Association of clopidogrel high on-treatment reactivity with clinical outcomes and gene polymorphism in acute ischemic stroke patients

作者：Hefei Fu, Pan Hu, Chunmei Ma, Fei Peng, Zhiyi He · 发表于：Medicine · 年份：2020 · DOI：10.1097/md.0000000000019472 · 被引用次数：24 · 研究领域：Antiplatelet Therapy and Cardiovascular Diseases、Acute Ischemic Stroke Management、Venous Thromboembolism Diagnosis and Management

High on-treatment platelet reactivity (HTPR) was suggested to be better correlated with recurrent ischemic events as compared with gene polymorphism, whereas most of the results were from white populations with acute coronary disease. The evidence is relatively limited regarding HTPR and its genetic determinants in predicting clinical outcomes of stroke among Chinese-Han patients.A prospective study including 131 Chinese-Han stroke patients treated with clopidogrel was analyzed. Platelet function was assessed by light transmission aggregometry (LTA)- adenosine diphosphate (ADP) method. HTPR was defined as 5 μM ADP induced platelet aggregation > 46%. CYP2C19 and P2Y12 genotype were detected using the PCR-RFLP method. The difference in the occurrence of the primary endpoint was analyzed according to platelet function and genetic status.Sixty-three (48.1%) subjects displayed HTPR after administering clopidogrel for 1 week. The prevalence of HTPR was significantly higher in CYP2C19 loss-of-function (LOF) alleles (2, 3) carriers vs wild-type homozygotes (71.7% vs 32.1%, P < .01), and logistic regression analysis showed that carriers of CYP2C19 LOF alleles were an independent risk factor of HTPR. Survival analysis indicated that patients with HTPR had an increased risk of primary endpoints (20.6% vs 7.3%, P = .04), whereas the presence of CYP2C19 LOF alleles or P2Y12 H2 haplotype did not increase the incidence of ischemic events. Cox regression analysis demonstrated that HTPR was a...