[Direct inhibition of thrombin. A new strategy for the treatment of atrial fibrillation and acute coronary syndrome?].

Direct inhibition of thrombin is a promising new strategy for the treatment of cardiovascular disease and thrombosis. Three intravenous (lepirudin, bivalirudin and argatroban) and one oral direct thrombin inhibitor (ximelagatran) are currently available and approved for some clinical indications in the treatment of cardiovascular disease and venous thrombosis. Further indications are under investigation in large clinical trials. The bivalent direct thrombin inhibitor (DTI) lepirudin is used for anticoagulation of patients with heparin-induced thrombocytopenia (HIT) as is the monovalent DTI argatroban. The bivalent DTI bivalirudin has been studied extensively in the REPLACE 1 and 2 trials. Results from these studies demonstrate that bivalirudin is as effective as heparin for patients undergoing percutaneous coronary intervention (PCI) and leads to less bleeding complications. Efficacy and safety of anticoagulation with bivalirudin in patients with unstable angina or non-ST elevation myocardial infarction (NSTEMI) are currently under investigation in the ACUITY trial. A fixed dose of 36 mg twice daily ximelagatran, an oral prodrug of melagatran, has been shown to be safe and as effective as warfarin for the treatment of patients with nonvalvular atrial fibrillation in the SPORTIF III and V trials. This review focuses on the pharmacology of the DTIs and discusses the results of major clinical trials with DTIs in nonvalvular atrial fibrillation and acute coronary syndromes.