New antithrombotics in the prevention of thromboembolic disease.

New anticoagulants are under development to improve on current ones that, although effective, have limitations in efficacy, safety and convenience. We have reviewed the use of these agents as thromboprophylactic drugs. These new agents have more specific modes of action and can be divided into three groups. Inhibitors of the initiation of coagulation work via inhibition of the factor VIIa/tissue factor complex. Inhibitors of propagation of coagulation include parenteral and oral factor Xa inhibitors, factor IXa inhibitors, inhibitors of factor Va and VIIIa, activated Protein C, soluble thrombomodulin and SNAC-Heparin. Finally, direct inhibitors of thrombin are under development both for parenteral and oral administration. Several new drugs, such as fondaparinux, hirudin, argatroban, bivalirudin and ximelagatran, have already been licensed for specific indications and are being investigated for more general usage. Other drugs reviewed are in much earlier stages of development.