title: 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.
abstract: OBJECTIVE
  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.
authors.affiliation: Institut de Cardiologie, Pitié-Salpétrière University Hospital, Paris, France.
authors.forename: Miles
authors.initials: M
authors.lastname: Dalby
authors.forename: Gilles
authors.initials: G
authors.lastname: Montalescot
authors.forename: Claire
authors.initials: C
authors.lastname: Bal dit Sollier
authors.forename: Eric
authors.initials: E
authors.lastname: Vicaut
authors.forename: Thierry
authors.initials: T
authors.lastname: Soulat
authors.forename: Jean Philippe
authors.initials: JP
authors.lastname: Collet
authors.forename: Rémi
authors.initials: R
authors.lastname: Choussat
authors.forename: Vanessa
authors.initials: V
authors.lastname: Gallois
authors.forename: Gérard
authors.initials: G
authors.lastname: Drobinski
authors.forename: Ludovic
authors.initials: L
authors.lastname: Drouet
authors.forename: Daniel
authors.initials: D
authors.lastname: Thomas
mesh_terms: D000368:Aged; D001241:Aspirin / Q000627:therapeutic use*; D000077144:Clopidogrel; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D017984:Enoxaparin / Q000627:therapeutic use; D000077542:Eptifibatide; D005260:Female; D005340:Fibrinogen / Q000187:drug effects / Q000502:physiology; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy*; D010455:Peptides / Q000627:therapeutic use*; D015539:Platelet Activation / Q000187:drug effects / Q000502:physiology; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D017984:Enoxaparin; D005343:Fibrinolytic Agents; D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D005340:Fibrinogen; D000077144:Clopidogrel; D000077542:Eptifibatide; D013988:Ticlopidine; D001241:Aspirin