A comparison of three months of anticoagulation with extended anticoagulation for a first episode of idiopathic venous thromboembolism

Background Patients who have a first episode of venous thromboembolism in t he absence of known risk factors for thrombosis (idiopathic thrombosis) are often treated with anticoagulant therapy for three months. Such patients m ay benefit from longer treatment, however, because they appear to have an i ncreased risk of recurrence after anticoagulant therapy is stopped. Methods In this double-blind study, we randomly assigned patients who had c ompleted 3 months of anticoagulant therapy for a first episode of idiopathi c venous thromboembolism to continue receiving warfarin, with the dose adju sted to achieve an international normalized ratio of 2.0 to 3.0, or to rece ive placebo for a further 24 months. Our goal was to determine the effects of extended anticoagulant therapy on rates of recurrent symptomatic venous thromboembolism and bleeding. Results A prespecified interim analysis of efficacy led to the early termin ation of the trial after 162 patients had been enrolled and followed for an average of 10 months. Of 83 patients assigned to continue to receive place bo, 17 had a recurrent episode of venous thromboembolism (27.4 percent per patient-year), as compared with 1 of 79 patients assigned to receive warfar in (1.3 percent per patient-year, P<0.001). Warfarin resulted in a 95 perce nt reduction in the risk of recurrent venous thromboembolism (95 percent co nfidence interval, 63 to 99 percent). Three patients assigned to the warfar in group had nonfatal major bleeding (two had gastrointestinal bleeding and one genitourinary bleeding), as compared with none of those assigned to th e placebo group (3.8 percent vs. 0 percent per patient-year, P=0.09). Conclusions Patients with a first episode of idiopathic venous thromboembol ism should be treated with anticoagulant agents for longer than three month s. (N Engl J Med 1999;340:901-7.) (C) 1999, Massachusetts Medical Society.