Association Between Angiotensin Receptor-Neprilysin Inhibitor Use and Clinical Outcomes in Concurrent Heart Failure with Reduced Ejection Fraction and End-Stage Renal Disease

Background Although angiotensin receptor-neprilysin inhibitor (ARNI) therapy has been shown to improve outcomes in heart failure with reduced ejection fraction (HFrEF), its benefits in patients with end-stage renal disease (ESRD) on dialysis remain uncertain. This study investigated the clinical outcomes of ARNI compared to renin-angiotensin system (RAS) blockers in HFrEF patients with concomitant ESRD on dialysis. Methods Using the Korean National Health Insurance Service database, we identified individuals with HFrEF and ESRD on dialysis who were prescribed either ARNI or RAS blockers between 2017 and 2021. After applying inverse probability of treatment weighting, we compared 2,104 patients on ARNI with 2,191 on RAS blockers. The primary endpoint was a composite of all-cause mortality and any hospitalization over 2 years. Results Baseline characteristics were balanced between the groups. ARNI use was associated with a significantly lower risk of the primary endpoint (hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.75–0.97) compared to RAS blockers. Additionally, ARNI was associated with a lower risk of all-cause mortality (HR 0.68, 95% CI 0.54–0.86) and any hospitalization (HR 0.86, 95% CI 0.75–0.98). Subgroup analyses demonstrated consistent associations between ARNI use and reduced risk across all subgroups (age, sex, comorbidities, and medications). Good adherence to ARNI was associated with a lower risk of the primary outcome, whereas non-adherence showed no such benefit. Conclusion In a real-world population with HFrEF and ESRD on dialysis, ARNI use was associated with a lower risk of all-cause mortality and hospitalization compared to RAS blockers, particularly in those with good adherence to therapy. Abstract Figure Graphical Abstract. Association between Angiotensin Receptor-Neprilysin Inhibitor Use and Clinical Outcomes in Patients with Concurrent Heart Failure with Reduced Ejection Fraction and End-Stage Renal Disease on Dialysis In this real-world study of patients with heart failure with reduced ejection fraction (HFrEF) and end-stage renal disease (ESRD) on dialysis, the use of angiotensin receptor-neprilysin inhibitor (ARNI) was associated with a significant reduction in the risk of all-cause mortality and any hospitalization compared to renin-angiotensin system (RAS) blockers. These benefits were particularly evident in patients who adhered well to their medication.