Clopidogrel Use and CYP2C19 Genotypes in Patients Undergoing Vascular Intervention Procedure: A Hospital-Based Study

Yi-Ju Liao; Tzu-Hung Hsiao; Ching-Heng Lin; Chun-Sheng Hsu; Yen-Lin Chang; Yu-Wei Chen; Chiann-Yi Hsu; Yi-Ming Chen; Ming-Fen Wu

doi:10.2147/PGPM.S335860

Clopidogrel Use and CYP2C19 Genotypes in Patients Undergoing Vascular Intervention Procedure: A Hospital-Based Study

Pharmgenomics Pers Med. 2022 Feb 2:15:81-89. doi: 10.2147/PGPM.S335860. eCollection 2022.

Authors

Yi-Ju Liao¹, Tzu-Hung Hsiao^{2

3

4}, Ching-Heng Lin^{2

3

5

6}, Chun-Sheng Hsu^{7

8

9

10}, Yen-Lin Chang^{1

8}, Yu-Wei Chen¹¹, Chiann-Yi Hsu^{2

12}, Yi-Ming Chen^#^{2

10

13

14

15}, Ming-Fen Wu^#¹

Affiliations

¹ Department of Pharmacy, Taichung Veterans General Hospital, Taichung, Taiwan.
² Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan.
³ Department of Public Health, Fu Jen Catholic University, New Taipei City, Taiwan.
⁴ Institute of Genomics and Bioinformatics, National Chung Hsing University, Taichung, Taiwan.
⁵ Institute of Public Health and Community Medicine Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan.
⁶ Department of Industrial Engineering and Enterprise Information, Tunghai University, Taichung, Taiwan.
⁷ Department of Physical Medicine and Rehabilitation, Taichung Veterans General Hospital, Taichung, Taiwan.
⁸ Department of Public Health and Institute of Public Health, Chung Shan Medical University, Taichung, Taiwan.
⁹ School of Medicine, National Defense Medical Center, Taipei, Taiwan.
¹⁰ Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan.
¹¹ Cardiovascular Center, Taichung Veterans General Hospital, Taichung, Taiwan.
¹² Biostatistics Task Force of Taichung Veterans General Hospital, Taichung, Taiwan.
¹³ Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
¹⁴ Rong Hsing Research Center for Translational Medicine & Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung, Taiwan.
¹⁵ School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.

^# Contributed equally.

Abstract

Purpose: 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.

Patients and methods: 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.

Results: 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).

Conclusion: 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.

Keywords: CYP2C19; TPMI; Taiwan precision medicine initiative; carotid intervention; clopidogrel; pharmacogenomics.