Eplerenone is preferred over spironolactone in male patients with heart failure with reduced ejection fraction (HFrEF) because:

• A Eplerenone is more selective for the mineralocorticoid receptor with negligible affinity for androgen and progesterone receptors, avoiding gynaecomastia and sexual dysfunction in men ✓
• B Eplerenone has more potent mineralocorticoid receptor blockade at lower doses
• C Eplerenone inhibits aldosterone synthesis rather than blocking its receptor
• D Eplerenone crosses the blood-brain barrier and reduces central sympathetic activation, providing additional benefit

Explanation

Spironolactone is a non-selective mineralocorticoid receptor antagonist with significant binding to androgen (causing anti-androgenic effects — gynaecomastia, impotence, decreased libido) and progesterone receptors (causing menstrual irregularities). Eplerenone has ~1000-fold lower affinity for androgen and progesterone receptors compared to mineralocorticoid receptors, making it highly selective and avoiding sexual side effects. Both drugs have similar survival benefits in HFrEF (RALES trial for spironolactone, EPHESUS for eplerenone). Eplerenone does not inhibit aldosterone synthesis.

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

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Written and medically reviewed by the StethoPrep medical team.