Pharmacogenetic testing in the management of patients with prosthetic heart valves

Abstract Background This study examined clinical, demographic, anthropometric, and inheritance factors that influence individual sensitivity to warfarin therapy after heart valve surgery. The clinical significance of the pharmacogenetic approach was assessed using the individual time frame and time spent in the INR therapeutic range. Purpose To study the influence of the preemptive panel-based pharmacogenetic testing on the effectiveness and safety of anticoagulant therapy in patients with prosthetic heart valves. Materials and methods The study included 928 patients (519 men and 409 female) (mean age 56±10 years) living in Western Siberia, Russia. Mainly there were patients with rheumatic heart disease, heart failure III NYHA and atrial fibrillation in 35% of cases. Mechanical heart valve prostheses were used in 70% of cardiac surgery cases. Real-time polymerase chain reaction was used for molecular genetic testing for polymorphisms VKORC, CYP2C9*2, CYP2C9*3, and CYP4F2. Results The frequencies of alleles and genotypes of CYP2C9 and VKORC1 in the study population of patients with heart valves prosthetic correspond to the distribution in Caucasian populations. Correlation between the calculated and actual therapeutic doses of warfarin was found according to the B.F Gage algorithm. In analyzing the dependence of the actual therapeutic dose of warfarin on polymorphic variants of the CYP2C9 and VKORC1 genes, it was shown that all the studied variants were associated with a therapeutic dose of warfarin, which was significantly different in carriers of different genotypes. Genotypes A/A CYP2C9*3 and G/G VKORC1 were associated with the largest deviations of the actual therapeutic dose from the calculated one. The clinical effectiveness of the pharmacogenetic approach was assessed according to the prevalence of the studied polymorphic variants of the CYP2C9 and VKORC1 genes in patients with prosthetic heart valves in the Kemerovo region. As a result, two groups of patients were formed using the “copy pair” method, without statistically significant differences in genetic, clinical, demographic, and anthropometric data. Usage of the pharmacogenetic testing at the beginning of warfarin therapy twice reduced time required to select a therapeutic dose of the anticoagulant, while the time within therapeutic INR range was increased by 20.2%. Conclusion The use of the panel-based pharmacogenetic approach at the beginning of warfarin therapy in patients with prosthetic he