BACKGROUND: The global use of angiotensin receptor neprilysin inhibitor (ARNI) in clinical practice, especially in patients with heart failure and below-normal ejection fraction (HFbnEF), has not been thoroughly evaluated. We aimed to investigate the characteristics, outcomes, and adverse events in patients treated with ARNI for HF with reduced (HFrEF), below-normal (HFbnEF), and supranormal left ventricular EF (HFsnEF). METHODS: This observational study analyzed data from the electronic healthcare records (EHR) of patients with HF treated with ARNI between 2015 and 2022 in North and South America, Europe, the Middle East, Africa, and Asia-Pacific. Based on the left ventricular EF, patients were categorized as HFrEF (<
40%), HFbnEF (40-60%), and HFsnEF (>
60%). Mortality and the incidence of adverse events were investigated. RESULTS: Of the 11,141 patients analyzed, HFrEF, HFbnEF and HFsnEF accounted for 74%, 22%, and 4%, respectively. Patients with a higher EF were more likely to be older, female, and obese. Hypertension and atrial fibrillation were the most common in HFsnEF. Systolic blood pressure was lower and natriuretic peptide levels were higher in the lower EF groups. Mortality was lowest in HFbnEF (7.7 per 100 patient-years follow-up in HFrEF, 5.8 in HFmrEF, and 6.0 in HFsnEF). Similarly, hypotension and acute kidney injury were the least frequent in HFbnEF. Incidence of elevated serum potassium levels was similar between the groups. CONCLUSIONS: In this analysis of large-scale EHR, ARNI was mainly used in HFrEF and HFbnEF, consistent with previous randomized trials and pooled analyses. Adverse events were less common in HFbnEF.