title: Factor Xa and thrombin as targets for new oral anticoagulants.
abstract: Although currently available anticoagulants are effective for the prevention and treatment of thromboembolic disorders, they have several drawbacks. Low molecular weight heparin and fondaparinux produce a predictable level of anticoagulation that obviates the need for coagulation monitoring, but they must be given parenterally, which renders them inconvenient for long-term use. Vitamin K antagonists, such as warfarin, are administered orally, but produce a variable anticoagulant response because genetic polymorphisms, dietary vitamin K intake and multiple drug-drug interactions affect their metabolism. Consequently, coagulation monitoring and frequent dose adjustments are needed to ensure that a therapeutic level of anticoagulation is achieved. This is burdensome for patients and physicians, and costly for the healthcare system. These limitations have prompted the development of new oral anticoagulants that target thrombin or factor Xa. The new agents produce such a predictable anticoagulant response that they can be given in fixed doses without monitoring. This paper focuses on the new oral anticoagulants in the most advanced stages of development.
authors.affiliation: Departments of Medicine and Biochemistry and Biomedical Sciences, McMaster University and Thrombosis and Atherosclerosis Research Institute, Hamilton, Ontario, Canada. weitzj@taari.ca
authors.forename: Jeffrey I
authors.initials: JI
authors.lastname: Weitz
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy; D000284:Administration, Oral; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D001281:Atrial Fibrillation / Q000150:complications / Q000188:drug therapy; D001562:Benzimidazoles / Q000008:administration & dosage; D002986:Clinical Trials as Topic; D000069604:Dabigatran; D055808:Drug Discovery; D065427:Factor Xa Inhibitors; D006801:Humans; D009025:Morpholines / Q000008:administration & dosage; D011720:Pyrazoles / Q000008:administration & dosage; D011725:Pyridines / Q000008:administration & dosage; D011728:Pyridones / Q000008:administration & dosage; D000069552:Rivaroxaban; D020521:Stroke / Q000517:prevention & control; D013844:Thiazoles / Q000008:administration & dosage; D013876:Thiophenes / Q000008:administration & dosage; D013917:Thrombin / Q000037:antagonists & inhibitors*; D054556:Venous Thromboembolism / Q000188:drug therapy / Q000517:prevention & control; D014812:Vitamin K / Q000037:antagonists & inhibitors
chemical_list: D000925:Anticoagulants; D001562:Benzimidazoles; D065427:Factor Xa Inhibitors; D009025:Morpholines; D011720:Pyrazoles; D011725:Pyridines; D011728:Pyridones; D013844:Thiazoles; D013876:Thiophenes; D014812:Vitamin K; C522181:apixaban; D000069552:Rivaroxaban; D013917:Thrombin; D000069604:Dabigatran; C552171:edoxaban