We, you know, we're really proud of all of this investment in evidence. Again, there's not a lot of spaces outside of well-developed areas like coronary intervention that has invested in an evidence-based like this in the post-market space, so quite an impressive opportunity to change how we take care of patients for the long term, change our guidelines, support reimbursement, a lot of important stuff comes from level one evidence like this. We're getting close to the end of the session, but we have time for Q&A. I'm going to hand it back to Rob, who does a better job than anyone at managing question and answer sessions. We have a few in the chat, and I want to encourage anybody else who remains on the line to please put questions in there for us to discuss. Rob, all yours. Thanks, Eric. So I'll, you know, get this started, and again, I want to thank everybody for showing up tonight for the panel, everybody for logging in. We just went through, you know, four pivotal randomized trials evaluating intermediate risk patients versus anticoagulation alone, and Aki, I'm going to ask you as, you know, one of the, you know, lead principal investigators of these trials and leading the only, you know, NIH-funded trial, to everybody watching at home, you know, how important is it to evaluate patients to, you know, be enrolled in these randomized trials, and how, you know, critical is it going to be for our future endeavors moving forward? Obviously, Peerless One was a great effort, and again, I want to congratulate the investigators with Sam, Corinne, for, you know, leading that effort, but I think the work at hand are these four randomized trials versus anticoagulation that hopefully will allow us to really have level one evidence and decide the, you know, the care that we're going to provide moving forward, perhaps even change the guideline documents. So, if you can just give your own perspective on how important it is right now to enroll in these four randomized trials. Overall, I would say that physicians are often surprised at how their perceptions don't always match up with the clinical trial results, and what I would argue is that even those that we've convinced ourselves need catheter-directed therapy, if they're included in a trial, it's for a reason. You know, I think the people that have designed these trials have looked very carefully at these patients and have really chewed on equipoise and said that this population needs to be studied. So, if you have a portion of that population that just doesn't enter the trial because of inherent bias at a clinical trial site, that really does a disservice to the overall field because, you know, if you assume that you know that a patient is going to deteriorate as an example and therefore don't put them in that trial, it's really, you know, potentially hurting the field, and I think all of these trials, what we should acknowledge, have a bailout potential for those patients. None of these trials are allowed to interfere with clinical care, so the threshold may be different than at an individual site, but ultimately the ability for us to really involve the entire, say, spectrum of intermediate-risk PE in these trials is what's going to determine whether, you know, the trial results are going to be able to drive our practices or whether we're going to still be left in the dark and still be asking questions, is that the same population that I'm treating now? And so, that's where the importance of randomized trials and sticking to eligibility criteria comes in. I just want to make a quick comment, Rob. You know, I just want to remind everyone that less than 20% of hospitals in the U.S. are performing the majority of PE interventions. In Europe, in Asia, in Australia, are incredibly far behind us. Catheter-based interventions is not the norm outside of many of our centers. And so, just reminding that although a lot of us feel like we have a decision made on catheter-based intervention, that's not how most PEs are managed across the country, as well as across the world. And so, as much as we think we're on top of something and are ready to put our flag down, I think that it's important that these trials really reinforce what we think we're doing is correct for our patients. Excellent comments. I'm going to go rapid fire with questions from the audience to people that are on the panel. Jay, I'm going to you. How do you explain the similar bleeding rates between large-bore aspiration thrombectomy and CDT in PIRILIS-1? I would explain it in two ways. Number one, it's a low-bleeding-risk population, extraordinarily low-bleeding risk. So, they were at lower risk of bleeding from any interventional therapy. And then, I would explain that as number two is it doesn't look like interventions are causing a lot of bleeding. So, I think that's a happy thought for all of us who do these procedures. So, I think those are simple ones. Fabulous. June, there's a question about anesthesia. And I'll ask you, you know, pretty simplistically, for large-bore aspiration, anesthesia always, sometimes, never? And then, similarly, for CDT, do you use anesthesia always, sometimes, or never? So, practicing in the cath lab, I don't use anesthesia. I avoid them like the plague, if I can. Generally, I actually warn the patient up front for anyone coming into the lab with PE. I don't plan on using a lot of anesthesia. If anything, I give a very gentle 25 mics of fentanyl, and that's it in the beginning. If I'm doing a thrombectomy, as I see that the blood pressure is getting better, heart rate is getting better, I might sneak in a touch of Versed towards the end, just for my figure of eight closure. But, in general, I avoid anesthesia. Julie, did you have a comment on that? Yeah, just the comparison between cath labs that are perhaps used to sicker patients and STEMIs, their nursing group may have different training than perhaps other labs. And so, that also plays a role. Some centers just have anesthesia, if they reach certain thresholds of oxygen requirement, for example. But, even with anesthesia there, in my lab, it is local only. They are there in case of a deterioration only. Julie, I'm going to ask you the next question, which is a comment from Keith Pereira, which is, how do you explain that the functional improvement that was seen differently between the two groups at 24 hours equilibrated at the 30-day follow-up? Obviously, this is not the first trial to see this. There have been other trials, Canary being just another great, great example of that. But, if you could just explain that to the people logging in. Yeah, I think it's happening. It's something that I wish we talked about a little bit more, because it shows that we might be speeding things along. But, at 30 days, people are evening out. I mean, anticoagulation does work. It's doing something in the background. And so, though we might be getting people out of the hospital sooner, at 30 days, pretty equal. I'm curious what Aki has to say about it, too. Yeah, thanks. I'll try to be quick. I just want us to be very careful about our interpretation of the secondary outcomes. This was an unblinded study. I did not see any evidence of core lab adjudication and independent, unbiased adjudication. I don't know how somebody determines respiratory rate and who is doing that. And certainly, those people that are doing it are unlikely to be blinded. So, please, as a group, we need to really look at the methodology for all of the secondary outcomes and make sure that we draw the appropriate conclusions. Thanks, Aki. Very well said. And, Jay, I'm going to go to you with this next question. We got two more, then we're going to wrap it up. What percentage of your high risk or intermediate high, or however we're grading them these days, end up on mechanical circulatory support, and how do you decide? Intermediate high risk patients, it would be, it's quite unusual for them to end up on MCS. That would be patients at the very top end of the scale. And then, oftentimes, it's when we're starting a procedure, they're continuing to decompensate a little bit more, and we think it's, and we're actually starting a presser. So, they're making the transition from the intermediate group into the truly high risk group, presser starting, and we think we're going to be safer to perform a procedure with MCS. The second comment is just for Aki's point is, there is core lab adjudication in peerless, but regarding the imaging studies. And so, there was a core lab for that. That was an independent core lab. Regarding the clinical endpoints, it was an independent CEC that evaluated them. So, that's for adverse events. And then, finally, for the functional endpoints that you mentioned, like giving the scale of NYHA, there was, you know, stereotypical kind of documents that were given, but those were obviously just obtained by a research coordinator and then submitted to the trial central steering committee. So, just so everybody knows what the details were along the different types of secondary endpoints and how they were adjudicated. Thanks, Jay, for adding that. Eric, I'm going to close it out with you, because I can't think of anybody better to answer this. And the question is, how do we move past this era that CDT is bad for this patient because they've got a saddle, or large-bore thrombectomy is bad for this patient because it's all segmental PE? And how do we actually come up with a clinical algorithm of which device to use when? Yeah, great question. Thank you, Sami Seifo. And, you know, this is where we need to be. This is, again, a toolkit. There is no one right tool for any patient. So, as you get comfortable, I think some of this is going to be determined at the site level, what your expertise is, what you feel comfortable using when there is equipoise across patients. But some of it, I think, will shake out as we get more data and understand a little bit more on when to use these right tools. And I think there are some clear examples as we do more clot-in-transit, higher thrombus burden that we might be favoring thrombectomy. When we have that more distal clot, we might be favoring ECOS or more chronic clot. And these algorithms might be developed in different ways across the country, but are important to really harmonize the idea that this is a group of devices that can be used to treat our patients. Patients are the focus here, and we have to match our operators with our patients as well. Aki, you've got your hand raised. Go ahead. We're not yet at the stage where we can go to algorithms. We are not there yet. We still need to figure out if we're doing the right things for most patients, and then algorithms can follow. So I would argue that we're still not there. Which is why we need to enroll in all these randomized trials versus anti-coagulation alone. So thank you for that. We're a couple of minutes past the hour, but sincerely, I want to thank just such wonderful faculty panel tonight, such incredible expertise and insight. I enjoyed the conversation. I learned a lot. I hope all of you did. I want to thank everybody for logging in tonight, and I hope you found this educational and informative. I want to thank Sky and SIR for sponsoring this event and putting it on. I love the collaboration between the two organizations, and I'm looking to more collaboration in the years ahead. I want to thank our corporate partners that helped support this event, and thank you for everybody, including NIH, for funding these incredibly important randomized trials. Everybody, thank you so much. Have a great evening.

evidence-based healthcare

randomized trials

thrombectomy vs CDT

treatment guidelines

clinical algorithms