Randomized, double-blind comparison of hirulog versus heparin in patients receiving streptokinase and aspirin for acute myocardial infarction (HERO). Hirulog Early Reperfusion/Occlusion (HERO) Trial Investigators.
BACKGROUND
Thrombolytic therapy improves survival after myocardial infarction through reperfusion of the infarct-related artery. Thrombin generated during thrombolytic administration may reduce the efficacy of thrombolysis. A direct thrombin inhibitor may improve early patency rates.


RESULTS
Four hundred twelve patients presenting within 12 hours with ST-segment elevation were given aspirin and streptokinase 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-dose hirulog (0.125 mg/kg bolus followed by 0.25 mg x kg(-1) x h(-1) for 12 hours then 0.125 mg x kg(-1) x h(-1)), or high-dose hirulog (0.25 mg/kg bolus followed by 0.5 mg x kg(-1) x h(-1) for 12 hours then 0.25 mg x kg(-1) x h(-1)). The primary outcome was Thrombolysis In Myocardial Infarction trial (TIMI) grade 3 flow of the infarct-related artery at 90 to 120 minutes. 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% CI, 40% to 57%) with 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 patients (P=NS). By 35 days, death, cardiogenic shock, or reinfarction had occurred in 25 heparin (17.9%), 19 low-dose hirulog (14%), and 17 high-dose hirulog patients (12.5%) (P=NS). Two strokes occurred with heparin, none with low-dose hirulog, and two with high-dose hirulog. Major bleeding (40% from the groin site) occurred in 28% of heparin, 14% of low-dose hirulog, and 19% of high-dose hirulog patients (heparin versus low-dose hirulog, P<.01).


CONCLUSIONS
Hirulog was more effective than heparin in producing early patency in patients treated with aspirin and streptokinase without increasing the risk of major bleeding. Direct thrombin inhibition may improve clinical outcome.
White
H D
HD
Green Lane Hospital, Auckland, New Zealand. white002@msn.com
Aylward
P E
PE
Frey
M J
MJ
Adgey
A A
AA
Nair
R
R
Hillis
W S
WS
Shalev
Y
Y
Brown
M A
MA
French
J K
JK
Collins
R
R
Maraganore
J
J
Adelman
B
B
D000704:Analysis of Variance; D000991:Antithrombins / Q000009:adverse effects / Q000627:therapeutic use*; D001241:Aspirin / Q000627:therapeutic use*; D006328:Cardiac Catheterization; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006493:Heparin / Q000009:adverse effects / Q000627:therapeutic use*; D024764:Hirudin Therapy; D006629:Hirudins / Q000009:adverse effects / Q000031:analogs & derivatives*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy*; D010446:Peptide Fragments / Q000009:adverse effects / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D012008:Recurrence; D013300:Streptokinase / Q000627:therapeutic use*; D015912:Thrombolytic Therapy
D000991:Antithrombins; D006629:Hirudins; D010446:Peptide Fragments; D011994:Recombinant Proteins; D006493:Heparin; D013300:Streptokinase; D001241:Aspirin; C074619:bivalirudin