Sublingual medication can protect brain cells in acute ischemic stroke, the latest achievement of Fan Dongsheng's team from Peking University Third Hospital

Previously, more than 1,000 neuroprotective drugs have been effective in rodent models, but all have failed in clinical translation. However, the drug introduced today not only has positive results, but is also cheap and easy to administer.

Stroke is a sudden interruption of cerebral blood flow, which often leads to severe physical disability and cognitive impairment. Among them, acute ischemic stroke (AIS) is the most common type of stroke, with high incidence, high prevalence, high recurrence rate, high disability rate and high mortality rate. It is one of the main causes of death and disability worldwide. At present, the treatment of acute ischemic stroke mainly focuses on vascular recanalization therapy, such as intravenous thrombolysis and intravascular mechanical thrombectomy. However, the effectiveness of these treatments is strictly limited by the time window, and not all patients can receive these treatments in time. Neuroprotection is another important means of treating acute ischemic stroke. Finding neuroprotective agents that can protect brain tissue and reduce damage has become an important direction of stroke research. Previous studies have confirmed that edaravone dextran injection can improve the neurological prognosis of patients with acute ischemic stroke, but at the same time it also has certain limitations, such as limited user population and inability to meet the full course of disease management. Therefore, drugs that are more convenient to administer and not restricted by medical scenarios are urgently needed in clinical practice. On February 19 this year, Professor Fan Dongsheng's team from the Department of Neurology at Peking University Third Hospital published an article titled "Sublingual EdaravoneDexborneol for the Treatment of Acute Ischemic Stroke: The TASTE-SL Randomized Clinical Trial" in the authoritative journal in the field of neurology, JAMA Neurology. Chief Physician Fu Yu from the Department of Neurology of the hospital was the first author, and other team members included experts from multiple research institutions such as Beijing Tiantan Hospital and Beijing Neuroscience Center. This study showed that sublingual edaravoneDexborneol tablets can significantly improve the neurological function outcomes of patients with acute ischemic stroke within 48 hours of onset on the 90th day.

Study Design and Results

This is a double-blind, placebo-controlled, multicenter, parallel-group, phase III randomized clinical trial conducted in 33 centers in China. A total of 914 patients aged 18 to 80 years, with a National Institutes of Health Stroke Scale (NIHSS) score between 6 and 20, a total motor deficit score of 2 or more in the upper and lower limbs, a clinical diagnosis of acute ischemic stroke, symptoms within 48 hours, and a modified Rankin Scale (mRS) score of ≤1 were enrolled, including 450 patients in the experimental group and 464 patients in the control group. Patients in the experimental group and the control group were treated with edaravone dexborneol sublingual tablets (edaravone 30 mg, dibonanil 6 mg) or placebo (edaravone 0 mg, dibonanil 60 μg), twice a day for 14 consecutive days, and followed up for 90 days. The primary efficacy outcome of the study was the proportion of patients with an mRS score of ≤1 on day 90. The results showed that 64.4% of patients in the trial group had an mRS score of ≤1 on day 90, which was significantly better than 54.7% in the control group, with an odds ratio of 1.50 (95% confidence interval, 1.15-1.95; P = 0.003). In terms of safety evaluation, the safety and tolerability of the sublingual tablets were good, and the incidence of common adverse reactions was similar to that of placebo, mostly related to the primary disease. The study confirmed that patients with acute ischemic stroke who were treated with edaravone and dextroborneol sublingual tablets for 14 days within 48 hours of symptom onset could sustainably improve neurological function.

****The study also has a number of limitations , including the failure to compare the effects of edaravone/dexamethasone sublingual tablets with intravenous administration, the exclusion of patients who received endovascular treatment, the inclusion of a large number of patients with mild strokes that resulted in nonsignificant secondary outcomes, the lack of quality of life assessments and bleeding event data, and the need to validate the findings in other ethnic groups.

Future research and application prospects

The discovery of edaravone dextrocarbamide sublingual tablets provides new hope for stroke patients. This drug can be administered sublingually and is rapidly absorbed, providing patients with a new treatment option. This result is encouraging and has important practical significance considering that edaravone dextrocarbamide sublingual tablets are low-cost, easy to administer (even in patients who are comatose, disabled or have difficulty swallowing), and easily available in China. It greatly expands the applicable population, especially those who cannot receive vascular recanalization treatment in time, and the convenient way of taking medicine can also improve patient medication compliance, help reduce stroke disability, and protect public health. The treatment of acute ischemic stroke has always been a challenge in the medical community. The low cost and easy administration of edaravone dextrocarbamide sublingual tablets make it particularly valuable in resource-limited settings. The findings of this study provide a new perspective for the treatment of acute ischemic stroke and emphasize the importance of continuous exploration and innovation in stroke treatment. Although the results of the study need further verification, this discovery has undoubtedly brought new vitality to the field of stroke treatment and may change the treatment strategy for stroke patients in the future. In the future, we look forward to seeing more research on edaravone and how it can play a role in stroke treatment around the world. At the same time, we also need to note that although this drug shows potential, it is not a panacea, and the best treatment for stroke patients still requires comprehensive consideration of individual conditions and multiple treatment options.

References

[1] Fu Y, Wang A, Tang R, Li S, Tian X, Xia X, Ren J, Yang S, Chen R, Zhu S, Feng X, Yao J, Wei Y, Dong X, Ling Y, Yi F, Deng Q, Guo C, Sui Y, Han S, Wen G, Li C, Dong A, Sun X, Wang Z, Shi Stroke: The TASTE-SL Randomized Clinical Trial. JAMA Neurol. 2024 Feb 19:e235716. doi: 10.1001/jamaneurol.2023.5716. Epub ahead of print. PMID: 38372981; PMCID: PMC10877503.

[2] Anderson CS, Song L. Promising Efforts to Define a Novel Approach to Neuroprotection for Acute Ischemic Stroke. JAMA Neurol. 2024 Feb 19. doi: 10.1001/jamaneurol.2023.5727. Epub ahead of print. PMID: 38372982.