Eplerenone Revisited: A Balanced Reappraisal of Its Role in Hypertension, Heart Failure, and Cardiorenal Disease

Mineralocorticoid receptor activation contributes to cardiovascular and kidney injury through inflammation, fibrosis, oxidative stress, endothelial dysfunction, and adverse tissue remodeling. Eplerenone, a selective steroidal mineralocorticoid receptor antagonist developed to minimize the endocrine adverse effects associated with spironolactone, has demonstrated substantial clinical benefits in patients with post–myocardial infarction left ventricular dysfunction and heart failure with reduced ejection fraction, where its role is well established. This review examines the evolving evidence supporting eplerenone across cardiovascular and renal diseases, including hypertension, left ventricular hypertrophy, albuminuria, and broader cardiorenal risk reduction. Although accumulating data suggest potential benefits in these settings, the strength of evidence varies considerably across indications. Spironolactone remains the mineralocorticoid receptor antagonist with the strongest evidence for resistant hypertension, whereas finerenone has generated the most robust dedicated kidney outcomes data in patients with diabetic chronic kidney disease. We conclude that eplerenone should be viewed neither as simply an alternative for spironolactone intolerance nor as a universal substitute for newer mineralocorticoid receptor antagonists. Rather, it remains an evidence-based, well-tolerated therapy with a firmly established role in post–myocardial infarction left ventricular dysfunction and heart failure with reduced ejection fraction, together with a potentially valuable role in selected hypertensive and cardiorenal populations where selective mineralocorticoid receptor blockade and long-term tolerability are important clinical considerations.