Background: Notable differences in patient characteristics exist among the phase 3 trials studying non-VKA oral anticoagulants (NOACs) for stroke prevention in atrial fibrillation. This study compared the efficacy and safety of edoxaban versus other NOACs after adjustment of baseline patient characteristics for key prognostic factors.
Methods: A network meta-analysis using data from ENGAGE-AF TIMI-48, RELY, ROCKET-AF and ARISTOTLE with warfarin as a common comparator was performed. To adjust for differences in CHADS₂ score and length of follow-up across the trials, annualized event rates among patients with CHADS₂ score ≥ 2 were analyzed using mixed Poisson regression.
Results: While efficacy for the composite endpoint of stroke and systemic embolism (SEE) was similar for high dose edoxaban QD compared to other NOAC regimens, high dose edoxaban significantly reduced major bleeding risk by 24%, 28%, and 17% compared to rivaroxaban QD, and dabigatran 150 mg BID, and dabigatran 110 mg BID, respectively. Major bleeding rates were similar between high dose edoxaban QD and apixaban BID. Low dose edoxaban QD had similar efficacy and reduced bleeding compared to rivaroxaban and dabigatran 110 mg, and had higher rates of stroke/SEE and reduced bleeding rates compared to apixaban and dabigatran 150 mg.
Conclusion: In this adjusted indirect comparison, high-dose edoxaban offered similar efficacy to the other NOAC regimens but with a significant major bleeding benefit over rivaroxaban and dabigatran.
