抗血小板治疗临床决策中的遗传学因素
Genetics in the Clinical Decision of Antiplatelet Treatment.
作者信息
Siasos Gerasimos, Zaromitidou Marina, Oikonomou Evangelos, Vavuranakis Manolis, Tsigkou Vicky, Papageorgiou Nikolaos, Chaniotis Dimitrios, Vrachatis Dimitrios A, Stefanadis Christodoulos, Papavassiliou Athanasios G, Tousoulis Dimitrios
机构信息
Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School and Harvard-MIT Biomedical Engineering Center, Massachusetts Institute of Technology, Boston, MA, United States.
出版信息
Curr Pharm Des. 2017;23(9):1307-1314. doi: 10.2174/1381612822666161226152529.
BACKGROUND
Coronary artery disease remains the leading cause of death globally. Dual antiplatelet treatment with aspirin and aP2Y12 receptor significantly reduces thrombotic events. However, antiplatelet drug response displays considerable interindividual variability.
METHODS
Genetic factors account for up to 70% of impaired drug response. A number of genes encoding proteins involved in the pharmacokinetic pathway have been found to alter drug response.
RESULTS
According to most studies, CYP2C19 gene is the strongest genetic determinant. The novel antiplatelet agents prasugrel and ticagrelor, seem to overcome genetic restrictions but in expense of increased bleeding rates. Achieving a balance between adequate platelet inhibition and bleeding complications is challenging.
CONCLUSION
Genetic screening may provide valuable guidance towards an efficient antiplatelet treatment. However, the lack of randomized controls trials testing the effect of a genotype-guided therapy, forbids the implementation of genetic testing into clinical practice.
背景
冠状动脉疾病仍是全球主要的死亡原因。阿司匹林和P2Y12受体双重抗血小板治疗可显著减少血栓形成事件。然而，抗血小板药物反应存在相当大的个体差异。
方法
遗传因素占药物反应受损的比例高达70%。已发现许多参与药代动力学途径的蛋白质编码基因会改变药物反应。
结果
根据大多数研究，CYP2C19基因是最强的遗传决定因素。新型抗血小板药物普拉格雷和替格瑞洛似乎克服了遗传限制，但代价是出血率增加。在充分的血小板抑制和出血并发症之间取得平衡具有挑战性。
结论
基因筛查可为有效的抗血小板治疗提供有价值的指导。然而，缺乏测试基因型指导疗法效果的随机对照试验，禁止将基因检测应用于临床实践。
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