Zhang Jinbiao, Zhang Jiangshan, Sun Hairong, Ming Tan, Liu Xinwu, Cong Yannan, Li Fang, Li Zhenguang
Int J Clin Pharmacol Ther. 2017 Oct;55(10):789-797. doi: 10.5414/CP202911.
Platelet activation and aggregation play an important role in the pathological and physiological processes of recurrent ischemic vascular events in stroke patients. The purpose of this study is to determine the association between platelet function measured in the acute period and recurrent ischemic vascular events in patients with transient ischemic attack (TIA) or minor stroke. A total of 417 patients who were within the 24-hour period of clopidogrel-aspirin therapy after onset of a minor stroke or high-risk transient ischemic attack according to the Clopidogrel in High-risk patients with Acute Nondisabling Cerebrovascular Events (CHANCE) trial were included in this study. The platelet aggregation ratio was detected using a method of continuous platelet counting; patients underwent CYP2C19 genotyping, and the baseline data were recorded. The patients underwent a 6-month follow-up period during which the recurrent ischemic vascular events were observed. Logistic regression analysis was performed to obtain the risk factors for recurrent ischemic vascular events. The number of patients with recurrent ischemic events who had an arachidonic acid-induced maximum platelet aggregation ratio (MAR-AA) (aspirin 100 mg) (31.85 ± 12.86 vs. 26.71 ± 12.44, p = 0.007) and adenosine diphosphate-induced maximum platelet aggregation ratio (MAR-ADP) after the administration of 75 mg clopidogrel for 12 ± 2 days (65.82 ± 10.72 vs. 53.10 ± 12.98, p < 0.001) was significantly higher compared with the no ischemic vascular event group. Multivariate logistic regression analyses showed that being a carrier of the CYP2C19 loss-of-function (LOF) allele (OR = 2.308, 95% CI: 1.087 ~ 4.901, p = 0.029) as well as the MAR-AA (aspirin 100 mg) (OR = 1.028, 95% CI: 1.006 ~ 1.052, p = 0.014) and MAR-ADP after the administration of 75 mg clopidogrel (OR = 1.067, 95% CI: 1.037 ~ 1.095, p < 0.001) were risk factors for ischemic vascular events. The MAR-ADP after the administration of 75 mg clopidogrel was significantly higher in patients who were carriers of the CYP2C19 (LOF) allele compared with non-carriers (57.53 ± 13.32 vs. 50.86 ± 12.55, p < 0.001), and no significant differences between the CYP2C19 LOF allele carriers and non-carriers in the MAR-ADP were detected after the administration of 300 mg clopidogrel (37.18 ± 11.36 vs. 35.86 ± 12.49, p = 0.264). Being a carrier of the CYP2C19 LOF allele has a significant influence on clopidogrel response. Platelet function is closely related to recurrent ischemic vascular events in acute minor stroke or TIA patients. .
血小板活化和聚集在中风患者复发性缺血性血管事件的病理和生理过程中起重要作用。本研究的目的是确定急性期测量的血小板功能与短暂性脑缺血发作（TIA）或轻度中风患者复发性缺血性血管事件之间的关联。根据急性非致残性脑血管事件高危患者的氯吡格雷（CHANCE）试验，共有417例在轻度中风或高危短暂性脑缺血发作发病后24小时内接受氯吡格雷-阿司匹林治疗的患者纳入本研究。采用连续血小板计数法检测血小板聚集率；患者进行CYP2C19基因分型，并记录基线数据。患者接受为期6个月的随访，在此期间观察复发性缺血性血管事件。进行逻辑回归分析以获得复发性缺血性血管事件的危险因素。与无缺血性血管事件组相比，发生复发性缺血事件的患者在服用100mg阿司匹林后花生四烯酸诱导的最大血小板聚集率（MAR-AA）（31.85±12.86 vs.26.71±12.44，p = 0.007）以及在服用75mg氯吡格雷12±2天后二磷酸腺苷诱导的最大血小板聚集率（MAR-ADP）（65.82±10.72 vs.53.10±12.98，p <0.001）显著更高。多因素逻辑回归分析显示，作为CYP2C19功能丧失（LOF）等位基因的携带者（OR = 2.308，95%CI：1.0874.901，p = 0.029）以及服用100mg阿司匹林后的MAR-AA（OR = 1.028，95%CI：1.0061.052，p = 0.014）和服用75mg氯吡格雷后的MAR-ADP（OR = 1.067，95%CI：1.037~1.095，p <0.001）是缺血性血管事件的危险因素。与非携带者相比，CYP2C19（LOF）等位基因携带者在服用75mg氯吡格雷后的MAR-ADP显著更高（57.53±13.32 vs.50.86±12.55，p <0.001），而在服用300mg氯吡格雷后，CYP2C19 LOF等位基因携带者与非携带者在MAR-ADP方面未检测到显著差异（37.18±11.36 vs.35.86±12.49，p = 0.264）。作为CYP2C19 LOF等位基因的携带者对氯吡格雷反应有显著影响。血小板功能与急性轻度中风或TIA患者复发性缺血性血管事件密切相关。
