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Ximelagatran vs. Enoxaparin/Warfarin for VTE
Ximelagatran continues to show promise for secondary prevention of venous thromboembolism, but concerns about liver-enzyme elevations persist.
Ximelagatran, an oral direct thrombin inhibitor that does not require coagulation monitoring, has been shown to be effective for long-term secondary prevention of venous thromboembolism (VTE; Journal Watch Cardiology Feb 13 2004). Now, researchers have conducted a multinational, manufacturer-funded, randomized trial of ximelagatran (36 mg twice daily) versus standard therapy with enoxaparin (1 mg/kg for 5-20 days) followed by warfarin (target INR, 2.0-3.0) in 2489 patients with acute deep-vein thrombosis (DVT). About one third of subjects also had pulmonary embolism. Treatment lasted 6 months.
The incidence of recurrent VTE at 6 months was similar with ximelagatran (2.2%) and enoxaparin/warfarin (2.0%), demonstrating the noninferiority of ximelagatran. The ximelagatran group also showed nonsignificant trends toward less major bleeding (1.3% vs. 2.2% with enoxaparin/warfarin) and lower mortality (2.3% vs. 3.4%).
Increases in serum alanine aminotransferase to >3 times the upper limit of normal occurred in 9.6% of the ximelagatran group and 2.0% of the enoxaparin/warfarin group. Post hoc analyses documented 10 adverse coronary events with ximelagatran and 1 with enoxaparin/warfarin.
Comment: In patients with DVT (with or without pulmonary embolism), a fixed dose of oral ximelagatran was as effective as enoxaparin/warfarin for preventing recurrence, without excess risk for major bleeding. However, the higher rates of liver-enzyme elevations and coronary events with ximelagatran are troubling, although the latter was uncovered only retrospectively. Still, both findings require further study before this therapy can be adopted broadly for VTE. The FDA has not approved ximelagatran for long-term secondary prevention after standard treatment for acute VTE.
— JoAnne M. Foody, MD
Published in Journal Watch Cardiology March 25, 2005
Citation(s):
Fiessinger JN et al. for the THRIVE Treatment Study Investigators. Ximelagatran vs low-molecular-weight heparin and warfarin for the treatment of deep vein thrombosis: A randomized trial. JAMA 2005 Feb 9; 293:681-9.
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