Upstream Eptifibatide Treatment Linked with Better Outcomes in PCI Patients

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Patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) treated with percutaneous coronary intervention (PCI) benefit from early treatment with eptifibatide, according to a substudy of the EARLY ACS trial published online July 29, 2013, ahead of print in the American Heart Journal. However, the statistical interaction of PCI with the glycoprotein IIb/IIIa inhibitor (GPI) or medical management was inconclusive.

The overall results of EARLY ACS, published in the May 21, 2009, issue of the New England Journal of Medicine, found that early eptifibatide held no advantage over provisional use of the drug among 9,492 high-risk NSTE ACS patients slated to undergo invasive treatment at 29 centers in North America, Europe, the Middle East, Asia, and Asia-Pacific.

The substudy, led by L. Kristin Newby, MD, MHS, of Duke Clinical Research Institute (Durham, NC), looked at 9,166 patients who underwent coronary angiography plus PCI (60.5%), CABG (13.4%), medical therapy without revascularization (26.7%), or both PCI and CABG (0.5%).

GPI Lowers Death, MI Risk

Early eptifibatide compared with early placebo resulted in a reduction in the risk of 30-day death or MI (HR 0.80; 95% CI 0.68-0.95) in PCI patients, although this relationship was not seen in patients on medical management (HR 0.97; 95% CI 0.74-1.29; P for interaction = 0.24).

Treatment with PCI (vs. no PCI) was associated with less 30-day death or MI (HR 0.60; 95% CI 0.49-0.74; P < 0.0001), but routine early eptifibatide (vs. delayed provisional treatment) was not (HR 0.90; 95% CI 0.74-1.11; P = 0.34). With medical management, there was no association of early eptifibatide use with 30-day death or MI (HR 1.01; 95% CI 0.79-1.34), while with PCI, the event risk for early eptifibatide treatment was similar to that shown in the primary analysis (HR 0.80; 95% CI 0.60-1.08; P for interaction = 0.28).

Roughly one-quarter (25.8%) of patients who underwent PCI transitioned to eptifibatide after angiography but before the wire crossed the lesion (routine early eptifibatide n = 685; delayed provisional eptifibatide n = 745). For both treatment arms, risk of 30-day death or MI was higher in patients selected for transition than those who were not. Among patients randomized to early eptifibatide, those transitioned to open-label eptifibatide had a numerically higher observed event rate than those not transitioned (11.8% vs. 7.9%), whereas among patients randomized to delayed provisional eptifibatide, those who were transitioned to open-label eptifibatide and those who were not (continued on placebo) had similar observed event rates (11.4% vs. 11.2%).

A ‘Delayed Analysis’

“Routine early eptifibatide was associated with a lower rate of death or MI at 30 days with PCI treatment but not with medical management; however, the interaction between PCI and randomized treatment strategy was not statistically significant, precluding a definite conclusion that the treatment effects of routine early versus delayed provisional eptifibatide differ between PCI treatment and medical management. Provisional use of eptifibatide at the time of PCI in placebo-treated patients likely attenuated the treatment effect of early eptifibatide compared with early placebo,” Dr. Newby and colleagues write, adding that the results are in line with prior research.

Still, this is a “delayed analysis,” according to Sorin J. Brener, MD, of Weill Cornell Medical College (New York, NY). He told TCTMD in a telephone interview that “this is a subject that was studied in detail a decade ago and . . . has been abandoned for a while now.”

Since the introduction of thienopyridines, the management of ACS patients has changed, he continued. For the study to “completely [ignore] the benefits of thienopyridines or P2Y12 blockers is kind of disingenuous.”

Dr. Brener said the ACUITY trial showed no benefit with early GPI therapy and “certainly not when people are treated with 2 oral antiplatelet agents. I think it was a very valid issue prior to the strategy of using 2 antiplatelet agents, but not anymore, really. Even so, it was a very modest benefit.”

Study Details

The factors most strongly associated with PCI included presence of single-vessel disease, absence of left main disease, elevated baseline troponin, and prior CABG or PCI. Factors most strongly associated with not undergoing PCI included hypertension, time from hospitalization to randomization < 5 hours, and time from randomization to angiography < 15 hours.

 


Source:
Bagai A, White JA, Lokhnygina Y, et al. Routine early eptifibatide versus delayed provisional use at percutaneous coronary intervention in high-risk non–ST-segment elevation acute coronary syndromes patients: An analysis from the early glycoprotein IIb/IIIa inhibition in non–ST-segment elevation acute coronary syndrome trial. Am Heart J. 2013;Epub ahead of print.

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Disclosures
  • Dr. Newby reports receiving research support and consulting fees from multiple pharmaceutical companies.
  • Dr. Brener reports no relevant conflicts of interest.

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