Chinese herbal medicine may improve outcomes after STEMI
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CHICAGO — A drug derived from traditional Chinese medicine as an adjunct to guideline-directed therapy improved CV outcomes at 30 days and 1 year compared with placebo after revascularization, with no excess bleeding risk, a speaker reported.
“Despite reperfusion and optimal medical therapy, patients with STEMI still face a high risk of in-hospital mortality, myocardial no-flow and reperfusion injury, which have no targeted drugs, so far, worldwide,” Yuejin Yang, MD, PhD, FACC, FESC, professor in cardiology at Fuwai Hospital of Chinese Academy of Medical Sciences and Peking Union Medical College, National Center for Cardiovascular Diseases in Beijing, said during a presentation at the American Heart Association Scientific Sessions. “[There is] inadequate implementation of timely revascularization for STEMI [of 50% to 70%] in China and other developing countries, leaving substantial infarct size in many patients.”
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Traditional Chinese medicine compound
Yang said tongxinluo is a traditional Chinese medicine compound approved in China for angina and stroke in 1996 that has protective effects on the endothelium.
Prior studies have suggested that tongxinluo could reduce myocardial no-flow and infarct size via the protein kinase/nitric oxide synthase A pathway in acute MI and protect from reperfusion injury by inducing endothelial cell/cardiomyocyte crosstalk via small extracellular vesicles, according to the presentation.
CV and cerebrovascular outcomes
To test this hypothesis, Yang and colleagues conducted the China Tongxinluo Study for Myocardial Protection in Patients with Acute MI (CTS-AMI), for which they assigned tongxinluo or placebo as an adjunct to guideline-directed medical therapy (GDMT) within 24 hours of symptom onset in 3,777 adults hospitalized with STEMI, defined as ST segment elevation of more than 0.2 mV in more than two adjacent leads or new left bundle branch block (mean age, 61 years; 77% men).
At randomization, patients were given a loading dose of tongxinluo 2.08 g (eight capsules) or placebo. After revascularization, patients continued on tongxinluo 1.04 g (four capsules) three times per day plus GDMT for 12 months.
The primary endpoint was a composite of 30-day major adverse CV and cerebrovascular events, including cardiac death, myocardial reinfarction, emergent coronary revascularization and stroke.
In this study, the average symptom-to-needle time was nearly 4.5 hours.
At 30 days, researchers observed lower rates of major adverse CV and cerebrovascular events among patients assigned to tongxinluo compared with placebo (3.39% vs. 5.42%; RR = 0.64; 95% CI, 0.47-0.88; P = .006). This finding was primarily driven by fewer cardiac deaths in the tongxinluo group compared with placebo (2.97% vs. 4.24%; RR = 0.7; 95% CI, 0.5-0.99; P = .04) and moderately fewer myocardial reinfarctions (0% vs. 0.5%; RR = 0.35; 95% CI, 0.13-0.99; P = .003).
These findings remained significant out to 1 year after initial STEMI.
The researchers reported no significant between-group differences across various subgroup analyses.
Secondary outcomes, including 1-year rehospitalization for HF (P = .015), 24-hour reperfusion (P = .012) and renal injury, were also less frequent among patients assigned to tongxinluo compared with placebo. There was no increased risk for 30-day or 1-year major bleeding with tongxinluo compared with placebo, according to the study.
“Tongxinluo, a traditional Chinese medicine, significantly improved both 30-day and 1-year clinical outcomes in Chinese patients with STEMI, especially reducing cardiac death and severe complications,” Yang said during the presentation. “Tongxinluo did not result in severe side effects such as major bleedings. These findings support the use of tongxinluo as an adjunctive therapy in treating STEMI, at least in China and other developing countries.”
More data
After the presentation, Kenneth W. Mahaffey, MD, associate dean at the Stanford School of Medicine and director of Stanford Center for Clinical Research, discussed the need for more data on the potential mechanisms behind the effects of tongxinluo in STEMI.
“As we evaluate and reflect on these initial results, more details about the analysis, the trial conduct and the potential mechanisms will be informative,” Mahaffey said. “This will include the results by intention-to-treat analyses; the methods used to ascertain the nonfatal endpoints given their very small numbers; and then information about the use of evidence-based therapies. ... And then finally, data from the angiograms, the serial echos and biomarkers that were collected will provide potential elucidation of the mechanisms.
“As we await additional data, these results will likely support the use of this traditional Chinese medicine in STEMI patients in China. More studies are needed in other populations and treatment paradigms,” he said.
Perspective
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Martha Gulati, MD, MS, FACC, FAHA, FASPC
We rarely get good studies on supplements, or what some people call alternative medicines. This was a proper randomized controlled trial looking at a Chinese herbal medication, tongxinluo, compared with placebo in patients with acute MI, particularly STEMI.
This medication has been approved in China for 20 years. Mechanistically, we’re not sure exactly how it works. There have been multiple proposed mechanisms of why it would reduce the damage after acute MI, but it is used in China extensively.
What they were able to do in this randomized controlled trial is randomly assign patients to tongxinluo or placebo and found dramatic reduction in the primary endpoint of major adverse CV and cerebrovascular events, both within 30 days and out to 1 year. The reduction in the primary endpoint was driven by a 30% reduction in mortality.
The researchers were also able to assess safety compared with placebo, and there was no increased bleeding using tongxinluo. If anything, the placebo arm had more renal consequences than tongxinluo.
The questions that come to mind is, if this medication comes to the U.S., what else is in it, and whether it could adversely affect the heart. The problem is that, even supplements in our own country are not followed by a regulatory body, in the sense that we always know who’s prepared it, and that there may be other things in the medication. We will need more information.
Also, the time from symptom-onset-to-needle was longer than what we would want. In general, we talk about our door-to-balloon time, and I do not know if we have answers to whether that might have had an effect in this study. For the developing world, it’s not that easy. There’s not necessarily a unified ambulance service. If you’re in a rural part of these countries, just getting care can be a challenge. So the developing world will be looking at this trial with interest. Even in our world, we’ll be looking at this trial with interest because trials like CTS-AMI can be how some new medications get developed; some therapies that we use today have origins in supplements.
Barbra Streisand Women's Heart Center
Director of Preventive Cardiology
Smidt Heart Institute at Cedars-Sinai
President, American Society of Preventive Cardiology
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Yang Y, et al. LBS.03. High Impact Trials in Intervention and Surgery. Presented at: American Heart Association Scientific Sessions; Nov. 5-7, 2022; Chicago (hybrid meeting).
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