The role of CYP2C19 gene nucleotide sequence variants in assessing response to P2Y12 receptor inhibitor antiplatelet therapy in old patients with acute coronary syndrome

Aim. To assess the association between carrying CYP2C19 polymorphic variants and response to antiplatelet therapy, evaluated by residual platelet reactivity (Platelet Reactivity Units, PRU), in patients from different age groups.
Material and methods. The study included 140 patients with ACS receiving antiplatelet therapy with P2Y12 receptor inhibitors. The main group consisted of 70 patients aged 75 to 90 years (senile age), 35 taking clopidogrel, and 35 taking ticagrelor. The control group consisted of 70 patients aged 45 to 74 years (old and middle age), 35 taking clopidogrel, and 35 taking ticagrelor. The antiplatelet effect of therapy was assessed by studying non-stabilized whole blood using the VerifyNow point-ofcare assay. Carriage of the CYP2C19*2 and CYP2C19*3 alleles was determined using commercial reagent kits (Sintol LLC, Russia), and CYP2C19*17 was determined using commercial kits (Applied Biosystems, USA).
Results. The influence of CYP2C19 genetic variability on residual platelet aggregation was evaluated in elderly patients compared to patients of old and middle age. PRU values in the main group (senile age) (120.9 (48.5; 205.0)) on day 2 were statistically significantly higher (p=0.03) than in the control group (old and middle age) (96.06 (17.0; 174.5)). The same trend was observed in all subgroup comparison depending on the drug used: PRU values were statistically significantly higher in the main group of patients. Genotype distribution corresponded to the Hardy-Weinburg law for CYP2C19*17 and CYP2C19*2 except for CYP2C9*3. In control group patients receiving ticagrelor, carriage of the T allele (CYP2C19*17 locus) was statistically significantly associated with lower PRU levels (p=0.023). Furthermore, in the main study group among patients with PRU>208 receiving clopidogrel, carriers of the minor T allele at the CYP2C19*17 locus were statistically significantly more frequent (p=0.022) (CC genotype in 32% of patients, CT/TT genotypes in 80%).
Conclusion. Comparison of the main (senile age) and control (old and middle age) groups revealed that elderly age is associated with higher PRU values. A similar pattern was found when analyzing the main and control groups by subgroups depending on the drug taken: the proportion of patients with PRU values >208 was statistically significantly higher among patients from the main group (senile age). The obtained results regarding the carriage of the minor T allele at the CYP2C19*17 locus and PRU values in the main group could be associated with the phenomenon of phenoconversion, comorbidity, and polypharmacy in elderly patients.

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