Derivation, Validation, and Prognostic Utility of a Prediction Rule for Nonresponse to Clopidogrel The ABCD-GENE Score
Derivation, Validation, and Prognostic Utility of a Prediction Rule for Nonresponse to Clopidogrel The ABCD-GENE Score
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DOI：
10.1016/j.jcin.2020.01.226
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发表时间：
2020-03-09
影响因子：
11.3
通讯作者：
Price, Matthew J.
中科院分区：
文献类型：
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作者：
Angiolillo, Dominick J.;Capodanno, Davide;Price, Matthew J.
本研究的目的是开发一种风险评分，将细胞色素P450 2C 19功能丧失基因型与影响氯吡格雷反应的临床风险因素相结合，从而更精确地识别高血小板反应性（HPR）和不良临床结局的风险受试者。然而，相当多的患者实现血小板抑制不足，持续HPR，血栓形成风险增加的一个既定标志物，强调需要工具来帮助识别这些受试者。虽然细胞色素P450 2C 19酶的功能丧失等位基因的携带者降低了氯吡格雷的代谢，导致HPR和血栓并发症的发生率增加，但这只能解释氯吡格雷药效学反应的一小部分，而且许多临床因素也被证明具有促进作用。1）开发一个综合遗传和临床因素的风险评分，以识别使用氯吡格雷时发生HPR的患者; 2）调查风险评分的外部效度;和3）定义与使用氯吡格雷治疗的心肌梗死患者队列中的风险评分相关的临床结局。（年龄、体重指数、慢性肾脏病、糖尿病和基因分型）合并了5个独立的HPR预测因子：4个临床（年龄>75岁、体重指数>30 kg/m2）、慢性肾脏病[肾小球滤过率= 10]与识别HPR状态的最佳敏感性和特异性相关。1年时，全因死亡评分的C统计量为0.67（95% CI：0.64 - 0.71），全因死亡、卒中或心肌梗死复合评分的C统计量为0.66（95% CI：0.63 - 0.69）。使用多个模型进行校正，ABCD-GENE评分与全因死亡以及全因死亡、中风或心肌梗死的复合事件一致且独立相关，两者均作为连续变量并使用>= 10的截止值。该分数并没有预测bleeding.CONCLUSIONS的ABCD-GENE评分是一个简单的工具，以确定患者与HPR氯吡格雷和谁是在急性心肌梗死后的不良缺血事件，包括死亡率的风险增加。在ABCD-GENE评分较高的患者中，应考虑长期口服氯吡格雷以外的P2 Y12抑制剂。(C)2020年由美国心脏病学会基金会。
OBJECTIVES The aim of this study was to develop a risk score integrating cytochrome P450 2C19 loss-of-function genotypes with clinical risk factors influencing clopidogrel response that would allow the identification with more precision of subjects at risk for high platelet reactivity (HPR) and adverse clinical outcomes.BACKGROUND Clopidogrel is the most broadly used platelet P2Y(12) inhibitor. However, a considerable number of patients achieve inadequate platelet inhibition, with persistent HPR, an established marker of increased thrombotic risk, underscoring the need for tools to help identify these subjects. Although carriers of loss-of-function alleles of the cytochrome P450 2C19 enzyme have reduced clopidogrel metabolism leading to increased rates of HPR and thrombotic complications, this explains only a fraction of the pharmacodynamic response to clopidogrel, and a number of clinical factors have also been shown to have contributing roles.METHODS Three prospective and independent studies were used to: 1) develop a risk score integrating genetic and clinical factors to identify patients with HPR while on clopidogrel; 2) investigate the external validity of the risk score; and 3) define clinical outcomes associated with the risk score in a cohort of patients with myocardial infarction treated with clopidogrel.RESULTS A risk score ABCD-GENE (Age, Body Mass Index, Chronic Kidney Disease, Diabetes Mellitus, and Genotyping) was developed incorporating 5 independent predictors of HPR: 4 clinical (age >75 years, body mass index >30 kg/m(2), chronic kidney disease [glomerular filtration rate= 10 was associated with the best sensitivity and specificity to identify HPR status. The C-statistics for the score were 0.67 (95% CI: 0.64 to 0.71) for all-cause death and 0.66 (95% CI: 0.63 to 0.69) for the composite of all-cause death, stroke, or myocardial infarction at 1 year. Using multiple models for adjustment, the ABCD-GENE score consistently and independently correlated with all-cause death, as well as with the composite of all-cause death, stroke, or myocardial infarction, both as a continuous variable and by using the cutoff of >= 10. The score did not predict bleeding.CONCLUSIONS The ABCD-GENE score is a simple tool to identify patients with HPR on clopidogrel and who are at increased risk for adverse ischemic events, including mortality, following an acute myocardial infarction. In patients with a high ABCD-GENE score, long-term oral P2Y12 inhibitors other than clopidogrel should be considered. (C) 2020 by the American College of Cardiology Foundation.