ISC 2025 | Characteristics of mild strokes with a target occlusion: preliminary analysis of TRIMIS

We know that somewhere between 8% to 25% of patients with mild stroke, and mild stroke is defined by NIH stroke scale of 5 or under, have a target vessel occlusion. And just a little bit of background is why there’s this wide range of percentages of target vessel occlusion is because of how the target vessel occlusion is defined. Traditionally, target vessel occlusion was defined as a large vessel occlusion in the anterior circulation. So, of course, a smaller percentage of mild stroke, you know, patients who present with an NIH stroke scale of five or lower would have a large vessel occlusion. And the other issue is how we define time. So, majority of the original studies in in the mild stroke space included patients who presented under six hours from symptom onset. So that’s why when you look at the literature, there’s this wide range of percentages. But regardless of how the target occlusion is defined, we know from two decades of studies that presence of a target occlusion is a predictor of poor outcome in this population. Now, what to do in terms of acute therapies when it comes to acute reperfusion therapies is still unknown in this population. So presence of a target occlusion is an indication of poor outcome. So naturally, many studies in the space looked to see whether or not these patients, like their moderate and severe counterparts, will benefit from reperfusion therapies. So a number of large trials in this space has been conducted either in the IV thrombolytic space or mechanical thrombectomy. And when it comes to the issue of mechanical thrombectomy, a number of trials are also ongoing in this space still. And the issue is that many of the patients with mild stroke actually don’t conform to the inclusion and exclusion criteria of these ongoing trials. So that leaves an important gap, and that’s why basically large-scale international studies that are representative of the entirety of the population of mild stroke, and of course, representative of the contemporary endovascular practices needed, and that’s the background based on what we started basically designing TRIMIS and conducting the study. So TRIMIS stands for thrombectomy in mild ischemic stroke with a visible intracranial occlusion. TRIMIS was a multinational observational comparative effectiveness cohort. And it had two main aims. Aim number one was just exactly what I mentioned earlier to identify really the clinical and radiographic characteristics of mild strokes that present with a target occlusion, be the characteristics of their occlusion site or their clinical characteristics, and importantly, what time they present, and how these patterns conform to the inclusion exclusion criteria of the ongoing randomized trials. And the aim number two is the primary outcome of TRIMIS. That was the 90-day favorable functional outcome. It’s defined as MRS of 0 to 1, and a number of secondary outcomes, including ordinal shift in MRS at 90 days, functional independence, MRS of 0 to 2, and a series of safety outcomes, inclusive of symptomatic intracranial hemorrhage and 90-day mortalities. What I presented at the International Stroke Conference was results, the preliminary results of TRIMIS, which is that aim number one. And the primary outcomes of TRIMIS is still unknown, and we’re in the final stages of analysis and hopefully will present it at the next large international forum. So in terms of what TRIMIS showed, again, this is the preliminary results on the aim one. So first off, TRIMIS was a large international collaboration. Again, these are observational data that came to us from January 2018 to September 2024. We had 40 centers providing data from 17 countries in nine regions in the world and four continents. So we are really truly in international collaboration. A total of 5,426 patients with mild stroke and target vessel occlusion were included for this preliminary analysis, for the primary outcome. We will have a little more because three of the sites were still closing data. and basically didn’t get to the ISC presentation. So very large population. And in terms of our primary finding of what percentage of these patients were treated with maximal medical management, what percentage received endovascular therapy, and importantly, we dichotomize endovascular therapy to immediate endovascular treatment. Those are the patients that present with mild neurological symptoms and a target occlusion. And at the discretion of the treating physicians, they underwent immediate endovascular thrombectomy. And all of us as practicing neurologists know that a percentage of patients with mild stroke are not treated with endovascular thrombectomy early on. And they are observed, and majority of them are observed with maximal medical therapy. And then at a later time frame, most likely because of further neurological deterioration, they then undergo a rescue endovascular therapy. So in TRIMIS, we were interested to see in routine practice what percentage of patients undergo thrombectomy immediately versus rescue therapy. And here are the preliminary results. Of all patients, 45% were treated with medical management. That is inclusive of intravenous thrombolysis. 46.3% underwent immediate endovascular therapy and 7.9% rescue. And of course, we looked at a number of clinical characteristics across these three categories of patients with mild stroke. The median age was 70. This is in keeping with what was published in this space before. We had 46% of our patients were female. Not surprisingly, the majority of these patients had a good functional baseline, so that’s pre-morbid modified ranking of zero to one and really the distributions of traditional vascular risk factors were basically similar across the three categories of maximal medical therapy, immediate endovascular treatment, and rescue endovascular treatment. One of the things that are sort of important finding of this data from TRIMIS was what percentage of these patients had a large vessel occlusion. Again, traditionally large vessel occlusion is considered anterior circulation, large vessel occlusion that is distal, I say terminus occlusion or M1 occlusion, and 29% of patients in TRIMIS had that pattern of occlusion, so anterior circulation LVO, and unsurprisingly, a higher proportion of patients who underwent immediate endovascular therapy had an anterior circulation LVO. In contrast, 30% of total TRIMIS population had an M2 occlusion. So these are medium vessel occlusion, again, in the anterior circulation. And the percentages were not that different between the three categories. But again, more or higher percentage of patients in the immediate endovascular thrombectomy and rescue endovascular thrombectomy had an M2 occlusion as compared to those who were treated with best medical management. I want to mention that large vessel occlusion in the posterior circulation obviously is important to note. Six percent of TRIMIS patients had a basilar occlusion. Again, the percentages were a lot higher in those who underwent immediate endovascular thrombectomy or rescue EVT as compared to those who were treated with the best medical management. And these were all expected but very important findings of TRIMIS. Now, one of the things that we’re very interested in identifying is, again, time from symptom onset. And importantly, seeing that many of the randomized trials in the mild space only include patients under six hours from symptom onset, we were interested in looking at what percentage of patients with mild stroke and target vessel occlusion present under six hours. And that’s good news from TRIMIS because 72% of the entirety of TRIMIS cohort presented under six hours, which is an important finding, again, from this large observational study as we look to design more and more trials in the acute space for mild stroke. Now, the next important sort of finding was to see what were the positive predictors of immediate endovascular thrombectomy. So what were the characteristics of patients that came to the hospital and then immediately received an endovascular thrombectomy? And again, we detailed all of those, but the highlights are if you presented with an anterior circulation large vessel occlusion, so that’s distal terminus ICA M1 occlusion, they were twice more likely to have been offered immediate endovascular thrombectomy. Again, unsurprisingly, if their median NIH stroke scale capped under 5, but they’re within 0 to 5, they had an arrival NIH stroke scale that was higher, they were more likely to receive immediate endovascular thrombectomy. Or even if their NIH was mild, but their symptoms were perceived to be disability producing, again, that was an independent predictor of receiving endovascular thrombectomy. Another interesting finding from the study was looking at diversity of practice. Of course, we have, as I mentioned, 40 centers from four different continents in the world. And it was very nice to see that though the guidelines are very similar across from Europe, North America, Asian guidelines are similar in this space, but the practice pattern is so different. For instance, patients that presented to European sites were more likely to receive immediate endovascular thrombectomy, which really emphasizes that when you are in the outskirts of the guidelines and the gray zone of the guidelines, practice patterns could be very variable. Now, one final finding of this aim one of TRIMIS was what percentage of patients with TRIMIS were eligible for ongoing randomized trials. And we gave some examples. For example, ENDOLOW is an ongoing randomized trial here in the United States and, of course, in some European countries where they include patients that are mild by NIH stroke scale definition presenting under eight hours with a ICA M1. And originally, ENDOLOW included M2 occlusions. 36% of TRIMIS patients conformed just to these few inclusion criteria of ENDOLOW. Of course, any randomized trial has a lot more inclusion and exclusion criteria. We all know that ENDOLOW went through a second iteration where M2 occlusions were no longer considered eligible for the trial. So now only including under eight hours presenting mild strokes with ICA M1 occlusion. And when you look at that population, only 16% of TRIMIS patients conform to those inclusion criteria. Another important trial that was just presented at the ISC, that’s ESCAPE-MEVO trial that looked at patients with medium or distal vessel occlusion and that when you looked at the inclusion criteria of ESCAPE-MEVO, again, 38% of TRIMIS patients conform to just time and occlusion site inclusion criteria. So in summary, the preliminary results of TRIMIS is very informative in that it shows that only a third of patients with target vessel occlusion presenting with mild neurological symptoms actually have an anterior circulation large vessel occlusion, which is an important inclusion criteria for the majority of trials in this space. And most of mild strokes don’t conform to the inclusion exclusion criteria of the ongoing randomized trials and of course gave us a lot of indications that what are the predictors of currently undergoing immediate endovascular thrombectomy as we await more studies in this space. And as I mentioned earlier, the primary results of TRIMIS will be presented hopefully at the next international meeting, which would be the World Stroke Conference.

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