Context 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.
Objectives 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.
Design, Setting, and Participants 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
Interventions 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
Main Outcome Measures 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.