A 55-year-old man has HFrEF (LVEF 30%) on optimal tolerated ACEi and beta-blocker therapy. He remains NYHA Class III. The RALES trial informs adding which drug to his regimen?

• A Spironolactone (mineralocorticoid receptor antagonist) ✓
• B Hydralazine + isosorbide dinitrate
• C Digoxin
• D Calcium channel blocker (amlodipine)

Explanation

The RALES trial established that spironolactone (25–50 mg/day) added to ACEi + loop diuretic in severe HFrEF (EF <35%, NYHA III–IV) reduced all-cause mortality by 30% and HF hospitalization. Mineralocorticoid receptor antagonists (spironolactone, eplerenone) are Class I recommendation for HFrEF. The EMPHASIS-HF trial confirmed eplerenone benefit in milder HFrEF (NYHA II). Hydralazine + ISDN (A-HeFT) is recommended for African-American patients intolerant of RAAS inhibitors. Digoxin reduces hospitalization but not mortality (DIG trial). CCBs generally worsen outcomes in HFrEF except amlodipine (neutral).

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

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Written and medically reviewed by the StethoPrep medical team.