Spironolactone Adverse Events Increased in Older Heart Failure Patients

Orly Vardeny, PharmD

A new post hoc analysis found safety disparities among older adult age groups with heart failure with preserved ejection fraction (HFpEF) when administered spironolactone, but no difference in the drug’s efficacy.

In a new study presented at the Heart Failure Society of America (HFSA) 2019 Scientific Sessions in Philadelphia, PA, Orly Vardeny, PharmD, of the University of Minnesota Medical School, presented findings showing the potassium-sparing diuretic may put older HFpEF patients at risk for adverse events regardless of lessened dosing regimens.

Vardeny and colleagues used data from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) study—an international, prospective, randomized, double-blind trial comparing spironolactone to placebo in 3445 patients with HFpEF.

Patients were aged 50 years or older with at least 1 symptom and 1 sign of chronic HF, left ventricular ejection fraction of 45% or greater, controlled systolic blood pressure, and serum potassium levels less than 5 mEq/L.

Investigators limited participant assessment to patients enrolled in the Americas region (n= 1767). They assessed for a pair of primary endpoints designed to indicate efficacy and safety: composite of cardiovascular death, aborted cardiac arrest, and hospitalization for HF; and the discontinuation of study medication due to hyperkalemia, worsening renal function, gynecomastia, or intolerance.

Patients were subcategorized by 3 age groups: <65 years (n= 492); 65-74 years (n= 555), or ≥75 (n= 720). They were randomized to either 15 mg daily spironolactone—with an option to increase every 4 weeks over 4 months, up to 45 mg&mdash;or placebo.

Vardeny explained HFpEF “indiscriminately affects” older adult patients, and given clinical evidence indicating a potential altered response to standard therapy, the team wanted to examine the overall effect of spironolactone by age category.

The observed patient population was 49.9% female, mostly white, with a high rate of HF hospitalization and comorbid conditions including atrial fibrillation.

The adjusted incidence rates of the primary composite outcome of cardiovascular death, aborted cardiac arrest, and hospitalization for HF, per 100 patients-years, were lower in each of the treated patient age groups (8.7; 12.7; 14.5) than that of the equivalent placebo groups (12.1; 13.6; 15.3).

All-cause mortality rates, which increased gradually among the older age groups, were also generally lower for treated patients (4.4; 6.0; 9.0) than for patients on placebo (4.4; 8.1; 10.1). Vardeny observed the efficacy benefits were most pronounced among the older patients.

However, rates for hyperkalemia (5.6; 13.5; 12.2) worsening renal function (7.4; 7.3; 6.7), and hypotension (12.0; 19.4; 13.4) were more significant among a majority of the treated age groups than their respective placebo-treated counterparts.

Observing the adverse events were spiked among treated patients aged 65-74 years old, Vardeny noted older patients were more likely to discontinue therapy, if not lower their dosing regimen.

Though there was no heterogeneity among rates of primary efficacy endpoint in patient age groups, investigators were able to conclude there were notable differences in safety outcomes among older HFpEF patients treated with spironolactone. She advised such findings come into consideration when prescribing older, at-risk patients with HF.

“When we have an older patient in front of us, I think we’re trying to find out whether a therapy has been observed in an older patient population, and whether it’s safe in older adults,” she said.

The study, “Influence of Age on the Efficacy and Safety of Spironolactone in Heart Failure with Preserved Ejection Fraction,” was presented at HFSA 2019.