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CLINICAL RESEARCH: CLINICAL TRIALS

Eptifibatide provides additional platelet inhibition in Non–ST-Elevation myocardial infarction patients already treated with aspirin and clopidogrel

Results of the platelet activity extinction in Non–Q-Wave myocardial infarction with aspirin, clopidogrel, and eptifibatide (PEACE) study

Miles Dalby, MD^*, Gilles Montalescot, MD, PhD^*,*, Claire Bal dit Sollier, MD, Eric Vicaut, MD, PhD, Thierry Soulat, MD, Jean-Philippe Collet, MD, PhD^*, Rémi Choussat, MD^*, Vanessa Gallois, MSc^*, Gérard Drobinski, MD, PhD^*, Ludovic Drouet, MD and Daniel Thomas, MD^*

^* Institut de Cardiologie, Pitié-Salpétrière University Hospital, Paris, France
Department of Haematology, Hospital Lariboisiere, Paris, France
Unite de Recherche Clinique, Hospital Lariboisiere, Paris, France

Manuscript received February 5, 2003; revised manuscript received August 13, 2003, accepted August 25, 2003.

^* Reprint requests and correspondence: Dr. Gilles Montalescot, Institut de Cardiologie, Bureau 2-236, Pitié-Salpétrière University Hospital, 47 Boulevard de l'Hôpital, 75013 Paris, France.
gilles.montalescot{at}psl.ap-hop-paris.fr

This work will be presented in part at the Scientific Sessions of the American College of Cardiology, Chicago, Illinois, March 2003.

OBJECTIVES: The present study hypothesis was that eptifibatide offered further antiplatelet efficacy above clopidogrel in non–ST-elevation myocardial infarction (NSTEMI) patients before an expeditive coronary intervention.

BACKGROUND: Although thienopyridines and glycoprotein (GP) IIb/IIIa antagonists are often co-prescribed in the context of NSTEMI, the antiplatelet interaction of these agents is poorly described and the superiority of GP IIb/IIIa antagonists above thienopyridine treatment alone is not clear.

METHODS: Thirty-two NSTEMI patients treated with aspirin and enoxaparin were studied using flow cytometry to define parameters of platelet activation with a panel of agonists before clopidogrel, after clopidogrel, and during an eptifibatide infusion following the clopidogrel load.

RESULTS: After platelet activation with adenosine diphosphate, thrombin receptor-activating peptide, or U46-619, relative reductions in conformationally activated GP IIb/IIIa receptor expression (evaluated with PAC-1) of 48%, 43%, and 33%, respectively (all p < 0.0001), were seen with clopidogrel, but further 80%, 78%, and 72% (all p < 0.0001) reductions were seen with eptifibatide. With the same agonists, fibrinogen binding was significantly reduced after clopidogrel by 70%, 64%, and 81% (all p < 0.0001) and again further reduced with eptifibatide by 90%, 95%, and 69% (all p < 0.0001). The total number of GP IIb/IIIa receptors (measured as P2 expression) and P-selectin expression fell after clopidogrel, after ex vivo stimulation with the same agonists; however, both parameters increased slightly during the eptifibatide infusion.

CONCLUSIONS: The activated GP IIb/IIIa expression and fibrinogen binding findings indicate that eptifibatide provides significant potent antiplatelet activity above aspirin and clopidogrel, suggesting additive immediate protection in the treatment of NSTEMI. The P2 and P-selectin findings suggest the possibility of a partial agonist and/or pro-inflammatory effect.

Abbreviations and Acronyms   ADP = adenosine diphosphate   Fg = fibrinogen   GP = glycoprotein   IV = intravenous   Mab = monoclonal antibody   NSTEMI = non–ST-elevation myocardial infarction   PCI = percutaneous coronary intervention   PEACE = Platelet activity Extinction in non–Q-wave myocardial infarction with Aspirin Clopidogrel and Eptifibatide study   RI = relative increase   RR = relative reduction   TRAP = thrombin receptor-activating peptide

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