Warfarin prevents recurrence of blood clots
Study shows no evidence of significant risks
A study of long-term, low-dose warfarin (Coumadin) in the prevention of blood-clotting disorders showed such promise that the National Institutes of Health, the trial’s sponsor, stopped the study early.
The multi-center Prevention of Recurrent Venous Thromboembolism (PREVENT) trial found a 64% reduction in episodes of deep vein thrombosis (DVT) and pulmonary embolism in study participants taking low-dose warfarin compared to those taking a placebo. In addition, there was no evidence of significant risks such as major hemorrhage or other potential side effects of warfarin.
Until now, the current standard treatment for DVT and pulmonary embolism not associated with surgery or another specific cause is five to 10 days of intravenous or subcutaneous heparin followed by three to six months of full-dose warfarin, with a target international normalized ratio (INR) between 2.0 and 3.0. Therapy typically stops after the initial treatment period because long-term use of full-dose warfarin is associated with a substantial risk of major bleeding.
In the PREVENT trial, 508 patients with idiopathic venous thromboembolism who had received full-dose anticoagulation therapy for a median of 6.5 months were randomly assigned to placebo or low-intensity warfarin (target INR, 1.5-2.0). Participants were followed for an average of about two years for recurrent venous thromboembolism, major hemorrhage, and death.
Of 253 patients assigned to placebo, 37 had recurrent venous thromboembolism, as compared with 14 of 255 patients assigned to low-intensity warfarin, a risk reduction of 64%. Major hemorrhage occurred in two patients assigned to placebo and five assigned to low-intensity warfarin. Eight patients in the placebo group and four in the group assigned to low-intensity warfarin died. An analysis that combined the numbers of recurrent blood clots/cases of pulmonary embolism with the number of hemorrhages and deaths found a 48% reduction in risk for patients assigned to warfarin.
"The PREVENT results strongly suggest that long-term use of low-intensity warfarin should be considered a new standard of care for the management of venous thrombosis after stopping full-dose warfarin therapy," says Paul Ridker, MD, the principal investigator of PREVENT, professor of medicine at Harvard University in Cambridge, MA, and director of the Center for Cardiovascular Disease Prevention at Brigham and Women’s Hospital in Boston.
The study gives a new use for a 50-year-old drug, Ridker says. In addition, warfarin is inexpensive and is available in generic form.
The study will appear in the April 10, 2003, issue of The New England Journal of Medicine (NEJM). NEJM, however, posted the results on its web site on Feb. 24 because of their importance.
In an accompanying editorial in NEJM, Andrew I. Schafer, MD, professor and chairman of the Department of Medicine of the University of Pennsylvania School of Medicine in Philadelphia, agrees that based on these data, it is reasonable for clinicians, "at least for now," to adopt this regimen. He notes that the recommendations may change with new research or as new drugs become available.
A study of long-term, low-dose warfarin (Coumadin) in the prevention of blood-clotting disorders showed such promise that the National Institutes of Health, the trials sponsor, stopped the study early.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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