• Marjorie Flores Chang, Rohan Samson, Amitabh Pandey, and Thierry H Le Jemtel.
• Section of Cardiology, John W. Deming Department of Medicine, Tulane University School of Medicine, 1430 Tulane Avenue, SL-48, New Orleans, LA 70112, United States.
• Am. J. Med. Sci. 2025 Jan 31.

AbstractData from pivotal randomized controlled trials established the four pillars of guideline-directed medical therapy in heart failure with reduced ejection fraction. The randomized controlled trials enrolled stable patients with New York Heart Association functional class II-III and a low incidence of cardiovascular death and hospitalization for heart failure. Whether the four pillars retain therapeutic value when a patient's symptoms worsen and life expectancy decreases has received scarce attention. We review the observational studies that point to the fading benefit of neurohormonal modulation and cardiac afterload reduction in the late stages of cardiovascular or renal diseases. We then propose a pragmatic approach for collecting evidence-based data on sequential withdrawal of the four pillars in patients with heart failure and reduced ejection fraction after years of guideline-directed medical therapy.Copyright © 2025. Published by Elsevier Inc.

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