Target-Dose Versus Below-Target-Dose ACE Inhibitors and Lower Risk of Kidney Failure in U.S. Veterans with HFrEF

Authors

• Amiya A. Ahmed, Veterans Affairs Medical Center, Washington, DC, USA.
• Frederick Lu, Veterans Affairs Medical Center, Washington, DC, USA.
• Sijian Zhang, Brown University, Providence, RI, USA.
• Venkatesh K. Raman, Veterans Affairs Medical Center, Washington, DC, USA.
• Samir S. Patel, Veterans Affairs Medical Center, Washington, DC, USA.
• Charity J. Morgan, Veterans Affairs Medical Center, Washington, DC, USA.
• Charles Faselis, Veterans Affairs Medical Center, Palo Alto, CA, USA.
• Phillip H. Lam, Georgetown University, Washington, DC, USA.
• Gregg C. Fonarow, University of California, Los Angeles, CA, USA.
• Paul A. Heidenreich, Veterans Affairs Medical Center, Palo Alto, CA, USA.
• Tariq Ahmad, Yale University, New Haven, CT, USA.
• Stefan D. Anker, Charité Universitätsmedizin, Berlin, Germany.
• Marco Metra, University of Brescia, Brescia, Italy.
• Bertram Pitt, University of Michigan, Ann Arbor, MI, USA.
• Javed Butler, Baylor Scott and White Research Institute, Dallas, TX, USA.
• Andrew R. Zullo, Brown University, Providence, RI, USA.
• Hans J. Moore, Veterans Affairs Medical Center, Washington, DC, USA.
• Jose D. Vargas, Veterans Affairs Medical Center, Washington, DC, USA.
• Cherinne Arundel, Veterans Affairs Medical Center, Washington, DC, USA.
• Carlos Andrés Sánchez-Vallejo, University of the Andes, Bogota, Colombia.
• Prakash Deedwania, Veterans Affairs Medical Center, Washington, DC, USA.
• Helen M. Sheriff, Veterans Affairs Medical Center, Washington, DC, USA.
• Qing Zeng-Treitler, Veterans Affairs Medical Center, Washington, DC, USA.
• Wen-Chih Wu, Brown University, Providence, RI, USA.
• Ali Ahmed, Veterans Affairs Medical Center, Washington, DC, USA.

Document Type

Journal Article

Publication Date

3-9-2026

Journal

European journal of heart failure

DOI

10.1093/ejhf/xuag076

Abstract

AIMS: In patients with heart failure with reduced ejection fraction (HFrEF), target-dose (vs. below-target-dose) angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) improve clinical outcomes but worsen kidney function. Less is known about their effect on kidney failure (KF), especially in those with advanced chronic kidney disease (CKD), the examination of which was the objective of our study. METHODS AND RESULTS: Of the 154,945 Veterans with HFrEF (EF≤40%) and no baseline KF, 134,046 were initiated on ACEIs (target-dose, n=37,667) and 20,899 were initiated on ARBs (target-dose, n=4017) during 2000-2018. While remaining blinded to study outcomes, we assembled two propensity score-matched cohorts: ACEI (N=70,860; target-dose, n=35,430) and ARB (N=7900; target-dose, n=3950), balanced on 76 baseline characteristics. Hazard ratios (95% CIs) associated with target doses were estimated for 5-year KF and all-cause mortality, up to December 31, 2023. In the ACEI cohort, target-dose was associated with a 18% lower risk of KF (HR, 0.82; 95% CI, 0.75-0.89) and a 6% lower risk of death (HR, 0.94; 95% CI, 0.92-0.97). Subgroup and spline analyses showed that while the KF association was significant for those with baseline eGFR <35 ml/min/1.73m2, the mortality association was significant for those with eGFR ≥35 ml/min/1.73m2. In the ARB cohort, target-dose had no association with outcomes. CONCLUSIONS: In patients with HFrEF, target-dose (vs. below-target-dose) ACEIs, but not ARBs, were associated with lower risk of KF, which was significant in those with advanced CKD. The survival benefit was modest and limited to those without advanced CKD.

APA Citation

Ahmed, Amiya A.; Lu, Frederick; Zhang, Sijian; Raman, Venkatesh K.; Patel, Samir S.; Morgan, Charity J.; Faselis, Charles; Lam, Phillip H.; Fonarow, Gregg C.; Heidenreich, Paul A.; Ahmad, Tariq; Anker, Stefan D.; Metra, Marco; Pitt, Bertram; Butler, Javed; Zullo, Andrew R.; Moore, Hans J.; Vargas, Jose D.; Arundel, Cherinne; Sánchez-Vallejo, Carlos Andrés; Deedwania, Prakash; Sheriff, Helen M.; Zeng-Treitler, Qing; Wu, Wen-Chih; and Ahmed, Ali, "Target-Dose Versus Below-Target-Dose ACE Inhibitors and Lower Risk of Kidney Failure in U.S. Veterans with HFrEF" (2026). GW Authored Works. Paper 8919.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/8919

Department

Medicine