In a recent study published in JAMA, researchers investigated whether Tongxinluo, a Chinese medicinal compound, could improve clinical outcomes among ST-segment elevation myocardial infarction (STEMI) patients.
Study: Traditional Chinese Medicine Compound (Tongxinluo) and Clinical Outcomes of Patients With Acute Myocardial Infarction The CTS-AMI Randomized Clinical Trial. Image Credit: Image Point Fr/Shutterstock.com
Background
STEMI is a major life-threatening condition worldwide. Despite reperfusion treatment and optimal medical management, STEMI patients face increased risks of cardiovascular disease recurrences and in-hospital deaths. Tongxinluo has demonstrated promising potential in animal, in vitro, and small-scale trials among myocardial infarction patients.
Studies have indicated that ingredients such as peoniflorin, ginsenoside Rg1, and ginsenoside Rb1 in Tongxinluo have cardioprotective properties. Large randomized controlled trials (RCTs) are required to facilitate drug development and clinical translation.
About the study
In the present study, researchers evaluated the impact of Tongxinluo use by STEMI patients treated with STEMI guideline-directed medications such as coronary reperfusion and dual antiplatelet treatment.
The placebo-controlled, double-blinded RCT [The China Tongxinluo Study for Myocardial Protection in Patients with Acute Myocardial Infarction (CTS-AMI)] included adults diagnosed with ST-segment elevation myocardial infarction within a day of symptomatic onset. Patients were recruited from 124 hospitals across China between 23 May 2019 and 8 December 2020 and followed through 15 December 2021. ST-segment elevation ≥was 0.2 mV in more than two adjacent leads or new left bundle-branch blocks among the participants.
Individuals were randomized in a 1:1 ratio to receive Tongxinluo or a placebo drug orally for one year [loading dosage was 2.1 grams post-randomization (eight capsules), and maintenance dosage was 1.0 grams, thrice daily (four capsules)], in conjunction with STEMI therapies.
The primary study endpoint was one-month majorly adverse cardiovascular or cerebrovascular events (MACCEs), the composite measure of myocardial reinfarction, cardiac mortality, stroke, and emergent coronary artery revascularization. MACCE follow-ups were conducted every three to 12 months.
Baseline characteristics of participants, including clinical features, laboratory investigations, and electrocardiograms (ECGs), were obtained at hospitalization. In addition, ECG was performed at two hours, 24 hours, and several days post-hospitalization/reperfusion treatment. Exploratory analyses were performed based on onset-to-arrival (≤12 hours, more than 12 hours) and serological creatinine levels at hospitalization (≤0.5 or above 0.5 of the normal range).
In addition, a per-protocol analysis was performed, excluding individuals with major protocol deviations and those who failed to complete 30-day follow-up assessments or did not complete the predetermined minimal exposure to Tongxinluo (80% or higher adherence).
The team excluded individuals with severe STEMI complications, including mechanical complications, serious cardiogenic shock unresponsive to vasopressors, uncontrolled acute left-sided cardiac failure or pulmonary edema, and malignant arrhythmias that could not be controlled by anti-arrhythmic agents.
In addition, individuals with severe comorbidities, such as severe renal or hepatic dysfunction, severe infections, bleeding tendencies, cancers, and a life expectancy of below 12 months, were excluded from the analysis.
Results
Among 3,797 individuals, 3,777 (mean participant age of 61 years, and 77% men) were considered for the analysis, among whom 1,889 received Tongxinluo, and 1,888 received a placebo. The median duration of hospitalization was nine days. Most participants received statins, P2Y12 receptor inhibitors, and aspirin. Other therapies included β-blockers, angiotensin-converting enzyme (ACE) inhibitors, and angiotensin II receptor blockers (ARBs).
One-month MACCEs were reported among 64 Tongxinluo recipients (3.4%) versus 99 placebo recipients (5.2%) [relative risk (RR) of 0.6 and risk difference (RD) of −1.8%)]. In addition, individual MACCE components, including cardiovascular mortality [56 (three percent) versus 80 (four percent); RR of 0.7, and RD of −1.2%], were significantly lower among Tongxinluo recipients compared to the placebo recipients.
In one year, Tongxinluo recipients demonstrated lower MACCE rates [100 (five percent) versus 157 (eight percent); HR of 0.6, and RD of −3.0%] and cardiovascular mortality [85 (five percent) versus 116 (six percent); HR of 0.7, and RD of −1.6%].
The team observed non-significant alterations in secondary endpoints such as one-month stroke, major hemorrhage at one and 12 months, 12-month all-cause deaths, and coagulation in stents (within 24 hours; one to 30 days; one month to one year). Adverse side-effects were more frequent among Tongxinluo recipients than placebo recipients [40 (two percent) versus 21 (one percent)] and mainly included gastrointestinal symptoms such as nausea and stomach discomfort.
Tongxinluo has been demonstrated to increase myocardial microvascular perfusion while decreasing myocardial ischemic/reperfusion damage by protecting endotheliocytes and cardiomyocytes from ischemic/reperfusion-induced mortality. Tongxinluo may also stabilize and slow the evolution of coronary susceptible plaques by reducing intraplaque inflammation and neovascularization. Tongxinluo has been shown in studies to stabilize arterial plaques, minimize severe cardiovascular events, and postpone the commencement of the first event.
Conclusion
Overall, the study findings showed that among STEMI patients, the Tongxinluo compound, as an adjunct to STEMI therapies, significantly improved one- and 12-month cardiovascular outcomes. However, further investigations are required to elucidate the underlying biological mechanisms of Chinese medicine in STEMI.
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