Reference: JAMA. 2023 Oct 24;330(16):1534-1545
Practice Point: Tongxinluo may help patients with STEMIs in China, but isn’t likely to be on the formulary of your local hospital anytime soon.
EBM Pearl: A trial may have internal validity without external validity. In this case, we trust the results in the population studied but question the benefit in others.
Patients with acute ST-segment elevation myocardial infarction (STEMI) remain at high risk for in-hospital mortality and recurrent cardiovascular events, despite reperfusion therapy and other optimal medical management. Tongxinluo is a traditional Chinese medicine compound composed of extracts from plants and insects. It was approved in China for the treatment of angina pectoris and ischemic stroke in 1996. In 2019, an RCT (ENLEAT) of patients with acute STEMIs demonstrated significant improvements in perfusion but not clinical outcomes. More recently, a trial was conducted in China to investigate clinical outcomes in a large number of patients with acute STEMI treated with Tongxinluo.
The randomized trial included 3,797 adult patients with STEMIs presenting to the hospital within 24 hours after onset of symptoms. The patients were randomly assigned to guideline-directed therapy that included dual antiplatelet therapy and coronary reperfusion when needed PLUS either a treatment with Tongxinluo at a loading dose of 2.08 g followed by 1.04 g TID PO or placebo for 1 year. The primary outcome of the trial was the composite incidence of major adverse cardiac and cerebrovascular events (MACCEs) at 30 days, which included cardiac-specific death, myocardial reinfarction, emergent coronary revascularization, and stroke.
The intention-to-treat analysis included 99% of the patients (3,777 patients, mean age 61 years and 77% male) who took the allocated study drug. After 30 days, the incidence of MACCEs was significantly lower in the group treated with Tongxinluo (3.4% vs. 5.2%, p = 0.006), including lower risks of cardiovascular death (3% vs. 4.2%, p = 0.04) and myocardial reinfarction (0% vs. 0.5%, p = 0.003). A significantly lower incidence of MACCEs with Tongxinluo was also observed after 1 year. The patients in the Tongxinluo group had lower rates of severe complications of STEMI at 1 month and rehospitalization for heart failure at 1 year. There were no significant differences in major bleeding or in-stent thrombosis observed between the groups.
The authors of this large, double-blind trial conclude that Tongxinluo used as an adjunctive therapy to guideline-directed treatments reduces the risk of MACCEs, cardiac death, myocardial reinfarction, and severe STEMI complications. Based on the trial design and execution, we think the results are valid… in the population studied. However, only about 55% of participants got ACEs/ARBs, 64% got beta blockers and 75% got nitrates. Most got aspirin, statins, and P2Y12 inhibitors. In the US, all of these meds are given more consistently for the treatment of STEMIs, and we question whether the magnitude of benefit of Tongxinluo would be diminished in a population also receiving these medications. Safety and tolerability were also not fully assessed, which should really be evaluated before efficacy. We also wonder if this medicine could ever even be prescribed outside of China. It’s hard enough getting FDA approval for a single ingredient herbal remedy — the formulation listed in appendix 2 for Tongxinluo lists 12 ingredients! On the other hand, this study is a great example of using scientific methods to look at traditional remedies. This remedy, along with many traditional remedies, is available through the magic of the internet for about $8. It isn’t just a matter of whether you are willing to prescribe it: you may already have patients who are taking it.
For more information, see the topic ST-elevation Myocardial Infarction (STEMI) in DynaMed.
DynaMed EBM Focus Editorial Team
This EBM Focus was written by Dan Randall, MD, Deputy Editor at DynaMed, and Vincent Lemaitre, PhD, Medical Editor at DynaMed. Edited by Alan Ehrlich, MD, Executive Editor at DynaMed and Associate Professor in Family Medicine at the University of Massachusetts Medical School; Katharine DeGeorge, MD, MS, Senior Deputy Editor at DynaMed and Associate Professor of Family Medicine at the University of Virginia; Nicole Jensen, MD, Family Physician at WholeHealth Medical; Elham Razmpoosh, PhD, Postdoctoral fellow at McMaster University; and Sarah Hill, MSc, Medical Writer at DynaMed.