Three months versus one year of oral anticoagulant therapy for idiopathic deep venous thrombosis. Warfarin Optimal Duration Italian Trial Investigators.

Background: In patients with idiopathic deep venous thrombosis, continuing anticoagulant therapy beyond three months is associated with a reduced incidence of recurrent thrombosis during the period of therapy. Whether this benefit persists after anticoagulant therapy is discontinued is controversial.

Methods: Patients with a first episode of idiopathic proximal deep venous thrombosis who had completed three months of oral anticoagulant therapy (with warfarin, in 97 percent of the cases and acenocoumarol in 3 percent) were randomly assigned to the discontinuation of oral anticoagulants or to their continuation for nine additional months. The primary study outcome was recurrence of symptomatic, objectively confirmed venous thromboembolism during at least two years of follow-up.

Results: The primary intention-to-treat analysis showed that of 134 patients assigned to continued oral anticoagulant therapy, 21 had a recurrence of venous thromboembolism (15.7 percent; average follow-up, 37.8 months), as compared with 21 of 133 patients assigned to the discontinuation of oral anticoagulant therapy (15.8 percent; average follow-up, 37.2 months), resulting in a relative risk of 0.99 (95 percent confidence interval, 0.57 to 1.73). During the initial nine months after randomization (after all patients received three months of therapy), 1 patient had a recurrence while receiving oral anticoagulant therapy (0.7 percent), as compared with 11 of the patients assigned to the discontinuation of oral anticoagulant therapy (8.3 percent; P=0.003). The incidence of recurrence after the discontinuation of treatment was 5.1 percent per patient-year in patients in whom oral anticoagulant therapy was discontinued after 3 months (95 percent confidence interval, 3.2 to 7.5 percent; average interval since discontinuation, 37.2 months) and 5.0 percent per patient-year in patients who received an additional 9 months of oral anticoagulant therapy (95 percent confidence interval, 3.1 to 7.8 percent; average interval since discontinuation, 29.4 months). None of the recurrences were fatal. Four patients had non-fatal major bleeding during the extended period of anticoagulant therapy (3.0 percent).

Conclusions: In patients with idiopathic deep venous thrombosis, the clinical benefit associated with extending the duration of anticoagulant therapy to one year is not maintained after the therapy is discontinued.