两种他汀类药物对不同细胞色素P450酶2C19基因型患者氯吡格雷抗血小板作用的影响

目的观察2种他汀类药物对不同细胞色素P450酶(CYP)2C19基因型的急性冠状动脉综合征(ACS)患者氯吡格雷抗血小板作用的影响。方法选取接受CYP2C19基因型检测的老年ACS患者200例,根据服用他汀类药物及CYP2C19基因型分为6组:阿托伐他汀+快代谢组(A组)40例,瑞舒伐他汀+快代谢组(B组)40例;阿托伐他汀+中代谢组(C组)46例,瑞舒伐他汀+中代谢组(D组)46例;阿托伐他汀+慢代谢组(E组)14例,瑞舒伐他汀+慢代谢组(F组)14例。在使用氯吡格雷前(基线)、联合服用他汀类药物前(治疗前)及服用他汀类药物7 d(治疗后),测定二磷酸腺苷诱导的血小板聚集率;随访6个月,观察主要不良心血管事件(MACE)的发生率。结果与基线比较,治疗前和治疗后A组、B组、C组、D组、E组和F组血小板聚集率明显降低(P<0.05),且治疗后较治疗前更低[(3.9±0.2)%vs(5.2±0.3)%;(3.8±0.2)%vs(5.3±0.3)%;(4.9±0.4)%vs(5.3±0.3)%;(5.0±0.3)%vs(5.1±0.4)%;(5.0±0.4)%vs(5.2±0.3)%;(4.9±0.5)%vs(5.1±0.4)%,P<0.05];治疗后在相同基因代谢类型中,A组与B组、C组与D组、E组与F组血小板聚集率比较,无统计学差异(P>0.05);治疗后在不同基因代谢类型中,A组血小板聚集率明显低于C组和E组(P<0.05),B组血小板聚集率明显低于D组和F组,差异有统计学意义(P<0.05);C组与E组,D组与F组血小板聚集率比较,差异无统计学意义(P>0.05)。6组MACE发生率比较,差异无统计学意义(P>0.05)。结论2种他汀类药物对于同一代谢基因型组氯吡格雷抗血小板活性没有影响,对于不同代谢基因型患者氯吡格雷抗血小板活性有影响,氯吡格雷抗血小板活性受到CYP2C19基因多态性的影响。

Effect of two statins on antiplatelet activity of clopidogrel in elderly acute coronary syndrome patients with different CYP2C19 genotypes

Objective To study the effect of two statins on antiplatelet activity of clopidogrel in elderly acute coronary syndrome(ACS)patients with different CYP2C19 genotypes.Methods Two hundred elderly ACS patients who underwent detection of CYP2C19 genotypes in our hospital were divided into group A(n=40),group B(n=40),group C(n=46),group D(n=46),group E(n=14),group F(n=14)accroding to the types of statins they took and CYP2C19 genotypes.The ADP-induced platelet aggregation was detected before treatment with clopidogrel and statins and after 7 days of treatment with statins.The patients were followed up for 6 months,during which the incidence of MACE was recorded.Results The platelet aggregation rate was significantly lower in groups A-F before and after treatment than before treatment with clopidogrel(P<0.05)and after treatment than before treatment(3.9%±0.2%vs 5.2%±0.3%,3.8%±0.2%vs 5.3%±0.3%,4.9%±0.4%vs 5.3%±0.3%,5.0%±0.3%vs 5.1%±0.4%,5.0%±0.4%vs 5.2%±0.3%,4.9%±0.5%vs 5.1%±0.4%,P<0.05).No significant difference was detected in platelet aggregation rate between group A and groups B-F after treatment(P>0.05).The platelet aggregation rate was significantly lower in group A than in groups C and E(P<0.05)and in group B than in groups D and F(P<0.05).No significant difference was detected in platelet aggregation rate between groups C and E,between groups D and F(P>0.05),and in incidence of MACE in groups A-F(P>0.05).Conculsion The two statins do not affect the antiplatelet activity of clopidogrel in ACS patients with the same CYP2C19 genotypes,but affect the antiplatelet activity of clopidogrel in ACS patients with different CYP2C19 genotypes.The antiplatelet activity of clopidogrel can be affected by CYP2C19 gene polymorphonism.