title: Effect of eptifibatide for acute coronary syndromes: rapid versus late administration--therapeutic yield on platelets (The EARLY Platelet Substudy).
abstract: BACKGROUND
  Receptors other than GP IIb/IIIa may mediate leukocyte-platelet-endothelial interactions that obstruct the microvasculature in acute coronary syndromes (ACS) and cause microinfarcts. The effect of eptifibatide on these receptors was investigated in a substudy of the EARLY Trial.
  
  
  METHODS
  Patients received early (in the Emergency Department, n = 27) or late (12-24 h, n = 28) eptifibatide. Ten platelet receptors by flow cytometry and platelet aggregation (10 micromol/L ADP) were measured serially at baseline, and at 3, 6, 12 and 24 h after randomization.
  
  
  RESULTS
  Platelet aggregation was rapidly inhibited by early eptifibatide therapy (baseline, 72 +/- 20%; 3 h post, 7 +/- 9%; p < 0.001). No significant differences were seen in either group for CD 31, CD 63, CD 107a, CD 107b, CD 41 (GPIIb/IIIa expression), or CD 62p. Leukocyte-platelet aggregate formation (mean fluorescense intensity) trended upward after presentation (early baseline, 43.1 +/- 26.0 versus 65.8 +/- 35.6, p =.09). PAC-1 (GP IIb/IIIa activity), CD 51/61 (vitronectin receptor) and CD 42b (GP Ib) were inhibited by eptifibatide (p <.05).
  
  
  CONCLUSIONS
  In Emergency Department patients with unstable angina, early eptifibatide rapidly and profoundly inhibits platelet aggregation and reduces GP IIb/IIIa activity and the expression of CD51/61 and CD 42b; the latter two effects may also contribute to the drug's anti-thrombotic effect. However, platelet-leukocyte aggregate formation, a marker of platelet activity rises within 24 h after presentation despite eptifibatide therapy and is a potential mechanism for microvascular obstruction.
authors.affiliation: Sinai Center for Thrombosis Research, Baltimore, Maryland 21215, USA. pgurbel@lifebridgehealth.org
authors.forename: Paul A
authors.initials: PA
authors.lastname: Gurbel
authors.forename: Brian
authors.initials: B
authors.lastname: Galbut
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Bliden
authors.forename: Raymond D
authors.initials: RD
authors.lastname: Bahr
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Roe
authors.forename: Victor L
authors.initials: VL
authors.lastname: Serebruany
authors.forename: W Brian
authors.initials: WB
authors.lastname: Gibler
authors.forename: Robert H
authors.initials: RH
authors.lastname: Christenson
authors.forename: E Magnus
authors.initials: EM
authors.lastname: Ohman
mesh_terms: D000208:Acute Disease; D000368:Aged; D000369:Aged, 80 and over; D000789:Angina, Unstable / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects; D002469:Cell Separation; D003327:Coronary Disease / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000077542:Eptifibatide; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000008:administration & dosage*; D010974:Platelet Aggregation / Q000187:drug effects* / Q000502:physiology; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic / Q000379:methods; D018709:Statistics, Nonparametric
chemical_list: D010455:Peptides; D010980:Platelet Membrane Glycoproteins; D000077542:Eptifibatide