Residual thrombosis on ultrasonography to guide the duration of anticoagulation in patients with deep venous thrombosis: a randomized trial.

Background: The optimal duration of oral anticoagulant therapy in patients with deep venous thrombosis (DVT) of the lower extremities remains uncertain. Objective: To assess whether tailoring the duration of anticoagulation based on the ultrasound persistence of residual thrombi reduces the rate of recurrent venous thromboembolism (VTE) in comparison to the administration of conventional fixed duration in adults with proximal DVT. Design: Parallel randomized trial carried out between 1999 and 2006. Trained physicians who assessed outcomes, but neither patients nor their providers were blinded to patient assignment status. Setting: Nine university or hospital centers in Italy. Patients: 538 consecutive outpatients with the first episode of acute proximal DVT who had completed an uneventful 3-month period of anticoagulation. Intervention: Patients were randomized (stratified by center and secondary versus unprovoked DVT, computer generated centrally, accessible only to a trial nurse) to a fixed duration of anticoagulation (i.e., no further anticoagulation for secondary thrombosis, an extra 3-month for unprovoked thrombosis) or to a flexible duration of ultrasound-guided anticoagulation (i.e., no further anticoagulation in patients with recanalized veins, continuation of anticoagulation in all other patients up to a maximum of 9 months for secondary and 21 months for unprovoked thrombosis). 530 patients completed the trial for the primary outcome assessment. Measurements: The primary study outcome was to assess the rate of confirmed recurrent VTE during 33 months of follow-up. Results: Recurrent VTE developed in 46 (17.2%) of the 268 patients allocated to the fixed anticoagulant duration and in 32 (11.9%) of the 270 randomized to the flexible duration, for an adjusted hazard ratio (HR) of 0.64 (95% CI, 0.39 to 0.99). In unprovoked DVT the adjusted HR was 0.61 (95% CI, 0.36 to 1.02), while it was 0.81 (95% CI, 0.32 to 2.06) in secondary DVT. Major bleeding occurred in 2 (0.7%) patients in the fixed duration group and 4 (1.5%) in the flexible duration group (p=0.67). Study limitations: Lack of a double-blind design; sample size not powered enough to detect differences in bleeding between groups and to detect effectiveness of the intervention in the subgroups of patients with unprovoked and secondary DVT; exclusion from the study of patients with previous thromboembolism, permanent risk factors for thrombosis, and thrombophilic abnormalities other than factor V Leiden and prothrombin mutation. Conclusions: Tailoring the duration of anticoagulation based on ultrasound findings reduces the rate of recurrent VTE in adults with proximal DVT.