title: Prasugrel 5 mg inhibits platelet P-selectin and GPIIb-IIIa expression in very elderly and non elderly: results from the GENERATIONS trial, a pharmacodynamic study in stable CAD patients.
abstract: Platelet P-selectin and activated glycoprotein IIb-IIIa (GPIIb-IIIa) are markers of platelet activation and mediates platelet aggregation. Prasugrel (Pras) 5 mg may be used in very elderly (VE) acute coronary syndrome (ACS) patients undergoing PCI, but its effect on platelet P-selectin and activated GPIIb-IIIa in those patients is not known. Stable ACS patients, VE (78 ± 5 years, n = 23) and non-elderly (NE) (55 ± 5 years, n = 22) were randomized to Pras (5 or 10 mg) or clopidogrel (Clop) 75 mg during three 12-day periods. Platelet activation markers were measured by flow cytometry on unstimulated or stimulated (adenosine diphosphate (ADP) 20 μM) platelets, before and after each dosing period.
  
  
  RESULTS
  At baseline there was no difference in platelet activation markers, either unstimulated or ADP-stimulated, between NE and VE. Pras 5 mg reduced both ADP-stimulated platelet P-selectin and activated GPIIb-IIIa in VE (p < 0.01 for both analyses) and NE (p < 0.001 and p < 0.05, respectively). Clop 75 mg had a similar effect as Pras 5 mg but did not significantly reduce activated GPIIb-IIIa in VE. Prasugrel 10 mg resulted in decreased platelet activation in both age groups compared to Clop 75 mg (p < 0.01).
  
  
  CONCLUSIONS
  In VE and NE-patients, Pras 5 mg inhibited platelet P-selectin expression similar to Clop 75 mg and Pras 10 mg. Prasugrel 10 mg inhibited platelet P-selectin expression better than Clop 75 mg. Prasugrel 10 mg and 5 mg, but not Clop 75 mg, significantly inhibited activated GPIIb-IIIa in VE. This platelet reactivity data support the use of Pras 5 mg for VE patients.
authors.affiliation: Department of Cardiology, Clinical Sciences, Lund University, Lund, Sweden. henrik.wagner@med.lu.se.
authors.forename: Henrik
authors.initials: H
authors.lastname: Wagner
authors.affiliation: Department of Reumatology, Clinical Sciences, Lund University, Lund, Sweden.
authors.forename: Christian
authors.initials: C
authors.lastname: Lood
authors.affiliation: Department of Cardiology, Clinical Sciences, Lund University, Lund, Sweden.
authors.forename: Catharina
authors.initials: C
authors.lastname: Borna
authors.affiliation: Department of Cardiology, Clinical Sciences, Lund University, Lund, Sweden.
authors.forename: Olof
authors.initials: O
authors.lastname: Gidlöf
authors.affiliation: Section of Microbiology, Immunology and Glycobiology, Department of Laboratory Medicine Lund, Lund University, Lund, Sweden.
authors.forename: Lennart
authors.initials: L
authors.lastname: Truedsson
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Brown
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Chunmei
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Winters
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Jakubowski
authors.affiliation: Department of Cardiology, Clinical Sciences, Lund University, Lund, Sweden.
authors.forename: David
authors.initials: D
authors.lastname: Erlinge
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000188:drug therapy; D006801:Humans; D008875:Middle Aged; D019007:P-Selectin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015539:Platelet Activation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000068799:Prasugrel Hydrochloride / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D019007:P-Selectin; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D000077144:Clopidogrel; D000068799:Prasugrel Hydrochloride; D013988:Ticlopidine
keywords: Activated GPIIb–IIIa; Platelets; Prasugrel; Surface P-selectin