[The inter-individual variability of the response to clopidogrel].
Clopidogrel is an anti-platelet aggregation drug with proven efficacy in the prevention of atherothrombotic complications. However, according to studies, between 5 and 20% of patients have further thrombotic episodes despite treatment with clopidogrel. The principal ex vivo evaluation methods of clopidogrel's efficacy are platelet aggregometry, and using flow cytometry to measure platelet activation and the quantatitive analysis of VASP phosphorylation. VASP analysis is the most selective method for clopidogrel's effect. These tests show great inter-individual variability in the response to treatment. This variability is such that about a third of treated patients show an "insufficient" response to clopidogrel. The exact causes of this variability have not yet been clearly identified. They could correspond with observer error, inter-individual variability in intestinal absorption or hepatic metabolism, or polymorphism of clopidogrel's target, the P2Y12 receptor. Accordingly it may be necessary to adapt the dose of clopidogrel or to use an alternative treatment. Failure to respond to clopidogrel would be a risk factor for atherothrombotic complications, but this association has yet to be demonstrated.
Gachet
C
C
INSERM U311, Etablissement Français du Sang-Alsace, Spielmann, Strasbourg. christian.gachet@efs-alsace.fr
Aleil
B
B
D015815:Cell Adhesion Molecules / Q000097:blood; D000077144:Clopidogrel; D005434:Flow Cytometry; D006801:Humans; D007408:Intestinal Absorption; D008099:Liver / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics; D008840:Microfilament Proteins; D015394:Molecular Structure; D010750:Phosphoproteins / Q000097:blood; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D011110:Polymorphism, Genetic; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2 / Q000235:genetics / Q000502:physiology; D058925:Receptors, Purinergic P2Y12; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D000098662:Vasodilator-Stimulated Phosphoprotein
D015815:Cell Adhesion Molecules; D008565:Membrane Proteins; D008840:Microfilament Proteins; C548576:P2RY12 protein, human; D010750:Phosphoproteins; D010975:Platelet Aggregation Inhibitors; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; D058925:Receptors, Purinergic P2Y12; D000098662:Vasodilator-Stimulated Phosphoprotein; D000077144:Clopidogrel; D013988:Ticlopidine