Oral ximelagatran at 36 mg twice daily was superior to warfarin for the prevention of venous thromboembolism and death after total knee replacement (20.3% vs. 27.6%; P=0.003).
RCT (n=1,851)
double-blind
randomized
Does oral ximelagatran reduce the composite of venous thromboembolism and death compared to warfarin in patients after total knee replacement?
Oral ximelagatran 36 mg twice daily is superior to warfarin for preventing venous thromboembolism after total knee replacement without increasing bleeding risk.
Absolute Event Rate: 20.3% vs 27.6%
p-value: p=0.003
BACKGROUND: In a previous study of the prevention of venous thromboembolism after total knee replacement, the efficacy of ximelagatran, an oral direct thrombin inhibitor that does not require monitoring of coagulation or dose adjustment, was found to be similar to that of warfarin at a dose of 24 mg of ximelagatran twice daily. The purpose of the present study was to determine whether a higher dose of ximelagatran is superior to warfarin. METHODS: This randomized, double-blind trial compared a regimen of 7 to 12 days of oral ximelagatran, at a dose of 24 or 36 mg twice daily, starting the morning after surgery, with warfarin therapy started the evening of the day of surgery. The composite end point of venous thromboembolism and death from all causes and the incidence of bleeding were the primary outcome measures. RESULTS: Among the 1851 patients in the efficacy analysis, oral ximelagatran at a dose of 36 mg twice daily was superior to warfarin with respect to the primary composite end point of venous thromboembolism and death from all causes (20.3 percent vs. 27.6 percent; P=0.003). There were no significant differences between these two groups with respect to major bleeding (incidence, 0.8 percent and 0.7 percent, respectively), perioperative indicators of bleeding, wound characteristics, or the composite secondary end point of proximal deep-vein thrombosis, pulmonary embolism, and death (2.7 percent vs. 4.1 percent; P=0.17). CONCLUSIONS: The efficacy of oral ximelagatran, administered starting the morning after total knee replacement, was superior to that of warfarin for prevention of venous thromboembolism. Rates of hemorrhagic complications with the two drugs were similar.
Francis et al. (Thu,) führten eine RCT zur venösen Thromboembolie nach totaler Kniegelenkersatzoperation (n=1.851) durch. Ximelagatran vs. Warfarin wurde anhand eines zusammengesetzten Endpunkts von venöser Thromboembolie und Tod aus allen Ursachen bewertet (p=0.003). Orales Ximelagatran mit 36 mg zweimal täglich war gegenüber Warfarin zur Prävention von venöser Thromboembolie und Tod nach totalem Kniegelenkersatz überlegen (20.3 % vs. 27.6 %; P=0.003).