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

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

doi:10.1160/TH08-05-0313

Thrombosis and Haemostasis, Inhaltsverzeichnis

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

Authors

Oscar Ö. Braun^*

¹Department of Cardiology, Lund University, Sweden
Matilda Johnell^*

²Coagulation Laboratory, Department of Medical Sciences, Clinical Chemistry, Uppsala, Sweden
Christoph arenhorst

³Uppsala Clinical Research Centre and Department of Medical Sciences, Uppsala University, Sweden
Stefan James

³Uppsala Clinical Research Centre and Department of Medical Sciences, Uppsala University, Sweden
John T. Brandt

⁴Lilly Research Laboratories, Indianapolis, Indiana, USA
Joseph A. Jakubowski

⁴Lilly Research Laboratories, Indianapolis, Indiana, USA
Kenneth J. Winters

⁴Lilly Research Laboratories, Indianapolis, Indiana, USA
Lars Wallentin

³Uppsala Clinical Research Centre and Department of Medical Sciences, Uppsala University, Sweden
David Erlinge

¹Department of Cardiology, Lund University, Sweden
Agneta Siegbahn

²Coagulation Laboratory, Department of Medical Sciences, Clinical Chemistry, Uppsala, Sweden

Abstract

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

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Referenzen

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