Management of Acute Coronary Syndrome in the Older Adult Population: A Scientific Statement From the American Heart Association
Abstract
Diagnostic and therapeutic advances during the past decades have substantially improved health outcomes for patients with acute coronary syndrome. Both age-related physiological changes and accumulated cardiovascular risk factors increase the susceptibility to acute coronary syndrome over a lifetime. Compared with younger patients, outcomes for acute coronary syndrome in the large and growing demographic of older adults are relatively worse. Increased atherosclerotic plaque burden and complexity of anatomic disease, compounded by age-related cardiovascular and noncardiovascular comorbid conditions, contribute to the worse prognosis observed in older individuals. Geriatric syndromes, including frailty, multimorbidity, impaired cognitive and physical function, polypharmacy, and other complexities of care, can undermine the therapeutic efficacy of guidelines-based treatments and the resiliency of older adults to survive and recover, as well. In this American Heart Association scientific statement, we (1) review age-related physiological changes that predispose to acute coronary syndrome and management complexity; (2) describe the influence of commonly encountered geriatric syndromes on cardiovascular disease outcomes; and (3) recommend age-appropriate and guideline-concordant revascularization and acute coronary syndrome management strategies, including transitions of care, the use of cardiac rehabilitation, palliative care services, and holistic approaches. The primacy of individualized risk assessment and patient-centered care decision-making is highlighted throughout.
Approximately 720 000 Americans experience an acute myocardial infarction (MI) or coronary artery disease (CAD)–related death per year, and >335 000 Americans have recurrent events annually.1 The older adult population is disproportionately affected. Adults ≥75 years of age constitute ≈30% to 40% of all hospitalized patients with acute coronary syndrome (ACS), and the majority of ACS-related death is observed in this segment of the population.2–4 These patients often present with heavy atherosclerotic plaque burden, anatomic complexities, calcifications, vessel tortuosity, ostial lesions, multivessel disease, and left main stenosis. In addition to such disease-specific therapeutic challenges, older adults are also more likely to present with concomitant geriatric syndromes that compound aggregate prognostic risk.5 Frailty, multimorbidity, cognitive impairment, functional decline, nutritional deficiencies, and polypharmacy are among a long list of geriatric domains that are endemic in the large and growing older population.6 Consideration of these geriatric complexities is crucial for optimal management of ACS amid contemporary health care trends.5
Clinical trials that are considered standards regarding the efficacy and safety of ACS therapeutics predominantly enrolled patients <75 years of age, and most did not include candidates with geriatric complexities. However, in contemporary clinical practice, cardiovascular, and geriatric risks, as well, are entwined, and both are relevant in regard to determining therapeutics that minimize adverse outcomes and achieve health states that are most likely to be valued by older patients.7 Timely differentiation between the different types of MI, especially MI with nonobstructive coronary arteries, is essential with related goals to avoid superfluous diagnostic tests, heterogeneity in clinical decisions, and underuse of treatments that are vital. These gaps highlight the need for updated recommendations for ACS management in older adults, with a synthesis of the information that has proliferated since the publication of the first American Heart Association (AHA) scientific statements on ACS in older adults.8,9 The 2007 AHA statement established the need for clinical studies enrolling older adult populations.10 This document is primarily concerned with adults ≥75 years of age because most of the gaps in knowledge exist in this age group.11
In this AHA scientific statement, we review age-related physiological changes in the heart and vascular systems that predispose to cardiovascular disease (CVD) and management complexities. We review commonly encountered geriatric syndromes and their influence on CVD outcomes. Guidelines-based revascularization and adjunctive strategies are emphasized, with relevant considerations regarding transitions of care, cardiac rehabilitation (CR), palliative care services, futility, and a holistic approach to care. Broader considerations regarding risk assessment and decision-making are highlighted.
Cardiovascular Aging
Cardiovascular Physiology
Normal aging is associated with multiple changes in cardiovascular structure and function that predispose older adults to CAD, myocardial ischemia, and ACS (Table 1).12 A hallmark of aging is increased stiffness of the aorta and large central arteries primarily attributable to increased collagen deposition and cross-linking in conjunction with degradation of elastin fibers. These changes lead to increased impedance to the left ventricular (LV) ejection and a widening of central aortic pulse pressure reflected in an age-related increase in systolic blood pressure and a decline in diastolic blood pressure, especially after 75 years of age.13 To compensate for increased aortic impedance and central systolic blood pressure, aging myocytes tend to hypertrophy, provoking both increased apoptosis and LV hypertrophy, as well. In turn, the increased impedance to ejection and higher systolic blood pressure give rise to increased myocardial work and myocardial oxygen demand, whereas the lower diastolic pressure is associated with decreased coronary perfusion pressure. Thus, aging increases susceptibility to an imbalance between myocardial oxygen demand and supply.
| Age-related change |
|---|
| Increased central aortic stiffness attributable to increased collagen cross-linking and elastin fiber degeneration |
| Altered left ventricular diastolic relaxation and increased myocardial stiffness |
| Decreased responsiveness to β-adrenergic stimulation |
| Impaired endothelium-mediated vasodilation |
| Altered balance between intrinsic thrombosis and fibrinolysis |
| Chronic low-grade inflammation (inflammaging*) |
| Implications for acute coronary syndrome |
| Increased impedance to left ventricular ejection, increased systolic blood pressure and pulse pressure, increased myocardial work and O2 demand, decreased coronary perfusion pressure |
| Increased resistance to coronary perfusion; predisposition to atrial fibrillation and heart failure with preserved ejection fraction |
| Decreased maximum heart rate and contractility, decreased peak cardiac output, decreased peripheral vasodilation |
| Decreased peak coronary blood flow and coronary flow reserve; increased atherogenesis; increase in vascular impedance as a result of impaired endothelium-mediated vasodilatation. |
| Increased risk for venous and arterial thromboembolism |
| Increased atherogenesis and geriatric syndromes, including frailty |
*
Not a normal age-related change but prevalent at advanced age.
Aging is also associated with increased collagen deposition in the myocardial interstitium and the deposition of lipofuscin and other moieties, as well. These factors and others lead to an increase in myocardial stiffness and impedance to LV filling with alteration in the diastolic filling pattern and increased force of left atrial contraction to maintain LV end-diastolic volume.12 Slowing of LV relaxation also contributes to age-related diastolic dysfunction. The net effect is an increase in LV diastolic pressure that further lowers coronary perfusion pressure, which is defined as the difference between aortic diastolic pressure and LV diastolic pressure.
Aging is also associated with impaired coronary endothelial function mediated primarily by a decline in nitric oxide synthase activity.14 As a result, aged coronary arteries have less capacity to upregulate coronary blood flow in response to increased myocardial oxygen demands, which predisposes older adults to type 2 MI and non–ST-segment–elevation MI (NSTEMI). In addition, endothelial dysfunction, along with inflammation, is a fundamental driver of atherosclerosis, thereby contributing to the increasing prevalence of both subclinical and overt CAD with advancing age. Furthermore, although chronic inflammation is not inherent to normal aging, it is a common accompaniment to many age-associated diseases and conditions, including diabetes, arthritis, and frailty.15 The combination of endothelial dysfunction and chronic inflammation provides a fertile milieu for the development and progression of CAD in older adults.
Additional age-related cardiovascular changes include diminished responsiveness to β-adrenergic stimulation and a nearly linear decline in maximum attainable heart rate (ie, maximum heart rate=220 – age), both of which contribute to an age-associated decline in peak cardiac output in response to physiological or pathological stress.16 Although this decline in cardiovascular reserve with increasing age does not directly lead to ischemia under normal circumstances, it increases the risk for the development of acute and chronic heart failure in older patients with CAD.17 Apart from the effects on the cardiovascular system, aging is associated with a shift in the intrinsic balance between thrombosis and fibrinolysis in favor of thrombosis.18 As a result, older adults are more likely to develop venous thromboembolic disease and arterial clots, including coronary thrombosis, the hallmark of type 1 MI, and left atrial appendage thrombus, as well, in patients with atrial fibrillation.17
Renal Aging
Although the physiology of aging has a broad effect on the cardiovascular system, kidney function is particularly pertinent to ACS, because it exacerbates morbidity and death, and also diminishes accuracy of diagnosis and difficulty of therapeutic decision-making. Aging kidneys undergo macro- and microanatomical changes such as kidney cysts, focal inflammation, decreased cortical volume, nephrosclerosis (age-related histological changes), and renal artery atherosclerosis. Other pathophysiological changes in the kidney include loss of glomeruli and tubules and increased interstitial fibrosis, which need to be differentiated from other disease syndromes, such as those associated with diabetes and hypertension. The aging kidney is also characterized by tubular dysfunction, decreased sodium reabsorption, potassium excretion, and urine-concentrating ability, leading to volume depletion and risk of drug toxicity, all of which may predispose to acute kidney injury (AKI). Chronic kidney disease (CKD) is also more likely to develop in older patients because of the longitudinal loss of kidney function associated with aging.19 CKD is associated with increased coronary calcium that has significant implications on revascularization strategies and outcomes.
Kidney disease evaluation includes assessment of kidney function by estimated glomerular filtration rate. The National Kidney Foundation and the American Society of Nephrology have recently recommended race-neutral equations or use of the CKD Epidemiology Collaboration equation with cystatin C.20 Additional indices for kidney function include urine test for albuminuria, serum electrolytes to evaluate for disorders of sodium, potassium, calcium, and phosphate, and for volume assessment, as well. Serum creatinine in older adults is less reliable than in younger adults because it may be spuriously low in the context of low muscle mass.
Implication of Kidney Disease on ACS
Cardiorenal syndrome is defined as a bidirectional pathophysiological disorder of both the heart and kidneys, which was initially classified into 5 different categories by Ronco.21 These 5 subtypes of cardiorenal syndrome are categorized on the basis of acuity and sequential organ involvement, which is discussed in detail in a previous AHA scientific statement and summarized in Supplemental Table 1.22 Cardiorenal syndrome type 1 is defined as an acute cardiac disease leading to AKI, typically caused by ACS, acute heart failure, or cardiac surgery. On the basis a systemic review and meta-analysis, Vandenberghe et al23 found that the prevalence of AKI in patients with ACS is 12.7%. A greater severity of AKI was associated with worse outcomes, including death (risk ratio‚ 3.53; 95% adjusted hazard ratio, 2.04–6.10), length of stay in the intensive care unit (ICU), and rehospitalizations. AKI in older patients typically presents with multiple comorbidities, including diabetes, hypertension, heart failure, and peripheral artery disease.
Considerations for Clinical Practice
1.
The cardiovascular aging process is characterized by increased stiffness of the aorta and large central arteries, concentric LV hypertrophy, elevated LV end-diastolic pressure, collagen deposition in the myocardial interstitium and impaired myocardial relaxation, impairment in the endothelial function of coronary arteries, diminished responsiveness to β-adrenergic stimulation, and an imbalance between thrombosis and fibrinolysis.
2.
The aging kidney is characterized by tubular dysfunction, decreased sodium reabsorption, potassium excretion, and urine-concentrating ability, predisposing to volume depletion and risk of drug toxicity, all of which increased risk for contrast-induced AKI in the context of ACS.
3.
Understanding of these pathophysiological changes is critical when evaluating guideline-directed medical therapy for ACS and for managing age-related risks to prevent physical, cognitive, or functional decline in older individuals.
Geriatric Syndromes
Geriatric syndromes are multifactorial conditions that are increasingly prevalent at older age. Whereas they are clinical syndromes, most stem from the same age-related physiological vulnerabilities that underlie CVD.15 Examples include multimorbidity, frailty, functional decline (cognitive and physical), delirium, sensory decline (hearing, vision, and pain), falls, and polypharmacy.17 It is notable that the incidence and prevalence of geriatric syndromes largely parallel the cardiovascular risk profile, such that older adults with low cardiovascular risk profiles are also at lower risk for the development of geriatric syndromes (Table 2).24 Conversely, older adults presenting with ACS are more likely to have a spectrum of diminished functional (physical and cognitive) reserves ranging from mild impairment to more significant decline. In addition, the presence of one or more geriatric syndromes may substantially affect clinical presentation, clinical course and prognosis, therapeutic decision-making, and response to treatment for ACS. It is therefore fundamental that clinicians caring for older patients with ACS be alert to the presence of geriatric syndromes and be able to integrate them into the care plan when appropriate (Figure 1).
| Geriatric syndrome | Diagnosis/prevalence | Prognosis | Disease management |
|---|---|---|---|
| Multimorbidity | ≥2 chronic conditions (cardiac and noncardiac) that are active simultaneously. Prevalence: 63% of adults 65–74 y old, 77% of adults 75–84 y old, and 83% of adults ≥85 y old. | ↑Short- and long-term prognostic risks attributable to CVD, and uncontrolled CVD and non-CVD risk factors, as well. | Confounds customary CVD symptoms and signs. Multiple diseases and clinicians often result in desynchronized or even contradictory aspects of care. ↑Likelihood that patients will experience high therapeutic burden. |
| Frailty | State of vulnerability relating to diminished physiological reserves across multiple physiological systems. Definition controversial: some define frailty as a phenotype, whereas others define frailty as an index of cumulative clinical deficits. Prevalence: 10%–60% of older adults depending on the CVD burden, and the tool and cutoff chosen to define frailty, as well. | ↑Risk from CVD and medical, device, percutaneous catheter, and surgical therapies, as well, 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, bedrest, 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 the population and methods, but it rises with age, generally in the range of 2%–5% in those 60–65 y old to >20%–40% in those ≥90 y old. 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 ≈5.0% of those 71–79 y old to 35%–40% of those ≥90 y old. | ↓Independence ↓Adherence ↓Shared decision-making ↓Quality of life ↑Hospitalization ↑Death | Often confounds assessments of symptoms. Often confounds accounts of present illness and past medical history. Often confounds adherence. Does not negate the potential value of therapeutic intervention, but it affects the decision and implementation process. |
| Delirium | Disturbance in cognition, attention, and consciousness or perception with fluctuating course. Can manifest as agitated state or quiet and withdrawn. High prevalence in older adults who are hospitalized, that is, ≈30%–60%. | ↑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 pain. Predisposing risks include cognitive deficit, sensory limitations, and disorienting medications. Treat by optimizing environment to increase orientation, avoid sedation, reduce medications, reduce pain. |
| Polypharmacy | Polypharmacy refers to multiple medications usually ≥5 chronic and concomitant use. May have unintended interactive effects (not required for definition). 40% of older adults take ≥5 medications. | ↑Adverse events (errors and drug interactions) ↑Rehospitalizations ↑Death | ↑Medication errors ↑Drug-drug and drug-body interactions ↓Adherence is common Under- and overtreatment both commonly occur Consider deprescribing |
| Disability | The inability to care for oneself or to manage one’s own home | ↑Risk progressive functional and cognitive declines ↓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 bedrest) can result in temporary immobility, delirium, disturbance in sleep pattern, and increase the risk of loss of independence. Suboptimal transitions are common contributors to disability (eg, hospital to home, and even hospital to post–acute care or hospital to home if support is inadequate or patient education has been deficient). |
| Sensory loss | Vision and hearing deficits are common | ↑Risk progressive functional and cognitive declines ↓Self-reliance and self-efficacy ↑Long-term care ↑Death | Same as disability |
CVD indicates cardiovascular disease.
Multimorbidity and Polypharmacy
Multimorbidity, defined as ≥2 chronic conditions, is ubiquitous in older adults with CVD.17 In Medicare fee-for-service beneficiaries with ischemic heart disease, 48% have ≥5 comorbid conditions, 32% have 3 to 4 coexisting conditions, 17.5% have 1 to 2 other conditions, and only ≈2.5% have isolated ischemic heart disease.25 Thus, ACS in older patients almost always occurs in the context of multiple comorbidities, many of which may intersect with the approach to treatment. In addition, high comorbidity burden is often associated with polypharmacy (usually defined as chronic use of ≥5 medications) and hyperpolypharmacy (usually defined as chronic use of ≥10 medications), which greatly increases the risk of adverse drug interactions and hospitalization.26,27 It has been estimated, for example, that patients taking ≥10 medications have >90% likelihood of having at least one clinically important drug-drug interaction. To mitigate the effect of multimorbidity and polypharmacy, it becomes important to consider treatment for ACS in the context of these competing risks and engage in a shared decision-making process with the patient and family to ensure that the approach to management is patient centered and aligned with the patient’s goals of care. A pharmacist with expertise in geriatric drug prescribing can provide guidance for discontinuing (ie, deprescribing) nonessential prescription and over-the counter medications, and nutraceuticals, as well, with goals to minimize the potential for drug-drug and drug-disease interactions and related susceptibilities to falls, confusion, and other age-related risks.28
Frailty
Frailty, characterized by physiological decline across multiple organ systems resulting in increased vulnerability to stressors, is associated with an increased risk for adverse health outcomes, including functional decline, institutionalization, and death.29,30 As noted earlier, older adults often have chronic low-grade inflammation (inflammaging), which represents a shared risk factor for frailty and CVD (Figure 1).15,31,32
In community-dwelling older adults, the prevalence of frailty increases from 16% at 65 to 69 years of age to ≈22.2% at 80 to 84 years of age.29 The prevalence of frailty is higher in women than in men.33 Commonly used tools to assess frailty include the Fried Frailty Index,34 Rockwood Clinical Frailty Score,35 and the Frail Scale.36 In addition, slow gait speed (<0.8 m/sec), as assessed by a 4- to 6-meter walk, has been shown to be a reliable surrogate for frailty in ambulatory older adults. Although there is still no consensus on the optimal method to assess frailty in ACS, there is consensus that this dimension of health status merits assessment as a criterion for clinical decisions in a manner that is at least standardized within each institution.6 It is often not feasible to assess frailty by gait speed or other performance metrics in the context of ACS management; alternative approaches are provided in the percutaneous coronary intervention (PCI) and surgical sections below.
Because frailty heightens risk for adverse outcomes in patients undergoing procedures, a less aggressive approach may yield superior outcomes. Given that frail patients are at high risk for functional decline during and after hospitalization,37 physical therapy and CR with progressive mobilization are also particularly important to consider early in the course of treatment (see Cardiac Rehabilitation in Older Adults). Likewise, outpatient CR and nutrition are key components of long-term ACS care. Future clinical trials and observational studies evaluating patients admitted with ACS must include older patients living with geriatric syndromes including frailty.
Cognitive Impairment
In the United States, the prevalence of mild cognitive impairment, a condition associated with increased risk for subsequent dementia, is ≈10% in people 70 to 79 years of age and ≈25% in those ≥80 years of age.38 The prevalence of Alzheimer disease, which accounts for 60% to 80% of dementia, increases from 5.3% at 65 to 74 years of age, to 13.8% at 75 to 84 years of age, and 34.6% after 85 years of age.39 Vascular cognitive impairment and dementia are also present in 5% to 10% of older adults and often coexist with other dementia types. Women are ≈50% more likely to develop dementia than men, and women account for nearly two-thirds of dementia cases in the United States. In addition, the prevalence of dementia is 2-fold higher in older African American individuals and 1.5-fold higher in older Hispanic American compared with White individuals. Although formal testing is required to establish a diagnosis of dementia, the Mini-Mental State Examination,40 Mini-Cog,41 and Montreal Cognitive Assessment42 are commonly used screening tools to identify individuals who may benefit from further evaluation.
In the setting of ACS, patients with mild cognitive impairment or dementia may experience deterioration in cognitive function relative to their baseline because of the stress of the acute event, the unfamiliar environment, or medication side effects. The medical history may be unreliable and decision-making capacity may be impaired. When feasible, relevant history and goals of care, including resuscitation status, should be reviewed with a surrogate historian. It is also important to clarify if the patient has an advance directive and durable power of attorney for health care.
Delirium
Delirium is an acute state of confusion characterized by a fluctuating course with alterations in attention, orientation, awareness of environment, cognition, and behavior. The incidence of delirium in hospitalized patients >65 years of age is ≈20% and increases to >70% among those requiring intensive care. Delirium is associated with increased risk for complications, longer length of stay, and higher likelihood of discharge to a post–acute care facility.43 Risk factors for delirium include older age, preexisting dementia, and certain psychoactive medications (especially benzodiazepines), which should therefore be avoided.44 Several screening tools are available, but the Confusion Assessment Method45 is the most widely used. Patients at increased risk for delirium should be identified (including all older patients admitted to intensive care), because up to 40% of incident delirium cases can be prevented by implementing a series of specific interventions. Management of delirium requires attention to all potential causes, nonpharmacological interventions, and judicious use of medications if necessary.44
Holistic Approach to Care
Given the complexity of disease management in older adults with ACS, optimal approaches to management usually entail care that is more individualized and patient-centered than among younger adults, because each patient’s unique set of circumstances has bearing on their sense of optimal outcomes. Comorbid medical and geriatric conditions, medications, preexisting functional status, patient preferences, and goals of care are among the issues that shape treatment decisions and extend beyond the parameters used in traditional disease-based ACS risk scores. In critically ill patients for whom an urgent therapeutic decision is required (eg, emergency PCI or surgery versus medical management), there may not be sufficient time to explore all relevant aspects of the patient’s situation, in which case clinicians must use assessments incorporating retrospective perspectives and best clinical judgment on the basis of the information at hand, including discussions with the patient, health care proxy, and family.46,47 In other cases requiring less urgent decision-making, a more considered approach, including a determination of what matters most to the patient, as a means to inform goals of care and therapeutic direction, coupled with shared decision-making, will likely yield outcomes that are most satisfying to the patient, health care proxy, family, and clinical care team. It is optimal to have an advance directive or a durable power of attorney for older patients before hospitalization for acute ACS event.
Considerations for Clinical Practice
1.
Geriatric syndromes are age-related physiological vulnerabilities that include multimorbidity, polypharmacy, frailty, functional decline (cognitive and physical), delirium, sensory decline (hearing, vision, and pain), and falls.
2.
Geriatric syndromes influence health outcomes for older patients with ACS, but ACS can also worsen the burden of preexisting geriatric syndromes.
3.
A holistic approach to ACS care is commensurate with the relatively more complex issues pertaining to ACS in older adults and includes an individualized and patient-centric approach to care, taking into consideration coexisting and overlapping health care domains.
Diagnostic and Disease-Based Classification of ACS in Older Adults
Clinical History and Examination
The first step in the evaluation of patients presenting with possible ACS, either in the emergency or office setting, is classification of symptoms.48 A comprehensive history captures the characteristics of chest pain or associated types of symptoms, including the nature, onset and duration, location, radiation, and precipitating or relieving factors. Nonetheless, in older adults, accounts of symptoms are more likely to be affected by multimorbidity, altered sensory capacities, and cognitive impairment, such that their diagnostic specificity and sensitivity are diminished. In a nationwide study of emergency department patients ≥80 years of age with chest pain, more than half were ultimately found to have a noncardiac cause of chest pain, 5.7% had decompensated heart failure, 7.8% had CAD without MI, and only 3.7% had an ACS.49 Thus, the vast majority of chest pain presentations do not represent ACS. ACS in older adults is also more likely to manifest with symptomology that is considered nonischemic in younger populations, including shortness of breath, syncope, or sudden confusion.50 In the prospective SILVER-AMI study (SILVER-AMI: Outcomes in Older Persons With Heart Attacks) of >3000 patients ≥75 years of age hospitalized with acute MI, 44% of patients did not report chest pain as their primary symptom, including 40% of patients presenting with STEMI. Women presenting with NSTEMI were less likely than men to report chest pain as a primary symptom (50.0% versus 58.6%; P<0.001).51 In another analysis from the SILVER-AMI cohort, cognitive impairment was present in 17% of participants.52 Women had a higher prevalence of cognitive impairment compared with men (NSTEMI: 20.6% versus 14.3%; P<0.001), posing challenges for timely presentation to the emergency department and the description and recall of symptoms.51 Heart failure, symptoms other than chest pain, and being Black or Hispanic American were also associated with delayed arrival at the hospital.53
The electrocardiographic (ECG) is a key step in initial evaluation for ACS. Most older adults (≈70%) in clinic and hospital settings have some form of abnormality on baseline ECG. These include LV hypertrophy (≈20%), conduction system disease (10% right bundle-branch block and ≈5% left bundle-branch block), paced rhythm (≈5%), or atrial fibrillation (≈12%).54 Such high prevalence of preexisting abnormalities on ECG often complicates interpretation of the presenting ECG in older patients with suspected ACS, and comparison with previous ECGs, when available, is essential. For older patients with nondiagnostic electrocardiographic presentations (eg, left bundle-branch block or paced QRS), a high level of suspicion for a diagnosis of ACS is needed, especially if older patients present with cardiac symptoms, unstable hemodynamics, or the typical rise and fall pattern of cardiac biomarkers. The physical examination for older adults with ACS may be informative of conditions that alter myocardial oxygen supply and demand, including hypoxia, tachycardia (eg, atrial fibrillation), hypotension, uncontrolled hypertension, or acute stressors such as an injurious fall, all contributors to type 2 MI. Aortic stenosis can be readily detected by physical examination and is a common confounder among patients with angina.
Because of the inherent complexities in older patients presenting with suspected ACS, the initial history, physical examination, and ECG alone often do not confirm or exclude the diagnosis. However, the initial evaluation can stratify those with possible ACS presentations into low, intermediate, or high risk to better inform the initial approach to care and interpretation of biomarker testing (Figure 2).55 Although the Fourth Universal Definition of MI is widely used, it is often not ideal for guiding risk stratification in older patients with chest pain or ACS. There is a need for refinements to estimate overall prognosis that incorporate concomitant (and biologically related) aging phenomena that exacerbate risk (reduced longevity, and greater disability, as well) when present (eg‚ frailty, sarcopenia, multimorbidity). Older patients living with geriatric syndromes and presenting with NSTEMI are at increased risk for hospital-associated complications. Characteristics that predict higher risks of complications requiring admission to the ICU in older patients include heart failure, initial heart rate, systolic blood pressure, initial troponin, initial serum creatinine, previous r evascularization, chronic lung disease, ST-segment depression, and age.56 The ACTION (Acute Coronary Treatment and Intervention Outcomes Network) ICU risk score can be a helpful guide for disposition of older patients into the cardiac ICU versus intermediate care units.56 The ACTION ICU risk score included patients ≥65 years of age in the ACTION registry with a median (interquartile range) age of 77 (71–84) years.
Sex-Related Differences in ACS
Although men constitute the majority of ACS encounters, the proportion of women in the ACS population increases with age from 20% to 25% among patients <50 years of age to ≈50% among older adults >80 years of age.57,58 These patients tend to be described in practice as older and sicker, highlighting the sex-related differences among men and women.59 The burden of cardiovascular risk factors among older women is higher than among older men, including hypertension and diabetes, and older women may be more likely to have a previous heart failure or heart failure with preserved ejection fraction, but not heart failure with reduced ejection fraction.59 In the Italian Elderly ACS collaboration (Early Aggressive Versus Initially Conservative Therapy in Elderly Patients With Non-ST-Elevation Acute Coronary Syndrome), older women had a higher prevalence of cardiovascular risk factors, including diabetes, and noncardiovascular comorbidities, including kidney dysfunction,60 whereas older men had a longer duration of coronary disease, history of MI, revascularization, and more complex anatomic disease.60 Symptoms like nausea or abdominal pain are more common among women, and pain in the jaw, neck, or back are also frequently observed. Weakness, dyspnea, or total lack of pain (silent ischemia) may affect interpretation of symptoms and result in delays in presentation. These issues can result in poor outcomes attributable to delays in implementation of reperfusion therapies. In the LADIES ACS study (LADIES Acute Coronary Syndromes), the Gensini score, a surrogate for CAD severity, was higher in men than in women at all ages.61 In the CURE trial (Clopidogrel in Unstable Angina to Prevent Recurrent Events), high-risk women with ACS underwent less coronary angiography, less coronary artery bypass graft (CABG) surgery, and had a higher incidence of major adverse cardiovascular events (MACE) outcomes including recurrent MI, stroke, and refractory angina.62 These sex-related differences should trigger improvement in quality of care for older women presenting with ACS.
Biomarkers (High Sensitivity Cardiac Troponin and N-Terminal Pro-B Type Natriuretic Peptide)
The addition of high-sensitivity troponin (hs-Tn) provides important diagnostic sensitivity for the presence of ACS in older adults, but that comes at the expense of reduced specificity, in particular, among older adults with underlying kidney disease.63,64 high-sensitivity cardiac troponin (hs-cTn) assays are the standard of care for identifying myocardial injury, although questions remain about whether minimal elevations, which carry prognostic value, are actionable in a manner that improves outcomes.65 If the hs-cTn continues to rise, the biomarker is helpful in identifying the underlying cause of the injury and indicating myocardial ischemia. Chronic elevations of hs-Tn levels are associated with replacement fibrosis and progressive changes in LV structure that are common in the older population.66 Fluctuations in the levels of hs-Tn are also associated with age-related decline in kidney function (especially in the context of ACS), hormonal changes (menopause in women), and age-related changes in body composition.65,67 For this reason, evaluating patterns of rise and fall of hs-Tn is essential.67 Independent determinants of higher levels of troponin in asymptomatic populations include older age, male sex, diabetes, lower estimated glomerular filtration rate, LV mass, Black race, hypertension, sarcopenia, and history of heart failure. Therefore, many asymptomatic older adults live with biomarkers that fluctuate or are persistently above the diagnostic thresholds for MI. Population studies such as the Dallas Heart Study, ARIC (Atherosclerosis Risk in Communities,) and Cardiovascular Health Study demonstrate that the proportion of hs-Tn above the 99% upper reference limit is upward of 19% to 28% (depending on vendor) in asymptomatic individuals >75 years of age.
Classification of Myocardial Injury
MI is defined as myocardial cell death attributable to a prolonged period of inadequate oxygen supply to the myocardium. All types of myocardial infarction or injury are more common in older adults. The taxonomies for myocardial injury include acute nonischemic myocardial injury identified by a rise and fall of hs-Tn without a primary ischemic cause and chronic myocardial injury identified by persistent elevations of hs-Tn above the 99th upper reference limit over time. Type 1 MI is caused by atherothrombotic CAD, usually the result of plaque rupture. Type 2 MI is caused by a mismatch between oxygen supply and demand and indicates myocardial stress related to another condition (ie, not attributable to plaque rupture). Older adults are predisposed to type 2 MI, in part, because of an age-related decline in endothelium-mediated coronary vasodilation and resultant impaired ability to increase coronary blood flow in response to increased myocardial oxygen demand.17 Type 2 MI is particularly common in older adults admitted with comorbid conditions such as hypotension (eg, attributable to sepsis), uncontrolled hypertension, chronic obstructive pulmonary disease, pneumonia, acute anemia, heart failure exacerbations, or CKD.68 Among patients with type 2 MI, the incidence of recurrent type 2 MI at 5-year follow-up was 9.7%, compared with 1.7% 5-year incidence of type 1 MI.68 The survival prognosis among patients with type 2 MI is also determined by the underlying cause for the supply-demand mismatch, with arrhythmia having a more favorable prognosis than hypotension, anemia, or hypoxia. Adjusted long-term death after type 2 MI is markedly higher than after type 1 MI (52% versus 31% at 5 years), driven by early noncardiovascular death.68 Patients with myocardial injury are also at increased risk for future cardiovascular events irrespective of pathogenesis.
Coronary Computed Tomography Angiogram for Risk Stratification
Whereas coronary angiography has traditionally been regarded as the most definitive means to assess for CAD, it is associated with relatively greater risks in older adults. After MI has been ruled out by troponin, a coronary computed tomography angiogram (CCTA) is a less invasive way than coronary angiography to exclude obstructive CAD in patients with intermediate or undetermined risk. CCTA can visualize the extent and severity of nonobstructive and obstructive CAD, and atherosclerotic plaque composition and high-risk features, as well (eg, positive remodeling, low attenuation plaque). Calculation of fractional flow reserve with computed tomography may provide an estimation of lesion-specific ischemia. Clinicians may be able to use CCTA for triaging patients with suspected ACS by looking for features of high-risk plaque, but the reliability of the test is somewhat diminished, in particular, in very old patients.69 High-risk plaque characteristics on CCTA may assist in identifying culprit lesions of ACS.70 When evaluating older adults for CCTA, the use of contrast (typically 50–100 mL) must be considered, especially given the age-related vulnerabilities of acute and chronic kidney disease. The heart rhythm must be regular (ie, not atrial fibrillation or atrial arrhythmia) with rate preferably <70 beats per minute. Heavily calcified coronary arteries in older patients may render interpretation of lesion severity difficult, and motion artifact (eg, if patient is delirious) can obscure interpretation. Downstream testing is also a relevant consideration because CCTA may lead to additional testing that diverges from a patient’s goals and preferences.
Considerations for Clinical Practice
1.
ACS represents a small proportion of all chest pain presentations in younger and older adults. ACS presentations without chest pain, such as shortness of breath, syncope, or sudden confusion, are more likely to occur in older adults.
2.
hs-cTn assays are standard of care for identifying acute and chronic myocardial injury. Many older adults have persistent elevations attributable to myocardial fibrosis and CKD that lessen the positive predictive value. For this reason, evaluating patterns of rise and fall is essential.
3.
Myocardial injury can be classified in 4 subtypes: acute nonischemic injury, chronic myocardial injury, MI (type 1), and myocardial infarction (type 2). All types are more common in older than in younger adults.
Guideline-Directed Medical Therapy for ACS In Older Adults
Pharmacodynamics and Pharmacokinetics
With aging, multiple physiological changes affect both the pharmacokinetics and pharmacodynamics of many medications used for ACS. Older adults can exhibit reductions in kidney function, hepatic blood flow, and muscle mass with an increase in body fat that in turn affects the absorption, distribution, metabolism, and elimination of certain guideline-directed medical therapies (Figure 3).71 These physiological changes greatly affect the pharmacokinetics of orally administered medications that must undergo dissolution to be absorbed by the gut, then undergo first-pass hepatic metabolism before entering the systemic circulation, and then potentially be renally eliminated. For intravenously administered medications, first-pass metabolism is bypassed, but protein binding and elimination can be altered.6 With a reduction in P-glycoprotein and cytochrome P450 isoenzymes, the potential exists for elevated serum concentrations of anticoagulants (warfarin, apixaban, dabigatran, and rivaroxaban), β-adrenergic blockers (carvedilol), and statins (atorvastatin, simvastatin). Anticoagulants (bivalirudin, eptifibatide, tirofiban, enoxaparin, fondaparinux), and all the oral direct anticoagulants, as well, are eliminated renally and doses must be adjusted according to the patient’s glomerular filtration rate.72,73 Because older adults may exhibit altered plasma protein concentrations, primarily attributable to underlying comorbid conditions, medications that are highly protein bound (eg, >90%), such as warfarin, heparin, amiodarone, lidocaine, furosemide, bumetanide, and nicardipine, and all statins except pravastatin can exhibit higher free concentrations with the potential for greater distribution, which may accentuate the risk for toxicity.6,74
Low body weight and lean mass are common in many older adults with ACS, which can affect medication dosing to avoid adverse events. Based on US package labeling, in patients <60 kg, a lower maintenance dose of prasugrel (5 mg daily) should be considered to reduce the risk of bleeding.75 In the case of apixaban, dosing adjustment is warranted if a patient meets 2 of the following: age ≥80 years, body weight ≤60 kg, or a serum creatinine ≥1.5 mg/dL.73 For dabigatran, observational studies suggest increased dabigatran-induced bleeding at low body mass indexes (<23.9 kg/m2), and, although no conclusive consensus exists regarding rivaroxaban dosing in patients weighing <60 kg, increased systemic exposure in cachectic patients has been suggested.73 Last, body weight is critical when dosing many intravenous antiplatelet medications such as the glycoprotein IIb/IIIa inhibitors (eptifbatide and tirofiban), prasugrel, and cangrelor, and unfractionated heparin, low-molecular-weight heparins (enoxaparin and dalteparin), and the factor Xa inhibitor fondaparinux, as well.72
From a pharmacodynamic perspective, adaptive and structural vascular and myocardial changes attributable to aging can lead to exaggerated response to certain medications.12 Diminished carotid sinus baroreceptor sensitivity, and a slowing of both sinus node activity and atrioventricular conduction, as well, can increase the risk of bradycardia with β-adrenergic blockers, nondihydropyridine calcium channel blockers, and amiodarone. With an increase in arterial and ventricular stiffness, older adults may become preload sensitive, leading to a greater risk of hemodynamic lability from vasodilator therapies and diuretics.6,76
Pharmacotherapy for ACS in Older Adults
Medical therapy for ACS in the older adult, in general, is similar to that in younger patients but needs to take into consideration the increased atherothrombotic risk, higher bleeding risk compared with younger patients in the context of the physiological changes described earlier, and prevalent geriatric syndromes. As such, risk versus benefit assessments, tailored to each individual, guide the use and dosing of ACS therapies. Therapies initiated in the hospital should be evaluated on a recurring basis during outpatient follow-up with escalation of treatment as needed to reduce overall cardiovascular risk, but also de-escalation or deprescribing as needed to relieve or prevent side effects in the context of patients’ goals and preferences.28
Although both clopidogrel and ticagrelor are recommended for older patients with ACS in the recent revascularization guidelines,77 clopidogrel may be the preferred P2Y12 inhibitor in older patients because it carries a lower bleeding risk profile compared with ticagrelor. In the Elderly ACS 2 trial (The Elderly ACS II Trial), prasugrel did not show superiority over clopidogrel in the primary end points of death, MI, disability, stroke, rehospitalization, or bleeding among older patients.78 However, the bleeding rate was numerically higher in the prasugrel group.78 In the POPular 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) that enrolled older patients with non–ST-segment–elevation ACS, clopidogrel had an efficacy similar to ticagrelor in reducing MACE events and had fewer bleeding events.79 In the recent SWEDEHEART study (Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies), patients ≥80 years of age with MI who were discharged alive with aspirin combined with either clopidogrel or ticagrelor were evaluated. Older patients treated with ticagrelor did not have lower risk for the combined outcomes of death, MI, or stroke, but these patients had a 32% higher risk of bleeding.80 A network metanalysis (n=14 485) comparing clopidogrel, prasugrel, and ticagrelor in older adults with ACS has been recently published and showed that clopidogrel has the most favorable profile for reducing bleeding events.81 Although the benefit of ticagrelor over clopidogrel was consistent across age groups, there was a significantly higher risk of major bleeding in ticagrelor-treated older patients.82 Furthermore, there is a black box warning on the use of full-dose prasugrel of 10 mg/d in patients >75 years of age because of the increased risk of serious bleeding. Limited evidence exists for P2Y12 inhibitor switching. In older patients at high risk of both thrombosis and long-term bleeding, higher potency P2Y12 inhibitors, such as ticagrelor or reduced dose (5 mg) prasugrel, may be superior in the first month after PCI for ACS, then transitioning to clopidogrel for long-term bleeding risk reduction.83 If more potent dual antiplatelet therapy (DAPT) is used in older patients, DAPT de-escalation by switching from more potent drugs (eg, ticagrelor or lower-dose prasugrel) to clopidogrel can be considered 30 days after the initial ACS event or guided by platelet function testing, because a switch within the first 30 days after index admission may increase the risk of ischemic events.84–86
β-Blockers may be of particular benefit because of their anti-ischemic effects and influence on the burden of arrhythmia in the setting of acute myocardial ischemic injury. However, cautious dosing is warranted along with vigilance for bradycardia and incident heart failure in the acute setting, and chronotropic incompetence and fatigue during chronic management, as well. In patients with severe asymptomatic bradycardia (heart rate <40 beats/min), reduction or cessation of β-blockade and other nodal agents is preferred to see if pacemaker implantation can be avoided. In a large observational study of patients >65 years of age who were >3 years post-MI, no association between β-blocker use and long-term cardiovascular outcomes was observed, suggesting that deprescribing may be considered at that time.87
A recent meta-analysis confirmed that low-density lipoprotein cholesterol lowering had similar efficacy in reducing the risk of cardiovascular death, ACS, stroke, or coronary revascularization in patients more than and less than 75 years of age; the results were also consistent across trials of statins, ezetimibe, and PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors. Although postmarket reports have raised concern for cognitive impairment, particularly in the aging population, most recent data have shown that there is no effect of statins or PCSK9 inhibitors on patient-reported cognition even with very low low-density lipoprotein levels.88 Furthermore, randomized trials of statins,89 ezetimibe,90 and PCSK9 inhibitors91 have not observed between-group differences in cognitive function. Studies with longer-term follow-up of PCSK9 inhibitor treatment are needed. Moderate- or high-intensity statin therapy is recommended for patients >75 years of age with clinical atherosclerotic CVD.92 Myalgias can be dose dependent in older adults and influence mobility and quality of life, particularly among patients of Asian descent. Careful attention to statin dosing, dietary intake, and drug-drug interactions will allow older adults to benefit from secondary-prevention lipid lowering effectively and safely.
Drugs targeting the renin-angiotensin-aldosterone system, namely angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers, and aldosterone antagonists, have been associated with death benefit in patients who have ACS with large infarcts and LV dysfunction.93 Of note, in patients with heart failure with reduced ejection fraction, low dose compared with higher doses of lisinopril, losartan, and sacubitril valsartan showed no difference in death, thus suggesting that lower doses of these agents may be beneficial, particularly in patients with renal and hemodynamic vulnerabilities.94–96 These are often underused in older patients with ACS because of clinician concerns regarding expected benefit in the face of shorter life expectancy and potential complications (eg, syncope, hyperkalemia, or worsening kidney function) of treatment. When possible, shared decision-making is important, and kidney function, blood pressure, and potassium levels are best monitored within the first 12 weeks of initiation, with each dose increase and on a yearly basis thereafter. Dose reduction or drug discontinuation may be needed for severe or symptomatic hypotension, hyperkalemia, or persistent >30% creatinine increases.97 Recent data suggest that ACE inhibitors/angiotensin II receptor blockers that cross the blood-brain barrier (ACE inhibitors: captopril, fosinopril, lisinopril, perindopril, ramipril, and trandolapril; angiotensin II receptor blockers: telmisartan, and candesartan) were associated with better memory recall at 3 years than those that did not.98 The use of angiotensin receptor-neprilysin inhibitor versus ACE inhibitors to reduce MACE events after MI was investigated in the PARADISE-MI trial (Prospective ARNI versus ACE Inhibitor Trial to Determine Superiority in Reducing Heart Failure Events After MI).99 In that study, more than one-third of the patients were >70 years of age, but only 24% were women. The primary outcome of death, first heart failure hospitalization, or outpatient heart failure was not different between the angiotensin receptor-neprilysin inhibitors versus ACE inhibitors (11.9 versus 13.2; P=0.17).100
Pharmacological Management of Atrial Fibrillation in the Context of ACS
Older adults are at higher risk for recurrent thrombotic events, and they may derive the most benefit from appropriately dosed anticoagulation therapy. The prevalence of atrial fibrillation increases with age and concomitant anticoagulation therapy increases bleeding risk. Among older adults in sinus rhythm treated with PCI for ACS, 1 to 4 weeks of triple anticoagulation therapy (aspirin, clopidogrel, and a direct oral anticoagulant) is recommended, followed by up to 1 year of clopidogrel and direct oral anticoagulant, after which direct oral anticoagulant monotherapy is continued.101 For patients with chronic atrial fibrillation undergoing PCI for ACS, double antithrombotic therapy is superior to a strategy of triple therapy. This is achieved using a direct oral anticoagulant and a P2Y12 inhibitor, preferably clopidogrel without aspirin.102 In older patients at increased thrombotic risk with acceptable bleeding risk, it is reasonable to continue triple therapy, including aspirin for 1 month after PCI.103 Double therapy is continued for 6 to 12 months, after which discontinuation of antiplatelet therapy is achieved, and treatment with oral anticoagulation therapy alone is maintained thereafter.103
Enhanced communication between the hospital cardiology team and outpatient cardiology team (eg, cardiologist, nurse practitioner, or physician assistant) caring for the older patient is critical to coordinate the medication regimen and to provide the rationale for long-term care. With this alignment between clinicians, older adults, particularly those with mobility or cognitive difficulties, may benefit from more simplified medication and dosing regimens than one that checks all the guideline indication boxes. Once-daily medications are often more conducive to adherence but require careful assessment of potential interactions when multiple drugs are taken together. Although within class medication switches or dosing changes can occur after discharge from an ACS hospitalization, 90-day prescriptions are often feasible and have been shown to improve post-ACS medication adherence.104 Facilitating medication supplies in other ways, such as using mail-order pharmacies,105 can make a big difference in long-term evidence-based medication persistence of older adults after ACS.
Considerations for Clinical Practice
1.
In the older patient with ACS, clopidogrel is the preferred P2Y12 inhibitor because of a significantly lower bleeding profile than ticagrelor or prasugrel, but for patients with STEMI or complex anatomy, the use of ticagrelor is reasonable.
2.
In patients with chronic atrial fibrillation undergoing PCI for ACS, the duration of triple therapy should be minimized, with discontinuation of aspirin and transition to dual antithrombotic therapy with clopidogrel and a new oral anticoagulant, ideally within 4 weeks of PCI.
3.
Therapies initiated in the hospital are best evaluated on a recurring basis during outpatient follow-up with escalation of treatment as needed to reduce cardiovascular risk, but also de-escalation or deprescribing to relieve or prevent side effects.
4.
Older adults, particularly those with mobility or cognitive difficulties, may benefit from relatively simpler medication and dosing regimens than those commonly indicated by existing guidelines. Comorbidities, geriatric syndromes, and personal health care goals and preferences are also relevant factors to integrate within tailored regimens of care.
Percutaneous Revascularization in Older Adults
The management for STEMI in older adults follows the same general principles as for younger patients. The indication for primary PCI in older adults presenting with STEMI should consider STEMI-related variables, including delay in presentation, extent of electrocardiographic changes, and LV dysfunction, and patient-related variables, including severe comorbidity, severe cognitive impairment, and limited life expectancy. Barring these end-stage disease processes, primary PCI is safe and effective even among patients with very advanced age, as long as it is aligned with their preferences of care.106,107 For older patients with NSTEMI, cardiovascular and noncardiovascular risk evaluation before revascularization are critical elements to achieve optimal outcomes, both in respect to cardiovascular (eg, symptom control and low bleeding risk)108 and noncardiovascular (eg, function, independence, quality of life, and overall well-being).
Cardiovascular Risk Evaluation for PCI
The American College of Cardiology/AHA guideline recommends risk stratification of patients with suspected NSTEMI to determine the choice of management, for example, through the use of risk assessment scores such as TIMI (Thrombolysis in Myocardial Infarction) risk score and GRACE risk score.77 The GRACE score is heavily age-weighted,109,110 leading to older adults with NSTEMI being classified as high risk, warranting consideration of early invasive therapy. Type 2 MI is frequently observed in older adults,111 and the GRACE risk score provides only moderate discrimination of death risk for those with type 2 MI.112 The baseline risk of bleeding during NSTEMI care among older adults is increased compared with younger patients, and the CRUSADE bleeding score has the best discriminative function for in-hospital major bleeding across all postadmission treatments.113 These risk scores do not take into account characteristics that are especially prevalent in older adults, such as frailty, multimorbidity, polypharmacy, and cognitive dysfunction. The relationship between frailty and risk of adverse outcome after STEMI and NSTEMI has been demonstrated in many studies using different frailty assessment tools.114–116
Among patients with NSTEMI, the composite outcome of MI, need for urgent repeat revascularization, stroke, significant bleeding, and all-cause death at 1 year occurred in more frail patients than in robust patients (39% versus 18%; hazard ratio, 2.79 [95% CI, 1.28–6.08]).117 In a systematic review and meta-analysis, frailty was associated with a severalfold increase in the adjusted risk of death for patients with STEMI (hazard ratio, 6.51 [95% CI, 2.01–21.10]) and NSTEMI (hazard ratio, 2.63 [95% CI, 1.51–4.60]).118 Multimorbidity is increasingly prevalent in the older population, particularly in those presenting with ACS. Comorbidity burden, as measured by the Charlson Comorbidity Index, predicts in-hospital and 1-year death in patients with ACS and is independently associated with adverse short-, medium-, and long-term outcomes after PCI.119,120 In another study,121 in older adults with non–ST-segment–elevation ACS referred for coronary angiography, the presence of multimorbidity was associated with an increased risk of long-term adverse cardiovascular events, driven by a higher risk of all-cause death. On average, each additional Charlson Comorbidity Index comorbidity was associated with a 31% increased adjusted risk of all-cause death at 5 years.121
Undiagnosed cognitive impairment is common in older patients with NSTEMI undergoing coronary angiography, and these patients are more likely to experience adverse events at 1 year.122 Although the optimal risk indices for older adults with ACS remain undefined, considerations of frailty, cognition, and comorbidity are critical perspectives to foster in respect to guiding optimal care, particularly for prognostic stratification, and identifying those who are most, and least likely, as well, to benefit from early invasive therapy. There is a need for refinements of standard risk scores to estimate ischemic and bleeding risks for older patients with ACS.
Geriatric and Patient-Centric Outcomes for the Older ACS Populations
Although the older adult population is rapidly expanding, these patients do not represent a homogeneous group. They differ on the basis of the presence or absence of frailty, comorbidities, physical or functional limitations, and social status when presenting with ACS.123 Older patients living with a greater burden of geriatric syndromes are more likely to develop disability, loss of independence, and impairment in quality of life and ability to self-care after an ACS event. When managing older patients presenting with ACS, the goals of care should extend beyond traditional cardiovascular outcomes, including MI, need for urgent and repeat revascularization, stroke, significant bleeding, and all-cause death. Assessment of patient-centric goals and outcomes necessarily remains with a focus on quality-of-life outcomes.124 Other key outcomes for older patients are the ability to live independently and to return to their previous environment and lifestyle. For older patients with a high burden of geriatric syndromes or with terminal cardiovascular illness, goals like days at home and other personal preferences that maximize quality of life should be prioritized as important outcomes for guiding ACS management.124 With these considerations in mind, the most recent clinical trial designs in older frail patients with ACS included secondary outcomes like functional capacity, instrumental activities, cognitive capacity, and quality of life during follow-up compared with baseline.125 It should be noted that issues of senescence, inflammation, and other hallmarks of aging are variable from person to person, thus adding to the heterogeneity of older adults.
Key Points
1.
When managing older patients presenting with ACS, the goals of care should extend beyond traditional cardiovascular outcomes to include patient-aligned goals and preferences that maximize quality-of-life outcomes.
2.
For older patients with ACS at the end of life, goals like “days spent at home in the past 6 months of life” and relief of pain and discomfort are important metrics for quality care.
Correlation Between Frailty and Coronary Anatomical Complexity
Frail adults presenting with NSTEMI have more procedurally challenging angiographic findings independent of age (ie, severe culprit lesion calcification, high SYNTAX scores, high-risk lesions). In 1 study, frail patients had >5-fold increase in odds of severe culprit lesion calcification when compared with robust patients (unadjusted odds ratio [OR], 5.40 [95% CI, 1.75–16.8]; P=0.03).126 Frail patients also had a greater prevalence of high-risk lesions on intravascular ultrasound imaging, with a 2.81 increased adjusted odds (95% CI, 1.06–7.48; P=0.039) of presence of thin-cap fibroatheroma.127 During follow-up, frail older adults who underwent angiography for NSTEMI were at increased risk of all-cause death, unplanned revascularization, MI, stroke, and bleeding.128
Timing of Invasive Strategy
The current revascularization guidelines describe high-risk groups that may benefit from an early invasive approach, which results in lower rates of death, MI, or refractory angina during follow-up. Older patients with ACS are disproportionately affected with high-risk features favoring an early invasive approach to management. The GRACE score has been used to estimate the risk of death attributed to ischemic burden in patients with ACS. A GRACE score of >140 indicates a high-risk patient group that benefits from revascularization within 24 hours, resulting in a lower incidence of recurrent ischemia, need for revascularization, and shorter hospital length of stay.77 For patients ≥75 years of age, ST-segment deviation on ECG coupled with elevated hs-Tn levels yields a GRACE score of >140, categorizing them as high risk. When more precarious conditions coexist, the risk of death and MACE increases significantly. These conditions include the presence of cardiogenic shock, refractory angina, and hemodynamic or electrical instability, which require an immediate invasive assessment (preferably within 2 hours) to provide information on the extent and severity of coronary disease, hemodynamics, LV function, and suitability for revascularization.77 However, other factors, including patient’s preferences and burden of geriatric syndromes that may affect life expectancy, must be taken into account when considering immediate revascularization strategies in older patients.
Key Points
1.
Older patients with ACS are often high risk (GRACE score >140) and should be considered for an early invasive approach to reduce the incidence of recurrent ischemia and the need for revascularization, and to shorten hospital length of stay.
2.
When cardiogenic shock, refractory angina, and hemodynamic or electrical instability are present, an immediate invasive approach may be associated with improved outcomes.
3.
Patient preferences and geriatric syndromes affecting life expectancy must be considered when deciding on an invasive versus conservative approach to ACS management.
Timing of DAPT Therapy
The use of DAPT is critical in the medical management of ACS because of its role in reducing ischemic and thrombotic complications. For older patients being considered for immediate or early invasive therapy, a loading dose of nonenteric coated aspirin 325 mg, followed by a daily dose of 81 mg is recommended before invasive assessment to reduce ischemic risks. Available P2Y12 inhibitors include clopidogrel, ticagrelor, and prasugrel. Of these, clopidogrel and ticagrelor are most commonly used in older patients with ACS, because prasugrel is associated with adverse outcomes, including major bleeding in the older adult populations. The timing of the loading dose of P2Y12 inhibitors remains an area of debate, but a strategy of introducing the loading dose after the anatomy is known was recently endorsed by the American College of Cardiology/AHA/Society for Cardiovascular Angiography and Interventions revascularization guidelines. This should be followed by daily dose to reduce ischemic events.77 This strategy seems most reasonable because of the need to discuss approach to revascularization with the Heart Team and whether surgical evaluation is needed.
Key Points
1.
A loading dose of aspirin 325 mg followed by a daily dose of 81 mg should be given before an invasive approach to management to reduce ischemic events.
2.
A loading dose of a P2Y12 inhibitor should be given after the anatomy is known in patients proceeding to PCI. A P2Y12 inhibitor should be withheld in patients for whom cardiac surgery is being contemplated.
Efficacy of Percutaneous Revascularization in Older Adults
Non–ST-Segment–Elevation Myocardial Infarction
To date, of the 5 randomized clinical trials specifically investigating an invasive strategy in older patients with NSTEMI, 4 have found no benefit of invasive treatment on the primary end point compared with conservative management,130–133 whereas the other showed that an invasive strategy reduced recurrent MI and urgent repeat revascularization (Table 3).134,135 The Italian Elderly ACS trial randomly assigned patients ≥75 years of age with non–ST-segment–elevation ACS to early invasive versus initially conservative strategy. The trial did not report geriatric syndromes including frailty and multimorbidity.130 Patients randomly assigned to the initially conservative strategy had higher rates of ischemic events during index hospitalization, which prompted urgent angiography. Although there was a 20% reduction in the rate of death, reinfarction, disability, stroke, or rehospitalization, this reduction was not statistically significant because the trial was powered to detect a 40% difference in event rates. Patients with elevated troponins who were randomly assigned to the early invasive group showed a significant 57% reduction in the primary end point on subgroup analysis.130 The After Eighty Study (2016) randomly assigned patients ≥80 years of age with NSTEMI or unstable angina to an invasive versus conservative strategy.134 Similar to the Italian Elderly ACS study, frailty or other geriatric syndromes were not explicitly reported. During a median follow-up of 18 months, the invasive strategy was found to be superior to the conservative strategy in reducing MI, urgent revascularization, and stroke (41% versus 61%; OR, 0.48 [95% CI, 0.37–0.63]; P<0.001).134 The MOSCA trial randomly assigned patients ≥70 years of age with higher comorbidity burden to invasive versus conservative strategy for NSTEMI. Although there were numerically fewer primary end point events (death, reinfarction, or cardiac readmission) in the invasive arm, the difference did not reach statistical significance.131 This study was followed by the MOSCA-Frail trial (The Invasive and Conservative Strategies in Elderly Frail Patients With Non-STEMI), which was recently terminated (Table 3). Other smaller trials also did not show benefit of an early invasive strategy but were underpowered to detect clinically meaningful differences.132,133 The larger British Heart Foundation SENIOR-RITA Trial (The British Heart Foundation Older Patients With Non-ST Segment Elevation Myocardial Infarction Randomized Interventional Treatment Trial) is currently randomly assigning patients ≥75 years of age with type 1 NSTEMI to either invasive or conservative treatment strategy. With an anticipated enrollment of 1668 older participants, this trial is poised to inform practice in older patients who have NSTEMI living with geriatric syndromes (ClinicalTrials.gov; Identifier: NCT03052036). Using both observational and randomized data, systematic reviews and meta-analyses have shown a likely reduction in MI and recurrent revascularization associated with an invasive strategy, but no survival benefit and a higher risk of bleeding relative to a conservative strategy.139,140 More recently nonrandomized data from the SENIOR-NSTEMI study showed a survival advantage associated with invasive strategy among patients >80 years of age.141 Thus, the value of an invasive strategy in the management of patients ≥75 years of age remains uncertain, and additional studies are needed.
| Study | Population | Primary outcome | Frailty | Comorbidity |
|---|---|---|---|---|
| Savonitto et al Italian Elderly ACS (2012)130 | n=313 NSTEACS ≥75 y old | No difference in death, reinfarction, disabling stroke, repeat hospital stay for cardiovascular causes and severe bleeding at 1 y. Early invasive versus initially conservative; 27.9% versus 34.6%, HR, 0.80 (95% CI, 0.53–1.19); P=0.26. | No frailty assessment | No assessment of comorbidity burden or severity |
| Tegn et al After Eighty (2016)134 | n=457 NSTEACS ≥80 y old | Reduction in death, reinfarction, need for urgent revascularization and stroke at 18 mo, driven by lower rates of reinfarction and urgent repeat revascularization. Early invasive versus conservative; 41% versus 61%, HR, 0.53 (95% CI, 0.41–0.69), P=0.0001. | No frailty assessment | No assessment of comorbidity burden or severity |
| Sanchis et al MOSCA (2016)131 | n=106 NSTEMI ≥70 y old | No difference in death, reinfarction, or readmission for cardiac causes at 2.5 y. Invasive versus conservative; HR 0.77 (95% CI, 0.48–1.24), P=0.285. | No frailty assessment | Participants had at least 2 comorbidities. Comorbidity burden or severity assessed with Charlson Comorbidity Index. Findings not stratified by Charlson Comorbidity Index score or comorbidities. |
| MOSCA-Frail (2019)125 | n=167 frailty and NSTEMI, randomized to routine invasive (n=84) or conservative (n=84) | The primary end point: Number of days alive out of the hospital from discharge to 1 y. The coprimary end point: Composite of cardiac death, reinfarction, or postdischarge revascularization. Secondary end points: functional capacity, instrumental activities, cognitive capacity, quality of life at 6 mo. Terminated recently (unpublished data). Personal communication with Dr Juan Sanchis Forés, November 2, 2022. No benefit of invasive strategy on primary or coprimary end points. | Clinical Frailty Scale score ≥4 | Comorbidity burden and total number of drugs used (polypharmacy) |
| Hirlekar et al (2020)133 | n=186 NSTEACS ≥80 y old | No difference in all-cause death, reinfarction, stroke, urgent revascularization, or rehospitalization for cardiac causes at 1 y. Invasive versus conservative; 34.3% versus 37.7%, HR, 0.90 (95% CI, 0.55–1.46), P=0.66. | Frailty assessed with the Canadian Study of Health and Aging Clinical Frailty Scale. Low prevalence of frailty. Findings not stratified by frailty status. | No assessment of comorbidity burden or severity |
| De Belder et al RINCAL (2021)132 | n=251 NSTEMI ≥80 y old | No difference in all-cause death or reinfarction at 1 y. Routine invasive versus selective invasive; 18.5% vs 22.2%, HR, 0.79 (95% CI, 0.45–1.35), P=0.39. | No frailty assessment | No assessment of comorbidity burden or severity |
ACS indicates acute coronary syndromes; HR, hazards ratio; NSTEACS, non–ST-segment–elevation acute coronary syndrome; and NSTEMI, non–ST-segment–elevation myocardial infarction.
ST-Segment–Elevation Myocardial Infarction
In the context of STEMI, a pooled analysis of the TRIANA (Thrombectomy in Andalucia Using Aspiration), SENIOR-PAMI (Primary Angioplasty Versus Thrombolytic Therapy for Acute Myocardial Infarction in the Elderly), and Zwolle (The Zwolle Transmural Integrated Care for Cardiovascular Risk Management Study) trials showed a significant reduction in the risk of a composite outcome of death, reinfarction, or disabling stroke (OR, 0.64 [95% CI, 0.45–0.91]; P=0.013) with primary PCI compared with fibrinolysis.142 In a meta-analysis, patients 70 to 80 years of age who were randomly assigned to primary PCI had reduced all-cause death (OR, 0.55 [95% CI, 0.39–0.76]), reinfarction (OR, 0.37 [95% CI, 0.23–0.62]), stroke (OR, 0.36 [95% CI, 0.20–0.68]), and a composite of all 3 end points (OR, 0.45 [95% CI, 0.34–0.59]).143 The superiority of primary PCI over fibrinolysis appears to extend to older patients, although trials have been small, affected by slow recruitment, and findings are limited in the very old cohort, with no evaluation of frailty or comorbidity included. However, the results also suggest that fibrinolysis may be safe and effective, providing rationale for fibrinolytic therapy in situations where prompt PCI is not readily available or the risk of invasive intervention is considered to be prohibitive. In patients >75 years of age, fibrin-selective agents, such as recombinant tPA (tissue-type plasminogen activator)‚ appear to be more effective in reperfusing the occluded artery but with the tradeoff of increased risk for intracranial hemorrhage.144 In the context of cardiogenic shock and cardiac arrest, age is an independent predictor of death after PCI.145,146 In addition, the value of mechanical circulatory support in these cases, for example, with intra-aortic balloon counterpulsation or an Impella left ventricular assist device, is uncertain. Therefore, careful selection of patients most likely to benefit from PCI is required. In the CULPRIT-SHOCK trial (Culprit Lesion Only PCI Versus Multivessel Percutaneous Coronary Intervention in Cardiogenic Shock), in which the mean age of the study population was 70 years and 31% were >75 years of age, no age × treatment interaction was observed with regard to the benefit in favor of culprit vessel PCI only, compared with multivessel PCI during the index procedure.147
Adverse Outcomes of PCI in Older Adults: Management to Minimize Risks
Although an invasive approach appears to reduce reinfarction and the need for further revascularization, a meta-analysis shows increased bleeding among patients undergoing invasive management (OR, 2.19 [95% CI, 1.12–4.28]; P=0.02; I2=0%) compared with those treated conservatively.139 In contemporary practice, bleeding risk is reduced by the use of radial access, even among patients presenting with cardiogenic shock.148,149 Bleeding risk is further reduced with the use of the latest generation drug-eluting stents and shorter duration of DAPT.150,151 The SENIOR trial showed that in older adults with high bleeding risk, patients treated with drug-eluting stents and short-duration DAPT had a lower incidence of the composite end point of all-cause death‚ MI, stroke, or urgent revascularization compared with patients treated with bare-metal stents and short-duration DAPT with no difference in risk of bleeding.151 Additional approaches to reducing bleeding include age, weight, and kidney function adjusted dosing of antithrombotic agents, shortening the duration of DAPT, and using double rather than triple antithrombotic therapy in patients who require anticoagulation.
As the population ages, the significant advancements in interventional strategies and technologies are often applied as rationale to prioritize this option of care for the increasing number of older adults with ACS. Nonetheless, robust randomized clinical trial evidence in older patients with ACS is lacking, and geriatric domains (eg, frailty, multimorbidity, polypharmacy, cognitive function, and health care goals), which often affect outcomes, have not been incorporated into most studies. The multidisciplinary heart team, integrating geriatrics experts with cardiologists and surgeons, provides an important opportunity to enhance decision-making and clinical process.
Considerations for Clinical Practice
1.
Until a more specific risk score for older adults with ACS becomes available, the American College of Cardiology/AHA chest pain and revascularization guidelines recommend risk stratification for patients with suspected NSTEMI using the TIMI and GRACE risk scores, with added emphasis placed on high-sensitivity troponins. Geriatric syndromes are acknowledged as relevant, but they are not formally integrated into risk assessment.
2.
Immediate myocardial reperfusion by primary PCI is beneficial in older patients with STEMI, and it may also reduce recurrent MI and repeat revascularization in patients with NSTEMI, but, for patients with cardiogenic shock and cardiac arrest, careful selection of older patients undergoing PCI is warranted given their high inherent risk for adverse outcomes and futility.
3.
Strategies to mitigate the risk of major bleeding include the use of radial access; age, weight, and kidney function adjusted dosing of anticoagulant and antithrombotic therapy, and shorter duration of DAPT with clopidogrel, particularly among older adults at high bleeding risk.
4.
Ideally, the multidisciplinary team that cares for older patients with ACS includes cardiologists, surgeons, geriatricians, primary care clinicians, nutritionist, cardiac rehabilitation professionals, social workers, nurses, family members, and pharmacists, but centers should tailor their team according to available resources and patient needs.
5.
Among older patients, advanced do-not-resuscitate directives, careful discussion with the patients, family, or their power of attorney must occur before invasive management and utilization of primary PCI. If the patient undergoes invasive treatment or primary PCI, the advanced do-not-resuscitate directive should be suspended for the duration of the invasive procedure.
Surgical Revascularization in Older Adults
Surgical Risk Evaluation and Patient Selection
At present, the predicted risk of operative death is <0.5% for a man 82 years of age with no major comorbidities undergoing coronary bypass surgery and defined as death within 30 days of surgery or during the index admission.152,153 During the past 2 decades, risk-adjusted operative death associated with surgical revascularization in older patients has steadily decreased, which has been attributed to incremental improvements in case selection and perioperative management.154–156 During this time, the number of older patients undergoing surgical revascularization annually in the United States hardly changed, whereas the prevalence of risk factors and comorbidities, including diabetes, preoperative dialysis, chronic obstructive airways disease, heart failure, cerebrovascular disease and previous stroke, previous percutaneous intervention, left main stem disease, and urgent presentation, have all significantly increased.154,155
Like other risk stratification systems, most surgical risk scores do not include a formal assessment of frailty or other geriatric domains that are important determinants of outcomes after cardiac surgery in older patients.156 Frailty stands out as a particularly relevant risk. Both clinical and administrative data–based approaches to defining frailty may increase the accuracy of standard risk-prediction systems in older patients. For example, in an analysis of >2 million patients undergoing CABG between 2005 and 2016 identified using a national administrative claims database, 4.0% were considered frail according to the Johns Hopkins Adjusted Clinical Groups frailty indicator, a binary frailty variable derived from a diagnostic code cluster.157 In this analysis, frailty (ie, the presence of any one of those diagnoses) was an independent predictor of major complications and costs and associated with a >2-fold increase in the odds of operative death (adjusted OR, 2.49 [95% CI, 2.3–2.7]). The same frailty indicator has also been reported to be associated with significantly reduced long-term survival after CABG: in an analysis of 40 083 patients operated on between 2008 and 2015 in Ontario, Canada, in which 22% were defined as frail, adjusted death at 4 years was significantly higher in frail patients (adjusted hazard ratio, 1.2 [95% CI, 1.12–1.28]).158 Gait speed has also been reported to predict long-term survival after cardiac surgery.159
Efficacy of Surgical Revascularization in Older Patients With ACS
Medical literature has indicated that surgical revascularization is associated with an event-free survival benefit compared with PCI in select cohorts of older patients with left main or complex disease. Three overlapping meta-analyses of pivotal randomized trials of percutaneous versus surgical revascularization of multivessel and left main disease have evaluated mid-term outcomes in older patients, reporting that coronary bypass was associated with superior freedom from MACE compared with drug-eluting stents.160–162 In the EXCEL trial (Evaluation of XIENCE versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization), patients >75 years of age had an all-cause death of 16.6% in the PCI arm versus 8.4% in the CABG arm (OR, 1.96 [95% CI, 1.00–3.83]), and meta-regression analysis showed increasing death with advanced age with PCI.161 It should be noted that ≈60% of the EXCEL trial cohort had either stable angina or silent ischemia, whereas those who presented with recent ACS events (within 7 days of randomization) are ≈40% of the cohort. Thus, the generalizability of the results to all older patients with ACS is limited. However, caution should be exercised when interpreting data from the EXCEL trial because the study population mostly consisted of patients with stable angina rather than those with ACS and complex geriatric syndromes (stable angina, ≈53%; recent MI within 7 days of randomization, ≈15%; unstable angina with negative biomarkers, ≈24%). The event-free survival benefit observed in patients who received coronary bypass was primarily driven by lower risk of repeat revascularization and MI.160–162 Lesion complexity appears to be highly relevant: in a meta-analysis of 4686 patients with unprotected left main stem disease randomly assigned in 6 trials, PCI was associated with lower death than coronary bypass in patients with SYNTAX score ≤22, but higher death in patients with SYNTAX scores ≥33.160 In these meta-analyses, the risk of early stroke was higher in surgical patients; however, a recent analysis of 1680 patients who underwent either PCI or CABG while participating in a prospective study of 23 860 adults undergoing 2 memory tests per year as part of a national longitudinal study on aging showed no significant differences between PCI and CABG in memory score or dementia up to 10 years after revascularization.163
Adverse Events of Surgical Revascularization in Older Adults: Management to Minimize Risk
Less invasive surgical approaches such as off-pump and hybrid revascularization are aimed at reducing postoperative morbidity, particularly in older patients. However, the GOBCABE trial (German Off-Pump Coronary Artery Bypass Grafting in Elderly Patients), in which 2539 patients >75 years of age were randomly assigned to on-pump or off-pump surgery, suggests that off-pump techniques have no effect on stroke or new dialysis, and the most important surgical determinant of event-free survival after coronary bypass surgery in older patients is completeness of revascularization.164,165 In this landmark trial, the rate of death at 5 years was similar in patients who underwent off-pump (361, 31%) versus on-pump (352, 30%) surgery, as was the composite outcome of death, MI, and repeat revascularization (33% versus 34%, respectively).164 Incomplete revascularization, which was more common in off-pump than in on-pump coronary bypass surgery, was associated with significantly worse survival at 5 years (hazard ratio, 1.2 [95% CI, 1.01–1.39]). In this trial, there was no significant difference at 30 days in the incidence of stroke between on-pump and off-pump surgery, or between the incidence of stroke in patients undergoing off-pump surgery stratified according to aortic clamping versus no-touch techniques.165 Stroke rates may be minimized by individualized operative techniques and perioperative management, including aggressive prevention and treatment of atrial fibrillation and tailored pre- and intraoperative imaging of aortic and cerebrovascular disease.166 Postoperative delirium remains an important adverse outcome during index MI hospitalization, and proactive efforts to identify and prevent delirium postoperatively are warranted.71 Rate of memory decline has been reported to be worse after off-pump than after on-pump coronary bypass surgery, which may predominantly reflect patient selection but serves as a caution against pursuing less-invasive surgical revascularization strategies such as hybrid procedures in older patients with multivessel disease who may derive greatest long-term benefit from complete and durable revascularization.163
Prevention of Aki in Older Patients Undergoing Revascularization
More than half a million percutaneous or surgical revascularization procedures are performed annually in the United States.167 Older patients are more likely to develop adverse outcomes such as contrast-induced AKI than younger patients because of underlying comorbid conditions such as CKD, diabetes, hypertension, and volume depletion. Contrast-induced AKI is defined as ≥0.5 mg/dL or 25% increase of serum creatinine from the baseline value at 48 hours after contrast media administration.168 The risk of AKI among patients undergoing revascularization varies with the volume of contrast and the patient’s baseline risk.169
Several measures can be implemented to prevent contrast-induced AKI after coronary interventions. Radial artery PCI is a potential method for decreasing AKI by prevention of bleeding or by reduction and avoidance of direct embolization into the renal circulation. The AKI-MATRIX trial (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of angioX) show that radial artery PCI compared with femoral artery PCI resulted in a 13% reduction in AKI (adjusted hazard ratio, 0.87 [95% CI, 0.77–0.98]), defined as either an absolute (0.5 mg/dL) or relative (>25%) increase in serum creatinine from baseline. In subgroup analyses, radial compared with femoral access was associated with 20% less AKI in patients ≥75 years of age. Overall, age >75 years (OR, 1.99 [1.75-2.27]), diabetes (OR, 1.33 [1.16–1.52]), anemia (OR, 1.20 [1.04–1.39]), and contrast media volume per 100 mL (OR, 1.34 [1.26–1.72]) were independent risk factors for AKI.170 Evaluation of data from the National Cardiovascular Data Registry showed that a patient-centered approach to contrast use can attenuate the risk of AKI.171 Using the formula 3 × estimated glomerular filtration rate to define contrast volume threshold, the authors found an AKI rate of 14.5% when the contrast volume threshold was exceeded versus 9.8% if the volume was below the threshold. Meaningful reductions in contrast-induced AKI risk can be attained by decreasing contrast volume among patients undergoing PCI. Best kidney practices for older adults with ACS are summarized in Table 4.172–174
| Best kidney practices |
|---|
| Preprocedure identification of older patients at risk for CI-AKI with the aim to stabilize renal function before coronary intervention in the context of acute coronary syndrome. Risk factors include preexisting kidney disease, diabetes, hemodynamic instability, and those on nephrotoxic medications. |
| If patients are not at risk for acute pulmonary edema associated with reduced left ventricular function, assess volume status and consider gentle preprocedure volume resuscitation, holding of diuretics to protect against CI-AKI, or both. |
| Avoid hyperosmolar CM and minimize dose of isoosmolar or low-osmolar CM to avoid CI-AKI. A recommended dose of CM to avoid AKI: 3 × estimated glomerular filtration rate. |
| The use of transradial PCI to lower risk of AKI, bleeding, and death is important and avoidance of renal toxins, nonsteroidal anti-inflammatory drugs, diuretics, and aminoglycosides; adjustment of medication doses for reduced estimated glomerular filtration rate; and reduction of polypharmacy in the older patients are critical. |
| Avoid hypotensive episodes to protect renal function, particularly among patients with left ventricular impairment. |
| Rule out other causes of AKI before procedures (obstruction, volume depletion, sepsis). |
| In case of multivessel PCIs, procedures can be staged to allow renal recovery. |
| Among patients already on dialysis, coordination of PCI procedures and dialysis with the renal team. |
| Short duration (1–3 mo) of dual antiplatelet therapy with drug-eluting stent in patients with chronic kidney disease reduces bleeding events after PCI. |
AKI indicates acute kidney injury; CI-AKI, contrast-induced acute kidney injury; CM, contrast media; and PCI, percutaneous coronary intervention.
Considerations for Clinical Practice
1.
Among selected older adults with left main or multivessel coronary disease, CABG has been associated with improved survival and lower risk of repeat revascularization and MI compared with PCI, but for older patients, a Heart Team approach to revascularization strategy is suggested, including geriatrics expertise to assess frailty, multimorbidity, cognition, and other pertinent age-related elements of care.
2.
Society of Thoracic Surgeons Patient-Reported Outcome Measures score quantifies the risk of early death after CABG at all ages; however, important additional considerations that may reduce the feasibility of safe and effective surgical revascularization or affect the goals of care are commonly encountered in older patients, including severe cognitive impairment, frailty, cerebrovascular disease, and aortic calcification.
3.
Among older adults with left main or multivessel coronary disease, CABG surgery with the goal of complete revascularization has shown survival benefits, but shared decision-making with patient and family is critical, particularly among very old adults. The use of percutaneous revascularization with medical therapy or medical therapy alone are also reasonable options if symptom control is a primary patient-centered goal.
4.
Stroke risk can be minimized by tailoring operative techniques and perioperative management to include pre- and intraoperative imaging of aortic and cerebrovascular disease, and aggressive prevention and treatment of atrial fibrillation.
FutiLity
Futility has been defined as (1) “as a lack of medical efficacy, particularly when the therapy is unlikely to produce its intended clinical result, as judged by the physician; or lack of a meaningful survival, as judged by the personal values of the patient”175; (2) “advanced life-prolonging treatments that would almost certainly result in a quality of life that the patient has previously stated that he/she would not want”; or (3) “when there is no reasonable expectation that the patient will improve sufficiently to survive outside the acute care setting.”176 It is frequently challenging to predict or recognize futility or gain consensus from the patient and caregivers, particularly after percutaneous or surgical revascularization when concerns around publicly reported outcomes may influence the decision to pursue aggressive care in the end-of-life setting. Establishing goals of care in older patients from the outset may help avoid unwanted or futile intervention.6 Mechanical circulatory support for surgical revascularization, in general, is futile in older patients with advanced geriatric syndromes (such as delirium and cognitive impairment, frailty, multimorbidity, and polypharmacy), very poor baseline functional status, or prohibitive surgical risk (defined as Society of Thoracic Surgeons Patient-Reported Outcome Measures >20%).
The confirmation of futility often remains ambiguous and even misinterpreted within contemporary management. Those who are not candidates for procedures because of perceived futility often benefit significantly from palliative care, such that the concept of futility does not imply withdrawal of care.
Key Points
1.
Futility is a lack of medical efficacy when the therapy is unlikely to produce its intended clinical result or meaningful survival as judged by the Heart Team.
2.
Determining a priori goals of care in older patients may help avoid unwanted or futile intervention.
3.
For older patients at a high risk for death and adverse outcomes, a major challenge is to identify futility before rather than after revascularization, but establishing goals of care in older patients from the outset may help avoid unwanted or futile intervention.
Transitions, Cardiac Rehabilitation, and Follow-up
Transitions of Care in Older Adults
ACS is associated with significant morbidity and death, and older adults are at highest risk.177 The 30-day readmission rate after ACS ranged from 11% to 14% in a meta-analysis of 14 studies.178 Death rates vary among populations and range from 7% to 18% in the first year after STEMI.106 These adverse outcomes suggest that transitions in care from hospital to home and to primary care are important and are a target for improvement. Continuity in care is particularly critical for aging adults who are more likely to experience frailty, multimorbidity, depression, cognitive decline, diminished functional status, and a higher symptom burden.180 For example, depression is 3 times more common in patients after MI and complicates adherence to guideline-directed therapies, self-care, and clinic visits.180 In addition, coronary disease predominantly affects older adults, so multimorbidity is expected and contributes to MACE after ACS, making coordinated care critical during transitions.
On the basis of a Get With The Guidelines approach, Goldman and Harte177 recommended that the post-ACS discharge plan address 6 elements, including (1) medications, (2) lifestyle modification/cardiac rehabilitation, (3) management of comorbidities, (4) psychosocial support, (5) socioeconomic factors, and (6) patient/family education to include teaching and preparation of patients for their own self-care (Figure 4). Polypharmacy is a frequent issue for older adults and transitions in care should include consideration of deprescribing potentially inappropriate medications and medications that are no longer needed.28 To achieve optimal care coordination, the multidisciplinary team benefits from inclusion of the cardiologist and surgeon (when relevant), and the primary care clinician, geriatrician, nurses, social worker, patient, and the patient’s family or significant other(s), as well, with ready access to pharmacists, dieticians, psychologists, occupational therapists, and case managers as needed. The older adult’s general health status is often a key patient-centered outcome that must be considered in addition to improving survival.180 The AHA highlights prioritizing 3 components of the patient’s health status, including symptom burden, functional status, and quality of life.182–184 Monitoring these domains during postdischarge follow-up can provide insight into how the patient is progressing relative to their goals of care and where there is potential for improvement.
The complexity of care required for many older adults after hospital discharge can lead to gaps in care, and multidisciplinary coordination is essential to ensure that all aspects of care are integrated into a cohesive plan. High-quality transitional care and case management can reduce the risk of recurring adverse events and improve patient-centered outcomes such as functional status and symptom control.
Key Points
1.
Transitions of care are high-risk times for older adults after ACS; coordination of surgeons (when relevant), cardiologists, geriatricians, nurses, pharmacists, and primary care clinician is integral to successful discharge/transitional care plan for older patients with ACS. Goals to better harmonize diverse clinicians involved with the care of older patients with ACS remains a challenging goal of care.
2.
A detailed medication review and reconciliation is essential, ideally in collaboration with a pharmacist, to ensure that, once at home, the patient has access to and is taking the medications prescribed at discharge and that they are integrated with any additional pharmaceuticals acquired over-the-counter and from other clinicians.
Palliative and End-of-Life Care in Older Adults
ACS is a sentinel event that can lead to deterioration in cognitive function, increasing frailty, loss of overall function, independence, and self-confidence among older patients. This presents a challenge to patients, their caregivers, and clinicians providing primary and specialty care, particularly when evaluating decision-making. Palliative care is an important step in providing optimal treatment and support to patients and caregivers. The World Health Organization estimates that those with CVD have the greatest need for palliative care. Warraich et al185 note that aggressive symptom management should be the cornerstone of management of CVD at the end of life rather than persistent life-prolonging therapies.
Palliative care is defined as an interdisciplinary approach to improving quality of life and reducing suffering among patients with serious illness. Core domains include: (1) treating physical symptoms, (2) psychosocial care, (3) identifying the patient’s priorities for care, and (4) patient and caregiver support for decision-making. The National Coalition for Hospice and Palliative Care published the Clinical Practice Guidelines for Quality Palliative Care185a and included 8 domains: (1) structure and processes of care, (2) physical aspects of care, (3) psychological and psychiatric aspects of care, (4) social aspects of care, (5) spiritual, religious, and existential aspects of care, (6) cultural aspects of care, (7) care of the patient nearing the end of life, and (8) ethical and legal aspects of care. It is especially important to assess patient-reported symptoms and quality of life because symptoms and well-being do not necessarily correlate with objective measures of disease severity. Palliative care differs from hospice care in that hospice requires an estimated life expectancy of ≤6 months. Furthermore, palliative care does not preclude hospitalization or life-prolonging interventions, whereas hospice care generally promotes comfort measures only.
Although there are few studies that focused on ACS alone, for patients with ACS complicated by severe heart failure, home and team-based palliative interventions improved patient-centered outcomes, health-related quality of life, documentation of preferences, and health care utilization. The burden of CVD is increasing, and evidence in support of various palliative care delivery methods is growing. This provides an opportunity to adopt and integrate palliative care measures into the standards of cardiovascular care. Aggressive management of patients’ symptoms is critical to improving their quality of life. Rigorous studies are needed to better define optimal timing, utilization, and implementation of palliative care into practice for older patients with ACS.
Key Points
1.
End-of-life management should be made available to all patients with progressive CVD to treat symptoms and improve quality of life.
2.
Research is needed to better determine the utility and timing of palliative care interventions in older patients with ACS and how to best integrate palliative care precepts into standard post-ACS care.
3.
Patient-reported outcome measures should encompass measure of function and health-related quality of life, symptoms and symptom burden, and health behavior.
CR in Older Adults
CR is a comprehensive secondary-prevention CVD management program that uses exercise training, behavioral modification, education, and psychosocial counseling to improve outcomes in patients with ACS and other conditions. CR has been demonstrated to reduce recurrent CVD events, death, and rehospitalizations, and improve cardiorespiratory fitness, physical function, self-efficacy, and quality of life, as well. CR is an important component of ACS care for older adults, with benefits applying across the clinical spectrum from those who are vigorous, robust, and confident to those who are weak, sedentary, and fearful.186 CR has particular value for older adults because it provides an opportunity to develop personalized approaches to cardiovascular health in the context each patient’s aggregate health care challenges.186
Key components of CR include an initial medical assessment to determine a patient’s CVD status, and the comorbidities that may affect symptoms, signs, and cumulative medication effects, as well.187 Carefully prescribed exercise training regimens are also fundamental, with the goal to assess baseline capacity and to design tailored approaches that improve physical function over time.183,184 Medical assessments provide opportunity for medication review and reconciliation, and referral to clinicians who can address relevant medical issues (CVD and non-CVD).183,184 Risk reduction and psychosocial support can also be implemented, and steps to align overall care with each patient’s personal goals of care. Most CR programs incorporate significant care partners (spouses, partners, adult children) to reinforce learning and support structures for the patient, and also to advance the premise of healthfulness that benefits the whole family.183,184
Despite age-related benefits of CR, participation declines with increasing patient age, and only 25% of older patients eligible for CR actually participate.188 Women also tend to participate less often than men across all ages, but because women outlive men, these gaps tend to worsen among older adults.189 Common barriers include a lack of understanding among patients and clinicians of the value of CR, prohibitive logistics particularly because many older adults cannot drive, unaffordable copayments for CR for patients on fixed incomes, and inflexibility in format to achieve personalized therapeutic approaches in CR that are tailored to the wide range of needs and circumstances among older adults. Although many contemporary initiatives now aim to improve CR participation using remote-based formats, often incorporating smartphones and wearable devices to facilitate and inform this care, the usability and safety of these novel methods for older adults who are frail, cognitively limited, and medically complex is still largely uncertain.
Benefits of CR in Older ACS Patients
CR Addresses Heterogeneity of Older Adults
Principles of ACS disease management are potentially transformed by each patient’s health circumstances. An older adult who is relatively robust is likely to have benefitted from revascularization and well-tolerated adjunctive therapies. Such a patient derives valuable benefit from CR through exercise and activity regimens that aim to increase cardiorespiratory fitness in combination with guidance to mitigate risks of overexertion and injury. Likewise, CR provides a robust patient, that is, those without physical frailty or prefrailty, the opportunities to better understand ACS pathophysiology and treatment precepts, insights that correlate to improved adherence and diminished anxiety. Robust patients also benefit from improved understanding of symptoms, sleep hygiene, diet, and other aspects of care.
CR also benefits patients who are frail and sedentary. In this case, CR fosters safe and effective exercise strategies that promote physical function and confidence. Initial emphasis on strength and balance training in CR is often essential to provide a foundation before aerobic training is feasible. The effects of comorbidity, medications, nutrition, sleep, cognition, and fear are also factored into therapeutic goals and strategies. Patients who are the most functionally impaired often benefit the most from CR in terms of their relative improvements in function and quality of life.190
CR Targets Improved Functional Capacity
Whereas CVD research is typically predicated primarily on end points of MACE, CR benefits include enhanced physical function.191 For many older adults, this is their primary goal of care, because it is associated with self-efficacy, independence, and improved quality of life. CR fosters opportunity for patients to maintain or regain vigor despite disease by targeting progressive strength, endurance, and cardiorespiratory fitness, with the associated aims of increased daily activity and long-term health.192
Although a definitive therapy for frailty is still not known, exercise training and nutrition show promise.193,194 CR provides critical supervision for patients who are easily fatigued and highly susceptible to falls and injury. Multiple studies demonstrate the utility of CR to restore physical function and improve outcomes.190,195 Although a cardiac hospitalization has the potential to trigger a cascade of progressive weakening and disablements for older adults who are frail, CR can potentially restore sufficient function for independence to be preserved. The concept of prehabilitation extends from CR as a complementary strategy to mitigate frailty risks even before surgical revascularization is undertaken.196
Whereas older patients with severe frailty are often excluded from cardiac surgery, patients who are treated with PCI or medical management may be relatively more functionally impaired. Ironically, the rate of referral of surgical patients to CR exceeds that for PCI and medical management, with the implication that many older patients undergoing PCI and medically managed ACS do not get the much-needed benefits of CR.197 A secondary goal of a CR program is to identify older patients at a low socioeconomic status, with a lack of social support, and at a high risk for chronic stress, anxiety, and depression. The CR program can thus provide tailored interventions to enhance psychosocial support and care for older patients after ACS admission.197
Considerations for Clinical Practice
1.
CR targets functional enhancement as a key outcome benefit. For many older adults, this is a vital clinical priority that is not fostered by other aspects of treatment, thereby reinforcing the distinctive value of CR.
2.
CR is best used with a tailored approach that addresses each patient’s distinctive circumstances and goals of care.
3.
Frailty is biologically linked to CAD and plays a key role in ACS management. CR provides opportunity for strength training, nutritional emphasis, and other strategies to mitigate frailty effects and improve patient-centered outcomes. Whereas many clinicians avoid CR for patients who are frail, in fact, patients who are frail often benefit the most.
Conclusion
The management of ACS in the older adult population is more complex than in younger patients because of their anatomic complexity, physiological vulnerability, age-related risks (including prevalent geriatric syndromes), and heterogeneity in life expectancy and goals of care. In this scientific statement, we propose a framework to integrate geriatric risks into the management of ACS, including the diagnostic approach, pharmacotherapy, revascularization strategies, prevention of adverse events, and transition care planning. Post-MI care should include CR tailored to address each patient’s aggregate circumstances and personal goals of care.
| Writing group member | Employment | Research grant | Other research support | Speakers’ bureau/honoraria | Expert witness | Ownership interest | Consultant/advisory board | Other |
|---|---|---|---|---|---|---|---|---|
| Abdulla A. Damluji | Johns Hopkins University Inova Center of Outcomes Research | None | None | None | None | None | None | None |
| Daniel E. Forman | University of Pittsburgh Medical Center | None | None | None | None | None | None | None |
| Karen P. Alexander | Duke Clinical Research Institute, Duke University | None | None | None | None | None | None | None |
| Joanna Chikwe | Heart Institute, Cedars Sinai Medical Center | None | None | None | None | None | None | None |
| Holli A. DeVon | University of California Los Angeles School of Nursing | None | None | None | None | None | None | None |
| Vijay Kunadian | Newcastle University Translational and Clinical Research Institute (United Kingdom) | None | None | None | None | None | None | None |
| Robert L. Page II | University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences | None | None | None | None | None | None | None |
| Michael W. Rich | Washington University School of Medicine | NIH (co-investigator)† | None | None | None | None | None | None |
| Tracy Y. Wang | Duke Clinical Research Institute | Abbott*; AstraZeneca†; BMS*; Boston Scientific*; Chiesi*; Cryolife† (all research grant to Duke University) | None | None | None | None | AstraZeneca*; CSL Behring*; Cryolife*; Novartis* | None |
| Bessie A. Young | University of Washington | Chou Foundation (research grant)*; Kuni Foundation (co-investigator)* | 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 or more during any 12-month period, or 5% or more of the person’s gross income; or (b) the person owns 5% or more of the voting stock or share of the entity, or owns $5000 or more 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 | Employment | Research grant | Other research support | Speakers’ bureau/honoraria | Expert witness | Ownership interest | Consultant/advisory board | Other |
|---|---|---|---|---|---|---|---|---|
| Mazen S. Abu-Fadel | Oklahoma Heart Hospital, North Campus | None | None | None | None | None | None | None |
| Héctor Bueno | Centro Nacional de Investigaciones Cardiovasculares (Spain) | AstraZeneca†; Novartis*; PhaseBio*; Organon*; Instituto de Salud Carlos III, Spain (competitive public research grants)†; Sociedad Española de Cardiologia (competitive research grants)† | None | AstraZeneca†; Novartis*; Organon* | None | None | AstraZeneca†; Novartis*; Organon* | None |
| Leslie L. Davis | University of North Carolina at Chapel Hill | UNC Chapel Hill (Intramural grant)† | None | None | None | None | None | None |
| Mark B. Effron | Ochsner Medical Center | None | None | None | None | Eli Lilly and Company† | None | Eli Lilly and Company (pension)† |
| Shamir Mehta | McMaster University (Canada) | AstraZeneca (Complete trial)†; Boston Scientific (Complete Trial)† | None | None | None | None | None | None |
| Stefano Savonitto | Manzoni Hospital (Italy) | None | None | None | None | None | None | None |
This table represents the relationships of reviewers that may be perceived as actual or reasonably perceived conflicts of interest as reported on the Disclosure Questionnaire, which all reviewers are required to complete and submit. A relationship is considered to be “significant” if (a) the person receives $5000 or more during any 12-month period, or 5% or more of the person’s gross income; or (b) the person owns 5% or more of the voting stock or share of the entity, or owns $5000 or more 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.
Acknowledgment
The authors would like to acknowledge Dr Paul St. Laurent, Senior Science and Medicine Advisor (Lead), for his assistance and administrative role with this AHA scientific statement.
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