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CYP2C19 Genetic Variants Associated with Clopidogrel Resistance and Major Adverse Cardiovascular Events in Vietnamese
Toan Nguyen Duy1, Oanh Nguyen Oanh1, Kien Nguyen Trung2
1Cardiovascular Center, Military Hospital 103, Vietnam Military Medical University, Hanoi, Vietnam.
Insights
CYP2C19 poor metabolizer phenotypes increase clopidogrel resistance and major adverse cardiovascular events (MACEs) risk in Vietnamese patients undergoing percutaneous coronary intervention (PCI). Genotyping can optimize antiplatelet therapy and improve patient outcomes.
Area of Science:
- Pharmacogenomics
- Cardiovascular Medicine
- Clinical Chemistry
Background:
- Acute coronary syndrome (ACS) is a significant cause of mortality.
- Clopidogrel resistance (CR) presents a challenge in ACS treatment.
- CYP2C19 genetic variations influence clopidogrel efficacy.
Purpose of the Study:
- To investigate the impact of CYP2C19 genetic variants on CR.
- To assess the association between CYP2C19 variants and major adverse cardiovascular events (MACEs).
- To evaluate these associations in Vietnamese patients undergoing percutaneous coronary intervention (PCI).
Main Methods:
- Descriptive cross-sectional study with prospective longitudinal follow-up (n=113).
- Amplification Refractory Mutation System (ARMS)-PCR used for CYP2C19 genotyping and phenotyping.
- Clopidogrel resistance defined as platelet aggregation ≥ 46%; MACEs recorded within 30 days post-PCI.
Main Results:
- Clopidogrel resistance (CR) rate was 29.9%; MACEs incidence was 15.9%.
- Higher frequencies of CYP2C19*2, CYP2C19*3 polymorphisms, and poor metabolizer (PM) CYP2C19 phenotype observed in CR and MACE groups.
- PM CYP2C19 phenotype significantly predicted 30-day MACEs in ACS patients undergoing PCI (p < 0.001).
Conclusions:
- CYP2C19 PM phenotypes are strongly associated with increased CR and 30-day MACEs risk in Vietnamese ACS patients undergoing PCI.
- CYP2C19 genotyping is clinically significant for optimizing antiplatelet therapy.
- Personalized antiplatelet strategies based on CYP2C19 genotype can improve cardiovascular outcomes.
Introduction:
Acute coronary syndrome (ACS) is a leading cause of death, and clopidogrel resistance remains a major challenge in its treatment. This study aims to determine the impact of CYP2C19 genetic variants on clopidogrel resistance (CR) and major adverse cardiovascular events (MACEs) in Vietnamese patients undergoing percutaneous coronary intervention (PCI).
Methods:
We carried out a descriptive cross-sectional study, supplemented by a prospective longitudinal follow-up, on 113 ACS patients undergoing PCI with drug-eluting stent implantation at the Department of Cardiology, Military Hospital 103, from January 2015 to May 2018. We excluded patients with a decreased platelet count (< 100 × 10^9/L), a decreased estimated glomerular filtration rate (< 15 mL/min), ongoing bleeding, coagulation disorders, planned or recent surgery, or a coexisting malignancy. CR was defined as platelet aggregation ≥ 46%. The Amplification Refractory Mutation System (ARMS)-PCR was used to determine the CYP2C19 genotype and phenotype. Causes leading to patient readmission, such as angina, recurrent acute myocardial infarction, stroke, or death within 30 days, were recorded as MACEs.
Results:
The rate of CR was 29.9% (33/113 patients), and the incidence of MACEs was 15.9% (18/113 patients). The frequencies of CYP2C192 and CYP2C193 polymorphisms, as well as the PM CYP2C19 phenotype, were higher in the CR and MACE groups compared to those without these characteristics (p = 0.24, 0.006, and < 0.001, respectively). The PM CYP2C19 phenotype was predictive of 30-day MACEs in ACS patients undergoing PCI with stent implantation (p < 0.001).
Discussion:
Our findings demonstrate a strong association between CYP2C19 PM phenotypes and increased risks of both clopidogrel resistance and 30-day MACEs in Vietnamese ACS patients undergoing PCI. These results underscore the clinical significance of CYP2C19 genotyping in optimizing antiplatelet therapy and enhancing outcomes in this patient population.
Conclusion:
PM CYP2C19 phenotypes were associated with an increased risk of CR and MACEs in Vietnamese patients undergoing PCI with stent implantation.
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