Angiographic dose-finding study with r-hirudin (HBW 023) for the improvement of thrombolytic therapy with streptokinase (HIT-SK) Interim results

To evaluate the efficacy and safety of hirudin, a direct thrombin inhibitor, in patients with acute myocardial infarction, a dose-finding, angiography study was carried out. After a pilot phase in 10 patients treated with a bolus of 0.1 mg.kg-1 and a continuous infusion of 0.06 mg.kg-1.h-1 (dose group I), two doses of hirudin, bolus 0.2 mg.kg-1.h-1 (DG II), and bolus 0.4 mg.kg-1 with 0.15 mg.kg-1.h-1 (DG III) were tested and compared with heparin as an adjunct to streptokinase and aspirin. This interim analysis was mandatory due to puncture-site related bleedings. Early and complete patency was achieved in 30% of 35 heparin patients, in 40% of 10 DG I, in 47% of 58 DG II and in 62% of 14 DG III patients. A dose-response relationship particularly between DG I and DG II, was also observed in the anti-thrombotic activity monitored by the aPTT. Apart from the catheter-related bleedings, there were low rates of serious adverse events.