Traditional Chinese Medicine Compound (Tongxinluo) and Clinical Outcomes of Patients With Acute Myocardial Infarction
Author:
Yang Yuejin1, Li Xiangdong1, Chen Guihao1, Xian Ying2, Zhang Haitao1, Wu Yuan1, Yang Yanmin3, Wu Jianhua4, Wang Chuntong5, He Shenghu6, Wang Zhong7, Wang Yixin8, Wang Zhifang9, Liu Hui10, Wang Xiping11, Zhang Minzhou12, Zhang Jun1, Li Jia1, An Tao1, Guan Hao1, Li Lin1, Shang Meixia13, Yao Chen13, Han Yaling14, Zhang Boli15, Gao Runlin1, Peterson Eric D.16, Yang Yuejin17, Wu Jianhua17, Wang Chuntong17, He Shenghu17, Wang Zhong17, Wang Yixin17, Jing Yongquan17, Liu Linqiang17, Zhang Xuxia17, Pei Hanjun17, Xue Yuzeng17, Zheng Guanzhong17, Wang Changyu17, Zhao Zhongming17, Zheng Yanjie17, Duan Baoliang17, Zhang Gaoxing17, Liu Hui17, Wang Zhifang17, Fan Zeyuan17, Cao Wenzhai17, Zhang Huanyi17, Qi Xiaoyong17, Wang Xiping17, Wu Guoqing17, Gao Feng17, Bie Zidong17, Yue Long17, Hong Heng17, Qian Jun17, Dai Bingguang17, Dou Weiguang17, Yue Liming17, Zhan Zhongqun17, Liu Man17, Gao Xiaohong17, Lian Yitian17, Zheng Yi17, Zhang Jiangwu17, Man Ronghai17, Dong Peng17, Wu Lianling17, Deng Junguo17, Guo Yong17, Zhang Minzhou17, Li Jia17, Wang Zheying17, Dai Peisheng17, Siri Guleng17, Xu Qiming17, Li Xinyang17, Li Keqing17, Han Shengli17, Wang Huaixin17, Li Xia17, Yang Ping17, Zhang Haowen17, Liu Yuesen17, Xin Bo17, Zhang Menglang17, Cao Zhiduo17, Zhang Meng17, Ma Gang17, Wang Lei17, Song Jun17, Li Weiguo17, Li Hongchun17, Shang Zhenglu17, Feng Ouhua17, Zhang Hongjun17, Gao Hongtao17, Bao Rongqi17, Wang Fengshun17, Shang Linqing17, Qin Lei17, Wang Jianping17, Ma Genshan17, Cui Jiayu17, Wang Shixi17, Cheng Fangzhou17, Zhang Shujiang17, Liu Xianshi17, Cha Chunxi17, Sun Min17, Han Wenbao17, Lu Hang17, Wang Haiying17, Zhu Hongguang17, Wang Wei17, Wang Zhili17, Guo Yufeng17, Zhang Haisheng17, Shao Zhong17, Cui Xirong17, Lu Changlin17, Lv Zhan17, Zhang Jiyin17, Cui Guangkai17, Zhang Hongwei17, Han Ying17, Liu Wenli17, Zhou Bingfeng17, Ge Hua17, Zhang Liqun17, Chen Taihong17, Niu Bingying17, Mu Baoxi17, Zhang Jiao17, Guan Huaimin17, Chun Yuhu17, Zhang Hua17, Li Fangjiang17, Yin Shufang17, Wang Xu17, Zou Xiao17, Song Junshuai17, Hong Lang17, Zheng Mingqi17, Jiang Bo17, Liu Shuying17, Zhu Rui17, Liu Wenbo17, Zhang Jie17, Wu Bin17, Wu Zonggui17, Fang Quan17, Yuan Zuyi17, Gao Chuanyu17, Jiang Hong17, Li Xinli17, Bu Peili17, Gao Wei17, Liu Hongxu17, Xian Ying17, Gao Runlin17, Zhang Boli17, Han Yaling17, Ge Junbo17, Peterson Eric17, Chen Shaoliang17, Pu Jielin17, Zheng Qingshan17, Huang Congxin17, Shen Weifeng17, Wu Yuan17, Yao Chen17, Yan Xiaoyan17, Shang Meixia17, Fan Xiaohan17, Cheng Huaibing17, Chang Wenlan17, Wang Hui17, Li Zhi17, Zhai Wenxuan17, Zhu Zhenghui17, Li Hui17, Wang Jianpeng17, Tao Jin17, Xu Bo17, Sun Meiying17, Wu Fan17, Zou Tongqiang17, Chang Yue17, Yin Peng17, Shen Junyan17, Zhang Yaxing17, Huang Yunfei17, Chen Guihao17, Li Xiangdong17, Xu Yi17, Yang Jingang17, Zhang Haitao17, Jin Chen17, Wang Min17,
Affiliation:
1. State Key Laboratory of Cardiovascular Disease, Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China 2. Departments of Neurology and Population and Data Science, University of Texas Southwestern Medical Center, Dallas 3. Emergency Center, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China 4. Department of Cardiology, Xiuyan Manchu Autonomous County Central People’s Hospital, Anshan, Liaoning, China 5. Department of Cardiology, Xihua County People’s Hospital, Zhoukou, Henan, China 6. Department of Cardiology, Northern Jiangsu People’s Hospital, Yangzhou, Jiangsu, China 7. Department of Cardiology, The First Affiliated Hospital of the Medical College, Shihezi University, Shihezi, Xinjiang, China 8. Department of Cardiology, Xiajin People’s Hospital of Shandong Province, Xiajin, Shandong, China 9. Department of Cardiology, Xinxiang Central Hospital, Xinxiang, Henan, China 10. Department of Cardiology, Anyang District Hospital, Anyang, Henan, China 11. Department of Cardiology, Shihezi People’s Hospital, Shihezi, Xinjiang, China 12. Department of Cardiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China 13. Department of Biostatistics, Peking University Clinical Research Institute, Peking University First Hospital, Beijing, China 14. Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, Liaoning, China 15. State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China 16. Department of Medicine, University of Texas Southwestern Medical Center, Dallas 17. for the CTS-AMI Investigators
Abstract
ImportanceTongxinluo, a traditional Chinese medicine compound, has shown promise in in vitro, animal, and small human studies for myocardial infarction, but has not been rigorously evaluated in large randomized clinical trials.ObjectiveTo investigate whether Tongxinluo could improve clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI).Design, Setting, and ParticipantsRandomized, double-blind, placebo-controlled clinical trial was conducted among patients with STEMI within 24 hours of symptom onset from 124 hospitals in China. Patients were enrolled from May 2019 to December 2020; the last date of follow-up was December 15, 2021.InterventionsPatients were randomized 1:1 to receive either Tongxinluo or placebo orally for 12 months (a loading dose of 2.08 g after randomization, followed by the maintenance dose of 1.04 g, 3 times a day), in addition to STEMI guideline-directed treatments.Main Outcomes and MeasuresThe primary end point was 30-day major adverse cardiac and cerebrovascular events (MACCEs), a composite of cardiac death, myocardial reinfarction, emergent coronary revascularization, and stroke. Follow-up for MACCEs occurred every 3 months to 1 year.ResultsAmong 3797 patients who were randomized, 3777 (Tongxinluo: 1889 and placebo: 1888; mean age, 61 years; 76.9% male) were included in the primary analysis. Thirty-day MACCEs occurred in 64 patients (3.4%) in the Tongxinluo group vs 99 patients (5.2%) in the control group (relative risk [RR], 0.64 [95% CI, 0.47 to 0.88]; risk difference [RD], −1.8% [95% CI, −3.2% to −0.6%]). Individual components of 30-day MACCEs, including cardiac death (56 [3.0%] vs 80 [4.2%]; RR, 0.70 [95% CI, 0.50 to 0.99]; RD, −1.2% [95% CI, −2.5% to −0.1%]), were also significantly lower in the Tongxinluo group than the placebo group. By 1 year, the Tongxinluo group continued to have lower rates of MACCEs (100 [5.3%] vs 157 [8.3%]; HR, 0.64 [95% CI, 0.49 to 0.82]; RD, −3.0% [95% CI, −4.6% to −1.4%]) and cardiac death (85 [4.5%] vs 116 [6.1%]; HR, 0.73 [95% CI, 0.55 to 0.97]; RD, −1.6% [95% CI, −3.1% to −0.2%]). There were no significant differences in other secondary end points including 30-day stroke; major bleeding at 30 days and 1 year; 1-year all-cause mortality; and in-stent thrombosis (<24 hours; 1-30 days; 1-12 months). More adverse drug reactions occurred in the Tongxinluo group than the placebo group (40 [2.1%] vs 21 [1.1%]; P = .02), mainly driven by gastrointestinal symptoms.Conclusions and RelevanceIn patients with STEMI, the Chinese patent medicine Tongxinluo, as an adjunctive therapy in addition to STEMI guideline-directed treatments, significantly improved both 30-day and 1-year clinical outcomes. Further research is needed to determine the mechanism of action of Tongxinluo in STEMI.Trial RegistrationClinicalTrials.gov Identifier: NCT03792035
Publisher
American Medical Association (AMA)
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