Extended Oral Anticoagulant Therapy after a First Episode of Pulmonary Embolism

Background: The optimal duration of oral anticoagulant treatment after a first episode of pulmonary embolism remains uncertain. Objective: To evaluate the long-term clinical benefit of extending a 3-month course of oral anticoagulant therapy to 6 months (pulmonary embolism associated with temporary risk factors) or to 1 year (idiopathic pulmonary embolism) in patients with a first episode of pulmonary embolism. Design: Multicenter randomized study with independent, blinded assessment of the outcome events. Setting: 19 Italian hospitals. Patients: 326 patients who had had 3 months of oral anticoagulant therapy without experiencing recurrence or bleeding. Measurements: The primary study outcome was recurrence of symptomatic, objectively confirmed venous thromboembolism. Results: Among 165 patients assigned to extended anticoagulant therapy, 15 patients (9.1%) had a recurrence of venous thromboembolism (3.1% per patient-year; average follow-up, 34.9 months), as compared with 18 of 161 patients (11.2%) assigned to discontinue treatment (4.1% per patient-year; average follow-up, 32.7 months); the rate ratio was 0.81 (95% CI, 0.42 to 1.56). All but one of the recurrences occurred after anticoagulant treatment was discontinued. Nineteen recurrences (57.6%) were episodes of pulmonary embolism, two of which were fatal. Three major bleeding episodes were observed during extended anticoagulation (1.8%). Among patients with idiopathic venous thromboembolism, 11 of 90 patients assigned to extended anticoagulation and 11 of 91 patients assigned to discontinue treatment experienced a recurrence (relative risk, 0.99 [CI, 0.45 to 2.16]). Conclusion: Patients with pulmonary embolism have a substantial risk for recurrence after discontinuation of oral anticoagulation, regardless of treatment duration. Physicians should try to identify patients who are at high risk for recurrent venous thromboembolism and are therefore potential candidates for indefinite oral anticoagulant therapy. *For a list of the Warfarin Optimal Duration Italian Trial Investigators, see Appendix.