经皮冠状动脉介入术后抗血小板个体化治疗的研究

发布时间：2018-05-03 01:29

本文选题：急性冠状动脉综合征 + 经皮冠状动脉介入术　；参考：《青岛大学》2017年硕士论文

【摘要】：目的:观察急性冠状动脉综合征(ACS)患者根据CYP2C19基因型个体化应用抗血小板药物及剂量进行治疗,行经皮冠状动脉介入治疗(PCI)后6个月,对比其血小板反应性和主要心脏不良事件(MACE)及出血事件的发生,为抗血小板药物的个体化治疗提供参考。方法:入选294例ACS患者,根据CYP2C19基因型分为快代谢组(CYP2C19*1/*1)、中代谢组(CYP2C19*1/*2,CYP2C19*1/*3)、慢代谢组(CYP2C19*2/*2,CYP2C19*3/*3,CYP2C19*2/*3),快代谢组给予常规双联抗血小板(氯吡格雷75mg qd+阿司匹林100mg qn)治疗方案,中代谢组给予氯吡格雷剂量加倍(氯吡格雷150mg qd+阿司匹林100mg qn)或用新型抗血小板药物(替格瑞洛90mg bid+阿司匹林100mg qn)治疗方案,慢代谢组给予新型抗血小板药物(替格瑞洛90mg bid+阿司匹林100mg qn)治疗方案,比较各组用药6月后血栓弹力图(TEG)检测血小板抑制率变化情况及MACE的发生情况。结果:294例ACS患者中,携带缺失功能等位基因(CYP2C19*2,CYP2C19*3)的发生比例与既往研究无差别,快代谢型占42.18%、中间代谢型占41.49%,慢代谢型占16.33%。男性中快代谢型占42.26%(101/239),中代谢型占41.84%(100/239),慢代谢型占15.90%(38/239);女性中快代谢型占41.82%(23/55),中代谢型占40.00%(22/55),慢代谢型占18.18%(10/55)。不同性别的基因型分布无统计学意义(P0.05)。根据CYP2C19基因型和个体化抗血小板用药所分组临床基线资料及PCI结果无统计学差异。中代谢型中氯吡格雷加量组、中代谢型中用新型抗血小板药物(替格瑞洛)、慢代谢组用新型抗血小板药物(替格瑞洛)患者用药六个月后血小板抑制率均较常规治疗方案升高,且ADP均大于30%,差别有统计学意义,其中,慢代谢组用新型抗血小板药物(替格瑞洛)的患者和中代谢型组中用新型抗血小板药物(替格瑞洛)的患者ADP抑制率升高较中代谢型组中氯吡格雷加倍组患者明显,且六个月后四组的主要心脏不良事件无统计学意义。结论:携带CYP2C19*2,CYP2C19*3功能缺失基因的高危ACS患者采用氯吡格雷剂量加倍或新型抗血小板药物(替格瑞洛)与无携带CYP2C19*2,CYP2C19*3功能缺失基因的ACS患者采用常规双联抗血小板治疗相比,抗血小板效力和安全性相同。携带CYP2C19*2,CYP2C19*3功能缺失基因的高危患者采用新型抗血小板药物(替格瑞洛)可充分抑制血小板,不增加出血风险,达到无携带缺失等位基因的低危患者水平。CYP2C19基因分型为中代谢型的患者采用新型抗血小板药物(替格瑞洛)或氯吡格雷剂量加倍均可有效抑制血小板反应性,主要心脏不良事件发生率无统计学差异。CYP2C19基因分型中中代谢和慢代谢所占比例较大,按CYP2C19基因分型进行抗血小板药物的个体化治疗很有必要。CYP2C19基因分型可为ACS患者抗血小板药物的选择提供参考。
[Abstract]:Objective: to observe the individual use of antiplatelet drugs and dosage in patients with acute coronary syndrome (ACS) according to CYP2C19 genotypes, 6 months after percutaneous coronary intervention (PCI). The platelet reactivity, major adverse cardiac events (MACEE) and bleeding events were compared in order to provide reference for individualized treatment of antiplatelet drugs. Methods: 294 patients with ACS were divided into two groups according to their CYP2C19 genotypes: fast metabolic group (CYP2C19 / 1 / 1 / 1), middle metabolic group (n = 2) with CYP2C19 / 1 / 1 / 1 / 3, slow metabolic group (n = 3) with CYP2C19 / 2 / 2 / 2 / CYP2C192P / 3, fast metabolic group with routine dual antiplatelet (75mg QAD) 100mg Qnn regimen. In the middle metabolic group, the dosage of clopidogrel was doubled (clopidogrel 150mg QD aspirin 100mg QN) or a new antiplatelet drug (tigrilol 90mg bid aspirin 100mg QN) was used. The slow metabolism group was treated with a new antiplatelet drug (tigrilol 90mg bid aspirin 100mg qnn). The changes of platelet inhibition rate and the incidence of MACE were compared after 6 months of treatment with thromboelastography. Results there was no difference in the incidence of CYP2C192C193with CYP2C192C193in 294 ACS patients. Fast metabolic type accounted for 42.18%, intermediate metabolic type 41.49 and slow metabolic type 16.33%. The rate of rapid metabolism was 42.26% of 101 / 239% in men, 41.84% of 100 / 239%, 15.90% of 38 / 239% of slow metabolic type, 41.82% of 23 / 55% of female metabolic type, 40.002% of 22 / 55% of moderate metabolic type, 18.18% 1055% of slow metabolic type. There was no significant difference in genotype distribution among different genders (P0.05). There was no significant difference in clinical baseline data and PCI results according to CYP2C19 genotypes and individual antiplatelet drug groups. The platelet inhibition rate of the patients treated with clopidogrel in the middle metabolic type, the patients with the new antiplatelet drug (tigrilol) in the middle metabolic type (tigrilol), and the slow metabolism group with the new antiplatelet drug (tigrilol) were all higher than that of the routine treatment regimen. And the ADP is greater than 30, the difference is statistically significant, The inhibition rate of ADP in slow metabolic group was significantly higher than that in clopidogrel double group. There was no significant difference in major adverse cardiac events in the four groups after 6 months. Conclusion: high risk ACS patients with CYP2C192C19C193 deletion gene were treated with double dose clopidogrel or a new antiplatelet drug (tigrilol) compared with ACS patients without CYP2C192CYP2C19C193 deletion gene. Antiplatelet efficacy and safety are the same. High-risk patients with CYP2C192-CYP2C193-deletion gene were treated with a new antiplatelet drug (tigrilol) to fully inhibit platelets without increasing the risk of bleeding. Low risk patients with no deletion alleles. Patients with intermediate metabolic type CYP2C19 genotyped by new antiplatelet drugs (tigrilol) or clopidogrel could effectively inhibit platelet reactivity. There was no statistical difference in the incidence of major adverse cardiac events. In the genotyping of CYP2C19, metabolism and slow metabolism accounted for a large proportion. Individualized treatment of antiplatelet drugs according to CYP2C19 genotyping is very necessary. CYP2C19 genotyping can provide reference for the selection of antiplatelet drugs in ACS patients.
【学位授予单位】：青岛大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R541.4

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