Mineralocorticoid receptor antagonists in heart failure with preserved ejection fraction (HFpEF)

Int J Cardiol. 2015 Dec 1;200:15-9. doi: 10.1016/j.ijcard.2015.07.038.


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.

Keywords: Aldosterone; Eplerenone; HFpEF; Heart failure; Spironolactone.

Publication types

  • Review

MeSH terms

  • Eplerenone
  • Heart Failure / drug therapy*
  • Heart Failure / physiopathology
  • Humans
  • Mineralocorticoid Receptor Antagonists / adverse effects
  • Mineralocorticoid Receptor Antagonists / therapeutic use*
  • Randomized Controlled Trials as Topic
  • Spironolactone / adverse effects
  • Spironolactone / analogs & derivatives*
  • Spironolactone / therapeutic use*
  • Stroke Volume / drug effects*
  • Stroke Volume / physiology*


  • Mineralocorticoid Receptor Antagonists
  • Spironolactone
  • Eplerenone