Spironolactone did not significantly reduce deaths in patients with heart failure and preserved ejection fraction, however it did cut hospitalisations for heart failure, the TOPCAT study has shown.

This was an international, multicentre, randomised, double-blind trial of patients with symptomatic heart failure and left ventricular ejection fraction ≥ 45%. A total of 3,445 patients were randomised to receive either spironolactone (15 to 45 mg daily) or placebo. The mean age of patients was 68.7 in both groups.

The primary outcome was a composite of death from cardiovascular causes, aborted cardiac arrest, or hospitalisation for the management of heart failure. Mean follow-up was 3.3 years. The primary outcome occurred in 320 (18.6%) of the 1,722 patients in the spironolactone group and 351 (20.4%) of the 1,723 patients in the placebo group; hazard ratio (HR) 0.89 (95% CI:0.77-1.04; P = 0.14).

However, there was a significant fall in the incidence of hospitalisation for heart failure in the spironolactone group, 206 patients (12.0%) vs 245 (14.2%) in the placebo group; HR 0.83 (95% CI:0.69-0.99, P = 0.04).

In terms of adverse outcomes, spironolactone was associated with increased serum creatinine levels, and a doubling of the rate of hyperkalaemia,  18.7% compared with 9.1% in the placebo group, but reduced hypokalemia. With frequent monitoring, there were no significant differences in the incidence of serious adverse events.

The authors conclude that in patients with heart failure and a preserved ejection fraction, adding spironolactone to existing therapy did not significantly reduce the incidence of the primary composite outcome of death from cardiovascular causes, aborted cardiac arrest, or hospitalisation for the management of heart failure.

Mineralocorticoid-receptor antagonists (MRAs) such as spironolactone and eplerenone improve the prognosis for patients with heart failure and a reduced left ventricular ejection fraction. However, it would appear that MRAs are not as effective in those patients with preserved ejection fraction.

Perhaps we can take some encouragement from the reduction in hospitalisations for heart failure as this is a key component in the cost-effective management of this patient group and in an area with little in the way of meaningful therapeutic interventions this trial may at least give us another option.

Dr Peter Savill