Initiating early rhythm control therapy within 8 weeks of admission for acute ischemic stroke in patients with atrial fibrillation is associated with a reduced risk of recurrent ischemic stroke or systemic embolism compared to usual care, according to a nationwide retrospective cohort study published on October 21 in Neurology.
Study Analyzes Acute Ischemic Stroke Patients over Eight Weeks
The research examined 14,355 adults hospitalized for acute ischemic stroke who had atrial fibrillation present at admission, drawing from Japan’s DeSC-IQVIA integrated claims database from 2014 to 2025. The median age of the cohort was 83 years, and 48.3% were women. At the 8-week mark, investigators classified patients into two distinct groups: those who received early rhythm control therapy—incorporating antiarrhythmic drugs, catheter ablation, or electrical cardioversion—and those who received usual care without rhythm control therapy.
Out of the total cohort, 268 patients received early rhythm control, while 14,087 received usual care. Tracking major clinical endpoints, the investigators found that early rhythm control therapy was linked to a lower risk for recurrent ischemic stroke or systemic embolism, registering a hazard ratio of 0.56 with a 95% confidence interval ranging from 0.32 to 0.97. The weighted 5-year cumulative incidence stood at 8.0% for the treatment group compared to 13.8% for the usual care group, yielding a risk difference of -5.9 percentage points.
Early Rhythm Control Therapy Reduces All Cause Mortality
Beyond reducing secondary strokes, the therapy showed a measurable link to lower all-cause mortality. The hazard ratio for death from any cause was 0.72, with a 95% confidence interval of 0.53 to 0.97. The weighted 5-year cumulative incidence for all-cause mortality reached 24% in the early rhythm control group versus 40% in the usual care group, marking a risk difference of -15.9 percentage points. However, the intervention showed no link to major bleeding or heart failure hospitalizations.
The study’s findings remained consistent when researchers tested alternative landmark periods of 4, 12, and 24 weeks. Subgroup analyses suggested more pronounced risk reduction among patients who presented without intracranial or extracranial artery stenosis, where the hazard ratio was 0.36 (95% CI, 0.17-0.76).
Practical Implications in Stroke Prevention
Standard protocols dictate that individuals suffering an ischemic stroke receive anticoagulants to prevent subsequent clotting. This new data suggests an additional pathway for intervention.
People who have an ischemic stroke are prescribed anticoagulants, medications that stop the blood from clotting easily, to prevent a second stroke. Our study suggests that early rhythm control may serve as another prevention strategy, with flexible timing of initiation, within eight weeks of stroke.
That observation came from corresponding investigator Yuichi Imanaka, MD, MPH, PhD, of Kyoto University in Japan, during a press release detailing the findings led by Shuhei Egashira of the same institution’s Graduate School of Medicine.
Methodological Limitations
Despite the broad scope of the claims database, the study carries notable limitations. The early rhythm control group was small, which limits precision when projecting long-term outcomes. Treatment crossover and time-dependent confounding after the landmark were not fully addressed. Researchers also lacked access to granular clinical variables within the claims data, including stroke severity, functional status, imaging findings, echocardiographic parameters, and AF burden. Consequently, residual confounding from unmeasured factors could not be fully excluded, and adverse effects of rhythm control could not be reliably ascertained. Because the cohort included predominantly older Japanese adults, the generalizability of these findings remains constrained. The study was funded by the Japan Society for the Promotion of Science.
