Spironolactone is used in heart failure with reduced ejection fraction (HFrEF) beyond its diuretic effect. The key additional pharmacological benefit in heart failure is:

• A It blocks beta-adrenergic receptors in the myocardium, reducing sympathetic-mediated cardiac remodelling
• B It competitively antagonises aldosterone at mineralocorticoid receptors in the heart, fibroblasts, and vessels, reducing pathological cardiac fibrosis, hypertrophy, and remodelling ✓
• C It inhibits ACE in the myocardium, reducing local angiotensin II levels and preventing direct cardiotoxicity
• D It activates natriuretic peptide receptors in the myocardium, improving ventricular relaxation and reducing filling pressures

Explanation

In heart failure, circulating aldosterone and local myocardial aldosterone activate mineralocorticoid receptors in cardiac fibroblasts, driving collagen synthesis, myocardial fibrosis, and cardiac hypertrophy — independent of volume status. Spironolactone (and eplerenone) block mineralocorticoid receptors throughout the cardiovascular system, reducing these non-renal maladaptive responses. Clinical trials (RALES for spironolactone, EPHESUS for eplerenone) demonstrated mortality reduction in HFrEF beyond diuresis, confirming the cardioprotective anti-fibrotic mechanism as the primary benefit.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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Written and medically reviewed by the StethoPrep medical team.