Tekeste Rahel, Garza Gregorio, Han Song, Dong Jianli
School of Medicine, University of Texas Medical Branch, Galveston, TX, USA.
Health Sciences Division, University of Monterrey, Monterrey, NL, Mexico.
AIMS Mol Sci. 2022;9(2):66-78. doi: 10.3934/molsci.2022004. Epub 2022 Apr 28.
Clopidogrel is a purinergic receptor ()-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 () gene. is responsible for the metabolism of many drugs including clopidogrel. Recent studies have associated pharmacogenetics testing of 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 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 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, 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.
氯吡格雷是一种嘌呤能受体（）阻断前体药物，用于抑制有重大不良心脏事件（MACE）风险的患者（如冠状动脉疾病和中风患者）的血小板聚集。尽管接受了氯吡格雷治疗，但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（）基因的变异。负责包括氯吡格雷在内的许多药物的代谢。最近的研究将检测变异体的药物遗传学检测与指导氯吡格雷治疗、降低某些复发性MACE的风险联系起来。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岁的白人女性病例，她有急性冠状动脉综合征（ACS）和经皮冠状动脉介入治疗（PCI）病史，同时患有DM/肥胖症，2019年在服用氯吡格雷/阿司匹林双联抗血小板治疗期间因短暂性脑缺血发作（TIA）就诊于德克萨斯大学医学分校（UTMB）。基因检测显示她是一名杂合子*2基因型的中间代谢者后，替格瑞洛取代了氯吡格雷治疗方案。在对该患者进行的两年随访中，未记录到未来的MACE。因此，对于接受过PCI且为中间代谢者的DM/肥胖ACS患者，开具替格瑞洛而非氯吡格雷可能会产生更好的治疗效果。根据现有数据，尚不清楚这种改善是由于基因型指导的治疗还是替格瑞洛/氯吡格雷在DM/肥胖患者中的不同相互作用。无论如何，与标准治疗相比，考虑DM/肥胖状态对ACS/PCI患者进行基因型指导的治疗可能会提供有效的个体化治疗。本研究纳入DM/肥胖具有临床相关性，因为DM/肥胖已成为美国和全球的一个主要健康问题。
