LAAC and DOACs match warfarin for stroke prevention in AF patients

Background: Left atrial appendage closure (LAAC) and direct oral anticoagulants (DOACs) have emerged as alternatives to warfarin for stroke prevention in atrial fibrillation (AF). However, recent trials have shown variable results igniting the debate on this topic. Methods: We performed a systematic review and network meta-analysis (NMA) of RCTs comparing LAAC, DOACs, and warfarin in patients with AF. The primary efficacy outcome was ischemic stroke or systemic embolism (IS/SE) and the primary bleeding outcome was hemorrhagic stroke (HS). Secondary outcomes included net adverse clinical events (NACE) and major or clinically relevant bleeding (MCRB). Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using a random-effects model. Results: Ten RCTs (LAAC: 6 trials; DOAC: 8 trials; warfarin: 6 trials) enrolling 78,594 patients fulfilled the inclusion criteria. There were no significant differences for the primary efficacy outcome of IS/SE among the 3 strategies. However, when compared with warfarin, both DOACs (OR 0.43, 95% CI 0.34-0.54) and LAAC (OR 0.34, 95% CI 0.18-0.63) reduced the primary safety outcome of HS, with no significant difference between them (OR 0.79, 95% CI 0.44-1.3). For NACE, both DOACs (OR 0.87, 95% CI 0.83-0.91) and LAAC (OR 0.85, 95% CI 0.73-0.99) were superior to warfarin, with similar performance between them (OR 0.98, 95% CI 0.84-1.13). For MCRB, DOACs were superior to warfarin (OR 0.79, 95% CI 0.63-0.99), while LAAC showed a non-significant trend towards benefit. Conclusion: In this meta-analysis of RCTs with data from over 78,000 patients, LAAC and DOACs significantly reduced NACE driven by lower hemorrhagic stroke and provided equivalent IS/SE protection compared with warfarin, making LAAC a potential viable alternative to oral anticoagulation in appropriately selected AF patients.