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 on the basis of the persistence of residual thrombi on ultrasonography reduces the rate of recurrent venous thromboembolism (VTE) compared with the administration of conventional fixed-duration treatment in adults with proximal DVT.
Design: Parallel, randomized trial from 1999 to 2006. Trained physicians who assessed outcomes were blinded to patient assignment status, but patients and providers were not.
Setting: 9 university or hospital centers in Italy.
Patients: 538 consecutive outpatients with a first episode of acute proximal DVT at completion of an uneventful 3-month period of anticoagulation.
Intervention: Patients were randomly assigned (stratified by center and secondary vs. unprovoked DVT by using a computer-generated list that was accessible only to a trial nurse) to fixed-duration anticoagulation (no further anticoagulation for secondary thrombosis and an extra 3 months for unprovoked thrombosis) or flexible-duration, ultrasonography-guided anticoagulation (no further anticoagulation in patients with recanalized veins and continued anticoagulation in all other patients for up to 9 months for secondary DVT and up to 21 months for unprovoked thrombosis). For the primary outcome assessment, 530 patients completed the trial.
Measurements: The rate of confirmed recurrent VTE during 33 months of follow-up.
Results: Overall, 46 (17.2%) of 268 patients allocated to fixed-duration anticoagulation and 32 (11.9%) of 270 patients allocated to flexible-duration anticoagulation developed recurrent VTE (adjusted hazard ratio [HR], 0.64 [95% CI, 0.39 to 0.99]). For patients with unprovoked DVT, the adjusted HR was 0.61 (CI, 0.36 to 1.02) and 0.81 (CI, 0.32 to 2.06) for those with secondary DVT. Major bleeding occurred in 2 (0.7%) patients in the fixed-duration group and 4 (1.5%) patients in the flexible-duration group (P = 0.67).
Limitations: The trial lacked a double-blind design. The sample size was not powered to detect differences in bleeding between groups and to detect effectiveness of the intervention in the subgroups of patients with unprovoked and secondary DVT. Patients with previous thromboembolism, permanent risk factors for thrombosis, and thrombophilic abnormalities other than factor V Leiden and prothrombin mutation were excluded.
Conclusion: Tailoring the duration of anticoagulation on the basis of ultrasonography findings reduces the rate of recurrent VTE in adults with proximal DVT.
Primary funding source: None.
Trial registration: ClinicalTrials.gov NCT00380120.