Evaluation of the Biological Response to Clopidogrel in Patients With Ischemic Stroke

• Status: Completed
• Trial end date: 2015-12-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Centre Hospitalier Universitaire de Saint Etienne
• Collaborator: Groupe de Recherche sur la Thrombose
• Treatments: Clopidogrel; Ticlopidine

Criteria

Inclusion Criteria:

• Consent signed

• Patients with non-cardioembolic AIC requiring initiation of treatment with clopidogrel as usual indications

• normal standard biological tests

Exclusion Criteria:

• Need to continue aspirin therapy

• Patients with a recurrence of clopidogrel AIC

• Patient already tacking clopidogrel

• Drugs interfering with the adrenergic system alpha blockers, alpha 2 receptor agonists (alpha-methyldopa) and alpha2 receptor inhibitors (Mianserin, Mirtazapine, yohimbine)

• Contra indication of clopidogrel and / or any of its excipients