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Long-Term, Low-Intensity Warfarin Prevents VTE Recurrence

Specific guidance for long-term secondary prevention of venous thromboembolism

Oral anticoagulation therapy is recommended for at least 3 months in patients with venous thromboembolism (VTE) and reversible risk factors, for at least 6 months in patients with a first idiopathic-VTE episode, and for at least 12 months in patients with recurrent idiopathic VTE or a long-term risk factor. What intensity of anticoagulation represents the best strategy for long-term prophylaxis against recurrent VTE?

In this multicenter, NIH-sponsored trial, patients with documented idiopathic VTE (minimum age, 30) who had completed at least 3 months of uninterrupted warfarin therapy (median duration, 6.5 months) were randomized to a long-term strategy of either low-intensity warfarin (target INR, 1.5-2.0) or matching placebo. Randomization started after a 28-day, open-label, run-in phase.

During follow-up (mean, 2.1 years; maximum, 4.3), VTE recurred in 14 of 255 low-intensity warfarin recipients and in 37 of 253 placebo recipients (2.6 vs. 7.2 per 100 person-years, P<0.001; 64% risk reduction), prompting the Data Safety and Monitoring Board to stop the trial early. Results were similar by age, sex, and inherited thrombophilia (e.g., factor V Leiden) status.

The warfarin and placebo groups experienced similar numbers of major-bleeding events (5 and 2, respectively) and deaths (4 and 8, respectively). Compared with placebo, low-intensity warfarin was associated with a 48% lower risk for the composite endpoint of recurrent VTE, major bleeding, or death.

Comment: An editorialist notes that VTE now is recognized as a chronic disease and, at least in part, as a systemic disorder characterized in most affected patients by an underlying hereditary hypercoagulable state. Therefore, a long-term secondary-prevention strategy is in order. This study suggests that a reasonable strategy, for now, is low-intensity warfarin therapy in patients who require more than 3 months of anticoagulation therapy after an initial VTE episode. A comparison of different INR-target strategies in future studies would be helpful.

— Joel M. Gore, MD

Published in Journal Watch Cardiology April 18, 2003

Citation(s):

Ridker PM et al. for the PREVENT Investigators. 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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• Medline abstract (Free)

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

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• Medline abstract (Free)