Early Glycoprotein IIb/IIIa Inhibition in Non–ST-Segment Elevation Acute Coronary Syndromes - EARLY ACS


The goal of the trial was to evaluate the upstream use of the glycoprotein (GP) IIb/IIIa inhibitor eptifibatide compared with provisional eptifibatide administration in the catheterization laboratory in patients with non–ST-elevation acute coronary syndrome (NSTE ACS).


Upstream administration of a GP IIb/IIIa inhibitor would reduce major adverse cardiac events.

Study Design

Study Design:

Patients Enrolled: 9,406
Mean Follow Up: 30 days
Mean Patient Age: Median age 67 years
Female: 32%

Patient Populations:

  • Patients with NSTE ACS with at least 10 minutes of ischemic symptoms in the prior 24 hours who were undergoing early invasive therapy by the following day
  • High-risk status was defined by at least two of the following criteria:
    • ST-segment depression or transient elevation
    • Elevated creatine kinase-myocardial band or troponin
    • At least 60 years of age


  • Increased bleeding risk
  • Allergy to study medication
  • Dialysis within the last month
  • Planned use of a nonheparin anticoagulant
  • Recent use of a GP IIb/IIIa inhibitor
  • Any condition that could increase the general risk of the patient

Primary Endpoints:

  • All-cause death, MI, recurrent ischemia requiring urgent revascularization, or thrombotic bailout at 96 hours

Secondary Endpoints:

  • Death or myocardial infarction at 30 days
  • Major bleeding
  • Serious adverse events

Drug/Procedures Used:

Patients with NSTE ACS were randomized to the upstream GP IIb/IIIa inhibitor eptifibatide and 18- to 24-hour infusion (n = 4,722) versus upstream placebo and provisional eptifibatide administration after angiography (n = 4,684). Once patients were randomized, they were expected to undergo catheterization within 12-96 hours.

Concomitant Medications:

All patients received aspirin. Clopidogrel was allowed, but not required. The initial study protocol required that patients were treated with unfractionated heparin or low molecular weight heparin; however, it was ammended to allow the use of bivalirudin or fondaparinux per operator discretion.

Principal Findings:

Overall 9,406 patients were randomized. The median age was 67 years, 32% were women, 30% were diabetic, 84% had positive cardiac biomarkers, 48% had an intermediate TIMI risk score, and 35% had a high TIMI risk score. The early use of clopidogrel was intended in 75% of patients and was used at any time in 90%.

The median time from presentation to randomization was 5.6 hours, the median time of study drug infusion before percutaneous coronary intervention (PCI) was 21 hours, and 23% of the delayed group received provisional eptifibatide before PCI. The use of PCI was 59%, coronary artery bypass grafting was 13%, and medical therapy was 28%.

The primary outcome occurred in 9.3% of the upstream eptifibatide group versus 10.0% of the provisional eptifibatide group (p = 0.23). At 30 days, death or MI occurred in 11.2% versus 12.3% (p = 0.08), respectively. TIMI major bleeding was 2.6% versus 1.8% (p = 0.015), GUSTO moderate or severe bleeding was 7.6% versus 5.1% (p < 0.001), and need for transfusion was 8.6% versus 6.7% (p = 0.001), respectively.


Among patients with an NSTE ACS treated with aspirin, clopidogrel, and heparin, there was no benefit to the upstream use of eptifibatide compared with provisional use immediately prior to PCI. Routine upstream use of eptifibatide increased major bleeding as well as the need for transfusion. One-fourth of the patients in the delayed group received provisional eptifibatide.

Periprocedural bleeding is an important complication that increases patient mortality. In the current era of early routine aspirin and clopidogrel, the use of GP IIb/IIIa inhibitors for NSTE ACS is becoming increasingly selective.


Giugliano RP, White JA, Bode C, et al., on behalf of the EARLY ACS Investigators. Early versus delayed, provisional eptifibatide in acute coronary syndromes. N Engl J Med 2009;360:2176-90.

Early Glycoprotein IIb/IIIa Inhibition in Non–ST-Segment Elevation Acute Coronary Syndromes (EARLY ACS). Presented by Dr. Kristin Newby at ACC.09/i2, Orlando, FL, March 2009.

Clinical Topics: Cardiac Surgery, Congenital Heart Disease and Pediatric Cardiology, Dyslipidemia, Heart Failure and Cardiomyopathies, Pulmonary Hypertension and Venous Thromboembolism, Cardiac Surgery and CHD and Pediatrics, Cardiac Surgery and Heart Failure, Congenital Heart Disease, CHD and Pediatrics and Prevention, Lipid Metabolism, Statins, Acute Heart Failure, Pulmonary Hypertension

Keywords: Prostaglandins, Endothelins, Arterial Pressure, Thiophenes, Heart Septal Defects, Atrial, Autoimmune Diseases, Dyspnea, HIV Infections, Ductus Arteriosus, Patent, Isoxazoles, Receptors, Endothelin, Liver, Heart Failure, Hypertension, Pulmonary, Heart Septal Defects, Ventricular, Vascular Resistance, Nasopharyngitis, Sulfonamides, Connective Tissue

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