Direct Oral Anticoagulants for Stroke Prevention in Atrial Fibrillation: A Global Synthesis of Randomized Evidence through Network Meta-Analysis

Abstract Background and Objectives Direct oral anticoagulants (DOACs) have become preferred alternatives to vitamin K antagonists (VKAs) for stroke prevention in both valvular (VAF) and non-valvular atrial fibrillation (NVAF). However, comparative evidence on the relative efficacy and safety of different DOACs remains limited. This network meta-analysis aimed to systematically assess and compare the efficacy and safety of various DOACs versus VKAs in preventing stroke and related outcomes among patients with AF. Methods A comprehensive literature search of PubMed, EMbase, and the Cochrane Library was conducted for randomized controlled trials (RCTs) published up to October 31, 2024. A Bayesian network meta-analysis was performed using odds ratios (ORs) with corresponding 95% credible intervals (CrIs). Results A total of 43 RCTs were included, comprising 30 on VAF and 13 on NVAF. Compared to VKA, apixaban (OR = 0.81; 95% CrI: 0.73 to 0.91), dabigatran (OR = 0.77; 95% CrI: 0.68 to 0.87), and rivaroxaban (OR = 0.87; 95% CrI: 0.79 to 0.96) were significantly associated with reduced risk of IS/SE, while edoxaban showed a non-significant effect. All DOACs were significantly superior to VKA in reducing the risk of HS. For major bleeding, apixaban (OR = 0.69; 95% CrI: 0.55 to 0.88) showed a significant advantage over VKA, while dabigatran and rivaroxaban were associated with non-significant increases. In terms of all-cause mortality, apixaban significantly reduced risk in NVAF (OR = 0.88; 95% CrI: 0.82 to 0.96), whereas dabigatran, edoxaban, and rivaroxaban showed non-significant associations. In VAF, neither dabigatran nor rivaroxaban demonstrated a significant impact on mortality. Conclusion This network meta-analysis suggests that apixaban and dabigatran are associated with significantly better outcomes in terms of reducing ischemic and hemorrhagic events, major bleeding, and mortality compared to VKAs, particularly in NVAF patients. Edoxaban and rivaroxaban showed favourable but generally non-significant associations. These findings support the use of apixaban and dabigatran for stroke prevention in patients with AF.