Higher Risk of Kidney Failure Associated with Angiotensin Receptor Blockers Versus ACE Inhibitors in Patients with Heart Failure

Hans J. Moore, Department of Medicine, Veterans Affairs Medical Center, Washington, DC; Department of Medicine, George Washington University, Washington, DC; Department of Medicine, Georgetown University, Washington, DC; Department of Medicine, Uniformed Services University, Washington, DC.
Wen-Chih Wu, Department of Medicine, Veterans Affairs Medical Center, Providence, RI; Department of Medicine, Brown University, Providence, RI.
Paul A. Heidenreich, Department of Medicine, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA; Department of Medicine, Stanford University, Stanford, CA.
Patrick Rossignol, Clinical Investigation Centre, University of Lorraine, Nancy, France.
Samir S. Patel, Department of Medicine, Veterans Affairs Medical Center, Washington, DC; Department of Medicine, George Washington University, Washington, DC.
Frederick Lu, Department of Medicine, Veterans Affairs Medical Center, Providence, RI; Department of Medicine, Brown University, Providence, RI.
Phillip H. Lam, Department of Medicine, Georgetown University, Washington, DC; Department of Cardiology, Medstar Washington Hospital Center, Washington, DC.
Amiya A. Ahmed, Department of Medicine, Yale University, New Haven, CT; Department of Medicine, Veterans Affairs Medical Center, West Haven, CT.
Charles Faselis, Department of Medicine, Veterans Affairs Medical Center, Washington, DC; Department of Medicine, George Washington University, Washington, DC; Department of Medicine, Uniformed Services University, Washington, DC.
Javed Butler, Baylor Scott and White Research Institute, Dallas, TX; Department of Medicine, University of Mississippi, Jackson, MS.
Carlos E. Palant, Department of Medicine, George Washington University, Washington, DC.
Bertram Pitt, Department of Medicine, University of Michigan, Ann Arbor, MI.
Matthew R. Weir, Department of Medicine, University of Maryland, Baltimore, MD.
Prakash Deedwania, Department of Medicine, Veterans Affairs Medical Center, Washington, DC; Department of Medicine, University of California, San Francisco, CA.
David Atkins, Department of Medicine, Veterans Affairs Medical Center, Washington, DC; Department of Medicine, George Washington University, Washington, DC.
Venkatesh K. Raman, Department of Medicine, Veterans Affairs Medical Center, Washington, DC; Department of Medicine, Georgetown University, Washington, DC.
Janani Rangaswami, Department of Medicine, Veterans Affairs Medical Center, Washington, DC; Department of Medicine, George Washington University, Washington, DC.
Jose D. Vargas, Department of Medicine, Veterans Affairs Medical Center, Washington, DC; Department of Medicine, Georgetown University, Washington, DC.
Sijian Zhang, Department of Medicine, Veterans Affairs Medical Center, Washington, DC.
Charity J. Morgan, Department of Medicine, Veterans Affairs Medical Center, Washington, DC; Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL.
Helen M. Sheriff, Department of Medicine, Veterans Affairs Medical Center, Washington, DC; Department of Medicine, George Washington University, Washington, DC.
Qing Zeng-Treitler, Department of Medicine, Veterans Affairs Medical Center, Washington, DC; Department of Medicine, George Washington University, Washington, DC.
Gregg C. Fonarow, Department of Medicine, University of California, Los Angeles, CA.
Ali Ahmed, Department of Medicine, Veterans Affairs Medical Center, Washington, DC; Department of Medicine, George Washington University, Washington, DC; Department of Medicine, Georgetown University, Washington, DC. Electronic address: ali.ahmed@va.gov.

Document Type

Journal Article

Publication Date

5-24-2025

Journal

The American journal of medicine

DOI

10.1016/j.amjmed.2025.05.024

Keywords

ACE Inhibitors; Angiotensin Receptor Blockers; Heart Failure; Kidney Failure

Abstract

BACKGROUND: Renin-angiotensin system (RAS) inhibition with angiotensin-covering enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) is associated with a lower risk of kidney failure in patients with heart failure. We examined whether this association varies between ACEIs and ARBs. METHODS: From 300,361 Veterans with heart failure without kidney failure initiated on ACEIs (n=256,224) or ARBs (n=44,137), we assembled a propensity score-matched cohort of 88,178 patients while remaining blinded to study outcomes. Hazard ratio (95% CI) for 5-year kidney failure in patients in the ARB group was estimated. Kidney failure was defined as receipt of kidney replacement therapy or persistent drop in baseline estimated glomerular filtration rate (eGFR) to <15 mL/min/1.73m. RESULTS: Matched patients had mean age 71 years, ejection fraction 44%, eGFR 70 mL/min/1.73m, 97% were male, 18% African American, 23% received ACEIs or ARBs in high doses, and were balanced on 76 baseline characteristics. Kidney failure occurred in 4.4% (1961/44,089) and 5.4% (2389/44,089) of the patients in the ACEI and ARB groups, respectively. When accounted for the competing risk of death, patients in the ARB group had a 20% (95% CI, 13-28%) higher risk of kidney failure, which was similar in low-dose and high-dose subgroups. The associated risk of death was 5% (95% CI, 3-7%) lower in the ARB group, which was only significant in the low-dose group (7% vs 0%; interaction p, 0.007). CONCLUSION: In patients with heart failure, ARBs (vs. ACEIs) are associated with a higher risk of incident kidney failure. These findings need to be confirmed in future clinical trials.

Department

Medicine

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