CYP2C9 and VKORC1 variants and warfarin response in Kazakh patients following cardiac surgery

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.