AIM: Atrial fibrillation is the most commonly sustained cardiac arrhythmia, increasing the risk of stroke and systemic embolic events. This systematic review and network meta-analysis (NMA) aimed to compare real-world evidence (RWE) on the effectiveness and safety of edoxaban with other direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) in patients with non-valvular atrial fibrillation (NVAF) in Europe.

MATERIALS & METHODS: Searches from January 2013 to December 2022 identified comparative observational studies assessing effectiveness/safety outcomes in patients with NVAF. Bayesian NMA estimated comparative effectiveness/safety of edoxaban with other DOACs and VKAs.

RESULTS: The review identified 57 studies analyzing data from 24 unique databases; 33 studies were included in the base-case analyses. DOACs showed benefit over VKAs for most outcomes, of which major bleeding and all-cause mortality were most commonly reported. Edoxaban demonstrated a comparable effectiveness/safety profile to other DOACs and significantly reduced risk of major bleeding (hazard ratio [95% credible interval]: 0.67 [0.54, 0.84]) and intracranial hemorrhage (0.69 [0.51, 0.94]) versus rivaroxaban.

CONCLUSION: This NMA provides valuable insights into the real-world effectiveness and safety of DOACs and VKAs in Europe, supporting clinical decision-making and adding to the existing evidence base from clinical trials.