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Previous Volume 349:1703-1712 October 30, 2003 Number 18 Next

	Full Text PDF PDA Full Text PowerPoint Slide Set Supplementary Material Editorial by Shapiro, S. S. Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear PubMed Citation

ABSTRACT

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.

Source Information

From the Department of Medicine, University of Rochester, Rochester, N.Y. (C.W.F.); the Department of Clinical Development, AstraZeneca, Wilmington, Del. (S.D.B., G.R.P., A.W.R., J.M.); the Department of Medicine, University of Oklahoma, Oklahoma City (P.C.C.); the Department of Orthopedic Surgery, University of California at Los Angeles, Los Angeles (J.R.L.); the Department of Medicine, McMaster University, Hamilton, Ont., Canada (J.S.G.); the Department of Orthopedic Surgery, University of California at Irvine, Irvine (G.P.); and the Department of Orthopaedic Surgery, Scripps Clinic, La Jolla, Calif. (C.W.C.).

Address reprint requests to Dr. Francis at the University of Rochester Medical Center, 610 Elmwood Ave., Box 610, Rochester, NY 14642, or at charles_francis{at}urmc.rochester.edu.

Full Text of this Article

Related Letters:

Ximelagatran versus Warfarin after Total Knee Replacement
Banarer S., Schillaci G., Pasqualini L., Mannarino E., Nishiguchi M., Takamura N., Aoyagi K., Francis C. W., Berkowitz S. D., Colwell C. W. Jr.
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N Engl J Med 2004; 350:616-617, Feb 5, 2004. Correspondence

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