Clinical outcomes of sacubitril/valsartan in patients with mildly reduced or preserved ejection fraction and acute heart failure: a multi-institutional study.

BACKGROUND

The long-term real-world effectiveness and safety of in-hospital initiation of sacubitril/valsartan in patients hospitalized for acute heart failure (HF) with mildly reduced or preserved left ventricular ejection fraction (HFmrEF or HFpEF) remain uncertain, particularly among patients with advanced chronic kidney disease or dialysis, who are often underrepresented in randomized trials.

PATIENTS/MATERIALS AND

METHODS

We identified 9,107 patients with HFmrEF or HFpEF hospitalized for acute HF from the Chang Gung Research Database between January 1, 2016, and June 30, 2023. Propensity score weighting with overlap weights was applied to balance baseline characteristics between treatment groups. Risks of fatal and nonfatal outcomes were analyzed using Cox proportional hazards and Fine-Gray subdistribution hazard models, respectively.

RESULTS

After overlap weighting, the incidence rates of the composite endpoint of HF rehospitalization and cardiovascular (CV) death were 39.7 and 40.3 per 100 person-years in the angiotensin receptor neprilysin inhibitor (ARNI) and angiotensin receptor blocker (ARB) groups, respectively (Hazard ratio, 0.97; 95% confidence interval, 0.79-1.20). In analyses stratified by chronic kidney disease stage, the association between treatment group and the primary endpoint was consistent among patients with eGFR ≥60, 30-59, <30 mL/min/1.73 m2, or dialysis.

CONCLUSIONS

In this multi-institutional real-world cohort of patients hospitalized for acute HF with left ventricular ejection fraction (LVEF) >40%, in-hospital initiation of sacubitril/valsartan was not associated with lower risks of HF rehospitalization or CV death compared with ARB therapy, despite greater NT-proBNP reduction in a biomarker subcohort. Limited sample size precludes definitive conclusions regarding therapeutic equivalence.