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.
Primary Outcome Measures:
Secondary Outcome Measures:
- VASP-CMF [ Time Frame: After 5 days taking clopidogrel ]
Platelet reactivity index (PRI) by VASP CMF (flow cytometry) method
- ELISA VASP [ Time Frame: After 5 days taking clopidogrel ]
Platelet reactivity index (PRI-ELISA) using ELISA VASP
- active metabolite of clopidogrel [ Time Frame: After 5 days taking clopidogrel ]
Rate of residual plasma active metabolite of clopidogrel (R-130964)
- Genotyping of MDR-1 and P450 2C19 [ Time Frame: After 5 days taking clopidogrel ]
Genotyping of MDR-1 and P450 2C19
Blood DNA
|
|
| Enrollment: |
91 |
| Study Start Date: |
September 2013 |
| Study Completion Date: |
December 2015 |
| Primary Completion Date: |
December 2015 (Final data collection date for primary outcome measure) |
|
AVC
Patients with non-cardioembolic AIC requiring initiation of treatment with clopidogrel as usual indications
|
Drug: Clopidogrel
75 mg milligrams per days of PLAVIX
Other Name: PLAVIX(R)
|
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.
