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

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.

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, 9030 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.

In this large nationwide cohort of AF-naive 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.