title: Association between platelet receptor occupancy after eptifibatide (integrilin) therapy and patency, myocardial perfusion, and ST-segment resolution among patients with ST-segment-elevation myocardial infarction: an INTEGRITI (Integrilin and Tenecteplase in Acute Myocardial Infarction) substudy.
abstract: BACKGROUND
  Paradoxically, fibrinolytic agents may systemically activate platelets, which in turn secrete plasminogen activator inhibitor (PAI-1), an antagonist of the fibrinolytic process in proportion to total body platelet mass. We hypothesized that improved epicardial patency, myocardial perfusion, and ST-segment resolution would be associated with higher levels of platelet receptor occupancy (RO) by a glycoprotein IIb/IIIa antagonist in ST-elevation MI (STEMI).
  
  
  RESULTS
  Patients were drawn from the low-dose tenecteplase plus eptifibatide arm of the INTEGRITI study. Angiographic and platelet RO data were analyzed at 2 independent core laboratories. To take into account the absolute platelet count and receptors available for cross-linking, absolute platelet count was multiplied by percent of available receptors to obtain the index of the absolute number of receptors available (IANRA). Percent RO was higher among patients with a patent artery (TIMI flow grade 2/3; 78.2+/-9.2, n=63 versus 63.9+/-29.7, n=7; P=0.005), those with TIMI myocardial perfusion grade 2/3 (79.6+/-9.5, n=40 versus 73.0+/-16.2, n=30; P=0.036), and those with complete (> or =70%) ST-segment resolution at 60 minutes (81.3+/-8.3%, n=27 versus 73.1+/-17.4%, n=24; P=0.034). The absolute number of glycoprotein IIb/IIIa receptors available for cross-linking was reduced (ie, the IANRA was lower) among patients with a patent artery (P=0.0015), patients with TIMI myocardial perfusion grade 2/3 (P=0.026), and patients with > or =70% ST-segment resolution (P=0.029).
  
  
  CONCLUSIONS
  This study links restoration of epicardial flow, normal myocardial perfusion, and complete ST-segment resolution with higher levels of platelet glycoprotein IIb/IIIa receptor occupancy after therapy with eptifibatide administered with tenecteplase.
authors.affiliation: TIMI Study Group and the Department of Medicine, Brigham & Women's Hospital, Harvard Medical School, Boston, Mass, USA.
authors.forename: C Michael
authors.initials: CM
authors.lastname: Gibson
authors.forename: Lisa K
authors.initials: LK
authors.lastname: Jennings
authors.forename: Sabina A
authors.initials: SA
authors.lastname: Murphy
authors.forename: David P
authors.initials: DP
authors.lastname: Lorenz
authors.forename: Robert P
authors.initials: RP
authors.lastname: Giugliano
authors.forename: Robert A
authors.initials: RA
authors.lastname: Harrington
authors.forename: Shila
authors.initials: S
authors.lastname: Cholera
authors.forename: Rajini
authors.initials: R
authors.lastname: Krishnan
authors.forename: Robert M
authors.initials: RM
authors.lastname: Califf
authors.forename: Eugene
authors.initials: E
authors.lastname: Braunwald
mesh_terms: D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage / Q000627:therapeutic use; D001241:Aspirin / Q000008:administration & dosage / Q000627:therapeutic use; D017023:Coronary Angiography; D003326:Coronary Circulation; D004359:Drug Therapy, Combination; D004562:Electrocardiography; D000077542:Eptifibatide; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D006493:Heparin / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy*; D010314:Partial Thromboplastin Time; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000187:drug effects*; D011485:Protein Binding; D014654:Vascular Patency
chemical_list: D000925:Anticoagulants; D005343:Fibrinolytic Agents; D010455:Peptides; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D006493:Heparin; D000077542:Eptifibatide; D001241:Aspirin