Medical indications and considerations for future clinical decision making.

摘要

There are many well-known drawbacks associated with the currently used antithrombotic agents, warfarin, heparin, and low-molecular-weight heparins (LMWHs). Because heparins can be administered only parenterally, their application is limited. Though warfarin can be administered orally, its unpredictable anticoagulant effect means that it must be regularly monitored. Ximelagatran (Exanta, AstraZeneca) is a novel, oral direct thrombin inhibitor (oral DTI) that is rapidly converted to its active form, melagatran, upon administration. The antithrombotic effects of melagatran have been demonstrated. Following the oral administration of ximelagatran, melagatran has stable and reproducible pharmacokinetic and pharmacodynamic properties that enable ximelagatran to be administered orally, twice daily, according to a fixed-dose regimen, with no need for routine coagulation monitoring. In view of its favourable profile, a clinical trial programme has been designed to evaluate the efficacy and tolerability of ximelagatran compared with standard therapies, for the prophylaxis and treatment of venous thromboembolism (VTE), the prevention of stroke in patients with atrial fibrillation (AF), and the prevention of cardiovascular events in patients with previous acute coronary syndromes. These studies show that oral ximelagatran is well tolerated at doses of up to 60 mg, twice daily (bid), and that it is as effective as standard therapy for the prevention of thromboembolic events in patients undergoing hip or knee replacement surgery, for the treatment of clinically verified acute deep vein thrombosis (DVT), and in patients with nonvalvular AF who have a moderate to high risk of stroke. The protocols and results of some of these studies-and a study that investigates the use of ximelagatran in combination with aspirin for the management of acute coronary artery disease-are described in this paper.