title: New anticoagulants.
abstract: OBJECTIVE
  Although current anticoagulants such as unfractionated and low-molecular-weight heparins and the vitamin K antagonists are effective for the prevention and treatment of thrombosis, they have several limitations. The vitamin K antagonists, the only approved oral anticoagulants, have a narrow therapeutic window, thereby requiring regular laboratory monitoring of the international normalized ratio and intermittent adjustments in dose. New anticoagulants have been developed that selectively inhibit thrombin or factor Xa, and have predictable dose-response relationships.
  
  
  RESULTS
  Fondaparinux is a synthetic pentasaccharide, which binds to antithrombin, thereby indirectly inhibiting factor Xa. Fondaparinux demonstrated efficacy compared with low-molecular-weight heparin in randomized clinical trials and is approved for the prevention and treatment of venous thromboembolism. A number of oral direct factor Xa inhibitors and oral direct thrombin inhibitors are in advanced phases of clinical development for the prevention and treatment of thrombosis. The current status of these anticoagulants will be reviewed along with the challenges faced in designing pivotal clinical trials of these agents in comparison to existing anticoagulants.
  
  
  CONCLUSIONS
  Selective inhibitors of specific coagulation factors have the potential to be more effective, safer, and easier to use than existing anticoagulants. Approval of one or more of these agents will lead to an improved drug armamentarium for the prevention and treatment of thrombosis.
authors.affiliation: VA Boston Healthcare System and Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA. kbauer@bidmc.harvard.edu
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Bauer
mesh_terms: D000925:Anticoagulants / Q000627:therapeutic use*; D000990:Antithrombin III / Q000627:therapeutic use; D001779:Blood Coagulation Factors / Q000037:antagonists & inhibitors; D000077425:Fondaparinux; D006801:Humans; D011134:Polysaccharides; D016896:Treatment Outcome
chemical_list: D000925:Anticoagulants; D001779:Blood Coagulation Factors; D011134:Polysaccharides; D000990:Antithrombin III; D000077425:Fondaparinux