Lifetime Warfarin Prophylaxis Against Recurrent VTE
The trial of Kearon and the ELATE investigators(1) comparing
conventional warfarin with low-intensity warfarin for extended venous
thromboembolism (VTE) prophylaxis concluded that lifetime conventional
warfarin should become the standard of care for those with idiopathic VTE.
I disagree. The PREVENT trial(2) comparing low-intensity warfarin with
placebo was inadequate to prove that long-term low-intensity warfarin
should become the standard of care.(3) Therefore, to assess benefits
versus risks of lifetime adjusted dose warfarin as a new therapy, an
untreated control group must be included in the trial. In the recent
trial, 1% and 0% of patients had major and fatal bleeding each year,
respectively. However, two meta-analyses of prospective studies involving
conventional warfarin found the average yearly rates of bleeding to be
higher (major = 1.7%(4) and 3.0%(5), fatal = 0.8%(4) and 0.6%(5)).
Consequently, for each 100,000 VTE patients on extended warfarin
treatment, the meta-analyses bleeding rates translate to 1,700 – 3,000
major hemorrhages and 600 – 800 bleeding deaths per year. No trial of
extended warfarin for VTE has shown a significant reduction in fatal PE.
The risks of extended warfarin for VTE outweigh the benefits.
David K. Cundiff
1. Kearon C, Ginsberg JS, Kovacs MJ, et al. Comparison of Low-
Intensity Warfarin Therapy with Conventional-Intensity Warfarin Therapy
for Long-Term Prevention of Recurrent Venous Thromboembolism. The Extended
Low-Intensity Anticoagulation for Thrombo-Embolism Investigators. N Engl J
Med 2003; 349:631-639.
2. Ridker PM, Goldhaber SZ, Danielson E, et al. Long-Term, Low-
Intensity Warfarin Therapy for the Prevention of Recurrent Venous
Thromboembolism. N Engl J Med 2003; 348:1425-34.
3. Cundiff DK. Insufficient evidence supporting low-intensity warfarin for
venous thromboembolism (VTE) prophylaxis--Commentary. MedGenMed 2003;
4. Levine MN, Hirsh J, Landefeld S, Raskob G. Hemorrhagic
complications of anticoagulant treatment. Chest 1992; 102:352S-363S.
5. Landefeld CS, Beyth RJ. Anticoagulant-related bleeding: clinical
epidemiology, prediction, and prevention. American Journal of Medicine
I lost my license to practice medicine in the United States because I stopped warfarin treatment of an alcoholic with a DVT.
Competing interests: No competing interests