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Low-Intensity Warfarin Is Too Low

An INR target of 2.0-3.0 remains appropriate for secondary prevention of venous thromboembolism.

In a recent multicenter, randomized trial that enrolled patients with documented idiopathic venous thromboembolism (VTE) who had completed at least 3 months of uninterrupted warfarin therapy, a long-term strategy of low-intensity warfarin (target INR, 1.5-2.0) was significantly more effective than placebo for preventing VTE recurrence (Journal Watch Cardiology Apr 18 2003).

In a new multicenter study, researchers compared different INR-target strategies directly. They randomized 738 patients with unprovoked venous thromboembolism (65% with deep-vein thrombosis only, 35% with pulmonary embolism) who had received at least 3 months of conventional-intensity warfarin to continued therapy at either low intensity (target INR, 1.5-1.9; mean, 1.8) or conventional intensity (target INR, 2.0-3.0; mean, 2.4). Mean follow-up was 2.4 years.

Compared with the conventional-intensity group, the low-intensity group had a significantly higher rate of VTE recurrence (1.9% vs. 0.7%), a marginally higher mortality rate (1.9% vs. 0.9%), and similar rates of major bleeding (1.1% vs. 0.9%) and any bleeding (4.9% vs. 3.7%). Factor V Leiden did not predict VTE recurrence.

Comment: The authors conclude that the intensity of warfarin therapy should not be reduced after the initial 3 months of treatment in patients who have had unprovoked venous thromboembolism. The editorialists declare that the debate about treatment intensity for VTE is now settled and that the remaining unresolved issue is the optimal duration of therapy. No one has identified any subgroups for whom conventional-intensity treatment is unnecessary, so an INR target of 2.0-3.0 remains the appropriate one for secondary prevention of VTE.

— Harlan M. Krumholz, MD, SM

Published in Journal Watch Cardiology September 12, 2003

Citation(s):

Kearon C et al. for the Extended Low-Intensity Anticoagulation for Thrombo-Embolism Investigators. Comparison of low-intensity warfarin therapy with conventional-intensity warfarin therapy for long-term prevention of recurrent venous thromboembolism. N Engl J Med 2003 Aug 14; 349:631-9.

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• Medline abstract (Free)

Büller HR and Prins MH. Secondary prophylaxis with warfarin for venous thromboembolism. N Engl J Med 2003 Aug 14; 349:702-4.

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• Medline abstract (Free)