Ischemic stroke (AIC) is the leading cause of non-traumatic disability in adults, the second leading cause of dementia and the third leading cause of death in France.
Clopidogrel is one of the recommended first line in the secondary prevention of AIC non cardioembolic origin. However recurrences occur in approximately 9% of patients receiving clopidogrel. Some studies in patients with coronary artery disease have made the connection between these treatment failures and non-biological response to clopidogrel. This non-biological response is found for approximately 30% to 50% of patients. Several mechanisms may explain this non-response. The most accepted mechanism is pharmacokinetic. Indeed, clopidogrel is a prodrug that requires intestinal absorption by P-glycoprotein (PGP) and a transformation by hepatic cytochrome into active metabolites. The genetic polymorphism of proteins involved in these two steps explain the low plasma concentration of active metabolites and thus the low efficacy of clopidogrel in some patients.
A new pharmacodynamic hypothesis suggests the involvement of platelet alpha 2-adrenergic receptors. The activation of these receptors potentiates signaling pathway P2Y12 receptor (channel inhibited by clopidogrel) and helps reduce platelet aggregation inhibiting response to clopidogrel.
Interest in the biological response to clopidogrel in the AIC is innovative because few data are available in this area. In addition to testing a new pharmacodynamic hypothesis, we also wish to study and compare other measures of platelet function methods in order to be able to use commonly in treatment decisions.
- Clopidogrel (Plavix®)Drug
Other Names: Plavix, Clodelib, Clovelen Intervention Desc: 75 mg milligrams per days of PLAVIX ARM 1: Kind: Experimental Label: AVC Description: Patients with non-cardioembolic AIC requiring initiation of treatment with clopidogrel as usual indications
- Observation: Case-Only
- Perspective: Prospective
- Sampling: Non-Probability Sample
Patients with non-cardioembolic AIC requiring initiation of treatment with clopidogrel as usual indications
|Type||Measure||Time Frame||Safety Issue|
|Primary||adrenergic component of the platelet response||5 days after taking clopidogrel||No|
|Secondary||VASP-CMF||After 5 days taking clopidogrel||No|
|Secondary||ELISA VASP||After 5 days taking clopidogrel||No|
|Secondary||active metabolite of clopidogrel||After 5 days taking clopidogrel||No|
|Secondary||Genotyping of MDR-1 and P450 2C19||After 5 days taking clopidogrel||No|
Biospecimen Retention:Samples With DNA - Blood DNA