Mechanisms fo Clopidogrel Resistance in Older Adults

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A clopidogrel resistance rate of 40-50% has been found in the population over 70 years of age, whereas biological resistance, associated with an increased risk of cardiovascular events, is observed in about 20-30% of younger patients. One hypothesis is that the active metabolite is less available in resistant patients. Indeed, 85% of the absorbed clopidogrel undergoes inactivation by esterases. Then the remaining fraction undergoes two steps of metabolisation to the active thiol metabolite by CYP450, essentially the isoform 2C19. In older adults, increased esterase activity and/or decreased CYP450 2C19 activity may lead to a decreased concentration of the active metabolite. Multiple chronic conditions and polypharmacy encountered in older individuals are associated with basal platelet hyperactivity, and may also contribute to a poor response to clopidogrel. No data on the relationship between platelet response and circulating metabolite levels, or on the determinants of response to clopidogrel, are currently available in the geriatric population. Therefore, we propose to analyse the relationship between age and platelet and extra-platelet mechanisms potentially involved in the variability of response to clopidogrel.

2021-07-12

2025-07-12

2026-01-12

Recruiting

100

Inclusion Criteria: Consecutive patients per 10-year age range, (20 patients per age range from 50 to 100 years included) : * in consultation or hospitalization in one of the participating centres, * treatment with clopidogrel 75 mg/d for at least 10 days for primary or secondary prevention of cardiovascular events. * who have received the information and have not expressed their opposition to participate in the study and who have given their written consent for the performance of genetic examinations and the realization of a biocollection * affiliated to French social security system Exclusion criteria : * treatment with another antithrombotic agent, * myeloproliferative syndrome, * platelet count \< 100 G/L, * acute inflammatory situation: severe sepsis, documented acute infection, chronic systemic inflammatory disease or active cancer, * under dialysis, * no participation in another clinical study, * deprived of liberty

{'studyType': 'OBSERVATIONAL', 'patientRegistry': False, 'designInfo': {'observationalModel': 'COHORT', 'timePerspective': 'PROSPECTIVE'}, 'bioSpec': {'retention': 'SAMPLES_WITH_DNA', 'description': 'Centralized determination of clopidogrel and active metabolite (pharmacology Samples) Centralized determination of plasma markers of platelet activation (hematology Samples) Centralized study of genetic polymorphisms (pharmacology Samples)'}, 'enrollmentInfo': {'count': 100, 'type': 'ESTIMATED'}}

2023-11-27