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Oscar Braun

Physician

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

Author

  • Oscar Braun
  • Matilda Johnell
  • Christoph Varenhorst
  • Stefan James
  • John T. Brandt
  • Joseph A. Jakubowski
  • Kenneth J. Winters
  • Lars Wallentin
  • David Erlinge
  • Agneta Siegbahn

Summary, in English

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.

Department/s

  • Cardiology

Publishing year

2008

Language

English

Pages

626-633

Publication/Series

Thrombosis and Haemostasis

Volume

100

Issue

4

Document type

Journal article

Publisher

Schattauer GmbH

Topic

  • Cardiac and Cardiovascular Systems

Keywords

  • flow cytometry
  • tissue factor
  • platelet markers
  • CAD
  • thienopyridines

Status

Published

ISBN/ISSN/Other

  • ISSN: 0340-6245