• Myocardial Infarction Clinical Trials

The early routine administration of eptifibatide is not superior to delayed provisional eptifibatide use among invasively managed patients with high-risk non-ST- segment elevation acute coronary syndrome (NSTE ACS), according to findings from the Early Glycoprotein IIb/IIIa Inhibition in Non-ST-Segment Elevation Acute Coronary Syndromes (EARLY-ACS; NCT00089895) study. Moreover, compared with delayed use, early eptifibatide use increases bleeding and transfusion rates.

L. Kristin Newby, MD, MHS, Duke University Medical Center, Durham, NC, and Robert P. Giugliano, MD, SM, Brigham and Women's Hospital, Boston, MA, reported findings from the EARLY-ACS trial, which was designed to compare a strategy of eptifibatide that was initiated shortly after presentation with a strategy of delayed provisional use of the glycoprotein IIb/IIIa inhibitor just prior to percutaneous coronary intervention (PCI).

The EARLY-ACS trial included 9492 patients with 2 or more high-risk criteria, including an age of 60 years or older, elevated troponin or creatine kinase MB, and ischemic changes on electrocardiography. Within 12 hours of presentation, patients were randomly assigned to treatment with a strategy of early, routine eptifibatide administration shortly after presentation (n=4722) or a strategy of delayed, provisional eptifibatide use at the treating physician's discretion after coronary angiography and prior to PCI (n=4684). The primary endpoint was a composite of death, myocardial infarction (MI), recurrent ischemia that required urgent revascularization, and thrombotic bailout within 96 hours of treatment.

The primary endpoint occurred in 9.3% of patients in the early eptifibatide group and 10.0% of those in the delayed eptifibatide group (OR, 0.92; 95% CI, 0.80 to 1.06; p=0.23). There was a nonsignificant trend toward a reduction in the risk of death or MI at 30 days with early versus delayed eptifibatide treatment (11.2% vs 12.3%; OR, 0.89; 95% CI, 0.79 to 1.01; p=0.08), but there was no difference between these groups in the 30-day mortality rate (2.8% vs 2.6%; p=0.46).

The early eptifibatide strategy increased bleeding risk through 120 hours, as measured by Thrombolysis in Myocardial Infarction (TIMI) and Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) criteria. Compared with those in the delayed eptifibatide group, patients in the early eptifibatide group had a higher rate of TIMI major hemorrhage (1.8% vs 2.6%; p=0.02), TIMI major or minor bleeding (3.4% vs 5.8%; p<0.001), GUSTO moderate or severe bleeding (5.1% vs 7.6%; p<0.001), and red blood cell transfusion (6.7% vs 8.6%; p=0.001). However, there were no significant differences in the risks of life-threatening bleeding (GUSTO severe bleeding 0.8% vs 0.9%; p=0.97), peri-CABG bleeding, thrombocytopenia, or stroke between the early-routine and delayed-provision eptifibatide groups.

These findings do not support the routine use of early eptifibatide in patients with high-risk NSTE ACS that is managed with an invasive strategy. However, if subgroups of patients with high likelihood of benefit and low bleeding risk could be identified, it might be reasonable to consider early eptifibatide use in selected high-risk NSTE ACS patients who intend to undergo angiography, Dr. Giugliano said.

EARLY ACS joins an array of other trials—including PURSUIT, PRISM, PARAGON A, PARAGON B, ACUITY, and ACUITY Timing—that have examined the utility and timing of small molecule glycoprotein IIb/IIIa inhibition in NSTE ACS. Together, these trials suggest a role for glycoprotein IIb/IIIa inhibition in the management of selected high-risk patients. Future analyses may identify which subgroups of patients are most likely to benefit.

Findings from the EARLY-ACS trial were simultaneously published online in the New England Journal of Medicine.

• © 2009 MD Conference Express