A 58-year-old man with HFrEF (LVEF 30%), NYHA class III, already on maximally tolerated doses of ACE inhibitor, carvedilol, and mineralocorticoid antagonist, has NT-proBNP 3400 pg/mL. He is euvolemic. The PARADIGM-HF trial demonstrated benefit of which add-on treatment?

• A Adding spironolactone to the existing ACE inhibitor
• B Adding hydralazine-isosorbide dinitrate to the existing therapy
• C Replacing the ACE inhibitor with sacubitril/valsartan (ARNI) ✓
• D Adding digoxin for additional rate control

Explanation

The PARADIGM-HF trial (NEJM 2014) demonstrated that sacubitril/valsartan (Entresto) — an ARNI combining neprilysin inhibitor + ARB — reduced CV death and HF hospitalization by 20% compared to enalapril in HFrEF patients. Per current guidelines (AHA/ACC 2022), sacubitril/valsartan is a Class I recommendation to replace ACE inhibitor or ARB in HFrEF patients who remain symptomatic on optimal background therapy. There must be a 36-hour washout after stopping ACEi before starting sacubitril/valsartan to prevent angioedema. Adding MRA to ACEi is already done; digoxin has no mortality benefit.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.