RANDOMIZED, DOUBLE-BLIND COMPARISON OF HIRULOG VERSUS HEPARIN IN PATIENTS RECEIVING STREPTOKINASE AND ASPIRIN FOR ACUTE MYOCARDIAL-INFARCTION (HERO)

Background Thrombolytic therapy improves survival after myocardial inf arction through reperfusion of the infarct-related artery. Thrombin ge nerated during thrombolytic administration may reduce the efficacy of thrombolysis. A direct thrombin inhibitor may improve early patency ra tes. Methods and Results Four hundred twelve patients presenting withi n 12 hours with ST-segment elevation were given aspirin and streptokin ase and randomized in a double-blind manner to receive up to 60 hours of either heparin (5000 U bolus followed by 1000 to 1200 U/h), low-dos e hirulog (0.125 mg/kg bolus followed by 0.25 mg.kg(-1).h(-1) for 12 h ours then 0.125 mg.kg(-1).h(-1)), or high-dose hirulog (0.25 mg/kg bol us followed by 0.5 mg.kg(-1).h(-1) for 12 hours then 0.25 mg.kg(-1).h( -1)). The primary outcome was Thrombolysis In Myocardial Infarction tr ial (TIMI) grade 3 flow of the infarct-related artery at 90 to 120 min utes. TIMI 3 flow was 35% (95% CI, 28% to 44%) with heparin, 46% (95% CI, 38% to 55%) with low-dose hirulog, and 48% (95% CT, 40% to 57%) wi th high-dose hirulog (heparin versus hirulog, P = .023; heparin versus high-dose hirulog, P = .03). At 48 hours, reocclusion had occurred in 7% of heparin, 5% of low-dose hirulog, and 1% of high-dose hirulog pa tients (P=NS). By 35 days, death, cardiogenic shock, or reinfarction h ad occurred in 25 heparin (17.9%), 19 low-dose hirulog (14%), and 17 h igh-dose hirulog patients (12.5%) (P=NS). Two strokes occurred with he parin, none with low-dose hirulog, and two with high-dose hirulog. Maj or bleeding (40% from the groin site) occurred in 28% of heparin, 14% of low-dose hirulog, and 19% of high-dose hirulog patients (heparin ve rsus low-dose hirulog, P < .01). Conclusions Hirulog was more effectiv e than heparin in producing early patency in patients treated with asp irin and streptokinase without increasing the risk of major bleeding. Direct thrombin inhibition may improve clinical outcome.