Systematic review and network meta-analysis of the relative efficacy and safety of edoxaban versus other nonvitamin K antagonist oral anticoagulants among patients with nonvalvular atrial fibrillation and CHADS2 score ⩾ 2.
BACKGROUND
The nonvitamin K antagonist oral anticoagulants pivotal clinical trials for stroke prevention in atrial fibrillation have important differences in trial designs and baseline patient characteristics.


OBJECTIVE
We sought to evaluate the relative efficacy and safety of edoxaban versus other nonvitamin K antagonist oral anticoagulants in the management of stroke prevention in atrial fibrillation by adjusting for differences in baseline stroke risk and the length of follow-up among the four phase 3 randomized controlled trials.


METHODS
We conducted a systematic literature review of randomized controlled trials evaluating the nonvitamin K antagonist oral anticoagulants for stroke prevention in atrial fibrillation and performed a network meta-analysis using data from ENGAGE AF-TIMI 48, RE-LY, ROCKET-AF, and ARISTOTLE, with warfarin as a common comparator. To adjust for between-trial differences in CHADS2 score and length of follow-up, annualized event rates among patients with CHADS2 score ⩾ 2 were analyzed using a mixed Poisson's regression model.


RESULTS
Once-daily high-dose edoxaban was associated with significant lower major bleeding episodes compared with once-daily rivaroxaban (risk ratio, 0.76; 95% confidence interval, 0.66-0.89), twice-daily dabigatran 150 mg (risk ratio, 0.78; 95% confidence interval, 0.61-0.84), and twice-daily dabigatran 110 mg (risk ratio, 0.83; 95% confidence interval, 0.71-0.98) and similar bleeding risk compared with twice-daily apixaban (risk ratio, 1.08; 95% confidence interval, 0.91-1.28). Risk of stroke and systemic embolism was similar for the high-dose edoxaban and other nonvitamin K antagonist oral anticoagulant regimens. The low-dose edoxaban regimen was associated with a significant lower risk of major bleeding than other nonvitamin K antagonist oral anticoagulants and a significant higher risk of stroke and systemic embolism compared with apixaban and dabigatran 150 mg.


CONCLUSIONS
Among patients with atrial fibrillation and CHADS2 score ⩾ 2, the high-dose edoxaban regimen may offer similar efficacy to the other nonvitamin K antagonist oral anticoagulants but with a significant major bleeding benefit over rivaroxaban and dabigatran.
RTI Health Solutions, Durham, NC, USA.
Maria M
MM
Fernandez
RTI Health Solutions, Durham, NC, USA.
Jianmin
J
Wang
Daiichi Sankyo, Inc., Parsippany, NJ, USA.
Xin
X
Ye
Daiichi Sankyo, Inc., Parsippany, NJ, USA.
Winghan Jacqueline
WJ
Kwong
RTI Health Solutions, Durham, NC, USA.
Bintu
B
Sherif
RTI Health Solutions, Durham, NC, USA.
Susan
S
Hogue
RTI Health Solutions, Durham, NC, USA.
Beth
B
Sherrill
Cardiovascular; anticoagulants; atrial fibrillation; meta-analysis