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A Prospective, Randomized Trial of Enoxaparin and Unfractionated Heparin in Patients With Acute Coronary Syndromes - Results in Patients Undergoing Percutaneous Coronary Intervention - SYNERGY-PCI
Description:
The goal of this substudy of patients undergoing PCI in the SYNERGY trial was to evaluate the safety and efficacy of enoxaparin compared with unfractionated heparin (UFH) in high-risk patients with non-ST-segment elevation acute coronary syndromes (ACSs).
Hypothesis:
In patients undergoing PCI, treatment with enoxaparin will be associated with a reduction in death or nonfatal myocardial infarction (MI) at 30 days compared with UFH in high-risk patients with non-ST-segment elevation ACS
Study Design
Study Design:
Patients Enrolled: 4687
Mean Follow Up: 1 year
Patient Populations:
Age >18 years; ischemic pain at rest lasting >10 minutes and occurring within 24 hours before enrollment; and at least two of the following: electrocardiographic changes, age >60 years, and abnormal cardiac markers within 24 hours before enrollment
Exclusions:
Known or suspected to be pregnant; allergic to pork or pork products; contraindications to UFH or low molecular weight heparin; or recent (<48 hours) or planned spinal or epidural anesthesia or puncture, PCI within the past 24 hours, or thrombolytic therapy within the preceding 24 hours; ischemic stroke within the last year or any previous hemorrhagic stroke, tumor, or intracranial aneurysm; recent trauma or major surgery (including bypass surgery); active bleeding; impaired hemostasis caused by known international normalized ratio >1.5; a past or present bleeding disorder; thrombocytopenia; history of thrombocytopenia with GP IIb/IIIa inhibitor therapy, heparin, or enoxaparin; angina from a secondary cause; anemia; valvular disease; congenital heart disease; hypertrophic cardiomyopathy; restrictive or constrictive cardiomyopathy; thyrotoxicosis; other serious comorbidities; treatment within 30 days or planned use of other investigational agents or devices; previous enrollment in this trial; inability to give informed consent; contraindications to coronary angiography or PCI; and high likelihood of being unavailable for follow-up
Primary Endpoints:
Efficacy: Death or nonfatal MI at 30 days
Safety: Major bleeding and stroke
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.
Secondary Endpoints:
Combined incidence of all-cause mortality, nonfatal MI, stroke, or recurrent ischemia requiring revascularization and individual components of the composite at 14 days and 30 days; the incidence of death or nonfatal MI at 14 days and six months; and mortality at one year
Drug/Procedures Used:
Patients were randomized in an open-label manner to enoxaparin (subcutaneously 1 mg/kg every 12 hours) or UFH (bolus of 60 U/kg and initial infusion of 12 U/kg/h, activated partial thromboplastin time goal 1.5-2.0 times upper limit of normal). Randomized treatment was started immediately after enrollment and continued at least through angiography and percutaneous coronary intervention (PCI) and until the patient required no further anticoagulation
Concomitant Medications:
Aspirin (162 mg to 325 mg). Glycoprotein (GP) IIb/IIIa inhibitors at the physician's discretion in patients at high risk and during PCI.
Principal Findings:
PCI was performed in 4687 of the 9978 patients enrolled in SYNERGY. 46% of the patients in the enoxaparin arm (n=2364)and 47% of patients in the UFH arm (n=2323) underwent PCI. The median time to PCI was 23 hrs for both groups undergoing PCI and treatment times for initiation of the study medications were similar. No statistically significant difference in the combined endpoint of death or myocardial infarction (13.5% enoxaparin v. 14.7 UFH; p=0.23) was found when the enoxaparin and UFH groups. There were increased rates of TIMI major bleeding in patients undergoing PCI who received enoxaparin. Subsequent analysis revealed that bleeding were increased in patients who crossed over from inital treatment with UFH to enoxaparin (7.8% v. 3.1%) or vice versa (8.6% v. 2.4%). Likewise, transfusion requirements were increased among patients who crossed over from initial therapy (18.6% v. 5% for inital therapy with enoxaparin and 13.6% v. 5.7% for initial therapy with UFH).
Interpretation:
Among moderate to high risk undergoing PCI, the results of this PCI substudy parallel those of the main SYNERGY study; the use of enoxaparin is statistically not inferior to treatment with unfractionated heparin. Bleeding complications were increased in patients treated with enoxaparin, particularly those receiving both UFH and enoxaparin during their course of treatment. The effect of increased usage of Glycoprotein IIb/IIIa receptor antagonists on these results is unknown.
References:
Kleiman, N. Prospective Randomized Trial of Enoxaparin and Unfractionated Heparin in Patients with Acute Coronary Syndromes-Results in Patients Undergoing Percutaneous Coronary Intervention. Presented at Transcatheter Therapeutics 2004, Sept. 27.
Keywords: Myocardial Infarction, Acute Coronary Syndrome, Pyridinolcarbamate, Enoxaparin, Partial Thromboplastin Time, Heparin, Percutaneous Coronary Intervention, Platelet Glycoprotein GPIIb-IIIa Complex
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