Clopidogrel is very effective, but be careful not to take it in vain

Author: Chen Tongyan, Deputy Chief Technician, Laboratory Diagnosis Center, Beijing Tiantan Hospital, Capital Medical University

Reviewer: Zheng Guanghui, Chief Technician, Laboratory Diagnosis Center, Beijing Tiantan Hospital, Capital Medical University

Cerebral infarction, also known as "cerebral thrombosis" by the common people, is a disease caused by blockage of blood vessels in the brain, leading to ischemia or hypoxia of brain tissue. Authoritative data show that in 2018 alone, 1,853 tertiary-level A hospitals in my country admitted 2,466,785 patients with cerebral infarction. In 2018, there were 13.7 million new cases of cerebral infarction worldwide, and 5.51 million new cases of cerebral infarction in China, accounting for nearly 1/3. Hypertension, hyperlipidemia, diabetes, vascular atherosclerosis, lack of exercise, irregular life and diet, etc. are all risk factors for cerebral infarction.

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1. Why is clopidogrel ineffective for some people?

Most patients with cerebral infarction will see their symptoms disappear or improve after clinical treatment. In order to prevent cerebral infarction from happening again, doctors will ask patients to take antiplatelet drugs for a long time, and clopidogrel is one of the first choice drugs. Although clopidogrel is effective, some patients with cerebral infarction will not see any effect no matter how long they take it. This may be due to genetics.

Clopidogrel is an inactive prodrug, which means it has no antiplatelet aggregation effect. After being absorbed by the small intestine, about 85% is hydrolyzed by esterase into inactive substances and excreted from the body with urine or feces. Only about 15% is converted into active products in the liver through the metabolic process mediated by the CYP2C19 enzyme, which is the substance that truly exerts its efficacy. These active products irreversibly bind to the adenosine diphosphate (ADP) receptor P2Y12 on the surface of platelets, inhibiting ADP-mediated platelet activation and aggregation and reducing the risk of thrombosis. In this way, the CYP2C19 enzyme is very important. Since the CYP2C19 gene encodes the CYP2C19 enzyme, and the CYP2C19 gene has polymorphism, the polymorphism affects the activity of the enzyme, which ultimately leads to different efficacy of clopidogrel in different patients even if they take the same dose.

Here we will briefly introduce the concept of gene polymorphism, which refers to the possibility that two or more different alleles may exist at a specific gene locus in the same biological population. Gene polymorphism is mainly controlled by genetics and is usually stable.

2. How do you know whether clopidogrel is effective?

In general, the different CYP2C19 genotypes of different patients lead to different activities of the CYP2C19 enzyme. The stronger the activity of the enzyme, the faster the metabolic process of clopidogrel mediated by it, and the stronger the drug effect. Therefore, according to the different CYP2C19 genotypes, patients with cerebral infarction can be divided into ultra-rapid metabolizers (UM), rapid metabolizers (EM), intermediate metabolizers (IM) and slow metabolizers (PM). Using different medication regimens for patients with different metabolic types can improve the therapeutic effect of the drug.

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It is particularly important to detect the CYP2C19 genotype of patients with cerebral infarction, which helps to guide the clinic on how to use clopidogrel correctly and effectively prevent patients with cerebral infarction from taking clopidogrel in vain. Therefore, before taking clopidogrel, it is recommended that patients with cerebral infarction test their CYP2C19 genotype to see what type of metabolism they have to avoid taking clopidogrel in vain. If you are a slow metabolizer or an intermediate metabolizer, then taking clopidogrel will basically not prevent thrombosis, and you should consider switching to other antiplatelet drugs.

References

[1]WANG YJ, LI ZX, GU HQ, et al. On behalf of China Stroke Statistics 2019 Writing Committee. Stroke Vasc Neurol, 2020, 5(3): 211-239.

[2] LEE CR, LUZUM JA, SANGKUHL K, et al. Clinical Pharmacogenetics Implementation Consortium guideline for CYP2C19 genotype and clopidogrel therapy: 2022 update. Clin Pharmacol Ther, 2022, 112(5): 959-967.