CYP2C19基因多态性对氯吡格雷和替格瑞洛治疗急性冠脉综合征患者疗效的影响

The Effect of CYP2C19 gene Polymorphisms on Outcomes of Treatment with Ticagrelor Versus Clopidogrel for Acute Coronary Syndromes

目的明确CYP2C19基因多态性对采用氯吡格雷和替格瑞洛治疗的急性冠脉综合征(ACS)患者疗效的影响。方法纳入2011年12月至2013年12月行经皮冠脉介入治疗(PCI)的ACS患者280例。根据CYP2C19基因型分析结果及治疗的药物,分为氯吡格雷快代谢组(n=74)、氯吡格雷中代谢组(n=140)、氯吡格雷慢代谢组(n=33)及替格瑞洛慢代谢组(n=33)。在服药前及服药后不同时间点对患者的凝血酶原时间(PT)、活化的部分凝血酶原时间(a PTT)、纤维蛋白原(Fbg)浓度进行检测,同时检测患者的血小板抑制率。并对患者随访期间的主要终点事件的发生情况进行分析。结果服药前、服药后1月、6月和12月时,四组患者在PT、a PTT、Fbg等凝血指标上均无显著差异(P>0.05)。替格瑞洛在服药后1月、6月和12月时均能有效降低慢代谢型ACS患者ADP抑制率(全部P<0.05),而氯吡格雷只在服药后的6月和12月时才能有效降低慢代谢型ACS患者ADP抑制率(两个时间点P<0.05)。另外,在服药后1月、6月及12月时,替格瑞洛对ADP的有效降低率显著高于氯吡格雷处理组(P<0.05)。随访结果显示:相比于氯吡格雷治疗组,替格瑞洛治疗能够有效降低慢代谢型ACS患者心血管事件的发生率。结论相比于氯吡格雷,替格瑞洛能够更加有效降低CYP2C19慢代谢型ACS患者的ADP抑制率、PCI术后1月及6月时支架血栓的形成率及心血管事件的发生率。

Objective The aim of this study was to investigate the effect of CYP2C19 gene polymor- phism on outcomes of treatment with tricagrelor versus clopidogrel for acute coronary syndromes （ACS）. Meth- ods A total of 280 patients with ACS who were underwent percutaneous coronary intervention were includ- ed. The patients were grouped into clopidogrel poor metabolizers （ PM, n = 74 ）, clopidogrel intermediate mc- tabolizers （ IM, n = 140）, clopidogrel extensive metabolizers （ EM, n = 33 ） and ticagrelor extensive metabolizers （EM, n = 33 ）according to the CYP2C19 genetype and treatment. The prothrombin time（ PT）, activated partial thromboplastin time（aprFF） ,fibrinogen（Fbg） and platelet inhibition rate were measured in all patients at spe- cific time point. The major endpoint events also recorded. Results We observed no significant difference on the FF, aPTT and Fbg among between PM patient treated clopidogrel and ticagrelor. A significant inhibition of platelet aggregation was found at 1,6 and 12 month posttreatment in ticagrelor group（ allP 〈 0.05 ）while sig- nificant inhibition of platelet aggregation was found at 6 and 12 month posttreatment in clopidogrel group （ bothP 〈 0. 05 ）. In addition, a significant difference was found on platelet inhibition between clopidogrel and ticagrelor at 1,6 and 12 months posttreatment（ all P 〈 0.05 ）. The follow up data showed that ticagrelor could significant reduced the incidence of cardiovascular events comparing with the clopidogrel treat- ment. Conclusion Comparing with the clopidogrel, ticagrelor can effectively inhibit platelet aggregation, re- duce the rsik of 1 month and 6 month stent thrombosis, and decrease the incidence of cardiovascular events at 1 year follow-up in PM patients.