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

Amiya A Ahmed1,2, Frederick Lu1,3, Sijian Zhang3

  • 1Veterans Affairs Medical Center, Washington, DC, USA.

European Journal of Heart Failure
|March 9, 2026
PubMed

Insights

Target-dose angiotensin-converting enzyme inhibitors (ACEIs) reduced kidney failure risk in heart failure patients, especially those with advanced chronic kidney disease (CKD). The survival benefit was modest and seen in patients without advanced CKD.

Area of Science:

  • Cardiology
  • Nephrology
  • Pharmacology

Background:

  • Heart failure with reduced ejection fraction (HFrEF) patients often have co-existing chronic kidney disease (CKD).
  • Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are standard treatments for HFrEF, improving outcomes but potentially affecting kidney function.
  • The impact of target-dose ACEIs and ARBs on kidney failure (KF) in HFrEF patients, particularly those with advanced CKD, requires further investigation.

Purpose of the Study:

  • To evaluate the association of target-dose ACEIs and ARBs with the risk of kidney failure (KF) and all-cause mortality in patients with HFrEF.
  • To examine these associations specifically in patients with advanced chronic kidney disease (CKD).

Main Methods:

  • A retrospective cohort study of 154,945 Veterans with HFrEF (EF≤40%) and no baseline KF was conducted.
  • Two propensity score-matched cohorts (ACEI and ARB) were assembled to compare target-dose versus below-target-dose initiations.
  • Outcomes of 5-year KF and all-cause mortality were estimated using hazard ratios.

Main Results:

  • In the ACEI cohort, target-dose was associated with an 18% lower risk of KF and a 6% lower risk of death.
  • The KF risk reduction with target-dose ACEIs was significant in patients with baseline eGFR <35 ml/min/1.73m2 (advanced CKD).
  • The mortality benefit from target-dose ACEIs was significant in patients with eGFR ≥35 ml/min/1.73m2, but target-dose ARBs showed no significant association with outcomes.

Conclusions:

  • Target-dose ACEIs, but not ARBs, were associated with a reduced risk of kidney failure (KF) in HFrEF patients, particularly those with advanced CKD.
  • A modest survival benefit was observed with target-dose ACEIs, limited to patients without advanced CKD.
  • These findings suggest a potential benefit of optimizing ACEI dosing for kidney protection in HFrEF patients with advanced CKD.
Abstract

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