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Thromb Haemost 2009; 101(01): 116-122
DOI: 10.1160/TH08-07-0481
Platelets and Blood Cells
Schattauer GmbH

Functional variability of platelet response to clopidogrel correlates with P2Y12 receptor occupancy

Claire Bal dit Sollier
1   IVS, Hôpital Lariboisière, Paris, France
,
Natacha Berge
1   IVS, Hôpital Lariboisière, Paris, France
,
Bernadette Boval
2   Haematology Laboratory, Hôpital Lariboisière, Paris, France
,
Lionel Hovsepian
3   SGS-ASTER, Paris, France
› Author AffiliationsFinancial support: This study was supported by a research grant from sanofi-aventis and Bristol-Myers Squibb.
Further Information

Publication History

Received: 25 July 2008

Accepted after minor revision: 15 October 2008

Publication Date:
23 November 2017 (online)

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Summary

Summary Interindividual variability of response to clopidogrel is currently a subject of much interest. We tested the hypothesis that functional variability in the platelet response to clopidogrel correlates with occupancy of the platelet P2Y12 receptor by clopidogrel active metabolite. Healthy subjects were screened after seven days’ treatment with clopidogrel 75 mg/day to select three clopidogrel-response groups (n=12/group), defined as ‘average’ (40–60% inhibition of platelet aggregation [IPA]), ‘low’ (<10% IPA) or ‘high’ (>80% IPA) responders. After a two- to six-week wash-out period, subjects were randomized (double-blind) to clopidogrel 75 mg/day (n=10/group) for 10 days, followed by clopidogrel 300 mg on day 11, or placebo (n=2/group). IPA induced by adenosine diphosphate (ADP), and P2Y12 receptor occupancy were measured repeatedly. The incidence of low responders was 3.7%, and low responses to clopidogrel were maintained during the randomized evaluation phase. Treatment with clopidogrel for 10 days induced a significant increase in P2Y12 receptor occupancy in each group of responders versus placebo; receptor affinity was unchanged. This reduction correlated with IPA response (r=0.54). The additional 300 mg dose of clopidogrel on top of 75 mg chronic treatment increased IPA and P2Y12 receptor occupancy in all groups, but relatively more in low responders. Variability in the response to clopidogrel appears to be linked to differences in P2Y12 receptor occupancy. An additional 300 mg dose of clopidogrel improves both IPA and P2Y12 receptor occupancy mostly in the subset of ‘low’ responders.

Keywords

Clopidogrel - platelet - variability of response
 

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