title: Streptokinase and enoxaparin as an alternative to fibrin-specific lytic-based regimens: an ExTRACT-TIMI 25 analysis.
abstract: BACKGROUND
  Enoxaparin was superior to unfractionated heparin (UFH), regardless of fibrinolytic agent in ST-elevation myocardial infarction (STEMI) patients receiving fibrinolytic therapy in ExTRACT-TIMI 25 (Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction Treatment - Thrombolysis in Myocardial Infarction 25) trial.
  
  
  OBJECTIVE
  This post hoc analysis compared outcomes with streptokinase plus enoxaparin to the standard regimen of fibrin-specific lytic (FSL) plus UFH and to the newer combination of FSL plus enoxaparin.
  
  
  METHODS
  In ExTRACT-TIMI 25, STEMI patients received either streptokinase or a FSL (alteplase, reteplase or tenecteplase) at the physician's discretion and were randomized to enoxaparin or UFH, stratified by fibrinolytic type. Thirty-day outcomes were adjusted for baseline characteristics, region, in-hospital percutaneous coronary intervention (PCI) and a propensity score for the choice of lytic.
  
  
  RESULTS
  The primary trial endpoint of 30-day death/myocardial infarction (MI) occurred in fewer patients in the streptokinase-enoxaparin cohort (n = 2083) compared with FSL-UFH (n = 8141) [10.2% vs 12.0%, adjusted odds ratio [OR(adj)] 0.76; 95% CI 0.62, 0.93; p = 0.008]. Major bleeding was significantly increased with streptokinase-enoxaparin compared with FSL-UFH (OR(adj) 2.74; 95% CI 1.81; 4.14; p < 0.001) but intracranial haemorrhage (ICH) was similar (OR(adj) 0.90; 95% CI 0.40, 2.01; p = 0.79). Net clinical outcomes, defined as either death/MI/major bleeding or as death/MI/ICH tended to favour streptokinase-enoxaparin compared with FSL-UFH (OR(adj) 0.88; 95% CI 0.73, 1.06; p = 0.17; and OR(adj) 0.77; 95% CI 0.63, 0.93; p = 0.008, respectively). Patients receiving FSL-enoxaparin (n = 8142) and streptokinase-enoxaparin therapies experienced similar adjusted rates of the primary endpoint (OR(adj) 1.08; 95% CI 0.87, 1.32; p = 0.49) and net clinical outcomes.
  
  
  CONCLUSIONS
  Our results suggest that fibrinolytic therapy with the combination of streptokinase and the potent anticoagulant agent enoxaparin resulted in similar adjusted outcomes compared with more costly regimens utilizing a FSL.
authors.affiliation: TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Roberto R
authors.initials: RR
authors.lastname: Giraldez
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Wiviott
authors.forename: Jose C
authors.initials: JC
authors.lastname: Nicolau
authors.forename: Satishkumar
authors.initials: S
authors.lastname: Mohanavelu
authors.forename: David A
authors.initials: DA
authors.lastname: Morrow
authors.forename: Elliott M
authors.initials: EM
authors.lastname: Antman
authors.forename: Robert P
authors.initials: RP
authors.lastname: Giugliano
mesh_terms: D000328:Adult; D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D023381:Endpoint Determination; D017984:Enoxaparin / Q000627:therapeutic use*; D005260:Female; D005337:Fibrin / Q000187:drug effects*; D005343:Fibrinolytic Agents / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D006470:Hemorrhage / Q000139:chemically induced / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000401:mortality / Q000517:prevention & control; D010960:Plasminogen Activators / Q000191:economics / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000627:therapeutic use; D013300:Streptokinase / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D000077785:Tenecteplase; D015912:Thrombolytic Therapy; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000191:economics / Q000627:therapeutic use; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D017984:Enoxaparin; D005343:Fibrinolytic Agents; D011994:Recombinant Proteins; D005337:Fibrin; C087896:reteplase; D013300:Streptokinase; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator; D000077785:Tenecteplase