Clopidogrel is a representative drug that prevents blood clots and the recurrence of stroke. It must be converted into an active form in the body to be effective.

Still, the enzyme CYP2C19, which is involved in the activation process, varies in activity depending on the genotype. Several studies have revealed that some patients may experience significantly reduced efficacy.

A research team led by Professors Lee Kyung-yeol and Jung Yo-han of the Department of Neurology at Gangnam Severance Hospital announced on Wednesday that the effectiveness of antiplatelet agents may vary depending on a patient's genetic makeup. The study is drawing attention as it suggests the need for a gene-based personalized treatment strategy, moving beyond the era of “one-size-fits-all” medication in stroke treatment.

The research team analyzed the CYP2C19 gene type of 2,925 patients who visited the hospital within one week of stroke onset and tracked their clopidogrel-based treatment outcomes over a one-year period. Among the patients surveyed, 61.3 percent had a “loss-of-function allele (LOF allele).”

The presence of a LOF allele reduces CYP2C19 enzyme activity, leading to insufficient conversion of clopidogrel into its active form and thereby diminishing the drug's efficacy.

According to the research team's analysis, the incidence of cardiovascular events was 2.78 percent (49 out of 1,785 patients) in the group with loss-of-function alleles, which was approximately 57.5 percent higher than the 1.6 percent (18 out of 1,125 patients) in the group without the alleles. No significant differences were observed between the two groups in terms of major bleeding or overall mortality.

This suggests that while the efficacy of antiplatelet therapy varies depending on the genotype, the side effects are similar. Patients with a loss-of-function gene should consider alternative antiplatelet agents, as the preventive effect of clopidogrel is reduced in these individuals.

“We have confirmed the association between genetic type and drug response in stroke patients through clinical data,” Professor Lee said. “Stroke is a disease with a high risk of recurrence and for which preventive treatment is important, so we expect that drug selection based on individual genetic types will be reflected in clinical guidelines in the future.”

The study results were published in the latest issue of the international academic journal JAMA Network Open (IF 10.5) under the title “Cytochrome P450 2C19 Genotypes and Clopidogrel in Patients with Ischemic Stroke.”