Efficacy of intravenous prourokinase and a combination of prourokinase and urokinase in acute myocardial infarction.
Fifty-four patients with Q-wave acute myocardial infarction (AMI) were treated with heparin combined with intravenous single-chain urokinase-type plasminogen activator (prourokinase). To determine the optimal treatment regimen, prourokinase was applied in 3 different ways: group I received a bolus of 7.5 mg and a subsequent infusion of 40.5 mg over 60 minutes. Patency of the infarct artery was observed in 7 patients (50%) at the end of the infusion time. One hour after the end of the infusion the fibrinogen level had decreased to 87 +/- 12% of the preinfusion level; the plasminogen and alpha-2 antiplasmin levels to 61 +/- 13% and 59 +/- 34%, respectively. In group II prourokinase was administered as a 7.5 mg bolus followed by 66.5 mg over 60 minutes. Eleven patients (55%) had patent infarct-related coronary arteries and fibrinogen, plasminogen and alpha-2 antiplasmin levels had decreased to 58 +/- 29%, 38 +/- 18% and 21 +/- 14%, respectively. Group III was treated with a bolus of 3.7 mg prourokinase and 250,000 IU urokinase followed by 44.3 mg prourokinase, resulting in a patency rate of 65% (13 patients). Fibrinogen, plasminogen and alpha-2 antiplasmin levels decreased to 76 +/- 15%, 67 +/- 15% and 47 +/- 29%, respectively. Fibrin-specific thrombolysis can be achieved with glycosylated prourokinase. At higher dosages considerable systemic activation of the fibrinolytic system with little enhancement of the observed therapeutic effect occurred. The combination of prourokinase and urokinase yielded a higher patency rate than either dosage of prourokinase alone, although the difference was not statistically significant in this pilot trial.
D002986:Clinical Trials as Topic; D004341:Drug Evaluation; D004359:Drug Therapy, Combination; D005260:Female; D005340:Fibrinogen / Q000032:analysis; D005343:Fibrinolytic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D006031:Glycosylation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy* / Q000628:therapy; D010865:Pilot Projects; D010958:Plasminogen / Q000032:analysis; D010960:Plasminogen Activators / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D013997:Time Factors; D014568:Urokinase-Type Plasminogen Activator / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D014654:Vascular Patency / Q000187:drug effects; D000979:alpha-2-Antiplasmin / Q000032:analysis
D005343:Fibrinolytic Agents; D000979:alpha-2-Antiplasmin; D005340:Fibrinogen; D010958:Plasminogen; D010960:Plasminogen Activators; D014568:Urokinase-Type Plasminogen Activator