Ximelagatran, the new oral anticoagulant: would warfarin survive the challenge?
The last decade witnessed major advances in the prevention and treatment of venous as well as of arterial thrombosis. Limitations of existing anticoagulants led to the development of novel therapeutic approaches. Ximelagatran is a new direct thrombin inhibitor (DTI) that is given orally, without the need for close monitoring. This compound was tried in the treatment of active venous thromboembolism, and the results were encouraging. Randomized trials suggest that ximelagatran is not inferior to warfarin in the prevention of stroke in patients with nonvalvular atrial fibrillation. Multiple controlled, prospective trials compared ximelagatran with low molecular weight heparin or warfarin in prevention of venous thromboembolism in patients undergoing major orthopedic procedures. The results of these clinical trials are reviewed in this article. Because of certain safety concerns (increased liver enzymes, potential hepatonecrosis, and increased coronary events) ximelagatran has not yet been approved by the FDA. Additional studies may be required to address these concerns. Ximelagatran has been approved, however, by the European regulatory authorities for short-term thromboprophylaxis. The success of ximelagatran or other oral antithrombin agents would provide significant proof of the concept for the long-term use of oral antithrombins in the prevention and treatment of both arterial and venous thrombosis.
Mousa
Shaker A
SA
Albany College of Pharmacy, The Pharmaceutical Research Institute, Albany, NY 12208, USA. mousas@acp.edu
Abdel-Razeq
Hikmat N
HN
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology* / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000188:drug therapy / Q000517:prevention & control; D001384:Azetidines / Q000494:pharmacology* / Q000627:therapeutic use; D001596:Benzylamines / Q000494:pharmacology* / Q000627:therapeutic use; D006493:Heparin / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D013927:Thrombosis / Q000188:drug therapy / Q000517:prevention & control
D000925:Anticoagulants; D001384:Azetidines; D001596:Benzylamines; C426686:ximelagatran; D006493:Heparin