Effect of the angiotensin-receptor-neprilysin inhibitor in heart failure patients with left ventricular ejection fraction higher than 40%

The angiotensin-receptor-neprilysin inhibitor (ARNI) reduced cardiovascular deaths and heart failure hospitalization in patients with heart failure of reduced ejection fraction (HFrEF). Its role in non-HFrEF patients was not clear. This study aims to answer this question. In this retrospective study, we enrolled 928 patients diagnosed with non-HFrEF, 492 of them received angiotensin converting enzyme inhibitor (ACEI) and the rest 436 received angiotensin-receptor-neprilysin inhibitor. Outcomes were compared by Kaplan-Meier survival analysis and various clinical parameters were investigated using Cox multivariable analysis, followed by interaction analysis. Minnesota living with heart failure Questionnaire (MLHFQ) was employed as one of the criteria to assess heart failure outcome. The cardiovascular (CV) death or HF hospitalization at 24 months occurred in 49 patients in ACEI group compared with 31 in ARNI group (Hazard Ratio (HR): 1.231, 95% confidence Interval (CI): 1.080–2.460, P = .031). And ARNI showed better prognosis of HF hospitalization (HR: 1.283, 95%CI: 1.065–1.360, P = .038). Cumulative Kaplan-Meier estimates of endpoints, ARNI could reduce the incidence of CV death or HF hospitalization (P = .042) and HF hospitalization (P = .035). The stratified analysis revealed that participants with age less than 70 years old had a lower incidence of CV death or HF hospitalization (HR: 1.194, 95%CI: 1.011–1992, P = .031) after treated with ARNI. Patients received diuretics could benefit from ARNI (HR: 1.383, 95%CI: 1.082–1.471, P = .019). Similar results were also observed in patients with heart rate lower than 90 bpm (HR: 1.556, 95%CI: 1.045–2.386, P = .003) and patients with atrial fibrillation history (HR: 1.873, 95%CI: 1.420–2.809, P = .011). ARNI could improve the quality of life both from the total, emotional and physical aspects. ARNI is an efficacy treatment strategy to improve the outcome and quality of life in patients with non-HFrEF.