Key result
CYP2C19 poor metabolizer phenotype linked to ~213% greater risk of multiple carotid interventions vs non-PMs.
Why the study?
The association of the CYP2C19 phenotype with cardiovascular outcomes and vascular interventions in clopidogrel users was unclear in a hospital-based population.
Does the CYP2C19 poor metabolizer phenotype increase the risk of hospitalization for AMI or stroke in patients treated with clopidogrel?
Cross-Sectional (n=2,687)
No
Does the CYP2C19 poor metabolizer phenotype increase the risk of hospitalization for AMI or stroke in patients treated with clopidogrel?
Odds Ratio: 3.13 (95% CI 1.19–8.22)
In a Taiwanese hospital cohort, the CYP2C19 poor metabolizer phenotype was not associated with increased hospitalization for AMI or stroke among clopidogrel users, suggesting universal genotyping may not be warranted.
CYP2C19 poor metabolizer phenotype was associated with higher multiple carotid intervention risk; hypothesis-generating and should not yet change clopidogrel practice.
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.
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A 2022 study conducted a cross-sectional in Prior exposure to clopidogrel (n=2,687). CYP2C19 poor metabolizer (PM) phenotype vs. Non-poor metabolizers (non-PMs) was evaluated on Multiple carotid interventions (OR 3.13, 95% CI 1.19-8.22). Compared with non-PMs, patients with the CYP2C19 poor metabolizer phenotype had a higher risk of multiple carotid interventions (OR 3.13; 95% CI 1.19-8.22).
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