Butt, Mohammad Omer

ABSTRACT Background Oral anticoagulation (OAC) remains the cornerstone of stroke prevention in atrial fibrillation (AF) but is limited by bleeding risk. Left atrial appendage occlusion (LAAO) devices offer an alternative; however, recent randomized trials have reported inconsistent efficacy compared with OAC. Methods We conducted a systematic review and meta‐analysis of randomized controlled trials (RCTs) comparing LAAO with OAC through April 1, 2026, using MEDLINE, EMBASE, and Cochrane CENTRAL. Eligible studies enrolled adults (≥18 years) with AF randomized to LAAO or OAC. Primary and secondary outcomes were pooled as risk ratios (RR) with 95% confidence intervals (CIs). Individual patient‐level data (IPD) were reconstructed from published Kaplan–Meier curves for time‐to‐event sensitivity analyses. Results Six RCTs ( n = 7,004; mean age 72 years; CHA 2 DS 2 ‑VASc 3.9; HAS‑BLED 1.7; mean follow‐up 38 months) were included. LAAO showed no significant difference in ischemic stroke (RR 1.20, 95% CI 0.82–1.76), major bleeding (RR 0.77, 95% CI 0.50–1.17), or all‐cause mortality (RR 0.96, 95% CI 0.82–1.13) compared with OAC. Hemorrhagic stroke risk was significantly lower with LAAO (RR 0.53, 95% CI 0.30–0.93). Reconstructed IPD demonstrated similar stroke and bleeding risks (HR 1.24 and 0.84, respectively) but lower all‐cause mortality with LAAO (HR 0.70, 95% CI 0.52–0.95). Conclusion LAAO provides comparable ischemic stroke prevention and major bleeding outcomes to OAC and reduces hemorrhagic stroke risk. Reconstructed IPD analyses suggest a possible mortality benefit that warrants further investigation. Future studies using contemporary devices and post‐ablation populations are needed to refine patient selection and further characterize the comparative clinical outcomes of LAAO and OAC in AF patients.