Liao Yi-Ju, Hsiao Tzu-Hung, Lin Ching-Heng, Hsu Chun-Sheng, Chang Yen-Lin, Chen Yu-Wei, Hsu Chiann-Yi, Chen Yi-Ming, Wu Ming-Fen
Department of Pharmacy, Taichung Veterans General Hospital, Taichung, Taiwan.
Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan.
Pharmgenomics Pers Med. 2022 Feb 2;15:81-89. doi: 10.2147/PGPM.S335860. eCollection 2022.
Clopidogrel is widely used in coronary artery, peripheral arterial, and cerebrovascular disease. We aimed to study the association of the CYP2C19 phenotype with cardiovascular outcomes and interventional procedures in a hospital-based population.
This cross-sectional, retrospective study enrolled patients with prior exposure to clopidogrel at the Taichung Veterans General Hospital (TCVGH) using data extracted from the Taiwan Precision Medicine Initiative (TPMI). Data on the CYP2C19 phenotype, drug-prescription profile, comorbidities, vascular intervention procedures, and hospitalization due to acute myocardial infarction (AMI) or stroke of clopidogrel users were analyzed.
From the 32,728 patients in the TCVGH-TPMI cohort, we selected 2687 clopidogrel users. A total of 400 (14.9%) clopidogrel poor metabolizers (PMs), 1235 (46.0%) intermediate metabolizers (IMs), and 1052 (39.2%) extensive metabolizers (EMs) were identified. The predominant loss-of-function allele is *2. In 2687 patients with clopidogrel exposure, the CYP2C19 PM phenotype was unassociated with hospitalization due to AMI or stroke after adjusting for comorbidities and carotid angiographies. Among the 1554 clopidogrel users who underwent cardiovascular intervention, 193 (12.4%) received two or more types of interventional procedures. Compared with non-PMs, patients with the PM phenotype had a higher risk of multiple carotid interventions (OR: 3.13, 95% CI: 1.19-8.22).
In this hospital-wide cohort, 8.2% were clopidogrel users, of which 14.9% were CYP2C19 PMs. The result of this study does not support universal genotyping of CYP2C19 in all clopidogrel users to identify risks for stroke and AMI. CYP2C19 PMs are more likely to undergo multiple carotid interventions than non-PMs. Prospective studies to investigate the association of the CYP2C19 genotype and carotid interventions and outcomes are needed to validate our results.
氯吡格雷广泛应用于冠状动脉疾病、外周动脉疾病和脑血管疾病。我们旨在研究在以医院为基础的人群中,CYP2C19基因表型与心血管结局及介入治疗的相关性。
本横断面回顾性研究纳入了台中荣民总医院(TCVGH)中曾使用过氯吡格雷的患者,数据来自台湾精准医疗计划(TPMI)。分析了氯吡格雷使用者的CYP2C19基因表型、药物处方情况、合并症、血管介入治疗及因急性心肌梗死(AMI)或中风住院的数据。
在TCVGH-TPMI队列的32728例患者中,我们选取了2687例氯吡格雷使用者。共识别出400例(14.9%)氯吡格雷慢代谢者(PMs)、1235例(46.0%)中间代谢者(IMs)和1052例(39.2%)快代谢者(EMs)。主要的功能缺失等位基因为*2。在2687例曾使用氯吡格雷的患者中,调整合并症和颈动脉血管造影后,CYP2C19基因PM表型与因AMI或中风住院无关。在1554例接受心血管介入治疗的氯吡格雷使用者中,193例(12.4%)接受了两种或更多类型的介入治疗。与非PMs相比,PM表型患者接受多次颈动脉介入治疗的风险更高(OR:3.13,95%CI:1.19-8.22)。
在这个全院队列中,8.2%的患者使用氯吡格雷,其中14.9%为CYP2C19基因PMs。本研究结果不支持对所有氯吡格雷使用者进行CYP2C19基因普遍分型以识别中风和AMI风险。与非PMs相比,CYP2C19基因PMs更有可能接受多次颈动脉介入治疗。需要进行前瞻性研究以调查CYP2C19基因与颈动脉介入治疗及结局的相关性,从而验证我们的结果。