In patients with non–ST-elevation acute coronary syndromes (NSTE ACS), enoxaparin has been shown to be superior to unfractionated heparin (UFH) and is associated with a reduction in ischemic end points with nonsignificant increases in bleeding. However, the critical trials comparing enoxaparin with UFH were conducted before the widespread use of early invasive management and the availability of clopidogrel and glycoprotein IIb/IIIa receptor antagonists.

SYNERGY was an international, multicenter, randomized, open-label trial that compared enoxaparin with UFH in high-risk NSTE ACS patients managed with an early invasive strategy. For enrollment, 2 out of 3 high-risk features were required: age ≥60 years, elevated cardiac biomarkers, or ST-segment changes. The primary efficacy end point was death/myocardial infarction (MI) at 30 days. The primary safety end point was inhospital major bleeding or stroke through 30 days.

The incidence of death/MI at 30 days was 14.0% in the enoxaparin group and 14.5% in the UFH group (hazard ratio 0.96, 95% CI 0.86–1.06), demonstrating noninferiority of enoxaparin relative to UFH. Enoxaparin was associated with a small but significant excess of Thrombolysis In Myocardial Infarction (TIMI) major bleeding, but there was no statistically significant increase in Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) severe bleeding or the rate of transfusion. There was no difference in complications of percutaneous coronary intervention. Interpretation of trial results was complicated by widespread use of enoxaparin or UFH before randomization, and by postrandomization crossover to the nonrandomized agent.

In patients with NSTE ACS, including high-risk patients proceeding rapidly to catheterization, enoxaparin is an effective and safe alternative to UFH.