Switching to angiotensin receptor–neprilysin inhibitor and reduced risk of new-onset atrial fibrillation in heart failure with reduced ejection fraction: a nationwide propensity score–matched study

AIMS: We investigated whether switching from traditional renin-angiotensin system (RAS) blockade to angiotensin receptor-neprilysin inhibitor (ARNI) is associated with a lower risk of new-onset atrial fibrillation (AF) than continuing RAS blockade in patients with heart failure with reduced ejection fraction (HFrEF) without prior AF. METHODS AND RESULTS: Using data from the Korean National Health Insurance Service (2017-2021), we identified 39,061 patients with HFrEF without prior AF who received either ARNI (n = 12,263) or traditional RAS blockade (n = 26,798). After 1:1 propensity score matching, 9,030 patients were included in each group. The primary outcome was new-onset AF within 1 year. In the propensity score-matched cohort, new-onset AF incidence was lower in the ARNI group (10.73 vs. 12.15 per 100 person-years; hazard ratio [HR] 0.89; 95% confidence interval [CI] 0.81-0.98; P = 0.021). The composite outcome (new-onset AF, ischaemic stroke, or all-cause death) was also reduced (HR 0.85; 95% CI 0.79-0.92; P < 0.001). In competing risk analysis, ARNI was associated with a lower subdistribution hazard of new-onset AF (sHR 0.73; 95% CI 0.58-0.91; P = 0.005). In the unmatched cohort, the HR was 0.85 (95% CI 0.75-0.96) in an exploratory model including age, sex, hypertension, chronic kidney disease, prior ischaemic stroke, socioeconomic status, residential region, and beta-blocker use, and 0.94 (95% CI 0.87-1.02) after adjustment for all measured baseline covariates. CONCLUSION: In this large nationwide cohort of AF-naïve patients with HFrEF, switching to ARNI was associated with a lower risk of short-term new-onset AF than continuing traditional RAS blockade. As this was a retrospective study, further prospective studies are needed to confirm these findings.