OBJECTIVES: Vitamin K antagonists (VKAs) such as warfarin, and direct oral anticoagulants (DOACs) such as apixaban, dabigatran, edoxaban, and rivaroxaban are routinely prescribed for patients with non-valvular atrial fibrillation (NVAF) to reduce the risk of ischemic stroke and systemic embolism (SE). Meta-analyses of randomized controlled trials demonstrate that DOACs are at least equivalent to VKAs in terms of efficacy and safety, however, whether analyses of real-world evidence (RWE) conclude similar outcomes is unknown. This study aimed to compare the effectiveness and safety of DOACs with VKAs in patients with NVAF based on RWE.

METHODS: A systematic literature review (SLR) was conducted to identify prospective and retrospective real-world studies in adults with NVAF receiving DOACs or VKAs. A Bayesian network meta-analysis (NMA) was performed and fixed and random effects models were used to assess the effectiveness and safety of each DOAC compared to VKAs for stroke/SE (including ischemic stroke), major bleeding (including intracranial hemorrhage (ICH)), and all-cause mortality outcomes.

RESULTS: Literature searches conducted in October 2021 identified 79 studies for inclusion in the NMA. All DOACs, except edoxaban, were associated with lower risk of stroke/SE compared to VKAs. Apixaban and edoxaban were associated with lower risk of ischemic stroke and only apixaban was associated with lower risk of SE. Risks of major bleed were lower for all DOACs except rivaroxaban; all DOACs were associated with lower risk of ICH compared with VKAs. All DOACs, except edoxaban, were associated with lower risk of all-cause mortality compared to VKAs.

CONCLUSIONS: In line with evidence from similar NMAs of randomized controlled trials, the results of this NMA of RWE demonstrate that all DOACs are at least as effective as VKAs in terms of both effectiveness and safety. Apixaban was the only DOAC associated with lower risk across all outcomes compared to VKAs.