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Optimisation of warfarin-dosing algorithms for Han Chinese patients with CYP2C9*13 variants

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Abstract

Background

Existing pharmacogenetic algorithms cannot fully explain warfarin dose variability in all patients. CYP2C9*13 is an important allelic variant in the Han Chinese population. However, adjustment of warfarin dosing in CYP2C9*13 variant carriers remains unclear. To the best of our knowledge, this study is the first to assess the effects of adjusting warfarin dosages in Han Chinese patients harbouring CYP2C9*13 variants.

Methods

In total, 971 warfarin-treated Han Chinese patients with atrial fibrillation were enrolled in this study. Clinical data were collected, and CYP2C9*2, *3, *13 and VKORC1-1639 G > A variants were genotyped. We quantitatively analysed the effect of CYP2C9*13 on warfarin maintenance dose and provided multiplicative adjustments for CYP2C9*13 using validated pharmacogenetic algorithms.

Results

Approximately 0.6% of the Han Chinese population carried CYP2C9*13 variant, and the genotype frequency was between those of CYP2C9*2 and CYP2C9*3. The warfarin maintenance doses were significantly reduced in CYP2C9*13 carriers. When CYP2C9*13 variants were not considered, the pharmacogenetic algorithms overestimated warfarin maintenance doses by 1.03–1.16 mg/d on average. The actual warfarin dose in CYP2C9*13 variant carriers was approximately 40% lower than the algorithm-predicted dose. Adjusting the warfarin-dosing algorithm according to the CYP2C9*13 allele could reduce the dose prediction error.

Conclusion

Our study showed that the algorithm-predicted doses should be lowered for CYP2C9*13 carriers. Inclusion of the CYP2C9*13 variant in the warfarin-dosing algorithm tends to predict the warfarin maintenance dose more accurately and improves the efficacy and safety of warfarin administration in Han Chinese patients.

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Data availability

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

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Acknowledgements

We thank Elsevier Premium Language Editing Services for editing the English text of a draft of this manuscript.

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Author notes

  1. Dongxu Wang and Hualan Wu contributed equally to this work.

Authors and Affiliations

  1. Cardiovascular Department, Beijing Hospital, National Centre of Gerontology, Beijing, 100730, China

    Dongxu Wang, Hualan Wu, Qing Zhang, Xiaoyue Zhou, Yang An, Anxu Zhao, Jia Chong, Fang Wang, Jiefu Yang & Hao Chen

  2. Fuwai Hospital, Arrhythmia Center, Chinese Academy of Medical Sciences, National Center for Cardiovascular Diseases, 100037, Beijing, China

    Dongxu Wang

  3. Laboratory of Clinical Pharmacy, The Sixth Affiliated Hospital of Wenzhou Medical University, The People’s Hospital of Lishui, Lishui, 323020, China

    Shuanghu Wang

  4. The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Beijing Hospital, National Centre of Gerontology, Beijing, 100730, China

    Dapeng Dai

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  1. Dongxu Wang
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Contributions

DXW, DPD, and HC: study conception and design. DXW, HLW, QZ and XYZ: analysis and interpretation of data, drafting of the article, and statistical expertise. YA, AXZ, JC, SHW, FW, JFY, DPD, and HC: critical revision of the article for intellectual content and final approval of the article. DXW, HLW, QZ, AXZ and JC: provision of study materials or patients. HLW, QZ, XYZ, YA, AXZ, JC and SHW: administrative, technical, and logistic support. DXW, QZ, AXZ, and JC: collection of data. All authors contributed to the article and approved the submitted version.

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Correspondence to Hao Chen.

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Wang, D., Wu, H., Zhang, Q. et al. Optimisation of warfarin-dosing algorithms for Han Chinese patients with CYP2C9*13 variants. Eur J Clin Pharmacol 79, 1315–1320 (2023). https://doi.org/10.1007/s00228-023-03540-1

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