Left atrial appendage closure versus oral anticoagulants in atrial fibrillation: updated evidence from a systematic review and meta-analysis

Background Oral anticoagulants (OAC) are the cornerstone for stroke prevention in atrial fibrillation (AF), but long-term adherence and bleeding risk remain major limitations. Left atrial appendage closure (LAAC) provides a non-pharmacological alternative; however, comparative outcome data across study designs are inconsistent. We assessed the efficacy and safety of LAAC versus OAC in AF. Methods We performed a systematic search of PubMed, Embase, Cochrane Library, and Web of Science up to 30 September 2025 for randomized trials and propensity score–matched studies comparing LAAC with OAC in AF. Random-effects models were used to pool relative risks (RR) with 95% confidence intervals (CI). Prespecified outcomes included a composite endpoint, stroke outcomes, mortality, and major bleeding. Results Fifteen studies (4 randomized trials and 11 propensity-matched studies) comprising 17,116 patients were included. Compared with OAC, LAAC significantly reduced the composite endpoint (RR 0.79, 95% CI 0.66–0.95; p=0.010) and was associated with marked reductions in all-cause mortality (RR 0.58, 95% CI 0.49–0.69; p<0.001) and cardiovascular mortality (RR 0.55, 95% CI 0.44–0.67; p<0.001). Rates of any stroke (RR 1.06, 95% CI 0.86–1.31), ischemic stroke (RR 1.00, 95% CI 0.85–1.17) and hemorrhagic stroke (RR 0.96, 95% CI 0.54–1.70) were comparable between strategies. Major bleeding showed a non-significant trend favoring LAAC (RR 0.84, 95% CI 0.67–1.04; p=0.112). Conclusion Across randomized and propensity-matched evidence, LAAC is associated with significant reductions in mortality and composite clinical outcomes compared with OAC, while maintaining similar stroke risk. LAAC may represent a favorable alternative for selected AF patients, particularly when long-term anticoagulation is challenging.