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

J Thromb Thrombolysis. 2016 Oct;42(3):369-75. doi: 10.1007/s11239-016-1372-1.

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.

Keywords: Activated GPIIb–IIIa; Platelets; Prasugrel; Surface P-selectin.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Acute Coronary Syndrome / drug therapy
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Clopidogrel
  • Coronary Artery Disease / drug therapy
  • Humans
  • Middle Aged
  • P-Selectin / antagonists & inhibitors*
  • P-Selectin / metabolism
  • Platelet Activation / drug effects*
  • Platelet Aggregation Inhibitors / administration & dosage
  • Platelet Aggregation Inhibitors / pharmacokinetics
  • Platelet Glycoprotein GPIIb-IIIa Complex / antagonists & inhibitors*
  • Platelet Glycoprotein GPIIb-IIIa Complex / metabolism
  • Prasugrel Hydrochloride / administration & dosage
  • Prasugrel Hydrochloride / pharmacokinetics*
  • Prasugrel Hydrochloride / therapeutic use
  • Ticlopidine / administration & dosage
  • Ticlopidine / analogs & derivatives
  • Ticlopidine / pharmacokinetics
  • Ticlopidine / therapeutic use

Substances

  • P-Selectin
  • Platelet Aggregation Inhibitors
  • Platelet Glycoprotein GPIIb-IIIa Complex
  • Clopidogrel
  • Prasugrel Hydrochloride
  • Ticlopidine