Left Atrial Appendage Closure, Direct Oral Anticoagulants or Warfarin in Atrial Fibrillation: A Systematic Review and Network Meta-analysis of Randomized Clinical Trials

BackgroundLeft 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. MethodsWe 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. ResultsTen 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{middle dot}43, 95% CI 0{middle dot}34-0{middle dot}54) and LAAC (OR 0{middle dot}34, 95% CI 0{middle dot}18-0{middle dot}63) reduced the primary safety outcome of HS, with no significant difference between them (OR 0{middle dot}79, 95% CI 0{middle dot}44-1{middle dot}3). For NACE, both DOACs (OR 0{middle dot}87, 95% CI 0{middle dot}83-0{middle dot}91) and LAAC (OR 0{middle dot}85, 95% CI 0{middle dot}73-0{middle dot}99) were superior to warfarin, with similar performance between them (OR 0{middle dot}98, 95% CI 0{middle dot}84-1{middle dot}13). For MCRB, DOACs were superior to warfarin (OR 0{middle dot}79, 95% CI 0{middle dot}63-0{middle dot}99), while LAAC showed a non-significant trend towards benefit. ConclusionIn 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. FundingNone.