Spironolactone in heart failure reduces mortality primarily by blocking:

• A RAAS-mediated potassium wasting that would otherwise trigger fatal arrhythmias
• B Aldosterone-stimulated collagen synthesis in renal tubular cells
• C Angiotensin-converting enzyme to reduce afterload on the failing heart
• D Mineralocorticoid receptors in the heart and blood vessels, preventing aldosterone-mediated cardiac fibrosis and remodelling independent of its natriuretic effect ✓

Explanation

In the RALES trial, spironolactone reduced all-cause mortality by 30% in severe heart failure. Beyond potassium-sparing diuresis, aldosterone itself (elevated in heart failure) activates mineralocorticoid receptors in myocardial fibroblasts, promoting collagen deposition and cardiac fibrosis — worsening remodelling. Spironolactone blocks these cardiac and vascular aldosterone effects, reducing fibrosis and improving cardiac function. Its relatively modest diuretic effect is not the primary mortality benefit.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.