Early Catheter Ablation for Patients With Atrial Fibrillation and a Stroke History: A Target Trial Emulation Analysis.

Abstract (English)

BACKGROUND AND OBJECTIVES: Atrial fibrillation (AF) is a major contributor to ischemic stroke, yet evidence on whether catheter ablation improves outcomes in patients with AF and a history of stroke remains limited. We emulated a target trial using observational data to estimate the effect of early catheter ablation vs medical therapy on clinical outcomes in this high-risk population. METHODS: We retrospectively included patients aged 18-85 years with AF and a history of ischemic stroke from 6 Chinese centers between January 2019 and December 2024. The primary outcome was major adverse cardiovascular events (MACEs). Secondary outcomes included all-cause rehospitalization, cardiovascular rehospitalization, all-cause death, and functional and cognitive outcomes assessed by modified Rankin Scale (mRS) and post hoc AD8 scores. A cloning-censoring-weighting approach was used to emulate a target trial comparing early ablation (within a 1-year grace period) and medical therapy in time-dependent outcomes, using weighted Kaplan-Meier curves. Restricted mean survival time (RMST) was used when the proportional hazards assumption was violated. mRS and AD8 were assessed after propensity score matching. RESULTS: A total of 431 patients were included (median age, 70 years; 37% female), of whom 207 underwent early catheter ablation. The median follow-up was 3.0 years. At 36 months, early ablation was associated with a gain of 1.54 MACE-free months (95% CI 0.40-2.85; <i>p</i> = 0.016) and an absolute risk reduction of 11.17% (95% CI 5.81%-17.36%; <i>p</i> < 0.001). Cardiovascular rehospitalization showed a higher 36-month event-free survival rate in the ablation group (absolute difference 11.98%; 95% CI 2.26%-21.44%; <i>p</i> = 0.018). In the matched cohort (n = 250), ablation was associated with better mRS scores (adjusted odds ratio 0.31; 95% CI 0.19-0.51; <i>p</i> < 0.001) and, in a post hoc cognitive assessment using AD8, lower odds of cognitive impairment (adjusted odds ratio 0.42; 95% CI 0.24-0.72; <i>p</i> = 0.002). DISCUSSION: In this target trial emulation analysis, catheter ablation was associated with a modestly lower long-term risk of MACE in patients with AF and a stroke history. Secondary analyses suggested exploratory associations between ablation and lower long-term cardiovascular rehospitalization, and better neurologic and cognitive outcomes. Major limitations include the retrospective design and potential residual confounding. Randomized trials with larger sample sizes are warranted. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that early catheter ablation in adult patients with AF and a history of ischemic stroke decreases the risk of MACEs compared with guideline-directed medical therapy.