Chinese herbal med cuts MACCE in STEMI, but questions remain

Tongxinluo, added to guideline-directed therapy, improves outcomes in patients with acute ST-segment elevation myocardial infarction (STEMI) in the large, multicentre CTS-AMI* study. But experts are clamouring for more evidence of efficacy.

Chinese patients treated with tongxinluo had lower rates of 30-day and 1-year major adverse cardiovascular and cerebrovascular events (MACCE) vs those given the placebo. The benefits were driven by fewer cardiac deaths. Severe STEMI complications were also lower with tongxinluo and did not result in major bleeding. [AHA 2022, abstract LBS-19508]

Tongxinluo is a traditional Chinese herbal medicine approved for angina and stroke in China. “Preclinical studies showed that the compound reduces myocardial no-reflow and infarct size following reperfusion and protects the cardiomyocytes,” reported CTS-AMI investigator Dr Yuejin Yang from the Fuwai Hospital, National Center for Cardiovascular Diseases, Beijing, China at AHA 2022.

He said the results are particularly important for STEMI patients in rural China where delays in timely reperfusion leave a substantial infarct size in many patients.

Herbs, centipede, and leech in a capsule: Whaaat?

Experts found as amazing the reduction in 30-day MACCE but were apprehensive about the active ingredients in tongxinluo. The medicine contains seven different herbs plus cockroach, scorpion, cicada, centipede, and leech.

“I also got stuck when I heard it got insects,” commented Dr Dipti Itchaporia from the Hoag Memorial Hospital Presbyterian, Newport Beach, California, US. “Yet, the magnitude of the effect seemed surprising. Listening in the audience was like, ‘wow, really?’ But I think we need to get more evidence that this works. So, I’m going to hold off my excitement until I know if we can reproduce the results in Europe or the US, or other populations.”

CTS-AMI population

The study enrolled 3,797 patients with STEMI or new left bundle-branch block at 124 hospitals across China. Patients were randomized to tongxinluo (n= 1,874) within 24 hours of symptom onset or placebo (n=1,881) with the same appearance, odour, and taste as tongxinluo, on top of guideline-directed therapy for 12 months.

Seventy-seven percent of the patients were male. Half of the overall population had hypertension, nearly half were smokers, and nearly one-quarter had hyperlipidaemia. Symptom-to-balloon time was nearly 6 hours in both arms for 93 –94 percent of patients who underwent primary percutaneous coronary intervention.

At 30 days, the rate of MACCE was 3.39 percent with tongxinluo vs 5.24 percent with placebo, for a relative risk reduction of 36 percent (RR, 0.64, 95 percent confidence interval [CI], 0.47–0.88).

Cardiac death at 30 days was 30 percent lower with tongxinluo vs placebo (2.97 percent vs 4.24 percent; RR, 0.70). There was no MI recurrence in the tongxinluo group vs nine in the placebo group (RR, 0.35). Strokes were numerically lower in the tongxinluo than in the placebo group (4 vs 9; RR, 0.44).  No patient had emergent coronary revascularization at 30 days.

At 1 year, rates of MACCE, cardiac death, repeat MI, and stroke were also significantly lower with tongxinluo. Rates of serious adverse events were similar at 2.17 percent and 2.75 percent with tongxinluo and placebo, respectively.

Renal injuries were fewer with tongxinluo (3.81 percent vs 5.30 percent), and there were no significant between-group differences in allergic rash, hepatic injury, prolonged activated partial thromboplastin time, or prothrombin time, digestive tract haemorrhage, nausea, diarrhoea, and headache or dizziness.

The benefit of tongxinluo was consistent across subgroups. “Our findings support the use of tongxinluo as an adjunct therapy in treating STEMI, at least in China and other developing countries,” said Yang.

Putting results into context

Study discussant  Kenneth Mahaffey from Stanford University, California, US, commented that although the 30-percent reduction in CV deaths stood out, it is important to reflect on the initial results.

“We haven’t seen a 30-percent reduction in CV death or overall mortality with any therapy in ages, despite a good background therapy,” he said. “So, we need to see how they ascertained all those events.”

More details about the analysis, trial conduct, and potential mechanisms will be informative, Mahaffey added. “These will include the result of intention-to-treat analyses, the methods used to ascertain and define the nonfatal endpoints, and any information about the use of evidence-based therapy such as anticoagulants, statins, beta-blockers, ACE inhibitors, and angiotensin receptor blockers.”