Influence of Age on the Efficacy and Safety of Spironolactone in Heart Failure with Preserved Ejection Fraction

Abstract

Introduction Heart failure with preserved ejection fraction (HFpEF) disproportionately affects older adults. Age-related changes in physiology and variable pharmacokinetics may affect drug efficacy and safety among older individuals. We examined efficacy and safety of spironolactone by age in the Americas region (N=1767) of the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial. Methods TOPCAT was an international, multicenter, prospective, randomized trial that enrolled patients with HF and left ventricular ejection fraction ≥ 45%, age 50 or older with eGFR ≥ 30ml/min/1.73 m2 and prior HF hospitalization or elevated natriuretic peptide levels. Participants were randomized to spironolactone or placebo over a mean follow up of 3.3 years. We assessed treatment effect (primary study composite of CV death, aborted cardiac arrest, and hospitalization for HF) and safety (permanent study medication discontinuation due to hyperkalemia, rise in serum creatinine to ≥ 3.0 mg/dL, gynecomastia, or allergic reaction or intolerance) by age categories ( Results Number of participants were 492, 555, and 720 in the Conclusions In patients with HFpEF, the efficacy of spironolactone was consistent across age categories, but treatment-related adverse events were more common in participants age 65 or older. These data support guideline recommendations for use of spironolactone in appropriately selected HFpEF regardless of age, but underscore that closer laboratory surveillance is critical in older individuals.