Genotype-Guided Dosing of Warfarin in Chinese Adults A Multicenter Randomized Clinical Trial

被引：18

作者：

Guo, Chengxian ^{[1
,2
,4
]}

Kuang, Yun ^{[1
,4
]}

Zhou, Honghao ^{[1
,5
]}

Yuan, Hong ^{[1
]}

Pei, Qi ^{[2
]}

Li, Jingle ^{[3
]}

Jiang, Weihong ^{[3
]}

Ng, Chee M. ^{[9
]}

Chen, Xiaoping ^{[5
,6
]}

Huo, Yong ^{[10
]}

Cui, Yimin ^{[11
,12
]}

Wang, Xiaobin ^{[13
,14
]}

Yu, Jingjing ^{[1
]}

Sun, Xue ^{[1
]}

Yu, Wanying ^{[1
]}

Chen, Peng ^{[1
]}

Miao, Da ^{[1
]}

Liu, Wenyu ^{[1
]}

Yu, Zaixin ^{[7
]}

Ouyang, Zewei ^{[15
]}

Shi, Xiangjiang ^{[15
]}

Lv, Chunmei ^{[16
]}

Peng, Zijing ^{[16
]}

Xiong, Guozuo ^{[17
]}

Zeng, Gaofeng ^{[18
]}

Zeng, Jianping ^{[19
]}

Dai, Haiying ^{[20
]}

Peng, Jianqiang ^{[21
]}

Zhang, Yuming ^{[22
]}

Xu, Fanghua ^{[23
]}

Wu, Jie ^{[24
]}

Chen, Xiaoliang ^{[25
]}

Gong, Hao ^{[26
]}

Yang, Zhiyuan ^{[27
]}

Wu, Xianming ^{[28
]}

Fang, Qiulian ^{[8
]}

Yang, Liu ^{[8
]}

Li, Haigang ^{[29
]}

Tan, Hongyi ^{[1
]}

Huang, Zhijun ^{[1
]}

Tang, Xiaohong ^{[3
]}

Yang, Qiong ^{[3
]}

Tu, Shan ^{[3
]}

Wang, Xiaoyan ^{[3
]}

Xiang, Yuxia ^{[1
]}

Huang, Jie ^{[1
]}

Wang, Xiaomin ^{[1
]}

Cai, Jingjing ^{[3
]}

Jiang, Shanjie ^{[3
]}

Huang, Lu ^{[2
]}

机构：

[1] Cent South Univ, Ctr Clin Pharmacol, Third Xiangya Hosp, 138 TongZiPo Rd, Changsha 410013, Hunan, Peoples R China

[2] Cent South Univ, Dept Pharm, Changsha, Peoples R China

[3] Cent South Univ, Dept Cardiol, Third Xiangya Hosp, Changsha, Peoples R China

[4] Cent South Univ, Res Ctr Drug Clin Evaluat, Changsha, Peoples R China

[5] Cent South Univ, Dept Clin Pharmacol, Xiangya Hosp, Changsha, Peoples R China

[6] Cent South Univ, Inst Clin Pharmacol, Hunan Key Lab Pharmacogenet, Changsha, Peoples R China

[7] Cent South Univ, Dept Cardiol, Xiangya Hosp, Changsha, Peoples R China

[8] Cent South Univ, Sch Math & Stat, Changsha, Peoples R China

[9] Univ Kentucky, Coll Pharm, Lexington, KY 40506 USA

[10] Peking Univ First Hosp, Dept Cardiol, Beijing, Peoples R China

[11] Peking Univ First Hosp, Dept Pharm, Beijing, Peoples R China

[12] Peking Univ, Dept Pharm Adm & Clin Pharm, Sch Pharmaceut Sci, Hlth Sci Ctr, Beijing, Peoples R China

[13] Johns Hopkins Univ, Dept Populat Family & Reprod Hlth, Ctr Early Life Origins Dis, Bloomberg Sch Publ Hlth, Baltimore, MD USA

[14] Johns Hopkins Univ, Sch Med, Dept Pediat, Div Gen Pediat & Adolescent Med, Baltimore, MD 21205 USA

[15] Shaoyang Cent Hosp, Dept Cardiol, Shaoyang, Peoples R China

[16] First Peoples Hosp Shaoyang, Dept Cardiol, Shaoyang, Peoples R China

[17] Univ South China, Dept Vasc Surg, Affiliated Hosp 2, Hengyang, Peoples R China

[18] Univ South China, Dept Cardiol, Affiliated Hosp 2, Hengyang, Peoples R China

[19] Xiangtan Cent Hosp, Dept Cardiol, Xiangtan, Peoples R China

[20] Changsha Cent Hosp, Dept Cardiol, Changsha, Peoples R China

[21] Hunan Prov Peoples Hosp, Dept Cardiol, Changsha, Peoples R China

[22] Third Hosp Changsha, Dept Cardiol, Changsha, Peoples R China

[23] First Peoples Hosp Xiangtan City, Dept Cardiol, Xiangtan, Peoples R China

[24] Univ South China, Dept Cardiol, Affiliated Hosp 1, Hengyang, Peoples R China

[25] Chenzhou First Peoples Hosp, Dept Cardiol, Chenzhou, Peoples R China

[26] Fourth Hosp Changsha, Dept Cardiol, Changsha, Peoples R China

[27] Loudi Cent Hosp, Dept Cardiol, Loudi, Peoples R China

[28] Yiyang Cent Hosp, Dept Cardiol, Yiyang, Peoples R China

[29] Changsha Med Univ, Dept Pharm, Changsha, Peoples R China

来源：

CIRCULATION-GENOMIC AND PRECISION MEDICINE | 2020年 / 13卷 / 04期

关键词：

atrial fibrillation; control groups; pharmacogenetics; randomized controlled trial; warfarin; ATRIAL-FIBRILLATION; PHARMACOGENETICS; ALGORITHM; VKORC1; POLYMORPHISMS; STROKE;

D O I：

10.1161/CIRCGEN.119.002602

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 Z18 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.

引用

页数：10

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