Spironolactone-related Adverse Events Higher in Older HFpEF Patients

Age was a factor in spironolactone-related adverse events in older patients with heart failure with preserved ejection fraction (HFpEF) new study results suggest.

“HFpEF disproportionately affects older adults,” the authors wrote. “Age-related changes in physiology and variable pharmacokinetics may affect drug efficacy and safety among older individuals.”

The study, presented at the Heart Failure Society of America Scientific Meeting in Philadelphia and published in the meeting supplement of the Journal of Cardiac Failure, looked at data on patients from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial. TOPCAT was a multicenter, international, prospective, randomized trial that included 492, 555, and 720 participants in the <65, 65-74, and ≥75 age categories, respectively. Participants had an eGFR ≥30mL/min/1.73 m² and a prior hospitalization for heart failure or elevated natriuretic peptide levels. Patients were randomly assigned to receive either spironolactone or placebo, with a mean follow-up of 3.3 years. The primary study outcome was a composite of cardiovascular death, aborted cardiac arrest, and heart failure hospitalization. Participants in the older category tended to be female, Caucasian, and with a lower body mass index and eGFR compared to other younger categories.

After multivariable adjustment, spironolactone efficacy on the composite study outcome was similar across age groups compared to placebo (overall HR=0.83; 95% CI, 0.70 to 0.99; P=0.038), but there was an increased risk of the composite safety endpoint in patients taking spironolactone compared to those taking placebo (HR=2.55; 95% CI, 1.91 to 3.39; P<0.001), and the interaction was more pronounced in older patients (P-interaction=0.01).

“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,” the authors concluded in their study. “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.”

Vardeny O, Vaduganathan M, Claggett B, et al. J Card Fail. 2019;25(8):S12. Abstract 027.