Overview from the 2026 International Stroke Conference

A message from our sponsor. At Massachusetts General Hospital and Brigham and Women's Hospital, we're dedicated to using advanced research to improve outcomes for complex neurologic conditions. One system integrated neurologic care. This is Jose Merino, Editor-in-Chief of the neurology family of journals. The neurology podcast provides practical information to neurologists and other clinicians to help them provide better care for their patients. Thanks for listening and have a great week. Hello everyone, this is Andy Sutherland and I'm excited to be with you again for today's neurology podcast on one of our recurring series in the podcast, speaking with Seamot Chaturvedi on his impressions from the latest in the world of stroke, specifically the 2026 International Stroke Conference from the American Heart American Stroke Association. Seamot is the Director of University of Maryland's Conference of Stroke Center. He is also, I'm very excited to say, the most recent recipient at the International Stroke Conference of one of the highest awards that is given out by the American Heart Association, American Stroke Association, which is the David G. Sherman Lecture Award for those not in the world of stroke. This recognizes a prominent Stroke Physician, David Sherman, for Lifetime Achievement and Stroke Management Stroke Care Research and Clinical Care. Seamot, congratulations. We're so proud of you and proud to have you as a recipient of the David G. Sherman Award this year. Yeah, thank you Andy. It was a great honor and I enjoyed giving the lecture this year. Which we could also have as a separate podcast and talk about all of your life's work really in the world of secondary stroke prevention. But I know that you are eager as am I to discuss some of the latest trials presented at this year's ISC, particularly those that will be relevant to the care of stroke patients. Why don't we jump right in? I thought this year's conference was extremely substantive. There were a number of trials presented on stage, particularly the last day, the late breaking science day that really are in some ways going to be practice changing or inform how we practice. And we're going to start in the world of a cute stroke treatment as we often do with two trials. The first one that I wanted to ask you about and for us to discuss was called the option randomized clinical trial. This is an important trial because it is among the latest in a body of research now looking at the use of thrombolysis specifically in this trial to neck to place for patients with acute schemic stroke outside of our traditional early treatment window essentially four and a half hours to 24 hours from last note. In this trial, these were patients with non large vessel occlusion or at least in folks that didn't have proximal large vessel occlusions, those that would otherwise be going for individual thrombectomy and standard practice and seeing whether or not they would benefit from tonight to place in that extended time window. We should point out this trial was conducted out of China with a variety of investigators. And again, it was presented on stage of the ISC. So see might if you will, lead us through your impressions, maybe the primary results in your impressions of this side's important to clinical trial. The field of delayed window thrombolysis has gained renewed interest and it's gotten a little bit more complicated. Previous trials have shown and the timeless study was probably the best example is that in the delayed window, if thrombectomy is imminent, then there doesn't appear to be any benefit of giving thrombolysis. On the other hand, if you have a patient in the four and a half to 24 hour window who doesn't have a large vessel occlusion, could there be potential benefit of administering thrombolysis in undersurund physiologic parameters? And so in this study, they explored that topic and they included patients, 570 patients, a median age of 68 years, and the NIH qualifying range was 6 to 25. And all the patients were required to have perfusion imaging and they allowed a core volume up to 50 ml and a ratio of 1.2 at least. And in terms of the patients who were actually enrolled, they had a median NIH score of 7, majority had occlusions and the M2 portion of the middle cerebral artery or the anterior cerebral artery. And even though they included up to a core volume of 50, most of the patients had a very small core volume. And so that's important to highlight that these were not patients with moderate sized infarcts. They were patients with very little infarcted tissue at the time of entry. And the average time to randomization was about 12 hours after the patient was last known well. And so they looked at the 90 day outcomes with the connectoplase and they found that the excellent outcome was achieved in 43.6 percent of the connectoplase patients compared to 34.2 percent of patients who receive placebo. And so this was a significant benefit. There was about a 3 percent rate of symptomatic intracranial hemorrhage in the connectoplase patients, but no increase in death overall in the connectoplase group. This adds an important study to the mix. And it shows that in patients who don't have a large vessel occlusion who meet these physiologic parameters, there did appear to be some benefit of administering connectoplase. And so we need to incorporate that with the recent trials that have been done in this area and on a case by case basis, some patients could benefit. And so I would advise stroke teams to review this study and see if they want to jump in and treat some of these patients on a select basis. That latter point is really the key. First of all, it's worth noting that this is very exciting, the possibility that we have a medical treatment in patients who otherwise are not rising to that level of kind of immediate standard care for thrombectomy, but in whom we still have an option for reprofusion treatment. That's exciting in that there's a proportion of patients who are going to benefit, like you mentioned, at least within the context of this trial, those with small and far-cores, based on their perfusion imaging, have salvageable brain tissue, have at least moderate degree of severity of the stroke that they're having, and that there is a measurable benefit. The tricky part is how to implement this within our stroke systems of care, both from the standpoint of not all hospitals within our stroke systems, both of our institutions work with partner hospitals out in the region in the community, who may not have that immediate access for perfusion-based imaging to make these sort of decisions, to help triage these patients. And then, of course, does this change the expanse with which patients are eligible to be immediately alerted for a stroke or receive a stroke code, and does that put further strain on our emergency systems of care and our hospital-based stroke teams and so forth? What are your immediate thoughts about that? I'm curious. I know that we're in the process of having those conversations locally, as many folks are based on these data, and also some similar guidance in our recent stroke guidelines. Yeah, for those at comprehensive stroke centers, I would have a discussion with you referring hospitals as to, do they have availability of perfusion imaging, and then to review the study results with them, and say that this could be applicable to patients with mild to moderate strokes, who have a salvageable tissue, but it's not really going to be applicable for the patients with more severe strokes those patients still likely could benefit from thrombectomy, this is niche population, but there still could be some benefit. Exciting nonetheless, and if this is going to help us reach more patients and benefit them, and hopefully we can continue to implement these data in a organized way within our own regional local stroke centers and stroke systems. Moving right along, back to our patient population who are in that more severe category with large vessel occlusions who would be eligible for thrombectomy. There was another trial presented, the Choice 2 trial, and this is another sort of, in a body of clinical trials, looking to see whether or not thrombolysis or local, and importantly, in this trial, local thrombolysis. So inter-artial thrombolysis benefits, in addition to thrombectomy, patient outcomes. I believe this trial, CMAT was conducted in Spain, and again, it was also presented at the International Shirt Conference. What were your thoughts on the Choice 2 trial? One of the topics of interest in the acute stroke field has been that as the thrombectomy results keep improving, now 85 or 90% of our patients with large vessel occlusion, they can have a very effective re-canalization. On the other hand, the percentage of patients with excellent outcome in most studies has been between 30 to 40%. And so why do we have this disparity between the vessel being opened and yet the patient's not achieving excellent outcome? And there are a variety of reasons, but one hypothesis has been that the micro-circulation could still be obstructed and the procedure itself could be sending some MRI downstream, which are obstructing some of the smaller blood vessels. And so one concept, which Dr. Chamorro from Spain first introduced with the Choice 1 study, was what about after the procedure, giving inter-artorial thrombolysis in an attempt to try to open up some of the smaller blood vessels. And so in the Choice 1 study, they did show benefit with inter-artorial thrombolysis, but it was regarded as a preliminary study. And so now they reported the results of Choice 2, where they looked at patients who had excellent outcome with re-canalization, at least a tick-2B to tick-3. And these were patients within 24 hours of stroke onset, and they included patients with an Aspect score of 6 or above. And then the patients were able to be treated with up to 20 milligrams of the thrombolytic agent, and they enrolled 433 patients. Average age was 76, median NIH stroke scale was 15. And remarkably, almost 2/3 of the patients had preceding thrombolysis. And so not only did they have thrombectomy, they had preceding IV thrombolysis. And then on top of that, they got the inter-artorial thrombolysis. And so the average time to treatment was about 270 to 275 minutes. And then they looked at the 90-day excellent outcome with a modified rank in score of 0 to 1. And this was quite striking that the patients who received inter-artorial TPA had a 57.5% rate of excellent outcome compared to 43% with placebo. They did report no increase in interest-rebel hemorrhage, but there was a slightly higher all-cause mortality in the TPA group of 12% versus 6%. And it didn't appear to be due to cerebral hemorrhage. So the reasons were not totally clear, but hopefully they'll be more clear when the final paper is published. And they also reported they did a CT perfusion at 36 hours and found that there was less hypop perfusion in the patients who received the inter-artorial TPA. So overall, this was an exciting result. It showed about a 15% improvement with the inter-artorial TPA. But we should mention that there have been other trials in this arena and the results have been mixed. And we need to put this together with all the trials that have investigated local thrombolysis following thrombectomy. And then once again, stroke teams need to review the data and then see if they're comfortable embracing this as a potential new treatment option. That's an important caveat to that last point. And most of us who work with our interventional colleagues or indeed at the point of impact in performing mechanical thrombectomy, it stands to reason that if the mechanical manipulation or retrieval of a clot is incomplete or the dynamic of pulverizing a clot at fragments of it going downstream, historically what you'll hear from interventionalists is that they will make that choice of giving local thrombolysis and bringing amounts. In our local experience, I feel like it's often very small amounts. You mentioned they were able to use up to 20 milligrams of local malitic here but oftentimes one, two, three milligrams, little small amounts. People at least report to be effective. And what I like about this trial is one, it does show that approach is at least safe in patients who have also gotten systemic thrombolysis. And then they really did nice follow-up imaging to verify the physiologic effect of what they are seeing on their improved reperfusion. And then of course being able to associate that with their primary outcome which were substantial improvement functional outcomes. So any event, this at least continues to support that practice. But as you said, C.Mod, when you look at the entire body of literature, this is another area where folks will have to decide whether this is implemented as a default standard practice or sort of a continuum on a case-by-case basis. But exciting lesson, of course, this trial has not yet been published in the primary literature. So we'll look forward to that to get more details going forward. Okay, transitioning from acute stroke, which of course often gets a lot of the excitement at these meetings, particularly our International Start Conference in recent years, where we've made a lot of progress. What was exciting about this year's meeting is for the first time in a long time, C.Mod, we had a presentation on in the world of secondary stroke prevention that really got a lot of a plum. And that was the oceanic stroke trial. And before we get into talking about oceanic stroke, it's worth mentioning that this trial was at least supported in part by bear. Bear, this is a trial looking at a novel, a novel antithrombotic agent, a factor 11 inhibitor, which we can talk about. But they at least supported the trial with providing the study drug. As far as I know, they were not involved in the primary analysis or data gathering and so forth in the trial. And C.Mod, you had mentioned to me in preparation for the day that you do some consulting work with them, but also not involved in the data analysis or interpretation of these results. So we just want to get that out there in the open. But in any event, this was a really exciting trial. I don't want to steal your thunder. So I'm going to let you comment on what you heard about the presentation of those oceanic stroke trials. If you look at some of the individuals in the past who have had genetically low levels of factor 11, it's been observed that they have a decreased rate of thrombotic events without really a major increase in bleeding. And this new compound as indexian was administered 50 milligrams per day versus placebo. And they investigated patients with either stroke or high risk TIA, who could be enrolled within 72 hours of the last event. And then the patients were subsequently followed for up to 31 months. And the primary outcome was recurrent is Schemic stroke, but they also looked at major bleeding, stroke MI, vascular death as additional outcomes. And so finally, it was a large international trial with over 12,000 patients recruited. The vast majority, 95% were stroke and 5% TIA. One positive aspect of the trial is that they had a good mixture of stroke subtypes. About 40% were large vessel atherosclerosis. About 30% were a stroke of unknown cause. And about 20% were small vessel disease. The patients enrolled had a very mild strokes with a median NIH score of two. But about a quarter had a NIH score of a four to seven at entry. And close to two thirds of the patients had dual anti-playout therapy, and then the remaining had single anti-playout therapy. So the asinduction was given on top of either single or dual anti-playout therapy. In terms of the results, the asinduction group did have a reduced risk of recurrent stroke, 6.2 versus 8.4. So absolute difference of 2.2 relative reduction of 26%. There was also a reduction in stroke MI and vascular death. And there was a reduction in disabling stroke by about 1%. And from the bleeding perspective, it was impressive to see that there was no increase in bleeding. 1.9 versus 1.7 with asinduction compared to placebo. And intracranial hemorrhage was very rare in both groups. This is a significant breakthrough because this is really the first anti-thrombotic agent where it's been shown to have a decrease in recurrent stroke without an increase in bleeding. And we await the full published paper. This could be applicable to many patients that are seen in primary and comprehensive stroke centers. This is a significant advance forward. It's the first time I can remember in a long time that we had a new anti-thrombotic agent and secondary stroke prevention studied and presented that received a standing ovation at the International Stroke Conference. People are very excited about this. It was a large trial, lots of participants worth noting in the types of risk reductions were used to seeing on the acute stroke treatment side, the reperfusion side. You're not going to see those. And when secondary stroke prevention recurrent stroke prevention, or at least we were not used to seeing that. So these are fairly small treatment effect overall, but the fact that it was safe and there was a measurable treatment effect on the score of sort of 1% per year. Then once the drug is available to us, it'll no doubt be something that folks will be interested in utilizing to further modify that risk of secondary stroke. Now, important to note, I guess, some of the things when you mentioned, we're still waiting on the primary publication of this trial, but we anticipate that soon and we look forward to that. And then the drug is obviously not available to us now, but when things will be available on the market at some point. And then of course, there'll be a cost of the drug and so forth. So there are some steps remaining to see it fully available to us, but exciting nonetheless. So that was oceanic stroke. And then we had one last trial. So we wanted to sneak in here, Cmod, we were going to talk about an area that often gets overlooked with all of our, sort of, a scheme of stroke treatment, and that is the management or certainly the acute management of inter-serval hemorrhage. And there has been ongoing a very large multi-center trial called fastest. And fastest has been a big trial looking at the use of recombinant factor 7a versus placebo for the early treatment of spontaneous inter-serval hemorrhage as a hemostatic agent. And fastest was looking at patients presenting with ICH within two hours of symptom onset. And we were finally able to hear the primary results of the face-through trial presented at IC and see what we learned. Yeah, so we should mention at the outset that this isn't the first rodeo for recombinant factor 7a. It's been tested before and previously for inter-serval hemorrhage. It was shown to decrease hemorrhage expansion, but there was no improvement in clinical outcomes. And so here the investigators wanted to launch a very heroic and ambitious effort to treat within two hours of the ICH onset. And amazingly, they were able to do this in a fairly large group of patients, and they enrolled 626 patients from 93 sites. And the average age of the patients was around 60, about two-thirds were men, slightly more than half were of Asian background. And patients were treated at about 100 minutes after the stroke onset, which is really amazing. And the average ICH volume was about 17 mls, and the NIH stroke scale was median was 13. The majority were deep hemorrhages, and there was a positive spot sign, which is a sign on CT and geography in about a quarter of the patients. So unfortunately, once again, we see the pattern that the recombinant factor 7, it did lead to a decrease in a hemorrhage volume at 24 hours, but there was no clinical improvement. When they looked at the modified rank in of 0 to 2, the both groups were essentially identical at 46 or 45%. And also a little bit of a concern is that the thrombomolic events with recombinant factor 7 were about 5% compared to only 1% with placebo. So once again, we can say that there was no clinical benefit of recombinant factor 7a. However, the investigators believe that in patients who have a positive spot sign, there could be benefit. And so they're going to refashion the trial and continue on by including patients who can be treated within 90 minutes of hemorrhage onset or those with a positive spot sign. And so this will continue to be a very aggressive and ambitious treatment project to have ultra-early treatment for patients with ICH. And so we look forward to the next iteration of the trial, but to the at least this portion of fastest did not have clinical benefit. That was a little bit of a bummer to those who were eagerly awaiting this trial and still very confident in sort of the possibility of identifying fat or 7a or another hemostatic agent that helped us reduce that early impact of the patient. The impact of that early damage from interest or hemorrhage related to a demon local tissue damage and effects from the hemorrhage itself. This was, I will say, and you pointed out, C-Mod, there is this sort of nugget of excitement about the fact that if we can target or be highly selective on the folks that we can be more sure or actively bleeding at that early time point, IE, the ones that have that important CT and your gram spot sign, there was a signal there. That will continue to be something on folks minds and hopefully we'll be able to find a target population that would benefit from this treatment because we continue to need better treatments, a larger armament terium for folks presenting with acute interest or hemorrhage similar to the fashion with which we have expanded our acute eschemial stroke treatments on the hyper acute sides. So that's a lot. Certainly, again, this conference really had a wonderful program, a lot of new science going on all over the world, not just here in the United States, of course, but a lot of the trials we mentioned today are international trials. If you're not a down the wool strokeologist like C-Mod and myself definitely look out for some of the highlights that we mentioned today, seek the primary papers out when they're published and those that are already published and discuss amongst your own local stroke teams and systems of care, how we can better implement these to improve the outcomes for our patients. But for us today, this has been a fun discussion again with my dear colleague, Seemod Chaturvedi and we've been discussing the latest research presented at this year's HA ASA 2026 International Stroke Conference and again, a final congratulations to Seemod on receiving the latest David G Sherman Award for Lifetime Achievement and Stroke. Thank you for being here today and thank you to everyone out there for listening. Pleasure to join Indy. Thanks. This is Stacy Clark, your podcast editor. 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