BACKGROUND:Percutaneous left atrial appendage occlusion (LAAO) is an alternative strategy for stroke prevention in patients with nonvalvular atrial fibrillation (AF) with contraindications to long-term oral anticoagulation therapy. However, evidence comparing the long-term outcomes of LAAO with those of direct oral anticoagulants (DOAC) remains limited. METHODS:A systematic search was conducted across PubMed, Scopus, and the Cochrane databases through April 2026. Co-primary outcomes were major adverse cardiovascular and cerebrovascular events (MACCE; composite of cardiac death, stroke, or systemic embolism) and net adverse clinical events (NACE; composite of MACCE and non-procedure-related bleeding). Secondary endpoints included individual components of co-primary endpoints, ischemic and hemorrhagic stroke, all-cause death, major or clinically significant bleeding (procedure + non-procedure related), and stroke or systemic embolism. The random-effects model was used to generate risk ratios (RRs) and 95% CIs. RESULTS:Four randomized controlled trials comprising 5890 AF patients and a median follow-up of 3 years were included. There was no significant difference between LAAO and DOAC therapy in the risk of MACCE (RR 1.17; 95%CI 0.96-1.41; I2 = 0%) or NACE (RR 0.89; 95%CI 0.65-1.24; I2 = 85%). Both LAAO and DOAC therapy were similar in risk of cardiac death, stroke, systemic embolism, hemorrhagic stroke, ischemic stroke, all-cause mortality, stroke or systemic embolism, and pericardial effusion. LAAO was associated with a lower risk of non-procedure-related bleeding (RR 0.60; 95%CI 0.47-0.76; I2 = 59%). CONCLUSION:LAAO demonstrated efficacy comparable to DOAC therapy in reducing the risk of MACCE, NACE, and ischemic events, while significantly reducing the risk of non-procedure-related bleeding. Our findings support a tailored approach to stroke prevention in AF, wherein LAAO serves as an effective alternative for patients with contraindications to DOAC therapy.
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