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.
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.
Ferguson
James J
JJ
Califf
Robert M
RM
Antman
Elliott M
EM
Cohen
Marc
M
Grines
Cindy L
CL
Goodman
Shaun
S
Kereiakes
Dean J
DJ
Langer
Anatoly
A
Mahaffey
Kenneth W
KW
Nessel
Christopher C
CC
Armstrong
Paul W
PW
Avezum
Alvaro
A
Aylward
Phil
P
Becker
Richard C
RC
Biasucci
Luigi
L
Borzak
Steven
S
Col
Jacques
J
Frey
Marty J
MJ
Fry
Ed
E
Gulba
Dietrich C
DC
Guneri
Sema
S
Gurfinkel
Enrique
E
Harrington
Robert
R
Hochman
Judith S
JS
Kleiman
Neal S
NS
Leon
Martin B
MB
Lopez-Sendon
Jose Luis
JL
Pepine
Carl J
CJ
Ruzyllo
Witold
W
Steinhubl
Steven R
SR
Teirstein
Paul S
PS
Toro-Figueroa
Luis
L
White
Harvey
H
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
D017984:Enoxaparin; D005343:Fibrinolytic Agents; D006493:Heparin