BACKGROUND: Left atrial appendage occlusion (LAAO) is an alternative to chronic oral anticoagulation (OAT) for stroke prevention in nonvalvular atrial fibrillation (NVAF) patients with contraindications to OAT. Postprocedure antithrombotic therapy (ATT) is essential to reduce the risk of device-related thrombosis (DRT), but the optimal regimen remains uncertain. AIMS: This study aims to compare the safety and efficacy of low-dose direct oral anticoagulants (DOACs) versus dual antiplatelet therapy (DAPT) following LAAO. METHODS: A comprehensive search of PubMed, Scopus, Cochrane, and Web of Science was conducted in August 2024. Studies comparing low-dose DOACs and DAPT post-LAAO were included. The primary outcomes were a composite efficacy endpoint (DRT, strokes, and systemic embolism [SE]) and major bleeding events as the safety endpoint. Secondary outcomes included all bleeding events, all-cause mortality, and a composite of efficacy and safety endpoints. RESULTS: Four studies with 727 patients were included. Low-dose DOACs were associated with lower rates of the primary composite efficacy endpoint compared to DAPT (OR = 0.36
95% CI [0.16, 0.85], p = 0.01). No significant difference in major bleeding events was observed (OR = 0.36
95% CI [0.11, 1.18]
p = 0.091
I² = 0%). Compared to DAPT, low-dose DOACs were also associated with lower rates of DRT events (OR = 0.36
95% CI [0.16, 0.79], p = 0.011). CONCLUSION: Low-dose DOACs effectively reduce thromboembolic events post-LAAO without increasing bleeding risk. These findings support their use as a viable ATT option, but larger trials are needed to confirm optimal regimens.