Li Changqing, Jia Weihua, Li Jian, Li Fangfei, Ma Jing, Zhou Lichun
Department of Neurology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
Department of Neurology, Shijingshan Teaching Hospital of Capital Medical University, Beijing Shijingshan Hospital, Beijing, China.
BMC Neurol. 2021 Mar 9;21(1):104. doi: 10.1186/s12883-021-02127-6.
Clopidogrel is an antiplatelet drug used in the treatment of ischemic stroke. Safety and efficacy of clopidogrel has been confirmed in CAPRIE, PRoFESS trials. However, these studies focused on patients aged less than 75 years. CYP2C19 polymorphisms resulted in individual differences in clopidogrel response. Our objective was to determine whether elderly stroke patients aged over 75 years would benefit from CYP2C19-genotype-guided strategy for the secondary prevention of stroke.
A retrospective analysis of patients aged 75 years or older with non-cardiogenic stroke who received 75 mg clopidogrel was performed. CYP2C19 genotype-guided group included noncarriers of CYP2C192 or CYP2C193 loss-of-function alleles (LoFA) and compared against the non-genotype-guided group which may carriers CYP2C19 LoFA or not. The primary endpoints were composite of stroke and myocardial infarction at 24 months' follow-up.
Two hundred one patients were included: 99 in the genotype-guided group and 102 in the non-genotype-guided group. Kaplan-Meier(KM)analysis showed that CYP2C19 gene polymorphism was associated with the rate of the primary endpoints (P = 0.0031). The primary endpoints occurred in 13 patients (13.1%) in the genotype-guided group and in 30 patients (29.4%) in the non-genotype-guided group (hazard ratio(HR), 0.39; 95% confidence interval(CI), 0.20 to 0.75; p = 0.004). Cox regression analysis showed that CYP2C19 genotype-guided strategy was a protective factor for the primary endpoints (HR, 0.39; 95% CI:0.20 to 0.74, P = 0.004).
The CYP2C19 genotype-guided strategy could reduce the occurrence of composite of stroke and myocardial infarction compared to a non-genotype-guided strategy for non-cardiogenic stroke patients aged 75 years or older who received clopidogrel.
氯吡格雷是一种用于治疗缺血性卒中的抗血小板药物。氯吡格雷的安全性和有效性已在CAPRIE、PRoFESS试验中得到证实。然而，这些研究主要关注年龄小于75岁的患者。CYP2C19基因多态性导致氯吡格雷反应存在个体差异。我们的目的是确定75岁以上的老年卒中患者是否能从CYP2C19基因分型指导的卒中二级预防策略中获益。
对年龄在75岁及以上、接受75mg氯吡格雷治疗的非心源性卒中患者进行回顾性分析。CYP2C19基因分型指导组包括CYP2C192或CYP2C193功能缺失等位基因（LoFA）的非携带者，并与可能携带或不携带CYP2C19 LoFA的非基因分型指导组进行比较。主要终点是随访24个月时卒中与心肌梗死的复合终点。
共纳入201例患者：基因分型指导组99例，非基因分型指导组102例。Kaplan-Meier（KM）分析显示，CYP2C19基因多态性与主要终点发生率相关（P = 0.0031）。基因分型指导组有13例患者（13.1%）发生主要终点，非基因分型指导组有30例患者（29.4%）发生主要终点（风险比[HR]，0.39；95%置信区间[CI]，0.20至0.75；P = 0.004）。Cox回归分析显示，CYP2C19基因分型指导策略是主要终点的保护因素（HR，0.39；95%CI：0.20至0.74，P = 0.004）。
对于接受氯吡格雷治疗的75岁及以上非心源性卒中患者，与非基因分型指导策略相比，CYP2C19基因分型指导策略可降低卒中和心肌梗死复合终点的发生率。
