New anticoagulants for treatment of venous thromboembolism.
Anticoagulant therapy is the cornerstone of treatment of venous thromboembolism (VTE). Such treatment is divided into 2 stages: Rapid initial anticoagulation is given to minimize the risk of thrombus extension and fatal pulmonary embolism, whereas extended anticoagulation is aimed at preventing recurrent VTE, thereby reducing the risk of postphlebitic syndrome. With currently available drugs, immediate anticoagulation can only be achieved with parenteral agents, such as heparin, low-molecular-weight heparin, or fondaparinux. Extended treatment usually involves the administration of vitamin K antagonists, such as warfarin. Emerging anticoagulants have the potential to streamline VTE treatment. These agents include idraparinux, a long-acting synthetic pentasaccharide that is given subcutaneously on a once-weekly basis, and new oral anticoagulants that target thrombin or factor Xa. This article (1) reviews the pharmacology of these agents, (2) outlines their potential strengths and weaknesses, (3) describes the results of clinical trials with these new drugs, and (4) identifies the evolving role of new anticoagulants in the management of VTE.
Gross
Peter L
PL
Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
Weitz
Jeffrey I
JI
D000284:Administration, Oral; D000925:Anticoagulants / Q000494:pharmacology / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000627:therapeutic use; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D000069604:Dabigatran; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D020714:Maximum Tolerated Dose; D009025:Morpholines / Q000627:therapeutic use; D009844:Oligosaccharides / Q000627:therapeutic use; D011186:Postphlebitic Syndrome / Q000517:prevention & control*; D011379:Prognosis; D011720:Pyrazoles / Q000627:therapeutic use; D011725:Pyridines / Q000627:therapeutic use; D011728:Pyridones / Q000627:therapeutic use; D000069552:Rivaroxaban; D016019:Survival Analysis; D013876:Thiophenes / Q000627:therapeutic use; D016896:Treatment Outcome; D054556:Venous Thromboembolism / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality*
D000925:Anticoagulants; D001562:Benzimidazoles; D009025:Morpholines; D009844:Oligosaccharides; D011720:Pyrazoles; D011725:Pyridines; D011728:Pyridones; D013876:Thiophenes; C522181:apixaban; C479958:idraparinux; D000069552:Rivaroxaban; D000069604:Dabigatran