替格瑞洛对糖尿病合并急性冠脉综合征无功能CYP2C19等位基因携带者疗效优于氯吡格雷1例报告及文献复习

IF 0.7 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
AIMS Molecular Science Pub Date : 2022-01-01 Epub Date: 2022-04-28 DOI:10.3934/molsci.2022004
Rahel Tekeste, Gregorio Garza, Song Han, Jianli Dong
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引用次数: 0

摘要

氯吡格雷是一种嘌呤能受体P2Y12 (P2RY12)阻断前药,用于抑制有重大心脏不良事件(MACE)风险的患者的血小板聚集,如冠状动脉疾病和中风。尽管氯吡格雷治疗,一些患者仍可能出现复发性心血管事件。复发的一个可能原因是细胞色素P450 2C19 (CYP2C19)基因的变异。CYP2C19负责包括氯吡格雷在内的许多药物的代谢。最近的研究将CYP2C19变异的药物遗传学检测与氯吡格雷治疗相关,以降低某些复发性mace的风险。通过不同的机制,糖尿病(DM)和肥胖也与氯吡格雷治疗失败有关。我们描述了一名64岁的白人女性,她有急性冠状动脉综合征(ACS)和经皮冠状动脉介入治疗(PCI)的病史,并患有糖尿病/肥胖,她于2019年在接受氯吡格雷/阿司匹林双重抗血小板治疗时因短暂性脑缺血发作(TIA)而向德克萨斯大学医学分部(UTMB)就诊。在CYP2C19基因检测显示为杂合*2基因型的中间代谢物后,替格瑞洛替代氯吡格雷治疗方案。在两年的患者随访中没有记录未来的mace。因此,接受PCI治疗的ACS合并糖尿病/肥胖且CYP2C19代谢为中间代谢的患者,如果使用替格瑞洛代替氯吡格雷,可能会获得更好的治疗效果。这种改善是由于基因型引导治疗还是由于氯吡格雷/替格瑞洛在糖尿病/肥胖患者中的不同相互作用,根据现有数据尚不清楚。无论如何,与标准治疗相比,CYP2C19基因型指导治疗ACS/PCI患者,考虑到糖尿病/肥胖状况,可能提供有效的个体化治疗。将糖尿病/肥胖纳入本研究具有临床意义,因为糖尿病/肥胖已成为美国乃至全世界的主要健康问题。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Ticagrelor is more effective than clopidogrel in carrier of nonfunctional CYP2C19 allele who has diabetes and acute coronary syndrome - case report and literature review.

Clopidogrel is a purinergic receptor P2Y12 (P2RY12)-blocking pro-drug used to inhibit platelet aggregation in patients at risk for major adverse cardiac events (MACE), such as coronary artery disease and stroke. Despite clopidogrel therapy, some patients may still present with recurrent cardiovascular events. One possible cause of recurrence are variants in the cytochrome P450 2C19 (CYP2C19) gene. CYP2C19 is responsible for the metabolism of many drugs including clopidogrel. Recent studies have associated pharmacogenetics testing of CYP2C19 variants to guide clopidogrel therapy with a decreased risk of certain recurrent MACEs. Through a different mechanism, diabetes mellitus (DM) and obesity are also associated with clopidogrel treatment failure. We describe the case of a 64-year-old Caucasian woman with a history of acute coronary syndrome (ACS) and percutaneous coronary intervention (PCI), and DM/obesity, who presented to University of Texas Medical Branch (UTMB) in 2019 with a transient ischemic attack (TIA) while on clopidogrel/aspirin dual anti-platelet therapy. After CYP2C19 genetic testing revealed that she was an intermediate metabolizer with a heterozygous *2 genotype, ticagrelor replaced the clopidogrel treatment regimen. No future MACEs were documented in the two-year patient follow-up. Thus, ACS patients with DM/obesity who have undergone PCI and are intermediate CYP2C19 metabolizers may yield better treatment outcomes if prescribed ticagrelor instead of clopidogrel. Whether this improvement was due to genotype-guided therapy or the differing interactions of clopidogrel/ticagrelor in DM/obese patients is unknown based on available data. Regardless, CYP2C19 genotype-guided treatment of ACS/PCI patients, with consideration of DM/obesity status, may provide effective individualized therapy compared to standard treatment. The inclusion of DM/obesity in this study is clinically relevant because DM/obesity has become a major health issue in the United States and worldwide.

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AIMS Molecular Science
AIMS Molecular Science BIOCHEMISTRY & MOLECULAR BIOLOGY-
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