Clinical trials of new anticoagulants.
Shortcomings of the existing anticoagulants, vitamin K antagonists and heparins, have led to the development of newer anticoagulant therapies. In particular, Vitamin K antagonists' slow onset of action, numerous drug interactions, narrow therapeutic window and need for frequent monitoring make it the most obvious target for replacement. Targeting specific coagulation enzymes or steps in the coagulation pathway, new anticoagulants have been or are under evaluation in clinical trials for a number of clinical indications, namely the prevention and treatment of venous thromboembolism, the prevention of ischemic stroke in patients with atrial fibrillation, and in acute coronary syndromes. Following a brief review of pharmacological aspects, this article will summarize the results of Phase III clinical trials evaluating the novel anticoagulants fondaparinux, ximelagatran and idraparinux. At present, most attention is directed at developing an oral anticoagulant to replace vitamin K antagonists for prevention of systemic thromboembolism. A number of newer agents are in both early and advanced stages of investigation.
Anderson
J
J
Henderson Research Center and McMaster University, Hamilton, Ontario, Canada. jander@mcmaster.ca
O'Donnell
M
M
D000925:Anticoagulants / Q000494:pharmacology / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000150:complications; D001384:Azetidines / Q000494:pharmacology / Q000627:therapeutic use*; D001596:Benzylamines / Q000494:pharmacology / Q000627:therapeutic use*; D017326:Clinical Trials, Phase III as Topic; D000077425:Fondaparinux; D006801:Humans; D009844:Oligosaccharides / Q000494:pharmacology / Q000627:therapeutic use*; D011134:Polysaccharides / Q000494:pharmacology / Q000627:therapeutic use*; D013923:Thromboembolism / Q000188:drug therapy / Q000517:prevention & control; D013927:Thrombosis / Q000209:etiology / Q000517:prevention & control; D020246:Venous Thrombosis / Q000188:drug therapy / Q000517:prevention & control
D000925:Anticoagulants; D001384:Azetidines; D001596:Benzylamines; D009844:Oligosaccharides; D011134:Polysaccharides; C426686:ximelagatran; C479958:idraparinux; D000077425:Fondaparinux