Analysis and Clinical Implications of the Synergy

The SYNERGY (Superior Yield of the New Strategy of Enoxaparin, Revascularization, and Glycoprotein IIb/IIIa Inhibitors) trial is the latest in a series of landmark studies comparing the safety and efficacy of enoxaparin to unfractionated heparin (UFH) in patients with unstable angina and non–ST-segment elevation myocardial infarction. This large, multicenter, open-label study provides important information on the use of anticoagulant therapies in the current clinical setting that promotes earlier and more aggressive interventions and the use of concomitant antiplatelet therapies. This article briefly reviews the history of major clinical trials comparing enoxaparin to UFH, in an attempt to place the rationale and study design of SYNERGY in perspective. The strengths and weaknesses of this study, in addition to the clinical implications for pharmacists and physicians, are discussed. Several factors go into the decision of which anticoagulant therapy to use, and some cardiologists are more comfortable with older, established therapies, such as UFH. Enoxaparin has important advantages over UFH in terms of ease of administration and perhaps cost. However, the bleeding risk in certain patient populations must be considered. Studies, such as SYNERGY, help to illuminate best practices for the pharmacist and clinician to help them make the most appropriate therapy choice in each particular case. (Adv Stud Pharm. 2004:12-18) A HISTORY OF ENOXAPARIN VERSUS UNFRACTIONATED HEPARIN To understand the rationale for and clinical impact of the SYNERGY (Superior Yield of the New Strategy of Enoxaparin, Revascularization, and Glycoprotein IIb/IIIa Inhibitors) trial, it is useful to briefly review the evolution of clinical data on enoxaparin versus unfractionated heparin (UFH). Two large clinical trials compared enoxaparin with UFH in the setting of predominantly conservative strategies for management of acute coronary syndrome (ACS): the ESSENCE (Efficacy and Safety of Subcutaneous Enoxaparin in Non–Q-wave Coronary Events; n = 3171) and the TIMI (Thrombolysis in Myocardial Infarction; n = 3910) 11B trials. A meta-analysis of the TIMI-IIB and ESSENCE Studies showed significant reductions with enoxaparin versus UFH in the composite endpoint of death or myocardial infarction (MI) by approximately 20% within 48 hours; this treatment benefit with enoxaparin was noted by 48 hours and through all time points through study end (day 30 and day 43, respectively). Formal recommendations for enoxaparin in the treatment of unstable angina and non–ST-segment elevation myocardial infarction (UA/NSTEMI) were then included in the updated guidelines from the American Heart Association (AHA) and the American College of Cardiology (ACC). After these initial positive results, the clinical community remained hesitant to combine enoxaparin with the emerging glycoprotein (GP) IIb/IIIa receptor antagonists. The ACUTE (Antithrombotic Combination Using Tirofiban and Enoxaparin) II trial compared treatment with enoxaparin plus GP IIb/IIIa inhibitor versus UFH plus GP IIb/IIIa inhibitor, resulting in similar outcomes and bleeding risks between the 2 treatments. The INTERACT (Integrilin and Enoxaparin Randomized Assessment of Acute Coronary Syndrome Treatment) study compared enoxaparin plus GP IIb/IIIa inhibitor plus aspirin versus UFH plus GP REVIEW