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Volume 344:619-625 March 1, 2001 Number 9 Next

	Full Text PDF Editorial by Rosenberg, R. D. Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

ABSTRACT

Background Venous thromboembolism is a frequent complication of total hip replacement. The pentasaccharide Org31540/SR90107A, a highly selective, indirect inhibitor of activated factor X, is the first of a new class of synthetic antithrombotic agents. To determine the optimal dose for phase 3 studies, we conducted a dose-ranging study in which Org31540/SR90107A was compared with a low-molecular-weight heparin, enoxaparin, in patients undergoing total hip replacement.

Methods In a double-blind study, patients were randomly assigned to postoperative administration of one of five daily doses of Org31540/SR90107A, given once daily, or to 30 mg of enoxaparin, given every 12 hours. Treatment was continued for 10 days or until bilateral venography was performed after a minimum of 5 days.

Results Of 933 patients treated, 593 were eligible for the efficacy analysis. With Org31540/SR90107A a dose effect was observed (P=0.002), with rates of venous thromboembolism of 11.8 percent, 6.7 percent, 1.7 percent, 4.4 percent, and 0 percent for the groups assigned to 0.75 mg, 1.5 mg, 3.0 mg, 6.0 mg, and 8.0 mg of the drug, respectively, as compared with a rate of 9.4 percent in the enoxaparin group. The reduction in the risk of venous thromboembolism was 82 percent for the 3.0-mg Org31540/SR90107A group (P= 0.01) and 29 percent for the 1.5-mg group (P=0.51). Enrollment in the 6.0-mg and 8.0-mg Org31540/SR90107A groups was discontinued because of bleeding complications. Major bleeding occurred 3.5 percent less frequently in the 0.75-mg group (P=0.01) and 3.0 percent less frequently in the 1.5-mg group (P=0.05) than in the enoxaparin group (in which the rate was similar to that in the 3.0-mg group).

Conclusions Org31540/SR90107A, a synthetic pentasaccharide, has the potential to improve significantly the risk–benefit ratio for the prevention of venous thromboembolism, as compared with low-molecular-weight heparin.

Source Information

From McMaster University, Hamilton, Ont., Canada (A.G.G.T.); Flinders Medical Centre, Adelaide, Australia (A.S.G.); and Sanofi–Synthelabo Research, Malvern, Pa. (J.A.H.).

Address reprint requests to Dr. Turpie at Hamilton Health Sciences, General Division, 237 Barton St. E., Hamilton, ON L8L 2X2, Canada, or at turpiea{at}mcmaster.ca.

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