Hirudin: initial results in acute myocardial infarction, unstable angina and angioplasty.

The central role of thrombosis in the pathogenesis of acute myocardial infarction, unstable angina and complications after angioplasty has led to intense interest in developing more effective antithrombotic agents for these disorders. Hirudin, a direct thrombin inhibitor, has undergone extensive testing in experimental models and has recently been evaluated in patients in several pilot trials. Across these three indications, hirudin has been found to achieve a more consistent level of anticoagulation than heparin, as gauged by the activated parital thromboplastin time. Similarly, as an adjunct to thrombolytic therapy in acute myocardial infarction, in the treatment of unstable angina and in support of angioplasty, hirudin appeared to improve indexes of coronary reperfusion and patency. Initial results with clinical end points, including death or myocardial infarction, appeared to favor hirudin over heparin. In several large phase III trials, hirudin is being compared with heparin for all three indications. In the first phases of these trials, the rate of hemorrhagic events, including intracranial hemorrhage, was higher than expected in both the hirudin and heparin arms, which demonstrated that a safety ceiling had been reached. The reformulated Thrombolysis in Myocardial Infarction (TIMI) 9 and Second Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO II) trials are using lower doses of hirudin and heparin, which should allow testing of whether the initial favorable results observed in pilot trials will translate into improved clinical outcome, with an acceptable safety profile, for patients with acute myocardial infarction or unstable angina or those undergoing angioplasty.