2025 AHA科学声明：老年人冠状动脉血运重建术

Figure 1. Projected growth of the older adult population (≥65 years) along with the projected growth of revascularization procedures in the older adult population from 2020 to 2060 in the United States.

The blue solid line indicates the projected US population ≥65 years of age based on US Census Bureau data. The red dashed line shows an estimated percutaneous coronary intervention (PCI) usage multiplier, which reflects the relative increase in demand for PCI procedures compared with the baseline year 2020. This multiplier accounts for both demographic aging and projected procedural utilization trends. The PCI usage multiplier is an extrapolated index, assuming proportional growth in procedure volume in response to population aging and comorbidity burden. Adapted from US Census Bureau data (https://www.census.gov/library/stories/2023/05/2020-census-united-states-older-population-grew.html).

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 Figure 2. Chronologic versus biologic aging and the various factors that influence the biologic aging process among older adults with cardiovascular disease.

Multiple modifiable factors, including nutrition, physical activity, sleep, stress management, and environmental exposures, have been shown to influence biologic aging and cardiovascular risk. These upstream determinants remain essential targets for promoting healthy aging and may also influence the success of revascularization and recovery in older adults. CVD indicates cardiovascular disease; and UV, ultraviolet.

 nutrient-sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intracellular communication, chronic inflammation, and dysbiosis (Figure 3).$^{4,5}$ These processes are intimately intertwined with small changes in any individual component leading to substantial changes among the other biologic hallmarks of cardiovascular aging. Inflammation, in particular, has been increasingly recognized as playing a central role in the cardiovascular aging process.$^{3}$

As the study of biologic aging has progressed, examination of individuals with premature versus delayed vascular aging has allowed for identification of factors that promote longevity and those that accelerate the aging process. Using these biomarkers, predictors of aging have been developed, including the vascular aging index and frailty indices.$^{6}$ Additional work has ranged from tracking of inflammatory markers to development of an inflammatory aging clock to further hone prediction of inflammation-related CVD morbidity and mortality.$^{7}$ Because the initial changes associated with biologic cardiovascular aging begin at the cellular level, early identification of physiologic versus pathologic aging as both challenging and of the utmost importance. Furthermore, cardiovascular risk factors, such as uncontrolled hypertension or diabetes, are often associated with an increased inflammatory state beyond that related to chronologic age,$^{8}$ and risk factor modification on a macroscopic level remains a key component of preventive care for CVD.

 # ATYPICAL PRESENTATIONS OF ISCHEMIA IN OLDER ADULTS

The clinical presentation of ischemia in older adults of ten diverges from classic descriptions.$^{1}$ Compared with younger patients, older adults are more likely to present with dyspnea, fatigue, syncope, confusion, or functional decline, and less likely to report chest pain.$^{1}$ These atypical symptoms may delay diagnosis and contribute to underrecognition of ACS, particularly in the setting of cognitive impairment or frailty.$^{1}$ Clinicians should maintain a high index of suspicion and consider early objective testing or consultation when nonspecific symptoms occur in patients with elevated cardiovascular risk.$^{3}$

INTRODUCING GERIATRIC CONCEPTS: A FOUNDATION FOR CARDIOVASCULAR DECISION-MAKING

Older adults age heterogeneously and often have different physiologic profiles at the same chronologic age, resulting in differential risk, recovery, and survival.$^{1}$ For the interventionalist, it is important to consider the physiologic changes that occur with aging and the resultant geriatrics syndromes. Although not all geriatric syndromes are directly relevant to the catheterization laboratory, they may influence decisions before and after the procedure. The framework of the 5Ms of Geriatrics,$^{9}$ shown

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 Figure 3. The 12 hallmarks of aging.

in Table 1, can be useful to recall the many aspects of aging that are relevant to the interventional cardiologist.

Matters Most

Recognition of what matters most is particularly important in the context of revascularization procedures. In a study of patients undergoing transcatheter aortic valve replacement (TAVR) at 52 of 73 centers in California and Washington, the default at most institutions was to re-scind a do-not-resuscitate status, reverting to full code status rather than considering previously agreed-upon patient goals.$^{10}$ However, this may not align with goals of

care for which a palliative approach to a given procedure, or even limited resuscitation goals, may be appropriate. Code status discussions, including do-not-resuscitate and do-not-intubate preferences, are essential but must be approached with sensitivity to clinical context.$^{11}$ Whereas some institutions may temporarily modify code status (eg, do-not-resuscitate reversal) during high-risk interventions to manage reversible complications, this practice aims to optimize procedural outcomes, not override patient preferences.$^{11}$ Do-not-resuscitate or do-not-intubate decisions are dynamic and frequently reevaluated, particularly when patients face acute cardiovascular events.$^{11}$

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Table 1. The 5Ms of Geriatrics: A Framework to Address Key Aspects of Aging Relevant to Cardiovascular Procedural Decision-Making, Including the Catheterization Laboratory and Operating Room

|5Ms of Geriatrics*|Examples|Relevance in the catheterization laboratory| |---|---|---| |Matters Most|Goals and values|Procedures under DNR status Options for limited resuscitation| |Medications|Changes in pharmacokinetics, pharmacodynamics, hepatic and renal function with aging Polypharmacy|Absorption and bioavailability Drug-drug interactions Consider lower doses, slower titration Bleeding risks| |Mind|Cognition (eg, mild cognitive impairment, dementia) Delirium (eg, hyperactive, hypoactive, mixed) Mood (eg, anxiety, depression)|Baseline cognition, need for HCP involvement in consent Risk of delirium because of the procedure, pain, medications Postprocedure mental health| |Mobility|Disability Functional status (eg, IADL, BADL) Falls Sarcopenia|Baseline function and independence may predict outcomes and recovery Reduced muscle mass can impair mobility and recovery Falls and bleeding risk for DAPT considerations| |Multicomplexity|Frailty Multimorbidity, competing chronic conditions Aging physiology (eg, renal function, sensory impairment) Social environment, caregiver stress|Baseline frailty may predict outcomes and recovery Interaction of dominant diseases (eg, pulmonary disease, renal disease) Increased bleeding risk Contrast-induced nephropathy|

BADL indicates basic activities of daily living; DAPT, dual antiplatelet therapy; DNR, do not resuscitate; HCP, health care proxy or health care provider; and IADL, instrumental activities of daily living.

*Geriatric syndromes and clinical implications.

In-hospital mortality as a singular quality metric may not fully capture patient-centered outcomes in older adults, and institutions must balance transparency in reporting with individualized care planning.$^{11}$ Metrics such as 30-day mortality and readmission rates remain the standard for public reporting and quality care standards, but may inadequately capture outcomes relevant to older adults.$^{12}$ Patient-centered outcomes, such as days alive and out-of-hospital functional recovery, should be considered by clinicians when evaluating efficacy of revascularization procedures.$^{12,13}$ A patient- and caregiver-centered discussion on what matters most can help guide the clinician. Decision frameworks, such as the GOOD framework (goals, options, opinions, documentation of the preferred decision)$^{14}$ and the consider, listen, decide framework for CAD,$^{15,16}$ can be useful to guide the complex decision-making process needed to ensure that goals align with care. Tools such as ePrognosis.com can help clinicians understand remaining life expectancy and how a particular revascularization option may or may not fit into that timeline. A palliative approach may be appropriate to alleviate symptoms even if there are competing dominant diseases, such as end-stage renal disease or advanced pulmonary disease.

Medications

Multiple physiologic changes occur with aging that can influence medication effects. This includes changes in

 weight, muscle, and fat mass, affecting drug absorption, pharmacokinetics, and pharmacodynamics, and physiologic changes in hepatic and renal function, affecting first-pass metabolism, bioavailability, and drug clearance.$^{17}$ In addition, chronic kidney injury may be underestimated due to inaccurate calculations using common renal equations that were developed in younger populations.$^{18}$ These changes can lead to increased or decreased drug efficacy, as well as increased risk of adverse events and side effects in older adults, such as bleeding. Older adults with CAD frequently experience polypharmacy, which increases the risk of adverse drug events, drug-drug interactions, and medication nonadherence. Clinicians should regularly review medications for deprescribing opportunities and minimize regimen complexity when feasible. A more detailed discussion of pharmacologic management, including P2Y12 inhibitors, anticoagulants, and the nuances of dual versus triple therapy in patients with atrial fibrillation and coronary disease, is provided later in this article (see Pharmacotherapy in Patients Undergoing Coronary Revascularization).$^{19}$ Strategies that lower bleeding risk may be considered.$^{1}$

Mind

Some cognitive changes, such as slowing process-ing speed, are a normal part of physiologic aging—mild cognitive impairment and dementia are not, but both are increasingly common at older ages and remain

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underdiagnosed.$^{20}$ Before a procedure, awareness of cognitive status is imperative for obtaining adequate consent from a patient or recognizing the need to engage a family member, caregiver, or designated health care proxy.

Recognition of baseline cognitive function can also identify those at risk for delirium. Delirium is an acute change in mental status and attention that is common in older adults who are acutely ill and can be triggered by an invasive procedure, hospitalization, or change in medications.$^{21}$ Delirium is often underdiagnosed, leading to considerable costs and increased risk of postprocedural complications, morbidity, and mortality.$^{22}$ Delirium is a common and serious complication among older adults undergoing invasive procedures, with risks increased in those with preexisting cognitive impairment. Strategies to minimize delirium include maintaining orientation, avoiding unnecessary sedatives, optimizing pain control, encouraging early mobilization, and ensuring sensory aids (eg, glasses, hearing devices) are in use. Moderate dementia should not serve as a blanket exclusion for coronary revascularization, but it is an important factor in procedural risk stratification. Complex interventions associated with high stroke risk or prolonged intensive care may lead to meaningful harm. In contrast, symptom-driven procedures, such as single-vessel percutaneous coronary intervention (PCI), may meaningfully improve quality of life (QoL), even in patients with limited life expectancy. A structured evaluation of goals, expected recovery, and support systems is essential in this context.

Mental health disorders are often undiagnosed in older adults.$^{23}$ Anxiety and depression are common in the older adult population and can lead to an increased risk of complications after an invasive cardiac procedure.$^{24}$ Dementia may not be a reason to withhold care, but represents an opportunity to consider whether a given intervention may help a particular patient at their stage of illness and life.$^{25}$ For example, a 70-year-old individual with moderate dementia without severe disability may have 3 years of additional life expectancy, and not pursuing an invasive strategy may lead to increased harm versus continuing with the procedure.$^{26}$ On the other hand, for those with life expectancy <1 year, it may be appropriate not to pursue a procedure unless there is a potential for immediate relief of symptoms and procedural risks align with goals of care.

Routine cognitive screening in asymptomatic older adults remains an area of active investigation.$^{27}$ However, in high-risk populations, such as those with advanced CVD, previous stroke, or multiple chronic conditions, targeted cognitive assessment may identify impairments relevant to clinical decision-making.$^{27}$ Initial evaluation should include a history from both patient and caregiver, with particular attention to medication adherence, daily functioning, and care coordination.$^{27}$ If concerns regarding cognitive functioning are detected, validated

tools such as the Montreal Cognitive Assessment, Mental State Examination, St Louis University Mental Status Examination, or Ascertain Dementia 8 may be used.$^{27}$ Abnormal findings should prompt laboratory tests (eg, vitamin B₁₂, thyroid-stimulating hormone) and brain imaging to evaluate for reversible causes, and, where indicated, referral to a cognitive specialist. Digital platforms such as the GeriKit app may support this process in cardiology settings.$^{27}$

Mobility

Maximal functional capacity declines with aging at varying rates.$^{28}$ Functional status before an invasive procedure can help predict recovery from an invasive cardiac procedure.$^{29}$ Addition of gait speed, measured over a short distance (eg, 4 to 5 meters),$^{30}$ and other markers of physical function to preoperative risk scores can significantly improve risk prediction.$^{31-33}$ Sarcopenia represents the age-related decline in muscle mass commonly seen in older adults.$^{34,35}$ Sarcopenia may be identified on imaging obtained for procedure planning (eg, psoas muscle) and can help restratify operative risk, including postoperative length of stay.$^{35,36}$ Taken together, each of these aspects contributes to mobility and can alert clinicians to patients at increased risk of peri- and postprocedure risks, including length of stay, falls, and discharge destination, and risk of future recurrent cardiovascular events. Engaging physical therapy and rehabilitation services may help mitigate some of these risks and improve functional status and mobility.$^{37-39}$

Preserving mobility is important for maintaining independence after revascularization. Radial artery access is preferred over femoral access in older adults when feasible, due to lower rates of bleeding and vascular complications. In certain patients, particularly older women with right subclavian tortuosity, a left radial approach may facilitate easier catheter engagement and reduce procedural challenges. Early consultation with physical therapy is encouraged before a procedure (ie, prehabilitation) to establish baseline function, optimize strength, and reduce deconditioning, and after the procedure to support recovery, prevent functional decline, and facilitate discharge planning.

Multicomplexity

The concept of multicomplexity arises when multimorbidity is complicated by polypharmacy or other geriatric risks, including frailty, cognitive impairment, functional decline, or disability. Multimorbidity refers to the co- occurrence of ≥2 chronic conditions and is prevalent in older adults with CAD. Frailty, by contrast, is a distinct bi-ologic syndrome reflecting reduced physiologic reserve and increased vulnerability to stressors, independent of comorbidity burden. Both contribute to procedural risk,

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but frailty is a particularly strong predictor of poor functional recovery, prolonged hospitalization, and death. When a frailty score is calculated using tools such as the Essential Frailty Toolset or Physical Frailty Phenotype, clinicians should use these data to refine risk stratification, inform shared decision-making, and set realistic expectations for postprocedural recovery and support needs.

Older adults often have multiple conditions in addition to heart disease, evidenced by high rates of multi-morbidity (≥2 chronic conditions).$^{40}$ This is often a result of the normal changes in physiology that occur in every system, predisposing to multimorbidity and increasing the complexity of cardiovascular care.$^{41}$ The multiple changes that occur in each body system also contribute to frailty, a syndrome of vulnerability common in older adults that increases the risk of a poor outcome after a stressor event, such as MI.$^{42}$ Frailty can be identified by counting the number of deficits accumulated across body systems (eg, cognitive, functional, medical, nutrition$^{43}$) and is highly associated with CVD.$^{44}$ Alternative assessments for frailty range from the 5-item physical phenotype (encompassing gait speed, strength, weakness, weight loss, and physical activity) to the 9-level clinical frailty scale capturing functional status over the previous 2 weeks.$^{45,46}$ Tools such as Frailty.com can help clinicians identify frailty assessments for any clinical setting.$^{47}$ Frailty, regardless of how it is measured, is predictive of cardiovascular events and increased risk after an invasive procedure.$^{48}$

PROCEDURAL ASSESSMENT AND RISK EVALUATION

Older adults have greater periprocedural risks than do younger patients when undergoing coronary artery revascularization, and require a comprehensive preprocedural risk assessment to inform periprocedural planning, preventive measures, and shared decision-making with patients and their families.$^{2,15,49-51}$ The traditional approach to preprocedural risk assessment includes an assessment of anatomic or technical risks, clinical considerations including comorbid conditions, and hemodynamic status. More recently, leaders in geriatric cardiology have called for the addition of a fourth pillar of risk to be added to the risk stratification paradigm in older adults being considered for coronary artery revascularization: geriatric syndromes (Table 2).$^{2,51}$ We briefly review the 4 pillars of risk assessment for older adults undergoing coronary artery revascularization in Figure 4.

Clinical Risk Assessment

Variably described as the cardiovascular risk assessment, most of the same demographic, clinical, and diagnostic

testing characteristics that predict the risk of coronary artery revascularization in younger populations extend to older adults.$^{3}$ Given the greater burden of comorbidities and the prominent standing of chronologic age as a driver of procedural risk in existing risk models, older adults are expected to have greater periprocedural risks than younger populations on the basis of most commonly available clinical risks.$^{2}$ Validated cardiovascular risk scores such as GRACE (Global Registry of Acute Coronary Events) and TIMI (Thrombolysis In Myocardial Infarction) can provide prognostic information in younger populations being considered for revascularization, but most older adults qualify as high risk under these models, limiting their discriminative utility in that population. Chronologic age remains a strong predictor of short- and long-term outcomes after PCI and is included in the National Cardiovascular Data Registry CathPCI and TVT (Transcatheter Valve Therapy) risk models.$^{3}$ However, reliance on chronologic age alone may misrepresent risk in older adults due to wide heterogeneity in biologic aging.$^{3}$ Emerging evidence supports the integration of geriatric domains—such as frailty, cognition, and functional independence—as complementary modifiers to improve prognostic accuracy and inform clinical decisions in this population.$^{51}$ The CRUSADE score (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the ACC/AHA Guidelines?) is predictive of major bleeding—a crucial outcome in older adults and a strong risk factor for other adverse outcomes.$^{52}$ Perhaps the strongest predictive models for in-hospital death for older adults undergoing PCI are derived from the National Cardiovascular Data Registry, which combines demographic, clinical, and diagnostic predictors with some of the hemodynamic, anatomic, and procedural characteristics described in the following, with excellent performance.$^{53,54}$ For individuals undergoing cardiac surgery, the original EuroSCORE and subsequent updated versions similarly use patient, clinical, and procedural factors to provide accurate prediction of early death after surgery.$^{55,56}$ Future models that take into account more geriatric-specific predictors and outcomes will be necessary to optimize risk stratification in the older adult population being considered for revascularization.

Hemodynamic Risk

Hemodynamic status is a major driver of periprocedural risk across the age spectrum.$^{57}$ Older adults tend to have more advanced disease at the time of presentation and a higher prevalence of comorbidities, such as valvular heart disease and heart failure, that present more complex physiologic challenges. The mortality rate of older adults presenting with acute MI and cardiogenic shock surpasses 40% in those undergoing revascularization and 50% in those who do not.$^{58-63}$ Cardiac arrest at presentation,$^{64}$ acute heart failure,$^{65}$ severe valvular disease,$^{66}$ electrical

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Table 2. Geriatric Syndromes and Their Impact on Coronary Heart Disease Prevalence, Prognosis, and Management

|Geriatric syndrome|Diagnosis and prevalence|Prognosis|Disease management| |---|---|---|---| |Multimorbidity|≥2 chronic conditions (cardiac or noncardiac) that are active simultaneously Prevalence: 63% of adults 65-74 y, 77% of adults 75-84 y, 83% of adults ≥85 y|↑ Short- and long-term prognostic risks attributable to CVD and uncontrolled CVD and non-CVD risk factors|Confounds customary CVD symptoms and signs Multiple diseases and clinicians often result in desynchronized or contradictory aspects of care † Likelihood that patients will experience high therapeutic burden| |Frailty|State of vulnerability relating to diminished physiologic reserve across multiple body systems Multiple definitions; 2 leading theories: physical phenotype and accumulation of deficits Prevalence: 10%-60% of older adults, higher in those with greater CVD burden; depends on measurement tool and cutoff chosen to define frailty|↑ Risk from CVD and medical, device, percutaneous catheter, and surgical therapies used to treat CVD ↑ Risks, disability, falls, rehospitalization, poor quality of life, death|Guidelines-based therapy and procedures commonly overlook the effect of frailty on recommendations Intensive care, bed rest, and functional decrements associated with many conventional therapies can exacerbate frailty and functional decline Nutrition and exercise may help mitigate frailty and risks of frailty| |Cognitive decline|Mild cognitive impairment: ↓ cognitive function without loss of function Prevalence estimates vary with population and methods, but increases with age, generally in the range of 2%-5% (60-65 y) to >20%-40% (≥90 y) Dementia: severe memory loss, loss of executive function, and other cognitive abilities that interferes with daily life and loss of functional independence Prevalence increases with age, from >≈50% of people 71-79 y to 35%-40% of those ≥90 y|↓ Independence ↓ Adherence ↓ Shared decision-making ↓ Quality of life ↑ Hospitalization ↑ Death|Often confounds assessments of symptoms, present illness, and medical history Often confounds adherence Does not negate the potential value of therapeutic intervention, but affects the decision and implementation process| |Delirium|Acute disturbance in cognition, attention, and consciousness or perception, with fluctuating course Can manifest as agitated state (hyperactive), quiet and withdrawn (hypoactive), or mixed High prevalence (≤30%-60%) in older adults who are hospitalized|↑ Length of stay ↑ Rehospitalization ↑ Functional decline ↑ Falls ↑ Long-term care ↑ Death|Prevention of delirium should take priority by optimizing the environment to increase orientation, avoid sedation, reduce medications, reduce and manage pain, avoid constipation and urinary retention: Predisposing risks include cognitive deficits, sensory limitations, and disorienting medications Treat by optimizing environment to increase orientation, avoid sedation, reduce medications, reduce pain, optimize bowel and bladder function, maintain circadian rhythm and interpersonal interactions| |Polypharmacy|Use of ≥5 concurrent medications; ≥10 is considered hyperpolypharmacy May have unintended interactive effects (not required for definition) 40% of older adults take ≥5 medications|↑ Adverse events (errors and drug interactions) ↑ Falls ↑ Rehospitalizations ↑ Death|↑ Medication errors ↑ Drug-drug and drug-body interactions ↓ Adherence common Under- and overtreatment both commonly occur Consider deprescribing, with the goal to optimize prescribing, even if ≥5 drugs| |Disability|Inability to care for oneself or to manage one's own lived environment independently|↑ Risk of progressive functional and cognitive decline ↓ Self-reliance and self-efficacy ↓ Self-reliance and self-efficacy ↑ Long-term care ↑ Death|Conventional care for CVD often contributes to a cycle of progressive disability, which highlights rationale for shared decision-making for each aspect of therapy Conventional care for acute coronary syndrome (including pharmacotherapy, procedural care, and bed rest) can result in temporary immobility, delirium, and disturbance in sleep pattern, and increase risk of loss of independence Suboptimal transitions are common contributors to disability (leg, hospital to home, hospital to postacute care, or hospital to home if support is inadequate or patient education has been deficient)| |Sensory loss|Vision, hearing, taste, touch deficits common|↑ Risk of progressive functional and cognitive decline ↓ Self-reliance and self-efficacy ↑ Long-term care ↑ Death|Same as disability|

CVD indicates cardiovascular disease.

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 Figure 4. The 4 pillars of risk in older adults presenting for coronary revascularization procedures.

CABG indicates coronary artery bypass grafting; COR, Class of Recommendation; DAPT, dual antiplatelet therapy; GRACE, Global Registry of Acute Coronary Events; HFrEF, heart failure with reduced ejection fraction; LIMA, left internal mammary artery; LOE, Level of Evidence; LVEF, left ventricular ejection fraction; NR, nonrandomized; PCI, percutaneous coronary intervention; STS PROM, Society of Thoracic Surgeons Predicted Risk of Mortality; and TIMI, Thrombolysis in Myocardial Infarction.

instability,$^{67}$ and mechanical complications$^{68}$ all portend a poor prognosis and high risk for both subsequent complications and death. In the National Cardiovascular Data

Registry risk model for in-hospital death, cardiogenic shock and salvage PCI are the strongest predictors of risk.$^{53,54}$

CLUNICAL STATELOGUES AND GUIDE ALDEUMES

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Anatomic and Technical Risk

A nuanced assessment of the anatomic burden of coronary disease, procedural considerations, and technical challenges is a core component of the overall risk stratification of older adults being considered for revascularization. Older adults more frequently present with advanced coronary disease including high-risk anatomic features such as left main disease, multivessel disease, chronic total occlusions, and more diffuse disease.$^{53,54,69,70}$ Risk scores, such as the SYNTAX score (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery), have been developed to quantify the complexity of CAD and guide the optimal revascularization approach.$^{71}$ Severe calcification is more prevalent in the geriatric population$^{72}$ and can introduce technical challenges for delivery of equipment, stent expansion, and complications from more aggressive techniques to modify the calcium.$^{73}$ Calcium modification therapies such as atherectomy may have higher risk for complications and death in older adults than in younger patients. For calcified lesions, plaque modification techniques using orbital or rotational atherectomy, and more recently, intravascular lithotripsy, which has demonstrated improved safety and ease of use compared with atherectomy in older adults, may be required. Vascular tortuosity is more common in older adults, which presents challenges for vascular access and successful PCI.$^{74,75}$ In patients who require mechanical circulatory support, concurrent peripheral arterial disease may limit access site options and increase the risk for complications.$^{76}$

Geriatric Risk

A recent expert panel called for the addition of a fourth pillar for the comprehensive risk assessment of older adults: integration of geriatric syndromes (Figure 4). This encompasses geriatric syndromes across multiple different domains, including physical function, mind and emotion, medical, and social environment.$^{77}$ Geriatric syndromes have been strongly associated with higher risk for adverse outcomes. For example, frailty, which is highly prevalent among older adults undergoing PCI,$^{78}$ is associated with poor outcomes after both PCI and coronary artery bypass grafting (CABG),$^{79-81}$ including triple the odds of in-hospital death.$^{53}$ Biologic age as quantified by deficits and functional impairments improves upon chronologic age in the prediction of death.$^{82}$ Thus, a comprehensive geriatric risk assessment is recommended in addition to the clinical, hemodynamic, anatomic, and technical risk assessments required to inform a shared decision around revascularization.$^{51}$ At a minimum, this should include assessments of function, activities of daily living, instrumental activities of daily living, and goals of care, but may include further targeted geriatric measures of multimorbidity, polypharmacy, cognition, delirium, depression, frailty, hearing or vision impairment, mobility, sarcopenia, and social support.$^{51}$ Eliciting the older

patient's health goals and priorities using a validated tool, such as the Patient Priorities Care approach$^{83-89}$; evaluating individual risk tolerance$^{90}$; and implementing a shared-decision framework should all be considered to facilitate effective person-centered care.$^{15,16,91}$

REVASCULARIZATION IN OLDER ADULTS

Revascularization in ST-Segment-Elevation MI

Reperfusion Strategies

In the United States, ≈780000 people experience an ACS each year, 30% of whom have ST-segment-elevation MI (STEMI).$^{92}$ Age is a major risk factor for CVD and 30% of all patients admitted with STEMI are ≥75 years of age.$^{93}$ Whereas the overall incidence of STEMI in the United States has decreased over the past few decades, the aging of the population has resulted in an increased proportion of patients with STEMI among older adults.$^{94}$ Using the National Inpatient Sample to identify hospitalizations for PCI in patients ≥90 years of age from 2003 to 2014, it was determined that the representation of nonagenarians among all PCI hospitalizations increased more than 2-fold (0.6% to 1.4; P <0.001), and the proportion of PCIs performed for STEMI increased from 23.1% to 30.9% ($P_{trend} <0.001$).$^{94}$ It is reasonable to anticipate the continuation of this trend is estimated that by 2050, adults >75 years of age will number ≈46 million, representing 11.5% of the US population (Figure 1).$^{95,96}$

Age is a well-established risk factor for the development of CAD, as well as for increased risk of morbidity and mortality in patients with STEMI. Among 5745 patients participating in the APEX-AMI trial (Assessment of Pexelizumab in Acute Myocardial Infarction) from July 13, 2004, through May 11, 2006, those >75 years of age (n=977) were significantly less likely to achieve angiographic success after primary PCI (pPCI), had less frequent ST-segment resolution, and had higher rates of in-hospital bleeding, electrical, and mechanical complications when compared with patients <65 years of age.

13, 2004, through May 11, 2006, those >75 years of age (n=977) were significantly less likely to achieve angiographic success after primary PCI (pPCI), had less frequent ST-segment resolution, and had higher rates of in-hospital bleeding, electrical, and mechanical complications when compared with patients <65 years of age. In multivariate analysis, age was the strongest predictor of death at 90 days (hazard ratio, 2.07 per 10-year increase [95% CI, 1.84-2.33]), and patients >75 years of age were almost 6 times more likely to experience death within 90 days (5.64 [4.20-7.56]; $P<0.001$).$^{97}$ Older patients are more likely to present with atypical symptoms, longer time from symptom onset to first medical contact, nondiagnostic ECG findings, and preexisting medical conditions that adversely affect tolerance of the acute cardiac event and related medical interventions.$^{193,97,98}$ Complicating matters further, studies have consistently demonstrated that older patients are less likely to receive reperfusion and other guideline-directed medical therapies.$^{99}$ Studies have demonstrated a much higher prevalence of cardiogenic shock among elderly patients with STEMI compared with younger patients,

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and elderly patients with cardiogenic shock have a much lower chance of survival.$^{100}$ In a European cohort, the prevalence of cardiogenic shock in patients with STEMI was >2-fold higher among patients ≥75 years of age compared with younger patients (10.8% versus 3.9%; $P<0.0001$).$^{101}$

In patients with STEMI complicated by cardiogenic shock, early revascularization remains the standard of care. Mechanical circulatory support, including microaxial flow pumps, may be used to stabilize hemodynamics during revascularization. However, recent secondary analysis of the DanGer Shock trial (Danish-German Cardiogenic Shock) demonstrated that the mortality benefit of microaxial flow pumps was limited to patients <77 years of age.102 Among those ≥77 years of age, microaxial flow pumps were associated with a greater number of deaths compared with standard care, but this subgroup analysis was not statistically powered for definitive conclusions ($P_{interaction} = 0.028$).102 These findings raise important considerations about physiologic reserve, procedural complications, and the individualized use of mechanical circulatory support in older patients with STEMI-related shock.102

American and European society guidelines recommend pPCI as the preferred reperfusion strategy in all patients with acute STEMI with symptom onset to first medical contact <12 hours, regardless of age, when presenting to a facility with pPCI capabilities and door-to-balloon time <90 minutes or anticipated transfer to reperfusion time <120 minutes (Class 1; Level of Evidence A).$^{103,104}$ Clinical trial data are limited, but a summary of available evidence supports the preferred use of pPCI over fibrinolysis in older patients, with net improvement in mortality, disabling stroke, and reinfarction rates.$^{105}$ Over recent decades, observational data from national registries have consistently demonstrated that increased use of pPCI has led to improved survival, with older patients receiving particular benefit.$^{106-108}$ Even among nonagenarians, observational studies have demonstrated that compared with medical therapy, pPCI is safe and associated with reduced in-hospital and 30-day mortality rates.$^{109,110}$

In patients unable to receive pPCI, it is recommended that older patients should receive fibrinolysis when appropriate.$^{104,111}$ Because the incidence of bleeding complications, especially intracranial hemorrhage, is higher among older patients, some considerations are worth noting. First, the STREAM (Strategic Reperfusion in Elderly Patients Early After Myocardial Infarction) and STREAM-2 clinical trials demonstrated the importance of half-dose fibrinolytic therapy in reducing bleeding complications among patients >75 years of age, and that a strategy of half-dose fibrinolytic therapy in elderly patients presenting within 3 hours of symptom onset and in whom pPCI was not available within 1 hour had similar safety and efficacy compared with pPCI.$^{112,113}$ Second,

clopidogrel should be considered the preferred adjunctive P2Y12 receptor inhibitor in patients receiving fibrinolytic therapy, and patients >75 years of age should receive an initial dose of 75 mg followed by a maintenance dose of 75 mg once daily.$^{104}$ Third, transradial artery access has been proven safe in older patients undergoing pPCI, and should be considered the preferred access site owing to its benefits in lowering the risk of bleeding and vascular complications, acute kidney injury, and perhaps also death in patients with STEMI.$^{114-116}$

Revascularization in Non-ST-Segment-Elevation MI

Evidence from Randomized Trials

Of the 6 randomized clinical trials investigating an invasive strategy in older patients with non-ST-segment-evaluation MI (NSTEMI), 4 showed no benefit of invasive treatment over conservative management on the primary end point, whereas 2 demonstrated reduced recurrent MI and urgent revascularization rates.$^{117-120}$ The Italian Elderly ACS trial (Early Aggressive Versus Initially Conservative Therapy in Elderly Patients With Non-ST-Elevation Acute Coronary Syndrome),$^{117}$ which included patients ≥75 years of age with non-ST-segment-elevation ACS (NSTE-ACS), found that those in the conservative group experienced higher ischemic events during hospitalization, which resulted in higher urgent angiography rates. There was a 20% reduction in death, reinfarction, disability stroke, or rehospitalization rates with the invasive approach, but these results were not statistically significant, because the trial was powered for a 40% difference. In the After Eighty study,$^{121}$ patients ≥80 years of age with NSTEMI or unstable angina had significant benefit from invasive treatment in reducing MI, urgent revascularization, and stroke rates over a median follow-up of 18 months. The MOSCA trial (Invasive vs Conservative Strategies in Non-ST-Elevation Acute Coronary Syndrome and Comorbidities)$^{118}$ suggested fewer events in the invasive group, although statistical significance was not reached.

SENIOR-RITA (A Study to Evaluate the Benefit of Medical Therapy versus Angiography and Stenting in Patients With Heart Attacks),$^{122}$ recently published in The New England Journal of Medicine, randomized patients ≥75 years of age with type 1 NSTEMI to invasive or conservative management. The trial found no clear survival advantage with the invasive strategy, although there was a reduction in rates of recurrent MI and need for revascularization, accompanied by increased bleeding risk.$^{122}$ These findings highlight the complexity of applying invasive strategies in older adults. Observational data, such as from SENIOR-NSTEMI (Invasive versus Noninvasive Management of Older Patients With Non-ST Elevation Myocardial Infarction),$^{123}$ have suggested a survival benefit in patients >80 years of age, but these results are

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limited by potential confounding. An individual patient-data meta-analysis of randomized controlled trials (RCTs) in older patients with NSTE-ACS showed that a routine invasive approach reduced reinfarction and urgent revascularization rates but did not significantly reduce mortality rates.$^{124}$ A more recent meta-analysis that included 5 RCTs and pooled analyses from FIR (FRISC II [Fragmin and Fast Revascularization During Instability in Coronary Artery Disease], ICTUS [Invasive Versus Conservative Treatment in Unstable Coronary Syndromes], and RITA-3 [Intervention Versus Conservative Treatment Strategy in Patients With Unstable Angina or Non-ST Elevation Myocardial Infarction]) also demonstrated that early invasive management in patients ≥75 years of age significantly reduced rates of the composite end point of death or MI, as well as repeat revascularization and MI rates, without increasing bleeding risk (Table 3).$^{124}$ Nonrandomized data from SENIOR-NSTEMI also suggested a survival benefit for patients >80 years of age managed invasively. In an individual patient-data meta-analysis of RCTs in older patients with NSTE-ACS, a routine invasive strategy reduced the risk of reinfarction and urgent revascularization without significantly affecting all-cause

mortality rates or the combined end point of death and MI rates at 1 year.$^{125}$ A recent meta-analysis of 5 RCTs, 1 RCT subgroup (TACTICS-TIMI 18 [Treat Angina With Aggrastat and Determine Cost of Therapy With an Invasive or Conservative Strategy]), and 3 studies derived from age-stratified patient-level pooled analysis (FIR) in patients ≥75 years of age with NSTE-ACS found that an early invasive strategy significantly reduced the composite of death or MI compared with conservative management, along with lower rates of repeat revascularization and MI. This benefit was achieved without increasing bleeding risk (Table 3).$^{124}$ Given the heterogeneity of findings in older adults with NSTEMI, a nuanced approach to invasive management is warranted. Based on available randomized data including SENIOR-RITA and previous meta-analyses, an early invasive strategy may be preferred in patients with recurrent angina, hemodynamic or electrical instability, elevated tropomin, or high-risk anatomy.$^{122,124}$ However, a conservative approach may be appropriate in those with advanced frailty, cognitive impairment, or limited life expectancy, or when the likelihood of benefit is outweighed by procedural risk or patient preference.$^{3}$ Shared decision-making

Table 3. Revascularization Trials Specifically Including Adults ≥75 Years of Age With Acute Coronary Syndrome

|Trial (year)|Study population (age, y)|Randomized intervention|Age included, y|Primary end point|Secondary end points| |---|---|---|---|---|---| |TACTICS-TIMI 18 (2001)|ACS (>75)|Invasive vs conservative|Mean 80|15.9% vs 19.4% for death, MI, and rehospitalization for ACS|Lower mortality and MI rates, especially in elevated troponin group| |FIR (2012)|ACS, recent chest pain, troponin elevation|Invasive vs conservative|Median 76|26.1% vs 34.9% for death, MI, or refractory angina (P=0.007)|Fewer hospitalizations and sustained symptom relief over 5 y; higher bleeding rates| |Italian Elderly ACS (2012)|ACS (>75)|Invasive vs conservative|Mean 80|36% vs 53% for death, MI, stroke, or rehospitalization|Lower recurrence of angina and improved QoL| |After Eighty (2016)|NSTE-ACS (≥80)|Invasive vs conservative|Median 84|40% vs 61% for MI, urgent revascularization, stroke, or rehospitalization for ACS|Improved survival and symptom relief| |MOSCA (2016)|NSTE-ACS, comorbidities|Invasive vs conservative|Mean 80|19.2% vs 39% for death, MI, revascularization for ACS|Fewer recurrent cardiac events, long-term outcomes| |80+ (2020)|NSTE-ACS, ischemic symptoms|Invasive vs conservative|Median 83|36% vs 56% for death, MI, revascularization, stroke, or rehospitalization|Improved symptom management, reduced rehospitalization| |RINCAL (2021)|NSTE-ACS (≥80)|Invasive vs conservative|Median 85|24% vs 34% for death or MI|Improved overall survival and symptom relief| |MOSCA-FRAIL (2023)|NSTE-ACS (≥75)|Invasive vs conservative|Mean 85|Stopped prematurely due to COVID-19; 284 vs 312 d alive out of the hospital|No difference in the co-primary end point of ischemic cardiac events (cardiac death, reinfarction, postdischarge revascularization)| |SENIOR-RITA (2024)|NSTEMI (≥75)|Invasive vs conservative|Median 82|25.6% vs 26.3% for cardiovascular death or nonfatal MI|11.7% vs 15% for nonfatal MI| |FIRE (2024)|ACS (≥75); multivesel CAD|Physiology-guided complete vs culprit-only|Median 81|15.7% vs 21.0% for composite of death, MI, stroke, or revascularization for|Lower death, MI, ischemia-driven revascularization; improved symptom relief and QoL|

ACS indicates acute coronary syndrome; CAD, coronary artery disease; FIR, FRISC II (fragmin and Fast Revascularization During Instability in Coronary Artery Disease); FIRE, Functional Assessment in Elderly MI Patients With Multivessel Disease; MI, myocardial infarction; MOSCA, Comorbilidades en el Síndrome Coronario Agudo; MOSCA-FRAIL, Invasive and Conservative Strategies in Elderly Frail Patients With Non-STEMI; NSTE-ACS, non-ST-segment-elevation acute coronary syndrome; NSTEMI, non–ST-segment-elevation myocardial infarction; OoL, quality of life; RINCAL, Revascularisation or Medical Therapy in Elderly Patients With Acute Anginal Syndromes; SENIOR-RITA, A Study to Evaluate the Benefit of Medical Therapy versus Angiography and Stenting in Patients With Heart Attacks; and TACTICS-TIMI 18, The Angina With Aggrastat and Determines Cost of Therapy With an invasive or Conservative Strategy.

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should incorporate these clinical and geriatric factors to individualize the revascularization strategy.

The recent American College of Cardiology/AHA/ American College of Emergency Physicians/National Association of EMS Physicians/Society for Cardiovascular Angiography & Interventions guidelines for the management of ACS do not include specific recommendations for the care of older adults, which emphasizes the need for geriatric-focused clinical guidance for clinicians in practice.$^{126}$ Thus, whereas evidence shows that an invasive strategy may reduce MI and revascularization rates, its impact on survival in patients ≥75 years of age remains unclear and dependent on patient profile and clinical characteristics, highlighting the need for further studies in this space.$^{1,3}$

Stable Ischemic Heart Disease

Revascularization Versus Medical Therapy

Adults ≥75 years of age have historically been under-represented in randomized trials investigating revascularization for stable ischemic heart disease (SIHD).$^{127,128}$ However, limited randomized evidence exists supporting both PCI and CABG in older adults with SIHD to provide symptomatic and clinical outcome benefits (Table 4). Until recently, the only randomized trial evaluating revascularization versus medical therapy alone that enrolled a large number of older adults was TIME (Trial of Invasive versus Medical Therapy in Elderly Patients), which enrolled 305 patients ≥75 years of age with stable angina on ≥2 antianginal medications from 1996 to 2000.$^{129}$ Participants were randomized to coronary angiography and revascularization or optimal medical therapy. Of the 147 participants who underwent catheterization, 79 received percutaneous transluminal coronary angioplasty and 30 received CABG. At 6 months, an invasive approach with revascularization (PCI or CABG) was associated with a decrease in angina severity and improvement in QoL beyond medical therapy alone; there was also a significant reduction in major adverse cardiac events (MACEs), defined as death, MI, or hospitalization for uncontrolled symptoms or ACS, in the invasive group compared with medical therapy (19% versus 49%; P<0.0001). Of the 282 patients surviving to 6 months, improvements in angina and QoL persisted to 1 year, but there was no longer any significant difference between the treatment arms.$^{130}$ However, the invasive approach remained favorable in comparison with medical therapy alone with regards to MACEs at 1 year (25.5% versus 64.2%; P<0.001), which was driven by significantly higher rates of hospitalization with revascularization in those assigned to the medical treatment arm. A number of landmark trials of PCI versus medical therapy published since TIME—such as DEFER (Deferral versus Performance of PTCA in Patients Without Documented Ischemia),$^{131}$ COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive

Drug Evaluation),$^{132}$ FAME 2 (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation 2),$^{133}$ and ORBITA (Objective Randomised Blinded Investigation With Optimal Medical Therapy of Angioplasty in Stable Angina)$^{134}$—have either not included a large number of participants ≥75 years of age or not published results in that cohort. In 2020, ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) demonstrated no significant difference in a composite MACE outcome between an invasive versus medical therapy strategy in 5179 participants with stable coronary disease and moderate or severe ischemia,$^{135}$ but did find that the invasive strategy was associated with an improvement in symptoms.$^{136}$ ISCH-EMIA included the largest cohort of older adults with SIHD of any revascularization trial, enrolling 665 adults ≥75 years of age and publishing the age-specific results in 2023.$^{137}$ The authors identified a significant interaction by age for the Seattle Angina Questionnaire Summary Score ($P_{interaction} = 0.008$), and older adults tended to have less improvement in angina-related health status with invasive management with consistent improvement in angina frequency.$^{137}$ Age-specific results have yet to be reported for more recent trials evaluating PCI compared with medical therapy in SIHD.$^{138,139}$ Because observational data suggest increased risks of PCI in older adults, future trials providing more definitive evidence for patient-centered benefits of PCI compared with medical therapy are of paramount importance.

PCI Versus CABG in Older Adults

A number of randomized trials evaluating CABG versus PCI for SIHD have included limited samples of older adults. EXCEL (Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) randomized 1905 participants with left main coronary disease of low or intermediate atomic complexity (≈53% with stable angina) to PCI or CABG and included the largest cohort of individuals ≥75 years of age in a CABG trial to date, finding that PCI was noninferior to CABG in terms of MACEs at 3 years.$^{140}$ Results were consistent in the small sample (n=319) of participants ≥75 years of age ($P_{interaction} = 0.12$ for MACEs at 3 years),$^{141}$ The subsequent FREEDOM trial (Future Revascularization Evaluation in Patients With Diabetes Mellitus: Optimal Management of Multivessel Disease) randomized 1900 patients with diabetes and multivessel CAD (≈69% without ACS) to PCI versus CABG, including 190 participants >75 years of age.$^{142,143}$ In FREEDOM, the composite of death from any cause, nonfatal MI, or nonfatal stroke was significantly higher at 5 years with PCI (26.6%) versus CABG (18.7%; P=0.005), as was the all-cause mortality rate at a median follow-up of 7.5 years (CABG 18.3% versus PCI 24.3%; P=0.01). Unlike other CABG versus PCI trials, the FREEDOM authors observed an interaction by age: the benefits from CABG

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Table 4. Revascularization Trials Specifically Including Adults ≥75 Years of Age With Stable Ischemic Heart Disease

|Trial (year)|Study population (sample size, n)|Randomized intervention|Age included, y|Specific results in older adults|Primary end point|Secondary end points| |---|---|---|---|---|---|---| |TIME (2001)|≥75 y with chronic angina with CCSC >2 and ≥2 antianginal drugs|Revascularization (PTCA or CABG) vs medical therapy|Mean 80|All results apply specifically to older adults; all patients included in the trial were ≥75 y|QoL at 6 mo (SF-36) significantly improved with invasive strategy with invasive strategy|All other QoL measures also improved with revascularization at 6 mo; MACEs improved with revascularization at 6 mo (19% vs 49%; P<0.0001)| |COURAGE (2007)|Stable angina or silent ischemia and CAD (>70% stenosis)|PCI with OMT vs OMT alone|Mean ≈62; 24% of participants ≥70; unclear how many participants ≥75|Results specifically for older adult cohort not published|Death and MI at median follow-up of 4.6 y was 19% (PCI) vs 18.5% (OMIT; P=0.62)|No significant differences in composite of death, MI, and stroke, hospitalization for ACS, or MI| |BARI 2D (2009)|Type 2 diabetes and evidence of ischemia|Prompt revascularization (PCI or CABG) vs medical therapy|Mean ≈63; maximum 89.8; 182 participants ≥75|Results for patients ≥75 y not reported; results for patients ≥70 y; effect of revascularization vs medical therapy did not differ by age for death ($P_{interaction}$ =0.99), major cardiovascular events, angina, or health status outcomes; health status improvement was less sustained in older vs younger patients; no difference in patients ≥65 at 5 y in QoL|5-y survival: 88.3% with revascularization vs 87.8% with medical therapy|No difference in rate of freedom from MACEs; no difference in death for the CABG or PCI strata; CABG, but not PCI, associated with fewer MACEs compared with medical therapy| |PRECOMBAT (2011)|Left main CAD; ≈50% stable angina or no symptoms|PCI vs CABG|Mean ≈62; 146 participants ≥70|Included in meta-analysis of older adults (70–89 y) from CABG vs PCI trials including BEST and 24 mo in those >75 y|PCI noninferior to ACEG for MACCE at 2% vs 6.7%); P=0.01 for noninferiority at 1 y|PCI noninferior to ACEG for MACCE at 2 y; composite of death, MI, and stroke similar between PCI (4.4%) and CABG (4.7%) at 2 y| |FAME 2 (2012)|Stable CAD suitable for PCI|PCI vs medical therapy|Mean 63.5; 106 participants ≥75*|Results specifically for older adult cohort not published|Composite of death, MI, or urgent revascularization (trial stopped early): 4.3% (PCI) vs 12.7% (medical therapy); P<0.001|Death or MI did not differ between groups; difference in MACE was driven by difference in urgent revascularization| |FREEDOM (2012, 2019)|Diabetes and multivessel CAD with diameter stenosis ≥70% in ≥2 major epicardial vessels involving 2 separate coronary territories; ≈69% non-ACS|CABG vs PCI|Mean ≈63; 180 patients >75|Benefits from CABG not seen in older patients (>63.3 y; $P_{interaction}$ =0.001); treatment effect appeared consistent for angina frequency improvement with CABG at 12 and 24 mo in those >75 y|Composite of death from any cause, nonfatal MI, or nonfatal stroke was significantly higher at 5 y with PCI (26.6%) vs CABG (18.7%; P=0.005); all-cause death at median follow-up 75 y: CABG 18.3% vs PCI 24.3% (P=0.01)|CABG favored for both MI (P<0001) and death from any cause (P=0.049); stroke more common with CABG (5.2%) vs PCI (2.4%; P=0.03)| |BEST (2015)|Multivessel CAD|PCI vs CABG|294 participants ≥70|Included in meta-analysis of older adults (70–89 y) from CABG vs PCI trials including BEST and SYNAX trials demonstrating CABG was associated with lower risk of all-cause mortality, MI, stroke, or repeat revascularization; consistent point estimate for benefit with CABG in those ≥80 y in meta-analysis|Composite of death, MI, or target vessel revascularization at 2 y was 11% (PCI) vs 7.9% (CABG); P=0.32 for noninferiority|At 4.6-y long-term follow-up, primary end point 15.3% (PCI) vs 10.6% (CABG; P=0.04); higher rates of repeat revascularization and spontaneous MI with PCI vs CABG|

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Table 4. Continued

|Trial (year)|Study population (sample size, n)|Randomized intervention|Age included, y|Specific results in older adults|Primary end point|Secondary end points| |---|---|---|---|---|---|---| |EXCEL (2016)|Left main coronary disease of low or intermediate anatomic complexity (≈53% with stable angina)|PCI vs CABG|Mean ≈66; 319 participants ≥75|Results consistent in the small sample of those ≥75 y ($P_{interaction}^{=0.12}$ for MACE at 3 y)|PCI noninferior to CABG for MACE (death, stroke, or Ml) at 3 y|PCI noninferior to CABG for 30-d MACE and MACE or ischemia-driven revascularization at 3 y| |STICH (2016)|CAD amenable to CABG and HFrEF (EF <35%)|CABG vs medical therapy|Median ≈60; 75 patients up to age 85 were enrolled|308 patients >67 y with median age 72; trend toward attenuated benefit of CABG with increasing age on all-cause mortality ($P_{interaction}^{=0.06}$) but consistent benefit on cardiovascular mortality across all ages|Death at ≈10-y follow-up 58.9% (CABG) vs 66.1% (medical therapy); P=0.02|CABG favored for multiple secondary outcomes: death from cardiovascular causes, HF, and MACE| |NOBLE (2016)|Left main CAD; ≈83% stable angina|CABG vs PCI|Mean ≈66; 622 patients ≥67 (mean age 73) and 77 patients >80|Among older participants, MACCE was higher with PCI (35.7%) vs CABG (22.3%; P=0.0004), driven by higher rates of MI (10.8 vs 3.8%; P=0.0009) and repeat revascularization (19.5 vs 10.0%; P=0.002); significant results were not seen in the younger age group, but there was no significant interaction between age and treatment|5-y MACCE: PCI 28% vs CABG 18%; HR, 1.51 (95% CI 1.13-2.00); P=0.0044|MI: 6% vs 2% ($P=0.0040$); revascularization: 15% vs 10% ($P=0.03$); stroke: 5% vs 2% ($P=0.08$)| |ORBITA (2018)|Stable angina with ≥70% single-vessel stenosis|PCI vs placebo procedure|Mean 66|Results specifically for older adult cohort not published|No significant difference in exercise time between PCI and a placebo procedure|No improvement in CCSC, SAQ, or EQ-5D-5L with PCI| |SYNTAX (2019)|De novo 3-vessel or left main coronary artery disease or both; ≈57% stable angina|PCI vs CABG|Mean ≈65; 575 patients >70 with mean age 75.8 in that group and 94 participants ≥80|Among older participants enrolled, risk of all-cause death or MACCE at 5 y did not differ by age between PCI and CABG; higher risk of MACCE with PCI compared with CABG in younger patients does not extend to older patients|All-cause death at 10 y 28% for PCI vs 24% for CABG (P=0.066)|CABG, compared with PCI, provided a survival benefit in those with 3-vessel disease but not those with left main disease ($P_{interaction}^{=0.02}$) =0.02)| |ORBITA-2 (2023)|Stable angina with ≥1 severe coronary stenosis ≥70% and evidence of ischemia|PCI vs placebo procedure|Mean 64; >85 excluded|Results specifically for older adult cohort not published|Mean angina symptom score was significantly improved at 12-wk follow-up with PCI|Greater freedom from angina and improvements in treadmill exercise time, SAQ, and EQ-5D-5L with PCI compared with placebo procedure| |ISCHEMIA (2020)|Stable coronary disease and moderate or severe ischemia|Invasive vs conservative strategy|Mean 64; 665 adults ≥75 in age subanalysis|$P_{interaction}$ by age 0.008 for SAQ Summary Score; among the 665 individuals ≥75 y in age subanalysis, older adults tended to have less improvement in angina-related health status with invasive management with consistent improvement in angina frequency|MACE for invasive vs conservative: at 6 mo: 5.3% vs 3.4%; at 5 y: 16.4% vs 18.2%; HR, 0.93 (95% CI, 0.80-1.08)|Invasive strategy led to modest improvement in angina-related health status|

(Continued)

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Table 4. Continued

|Trial (year)|Study population (sample size, n)|Randomized intervention|Age included, y|Specific results in older adults|Primary end point|Secondary end points| |---|---|---|---|---|---|---| |PREVENT (2024)|Stable coronary disease or ACS with non-flow-limiting (FFR >0.80) nonculprit vulnerable plaques by intracoronary imaging|PCI vs OMT alone|Mean ≈65; ≈1/3 of patients ≥75*|Results specifically for older adult cohort not published|Primary composite of MACE at 2 y: 0.4% (PCI) vs 3.4% (OMT); P=0.0003|Results consistent across components of the composite, no significant difference in serious clinical or adverse events|

Trials included in the table were required to have ≥2 of the following comparator groups: medical therapy, percutaneous coronary intervention (PCI), or coronary artery bypass grafting (CABG). BARI 2D indicates Bypass Angioplasty Revascularization Investigation 2 Diabetes; BEST, Bypass Surgery Versus Everolimus-Eluting Stent Implantation for Multivessel Coronary Artery Disease; CAD, coronary artery disease; CCSC, Canadian Cardiovascular Society Classification; COURAGE, Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation; EF, ejection fraction; EO-5D-5L, EuroOol 5-Dimensions 5-Levels Questionnaire; EXCEL, Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization; FFR, fractional flow reserve; FREEDOM, Future Revascularization Evaluation in Patients With Diabetes Mellitus: Optimal Management of Multivessel Disease; HF, heart failure; HFrEF; heart failure with reduced ejection fraction; HR, hazard ratio; ISCHEMIA, International Study of Comparative Health Effectiveness With Medical and Invasive Approaches; MACE, major adverse cardiovascular event; MACCE, major adverse cardiac or cerebrovascular event; MOBLE, PCI vs CABG in the Treatment of Unprotected Left Main Stenosis; OMT, optimal medical therapy; PRECOMBAT, Premier of Randomized Comparison of Bypass Surgery Versusi Angioplasty Using Sirolimus-Eluting Stent in Patients With Left Main Coronary Artery Disease; PTCA, percutaneous transluminal coronary angioplasty; OoL, quality of life; SAO, Seattle Angina Questionnaire; SF-36, Short Form-36 Health Survey; STICH, Surgical Treatment for ischemic Heart Failure; SYNTAX, Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery; and TIME, Trial of Invasive versus Medical Therapy in Elderly Patients.

*Sample size of ≥75-year-old cohort for FAME-2 (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation 2), ORBITA (Objective Randomised Blinded Investigation With Optimal Medical Therapy of Angioplasty in Stable Angita), ORBITA-2, and PREVENT (Preventive PCI or Medical Therapy Alone for Vulnerable Ath-erosclerotic Coronary Plaque) were provided by email communication with the study principal investigators.

were not seen in older patients (>63.3 years) compared with younger patients ($<63.3$ years: $P_{interaction} = 0.001$). However, the treatment effect appeared consistent for angina frequency improvement with CABG at 12 and 24 months in participants >75 years of age.$^{144}$ The NOBLE trial (PCI vs CABG in the Treatment of Unprotected Left Main Stenosis) enrolled 1201 patients with left main CAD ($<83%$ stable angina), randomizing patients to PCI versus CABG, and found a significantly higher rate of major adverse cardiac or cerebrovascular events at 5 years with PCI (28%) versus CABG (18%; hazard ratio, 1.51 [95% CI, 1.13–2.00]; P=0.004).$^{145}$ Results for participants ≥75 years of age were not specifically reported. NOBLE enrolled 622 patients ≥67 years of age (mean age, 73 years) and 77 patients >80 years of age. Among older participants, the rate of major adverse cardiac or cerebrovascular events was higher with PCI (35.7%) versus CABG (22.3%; P=0.0004), driven by higher rates of MI (10.8 versus 3.8%; P=0.0009) and repeat revascularization (19.5 versus 10.0%; P=0.002).$^{146}$ A meta-analysis of 3 CABG versus PCI trials (BEST [Bypass Surgery Versus Everolimus-Eluting Stent Implantation for Multivessel Coronary Artery Disease], PRECOMBAT [Premier of Randomized Comparison of Bypass Surgery Versus Angioplasty Using Sirolimus-Eluting Stent in Patients With Left Main Coronary Artery Disease], and SYN-TAX) included 1079 older adults (70–89 years of age; 550 CABG versus 529 PCI; ≈60% stable angina) and demonstrated that CABG was associated with lower risk of all-cause death, MI, stroke, or repeat revascularization in older participants.$^{147}$ There was also a consistent point estimate for benefit with CABG in the 131 participants

$\ge$80 years of age included in the meta-analysis. Available evidence suggests that CABG provides clinical benefit with acceptable safety in selected older adults with left main or multivessel CAD. Treatment decisions should be individualized, weighing surgical risk, anatomic complexity, patient preferences, and geriatric syndromes.

When Is Surgery Preferable?

Older patients with substantial CAD that warrants revascularization are often excluded from RCTs comparing PCI and CABG. However, older patients who undergo coronary revascularization receive benefits such as relief of symptoms, reduced risk of future MI, and improved survival rates. Similar to younger patients, older patients have been found to have improved survival, lower risk of repeat revascularization, lower risk of subsequent MI, and higher perioperative mortality rates after CABG compared with PCI in retrospective studies,$^{149}$ retrospective studies with propensity score modeling,$^{149}$ and meta-analyses.$^{150}$ Comparable outcomes between PCI and CABG were noted in a subgroup analysis and extended follow-up of a large RCT.$^{151}$

Older patients may have a higher burden of comorbidities and may have unique preferences regarding treatment compared with younger patients. Thus, a careful assessment is warranted when considering the options of PCI or CABG for coronary revascularization. This assessment includes the evaluation of technical candidacy and potential procedural risk of each option, a heart team discussion, and consideration of patient preferences, cognitive function, and life expectancy.

A heart team discussion regarding treatment of an older patient would include treatment options including

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guideline-directed medical therapy, PCI, and CABG. Coronary anatomy, comorbidities, procedural factors, and patient factors should be considered.$^{111}$ It is also recommended that patient preferences, cognitive function, and life expectancy be considered when determining revascularization strategy in older patients.$^{111}$ Shared decision-making including the patient and the patient's support system allows for consideration of the financial impact of treatment on the patient and the patient's family, the impact of alteration of QoL after treatment, the patient's personal goals and cultural beliefs, the patient's health literacy, and social determinants of health.$^{111}$ An older patient who is employed may decide on the least invasive option to facilitate return to work, or may prefer to prioritize QoL and a short hospitalization over longer-term benefits. Important patient factors to consider in revascularization treatment decisions include comorbidities, frailty, nutritional status, immunocompetence, functional and cognitive status, availability of social support, likelihood and safety of dual antiplatelet therapy (DAPT) adherence, need for other cardiac procedures, and estimated life expectancy.$^{1,3}$

Technical feasibility and procedural risk are also considered when evaluating revascularization treatment options in older patients. Important considerations for CABG include calculation of the Society of Thoracic Surgeons Predicted Risk of Mortality; the size and degree of calcification of the coronary arteries and likely potential for grafting; the available conduit for bypasses, including the left internal mammary artery; the degree of calcification of the ascending aorta (to permit cannulation, cross clamp, and placement of proximal anastomoses); and left ventricular ejection fraction. Calculation of the Society of Thoracic Surgeons Predicted Risk of Mortality is recommended when considering CABG$^{111}$; however, in a 75-year-old patient with 3-vessel CAD, the Society of Thoracic Surgeons Predicted Risk of Mortality is only increases by only 0.328% in an 80-year-old patient.$^{152}$ When considering the technical feasibility of PCI, assessment of possible access site complications, degree of coronary calcification, presence of trifurcation lesions (particularly with left main stenosis), tortuosity of target vessel, length of lesion to be treated, the potential success of crossing a coronary lesion, and the potential need for hemodynamic support is important.

After consideration of both coronary revascularization options, it may be evident that one option is more appropriate than another in the older patient (Figure 5). CABG is often more appropriate in patients with multivessel CAD, complex left main stenosis, diabetes, low left ventricular ejection fraction with suitable anatomy, contraindication to DAPT therapy, or severe in-stent restenosis. PCI is often more appropriate in patients with advanced age, reduced life expectancy, or severe left ventricular dysfunction combined with high surgical risk factors,

including frailty, poor functional or cognitive status, multiple comorbidities, severely calcified or porcelain aorta, poor bypass conduit, or lack of bypass conduit. In those high-risk older patients, PCI can achieve meaningful symptom relief with lower up-front morbidity risk. These are consistent with findings in patients with 3-vessel or left main disease who underwent PCI after they were determined to be ineligible for CABG after a heart team discussion. The most common reasons for CABG inelli-cetermined to be ineligible, severe systolic dysfunction, advanced age, severe cerebrovascular disease, severe lung disease, renal insufficiency, malignancy, severe peripheral artery disease, morbid obesity, or cachexia (Figure 6).$^{153}$

COMPLETE VERSUS CULPRIT-ONLY REVASCULARIZATION IN OLDER ADULTS

Several trials have investigated the question of culprit-only versus complete revascularization in patients with ACS, but most have excluded older patients (≥75 years of age). The COMPLETE trial (Complete vs Culprit-Only Revascularization to Treat Multivessel Disease After Early PCI for STEM) demonstrated that complete revascularization was superior to culprit-only revascularization at reducing death or MI in patients presenting with STEMI. The mean age of the 4041 participants enrolled in this trial was 62 years.$^{154}$ The FULL REVASC trial (FER-Guidance for Complete Non-Culprit Revascularization) evaluated physiology-guided complete revascularization compared with usual care among 1542 patients with STEMI and multivessel CAD who underwent culprit vessel PCI.$^{155}$ The mean age of participants enrolled in that trial was 65 years. There is sparse evidence regarding the benefits and risks of complete versus culprit-only revascularization in older adults (≥75 years) presenting with ACS. The FIRE trial (Functional Assessment in Elderly MI Patients With Multivessel Disease)—which enrolled 1445 participants age ≥75 years from 34 sites in Italy, Spain, or Poland who were admitted with STEMI or NSTEMI, underwent successful PCI of the culprit lesion, and had multivessel disease with ≥1 nonculprit lesion with a minimum vessel diameter of 2.5 mm and a visually estimated stenosis of 50% to 99%—attempted to bridge this evidence gap.$^{156}$ After successful culprit PCI, patients were randomized to receive either culprit-only treatment or physiology-guided complete revascularization. Patients in the physiology-guided complete revascularization group underwent PCI of all functionally significant nonculprit lesions. Patients in the culprit-only group did not receive additional physiologic assessment or nonculprit lesion revascularization. The primary outcome was a composite of death, MI, stroke, or ischemia-driven coronary revascularization occurring at 1 year. The primary outcome occurred in 113 patients (15.7%) in the complete revascularization group and 152 patients (21.0%) in the culprit-only group,

CLUNICAL STARTEMENTS AND GUIDELIMES

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 Figure 5. Choosing among coronary revascularization options.

Percutaneous coronary intervention (PCI) is often more appropriate in patients with advanced age or reduced life expectancy, severe left ventricular (LV) dysfunction, frailty, poor functional status, poor cognitive status, multiple comorbidities, severely calcified or porcelain aorta, poor bypass conduit, or lack of bypass conduit. Factors that are more appropriate for coronary artery bypass grafting (CABG) include multivessel coronary artery disease (MV CAD), complex left main (LM) stenosis, diabetes, low left ventricular ejection fraction (LVEF), contraindication to dual antiplatelet therapy (DAPT), or severe in-stent restenosis.

with a number needed to treat (benefit) of 19 patients. Secondary outcomes included a composite end point of cardiovascular death or MI at 1 year, which was also reduced with a physiology-guided complete revascularization strategy compared with a culprit-only strategy. All individual components of the primary outcome except for stroke were lower in the physiology-guided complete revascularization group. There was no difference between the 2 groups in terms of the incidence of a composite of contrast-associated acute kidney injury, stroke, or bleeding at 1 year. Data from this trial provided insights into the safety and efficacy of physiology-guided complete revascularization in older patients with ACS and multi-vessel disease. A meta-analysis of trials evaluating complete versus culprit-only revascularization that included older adults, including the FIRE results and the COM-PLETE subgroup analysis results of participants ≥75 years of age, found that complete revascularization was

associated with reduced MACEs without significant concomitant increases in acute renal injury or major bleeding.$^{157}$ COMPLETE-2—a prospective, multicenter RCT comparing a strategy of physiology-guided complete revascularization with angiography-guided complete revascularization in patients with STEMI or NSTEMI and multivessel CAD who have undergone successful culpritlesion PCI—is underway. COMPLETE-2 is planning to enroll all adults with no age cutoff; inclusion of older adults will supplement the current evidence provided by the FIRE trial on complete revascularization in older adults.

AORTIC STENOSIS AND CAD IN OLDER ADULT POPULATIONS

Aortic stenosis is a disease of the aging population that is frequently observed with concomitant CAD. The

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|Information-Sharing Considerations|Geriatric Considerations|Final Goal: Shared Decision Making|Improved Evidence|Other Considerations| |---|---|---|---|---| |Cognitive impairment use simple language; check for understanding Hearing/Visual Impairment provide assistive devices; use large fonts. Healthy literacy: tailor material; use visual aids.Cultural spiritual factors: align care with patient beliefsFamily/Caregiver involve family; offer resources|Multimorbidity Prioritize treatments with overall benefit.Frailty Consider less invasive options.Disability Adjust plans for physical limitations.Social Determinants Account for socio-economic factors.Patient Preferences Base decisions on patient goals.|Collaborative Process Use tools to help patients choose; involve them in decision-making.|Older Adults in Trials Include older adults in studies.Patient-Centered Outcomes Focus on quality of life.Chent Equity Ensure diverse population inclusion.|Patient-Centered Align treatments with patient goals: focus on independence, mobility, and quality of life.Care Coordination Smooth transitions with a multidisciplinary team.Shared Decision MakingEngage patients/families; use tools for values-based decisions.Serious Illness Conversations Discuss advance care plans and palliative options for holistic support.Cardiac Rehabilitation Promote center or home-based rehab; address barriers like cost and accessibility.|

Figure 6. Key considerations for careful assessment of revascularization options in the geriatric population requires tailored communication that addresses unique health needs, collaborative decision-making, inclusion in research, and holistic, patient-centered care.

Careful assessment of revascularization options in the geriatric population requires tailored communication that addresses unique health needs, collaborative decision-making, inclusion in research, and holistic, patient-centered care.

widespread adoption of TAVR has offered a less-invasive treatment option for patients diagnosed with severe aortic stenosis. This has been particularly beneficial for older adults, many of whom were previously deemed at high risk or inoperable for surgical aortic valve replacement.$^{158}$ Data from PARTNER I (Placement of Aortic Transcatheter Valve Trial), which only included the highest-risk patients, showed that there was significant mortality benefit associated with TAVR compared with medical management, even in this high-risk population.$^{159}$

There is often considerable overlap between symptoms of CAD and aortic stenosis, as well as a large proportion of patients (15%-80%) who are found to have both disease processes.$^{158}$ The 2020 American College of Cardiology/AHA guideline for the management of patients with valvular heart disease recommends an individualized approach to treatment of CAD before TAVR, and that patients with substantial left main or proximal CAD undergo revascularization before TAVR.$^{158}$ The NOTION-3 trial (Revascularization in Patients Understanding Trancatheter Aortic Valve Implantation) investigated the impact of performing PCI alongside TAVR in patients with both severe aortic stenosis and CAD. The study found that patients who underwent PCI had a significantly lower incidence of MACEs-defined as death, MI, or urgent revascularization—compared with those receiving only conservative treatment.$^{160}$ However, PCI was also associated with an increased risk of bleeding. These findings suggest that PCI may offer benefits for certain patients undergoing TAVR, but risks such as

bleeding complications must be considered.$^{160}$ For others, it is recommended and safe to proceed with valve replacement and then reassess symptoms to help guide management.$^{161}$ This is likely even more relevant among the older adult population of patients, where revascularization and postprocedure DAPT carry additional risk and management considerations.

For patients with an indication for coronary revascularization, the same procedural planning considerations and risks discussed for the older adult population apply to those undergoing TAVR, with potentially greater associated risks in the setting of severe aortic stenosis. The timing of intervention is an important consideration.$^{162}$ Revascularization before, simultaneous with, or after TAVR are potential options. The risks and benefits of staged versus combined procedures must be weighed. In appropriately selected older adults with concurrent aromatic stenosis and CAD, treatment strategies may include TAVR with staged or concomitant PCI or surgical aerobic valve replacement with CABG. The choice should be guided by anatomic complexity, frailty, surgical risk, and patient-centered goals of care. Chronic kidney disease is more common in the older adult population, and in this scenario, it may be prudent to stage the PCI and TAVR procedures rather than combining them. For patients with high-risk coronary anatomy or where there may be difficulty accessing the coronaries after TAVR valve implantation, revascularization before TAVR is likely beneficial. For an individual with critical aortic stenosis, the TAVR procedure likely takes priority. Beyond timing, there

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may be less concern regarding the need to reaccess the coronary arteries after TAVR in older compared with younger patients, which can influence the decision regarding type of TAVR valve. Overall, revascularization surrounding the timing of TAVR should be individualized in terms of whether to revascularize as well as timing of revascularization while weighing the unique patient-specific clinical and anatomic risks versus benefits of coronary revascularization.

APPROACH FOR OLDER ADULTS AND TECHNICAL CONSIDERATIONS

Advancements in health care delivery systems, critical care management, technical expertise, and device technology have allowed the application of PCI and other endovascular procedures to older and higher-risk patients. With respect to older patients with ACS and complex CAD requiring PCI, for example, advancements have resulted in significant improvements in survival and QoL. However, older patients are at elevated risk of procedural morbidity and mortality, and age and geriatric syndromes affect both short- and long-term outcomes of procedural interventions. The optimization of procedural outcomes in older adults requires comprehensive patient assessment; appropriate patient selection; awareness of age-specific physiologic, anatomic, and clinical challenges; and strict adherence to general and age-specific procedural best practices.

Fundamental to patient selection is understanding the relative benefits versus risks associated with a given procedure. Various online resources and mobile apps can assist in this endeavor, including the Society of Thoracic Surgeons/American College of Cardiology TAVR In-Hospital Mortality Risk tool, the TIMI and GRACE risk scores for assessment of in-hospital and 6-month mortality risk in STEMI, and the Society for Cardiovascular Angiography & Interventions PCI Risk tool for predicting peri-PCI morbidity and mortality. Beyond risk prevention models, clinical experience and implementation of heart team models, inclusive of geriatrics and palliative care medicine, are imperative in complex medical decision-making involving elderly patients and identification of when interventions should be considered futile.$^{1}$ Understanding and respecting patient values and preferences is necessary when weighing the potential tradeoffs of complex cardiovascular interventions and crucial to the shared decision-making process. Despite proven benefits of the shared decision-making process, its application in older adults can be complicated by cognitive and sensory impairments, caregiver dependence, involvement of multiple family members and their respective viewpoints and opinions, acuity of presentation, and limitations on clinician time and ability to effectively communicate the necessary information.$^{163,164}$

Various age-related factors can complicate procedural-related success and safety. The process of cardiovascular and renal aging contributes to endothelial dysfunction, increased systemic inflammation, increased arterial stiffness and calcification, decreased responsiveness to beta-adrenergic stimulation, impaired ventricular relaxation, and renal tubular dysfunction with altered sodium and potassium handling and urine-concentrating ability.$^{1}$ These changes can in turn greatly affect the older patient's ability to tolerate changes in hemodynamics incurred with sedation, blood loss, or acute cardiac conditions. Older patients are more likely to have systemic atherosclerosis as well as increased arterial calcification and tortuosity.$^{165-167}$ Aorto-subclavian and iliofemoral calcification and tortuosity, for example, are more prevalent in older patients and have been shown to adversely affect procedural success and safety in both transradial and femoral-access PCI procedures.$^{168,169}$ Successful navigation of these challenges often requires specific tools, skills, and experience.$^{170}$ Older patients are more likely to have preexisting conditions, such as lung disease, hypertension, heart failure, CAD, valvular heart disease, cognitive impairment, atrial fibrillation, and renal dysfunction, which can increase their susceptibility to procedural complications such as bleeding, acute kidney injury, stroke, and MI. These conditions demand increased attention to preprocedural planning and intraprocedural attention to hemodynamics and respiratory status, adherence to best practices in endovascular techniques and protocols, and knowledge of age-related sensitivities to medications and required dose adjustments.$^{251,171}$

PHARMACOTHERAPY IN PATIENTS UNDERGOING CORONARY REVASCULARIZATION

Age-related pharmacokinetic and pharmacodynamic changes are important considerations in selecting procedural pharmacotherapy in older patients undergoing revascularization. Reduced renal and hepatic function can lead to prolonged duration of administered mediations, changes in body composition can affect drug distribution, and altered receptor sensitivity can affect response to medications in older patients undergoing PCI (Table 5).$^{17}$

Conscious sedation is frequently administered during PCI, with the most commonly used regimen consisting of a benzodiazepine and an opiate antagonist.$^{172}$ Limited data exist evaluating the best approach to moderate sedation in older patients undergoing cardiac catheterization; therefore, society guidance considerations have been proposed.$^{173,174}$ For older patients, proposed considerations include to use an opioid-based regimen without benzodiazepines in an effort to avoid delirium while keeping in mind the potential delay in antiplatelet

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Table 5. Overview of Age-Related Pharmacokinetic and Pharmacodynamic Changes and Their Implications for Pharmacotherapy in Cardiovascular Procedures

|Pharmacokinetic process|Physiologic change|Pharmacokinetic effect|Medications affected|Suggested clinical actions| |---|---|---|---|---| |Distribution|↓ Total body water, ↓ lean muscle mass, relative ↑ in body fat|Larger volume of distribution of lipophilic medications and smaller volume of distribution of hydrophilic medications|Heparin, enoxaparin|Use weight-based dosing; monitor for exaggerated effects of lipophilic agents| |Metabolism|↓ Hepatic blood flow, possible ↓ in hepatic CYP450 activity|Longer duration of effect of hepatically metabolized medications|Midazolam, diazepam, opioid antagonists, diphenhydramine|Use lower initial doses; avoid long-acting benzodiazepines; monitor for sedation| |Excretion|↓ Glomerular filtration rate|Longer duration of effect of really cleared medications|Eptifibatide, tirofiban, enoxaparin, bivalirudin|Ensure renal dose adjustment; avoid agents with narrow therapeutic index in case of renal impairment| |Altered receptor sensitivity|↑ Sensitivity to centrally acting agents|↓ Dose requirement for pharmacologic effect|Benzodiazepines (eg, midazolam, diazepam, opioid antagonists (eg, fentanyl, morphine), antihistamines (eg, diphenhydramine)|Prefer nonsedating options when possible; minimize dose; avoid combining CNS depressants|

CNS indicates central nervous system.

onset in oral P2Y12-naive patients.$^{173}$ Additional considerations include using lower initial doses of sedating and pain medication to balance comfort and safety.$^{174}$

DAPT with aspirin plus an oral P2Y12 inhibitor is the mainstay of therapy to prevent thrombotic events in older patients undergoing PCI. When selecting an oral P2Y12, consideration should be given to the agent selected, clinical presentation, timing of angiography, concomitant medications, and the risk for thrombotic and adverse events. For patients with SIHD undergoing PCI, guidelines provide a Class 1 recommendation for clopidogrel in addition to aspirin to reduce ischemic events, regardless of age. In addition, in the absence of known coronary anatomy, the guidelines state that evidence does not support routine pretreatment before angiography.$^{11}$

For older people presenting with ACS who undergo PCI, some variability has been observed with trial results of oral P2Y12 therapy over time. A substudy of the PLATO trial (A Comparison of Ticagrelor [AZD6140] and Clopidogrel in Patients With Acute Coronary Syndrome) that assessed outcomes of ticagrelor versus clopidogrel in patients ≥75 years of age compared with those <75 years of age reported that the clinical benefit and overall safety of ticagrelor versus clopidogrel was not significantly different in older versus younger patients. Approximately 73% of patients ≥75 years of age underwent PCI during the conduct of the trial.$^{175}$ More recently, the POP-ular AGE trial (Ticagrelor or Prasugrel Versus Clopidogrel in Elderly Patients With an Acute Coronary Syndrome and a High Bleeding Risk: Optimization of Antiplatelet Treatment in High-Risk Elderly) randomized patients ≥70 years of age with NSTE-ACS to clopidogrel versus ticagrelor or prasugrel, and results showed significantly fewer bleeding events in the clopidogrel group without an increase in the composite ischemic end point. In this trial, ≈50% of patients underwent PCI, and no interaction

was observed.$^{176}$ Guidelines suggest cautious use of pragugrel in patients ≥75 years of age$^{111}$ on the basis of the results of the TRITON trial (A Comparison of Prasugrel [CS-747] and Clopidogrel in Acute Coronary Syndrome Subjects Who Are to Undergo Percutaneous Coronary Intervention), which used a 10-mg maintenance dose of prasugrel and showed no net clinical benefit of prasugrel versus clopidogrel in patients ≥75 years of age due to higher rates of bleeding.$^{177}$ Recent trials have assessed a 5-mg maintenance dose of prasugrel in older people undergoing PCI. The Elderly ACS 2 trial randomized patients with ACS >74 years of age and undergoing PCI to clopidogrel or a reduced dose of prasugrel (5 mg daily). The trial was stopped early due to futility, but no significant differences in the primary composite ischemic end point were observed, whereas the reported rate of major bleeding was numerically higher in the prasugrel group.$^{178}$ In patients with atrial fibrillation undergoing PCI, minimizing bleeding risk while preserving anti-ischemic effects is crucial. Dual therapy with a direct oral anticogulant plus clopidogrel is generally preferred over triple therapy, particularly in older adults, based on data from trials such as PIONEER AF-PCI (A Study Exploring Two Strategies of Rivaroxaban [JNJ39039039; BAY-59-7939] and One of Oral Vitamin K Antagonist in Patients With Atrial Fibrillation Who Undergo Percutaneous Coronary Intervention) and AUGUSTUS (A Study of Apixaban in Patients With Atrial Fibrillation, Not Caused by a Heart Valve Problem, Who Are at Risk for Thrombosis [Blood Clots] Due to Having Had a Recent Coronary Event, Such as a Heart Attack or a Procedure to Open the Vesels of the Heart).$^{179,180}$ These regimens reduce bleeding events without a significant increase in thrombotic complications.

Guidelines do not recommend the routine use of intravenous platelet inhibitors during PCI.$^{111}$ Glycoprotein IIb/ Illa antagonists receive a 2a recommendation for use in

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patients with ACS undergoing PCI with a large thrombus burden or no or slow reflow; cangrelor receives a 2b recommendation as a reasonable strategy to reduce periprocedural ischemia during PCI in oral P2Y12-naive patients.$^{111}$ A subanalysis of CHAMPION PHOENIX (A Clinical Trial Comparing Cangrelor to Clopidogrel Standard Therapy in Subjects Who Require Percutaneous Coronary Intervention) reported no increase in major bleeding and similar efficacy of cangrelor compared with clopidogrel in patients ≥75 years of age compared with those <75 years of age.$^{181}$

Given the concern about bleeding risk with longer-term DAPT in older patients who have undergone PCI, recent strategies such as shortening the course of DAPT and antiplatelet deescalation (either early discontinuation of aspirin or changing from ticagrelor or prasugrel to clopidogrel after 1 to 3 months with or without the guidance of genotyping of platelet function testing) have been studied in an attempt to balance bleeding and ischemic risk.$^{182}$ A recently published systematic review of different durations of DAPT in older adults after PCI reported that abbreviated DAPT durations were associated with lower rates of bleeding with no observed increase in MACE rates.$^{183}$ Studies of deescalation strategies have shown reduced bleeding with no apparent increase in ischemic events, but most of the research has been conducted in patients of East Asian descent.$^{182}$

Unfractionated heparin (UFH) is the anticoagulant used most often during PCI in the United States. Guidelines provide a Class 1 recommendation for UFH during PCI to reduce ischemic events.$^{11}$ A Class 2b recommendation is made for bivalirudin as a reasonable alternative to UFH to reduce bleeding; intravenous enoxaparin at the time of PCI receives a 2b recommendation in patients with NSTE-ACS started on subcutaneous enoxaparin before PCI.$^{111}$ A subanalysis of patients ≥75 years of age enrolled in the VALIDATE-SWEEDEHEART trial (Bivalirudin versus Heparin in ST-Segment and Non-ST-Segment Elevation Myocardial Infarction in Patients on Modern Antiplatelet Therapy in the Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies Registry Trial) reported no differences in ischemic or bleeding outcomes between the UFH and bivalirudin groups, suggesting that bivalirudin may be a safe alternative to UFH in older patients undergoing PCI.$^{184}$

As discussed, age-related changes that can affect the pharmacokinetics and pharmacodynamics of medications as well as the potential for drug-drug interactions due to polypharmacy are important considerations when prescribing medications in older patients undergoing CABG. In general, a heart team discussion should be considered when making perioperative medication choices for older patients undergoing CABG. Recent guidelines provide limited guidance on age-specific recommendations for

medications in older patients undergoing CABG.$^{1}$ However, given the observation of geriatric syndromes being associated with an increased risk for adverse procedural outcomes, it is important to review several of the recommendations. In patients undergoing CABG, the guidelines provide a Class 1 recommendation for the use of an intraoperative insulin infusion to maintain a serum glucose level <180 mg/dL to reduce the risk of a sternal would infection and a Class 1 recommendation for the continuation of aspirin until the time of surgery in patients already taking aspirin preoperatively.$^{111}$ Because older people are at higher risk of CABG-associated bleeding complications, relevant recommendations include a Class 2a recommendation for patients undergoing CABG on an oral P2Y12 inhibitor to discontinue ticagrelor for 3 days, clopidogrel for 5 days, and prasugrel for 7 days before CABG to reduce the risk of major bleeding.$^{111}$ A Class 3 recommendation is made for initiating aspirin in the immediate preoperative period in patients who were previously not on aspirin undergoing elective CABG. A recent systematic review reported age as being an independent risk factor for delirium after CABG.$^{185}$ Given this, consideration should be given to anesthesia strategies and postoperative pain regimens that can reduce delirium risk.

NONINTERVENTIONAL CONSIDERATIONS

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When considering treatment options for older adults presenting for potential revascularization, multidisciplinary team-based care, patient education, and shared decision-making are particularly important for a strategy that is patient-centered.$^{186}$ Patient-centered care in geometric cardiology integrates clinical expertise and the latest evidence with the patient's health priorities, life goals, preferences, values, and beliefs.$^{187,188}$ Assessing what matters most to patients is foundational in shared decision-making.$^{51,189}$ Older adults are more likely than younger adults to prioritize the ability to remain independent, with a focus on maintaining mobility, functional status, and QoL rather than longevity.$^{28}$ CR, a Class 1 recommendation for secondary prevention of adults undergoing coronary revascularization,$^{103}$ provides an opportunity to deliver personalized approaches to cardiovascular and psychologic health in the context of their holistic health care needs.

Care Coordination

Continuity in care as older adults undergoing coronary revascularization transition from hospital to home or a rehabilitation facility is important given the greater prevalence of frailty, multimorbidity, depression, cognitive decline, diminished functional status, and higher symptom burden.$^{28}$ Decisions may need to be made for appropriate levels of care (eg, intensive care, long-term care facility,

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hospice), advanced care (eg, surgical intervention), and multidisciplinary care coordination (eg, primary care physicians, advanced practitioners, palliative care, other specialists).$^{187}$ To achieve optimum coordination of care, and in turn, optimal outcomes, a multidisciplinary team of physicians, geriatricians, nurses, exercise physiologists, dieticians, social workers, and the patient's support network is essential.$^{1}$ Geriatric comanagement is a model of care for older adults with medical complexity whereby a designated geriatrician or geriatrics-trained nurse provides concurrent care alongside the cardiovascular clinician.$^{190}$

Shared Decision-Making

Shared decision-making is a communication process by which patients and clinicians collaborate to choose treatments and care plans that most align with a patient's preferences, beliefs, values, and health goals.$^{191}$ Shared decision-making considering the patient's preferences and goals of care is vital to personalized, holistic care of older adults. In shared decision-making, clinicians provide evidence-based information about reasonable options and the patient provides expertise on their personal situation, values, preferences, and attitude toward risk (Figure 6).$^{164}$ Because older adults—particularly older patients from underrepresented racial or ethnic groups and older women—have been underrepresented in cardiovascular clinical trials or excluded on the basis of age or comorbidities, the evidence base from clinical trials to facilitate shared decision-making is particularly sparse in terms of patient-centered outcomes such as symptoms, function, or QoL.$^{192}$

Whereas older adults are a heterogeneous group, sharing medical information with older adults involves potential challenges, including cognitive impairment, hearing or visual impairment, and low health literacy.$^{164}$ Contextual complexity, including multimorbidity, frailty, cognitive impairment, and social determinants of health, also presents challenges in shared decision-making. Situational complexity and social determinants of health may also influence disease burden, access to care, the choice of revascularization strategy, and health outcomes.$^{192}$ Shared decision-making with older adults and their support network is enhanced with input from relevant multidisciplinary colleagues.$^{164}$ In treatment decisions that have no single best choice, patient decision aids may be useful for older adults. The most recent Cochrane review of decision aids (209 studies involving 107 698 participants) found that decision aids resulted in improved knowledge, accurate risk perceptions, and an active role in decision-making.$^{193}$

Advance Care Planning

Helping patients and their families understand the risks and benefits of treatments for advanced CVD through

advance care planning and advance directives is a common and important form of shared decision-making.$^{191}$ The intent of palliative care is to improve QoL and reduce suffering among patients with serious illness. A 2016 AHA policy statement recognizes the benefits of advance care planning and shared decision-making in advanced CVD and suggests that “care planning and decision-making processes, including discussions concerning goals of care, postdischarge needs, options, and resources, are patient-directed and patient-centered and are conducted in consultation with the patient's surrogate decision-makers, family caregivers, and professionals responsible for the patient's care, including palliative care generalists and specialists as needed.”$^{194}$

Patient Education

The lack of synthesis of educational interventions for secondary prevention or structure of education delivery for older patients with CVD provides little guidance for practice. However, a meta-analysis of 73 studies (n=24985; mean age, 60.5±5.7 years) found that patient education for secondary prevention, in various delivery modes and intensities, improved multiple self-reported health behaviors in patients with CAD.$^{195}$ Patient education also reduced anxiety and depressive symptoms in patients with coronary heart disease.$^{196}$ Nurses are the most frequent providers of educational interventions, particularly at hospital discharge and outpatient care, to ensure follow-up at home. In many nurse-led CR programs, nurses work collaboratively with other health care professionals to deliver patient education on the management of CVD risk factors, nutrition counseling, psychosocial interventions, and tobacco cessation interventions.$^{197}$

Cardiac Rehabilitation

CR is a multidisciplinary, systematic yet personalized program to help patients achieve cardiovascular health and guideline-directed targets for control of risk factors.$^{198}$ The AHA/American College of Cardiology provides a Class 1 recommendation for center-based CR for patients undergoing coronary revascularization.$^{103}$ Evidence substantiates the role of center-based CR (CBCR) exercise participation for improving CVD risk factors and reducing recurrent CVD adverse events and mortality risk in older adults.$^{199}$ Systematic reviews and meta-analyses of RCTs of CR have consistently demonstrated these outcome benefits in patients with ACS after coronary revascularization and heart failure with reduced ejection fraction,$^{200}$ although the mean age of trial participants was 56 years (range, 44–77).

CR provides an opportunity to develop personalized approaches to cardiovascular health in the context of older adults' aggregate health care challenges.$^{201,202}$ In addition, CBCR fosters socialization among older adults

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who otherwise may have limited social options.$^{199}$ Furthermore, CR provides a unique opportunity for both medication reconciliation and direct observation of tolerance of medications during supervised exercise, allowing for a patient-centered approach to optimize medical therapy while reducing risks of adverse events, particularly falls, in older adults.$^{202}$

Despite the benefits of CR, participation declines with increasing patient age, and only 25% of older patients eligible for CR participate or complete the program.$^{203}$ Women also tend to participate less often than men across all ages, but because women tend to outlive men, these gaps worsen among older adults.$^{204}$ Common barriers to CBCR among older adults include a lack of understanding among patients and clinicians of the value of CBCR, prohibitive logistics given that many older adults cannot drive, unaffordable copayments for CBCR for patients on fixed incomes, and inflexibility in format to achieve personalized therapeutic approaches in CBCR that are tailored to the wide range of needs and circumstances among older adults.$^{201}$

To address barriers to attendance and extend the reach of secondary prevention services, home-based CR or hybrid CR models of care have been developed. A scientific statement summarizing evidence on home-based CR with either synchronous or asynchronous communication reported short-term benefits that were similar to those with CBCR.$^{205}$ Home-based CR consists of the core components of CBCR programs but is delivered through regular contact with health care professionals through telephone calls or mobile technology. Home-based CR is reasonable to consider for low- to moderate-risk patients who otherwise cannot attend traditional CBCR, although efficacy for adults with frailty or cognitive impairment, or who are prone to falls, is unclear.$^{205}$

GAPS IN KNOWLEDGE AND FUTURE DIRECTIONS

Gaps in knowledge regarding coronary revascularization in older adults persist due to limited representation in clinical trials. Evidence is needed to guide revascularization strategies, timing, and approach in the context of frailty, multimorbidity, and other geriatric syndromes. Future research should focus on RCTs that include a broader spectrum of older adults (≥75 years of age). Comprehensive assessments of frailty, cognitive function, and life expectancy should be integrated into revascularization guidelines. Developing tools for individualized decision-making that incorporate patient preferences, geriatric risks, and holistic care outcomes is essential for optimizing management. Proteomic and genomic profiling could enhance patient stratification by identifying biomarkers

associated with aging, frailty, and cardiovascular risk. Moreover, there is a need for better pharmacologic approaches tailored to older adults, considering age-related changes in drug metabolism and increased polypharmacy risks. Enhanced shared decision-making frameworks that incorporate patient preferences, life expectancy, and personalized risk profiles are essential to guide optimal revascularization strategies for older adults.

CONCLUSION

The aging of the world population and the growing burden of DVD present unique challenges that demand specialized care for older adults undergoing revascularization. These patients with age-related physiologic changes, complex coronary anatomy, and prevalent genetic syndromes require a nuanced and individualized approach to management. Coronary revascularization can offer benefits, such as symptom relief and improved outcomes, but the risks associated with invasive procedures necessitate careful consideration of clinical status, frailty, and personal goals. Future research should aim to close knowledge gaps by including diverse older adults in clinical trials, using proteomic and genomic profiling for better risk stratification, and advancing decision-making frameworks that emphasize personalized care.

ARTICLE INFORMATION

The American Heart Association makes every effort to avoid any actual or potential conflicts of interest that may arise as a result of an outside relationship or a personal, professional, or business interest of a member of the writing panel. Specifically, all members of the writing group are required to complete and submit a Disclosure Questionnaire showing all such relationships that might be perceived as real or potential conflicts of interest.

This statement was approved by the American Heart Association Science Advisory and Coordinating Committee on July 29, 2025, and the American Heart Association Executive Committee September 30, 2025. A copy of the document is available at https://professional.heart.org/statements by using either "Search for Guidelines & Statements" or the "Browse by Topic" area. To purchase additional reprints, call 215-356-2721 or email Meredith.Edelman@wolterskuwer.com

The American Heart Association requests that this document be cited as follows: Damluji AA, Nanna MG, Mason P, Lowenstern A, Orkaby AR, Washam JB, Kolkailah AA, Beckie TM, Dangas G, Lawton JS; on behalf of the American Heart Association Interventional Cardiovascular Care Committee of the Council on Clinical Cardiology; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular and Stroke Nursing; Council on Cardiovascular Surgery and Anesthesia; and Council on Quality of Care and Outcomes Research. Circulation. 2025;152:e—e—e... doi: 10.1161/CIR.00000000000001387

The expert peer review of AHA-commissioned documents (eg, scientific statements, clinical practice guidelines, systematic reviews) is conducted by the AHA Office of Science Operations. For more on AHA statements and guidelines development, visit https://professional.heart.org/statements. Select the "Guidelines & Statements" drop-down menu, then click "Publication Development"

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

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Disclosures

Writing Group Disclosures

|Writing group member|Employment|Research grant|Other research support|Speakers' bureau/ honoraria|Expert witness|Ownership interest|Consultant/ advisory board|Other| |---|---|---|---|---|---|---|---|---| |Abdulla A. Damluji|Cleveland Clinic Foundation|None|None|None|None|None|None|None| |Michael G. Nanna|Yale School of Medicine, Yale New Haven Hospital|None|Associated Research Funding: Shockwave Medical, Inc†|None|None|None|None|None| |Theresa M. Beckie|University of South Florida College of Nursing/College of Medicine|None|None|None|None|None|None|None| |George Dangas|Icahn School of Medicine at Mount Sinai Cardiovascular Institute|None|None|None|None|None|None|None| |Ahmed A. Kolkailah|University of Texas Southwestern Medical Center|None|None|None|None|None|None|None| |Jennifer S. Lawton|Johns Hopkins|None|None|None|None|None|None|None| |Angela Lowenstern|Vanderbilt University|None|None|Medtronic*|None|None|None|None| |Peter Mason|University of North Carolina-Chapel Hill School of Medicine|None|None|None|None|None|None|None| |Ariela R. Orkaby|VA Boston Healthcare System Geriatric Research Education and Clinical Center|None|None|None|None|None|None|None| |Jeffrey B. Washam|Duke University Hospital Heart Center DUMC|Chiesi USA (research support)*|None|None|None|None|Faraday Pharmaceuticals*|American|

This table represents the relationships of writing group members that may be perceived as actual or reasonably perceived conflicts of interest as reported on the Disclosure Questionnaire, which all members of the writing group are required to complete and submit. A relationship is considered to be "significant" if (a) the person receives ≥$5000 during any 12-month period, or ≥5% of the person's gross income; or (b) the person owns ≥5% of the voting stock or share of the entity, or owns ≥$5000 of the fair market value of the entity. A relationship is considered to be "modest" if it is less than "significant" under the preceding definition.

*Modest.

†Significant.

Reviewer Disclosures

|Reviewer|Employment|Research grant|Other research support|Speakers' bureau/ honoraria|Expert witness|Ownership interest|Consultant/ advisory board|Other| |---|---|---|---|---|---|---|---|---| |Ian C. Gilchrist|Northwell Health|None|None|None|None|None|None|None| |Ajar Kochar|Brigham and Women's Hospital, Harvard Medical School|None|None|None|None|None|None|None| |Min Ji Kwak|McGovern Medical School, University of Texas Health Science Center at Houston|None|None|None|None|None|Novo Nordisk†|None| |Jon R. Resar|Johns Hopkins University School of Medicine|Medtronic (Pl for multiple TAVR studies)†|None|None|None|None|None|None| |Jennifer Anne Rymer|Duke University Medical Center|None|None|None|None|None|None|None|

This table represents the relationships of writing group members that may be perceived as actual or reasonably perceived conflicts of interest as reported on the Disclosure Questionnaire, which all members of the writing group are required to complete and submit. A relationship is considered to be "significant" if (a) the person receives ≥$5000 during any 12-month period, or ≥5% of the person's gross income; or (b) the person owns ≥5% of the voting stock or share of the entity, or owns ≥$5000 of the fair market value of the entity. A relationship is considered to be "modest" if it is less than "significant" under the preceding definition.

*Modest.

†Significant.

CLINAL STATE STAREMENTS GILINAL STARESTRE

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Coronary Artery Revascularization in Older Adults

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