Abstract
OBJECTIVES: To evaluate the association between CYP2C9 and VKORC1 polymorphisms and warfarin therapy outcomes in Kazakh patients following cardiac surgery, with a focus on dose requirements, INR stabilisation and bleeding complications. METHODS: A retrospective cohort study was conducted among 186 Kazakh patients (108 men and 78 women; mean age 59.2 ± 8.4 years) who underwent cardiac surgery and received warfarin therapy for at least 3 months. Clinical data and pharmacogenetic results were analysed from electronic medical records. The studied variants included CYP2C9 (2, 3) and VKORC1 (-1639G>A). Associations between genotype groups, warfarin dose requirements, INR control and adverse events were assessed. RESULTS: Patients with the CYP2C9 3/3 genotype required the lowest mean daily warfarin dose (1.9 ± 0.4 mg), whereas CYP2C9 1/1 carriers required the highest dose (4.8 ± 0.6 mg). Genotype-guided dosing was associated with faster INR stabilisation compared with conventional dosing (12.3 ± 3.9 vs. 20.5 ± 5.7 days) and a lower incidence of clinically significant bleeding events (6.2 vs. 14.8 %). CONCLUSIONS: The findings demonstrate that *CYP2C9* and *VKORC1* variants contribute to variability in warfarin response among Kazakh patients after cardiac surgery. Incorporating pharmacogenetic information into clinical decision-making may improve dose individualisation, anticoagulation control and treatment safety. Further prospective multicentre studies are required to confirm these findings.