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

Claire Bal dit Sollier; Natacha Berge; Bernadette Boval; Lionel Hovsepian

doi:10.1160/TH08-07-0481

Thrombosis and Haemostasis, Inhaltsverzeichnis

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

¹IVS, Hôpital Lariboisière, Paris, France

,

Natacha Berge

¹IVS, Hôpital Lariboisière, Paris, France

,

Bernadette Boval

²Haematology Laboratory, Hôpital Lariboisière, Paris, France

,

Lionel Hovsepian

³SGS-ASTER, Paris, France

› Institutsangaben

Abstract

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

Volltext

Referenzen

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