Hello, everyone. I'll tell you that maybe my presentations are not as cool as Dr. Siddiqui's and Dr. Ananda's. You know, I didn't bring any cool pictures like you did, but we'll see what we can do here. You will hear a few things that they both said that even if you are a proponent of medical management, but I'm not saying that I am, but it's what I'm here to talk to you about, that you're going to hear repeated. And we'll get to it. I really don't have anything else to disclose about this topic in particular, but I guess, you know, that's been the question I've been trying to debate. Do we need to treat a patient who doesn't have any symptoms? And, you know, there's pretty much been over 25 years of data, right? Those are the three main landmark trials that we base all our decisions for asymptomatic carotids, right, in 1993, the Veteran Affairs Study, the Asymptomatic Carotid Atherosclerotic Study, and the surgical trial. And, you know, we've seen all these three trials, and we're still debating what do we need to do. And on these trials, if you add up all those data, you know, properly selected patients, the intervention will result in a reduction of stroke risk of 53 percent with a five-year risk reduction of 6 percent when compared to medical management. And so that sounds great, right? If that is the data that we have for intervention, why are we not intervening on everybody? And the problem that we have is that none of those trials had an adequate management on medical treatment. Even the more recent trials that had some asymptomatic treatment of the carotids, like SAFIRE and CREST, they did not include a dedicated medical management arm. I'm going to move this right here. So the things that have changed, of course, is that we, as we've discussed, our medical management options are much better. And it has been proven effective in other trials or other areas that are similar, like Dr. Siddiqi mentioned, and like the SAMPSIS trial. So in this trial, what we did, we had stenting versus aggressive medical management for symptomatic stenosis of greater than 70 percent in intracranial arteries. And you can see the deviation in the curves there in between the management, the medical management and the surgical management, with a much favorable rate for the medical management. With the data that we had before, we expected that the medical arm would have been pretty much over this high in terms of the risk. But in the medical management in that trial of SAMPSIS, we saw that the results were actually a lot better when we did medical management. It's important to note that the medical management in this particular trial was very different than any of the trials that we had done before for any sort of stroke patients. Some people like me like to say that we're not really real life, but that's up for debate. Maybe that's what we need to make real life be. And so that puts us like, how are we going to answer the question? We have all this data that doesn't compare medical management. We have all these trials that say that medical management might be better than we thought before. So multiple trials have been trying to run and evaluate these patients with asymptomatic carotids. The space to trial, I'll show you some of their data in a second, but it was best medical therapy versus best medical therapy and stenting versus best medical therapy and CA. The ECST2, best medical therapy versus immediate revascularization versus delayed revascularization, although it includes both symptomatic and asymptomatic carotids, and the CREST2 trial, which I'll talk a little bit more detail in a second. So the space to trial was stopped early. They only had 513 patients randomized, and they stopped because they had slow recruitment. And one of the things that they cite for the slow recruitment was that a lot of the patients that were referred with carotid stenosis, they were expecting already when they went to the proceduralist that they were going to have some sort of intervention to fix the carotids, and that medical management wasn't good enough. But if you see their early results, the 30-day rate of death or stroke, it was really low with endarterectomy and carotid artery stenting, but it was zero with best medical treatment. And so as we have mentioned here before, then CREST2 is hopefully one of the landmark trials that helps us guide what are we going to do with these patients. They include patients with greater than 70% asymptomatic stenosis, and they will do their medical management versus CEA, medical management versus CATS, with an endpoint of stroke or death at 44 days. This is kind of like the study concept. Again, it will be the endpoints, CATS versus medical management, CEA versus medical management. And like Dr. Siddiqui mentioned before, the study protocol is allowing for procedural latitude for surgeons to choose the type of surgery that they feel more comfortable with, and the endovascular areas to also use the different types of devices that are going to be available and that will become available as the trial is underway. And this is then that medical management. So for the endarterectomy side, patients are going to be treated with aspirin, 325 milligrams daily. And for the stenting trial, they're going to do dual antiplatelets for at least one month after the procedure and then aspirin. Both trials will be on statins and if required, PCSK9 inhibitors. And you can see there that they're going to work hard and hitting those primary risk factor targets. Very aggressive blood pressure management, very aggressive lipid control, and even secondary factors like the non-HDL cholesterol, hemoglobin A1C, smoking cessation, weight management, and exercise. Now, in real life, when a physician sees some of these patients, we encourage our patient population to do all these sort of things. And we try to track these sort of things. But in a clinical trial setting, they're going to really focus and emphasize this with the follow-ups and the calls, just like they did in the Sampras trial. And we'll see if that actually makes a difference that it made in the intracranial trials. This is the prevalent for the patients who do not meet the targets with statins. So this will be available for the patient population as well if it's required. And then this trial is going to have a hemodynamics, kind of like an ancillary study to it. This particular branch is of extreme interest to me and I will tell you why in a second. But what they're going to do is going to see if revascularization has an impact on patient cognition. And you can see there, you know, whether they go through surgery or they go through stenting, see if it makes a difference in this patient population. Like Dr. Siddiqui presented some of the data as well. And so because there is this previous data that shows us that there could be some changes in cognition in the patient population with carotid artery disease, whether they have had strokes or not, I think that this trial will, this section of the trial will open up a huge patient population that we haven't had the time to explore before and it can make a big impact. Now, I think that unfortunately the cognition at one year might not necessarily reflect that. But certainly it's a start for this patient population. And some extra thoughts that maybe we didn't ask for. I mean, I think that after all these trials are done, there's still going to be some questions out there. I think that the degree of stenosis is not necessarily the only factor that we need to take into consideration. Not necessarily perhaps for the asymptomatic patients, but for the symptomatic patient population. I'm a firm believer that just because I don't have a 70% stenosis doesn't mean that my stroke wasn't caused by a carotid plaque or an ulceration. And you guys touched on that as well. So I don't think that the percentage of stenosis should be the only thing that guides us whether to treat these patients or not. You need to take into consideration if there's a hemorrhage, if there's an ulcer, if they're regular or irregular, hemogeneous, heterogeneous, regardless of which technique you use to assess your patient. And then, of course, the other item was that the patient population that may be affected by having just excellent flow to their brain with that hemodynamic study will really be important. And lastly, I think that there's a little bit of opportunities out there in research that we haven't quite gotten to involved in yet. And so can we predict the type of patients that will need the interventions? There's a couple of articles out there recently about biomarkers that help guide for plaque instability, micro RNA that has been elevated after the patient has had strokes. Perhaps if we monitor those, we'll be able to see which patients are truly at risk and would truly benefit from an early intervention. And I think that's for you guys. Thank you.

asymptomatic carotid artery disease

stroke risk reduction

medical management

intervention

CREST2 trial