2025 NHFA／CSANZ临床指南：急性冠脉综合征的诊断和管理

其他心血管内科· 冠心病与冠脉疾病 · 2025

National Heart Foundation of Australia & Cardiac Society of Australia and New Zealand: Comprehensive Australian Clinical Guideline for Diagnosing and Managing Acute Coronary Syndromes 2025

David Brieger , MBBS, MMed(ClinEpi), PhD a , b , 1 , 2 , Louise Cullen , MBBS, FACEM, PhD c , d , 1 , 2 , Tom Briffa , PhD e , 1 , 2 , Sarah Zaman , MBBS, PhD f , g , 2 , Ian Scott , FRACP, MHA, MEd h , i , 2 , Cynthia Papendick , MBMS, FACEM j , 2 , Kimberley Bardsley , MN(Cardiothoracic), GDip(ClinTeach), MN(NP) k , Angus Baumann , MBBS, BSc l , Alexandra (Sasha) Bennett , BPharm, PhD, FSHP b , m , Robyn A. Clark , BN, PhD, FAAN n , J. James Edelman , PhD, FRACS o , Sally C. Inglis , BN, BHSc, PhD p , Lisa Kuhn , PhD, MHlthSc, RN q , r , Adam Livori , MClinPharm, FANZCAP, FCSANZ s , t , Julie Redfern , PhD, BAppSc(Physio), BSc u , Hans Schneider , MD, FRACP, FRCPA v , w , Jeanine Stewart , BN, GDip(Cardiol), MN(NP) k , x , Liza Thomas , MBBS, PhD f , g , y , z , Edwina Wing-Lun , MBBS aa , Ling Zhang , BNurse, PhD b , Elaine Ho , MHSc(IPH), BSc(NutrDiet) ab , Stacey Matthews , BN, ${\bf M P H}^{\mathrm{ab}}$ , other members of the Heart Foundation Working Group 3 , \*

a Department of Cardiology, Concord Repatriation General Hospital, Sydney, NSW, Australia b Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia c Emergency and Trauma Centre, Royal Brisbane and Woman ’ s Hospital Health Service District, Metro North Health, Herston, Qld, Australia d School of Medicine, Faculty of Health, Queensland University of Technology, Brisbane, Qld, Australia e School of Population and Global Health, The University of Western Australia, Nedlands, WA, Australia f Department of Cardiology, Westmead Hospital, Westmead, NSW, Australia g Westmead Applied Research Centre, The University of Sydney, Sydney, NSW, Australia h Metro South Digital Health and Informatics, Qld, Australia i Centre for Health Services Research, The University of Queensland, Brisbane, Qld, Australia j Department of Emergency Medicine, The Royal Adelaide Hospital, Adelaide, SA, Australia k The Prince Charles Hospital, Brisbane, Qld, Australia l Department of Cardio-respiratory Medicine, Alice Springs Hospital, The Gap, NT, Australia m NSW Therapeutic Advisory Group, Sydney, NSW, Australia n Caring Futures Institute, Flinders University, Bedford Park, SA, Australia o Department of Cardiothoracic Surgery and Transplantation, Fiona Stanley Hospital, The University of Western Australia, Perth, WA, Australia p Improving Palliative, Aged and Chronic Care through Clinical Research and Translation (IMPACCT), Faculty of Health, University of Technology Sydney, Sydney, NSW, Australia q School of Nursing, Midwifery and Paramedicine, Australian Catholic University, Fitzroy, Vic, Australia r Monash Emergency Research Collaborative, Monash Health, Clayton, Vic, Australia s Grampians Health, Ballarat, Vic, Australia t Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Melbourne, Vic, Australia u Institute for Evidence-Based Healthcare, Bond University, Gold Coast, Qld, Australia v Department of Pathology, Alfred Health, Melbourne, Vic, Australia w School of Public Health and Preventative Medicine, Monash University, Melbourne, Vic, Australia x School of Nursing and Midwifery, Grif ﬁ th University, Qld, Australia y Westmead Clinical School, The University of Sydney, Sydney, NSW, Australia z South West Sydney School of Clinical Medicine, University of New South Wales, Sydney, NSW, Australia aa Department of Cardiology, Royal Darwin Hospital, Darwin, NT, Australia ab National Heart Foundation of Australia

Received 17 February 2025; accepted 17 February 2025

Summary of Recommendations............................................................................................................................................................ 313 Introduction ............................................................................................................................................................................................. 319 Purpose ..................................................................................................................................................................................................... 319 Scope ......................................................................................................................................................................................................... 320 Intended Audience.................................................................................................................................................................................. 320 What ’ s New in this Guideline?............................................................................................................................................................. 320 The Guideline Update Process.............................................................................................................................................................. 321 Development of Recommendations and Using this Guideline ....................................................................................................... 321 Con ﬂ icts of Interest................................................................................................................................................................................. 322 1. Preamble............................................................................................................................................................................................... 323 1.1. Impact of ACS in Australia ...................................................................................................................................................... 323 1.2. De ﬁ nitions and Terminology.................................................................................................................................................... 323 1.2.1. Fourth universal de ﬁ nition of myocardial infarction............................................................................................ 323 1.2.2. Revised de ﬁ nition of myocardial infarction ........................................................................................................... 323 1.2.3. De ﬁ nition of major adverse cardiovascular events............................................................................................... 324 1.2.4. De ﬁ nition of unstable angina.................................................................................................................................... 324 1.2.5. Myocardial infarction with non-obstructive coronary arteries............................................................................ 324 1.3. Shared Decision Making ........................................................................................................................................................... 325 1.4. Collaborative Approaches to Care for First Nations Peoples............................................................................................. 325 2. Assessment and Diagnosis................................................................................................................................................................ 326 2.1. Assessment of People with Suspected ACS........................................................................................................................... 326 2.1.1. Initial assessment summary ...................................................................................................................................... 326 2.1.2. History of the presenting complaint........................................................................................................................ 327 2.2. Initial ECG Assessment............................................................................................................................................................. 329 2.2.1. ECG ﬁ ndings of acute coronary occlusion myocardial infarction...................................................................... 329 2.2.2. High-risk ECG ﬁ ndings ............................................................................................................................................. 331 2.2.3. Other signs of myocardial ischaemia on ECG ....................................................................................................... 331 2.2.4. Continuous ECG monitoring .................................................................................................................................... 332 2.2.5. Future direction........................................................................................................................................................... 333 2.3. Biomarkers................................................................................................................................................................................... 333 2.3.1. Analytic properties of cardiac troponin assays...................................................................................................... 333 2.3.2. Point-of-care troponin assays.................................................................................................................................... 334 2.3.3. Clinical interpretation of troponin values............................................................................................................... 334 2.3.4. Time from onset of coronary occlusion vs. symptom onset................................................................................ 335 2.3.5. Comparing results from different troponin assays ............................................................................................... 335 2.4. Risk Assessment and Clinical Decision Pathways for Suspected ACS............................................................................. 337 2.4.1. Clinical decision pathways........................................................................................................................................ 337 2.4.1.1. High-sensitivity troponin-based clinical decision pathways .................................................................. 338 2.4.1.2. Clinical score-based clinical decision pathways....................................................................................... 339 2.4.2. Implementing a clinical decision pathway for suspected ACS........................................................................... 339 2.4.3. Future direction........................................................................................................................................................... 341 2.5. Initial Therapeutic Management.............................................................................................................................................. 341 2.6. Further Diagnostic Testing for People with Suspected ACS .............................................................................................. 342 2.6.1. Cost-effectiveness ........................................................................................................................................................ 345 2.6.2. Considerations for regional, remote and First Nations peoples ......................................................................... 345 2.7. Role of Rapid Access Chest Pain Clinics................................................................................................................................ 345 2.8. Re-presentation with Symptoms.............................................................................................................................................. 345 2.9. Discharge Planning and Advice .............................................................................................................................................. 345 2.9.1. Discharge communication for general practitioners ............................................................................................. 345 2.9.2. Discharge advice for people at low risk for ACS.................................................................................................. 345 2.9.3. Discharge advice for people at intermediate risk for ACS .................................................................................. 346 2.9.4. Discharge advice for people with a prior history of coronary heart disease who have a chronic or stable 346 coronary syndrome..................................................................................................................................................... 2.10. Primary Care and Regional and Remote Presentations..................................................................................................... 346 2.10.1. Considerations for primary care presentation...................................................................................................... 346 2.10.2. Considerations for regional and remote presentations....................................................................................... 347 3. Hospital Care and Reperfusion........................................................................................................................................................ 348 3.1. Acute Management of STEMI – Reperfusion for STEMI .................................................................................................... 348 3.1.1. Eligibility for reperfusion........................................................................................................................................... 348 3.1.2. Choice of reperfusion strategy.................................................................................................................................. 348 3.1.3. Administration of ﬁ brinolytic therapy .................................................................................................................... 349 3.1.4. Procedural recommendations in primary percutaneous coronary intervention............................................... 351 3.2. Ongoing Management of Fibrinolytic-Treated People......................................................................................................... 352 3.3. Acute Management of NSTEACS............................................................................................................................................ 353 3.3.1. Risk strati ﬁ cation for people with con ﬁ rmed NSTEACS..................................................................................... 353 3.3.2. Routine versus selective invasive management for NSTEACS........................................................................... 355 3.3.3. Timing of invasive management for NSTEACS .................................................................................................... 355 3.3.4. Procedural considerations in NSTEACS ................................................................................................................. 357 3.4. Antiplatelet Therapy in the Acute Phase ............................................................................................................................... 358 3.5. Anticoagulant Therapy in the Acute Phase ........................................................................................................................... 361 3.6. Acute Management of ACS with Cardiac Arrest and/or Cardiogenic Shock................................................................. 362 3.6.1. ACS with cardiac arrest............................................................................................................................................. 362 3.6.2. ACS with cardiogenic shock ..................................................................................................................................... 362 3.7. Treatment for ACS with Multivessel Disease without Cardiogenic Shock...................................................................... 364 3.8. Coronary Artery Bypass Graft Surgery in ACS.................................................................................................................... 365 3.9. Treatment for Spontaneous Coronary Artery Dissection .................................................................................................... 366 3.10. Myocardial Infarction with Non-Obstructive Coronary Arteries..................................................................................... 366 3.11. Myocardial Infarction due to Oxygen Supply/Demand Mismatch without Acute Coronary Occlusion................. 366 3.12. Echocardiography..................................................................................................................................................................... 366 3.13. Duration of Cardiac Monitoring............................................................................................................................................ 367 4. Recovery and Secondary Prevention............................................................................................................................................... 368 4.1. Person-Centred Non-Pharmacological Secondary Prevention............................................................................................ 368 4.2. Vaccination Against In ﬂ uenza and Other Respiratory Pathogens..................................................................................... 370 4.3. Post-ACS Pharmacotherapy...................................................................................................................................................... 370 4.3.1. Antiplatelet therapy.................................................................................................................................................... 370 4.3.2. Lipid-modifying therapy............................................................................................................................................ 374 4.3.3. Beta blocker therapy................................................................................................................................................... 375 4.3.4. Renin-angiotensin antagonist therapies................................................................................................................... 376 4.3.5. Colchicine therapy ...................................................................................................................................................... 377 Acknowledgements................................................................................................................................................................................. 377 Funding..................................................................................................................................................................................................... 377 Endorsements .......................................................................................................................................................................................... 377 Appendices............................................................................................................................................................................................... 377 References................................................................................................................................................................................................. 383

## Acknowledgement of Country

We acknowledge the Traditional Owners and custodians of country throughout Australia and their continuing connection to land, waters and community. We pay our respects to them and their cultures, and Elders past, present and future.

First Nations peoples is the term used throughout this guideline. However, the Heart Foundation recognises that the preferred term(s) when writing for, and about, First Nations peoples can differ between communities and individuals. No disrespect is intended to First Nations peoples who may identify with an alternative term.

Disclaimer

This guideline has been developed by the National Heart Foundation of Australia ABN 98 008 419 761 ( Heart Foundation ) in collaboration with the Cardiac Society of Australia and New Zealand ABN 23 006 63505 ( CSANZ ) to support healthcare professionals in making informed clinical decisions. The content of this guideline is general advice only and provided for informational purposes only. It is not intended to serve as health, medical, or treatment advice. It is based on the best available evidence and expert consensus as at the time of publication. The recommendations are intended to support, not replace, the clinical judgment and shared decision-making process between quali ﬁ ed healthcare professionals and the people they care for, considering an individual ’ s circumstances and the availability of resources.

Intended use

This guideline is expressly intended for use by appropriately quali ﬁ ed healthcare professionals within Australia. It is intended as a reference tool and is not designed for use by individuals without proper medical training except under the supervision of a quali ﬁ ed healthcare professional. Any reliance on the content by unquali ﬁ ed individuals is at their own risk. The Heart Foundation does not warrant that the content in this guideline is suitable for your needs or any speci ﬁ c purpose. Users are responsible for assessing whether the information is accurate, reliable, up-to-date, authentic, relevant, or complete, and where appropriate, should seek independent professional advice.

Liability limitation

The Heart Foundation, including its employees, of ﬁ cers, collaborators, and associated institutions, disclaims and excludes, to the maximum extent permitted by law, all responsibility and liability (including liability in negligence) for any direct, special, indirect, incidental, consequential, punitive, exemplary, or other loss, damage, cost, or expense arising out of, or in connection with, the use or reliance on this guideline or any information contained within it, including any inaccuracies or omissions. This guideline is not exhaustive and may not apply to all clinical situations.

## Third-party references

Any reference to third-party organisations, products, or services within this guideline does not constitute an endorsement or recommendation by the Heart Foundation. The inclusion of such references is for informational purposes only, and the Heart Foundation is not responsible for the content, accuracy, or actions taken based on information from external sources.

## Copyright and permissions

This material is protected by copyright, and any reproduction, distribution, or use of this guideline requires prior written permission from the Heart Foundation. For permissions or enquiries, please contact copyright@heartfoundation.org.au .

## Clinical judgment and decision making

This guideline should not override the responsibility of healthcare professionals to make appropriate decisions based on the speci ﬁ c circumstances of each person, including consideration of applicable local regulations and the person ’ s values and preferences. Healthcare professionals are also responsible for verifying current regulations and recommendations before applying any treatments or interventions referred to in this guideline.

## Updates and revisions

Medical knowledge is continually evolving, and guidelines may be updated as new information becomes available. Users are encouraged to consult the latest version of the guideline and to consider any new evidence that may have emerged.

## Jurisdictional application

This guideline has been developed in accordance with Australian regulatory and clinical standards and may not be suitable for use in other jurisdictions without appropriate adaptation.

## Summary of Recommendations

|Recommendation| Strength of recommendation ||| |---|---|---|---| |ASSESSMENT AND DIAGNOSIS|||| ||||| | In people presenting with chest pain or other symptoms suggestive of ACS, record and assess an|||| |ECG for evidence of ACOMI within 10 minutes of first clinical contact.|| Consensus|| ||||| | In people with suspected ACS, record and assess additional ECGs if symptoms persist, change, or|| Consensus|| |inconclusive standard 12-lead ECG, record and assess further ECGs with right-sided and/or |||| | posterior leads.|||| | In people with ongoing ischaemic symptoms or haemodynamic compromise or new ischaemic|||| |findings on ECG, continuous cardiac monitoring and defibrillator availability is recommended|Strong|LOw|| |while assessment for ACOMI continues.|||| || Biomarkers||| | In people with suspected ACS, evaluation with high-sensitivity cardiac troponin (hs-cTn) assays is recommended. |Strong|High|| | percentiles. Consensus|||| | Apply the assay-specific troponin values relevant to the cTn assay being used.|| Consensus|| | When evaluating changes (deltas) in troponin values, serial results from a single assay must be used.|| Consensus|| ||||| | Risk assessment and clinical decision pathways for suspected ACS People with symptoms and ECG changes consistent with ACOMI require urgent reperfusion. |Strong||| |||Very Low|| | People presenting with acute chest pain or other symptoms suggestive of ACS should receive care || Consensus|| |guided by an evidence-based CDP that includes asay-specific troponin results to categorise people|||| | as high, intermediate, or low risk. |||| | A high-sensitivity troponin-based clinical decision pathway is recommended, using the 0/1-hour or || Consensus|| |0/2-hour strategy, or the High-sensitioity troponin in the eoaluation of patients with acute coronary|||| | syndrome (High-STEACS) algorithm.|||| ||||| | Consensus stratification is recommended. |||| | In all people with suspected or confirmed ACS, give aspirin (300 mg orally, dissolved or chewed)|Strong|High|| |unless contraindicated.|||| | People with suspected or confirmed ACS with oxygen saturation (SpO2) ≥90% do not require Oxygen therapy. |Strong| Moderate|| |In people with suspected or confirmed ACS receiving oxygen therapy, SpO2 should not exceed 96%.|Strong|Moderate|| |In the presence of ongoing chest pain, give glyceryl trinitrate sublingual tablet or spray every|||| ||| Consensus|| | In people with chest pain and in the absence of contraindications, it is reasonable to administer|||| | intravenous (IV) fentanyl or morphine boluses.| Consensus|||

(continued).

|Recommendation| Strength of recommendation || Certainty of evidence | |---|---|---|---| ||||| | In people at intermediate risk (as defined by a validated CDP) with elevated troponin |Strong| Moderate|| | concentrations (>99th percentile), inpatient investigation is recommended. |||| | In people at intermediate risk without elevated troponin concentrations, consider outpatient investigation with non-invasive testing. || Consensus|| | In people at low risk who remain symptom-free, further cardiac testing for CAD is not routinely required. |||| ||| Consensus|| | Primary care and regional and remote presentations For people with suspected ACS initially evaluated in the primary care setting, prompt transfer to a facility where definitive risk assessment can occur (e.g. ED) is recommended. |||| |||Consensus|| | Metropolitan health services should establish centralised support systems for regional and remote health services to facilitate: ||LOW|| | health services to facilitate: ● prompt assistance with ECG interpretation and accessto troponin results when on-site access is ||Strong|| | ● prompt assistance with ECG interpretation and accessto troponin results when on-site access is not available; |||| |· provision of clinical advice to healthcare professonals;|||| |● access to cardiac investigations if required.|||| |HOSPITAL CARE AND REPERFUSION| Acute management of STEMI Eligibility for reperfusion ||| ||||| | In people with STEMI within 12 hours of symptom onset, perform emergency reperfusion with either primary PCI or fbrinolytic therapy. ||Strong|Moderate| | In people with STEMI, symptom onset over 12 hours before presentation and evidence of||Strong| Moderate| | continuing myocardial ischaemia (persistent ischaemic symptoms, haemodynamic compromise, and/or li-threatening arrhythmias) perform emergency reperfusion with primary PCI |||| || Choice of reperfusion strategy||| | In people with STEMI within 12 hours of symptom onset, primary PCI is the preferred reperfusion strategy over fibrinolysis, if it can be performed within 120 minutes of first medical contact. ||Strong|High| | In people with STEMI within 12 hours of symptom onset, perform fibrinolysis if primary PCI cannot|||| | be delivered within 120 minutes of first medical contact.||Strong|Moderate| ||Administration of fibrinolytic therapy||| || In people with STEMI for whom fibrinolysis is the preferred reperfusion strategy, it should be Strong|| Moderate| |delivered within 30 minutes of first medical contact. Consider pre-hospital administration.|||| | In people aged ≥70 years, half the standard dose of tenecteplase is recommended as part of a pharmaco-invasive strategy. ||Strong| Moderate| ||||| | Procedural recommendations in primary percutaneous coronary intervention For people with STEMI at a PCI-capable centre, deliver primary PCI within 60 minutes of arrival. |||| | For people with STEMI transferred from a non-PCI centre, deliver primary PCI within 90 minutes of first hospital arrival. || Consensus|| ||||| |Use radial access over femoral access when performing primary PCI, unless contraindicated.||Strong.|High| | In people undergoing primary PCI, do not perform routine thrombus aspiration of the infarct- related artery (IRA). |Strong|| Moderate| | In people who are asymptomatic and stable for more than 48 hours following occlusion of an IRA, Strong|||| |||| Moderate| | do not perform routine PCI to this artery.||||

(continued).

| Recommendation| Strength of recommendation | Certainty of evidence || |---|---|---|---| |Ongoing management of fibrinolytic-treated people|||| | People successfully treated with fibrinolytic therapy should be transferred to a PCI-capable centre as|Strong|Moderate|| | soon as possible. Angiography should be performed within 2-24 hours of arrival. Consider transferring people as soon as possible to a PCI-capable centre if fibrinolytic therapy is |||| ||Weak||Moderate| |Acute management of NSTEACS|||| ||||| | In people with NSTEACS, consider using the GRACE risk score to determine short- and long-term|Weak||High| | cardiovascular prognosis.||Moderate|| | In people with ACS undergoing coronary angiography, consider using bleeding risk scores to Weak determine short-term bleeding risk. |||| | Routine versus selective invasive management for NSTEACS|||| | In people with NSTEACS at high or very high-risk of adverse cardiovascular events, perform|Strong||High| | routine invasive coronary angiography, with coronary revascularisation (PCI or CABG) where appropriate. |||| | In people with NSTEACS not at high or very high risk of adverse cardiovascular events, testing for Weak Moderate inducible ischaemia (e.g. stress testing) may guide the need for invasive coronary angiography. |||| ||Timing of invasive management for NSTEACS||| | In people with NSTEACS with very high-risk criteria, an immediate invasive strategy within 2 hours of diagnosis is recommended. || Consensus|| ||||| | In people with NSTEACS with high-risk criteria, consider an early invasive strategy within 24 hours|Weak|High|| || Procedural considerations in NSTEACS||| | In people with NSTEACS undergoing an invasive approach, radial access is preferred to femoral|Strong|High|| | access, unless contraindicated.|||| | In people with NSTEACS undergoing an invasive approach, consider intravascular imaging to guide PCI. |Weak|High|| ||||| | In people with STEMI treated with fibrinolytic therapy, give dual antiplatelet therapy with aspirin and clopidogrel. |Strong| Moderate|| ||||| | In people with STEMI undergoing primary PCI and people with NSTEACS undergoing a routine invasive strategy, give dual antiplatelet therapy with aspirin and a potent P2Y2 inhibitor ticagrelor |Strong|High|| | or prasugrel).|||| |In people with STEMI undergoing primary PCI and people with NSTEACS undergoing a routine|Strong|High|| | invasive strategy for whom ticagrelor or prasugrel are contraindicated, and those receiving oral anticoagulation, give clopidogrel. |||| ||||| | In people with NSTEACS for whom a selective invasive strategy is planned, give ticagrelor or clopidogrel. |Strong|High|| | In people with NSTEACS, consider routine genotypic or platelet function guidance of P2Y12 therapy. |Weak|Moderate|| ||||| | In people with NSTEACS, consider de-escalation from potent P2Y12 inhibitor to clopidogrel, but not Weak Moderate|||| | during the first 30 days following an ACS event.||||

|(continued).|||| |---|---|---|---| | Recommendation | Strength of recommendation | Certainty of evidence || | In people with ACS with concomitant non-valvular atrial fibrillation and CHA2DS2VA score >1,|Strong|High|| | give aspirin and clopidogrel, together with a non-vitamin K oral anticoagulant.|||| | In people with STEMI undergoing primary PCI or those with NSTEACS undergoing an invasive||Consensus|| |strategy, routine glycoprotein Ila/ inhibitor (GPI) is not recommended.|||| | People treated with fibrinolytic therapy should receive anticoagulation (unfractionated heparin or||Strong|Moderate| ||||| | People undergoing primary PCI should receive anticoagulation (unfractionated heparin or bivalirudin). ||Strong|Moderate| ||||| | People with NSTEACS should receive anticoagulation (unfractionated heparin, enoxaparin, or|Strong||LOW| ||Acute management of ACS with cardiac arrest||| | In people with return of spontaneous circulation after resuscitated cardiac arrest and persistent STE on ECG, perform emergency reperfusion. |Strong||LOW| ||Strong|| Moderate| | In haemodynamically stable people with resuscitated cardiac arrest and no STE on ECG, do not perform routine emergency coronary angiography. |||| | In people with ACS and cardiogenic shock, perform PCI of the IRA only.|Acute management of ACS with cardiogenic shock|Strong.|Moderate| | In people with ACS and cardiogenic shock, routine insertion of an intra-aortic balloon pump is not|||High| |recommended.||Strong|| | In people with ACS and cardiogenic shock, routine venoarterial extracorporeal membrane ||Strong|Moderate| | In select people with STEMI and cardiogenic shock, consider left ventricular assist devices.||Weak|Moderate| | Treatment for ACS with multivessel disease without cardiogenic shock |||| | In haemodynamically stable people with STEMI and MVD, perform PCI of suitable non-IRA(s).||.Strong.|High| |||Weak| Moderate| ||||| | In people with STEMI and MVD, routine invasive physiology assessment (e.g. fractional flow|| Consensus|| | In people with NSTEACS and non-complex MVD, consider routine PCI of non-IRA in the same .setting. |Weak|LOW|| | In people with NSTEACS and MVD, consider invasive physiology assessment (e.g. FFR) to evaluate non-IRA severity. |Weak|LOW|| ||||| | In people with STEMI, mechanical complications and mitral valve disease (e.g. ventricular septal | Coronary artery bypass graft surgery in ACS||| | rupture, mitral valve insufficiency because of papillary muscle infarction or rupture, or free wall rupture), perform CABG at the time of surgery. |Strong|LOW|| ||||| | Treatment for spontaneous coronary artery dissection In people with ACOMI due to SCAD but who are otherwise stable, routine revascularisation is not || Consensus|| | recommended.|||| | In people with SCAD and haemodynamic instability and/or ongoing ischaemia, consider selective weak VeryLow|||| | revascularisation.||||

|(continued).|||| |---|---|---|---| |Recommendation| Strength of recommendation | Certainty of evidence || | RECOVERY AND SECONDARY PREVENTION Person-centred non-pharmacological secondary prevention |||| | For all people with ACS, refer to a multi-disciplinary exercise-based cardiac rehabilitation program prior to discharge. |Strong| Moderate|| ||||| | For all people with ACS, provide advice on lifestyle* changes such as healthy eating, regular|| Consensus|| |physical activity, not smoking, limiting alcohol intake, and caring for mental health.|||| | For all people with ACS who smoke, advise to stop and refer for behavioural intervention (such as Strong|||Moderate| | cognitive behaviour therapy or cessation counselling program), combined with pharmacotherapy|||| | where appropriate (nicotine replacement therapies, varenicline and bupropion individually or in combination). |||| | |||| | For all people with ACS, implement strategies to optimise adherence to preventive medicines. For all people with ACS, implement strategies to optimise adherence to preventive medicines. Consensus Vaccination against influenza and other respiratory pathogens |||| |In people with CS, vaccinations forinfuenza and other respiratory pathogens are recommended.|| Consensus|| ||||| | Post-ACS pharmacotherapy Antiplatelet therapy |Strong||| | In people discharged following an ACS who are at high ischaemic and/or low bleeding risk, prescribe DAPT with aspirin and a P2Y12 inhibitor for 6-12 months. ||High|| | In people discharged following an ACS who are at low ischaemic and/or high bleeding risk, cease|Strong|High|| | DAPT at 1-3 months post-ACS and continue single antiplatelet therapy (SAPT).|||| | In people discharged following an ACS who have completed a course of DAPT (i.e. 1-12 months),. Strong||Moderate|| ||||| | In people discharged following an ACS who remain at high ischaemic and low bleeding risk, consider long-term DAPT (>12 months). |Weak| Moderate|| ||||| | In people discharged following an ACS with an indication for long-term OAC therapy, continue|Strong|High|| | OAC and DAPT (preferentially aspirin and clopidogrel) for 1-4 weeks, then cease aspirin.|||| | In people discharged following an ACS with an indication for long-term OAC therapy, cease|Strong| Moderate|| | antiplatelet therapy at 6-12 months and continue anticoagulation alone.|||| ||Lipid-modifying therapy||| | In people with ACS, prior to hospital discharge, initiate and continue indefinitely, the highest |Strong|High || | tolerated dose of HMG-CoA reductase inhibitors (statins), unless contraindicated or completely statin intolerant. |||| | In people with ACS with initial or partial intolerance to statin, consider using a different statin, dose |Weak||| | or dosing frequency to achieve person-specific therapeutic objectives.||LOW|| | In people with ACS, an initial target low density lipoprotein cholesterol (LDL-C) level of|| Consensus|| |||||

|(continued).||||| |---|---|---|---|---| |Recommendation| Strength of recommendation || Certainty of evidence || | In people with ACS with a suboptimal LDL-C level despite maximally tolerated statin therapy and ezetimibe, give PCSK9 inhibitors. || Strong|High|| |||||| |Beta blocker therapy|Beta blocker therapy|||| | In people with ACS and LV impairment, beta blockers are recommended.|| Consensus| Consensus|| | In people with ACS and preserved LV systolic function who have undergone coronary||| Moderate|| | revascularisation and are receiving optimal medical therapy, consider withholding beta blockers.||||| | Renin-angiotensin antagonist therapies|Strong|High||| | chronic kidney disease, initiate and continue angiotensin converting enzyme (ACE) inhibitors, or ||||| |||||| | In people with ACS and LVEF |||||

Introduction

This guideline has been developed to assist in the diagnosis and management of people presenting with symptoms suggestive of acute coronary syndromes (ACS), or with con ﬁ rmed ACS. ACS are conditions involving sudden reduced blood ﬂ ow to the heart. The main types are acute myocardial infarction (AMI) and unstable angina.

The guideline recommendations are based on contemporary evidence and are intended to meet the needs of clinicians caring for the majority of people, recognising that recommendations should inform, but not replace, clinical judgement.

Shared decision making is recommended and should be based on the person ’ s values, preferences and circumstances. Clear communication with the person and their support people is critical to these discussions.

This guideline was developed in consultation with a broad range of clinical experts and people with lived experience,

representing different geographic regions, sex, genders, ethnicities, clinical settings and perspectives. Organisations, including those with people with lived experience interests and professional expertise, were involved.

Purpose

This guideline replaces the National Heart Foundation of Australia & Cardiac Society of Australia and New Zealand: Australian Clinical Guidelines for the Management of Acute Coronary Syndromes 2016 .

The guideline includes:

' recommendations for assessing and managing people with suspected or con ﬁ rmed ACS ' a summary of the available evidence supporting the recommendations ' practical advice on how to apply the recommendations ' speci ﬁ c practice points for assessing and managing ACS in underserved populations.

![Acute coronary syndromes Unstable angina Acutemyocardialinfarction(AMl) STEACS\* NSTEACS (ST-segmentelevationacute (Non-ST-segmentelevation acutecoronary syndromes) coronary syndromes) NSTEMI STEMI Unstable angina (Non-ST-segmentelevation myocardial infarction) (ST-segmentelevationmyocardialinfarction) ACOMI# (AMI due to significant epicardial coronary occlusion) AMI duetoacutecoronaryocclusion ·Plaquerupture/erosionwiththrombus ·SCAD ·Coronary embolism ·Vasospasm or microvascular dysfunction AMI due to oxygen supply/demand mismatchwithout acute coronaryocclusion Non-elevatedtroponin Increasing troponin ](https://venus-trag-1258344701.cos-internal.ap-guangzhou.tencentcos.cn/userUpload/is-62e36cd9/2025-04-10/b6247b99-efcd-4611-af34-3ef787267806/b6247b99-efcd-4611-af34-3ef787267806.jpg?q-sign-algorithm=sha1&q-ak=AKID61g5D5fy1TjiRv84nEOHtFJ8gyzjCPL0&q-sign-time=1744240805%3B1744244405&q-key-time=1744240805%3B1744244405&q-header-list=host&q-url-param-list=&q-signature=ea77992f77346ae241d48bdb75d38efcc6e137f8) Figure 1 Classi ﬁ cations of conditions associated with ACS. Abbreviations: ACOMI, acute coronary occlusion myocardial infarction; $\mathrm{ACS},$ acute coronary syndromes; AMI, acute myocardial infarction; NSTEACS, non-ST-segment elevation acute coronary syndromes; NSTEMI, non-ST-segment elevation myocardial infarction; SCAD, spontaneous coronary artery dissection; STEACS, ST-segment elevation acute coronary syndromes; STEMI, ST-segment elevation myocardial infarction. \*Not all people with ST-segment elevation will have elevated cardiac troponin values, resulting in the diagnosis of unstable angina. # The term ACOMI incorporates both STEMI and STEMI equivalents which should prompt consideration for emergency reperfusion (see section 3.1 Acute Management of STEMI – Reperfusion for STEMI ). Note: Coronary occlusion describes any local pathologic process that reduces ﬂ ow in coronary vessels (including the microvasculature) suf ﬁ cient to cause myocardial necrosis (acute troponin elevation).

Scope

This guideline makes recommendations for:

' assessing adults aged 18 years and older with suspected ACS ' managing con ﬁ rmed ACS ' recovery after ACS and secondary prevention of future vascular events.

The de ﬁ nition of myocardial infarction (MI) has been re ﬁ ned from the Fourth universal de ﬁ nition of myocardial infarction to align more closely with the clinical syndromes that characterise occlusive and non-occlusive MI. This guideline adopts the term acute coronary occlusion myocardial infarction which includes both atherosclerotic and non-atherosclerotic causes.

The guideline predominantly focuses on managing people with MI due to atherosclerotic plaque rupture, ulceration, ﬁ ssure, or erosion. Some recommendations presented in this guideline may be relevant to other types of MI (e.g. type 2 MI), particularly with respect to initial acute treatment and post-hospital care. Speci ﬁ c recommendations are presented in some cases for MI due to non-atherosclerotic causes (e.g. spontaneous coronary artery dissection [SCAD]) ( Figure 1 ).

The guideline does not cover management of non-ACS presentations and non-cardiac chest pain. It does not include detailed guidance on managing related clinical conditions, such as heart failure, or comorbidities such as cancer or diabetes. Healthcare professionals should refer to existing guidance, where available.

Intended Audience

This guideline is intended for use by all healthcare professionals involved in the care of people with ACS. These include cardiologists, emergency physicians, general practitioners, nurses and nurse practitioners, First Nations health workers and practitioners, pharmacists and other allied healthcare professionals.

General practitioner is the term used throughout this guideline. However, the Heart Foundation recognises other primary healthcare professionals, who in some communities may be the ﬁ rst point of contact with the health system. Other primary healthcare professionals include primary care nurses and nurse practitioners, and First Nations health workers and practitioners.

What ’ s New in this Guideline?

Key changes in this guideline

' Introduction of consensus recommendation as a new category of recommendation. ' Dedicated practice points to meet the unique needs of women, older adults, First Nations peoples, and people living in regional and remote areas. ' Revised terminology and de ﬁ nitions of myocardial infarction (section 1.2).

Assessment and diagnosis

' Guidance on assessing and interpreting the electrocardiogram in people with suspected acute coronary occlusion myocardial infarction or myocardial ischaemia (section 2.2). ' Guidance on using high-sensitivity cardiac troponin testing and interpreting the results to enable more rapid detection or exclusion of myocardial injury (section 2.3). ' Introduction of high-sensitivity troponin-based clinical decision pathways to stratify risk in people with suspected ACS (section 2.4). ' Recommendations to support management of people with suspected ACS presenting to primary care and regional and remote settings (section 2.10).

Hospital care and reperfusion

' Updates on recommended timing of reperfusion strategies in people with ST-segment elevation myocardial infarction (section 3.1). ' Consideration of intravascular imaging to guide percutaneous coronary intervention in people with non-ST-segment elevation ACS who have undergone an invasive approach (section 3.3.4). ' Revised recommendations on acute phase pharmacotherapies (sections 3.4 and 3.5). ' New recommendations related to haemodynamic support devices in people with ACS and cardiogenic shock (section 3.6.2). ' Treatment considerations for people with ACS and multivessel disease without cardiogenic shock (section 3.7) and spontaneous coronary artery dissection (section 3.9).

(continued).

Recovery and secondary prevention

' New recommendations and practice points on delivery of person-centred, non-pharmacological secondary prevention care (section 4.1). ' Guidance on recommended vaccinations for people with ACS (section 4.2). ' Updates on duration of dual antiplatelet therapy and indications for long-term oral anticoagulation (section 4.3.1). ' New recommendations on low-density lipoprotein cholesterol (LDL-C) treatment targets and post-ACS lipidmodifying therapy, including non-statin therapies (section 4.3.2). ' Considerations for withholding beta blockers in select people with ACS with preserved left ventricular systolic function (section 4.3.3). ' New recommendations on the use and non-use of reninangiotensin antagonist therapies (section 4.3.4) and on initiating colchicine post-ACS (section 4.3.5).

The Guideline Update Process

This guideline appraises and summarises the available evidence on the clinical care of people with suspected or con ﬁ rmed ACS. This evidence informs a set of recommendations to guide healthcare professionals in making diagnostic and therapeutic decisions. It replaces the National Heart Foundation of Australia & Cardiac Society of Australia and New Zealand: Australian Clinical Guidelines for the Management of Acute Coronary Syndromes 2016 [ 1 – 3 ].

The guideline was developed based on the Grading of recommendations, assessment, development, and evaluation (GRADE) methodology [ 4 ]. It is also informed by the 2016 National Health and Medical Research Council (NHMRC) Standards for Guidelines [ 5 ], adapting them where necessary to meet the speci ﬁ c requirements of this guideline.

Five expert groups, including a consumer advisory panel, directed and governed the development of this guideline. Members from diverse backgrounds and geographic regions were recruited between the last quarter of 2021 and ﬁ rst quarter of 2022. Clinical experts were selected based on their experience in guideline development and area of expertise. Expertise was sourced across the disciplines of cardiology, emergency medicine, general medicine, general practice, nursing, pharmacy, epidemiology, cardiac rehabilitation and public health.

Please see Supplementary Material A for full details on the governance arrangements, processes for establishing the expert groups, literature search and evidence synthesis, recommendation development using the GRADE methodology, and the public consultation and approvals process [ 6 ].

Development of Recommendations and Using this Guideline

Between the second and third quarter of 2022, the Expert Steering Group (ESG) and Expert Subgroups developed the guideline scope and clinical questions. These were prioritised based on current literature, gaps identi ﬁ ed in international guidelines, priorities and choices faced by healthcare professionals, and values and preferences of people with lived experience. The guideline scope was shared with reference group organisations and the consumer advisory panel for feedback. The clinical questions were expressed in patient/ population, intervention, comparison, outcome, time, setting (PICOTS) format. In the fourth quarter of 2022, an independent reviewer conducted the literature review based on these PICOTS questions.

The literature review sought published studies from January 2015 to December 2022. Evidence summaries were completed in the ﬁ rst quarter of 2023. They were supplemented with studies identi ﬁ ed from conference attendances, reference lists and database alerts. If relevant and pertinent, studies published after the literature search dates were also included.

Between the second and fourth quarter of 2023, the expert groups drafted the guideline content and recommendations. Guideline recommendations were developed using GRADE methodology. The GRADE approach offers a transparent and structured process for developing and presenting evidence summaries and recommendations [ 4 ]. In some instances, recommendations were adopted or adapted from existing international guidelines.

In the ﬁ rst quarter of 2024, an independent reviewer was commissioned to assess the comprehensiveness and balance of the scienti ﬁ c evidence, certainty of evidence and rationale to inform the wording and strength of the recommendations.

Table 1 provides a summary of GRADE de ﬁ nitions.

The GRADE methodology considers the importance of the recommendation, which is not necessarily related to the quality or certainty of the evidence. Rather, the importance re ﬂ ects the extent to which the recommendation will impact on the health status or quality of life of the target population. This allows for a strong recommendation to be made even if the certainty of the evidence is low.

Recommendations are categorised as ‘ consensus ’ where there is high certainty that the desirable effects of an intervention clearly outweigh its undesirable effects, but the body of supportive evidence is indirect and the application of the GRADE approach is inappropriate.

Consensus recommendations were informed by the expert opinion of the Expert Steering Group and Expert Subgroup members, with consideration of the evidence, values, preferences and resource use at the time of writing. Consensus was established when the majority of members supported the statement.

Table 1 GRADE de ﬁ nitions.

|Certainty of evidence|| |---|---| ||| | The certainty of evidence reflects the extent to which the confidence in the estimates of an effect is adequate to support a particular decision. Certainty of |What it means| |evidence|| |High|The authors are very confident that the true effect lies close to that of the estimate of the effect.| |Moderate| The authors are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. | |LOW|| || The authors' confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. | |Verylow|The authors have very little confidence in the effect estimate: the true effect is likely to be substantially| ||differentfrom the estimate of the effect.| |Strength of recommendation|| ||The strength of a recommendation reflects the extent to which the authors are confident that desirable effects of an intervention outweigh| |undesirable effects, or vice versa, across the range of people for whom the recommendation is intended. It is determined by considering the|| | balance between benefits and harms, certainty of evidence, variability or uncertainty in the values and preferences of the target population, and resource use. || ||| |Strength of|What it means| | recommendation|| |Strong|The authors are confident that the desirable effects of adherence to a recommendation outweigh the| || undesirable effects. It implies that most or all individuals will be best served by the recommended course of action. | |Weak|The authors concluded that the desirable effects of adherence to a recommendation probably outweigh the| ||undesirable effects but are not certain. It implies that not all individuals will be best served by the|

Abbreviation: GRADE, Grading of recommendations, assessment, development and evaluation.

Practice points are statements that are actionable and often describe the who, what, how, where and when of implementing a recommendation. Practice points can contain supporting information about a recommendation (e.g. medicine dosing). They may also include tools and tips that enhance implementation of the chosen intervention and/or its ef ﬁ cient use. Practice points are not actionable without related recommendations.

Practice points were developed with consideration of the geographical challenges in Australia and availability of resources in Australian healthcare settings. Where there were speci ﬁ c practice points, evidence and/or resources relevant to underserved populations, these were included under a separate subheading.

For each section in this guideline, recommendations are presented ﬁ rst for easy identi ﬁ cation. These are followed by a summary of the supporting evidence, which provides a rationale for the recommendations. Relevant practice points are subsequently presented at the end of each section.

This guideline should be read in conjunction with the Australian Commission for Safety and Quality in Health Care ACS Clinical Care Standard which informs quality indicators to drive better outcomes for all people living in Australia

[ 7 ]. Some sections provide suggested areas for further research.

Further details of the guideline development process can be found in Supplementary Material A3 .

Con ﬂ icts of Interest

Con ﬂ icts of interest are considered within a framework of:

' the relationship (direct or indirect) of the individual to any third party with interests in the guideline topic being considered ' the nature ( ﬁ nancial and non- ﬁ nancial) of the potential con ﬂ ict.

Con ﬂ icts of interest among the expert groups required appropriate management to ensure recommendations were not compromised. Processes employed by the Heart Foundation aimed to ensure the integrity of the guideline while striking an appropriate balance between interests in certain topics and the expertise required to make sound and meaningful recommendations.

More information on con ﬂ icts of interest management and a summary of all disclosures can be found in Supplementary Material A2 .

1. Preamble

1.1. Impact of ACS in Australia

Acute coronary syndromes (ACS) are a signi ﬁ cant public health concern in Australia, with substantial impacts on individuals, healthcare systems and society. In 2021, there were an estimated 57,300 acute coronary events among Australians aged 25 years and over, equating to approximately 157 events per day [ 8 ]. Hospitalisations related to ACS also remain high, with 92,400 admissions recorded in 2020 – 2021, representing over half of all coronary heart disease hospitalisations that year [ 8 ]. Tragically, coronary heart disease, which includes ACS, was the underlying cause of 17,300 deaths in 2021, accounting for $10\%$ of all deaths in Australia [ 8 ].

The economic burden of ACS is considerable. In 2017 – 2018, the ﬁ nancial cost of ACS events to Australian governments was estimated at $\S1.93\$ billion [ 9 ]. Disparities exist, with men experiencing rates of acute coronary events 2.3 times higher than women after adjusting for age [ 8 ]. Women, however, face unique challenges, including longer symptom duration, delays in receiving treatment and lower rates of secondary prevention medication use [ 10 – 12 ]. Furthermore, First Nations peoples experience coronary events at twice the rate of non-Indigenous Australians, highlighting ongoing inequities in healthcare access and outcomes [ 8 , 13 , 14 ].

The age-standardised rate of acute coronary events declined by $31\%$ between 2011 and 2018, progress has slowed for younger populations [ 14 ]. Encouragingly, improvements in care have been observed, with signi ﬁ cant reductions in in-hospital events and 6-month readmissions for people with ACS between 2000 and 2007 [ 9 ]. These trends underscore the need for continued investment in prevention, early detection and equitable access to high-quality care to further reduce the burden of ACS on Australians.

Speci ﬁ c recommendations to improve outcomes for these high-risk populations, including older people and/or those with frailty, are incorporated throughout the guideline wherever possible.

1.2. De ﬁ nitions and Terminology

A clear understanding of de ﬁ nitions and terminology is essential for accurate use of this guideline. ACS encompass both AMI and unstable angina (UA).

ACS may also be classi ﬁ ed as ST-segment elevation ACS (STEACS) and non-ST-segment elevation ACS (NSTEACS). NSTEACS encompasses both non-ST-segment elevation myocardial infarction (NSTEMI) and UA ( Figure 1 ), with NSTEMI and UA differentiated by the presence or absence of biomarker evidence of cardiomyocyte necrosis respectively.

This guideline has adopted the term acute coronary occlusion myocardial infarction (ACOMI) which includes people presenting with electrocardiogram (ECG) changes of either ST-segment elevation (STE) or other changes indicative of signi ﬁ cant epicardial artery acute coronary occlusion.

1.2.1. Fourth universal de ﬁ nition of myocardial infarction The Fourth universal de ﬁ nition of myocardial infarction (UDMI) bases the diagnosis of AMI on evidence of cardiomyocyte necrosis as detected by an elevated cardiac biomarker. Preferably, this is a high-sensitivity cardiac troponin (hs-cTn) T or I assay, with at least one value above the $99^{\mathrm{th}}$ percentile of the upper reference limit [ 15 , 16 ].

The currently accepted international criteria for diagnosing AMI are the detection of an increase and/or decrease in troponin, with one value above the upper reference limit, and at least one of the following [ 15 ]:

' symptoms of acute myocardial ischaemia ' new ischaemic ECG changes ' development of pathological Q waves on ECG ' imaging evidence of new loss of viable myocardium, or new regional wall motion abnormality consistent with an ischaemic aetiology ' intracoronary thrombus detected on coronary angiography or autopsy.

Type 1 myocardial infarction (MI) is spontaneous MI with coronary pathology and is characterised by atherosclerotic plaque rupture, ulceration, ﬁ ssure, or erosion with resulting intraluminal thrombus in one or more coronary arteries leading to decreased myocardial blood ﬂ ow and/or distal embolisation and subsequent myocardial necrosis [ 17 ]. The underlying coronary artery disease (CAD) may be nonobstructive or absent on angiography (myocardial infarction with non-obstructive coronary arteries [MINOCA]) [ 15 ].

Type 2 MI occurs when myocardial injury or necrosis is associated with an imbalance between myocardial oxygen supply and demand (usually driven by an increase in the latter) and may be seen in situations associated with hypotension, hypertension, tachyarrhythmia, bradyarrhythmia, anaemia, hypoxaemia, or pulmonary embolism. In contrast to type 1 MI, there is no new anatomical obstruction of the coronary vessels.

Acute or chronic myocardial injury may occur in both type 1 and type 2 MI. Myocardial injury occurs when there is evidence of elevated cardiac troponin (cTn) with at least one value greater than the $99^{\mathrm{th}}$ percentile upper reference limit, but in the absence of acute ischaemic symptoms. Myocardial injury is acute if there is a short-term rise and/or fall in troponin values, or chronic if the troponin level is stable.

Type 3 MI is described as MI resulting in death when biomarkers are not available.

Type 4 and 5 MI represent peri-procedural MI related to percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) respectively.

1.2.2. Revised de ﬁ nition of myocardial infarction

This guideline adopts re ﬁ ned de ﬁ nitions that align more closely with the clinical syndromes that characterise occlusive and non-occlusive MI [ 15 , 18 ].

In re ﬁ nements to the Fourth UDMI adopted in this guideline, an identical clinical picture to type 1 MI may be caused by non-atherosclerotic mediated coronary occlusion

such as SCAD, coronary embolism, or coronary vasospasm or microvascular dysfunction ( Figure 2 ), which are all associated with coronary pathology.

Such conditions (classi ﬁ ed as type 2 MI in the Fourth UDMI) result in a spontaneous reduction in myocardial oxygen supply, with the clinical presentation, investigation ﬁ ndings and early management often indistinguishable from those associated with spontaneous atherosclerotic plaque events. Hence, they are classi ﬁ ed as forms of occlusive MI in this guideline ( Figure 2 and section 2.1.2 History of the presenting complaint ) [ 19 – 21 ].

In further re ﬁ nements to the Fourth UDMI, MI due to oxygen supply/demand mismatch without acute coronary occlusion may be further subclassi ﬁ ed according to the presence or absence of ﬁ xed obstructive CAD.

Acute coronary occlusion causes downstream MI (i.e. ACOMI) in the absence of timely reperfusion. Importantly, ACOMI may present as ST-segment elevation myocardial infarction (STEMI) or STEMI equivalents (section 2.2.1 ECG ﬁ ndings of acute coronary occlusion myocardial infarction ) [ 22 ]. This guideline uses the term ACOMI to highlight STEMI equivalents, which are often under recognised or missed in emergency settings.

This guideline predominantly focuses on managing people with MI due to atherosclerotic plaque rupture, ulceration, ﬁ ssure, or erosion with resulting intraluminal thrombus in one or more coronary arteries leading to decreased myocardial blood ﬂ ow and/or distal embolisation and subsequent myocardial necrosis.

1.2.3. De ﬁ nition of major adverse cardiovascular events In people presenting with suspected ACS, the risk of an index MI and major adverse cardiovascular events

(MACE) over the next 30 days should be assessed as low, intermediate or high. In people with con ﬁ rmed ACS, MACE generally includes AMI, cardiac death, and stroke.

1.2.4. De ﬁ nition of unstable angina

UA is myocardial ischaemia at rest or on minimal exertion in the absence of acute cardiomyocyte injury/necrosis. This is an important clinical diagnosis based upon symptoms, with or without ECG changes in the absence of elevated troponin concentrations.

Since the introduction of hs-cTn assays, the prevalence of UA has decreased, likely due to greater assay precision allowing detection of low-range changes in troponin concentrations [ 23 – 26 ].

1.2.5. Myocardial infarction with non-obstructive coronary arteries

MINOCA is when a person presents with symptoms suggestive of ACS, demonstrates troponin elevation and has non-obstructed coronary arteries at the time of coronary angiography (no coronary artery stenosis ${\geq}50\%$ in any major epicardial vessel) and there is no speci ﬁ c alternate diagnosis for the clinical presentation (e.g. pulmonary embolism or myocarditis) [ 27 , 28 ].

MINOCA is a working, rather than a ﬁ nal, diagnosis and further investigations are essential to establish the underlying cause. Cardiac magnetic resonance imaging (MRI) is valuable to establish the presence of MI and to exclude differential diagnoses such as myocarditis. If atherosclerotic heart disease is likely, the person should be managed with appropriate secondary prevention medicines and lifestyle interventions.

![Acutemyocardialinjurywithsignsand/orsymptomsofischaemia MIwith acute MI due to oxygen supply/demand coronaryocclusion mismatchwithout acutecoronaryocclusion Plaquerupture/erosion Spontaneous coronary Coronary Vasospasmor Withfixed Withoutfixed withthrombus arterydissection embolism microvasculardysfunction obstructiveCAD obstructiveCAD ](https://venus-llm-1258344701.cos-internal.ap-guangzhou.tencentcos.cn/userUpload/is-62e36cd9/2025-04-10/1306983d-8578-4e97-9f06-96a15936fc91/1306983d-8578-4e97-9f06-96a15936fc91.jpg?q-sign-algorithm=sha1&q-ak=AKID61g5D5fy1TjiRv84nEOHtFJ8gyzjCPL0&q-sign-time=1744240805%3B1744244405&q-key-time=1744240805%3B1744244405&q-header-list=host&q-url-param-list=&q-signature=341132c3be00ad3a54d6be4e1fbfff706765f42c) Figure 2 Revised classi ﬁ cation of MI. Adapted from de Lemos et al. [ 18 ]. Both types of MI may present with ECG changes of ST-segment elevation (STEMI) or non-ST-segment elevation (NSTEMI). Abbreviations: CAD, coronary artery disease; MI, myocardial infarction.

1.3. Shared Decision Making

Shared decision making involves open communication between a person and their healthcare provider to deliver appropriate, person-centred care. Shared decision making combines a person ’ s values, goals and preferences with the best available evidence about bene ﬁ ts and potential risks of healthcare interventions [ 29 ].

A three-step approach to implement shared decision making in clinical practice involves introducing choice, describing options (often with decision aids), and assisting people to explore their preferences [ 30 ].

Shared decision making should be implemented across the care continuum for people with suspected or con ﬁ rmed ACS, including risk assessment, choice of reperfusion strategy and discharge planning. Shared decision making enables alignment between peoples ’ values and proposed treatment options [ 31 ].

Shared decision making is well supported and encouraged in cardiovascular research and practice, although further study is needed on optimal implementation [ 32 – 36 ].

1.4. Collaborative Approaches to Care for First Nations Peoples

A holistic, collaborative approach is crucial to the delivery of culturally appropriate, best practice care for First Nations peoples with suspected or con ﬁ rmed ACS. Shared decision making is central to this but also includes the way healthcare settings and services are designed and interact. A truly collaborative approach is one that ensures First Nations peoples with ACS feel culturally safe at every point of contact with the health system.

It is the responsibility of all healthcare professionals along the ACS care continuum to be culturally competent and to embed shared decision making in their clinical practice. Cultural competence refers to a set of consistent values, behaviours and actions that enable effective delivery of healthcare across cultures [ 37 ].

Aboriginal and Torres Strait Islander health practitioners, Aboriginal health workers and Aboriginal liaison of ﬁ cers, where available, should be involved in a First Nations person ’ s care as early as possible. Aboriginal and Torres Strait Islander health practitioners and Aboriginal health workers (collectively referred to in this guideline as First Nations health practitioners) play a critical role in the ongoing management and follow up of First Nations peoples with con ﬁ rmed or suspected ACS. These practitioners work in tertiary, secondary and primary care settings, including Aboriginal Community Controlled Health Organisations. Particularly in remote communities, Aboriginal health workers are vital to the delivery of primary health care.

Aboriginal liaison of ﬁ cers support the First Nations person and their family by acting as an intermediary with healthcare professionals. They help to overcome cultural and communication barriers to care and provide support in navigating the hospital system. Crucially, Aboriginal liaison of ﬁ cers also

help facilitate the transition to outpatient care, acting as the central liaison between the person ’ s specialist team and general practitioner.

Speci ﬁ c practice points for First Nations peoples have been embedded throughout this guideline. These practice points recognise the different health outcomes for First Nations peoples that have resulted from dispossession, discrimination, disadvantage and disempowerment. Several resources are available on the Heart Foundation website to guide yarning and shared decision making between First Nations peoples and their healthcare providers.

2. Assessment and Diagnosis

2.1. Assessment of People with Suspected ACS

Assessment of ACS incorporates the following:

' ECG ﬁ ndings ' clinical ﬁ ndings from history and physical examination ' troponin testing.

These observations are combined to either diagnose or inform risk assessment which will guide the location and timing of further investigations, management, and appropriate follow-up. Rapid identi ﬁ cation of people with ACS is crucial as many treatments are time sensitive and earlier intervention improves outcomes. However, only a minority of people presenting with acute chest pain to the emergency department (ED) will have a ﬁ nal diagnosis of ACS [ 38 , 39 ].

Among those presenting with acute chest pain to the ED in whom ACS is suspected, ${<}5\%$ will have STEMI, $5–10\%$ NSTEMI, $5–10\%$ UA, $15{-}20\%$ other cardiac conditions, and $50–60\%$ non-cardiac conditions [ 39 – 42 ]. While a de ﬁ nitive diagnosis may be made at index presentation, most diagnoses will be of a non-cardiac condition or remain unclear and may require further follow-up to complete assessment as an outpatient [ 16 ].

For this reason, risk assessment for ACS is the key initial goal, rather than achieving a rule in or rule out diagnosis relating to ACS which may not be possible in many people (section 2.4 Risk Assessment and Clinical Decision Pathways for Suspected ACS ).

The hierarchy of assessment in suspected ACS is as follows:

1. Identify people with ACOMI (STEMI and STEMI equivalents). 2. Identify people with NSTEMI. 3. Identify people with UA at high risk for 30-day MACE. 4. Identify people with underlying CAD in whom ACS is not con ﬁ rmed.

Assessment for people with suspected ACS within an ED setting is described in the following sections.

Speci ﬁ c guidance for people presenting in regional/ remote and primary care settings is given in section 2.10 Primary Care and Regional and Remote Presentations .

2.1.1. Initial assessment summary

The ﬁ rst steps in the assessment of people presenting to a healthcare setting with symptoms suspicious for ACS include the following (see practice points for setting considerations):

' Vital sign measurements including blood pressure, heart rate, respiratory rate and peripheral oxygen saturation should be recorded. ' An ECG should be reviewed by a clinician experienced in ECG interpretation to examine for evidence of ACOMI

within 10 minutes of presentation (section 2.2 Initial ECG Assessment ). ' If a diagnosis of ACS is considered likely, further investigations including troponin testing should be performed (section 2.3 Biomarkers and section 2.4 Risk Assessment and Clinical Decision Pathways for Suspected ACS ). ' Promptly identify people with ACOMI suitable for urgent reperfusion. ' People without clinical symptoms of ACOMI but with ECG evidence of cardiac ischaemia, and/or people who are otherwise strati ﬁ ed as high risk of index MI or 30-day MACE (section 2.4.1 Clinical decision pathways ), should have continuous cardiac monitoring. ' In people who are symptomatic and/or haemodynamically compromised, ECGs should be performed at (a minimum of) 15-minutes intervals until the symptoms have resolved. a. Additional ECGs should be performed if symptoms recur, there are changes in character or a change in their clinical condition. ' If there is no evidence of ACOMI on ECG, a targeted history and physical examination should be performed and differential diagnoses considered, particularly time critical emergencies including ruptured aortic aneurysm, pulmonary embolism, or pneumothorax ( Table 2 ) [ 43 , 44 ]. a. A chest X-ray may be useful in identifying some other causes, including pneumonia or pneumothorax, and to assess for cardiac size or evidence of cardiac failure. Acquiring a chest X-ray should not delay urgent reperfusion. This guideline does not apply to these other time-critical emergencies [ 43 , 44 ].

Table 2 Differential diagnoses of acute chest pain.

|Cardiac: ACS|AMI, unstable angina.| |---|---| |Cardiac: Other|Stable angina, myopericarditis,| ||tachyarrhythmia, hypertensive emergencies,| ||severe aortic stenosis, Takotsubo| ||cardiomyopathy, cardiac trauma.| | Pulmonary| Pulmonary embolism, pneumothorax| ||(including tension), infection (pneumonia,| || bronchitis), pleuritis.| | Vascular |Aortic dissection, expanding aortic| | aneurysm, sickle cell crisis.|| ||| || Gastrointestinal Oesophagitis, reflux, spasm, rupture, peptic| ||ulcer disease, pancreatitis, cholecystitis and| ||biliary disease.| | Other | Musculoskeletal disease (including| ||costochondritis, trauma), anxiety disorder,| ||| || infectious disease (including herpes zoster). |

Abbreviations: ACS, acute coronary syndromes; AMI, acute myocardial infarction.

' If the ECG is normal, and a person ’ s symptoms are clearly attributable to a non-cardiac cause, this guideline no longer applies. Clear communication with people explaining they do not have ACS is essential and may reduce a person ’ s and their carers ’ anxiety (section 2.9 Discharge Planning and Advice ).

The following sections describe the subsequent processes of assessment and diagnosis if ACS is suspected.

2.1.2. History of the presenting complaint

After assessing for high-risk features on ECG and/or abnormal vital signs, a focused history is required to evaluate for symptoms suggestive of myocardial ischaemia, time of onset, and risk factors for ACS.

As the history is pivotal to assessing potential risk of ACS, barriers to clear clinician-person communication such as cultural issues, language differences, or hearing de ﬁ cits should be addressed [ 45 ]. Engaging with appropriate translator services or culturally competent health workers is strongly recommended (Practice points: First Nations peoples).

Chest pain, angina equivalents and associated symptoms Chest pain due to myocardial ischaemia is most often described as substernal discomfort or pressure which may radiate to the neck, arms or jaw and is exacerbated by exertion and relieved with rest after 15 or 20 minutes [ 46 ]. While chest pain is the most common symptom of ACS, it is not always present. In addition, many people deny actual chest pain, and refer to discomfort, pressure or heaviness which in this guideline are included under the umbrella term of chest pain.

Descriptions of myocardial ischaemia pain vary considerably, and consideration needs to be given to sex, ethnic background and culture. The description of the pain may help in determining if the person ’ s presentation is consistent with myocardial ischaemia or unlikely to be ACS ( Figure 3 ).

A response or lack of response to treatment (such as glyceryl trinitrate, standard analgesia or anti-acids) should not be used as a diagnostic criterion for ACS (section 2.5 Initial Therapeutic Management ) [ 47 ].

Shortness of breath, fatigue, nausea, diaphoresis or vomiting are relatively common in people with ACS, with women more likely than men to present with such symptoms (Practice points: Women). Some people, particularly older adults and those with diabetes, may not describe any chest pain or discomfort, instead only reporting associated symptoms (sometimes referred to as angina or chest pain equivalents).

The terms typical and atypical have previously been used to describe cardiac ischaemic symptoms. However, given their wide variation, cardiac, possible cardiac or non-cardiac symptoms are now recommended terms (Practice points: Women and Older adults) [ 16 ].

Factors associated with myocardial infarction types An absence of risk factors for CAD does not exclude ACS. The risk factors for the different types of AMI are listed in Table 3 .

![High Central,squeezing gripping,pressure, tightness,heaviness, exertional/stress-related, retrosternal,radiation toarms,neckorjaw Left-sided,aching,dull Probability ofischaemia Stabbing Right-sided,burning, ripping,tearing Sharp,shifting,fleeting, pleuritic,positional Low ](https://venus-trag-1258344701.cos-internal.ap-guangzhou.tencentcos.cn/userUpload/is-62e36cd9/2025-04-10/86526dae-04f9-46bb-b6b5-b1f4f406591c/86526dae-04f9-46bb-b6b5-b1f4f406591c.jpg?q-sign-algorithm=sha1&q-ak=AKID61g5D5fy1TjiRv84nEOHtFJ8gyzjCPL0&q-sign-time=1744240805%3B1744244405&q-key-time=1744240805%3B1744244405&q-header-list=host&q-url-param-list=&q-signature=d13b822ad27f510def0b97d45050c24db7171ddc) Figure 3 Probability of cardiac ischaemia based on commonly used descriptors of chest pain.

Practice points

Women

' Recognise chest pain as the most common symptom in women with ACS, occurring at similar rates to men. Be aware that associated symptoms in women may include jaw, neck, shoulder or back pain, fatigue/tiredness, nausea or vomiting, dizziness, indigestion, shortness of breath [ 57 – 59 ]. ' Remain vigilant to the risk of misdiagnosis in women presenting with ACS [ 60 , 61 ]. Women are more likely than men to be misdiagnosed with non-cardiac pain and are more likely to experience delays in receiving life-saving procedures in hospital [ 10 ]. Healthcare professionals should consider potential sex bias when interpreting symptoms [ 62 ]. ' Increase awareness of sex differences in ACS symptoms and presentation patterns. Clinical education and recognition of these differences may improve diagnosis and management of ACS in women. ' Consider SCAD as a potential cause of ACS, particularly in young to middle-aged women. Refer to section 3.9 Treatment for Spontaneous Coronary Artery Dissection for management recommendations [ 50 ].

Older adults

' Recognise that older age ( ${>}75$ years) is an independent risk factor for ACS and other conditions with similar to ACS. Comorbidities are also more prevalent in this age group, which may complicate diagnosis and management [ 63 ].

Table 3 Factors associated with spontaneous MI with coronary pathology and oxygen supply/demand imbalance.

Factors associated with atherosclerosis [ 48 , 49 ] :

' Older age ( ${>}75$ years) ' Diabetes mellitus ' Hypertension ' Hypercholesterolaemia ' Obesity ' Smoking ' Socioeconomic disadvantage ' Family history of premature ASCVD ( ﬁ rst-degree male relative aged ${<}55$ years; ﬁ rst-degree female relative aged ${<\!65}$ years)

Selected additional risk factors for atherosclerosis (for full details refer to www.cvdcheck.org.au [ 49 ] :

' Chronic in ﬂ ammatory conditions, such as psoriasis, rheumatoid arthritis, lupus, or systemic sclerosis ' Familial hypercholesterolaemia con ﬁ rmed by genetic testing ' Chronic kidney disease ( $\mathrm{eGFR~15-59~mL/min}/1.73~\mathrm{m}^{2}$ with or without albuminuria; not treated with dialysis or kidney transplantation) ' Severe mental illness (de ﬁ ned as a current or recent mental health condition requiring specialist treatment, whether received or not, in the ﬁ ve years prior to risk assessment) ' Ethnicity (e.g. South Asian or First Nations ancestry) ' History of premature (before age 40 years) or early (before age 45 years) menopause ' History of pregnancy-associated conditions that increase later ASCVD risk, such as hypertensive disorders of pregnancy (e.g. pre-eclampsia) and gestational diabetes ' Polygenic risk score indicating higher risk of atherosclerosis ' COVID-19 (historical or current infection)

Factors associated with SCAD [ 50 , 51 ] :

' Female sex ' Younger age ( $\mathord{\cdot}\mathord{<}50$ years) ' Lack of cardiovascular risk factors ' Pregnancy or postpartum ' Fibromuscular dysplasia ' Inherited connective tissue disorders

Factors associated with coronary embolism [ 52 ] :

' Aortic or mitral valve, left atrial appendage or left ventricle thrombus, vegetation or neoplasm ' Patent foramen ovale, atrial septal defect or pulmonary arteriovenous malformation with a venous source (e.g. deep vein thrombosis) ' Atrial ﬁ brillation without adequate anticoagulation

Factors associated with coronary vasospasm [ 53 – 55 ] :

' Smoking ' Older age ( ${>}75$ years) ' Allergy ' Chemotherapy (5- ﬂ uorouracil) ' Some illicit drugs (cocaine, methamphetamine)

Table 3. Continued

Factors associated with coronary microvascular dysfunction

[ 56 ] :

' Female sex (especially post-menopausal) ' Atherosclerotic disease ' Chronic in ﬂ ammation (e.g. systemic lupus erythematosus, rheumatoid arthritis) ' Myocardial diseases B Hypertrophic cardiomyopathy B Dilated cardiomyopathy B Anderson-Fabry ’ s disease B Amyloidosis B Myocarditis B Aortic stenosis

Factors associated with oxygen supply/demand imbalance ( $'+/-$ atherosclerosis) [ 15 ] :

' Severe anaemia ' Hypotension/shock ' Sustained tachycardia or tachyarrhythmia ' Sustained bradycardia or bradyarrhythmia ' Respiratory failure ' Sepsis ' Pulmonary embolism ' Critical illness

Note: Takotsubo cardiomyopathy is not classi ﬁ ed as MI and is not discussed in this guideline. Abbreviations: AIDS, acquired immunode ﬁ ciency syndrome; ASCVD, atherosclerotic cardiovascular disease; eGFR, estimated glomerular ﬁ ltration rate; HIV, human immunode ﬁ ciency virus; MI, myocardial infarction; SCAD, spontaneous coronary artery dissection.

Be aware that chest pain may not be the primary symptom of AMI in older adults. In this population, including in those with STEMI and STEMI equivalents, angina equivalents (such as shortness of breath, fatigue, or dizziness) are commonly observed [ 64 – 67 ].

First Nations peoples

' Recognise that First Nations peoples with ACS are typically younger, have higher rates of cardiac risk factors, experience lower intervention rates and face poorer outcomes compared with non-Indigenous Australians. These disparities highlight the importance of tailored interventions and equitable care [ 13 , 68 , 69 ]. ' Provide access to First Nations healthcare practitioners, liaison of ﬁ cers, and culturally appropriate interpreter services within hospitals. This facilitates accurate historytaking and improves quality of care [ 13 , 68 ]. ' Incorporate culture-speci ﬁ c attitudes and values into health promotional tools and offer culturally appropriate pastoral care. These steps can help to bridge cultural gaps and enhance engagement with First Nations peoples [ 13 , 68 ]. ' Prioritise education on cultural awareness, competency and safety for healthcare professionals. Such education has

been shown to reduce unconscious bias and improve health outcomes for First Nations peoples [ 13 , 68 ].

2.2. Initial ECG Assessment

Recommendations

|Recommendation| Strength of recommendation | Certainty O1 evidence | |---|---|---| |||| | In people presenting with|Consensus|| |chest pain or other symptoms||| | suggestive of ACS, record and||| | assess an ECG for evidence of||| |ACOMI within 10 minutes of||| |first clinical contact.||| |||| | In people with suspected ACS,|Consensus|| |record and assess additional||| |ECGs if symptoms persist,||| |change, or recur, or there is||| |diagnostic uncertainty. For||| |those with ongoing ischaemic||| |symptoms and an inconclusive||| |standard 12-lead ECG, record||| |and assess further ECGs with||| |right-sided and/or posterior||| | leads. ||| | In people with ongoing|Strong|LOW| |ischaemic symptoms or||| |haemodynamic compromise||| | or new ischaemic findings on||| |ECG, continuous cardiac||| |monitoring and defibrillator||| |availability is recommended||| |while assessment for ACOMI||| | continues.|||

Evidence supporting the recommendations

The priority is to identify people with ACOMI as soon as possible to expedite reperfusion. Urgent reperfusion can save viable myocardium and reduce morbidity and mortality.

Recording and interpreting the ECG is the most important initial investigation and should be performed within 10 minutes of clinical contact for all people presenting with chest pain or other symptoms of ACS [ 70 ]. As ECGs in people with ACOMI can show different patterns ( Figure 4 ), they should be examined by a clinician experienced in ECG interpretation. In remote areas, an established process that enables rapid ECG interpretation is required if an experienced clinician is unavailable on site [ 71 ].

If ACOMI is not initially identi ﬁ ed, the ECG should be further examined for features associated with higher likelihood of evolving to ACOMI or signs of myocardial

ischaemia (section 2.2.2 High-risk ECG ﬁ ndings ; 2.2.3 Other signs of myocardial ischaemia on ECG ; and Figure 4 ). If available, pre-hospital ECGs or ECGs recorded during previous presentations should be compared to assess for new or dynamic changes.

If features of ongoing ischaemia are present or people are strati ﬁ ed as high risk, close clinical and continuous monitoring of cardiac rate and rhythm with 3 – 5 lead electrodes of an ECG monitor should be initiated to assist early recognition of arrhythmias or cardiac arrest (section 2.4 Risk Assessment and Clinical Decision Pathways for Suspected ACS ) [ 72 ]. The indications for continued monitoring should be reviewed regularly.

For people with an initial non-ischaemic ECG, resolved symptoms and initial troponin concentration equal to or below the sex-speci ﬁ c $99^{\mathrm{th}}$ percentile, continuous cardiac monitoring is not required (section 2.3 Biomarkers and 2.4 Risk Assessment and Clinical Decision Pathways for Suspected ACS ). However, repeated ECGs should be performed either at prescribed intervals (e.g. hourly), when repeated troponin samples are collected or as guided by changes in a person ’ s symptoms or clinical condition.

2.2.1. ECG ﬁ ndings of acute coronary occlusion myocardial infarction

STE is the key ECG criterion required to institute a reperfusion strategy for people with signs or symptoms of myocardial ischaemia ( Figure 4 A) [ 73 ]. STE is not speci ﬁ c to ACOMI and may occur in other disease states, both cardiac and non-cardiac [ 74 ]. Cardiac conditions with STE without acute coronary occlusion include pericarditis, left ventricular hypertrophy (LVH), left ventricular aneurysm, left bundle branch block (LBBB), right ventricular pacing, Takotsubo or other cardiomyopathies and Brugada patterns. Non-cardiac STE conditions include normal variant STE (early repolarisation), pulmonary embolism, hyperkalaemia, hypothermia and raised intracranial pressure.

In the clinical context of myocardial ischaemia, STE should be assumed to represent ACOMI until excluded.

Recognised ECG patterns of acute coronary occlusion myocardial infarction

Comparison of ECGs with coronary angiogram results have revealed multiple ECG patterns of ACOMI beyond traditional STE criteria [ 22 , 75 , 76 ]. Recognition of the following patterns improves ECG sensitivity for acute coronary occlusion and should prompt consideration of ACOMI warranting reperfusion ( Figure 4 ) [ 77 ]. This may require supplemental lead ECGs to interrogate electrically subtle or silent areas of the heart such as the inferior, basal, posterior and right ventricular walls ( Table 4 ). Notable ECG ﬁ ndings include:

' High lateral MI manifesting with STE in non-contiguous leads due to occlusion of the ﬁ rst diagonal branch of the left anterior descending coronary artery ( Figure 4 B) (referred to as the “ South African ﬂ ag sign ” ) [ 78 , 79 ].

||Criteria| Supporting information and illustration | Recommendation for clinical action || |---|---|---|---|---| | A.Regional STE with reciprocal STD | STE ≥1 mm at the J-point in two contiguous leads in all leads other than V2-4. |Normal|| Activate reperfusion pathway | |||||| |||||| |B. High lateral MI| STE I, aVL, V2 STD III(+/-II, aVF) Subtle STE V5, V6 and reciprocal changes in aVF may be seen. ||| Activate reperfusion pathway | |C.Posterior MI| Precordial STD ≥0.5 mm V1-3 Confirm with posterior leads (V7,8,9) with findings of STE: ≥0.5 mm in women and men ≥40 years | V7,8,9 supplementary lead placement || Activate reperfusion pathway | |||||| |D. Right ventricular| STE ≥0.5 mm in any right-sided chest lead (V3R-V6R), but particularly V4R. | Right precordial supplementary lead placement || Activate reperfusion pathway | | E.De Winter Twaves |STE ≥1 mm in men ||||

Figure 4 ECG ﬁ ndings consistent with acute coronary occlusion myocardial infarction (ACOMI).

Abbreviations: ECG, electrocardiogram; LBBB, left bundle branch block; MI, myocardial infarction; STD, ST-segment

depression; STE, ST-segment elevation.

' ST-segment depression ${\geq}0.5\ \mathrm{mm}$ in leads V1 – V3 due to ACOMI of the posterior aspect of the heart should prompt recording of posterior leads ( Figure 4 C) [ 80 – 82 ]. ' STE in lead V1 due to an isolated right ventricular MI should prompt recording of right-sided ECG leads ( Figure 4 D) [ 15 , 83 , 84 ]. ' De Winter pattern ( Figure 4 E) [ 85 ]. ' Transient STE, manifesting as STE in ${\geq}2$ contiguous leads of ${\geq}0.5~\mathrm{\mum}$ that resolves spontaneously, or after aspirin

and glyceryl trinitrate administration, may represent transient occlusion. These people should continue to be observed with continuous cardiac monitoring and serial ECGs.

Detecting new ST-segment elevation with a baseline abnormal ECG ECG evidence for ACOMI may be dif ﬁ cult to discern in people with abnormal baseline ECGs, such as LBBB, right ventricular pacing or LVH.

Table 4 ECG leads associated with cardiac regions.

|Cardiac region|Leads with STE| Reciprocal STD | |---|---|---| |||| |Anterior|V3，V4|None| |Anterolateral|1, aVL V3-V6|I1, III aVF| |Anteroseptal|V1-V4|None| |Septal|V1，V2|None| |Inferior|II, III, aVF|I,aVL| | Right ventricular|Right-sided|| ||chest leads V3-6|| |Posterior|Posterior leads V7-9|V1-V3| |Lateral|I, aVL,V5, V6|I1, III, aVF| |High lateral|1,aVL (V2)|III (II, aVF)|

Abbreviations: ECG, electrocardiogram; STE, ST-segment elevation; STD, ST-segment depression.

The validated Modi ﬁ ed Sgarbossa criteria improves diagnosis of STE in people with LBBB or right ventricular pacing with a speci ﬁ city of $99\%$ and a sensitivity of $80\%$ ( Figure 4 F) [ 86 – 88 ]. The modi ﬁ cation entails excessively discordant STE with an amplitude ${>}25\%$ of the depth of the preceding S wave in any lead with no scoring required.

There are currently no validated methods to discern STE of ACOMI from STE seen with LVH or hypertrophic cardiomyopathy. However, clinical suspicion for ACOMI should be high in the presence of haemodynamic compromise and/ or symptoms consistent with ACS.

In people with LVH, comparison with previous ECGs should be performed. If unavailable, continuous cardiac monitoring with close clinical observation and serial ECGs are required to monitor for development of acute coronary occlusion. Expert consultation should be sought for people with persisting ischaemic symptoms with equivocal ECG ﬁ ndings of ACOMI.

2.2.2. High-risk ECG ﬁ ndings

Acute coronary occlusion is a dynamic process which may not be evident on the initial ECG. Certain ECG patterns are associated with potential progression to ACOMI. These patterns call for prompt and continuous clinical and ECG monitoring.

Wellens T waves : characteristic T wave inversions in precordial leads. In a person in whom symptoms have resolved, this pattern may represent a reperfusion syndrome associated with a critical stenosis of the left anterior descending artery, known as Wellens syndrome ( Figure 5 A) [ 89 ]. Avoid provocative testing (e.g. exercise stress testing) and strongly consider invasive coronary angiography. If/when ischaemic symptoms return, the ECG recorded during symptoms will pseudo-normalise with more upright T waves.

Diffuse ST-segment depression across multiple leads with STE in aVR : may represent global ischaemia of various

etiologies including a left main occlusion, triple vessel disease or oxygen supply/demand mismatch ischaemia ( Figure 5 B) [ 90 ]. People with persisting symptoms with no identi ﬁ able alternative causes of ischaemia or who do not respond to treatment of alternative causes (e.g. hypoxia, anaemia, hypotension) should be considered for coronary angiography [ 91 ].

Hyperacute T waves : symmetrical, broad-based T waves disproportionately large to the preceding QRS complex can be the ﬁ rst ECG ﬁ nding of an evolving MI, although its prognostic signi ﬁ cance has been questioned ( Figure 5 C) [ 92 , 93 ]. These people should be subject to close clinical and continuous cardiac monitoring and serial 12-lead ECGs to examine for signs of ACOMI. An important differential diagnosis is hyperkalaemia ( Figure 5 C).

2.2.3. Other signs of myocardial ischaemia on ECG

Other ECG ﬁ ndings in a person with suspected myocardial ischaemia which should prompt continuous cardiac monitoring and consideration of treatment for NSTEACS are as follows.

' ST-segment depression : ${\geq}0.5\,\mathrm{\mum}$ at the J-point in ${\geq}2$ contiguous leads which is horizontal or down sloping ( Figure 5 D). The deeper and more widespread the depression, the more severe the ischaemia [ 94 , 95 ]. STsegment depression in contiguous leads should be ﬁ rst considered as reciprocal change of ACOMI and the ECG examined for corresponding STE, as ST-segment depression secondary to subendocardial ischaemia does not generally localise to a regional coronary territory ( Figure 4 , Figure 5 and Table 4 ) [ 96 ]. Although ST-segment depression occurs in other conditions (e.g. LVH, hypokalaemia, digoxin use), a systematic review found it to be highly speci ﬁ c $(97.2\%–99.3\%)$ ) but poorly sensitive $(16.6\%{-}20.0\%)$ ) for ischaemia [ 97 ].

' T wave abnormalities: including dynamic inversion or ﬂ attening ( Figure 5 E). New T wave inversion compared to a previous ECG or dynamic T wave changes during serial ECGs may represent ischaemia. Speci ﬁ city of T wave inversion for ischaemia is higher in the context of other signs of ischaemia on the ECG [ 98 ].

Computer-assisted ECG interpretation

No international standardised system for computer interpretation of ECGs currently exists. ECG machine manufacturers use different algorithms with varying sensitivity and speci ﬁ city for diagnosing cardiac conditions. Computer errors speci ﬁ c to ACS and ACOMI diagnosis include attribution of Q waves in LVH, LBBB, and/or dilated or hypertrophic cardiomyopathy to ACOMI. Other errors include an inability to discriminate STE of early repolarisation, pericarditis, or LBBBs from ACOMI [ 99 ]. ECG interpretation by a clinician who can incorporate the person-speci ﬁ c clinical context into the assessment is vital.

||Criteria| Supporting information and illustration | Recommendation for clinical action || |---|---|---|---|---| |A.Wellens criteria| Isoelectricorminimallyelevated J-point |||| |A.Wellens criteria| Isoelectricorminimallyelevated J-point |||| |A.Wellens criteria| Isoelectricorminimallyelevated J-point |||| |A.Wellens criteria| Isoelectricorminimallyelevated J-point ||||

Figure 5 High-risk ECG ﬁ ndings for ACS and ﬁ ndings suggestive of cardiac ischaemia.

Abbreviations: ECG, electrocardiogram; NSTEACS, non-ST-segment elevation acute coronary syndromes; STD, ST-segment depression; STE, ST-segment elevation; TWI, T wave inversion.

2.2.4. Continuous ECG monitoring

In people without ongoing symptoms, normal or nonischaemic ECG changes and initial normal troponin values, continuous ECG monitoring is not required. High-risk features in people with suspected ACS who require ongoing ECG monitoring are listed in Table 5 .

Practice points

' Do not rely on an initial normal ECG to exclude ACS. If myocardial ischaemia is strongly suspected, record and interpret serial ECGs.

Table 5 High-risk clinical features for people with suspected ACS requiring ongoing ECG monitoring.

Haemodynamic instability or cardiogenic shock Recurrent or ongoing chest pain refractory to medical treatment Cardiac arrest Recurrent dynamic ST-T wave changes or other changes consistent with myocardial ischaemia or infarction on ECG Arrhythmias (e.g. sustained ventricular tachycardia, high degree atrioventricular block) Mechanical complications of MI (e.g. new systolic murmur) Acute heart failure Abbreviations: ACS, acute coronary syndromes; ECG, electrocardiogram; MI, myocardial infarction.

' Do not delay treatment decisions/treatment in people with symptoms of ischaemia and clear evidence of ACOMI on ECG, while waiting for troponin test results.

' Do ensure consistent lead placement when performing serial ECGs to prevent artefactual errors in interpretation.

2.2.5. Future direction

Arti ﬁ cial intelligence (AI) and machine learning applied to ECG interpretation and linked with clinical data are currently being researched with the aim of delivering a more accurate and timely assessment of ACS and ACOMI [ 100 ].

2.3. Biomarkers

Recommendations

|Recommendation| Strength of recommendation | Certainty of evidence High | |---|---|---| |||| |In people with| Strong|| |suspected ACS,||| |evaluation with||| |high-sensitivity cardiac||| |troponin (hs-cTn)||| |||| |Elevated hs-cTn values|Consensus|| | should be defined using||| |sex-specific >99th||| | percentiles. ||| |Apply the assay-|Consensus|Consensus| | specific troponin values||| |relevant to the cTn||| | assay being used.||| |||| |When evaluating|Consensus|| |changes (deltas) in||| |troponin values, serial||| |results from a single||| | assay must be used.|||

Evidence supporting the recommendations

Cardiac troponin I (cTnI) or cardiac troponin T (cTnT) is the biomarker of choice in the diagnosis of ACS due to its organ-speci ﬁ c amino acid sequence, parts of which act as targets for assays using monoclonal antibodies [ 15 , 101 , 102 ].

Cardiac troponin assays have evolved from the 1990s to deliver improved sensitivity in detecting troponin. Currently, the most analytically sensitive assays preferred for clinical use are high-sensitivity assays [ 15 , 103 ]. A highsensitivity assay is more precise than earlier assays and can detect very low troponin concentrations, with measures of imprecision or $\%$ coef ﬁ cient of variation of ${\leq}10\%$ at the sexspeci ﬁ c $99^{\mathrm{th}}$ percentiles.

Evaluation with hs-cTn assays enable more rapid detection or exclusion of myocardial injury and increase diagnostic accuracy for MI compared with earlier generation of cTn assays called contemporary (conventional) troponin assays. The ability to detect very low troponin values with accuracy has been used to achieve safe, early rule out of MI and rapid discharge from the ED based on assay-speci ﬁ c metrics lower than the $99^{\mathrm{th}}$ percentile (section 2.4 Risk Assessment and Clinical Decision Pathways for Suspected ACS ) [ 104 – 106 ]. Hs-cTn assays also facilitate use of sexspeci ﬁ c $99^{\mathrm{th}}$ percentiles, recognising the differing trajectories of cTn in women and men across the life course [ 107 – 109 ].

Contemporary assays are still used in smaller hospitals around Australia, including point-of-care (POC) contemporary troponin assays in many regional and remote settings. Their lower sensitivity means they should be used in combination with clinical scores when risk stratifying people with suspected ACS (section 2.4 Risk Assessment and Clinical Decision Pathways for Suspected ACS ). POC hscTn assays have been developed and will likely become increasingly available [ 110 – 113 ].

2.3.1. Analytic properties of cardiac troponin assays

The cut-off or threshold used to de ﬁ ne an elevated cTn value which is diagnostic of myocardial injury is the $99^{\mathrm{th}}$ percentile of a healthy population and this value is assay-speci ﬁ c [ 15 ]. Within Australia, different units are used to report contemporary $(\upmu\mathrm{g/L})$ and high-sensitivity troponin assays (ng/L), re ﬂ ecting the lower sensitivity of the older assays ( Table 6 ). Other metrics of assay performance include limit of detection and limit of blank ( Figure 6 ).

Use of hs-cTn assays has shown that women have lower circulating normal cTn concentrations, resulting in sexspeci ﬁ c differences in the $99^{\mathrm{th}}$ percentile values between women and men [ 115 ]. Consequently, use of single overall cut-off points to determine myocardial injury and potentially MI in women will result in underdiagnosis [ 116 ].

In transgender women and men, the use of sex hormones, rather than sex assigned at birth, may impact on myocardial mass and in ﬂ uence hs-cTn reference ranges [ 117 ]. To maintain safety, the reference range should be based upon the lower cut-off points (female), however more research is required [ 117 ].

Table 6 Contemporary vs high-sensitivity cTn assay features.

|Characteristic|Contemporary troponin assays*|High-sensitivity troponin assays|| |---|---|---|---| |Precision|Variable|≤10% CV at 99thpercentile|| | Detection ~ 20-50% of healthy reference population|||| ||||| | Sex-specific 99th percentiles|No. Overall 99th percentile values only Yes. Female and male 9gth percentiles||| |Timing of serial testing for MI using| 0 and 6-8 hours |0 and 3 hours|| ||70||| | Single low-risk troponin values for MI* Ability to use in rapid, early assessment || Yes || | strategies|70|Yes|| | Platform||||

\*Using a contemporary assay, if a person presents symptom-free for ${>}6{-}8$ hours, only one test needed. If ${\leq}99^{\mathrm{th}}$ percentile at 6 – 8 hours, no second test is required. If ${\mathrm{>}}99^{\mathrm{th}}$ , a second test is needed. Abbreviations: cTn, cardiac troponin; CV, coef ﬁ cient of variation; MI, myocardial infarction; POC, point-of-care.

Despite observed increases in the $99^{\mathrm{th}}$ percentile of cTn in people aged over 60 years, changes to the $99^{\mathrm{th}}$ percentile based on age have not been implemented in clinical practice [ 115 , 118 – 120 ].

2.3.2. Point-of-care troponin assays

POC troponin assays may lead to more timely management of people with suspected ACS, with comparable safety to laboratory-based assays ( Table 7 in section 2.4.1.1 Highsensitivity troponin-based clinical decision pathways ) [ 110 , 111 , 113 , 121 ]. In comparison, use of contemporary POC assays requires serial measurements over 6 – 8 hours in people with suspected ACS [ 122 ].

Evaluations support rapid assessment using POC hs-cTn assays [ 110 , 111 , 113 , 123 ]. Knowledge of POC hs-cTn assays is rapidly evolving. Their use in clinical decision pathways in EDs, outpatient clinics and primary care may become more common given the clinical safety and cost ef ﬁ cacy of such assays [ 121 ].

2.3.3. Clinical interpretation of troponin values

cTn results must be carefully interpreted within the personspeci ﬁ c clinical context, including ECG ﬁ ndings ( Figure 7 ) [ 16 ]. Serial measurements are required to identify if there is a stable or changing pattern associated with an elevated cTn. Stable elevations are seen with chronic myocardial injury but may also be seen in the plateau phase of troponin release in MI (e.g. in people with delayed presentation). People with changing values (both increasing and decreasing) warrant evaluation for evidence of myocardial ischaemia. To note, acute myocardial injury due to other causes (e.g. acute heart failure, pulmonary embolism) needs to be considered when clinically appropriate. Differentiation between types of MI also requires careful evaluation, as does differentiation from myocardial injury ( Figure 7 ) [ 124 ].

The introduction of hs-cTn assays has led to a decrease in the frequency of UA, de ﬁ ned with cTn values ${\leq}99^{\mathrm{th}}$ percentile. Improved detection of small changes in troponin

![9gthpercentile,males 9gthpercentileclinical decisionvalues 99thpercentile,overall Malecut-offs>overallcut-offs>femalecut-offs 9gthpercentile,females Themeansignal atwhich5%of thefrequencydistributionis belowthelimitofblank(i.e.95%confidencethatcTnispresent Limitofdetection in the sample). 50/0 ](https://venus-trag-1258344701.cos-internal.ap-guangzhou.tencentcos.cn/userUpload/is-62e36cd9/2025-04-10/fb1c8c9f-efc2-4e33-bcfa-9162f5499f04/fb1c8c9f-efc2-4e33-bcfa-9162f5499f04.jpg?q-sign-algorithm=sha1&q-ak=AKID61g5D5fy1TjiRv84nEOHtFJ8gyzjCPL0&q-sign-time=1744240805%3B1744244405&q-key-time=1744240805%3B1744244405&q-header-list=host&q-url-param-list=&q-signature=aa1d78551c54228f479099e0d52b085f38e0318d) Figure 6 Various analytic de ﬁ nitions for troponin assays. Adapted with permission from Januzzi et al. [ 114 ]. Abbreviation: cTn, cardiac troponin.

Table 7 Troponin assay and metrics for use in 0/1- and 0/2-hour sampling strategies.

|Assay| Sampling timepoints ||B|||||| |---|---|---|---|---|---|---|---|---| |||||||| Female 99th percentile | Male 99th percentile | |Hs-cTnI (Architect; Abbott)|0/1h|人4|人5|人M|≥64|¥Z6| 16 |34| ||0/2h|人4|||||||

\*Point of care assay. $99^{\mathrm{th}}$ percentiles presented in column F/G are as per the International Federation of Clinical Chemistry tables rounded to the nearest whole number [ 40 , 42 , 105 , 123 , 148 , 151 , 153 – 155 , 169 , 170 , 176 – 185 ]. Abbreviations: hs-cTnI, high-sensitivity cardiac troponin I; hs-cTnT, high-sensitivity cardiac troponin T; NA, not available; TBD, to be determined.

levels has meant that a proportion of people previously classi ﬁ ed as UA have been reclassi ﬁ ed as MI [ 125 ].

2.3.4. Time from onset of coronary occlusion vs. symptom onset

In the setting of ACOMI, there may be a delay in elevation of cTn levels. However, this timeframe has become shorter with the ability of hs-cTn assays to detect lower concentrations of circulating troponin ( Figure 8 ). Repeat troponin testing is required for people with ongoing or recurrent symptoms or where there is a high suspicion of ACS.

2.3.5. Comparing results from different troponin assays cTn assays developed by various diagnostic companies use different antibody combinations, resulting in differences in numerical results for the same amount of circulating troponin. Signi ﬁ cant differences exist in the categorisation of people based on different hs-cTn assays [ 126 ]. Results of one assay cannot be interpreted using the reference range of a different assay. Serial testing of cTn concentrations can only be interpreted when measured using the same assay.

Differences between troponin T and I assays

Both high-sensitivity cardiac troponin I (hs-cTnI) and highsensitivity cardiac troponin T (hs-cTnT) provide comparable diagnostic accuracy in the early diagnosis of MI [ 127 ]. Troponin T is more likely to be elevated with poor renal

function (section 2.3.5 Comparing results from different troponin assays - Renal disease ) and chronic muscular diseases (e.g. chronic myopathy, myositis). This is possibly due to re-expression of cTnT in the diseased muscle or due to cross reactivity of the cTnT assay with a fragment of skeletal muscle troponin T [ 128 , 129 ].

Non-MI causes of troponin elevation

Numerous ischaemic, non-coronary cardiac, and non-cardiac causes of myocardial injury can result in elevated cTn concentrations ( Figure 9 ) [ 15 , 102 , 130 , 131 ]. Life-threatening conditions including aortic dissection and pulmonary embolism may result in elevated cTn values. Cardiac troponin elevation indicates myocardial injury but is not speci ﬁ c to the underlying pathophysiology [ 15 ].

Renal disease

Chronically elevated cTn concentrations are often reported with decreased renal function, more so with cTnT than cTnI. Published guidelines for MI diagnosis in people undergoing haemodialysis recommend serial cTn measurements, rather than management according to an elevated baseline value [ 132 ].

False positive and false negative cardiac troponin results Analytically false positive and false negative cTn results are uncommon. False positive results for cTn may occur due to

![Clinical interpretation of high-sensitivity cardiac troponin Serial testing forsuspected Acs If any elevated troponin value -increased above upper reference limit:>9gth sex-specific percentile Step 1: Identify significant change in serial testing? yes NO Troponinlevel stable Step2:Identifyevidenceofacutemyocardialischaemia? Myocardial infarction Yes 20 Step3:Identifycauseofmyocardialischaemia? Evidence of acute Clinical context and coronaryocclusion mechanisms for oxygen demand and supply imbalancewithout coronaryocclusion MI with acute coronary MI due to oxygen Acutemyocardial Chronic myocardial occlusion supply/demand injury injury mismatchwithout acute Examples Examples Examples coronaryocclusion ·Plaquerupture/erosion ·Acute heart failure Structuralheartdisease SCAD Examples ·Myocarditis ·Chronic kidney disease Coronaryembolism Withfixedobstructive Vasospasm/ CAD microvascular Without fixed obstructive dysfunction CAD ](https://venus-llm-1258344701.cos-internal.ap-guangzhou.tencentcos.cn/userUpload/is-62e36cd9/2025-04-10/e99cbaf5-411a-4657-b1a2-b075d5e16d04/e99cbaf5-411a-4657-b1a2-b075d5e16d04.jpg?q-sign-algorithm=sha1&q-ak=AKID61g5D5fy1TjiRv84nEOHtFJ8gyzjCPL0&q-sign-time=1744240805%3B1744244405&q-key-time=1744240805%3B1744244405&q-header-list=host&q-url-param-list=&q-signature=93a229850008204c6c5484b9d8aadee2472c823c) Figure 7 Clinical interpretation of high-sensitivity cardiac troponin (hs-cTn) results. Adapted with permission from the Accelerated Chest Pain Risk Evaluation (ACRE) Project, Clinical Excellence Queensland, Queensland Health. For guidance on identifying evidence for acute myocardial ischaemia, refer to sections 2.2.2 High-risk ECG ﬁ ndings and 2.2.3 Other signs of myocardial ischaemia on ECG .

Abbreviations: ACS, acute coronary syndromes; CAD, coronary artery disease; MI, myocardial infarction; SCAD, spontaneous coronary artery dissection.

antibody interference from macrotroponins. Macrotroponins are high-molecular weight complexes of cTn fragments that bind to immunoglobulins (cTn autoantibodies) causing delayed troponin clearance. In addition, heterophilic antibodies can bind to cTn assay antibodies, causing positive signals in the absence of cTn. The causes of heterophilic antibodies are largely unknown, however they may be found in people with rheumatoid arthritis, and viral infections such as Epstein Barr virus and cytomegalovirus [ 133 ]. Conversely,

severe haemolysis and other substances in plasma, like biotin, may result in false negative results [ 134 , 135 ].

When cTn results and the clinical presentation are discordant, the hospital ’ s laboratory should be contacted to exclude rare false positive cTn results [ 134 ].

Other biomarkers

Additional biomarkers exist but are not used to diagnose MI. There is no role for creatine kinase MB-isoenzyme (CK-MB), including in identifying reinfarction in people with AMI [ 136 ].

2.4. Risk Assessment and Clinical Decision Pathways for Suspected ACS

Recommendations

|Recommendation| Strength of recommendation | Certainty of evidence | |---|---|---| ||Strong|| | People with symptoms||VeryLow| |and ECG changes||| |consistent with ACOMI||| |require urgent||| |reperfusion. Do not use||| | clinical decision pathway||| |||| | People presenting with|| Consensus| |acute chest pain or other||| |symptoms suggestive of||| |ACS should receive care||| |guided by an evidence-||| |based CDP that includes||| | assay-specific troponin||| |results to categorise||| |people as high,||| |intermediate, or low risk.||| |A high-sensitivity|Consensus|| | troponin-based clinical||| |decision pathway is||| |recommended, using the||| |0/1-hour or 0/2-hour||| |strategy, or the High-||| |sensitioity troponin in the||| |evaluation of patients with||| |acute coronary syndrome||| |(High-STEACS) algorithm.||| |||| |When contemporary|Consensus|| |troponin assays are used, a||| | CDP incorporating formal clinical score-based risk ||| | stratification is||| | recommended.|||

Evidence supporting the recommendations

For people with suspected ACS, a clinical decision pathway improves care and health service ef ﬁ ciency. The aim is to identify people with MI and those at high risk of MACE within 30 days. The latter may require further investigation or longer periods of observation before discharge [ 137 ]. A de ﬁ ned process also reduces unnecessary investigations and treatment and decreases avoidable inpatient admissions for people at low risk of 30-day MACE. Evidence suggests missed MI and/or 30-day MACE rates of ${<}1\%$ in people discharged from the ED following structured

risk assessment incorporating clinical information, cTn and ECG ﬁ ndings [ 39 , 138 – 140 ].

People with ECGs suggestive of ischaemia, including those at high risk of progressing to ACOMI, should receive inpatient evaluation (section 2.2 Initial ECG Assessment ).

Various clinical decision pathways are available for people in whom ACOMI is initially excluded and in the absence of ischaemic ECG ﬁ ndings. Some pathways focus on optimum use of hs-cTn results alone (section 2.4.1.1 High-sensitivity troponin-based clinical decision pathways ), while others use a clinical risk scoring system incorporating contemporary cTn values (section 2.4.1.2 Clinical score-based clinical decision pathways ). Examples of the latter include the Emergency department assessment of chest pain score (EDACS) and the History, ECG, age, risk factors and troponin (HEART) score (section 2.4.1.2 Clinical score-based clinical decision pathways and Supplementary Material B2 ) [ 141 ].

2.4.1. Clinical decision pathways Risk strati ﬁ cation

A three-tiered strati ﬁ cation is recommended, grouping people into high, intermediate, or low risk of MACE including MI ( Figure 10 ). In addition to cTn measurement, all approaches incorporate history and physical examination ﬁ ndings, and ECG results (normal, non-ischaemic, or unchanged from previously).

' High risk : the probability of an event, most commonly MI, within 30 days is higher than $50–70\%$ (positive predictive value ${>}50\%{-}70\%$ ) [ 142 ]. These people require admission and further evaluation.

Importantly, not all high-risk people are ultimately determined to have an MI. Clear communication about risk of MI is essential. Refer to section 3 Hospital Care and Reperfusion for further evaluation and management of high-risk people.

' Intermediate risk : for people identi ﬁ ed as intermediate risk using the hs-cTn-based CDP (0/1 or 0/2-hour strategies), 30-day MACE rates vary between $2–22\%$ . These people require further evaluation [ 42 , 143 , 144 ]. Intermediate-risk people will have either normal $({\leq}99^{\mathrm{th}}$ percentile) or elevated $(>\!99^{\mathrm{th}}$ percentile) cTn values, with the latter requiring evaluation in an inpatient setting. For intermediate-risk people with serial cTn results $\mathord{\le}99^{\mathrm{th}}$ percentile, outpatient testing is acceptable as the 30-day MACE rate in this group is ${<}2\%$ (section 2.6 Further Diagnostic Testing for People with Suspected ACS ) [ 39 ]. People with elevated but unchanging cTn values consistent with chronic myocardial injury are out of the scope of this guideline (section 2.3 Biomarkers ). However, it is important to note these people have an elevated risk of future cardiac events than those without myocardial injury [ 15 , 145 ].

' Low risk : the risk of MACE within 30 days is ${<}1\%$ using either a hs-cTn-based CDP or a clinical risk score-based CDP ( Table 7 and Supplementary Material B2 ). In general, hs-cTn strategies safely de ﬁ ne a larger proportion of people as low-risk than clinical risk score pathways that

![Acute myocardial infarction Chronic myocardial injury 99thpercentileURL Veryearly Early Later Verylate sampling sampling sampling sampling Time from onset of symptoms (hours) ](https://venus-llm-1258344701.cos-internal.ap-guangzhou.tencentcos.cn/userUpload/is-62e36cd9/2025-04-10/2953c067-7021-4a92-b14f-9fffbfe5dd3a/2953c067-7021-4a92-b14f-9fffbfe5dd3a.jpg?q-sign-algorithm=sha1&q-ak=AKID61g5D5fy1TjiRv84nEOHtFJ8gyzjCPL0&q-sign-time=1744240805%3B1744244405&q-key-time=1744240805%3B1744244405&q-header-list=host&q-url-param-list=&q-signature=7317505e5ad65fce3c73e61e192b9ccb4f187446) Figure 8 Early troponin kinetics in people with acute myocardial infarction. Abbreviations: cTn, cardiac troponin; URL, upper reference limit.

use contemporary cTn assays. When de ﬁ ned as low-risk using a hs-cTn strategy, further testing to exclude AMI is not required [ 16 , 146 , 147 ].

Risk strati ﬁ cation for people with suspected ACS: identifying myocardial infarction and unstable angina For people without ﬁ ndings consistent with ACOMI on the initial ECG, further assessment aims to identify NSTEMI and UA through evaluation of clinical features with additional ECG and troponin testing. NSTEMI is associated with elevated cTn values.

People with ongoing or recurrent ischaemic symptoms, or new ECG ﬁ ndings suggestive of ischaemia during initial or repeat testing, should be considered high risk for ACS. Serial cTn testing should be pursued if clinical suspicion of ACS remains high, as late increases in cTn have been described in ${<}1\%$ of people with NSTEMI [ 148 ].

2.4.1.1. High-sensitivity troponin-based clinical decision pathways

Strategies incorporating hs-cTn assay results rather than contemporary troponin assays are recommended for safe, rapid decision making. Overall, hs-cTn-based risk strati ﬁ cation identi ﬁ es $\sim\!50{-}65\%$ of people presenting with suspected ACS as low risk, ${\sim}20–30\%$ as intermediate risk and

${\sim}15{-}25\%$ as high risk for MACE [ 149 , 150 ]. When used in a validated algorithm combined with non-ischaemic ECG changes, safety and ef ﬁ cacy are achieved without using clinical risk scores [ 16 , 142 ].

$0\mathrm{-},\,0/1\mathrm{-},$ and 0/2-hour strategies have been developed for most hs-cTn assays and the values are assay-speci ﬁ c ( Figure 11 , Table 7 and Supplementary Material B1 ) [ 42 , 106 , 142 , 143 , 148 , 151 – 158 ].

Single high-sensitivity cardiac troponin measurements

A single hs-cTn measurement is not suitable for people with symptom onset ${<}2$ hours. These people require serial testing [ 23 , 106 , 143 , 153 , 155 , 159 – 161 ]. In people with symptom onset ${\geq}2$ hours, combining a single hs-cTn result with non-ischaemic ECG ﬁ ndings can very safely identify $20–50\%$ of people as low risk [ 42 , 46 , 105 , 106 , 143 , 147 , 149 – 152 , 155 , 161 – 168 ].

A single measurement approach has been extensively validated using both hs-cTnT and hs-cTnI assays, with high negative predictive value and sensitivity for excluding index MI and a ${<}1\%$ risk of MACE during short- and longer-term follow-up [ 40 , 104 , 105 , 147 , 149 , 161 , 168 – 171 ]. Unlike hs-cTn assays, using a single contemporary troponin measurement to assess risk has not been validated [ 172 ].

|Clinical manifestation|Possible causesofelevation| Possible mechanism Necrosis Apoptosis and necroptosis Reversible troponin leakage (cell stretching, cell wounds, bleb formation) ||| |---|---|---|---|---| |ANI|ANI| Possible mechanism Necrosis Apoptosis and necroptosis Reversible troponin leakage (cell stretching, cell wounds, bleb formation) | Prolonged ischaemia| Prolonged ischaemia| |Acute HF|Acute HF| Possible mechanism Necrosis Apoptosis and necroptosis Reversible troponin leakage (cell stretching, cell wounds, bleb formation) | Prolonged ischaemia| Prolonged ischaemia| | Pulmonary embolism| Pulmonary embolism| Possible mechanism Necrosis Apoptosis and necroptosis Reversible troponin leakage (cell stretching, cell wounds, bleb formation) | Prolonged ischaemia| Prolonged ischaemia| |Chest trauma or surgery| Mechanical cell destruction, local inflammation | Possible mechanism Necrosis Apoptosis and necroptosis Reversible troponin leakage (cell stretching, cell wounds, bleb formation) ||| |Stroke or brain trauma| Catecholamine-derived myocyte overload or ischaemia due to type 2 MI | Possible mechanism Necrosis Apoptosis and necroptosis Reversible troponin leakage (cell stretching, cell wounds, bleb formation) ||| |Cardiotoxicity|Cardiotoxicity| Possible mechanism Necrosis Apoptosis and necroptosis Reversible troponin leakage (cell stretching, cell wounds, bleb formation) |Cardiotoxic agents (drugs, CO, poisons)|| |Myocarditis, endocarditis|Inflammation|Inflammation||| |Sepsis|Sepsis|Inflammation||| |Atrial fibrillation|Atrial fibrillation| Possible mechanism Necrosis Apoptosis and necroptosis Reversible troponin leakage (cell stretching, cell wounds, bleb formation) | Brief ischaemia Muscle overload || |Chronic HF|Chronic HF| Possible mechanism Necrosis Apoptosis and necroptosis Reversible troponin leakage (cell stretching, cell wounds, bleb formation) | Brief ischaemia Muscle overload || |Chronic HF|Chronic HF| Possible mechanism Necrosis Apoptosis and necroptosis Reversible troponin leakage (cell stretching, cell wounds, bleb formation) | Brief ischaemia Muscle overload || |StableCAD|StableCAD| Possible mechanism Necrosis Apoptosis and necroptosis Reversible troponin leakage (cell stretching, cell wounds, bleb formation) | Brief ischaemia Muscle overload || |Physical exercise|Physical exercise| Possible mechanism Necrosis Apoptosis and necroptosis Reversible troponin leakage (cell stretching, cell wounds, bleb formation) | Brief ischaemia Muscle overload || |Renal failure|Renal failure| Possible mechanism Necrosis Apoptosis and necroptosis Reversible troponin leakage (cell stretching, cell wounds, bleb formation) |Impaired clearance|Impaired clearance| |Skeletal muscle disorders| Expression of cTnT in regenerative skeletal muscles | Possible mechanism Necrosis Apoptosis and necroptosis Reversible troponin leakage (cell stretching, cell wounds, bleb formation) |||

Figure 9 Conditions associated with troponin elevation. Adapted from Katrukha et al. [ 102 ].

Abbreviations: AMI, acute myocardial infarction; CAD, coronary artery disease; CO, carbon monoxide; cTnT, cardiac

troponin T; HF, heart failure; MI, myocardial infarction.

0/1-, and 0/2-hour strategies

For people identi ﬁ ed as being at intermediate risk using the 0/1- or 0/2-hour strategies, index or 30-day MACE rates may vary between $2–22\%$ , and additional evaluation is required (section 2.6 Further Diagnostic Testing for People with Suspected ACS ) [ 42 , 143 , 144 ]. For people with normal serial cTn values, 30-day MACE rates are ${\leq}2\%$ [ 39 ].

While mostly large observational studies have evaluated 0/1- and 0/2-hour strategies, randomised trials of the 0/1-hour strategy have reported 30-day MI and death rates of ${<}1\%$ [ 42 , 154 , 173 – 175 ]. In addition to values being assay dependent, the change thresholds (deltas) for the 0/1- and 0/ 2-hour algorithms are time dependent. This means it is crucial that blood specimens are collected within the speciﬁ ed windows ( Table 7 ).

In most hospitals, delays in central laboratory assay turnaround times render the 0/1-hour strategy impractical. POC hs-cTn assays may overcome this limitation but are not yet widely available. A 0/2-hour strategy is therefore currently the most practical option in most settings.

High-STEACS algorithm

The United Kingdom (UK) High-STEACS algorithm is a wellvalidated, safe and effective approach using a variety of hs

cTn assays [ 40 , 147 , 150 , 154 , 160 ]. Further details are described in the Supplementary Material B1 .

2.4.1.2. Clinical score-based clinical decision pathways Sites using contemporary cTn assays

Incorporation of a clinical score-based tool (e.g. EDACS, HEART) in assessing people with suspected ACS is essential if using a contemporary cTn assay. EDACS and the HEART score are the most widely validated strategies and have high sensitivity for index AMI and 30-day MACE (see Supplementary Material B2 ) [ 163 , 165 , 186 – 194 ]. However, when compared to hs-cTn-based CDP, smaller numbers of people will be identi ﬁ ed as low/intermediate risk and additional testing may occur without an improvement in MACE [ 42 , 46 , 106 , 151 , 152 , 166 , 167 , 172 , 178 , 195 , 196 ]. Furthermore, because sex-speci ﬁ c considerations are not included in all scoring systems, their effectiveness in men and women may not be equal [ 197 ]. Further information on these clinical based scores is provided in the Supplementary Material B2 .

2.4.2. Implementing a clinical decision pathway for suspected ACS

Implementation of CDPs for suspected ACS, especially CDPs using hs-cTn assays rather than clinical risk scores, confers

![PresentationconsistentwithsuspectedACS Perform12-leadECG ECGfindingsofACOMIor Yes Manageaccordingto high-risk ECG findings Section3Hospitalcare (Section 2.2) andreperfusion 20 LowriskforAMland UseCDP 30-dayMACE High-sensitivitytroponin-based CDP (Section 2.4.1.1) IntermediateriskforAMI and 30-day MACE Cr Clinicalriskscore-basedCDP (Section 2.4.1.2) HighriskforAMl and 30-dayMACE ](https://venus-llm-1258344701.cos-internal.ap-guangzhou.tencentcos.cn/userUpload/is-62e36cd9/2025-04-10/1cb43eaa-26fc-4d6c-9a75-f7a9f59f5437/1cb43eaa-26fc-4d6c-9a75-f7a9f59f5437.jpg?q-sign-algorithm=sha1&q-ak=AKID61g5D5fy1TjiRv84nEOHtFJ8gyzjCPL0&q-sign-time=1744240805%3B1744244405&q-key-time=1744240805%3B1744244405&q-header-list=host&q-url-param-list=&q-signature=857550d779a2e5ccde03cf32e373190f3555437a) Figure 10 Assessment process for people with suspected ACS. Abbreviations: ACOMI, acute coronary occlusion myocardial infarction; ACS, acute coronary syndromes; AMI, acute myocardial infarction; CDP, clinical decision pathway; ECG, electrocardiogram; MACE, major adverse cardiovascular events.

signi ﬁ cant bene ﬁ ts for people and health care systems, and requires the engagement of multidisciplinary teams [ 23 , 39 , 146 , 175 , 189 , 190 , 198 – 202 ].

In an Australian randomised controlled trial (RCT) using hs-cTnT, the 0/1-hour strategy resulted in more frequent ED discharge ( $45\%$ vs $32\%$ ; $\mathtt{p}<\!0.001)$ and a reduced ED length of stay $(\mathfrak{p}^{<0.001})$ ). Similar clinical outcomes occurred at 30 days $\scriptstyle(\mathtt{p}=0.001$ for noninferiority) compared with a usual care approach using 0/3-hour cTn measurements with an hs-cTnT threshold of ${\ge}30\,\mathrm{\ns/L}$ [ 173 ]. A large, randomised trial showed failure to follow recommended management for low-risk people resulted in substantial increases in resource use with no differences in 30-day MACE [ 146 ].

Centres choosing to implement an alternate strategy to the recommended CDPs should validate this CDP. Validation should include assessment of 30-day mortality and representation with con ﬁ rmed ACS in all people with chest pain.

Practice points

Women

' Apply sex-speci ﬁ c $99^{\mathrm{th}}$ percentile upper reference limit when using hs-cTn assays ( Figure 11 ) [ 15 , 40 , 42 , 116 , 156 , 203 ]. B Women are frequently misdiagnosed with having nonischaemic chest pain, and their ACS risk is often underestimated [ 41 , 45 , 197 , 204 , 205 ]. This is due in part

to traditional risk tools lacking sex-speci ﬁ c considerations and clinician bias.

Older adults

' Use uniform hs-cTn cut-offs for clinical assessment, recognising that concentrations increase with age in healthy people. This may result in fewer older adults being deemed at low risk for MI [ 15 ]. B In older people $({\geq}65$ years) with comorbidities such as renal impairment, the speci ﬁ city of hs-cTn results for MI is reduced [ 179 , 203 , 206 , 207 ].

First Nations peoples

' Use a single hs-cTn measurement in First Nations peoples to identify people as low risk of MI and 30-day MACE [ 208 ]. ' Be cautious of implementing the HEART score and IMPACT pathways, which have been evaluated in small studies in First Nations populations (see Supplementary Material B2 ) [ 209 ]. ' Investigate all First Nations adults (18 years and over) with suspected ACS for underlying CAD, given their high risk of future cardiac events [ 210 , 211 ].

People with renal impairment

' Use hs-cTn-based strategies in people with renal dysfunction, noting that fewer individuals will be classiﬁ ed as low risk compared to other approaches [ 206 , 207 ].

![PresentationconsistentwithsuspectedAcs and Normal ECG or absence of ECG patterns associated with ACO or high-risk ECG features O-hour<A# Otherresults O-hour>D# or 0-hour<B#and△0/2-hour<C# △ 0/2-hour >E# \*Onset of symptoms ≥2 hours LOWrisk INTERMEDIATErisk HIGH risk Bothvalues Eithervalue ≤ sex-specific > sex-specific 99th percentile 99th percentile Discharge Further evaluation of long- Admitforfurther termriskasperAustralian evaluationandtreatment CVDRiskGuideline Further testing asoutpatient recommended Footnote:AdaptationforserialsamplingneededforO/1-hourstrategy. ](https://venus-trag-1258344701.cos-internal.ap-guangzhou.tencentcos.cn/userUpload/is-62e36cd9/2025-04-10/a95bfd7c-dc22-49dd-a9a6-67f1250f8c33/a95bfd7c-dc22-49dd-a9a6-67f1250f8c33.jpg?q-sign-algorithm=sha1&q-ak=AKID61g5D5fy1TjiRv84nEOHtFJ8gyzjCPL0&q-sign-time=1744240805%3B1744244405&q-key-time=1744240805%3B1744244405&q-header-list=host&q-url-param-list=&q-signature=4a9f89ddb5fbb97eeaffd5a938df76aebc6cf385) Figure 11 0/2-hour testing recommendations. Note: the 0/2-hour time points are shown in this ﬁ gure. If using a 0/1-hour strategy, change timeframes accordingly. # Refer to Table 7 for interpretation of cTn assay-speci ﬁ c values and sex-speci ﬁ c $99^{\mathrm{th}}$ percentiles. \*All people with symptom onset ${<}2$ hours need serial testing. People with ongoing symptoms should be assessed according to high-risk criteria. Abbreviations: ACO, acute coronary occlusion; ACS, acute coronary syndromes; cTn, cardiac troponin; ECG, electrocardiogram.

B Elevations in cTn are common in this population, leading to their exclusion from many assessment trials [ 212 ]. The safety of hs-cTn-based strategies appears to be similar in people with and without renal dysfunction.

2.4.3. Future direction

Newer strategies for individualised determination of likelihood of MI

Newer strategies to determine risk of MI have been developed based on large international datasets using machine learning techniques. These include the $\mathrm{MI}^{3}$ algorithm study (derived in 3,013 people and validated in 7,998 people), the ARTEMIS study (derived in 2,575 people and validated in 23,411 people) and the CoDEACS study (derived in 10,038 people and externally validated in 3,035 people) [ 213 – 215 ]. Such strategies use additional information (e.g. speci ﬁ c interval time of cTn testing, biometric measurements). Validation studies suggest large proportions of people can be de ﬁ ned as low risk, with improved speci ﬁ city for MI in high-risk people.

2.5. Initial Therapeutic Management

Recommendations

|Recommendation|Strength of|Certainty of| |---|---|---| ||recommendation evidence|| | In all people with suspected |dStrong|High| |or confirmed ACS, give||| |aspirin (300 mg orally,||| |dissolved or chewed) unless||| |contraindicated.||| |||| |People with suspected or| Strong|Moderate| |confirmed ACS with oxygen||| |saturation (SpO2) ≥90% do||| |not require oxygen therapy.||| |In people with suspected or|Strong|Moderate| | confirmed ACS receiving||| | oxygen therapy, SpO2||| |should not exceed 96%.|||

|(continued).||| |---|---|---| |Recommendation| Strength of Certainty of recommendation1evidence || | In the presence of ongoing|Consensus|| |chest pain, give glyceryl||| | trinitrate sublingual tablet or||| | spray every 5 minutes for up||| |to three doses if no||| | contraindications exist.||| |||| | In people with chest pain|Consensus|| |and in the absence of||| | contraindications, it is||| |reasonable to administer||| | intravenous (IV) fentanyl or||| | morphine boluses.|||

Evidence supporting the recommendations

Aspirin

Large meta-analyses have con ﬁ rmed that the bene ﬁ ts of aspirin in reducing the risk of serious vascular events (vascular death, MI and stroke) in people with known ASCVD outweigh the small increased risk of major bleeding [ 216 , 217 ]. Although maintenance doses of $100\,\mathrm{\mg}$ are as effective as larger doses, a loading dose of $300~\mathrm{mg}$ is recommended. This is based on pharmacokinetic data showing that a larger loading dose is required to completely inhibit the thromboxane mediated pathway of platelet activation (section 3.4 Antiplatelet Therapy in the Acute Phase ) [ 218 ].

Oxygen therapy

Two large pragmatic randomised trials have shown that the routine use of supplemental oxygen in people with suspected ACS without hypoxaemia does not improve mortality at 30 days or 12 months [ 219 , 220 ]. In addition, a meta-analysis incorporating one of these and several earlier smaller studies has found that oxygen therapy is associated with a greater incidence of recurrent MI and coronary revascularisation at 6 – 12 months. This study also reported evidence of a dose response relationship between oxygen saturation and increased mortality in acutely ill people and people in intensive care, including those with MI. Thus, caution against achieving higher saturations in these groups is advised [ 221 ].

Practice points

Oxygen therapy

' Provide oxygen therapy routinely if oxygen saturation falls below $90\%,$ , as hypoxaemia at this level is assumed to contribute to coronary ischaemia. The clinical outcome bene ﬁ ts remain uncertain [ 219 ]. ' Recognise that oxygen therapy is commonly administered when oxygen saturation is between $90–92\%,$ although its bene ﬁ t is unknown [ 222 – 224 ]. ' Exercise caution people with chronic obstructive pulmonary disease (COPD) when administering supplemental

oxygen, aiming for a target arterial oxygen saturation (SaO2) of approximately $88–92\%$ .

Nitrates

' Use IV glyceryl trinitrate for more effective symptom relief in acute ischaemia compared to the sublingual form, but be aware that it does not alter prognosis [ 225 , 226 ]. ' Do not administer glyceryl trinitrate in cases of hypotension, right ventricular infarction, or recent use of a phosphodiesterase 5 inhibitor (sildena ﬁ l, vardena ﬁ l or tadala ﬁ l). Consider alternative therapy if symptoms persist.

Opioid analgesia

' Titrate doses of opioid analgesia to resolution of chest pain, adjusting for individual needs based on age, comorbidities, and concurrent medicine use [ 227 – 229 ]. ' Consider fentanyl for its short time to peak effect, short duration of action, and minimal impact on histamine release. B Note that both morphine and fentanyl are associated with increased platelet reactivity, reduced antiplatelet effect of $\mathrm{P}2\mathrm{Y}_{12}$ inhibitors and slower absorption of oral medicines such as ticagrelor during the early hours of ACS [ 228 , 230 – 232 ].

Other medicines

' Do not administer non-steroidal anti-in ﬂ ammatory medicines (NSAIDS) in con ﬁ rmed ACS, especially in the early phase, due to the increased risk of MACE [ 233 , 234 ]. ' Do not initiate additional antiplatelet, anticoagulation or beta blocker therapies without a con ﬁ rmed or probable diagnosis of ACS (section 3.4 Antiplatelet Therapy in the Acute Phase and 3.5 Anticoagulant Therapy in the Acute Phase ).

2.6. Further Diagnostic Testing for People with Suspected ACS

Recommendations

|Recommendation| Strength of recommendation ||Certainty| |---|---|---|---| |Recommendation| Strength of recommendation || O1 evidence | ||||| | In people at intermediate risk||Strong|Moderate| |(as defined by a validated|||| |CDP) with elevated troponin|||| |concentrations (>99th|||| | percentile), inpatient|||| | investigation is recommended.|||| | In people at intermediate risk||Consensus|| |without elevated troponin|||| | concentrations, consider|||| | outpatient investigation with|||| | non-invasive testing.|||| ||||| | In people at low risk who||Consensus|| | remain symptom-free, further|||| |cardiac testing for CAD is not|||| |routinely required.||||

Evidence supporting the recommendations

In people at intermediate risk of ACS, invasive angiography or non-invasive cardiac testing allows further risk strati ﬁ cation. These tests may also help establish alternative aetiology of chest pain and future risk of ACS beyond 30 days.

Invasive or non-invasive inpatient testing is recommended for people at intermediate risk with elevated hs-cTn concentrations above the sex-speci ﬁ c $99^{\mathrm{th}}$ percentile ( Figure 11 ) because of the relatively high rate of a cardiac event within 30 days $(2{-}22\%,$ , section 2.4 Risk Assessment and Clinical Decision Pathways for Suspected ACS ) [ 235 , 236 ].

Outpatient non-invasive testing can be considered (ideally within 30 days) for people at intermediate risk with serial

values ${\leq}99^{\mathrm{th}}$ percentile, in whom the 30-day event rate is substantially lower $(<\!2\%)$ [ 39 ].

Non-invasivetestingis notroutinelyrecommendedinpeople classi ﬁ ed as low risk. The criteria used to de ﬁ ne low-risk people in whom further investigation is not warranted have varied [ 16 , 146 , 147 , 237 , 238 ]. In people strati ﬁ ed as low risk using CDPs recommended in this guideline (section 2.4 Risk Assessment and Clinical Decision Pathways for Suspected ACS ) the likelihood of a cardiac event over the next 2 years is low. Further cardiac anatomic or functional investigations are unnecessary, at least in the short term [ 42 , 110 , 149 , 160 , 169 , 239 ].

General practitioner follow-up is recommended to ensure resolution and appropriate treatment of the presenting

Table 8 Clinical considerations for the use of non-invasive testing for people at intermediate risk. Adapted with permission from Kontos et al. [ 246 ].

| Ischaemic test modality | Strengths|Considerations for use|| |---|---|---|---| ||·Low cost|● Decreased accuracy compared|| |Exercise stress ECG|● Wide availability|with anatomical and|· Rarely recommended as a| ||● Assessment of exercise|stress-imaging tests| stand-alone test in people| || symptoms, capacity|● Requires interpretable ECG| with known CAD, inability to exercise, or significant | ||● No ionising radiation| and ability to exercise sufficiently|| ||||arrhythmias| ||| ● Higher false positive rate in females | · Contraindicated in severe symptomatic aortic stenosis | |||| or severe hypertension| |Stress|● Wide availability|● Decreased sensitivity compared|| |echocardiography|● High diagnostic specificity|with anatomical and other| · Known good image quality and ability to exercise | |echocardiography|● Assessment of ventricular|stress-imaging tests| Consider use of an ultrasound-| || and valvular function|· Dependent on good image quality|enhancing agent to improve| ||● No ionising radiation| ·● Requires dobutamine in people unable to exercise |endocardial visualisation| |||| ● Known moderate or severe valvular disease | ||● Wide availability|· Increased artefacts resulting|· Known CAD or high coronary| |Stress/rest SPECT| ● Relatively high diagnostic sensitivity | in non-diagnostic results| artery calcification burden on| |Stress/rest SPECT||and decreased diagnostic|chest computed tomography| || · Assessment of ventricular function | accuracy compared with|(CT) imaging| || · Assessment of ventricular function ||● Preferred over stress| |||| echocardiography in people who| ||||cannot exercise or who have| |||| significant exercise-induced| |||| bronchospasm | |Stress/rest PET|● High diagnostic accuracy|● Limited availability|· Known CAD or high coronary| || ● Lower radiation exposure than SPECT |· Relatively higher cost| artery calcification burden on| || than SPECT ● Measures myocardial blood |● Lack of exercise assessment |chest CT imaging| |||● Lack of exercise assessment |● Preferred over SPECT due to| ||flow and flow reserve||higher diagnostic accuracy| ||· Assessment of ventricular|| and lower rate of nondiagnostic| ||function||test results|

Table 8. (continued).

| Ischaemic test modality |Strengths|Limitations|| Considerations for use| |---|---|---|---|---| | Stress CMR|● High diagnostic accuracy|● Limited availability||● Known CAD and/or| ||· Accurate assessment of||· Relatively higher cost|cardiomyopathy| ||chamber sizes, ventricular||· Lack of exercise assessment|● Elevated troponin not thought| ||and valvular function||· Long scan acquisition times|to be secondary to ACS| |||● Diagnosis of prior infarction,|· Claustrophobia|● Known moderate or severe| || scar, fibrosis||· Often not immediately|valvular disease| |||· Measurement of myocardial| available to people with pacemakers or ICDs |· No significant renal dysfunction| |||blood flow and flow reserve||| ||| is possible (but not Contraindicated in people with significant renal dysfunction ||| |||widely available currently)||| ||· No ionising radiation|||| |· High diagnostic accuracy| · Radiation exposure ● Lack of exercise assessment ||● No known CAD|| |● Does not require exercise|||· Absence of severe coronary|| |● Identifies non-obstructive|| 0 Contraindicated in people with significant renal dysfunction |calcification|| |||| · Prior normal, mildly abnormal, or inconclusive stress test results || || Blooming artefacts when significant coronary calcification present ||· No known iodinated contrast|| ||||| medium allergy or significant| |||● Atrial fibrillation or other||renal dysfunction| |||· May require beta blockers||● Low likelihood of high-quality| |||||stress testing or lack of| |||● Incidental non-cardiac findings||timely access|

Abbreviations: ACS, acute coronary syndromes; ECG, electrocardiogram; CAD, coronary artery disease; CMR, cardiac magnetic resonance imaging; CT, computed tomography; CTCA, CT coronary angiogram; ICD, implantable cardioverter de ﬁ brillator; PET, positron emission tomography; SPECT, single photon emission computed tomography.

symptoms. If appropriate, the person ’ s long-term risk of a cardiovascular event should be assessed as per the Australian guideline for assessing and managing cardiovascular disease risk ( cvdcheck.org.au ).

Practice points

Non-invasive test selection – anatomical versus functional Anatomical testing (CTCA)

' Use computed tomography coronary angiography (CTCA) as a ﬁ rst-line investigation for people without previously known CAD presenting with intermediate-risk ACS, if no contraindications exist ( Table 8 ). ' Consider functional testing with close monitoring and a graduated exercise regime for people with contraindications to CTCA. ' Recognise that a normal CTCA (ruling out both obstructive and non-obstructive plaque) reliably excludes ACS and indicates an extremely low risk of ACS for at least 4 – 5 years [ 240 – 245 ]. Identifying non-obstructive plaque on CTCA can guide preventative therapies, such as lipidlowering treatment. ' Do not rely on coronary artery calcium scoring alone in ACS evaluation unless combined with CTCA. Functional testing ' Favour functional testing for people with known CAD, prior stents or extensive coronary calci ﬁ cation, where CTCA interpretation may be more challenging. Functional tests can help identify whether symptoms are caused by obstructive plaque and assess ischaemic burden and shortterm prognosis. ' Select functional tests based on clinical needs, including stress echocardiography, stress cardiac MRI, stress/rest single-photon emission computed tomography (SPECT), stress/rest positron emission tomography (PET), or exercise ECG ( Table 8 ). ' Recognise the additional diagnostic bene ﬁ ts of stress cardiac MRI and echocardiography, such as evaluating left ventricular function, regional wall motion abnormalities and valvular function, and excluding differential diagnoses like myopericarditis and Takotsubo cardiomyopathy.

Considerations for test selection

' Consider individual cardiovascular risk factors, local expertise and the availability of health services, particularly in regional and remote areas, when selecting non-invasive cardiac investigations as these all may inﬂ uence the selection [ 16 , 246 – 248 ].

' Prioritise inpatient non-invasive testing for low-risk individuals with factors limiting access to timely follow-up or the ability to re-present to ED, such as First Nations peoples with suspected ACS or those facing sociodemographic challenges [ 210 ].

2.6.1. Cost-effectiveness

Reducing unnecessary testing has bene ﬁ ts for both people and health services, including cost bene ﬁ ts. One Australian study estimated a total cost saving of $\S13.5$ million per annum after implementation of an accelerated diagnostic pathway that reduced hospital admission rates and ED length of stay [ 190 ].

2.6.2. Considerations for regional, remote and First Nations peoples

Regional, remote and First Nations peoples are disproportionately affected by reduced access to services, longer wait times and greater travel distances to access diagnostic services. De ﬁ nitive early identi ﬁ cation of CAD using CTCA may be of signi ﬁ cant bene ﬁ t in this group [ 249 ].

To note, assigning a warranty period following a negative CTCA should be done with some caution in First Nations peoples due to limited evidence for this population.

Implementation of an Australian telemedicine program supporting remote exercise stress testing with cardiology specialist support has been shown to reduce waiting times. The program enabled a signi ﬁ cant proportion of people to be managed in local health facilities [ 250 ].

2.7. Role of Rapid Access Chest Pain Clinics

Rapid access chest pain clinics can assist with choice of further investigations or management in certain people discharged following an ACS [ 251 ]. Multiple UK studies have found this model to be safe, ef ﬁ cient and cost-effective compared with hospital admission [ 252 ].

Various chest pain clinic models have been trialled throughout Australia. These models seem to deliver similar results to the UK system, regardless of referral patterns or investigations undertaken [ 251 ]. Bene ﬁ ts include more ef ﬁ - cient access to testing and diagnosis, cost savings compared with hospital admission, greater individual satisfaction and, most importantly, equal or improved safety compared with traditional hospital-based care [ 253 – 257 ].

Other bene ﬁ ts demonstrated in Australia include reduced rates of invasive investigations, lower rates of ED representation, and a clear mechanism for timely follow-up of test results.

It is important to prioritise access to these clinics for selected intermediate-risk people with cTn levels ${<\!99^{\mathrm{th}}}$ percentile.

2.8. Re-presentation with Symptoms

People who re-present to ED within 30 days with possible ACS symptoms and who have not already undergone non-invasive testing for CAD and/or coronary ischaemia may warrant further testing. This includes functional or anatomical tests. These people also require a detailed re-appraisal for alternate diagnoses. If re-presentation occurs after prior negative exercise ECG testing, use of investigations with greater sensitivity and speci ﬁ city or an anatomical test should be considered.

2.9. Discharge Planning and Advice

Following comprehensive and structured assessment of people with suspected ACS, people who do not require admission for further assessment and/or management can be discharged. The outcome of ED assessment will determine the guidance given to the person (and their support people) prior to discharge.

Many people will not receive a de ﬁ nitive diagnosis for their symptoms. However, acute, life-threatening diagnoses including AMI and UA will have been deemed to be of very low probability [ 258 ]. Speci ﬁ c discharge advice for non-ACS presentations is not within the scope of this guideline.

2.9.1. Discharge communication for general practitioners To support ongoing management of people after discharge, concise information in the form of a discharge summary must be promptly provided to a person ’ s general practitioner.

2.9.2. Discharge advice for people at low risk for ACS Discharge advice for people identi ﬁ ed as low risk should include the following, both verbally and in written form:

' Evidence-based information on the condition(s) diagnosed and any further investigation/management required. ' Clear communication that the person has been comprehensively assessed to exclude AMI and to determine UA is unlikely. ' A clear statement that CAD has not been excluded, and that follow-up with the person ’ s general practitioner is recommended for assessment and management according to the Australian guideline for assessing and managing cardiovascular disease risk ( cvdcheck.org.au ). ' Information about what steps the person should take if they experience recurrent symptoms. ' Education on cardiovascular health and cardiovascular causes of chest pain and other key symptoms. ' Guidance on where to ﬁ nd reliable sources of online health information and how to contact telephone-based triage services.

The use of a decision support tool may assist in conveying risks of heart disease and of the lack of bene ﬁ t, and possible harm, of further testing in low-risk people (see Supplementary Material B2 ) [ 146 ].

2.9.3. Discharge advice for people at intermediate risk for ACS

Discharge advice for people identi ﬁ ed as intermediate risk should include the following, both verbally and in written form:

' Clear reassurance for the person and their support people that they have been comprehensively assessed as safe to be discharged. ' Clear information on management of existing and/or new symptoms including when to call an ambulance, represent to the ED, or contact their general practitioner. ' Information on referral for outpatient assessment and management. This should include clear guidance on the clinician/clinic referred to, and whether an appointment has already been arranged or whether the person or support people need to do this. If the latter, then a clear timeline and contact details to arrange the appointment should be provided in the written discharge advice. ' Clear guidance on new or continuing medicines, including when and how to take them. ' Education on cardiovascular disease risk and steps that the person can take to reduce their risk. ' Guidance on where to ﬁ nd reliable sources of online health information and how to contact telephone-based triage services.

2.9.4. Discharge advice for people with a prior history of coronary heart disease who have a chronic or stable coronary syndrome

A small number of people presenting to the ED with a prior diagnosis of CAD may be discharged with probable chronic or stable CAD. The advice given needs to balance the following:

1) Reassurance that the person has been comprehensively assessed and is deemed safe for discharge at this time, notwithstanding a probable cardiac cause for their symptoms and presentation. 2) A clear plan for further follow-up for assessment and management. 3) A clear plan for managing existing or new symptoms. 4) Education on their cardiovascular health and reiteration of when to call an ambulance, re-present to ED or contact their general practitioner.

Discharge planning and advice supports reduced ED presentations and better outcomes. Clinicians, including registered nurses and nurse practitioners, should be supported to undertake comprehensive pre-discharge assessment and discharge planning. This is important to help manage a person ’ s anxiety; high levels of anxiety are associated with an increased likelihood of symptom recurrence and re-presentation to hospital [ 259 , 260 ].

Shared decision making is strongly encouraged. More research is needed on how to best implement shared decision making to achieve the goals of people at risk of or living with cardiovascular disease [ 34 , 36 , 261 – 263 ].

2.10. Primary Care and Regional and Remote Presentations

Recommendations

|Recommendation| Strength of recommendation | Certainty of nevidence | |---|---|---| |For people with suspected|Consensus|| |ACS initially evaluated in||| |the primary care setting.||| | prompt transfer to a facility||| |where definitive risk||| |assessment can occur||| |(e.g. ED) is recommended.||| |Metropolitan health services|Strong|LOW| |should establish centralised||| | support systems for regional||| | and remote health services||| |to facilitate:||| | prompt assistance with||| |ECG interpretation and||| |access to troponin results||| |when on-site access is||| | not available||| | provision of clinical advice||| |to healthcare professionals||| |· access to cardiac||| | investigations if required.|||

Evidence supporting the recommendations

All people with suspected ACS should have the opportunity to receive best practice care, regardless of their geographic location in Australia. Coordinated centralised systems of care are needed to achieve this. Telehealth models allow prompt and consistent access to specialist services for health services outside major tertiary centres.

An Australian state-based model has demonstrated that access to early cardiologist support for ECG interpretation, POC troponin results and cardiology-assisted decision-making is associated with reduced mortality [ 264 ]. In addition, an Australian cluster randomised trial of in-hours, routine tertiary level support versus usual care for people in hospitals without emergency physicians showed fewer missed STEMIs [ 71 ].

2.10.1. Considerations for primary care presentation

Initial assessment

As outlined previously, assessment of ACS incorporates the following:

' ECG ﬁ ndings ' clinical ﬁ ndings from history and physical examination ' troponin testing.

The ability of a healthcare professional to reliably diagnose or, just as importantly, exclude ACS is determined by their capacity to perform and interpret these components. If the

clinician suspects ACS, transfer to the nearest medical facility where de ﬁ nitive assessment for ACS can occur is mandatory.

Initial ECG assessment

People presenting with suspected ACS require prompt access to an ECG (within 10 minutes) and interpretation by a suitably trained clinician (section 2.2 Initial ECG Assessment ). However, if ACS is suspected, ECG acquisition should not delay transfer to a facility that can perform serial troponin testing and provide reperfusion therapy, as delays are associated with harm [ 265 – 270 ].

If an ECG cannot be performed within 10 minutes, prompt transfer via ambulance to a location where an ECG can be performed is required. This may mean the ﬁ rst ECG is evaluated by trained paramedics.

If an ECG is non-ischaemic and the clinical presentation does not align with ACS as the likely diagnosis, it is reasonable to continue assessment in the primary care setting.

Troponin testing

If ACS remains a possible diagnosis after initial history, examination and ECG assessment, and cTn testing is required, the person should be transferred to the nearest facility (usually an ED) for de ﬁ nitive risk assessment [ 16 , 38 , 271 ].

In Australia, there are no single test strategies using POC contemporary troponin assays to exclude AMI [ 122 ]. Hence, serial testing is required, which is often not feasible in the primary care setting (section 2.3 Biomarkers and 2.4 Risk Assessment and Clinical Decision Pathways for Suspected ACS ). Hs-cTn POC assays are available, but not widely distributed. Currently, there is limited evidence for single test strategies to exclude MI in primary care settings [ 111 ].

Risk assessment and clinical decision pathways

In a systematic review of older risk assessment rules for use in the primary care setting without cTn results, no difference was seen between use of a risk score or a general practitioner ’ s clinical judgement in the ability to rule out ACS [ 272 ]. As such, risk scores such as the Marburg Heart Score, Grijseels and Bruins Slot rules are not recommended for exclusion of ACS in a primary care setting [ 273 ].

2.10.2. Considerations for regional and remote presentations

Presentations to regional and remote settings impose challenges, including limited human and technical resources and potentially prolonged transfer times [ 274 ]. Roughly one quarter of people presenting with chest pain require transfer to at least one other hospital. As a result, median times to angiography and overall length of stay are prolonged [ 275 ].

Geographic location also affects clinical outcomes. Greater mortality is observed at 18 months post-event amongst people presenting with ACS to non-PCI capable centres, most of which are in regional or remote locations [ 276 , 277 ].

While the initial assessment remains unchanged, key factors in ﬂ uencing the decision to transfer people with suspected ACS include:

' local service capabilities and support available in regional and remote settings

' availability of relevant investigations including chest Xrays, cTn testing and/or other cardiac tests (e.g. CTCA, exercise stress testing, echocardiography) ' the healthcare professional ’ s clinical judgement.

Initial ECG assessment

If the ECG can be performed but not interpreted, it is reasonable to seek urgent remote evaluation (e.g. via telehealth) [ 71 ].

When the clinical and ECG assessment supports a diagnosis of ACOMI, consideration of urgent reperfusion therapy is required. Urgent transfer of the person to the nearest facility for ﬁ brinolysis or primary PCI is needed (section 3 Hospital Care and Reperfusion ).

Troponin testing

Many regional and remote settings are reliant on contemporary cTn assays, including POC platforms [ 137 ]. Clinicians must be aware of the type of troponin assay in use locally and ensure results are used in an evidence-based CDP (section 2.3 Biomarkers and 2.4 Risk Assessment and Clinical Decision Pathways for Suspected ACS ).

Where contemporary cTn assays are in use, UA should be considered in the presence of normal cTn results if clinical suspicion for ACS is high based on ECG interpretation and/ or clinical history. Further serial cTn testing over 6 – 8 hours should occur [ 38 ]. Management may include initial treatment for presumed ACS, a period of continuous cardiac monitoring and/or transfer to a PCI-capable centre.

Risk assessment and clinical decision pathways

Evidence supporting the use of clinical risk scores without incorporating troponin values is limited. In the absence of hs-cTn assays, incorporation of contemporary cTn results with clinical risk scores within a validated CDP is crucial (section 2.4.1.2 Clinical score-based clinical decision pathways and Supplementary Material B2 ). In a rural New Zealand setting, use of the EDACS accelerated diagnostic pathway with serial POC contemporary cTn measurements safely strati ﬁ ed risk in people with suspected ACS (see Supplementary Material B2 ) [ 278 ].

Further diagnostic testing

If a particular diagnostic test is required (section 2.6 Further Diagnostic Testing for People with Suspected ACS ) but unavailable regionally, transfer to another facility should be considered.

Tertiary centres have an obligation to support appropriate testing in people from regional and remote areas. Decisions on further diagnostic testing can be informed by consultation with metropolitancardiacteamsor,whenavailable,rapidaccesschest pain clinics. Remote access to such clinics may help improve diagnostic pathways for people in regional and remote settings.

Shared decision making

Shared decision making is particularly vital for people with suspected ACS living regionally or remotely, when considering investigation and management options (section 2.9 Discharge Planning and Advice ). Decisions should consider the person ’ s preferences for ongoing management, which may include remaining in a resource-poor setting or being transferred away from community.

3. Hospital Care and Reperfusion

3.1. Acute Management of STEMI – Reperfusion for STEMI

3.1.1. Eligibility for reperfusion Recommendations

|Recommendation| Strength of recommendation | Certainty of evidence | |---|---|---| ||Strong|Moderate| | In people with STEMI within 12 hours of ||Moderate| |symptom onset, perform||| |emergency reperfusion||| |with either primary PCI||| | or fibrinolytic therapy.||| | In people with STEMI,|Strong|Moderate| | symptom onset over||Moderate| |12 hours before||Moderate| | presentation and||Moderate| |evidence of continuing||| |myocardial ischaemia||| |(persistent ischaemic||| |symptoms,||| |haemodynamic||| |compromise, and/or||| |life-threatening||| |arrhythmias),||| | perform emergency||| | reperfusion with||| | primary PCI.|||

Evidence supporting the recommendations

Timely reperfusion limits the extent of MI and reduces mortality by minimising total ischaemic time [ 279 – 282 ]. The impact on mortality is greatest in the ﬁ rst hour after symptom onset and diminishes with time, virtually dissipating by 12 hours [ 283 ].

Routine emergency reperfusion in people who present more than 12 hours after symptom onset is not recommended. However, a primary PCI strategy may be considered in the presence of ongoing ischaemia, as observational studies support a survival bene ﬁ t. In addition, two small, randomised trials have reported reductions in infarct size and four-year mortality [ 284 – 287 ].

For people with STE and multivessel disease (MVD), complete revascularisation should be the goal (section 3.7 Treatment for ACS with Multivessel Disease without Cardiogenic Shock ).

Practice points

' When deciding on eligibility for reperfusion, consider cognitive function, comorbidities, and frailty which

in ﬂ uence a person ’ s overall survival. The superiority of PCI over ﬁ brinolysis appears to extend to older people. However, trials have been small, with few very elderly people $(>\!90$ years), and have not included evaluation of frailty or comorbidity.

3.1.2. Choice of reperfusion strategy Recommendations

|Recommendation| Strength of recommendation || |---|---|---| ||| Certainty of evidence | | In people with STEMI|Strong|High| |within 12 hours of||| |symptom onset, primary||| |PCI is the preferred||| |reperfusion strategy||| |over fibrinolysis, if it||| |can be performed within||| |120 minutes of first||| |medical contact.||| |||| | In people with STEMI| Strong|Moderate| |within 12 hours of||| |symptom onset, perform||| |fibrinolysis if primary||| |PCI cannot be delivered||| |within 120 minutes of||| |first medical contact.|||

Evidence supporting the recommendations

Currently, the options for reperfusion for STEMI are primary PCI or ﬁ brinolytic therapy, with the choice dependent on several factors ( Figure 12 ). If primary PCI is the chosen reperfusion strategy, adopt quality assurance targets to reduce delay to wire crossing.

For people presenting to primary PCI-capable centres, ﬁ rst medical contact to wire crossing time should not exceed 60 minutes [ 288 ]. For people presenting to non-PCI-capable centres, ﬁ rst medical contact to wire crossing time should not exceed 90 minutes [ 288 ]. However, in keeping with the evidence, primary PCI is still the preferred strategy if it can be performed within 120 minutes.

Fibrinolytic therapy, compared with control, reduced overall mortality at 35 days with a relative risk of 0.82 $(95\%$ con ﬁ dence interval (CI) 0.77 – 0.87) based on data from nine trials conducted during the 1980s and 1990s involving 58,600 people [ 289 ].

A meta-analysis of 23 trials including 7,739 people with STEMI compared primary PCI to ﬁ brinolytic therapy. Primary PCI was found to be better at reducing the combined end-point of short-term death, non-fatal reinfarction and stroke $8\%$ vs $14\%$ , $\mathtt{p}{<}0.0001$ ), bene ﬁ ts that persisted in the longer term [ 280 ].

An observational analysis from the National Registry of Myocardial Infarction in the United States demonstrated that

![Symptom FMCSTEMI onset diagnosis AimFMC-to-wire PCl centre Primary PCI crossingtime<60mins OR Immediate AimFMC-to-wire YES transferto Primary PCI crossing<90mins Pathways and PClcentre decisions in CanPCIbe reperfusion Ems or performed Early transfer non-PCI within for coronary centre YES 120mins? angiography between Immediate Fibrinolysis 2O 2-24 hours fibrinolysis successful? Immediate AimFMC-to-needle transferfor time≤30mins rescuePCI Ifcardiogenicshock,immediatetransfertoPClcentrewherepossible Tine delays in Patient reperfusion delay Systemdelay Total ischaemic time ](https://venus-trag-1258344701.cos-internal.ap-guangzhou.tencentcos.cn/userUpload/is-62e36cd9/2025-04-10/9425acd5-3982-494a-8913-f70e1755ef79/9425acd5-3982-494a-8913-f70e1755ef79.jpg?q-sign-algorithm=sha1&q-ak=AKID61g5D5fy1TjiRv84nEOHtFJ8gyzjCPL0&q-sign-time=1744240805%3B1744244405&q-key-time=1744240805%3B1744244405&q-header-list=host&q-url-param-list=&q-signature=4d39f2b34bf53bb324b1de0dc2685b219ade6a4f) Figure 12 Decision making and organisation of reperfusion strategies within ﬁ rst 12 hours of medical contact. Adapted from Chew et al. [ 38 ]. Abbreviations: EMS, emergency medical service; FMC, ﬁ rst medical contact; PCI, percutaneous coronary intervention; STEMI, ST-segment elevation myocardial infarction.

the relative bene ﬁ t of primary PCI over ﬁ brinolysis was lost after a delay to PCI of 121 minutes [ 290 ].

Importantly, the trials comparing primary PCI and ﬁ brinolysis did not include routine early angiography in the ﬁ brinolytic arms. There is evidence that an early ﬁ brinolysis strategy followed by routine early angiography may be noninferior to PCI (section 3.2 Ongoing Management of Fibrinolytic-Treated People ). Also, very early administration of ﬁ brinolysis in the pre-hospital setting may confer superior outcomes to PCI, especially among people presenting within two hours of symptom onset [ 291 ].

Ef ﬁ cacy of ﬁ brinolysis has not been shown in people presenting 12 or more hours after onset of symptoms. Given the lower ef ﬁ cacy and persistent bleeding risks associated with ﬁ brinolysis in such people, reperfusion with PCI is preferred in people with continued myocardial ischaemia (section 3.1.1 Eligibility for reperfusion ) [ 286 , 287 , 292 – 295 ].

Practice points

' Establish effective care pathways tailored to the speci ﬁ c healthcare services available in the region. These pathways should include ambulance, primary health, emergency, cardiology and regional or remote healthcare services to optimise reperfusion times. ' Implement speci ﬁ c measures to reduce time to reperfusion [ 17 ], such as: B pre-hospital ECG and single-call catheter laboratory activation (i.e. streamlined communication between emergency services and the receiving hospital to bypass the ED and reduce reperfusion delay) B pre-hospital ﬁ brinolysis by suitably trained clinicians (e.g. paramedics, nurses, First Nations health practitioners) B direct transfer to PCI-capable hospitals and direct transfer to the catheterisation laboratory on hospital arrival.

3.1.3. Administration of ﬁ brinolytic therapy Recommendations

|Recommendation|Strength of|| |---|---|---| || recommendation | Certainty of evidence | | In people with STEMI| Strong|Moderate| |for whom fibrinolysis||| |is the preferred||| |reperfusion strategy,||| |it should be delivered||| |within 30 minutes of||| |first medical contact.||| |Consider pre-hospital||| |administration.||| |||| | In people aged|Strong| Moderate| |>70 years, half the||| |standard dose of||| |tenecteplase is||| |recommended as part||| | of a pharmaco-invasive||| |strategy.|||

Evidence supporting the recommendations

Timing of ﬁ brinolytic therapy

Fibrinolysis should be considered when the anticipated delay to primary PCI is ${>}120$ minutes and there are no absolute contraindications. Fibrinolysis should be delivered as soon as possible after the diagnosis is established, ideally within 30 minutes of ﬁ rst medical contact and, if possible, prior to hospital arrival [ 17 , 288 , 296 , 297 ].

People with an absolute contraindication should be transferred for PCI ( Table 9 ). People with a relative contraindication need to have the risks and bene ﬁ ts of treatment considered.

The STREAM study (n=1,892) compared a pharmacoinvasive approach consisting of pre-hospital ﬁ brinolytic therapy and routine angiography 6 – 24 hours later against primary PCI in people unable to receive the latter within 60 minutes. There was no signi ﬁ cant difference in the primary composite endpoint (death, cardiogenic shock, heart failure and recurrent MI) between the groups. Among people aged 75 years and over receiving full dose tenecteplase, higher rates of intracranial haemorrhage were seen, an effect reduced by halving the tenecteplase dose with no change in ef ﬁ cacy [ 298 ].

The subsequent STREAM-2 study $(\mathsf{n}\!\!=\!\!602]$ ) restricted enrolment to older people ( ${\scriptstyle\left\langle{>60}\right\rangle}$ years, mean age 70 years) and compared half dose tenecteplase and routine angiography 6 – 24 hours later against primary PCI [ 299 ].

Table 9 Contraindications for ﬁ brinolysis. Adapted with permission from O ’ Gara et al. [ 270 ].

Absolute contraindications

' Any prior intracerebral haemorrhage ' Known structural cerebral vascular lesion (e.g. arteriovenous malformation) ' Known malignant intracranial neoplasm (primary or metastatic) ' Ischaemic stroke within 3 months B EXCEPT acute ischaemic stroke within 4.5 hours ' Suspected aortic dissection ' Active bleeding or bleeding diathesis (excluding menses) ' Signi ﬁ cant closed-head or facial trauma within 3 months ' Intracranial or intraspinal surgery within 2 months

Relative contraindications

' History of chronic, severe, poorly-controlled hypertension ' Signi ﬁ cant hypertension on presentation (SBP ${>}180~\mathrm{mmHg}$ or DBP . 110 mmHg) ' History of prior ischaemic stroke ${>}3$ months ' Known intracranial pathology not covered in absolute contraindications ' Dementia ' Traumatic or prolonged ( ${\wp}10\ \mathrm{min}$ ) CPR ' Major surgery ( $^{'<3}$ weeks) ' Recent internal bleeding (within 2 to 4 weeks) ' Non-compressible vascular punctures ' Pregnancy ' Active peptic ulcer ' Oral anticoagulant therapy

Abbreviations: CPR, cardiopulmonary resuscitation; DBP, diastolic blood pressure; SBP, systolic blood pressure.

There was no difference between groups in the primary ef ﬁ cacy endpoint. The rate of intracranial haemorrhage in the pharmaco-intensive treatment arm was $1.5\%$ compared with $0\%$ in the PCI arm. To note, half of these events were associated with dosing protocol deviations.

Practice points

' An easily administrable ﬁ brinolytic agent that can be given as a bolus dose, such as tenecteplase, is advisable especially in the pre-hospital setting. ' Currently available ﬁ brinolytics include: B tenecteplase (weight-adjusted [30 – 50 mg] IV bolus and age-adjusted [half-dose] IV bolus) B reteplase (10 units IV followed by 10 units IV, 30 minutes later) B alteplase (weight adjusted accelerated bolus and infusion regimen).

3.1.4. Procedural recommendations in primary percutaneous coronary intervention Recommendations

| Recommendation | Strength of recommendation | Certainty of evidence | |---|---|---| | For people with STEMI|Consensus|| |at a PCI-capable centre,||| |deliver primary PCI||| |within 60 minutes of||| |arrival. For people with||| |STEMI transferred||| |from a non-PCI centre,||| |deliver primary PCI||| |within 90 minutes of||| |first medical contact.||| |Use radial access over|Strong|High| |femoral access when||| |performing primary||| |PCI, unless||| | contraindicated.||| | In people undergoing|Strong|| |||Moderate| |primary PCI, do not||| | perform routine thrombus aspiration ||| |of the infarct-related||| |artery (IRA).||| |||| ||Strong|| |asymptomatic and||| | stable for more than 48 hours following ||| |occlusion of an IRA,||| |do not perform routine||| |PCI to this artery.|||

Evidence supporting the recommendations Time targets for primary PCI

For people with a diagnosis of STEMI, it is important to limit system delay (time from ﬁ rst medical contact or arrival at a healthcare system to reperfusion), as this is a predictor of mortality [ 300 ]. Targets for delivery of primary PCI include within 60 minutes from ﬁ rst medical contact of a person arriving at a PCI-capable centre, or within 90 minutes from ﬁ rst medical contact if transferred from a non-PCI capable centre [ 288 ]. Pre-activation of the catheterisation laboratory when the diagnosis is made in the pre-hospital setting (and bypassing the ED on arrival) reduces treatment delays [ 301 , 302 ].

Radial versus femoral access

Multiple RCTs and an individual person-level data metaanalysis $\mathbf{(n{=}21,}600)$ ) have shown a bene ﬁ t of radial over femoral access in people with STEMI with a reduction in total mortality ( $1.6\%$ vs $2.1\%$ , hazard ratio [HR] 0.77, $95\%$ CI 0.63 – 0.95) and major bleeding ( $1.5\%$ vs $2.7\%$ , OR 0.55, $95\%$ CI

0.45 – 0.67) [ 303 – 307 ]. A radial- ﬁ rst approach is therefore recommended for primary PCI, unless precluded by contraindications [ 142 , 296 , 303 , 308 ].

Treatment of the infarct-related artery

Routine thrombus aspiration of the IRA has been associated with a small but signi ﬁ cantly increased risk of stroke without a survival bene ﬁ t, compared with routine stenting [ 309 – 311 ]. Thrombus aspiration may be considered in people with high thrombus burden with careful attention to technical strategies to avoid embolisation.

When stenting is required, meta-analyses have shown that currently available drug eluting stents have better ef ﬁ cacy and safety than bare metal stents, with lower restenosis and stent thrombosis [ 288 , 312 – 317 ]. This includes people at high bleeding risk (HBR), people who require triple antithrombotic therapy or short duration dual antiplatelet therapy (DAPT).

Routine deferred stenting of the IRA is not recommended due to an increased risk of unplanned target vessel revascularisation without a survival bene ﬁ t [ 318 , 319 ]. Deferred stenting can be considered in select people, for example, those with residual large thrombus burden where immediate PCI is unlikely to be successful [ 320 , 321 ].

Routine PCI of a completely occluded IRA in asymptomatic stable people who are ${>}48$ hours from symptom onset has been associated with an increased risk of recurrent MI, with no survival or major cardiovascular outcome bene ﬁ t, compared with medical therapy [ 293 , 322 ].

Practice points

' Where stenting is required, drug eluting stents are preferred over bare metal stents. ' Routine deferred stenting of the IRA is not recommended. In people with STEMI and risk factors for slow or no re ﬂ ow, such as high thrombus burden, consider deferred stent implantation. ' In people with STEMI where primary PCI of the IRA is not feasible (e.g. severe left main artery disease or an uncrossable coronary lesion), CABG may be an appropriate primary reperfusion strategy. CABG may be particularly appropriate if there is a large area of myocardium at risk and surgery is available in a timely manner (section 3.8 Coronary Artery Bypass Graft Surgery in ACS ) [ 323 , 324 ].

Women

' Understand that women with STEMI have documented delays to reperfusion, lower rates of invasive angiography and radial access and poorer outcomes compared with men [ 10 – 12 , 325 ]. ' Improve clinician awareness of sex-speci ﬁ c differences in: B presenting symptoms B ECG diagnostic criteria B underlying MI aetiologies, such as an increased proportion of SCAD and MINOCA, as this may improve outcomes. ' Perform primary PCI as the preferred revascularisation strategy in pregnant women with STEMI, except when

caused by SCAD. Use appropriate shielding to minimise radiation exposure to the foetus [ 308 ].

3.2. Ongoing Management of Fibrinolytic-Treated People

Recommendations

|Recommendation|Strength of| Certainty of evidence | |---|---|---| || recommendation || |People successfully|Strong| Moderate| |treated with fibrinolytic||| |therapy should be||| |transferred to a PCI-||| |capable centre as soon||| | as possible. Angiography||| |should be performed||| |within 2-24 hours of||| |arrival.||| |||| | Consider transferring|Weak|Moderate| |people as soon as||| |possible to a PCI-capable||| |centre if fibrinolytic||| |therapy is unsuccessful.||| |If appropriate, consider||| |subsequent PCI at||| |the centre.|||

Evidence supporting the recommendations

A network meta-analysis of 31 RCTs compared outcomes of people randomised to ﬁ brinolytic therapy $\scriptstyle(\mathbf{n}=4,212)$ , primary PCI (n=6,139), or ﬁ brinolysis followed by routine early PCI $\scriptstyle(\mathtt{n}=5,006)$ . The latter was categorised as facilitated PCI when the median time interval between ﬁ brinolysis to PCI was ${<}2$ hours $\mathbf{(n{=}2,}259)$ ) and as a pharmaco-invasive approach when this interval was ${\geq}2$ hours $\mathsf{(n{=}2,747)}$ ) [ 326 ]. Primary PCI was associated with the lowest risk of mortality (odds ratio (OR) 0.73, $95\%$ CI 0.61 – 0.89) when compared with ﬁ brinolysis alone. However, among strategies in people receiving initial ﬁ brinolysis, the pharmaco-invasive approach was associated with a trend towards lower mortality (OR 0.79, $95\%$ CI 0.59 – 1.08) and showed signi ﬁ cantly less reinfarction (OR 0.53, $95\%$ CI 0.37 – 0.75) in comparison to ﬁ brinolysis alone. Furthermore, in comparison to a facilitated approach, a Bayesian analysis showed the probability of adverse outcomes was lower with a pharmaco-invasive approach [ 326 ].

Another meta-analysis of seven studies comparing only early routine PCI after ﬁ brinolysis versus standard therapy (i.e. ﬁ brinolysis alone or rescue PCI where indicated) found no signi ﬁ cant difference in 30-day mortality (OR 0.87, $95\%$ CI

0.59 – 1.30, $\mathtt{p}{=}0.51$ ). However, the study did ﬁ nd a signi ﬁ cant reduction in reinfarction (OR 0.55, $95\%$ CI 0.36 – 0.82, $\mathtt{p}{=}0.003\$ ) and the composite of death and reinfarction (OR 0.65, $95\%$ CI 0.49 – 0.88, $\mathsf{p{=}0.004})$ at 30 days, without a signi ﬁ cant increase in major bleeding (OR 0.93, $95\%$ CI 0.67 – 1.34). These bene ﬁ ts were sustained to 12 months [ 327 ].

Once a pharmaco-invasive approach is chosen, post-hoc analyses suggest the bene ﬁ t is greatest the sooner PCI is achieved from symptom onset or administration of ﬁ brinolysis (without transitioning to a facilitated approach). A meta-analysis of six randomised trials $\scriptstyle(\mathfrak{n}=1,238)$ ), demonstrated reduced 30-day recurrent ischaemia where angiography was achieved within 2 or 4 hours in comparison to beyond 4 hours ( $(3.7\%$ vs $3.7\%$ vs $7.9\%$ , $\mathtt{p}{=}0.02)$ , but no reduction in 30-day mortality or reinfarction [ 328 ].

In a meta-analysis of eight RCTs (n=1,177), rescue PCI for failed ﬁ brinolysis compared with conservative treatment was associated with a signi ﬁ cant reduction in reinfarction (risk ratio [RR] 0.58, $95\%$ CI 0.35 – 0.97), but no reduction in mortality [ 329 ]. In people being treated with ﬁ brinolytics who are not in a PCI-capable hospital, care pathways should be developed to enable, when appropriate, immediate or early transfer for angiography ( Figure 12 ) [ 330 ].

Practice points

' Perform regular ECG monitoring following ﬁ brinolytic therapy according to local protocols, continuing until the person is pain free and for at least 60 – 90 minutes postﬁ brinolysis. ' Recognise failed reperfusion in people treated by ﬁ brinolytic therapy if they exhibit any of the following: B ongoing ischaemic chest pain B ${\leq}50\%$ ST recovery on an ECG performed 60 – 90 minutes after ﬁ brinolysis B or ongoing haemodynamic instability.

First Nations peoples

' Ensure that education about ongoing management is culturally appropriate and includes the importance of transferring to a PCI-capable centre when necessary. ' Provide cultural and language support before, during and after transfer, ensuring family and cultural considerations are addressed by appropriately trained staff.

People living in regional and remote areas

' Establish formal care pathways to facilitate timely and ef ﬁ cient transfer between non-PCI capable centres and PCI-capable centres, often located in metropolitan areas. These pathways should address logistical challenges and ensure seamless continuity of care. ' Consider an additional half-dose of ﬁ brinolytics with caution if ﬁ brinolysis fails and timely transfer for rescue PCI is not feasible. However, this practice point is based on limited evidence from a single prospective trial with limited applicability to contemporary remote Australian settings [ 331 ].

3.3. Acute Management of NSTEACS

3.3.1. Risk strati ﬁ cation for people with con ﬁ rmed NSTEACS Recommendations

|Recommendation|Strength of| Certainty of evidence High | |---|---|---| ||recommendation| Certainty of evidence High | | In people with NSTEACS,|Weak| Certainty of evidence High | | consider using the GRACE|| Certainty of evidence High | |risk score to determine|| Certainty of evidence High | |short- and long-term|| Certainty of evidence High | | cardiovascular prognosis.||| |||| | In people with ACS|| Moderate| |undergoing coronary||| |angiography, consider||| |using bleeding risk||| |scores to determine||| |short-term bleeding risk.|||

Evidence supporting the recommendations

Assessment of the short- and longer-term risk of death and recurrent ischaemic and bleeding events in people admitted with ACS can guide the need for, and timing of, invasive management. Risk assessment can also guide selection and duration of antithrombotic therapy. Clinical assessment and objective tools may both contribute to risk strati ﬁ cation in people with con ﬁ rmed NSTEACS.

Clinical risk assessment

A subset of people presents with factors that are associated with a high risk of short-term mortality. These include people with haemodynamic instability/cardiogenic shock, lifethreatening arrhythmias, mechanical complications of MI, acute heart failure clearly related to NSTEACS, and/or ongoing symptoms in the presence of high-risk ECG criteria such as ST-segment depression ${>}1$ mm in ${>}6$ leads additional to STE in aVR and/or V1, Wellens criteria on ECG or recurrent intermittent STE (section 2.2 Initial ECG Assessment ). An early invasive management strategy is recommended for these people (section 3.3.3 Timing of invasive management for NSTEACS ).

In the absence of these very high-risk criteria, clinical risk assessment performs poorly compared with objective risk tools in determining prognosis.

Objective risk prediction for ischaemic outcomes In people admitted with NSTEACS, prognosis is well predicted by Global Registry of Acute Coronary Events (GRACE) risk score which performs better than Thrombolysis in myocardial infarction (TIMI) risk and subjective clinical assessment [ 275 , 332 – 334 ]. Observational analyses have

shown guideline-directed care is associated with greater survival gains in higher risk people. However, the intensity of care is often inversely proportionate to the level of objectively determined individual risk [ 335 – 337 ].

While it is intuitive that objective risk scores may help identify people with ACS who would bene ﬁ t from riskconcordant delivery of care, two prospective cluster randomised trials have failed to demonstrate an effect of routine GRACE risk score implementation on guideline-indicated treatments and clinical outcomes in people hospitalised with ACS [ 338 , 339 ]. Baseline levels of hs-cTn have been shown to be strongly associated with death or MI at 30 days [ 340 ].

Risk prediction for bleeding outcomes

Major bleeding in hospital is associated with increased mortality and a range of scores have been developed to predict this outcome among people presenting with ACS ( Table 10 ).

A comparison of scoring systems reported that Acute coronary treatment and intervention outcomes network (ACTION) had the highest discrimination [C statistic 0.767 (0.737 – 0.797), three studies], followed by Can rapid risk strati ﬁ cation of unstable angina patients suppress adverse outcomes with early implementation of the ACC/AHA guidelines (CRUSADE) [C statistic 0.714 (0.659 – 0.779), 12 studies] and Acute catheterization and urgent intervention triage strategy (ACUITY) [C statistic 0.711 (0.626 – 0.797), seven studies] [ 341 ]. The Academic Research Consortium high bleeding risk (ARC-HBR) score is an alternative pragmatic approach recommended by European guidelines [ 342 ].

These scores have been developed in populations with a high prevalence of coronary angiography and receipt of DAPT. While they may be considered when choosing procedural and antiplatelet strategies, their impact on outcomes has not been evaluated.

Practice points

' Recognise that GRACE risk scores were developed before the introduction of hs-cTn assays. However, most people identi ﬁ ed as high risk by the GRACE score are similarly identi ﬁ ed using hs-cTn testing alone. ' Prioritise bleeding risk over ischaemic risk when making decisions about the duration of DAPT in people at risk of both bleeding and ischaemic events, as suggested by observational data (section 3.4 Antiplatelet Therapy in the Acute Phase and 3.5 Anticoagulant Therapy in the Acute Phase ) [ 343 ].

Women

' Use the GRACE 3.0 score for risk assessment in women with NSTEACS, as it provides a more accurate estimation of mortality risk than the GRACE 2.0 score (which

Table 10

Parameters of bleeding risk scores. Adapted with permission from Wang et al. [ 341 ].

Parameter CRUSADE ACUITY ACTION GRACE HAS-BLED Sex x x x Renal function x x x x x Haematocrit/Anaemia x x Heart rate x x x Blood pressure x x x Congestive heart failure x Vascular disease x Diabetes x x Age x x x x Antithrombotic medicines x x x Presentation x White blood cell count x Weight x Cardiac arrest x ECG ST changes x Abnormal biomarkers x Killip class x Stroke x Hypertension x Liver disease x Bleeding history x Labile INR x Alcohol use x

Abbreviations: ACTION, Acute coronary treatment and intervention outcomes network; ACUITY, Acute catheterization and urgent intervention triage strategy; CRUSADE, Can rapid risk strati ﬁ cation of unstable angina patients suppress adverse outcomes with early implementation of the ACC/AHA guidelines; ECG, electrocardiogram; GRACE, Global Registry of Acute Coronary Events; HAS-BLED, Hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile INR, elderly, drugs/alcohol concomitantly; INR, international normalised ratio.

underestimates mortality) and helps address sex inequalities in risk strati ﬁ cation [ 344 ].

Older adults

' Consider that the GRACE risk score heavily weights age and does not account for characteristics common in older adults such as frailty, multimorbidity, polypharmacy and cognitive dysfunction, which can contribute to higher risk scores [ 345 ].

' Assess frailty in older adults, as it is independently associated with adverse outcomes and increased bleeding risk [ 346 ]. Use validated frailty assessment tools to guide management decisions [ 347 – 350 ]. ' Consider a conservative management approach in older adults, even if they are deemed high risk for ischaemic events based on objective scoring, particularly when frailty and bleeding risk are signi ﬁ cant concerns.

3.3.2. Routine versus selective invasive management for NSTEACS Recommendations

| Recommendation | Strength of recommendation | Certainty of evidence | |---|---|---| | In people with|Strong|High| |NSTEACS at high or||| |very high risk of||| |adverse cardiovascular||| |events, perform routine||| |invasive coronary||| | angiography, with||| |coronary||| |revascularisation (PCI||| |or CABG) where||| | appropriate.||| |||| | In people with|Weak|Moderate| | NSTEACS not at high||| |or very high risk of||| | adverse cardiovascular events, testing for ||| |inducible ischaemia||| |||| | (e.g. stress testing) may guide the need for ||| |||| | invasive coronary angiography. |||

Evidence supporting the recommendations

People with con ﬁ rmed NSTEACS at high risk of adverse cardiovascular events or death include those with:

' con ﬁ rmed diagnosis of NSTEMI according to the Fourth UDMI ' high risk according to hs-cTn algorithms (section 2.4.1.1 High-sensitivity troponin-based clinical decision pathways ) ' dynamic ST-segment or T wave changes ' transient STE ' GRACE risk score ${>}140$ .

People with con ﬁ rmed NSTEACS at very high risk of adverse cardiovascular events or death include those with:

' haemodynamic instability or cardiogenic shock ' life-threatening arrhythmias ' mechanical complications of MI ' ongoing symptoms in the presence of ECG criteria such as ST-segment depression . 1 mm in ${>}6$ leads additional to STE in aVR and/or V1, or Wellens criteria on ECG (section 2.2 Initial ECG Assessment )

' recurrent intermittent STE.

A routine invasive approach (coronary angiography) with subsequent revascularisation (PCI or CABG as indicated) in peoplewith NSTEACS hasbeen studied in systematic reviews, meta-analyses and RCTs, in the context of evolving adjunctive

pharmacotherapies and interventional practices [ 351 – 353 ]. Overall, a routine invasive approach in people with NSTEACS has net bene ﬁ ts in reducing the composite endpoints of death, recurrent MI and rehospitalisation for ischaemia. However, most of this bene ﬁ t is in non-fatal events and only seen in people at high and very high risk [ 354 , 355 ].

A 2016 meta-analysis of 12 RCTs $(\tt n{=}9,650)$ ) of people with NSTEACS found that routine invasive angiography reduced the composite endpoint of MI and death (OR 0.86, $95\%$ CI 0.77 – 0.96) at mean 39-month follow-up, compared with a selective invasive approach [ 355 ]. Consistent with past meta-analyses, this reduction was driven by lower risk of recurrent MIs (OR 0.78, $95\% $ CI 0.68 – 0.88) with non-signi ﬁ cant reduction in risk of mortality (OR 0.88, $95\%$ CI 0.77 – 1.01) [ 356 ].

The bene ﬁ t of a routine invasive approach is greater in people with high-risk features with absolute risk reductions in MI and cardiovascular death of $2\%$ , $4\%$ and $11\%$ in people at low, intermediate and high risk respectively, as determined by GRACE risk score [ 353 ]. In addition, RCTs investigating routine versus invasive strategies pre-dated the use of hs-cTn.

In admitted non-high-risk people with NSTEACS, invasive management may be guided by non-invasive anatomic or functional testing. This can reduce the need for invasive angiography and is predictive of excellent short- and midterm prognosis (section 2.6 Further Diagnostic Testing for People with Suspected ACS ) [ 357 – 360 ].

Practice points

' Consider the goals of therapy, individual preferences and impact of other major comorbidities when deciding on the appropriateness of a routine invasive approach for people with NSTEACS. ' Use anatomical imaging with CTCA instead of functional testing to exclude or de ﬁ ne CAD in people with NSTEACS who: B are at high or very high risk of adverse cardiovascular events B do not have known CAD B present with an unclear NSTEACS diagnosis (section 2.6 Further Diagnostic Testing for People with Suspected ACS ) [ 361 , 362 ].

3.3.3. Timing of invasive management for NSTEACS Recommendations

|Recommendation|Strength of|Certainty of| |---|---|---| |Recommendation|recommendation|evidence| | In people with|Consensus|| |||| | NSTEACS with very||| |high-risk criteria, an||| |immediate invasive||| |strategy within 2||| |hours of diagnosis is||| | recommended. |||

|(continued).||| |---|---|---| |Recommendation| Strength of recommendation | Certainty of evidence High | ||| Certainty of evidence High | | In people with|Weak|| |NSTEACS with||| |high-risk criteria,||| | consider an early||| | within 24 hours of diagnosis. ||| | within 24 hours of diagnosis. ||| | within 24 hours of diagnosis. |||

Evidence supporting the recommendations

Multiple RCTs (the largest being TIMACS and VERDICT) and meta-analyses have investigated the timing of invasive coronary angiography in people with NSTEACS [ 363 , 364 ]. An early invasive strategy was usually de ﬁ ned as within 24 hours (e.g. median of 14 hours after randomisation in TIMACS), while a delayed invasive strategy was usually de ﬁ ned as within 2 – 3 days (median 50 hours and 62 hours in the TIMACS and VERDICT trials, respectively). Overall, these studies found that an early invasive strategy did not confer a bene ﬁ t in mortality, MI and stroke, compared with a delayed invasive strategy, when performed in all people with NSTEACS without consideration of individual risk [ 365 ]. Therefore, the timing for

invasive management of NSTEACS must take a person ’ s risk into account.

Unstable or very high-risk people with NSTEACS have largely been excluded from RCTs investigating an early versus delayed invasive approach. In these people, an immediate (i.e. within two hours of hospital admission) invasive strategy is recommended due to their presumed poor prognosis in the absence of invasive management. This is based on expert opinion, rather than strong randomised data ( Figure 13 ).

In high-risk people with NSTEACS, the TIMACS trial found a reduction in death, MI and stroke at six months associated with early versus delayed (median time 50 hours) intervention ( $14\%$ vs $21\%,$ , $\mathtt{p}{=}0.005,$ in the subgroup of people with a GRACE risk score ${>}140$ , with no increase in major bleeding [ 363 ]. A meta-analysis (eight RCTs, $\scriptstyle{\mathfrak{n}}=5,324$ people) investigating timing of invasive strategy based on individual participant data or standardised tabulated data found lower mortality with an early invasive strategy in people with elevated cardiac biomarkers at baseline (HR 0.76, $95\%$ CI 0.581 – 0.996), diabetes (HR 0.67, $95\%$ CI 0.45 – 0.99), a GRACE risk score ${>}140$ (HR 0.70, $95\%$ CI 0.52 – 0.95), and aged 75 years and older (HR 0.65, $95\%$ CI 0.46 – 0.93) although tests for risk-treatment interactions were inconclusive [ 366 ]. However, the GRACE scores calculated in these trials used CK-MB and earlier troponin assays, with no data to guide early angiography in people with elevated GRACE scores based on hs-cTn assays.

![NSTEACS Very high risk based on haemodynamic High risk on hs-cTn algorithms instability/shock: Dynamic ST segment or Life-threatening arrhythmias Non-high riskpeoplein T wave changes Mechanical complicationsofMI whominvasivestrategyischosen Transient ST elevation Ongoing symptoms with ECG changes GRACEscore>140 RecurrentSTelevation Invasive strategy Immediate Early invasive strategy with intent to perform invasive strategy within24hrs revascularisationbefore hospital discharge ](https://venus-llm-1258344701.cos-internal.ap-guangzhou.tencentcos.cn/userUpload/is-62e36cd9/2025-04-10/08893126-41bb-499d-af90-f3716e89abef/08893126-41bb-499d-af90-f3716e89abef.jpg?q-sign-algorithm=sha1&q-ak=AKID61g5D5fy1TjiRv84nEOHtFJ8gyzjCPL0&q-sign-time=1744240805%3B1744244405&q-key-time=1744240805%3B1744244405&q-header-list=host&q-url-param-list=&q-signature=3ec226e5d85b0355b57bc62e35ba69ae8ccf75e4) Figure 13 Timing of invasive management for NSTEACS. Abbreviations: ECG, electrocardiogram; GRACE, Global Registry of Acute Coronary Events; hs-cTn, high-sensitivity cardiac troponin; MI, myocardial infarction; NSTEACS, non-ST-segment elevation acute coronary syndromes.

3.3.4. Procedural considerations in NSTEACS Recommendations

|Recommendation| Strength of recommendation | Certainty O1 evidence | |---|---|---| |Recommendation| Strength of recommendation | Certainty O1 evidence | |||| |In people with NSTEACS|Strong|High| |undergoing an invasive||| |approach, radial access||| |is preferred to femoral||| | access, unless contraindicated.||| | In people with NSTEACS|weak|High| |undergoing an invasive||| |approach, consider||| |||| | intravascular imaging to guide PCI. |||

Evidence supporting the recommendations Radial access

Multiple RCTs and meta-analyses have shown a reduction in mortality $(1.6\%$ vs $2.1\%$ , HR 0.77, $95\%$ CI 0.63 – 0.95) and major bleeding ( $1.5\%$ vs $2.7\%,$ , OR 0.55, $95\%$ CI 0.45 – 0.67) with radial instead of femoral access in people with NSTEACS [ 303 – 307 ]. Therefore, unless precluded due to a lack of operator experience or other related contraindications, a radial ﬁ rst approach is recommended over femoral access.

Intravascular imaging-guided PCI

An intravascular imaging (IVI)-guided approach to PCI over standard angiography-guided PCI has been tested in multiple RCTs and meta-analyses, with a range of different complex person- and lesion-speci ﬁ c characteristics. A 2024 metaanalysis (22 RCTs, $\scriptstyle{\mathfrak{n}}=15,964$ ) found that IVI-guided PCI (optical coherence tomography and intravascular ultrasound (IVUS)), compared to angiography-guided PCI, reduced target lesion failure (RR 0.71, $95\%$ CI 0.63 – 0.80, $\mathsf{p}\!\!<\!\!0001$ ). This was driven by reductions in risks of cardiac death (RR 0.55, $95\%$ CI 0.41 – 0.75, $\mathsf{p}\!\!=\!\!0.001\!,$ ), target vessel MI (RR 0.82, $95\%$ CI 0.68 – 0.98; $\mathtt{p}{=}0.030,$ ) and target lesion repeat revascularisation (RR 0.72, $95\%$ CI 0.60 – 0.86, $\mathrm{p{=}}0.0002.$ ) [ 367 ]. IVI-guided PCI also reduced the risks of all MI (RR 0.83, $95\%$ CI 0.71 – 0.99; $\mathtt{p}{=}0.033)$ ) and all-cause death (RR 0.75, $95\%$ CI 0.60 – 0.93; $\mathrm{p{=}}0.0091$ ). Outcomes for optical coherence tomographyguided procedures were similar to IVUS-guided procedures.

From a 2023 meta-analysis of 32 RCTs (of which 19 were ACS trials), on subgroup analysis, the bene ﬁ t of IVI-guided over angiography-guided PCI was of similar or greater magnitude in people with ACS [ 368 ]. Of note, RCTs included in both meta-analyses had different inclusion criteria, and largely included more complex lesions (e.g. bifurcations, presence of calci ﬁ cation and/or long segment of disease), and people at higher risk (e.g. people with diabetes). Therefore, the recommendation for intracoronary imaging over angiography alone should not be applied to every PCI procedure.

Practice points

Women

' Use a radial- ﬁ rst approach where possible for coronary interventions in both women and men, as it is associated with reduced complications and improved outcomes. B Consider a routine invasive approach for women with NSTEACS, as it has demonstrated bene ﬁ ts. Do not overlook the disparity in care, as observational data show women are less likely than men to receive an invasive strategy or radial access [ 325 , 355 ].

Older adults

' Consider an invasive strategy over an initial conservative approach in older adults with NSTEACS if they do not have frailty, multimorbidity or cognitive dysfunction based on objective assessment. The evidence to consider is: B Of ﬁ ve trials on invasive management in older adults with NSTEACS (mostly ${\geq}75$ years), four found no bene ﬁ t in the primary endpoints, but one showed reduced MI and urgent repeat revascularisation with a routine invasive strategy [ 369 – 374 ]. B For older individuals with MI and multivessel disease, physiology-guided complete revascularisation showed bene ﬁ ts, although frailty data were not provided [ 375 , 376 ]. B Meta-analyses of mixed designs have shown a likely reduction in MI and recurrent revascularisation with an invasive strategy versus a conservative (medical management) approach. In addition, there is a survival bene ﬁ t in observational studies and a strong trend towards survival bene ﬁ t in randomised trials, at the cost of a higher risk of bleeding relative to a conservative strategy in older people with NSTEACS [ 376 – 378 ]. B A small trial of frail individuals aged over 70 years (mean age 86) with NSTEACS found no bene ﬁ t from an initial invasive approach [ 379 ]. ' Individualise treatment decisions for older adults, balancing the potential for improved outcomes with the risks of complications, especially bleeding.

First Nations peoples

' Ensure information about transfers or invasive management is provided with the assistance of First Nations health practitioners or Aboriginal liaison of ﬁ cers ' Communicate in the person ’ s preferred language and when required to enhance understanding and informed decision making. ' Recognise that First Nations peoples from regional areas are less likely to receive angiography than non-Indigenous counterparts [ 380 ]. ' Be vigilant of barriers to equitable care, including: B inadequate cultural competency among healthcare providers B perceptions about medicine compliance $\bigcirc$ delayed transfers to PCI-capable hospitals B insuf ﬁ cient family and community engagement by clinicians [ 68 ].

3.4. Antiplatelet Therapy in the Acute Phase

Recommendations

Recommendation Strength of Certainty of recommendation evidence In people with STEMI treated Strong Moderate with ﬁ brinolytic therapy, give dual antiplatelet therapy with aspirin and clopidogrel. In people with STEMI Strong High undergoing primary PCI and people with NSTEACS undergoing a routine invasive strategy, give dual antiplatelet therapy with aspirin and a potent $\mathrm{P}2\mathrm{Y}_{12}$ inhibitor (ticagrelor or prasugrel). In people with STEMI Strong High undergoing primary PCI and people with NSTEACS undergoing a routine invasive strategy for whom ticagrelor or prasugrel are contraindicated, and those receiving oral anticoagulation, give clopidogrel. In people with NSTEACS for Strong High whom a selective invasive strategy is planned, give ticagrelor or clopidogrel. In people with NSTEACS, Weak Moderate consider routine genotypic or platelet function guidance of $\mathrm{P}2\mathrm{Y}_{12}$ therapy. In people with NSTEACS, Weak Moderate consider de-escalation from potent $\mathrm{P}2\mathrm{Y}_{12}$ inhibitor to clopidogrel, but not during the ﬁ rst 30 days following an ACS event. In people with ACS with Strong High concomitant non-valvular atrial ﬁ brillation and CHA2DS2VA score ${>}1.$ , give aspirin and clopidogrel, together with a non-vitamin K oral anticoagulant.

|(continued).||| |---|---|---| |Recommendation| Strength of Certainty of recommendationnevidence || | In people with STEMI|Consensus|Consensus| |undergoing primary PCI or||| |those with NSTEACS||| |undergoing an invasive||| |||| | strategy, routine glycoprotein HIa/IIb inhibitor (GPI) is not ||| |recommended.|||

Evidence supporting the recommendations Aspirin

The bene ﬁ t of aspirin on outcomes following STEMI independently and synergistically with ﬁ brinolytic therapy was originally shown in the ISIS 2 study $\scriptstyle(\mathfrak{n}=17,187)$ ) [ 381 ]. A metaanalysis incorporating broader populations of people with MI (15 RCTs conducted before 1997; $\scriptstyle{\mathfrak{n}}=19,302$ ) found that, compared with placebo, aspirin reduces the risk of serious vascular events (vascular death, MI and stroke; OR 0.70, $95\%$ CI 0.64 – 0.77) [ 216 ]. The risk of haemorrhagic stroke is increased, while that of ischaemic stroke decreased, giving an overall reduction in all-stroke risk (OR 0.62, $95\%$ CI 0.33 – 0.91).

An RCT (n=25,086 with ACS) comparing high-dose aspirin (300 – 325 mg daily) with low-dose aspirin (75 – 100 mg daily) showed no signi ﬁ cant bene ﬁ t, with no difference in cardiovascular death, MI, stroke or major bleeding between groups at 30 days [ 382 ].

Platelet $P2Y_{12}$ inhibitor treatment with ﬁ brinolytic therapy In a large study enrolling 45,852 people with STEMI, clopidogrel added to aspirin reduced death, reinfarction or stroke by $9\%$ ( $95\%$ CI 3 – 14) when compared to aspirin alone [ 383 ]. In a trial of 3,491 people with STEMI randomised to clopidogrel or placebo at the time of ﬁ brinolysis, coronary patency improved and ischaemic endpoints were reduced among people receiving clopidogrel [ 384 ]. The loading dose has not been studied in older people and is therefore not recommended in people over 75 years.

One small prospective open-label randomised trial $(\mathtt{n}\!\!=\!\!335]$ ) comparing ticagrelor and clopidogrel at the time of ﬁ brinolysis found no difference in ischaemic MACE events but more minor bleeds with ticagrelor [ 385 ].

There was no difference in ischaemic or bleeding events in an RCT of 3,799 people randomised to ticagrelor or clopidogrel beyond 24 hours from ﬁ brinolysis [ 386 ]. Thus, people initially thrombolysed and given clopidogrel, then transferred to another centre for PCI may safely be switched to ticagrelor following PCI.

Platelet $P2Y_{12}$ inhibitor therapy in people with STEMI undergoing primary PCI

The preferred $\mathrm{P}2\mathrm{Y}_{12}$ inhibitors are ticagrelor or prasugrel as they have more rapid onset of action, greater potency and are superior to clopidogrel in clinical outcomes [ 387 , 388 ]. Prasugrel is contraindicated if the person is ${<\!60~\mathrm{kg}},\,{\geq}75$ years and/or has had a previous stroke/transient ischaemic attack. Clopidogrel should be given as the preferred $\mathrm{P}2\mathrm{Y}_{12}$ inhibitor in people with previous haemorrhagic stroke, on oral anticoagulants (OACs) or with moderate-to-severe liver disease.

The timing of $\mathrm{P}2\mathrm{Y}_{12}$ inhibitor administration in people with STEMI undergoing primary PCI has been studied in a meta-analysis (three RCTs, 14 observational studies, n=70,465) [ 389 ]. Pretreatment $\mathrm{(P2Y}_{12}$ inhibitor administration before angiography) compared to no pretreatment $\mathrm{(P2Y}_{12}$ administration during or immediately after PCI) did not result in reductions in all-cause mortality or major bleeding. Subgroup analysis found that $\mathrm{P}2\mathrm{Y}_{12}$ inhibitor pretreatment in the pre-hospital setting was associated with a reduction in MI, compared to no pretreatment (RR 0.73, $95\%$ CI 0.56 – 0.91, $\mathtt{p}{<}0.01,$ ). Therefore, in people with a working diagnosis of STEMI undergoing primary PCI, pretreatment with a $\mathrm{P}2\mathrm{Y}_{12}$ inhibitor may be considered. If pretreatment is not given, all people should receive a $\mathrm{P}2\mathrm{Y}_{12}$ inhibitor loading dose at the time of PCI (see Supplementary Material B3 ).

Platelet $P2Y_{12}$ inhibitor treatment in NSTEACS

Clopidogrel with aspirin reduced the composite of cardiovascular death, MI or stroke when compared with aspirin alone in 12,562 people with NSTEMI (RR 0.80, $95\%$ CI 0.72 – 0.90) [ 390 ]. As for people with STEMI, subsequent trials have shown that potent $\mathrm{P}2\mathrm{Y}_{12}$ inhibition with ticagrelor or prasugrel is preferred over clopidogrel in people with NSTEACS undergoing a routine invasive strategy [ 387 , 388 ]. Two RCTs have found that pretreatment with prasugrel at the time of diagnosis (before angiography) compared with treatment at the time of PCI following angiography did not reduce ischaemic events but did increase bleeding [ 391 ]. Similar results were reported from an analysis of the SWEDEHEART registry that included ticagrelor and clopidogrel in NSTEACS [ 392 ]. Therefore, $\mathrm{P}2\mathrm{Y}_{12}$ inhibitors can be withheld until the coronary anatomy is known and if coronary angiography can be performed within the time recommendations (section 2.6 Further Diagnostic Testing for People with Suspected ACS ).

Ticagrelor, but not prasugrel, was found to be superior to clopidogrel in people with NSTEACS managed without PCI. Therefore, prasugrel is not recommended in people who do not undergo PCI [ 388 , 393 ].

In the CURRENT-OASIS trial $\mathsf{(n e25,086)}$ ), a loading dose of $600\ \mathrm{mg}$ of clopidogrel followed by maintenance of $150~\mathrm{mg}$ showed no difference in ischaemic endpoints and a signi ﬁ cant increase in major bleeding (HR 1.24, $95\%$ CI 1.05 – 1.46) when compared against $300~\mathrm{mg}$ loading and $75~\mathrm{mg}$ maintenance [ 382 ]. There was, however, a bene ﬁ t in the subgroup of people who underwent PCI (HR 0.85, p=0.04). Therefore, double dose clopidogrel may be considered in these people [ 382 ].

An RCT of 4,018 people with ACS (ISAR REACT 5) randomised to either ticagrelor or prasugrel, of which $83\%$ received PCI, demonstrated an increase in death, recurrent MI and stroke, in people randomised to ticagrelor (HR 1.36, $95\%$ CI 1.09 – 1.70) with no signi ﬁ cant differences in bleeding [ 394 ]. This study has been criticised because of its open-label design, high rate of study discontinuation during follow-up $(30\%$ in both arms) and primary reliance on phone call follow-up rather than study visits to ascertain the components of the primary outcome [ 395 ].

Guiding therapy based on genetic or platelet function testing Approximately $30\%$ of people do not respond to clopidogrel. This is thought to be the reason for the improved ef ﬁ cacy and increased bleeding of the more potent $\mathrm{P}2\mathrm{Y}_{12}$ antagonists when compared with clopidogrel. Selection of therapy based on response to clopidogrel (as indicated by either genotyping or platelet function testing) has not shown a consistent bene ﬁ t. This is likely because these strategies do not provide a comprehensive assessment of platelet responsiveness, together with differences in trial design and lack of power [ 396 – 398 ].

A network meta-analysis of 15 RCTs including 61,898 people with ACS demonstrated that therapy guided by genotyping of clopidogrel resistance compared to potent $\mathrm{P}2\mathrm{Y}_{12}$ inhibitor therapy appeared to provide the best balance between less bleeding with clopidogrel and fewer ischaemic events with potent $\mathrm{P}2\mathrm{Y}_{12}$ inhibitors ticagrelor and prasugrel [ 396 , 399 , 400 ]. However, genotyping is not readily available in Australia, and further research is required to ascertain its role in the Australian setting. In addition, when platelet function-guided escalation is used, people need to be on clopidogrel initially to demonstrate non-responsiveness. This may place people with ACS at increased risk.

De-escalation of potent $P2Y_{12}$ inhibitor therapy

Three major RCTs investigated the safety and ef ﬁ cacy of intentional de-escalation of potent $\mathrm{P}2\mathrm{Y}_{12}$ inhibitor therapy following an ACS [ 401 – 403 ]. One single centre study compared the impacts of de-escalation from ticagrelor or prasugrel to clopidogrel, with no switching of therapies $\mathrm{(n{=}646)}$ ). The primary composite outcome was cardiovascular death, urgent revascularisation, stroke and bleeding (Bleeding Academic Research Consortium scale ${\geq}2$ ) [ 403 ]. There was net bene ﬁ t in the de-escalated group (HR $95\%$ CI 0.48 (0.34 – 0.68)), driven by lower bleeding risk and no difference in ischaemic endpoints.

A multi-centre trial randomised people to ticagrelor and aspirin or intentional de-escalation to clopidogrel and aspirin after one month $\scriptstyle(\mathbf{n}=2,697)$ . The primary endpoint was a composite of cardiovascular death, MI, stroke, or bleeding (Bleeding Academic Research Consortium scale ${\geq}2.$ ) at 12 months. There was a demonstrated $4.6\%$ absolute risk bene ﬁ t (HR $95\%$ CI 0.55 (0.40 – 0.76)) in people undergoing deescalation, also driven by reductions in bleeding risk [ 401 ].

Similar results were observed in another multi-centre trial using prasugrel $10~\mathrm{mg}$ daily for the ﬁ rst month, followed by randomisation to either reduced dose prasugrel (5 mg daily) or standard dosing $\mathbf{(n{=}2,338)}$ ); (HR $95\%$ CI 0.70 (0.52 – 0.92)) [ 402 ].

In all three studies, de-escalation did not occur until more than one month following discharge, and therefore earlier de-escalation cannot be recommended at this time [ 28 ]. Additionally, de-escalation occurred without giving a loading dose of clopidogrel upon switching.

Two of the studies were conducted in primarily east Asian populations, in whom ethnic differences in both response to clopidogrel and outcomes following PCI have been identiﬁ ed when compared to Caucasian populations [ 401 , 402 , 404 ].

Combining oral antiplatelet and oral anticoagulant therapy in ACS

In people with ACS requiring anticoagulation for nonvalvular atrial ﬁ brillation, studies with direct oral anticoagulants (DOACs) have shown that after an initial period (1 – 4 weeks) of triple therapy (aspirin in addition to a $\mathrm{P}2\mathrm{Y}_{12}$ antagonist and an OAC), lower bleeding rates are seen with DOACs and clopidogrel compared to warfarin with continued DAPT (section 4 Recovery and Secondary Prevention ) [ 405 – 407 ].

Discontinuing $P2Y_{12}$ inhibition prior to cardiac surgery for ACS

Based on pharmacokinetic data, the safe windows for cessation of $\mathrm{P}2\mathrm{Y}_{12}$ inhibitors prior to non-emergency cardiac surgery are 5 days for clopidogrel, 3 days for ticagrelor and 7 days for prasugrel [ 408 ].

Intravenous glycoprotein IIb/IIIa inhibitors

Routine use of IV GPI in people undergoing primary PCI confers no bene ﬁ t and signi ﬁ cantly increases bleeding risk [ 409 , 410 ]. In term of intracoronary administration, a small RCT $\scriptstyle(\mathbf{n}=162)$ ) of intracoronary tiro ﬁ ban versus heparin alone in select people with STEMI who had TIMI ${<}3$ following post-dilation showed signi ﬁ cantly greater reperfusion $(32\%$ vs $10\%,$ $\mathrm{p{=}}0.001.$ ), and reduction of in-hospital in-stent thrombosis and non-fatal MI [ 411 ]. Similarly, a meta-analysis of 10 RCTs (n=1,590) found improved outcomes with intracoronary administration of GPI compared with IV administration, in terms of TIMI, target vessel revascularisation and short-term mortality. However, conclusions could not be drawn about mid and long-term outcomes [ 412 ].

Trials using GPI in people with NSTEACS showed a reduction in ischaemic events at a cost of increased bleeding when compared to heparin alone. However, all were conducted prior to the routine use of potent $\mathrm{P}2\mathrm{Y}_{12}$ inhibitors and later generation stenting [ 413 , 414 ]. Contemporary studies have shown that upstream use of GPI increases bleeding and transfusion requirements without offering clinical bene ﬁ t [ 414 ]. In people not undergoing an invasive strategy, GPIs were not shown to reduce death or recurrent MI compared with placebo [ 415 ].

Practice points ' Aspirin: In the event of aspirin sensitivity, risk assessment and consideration of desensitisation should be made using a standardised protocol to achieve adequate antithrombotic therapy [ 416 ]. ' Selection of platelet $\mathbf{P2Y_{12}}$ inhibitor therapy: Prasugrel has Therapeutic Goods Administration (TGA) approval but is not currently available in Australia. Exercise care regarding timing and dosing of $\mathrm{P}2\mathrm{Y}_{12}$ inhibitors when switching between these agents to ensure their effectiveness is maintained and the bleeding risk is minimised. For guidance on switching strategies, see Supplementary Material B3 . ' Timing of platelet $\mathbf{P2Y_{12}}$ inhibitor administration in STEMI: Deferring the administration of the $\mathrm{P}2\mathrm{Y}_{12}$ inhibitor until after the coronary anatomy is known is reasonable when the diagnosis of STEMI is uncertain or if there is a clinical suspicion of need for urgent cardiothoracic surgery (e.g. left main ischaemia pattern on ECG). ' Timing of platelet $\mathbf{P2Y_{12}} $ inhibitor initiation in NSTEACS: Decisions regarding timing of initiation of $\mathrm{P}2\mathrm{Y}_{12}$ inhibitor in relation to invasive angiography may be institution-dependent and need to be clearly de ﬁ ned and communicated effectively between emergency and inpatient services. ' Combining $\mathbf{P2Y_{12}}$ inhibition with anticoagulation: In people with ACS with an indication for vitamin K antagonist (e.g. mechanical heart valve), use aspirin with clopidogrel rather than ticagrelor or prasugrel to reduce the risk of bleeding. Target international normalised ratios (INRs) should be at the lower therapeutic range (e.g. 2.5 – 3 for mechanical mitral valves). ' IV GPI administration: Bailout GPI may be considered in people at high ischaemic risk such as high thrombus burden, no- ﬂ ow or slow- ﬂ ow. ' Discontinuing platelet $\mathbf{P2Y_{12}}$ inhibitor prior to CABG: In people with NSTEACS with planned CABG, do not administer $\mathrm{P}2\mathrm{Y}_{12}$ inhibitor within 3 days of surgery for ticagrelor, 5 days for clopidogrel or 7 days for prasugrel. ' Selection of GPI therapy: Tiro ﬁ ban is the only GPI marketed in Australia, while epti ﬁ batide and abciximab can be obtained through the TGA ’ s Special Access Scheme. ' Discontinuing IV GPI in thrombocytopenia: Glycoprotein IIb/IIIa inhibition is not recommended in people with thrombocytopenia (platelet count ${<}150{,}000/\mathrm{{mL})}$ ) and should be suspended immediately if platelet count falls below this level or drops by $50\%$ or more from baseline. ' Discontinuing IV GPI prior to CABG: In people undergoing CABG, discontinuation of short-acting GPI (epti ﬁ - batide and tiro ﬁ ban) for four hours and abciximab for 12 hours before surgery is recommended to reduce the risk of bleeding and transfusion [ 417 – 419 ].

3.5. Anticoagulant Therapy in the Acute Phase

Recommendations

|Recommendation|Strength of|| |---|---|---| ||recommendation| Certainty of evidence | ||| Moderate | | People treated with|Strong|| |fibrinolytic therapy||| |should receive||| | anticoagulation||| |(unfractionated heparin||| |or enoxaparin).||| | People undergoing| Strong| Moderate| |primary PCI should|| Moderate| |receive anticoagulation||| |(unfractionated heparin||| | or bivalirudin).||| |People with NSTEACS| Strong|| |should receive||LOW| |anticoagulation||LOW| |(unfractionated||| |heparin, enoxaparin, or||| |fondaparinux).|||

Evidence supporting the recommendations

Anticoagulant treatment with ﬁ brinolytic therapy

The GUSTO trial $(\mathsf{n}{=}40{,}021)$ ) of people with STEMI receiving ﬁ brinolysis with tissue plasminogen activator (tPA) and IV heparin, or streptokinase and either IV or subcutaneous heparin, or combination of both ﬁ brinolytic agents and IV heparin showed the lowest mortality among those receiving tPA and IV heparin [ 420 ]. In the ASSENT-3 trial, of people with STEMI receiving ﬁ brinolysis with tenecteplase, enoxaparin, $30~\mathrm{mg\IV}$ followed by $1\ \mathrm{mg/kg}$ twice daily $\mathrm{(n{=}2,040)}$ ) resulted in fewer ischaemic endpoints than IV heparin $\mathrm{(n{=}2,038)}$ ) (RR 0.74, $95\%$ CI 0.63 – 0.87) [ 421 ].

Anticoagulant therapy with primary PCI

Unfractionated heparin (UFH) (in combination with DAPT) has been the standard of care for many decades in people undergoing primary PCI. RCTs comparing bivalirudin and heparin prior to 2022 reported no difference in ischaemic endpoints but less bleeding with bivalirudin [ 312 , 422 , 423 ]. However, these RCTs are dif ﬁ cult to interpret in today ’ s clinical practice due to heparin historically being combined with routine (instead of bailout) GPI and low rates of radial access.

The unblinded BRIGHT-4 RCT $\mathrm{(n{=}6,016)}$ published in 2022 demonstrated a bene ﬁ t of bivalirudin over UFH (0.7 units/kg) in primary PCI, with a reduction in 30-day total mortality (89 vs 118 people, $\mathsf{p{=}0.04},$ ) and major bleeding (5 vs 24 people, $\mathtt{p}{=}0.001\mathtt{,}$ ), with high $(93\%)$ radial access use and bailout (not routine) GPI [ 424 ]. Bivalirudin can therefore be

considered instead of UFH in people undergoing primary PCI for STEMI, factoring in differences in cost and experience with administration. Bivalirudin should be used instead of UFH in people with heparin-induced thrombocytopenia.

Anticoagulant therapy in NSTEACS

Three small studies enrolling a total of 847 people showed that UFH was associated with a $62\%$ reduction in trialde ﬁ ned MACE (OR 0.38, $95\%$ CI 0.15 – 0.97) with no increase in major bleeding at 5 days when compared to placebo [ 425 – 427 ]. Although these trials precede the use of early invasive management and availability of troponin assays, they form the basis for recommending anticoagulation therapy in people at high and intermediate risk of ACS.

A meta-analysis of ﬁ ve RCTs comparing UFH with low molecular weight heparin (LMWH) on background therapy with aspirin (n=11,838) showed LMWH to be associated with a reduction in trial-de ﬁ ned MACE (OR 0.81, $95\%$ CI 0.69 – 0.95) with no signi ﬁ cant increase in bleeding [ 428 ]. These studies were conducted before the availability of troponin assays, with very low rates of coronary angiography. This metaanalysis did not include the largest trial comparing UFH to LMWH (n=9,978) which enrolled people on a background of DAPT with high rates of early coronary angiography $(92\%)$ and GPI use $(57\%)$ [ 429 ]. There was no difference in the ischaemic endpoint of death and MI, but a signi ﬁ cant increase in major bleeding in people receiving LMWH (HR 1.21, $95\%$ CI 1.05 – 1.40) which was commonly femoral access-related.

Contemporary meta-analyses of UFH with bivalirudin have shown no signi ﬁ cant bene ﬁ t for ischaemic outcomes, especially with the growing preference for radial access and fewer bleeding events [ 430 ].

A pooled analysis of two trials $\mathsf{(n{=}20{,}378)}$ ) comparing fondaparinux with LMWH in people on DAPT showed a halving of major bleeding at 9 days (HR 0.52, $95\%$ CI 0.44 – 0.62) with no difference in trial-de ﬁ ned MACE. There were high rates of angiography in these trials, but the median time to angiography was long (2.5 days in the larger OASIS-5 trial) [ 428 , 431 ].

Practice points

Anticoagulant treatment with ﬁ brinolytic therapy

' Omit IV bolus of enoxaparin in people ${>}75$ years receiving ﬁ brinolysis and enoxaparin. ' Enoxaparin is recommended over UFH unless there is severe kidney impairment (estimated glomerular ﬁ ltration rate (eGFR) , 30 mL/min) [ 432 , 433 ].

Anticoagulant therapy with primary PCI

' In people requiring PCI with a history of heparin-induced thrombocytopenia, consider bivalirudin as an alternative to UFH. Outcomes with bivalirudin are optimised when followed by a high dose post-PCI infusion $(1.75~\mathrm{m}\mathrm{g}/\mathrm{kg}/$ hr) for 2 – 4 hours [ 434 ].

Anticoagulant therapy in NSTEACS

' In people treated with fondaparinux undergoing coronary angiography and/or PCI, standard dose UFH is

recommended at the time of the procedure to reduce the risk of guiding-catheter thrombosis [ 390 , 431 ]. ' In people receiving LMWH in whom femoral access for coronary angiography is planned, it is common practice to omit the morning dose of enoxaparin to minimise accessrelated bleeding complications [ 435 ]. ' Parenteral anticoagulants can be ceased following PCI. In people who do not undergo PCI, UFH may be ceased at 48 hours and fondaparinux or LMWH at 6 days following presentation in the absence of other indications [ 429 , 431 ].

Anticoagulant use in people already receiving warfarin or DOACs

There are no randomised studies evaluating strategies for early anticoagulation in people with ACS who are already taking warfarin or DOACs. Guidance for these people is derived from expert opinion [ 436 ].

' In people with continued indications for oral anticoagulants (atrial ﬁ brillation and CHA2DS2VA score ${>}1$ , mechanical heart valves, or recurrent venous thromboembolism), do not cease this treatment.

' In people with NSTEACS undergoing invasive management, wherever possible a brief washout period from the effects of OACs is desirable. This is to reduce the risk of potential bleeding complications among those who may require femoral access or resulting from additional anticoagulation during the procedure. This can be 24 hours for people on DOACs with normal renal function and 48 hours for those with impaired renal function. For people on warfarin, an INR of ${<}2.0$ is recommended when using the radial approach and ${<}1.5$ when using the femoral approach.

3.6. Acute Management of ACS with Cardiac Arrest and/or Cardiogenic Shock

3.6.1. ACS with cardiac arrest Recommendations

|Recommendation|Strength of|| |---|---|---| ||recommendation| Certainty of evidence | ||Strong|| | In people with return of||LOW| |spontaneous circulation||| | after resuscitated||| |cardiac arrest and||| | persistent STE on ECG, perform emergency ||| | reperfusion.||| ||||

|(continued).||| |---|---|---| |Recommendation| Strength of recommendation | Certainty of evidence | | In haemodynamically| Strong || | stable people with||Moderate| |resuscitated cardiac||| |arrest and no STE on||| |ECG, do not perform||| | routine emergency||| | coronary angiography.|||

Evidence supporting the recommendations

Cardiac arrest in the context of STEMI is a common cause of early death and usually occurs out of hospital [ 437 ]. In people with resuscitated cardiac arrest and an ECG consistent with STEMI, reperfusion with primary PCI improves survival [ 438 – 440 ].

In the absence of STE on ECG, a meta-analysis of seven RCTs $\scriptstyle(\mathfrak{n}=1,544)$ found no survival or neurological bene ﬁ t of early or immediate angiography over a delayed angiography strategy in people with resuscitated cardiac arrest [ 441 ]. It is important to note that people with cardiogenic shock were excluded from these trials, hence emergency angiography in the presence of haemodynamic instability may be considered.

Practice points

' In people with STEMI and resuscitated cardiac arrest, primary PCI is the preferred reperfusion strategy. Fibrinolysis may be considered if primary PCI is unavailable. However, evidence is lacking with potential for harm in cardiac arrest that is refractory, prolonged and/or traumatic [ 17 , 288 , 442 ]. ' In people with STEMI and resuscitated cardiac arrest, the decision for primary PCI should factor in treatment futility. For instance, advanced age, presence of severe metabolic acidosis and/or no return of spontaneous circulation for an extended period are associated with a low likelihood of meaningful long-term survival [ 443 ].

3.6.2. ACS with cardiogenic shock Recommendations

|Recommendation|Strength of| Certainty of evidence | |---|---|---| ||recommendation|| |In people with ACS and|Strong|Moderate| |cardiogenic shock, perform||| |PCI of the IRA only.|||

|(continued).||| |---|---|---| |Recommendation| Strength of recommendation | Certainty of evidence High | ||| Certainty of evidence High | | In people with ACS and|Strong| Certainty of evidence High | |cardiogenic shock, routine|| Certainty of evidence High | |insertion of an intra-aortic||| |balloon pump is not ||| |recommended.||| | In people with ACS and|Strong|Moderate| |cardiogenic shock, routine||| |venoarterial extracorporeal||| | membrane oxygenation is||| | not recommended.||| |||| | In select people with|Weak|Moderate| | STEMI and cardiogenic||Moderate| | shock, consider left ventricular assist devices. |||

Evidence supporting the recommendations

Treatment of MVD in ACS with cardiogenic shock

In people with NSTEACS, MVD and cardiogenic shock, RCTs have studied the bene ﬁ t of IRA-only PCI versus routine PCI of IRA and non-IRA lesions at the time of initial angiography. The CULPRIT-SHOCK trial included approximately $40\%$ of enrolled people with a NSTEMI $\mathtt{(n=706)}$ ). At 30 days, the composite primary endpoint of death or renal replacement therapy occurred in $45.9\%$ of the IRA-only PCI group versus $55.4\%$ of the multivessel PCI group (RR 0.83, $95\%$ CI 0.71 – 0.96) [ 444 ]. The difference was driven by signi ﬁ cantly lower mortality in the IRA-only PCI group.

In people with STEMI complicated by cardiogenic shock, a single RCT and observational studies have found that routine PCI of non-IRAs at the time of primary PCI was associated with increased risk of death and renal failure [ 444 – 446 ]. Therefore, in the presence of cardiogenic shock, PCI of non-IRAs should not be performed at the time of the index procedure, but staged PCI should be considered for complete revascularisation.

Haemodynamic support devices in MI and cardiogenic shock In people with MI and cardiogenic shock, routine insertion of an intra-aortic balloon pump has been associated with an increased risk of bleeding with no impact on survival or infarct size [ 447 – 449 ].

In the ECLS-SHOCK trial ( $\mathrm{{(n{=}417}}$ people with AMI and cardiogenic shock, planned for urgent revascularisation), early venoarterial extracorporeal membrane

oxygenation (VA-ECMO) did not reduce 30-day mortality compared with usual care (RR 0.98, $95\% $ CI 0.80 – 1.19, $\mathtt{p}{=}0.81$ ) [ 450 ]. Early VA-ECMO was associated with higher rates of peripheral vascular complications requiring interventions (RR 2.86, $95\% $ CI 1.31 – 6.25), compared with usual care.

A meta-analysis (four RCTs, $\scriptstyle{\mathfrak{n}}=567$ ) did not ﬁ nd a reduction of 30-day mortality with the early use of VAECMO (OR 0.93; $95\%$ CI 0.66 – 1.29), with higher major bleeding (OR 2.44, $95\%$ CI 1.55 – 3.84) and peripheral ischaemic vascular complications (OR 3.53, $95\% $ CI 1.70 – 7.34), compared with standard care [ 451 ]. There were no prespeci ﬁ ed subgroups where any bene ﬁ t of VA-ECMO could be seen.

The DanGer Shock trial recruited people with STEMI and cardiogenic shock $(\mathtt{n}\!\!=\!\!360)$ ), excluding those with cardiac arrest or overt right heart failure. The study found that using percutaneous left ventricular assist devices (the microaxialﬂ ow-pump, or Impella) reduced all-cause death compared with standard care $(45.8\%$ vs $58.5\%$ , HR 0.74, $95\%$ CI 0.55 – 0.99, $\mathsf{p{=}0.04}$ ) [ 452 ]. The survival bene ﬁ t came at a cost of increased bleeding and vascular complications ( $(24\%$ vs $6.2\%,$ HR 4.74, $95\%$ CI 2.36 – 9.55). In addition to haemodynamic evidence of shock, people enrolled had left ventricular impairment $(\mathord{<}45\%.$ , median left ventricular ejection fraction [LVEF] $25\%$ ) and elevated arterial lactate $(>\!2.5\,\mathrm{\mmol}/\mathrm{L},$ median 4.6 mmol/L). People with right ventricular impairment and those with resuscitated out-of-hospital cardiac arrest who were comatose (Glascow Coma Scale ${\leq}8.$ ) were excluded.

Practice points

' Consider intra-aortic balloon pump in select cases – for example, where there are mechanical complications (ventricular septal rupture, mitral regurgitation or free ventricular wall rupture) – and/or as bridging to heart transplant or left ventricular assist devices. ' Consider mechanical support including VA-ECMO on a case-by-case basis, as rescue or bridging therapy. Such support can also be considered for treatment of intractable ventricular tachyarrhythmias, in consultation with a multidisciplinary team. ' Consider left ventricular assist devices in people with STEMI and cardiogenic shock on a case-by-case basis, given the selected population enrolled and the complication rate in the DanGer Shock trial. ' In people with ACOMI and cardiogenic shock, where PCI is unavailable, consider ﬁ brinolysis with a plan for subsequent angiography (see recommendations in section 3.2 Ongoing Management of Fibrinolytic-Treated People ) [ 453 ].

3.7. Treatment for ACS with Multivessel Disease without Cardiogenic Shock

Recommendations

|Recommendation| Strength of recommendation | Certainty of evidence | |---|---|---| |||| | In haemodynamically |Strong|High| |||| |stable people with||| | STEMI and MVD,||| | perform PCI of||| |suitable non-IRA(s).||| | Consider performing|Weak| Moderate| |PCI of the non-IRA at||| |the time of primary||| | PCI or within 19 days||| |of the index||| | procedure.||| | In people with STEMI||Consensus| |and MVD, routine||| | invasive physiology||| | assessment (e.g.||| |fractional flow reserve||| |[FFR]) to evaluate||| | non-IRA severity is||| | not recommended.||| | In people with|Weak| LOW | |NSTEACS and non-||| | complex MVD,||| | consider routine PCI||| |of non-IRA in the||| | same setting.||| |||| | In people with|weak|LOW| |NSTEACS and MVD,||| | consider invasive||| | physiology||| |assessment (e.g. FFR)||| |to evaluate non-IRA||| |severity.|||

Evidence supporting the recommendations Treatment of MVD in STEMI

In people with STEMI, MVD and without cardiogenic shock, RCTs have shown a bene ﬁ t of complete revascularisation over IRA-only PCI with a reduction in cardiac death, recurrent MI and repeat revascularisation [ 320 , 454 – 467 ].

The MULTISTARS-AMI trial recruited people with STEMI and MVD to undergo immediate (at the time of index procedure, $\mathrm{n{=}418}$ ) versus staged (median 28 days, range 19 – 45 days after index procedure, $\mathrm{n{=}}422$ ) PCI of the non-IRA. Immediate revascularisation was superior to staged PCI with lower death, non-fatal MI, stroke, unplanned ischaemiadriven revascularisation and heart failure hospitalisation (RR 0.52, $95\%$ CI 0.38 – 0.72, p , 0.001) [ 468 ]. This trial suggests

that complete revascularisation during the index procedure is both safe and superior to outpatient staged PCI. It is unknown if immediate non-IRA PCI is superior to inpatient staged PCI (or PCI performed within 19 days).

It should be noted that only a third of people in these trials had triple-vessel disease. People with left main disease, chronic total occlusions or planned for surgical revascularisation were largely excluded. Therefore, in people with complex MVD, CABG may be the appropriate complete revascularisation strategy (section 3.8 Coronary Artery Bypass Graft Surgery in ACS ).

Treatment of MVD in NSTEACS

While complete revascularisation in STEMI is bene ﬁ cial, currently there has been no dedicated trial comparing complete revascularisation versus PCI of the IRA only in people with NSTEACS. NSTEACS presents unique clinical challenges for management of MVD, including dif ﬁ culty identifying the IRA lesion and a heterogenous pathophysiology.

A meta-analysis of observational studies in people with NSTEACS (15 studies, $\scriptstyle{\mathfrak{n}}=171,279$ ) found people who underwent multivessel revascularisation had higher short-term risk, but lower long-term MACE (OR 0.76, $95\%$ CI 0.61 – 0.93), all-cause death (OR 0.83, $95\%$ CI 0.71 – 0.97) and repeat revascularisation (OR 0.62, $95\%$ CI 0.42 – 0.90) [ 469 ].

Invasive physiology to evaluate the non-IRA in STEMI or NSTEACS and MVD

Several RCTs have compared a physiology-guided approach (mostly using FFR) to an angiography-alone approach in people with STEMI and MVD. Meta-analyses have not shown an overall bene ﬁ t of FFR-guided complete revascularisation in STEMI with MVD. Some have shown that angiography-guided complete revascularisation is associated with a lower risk of all-cause death and new MI compared with FFR-guided PCI [ 467 , 470 , 471 ]. The COMPLETE RCT demonstrated a clear bene ﬁ t of complete revascularisation in people with STEMI and MVD, even without a physiology-guided approach in most cases [ 456 ]. Therefore, in people with STEMI and MVD, the decision to undertake PCI of the non-IRA can be based on angiographic severity alone.

In people with NSTEACS and MVD, physiology assessment may be of more value. Several RCTs have speci ﬁ cally compared a physiology-guided approach to an angiographyguided approach in treatment of the non-IRA. The overall evidence supports physiology or FFR as being reliable for non-IRA lesion estimation in NSTEACS and that FFR-guided PCI results in more people being treated medically, compared with angiography-guided PCI [ 472 , 473 ]. However, the results have been con ﬂ icting regarding outcomes. The FLOWER-MI trial (n=1,171) showed no difference in clinical outcomes of FFR-guided versus angiography-guided PCI of the non-IRA [ 474 ]. The FRAME-AMI trial showed a reduction in MACE with FFR-guided versus angiography-guided non-IRA PCI. However, a limitation was that the trial was terminated early due to slow recruitment, with only $43\%$ $\mathrm{(n{=}562)}$ ) of the planned sample size enrolled [ 475 ].

![PeoplewithACSwithsuccessfulPCloftheIRA withangiographicstenosisinatleastonenon-IRA (vessel ≥2.25 mm) Cardiogenic shock STEMI NSTEACS DonotperformroutinePCl of the Performcomplete Consider complete non-IRA at the index procedure revascularisation.Early (at time revascularisation, either at ofindexprocedure orwithin index procedure or staged. 19days)PCIofthenon-IRAis Considerfunctionalinvasive superiortolaterstagedPCl testing (e.g. FFR) in intermediate(50-70%) Staged complete angiographiclesions revascularisation ](https://venus-llm-1258344701.cos-internal.ap-guangzhou.tencentcos.cn/userUpload/is-62e36cd9/2025-04-10/c1341568-a584-46e6-a7ab-b061069dfdcb/c1341568-a584-46e6-a7ab-b061069dfdcb.jpg?q-sign-algorithm=sha1&q-ak=AKID61g5D5fy1TjiRv84nEOHtFJ8gyzjCPL0&q-sign-time=1744240805%3B1744244405&q-key-time=1744240805%3B1744244405&q-header-list=host&q-url-param-list=&q-signature=1e88c8ed742dd06f8e89e7813d1edc4fb6df0ed9) Figure 14 Management of multivessel disease in people with ACS. Abbreviations: ACS, acute coronary syndromes; FFR, fractional ﬂ ow reserve; IRA, infarct-related artery; NSTEACS, non-STsegment elevation acute coronary syndromes; PCI, percutaneous coronary intervention; STEMI, ST-segment elevation myocardial infarction.

In older people with MI and MVD, physiology assessment may be of bene ﬁ t. The FIRE trial (n=1,445) included people ${\geq}75$ years with MI and MVD (median age 80 years, $65\%$ NSTEMI, $35\% $ STEMI). Findings showed FFR or angiography-derived quantitative ﬂ ow ratio guided complete revascularisation versus IRA-only PCI resulted in a signi ﬁ cant reduction in the composite endpoint of death, MI, stroke or revascularisation at one year (HR 0.73, $95\%$ CI 0.57 – 0.93, $\mathtt{p}{=}0.01.$ ). This was driven by reductions in cardiovascular death and MI (HR 0.64, $95\%$ CI 0.47 – 0.88), with no difference in safety outcome and similar ef ﬁ cacy in STEMI and NSTEMI [ 375 ]. Refer to Figure 14 for guidance on management of multivessel disease in people with ACS.

Practice points

Treatment of non-IRAs

' In people with STEMI and MVD, with unknown renal function, inpatient PCI as a staged rather than immediate procedure, may be preferable if complex MVD is present or operator fatigue precludes same setting multivessel PCI. ' In people with NSTEMI and MVD, timing for complete revascularisation should consider factors such as the presence of cardiogenic shock, lesion complexity and risk of contrast nephropathy. ' While a bene ﬁ t of FFR-guided over angiography-guided complete revascularisation has not been conclusively shown, it is reasonable to use FFR in intermediate $(50{-}69\%)$ ) non-infarct-related stenoses [ 471 ].

' In people with ACS and complex MVD, a multidisciplinary heart team approach to the revascularisation strategy is recommended. Management of people with ACS and complex MVD should be guided by multidisciplinary heart team discussions incorporating person-based (e.g. age, frailty, infarct size, personal preference) and lesion-based (e.g. location, severity and complexity) factors.

3.8. Coronary Artery Bypass Graft Surgery in ACS

Recommendations

|Recommendation|Strength of| Certainty of evidence | |---|---|---| |||| | In people with STEMI,|Strong|LOW| |mechanical||| | complications and||| |mitral valve disease||| |(e.g. ventricular septal||| |rupture, mitral valve||| |insufficiency because of||| |papillary muscle||| |infarction or rupture, or||| |free wall rupture),||| |perform CABG at the||| |time of surgery.|||

Evidence supporting the recommendations

Peri-operative mortality after mechanical complications of STEMI remains high [ 476 ]. Few percutaneous or medical treatments are available and urgent surgery most often remains the best option. A haemodynamically unstable person may require interim mechanical circulatory support. Performing CABG at the time of surgery for a mechanical complication of STEMI is based on small retrospective series with no randomised trial data [ 477 ].

Practice points

' In people with STEMI where PCI cannot be performed, consider emergency CABG if there is ongoing ischaemia and a large area of jeopardised myocardium. ' Overall, $4–10\%$ of people with NSTEACS will require CABG [ 478 ]. Factors that should be considered when deciding between PCI and CABG are the same as for people presenting electively. These include comorbidities, ﬁ tness for major surgery, and coronary anatomy. A multidisciplinary team should be involved in decision making. ' In people with ACS and MVD where CABG has been chosen as the complete revascularisation strategy, performing CABG at day one to seven (compared to day zero or ${>}7$ days) after diagnosis has lowest risk of mortality [ 479 ]. ' In people with ongoing ischaemia or haemodynamic instability with an indication for CABG, do not delay urgent surgery due to antiplatelet exposure.

3.9. Treatment for Spontaneous Coronary Artery Dissection

Recommendations

|Recommendation| Strength of|| |---|---|---| ||recommendation| Certainty of evidence | |||| | In people with ACOMI|Consensus|| |due to SCAD but who||| |are otherwise stable,||| |routine||| |revascularisation is not||| | recommended. ||| | In people with SCAD|Weak|VeryLow| |and haemodynamic||| |instability and/or||| |ongoing ischaemia,||| |consider selective||| |revascularisation.|||

Evidence supporting the recommendations

As there are no RCTs to guide therapy, recommendations in SCAD are based on observational studies or expert opinion [ 480 ]. Intervention is challenging and routine revascularisation is not recommended as it has been associated with several complications. These include iatrogenic dissection, wiring of the false lumen, propagation of the intramural haematoma, acute vessel closure and stent or graft failure [ 481 – 483 ]. However, in a subgroup of people with SCAD who have signi ﬁ cant ongoing ischaemia and haemodynamic compromise, urgent revascularisation with PCI or CABG may be required [ 484 – 487 ].

3.10. Myocardial Infarction with Non-Obstructive Coronary Arteries

In people with MINOCA, it is important to exclude alternative diagnoses [ 488 ]. Consider cardiac MRI in all people with MINOCA where the underlying cause is not obvious. Once the underlying cause has been established, manage people with MINOCA according to relevant disease-speci ﬁ c guidelines [ 27 ]. In all people with evidence of coronary atherosclerotic disease and/or risk factors, consider initiating secondary prevention measures (even if the underlying cause of MINOCA cannot be determined) [ 28 ].

3.11. Myocardial Infarction due to Oxygen Supply/Demand Mismatch without Acute Coronary Occlusion

No trials have examined the bene ﬁ ts of a routine invasive strategy in people with MI due to oxygen supply/demand mismatch without acute coronary occlusion [ 489 ]. Whether competing risks from non-cardiac conditions obscure the bene ﬁ ts of invasive management – and at what level of competing risk this occurs – remains uncertain. All available evidence demonstrates that people with MI due to oxygen supply/demand mismatch without acute coronary occlusion experience higher all-cause mortality than people with MI with acute coronary occlusion. This is, in part, related to associated non-coronary competing risks [ 489 ]. In the absence of any trial evidence, angiography with a view to revascularisation may be considered if there is ongoing ischaemia or haemodynamic compromise despite adequate treatment of the underlying acute stressors (section 3.1.3 Administration of ﬁ brinolytic therapy and Table 9 ).

3.12. Echocardiography

Left ventricular (LV) dysfunction is an important determinant of prognosis following ACS and its detection should guide further evidence-based therapies [ 490 ]. Echocardiography to evaluate regional and global LV function, and to identify other cardiac pathology, should be performed

during hospitalisation. If echocardiography is not possible, consider other aspects suggestive of LV dysfunction, including clinical signs/symptoms, and ECG, chest X-ray and biomarker features [ 490 ].

3.13. Duration of Cardiac Monitoring

Cardiac monitoring plays a pivotal role as an adjunct therapy in the management of ACS. Continuous cardiac monitoring has become a ﬁ rmly embedded standard of practice despite the absence of evidence from RCTs [ 491 ]. Clinical assessment for the risk of life-threatening arrhythmias should be individualised based on known associated risk factors: arrhythmias, ongoing symptoms, reduced LV function (LVEF ${<}40\%$ ), failed coronary reperfusion, haemodynamic instability, and complications of PCI (side branch occlusion, unsealed dissection, embolisation).

Practice points

' In people with ACS, initiate cardiac monitoring immediately, with ST-segment ischaemia monitoring where available. Continue uninterrupted for a minimum of 24 hours. ' People with ACS post-PCI should be monitored, with STsegment ischaemia monitoring where available, continuously and uninterrupted for 24 hours. ' Reevaluate the need for continuous ECG monitoring every 24 hours. ' Educate staff regarding proper skin preparation, assessment of skin turgor and ECG electrode replacement every 24 hours, as this reduces inappropriate alarms [ 492 , 493 ]. ' Further guidance regarding cardiac monitoring can be found on the Agency for Clinical Innovation website ( aci. health.nsw.gov.au/cardiac ) [ 491 ].

4. Recovery and Secondary Prevention

Following ACS, participation in exercise-based cardiac rehabilitation and person-centred, secondary prevention programs (collectively termed cardiovascular risk management programs) is essential to help reduce future vascular events and improve quality of life and prognosis [ 494 ]. Participation in these programs facilitates earlier return to usual activities including work.

Engagement with these programs bene ﬁ ts all people with ACS, including women, older adults, regional and remote residents, First Nations peoples, and people from culturally and linguistically diverse backgrounds [ 67 , 494 ].

Risk management programs complement the care provided by a person ’ s general practitioner and other allied healthcare professionals in the community. These programs address the following:

' Supporting people to manage their recovery post-ACS and adopt healthy behaviours (e.g. quitting smoking and/or drug and alcohol use, being physically active, eating healthily and maintaining good mental health). ' Intensive clinical risk factor education and modi ﬁ cation (e.g. managing blood pressure, lowering blood lipids, optimising diabetes management). ' Filling prescriptions, reaf ﬁ rming adherence to guidelineindicated medicines and facilitating review for actual and potential medicine-related harm, when suspected. ' Educating people on appropriate management of new or ongoing symptoms post-discharge, including use of antianginal medicines and when to seek urgent medical attention. ' Taking actions to protect against in ﬂ uenza and other pathogens, exposure to climate extremes, severe air pollution and cardiac toxins where applicable. ' Empowering people and their carers/support people towards greater self-care and management of their underlying cardiac status and comorbidities.

A system-generated referral to a ﬂ exible, tailored risk management program should be made prior to the person ’ s discharge from hospital.

Prior to discharge, it is also crucial to ensure the person has a scheduled post-discharge review appointment with a member of their treating team (e.g. cardiologist, specialist cardiac nurse). This is important to address any immediate issues including medicines adherence, wound management and emotional and mental wellbeing.

4.1. Person-Centred Non-Pharmacological Secondary Prevention

Recommendations

|Recommendation| Strength of recommendation | Certainty of evidence | |---|---|---| | For all people with ACS, |Strong| Moderate | | refer to a multi-disciplinary||| |exercise-based cardiac||| |rehabilitation program||| | prior to discharge.||| |||| | For all people with ACS,||Consensus| | provide advice on lifestyle*||| |changes such as healthy||| |eating, regular physical||| |activity, not smoking,||| |limiting alcohol intake, and||| | caring for mental health.||| | For all people with ACS|Strong| Moderate| |who smoke, advise to stop||| | and refer for behavioural||| |intervention (such as||| | cognitive behaviour||| |therapy or cessation||| |counselling program),||| |combined with||| |pharmacotherapy where||| |appropriate (nicotine||| |replacement therapies,||| |varenicline and bupropion||| |individually or in||| |combination).||| | For all people with ACS,|Consensus|| |implement strategies to||| | optimise adherence to||| | preventive medicines.|||

\*Use of the word lifestyle here refers to a collective group of modi ﬁ able risk factors. The authors wish to acknowledge that these risk factors are not solely dependent on individual choice, and instead re ﬂ ect the cultural, social and environmental factors that in ﬂ uence behaviour. This term does not in any way attribute blame to individuals.

Evidence supporting the recommendations

Cardiac rehabilitation is a structured, multidisciplinary program that delivers tailored interventions to people post-ACS (and those with other cardiac conditions). Key components of

these comprehensive programs include exercise training and physical activity, cardiovascular risk factor management, nutritional advice, medicines education and mental health support. Various cardiac rehabilitation delivery models are available, including in-person or via telehealth, group or individual, and home-, hospital- or community-based.

A contemporary systematic review of 85 trials randomised 23,430 people (predominantly post-MI and postrevascularisation) to either exercise-based cardiac rehabilitation or usual care with a median follow-up of 12 months (range 6 months to 19 years). Results showed meaningful reductions in MI and all-cause hospital admissions (RR 0.82, $95\%$ CI 0.70 – 0.96 and RR 0.77, $95\%$ CI 0.67 – 0.89, respectively) [ 494 ]. Although risk reductions in cardiovascular mortality were reported (RR 0.74, $95\%$ CI 0.64 – 0.86), the certainty of evidence was downgraded due to imprecision. There was no signi ﬁ cant effect on all-cause mortality (RR 0.96, $95\%$ CI 0.89 – 1.04) and cardiovascular hospitalisation (RR 0.85, $95\%$ CI 0.67 – 1.08). There was limited evidence of improved health-related quality of life and cost-effectiveness. The overall effects were independent of cardiac rehabilitation delivery models, exercise doses, duration of follow up, or risk of bias. A ﬂ exible, cardiovascular risk management program is a reasonable alternative [ 495 ].

Smoking cessation is strongly associated with decreased risk of subsequent non-fatal and fatal MI [ 496 , 497 ]. Smoking is prevalent among people hospitalised with ACS. An observational study in 9,375 people with ACS with a mean follow-up of 3.9 years found an $80\%$ higher risk of death among those who continued to smoke compared with lifelong non-smokers and people who quit smoking [ 498 ].

Suboptimal adherence to prescribed medicines following ACS is associated with an increased risk of poor outcomes including cardiac-related rehospitalisation and mortality [ 499 ]. An observational analysis of 3,441 people with ACS found that $45\%$ were not taking prescribed lipid-lowering medicines at 12 months post-event [ 500 ]. Similarly, a large prospective audit of 2,299 people with ACS evaluated the proportion that received optimal secondary prevention care [ 501 ]. Only $65\%$ were discharged with appropriate medicines including antiplatelets, lipid-lowering medicines, beta blockers and angiotensin converting enzyme (ACE) inhibitors. Commencing people with ACS on guideline-recommended therapies while in hospital is strongly predictive of adherence at 6 months [ 502 ]. Implementing strategies to ensure prescription of preventative medicines at discharge, in addition to providing person-centred medicines education, are critical to improving adherence.

Practice points

Cardiac rehabilitation and secondary prevention programs ' Cardiac rehabilitation and secondary prevention programs should offer evidence-based aerobic and resistance training in accordance with the current Cardiac Society of Australia and New Zealand (CSANZ) Position Statement

[ 503 ]. Where an exercise-based cardiac rehabilitation program is not available, refer to a ﬂ exible, cardiovascular risk management program. ' Evidence-based cardiac rehabilitation programs should be tailored, where possible, to meet the unique needs of groups with low attendance rates, including women and people from culturally and linguistically diverse communities [ 504 , 505 ]. B For First Nations peoples, enable access to cardiac rehabilitation programs facilitated by Aboriginal and Torres Strait Islander health practitioners wherever possible. B For people whose ﬁ rst language is not English, enable access to bilingual educators wherever possible. ' For people with ACS living in regional and remote communities, cardiac rehabilitation via telehealth is an acceptable alternative to in-person programs [ 506 ]. The Cardiac Services Directory ( cardiacserviceslist. heartfoundation.org.au ) on the Heart Foundation website lists cardiac rehabilitation programs available throughout Australia, including those delivered via telehealth. ' Embed system-generated referral to a cardiac rehabilitation/risk management program based on a person ’ s preference, values and the available resources [ 507 – 512 ]. ' Consider use of digital health interventions in the delivery of cardiovascular risk management programs post-ACS such as reminders, text messaging, mobile health (mHealth) apps, telehealth consultations, wearable devices and electronic decision support tools [ 510 , 513 , 514 ]. ' Exercise-induced cardiac events are negligible in comparison to the risk associated with being habitually sedentary [ 515 ].

Lifestyle management

' Provide relevant disease and lifestyle education; the latter covering healthy eating, regular physical activity, not smoking, limiting alcohol intake and caring for mental health. Refer to the Heart Foundation website for guidance and resources on these topics. ' Screen people with ACS for depression and other mental health conditions using validated tools and refer for appropriate mental health support as required. People with ACS commonly experience feelings of low mood, sadness, guilt, worry and anger [ 516 – 519 ].

Medicines adherence

' Provide effective medicines education during hospital admission and at time of discharge. This should include discussion of: B what each medicine is for, the strength and dose, and when and how to take it B the importance of continuing to take medicines as prescribed, and not stopping or changing the dose unless advised by their GP B what to do if the person misses a dose B potential side effects and what to do if the person believes they are experiencing a side effect. ' Implement practical strategies to promote adherence, such as daily alerts/reminders, combining medicines where

possible ( ﬁ xed combination medicines) and pharmacyprovided medicine packs.

' Consider post-discharge comprehensive medicine review, particularly in those with signi ﬁ cant medicine changes, polypharmacy and/or multimorbidity, those on high-risk medicines such as anticoagulants, and those at risk of medicine non-adherence [ 520 ].

Follow-up care

' Provide a verbal and written discharge summary that includes: B the diagnosis and treatment, including investigation ﬁ ndings B scheduled follow-up appointments (post-discharge review with the treating team, general practitioner, cardiac rehabilitation) B medicines commenced, altered or ceased while in hospital, and the importance of taking medicines as prescribed B healthy lifestyle changes and practical strategies to implement these B a chest pain/angina management plan. ' Ensure chest pain/angina management plans include guidance management of new or ongoing symptoms postdischarge, including use of anti-anginal medicines, and when and how to seek urgent medical attention (i.e. calling Triple Zero (000) for an ambulance rather than driving to hospital). ' Two-way communication between the discharging hospital and the person ’ s general practitioner is critical to support the ongoing care of people with ACS. Similarly, encourage people with ACS to establish/maintain regular contact with their general practitioner for ongoing follow up. ' Initiate a general practitioner management plan or team care arrangement to assist in the management of comorbidities. This is particularly important for older adults with geriatric syndromes including frailty, impaired cognitive function, and polypharmacy [ 507 – 512 ].

4.2. Vaccination Against In ﬂ uenza and Other Respiratory Pathogens

Recommendations

|Recommendation|Strength of|Certainty of| |---|---|---| ||recommendation|evidence| | In people with ACS,|Consensus|| |vaccinations for||| |influenza and other||| |respiratory pathogens||| | are recommended.|||

Evidence supporting the recommendations

In people with ACS, an international contemporary trial which randomised 2,571 people with STEMI or NSTEMI to in ﬂ uenza vaccine or placebo found that in ﬂ uenza vaccine reduced the primary composite outcome of all-cause death, MI, or stent thrombosis (HR 0.72, $95\%$ CI 0.52 – 0.99) at one year follow up [ 521 ]. The ﬁ ndings are consistent with those from a meta-analysis of randomised trials and observational studies comprising almost 240,000 people with cardiovascular disease and a median follow-up of 19.5 months. In ﬂ uenza vaccination was associated with reduced risk of all-cause and cardiovascular mortality but not MI when compared with the control group [ 522 ]. The Australian immunisation handbook outlines recommendations for people with CAD and other chronic cardiac conditions regarding respiratory syncytial virus (RSV), in ﬂ uenza, pneumococcal disease and COVID-19 vaccination [ 523 ].

Practice points

' People with CAD should receive in ﬂ uenza and pneumococcal vaccinations as per recommended schedules [ 523 ]. The in ﬂ uenza vaccine can be safely administered within 72 hours of hospitalisation for AMI, including for an invasive coronary procedure [ 521 ]. ' People aged ${\ge}60$ years with CAD receive RSV vaccination due to their increased risk of severe RSV disease [ 523 ]. ' People with chronic cardiac conditions, including coronary heart disease, are at increased risk of severe COVID-19 and may bene ﬁ t from additional doses of COVID-19 vaccine.

4.3. Post-ACS Pharmacotherapy

4.3.1. Antiplatelet therapy Recommendations

|Recommendation| Strength of recommendation || |---|---|---| |Recommendation| Strength of recommendation | Certainty OF evidence | |||| | In people discharged|Strong|High| |following an ACS who are at||| |high ischaemic and/or low||| |bleeding risk, prescribe DAPT||| |with aspirin and a P2Y12||| |inhibitor for 6-12 months.||| |||| | In people discharged|Strong|High| |following an ACS who are at||| |low ischaemic and/or high||| |bleeding risk, cease DAPT at||| |1-3 months post-ACS and||| | continue single antiplatelet||| ||||

|(continued).||| |---|---|---| |Recommendation|Strength of| Certainty OF | ||recommendation|| ||| evidence | | In people discharged|Strong|Moderate| |following an ACS who have||| |completed a course of DAPT||| |(i.e. 1-12 months), prescribe||| | long-term P2Y12 inhibitor over||| |||| | In people discharged|Weak| Moderate| |following an ACS who remain||| |at high ischaemic and low||| |bleeding risk, consider long-||| |term DAPT (>12 months).||| | In people discharged|Strong|| |following an ACS with an||High| |indication for long-term OAC||| |therapy, continue OAC and||| | DAPT (preferentially aspirin||| |and clopidogrel) for 1-4||| |weeks, then cease aspirin.||| |||| | In people discharged| Strong|Moderate| |following an ACS with an||| |indication for long-term OAC||| | therapy, cease antiplatelet therapy at 6-12 months and ||| |||| |continue anticoagulation||| |alone.|||

Evidence supporting the recommendations

The landmark $\mathrm{P}2\mathrm{Y}_{12}$ inhibitor trials in people with ACS undergoing PCI reported primary outcomes following 9 – 12 months of DAPT which became the standard duration of therapy [ 387 , 388 ]. However, these trials were designed in the era of early generation drug eluting stents when late stent thrombosis was more common than is seen in current practice.

More recent studies regard long duration therapy as being up to 6 months, particularly among people that have been stented. This is based on the observation that the incidence of ischaemic events plateaus by this time while cumulative bleeding risk continues to rise [ 524 ].

Studies on DAPT are dominated by people undergoing PCI, with those managed by CABG or medical treatment alone con ﬁ ned to subgroup analyses. Therefore, the applicability of these recommendations to non-PCI groups is less clear.

Short term vs standard duration of DAPT in people with ACS Improved ischaemic outcomes attributable to developments in stent technologies and secondary prevention strategies have prompted several studies exploring outcomes following shorter duration DAPT, driven principally by the desire to reduce bleeding risk. These trials have compared short-term

(1 – 3 months) DAPT against standard term (6 – 12 months) DAPT after which aspirin or the $\mathrm{P}2\mathrm{Y}_{12}$ inhibitor is ceased, leaving the other as SAPT.

A meta-analysis of RCTs in people with ACS undergoing PCI $\scriptstyle(\mathfrak{n}=25,907)$ ) compared 1 – 3 months with 6 – 12 months of DAPT followed by SAPT. The study found a signi ﬁ cant reduction in bleeding events in the 1 – 3 month treatment group (HR 0.47, $95\%$ CI 0.47 – 0.62) with no signi ﬁ cant differences in MACE [ 408 ]. This study also reported a trend towards increased MACE with short-term DAPT in people with STEMI, left main or left anterior descending artery disease (i.e. high ischaemic risk) [ 408 ].

In short duration DAPT studies, the antiplatelet selected for continuation as SAPT has most commonly been a $\mathrm{P}2\mathrm{Y}_{12}$ inhibitor (clopidogrel or ticagrelor). A network meta-analysis of people with ACS (24,838 patient-years of follow-up) and stable counterparts (85,221 patient-years) undergoing stenting showed continuation of a $\mathrm{P}2\mathrm{Y}_{12}$ inhibitor rather than aspirin appears to provide the best trade-off to reduce risk of both major bleeding and MI [ 525 , 526 ].

People at high bleeding risk

Several scores are available to predict HBR in people receiving DAPT following PCI. The PRECISE-DAPT score was developed to provide a standardised tool for predicting mid-term (1-year) bleeding events during DAPT in an allcomers PCI population, and shows similar discriminative capacity for bleeding when compared with the older CRUSADE and ACUITY scores [ 527 , 528 ]. The ARC-HBR is an alternative pragmatic approach recommended in European guidelines [ 142 ].

A meta-analysis in people at HBR $\scriptstyle(\mathfrak{n}=9,006)$ ) found that 1 – 3 months DAPT signi ﬁ cantly reduced major or clinically relevant non-major bleeding (RR 0.76, $95\%$ CI 0.61 – 0.94) with no difference in MACE [ 529 ]. There was no difference in outcomes when aspirin or $\mathrm{P}2\mathrm{Y}_{12}$ was used for continuing SAPT.

Another meta-analysis in people at HBR ( $\scriptstyle(\mathfrak{n}=16,848,$ including people receiving OAC therapy), compared shortterm DAPT ( $'{\le}3$ months) followed by aspirin or $\mathrm{P}2\mathrm{Y}_{12}$ inhibitor SAPT against standard DAPT (6 – 12 months) after PCI [ 530 ]. Compared with standard DAPT, major bleeding was lower with short-term DAPT (OR 0.68, $95\%$ CI 0.51 – 0.89). Incidence of MI, all-cause death, cardiovascular death, stroke, or stent thrombosis was not statistically different. Similar ﬁ ndings have been reported in people with HBR undergoing complex PCI [ 343 ].

Long-term SAPT

A network meta-analysis of people after PCI ( $\scriptstyle(\mathfrak{n}=73,126;$ consistent ﬁ ndings in ACS sensitivity analysis) found that compared with DAPT (of 1 – 18 months duration), $\mathrm{P}2\mathrm{Y}_{12}$ inhibitor and aspirin monotherapies reduced bleeding. However, the risk of MI was similar with a $\mathrm{P}2\mathrm{Y}_{12}$ inhibitor and increased with aspirin monotherapy [ 531 ].

A meta-analysis of people with established vascular disease (n=61,623, $30\%$ with ACS) found that $\mathrm{P}2\mathrm{Y}_{12}$ inhibitor monotherapy reduced the risk of MACE (composite of stroke, MI, or death in the majority of studies) by $11\%$

![Commence all people with AcS on DAPT regardless of revascularisation strategy Aspirin+potentP2Y12inhibitor (ticagrelororprasugrel\*) Lowischaemicand/or High ischaemic and/or Persistinghighischaemic high bleeding risk lowbleeding risk and low bleeding risk 1-3 months OR Durationof de-escalation 6-12months >12 months DAPT after 1month Long termsingleantiplatelettherapy Ticagrelor#orclopidogrelpreferredoveraspirin ](https://venus-llm-1258344701.cos-internal.ap-guangzhou.tencentcos.cn/userUpload/is-62e36cd9/2025-04-10/9cd22017-d2ed-4cce-9a50-de84d6cbf04c/9cd22017-d2ed-4cce-9a50-de84d6cbf04c.jpg?q-sign-algorithm=sha1&q-ak=AKID61g5D5fy1TjiRv84nEOHtFJ8gyzjCPL0&q-sign-time=1744240805%3B1744244405&q-key-time=1744240805%3B1744244405&q-header-list=host&q-url-param-list=&q-signature=a583e0e8b534d8a66abf28953da450fb3b32fd84) Figure 15 Decision tree for dual antiplatelet therapy (DAPT) duration following an ACS. \*Prasugrel is not currently available in Australia. U Refers to the de-escalation of DAPT to aspirin and a less potent $\mathrm{P}2\mathrm{Y}_{12}$ inhibitor (clopidogrel). # Current Pharmaceutical Bene ﬁ ts Scheme criteria preclude the prescription of ticagrelor as single therapy. Abbreviations: ACS, acute coronary syndromes; CABG, coronary artery bypass grafting; PCI, percutaneous coronary intervention.

compared with aspirin monotherapy (RR 0.89, $95\%$ CI 0.84 – 0.95) [ 532 ]. This ﬁ nding was consistent irrespective of the $\mathrm{P}2\mathrm{Y}_{12}$ inhibitor used (clopidogrel or ticagrelor, $\mathsf{p{=}0.83})$ . There was also no signi ﬁ cant difference in the risk of major bleeding with $\mathrm{P}2\mathrm{Y}_{12}$ inhibitor monotherapy compared with aspirin (RR 0.94, $95\%$ CI 0.72 – 1.22).

These ﬁ ndings align with those from a meta-analysis (seven RCTs) in 24,325 people with CAD, including 12,178 people receiving $\mathrm{P}2\mathrm{Y}_{12}$ inhibitor monotherapy (clopidogrel 7,545 $[62\%]$ ; ticagrelor 4,633 $[38\%]$ ) and 12,147 people assigned to receive aspirin [ 533 ].

To note, ticagrelor is not currently subsidised on the Pharmaceutical Bene ﬁ ts Scheme (PBS) as monotherapy. Current PBS criteria state ticagrelor must be prescribed in combination with aspirin.

Prolonged $_{\cdot>T2}$ months) duration of DAPT

A study of 21,162 people with previous MI (1 – 3 years earlier), found that DAPT with ticagrelor and aspirin was associated with a reduction in the composite outcome of cardiovascular death, MI or stroke compared with aspirin alone (HR 0.85, $95\%$ CI 0.75 – 0.96), which was balanced by an increase in major bleeding (HR 2.69, $95\%$ CI 1.96 – 3.7) [ 534 ].

A meta-analysis $\scriptstyle(\mathfrak{n}=25,985.$ , $42.4\%$ ACS) comparing prolonged DAPT $(>\!12$ months) with standard DAPT (6 – 12 months) following PCI found that prolonged DAPT reduced the risk of MI and stent thrombosis, but increased the risk of bleeding, compared with standard DAPT. There was no

difference in the risk of all-cause death or cardiovascular death [ 535 ]. People with a prior MI, with ACS at presentation, without diabetes, or younger than 75 years may derive the most ischaemic bene ﬁ t from extended DAPT.

A pooled post-hoc analysis of eight RCTs $\scriptstyle(\mathfrak{n}=14,963)$ ) of people treated with PCI, strati ﬁ ed by PCI complexity and bleeding risk, found that long-term DAPT reduced ischaemic events in non-HBR people in both complex (absolute risk

|Table 11| Determinants of recurrent ischaemic risk|| |---|---|---| |following an ACS [343,408].||| || High ischaemic risk | Persisting high ischaemic risk | |Aged |||

\*Complex PCI: ${>}2$ stents/lesions/vessels treated, bifurcation stenting, ${\tt>}60~\mathrm{mm}$ of stent, chronic total occlusion. Abbreviations: ACS, acute coronary syndromes; DAPT, dual antiplatelet therapy; PCI, percutaneous coronary intervention; STEMI, ST-segment elevation myocardial infarction.

Table 12 The Academic Research Consortium (ARC) high bleeding risk criteria. Adapted with permission from Urban et al. [ 342 ].

High bleeding risk ARC score (one major and two minor criteria)

Major criteria

Minor criteria

' Anticipated long term OAC use ' Age ${>}75$ years ' Severe CKD (eGFR , 30 mL/min) ' Moderate CKD ' Hb ${<}11~\mathrm{g/DL} $ (eGFR 30 – 59 mL/ ' Spontaneous bleeding requiring min) hospitalisation ' Hb 11 – 12.9 g/dL for or transfusion in the past men and 11 – 11.9 six months or at g/dL for women any time if recurrent ' Spontaneous ' Baseline platelet count ${<}100{\times}10^{9}/\mathrm{L} $ bleeding requiring ' Chronic bleeding diathesis hospitalisation ' Liver cirrhosis with portal or transfusion within hypertension 12 months not ' Active malignancy within meeting major 12 months criteria ' Previous spontaneous ICH ' Long term NSAID (at any time) or steroid use ' Traumatic ICH within 12 months ' Prior ischaemic ' Brain arteriovenous malformation stroke not meeting ' Moderate or severe ischaemic stroke major criterion within 12 months ' Recent major surgery or major trauma within 30 days before PCI

Abbreviations: ARC, Academic Research Consortium; CKD, chronic kidney disease; eGFR, estimated glomerular ﬁ ltration rate; Hb, haemoglobin; ICH, intracranial haemorrhage; NSAID, nonsteroidal antiin ﬂ ammatory drug; OAC, oral anticoagulant; PCI, percutaneous coronary intervention.

difference: $-3.86\%$ ; $95\%$ CI 2 7.71 – 0.06) and noncomplex PCI (absolute risk difference: $-1.14\%$ ; $95\%$ CI 2 2.26 – 2 0.02). There was no bene ﬁ t of prolonged DAPT seen in people with HBR. Results in people with ACS at presentation were consistent with the whole cohort [ 343 ]. Refer to Figure 15 and Table 11 and Table 12 for guidance on DAPT duration following an ACS.

People with atrial ﬁ brillation requiring long-term anticoagulation A meta-analysis of the four DOAC-based RCTs comparing dual antithrombotic therapy with triple antithrombotic therapy in people with atrial ﬁ brillation undergoing PCI (n=10,234, . 50% ACS) found signi ﬁ cantly less bleeding with dual therapy (clopidogrel $^+$ DOAC) (RR 0.63, $95\%$ CI 0.50 – 0.79). While there was no difference in the composite of ischaemic events for dual therapy, there was a signi ﬁ cant increase in stent thrombosis (RR 1.60, $95\%$ CI 1.02 – 2.52) [ 536 ]. In

each of these studies, aspirin was administered periprocedurally and was ceased from one day to one week following PCI in the dual antithrombotic arms.

A subsequent network meta-analysis of ﬁ ve RCTs $\scriptstyle(\mathfrak{n}=11,542)$ ) comparing different double and triple antithrombotic regimens found that non-vitamin K OAC plus $\mathrm{P}2\mathrm{Y}_{12}$ inhibitor without aspirin had the best safety pro ﬁ le, when compared with treatments that included aspirin (as a component of triple therapy) or vitamin K antagonists [ 537 ].

Additional secondary and pooled analyses of these studies have found that stent thrombosis was highest in the ﬁ rst 30 days after randomisation, with higher rates in the nonaspirin group [ 538 ]. This suggested the potential for increased thrombotic complications among people receiving dual therapy (i.e. no aspirin) within the ﬁ rst month [ 536 , 539 ]. It may therefore be reasonable to continue aspirin for up to one month following PCI in people who are not at HBR, although this recommendation is based on consensus opinion and has not been speci ﬁ cally addressed in any of the randomised trials [ 436 ].

A trial evaluating longer term antithrombotic therapy in people requiring anticoagulation found that ceasing SAPT at 6 months and continuing with a DOAC for more than one year following stenting had no effect on ischaemic or bleeding events in people with HBR [ 540 ]. Another trial of DOAC-containing regimens showed that concomitant treatment with aspirin compared with DOAC monotherapy for more than one year following stenting was associated with increased mortality with event rates of $4\%$ and $6\%$ per patient-year, respectively (HR 0.72, $95\%$ CI 0.55 – 0.95) [ 541 ]. Antiplatelet therapy should be ceased and the DOAC continued at 12 months in people following an ACS with an indication for long-term OAC.

Refer to Figure 16 for guidance on recommended antiplatelet treatment strategies for people with ACS requiring long-term DOAC for atrial ﬁ brillation.

Practice points

Short term vs standard duration of DAPT in people with ACS

' In older people (e.g. ${\geq}70$ years)with ACS, particularlyif HBR, consider clopidogrel as the $\mathrm{P}2\mathrm{Y}_{12}$ receptor inhibitor [ 28 ].

People at high bleeding risk

' A mobile phone-based application has been developed to assist with decision-making for people at HBR (see www. cerc-europe.org/arc-hbr-high-bleeding-risk-evaluator/ ). This is based on an algorithm that predicts risk of major ischaemic and bleeding events [ 542 ]. ' In people receiving DAPT with high risk of gastrointestinal bleeding, a proton pump inhibitor is recommended.

People requiring long-term anticoagulation

' In people with ACS undergoing PCI with other conditions that require long-term anticoagulation (e.g. mechanical heart valve), lack of evidence prevents recommendations being made.

' The recommendations in this section can be applied to people with ACS and MI undergoing medical management [ 407 ]. ' In people who have undergone PCI and are at HBR, deescalating therapy to anticoagulation alone after 6 months may be reasonable [ 436 ]. ' In people receiving triple therapy, a proton pump inhibitor is recommended.

4.3.2. Lipid-modifying therapy Recommendations

|Recommendation| Strength of recommendation | Certainty OF evidence | |---|---|---| | In people with ACS, prior to hospital discharge, initiate and |Strong|High| |||| |continue indefinitely, the||| |highest tolerated dose of||| |HMG-CoA reductase||| | inhibitors (statins), unless||| |contraindicated or completely||| |statin intolerant.||| | In people with ACS with|Weak|LOW| |initial or partial intolerance to||| |statin, consider using a||| | different statin, dose or dosing||| | frequency to achieve person-||| | specific therapeutic objectives.||| | In people with ACS, an initial | Consensus|| |target low density lipoprotein||| |cholesterol (LDL-C) level of||| ||||

Evidence supporting the recommendations

In a meta-analysis of statin therapy versus controls in a subset of people with pre-existing vascular disease $\scriptstyle(\mathfrak{n}=64,443;$ ; $45\%$ ACS) the composite endpoint of MI, stroke, coronary revascularisation or vascular death was reduced by $20\%$ for

every 1.0 mmol/L reduction in LDL-C [ 543 ]. Similar bene ﬁ ts were found in a meta-analysis of high versus lower dose statin therapy [ 544 ]. These randomised trials of statin therapy before or after PCI in people with ACS $\mathrm{(n{=}6,743)}$ ) found high-dose versus no- or low-dose statins reduced the combined outcomes of death, recurrent MI and stroke by $28\%$ (OR 0.82, $95\%$ CI 0.70 – 0.95) beyond 30 days. This aligned with the lower risk of MI and MACE at 30 days. The latter bene ﬁ t occurred within the ﬁ rst 6 months after ACS [ 543 ].

A meta-analysis of placebo-controlled RCTs $\scriptstyle(\mathfrak{n}=123,940)$ , $16.4\%$ ACS) found almost half $(48\%)$ reported at least one episode of muscle pain or weakness during a median of 4.3 years corresponding to a $3\%$ relative increase in those taking statins compared with placebo (RR 1.03, $95\%$ CI 1.01 – 1.06) [ 543 ]. Up to $70\%$ of people reporting statin intolerance may tolerate reduced dose regimens or substitution of a hydrophilic statin [ 545 ].

The IMPROVE-IT randomised trial in people with ACS $\scriptstyle(\mathfrak{n}=18,144)$ found a modest reduction in study-speci ﬁ c MACE in the statin-ezetimibe group versus statin monotherapy (HR 0.936, $95\%$ CI 0.89 – 0.99) [ 546 ].

Monoclonal antibodies to PCSK9, known as PCSK9 inhibitors, are very effective at signi ﬁ cantly lowering LDL-C in people already receiving intensive lipid-lowering therapy. Examples of PCSK9 inhibitors include alirocumab, evolocumab and inclisiran. In a randomised trial of 18,924 people with a recent ACS on maximally tolerated statins and an LDL-C of at least $1.8\,\mathrm{{mm}/\mathrm{{L},}}$ , the PCSK9 inhibitor alirocumab reduced the composite cardiovascular endpoint over a median follow up of 2.8 years (HR 0.85 95% CI 0.78 – 0.93) compared with placebo. There was also a lower risk of all-cause mortality favouring active treatment over placebo [ 547 ].

Practice points

' Initiate or continue high-potency statin therapy (e.g. atorvastatin or rosuvastatin) as early as possible during the ACS admission, irrespective of baseline LDL-C level [ 544 ]. ' For people on lipid-lowering therapy prior to index ACS admission, consider intensifying existing lipid-lowering therapy. ' Re-assess total cholesterol and LDL-C levels approximately four to six weeks after initiating or intensifying treatment. Adjust statin therapy or add non-statin therapy according to whether levels are at target values. Note that additional nonstatin therapies are frequently required to achieve target LDL-C levels and to prevent recurrent coronary events. ' In people with ACS (men ${<}55$ years and women ${<}60$ years), the Dutch Lipid Clinic Network score can guide the need for diagnostic genetic testing. If genetic predisposition is con ﬁ rmed, consider cascade testing, genetic counselling, and initiating statins in family members [ 548 ]. ' In people with ACS with triglyceride levels of 1.5 – 5.6 mmol/L and LDL-C 1.0 – 2.6 mmol/L despite statin therapy, consider adding icosapent ethyl [ 549 ]. Note that the current PBS eligibility criteria for icosapent ethyl is a triglyceride level of 1.7 mmol/L. # DAPT: aspirin plus clopidogrel preferred. \*SAPT: clopidogrel preferred. Note: People receiving triple therapy should be given a proton pump inhibitor. Abbreviations: ACS, acute coronary syndromes; DAPT, dual antiplatelet therapy; DOAC, direct oral anticoagulant; SAPT, single antiplatelet therapy.

![TimefromAcs Default antiplatelet Antiplateletstrategyforpeople strategy athighischaemicrisk DOAC+DAPT# DOAC+DAPT# Upto1week Up to 1 month DOAC+SAPT\* 6months DOAC+SAPT\* DOAC+ DOACalone SAPT\* 12months Beyond12months DOACalone ](https://venus-trag-1258344701.cos-internal.ap-guangzhou.tencentcos.cn/userUpload/is-62e36cd9/2025-04-10/945af753-3d63-47eb-bd86-fea6e7a788c9/945af753-3d63-47eb-bd86-fea6e7a788c9.jpg?q-sign-algorithm=sha1&q-ak=AKID61g5D5fy1TjiRv84nEOHtFJ8gyzjCPL0&q-sign-time=1744240805%3B1744244405&q-key-time=1744240805%3B1744244405&q-header-list=host&q-url-param-list=&q-signature=60f77d459f40b9e1e00b28b0e4dc22c35339bcf0) Figure 16 Recommended antiplatelet treatment strategies for people with ACS requiring long-term DOAC for atrial ﬁ brillation.

Women

' In women at risk of a major vascular event, commence statin therapy [ 550 ]. ' Note that women are less likely than men to be prescribed statin therapy post-ACS [ 551 ].

Older adults

' In older adults with evidence of occlusive vascular disease (such as prior MI), consider statin therapy to reduce the risk of major vascular events [ 552 ].

4.3.3. Beta blocker therapy Recommendations

|Recommendation|| |---|---| || Strength of Certainty recommendationnof Evidence | | In people with ACS and LV|| |impairment, beta blockers are|| | recommended.|| | ||

|(continued).||| |---|---|---| |Recommendation|Strength of| Certainty of Evidence | ||recommendation|| | In people with ACS and|Weak|Moderate| | preserved LV systolic||| |function who have||| |undergone coronary||| | revascularisation and are||| | receiving optimal medical||| |therapy, consider||| |withholding beta blockers.|||

Evidence supporting the recommendations

In a meta-analysis of RCTs ( $\mathbf{\langlen=}102\mathbf{,}003$ people post-MI), beta blockers lowered all-cause mortality in the prereperfusion era (incidence rate ratio [IRR] 0.86, $95\%$ CI 0.79 – 0.94), but not in the reperfusion era (IRR 0.98, $95\%$ CI 0.92 – 1.05), (P interaction =0.02) [ 553 ]. However, signi ﬁ cant reductions in recurrent MI occurred in both the pre-reperfusion

and reperfusion eras, respectively (IRR 0.78, $95\% $ CI 0.78 – 0.98 and IRR 0.72, $95\%$ CI 0.62 – 0.83). The reduced effect on mortality in the reperfusion era likely re ﬂ ects a reduction in the frequency and severity of LV dysfunction, as the bene ﬁ ts of beta blockers in people with LV dysfunction are well established [ 554 , 555 ].

Findings from the REDUCE-AMI study are consistent with the hypothesis that beta blockers are of limited value in the absence of LV dysfunction. This randomised registry-based trial enrolling 5,020 people with AMI and preserved ejection fraction, undergoing early angiography, showed that long-term use of beta blockers did not reduce the composite endpoint of all-cause death and MI at 3.5 years of follow-up [ 556 ].

Practice points

' In people with MI and risk factors for cardiogenic shock, exercise caution when initiating beta blockers as these people may be at increased risk of early mortality [ 557 ]. ' IV beta blockade in STEMI prior to PCI has not been shown to reduce death or MI at one year [ 558 , 559 ]. ' In people with con ﬁ rmed LV dysfunction, consider using a beta blocker of proven bene ﬁ t in heart failure with reduced ejection fraction (speci ﬁ cally bisoprolol, carvedilol, metoprolol [controlled or extended release], or nebivolol). See the Guidelines for the prevention, detection, and management of heart failure in Australia for further details including other recommended therapies [ 490 ]. ' In people with preserved ejection fraction, no bene ﬁ t in continuing beta blockers beyond 12 months has been seen, but more research on this is being undertaken [ 560 – 563 ]. ' In asymptomatic people discharged following an episode of UA (i.e. without MI) and with normal LVEF, there is paucity of evidence for protection against MACE from beta blocker therapy in the absence of other indications.

4.3.4. Renin-angiotensin antagonist therapies Recommendations

|Recommendation|Strength of|| |---|---|---| ||recommendation| Certainty of Evidence | | In people with ACS and|Strong|High| |heart failure symptoms,||| |LVEF |||

|(continued).||| |---|---|---| |Recommendation| Strength of| Certainty of Evidence | ||recommendation|| | In people with ACS and|Strong|High| |LVEF ≤40% and heart||| |failure with or without||| |diabetes, initiate and||| |continue||| |mineralocorticoid||| |receptor antagonists.||| | In people with ACS, use|Strong|High| | of an angiotensin||High| |receptor-neprilysin||| |inhibitor is not||| |recommended.|||

Evidence supporting the recommendations

A meta-analysis of randomised trials in AMI $\scriptstyle(\mathfrak{n}=98,496)$ , indicated use of ACE inhibitors results in a $7\%$ decrease in mortality at 30 days, with the greatest bene ﬁ t in people with heart failure or anterior MI [ 564 ].

The evidence for long-term bene ﬁ t comes from a metaanalysis of randomised trials of people with stable vascular disease ( $\mathsf{(n{=}29{,}805{,}$ ; ${>}50\%$ with prior MI) where long-term use of ACE inhibitors signi ﬁ cantly reduced cardiovascular mortality, non-fatal MI and stroke in the context of long-term secondary prevention (OR 0.82, $95\%$ CI 0.76 – 0.88) [ 565 ]. However, a more recent meta-analysis of ACE inhibitor or angiotensin receptor blocker treatment in people with coronary disease $\scriptstyle(\mathfrak{n}=61,961$ ) found that this bene ﬁ t was not seen in people receiving active antihypertensive therapy, or those with low anticipated event rates [ 566 ]. The recommendations, then, are for the longterm use of these medicines in people with anticipated high event rates, particularly those with conditions shown to bene ﬁ t from ACE inhibition such as diabetes, hypertension, or chronic kidney disease.

Angiotensin receptor blockers have been shown to have a comparable effect to ACE inhibitors in people post-MI with reduced LVEF [ 567 ].

In an RCT of people with recent MI and LV dysfunction and symptoms of either heart failure or a diagnosis of diabetes $\mathbf{(n{=}6,}632)$ ), the mineralocorticoid receptor antagonist, eplerenone, in combination with standard therapy within 3 – 14 days of an AMI reduced mortality and cardiovascular hospitalisations (RR 0.87, $95\%$ CI 0.79 – 0.95) [ 568 ].

In a randomised trial $\mathbf{(n{=}5,}661$ , post-MI with LVEF ${\leq}40\%$ or transient pulmonary congestion), people received either an angiotensin receptor-neprilysin inhibitor or ACE inhibitor before hospital discharge. There was no difference in cardiovascular death or incident heart failure at 22 months [ 569 ]. Therefore, angiotensin receptor-neprilysin inhibitors are not recommended in this context.

Practice points

' In people with ACS and LVEF ${\geq}40\%$ or without clinical heart failure, consider use of ACE inhibitors (or angiotensin receptor blockers if ACE inhibitors not tolerated) to improve survival [ 566 ]. ' For people with ACS and concurrent hypertension, ACE inhibitors and angiotensin receptor blockers are indicated as ﬁ rst-line agents for hypertension management. Current blood pressure management and targets are provided in the Heart Foundation ’ s Guideline for the diagnosis and management of hypertension in adults [ 570 ]. ' In people with ACS and heart failure, ongoing management should align with the Guidelines for the prevention, detection, and management of heart failure in Australia , with consideration of referral to specialised heart failure services to optimise care and improve outcomes [ 490 ].

4.3.5. Colchicine therapy Recommendation

|Recommendation|Strength of| Certainty of evidence | |---|---|---| |||| | In people with ACS,|Weak|Moderate| | consider initiating||| |colchicine (0.5 mg daily)||| | and continuing long-term||| |unless contraindicated or||| |colchicine intolerant.|||

Evidence supporting the recommendation

Residual in ﬂ ammation in the coronary vasculature after ACS may contribute to subsequent reinfarction. Antiin ﬂ ammatory medicines such as colchicine have the potential to directly address such an in ﬂ ammatory environment, thereby minimising the risk of recurrent MACE.

A systematic review and meta-analysis $\mathrm{(n{=}7,}207)$ of people with ACS, with ${<}1$ month to 22.6 months follow-up, found that colchicine resulted in a lower risk of coronary revascularisation (RR 0.46, $95\%$ CI 0.29 – 0.73) and stroke (RR 0.39, $95\%$ CI 0.18 – 0.81) [ 571 ]. There was no signi ﬁ cant difference in all-cause mortality (RR 1.25, $95\%$ CI 0.70 – 2.24), cardiovascular mortality, or recurrent MI. Colchicine increased the risk of gastrointestinal adverse reactions (RR 1.89, $95\%$ CI 1.25 – 2.84).

A randomised trial of people with MI $\mathrm{(n{=}7,062)}$ ) found no bene ﬁ t of colchicine on the composite cardiovascular endpoint of death from cardiovascular causes, recurrent MI, stroke, or unplanned ischemia-driven coronary revascularisation at a median follow up of 3 years (HR 0.99, $95\%$ CI 0.85 – 1.16, $\mathrm{{P}{=}0.93.}$ ). Further meta-analyses integrating this trial with prior studies are needed to con ﬁ rm the limited role of colchicine in the management of people post-ACS.

Acknowledgements

The guideline authors would like to gratefully thank the following people for their valuable contribution:

' Members of the Consumer Advisory Panel for ensuring the content aligns with the values and preferences of people living with cardiovascular disease in Australia. $\bigcirc$ Darren Hicks (Chair) B David Follent B Sarah Hatzivlastou B Sharon Kort B Michael McGowan B Jarrod McMaugh B Léa Zeestraten ' Professor Derek P. Chew (MBBS, MPH, FRACP, PhD) for his contribution and involvement as the guideline ’ s independent reviewer. ' Jacinta Hegarty, Acting First Nations Heart Health Lead, National Heart Foundation of Australia, for her contribution to section 1.4 Collaborative Approaches to Care for First Nations Peoples .

Funding

The guideline was jointly funded by the National Heart Foundation of Australia and the Cardiac Society of Australia and New Zealand (CSANZ). Funding was also received from trusts managed by Perpetual for the guideline development in 2020 and 2021.

Endorsements

Organisations that have endorsed this guideline can be found on the National Heart Foundation of Australia website at: https://www.heartfoundation.org.au/for-professionals/ acs-guideline .

Declaration of Competing Interests

For a full list of disclosures/con ﬂ icts of interest, refer to Supplementary Material A2 .

Appendices

Supplementary Materials associated with this article can be found at https://doi.org/10.1016/j.hlc.2025.02.102

Appendices

Appendix A. Abbreviations and Acronyms

|ACE|angiotensin converting enzyme| |---|---| |ACOMI| acute coronary occlusion myocardial infarction| |ACS|acute coronary syndromes| |ACTION|Acute coronary treatment and intervention outcomes network| |ACUITY|Acute catheterization and urgent intervention triage strategy| |AMI| acute myocardial infarction| |ARC-HBR| Academic Research Consortium high bleeding risk | |CABG|coronary artery bypass grafting| |CAD| coronary artery disease| |CDP| clinical decision pathway| |CH|confidence interval| |CK-MB|creatine kinase MB-isoenzyme| |COPD| chronic obstructive pulmonary disease| |CRUSADE| Can rapid risk stratification of unstable angina patients suppress adverse outcomes with early implementation of the ACC/AHA guidelines | ||| |CSANZ|Cardiac Society of Australia and New Zealand| |CTCA| computed tomography coronary angiography| |cHn| cardiac troponin| | cTnI cTnT | cardiac troponin I| || cardiac troponin T| |DAPT| dual antiplatelet therapy| |DOAC| direct oral anticoagulants| |ECG| electrocardiogram| |ED|emergency department| | EDACS eGFR |Emergency department assessment of chest pain score| ||estimated glomerular filtration rate| |ESG| Expert steering group| |FFR|fractional flow reserve| |GPI|glycoprotein IIb/IIla inhibitor| |GRACE| Global Registry of Acute Coronary Events | |GRADE| Grading of recommendations, assessment, development and evaluation| |HBR|high bleeding risk| | HEART High-STEACS |History, electrocardiogram, age, risk factors, troponin| || High sensitivity troponin in the evaluation of patients with acute coronary syndrome| |IHIR|hazard ratio| |hs-cTn|high-sensitivity cardiac troponin| |IR| international normalised ratio| |IRA| infarct-related artery| |IRR|incidence rate ratio| || intravenous| |IVI| intravascular imaging| |IIVUS| intravascular ultrasound| |K8|kilogram| | LBBB LDL-C |left bundle branch block| ||low density lipoprotein cholesterol| |LMWH| low molecular weight heparin| || left ventricular| |LVEF|left ventricular ejection fraction| |LVH| left ventricular hypertrophy| |MACE| major adverse cardiovascular events| |m8| milligram|

Appendix A. Continued

|II| myocardial infarction| |---|---| |MINOCA|myocardial infarction with non-obstructive coronary arteries| |mL/min|millilitres per minute| |mm|millimetre| |mmol/L|millimoles per litre| |RI|magnetic resonance imaging| |MVD|multivessel disease| |ng/L|nanograms per litre| |NHMRC| National Health and Medical Research Council| |NSAIDS| non-steroidal anti-inflammatory medicines| |NSTEACS| non-ST-segment elevation acute coronary syndromes| |NSTEMI| non-ST-segment elevation myocardial infarction| |OAC| oral anticoagulant| |OR|odds ratio| ||probability| |PBS| Pharmaceutical Benefits Scheme| |PCI| percutaneous coronary intervention| |PET|positron emission tomography| |PICOTS| patient/population, intervention, comparison, outcome, time, setting| |POC| point-of-care| |RCT|randomised controlled trial| |IRIR|risk ratio| |RSW| respiratory syncytial virus| |SaO2|arterial oxygen saturation| |SAPT| single antiplatelet therapy| |SCAD|spontaneous coronary artery dissection| |SPECT|stress/rest single-photon emission computed tomography| |SPO2| oxygen saturation| |STE| ST-segment elevation| |STEACS|ST-segment elevation acute coronary syndromes| |STEMI| ST-segment elevation myocardial infarction| |TIMI|Thrombolysis in myocardial infarction| |tPA|tissue plasminogen activator| |UA|unstable angina| |UDMI|Universal definition of myocardial infarction| |UFHI|unfractionated heparin| |UK|United Kingdom| |VA-ECMO|venoarterial extracorporeal membrane oxygenation| |u8| microgram| |Hg/L|microgram per litre|

Appendix B Terminology and De ﬁ nitions

||| |---|---| |Chest pain - cardiac| Chest pain due to an underlying cardiac aetiology. Includes classic chest discomfort based on | || quality, location, radiation, and provoking and relieving factors that make it more likely to be of cardiac ischaemic origin. | ||| |Chest pain - non-cardiac|Chest pain symptoms likely due to a non-cardiac cause.| |Chest pain - possible cardiac|Chest pain symptoms that suggest a cardiac origin.| |Coronary artery disease (CAD)| CAD refers to the narrowing and/or blockage of the coronary arteries due to accumulation of plaque (atherosclerosis). | | Coronary heart disease| Coronary heart disease refers to heart muscle damage that is caused by CAD, where there is reduced blood flow through the coronary arteries. Coronary heart disease is the major underlying cause of acute coronary syndromes. | ||| | Coronary microvascular dysfunction| Epicardial or microvascular endothelial or non-endothelial dysfunction that limits| |Heart failure| myocardial perfusion, most often detected as reduced coronary flow reserve. Heart failure is a complex clinical syndrome resulting from any structural or functional impairment of ventricular filling or ejection of blood. The main manifestations of heart failure | |Heart failure| Heart failure is a complex clinical syndrome resulting from any structural or functional impairment of ventricular filling or ejection of blood. The main manifestations of heart failure are dyspnoea and fatigue (which may limit exercise tolerance) and fluid retention. These may | |Heart failure|| |Heart failure|lead to pulmonary or splanchnic congestion and/or peripheral oedema.| || There is no single diagnostic test for heart failure; it is largely a clinical diagnosis based on a careful history and physical examination including 12-lead ECG, chest X-ray, transthoracic | ||| ||echocardiography and laboratory blood testing. When the diagnosis is unclear following| || initial clinical assessment and an echocardiogram cannot be arranged in a timely fashion, measurement of plasma natriuretic peptide levels is recommended. MI is the irreversible necrosis of heart muscle. A common cause of infarction is deprivation in myocardial oxygen supply due to interruption of blood flow in at least one coronary artery | |Myocardial infarction (MI)|| |Myocardial infarction (MI)|| |Myocardial infarction (MI)|caused by plaque rupture, erosion, fissure, or coronary dissection.| |Myocardial infarction (MI)| bradyarrhythmias, anaemia, hypoxaemia, coronary artery spasm, spontaneous coronary artery dissection (SCAD), coronary embolism, and coronary microvascular dysfunction. Type 3 MI is MI resulting in death when biomarkers are not available. Types 4 and 5 MI relate to percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) respectively | |Myocardial infarction (MI)|| |Myocardial infarction (MI)| and accurate detection of MI is important for initiating and maintaining appropriate therapy. In clinical trials, lack of a uniform MI definition can result in low concurrence between theIn clinical trials, lack of a uniform MI definition can result in low concurrence between the initial clinical and later adjudicated assessments of Ml, which will affect accuracy of primaryinitial clinical and later adjudicated assessments of Ml, which will affect accuracy of primary end points and trial outcomes. Thus, uniform definitions are needed to ensure accurate | |Myocardial infarction (MI)| end points and trial outcomes. Thus, uniform definitions are needed to ensure accurate reporting of MI events across clinical trials and registries. | |MI - Type 1 as per Fourth UDMI|| |MI - Type 1 as per Fourth UDMI| Type 1 MI is characterised by atherosclerotic plaque rupture, ulceration, fissure, or erosion with resulting intraluminal thrombus in one or more coronary arteries leading to decreased myocardial blood flow and/or distal embolisation and subsequent myocardial necrosis. The person may have underlying CAD but non-obstructive coronary atherosclerosis or there may | |MI - Type 1 as per Fourth UDMI|| |MI - Type 2 as per Fourth UDMI| person may have underlying CAD but non-obstructive coronary atherosclerosis or there may be no angiographic evidence of CAD. Type 2 MI is myocardial necrosis associated with an imbalance between myocardial oxygen | || Type 2 MI is myocardial necrosis associated with an imbalance between myocardial oxygen supply and demand, and may be associated with hypotension, hypertension, tachy/ bradyarrhythmias, anaemia, hypoxaemia, coronary artery spasm, spontaneous coronary artery dissection (SCAD), coronary embolism, and coronary microvascular dysfunction. Type 3 MI is MI resulting in death when biomarkers are not available. | | MI - Type 3 as per Fourth UDMI MI - Type 4 and 5 as per Fourth UDMI || | MI - Type 3 as per Fourth UDMI MI - Type 4 and 5 as per Fourth UDMI ||

Appendix B. (continued).

|Term|Definition|| |---|---|---| | Myocardial infarction with non- obstructive coronary arteries (MINOCA) ||| | Myocardial infarction with non- obstructive coronary arteries (MINOCA) || The diagnosis of MINOCA is made in people with acute myocardial infarction (AMI) that fulfills all following criteria: | | Myocardial infarction with non- obstructive coronary arteries (MINOCA) ||| | Myocardial infarction with non- obstructive coronary arteries (MINOCA) | fulfills all following criteria: 1. AMI (modified from the Fourth universal definition of myocardial infarction criteria [15]): Detection of a rise or fall of cardiac troponin (cTn) with at least one value above the 99th percentile upper reference limit and corroborative clinical evidence of infarction based on || | Myocardial infarction with non- obstructive coronary arteries (MINOCA) ||| | Myocardial infarction with non- obstructive coronary arteries (MINOCA) |● symptoms of myocardial ischaemia|| | Myocardial infarction with non- obstructive coronary arteries (MINOCA) |● new ischaemic electrocardiographic changes|| | Myocardial infarction with non- obstructive coronary arteries (MINOCA) |· development of pathological Q waves|| | Myocardial infarction with non- obstructive coronary arteries (MINOCA) | · imaging evidence of new loss of viable myocardium or new regional wall motion ab- normality in a pattern consistent with an ischaemic cause ● identification of a coronary thrombus by angiography or autopsy. || |||| ||| 2. Non-obstructive coronary arteries on angiography, defined as the absence of obstructive disease on angiography (i.e. no coronary artery stenosis ≥ 50%) in any major epicardial | |||| || absence of obstructive disease). This includes people with normal coronary arteries (no angiographic stenosis), mild luminal irregularities (angiographic stenosis ||

Appendix B. (continued).

|Term|Definition| |---|---| |Older adults| Adults older than 75 years old. | | Pericarditis| Pericarditis is inflammation of the pericardial layers characterised by chest pain,| ||electrocardiographic changes, and often pericardial effusion. It is often caused by an| || infectious or non-infectious process but can also be idiopathic.| || Pericarditis usually presents with sharp pleuritic chest pain, which may be improved by| ||sitting up or leaning forward, although in many instances such findings are not present. A| ||pericardial friction rub may be audible. Widespread STE with PR depression is the| | Pulmonary embolism| electrocardiographic hallmark, although changes are non-specific and may be transient. Intravascular migration of a venous thrombus to the pulmonary arterial circulation. It isIntravascular migration of a venous thrombus to the pulmonary arterial circulation. It is diagnosed by a positive pulmonary angiogram, an unequivocally positive helical CT scan, a high-probability ventilation-perfusion scan, or autopsy. | ||| |Regional and remote|Based on the Australian Bureau of Statistics Australian Statistical Geography Standard| || (ASGS) Edition 3 Remoteness Structure that categorises areas based on relative access to services. Categories are 'major cities', 'inner regional', 'outer regional', 'remote' and 'very remote'. | | Spontaneous coronary artery dissection (SCAD) || | Spontaneous coronary artery dissection (SCAD) | Epicardial coronary artery dissection that is not associated with atherosclerosis or trauma and is not iatrogenic. Predominant mechanism of myocardial injury occurring due to SCAD is coronary artery obstruction caused by an intramural hematoma or intimal disruption | ||rather than atherosclerotic plaque rupture or intraluminal thrombus.| |ST-segment elevation myocardial|STEMI is characterised by the presence of both criteria:| |infarction (STEMI)| 1. Electrocardiographic evidence of STEMI: new or presumed new ST-segment elevation at the J-point in two contiguous leads with the cut-off point: ≥ 1 mm in all leads other than leads V2-V3 where the following cut off points apply: ≥2 mm in men ≥40 years; ≥2-5 | || the J-point in two contiguous leads with the cut-off point: ≥ 1 mm in all leads other than leads V2-V3 where the following cut off points apply: ≥2 mm in men ≥40 years; ≥2-5 mm in men |

References

[1] Aroney CN, Aylward P, Chew DP, Huang N, Kelly AM, White H, et al. 2007 addendum to the National Heart Foundation of Australia/Cardiac Society of Australia and New Zealand Guidelines for the management of acute coronary syndromes 2006. Med J Aust. 2008;188:302 – 3 . [2] Chew DP, Aroney CN, Aylward PE, Kelly AM, White HD, Tideman PA, et al. 2011 Addendum to the National Heart Foundation of Australia/ Cardiac Society of Australia and New Zealand Guidelines for the management of acute coronary syndromes (ACS) 2006. Heart Lung Circ. 2011;20:487 – 502 . [3] Acute Coronary Syndrome Guidelines Working Group. Guidelines for the management of acute coronary syndromes 2006. Med J Aust. 2006;184:S1 – 32 . [4] Schünemann H, Bro zek J, Guyatt G, Oxman A. GRADE Handbook: Introduction to GRADE Handbook. Available at: gdt.gradepro.org/ app/handbook/handbook.html ; 2013. [5] National Health and Medical Research Council. 2016 NHMRC Standards for Guidelines. Available at www.nhmrc.gov.au/guidelines forguidelines/standards . [6] Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck-Ytter Y, AlonsoCoello P, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ. 2008;336:924 – 6 . [7] Australian Commission on Safety and Quality in Health Care. Acute Coronary Syndromes Clinical Care Standard. Available at: www. safetyandquality.gov.au/sites/default/ ﬁ les/2019-12/acute_coronary_ syndromes_ccs_-_december_2019.pdf ; 2019. [8] Australian Institute of Health and Welfare. Heart, Stroke and vascular disease: Australian facts. Available at www.aihw.gov.au/reports/ heart-stroke-vascular-diseases/hsvd-facts . [accessed 16.8.24]. [9] The National Heart Foundation of Australia. Acute coronary syndromes (ACS) clinical guidelines. Available at: www.heartfoundation.org.au/ for-professionals/fp-acs-guidelines . [accessed 9.1.25]. [10] Stehli J, Martin C, Brennan A, Dinh DT, Lefkovits J, Zaman S. Sex differences persist in time to presentation, revascularization, and mortality in myocardial infarction treated with percutaneous coronary intervention. J Am Heart Assoc. 2019;8:e012161 . [11] Khan E, Brieger D, Amerena J, Atherton JJ, Chew DP, Farshid A, et al. Differences in management and outcomes for men and women with STelevation myocardial infarction. Med J Aust. 2018;209:118 – 23 . [12] Stehli J, Dinh D, Dagan M, Duffy SJ, Brennan A, Smith K, et al. Sex differences in prehospital delays in patients with ST-segment – elevation myocardial infarction undergoing percutaneous coronary intervention. J Am Heart Assoc. 2021;10:e019938 . [13] Australian Institute of Health and Welfare. Estimating the incidence of stroke and acute coronary syndrome using the National Integrated Health Services Information Analysis Asset. Available at: www.aihw. gov.au/reports/heart-stroke-vascular-diseases/incidence-of-stroke-acutecoronary-syndrome/contents/technical-report . [accessed 20.12.24]. [14] Australian Institute of Health and Welfare. Better Cardiac Care measures for Aboriginal and Torres Strait Islander people. Available at www.aihw.gov.au/reports/indigenous-australians/better-cardiac-caremeasures-for-indigenous-people/summary . [accessed 14.8.24]. [15] Thygesen K, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA, et al. Fourth universal de ﬁ nition of myocardial infarction (2018). Circulation. 2018;138(20):e618 – 51 . [16] Gulati M, Levy PD, Mukherjee D, Amsterdam E, Bhatt DL, Birtcher KK, 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. J Am Coll Cardiol. 2021;70(22):e187 – 285 . [17] Wong GC, Welsford M, Ainsworth C, Abuzeid W, Fordyce CB, Greene J, et al. 2019 Canadian Cardiovascular Society/Canadian Association of Interventional Cardiology Guidelines on the acute management of STelevation myocardial infarction: focused update on regionalization and reperfusion. Can J Cardiol. 2019;35(2):107 – 32 . [18] de Lemos JA, Newby LK, Mills NL. A proposal for modest revision of the de ﬁ nition of type 1 and type 2 myocardial infarction. Circulation. 2019;140(22):1773 – 5 . [19] Chapman AR, Shah ASV, Lee KK, Anand A, Francis O, Adamson P, et al. Long-term outcomes in patients with type 2 myocardial infarction and myocardial injury. Circulation. 2018;137(12):1236 – 45 . [20] Nestelberger T, Boeddinghaus J, Badertscher P, Twerenbold R, Wildi K, Breitenbücher D, et al. Effect of de ﬁ nition on incidence and prognosis of type 2 myocardial infarction. J Am Coll Cardiol. 2017;70(13):1558 – 68 . et al. Discrimination of patients with type 2 myocardial infarction. Eur Heart J. 2017;38(47):3514 – 20 . [22] Tzimas G, Antiochos P, Monney P, Eeckhout E, Meier D, Fournier S, et al. Atypical electrocardiographic presentations in need of primary percutaneous coronary intervention. Am J Cardiol. 2019;124(8):1305 – 14 . [23] Shah ASV, Anand A, Strachan FE, Ferry AV, Lee KK, Chapman AR, et al. High-sensitivity troponin in the evaluation of patients with suspected acute coronary syndrome: a stepped-wedge, cluster-randomised controlled trial. Lancet. 2018;392(10151):919 – 28 . [24] Reichlin T, Twerenbold R, Maushart C, Reiter M, Moehring B, Schaub N, et al. Risk strati ﬁ cation in patients with unstable angina using absolute serial changes of 3 high-sensitive troponin assays. Am Heart J. 2013;165(3):371 – 8 . [25] Reichlin T, Twerenbold R, Reiter M, Steuer S, Bassetti S, Balmelli C, et al. Introduction of high-sensitivity troponin assays: impact on myocardial infarction incidence and prognosis. Am J Med. 2012;125(12):1205 – 13 . [26] Nedkoff L, Goldacre R, Greenland M, Goldacre MJ, Lopez D, Hall N, et al. Comparative trends in coronary heart disease subgroup hospitalisation rates in England and Australia. Heart. 2019;105(17):1343 . [27] Tamis-Holland JE, Jneid H, Reynolds HR, Agewall S, Brilakis ES, Brown TM, et al. Contemporary diagnosis and management of patients with myocardial infarction in the absence of obstructive coronary artery disease: a scienti ﬁ c statement from the American Heart Association. Circulation. 2019;139(18):e891 – 908 . [28] Byrne RA, Rossello X, Coughlan JJ, Barbato E, Berry C, Chieffo A, et al. 2023 ESC Guidelines for the management of acute coronary syndromes. Eur Heart J. 2023;44(38):3720 – 826 . [29] Australian Commission on Safety and Quality in Health Care. Partnering with Consumers Standard. Available at www.safetyandquality. gov.au/standards/nsqhs-standards/partnering-consumers-standard . [accessed 14.8.24]. [30] Elwyn G, Frosch D, Thomson R, Joseph-Williams N, Lloyd A, Kinnersley P, et al. Shared decision making: a model for clinical practice. J Gen Intern Med. 2012;27(10):1361 – 7 . [31] Lin GA, Fagerlin A. Shared decision making: state of the science. Circ Cardiovasc Qual Outcomes. 2014;7(2):328 – 34 . [32] Dennison Himmelfarb CR, Koirala B, Coke LA. Shared decision making: partnering with patients to improve cardiovascular care and outcomes. J Cardiovasc Nurs. 2018;33(4):301 – 3 . [33] Klein LW, Anderson HV, Cigarroa J. Shared decision-making in cardiovascular practice. Cardiol Rev. 2023;31(1):52 – 6 . [34] Mitropoulou P, Grüner-Hegge N, Reinhold J, Papadopoulou C. Shared decision making in cardiology: a systematic review and meta-analysis. Heart. 2022;109(1):34 – 9 . [35] Turkson-Ocran RN, Ogunwole SM, Hines AL, Peterson PN. Shared decision making in cardiovascular patient care to address cardiovascular disease disparities. J Am Heart Assoc. 2021;10(20):e018183 . [36] Lauck S, Lewis K. Shared decision-making in cardiac care: can we close the gap between good intentions and improved outcomes? Heart. 2022;109(1):4 – 5 . [37] Australian Institute of Health and Welfare. Cultural competency in the delivery of health services for Indigenous people. Available at www. aihw.gov.au/reports/indigenous-australians/cultural-competency-inthe-delivery-of-health-serv/summary . [accessed 11.11.24]. [38] Chew DP, Scott IA, Cullen L, French JK, Briffa TG, Tideman PA, et al. National Heart Foundation of Australia and Cardiac Society of Australia and New Zealand: Australian clinical guidelines for the management of acute coronary syndromes 2016. Med J Aust. 2016;205(3):128 – 33 . [39] Cullen L, Greenslade J, Merollini K, Graves N, Hammett CJK, Hawkins T, et al. Cost and outcomes of assessing patients with chest pain in an Australian emergency department. Med J Aust. 2015;202(8):427 – 32 . [40] Chapman AR, Lee KK, McAllister DA, Cullen L, Greenslade JH, Parsonage W, et al. Association of high-sensitivity cardiac troponin I concentration with cardiac outcomes in patients with suspected acute coronary syndrome. JAMA. 2017;318(19):1913 – 24 . [41] Sörensen NA, Neumann JT, Ojeda F, Schäfer S, Magnussen C, Keller T, et al. Relations of sex to diagnosis and outcomes in acute coronary syndrome. J Am Heart Assoc. 2018;7(6):e007297 . [42] Twerenbold R, Neumann JT, Sörensen NA, Ojeda F, Karakas M, Boeddinghaus J, et al. Prospective validation of the 0/1-h algorithm for early diagnosis of myocardial infarction. J Am Coll Cardiol. 2018; 72(6):620 – 32 . [43] Fanaroff AC, Rymer JA, Goldstein SA, Simel DL, Newby LK. Does this patient with chest pain have acute coronary syndrome? The rational clinical examination systematic review. JAMA. 2015;314(18):1955 – 65 . [44] Hsia RY, Hale Z, Tabas JA. A national study of the prevalence of lifethreatening diagnoses in patients with chest pain. JAMA Intern Med. 2016;176(7):1029 – 32 . [45] van der Meer MG, Backus BE, van der Graaf Y, Cramer MJ, Appelman Y, Doevendans PA, et al. The diagnostic value of clinical symptoms in women and men presenting with chest pain at the emergency department, a prospective cohort study. PLoS One. 2015;10(1): e0116431 . [46] Rof ﬁ M, Patrono C, Collet JP, Mueller C, Valgimigli M, Andreotti F, et al. 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC). Eur Heart J. 2016;37(3):267 – 315 . [47] Rubini Gimenez M, Reiter M, Twerenbold R, Reichlin T, Wildi K, Haaf P, et al. Sex-speci ﬁ c chest pain characteristics in the early diagnosis of acute myocardial infarction. JAMA Intern Med. 2014;174(2):241 – 9 . [48] National Institute for Health and Care Excellence. Guideline scope: acute coronary syndromes (unstable angina, NSTEMI, STEMI): management and secondary prevention (update). 2020 [49] Department of Health and Aged Care. Australian Guideline for assessing and managing cardiovascular disease risk 2023. Available at www.cvdcheck.org.au/ . [accessed 20.12.24]. [50] Adlam D, Alfonso F, Maas A, Vrints C, Writing C. European Society of Cardiology, acute cardiovascular care association, SCAD study group: a position paper on spontaneous coronary artery dissection. Eur Heart J. 2018;39(36):3353 – 68 . [51] Dang QM, Psaltis PJ, Burgess S, Chandrasekhar J, Mukherjee S, Kritharides L, et al. The Australian-New Zealand Spontaneous Coronary Artery Dissection Cohort study: predictors of major adverse cardiovascular events and recurrence. Eur Heart J. 2025; in press . [52] Raphael CE, Heit JA, Reeder GS, Bois MC, Maleszewski JJ, Tilbury RT, et al. Coronary embolus: an underappreciated cause of acute coronary syndromes. JACC: Cardiovasc Imaging. 2018;11:172 – 80 . [53] Shimokawa H, Suda A, Takahashi J, Berry C, Camici PG, Crea F, et al. Clinical characteristics and prognosis of patients with microvascular angina: an international and prospective cohort study by the Coronary Vasomotor Disorders International Study (COVADIS) Group. Eur Heart J. 2021;42:4592 – 600 . [54] Talarico GP, Crosta ML, Giannico MB, Summaria F, Calò L, Patrizi R. Cocaine and coronary artery diseases: a systematic review of the literature. J Cardiovasc Med. 2017;18:291 – 4 . [55] Kevil CG, Goeders NE, Woolard MD, Bhuiyan MS, Dominic P, Kolluru GK, et al. Methamphetamine use and cardiovascular disease. Arterioscler Thromb Vasc Biol. 2019;39:1739 – 46 . [56] Crea F, Camici PG, Bairey Merz CN. Coronary microvascular dysfunction: an update. Eur Heart J. 2014;35:1101 – 11 . [57] Lichtman JH, Leifheit EC, Safdar B, Bao H, Krumholz HM, Lorenze NP, et al. Sex differences in the presentation and perception of symptoms among young patients With myocardial infarction. Circulation. 2018;137:781 – 90 . [58] Khan NA, Daskalopoulou SS, Karp I, Eisenberg MJ, Pelletier R, Tsadok MA, et al. Sex differences in prodromal symptoms in acute coronary syndrome in patients aged 55 years or younger. Heart. 2017;103:863 . [59] Ferry AV, Anand A, Strachan FE, Mooney L, Stewart SD, Marshall L, et al. Presenting symptoms in men and women diagnosed with myocardial infarction using sex-speci ﬁ c criteria. J Am Heart Assoc. 2019;8:e012307 . [60] Pelletier R, Khan NA, Cox J, Daskalopoulou SS, Eisenberg MJ, Bacon SL, et al. Sex versus gender-related characteristics: which predicts outcome after acute coronary syndrome in the young? J Am Coll Cardiol. 2016;67:127 – 35 . [61] Hemal K, Pagidipati NJ, Coles A, Dolor RJ, Mark DB, Pellikka PA, et al. Sex differences in demographics, risk factors, presentation, and noninvasive testing in stable outpatients with suspected coronary artery disease: insights from the PROMISE Trial. JACC: Cardiovasc Imaging. 2016;9:337 – 46 . [62] Chiaramonte GR, Friend R. Medical students ’ and residents ’ gender bias in the diagnosis, treatment, and interpretation of coronary heart disease symptoms. Healthy Psychol. 2006;25:255 – 66 . [63] Jokhadar M, Wenger NK. Review of the treatment of acute coronary syndrome in elderly patients. Clin Interv Aging. 2009;4:435 – 44 . [64] Gupta R, Munoz R. Evaluation and management of chest pain in the elderly. Emerg Med Clin North Am. 2016;34:523 – 42 . [65] Lowenstern A, Alexander KP, Hill CL, Alhanti B, Pellikka PA, Nanna MG, et al. Age-related differences in the noninvasive evaluation for possible coronary artery disease: insights from the Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE) Trial. JAMA Cardiol. 2020;5:193 – 201 . [66] Nanna MG, Hajduk AM, Krumholz HM, Murphy TE, Dreyer RP, Alexander KP, et al. Sex-based differences in presentation, treatment, and complications among older adults hospitalized for acute myocardial infarction: the SILVER-AMI Study, 12. Circ Cardiovasc Qual Outcomes; 2019, e005691 . [67] Damluji AA, Forman DE, Wang TY, Chikwe J, Kunadian V, Rich MW, et al. Management of acute coronary syndrome in the older adult population: a scienti ﬁ c statement from the American Heart Association. Circulation. 2023;147:e32 – 62 . [68] Ilton MK, Walsh WF, Brown ADH, Tideman PA, Zeitz CJ, Wilson J. A framework for overcoming disparities in management of acute coronary syndromes in the Australian Aboriginal and Torres Strait Islander population. A consensus statement from the National Heart Foundation of Australia. Med J Aust. 2014;200:639 – 43 . [69] Stephensen L, Greenslade J, Starmer K, Starmer G, Stone R, Bonnin R, et al. Clinical characteristics of Aboriginal and Torres Strait Islander emergency department patients with suspected acute coronary syndrome. Emerg Med Australas. 2023;35:442 – 9 . [70] Diercks DB, Peacock WF, Hiestand BC, Chen AY, Pollack CV Jr, Kirk JD, et al. Frequency and consequences of recording an electrocardiogram ${>}10$ minutes after arrival in an emergency room in non-ST-segment elevation acute coronary syndromes (from the CRUSADE Initiative). Am J Cardiol. 2006;97:437 – 42 . [71] Dee F, Savage L, Leitch JW, Collins N, Loten C, Fletcher P, et al. Management of acute coronary syndromes in patients in rural Australia: The MORACS randomized clinical trial. JAMA Cardiol. 2022;7:690 – 8 . [72] Scirica BM, Morrow DA, Budaj A, Dalby AJ, Mohanavelu S, Qin J, et al. Ischemia detected on continuous electrocardiography after acute coronary syndrome: observations from the MERLIN-TIMI 36 (Metabolic Ef ﬁ ciency With Ranolazine for Less Ischemia in Non-ST-Elevation Acute Coronary Syndrome-Thrombolysis In Myocardial Infarction 36) trial. J Am Coll Cardiol. 2009;53:1411 – 21 . [73] Ryan TJ, Anderson JL, Antman EM, Braniff BA, Brooks NH, Califf RM, et al. ACC/AHA guidelines for the management of patients with acute myocardial infarction: executive summary. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Acute Myocardial Infarction). Circulation. 1996;94:2341 – 50 . [74] Barbagelata A, Ware DL. Denying reperfusion or falsely declaring emergency: the dilemma posed by ST-segment elevation. J Electrocardiol. 2006;39:S73 – 4 . [75] Pendell Meyers H, Bracey A, Lee D, Lichtenheld A, Li WJ, Singer DD, et al. Accuracy of OMI ECG ﬁ ndings versus STEMI criteria for diagnosis of acute coronary occlusion myocardial infarction. Int J Cardiol Heart Vasc. 2021;33:100767 . [76] Miranda DF, Lobo AS, Walsh B, Sandoval Y, Smith SW. New insights into the use of the 12-lead electrocardiogram for diagnosing acute myocardial infarction in the emergency department. Can J Cardiol. 2018;34:132 – 45 . [77] Warren J, Mehran R, Yu J, Xu K, Bertrand ME, Cox DA, et al. Incidence and impact of totally occluded culprit coronary arteries in patients presenting with non-ST-segment elevation myocardial infarction. Am J Cardiol. 2015;115:428 – 33 . [78] Durant E, Singh A. Acute ﬁ rst diagonal artery occlusion: a characteristic pattern of ST elevation in noncontiguous leads. Am J Med. 2015;33:1326 . [79] Littmann L. South African ﬂ ag sign: a teaching tool for easier ECG recognition of high lateral infarct. Am J Med. 2016;34:107 – 9 . [80] Schmitt C, Lehmann G, Schmieder S, Karch M, Neumann FJ, Schömig A. Diagnosis of acute myocardial infarction in angiographically documented occluded infarct vessel Chest, 120; 2001. p. 1540 – 6 . [81] Vives-Borrás M, Moustafa A-H, Álvarez-García J, Ferrero-Gregori A, Balcells J, García-Picart J, et al. Clinical and prognostic value of the electrocardiogram in patients with acute occlusion of the left circum ﬂ ex coronary artery. Am J Cardiol. 2017;120:1487 – 94 . [82] de Winter RJ, Verouden NJ, Wellens HJ, Wilde AA. A new ECG sign of proximal LAD occlusion. N Engl J Med. 2008;359:2071 – 3 . [83] Inohara T, Kohsaka S, Fukuda K, Menon V. The challenges in the management of right ventricular infarction. Eur Heart J Acute Cardiovasc Care. 2013;2:226 – 34 . [84] Haji SA, Movahed A. Right ventricular infarction – diagnosis and treatment. Clin Cardiol. 2000;23:473 – 82 . [85] de Winter RW, Adams R, Verouden NJ, de Winter RJ. Precordial junctional ST-segment depression with tall symmetric T-waves signifying proximal LAD occlusion, case reports of STEMI equivalence. J Electrocardiol. 2016;49:76 – 80 . [86] Smith SW, Dodd KW, Henry TD, Dvorak DM, Pearce LA. Diagnosis of ST-elevation myocardial infarction in the presence of left bundle branch block with the ST-elevation to S-wave ratio in a modi ﬁ ed Sgarbossa rule. Ann Emerg Med. 2012;60:766 – 76 . [87] Cai Q, Mehta N, Sgarbossa EB, Pinski SL, Wagner GS, Califf RM, et al. The left bundle-branch block puzzle in the 2013 ST-elevation myocardial infarction guideline: from falsely declaring emergency to denying reperfusion in a high-risk population. Are the Sgarbossa Criteria ready for prime time? Am Heart J. 2013;166:409 – 13 . [88] Sgarbossa EB, Pinski SL, Barbagelata A, Underwood DA, Gates KB, Topol EJ, et al. Electrocardiographic diagnosis of evolving acute myocardial infarction in the presence of left bundle-branch block. GUSTO-1 (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries) Investigators. N Engl J Med. 1996;334:481 – 7 . [89] de Zwaan C, Bär FW, Wellens HJ. Characteristic electrocardiographic pattern indicating a critical stenosis high in left anterior descending coronary artery in patients admitted because of impending myocardial infarction. Am Heart J. 1982;103:730 – 6 . [90] Knotts RJ, Wilson JM, Kim E, Huang HD, Birnbaum Y. Diffuse ST depression with ST elevation in aVR: Is this pattern speci ﬁ c for global ischemia due to left main coronary artery disease? J Electrocardiol. 2013;46:240 – 8 . [91] Wong CK, Gao W, Stewart RA, Benatar J, French JK, Aylward PE, et al. aVR ST elevation: an important but neglected sign in ST elevation acute myocardial infarction. Eur Heart J. 2010;31:1845 – 53 . [92] Koechlin L, Strebel I, Zimmermann T, Nestelberger T, Walter J, LopezAyala P, et al. Hyperacute T wave in the early diagnosis of acute myocardial infarction. Ann Emerg Med. 2023;82:194 – 202 . [93] Smith SW, Meyers HP. Hyperacute T-waves can be a useful sign of occlusion myocardial infarction if appropriately de ﬁ ned. Ann Emerg Med. 2023;82:203 – 6 . [94] Kaul P, Fu Y, Chang WC, Harrington RA, Wagner GS, Goodman SG, et al. Prognostic value of ST segment depression in acute coronary syndromes: insights from PARAGON-A applied to GUSTO-IIb. PARAGON-A and GUSTO IIb Investigators. Platelet IIb/IIIa Antagonism for the Reduction of Acute Global Organization Network. J Am Coll Cardiol. 2001;38:64 – 71 . [95] Savonitto S, Cohen MG, Politi A, Hudson MP, Kong DF, Huang Y, et al. Extent of ST-segment depression and cardiac events in non-STsegment elevation acute coronary syndromes. Eur Heart J. 2005;26:2106 – 13 . [96] Gifft K, Ghadban R, Assefa N, Luebbering Z, Allaham H, Enezate T. The accuracy of distribution of non-ST elevation electrocardiographic changes in localising the culprit vessel in non-ST elevation myocardial infarction. Arch Med Sci Atheroscler Dis. 2020;5:e226 – 9 . [97] Morris N, Reynard C, Body R. The low accuracy of the non-ST-elevation myocardial infarction electrocardiograph criteria of the fourth universal de ﬁ nition of myocardial infarction. Hong Kong J Emerg Med. 2020;27:229 – 35 . [98] Somers MP, Brady WJ, Perron AD, Mattu A. The prominent T wave: electrocardiographic differential diagnosis. Am J Med. 2002;20:243 – 51 . [99] Schläpfer J, Wellens HJ. Computer-interpreted electrocardiograms: bene ﬁ ts and limitations. J Am Coll Cardiol. 2017;70:1183 – 92 . [100] Wang Z, Stavrakis S, Yao B. Hierarchical deep learning with Generative Adversarial Network for automatic cardiac diagnosis from ECG signals. Comput Biol Med. 2023;155:106641 . [101] Vylegzhanina AV, Kogan AE, Katrukha IA, Koshkina EV, Bereznikova AV, Filatov VL, et al. Full-size and partially truncated cardiac troponin complexes in the blood of patients with acute myocardial infarction. Clin Chem. 2019;65:882 – 92 . [102] Katrukha IA, Katrukha AG. Myocardial injury and the release of troponins I and T in the blood of patients. Clin Chem. 2021;67:124 – 30 . [103] Thygesen K, Alpert JS, Jaffe AS, Simoons ML, Chaitman BR, White HD, et al. Third universal de ﬁ nition of myocardial infarction. J Am Coll Cardiol. 2012;60:1581 – 98 . [104] Zhelev Z, Hyde C, Youngman E, Rogers M, Fleming S, Slade T, et al. Diagnostic accuracy of single baseline measurement of Elecsys Troponin T high-sensitive assay for diagnosis of acute myocardial infarction in emergency department: systematic review and meta-analysis. BMJ. 2015;350:h15 . [105] Pickering JW, Than MP, Cullen L, Aldous S, Ter Avest E, Body R, et al. Rapid rule-out of acute myocardial infarction with a single highsensitivity cardiac troponin T measurement below the limit of detection: a collaborative meta-analysis. Ann Intern Med. 2017;166:715 – 24 . [106] Neumann JT, Twerenbold R, Ojeda F, Sörensen NA, Chapman AR, Shah ASV, et al. Application of high-sensitivity troponin in suspected myocardial infarction. N Engl J Med. 2019;380:2529 – 40 . [107] Sandoval Y, Smith SW, Schulz KM, Murakami MM, Love SA, Nicholson J, et al. Diagnosis of type 1 and type 2 myocardial infarction using a high-sensitivity cardiac troponin I assay with sex-speci ﬁ c 99th percentiles based on the third universal de ﬁ nition of myocardial infarction classi ﬁ cation system. Clin Chem. 2015;61:657 – 63 . [108] Aw T-C, Phua S-K, Tan S-P. Measurement of cardiac troponin I in serum with a new high-sensitivity assay in a large multi-ethnic Asian cohort and the impact of gender. Clin Chim Acta. 2013;422:26 – 8 . [109] Shah AS, Grif ﬁ ths M, Lee KK, McAllister DA, Hunter AL, Ferry AV, et al. High sensitivity cardiac troponin and the under-diagnosis of myocardial infarction in women: prospective cohort study. BMJ. 2015;350:g7873 . [110] Boeddinghaus J, Nestelberger T, Koechlin L, Wussler D, Lopez-Ayala P, Walter JE, et al. Early diagnosis of myocardial infarction with point-ofcare high-sensitivity cardiac troponin I. J Am Coll Cardiol. 2020;75: 1111 – 24 . [111] Apple FS, Smith SW, Greenslade JH, Sandoval Y, Parsonage W, Ranasinghe I, et al. Single high-sensitivity point-of-care whole-blood cardiac troponin I measurement to rule out acute myocardial infarction at low risk. Circulation. 2022;146:1918 – 29 . [112] Pickering JW, Young JM, George PM, Watson AS, Aldous SJ, Troughton RW, et al. Validity of a novel point-of-care troponin assay for single-test rule-out of acute myocardial infarction. JAMA Cardiol. 2018;3:1108 – 12 . [113] Sörensen NA, Neumann JT, Ojeda F, Giannitsis E, Spanuth E, Blankenberg S, et al. Diagnostic evaluation of a high-sensitivity troponin I point-of-care assay. Clin Chem. 2019;65:1592 – 601 . [114] Januzzi JL, Mahler SA, Christenson RH, Rymer J, Newby LK, Body R, et al. Recommendations for institutions transitioning to high-sensitivity troponin testing. J Am Coll Cardiol. 2019;73:1059 – 77 . [115] Aakre KM, Saenger AK, Body R, Collinson P, Hammarsten O, Jaffe AS, et al. Analytical considerations in deriving 99th percentile upper reference limits for high-sensitivity cardiac troponin assays: Educational recommendations from the IFCC Committee on Clinical Application of Cardiac Bio-Markers. Clin Chem. 2022;68:1022 – 30 . [116] Lee KK, Ferry AV, Anand A, Strachan FE, Chapman AR, Kimenai DM, et al. Sex-speci ﬁ c thresholds of high-sensitivity troponin in patients with suspected acute coronary syndrome. J Am Coll Cardiol. 2019;74:2032 – 43 . [117] Greene DN, Schmidt RL, Christenson RH, Rongitsch J, Imborek KL, Rebuck H, et al. Distribution of high-sensitivity cardiac troponin and Nterminal pro-brain natriuretic peptide in healthy transgender people. JAMA Cardiol. 2022;7:1170 – 4 . [118] Welsh P, Preiss D, Hayward C, Shah ASV, McAllister D, Briggs A, et al. Cardiac troponin T and troponin I in the general population. Circulation. 2019;139:2754 – 64 . [119] Hickman PE, Abhayaratna WP, Potter JM, Koerbin G. Age-related differences in hs-cTnI concentration in healthy adults. Clin Biochem. 2019;69:26 – 9 . [120] Welsh P, Preiss D, Shah ASV, McAllister D, Briggs A, Boachie C, et al. Comparison between high-sensitivity cardiac troponin T and cardiac troponin I in a large general population cohort. Clin Chem. 2018;64:1607 – 16 . [121] Collinson P, Aakre KM, Saenger A, Body R, Hammarsten O, Jaffe AS, et al. Cardiac troponin measurement at the point of care: educational recommendations on analytical and clinical aspects by the IFCC Committee on Clinical Applications of Cardiac Bio-Markers (IFCC C-CB). Clin Chem Lab Med. 2023;61:989 – 98 . [122] Collinson PO, Saenger AK, Apple FS. High sensitivity, contemporary and point-of-care cardiac troponin assays: educational aids developed by the IFCC Committee on Clinical Application of Cardiac Bio-Markers. Clin Chem Lab Med. 2019;57:623 – 32 . [123] Cullen L, Greenslade J, Parsonage W, Stephensen L, Smith SW, Sandoval Y, et al. Point-of-care high-sensitivity cardiac troponin in suspected acute myocardial infarction assessed at baseline and 2 h. Eur Heart J. 2024;45:2508 – 15 . [124] Ra ﬁ udeen R, Barlis P, White HD, Wv Gaal. Type 2 MI and myocardial injury in the era of high-sensitivity troponin. Eur Cardiol. 2022;17:e03 . [125] Sandoval Y, Apple FS, Smith SW. High-sensitivity cardiac troponin assays and unstable angina. Eur Heart J Acute Cardiovasc Care. 2018;7:120 – 8 . [126] Karády J, Mayrhofer T, Ferencik M, Nagurney JT, Udelson JE, Kammerlander AA, et al. Discordance of high-sensitivity troponin assays in patients with suspected acute coronary syndromes. J Am Coll Cardiol. 2021;77:1487 – 99 . [127] Rubini Gimenez M, Twerenbold R, Reichlin T, Wildi K, Haaf P, Schaefer M, et al. Direct comparison of high-sensitivity-cardiac troponin I vs. T for the early diagnosis of acute myocardial infarction. Eur Heart J. 2014;35:2303 – 11 . [128] Wens SC, Schaaf GJ, Michels M, Kruijshaar ME, van Gestel TJ, In ’ t Groen S, et al. Elevated plasma cardiac troponin T levels caused by skeletal muscle damage in Pompe disease. Circ Cardiovasc Genet. 2016;9:6 – 13 . [129] Schmid J, Liesinger L, Birner-Gruenberger R, Stojakovic T, Scharnagl H, Dieplinger B, et al. Elevated cardiac troponin T in patients with skeletal myopathies. J Am Coll Cardiol. 2018;71:1540 – 9 . [130] Stavroulakis GA, George KP. Exercise-induced release of troponin. Clin Cardiol. 2020;43:872 – 81 . [131] Aakre KM, Omland T. Physical activity, exercise and cardiac troponins: clinical implications. Prog Cardiovasc Dis. 2019;62:108 – 15 . [132] O ’ Lone E, Apple FS, Burton JO, Caskey FJ, Craig JC, deFilippi CR, et al. De ﬁ ning myocardial infarction in trials of people receiving hemodialysis: consensus report from the SONG-HD MI Expert Working group. Kidney Int. 2023;103:1028 – 37 . [133] Ammann P, P ﬁ sterer M, Fehr T, Rickli H. Raised cardiac troponins. BMJ. 2004;328:1028 – 9 . [134] Mair J, Lindahl B, Müller C, Giannitsis E, Huber K, Möckel M, et al. What to do when you question cardiac troponin values. Eur Heart J Acute Cardiovasc Care. 2018;7:577 – 86 . [135] Bohner J, von Pape KW, Hannes W, Stegmann T. False-negative immunoassay results for cardiac troponin I probably due to circulating troponin I autoantibodies. Clin Chem. 1996;42:2046 . [136] Jaffe AS, Lindahl B, Giannitsis E, Mueller C, Cullen L, Hammarsten O, et al. ESC study group on cardiac biomarkers of the Association for Acute CardioVascular Care: A fond farewell at the retirement of CKMB. Eur Heart J. 2021;42:2260 – 4 . [137] Brownlee E, Greenslade JH, Kelly AM, Meek RA, Parsonage WA, Cullen L. Snapshot of suspected acute coronary syndrome assessment processes in the emergency department: a national cross-sectional survey. Emerg Med Australas. 2023;35:261 – 8 . [138] Kwok CS, Bennett S, Azam Z, Welsh V, Potluri R, Loke YK, et al. Misdiagnosis of acute myocardial infarction: a systematic review of the literature. Critical Pathw Cardiol. 2021;20:155 – 62 . [139] Weinstock MB, Weingart S, Orth F, VanFossen D, Kaide C, Anderson J, et al. Risk for clinically relevant adverse cardiac events in patients with chest pain at hospital admission. JAMA Intern Med. 2015;175:1207 – 12 . [140] Mahmoud O, Mahmaljy H, Elias H, Campoverde EH, Youniss M, Stanton M, et al. A comparative 30-day outcome analysis of inpatient evaluation vs outpatient testing in patients presenting with chest pain in the high-sensitivity troponin era. A propensity score matched casecontrol retrospective study. Clin Cardiol. 2020;43:1248 – 54 . [141] Than M, Flaws D, Sanders S, Doust J, Glasziou P, Kline J, et al. Development and validation of the Emergency Department Assessment of Chest pain Score and 2 h accelerated diagnostic protocol. Emerg Med Australas. 2014;26:34 – 44 . [142] Collet JP, Thiele H, Barbato E, Barthelemy O, Bauersachs J, Bhatt DL, et al. 2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur Heart J. 2021;42:1289 – 367 . [143] Mueller C, Giannitsis E, Christ M, Ordóñez-Llanos J, deFilippi C, McCord J, et al. Multicenter evaluation of a 0-hour/1-hour algorithm in the diagnosis of myocardial infarction with high-sensitivity cardiac troponin T. Ann Emerg Med. 2016;68:76 – 87 . [144] Peacock WF, Christenson R, Diercks DB, Fromm C, Headden GF, Hogan CJ, et al. Myocardial infarction can be safely excluded by highsensitivity troponin I resting 3 hours after emergency department presentation. Acad Emerg Med. 2020;27:671 – 80 . [145] Taggart C, Wereski R, Mills NL, Chapman AR. Diagnosis, investigation and management of patients with acute and chronic myocardial injury. J Clin Med. 2021;10:2331 . [146] Cohen B, Cohen S, Tor R, Shochat T, Fuchs S, Kornowski R, et al. Suspected non-ST-elevation acute coronary syndrome meeting rapid ruleout criteria: resource utilization, diagnostic yield, and clinical outcomes of hospital admission. Eur Heart J Qual Care Clin Outcomes. 2023;9:207 – 15 . [147] Anand A, Lee KK, Chapman AR, Ferry AV, Adamson PD, Strachan FE, et al. High-sensitivity cardiac troponin on presentation to rule out myocardial infarction: a stepped-wedge cluster randomized controlled trial. Circulation. 2021;143:2214 – 24 . [148] Neumann JT, Sörensen NA, Schwemer T, Ojeda F, Bourry R, Sciacca V, et al. Diagnosis of myocardial infarction using a high-sensitivity troponin I 1-hour algorithm. JAMA Cardiol. 2016;1:397 – 404 . [149] Boeddinghaus J, Nestelberger T, Twerenbold R, Wildi K, Badertscher P, Cupa J, et al. Direct comparison of 4 very early rule-out strategies for acute myocardial infarction using high-sensitivity cardiac troponin I. Circulation. 2017;135:1597 – 611 . [150] Chapman AR, Anand A, Boeddinghaus J, Ferry AV, Sandeman D, Adamson PD, et al. Comparison of the ef ﬁ cacy and safety of early ruleout pathways for acute myocardial infarction. Circulation. 2017;135: 1586 – 96 . [151] Cullen L, Mueller C, Parsonage WA, Wildi K, Greenslade JH, Twerenbold R, et al. Validation of high-sensitivity troponin I in a 2-hour diagnostic strategy to assess 30-day outcomes in emergency department patients with possible acute coronary syndrome. J Am Coll Cardiol. 2013;62:1242 – 9 . [152] Rubini Gimenez M, Twerenbold R, Jaeger C, Schindler C, Puelacher C, Wildi K, et al. One-hour rule-in and rule-out of acute myocardial infarction using high-sensitivity cardiac troponin I. Am J Med. 2015;128:861 – 70 . [153] Boeddinghaus J, Twerenbold R, Nestelberger T, Badertscher P, Wildi K, Puelacher C, et al. Clinical validation of a novel high-sensitivity cardiac troponin I assay for early dagnosis of acute myocardial infarction. Clin Chem. 2018;64:1347 – 60 . [154] Chapman AR, Fujisawa T, Lee KK, Andrews JP, Anand A, Sandeman D, et al. Novel high-sensitivity cardiac troponin I assay in patients with suspected acute coronary syndrome. Heart. 2019;105:616 – 22 . [155] Reichlin T, Schindler C, Drexler B, Twerenbold R, Reiter M, Zellweger C, 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 – 8 . [156] Bularga A, Lee KK, Stewart S, Ferry AV, Chapman AR, Marshall L, et al. High-sensitivity troponin and the application of risk strati ﬁ cation thresholds in patients with suspected acute coronary syndrome. Circulation. 2019;140:1557 – 68 . [157] Lee C-C, Huang S-S, Yeo YH, Hou Y-T, Park JY, Inoue K, et al. Highsensitivity-cardiac troponin for accelerated diagnosis of acute myocardial infarction: a systematic review and meta-analysis. Am J Med. 2020;38:1402 – 7 . [158] Westwood ME, Armstrong N, Worthy G, Fayter D, Ramaekers BLT, Grimm S, et al. Optimizing the use of high-sensitivity troponin assays for the early rule-out of myocardial infarction in patients presenting with chest pain: a systematic review. Clin Chem. 2021;67:237 – 44 . [159] Boeddinghaus J, Nestelberger T, Badertscher P, Twerenbold R, Fitze B, Wussler D, et al. Predicting acute myocardial infarction with a single blood draw. Clin Chem. 2019;65:437 – 50 . [160] Chapman AR, Sandeman D, Ferry AV, Stewart S, Strachan FE, Wereski R, et al. Risk strati ﬁ cation using high-sensitivity cardiac troponin T in patients with suspected acute coronary syndrome. J Am Coll Cardiol. 2020;75:985 – 7 . [161] Body R, Carley S, McDowell G, Jaffe AS, France M, Cruickshank K, et al. Rapid exclusion of acute myocardial infarction in patients with undetectable troponin using a high-sensitivity assay. J Am Coll Cardiol. 2011;58:1332 – 9 . [162] Apple FS, Jesse RL, Newby LK, Wu AH, Christenson RH. National Academy of Clinical Biochemistry and IFCC Committee for Standardization of Markers of Cardiac Damage Laboratory Medicine Practice Guidelines: Analytical issues for biochemical markers of acute coronary syndromes. Circulation. 2007;115:e352 – 5 . [163] Bandstein N, Ljung R, Johansson M, Holzmann MJ. Undetectable highsensitivity cardiac troponin T level in the emergency department and risk of myocardial infarction. J Am Coll Cardiol. 2014;63:2569 – 78 . [164] Body R, Burrows G, Carley S, Cullen L, Than M, Jaffe AS, et al. Highsensitivity cardiac troponin T concentrations below the limit of detection to exclude acute myocardial infarction: a prospective evaluation. Clin Chem. 2015;61:983 – 9 . [165] Peacock WF, Baumann BM, Bruton D, Davis TE, Handy B, Jones CW, et al. Ef ﬁ cacy of high-sensitivity troponin T in identifying very-low-risk patients with possible acute coronary syndrome. JAMA Cardiol. 2018;3:104 – 11 . [166] Thygesen K, Mair J, Giannitsis E, Mueller C, Lindahl B, Blankenberg S, et al. How to use high-sensitivity cardiac troponins in acute cardiac care. Eur Heart J. 2012;33:2252 – 7 . [167] Reichlin T, Twerenbold R, Wildi K, Gimenez MR, Bergsma N, Haaf P, et al. Prospective validation of a 1-hour algorithm to rule-out and rule-in acute myocardial infarction using a high-sensitivity cardiac troponin T assay. CMAJ. 2015;187:E243 . [168] Body R, Mueller C, Giannitsis E, Christ M, Ordonez-Llanos J, de Filippi CR, et al. The use of very low concentrations of high-sensitivity troponin T to rule out acute myocardial infarction using a single blood test. Acad Emerg Med. 2016;23:1004 – 13 . [169] Greenslade J, Cho E, Van Hise C, Hawkins T, Parsonage W, Ungerer J, et al. Evaluating rapid rule-out of acute myocardial infarction using a high-sensitivity cardiac troponin I assay at presentation. Clin Chem. 2018;64:820 – 9 . [170] Shah AS, Anand A, Sandoval Y, Lee KK, Smith SW, Adamson PD, et al. High-sensitivity cardiac troponin I at presentation in patients with suspected acute coronary syndrome: a cohort study. Lancet. 2015;386:2481 – 8 . [171] Than MP, Aldous SJ, Troughton RW, Pemberton CJ, Richards AM, Frampton CMA, et al. Detectable high-sensitivity cardiac troponin within the population reference interval conveys high 5-year cardiovascular risk: an observational study. Clin Chem. 2018;64:1044 – 53 . [172] Keller T, Zeller T, Peetz D, Tzikas S, Roth A, Czyz E, et al. Sensitive troponin I assay in early diagnosis of acute myocardial infarction. N Engl J Med. 2009;361:868 – 77 . [173] Chew DP, Lambrakis K, Blyth A, Seshadri A, Edmonds MJR, Briffa T, et al. A randomized trial of a 1-hour troponin T protocol in suspected acute coronary syndromes: the Rapid Assessment of Possible Acute Coronary Syndrome in the Emergency Department With HighSensitivity Troponin T Study (RAPID-TnT). Circulation. 2019;140: 1543 – 56 . [174] Nowak RM, Christenson RH, Jacobsen G, McCord J, Apple FS, Singer AJ, et al. Performance of novel high-sensitivity cardiac troponin I assays for 0/1-hour and 0/2- to 3-hour evaluations for acute myocardial infarction: results from the HIGH-US Study. Ann Emerg Med. 2020;76: 1 – 13 . [175] Stoyanov KM, Hund H, Biener M, Gandowitz J, Riedle C, Löhr J, et al. RAPID-CPU: a prospective study on implementation of the ESC 0/1- hour algorithm and safety of discharge after rule-out of myocardial infarction. Eur Heart J Acute Cardiovasc Care. 2020;9:39 – 51 . [176] IFCC Committee on Clinical Applications of Cardiac Bio-Markers (CCB). High-sensitivity cardiac troponin I and T assay analytical characteristics designated by manufacturer. Available at: ifcc ﬁ les.com/2024/ 03/High-Sensitivity-Cardiac-Troponin-I-and-T-Assay-Analytical-Chara cteristics-Designated-By-Manufacturer-v062024.pdf ; 2022. [177] Boeddinghaus J, Nestelberger T, Twerenbold R, Koechlin L, Meier M, Troester V, et al. High-sensitivity cardiac troponin I assay for early diagnosis of acute myocardial infarction. Clin Chem. 2019;65:893 – 904 . [178] Wildi K, Cullen L, Twerenbold R, Greenslade JH, Parsonage W, Boeddinghaus J, et al. Direct comparison of 2 rule-out strategies for acute myocardial infarction: 2-h accelerated diagnostic protocol vs 2-h algorithm. Clin Chem. 2017;63:1227 – 36 . [179] Boeddinghaus J, Nestelberger T, Twerenbold R, Neumann JT, Lindahl B, Giannitsis E, et al. Impact of age on the performance of the ESC 0/1halgorithms for early diagnosis of myocardial infarction. Eur Heart J. 2018;39:3780 – 94 . [180] Reichlin T, Irfan A, Twerenbold R, Reiter M, Hochholzer W, Burkhalter H, et al. Utility of absolute and relative changes in cardiac troponin concentrations in the early diagnosis of acute myocardial infarction. Circulation. 2011;124:136 – 45 . [181] Neumann JT, Sörensen NA, Rübsamen N, Ojeda F, Schock A, Seddighizadeh P, et al. Evaluation of a new ultra-sensitivity troponin I assay in patients with suspected myocardial infarction. Int J Cardiol. 2019;283:35 – 40 . [182] Boeddinghaus J, Reichlin T, Cullen L, Greenslade JH, Parsonage WA, Hammett C, et al. Two-hour algorithm for triage toward rule-out and rule-in of acute myocardial infarction by use of high-sensitivity cardiac troponin I. Clin Chem. 2016;62:494 – 504 . [183] Nestelberger T, Boeddinghaus J, Greenslade J, Parsonage WA, Than M, Wussler D, et al. Two-hour algorithm for rapid triage of suspected acute myocardial infarction using a high-sensitivity cardiac troponin I assay. Clin Chem. 2019;65:1437 – 47 . [184] Wildi K, Boeddinghaus J, Nestelberger T, Lopez-Ayala P, Yufera Sanchez A, Okamura B, et al. 0/2 h-algorithm for rapid triage of suspected myocardial infarction using a novel high-sensitivity cardiac troponin I assay. Clin Chem. 2021;68:303 – 12 . [185] Wildi K, Lopez-Ayala P, Koechlin L, Boeddinghaus J, Nestelberger T, Wussler D, et al. Validation of the novel European Society of Cardiology 0/2-hour algorithm using Hs-cTnT in the early diagnosis of myocardial infarction. Am J Cardiol. 2021;154:128 – 30 . [186] Chan Pin Yin D, Azzahha ﬁ J, James S. Risk assessment using risk scores in patients with acute coronary syndrome. J Clin Med. 2020;9:3039 . [187] Than M, Cullen L, Aldous S, Parsonage WA, Reid CM, Greenslade J, et al. 2-Hour accelerated diagnostic protocol to assess patients with chest pain symptoms using contemporary troponins as the only biomarker: the ADAPT trial. J Am Coll Cardiol. 2012;59:2091 – 8 . [188] Mahler SA, Riley RF, Hiestand BC, Russell GB, Hoekstra JW, Lefebvre CW, et al. The HEART pathway randomized trial, 8. Circ Cardiovasc Qual Outcomes; 2015;. p. 195 – 203 . [189] Cullen L, Greenslade JH, Hawkins T, Hammett C, O ’ Kane S, Ryan K, et al. Improved Assessment of Chest pain Trial (IMPACT): assessing patients with possible acute coronary syndromes. Med J Aust. 2017;207:195 – 200 . [190] Parsonage WA, Milburn T, Ashover S, Skoien W, Greenslade JH, McCormack L, et al. Implementing change: evaluating the Accelerated Chest pain Risk Evaluation (ACRE) project. Med J Aust. 2017;207:201 – 5 . [191] Mark DG, Huang J, Chettipally U, Kene MV, Anderson ML, Hess EP, et al. Performance of coronary risk scores among patients with chest pain in the emergency department. J Am Coll Cardiol. 2018;71:606 – 16 . [192] Stopyra JP, Miller CD, Hiestand BC, Lefebvre CW, Nicks BA, Cline DM, et al. Chest pain risk strati ﬁ cation: a comparison of the 2-Hour Accelerated Diagnostic Protocol (ADAPT) and the HEART Pathway. Critical Pathw Cardiol. 2016;15:46 – 9 . [193] Stopyra JP, Miller CD, Hiestand BC, Lefebvre CW, Nicks BA, Cline DM, et al. Validation of the no objective testing rule and comparison to the HEART pathway. Acad Emerg Med. 2017;24:1165 – 8 . [194] Stopyra JP, Riley RF, Hiestand BC, Russell GB, Hoekstra JW, Lefebvre CW, et al. The HEART pathway randomized controlled trial one-year outcomes. Acad Emerg Med. 2019;26:41 – 50 . [195] Chapman AR, Hesse K, Andrews J, Ken Lee K, Anand A, Shah ASV, et al. High-sensitivity cardiac troponin I and clinical risk scores in patients with suspected acute coronary syndrome. Circulation. 2018;138:1654 – 65 . [196] Khan E, Lambrakis K, Blyth A, Seshadri A, Edmonds MJR, Briffa T, et al. Classi ﬁ cation performance of clinical risk scoring in suspected acute coronary syndrome beyond a rule-out troponin pro ﬁ le. Eur Heart J Acute Cardiovasc Care. 2021;10:1038 – 47 . [197] Bank IEM, de Hoog VC, de Kleijn DPV, Pasterkamp G, Doevendans PA, den Ruijter HM, et al. Sex-based differences in the performance of the HEART Score in patients presenting to the emergency department with acute chest pain. J Am Heart Assoc. 2017;6:e005373 . [198] Greenslade JH, Parsonage W, Foran L, McCormack L, Ashover S, Milburn T, et al. Widespread introduction of a high-sensitivity troponin assay: assessing the impact on patients and health services. J Clin Med. 2020;9(6):1883 . [199] Ambavane A, Lindahl B, Giannitsis E, Roiz J, Mendivil J, Frankenstein L, et al. Economic evaluation of the one-hour rule-out and rule-in algorithm for acute myocardial infarction using the high-sensitivity cardiac troponin T assay in the emergency department. PLoS One. 2017;12: e0187662 . [200] Ljung L, Lindahl B, Eggers KM, Frick M, Linder R, Löfmark HB, et al. A rule-out strategy based on high-sensitivity troponin and HEART Score reduces hospital admissions. Ann Emerg Med. 2019;73:491 – 9 . [201] Twerenbold R, Jaeger C, Rubini Gimenez M, Wildi K, Reichlin T, Nestelberger T, et al. Impact of high-sensitivity cardiac troponin on use of coronary angiography, cardiac stress testing, and time to discharge in suspected acute myocardial infarction. Eur Heart J. 2016;37:3324 – 32 . [202] Westwood M, Ramaekers B, Grimm S, Worthy G, Fayter D, Armstrong N, et al. High-sensitivity troponin assays for early rule-out of acute myocardial infarction in people with acute chest pain: a systematic review and economic evaluation. Health Technol Assess. 2021;25:1 – 276 . [203] Mueller-Hennessen M, Lindahl B, Giannitsis E, Biener M, Vafaie M, deFilippi CR, et al. Diagnostic and prognostic implications using age- and gender-speci ﬁ c cut-offs for high-sensitivity cardiac troponin T - Sub-analysis from the TRAPID-AMI study. Int J Cardiol. 2016;209:26 – 33 . [204] Canto JG, Rogers WJ, Goldberg RJ, Peterson ED, Wenger NK, Vaccarino V, et al. Association of age and sex with myocardial infarction symptom presentation and in-hospital mortality. JAMA. 2012;307:813 – 22 . [205] Hillinger P, Twerenbold R, Wildi K, Rubini Gimenez M, Jaeger C, Boeddinghaus J, et al. Gender-speci ﬁ c uncertainties in the diagnosis of acute coronary syndrome. Clin Res Cardiol. 2017;106:28 – 37 . [206] Twerenbold R, Badertscher P, Boeddinghaus J, Nestelberger T, Wildi K, Puelacher C, et al. 0/1-Hour triage algorithm for mocardial infarction in patients with renal dysfunction. Circulation. 2018;137:436 – 51 . [207] Miller-Hodges E, Anand A, Shah ASV, Chapman AR, Gallacher P, Lee KK, et al. High-sensitivity cardiac troponin and the risk strati ﬁ cation of patients with renal impairment presenting with suspected acute coronary syndrome. Circulation. 2018;137:425 – 35 . [208] Greenslade JH, Berndt S, Stephensen L, Starmer K, Starmer G, Parsonage W, et al. Value of single troponin values in the emergency department for excluding acute myocardial infarction in Aboriginal and Torres Strait Islander people. Med J Aust. 2022;217:48 – 9 . [209] Bodapati SN, Gunnarsson R, McBride WJ, Stone R, Sutcliffe S. Chest pain risk assessment in Indigenous and non-Indigenous Australians using HEART Score. Emerg Med Australas. 2016;28:138 – 44 . [210] Agostino JW, Wong D, Paige E, Wade V, Connell C, Davey ME, et al. Cardiovascular disease risk assessment for Aboriginal and Torres Strait Islander adults aged under 35 years: a consensus statement. Med J Aust. 2020;212:422 – 7 . [211] Cullen L, Stephensen L, Greenslade J, Starmer K, Starmer G, Stone R, et al. Emergency department assessment of suspected acute coronary syndrome using the IMPACT Pathway in Aboriginal and Torres Strait Islander People. Heart Lung Circ. 2022;31:1029 – 36 . [212] deFilippi C, Seliger SL, Kelley W, Duh SH, Hise M, Christenson RH, et al. Interpreting cardiac troponin results from high-sensitivity assays in chronic kidney disease without acute coronary syndrome. Clin Chem. 2012;58:1342 – 51 . [213] Doudesis D, Lee KK, Bularga A, Ferry AV, Tuck C, Anand A, et al. Machine learning to optimise use of cardiac troponin in the diagnosis of acute myocardial infarction. Eur Heart J. 2022;43:1201 – 10 . [214] Than MP, Pickering JW, Sandoval Y, Shah ASV, Tsanas A, Apple FS, et al. Machine learning to predict the likelihood of acute myocardial infarction. Circulation. 2019;140:899 – 909 . [215] Neumann JT, Twerenbold R, Ojeda F, Aldous SJ, Allen BR, Apple FS, et al. Personalized diagnosis in suspected myocardial infarction. Clin Res Cardiol. 2023;9:1288 – 301 . [216] Antithrombotic Trialists Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ. 2002;324:71 – 86 . [217] 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 . [218] Reilly IA, FitzGerald GA. Inhibition of thromboxane formation in vivo and ex vivo: implications for therapy with platelet inhibitory drugs. Blood. 1987;69:180 – 6 . [219] Hofmann R, James SK, Jernberg T, Lindahl B, Erlinge D, Witt N, et al. Oxygen therapy in suspected acute myocardial infarction. N Engl J Med. 2017;377:1240 – 9 . [220] Stewart RAH, Jones P, Dicker B, Jiang Y, Smith T, Swain A, et al. High ﬂ ow oxygen and risk of mortality in patients with a suspected acute coronary syndrome: pragmatic, cluster randomised, crossover trial. BMJ. 2021;372:n355 . [221] Chu DK, Kim LH, Young PJ, Zamiri N, Almenawer SA, Jaeschke R, et al. Mortality and morbidity in acutely ill adults treated with liberal versus conservative oxygen therapy (IOTA): a systematic review and metaanalysis. Lancet. 2018;391:1693 – 705 . [222] Cabello JB, Burls A, Emparanza JI, Bayliss S, Quinn T. Oxygen therapy for acute myocardial infarction. Cochrane Database Syst Rev. 2016;12:CD007160 . [223] Stub D, Smith K, Bernard S, Nehme Z, Stephenson M, Bray JE, et al. Air versus oxygen in ST-segment-elevation myocardial infarction. Circulation. 2015;131:2143 – 50 . [224] Hofmann R, James SK, Svensson L, Witt N, Frick M, Lindahl B, et al. DETermination of the role of OXygen in suspected acute myocardial infarction trial. Am Heart J. 2014;167:322 – 8 . [225] ISIS-4 (Fourth International Study of Infarct Survival) Collaborative Group. ISIS-4: A randomised factorial trial assessing early oral captopril, oral mononitrate, and intravenous magnesium sulphate in 58 050 patients with suspected acute myocardial infarction. Lancet. 1995;345:669 – 85 . [226] Italian Group for the Study of Survival in Myocardial Infarction. GISSI3: effects of lisinopril and transdermal glyceryl trinitrate singly and together on 6-week mortality and ventricular function after acute myocardial infarction. Lancet. 1994;343:1115 – 22 . [227] Duarte GS, Nunes-Ferreira A, Rodrigues FB, Pinto FJ, Ferreira JJ, Costa J, et al. Morphine in acute coronary syndrome: systematic review and meta-analysis. BMJ Open. 2019;9:e025232 . [228] Iglesias JF, Valgimigli M, Carbone F, Lauriers N, Masci PG, Degrauwe S. Effects of fentanyl versus morphine on ticagrelor-induced platelet inhibition in patients with ST-segment elevation myocardial infarction. Circulation. 2020;142:2479 – 81 . [229] Ghadban R, Enezate T, Payne J, Allaham H, Halawa A, Fong HK, et al. The safety of morphine use in acute coronary syndrome: a meta-analysis. Heart Asia. 2019;11:e011142 . [230] Parodi G, Bellandi B, Xanthopoulou I, Capranzano P, Capodanno D, Valenti R, et al. Morphine is associated with a delayed activity of oral antiplatelet agents in patients with ST-elevation acute myocardial infarction undergoing primary percutaneous coronary intervention. Circ Cardiovasc Interv. e001593. [231] Lapostolle F, van ’ t Hof AW, Hamm CW, Stibbe O, Ecollan P, Collet J-P, et al. Morphine and ticagrelor interaction in primary percutaneous coronary intervention in ST-segment elevation myocardial infarction: ATLANTIC-morphine. Am J Cardiovasc Drugs. 2019;19:173 – 83 . [232] Kubica J, Adamski P, Ostrowska M, Sikora J, Kubica JM, Sroka WD, 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 – 52 . [233] Gislason GH, Jacobsen S, Rasmussen JN, Rasmussen S, Buch P, Friberg J, et al. Risk of death or reinfarction associated with the use of selective cyclooxygenase-2 inhibitors and nonselective nonsteroidal antiinﬂ ammatory drugs after acute myocardial infarction. Circulation. 2006;113:2906 – 13 . [234] Kearney PM, Baigent C, Godwin J, Halls H, Emberson JR, Patrono C. Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal antiin ﬂ ammatory drugs increase the risk of atherothrombosis? Metaanalysis of randomised trials. BMJ. 2006;332:1302 – 8 . [235] Melki D, Lugnegård J, Alfredsson J, Lind S, Eggers KM, Lindahl B, et al. Implications of introducing high-sensitivity cardiac troponin t into clinical practice: Data from the SWEDEHEART registry. J Am Coll Cardiol. 2015;65:1655 – 64 . [236] Celik S, Giannitsis E, Wollert KC, Schwöbel K, Lossnitzer D, Hilbel T, et al. Cardiac troponin T concentrations above the $99^{\mathrm{th}}$ percentile value as measured by a new high-sensitivity assay predict long-term prognosis in patients with acute coronary syndromes undergoing routine early invasive strategy. Clin Res Cardiol. 2011;100:1077 – 85 . [237] Hermann LK, Weingart SD, Duvall WL, Henzlova MJ. The limited utility of routine cardiac stress testing in emergency department chest pain patients younger than 40 years. Ann Emerg Med. 2009;54:12 – 6 . [238] Greenslade JH, Parsonage W, Ho A, Scott A, Dalton E, Hammett C, et al. Utility of routine exercise stress testing among intermediate risk chest pain patients attending an emergency department. Heart Lung Circ. 2015;24:879 – 84 . [239] Sandoval Y, Apple FS, Mahler SA, Body R, Collinson PO, Jaffe AS. Highsensitivity cardiac troponin and the 2021 AHA/ACC/ASE/CHEST/ SAEM/SCCT/SCMR Guidelines for the evaluation and diagnosis of acute chest pain. Circulation. 2022;146:569 – 81 . [240] Mowatt G, Cook JA, Hillis GS, Walker S, Fraser C, Jia X, et al. 64-Slice computed tomography angiography in the diagnosis and assessment of coronary artery disease: systematic review and meta-analysis. Heart. 2008;94:1386 – 93 . [241] von Ballmoos MW, Haring B, Juillerat P, Alkadhi H. Meta-analysis: diagnostic performance of low-radiation-dose coronary computed tomography angiography. Ann Intern Med. 2011;154:413 – 20 . [242] Hulten EA, Carbonaro S, Petrillo SP, Mitchell JD, Villines TC. Prognostic value of cardiac computed tomography angiography: a systematic review and meta-analysis. J Am Coll Cardiol. 2011;57:1237 – 47 . [243] Andreini D, Pontone G, Mushtaq S, Bartorelli AL, Bertella E, Antonioli L, et al. A long-term prognostic value of coronary CT angiography in suspected coronary artery disease. JACC: Cardiovasc Imaging. 2012;5:690 – 701 . [244] Budoff MJ, Dowe D, Jollis JG, Gitter M, Sutherland J, Halamert E, et al. Diagnostic performance of 64-multidetector row coronary computed tomographic angiography for evaluation of coronary artery stenosis in individuals without known coronary artery disease: results from the prospective multicenter ACCURACY (Assessment by Coronary Computed Tomographic Angiography of Individuals Undergoing Invasive Coronary Angiography) trial. J Am Coll Cardiol. 2008;52:1724 – 32 . [245] Samad Z, Hakeem A, Mahmood SS, Pieper K, Patel MR, Simel DL, et al. A meta-analysis and systematic review of computed tomography angiography as a diagnostic triage tool for patients with chest pain presenting to the emergency department. J Nucl Cardiol. 2012;19:364 – 76 . [246] Kontos MC, de Lemos JA, Deitelzweig SB, Diercks DB, Gore MO, Hess EP, et al. 2022 ACC expert consensus decision pathway on the evaluation and disposition of acute chest pain in the emergency department: a report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol. 2022;80:1925 – 60 . [247] Zito A, Galli M, Biondi-Zoccai G, Abbate A, Douglas PS, Princi G, et al. Diagnostic strategies for the assessment of suspected stable coronary artery disease: a systematic review and meta-analysis. Ann Intern Med. 2023;176:817 – 26 . [248] Genders TS, Petersen SE, Pugliese F, Dastidar AG, Fleischmann KE, Nieman K, et al. The optimal imaging strategy for patients with stable chest pain: a cost-effectiveness analysis. Ann Emerg Med. 2015;162:474 – 84 . [249] Alexander M, Lan NSR, Dallo MJ, Briffa TG, San ﬁ lippo FM, Hooper A, et al. Clinical outcomes and health care costs of transferring rural Western Australians for invasive coronary angiography, and a costeffective alternative care model: a retrospective cross-sectional study. Med J Aust. 2023;219:155 – 61 . [250] Scott AC, McDonald A, Roberts T, Martin C, Manns T, Webster M, et al. Cardiovascular telemedicine program in rural Australia. N Engl J Med. 2020;383:883 – 4 . [251] Cho KK, French JK, Figtree GA, Chow CK, Kozor R. Rapid access chest pain clinics in Australia and New Zealand. Med J Aust. 2023;219:168 – 72 . [252] Tenkorang JN, Fox KF, Collier TJ, Wood DA. A rapid access cardiology service for chest pain, heart failure and arrhythmias accurately diagnoses cardiac disease and identi ﬁ es patients at high risk: a prospective cohort study. Heart. 2006;92:1084 – 90 . [253] Kozor R, Mooney J, Lowe H, Kritharides L, Altman M, Klimis H, et al. Rapid access chest pain clinics: an Australian cost-bene ﬁ t study. Heart Lung Circ. 2022;31:177 – 82 . [254] Black JA, Cheng K, Flood JA, Hamilton G, Parker S, Enayati A, et al. Evaluating the bene ﬁ ts of a rapid access chest pain clinic in Australia. Med J Aust. 2019;210:321 – 5 . [255] Yu C, Brazete S, Gullick J, Garcia MT, Brieger D, Kritharides L, et al. Long-term outcomes following rapid access chest pain clinic assessment: ﬁ rst Australian data. Heart Lung Circ. 2021;30:1309 – 13 . [256] Klimis H, Khan ME, Thiagalingam A, Bartlett M, Altman M, Wynne D, et al. Rapid access cardiology (RAC) services within a large tertiary referral centre — ﬁ rst year in review. Heart Lung Circ. 2018;27:1381 – 7 . [257] Klimis H, Thiagalingam A, Altman M, Atkins E, Figtree G, Lowe H, et al. Rapid-access cardiology services: can these reduce the burden of acute chest pain on Australian and New Zealand health services? Intern Med J. 2017;47:986 – 91 . [258] Wen LS, Espinola JA, Kosowsky JM, Camargo CA Jr. Do emergency department patients receive a pathological diagnosis? A nationallyrepresentative sample. West J Emerg Med. 2015;16:50 – 4 . [259] Sawatzky JA, Christie S, Singal RK. Exploring outcomes of a nurse practitioner-managed cardiac surgery follow-up intervention: a randomized trial. J Adv Nurs. 2013;69:2076 – 87 . [260] Musey Jr PI, Patel R, Fry C, Jimenez G, Koene R, Kline JA. Anxiety associated with increased risk for emergency department recidivism in patients with low-risk chest pain. Am J Cardiol. 2018;122:1133 – 41 . [261] Dennison Himmelfarb CR, Koirala B, Coke LA. Shared decision making: partnering with patients to improve cardiovascular care and outcomes. Journal of Cardiovascular Nursing. 2018;33:301 – 3 . [262] Klein LW, Anderson HV, Cigarroa J. Shared decision-making in cardiovascular practice. Cardiology in Review. 2023;31:52 – 6 . [263] Turkson-Ocran RN, Ogunwole SM, Hines AL, Peterson PN. Shared decision making in cardiovascular patient care to address cardiovascular disease disparities. Journal of the American Heart Association. 2021;10: e018183 . [264] Tideman PA, Tirimacco R, Senior DP, Setchell JJ, Huynh LT, Tavella R, et al. Impact of a regionalised clinical cardiac support network on mortality among rural patients with myocardial infarction. Med J Aust. 2014;200:157 – 60 . [265] Puymirat E, Simon T, Steg PG, Schiele F, Guéret P, Blanchard D, et al. Association of changes in clinical characteristics and management with improvement in survival among patients with ST-elevation myocardial infarction. JAMA. 2012;308:998 – 1006 . [266] Jollis JG, Granger CB, Henry TD, Antman EM, Berger PB, Moyer PH, et al. Systems of care for ST-segment-elevation myocardial infarction: a report from the American Heart Association ’ s Mission: Lifeline, 5. Circ Cardiovasc Qual Outcomes; 2012;. p. 423 – 8 . [267] Postma S, Bergmeijer T, ten Berg J, van ’ t Hof A. Pre-hospital diagnosis, triage and treatment in patients with ST elevation myocardial infarction. Heart. 2012;98:1674 – 8 . [268] Patel M, Dunford JV, Aguilar S, Castillo E, Patel E, Fisher R, et al. Prehospital electrocardiography by emergency medical personnel: effects on scene and transport times for chest pain and ST-segment elevation myocardial infarction patients. J Am Coll Cardiol. 2012;60:806 – 11 . [269] Amsterdam EA, Wenger NK, Brindis RG, Casey DE Jr, Ganiats TG, Holmes DR Jr, 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. J Am Coll Cardiol. 2014;64:e139 – 228 . [270] O ’ Gara PT, Kushner FG, Ascheim DD, Casey DE, Chung MK, de Lemos JA, et al. 2013 ACCF/AHA Guideline for the management of STelevation myocardial infarction. Circulation. 2013;127(4):e362 – 425 . [271] Knuuti J, Wijns W, Saraste A, Capodanno D, Barbato E, FunckBrentano C, et al. 2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes. Eur Heart J. 2020;41:407 – 77 . [272] Demandt JPA, Zelis JM, Koks A, Smits GHJM, Harst Pvd, Tonino PAL, et al. Prehospital risk assessment in patients suspected of non-STsegment elevation acute coronary syndrome: a systematic review and meta-analysis. BMJ Open. 2022;12:e057305 . [273] Harskamp RE, Laeven SC, Himmelreich JC, Lucassen WAM, Weert HCPMv. Chest pain in general practice: a systematic review of prediction rules. BMJ Open. 2019;9:e027081 . [274] Thompson SC, Nedkoff L, Katzenellenbogen J, Hussain MA, San ﬁ lippo F. Challenges in managing acute cardiovascular diseases and follow up care in rural areas: a narrative review. Int J Environ Res Public Health. 2019;16:1 – 17 . [275] Chew DP, French J, Briffa TG, Hammett CJ, Ellis CJ, Ranasinghe I, et al. Acute coronary syndrome care across Australia and New Zealand: the SNAPSHOT ACS study. Med J Aust. 2013;199:185 – 91 . [276] Brieger DB, Chew DP, Redfern J, Ellis C, Briffa TG, Howell TE, et al. Survival after an acute coronary syndrome: 18-month outcomes from the Australian and New Zealand SNAPSHOT ACS study. Med J Aust. 2015;203:368 . [277] Alston L, Allender S, Peterson K, Jacobs J, Nichols M. Rural inequalities in the Australian burden of ischaemic heart disease: a systematic review. Heart Lung Circ. 2017;26:122 – 33 . [278] Norman T, Young J, Jones JS, Egan G, Pickering J, Toit SD, et al. Implementation and evaluation of a rural general practice assessment pathway for possible cardiac chest pain using point-of-care troponin testing: a pilot study. BMJ Open. 2022;12:e044801 . [279] Zijlstra F, Hoorntje JCA, de Boer M-J, Reiffers S, Miedema K, Ottervanger JP, et al. Long-term bene ﬁ t of primary angioplasty as compared with thrombolytic therapy for acute myocardial infarction. N Engl J Med. 1999;341:1413 – 9 . [280] 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 . [281] Widimský P, Bude sínský T, Vorá c D, Groch L, Zelízko M, Aschermann M, 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 . [282] Andersen HR, Nielsen TT, Rasmussen K, Thuesen L, Kelbaek H, Thayssen P, et al. A comparison of coronary angioplasty with ﬁ brinolytic therapy in acute myocardial infarction. N Engl J Med. 2003;349:733 – 42 . [283] Boersma E. Does time matter? A pooled analysis of randomized clinical trials comparing primary percutaneous coronary intervention and inhospital ﬁ brinolysis in acute myocardial infarction patients. Eur Heart J. 2006;27:779 – 88 . [284] Gierlotka M, Gasior M, Wilczek K, Hawranek M, Szkodzinski J, Paczek P, et al. Reperfusion by primary percutaneous coronary intervention in patients with ST-segment elevation myocardial infarction within 12 to 24 hours of the onset of symptoms (from a prospective national observational study [PL-ACS]). Am J Cardiol. 2011;107:501 – 8 . [285] Busk M, Kaltoft A, Nielsen SS, Bøttcher M, Rehling M, Thuesen L, et al. Infarct size and myocardial salvage after primary angioplasty in patients presenting with symptoms for , 12 h vs. 12 – 72 h. Eur Heart J. 2009;30:1322 – 30 . [286] Schömig A, Mehilli J, Antoniucci D, Ndrepepa G, Markwardt C, Di Pede F, et al. Mechanical reperfusion in patients with acute myocardial infarction presenting more than 12 hours from symptom onset: a randomized controlled trial. JAMA. 2005;293:2865 – 72 . [287] Ndrepepa G, Kastrati A, Mehilli J, Antoniucci D, Schömig A. Mechanical reperfusion and long-term mortality in patients with acute myocardial infarction presenting 12 to 48 hours from onset of symptoms. JAMA. 2009;301:487 – 8 . [288] Ibanez B, James S, Agewall S, Antunes MJ, Bucciarelli-Ducci C, Bueno H, et al. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Rev Esp Cardiol (Engl Ed). 2017;70:1082 . [289] Fibrinolytic Therapy Trialists ’ (FTT) Collaborative Group. Indications for ﬁ brinolytic 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 – 22 . [290] Pinto DS, Frederick PD, Chakrabarti AK, Kirtane AJ, Ullman E, Dejam A, et al. Bene ﬁ t of transferring ST-segment – elevation myocardial infarction patients for percutaneous coronary intervention compared with administration of onsite ﬁ brinolytic declines as delays increase. Circulation. 2011;124:2512 – 21 . [291] Steg PG, Bonnefoy E, Chabaud S, Lapostolle F, Dubien PY, Cristo ﬁ ni P, et al. Impact of time to treatment on mortality after prehospital ﬁ brinolysis or primary angioplasty: data from the CAPTIM randomized clinical trial. Circulation. 2003;108:2851 – 6 . [292] Boersma E, Maas ACP, Deckers JW, Simoons ML. Early thrombolytic treatment in acute myocardial infarction: reappraisal of the golden hour. Lancet. 1996;348:771 – 5 . [293] Hochman JS, Reynolds HR, D zavík V, Buller CE, Ruzyllo W, Sadowski ZP, et al. Long-term effects of percutaneous coronary intervention of the totally occluded infarct-related artery in the subacute phase after myocardial infarction. Circulation. 2011;124:2320 – 8 . [294] Menon V, Pearte CA, Buller CE, Steg PG, Forman SA, White HD, et al. Lack of bene ﬁ t from percutaneous intervention of persistently occluded infarct arteries after the acute phase of myocardial infarction is time independent: insights from Occluded Artery Trial. Eur Heart J. 2009;30:183 – 91 . [295] Ioannidis JPA, Katritsis DG. Percutaneous coronary intervention for late reperfusion after myocardial infarction in stable patients. Am Heart J. 2007;154:1065 – 71 . [296] Armstrong PW, Gershlick AH, Goldstein P, Wilcox R, Danays T, Lambert Y, et al. Fibrinolysis or primary PCI in ST-segment elevation myocardial infarction. N Engl J Med. 2013;368:1379 – 87 . [297] Morrison LJ, Verbeek PR, McDonald AC, Sawadsky BV, Cook DJ. Mortality and prehospital thrombolysis for acute myocardial infarction a meta-analysis. JAMA. 2000;283:2686 – 92 . [298] Armstrong PW, Zheng Y, Westerhout CM, Rosell-Ortiz F, Sinnaeve P, Lambert Y, et al. Reduced dose tenecteplase and outcomes in elderly STsegment elevation myocardial infarction patients: Insights from the STrategic Reperfusion Early After Myocardial infarction trial. Am Heart J. 2015;169:890 – 8 . [299] Werf FVd, Risti c AD, Averkov OV, Arias-Mendoza A, Lambert Y, Saraiva JFK, et al. STREAM-2: Half-dose tenecteplase or primary percutaneous coronary intervention in older patients with ST-segment – elevation myocardial infarction: A randomized, open-label trial. Circulation. 2023;148:753 – 64 . [300] Terkelsen CJ, Sørensen JT, Maeng M, Jensen LO, Tilsted HH, Trautner S, et al. System delay and mortality among patients with STEMI treated with primary percutaneous coronary intervention. JAMA. 2010;304:763 – 71 . [301] Nallamothu BK, Normand SL, Wang Y, Hofer TP, Brush JE Jr, Messenger JC, et al. Relation between door-to-balloon times and mortality after primary percutaneous coronary intervention over time: a retrospective study. Lancet. 2015;385:1114 – 22 . [302] Squire BT, Tamayo-Sarver JH, Rashi P, Koenig W, Niemann JT. Effect of prehospital cardiac catheterization lab activation on door-to-balloon time, mortality, and false-positive activation. Prehosp Emerg Care. 2014;18:1 – 8 . [303] Mehta SR, Jolly SS, Cairns J, Niemela K, Rao SV, Cheema AN, et al. Effects of radial versus femoral artery access in patients with acute coronary syndromes with or without ST-segment elevation. J Am Coll Cardiol. 2012;60:2490 – 9 . [304] Shah R, Khan B. The MATRIX trial. Lancet. 2019;393:1803 . [305] Jolly SS, Yusuf S, Cairns J, Niemelä K, Xavier D, Widimsky P, et al. Radial versus femoral access for coronary angiography and intervention in patients with acute coronary syndromes (RIVAL): a randomised, parallel group, multicentre trial. Lancet. 2011;377:1409 – 20 . [306] Romagnoli E, Biondi-Zoccai G, Sciahbasi A, Politi L, Rigattieri S, Pendenza G, et al. Radial versus femoral randomized investigation in ST-segment elevation acute coronary syndrome: The RIFLE-STEACS (Radial Versus Femoral Randomized Investigation in ST-Elevation Acute Coronary Syndrome) Study. J Am Coll Cardiol. 2012;60: 2481 – 9 . [307] Gargiulo G, Giacoppo D, Jolly SS, Cairns J, Le May M, Bernat I, et al. Effects on mortality and major bleeding of radial versus femoral artery access for coronary angiography or percutaneous coronary intervention: a meta-analysis of individual patient data from 7 multicenter randomized clinical trials. Circulation. 1329 – 1343. [308] Lawton JS, Tamis-Holland JE, Bangalore S, Bates ER, Beckie TM, Bischoff JM, et al. 2021 ACC/AHA/SCAI Guideline for coronary artery revascularization: a report of the American College of Cardiology/ American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2021;145(3):e4 – 17 . [309] Barkagan M, Steinvil A, Berchenko Y, Finkelstein A, Keren G, Banai S, et al. Impact of routine manual aspiration thrombectomy on outcomes of patients undergoing primary percutaneous coronary intervention for acute myocardial infarction: A meta-analysis. Int J Cardiol. 2016;204:189 – 95 . [310] Fröbert O, Lagerqvist B, Olivecrona GK, Omerovic E, Gudnason T, Maeng M, et al. Thrombus aspiration during ST-degment elevation myocardial infarction. N Engl J Med. 2013;369:1587 – 97 . [311] Jolly SS, Cairns JA, Yusuf S, Meeks B, Pogue J, Rokoss MJ, et al. Randomized trial of primary PCI with or without routine manual thrombectomy. N Engl J Med. 2015;372:1389 – 98 . [312] National Guideline Centre. Evidence review for antiplatelet therapy for people with an ongoing separate indication for anticoagulation: Acute coronary syndrome: Evidence review G. London: National Institute for Health and Care Excellence (NICE); 2020 . [313] Räber L, Yamaji K, Kelbæk H, Engstrøm T, Baumbach A, Rof ﬁ M, et al. Five-year clinical outcomes and intracoronary imaging ﬁ ndings of the COMFORTABLE AMI trial: randomized comparison of biodegradable polymer-based biolimus-eluting stents with bare-metal stents in patients with acute ST-segment elevation myocardial infarction. Eur Heart J. 2019;40:1909 – 19 . [314] Sabaté M, Brugaletta S, Cequier A, Iñiguez A, Serra A, JiménezQuevedo P, et al. Clinical outcomes in patients with ST-segment elevation myocardial infarction treated with everolimus-eluting stents versus bare-metal stents (EXAMINATION): 5-year results of a randomised trial. Lancet. 2016;387:357 – 66 . [315] Bønaa KH, Mannsverk J, Wiseth R, Aaberge L, Myreng Y, Nygård O, et al. Drug-eluting or bare-metal stents for coronary artery disease. N Engl J Med. 2016;375:1242 – 52 . [316] Piccolo R, Bonaa KH, Efthimiou O, Varenne O, Baldo A, Urban P, et al. Drug-eluting or bare-metal stents for percutaneous coronary intervention: a systematic review and individual patient data meta-analysis of randomised clinical trials. Lancet. 2019;393:2503 – 10 . [317] Palmerini T, Benedetto U, Biondi-Zoccai G, Della Riva D, BacchiReggiani L, Smits PC, et al. Long-term safety of drug-eluting and baremetal stents: evidence from a comprehensive network meta-analysis. J Am Coll Cardiol. 2015;65:2496 – 507 . [318] Carrick D, Oldroyd KG, McEntegart M, Haig C, Petrie MC, Eteiba H, et al. A randomized trial of deferred stenting versus immediate stenting to prevent no- or slow-re ﬂ ow in acute ST-segment elevation myocardial infarction (DEFER-STEMI). J Am Coll Cardiol. 2014;63:2088 – 98 . [319] Kelbæk H, Høfsten DE, Køber L, Helqvist S, Kløvgaard L, Holmvang L, et al. Deferred versus conventional stent implantation in patients with ST-segment elevation myocardial infarction (DANAMI 3-DEFER): an open-label, randomised controlled trial. Lancet. 2016;387:2199 – 206 . [320] Engstrøm T, Kelbæk H, Helqvist S, Høfsten DE, Kløvgaard L, Holmvang L, 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 openlabel, randomised controlled trial. Lancet. 2015;386:665 – 71 . [321] Madsen JK, Grande P, Saunamäki K, Thayssen P, Kassis E, Eriksen U, et al. Danish multicenter randomized study of invasive versus conservative treatment in patients with inducible ischemia after thrombolysis in acute myocardial infarction (DANAMI). Circulation. 1997;96:748 – 55 . [322] Steg PG, Thuaire C, Himbert D, Carrié D, Champagne Sp, Coisne D, et al. DECOPI (DEsobstruction COronaire en Post-Infarctus): a randomized multi-centre trial of occluded artery angioplasty after acute myocardial infarction. Eur Heart J. 2004;25:2187 – 94 . [323] Pi Y, Roe MT, Holmes DN, Chiswell K, Garvey JL, Fonarow GC, et al. Utilization, characteristics, and in-hospital outcomes of coronary artery bypass grafting in patients with ST-segment-elevation myocardial infarction, 10. Circ Cardiovasc Qual Outcomes; 2017, e003490 . [324] Grothusen C, Friedrich C, Loehr J, Meinert J, Ohnewald E, Ulbricht U, 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 . [325] Stehli J, Duffy SJ, Koh Y, Martin C, Brennan A, Dinh DT, et al. Sex differences in radial access for percutaneous coronary intervention in acute coronary syndrome are independent of body size. Heart Lung Circ. 2021;30:108 – 14 . [326] Fazel R, Joseph TI, Sankardas MA, Pinto DS, Yeh RW, Kumbhani DJ, et al. Comparison of reperfusion strategies for ST-segment-elevation myocardial infarction: A multivariate network meta-analysis. J Am Heart Assoc. 2020;9:e015186 . [327] Borgia F, Goodman SG, Halvorsen S, Cantor WJ, Piscione F, Le May MR, et al. Early routine percutaneous coronary intervention after ﬁ brinolysis vs. standard therapy in ST-segment elevation myocardial infarction: a meta-analysis. Eur Heart J. 2010;31:2156 – 69 . [328] Madan M, Halvorsen S, Di Mario C, Tan M, Westerhout CM, Cantor WJ, et al. Relationship between time to invasive assessment and clinical outcomes of patients undergoing an early invasive strategy after ﬁ brinolysis for ST-segment elevation myocardial infarction: a patient-level analysis of the randomized early routine invasive clinical trials. JACC: Cardiovasc Imaging. 2015;8:166 – 74 . [329] Wijeysundera HC, Vijayaraghavan R, Nallamothu BK, Foody JM, Krumholz HM, Phillips CO, et al. Rescue angioplasty or repeat ﬁ brinolysis after failed ﬁ brinolytic therapy for ST-segment myocardial infarction: A meta-analysis of randomized trials. J Am Coll Cardiol. 2007;49:422 – 30 . [330] White HD. Systems of care: need for hub-and-spoke systems for both primary and systematic percutaneous coronary intervention after ﬁ brinolysis. Circulation. 2008;118:219 – 22 . [331] Gershlick AH, Stephens-Lloyd A, Hughes S, Abrams KR, Stevens SE, Uren NG, et al. Rescue angioplasty after failed thrombolytic therapy for acute myocardial infarction. N Engl J Med. 2005;353:2758 – 68 . [332] Aragam KG, Tamhane UU, Kline-Rogers E, Li J, Fox KA, Goodman SG, et al. Does simplicity compromise accuracy in ACS risk prediction? A retrospective analysis of the TIMI and GRACE risk scores. PLoS One. 2009;4:e7947 . [333] D ’ Ascenzo F, Biondi-Zoccai G, Moretti C, Bollati M, Omedè P, Sciuto F, et al. TIMI, GRACE and alternative risk scores in Acute Coronary Syndromes: a meta-analysis of 40 derivation studies on 216,552 patients and of 42 validation studies on 31,625 patients. Contemp Clin Trials. 2012;33:507 – 14 . [334] Bing R, Goodman SG, Yan AT, Fox K, Gale CP, Hyun K, et al. Use of clinical risk strati ﬁ cation in non-ST elevation acute coronary syndromes: an analysis from the CONCORDANCE registry. Eur Heart J Qual Care Clin Outcomes. 2018;4:309 – 17 . [335] Saar A, Marandi T, Ainla T, Fischer K, Blöndal M, Eha J. The risktreatment paradox in non-ST-elevation myocardial infarction patients according to their estimated GRACE risk. Int J Cardiol. 2018;272:26 – 32 . [336] Ranasinghe I, Alprandi-Costa B, Chow V, Elliott JM, Waites J, Counsell JT, et al. Risk strati ﬁ cation in the setting of non-ST elevation acute coronary syndromes 1999-2007. Am J Cardiol. 2011;108:617 – 24 . [337] Scott IA, Derhy PH, O ’ Kane D, Lindsay KA, Atherton JJ, Jones MA. Discordance between level of risk and intensity of evidence-based treatment in patients with acute coronary syndromes. Med J Aust. 2007;187:153 – 9 . [338] Chew DP, Hyun K, Morton E, Horsfall M, Hillis GS, Chow CK, et al. Objective risk assessment vs standard care for acute coronary syndromes: A randomized clinical trial. JAMA Cardiol. 2021;6:304 – 13 . [339] Gale CP, Stocken DD, Aktaa S, Reynolds C, Gilberts R, Brieger D, et al. Effectiveness of GRACE risk score in patients admitted to hospital with non-ST elevation acute coronary syndrome (UKGRIS): parallel group cluster randomised controlled trial. BMJ. 2023;381:e073843 . [340] Grinstein J, Bonaca MP, Jarolim P, Conrad MJ, Bohula-May E, Deenadayalu N, et al. Prognostic implications of low level cardiac troponin elevation using high-sensitivity cardiac troponin T. Clin Cardiol. 2015;38:230 – 5 . [341] Wang TKM, Mehta OH, Liao Y-WB, Wang MTM, Stewart R, White H. Meta-analysis of bleeding scores performance for acute coronary syndrome. Heart Lung Circ. 2020;29:1749 – 57 . [342] Urban P, Mehran R, Colleran R, Angiolillo DJ, Byrne RA, Capodanno D, et al. De ﬁ ning high bleeding risk in patients undergoing percutaneous coronary intervention. Circulation. 2019;140:240 – 61 . [343] Costa F, Van Klaveren D, Feres F, James S, Räber L, Pilgrim T, et al. Dual antiplatelet therapy duration based on ischemic and bleeding risks after coronary stenting. J Am Coll Cardiol. 2019;73:741 – 54 . [344] Wenzl FA, Kraler S, Ambler G, Weston C, Herzog SA, Räber L, et al. Sex-speci ﬁ c evaluation and redevelopment of the GRACE score in nonST-segment elevation acute coronary syndromes in populations from the UK and Switzerland: a multinational analysis with external cohort validation. Lancet. 2022;400:744 – 56 . [345] Hung J, Roos A, Kadesjö E, McAllister DA, Kimenai DM, Shah ASV, et al. Performance of the GRACE 2.0 score in patients with type 1 and type 2 myocardial infarction. Eur Heart J. 2021;42:2552 – 61 . [346] Subherwal S, Bach RG, Chen AY, Gage BF, Rao SV, Newby LK, et al. Baseline risk of major bleeding in non-ST-segment-elevation myocardial infarction: the CRUSADE (Can Rapid risk strati ﬁ cation of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA Guidelines) Bleeding Score. Circulation. 2009;119:1873 – 82 . [347] Chung K, Wilkinson C, Veerasamy M, Kunadian V. Frailty scores and their utility in older patients with cardiovascular disease. Interv Cardiol. 2021;16:e05 . [348] Damluji AA, Chung SE, Xue QL, Hasan RK, Walston JD, Forman DE, et al. Physical frailty phenotype and the development of geriatric syndromes in older adults with coronary heart disease. Am J Med. 2021;134:662 – 71 . [349] Ratcovich H, Beska B, Mills G, Holmvang L, Adams-Hall J, Stevenson H, et al. Five-year clinical outcomes in patients with frailty aged ${\geq}75$ years with non-ST elevation acute coronary syndrome undergoing invasive management. Eur Heart J Open. 2022;2:oeac035 . [350] Damluji AA, Huang J, Bandeen-Roche K, Forman DE, Gerstenblith G, Moscucci M, et al. Frailty among older adults with acute myocardial infarction and outcomes from percutaneous coronary interventions. J Am Heart Assoc. 2019;8:e013686 . [351] Alfredsson J, Clayton T, Damman P, Fox KA, Fredriksson M, Lagerqvist B, et al. Impact of an invasive strategy on 5 years outcome in men and women with non-ST-segment elevation acute coronary syndromes. Am Heart J. 2014;168:522 – 9 . [352] Damman P, Wallentin L, Fox KA, Windhausen F, Hirsch A, Clayton T, et al. Long-term cardiovascular mortality after procedure-related or spontaneous myocardial infarction in patients with non-ST-segment elevation acute coronary syndrome: a collaborative analysis of individual patient data from the FRISC II, ICTUS, and RITA-3 trials (FIR). Circulation. 2012;125:568 – 76 . [353] Fox KA, Clayton TC, Damman P, Pocock SJ, de Winter RJ, Tijssen JG, et al. Long-term outcome of a routine versus 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 – 45 . [354] Elgendy IY, Mahmoud AN, Wen X, Bavry AA. Meta-analysis of randomized trials of long-term all-cause mortality in patients with non STelevation acute coronary syndrome managed with routine invasive versus selective invasive strategies. Am J Cardiol. 2017;119:560 – 4 . [355] Elgendy IY, Kumbhani DJ, Mahmoud AN, Wen X, Bhatt DL, Bavry AA. Routine invasive versus selective invasive strategies for non STelevation acute coronary syndromes: an updated meta-analysis of randomized trials. Catheter Cardiovasc Interv. 2016;88:765 – 74 . [356] Hoenig MR, Aroney CN, Scott IA. Early invasive versus conservative strategies for unstable angina and non-ST elevation myocardial infarction in the stent era. Cochrane Database Syst Rev. 2010;3: CD004815 . [357] Lim SH, Anantharaman V, Sundram F, Chan ES-Y, Ang ES, Yo SL, et al. Stress myocardial perfusion imaging for the evaluation and triage of chest pain in the emergency department: a randomized controlled trial. J Nucl Cardiol. 2013;20:1002 – 12 . [358] Nabi F, Kassi M, Muhyieddeen K, Chang SM, Xu J, Peterson LE, et al. Optimizing evaluation of patients with low-to-intermediate-risk acute chest pain: a randomized study comparing stress myocardial perfusion tomography incorporating stress only imaging versus cardiac CT. J Nucl Cardiol. 2016;57:378 . [359] Siontis GCM, Mavridis D, Greenwood JP, Coles B, Nikolakopoulou A, Jüni P, et al. Outcomes of non-invasive diagnostic modalities for the detection of coronary artery disease: network meta-analysis of diagnostic randomised controlled trials. BMJ. 2018;360:k504 . [360] Smulders MW, Kietselaer BLJH, Wildberger JE, Dagnelie PC, Brunner – La Rocca H-P, Mingels AMA, et al. Initial imaging-guided strategy versus routine care in patients with non – ST-segment elevation myocardial infarction. J Am Coll Cardiol. 2019;74:2466 – 77 . [361] Linde JJ, Kelbæk H, Hansen TF, Sigvardsen PE, Torp-Pedersen C, Bech J, et al. Coronary CT angiography in patients with non-ST-segment elevation acute coronary syndrome. J Am Coll Cardiol. 2020;75:453 – 63 . [362] Dedic A, Lubbers MM, Schaap J, Lammers J, Lamfers EJ, Rensing BJ, et al. Coronary CT angiography for suspected ACS in the era of highsensitivity troponins: randomized multicenter study. J Am Coll Cardiol. 2016;67:16 – 26 . [363] Mehta SR, Granger CB, Boden WE, Steg PG, Bassand J-P, Faxon DP, et al. Early versus delayed invasive intervention in acute coronary syndromes. N Engl J Med. 2009;360:2165 – 75 . [364] Kofoed KF, Kelbæk H, Hansen PR, Torp-Pedersen C, Høfsten D, Kløvgaard L, et al. Early versus standard care invasive examination and treatment of patients with non-ST-segment elevation acute coronary syndrome. Circulation. 2018;138:2741 – 50 . [365] Kite TA, Kurmani SA, Bountziouka V, Cooper NJ, Lock ST, Gale CP, 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 – 61 . [366] Jobs A, Mehta SR, Montalescot G, Vicaut E, Van ’ t Hof AWJ, Badings EA, et al. Optimal timing of an invasive strategy in patients with non-STelevation acute coronary syndrome: a meta-analysis of randomised trials. Lancet. 2017;390:737 – 46 . [367] Stone GW, Christiansen EH, Ali ZA, Andreasen LN, Maehara A, Ahmad Y, et al. Intravascular imaging-guided coronary drug-eluting stent implantation: an updated network meta-analysis. Lancet. 2024;403:824 – 37 . [368] Kuno T, Kiyohara Y, Maehara A, Ueyama HA, Kampaktsis PN, Takagi H, et al. Comparison of Intravascular Imaging, Functional, or Angiographically Guided Coronary Intervention. J Am Coll Cardiol. 2023;82:2167 – 76 . [369] Tegn N, Abdelnoor M, Aaberge L, Endresen K, Smith P, Aakhus S, et al. Invasive versus conservative strategy in patients aged 80 years or older with non-ST-elevation myocardial infarction or unstable angina pectoris (After Eighty study): an open-label randomised controlled trial. Lancet. 2016;387:1057 – 65 . [370] Savonitto S, Cavallini C, Petronio AS, Murena E, Antonicelli R, Sacco A, et al. Early aggressive versus initially conservative treatment in elderly patients with non-ST-segment elevation acute coronary syndrome: a randomized controlled trial. JACC: Cardiovasc Imaging. 2012;5:906 – 16 . [371] Sanchis J, Núñez E, Barrabés JA, Marín F, Consuegra-Sánchez L, Ventura S, et al. Randomized comparison between the invasive and conservative strategies in comorbid elderly patients with non-ST elevation myocardial infarction. Eur J Intern Med. 2016;35:89 – 94 . [372] de Belder A, Myat A, Blaxill J, Haworth P, O ’ Kane PD, Hatrick R, et al. Revascularisation or medical therapy in elderly patients with acute anginal syndromes: the RINCAL randomised trial. EuroIntervention. 2021;17:67 – 74 . [373] Hirlekar G, Libungan B, Karlsson T, Bäck M, Herlitz J, Albertsson P. Percutaneous coronary intervention in the very elderly with NSTE-ACS: the randomized $^{80+}$ study. Scand Cardiovasc J. 2020;54:315 – 21 . [374] Mills GB, Ratcovich H, Adams-Hall J, Beska B, Kirkup E, Raharjo DE, et al. Is the contemporary care of the older persons with acute coronary syndrome evidence-based? Eur Heart J Open. 2022;2:oeab044 . [375] Biscaglia S, Guiducci V, Escaned J, Moreno R, Lanzilotti V, Santarelli A, et al. Complete or culprit-only PCI in older patients with myocardial infarction. N Engl J Med. 2023;389:889 – 98 . [376] Kaura A, Sterne J, Trickey A, Abbott S, Mulla A, Glampson B, et al. Invasive versus non-invasive management of older patients with non-ST elevation myocardial infarction (SENIOR-NSTEMI): a cohort study based on routine clinical data. Lancet. 2020;396:623 – 34 . [377] Gnanenthiran SR, Kritharides L, D ’ Souza M, Lowe HC, Brieger DB. Revascularisation compared with initial medical therapy for non-STelevation acute coronary syndromes in the elderly: a meta-analysis. Heart. 2017;103:1962 – 9 . [378] Ma W, Liang Y, Zhu J. Early invasive versus initially conservative strategy in elderly patients older than 75 years with non-ST-elevation acute coronary syndrome: A meta-analysis. Heart Lung Circ. 2018;27:611 – 20 . [379] Sanchis J, Bueno H, Miñana G, Guerrero C, Martí D, Martínez-Sellés M, et al. Effect of routine invasive vs conservative strategy in older adults with frailty and non – ST-segment elevation acute myocardial infarction: a randomized clinical trial. JAMA Intern Med. 407 – 415. [380] Lopez D, Katzenellenbogen JM, San ﬁ lippo FM, Woods JA, Hobbs MS, Knuiman MW, et al. Transfers to metropolitan hospitals and coronary angiography for rural Aboriginal and non-Aboriginal patients with acute ischaemic heart disease in Western Australia. BMC Cardiovasc Disord. 2014;14:58 . [381] ISIS-2 (Second International Study of Infarct Survival) Collaborative group. Randmomised trial of intravenous strektokinase, oral, aspirin, both, or neither among 17,187 cases of syspected acute myocardial infarctionL ISIS-2. Lancet. 1988;2:349 – 60 . [382] Mehta SR, Bassand JP, Chrolavicius S, Diaz R, Eikelboom JW, Fox KA, et al. Dose comparisons of clopidogrel and aspirin in acute coronary syndromes. N Engl J Med. 2010;363:930 – 42 . [383] Chen ZM, Jiang LX, Chen YP, Xie JX, Pan HC, Peto R, et al. Addition of clopidogrel to aspirin in 45,852 patients with acute myocardial infarction: randomised placebo-controlled trial. Lancet. 2005;366:1607 – 21 . [384] Sabatine MS, Cannon CP, Gibson CM, López-Sendón JL, Montalescot G, Theroux P, et al. Addition of clopidogrel to aspirin and ﬁ brinolytic therapy for myocardial infarction with ST-segment elevation. N Engl J Med. 2005;352:1179 – 89 . [385] Hamilos M, Kanakakis J, Anastasiou I, Karvounis C, Vasilikos V, Goudevenos J, et al. Ticagrelor versus clopidogrel in patients with STEMI treated with thrombolysis: the MIRTOS trial. EuroIntervention. 2021;16:1163 – 9 . [386] Berwanger O, Nicolau JC, Carvalho AC, Jiang L, Goodman SG, Nicholls SJ, et al. Ticagrelor vs Clopidogrel after ﬁ brinolytic therapy in patients with ST-elevation myocardial infarction: a randomized clinical trial. JAMA Cardiol. 2018;3:391 – 9 . [387] Wiviott SD, Braunwald E, McCabe CH, Montalescot G, Ruzyllo W, Gottlieb S, et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2007;357:2001 – 15 . [388] Wallentin L, Becker RC, Budaj A, Cannon CP, Emanuelsson H, Held C, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009;361:1045 – 57 . [389] Gewehr DM, Carvalho PEdP, Dagostin CS, Cardoso R, Kubrusly TBL, Kubrusly FB, et al. Pretreatment with P2Y12 inhibitors in ST-elevation myocardial infarction: A systematic review and meta-analysis. Catheter Cardiovasc Interv. 2023;102:200 – 11 . [390] Yusuf S, Zhao F, Mehta SR, Chrolavicius S, Tognoni G, Fox KK, 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 . [391] Montalescot G, Bolognese L, Dudek D, Goldstein P, Hamm C, Tanguay JF, et al. Pretreatment with prasugrel in non-ST-segment elevation acute coronary syndromes. N Engl J Med. 2013;369:999 – 1010 . [392] Dworeck C, Redfors B, Angerås O, Haraldsson I, Odenstedt J, Ioanes D, et al. Association of pretreatment with P2Y12 receptor antagonists preceding percutaneous coronary intervention in non-ST-segment elevation acute coronary syndromes with outcomes. JAMA Netw Open. 2020;3: e2018735 . [393] Roe MT, Armstrong PW, Fox KAA, White HD, Prabhakaran D, Goodman SG, et al. Prasugrel versus clopidogrel for acute coronary syndromes without revascularization. N Engl J Med. 2012;367:1297 – 309 . [394] Schüpke S, Neumann F-J, Menichelli M, Mayer K, Bernlochner I, Wöhrle J, et al. Ticagrelor or prasugrel in patients with acute coronary syndromes. N Engl J Med. 2019;381:1524 – 34 . [395] Kubica J, Jaguszewski M. ISAR-REACT 5 - What have we learned? Cardiol J. 2019;26:427 – 8 . [396] Claassens DMF, Vos GJA, Bergmeijer TO, Hermanides RS, van ’ t Hof AWJ, van der Harst P, et al. A genotype-guided strategy for oral P2Y12 inhibitors in primary PCI. N Engl J Med. 2019;381:1621 – 31 . [397] Sibbing D, Aradi D, Jacobshagen C, Gross L, Trenk D, Geisler T, et al. Guided de-escalation of antiplatelet treatment in patients with acute coronary syndrome undergoing percutaneous coronary intervention (TROPICAL-ACS): a randomised, open-label, multicentre trial. Lancet. 2017;390:1747 – 57 . [398] Pereira NL, Farkouh ME, So D, Lennon R, Geller N, Mathew V, et al. Effect of genotype-guided oral P2Y12 inhibitor selection vs conventional clopidogrel therapy on ischemic outcomes after percutaneous coronary intervention: the TAILOR-PCI randomized clinical trial. JAMA. 2020;324:761 – 71 . [399] O ’ Donoghue ML, Marston NA. Time for a paradigm shift? Making the case for tailored selection of antiplatelet therapy. Eur Heart J. 2022;43:968 – 70 . [400] Galli M, Benenati S, Franchi F, Rollini F, Capodanno D, Biondi-Zoccai G, et al. Comparative effects of guided vs. potent P2Y12 inhibitor therapy in acute coronary syndrome: a network meta-analysis of 61 898 patients from 15 randomized trials. Eur Heart J. 2022;43:959 – 67 . [401] Kim CJ, Park M-W, Kim MC, Choo E-H, Hwang B-H, Lee KY, et al. Unguided de-escalation from ticagrelor to clopidogrel in stabilised patients with acute myocardial infarction undergoing percutaneous coronary intervention (TALOS-AMI): an investigator-initiated, open-label, multicentre, non-inferiority, randomised trial. Lancet. 2021;398:1305 – 16 . [402] Kim H-S, Kang J, Hwang D, Han J-K, Yang H-M, Kang H-J, et al. Prasugrel-based de-escalation of dual antiplatelet therapy after percutaneous coronary intervention in patients with acute coronary syndrome (HOST-REDUCE-POLYTECH-ACS): an open-label, multicentre, noninferiority randomised trial. Lancet. 2020;396:1079 – 89 . [403] Cuisset T, Deharo P, Quilici J, Johnson TW, Deffarges S, Bassez C, et al. Bene ﬁ t of switching dual antiplatelet therapy after acute coronary syndrome: the TOPIC (timing of platelet inhibition after acute coronary syndrome) randomized study. Eur Heart J. 2017;38:3070 – 8 . [404] Jeong Y-H. “ East asian paradox ” : Challenge for the current antiplatelet strategy of “ one-guideline- ﬁ ts-all races ” in acute coronary syndrome. Curr Cardiol Rep. 2014;16:485 . [405] Cannon CP, Bhatt DL, Oldgren J, Lip GYH, Ellis SG, Kimura T, et al. Dual antithrombotic therapy with dabigatran after PCI in atrial ﬁ brillation. N Engl J Med. 2017;377:1513 – 24 . [406] Gibson CM, Mehran R, Bode C, Halperin J, Verheugt FW, Wildgoose P, et al. Prevention of bleeding in patients with atrial ﬁ brillation undergoing PCI. N Engl J Med. 2016;375:2423 – 34 . [407] Lopes RD, Heizer G, Aronson R, Vora AN, Massaro T, Mehran R, et al. Antithrombotic therapy after acute coronary syndrome or PCI in atrial ﬁ brillation. N Engl J Med. 2019;380:1509 – 24 . [408] Park DY, Wang P, An S, Grimshaw AA, Frampton J, Ohman EM, et al. Shortening the duration of dual antiplatelet therapy after percutaneous coronary intervention for acute coronary syndrome: a systematic review and meta-analysis. Am Heart J. 2022;251:101 – 14 . [409] ten Berg JM, van ’ t Hof AW, Dill T, Heestermans T, van Werkum JW, Mosterd A, et al. Effect of early, pre-hospital initiation of high bolus dose tiro ﬁ ban in patients with ST-segment elevation myocardial infarction on short- and long-term clinical outcome. J Am Coll Cardiol. 2010;55:2446 – 55 . [410] Ellis SG, Tendera M, de Belder MA, van Boven AJ, Widimsky P, Janssens L, et al. Facilitated PCI in patients with ST-elevation myocardial infarction. N Engl J Med. 2008;358:2205 – 17 . [411] Akpek M, Sahin O, Sarli B, Baktir AO, Saglam H, Urkmez S, et al. Acute effects of intracoronary tiro ﬁ ban on no-re ﬂ ow phenomena in patients with st-segment elevated myocardial infarction undergoing primary percutaneous coronary intervention. Angiology. 2014;66:560 – 7 . [412] Friedland S, Eisenberg MJ, Shimony A. Meta-analysis of randomized controlled trials of intracoronary versus intravenous administration of glycoprotein IIb/IIIa inhibitors during percutaneous coronary intervention for acute coronary syndrome. Am J Cardiol. 2011;108:1244 – 51 . [413] Tricoci P, Newby LK, Hasselblad V, Kong DF, Giugliano RP, White HD, et al. Upstream use of small-molecule glycoprotein iib/iiia inhibitors in patients with non-ST-segment elevation acute coronary syndromes: a systematic overview of randomized clinical trials, 4. Circ Cardiovasc Qual Outcomes; 2011;. p. 448 – 58 . [414] Giugliano RP, White JA, Bode C, Armstrong PW, Montalescot G, Lewis BS, et al. Early versus delayed, provisional Epti ﬁ batide in acute coronary syndromes. N Engl J Med. 2009;360:2176 – 90 . [415] Rof ﬁ M, Chew DP, Mukherjee D, Bhatt DL, White JA, Moliterno DJ, et al. Platelet glycoprotein IIb/IIIa inhibition in acute coronary syndromes. Gradient of bene ﬁ t related to the revascularization strategy. Eur Heart J. 2002;23:1441 – 8 . [416] Rossini R, Iorio A, Pozzi R, Bianco M, Musumeci G, Leonardi S, et al. Aspirin desensitization in patients with coronary artery disease. Circ Cardiovasc Interv. 2017;10:e004368 . [417] Dyke CM, Bhatia D, Lorenz TJ, Marso SP, Tardiff BE, Hogeboom C, et al. Immediate coronary artery bypass surgery after platelet inhibition with epti ﬁ batide: results from PURSUIT. Ann Thor Surg. 2000;70:866 – 71 . [418] Bizzarri F, Scolletta S, Tucci E, Lucidi M, Davoli G, Toscano T, et al. Perioperative use of tiro ﬁ ban hydrochloride (Aggrastat) does not increase surgical bleeding after emergency or urgent coronary artery bypass grafting. J Thorac Cardiovasc Surg. 2001;122:1181 – 5 . [419] Lincoff AM, LeNarz LA, Despotis GJ, Smith PK, Booth JE, Raymond RE, et al. Abciximab and bleeding during coronary surgery: results from the EPILOG and EPISTENT trials. Ann Thor Surg. 2000;70:516 – 26 . [420] GUSTO investigators. An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. N Engl J Med. 1993;329:673 – 82 . [421] Assessment of the Safety and Ef ﬁ cacy of a New Thrombolytic Regimen (ASSENT)-3 Investigators. Ef ﬁ cacy and safety of tenecteplase in combination with enoxaparin, abciximab, or unfractionated heparin: the ASSENT-3 randomised trial in acute myocardial infarction. Lancet. 2001;358:605 – 13 . [422] Cavender MA, Sabatine MS. Bivalirudin versus heparin in patients planned for percutaneous coronary intervention: a meta-analysis of randomised controlled trials. Lancet. 2014;384:599 – 606 . [423] Capodanno D, Gargiulo G, Capranzano P, Mehran R, Tamburino C, Stone GW. Bivalirudin versus heparin with or without glycoprotein IIb/ IIIa inhibitors in patients with STEMI undergoing primary PCI: an updated meta-analysis of 10,350 patients from ﬁ ve randomized clinical trials. Eur Heart J Acute Cardiovasc Care. 2016;5:253 – 62 . [424] Li Y, Liang Z, Qin L, Wang M, Wang X, Zhang H, et al. Bivalirudin plus a high-dose infusion versus heparin monotherapy in patients with STsegment elevation myocardial infarction undergoing primary percutaneous coronary intervention: a randomised trial. Lancet. 2022;400: 1847 – 57 . [425] The RISC Group. Risk of myocardial infarction and death during treatment with low dose aspirin and intravenous heparin in men with unstable coronary artery disease. Lancet. 1990;336:827 – 30 . [426] Telford AM, Wilson C. Trial of heparin versus atenolol in prevention of myocardial infarction in intermediate coronary syndrome. Lancet. 1981;1:1225 – 8 . [427] Théroux P, Ouimet H, McCans J, Latour JG, Joly P, Lévy G, et al. Aspirin, heparin, or both to treat acute unstable angina. N Engl J Med. 1988;319:1105 – 11 . [428] Galli M, Andreotti F, D ’ Amario D, Vergallo R, Vescovo GM, Giraldi L, et al. Antithrombotic therapy in the early phase of non-ST-elevation acute coronary syndromes: a systematic review and meta-analysis. Eur Heart J Cardiovasc Pharmacother. 2019;6:43 – 56 . [429] SYNERGY Trial Investigators. Enoxaparin vs unfractionated heparin in high-risk patients with non – ST-segment elevation acute coronary syndromes managed with an intended early invasive strategy primary results of the SYNERGY randomized trial. JAMA. 2004;292:45 – 54 . [430] Nührenberg TG, Hochholzer W, Mashayekhi K, Ferenc M, Neumann FJ. Ef ﬁ cacy and safety of bivalirudin for percutaneous coronary intervention in acute coronary syndromes: a meta-analysis of randomizedcontrolled trials. Clin Res Cardiol. 2018;107:807 – 15 . [431] Yusuf S, Mehta SR, Chrolavicius S, Afzal R, Pogue J, Granger CB, et al. Comparison of fondaparinux and enoxaparin in acute coronary syndromes. N Engl J Med. 2006;354:1464 – 76 . [432] Antman EM, Morrow DA, McCabe CH, Murphy SA, Ruda M, Sadowski $Z,$ et al. Enoxaparin versus unfractionated heparin with ﬁ brinolysis for ST-elevation myocardial infarction. N Engl J Med. 2006;354:1477 – 88 . [433] Fox KAA, Antman EM, Montalescot G, Agewall S, SomaRaju B, Verheugt FWA, et al. The impact of renal dysfunction on outcomes in the ExTRACT-TIMI 25 trial. J Am Coll Cardiol. 2007;49:2249 – 55 . [434] Fahrni G, Wolfrum M, De Maria GL, Banning AP, Benedetto U, Kharbanda RK. Prolonged high-dose bivalirudin infusion reduces major bleeding without increasing stent thrombosis in patients undergoing primary percutaneous coronary intervention: Novel insights from an updated meta-analysis. J Am Heart Assoc. e003515. [435] Brieger D, Solanki V, Gaynor M, Booth V, MacDonald R, Freedman SB. Optimal strategy for administering enoxaparin to patients undergoing coronary angiography without angioplasty for acute coronary syndromes. Am J Cardiol. 2002;89:1167 – 70 . [436] Angiolillo DJ, Bhatt DL, Cannon CP, Eikelboom JW, Gibson CM, Goodman SG, et al. Antithrombotic therapy in patients with atrial ﬁ brillation treated with oral anticoagulation undergoing percutaneous coronary intervention: a North American perspective: 2021 update. Circulation. 2021;143:583 – 96 . [437] Karam N, Bataille S, Marijon E, Taf ﬂ et M, Benamer H, Caussin C, et al. Incidence, mortality, and outcome-predictors of sudden cardiac arrest complicating myocardial infarction prior to hospital admission. Circ Cardiovasc Genet. 2019;12:e007081 . [438] Garot P, Lefevre T, Eltchaninoff H, Morice M-C, Tamion F, Abry B, et al. Six-month outcome of emergency percutaneous coronary intervention in resuscitated patients after cardiac arrest complicating ST-elevation myocardial infarction. Circulation. 2007;115:1354 – 62 . [439] Kern KB, Rahman O. Emergent percutaneous coronary intervention for resuscitated victims of out-of-hospital cardiac arrest. Catheter Cardiovasc Interv. 2010;75:616 – 24 . [440] Dumas F, Cariou A, Manzo-Silberman S, Grimaldi D, Vivien B, Rosencher J, et al. Immediate percutaneous coronary intervention is associated with better survival after out-of-hospital cardiac arrest. Circ Cardiovasc Genet. 2010;3:200 – 7 . [441] Hamed M, Neupane G, Abdelsalam M, Elkhawas I, Morsy M, Khalili H, et al. Meta-analysis on early versus delayed coronary angiography for patients with out-of-hospital cardiac arrest without ST-elevation myocardial infarction. Am J Cardiol. 2023;188:41 – 3 . [442] Böttiger BW, Arntz H-R, Chamberlain DA, Bluhmki E, Belmans A, Danays T, et al. Thrombolysis during resuscitation for out-of-hospital cardiac arrest. N Engl J Med. 2008;359:2651 – 62 . [443] Hirt LS, Kandan SR, Rahbi H, Dastidar A, Khawaja MZ, Mozid A, et al. Three factors combined predict futility of emergency coronary angiography after out-of-hospital cardiac arrest. J Am Coll Cardiol. 2018;72:1753 – 5 . [444] Thiele H, Akin I, Sandri M, Fuernau G, de Waha S, Meyer-Saraei R, et al. PCI strategies in patients with acute myocardial infarction and cardiogenic shock. N Engl J Med. 2017;377:2419 – 32 . [445] Thiele H, Akin I, Sandri M, de Waha-Thiele S, Meyer-Saraei R, Fuernau G, et al. One-year outcomes after PCI strategies in cardiogenic shock. N Engl J Med. 2018;379:1699 – 710 . [446] Kolte D, Sardar P, Khera S, Zeymer U, Thiele H, Hochadel M, et al. Culprit vessel-only versus multivessel percutaneous coronary intervention in patients with cardiogenic shock complicating ST-segment – elevation myocardial infarction. Circ Cardiovasc Genet. 2017;10: e005582 . [447] Thiele H, Zeymer U, Neumann F-J, Ferenc M, Olbrich H-G, Hausleiter J, et al. Intraaortic balloon support for myocardial infarction with cardiogenic shock. N Engl J Med. 2012;367:1287 – 96 . [448] Patel MR, Smalling RW, Thiele H, Barnhart HX, Zhou Y, Chandra P, et al. Intra-aortic balloon counterpulsation and infarct size in patients with acute anterior myocardial infarction without shock: the CRISP AMI randomized trial. JAMA. 2011;306:1329 – 37 . [449] Sjauw KD, Engström AE, Vis MM, van der Schaaf RJ, Baan J Jr, Koch KT, et al. A systematic review and meta-analysis of intra-aortic balloon pump therapy in ST-elevation myocardial infarction: should we change the guidelines? Eur Heart J. 2009;30:459 – 68 . [450] Thiele H, Zeymer U, Akin I, Behnes M, Rassaf T, Mahabadi AA, et al. Extracorporeal life support in infarct-related cardiogenic shock. N Engl J Med. 2023;389:1286 – 97 . [451] Zeymer U, Freund A, Hochadel M, Ostadal P, Belohlavek J, Rokyta R, et al. Venoarterial extracorporeal membrane oxygenation in patients with infarct-related cardiogenic shock: an individual patient data metaanalysis of randomised trials. Lancet. 1338 – 1346. [452] Møller JE, Engstrøm T, Jensen LO, Eiskjær H, Mangner N, Polzin A, et al. Microaxial ﬂ ow pump or standard care in infarct-related cardiogenic shock. N Engl J Med. 2024;390:1382 – 93 . [453] Vallabhajosyula S, Verghese D, Bell MR, Murphree DH, Cheungpasitporn W, Miller PE, et al. Fibrinolysis vs. primary percutaneous coronary intervention for ST-segment elevation myocardial infarction cardiogenic shock. ESC Heart Fail. 2021;8:2025 – 35 . [454] Politi L, Sgura F, Rossi R, Monopoli D, Guerri E, Leuzzi C, 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 . [455] Gershlick AH, Khan JN, Kelly DJ, Greenwood JP, Sasikaran T, Curzen N, 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 – 72 . [456] Mehta SR, Wood DA, Storey RF, Mehran R, Bainey KR, Nguyen H, et al. Complete revascularization with multivessel PCI for myocardial infarction. N Engl J Med. 2019;381:1411 – 21 . [457] Dambrink J-HE, Debrauwere JP, van ’ t Hof AWJ, Ottervanger J-P, Gosselink ATM, Hoorntje JCA, et al. Non-culprit lesions detected during primary PCI: treat invasively or follow the guidelines? EuroIntervention. 2010;5:968 – 75 . [458] Carlo DM, Mara S, Flavio A, Imad S, Antonio M, Anna P, et al. Single vs multivessel treatment during primary angioplasty: results of the multicentre randomised HEpacoat TM for cuLPrit or multivessel stenting for Acute Myocardial Infarction (HELP AMI) Study. Int J Cardiovasc Intervent. 2004;6:128 – 33 . [459] Hamza M, Mahmoud AN, Elgendy IY. A randomized trial of complete versus culprit-only revascularization during primary percutaneous coronary intervention in diabetic patients with acute ST elevation myocardial infarction and multi vessel disease. J Interv Cardiol. 2016;29:241 – 7 . [460] Høfsten DE, Kelbæk H, Helqvist S, Kløvgaard L, Holmvang L, Clemmensen P, et al. The third DANish study of optimal acute treatment of patients with ST-segment elevation myocardial infarction: ischemic postconditioning or deferred stent implantation versus conventional primary angioplasty and complete revascularization versus treatment of culprit lesion only: rationale and design of the DANAMI 3 trial program. Am Heart J. 2015;169:613 – 21 . [461] Damian JK, Gerald PM, Daniel JB, Nicholas PC, Miles D, John PG, et al. Complete Versus culprit-Lesion only PRimary PCI Trial (CVLPRIT): a multicentre trial testing management strategies when multivessel disease is detected at the time of primary PCI: rationale and design. EuroIntervention. 2013;8:1190 – 8 . [462] McCann GP, Khan JN, Greenwood JP, Nazir S, Dalby M, Curzen N, et al. Complete versus lesion-only primary PCI: the randomized cardiovascular MR CvLPRIT substudy. J Am Coll Cardiol. 2015;66:2713 – 24 . [463] Sadjadieh G, Engstrøm T, Helqvist S, Hofsten DE, Køber L, Pedersen F, et al. Bleeding episodes in “ complete, staged ” versus “ culprit only ” revascularisation in patients with multivessel disease and ST-segment elevation myocardial infarction: a DANAMI-3-PRIMULTI substudy. EuroIntervention. 2016;12:1231 – 8 . [464] Smits PC, Abdel-Wahab M, Neumann F-J, Boxma-de Klerk BM, Lunde K, Schotborgh CE, et al. Fractional ﬂ ow reserve – guided multivessel angioplasty in myocardial infarction. N Engl J Med. 2017;376:1234 – 44 . [465] Wald DS, Morris JK, Wald NJ, Chase AJ, Edwards RJ, Hughes LO, et al. Randomized trial of preventive angioplasty in myocardial infarction. N Engl J Med. 2013;369:1115 – 23 . [466] Manoharan G, Belardi JA, Du Z, Lee MS, Qiao S, Serruys PW, et al. Comparison of clinical outcomes after multivessel versus single-vessel stenting with the zotarolimus-eluting stent in the RESOLUTE Global Clinical Trial Program. EuroIntervention. 2017;12:1605 – 13 . [467] Bainey KR, Engstrøm T, Smits PC, Gershlick AH, James SK, Storey RF, et al. Complete vs culprit-lesion-only revascularization for ST-segment elevation myocardial infarction: A systematic review and meta-analysis. JAMA Cardiol. 2020;5:881 – 8 . [468] Stähli BE, Varbella F, Linke A, Schwarz B, Felix SB, Seiffert M, et al. Timing of complete revascularization with multivessel pci for myocardial infarction. N Engl J Med. 2023;389:1368 – 79 . [469] Siebert VR, Borgaonkar S, Jia X, Nguyen HL, Birnbaum Y, Lakkis NM, et al. Meta-analysis comparing multivessel versus culprit coronary arterial revascularization for patients with non-ST-segment elevation acute coronary syndromes. Am J Cardiol. 2019;124:1501 – 11 . [470] Elbadawi A, Dang AT, Hamed M, Eid M, Prakash Hiriyur Prakash M, Saleh M, et al. FFR- versus angiography-guided revascularization for nonculprit stenosis in STEMI and multivessel disease: a network metaanalysis. JACC: Cardiovasc Imaging. 2022;15:656 – 66 . [471] Archilletti F, Ricci F, Pelliccia F, Dangas G, Giuliani L, Radico F, et al. Coronary angiography- or fractional ﬂ ow reserve-guided complete revascularization in multivessel disease STEMI: A Bayesian hierarchical network meta-analysis. Int J Cardiol. 2023;370:122 – 8 . [472] Layland J, Oldroyd KG, Curzen N, Sood A, Balachandran K, Das R, et al. Fractional ﬂ ow reserve vs. angiography in guiding management to optimize outcomes in non-ST-segment elevation myocardial infarction: the British Heart Foundation FAMOUS – NSTEMI randomized trial. Eur Heart J. 2015;36:100 – 11 . [473] Ntalianis A, Sels J-W, Davidavicius G, Tanaka N, Muller O, Trana C, et al. Fractional ﬂ ow reserve for the assessment of nonculprit coronary artery stenoses in patients with acute myocardial infarction. JACC: Cardiovasc Interv. 2010;3:1274 – 81 . [474] Puymirat E, Cayla G, Simon T, Steg PG, Montalescot G, DurandZaleski I, et al. Multivessel PCI guided by FFR or angiography for myocardial infarction. N Engl J Med. 2021;385:297 – 308 . [475] Lee JM, Kim HK, Park KH, Choo EH, Kim CJ, Lee SH, et al. Fractional ﬂ ow reserve versus angiography-guided strategy in acute myocardial infarction with multivessel disease: a randomized trial. Eur Heart J. 2022;44:473 – 84 . [476] Yousef S, Sultan I, VonVille HM, Kahru K, Arnaoutakis GJ. Surgical management for mechanical complications of acute myocardial infarction: a systematic review of long-term outcomes. Ann Cardiothorac Surg. 2022;11:239 – 51 . [477] Chevalier P, Burri H, Fahrat F, Cucherat M, Jegaden O, Obadia J-F, et al. Perioperative outcome and long-term survival of surgery for acute post-infarction mitral regurgitation. Eur J Cardiothorac Surg. 2004;26:330 – 5 . [478] Kirov H, Caldonazo T, Rahouma M, Robinson NB, Demetres M, Serruys PW, et al. A systematic review and meta-analysis of percutaneous coronary intervention compared to coronary artery bypass grafting in non-ST-elevation acute coronary syndrome. Sci Rep. 2022;12:5138 . [479] Hadaya J, Sanaiha Y, Tran Z, Downey P, Shemin RJ, Benharash P. Timing of coronary artery bypass grafting in acute coronary syndrome: a national analysis. Ann Thor Surg. 2022;113:1482 – 90 . [480] Hayes SN, Kim ESH, Saw J, Adlam D, Arslanian-Engoren C, Economy KE, et al. Spontaneous coronary artery dissection: current state of the science: a scienti ﬁ c statement from the American Heart Association. Circulation. 2018;137:e523 – 57 . [481] Fahey JK, Chew A, Ihdayhid AR, Rashid HN, Zaman S, Nicholls SJ, et al. Women with spontaneous coronary artery dissection are at increased risk of iatrogenic coronary artery dissection. Heart Lung Circ. 2020;30(1):e23 – 8 . [482] Hassan S, Samuel R, Starovoytov A, Lee C, Aymong E, Saw J. Outcomes of percutaneous coronary intervention in patients with spontaneous coronary artery dissection, 2021. J Interv Cardiol; 2021, 6686230 . [483] Kotecha D, Garcia-Guimaraes M, Premawardhana D, Pellegrini D, Oliver-Williams C, Bountziouka V, et al. Risks and bene ﬁ ts of percutaneous coronary intervention in spontaneous coronary artery dissection. Heart. 2021;107:1398 . [484] Tweet MS, Eleid MF, Best PJM, Lennon RJ, Lerman A, Rihal CS, et al. Spontaneous coronary artery dissection. Circ Cardiovasc Interv. 2014;7:777 – 86 . [485] Martins JL, Afreixo V, Santos L, Costa M, Santos J, Gonçalves L. Medical treatment or revascularisation as the best approach for spontaneous coronary artery dissection: A systematic review and meta-analysis. Eur Heart J Acute Cardiovasc Care. 2018;7:614 – 23 . [486] Lobo AS, Cantu SM, Sharkey SW, Grey EZ, Storey K, Witt D, et al. Revascularization in patients with spontaneous coronary artery dissection and ST-segment elevation myocardial infarction. J Am Coll Cardiol. 2019;74:1290 – 300 . [487] Jamil A, Tajrishi FZ, Kahe F, Naja ﬁ H, Montazerin SM, Shojaei F, et al. Spontaneous coronary artery dissection managed with a conservative or revascularization approach: a meta-analysis. J Cardiovasc Med. 2020;21:42 – 50 . [488] Reynolds HR, Maehara A, Kwong RY, Sedlak T, Saw J, Smilowitz NR, et al. Coronary optical coherence tomography and cardiac magnetic resonance imaging to determine underlying causes of myocardial infarction with nonobstructive coronary arteries in women. Circulation. 2021;143:624 – 40 . [489] White K, Kinarivala M, Scott I. Diagnostic features, management and prognosis of type 2 myocardial infarction compared to type 1 myocardial infarction: a systematic review and meta-analysis. BMJ Open. 2022;12:e055755 . [490] Atherton JJ, Sindone A, De Pasquale CG, Driscoll A, MacDonald PS, Hopper I, et al. National Heart Foundation of Australia and Cardiac Society of Australia and New Zealand: guidelines for the prevention, detection, and management of heart failure in Australia 2018. Heart Lung Circ. 2018;27:1123 – 208 . [491] Sandau KE, Funk M, Auerbach A, Barsness GW, Blum K, Cvach M, et al. Update to practice standards for electrocardiographic monitoring in hospital settings: a scienti ﬁ c statement from the American Heart Association. Circulation. 2017;136:e273 – 344 . [492] Shue McGuf ﬁ n K, Ortiz S. Daily electrocardiogram electrode change and the effect on frequency of nuisance alarms. Dimens Crit Care Nurs. 2019;38:187 – 91 . [493] Walsh-Irwin C, Jurgens CY. Proper skin preparation and electrode placement decreases alarms on a telemetry unit. Dimens Crit Care Nurs. 2015;34:134 – 9 . [494] Dibben GO, Faulkner J, Oldridge N, Rees K, Thompson DR, Zwisler AD, et al. Exercise-based cardiac rehabilitation for coronary heart disease: a meta-analysis. Eur Heart J. 2023;44:452 – 69 . [495] McDonagh STJ, Dalal H, Moore S, Clark CE, Dean SG, Jolly K, et al. Home-based versus centre-based cardiac rehabilitation. Cochrane Database Syst Rev. 2023;10:CD007130 . [496] Chow CK, Jolly S, Rao-Melacini P, Fox KA, Anand SS, Yusuf S. Association of diet, exercise, and smoking modi ﬁ cation with risk of early cardiovascular events after acute coronary syndromes. Circulation. 2010;121:750 – 8 . [497] Wu AD, Lindson N, Hartmann-Boyce J, Wahedi A, Hajizadeh A, Theodoulou A, et al. Smoking cessation for secondary prevention of cardiovascular disease. Cochrane Database Syst Rev. CD014936. [498] Yudi MB, Farouque O, Andrianopoulos N, Ajani AE, Kalten K, Brennan AL, et al. The prognostic signi ﬁ cance of smoking cessation after acute coronary syndromes: an observational, multicentre study from the Melbourne interventional group registry. BMJ Open. 2017;7: e016874 . [499] Kevin C, Nicola I, Jan K, Robin PC. Evidence of poor adherence to secondary prevention after acute coronary syndromes: possible remedies through the application of new technologies. Open Heart. 2015;2: e000166 . [500] Brieger D, D ’ Souza M, Hyun K, Weaver JC, Kritharides L. Intensive lipid-lowering therapy in the 12 months after an acute coronary syndrome in Australia: an observational analysis. Med J Aust. 2019;210:80 – 5 . [501] Redfern J, Hyun K, Chew DP, Astley C, Chow C, Aliprandi-Costa B, et al. Prescription of secondary prevention medications, lifestyle advice, and referral to rehabilitation among acute coronary syndrome inpatients: results from a large prospective audit in Australia and New Zealand. Heart. 2014;100:1281 – 8 . [502] Brieger D, Chow C, Gullick J, Hyun K, D ’ Souza M, Briffa T, et al. Improving patient adherence to secondary prevention medications 6 months after an acute coronary syndrome: observational cohort study. Intern Med J. 2018;48:541 – 9 . [503] Verdicchio C, Freene N, Hollings M, Maiorana A, Briffa T, Gallagher R, et al. A clinical guide for assessment and prescription of exercise and physical activity in cardiac rehabilitation. A CSANZ position statement. Heart Lung Circ. 1035 – 1048. [504] Castellanos LR, Viramontes O, Bains NK, Zepeda IA. Disparities in cardiac rehabilitation among individuals from racial and ethnic groups and rural communities — a systematic review. J Racial Ethn Health Disparities. 2019;6:1 – 11 . [505] Smith M, Orchard J, La Gerche A, Gallagher R, Fitzpatrick J. Fit, female or ﬁ fty-is cardiac rehabilitation " ﬁ t" for purpose for all? A systematic review and meta-analysis with meta-regression. Front Cardiovasc Med. 2022;9:764882 . [506] Thomas EE, Cartledge S, Murphy B, Abell B, Gallagher R, Astley C. Expanding access to telehealth in Australian cardiac rehabilitation services: a national survey of barriers, enablers, and uptake. Eur Heart J Digit Health. 2024;5:21 – 9 . [507] Redfern J, Maiorana A, Neubeck L, Clark AM, Briffa T. Achieving coordinated secondary prevention of coronary heart disease for all in need (SPAN). Int J Cardiol. 2011;146:1 – 3 . [508] Woodruffe S, Neubeck L, Clark RA, Gray K, Ferry C, Finan J, et al. Australian Cardiovascular Health and Rehabilitation Association (ACRA) core components of cardiovascular disease secondary prevention and cardiac rehabilitation 2014. Heart Lung Circ. 2015;24:430 – 41 . [509] Briffa TG, Kinsman L, Maiorana AJ, Zecchin R, Redfern J, Davidson PM, et al. An integrated and coordinated approach to preventing recurrent coronary heart disease events in Australia. Med J Aust. 2009;190:683 – 6 . [510] Chow CK, Redfern J, Hillis GS, Thakkar J, Santo K, Hackett ML, et al. Effect of lifestyle-focused text messaging on risk factor modi ﬁ cation in patients with coronary heart disease: a randomized clinical trial. JAMA. 2015;314:1255 – 63 . [511] Pfaef ﬂ i Dale L, Whittaker R, Jiang Y, Stewart R, Rolleston A, Maddison R. Text message and internet support for coronary heart disease self-management: results from the Text4Heart randomized controlled trial. J Med Internet Res. 2015;17:e237 . [512] Varn ﬁ eld M, Karunanithi M, Lee CK, Honeyman E, Arnold D, Ding H, et al. Smartphone-based home care model improved use of cardiac rehabilitation in postmyocardial infarction patients: results from a randomised controlled trial. Heart. 2014;100:1770 – 9 . [513] World Health Organization. Classi ﬁ cation of digital health interventions v1.0. Available at: iris.who.int/bitstream/handle/10665/260480/WHORHR-18.06-eng.pdf . [accessed 1.12.24]. [514] Tromp J, Jindal D, Redfern J, Bhatt A, Severin T, Banerjee A, et al. World Heart Federation Roadmap for digital health in cardiology. Global Heart. 2022;17:61 . [515] American College of Sports Medicine. ACSM ’ s guidelines for exercise testing and prescription. 11th ed. Philadelphia, USA: Wolters Kluwer Health; 2021 . [516] Black Dog Institute. Education & services: Health professionals. Available at: www.blackdoginstitute.org.au/education-services/health-profes sionals/ . [accessed 1.12.24]. [517] Murphy BM, Higgins RO, Jackson AC, Edington J, Jackson A, Worcester MU. Patients want to know about the ’ cardiac blues ’ . Aust Fam Physician. 2015;44:826 – 32 . [518] Murphy BM, Higgins RO, Jackson AC. Incidence and impacts of postcardiac event mental health problems. Aust J Gen Pract. 2023;52:781 – 6 . [519] Beyond Blue. Available at: www.beyondblue.org.au/ . [accessed 1.12. 24]. [520] Pharmaceutical Society of Australia. Guidelines for comprehensive medication management reviews. Available at: www.ppaonline.com.au/ wp-content/uploads/2020/04/PSA-Guidelines-for-ComprehensiveMedication-Management-Reviews.pdf ; 2020. [521] Frobert O, Gotberg M, Erlinge D, Akhtar Z, Christiansen EH, MacIntyre CR, et al. In ﬂ uenza vaccination after myocardial infarction: a randomized, double-blind, placebo-controlled, multicenter trial. Circulation. 2021;144:1476 – 84 . [522] Yedlapati SH, Khan SU, Talluri S, Lone AN, Khan MZ, Khan MS, et al. Effects of in ﬂ uenza vaccine on mortality and cardiovascular outcomes in patients with cardiovascular disease: A systematic review and metaanalysis. J Am Heart Assoc. 2021;10:e019636 . [523] Australian Technical Advisory Group on Immunisation (ATAGI). Australian Immunisation Handbook. Available at: immunisationhand book.health.gov.au/ . [accessed 16.8.24]. [524] Rodriguez F, Harrington RA. Management of antithrombotic therapy after acute coronary syndromes. N Engl J Med. 2021;384:452 – 60 . [525] Benenati S, Crimi G, Canale C, Pescetelli F, De Marzo V, Vergallo R, et al. Duration of dual antiplatelet therapy and subsequent monotherapy type in patients undergoing drug-eluting stent implantation: a network meta-analysis. Eur Heart J Cardiovasc Pharmacother. 2022;8:56 – 64 . [526] Benenati S, Galli M, De Marzo V, Pescetelli F, Toma M, Andreotti F, et al. Very short vs. long dual antiplatelet therapy after second generation drug-eluting stents in 35 785 patients undergoing percutaneous coronary interventions: a meta-analysis of randomized controlled trials. Eur Heart J Cardiovasc Pharmacother. 2021;7:86 – 93 . [527] Costa F, van Klaveren D, James S, Heg D, Raber L, Feres F, et al. Derivation and validation of the predicting bleeding complications in patients undergoing stent implantation and subsequent dual antiplatelet therapy (PRECISE-DAPT) score: a pooled analysis of individual-patient datasets from clinical trials. Lancet. 2017;389:1025 – 34 . [528] Kawashima H, Gao C, Takahashi K, Tomaniak M, Ono M, Hara H, et al. Comparative assessment of predictive performance of PRECISE-DAPT, CRUSADE, and ACUITY scores in risk stratifying 30-day bleeding events. Thromb Haemost. 2020;120:1087 – 95 . [529] Costa F, Montalto C, Branca M, Hong SJ, Watanabe H, Franzone A, et al. Dual antiplatelet therapy duration after percutaneous coronary intervention in high bleeding risk: a meta-analysis of randomized trials. Eur Heart J. 2023;44:954 – 68 . [530] Garg A, Rout A, Farhan S, Waxman S, Giustino G, Tayal R, et al. Dual antiplatelet therapy duration after percutaneous coronary intervention using drug eluting stents in high bleeding risk patients: a systematic review and meta-analysis. Am Heart J. 2022;250:1 – 10 . [531] Andò G, De Santis GA, Greco A, Pistelli L, Francaviglia B, Capodanno D, et al. P2Y12 inhibitor or aspirin following dual antiplatelet therapy after percutaneous coronary intervention: A network meta-analysis. JACC: Cardiovasc Interv. 2022;15:2239 – 49 . [532] Aggarwal D, Bhatia K, Chunawala ZS, Furtado RHM, Mukherjee D, Dixon SR, et al. P2Y(12) inhibitor versus aspirin monotherapy for secondary prevention of cardiovascular events: meta-analysis of randomized trials. Eur Heart J. 2022;2:oeac019 . [533] Gragnano F, Cao D, Pirondini L, Franzone A, Kim HS, von Scheidt M, et al. P2Y(12) inhibitor or aspirin monotherapy for secondary prevention of coronary events. J Am Coll Cardiol. 2023;82:89 – 105 . [534] Bonaca MP, Bhatt DL, Cohen M, Steg PG, Storey RF, Jensen EC, et al. Long-term use of ticagrelor in patients with prior myocardial infarction. N Engl J Med. 2015;372:1791 – 800 . [535] Elliott J, Kelly SE, Bai Z, Skidmore B, Boucher M, So D, et al. Extended dual antiplatelet therapy following percutaneous coronary intervention in clinically important patient subgroups: a systematic review and metaanalysis. CMAJ Open. 2023;11:E118 – 30 . [536] 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 – 46 . [537] Lopes RD, Hong H, Harskamp RE, Bhatt DL, Mehran R, Cannon CP, et al. Optimal antithrombotic regimens for patients with atrial ﬁ brillation undergoing percutaneous coronary intervention: An updated network meta-analysis. JAMA Cardiol. 2020;5:582 – 9 . [538] Lopes RD, Leonardi S, Wojdyla DM, Vora AN, Thomas L, Storey RF, et al. Stent thrombosis in patients with atrial ﬁ brillation undergoing coronary stenting in the AUGUSTUS trial. Circulation. 2020;141:781 – 3 . [539] Alexander JH, Wojdyla D, Vora AN, Thomas L, Granger CB, Goodman SG, et al. Risk/bene ﬁ t tradeoff of antithrombotic therapy in patients with atrial ﬁ brillation early and late after an acute coronary syndrome or percutaneous coronary intervention: insights from AUGUSTUS. Circulation. 2020;141:1618 – 27 . [540] Smits PC, Frigoli E, Tijssen J, Jüni P, Vranckx P, Ozaki Y, et al. Abbreviated antiplatelet therapy in patients at high bleeding risk with or without oral anticoagulant therapy after coronary stenting: An openlabel, randomized, controlled trial. Circulation. 2021;144:1196 – 211 . [541] Yasuda S, Kaikita K, Akao M, Ako J, Matoba T, Nakamura M, et al. Antithrombotic therapy for atrial ﬁ brillation with stable coronary disease. N Engl J Med. 2019;381:1103 – 13 . [542] Urban P, Gregson J, Owen R, Mehran R, Windecker S, Valgimigli M, et al. Assessing the risks of bleeding vs thrombotic events in patients at high bleeding risk after coronary stent implantation: the ARC-high bleeding risk trade-off model. JAMA Cardiol. 2021;6:410 – 9 . [543] Cholesterol Treatment Trialists C. Effect of statin therapy on muscle symptoms: an individual participant data meta-analysis of large-scale, randomised, double-blind trials. Lancet. 2022;400:832 – 45 . [544] Navarese EP, Kowalewski M, Andreotti F, van Wely M, Camaro C, Kolodziejczak M, et al. Meta-analysis of time-related bene ﬁ ts of statin therapy in patients with acute coronary syndrome undergoing percutaneous coronary intervention. Am J Cardiol. 2014;113:1753 – 64 . [545] Mampuya WM, Frid D, Rocco M, Huang J, Brennan DM, Hazen SL, et al. Treatment strategies in patients with statin intolerance: the Cleveland Clinic experience. Am Heart J. 2013;166:597 – 603 . [546] Cannon CP, Blazing MA, Giugliano RP, McCagg A, White JA, Theroux P, et al. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med. 2015;372:2387 – 97 . [547] Schwartz GG, Steg PG, Szarek M, Bhatt DL, Bittner VA, Diaz R, et al. Alirocumab and cardiovascular outcomes after acute coronary syndrome. N Engl J Med. 2018;379:2097 – 107 . [548] Watts GF, Sullivan DR, Hare DL, Kostner KM, Horton AE, Bell DA, et al. Integrated guidance for enhancing the care of familial hypercholesterolaemia in Australia. Heart Lung Circ. 2021;30:324 – 49 . [549] Bhatt DL, Steg PG, Miller M, Brinton EA, Jacobson TA, Ketchum SB, et al. Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia. N Engl J Med. 2019;380:11 – 22 . [550] Cholesterol Treatment Trialists Collaboration, Fulcher J, O ’ Connell R, Voysey M, Emberson J, Blackwell L, et al. Ef ﬁ cacy and safety of LDLlowering therapy among men and women: meta-analysis of individual data from 174,000 participants in 27 randomised trials. Lancet. 2015;385:1397 – 405 . [551] Hay M, Stehli J, Martin C, Brennan A, Dinh DT, Lefkovits J, et al. Sex differences in optimal medical therapy following myocardial infarction according to left ventricular ejection fraction. Eur J Prev Cardiol. 2020;27:2348 – 50 . [552] Cholesterol Treatment Trialists Collaboration. Ef ﬁ cacy and safety of statin therapy in older people: a meta-analysis of individual participant data from 28 randomised controlled trials. Lancet. 2019;393:407 – 15 . [553] Bangalore S, Makani H, Radford M, Thakur K, Toklu B, Katz SD, et al. Clinical outcomes with beta-blockers for myocardial infarction: a metaanalysis of randomized trials. Am J Med. 2014;127:939 – 53 . [554] Martínez-Milla J, Raposeiras-Roubín S, Pascual-Figal DA, Ibáñez B. Role of beta-blockers in cardiovascular disease in 2019. Rev Esp Cardiol (Engl Ed). 2019;72:844 – 52 . [555] Heidenreich PA, Lee TT, Massie BM. Effect of beta-blockade on mortality in patients with heart failure: a meta-analysis of randomized clinical trials. J Am Coll Cardiol. 1997;30:27 – 34 . [556] Yndigegn T, Lindahl B, Mars K, Alfredsson J, Benatar J, Brandin L, et al. Beta-blockers after myocardial infarction and preserved ejection fraction. N Engl J Med. 2024;390:1372 – 81 . [557] Kontos MC, Diercks DB, Ho PM, Wang TY, Chen AY, Roe MT. Treatment and outcomes in patients with myocardial infarction treated with acute $\upbeta$ -blocker therapy: results from the American College of Cardiology ’ s NCDR(®). Am Heart J. 2011;161:864 – 70 . [558] Zeymer U, Bueno H, Granger CB, Hochman J, Huber K, Lettino M, et al. Acute Cardiovascular Care Association position statement for the diagnosis and treatment of patients with acute myocardial infarction complicated by cardiogenic shock: A document of the Acute Cardiovascular Care Association of the European Society of Cardiology. Eur Heart J Acute Cardiovasc Care. 2020;9:183 – 97 . [559] Hoedemaker NP, Roolvink V, de Winter RJ, van Royen N, Fuster V, García-Ruiz JM, et al. Early intravenous beta-blockers in patients undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: A patient-pooled meta-analysis of randomized clinical trials. Eur Heart J Acute Cardiovasc Care. 2020;9:469 – 77 . [560] Desta L, Raposeiras-Roubin S, Ibanez B. The art of prescribing b - blockers after myocardial infarction. Circ Cardiovasc Genet. 2021;14: e010720 . [561] Park CS, Yang HM, Ki YJ, Kang J, Han JK, Park KW, et al. Left ventricular ejection fraction 1 year after acute myocardial infarction identi ﬁ es the bene ﬁ ts of the long-term use of $\upbeta$ -blockers: Analysis of data from the KAMIR-NIH registry. Circ Cardiovasc Interv. 2021;14:e010159 . [562] Sa ﬁ S, Sethi NJ, Korang SK, Nielsen EE, Feinberg J, Gluud C, et al. Betablockers in patients without heart failure after myocardial infarction. Cochrane Database Syst Rev. CD012565. [563] Dahl Aarvik M, Sandven I, Dondo TB, Gale CP, Ruddox V, Munkhaugen J, et al. Effect of oral beta-blocker treatment on mortality in contemporary post-myocardial infarction patients: a systematic review and meta-analysis. Eur Heart J Cardiovasc Pharmacother. 2019;5:12 – 20 . [564] Franzosi M, Santoro E, Zuanetti G, Baigent C, Collins R, Flather M, et al. Indications for ACE inhibitors in the early treatment of acute myocardial infarction: systematic overview of individual data from 100,000 patients in randomized trials. Circulation. 1998;97:2202 – 12 . [565] Dagenais GR, Pogue J, Fox K, Simoons ML, Yusuf S. Angiotensin-converting-enzyme inhibitors in stable vascular disease without left ventricular systolic dysfunction or heart failure: a combined analysis of three trials. Lancet. 2006;368:581 – 8 . [566] Bangalore S, Fakheri R, Wandel S, Toklu B, Wandel J, Messerli FH. Renin angiotensin system inhibitors for patients with stable coronary artery disease without heart failure: systematic review and metaanalysis of randomized trials. BMJ. 2017;356:j4 . [567] Pfeffer MA, McMurray JJ, Velazquez EJ, Rouleau JL, Køber L, Maggioni AP, et al. Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both. N Engl J Med. 2003;349:1893 – 906 . [568] Pitt B, Remme W, Zannad F, Neaton J, Martinez F, Roniker B, et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med. 2003;348:1309 – 21 . [569] Pfeffer MA, Claggett B, Lewis EF, Granger CB, Kober L, Maggioni AP, et al. Angiotensin receptor-neprilysin inhibition in acute myocardial infarction. N Engl J Med. 2021;385:1845 – 55 . [570] Gabb GM, Mangoni AA, Anderson CS, Cowley D, Dowden JS, Golledge J, et al. Guideline for the diagnosis and management of hypertension in adults – 2016. Med J Aust. 2016;205:85 – 9 . [571] Bao YL, Gu LF, Du C, Wang YX, Wang LS. Evaluating the utility of colchicine in acute coronary syndrome: a systematic review and metaanalysis. J Cardiovasc Nurs. 2022;80:639 – 47 .

表 1
Recommendation	Strength of recommendation
ASSESSMENT AND DIAGNOSIS

In people presenting with chest pain or other symptoms suggestive of ACS, record and assess an
ECG for evidence of ACOMI within 10 minutes of first clinical contact.		Consensus

In people with suspected ACS, record and assess additional ECGs if symptoms persist, change, or		Consensus
inconclusive standard 12-lead ECG, record and assess further ECGs with right-sided and/or
posterior leads.
In people with ongoing ischaemic symptoms or haemodynamic compromise or new ischaemic
findings on ECG, continuous cardiac monitoring and defibrillator availability is recommended	Strong	LOw
while assessment for ACOMI continues.
	Biomarkers
In people with suspected ACS, evaluation with high-sensitivity cardiac troponin (hs-cTn) assays is recommended.	Strong	High
percentiles. Consensus
Apply the assay-specific troponin values relevant to the cTn assay being used.		Consensus
When evaluating changes (deltas) in troponin values, serial results from a single assay must be used.		Consensus

Risk assessment and clinical decision pathways for suspected ACS People with symptoms and ECG changes consistent with ACOMI require urgent reperfusion.	Strong
		Very Low
People presenting with acute chest pain or other symptoms suggestive of ACS should receive care		Consensus
guided by an evidence-based CDP that includes asay-specific troponin results to categorise people
as high, intermediate, or low risk.
A high-sensitivity troponin-based clinical decision pathway is recommended, using the 0/1-hour or		Consensus
0/2-hour strategy, or the High-sensitioity troponin in the eoaluation of patients with acute coronary
syndrome (High-STEACS) algorithm.

Consensus stratification is recommended.
In all people with suspected or confirmed ACS, give aspirin (300 mg orally, dissolved or chewed)	Strong	High
unless contraindicated.
People with suspected or confirmed ACS with oxygen saturation (SpO2) ≥90% do not require Oxygen therapy.	Strong	Moderate
In people with suspected or confirmed ACS receiving oxygen therapy, SpO2 should not exceed 96%.	Strong	Moderate
In the presence of ongoing chest pain, give glyceryl trinitrate sublingual tablet or spray every
		Consensus
In people with chest pain and in the absence of contraindications, it is reasonable to administer
intravenous (IV) fentanyl or morphine boluses.	Consensus

表 2
Recommendation	Strength of recommendation		Certainty of evidence

In people at intermediate risk (as defined by a validated CDP) with elevated troponin	Strong	Moderate
concentrations (>99th percentile), inpatient investigation is recommended.
In people at intermediate risk without elevated troponin concentrations, consider outpatient investigation with non-invasive testing.		Consensus
In people at low risk who remain symptom-free, further cardiac testing for CAD is not routinely required.
		Consensus
Primary care and regional and remote presentations For people with suspected ACS initially evaluated in the primary care setting, prompt transfer to a facility where definitive risk assessment can occur (e.g. ED) is recommended.
		Consensus
Metropolitan health services should establish centralised support systems for regional and remote health services to facilitate:		LOW
health services to facilitate: ● prompt assistance with ECG interpretation and accessto troponin results when on-site access is		Strong
● prompt assistance with ECG interpretation and accessto troponin results when on-site access is not available;
· provision of clinical advice to healthcare professonals;
● access to cardiac investigations if required.
HOSPITAL CARE AND REPERFUSION	Acute management of STEMI Eligibility for reperfusion

In people with STEMI within 12 hours of symptom onset, perform emergency reperfusion with either primary PCI or fbrinolytic therapy.		Strong	Moderate
In people with STEMI, symptom onset over 12 hours before presentation and evidence of		Strong	Moderate
continuing myocardial ischaemia (persistent ischaemic symptoms, haemodynamic compromise, and/or li-threatening arrhythmias) perform emergency reperfusion with primary PCI
	Choice of reperfusion strategy
In people with STEMI within 12 hours of symptom onset, primary PCI is the preferred reperfusion strategy over fibrinolysis, if it can be performed within 120 minutes of first medical contact.		Strong	High
In people with STEMI within 12 hours of symptom onset, perform fibrinolysis if primary PCI cannot
be delivered within 120 minutes of first medical contact.		Strong	Moderate
	Administration of fibrinolytic therapy
	In people with STEMI for whom fibrinolysis is the preferred reperfusion strategy, it should be Strong		Moderate
delivered within 30 minutes of first medical contact. Consider pre-hospital administration.
In people aged ≥70 years, half the standard dose of tenecteplase is recommended as part of a pharmaco-invasive strategy.		Strong	Moderate

Procedural recommendations in primary percutaneous coronary intervention For people with STEMI at a PCI-capable centre, deliver primary PCI within 60 minutes of arrival.
For people with STEMI transferred from a non-PCI centre, deliver primary PCI within 90 minutes of first hospital arrival.		Consensus

Use radial access over femoral access when performing primary PCI, unless contraindicated.		Strong.	High
In people undergoing primary PCI, do not perform routine thrombus aspiration of the infarct- related artery (IRA).	Strong		Moderate
In people who are asymptomatic and stable for more than 48 hours following occlusion of an IRA, Strong
			Moderate
do not perform routine PCI to this artery.

表 3
Recommendation	Strength of recommendation	Certainty of evidence
Ongoing management of fibrinolytic-treated people
People successfully treated with fibrinolytic therapy should be transferred to a PCI-capable centre as	Strong	Moderate
soon as possible. Angiography should be performed within 2-24 hours of arrival. Consider transferring people as soon as possible to a PCI-capable centre if fibrinolytic therapy is
	Weak		Moderate
Acute management of NSTEACS

In people with NSTEACS, consider using the GRACE risk score to determine short- and long-term	Weak		High
cardiovascular prognosis.		Moderate
In people with ACS undergoing coronary angiography, consider using bleeding risk scores to Weak determine short-term bleeding risk.
Routine versus selective invasive management for NSTEACS
In people with NSTEACS at high or very high-risk of adverse cardiovascular events, perform	Strong		High
routine invasive coronary angiography, with coronary revascularisation (PCI or CABG) where appropriate.
In people with NSTEACS not at high or very high risk of adverse cardiovascular events, testing for Weak Moderate inducible ischaemia (e.g. stress testing) may guide the need for invasive coronary angiography.
	Timing of invasive management for NSTEACS
In people with NSTEACS with very high-risk criteria, an immediate invasive strategy within 2 hours of diagnosis is recommended.		Consensus

In people with NSTEACS with high-risk criteria, consider an early invasive strategy within 24 hours	Weak	High
	Procedural considerations in NSTEACS
In people with NSTEACS undergoing an invasive approach, radial access is preferred to femoral	Strong	High
access, unless contraindicated.
In people with NSTEACS undergoing an invasive approach, consider intravascular imaging to guide PCI.	Weak	High

In people with STEMI treated with fibrinolytic therapy, give dual antiplatelet therapy with aspirin and clopidogrel.	Strong	Moderate

In people with STEMI undergoing primary PCI and people with NSTEACS undergoing a routine invasive strategy, give dual antiplatelet therapy with aspirin and a potent P2Y2 inhibitor ticagrelor	Strong	High
or prasugrel).
In people with STEMI undergoing primary PCI and people with NSTEACS undergoing a routine	Strong	High
invasive strategy for whom ticagrelor or prasugrel are contraindicated, and those receiving oral anticoagulation, give clopidogrel.

In people with NSTEACS for whom a selective invasive strategy is planned, give ticagrelor or clopidogrel.	Strong	High
In people with NSTEACS, consider routine genotypic or platelet function guidance of P2Y12 therapy.	Weak	Moderate

In people with NSTEACS, consider de-escalation from potent P2Y12 inhibitor to clopidogrel, but not Weak Moderate
during the first 30 days following an ACS event.

表 4
(continued).
Recommendation	Strength of recommendation	Certainty of evidence
In people with ACS with concomitant non-valvular atrial fibrillation and CHA2DS2VA score >1,	Strong	High
give aspirin and clopidogrel, together with a non-vitamin K oral anticoagulant.
In people with STEMI undergoing primary PCI or those with NSTEACS undergoing an invasive		Consensus
strategy, routine glycoprotein Ila/ inhibitor (GPI) is not recommended.
People treated with fibrinolytic therapy should receive anticoagulation (unfractionated heparin or		Strong	Moderate

People undergoing primary PCI should receive anticoagulation (unfractionated heparin or bivalirudin).		Strong	Moderate

People with NSTEACS should receive anticoagulation (unfractionated heparin, enoxaparin, or	Strong		LOW
	Acute management of ACS with cardiac arrest
In people with return of spontaneous circulation after resuscitated cardiac arrest and persistent STE on ECG, perform emergency reperfusion.	Strong		LOW
	Strong		Moderate
In haemodynamically stable people with resuscitated cardiac arrest and no STE on ECG, do not perform routine emergency coronary angiography.
In people with ACS and cardiogenic shock, perform PCI of the IRA only.	Acute management of ACS with cardiogenic shock	Strong.	Moderate
In people with ACS and cardiogenic shock, routine insertion of an intra-aortic balloon pump is not			High
recommended.		Strong
In people with ACS and cardiogenic shock, routine venoarterial extracorporeal membrane		Strong	Moderate
In select people with STEMI and cardiogenic shock, consider left ventricular assist devices.		Weak	Moderate
Treatment for ACS with multivessel disease without cardiogenic shock
In haemodynamically stable people with STEMI and MVD, perform PCI of suitable non-IRA(s).		.Strong.	High
		Weak	Moderate

In people with STEMI and MVD, routine invasive physiology assessment (e.g. fractional flow		Consensus
In people with NSTEACS and non-complex MVD, consider routine PCI of non-IRA in the same .setting.	Weak	LOW
In people with NSTEACS and MVD, consider invasive physiology assessment (e.g. FFR) to evaluate non-IRA severity.	Weak	LOW

In people with STEMI, mechanical complications and mitral valve disease (e.g. ventricular septal	Coronary artery bypass graft surgery in ACS
rupture, mitral valve insufficiency because of papillary muscle infarction or rupture, or free wall rupture), perform CABG at the time of surgery.	Strong	LOW

Treatment for spontaneous coronary artery dissection In people with ACOMI due to SCAD but who are otherwise stable, routine revascularisation is not		Consensus
recommended.
In people with SCAD and haemodynamic instability and/or ongoing ischaemia, consider selective weak VeryLow
revascularisation.
Recommendation	Strength of recommendation	Certainty of evidence
RECOVERY AND SECONDARY PREVENTION Person-centred non-pharmacological secondary prevention
For all people with ACS, refer to a multi-disciplinary exercise-based cardiac rehabilitation program prior to discharge.	Strong	Moderate

For all people with ACS, provide advice on lifestyle* changes such as healthy eating, regular		Consensus
physical activity, not smoking, limiting alcohol intake, and caring for mental health.
For all people with ACS who smoke, advise to stop and refer for behavioural intervention (such as Strong			Moderate
cognitive behaviour therapy or cessation counselling program), combined with pharmacotherapy
where appropriate (nicotine replacement therapies, varenicline and bupropion individually or in combination).

For all people with ACS, implement strategies to optimise adherence to preventive medicines. For all people with ACS, implement strategies to optimise adherence to preventive medicines. Consensus Vaccination against influenza and other respiratory pathogens
In people with CS, vaccinations forinfuenza and other respiratory pathogens are recommended.		Consensus

Post-ACS pharmacotherapy Antiplatelet therapy	Strong
In people discharged following an ACS who are at high ischaemic and/or low bleeding risk, prescribe DAPT with aspirin and a P2Y12 inhibitor for 6-12 months.		High
In people discharged following an ACS who are at low ischaemic and/or high bleeding risk, cease	Strong	High
DAPT at 1-3 months post-ACS and continue single antiplatelet therapy (SAPT).
In people discharged following an ACS who have completed a course of DAPT (i.e. 1-12 months),. Strong		Moderate

In people discharged following an ACS who remain at high ischaemic and low bleeding risk, consider long-term DAPT (>12 months).	Weak	Moderate

In people discharged following an ACS with an indication for long-term OAC therapy, continue	Strong	High
OAC and DAPT (preferentially aspirin and clopidogrel) for 1-4 weeks, then cease aspirin.
In people discharged following an ACS with an indication for long-term OAC therapy, cease	Strong	Moderate
antiplatelet therapy at 6-12 months and continue anticoagulation alone.
	Lipid-modifying therapy
In people with ACS, prior to hospital discharge, initiate and continue indefinitely, the highest	Strong	High
tolerated dose of HMG-CoA reductase inhibitors (statins), unless contraindicated or completely statin intolerant.
In people with ACS with initial or partial intolerance to statin, consider using a different statin, dose	Weak
or dosing frequency to achieve person-specific therapeutic objectives.		LOW
In people with ACS, an initial target low density lipoprotein cholesterol (LDL-C) level of		Consensus

表 6
(continued).
Recommendation	Strength of recommendation		Certainty of evidence
In people with ACS with a suboptimal LDL-C level despite maximally tolerated statin therapy and ezetimibe, give PCSK9 inhibitors.		Strong	High

Beta blocker therapy	Beta blocker therapy
In people with ACS and LV impairment, beta blockers are recommended.		Consensus	Consensus
In people with ACS and preserved LV systolic function who have undergone coronary			Moderate
revascularisation and are receiving optimal medical therapy, consider withholding beta blockers.
Renin-angiotensin antagonist therapies	Strong	High
chronic kidney disease, initiate and continue angiotensin converting enzyme (ACE) inhibitors, or

In people with ACS and LVEF

表 7
Certainty of evidence

The certainty of evidence reflects the extent to which the confidence in the estimates of an effect is adequate to support a particular decision. Certainty of	What it means
evidence
High	The authors are very confident that the true effect lies close to that of the estimate of the effect.
Moderate	The authors are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
LOW
	The authors' confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect.
Verylow	The authors have very little confidence in the effect estimate: the true effect is likely to be substantially
	differentfrom the estimate of the effect.
Strength of recommendation
	The strength of a recommendation reflects the extent to which the authors are confident that desirable effects of an intervention outweigh
undesirable effects, or vice versa, across the range of people for whom the recommendation is intended. It is determined by considering the
balance between benefits and harms, certainty of evidence, variability or uncertainty in the values and preferences of the target population, and resource use.

Strength of	What it means
recommendation
Strong	The authors are confident that the desirable effects of adherence to a recommendation outweigh the
	undesirable effects. It implies that most or all individuals will be best served by the recommended course of action.
Weak	The authors concluded that the desirable effects of adherence to a recommendation probably outweigh the
	undesirable effects but are not certain. It implies that not all individuals will be best served by the

表 8
Cardiac: ACS	AMI, unstable angina.
Cardiac: Other	Stable angina, myopericarditis,
	tachyarrhythmia, hypertensive emergencies,
	severe aortic stenosis, Takotsubo
	cardiomyopathy, cardiac trauma.
Pulmonary	Pulmonary embolism, pneumothorax
	(including tension), infection (pneumonia,
	bronchitis), pleuritis.
Vascular	Aortic dissection, expanding aortic
aneurysm, sickle cell crisis.

	Gastrointestinal Oesophagitis, reflux, spasm, rupture, peptic
	ulcer disease, pancreatitis, cholecystitis and
	biliary disease.
Other	Musculoskeletal disease (including
	costochondritis, trauma), anxiety disorder,

	infectious disease (including herpes zoster).

表 9
Recommendation	Strength of recommendation	Certainty O1 evidence

In people presenting with	Consensus
chest pain or other symptoms
suggestive of ACS, record and
assess an ECG for evidence of
ACOMI within 10 minutes of
first clinical contact.

In people with suspected ACS,	Consensus
record and assess additional
ECGs if symptoms persist,
change, or recur, or there is
diagnostic uncertainty. For
those with ongoing ischaemic
symptoms and an inconclusive
standard 12-lead ECG, record
and assess further ECGs with
right-sided and/or posterior
leads.
In people with ongoing	Strong	LOW
ischaemic symptoms or
haemodynamic compromise
or new ischaemic findings on
ECG, continuous cardiac
monitoring and defibrillator
availability is recommended
while assessment for ACOMI
continues.

表 10
	Criteria	Supporting information and illustration
A.Regional STE with reciprocal STD	STE ≥1 mm at the J-point in two contiguous leads in all leads other than V2-4.	Normal	Activate reperfusion pathway


B. High lateral MI	STE I, aVL, V2 STD III(+/-II, aVF) Subtle STE V5, V6 and reciprocal changes in aVF may be seen.		Activate reperfusion pathway
C.Posterior MI	Precordial STD ≥0.5 mm V1-3 Confirm with posterior leads (V7,8,9) with findings of STE: ≥0.5 mm in women and men ≥40 years	V7,8,9 supplementary lead placement	Activate reperfusion pathway

D. Right ventricular	STE ≥0.5 mm in any right-sided chest lead (V3R-V6R), but particularly V4R.	Right precordial supplementary lead placement	Activate reperfusion pathway
E.De Winter Twaves	STE ≥1 mm in men

表 11
Cardiac region	Leads with STE	Reciprocal STD

Anterior	V3，V4	None
Anterolateral	1, aVL V3-V6	I1, III aVF
Anteroseptal	V1-V4	None
Septal	V1，V2	None
Inferior	II, III, aVF	I,aVL
Right ventricular	Right-sided
	chest leads V3-6
Posterior	Posterior leads V7-9	V1-V3
Lateral	I, aVL,V5, V6	I1, III, aVF
High lateral	1,aVL (V2)	III (II, aVF)

表 12
	Criteria	Supporting information and illustration	Recommendation for clinical action
A.Wellens criteria	Isoelectricorminimallyelevated J-point
A.Wellens criteria	Isoelectricorminimallyelevated J-point
A.Wellens criteria	Isoelectricorminimallyelevated J-point
A.Wellens criteria	Isoelectricorminimallyelevated J-point

表 13
Recommendation	Strength of recommendation	Certainty of evidence High

In people with	Strong
suspected ACS,
evaluation with
high-sensitivity cardiac
troponin (hs-cTn)

Elevated hs-cTn values	Consensus
should be defined using
sex-specific >99th
percentiles.
Apply the assay-	Consensus	Consensus
specific troponin values
relevant to the cTn
assay being used.

When evaluating	Consensus
changes (deltas) in
troponin values, serial
results from a single
assay must be used.

表 14
Characteristic	Contemporary troponin assays*	High-sensitivity troponin assays
Precision	Variable	≤10% CV at 99thpercentile
Detection ~ 20-50% of healthy reference population

Sex-specific 99th percentiles	No. Overall 99th percentile values only Yes. Female and male 9gth percentiles
Timing of serial testing for MI using	0 and 6-8 hours	0 and 3 hours
	70
Single low-risk troponin values for MI* Ability to use in rapid, early assessment		Yes
strategies	70	Yes
Platform

表 15
Assay	Sampling timepoints		B
							Female 99th percentile	Male 99th percentile
Hs-cTnI (Architect; Abbott)	0/1h	人4	人5	人M	≥64	¥Z6	16	34
	0/2h	人4

表 16
Recommendation	Strength of recommendation	Certainty of evidence
	Strong
People with symptoms		VeryLow
and ECG changes
consistent with ACOMI
require urgent
reperfusion. Do not use
clinical decision pathway

People presenting with		Consensus
acute chest pain or other
symptoms suggestive of
ACS should receive care
guided by an evidence-
based CDP that includes
assay-specific troponin
results to categorise
people as high,
intermediate, or low risk.
A high-sensitivity	Consensus
troponin-based clinical
decision pathway is
recommended, using the
0/1-hour or 0/2-hour
strategy, or the High-
sensitioity troponin in the
evaluation of patients with
acute coronary syndrome
(High-STEACS) algorithm.

When contemporary	Consensus
troponin assays are used, a
CDP incorporating formal clinical score-based risk
stratification is
recommended.

表 17
Clinical manifestation	Possible causesofelevation	Possible mechanism Necrosis Apoptosis and necroptosis Reversible troponin leakage (cell stretching, cell wounds, bleb formation)
ANI	ANI	Possible mechanism Necrosis Apoptosis and necroptosis Reversible troponin leakage (cell stretching, cell wounds, bleb formation)	Prolonged ischaemia	Prolonged ischaemia
Acute HF	Acute HF	Possible mechanism Necrosis Apoptosis and necroptosis Reversible troponin leakage (cell stretching, cell wounds, bleb formation)	Prolonged ischaemia	Prolonged ischaemia
Pulmonary embolism	Pulmonary embolism	Possible mechanism Necrosis Apoptosis and necroptosis Reversible troponin leakage (cell stretching, cell wounds, bleb formation)	Prolonged ischaemia	Prolonged ischaemia
Chest trauma or surgery	Mechanical cell destruction, local inflammation	Possible mechanism Necrosis Apoptosis and necroptosis Reversible troponin leakage (cell stretching, cell wounds, bleb formation)
Stroke or brain trauma	Catecholamine-derived myocyte overload or ischaemia due to type 2 MI	Possible mechanism Necrosis Apoptosis and necroptosis Reversible troponin leakage (cell stretching, cell wounds, bleb formation)
Cardiotoxicity	Cardiotoxicity	Possible mechanism Necrosis Apoptosis and necroptosis Reversible troponin leakage (cell stretching, cell wounds, bleb formation)	Cardiotoxic agents (drugs, CO, poisons)
Myocarditis, endocarditis	Inflammation	Inflammation
Sepsis	Sepsis	Inflammation
Atrial fibrillation	Atrial fibrillation	Possible mechanism Necrosis Apoptosis and necroptosis Reversible troponin leakage (cell stretching, cell wounds, bleb formation)	Brief ischaemia Muscle overload
Chronic HF	Chronic HF	Possible mechanism Necrosis Apoptosis and necroptosis Reversible troponin leakage (cell stretching, cell wounds, bleb formation)	Brief ischaemia Muscle overload
Chronic HF	Chronic HF	Possible mechanism Necrosis Apoptosis and necroptosis Reversible troponin leakage (cell stretching, cell wounds, bleb formation)	Brief ischaemia Muscle overload
StableCAD	StableCAD	Possible mechanism Necrosis Apoptosis and necroptosis Reversible troponin leakage (cell stretching, cell wounds, bleb formation)	Brief ischaemia Muscle overload
Physical exercise	Physical exercise	Possible mechanism Necrosis Apoptosis and necroptosis Reversible troponin leakage (cell stretching, cell wounds, bleb formation)	Brief ischaemia Muscle overload
Renal failure	Renal failure	Possible mechanism Necrosis Apoptosis and necroptosis Reversible troponin leakage (cell stretching, cell wounds, bleb formation)	Impaired clearance	Impaired clearance
Skeletal muscle disorders	Expression of cTnT in regenerative skeletal muscles	Possible mechanism Necrosis Apoptosis and necroptosis Reversible troponin leakage (cell stretching, cell wounds, bleb formation)

表 18
Recommendation	Strength of	Certainty of
	recommendation evidence
In all people with suspected	dStrong	High
or confirmed ACS, give
aspirin (300 mg orally,
dissolved or chewed) unless
contraindicated.

People with suspected or	Strong	Moderate
confirmed ACS with oxygen
saturation (SpO2) ≥90% do
not require oxygen therapy.
In people with suspected or	Strong	Moderate
confirmed ACS receiving
oxygen therapy, SpO2
should not exceed 96%.

表 19
(continued).
Recommendation	Strength of Certainty of recommendation1evidence
In the presence of ongoing	Consensus
chest pain, give glyceryl
trinitrate sublingual tablet or
spray every 5 minutes for up
to three doses if no
contraindications exist.

In people with chest pain	Consensus
and in the absence of
contraindications, it is
reasonable to administer
intravenous (IV) fentanyl or
morphine boluses.

表 20
Recommendation	Strength of recommendation		Certainty
Recommendation	Strength of recommendation		O1 evidence

In people at intermediate risk		Strong	Moderate
(as defined by a validated
CDP) with elevated troponin
concentrations (>99th
percentile), inpatient
investigation is recommended.
In people at intermediate risk		Consensus
without elevated troponin
concentrations, consider
outpatient investigation with
non-invasive testing.

In people at low risk who		Consensus
remain symptom-free, further
cardiac testing for CAD is not
routinely required.

表 21
Ischaemic test modality	Strengths	Considerations for use
	·Low cost	● Decreased accuracy compared
Exercise stress ECG	● Wide availability	with anatomical and	· Rarely recommended as a
	● Assessment of exercise	stress-imaging tests	stand-alone test in people
	symptoms, capacity	● Requires interpretable ECG	with known CAD, inability to exercise, or significant
	● No ionising radiation	and ability to exercise sufficiently
			arrhythmias
		● Higher false positive rate in females	· Contraindicated in severe symptomatic aortic stenosis
			or severe hypertension
Stress	● Wide availability	● Decreased sensitivity compared
echocardiography	● High diagnostic specificity	with anatomical and other	· Known good image quality and ability to exercise
echocardiography	● Assessment of ventricular	stress-imaging tests	Consider use of an ultrasound-
	and valvular function	· Dependent on good image quality	enhancing agent to improve
	● No ionising radiation	·● Requires dobutamine in people unable to exercise	endocardial visualisation
			● Known moderate or severe valvular disease
	● Wide availability	· Increased artefacts resulting	· Known CAD or high coronary
Stress/rest SPECT	● Relatively high diagnostic sensitivity	in non-diagnostic results	artery calcification burden on
Stress/rest SPECT		and decreased diagnostic	chest computed tomography
	· Assessment of ventricular function	accuracy compared with	(CT) imaging
	· Assessment of ventricular function		● Preferred over stress
			echocardiography in people who
			cannot exercise or who have
			significant exercise-induced
			bronchospasm
Stress/rest PET	● High diagnostic accuracy	● Limited availability	· Known CAD or high coronary
	● Lower radiation exposure than SPECT	· Relatively higher cost	artery calcification burden on
	than SPECT ● Measures myocardial blood	● Lack of exercise assessment	chest CT imaging
		● Lack of exercise assessment	● Preferred over SPECT due to
	flow and flow reserve		higher diagnostic accuracy
	· Assessment of ventricular		and lower rate of nondiagnostic
	function		test results

表 22
Ischaemic test modality	Strengths	Limitations		Considerations for use
Stress CMR	● High diagnostic accuracy	● Limited availability		● Known CAD and/or
	· Accurate assessment of		· Relatively higher cost	cardiomyopathy
	chamber sizes, ventricular		· Lack of exercise assessment	● Elevated troponin not thought
	and valvular function		· Long scan acquisition times	to be secondary to ACS
		● Diagnosis of prior infarction,	· Claustrophobia	● Known moderate or severe
	scar, fibrosis		· Often not immediately	valvular disease
		· Measurement of myocardial	available to people with pacemakers or ICDs	· No significant renal dysfunction
		blood flow and flow reserve
		is possible (but not Contraindicated in people with significant renal dysfunction
		widely available currently)
	· No ionising radiation
· High diagnostic accuracy	· Radiation exposure ● Lack of exercise assessment		● No known CAD
● Does not require exercise			· Absence of severe coronary
● Identifies non-obstructive		0 Contraindicated in people with significant renal dysfunction	calcification
			· Prior normal, mildly abnormal, or inconclusive stress test results
	Blooming artefacts when significant coronary calcification present		· No known iodinated contrast
				medium allergy or significant
		● Atrial fibrillation or other		renal dysfunction
		· May require beta blockers		● Low likelihood of high-quality
				stress testing or lack of
		● Incidental non-cardiac findings		timely access

表 23
Recommendation	Strength of recommendation	Certainty of nevidence
For people with suspected	Consensus
ACS initially evaluated in
the primary care setting.
prompt transfer to a facility
where definitive risk
assessment can occur
(e.g. ED) is recommended.
Metropolitan health services	Strong	LOW
should establish centralised
support systems for regional
and remote health services
to facilitate:
prompt assistance with
ECG interpretation and
access to troponin results
when on-site access is
not available
provision of clinical advice
to healthcare professionals
· access to cardiac
investigations if required.

表 24
Recommendation	Strength of recommendation	Certainty of evidence
	Strong	Moderate
In people with STEMI within 12 hours of		Moderate
symptom onset, perform
emergency reperfusion
with either primary PCI
or fibrinolytic therapy.
In people with STEMI,	Strong	Moderate
symptom onset over		Moderate
12 hours before		Moderate
presentation and		Moderate
evidence of continuing
myocardial ischaemia
(persistent ischaemic
symptoms,
haemodynamic
compromise, and/or
life-threatening
arrhythmias),
perform emergency
reperfusion with
primary PCI.

表 25
Recommendation	Strength of recommendation
		Certainty of evidence
In people with STEMI	Strong	High
within 12 hours of
symptom onset, primary
PCI is the preferred
reperfusion strategy
over fibrinolysis, if it
can be performed within
120 minutes of first
medical contact.

In people with STEMI	Strong	Moderate
within 12 hours of
symptom onset, perform
fibrinolysis if primary
PCI cannot be delivered
within 120 minutes of
first medical contact.

表 26
Recommendation	Strength of
	recommendation	Certainty of evidence
In people with STEMI	Strong	Moderate
for whom fibrinolysis
is the preferred
reperfusion strategy,
it should be delivered
within 30 minutes of
first medical contact.
Consider pre-hospital
administration.

In people aged	Strong	Moderate
>70 years, half the
standard dose of
tenecteplase is
recommended as part
of a pharmaco-invasive
strategy.

表 27
Recommendation	Strength of recommendation	Certainty of evidence
For people with STEMI	Consensus
at a PCI-capable centre,
deliver primary PCI
within 60 minutes of
arrival. For people with
STEMI transferred
from a non-PCI centre,
deliver primary PCI
within 90 minutes of
first medical contact.
Use radial access over	Strong	High
femoral access when
performing primary
PCI, unless
contraindicated.
In people undergoing	Strong
		Moderate
primary PCI, do not
perform routine thrombus aspiration
of the infarct-related
artery (IRA).

	Strong
asymptomatic and
stable for more than 48 hours following
occlusion of an IRA,
do not perform routine
PCI to this artery.

表 28
Recommendation	Strength of	Certainty of evidence
	recommendation
People successfully	Strong	Moderate
treated with fibrinolytic
therapy should be
transferred to a PCI-
capable centre as soon
as possible. Angiography
should be performed
within 2-24 hours of
arrival.

Consider transferring	Weak	Moderate
people as soon as
possible to a PCI-capable
centre if fibrinolytic
therapy is unsuccessful.
If appropriate, consider
subsequent PCI at
the centre.

表 29
Recommendation	Strength of	Certainty of evidence High
	recommendation	Certainty of evidence High
In people with NSTEACS,	Weak	Certainty of evidence High
consider using the GRACE		Certainty of evidence High
risk score to determine		Certainty of evidence High
short- and long-term		Certainty of evidence High
cardiovascular prognosis.

In people with ACS		Moderate
undergoing coronary
angiography, consider
using bleeding risk
scores to determine
short-term bleeding risk.

表 30
Recommendation	Strength of recommendation	Certainty of evidence
In people with	Strong	High
NSTEACS at high or
very high risk of
adverse cardiovascular
events, perform routine
invasive coronary
angiography, with
coronary
revascularisation (PCI
or CABG) where
appropriate.

In people with	Weak	Moderate
NSTEACS not at high
or very high risk of
adverse cardiovascular events, testing for
inducible ischaemia

(e.g. stress testing) may guide the need for

invasive coronary angiography.

表 31
Recommendation	Strength of	Certainty of
Recommendation	recommendation	evidence
In people with	Consensus

NSTEACS with very
high-risk criteria, an
immediate invasive
strategy within 2
hours of diagnosis is
recommended.

表 32
(continued).
Recommendation	Strength of recommendation	Certainty of evidence High
		Certainty of evidence High
In people with	Weak
NSTEACS with
high-risk criteria,
consider an early
within 24 hours of diagnosis.
within 24 hours of diagnosis.
within 24 hours of diagnosis.

表 33
Recommendation	Strength of recommendation	Certainty O1 evidence
Recommendation	Strength of recommendation	Certainty O1 evidence

In people with NSTEACS	Strong	High
undergoing an invasive
approach, radial access
is preferred to femoral
access, unless contraindicated.
In people with NSTEACS	weak	High
undergoing an invasive
approach, consider

intravascular imaging to guide PCI.

表 34
(continued).
Recommendation	Strength of Certainty of recommendationnevidence
In people with STEMI	Consensus	Consensus
undergoing primary PCI or
those with NSTEACS
undergoing an invasive

strategy, routine glycoprotein HIa/IIb inhibitor (GPI) is not
recommended.

表 35
Recommendation	Strength of
	recommendation	Certainty of evidence
		Moderate
People treated with	Strong
fibrinolytic therapy
should receive
anticoagulation
(unfractionated heparin
or enoxaparin).
People undergoing	Strong	Moderate
primary PCI should		Moderate
receive anticoagulation
(unfractionated heparin
or bivalirudin).
People with NSTEACS	Strong
should receive		LOW
anticoagulation		LOW
(unfractionated
heparin, enoxaparin, or
fondaparinux).
	recommendation	Certainty of evidence
	Strong
In people with return of		LOW
spontaneous circulation
after resuscitated
cardiac arrest and
persistent STE on ECG, perform emergency
reperfusion.

表 37
(continued).
Recommendation	Strength of recommendation	Certainty of evidence
In haemodynamically	Strong
stable people with		Moderate
resuscitated cardiac
arrest and no STE on
ECG, do not perform
routine emergency
coronary angiography.

表 38
Recommendation	Strength of	Certainty of evidence
	recommendation
In people with ACS and	Strong	Moderate
cardiogenic shock, perform
PCI of the IRA only.

表 39
(continued).
Recommendation	Strength of recommendation	Certainty of evidence High
		Certainty of evidence High
In people with ACS and	Strong	Certainty of evidence High
cardiogenic shock, routine		Certainty of evidence High
insertion of an intra-aortic
balloon pump is not
recommended.
In people with ACS and	Strong	Moderate
cardiogenic shock, routine
venoarterial extracorporeal
membrane oxygenation is
not recommended.

In select people with	Weak	Moderate
STEMI and cardiogenic		Moderate
shock, consider left ventricular assist devices.

表 40
Recommendation	Strength of recommendation	Certainty of evidence

In haemodynamically	Strong	High

stable people with
STEMI and MVD,
perform PCI of
suitable non-IRA(s).
Consider performing	Weak	Moderate
PCI of the non-IRA at
the time of primary
PCI or within 19 days
of the index
procedure.
In people with STEMI		Consensus
and MVD, routine
invasive physiology
assessment (e.g.
fractional flow reserve
[FFR]) to evaluate
non-IRA severity is
not recommended.
In people with	Weak	LOW
NSTEACS and non-
complex MVD,
consider routine PCI
of non-IRA in the
same setting.

In people with	weak	LOW
NSTEACS and MVD,
consider invasive
physiology
assessment (e.g. FFR)
to evaluate non-IRA
severity.

表 41
Recommendation	Strength of	Certainty of evidence

In people with STEMI,	Strong	LOW
mechanical
complications and
mitral valve disease
(e.g. ventricular septal
rupture, mitral valve
insufficiency because of
papillary muscle
infarction or rupture, or
free wall rupture),
perform CABG at the
time of surgery.

表 42
Recommendation	Strength of
	recommendation	Certainty of evidence

In people with ACOMI	Consensus
due to SCAD but who
are otherwise stable,
routine
revascularisation is not
recommended.
In people with SCAD	Weak	VeryLow
and haemodynamic
instability and/or
ongoing ischaemia,
consider selective
revascularisation.

表 43
Recommendation	Strength of recommendation	Certainty of evidence
For all people with ACS,	Strong	Moderate
refer to a multi-disciplinary
exercise-based cardiac
rehabilitation program
prior to discharge.

For all people with ACS,		Consensus
provide advice on lifestyle*
changes such as healthy
eating, regular physical
activity, not smoking,
limiting alcohol intake, and
caring for mental health.
For all people with ACS	Strong	Moderate
who smoke, advise to stop
and refer for behavioural
intervention (such as
cognitive behaviour
therapy or cessation
counselling program),
combined with
pharmacotherapy where
appropriate (nicotine
replacement therapies,
varenicline and bupropion
individually or in
combination).
For all people with ACS,	Consensus
implement strategies to
optimise adherence to
preventive medicines.

表 44
Recommendation	Strength of	Certainty of
	recommendation	evidence
In people with ACS,	Consensus
vaccinations for
influenza and other
respiratory pathogens
are recommended.

表 45
Recommendation	Strength of recommendation
Recommendation	Strength of recommendation	Certainty OF evidence

In people discharged	Strong	High
following an ACS who are at
high ischaemic and/or low
bleeding risk, prescribe DAPT
with aspirin and a P2Y12
inhibitor for 6-12 months.

In people discharged	Strong	High
following an ACS who are at
low ischaemic and/or high
bleeding risk, cease DAPT at
1-3 months post-ACS and
continue single antiplatelet

表 46
(continued).
Recommendation	Strength of	Certainty OF
	recommendation
		evidence
In people discharged	Strong	Moderate
following an ACS who have
completed a course of DAPT
(i.e. 1-12 months), prescribe
long-term P2Y12 inhibitor over

In people discharged	Weak	Moderate
following an ACS who remain
at high ischaemic and low
bleeding risk, consider long-
term DAPT (>12 months).
In people discharged	Strong
following an ACS with an		High
indication for long-term OAC
therapy, continue OAC and
DAPT (preferentially aspirin
and clopidogrel) for 1-4
weeks, then cease aspirin.

In people discharged	Strong	Moderate
following an ACS with an
indication for long-term OAC
therapy, cease antiplatelet therapy at 6-12 months and

continue anticoagulation
alone.

表 47
Table 11	Determinants of recurrent ischaemic risk
following an ACS [343,408].
	High ischaemic risk	Persisting high ischaemic risk
Aged

表 48
Recommendation	Strength of recommendation	Certainty OF evidence
In people with ACS, prior to hospital discharge, initiate and	Strong	High

continue indefinitely, the
highest tolerated dose of
HMG-CoA reductase
inhibitors (statins), unless
contraindicated or completely
statin intolerant.
In people with ACS with	Weak	LOW
initial or partial intolerance to
statin, consider using a
different statin, dose or dosing
frequency to achieve person-
specific therapeutic objectives.
In people with ACS, an initial	Consensus
target low density lipoprotein
cholesterol (LDL-C) level of

表 49
Recommendation
	Strength of Certainty recommendationnof Evidence
In people with ACS and LV
impairment, beta blockers are
recommended.

表 50
(continued).
Recommendation	Strength of	Certainty of Evidence
	recommendation
In people with ACS and	Weak	Moderate
preserved LV systolic
function who have
undergone coronary
revascularisation and are
receiving optimal medical
therapy, consider
withholding beta blockers.

表 51
Recommendation	Strength of
	recommendation	Certainty of Evidence
In people with ACS and	Strong	High
heart failure symptoms,
LVEF

表 52
(continued).
Recommendation	Strength of	Certainty of Evidence
	recommendation
In people with ACS and	Strong	High
LVEF ≤40% and heart
failure with or without
diabetes, initiate and
continue
mineralocorticoid
receptor antagonists.
In people with ACS, use	Strong	High
of an angiotensin		High
receptor-neprilysin
inhibitor is not
recommended.

表 53
Recommendation	Strength of	Certainty of evidence

In people with ACS,	Weak	Moderate
consider initiating
colchicine (0.5 mg daily)
and continuing long-term
unless contraindicated or
colchicine intolerant.

表 54
ACE	angiotensin converting enzyme
ACOMI	acute coronary occlusion myocardial infarction
ACS	acute coronary syndromes
ACTION	Acute coronary treatment and intervention outcomes network
ACUITY	Acute catheterization and urgent intervention triage strategy
AMI	acute myocardial infarction
ARC-HBR	Academic Research Consortium high bleeding risk
CABG	coronary artery bypass grafting
CAD	coronary artery disease
CDP	clinical decision pathway
CH	confidence interval
CK-MB	creatine kinase MB-isoenzyme
COPD	chronic obstructive pulmonary disease
CRUSADE	Can rapid risk stratification of unstable angina patients suppress adverse outcomes with early implementation of the ACC/AHA guidelines

CSANZ	Cardiac Society of Australia and New Zealand
CTCA	computed tomography coronary angiography
cHn	cardiac troponin
cTnI cTnT	cardiac troponin I
	cardiac troponin T
DAPT	dual antiplatelet therapy
DOAC	direct oral anticoagulants
ECG	electrocardiogram
ED	emergency department
EDACS eGFR	Emergency department assessment of chest pain score
	estimated glomerular filtration rate
ESG	Expert steering group
FFR	fractional flow reserve
GPI	glycoprotein IIb/IIla inhibitor
GRACE	Global Registry of Acute Coronary Events
GRADE	Grading of recommendations, assessment, development and evaluation
HBR	high bleeding risk
HEART High-STEACS	History, electrocardiogram, age, risk factors, troponin
	High sensitivity troponin in the evaluation of patients with acute coronary syndrome
IHIR	hazard ratio
hs-cTn	high-sensitivity cardiac troponin
IR	international normalised ratio
IRA	infarct-related artery
IRR	incidence rate ratio
	intravenous
IVI	intravascular imaging
IIVUS	intravascular ultrasound
K8	kilogram
LBBB LDL-C	left bundle branch block
	low density lipoprotein cholesterol
LMWH	low molecular weight heparin
	left ventricular
LVEF	left ventricular ejection fraction
LVH	left ventricular hypertrophy
MACE	major adverse cardiovascular events
m8	milligram

表 55
II	myocardial infarction
MINOCA	myocardial infarction with non-obstructive coronary arteries
mL/min	millilitres per minute
mm	millimetre
mmol/L	millimoles per litre
RI	magnetic resonance imaging
MVD	multivessel disease
ng/L	nanograms per litre
NHMRC	National Health and Medical Research Council
NSAIDS	non-steroidal anti-inflammatory medicines
NSTEACS	non-ST-segment elevation acute coronary syndromes
NSTEMI	non-ST-segment elevation myocardial infarction
OAC	oral anticoagulant
OR	odds ratio
	probability
PBS	Pharmaceutical Benefits Scheme
PCI	percutaneous coronary intervention
PET	positron emission tomography
PICOTS	patient/population, intervention, comparison, outcome, time, setting
POC	point-of-care
RCT	randomised controlled trial
IRIR	risk ratio
RSW	respiratory syncytial virus
SaO2	arterial oxygen saturation
SAPT	single antiplatelet therapy
SCAD	spontaneous coronary artery dissection
SPECT	stress/rest single-photon emission computed tomography
SPO2	oxygen saturation
STE	ST-segment elevation
STEACS	ST-segment elevation acute coronary syndromes
STEMI	ST-segment elevation myocardial infarction
TIMI	Thrombolysis in myocardial infarction
tPA	tissue plasminogen activator
UA	unstable angina
UDMI	Universal definition of myocardial infarction
UFHI	unfractionated heparin
UK	United Kingdom
VA-ECMO	venoarterial extracorporeal membrane oxygenation
u8	microgram
Hg/L	microgram per litre

表 56

Chest pain - cardiac	Chest pain due to an underlying cardiac aetiology. Includes classic chest discomfort based on
	quality, location, radiation, and provoking and relieving factors that make it more likely to be of cardiac ischaemic origin.

Chest pain - non-cardiac	Chest pain symptoms likely due to a non-cardiac cause.
Chest pain - possible cardiac	Chest pain symptoms that suggest a cardiac origin.
Coronary artery disease (CAD)	CAD refers to the narrowing and/or blockage of the coronary arteries due to accumulation of plaque (atherosclerosis).
Coronary heart disease	Coronary heart disease refers to heart muscle damage that is caused by CAD, where there is reduced blood flow through the coronary arteries. Coronary heart disease is the major underlying cause of acute coronary syndromes.

Coronary microvascular dysfunction	Epicardial or microvascular endothelial or non-endothelial dysfunction that limits
Heart failure	myocardial perfusion, most often detected as reduced coronary flow reserve. Heart failure is a complex clinical syndrome resulting from any structural or functional impairment of ventricular filling or ejection of blood. The main manifestations of heart failure
Heart failure	Heart failure is a complex clinical syndrome resulting from any structural or functional impairment of ventricular filling or ejection of blood. The main manifestations of heart failure are dyspnoea and fatigue (which may limit exercise tolerance) and fluid retention. These may
Heart failure
Heart failure	lead to pulmonary or splanchnic congestion and/or peripheral oedema.
	There is no single diagnostic test for heart failure; it is largely a clinical diagnosis based on a careful history and physical examination including 12-lead ECG, chest X-ray, transthoracic

	echocardiography and laboratory blood testing. When the diagnosis is unclear following
	initial clinical assessment and an echocardiogram cannot be arranged in a timely fashion, measurement of plasma natriuretic peptide levels is recommended. MI is the irreversible necrosis of heart muscle. A common cause of infarction is deprivation in myocardial oxygen supply due to interruption of blood flow in at least one coronary artery
Myocardial infarction (MI)
Myocardial infarction (MI)
Myocardial infarction (MI)	caused by plaque rupture, erosion, fissure, or coronary dissection.
Myocardial infarction (MI)	bradyarrhythmias, anaemia, hypoxaemia, coronary artery spasm, spontaneous coronary artery dissection (SCAD), coronary embolism, and coronary microvascular dysfunction. Type 3 MI is MI resulting in death when biomarkers are not available. Types 4 and 5 MI relate to percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) respectively
Myocardial infarction (MI)
Myocardial infarction (MI)	and accurate detection of MI is important for initiating and maintaining appropriate therapy. In clinical trials, lack of a uniform MI definition can result in low concurrence between theIn clinical trials, lack of a uniform MI definition can result in low concurrence between the initial clinical and later adjudicated assessments of Ml, which will affect accuracy of primaryinitial clinical and later adjudicated assessments of Ml, which will affect accuracy of primary end points and trial outcomes. Thus, uniform definitions are needed to ensure accurate
Myocardial infarction (MI)	end points and trial outcomes. Thus, uniform definitions are needed to ensure accurate reporting of MI events across clinical trials and registries.
MI - Type 1 as per Fourth UDMI
MI - Type 1 as per Fourth UDMI	Type 1 MI is characterised by atherosclerotic plaque rupture, ulceration, fissure, or erosion with resulting intraluminal thrombus in one or more coronary arteries leading to decreased myocardial blood flow and/or distal embolisation and subsequent myocardial necrosis. The person may have underlying CAD but non-obstructive coronary atherosclerosis or there may
MI - Type 1 as per Fourth UDMI
MI - Type 2 as per Fourth UDMI	person may have underlying CAD but non-obstructive coronary atherosclerosis or there may be no angiographic evidence of CAD. Type 2 MI is myocardial necrosis associated with an imbalance between myocardial oxygen
	Type 2 MI is myocardial necrosis associated with an imbalance between myocardial oxygen supply and demand, and may be associated with hypotension, hypertension, tachy/ bradyarrhythmias, anaemia, hypoxaemia, coronary artery spasm, spontaneous coronary artery dissection (SCAD), coronary embolism, and coronary microvascular dysfunction. Type 3 MI is MI resulting in death when biomarkers are not available.
MI - Type 3 as per Fourth UDMI MI - Type 4 and 5 as per Fourth UDMI
MI - Type 3 as per Fourth UDMI MI - Type 4 and 5 as per Fourth UDMI

表 57
Term	Definition
Myocardial infarction with non- obstructive coronary arteries (MINOCA)
Myocardial infarction with non- obstructive coronary arteries (MINOCA)		The diagnosis of MINOCA is made in people with acute myocardial infarction (AMI) that fulfills all following criteria:
Myocardial infarction with non- obstructive coronary arteries (MINOCA)
Myocardial infarction with non- obstructive coronary arteries (MINOCA)	fulfills all following criteria: 1. AMI (modified from the Fourth universal definition of myocardial infarction criteria [15]): Detection of a rise or fall of cardiac troponin (cTn) with at least one value above the 99th percentile upper reference limit and corroborative clinical evidence of infarction based on
Myocardial infarction with non- obstructive coronary arteries (MINOCA)
Myocardial infarction with non- obstructive coronary arteries (MINOCA)	● symptoms of myocardial ischaemia
Myocardial infarction with non- obstructive coronary arteries (MINOCA)	● new ischaemic electrocardiographic changes
Myocardial infarction with non- obstructive coronary arteries (MINOCA)	· development of pathological Q waves
Myocardial infarction with non- obstructive coronary arteries (MINOCA)	· imaging evidence of new loss of viable myocardium or new regional wall motion ab- normality in a pattern consistent with an ischaemic cause ● identification of a coronary thrombus by angiography or autopsy.

		2. Non-obstructive coronary arteries on angiography, defined as the absence of obstructive disease on angiography (i.e. no coronary artery stenosis ≥ 50%) in any major epicardial

	absence of obstructive disease). This includes people with normal coronary arteries (no angiographic stenosis), mild luminal irregularities (angiographic stenosis

表 58
Term	Definition
Older adults	Adults older than 75 years old.
Pericarditis	Pericarditis is inflammation of the pericardial layers characterised by chest pain,
	electrocardiographic changes, and often pericardial effusion. It is often caused by an
	infectious or non-infectious process but can also be idiopathic.
	Pericarditis usually presents with sharp pleuritic chest pain, which may be improved by
	sitting up or leaning forward, although in many instances such findings are not present. A
	pericardial friction rub may be audible. Widespread STE with PR depression is the
Pulmonary embolism	electrocardiographic hallmark, although changes are non-specific and may be transient. Intravascular migration of a venous thrombus to the pulmonary arterial circulation. It isIntravascular migration of a venous thrombus to the pulmonary arterial circulation. It is diagnosed by a positive pulmonary angiogram, an unequivocally positive helical CT scan, a high-probability ventilation-perfusion scan, or autopsy.

Regional and remote	Based on the Australian Bureau of Statistics Australian Statistical Geography Standard
	(ASGS) Edition 3 Remoteness Structure that categorises areas based on relative access to services. Categories are 'major cities', 'inner regional', 'outer regional', 'remote' and 'very remote'.
Spontaneous coronary artery dissection (SCAD)
Spontaneous coronary artery dissection (SCAD)	Epicardial coronary artery dissection that is not associated with atherosclerosis or trauma and is not iatrogenic. Predominant mechanism of myocardial injury occurring due to SCAD is coronary artery obstruction caused by an intramural hematoma or intimal disruption
	rather than atherosclerotic plaque rupture or intraluminal thrombus.
ST-segment elevation myocardial	STEMI is characterised by the presence of both criteria:
infarction (STEMI)	1. Electrocardiographic evidence of STEMI: new or presumed new ST-segment elevation at the J-point in two contiguous leads with the cut-off point: ≥ 1 mm in all leads other than leads V2-V3 where the following cut off points apply: ≥2 mm in men ≥40 years; ≥2-5
	the J-point in two contiguous leads with the cut-off point: ≥ 1 mm in all leads other than leads V2-V3 where the following cut off points apply: ≥2 mm in men ≥40 years; ≥2-5 mm in men

图示：Acute coronary syndromes Unstable angina Acutemyocardialinfarction(AMl) STEACS\* NSTEACS (ST-segmentelevationacute (Non-ST-segmentelevation acutecoronary syndromes) coronary syndromes) NSTEMI STEMI Unstable angina (Non-ST-segmentelevation myocardial infarction) (ST-segmentelevationmyocardialinfarction) ACOMI# (AMI due to significant epicardial coronary occlusion) AMI duetoacutecoronaryocclusion ·Plaquerupture/erosionwiththrombus ·SCAD ·Coronary embolism ·Vasospasm or microvascular dysfunction AMI due to oxygen supply/demand mismatchwithout acute coronaryocclusion Non-elevatedtroponin Increasing troponin

图示：Acutemyocardialinjurywithsignsand/orsymptomsofischaemia MIwith acute MI due to oxygen supply/demand coronaryocclusion mismatchwithout acutecoronaryocclusion Plaquerupture/erosion Spontaneous coronary Coronary Vasospasmor Withfixed Withoutfixed withthrombus arterydissection embolism microvasculardysfunction obstructiveCAD obstructiveCAD

图示：High Central,squeezing gripping,pressure, tightness,heaviness, exertional/stress-related, retrosternal,radiation toarms,neckorjaw Left-sided,aching,dull Probability ofischaemia Stabbing Right-sided,burning, ripping,tearing Sharp,shifting,fleeting, pleuritic,positional Low

图示：9gthpercentile,males 9gthpercentileclinical decisionvalues 99thpercentile,overall Malecut-offs>overallcut-offs>femalecut-offs 9gthpercentile,females Themeansignal atwhich5%of thefrequencydistributionis belowthelimitofblank(i.e.95%confidencethatcTnispresent Limitofdetection in the sample). 50/0

图示：Clinical interpretation of high-sensitivity cardiac troponin Serial testing forsuspected Acs If any elevated troponin value -increased above upper reference limit:>9gth sex-specific percentile Step 1: Identify significant change in serial testing? yes NO Troponinlevel stable Step2:Identifyevidenceofacutemyocardialischaemia? Myocardial infarction Yes 20 Step3:Identifycauseofmyocardialischaemia? Evidence of acute Clinical context and coronaryocclusion mechanisms for oxygen demand and supply imbalancewithout coronaryocclusion MI with acute coronary MI due to oxygen Acutemyocardial Chronic myocardial occlusion supply/demand injury injury mismatchwithout acute Examples Examples Examples coronaryocclusion ·Plaquerupture/erosion ·Acute heart failure Structuralheartdisease SCAD Examples ·Myocarditis ·Chronic kidney disease Coronaryembolism Withfixedobstructive Vasospasm/ CAD microvascular Without fixed obstructive dysfunction CAD

图示：Acute myocardial infarction Chronic myocardial injury 99thpercentileURL Veryearly Early Later Verylate sampling sampling sampling sampling Time from onset of symptoms (hours)

图示：PresentationconsistentwithsuspectedACS Perform12-leadECG ECGfindingsofACOMIor Yes Manageaccordingto high-risk ECG findings Section3Hospitalcare (Section 2.2) andreperfusion 20 LowriskforAMland UseCDP 30-dayMACE High-sensitivitytroponin-based CDP (Section 2.4.1.1) IntermediateriskforAMI and 30-day MACE Cr Clinicalriskscore-basedCDP (Section 2.4.1.2) HighriskforAMl and 30-dayMACE

图示：PresentationconsistentwithsuspectedAcs and Normal ECG or absence of ECG patterns associated with ACO or high-risk ECG features O-hour<A# Otherresults O-hour>D# or 0-hour<B#and△0/2-hour<C# △ 0/2-hour >E# \*Onset of symptoms ≥2 hours LOWrisk INTERMEDIATErisk HIGH risk Bothvalues Eithervalue ≤ sex-specific > sex-specific 99th percentile 99th percentile Discharge Further evaluation of long- Admitforfurther termriskasperAustralian evaluationandtreatment CVDRiskGuideline Further testing asoutpatient recommended Footnote:AdaptationforserialsamplingneededforO/1-hourstrategy.

图示：Symptom FMCSTEMI onset diagnosis AimFMC-to-wire PCl centre Primary PCI crossingtime<60mins OR Immediate AimFMC-to-wire YES transferto Primary PCI crossing<90mins Pathways and PClcentre decisions in CanPCIbe reperfusion Ems or performed Early transfer non-PCI within for coronary centre YES 120mins? angiography between Immediate Fibrinolysis 2O 2-24 hours fibrinolysis successful? Immediate AimFMC-to-needle transferfor time≤30mins rescuePCI Ifcardiogenicshock,immediatetransfertoPClcentrewherepossible Tine delays in Patient reperfusion delay Systemdelay Total ischaemic time

图示：NSTEACS Very high risk based on haemodynamic High risk on hs-cTn algorithms instability/shock: Dynamic ST segment or Life-threatening arrhythmias Non-high riskpeoplein T wave changes Mechanical complicationsofMI whominvasivestrategyischosen Transient ST elevation Ongoing symptoms with ECG changes GRACEscore>140 RecurrentSTelevation Invasive strategy Immediate Early invasive strategy with intent to perform invasive strategy within24hrs revascularisationbefore hospital discharge

图示：PeoplewithACSwithsuccessfulPCloftheIRA withangiographicstenosisinatleastonenon-IRA (vessel ≥2.25 mm) Cardiogenic shock STEMI NSTEACS DonotperformroutinePCl of the Performcomplete Consider complete non-IRA at the index procedure revascularisation.Early (at time revascularisation, either at ofindexprocedure orwithin index procedure or staged. 19days)PCIofthenon-IRAis Considerfunctionalinvasive superiortolaterstagedPCl testing (e.g. FFR) in intermediate(50-70%) Staged complete angiographiclesions revascularisation

图示：Commence all people with AcS on DAPT regardless of revascularisation strategy Aspirin+potentP2Y12inhibitor (ticagrelororprasugrel\*) Lowischaemicand/or High ischaemic and/or Persistinghighischaemic high bleeding risk lowbleeding risk and low bleeding risk 1-3 months OR Durationof de-escalation 6-12months >12 months DAPT after 1month Long termsingleantiplatelettherapy Ticagrelor#orclopidogrelpreferredoveraspirin

图示：TimefromAcs Default antiplatelet Antiplateletstrategyforpeople strategy athighischaemicrisk DOAC+DAPT# DOAC+DAPT# Upto1week Up to 1 month DOAC+SAPT\* 6months DOAC+SAPT\* DOAC+ DOACalone SAPT\* 12months Beyond12months DOACalone

引用 / 出处

2025 NHFA／CSANZ临床指南：急性冠脉综合征的诊断和管理. 2025.

2025 NHFA／CSANZ临床指 南：急性冠脉综合征的诊断和管理

National Heart Foundation of Australia & Cardiac Society of Australia and New Zealand: Comprehensive Australian Clinical Guideline for Diagnosing and Managing Acute Coronary Syndromes 2025

Contents

Disclaimer

Intended use

Liability limitation

(continued).

(continued).

Introduction

Purpose

Scope

Intended Audience

What ’ s New in this Guideline?

Key changes in this guideline

Assessment and diagnosis

Hospital care and reperfusion

(continued).

Recovery and secondary prevention

The Guideline Update Process

Development of Recommendations and Using this Guideline

Table 1 GRADE de ﬁ nitions.

Con ﬂ icts of Interest

1. Preamble

1.1. Impact of ACS in Australia

1.2. De ﬁ nitions and Terminology

1.2.2. Revised de ﬁ nition of myocardial infarction

1.2.4. De ﬁ nition of unstable angina

1.2.5. Myocardial infarction with non-obstructive coronary arteries

1.3. Shared Decision Making

1.4. Collaborative Approaches to Care for First Nations Peoples

2. Assessment and Diagnosis

2.1. Assessment of People with Suspected ACS

2.1.1. Initial assessment summary

2.1.2. History of the presenting complaint

Practice points

Women

Older adults

Factors associated with atherosclerosis [ 48 , 49 ] :

Selected additional risk factors for atherosclerosis (for full details refer to www.cvdcheck.org.au [ 49 ] :

Factors associated with SCAD [ 50 , 51 ] :

Factors associated with coronary embolism [ 52 ] :

Factors associated with coronary vasospasm [ 53 – 55 ] :

Table 3. Continued

Factors associated with coronary microvascular dysfunction

Factors associated with oxygen supply/demand imbalance ( $'+/-$ atherosclerosis) [ 15 ] :

First Nations peoples

2.2. Initial ECG Assessment

Evidence supporting the recommendations

2.2.1. ECG ﬁ ndings of acute coronary occlusion myocardial infarction

Recognised ECG patterns of acute coronary occlusion myocardial infarction

2.2.2. High-risk ECG ﬁ ndings

2.2.3. Other signs of myocardial ischaemia on ECG

Computer-assisted ECG interpretation

2.2.4. Continuous ECG monitoring

Practice points

Table 5 High-risk clinical features for people with suspected ACS requiring ongoing ECG monitoring.

2.2.5. Future direction

2.3. Biomarkers

Evidence supporting the recommendations

2.3.1. Analytic properties of cardiac troponin assays

2.3.2. Point-of-care troponin assays

2.3.3. Clinical interpretation of troponin values

2.3.4. Time from onset of coronary occlusion vs. symptom onset

Differences between troponin T and I assays

Non-MI causes of troponin elevation

Renal disease

Other biomarkers

2.4. Risk Assessment and Clinical Decision Pathways for Suspected ACS

Evidence supporting the recommendations

2.4.1. Clinical decision pathways Risk strati ﬁ cation

2.4.1.1. High-sensitivity troponin-based clinical decision pathways

Single high-sensitivity cardiac troponin measurements

0/1-, and 0/2-hour strategies

High-STEACS algorithm

2.4.1.2. Clinical score-based clinical decision pathways Sites using contemporary cTn assays

2.4.2. Implementing a clinical decision pathway for suspected ACS

Practice points

Women

Older adults

First Nations peoples

2025 NHFA／CSANZ临床指南：急性冠脉综合征的诊断和管理