Current developments in antithrombotic therapy: the role of antithrombin agents.

Hirudin, the specific thrombin inhibitor from medicinal leeches, is now produced by recombinant technology. r-Hirudin and to a lesser extent polyethyleneglycol-coupled hirudin (PEG-hirudin) have been used in many clinical trials. Hirudin has been shown to be more effective than low molecular weight heparin in the prevention of deep venous thrombosis after total hip replacement. In (acute) coronary syndromes hirudin as well as a synthetic hirudin analogue bivalirudin have been studied in large clinical trials. Higher doses of hirudin were associated with an increased risk of bleeding. A large-scale study with bivalirudin in patients with acute MI (the HERO-2 trial) has not shown a reduction in mortality but a 30% reduction of reinfarction within 96 h. Hirudin and argatroban have been successfully used in patients with heparin-induced thrombocytopenia type II. Several orally active thrombin inhibitors are being developed. The combined use of subcutaneous and oral administration of melagatran in patients with hip or knee replacement has led to promising results. It is likely that in the future thrombin inhibitors will replace other forms of anticoagulation in a number of indications.