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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

Wagner, Henrik LU ; Lood, Christian LU ; Borna, Catharina LU ; Gidlöf, Olof LU ; Truedsson, Lennart LU ; Brown, Patricia; Zhou, Chunmei; Winters, Kenneth; Jakubowski, Joseph A. and Erlinge, David LU (2016) In Journal of Thrombosis and Thrombolysis 42(3). p.369-375
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... (More)

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.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Activated GPIIb–IIIa, Platelets, Prasugrel, Surface P-selectin
in
Journal of Thrombosis and Thrombolysis
volume
42
issue
3
pages
7 pages
publisher
Springer
external identifiers
  • Scopus:84966564902
ISSN
0929-5305
DOI
10.1007/s11239-016-1372-1
language
English
LU publication?
yes
id
be2dbfa7-94b2-4ec4-8d09-80864a906deb
date added to LUP
2016-06-02 16:29:57
date last changed
2016-10-05 13:04:14
@misc{be2dbfa7-94b2-4ec4-8d09-80864a906deb,
  abstract     = {<p>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 &lt;0.01 for both analyses) and NE (p &lt;0.001 and p &lt;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 &lt;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.</p>},
  author       = {Wagner, Henrik and Lood, Christian and Borna, Catharina and Gidlöf, Olof and Truedsson, Lennart and Brown, Patricia and Zhou, Chunmei and Winters, Kenneth and Jakubowski, Joseph A. and Erlinge, David},
  issn         = {0929-5305},
  keyword      = {Activated GPIIb–IIIa,Platelets,Prasugrel,Surface P-selectin},
  language     = {eng},
  month        = {05},
  number       = {3},
  pages        = {369--375},
  publisher    = {ARRAY(0x9651ec0)},
  series       = {Journal of Thrombosis and Thrombolysis},
  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},
  url          = {http://dx.doi.org/10.1007/s11239-016-1372-1},
  volume       = {42},
  year         = {2016},
}