WASHINGTON — The adjunctive use of eptifibatide in antithrombotic regimens that are given to patients undergoing primary percutaneous coronary interventions for acute ST-segment elevation myocardial infarction significantly increases the rate of bleeding when compared with heparin alone, according to a small randomized trial.
This increased bleeding rate—plus a lack of any added benefit with eptifibatide—raises the question of whether treatment with a glycoprotein (GP) IIb/IIIa inhibitor is necessary in patients pretreated for primary PCI with a high loading dose of clopidogrel (Plavix), Dr. Michel R. Le May said at Transcatheter Coronary Therapeutics 2008.
The trial, called ASSIST (A Safety and Efficacy Study of Integrilin-Facilitated PCI in ST Elevation Myocardial Infarction), is the first randomized trial to compare eptifibatide against a control group in the setting of a high (600-mg) loading dose of clopidogrel, said Dr. Le May, director of the Coronary Care Unit Research Group at the University of Ottawa Heart Institute.
Previously, another GP IIb/IIIa inhibitor, abciximab (ReoPro), was shown to have no benefit over unfractionated heparin when patients with a ST-elevation MI (STEMI) were pretreated with a 600-mg loading dose of clopidogrel before undergoing primary PCI.
Dr. Le May noted that “in many U.S. centers, eptifibatide is now the preferred treatment for primary angioplasty, mostly because it's cheaper. It runs about $800, and abciximab is about twice the price.”
In the open-label trial, 201 patients who took eptifibatide in addition to unfractionated heparin experienced a rate of events in the composite 30-day end point of death, reinfarction, or recurrent severe ischemia that was similar to the rate in patients who received unfractionated heparin alone (6.5% and 5.5%, respectively). At 6 months, the similarity persisted (8% and 7.1%, respectively).
Eptifibatide-treated patients experienced significantly more major and minor bleeding events combined in the first 30 days after PCI than did patients who received unfractionated heparin alone (22.4% vs. 14.6%). However, the differences between the groups in the rates of major bleeding alone or minor bleeding alone did not reach statistical significance, according to the TIMI (Thrombolysis in Myocardial Infarction) score.
All of the patients in ASSIST (mean age, about 60 years) were required to have felt symptoms less than 12 hours before admission. In the unfractionated heparin-only arm of the trial, 3% received eptifibatide and 4% received abciximab as a bail-out treatment.
ASSIST was funded by Schering-Plough Canada Inc., which has exclusive U.S. marketing rights to eptifibatide, and Medtronic of Canada. Dr. Le May said that he and his associates initiated the trial independently of industry.
'Eptifibatide is now the preferred treatment for primary angioplasty, mostly because it's cheaper.' DR. LE MAY