Initial Outpatient Treatment of Venous Thromboembolism with Fondaparinux (Arixtra®): The Matisse Trials.

Abstract

Background: The MATISSE trials showed that a single dose regimen of fondaparinux, a synthetic selective factor Xa inhibitor, was at least as effective and as safe as standard therapies in the treatment of venous thromboembolism (VTE). In these trials, outpatient treatment of fondaparinux was encouraged but left at the investigator's discretion. We analyzed the data in patients who received fondaparinux on an outpatient basis.Methods: Fondaparinux was administered at a once-daily subcutaneous dose of 7.5 mg (5.0 mg and 10.0 mg in patients <50 kg and >100 kg, respectively). In the MATISSE-DVT trial, fondaparinux was compared with twice-daily subcutaneous enoxaparin (1 mg/kg) in patients with deep-vein thrombosis (DVT). In the MATISSE-PE trial, it was compared with adjusted-dose intravenous unfractionated heparin (UFH) in patients with pulmonary embolism (PE). Outpatient treatment of DVT with enoxaparin was possible whereas outpatient treatment of PE with UFH was not feasible. All drugs were given for at least 5 days and until anticoagulation with oral anticoagulants was therapeutic. The primary efficacy and safety outcomes were recurrent VTE during 3 months' follow-up and major bleeding (MB) and death during the initial treatment period.Results: In MATISSE-DVT, 31.4% and 33.8% of the fondaparinux- and enoxaparin-treated patients, respectively, received therapy on an outpatient basis. In MATISSE-PE, 14.3% of the patients received fondaparinux on an outpatient basis, compared with none in the UFH group. In both MATISSE-DVT and -PE, efficacy and safety data from the patients who received fondaparinux on an outpatient basis were similar to those from the total population (Tables). The rates of recurrent VTE and MB in fondaparinux outpatients were similar to those in enoxaparin outpatients or UFH inpatients.Conclusion: Outpatient initial treatment of both DVT and PE with once-daily fondaparinux is feasible, effective and safe.MATISSE DVTEnoxaparinFondaparinuxAll patientsOutpatientsAll patientsOutpatientsn1107374 (33.8%)1098345 (31.4%)Age, yr (mean±SD)61±1760±1661±1758±17Male/female578/529201/173581/517197/148Hospital discharge, days (mean±SD)7.0±6.21.8±1.97.6±7.71.6±1.7≥2 VTE risk factors, n (%)283 (25.6)122 (32.6)293 (26.7)97 (28.1)VTE, n (%)45 (4.1)16 (4.3)43 (3.9)7 (2.0)MB*, n (%)13 (1.2)3 (0.8)12 (1.1)5 (1.5)*As treated patientsMATISSE-PEUFHFondaparinuxAll patientsOutpatientsn11101103158 (14.3%)Age, yr (mean±SD)62±1763±1657±16Male/female477/633501/60182/76Hospital discharge, days (mean±SD)10.2±6.89.7±7.74.4±2.2≥2 VTE risk factors, n (%)260 (23.4)241 (21.8)35 (22.2)VTE, n (%)56 (5.0)42 (3.8)5 (3.2)MB*, n (%)12 (1.1)14 (1.3)0 (0)*As treated patients