Antithrombin agents: The new class of anticoagulant and antithrombotic drugs

Antithrombin drugs represent a wide group of natural agents, recombinant ag ents equivalent to some of the naturally occurring proteins, and synthetic agents. This group of drugs is characterized by marked structural and funct ional heterogeneity. Several of these drugs are currently in various phases of development. Argatroban represents the first clinically approved antith rombin agent, which was made available in Japan several years ago. Two reco mbinant hirudin preparations, Revasc (Novartis) and Refludan (Aventis), are available for postsurgical DVT prophylaxis and alternate anticoagulant use in patients with heparin-induced thrombocytopenia. A synthetic antithrombi n agent based on the combined structures of hirudin and antithrombin peptid es, hirulog (Bivalirudin), is undergoing clinical trials in cardiovascular indications. Additional studies on the hirudins an being carried out to tes t their efficacy as surgical and interventional anticoagulants as replaceme nts for heparin. However, the need for a proper antagonist is one of the li miting factors for the optimal development of hirudin in this indication. S everal of the synthetic thrombin inhibitors are also being developed for or al use for the prophylaxis of DVT in surgical patients. Since the therapeut ic index of thrombin inhibitors is narrower than that of heparin, this rout e may not be an optimal approach for the development of these agents. Despi te several unresolved developmental issues, the thrombin inhibitors provide a useful alternative to heparin anticoagulation and may prove to be useful in validated clinical use.