The role of
spironolactone and
eplerenone in patients with
Heart Failure with preserved Ejection Fraction (HFpEF) is not well defined. Since a growing medical literature has suggested that
mineralocorticoid receptor antagonists may be beneficial for patients with HFpEF, this review gives an in-depth update on the role of
spironolactone and
eplerenone and their implications for
therapy in the setting of HFpEF. Eleven clinical studies, including seven randomized trials, were reviewed. Two randomized controlled trials evaluated the effect of
eplerenone on different end-points, including 6 minute walk distance (6 MWD), cardiovascular mortality, non-fatal reinfarction, hospitalization for
unstable angina and
congestive heart failure.
Eplerenone did not affect either 6 MWD or event-free survival rates in the overall study population in these two reports. The effects of
spironolactone on similar composite endpoints were evaluated in 7 studies in patients with HFpEF. Compared to placebo, hospitalization for
heart failure was significantly lower in the
spironolactone group and
spironolactone was also shown to improve diastolic function and induced beneficial remodeling through a reduction in myocardial
fibrosis. The safety profile of
spironolactone and
eplerenone has been assessed in two recent studies. Data showed that
eplerenone and
spironolactone are both associated with the occurrence of
gynecomastia,
mastodynia, and abnormal
vaginal bleeding and in addition, they can increase natriuresis and cause renal retention of
potassium; furthermore,
eplerenone may cause
hyperkalemia and promote the onset of
metabolic acidosis or
hyponatremia. In conclusion although the
mineralocorticoid receptor antagonists eplerenone and
spironolactone improve clinical outcomes in patients with HFrEF, additional data will be necessary to better define their risk-benefit profile, especially for
eplerenone, in the treatment of HFpEF.