SCCM Resource Library-Advances in Stroke Reperfusion Therapy: A Moving Target

Video Transcription

Today, I'm going to be focusing on the second objective, which is recognize new thrombolytic therapies for the management of stroke. And we're going to identify currently approved  thrombolytic therapies for the treatment of acute ischemic stroke. We're going to evaluate the most recent supporting evidence for these therapies and also determine the role  of these therapies based on MRI results or in combination with mechanical thrombectomy in these stroke patients.  As we all know, thrombolytics are often called TPA, which is tissue plasminogen activator. And how this works is tissue TPA binds to PI-1, which is plasminogen activator inhibitor,  and also to plasminogen causing the breakdown of fibrin  as it activates plasminogen to plasmin. And so the two drugs that we currently are using as thrombolytic agents in the US are alteplase,  which is FDA approved for acute ischemic stroke, and tenecteplase, which is off-label currently for acute ischemic stroke.  Some of the differences between these two agents are listed for you here. And tenecteplase is actually a more specific TPA  than alteplase. And I should just say thrombolytic because we'll talk about this in a second, but by using the abbreviations, we can sometimes get confused between these two agents.  So anyway, tenecteplase is more of a recombinant product.  It's an IV bolus versus with alteplase, you have to give a bolus over a minute and then the remaining dose over an hour infusion.  The longer half-life with tenecteplase is about 18 to 20 minutes or so. And the half-life with alteplase is somewhere between four and eight minutes. And with that, with alteplase,  you actually have a greater than 50% increase in about five minutes. And about 80% of the drug is cleared within 10 minutes. But the fibrinolytic activity can last for up to an hour  after the infusion terminates. Now with the longer half-life of tenecteplase, usually we take four to five half-lives to say before the drug is eliminated.  And this does have a biphasic elimination. So the 18 minutes is the alpha phase of elimination  where the terminal phase can go out to about 130 minutes. So you might still have activity with tenecteplase several hours out after administration.  The other differences between tenecteplase and alteplase is that tenecteplase is 14 times more sensitive for fibrin.  And it's about 80 times more resistant towards PI-1. So you have a little bit of difference in the pharmacodynamic action as well. And then the cost of the doses of tenecteplase  using the 0.25 milligram max for tenecteplase is around $3,700 for one dose, whereas alteplase is around $8,800 per dose. And again, based on recommendations from the ISMP,  using TNK for tenecteplase and TPA for alteplase or potentially for all thrombolytics can be really confusing.  And they are recommending against using these abbreviations just so we don't have more medical errors.  Another thing I'd like to mention between these two is tenecteplase is not compatible with dextrose solutions.  And before and after each bolus, we do need to flush the line with saline so that no precipitate occurs.  Now, based on the most recent guidelines for acute ischemic stroke, which came out in 2019, the two drugs are listed in the guidelines,  although we know tenecteplase is not FDA approved currently for stroke. You can see the treatment recommendations here in the level of evidence that is provided. So for alteplase,  we can give it within three hours of symptom onset or four and a half hours of symptom onset based on a few additional criteria. And then also we know that we can do wake up strokes  with greater than four and a half hours from the last known well, but if there is an MRI,  diffusion positive flare negative lesion within four and a half hours of stroke symptom recognition, it still can be used based on, again, some of the newer data.  And then it also can be used for tenecteplase within four and a half hours of symptom onset. And also if the patient is eligible for mechanical thrombectomy,  and you can see the level of evidence for that.  Now, in regards to tenecteplase, it's not widely accepted yet for the diffusion flare mismatch, but it is something that is being looked at and studied,  and we'll touch on that just a little bit more in a few minutes.  So let's look at the tenecteplase trials that are currently out there. We have three, NORTEST, EXTEND-IA, TNK, and the part two of that study that was just published in 2020.  So as you remember, NORTEST was published in 2017. It had almost 700 patients. It was a randomized trial within four and a half hours of symptom onset,  or within four and a half hours of awakening with symptoms with mismatch. Now, the patients in the study had more of a moderate to mild stroke  with a median NIH stroke scale score of four. And they looked at tenecteplase at 0.4 milligrams per kilo dose with a maximum of 40, or alteplase at the 0.9 milligram per kilo dose  with a maximum of 90.  What they found was there were no differences between these two agents in regards to the outcome measures for the modified Rankin scale of zero to one at three months,  and there was also no difference in the symptomatic intracerebral hemorrhages that occurred post-dose. Now, and in addition, they looked at the ordinal shift between the scales  and didn't see any difference in this study. So they followed that up with the EXTEND-IA TNK trial in large vessel occlusions, and they looked at patients who needed thrombolytics  and presenting within four and a half hours of symptom onset. Now, these patients had a little bit more severe stroke with the NIH stroke scale score of about 17 as a median,  and they looked at tenecteplase at 0.25 milligrams per kilo, max of 25, or alteplase at a max of 90.  What they found was a significant difference between tenecteplase and alteplase for their primary outcome, which was substantial reperfusion.  There was no difference in the modified Rankin scale of zero to one at 90 days, but there was an adjusted odds ratio of 1.4 in favor of the tenecteplase  with a trend in that direction, but again, non-significant. And then there was no difference in symptomatic intracerebral hemorrhage.  So in part two, they looked at, again, LVO eligibility for thrombolysis and also thrombectomy within four and a half hours. And what they did here was looked at tenecteplase  at two different doses, at the 0.4 milligram per kilo and the 0.25 milligram per kilo, looking at about the same type of patients with that moderate, a median NIH stroke scale score  of 16 to 17, which is in the moderate range for that median. And what they found here was really no difference in substantial reperfusion between the two doses  or in their modified Rankin scale scores. However, there was a trend towards a higher symptomatic intracerebral hemorrhage in the higher dosage strategy.  So if we summarize all these tenecteplase outcomes, based on the type of trials that were done, either comparison with alteplase or the other tenecteplase dose,  you can see that, again, in the more mild strokes, there was no difference between tenecteplase  and alteplase in regards to outcomes. And with the more moderate to severe probably patients, as you look at those, there might've been a slight trend  in a more effective treatment strategy with tenecteplase, but again, no differences in the symptomatic ICH seen with these studies.  So in summary for tenecteplase, it's a cheaper agent. It's more convenient in administration. We know it's at least as effective as alteplase and has similar safety profile.  And it potentially has some theoretical benefits in regards to giving it quicker in our patients. And then further studies are still pending for this drug.  So I would tell you to be aware of this and make sure you're looking for some of these studies. These are some that are currently ongoing. Tempo 2 is looking at tenecteplase  versus the standard of care in minor stroke or TIA within 12 hours of onset. The TASTI trial is tenecteplase versus alteplase in a mobile stroke unit.  And a test 2, looking at those two agents in non-endovascular patients. And then finally, the TWIST study was just looking at wake-up stroke  within four and a half hours of symptom onset. And that's tenecteplase versus placebo. So be on the lookout for those studies.  Now, looking at DWI flare mismatch trials for these agents, we know that we've had a couple over the last several years that have really helped guide our therapy.  You have MR-WITNESS, wake-up, THAWS, EXTEND-IA, a subgroup analysis, and then the TWIST subgroup analysis. And again, that is ongoing.  So in MR-WITNESS, this was a single-arm open-label phase 2a study looking at treatment with alteplase within four and a half to 24 hours of last known well.  So again, it's not within our standard three to four and a half hours post-symptom onset. These patients had an unknown time of onset, and it turns out that last known well,  the median for this group was around 11 hours. They used the DWI flare mismatch in order to enroll these patients, and they had a sort of moderate NIH median score  of about six and a half. And then the average symptom discovery till dose of alteplase in these patients was about three and a half hours.  And what they found at the modified Rankin scale score for good outcomes was about a 39% compared to about 52%, which is what we found for ECAS, which was the three to the four  and a half hour window for alteplase. So similar there, as well as similarities in regards to low rates of symptomatic hemorrhage. And the overall similar results  that we saw in the ECAS trial, so the authors of this study concluded that it was safe to give alteplase to these patients with a mismatch. Then we had the landmark wake-up trial  that came out in 2018 that, again, last known well, greater than four and a half hours with a median of about 10 hours. And this was, again, based on DWI flare mismatch  and then excluded patients that were undergoing mechanical thrombectomy. Again, NIH Stroke Scale score of around six for median, and this was looking at alteplase versus placebo  with about a three-hour median onset symptom recognition to dose.  And the primary outcomes here were significant in favor of alteplase over placebo, as you can see here with both the MRS of zero to one at 90 days.  The median MRS at 90 days was also better in the alteplase group.  And symptomatic ICH, again, was a little bit higher percentage in alteplase, but similar in regards to statistical analysis for that.  So in regards to the THAWS trial in 2020, looking at patients who were eligible to receive alteplase, again, mismatch, and these excluded mild patients  and also the severe stroke patients. And this looked at a smaller dose of alteplase, a 0.6 milligrams per kilo versus standard of care.  Primary outcomes here were no different, and it was actually terminated early due to the positive results of the wake-up trial.  So there was also a NORTES subgroup that looked at the higher dose of tenecteplase versus alteplase and looked at the FLIR mismatch. And in this group, again,  no difference between outcomes between the two groups and maybe a shift in four points or more that was significant in the NIH Stroke Scale score in favor of tenecteplase,  but no difference in symptomatic ICH.  So when it comes to the mismatch outcomes, you can see here the modified Rankin Scale scores of zero to one at 90 days, you can see are very comparable between the groups here  with very similar symptomatic ICH side effects.  So in the mismatch summary, the ability to identify patients who benefit from thrombolysis with MRI is known now,  and equivalent safety outcomes, it looks like between the two agents. However, further studies are needed, including with tenecteplase in regards to the mismatch.  And finally, in combination with mechanical thrombectomy trials, the DIRECT trial was a Chinese trial that just came out in 2020, and it looked at acute ischemic stroke  and large vessel occlusion  in patients who could receive alteplase within four and a half hours of symptom onset. And these were more severe, moderate to severe strokes of NIH Stroke Scale score of 17.  And it looked at mechanical thrombectomy versus alteplase plus mechanical thrombectomy. And what they found in this study was a non-inferiority  of the mechanical thrombectomy alone compared to alteplase. However, there was a trend towards a decrease in perfusion prior to mechanical thrombectomy  and the overall success of the reperfusion in the mechanical thrombectomy group alone. And as you can see, there was also a higher percentage of symptomatic ICH.  So for this study, the conclusions were that the primary outcome was just above the pre-specified non-inferiority margin. And so you cannot rule out the benefit of alteplase  in combination with mechanical thrombectomy at this time.  The alteplase did delay groin puncture by about five minutes. And it does not apply, this study did not look at administering alteplase at one institution and then transferring  to another institution for thrombectomy. So that's gonna be, has to be a new study done. And also notice that this study was done in China, which has different treatment strategies  than we do in the U.S. And that also should be taken into consideration.  So in summary, the data support tenecteplase and alteplase as safe and effective thrombolytic options for the treatment of acute ischemic stroke.  Currently, however, alteplase is the only agent that is FDA approved for this indication. The major differences between these two agents is the dosing strategy,  the kinetic characteristics and costs. And then with the DWI flare mismatch, we can identify patients who may benefit from alteplase in patients  with symptom onset of greater than four and a half hours. However, again, we need more studies for tenecteplase in this situation.  And then from the latest study, mechanical thrombectomy plus alteplase is currently the standard of care for acute ischemic stroke treatment in eligible patients.  However, newer data may suggest that mechanical thrombectomy may be non-inferior to the combination therapy.  And finally, I would like to acknowledge two of my Neurocritical Care Research Fellows, Melissa Sandler and Sulabhan Al-Mohaish, who have helped me put this presentation together.  Thank you very much. Hi there, I'm Greg Albers, Professor of Neurology and Director of the Stroke Center at Stanford University. And I really appreciate the opportunity  to provide an update on endovascular therapy for the Society of Critical Care Medicine's 50th Congress. My disclosures are shown here.  So in 2021, we now have a transparent time window, which means that imaging can provide us with information about whether the patient has salvageable tissue or not  when they present with a stroke. And because of this, stroke is now much more treatable than previously believed, and the door is open to treat many more patients  and design trials that are not restricted to arbitrary time windows.  So let's dive into an update on endovascular therapy. So in 2015, five trials were published in the New England Journal that completely changed the landscape  for how large vessel occlusion stroke patients would be treated. These trials that were performed all over the world compared stent retriever therapy with IV thrombolysis  to IV thrombolysis alone. The yellow bars show the good outcome rate in the control group, which was the IV thrombolysis. The blue bars shows how much additional benefit  you could see by adding in the stent retriever. And you can see that the trials differed in the good outcome rates for both the control and the endovascular group.  And they really depended on how carefully selected the patients were, how much effort there was to identify patients who had salvageable tissue.  But regardless of the method chosen to select the patients, all of the trials were positive, which made a easy guideline change for the American Heart Association in 2015,  when they came out with a class one level A guideline, meaning a new standard of care that patients with large vessel occlusion of the proximal MCA or ICA should be treated with  endovascular therapy if they had certain criteria. And if you look at the criteria, you can see the  number six appearing frequently. They had to be within six hours of symptom onset, they had to  have an NIH score of six or more, and they had to have a small ischemic core designated by an  aspect score of six or greater. So this was a major advance, but it didn't solve the problem for the vast majority of patients who had large vessel occlusions across the country,  because up to a third of patients wake up with their large vessel occlusion, and up to another third have their occlusion far away from a comprehensive stroke center.  So that means that most patients couldn't make it in with this tight six-hour time window,  so the question was what could be done to shatter the stroke stopwatch and be able to treat the  majority of patients with large vessel occlusions. So to do that, we needed late window trials, and  this was the DAWN and Diffuse 3 trials that were published in 2018, and here all of the patients  were selected with advanced imaging, which would allow you to identify patients with salvageable  tissue and not enroll patients who had had a completed infarct. And as you have likely heard, these trials were extremely positive, showing major benefits of endovascular therapy,  and what these trials were able to do was to shatter the time window and break away from the  treatment effect modification by time that we have seen in virtually all of other trials. So  if you take a look here, this was Mr. Clean. This was one of those six-hour treatment trials. What we  can see is the absolute risk difference. In other words, the benefit of treatment is declining over  time, and as you get out to eight hours, it goes down to zero. So the treatment effect is  gone by eight hours. This is a curve that we have seen over and over again in trials that did not  select patients based on advanced imaging. However, when you look at the trials that used advanced  imaging, such as DON and Diffuse 3, what we can see is that the good outcome rate in the  endovascular arm stays relatively constant over time, where if anything, the good outcome rate in  the control group drops over time, which means that the treatment effect remains stable. There  was no hint of this declining treatment effect over time. If anything, the trend was the opposite  because the control group was doing so poorly in the late window. If you come in at 14 or 16 hours  with an occlusion, it's very unlikely that you're going to have spontaneous recantalization lead to  a benefit. So these patients did very, very poorly. That meant that the treatment effect, if anything,  was trending upward over time. So what we can summarize here is that the treatment effect is not modified by time in these late window trials, and that led to these guidelines that  came out in 2018, which are still in place today, indicating that we now have level 1A treatment  guidelines for late window patients. And all the way up to 24 hours in the DON trial were  patients shown to have substantial benefit to thrombectomy. So the recommendation here is that  because these trials relied on advanced imaging for patient selection, that this advanced imaging  should be carried forward into clinical practice when patients are selected for late window  thrombectomy. So on the same day that we presented the Diffuse-3 data and that these guidelines came  out, we also published this paper called the Late Window Paradox to try to explore this paradox  between why the treatment effect is actually larger in the late window trials than it was in  the early window six-hour trials. So here with the Hermes pooled analysis, we can see the good  outcome rate in blue in the endovascular arm versus in yellow, the control arm that got IV  thrombolysis. Here in the late window trials, you can see that control arm, which in general did not  get IV thrombolysis because they came in too late, was much lower. And that's part of the  reason for this larger treatment effect. But the other explanation is what we alluded to earlier,  which is the advanced imaging allows you to identify patients who have slow growth rates.  And by increasing, including these patients with slow growth rates because of good collaterals,  that means large penumbral volumes to reperfuse. So this is a slide from many years ago from the  Diffuse-2 study that looked at how rapidly does the ischemic core volume grow over time in patients with MCA occlusions. And what we found is that it was actually a big surprise  that 50% of patients with MCA occlusions had very slow growth of the infarct core, and only about 20% of patients had the rapid growth that we were taught about in medical  school. So really, strokes grow much slower than had been thought, and that means that we have a  lot of opportunity if we focus on these patients with slow growth in the late time window. And this  actually provides an explanation for why we saw the more favorable results in the trials like  EXTEND-IA and SWIFT-PRIME in the early window when they focused on identifying patients with  penumbral tissue versus studies like Mr. Clean and Thrace that didn't look for penumbral tissue,  and as you can imagine, would have had about 20% of their patients having a completed infarct. So we have more data that just came hot off the press. December of 2020, we saw the  FRAME trial get published in Stroke. This is a trial that looked at early window thrombectomy,  and it included patients both with mismatch and with no mismatch. The no mismatch patients are  those who have evidence of a completed infarction. This was primarily based on MRI diffusion and  perfusion imaging. So what you can see here are the patients who have a mismatch, and you can  look at how well they did if they had successful reperfusion, which was quite well, and much better  than they did if they had no successful reperfusion. So you can see this strong association between  reperfusion and good outcome. What about the 15% of patients in this study who had a completed stroke  and still went on to thrombectomy? Well, what you can see is that the good outcome rate in the  reperfused patients with a completed stroke was actually less than in the patients who did not  have successful reperfusion. So failure to reperfused was associated with better outcomes.  And if you look at the odds ratios for treatment effect, you can see that there was a significant  difference indicating that this mismatch selection has a significant influence on the response to  endovascular reperfusion. So it again goes to help understand why we would see smaller treatment  effects in trials that didn't use penumbral imaging than those who did in the early window,  and that why trials that go into the late window and identify only patients with slow core growth  and salvageable tissue are going to have large treatment effects despite the late time. This principle holds not only for endovascular therapy, it also holds for IV thrombolysis.  This is the historical attempts to break the four and a half hour window for IV tPA therapy,  12 trials, all unsuccessful, but once trials were done that took into account salvageable tissue,  then the situation changed. You're probably familiar with the wake-up trial that used a  flare diffusion mismatch to identify patients who were in the early window despite waking up,  but the first trial to actually treat documented late window patients beyond four and a half  hours with IV thrombolysis was the EXTEND trial. This used the same imaging techniques that were  used in SWIFT-PRIME, EXTEND-IA, DIFFUSE-3, and DON using perfusion-based imaging to identify  those patients who had a mismatch, and this was a successful trial. Even more impressive was this  pooled analysis that came out in the journal Lancet right after the publication of the EXTEND  trial showing that if you take two other late window IV tPA trials and you divide the patients  into those who have a mismatch versus those who don't, you can see the exact same effect that I  just showed you in the FRAME trial. If you have a mismatch, there's a nice benefit from tPA versus  placebo. If you don't have a mismatch, if you have a completed infarct, which was the case for the  vast majority of these patients, no mismatch, then you see the opposite effect. You see no benefit,  in fact, a trend towards worse outcomes in the tPA arm, many more deaths and twice as many patients  with a Rankin-5 than in the placebo group. So it's this mixture of a larger group that benefits  with a smaller group that has harm that can lead to a neutral trial, but by excluding these patients  with the unfavorable profiles, then you can get a positive IV trial all the way out to nine hours.  We've already started using IV tPA using the EXTEND criteria at Stanford. This has not been  assessed by the HA guidelines yet, but expect over the next few years to see more use of late  window IV thrombolysis based on imaging. Okay, well, the news was not all good over the last  few years for endovascular therapy. In 2020, we had the results of the BASICS trial, and just  before that, we had the results of the BEST trial, which were basilar artery occlusion randomized  trials, neither of which failed to establish benefit for basilar thrombectomy. Now, there are  a wide number of reasons that people have discussed why these trials may have been negative, and certainly I suspect virtually everybody in the audience believes that basilar artery  thrombectomy can have amazing positive effects if you get the right patients, but the question  has been how do we select the right patients? A traditional mismatch doesn't work in the posterior  circulation, because you can have a relatively small core, but all sorts of critical brain areas  dead, such as the midbrain, the pons, the thalamus, etc. So, a new approach that's being looked at by  a group called the Posterior Circulation Study Group is saying let's look at areas with very  severe perfusion delays in critical brain areas, and what's been seen in the preliminary data is that if you have multiple critical brain areas, such as bilateral cerebellum, pons,  midbrain, thalamus, have severe perfusion delays that these patients don't appear to respond to  endovascular thrombectomy of the basilar artery, where patients with more favorable perfusion  patterns have a fantastic response, and this is going to be followed up by an NIH grant that we're  coordinating out of Stanford that will start this spring. So, let me finish up in my last  six minutes here with some unanswered questions regarding endovascular therapy. So, one of the  issues is do we absolutely need the perfusion imaging for late window thrombectomy, and the  main trial that's looking at this is the MR-CLEAN late trial, and here what they're doing is trying  to see whether good collaterals on a CTA could substitute for favorable perfusion imaging in a  large trial that should finish within the next year or two. The difficult part is that if the  site has perfusion imaging, it really would be unethical to randomize somebody who had a diffuse  3 or DON type favorable profile to a control group that doesn't get thrombectomy. So, for patients  who have a favorable perfusion imaging profile, they're not included, but if the site doesn't do  perfusion imaging, then patients can be randomized if they've got moderate to good collaterals on CTA.  Okay, what about busting through the 24-hour treatment window? Any time window is arbitrary.  How many patients still have salvageable tissue between 24 hours? Well, we looked at this in the  Diffuse 3 trial, specifically at the control group, and we found that imaging performed at 37 hours in the control group identified 20% who still have the target mismatch profile.  Here's an example of such a patient, 73-year-old woman. She's got a wake-up stroke. She comes in and has a very favorable profile. You know she's got good collaterals based on the  fact that there's a small core, diffusion lesion only 5. The perfusion lesion for her MCA occlusion  is quite small at only 41 ml. Typically, you see at least 100 ml, often 150 for an MCA occlusion,  but hers is small and has lots of holes because she's got good collaterals. She's randomized to  the control group. Her MCA remains occluded, and 24 hours later, now about 37 hours after she was  last known well, we can see that the perfusion lesion has grown. So, if we remember before, it  was at 40 ml with lots of holes, and look at it now. It's up to close to 75-77 ml with many fewer  holes. So, this is watching collaterals fail over time. The infarct is growing, but it is not yet  caught up to its full size. The full size will come later, and as we look a couple of days later,  we can see now we've reached a 70 ml infarct. The patient is eventually reperfused, but not before  she grew into that large penumbra. This has been taken one step further by Dr. Kim's group in South  Korea, where they have treated a select group of patients, a median of 44 hours after last known  well. These are patients who had favorable imaging profiles, and what they found is in this case  control design, not randomized, but there was a substantial apparent benefit from endovascular  therapy. These patients who had the therapy did much better than the controls, and in particular,  what they could see is that patients who met the imaging criteria for the DIFUSE-3 trial with a  substantial penumbra had a very dramatic benefit. So, this may be a way to start treating later  window patients. It'd be nice to have a randomized trial, but in the absence of that, we have been  treating patients beyond 24 hours at Stanford if they have the favorable profile. What about  this hot topic of treating large core? DIFUSE-3 cut off the core at 70 ml. That was the same with  EXTEND-IA in the early time window. Can we treat patients with a core more than 70? I suspect the  answer is yes, and I think we're going to see some positive results over the next couple years from  these large core trials, which are going on both in the early and late window. These trials either  focus on a low aspects for enrollment or they focus on perfusion imaging, and I'll make a little  bit of a plea for why I think perfusion imaging is the way to go if you want to look at large core.  For one, this is a type of patient where if you use the early window aspects rule of six or more,  you would not treat this patient because the aspects score is five, but if you look at the perfusion imaging, they're picking up the aspects points from small volume deep regions  where there's a substantial benefit in reperfusion if you see this huge penumbra. The other thing  about aspects is the iterator agreement is not terrific, so if you erroneously called this  patient a three by over calling these two, then clearly this patient who should be treated wouldn't.  The other issue is that sometimes in the early window, the aspects hasn't had time to show how  much damage is there, so here we can see somebody who has got substantial evidence of low CBF,  a core estimate of 160 three hours after symptom onset, but the aspects is good, so everybody's  going to treat this patient, but in the Select-2 trial, this patient would be randomized, so we  could try to figure out whether somebody with a core of 160 would benefit. Why would we think  they would benefit? Well, they still have a large mismatch. You can see a mismatch volume in the range  of 150 mls, but why would we think they wouldn't? This core, as you get beyond, you know, 90 minutes  or so, anything with a CBF that's reduced by 70 percent or more, which is going to show up pink  on this map, we have seen is almost never going to be reversible, and the key areas of important  language and motor function look like they've got irreversible injury, so an unanswered question,  how big can the core go? So, it is really an exciting time for endovascular therapy. We are going to move on over the next couple years to answer some of these unanswered questions,  including the role of pediatric endovascular therapy, but you can see that there is a huge  benefit that has been seen by the trials that I've reviewed over the last few years. We now know  that time is obviously very important, but that we should not use time as a reason to exclude  patients from treatment. Even if they come in late, we should evaluate whether they have salvageable  tissue, and if they do, we should either reperfuse them or get them into a study where we can try to further advance the field. Thank you very much.

Video Summary

This video provides an update on the use of thrombolytic therapies for the management of stroke. The speaker discusses the currently approved thrombolytic therapies, including alteplase and tenecteplase, and highlights their differences in terms of dosing strategy, kinetic characteristics, and cost. The speaker also emphasizes the importance of advanced imaging techniques such as MRI and perfusion imaging in selecting patients for thrombolytic therapy. The use of advanced imaging allows for the identification of patients with salvageable tissue and helps guide treatment decisions beyond the traditional time window. The speaker reviews the results of various trials, including EXTEND-IA, SWIFT-PRIME, DIFFUSE-3, and DON, which have shown the benefits of endovascular therapy in both the early and late time windows. The speaker also discusses the challenges and unanswered questions in the field, such as the selection of patients for basilar artery occlusion and the treatment of patients with large core infarcts. Overall, the video highlights the significant advances and potential of thrombolytic therapies in stroke management, and emphasizes the need for further research and clinical studies in this area.

Asset Subtitle

Neuroscience, Procedures, 2021

Asset Caption

The Society of Critical Care Medicine's Critical Care Congress features internationally renowned faculty and content sessions highlighting the most up-to-date, evidence-based developments in critical care medicine. This is a presentation from the 2021 Critical Care Congress held virtually from January 31-February 12, 2021.

Learning Objectives

Recognize new thrombolytic therapies in the management of stroke
Assess new mechanical thrombolytic therapies in the management of stroke

Advances in Thrombolytic Therapy
Gretchen M. Brophy

Mechanical Thrombectomy
Gregory W. Albers

Meta Tag

Content Type Presentation

Knowledge Area Neuroscience

Knowledge Area Procedures

Knowledge Level Advanced

Membership Level Select

Tag Stroke

Tag Neuroimaging

Tag Cerebral Blood Flow

Year 2021

Keywords

thrombolytic therapies

stroke management

alteplase

tenecteplase

advanced imaging techniques

endovascular therapy

patient selection

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