The possibility of selecting optimal antiplatelet therapy in patients with coronary heart disease in terms of CYP2C19 polymorphism

Abstract

Aim. To estimate whether optimal antiplatelet therapy can be selected in terms of CYP2C19 polymorphism. Subjects and methods. The prospective randomized trial included 124 patients (93 men and 31 women) who were to undergo percutaneous coronary intervention. They initially received dual antiplatelet therapy: clopidogrel 75 mg + acetylsalicylic acid (ASA) 300 mg. Genetic testing was performed in all the patients to reveal the carriage of allelic variants of the genes of cytochrome P-450 isoenzymes and the efficiency of antiplatelet therapy was evaluated. The carriers of one allele (CYP2C19*2/*1) were randomized into 3 subgroups according to further antiplatelet therapy. The therapy was not changed in Subgroup 1. The dose of clopidogrel was increased up to 150 mg/day and that of ASA remained unchanged in Subgroup 2. In Subgroup 3, the therapy was completely changed to the regimen: ASA 300 mg + ticagrelor 90 mg twice daily. Three days later, platelet aggregation was reinvestigated in all the three subgroups. Results. In our investigation, the prevalence of carriage of at least one of the CYP2C19*2 alleles was about 35%. Comparison of the baseline platelet aggregation levels during the same platelet therapy showed statistically significant differences between the carriers and non-carriers: 32.7±11.6 and 44.8±12.9 (p=0.0024). Compared with the baseline values, there was a drug therapy switching-induced reduction in platelet aggregation in Subgroups 2 and 3 (p=0.0001 and p=0.0056, respectively). No statistically significant differences were found in Subgroup 1. Conclusion. The determination of CYP2C19 gene polymorphism allows a personalized approach to be applied in antiplatelet therapy for all patients with coronary artery disease.

Keywords

• genetic polymorphism
• clopidogrel
• thienopyridines
• platelets
• stenting