Antithrombin drugs represent a wide group of natural agents, recombinant agents equivalent to some of the naturally occurring
proteins, and synthetic agents. This group of drugs is characterized by marked structural and functional heterogeneity. Several of these drugs are currently in various phases of development.
Argatroban represents the first clinically approved
antithrombin agent, which was made available in Japan several years ago. Two recombinant
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
antithrombin agent based on the combined structures of
hirudin and
antithrombin peptides,
hirulog (
Bivalirudin), is undergoing clinical trials in cardiovascular indications. Additional studies on the
hirudins are being carried out to test their efficacy as surgical and interventional
anticoagulants as replacements for
heparin. However, the need for a proper antagonist is one of the limiting factors for the optimal development of
hirudin in this indication. Several of the synthetic
thrombin inhibitors are also being developed for oral use for the prophylaxis of DVT in surgical patients. Since the therapeutic index of
thrombin inhibitors is narrower than that of
heparin, this route may not be an optimal approach for the development of these agents. Despite several unresolved developmental issues, the
thrombin inhibitors provide a useful alternative to
heparin anticoagulation and may prove to be useful in validated clinical use.