Early Rhythm Control Therapy for Atrial Fibrillation in Low-Risk Patients A Nationwide Propensity Score-Weighted Study

Background: Rhythm control is associated with lower risk for adverse cardiovascular outcomes compared with usual care among patients recently diagnosed with atrial fibrillation (AF) with a CHA₂DS₂-VASc score of approximately 2 or greater in EAST-AFNET 4 (Early Treatment of Atrial Fibrillation for Stroke Prevention Trial). Objective: To investigate whether the results can be generalized to patients with low stroke risk. Design: Population-based cohort study. Setting: Nationwide claims database of the Korean National Health Insurance Service. Participants: 54 216 patients with AF having early rhythm control (antiarrhythmic drugs or ablation) or rate control therapy that was initiated within 1 year of the AF diagnosis. Measurements: The effect of early rhythm control on the primary composite outcome of cardiovascular death, ischemic stroke, hospitalization for heart failure, or myocardial infarction was compared between eligible and ineligible patients for EAST-AFNET 4 (CHA₂DS₂-VASc score, approximately 0 to 1) using propensity overlap weighting. Results: In total, 37 557 study participants (69.3%) were eligible for the trial (median age, 70 years; median CHA₂DS₂-VASc score, 4), among whom early rhythm control was associated with lower risk for the primary composite outcome than rate control (hazard ratio, 0.86 [95% CI, 0.81 to 0.92]). Among the 16 659 low-risk patients (30.7%) who did not meet the inclusion criteria (median age, 54 years; median CHA₂DS₂-VASc score, 1), early rhythm control was consistently associated with lower risk for the primary outcome (hazard ratio, 0.81 [CI, 0.66 to 0.98]). No significant differences in safety outcomes were found between the rhythm and rate control strategies regardless of trial eligibility. Limitation: Residual confounding. Conclusion: In routine clinical practice, the beneficial association between early rhythm control and cardiovascular complications was consistent among low-risk patients regardless of trial eligibility.