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CYP2C9 and VKORC1 genotyping for the quality of long-standing warfarin treatment in Russian patients

Abstract

A total of 263 warfarin naive patients with indications to long-term anticoagulation were included in prospective multicenter study and randomized into Pharmacogenetics and Standard dosing groups. The loading warfarin dose in Pharmacogenetics group was calculated by Gage algorithm and corrected starting on day 5 of treatment according to INR. In Standard dosing group warfarin initial dose was 5 mg and starting on day 3 of treatment it was titrated according to INR. Pharmacogenetics dosing in comparison with prescription of starting dose of 5 mg decreased major bleedings (0 vs. 6, p = 0.031), time to target INR (11 [9–14] vs. 17 [15–24] days, p = 0.046), and frequency of INR fluctuations ≥4.0 (11% vs. 30.9%, p = 0.002). The advantages of the pharmacogenetics dosing were mainly achieved due to the patients with increased warfarin sensitivity.

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Acknowledgements

The authors appreciate the dedicated help of colleagues and nurses at the hospitals where this study was conducted and thank all participated patients. This study was partially supported by the Fund No. 8/3-280n-10 from the Moscow State Government and by funding from centers participated in this study.

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Correspondence to Elizaveta Panchenko.

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EP reports personal fees and nonfinancial support from Takeda, Pfizer, Boehringer Ingelheim, and Bayer during the conduct of the study; AD reports personal fees and nonfinancial support from Takeda, Instrumentation Laboratory, Diagnostica Stago during the conduct of the study; NV reports personal fees from Bayer, Pfizer, and Takeda, outside the submitted work during the conduct of the study; LG reports personal fees and nonfinancial support from Takeda, personal fees and nonfinancial support from Bayer, personal fees from Pfizer, during the conduct of the study; DZ reports personal fees and nonfinancial support from Takeda, AstraZeneca, Boehringer Ingelheim, and Bayer during the conduct of the study; IZ reports personal fees from Takeda, Pfizer, Boehringer Ingelheim, and Bayer during the conduct of the study; TV reports personal fees and nonfinancial support from Takeda, Pfizer, Boehringer Ingelheim, personal fees and Bayer during the conduct of the study; EK has nothing to disclose; ET has nothing to disclose; OZ has nothing to disclose; DT and IG are employees of DNA-Technology JSC, Moscow; GL has nothing to disclose; SS has nothing to disclose; NV has nothing to disclose; OS has nothing to disclose; AG has nothing to disclose.

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Panchenko, E., Kropacheva, E., Dobrovolsky, A. et al. CYP2C9 and VKORC1 genotyping for the quality of long-standing warfarin treatment in Russian patients. Pharmacogenomics J 20, 687–694 (2020). https://doi.org/10.1038/s41397-020-0157-2

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