Efficiency and safety of anticoagulant therapy in warfarin-treated patients — the influence of dietary vitamin K intake

Background. Warfarin has a wide variability in response, depending on the pharmacogenetic profile and vitamin K intake. The aim of the study was to analyze the amount of vitamin K supplied with food, its effect on the efficacy and safety of warfarin therapy in patients with different pharmacogenetic profiles. Materials and methods: The study included 34 people taking warfarin and 70 healthy volunteers, residents of St. Petersburg and the Leningrad region. Vitamin K consumption was determined using food diaries, genetic variants of VKORC1, CYP2C9 and CYP4F2 were determined using DNA-Technology kits on a DT-96 detection amplifier of the same manufacturer. Results. Vitamin K consumption by healthy volunteers was 84.4 ± 5.4 mcg/day, while in patients taking warfarin it was 63.9 ± 7.4 mcg/day (p < 0.0001), and the higher the daily vitamin K consumption by patients, the more stable the response and the shorter the time the patient spends outside the therapeutic INR range. The carriage of the AA3730 VKORC1 and TT1347 CYP4F2 genotypes, which determine a reduced ability to metabolize vitamin K, which entails a higher level of vitamin K in the liver and requires increased doses of warfarin, was 16 % and 7 % of patients, respectively. The *2 and *3 alleles of the CYP2C9 gene were detected in 33.8 % of patients. These alleles significantly affected the stability of warfarin therapy, so in 91 % of cases of exceeding the therapeutic interval of INR in patients, variants of CYP2C9*2 or CYP2C9*3 were detected, and only in 56 % of cases of INR below the therapeutic interval in patients were these variants detected (p < 0.03). Conclusion. Vitamin K consumption by patients taking warfarin is significantly lower than that of healthy residents of the North-West region. Low vitamin K consumption reduces the stability of hypocoagulation in patients taking warfarin.