Tongxinluo, a traditional Chinese medicine made from extracts of multiple plants and insects, significantly reduced myocardial infarction (MI), stroke, and related events when used alongside guideline-directed treatments in patients with ST-segment elevation myocardial infarction (STEMI), results of a large trial suggest.
The double-blind China Tongxinluo Study for Myocardial Protection in Patients With Acute Myocardial Infarction (CTS-AMI) included 3777 adult patients, mean age 61 years, 76.9% men, with STEMI at 124 centers in China.
Researchers randomly assigned patients to receive oral Tongxinluo using a loading dose of eight capsules (2.08 g) followed by a maintenance dose of four capsules (1.04 g) or oral placebo three times a day for 12 months.
Doctors were instructed to also provide STEMI guideline-directed treatments, which include dual antiplatelet therapy and coronary reperfusion (percutaneous coronary intervention or thrombolysis).
The primary endpoint was major adverse cardiac and cerebrovascular events (MACCEs) at 30 days, a composite of cardiac death, myocardial reinfarction, emergent coronary revascularization, and stroke.
At 30 days, 3.4% in the Tongxinluo group and 5.2% in the placebo group had a MACCE (relative risk [RR], 0.64; 95% CI, 0.47-0.88; risk difference [RD], -1.8%; 95% CI, -3.2% to -0.6%; P = .006).
Individual components of MACCEs were also significantly lower in the Tongxinluo group, including 30-day cardiac death (3.0% vs 4.2%; RR, 0.70; 95% CI, 0.50-0.99; P = .04) and myocardial reinfarction (0% vs 0.5%; RR, 0.35; 95% CI, 0.13-0.99; P = .003), but there was no significant difference in 30-day stroke rate.
At 1 year, the Tongxinluo group had a lower MACCE rate than did the placebo group (5.3% vs 8.3%; hazard ratio [HR], 0.64; 95% CI, 0.49-0.82; P = .001), an almost significant lower rate of all-cause death (5.1% vs 6.6%; HR, 0.77; 95% CI, 0.59-1.01; P = .06), and lower rates of other outcomes.
Rates of nonfatal serious adverse events were similar (2.2% in the Tongxinluo and 2.8% in the placebo groups; P = .25), but the Tongxinluo group had more adverse drug reactions (2.1% vs 1.1%; P = .02), which were mainly driven by symptoms in the digestive system such as stomach discomfort and nausea.
Unlike most traditional Chinese medicine research, the design of this study incorporated all key elements of randomized clinical trials, including placebo control and blinding in addition to randomization, so it “may serve as a model for future clinical trials to evaluate the safety and efficacy of traditional Chinese medicine,” the authors conclude.
In an accompanying editorial, Richard G. Bach, MD, Cardiovascular Division, Washington University School of Medicine in St Louis, Missouri, expressed skepticism about whether the benefits of Tongxinluo can be extrapolated to populations outside China that have distinct genetic backgrounds, lipid profiles, and diets. He also stressed that the active ingredients and mechanisms of action of Tongxinluo are unknown and noted reports suggesting that traditional Chinese medicines can contain undeclared material, heavy metals, and other adulterants associated with potentially toxic effects.
In an Editor’s Note, Gregory Curfman, MD, said in making a judgment about the validity of this research, “the editors were faced with the task of walking a fine line between skepticism and plausibility.” Though all patients should receive beta-blockers and an angiotensin-converting enzyme (ACE) inhibitor or angiotensin II receptor blocker (ARB) after STEMI, use of these drugs was suboptimal in these patients. Still, benefits of Chinese medicine are plausible, said Curfman, noting research on the malaria drug artemisinin, which was isolated from a traditional Chinese medicine, was awarded the Nobel Prize.
The research was led by Yuejin Yang, MD, PhD, Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, and colleagues. It was published online on October 24, 2023 in JAMA. The results were previously reported at the American Heart Association Scientific Sessions 2022.
Despite the demonstrated clinical benefit of Tongxinluo, its active ingredients and the exact mechanisms of action have not been established. Use of guideline-directed medical therapy was suboptimal, with only 64% of patients prescribed beta-blockers and 51%-52% prescribed an ACE inhibitor or ARB during hospitalization, which may have affected the magnitude of the benefit of Tongxinluo. As study patients were all Chinese, the generalizability to other populations, especially in countries with higher adherence to guideline-directed medical therapy, is unknown.
The study received funding from the National Key Research and Development Program of China and a research grant from Shijiazhuang Yiling Pharmaceutical Co Ltd. Yuejin Yang reported receiving grants from Shijiazhuang Yiling Pharmaceutical Co Ltd and the National Key Research and Development Program of China; in addition, he has a patent related to the mechanisms of Tongxinluo in alleviating rat myocardial reperfusion injury and a patent related to the mechanisms of Tongxinluo on enhancing the protective effects of exosomes derived from mesenchymal stem cells in rat acute myocardial infarction. See paper for disclosures of other authors.
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