Perfect. So, you know, first and foremost, I think that the investigators for this study should be congratulated. This was a onerous task, the idea that anybody could randomize a patient with an acute pulmonary embolism I think was, you know, difficult to imagine in the United States. And I think all of us are grateful that this trial was able to be successfully executed. And obviously it's published in a high impact journal was published in circulation recently. So I think this is a tremendous achievement and it really does open the gates for I think many of us to, you know, really look forward and try and advance the science for this field. But there's a lot of questions that this trial brings up. And I'm going to, you know, look to you Eric to get us started off with a hopefully a, you know, very honest conversation about this. What's your takeaway I know Jay, you know, some, some this up but you know you were at, at the meeting, and, you know, we were all obviously looking forward to this presentation looking forward to the data. But if you had to summarize this for your, you know, colleagues that are, you know, practicing interventionalists that are treating patients with with PE what's your take home message for those for those individuals. Yeah, thanks Rob, you know, I, again, I want to second your comment about applauding both Inari for performing the first randomized trial and helping advance our algorithms and how to select devices and then also the investigators for all their time and effort and commitment to getting this trial over the finish line. You know, I think a lot of us practicing and working in the PE space a lot of us also working on the new PE guidelines is, you know, this is a trial we all need. But it's almost a little bit premature in the context of what the evidence base needs to happen for endovascular therapy overall and, you know, we are waiting for a lot of randomized trials that are just demonstrating the benefit of what we're doing with catheter based intervention over anti coagulation alone, which in the perfect world would be already completed. In this context, though, many of us are treating our patients on a daily basis, and we need to know which devices to select. And my take home is as follows. First off, you know, I don't ever believe and I've never said that any one device is all you need for endovascular intervention. Many of us practice in large settings or small settings but with complex patients and complex anatomy. PE care is an everyday 24 seven program. My partner Julie Bowman's on and saved my coverage yesterday or Sunday for PE so you know we really rely on both of these tools for different situations and so you know when I think of this trial and I think of the devices. The patients that get into this trial are not necessarily how we're using these devices. In our program we use catheter directed thrombolysis for patients who are at very low bleeding risk have potentially more distal clot that we want to address that may not be easily addressable and sometimes just logistical of who's on call and who feels comfortable with the device that may be needed for that patient. So, you know, when we've now put in the context of this trial how does this help me with our algorithm well my take home is as follows one. Both of these devices seem to work well. Both of them seem to be effective for treating PE, when there is the ability to have a patient who can tolerate either treatment, and which has anatomy that favors treatment with either device. We have a lot of additional endpoints that are valuable and require more investigation in particular the readmission data but are not necessarily where our minds are at right now when we're really thinking more about the acute needs of patients in the hospital without adverse events to discharge. And so I again think this is an incredibly valuable trial I think there are some important endpoints that differ between the two devices that need further investigation, but I feel comfortable that we have both of these devices available that both seem to be effective, and a lot of patients, and we should feel good about having the interchangeability of treatment strategies based on what you are doing at your institution what you're capable of what you're training for. What you're capable of what you're trained to do, and what your patients look like so that's kind of my superficial take home. Well said Eric Thank you and I should have mentioned this earlier anybody who's logged in tonight, if you have any questions for the panel, please type your questions into the QA tab at the bottom of the of the webinar we're obviously here to just, you know, share our own experiences and hopefully make you feel comfortable when you're taking care of your patients. A key, I'm going to direct the next question to you. Were you surprised by the results, or was it what you were expecting and again how do you take the results back to your own practice at at your institution I, I know we can all pivot to our own respective trials and I would ask that we all sort of hold on to those thoughts specifically as it relates to peerless one were you surprised by the results. You know, I think when the results came out was when I first really dived into the design of the study, and, you know, the patients included, and, you know, looking at the design as a whole. And in retrospect, it's not too surprising how it turned out so you know you've got two pretty effective therapies technically that, you know, seem to do a good job for intermediate risk patients for our surrogate outcomes that we've kind of designed for these, you know, preliminary studies is what I would say. And then, you know, looking at the question of clinical deterioration, which I think is a very important endpoint. You know those those differences are not that great between the two studies and certainly it speaks to one of two things either the therapies are not any are not different, or the event rate for clinical deterioration this population is very low. So to tease this out would require thousands and thousands of patients. So ultimately, it's not a surprise to me that the length of stay was in favor of large bore mechanical thrombectomy it's not a surprise to me the procedure time was shorter in the catheter directed thrombolysis group. And it's not surprising to me based on the baseline characteristics that not many of the patients clinically deteriorated now, you know, the bleeding rate. It's, I think, as we've become better as practitioners taking care of PE patients overall, our ability to really kind of, this is an unblinded study we're still doing a lot of other interventions, along with just catheters. So the overall health of this population kind of speaks, I think, to also the way we've improved in taking care of these patients so you know those are some of my takeaways, without without running over the entire conversation so I'm pleased to hear other people Thank you. Okay. June, I'm going to pivot over to you. The trials been out now for a couple of months, and you're the co director of the pert at a very very large teaching institution in Ohio. Has it changed your practice, are your colleagues talking about this. Obviously you're, you know, one of the leaders of the team with, you know, multiple specialties interacting. And, you know, this was a well recognized trial there was a lot of media with this and so what are people happening at your institute, what are people And what are you looking forward to in terms of any changes at all in the next several months. Great question Rob and I think to Eric's point, a lot of us have already established our practice pattern right and to me this trial. Exactly what he said, it didn't really show me anything that was surprising, right. The mortality was the same the bleeding was essentially the same in this very specific patient cohort. So I would say it hasn't really changed our actual practice, our institutions, a little bit different. There's essentially four of us doing PEs throughout the system and we have, we have like seven cath labs for us to be in the same institution. From one day to the next day is actually virtually impossible. So out of necessity, we are stuck with a essentially a single treatment single day treatment algorithm as much as we can, just because of geography. So for us, our institution actually does a lot of thrombectomy for that reason to stick with a single session therapy. So I'll say that it hasn't really changed the algorithm too much. Akin to what Eric had said, if a patient has very distal clots, for example, I do envision that these are the types of patients that would benefit more so from catheter directed thrombolysis, as opposed to thrombectomy, given the distribution of thrombus. I think what's important really is how do we manage these patients that are truly in the intermediate to high risk category, where we don't know for sure that doing thrombectomy or catheter directed thrombolysis is the appropriate thing. And as you know, the clinical trials that are ongoing and future clinical trials will be important and key to answering some of those more pertinent questions. Extremely well said. Thank you so much. Julie, I'm going to look to you. You know, Eric alluded to this that you've bailed them out over the weekend. And I know that you're a very, very visible clinical leader up in Boston for your team. What is your breakdown now in terms of catheter directed lysis versus thrombectomy? I'm well aware that you're all running many trials up there, but in the absence of somebody who's being enrolled in a clinical trial, what's your breakdown currently? And then do you think that this trial release is going to change that breakdown? Yeah, thanks, Rob. You know, I would say we're always trying to enroll every patient in a trial. I think any place that has trials, that's always number one. Are they a candidate? Certainly, if that's kind of off the table, I would have said probably before peerless, very heavy towards mechanical thrombectomy in our practice. We've been doing mechanical thrombectomy for years now. So I do think user experience and comfort plays a large role. And that's actually something I think worth mentioning when we discuss any of these trials. Trials are typically done in centers that have large volume and with high frequency users. And so there is certainly a learning curve to these devices. That's something we always have to think about when they actually get used in the real world. But certainly in the context of a trial, a little bit different. In our practice, maybe 90-10 if I had to give you a number in terms of mechanical versus lysis. That said, lysis is a very quick procedure. Most users are very comfortable doing it. And so that makes it a little bit more usable, if you will. And obviously, this trial, we did discuss it in our quarterly PERT meeting. We always talk about recent data. And it actually paints lysis in a pretty good light. And so we did just do a lysis last week. So we're certainly still doing it, but heavy towards the mechanical aspiration. Thank you. Perfect segue. I'm going to close this section out with you, Jay, and virtually hand off the moderating duties to Eric. Jay, this was touched upon earlier in the session, but the safety profile of both of these therapies was actually, I think, a little bit better than people were anticipating. The major bleeding rate was 7%, which is, I think, most people think is very realistic. The ICH rate was extraordinarily low. And I know you've been spending a lot of time trying to think about what the next trials should be. You're leading NRE's next trial. How do you think that this informs all of us about the safety of the endovascular therapies right now? And how can we all use that to try and plan the next set of trials? And now I'm going to stop moderating. I'll hand it virtually over to Eric as you answer that question. Yeah, thanks, Rob. Yeah, I guess I'm on an island here, right? I actually think that the peerless trial did change one specific thing for me, and it alludes to what you were saying. It changed how I approach patients and consent them. And that was particularly the case when we had these options. We had the options during peerless when we were consenting patients. And we had a certain risk profile in mind that was variable between the two procedures. That using Lytics was perhaps associated with more major bleeding. It was 10% in Seattle, too. And a little ICH risk, which is stochastic, but is known to occur with TPA usage. And on the other hand, using large-bore mechanical thrombectomy, which might be associated with more on-table clinical decompensations, naturally, because you're putting a large catheter up there, maybe more pulmonary artery injury. So I thought these were kind of competing safety profiles. And at least in this low-risk, bleeding-risk, intermediate-risk population, that really proved not to be the case. Honestly, the clinical deteriorations were about equal between the groups, maybe a slight numerical difference in favor of mechanical thrombectomy, but statistically equal. And then the bleeding was dead even, 6.9% in both groups. So this makes me take a step back and say that when I'm thinking about these two therapies, I'm not thinking about safety differences. And I think we have to think more about efficacy. And what is efficacy, and what does it mean to us? And to me, efficacy means the following, potentially. And we've used the RVLV ratios, or surrogate endpoint for efficacy, for a long time. But we often think about clot resolution, on-table clot resolution, or perhaps short-term clot resolution as an efficacy endpoint. We think about functional status changes in the patient, hemodynamic status changes in the patient. And a key question, I think, as we start to think about these therapies going forward is, how do we demonstrate those differences in efficacy against one another? And then also, most importantly, as Eric alluded to at the very beginning, against anticoagulation alone, which we'll reiterate remains a standard of care and all guidelines for this population, despite the popularity of these therapies and the viewers of this podcast. There was one question that just came up in the Q&A. Thank you, who submitted it. And I'm just going to throw it out there before we transition to the next section. And the question is specifically, if you don't have a patient with an absolute contraindication to a fibrinolytic agent, how do you decide to use a thrombectomy device versus a catheter-directed lysis infusion? A couple of us sort of touched upon this. If you have a symptomatic patient with predominantly thrombus at the segmental or sub-segmental level, I think many of us sort of echo that we don't necessarily feel the need to put in a very large-bore system that might not really move the dial for that patient. And a lot of us feel comfortable perhaps putting in CDT. Does anybody else have any other ideas for that? I can just tell you anecdotally at our institution, if there's a concern that the presentation is maybe acute on chronic or subacute on a chronic baseline, we're probably not going to go with a large-bore system. We're going to be much more comfortable going with a fibrinolytic infusion to just debulk the acute thrombus and bring them back to baseline. But anybody else who wants to chime in? Because it just came through the Q&A. A couple of thoughts here. Number one is in a patient who might be really teetering more into a high-risk category that are very tenuous, you may want to consider large-bore or medium-bore thrombectomy just for better hemodynamic control up front. As you know, CDT takes a few hours for it to really infuse. So that would be one consideration. In those patients, I would probably choose CDT specifically. You can use the IJ, very simple procedure for really morbidly obese patients. Excellent point. Anybody else? I just want to make a comment. Real quick. It'll be interesting as we have newer algorithms that are moving to on-table treatment with catheter-inducted thrombolysis. Julie, are you going to make a comment on that? Julie, you continue. Well, I'm going to run the next section, so I'm going to let you continue. Yeah, we'll know that. I mean, that's really currently our biggest decision-maker is how much time do we have? Because if we have a little bit of time and we want to get a little distal thrombolysis happening, we'll do CDT. But if we really need to offload the heart, we need to actually remove that obstruction, then we're moving towards aspiration. But with new trials coming up for on-table protocols, it's going to be really interesting how that field changes for us, because time might be taken off the table as a primary decision-maker. Yeah. And just for people to know, Thrombolax is running currently a trial looking at an on-the-table algorithm. They have some preliminary data that was supportive to move forward with a larger study. And I know Boston with ECOX has looked into this as well. And so it'll be really interesting how we think about this. Because again, as we've seen, most TPA algorithms move to 12 milligrams or less. The theoretic bleeding risk that a lot of us had in terms of even how many patients are a candidate for CDT, that population has dropped pretty remarkably and is more often limited to post-op patients and people with cerebral mets or primary cancer. So it's interesting.

acute pulmonary embolism

mechanical thrombectomy

catheter-directed thrombolysis

treatment algorithms

therapeutic approaches