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

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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.

Details

Authors
Organisations
External organisations
  • Eli Lilly and Company
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Microbiology in the medical area

Keywords

  • Activated GPIIb–IIIa, Platelets, Prasugrel, Surface P-selectin
Original languageEnglish
Pages (from-to)369-375
Number of pages7
JournalJournal of Thrombosis and Thrombolysis
Volume42
Issue number3
Publication statusPublished - 2016 Oct
Publication categoryResearch
Peer-reviewedYes