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Thromb Haemost 2008; 99(01): 215-222
DOI: 10.1160/TH07-09-0555
New Technologies, Diagnostic Tools and Drugs
Schattauer GmbH

A comparison of the antiplatelet effects of prasugrel and high-dose clopidogrel as assessed by VASP-phosphorylation and light transmission aggregometry

Joseph A Jakubowski
1   Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, USA
,
Christopher D Payne
2   Lilly Research Laboratories, Eli Lilly and Company, Windlesham, Surrey, UK
,
Ying G Li
1   Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, USA
,
Nagy A Farid
1   Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, USA
,
John T Brandt
1   Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, USA
,
David S Small
1   Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, USA
,
Daniel E Salazar
3   Daiichi Sankyo, Inc., Parsippany, NJ, USA
,
Kenneth J Winters
1   Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, USA
› Author AffiliationsFinancial support: This work was sponsored by Daiichi Sankyo Company, Ltd. and Eli Lilly and Company. *Parts of this work were presented as an oral presentation at the Cardiovascular Revascularization Therapy Meeting, March 3–7, 2007, Washington, D.C., USA.
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Publication History

Received: 10 September 2007

Accepted after major revision: 16 November 2007

Publication Date:
24 November 2017 (online)

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Summary

Platelet inhibition as measured by vasodilator-stimulated phosphoprotein (VASP) and light transmission aggregometry (LTA) have shown concordance following dosing of clopidogrel. No reports have directly compared theVASP assay and LTA at the levels of P2Y12 blockade after loading doses (LDs) of prasugrel or high dose clopidogrel (600 and 900 mg).The aim was to compare theVASP assay and LTA during the loading dose phase of a comparative study of prasugrel and clopidogrel. Prasugrel 60 mg LD/10 mg maintenance dose (MD) and clopidogrel 300 mg/75 mg and 600 mg/75 mg LD/MD regimens were compared in a 3-way crossover study in 41 healthy, aspirin-free subjects. Each LD was followed by seven daily MDs and a 14-day washout period. P2Y12 receptor blockade was estimated using theVASP assay, expressed as platelet reactivity index (VASP-PRI). Platelet aggregation was assessed by light transmission aggregometry (20 and 5 μM ADP).Twenty-four hoursafter prasgurel 60 mg or clopidogrel 300 mg and 600 mg, respectively, VASP-PRI decreased from ∼80% to 8.9%, 54.7%, and 39.0 %, and maximal platelet aggregation (MPA) decreased from ∼79% to 10.8%, 42.7%, and 31.2%, with an overall VASP:MPA correlation of 0.88 (p<0.01). VASP assay responses after the clopidogrel LDs showed a wider range of values (300 mg: 0–93%; 600 mg: 0–80%) than prasugrel (0–13%); MPA responses followed a similar trend. Pearson’s correlation suggested a strong agreement between VASP and LTA (20 μM ADP) for MPA (r=0.86, p<0.0001).VASP and LTA demonstrated concordance across the response range of P2Y12 receptor blockade following thienopyridine LDs.

Keywords

Clopidogrel - prasugrel - P2Y12 - thienopyridine - VASP
 

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