Traditional Chinese Medicine Compound (Tongxinluo) and Clinical Outcomes of Patients With Acute Myocardial Infarction : The CTS-AMI Randomized Clinical Trial
Importance: Tongxinluo, 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.
Objective: To investigate whether Tongxinluo could improve clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI).
Design, Setting, and Participants: Randomized, 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.
Interventions: Patients 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 Measures: The 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.
Results: Among 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 Relevance: In 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 Registration: ClinicalTrials.gov Identifier: NCT03792035.
| Errataetall: |
CommentIn: JAMA. 2023 Oct 24;330(16):1529-1530. - PMID 37874582 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:330 |
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| Enthalten in: |
JAMA - 330(2023), 16 vom: 24. Okt., Seite 1534-1545 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Yang, Yuejin [VerfasserIn] |
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| Links: |
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| Themen: |
Drugs, Chinese Herbal |
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| Anmerkungen: |
Date Completed 25.10.2023 Date Revised 25.04.2024 published: Print ClinicalTrials.gov: NCT03792035 CommentIn: JAMA. 2023 Oct 24;330(16):1529-1530. - PMID 37874582 Citation Status MEDLINE |
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| doi: |
10.1001/jama.2023.19524 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM363668535 |
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| 245 | 1 | 0 | |a Traditional Chinese Medicine Compound (Tongxinluo) and Clinical Outcomes of Patients With Acute Myocardial Infarction |b The CTS-AMI Randomized Clinical Trial |
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| 500 | |a Date Completed 25.10.2023 | ||
| 500 | |a Date Revised 25.04.2024 | ||
| 500 | |a published: Print | ||
| 500 | |a ClinicalTrials.gov: NCT03792035 | ||
| 500 | |a CommentIn: JAMA. 2023 Oct 24;330(16):1529-1530. - PMID 37874582 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Importance: Tongxinluo, 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 | ||
| 520 | |a Objective: To investigate whether Tongxinluo could improve clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI) | ||
| 520 | |a Design, Setting, and Participants: Randomized, 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 | ||
| 520 | |a Interventions: Patients 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 | ||
| 520 | |a Main Outcomes and Measures: The 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 | ||
| 520 | |a Results: Among 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 | ||
| 520 | |a Conclusions and Relevance: In 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 | ||
| 520 | |a Trial Registration: ClinicalTrials.gov Identifier: NCT03792035 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a tongxinluo |2 NLM | |
| 650 | 7 | |a Drugs, Chinese Herbal |2 NLM | |
| 700 | 1 | |a Li, Xiangdong |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Guihao |e verfasserin |4 aut | |
| 700 | 1 | |a Xian, Ying |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Haitao |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Yuan |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Yanmin |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Jianhua |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Chuntong |e verfasserin |4 aut | |
| 700 | 1 | |a He, Shenghu |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Zhong |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Yixin |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Zhifang |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Hui |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Xiping |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Minzhou |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Jun |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Jia |e verfasserin |4 aut | |
| 700 | 1 | |a An, Tao |e verfasserin |4 aut | |
| 700 | 1 | |a Guan, Hao |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Lin |e verfasserin |4 aut | |
| 700 | 1 | |a Shang, Meixia |e verfasserin |4 aut | |
| 700 | 1 | |a Yao, Chen |e verfasserin |4 aut | |
| 700 | 1 | |a Han, Yaling |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Boli |e verfasserin |4 aut | |
| 700 | 1 | |a Gao, Runlin |e verfasserin |4 aut | |
| 700 | 1 | |a Peterson, Eric D |e verfasserin |4 aut | |
| 700 | 0 | |a CTS-AMI Investigators |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Yuejin |e investigator |4 oth | |
| 700 | 1 | |a Wu, Jianhua |e investigator |4 oth | |
| 700 | 1 | |a Wang, Chuntong |e investigator |4 oth | |
| 700 | 1 | |a He, Shenghu |e investigator |4 oth | |
| 700 | 1 | |a Wang, Zhong |e investigator |4 oth | |
| 700 | 1 | |a Wang, Yixin |e investigator |4 oth | |
| 700 | 1 | |a Jing, Yongquan |e investigator |4 oth | |
| 700 | 1 | |a Liu, Linqiang |e investigator |4 oth | |
| 700 | 1 | |a Zhang, Xuxia |e investigator |4 oth | |
| 700 | 1 | |a Pei, Hanjun |e investigator |4 oth | |
| 700 | 1 | |a Xue, Yuzeng |e investigator |4 oth | |
| 700 | 1 | |a Zheng, Guanzhong |e investigator |4 oth | |
| 700 | 1 | |a Wang, Changyu |e investigator |4 oth | |
| 700 | 1 | |a Zhao, Zhongming |e investigator |4 oth | |
| 700 | 1 | |a Zheng, Yanjie |e investigator |4 oth | |
| 700 | 1 | |a Duan, Baoliang |e investigator |4 oth | |
| 700 | 1 | |a Zhang, Gaoxing |e investigator |4 oth | |
| 700 | 1 | |a Liu, Hui |e investigator |4 oth | |
| 700 | 1 | |a Wang, Zhifang |e investigator |4 oth | |
| 700 | 1 | |a Fan, Zeyuan |e investigator |4 oth | |
| 700 | 1 | |a Cao, Wenzhai |e investigator |4 oth | |
| 700 | 1 | |a Zhang, Huanyi |e investigator |4 oth | |
| 700 | 1 | |a Qi, Xiaoyong |e investigator |4 oth | |
| 700 | 1 | |a Wang, Xiping |e investigator |4 oth | |
| 700 | 1 | |a Wu, Guoqing |e investigator |4 oth | |
| 700 | 1 | |a Gao, Feng |e investigator |4 oth | |
| 700 | 1 | |a Bie, Zidong |e investigator |4 oth | |
| 700 | 1 | |a Yue, Long |e investigator |4 oth | |
| 700 | 1 | |a Hong, Heng |e investigator |4 oth | |
| 700 | 1 | |a Qian, Jun |e investigator |4 oth | |
| 700 | 1 | |a Dai, Bingguang |e investigator |4 oth | |
| 700 | 1 | |a Dou, Weiguang |e investigator |4 oth | |
| 700 | 1 | |a Yue, Liming |e investigator |4 oth | |
| 700 | 1 | |a Zhan, Zhongqun |e investigator |4 oth | |
| 700 | 1 | |a Liu, Man |e investigator |4 oth | |
| 700 | 1 | |a Gao, Xiaohong |e investigator |4 oth | |
| 700 | 1 | |a Lian, Yitian |e investigator |4 oth | |
| 700 | 1 | |a Zheng, Yi |e investigator |4 oth | |
| 700 | 1 | |a Zhang, Jiangwu |e investigator |4 oth | |
| 700 | 1 | |a Man, Ronghai |e investigator |4 oth | |
| 700 | 1 | |a Dong, Peng |e investigator |4 oth | |
| 700 | 1 | |a Wu, Lianling |e investigator |4 oth | |
| 700 | 1 | |a Deng, Junguo |e investigator |4 oth | |
| 700 | 1 | |a Guo, Yong |e investigator |4 oth | |
| 700 | 1 | |a Zhang, Minzhou |e investigator |4 oth | |
| 700 | 1 | |a Li, Jia |e investigator |4 oth | |
| 700 | 1 | |a Wang, Zheying |e investigator |4 oth | |
| 700 | 1 | |a Dai, Peisheng |e investigator |4 oth | |
| 700 | 1 | |a Siri, Guleng |e investigator |4 oth | |
| 700 | 1 | |a Xu, Qiming |e investigator |4 oth | |
| 700 | 1 | |a Li, Xinyang |e investigator |4 oth | |
| 700 | 1 | |a Li, Keqing |e investigator |4 oth | |
| 700 | 1 | |a Han, Shengli |e investigator |4 oth | |
| 700 | 1 | |a Wang, Huaixin |e investigator |4 oth | |
| 700 | 1 | |a Li, Xia |e investigator |4 oth | |
| 700 | 1 | |a Yang, Ping |e investigator |4 oth | |
| 700 | 1 | |a Zhang, Haowen |e investigator |4 oth | |
| 700 | 1 | |a Liu, Yuesen |e investigator |4 oth | |
| 700 | 1 | |a Xin, Bo |e investigator |4 oth | |
| 700 | 1 | |a Zhang, Menglang |e investigator |4 oth | |
| 700 | 1 | |a Cao, Zhiduo |e investigator |4 oth | |
| 700 | 1 | |a Zhang, Meng |e investigator |4 oth | |
| 700 | 1 | |a Ma, Gang |e investigator |4 oth | |
| 700 | 1 | |a Wang, Lei |e investigator |4 oth | |
| 700 | 1 | |a Song, Jun |e investigator |4 oth | |
| 700 | 1 | |a Li, Weiguo |e investigator |4 oth | |
| 700 | 1 | |a Li, Hongchun |e investigator |4 oth | |
| 700 | 1 | |a Shang, Zhenglu |e investigator |4 oth | |
| 700 | 1 | |a Feng, Ouhua |e investigator |4 oth | |
| 700 | 1 | |a Zhang, Hongjun |e investigator |4 oth | |
| 700 | 1 | |a Gao, Hongtao |e investigator |4 oth | |
| 700 | 1 | |a Bao, Rongqi |e investigator |4 oth | |
| 700 | 1 | |a Wang, Fengshun |e investigator |4 oth | |
| 700 | 1 | |a Shang, Linqing |e investigator |4 oth | |
| 700 | 1 | |a Qin, Lei |e investigator |4 oth | |
| 700 | 1 | |a Wang, Jianping |e investigator |4 oth | |
| 700 | 1 | |a Ma, Genshan |e investigator |4 oth | |
| 700 | 1 | |a Cui, Jiayu |e investigator |4 oth | |
| 700 | 1 | |a Wang, Shixi |e investigator |4 oth | |
| 700 | 1 | |a Cheng, Fangzhou |e investigator |4 oth | |
| 700 | 1 | |a Zhang, Shujiang |e investigator |4 oth | |
| 700 | 1 | |a Liu, Xianshi |e investigator |4 oth | |
| 700 | 1 | |a Cha, Chunxi |e investigator |4 oth | |
| 700 | 1 | |a Sun, Min |e investigator |4 oth | |
| 700 | 1 | |a Han, Wenbao |e investigator |4 oth | |
| 700 | 1 | |a Lu, Hang |e investigator |4 oth | |
| 700 | 1 | |a Wang, Haiying |e investigator |4 oth | |
| 700 | 1 | |a Zhu, Hongguang |e investigator |4 oth | |
| 700 | 1 | |a Wang, Wei |e investigator |4 oth | |
| 700 | 1 | |a Wang, Zhili |e investigator |4 oth | |
| 700 | 1 | |a Guo, Yufeng |e investigator |4 oth | |
| 700 | 1 | |a Zhang, Haisheng |e investigator |4 oth | |
| 700 | 1 | |a Shao, Zhong |e investigator |4 oth | |
| 700 | 1 | |a Cui, Xirong |e investigator |4 oth | |
| 700 | 1 | |a Lu, Changlin |e investigator |4 oth | |
| 700 | 1 | |a Lv, Zhan |e investigator |4 oth | |
| 700 | 1 | |a Zhang, Jiyin |e investigator |4 oth | |
| 700 | 1 | |a Cui, Guangkai |e investigator |4 oth | |
| 700 | 1 | |a Zhang, Hongwei |e investigator |4 oth | |
| 700 | 1 | |a Han, Ying |e investigator |4 oth | |
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