New anticoagulants.
BACKGROUND
Heparin and coumarins have been in clinical use for more than 50 years. Low-molecular-weight heparins (including a heparinoid), developed 25 years ago, have been used clinically for more than a decade.


METHODS
In the last 10 years, several new anticoagulants that target almost every step in the coagulation pathway have been developed. Of these, 3 direct thrombin inhibitors (hirudin, bivalirudin, and argatroban) are approved for clinical use. Four other anticoagulants (activated protein C, tissue factor pathway inhibitor, synthetic pentasaccharide, and the oral thrombin inhibitor H376/95) are being evaluated or have completed evaluation in phase III studies; various other compounds are in phase II studies.


RESULTS
The mechanism of action, sites of action, and potential clinical indications of these new anticoagulants are reviewed.


CONCLUSIONS
To compete effectively, the new oral anticoagulants currently under development will have to be at least as effective and safe as coumarins, oral thrombin, or Factor Xa inhibitors and require less monitoring.
Hirsh
J
J
Hamilton Civic Hospitals Research Centre and Hamilton Health Sciences Corporation, Hamilton, Ontario, Canada. jhirsh@thrombosis.hhscr.org
D000925:Anticoagulants; D000991:Antithrombins; D001777:Blood Coagulation / Q000502:physiology*; D002986:Clinical Trials as Topic; D015507:Drugs, Investigational; D006801:Humans
D000925:Anticoagulants; D000991:Antithrombins; D015507:Drugs, Investigational