A 70-year-old woman with heart failure with reduced ejection fraction (LVEF 25%) and persistent NYHA class II symptoms is started on spironolactone 25 mg daily. What is the primary mechanism by which spironolactone reduces mortality in this population?

• A Natriuresis via inhibition of the Na-K-2Cl cotransporter in the loop of Henle
• B Mineralocorticoid receptor antagonism reducing myocardial fibrosis ✓
• C Inhibition of the renin-angiotensin-aldosterone system at the ACE level
• D Sympatholysis via central alpha-2 agonism

Explanation

Spironolactone is a mineralocorticoid receptor antagonist that reduces mortality in severe HFrEF (RALES trial) primarily by blocking aldosterone-mediated myocardial fibrosis, sodium retention, and potassium loss. Unlike loop diuretics, it does not act on the Na-K-2CL cotransceptor. Eplerenone is the more selective alternative used post-MI in HFrEF.

Reference: Harrison's Principles of Internal Medicine, 21st ed.

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Written and medically reviewed by the StethoPrep medical team.