Key result
CYP2C19*2 and CYP2C19*3 alleles linked to recurrent angina and reduced clopidogrel efficacy.
Why the study?
CYP2C19*2 and *3 variants affect clopidogrel metabolism and occur with different frequencies across ethnicities, potentially causing clopidogrel efficacy to differ among ethnic groups in Russia.
Does the presence of CYP2C19*2 or CYP2C19*3 alleles affect the clinical efficacy of clopidogrel in Russian and Buryat patients after coronary stenting for acute coronary syndrome?
Observational (n=292)
Does the presence of CYP2C19*2 or CYP2C19*3 alleles affect the clinical efficacy of clopidogrel in Russian and Buryat patients after coronary stenting for acute coronary syndrome?
p-value: p=0.015
The presence of CYP2C19 loss-of-function alleles (*2 and *3) is associated with reduced clopidogrel efficacy and recurrent angina in Russian and Buryat patients after coronary stenting, with the *3 allele being significantly more common in the Buryat population.
CYP2C19 genotyping may guide clopidogrel use in Russian and Buryat ACS patients; extends loss-of-function allele data to Buryat cohort but remains hypothesis-generating.
Background . Clopidogrel is often used in patients undergoing coronary stenting for acute coronary syndrome. However, the CYP2C19 variants rs4244285(*2), rs4986893 (*3) affect the metabolism of clopidogrel. These alleles occur with different frequencies in patients of different nationalities, so the clopidogrel efficacy may differ in ethnic groups living in Russia. Objective . to assess the associations between genetic determinants of the risk of thrombotic complications during clopidogrel treatment and the clinical characteristics of Buryat and Russian patients, in order to search for personalized informative prognosis markers. Design and methods . The study included 142 Buryat and 150 Russian patients undergoing coronary stent placement for acute coronary syndrome. All patients received clopidogrel. Patients were stratified by the presence of CYP2C19*2 , CYP2C19*3 alleles. In all patients efficacy endpoints were assessed, as well as corresponding therapy. Results . In Buryat patients CYP2C19*3 allele was significantly more common (11,6 % versus 1,3 %, p < 0,001) than in Russian. In Buryat patients, recurrence of anginal pain during exercise was associated with the CYP2C19*3 and/ or CYP2C19*2 genotypes (p = 0,015), as well as with the taking omeprazole (p = 0.015). In Russian patients, efficacy endpoints in clopidogrel treatment were associated with the presence of CYP2C19*2 and/or CYP2C19*3 alleles (p = 0.036). Conclusion . The presence of minor CYP2C19*3 and CYP2C19*2 alleles, along with the reports of recurrence of anginal pain during moderate and light exercise in Buryat patients may be considered as a prognostic sign of thrombotic complications.
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Zelenskaya et al. (2022) conducted an observational in Acute coronary syndrome (n=292). CYP2C19*2 and CYP2C19*3 alleles vs. Absence of CYP2C19*2 and CYP2C19*3 alleles was evaluated on Efficacy endpoints and recurrence of anginal pain during exercise (p=0.015). The presence of CYP2C19*2 and/or CYP2C19*3 alleles was associated with recurrence of anginal pain in Buryat patients (p=0.015) and efficacy endpoints in Russian patients (p=0.036).
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