A 65-year-old man has HFrEF (EF 32%), NYHA Class III, on optimised GDMT (ACEI, carvedilol, spironolactone). He remains symptomatic with NT-proBNP 3200 pg/mL. His carvedilol dose is maximal. What is the next medication to add per current guidelines?

• A Digoxin for rate control
• B Switch ACEI to sacubitril/valsartan (ARNI) — PARADIGM-HF trial showed mortality benefit over enalapril ✓
• C Add amlodipine as an afterload-reducing agent
• D Add ivabradine if resting HR ≥ 70 bpm in sinus rhythm — also add dapagliflozin (SGLT2i)

Explanation

In HFrEF patients who remain symptomatic on maximally tolerated ACEI/ARB + beta-blocker + MRA, switching ACEI to the ARNI sacubitril/valsartan is recommended (AHA/ESC Class I). PARADIGM-HF demonstrated a 20% relative risk reduction in CV death/HF hospitalisation vs enalapril. To prevent angioedema, a 36-hour washout period is required when switching from ACEI to sacubitril/valsartan. Additionally, SGLT2 inhibitors (dapagliflozin/empagliflozin) are now Class I recommendations for all HFrEF patients regardless of diabetes, based on DAPA-HF and EMPEROR-Reduced trials. Ivabradine (if HR ≥ 70 bpm in sinus rhythm on maximised beta-blocker) is a further add-on.

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

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Written and medically reviewed by the StethoPrep medical team.