不同CYP2C19基因型糖尿病合并急性冠脉综合征患者抗血小板策略及对预后的影响

Effect of antiplatelet strategy on prognosis of in patients with diabetes mellitus and acute coronary syndrome with different CYP2C19 genotype

目的探讨有无携带CYP2C19功能缺陷(LOF)基因的糖尿病(DM)合并急性冠脉综合征(ACS)患者选择不同P2Y12抑制剂对其远期预后的影响。方法选择266例接受经皮冠状动脉介入治疗(PCI)的ACS患者。对患者进行CYP2C19基因多态性检测,按照携带CYP2C19 LOF基因的情况,分成快代谢型(未携带CYP2C19 LOF基因)和中慢代谢型(携带CYP2C19 LOF基因);按照有无DM分为A组和B组;按照患者PCI术后选择的P2Y12血小板抑制剂类型,分为替格瑞洛亚组和氯吡格雷亚组。记录各亚组3年内的MACE事件,分析患者CYP2C19 LOF基因型和所用P2Y12类型对其预后的影响。结果快代谢型患者在PCI术后的3年中,各亚组间的MACE、再次血运重建、卒中、心衰再住院、主要出血、全因死亡率均无显著差异(均P>0.05)。在中慢代谢型患者中,使用替格瑞洛可显著减低MACE事件发生、心脏再次血运重建的概率(均P<0.01);可显著降低DM患者的心梗再次发生率。结论快代谢型DM合并ACS患者在PCI术后选择不同的P2Y12抑制剂对其预后无明显影响;对于中慢代谢型DM合并ACS患者,替格瑞洛不仅可以显著降低MACE、再次血运重建及再次心梗的发生率,同时未增加主要出血的风险;在减少再次心梗方面,DM患者使用替格瑞洛的获益比非DM患者更大。

Objective To investigate the effect of different P2Y12 inhibitors on the long-term prognosis of patients with diabetes mellitus(DM)and acute coronary syndrome(ACS),with or without the CYP2C19 loss-of-function(LOF)gene.Method 266 consecutive ACS patients undergoing percutaneous coronary intervention(PCI)were enrolled.According to the CYP2C19 LOF genotype,the patients were divided into rapid metabolizing-type(without the CYP2C19 LOF gene)and moderate-slow metabolizing type(with the CYP2C19 LOF gene).Each type was divided into the A group(with diabetes)and the B group(without diabetes).Each group was divided into the ticagrelor subgroup and the clopidogrel subgroup according to the type of P2Y12 platelet inhibitor.The MACE events were recorded for each subgroup over 3 years,and the prognostic impact of the CYP2C19 LOF genotype and the type of P2Y12 used were analyzed.Results There were no significant differences in MACE,revascularization,stroke,heart failure rehospitalization,major bleeding,or all-cause mortality among subgroups of patients with rapid metabolizing type at 3 years after PCI(all P>0.05).In patients with moderate-slow metabolizing-type,the use of tegretol significantly reduced the probability of MACE events and cardiac revascularization(all P<0.01)and significantly reduced the reoccurrence of heart attack in patients with DM.Conclusions In DM combined with ACS patients with rapid metabolizing type,the choice of different P2Y12 inhibitors after PCI had no significant effect on their prognosis.In DM combined with ACS patients with moderate-slow metabolizing type,tegretol not only significantly reduced the incidence of MACE,revascularization,and reinfarction,but also did not increase the risk of major bleeding.In terms of reducing the reoccurrence of heart attack,the benefit of using tegretol in the DM patients was greater than in the non-DM patients.