A Comparison of Three Months of Anticoagulation with Extended Anticoagulation for a First Episode of Idiopathic Venous Thromboembolism

作者：Clive Kearon, Michael Gent, Jack Hirsh, Jeffrey Ian Weitz, Michael J. Kovacs, David R. Anderson, Alexander G.G. Turpie, David Green, Jeffrey S. Ginsberg, Philip S. Wells, Betsy MacKinnon, Marilyn Johnston, James D. Douketis, Robin E. Roberts, Paul Nguyen, Jeannine Kassis, Sean Dolan, Christine Demers, Louis Desjardins, Susan Solymoss, Arthur A. Trowbridge, Jim A. Julian · 发表于：New England Journal of Medicine · 年份：1999 · DOI：10.1056/nejm199903253401201 · 被引用次数：1077 · 研究领域：Venous Thromboembolism Diagnosis and Management、Blood Coagulation and Thrombosis Mechanisms、Atrial Fibrillation Management and Outcomes

BACKGROUND: Patients who have a first episode of venous thromboembolism in the absence of known risk factors for thrombosis (idiopathic thrombosis) are often treated with anticoagulant therapy for three months. Such patients may benefit from longer treatment, however, because they appear to have an increased risk of recurrence after anticoagulant therapy is stopped. METHODS: In this double-blind study, we randomly assigned patients who had completed 3 months of anticoagulant therapy for a first episode of idiopathic venous thromboembolism to continue receiving warfarin, with the dose adjusted to achieve an international normalized ratio of 2.0 to 3.0, or to receive 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 termination 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 placebo, 17 had a recurrent episode of venous thromboembolism (27.4 percent per patient-year), as compared with 1 of 79 patients assigned to receive warfarin (1.3 percent per patient-year, P<0.001). Warfarin resulted in a 95 percent reduction in the risk of recurrent venous thromboembolism (95 percent confidence interval, 63 to 99 percent). Three patients assigned to the warfarin group had nonfatal major bleeding (two had gas...