Direct thrombin inhibitor melagatran followed by oral ximelagatran in comparison with enoxaparin for prevention of venous thromboembolism after total hip or knee replacement The METHRO III study
Bengt I. Eriksson (1), Giancarlo Agnelli (2), Alexander T. Cohen (3), Ola E. Dahl (4), Patrick Mouret (5), Nadia Rosencher (6), Christina Eskilson (7), Ingela Nylander (7), Lars Frison (7), Mats Ögren (7), on behalf of the METHRO III Study Group* (* see
(1) Department of Orthopaedics, Sahlgrenska University Hospital/Östra, Göteborg, Sweden, (2) Division of Internal and Cardiovascular Medicine, University of Perugia, Perugia, Italy, (3) Department of Academic Surgery, Guy’s, King’s,Thomas’ School of Medi
Summary We evaluated whether a postoperative regimen with melagatranfollowed by oral ximelagatran, two new direct thrombininhibitors, was an optimal regimen for thromboprophylaxis inmajor orthopaedic surgery. In a double-blind study, 2788 patientsundergoing total hip or knee replacement were randomly assignedto receive for 8 to 11 days either 3 mg of subcutaneousmelagatran started 4-12 h postoperatively, followed by 24 mg oforal ximelagatran twice-daily or 40 mg of subcutaneous enoxaparinonce-daily, started 12 h preoperatively. Ximelagatran was to be initiated within the first two postoperative days. Theprimary efficacy endpoint was venous thromboembolism(deep-vein thrombosis detected by mandatory venography,pulmonary embolism or unexplained death). The main safetyendpoint was bleeding.Venous thromboembolism occurred in355/1146 (31.0%) and 306/1122 (27.3%) patients in the ximelagatranand enoxaparin group, respectively, a difference in riskof 3.7% in favour of enoxaparin (p = 0.053). Bleeding was comparablebetween the two groups.