title: Enoxaparin vs unfractionated heparin in high-risk patients with non-ST-segment elevation acute coronary syndromes managed with an intended early invasive strategy: primary results of the SYNERGY randomized trial.
abstract: BACKGROUND
  Enoxaparin has demonstrated advantages over unfractionated heparin in low- to moderate-risk patients with non-ST-segment elevation acute coronary syndromes (ACS) treated with a conservative strategy.
  
  
  OBJECTIVE
  To compare the outcomes of patients treated with enoxaparin vs unfractionated heparin and to define the role of enoxaparin in patients with non-ST-segment elevation ACS at high risk for ischemic cardiac complications managed with an early invasive approach.
  
  
  METHODS
  The Superior Yield of the New Strategy of Enoxaparin, Revascularization and Glycoprotein IIb/IIIa Inhibitors (SYNERGY) trial was a prospective, randomized, open-label, multicenter, international trial conducted between August 2001 and December 2003. A total of 10 027 high-risk patients with non-ST-segment elevation ACS to be treated with an intended early invasive strategy were recruited.
  
  
  METHODS
  Subcutaneous enoxaparin (n = 4993) or intravenous unfractionated heparin (n = 4985) was to be administered immediately after enrollment and continued until the patient required no further anticoagulation, as judged by the treating physician.
  
  
  METHODS
  The primary efficacy outcome was the composite clinical end point of all-cause death or nonfatal myocardial infarction during the first 30 days after randomization. The primary safety outcome was major bleeding or stroke.
  
  
  RESULTS
  The primary end point occurred in 14.0% (696/4993) of patients assigned to enoxaparin and 14.5% (722/4985) of patients assigned to unfractionated heparin (odds ratio [OR], 0.96; 95% confidence interval [CI], 0.86-1.06). No differences in ischemic events during percutaneous coronary intervention (PCI) were observed between enoxaparin and unfractionated heparin groups, respectively, including similar rates of abrupt closure (31/2321 [1.3%] vs 40/2364 [1.7%]), threatened abrupt closure (25/2321 [1.1%] vs 24/2363 [1.0%]), unsuccessful PCI (81/2281 [3.6%] vs 79/2328 [3.4%]), or emergency coronary artery bypass graft surgery (6/2323 [0.3%] vs 8/2363 [0.3%]). More bleeding was observed with enoxaparin, with a statistically significant increase in TIMI (Thrombolysis in Myocardial Infarction) major bleeding (9.1% vs 7.6%, P =.008) but nonsignificant excess in GUSTO (Global Utilization of Streptokinase and t-PA for Occluded Arteries) severe bleeding (2.7% vs 2.2%, P =.08) and transfusions (17.0% vs 16.0%, P =.16).
  
  
  CONCLUSIONS
  Enoxaparin was not superior to unfractionated heparin but was noninferior for the treatment of high-risk patients with non-ST-segment elevation ACS. Enoxaparin is a safe and effective alternative to unfractionated heparin and the advantages of convenience should be balanced with the modest excess of major bleeding.
authors.forename: James J
authors.initials: JJ
authors.lastname: Ferguson
authors.forename: Robert M
authors.initials: RM
authors.lastname: Califf
authors.forename: Elliott M
authors.initials: EM
authors.lastname: Antman
authors.forename: Marc
authors.initials: M
authors.lastname: Cohen
authors.forename: Cindy L
authors.initials: CL
authors.lastname: Grines
authors.forename: Shaun
authors.initials: S
authors.lastname: Goodman
authors.forename: Dean J
authors.initials: DJ
authors.lastname: Kereiakes
authors.forename: Anatoly
authors.initials: A
authors.lastname: Langer
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Mahaffey
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Nessel
authors.forename: Paul W
authors.initials: PW
authors.lastname: Armstrong
authors.forename: Alvaro
authors.initials: A
authors.lastname: Avezum
authors.forename: Phil
authors.initials: P
authors.lastname: Aylward
authors.forename: Richard C
authors.initials: RC
authors.lastname: Becker
authors.forename: Luigi
authors.initials: L
authors.lastname: Biasucci
authors.forename: Steven
authors.initials: S
authors.lastname: Borzak
authors.forename: Jacques
authors.initials: J
authors.lastname: Col
authors.forename: Marty J
authors.initials: MJ
authors.lastname: Frey
authors.forename: Ed
authors.initials: E
authors.lastname: Fry
authors.forename: Dietrich C
authors.initials: DC
authors.lastname: Gulba
authors.forename: Sema
authors.initials: S
authors.lastname: Guneri
authors.forename: Enrique
authors.initials: E
authors.lastname: Gurfinkel
authors.forename: Robert
authors.initials: R
authors.lastname: Harrington
authors.forename: Judith S
authors.initials: JS
authors.lastname: Hochman
authors.forename: Neal S
authors.initials: NS
authors.lastname: Kleiman
authors.forename: Martin B
authors.initials: MB
authors.lastname: Leon
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Lopez-Sendon
authors.forename: Carl J
authors.initials: CJ
authors.lastname: Pepine
authors.forename: Witold
authors.initials: W
authors.lastname: Ruzyllo
authors.forename: Steven R
authors.initials: SR
authors.lastname: Steinhubl
authors.forename: Paul S
authors.initials: PS
authors.lastname: Teirstein
authors.forename: Luis
authors.initials: L
authors.lastname: Toro-Figueroa
authors.forename: Harvey
authors.initials: H
authors.lastname: White
mesh_terms: D000368:Aged; D000787:Angina Pectoris / Q000188:drug therapy* / Q000401:mortality / Q000628:therapy; D015906:Angioplasty, Balloon, Coronary; D017984:Enoxaparin / Q000627:therapeutic use*; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006470:Hemorrhage / Q000453:epidemiology; D006493:Heparin / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology; D020521:Stroke / Q000453:epidemiology; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D017984:Enoxaparin; D005343:Fibrinolytic Agents; D006493:Heparin