New anticoagulants for venous thromboembolic disease.
OBJECTIVE
In this paper, recent advances in new anticoagulants with the potential to be used for prevention or treatment of venous thrombosis are reviewed.


RESULTS
Numerous novel anticoagulants targeting specific stages of the coagulant pathway are in various stages of development. Fondaparinux, an indirect activated factor VII inhibitor, has been shown to be effective for initial treatment and prevention of venous thromboembolism, but still requires parenteral administration. Ximelagatran, an oral direct thrombin inhibitor, has also been shown to effective for treatment and prevention of venous thrombosis. Both agents are associated with bleeding, however, and ximelagatran is associated with hepatic toxicity with long-term use. Direct activated factor X inhibitors, orally available forms of heparin, and other direct thrombin inhibitors remain in early stages of development. Further data on the clinical utility of these agents are likely to emerge in the next few years, and uptake of their use will be affected by the cost considerations.


CONCLUSIONS
Numerous alternative anticoagulants are in varying stages of development. Clinical data have yet to show that these agents have a clearly superior risk-benefit ratio compared with currently used antithrombotics. Many drugs remain in initial stages of development. The ideal anticoagulant agent is being sought but has yet to be discovered.
McRae
Simon J
SJ
Department of Medicine, McMaster University, Hamilton, Ontario, Canada. smcrae@mcmaster.ca
Ginsberg
Jeffrey S
JS
D000925:Anticoagulants / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001384:Azetidines / Q000494:pharmacology / Q000627:therapeutic use*; D001596:Benzylamines / Q000494:pharmacology / Q000627:therapeutic use*; D015942:Factor VIIa / Q000037:antagonists & inhibitors*; D000077425:Fondaparinux; D006493:Heparin / Q000009:adverse effects; D006801:Humans; D011134:Polysaccharides / Q000494:pharmacology / Q000627:therapeutic use*; D013917:Thrombin / Q000037:antagonists & inhibitors; D013921:Thrombocytopenia / Q000139:chemically induced / Q000188:drug therapy; D020246:Venous Thrombosis / Q000188:drug therapy* / Q000517:prevention & control
D000925:Anticoagulants; D001384:Azetidines; D001596:Benzylamines; D011134:Polysaccharides; C426686:ximelagatran; D006493:Heparin; D015942:Factor VIIa; D013917:Thrombin; D000077425:Fondaparinux