Nearly half of all patients presenting with heart failure have normal or near normal left ventricular systolic function.\u00a0 Optimal treatment strategies for this large patient group remain unclear.\u00a0 Small mechanistic studies have suggested diastolic function may be improved by mineralocorticoid-receptor antagonists.\u00a0 Whether this mechanistic benefit translates into better patient outcomes is not known.\u00a0 In the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial, 3445 patients with heart failure and an ejection fraction of 45% or more were randomised in a double-blind fashion to either spironolactone (15 to 45 mg daily) or placebo.\u00a0 The primary outcome was a composite of death from cardiovascular causes, aborted cardiac arrest, or hospitalization for the management of heart failure with patients.\u00a0 Over a mean follow-up period of 3.3 years, the primary outcome occurred in 18.6% of the spironolactone group and 20.4% of the placebo group (HR, 0.89; 95% CI, 0.77 to 1.04; P=0.14).\u00a0 Compared with placebo, spironolactone resulted in a statistically significant reduction in hospitalizations for heart failure (206 patients vs. 245 patients, HR, 0.83; 95% CI, 0.69 to 0.99, P=0.04).\u00a0 Use of spironolactone came at a cost of increased rates of hyperkaliemia (18.7%, vs. 9.1%), but no differences in serious adverse events.<\/p>\n
Conclusions<\/strong><\/p>\n In this large randomised controlled trial of patients with heart failure and preserved systolic function, the mineralocorticoid receptor antagonist spironolactone failed to result in patient benefit aside from a reduction in heart failure hospitalizations.\u00a0 Whether the reduction in hospitalizations with spironolactone represents a mechanistic benefit, or just better volume control achieved through diuresis, is unclear.\u00a0 Therapies that clearly improve outcomes in patients with heart failure and preserved ejection fraction remain elusive.<\/p>\n