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.