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Previous Volume 349:1713-1721 October 30, 2003 Number 18 Next

	Full Text PDF PDA Full Text PowerPoint Slide Set 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 For many patients with venous thromboembolism, secondary prevention with vitamin K antagonists is not extended beyond six months, since the risk of recurrence may be outweighed by the risk of major bleeding.

Methods In a double-blind, multicenter trial, we randomly assigned 1233 patients with venous thromboembolism who had undergone six months of anticoagulant therapy to extended secondary prevention with the oral direct thrombin inhibitor ximelagatran (24 mg) or placebo, taken twice daily, for 18 months without monitoring of coagulation. At base line, bilateral ultrasonography of the legs and perfusion lung scanning were performed.

Results Data from 612 patients in the ximelagatran group and 611 in the placebo group were analyzed. The occurrence of the primary end point, symptomatic recurrent venous thromboembolism, was confirmed in 12 patients assigned to ximelagatran and 71 patients assigned to placebo (hazard ratio, 0.16; 95 percent confidence interval, 0.09 to 0.30; P<0.001). Death from any cause occurred in 6 patients in the ximelagatran group and 7 patients in the placebo group, and bleeding occurred in 134 patients and 111 patients, respectively (hazard ratio, 1.19; 95 percent confidence interval, 0.93 to 1.53; P=0.17). The incidence of major hemorrhage was low (six events in the ximelagatran group and five in the placebo group), and none of these hemorrhages were fatal. The cumulative risk of a transient elevation of the alanine aminotransferase level to more than three times the upper limit of normal was 6.4 percent in the ximelagatran group, as compared with 1.2 percent in the placebo group (P<0.001).

Conclusions Oral ximelagatran was superior to placebo for the extended prevention of venous thromboembolism. There was no significant increase in the frequency of bleeding complications, but there was an increase in the number of patients with a transient elevation in the alanine aminotransferase level.

Source Information

From the Coagulation Unit, Department of Medicine, Karolinska Hospital, Stockholm (S.S.); AstraZeneca Research and Development Mölndal, Mölndal (K.W., T.L., S.B.C.); the Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska University Hospital, Gothenburg (K.W.); and the Department of Medicine, Sahlgrenska University Hospital–Östra, Gothenburg (H.E.) — all in Sweden.

Address reprint requests to Dr. Schulman at the Coagulation Unit, Karolinska Hospital, S-171 76 Stockholm, Sweden, or at sam.schulman{at}ks.se.

Full Text of this Article

Related Letters:

Ximelagatran for Secondary Prevention of Venous Thromboembolism
Vaknansky A., Kupfer Y., Tessler S., Böger C., Schroll S., Holmer S., Schulman S., Eriksson H.
Extract | Full Text | PDF  
N Engl J Med 2004; 350:618-619, Feb 5, 2004. Correspondence

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