Observation Of Clopidogrel Gene In Patients With Ischemic Stroke And Acute Coronary Syndrome

[Background] Cardiovascular and cerebrovascular diseases has been the main reason of death around the world. Clopidorel has been the most common antiplatelet drug because it can effectively reduce the risk and death of cardiovascular and cerebrovascular diseases and has less adverse effects than others. But there is wide range individual variation of Clopidogrel response between different people, and lots of patients will perform low response to Clopidogrel during antiplatelet therapy. Renctly, more and more studies have proved that the variation of Clopidogrel response is due to gene polymorphisms. To illustrate this phenomenon, we carried out a prospective and observational multi-center study based on ischemic stroke and acute coronary syndrome patients in China.[Methods] Our study was based on ischemic stroke and acute coronary syndrome patients. First, we performed genotyping of10candidate SNPs regarding with Clopidogrel. Then we carried on VerifyNow tests to measure platelet activity on the6±1d after Clopidogrel loading dose300mg of stroke patients and on the30+7d of ACS patients. And we did the follow-up visit at1mon,3mon and12mon after Clopidogrel loading dose to observe the clinical end points(cardiovascular death, nonfatal myocardial infarction or ischemic stroke) and safety.[Results] Our stydy demonstrated that the significant association between CYP2C19loss-of-function allele CYP2C19*2and high on-treatment platelet reactivity and the clinical ischemic events during ischemic stroke patients at the first time, and has confirmed that CYP2C19*2is an independent risk factor of Clopidogrel resistence. In the preliminary study, irrespective of the carriage of the CYP2C19*2or*3allele, a high prevalence of the CYP2C19LOF genotype (60.4%) was observed. And in our study, the VerifyNow test also showed25.9%patients with Clopidogrel resistence. It means that a large amounts of patients did not get their platelet function under control when receiving antiplatelet therapy with Clopidogrel.[Conclusion] The pharmacogenomics study between Chinese ischemic stroke and acute coronary syndrome patients demonstrated that CYP2C19*2has a significant association with Clopidogrel resistence and clinical ischemic events and can serve as a theoretical basis when impleting the antiplatelet individualized treatment.