Long-term efficacy and safety of left atrial appendage closure vs. oral anticoagulation in atrial fibrillation: a meta-analysis of randomized controlled trials

Aims Left atrial appendage closure (LAAC) has emerged as an alternative to oral anticoagulation (OAC) for stroke prevention in atrial fibrillation (AF), but its long-term comparative efficacy remains uncertain. This systematic review and meta-analysis evaluated randomized controlled trials (RCTs) comparing LAAC with OAC in AF. Methods and results MEDLINE, Embase, Scopus, and the Cochrane Database of Systematic Reviews were searched through 8 April 2026. Risk ratios (RR) with 95% confidence intervals (CI) were pooled using random-effects models. Certainty of evidence (CoE) was assessed using GRADE. Six RCTs involving 7004 participants were included (3681 assigned to LAAC and 3323 to OAC). Compared with OAC, LAAC resulted in a significantly higher risk of ischaemic stroke or systemic embolism (134 vs. 80 events; RR 1.41, 95% CI 1.07–1.86; moderate CoE). No significant differences were observed for any stroke or systemic embolism (RR 1.10, 95% CI 0.87–1.39; moderate CoE), all-cause mortality (RR 0.92, 95% CI 0.77–1.10; high CoE), cardiovascular mortality (RR 0.90, 95% CI 0.67–1.21; moderate CoE), non-cardiovascular mortality (RR 0.92, 95% CI 0.75–1.12; moderate CoE), major bleeding (RR 0.91, 95% CI 0.77–1.08; high CoE), or haemorrhagic stroke (RR 0.58, 95% CI 0.28–1.17; moderate CoE). LAAC reduced the risk of nonprocedural clinically relevant bleeding compared with OAC (RR 0.50, 95% CI 0.43–0.59; high CoE). Conclusion In patients with AF, LAAC results in a higher risk of ischaemic stroke or systemic embolism than an OAC-based strategy. Compared with OAC, LAAC has no effect on major bleeding or mortality and does not reduce haemorrhagic stroke.