Jun 8th, 2020

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

Chengxian Guo, Yun Kuang, Honghao Zhou, Hong Yuan, Qi Pei, Jingle Li, Weihong Jiang, Chee M. Ng, Xiaoping Chen, Yong Huo, Yimin Cui, Xiaobin Wang, Jingjing Yu, Xue Sun, Wanying Yu, Peng Chen, Da Miao, Wenyu Liu, Zaixin Yu, Zewei Ouyang, Xiangjiang Shi, Chunmei Lv, Zijing Peng, Guozuo Xiong, Gaofeng Zeng, Jianping Zeng, Haiying Dai, Jianqiang Peng, Yuming Zhang, Fanghua Xu, Jie Wu, Xiaoliang Chen, Hao Gong, Zhiyuan Yang, Xianming Wu, Qiulian Fang, Liu Yang, Haigang Li, Hongyi Tan, Zhijun Huang, Xiaohong Tang, Qiong Yang, Shan Tu, Xiaoyan Wang, Yuxia Xiang, Jie Huang, Xiaomin Wang, Jingjing Cai, Shanjie Jiang, Lu Huang, Jinfu Peng, Liying Gong, Chan Zou, and Guoping Yang
Originally published 8 Jun 2020 | Circulation: Genomic and Precision Medicine
Genotype Guided Dosing 1179992727

Abstract

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 or older, 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 (%TTR) of the international normalized ratio (INR) 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 %TTR than the control group (58.8% vs. 53.2%, 95% confidence interval of group difference (95%CI): 1.1-10.2; P=0.01). The genotype-guided dosing group also achieved the target INR sooner than the control group. In subgroup analyses, warfarin normal sensitivity group had an even higher %TTR during the first 12 weeks compared to the control group (60.8% vs. 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.


Full text of this article is available at https://www.ahajournals.org/doi/10.1161/CIRCGEN.119.002602