Sequential combination thrombolytic therapy for acute myocardial infarction: results of the Pro-Urokinase and t-PA Enhancement of Thrombolysis (PATENT) Trial.

The present study was designed to test the efficacy and safety of a sequential combination of recombinant tissue-type plasminogen activator (rt-PA) and pro-urokinase in patients with acute myocardial infarction.
Efforts continue to identify a thrombolytic regimen that induces rapid, complete and sustained coronary artery patency in acute myocardial infarction. The two endogenous plasminogen activators rt-PA and pro-urokinase have been shown experimentally to induce fibrinolysis by sequential and complementary mechanisms. As a result, certain combinations of these activators have been found to be synergistic in vitro and in vivo.
In a multicenter observational study with core facilities for angiographic and laboratory analysis, 101 patients with acute myocardial infarction were enrolled and given a low dose bolus of rt-PA (5 to 10 mg) followed by a 90-min infusion of pro-urokinase (40 mg/h). All patients received intravenous heparin and oral aspirin. Coronary angiography was performed in all patients at 90 min.
Angiography at 90 min showed the infarct-related artery to be patent (Thrombolysis in Myocardial Infarction [TIMI] grade 2 or 3 flow) in 77% of patients, and 60% achieved TIMI grade 3 flow. At one center, angiography was repeated at 24 h to detect a possible reocclusion. All 28 patients with a patent infarct-related artery at 90 min had patency at 24 h (82% achieved TIMI grade 3 flow). Treatment was well tolerated, with bleeding complications essentially confined to arterial puncture site hematomas. There was only one in-hospital death.
A sequential combination of low dose rt-PA and reduced-dose pro-urokinase produced a high TIMI 3 patency rate, was well tolerated and was associated with a low reocclusion rate.
AuthorsS W Zarich, G J Kowalchuk, W D Weaver, J Loscalzo, M Sassower, K Manzo, C Byrnes, J E Muller, V Gurewich
JournalJournal of the American College of Cardiology (J Am Coll Cardiol) Vol. 26 Issue 2 Pg. 374-9 (Aug 1995) ISSN: 0735-1097 [Print] UNITED STATES
PMID7608437 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
Chemical References
  • Enzyme Precursors
  • Fibrinolytic Agents
  • Recombinant Proteins
  • saruplase
  • Tissue Plasminogen Activator
  • Urokinase-Type Plasminogen Activator
  • Adult
  • Aged
  • Confounding Factors (Epidemiology)
  • Coronary Angiography
  • Enzyme Precursors (therapeutic use)
  • Female
  • Fibrinolytic Agents (therapeutic use)
  • Humans
  • Male
  • Middle Aged
  • Myocardial Infarction (drug therapy, radiography)
  • Recombinant Proteins (therapeutic use)
  • Thrombolytic Therapy (adverse effects, methods)
  • Time Factors
  • Tissue Plasminogen Activator (therapeutic use)
  • Treatment Outcome
  • Urokinase-Type Plasminogen Activator (therapeutic use)
  • Vascular Patency (drug effects)

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