Genotype-Guided Dosing of Warfarin in Chinese Adults: A Multicenter Randomized Clinical Trial.,Circulation: Genomic and Precision Medicine

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Genotype-Guided Dosing of Warfarin in Chinese Adults: A Multicenter Randomized Clinical Trial.
Circulation: Genomic and Precision Medicine ( IF 6.0 ) Pub Date : 2020-06-08 , DOI: 10.1161/circgen.119.002602
Chengxian Guo _{1,

2,

3} , Yun Kuang _{1,

3} , Honghao Zhou ₄ , Hong Yuan ₁ , Qi Pei ₂ , Jingle Li ₅ , Weihong Jiang ₅ , Chee M Ng ₆ , Xiaoping Chen _{4,

7} , Yong Huo ₈ , Yimin Cui _{9,

10} , Xiaobin Wang _{11,

12} , Jingjing Yu ₁ , Xue Sun ₁ , Wanying Yu ₁ , Peng Chen ₁ , Da Miao ₁ , Wenyu Liu ₁ , Zaixin Yu ₁₃ , Zewei Ouyang ₁₄ , Xiangjiang Shi ₁₄ , Chunmei Lv ₁₅ , Zijing Peng ₁₅ , Guozuo Xiong ₁₆ , Gaofeng Zeng ₁₇ , Jianping Zeng ₁₈ , Haiying Dai ₁₉ , Jianqiang Peng ₂₀ , Yuming Zhang ₁₃ , Fanghua Xu ₂₁ , Jie Wu ₂₂ , Xiaoliang Chen ₂₃ , Hao Gong ₂₄ , Zhiyuan Yang ₂₅ , Xianming Wu ₂₆ , Qiulian Fang ₂₇ , Liu Yang ₂₇ , Haigang Li ₂₈ , Hongyi Tan ₁ , Zhijun Huang ₁ , Xiaohong Tang ₅ , Qiong Yang ₅ , Shan Tu ₅ , Xiaoyan Wang ₅ , Yuxia Xiang ₁ , Jie Huang ₁ , Xiaomin Wang ₁ , Jingjing Cai ₅ , Shanjie Jiang ₅ , Lu Huang ₂ , Jinfu Peng ₂ , Liying Gong ₁ , Chan Zou ₁ , Guoping Yang _{1,

2,

3}

Affiliation

Center of Clinical Pharmacology, the Third Xiangya Hospital (C.G., Y.K., H.Y., J.Y., X. Sun, W.Y., P.C., D.M., W.L., H.T., Z.H., Y.X., J.H., Xiaomin Wang, L.G., C.Z., G.Y.), Central South University, Changsha, China.
Department of Pharmacy (C.G., Q.P., L.H., Jinfu Peng, G.Y.), Central South University, Changsha, China.
Research Center of Drug Clinical Evaluation (C.G., Y.K., G.Y.), Central South University, Changsha, China.
Department of Clinical Pharmacology, Xiangya Hospital (H.Z., Xiaoping Chen), Central South University, Changsha, China.
Department of Cardiology, The Third Xiangya Hospital (J.L., W.J., X.T., Q.Y., S.T., Xiaoyan Wang, J.C., S.J.), Central South University, Changsha, China.
College of Pharmacy, University of Kentucky, Lexington (C.M.N.).
Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics (Xiaoping Chen).
Department of Cardiology (Y.H.), Peking University Health Science Center, Beijing, China.
Department of Pharmacy, Peking University First Hospital (Y.C.), Peking University Health Science Center, Beijing, China.
Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences (Y.C.), Peking University Health Science Center, Beijing, China.
Department of Population, Family and Reproductive Health, Center on the Early Life Origins of Disease, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD (Xiaobin Wang).
Division of General Pediatrics and Adolescent Medicine, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD (Xiaobin Wang).
Department of Cardiology, Third Hospital of Changsha, China (Y.Z.).
Department of Cardiology, Shaoyang Central Hospital, China (Z.O., X. Shi).
Department of Cardiology, The First People's Hospital of Shaoyang, China (C.L., Z.P.).
Department of Vascular Surgery (G.X.), The Second Affiliated Hospital, University of South China, Hengyang.
Department of Cardiology (G.Z.), The Second Affiliated Hospital, University of South China, Hengyang.
Department of Cardiology, Xiangtan Central Hospital, China (J.Z.).
Department of Cardiology, Changsha Central Hospital, China (H.D.).
Department of Cardiology, Hunan Provincial People's Hospital, China (Jianqiang Peng).
Department of Cardiology, First People's Hospital of Xiangtan City, China (F.X.).
Department of Cardiology, First Affiliated Hospital of University of South China, Hengyang (J.W.).
Department of Cardiology, Chenzhou First People's Hospital, China (Xiaoliang Chen).
Department of Cardiology, The Fourth Hospital of Changsha, China (H.G.).
Department of Cardiology, Loudi Central Hospital, China (Z. Yang).
Department of Cardiology, Yiyang Central Hospital, China (X. Wu).
School of Mathematics and Statistics (Q.F., L.Y.), Central South University, Changsha, China.
Department of Pharmacy, Changsha Medical University, China (H.L.).

Background:Warfarin is an effective treatment for thromboembolic disease but has a narrow therapeutic index; optimal anticoagulation dosage can differ tremendously among individuals. We aimed to evaluate whether genotype-guided warfarin dosing is superior to routine clinical dosing for the outcomes of interest in Chinese patients.Methods:We conducted a multicenter, randomized, single-blind, parallel-controlled trial from September 2014 to April 2017 in 15 hospitals in China. Eligible patients were ≥18 years of age, with atrial fibrillation or deep vein thrombosis without previous treatment of warfarin or a bleeding disorder. Nine follow-up visits were performed during the 12-week study period. The primary outcome measure was the percentage of time in the therapeutic range of the international normalized ratio during the first 12 weeks after starting warfarin therapy.Results:A total of 660 participants were enrolled and randomly assigned to a genotype-guided dosing group or a control group under standard dosing. The genotype-guided dosing group had a significantly higher percentage of time in the therapeutic range than the control group (58.8% versus 53.2% [95% CI of group difference, 1.1–10.2]; P=0.01). The genotype-guided dosing group also achieved the target international normalized ratio sooner than the control group. In subgroup analyses, warfarin normal sensitivity group had an even higher percentage of time in the therapeutic range during the first 12 weeks compared with the control group (60.8% versus 48.9% [95% CI, 1.1–24.4]). The incidence of adverse events was low in both groups.Conclusions:The outcomes of genotype-guided warfarin dosing were superior to those of clinical standard dosing. These findings raise the prospect of precision warfarin treatment in China.Registration:URL: https://www.clinicaltrials.gov; Unique identifier: NCT02211326.

更新日期：2020-06-08

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