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Oral anticoagulation (OAC) and left atrial appendage closure (LAAC) are stroke prevention strategies for patients with atrial fibrillation.

To compare stroke and bleeding outcomes from a meta-analysis of randomized controlled trials comparing LAAC to OAC.

The primary outcome was stroke or systemic embolism (stroke/SE). Secondary outcomes included ischemic stroke, hemorrhagic stroke, major bleeding (MB), clinically significant bleeding (MB + clinically relevant nonmajor bleeding), non-procedure related clinically-significant bleeding, and cardiovascular or all-cause mortality.

Seven randomized controlled trials met inclusion criteria (n = 7,353 patients; CHA₂DS₂-VASc score: 3.9; mean follow-up: 37.6 months), including 294 stroke/SE events. LAAC was similar to OAC for preventing stroke/SE (risk ratio [RR]: 1.10, 95% CI: 0.82-1.48). Clinically significant bleeding (RR: 0.60, 95% CI: 0.36-0.98) and non-procedure-related clinically significant bleeding (RR: 0.50, 95% CI: 0.39-0.64) were less frequent after LAAC. No statistically significant differences were observed for ischemic stroke, hemorrhagic stroke, MB, cardiovascular mortality, or all-cause mortality. The annualized incidence rate difference of stroke with LAAC did not increase with higher CHA₂DS₂-VASc scores and did not exceed 0.37%/year in any nonwarfarin-OAC comparative trial. In postablation patients, LAAC showed similar stroke/SE rates (RR: 0.92, 95% CI: 0.53-1.60; P-interaction = 0.76) and less nonprocedural clinically significant bleeding (RR: 0.51, 95% CI: 0.42-0.62; P-interaction = 0.56).

LAAC prevents stroke/SE at rates not significantly different from OAC while reducing clinically significant bleeding, with possibly a more favorable benefit in postablation patients. In the full cohort, the numerically higher ischemic stroke rate was not statistically significant, and small in absolute terms. These findings support LAAC based on individualized, patient-centered decision-making, balancing stroke and bleeding risks.