UK Stroke Forum 2025 | Improving functional outcomes in AIS with neuroprotective agents: insights from clinical trials

Now, I will introduce another project that is a perspective on the recently published work that, as we all know, is also about the, regarding the neuroprotective therapy in the field of acute ischemic stroke patients who were treated with endovascular thrombectomy. And the clinical question is also that although the endovascular thrombectomy can achieve a high rate of recanalization, especially for patients with large vessel occlusion. But the functional outcomes of the patients who were treated with thrombectomy was not as good as we expected. And for example, the functional independence is less than 50% and the excellent outcome is only less than 30%. So how can we improve the, how can we further improve the prognosis of these part of patients who are treated with thrombectomy is a very important clinical question especially in the field of ischemic stroke and in this field a lot of review and project has been tackled on this question.

And in the FRONTIER trial, and we can see that a new neuroprotection agent has been used to test whether the NA1 can improve the functional outcome of this part of patients. As we all know that the NA1 is a very famous neuroprotectant agent in the field of acute ischemic stroke, and several clinical trials have been published, such as the ESCAPE-NA1. But unfortunately, the trial didn’t find that in patients who were treated with intravenous thrombectomy, NA1 can benefit these patients. And based on the clinical trial, the NA1-NEXT also tackled on patients who were not treated with intravenous thrombolysis, the subgroup of patients. But unfortunately, the ESCAPE-NEXT also didn’t find any beneficial effect of NA1. And based on the previous several previous clinical trials as a FRONTIER trial also launched to investigate whether the NA1 that was administered early in the patients who were suspected of large vessel occlusion, acute ischemic stroke. But in this trial, the result was also neutral and didn’t demonstrate that the functional benefits of NA1 in patients who were suspected of large vessel occlusion and treated with endovascular thrombectomy eventually. And we can see that there’s also some other neuroprotection therapy like NA1, but the NA1 has been regarded as the most promising neuroprotection agent in the field of acute ischemic stroke. But the several neutral results of the NA1 is also very surprising in this therapy field. And to some extent, it’s also disappointing. And I think that there are many questions we should do to further improve how can we use the neuroprotection to improve the functional outcome of patients who are treated with thrombectomy? And the first question is when we initiate the neuroprotection therapy, and the most promising therapy time points is maybe before the evaluation of the large infarction volume has been formation, has been developed. Because in the published clinical trials we found that even patients who are treated with neuroprotection and who are treated with thrombectomy, and lots of them has a large infarction score finally, and in this part of patients, maybe the large infarction score that has been developed that can cause a very severe deficits and even cause mortality.

And then the second question is which neuroprotection therapy or neuroprotective agents should we use. And now the NA1 has been demonstrated to be a neutral benefit in patients with stroke. And this drug has been considered as the most promising neuroprotection therapy. And in the future we should investigate other neuroprotection therapies, maybe the neuroprotection attack on multiple mechanisms of acute ischemic stroke injury maybe can play a better role than the agents that only target on one or two the signals or the targets of the injury. And also there’s the third question is in which phase of the acute ischemic stroke can we use the neuroprotection therapy? And recently, in the previous public clinical trials, we only used the neuroprotection therapy in the acute phase and maybe only once or several times. Maybe this is not enough. As we all know that the acute ischemic stroke caused the ischemia injury and the injury lasted for a long time, and the most intense change is during the first several hours, but after several hours later, the injury maybe also lasted for a long time, and the recovery of the estimated injury also lasted for a long time. So maybe in different phases of acute ischemic stroke, we should use different therapies and different neuroprotective agents and neuroprotective strategies. Also all of the FRONTIER trials get neutral results. And in the future, it provided a very helpful guidance for future clinical trials. And in future clinical trials that investigate the neuroprotective agents or neuroprotective therapies, and we can consider more comprehensive strategies to improve the patients who are treated with thrombectomy. Maybe with these strategies or with these steps, we can finally use the neuroprotection to improve the functional outcome of patients who are treated with thrombectomy.

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