Comparison of the Recanalization Rate and Incidence of Postthrombotic Syndrome in Patients With Lower-limb Deep Venous Thrombosis Treated With Rivaroxaban or Warfarin

This study was approved by the Research Ethics Committee of the Hospital do Servidor Público Estadual, São Paulo, Brazil, and was registered at clinicaltrials.gov under NCT 02704598. This prospective, randomized, consecutive, double-blind cohort study included patients treated for acute iliofemoral and/or femoropopliteal DVT of a lower limb at the Division of Vascular and Endovascular Surgery, Hospital do Servidor Público Estadual, São Paulo, Brazil, between march 2016 and July 2018. The patient data were collected during an appointment at the routine follow-up, and recorded with the proper protocols. The data obtained included the patient's general and demographic characteristics, and the information recorded during the outpatient follow-up visits. This research received no specific funding.

The noninclusion criteria were: pregnancy, age < 18 years or > 80 years, chronic renal failure, chronic hepatic chronic failure, inferior vena cava thrombosis, contraindication for any type of anticoagulation, previous DVT on the ipsilateral affected limb, or any type of active cancer, and patients who refused to participate in the study.

The exclusion criteria were: several hemorrhagic complications that required the discontinuation of anticoagulation, death after < 30 days, allergic reaction to any anticoagulant, a diagnosis of active cancer during follow-up, loss to follow-up, difficulty in achieving proper anticoagulation due to patient nonadherence to the treatment protocol, and incomplete data.

The diagnosis of DVT was made with clinical signs and symptoms, laboratory tests such as D-dimer, and routine DUS of the affected limb. The criteria used to confirm acute DVT with DUS were the absence or diminution of venous flow, incompressibility of the vessel, visible thrombus, enlarged vein diameter, immobility of the valves, and loss of respiratory phasicity.13 All the patients diagnosed with acute DVT were hospitalized and received initial anticoagulation with subcutaneous enoxaparin (1 mg/kg/dose) every 12 h (12/12 h) or intravenous unfractionated heparin (IUH) (loading dose 80 UI/kg, and 18 UI/kg/h) for at least 48-72 h. The infusion dose of IUH was adjusted to achieve the therapeutic activated partial thromboplastin time (APTT) established by the hospital laboratory within every 4-6 h period. After initial admission, the patients were randomized into two groups: group 1 patients received oral rivaroxaban, with a loading dose of 15 mg 12/12 h for 21 days after the initial dose, and 20 mg/day for 6 months; group 2 patients received oral warfarin, sufficient to maintain an INR of 2-3 for 6 months. The patients in group 2 were kept in hospital on subcutaneous enoxaparin or intravenous unfractionated heparin until their INR was 2-3. The patients were discharged after their INR achieved the therapeutic dose.

During the follow-up visits, all the patients were subjected to a DUS analysis by a physician blinded to the type of drug therapy, with defined protocols that assessed the compressibility of the external iliac vein, common femoral vein, superficial femoral vein, and popliteal vein. Flow recanalization was evaluated by confirming the total vein flow, the partial vein flow, or the absence of vein flow. All vessels evaluated were tested for the absence or presence of reflux and the grade of reflux.