Angiotensin-converting enzyme inhibitors vs. receptor blockers in heart failure with mildly reduced ejection fraction

Evidence regarding the prognostic impact of angiotensin-converting enzyme inhibitors (ACEi) vs. receptor blockers (ARB) in heart failure with mildly reduced ejection fraction (HFmrEF) is limited.

We retrospectively studied consecutive patients hospitalized with HFmrEF from 2016 until 2022 at a German university hospital. The prognostic impact of treatment with ACEi compared with ARB was investigated regarding the primary endpoint of all-cause mortality at 30 months. The key secondary endpoint was heart failure (HF)-related rehospitalization.

A total of 1,551 patients discharged on renin-angiotensin system inhibitors (ACEi: n = 1,055; ARB: n = 496) were included. Patients treated with ARB were older and had a higher burden of comorbidities. All-cause mortality at 30 months occurred in 251/1,055 (23.8%) patients treated with ACEi and in 147/496 (29.6%) patients treated with ARB [unadjusted hazard ratio [HR] = 0.762, 95% confidence interval [CI] 0.622-0.934; log-rank p = 0.009]. After multivariable adjustment, ACEi were still associated with improved long-term survival (adjusted HR = 0.786, 95% CI: 0.625-0.989; p = 0.040). This association was still found after propensity score matching (n = 440 per group) (23.2% vs. 29.5%; HR = 0.749, 95% CI: 0.578-0.971; p = 0.029). In contrast, the risk of HF-related rehospitalization at 30 months did not differ between the two groups in the unmatched cohort (12.7% vs. 14.5%; HR = 0.849, 95% CI: 0.638-1.130; p = 0.262) and after propensity score matching (16.1% vs. 14.8%; HR = 1.080, 95% CI: 0.772-1.512; p = 0.653).

In patients hospitalized with HFmrEF, ACEi therapy was associated with reduced 30-month all-cause mortality compared with ARB, whereas the risk of HF-related rehospitalization did not differ.