Traditional Chinese Medicine Compound (Tongxinluo) and Clinical Outcomes of Patients With Acute Myocardial Infarction
Authors: Yang Yuejin , Li Xiangdong , Chen Guihao , Xian Ying , Zhang Haitao , Wu Yuan , Yang Yanmin , Wu Jianhua , Wang Chuntong , He Shenghu , Wang Zhong , Wang Yixin , Wang Zhifang , Liu Hui , Wang Xiping , Zhang Minzhou , Zhang Jun , Li Jia , An Tao , Guan Hao , Li Lin , Shang Meixia , Yao Chen , Han Yaling , Zhang Boli , Gao Runlin , Peterson Eric D. ,   CTS-AMI Investigators, Yang Yuejin , Wu Jianhua , Wang Chuntong , He Shenghu , Wang Zhong , Wang Yixin , Jing Yongquan , Liu Linqiang , Zhang Xuxia , Pei Hanjun , Xue Yuzeng , Zheng Guanzhong , Wang Changyu , Zhao Zhongming , Zheng Yanjie , Duan Baoliang , Zhang Gaoxing , Liu Hui , Wang Zhifang , Fan Zeyuan , Cao Wenzhai , Zhang Huanyi , Qi Xiaoyong , Wang Xiping , Wu Guoqing , Gao Feng , Bie Zidong , Yue Long , Hong Heng , Qian Jun , Dai Bingguang , Dou Weiguang , Yue Liming , Zhan Zhongqun , Liu Man , Gao Xiaohong , Lian Yitian , Zheng Yi , Zhang Jiangwu , Man Ronghai , Dong Peng , Wu Lianling , Deng Junguo , Guo Yong , Zhang Minzhou , Li Jia , Wang Zheying , Dai Peisheng , Siri Guleng , Xu Qiming , Li Xinyang , Li Keqing , Han Shengli , Wang Huaixin , Li Xia , Yang Ping , Zhang Haowen , Liu Yuesen , Xin Bo , Zhang Menglang , Cao Zhiduo , Zhang Meng , Ma Gang , Wang Lei , Song Jun , Li Weiguo , Li Hongchun , Shang Zhenglu , Feng Ouhua , Zhang Hongjun , Gao Hongtao , Bao Rongqi , Wang Fengshun , Shang Linqing , Qin Lei , Wang Jianping , Ma Genshan , Cui Jiayu , Wang Shixi , Cheng Fangzhou , Zhang Shujiang , Liu Xianshi , Cha Chunxi , Sun Min , Han Wenbao , Lu Hang , Wang Haiying , Zhu Hongguang , Wang Wei , Wang Zhili , Guo Yufeng , Zhang Haisheng , Shao Zhong , Cui Xirong , Lu Changlin , Lv Zhan , Zhang Jiyin , Cui Guangkai , Zhang Hongwei , Han Ying , Liu Wenli , Zhou Bingfeng , Ge Hua , Zhang Liqun , Chen Taihong , Niu Bingying , Mu Baoxi , Zhang Jiao , Guan Huaimin , Chun Yuhu , Zhang Hua , Li Fangjiang , Yin Shufang , Wang Xu , Zou Xiao , Song Junshuai , Hong Lang , Zheng Mingqi , Jiang Bo , Liu Shuying , Zhu Rui , Liu Wenbo , Zhang Jie , Wu Bin , Wu Zonggui , Fang Quan , Yuan Zuyi , Gao Chuanyu , Jiang Hong , Li Xinli , Bu Peili , Gao Wei , Liu Hongxu , Xian Ying , Gao Runlin , Zhang Boli , Han Yaling , Ge Junbo , Peterson Eric , Chen Shaoliang , Pu Jielin , Zheng Qingshan , Huang Congxin , Shen Weifeng , Wu Yuan , Yao Chen , Yan Xiaoyan , Shang Meixia , Fan Xiaohan , Cheng Huaibing , Chang Wenlan , Wang Hui , Li Zhi , Zhai Wenxuan , Zhu Zhenghui , Li Hui , Wang Jianpeng , Tao Jin , Xu Bo , Sun Meiying , Wu Fan , Zou Tongqiang , Chang Yue , Yin Peng , Shen Junyan , Zhang Yaxing , Huang Yunfei , Chen Guihao , Li Xiangdong , Xu Yi , Yang Jingang , Zhang Haitao , Jin Chen , Wang Min 
Published: October 2023

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 (&amp;lt;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