Early Rhythm Control vs Usual Care After Acute Ischemic Stroke in Patients With Atrial Fibrillation

Early rhythm control reduces cardiovascular events in patients with atrial fibrillation (AF); however, its effectiveness in the setting of acute ischemic stroke remains uncertain. We aimed to examine whether early rhythm control after acute ischemic stroke is associated with a lower risk of recurrent stroke or systemic embolism (SE) in patients with AF.

This nationwide cohort study used the DeSC-IQVIA integrated database, an administrative claims database covering approximately 16 million individuals in Japan. Adults hospitalized for acute ischemic stroke with AF present at admission between 2014 and 2025 were included. The exposure was initiation of rhythm control (antiarrhythmic drugs, catheter ablation, or electrical cardioversion) within 8 weeks of admission (early rhythm control) vs no initiation (usual care), assessed at a landmark. The primary outcome was hospitalization for recurrent ischemic stroke or SE. Secondary outcomes included major bleeding, heart failure (HF) hospitalization, and all-cause mortality. Baseline differences were adjusted using propensity score overlap weighting. Cause-specific hazard ratios (HRs), cumulative incidence with death as a competing risk, and risk differences at 5 years were estimated.

Among 14,355 patients who survived event-free through the 8-week landmark (median age, 83 years [IQR, 78-88]; 6,935 [48.3%] women), 268 (1.9%) received early rhythm control. During 23,583 person-years, early rhythm control was associated with a lower risk of stroke/SE (HR, 0.56; 95% CI 0.32-0.97; weighted 5-year cumulative incidence, 8.0% vs 13.8%; risk difference, -5.9 percentage points [95% CI -11.0 to 0.8]). Among secondary outcomes, no association was observed with major bleeding (HR, 1.44; 95% CI 0.74-2.82) or HF hospitalization (HR, 0.73; 95% CI 0.39-1.38); early rhythm control was associated with lower all-cause mortality (HR, 0.72; 95% CI 0.53-0.97). Results were consistent across landmark periods of 4-24 weeks.

In this nationwide cohort study, early rhythm control after acute ischemic stroke in patients with AF was associated with a reduced risk of recurrent stroke or SE. These findings suggest that early rhythm control may serve as an additional secondary prevention strategy for ischemic stroke, with flexible timing of initiation. These observational findings are hypothesis-generating and warrant confirmation in randomized controlled trials.