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Title: Conventional-Intensity Superior to Low-Intensity Warfarin in Preventing Recurring Venous Thromboembolism

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N Engl J Med 2003;349:631-9
08/13/2003 05:00:00 PM
By Joene Hendry

A conventional-intensity warfarin therapy is more effective than low-intensity warfarin in the prevention of recurring venous thromboembolism among patients who have had unprovoked venous thromboembolism. Conventional dosage reduces the risk of recurrent venous thromboembolism by about two-thirds in this patient population. "Long-term conventional-intensity warfarin therapy is very effective at preventing recurrent thrombosis and is associated with a low frequency of bleeding," writes Clive Kearon MB, PhD, of McMaster University, Hamilton, Ontario, Canada and colleagues. They conducted a randomised, double- blind study of conventional and low-dose warfarin in 738 patients who had already completed 3 or more months of warfarin therapy for unprovoked venous thromboembolism. The low-intensity warfarin group, 369 patients, was assigned to therapy adjusted to achieve a target international normalized ratio (INR) of 1.5 to 1.9, while the 369 patients in the conventional-intensity group received warfarin therapy adjusted to an INR target of 2.0 to 3.0. Average follow up was 2.4 years. Recurrent venous thromboembolism occurred in 16 patients in the low-intensity group including 13 cases of deep venous thrombosis, 2 nonfatal pulmonary embolisms, and 1 fatal event suspected to have been a pulmonary embolism. The mean INR among patients in the low-intensity group was 1.8. Among the conventional-intensity group 6 episodes of recurrent venous thromboembolism occurred, including 4 cases of deep venous thrombosis and 2 fatal events categorised as pulmonary embolisms. The mean INR among this group was 2.4. The investigators report no significant difference in the frequency of bleeding episodes between treatment groups with major bleeding episodes occurring in 9 of the low- intensity group and 8 in the conventional-therapy group. Dr. Kearon and colleagues conclude, "the intensity of anticoagulant therapy for patients who have had unprovoked venous thromboembolism should not be reduced after the first three months of treatment, since such reduction increases the risk of recurrent thrombosis and there is no evidence that it reduces the risk of bleeding."

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