Introduction
The demographic trends of the overall population, particularly in the United States, reveal a progressively aging population with significantly longer mean life expectancy than in prior decades. Since aging is itself a major risk factor for the development of atherosclerosis, a consequent steady rise in the incidence and prevalence of this ischemic heart disease (IHD) has been demonstrated over the last 30 years. Elderly patients, especially those older than 75 years, are relatively underrepresented in many of the key clinical trials that substantiate major society guidelines for evaluation and management of IHD [1]. Moreover, elderly patients have significantly more comorbidities and increased medical and procedural risk of adverse events related to what are otherwise considered guideline-directed treatments. In this article I provide an evidence-based approach to the evaluation and management of IHD in elderly patients that focuses on improved cardiac outcomes, quality of life, and safety.
Defining Elderly
There is no single cutoff value for chronological age that defines an elderly patient. Many people would approximate the range of 70–75 years as elderly. For the purposes of this article, we will define older as being aged 75 years or older unless otherwise specified. However, it is important to note the distinction between chronological age and frailty, the latter of which accounts more directly for many of the risks associated with aging, and may develop much earlier or later than the eighth decade of life. It is expected that by 2030, approximately one-fifth of the world population will be older than 65 years. By 2050, the subgroup of persons older than 85 years is expected to triple. The average medical complexity of the cardiac patient will undoubtedly increase over this period and stand to benefit even more from individualized decision-making.
Aging as a Risk Factor
Older age emerges as a risk factor for IHD in several different populations, subgroups, and clinical settings. The Framingham Heart Study database shows an age-related increase in the incidence of coronary heart disease among men and women [2]. In the United States, more than 80% of cardiovascular deaths and more than 85% of hospitalizations occur in persons older than 65 years [1]. The aging process is itself tied to the pathogenesis of atherosclerosis. The cumulative effects of oxidative stress and inflammation that occur with aging directly contribute to vascular stiffening of the central vasculature and microvascular disease, particularly as intrinsic homeostatic mechanisms, such as telomere shortening, diminish [3]. Additionally, the proinflammatory effects of long-standing traditional cardiovascular risk factors and other comorbid conditions increase susceptibility to cardiovascular disease [4].
Elderly Patient with Cardiovascular Disease Is a Higher-Risk Subgroup
There are a number of reasons why older age predisposes to high cardiovascular morbidity and mortality. Both the number and complexity of atherosclerotic lesions on angiography tend to be higher. Additionally, delays in initiating therapy for acute coronary syndromes frequently occur [1, 5]. In the setting of sudden thrombotic coronary occlusion, the benefit of emergent coronary revascularization diminishes in direct proportion to the time to reperfusion. Elderly patients, especially diabetic patients, are more likely to experience symptoms atypical of myocardial ischemia during an acute coronary syndrome (e.g., nausea, diaphoresis, or epigastric pain as opposed to chest pain or pressure). As a result, they frequently present later in the event, and may be misdiagnosed by health care providers because of the absence of chest discomfort [6, 7].
It is important to note that clinical trials often exclude older adults with multiple complex health-related concerns, such as multimorbidity, polypharmacy, limited access to care, financial stress, and iatrogenesis related to age. Consequently, the therapeutic benefits of certain medical or procedural treatment modalities demonstrated in certain trials cannot be clearly extrapolated to older patients because of the presence of some these factors [8]. Many cardiovascular interventions that are effective in patients under the age of 65 are more likely to adversely affect older adults, especially if they are frail. Drug-eluting stents necessitate dual antiplatelet drug therapy to minimize the risk of acute stent thrombosis; however, these agents significantly increase bleeding risk in older patients [9]. Beta-blockers, commonly prescribed because of the associated survival benefit following acute myocardial infarctions (MIs), can limit chronotropy and exercise performance [8]. Nitrates are very commonly used antianginal agents that may cause excessive vasodilation leading to syncope or falls [5, 10]. Management recommendations in current treatment guidelines place primary emphasis on mortality. In elderly patients with cardiovascular disease, there are additional end points to consider, such as quality of life, independence, cognition, physical function, pain, and costs.
Managing Ischemic Heart Disease in Elderly Patients
Medical Therapy
All patients with stable IHD (SIHD) should be initially treated with optimal medical therapy. Aspirin therapy is effective for primary and secondary prevention of cardiovascular events in adults, including elderly patients. The Antiplatelet Trialists’ Collaboration conducted a systematic overview of 145 randomized trials that evaluated vascular events (nonfatal MI, nonfatal stroke, or vascular death) among patients receiving prolonged antiplatelet therapy versus controls. Aspirin therapy was found to significantly avert a greater number of vascular events per 1000 patients compared with controls, regardless of the age group [11]. The benefits of thienopyridine agents, however, are less clear in SIHD. There is a strong rationale for use of clopidogrel, prasugrel, and ticagrelor for treatment of acute coronary syndrome combined with aspirin, but bleeding risks are also increased. In TRITON-TIMI 38, prasugrel was associated with greater harm than benefit in adults aged 75 years or older [12]. Elderly patients are more likely to receive excess doses of antithrombotic agents, including unfractionated heparin, low molecular weight heparin, and glycoprotein IIb/IIIa inhibitors. Predictors of excess dosing include older age, renal insufficiency, female sex, and low body weight [13]. Therefore lower dosing and omission of loading doses are important considerations to help mitigate the risk of bleeding and harm.
Beta-blocker therapy confers increased survival in elderly persons with SIHD following an MI. Rochon et al. [14] evaluated the relation between the use of beta-blockers and hospital admission for heart failure and 1-year survival in a cohort of all older patients surviving MI in Ontario, Canada. They collected data on a cohort of 13,623 patients aged 66 years or older and who were discharged from a hospital after an MI, comparing outcomes in those who did not receive beta-blockers with outcomes of those who received low, standard, or high doses of beta-blockers. The 1-year adjusted risk ratio for death in the beta-blocker arms was significantly lower than that in the arm with no beta-blocker, and this benefit persisted even in the healthiest group. This benefit must always be counterbalanced by the potential risks of exercise intolerance, chronotropic incompetence, and depression that may occur secondary to beta-blocker use.
The use of ACE-inhibitors in elderly patients with SIHD was evaluated in the HOPE trial, which enrolled 9297 patients with stable vascular disease or diabetes and randomized them to receive ramipril or placebo [15]. Outcome data were stratified on the basis of age younger than 70 years and 70 years or older. Ramipril significantly reduced the primary end point and each of its components (cardiovascular death, MI, and stroke) in patients aged 70 years or older compared with placebo.
The benefits of statin therapy in elderly patients with coronary heart disease is very well demonstrated in clinical trials. The overall impact of statins on all-cause mortality in elderly patients was illustrated by a meta-analysis by Afilalo et al. [16]. Their meta-analysis included nine trials involving 19,569 patients aged 65–82 years with documented coronary heart disease who were randomized to receive either statin therapy or placebo. Over 5 years, statin therapy was associated with a 22% reduction in all-cause mortality. In addition, statins also reduced coronary heart disease mortality by 30%, rate of nonfatal MI by 26%, the need for revascularization by 30%, and rate of stroke by 25%. The 2013 National Cholesterol Education Program guidelines now recommend lower statin dosing for patients aged 75 years or older. While such an age-stratified recommendation may reduce the risk-benefit ratio, it is not based on specific data. There may be subsets of elderly patients who still benefit from high-dose statin therapy [17].
Coronary Revascularization
Coronary revascularization with either percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) can be offered to elderly patients with IHD; however, the risks must be carefully considered. Data from the National Cardiovascular Network were used to evaluate in-hospital morbidity and mortality among patients (stratified by age: younger than 80 and 80 years or older) undergoing PCI or CABG at 22 centers (1994–1997). The risks to octogenarians undergoing PCI were twofold to fourfold higher than those to younger patients, strongly influenced by comorbidities. Octogenarians undergoing CABG had fewer comorbid illnesses but higher disease severity and surgical urgency than younger patients. For both PCI and CABG, in-hospital mortality increased with increasing age [18, 19].
Revascularization techniques are progressively improving, which helps create lower risk-benefit ratios in PCI-based revascularization strategies, including in elderly patients. Temporal PCI trends show a greater proportion of PCIs being accomplished in older and more complex patients over time [20]. There is greater success with and efficacy of drug-eluting stents as compared with bare metal stents in older adults [21]. Transradial approach PCI appears to be feasible for most elderly patients and with reduced risk of major adverse cardiovascular events compared with transfemoral access [22].
The TIME Investigators [23] evaluated invasive versus optimal medical therapy in elderly patients with symptomatic coronary artery disease. There was an increased risk of death early in follow-up in the invasive therapy group, but fewer hospital admissions for acute coronary syndrome or MI later. In the COURAGE study, PCI as an initial strategy added to optimal medical therapy did not reduce the primary composite end point of death and nonfatal MI, or reduce the rate of major cardiovascular events, as compared with optimal therapy alone during a follow-up period of 4.6 years in stable patients with a history of coronary artery disease and objective evidence of myocardial ischemia by noninvasive testing [24]. The Alberta Provincial Project for Outcomes Assessment in Coronary Heart Disease (APPROACH) is a clinical data collection and outcome monitoring initiative capturing all patients undergoing cardiac catheterization and revascularization in the province of Alberta, Canada, since 1995. Graham et al. studied survival by prescribed treatment (CABG, PCI, or medical therapy) for patients in three age categories: younger than 70 years, 70–79 years, and 80 years or older [25]. At the baseline, older patients were more likely to have cerebrovascular disease, peripheral vascular disease, hypertension, and diabetes, more likely to have more urgent indications for catheterization and severe artery disease, and less likely to undergo CABG compared with younger patients. Survival rates at 4 years significantly decreased with increasing age above 70 years. Patients aged 80 years or older had the lowest 4-year survival rate. However, any form of revascularization in this cohort yielded significantly higher 4-year survival rates compared with medical therapy.
A question that remains unanswered is whether PCI or CABG offers greater survival benefit in elderly patients who undergo revascularization. In the ASCERT study, Weintraub et al. [26] linked the American College of Cardiology Foundation National Cardiovascular Data Registry and the Society of Thoracic Surgeons Adult Cardiac Surgery Database to claims data from the Centers for Medicare and Medicaid Services for the years 2004 through 2008 to compare effectiveness of PCI and CABG in patients aged 65 years or older. The comparator arms included CABG patients (n=86,244) and PCI patients (n=103,539), with a primary end point of all-cause mortality. The median follow-up period was 2.67 years. At 1 year, there was no significant difference in adjusted mortality between the groups. At 4 years, there was lower mortality with CABG than with PCI [26]. Therefore advanced age by itself should not be an indication to choose PCI over CABG in appropriate surgical candidates whose anatomy is favorable for bypass grafting.
Cardiac Rehabilitation
Cardiac rehabilitation is a particularly valuable therapy for older IHD patients. Large Medicare registry data for patients aged 65 years or older hospitalized for coronary conditions or revascularization show cardiac rehabilitation users have 20–50% lower 5-year mortality rates. Mortality reductions extend to all demographic and clinical subgroups, including acute MI, revascularization, and congestive heart failure [27]. The benefits associated with cardiac rehabilitation include increased functional capacity with decreased myocardial work, increased skeletal muscle capacity, enhanced quality of life, reduced depression, and decreased BMI and body fat [6].
Cardiac Care in Elderly Patients: Maximizing Benefit with Minimized Risk
The key to managing elderly patients with IHD lies in patient-centered individualized decision-making. Proper delineation of the risk and benefit of any treatment option necessitates a comprehensive understanding of all cardiac and noncardiac factors present in any given patient. How closely an elderly patient clinically resembles the cohort of participants in a clinical treatment trial is crucial for understanding how well the risks and benefits of the treatment can be extrapolated to that person. Improved screening for comorbidities and geriatric syndromes may identify patients less likely to derive benefits from aggressive care.
Medication Reconciliation
Meticulous medication reconciliation during transitions of care, with emphasis on minimizing polypharmacy, as well as close monitoring for pharmacologic iatrogenesis, is crucial practice to minimize drug interactions, toxic effects, and adverse events [5].
Palliative Care
Formal conversation regarding overall goals of care determines whether certain treatment options will directly contribute to achieving those goals, regardless of their impact on other end points such as longevity. Integrating patient preferences into care plans may reveal a desire for more palliative approaches that maximize quality of life despite deviating from guideline recommendations that focus on improved survival [6].
Conclusion
Demographic trends highlight a growing number of elderly patients living longer, with more prevalent and higher-risk profiles of IHD, and increased overall medical complexity. The evaluation and management of IHD according to society guidelines are based on end points that become less applicable to elderly patients depending on their comorbidities and the goals of care. Patient-centered individualized treatment strategies that maximize benefit and minimize risk for every patient are essential to adequately meet the health care burden of IHD in the elderly population, both now and in the decades to come.