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

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.

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.

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; p = 0.016) and an absolute risk reduction of 11.17% (95% CI 5.81%-17.36%; p < 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%; p = 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; p < 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; p = 0.002).

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.

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.