Aspirin combined with clopidogrel has been widely used in the treatment of coronary heart disease with stent implantation. However, clopidogrel is a kind of precursor drug, which has many proteins involved in the process of absorption, metabolism, biological effect and drug clearance. Gene polymorphism encoding these proteins may affect the expression of corresponding proteins, thus affecting the antiplatelet effect of clopidogrel.
In Chinese population, it is not clear whether the gene polymorphism of many related proteins affects the risk of cardiovascular events in patients with coronary heart disease. In the recent acc.20/wcc conference, a team led by Professor Li Chunjian from the Department of cardiovascular medicine, the First Affiliated Hospital of Nanjing Medical University reported their research results in this field.
Introduction to experts
Professor Li Chunjian
Chief physician, Professor, doctoral supervisor, medical doctor
Visiting scholar of Heidelberg University in Germany and McMaster University in Canada; now deputy director of cardiovascular medicine administration and director of coronary care area of the First Affiliated Hospital of Nanjing Medical University (Jiangsu People's Hospital); training instructor of coronary intervention treatment of Health Care Commission
? Member of intervention cardiology group of cardiovascular branch of Chinese Medical Association; member of thrombus prevention and Control Professional Committee of cardiovascular branch of Chinese Medical Association; member of integrated cardiology Professional Committee of integrated medicine branch of Chinese Medical Association; member of Standing Committee of cardiovascular equipment technology professional committee of China Medical Equipment Association; prevention of China Medical Care International Exchange Promotion Association (CPAM) Member of the Standing Committee of the Youth Committee of the treatment branch; vice chairman of Jiangsu Province of CPAM heart disease branch; member of the cardiovascular physician branch of Jiangsu Physician Association; member of the collateral disease branch of Jiangsu traditional Chinese Medicine Association; chairman of Jiangsu ctoclub
research method
This prospective study included 1452 patients with coronary heart disease who received stent implantation, all of whom received one-year aspirin combined with clopidogrel dual antiplatelet therapy. After 5 days of clopidogrel administration, ADP induced platelet aggregation rate was measured by light turbidimetric method, and gene polymorphisms of 40 SNPs of 18 key proteins were detected Sex.
The researchers collected baseline data, treatment process, operation related data, drug treatment plan and other data, and conducted clinical follow-up.
The primary end point of the study was a major cardiovascular adverse event within 1 year after stent implantation, defined as a composite end point for cardiovascular death, nonfatal myocardial infarction, and ischemic stroke.
Research findings
During one-year follow-up, 44 patients had major cardiovascular adverse events. According to the analysis of 40 SNPs, only CYP2C19 * 2A allele carriers showed an increased risk of major cardiovascular adverse events compared with non-A allele carriers (adjusted risk ratio 2.05; 95% confidence interval, 1.01-4.19; P = 0.048) after adjusting for age, gender, myocardial infarction and left ventricular ejection fraction.
At the same time, CYP2C19 * 2A allele carriers also showed higher residual platelet aggregation rate than non carriers.
While CYP2C19 * 3, CYP2B6 rs3745274 and pear 1 rs12041331 gene polymorphisms were significantly related to the residual platelet aggregation function in the treatment period, but they were not found to be related to the risk of major cardiovascular adverse events within one year.
research conclusion
About 54.2% of Chinese patients with coronary heart disease (CHD) who received stent implantation had CYP2C19 * 2A allele, and the risk of major cardiovascular adverse events in CHD patients with CYP2C19 * 2A allele was about twice as high.
unscramble
The combination of aspirin and clopidogrel is a dual antiplatelet therapy widely used in patients with coronary heart disease after stent implantation. However, there is a large individual difference in the response of clopidogrel, which may be related to the gene variation related to the metabolism of clopidogrel. The increased rate of platelet aggregation after dual antiplatelet therapy may lead to a higher risk of ischemic events. How to identify high-risk patients and carry out individualized antiplatelet therapy is of great clinical significance.
The team led by Professor Li Chunjian from the cardiovascular department of the First Affiliated Hospital of Nanjing Medical University established a cohort of about 2500 patients. Through follow-up study, it was found that more than half of Chinese coronary heart disease patients carried CYP2C19 * 2A allele, while CYP2C19 * 2A allele carriers had higher risk of major cardiovascular adverse events. At the same time, these patients are more resistant to clopidogrel and need more intensive antiplatelet therapy. This study suggests that whether selective individualized therapy based on CYP2C19 * 2A gene can improve the prognosis of patients deserves further study.
The effect of CYP2C19 * 2 gene variation on the antiplatelet effect of clopidogrel has been widely concerned in clinical practice. On this study and its clinical significance, we conducted a more in-depth interview with Professor Li Chunjian.
Question: This study is aimed at the antiplatelet strategy after PCI. So, for patients who need long-term single drug antiplatelet therapy, how to choose drugs? Before using clopidogrel, should we pay attention to CYP2C19 * 2A allele? Please talk about your point of view.
Professor Li Chunjian: for patients with coronary heart disease who need long-term antiplatelet therapy with a single drug, we should pay more attention to the influence of gene polymorphism on the drug effect and carefully select the drug. This study shows that the carrier rate of CYP2C19 * 2A gene in Chinese population is 54.2%. After taking clopidogrel, the antiplatelet effect of this allele carrier is worse than that of non carrier, which will affect the secondary prevention effect of clopidogrel. The metabolic pathway and mechanism of aspirin were not affected by CYP2C19 gene polymorphism. Therefore, for patients who need single drug antiplatelet therapy, we suggest to give priority to aspirin with definite efficacy; for gene carriers with CYP2C19 * 2A deficiency, we should consider to use other ADP receptor antagonists instead of clopidogrel for dual platelet therapy.
Interactive Q & A: