A 58-year-old man with HFrEF (EF 30%) is already on maximally tolerated ACE inhibitor, beta-blocker, and spironolactone. He remains symptomatic (NYHA III) and his NT-proBNP remains markedly elevated. Per PARADIGM-HF trial evidence and current guidelines, the most appropriate next drug class to add is:

• A Digoxin for additional symptomatic benefit
• B Sacubitril-valsartan (ARNI — angiotensin receptor-neprilysin inhibitor) ✓
• C Hydralazine-isosorbide dinitrate combination
• D Ivabradine, provided heart rate > 70 bpm and sinus rhythm

Explanation

The PARADIGM-HF trial demonstrated that sacubitril-valsartan reduced cardiovascular mortality and hospitalisation by 20% compared to enalapril in patients with HFrEF (EF ≤40%), NYHA II–IV. Current guidelines recommend switching from an ACE inhibitor (after a 36-hour washout) to sacubitril-valsartan in patients who remain symptomatic on optimised therapy. Ivabradine is appropriate if HR >70 bpm in sinus rhythm but the question targets the most impactful addition, which is the ARNI.

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

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Written and medically reviewed by the StethoPrep medical team.