Dose-ranging study with a new two-chain rt-PA in patients with acute myocardial infarction: a multicenter trial.

Abstract

Tissue-type plasminogen activator (t-PA) derived from a melanoma cell line was first used in patients with acute myocardial infarction in the early 1980s. Recombinant DNA technology then allowed production of large amounts of t-PA. The TIMI-I trial used a two-chain recombinant (rt-PA) product. A predominantly single-chain rt-PA (alteplase) was used in the majority of the TIMI II trial. The present study used a different form of two-chain rt-PA (duteplase) to determine the effective dose for thrombolysis at 60 min, and to evaluate time to reperfusion, reocclusion at 72-96 h, coagulation profiles, and bleeding events. Duteplase was given intravenously to 75 patients a mean of 3.8 +/- 1 h after the onset of myocardial infarction. Following angiography demonstrating coronary occlusion, 23 patients received a low dose of duteplase [0.16-0.29 million international units per kilogram (MIU/kg)] over 60 min followed by a 5-h infusion in conjunction with heparin, 25 patients received a middle dose (0.30-0.41 MIU/kg) and 23 patients received a high dose (0.43-0.74 MIU/kg). Angiography was then performed every 15 min x 4. Progressive recanalization occurred over 60 min (median 45 min) with an overall success rate of 59% (mean 60-min dose: 0.37 MIU/kg). No dose-response relationship was observed. The reocclusion rate was 9% at 72-96 h. Reductions in fibrinogen and plasminogen correlated with dose, but clinical events did not.(ABSTRACT TRUNCATED AT 250 WORDS)

• Authors: M A DeWood, P B Kurnik, M K Jolly, A C Jain, F Khaja, H J Gorfinkel, D L Morris, L Satler, J LittleJohn
• Journal: Clinical cardiology (Clin Cardiol) Vol. 16 Issue 4 Pg. 302-10 (Apr 1993) ISSN: 0160-9289 [Print] United States
• PMID: 8458110 (Publication Type: Clinical Trial, Controlled Clinical Trial, Journal Article, Multicenter Study)

Chemical References

• Fibrin Fibrinogen Degradation Products
• Recombinant Proteins
• Plasminogen
• Tissue Plasminogen Activator
• duteplase

Topics

• Adult
• Aged
• Blood Coagulation (drug effects)
• Coronary Vessels (drug effects, pathology)
• Female
• Fibrin Fibrinogen Degradation Products (analysis)
• Hemorrhage (chemically induced)
• Humans
• Male
• Middle Aged
• Myocardial Infarction (blood, drug therapy, pathology)
• Plasminogen (analysis)
• Prospective Studies
• Recombinant Proteins (administration & dosage, therapeutic use)
• Recurrence
• Remission Induction
• Thrombolytic Therapy
• Time Factors
• Tissue Plasminogen Activator (administration & dosage, therapeutic use)
• Vascular Patency (drug effects)