title: Efegatran sulfate as an adjunct to streptokinase versus heparin as an adjunct to tissue plasminogen activator in patients with acute myocardial infarction. ESCALAT Investigators.
abstract: BACKGROUND
  Previous clinical studies have shown that direct antithrombins can accelerate clot lysis after treatment with streptokinase in acute myocardial infarction (MI). Efegatran is a new direct antithrombin, which in experimental animals has been shown to enhance thrombolysis, reduce rate of reocclusion, and limit infarct size. This study was designed to compare the efficacy of efegatran plus streptokinase versus heparin plus accelerated tissue plasminogen activator (TPA) in coronary reperfusion in acute MI.
  
  
  RESULTS
  In this randomized, dose-finding study (n = 245), we initially explored 4 doses of efegatran sulfate in combination with streptokinase (1.5 million U) given intravenously within 12 hours of symptom onset. The optimal dosage group of 0.5 mg/kg per hour was expanded and compared with heparin plus accelerated TPA. The primary end point was complete patency (Thrombolysis In Myocardial Infarction [TIMI] grade 3) at 90 minutes after thrombolytic therapy, assessed in a core angiographic laboratory. Infarct-related vessel patency (TIMI grade 2 or 3) and complete patency (TIMI grade 3) were 73% and 40% in the efegatran/streptokinase group versus 79% and 53% in the heparin/TPA group (P = not significant). In-hospital mortality rate was 5% for the efegatran/streptokinase group versus 0% for the heparin/TPA group (P = not significant). Major bleeding occurred in 23% of patients in the efegatran/streptokinase group versus 11% in the heparin/TPA group (P = not significant). No intracranial hemorrhage occurred.
  
  
  CONCLUSIONS
  The combination of efegatran plus streptokinase is not superior to the current therapy of heparin and accelerated TPA in achieving early patency. In addition, there is no indication that this experimental treatment can achieve better clinical outcome.
authors.affiliation: Division of Cardiology, University of British Columbia, Valley Medical Center, Canada. funga@interchange.ubc.ca
authors.forename: A Y
authors.initials: AY
authors.lastname: Fung
authors.forename: G
authors.initials: G
authors.lastname: Lorch
authors.forename: P A
authors.initials: PA
authors.lastname: Cambier
authors.forename: D
authors.initials: D
authors.lastname: Hansen
authors.forename: B G
authors.initials: BG
authors.lastname: Titus
authors.forename: J S
authors.initials: JS
authors.lastname: Martin
authors.forename: J J
authors.initials: JJ
authors.lastname: Lee
authors.forename: N R
authors.initials: NR
authors.lastname: Every
authors.forename: A P
authors.initials: AP
authors.lastname: Hallstrom
authors.forename: D
authors.initials: D
authors.lastname: Stock-Novack
authors.forename: J
authors.initials: J
authors.lastname: Scherer
authors.forename: W D
authors.initials: WD
authors.lastname: Weaver
mesh_terms: D000991:Antithrombins / Q000008:administration & dosage / Q000627:therapeutic use*; D006328:Cardiac Catheterization; D017023:Coronary Angiography; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D006493:Heparin / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy*; D009842:Oligopeptides / Q000008:administration & dosage / Q000627:therapeutic use*; D013300:Streptokinase / Q000008:administration & dosage / Q000627:therapeutic use*; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000627:therapeutic use*; D014654:Vascular Patency / Q000187:drug effects
chemical_list: D000991:Antithrombins; D005343:Fibrinolytic Agents; D009842:Oligopeptides; D006493:Heparin; D013300:Streptokinase; D010959:Tissue Plasminogen Activator; C064289:efegatran