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

• Published in: JAMA : the journal of the American Medical Association Vol. 292; no. 1; pp. 45 - 54
• Main Authors: Ferguson, James J, Califf, Robert M, Antman, Elliott M, Cohen, Marc, Grines, Cindy L, Goodman, Shaun, Kereiakes, Dean J, Langer, Anatoly, Mahaffey, Kenneth W, Nessel, Christopher C, Armstrong, Paul W, Avezum, Alvaro, Aylward, Phil, Becker, Richard C, Biasucci, Luigi, Borzak, Steven, Col, Jacques, Frey, Marty J, Fry, Ed, Gulba, Dietrich C, Guneri, Sema, Gurfinkel, Enrique, Harrington, Robert, Hochman, Judith S, Kleiman, Neal S, Leon, Martin B, Lopez-Sendon, Jose Luis, Pepine, Carl J, Ruzyllo, Witold, Steinhubl, Steven R, Teirstein, Paul S, Toro-Figueroa, Luis, White, Harvey
• Format: Journal Article
• Language: English
• Published: Chicago, IL American Medical Association 07.07.2004
• Subjects: Aged; Angina Pectoris - drug therapy; Angina Pectoris - mortality; Angina Pectoris - therapy; Angioplasty, Balloon, Coronary; Biological and medical sciences; Cardiology. Vascular system; Cardiovascular disease; Clinical outcomes; Clinical trials; Coronary heart disease; Enoxaparin - therapeutic use; Female; Fibrinolytic Agents - therapeutic use; General aspects; Heart; Hemorrhage - epidemiology; Heparin - therapeutic use; Humans; Male; Medical sciences; Medical treatment; Middle Aged; Myocardial Infarction - epidemiology; Stroke - epidemiology; Survival Analysis; Treatment Outcome; Human; High risk; Acute; Cardiovascular disease; Low molecular weight heparin; Anticoagulant; Coronary heart disease; Enoxaparin sodium; Medicine; ST elevation; Primitive; Risk factor; Primary; Clinical trial; Early; Strategy; Comparative study
• ISSN: 0098-7484; 1538-3598
• DOI: 10.1001/jama.292.1.45

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 recruited. 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 physician. 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.