Little benefit of spironolactone for heart failure with preserved ejection fraction

Treatment with spironolactone doesn’t improve overall outcomes for heart failure patients with preserved left ventricular function, reports a trial in the New England Journal of Medicine.

The Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial included 3445 patients with symptomatic heart failure but an ejection fraction of 45 percent or higher. They were randomly assigned to double-blinded treatment with spironolactone, 15 to 45 mg/d, or placebo, added to existing therapy. A composite outcome of death resulting from cardiovascular causes, aborted cardiac arrest, or hospitalization for heart failure was assessed at a mean follow-up time of 3.3 years.

A primary outcome event occurred in 18.6 percent of patients receiving spironolactone and 20.4 percent with placebo. The difference was not significant; incidence rates were 5.9 and 6.6 events per 100 person-years, respectively. The rate of hospitalization for heart failure was lower in the spironolactone group: 12.0 versus 14.2 percent, hazard ratio 0.83.

The rates of all-cause mortality and hospitalization were also similar between groups. Patients receiving spironolactone had higher rates of increased serum creatinine and hyperkalemia but a lower rate of hypokalemia. There were no differences in serious adverse events, including serum creatinine of 3.0 mg/dL or higher or dialysis. The authors note that the study protocol included frequent patient monitoring.

For patients with heart failure and left ventricular dysfunction, mineralocorticoid-receptor antagonists reduce the risk of death and heart failure hospitalization.Some studies have reported that these drugs improve diastolic function in heart failure patients with preserved ejection fraction.

However, the TOPCAT trial found no overall reduction in cardiovascular outcomes with spironolactone added to existing therapy in this group of patients. The results suggest some reduction in hospitalization for heart failure in patients treated with spironolactone. In treated patients, close monitoring is warranted because of the heightened risk of hyperkalemia and increased creatinine levels [Pitt B, et al. Spironolactone for heart failure with preserved ejection fraction. N Engl J Med 2014; 370:1383–1392].