event. Most patients with LV thrombus will warrant anticoagulation for a pe riod of 3 months, at which time the presence of residual thrombus can be assessed by repeat imaging to help de termine whether a more prolonged course is warranted. 1 Although direct oral anticoagulants (DOAC) are routinely used in clinical practice, there are limited data comparing the efficacy of a DOAC versus vitamin K antagonist in the setting of LV thrombus. Observational studies and small RCTs have suggested that DOAC may be noninferior to vitamin K antagonist with respect to mortality, stroke, or LV thrombus resolution, and DOACs may offer an improved bleeding profile. 6 The practical management of LV thrombi is more completely addressed in other documents. 1,6

10. IN-HOSPITAL ISSUES IN THE MANAGEMENT OF ACS

10.1. Cardiac Intensive Care Unit

|Recommendation for CIcU||| |---|---|---| |COR|LOE|Recommendation| ||| Patients with ACS and with ongoing angina, hemo- dynamic instability, uncontrolled arrhythmias, sub- optimal reperfusion, or cardiogenic shock should | ||C-EO|be admitted to a CICU to reduce cardiovascular| ||||

Synopsis

The nurse-to-patient ratio in the CICU should be suf ficient to provide (1) continuous electrocardiographic rhythm monitoring, (2) frequent assessment of vital signs and mental status, and (3) ability to perform rapid car dioversion and defibrillation for arrhythmias. 1,2 Some hos pitals may not have a dedicated CICU but rather care for patients with MI within a general multipurpose ICU; this approach requires trained providers with sufficient expertise in the care of cardiac patients.

Recommendation-Specific Supportive Text

1. Admission to the CICU and optimal length of stay in the CICU after an MI should be based on patients’ risk profile and clinical stability, while considering the patient’s baseline cardiac risk and comorbidities. Patients with ACS with continuing/ ongoing angina, hemodynamic instability, uncon trolled arrhythmias, or a large MI with HF, car diogenic shock, or both, should be admitted to a CICU. 1,2 Patients with ongoing ischemic symptoms should be preferentially triaged for cardiac cath eterization whenever possible. Stable patients with ACS and without recurrent ischemia, significant arrhythmias, pulmonary edema, or hemodynamic instability do not need CICU admission and can be admitted to an intermediate care or telemetry unit. Clinical predictors may be useful for helping identify patients who will require CICU care. For example, the ACTION ICU risk score for CICU admission integrates 9 variables on presentation to the ED including: signs or symptoms of HF, initial heart rate, initial SBP, initial troponin, initial serum creatinine, prior revascularization, chronic lung dis ease, ST-segment depression, and age ${>}70$ years. 3

10.2. Management of Anemia in ACS

|Recommendation for Management of Anemia in Acs||| |---|---|---| |||| |COR|LOE|Recommendation| |2b|B-R| In patients with ACS and acute or chronic anemia, blood transfusion to achieve a hemoglobin level | |2b|B-R|≥10 g/dL may be reasonable to reduce | |||cardiovascularevents.|

Synopsis

Anemia is common in patients with ACS and is asso ciated with worse short- and long-term outcomes. 2–4 Anemia is associated with adverse outcomes irrespec tive of whether the anemia is chronic and due to co morbid conditions, or acute and the result of bleeding related to antithrombotic therapy and/or invasive pro cedures. The adverse effects of anemia may be due to decreased myocardial oxygen delivery, increased myo cardial oxygen demand due to increased cardiac output, or the avoidance of potentially beneficial antithrombotic drugs and/or procedures. In observational studies, blood transfusion has been associated with worse clinical out comes. 5–8 Randomized trials in medically ill patients and those undergoing cardiac surgery have demonstrated similar or better outcomes with a restrictive transfusion strategy (targeting a blood hemoglobin level around 8 g/dL) than with a liberal transfusion strategy (targeting a blood hemoglobin level around 10 g/dL). 9–11

However, randomized trial evidence for populations with ACS suggests possible clinical benefit for a more liberal transfusion strategy targeting a hemoglobin level above 10 g/dL compared with targeting a hemoglobin level above 7 g/dL to 8 g/dL. 1,12,13

Recommendation-Specific Supportive Text

1. The MINT (Myocardial Ischemia and Transfusion) trial randomly assigned 3504 patients with acute STEMI or NSTEMI and anemia with a blood hemo globin level of ${<}10~\mathrm{g/dL}$ ( $13\%$ with recent bleed ing) to a restrictive transfusion strategy (transfusing if the hemoglobin level was ${<}7{\mathrm{-}}8{\mathrm{~}}{\mathsf{g}}/{\mathsf{d}}{\mathsf{L}},$ ) or a liberal transfusion strategy (transfusing if the hemoglobin level was ${<\!10~\mathsf{g}/\mathsf{d L}})$ ). 1 Patients were ineligible for enrollment if they had uncontrolled bleeding, were receiving palliative treatment, or were scheduled to have cardiac surgery. Transfusion could be delayed for patients with volume overload or until day of dialysis in patients with end-stage renal disease. The primary outcome of 30-day death or recurrent MI occurred in $16.9\%$ of patients in the restric tive strategy and $14.5\%$ of patients in the liberal strategy (relative risk, 1.15 $[95\%$ CI, 0.99-1.34]; $P{=}0.07$ ). Death occurred in $9.9\%$ of patients in the restrictive strategy and $\smash{\mathfrak{E}_{\infty}^{\mathrm{e}}\mathfrak{E}_{0}^{\flat}}$ of patients in the liberal strategy (relative risk, 1.19 $[95\%$ CI, 0.94-1.49]), and cardiac death occurred in $5.5\%$ of patients in the restrictive strategy and $3.2\%$ of patients in the liberal strategy (relative risk, 1.74 $[95\%$ CI, $1.26\substack{-2.40]}$ ). Although the MINT trial did not demonstrate a statistically significant reduc tion in its primary endpoint, the results suggest that a liberal blood transfusion strategy targeting a hemoglobin level around 10 g/dL may provide short-term clinical benefit over a restrictive transfu sion strategy targeting a hemoglobin level above 7 g/dL or $8\,\mathrm{g}/\mathrm{d}\mathrm{L}$ in patients with AMI and anemia.

10.3. Telemetry and Length of Stay

||Recommendation for Telemetry and Length of Stay||| |---|---|---|---| |COR|LOE|Recommendation|| ||C-LD| 1. In patients with ACS, telemetry monitoring is recommended to reduce cardiovascular eventsrecommended to reduce cardiovascular events with duration determined by cardiac risk.1.2 || ||C-LD|||

Synopsis

Advances in vascular access methods, coronary revas cularization, and concomitant medical therapies have contributed to shortening length of stay and further facilitated changes in discharge patterns after PCI in the setting of ACS. There remains limited evidence

regarding the optimal length of stay after MI. Patients with STEMI represent a higher risk cohort who may require longer length of stay. Available data suggest that an early discharge strategy of ${\tt<}3$ days from ad mission is not associated with increased mortality for low-risk patients after STEMI who have undergone PCI. 3–8 The Zwolle score has been recommended as a clinical tool to help identify patients after PPCI in STEMI at low risk of death (low-risk patients, score ≤ 3) who can potentially be discharged earlier from the hospital (48 to 72 hours). Predictors of mortality in the Zwolle score include age, Killip class, postprocedural TIMI Flow Grade, 3-vessel disease, anterior infarction, and ischemic time. 3 Optimal length of stay in the set ting of NSTE-ACS has been less rigorously studied. Small retrospective studies have suggested safety of very early or same-day discharge after PCI for patients with ACS, with most $(7\,\uparrow\%)$ of same-day discharge being troponin-negative. 9 Patients being considered for early discharge should be clinically stable without evidence of ongoing ischemia, acute kidney injury, LV dysfunction, HF, and procedural complications and with adequate postdischarge support. 8 Hospitals and care providers should ensure that patients have access to postdischarge prescription medications and adequate follow-up.

Recommendation-Specific Supportive Text

1. The number of studies addressing telemetry dura tion are few and the focus has been on arrhythmia monitoring, not continuous ST-segment moni toring. Continuous ST-segment monitoring can be considered for higher-risk patients, including those with suspected ischemia who are not yet revascularized. 1,10–14 Patients with ACS who are at low risk for cardiac arrhythmias require rhythm monitoring for ${\le}24$ hours or until coronary revas cularization (whichever comes first) in a telemetry unit, while individuals at intermediate to high risk for cardiac arrhythmia may require rhythm moni toring for ${\tt>}24$ hours in a telemetry unit or in an intermediate care unit, depending on the clini cal presentation, degree of revascularization, and early postrevascularization course with input from the treating cardiologist. 10,12–14

10.4. Noninvasive Diagnostic Testing Prior to Hospital Discharge

Recommendation for Noninvasive Diagnostic Testing Prior to Hospital Discharge

|COR|Recommendation|Recommendation| |---|---|---| ||C-LD|1. In patients with ACS, an assessment of LVEF is| ||C-LD|recommended prior to hospital discharge to guide|

Synopsis

In patients with ACS, LV function should be routinely evaluated in patients prior to hospital discharge to help guide therapy and for risk stratification. 1–3 Transthoracic echocardiography is generally the preferred modality be cause it is noninvasive and can provide a comprehensive assessment of ventricular and valvular function, as well as possibly detect LV thrombus or mechanical complications. Transthoracic echocardiography is therefore strongly pre ferred for all patients hospitalized with STEMI because complications may be more likely to be present. In pa tients where transthoracic echocardiography is nondiag nostic, cardiac magnetic resonance imaging is a reason able alternative in clinically stable patients. Alternatively, LV function and some mechanical complications can be assessed invasively with left ventriculography in the car diac catheterization laboratory, but other data regarding valvular function and wall motion are best evaluated with noninvasive methods like transthoracic echocardiography or cardiac magnetic resonance imaging. LV function may also be estimated noninvasively by myocardial perfusion imaging testing, but this will also provide incomplete in formation regarding the presence or absence of other complications of MI. For patients in whom LV function is found to be reduced, a repeat echocardiogram should be performed in 6 to 12 weeks to further guide treatment decisions and for consideration of need for an ICD. 4,5

Recommendation-Specific Supportive Text

1. LV function should be routinely evaluated in patients with ACS prior to hospital discharge because LVEF guides therapeutic interventions and facilitates risk stratification. The diagnosis of LV dysfunction is important because it may trig ger consideration for the initiation or optimization of guideline-directed therapeutic interventions for patients with HF or depressed LV function. It also helps identify patients with reduced LVEF who may require consideration for future primary prevention implantation of an ICD. Besides LVEF, transtho racic echocardiography facilitates the assessment of regional wall motion abnormalities, valvular func tion, mechanical complications, 4 and LV thrombus. 5 In cases in which LV function cannot be adequately assessed despite the use of contrast echocardiog raphy, cardiac magnetic resonance is the preferred imaging modality for clinically stable patients. 6–9

10.5. Discharge Planning

10.5.1. Patient Education

Synopsis

Patient education is universally valued and aims to de liver information from clinicians to patients to improve

health behavior and long-term health-related outcomes. Clinicians are well positioned to engage in meaningful dialogue with patients who have experienced an ACS event about secondary prevention and building self-care skills to manage their condition (Table 20). Recovery represents a teachable moment to provide structured education, including priming the patient to attend car diac rehabilitation (CR). Systematic reviews of educa tional interventions targeting secondary prevention in patients with coronary heart disease, many of whom have ACS, have demonstrated effectiveness in improv ing disease-related knowledge, healthy behaviors (eg, smoking cessation, physical activity, healthy dietary be havior), and medication adherence. 1–3 The magnitude of the effect on each of these outcomes varies by study. Beyond improved knowledge and behavior change, the impact of individualized education for patients with ACS on morbidity and mortality is less clear. A shortcoming of published educational intervention studies to date is that the interventions are markedly heterogeneous but vary in intensity, duration, delivery mode, resources needed, and outcomes measured. Currently, insufficient comparative data are available to guide clinicians about which spe cific educational interventions are best. However, evi dence supports the use of individualized goal setting that demonstrates respect for the patient and their circum stances, structured content that is culturally appropriate, and clearly defined outcomes. 4 Table 20 lists the compo nents that should be discussed with ACS patients at the time of hospital discharge.

10.5.2. Postdischarge Follow-Up and Systems of Care Coordination

Synopsis

Transition from the hospital to home is a critical period for patients with ACS because approximately 1 in 5 patients are readmitted within 30 days of discharge. 1–6 Women, individuals from traditionally underrepresented racial and

Table 20. Essential Components of Patient Education

| Reason for hospitalization (explain reason for admission, diagnostic tests, procedural results) | |---| |Tailored discussion of lifestyle modifications (AHA's Life's Essential 8)5| | Medications (written and verbal instructions including purpose, dose, frequency, potential adverse effects of each medication; refillinstructions; changes to prehospital regimen; importance of adherence) | | Symptom management (what to monitor for and actions to take should symptoms recur, including whom to call) | | Returning to daily routine (when to resume physical activity, sexual activity, work,and travel) | | Psychosocial considerations (open dialogue about symptoms of depression andanxiety) | | Follow-up care (future appointments with cardiology, CR, additional testing postdischarge) |

AHA indicates American Heart Association; and CR, cardiac rehabilitation.

ethnic groups, and patients who require ICU services during their index hospitalization are particularly at risk for readmission. 3 Quality improvement programs such as the Hospital to Home Initiative 7 or the AMI Toolkit 8 pro vide resources to assist clinicians decrease readmission rates and improve medication and CR adherence through increased provider communication and care coordina tion. Transitional care interventions that leverage different types of support (eg, hospital-initiated support, patient and family education delivered before and after discharge, or community-based or chronic disease management mod els of care) are examples of ways to reduce risk of read mission. 9 Hospital-initiated support interventions are asso ciated with reduced mortality rates at 3 months and 1 year as well as a reduction in 30-day readmission rates among patients with AMI. 9,10 Multicomponent integrated care $\mathord{\left<{\vphantom{\left|{\vphantom{\left|{\vphantom{\left|{\vphantom{\left|{\vphantom{\left|{\vphantom{\left|{\vphantom{\left|{\vphantom{\left|{\vphantom{\left|{\vphantom{\left|{\vphantom{\left|{\vphantom{\left|{\vphantom{\left|{\vphantom{\left|{\vphantom{\left|{\vphantom{\left|{\vphantom{\left|{\vphantom{\left|{\vphantom{\left|{\vphantom{\left|{\vphantom{\left|{\vphantom{\left|{\vphantom{\left|{\vphantom{\left|{\vphantom{\left|{\vphantom{\left|{\vphantom{\left|{\vphantom{\left}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}\right|^{2\right|t\right|{\vphantom{\left|{\vphantom{\left|{\vphantom{\left|{\vphantom{\left|{\vphantom{\left|{\vphantom{\left|{\vphantom{\left|{\vphantom{\left|{\vphantom{\left|{\vphantom{\left|{\vphantom{\left|{\vphantom{\left|{\vphantom{\left|{\vphantom{\left|{\vphantom{\left|{\vphantom{\left|{\vphantom{\left|{\vphantom{\left|{\vphantom{\left|{\vphantom{\left|{\vphantom{\left|{\vphantom{\left|{\vphantom{\left}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}\right|^{2\right|\right|\left(\mathrm{d}\right){\mathrm{d}\right){\mathrm{d}}}\right)\right)^{\mathrm{~t~h~e~l~}}\right|^{2}\right|$ quality improvement strategies targeting different do mains of the health care system, health care professionals, or patients) as compared with usual care has been as sociated with reduction of all-cause death, cardiovascular mortality, and all-cause hospitalization. 11 Emerging digital health interventions hold promise to improve the transition from hospital to home. For additional recommendations on nutrition, physical activity, smoking cessation, and alcohol and substance use, refer to the “2023 AHA/ACC/ACCP/ ASPC/NLA/PCNA Guideline for Management of Patients With Chronic Coronary Disease.” 12 Table 21 summarizes the recommended guidance for hospital discharge.

10.5.3. Cardiac Rehabilitation

|Recommendations for CR|||| |---|---|---|---| ||||| |COR|LOE|Recommendations|| ||| 1. Patients with ACS should be referred to an outpatient CR program prior to hospital || |||discharge to reduce death, Ml, hospital readmis-|| |||sions, and improve functional status and QOL1-4|| |2a|B-R| In patients with ACS, a home-based CR program is a reasonable alternative to a center-based CR program to improve functional status and QOL.5-9 || |2a|B-R|||

Synopsis

CR is a multifaceted and comprehensive outpatient inter vention that is considered the standard of care for sec ondary prevention of CVD. The primary goals of CR are modifying CVD risk factors and improving patient func tional capacity and QOL with the goal of reducing subse quent morbidity and mortality. Through a combination of monitored exercise training, health and nutrition education, psychological support, and personalized patient assess ment, including medication optimization (Figure 10), CR has been shown to lower the risk of cardiovascular and all-cause death, reduce hospital readmissions, and to be cost-effective. 10,11 Despite its proven benefits, CR is under utilized and referral rates to CR are low, especially for wom

Table 21. Guidance for ACS Discharge: Best Practices

|Communication|Patient centered, verbally and in writing in patient/caregiver preferred language| |---|---| |Communication|Shared decision-making regarding assessment of goals and preferences should be discussed with patient/caregiver| |Clinical assessment|Address comorbidities and risk factors for recurrent events| |Clinical assessment|Assess for presence of ongoing ischemic symptoms, using standardized instrument ideally embedded into EHR| |Clinical assessment|Assess risk for bleeding related to medications or procedural site| ||| || Assess whether vaccinations are current (eg, influenza) Perform medication reconciliation, including a prescription for sublingual nitroglycerin, unless contraindicated | |Patient/caregiver assessment| Assess capacity for patient/caregiver for self-care (eg, secondary prevention, symptom monitoring, following plan of care, lifestyle changes, contact information for continuing care team) Provideverbal and written educational information related to self-care | ||| ||Use teach-back method for patient/caregiverunderstanding of medication adherence and treatment regimen| |Referrals|Confirm referral to CR| || Provide educational materials related to CR including contact information| |Social determinants of health| Assess and address barriers to obtaining and taking prescribed medications, to include referral to pharmacy assistance programs or social worker as appropriate | ||Assess and address barriers to attending CR, including viability of home-based or hybrid CR|

ACS indicates acute coronary syndromes; CR, cardiac rehabilitation; EHR, electronic health record; and PCI, percutaneous coronary intervention.

en and members of traditionally underrepresented groups. 8 Factors that contribute to this overall low enrollment rate include a poor utilization of a centralized method for referral via the electronic health record, inadequate communication between treatment teams, and perceived inconvenience as well as associated costs for the patient. 8 To increase the utilization of CR, patients should be referred to CR dur ing hospitalization for ACS and prior to discharge. 12 To im prove access for patients who live in rural locations and in areas with no center-based CR, home-based CR options should be considered. These home-based CR programs have similar shorter-term safety and clinical outcomes (eg, improvements in exercise capacity, QOL, blood pressure, cholesterol) as center-based CR. 13–15 More intensive CR programs have been developed with a goal of expanding the benefits of traditional CR programs through addition al exercise and education sessions, as well as placing a greater focus on diet and lifestyle factors. 16–18 Although improved outcomes have been described with an intensive program, 16,19 the studies are observational in nature. Both traditional and intensive CR programs remain underutilized, so the primary emphasis should be on enrollment and ad herence to any CR program. 20

Recommendation-Specific Supportive Text

1. Exercise-based CR programs are associated with improved survival and reduced risk of reinfarction in patients after AMI. 1–4 CR can be enhanced as a com ponent of a multifactorial rehabilitation program with risk factor education and counseling. Patients with ACS who participate in CR have significantly better outcomes compared with those who do not. 1,21,22 In a meta-analysis of 85 RCTs of exercise-based CR in patients with coronary heart disease, the inter vention reduced risk of MI, reduced all-cause hos pitalization, reduced health care costs, and improved

health-related QOL outcomes over 12 months of follow-up. 1 Longer follow-up suggested reductions in cardiovascular mortality. 1,4 CR is particularly beneficial in older patients with CAD, a group that is at a higher risk of losing independence and functioning. 23–26

2. To overcome challenges that have prevented greater patient participation, new strategies and innovative models that utilize digital health tools are emerging to meet the evolving needs of CR patients. CR pro grams have traditionally been delivered via centerbased CR. These programs require patients to be physically present at a facility located in a hospital or outpatient center, which limits access for many patients, especially women and some racial and eth nic groups. 9,27,28 A review of 23 RCTs of home- and center-based CR found that these programs tend to implement the same core components. 13 These include patient assessment of current medical his tory, exercise training, dietary counseling, risk factor management (eg, smoking, lipids, blood pressure, weight, diabetes), and psychological intervention. Comparison of studies in home- and center-based CR indicate a similar improvement in QOL and no sta tistically significant difference in the all-cause mor tality rate up to 12 months after the intervention. 5,6 However, more RCTs are needed with home-based CR in patients with ACS because of an evidence gap (especially in high-risk patients) in assessing the safety of home-based CR in patients at high risk for recurrent ischemic events, as well the impact of a home-based rehabilitation strategy on clinical outcomes such as cardiovascular death, recurrent MI, and rehospitalization. 29 Advances in technology and remote monitoring may help to improve the effi cacy and safety of this approach. Hybrid models that combine elements of both center- and home-based programs may also offer benefits.

 Figure 10. Core Components of Cardiac Rehabilitation. Adapted with permission from Sandesara et al. 30 Copyright 2015 American College of Cardiology Foundation.

11. DISCHARGE: LONG-TERM MANAGEMENT AND SECONDARY PREVENTION

11.1. DAPT Strategies in the First 12 Months Postdischarge

| Recommendations for DAPT Strategies in the First 12 Months Postdischarge Referenced studies that support recommendations are summarized in theEvidenceTable. ||| |---|---|---| |COR|LOE|Recommendations| |DefaultDurationofDAPT||| ||| 1. In patients with ACS who are not at high bleeding risk, DAPT with aspirin and an oral P2Y12 inhibi- tor should be administered for at least 1 year to reduce MACE.1-6 |

||| Recommendations for DAPT Strategies in the First 12 Months Postdischarge (Continued) || |---|---|---|---| |COR|LOE|Recommendations|Recommendations| |Bleeding Reduction Strategies|||| ||| 2. In patients with ACS who have tolerated DAPT with ticagrelor, transition to ticagrelor monotherapy ≥1 || |||month post PCl is useful to reduce bleeding risk7-11|| ||| In patients at high risk of gastrointestinal bleeding, a proton pump inhibitor (PPl) is rec- || |||ommended in combination with DAPT, oral anti-|| |||coagulants or both to reduce risk of bleeding.115|| |2b²|B-R||| |2b²|B-R| 4. In patients with ACS undergoing PCl, de- escalation of DAPT (switching from ticagrelor or prasugrel to clopidogrel) after 1 month may be || ||B-R| prasugrel to clopidogrel) after 1 month may be reasonable to reduce bleeding risk.16-20 || |2b|B-R|5.1|| |2b|B-R| In patients with ACS undergoing PCl who are at high bleeding risk, transition to single antiplatelet therapy (aspirin or P2Y12 inhibitor) after 1 month || ||B-R|may be reasonable to reduce bleeding risk.21||

Synopsis

The addition of an oral P2Y12 inhibitor to aspirin (DAPT) reduces the risk of early and late thrombotic events among patients with ACS regardless of whether they are managed with an invasive strategy. 1–3 Notwithstand ing these salutary benefits, prolonged exposure to DAPT results in excess bleeding that may lead to DAPT inter ruption, 22 which in turn may increase the risk of recur rent ischemic events. 23 Identifying individuals most likely to realize a net clinical benefit or harm from prolonged DAPT has emerged as an important clinical priority. Several tools have been developed that predict the risk of ischemic and/or bleeding events and may be useful when considering how best to personalize care for an individual patient. 24–27 Moreover, alternative antiplatelet strategies have been compared with conventional DAPT with the intent to reduce bleeding while maintaining isch emic efficacy. Growing evidence suggests that a strategy of aspirin discontinuation with ticagrelor monotherapy reduces bleeding. 7–11 Although clopidogrel monotherapy has been studied, 28,29 interpatient variability in pharmaco dynamic response to clopidogrel is substantial 30 and may increase thrombotic risk in certain individuals. To that end, a strategy of clopidogrel monotherapy may increase risk of MACE in patients after ACS when compared with more prolonged DAPT. 29 Additional approaches include aspirin monotherapy 31,32 or a strategy of “de-escalation” (ie, switching from ticagrelor or prasugrel to clopido grel), 16–20 although the safety of these strategies in terms of their effects on risk of MACE is less firmly established. Efficacy and safety of shorter DAPT strategies have not been rigorously studied in patients not undergoing PCI. Figure 11 summarizes the guideline recommendations for DAPT management in patients with ACS during the first 12 months post discharge.

Recommendation-Specific Supportive Text

1. Patients with ACS are characterized by a sus tained prothrombotic state, 33 thus highlighting the need for continued antithrombotic therapy beyond the index presentation. The double-blind placebocontrolled CURE (Clopidogrel in Unstable Angina to Prevent Recurrent Events) trial $\scriptstyle{\mathfrak{n}}=1\,2\,562$ ) demonstrated that DAPT with clopidogrel yields a consistent reduction in both early and late compos ite ischemic events as compared with aspirin alone among patients with NSTE-ACS who were primar ily managed medically. 3,34 The treatment effect was consistent among those treated with or without revascularization. 4 Subsequent studies showed that DAPT with prasugrel or ticagrelor adminis tered for 1 year provides incremental reductions in ischemic events, albeit with excess bleeding, as compared with clopidogrel. 1,2 Although con cordant benefits were also observed among trial

participants requiring surgical revascularization, the safety and efficacy of DAPT should be considered in the context of CABG as a postrandomization event and the high proportion of patients who did not resume study drug after surgery. 4–6 An impor tant consideration in extending the results of clini cal trials that established the benefits of DAPT to contemporary cohorts is that patients at elevated risk for bleeding were typically excluded in early studies. Therefore, the default strategy for a mini mum DAPT duration of 1 year is most applicable to those patients without high bleeding risk present ing with ACS. Moreover, the choice of P2Y12 inhib itor may vary in relation to treatment approach, as described in Section 4.3.2, “Oral P2Y12 Inhibitors During Hospitalization.” In select patients who have tolerated DAPT, it may be reasonable to extend treatment beyond 1 year after considering risks for long-term bleeding and thrombosis. 35–37

2. Results from several randomized trials have con sistently shown that aspirin withdrawal followed by ticagrelor monotherapy after 1 to 3 months of ticagrelor-based DAPT results in less bleed ing without clear excess in MACE, as compared with continued DAPT among patients with ACS undergoing PCI. 7–11 Although studies examining this strategy were characterized by relatively low rates of ischemic events, study-level 38 and individ ual patient data pooled analyses 39–41 have yielded similar results. Although data with clopidogrel have been mixed, concerns have been raised that a strategy of clopidogrel monotherapy started 1 to 2 months after PCI may increase risk of MACE in patients with ACS when compared with longer DAPT. 29 It remains unknown whether this may be explained by excess thrombotic risk in patients displaying inadequate platelet inhibition to clopi dogrel, observed in $30\%$ to $40\%$ of patients after PCI. 30,42 Results from a randomized trial showed that a strategy of P2Y12 inhibitor discontinuation followed by aspirin alone after 6 months of DAPT resulted in excess thrombotic risk among patients with ACS undergoing PCI $\mathsf{\zetan}\mathsf{=}\mathsf{27}\,\mathsf{1}\,\mathsf{2}$ ; $38\%$ STEMI), albeit with less bleeding. 32 Similar findings were observed with earlier P2Y12 inhibitor discontinua tion 3 months after PCI. 31,43 Although the on-treat ment pharmacodynamic effects of ticagrelor and prasugrel are similar, the safety of a strategy of prasugrel monotherapy has not been established in patients $\geq1$ month post ACS; low-dose prasugrel monotherapy (3.75 mg daily) in Japanese patients very early after PCI with ACS or at high bleeding risk may increase 30-day MACE compared with DAPT. 44

3. PPIs reduce the risk of gastrointestinal bleeding among patients receiving aspirin, 14 DAPT, 13 or an

 Figure 11. DAPT Strategies in the First 12 Months Postdischarge. Colors correspond to Class of Recommendation in Table 2. \*High bleeding risk discussed in Section 11.1, “Recommendation-Specific Supportive Text” item 5, and outlined in Table 22. ACS indicates acute coronary syndromes; DAPT, dual antiplatelet therapy; OAC, oral anticoagulant; PCI, percutaneous coronary intervention; and SAPT, single antiplatelet therapy.

oral anticoagulant. 12,15 Because the conversion of clopidogrel to its active metabolite and the metab olism of certain PPIs depend on some common hepatic enzymes (eg, CYP2C19), the potential for a drug-drug interaction exists when both agents are coadministered. The results of several ex vivo studies found that clopidogrel-induced platelet inhibition is attenuated with use of certain PPIs, a pharmacody namic effect that is most pronounced with omepra zole. 45,46 Nonetheless, results from a double-blind, placebo-controlled randomized trial showed no significant differences in ischemic events between omeprazole versus placebo among patients treated with clopidogrel, but PPI use markedly decreased the risk of gastrointestinal bleeding. 13 Moreover, post hoc analyses from several randomized tri als have shown that ischemic risk is not increased when a clinically indicated PPI is used with clopi dogrel. 47,48 Importantly, the antiplatelet effects and clinical efficacy of ticagrelor and prasugrel are not appreciably modified with concomitant PPI use. 48–50 Therefore, it is recommended to administer a PPI in patients with ACS at elevated bleeding risk treated with DAPT or oral anticoagulant.

4. De-escalation implies modulating DAPT intensity by switching from ticagrelor or prasugrel to clopido grel. 51 De-escalation can be guided by the results of platelet function assays that quantify the degree of platelet inhibition among patients treated with clopidogrel. Patients with adequate response may

continue to receive clopidogrel, whereas nonre sponders are switched to a more potent P2Y12 inhibitor. Clopidogrel responsiveness may also be inferred with use of genotyping assays that iden tify polymorphisms in genes involved in clopido grel metabolism. 52 Clinical trials examining guided de-escalation after PCI have either shown a lack of benefit, 16 noninferiority, 20 or reductions in minor bleeding 17 versus conventional DAPT. By con trast, unguided de-escalation is performed without antecedent knowledge of platelet responsiveness. Randomized trials have suggested that unguided de-escalation 1 month after PCI reduces bleeding without incurring ischemic risk as compared with longer term prasugrel- or ticagrelor-based DAPT. 18,19 Pooled analyses have shown that de-escalation (guided or unguided) yields comparable efficacy to DAPT with respect to ischemic events while reducing bleeding. 53,54 However, trials of ticagrelor and prasu grel have suggested that the benefit of more potent P2Y12 inhibitor therapy extends beyond the early phase post ACS, but with increased bleeding. 1,2,55

5. In the MASTER DAPT (Management of High Bleeding Risk Patients Post Bioresorbable Polymer Coated Stent Implantation With an Abbreviated Versus Standard DAPT Regimen) trial, patients at high risk of bleeding who had completed a 4-week course of DAPT after successful PCI with drugeluting stents were randomly allocated to single antiplatelet therapy or more prolonged DAPT $(\geq2$

Table 22. Academic Research Consortium High Bleeding Risk Criteria After PCI

|Major Criteria26|Minor Criteria| |---|---| ||Age≥75y| | Anticipated use of long-term oral anticoagulation (Section 11.1.1, “Antiplatelet Therapy in Patients on Anticoagulation Postdischarge") || | Severe or end-stage CKD (eGFR ||

The presence of at least 1 major or 2 minor criteria helps to identify those at increased risk of bleeding. Modified with permission from Urban et al. 26 Copyright 2019 American Heart Association, Inc. CKD indicates chronic kidney disease; DAPT, dual antiplatelet therapy; eGFR, estimated glomerular filtration rate; NSAID, nonsteroidal anti-inflammatory drugs; ICH, intracranial hemorrhage; and PCI, percutaneous coronary intervention.

additional months). 21 In the absence of oral antico agulant use, the choice of discontinuing aspirin or P2Y12 inhibitor and the choice of P2Y12 inhibitor was at the discretion of the treating physician. An oral anticoagulant was used in $36.4\%$ of patients, and clopidogrel monotherapy was selected in $53.9\%$ of patients randomized to abbreviated DAPT. Compared with standard therapy, an abbre viated antiplatelet strategy demonstrated noninfe riority with respect to composite ischemic events and superiority regarding clinically relevant bleeding over 1 year. Among patients with ACS $\scriptstyle(\mathsf{n}=1780$ ; $30\%$ STEMI) allocated to an abbreviated strategy, clinicians selected a potent P2Y12 inhibitor with ticagrelor use in approximately $25\%$ of patients. 56 Results in the ACS cohort were qualitatively consis tent with the overall trial results with respect to both ischemic and bleeding outcomes. Although the trial demonstrated noninferiority for abbreviated DAPT with respect to MACE in patients at high bleeding risk, it was underpowered to determine the rela tive safety of discontinuing aspirin versus P2Y12 inhibitor. Multiple studies have identified clinical and laboratory predictors of bleeding and/or isch emic risk. 24–27 The Academic Research Consortium determined 20 correlates of bleeding and proposed a consensus-based definition of high bleeding risk as the presence of having at least 1 major or 2 minor criteria at time of PCI (Table 22). 26


11.1.1. Antiplatelet Therapy in Patients on Anticoagulation Postdischarge

Recommendation for Antiplatelet Therapy in Patients on Anticoagulation Postdischarge Referenced studies that support recommendation are summarized in the Evidence Table .

|COR|LOE|Recommendation| |---|---|---| |||1. In patients with ACS who require oral| ||B-R|anticoagulant therapy, aspirin should be| ||B-R|discontinued after 1 to 4 weeks of triple| ||B-R|antithrombotic therapy, with continued use of a| ||B-R| P2Y12 inhibitor (preferably clopidogrel) and an| ||| oral anticoagulant to reduce bleeding risk.*1-5|

\*Modified from the “2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization.” 6

Synopsis

Patients after ACS may frequently have indications for anticoagulant therapy, including AF, venous thrombo embolism, and prosthetic heart valves. Bleeding risks are increased in the setting of triple therapy with the combination of aspirin, P2Y12 inhibitor, and anticoagu lant. Therefore, the benefits of these therapies must be weighed against the risk of bleeding. A growing num ber of studies have demonstrated the overall safety of a strategy of aspirin discontinuation 1 to 4 weeks after ACS or PCI in patients who require anticoagulation after ACS. 1–5 For most patients, a DOAC will be preferred over a vitamin K antagonist due to their favorable efficacy and safety profile. 7 Trials of more potent P2Y12 inhibitors

(ie, prasugrel and ticagrelor) excluded patients requiring long-term anticoagulation; therefore, clopidogrel is gen erally favored as the P2Y12 inhibitor in this setting for most patients. The decision whether to continue antico agulant with or without antiplatelet therapy ${>}12$ months after ACS is addressed in the “2023 AHA/ACC/ACCP/ ASPC/NLA/PCNA Guideline for the Management of Patients with Chronic Coronary Disease.” 8

Recommendation-Specific Supportive Text

1. Several RCTs have demonstrated that the dis continuation of aspirin 1 to 4 weeks after PCI reduces the risk of bleeding in patients with AF with an indication for DAPT and an oral antico agulant. 1–5 Although individual studies were not powered for ischemic endpoints, meta-analyses across randomized trials suggest no difference in mortality, stroke, and overall MACE when aspirin is discontinued for patients on an oral anticoagu lant, albeit with a marginal apparent increase in MI and stent thrombosis. 9–14 An analysis of stent thrombosis rates suggested that $80\%$ of events occurred within 30 days of PCI, with stent throm bosis events numerically less frequent in those receiving aspirin (randomization was approximately 1 week after PCI) compared with placebo in the AUGUSTUS (Antithrombotic Therapy After Acute Coronary Syndrome or PCI in Atrial Fibrillation) trial. 15,16 Therefore, in patients with a high risk of stent thrombosis, aspirin for up to 30 days after PCI could be considered. P2Y12 inhibitor therapy should be continued for at least 12 months after PCI following aspirin discontinuation but could be discontinued earlier in those with multiple risk fac tors for bleeding. 17,18

11.2. Reassessment of Lipid Levels Postdischarge

| Recommendation for Reassessment of Lipid Levels Postdischarge||| |---|---|---| |COR|LOE|Recommendation| ||C-LD| 1. In patients after ACS, a fasting lipid panel is recommended 4 to 8 weeks after initiation or | ||C-LD|dose adjustment of lipid-lowering therapy to| ||C-LD|assess response or adherence to therapy.*12|

\*Modified from the “2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/ AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cho lesterol.” 3

Synopsis

Aggressive LDL-C lowering is an important component of secondary CVD prevention. For every 1.0-mmol/L ( ∼ 39 mg/dL) reduction of LDL-C, an approximate $22\%$ relative reduction in cardiovascular events is observed over a pe riod of 4 to 5 years. 2 Despite the growing number of lipid

lowering therapies currently available, many patients with ACS do not achieve target LDL-C levels. 4,5 The reasons are varied but include underprescribing by providers, cost or insufficient coverage by medical insurance companies, and intolerance to therapies. Many patients are also un willing or unable to readily fill prescriptions at pharma cies or patients self-discontinue therapy early. Providers are not always aware of the barriers that patients may be experiencing; therefore, a conversation between clinician and patient is important to help improve adherence. If ad verse effects are experienced, consideration should be given to subsequent rechallenge at each visit or chang ing to a different type of statin or class of lipid-lowering therapy. Statin intolerance requires exposure to at least 2 different statins with 1 prescribed at the lowest avail able dose. Because risk of MACE is elevated in the early months after ACS, early follow-up visits are important for making appropriate changes to lipid-lowering thera py to help achieve desired LDL-C targets (Section 4.5, “Lipid Management”). Importantly, lipid-lowering therapies should not be downtitrated in response to very low LDL-C concentrations, because current evidence supports that those with very low LDL-C concentrations are at lowest risk of MACE without any clear safety concern. 6–9

Recommendation-Specific Supportive Text

1. Use of high-potency statin therapy has been shown to reduce MACE with the benefit appearing early after ACS and persisting with time. 10 To date, evidence suggests the benefit of lowering LDL-C concentrations may be irrespective of whether it is achieved through high-potency statins or other lipid-lowering therapies; however, the largest body of evidence exists with statin therapies. As such, early intensification of lipid-lowering therapy after ACS is justified. In clinical practice, statin-eligible patients remain undertreated or untreated. 1,11 Early and frequent follow-up, including lipid test ing, is associated with improved adherence to lipid-lowering therapies. 1 In the PALM (Provider Assessment of Lipid Management) registry, less than one-half of adults were on the statin intensity recommended by the guidelines. 12 In a study of US veterans with a history of ACS or coronary revas cularization, less than one-half of patients received intensification of lipid-lowering therapy $(4\,1.9\%$ at 3 months versus $47.3\%$ at 1-year postdischarge). 5 High patient copays and poor coverage of newer lipid-lowering therapies by some prescription plans are factors contributing to suboptimal LDL target attainment. To that end, out-of-pocket costs should be verified and discussed with patients before they fill a prescription for a new lipid-lowering therapy. Education about the importance of lipid-lowering therapies should be discussed with patients at

visits to allow them the opportunity to ask ques tions and review potential barriers. For the man agement of lipid-lowering therapy initiated prior to discharge and continued after hospital discharge, refer to Section 4.5, “Lipid Management.”

11.3. SGLT-2 Inhibitors and GLP-1 Receptor Agonists

Synopsis

The cardiovascular benefits of both sodium glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists are well document ed in stable patients with ASCVD and type 2 diabetes, 1–6 as well as in patients with HF regardless of diabetes sta tus. 7–11 GLP-1 receptor agonists may lead to weight loss in many patients, and semaglutide has been shown to reduce the risk of MACE in overweight or obese patients with stable ASCVD but has not been studied early after ACS. 12 SGLT-2 inhibitors may increase the risk of urinary tract infection, genital mycotic infection, hypovolemia, and acute kidney injury (while offering longer term renal benefit in patients with diabetes). Due to a higher risk of diabetic and euglycemic ketoacidosis in the periopera tive period, canagliflozin, dapagliflozin, and empagliflozin should be stopped ${\geq}3$ days and ertugliflozin ${\ge}4$ days prior to scheduled surgery, including CABG. 13–15

The efficacy and safety of SGLT-2 inhibitors have now been studied in 2 large trials of patients after MI. In patients without diabetes or HF, dapagliflozin was not shown to reduce the risk of cardiovascular death or HF hospitalization in patients with AMI and impaired LV systolic function. 16 Similarly, empagliflozin did not signifi cantly reduce all-cause death or first HF hospitalization in patients without prior HF who were hospitalized with AMI and found to have impaired LV systolic function with or without signs of congestion. However, empagliflozin did reduce HF hospitalizations in this population. 17 No new safety concerns were identified. Therefore, use of an SGLT-2 inhibitor does not need to be deferred in patients with an indication for its use at hospital discharge.

11.4. Use of Chronic Colchicine

| Recommendation for Use of Chronic Colchicine Referenced studies that support recommendation are summarized in the Evidence Table. ||| |---|---|---| |COR|LOE|Recommendation| |2b|B-R| 1. In patients after ACS, low-dose colchicine may be reasonable to reduce risk of MACE.1-5 |

Synopsis

Colchicine is a botanical-derived anti-inflammatory agent that has been used for millennia in the treatment of gout.

Colchicine reduces neutrophil adhesion to endothelial cells and platelets and has been shown to reduce highsensitivity C-reactive protein concentration and low-at tenuation plaque volume in patients already on aspirin and statin therapy. 6–9 Colchicine is associated with a lower risk of MI in patients with gout, as well as in pa tients with CAD, including those with prior MI. 1,4,5,10,11 Al though gastrointestinal events were historically reported at a higher rate in patients on colchicine, this rate does not differ from placebo at the lower once daily dosing. 5 A meta-analysis of the studies examining colchicine in pa tients with CAD reported no difference in all-cause death with colchicine versus placebo, but a nonsignificant trend was observed toward an increased risk of noncardiovas cular death that requires further study. 5 To date, no po tential pathogeneses of the noncardiovascular deaths have been consistently shown to explain the numerical differences in noncardiovascular death. 5

Recommendation-Specific Supportive Text

1. COLCOT (Colchicine Cardiovascular Outcomes Trial) randomized patients ${\le}30$ days (median, 14 days) after MI to low-dose colchicine versus pla cebo. 2 Colchicine reduced the primary outcome of cardiovascular death, resuscitated cardiac arrest, MI, stroke, or urgent coronary revascularization by $32\%$ (median follow-up, 22.6 months). Although directional consistency was seen across individual components, this benefit was driven by a reduction in hospitalizations for angina requiring revascular ization and stroke. The smaller COPS (Colchicine in Patients With ACS) study randomized patients dur ing their index hospitalization of ACS to colchicine versus placebo. 3 The primary endpoint of all-cause death, ACS, unplanned ischemia-driven urgent revascularization, and noncardioembolic ischemic stroke was numerically, but not significantly, lower for patients on colchicine ( $\scriptstyle{P=0.09,}$ ). Although deaths were infrequent, more deaths occurred for patients on colchicine than on placebo (8 versus 1; ${\it P}{=}0.017$ ) due to more noncardiovascular deaths. In a post hoc analysis, the composite outcome of cardiovascular death, ACS, stroke, or urgent revascularization was lower for colchicine than pla cebo. The LoDoCo2 (Low-Dose Colchicine-2) trial enrolled patients with stable ${\left(>6\right)}$ months) coronary disease, demonstrating a reduction in the compos ite of cardiovascular death, MI, ischemic stroke, or ischemia-driven coronary revascularization with colchicine (median follow-up, 28.6 months); find ings were consistent in the $84\%$ of patients with prior ACS. 4,12 Pooled data from these large tri als confirmed a reduction in the incidence of MACE with colchicine versus placebo. 5 Colchicine should not be administered in patients with blood

dyscrasias, renal failure (creatinine clearance <15 mL/min), severe hepatic impairment, or with con comitant P-glycoprotein and/or strong CYP3A4 inhibitors. Although the trials studied a dose of 0.5 mg daily, daily dosing of 0.5 mg or 0.6 mg may be considered. There are ongoing trials studying the efficacy of colchicine in patients after MI.

11.5. Immunization

| RecommendationforImmunization Referenced studies that support recommendation are summarized in the Evidence Table. ||| |---|---|---| |COR|LOE|Recommendation| ||| 1. In patients with ACS without a contraindication, annual influenza vaccination is recommended to reduce the risk of death and MACE.1-4 |

Synopsis

Influenza infection is associated with increased risks of cardiovascular morbidity and mortality. 5 Previous studies have shown that influenza infection may contribute to atherogenesis and plaque destabilization, thereby pre cipitating the occurrence of ACS. 6,7 Influenza vaccine has been shown to reduce the risk of death and MACE in patients after ACS and ASCVD and should therefore be administered in patients without contraindication. 1–3,5,8 Other illnesses such as COVID-19 and pneumococcal pneumonia increase risk of cardiovascular events and death in patients with ASCVD. However, randomized trial data are lacking to support routine administration of other vaccines for patients at time of hospitalization for ACS. As such, regular immunization schedules are sup ported for all patients per the US Centers for Disease Control and Prevention recommendations in the absence of contraindication. 9

Recommendation-Specific Supportive Text

1. In the FLUVACS (Flu Vaccination in Acute Coronary Syndromes and Planned Percutaneous Coronary Interventions) study, cardiovascular death was lower in patients who received influenza vac cination compared with the control group at both 6-month $(2\%$ versus $8\%$ ) and 1-year follow-up $(6\%$ versus $17\%$ ). The triple composite endpoint of cardiovascular death, nonfatal MI, and rehospital ization for severe recurrent ischemia at 1 year was significantly lower in the vaccine group compared with controls. 2,10 Among patients admitted with MI or high-risk coronary heart disease, influenza vac cine administered within 72 hours of an invasive coronary procedure or hospitalization resulted in a lower risk of the composite primary outcome of allcause death, MI, or stent thrombosis and a lower

risk of cardiovascular death compared with pla cebo at 1 year. 1

12. EVIDENCE GAPS AND FUTURE DIRECTIONS

The treatment of ACS has been the subject of thou sands of clinical trials comprising very large numbers of patients. As such, its management is guided by the larg est evidence base in clinical medicine. Despite this, there are numerous unanswered questions, evidence gaps, and areas for further study. Some of these areas have been addressed by observational studies but were not in cluded in this guideline because the LOE was insufficient to guide clinical practice. Other areas were not included because they are less well defined and require more de tailed study. This section summarizes some higher prior ity evidence gaps and areas for future study.

INITIAL EVALUATION AND MANAGEMENT

Although the 2025 ACS guideline recognizes the value of risk scores in estimating the risk of death or recurrent MI, limited prospective randomized data are available as to whether risk scores should be used to determine treat ment strategies. The highest risk patients are those who present after a cardiac arrest. Although the data support an invasive approach in patients who have been resus citated and who have evidence of ST-segment elevation on the postarrest ECG, any potential benefit of coronary angiography may be attenuated in those who are coma tose. Similarly, it is less clear whether reperfusion with either fibrinolysis or primary PCI provides clinical benefit in patients with ST-segment elevation who present late after symptom onset (12 to 48 hours) but who are no longer symptomatic. Further research is needed to define the role of coronary angiography and revascularization in these patient subgroups.

In-Hospital Management of ACS

Patients with ACS are placed on telemetry to monitor for life-threatening arrhythmias or for rhythm disturbanc es that may require further therapy (eg, atrioventricular block, AF). Given the length of stay for most patients with ACS has decreased significantly, the optimal duration of telemetry monitoring with contemporary management is unclear. The increasingly rapid triage and timing of inva sive risk stratification also calls into question the value of “preloading” of oral P2Y12 inhibitors, with preloading de fined as administering the loading dose prior to coronary angiography. As outlined in this document, clinical trials of preloading have not shown a compelling benefit when coronary angiography occurs rapidly after the patient’s clinical presentation. Nonetheless, the pharmacodynamic

effects of clopidogrel are delayed due to its need to be metabolized to its active metabolite, and there are re ports that the antiplatelet effects of all P2Y12 inhibitors may be delayed in patients with STEMI. In this context, parenteral P2Y12 inhibition could be considered but has not yet been compared to a strategy of more potent oral P2Y12 inhibitor administration. Other drug therapies in need of further evaluation in the ACS setting include the utility of sacubitril-valsartan, nonstatin lipid-lowering therapies (including clinical outcome studies for PCSK9 inhibitors early after ACS), and GLP-1 receptor agonists for reducing short- and long-term MACE after ACS. The clinical benefit of beta blockers in the setting of patients with NSTE-ACS requires further study, as well as the op timal duration of their use after ACS.

For patients with MVD found during coronary angiog raphy, there are several remaining gaps in evidence. In patients with NSTEMI, the role of multivessel PCI versus culprit-only PCI needs further supportive data. As a cor ollary, whether multivessel PCI in the ACS setting should be guided by angiography or physiology is still a matter of debate. Finally, as noted in this guideline, the recom mendations for PCI of nonculprit arteries in patients with STEMI are for patients who are not intended for CABG, which is a qualifier based on the inclusion criteria of the randomized trials. The optimal strategy for patients who have more complex anatomy is less clear.

The 2025 ACS guideline includes a new recommen dation regarding the management of cardiogenic shock using the microaxial flow pump MCS device. Because the benefit of this device was offset by an increase in serious complications, more data are needed to guide the selection of patients for MCS, the timing of MCS placement and duration of support, and strategies to reduce the risks of vascular complications, bleeding, and limb ischemia.

DISCHARGE STRATEGIES AND SECONDARY PREVENTION

One of the most important areas needing further clarifi cation is the timeline defining the transition of a patient from ACS to chronic coronary syndrome. The 2025 ACS guideline does not define this largely because no data exist to guide any recommendations. Moreover, it is likely that this transition is highly individualized and accounts for the patient’s risk at initial presentation, the status of resid ual unrevascularized CAD, control of cardiovascular risk factors, and bleeding risk with continued antithrombotic therapy. Once a patient is deemed to have transitioned to having a “chronic coronary syndrome,” the question of how to or whether to de-escalate antiplatelet therapies is unclear. These decisions may also be influenced by complications of ACS requiring additional antithrombotic therapy such as LV thrombus from a large anterior wall

MI. The role of DOACs in this setting appears prudent but is not supported by a robust body of data. Other com plications such as post-MI pericarditis now have several therapeutic options, but no comparative data are available to help determine which approach is optimal.

With respect to long-term secondary prevention, more research is needed to determine whether home-based CR provides the same benefit as facility-based programs and results in higher rates of adherence. Randomized trials of GLP-1 receptor agonists post MI will be impor tant to understand the role of these agents in reducing long-term risk in patients with diabetes or those who are overweight or with obesity. Finally, data are lacking on the use of high-dose aspirin in those with post-MI pericar ditis, and additional data would be useful to confirm the efficacy of colchicine post ACS.

PEER REVIEW COMMITTEE MEMBERS

Hani Jneid, MD, FACC, FAHA, FSCAI, Chair; Craig J. Beavers, PharmD, FACC, FAHA; Theresa Beckie, PhD, RN, FAHA; Jim Blankenship, MD, MACC; Deborah Di ercks, MD, FACC; Bruce Lo, MD\*; Clauden Louis, MD, FACC; Faisal M. Merchant, MD, FACC; Noreen Nazir, MD, FACC; Derek So, MD, MSc, FACC; Matthew Tomey, MD, FACC, FAHA, FSCAI; Frederick Welt, MD, FACC†

Heart Association

ACC/AHA JOINT COMMITTEE ON CLINICAL PRACTICE GUIDELINES MEMBERS

Catherine M. Otto, MD, FACC, FAHA, Chair; Sunil V. Rao, MD, FACC, FSCAI, Chair-Elect; Joshua A. Beckman, MD, MS, FAHA, FACC, Immediate Past Chair‡; Anastasia Armbruster, PharmD, FACC; Vanessa Blumer, MD, FACC; Leslie L. Davis, PhD, RN, ANP-BC, FACC, FAHA; Lisa de las Fuentes, MD, MS, FAHA‡; Anita Deswal, MD, MPH, FACC, FAHA‡; Victor A. Ferrari, MD, FACC; Stephen E. Fremes, MD, FACC; Mario Gaudino, MD, FACC, FAHA; Adrian F. Hernandez, MD, FAHA‡; Hani Jneid, MD, FACC, FAHA; Heather M. Johnson, MD, MS, FACC, FAHA; W. Schuyler Jones, MD, FACC; Sadiya S. Khan, MD, MSc, FACC, FAHA; Prateeti Khazanie, MD, FAHA‡; Michelle M. Kittleson, MD, FACC, FAHA; Venu Menon, MD, FACC, FAHA; Debabrata Mukherjee, MD, MS, FACC, FAHA, MSCAI; Latha Palaniappan, MD, MS, FACC, FAHA‡; Tanveer Rab, MD, FACC, MSCAI‡; Garima Sharma, MBBS, FACC, FAHA; Daichi Shimbo, MD; Jacqueline E. TamisHolland, MD, FACC, FAHA, FSCAI‡; Y. Joseph Woo, MD, FACC, FAHA‡; Boback Ziaeian, MD, PhD, FACC, FAHA

PRESIDENTS AND STAFF

American College of Cardiology

Cathleen Biga, MSN, FACC, President Cathleen C. Gates, Chief Executive Officer Richard J. Kovacs, MD, MACC, Chief Medical Officer Justine Varieur Turco, Divisional Vice President, Scientific Publications and Guidelines Mindy J. Saraco, MHA, Director, Clinical Policy and Guidelines Grace D. Ronan, Senior Production and Operations Man ager, Clinical Policy Publications Leah Patterson, Project Manager, Clinical Content Devel opment

American College of Cardiology/American Heart Association

Thomas S.D. Getchius, National Senior Director, Guide lines Abdul R. Abdullah, MD, Director, Guideline Science and Methodology

American Heart Association

Keith Churchwell, MD, FAHA, President Nancy Brown, Chief Executive Officer Mariell Jessup, MD, FAHA, Chief Science and Medical Officer Nicole Aiello Sapio, EdD, Executive Vice President, Office of Science Strategies and Operations Radhika Rajgopal Singh, PhD, Senior Vice President, Office of Science and Medicine Prashant Nedungadi, BPharm, PhD, National Vice President, Science and Medicine, Clinical Guidelines Paul St. Laurent, DNP, RN, National Vice President, Office of Science and Medicine Jody Hundley, Senior Production and Operations Manager, Scientific Publications, Office of Science Operations

ARTICLE INFORMATION

This document was approved by the American College of Cardiology Clinical Pol icy Approval Committee and the American Heart Association Science Advisory and Coordinating Committee in October 2024, the American College of Cardiol ogy Science and Quality Committee in October 2024, and the American Heart Association Executive Committee in November 2024.

Supplemental materials are available with this article at https://www.ahajour nals.org/doi/suppl/10.1161/CIR.0000000000001309

This article has been copublished in the Journal of the American College of Cardiology .

Copies: This document is available on the websites of the American Heart Association (professional.heart.org) and the American College of Car diology (www.acc.org). A copy of the document is also available at https:// professional.heart.org/statements by selecting the “Guidelines & State ments” button. To purchase additional reprints, call 215-356-2721 or email Meredith.Edelman@wolterskluwer.com.

The expert peer review of AHA-commissioned documents (eg, scientific statements, clinical practice guidelines, systematic reviews) is conducted by the AHA Office of Science Operations. For more on AHA statements and guide lines development, visit https://professional.heart.org/statements. Select the

“Guidelines & Statements” drop-down menu near the top of the webpage, then click “Publication Development.”

Permissions: Multiple copies, modification, alteration, enhancement, and dis tribution of this document are not permitted without the express permission of the American Heart Association. Instructions for obtaining permission are located at https://www.heart.org/permissions. A link to the “Copyright Permissions Request Form” appears in the second paragraph (https://www.heart.org/en/about-us/ statements-and-policies/copyright-request-form).

REFERENCES

PREAMBLE

1. Committee on Standards for Systematic Reviews of Comparitive Effective ness Research, Institute of Medicine (US). Finding what works in healthcare: standards for systematic reviews. National Academies Press ; 2011. 2. Anderson JL, Heidenreich PA, Barnett PG, et al. ACC/AHA statement on cost/value methodology in clinical practice guidelines and performance measures: a report of the American College of Cardiology/American Heart Association Task Force on Performance Measures and Task Force on Prac tice Guidelines. Circulation . 2014;129:2329–2345. 3. ACCF/AHA Task Force on Practice Guidelines. Methodology Manual and Policies From the ACCF/AHA Task Force on Practice Guidelines. American College of Cardiology and American Heart Association. 2010. Accessed June 3, 2024. https://www.acc.org/-/media/Non-Clinical/Files-PDFs-Excel-MS-Word-etc/Guidelines/About-Guidelines-and-Clinical-Documents/ Methodology/2014/Methodology-Practice-Guidelines.pdf?la=en& hash=157B7835091CF7856B26528717BE14B33BE8226F and https:// professional.heart.org/-/media/phd-files/guidelines-and-statements/ methodology_manual_and_policies_ucm_319826.pdf. 4. Halperin JL, Levine GN, Al-Khatib SM, et al. Further evolution of the ACC/ AHA clinical practice guideline recommendation classification system: a re port of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation . 2016;133:1426–1428. 5. Arnett DK, Goodman RA, Halperin JL, et al. AHA/ACC/HHS strategies to enhance application of clinical practice guidelines in patients with cardio vascular disease and comorbid conditions: from the American Heart Asso ciation, American College of Cardiology, and US Department of Health and Human Services. Circulation . 2014;130:1662–1667. 6. Levine GN, O’Gara PT, Beckman JA, et al. Recent innovations, modifications, and evolution of ACC/AHA clinical practice guidelines: an update for our constituencies: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation . 2019;139:e879–e886.

1.4. Scope of the Guideline

1. O’Gara PT, Kushner FG, Ascheim DD, et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation . 2013;127:e362–e425. 2. Amsterdam EA, Wenger NK, Brindis RG, et al. 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation . 2014;130:e344–e426. 3. Levine GN, Bates ER, Blankenship JC, et al. 2015 ACC/AHA/SCAI Fo cused update on primary percutaneous coronary intervention for patients with ST-elevation myocardial infarction: an update of the 2011 ACCF/ AHA/SCAI guideline for percutaneous coronary intervention and the 2013 ACCF/AHA guideline for the management of ST-elevation myocardial in farction. Circulation . 2016;133:1135–1147. 4. Lawton JS, Tamis-Holland JE, Bangalor S, et al. 2021 ACC/AHA/SCAI guideline for coronary artery revascularization: a report of the American Col lege of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation . 2022;145:e18–e114. 5. Levine GN, Bates ER, Bittl JA, et al. 2016 ACC/AHA guideline focused update on duration of dual antiplatelet therapy in patients with coronary artery disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation . 2016;134:e123–e155. 6. Martin SS, Aday AW, Almarzooq ZI, et al. 2024 Heart disease and stroke statistics: a report of US and global data from the American Heart Associa tion. Circulation . 2024;149:e347–e913. 7. Centers for Disease Control and Prevention and National Center for Health Statistics. National Health and Nutrition Examination Survey (NHANES), 2017-2020. Accessed April 16, 2024. https://wwwn.cdc.gov/nchs/ nhanes/continuousnhanes/default.aspx?Cycle=2017-2020. 8. Tsao CW, Aday AW, Almarzooq ZI, et al. Heart disease and stroke statis tics-2023 update: a report from the American Heart Association. Circulation . 2023;147:e93–e621. 9. Roe MT, Messenger JC, Weintraub WS, et al. Treatments, trends, and out comes of acute myocardial infarction and percutaneous coronary interven tion. J Am Coll Cardiol . 2010;56:254–263. 10. Bishu KG, Lekoubou A, Kirkland E, et al. Estimating the economic burden of acute myocardial infarction in the US: 12 year national data. Am J Med Sci . 2020;359:257–265. 11. Cowper PA, Knight JD, Davidson-Ray L, et al. Acute and 1-year hospitaliza tion costs for acute myocardial infarction treated with percutaneous coro nary intervention: results from the TRANSLATE-ACS registry. J Am Heart Assoc . 2019;8:e011322. 12. Chaudhry SI, Khan RF, Chen J, et al. National trends in recurrent AMI hospi talizations 1 year after acute myocardial infarction in Medicare beneficiaries: 1999-2010. J Am Heart Assoc . 2014;3:e001197. 13. Brown TM, Deng L, Becker DJ, et al. Trends in mortality and recurrent coro nary heart disease events after an acute myocardial infarction among Medi care beneficiaries, 2001-2009. Am Heart J . 2015;170:249–255. 14. Graham G. Racial and ethnic differences in acute coronary syndrome and myocardial infarction within the United States: from demographics to out comes. Clin Cardiol . 2016;39:299–306. 15. Nadruz W Jr, Claggett B, Henglin M, et al. Widening racial differences in risks for coronary heart disease. Circulation . 2018;137:1195–1197. 16. Nanna MG, Navar AM, Zakroysky P, et al. Association of patient perceptions of cardiovascular risk and beliefs on statin drugs with racial differences in statin use: insights from the Patient and Provider Assessment of Lipid Management Registry. JAMA Cardiol . 2018;3:739–748. 17. Aggarwal R, Chiu N, Wadhera RK, et al. Racial/ethnic disparities in hyper tension prevalence, awareness, treatment, and control in the United States, 2013 to 2018. Hypertension . 2021;78:1719–1726. 18. Golomb M, Redfors B, Crowley A, et al. Prognostic impact of race in patients undergoing PCI: analysis from 10 randomized coronary stent trials. J Am Coll Cardiol Intv . 2020;13:1586–1595. 19. Lewey J, Choudhry NK. The current state of ethnic and racial disparities in cardiovascular care: lessons from the past and opportunities for the future. Curr Cardiol Rep . 2014;16:530. 20. Khraishah H, Daher R, Garelnabi M, et al. Sex, racial, and ethnic dispari ties in acute coronary syndrome: novel risk factors and recommendations for earlier diagnosis to improve outcomes. Arterioscler Thromb Vasc Biol . 2023;43:1369–1383. 21. Ferry AV, Anand A, Strachan FE, et al. Presenting symptoms in men and women diagnosed with myocardial infarction using sex-specific criteria. J Am Heart Assoc . 2019;8:e012307. 22. Lichtman JH, Leifheit EC, Safdar B, et al. Sex differences in the presenta tion and perception of symptoms among young patients with myocardial infarction: evidence from the VIRGO study (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients). Circulation . 2018;137:781– 790. 23. van Oosterhout REM, de Boer AR, Maas A, et al. Sex differences in symp tom presentation in acute coronary syndromes: a systematic review and meta-analysis. J Am Heart Assoc . 2020;9:e014733. 24. Canto JG, Goldberg RJ, Hand MM, et al. Symptom presentation of women with acute coronary syndromes: myth vs reality. Arch Intern Med . 2007;167:2405–2413. 25. Peters SAE, Colantonio LD, Zhao H, et al. Sex differences in high-intensity statin use following myocardial infarction in the United States. J Am Coll Cardiol . 2018;71:1729–1737. 26. Koopman C, Vaartjes I, Heintjes EM, et al. Persisting gender differences and attenuating age differences in cardiovascular drug use for preven tion and treatment of coronary heart disease, 1998-2010. Eur Heart J . 2013;34:3198–3205. 27. Peters SAE, Muntner P, Woodward M. Sex differences in the prevalence of, and trends in, cardiovascular risk factors, treatment, and control in the United States, 2001 to 2016. Circulation . 2019;139:1025–1035. 28. Sorensen NA, Neumann JT, Ojeda F, et al. Relations of sex to diagnosis and outcomes in acute coronary syndrome. J Am Heart Assoc . 2018;7:e007297. 29. Sarma AA, Braunwald E, Cannon CP, et al. Outcomes of women compared with men after non-ST-segment elevation acute coronary syndromes. J Am Coll Cardiol . 2019;74:3013–3022. 30. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the man agement of blood cholesterol: a report of the American College of Cardiol ogy/American Heart Association Task Force on Clinical Practice Guidelines. Circulation . 2019;139:e1082–e1143. 31. Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension . 2018;71:e13– e115. 32. Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation . 2019;140:e596–e646. 33. Gulati M, Levy PD, Mukherjee D, et al. 2021 AHA/ACC/ASE/CHEST/ SAEM/SCCT/SCMR guideline for the evaluation and diagnosis of chest pain: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation . 2021;144:e368–e454. 34. Kleindorfer DO, Towfighi A, Chaturvedi S, et al. 2021 Guideline for the pre vention of stroke in patients with stroke and transient ischemic attack: a guideline from the American Heart Association/American Stroke Associa tion. Stroke . 2021;52:e364–e467. 35. Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA guide line for the management of heart failure: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Prac tice Guidelines. Circulation . 2022;145:e895–e1032. 36. Virani SS, Newby LK, Arnold SV, et al. 2023 AHA/ACC/ACCP/ASPC/ NLA/PCNA guideline for the management of patients with chronic coro nary disease: a report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines. Circulation . 2023;148:e9–e119. 37. Joglar JA, Chung MK, Armbruster AL, et al. 2023 ACC/AHA/ACCP/HRS guideline for the diagnosis and management of atrial fibrillation: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation . 2024;149:e1–e156. 38. Thomas RJ, Beatty AL, Beckie TM, et al. Home-based cardiac rehabilitation: a scientific statement from the American Association of Cardiovascular and Pulmonary Rehabilitation, the American Heart Association, and the Ameri can College of Cardiology. Circulation . 2019;140:e69–e89. 39. Baran DA, Grines CL, Bailey S, et al. SCAI clinical expert consensus state ment on the classification of cardiogenic shock. Catheter Cardiovasc Interv . 2019;94:29–37. 40. Tamis-Holland JE, Jneid H, Reynolds HR, et al. Contemporary diagnosis and management of patients with myocardial infarction in the absence of ob structive coronary artery disease: a scientific statement from the American Heart Association. Circulation . 2019;139:e891–e908. 41. Henry TD, Tomey MI, Tamis-Holland JE, et al. Invasive management of acute myocardial infarction complicated by cardiogenic shock: a scientific state ment from the American Heart Association. Circulation . 2021;143:e815– e829. 42. Damluji AA, van Diepen S, Katz JN, et al. Mechanical complications of acute myocardial infarction: a scientific statement from the American Heart As sociation. Circulation . 2021;144:e16–e35. 43. Naidu SS, Baran DA, Jentzer JC, et al. SCAI SHOCK stage classification expert consensus update: a review and incorporation of validation studies. J Am Coll Cardiol . 2022;79:933–946. 44. Levine GN, McEvoy JW, Fang JC, et al. Management of patients at risk for and with left ventricular thrombus: a scientific statement from the American Heart Association. Circulation . 2022;146:e205–e223. 45. Tamis-Holland JE, Menon V, Johnson NJ, et al. Cardiac catheterization labo ratory management of the comatose adult patient with an out-of-hospital cardiac arrest: a scientific statement from the American Heart Association. Circulation . 2024;149:e274–e295.

1.5. Class of Recommendation and Level of Evidence

1. ACCF/AHA Task Force on Practice Guidelines. Methodology Manual and Policies From the ACCF/AHA Task Force on Practice Guidelines. American College of Cardiology and American Heart Association. 2010. Accessed June 3, 2024. https://www.acc.org/-/media/Non-Clinical/Files-PDFs-Excel-MS-Word-etc/Guidelines/About-Guidelines-and-Clinical-Documents/Methodology/2014/Methodology-Practice-Guidelines.pd f?la=en&hash=157B7835091CF7856B26528717BE14B33BE822 6F and https://professional.heart.org/-/media/phd-files/guidelines-and-statements/methodology_manual_and_policies_ucm_319826.pdf.

2.1. Definition and Classification of ACS

1. Libby P. Mechanisms of acute coronary syndromes and their implications for therapy. N Engl J Med . 2013;368:2004–2013. 2. Falk E, Nakano M, Bentzon JF, et al. Update on acute coronary syndromes: the pathologists’ view. Eur Heart J . 2013;34:719–728. 3. Bhatt DL, Lopes RD, Harrington RA. Diagnosis and treatment of acute coronary syndromes: a review. JAMA . 2022;327:662–675. 4. Thygesen K, Alpert JS, Jaffe AS, et al. Fourth universal definition of myocar dial infarction (2018). J Am Coll Cardiol . 2018;72:2231–2264. 5. Gulati M, Levy PD, Mukherjee D, et al. 2021 AHA/ACC/ASE/CHEST/ SAEM/SCCT/SCMR guideline for the evaluation and diagnosis of chest pain: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation . 2021;144:e368–e454. 6. Hayes SN, Kim ESH, Saw J, et al. Spontaneous coronary artery dissection: current state of the science: a scientific statement from the American Heart Association. Circulation . 2018;137:e523–e557. 7. Tamis-Holland JE, Jneid H, Reynolds HR, et al. Contemporary diagnosis and management of patients with myocardial infarction in the absence of ob structive coronary artery disease: a scientific statement from the American Heart Association. Circulation . 2019;139:e891–e908. 8. DeFilippis AP, Chapman AR, Mills NL, et al. Assessment and treatment of patients with type 2 myocardial infarction and acute nonischemic myocar dial injury. Circulation . 2019;140:1661–1678. 9. Jernberg T, Hasvold P, Henriksson M, et al. Cardiovascular risk in postmyocardial infarction patients: nationwide real world data demonstrate the importance of a long-term perspective. Eur Heart J . 2015;36:1163–1170. 10. Virani SS, Newby LK, Arnold SV, et al. 2023 AHA/ACC/ACCP/ASPC/ NLA/PCNA guideline for the management of patients with chronic coro nary disease: a report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines. Circulation . 2023;148:e9–e119. 11. Kontos MC, de Lemos JA, Deitelzweig SB, et al. 2022 ACC expert consen sus decision pathway on the evaluation and disposition of acute chest pain in the emergency department: a report of the American College of Cardiol ogy Solution Set Oversight Committee. J Am Coll Cardiol . 2022;80:1925– 1960. 12. Wang K, Asinger RW, Marriott HJ. ST-segment elevation in conditions other than acute myocardial infarction. N Engl J Med 2003;349:2128–2135. 13. Birnbaum Y, Ye Y, Smith SW, Jneid H. Rapid diagnosis of stemi equivalent in patients with left bundle-branch block: Is it feasible? J Am Heart Assoc 2021;10:e023275.

3.1.1. Prehospital Assessment and Management Consid erations for Suspected ACS

1. Nakashima T, Hashiba K, Kikuchi M, et al. Impact of prehospital 12-lead electrocardiography and destination hospital notification on mortality in pa tients with chest pain- a systematic review. Circ Rep . 2022;4:187–193. 2. Quinn T, Johnsen S, Gale CP, et al. Effects of prehospital 12-lead ECG on processes of care and mortality in acute coronary syndrome: a linked cohort study from the Myocardial Ischaemia National Audit Project. Heart . 2014;100:944–950. 3. Verbeek PR, Ryan D, Turner L, Craig AM. Serial prehospital 12-lead elec trocardiograms increase identification of ST-segment elevation myocardial infarction. Prehosp Emerg Care . 2012;16:109–114. 4. Tanguay A, Lebon J, Lau L, et al. Detection of STEMI using prehospital serial 12-lead electrocardiograms. Prehosp Emerg Care . 2018;22:419–426. 5. Rokos IC, French WJ, Koenig WJ, et al. Integration of pre-hospital electro cardiograms and ST-elevation myocardial infarction receiving center (SRC) networks: impact on door-to-balloon times across 10 independent regions. J Am Coll Cardiol Intv . 2009;2:339–346. 6. Sorensen JT, Terkelsen CJ, Norgaard BL, et al. Urban and rural implementa tion of pre-hospital diagnosis and direct referral for primary percutaneous coronary intervention in patients with acute ST-elevation myocardial infarc tion. Eur Heart J . 2011;32:430–436. 7. Le May MR, Wells GA, So DY, et al. Reduction in mortality as a result of direct transport from the field to a receiving center for primary percutaneous coronary intervention. J Am Coll Cardiol . 2012;60:1223–1230. 8. Nam J, Caners K, Bowen JM, et al. Systematic review and meta-analysis of the benefits of out-of-hospital 12-lead ECG and advance notification in ST-segment elevation myocardial infarction patients. Ann Emerg Med . 2014;64:176-186, 186.e171–179. 9. Shavadia JS, Roe MT, Chen AY, et al. Association between cardiac cath eterization laboratory pre-activation and reperfusion timing metrics and out comes in patients with ST-segment elevation myocardial infarction undergo ing primary percutaneous coronary intervention: a report from the ACTION registry. JACC Cardiovasc Interv . 2018;11:1837–1847. 10. Gulati M, Levy PD, Mukherjee D, et al. 2021 AHA/ACC/ASE/CHEST/ SAEM/SCCT/SCMR guideline for the evaluation and diagnosis of chest pain: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation . 2021;144:e368–e454. 11. Jollis JG, Al-Khalidi HR, Roettig ML, et al. Impact of regionalization of STsegment-elevation myocardial infarction care on treatment times and out comes for emergency medical services: transported patients presenting to hospitals with percutaneous coronary intervention: Mission: Lifeline Accel erator-2. Circulation . 2018;137:376–387. 12. Mathews R, Peterson ED, Li S, et al. Use of emergency medical service transport among patients with ST-segment-elevation myocardial infarction: findings from the National Cardiovascular Data Registry Acute Coronary Treatment Intervention Outcomes Network Registry-Get With The Guide lines. Circulation . 2011;124:154–163. 13. Becker L, Larsen MP, Eisenberg MS. Incidence of cardiac arrest during selftransport for chest pain. Ann Emerg Med . 1996;28:612–616. 14. Herlitz J, Hansson E, Ringvall E, et al. Predicting a life-threatening disease and death among ambulance-transported patients with chest pain or other symptoms raising suspicion of an acute coronary syndrome. Am J Emerg Med . 2002;20:588–594. 15. Rosell-Ortiz F, Mellado-Vergel FJ, Fernandez-Valle P, et al. Initial complica tions and factors related to prehospital mortality in acute myocardial infarc tion with ST segment elevation. Emerg Med J . 2015;32:559–563. 16. Le May MR, So DY, Dionne R, et al. A citywide protocol for primary PCI in ST-segment elevation myocardial infarction. N Engl J Med . 2008;358:231– 240. 17. Tanaka A, Matsuo K, Kikuchi M, et al. Systematic review and meta-anal ysis of diagnostic accuracy to identify ST-segment elevation myocardial infarction on interpretations of prehospital electrocardiograms. Circ Rep . 2022;4:289–297. 18. Keeley E, Boura, JA, Grines, CL. Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review of 23 randomised trials. Lancet 2003;361:13–20. 19. De Luca G, Suryapranata H, Ottervanger JP, Antman EM. Time delay to treatment and mortality in primary angioplasty for acute myocardial infarc tion: every minute of delay counts. Circulation . 2004;109:1223–1225. 20. McNamara RL, Wang Y, Herrin J, et al. Effect of door-to-balloon time on mortality in patients with ST-segment elevation myocardial infarction. J Am Coll Cardiol . 2006;47:2180–2186. 21. De Luca G, Biondi-Zoccai G, Marino P. Transferring patients with ST-seg ment elevation myocardial infarction for mechanical reperfusion: a meta-re gression analysis of randomized trials. Ann Emerg Med . 2008;52:665–676. 22. Andersen HR, Nielsen TT, Rasmussen K, et al. A comparison of coronary angioplasty with fibrinolytic therapy in acute myocardial infarction. N Engl J Med . 2003;349:733–742. 23. Widimsky P, Budesinsky T, Vorac D, et al. Long distance transport for primary angioplasty vs immediate thrombolysis in acute myocardial infarction. Final results of the randomized national multicentre trial PRAGUE-2. Eur Heart J . 2003;24:94–104. 24. Fordyce CB, Al-Khalidi HR, Jollis JG, et al. Association of rapid care process implementation on reperfusion times across multiple ST-segment-elevation myocardial infarction networks. Circ Cardiovasc Interv . 2017;10:e004061. 25. Savage ML, Poon KK, Johnston EM, et al. Pre-hospital ambulance notifica tion and initiation of treatment of ST elevation myocardial infarction is as sociated with significant reduction in door-to-balloon time for primary PCI. Heart Lung Circ . 2014;23:435–443.

3.1.2. Initial In-Hospital Assessment of Patients With Confirmed or Suspected ACS

1. Diercks DB, Peacock WF, Hiestand BC, et al. Frequency and consequences of recording an electrocardiogram ${>}10$ minutes after arrival in an emer gency room in non-ST-segment elevation acute coronary syndromes (from the CRUSADE Initiative). Am J Cardiol . 2006;97:437–442. 2. Diercks DB, Kontos MC, Chen AY, et al. Utilization and impact of prehospital electrocardiograms for patients with acute ST-segment elevation myocardial infarction: data from the NCDR (National Cardiovascular Data Registry) ACTION (Acute Coronary Treatment and Intervention Outcomes Network) Registry. J Am Coll Cardiol . 2009;53:161–166. 3. Riley RF, Newby LK, Don CW, et al. Diagnostic time course, treatment, and in-hospital outcomes for patients with ST-segment elevation myocardial infarction presenting with nondiagnostic initial electrocardiogram: a report from the American Heart Association Mission: Lifeline program. Am Heart J . 2013;165:50–56. 4. Lipinski MJ, Baker NC, Escarcega RO, et al. Comparison of conventional and high-sensitivity troponin in patients with chest pain: a collaborative meta-analysis. Am Heart J . 2015;169:6–16.e16. 5. Anand A, Lee KK, Chapman AR, et al. High-sensitivity cardiac troponin on presentation to rule out myocardial infarction: a stepped-wedge cluster ran domized controlled trial. Circulation . 2021;143:2214–2224. 6. Shah ASV, Anand A, Strachan FE, et al. High-sensitivity troponin in the evaluation of patients with suspected acute coronary syndrome: a steppedwedge, cluster-randomised controlled trial. Lancet . 2018;392:919–928. 7. Reichlin T, Hochholzer W, Bassetti S, et al. Early diagnosis of myocar dial infarction with sensitive cardiac troponin assays. N Engl J Med . 2009;361:858–867. 8. Chew DP, Lambrakis K, Blyth A, et al. A randomized trial of a 1-hour tro ponin T protocol in suspected acute coronary syndromes: the Rapid As sessment of Possible Acute Coronary Syndrome in the Emergency De partment With High-Sensitivity Troponin T Study (RAPID-TnT). Circulation . 2019;140:1543–1556. 9. Neumann JT, Sorensen NA, Rubsamen N, et al. Evaluation of a new ultrasensitivity troponin I assay in patients with suspected myocardial infarction. Int J Cardiol . 2019;283:35–40. 10. Boeddinghaus J, Nestelberger T, Twerenbold R, et al. Direct comparison of 4 very early rule-out strategies for acute myocardial infarction using highsensitivity cardiac troponin I. Circulation . 2017;135:1597–1611. 11. Twerenbold R, Costabel JP, Nestelberger T, et al. Outcome of applying the ESC 0/1-hour algorithm in patients with suspected myocardial infarction. J Am Coll Cardiol . 2019;74:483–494. 12. Badertscher P, Boeddinghaus J, Twerenbold R, et al. Direct comparison of the 0/1h and 0/3h algorithms for early rule-out of acute myocardial infarc tion. Circulation . 2018;137:2536–2538. 13. Gulati M, Levy PD, Mukherjee D, et al. 2021 AHA/ACC/ASE/CHEST/ SAEM/SCCT/SCMR guideline for the evaluation and diagnosis of chest pain: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation . 2021;144:e368–e454. 14. National Center for Health Statistics. Emergency Department Visits in the United States, 2016-2021. Accessed August 6, 2023. https://www.cdc. gov/nchs/dhcs/ed-visits/index.htm. 15. Thygesen K, Alpert JS, Jaffe AS, et al. Fourth universal definition of myocar dial infarction (2018). Eur Heart J . 2019;40:237–269. 16. Mahler SA, Riley RF, Hiestand BC, et al. The HEART Pathway randomized trial: identifying emergency department patients with acute chest pain for early discharge. Circ Cardiovasc Qual Outcomes . 2015;8:195–203. 17. Than MP, Pickering JW, Aldous SJ, et al. Effectiveness of EDACS ver sus ADAPT accelerated diagnostic pathways for chest pain: a pragmatic randomized controlled trial embedded within practice. Ann Emerg Med . 2016;68:93–102.e101. 18. Twerenbold R, Neumann JT, Sorensen NA, et al. Prospective validation of the 0/1-h Algorithm for early diagnosis of myocardial infarction. J Am Coll Cardiol . 2018;72:620–632. 19. Mark DG, Huang J, Chettipally U, et al. Performance of coronary risk scores among patients with chest pain in the emergency department. J Am Coll Cardiol . 2018;71:606–616. 20. Puymirat E, Simon T, Steg PG, et al. Association of changes in clinical char acteristics and management with improvement in survival among patients with ST-elevation myocardial infarction. JAMA . 2012;308:998–1006. 21. Thygesen K, Alpert JS, Jaffe AS, et al. Fourth universal definition of myocar dial infarction (2018). Circulation . 2018;138:e618–e651. 22. Lopez-Sendon J, Coma-Canella I, Alcasena S, et al. Electrocardiographic findings in acute right ventricular infarction: sensitivity and specificity of electrocardiographic alterations in right precordial leads V4R, V3R, V1, V2, and V3. J Am Coll Cardiol . 1985;6:1273–1279. 23. Apple FS, Wu AH, Jaffe AS, et al. National Academy of Clinical Biochemistry and IFCC Committee for Standardization of Markers of Cardiac Damage Laboratory Medicine practice guidelines: analytical issues for biomarkers of heart failure. Circulation . 2007;116:e95–e98. 24. Morrow DA, Cannon CP, Jesse RL, et al. National Academy of Clinical Bio chemistry Laboratory Medicine practice guidelines: clinical characteristics and utilization of biochemical markers in acute coronary syndromes. Circula tion . 2007;115:e356–e375. 25. Cullen L, Mueller C, Parsonage WA, et al. Validation of high-sensitivity tro ponin I in a 2-hour diagnostic strategy to assess 30-day outcomes in emer gency department patients with possible acute coronary syndrome. J Am Coll Cardiol . 2013;62:1242–1249. 26. Twerenbold R, Badertscher P, Boeddinghaus J, et al. Effect of the FDA regulatory approach on the 0/1-h algorithm for rapid diagnosis of MI. J Am Coll Cardiol . 2017;70:1532–1534. 27. Chiang CH, Chiang CH, Lee GH, et al. Safety and efficacy of the European Society of Cardiology 0/1-hour algorithm for diagnosis of myocardial infarc tion: systematic review and meta-analysis. Heart . 2020;106:985–991. 28. Reichlin T, Schindler C, Drexler B, et al. One-hour rule-out and rule-in of acute myocardial infarction using high-sensitivity cardiac troponin T. Arch Intern Med . 2012;172:1211–1218. 29. Allen BR, Christenson RH, Cohen SA, et al. Diagnostic performance of highsensitivity cardiac troponin T strategies and clinical variables in a multisite US cohort. Circulation . 2021;143:1659–1672. 30. Karady J, Morrow DA. Critical appraisal of the negative predictive perfor mance of the European Society of Cardiology 0/1-hour algorithm for evalu ating patients with chest pain in the US. JAMA Cardiol . 2023;8:314–316. 31. Keller T, Zeller T, Peetz D, et al. Sensitive troponin I assay in early diagnosis of acute myocardial infarction. N Engl J Med . 2009;361:868–877. 32. Sandoval Y, Apple FS, Mahler SA, et al. High-sensitivity cardiac troponin and the 2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR guide lines for the evaluation and diagnosis of acute chest pain. Circulation . 2022;146:569–581.

3.1.3. Risk Stratification Tools for Patients With STEMI and NSTE-ACS

1. Brilakis ES, Wright RS, Kopecky SL, et al. Association of the PURSUIT risk score with predischarge ejection fraction, angiographic severity of coronary artery disease, and mortality in a nonselected, community-based population with non-ST-elevation acute myocardial infarction. Am Heart J . 2003;146:811–818. 2. Backus BE, Six AJ, Kelder JH, et al. Risk scores for patients with chest pain: evaluation in the emergency department. Curr Cardiol Rev . 2011;7:2–8. 3. Gale CP, Manda SO, Weston CF, et al. Evaluation of risk scores for risk stratification of acute coronary syndromes in the Myocardial Infarction Na tional Audit Project (MINAP) database. Heart . 2009;95:221–227. 4. Antman EM, Cohen M, Bernink PJ, et al. The TIMI risk score for unstable angina/non-ST elevation MI: a method for prognostication and therapeutic decision making. JAMA . 2000;284:835–842. 5. Morrow DA, Antman EM, Charlesworth A, et al. TIMI risk score for ST-el evation myocardial infarction: a convenient, bedside, clinical score for risk assessment at presentation: an intravenous nPA for treatment of infarcting myocardium early II trial substudy. Circulation . 2000;102:2031–2037. 6. Fox KA, Dabbous OH, Goldberg RJ, et al. Prediction of risk of death and myocardial infarction in the six months after presentation with acute coro nary syndrome: prospective multinational observational study (GRACE). BMJ . 2006;333:1091. 7. Fox KA, Fitzgerald G, Puymirat E, et al. Should patients with acute coronary disease be stratified for management according to their risk? Derivation, ex ternal validation and outcomes using the updated GRACE risk score. BMJ Open . 2014;4:e004425. 8. Chew DP, Junbo G, Parsonage W, et al. Perceived risk of ischemic and bleeding events in acute coronary syndromes. Circ Cardiovasc Qual Out comes . 2013;6:299–308. 9. Chew DP, Hyun K, Morton E, et al. Objective risk assessment vs standard care for acute coronary syndromes: a randomized clinical trial. JAMA Cardiol . 2021;6:304–313. 10. Gale CP, Stocken DD, Aktaa S, et al. Effectiveness of GRACE risk score in patients admitted to hospital with non-ST elevation acute coronary syn drome (UKGRIS): parallel group cluster randomised controlled trial. BMJ . 2023;381:e073843. 11. Killip TIII, Kimball JT. Treatment of myocardial infarction in a coronary care unit. A two year experience with 250 patients. Am J Cardiol . 1967;20:457– 464. 12. Araujo GN, Silveira AD, Scolari FL, et al. Admission bedside lung ultrasound reclassifies mortality prediction in patients with ST-segment-elevation myo cardial infarction. Circ Cardiovasc Imaging . 2020;13:e010269. 13. Lindner M, Lindsey A, Bain PA, et al. Prevalence and prognostic importance of lung ultrasound findings in acute coronary syndrome: a systematic review. Echocardiography . 2021;38:2069–2076. 14. van Diepen S, Chen AY, Wang TY, et al. Influence of heart failure symp toms and ejection fraction on short- and long-term outcomes for older patients with non-ST-segment elevation myocardial infarction. Am Heart J . 2014;167:267–273.e261. 15. Lewis EF, Velazquez EJ, Solomon SD, et al. Predictors of the first heart failure hospitalization in patients who are stable survivors of myocardial in farction complicated by pulmonary congestion and/or left ventricular dys function: a VALIANT study. Eur Heart J . 2008;29:748–756. 16. Neumann JT, Twerenbold R, Ojeda F, et al. Application of High-sensitivity tro ponin in suspected myocardial infarction. N Engl J Med . 2019;380:2529– 2540. 17. Aviles RJ, Askari AT, Lindahl B, et al. Troponin T levels in patients with acute coronary syndromes, with or without renal dysfunction. N Engl J Med . 2002;346:2047–2052. 18. Morrow DA, Cannon CP, Rifai N, et al. Ability of minor elevations of troponins I and T to predict benefit from an early invasive strategy in patients with unstable angina and non-ST elevation myocardial infarction: results from a randomized trial. JAMA . 2001;286:2405–2412. 19. Scirica BM, Sabatine MS, Jarolim P, et al. Assessment of multiple cardiac biomarkers in non-ST-segment elevation acute coronary syndromes: obser vations from the MERLIN-TIMI 36 trial. Eur Heart J . 2011;32:697–705. 20. Jering KS, Claggett BL, Pfeffer MA, et al. Prognostic importance of NT-proB NP (N-terminal pro-B-type natriuretic peptide) following high-risk myocar dial infarction in the PARADISE-MI trial. Circ Heart Fail . 2023;16:e010259. 21. Rab T, Ratanapo S, Kern KB, et al. Cardiac shock care centers: JACC review topic of the week. J Am Coll Cardiol . 2018;72:1972–1980. 22. Henry TD, Tomey MI, Tamis-Holland JE, et al. Invasive management of acute myocardial infarction complicated by cardiogenic shock: a scientific state ment from the American Heart Association. Circulation . 2021;143:e815– e829. 23. Naidu SS, Baran DA, Jentzer JC, et al. SCAI SHOCK stage classification expert consensus update: a review and incorporation of validation studies. J Am Coll Cardiol . 2022;79:933–946.

3.2. Management of Patients Presenting With Cardiac Arrest

1. Wnent J, Seewald S, Heringlake M, et al. Choice of hospital after out-ofhospital cardiac arrest-a decision with far-reaching consequences: a study in a large German city. Crit Care . 2012;16:R164. 2. Kragholm K, Malta Hansen C, Dupre ME, et al. Direct transport to a percu taneous cardiac intervention center and outcomes in patients with out-ofhospital cardiac arrest. Circ Cardiovasc Qual Outcomes . 2017;10:e003414. 3. Gorjup V, Radsel P, Kocjancic ST, et al. Acute ST-elevation myocardial in farction after successful cardiopulmonary resuscitation. Resuscitation . 2007;72:379–385. 4. Pareek N, Beckley-Hoelscher N, Kanyal R, et al. MIRACLE(2) score and SCAI grade to identify patients with out-of-hospital cardiac arrest for im mediate coronary angiography. J Am Coll Cardiol Intv . 2022;15:1074–1084. 5. Garot P, Lefevre T, Eltchaninoff H, et al. Six-month outcome of emer gency percutaneous coronary intervention in resuscitated patients after cardiac arrest complicating ST-elevation myocardial infarction. Circulation . 2007;115:1354–1362. 6. Hosmane VR, Mustafa NG, Reddy VK, et al. Survival and neurologic recov ery in patients with ST-segment elevation myocardial infarction resuscitated from cardiac arrest. J Am Coll Cardiol . 2009;53:409–415. 7. Bougouin W, Dumas F, Karam N, et al. Should we perform an immediate coronary angiogram in all patients after cardiac arrest?: Insights from a large French registry. J Am Coll Cardiol Intv . 2018;11:249–256. 8. Lemkes JS, Janssens GN, van der Hoeven NW, et al. Coronary angiography after cardiac arrest without ST segment elevation: one-year outcomes of the COACT randomized clinical trial. JAMA Cardiol . 2020;5:1358–1365. 9. Kern KB, Radsel P, Jentzer JC, et al. Randomized pilot clinical trial of early coronary angiography versus no early coronary angiography after car diac arrest without ST-segment elevation: the PEARL study. Circulation . 2020;142:2002–2012. 10. Desch S, Freund A, Akin I, et al. Angiography after out-of-hospital cardi ac arrest without ST-segment elevation. N Engl J Med . 2021;385:2544– 2553. 11. Hauw-Berlemont C, Lamhaut L, Diehl J-L, et al. Emergency vs delayed coronary angiogram in survivors of out-of-hospital cardiac arrest: results of the randomized, multicentric EMERGE trial. JAMA Cardiol . 2022;7:700– 707. 12. Elfwen L, Lagedal R, Nordberg P, et al. Direct or subacute coronary angi ography in out-of-hospital cardiac arrest (DISCO)-An initial pilot-study of a randomized clinical trial. Resuscitation . 2019;139:253–261. 13. Viana-Tejedor A, Andrea-Riba R, Scardino C, et al. Coronary angiography in patients without ST-segment elevation following out-of-hospital cardiac arrest. COUPE clinical trial. Rev Esp Cardiol (Engl Ed) . 2023;76:94–102. 14. Lemkes JS, Janssens GN, van der Hoeven NW, et al. Coronary angiog raphy after cardiac arrest without ST-segment elevation. N Engl J Med . 2019;380:1397–1407. 15. Kragholm K, Lu D, Chiswell K, et al. Improvement in care and outcomes for emergency medical service-transported patients with ST-elevation myocar dial infarction (STEMI) with and without prehospital cardiac arrest: a Mis sion: Lifeline STEMI Accelerator study. J Am Heart Assoc . 2017;6:e005717. 16. Myat A, Song KJ, Rea T. Out-of-hospital cardiac arrest: current concepts. Lancet . 2018;391:970–979. 17. Kern KB, Lotun K, Patel N, et al. Outcomes of comatose cardiac ar rest survivors with and without ST-segment elevation myocardial in farction: importance of coronary angiography. J Am Coll Cardiol Intv . 2015;8:1031–1040. 18. Henry TD, Tomey MI, Tamis-Holland JE, et al. Invasive management of acute myocardial infarction complicated by cardiogenic shock: a scientific state ment from the American Heart Association. Circulation . 2021;143:e815– e829. 19. Tamis-Holland JE, Menon V, Johnson NJ, et al. Cardiac catheterization labo ratory management of the comatose adult patient with an out-of-hospital cardiac arrest: a scientific statement from the American Heart Association. Circulation . 2024;149:e274–e295. 20. Patterson T, Perkins GD, Perkins A, et al. Expedited transfer to a cardiac arrest centre for non-ST-elevation out-of-hospital cardiac arrest (ARREST): a UK prospective, multicentre, parallel, randomised clinical trial. Lancet . 2023;402:1329–1337. 21. Adrie C, Cariou A, Mourvillier B, et al. Predicting survival with good neurolog ical recovery at hospital admission after successful resuscitation of out-ofhospital cardiac arrest: the OHCA score. Eur Heart J . 2006;27:2840–2845. 22. Gue YX, Sayers M, Whitby BT, et al. Usefulness of the NULL-PLEASE score to predict survival in Out-of-Hospital Cardiac Arrest (OCHA). Am J Med . 2020;133:1328–1335. 23. Nishikimi M, Ogura T, Nishida K, et al. External validation of a risk clas sification at the emergency department of post-cardiac arrest syndrome patients undergoing targeted temperature management. Resuscitation . 2019;140:135–141. 24. Martinell L, Nielsen N, Herlitz J, et al. Early predictors of poor outcome after out-of-hospital cardiac arrest. Crit Care . 2017;21:96. 25. Rab T, Kern KB, Tamis-Holland JE, et al. Cardiac arrest. J Am Coll Cardiol . 2015;66:62–73. 26. Harhash AA, May TL, Hsu C-H, et al. Risk stratification among survivors of cardiac arrest considered for coronary angiography. J Am Coll Cardiol . 2021;77:360–371. 27. Maupain C, Bougouin W, Lamhaut L, et al. The CAHP (Cardiac Arrest Hos pital Prognosis) score: a tool for risk stratification after out-of-hospital car diac arrest. Eur Heart J . 2015;37:3222–3228. 28. Bougouin W, Dumas F, Karam N, et al. Should we perform an immediate coronary angiogram in all patients after cardiac arrest? J Am Coll Cardiol Intv . 2018;11:249–256. 29. Lotfi A, Klein LW, Hira RS, et al. SCAI expert consensus statement on out of hospital cardiac arrest. Catheter Cardiovasc Interv . 2020;96:844–861. 30. Byrne RA, Rossello X, Coughlan JJ, et al. 2023 ESC guidelines for the man agement of acute coronary syndromes. Eur Heart J . 2023;44:3720–3826. 31. Bavishi C, Trivedi V, Bhatt DL. Meta-analysis of early versus delayed or se lective coronary angiography in patients with out-of-hospital cardiac arrest without ST-elevation myocardial infarction. Am J Cardiol . 2022;175:180– 182.

4.1. Oxygen Therapy

1. Sukumalchantra Y, Levy S, Danzig R, et al. Correcting arterial hypoxemia by oxygen therapy in patients with acute myocardial infarction. Effect on ventilation and hemodynamics. Am J Cardiol . 1969;24:838–852. 2. Hofmann R, James SK, Jernberg T, et al. Oxygen therapy in suspected acute myocardial infarction. N Engl J Med . 2017;377:1240–1249. 3. Stub D, Smith K, Bernard S, et al. Air versus oxygen in ST-segment-elevation myocardial infarction. Circulation . 2015;131:2143–2150. 4. Khoshnood A, Carlsson M, Akbarzadeh M, et al. Effect of oxygen therapy on myocardial salvage in ST elevation myocardial infarction: the randomized SOCCER trial. Eur J Emerg Med . 2018;25:78–84. 5. Beasley R, Aldington S, Weatherall M, et al. Oxygen therapy in myocardial infarction: an historical perspective. J R Soc Med . 2007;100:130–133. 6. Stewart RAH, Jones P, Dicker B, et al. High flow oxygen and risk of mortality in patients with a suspected acute coronary syndrome: pragmatic, cluster randomised, crossover trial. BMJ (Clinical research ed) . 2021;372:n355– n355. 7. Chu DK, Kim LH, Young PJ, et al. Mortality and morbidity in acutely ill adults treated with liberal versus conservative oxygen therapy (IOTA): a systematic review and meta-analysis. Lancet . 2018;391:1693–1705. 8. Yu Y, Wang J, Wang Q, et al. Admission oxygen saturation and all-cause in-hospital mortality in acute myocardial infarction patients: data from the MIMIC-III database. Ann Transl Med . 2020;8:1371. 9. Hofmann R, Witt N, Lagerqvist B, et al. Oxygen therapy in ST-elevation myo cardial infarction. Eur Heart J . 2018;39:2730–2739. 10. James SK, Erlinge D, Herlitz J, et al. Effect of oxygen therapy on cardiovas cular outcomes in relation to baseline oxygen saturation. J Am Coll Cardiol Intv . 2020;13:502–513.

4.2. Analgesics

1. GISSI-3: effects of lisinopril and transdermal glyceryl trinitrate singly and together on 6-week mortality and ventricular function after acute myocar dial infarction. Gruppo Italiano per lo Studio della Sopravvivenza nell’infarto Miocardico. Lancet . 1994;343:1115–1122. 2. ISIS-4: a randomised factorial trial assessing early oral captopril, oral mono nitrate, and intravenous magnesium sulphate in 58050 patients with sus pected acute myocardial infarction. ISIS-4 (Fourth International Study of Infarct Survival) Collaborative Group. Lancet . 1995;345:669–685. 3. Shotan A, Brill Z, Matetzky S, et al. Pain scoring-a method for assess ing acute antianginal therapy comparison of the response to acute sublingual administration of an isosorbide dinitrate tablet, isosorbide dinitrate spray and nitroglycerin spray in unstable angina. Cardiology . 1998;89:163–169. 4. Bosson N, Isakson B, Morgan JA, et al. Safety and effectiveness of field nitroglycerin in patients with suspected ST elevation myocardial infarction. Prehosp Emerg Care . 2019;23:603–611. 5. Parodi G. Chest pain relief in patients with acute myocardial infarction. Eur Heart J Acute Cardiovasc Care . 2016;5:277–281. 6. Meine TJ, Roe MT, Chen AY, et al. Association of intravenous morphine use and outcomes in acute coronary syndromes: results from the CRUSADE Quality Improvement Initiative. Am Heart J . 2005;149:1043–1049. 7. Kubica J, Adamski P, Ostrowska M, et al. Morphine delays and attenuates ticagrelor exposure and action in patients with myocardial infarction: the randomized, double-blind, placebo-controlled IMPRESSION trial. Eur Heart J . 2016;37:245–252. 8. Ibrahim K, Shah R, Goli $\mathbb{R}\mathbb{R},$ et al. Fentanyl delays the platelet inhibition ef fects of oral ticagrelor: full report of the PACIFY randomized clinical trial. Thromb Haemost . 2018;118:1409–1418. 9. Hobl EL, Stimpfl T, Ebner J, et al. Morphine decreases clopidogrel concen trations and effects: a randomized, double-blind, placebo-controlled trial. J Am Coll Cardiol . 2014;63:630–635. 10. Thomas MR, Morton AC, Hossain R, et al. Morphine delays the onset of action of prasugrel in patients with prior history of ST-elevation myocardial infarction. Thromb Haemost . 2016;116:96–102. 11. Lapostolle F, van’t Hof AW, Hamm CW, et al. Morphine and ticagrelor in teraction in primary percutaneous coronary intervention in ST-segment el evation myocardial infarction: ATLANTIC-Morphine. Am J Cardiovasc Drugs . 2019;19:173–183. 12. Furtado RHM, Nicolau JC, Guo J, et al. Morphine and cardiovascular out comes among patients with non-ST-segment elevation acute coronary syn dromes undergoing coronary angiography. J Am Coll Cardiol . 2020;75:289– 300. 13. Batchelor R, Liu DH, Bloom J, et al. Association of periprocedural intra venous morphine use on clinical outcomes in ST-elevation myocardial infarction (STEMI) treated by primary percutaneous coronary interven tion: systematic review and meta-analysis. Catheter Cardiovasc Interv . 2020;96:76–88. 14. Lee SW, Kuo N, Hou SK, et al. Effects of morphine and P2Y inhibitor amongst patients with acute coronary syndrome: a meta-analysis of com parative studies. Am J Emerg Med . 2023;70:119–126. 15. Schmidt M, Lamberts M, Olsen AM, et al. Cardiovascular safety of nonaspirin non-steroidal anti-inflammatory drugs: review and position paper by the working group for Cardiovascular Pharmacotherapy of the European Society of Cardiology. Eur Heart J . 2016;37:1015–1023. 16. Schjerning Olsen AM, Fosbol EL, Lindhardsen J, et al. Duration of treatment with nonsteroidal anti-inflammatory drugs and impact on risk of death and recurrent myocardial infarction in patients with prior myocardial infarction: a nationwide cohort study. Circulation . 2011;123:2226–2235. 17. Gislason GH, Jacobsen S, Rasmussen JN, et al. Risk of death or reinfarc tion associated with the use of selective cyclooxygenase-2 inhibitors and nonselective nonsteroidal antiinflammatory drugs after acute myocardial infarction. Circulation . 2006;113:2906–2913. 18. Hippisley-Cox J, Coupland C. Risk of myocardial infarction in patients taking cyclo-oxygenase-2 inhibitors or conventional non-steroidal antiinflammatory drugs: population based nested case-control analysis. BMJ . 2005;330:1366. 19. Antman EM, Bennett JS, Daugherty A, et al. Use of nonsteroidal antiin flammatory drugs: an update for clinicians: a scientific statement from the American Heart Association. Circulation . 2007;115:1634–1642. 20. Doucet S, Malekianpour M, Theroux P, et al. Randomized trial compar ing intravenous nitroglycerin and heparin for treatment of unstable an gina secondary to restenosis after coronary artery angioplasty. Circulation . 2000;101:955–961. 21. Karlberg KE, Saldeen T, Wallin R, et al. Intravenous nitroglycerin reduces ischaemia in unstable angina pectoris: a double-blind placebo-controlled study. J Intern Med . 1998;243:25–31. 22. Perez MI, Musini VM, Wright JM. Effect of early treatment with anti-hyper tensive drugs on short and long-term mortality in patients with an acute cardiovascular event. Cochrane Database Syst Rev . 2009;CD006743. 23. Kloner RA, Hutter AM, Emmick JT, et al. Time course of the interaction between tadalafil and nitrates. J Am Coll Cardiol . 2003;42:1855–1860. 24. Parker JD, Bart BA, Webb DJ, et al. Safety of intravenous nitroglycerin after administration of sildenafil citrate to men with coronary artery disease: a double-blind, placebo-controlled, randomized, crossover trial. Crit Care Med . 2007;35:1863–1868. 25. Swearingen D, Nehra A, Morelos S, et al. Hemodynamic effect of avanafil and glyceryl trinitrate coadministration. Drugs Context . 2013;2013:212248.

4.3.1. Aspirin

1. Antithrombotic Trialists Collaboration. Collaborative meta-analysis of ran domised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ . 2002;324:71–86. 2. Baigent C, Blackwell L, Collins R, et al. Antithrombotic Trialists Collabora tion. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet . 2009;373:1849–1860. 3. ISIS-2 (Second International Study of Infarct Survival) Collaborative Group. Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17187 cases of suspected acute myocardial infarction: ISIS-2. Lan cet . 1988;2:349–360. 4. Mehta SR, Bassand JP, Chrolavicius $S,$ et al. Current Oasis Investigators. Dose comparisons of clopidogrel and aspirin in acute coronary syndromes. N Engl J Med . 2010;363:930–942. 5. Jones WS, Mulder H, Wruck LM, et al. Comparative effectiveness of aspirin dosing in cardiovascular disease. N Engl J Med . 2021;384:1981–1990. 6. Antiplatelet Trialists’ Collaboration. Collaborative overview of randomised trials of antiplatelet therapy: prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients. BMJ . 1994;308:81–106. 7. Gollapudi RR, Teirstein PS, Stevenson DD, Simon RA. Aspirin sensitivity: im plications for patients with coronary artery disease. JAMA . 2004;292:3017– 3023. 8. Cortellini G, Raiteri A, Galli M, et al. Acetylsalicylic acid challenge or desen sitization in sensitive patients with cardiovascular disease. J Thromb Throm bolysis . 2023;55:762–769. 9. Chopra AM, Diez-Villanueva P, Cordoba-Soriano JG, et al. Meta-analysis of acetylsalicylic acid desensitization in patients with acute coronary syndrome. Am J Cardiol . 2019;124:14–19. 10. Patrono C, Garcia Rodriguez LA, Landolfi R, et al. Low-dose aspirin for the prevention of atherothrombosis. N Engl J Med . 2005;353:2373–2383. 11. Mahaffey KW, Wojdyla DM, Carroll K, et al. Ticagrelor compared with clopi dogrel by geographic region in the Platelet Inhibition and Patient Outcomes (PLATO) trial. Circulation . 2011;124:544–554.

4.3.2. Oral P2Y12 Inhibitors During Hospitalization

1. Yusuf S, Zhao F, Mehta SR, et al. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med . 2001;345:494–502. 2. Sabatine MS, Cannon CP, Gibson CM, et al. Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial infarction with ST-segment elevation. N Engl J Med . 2005;352:1179–1189. 3. Chen ZM, Jiang LX, Chen YP, et al. Addition of clopidogrel to aspirin in 45852 patients with acute myocardial infarction: randomised placebo-con trolled trial. Lancet . 2005;366:1607–1621. 4. Wiviott SD, Braunwald E, McCabe CH, et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med . 2007;357:2001– 2015. 5. Wallentin L, Becker RC, Budaj A, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med . 2009;361:1045– 1057. 6. Cannon CP, Harrington RA, James S, et al. Comparison of ticagrelor with clopidogrel in patients with a planned invasive strategy for acute coronary syndromes (PLATO): a randomised double-blind study. Lancet . 2010;375:283–293. 7. James SK, Roe MT, Cannon CP, et al. Ticagrelor versus clopidogrel in pa tients with acute coronary syndromes intended for non-invasive manage ment: substudy from prospective randomised PLATelet inhibition and pa tient Outcomes (PLATO) trial. BMJ . 2011;342:d3527. 8. Mehta SR, Yusuf S, Peters RJ, et al. Effects of pretreatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percuta neous coronary intervention: the PCI-CURE study. Lancet . 2001;358:527– 533. 9. Montalescot G, Wiviott SD, Braunwald E, et al. Prasugrel compared with clopidogrel in patients undergoing percutaneous coronary intervention for ST-elevation myocardial infarction (TRITON-TIMI 38): double-blind, ran domised controlled trial. Lancet . 2009;373:723–731. 10. Steg PG, James S, Harrington RA, et al. Ticagrelor versus clopidogrel in patients with ST-elevation acute coronary syndromes intended for reper fusion with primary percutaneous coronary intervention: a Platelet Inhibi tion and Patient Outcomes (PLATO) trial subgroup analysis. Circulation . 2010;122:2131–2141. 11. Sabatine MS, Cannon CP, Gibson CM, et al. Effect of clopidogrel pretreat ment before percutaneous coronary intervention in patients with ST-eleva tion myocardial infarction treated with fibrinolytics: the PCI-CLARITY study. JAMA . 2005;294:1224–1232. 12. Lawton JS, Tamis-Holland JE, Bangalore S, et al. 2021 ACC/AHA/SCAI guideline for coronary artery revascularization: a report of the American Col lege of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation . 2022;145:e18–e114. 13. Virani SS, Newby LK, Arnold SV, et al. 2023 AHA/ACC/ACCP/ASPC/ NLA/PCNA guideline for the management of patients with chronic coro nary disease: a report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines. Circulation . 2023;148:e9–e119. 14. O’Donoghue M, Wiviott SD. Clopidogrel response variability and future therapies: clopidogrel: does one size fit all? Circulation . 2006;114:e600– e606. 15. Gurbel PA, Bliden KP, Hiatt BL, O’Connor CM. Clopidogrel for coronary stenting: response variability, drug resistance, and the effect of pretreat ment platelet reactivity. Circulation . 2003;107:2908–2913. 16. Mega JL, Close SL, Wiviott SD, et al. Cytochrome p-450 polymorphisms and response to clopidogrel. N Engl J Med . 2009;360:354–362. 17. Simon T, Verstuyft C, Mary-Krause M, et al. Genetic determinants of response to clopidogrel and cardiovascular events. N Engl J Med . 2009;360:363– 375. 18. Fox KA, Mehta SR, Peters R, et al. Benefits and risks of the combination of clopidogrel and aspirin in patients undergoing surgical revascularization for non-ST-elevation acute coronary syndrome: the Clopidogrel in Unsta ble angina to prevent Recurrent ischemic Events (CURE) Trial. Circulation . 2004;110:1202–1208. 19. Held C, Asenblad N, Bassand JP, et al. Ticagrelor versus clopidogrel in pa tients with acute coronary syndromes undergoing coronary artery bypass surgery: results from the PLATO (Platelet Inhibition and Patient Outcomes) trial. J Am Coll Cardiol . 2011;57:672–684. 20. Smith PK, Goodnough LT, Levy JH, et al. Mortality benefit with prasugrel in the TRITON-TIMI 38 coronary artery bypass grafting cohort: risk-adjusted retrospective data analysis. J Am Coll Cardiol . 2012;60:388–396. 21. Zhao Q, Zhu Y, Xu Z, et al. Effect of Ticagrelor Plus Aspirin, Ticagrelor Alone, or Aspirin Alone on Saphenous Vein Graft Patency 1 Year After Coronary Artery Bypass Grafting: a randomized clinical trial. JAMA . 2018;319:1677– 1686. 22. Schupke S, Neumann FJ, Menichelli M, et al. Ticagrelor or prasugrel in patients with acute coronary syndromes. N Engl J Med . 2019;381:1524– 1534. 23. Gimbel M, Qaderdan K, Willemsen L, et al. Clopidogrel versus ticagrelor or prasugrel in patients aged 70 years or older with non-ST-elevation acute coronary syndrome (POPular AGE): the randomised, open-label, non-inferi ority trial. Lancet . 2020;395:1374–1381. 24. Montalescot G, Bolognese L, Dudek D, et al. Pretreatment with prasug rel in non-ST-segment elevation acute coronary syndromes. N Engl J Med . 2013;369:999–1010. 25. Montalescot G, Van’t Hof AW, Lapostolle F, et al. Prehospital ticagrelor in STsegment elevation myocardial infarction. N Engl J Med . 2014;371:1016– 1027. 26. Rohla M, Ye SX, Shibutani H, et al. Pretreatment with P2Y(12) inhibitors in ST-segment elevation myocardial infarction: insights from the Bern-PCI registry. JACC Cardiovasc Interv . 2024;17:17–28. 27. Bellemain-Appaix A, O’Connor SA, Silvain J, et al. Association of clopido grel pretreatment with mortality, cardiovascular events, and major bleeding among patients undergoing percutaneous coronary intervention: a system atic review and meta-analysis. JAMA . 2012;308:2507–2516. 28. Berwanger O, Nicolau JC, Carvalho AC, et al. Ticagrelor vs clopidogrel after fibrinolytic therapy in patients with ST-elevation myocardial infarction: a ran domized clinical trial. JAMA Cardiol . 2018;3:391–399.

4.3.3. Intravenous P2Y12 Inhibition

1. Bhatt DL, Lincoff AM, Gibson CM, et al. Intravenous platelet blockade with cangrelor during PCI. N Engl J Med . 2009;361:2330–2341. 2. Bhatt DL, Stone GW, Mahaffey KW, et al. Effect of platelet inhibition with cangrelor during PCI on ischemic events. N Engl J Med . 2013;368:1303– 1313. 3. Harrington RA, Stone GW, McNulty S, et al. Platelet inhibition with cangrelor in patients undergoing PCI. N Engl J Med . 2009;361:2318–2329. 4. Steg PG, Bhatt DL, Hamm CW, et al. Effect of cangrelor on periprocedural outcomes in percutaneous coronary interventions: a pooled analysis of patient-level data. Lancet . 2013;382:1981–1992. 5. Lawton JS, Tamis-Holland JE, Bangalore S, et al. 2021 ACC/AHA/SCAI guideline for coronary artery revascularization: a report of the American Col lege of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation . 2022;145:e18–e114. 6. Akers WS, Oh JJ, Oestreich JH, et al. Pharmacokinetics and pharmaco dynamics of a bolus and infusion of cangrelor: a direct, parenteral P2Y12 receptor antagonist. J Clin Pharmacol . 2010;50:27–35. 7. Angiolillo DJ, Firstenberg MS, Price MJ, et al. Bridging antiplatelet therapy with cangrelor in patients undergoing cardiac surgery: a randomized con trolled trial. JAMA . 2012;307:265–274. 8. FDA. Cangrelor prescribing information for intravenous use. Accessed October 5, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/ label/2019/204958s002lbl.pdf.

4.3.4. Intravenous Glycoprotein IIb/IIIa Inhibitors

1. Stone GW, Maehara A, Witzenbichler B, et al. Intracoronary abciximab and aspiration thrombectomy in patients with large anterior myocardial infarc tion: the INFUSE-AMI randomized trial. JAMA . 2012;307:1817–1826. 2. Thiele H, Wohrle J, Hambrecht R, et al. Intracoronary versus intravenous bo lus abciximab during primary percutaneous coronary intervention in patients with acute ST-elevation myocardial infarction: a randomised trial. Lancet . 2012;379:923–931. 3. Stone GW, Grines CL, Cox DA, et al. Comparison of angioplasty with stent ing, with or without abciximab, in acute myocardial infarction. N Engl J Med . 2002;346:957–966. 4. Giugliano RP, White JA, Bode C, et al. Early versus delayed, provisional ep tifibatide in acute coronary syndromes. N Engl J Med . 2009;360:2176– 2190. 5. Kastrati A, Neumann FJ, Schulz S, et al. Abciximab and heparin ver sus bivalirudin for non-ST-elevation myocardial infarction. N Engl J Med . 2011;365:1980–1989. 6. Lawton JS, Tamis-Holland JE, Bangalore S, et al. 2021 ACC/AHA/SCAI guideline for coronary artery revascularization: a report of the American Col lege of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation . 2022;145:e18–e114. 7. Zhao XQ, Theroux P, Snapinn SM, Sax FL. Intracoronary thrombus and platelet glycoprotein IIb/IIIa receptor blockade with tirofiban in unstable angina or non-Q-wave myocardial infarction. Angiographic results from the PRISM-PLUS trial (Platelet receptor inhibition for ischemic syndrome man agement in patients limited by unstable signs and symptoms). PRISM-PLUS Investigators. Circulation . 1999;100:1609–1615. 8. Ohlmann P, Reydel P, Jacquemin L, et al. Prehospital abciximab in ST-seg ment elevation myocardial infarction: results of the randomized, double-blind MISTRAL study. Circ Cardiovasc Interv . 2012;5:69. 9. Bertrand OF, Larose E, Bagur R, et al. A randomized double-blind placebocontrolled study comparing intracoronary versus intravenous abciximab in patients with ST-elevation myocardial infarction undergoing transradial rescue percutaneous coronary intervention after failed thrombolysis. Am J Cardiol . 2018;122:47–53. 10. Sanati HR, Zahedmehr A, Firouzi A, et al. Intracoronary versus intravenous eptifibatide during percutaneous coronary intervention for acute ST-seg ment elevation myocardial infarction; a randomized controlled trial. Cardio vasc Interv Ther . 2017;32:351–357. 11. Kastrati A, Mehilli J, Neumann FJ, et al. Abciximab in patients with acute coronary syndromes undergoing percutaneous coronary intervention af ter clopidogrel pretreatment: the ISAR-REACT 2 randomized trial. JAMA . 2006;295:1531–1538.

4.4. Parenteral Anticoagulation

1. Risk of myocardial infarction and death during treatment with low dose as pirin and intravenous heparin in men with unstable coronary artery disease. The RISC Group. Lancet . 1990;336:827–830. 2. Cohen M, Adams PC, Parry G, et al. Combination antithrombotic therapy in unstable rest angina and non-Q-wave infarction in nonprior aspirin users. Primary end points analysis from the ATACS trial. Antithrombotic Therapy in Acute Coronary Syndromes Research Group. Circulation . 1994;89:81–88. 3. Oler A, Whooley MA, Oler J, Grady D. Adding heparin to aspirin reduces the incidence of myocardial infarction and death in patients with unstable angina. A meta-analysis. JAMA . 1996;276:811–815. 4. Theroux P, Ouimet H, McCans J, et al. Aspirin, heparin, or both to treat acute unstable angina. N Engl J Med . 1988;319:1105–1111. 5. Yusuf S, Mehta SR, Chrolavicius S, et al. Fifth Organization to Assess Strategies in Acute Ischemic Syndromes Investigators. Comparison of fondaparinux and enoxaparin in acute coronary syndromes. N Engl J Med . 2006;354:1464–1476. 6. Steg PG, Jolly SS, Mehta SR, et al. Futura Oasis Trial Group. Low-dose vs standard-dose unfractionated heparin for percutaneous coronary interven tion in acute coronary syndromes treated with fondaparinux: the FUTURA/ OASIS-8 randomized trial. JAMA . 2010;304:1339–1349. 7. Murphy SA, Gibson CM, Morrow DA, et al. Efficacy and safety of the lowmolecular weight heparin enoxaparin compared with unfractionated heparin across the acute coronary syndrome spectrum: a meta-analysis. Eur Heart J . 2007;28:2077–2086. 8. Ferguson JJ, Califf RM, Antman EM, et al. Enoxaparin vs unfractionated heparin in high-risk patients with non-ST-segment elevation acute coronary syndromes managed with an intended early invasive strategy: primary re sults of the SYNERGY randomized trial. JAMA . 2004;292:45–54. 9. Antman EM, Louwerenburg HW, Baars HF, et al. Enoxaparin as adjunctive antithrombin therapy for ST-elevation myocardial infarction: results of the ENTIRE-Thrombolysis in Myocardial Infarction (TIMI) 23 Trial. Circulation . 2002;105:1642–1649. 10. Antman EM, Morrow DA, McCabe CH, et al. Enoxaparin versus unfraction ated heparin with fibrinolysis for ST-elevation myocardial infarction. N Engl J Med . 2006;354:1477–1488. 11. Cohen M, Demers C, Gurfinkel EP, et al. A comparison of low-molecularweight heparin with unfractionated heparin for unstable coronary artery disease. Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events Study Group. N Engl J Med . 1997;337:447–452. 12. Granger CB, Miller JM, Bovill EG, et al. Rebound increase in thrombin gen eration and activity after cessation of intravenous heparin in patients with acute coronary syndromes. Circulation . 1995;91:1929–1935. 13. Bahit MC, Topol EJ, Califf RM, et al. Reactivation of ischemic events in acute coronary syndromes: results from GUSTO-IIb. Gobal Use of Strategies To Open occluded arteries in acute coronary syndromes. J Am Coll Cardiol . 2001;37:1001–1007. 14. Stone GW, Witzenbichler B, Guagliumi G, et al. Bivalirudin during primary PCI in acute myocardial infarction. N Engl J Med . 2008;358:2218–2230. 15. Li Y, Liang Z, Qin L, et al. Bivalirudin plus a high-dose infusion versus hepa rin monotherapy in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: a randomised trial. Lancet . 2022;400:1847–1857. 16. Cavender MA, Sabatine MS. Bivalirudin versus heparin in patients planned for percutaneous coronary intervention: a meta-analysis of randomised con trolled trials. Lancet . 2014;384:599–606. 17. Bangalore S, Toklu B, Kotwal A, et al. Anticoagulant therapy during primary percutaneous coronary intervention for acute myocardial infarction: a metaanalysis of randomized trials in the era of stents and P2Y12 inhibitors. BMJ (Online) . 2014;349:. 18. Steg PG, van ‘t Hof A, Hamm CW, et al. Bivalirudin started during emergency transport for primary PCI. N Engl J Med . 2013;369:2207–2217. 19. Han Y, Guo J, Zheng Y, et al. Bivalirudin vs heparin with or without tirofi ban during primary percutaneous coronary intervention in acute myocardial infarction: the BRIGHT randomized clinical trial. JAMA . 2015;313:1336– 1346. 20. Stone GW, White HD, Ohman EM, et al. Bivalirudin in patients with acute coronary syndromes undergoing percutaneous coronary intervention: a subgroup analysis from the Acute Catheterization and Urgent Intervention Triage strategy (ACUITY) trial. Lancet . 2007;369:907–919. 21. Kastrati A, Neumann FJ, Schulz $S,$ et al. Abciximab and heparin ver sus bivalirudin for non-ST-elevation myocardial infarction. N Engl J Med . 2011;365:1980–1989. 22. Kheiri B, Rao SV, Osman M, et al. Meta-analysis of bivalirudin versus heparin in transradial coronary interventions. Catheter Cardiovasc Interv . 2020;96:1240–1248. 23. Bikdeli B, Erlinge D, Valgimigli M, et al. Bivalirudin versus heparin during PCI in NSTEMI: individual patient data meta-analysis of large randomized trials. Circulation . 2023;148:1207–1219. 24. Montalescot G, Zeymer U, Silvain J, et al. Intravenous enoxaparin or unfrac tionated heparin in primary percutaneous coronary intervention for ST-ele vation myocardial infarction: the international randomised open-label ATOLL trial. Lancet . 2011;378:693–703. 25. Collet JP, Huber K, Cohen M, et al. A direct comparison of intravenous enoxaparin with unfractionated heparin in primary percutaneous coronary intervention (from the ATOLL trial). Am J Cardiol . 2013;112:1367–1372. 26. Silvain J, Beygui F, Barthelemy O, et al. Efficacy and safety of enoxaparin versus unfractionated heparin during percutaneous coronary intervention: systematic review and meta-analysis. BMJ . 2012;344:e553. 27. Yusuf S, Mehta SR, Chrolavicius $S,$ et al. Effects of fondaparinux on mortal ity and reinfarction in patients with acute ST-segment elevation myocardial infarction: the OASIS-6 randomized trial. JAMA . 2006;295:1519–1530. 28. Ross AM, Molhoek P, Lundergan C, et al. Randomized comparison of enoxa parin, a low-molecular-weight heparin, with unfractionated heparin adjunc tive to recombinant tissue plasminogen activator thrombolysis and aspirin: second trial of Heparin and Aspirin Reperfusion Therapy (HART II). Circula tion . 2001;104:648–652. 29. Efficacy and safety of tenecteplase in combination with enoxaparin, abcix imab, or unfractionated heparin: the ASSENT-3 randomised trial in acute myocardial infarction. Lancet . 2001;358:605–613. 30. Peters RJ, Joyner C, Bassand JP, et al. The role of fondaparinux as an adjunct to thrombolytic therapy in acute myocardial infarction: a subgroup analysis of the OASIS-6 trial. Eur Heart J . 2008;29:324–331. 31. Lawton JS, Tamis-Holland JE, Bangalore S, et al. 2021 ACC/AHA/SCAI guideline for coronary artery revascularization: a report of the American Col lege of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation . 2022;145:e18–e114. 32. Thygesen K, Alpert JS, Jaffe AS, et al. Fourth universal definition of myocar dial infarction (2018). Circulation . 2018;138:e618–e651. 33. Zeymer U, Rao SV, Montalescot G. Anticoagulation in coronary intervention. Eur Heart J . 2016;37:3376–3385. 34. Mahaffey KW, Lewis BE, Wildermann NM, et al. The anticoagulant therapy with bivalirudin to assist in the performance of percutaneous coronary inter vention in patients with heparin-induced thrombocytopenia (ATBAT) study: main results. J Invasive Cardiol . 2003;15:611–616. 35. Lewis BE, Matthai WH Jr, Cohen M, et al. Argatroban anticoagulation during percutaneous coronary intervention in patients with heparin-induced throm bocytopenia. Catheter Cardiovasc Interv . 2002;57:177–184. 36. Eikelboom JW, Anand SS, Malmberg K, et al. Unfractionated heparin and low-molecular-weight heparin in acute coronary syndrome without ST el evation: a meta-analysis. Lancet . 2000;355:1936–1942. 37. Ducrocq G, Jolly S, Mehta SR, et al. Activated clotting time and outcomes during percutaneous coronary intervention for non-ST-segment-elevation myocardial infarction: insights from the FUTURA/OASIS-8 Trial. Circ Car diovasc Interv . 2015;8:e002044. 38. James S, Koul S, Andersson J, et al. Bivalirudin versus heparin monother apy in ST-segment-elevation myocardial infarction. Circ Cardiovasc Interv . 2021;14:e008969. 39. Wang ZD, Chen YX, Liu M, et al. Safety of bivalirudin combined with ticagrelor in the emergency PCI in patients with acute ST-segment elevation myocar dial infarction. Clin Appl Thromb Hemost . 2022;28:10760296221077973. 40. Navarese EP, Schulze V, Andreotti F, et al. Comprehensive meta-analysis of safety and efficacy of bivalirudin versus heparin with or without routine glycoprotein IIb/IIIa inhibitors in patients with acute coronary syndrome. J Am Coll Cardiol Intv . 2015;8:201–213. 41. Stone GW, McLaurin BT, Cox DA, et al. Bivalirudin for patients with acute coronary syndromes. N Engl J Med . 2006;355:2203–2216. 42. Valgimigli M, Frigoli E, Leonardi S, et al. Bivalirudin or unfractionated heparin in acute coronary syndromes. N Engl J Med . 2015;373:997–1009. 43. An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. N Engl J Med . 1993;329:673–682. 44. Giraldez RR, Nicolau JC, Corbalan R, et al. Enoxaparin is superior to un fractionated heparin in patients with ST elevation myocardial infarction un dergoing fibrinolysis regardless of the choice of lytic: an ExTRACT-TIMI 25 analysis. Eur Heart J . 2007;28:1566–1573. 45. Eikelboom JW, Quinlan DJ, Mehta SR, et al. Unfractionated and low-molec ular-weight heparin as adjuncts to thrombolysis in aspirin-treated patients with ST-elevation acute myocardial infarction: a meta-analysis of the ran domized trials. Circulation . 2005;112:3855–3867.

4.5. Lipid Management

1. Schwartz GG, Olsson AG, Ezekowitz MD, et al. Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study: a randomized controlled trial. JAMA . 2001;285:1711–1718. 2. de Lemos JA, Blazing MA, Wiviott SD, et al. Early intensive vs a delayed con servative simvastatin strategy in patients with acute coronary syndromes: phase Z of the A to Z trial. JAMA . 2004;292:1307–1316. 3. Cannon CP, Braunwald E, McCabe CH, et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med . 2004;350:1495–1504. 4. Baigent C, Blackwell L, Emberson J, et al. Efficacy and safety of more in tensive lowering of LDL cholesterol: a meta-analysis of data from 170 000 participants in 26 randomised trials. Lancet . 2010;376:1670–1681. 5. Cannon CP, Blazing MA, Giugliano RP, et al. Ezetimibe added to statin ther apy after acute coronary syndromes. N Engl J Med . 2015;372:2387–2397. 6. Schwartz GG, Steg PG, Szarek M, et al. Alirocumab and cardiovascular outcomes after acute coronary syndrome. N Engl J Med . 2018;379:2097– 2107. 7. Sabatine MS, Giugliano RP, Pedersen TR. Evolocumab in patients with car diovascular disease. N Engl J Med . 2017;377:787–788. 8. Moriarty PM, Thompson PD, Cannon CP, et al. Efficacy and safety of ali rocumab vs ezetimibe in statin-intolerant patients, with a statin rechal lenge arm: the ODYSSEY ALTERNATIVE randomized trial. J Clin Lipidol . 2015;9:758–769. 9. Nissen SE, Stroes E, Dent-Acosta RE, et al. Efficacy and tolerability of evo locumab vs ezetimibe in patients with muscle-related statin intolerance: the GAUSS-3 randomized clinical trial. JAMA . 2016;315:1580–1590. 10. Nissen SE, Lincoff AM, Brennan D, et al. Bempedoic acid and cardiovascu lar outcomes in statin-intolerant patients. N Engl J Med . 2023;388:1353– 1364. 11. Giugliano RP, Pedersen TR, Park JG, et al. Clinical efficacy and safety of achieving very low LDL-cholesterol concentrations with the PCSK9 inhibi tor evolocumab: a prespecified secondary analysis of the FOURIER trial. Lancet . 2017;390:1962–1971. 12. Schwartz GG, Gabriel Steg P, Bhatt DL, et al. Clinical efficacy and safety of alirocumab after acute coronary syndrome according to achieved level of low-density lipoprotein cholesterol: a propensity score-matched analysis of the ODYSSEY OUTCOMES trial. Circulation . 2021;143:1109–1122. 13. Wiviott SD, Cannon CP, Morrow DA, et al. Can low-density lipoprotein be too low? The safety and efficacy of achieving very low low-density lipoprotein with intensive statin therapy: a PROVE IT-TIMI 22 substudy. J Am Coll Car diol . 2005;46:1411–1416. 14. Virani SS, Newby LK, Arnold SV, et al. 2023 AHA/ACC/ACCP/ASPC/ NLA/PCNA guideline for the management of patients with chronic coro nary disease: a report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines. Circulation . 2023;148:e9–e119. 15. Ulvenstam A, Graipe A, Irewall AL, et al. Incidence and predictors of cardio vascular outcomes after acute coronary syndrome in a population-based cohort study. Sci Rep . 2023;13:3447. 16. Steen DL, Khan I, Andrade K, et al. Event rates and risk factors for recurrent cardiovascular events and mortality in a contemporary post acute coronary syndrome population representing 239234 patients during 2005 to 2018 in the United States. J Am Heart Assoc . 2022;11:e022198. 17. Baigent C, Blackwell L, Emberson J, et al. Cholesterol Treatment Trialists Collaboration. Efficacy and safety of more intensive lowering of LDL choles terol: a meta-analysis of data from 170000 participants in 26 randomised trials. Lancet . 2010;376:1670–1681. 18. Barth JH, Jackson BM, Farrin AJ, et al. Change in serum lipids after acute coronary syndromes: secondary analysis of SPACE ROCKET study data and a comparative literature review. Clin Chem . 2010;56:1592–1598. 19. Murphy SA, Cannon CP, Wiviott SD, et al. Effect of intensive lipid-lowering therapy on mortality after acute coronary syndrome (a patient-level analysis of the Aggrastat to Zocor and Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 trials). Am J Car diol . 2007;100:1047–1051. 20. Gencer B, Mach F, Murphy SA, et al. Efficacy of evolocumab on cardiovas cular outcomes in patients with recent myocardial infarction: a prespecified secondary analysis from the FOURIER trial. JAMA Cardiol . 2020;5:952– 957. 21. Chiang CE, Schwartz GG, Elbez Y, et al. Alirocumab and cardiovascular out comes in patients with previous myocardial infarction: prespecified subanal ysis from ODYSSEY OUTCOMES. Can J Cardiol . 2022;38:1542–1549. 22. Koskinas KC, Windecker S, Pedrazzini G, et al. Evolocumab for early reduc tion of LDL cholesterol levels in patients with acute coronary syndromes (EVOPACS). J Am Coll Cardiol . 2019;74:2452–2462. 23. Leucker TM, Blaha MJ, Jones SR, et al. Effect of evolocumab on atherogen ic lipoproteins during the peri- and early postinfarction period: a placebocontrolled, randomized trial. Circulation . 2020;142:419–421. 24. Nicholls SJ, Kataoka Y, Nissen SE, et al. Effect of evolocumab on coronary plaque phenotype and burden in statin-treated patients following myocar dial infarction. J Am Coll Cardiol Img . 2022;15:1308–1321. 25. Raber L, Ueki Y, Otsuka T, et al. Effect of alirocumab added to high-in tensity statin therapy on coronary atherosclerosis in patients with acute myocardial infarction: the PACMAN-AMI randomized clinical trial. JAMA . 2022;327:1771–1781. 26. Ray KK, Wright RS, Kallend D, et al. Two phase 3 trials of inclisiran in pa tients with elevated LDL cholesterol. N Engl J Med . 2020;382:1507–1519. 27. Bytyci I, Penson PE, Mikhailidis DP, et al. Prevalence of statin intolerance: a meta-analysis. Eur Heart J . 2022;43:3213–3223. 28. Cheeley MK, Saseen JJ, Agarwala A, et al. NLA scientific statement on statin intolerance: a new definition and key considerations for ASCVD risk reduction in the statin intolerant patient. J Clin Lipidol . 2022;16:361–375. 29. Ray KK, Bays HE, Catapano AL, et al. Safety and efficacy of bempedoic acid to reduce LDL cholesterol. N Engl J Med . 2019;380:1022–1032. 30. Goldberg AC, Leiter LA, Stroes ESG, et al. Effect of bempedoic acid vs pla cebo added to maximally tolerated statins on low-density lipoprotein choles terol in patients at high risk for cardiovascular disease: the CLEAR Wisdom randomized clinical trial. JAMA . 2019;322:1780–1788. 31. Ballantyne CM, Laufs U, Ray KK, et al. Bempedoic acid plus ezetimibe fixed-dose combination in patients with hypercholesterolemia and high CVD risk treated with maximally tolerated statin therapy. Eur J Prev Cardiol . 2020;27:593–603. 32. Oyama K, Giugliano RP, Blazing MA, et al. Baseline low-density lipoprotein cholesterol and clinical outcomes of combining ezetimibe with statin therapy in IMPROVE-IT. J Am Coll Cardiol . 2021;78:1499–1507. 33. O’Donoghue ML, Giugliano RP, Wiviott SD, et al. Long-term evolocumab in patients with established atherosclerotic cardiovascular disease. Circulation . 2022;146:1109–1119. 34. Giugliano RP, Cannon CP, Blazing MA, et al. Benefit of adding ezetimibe to statin therapy on cardiovascular outcomes and safety in patients with versus without diabetes mellitus: results from IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial). Circulation . 2018;137:1571– 1582. 35. Bohula EA, Morrow DA, Giugliano RP, et al. Atherothrombotic risk strati fication and ezetimibe for secondary prevention. J Am Coll Cardiol . 2017;69:911–921. 36. Oliver W, Giugliano RP. Benefit of combination ezetimibe/simvastatin among high-risk populations: lessons from the IMPROVE-IT trial. Curr Ath eroscler Rep . 2023;25:85–93. 37. Sabatine MS, De Ferrari GM, Giugliano RP, et al. Clinical benefit of evo locumab by severity and extent of coronary artery disease: analysis from FOURIER. Circulation . 2018;138:756–766. 38. Bonaca MP, Nault P, Giugliano RP, et al. Low-density lipoprotein cholesterol lowering with evolocumab and outcomes in patients with peripheral artery disease: insights from the FOURIER trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk). Circulation . 2018;137:338–350. 39. Jukema JW, Szarek M, Zijlstra LE, et al. Alirocumab in patients with polyvas cular disease and recent acute coronary syndrome: ODYSSEY OUTCOMES trial. J Am Coll Cardiol . 2019;74:1167–1176. 40. Roe MT, Li QH, Bhatt DL, et al. Risk categorization using New American College of Cardiology/American Heart Association Guidelines for choles terol management and its relation to alirocumab treatment following acute coronary syndromes. Circulation . 2019;140:1578–1589. 41. Marston NA, Oyama K, Jarolim P, et al. Combining high-sensitivity tro ponin with the American Heart Association/American College of Car diology cholesterol guidelines to guide evolocumab therapy. Circulation . 2021;144:249–251. 42. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the man

agement of blood cholesterol: a report of the American College of Cardiol ogy/American Heart Association Task Force on Clinical Practice Guidelines. Circulation . 2019;139:e1082–e1143.

4.6. Beta-Blocker Therapy

1. Chen ZM, Pan HC, Chen YP, et al. Early intravenous then oral metoprolol in 45852 patients with acute myocardial infarction: randomised placebocontrolled trial. Lancet . 2005;366:1622–1632. 2. Roberts R, Rogers WJ, Mueller HS, et al. Immediate versus deferred betablockade following thrombolytic therapy in patients with acute myocardial infarction. Results of the Thrombolysis in Myocardial Infarction (TIMI) II-B Study. Circulation . 1991;83:422–437. 3. Freemantle N, Cleland J, Young P, et al. Beta blockade after myocar dial infarction: systematic review and meta regression analysis. BMJ . 1999;318:1730–1737. 4. de Peuter OR, Lussana F, Peters RJ, et al. A systematic review of selective and non-selective beta blockers for prevention of vascular events in patients with acute coronary syndrome or heart failure. Neth J Med . 2009;67:284– 294. 5. Dahl Aarvik M, Sandven I, Dondo TB, et al. Effect of oral beta-blocker treat ment on mortality in contemporary post-myocardial infarction patients: a systematic review and meta-analysis. Eur Heart J Cardiovasc Pharmacother . 2019;5:12–20. 6. Kontos MC, Diercks DB, Ho PM, et al. Treatment and outcomes in pa tients with myocardial infarction treated with acute beta-blocker therapy: results from the American College of Cardiology’s NCDR. Am Heart J . 2011;161:864–870. 7. Yndigegn T, Lindahl B, Mars K, et al. Beta-blockers after myocardial infarc tion and preserved ejection fraction. N Engl J Med . 2024;390:1372–1381. 8. Watanabe H, Ozasa N, Morimoto T, et al. Long-term use of carvedilol in pa tients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention. PLoS One . 2018;13:e0199347. 9. Roolvink V, Ibanez B, Ottervanger JP, et al. Early intravenous beta-blockers in patients with ST-segment elevation myocardial infarction before primary percutaneous coronary intervention. J Am Coll Cardiol . 2016;67:2705– 2715. 10. Ibanez B, Macaya C, Sanchez-Brunete V, et al. Effect of early metoprolol on infarct size in ST-segment-elevation myocardial infarction patients undergo ing primary percutaneous coronary intervention: the effect of metoprolol in cardioprotection during an acute myocardial infarction (METOCARD-CNIC) trial. Circulation . 2013;128:1495–1503.

4.7. Renin-Angiotensin-Aldosterone System Inhibitors

1. Pfeffer MA, Braunwald E, Moye LA, et al. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarc tion. N Engl J Med . 1992;327:669–677. 2. Ambrosioni E, Borghi C, Magnani B. The effect of the angiotensin-con verting-enzyme inhibitor zofenopril on mortality and morbidity after anterior myocardial infarction. N Engl J Med . 1995;332:80–85. 3. Koeber L, Torp-Pedersen C, Carlsen JE, et al. A clinical trial of the angioten sin-converting-enzyme inhibitor trandolapril in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med . 1995;333:1670– 1676. 4. ACE Inhibitor Myocardial Infarction Collaborative Group. Indications for ACE inhibitors in the early treatment of acute myocardial infarction: systematic overview of individual data from 100000 patients in randomized trials. Cir culation . 1998;97:2202–2212. 5. Pfeffer MA, McMurray JJV, Velazquez EJ, et al. Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunc tion, or both. N Engl J Med . 2003;349:1893–1906. 6. The Acute Infarction Ramipril Efficacy Study Investigators. Effect of ramipril on mortality and morbidity of survivors of acute myocardial infarction with clinical evidence of heart failure. Lancet . 1993;342:821–828. 7. Pitt B, Remme W, Zannad F, et al. Eplerenone, a selective aldosterone block er, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med . 2003;348:1309–1321. 8. Yusuf S, Teo KK, Pogue J, et al. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med . 2008;358:1547–1559. 9. McMurray JJV, Packer M, Desai AS, et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med . 2014;371:993–1004. 10. Pfeffer MA, Claggett B, Lewis EF, et al. Angiotensin receptor-neprilysin inhibition in acute myocardial infarction. N Engl J Med . 2021;385:1845– 1855. 11. Montalescot G, Pitt B, Lopez de Sa E, et al. Early eplerenone treatment in pa tients with acute ST-elevation myocardial infarction without heart failure: the

randomized double-blind REMINDER study. Eur Heart J . 2014;35:2295– 2302.

5.1. Regional Systems of STEMI Care

1. Alexander T, Mullasari AS, Joseph G, et al. A system of care for patients with ST-segment elevation myocardial infarction in India: the Tamil Na du-ST-Segment Elevation Myocardial Infarction Program. JAMA Cardiol . 2017;2:498–505. 2. Dharma S, Andriantoro H, Dakota I, et al. Hospital outcomes in STEMI pa tients after the introduction of a regional STEMI network in the metropolitan area of a developing country. AsiaIntervention . 2018;4:92–97. 3. Filgueiras Filho NM, Feitosa Filho GS, Solla DJF, et al. Implementation of a regional network for ST-segment-elevation myocardial infarction (STE MI) care and 30-day mortality in a low- to middle-income city in Brazil: findings from Salvador’s STEMI registry (RESISST). J Am Heart Assoc . 2018;7:e008624. 4. Jollis JG, Al-Khalidi HR, Roettig ML, et al. Regional systems of care demon stration project: American Heart Association Mission: Lifeline STEMI Sys tems Accelerator. Circulation . 2016;134:365–374. 5. Jollis JG, Al-Khalidi HR, Roettig ML, et al. Impact of regionalization of STsegment-elevation myocardial infarction care on treatment times and out comes for emergency medical services-transported patients presenting to hospitals with percutaneous coronary intervention: Mission: Lifeline Accel erator-2. Circulation . 2018;137:376–387. 6. Puymirat E, Simon T, Cayla G, et al. Acute myocardial infarction: changes in patient characteristics, management, and 6-month outcomes over a period of 20 years in the FAST-MI program (French Registry of Acute ST-Eleva tion or Non-ST-Elevation Myocardial Infarction) 1995 to 2015. Circulation . 2017;136:1908–1919. 7. Jacobs AK, Ali MJ, Best PJ, et al. Systems of care for ST-segment-elevation myocardial infarction: a policy statement from the American Heart Associa tion. Circulation . 2021;144:e310–e327. 8. Jollis JG, Granger CB, Zegre-Hemsey JK, et al. Treatment time and in-hos pital mortality among patients with ST-segment elevation myocardial infarc tion, 2018-2021. JAMA . 2022;328:2033–2040.

5.2.1. PPCI in STEMI

1. McNamara RL, Wang Y, Herrin J, et al. Effect of door-to-balloon time on mortality in patients with ST-segment elevation myocardial infarction. J Am Coll Cardiol . 2006;47:2180–2186. 2. De Luca G, Suryapranata H, Ottervanger JP, Antman EM. Time delay to treatment and mortality in primary angioplasty for acute myocardial infarc tion: every minute of delay counts. Circulation . 2004;109:1223–1225. 3. Berger PB, Ellis SG, Holmes DR Jr, et al. Relationship between delay in performing direct coronary angioplasty and early clinical outcome in patients with acute myocardial infarction: results from the global use of strategies to open occluded arteries in Acute Coronary Syndromes (GUSTO-IIb) trial. Circulation . 1999;100:14–20. 4. Menees DS, Peterson ED, Wang Y, et al. Door-to-balloon time and mortality among patients undergoing primary PCI. N Engl J Med 2013;369:901– 909. 5. Global Use of Strategies to Open Occluded Coronary Arteries in Acute Cor onary Syndromes Angioplasty Substudy I. A clinical trial comparing primary coronary angioplasty with tissue plasminogen activator for acute myocardial infarction. N Engl J Med 1997;336:1621–1628. 6. Keeley EC, Boura JA, Grines CL. Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review of 23 randomised trials. Lancet . 2003;361:13–20. 7. Zijlstra F, Hoorntje JC, de Boer MJ, et al. Long-term benefit of primary an gioplasty as compared with thrombolytic therapy for acute myocardial in farction. N Engl J Med . 1999;341:1413–1419. 8. Scholz KH, Maier SKG, Maier LS, et al. Impact of treatment delay on mortal ity in ST-segment elevation myocardial infarction (STEMI) patients present ing with and without haemodynamic instability: results from the German pro spective, multicentre FITT-STEMI trial. Eur Heart J . 2018;39:1065–1074. 9. Hochman JS, Sleeper LA, Webb JG, et al. Early revascularization in acute myocardial infarction complicated by cardiogenic shock. SHOCK Investiga tors. Should we emergently revascularize occluded coronaries for cardio genic shock. N Engl J Med . 1999;341:625–634. 10. Axelsson TA, Mennander A, Malmberg M, et al. Is emergency and sal vage coronary artery bypass grafting justified? The Nordic emergency/ salvage coronary artery bypass grafting study. Eur J Cardiothorac Surg 2016;49:1451–1456. 11. Liakopoulos OJ, Schlachtenberger G, Wendt D, et al. Early clinical outcomes of surgical myocardial revascularization for acute coronary syndromes com plicated by cardiogenic shock: a report from the North-Rhine-Westphalia Surgical Myocardial Infarction Registry. J Am Heart Assoc . 2019;8:e012049. 12. Schomig A, Mehilli J, Antoniucci D, et al. Mechanical reperfusion in patients with acute myocardial infarction presenting more than 12 hours from symp tom onset: a randomized controlled trial. JAMA . 2005;293:2865–2872. 13. Gierlotka M, Gasior M, Wilczek K, et al. Reperfusion by primary percutane ous coronary intervention in patients with ST-segment elevation myocardial infarction within 12 to 24 hours of the onset of symptoms (from a prospec tive national observational study [PL-ACS]). Am J Cardiol . 2011;107:501– 508. 14. Ndrepepa G, Kastrati A, Mehilli J, et al. Mechanical reperfusion and longterm mortality in patients with acute myocardial infarction presenting 12 to 48 hours from onset of symptoms. JAMA . 2009;301:487–488. 15. Bouisset F, Gerbaud E, Bataille V, et al. Percutaneous myocardial revas cularization in late-presenting patients with STEMI. J Am Coll Cardiol . 2021;78:1291–1305. 16. Hochman JS, Lamas GA, Buller CE, et al. Coronary intervention for persis tent occlusion after myocardial infarction. N Engl J Med . 2006;355:2395– 2407. 17. Steg PG, Thuaire C, Himbert D, et al. DECOPI (DEsobstruction COronaire en Post-Infarctus): a randomized multi-centre trial of occluded artery an gioplasty after acute myocardial infarction. Eur Heart J . 2004;25:2187– 2194. 18. Lawton JS, Tamis-Holland JE, Bangalore S, et al. 2021 ACC/AHA/SCAI guideline for coronary artery revascularization: a report of the American Col lege of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation . 2022;145:e18–e114. 19. Shen YC, Krumholz H, Hsia RY. Association of cardiac care regionaliza tion with access, treatment, and mortality among patients with ST-seg ment elevation myocardial infarction. Circ Cardiovasc Qual Outcomes . 2021;14:e007195. 20. Jollis JG, Al-Khalidi HR, Roettig ML, et al. Impact of regionalization of STsegment-elevation myocardial infarction care on treatment times and out comes for emergency medical services-transported patients presenting to hospitals with percutaneous coronary intervention: Mission: Lifeline Accel erator-2. Circulation . 2018;137:376–387. 21. Jollis JG, Al-Khalidi HR, Roettig ML, et al. Impact of regionalization of ST-segment-elevation myocardial infarction care on treatment times and outcomes for emergency medical services: transported patients present ing to hospitals with percutaneous coronary intervention. Circulation . 2018;137:376–387. 22. Krumholz H, Herrin, J, Miller LW, et al. Improvements in door-to-balloon time in the United States, 2005 to 2010. Circulation . 2011;124:1038–1045. 23. Yeh RW, Sidney S, Chandra M, et al. Population trends in the incidence and outcomes of acute myocardial infarction. N Engl J Med . 2010;362:2155– 2165. 24. Jhand A, Atti V, Gwon Y, et al. Meta-analysis of transradial vs transfemoral access for percutaneous coronary intervention in patients with ST elevation myocardial infarction. Am J Cardiol . 2021;141:23–30. 25. Volz S, Angeras O, Koul S, et al. Radial versus femoral access in patients with acute coronary syndrome undergoing invasive management: a pre specified subgroup analysis from VALIDATE-SWEDEHEART. Eur Heart J Acute Cardiovasc Care . 2019;8:510–519. 26. Hochman JS, Sleeper LA, White HD, et al. One-year survival following early revascularization for cardiogenic shock. JAMA . 2001;285:190–192. 27. Hochman JS, Sleeper LA, Webb JG, et al. Early revascularization and longterm survival in cardiogenic shock complicating acute myocardial infarction. JAMA . 2006;295:2511–2515. 28. Smilowitz NR, Alviar CL, Katz SD, Hochman JS. Coronary artery bypass grafting versus percutaneous coronary intervention for myocardial infarction complicated by cardiogenic shock. Am Heart J . 2020;226:255–263. 29. Hochman JS, Reynolds HR, Dzavik V, et al. Long-term effects of percutane ous coronary intervention of the totally occluded infarct-related artery in the subacute phase after myocardial infarction. Circulation . 2011;124:2320– 2328.

5.2.2. Urgent CABG Surgery

1. Pi Y, Roe MT, Holmes DN, et al. Utilization, characteristics, and in-hospital outcomes of coronary artery bypass grafting in patients with ST-segmentelevation myocardial infarction: results from the National Cardiovascular Data Registry Acute Coronary Treatment and Intervention Outcomes Net work Registry-Get With The Guidelines. Circ Cardiovasc Qual Outcomes . 2017;10:e003490. 2. Grothusen C, Friedrich C, Loehr J, et al. Outcome of stable patients with acute myocardial infarction and coronary artery bypass surgery within 48 hours: a single-center, retrospective experience. J Am Heart Assoc . 2017;6:e005498. 3. Lawton JS, Tamis-Holland JE, Bangalore S, et al. 2021 ACC/AHA/SCAI guideline for coronary artery revascularization: a report of the American Col lege of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation . 2022;145:e18–e114. 4. Patlolla SH, Kanwar A, Cheungpasitporn W, et al. Temporal trends, clinical characteristics, and outcomes of emergent coronary artery bypass graft ing for acute myocardial infarction in the United States. J Am Heart Assoc . 2021;10:e020517. 5. Thielmann M, Wendt D, Slottosch I, et al. Coronary artery bypass graft sur gery in patients with acute coronary syndromes after primary percutaneous coronary intervention: a current report from the North-Rhine Westphalia Sur gical Myocardial Infarction Registry. J Am Heart Assoc . 2021;10:e021182.

5.3. Reperfusion at Non–PCI-Capable Hospitals

1. Nielsen PH, Terkelsen CJ, Nielsen TT, et al. System delay and timing of in tervention in acute myocardial infarction (from the Danish Acute Myocardial Infarction-2 [DANAMI-2] trial). Am J Cardiol . 2011;108:776–781. 2. Dalby M, Bouzamondo A, Lechat P, Montalescot G. Transfer for primary an gioplasty versus immediate thrombolysis in acute myocardial infarction: a meta-analysis. Circulation . 2003;108:1809–1814. 3. French WJ, Gunderson M, Travis D, et al. Emergency interhospital transfer of patients with ST-segment-elevation myocardial infarction: call 9-1-1-the American Heart Association Mission: Lifeline Program. J Am Heart Assoc . 2022;11:e026700. 4. Li K, Zhang B, Zheng B, et al. Reperfusion strategy of ST-elevation myocar dial infarction: a meta-analysis of primary percutaneous coronary interven tion and pharmaco-invasive therapy. Front Cardiovasc Med . 2022;9:813325. 5. Fazel R, Joseph TI, Sankardas MA, et al. Comparison of reperfusion strate gies for ST-segment-elevation myocardial infarction: a multivariate network meta-analysis. J Am Heart Assoc . 2020;9:e015186. 6. Siontis KC, Barsness GW, Lennon RJ, et al. Pharmacoinvasive and pri mary percutaneous coronary intervention strategies in ST-elevation myo cardial infarction (from the Mayo Clinic STEMI Network). Am J Cardiol . 2016;117:1904–1910. 7. Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17187 cases of suspected acute myocardial infarction: ISIS-2. ISIS-2 (Second International Study of Infarct Survival) Collaborative Group. Lancet . 1988;2:349–360. 8. Effectiveness of intravenous thrombolytic treatment in acute myocardial infarction. Gruppo Italiano per lo Studio della Streptochinasi nell’Infarto Mio cardico (GISSI). Lancet . 1986;1:397–402. 9. An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. N Engl J Med . 1993;329:673–682. 10. Armstrong PW, Gershlick AH, Goldstein P, et al. Fibrinolysis or primary PCI in ST-segment elevation myocardial infarction. N Engl J Med . 2013;368:1379– 1387. 11. Schomig A, Mehilli J, Antoniucci D, et al. Mechanical reperfusion in patients with acute myocardial infarction presenting more than 12 hours from symp tom onset: a randomized controlled trial. JAMA . 2005;293:2865–2872. 12. Gierlotka M, Gasior M, Wilczek K, et al. Reperfusion by primary percutane ous coronary intervention in patients with ST-segment elevation myocardial infarction within 12 to 24 hours of the onset of symptoms (from a prospec tive national observational study [PL-ACS]). Am J Cardiol . 2011;107:501– 508. 13. Indications for fibrinolytic therapy in suspected acute myocardial infarction: collaborative overview of early mortality and major morbidity results from all randomised trials of more than 1000 patients. Fibrinolytic Therapy Trialists’ (FTT) Collaborative Group. Lancet . 1994;343:311–322. 14. Huber K, Goldstein P, Danchin N, et al. Enhancing the efficacy of deliv ering reperfusion therapy: a European and North American experience with ST-segment elevation myocardial infarction networks. Am Heart J . 2013;165:123–132. 15. Hsia RY, Shen YC. Percutaneous coronary intervention in the United States: risk factors for untimely access. Health Serv Res . 2016;51:592–609. 16. Nallamothu BK, Bates ER, Wang Y, et al. Driving times and distances to hospitals with percutaneous coronary intervention in the United States: implications for prehospital triage of patients with ST-elevation myocardial infarction. Circulation . 2006;113:1189–1195. 17. Horwitz JR, Nichols A, Nallamothu BK, et al. Expansion of invasive cardiac services in the United States. Circulation . 2013;128:803–810. 18. Andersen HR, Nielsen TT, Rasmussen K, et al. A comparison of coronary angioplasty with fibrinolytic therapy in acute myocardial infarction. N Engl J Med . 2003;349:733–742. 19. Pinto DS, Frederick PD, Chakrabarti AK, et al. Benefit of transferring STsegment-elevation myocardial infarction patients for percutaneous coronary intervention compared with administration of onsite fibrinolytic declines as delays increase. Circulation . 2011;124:2512–2521. 20. Yamaguchi J, Matoba T, Kikuchi M, et al. Effects of door-in to door-out time on mortality among ST-segment elevation myocardial infarction patients transferred for primary percutaneous coronary intervention - systematic re view and meta-analysis. Circ Rep . 2022;4:109–115. 21. Ward MJ, Vogus TJ, Bonnet K, et al. Breaking down walls: a qualitative evalu ation of perceived emergency department delays for patients transferred with ST-elevation myocardial infarction. BMC Emerg Med . 2020;20:60. 22. Sinnaeve PR, Armstrong PW, Gershlick AH, et al. ST-segment-elevation myocardial infarction patients randomized to a pharmaco-invasive strategy or primary percutaneous coronary intervention: Strategic Reperfusion Early After Myocardial Infarction (STREAM) 1-year mortality follow-up. Circulation . 2014;130:1139–1145.

5.3.1. Timing and Choice of Agent for Fibrinolytic Therapy

1. Halvorsen S, Huber K. Fibrinolytic treatment of ST-elevation myocardial in farction. Update 2014. Hamostaseologie . 2014;34:47–53. 2. Koutsoukis A, Kanakakis I. Challenges and unanswered questions in STEMI management. Hellenic J Cardiol . 2019;60:211–215. 3. Gershlick AH, Westerhout CM, Armstrong PW, et al. Impact of a phar macoinvasive strategy when delays to primary PCI are prolonged. Heart . 2015;101:692–698. 4. Siddiqi TJ, Usman MS, Khan MS, et al. Meta-analysis comparing primary percutaneous coronary intervention versus pharmacoinvasive therapy in transfer patients with ST-elevation myocardial infarction. Am J Cardiol . 2018;122:542–547. 5. Fazel R, Joseph TI, Sankardas MA, et al. Comparison of reperfusion strate gies for ST-segment-elevation myocardial infarction: a multivariate network meta-analysis. J Am Heart Assoc . 2020;9:e015186. 6. Bainey KR, Armstrong PW, Zheng Y, et al. Pharmacoinvasive strategy versus primary percutaneous coronary intervention in ST-elevation myocardial in farction in clinical practice: insights from the Vital Heart Response Registry. Circ Cardiovasc Interv . 2019;12:e008059. 7. Sinnaeve PR, Armstrong PW, Gershlick AH, et al. ST-segment-elevation myocardial infarction patients randomized to a pharmaco-invasive strategy or primary percutaneous coronary intervention: Strategic Reperfusion Early After Myocardial Infarction (STREAM) 1-year mortality follow-up. Circulation . 2014;130:1139–1145. 8. Indications for fibrinolytic therapy in suspected acute myocardial infarction: collaborative overview of early mortality and major morbidity results from all randomised trials of more than 1000 patients. Fibrinolytic Therapy Trialists’ (FTT) Collaborative Group. Lancet . 1994;343:311–322. 9. Late Assessment of Thrombolytic Efficacy (LATE) study with alteplase 6-24 hours after onset of acute myocardial infarction. Lancet . 1993;342:759– 766. 10. Langer A, Goodman SG, Topol EJ, et al. Late assessment of thrombolytic efficacy (LATE) study: prognosis in patients with non-Q wave myocardial infarction. (LATE Study Investigators). J Am Coll Cardiol . 1996;27:1327– 1332. 11. Bode C, Smalling RW, Berg G, et al. Randomized comparison of coronary thrombolysis achieved with double-bolus reteplase (recombinant plasmino gen activator) and front-loaded, accelerated alteplase (recombinant tissue plasminogen activator) in patients with acute myocardial infarction. The RAPID II Investigators. Circulation . 1996;94:891–898. 12. Armstrong PW, Collen D. Fibrinolysis for acute myocardial infarction: current status and new horizons for pharmacological reperfusion, part 1. Circulation . 2001;103:2862–2866. 13. Neuhaus KL, von Essen R, Tebbe U, et al. Improved thrombolysis in acute myocardial infarction with front-loaded administration of alteplase: results of the rt-PA-APSAC patency study (TAPS). J Am Coll Cardiol . 1992;19:885– 891. 14. Cannon CP, McCabe CH, Gibson CM, et al. TNK-tissue plasminogen activator in acute myocardial infarction. Results of the Thromboly sis in Myocardial Infarction (TIMI) 10A dose-ranging trial. Circulation . 1997;95:351–356. 15. Jinatongthai P, Kongwatcharapong J, Foo CY, et al. Comparative efficacy and safety of reperfusion therapy with fibrinolytic agents in patients with STsegment elevation myocardial infarction: a systematic review and network meta-analysis. Lancet . 2017;390:747–759. 16. Gunlu S, Demir M. Comparison of tenecteplase versus alteplase in STEMI patients treated with ticagrelor: a cross-sectional study. Am J Emerg Med . 2022;58:52–56. 17. Van De Werf F, Adgey J, Ardissino D, et al. Assessment of the Safety Ef ficacy of a New Thrombolytic Investigators. Single-bolus tenecteplase com pared with front-loaded alteplase in acute myocardial infarction: the AS SENT-2 double-blind randomised trial. Lancet . 1999;354:716–722. 18. Global Use of Strategies to Open Occluded Coronary Arteries I. A compari son of reteplase with alteplase for acute myocardial infarction. N Engl J Med . 1997;337:1118–1123.

5.3.2. Coronary Angiography and PCI After Fibrinolytic Therapy

1. Scheller B, Hennen B, Hammer B, et al. Beneficial effects of immediate stenting after thrombolysis in acute myocardial infarction. J Am Coll Cardiol . 2003;42:634–641. 2. Le May MR, Wells GA, Labinaz M, et al. Combined angioplasty and pharma cological intervention versus thrombolysis alone in acute myocardial infarc tion (CAPITAL AMI study). J Am Coll Cardiol . 2005;46:417–424. 3. Di Mario C, Dudek D, Piscione F, et al. Immediate angioplasty versus stan dard therapy with rescue angioplasty after thrombolysis in the Combined Abciximab REteplase Stent Study in Acute Myocardial Infarction (CA RESS-in-AMI): an open, prospective, randomised, multicentre trial. Lancet . 2008;371:559–568. 4. Cantor WJ, Fitchett D, Borgundvaag B, et al. Routine early angioplasty after fibrinolysis for acute myocardial infarction. N Engl J Med . 2009;360:2705– 2718. 5. Bohmer E, Hoffmann P, Abdelnoor M, et al. Efficacy and safety of immedi ate angioplasty versus ischemia-guided management after thrombolysis in acute myocardial infarction in areas with very long transfer distances results of the NORDISTEMI (NORwegian study on DIstrict treatment of ST-eleva tion myocardial infarction). J Am Coll Cardiol . 2010;55:102–110. 6. Gershlick AH, Stephens-Lloyd A, Hughes S, et al. Rescue angioplasty after failed thrombolytic therapy for acute myocardial infarction. N Engl J Med . 2005;353:2758–2768. 7. Sutton AG, Campbell PG, Graham R, et al. A randomized trial of rescue angioplasty versus a conservative approach for failed fibrinolysis in ST-seg ment elevation myocardial infarction: the Middlesbrough Early Revascular ization to Limit INfarction (MERLIN) trial. J Am Coll Cardiol . 2004;44:287– 296. 8. Wijeysundera HC, Vijayaraghavan R, Nallamothu BK, et al. Rescue angio plasty or repeat fibrinolysis after failed fibrinolytic therapy for ST-segment myocardial infarction. A meta-analysis of randomized trials. J Am Coll Car diol . 2007;49:422–430. 9. Collet JP, Montalescot G, Le May M, et al. Percutaneous coronary interven tion after fibrinolysis: a multiple meta-analyses approach according to the type of strategy. J Am Coll Cardiol . 2006;48:1326–1335. 10. Borgia F, Goodman SG, Halvorsen S, et al. Early routine percutaneous coro nary intervention after fibrinolysis vs. standard therapy in ST-segment el evation myocardial infarction: a meta-analysis. Eur Heart J . 2010;31:2156– 2169. 11. Fernandez-Aviles F, Alonso JJ, Castro-Beiras A, et al. Routine invasive strat egy within 24 hours of thrombolysis versus ischaemia-guided conservative approach for acute myocardial infarction with ST-segment elevation (GRA CIA-1): a randomised controlled trial. Lancet . 2004;364:1045–1053. 12. Lawton JS, Tamis-Holland JE, Bangalore $\mathsf{S},$ et al. 2021 ACC/AHA/SCAI guideline for coronary artery revascularization: a report of the American Col lege of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation . 2022;145:e18–e114. 13. de Lemos JA, Braunwald E. ST segment resolution as a tool for assessing the efficacy of reperfusion therapy. J Am Coll Cardiol . 2001;38:1283–1294. 14. Sutton AG, Campbell PG, Price DJ, et al. Failure of thrombolysis by strep tokinase: detection with a simple electrocardiographic method. Heart . 2000;84:149–156. 15. Mason PJ, Shah B, Tamis-Holland JE, et al. An update on radial artery ac cess and best practices for transradial coronary angiography and interven tion in acute coronary syndrome: a scientific statement from the American Heart Association. Circ Cardiovasc Interv . 2018;11:e000035. 16. Van de Werf F, Ristic AD, Averkov OV, et al. STREAM-2: half-dose te necteplase or primary percutaneous coronary intervention in older patients with ST-segment-elevation myocardial infarction: a randomized, open-label trial. Circulation . 2023;148:753–764. 17. Abdel-Qadir H, Yan AT, Tan M, et al. Consistency of benefit from an ear ly invasive strategy after fibrinolysis: a patient-level meta-analysis. Heart . 2015;101:1554–1561. 18. Fazel R, Joseph TI, Sankardas MA, et al. Comparison of reperfusion strate gies for ST-segment-elevation myocardial infarction: a multivariate network meta-analysis. J Am Heart Assoc . 2020;9:e015186. 19. Bainey KR, Armstrong PW, Zheng Y, et al. Pharmacoinvasive strategy versus primary percutaneous coronary intervention in ST-elevation myocardial in farction in clinical practice: insights from the Vital Heart Response Registry. Circ Cardiovasc Interv . 2019;12:e008059. 20. Madan M, Halvorsen S, Di Mario C, et al. Relationship between time to in vasive assessment and clinical outcomes of patients undergoing an early invasive strategy after fibrinolysis for ST-segment elevation myocardial in farction: a patient-level analysis of the randomized early routine invasive clinical trials. J Am Coll Cardiol Intv . 2015;8:166–174. 21. Ellis SG, Tendera M, de Belder MA, et al. Facilitated PCI in patients with ST-elevation myocardial infarction. N Engl J Med . 2008;358:2205– 2217.

6.1. Rationale and Timing for a Routine Invasive or Selec tive Invasive Approach

1. Cannon CP, Weintraub WS, Demopoulos LA, et al. Comparison of early in vasive and conservative strategies in patients with unstable coronary syn dromes treated with the glycoprotein IIb/IIIa inhibitor tirofiban. N Engl J Med . 2001;344:1879–1887. 2. Fox KA, Poole-Wilson PA, Henderson RA, et al. Interventional versus con servative treatment for patients with unstable angina or non-ST-elevation myocardial infarction: the British Heart Foundation RITA 3 randomised trial. Randomized Intervention Trial of unstable Angina. Lancet . 2002;360:743– 751. 3. Invasive compared with non-invasive treatment in unstable coronary-artery disease: FRISC II prospective randomised multicentre study. Fragmin and Fast Revascularisation during Instability in Coronary artery disease Investi gators. Lancet . 1999;354:708–715. 4. O’Donoghue M, Boden WE, Braunwald E, et al. Early invasive vs conser vative treatment strategies in women and men with unstable angina and non-ST-segment elevation myocardial infarction: a meta-analysis. JAMA . 2008;300:71–80. 5. Mehta SR, Cannon CP, Fox KA, et al. Routine vs selective invasive strategies in patients with acute coronary syndromes: a collaborative meta-analysis of randomized trials. JAMA . 2005;293:2908–2917. 6. Fox KA, Clayton TC, Damman P, et al. Long-term outcome of a routine ver sus selective invasive strategy in patients with non-ST-segment elevation acute coronary syndrome a meta-analysis of individual patient data. J Am Coll Cardiol . 2010;55:2435–2445. 7. de Winter RJ, Windhausen F, Cornel JH, et al. Early invasive versus selec tively invasive management for acute coronary syndromes. N Engl J Med . 2005;353:1095–1104. 8. Jobs A, Mehta SR, Montalescot G, et al. Optimal timing of an invasive strat egy in patients with non-ST-elevation acute coronary syndrome: a metaanalysis of randomised trials. Lancet . 2017;390:737–746. 9. Yoshida R, Ishii H, Morishima I, et al. Early versus delayed invasive strategy in patients with non-ST-elevation acute coronary syndrome and concomitant congestive heart failure. J Cardiol . 2019;74:320–327. 10. Zoni CR, Mukherjee D, Gulati M. Proposed new classification for acute coro nary syndrome: acute coronary syndrome requiring immediate reperfusion. Catheter Cardiovasc Interv . 2023;101:1177–1181. 11. Mehta SR, Granger CB, Boden WE, et al. Early versus delayed invasive in tervention in acute coronary syndromes. N Engl J Med . 2009;360:2165– 2175. 12. Kofoed KF, Kelbaek H, Hansen PR, et al. Early versus standard care inva sive examination and treatment of patients with non-ST-segment elevation acute coronary syndrome verdict randomized controlled trial. Circulation . 2018;138:2741–2750. 13. Scanlon PJ, Faxon DP, Audet AM, et al. ACC/AHA guidelines for coronary angiography. A report of the American College of Cardiology/American Heart Association Task orce on practice guidelines (Committee on Coronary Angiography). Circulation . 1999;99:2345–2357. 14. Elgendy IY, Mahmoud AN, Wen X, Bavry AA. Meta-analysis of randomized trials of long-term all-cause mortality in patients with non-ST-elevation acute coronary syndrome managed with routine invasive versus selective invasive strategies. Am J Cardiol . 2017;119:560–564. 15. Awan A, Ogunti R, Fatima U, et al. Timing of percutaneous coronary inter vention in non-ST elevation acute coronary syndrome: meta-analysis and systematic review of literature. Cardiovasc Revasc Med . 2020;21:1398– 1404. 16. Kite TA, Kurmani SA, Bountziouka V, et al. Timing of invasive strategy in non-ST-elevation acute coronary syndrome: a meta-analysis of randomized controlled trials. Eur Heart J . 2022;43:3148–3161. 17. Tamis-Holland JE, Jneid H, Reynolds HR, et al. Contemporary diagnosis and management of patients with myocardial infarction in the absence of ob

structive coronary artery disease: a scientific statement from the American Heart Association. Circulation . 2019;139:e891–e908. 18. Lawton JS, Tamis-Holland JE, Bangalore S, et al. 2021 ACC/AHA/SCAI guideline for coronary artery revascularization: a report of the American Col lege of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation . 2022;145:e18–e114.

7.1. Vascular Access Approach for PCI

1. Valgimigli M, Frigoli E, Leonardi S, et al. Radial versus femoral access and bi valirudin versus unfractionated heparin in invasively managed patients with acute coronary syndrome (MATRIX): final 1-year results of a multicentre, randomised controlled trial. Lancet . 2018;392:835–848. 2. Bernat I, Horak D, Stasek J, et al. ST-segment elevation myocardial infarc tion treated by radial or femoral approach in a multicenter randomized clini cal trial: the STEMI-RADIAL trial. J Am Coll Cardiol . 2014;63:964–972. 3. Gargiulo G, Giacoppo D, Jolly SS, et al. Effects on mortality and major bleeding of radial versus femoral artery access for coronary angiography or percutaneous coronary intervention: meta-analysis of individual patient data from 7 multicenter randomized clinical trials. Circulation . 2022;146:1329– 1343. 4. Ando G, Capodanno D. Radial versus femoral access in invasively managed patients with acute coronary syndrome: a systematic review and meta-anal ysis. Ann Intern Med . 2015;163:932–940. 5. Ando G, Capodanno D. Radial access reduces mortality in patients with acute coronary syndromes: results from an updated trial sequential analysis of randomized trials. J Am Coll Cardiol Intv . 2016;9:660–670. 6. Valgimigli M, Gagnor A, Calabro P, et al. Radial versus femoral access in patients with acute coronary syndromes undergoing invasive management: a randomised multicentre trial. Lancet . 2015;385:2465–2476. 7. Lawton JS, Tamis-Holland JE, Bangalore S, et al. 2021 ACC/AHA/SCAI guideline for coronary artery revascularization: a report of the American Col lege of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation . 2022;145:e18–e114. 8. Masoudi FA, Ponirakis A, de Lemos JA, et al. Trends in US cardiovascular care: 2016 report from 4 ACC national cardiovascular data registries. J Am Coll Cardiol . 2017;69:1427–1450. 9. Kok MM, Weernink MGM, von Birgelen C, et al. Patient preference for radial versus femoral vascular access for elective coronary procedures: the PRE VAS study. Catheter Cardiovasc Interv . 2018;91:17–24. 10. Gaudino M, Benedetto U, Fremes S, et al. Association of radial artery graft vs saphenous vein graft with long-term cardiovascular outcomes among pa tients undergoing coronary artery bypass grafting: a systematic review and meta-analysis. JAMA 2020;324:179–187. 11. Dahal K, Rijal J, Lee J, et al. Transulnar versus transradial access for coro nary angiography or percutaneous coronary intervention: a meta-analysis of randomized controlled trials. Catheter Cardiovasc Interv . 2016;87:857–865. 12. Talha KM, Waqar E, Ashley KE, et al. Distal trans-radial access compared to conventional trans-radial access in coronary interventions: a meta-analysis. Crit Pathw Cardiol . 2022;21:176–178. 13. Jolly SS, AlRashidi S, d’Entremont MA, et al. Routine ultrasonography guid ance for femoral vascular access for cardiac procedures: the UNIVERSAL randomized clinical trial. JAMA Cardiol . 2022;7:1110–1118. 14. Ferrante G, Rao SV, Juni P, et al. Radial versus femoral access for coro nary interventions across the entire spectrum of patients with coronary ar tery disease: a meta-analysis of randomized trials. J Am Coll Cardiol Intv . 2016;9:1419–1434. 15. Le May M, Wells G, So D, et al. Safety and efficacy of femoral access vs radial access in ST-segment elevation myocardial infarction: the SAFARISTEMI randomized clinical trial. JAMA Cardiol . 2020;5:126–134.

7.2. Use of Aspiration Thrombectomy

1. Frobert O, Lagerqvist B, Olivecrona GK, et al. Thrombus aspiration during STsegment elevation myocardial infarction. N Engl J Med . 2013;369:1587– 1597. 2. Jolly SS, Cairns JA, Yusuf $S,$ et al. Randomized trial of primary PCI with or without routine manual thrombectomy. N Engl J Med . 2015;372:1389– 1398. 3. Jolly SS, James S, Dzavik V, et al. Thrombus aspiration in ST-segment-ele vation myocardial infarction: an individual patient meta-analysis: Thrombec tomy Trialists Collaboration. Circulation . 2017;135:143–152. 4. Stone GW, Maehara A, Witzenbichler B, et al. Intracoronary abciximab and aspiration thrombectomy in patients with large anterior myocardial infarc tion: the INFUSE-AMI randomized trial. JAMA . 2012;307:1817–1826. 5. Lawton JS, Tamis-Holland JE, Bangalore S, et al. 2021 ACC/AHA/SCAI guideline for coronary artery revascularization: a report of the American Col lege of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation . 2022;145:e18–e114. 6. Henriques JP, Zijlstra F, Ottervanger JP, et al. Incidence and clinical signifi cance of distal embolization during primary angioplasty for acute myocardial infarction. Eur Heart J . 2002;23:1112–1117. 7. Stone GW, Peterson MA, Lansky AJ, et al. Impact of normalized myocardial perfusion after successful angioplasty in acute myocardial infarction. J Am Coll Cardiol . 2002;39:591–597. 8. Dudek D, Mielecki W, Burzotta F, et al. Thrombus aspiration followed by direct stenting: a novel strategy of primary percutaneous coronary interven tion in ST-segment elevation myocardial infarction. Results of the PolishItalian-Hungarian RAndomized ThrombEctomy Trial (PIHRATE Trial). Am Heart J . 2010;160:966–972. 9. Sardella G, Mancone M, Bucciarelli-Ducci C, et al. Thrombus aspiration during primary percutaneous coronary intervention improves myocardial reperfusion and reduces infarct size: the EXPIRA (thrombectomy with ex port catheter in infarct-related artery during primary percutaneous coronary intervention) prospective, randomized trial. J Am Coll Cardiol . 2009;53:309– 315. 10. Svilaas T, Vlaar PJ, van der Horst IC, et al. Thrombus aspiration dur ing primary percutaneous coronary intervention. N Engl J Med . 2008;358:557–567. 11. Vlaar PJ, Svilaas T, van der Horst IC, et al. Cardiac death and reinfarction after 1 year in the Thrombus Aspiration during Percutaneous coronary in tervention in Acute myocardial infarction Study (TAPAS): a 1-year follow-up study. Lancet . 2008;371:1915–1920. 12. Jolly SS, Cairns JA, Yusuf S, et al. Outcomes after thrombus aspiration for ST elevation myocardial infarction: 1-year follow-up of the prospective ran domised TOTAL trial. Lancet (London, England) . 2016;387:127–135. 13. Lagerqvist B, Frobert O, Olivecrona GK, et al. Outcomes 1 year after throm bus aspiration for myocardial infarction. N Engl J Med . 2014;371:1111– 1120.

7.3. Use of Intracoronary Imaging

1. Lee JM, Choi KH, Song YB, et al. Intravascular imaging-guided or angiogra phy-guided complex PCI. N Engl J Med . 2023;388:1668–1679. 2. Ali ZA, Landmesser U, Maehara A, et al. Optical coherence tomographyguided versus angiography-guided PCI. N Engl J Med . 2023;389:1466– 1476. 3. Hong SJ, Mintz GS, Ahn CM, et al. Effect of intravascular ultrasound-guided drug-eluting stent implantation: 5-year follow-up of the IVUS-XPL random ized trial. J Am Coll Cardiol Intv . 2020;13:62–71. 4. Holm NR, Andreasen LN, Neghabat O, et al. OCT or angiogra phy guidance for PCI in complex bifurcation lesions. N Engl J Med . 2023;389:1477–1487. 5. Gao XF, Ge Z, Kong XQ, et al. 3-year outcomes of the ULTIMATE trial com paring intravascular ultrasound versus angiography-guided drug-eluting stent implantation. J Am Coll Cardiol Intv . 2021;14:247–257. 6. Kang DY, Ahn JM, Yun SC, et al. Guiding intervention for complex coronary lesions by optical coherence tomography or intravascular ultrasound. J Am Coll Cardiol . 2024;83:401–413. 7. Ali ZA, Maehara A, Genereux P, et al. Optical coherence tomography com pared with intravascular ultrasound and with angiography to guide coronary stent implantation (ILUMIEN III: OPTIMIZE PCI): a randomised controlled trial. Lancet . 2016;388:2618–2628. 8. Kubo T, Shinke T, Okamura T, et al. Optical frequency domain imaging vs. in travascular ultrasound in percutaneous coronary intervention (OPINION tri al): one-year angiographic and clinical results. Eur Heart J . 2017;38:3139– 3147. 9. Chamie D, Costa JR Jr, Damiani LP, et al. Optical coherence tomography versus intravascular ultrasound and angiography to guide percutaneous coronary interventions: the iSIGHT randomized trial. Circ Cardiovasc Interv . 2021;14:e009452. 10. Muramatsu T, Ozaki Y, Nanasato M, et al. Comparison between optical frequency domain imaging and intravascular ultrasound for percutane ous coronary intervention guidance in biolimus A9-eluting stent implan tation: a randomized MISTIC-1 non-inferiority trial. Circ Cardiovasc Interv . 2020;13:e009314. 11. Stone GW, Christiansen EH, Ali ZA, et al. Intravascular imaging-guided cor onary drug-eluting stent implantation: an updated network meta-analysis. Lancet . 2024;403:824–837. 12. Lawton JS, Tamis-Holland JE, Bangalore S, et al. 2021 ACC/AHA/SCAI guideline for coronary artery revascularization: a report of the American Col lege of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation . 2022;145:e18–e114. 13. Ladwiniec A, Walsh SJ, Holm NR, et al. Intravascular ultrasound to guide left main stem intervention: a NOBLE trial substudy. EuroIntervention . 2020;16:201–209. 14. Maehara A, Matsumura M, Ali ZA, et al. IVUS-guided versus OCT-guided coronary stent implantation: a critical appraisal. J Am Coll Cardiol Intv . 2017;10:1487–1503. 15. Truesdell AG, Alasnag MA, Kaul P, et al. Intravascular imaging during per cutaneous coronary intervention: JACC state-of-the-art review. J Am Coll Cardiol . 2023;81:590–605. 16. Prati F, Romagnoli E, Burzotta F, et al. Clinical impact of OCT findings during PCI: the CLI-OPCI II study. J Am Coll Cardiol Img . 2015;8:1297–1305. 17. Soeda T, Uemura S, Park SJ, et al. Incidence and clinical significance of poststent optical coherence tomography findings: one-year follow-up study from a multicenter registry. Circulation . 2015;132:1020–1029. 18. Giacoppo D, Laudani C, Occhipinti G, et al. Coronary angiography, intra vascular ultrasound, and optical coherence tomography for guiding of per cutaneous coronary intervention: a systematic review and network metaanalysis. Circulation . 2024;149:1065–1086.

7.4.1. Management of Multivessel CAD in STEMI

1. Mehta SR, Wood DA, Storey RF, et al. Complete revascularization with multi vessel PCI for myocardial infarction. N Engl J Med . 2019;381:1411–1421. 2. Gershlick AH, Khan JN, Kelly DJ, et al. Randomized trial of complete versus lesion-only revascularization in patients undergoing primary percutaneous coronary intervention for STEMI and multivessel disease: the CvLPRIT trial. J Am Coll Cardiol . 2015;65:963–972. 3. Bainey KR, Engstroem T, Smits PC, et al. Complete vs culprit-lesion-only re vascularization for ST-segment elevation myocardial infarction: a systematic review and meta-analysis. JAMA Cardiol . 2020;5:881–888. 4. Engstrom T, Kelbaek H, Helqvist S, et al. Complete revascularisation versus treatment of the culprit lesion only in patients with ST-segment elevation myocardial infarction and multivessel disease (DANAMI-3-PRIMULTI): an open-label, randomised controlled trial. Lancet . 2015;386:665–671. 5. Di Mario C, Mara S, Flavio A, et al. Single vs multivessel treatment during primary angioplasty: results of the multicentre randomised HEpacoat for cuLPrit or multivessel stenting for Acute Myocardial Infarction (HELP AMI) Study. Int J Cardiovasc Intervent . 2004;6:128–133. 6. Politi L, Sgura F, Rossi R, et al. A randomised trial of target-vessel versus multi-vessel revascularisation in ST-elevation myocardial infarction: major adverse cardiac events during long-term follow-up. Heart . 2010;96:662– 667. 7. Smits PC, Abdel-Wahab M, Neumann FJ, et al. Fractional flow reserveguided multivessel angioplasty in myocardial infarction. N Engl J Med . 2017;376:1234–1244. 8. Wald DS, Morris JK, Wald NJ, et al. Randomized trial of preventive angio plasty in myocardial infarction. N Engl J Med . 2013;369:1115–1123. 9. Mehta SR, Wang J, Wood DA, et al. Complete revascularization vs culprit lesion-only percutaneous coronary intervention for angina-related quality of life in patients with ST-segment Elevation myocardial infarction: results from the COMPLETE randomized clinical trial. JAMA Cardiol . 2022;7:1091– 1099. 10. Diletti R, den Dekker WK, Bennett J, et al. Immediate versus staged com plete revascularisation in patients presenting with acute coronary syndrome and multivessel coronary disease (BIOVASC): a prospective, open-label, non-inferiority, randomised trial. Lancet . 2023;401:1172–1182. 11. Stahli BE, Varbella F, Linke A, et al. Timing of complete revascularization with multivessel PCI for myocardial infarction. N Engl J Med . 2023;389:1368– 1379. 12. Maqsood MH, Tamis-Holland JE, Rao SV, et al. Culprit-only revasculariza tion, single-setting complete revascularization, and staged complete re vascularization in acute myocardial infarction: insights from a mixed treat ment comparison meta-analysis of randomized trials. Circ Cardiovasc Interv . 2024;17:e013737. 13. Thiele H, Akin I, Sandri M, et al. PCI strategies in patients with acute myocar dial infarction and cardiogenic shock. N Engl J Med . 2017;377:2419–2432. 14. Thiele H, Akin I, Sandri M, et al. One-year outcomes after PCI strategies in cardiogenic shock. N Engl J Med . 2018;379:1699–1710. 15. Kolte D, Sardar P, Khera S, et al. Culprit vessel-only versus multivessel per cutaneous coronary intervention in patients with cardiogenic shock com plicating ST-segment-elevation myocardial infarction: a collaborative metaanalysis. Circ Cardiovasc Interv . 2017;10:e005582. 16. Lawton JS, Tamis-Holland JE, Bangalore S, et al. 2021 ACC/AHA/SCAI guideline for coronary artery revascularization: a report of the American Col lege of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation . 2022;145:e18–e114. 17. Puymirat E, Cayla G, Simon T, et al. Multivessel PCI guided by FFR or angi ography for myocardial infarction. N Engl J Med . 2021;385:297–308. 18. Lee JM, Kim HK, Park KH, et al. Fractional flow reserve versus angiogra phy-guided strategy in acute myocardial infarction with multivessel disease: a randomized trial. Eur Heart J . 2023;44:473–484. 19. Reddy RK, Howard JP, Jamil Y, et al. Percutaneous coronary revasculariza tion strategies after myocardial infarction: a systematic review and network meta-analysis. J Am Coll Cardiol . 2024;84:276–294. 20. Farkouh ME, Domanski M, Sleeper LA, et al. Strategies for multivessel re vascularization in patients with diabetes. N Engl J Med . 2012;367:2375– 2384. 21. Kappetein AP, Head SJ, Morice MC, et al. Treatment of complex coronary artery disease in patients with diabetes: 5-year results comparing outcomes of bypass surgery and percutaneous coronary intervention in the SYNTAX trial. Eur J Cardiothorac Surg . 2013;43:1006–1013. 22. Head SJ, Milojevic M, Daemen J, et al. Mortality after coronary artery by pass grafting versus percutaneous coronary intervention with stenting for coronary artery disease: a pooled analysis of individual patient data. Lancet . 2018;391:939–948. 23. Morice MC, Serruys PW, Kappetein AP, et al. Five-year outcomes in patients with left main disease treated with either percutaneous coronary interven tion or coronary artery bypass grafting in the synergy between percutane ous coronary intervention with taxus and cardiac surgery trial. Circulation . 2014;129:2388–2394. 24. Mohr FW, Morice MC, Kappetein AP, et al. Coronary artery bypass graft surgery versus percutaneous coronary intervention in patients with threevessel disease and left main coronary disease: 5-year follow-up of the ran domised, clinical SYNTAX trial. Lancet . 2013;381:629–638.

7.4.2. Management of Multivessel CAD in NSTE-ACS

1. Biscaglia S, Guiducci V, Escaned J, et al. Complete or culprit-only PCI in older patients with myocardial infarction. N Engl J Med . 2023;389:889– 898. 2. Rathod KS, Koganti S, Jain AK, et al. Complete versus culprit-only lesion intervention in patients with acute coronary syndromes. J Am Coll Cardiol . 2018;72:1989–1999. 3. Siebert VR, Borgaonkar S, Jia X, et al. Meta-analysis comparing multi vessel versus culprit coronary arterial revascularization for patients with non-ST-segment elevation acute coronary syndromes. Am J Cardiol . 2019;124:1501–1511. 4. Sardella G, Lucisano L, Garbo R, et al. Single-staged compared with multistaged PCI in multivessel NSTEMI patients: the SMILE trial. J Am Coll Car diol . 2016;67:264–272. 5. Diletti R, den Dekker WK, Bennett J, et al. Immediate versus staged com plete revascularisation in patients presenting with acute coronary syndrome and multivessel coronary disease (BIOVASC): a prospective, open-label, non-inferiority, randomised trial. Lancet . 2023;401:1172–1182. 6. Reddy RK, Howard JP, Jamil Y, et al. Percutaneous coronary revasculariza tion strategies after myocardial infarction: a systematic review and network meta-analysis. J Am Coll Cardiol . 2024;84:276–294. 7. Sels JW, Tonino PA, Siebert U, et al. Fractional flow reserve in unstable angina and non-ST-segment elevation myocardial infarction experience from the FAME (Fractional flow reserve versus Angiography for Multivessel Evaluation) study. J Am Coll Cardiol Intv . 2011;4:1183–1189. 8. Layland J, Oldroyd KG, Curzen N, et al. Fractional flow reserve vs. angi ography in guiding management to optimize outcomes in non-ST-segment elevation myocardial infarction: the British Heart Foundation FAMOUSNSTEMI randomized trial. Eur Heart J . 2015;36:100–111. 9. Lee JM, Kim HK, Park KH, et al. Fractional flow reserve versus angiogra phy-guided strategy in acute myocardial infarction with multivessel disease: a randomized trial. Eur Heart J . 2023;44:473–484. 10. Thiele H, Akin I, Sandri M, et al. PCI strategies in patients with acute myo cardial infarction and cardiogenic shock. N Engl J Med . 2017;377:2419– 2432. 11. Thiele H, Akin I, Sandri M, et al. One-year outcomes after PCI strategies in cardiogenic shock. N Engl J Med . 2018;379:1699–1710. 12. Lawton JS, Tamis-Holland JE, Bangalore S, et al. 2021 ACC/AHA/SCAI guideline for coronary artery revascularization: a report of the American Col lege of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation . 2022;145:e18–e114. 13. Heitner JF, Senthilkumar A, Harrison JK, et al. Identifying the infarct-related artery in patients with non-ST-segment-elevation myocardial infarction. Circ Cardiovasc Interv . 2019;12:e007305. 14. Deleted in proof. 15. Brener SJ, Milford-Beland S, Roe MT, et al. Culprit-only or multivessel re vascularization in patients with acute coronary syndromes: an American Col lege of Cardiology National Cardiovascular Database Registry report. Am Heart J . 2008;155:140–146. 16. Hanratty CG, Koyama Y, Rasmussen HH, et al. Exaggeration of nonculprit stenosis severity during acute myocardial infarction: implications for imme diate multivessel revascularization. J Am Coll Cardiol . 2002;40:911–916. 17. Van Belle E, Baptista SB, Raposo L, et al. Impact of routine fractional flow reserve on management decision and 1-year clinical outcome of patients with acute coronary syndromes: PRIME-FFR (Insights from the POST-IT [Portuguese Study on the Evaluation of FFR-Guided Treatment of Coronary Disease] and R3F [French FFR Registry] Integrated Multicenter RegistriesImplementation of FFR [Fractional Flow Reserve] in Routine Practice). Circ Cardiovasc Interv . 2017;10:e004296. 18. Head SJ, Milojevic M, Daemen J, et al. Mortality after coronary artery by pass grafting versus percutaneous coronary intervention with stenting for coronary artery disease: a pooled analysis of individual patient data. Lancet . 2018;391:939–948. 19. Sabatine MS, Bergmark BA, Murphy SA, et al. Percutaneous coronary inter vention with drug-eluting stents versus coronary artery bypass grafting in left main coronary artery disease: an individual patient data meta-analysis. Lancet . 2021;398:2247–2257. 20. Farkouh ME, Domanski M, Sleeper LA, et al. Strategies for multivessel re vascularization in patients with diabetes. N Engl J Med . 2012;367:2375– 2384. 21. Velazquez EJ, Lee KL, Jones RH, et al. Coronary-artery bypass surgery in patients with ischemic cardiomyopathy. N Engl J Med . 2016;374:1511– 1520. 22. Parikh SV, de Lemos JA, Jessen ME, et al. Timing of in-hospital coronary artery bypass graft surgery for non-ST-segment elevation myocardial in farction patients results from the National Cardiovascular Data Registry ACTION Registry-GWTG (Acute Coronary Treatment and Intervention Out comes Network Registry-Get With The Guidelines). J Am Coll Cardiol Intv . 2010;3:419–427. 23. Davierwala PM, Verevkin A, Leontyev S, et al. Does timing of coronary artery bypass surgery affect early and long-term outcomes in patients with nonST-segment-elevation myocardial infarction? Circulation . 2015;132:731– 740. 24. Nichols EL, McCullough JN, Ross CS, et al. Optimal timing from myocardial infarction to coronary artery bypass grafting on hospital mortality. Ann Tho rac Surg . 2017;103:162–171. 25. Elscot JJ, Kakar H, Scarparo P, et al. Timing of complete multivessel re vascularization in patients presenting with non-ST-segment elevation acute coronary syndrome. J Am Coll Cardiol Intv . 2024;17:771–782.

8.1. Revascularization in ACS With Cardiogenic Shock

1. Scholz KH, Maier SKG, Maier LS, et al. Impact of treatment delay on mortal ity in ST-segment elevation myocardial infarction (STEMI) patients present ing with and without haemodynamic instability: results from the German pro spective, multicentre FITT-STEMI trial. Eur Heart J . 2018;39:1065–1074. 2. Hochman JS, Sleeper LA, Webb JG, et al. Early revascularization in acute myocardial infarction complicated by cardiogenic shock. SHOCK Investiga tors. Should we emergently revascularize occluded coronaries for cardio genic shock. N Engl J Med . 1999;341:625–634. 3. Axelsson TA, Mennander A, Malmberg M, et al. Is emergency and sal vage coronary artery bypass grafting justified? The Nordic emergency/ salvage coronary artery bypass grafting study. Eur J Cardiothorac Surg 2016;49:1451–1456. 4. Liakopoulos OJ, Schlachtenberger G, Wendt D, et al. Early clinical outcomes of surgical myocardial revascularization for acute coronary syndromes com plicated by cardiogenic shock: a report from the North-Rhine-Westphalia Surgical Myocardial Infarction Registry. J Am Heart Assoc . 2019;8:e012049. 5. Thiele H, Akin I, Sandri M, et al. PCI strategies in patients with acute myocar dial infarction and cardiogenic shock. N Engl J Med . 2017;377:2419–2432. 6. Thiele H, Akin I, Sandri M, et al. One-year outcomes after PCI strategies in cardiogenic shock. N Engl J Med . 2018;379:1699–1710. 7. Kolte D, Sardar P, Khera S, et al. Culprit vessel-only versus multivessel per cutaneous coronary intervention in patients with cardiogenic shock com plicating ST-segment-elevation myocardial infarction: a collaborative metaanalysis. Circ Cardiovasc Interv . 2017;10:e005582. 8. Lawton JS, Tamis-Holland JE, Bangalore S, et al. 2021 ACC/AHA/SCAI guideline for coronary artery revascularization: a report of the American Col lege of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation . 2022;145:e18–e114. 9. Mehta RH, Lopes RD, Ballotta A, et al. Percutaneous coronary intervention or coronary artery bypass surgery for cardiogenic shock and multivessel coronary artery disease? Am Heart J . 2010;159:141–147. 10. Hochman JS, Sleeper LA, White HD, et al. One-year survival following early revascularization for cardiogenic shock. JAMA . 2001;285:190–192. 11. Hochman JS, Sleeper LA, Webb JG, et al. Early revascularization and longterm survival in cardiogenic shock complicating acute myocardial infarction. JAMA . 2006;295:2511–2515. 12. Smilowitz NR, Alviar CL, Katz SD, Hochman JS. Coronary artery bypass grafting versus percutaneous coronary intervention for myocardial infarction complicated by cardiogenic shock. Am Heart J . 2020;226:255–263.

8.2. MCS in Patients With ACS and Cardiogenic Shock

1. Moller JE, Engstrom T, Jensen LO, et al. Microaxial flow pump or standard care in infarct-related cardiogenic shock. N Engl J Med . 2024;390:1382– 1393. 2. Ronco D, Matteucci M, Ravaux JM, et al. Mechanical circulatory support as a bridge to definitive treatment in post-infarction ventricular septal rupture. J Am Coll Cardiol Intv . 2021;14:1053–1066. 3. Matteucci M, Fina D, Jiritano F, et al. The use of extracorporeal membrane oxygenation in the setting of postinfarction mechanical complications: out come analysis of the Extracorporeal Life Support Organization Registry. Interact Cardiovasc Thorac Surg . 2020;31:369–374. 4. Elbadawi A, Elgendy IY, Mahmoud K, et al. Temporal trends and outcomes of mechanical complications in patients with acute myocardial infarction. J Am Coll Cardiol Intv . 2019;12:1825–1836. 5. Thiele H, Zeymer U, Neumann FJ, et al. Intraaortic balloon support for myo cardial infarction with cardiogenic shock. N Engl J Med . 2012;367:1287– 1296. 6. Thiele H, Zeymer U, Neumann FJ, et al. Intra-aortic balloon counterpulsation in acute myocardial infarction complicated by cardiogenic shock (IABPSHOCK II): final 12 month results of a randomised, open-label trial. Lancet . 2013;382:1638–1645. 7. Thiele H, Zeymer U, Thelemann N, et al. Intraaortic balloon pump in cardio genic shock complicating acute myocardial infarction: long-term 6-year out come of the randomized IABP-SHOCK II trial. Circulation . 2019;139:395– 403. 8. Ostadal P, Rokyta R, Karasek J, et al. Extracorporeal membrane oxygenation in the therapy of cardiogenic shock: results of the ECMO-CS randomized clinical trial. Circulation . 2023;147:454–464. 9. Thiele H, Zeymer U, Akin I, et al. Extracorporeal life support in infarct-related cardiogenic shock. N Engl J Med . 2023;389:1286–1297. 10. Helgestad OKL, Josiassen J, Hassager C, et al. Temporal trends in inci dence and patient characteristics in cardiogenic shock following acute myo cardial infarction from 2010 to 2017: a Danish cohort study. Eur J Heart Fail . 2019;21:1370–1378. 11. Jentzer JC, van Diepen S, Barsness GW, et al. Cardiogenic shock classifica tion to predict mortality in the cardiac intensive care unit. J Am Coll Cardiol . 2019;74:2117–2128. 12. Dhruva SS, Ross JS, Mortazavi BJ, et al. Association of use of an intravascu lar microaxial left ventricular assist device vs intra-aortic balloon pump with in-hospital mortality and major bleeding among patients with acute myocar dial infarction complicated by cardiogenic shock. JAMA . 2020;323:734–745. 13. Miller PE, Bromfield SG, Ma Q, et al. Clinical outcomes and cost as sociated with an intravascular microaxial left ventricular assist device vs intra-aortic balloon pump in patients presenting with acute myo cardial infarction complicated by cardiogenic shock. JAMA Intern Med . 2022;182:926–933. 14. Bochaton T, Huot L, Elbaz M, et al. Mechanical circulatory support with the Impella® LP5.0 pump and an intra-aortic balloon pump for cardiogenic shock in acute myocardial infarction: the IMPELLA-STIC randomized study. Arch Cardiovasc Dis . 2020;113:237–243. 15. Ouweneel DM, Eriksen E, Seyfarth M, Henriques JP. Percutaneous me chanical circulatory support versus intra-aortic balloon pump for treat ing cardiogenic shock: meta-analysis. J Am Coll Cardiol . 2017;69:358– 360. 16. Seyfarth M, Sibbing D, Bauer I, et al. A randomized clinical trial to evaluate the safety and efficacy of a percutaneous left ventricular assist device ver sus intra-aortic balloon pumping for treatment of cardiogenic shock caused by myocardial infarction. J Am Coll Cardiol . 2008;52:1584–1588. 17. Seto AH, Abu-Fadel MS, Sparling JM, et al. Real-time ultrasound guid ance facilitates femoral arterial access and reduces vascular complications: FAUST (Femoral Arterial Access With Ultrasound Trial). J Am Coll Cardiol Intv . 2010;3:751–758. 18. Sobolev M, Slovut DP, Lee Chang A, et al. Ultrasound-guided catheterization of the femoral artery: a systematic review and meta-analysis of randomized controlled trials. J Invasive Cardiol . 2015;27:318–323. 19. Jolly SS, AlRashidi S, d’Entremont MA, et al. Routine ultrasonography guid ance for femoral vascular access for cardiac procedures: the UNIVERSAL randomized clinical trial. JAMA Cardiol . 2022;7:1110–1118. 20. Hochman JS, Sleeper LA, Webb JG, et al. Early revascularization in acute myocardial infarction complicated by cardiogenic shock. SHOCK Investiga tors. Should we emergently revascularize occluded coronaries for cardio genic shock. N Engl J Med . 1999;341:625–634. 21. Zeymer U, Freund A, Hochadel M, et al. Venoarterial extracorporeal mem brane oxygenation in patients with infarct-related cardiogenic shock: an individual patient data meta-analysis of randomised trials. Lancet . 2023;402:1338–1346.

9.1. Mechanical Complications

1. Ronco D, Matteucci M, Ravaux JM, et al. Mechanical circulatory support as a bridge to definitive treatment in post-infarction ventricular septal rupture. J Am Coll Cardiol Intv . 2021;14:1053–1066. 2. Matteucci M, Fina D, Jiritano F, et al. The use of extracorporeal membrane oxygenation in the setting of postinfarction mechanical complications: out come analysis of the Extracorporeal Life Support Organization Registry. Interact Cardiovasc Thorac Surg . 2020;31:369–374. 3. Elbadawi A, Elgendy IY, Mahmoud K, et al. Temporal trends and outcomes of mechanical complications in patients with acute myocardial infarction. J Am Coll Cardiol Intv . 2019;12:1825–1836. 4. Deleted in proof. 5. French JK, Hellkamp AS, Armstrong PW, et al. Mechanical complications after percutaneous coronary intervention in ST-elevation myocardial infarc tion (from APEX-AMI). Am J Cardiol . 2010;105:59–63. 6. Lemery R, Smith HC, Giuliani ER, Gersh BJ. Prognosis in rupture of the ventricular septum after acute myocardial infarction and role of early surgi cal intervention. Am J Cardiol . 1992;70:147–151. 7. Crenshaw BS, Granger CB, Birnbaum Y, et al. Risk factors, angiographic patterns, and outcomes in patients with ventricular septal defect complicat ing acute myocardial infarction. GUSTO-I (Global Utilization of Streptoki nase and TPA for Occluded Coronary Arteries) Trial Investigators. Circula tion . 2000;101:27–32. 8. Kilic A, Sultan I, Chu D, et al. Mitral valve surgery for papillary muscle rupture: outcomes in 1342 patients from the Society of Thoracic Surgeons data base. Ann Thorac Surg . 2020;110:1975–1981. 9. Matteucci M, Ronco D, Ravaux JM, et al. Surgical repair of post-infarction ventricular free-wall rupture in the Netherlands: data from a nationwide reg istry. Ann Cardiothorac Surg . 2022;11:310–318. 10. Menon V, Webb JG, Hillis LD, et al. Outcome and profile of ventricu lar septal rupture with cardiogenic shock after myocardial infarction: a report from the SHOCK Trial Registry. Should we emergently revas cularize occluded coronaries in cardiogenic shock? J Am Coll Cardiol . 2000;36:1110–1116. 11. Jones BM, Kapadia SR, Smedira NG, et al. Ventricular septal rupture com plicating acute myocardial infarction: a contemporary review. Eur Heart J . 2014;35:2060–2068. 12. Sakaguchi G, Miyata H, Motomura N, et al. Surgical repair of post-infarction ventricular septal defect- findings from a Japanese national database. Circ J . 2019;83:2229–2235. 13. Arnaoutakis GJ, Zhao Y, George TJ, et al. Surgical repair of ventricular septal defect after myocardial infarction: outcomes from the Society of Thoracic Surgeons National Database. Ann Thorac Surg . 2012;94:436–443; discus sion 443–434. 14. Morimura H, Tabata M. Delayed surgery after mechanical circulatory sup port for ventricular septal rupture with cardiogenic shock. Interact Cardiovasc Thorac Surg . 2020;31:868–873. 15. Furui M, Sakurai Y, Kakii B, et al. Benefits and risks of delayed surgery for ventricular septal rupture after acute myocardial infarction. Int Heart J . 2022;63:433–440. 16. Schlotter F, de Waha S, Eitel I, et al. Interventional post-myocardial infarction ventricular septal defect closure: a systematic review of current evidence. EuroIntervention . 2016;12:94–102. 17. Giblett JP, Matetic A, Jenkins D, et al. Post-infarction ventricular septal de fect: percutaneous or surgical management in the UK national registry. Eur Heart J . 2022;43:5020–5032. 18. Perez-Villa B, Cubeddu RJ, Brozzi N, et al. Transition to heart transplantation in post-myocardial infarction ventricular septal rupture: a systematic review. Heart Fail Rev . 2023;28:217–227. 19. Morrow DA, Fang JC, Fintel DJ, et al. Evolution of critical care cardiology: transformation of the cardiovascular intensive care unit and the emerging need for new medical staffing and training models: a scientific statement from the American Heart Association. Circulation . 2012;126:1408–1428. 20. Papolos AI, Kenigsberg BB, Berg DD, et al. Management and outcomes of cardiogenic shock in cardiac ICUs with versus without shock teams. J Am Coll Cardiol . 2021;78:1309–1317. 21. Tehrani BN, Truesdell AG, Sherwood MW, et al. Standardized team-based care for cardiogenic shock. J Am Coll Cardiol . 2019;73:1659–1669. 22. Slater J, Brown RJ, Antonelli TA, et al. Cardiogenic shock due to cardiac free-wall rupture or tamponade after acute myocardial infarction: a report from the SHOCK Trial Registry. Should we emergently revascularize occlud ed coronaries for cardiogenic shock? J Am Coll Cardiol . 2000;36:1117– 1122. 23. Thompson CR, Buller CE, Sleeper LA, et al. Cardiogenic shock due to acute severe mitral regurgitation complicating acute myocardial infarc tion: a report from the SHOCK Trial Registry. Should we use emergently revascularize occluded coronaries in cardiogenic shock? J Am Coll Cardiol . 2000;36:1104–1109. 24. Valle JA, Miyasaka RL, Carroll JD. Acute mitral regurgitation secondary to papillary muscle tear: is transcatheter edge-to-edge mitral valve repair a new paradigm? Circ Cardiovasc Interv . 2017;10:e005050. 25. Thiele H, Lauer B, Hambrecht R, et al. Short and long-term hemodynamic effects of intra-aortic balloon support in ventricular septal defect complicat ing acute myocardial infarction. Am J Cardiol . 2003;92:450–454. 26. Damluji AA, van Diepen S, Katz JN, et al. Mechanical complications of acute myocardial infarction: a scientific statement from the American Heart As sociation. Circulation . 2021;144:e16–e35.

9.2. Electrical Complications and Prevention of Sudden Cardiac Death After ACS

1. Moss AJ, Hall WJ, Cannom DS, et al. Improved survival with an implanted defibrillator in patients with coronary disease at high risk for ventricular ar rhythmia. N Engl J Med . 1996;335:1933–1940. 2. Moss AJ, Zareba W, Hall WJ, et al. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med . 2002;346:877–883. 3. Bardy GH, Lee KL, Mark DB, et al. Amiodarone or an implantable cardiovert er-defibrillator for congestive heart failure. N Engl J Med . 2005;352:225– 237. 4. Buxton AE, Lee KL, Fisher JD, et al. A randomized study of the prevention of sudden death in patients with coronary artery disease. Multicenter Un sustained Tachycardia Trial Investigators. N Engl J Med . 1999;341:1882– 1890. 5. Solomon SD, Zelenkofske S, McMurray JJ, et al. Sudden death in patients with myocardial infarction and left ventricular dysfunction, heart failure, or both. N Engl J Med . 2005;352:2581–2588. 6. Zaman S, Sivagangabalan G, Narayan A, et al. Outcomes of early risk strati fication and targeted implantable cardioverter-defibrillator implantation after ST-elevation myocardial infarction treated with primary percutaneous coro nary intervention. Circulation . 2009;120:194–200. 7. Olgin JE, Pletcher MJ, Vittinghoff E, et al. Wearable cardioverter-defibrillator after myocardial infarction. N Engl J Med . 2018;379:1205–1215. 8. Kim H-L, Kim S-H, Seo J-B, et al. Influence of second-and third-degree heart block on 30-day outcome following acute myocardial infarction in the drug-eluting stent era. Am J Cardiol . 2014;114:1658–1662. 9. Wang P, Wang S, Liu Z, et al. Prognostic value of temporary pacemaker insertion in patients with acute myocardial infarction in the era of percutane ous coronary revascularization. Rev Cardiovasc Med . 2023;24:179. 10. Joglar JA, Chung MK, Armbruster AL, et al. 2023 ACC/AHA/ACCP/ HRS guideline for the diagnosis and management of atrial fibrillation: a report of the American College of ardiology/American Heart As sociation Joint Committee on Clinical Practice Guidelines. Circulation . 2024;149:e1–e156. 11. Thomsen AF, Jacobsen PK, Koeber L, et al. Risk of arrhythmias after myo cardial infarction in patients with left ventricular systolic dysfunction accord ing to mode of revascularization: a Cardiac Arrhythmias and RIsk Strati fication after Myocardial infArction (CARISMA) substudy. EP: Europace . 2021;23:616–623. 12. Rymer JA, Wegermann ZK, Wang TY, et al. Ventricular arrhythmias after primary percutaneous coronary intervention for STEMI. JAMA Netw Open . 2024;7:e2410288. 13. Buxton AE, Lee KL, DiCarlo L, et al. Electrophysiologic testing to identify patients with coronary artery disease who are at risk for sudden death. Multicenter Unsustained Tachycardia Trial Investigators. N Engl J Med . 2000;342:1937–1945. 14. Bigger JT Jr, CABG Patch Trial Investigators. Prophylactic use of implanted cardiac defibrillators in patients at high risk for ventricular arrhythmias after coronary-artery bypass graft surgery. Coronary Artery Bypass Graft (CABG) Patch Trial Investigators. N Engl J Med . 1997;337:1569–1575. 15. Hohnloser SH, Kuck KH, Dorian P, et al. Prophylactic use of an implantable cardioverter-defibrillator after acute myocardial infarction. N Engl J Med . 2004;351:2481–2488. 16. Steinbeck G, Andresen D, Seidl K, et al. Defibrillator implantation early after myocardial infarction. N Engl J Med . 2009;361:1427–1436. 17. Podolecki T, Lenarczyk R, Kowalczyk J, et al. Prognostic significance of complex ventricular arrhythmias complicating ST-segment elevation myo cardial infarction. Am J Cardiol . 2018;121:805–809. 18. Kusumoto FM, Calkins H, Boehmer J, et al. HRS/ACC/AHA expert consen sus statement on the use of implantable cardioverter-defibrillator therapy in patients who are not included or not well represented in clinical trials. Circulation . 2014;130:94–125. 19. Komatsu Y, Hocini M, Nogami A, et al. Catheter ablation of refrac tory ventricular fibrillation storm after myocardial infarction. Circulation . 2019;139:2315–2325. 20. Kusumoto FM, Schoenfeld MH, Barrett C, et al. 2018 ACC/AHA/HRS guideline on the evaluation and management of patients with bradycardia and cardiac conduction delay: a report of the American College of Cardiol ogy/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Circulation . 2019;140:e382–e482. 21. Olgin JE, Lee BK, Vittinghoff E, et al. Impact of wearable cardioverter-de fibrillator compliance on outcomes in the VEST trial: as-treated and perprotocol analyses. J Cardiovasc Electrophysiol . 2020;31:1009–1018. 22. Kim KH, Jeong MH, Ahn Y, et al. Differential clinical implications of highdegree atrioventricular block complicating ST-segment elevation myocardial infarction according to the location of infarction in the era of primary percu taneous coronary intervention. Korean Circ J . 2016;46:315–323. 23. Auffret V, Loirat A, Leurent G, et al. High-degree atrioventricular block com plicating ST segment elevation myocardial infarction in the contemporary era. Heart . 2016;102:40–49. 24. Aguiar Rosa S, Timoteo AT, Ferreira L, et al. Complete atrioventricular block in acute coronary syndrome: prevalence, characterisation and implication on outcome. Eur Heart J Acute Cardiovasc Care . 2018;7:218–223. 25. Gang UJ, Hvelplund A, Pedersen S, et al. High-degree atrioventricular block complicating ST-segment elevation myocardial infarction in the era of pri mary percutaneous coronary intervention. Europace . 2012;14:1639–1645. 26. Alnsasra H, Ben-Avraham B, Gottlieb ${\mathsf{S}},$ et al. High-grade atrioventricular block in patients with acute myocardial infarction. Insights from a contem porary multi-center survey. J Electrocardiol . 2018;51:386–391. 27. Singh SM, FitzGerald G, Yan AT, et al. High-grade atrioventricular block in acute coronary syndromes: insights from the Global Registry of Acute Coro nary Events. Eur Heart J . 2015;36:976–983. 28. Pokorney SD, Radder C, Schulte PJ, et al. High-degree atrioventricular block, asystole, and electro-mechanical dissociation complicating non-STsegment elevation myocardial infarction. Am Heart J . 2016;171:25–32. 29. Hynes JK, Holmes DR Jr, Harrison CE. Five-year experience with temporary pacemaker therapy in the coronary care unit. Mayo Clin Proc . 1983:122–126.

9.3. Pericarditis Management After MI

1. Gouriet F, Levy PY, Casalta JP, et al. Etiology of pericarditis in a prospective cohort of 1162 cases. Am J Med . 2015;128:784.e781–e788. 2. Imazio M, Brucato A, Rovere ME, et al. Contemporary features, risk fac tors, and prognosis of the post-pericardiotomy syndrome. Am J Cardiol . 2011;108:1183–1187. 3. Imazio M, Negro A, Belli R, et al. Frequency and prognostic significance of pericarditis following acute myocardial infarction treated by primary percu taneous coronary intervention. Am J Cardiol . 2009;103:1525–1529. 4. Berman J, Haffajee CI, Alpert JS. Therapy of symptomatic pericarditis after myocardial infarction: retrospective and prospective studies of as pirin, indomethacin, prednisone, and spontaneous resolution. Am Heart J . 1981;101:750–753. 5. Imazio M, Bobbio M, Cecchi E, et al. Colchicine as first-choice therapy for recurrent pericarditis: results of the CORE (COlchicine for REcurrent peri carditis) trial. Arch Intern Med . 2005;165:1987–1991. 6. Imazio M, Brucato A, Cemin R, et al. Colchicine for recurrent pericarditis (CORP): a randomized trial. Ann Intern Med . 2011;155:409–414. 7. Imazio M, Belli R, Brucato A, et al. Efficacy and safety of colchicine for treat ment of multiple recurrences of pericarditis (CORP-2): a multicentre, dou ble-blind, placebo-controlled, randomised trial. Lancet . 2014;383:2232– 2237. 8. Imazio M, Brucato A, Cemin R, et al. A randomized trial of colchicine for acute pericarditis. N Engl J Med . 2013;369:1522–1528. 9. Imazio M, Bobbio M, Cecchi E, et al. Colchicine in addition to conventional therapy for acute pericarditis: results of the COlchicine for acute PEricardi tis (COPE) trial. Circulation . 2005;112:2012–2016. 10. Meurin P, Tabet JY, Thabut G, et al. Nonsteroidal anti-inflammatory drug treatment for postoperative pericardial effusion: a multicenter randomized, double-blind trial. Ann Intern Med . 2010;152:137–143. 11. Meurin P, Lelay-Kubas S, Pierre B, et al. Colchicine for postoperative peri cardial effusion: a multicentre, double-blind, randomised controlled trial. Heart . 2015;101:1711–1716. 12. Bulkley BH, Roberts WC. Steroid therapy during acute myocardial infarc tion. A cause of delayed healing and of ventricular aneurysm. Am J Med . 1974;56:244–250. 13. Silverman HS, Pfeifer MP. Relation between use of anti-inflammatory agents and left ventricular free wall rupture during acute myocardial infarc tion. Am J Cardiol . 1987;59:363–364.

9.4. Management of LV Thrombus After MI

1. Camaj A, Fuster V, Giustino G, et al. Left ventricular thrombus following acute myocardial infarction: JACC state-of-the-art review. J Am Coll Cardiol . 2022;79:1010–1022. 2. Bulluck H, Chan MHH, Paradies V, et al. Incidence and predictors of left ventricular thrombus by cardiovascular magnetic resonance in acute STsegment elevation myocardial infarction treated by primary percutane ous coronary intervention: a meta-analysis. J Cardiovasc Magn Reson . 2018;20:72. 3. McCarthy CP, Vaduganathan M, McCarthy KJ, et al. Left ventricular throm bus after acute myocardial infarction: screening, prevention, and treatment. JAMA Cardiol . 2018;3:642–649. 4. Massussi M, Scotti A, Lip GYH, et al. Left ventricular thrombosis: new perspectives on an old problem. Eur Heart J Cardiovasc Pharmacother . 2021;7:158–167. 5. Gellen B, Biere L, Logeart D, et al. Timing of cardiac magnetic reso nance imaging impacts on the detection rate of left ventricular throm bus after myocardial infarction. J Am Coll Cardiol Img . 2017;10:1404– 1405. 6. Levine GN, McEvoy JW, Fang JC, et al. Management of patients at risk for and with left ventricular thrombus: a scientific statement from the American Heart Association. Circulation . 2022;146:e205–e223.

10.1. Cardiac Intensive Care Unit

1. Winkler C, Funk M, Schindler DM, et al. Arrhythmias in patients with acute coronary syndrome in the first 24 hours of hospitalization. Heart Lung . 2013;42:422–427. 2. Wasfy JH, Kennedy KF, Masoudi FA, et al. Predicting length of stay and the need for postacute care after acute myocardial infarction to improve healthcare efficiency. Circ Cardiovasc Qual Outcomes . 2018;11:e004635. 3. Fanaroff AC, Chen AY, Thomas LE, et al. Risk score to predict need for intensive care in initially hemodynamically stable adults with nonST-segment-elevation myocardial infarction. J Am Heart Assoc . 2018;7:e008894.

10.2. Management of Anemia in ACS

1. Carson JL, Brooks MM, Hebert PC, et al. Restrictive or liberal trans fusion strategy in myocardial infarction and anemia. N Engl J Med . 2023;389:2446–2456. 2. Vicente-Ibarra N, Marin F, Pernias-Escrig V, et al. Impact of anemia as risk factor for major bleeding and mortality in patients with acute coronary syn drome. Eur J Intern Med . 2019;61:48–53. 3. Younge JO, Nauta ST, Akkerhuis KM, et al. Effect of anemia on short- and long-term outcome in patients hospitalized for acute coronary syndromes. Am J Cardiol . 2012;109:506–510. 4. Brener SJ, Mehran R, Dangas GD, et al. Relation of baseline hemoglobin levels and adverse events in patients with acute coronary syndromes (from the Acute Catheterization and Urgent Intervention Triage strategY and Har monizing Outcomes with RevasculariZatiON and Stents in Acute Myocardial Infarction Trials). Am J Cardiol . 2017;119:1710–1716. 5. Chatterjee S, Wetterslev J, Sharma A, et al. Association of blood transfusion with increased mortality in myocardial infarction: a meta-analysis and diver sity-adjusted study sequential analysis. JAMA Intern Med . 2013;173:132– 139. 6. Rao SV, Jollis JG, Harrington RA, et al. Relationship of blood transfusion and clinical outcomes in patients with acute coronary syndromes. JAMA . 2004;292:1555–1562. 7. Alexander KP, Chen AY, Wang TY, et al. Transfusion practice and outcomes in non-ST-segment elevation acute coronary syndromes. Am Heart J . 2008;155:1047–1053. 8. Yang X, Alexander KP, Chen AY, et al. The implications of blood transfusions for patients with non-ST-segment elevation acute coronary syndromes: re sults from the CRUSADE National Quality Improvement Initiative. J Am Coll Cardiol . 2005;46:1490–1495. 9. Carson JL, Stanworth SJ, Dennis JA, et al. Transfusion thresholds for guiding red blood cell transfusion. Cochrane Database Sys Review . 2021;12:CD002042. 10. Carson JL, Stanworth SJ, Guyatt G, et al. Red blood cell transfusion: 2023 AABB international guidelines. JAMA . 2023;330:1892–1902. 11. Carson JL, Stanworth SJ, Alexander JH, et al. Clinical trials evaluating red blood cell transfusion thresholds: an updated systematic review and with additional focus on patients with cardiovascular disease. Am Heart J . 2018;200:96–101. 12. Ducrocq G, Gonzalez-Juanatey JR, Puymirat E, et al. Effect of a restrictive vs liberal blood transfusion strategy on major cardiovascular events among patients with acute myocardial infarction and anemia: the REALITY random ized clinical trial. JAMA 2021;325:552–560. 13. Gonzalez-Juanatey JR, Lemesle G, Puymirat E, et al. One-year major cardio vascular events after restrictive versus liberal blood transfusion strategy in patients with acute myocardial infarction and anemia: the REALITY random ized trial. Circulation . 2022;145:486–488.

10.3. Telemetry and Length of Stay

1. Piccini JP, White JA, Mehta RH, et al. Sustained ventricular tachycardia and ventricular fibrillation complicating non-ST-segment-elevation acute coro nary syndromes. Circulation . 2012;126:41–49. 2. Rymer JA, Wegermann ZK, Wang TY, et al. Ventricular arrhythmias after primary percutaneous coronary intervention for STEMI. JAMA Netw Open . 2024;7:e2410288. 3. De Luca G, Suryapranata H, van ‘t Hof AW, et al. Prognostic assessment of patients with acute myocardial infarction treated with primary angioplasty: implications for early discharge. Circulation . 2004;109:2737–2743. 4. Wasfy JH, Kennedy KF, Masoudi FA, et al. Predicting length of stay and the need for postacute care after acute myocardial infarction to improve healthcare efficiency. Circ Cardiovasc Qual Outcomes . 2018;11:e004635. 5. Jones DA, Rathod KS, Howard JP, et al. Safety and feasibility of hospital dis charge 2 days following primary percutaneous intervention for ST-segment elevation myocardial infarction. Heart . 2012;98:1722–1727. 6. Melberg T, Jorgensen M, Orn S, et al. Safety and health status following early discharge in patients with acute myocardial infarction treated with pri mary PCI: a randomized trial. Eur J Prev Cardiol . 2015;22:1427–1434. 7. Grines CL, Marsalese DL, Brodie B, et al. Safety and cost-effectiveness of early discharge after primary angioplasty in low risk patients with acute myocardial infarction. PAMI-II Investigators. Primary Angioplasty in Myocar dial Infarction. J Am Coll Cardiol . 1998;31:967–972. 8. Seto AH, Shroff A, Abu-Fadel M, et al. Length of stay following percutane ous coronary intervention: an expert consensus document update from the society for cardiovascular angiography and interventions. Catheter Cardio vasc Interv . 2018;92:717–731. 9. Hariri E, Kassas I, Hammoud MA, et al. Same day discharge following nonelective PCI for non-ST elevation acute coronary syndromes. Am Heart J . 2022;246:125–135. 10. Pelter MM, Adams MG, Drew BJ. Transient myocardial ischemia is an inde pendent predictor of adverse in-hospital outcomes in patients with acute coronary syndromes treated in the telemetry unit. Heart Lung . 2003;32:71– 78. 11. Rahimi K, Watzlawek S, Thiele H, et al. Incidence, time course, and predic tors of early malignant ventricular arrhythmias after non-ST-segment eleva tion myocardial infarction in patients with early invasive treatment. Eur Heart J . 2006;27:1706–1711. 12. Ottander P, Nilsson JB, Jensen SM, Naslund U. Ischemic ST-segment epi sodes during the initial 24 hours of ST elevation myocardial infarction pre dict prognosis at 1 and 5 years. J Electrocardiol . 2010;43:224–229. 13. Falun N, Nordrehaug JE, Hoff PI, et al. Evaluation of the appropriate ness and outcome of in-hospital telemetry monitoring. Am J Cardiol . 2013;112:1219–1223. 14. Sandau KE, Funk M, Auerbach A, et al. Update to practice standards for electrocardiographic monitoring in hospital settings: a scientific statement from the American Heart Association. Circulation . 2017;136:e273–e344.

10.4. Noninvasive Diagnostic Testing Prior to Hospital Discharge

1. Daneault B, Genereux P, Kirtane AJ, et al. Comparison of three-year out comes after primary percutaneous coronary intervention in patients with left ventricular ejection fraction ${<}40\%$ versus $\geq40\%$ (from the HORIZONSAMI trial). Am J Cardiol . 2013;111:12–20. 2. Dokainish H, Rajaram M, Prabhakaran D, et al. Incremental value of left ven tricular systolic and diastolic function to determine outcome in patients with acute ST-segment elevation myocardial infarction: the echocardiographic substudy of the OASIS-6 trial. Echocardiography . 2014;31:569–578. 3. Ng VG, Lansky AJ, Meller S, et al. The prognostic importance of left ven tricular function in patients with ST-segment elevation myocardial infarction: the HORIZONS-AMI trial. Eur Heart J Acute Cardiovasc Care . 2014;3:67– 77. 4. Damluji AA, van Diepen S, Katz JN, et al. Mechanical complications of acute myocardial infarction: a scientific statement from the American Heart As sociation. Circulation . 2021;144:e16–e35. 5. McCarthy CP, Vaduganathan M, McCarthy KJ, et al. Left ventricular throm bus after acute myocardial infarction: screening, prevention, and treatment. JAMA Cardiol . 2018;3:642–649. 6. Ibanez B, Aletras AH, Arai AE, et al. Cardiac MRI endpoints in myocardial infarction experimental and clinical trials: JACC Scientific Expert Panel. J Am Coll Cardiol . 2019;74:238–256. 7. Pontone G, Guaricci AI, Andreini D, et al. Prognostic stratification of patients with ST-segment-elevation myocardial infarction (PROSPECT): a cardiac magnetic resonance study. Circ Cardiovasc Imaging . 2017;10:e006428. 8. Bulluck H, Dharmakumar R, Arai AE, et al. Cardiovascular magnetic reso nance in acute ST-segment-elevation myocardial infarction: recent advanc es, controversies, and future directions. Circulation . 2018;137:1949–1964. 9. Tamis-Holland JE, Jneid H, Reynolds HR, et al. Contemporary diagnosis and management of patients with myocardial infarction in the absence of ob structive coronary artery disease: a scientific statement from the American Heart Association. Circulation . 2019;139:e891–e908.

10.5.1. Patient Education

1. Kourbelis CM, Marin TS, Foote J, et al. Effectiveness of discharge educa tion strategies versus usual care on clinical outcomes in acute coronary syndrome patients: a systematic review. JBI Evid Synth . 2020;18:309–331. 2. Feng YY, Chaves GSS, Shi W, et al. Education interventions in Chinese car diac patients on health behaviours, disease-related knowledge, and health outcomes: a systematic review and meta-analysis. Patient Educ Couns . 2021;104:1018–1029. 3. Shi W, Ghisi GLM, Zhang L, et al. Systematic review, meta-analysis and meta-regression to determine the effects of patient education on health behaviour change in adults diagnosed with coronary heart disease. J Clin Nurs . 2023;32:5300–5327. 4. Piekarz H, Langran C, Raza A, Donyai P. Medication-taking for secondary prevention of acute myocardial infarction: a thematic meta-synthesis of pa tient experiences. Open Heart . 2022;9:e001939. 5. American Heart Association. Life’s Essential 8. Accessed September, 2023. https://www.heart.org/en/healthy-living/healthy-lifestyle/lifes-essential-8.

10.5.2. Postdischarge Follow-Up and Systems of Care Coordination

1. Dreyer RP, Dharmarajan K, Kennedy KF, et al. Sex differences in 1-year all-cause rehospitalization in patients after acute myocardial infarction: a prospective observational study. Circulation . 2017;135:521–531. 2. O’Brien C, Valsdottir L, Wasfy JH, et al. Comparison of 30-day readmis sion rates after hospitalization for acute myocardial infarction in men versus women. Am J Cardiol . 2017;120:1070–1076. 3. Cholack G, Garfein J, Krallman R, et al. Predictors of early (0-7 days) and late (8-30 days) readmission in a cohort of acute coronary syndrome pa tients. Int J Med Stud . 2022;10:38–48. 4. Boulos PK, Messenger JC, Waldo SW. Readmission after ACS: burden, epi demiology, and mitigation. Curr Cardiol Rep . 2022;24:807–815. 5. Oliveira L, Costa I, Silva DGD, et al. Readmission of patients with acute coronary syndrome and determinants. Arq Bras Cardiol . 2019;113:42–49. 6. Gudnadottir GS, Gudnason T, Wilhelmson K, et al. Multimorbidity and re admissions in older people with acute coronary syndromes. Cardiology . 2022;147:121–132. 7. American College of Cardiology. Hospital to Home Initiative: Quality Cam paign. Accessed September 18, 2023. https://cvquality.acc.org/initiatives/ hospital-to-home. 8. American Heart Association. Acute Myocardial Infarction Toolkit. Accessed September 16, 2023. https://www.heart.org/en/health-topics/heart-attack/ heart-attack-tools-and-resources/acute-myocardial-infarction-toolkit. 9. Bettger JP, Alexander KP, Dolor RJ, et al. Transitional care after hospitaliza tion for acute stroke or myocardial infarction: a systematic review. Ann Intern Med . 2012;157:407–416. 10. Albert N, Gluckman, TJ, McNamara, R, et al. Abstract 102: the association of patient navigator program features and hospital strategies with process es and outcome metrics in acute myocardial infarction and heart failure. 2019. Accessed XXX. https://www.ahajournals.org/doi/10.1161/hcq.12. suppl_1.102. 11. Hoo JX, Yang YF, Tan JY, et al. Impact of multicomponent integrated care on mortality and hospitalization after acute coronary syndrome: a sys tematic review and meta-analysis. Eur Heart J Qual Care Clin Outcomes . 2023;9:258–267. 12. Virani SS, Newby LK, Arnold SV, et al. 2023 AHA/ACC/ACCP/ASPC/ NLA/PCNA guideline for the management of patients with chronic coro nary disease: a report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines. Circulation . 2023;148:e9–e119.

10.5.3. Cardiac Rehabilitation

1. Dibben G, Faulkner J, Oldridge N, et al. Exercise-based cardiac re habilitation for coronary heart disease. Cochrane Database Syst Rev . 2021;11:CD001800. 2. Anderson L, Oldridge N, Thompson DR, et al. Exercise-based cardiac reha bilitation for coronary heart disease: Cochrane systematic review and metaanalysis. J Am Coll Cardiol . 2016;67:1–12. 3. Anderson L, Thompson DR, Oldridge N, et al. Exercise-based cardiac rehabilitation for coronary heart disease. Cochrane Database Syst Rev . 2016;2016:CD001800. 4. Dibben GO, Faulkner J, Oldridge N, et al. Exercise-based cardiac rehabilita tion for coronary heart disease: a meta-analysis. Eur Heart J . 2023;44:452– 469. 5. Snoek JA, Prescott EI, van der Velde AE, et al. Effectiveness of home-based mobile guided cardiac rehabilitation as alternative strategy for nonparticipa tion in clinic-based cardiac rehabilitation among elderly patients in Europe: a randomized clinical trial. JAMA Cardiol . 2021;6:463–468. 6. Li Z, Hui Z, Zheng Y, et al. Efficacy of phase II remote home rehabilitation in patients with acute myocardial infarction after percutaneous coronary inter vention. Contrast Media Mol Imaging . 2022;2022:4634769. 7. Campo G, Tonet E, Chiaranda G, et al. Exercise intervention improves quality of life in older adults after myocardial infarction: randomised clinical trial. Heart . 2020;106:1658–1664. 8. Ritchey MD, Maresh S, McNeely J, et al. Tracking cardiac rehabilitation par ticipation and completion among Medicare beneficiaries to inform the efforts of a national initiative. Circ Cardiovasc Qual Outcomes . 2020;13:e005902. 9. Schultz WM, Kelli HM, Lisko JC, et al. Socioeconomic status and cardiovas cular outcomes: challenges and interventions. Circulation . 2018;137:2166– 2178. 10. Takura T, Ebata-Kogure N, Goto Y, et al. Cost-effectiveness of cardiac re habilitation in patients with coronary artery disease: a meta-analysis. Cardiol Res Pract . 2019;2019:1840894. 11. McMahon SR, Ades PA, Thompson PD. The role of cardiac rehabilitation in patients with heart disease. Trends Cardiovasc Med . 2017;27:420–425. 12. Grace SL, Russell KL, Reid RD, et al. Effect of cardiac rehabilitation referral strategies on utilization rates: a prospective, controlled study. Arch Intern Med . 2011;171:235–241. 13. Thomas RJ, Beatty AL, Beckie TM, et al. Home-based cardiac rehabilitation: a scientific statement from the American Association of Cardiovascular and Pulmonary Rehabilitation, the American Heart Association, and the Ameri can College of Cardiology. Circulation . 2019;140:e69–e89. 14. Nkonde-Price C, Reynolds K, Najem M, et al. Comparison of home-based vs center-based cardiac rehabilitation in hospitalization, medication adherence, and risk factor control among patients with cardiovascular disease. JAMA Netw Open . 2022;5:e2228720. 15. Huang K, Liu W, He D, et al. Telehealth interventions versus center-based cardiac rehabilitation of coronary artery disease: a systematic review and meta-analysis. Eur J Prev Cardiol . 2015;22:959–971. 16. Zeng W, Stason WB, Fournier S, et al. Benefits and costs of intensive life style modification programs for symptomatic coronary disease in Medicare beneficiaries. Am Heart J . 2013;165:785–792. 17. Freeman AM, Taub PR, Lo HC, Ornish D. Intensive cardiac rehabilitation: an underutilized resource. Curr Cardiol Rep . 2019;21:19. 18. Centers for Medicare & Medicaid Services. Intensive Cardiac Rehabilita tion (ICR) Programs. Accessed October 10, 2024. https://www.cms.gov/ medicare/coverage/approved-facilities-trials-registries/cardiac-rehab-programs. 19. Racette SB, Park LK, Rashdi ST, et al. Benefits of the first Pritikin out patient intensive cardiac rehabilitation program. J Cardiopulm Rehabil Prev . 2022;42:449–455. 20. Husaini M, Deych E, Waken RJ, et al. Intensive versus traditional car diac rehabilitation: mortality and cardiovascular outcomes in a 2016- 2020 retrospective Medicare cohort. Circ Cardiovasc Qual Outcomes . 2023;16:e010131. 21. Dibben GO, Dalal HM, Taylor RS, et al. Cardiac rehabilitation and physi cal activity: systematic review and meta-analysis. Heart . 2018;104:1394– 1402. 22. de Vries H, Kemps HM, van Engen-Verheul MM, et al. Cardiac rehabilitation and survival in a large representative community cohort of Dutch patients. Eur Heart J . 2015;36:1519–1528. 23. Williams MA, Maresh CM, Esterbrooks DJ, et al. Early exercise training in patients older than age 65 years compared with that in younger patients after acute myocardial infarction or coronary artery bypass grafting. Am J Cardiol . 1985;55:263–266. 24. Lavie CJ, Milani RV. Effects of cardiac rehabilitation programs on exercise capacity, coronary risk factors, behavioral characteristics, and quality of life in a large elderly cohort. Am J Cardiol . 1995;76:177–179. 25. Lavie CJ, Milani RV, Littman AB. Benefits of cardiac rehabilitation and ex ercise training in secondary coronary prevention in the elderly. J Am Coll Cardiol . 1993;22:678–683. 26. Stahle A, Mattsson E, Ryden L, et al. Improved physical fitness and quality of life following training of elderly patients after acute coronary events. A 1 year follow-up randomized controlled study. Eur Heart J . 1999;20:1475– 1484. 27. Beatty AL, Truong M, Schopfer DW, et al. Geographic variation in cardiac rehabilitation participation in Medicare and Veterans Affairs populations: op portunity for improvement. Circulation . 2018;137:1899–1908. 28. Li S, Fonarow GC, Mukamal K, et al. Sex and racial disparities in cardiac rehabilitation referral at hospital discharge and gaps in long-term mortality. J Am Heart Assoc . 2018;7:e008088. 29. McDonagh ST, Dalal H, Moore S, et al. Home-based versus centre-based cardiac rehabilitation. Cochrane Database Syst Rev . 2023;10:CD007130. 30. Sandesara PB, Lambert CT, Gordon NF, et al. Cardiac rehabilitation and risk reduction: time to “rebrand and reinvigorate”. J Am Coll Cardiol . 2015;65:389–395.

11.1. DAPT Strategies in the First 12 Months Postdischarge

1. Wallentin L, Becker RC, Budaj A, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med . 2009;361:1045– 1057. 2. Wiviott SD, Braunwald E, McCabe CH, et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med . 2007;357:2001– 2015. 3. Yusuf S, Zhao F, Mehta SR, et al. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med . 2001;345:494–502. 4. Fox KA, Mehta SR, Peters R, et al. Benefits and risks of the combination of clopidogrel and aspirin in patients undergoing surgical revascularization for non-ST-elevation acute coronary syndrome: the Clopidogrel in Unsta ble angina to prevent Recurrent ischemic Events (CURE) Trial. Circulation . 2004;110:1202–1208. 5. Held C, Asenblad N, Bassand JP, et al. Ticagrelor versus clopidogrel in pa tients with acute coronary syndromes undergoing coronary artery bypass surgery: results from the PLATO (Platelet Inhibition and Patient Outcomes) trial. J Am Coll Cardiol . 2011;57:672–684. 6. Smith PK, Goodnough LT, Levy JH, et al. Mortality benefit with prasugrel in the TRITON-TIMI 38 coronary artery bypass grafting cohort: risk-adjusted retrospective data analysis. J Am Coll Cardiol . 2012;60:388–396. 7. Baber U, Dangas G, Angiolillo DJ, et al. Ticagrelor alone vs. ticagrelor plus aspirin following percutaneous coronary intervention in patients with nonST-segment elevation acute coronary syndromes: TWILIGHT-ACS. Eur Heart J . 2020;41:3533–3545. 8. Ge Z, Kan J, Gao X, et al. Ticagrelor alone versus ticagrelor plus aspi rin from month 1 to month 12 after percutaneous coronary interven tion in patients with acute coronary syndromes (ULTIMATE-DAPT): a randomised, placebo-controlled, double-blind clinical trial. Lancet . 2024;403:1866–1878. 9. Hong SJ, Lee SJ, Suh Y, et al. Stopping aspirin within 1 month after stenting for ticagrelor monotherapy in acute coronary syndrome: the T-PASS ran domized noninferiority trial. Circulation . 2023;149:562–573. 10. Kim BK, Hong SJ, Cho YH, et al. Effect of ticagrelor monotherapy vs ti cagrelor with aspirin on major bleeding and cardiovascular events in pa tients with acute coronary syndrome: the TICO randomized clinical trial. JAMA . 2020;323:2407–2416. 11. Vranckx P, Valgimigli M, Odutayo A, et al. Efficacy and safety of ticagrelor monotherapy by clinical presentation: pre-specified analysis of the GLOBAL LEADERS trial. J Am Heart Assoc . 2021;10:e015560. 12. Ahn HJ, Lee SR, Choi EK, et al. Protective effect of proton-pump inhibitor against gastrointestinal bleeding in patients receiving oral anticoagulants: a systematic review and meta-analysis. Br J Clin Pharmacol . 2022;88:4676– 4687. 13. Bhatt DL, Cryer BL, Contant CF, et al. Clopidogrel with or without omepra zole in coronary artery disease. N Engl J Med . 2010;363:1909–1917. 14. Lai KC, Lam SK, Chu KM, et al. Lansoprazole for the prevention of recur rences of ulcer complications from long-term low-dose aspirin use. N Engl J Med . 2002;346:2033–2038. 15. Moayyedi P, Eikelboom JW, Bosch J, et al. Pantoprazole to prevent gas troduodenal events in patients receiving rivaroxaban and/or aspirin in a randomized, double-blind, placebo-controlled trial. Gastroenterology . 2019;157:403–412.e405. 16. Cayla G, Cuisset T, Silvain J, et al. Platelet function monitoring to adjust an tiplatelet therapy in elderly patients stented for an acute coronary syndrome (ANTARCTIC): an open-label, blinded-endpoint, randomised controlled su periority trial. Lancet . 2016;388:2015–2022. 17. Claassens DMF, Vos GJA, Bergmeijer TO, et al. A genotype-guided strategy for oral P2Y12 inhibitors in primary PCI. N Engl J Med . 2019;381:1621– 1631. 18. Cuisset T, Deharo P, Quilici J, et al. Benefit of switching dual antiplatelet therapy after acute coronary syndrome: the TOPIC (Timing of Platelet In hibition After Acute Coronary Syndrome) randomized study. Eur Heart J . 2017;38:3070–3078. 19. Kim CJ, Park MW, Kim MC, et al. Unguided de-escalation from ticagrelor to clopidogrel in stabilised patients with acute myocardial infarction under going percutaneous coronary intervention (TALOS-AMI): an investigatorinitiated, open-label, multicentre, non-inferiority, randomised trial. Lancet . 2021;398:1305–1316. 20. Sibbing D, Aradi D, Jacobshagen C, et al. Guided de-escalation of antiplate let treatment in patients with acute coronary syndrome undergoing percu taneous coronary intervention (TROPICAL-ACS): a randomised, open-label, multicentre trial. Lancet . 2017;390:1747–1757. 21. Valgimigli M, Frigoli E, Heg D, et al. Dual antiplatelet therapy after PCI in patients at high bleeding risk. N Engl J Med . 2021;385:1643–1655. 22. Mehran R, Baber U, Steg PG, et al. Cessation of dual antiplatelet treatment and cardiac events after percutaneous coronary intervention (PARIS): 2 year results from a prospective observational study. Lancet . 2013;382:1714– 1722. 23. Valgimigli M, Costa F, Lokhnygina Y, et al. Trade-off of myocardial infarc tion vs. bleeding types on mortality after acute coronary syndrome: les sons from the Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER) randomized trial. Eur Heart J . 2017;38:804–810. 24. Baber U, Mehran R, Giustino G, et al. Coronary thrombosis and major bleed ing after PCI with drug-eluting stents: risk scores from PARIS. J Am Coll Cardiol . 2016;67:2224–2234. 25. Costa F, van Klaveren D, James S, et al. Derivation and validation of the predicting bleeding complications in patients undergoing stent implanta tion and subsequent dual antiplatelet therapy (PRECISE-DAPT) score: a pooled analysis of individual-patient datasets from clinical trials. Lancet . 2017;389:1025–1034. 26. Urban P, Mehran R, Colleran R, et al. Defining high bleeding risk in pa tients undergoing percutaneous coronary intervention. Circulation . 2019;140:240–261. 27. Yeh RW, Secemsky EA, Kereiakes DJ, et al. Development and validation of a prediction rule for benefit and harm of dual antiplatelet therapy beyond

1 year after percutaneous coronary intervention. JAMA . 2016;315:1735–

1749.

28. Hahn JY, Song YB, Oh JH, et al. Effect of P2Y12 inhibitor monotherapy vs dual antiplatelet therapy on cardiovascular events in patients undergoing percutaneous coronary intervention: the SMART-CHOICE randomized clini cal trial. JAMA . 2019;321:2428–2437.

29. Watanabe H, Morimoto T, Natsuaki M, et al. Comparison of clopidogrel monotherapy after 1 to 2 months of dual antiplatelet therapy with 12

months of dual antiplatelet therapy in patients with acute coronary syn drome: the STOPDAPT-2 ACS randomized clinical trial. JAMA Cardiol . 2022;7:407–417. 30. Gurbel PA, Bliden KP, Hiatt BL, O’Connor CM. Clopidogrel for coronary stenting: response variability, drug resistance, and the effect of pretreat ment platelet reactivity. Circulation . 2003;107:2908–2913. 31. De Luca G, Damen SA, Camaro C, et al. Final results of the randomised evaluation of short-term dual antiplatelet therapy in patients with acute coronary syndrome treated with a new-generation stent (REDUCE trial). EuroIntervention . 2019;15:e990–e998. 32. Hahn JY, Song YB, Oh JH, et al. 6-month versus 12-month or longer dual antiplatelet therapy after percutaneous coronary intervention in patients with acute coronary syndrome (SMART-DATE): a randomised, open-label, non-inferiority trial. Lancet . 2018;391:1274–1284. 33. Merlini PA, Bauer KA, Oltrona L, et al. Persistent activation of coagula tion mechanism in unstable angina and myocardial infarction. Circulation . 1994;90:61–68. 34. Yusuf S, Mehta SR, Zhao F, et al. Early and late effects of clopidogrel in patients with acute coronary syndromes. Circulation . 2003;107:966–972. 35. Lawton JS, Tamis-Holland JE, Bangalore S, et al. 2021 ACC/AHA/SCAI guideline for coronary artery revascularization: a report of the American Col lege of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation . 2022;145:e18–e114. 36. Bittl JA, Baber U, Bradley SM, Wijeysundera DN. Duration of dual antiplate let therapy: a systematic review for the 2016 ACC/AHA guideline focused update on duration of dual antiplatelet therapy in patients with coronary artery disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation . 2016;134:e156–e178. 37. Mauri L, Kereiakes DJ, Yeh RW, et al. Twelve or 30 months of dual antiplate let therapy after drug-eluting stents. N Engl J Med . 2014;371:2155–2166. 38. O’Donoghue ML, Murphy SA, Sabatine MS. The safety and efficacy of as pirin discontinuation on a background of a P2Y12inhibitor in patients after percutaneous coronary intervention: a systematic review and meta-analysis. Circulation . 2020;142:538–545. 39. Baber U, Jang Y, Oliva A, et al. Safety and efficacy of ticagrelor monother apy in patients with acute coronary syndromes undergoing percutaneous coronary intervention: an individual patient data meta-analysis of TWILIGHT and TICO randomized trials. Circulation . 2024;149:574–584. 40. Valgimigli M, Gragnano F, Branca M, et al. P2Y12 inhibitor monotherapy or dual antiplatelet therapy after coronary revascularisation: individual patient level meta-analysis of randomised controlled trials. BMJ . 2021;373:n1332. 41. Valgimigli M, Gragnano F, Branca M, et al. Ticagrelor or clopidogrel mono therapy vs dual antiplatelet therapy after percutaneous coronary interven tion: a systematic review and patient-level meta-analysis. JAMA Cardiol . 2024;9:437–448. 42. Michelson AD, Frelinger AL 3rd, Braunwald E, et al. Pharmacodynamic as sessment of platelet inhibition by prasugrel vs. clopidogrel in the TRITONTIMI 38 trial. Eur Heart J . 2009;30:1753–1763. 43. Palmerini T, Della Riva D, Benedetto U, et al. Three, six, or twelve months of dual antiplatelet therapy after DES implantation in patients with or without acute coronary syndromes: an individual patient data pairwise and network meta-analysis of six randomized trials and 11 473 patients. Eur Heart J . 2017;38:1034–1043. 44. Natsuaki M, Watanabe H, Morimoto T, et al. An aspirin-free versus dual antiplatelet strategy for coronary stenting: STOPDAPT-3 randomized trial. Circulation . 2024;149:585–600. 45. Gilard M, Arnaud B, Cornily JC, et al. Influence of omeprazole on the anti platelet action of clopidogrel associated with aspirin: the randomized, dou ble-blind OCLA (Omeprazole CLopidogrel Aspirin) study. J Am Coll Cardiol . 2008;51:256–260. 46. Sibbing D, Morath T, Stegherr J, et al. Impact of proton pump inhibitors on the antiplatelet effects of clopidogrel. Thromb Haemost . 2009;101:714– 719. 47. Gargiulo G, Costa F, Ariotti S, et al. Impact of proton pump inhibitors on clinical outcomes in patients treated with a 6- or 24-month dual-antiplatelet therapy duration: insights from the PROlonging Dual-antiplatelet treatment after Grading stent-induced Intimal hyperplasia studY trial. Am Heart J . 2016;174:95–102. 48. O’Donoghue ML, Braunwald E, Antman EM, et al. Pharmacodynamic effect and clinical efficacy of clopidogrel and prasugrel with or without a protonpump inhibitor: an analysis of two randomised trials. Lancet . 2009;374:989– 997. 49. Goodman SG, Clare R, Pieper KS, et al. Association of proton pump in hibitor use on cardiovascular outcomes with clopidogrel and ticagrelor: insights from the platelet inhibition and patient outcomes trial. Circulation 2012;125:978–986. 50. Storey RF, Angiolillo DJ, Patil SB, et al. Inhibitory effects of ticagrelor com pared with clopidogrel on platelet function in patients with acute coronary syndromes: the PLATO (PLATelet inhibition and patient Outcomes) PLATE LET substudy. J Am Coll Cardiol . 2010;56:1456–1462. 51. Capodanno D, Mehran R, Krucoff MW, et al. Defining strategies of mod ulation of antiplatelet therapy in patients with coronary artery disease: a consensus document from the Academic Research Consortium. Circulation 2023;147:1933–1944. 52. Mega JL, Close SL, Wiviott SD, et al. Cytochrome p-450 polymorphisms and response to clopidogrel. N Engl J Med . 2009;360:354–362. 53. Galli M, Benenati S, Capodanno D, et al. Guided versus standard antiplatelet therapy in patients undergoing percutaneous coronary intervention: a sys tematic review and meta-analysis. Lancet . 2021;397:1470–1483. 54. Tavenier AH, Mehran R, Chiarito M, et al. Guided and unguided de-escala tion from potent P2Y12 inhibitors among patients with acute coronary syn drome: a meta-analysis. Eur Heart J Cardiovasc Pharmacother . 2022;8:492– 502. 55. Bonaca MP, Bhatt DL, Cohen M, et al. Long-term use of ticagrelor in pa tients with prior myocardial infarction. New Engl J Med . 2015;372:1791– 1800. 56. Smits PC, Frigoli E, Vranckx P, et al. Abbreviated antiplatelet therapy after coronary stenting in patients with myocardial infarction at high bleeding risk. J Am Coll Cardiol . 2022;80:1220–1237.

11.1.1. Antiplatelet Therapy in Patients on Anticoagulation Postdischarge

1. Cannon CP, Bhatt DL, Oldgren J, et al. Dual antithrombotic therapy with dabigatran after PCI in atrial fibrillation. N Engl J Med . 2017;377:1513– 1524. 2. Gibson CM, Mehran R, Bode C, et al. Prevention of bleeding in patients with atrial fibrillation undergoing PCI. N Engl J Med . 2016;375:2423–2434. 3. Lopes RD, Heizer G, Aronson R, et al. Antithrombotic therapy after acute coronary syndrome or PCI in atrial fibrillation. New Engl J Med . 2019;380:1509–1524. 4. Vranckx P, Valgimigli M, Eckardt L, et al. Edoxaban-based versus vitamin K antagonist-based antithrombotic regimen after successful coronary stent ing in patients with atrial fibrillation (ENTRUST-AF PCI): a randomised, open-label, phase 3b trial. Lancet . 2019;394:1335–1343. 5. Dewilde WJ, Oirbans T, Verheugt FW, et al. Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percu taneous coronary intervention: an open-label, randomised, controlled trial. Lancet . 2013;381:1107–1115. 6. Lawton JS, Tamis-Holland JE, Bangalore S, et al. 2021 ACC/AHA/SCAI guideline for coronary artery revascularization: a report of the American Col lege of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation . 2022;145:e18–e114. 7. Ruff CT, Giugliano RP, Braunwald E, et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrilla tion: a meta-analysis of randomised trials. Lancet . 2014;383:955–962. 8. Virani SS, Newby LK, Arnold SV, et al. 2023 AHA/ACC/ACCP/ASPC/ NLA/PCNA guideline for the management of patients with chronic coro nary disease: a report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines. Circulation . 2023;148:e9–e119. 9. Gargiulo G, Goette A, Tijssen J, et al. Safety and efficacy outcomes of dou ble vs. triple antithrombotic therapy in patients with atrial fibrillation following percutaneous coronary intervention: a systematic review and meta-analysis of non-Vitamin K antagonist oral anticoagulant-based randomized clinical trials. Eur Heart J . 2019;40:3757–3767. 10. Lopes RD, Hong H, Harskamp RE, et al. Optimal antithrombotic regimens for patients with atrial fibrillation undergoing percutaneous coronary inter vention: an updated network meta-analysis. JAMA Cardiology . 2020;5:582– 589. 11. Capodanno D, Di Maio M, Greco A, et al. Safety and efficacy of double anti thrombotic therapy with non-vitamin K antagonist oral anticoagulants in pa tients with atrial fibrillation undergoing percutaneous coronary intervention: a systematic review and meta-analysis. J Am Heart Assoc . 2020;9:e017212. 12. Gargiulo G, Cannon CP, Gibson CM, et al. Safety and efficacy of double vs. triple antithrombotic therapy in patients with atrial fibrillation with or without acute coronary syndrome undergoing percutaneous coronary intervention: a collaborative meta-analysis of non-vitamin K antagonist oral anticoagu lant-based randomized clinical trials. Eur Heart J Cardiovasc Pharmacother . 2021;7:F50–F60. 13. Galli M, Andreotti F, Porto I, Crea F. Intracranial haemorrhages vs. stent thromboses with direct oral anticoagulant plus single antiplatelet agent or triple antithrombotic therapy: a meta-analysis of randomized trials in atrial fi brillation and percutaneous coronary intervention/acute coronary syndrome patients. Europace . 2020;22:538–546. 14. Colleran R, Byrne RA, Ndrepepa G, et al. Antithrombotic therapy with or without aspirin after percutaneous coronary intervention or acute coro nary syndrome in patients taking oral anticoagulation: a meta-analysis and network analysis of randomized controlled trials. Cardiovasc Revasc Med . 2022;36:99–106. 15. Alexander JH, Wojdyla D, Vora AN, et al. Risk/benefit tradeoff of antithrom botic therapy in patients with atrial fibrillation early and late after an acute coronary syndrome or percutaneous coronary intervention: insights from AUGUSTUS. Circulation . 2020;141:1618–1627. 16. Lopes RD, Leonardi S, Wojdyla DM, et al. Stent thrombosis in patients with atrial fibrillation undergoing coronary stenting in the AUGUSTUS trial. Cir culation . 2020;141:781–783. 17. Smits PC, Frigoli E, Tijssen J, et al. Abbreviated antiplatelet therapy in pa tients at high bleeding risk with or without oral anticoagulant therapy after coronary stenting: an open-label, randomized, controlled trial. Circulation . 2021;144:1196–1211. 18. Valgimigli M, Frigoli E, Heg D, et al. Dual antiplatelet therapy after PCI in patients at high bleeding risk. N Engl J Med . 2021;385:1643–1655.

11.2. Reassessment of Lipid Levels Postdischarge

1. Benner JS, Tierce JC, Ballantyne CM, et al. Follow-up lipid tests and physi cian visits are associated with improved adherence to statin therapy. Phar macoeconomics . 2004;22 Suppl 3:13–23. 2. Baigent C, Blackwell L, Emberson J, et al. Cholesterol Treatment Trialists Collaboration. Efficacy and safety of more intensive lowering of LDL choles terol: a meta-analysis of data from 170000 participants in 26 randomised trials. Lancet . 2010;376:1670–1681. 3. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the man agement of blood cholesterol: a report of the American College of Cardiol ogy/American Heart Association Task Force on Clinical Practice Guidelines. Circulation . 2019;139:e1082–e1143. 4. Ramsaran E, Preusse P, Sundaresan D, et al. Adherence to blood cho lesterol treatment guidelines among physicians managing patients with atherosclerotic cardiovascular disease. Am J Cardiol . 2019;124:169– 175. 5. Zheutlin AR, Derington CG, Herrick JS, et al. Lipid-lowering therapy use and intensification among United States veterans following myocardial infarc tion or coronary revascularization between 2015 and 2019. Circ Cardiovasc Qual Outcomes . 2022;15:e008861. 6. Packard C, Chapman MJ, Sibartie M, et al. Intensive low-density lipoprotein cholesterol lowering in cardiovascular disease prevention: opportunities and challenges. Heart . 2021;107:1369–1375. 7. Wiviott SD, Cannon CP, Morrow DA, et al. Can low-density lipoprotein be too low? The safety and efficacy of achieving very low low-density lipoprotein with intensive statin therapy: a PROVE IT-TIMI 22 substudy. J Am Coll Car diol . 2005;46:1411–1416. 8. Giugliano RP, Wiviott SD, Blazing MA, et al. Long-term safety and ef ficacy of achieving very low levels of low-density lipoprotein choles terol: a prespecified analysis of the IMPROVE-IT trial. JAMA Cardiol . 2017;2:547–555. 9. Giugliano RP, Keech A, Murphy SA, et al. Clinical efficacy and safety of evolocumab in high-risk patients receiving a statin: secondary analysis of patients with low LDL cholesterol levels and in those already receiv ing a maximal-potency statin in a randomized clinical trial. JAMA Cardiol . 2017;2:1385–1391. 10. Cannon CP, Braunwald E, McCabe CH, et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med . 2004;350:1495–1504. 11. Lowenstern AM, Li S, Navar AM, et al. Measurement of low-density lipopro tein cholesterol levels in primary and secondary prevention patients: insights from the PALM Registry. J Am Heart Assoc . 2018;7:e009251. 12. Navar AM, Wang TY, Li S, et al. Lipid management in contemporary com munity practice: results from the Provider Assessment of Lipid Management (PALM) Registry. Am Heart J . 2017;193:84–92.

11.3. SGLT-2 Inhibitors and GLP-1 Receptor Agonists

1. Marso SP, Bain SC, Consoli A, et al. Semaglutide and cardiovascular out comes in patients with type 2 diabetes. N Engl J Med . 2016;375:1834– 1844.

2. Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and cardiovas cular outcomes in type 2 diabetes. N Engl J Med . 2016;375:311–322. 3. Neal B, Perkovic V, Mahaffey KW, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med . 2017;377:644–657. 4. Wiviott SD, Raz I, Bonaca MP, et al. Dapagliflozin and cardiovascular out comes in type 2 diabetes. N Engl J Med . 2019;380:347–357. 5. Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular out comes, and mortality in type 2 diabetes. N Engl J Med . 2015;373:2117– 2128. 6. Gerstein HC, Sattar N, Rosenstock J, et al. Cardiovascular and renal out comes with efpeglenatide in type 2 diabetes. N Engl J Med . 2021;385:896– 907. 7. McMurray JJV, Solomon SD, Inzucchi SE, et al. Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med . 2019;381:1995– 2008. 8. Packer M, Anker SD, Butler J, et al. Cardiovascular and renal outcomes with empagliflozin in heart failure. N Engl J Med . 2020;383:1413–1424. 9. Petrie MC, Verma S, Docherty KF, et al. Effect of dapagliflozin on worsening heart failure and cardiovascular death in patients with heart failure with and without diabetes. JAMA . 2020;323:1353–1368. 10. Solomon SD, McMurray JJV, Claggett B, et al. Dapagliflozin in heart fail ure with mildly reduced or preserved ejection fraction. N Engl J Med . 2022;387:1089–1098. 11. Anker SD, Butler J, Filippatos G, et al. Empagliflozin in heart failure with a preserved ejection fraction. N Engl J Med . 2021;385:1451–1461. 12. Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and cardiovascular outcomes in obesity without diabetes. N Engl J Med . 2023;389:2221–2232. 13. American Society of Anesthesiologists Task Force on Preoperative Fast ing. Consensus Based Guidance on Preoperative Management of Patients (Adults and Children) on Glucagon-like Peptide-1 (GLP-1) Receptor Ago nists. Accessed May 9, 2024. https://www.asahq.org/about-asa/newsroom/ news-releases/2023/06/american-society-of-anesthesiologists-consensus-based-guidance-on-preoperative. 14. US Food and Drug Administration. FDA Revises Labels of SGLT2 In hibitors for Diabetes to Include Warnings About Too Much Acid in the Blood and Serious Urinary Tract Infections. Accessed May 9, 2024. https://www.fda.gov/drugs/drug-safety-and-availability/fda-reviseslabels-sglt2-inhibitors-diabetes-include-warnings-about-too-muchacid-blood-and-serious. 15. Thompson A, Fleischmann KE, Smilowitz NR, et al. 2024 AHA/ACC/ ACS/ASNC/HRS/SCA/SCCT/SCMR/SVM guideline for periopera tive cardiovascular management for noncardiac surgery: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation . 2024;150:e351– e442. 16. James S, Erlinge D, Storey RF, et al. Dapagliflozin in myocardial infarction without diabetes or heart failure. NEJM Evid . 2024;3:EVIDoa2300286. 17. Butler J, Jones WS, Udell JA, et al. Empagliflozin after acute myocardial infarction. N Engl J Med . 2024;390:1455–1466.

11.4. Use of Chronic Colchicine

1. Nidorf SM, Eikelboom JW, Budgeon CA, et al. Low-dose colchicine for secondary prevention of cardiovascular disease. J Am Coll Cardiol . 2013;61:404–410. 2. Tardif JC, Kouz S, Waters DD, et al. Efficacy and safety of low-dose colchi cine after myocardial infarction. N Engl J Med . 2019;381:2497–2505. 3. Tong DC, Quinn S, Nasis A, et al. Colchicine in patients with acute coro nary syndrome: the Australian COPS randomized clinical trial. Circulation . 2020;142:1890–1900. 4. Nidorf SM, Fiolet ATL, Mosterd A, et al. Colchicine in patients with chronic coronary disease. N Engl J Med . 2020;383:1838–1847. 5. Fiolet ATL, Opstal TSJ, Mosterd A, et al. Efficacy and safety of low-dose colchicine in patients with coronary disease: a systematic review and metaanalysis of randomized trials. Eur Heart J . 2021;42:2765–2775. 6. Cronstein BN, Molad Y, Reibman J, et al. Colchicine alters the quantitative and qualitative display of selectins on endothelial cells and neutrophils. J Clin Invest . 1995;96:994–1002. 7. Nidorf M, Thompson PL. Effect of colchicine (0.5 mg twice daily) on highsensitivity C-reactive protein independent of aspirin and atorvastatin in patients with stable coronary artery disease. Am J Cardiol . 2007;99:805– 807. 8. Shah $\mathsf{B},$ Allen N, Harchandani $\mathsf{B},$ et al. Effect of colchicine on plateletplatelet and platelet-leukocyte interactions: a pilot study in healthy subjects. Inflammation . 2016;39:182–189. 9. Vaidya K, Arnott C, Martinez GJ, et al. Colchicine therapy and plaque stabili zation in patients with acute coronary syndrome: a CT coronary angiography study. J Am Coll Cardiol Img . 2018;11:305–316. 10. Crittenden DB, Lehmann RA, Schneck L, et al. Colchicine use is associated with decreased prevalence of myocardial infarction in patients with gout. J Rheumatol . 2012;39:1458–1464. 11. Solomon DH, Liu CC, Kuo IH, et al. Effects of colchicine on risk of car diovascular events and mortality among patients with gout: a cohort study using electronic medical records linked with Medicare claims. Ann Rheum Dis . 2016;75:1674–1679. 12. Opstal TSJ, Fiolet ATL, van Broekhoven A, et al. Colchicine in patients with chronic coronary disease in relation to prior acute coronary syndrome. J Am Coll Cardiol . 2021;78:859–866.

11.5. Immunization

1. Frobert O, Gotberg M, Erlinge D, et al. Influenza vaccination after myocardial infarction: a randomized, double-blind, placebo-controlled, multicenter trial. Circulation . 2021;144:1476–1484. 2. Gurfinkel EP, Leon de la Fuente R, Mendiz O, Mautner B. Flu vaccination in acute coronary syndromes and planned percutaneous coronary interven tions (FLUVACS) study. Eur Heart J . 2004;25:25–31. 3. Ciszewski A, Bilinska ZT, Brydak LB, et al. Influenza vaccination in second ary prevention from coronary ischaemic events in coronary artery disease: FLUCAD study. Eur Heart J . 2008;29:1350–1358. 4. Phrommintikul A, Kuanprasert S, Wongcharoen W, et al. Influenza vacci nation reduces cardiovascular events in patients with acute coronary syn drome. Eur Heart J . 2011;32:1730–1735. 5. Madjid M, Miller CC, Zarubaev VV, et al. Influenza epidemics and acute re spiratory disease activity are associated with a surge in autopsy-confirmed coronary heart disease death: results from 8 years of autopsies in 34892 subjects. Eur Heart J . 2007;28:1205–1210. 6. Warren-Gash C, Smeeth L, Hayward AC. Influenza as a trigger for acute myocardial infarction or death from cardiovascular disease: a systematic review. Lancet Infect Dis . 2009;9:601–610. 7. Dvorakova A, Poledne R. Influenza: a trigger for acute myocardial infarction. Atherosclerosis . 2004;172:391. 8. Yedlapati SH, Khan SU, Talluri S, et al. Effects of influenza vaccine on mortality and cardiovascular outcomes in patients with cardiovascular disease: a systematic review and meta-analysis. J Am Heart Assoc . 2021;10:e019636. 9. US Department of Health and Human Services. Centers for Disease Control and Prevention. Recommended adult immunization schedule for ages 19 years or older. Accessed May 1, 2024. https://www.cdc. gov/vaccines/schedules/downloads/adult/adult-combined-schedule. pdf. 10. Gurfinkel EP, de la Fuente RL. Two-year follow-up of the FLU Vaccina tion Acute Coronary Syndromes (FLUVACS) Registry. Tex Heart Inst J . 2004;31:28–32.

Circulation

Appendix 1. Author Relationships With Industry and Other Entities—2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes

| Committee Member |Employment|Consultant| Speakers Bureau | Ownership/ Partnership/ Principal |Personal Research| Institutional, Organizational, or Other Financial Benefit |Expert Witness| |---|---|---|---|---|---|---|---| | Sunil V. Rao, Chair | New York University Langone Health System- Professor of Medicine, Director of Interventional Cardiology | NOT RELEVANT ·Medpace |None|None| NOT RELEVANT NHLBI ·PHRI | NOT RELEVANT ·NHLBI* |None| | Michelle L. O'Donoghue, Vice Chair | Harvard Medical School- Associate Professor, Department of Medicine; Brigham and Women's Hospital-Associate Physician, Senior Investigator, TIMI Study Group, McGillycuddy Logue Distinguished Chair in Cardiovascular Medicine | NOT RELEVANT Verve Therapeutics RELEVANT Amgen ·Novartis |None|None| NOT RELEVANT AstraZeneca/ Medlmmune (DSMB) Janssen Pharmaceuticals (DSMB) RELEVANT Amgent AstraZeneca/ Medlmmunet Merckt Novartist |None|None| | Marc Ruel, Vice Chair | University of Ottawa Heart Institute-Professor, Divi- sion of Cardiac Surgery and Department of Cellular and Molecular Medicine | RELEVANT ·Edwards Lifesciences Medtronic ·XyloCor |None|None| RELEVANT Artivion# Artivion* AstraZeneca* CryoLife* Medtronic# ·Medtronic* ·PhaseBio* |None|None| | John H. Alex- ander | Duke University School of Medicine-Professor of Medicine, Division of Cardiology | NOT RELEVANT ·Akros Antev Artivion AtriCure Curis Ferring Pharmaceu- ticals Humacyte Janssen Pharma- ceuticals Novostia Portolat Teikoku Pharma Veralox RELEVANT Bayer ·Bristol Myers Squibb ·Pfizert |None|None| NOT RELEVANT AbbVie (DSMB) AtriCure (DSMB) Eli Lilly/Duke University (DMC) FDA+ Ferring Pharmaceuticalst GlaxoSmithKline (DSMB) NIH Theravance (DSMB) RELEVANT Artiviont | RELEVANT · Boehringer Ingelheim |None| | John H. Alex- ander | Duke University School of Medicine-Professor of Medicine, Division of Cardiology | NOT RELEVANT ·Akros Antev Artivion AtriCure Curis Ferring Pharmaceu- ticals Humacyte Janssen Pharma- ceuticals Novostia Portolat Teikoku Pharma Veralox RELEVANT Bayer ·Bristol Myers Squibb ·Pfizert ||| Bayer Bristol Myers Squibbt .CSL Behringt | RELEVANT · Boehringer Ingelheim |None| |Usman Baber| University of Oklahoma Health Sciences Center- Associate Professor of Medicine | RELEVANT ·Abbott ·Amgen ·AstraZeneca Boston Scientific |None|None|None| RELEVANT ·Abiomed* .Idorsia Pharma* | NOT RELEVANT Defendant, heart failure after acute MI,2022 Defendant, injury after PCl,2022 | | Heather Baker, Patient Representative | Dorothy Simon Elemen- tary School-Principal; Aurora University-Adjunct Professor |None|None|None|None| NOT RELEVANT ·AHA SFRN# |None| | Mauricio G. Cohen | Cleveland Clinic Florida- Director, Structural Heart Interventions; Staff Physi- cian, Interventional Cardiology, Heart Vascular Center | RELEVANT ·Baylis/Boston Scientific Cordis |None| RELEVANT Accumed Radial Systemst | RELEVANT ·Abbott | NOT RELEVANT ·SCA# ·Abbott* |None| | Mercedes Cruz- Ruiz, Patient Representative | HealthBridge4u-Certified State Community Health Worker, Instructor |None|None|None|None|None|None|

Appendix 1. Continued

| Committee Member |Employment|Consultant| Speakers Bureau | Ownership/ Partnership/ Principal |Personal Research| Institutional, Organizational, or Other Financial Benefit |Expert Witness| |---|---|---|---|---|---|---|---| |Leslie L. Davis| University of North Carolina, Chapel Hill- Associate Professor, PhD Division, Schoo of Nursing |None|None|None| NOT RELEVANT AANP | NOT RELEVANT AANP ACC Elsevier Nursing Clinics of North America PCNA Sigma Theta Tau International Honor Society Skin, Bones, Hearts Private Parts The Journal for Nurse Practitioners |None| | James A. de Lemos | University of Texas Southwestern Medical Center-Professor of Medicine, Chief of Cardiology | NOT RELEVANT ·LianBiot RELEVANT Cytokineticst GlaxoSmithKlinet |None|None| NOT RELEVANT Amgen (DMC) AstraZeneca (DSMB) Beckman Coulter (Endpoint Committee)t Eli Lilly(DSMB)+ Janssen Pharmaceuticals (DSMB)+ Merck (DSMB) Novo Nordisk (DSMB)+ Regeneron (DSMB) Siemens (Endpoint Committee)t Varian Medical Systems (DSMB) Verve Therapeutics (DSMB) RELEVANT Abbottt Roche Diagnosticst |None|None| | Tracy A. Dewald | Duke Heart Center- Clinical Pharmacist and Assistant Consulting Professor, Department of Medicine | NOT RELEVANT Bodyport |Mon|| NOT RELEVANT NHLBI (PI) | NOT RELEVANT Cytokineticst ·Novartis (Co-PI)* |None| | Tracy A. Dewald | Duke Heart Center- Clinical Pharmacist and Assistant Consulting Professor, Department of Medicine | NOT RELEVANT Bodyport |||| NOT RELEVANT Cytokineticst ·Novartis (Co-PI)* |None| |Islam Y. Elgendy| University of Kentucky- Assistant Professor of Medicine |None|None|None|None|None|None| | Dmitriy N. Feldman | Weill Cornell Medical College, New York Presbyterian Hospital- Professor of Medicine |None|None|None|None| RELEVANT ·Medtronic* |None| |Abhinav Goyal| Emory University School of Medicine-Professor of Medicine (Cardiology); Professor of Epidemiology; Emory Rollins School of Public Health-Chief Quality Officer, Emory Heart and Vascular Center, Emory Healthcare |None|None|None|None|None|None| |ljeoma Isiadinso| Emory University School of Medicine-Associate Professor of Medicine; Director of the Emory Center for Heart Disease Prevention |None|None|None|None| NOT RELEVANT 。Abbott (DSMB) AHA ·Eli Lilly* ·Novartis* · University of Florida* |None| |||||||||

Appendix 1. Continued

| Committee Member |Employment|Consultant| Speakers Bureau | Ownership/ Partnership/ Principal |Personal Research| Institutional, Organizational, or Other Financial Benefit |Expert Witness| |---|---|---|---|---|---|---|---| |Venu Menon| Cleveland Clinic Lerner College of Medicine- Professor of Medicine; Mehdi Razavi Endowed Educational Chair; Director of the Cardiac ICU; Direc- tor of the Cardiovascular Fellowship |None|None|None| NOT RELEVANT Edwards Lifesciencesll |None|None| | David A. Morrow | Harvard Medical School- Professor of Medicine; Brigham and Women's Hospital-Section Head, Critical Care Cardiology, Cardiovascular Division | NOT RELEVANT Inflammatix RELEVANT Abbottt ARCA Biopharma Merckt Novartist Regeneront Rochet |None|None| NOT RELEVANT ·InCarda (DSMB) ·Softcellt RELEVANT Abbottt Abiomedt Amgent Anthos Therapeuticst ARCA Biopharmat AstraZenecat Daiichi Sankyot Eisait GlaxoSmithKlinet Johnson Johnsont ·Merckt ·Novartist Pfizert Regeneront Rochet Siemenst |None|None| | Debabrata Mukherjee | Texas Tech University- Professor and Chair, Department of Internal Medicine, Chief, Cardiovascular Medicine | NOT RELEVANT ACC+ |None|None|None| NOT RELEVANT NIH# |None| |Elke Platz| Brigham and Women's Hospital-Assistant Professor of Medicine, Cardiovascular Division; Harvard Medical School- Associate Professor of Emergency Medicine |None|None|None|None| NOT RELEVANT ·AHAt Cambridge University Press CVCT Future Clinic Trialist fellowship European Heart Journal-Acute Cardiovascular Caret European Journal of HeartFailuret ·NIH+ Women As Onet RELEVANT AstraZeneca |None| |Elke Platz| Brigham and Women's Hospital-Assistant Professor of Medicine, Cardiovascular Division; Harvard Medical School- Associate Professor of Emergency Medicine ||||| NOT RELEVANT ·AHAt Cambridge University Press CVCT Future Clinic Trialist fellowship European Heart Journal-Acute Cardiovascular Caret European Journal of HeartFailuret ·NIH+ Women As Onet RELEVANT AstraZeneca |None| | SusanB. Promes | Pennsylvania State University-Professor and Chair, Department of Emergency Medicine |None|None| NOT RELEVANT ·ROMTech |None| NOT RELEVANT ACEP McGraw Hillt Penn State University Department of Emergency Medicinet SAEMt |None| |TanveerRab| Emory University School of Medicine-Professor of Medicine, Interventional Cardiology |None|None|None|None| NOT RELEVANT ABIM ·ACC Medtronic SCAI |None| |Sigrid Sandner| Medical University of Vienna-Associate Professor of Cardiac Surgery |None|None|None|None| NOT RELEVANT Annals of Thoracic Surgery,enior Edi Marizyme, Inc. |None|

Appendix 1. Continued

| Committee Member |Employment|Consultant| Speakers Bureau | Ownership/ Partnership/ Principal |Personal Research| Institutional, Organizational, or Other Financial Benefit |Expert Witness| |---|---|---|---|---|---|---|---| |Yader Sandoval| Minneapolis Heart Insti- tute, Abbott Northwestern Hospital-Interventional Cardiologist; Center for Coronary Artery Disease; Minneapolis Heart Institute Foundation-Investigator | RELEVANT Abbottt GE Healthcare Philipst ·Rochet zo | RELEVANT ·Philipst ·Rochet | NOT RELEVANT ·Patent# | NOT RELEVANT AHRQ (DSMB) .IFCC Committee on Clinical Applications of Cardiac Bio-Markers# NHMRC (CEAC)# | NOT RELEVANT JACC: Advances |None| | Rachel Schunders | AHA/ACC-Science and Health Advisor, Guidelines |None|None|None|None| NOT RELEVANT AHA/ACC salaried employee |None| |Binita Shah| New York University Grossman School of Medi- cine-Associate Professor of Medicine; VA New York Harbor Healthcare System-Interventional Cardiologist | NOT RELEVANT Horizons Therapeutics Terumo Medical RELEVANT ·Boston Scientific Philips Volcanot |None|None| NOT RELEVANT CRF (CEC) Novo Nordiskt The Icahn School of Medicine at Mount Sinai (CEC) | NOT RELEVANT Abiomed * Alleviant* Circulation: Cardiovascular Interventionst Idorsia* PHRI* SCAI# NHLBI VA Office of Research and Development |None| | Jason P.Sto- Pyra | Wake Forest School of Medicine-Professor, Department of Emergency Medicine | NOT RELEVANT Cytovale RELEVANT ·Roche |None|None| NOT RELEVANT AHROt Comprehensive Research Associates, LLC Forest Devices HRSA+ The Duke Endowmentt RELEVANT Abbott Chiesi Genetesis Polymedco |None| NOT RELEVANT Defendant, tendon injury,2022 Plaintiff, pulmonary embolus,2022 Plaintiff, glaucoma, 20:23 Defendant, spinal ssion,2023 | |Amy W. TalbotS| AHA/ACC-Science and Health Advisor, Guidelines ||||None| NOT RELEVANT AHA/ACC salaried employee |None| | Jacqueline E. Tamis-Holland | Cleveland Clinic- Interventional Cardiologist | NOT RELEVANT Gaffney Educa- | NOT RELEVANT || NOTRELEVANT .PHRI | NOT RELEVANT AHA# |None| | Jacqueline E. Tamis-Holland | and Institute Director for Acute Cardiac Care |tional Trust|EBIX#|| Shockwave Medical# | Bronx Lebanon Hos- pitalt Concepts Medical* Encore Medical Education NYS SCAI# Simply K Events |None| |Pam R. Taub| University of California at San Diego-Professor of Medicine; Director of Step Family Foundation Cardiac Rehabilitation and Wel- ness Center | NOT RELEVANT ·Jazz Pharmaceuticalst Lexicon Pharmaceuticals RELEVANT ·Amgen ·Bayert Boehringer Ingelheimt CSL Behring Edwards Lifesciences Eli Lillyand Companyt Esperiont Janssen Pharmaceuticalst Medtronic Novartist Novo Nordiskt Sanofi-Aventis |None| NOT RELEVANT Epirium Biot | NOT RELEVANT Argenxt AtriCuret Dexcom Regeneront RELEVANT ·Merck Novartist | NOT RELEVANT Milestone Pharmaceuticals |None|

Appendix 1. Continued

| Committee Member | Employment|Consultant| Speakers Bureau | Ownership/ Partnership/ Principal |Personal Research| Institutional, Organizational, or Other Financial Benefit |Expert Witness| |---|---|---|---|---|---|---|---| | Marlene S. Wil- liams || NOT RELEVANT|None|None|None||| || Johns Hopkins Bayview Medical Center-Clinical Director of Cardiology and Associate Professor of Medicine |Haemonetics|||| NOT RELEVANT zoll |None|

This table represents all relationships of committee members with industry and other entities that were reported by authors, including those not deemed to be relevant to this document, at the time this document was under development. The table does not necessarily reflect relationships with industry at the time of publication. A person is deemed to have a significant interest in a business if the interest represents ownership of ${\geq}5\%$ of the voting stock or share of the business entity, or ownership of $\tt\ge5000$ of the fair market value of the business entity; or if funds received by the person from the business entity exceed $5\%$ of the person’s gross income for the previ ous year. Relationships that exist with no financial benefit are also included for the purpose of transparency. Relationships in this table are modest unless otherwise noted. Please refer to https://www.acc.org/guidelines/about-guidelines-and-clinical-documents/relationships-with-industry-policy for definitions of disclosure categories or additional information about the ACC/AHA Disclosure Policy for Writing Committees.

\*This disclosure was entered under the Clinical Trial Enroller category in the ACC’s disclosure system. To appear in this category, the author acknowledges that there is no direct or institutional relationship with the trial sponsor as defined in the (ACCF or AHA/ACC) Disclosure Policy for Writing Committees.

†Significant relationship.

‡No financial benefit.

§Rachel Schunder and Amy Talbot are AHA/ACC joint staff members and acted as the Science and Health Advisors for the “2025 ACC/AHA/ACEP/NAEMSP/ SCAI Guideline for the Management of Patients With Acute Coronary Syndromes.” No relevant relationships to report. Nonvoting author on recommendations and not included/counted in the RWI balance for this committee.

‖ The Centers for Medicare & Medicaid Services reported research funding from Edwards Lifesciences to Dr. Menon in 2023 for the ASCEND Study, Commence Pulmonary Study, and the ViV Surveillance Study, which Dr. Menon disputes.

AANP indicates American Association of Nurse Practitioners; ABIM, American Board of Internal Medicine; ACC, American College of Cardiology; ACCF, American College of Cardiology Foundation; ACEP, American College of Emergency Physicians; AHA, American Heart Association; AHRQ, Agency for Healthcare Research and Quality; CEAC, Clinical Events Adjudication Committee; CEC, Clinical Events Committee; CRF, Cardiovascular Research Foundation; CVCT, CardioVascular Clinical Trial ists; DMC, Data Monitoring Committee; DSMB, data and safety monitoring board; HRSA, Health Resources and Services Administration; ICU, intensive care unit; IFCC, International Federation of Clinical Chemistry; JACC , Journal of the American College of Cardiology ; MI, myocardial infarction; NHLBI, National Heart, Lung, and Blood Institute; NAEMSP, National Association of EMS Physicians; NHMRC, National Health and Medical Research Council; NIH, National Institutes of Health; NYS, New York state; PCI, percutaneous coronary intervention; PCNA, Preventive Cardiovascular Nurses Association; PHRI, Population Health Research Institute; PI, principal investiga tor; SAEM, Society for Academic Emergency Medicine; SCAI, Society for Cardiovascular Angiography and Interventions; SFRN, Strategically Focused Research Network; TIMI, Thrombolysis in Myocardial Infarction; and VA, Veterans Affairs.


Circulation

Appendix 2. Reviewer Relationships With Industry and Other Entities—2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes

|Reviewer|Representation|Employment|Consultant| Speakers Bureau | Ownership/ Partnership/ Principal | Personal Research | Institutional, Organizational, or Other Financial Benefit |Expert Witness| |---|---|---|---|---|---|---|---|---| | Hani Jneid, Chair | Official Reviewer- ACC/AHA Joint Committee on Clinical Prac- tice Guidelines | University of Texas Medical Branch-John Sealy Distinguished Centennial Chair in Cardiology; Professor and Chief, Division of Cardiovascular Medicine; Medical Director, Cardiovascular Service Line |None|None|None|None|None|None| | Bruce M.LO | Organizational Reviewer- ACEP | Old Dominion University- Professor/Asstant Program Director; Sentara Norfolk General Hospital-Chief, Depart- ment of Emergency Medicine |None|None|None|None|·AAEM|None| | Frederick wwelt | Organizational Reviewer-SCAl | University of Utah- Director, Cardiac Catheterization Laboratory | ·Faraday Pharma- ceuticals ·Xenter, Inc. |None|None|None|None| Defendant, perforation during angioplasty and stent placement,2024 Defendant, death related to spontaneous bleed, 2024 Defendant, iatrogenic dissection of right coronary artery,2024 | | Craig J. Beavers | Content Reviewer | University of Kentucky-Assistant Adjunct Professor |None|None|None|None|None|None| | Theresa M. Beckie | Content Reviewer | University of South Florida- Professor |None|None|None|None|None|None| | James Blanken- ship | Content Reviewer | University of New Mexico- Professor; University of New Mexico Health Sciences- Director of Cardiac Catheterization Laboratories | ·AMA ·FDA |None|None|None|·ZOLL Medical| None rican | | Deborah Diercks | Content Reviewer | UT Southwestern Medical Center-Professor |Celecort|None|None|None| Abbott Canada Emergencies in Medicine Quidel Corp* Siemens Tosoh Biomedical* |None| | Clauden Louis | Content Reviewer | Winter Haven Hospital-Clinical Associate Physician |None|None|CNone|None|None|None| | Faisal M. Merchant | Content Reviewer | Emory University-Director of Cardiac Electrophysiology |None|None|None|None| Heart Rhythm Society |None| | Noreen T. Nazir | Content Reviewer | University of llinois at Chicago- Assistant Professor of Medicine |None|None|None|None|None|None| |DerekSo| Content Reviewer | University of Ottawa Heart Insti- tute-Cardiologist |None|None|None|None|None|None| | Matthew Tomey | Content Reviewer | Mount Sinai Fuster Heart Hospital-Interventional/ Critical Care Cardiologist |None|None|None|None| McGraw-Hill Companies AHA |None|

This table represents all relationships of reviewers with industry and other entities that were reported at the time of peer review, including those not deemed to be relevant to this document, at the time this document was under review. The table does not necessarily reflect relationships with industry at the time of publication. A person is deemed to have a significant interest in a business if the interest represents ownership of ${\geq}5\%$ of the voting stock or share of the business entity, or ownership of $\tt\ge5000$ of the fair market value of the business entity; or if funds received by the person from the business entity exceed $5\%$ of the person’s gross income for the previous year. Relationships that exist with no financial benefit are also included for the purpose of transparency. Relationships in this table are modest unless otherwise noted. Names are listed in alphabetical order within each category of review. Please refer to https://www.acc.org/guidelines/about-guidelines-and-clinical-documents/ relationships-with-industry-policy for definitions of disclosure categories or additional information about the ACC/AHA Disclosure Policy for Writing Committees.

\*Significant relationship.

†No financial benefit.

AAEM indicates American Academy of Emergency Medicine; ACC, American College of Cardiology; ACEP, American College of Emergency Physicians; AHA, Ameri can Heart Association; AMA, American Medical Association; FDA, US Food and Drug Administration; NAEMSP, National Association of EMS Physicians; SCAI, Society for Cardiovascular Angiography and Interventions; and UT, University of Texas.

相关指南

• 2025 NHFA／CSANZ临床指 南：急性冠脉综合征的诊断和管理 · 心血管内科 2025
• 急性冠状动脉综合征特殊人群抗血小板治疗中国专家建议 · 心血管内科 2018
• 2017 AHA／ACC报告：成人ST抬高和非ST段抬高型心肌梗死的临床表现和质量分层 · 心血管内科 2017
• 稳定性冠心病基层诊疗指南（2020年） · 心血管内科 2020
• 2025 AHA科学声明：老年人冠状动脉血运重建术 · 心血管内科 2025
• 稳定性冠心病基层诊疗指南（2020年） · 心血管内科 2020
• 2024 AHA_ARC指南：急救 · 外科 2024
• 2025 日本临床实践指南：卟啉症的管理（英文版） · 血液内科 2025