Patients do not benefit from early use of Integrilin

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ORLANDO, Fla.—In patients with high risk of MI, early utilization of eptifibatide (Integrilin) is not superior to delayed, provisional use during PCI, according to research presented Monday at the 58th annual American College of Cardiology (ACC) scientific sessions, and simultaneously published in the New England Journal of Medicine.

The EARLY ACS study (Early Glycoprotien IIb/IIIa Inhibition in Non-ST-Segment Elevation Acute Coronary Syndromes) sought to clarify the best strategy for eptifibatide (Millennium Pharmaceuticals/Schering-Plough) use, an antiplatelet drug therapy implemented in clinical practice for 10 years. The researchers examined two common strategies of eptifibatide utilization in patients with high-risk of MI: early intravenous injection upon immediate arrival at the hospital and delayed, provisional injection during PCI.

"The drivers for our study are the gaps that exist in the practice guidelines for when and how best to use eptifibatide, an already tested and proven treatment, in the context of other modern therapies that have evolved since the drug was first introduced," said L. Kristin Newby, MD, associate professor of medicine at Duke University Medical Center, Durham, N.C., who co-presented the study. "Guidelines in North America and Europe vary in their recommendations regarding early use vs. delayed provisional treatment with eptifibatide and drugs like it. Individual hospitals and individual clinicians in all regions apply these recommendations differently."

The trial was a randomized, double-blind, controlled study of early eptifibatide vs. provisional eptifibatide during PCI with standard background antithrombin therapy. The researchers enrolled 9,492 patients, all of whom were scheduled to undergo an invasive strategy 12 to 96 hours after starting the study drug.

The primary efficacy endpoint for EARLY ACS was composite all-cause death, MI and recurrent ischemia requiring urgent revascularization or thrombotic bailout during the first 96 hours. The secondary endpoint was death or MI through 30 days. The safety endpoints included bleeding, transfusions, stroke and serious adverse events.

At its final enrollment, Newby noted that EARLY ACS had a 98 percent power to detect a 22.5 percent reduction in the 96-hour primary composite with early eptifibatide versus delayed, provisional eptifibatide and 81 percent power for a 15 percent reduction in 30-day death or MI.

The researchers found that neither efficacy endpoint was the strategy of early eptifibatide use in all high-risk patients better than the delayed, provisional use of eptifibatide prior to PCI. Furthermore, early eptifibatide initiation was associated with more bleeding.

"Our study, although not the final word regarding eptifibatide, has helped shed a light on how to best use eptifibatide among high-risk patients," Newby said. "In general, physicians can feel comfortable with a strategy of delayed, provisional administration after a decision to proceed to PCI is made." As far as patients are concerned, the primary results from EARLY ACS are the key message - an early routine strategy of eptifibatide is not superior to a delayed provisional strategy."

However, Newby noted that 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 non-ST-elevation ACS patients, who are intended to undergo angiography." She added that the EARLY ACS group is currently performing analyses to further identify those subgroups, which should be released later this year.

"We have addressed an important question of clinical practice that was previously left open in our guidelines, and the decision was left up to the physician to either start now or start later. Our study shows that there are not really any benefits from starting early-and even shows the potential for bleeding risks," Newby concluded.