European journal of heart failure · 2026
Target-Dose Versus Below-Target-Dose ACE Inhibitors and Lower Risk of Kidney Failure in U.S. Veterans with HFrEF.
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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, Ahmed Ali
Аннотация
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.
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.