DIRECT THROMBIN INHIBITION AND THROMBOLYTIC THERAPY - RATIONALE FOR THE HIRULOG AND EARLY REPERFUSION OCCLUSION (HERO-2) TRIAL/

Worldwide, streptokinase continues to be used widely in the treatment of myocardial infarction because it is inexpensive and causes fewer in tracranial hemorrhages than other thrombolytic regimens. However, in t he Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO- I) trial, the 90-minute angiographic Thrombolysis in Myocardial Infarc tion (TIMI) trial grade 3 flow rate with streptokinase was 43% lower t han that with accelerated tissue plasminogen activator, and there was a higher incidence of death or disabling stroke with streptokinase (7. 8% vs 6.9%, p <0.01). In the first Hirulog and Early Reperfusion/Occlu sion (HERO-I) trial, 48% of patients given the direct thrombin inhibit or bivalirudin (formerly Hirulog, The Medicines Company) after strepto kinase had TIMI 3 potency at 90 minutes, compared with 35% of patients given intravenous heparin (p <0.05), Other angiographic and clinical studies and animal research have shown that early infarct artery blood flow may be increased markedly if a direct thrombin inhibitor is admi nistered before the thrombolytic agent. In the HERO-2 trial, 17,000 pa tients presenting within 6 hours after the onset of acute myocardial i nfarction will be given aspirin and randomized to receive either intra venous heparin or bivalirudin before streptokinase is administered. Th e primary endpoint will be 30-day mortality, and secondary endpoints w ill include death or myocardial infarction within 30 days, and death o r nonfatal disabling stroke. If the thrombin hypothesis is supported b y improved clinical outcomes with bivalirudin in the HERO-2 trial, lar ge-scale clinical trials will be needed to evaluate the administration of direct thrombin inhibitors before other thrombolytic regimens. (C) 1998 by Excerpta Medica, Inc.