Pharmacogenetic and clinical predictors of response to clopidogrel plus aspirin after acute coronary syndrome in Egyptians.
Pharmacogenetic and clinical predictors of response to clopidogrel plus aspirin after acute coronary syndrome in Egyptians.
复制标题
埃及人急性冠状动脉综合征后，对氯吡格雷和阿司匹林反应的药物遗传学和临床预测指标。
DOI：
10.1097/fpc.0000000000000349
复制
发表时间：
2018-09
影响因子：
2.6
通讯作者：
Cavallari, Larisa H.
中科院分区：
文献类型：
--
作者：
Fathy, Shaimaa;Shahin, Mohamed H.;Langaee, Taimour;Khalil, Basma M.;Saleh, Ayman;Sabry, Nagwa A.;Schaalan, Mona F.;El Wakeel, Lamiaa L.;Cavallari, Larisa H.
阿司匹林和氯吡格雷双重抗血小板治疗（DAPT）可降低急性冠脉综合征（ACS）后心血管事件复发的风险。然而，对DAPT的反应存在显著差异，可能受到遗传和非遗传因素的影响。本研究旨在评估PON 1、PEAR-1、P2 Y12、CES 1和CYP 2C 19沿着临床、人口统计学和社会因素的遗传多态性对埃及人DAPT反应变异的影响。本研究纳入了230例埃及患者，在首次ACS后接受氯吡格雷75 mg/d和阿司匹林81 mg/d治疗至少12个月。进行简单和多变量logistic回归分析，以确定与氯吡格雷治疗受试者的主要不良心血管事件（MACE）相关的因素，MACE定义为ACS复发、缺血性卒中、支架相关血运重建或死亡的发生。多因素Logistic回归分析显示，CYP 2C 19 *2基因多态性是MACE的唯一遗传预测因子[比值比（OR）：2.23，95%可信区间（CI）：1.15-4.33，P=0.01]。此外，质子泵抑制剂（PPI）的使用（OR 4.77，95% CI：1.47 - 15.54，p=0.009）和糖尿病（OR 1.83，95%CI：1.03 - 3.26，p=0.03）与较高的心血管风险相关，而他汀类药物使用与较低的风险相关。（OR 0.43，95% CI：0.25 - 0.76，p=0.003）。这四种遗传和非遗传因素的贡献解释了接受DAPT治疗的埃及人MACE风险变异性的19%。这些结果强调，CYP 2C 19 *2、沿着糖尿病以及PPI和他汀类药物的使用是与埃及人ACS后DAPT临床应答变异性相关的重要因素。
Dual antiplatelet therapy (DAPT) with aspirin and clopidogrel reduces the risk for recurrent cardiovascular events after acute coronary syndrome (ACS). However, there is significant variation in response to DAPT that may be influenced by both genetic and non-genetic factors. This study aimed to assess the effect of genetic polymorphisms in PON1, PEAR-1, P2Y12, CES1 and CYP2C19 along with clinical, demographic, and social factors, on variation in response to DAPT in Egyptians. This study included 230 Egyptian patients treated with clopidogrel 75 mg/day and aspirin 81 mg/day for at least 12 months following their first ACS. Simple and multivariable logistic regression analysese were carried out to identify factors associated with major adverse cardiovascular events (MACE), defined as the occurrence of recurrent ACS, ischemic stroke, stent-related revascularization, or death, in clopidogrel-treated participants. Using multivariable logistic regression analysis, the CYP2C19*2 polymorphism was the only genetic predictor of MACE [odds ratio (OR): 2.23, 95% confidence interval (CI): 1.15–4.33, P=0.01]. In addition, proton pump inhibitor (PPI) use (OR 4.77, 95% CI: 1.47 – 15.54, p=0.009) and diabetes (OR 1.83, 95% CI: 1.03 – 3.26, p=0.03) were associated with higher cardiovascular risk, while statin use was associated with lower risk (OR 0.43, 95% CI: 0.25 – 0.76, p=0.003). The contribution of these four genetic and non-genetic factors explained 19% of the variability in risk for MACE in Egyptians treated with DAPT. These results highlight that CYP2C19*2, along with diabetes, and use of PPI and statins are important factors jointly associated with variability in clinical response to DAPT following ACS in Egyptians.