Overview of Direct Thrombin Inhibitors in Clinical Practice

Novel anticoagulants have been developed that specifically target activated coagulation factor X or thrombin. This article reviews the present state of direct thrombin inhibitors, including compounds that are administered parenterally (lepirudin, bivalirudin, argatroban, napsagatran, and Melagatran [AstraZeneca, Mölndal, Sweden]) and those that can be given orally (ximelagatran and dabigatran etexilate). Lepirudin and argatroban (in the United States but not in all European countries) are licensed for treatment of heparin-induced thrombocytopenia (HIT) (argatroban also for prophylaxis), whereas bivalirudin is approved as an alternative to heparin in patients undergoing percutaneous coronary interventions (PCI) and argatroban for PCI in patients with HIT. Napsagatran development has ceased, and ximelagatran has not been granted approval by the U.S. Food and Drug Administration and was withdrawn from European market a few months after its initial registration due to liver toxicity. The compound with the most advanced development among the oral direct thrombin inhibitors at the present time is dabigatran etexilate, for which promising phase III data already exist for the indication of thromboprophylaxis following major orthopedic surgery. KEYWORDS Oral anticoagulants - direct thrombin inhibitors - lepirudin - argatroban - dabigatran