Angiotensin receptor‐neprilysin inhibitors in concurrent heart failure with reduced ejection fraction and kidney failure

Abstract Aims Angiotensin receptor‐neprilysin inhibitor (ARNI) therapy has demonstrated improved outcomes in heart failure with reduced ejection fraction (HFrEF). However, its benefits in patients with concomitant kidney failure undergoing replacement therapy remain uncertain. Methods and results Using the National Health Insurance Service database, we identified individuals with HFrEF and kidney failure receiving replacement therapy who were prescribed either ARNI or renin‐angiotensin system (RAS) blockers between 2017 and 2021. After applying inverse probability of treatment weighting, we compared 2104 patients on ARNI with 2191 on RAS blockers. The primary endpoint was a composite of all‐cause mortality and any hospitalization. Secondary endpoints included all‐cause mortality, any hospitalization and cardiovascular mortality. During a median follow‐up of 19.1 months, 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 with RAS blockers. ARNI also showed a reduced risk of all‐cause mortality (HR 0.68, 95% CI 0.54–0.86), any hospitalization (HR 0.86, 95% CI 0.75–0.98) and cardiovascular mortality (HR 0.68, 95% CI 0.52–0.89). Subgroup analyses demonstrated consistent associations across age, sex, comorbidities and medications. Good adherence to ARNI was linked to a lower risk of the primary outcome, whereas non‐adherence showed no benefit. Conclusions Among HFrEF patients with kidney failure receiving replacement therapy, ARNI use was associated with lower risks of all‐cause mortality, any hospitalization and cardiovascular mortality compared with RAS blockers, particularly in those with good adherence to therapy.