Comparison of low-intensity warfarin therapy with conventional-intensity warfarin therapy for long-term prevention of recurrent venous thromboembolism

Clive Kearon, Jeffrey S. Ginsberg, Michael J. Kovacs, David R. Anderson, Philip Wells, Jim A. Julian, Betsy MacKinnon, Jeffrey I. Weitz, Mark A. Crowther, Sean Dolan, Alexander G. Turpie, William Geerts, Susan Solymoss, Paul Van Nguyen, Christine Demers, Susan R. Kahn, Jeannine Kassis, Marc Rodger, Julie Hambleton, Michael Gent

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BACKGROUND: Warfarin is very effective in preventing recurrent venous thromboembolism but is also associated with a substantial risk of bleeding. After three months of conventional warfarin therapy, a lower dose of anticoagulant medication may result in less bleeding and still prevent recurrent venous thromboembolism. METHODS: We conducted a randomized, double-blind study, in which 738 patients who had completed three or more months of warfarin therapy for unprovoked venous thromboembolism were randomly assigned to continue warfarin therapy with a target international normalized ratio (INR) of 2.0 to 3.0 (conventional intensity) or a target INR of 1.5 to 1. 9 (low intensity). Patients were followed for an average of 2.4 years. RESULTS: Of 369 patients assigned to low-intensity therapy, 16 had recurrent venous thromboembolism (1.9 per 100 person-years), as compared with 6 of 369 assigned to conventional-intensity therapy (0.7 per 100 person-years; hazard ratio, 2.8; 95 percent confidence interval, 1.1 to 7.0). A major bleeding episode occurred in nine patients assigned to low-intensity therapy (1.1 events per 100 person-years) and eight patients assigned to conventional-intensity therapy (0. 9 event per 100 person-years; hazard ratio, 1.2; 95 percent confidence interval, 0.4 to 3.0). There was no significant difference in the frequency of overall bleeding between the two groups (hazard ratio, 1.3; 95 percent confidence interval, 0.8 to 2.1). CONCLUSIONS: Conventional-intensity warfarin therapy is more effective than low-intensity warfarin therapy for the long-term prevention of recurrent venous thromboembolism. The low-intensity warfarin regimen does not reduce the risk of clinically important bleeding.

Original languageEnglish
Pages (from-to)631-639
Number of pages9
JournalNew England Journal of Medicine
Issue number7
StatePublished - 14 Aug 2003
Externally publishedYes


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