Transcript: HelixTalk #196 - Stretching the Stroke Clock to 2026: A Brief Review of the 2026 Acute Ischemic Stroke Guidelines Episode ID: 230 Generated: 2026-07-24 14:14:41 ------------------------------------------------------------ [00:00] (Music) Speaker 1: Welcome to HelixTalk, an educational podcast for healthcare students and providers covering real-life clinical pearls, professional pharmacy topics, and drug therapy discussions. Speaker 2: This podcast is provided by pharmacists and faculty members at Rosalind Franklin University College of Pharmacy. Speaker 1: This podcast contains general information for educational purposes only. This is not professional advice and should not be used in lieu of obtaining advice from a qualified healthcare provider. Speaker 2: And now, on to the show. (Music) Dr. Sean Kane: Welcome to HelixTalk, episode 196. I'm your co-host, Dr. Kane. Dr. Khyati Patel: And I'm Dr. Patel. Dr. Sean Kane: And I'm so excited for today's episode, which is entitled Stretching the Stroke Clock to 2026: A Brief Review of the 2026 Acute Ischemic Stroke Guidelines. And for today, we're really talking about these new 2026 AHA/ASA guidelines. And to help us do that, we have Dr. Rachel Neu here. So Dr. Rachel Neu, do you want to kind of introduce yourself to the HelixTalk audience? Dr. Rachel Neu: Sure. It's been a while since I last came on board. So my name is Dr. Neu, and I am one of the clinical faculty here at RFU College of Pharmacy. So with my position, I pretty much have a split position. So 30% of my time I'm teaching here at the College of Pharmacy, and then 70% of my time I am practicing as an internal medicine pharmacist at Advocate Lutheran General Hospital. Dr. Sean Kane: Wonderful. And, you know, as we mentioned, today's episode focuses on the 2026 early management of acute ischemic stroke guidelines. And the last update was 2019. So we're now seven years since our last update, so probably time for a new document to come out. Dr. Khyati Patel: Right. And new and longer. So there is like 119 pages. Obviously, we're not going to cover all of it, but we have a plan. And the plan is a five-pronged approach. We're going to answer or focus on five sections. Dr. Sean Kane: And for the audience that wants to dive a little bit deeper, if you go to helixtalk.com, again, this is episode 196, you'll be able to get a link to the full guideline document, the 119 pages of glory, if you're interested in that. And we've really tried to pick these five sections that we feel like are most relevant mostly to practicing pharmacists, but just clinicians in general versus the uber-specialized neurologist, for example. Dr. Khyati Patel: Agreed. Dr. Sean Kane: So Dr. Neu, what five sections did we come up with for today's episode? Dr. Rachel Neu: All right. So we're going to start with IV thrombolysis. And then we're going to talk about antiplatelet therapy. And then we're going to move on to endovascular treatment or thrombectomy, blood pressure goals, and then last but not least, the blood glucose goals as well. Dr. Khyati Patel: Perfect. Sounds very relevant. Right. Let's dive right into it. Dr. Sean Kane: Well, why don't we start with IV thrombolysis, also abbreviated as IVT. And the big deal here is tenecteplase. So Dr. Neu, can you kind of orient the audience a little bit to what the guidelines used to say and what is big or new or different about tenecteplase? Dr. Rachel Neu: Yeah. So I think the biggest thing about this new guideline is that tenecteplase is now FDA approved. So in the past, we were using it almost like an off-label medication. So in the past in the guideline, if you were to look at it, it's all about alteplase. And that's, you know, for good reasons because alteplase has been around in the market for a long time. But more and more evidence are coming out supporting the use of tenecteplase. And I think with the new guideline, it formally got introduced into the guideline as a, you know, standard of medication almost. Dr. Sean Kane: I think what's really important is that the guidelines don't say it's better per se, although if you talk to different people, there are some trials about maybe better, definitely more convenient. But the guidelines say it's equally preferred to alteplase, which I think is important to note how it tiers the IV thrombolytic approach. Dr. Khyati Patel: Yeah, agreed. So what is more attractive about tenecteplase aside from obviously efficacy being good and the safety being equal, what is attractive here? Dr. Rachel Neu: Honestly, I think the biggest selling point is how easy it is to use tenecteplase over alteplase. Like alteplase has to be given, you know, like as a bolus dose first and then you have to hang the bag for about an hour. But tenecteplase is pretty much like an IV push over seconds. And I think that's the biggest selling point. You don't have to set up a pump, you don't have to set up lines and things like that. Dr. Khyati Patel: So easier administration. Dr. Rachel Neu: Mm-hmm. Yeah. Dr. Sean Kane: In terms of dosing, so the guidelines recommend 0.25 milligrams per kilogram, maximum of 25 milligrams. So the 100 kilo patient and above is going to get that capped dose. And Dr. Patel, I think we should just mention that we were ahead of the game a little bit. So October 2023, we actually did a HelixTalk number 172 on this topic. Dr. Khyati Patel: Yeah, that feels not too long ago, but long ago, I guess. Dr. Sean Kane: So in that episode, we talked about how alteplase is the recombinant DNA version of human tPA. But tenecteplase is different. Dr. Neu, how is it different or chemically what is the difference between the two molecules? Dr. Rachel Neu: I think they're pretty much similar. The only difference is pretty much like the three amino acids differences between the two of them. And that pretty much render the tenecteplase a longer half-life and then a higher fibrin selectivity as well. Dr. Sean Kane: And let's just pause and think about that for a second. Three amino acids, so that's, you know, three codons or nine DNA base pairs confers a dramatically different half-life in your body for this medication or protein, right? Like this is crazy to think about such a small change can then infer this big pharmacokinetic difference, right? Dr. Rachel Neu: Mm-hmm. [05:15] Dr. Khyati Patel: Wow. And then the reason for this equally preferred recommendation is because when looking at the efficacy versus safety, tenecteplase was found to be at least as safe and effective. Although, as you mentioned, Dr. Kane, there might be some studies showing a little bit more benefit over alteplase. Dr. Rachel Neu: Yeah, I'm surely looking forward to, you know, seeing more real-life, real-world data, like meta-analysis, like looking at the use of tenecteplase and see if it's actually faring better than alteplase, potentially. Dr. Sean Kane: And I'm glad you brought that up because what you don't really capture or probably don't capture well in the randomized control trials is the dosing errors that may happen. And it's not even so much a calculation error with alteplase. It's the fact that you have the bolus plus the infusion. And then the thing that people often forget about is that when you hang your infusion, your IV tubing has, let's say, 10 to 20 mLs or whatever the content is of it depending on its length. You have to then hang saline after that to kind of flush the rest of the tPA through the line. And stuff like that, in terms of generalizability and making sure everyone knows those things, like you would assume that they do, but we make med errors all the time, right? So stuff like that probably isn't well captured in randomized control trials where it's very regimented versus in an institution where you have a new nurse or a new pharmacist that hasn't given tPA before and they don't know some of these things. Like it's more likely that errors can happen that way. Dr. Rachel Neu: Mm-hmm. Dr. Khyati Patel: So that said, Dr. Neu, which one are you using in your practice at Advocate? Dr. Rachel Neu: So personally, because I work in the internal medicine floor, it's not something that I deal with all the time. But we have switched our preference, like formulary preference to tenecteplase, I want to say maybe like a year or two ago. So we were using it off-label at that time. So all stroke cases now pretty much are getting the tenecteplase, but we're still using alteplase for other indications as well. Dr. Khyati Patel: Makes sense. Dr. Sean Kane: So let's talk about the tPA window or the IV thrombolytic window. You know, when I was in school, when the dinosaurs apparently roamed, the classic window that we learned was three hours. And then that window got extended because there was a trial saying, well, maybe up to four and a half hours in very selected patients. And then that extended window eventually we said, well, maybe we don't have as many selected patients in that extended window anymore. Maybe more people can qualify that were outside of that original trial. And that's kind of where my brain left off in terms of where the evidence has been and where the guidelines have gone. Can you comment on, we'll start with the three to four and a half hour window. It didn't change, but I think it's worth mentioning what the guidelines have historically said about that. Dr. Rachel Neu: Yeah, for sure. I think, you know, with the trial like you said, with the trial that looked at the expansion of the, you know, alteplase use beyond three hours, they were looking at very selective patients. So for instance, they were looking at patients younger than 80 years old. These patients should not have a history of both diabetes and stroke in the past. I think there's also one that actually says that they should not be on any oral anticoag as well. And the NIHSS score has to be somewhat reasonable. So less than 25 is what the cutoff is. So that, you know, those set of criteria was in the old guideline too, under like the eligibility and the indications as well. With the, with what we're using in the clinical practice though, I think it really depends. So for instance, where I practice for instance, going through the inclusion and exclusion criteria of tenecteplase and alteplase, the only thing that kind of like linger around or got included in our inclusion exclusion criteria is pretty much the NIHSS score. Everything else is pretty much up to the provider and it's not actually in our, you know, like inclusion exclusion specifically. Dr. Sean Kane: So kind of a, it's not a hard and fast rule. We acknowledge that the, I guess that would be a phase three trial in this like newish patient population that they had certain exclusion criteria, but then as time went on, people became a little bit more comfortable not excluding some of those patients that would have originally been excluded in the trial. Dr. Rachel Neu: Yeah, I agree. Dr. Sean Kane: So then what is new or different with the 2026 guideline update? Dr. Rachel Neu: I think the biggest thing is the further expansion. So now we're not just, you know, like limiting it to just four and a half hours. We're going up to nine hours. Dr. Sean Kane: So Dr. Neu, nine hours is a lot different than four and a half or three hours. Who can qualify for this now extended, extended window of nine hours? Dr. Rachel Neu: Yeah. So I think other than the nine hours as one of the criteria, I think the biggest things that we're looking at is, you know, specifically for patients with salvageable ischemic penumbra on brain imaging. So we're pretty much looking at, you know, the middle, which is the core. And the core is pretty much like irreversibly infarct cells that we're not trying to save anymore. And then surrounding it is what we call the penumbra. So this is like hypoperfused cells that, you know, when we're giving fibrinolytic agents, we're really trying to maximize saving this penumbra and minimize the core expansion. So if they show that on imaging and if they present within the nine-hour timeframe, then these are the potential candidates for fibrinolytic agent as well. [10:01] Dr. Sean Kane: And almost intuitively that makes sense that if you have an imaging method to show that you have definitely dead brain tissue, but then around it, maybe brain tissue that could be saved, you're almost giving the drug to try to save that salvageable brain tissue. And you're only doing that because the brain imaging said that there's something to be saved versus someone who definitely doesn't have that salvageable brain area and it's kind of not worth it then because you know that that area is definitely dead and it's not going to recover. Dr. Rachel Neu: Absolutely. Dr. Khyati Patel: So that's one thing to look at the brain imaging and figure out, you know, what's salvageable, what's not anymore. But then we used to do that calculation, like that three-hour window or 4.5-hour window when we consider, how does this work now with the nine-hour window? Dr. Rachel Neu: That's actually very interesting too. So in the past, like if you know exactly when it starts, that's, you know, the start of the clock essentially. And then we have, you know, what, how we calculate the last known normal essentially. So if a patient wakes up with, you know, stroke symptoms, we would say that the last known normal per the old guideline was before the patient went to bed. So that's the last time we saw the patient as normal. So that's the last known normal. With the new guideline though, they pretty much reset in terms of the patient waking up with symptoms. Their nine hours, no, the starting point actually starts with the midpoint of the sleep. Dr. Khyati Patel: So when, if they go to sleep at 10 o'clock and woke up around, let's say six. Dr. Rachel Neu: So that's like a eight hours of sleep. So the midpoint would be four hours. So essentially it starts at two. And then if you were to extend nine hours, they can have up to like 11 o'clock in the morning as long as they present within that timeframe, they may still be eligible if they show, you know, the penumbra on imaging. Dr. Sean Kane: And I can hear the audience saying, well, does that really happen that often that people get a stroke in the middle of the night? And actually, yes, this is like really, really common. If you think about it, you spend a third of your life sleeping, if you get your eight hours of sleep, right? But lots of patients wake up with stroke symptoms and their last known normal is when they went to bed. So this is potentially going to expand the window out for a lot of patients that would normally not have been eligible because they went to bed at a normal time, they woke up at a normal time. Because basically with the old rule of four and a half hours, if you fell asleep normal and then you woke up with a stroke, you're not eligible unless you only got four hours of sleep, right? So this is actually a really big deal. Dr. Rachel Neu: Yeah. Dr. Khyati Patel: Potentially qualifies a lot more patients than before. Dr. Rachel Neu: Yeah. And I think that's the general outlook of the new guideline too. I feel that they're really stressing like, you know, there's actually a lot of benefits to using the fibrinolytic agent overall and it should really be considered for, you know, most people unless they really meet certain contraindications. Dr. Sean Kane: And what's so interesting about this is way back, and we're talking like mid-90s, we used to have a lot of controversy about the efficacy of getting thrombolytics. We used to have a drug called streptokinase that was used instead of alteplase and stuff like that. And that had some issues with it. So really like in the past 30 years, let's say, there's been a big shift from, you know, we think tPA is good to tPA in selected patients to expanding the window more and more and more. And we're kind of getting to the point where we're recognizing that probably, especially with more advanced imaging where you can actually look at the brain and say whether it's kind of worth it to expose them to something that causes bleeding, that window keeps expanding, which I think is probably a good thing, right? Dr. Rachel Neu: Mm-hmm. Yeah. Dr. Khyati Patel: Yeah, and at the end of the day, it's all about benefits versus risk, right? So if more patients qualify and can benefit from improved, you know, daily life function and stuff and recovery, then as opposed to the bleeding, then why not, you know, make those patients eligible. Dr. Rachel Neu: Yeah. Dr. Sean Kane: But of course, there's going to be people who don't qualify. It's not new, but something that was better clarified in the guidelines is a mild non-disabling stroke. So Dr. Neu, was this not defined previously or did they use that terminology previously? Dr. Rachel Neu: They did use the same term. So the mild non-disabling stroke is not something new. But if you were to look at the old guideline, it also says in parentheses, this means NIHSS score of zero to five in the old guideline. In the new guideline, the NIHSS score is pretty much removed. It just pretty much says mild non-disabling stroke. So it's really not dictated just by the NIHSS score. So it's really how the patients, you know, like perform and how they are, you know, their symptom, how their symptoms are essentially after a stroke. And I think I really like one of the examples that they give within the new guideline too. So they're pretty much showing that let's say if a patient presents with severe aphasia, so if you were to calculate the NIHSS score, it might be a two. You know, like it seems trivial, but, you know, having a severe aphasia can be disabling to some people and, you know, they might not be able to go back to their daily living, for instance. So in that case, the patient can and should be considered for fibrinolytic agent. [15:00] Dr. Sean Kane: And I think one big strength of that is it's a very like patient-specific decision, not just, it's almost too difficult to narrow down the severity to a number of the NIH stroke scale. And granted, like that stroke scale does give you a general idea of severity, but especially at small numbers between a three and a four, that could actually be a really big difference depending on how you added that extra point or what symptom got you that extra point. So I think this is probably a big win in terms of a more holistic approach of like, is this a bad enough stroke that you're willing to take the risk of an increased risk of bleeding because the potential upside of reversing that neurologic deficit is worth it, you know. Dr. Rachel Neu: Mm-hmm. Dr. Khyati Patel: So what do these patients have then? If they have mild non-disabling stroke and they shouldn't get fibrinolytics, then what are their options? Dr. Rachel Neu: Um, so there is the dual antiplatelet therapy that can be used for that specific group population. And I think we're going to be covering that later on too. Dr. Khyati Patel: Yep. Got it. Dr. Sean Kane: And I think just for completeness sake, it's not new, but there are definitely exclusions to IV thrombolytics that we should probably just mention. So there is a ton of patients that have strokes that don't qualify for IV thrombolytic regardless of that time window that we talked about. But there's other conditions or other reasons that they couldn't get tPA. So what would some of those be? Dr. Rachel Neu: Um, so if they have intracerebral hemorrhage, that's for sure. Um, and then we have certain absolute contraindications like, you know, those presenting with moderate to severe brain trauma or neurosurgery within the last 14 days or infective endocarditis, for instance. Dr. Sean Kane: And then we have some relative contraindications that generally you're not going to do it. So that would be if they had a DOAC within the past 48 hours, stroke within the last three months, major non-cranial surgery within the past 10 days, STEMI in the past three months. All of these are relative contraindications where you typically wouldn't do it unless there's some nuance or something different about that scenario. Dr. Khyati Patel: Uh, and then the guidelines kind of providing sort of examples of cases where providing IV thrombolytics will lean more towards the benefit than the risk. And those cases will be like, maybe they have a remote history of GI bleed. Um, we are not really sure about the stroke diagnosis, but it mimics like stroke. So like considering other differentials like an MS flare or something. Um, and then looking at like unruptured intracranial aneurysm. So in those cases, um, maybe you want to consider IV thrombolytics because the benefits do outweigh the risks. Dr. Sean Kane: And institutions are going to have checklists and they're going to, um, generally show absolute contraindications versus relative contraindications. And for the most part, the neurologist, whoever is on call for the stroke is going to make the final, final decision. But as pharmacists, it's always nice to know like what are the typical criteria that are going to rule you in or out of getting tPA. Dr. Rachel Neu: Yeah, totally agree. Like when we're assessing, you, you would want to bring out, you know, those things. But ultimately, like Dr. Kane said, it's going to be, you know, up to the provider to decide whether or not this patient should be getting it. Dr. Sean Kane: Well, why don't we move on to antiplatelet therapy. What hasn't changed? So we, uh, we talked about dual antiplatelet therapy that we'll get to in a second, but what are kind of the key tenets of antiplatelet therapy for a stroke patient? Dr. Rachel Neu: Um, so essentially antiplatelet will be the primary antithrombotic, um, agent if a patient is presenting with a stroke that is of a non-cardioembolic source. So, you know, if we're looking at EKG, there's no A-fib. We're looking at echo, there's no like LV thrombus, for instance. In that case, that's what we call like a non-cardioembolic stroke. And so we're thinking about platelet in that case. Dr. Khyati Patel: And the agents commonly used are, are aspirin or other P2Y12 inhibitors like clopidogrel, um, and the combination of aspirin plus the dipyridamole. Dr. Sean Kane: And in the case of each of those, the loading dose or lack of a loading dose is important because later on we'll talk about when loading doses are sometimes used. With aspirin, we do give a loading dose and then the recommended dose is typically 81 milligrams a day. With clopidogrel, there is no loading dose and then we give the normal maintenance dose. And then with aspirin and dipyridamole, which is brand name Aggrenox, there is no loading dose and then you take one capsule twice a day, which is an ER capsule. So generally no loading dose except for the aspirin, which you're going to give 160 to 325 milligrams, uh, when they come in. Dr. Khyati Patel: And then we talk about the dual antiplatelet therapy. This is kind of what we discussed earlier, reserved for patients who have that mild disabling stroke. So when do we consider it, you know, what's the length of therapy for that? Dr. Rachel Neu: Yeah. So again, those are really for those who are not like a candidate for a fibrinolytic agent. Um, so mostly for mild non-disabling stroke. Um, so we're looking at potentially using a dual antiplatelet. There are a few options here. You can use like aspirin and clopidogrel. You can use aspirin and ticagrelor. And it can be a duration of 21 days versus 30 days depending on which trial that you look at, um, that led to the approval of both. [20:00] Dr. Khyati Patel: And then this is where your comment about loading dose will come in, Dr. Kane, right? Dr. Sean Kane: Yeah. So in these cases when you're doing DAPT therapy, the trials used a loading dose for these patients, probably because many of them didn't get tPA. So for clopidogrel, you're going to give 300 or 600 milligrams. Different trials use different loading doses. And then your maintenance dose the following day. And then with ticagrelor, you give the typical loading dose, which is 180, and then the normal maintenance dose after that. So for the most part, um, especially the historical studies, and we'll talk about some new data in a minute, this regimen was given very early on within the first 24 hours of stroke onset. So again, typically we, if you get tPA, you're not getting antiplatelet therapy within that first 24-hour window. So these again would be the mild non-disabling stroke on average that wouldn't get tPA and we're giving them the loading dose followed by a maintenance dose of either aspirin and clopidogrel or aspirin and ticagrelor for the 21 to 30 days. Dr. Khyati Patel: So we kind of talked about what is DAPT therapy, who qualifies for it, you know, how it's targeted. Are there any other criteria besides looking at that mild disabling stroke or in some cases looking at that NIHSS score that we look at to see who qualifies for it? Dr. Rachel Neu: Yeah. So, you know, like for acute ischemic stroke, we typically look at the NIHSS score to determine how severe a patient's stroke is. The higher the number, the worse the severity is essentially. And then if we're looking at like TIA, which is like a transient ischemic attack, so essentially this is not a full-blown acute ischemic stroke just yet. It's almost like a warning stroke. Um, so if a patient presents with that, we're going to be looking at, um, what we call the ABCD2 score. Um, it pretty much predicts like what is the chance of somebody having an acute ischemic stroke, you know, within two days up to like 90 days after the initial event. Um, so we can use those score to dictate like who are the candidates. So for somebody with a mild non-disabling stroke, for instance, we're looking at what we call the sweet spot. So if they have like a NIHSS score of three or less for a minor ischemic stroke, or if they have a high risk, you know, like a TIA defined as ABCD2 score of at least four or more, then those are the candidates, at least those are, you know, based on the old guidelines. Dr. Sean Kane: And then Dr. Neu, one thing I like about this is it, uh, for students, I think, especially when I learned this, I just memorized the numbers, right? But I didn't fully understand why. So as you mentioned, that lower severity of stroke number, the NIH score is telling us that these, this is a milder type stroke. And the reason that matters is that there was data where they tried dual antiplatelet therapy in more severe strokes and it didn't work very well. Those patients were more prone to bleeding. So kind of the benefit of the dual antiplatelet therapy was offset by the bleeding risk. So that's why we're picking the more mild stroke patients. And then the ABCD2 score, we're trying to pick out the patients that are the highest risk of having a stroke very soon. So, uh, if you think about it, the alternative to DAPT is just getting aspirin or clopidogrel. So we're giving extra antiplatelet therapy to these patients. So we're trying to pick out the patients that are more likely to have a stroke in a week or in two weeks or even tomorrow, right? So giving them a little extra makes sense because they're at a higher risk than someone with a lower ABCD2 score. Dr. Khyati Patel: So Dr. Neu, what, what changed in regards to the DAPT therapy? Dr. Rachel Neu: Um, so I think the biggest change is that we are including a higher number of NIHSS score. So like, like we talked about previously, it was limited to patients with NIHSS score of three or less. But now it is expanding to also include patients with NIHSS score of four or five. Um, so this might be still the patients who are not eligible for, you know, like a fibrinolytic agents just because they most likely will be presenting with a mild non-disabling stroke. And I think that really came from, you know, the trial that just missed the cutoff for the 2019 guideline. It came out, I think it's 2020 that actually looked at this patient population and actually showed positive results, you know, looking at the use of dual antiplatelet in this patient population. And now it's just formally made into the guideline based on the trial. Dr. Khyati Patel: Yeah. Dr. Sean Kane: And then what about timing? So we talked about most of the original data was basically within the first 24 hours. So a very acute management in terms of giving the dual antiplatelet therapy. Do we have any new evidence there? Dr. Rachel Neu: Yeah. So, so in the past, like Dr. Kane mentioned earlier on, um, the sooner the better. So we're looking at less than 24 hours if possible or within 24 hours window. But with the new guideline, they're also looking at potentially, you know, like starting this dual antiplatelet therapy up to 72 hours. But I think one of the additional, um, criteria that they should have, where if we're to use it within the 72 hours, is if they can tell for sure or if they presume that the stroke or the TIA is due to at least 50% of the atherosclerosis. [25:00] Dr. Sean Kane: So Dr. Neu, in short, really the big update is an expansion of that NIH stroke score can be four or five instead of three or less. And then up to 72 hours with a couple caveats in terms of some imaging or high suspicion that it's from atherosclerosis with a, like a high-grade lesion. Dr. Rachel Neu: Mm-hmm. Dr. Khyati Patel: So that moves us from that pharmacologic interventions to more like mechanical interventions like the endovascular thrombectomy, also known as EVT. Um, so in general for the audience, EVT is where they go in with a catheter and a stent and then try to remove or unclog the artery. So remove the clot. Sometimes it is done along with the, with the thrombolytics that we talked about too, but sometimes it's just done mechanically. Dr. Sean Kane: And I would say in the last probably five-ish years, this has been an area of like explosion for research because what we've really seen is that one, the window for these patients is much longer versus especially versus the old four and a half hour tPA window. But then two, the patients that do receive this intervention, they actually have really good clinical outcomes. So it's not like a question mark of like, is it helpful or not? It's clearly beneficial in selected patients that qualify for EVT. Dr. Khyati Patel: And I'm sure like the IV thrombolytics, there are probably qualifying criteria. What are they, Dr. Neu? Dr. Rachel Neu: Um, so like, you know, the thrombolytic agent, like you said, time is brain. So time is always essential. Um, we want to do it as soon as possible. Um, so the other thing that we want to take a look at is make sure that the stroke symptoms are not too mild to begin with because this is pretty invasive. We're pretty much going in and try to retrieve like a clot that can be retrievable. Um, yeah, so we're looking at potentially like NIHSS score that needs to be six or higher. Um, so the second thing that we think about is the modified Rankin score too. So this is a score that pretty much look at how disabled a patient is prior to the stroke itself. Um, so the lower the score, the better it is essentially. If a patient is a candidate for EVT, then ideally we want the patients to have the modified Rankin score of zero to two. Um, so essentially no disability to a mild disability. Dr. Sean Kane: And that kind of intuitively makes sense that if prior to the current stroke a patient had, they had an old stroke that made them very disabled, there's probably not much room for improvement if you undergo EVT to try to fix the current problem from their current stroke. And if we fix the current problem, they can go back to a fairly good baseline versus someone who never had a good baseline to begin with, there's not a lot of opportunity for improvement there. Dr. Rachel Neu: Mm-hmm. Dr. Khyati Patel: And I believe they're also looking for, uh, on the brain CT, they're looking for a particular parameter too, and then there is a score associated with that as well. Dr. Rachel Neu: Yeah. So, you know, on a head CT, you can pretty much like calculate what the patient's ASPECTS score is. Um, so the ASPECTS score pretty much quantifies the degree of ischemia on the brain imaging. Um, like a lower score will be the worst. So a score of zero will be the worst of all where there's the most ischemic damage that's seen on the brain CT. And a score of 10 will be the best where there's no ischemic changes at all. Dr. Sean Kane: And again, a lot of the original data looking at this, they tried to pick out brains that would be more likely to benefit from EVT. Meaning if the patient had an ASPECTS score that was really low, meaning lots of brain damage that was already done, there's probably not a lot of salvageable tissue there. Therefore, probably EVT isn't going to be as helpful. So a lot of the original data looked at ASPECTS scores that were six or higher. But then there have been newer trials that looked at ASPECTS scores all the way down to zero and they still included patients and they still showed benefit. So generally speaking, the higher the ASPECTS score, the better the benefit probably is, but it's definitely not an exclusion if your ASPECTS score is too low, meaning that there's a lot of brain damage. It's not necessarily a reason to not do EVT. Dr. Khyati Patel: And again, this is where we individualize the therapy, right? And the plan for the patient. So it's a team approach here. Um, Dr. Neu, what is that timeline for consideration of EVT? Dr. Rachel Neu: Yeah, like time is brain. So the sooner the better. Um, so the best evidence with EVT is within six hours of onset of symptoms. Um, but it is reasonable to extend the duration like beyond the six hours that we want. Um, but only in selected patients. [30:00] Dr. Khyati Patel: So that brings up to the next two kind of focus areas, really important for practicing pharmacists too, like what are the blood pressure goals and what are the blood glucose goals. So let's dive into what are the blood pressure goals recommendations and have they changed or not? Dr. Rachel Neu: Yeah, so the blood pressure goal is pretty much the same. Not much has changed. Um, so I think it's definitely worth, you know, talking about it because it's one of the things that we focus on, you know, when we're assessing whether or not a patient is a candidate for fibrinolytic. And now that you have received that, what is your goal and stuff like that versus a patient who is not a, you know, candidate at all. Dr. Sean Kane: So why don't we start with the patient that doesn't get IV thrombolytics, does not get, uh, endovascular treatment. So basically they come in, for whatever reason they're not a candidate for these more, uh, invasive approaches and we're likely going to give them either DAPT or single antiplatelet therapy and then supportive care primarily. These patients' goals are, and I'm not joking, less than 220 over 120 for at least 48 to 72 hours. I feel like we should repeat that. Their blood pressure goal is less than 220 over 120. Dr. Neu, what on earth are we doing with this crazy high blood pressure goal? Dr. Rachel Neu: I know it sounds really high, but it's something that we allow it to happen. You know, if it happens to be that high, we don't do anything to purposely bring it that high, but, you know, um, if it happens to be that high after an acute ischemic stroke or a TIA, for instance, we'll just let it ride high. So this is what we call like a permissive hypertension. Um, and the goal here really is to make sure that we're keeping the blood pressure adequately high to continue to perfuse the penumbra that we talked about. Dr. Sean Kane: And, and the audience might be saying, well, how common is that that someone's going to have a blood pressure of 200 and you just let it ride there? In acute ischemic stroke patients, part of the stroke, uh, pathophysiology and the body's natural response is to get hypertensive very commonly. So this is actually a very common phenotype of patient where they have a stroke and they have a high blood pressure. And then of course you argue, well, was the high blood pressure what gave them the stroke or was the stroke causing the high blood pressure? And sometimes you won't know, but it kind of doesn't matter. At the end of the day, to help with perfusion to that kind of salvageable area of the brain, we're going to allow them to go up to 220 over 120. And then above that, we would give an antihypertensive to bring them down below that threshold. Dr. Khyati Patel: Yeah, I'm actually glad that we are talking about this because I think, um, you know, the blood pressure, when we see a number that high, it's, you know, within us as a pharmacist, we got to do something about it. But in this case, doing something might actually do more harm. Dr. Rachel Neu: Correct. Dr. Khyati Patel: And so now moving on from no candidates to maybe candidates for our, um, thrombolytics or EVT patients, what is the goal before doing the procedures or giving thrombolytics? Dr. Rachel Neu: So if a patient is a candidate for a fibrinolytic agent or the EVT and the thrombolysis, then the goal before the procedure or the medications being given would be 185 over 110. And then once you start the medication or once you start the therapy, for instance, it drops to less than 180 over 105 for at least 24 hours. Dr. Khyati Patel: A tiny difference. Okay. Dr. Sean Kane: And Dr. Neu, I know that you know this because you teach stroke, but it drives students wild that for whatever reason before you get tPA it's the 185, after you give tPA it's 180. They took five millimeters of mercury off the systolic and diastolic threshold. I don't know why, that's probably just how it was studied, but, uh, it's like another number that students have to memorize and just knowing that the numbers are different I think is probably one of the important things to know. Dr. Rachel Neu: No, for real. But at least it's like five standard for your diastolic and systolic. So it's easier to remember that way. Dr. Sean Kane: Yeah. Dr. Khyati Patel: But I agree with all the different scales that we learn in, you know, like a stroke lecture, for instance, this is just one more thing that you have to remember. Yeah. Dr. Rachel Neu: Again, to reiterate, none of these numbers are new. Um, this we're just reiterating it. Um, but what is new then? What did the guidelines came out and say definitely do it or don't do it? Dr. Rachel Neu: Um, intensive blood pressure reduction. So don't, you know, react to that high blood pressure and also don't try to bring it down too quickly, for instance. So we're not looking at, you know, the perfect less than 140 systolic, uh, for a majority of the patients. If anything, that intensive lowering of the blood pressure can actually do more harm and so it's not recommended. [35:00] Dr. Sean Kane: Yeah, so in the literature for IV thrombolytics, there was at least one trial that was done looking at more intensive blood pressure reduction versus not, just letting them run at that 180 threshold. And there was no benefit. So you're giving drugs and not benefiting them in terms of a clinical outcome down the road. And for endovascular therapy, it was actually harmful. So the more aggressive you lower their blood pressure after endovascular thrombectomy, their mortality was higher and their rate of disability was higher. So at the end of the day, we let these patients ride higher than probably what you might feel comfortable with, especially if you don't see a lot of these patients. We don't overtreat that blood pressure in acute ischemic stroke. Dr. Khyati Patel: And then brings us down to the last one, which is the glycemic goal. So again, the goal has been the same, right, in patients who are in the hospital setting. Um, blood glucose goal is 140 to 180. And obviously we want to avoid hypoglycemia, here is defined as blood glucose of less than 60. So again, these things are not different, but what is new, Dr. Neu? Dr. Rachel Neu: Um, really not much is new. So essentially just saying that, you know, don't try to aim for a more strict blood glucose, um, goal. So we're not aiming for like the 80 to 130 that we typically aim in an outpatient setting or in a patient's, you know, like diagnosed with diabetes in general. In an inpatient setting, we're a little bit more lenient and 140 to 180 is our inpatient goal. And this is not just to, you know, for, uh, stroke patients, it's pretty much for everybody. Um, so, you know, like lowering it down, lowering it too much really has no benefit and it really increases the risk of hypoglycemia. And one thing that I always tell my students and residents, for instance, is that I would rather let it ride high rather than, you know, like having a blood glucose that's too low because it is more detrimental, um, having a low blood glucose compared to a higher number. Dr. Khyati Patel: And you're trying to do this with intense insulin therapy that requires more monitoring and this patient, you know, is already requiring so much monitoring. So if those interventions are not yielding any benefit, then why, you know, overwhelm the staff as well as the patient itself. So. Dr. Sean Kane: One thing I really love about the last two topics that we talked about is almost like a personal mantra that I have, which is like less is more, right? Like less aggressive treatment of their blood pressure or their blood glucose is actually more in the sense that you're less likely to cause harm, less likely to have drug interactions, less likely to have an issue because you're overtreating that blood pressure or that glucose. Obviously they're within some range. So if their glucose is 200, you should still treat that, right? But we're not being uber aggressive and trying to get like the perfect blood pressure, the perfect glucose because these patients are very fragile and it's easy to overdo it with our drug therapy to reduce their blood pressure too much. It's easy to cause hypoglycemia. Uh, so less is more for these patients with respect to those two categories. Dr. Khyati Patel: Right. And once they are stable and discharged and they go home, obviously these factors are going to be something that you need to keep at goal to make sure they don't have a recurrent stroke, right? Absolutely. So, yeah, worry about it then, but while they're in the hospital, less is more. Dr. Sean Kane: So Dr. Neu, we've covered, uh, kind of the newest updates or the most clinically relevant updates at least according to us from the 2026 acute ischemic stroke guidelines. What's one of your big takeaway points from the new update? Dr. Rachel Neu: The biggest one would be tenecteplase. So we're now celebrating tenecteplase as, you know, one medication that's equally preferred to alteplase. Uh, no longer off-label use. Um, and tenecteplase actually have several advantages related to the administration and the risk of medication errors. Dr. Khyati Patel: And I think what also is interesting is the, uh, amount of time allocated, um, that patients can qualify for the IV thrombolysis either using tenecteplase or alteplase. That window in those selected patient is now nine hours as opposed to that 4.5 hours. Dr. Sean Kane: And then my take home point is, uh, the use of IV thrombolytics, who shouldn't get it. So those mild non-disabling strokes. And again, the guideline update was being more definitive in terms of what non-disabling means. We're not going to give thrombolytics if a patient has that low NIH stroke score number and the, the type of neurologic deficit that they have is not going to impair daily activities or their ability to return to work. If they have a low number but it's a highly disabling stroke based on aphasia as we mentioned, then they should get thrombolytics. Dr. Khyati Patel: Agreed. And the last point that I want to talk about is pretty much the use of dual antiplatelet. And so this is only for patients with non-cardioembolic stroke or TIA. So essentially we're pretty much expanding it to also include patients with NIHSS score of four or five. And that it can actually be started up to 72 hours if the patient is eligible for it. Dr. Sean Kane: Wonderful. So as we mentioned, the full guideline is available on our website, helixtalk.com. Again, this is episode 196, uh, for anyone who wants to go through the 100 plus pages of the guideline. And Dr. Neu, I just wanted to thank you for your time and sharing your expertise here. Dr. Rachel Neu: It's my great pleasure to be here. Thank you both for inviting me. Dr. Khyati Patel: Thank you, Dr. Neu. It's been great. Dr. Sean Kane: And then for the audience, we love the five-star reviews in iTunes or Spotify or however you listen to us. And we also have a mailing list that you can subscribe to. So if you go to helixtalk.com, we have a mailing list link that you're welcome to join. You'll get an email whenever new episodes are released. So with that, I'm Dr. Kane. Dr. Khyati Patel: And I'm Dr. Patel. And as always, study hard. [37:48] Speaker 1: If you enjoyed the show, please help us climb the iTunes rankings for medical podcasts by giving us a five-star review in the iTunes store. Search for HelixTalk and place your review there. To suggest an episode or contact us, we're online at helixtalk.com. Thank you for listening to this episode of HelixTalk. This is an educational production, copyright Rosalind Franklin University of Medicine and Science.