Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are key components of guideline-directed therapy for heart failure with reduced ejection fraction (HFrEF). Concerns remain regarding potential kidney function decline with higher doses of these therapies, particularly among patients with chronic kidney disease (CKD). A large observational cohort study published in the European Journal of Heart Failure evaluated the association between target-dose therapy and long-term risk of kidney failure (KF) and mortality.

The study included 154,945 Veterans with HFrEF (ejection fraction ≤40%) without baseline KF who initiated treatment between 2000 and 2018. Among them, 134,046 received ACEIs and 20,899 received ARBs. Propensity score matching created balanced cohorts including 70,860 ACEI users (35,430 receiving target doses) and 7,900 ARB users (3,950 receiving target doses), matched across 76 baseline characteristics. Outcomes were assessed over five years, with hazard ratios estimated for KF and all-cause mortality.

In the ACEI cohort, target-dose therapy was associated with an 18% lower risk of KF compared with below-target doses (hazard ratio [HR] 0.82; 95% CI 0.75-0.89) and a modest 6% lower risk of death (HR 0.94; 95% CI 0.92-0.97). Subgroup analyses showed the KF risk reduction was significant in patients with baseline estimated glomerular filtration rate (eGFR) <35 mL/min/1.73 m², whereas the mortality association was observed primarily in those with eGFR ≥35 mL/min/1.73 m². In contrast, target-dose ARBs were not associated with significant differences in KF or mortality outcomes.

Target-dose ACEI therapy was associated with lower KF risk in patients with HFrEF. The mortality association was modest and differed according to baseline kidney function.