News:Eptifibatide: Results of BRIEF-PCI Trial Released

November 4, 2007 By Scott P. Williams [mailto:swilliams@perfuse.org]

Currently platelet glycoprotein IIb/IIIa inhibitors, such as eptifibatide, are used to reduce the risk of ischemic events for patients who undergo percutaneous coronary intervention (PCI). In 2000 the ESPRIT trial established double boluses of 180 mcg/Kg, 10 minutes apart, followed by an 18 – 24 hour infusion at 2 mcg/Kg/min as the standard eptifibatide treatment. It has been hypothesized that current practice patterns that utilize oral dual anti-platelet therapy, including a loading dose of clopidogrel, may reduce or obviate the need for an 18 hour eptifibatide infusion. The BRIEF PCI study enrolled patients with stable angina (SA), acute coronary syndrome (ACS), or ST segment elevation myocardial infarction (STEMI)(STEMIs were stable for greater than 48 hours). Patients were excluded if visible thrombus was present. The study design required the performance of a successful PCI with stenting. Patients were treated with eptifibatide during the case. Patients were randomized in a 1:1 fashion following PCI into two groups if TIMI-3 flow was obtained following PCI, and if no dissection or major side branch loss occurred. The incidence of post-procedural ischemic injury within 24 hours was the primary endpoint. The composite triple endpoint of death, MI, target vessel revascularization (TVR) and the composite quadruple endpoint of death, MI, TVR, in-hospital major bleeding were secondary endpoints.

A total of 624 patients were randomized. Half of the patients received the standard 18 hour eptifibatide treatment, while the other half received an abbreviated 2 hour infusion. Biomarkers were measured at baseline, 6 hours, and 18 hours, and 100% of patients received a 30 day follow up. The baseline characteristics (age, sex, diabetes, SA, ACS, STEMI, clopidogrel load) and procedural characteristics (femoral access, 6 French, multi-vessel, more than 2 stents, stent length, B2 or C lesions, closure device) were similar in both groups of patients.

The magnitude of ischemic injury was similar in the two groups of patients, with a rate of 30.1% for patients receiving the abbreviated eptifibatide treatment compared to 28.3% of patients receiving standard treatment (95% CI, p< 0.012 for non-inferiority). The rate of ischemic injury was similar between the two groups of patients, when they were further broken down into subgroups of diabetes, ACS and clopidogrel pre treatment. Additionally, the rates of death, MI, and TVR were nearly identical in the two groups of patients (p=NS for all three endpoints).

While there was no difference in efficacy, there was a reduction in the rate of major bleeding with the brief infusion. 4.2 % of patients treated with the standard eptifibatide treatment developed major in-hospital bleeding, compared to only 1% of patients in the abbreviated treatment group (p=0.02). Additionally, 21.2% of patients receiving the standard treatment developed minor in-hospital bleeding, while 17.6 % of abbreviated treatment patients displayed similar levels of bleeding (p=NS).

Thus, among ACS patients with a successful PCI, a brief 2 hour infusion of eptifibatide is associated with similar rates of ischemia, and lower rates of major bleeding. While a larger trial may be required to confirm non-inferiority, an abbreviated eptifibatide infusion may be safer than the current 18 hour infusion.

References 1. AY Fung, J Saw, A Starovoytov, C Densem, P Jokhi, SJ Walsh, RS Fox, KH Humphries, E Aymong, DR Ricci, JG Webb, JN Hamburger, RG Carere, CE Buller, The BRIEF-PCI Trial. St. Paul's Hospital & Vancouver General Hospital, University of British Columbia, Vancouver, Canada.