目的 评价细胞色素P450 2C19(CYP2C19)基因型检测指导冠心病患者经皮冠脉介入治疗(percutaneous coronary intervention,PCI)术后抗血小板治疗的有效性及安全性。方法 选择2013-04至2015-02在武警总医院心内科接受PCI的冠心病患者718例,随机分为研究组和对照组,研究组为进行CYP2C1基因型检测并调整抗血小板药物治疗组,即根据基因型结果快代谢型患者继续口服氯吡格雷75 mg,1次/d、中慢代谢型患者随机调整为氯吡格雷150 mg,1次/d或替格瑞洛90 mg,2次/d;对照组为未检测基因型的常规治疗组,即口服氯吡格雷75 mg,1次/d。观察两组患者术后6个月主要不良心血管事件(MACE事件)和出血事件的发生率。结果 术后6个月MACE事件的发生率研究组(4.7%)显著低于对照组(8.9%),且差异具有统计学意义(P=0.026)。两组出血事件发生率的差异无统计学意义(8.1% vs 6.7%,P=0.475)。结论 对于PCI术后的冠心病患者,进行CYP2C19基因型检测并调整抗血小板药物治疗可减少术后MACE事件的发生,且不增加出血性事件的发生。
Abstract
Objective To evaluate the efficacy and safety of CYP2C19 genotype-guided antiplatelet therapy in patients with coronary artery disease(CAD) after percutaneous coronary intervention(PCI). Methods From April 2013 to February 2015, a total of 718 patients with CAD were admitted and received PCI in the Department of Cardiology, General Hospital of Chinese People’s Armed Police Forces. They were sequentially randomized into study group (n=359) and control group (n=359). In the study group, the CYP2C19 genotypes were detected. The extensive metabolizer (EM) group received clopidogrel 75 mg, qd, the intermediate metabolizer (IM) and poor metabolizer (PM) were randomly assigned to receive either high dose clopidogrel 150 mg, qd or ticagrelor 90mg, bid. The control group routinely received clopidogrel 75 mg, qd. At 6 months, the incidence of major adverse cardiac events (MACE) and bleeding events were observed in the clinical follow up. Results At 6 months follow up, the incidence of MACE in the study group was lower than in the control group (4.7% vs 8.9%,P=0.026). There were no significant difference in the incidence of bleeding events between the two groups(8.1% vs 6.7%,P=0.475). Conclusions In patients with CAD after PCI, CYP2C19 genotype-guided antiplatelet therapy can reduce the incidence of MACE,and does not increase the risk of bleeding event.
关键词
CYP2C19基因 /
氯吡格雷 /
替格瑞洛 /
经皮冠脉介入治疗 /
主要心血管不良事件
Key words
cytochrome 2C19 /
clopidogrel /
ticagrelor /
percutaneous coronary intervention /
major adverse cardiovascular events
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参考文献
[1] Yusuf S, Zhao F, Mehta S R, et al. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation[J]. N Engl J Med, 2001, 345(23):494-502.
[2] Bliden K P, Dichiara J, Tantry U S, et al. Increased risk in patients with high platelet aggregation receiving chronic clopidogrel therapy undergoing percutaneous coronary intervention: is the current antiplatelet therapy adequate? [J]. J Am Coll Cardiol, 2007, 49(6):657-666.
[3] 石红婷,周伯荣,王 融.缺血性卒中患者氯吡格雷抵抗的危险因素:前瞻性病例系列研究[J]. 国际脑血管病杂志, 2012, 20(6):423-427.
[4] 孙亚勤,杨胜利,黄 洁.CYP2C19基因多态性和氯吡格雷抵抗对冠心病介入术预后的影响[J]. 武警医学, 2015, 26(8):858-862.
[5] Savi P, Pereillo J M, Uzabiaga M F, et al. Identification and biological activity of the active metabolite of clopidogrel[J]. Thromb Haemost, 2000, 84(5):891-896.
[6] Hollopeter G, Jantzen H M, Vincent D, et al. Identification of the platelet ADP receptor targeted by antithrombotic drugs[J]. Nature, 2001, 409(6817):202-207.
[7] Uchiyama S. Clopidogrel resistance: identifying and overcoming a barrier to effective antiplatelet treatment[J]. Cardiovasc Ther, 2011, 29(6):e100-111.
[8] 梁 艳,刘振华,白清清. CYP2C19基因型与奥美拉唑治疗消化道溃疡疗效的相关性[J]. 武警医学, 2014, 25(2):142-147.
[9] Lee J M, Park S, Shin D J, et al. Relation of genetic polymorphisms in the cytochrome P450 gene with clopidogrelresistance after drug-eluting stent implantation in Koreans[J]. Am J Cardiol,2009,104(1):46-51.
[10] FDA Drug Safety Communication: reduced effectiveness of Plavix (clopidogrel) in patients who are poor metabolizers of the drug. http://www.fda.gov/Drugs/ Drug Safety/Postmarket Drug Safety Information for Patients and Providers/ucm190836.htm (accessed 3 Aug 2010).
[11] Sibbing D, Stegherr J, Latz W, et al. Cytochrome P450 2C19 loss-of-function polymorphism and stent thrombosis following percutaneous coronary intervention[J].Eur Heart J, 2009, 30(8):916-922.
[12] 张卫华, 唐发宽, 林乐健, 等. CYP2C19基因型功能缺失患者介入术后氯吡格雷剂量与心脏不良事件相关性研究[J].中华老年心脑血管病杂志, 2013, 15(10):1041-1043.
[13] Husted S, Giezen J J. Ticagrelor: the first reversibly binding oral P2Y12 receptor antagonist[J]. Cardiovasc Ther,2009,27(4):259-274.
[14] 吴 丹,杨胜利,路 靖,等.冠心病患者支架术后根据检测药物代谢酶CYP2C19基因调整抗血小板治疗的价值[J]. 中国循环杂志, 2015, 30(3):216-219.
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