Clot-selective coronary thrombolysis with low-dose synergistic combinations of single-chain urokinase-type plasminogen activator and recombinant tissue-type plasminogen activator. The Pro-Urokinase for Myocardial Infarction Study Group.

Abstract

The effect of simultaneous infusions of low-dose recombinant tissue-type plasminogen activator (t-PA) and single-chain urokinase-type plasminogen activator (scu-PA, pro-urokinase) on coronary arterial thrombolysis was investigated in 23 patients treated within 6 hours (mean 2.6 +/- 1.1, range 1.2 to 5.9) of symptoms of an acute myocardial infarction. Infarct artery patency at 90 minutes was achieved in 16 (70%, 95% confidence limits of 0.47 to 0.87) of 23 patients after a 1-hour intravenous infusion of 20 and 16.3 mg of t-PA and scu-PA, respectively. At 90 minutes, the fibrinogen concentration decreased from 369 +/- 207 to 316 +/- 192 mg/dl (p = not significant), while plasminogen decreased to 69 +/- 24% (p = 0.001) and alpha-2-antiplasmin to 77 +/- 24% (p = 0.001) of pretreatment values. Although no bleeding requiring termination of drug infusion or transfusion occurred, 1 patient with cerebrovascular amyloidosis had a fatal intracerebral hemorrhage. These findings suggest that combination therapy may allow substantial reductions in total thrombolytic doses while still achieving effective fibrin-specific coronary thrombolysis.

• Authors: J M Kirshenbaum, R D Bahr, J T Flaherty, V Gurewich, H J Levine, J Loscalzo, R R Schumacher, E J Topol, D W Wahr, E Braunwald
• Journal: The American journal of cardiology (Am J Cardiol) Vol. 68 Issue 17 Pg. 1564-9 (Dec 15 1991) ISSN: 0002-9149 [Print] United States
• PMID: 1746455 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Drug Combinations
• Fibrin Fibrinogen Degradation Products
• Recombinant Proteins
• Fibrinogen
• Tissue Plasminogen Activator
• Urokinase-Type Plasminogen Activator

Topics

• Adult
• Aged
• Coronary Angiography
• Coronary Thrombosis (drug therapy, pathology)
• Drug Combinations
• Female
• Fibrin Fibrinogen Degradation Products (analysis)
• Fibrinogen (analysis)
• Humans
• Infusions, Intravenous
• Injections, Intravenous
• Male
• Middle Aged
• Myocardial Infarction (drug therapy, pathology)
• Prospective Studies
• Recombinant Proteins
• Thrombolytic Therapy (methods)
• Time Factors
• Tissue Plasminogen Activator (administration & dosage, adverse effects, therapeutic use)
• Urokinase-Type Plasminogen Activator (administration & dosage, adverse effects, therapeutic use)
• Vascular Patency (drug effects)