Edoxaban ( Savaysa ) is a direct oral factor Xa inhibitor with proven antithrombotic effects. The long-term efficacy and safety of Edoxaban as compared with Warfarin ( Coumadin ) in patients with atrial fibrillation is not known.
ENGAGE AF-TIMI 48 Investigators conducted a randomized, double-blind, double-dummy trial comparing two once-daily regimens of Edoxaban with Warfarin in 21,105 patients with moderate-to-high-risk atrial fibrillation ( median follow-up, 2.8 years ).
The primary efficacy end point was stroke or systemic embolism. Each Edoxaban regimen was tested for noninferiority to Warfarin during the treatment period.
The principal safety end point was major bleeding.
The annualized rate of the primary end point during treatment was 1.50% with Warfarin ( median time in the therapeutic range, 68.4% ), as compared with 1.18% with high-dose Edoxaban ( hazard ratio, HR=0.79; P less than 0.001 for noninferiority ) and 1.61% with low-dose Edoxaban ( HR=1.07; P=0.005 for noninferiority ).
In the intention-to-treat analysis, there was a trend favoring high-dose Edoxaban versus Warfarin ( HR=0.87; P=0.08 ) and an unfavorable trend with low-dose Edoxaban versus Warfarin ( HR=1.13; P=0.10 ).
The annualized rate of major bleeding was 3.43% with Warfarin versus 2.75% with high-dose Edoxaban ( HR=0.80; P less than 0.001 ) and 1.61% with low-dose Edoxaban ( HR=0.47; P less than 0.001 ).
The corresponding annualized rates of death from cardiovascular causes were 3.17% versus 2.74% ( HR=0.86; P=0.01 ), and 2.71% ( HR=0.85; P=0.008 ), and the corresponding rates of the key secondary end point ( a composite of stroke, systemic embolism, or death from cardiovascular causes ) were 4.43% versus 3.85% ( HR=0.87; P=0.005 ), and 4.23% ( HR=0.95; P=0.32 ).
In conclusion, both once-daily regimens of Edoxaban were noninferior to Warfarin with respect to the prevention of stroke or systemic embolism and were associated with significantly lower rates of bleeding and death from cardiovascular causes. ( Xagena )
Giugliano RP et al, N Engl J Med 2013; 369:2093-2104