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Greater reduction of platelet activation markers and platelet-monocyte aggregates by prasugrel compared to clopidogrel in stable coronary artery disease

Braun, Oscar LU ; Johnell, Matilda; Varenhorst, Christoph; James, Stefan; Brandt, John T.; Jakubowski, Joseph A.; Winters, Kenneth J.; Wallentin, Lars; Erlinge, David LU and Siegbahn, Agneta (2008) In Thrombosis and Haemostasis 100(4). p.626-633
Abstract
Prasugrel, a novel P2Y(12) ADP-receptor antagonist, has been reported to achieve greater inhibition of platelet aggregation compared to clopidogrel as assessed by light transmission aggregometry. It was the objective of this study to investigate the effect of prasugrel on alternative markers of platelet activation in comparison to a high loading dose and the approved maintenance dose of clopidogrel. One hundred ten aspirin-treated patients with stable coronary artery disease were randomized to a loading dose (LD, day 1)/ maintenance dose (MD, days 2-29) of prasugrel 60 mg/10 mg or clopidogrel 600 mg/75 mg. Platelet activation markers were analyzed by whole blood flow cytometry pre-dose and at 2 and 24 hours after LD and pre-dose at 14 and... (More)
Prasugrel, a novel P2Y(12) ADP-receptor antagonist, has been reported to achieve greater inhibition of platelet aggregation compared to clopidogrel as assessed by light transmission aggregometry. It was the objective of this study to investigate the effect of prasugrel on alternative markers of platelet activation in comparison to a high loading dose and the approved maintenance dose of clopidogrel. One hundred ten aspirin-treated patients with stable coronary artery disease were randomized to a loading dose (LD, day 1)/ maintenance dose (MD, days 2-29) of prasugrel 60 mg/10 mg or clopidogrel 600 mg/75 mg. Platelet activation markers were analyzed by whole blood flow cytometry pre-dose and at 2 and 24 hours after LD and pre-dose at 14 and 29 days. After stimulation with 20 mu M ADP, 2 hours after LD, significantly lower expression of activated GPIIb/IIIa (4.3 vs. 21.8 [mean fluorescent intensity (MFI)], p < 0.001) and P-selectin (2.0 vs. 11.7 MR, p < 0.001) along with decreased formation of platelet-monocyte aggregates (16.4% vs. 29.6% positive cells, p < 0.001) was observed with prasugrel versus clopidogrel. All these effects were maintained through 24 hours and during the MD period. In conclusion, prasugrel 60 mg LD and 10 mg MD inhibit several markers of platelet activation and the formation of platelet-monocyte aggregates more effectively than a 600 mg LD and 75 mg MD of clopidogrel. Attenuated platelet aggregation and reduced expression of platelet pro-coagulant and pro-inflammatory markers with prasugrel suggest the potential to reduce cardiovascular events both in the acute setting and in long-term treatment. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
flow cytometry, tissue factor, platelet markers, CAD, thienopyridines
in
Thrombosis and Haemostasis
volume
100
issue
4
pages
626 - 633
publisher
F K Schattauer Verlag Gmbh
external identifiers
  • wos:000260216000018
  • scopus:54949112440
ISSN
0340-6245
DOI
10.1160/TH08-05-0313
language
English
LU publication?
yes
id
ebe8137c-3a9a-4219-9e15-7b5f2a127b90 (old id 1284847)
date added to LUP
2009-02-09 09:03:00
date last changed
2017-10-01 04:21:53
@article{ebe8137c-3a9a-4219-9e15-7b5f2a127b90,
  abstract     = {Prasugrel, a novel P2Y(12) ADP-receptor antagonist, has been reported to achieve greater inhibition of platelet aggregation compared to clopidogrel as assessed by light transmission aggregometry. It was the objective of this study to investigate the effect of prasugrel on alternative markers of platelet activation in comparison to a high loading dose and the approved maintenance dose of clopidogrel. One hundred ten aspirin-treated patients with stable coronary artery disease were randomized to a loading dose (LD, day 1)/ maintenance dose (MD, days 2-29) of prasugrel 60 mg/10 mg or clopidogrel 600 mg/75 mg. Platelet activation markers were analyzed by whole blood flow cytometry pre-dose and at 2 and 24 hours after LD and pre-dose at 14 and 29 days. After stimulation with 20 mu M ADP, 2 hours after LD, significantly lower expression of activated GPIIb/IIIa (4.3 vs. 21.8 [mean fluorescent intensity (MFI)], p &lt; 0.001) and P-selectin (2.0 vs. 11.7 MR, p &lt; 0.001) along with decreased formation of platelet-monocyte aggregates (16.4% vs. 29.6% positive cells, p &lt; 0.001) was observed with prasugrel versus clopidogrel. All these effects were maintained through 24 hours and during the MD period. In conclusion, prasugrel 60 mg LD and 10 mg MD inhibit several markers of platelet activation and the formation of platelet-monocyte aggregates more effectively than a 600 mg LD and 75 mg MD of clopidogrel. Attenuated platelet aggregation and reduced expression of platelet pro-coagulant and pro-inflammatory markers with prasugrel suggest the potential to reduce cardiovascular events both in the acute setting and in long-term treatment.},
  author       = {Braun, Oscar and Johnell, Matilda and Varenhorst, Christoph and James, Stefan and Brandt, John T. and Jakubowski, Joseph A. and Winters, Kenneth J. and Wallentin, Lars and Erlinge, David and Siegbahn, Agneta},
  issn         = {0340-6245},
  keyword      = {flow cytometry,tissue factor,platelet markers,CAD,thienopyridines},
  language     = {eng},
  number       = {4},
  pages        = {626--633},
  publisher    = {F K Schattauer Verlag Gmbh},
  series       = {Thrombosis and Haemostasis},
  title        = {Greater reduction of platelet activation markers and platelet-monocyte aggregates by prasugrel compared to clopidogrel in stable coronary artery disease},
  url          = {http://dx.doi.org/10.1160/TH08-05-0313},
  volume       = {100},
  year         = {2008},
}