Patient selection for mineralocorticoid receptor antagonists in heart failure with mildly reduced or preserved ejection fraction

Pharmacotherapy. 2023 Jun;43(6):563-569. doi: 10.1002/phar.2801. Epub 2023 Apr 18.


The mineralocorticoid receptor is a steroid hormone receptor that contributes to cardiac tissue inflammation, fibrosis, and cardiac dysfunction and plays an important role in the pathophysiology of heart failure. Mineralocorticoid receptor antagonists (MRA) are an important component of guideline-directed medical therapy for heart failure to improve clinical outcomes. Clinical trial evidence in heart failure with reduced ejection fraction (HFrEF) informed a strong guideline recommendation for use of MRA in symptomatic patients, barring contraindications. In heart failure with mildly reduced ejection fraction (HFmrEF) and in heart failure with preserved ejection fraction (HFpEF), data are less robust, and this drug class received a weaker recommendation in the heart failure treatment guidelines. Thus, careful selection of patients with HFmrEF/HFpEF who are most likely to benefit from MRA is paramount to better optimize use of these medications. The purpose of this narrative review is to outline the rationale for the use of MRA in heart failure, summarize the clinical trial evidence for MRA in HFmrEF/HFpEF, discuss clinical considerations for their use, and describe investigations of nonsteroidal MRA in HFmrEF/HFpEF.

Keywords: eplerenone; heart failure; heart failure with mildly reduced ejection fraction; heart failure with preserved ejection fraction; mineralocorticoid receptor antagonists; spironolactone.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Heart Failure* / drug therapy
  • Humans
  • Mineralocorticoid Receptor Antagonists / therapeutic use
  • Patient Selection
  • Prognosis
  • Stroke Volume / physiology


  • Mineralocorticoid Receptor Antagonists