Traditional Chinese Medicine Compound (Tongxinluo) and Clinical Outcomes of Patients With Acute Myocardial Infarction

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

Traditional Chinese Medicine Compound and Clinical Outcomes in Acute Myocardial Infarction—Reply

“…In Reply In their letter to the editor, Drs Asham and Entezari-Maleki inquire about the TIMI and GRACE risk scores of patients enrolled in our recent study on Tongxinluo . The Table shows the similarity in the distribution of TIMI and GRACE scores at baseline, and the benefit of Tongxinluo in 30-day major adverse cardiac and cerebrovascular events across low-, intermediate-, and high-risk subgroups (all P values for interaction > .05).…”

“…In response to the letter by Dr Zakiev and colleagues about the stability of the effect of Tongxinluo, the ultra-performance liquid chromatography fingerprint for 10 different batches of Tongxinluo capsules was provided in eFigure 1 of Supplement 2 of the article . This eFigure showed the stability of the Tongxinluo capsule ingredients…”

Traditional Chinese Medicine Compound and Clinical Outcomes in Acute Myocardial Infarction

“…To the Editor A recent article reported a positive effect of a traditional Chinese drug (Tongxinluo) on outcomes of patients with acute myocardial infarction. Tongxinluo is a mixture of powders and extracts from multiple plant and insect products, so the concentration of active components may vary.…”

Traditional Chinese Medicine Compound and Clinical Outcomes in Acute Myocardial Infarction

“…To the Editor The China Tongxinluo Study for Myocardial Protection in Patients With Acute Myocardial Infarction (CTS-AMI) recently showed that the Chinese traditional medicine Tongxinluo significantly improved both 30-day and 1-year clinical outcomes of patients with acute ST-segment elevation myocardial infarction (STEMI). However, we are concerned that patient risk stratification was not included in this study.…”

“…Although the CTS-AMI study reported prognostic risk factors of mortality in STEMI, such as age, sex, diabetes, hypertension, and medications (aspirin, angiotensin-converting enzyme inhibitors, statins, and β-blockers), its omission of risk stratification may have affected the study results because these tools are necessary to choose the best STEMI treatment modalities based on the guidelines …”