Randomized double-blind comparison of two doses of Hirulog with heparin as adjunctive therapy to streptokinase to promote early patency of the infarct-related artery in acute myocardial infarction.
BACKGROUND
An improved survival rate is a consequence of successful reperfusion of the infarct-related artery. This double-blind, randomized trial investigated the potential of Hirulog, a direct thrombin inhibitor, to improve the early patency rates obtained with streptokinase and aspirin.


RESULTS
Angiographic patency of the culprit coronary artery lesion was assessed 90 and 120 minutes after the initiation of streptokinase and aspirin and again after 4 +/- 2 days in 68 patients with acute myocardial infarction. Patients were randomized to Hirulog 0.5 mg/kg per hour for 12 hours followed by 0.1 mg/kg per hour (low dose), Hirulog 1.0 mg/kg per hour for 12 hours followed by placebo (high dose), or to heparin 5000 U bolus followed by 1000 U/h titrated to an activated partial thromboplastin time (aPTT) 2 to 2.5 times control after 12 hours. At 90 minutes, TIMI flow grade 2 or 3 was observed in 96% of patients treated with the low dose of Hirulog, in 79% with the high dose, and in 46% with heparin (P = .006) and TIMI flow grade 3 was observed in 85%, 61%, and 31% of patients, respectively (P = .008). At 120 minutes, these figures were 100%, 82%, and 62% for TIMI flow grades 2 and 3 (P = .046) and 92%, 68%, and 46% for TIMI flow grade 3 (P = .014). At 90 minutes, the relative risk for restoring TIMI flow grade 3 was 2.77 with Hirulog 0.5 mg/kg per hour compared with heparin (95% confidence limits, 1.21 to 6.35; P < .001) and 1.4 compared with Hirulog 1.0 mg/kg per minute (95% confidence limits, 1.00 to 1.51; P = .04). Patients who received a placebo infusion after 12 hours experienced more clinical events and reocclusion during the following 4 days than patients in the other two groups.


CONCLUSIONS
Hirulog yields higher early patency rates in the culprit coronary artery than heparin when used as adjunctive therapy to streptokinase and aspirin in the early phase of acute myocardial infarction. High doses are not required and may be less effective than lower doses, which suggests that too much thrombin inhibition may be harmful.
Théroux
P
P
Department of Medicine, Montreal Heart Institute, Canada.
Pérez-Villa
F
F
Waters
D
D
Lespérance
J
J
Shabani
F
F
Bonan
R
R
D001241:Aspirin / Q000627:therapeutic use; D006328:Cardiac Catheterization; D017023:Coronary Angiography; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006493:Heparin / Q000008:administration & dosage* / Q000627:therapeutic use; D024764:Hirudin Therapy; D006629:Hirudins / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000188:drug therapy*; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D013300:Streptokinase / Q000627:therapeutic use*; D015996:Survival Rate; D013917:Thrombin / Q000037:antagonists & inhibitors*; D014654:Vascular Patency / Q000187:drug effects
D006629:Hirudins; D010446:Peptide Fragments; D011994:Recombinant Proteins; D006493:Heparin; D013300:Streptokinase; D013917:Thrombin; D001241:Aspirin; C074619:bivalirudin