阿司匹林联合氯吡格雷可降低携带CYP2C19*2功能减退等位基因的缺血性卒中患者早期神经功能恶化的风险
Aspirin Plus Clopidogrel May Reduce the Risk of Early Neurologic Deterioration in Ischemic Stroke Patients Carrying CYP2C19*2 Re-duced-Function Alleles

目的：探讨急性缺血性卒中(Ischemic Stroke, IS)患者CYP2C19*2基因多态性与早期神经功能恶化(Early neurological deterioration, END)及抗血小板治疗预防END的相关性。方法：连续纳入570例急性IS患者随机分配到阿司匹林加氯吡格雷组(双抗组，284例)或阿司匹林组(单抗组，286例)。检测治疗前和治疗后7~10天血小板聚集率和血小板–白细胞聚集率，采用质谱法检测CYP2C19*2 (rs4244285)基因型。原发终点为入院10天内END。结果：121例(21.2%)发生END。CYP2C19*2功能降低等位基因与END高发生率相关(携带者为26.8%，非携带者为16.6%，P = 0.004)。双抗组END发生率低于单抗组(17.6%:24.8%，P = 0.032)。分层分析显示，对于CYP2C19*2功能降低等位基因携带者，双抗治疗比单抗治疗更有效降低END(18.8%:34.9%，P = 0.006)。对于非携带者，双抗治疗组和单抗治疗组之间END发生率无显著差异(16.7%:16.6%，P = 0.998)。结论：阿司匹林加氯吡格雷治疗可降低携带CYP2C19*2功能降低等位基因IS患者END发生率。
Objectives: The aim of this study was to investigate the association between CYP2C19*2 variants and early neurological deterioration (END), and the effectiveness of antiplatelet therapy for preven-tion of END according to CYP2C19*2 genotypes in patients with ischemic stroke (IS). Methods: 570 IS patients were randomly assigned to clopidogrel plus aspirin group (n = 284) or aspirin alone group (n = 286). Platelet aggregation and platelet-leukocyte aggregates were measured before and after 7~10 days of treatment. CYP2C19*2 (rs4244285) genotypes were examined using mass spec-trometry. The primary outcome was END during the 10 days of admission. Results: Among the 570 patients, 121 (21.2%) patients suffered from END. Carriers of CYP2C19*2 reduced-function alleles were associated with higher incidence of END (26.8% in carriers vs. 16.6% in noncarriers, P = 0.004). The incidence of END was lower in the clopidogrel plus aspirin group than in the aspirin alone group (17.6 vs. 24.8%, P = 0.032). Stratified analyses revealed that clopidogrel plus aspirin could be more effective in reducing END than aspirin alone for carriers of CYP2C19*2 re-duced-function alleles (18.8 vs. 34.9%, P = 0.006). However, there was no significant difference in incidence of END between dual therapy group and monotherapy group for noncarriers (16.7 vs. 16.6%, P = 0.998). Conclusions: Dual therapy with clopidogrel and aspirin may be adequate for prevention of END in carriers of CYP2C19*2 reduced-function alleles, but not for noncarriers.