Background: Ablation of atrial fibrillation can restore normal heart rhythm, but its effect on clinical outcomes is uncertain.

Purpose: To determine the effect of ablation on ischemic stroke at more than 30 days (primary outcome).

Data sources: Search of 9 databases without language restrictions from 1 January 1987 to 13 September 2024, and bridge search of 2 databases to 1 May 2025.

Study selection: Randomized controlled trials of catheter or surgical ablation versus no ablation that had at least 1 month of follow-up and reported stroke and/or mortality.

Data extraction: Dual independent data extraction and risk-of-bias assessment.

Data synthesis: Compared with medical therapy, catheter ablation reduced risks for ischemic stroke after 30 days (relative risk [RR], 0.63 [95% CI, 0.43 to 0.92]), mortality (RR, 0.73 [CI, 0.60 to 0.88]), and heart failure (HF) hospitalization (RR, 0.68 [CI, 0.55 to 0.85]). However, catheter ablation increased the RR for ischemic stroke at or before 30 days (6.81 [CI, 1.56 to 29.8]) such that the RRs were 0.77 (CI, 0.55 to 1.09) for any ischemic stroke and 0.77 (CI, 0.57 to 1.05) for all strokes. Surgical ablation reduced the RRs for ischemic stroke (0.54 [CI, 0.34 to 0.86]) and stroke from any cause (0.54 [CI, 0.35 to 0.82]) but had uncertain benefit for other outcomes; RRs were 0.63 (CI, 0.37 to 1.06) for ischemic stroke after 30 days, 0.90 (CI, 0.70 to 1.15) for mortality, and 0.90 (CI, 0.60 to 1.35) for HF hospitalization.

Limitations: Clinical heterogeneity of trials, lack of participant-level data, and inclusion of unblinded trials.

Conclusion: Catheter ablation reduced the risks for ischemic stroke at more than 30 days, mortality, and HF hospitalization. Surgical ablation had uncertain benefit, except for stroke.

Primary funding source: National Center for Advancing Translational Sciences of the National Institutes of Health (Awards TL1TR002344 and UL1TR002345).

PROSPERO: CRD42023409751