Long-Term Clinical Outcomes of Left Atrial Appendage Closure Versus Oral Anticoagulation in Atrial Fibrillation: An Updated Meta-Analysis and Trial Sequential Analysis
Faiqa Farooq, Syeda Irza Fatima, Muhammad Maaz Amjad, Aleena Amir Malik, Tayyaba Ikram Qazi, Hamza Wazir Khan, Hira Niazi, Pari Kotak, Aimen Rahat, Amir Hamza Khan, Muaz Shehzar Bashir, Aqeel Abbas, Muhammad Hamza Riaz Malik, Laiba Wahab, Muhammad Muzamil Shaikh, Wareesha Memon, Sajjad Khan, Asia Batool, Muhammad Huzaifa Khattak, Bilal Wazir KhanLeft atrial appendage closure (LAAC) has emerged as an alternative to oral anticoagulation (OAC) for stroke prevention in patients with atrial fibrillation (AF), particularly among individuals at increased risk of bleeding. We performed an updated systematic review and meta-analysis of randomized controlled trials comparing the efficacy and safety of LAAC versus OAC in AF. PubMed, Embase, and Scopus were searched through May 2026. Risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using a random-effects model, and trial sequential analysis (TSA) was conducted to evaluate the sufficiency of cumulative evidence. Six randomized trials involving 7,004 patients were included. Compared with OAC, LAAC demonstrated similar risks of stroke, systemic embolism, cardiovascular death, all-cause mortality, and transient ischemic attack. LAAC showed a nominally higher risk of ischemic stroke or systemic embolization (RR 1.36, 95% CI 1.04–1.79), although this finding was not robust to sensitivity analysis, with a borderline increase in ischemic stroke. In contrast, LAAC significantly reduced non-procedural clinically relevant bleeding (RR 0.49, 95% CI 0.42-0.58), while major bleeding and hemorrhagic stroke were comparable between groups. TSA confirmed sufficient evidence supporting the reduction in bleeding outcomes but indicated that current evidence remains insufficient to establish definitive conclusions regarding thromboembolic efficacy. Overall, LAAC was not associated with statistically significant differences in several thromboembolic and mortality outcomes compared with OAC, while providing a substantial reduction in non-procedural clinically relevant bleeding. However, the potential signal toward increased ischemic events warrants further investigation in adequately powered randomized trials, particularly against contemporary DOAC-based therapy.