FIXED DOSE ORAL XIMELAGATRAN IS EFFICACIOUS AND WELL TOLERATED AS THROMBOPROPHYLAXIS AFTER TOTAL HIP REPLACEMENT OR TOTAL KNEE REPLACEMENT

Abstract

Ximelagatran is an oral direct thrombin inhibitor intended for the prophylaxis and treatment of thrombo-embolic complications. Purpose: The efficacy and safety of ximelagatran, and its subcutaneous (sc) form melagatran, were evaluated in patients undergoing total hip or knee replacement (THR, TKR). Study 1 was a randomised, double-blind, controlled, dose–response study in which patients received 2-6 doses of sc melagatran (1, 1.5, 2.25, or 3 mg bid) followed by oral ximelagatran (8, 12, 18, or 24 mg bid), or sc dalteparin (5000 IU od). Melagatran treatment was initiated immediately before surgery. Study 2 was a randomized, double-blind, controlled study in which patients received 1–5 doses of sc melagatran (3 mg bid) initiated 4–12 h after surgery followed by oral ximelagatran (24 mg bid), or sc enoxaparin (40 mg od). In both studies, low-molecular-weight heparin (LMWH) was started the evening before surgery, and all treatment regimens were continued for 8–11 days. Bilateral venography was performed on the final day of treatment.

Results: In Study 1, 1876 patients underwent THR (n=1270) or TKR (n=606). A significant dose-dependent reduction in venous thromboembolism (VTE) was seen with melagatran + ximelagatran for both THR (P< 0.0001) and TKR (P=0.0014). The rate of VTE was significantly lower with the highest dose of melagatran + ximelagatran (15.1%) when compared with dalteparin (28.2%) (P< 0.0001). In Study 2, 2788 patients underwent THR (n=1923) or TKR (n=865). The VTE rate was 31% in the melagatran + ximelagatran group and 27% in the enoxaparin group (P=0.053). Total bleeding volume was not significantly different between treatment groups. Conclusion: Fixed-dose sc melagatran followed by oral ximelagatran are efficacious and well tolerated for the prophylaxis of VTE following THR or TKR.