In 2050, persons aged ≥ 85 years, also known as the oldest old, are projected to reach 18 million, accounting for 4.5% of the US population, up from 2.5% in 2030.1 These patients are the fastest growing segment of the US population.
Advances in treating cardiovascular (CV) disease over the past 2 decades have led to an increased incidence of heart failure (HF) and hospitalizations among older patients.2 Total costs of care for persons with HF have exceeded $30 billion annually and are expected to rise to more than $70 billion by 2030 due to growth of the aging population.3,4 Moreover, the Framingham Study reported mortality increases with advancing age (HR 1.27 and 1.61 per decade in men and women, respectively).5
The prevalence of HF is also high and increasing over time. The National Health and Nutrition Examination Survey reported that about 5.7 million Americans have HF.6 The prevalence of HF is expected to reach 8 million by 2030.6 The higher numbers of HF among patients with advanced age is associated with age-related changes in CV structure and function, including reduced responsiveness to β-adrenergic stimulation, impaired left ventricular diastolic filling, and increased vascular stiffness. In addition, age-related changes in other systems might contribute to a HF diagnosis or worsening of the condition.7
Older adults experience physiologic changes in pharmacokinetics and pharmacodynamics, including decreased volume of distribution and creatinine clearance, which lead to significant changes in drug concentration and effectiveness.8
Geriatric patients aged > 65 years who have comorbidities and those who reside in long-term care settings are underrepresented in clinical trials, leading clinicians to make treatment decisions based on data from younger, community-dwelling individuals. Researchers have questioned whether to include elderly patients and those with comorbidities in clinical trials, given that their diminished response may produce less conclusive results with smaller treatment effects. Exclusion criteria based on comorbid conditions or functional status disqualify many older adults from clinical trials.
This article reviews evidence from major randomized controlled trials over the past 2 decades and explores their applicability to support HF treatment guidelines in patients with advanced age (Table).
Pharmacotherapy for Heart Failure
Angiotensin-Converting Enzyme Inhibitors
Several randomized clinical trials have found that angiotensin-converting enzyme (ACE) inhibitors improve symptoms in patients with HF. The CooperativeNorth Scandinavian Enalapril Survival Study (CONSENSUS), demonstrated that enalapril improves survival in patients with New York Heart Association (NYHA) class IV HF with reduced ejection fraction (HFrEF) when added to standard therapy.9 However, the duration of beneficial effect of reduced mortality could not be assessed because the benefit of enalapril in NYHA class I to III HF was not evaluated, and follow-up data are limited. The average age of patients in the study was 71 years, and individuals with significant comorbidities were excluded.
ACE inhibitors also were found to reduce mortality even in asymptomatic patients with HFrEF in the Studies of Left Ventricular Dysfunction trial (SOLVD).10 Enalapril was found to reduce 4-year mortality by 16% and decrease HF hospitalizations when added to conventional therapy consisting primarily of digitalis, diuretics, and nitrates in patients with HFrEF. In this trial, patients aged ≥ 80 years were excluded as well as those with serum creatinine > 2 mg/dL or other conditions that could shorten survival or otherwise impede participation in a long-term trial.
PARADIGM-HF trial patients with HFrEF were randomized to enalapril or the angiotensin receptor-neprilysin inhibitor LCZ696. After a median of 27 months of follow-up, treatment with the angiotensin receptor-neprilysin inhibitor demonstrated greater reduction in CV mortality and HF hospitalizations than enalapril did and was associated with reduced all-cause mortality.11 The trial was stopped early because of evidence of overwhelming benefit with LCZ696. This study of mainly white men included no patients aged ≥ 75 years.