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Thromb Haemost 2008; 100(04): 626-633
DOI: 10.1160/TH08-05-0313
Platelets and Blood Cells
Schattauer GmbH

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

Oscar Ö. Braun   *
1   Department of Cardiology, Lund University, Sweden
,
Matilda Johnell   *
2   Coagulation Laboratory, Department of Medical Sciences, Clinical Chemistry, Uppsala, Sweden
,
Christoph arenhorst
3   Uppsala Clinical Research Centre and Department of Medical Sciences, Uppsala University, Sweden
,
Stefan James
3   Uppsala Clinical Research Centre and Department of Medical Sciences, Uppsala University, Sweden
,
John T. Brandt
4   Lilly Research Laboratories, Indianapolis, Indiana, USA
,
Joseph A. Jakubowski
4   Lilly Research Laboratories, Indianapolis, Indiana, USA
,
Kenneth J. Winters
4   Lilly Research Laboratories, Indianapolis, Indiana, USA
,
Lars Wallentin
3   Uppsala Clinical Research Centre and Department of Medical Sciences, Uppsala University, Sweden
,
David Erlinge
1   Department of Cardiology, Lund University, Sweden
,
Agneta Siegbahn
2   Coagulation Laboratory, Department of Medical Sciences, Clinical Chemistry, Uppsala, Sweden
› Author Affiliations Financial support: This study was funded by Daiichi Sankyo Co, Ltd., Tokyo, Japan and Eli Lilly and Company, Indianapolis, IN, USA.
Further Information

Publication History

Received 19 May 2008

Accepted after minor revision 23 July 2008

Publication Date:
22 November 2017 (online)

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Summary

Prasugrel, a novel P2Y12 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 aspirintreated 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 µM 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 MFI, 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 procoagulant and pro-inflammatory markers with prasugrel suggest the potential to reduce cardiovascular events both in the acute setting and in longterm treatment.

Keywords

CAD - thienopyridines - platelet markers - tissue factor - flow cyto metry

* These authors contributed equally to this work.


 

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