In a recently published study, Dr clothesResearchers investigated whether Tongxinluo, a Chinese medicinal compound, could improve clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI).
STEMI is a major life-threatening condition worldwide. Despite reperfusion treatment and optimal medical management, patients with STEMI face an increased risk of cardiovascular disease recurrence and in-hospital mortality. Tongxinluo has shown promising potential in animals, in vitroand small-scale trials in myocardial infarction patients.
Studies have indicated that components such as paeoniflorin, ginsenoside RG1 and ginsenoside RB1 in tongxinluo have cardioprotective properties. Larger randomized controlled trials (RCTs) are needed to facilitate drug development and clinical translation.
About the study
In the current study, researchers evaluated the effect of Tongxinluo use by STEMI patients treated with STEMI guideline-directed medications such as coronary reperfusion and dual antiplatelet therapy.
Placebo-controlled, double-blind RCT [The China Tongxinluo Study for Myocardial Protection in Patients with Acute Myocardial Infarction (CTS-AMI)] Includes adults diagnosed with ST-segment elevation myocardial infarction within one day of symptom onset. Patients were recruited from 124 hospitals across China between 23 May 2019 and 8 December 2020 and followed until 15 December 2021. ST-segment elevation was ≥ 0.2 mV in participants leading to two adjacent or new left bundle-branch blocks.
Individuals were randomized 1:1 to receive oral tongxinluo or placebo drug 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 therapy.
The primary study endpoint was a composite measure of one-month major adverse cardiovascular or cerebrovascular events (MACCEs), 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 characteristics, laboratory investigations and electrocardiogram (ECG) were obtained during hospitalization. In addition, ECGs were performed at two hours, 24 hours, and several days after hospitalization/reperfusion. Exploratory analyzes were performed based on onset-to-arrival (≤12 hours, more than 12 hours) and serological creatinine levels during hospitalization (≤0.5 or above 0.5 of the normal range).
In addition, a per-protocol analysis was performed excluding major protocol deviations and those who failed to complete the 30-day follow-up assessment or failed to complete the predetermined minimum exposure to Tongxinluo (80% or higher adherence).
The cohort excluded subjects with severe STEMI complications, including mechanical complications, severe cardiogenic shock unresponsive to vasopressors, uncontrolled acute left-sided cardiac failure or pulmonary edema, and malignant arrhythmias uncontrollable with anti-arrhythmic agents.
Also, individuals with severe comorbidities, such as severe renal or hepatic dysfunction, severe infection, bleeding tendency, cancer, and life expectancy less than 12 months, were excluded from the analysis.
Of the 3,797 individuals, 3,777 (mean participant age 61 years, and 77% male) were considered for analysis, of whom 1,889 received tongxinluo and 1,888 received 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 MACCE was reported in 64 Tongxinluo (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 include cardiovascular mortality [56 (three percent) versus 80 (four percent); RR of 0.7, and RD of −1.2%]was significantly lower in tongxinluo recipients than in placebo recipients.
In one year, Tongxinluo recipients exhibited 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 changes in secondary endpoints such as stroke at one month, major bleeding at one and 12 months, all-cause mortality at 12 months, and stent coagulation (within 24 hours; one to 30 days; one month to one year). Adverse side effects were more common in tongxinluo recipients than in placebo recipients [40 (two percent) versus 21 (one percent)] and mainly include gastrointestinal symptoms such as nausea and abdominal discomfort.
Tongxinluo has also been shown to increase myocardial microvascular perfusion and protect endotheliocytes and cardiomyocytes from ischemic/reperfusion-induced mortality by reducing myocardial ischemic/reperfusion damage. Tongxinluo may stabilize and slow the evolution of coronary plaques by reducing intraplaque inflammation and neovascularization. Tongxinluo has also been shown in studies to stabilize arterial plaques, reduce serious cardiovascular events, and delay the onset of the first event.
Overall, the study results showed that in STEMI patients, Tongxinluo compound, as an adjunct to STEMI therapy, significantly improved one- and 12-month cardiovascular outcomes. However, further investigation is needed to elucidate the underlying biological mechanisms of Chinese medicine in STEMI.