THE DURATION OF ORAL ANTICOAGULANT-THERAPY AFTER A 2ND EPISODE OF VENOUS THROMBOEMBOLISM

Background A consensus has not been reached about the optimal duration of oral anticoagulant therapy after a second episode of venous thromb oembolism. Methods In a multicenter trial, we compared six months of o ral anticoagulant therapy with anticoagulant therapy continued indefin itely in patients who had had a second episode of venous thromboemboli sm. Of 227 patients enrolled, 111 were randomly assigned to six months of anticoagulation and 116 were assigned to receive anticoagulant the rapy indefinitely; for both groups, the target international normalize d ratio was 2.0 to 2.85. The initial episodes of deep-vein thrombosis (n = 193) and pulmonary embolism (n = 34), as well as recurrent episod es, were all objectively confirmed. Results After four years of follow -up, there were 26 recurrences of venous thromboembolism that fulfille d the diagnostic criteria, 23 in the group assigned to six months of t herapy (20.7 percent) and 3 in the group assigned to continuing therap y (2.6 percent). The relative risk of recurrence in the group assigned to six months of therapy, as compared with the group assigned to ther apy of indefinite duration, was 8.0 (95 percent confidence interval, 2 .5 to 25.9). There were 13 major hemorrhages, 3 in the six-month group (2.7 percent) and 10 in the indefinite-treatment group (8.6 percent). The relative risk of major hemorrhage in the six-month group, as comp ared with the indefinite-treatment group, was 0.3 (95 percent confiden ce interval, 0.1 to 1.1). There was no difference in mortality between the two groups. Conclusions Prophylactic oral anticoagulation that wa s continued for an indefinite period after a second episode of venous thromboembolism was associated with a much lower rate of recurrence du ring four years of follow-up than treatment for six months. However, t here was a trend toward a higher risk of major hemorrhage when anticoa gulation was continued indefinitely. (C) 1997, Massachusetts Medical S ociety.