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Low-Intensity Warfarin Reduces Risk for Recurrent Idiopathic DVT or PE

Warfarin decreased risk for venous thrombosis without increasing risk for major bleeding episodes.

Patients with idiopathic deep-vein thrombosis (DVT) or pulmonary embolism (PE) are at high risk for recurrence after completing the usual 3- to 12-month course of warfarin. But, if full-dose warfarin is continued indefinitely, cumulative risk for serious bleeding becomes substantial. These researchers sought to determine whether low-intensity warfarin (provided by the manufacturer at no cost) prevents recurrent venous thromboembolism without causing excessive bleeding.

A total of 508 patients with idiopathic DVT or PE were enrolled; median duration of full-dose warfarin anticoagulation (target INR, 2.0-3.0) before enrollment was 6 months. The patients were randomized to receive low-intensity warfarin (target INR, 1.5-2.0) or placebo indefinitely. After an average follow-up of 2.1 years, the study was terminated: Venous thromboembolism recurred in 14 of 255 warfarin recipients but in 37 of 253 placebo recipients -- a significant difference. Although minor bleeding episodes were more common with warfarin than with placebo, there was no significant difference in the number of major bleeding episodes (5 and 2 patients, respectively). There were 4 deaths in the warfarin group and 8 in the placebo group. The benefit with warfarin was similar among patients with inherited thrombophilias (i.e., factor V Leiden or prothrombin mutation) and those without identified thrombophilias.

Comment: Results from this study strongly suggest that long-term, low-intensity warfarin (INR, 1.5-2.0) safely reduces risk for recurrent idiopathic DVT or PE. However, an editorialist notes that in another study, as yet published only in abstract form, long-term, standard-intensity warfarin was more effective than low-intensity warfarin, with no difference in bleeding complications. Until these findings are reconciled, it seems reasonable for clinicians to prescribe long-term, low-intensity warfarin for patients similar to those in this trial. At the time of publication, these articles were presented as early releases at http://content.nejm.org/cgi/reprint/NEJMoa035029v1.pdf and http://content.nejm.org/cgi/reprint/NEJMe030018v1.pdf free of charge.

— Allan S. Brett, MD

Published in Journal Watch General Medicine April 4, 2003

Citation(s):

Ridker PM et al. Long-term, low-intensity warfarin therapy for the prevention of recurrent venous thromboembolism. N Engl J Med 2003 Apr 10; 348:1425-34.

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Schafer AI. Warfarin for venous thromboembolism -- Walking the dosing tightrope. N Engl J Med 2003 Apr 10; 348:1478-80.

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