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Pharmacogenetics of warfarin dosing in Chinese adults with nonvalvular atrial fibrillation

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Abstract

Background

The guide for the use of genotype-guided warfarin dosing in patients for the treatment of non-valvular atrial fibrillation (AF) is still lacking.

Aim

We aimed to evaluate whether genotype-guided warfarin dosing is superior to conventional clinical dosing for the outcomes of interest in Chinese patients.

Method

Our study consisted of 508 newly recruited and 471 existing Chinese AF patients. Among the total 979 patients, 585 patients received their dose of warfarin determined by a genetic and clinical factor (gene group), while the remaining 394 patients whose dosing was determined empirically in control group. We incorporated CYP2C9 and VKORC1 genotypes into the gene group. The international normalized ratio (INR) measurement and standard protocols were used for further dose adjustment in both groups. The primary outcomes were the percentage of time in the therapeutic range (%TTR) and INR during 12-month follow-up. Secondary safety outcome included bleeding and thrombotic events.

Results

Compared with the control group, the average TTR of the gene group was higher [68.4 ± 20.6% vs 48.5 ± 21.6%, P < 0.001]. The average INR monitoring times to reach the therapeutic time in the gene group was lower (P < 0.001). The risk ratios (RR) for cumulative incidence of total bleeding events, minor bleeding events, gastrointestinal bleeding, and intracerebral bleeding events were not significantly different between the two groups (P > 0.05). Comparing to the analysis using existing 471 patients, the analysis using total 979 patients showed that the gene group experienced a lower (RR 0.4 (95% CI 0.2 to 0.8), P = 0.008) incidence of cumulative ischemic stroke.

Conclusion

Genotype-guided warfarin administration increases the average TTR, reaches higher TTR levels in the early anticoagulant phase, and significantly reduces the risk of ischemic stroke events.

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Availability of data and materials

The data and materials in the article are available from the corresponding author on reasonable request.

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Acknowledgements

We thank the editor and reviewers whose comments and suggestions helped improve and clarify this article.

Funding

Supported by the Yangzhou Science and Technology Bureau for Social Development (YZ2020074), Jiangsu Research Hospital Association for Precision Medication (JY202121), Yangzhou Thirteen Five Plan Special Funding for Strengthening Health through Science and Education (ZDRC20181), and China National Natural Science Foundation (81800250).

Author information

Authors and Affiliations

  1. Clinical Medical College, Yangzhou University, Nantong West Road No. 98, Yangzhou, 225001, Jiangsu, China

    Ye Zhu, Xiang Gu, Hua Zhu & Jia Liu

  2. Department of Cardiology, Northern Jiangsu People’s Hospital, Yangzhou, China

    Ye Zhu & Xiang Gu

  3. Department of Internal Medicine, Yangzhou Maternal and Child Health Care Hospital, Yangzhou, 225001, Jiangsu, China

    Jia You

  4. Department of Pharmacy, Northern Jiangsu People’s Hospital, Yangzhou, Jiangsu, China

    Hua Zhu & Jia Liu

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  1. Ye Zhu
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  2. Jia You
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  3. Xiang Gu
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  4. Hua Zhu
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Contributions

YZ was the patient’s doctor, reviewed the literature, and contributed to revision of the manuscript; JY, XG, and HZ collected the clinical data; JL designed and wrote the article.

Corresponding author

Correspondence to Jia Liu.

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The authors declare no competing interests.

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Impact statements

• The utility of genotype-guided dosing of warfarin can optimize individual warfarin dosing in Chinese AF patients.

• Genotype-guided warfarin administration increases the average TTR, reaches higher TTR levels in the early anticoagulant phase, and significantly reduces the risk of ischemic stroke events.

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Zhu, Y., You, J., Gu, X. et al. Pharmacogenetics of warfarin dosing in Chinese adults with nonvalvular atrial fibrillation. Eur J Clin Pharmacol 79, 427–435 (2023). https://doi.org/10.1007/s00228-023-03458-8

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  • DOI: https://doi.org/10.1007/s00228-023-03458-8

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