Venous thromboembolism is a common and serious disease. The term venous thromboembolism encompasses two different manifestations of the same disease process. Deep vein thrombosis (DVT) occurs when a blood clot develops in the deep veins of the body, usually in the legs, greatly reducing or blocking blood flow. Pulmonary embolism (PE) occurs when this clot breaks loose, travels through the bloodstream, and partially or completely blocks an artery in the lungs. Current estimates state that approximately half a million Americans experience either DVT or PE every year.

For many, the primary risk factors for DVT/PE are long periods of inactivity, which decrease blood circulation. For example, people who are bedridden for long periods of time after surgery, have suffered a serious injury, or have a chronic illness, or travelers on long trips (Economy Class Syndrome) are among those at greatest risk of DVT/PE. However, some patients are predisposed to venous thromboembolism due to their heredity or an acquired chronic disease (such as certain cancers), placing them at increased risk of DVT/PE, particularly if they experience one of the risk factors listed above.

Traditionally, patients who experienced DVT/PE were treated with high doses of warfarin (an anti-clotting agent) for up to a year as a means of preventing a recurrence. However, warfarin’s anti-clotting effects also left these patients at risk of severe hemorrhage. The Prevention of Recurrent Venous Thromboembolism (PREVENT) trial was initiated to explore long-term, low-dose warfarin as a safe and effective therapy for reducing the risk of recurrent DVT/PE. The results of the study, which will be published in the April 10, 2003 issue of the New England Journal of Medicine were released early because the findings have immediate implications for patients. The study concluded that low-dose warfarin is a highly effective way of preventing recurrent DVT/PE with low risks of complications.

About the Study

The study enrolled 502 patients at 52 clinical sites throughout the U.S., Canada, and Switzerland. The patients were followed for an average of two years. All participants in the study were at least 30 years old, had a history of DVT/PE within the past two years, and had been treated with full-dose warfarin (Coumadin) continuously for at least 3 months. Full-dose warfarin was defined in the study as a sufficient dose to achieve 2.0 to 3.0 international normalized ratios (INRs), which is a standard measure of anti-clotting effect. This required daily doses ranging between 2 milligrams (mg) and 10 mg.

The patients in the study were randomly assigned to receive treatment with either low-dose warfarin or placebo. Low-dose warfarin was defined in the study as a sufficient does to achieve an INR of 1.5 to 2.0.

The Findings

Of the 255 patients who received low-dose warfarin, only 14 experienced a recurrent episode of DVT/PE, compared with 37 of the 253 patients in the placebo group. This translated into a 64% reduction in the risk of DVT/PE for patients receiving low-dose warfarin treatment. These results were consistent for all ages and genders. Two patients in the placebo group and five in the warfarin group experienced bleeding events (hemorrhage). Among the five in the warfarin group, only one of the patients experiencing hemorrhage required hospitalization and transfusion.

This study resulted in such a high degree of benefit to the patients that the National Heart, Lung, and Blood Institute (NHLBI) stopped the study early because the safety board reviewing the results felt that it would be unethical to continue giving placebos to patients in the control groups.

How Does This Affect You?

Until now, there has been no proven long-term therapy available to patients at risk for recurrent DVT/PE. In the past, these patients were treated with high doses of warfarin for 3 to 6 months, after which treatment was stopped to avoid the risk of hemorrhage. Unfortunately, this left these patients at risk for recurrent DVT/PE.

This study found that after the initial three-month treatment with high-dose warfarin, lowering the warfarin dose and maintaining the treatment regimen could prevent recurrent episodes of DVT/PE. This regimen provides continued protection from DVT/PE, without increasing the risk for hemorrhage.

The PREVENT researchers strongly recommend this new treatment regimen be adopted immediately as a new standard of care for the management of venous thromboembolism after stopping full-dose warfarin therapy.