Mineralocorticoid Receptor Antagonists: The Pillar Drug in Heart Failure

Mineralocorticoid receptor antagonists (MRAs) have emerged as a cornerstone in the pharmacological management of heart failure (HF), particularly in patients with reduced ejection fraction (HFrEF). By antagonizing the effects of aldosterone, MRAs mitigate fluid retention, myocardial fibrosis, and neurohormonal activation, key contributors to HF progression. Steroidal MRAs, including spironolactone and eplerenone, have demonstrated significant clinical efficacy in landmark trials such as Randomized Aldactone Evaluation Study (RALES), Eplerenone Postacute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS), and Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF), showing reductions in mortality, hospitalizations, and symptomatic burden. Spironolactone, though potent, is associated with hormonal side effects due to its nonselective receptor binding, while eplerenone offers improved tolerability through greater receptor specificity. This review explores the pharmacological mechanisms, clinical trial evidence, and safety considerations of steroidal MRAs, underscoring their indispensable role in comprehensive HF therapy.