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.
Department of Cardiology Medisch Spectrum Twente, Enschede, The Netherlands.
G P
GP
Molhoek
G J
GJ
Laarman
D J
DJ
Lok
C M
CM
Luz
J H
JH
Kingma
A A
AA
Van den Bos
P
P
Zijnen
A H
AH
Bosma
D P
DP
Hertzberger
L H
LH
Takens
D000328:Adult; D000368:Aged; D001241:Aspirin / Q000627:therapeutic use; D017023:Coronary Angiography; D004333:Drug Administration Routes; D004359:Drug Therapy, Combination; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D006493:Heparin / Q000627:therapeutic use; D006629:Hirudins / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000188:drug therapy*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D013300:Streptokinase / Q000627:therapeutic use
D005343:Fibrinolytic Agents; D006629:Hirudins; D010975:Platelet Aggregation Inhibitors; D006493:Heparin; D013300:Streptokinase; D001241:Aspirin