ACCOAST-PCI: Prasugrel treatment should be deferred for non-STEMI
Pretreatment with prasugrel was not associated with decreased ischemic events compared with placebo in patients with non-STEMI, according to results of the ACCOAST-PCI study.
The data were first reported at EuroPCR 2014 and are now published in the Journal of the American College of Cardiology.
The randomized, double blind trial included 4,033 patients with non-STEMI, 68.7% of whom underwent PCI. Half of those patients received pretreatment with prasugrel (Effient, Eli Lilly/Daiichi Sankyo) as a 30-mg loading dose (n=1,394) and the other half received placebo (n=1,376). Patients in the pretreatment group also received an additional 30 mg of prasugrel at the time of PCI, and patients in the placebo group received a 60-mg loading dose of prasugrel.
A composite of CV death, MI, stroke, urgent revascularization or glycoprotein IIb/IIIa bailout through 7 days from randomization served as the primary endpoint.
At 7 days after randomization, the primary endpoint was reported in 13.1% of patients assigned prasugrel pretreatment and 13.1% of patients assigned placebo (P=.93). At 30 days, this outcome was reported in 14.1% and 13.8%, respectively (P=.77). Pretreatment also failed to decrease overall mortality (7 days: 0.29% vs. 0.29%; 30 days: 0.79% vs. 0.8%), the incidence of the main secondary endpoint of CV death, MI or stroke (7 days: 8.5% vs. 8.4%; 30 days: 9.2% vs. 8.8%) and stent thrombosis (7 days: 0.07% vs. 0.22%; 30 days: 0.14% vs. 0.36%).
The incidence of the primary endpoint at 7 and 30 days was threefold higher in patients with thrombus on angiography compared with patients without thrombus. Multivariate analysis indicated that the presence of thrombus on angiography was predictive of the primary efficacy outcome (HR=2.61; 95% CI, 2.09-3.25) after adjustment. Other significant predictors were length of procedure (HR=1.88; 95% CI, 1.49-2.36), maximum length of stent (HR=1.19; 95% CI, 1.04-1.35), lesion number (HR=1.24; 95% CI, 1.1-1.39) and CRUSADE risk score (HR=1.01; 95% CI, 1-1.02).
Five percent of patients required bailout use of glycoprotein IIb/IIIa inhibitors, at a similar rate between the pretreatment and placebo groups.
The researchers observed a threefold increase in all non-CABG TIMI major bleeding in the pretreatment group (1.4% vs. 0.51%; HR=2.69; 95% CI, 1.13-6.4). Additionally, non-CABG life-threatening bleeding was six times more likely in patients assigned pretreatment (0.86% vs. 0.15%; HR=5.93; 95% CI, 1.33-26.5). These increases were observed in patients who underwent procedures using radial and femoral access, as well as those in whom a closure device was used.
“In patients with non-STEMI, our data support deferring a loading dose of prasugrel until a decision is made about revascularization. This strategy allows flexibility in the management of patients by providing prasugrel, with its rapid onset of action, to patients who proceed to PCI without risking bleeding complications in patients who do not proceed to PCI,” Gilles Montalescot, MD, PhD, head of the cardiac intensive care unit at the Institut de Cardiologie, Paris, and Cardiology Today’s Intervention Editorial Board member, and colleagues concluded.
In an accompanying editorial comment, Borja Ibáñez, MD, PhD, from the Centro Nacional de Investigaciones Cardiovasculares Carlos III and the interventional cardiology unit at Hospital Clinico San Carlos, Madrid, and George Dangas, MD, PhD, from the Zena and Michael A. Wiener Cardiovascular Institute and Marie-Josee and Henry R. Kravis Center for Cardiovascular Health, Mount Sinai School of Medicine, noted that the “extrapolation of the results of the ACCOAST-PCI study to all P2Y12 inhibitors in the context of non-STEMI requires caution.”
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Disclosure: The trial was sponsored by Daiichi Sankyo and Eli Lilly. Several researchers report ties with Daiichi Sankyo and Eli Lilly, as well as other pharmaceutical and device companies. Dangas is a principal investigator of a study at Mount Sinai Medical Center supported by a grant from Daiichi Sankyo and Eli Lilly; has received honoraria from AstraZeneca for participation on an advisory board; and his spouse has received honoraria for participation on an advisory board and speaker fees from AstraZeneca, Bristol-Myers Squibb and Sanofi. Ibáñez reports no relevant financial disclosures.