Standard
therapy for patients with
deep venous thrombosis and
pulmonary embolism typically includes anticoagulation for a 3-6 month period with full dose
warfarin. However, patients following this regimen experience high rates of recurrent
thrombosis, re-hospitalization and mortality in the years immediately following cessation of anticoagulation. This is true for patients at average risk of disease recurrence, and for patients at elevated risk due to the presence of inherited defects of anticoagulation such as
factor V Leiden mutation. Unfortunately, no clinical regimen currently available has proven to have sufficient benefit to support long-term prophylaxis. In particular, full dose
warfarin is associated with substantially increased risks of
hemorrhage when used on a long term basis. In contrast, while targeted low-dose
warfarin (INR 1.5-2.0) is safe for long-term
therapy, the efficacy of this approach in the prevention of recurrent venous thromboembolic disease has remained untested. The Prevention of Recurrent
Venous Thromboembolism (PREVENT) trial will evaluate the efficacy of prolonged treatment with low-dose
warfarin in the
secondary prevention of
venous thromboembolism (VTE). Patients with a history of documented idiopathic
venous thrombosis who have completed a standard course of anticoagulation
therapy will be enrolled in a randomized, double-blind, placebo-controlled trial comparing usual care plus targeted low-dose
warfarin to usual care plus placebo for a period of up to 4 years. Trial endpoints will include recurrent VTE, major
bleeding episodes and all-cause mortality in the total patient population and separately in those patients with
factor V Leiden. The potential clinical impact of the PREVENT trial is broad since a positive finding would strongly support chronic low-intensity anticoagulation among patients with
venous thrombosis who are at risk for recurrence following cessation of standard outpatient anticoagulation.