Genetic variants influenced the risk of bleeding and pharmacodynamics of rivaroxaban in patients with nonvalvular atrial fibrillation: A multicentre prospective cohort study

作者全名："Xiang, Qian; Wang, Zhe; Mu, Guangyan; Xie, Qiufen; Liu, Zhiyan; Zhou, Shuang; Zhang, Hanxu; Wang, Zining; Jiang, Jie; Hu, Kun; Zhang, Yatong; Zhao, Zinan; Yuan, Dongdong; Guo, Liping; Wu, Tingting; Zhang, Jinhua; Wang, Na; Xiang, Jing; Gu, Zhichun; Sun, Jianjun; Cui, Yimin"

作者地址："[Xiang, Qian; Wang, Zhe; Mu, Guangyan; Xie, Qiufen; Liu, Zhiyan; Zhou, Shuang; Wang, Zining; Hu, Kun; Cui, Yimin] Peking Univ First Hosp, Dept Pharm, Beijing, Peoples R China; [Wang, Zhe; Zhang, Hanxu; Cui, Yimin] Peking Univ, Sch Pharmaceut Sci, Hlth Sci Ctr, Beijing, Peoples R China; [Jiang, Jie] Peking Univ First Hosp, Dept Cardiol, Beijing, Peoples R China; [Zhang, Yatong; Zhao, Zinan] Beijing Hosp, Dept Pharm, Beijing, Peoples R China; [Yuan, Dongdong; Guo, Liping] Zhengzhou Seventh Peoples Hosp, Dept Pharm, Zhengzhou, Peoples R China; [Wu, Tingting; Zhang, Jinhua] Fujian Med Univ, Dept Pharm, Union Hosp, Fuzhou, Peoples R China; [Wang, Na; Xiang, Jing] Chongqing Med Univ, Dept Pharm, Affiliated Hosp 2, Chongqing, Peoples R China; [Gu, Zhichun] Shanghai Jiao Tong Univ, Ren Ji Hosp, Dept Pharm, Sch Med, Shanghai, Peoples R China; [Sun, Jianjun] Inner Mongolia Med Univ, Dept Pharm, Affiliated Hosp, Hohhot, Peoples R China; [Cui, Yimin] Peking Univ, Inst Clin Pharmacol, Beijing, Peoples R China; [Cui, Yimin] Peking Univ, Hlth Sci Ctr, Inst Clin Pharmacol, Sch Pharmaceut Sci, Beijing, Peoples R China"

通信作者："Cui, YM (通讯作者)，Peking Univ First Hosp, Dept Pharm, Beijing, Peoples R China.; Cui, YM (通讯作者)，Peking Univ, Hlth Sci Ctr, Inst Clin Pharmacol, Sch Pharmaceut Sci, Beijing, Peoples R China."

来源：CLINICAL AND TRANSLATIONAL MEDICINE

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:000989303500001

JCR分区：Q1

影响因子：7.9

年份：2023

卷号：13

期号：5

开始页：　

结束页：　

文献类型：Article

关键词：atrial fibrillation; bleeding; genetic polymorphism; pharmacodynamics; rivaroxaban

摘要："IntroductionIndividual variability of rivaroxaban was observed in clinical application. This study aimed to identify genetic variants associated with the variability of pharmacodynamics and bleeding risk of rivaroxbaban in patients with nonvalvular atrial fibrillation (NVAF). Materials and MethodsFrom June 2017, and July 2019, this study enrolled 257 patients with NVAF receiving rivaroxaban. Pharmacodynamics was assessed by determining anti-Factor Xa (anti-FXa) level 3 h after rivaroxaban administration as peak concentration. Whole-exome sequencing was performed to detected single nucleotide polymorphisms (SNPs). This study was registered (NCT03161496). ResultsThe bleeding events within 12 months were significantly related to the peak anti-FXa level (p = .027). SUSD3 rs76292544 was associated with 12-month bleeding events (odds ratio [OR]: 4.20, 95% confidence interval [CI]: 2.17-8.14, p = 6.43x10(-5)). Five SNPs including NCMAP rs4553122 (p = 2.29x10(-5)), PRF1 rs885821 (p = 7.02x10(-5)), PRKAG2 rs12703159 (p = 7.97x10(-5)), PRKAG2 rs13224758 (p = 8.70x10(-5)), and POU2F3 rs2298579 (p = 8.24x10(-5)) were associated with peak anti-FXa level. Genetic variants of 52 SNPs from 36 genes including GOT2 rs14221 and MMP13 rs640198 were potentially related to 12-month bleeding events caused by rivaroxaban's efficacy. ConclusionsPeak anti-FXa level was associated with risk of bleeding events in patients with NVAF receiving rivaroxaban. SUSD3 rs76292544 was suggestively associated with 12-month bleeding events and five SNPs (NCMAP rs4553122, PRF1 rs885821, PRKAG2 rs12703159, rs13224758 and POU2F3 rs2298579) were suggestively associated with peak anti-FXa level."

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