Key result
CYP2C19 poor metabolizer status was not significantly associated with 1-year major adverse cardiac and cerebrovascular events in the overall cohort of East Asian patients undergoing percutaneous coronary intervention, although a significant 4-fold increased risk was observed in the acute myocardial infarction subgroup.
Why the study?
The prevalence and influence of CYP2C19 loss-of-function alleles in Southeast Asians receiving clopidogrel remained unclear.
Does the presence of CYP2C19 loss-of-function alleles predict major adverse cardiac and cerebrovascular events in East Asian patients undergoing PCI and receiving clopidogrel?
Cohort (n=999)
No
Does the presence of CYP2C19 loss-of-function alleles predict major adverse cardiac and cerebrovascular events in East Asian patients undergoing PCI and receiving clopidogrel?
Hazard Ratio: 1.6 (95% CI 0.9–2.83)
Absolute Event Rate: 12.1% vs 7.9%
p-value: p=0.108
In East Asian patients presenting with acute myocardial infarction, the CYP2C19 poor metabolizer phenotype is associated with a significantly increased risk of 1-year MACCE and stroke when treated with clopidogrel after PCI.
Supports CYP2C19 testing to guide clopidogrel in East Asian PCI patients; extends evidence on LOF allele risk to this population.
Background: CYP2C19 loss-of-function (LOF) alleles reduce the effectiveness of clopidogrel and are associated with high rates of clinical events in patients undergoing percutaneous coronary intervention (PCI) and stenting in Northeast Asians. However, the prevalence and influence of CYP2C19 LOF alleles in Southeast Asians remain unclear. Objectives: This study aims to retrospectively investigate the prevalence of CYP2C19 LOF alleles and clinical outcomes in East Asian patients taking clopidogrel and undergoing PCI. Methods: Between June 2019 and June 2020, volunteer participants in a single medical center were consecutively selected. The genetic data of CYP2C19 were derived from the Taiwan Precision Medicine Initiative (TPMI). Patients receiving clopidogrel while undergoing PCI with stenting were retrospectively analyzed. Results: A total of 999 patients (62.4 ± 11.1 years old, 83.7% men) were enrolled; 39.3% without the CYP2C19 LOF allele (normal metabolizers + rapid metabolizers, NM + RM); 44.9% with one LOF allele (intermediate metabolizers, IM); 15.7% with two LOF alleles (poor metabolizers, PM). The incidence of stroke was higher in the PM subgroup compared to the NM + RM subgroup or IM subgroup in patients presenting with acute myocardial infarction (AMI). The 1-year major adverse cardiac and cerebrovascular events (MACCE)-free survival rates in all participants were similar among the three groups. However, in the AMI group, the 1-year MACCE-free survival rates were significantly lower in the PM subgroup compared to the NM + RM subgroup or IM subgroup. Conclusion: In East Asians presenting with AMI, CYP2C19 PM was associated with deleterious cardiovascular outcomes and stroke. Our results reinforce the crucial role of preemptive CYP2C19 genotyping in East Asian AMI patients receiving clopidogrel treatment.
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Chen et al. (2022) conducted a cohort in Coronary artery disease undergoing percutaneous coronary intervention with stenting (n=999). CYP2C19 poor metabolizer phenotype vs. Normal and rapid metabolizer phenotypes was evaluated on Major adverse cardiac and cerebrovascular events (MACCE) at 1 year (HR 1.60, 95% CI 0.90-2.83, p=0.108). CYP2C19 poor metabolizer status was not significantly associated with 1-year major adverse cardiac and cerebrovascular events in the overall cohort of East Asian patients undergoing percutaneous coronary intervention, although a significant 4-fold increased risk was observed in the acute myocardial infarction subgroup.
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