Relationship Between ABCB1 Polymorphisms, Thromboelastography and Risk of Bleeding Events in Clopidogrel-Treated Patients With ST-Elevation Myocardial Infarction
Relationship Between ABCB1 Polymorphisms, Thromboelastography and Risk of Bleeding Events in Clopidogrel-Treated Patients With ST-Elevation Myocardial Infarction
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DOI：
10.1016/j.thromres.2014.08.017
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发表时间：
2014-11-01
影响因子：
7.5
通讯作者：
Yuan, Jin-Qing
中科院分区：
文献类型：
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作者：
Zhang, Jia-Hui;Tang, Xiao-Fang;Yuan, Jin-Qing
简介：本研究旨在探讨 ABCB1 多态性与血栓弹力图（TEG）对接受氯吡格雷治疗的 ST 段抬高型心肌梗死（STEMI）患者出血风险的预测价值之间的关系。方法：连续纳入 467 例接受经皮冠状动脉介入治疗（PCI）的 STEMI 患者。通过连接酶检测反应，检测到ABCB1基因和CYP2C19*2、*3、*17中的20个标签单核苷酸多态性(SNP)。通过 TEG 评估血小板反应性。随访时间为12个月。 结果：通过受试者工作特征曲线分析，ADP抑制的TEG血小板图谱测定值对出血学术研究联盟定义（BARC）≥3b出血的预测价值最佳，曲线下面积（AUC）为0.707（95% CI 0.662-0.749，p = 0.009；截止值>93.4%）。 ADP 抑制还可以预测 BARC >= 3 次出血，AUC 为 0.594（95% CI 0.546-0.640，p = 0.05；临界值 >92.5%）。在调整既定的出血危险因素（包括 CYP2C19*17 等位基因功能获得、年龄、女性、肾功能）后，多变量逻辑回归模型显示 ADP 抑制 >92.5%（OR 2.247，95% CI 1.082-4.665，P = 0.03），携带 rs1045642（OR 2.943，95% CI） 1.195-7.247，P = 0.019）和rs7779562（OR 0.453，95% CI 0.219-0.936，P = 0.032）是BARC = 3次出血的独立预测因子。这些关联在第二组 504 名 STEMI 患者中得到验证。结论：在 PCI 后接受氯吡格雷治疗的 STEMI 患者中，ABCB1 标签 SNP rs1045642 与较高的出血风险相关，而 rs7779562 与较低的出血风险相关，TEG 中的 ADP 抑制具有出血的预测价值。 (C) 2014 Elsevier Ltd. 保留所有权利。
Introduction: This study sought to investigate the relationship of polymorphisms in ABCB1 and the predictive value of thromboelastography (TEG) on bleeding risk in clopidogrel-treated patients with ST-elevation myocardial infarction (STEMI).Methods: 467 consecutive patients with STEMI undergoing percutaneous coronary intervention (PCI) were enrolled. Twenty tag single nucleotide polymorphisms (SNPs) selected from ABCB1 gene and CYP2C19*2, *3, *17 were detected by the ligase detection reaction. Platelet reactivity was assessed by TEG. The follow-up period was 12 months.Results: By receiver operating characteristic curve analysis, the TEG platelet mapping assay value of ADP inhibition had the best predictive value of bleeding academic research consortium definition (BARC) >= 3b bleedings, yielding an area under the curve (AUC) of 0.707 (95% CI 0.662-0.749, p = 0.009; cut-off value >93.4%). ADP inhibition can also predict BARC >= 3 bleedings with an AUC of 0.594 (95% CI 0.546-0.640, p = 0.05; cut-off value >92.5%). After adjustment for established risk factors of bleeding including the gain of function CYP2C19*17 allele, age, female gender, renal function, the multivariable logistic regression model demonstrated that ADP inhibition >92.5% (OR 2.247, 95% CI 1.082-4.665, P = 0.03), carriage of rs1045642 (OR 2.943, 95% CI 1.195-7.247, P = 0.019) and rs7779562 (OR 0.453, 95% CI 0.219-0.936, P = 0.032) were independent predictors of BARC = 3 bleedings. These associations were validated in a second cohort of 504 STEMI patients.Conclusions: In STEMI patients treated with clopidogrel after PCI, the ABCB1 tag SNP rs1045642 is associated with higher risk of bleedings while rs7779562 is associated with lower bleeding risk, and ADP inhibition in TEG has a predictive value of bleedings. (C) 2014 Elsevier Ltd. All rights reserved.