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Aldosterone-receptor antagonists have proven to be effective in patients with heart failure and reduced ejection fraction. However, their role in heart failure patients with preserved ejection fraction (HF-PEF) is still controversial. Three recent randomized clinical trials were recently published to address this controversy (1,2,3). Kanan and colleagues assembled a cohort from OPTIMIZE-HF (Organized Program to Initiate Lifesaving Treatment in Hospitalized Patient with Heart Failure) database; primary composite endpoint of all-cause mortality was followed over 2.4 years. Aldosterone-receptor antagonists had no effects on all-cause mortality (HR: 1.03; 95% CI: 0.89 to 1.20; p=0.693). Another multicenter, prospective, randomized, double-blind trial, Aldosterone Receptor Blockade in Diastolic Heart Failure (Aldo-DHF), evaluated two equally ranked co-primary endpoints, changes in diastolic dysfunction (E/e) on echocardiogram and maximal exercise capacity (peak Vo2) on cardiopulmonary exercise testing. After 12 months E/e decreased from 12.7 ± 3.6 to 12.1 ± 3.7 with spironolactone and increased from 12.8 ± 4.8 to 13.6 ± 4.3 with placebo (adjusted mean differences, -1.5, 95% CI, -2.0 to –9.0; p<.001). Peak Vo2 did not significantly change with spironolactone vs. placebo (from 16.3 ± 3.6 ml/min/kg to 16.8 ± 4.6 ml/kg/min and from 16.4 ± 3.5 ml/min/kg to 16.9 ± 4.4 ml/min/kg; respectively), adjusted mean difference, +0.1 ml/min/kg; 95% CI, - 0.6 to + 0.8ml/min/kg; p=.81). These results indicate improvement in diastolic function without significant change in maximal exercise capacity. In the TOPCAT trial (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone-receptor antagonists), a randomized double-blind trial, the primary outcome was composite of death from cardiovascular causes, aborted cardiac arrest, or hospitalization for the management of heart failure was followed for 3.3 years. Hospitalization due to heart failure was significantly less in the spironolactone group than in the placebo group (12.0% vs. 14.2%; hazard ratio, 0.83; 95% CI, 0.69 to 0.99, p=0.04).


The results from the three trials showed no effect on mortality with the use of aldosterone-receptor antagonists in patients with HF-PEF. There was some improvement in left ventricular function in one trial while no effect on hospitalization and maximal exercise capacity were apparent.

1. Patel K, et al. Aldosterone Antagonists and Outcomes in Real-World Older Patients with Heart Failure and Preserved Ejection Fraction. JACC Heart Fail. 2013;1(1):40–47.   [PubMed: 23814702]
2. Edelmann F, et al. Effect of Spironolactone on Diastolic Function and Exercise Capacity in Patients with Heart Failure with Preserved Ejection Fraction. JAMA 2013;309(8):781-791.   [PubMed: 23443441]
3. Pitt B, et al. Spironolactone for Heart Failure with Preserved Ejection Fraction. N Engl J Med. 2014;370:1383-1392   [PubMed: 24716680]

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