title: Tenecteplase and tirofiban in ST-segment elevation acute myocardial infarction: results of a randomized trial.
abstract: BACKGROUND
  The combination of older reduced-dose fibrinolytic agents and platelet glycoprotein IIb/IIIa inhibitors has shown modest improvements in reperfusion and more striking improvements in ST-segment resolution after acute myocardial infarction. We performed a multicenter dose-ranging study of reduced doses of a newer fibrinolytic (tenecteplase) combined with tirofiban, a glycoprotein IIb/IIIa inhibitor.
  
  
  METHODS
  The first goal of the trial was to identify a dose or doses of tirofiban that, when combined with reduced-dose tenecteplase, would result in a higher incidence of Thrombolysis In Myocardial Infarction (TIMI) grade 3 flow at 60 minutes versus full-dose tenecteplase alone. The second goal was to assess whether the optimum dose(s) from the first stage also would result in greater resolution of ST-segment elevation.
  
  
  RESULTS
  In all, 409 patients aged 18 to 75 years with myocardial infarction were enrolled. The incidence of TIMI grade 3 flow at 60 minutes did not differ significantly among dose groups, ranging from 50% to 68%. The corrected TIMI frame count likewise did not differ substantially (range 34-42). More patients given combined therapy had complete resolution of ST-segment elevation at 60 minutes compared with patients given tenecteplase alone. Major bleeding was infrequent, and no strokes occurred. Based on angiographic results of the first stage, the second planned stage of the study was not performed.
  
  
  CONCLUSIONS
  Although combination therapies were not associated with increased reperfusion compared with full-dose tenecteplase alone, similar TIMI flow grades were achieved despite reductions in tenecteplase doses. ST-segment resolution was more rapid and complete with combination therapy versus full-dose tenecteplase, suggesting enhanced microcirculatory perfusion to the infarct zone in this dose-ranging trial.
authors.affiliation: Division of Cardiology, University of North Carolina, UNC Heart Center, Chapel Hill, NC, USA. mohman@med.unc.edu
authors.forename: E Magnus
authors.initials: EM
authors.lastname: Ohman
authors.forename: Frans
authors.initials: F
authors.lastname: Van de Werf
authors.forename: Elliott M
authors.initials: EM
authors.lastname: Antman
authors.forename: Robert M
authors.initials: RM
authors.lastname: Califf
authors.forename: James A
authors.initials: JA
authors.lastname: de Lemos
authors.forename: C Michael
authors.initials: CM
authors.lastname: Gibson
authors.forename: Renee L
authors.initials: RL
authors.lastname: Oliverio
authors.forename: Lynn
authors.initials: L
authors.lastname: Harrelson
authors.forename: Carolyn
authors.initials: C
authors.lastname: McCabe
authors.forename: Peter
authors.initials: P
authors.lastname: DiBattiste
authors.forename: Eugene
authors.initials: E
authors.lastname: Braunwald
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D004359:Drug Therapy, Combination; D004562:Electrocardiography; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000503:physiopathology; D000077785:Tenecteplase; D000077466:Tirofiban; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D014443:Tyrosine; D010959:Tissue Plasminogen Activator; D000077466:Tirofiban; D000077785:Tenecteplase