BACKGROUND: Oral anticoagulation (OAC) has been considered the standard of care for stroke prophylaxis for patients with nonvalvular atrial fibrillation; however, many individuals are unable or unwilling to take long-term OAC. The safety and efficacy of percutaneous left atrial appendage closure (LAAC) have been controversial, and new trial data have recently emerged. We therefore sought to perform an updated meta-analysis of randomized clinical trials (RCTs) comparing OAC to percutaneous LAAC, focusing on individual clinical endpoints. METHODS: We performed a systematic search of the MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials from January 2000 through December 2021 for all RCTs comparing percutaneous LAAC to OAC in patients with nonvalvular atrial fibrillation. Fixed and random effects meta-analyses of hazard ratios (HRs) were performed using the longest follow-up duration available by intention-to-treat. The prespecified primary endpoint was all-cause mortality. RESULTS: Three RCTs enrolling 1516 patients were identified. The weighted mean follow-up was 54.7 months. LAAC was associated with a reduced risk of all-cause mortality (HR 0.76; 95% confidence interval [CI], 0.59-0.96; p = 0.023), hemorrhagic stroke (HR 0.24; 95% CI, 0.09-0.61; p = 0.003), and major nonprocedural bleeding (HR 0.52; 95% CI, 0.37-0.74; p < 0.001). There was no significant difference between LAAC and OAC for any other endpoints. CONCLUSIONS: The available evidence from RCTs suggests LAAC therapy is associated with reduced long-term risk of death compared with OAC. This may be driven by reductions in hemorrhagic stroke and major nonprocedural bleeding. There were no significant differences in the risk of all stroke. Further large-scale clinical trials are needed to validate these findings.

Cardiocenter 3rd Faculty of Medicine Charles University Prague and University Hospital Kralovske Vinohrady Prague Czech Republic

Cardiovascular Research Foundation New York New York USA

Department of Cardiovascular Medicine Mayo Clinic Rochester Minnesota USA

Division of Cardiology Department of Medicine NewYork Presbyterian Hospital and the Columbia University Irving Medical Center New York New York USA

National Heart and Lung Institute Imperial College London London UK

Smidt Heart Institute Cedars Sinai Medical Center Los Angeles California USA

The Helmsley Electrophysiology Center Icahn School of Medicine at Mount Sinai New York New York USA

The Zena and Michael A Wiener Cardiovascular Institute Icahn School of Medicine at Mount Sinai New York New York USA

Yale School of Medicine Yale University New Haven Connecticut USA

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