Chapters Transcript Video Next Generation Devices Back to Symposium So, um, you know, moving back to the drug coated balloon, uh, uh, topic here, I just wanna talk a few minutes about next generation devices. Who've heard of Cyril Limus drug code of blues? Has Anybody heard of these? Anybody participating in any of these trials right now? No, OK, yeah, and, so, I mean, the, the question is, do we really need a new drug? And if so, why? Why do we need a new drug? How is it gonna work and which is the right one? And so I'm gonna just talk about that for a few minutes and then I'm gonna talk a little bit about instant restenosis. And we're gonna do the 3 clicks that Dua taught me. OK, great. So, you know, if you look at where our practices have gone, you know, we started at bypass surgery, PTA alone, bare metal stents. We got our first drug looting stent with Cook Medical, then we moved on to Boston Scientific's Alluvia stent. We went to pack the Taxel DCBs. Now we're at bioabsorbables. So what's next in our future? I think that's where we find the second generation DCBs to be exciting. And you know, a lot of people say, why do we need erroimus? Well, you know, we talked a little bit about this earlier, but Cerroimus is pretty much the standard drug used right now for coronary stents for, uh, most of the DCBs that are coming out outside the US on the market and so. Why has it not been developed for our lower extremity PTA DCBs, you know, really our, our, our workhorse DCBs, and you know there's many different properties about Limus that are favorable that I'm gonna go through, but Paclitaxel, the reason why we started with Paclitaxel and DCBs, it's really easy. So it's easy because it moves through the vessel wall. It's lipophilic, gets right into the vessel wall. You can make them into these little jagged crystals. I, I'll show you a picture in a moment that embed into the intima, and then they release drug and so it makes it a very easy DCB to create. The problem though is, is it the right drug, and I'll show you the reason why some people feel like it's not. And one of them is this who's had this. Happened to them before where they take their DCB out and they can see all this drug on the table. I try to keep that sleeve on, but you know how that sleeve works. Sometimes you can't get it. It pushes everything out and so you end up seeing Paclitaxel on your table or on your fingers and whatnot, and this is what the Paclitaxel looks like. And so really this is one challenge that has always been Paclitaxel's problem is loss of drugs. And we know that if you put a paclitaxel balloon in the blood, that 70% of that drug just washes away. It actually never gets to the target lesion. Probably about 15% actually gets to the target lesion. Another 15% stay on the balloon itself. So we have some troubles with just how do we coat balloons and what the proprietary value look of the crystalline paclitaxel is. The other one that people talk a lot about outside the US more than the US because we don't have options is slow flow. What happens when that Paclitaxel, which is a larger particulate, moves downstream? Now again, most of our PTA DCBs in the US are for FM pop and a little bit probably more used for cloudins than CLTI. So we don't have the experience outside the US where they have below the knee DCBs. But if you're working in Smaller vessels and have more particular embolization, you could imagine that can lead to some consequence. And in this study by Eddie Choke and others, this really looked at uh availability of slow flow phenomenon, the SF versus non-slow flow. So 88 patients, 7 had slow flow, and really there was worse outcomes among those that had slow flow, in particular looking at the amputation-free survival. So, how does Limus fix this? Well, a few things. First off, Limus doesn't kill cells. So we think of paclitaxel as cytotoxic. Some people use the word cytocytal, so they don't have to have the word toxic in the statement, but it is a cell death. And so that's why you can also see late lumen enlargement. You start starting sometimes seeing that the vessels actually can increase in size over time because you're you're killing tissue. But you're killing the media, you're killing. Like the meat of the artery. So we don't really know if that's the right approach, but like I said, it's the best approach because we could get Paclitaxel on a balloon to the drug and or the vessel wall so we have a therapy that's available and working. Limus arrests cells, so they don't die. They just stop turning over. And the problem though is you have to have the limus there long enough so they stay arrested. If the limus washes away, they're going to start functioning again. And so that's why we have stents. With polymers on them in the corner is that they elute drug with that polymer over time. The stent keeps that limus right against the wall, and over time that drug's permeating into the vessel wall. Balloons, we can't do that, right? It's one-time treatment. You're out of there. You're not leaving anything behind. So we got to be creative. How are we going to get this limus that just wants to wash away into the drug wall and have it stay there so that cell arrest is long enough for the vessel to heal and move on and not create all that new tissue. And so the other aspect of Lymus that people really like is it has some anti-inflammatory component as well. And you have to remember that most of or most of restenosis is triggered by early barrow trauma. Early trauma to the vessel wall from the balloon angioplasty causes both an inflammatory and thrombotic response, and that's why we have to stent sometimes. But if you could shut down both that inflammatory part and keeping that cells from making that tissue in response to the treatment, then maybe we could get longer term patency. So, let's talk a little bit about where Limus is going. So Limus, again, just like Paclitaxel needs to get into that vessel wall. You can see those arrows pushing it, but we need to find ways to package Linus to get it there because it just wants to wash away. It's hydrophilic, uh, hydrophobic, and whereas the, the pachytaxel particles are lipophilic. They want to go straight. Through, so all these new devices create waste to encapsulate limus into these fatty particles, phospholipids. You'll hear these nanoparticles, micro reservoirs. Anybody can call them whatever they want, but all it is is phospholipids wrapped around the limus so it can travel, can be lipophilic, travel to the vessel wall bed there and elute the drug. So, let's talk about above the knee novel DCBs first. So, uh, who's heard of Sarona? Anybody heard of Sarona? Uh, it's probably the trial to know a little bit about because this is gonna set kind of the standard moving forward of why we think Limus works. So in Sarona, this is an investigator initiated study by um Alf Teitweger. I can always say his name right, Tyreger, Ty Grabber, uh, and colleagues out in Germany who randomized patients with standard approved PTX devices, all different types, versus you can see my. Listed in the bottom right versus uh magic touches, concept Medicals, Lymus DCB SFA disease only and they looked at one year endpoint. So this is a head to head trial. Can Lymus be as good as Paclitaxel one year randomized trial. And what they found was that one year freedom from CDTLR primary patency was overall similar between Cyra Limus and Paclitaxel DCBs as a group. Again, these are a bunch of different. Paclitax with DCBs and they've now shown data out to 2 years showing that preserved patency between Paclitaxel and Lymus. So this is really the meat of it saying if you can put that limus on a balloon and get it to go to the vessel wall, you can get the findings that look much like Paclitaxel but avoid maybe some of that challenges with distal particulate embolization or any concerns people might have residual about the safety of Paclitaxel. So, concept has a number of studies going on right now. This is their balloon. They have a proprietary balloon. Again, I show you in these little depiction. Peter, it wasn't me. I'm sorry. The, uh, in the pictures here you can see these little encapsulations, so they have the limus in yellow and they put these phospholipids around it and now you can shove that into, um, the vessel wall, and that could be effective for embedding in the vessel wall and eluding drug over time. And they have a number of studies going on right now. One of them I want to show you is a real world study by Eddie Choke outside the US. And again, outside the US, a lot of these devices are available, so they have a lot more experience than us. So in this study they looked at 50 patients, 20 treated with em pop, 30 with below the knee, um, and with the Magic Touch BTA, uh. Drug coated balloon they saw patency rates and freedom major amputation through 3 years, 3 years that were quite exceptional. So freedom from major amputation for FM Pop was 93.3, below the knee 81%, kind of mimicking what we saw in the Sarona trial, showing that we can get packlitaxel-like results with these proprietary novel DCBs. Cortis. So Cortis also has a uh drug-coated balloon. I'm sorry that the slide got changed, but um in this drug coated balloon, they have something called micro reservoirs. Same idea, they take these little reservoirs that are lipophilic. They can fly through the vessel wall and they package in limus. And a little bit different for them is they package in limus with a little bit of like a polymer. It embeds these spheres in the vessel wall and then they break down at different times. So they call this a drug eluting balloon because the drug can kind of permeate. Some will be present right away. Some will be present over the following weeks to months. Most is gone by 90 days, but they can get closer to a 90 day window which looks much more like a coronary stent with a polymer. So, how are they looking at this? These are the number of trials that they're running right now. We've seen some data most recently from Solution SFA Japan, um, as well as Success. I'll show you this in a moment. And they're finished with their SFA trial in the US and running a BTK trial in the US. So, uh, this was their, uh, solution for SFA. 300 patients randomized to whether the solution DEB or not. Um, I'm sorry, they changed all the slides here, but they showed really, uh, let's see. Lucif 4 SFA. So this is, this is the trial going on right now. This is just finished. This should be presented at Viva this year. So there'll be the first US, uh, drug coated balloon trial for a Lymus DCB, um, that will look 2 to 1 versus PTA alone. This is data from the Solution SFA trial. So this trial was done in Japan. This was a single arm study of 130 patients with Fempoop disease, and they looked at follow-up through 12 months and beyond. They just presented their 3-year data in Japan, and you can see nicely now. 81% patency out through three years with the Lyus DCB again, really on par, if not exceeding where the attacks of DCBs have been. Now again, single alarm study, we got to see the randomized trial data to really feel comfortable, but showing that we can really be effective with these novel devices. Again, this is freedom from CDTLR of 94% with that Limus DCB. OK, let's go for uh below the knee now. So below the knee, we've struggled in below the knee. Does anybody remember the Impact Deep trial, Paclitaxel? See some head shaking? So this is a trial looking at a Paclitaxel DCB for below the knee, and the challenge was, it was an older formulary. There's a lot of drug that fell off that device and there's actually an increased signal of risk with the Paclitaxel DCB probably from all that distal migration. And so this kind of question whether Paclitaxel should be used at all below the knee if it's effective and also the safety. Um, and not to pick on, uh, Lutonics here, but Lutonics got stuck in the middle of this controversy because in the Lutonics BTK DCB trial, you could see at 6 months they met their primary endpoint in that figure. Standard PTA is orange, DCB is blue, but at 1 year, those curves went back and kind of narrowed in, and FDA won't improve them based on the 1 year data. So we're stuck without a below the knee solution. So can these different platforms work for below the knee? So these are different studies that have looked at below the knee targets. Most of these are real world registries. Again, there's IDE randomized trials for both Magic Touch and the corded solution for below the knee in the US right now. So we'll know this soon, but we're seeing more and more data that suggests that this can be effective even below the knee. So I'm gonna stop there. Any questions real quick? I'm trying to get us a little bit back on our timing, so I apologize for talking fast. But anybody have any questions about novel DCBs? Better than everybody here, have they ever looked at at at utilization of NC balloon scaffold as opposed to using a regular because it almost seems like when you're using a regular balloon unless you are going super high pressure, you're not getting routine adequate full expansion, which means that the drug is not embedding in the same way throughout the entire balloon. Yeah, that's a good question. I'm not sure that they've looked at the type of prep device. I'll tell you some of the failures, I think, is one, we're really bad at sizing, and this is why we've had the IIS conversation a few times is if you do a trial and if you just go algorithmically, an average tibial is 2 millimeters, and you use a 2 milli DCB and it's float in the middle of the vessel. You're not gonna get any benefit from that. And so we found that an average, and, you know, proximal tibial is probably 3.5 millimeters. So you have to size well for these devices. And then we talked a little bit about vessel prep. You gotta make sure that if you have calcium fibrotic disease that it's addressed, um, and maybe the NC plays a role in there. So it's a great question. OK, we're gonna keep going so we can get everybody to break. I'm gonna give one more lecture here and then I, I will promise you I will keep my mouth shut for a little bit. Um, OK, ISR, who's had ISR in their practice? I hope I raise their hand because you're lying and you don't practice if you haven't an ISR. unfortunately. So I'm just gonna walk through real quick um in stent restenosis and definitive treatment. So, we'll talk a little bit more in other sessions about vessel prep and ways to address neo atherosclerosis, neoenteral hyperplasia, but I'm gonna talk a little bit about definitive treatment. Before I get there, do people understand the difference between neoenteral hyperplasia and neo atherosclerosis? Anybody know the difference? No, I'll just orient us. So real quick, the common response to a stent is a hyperplastic response. The cells want to keep making tissue, and the neoinimal hyperplasia, we call it NIH, just looks like bland tissue. It's almost just like collagen and fibrotic tissue. If you look on Ibis or your angiogram and you see calcium in the stent, that's no longer neoentomal hyperplasia, that's neo atherosclerosis. So that's like a new plaque developed. And it's really important because sometimes you will see that new plaque will actually form in a stent, and you'll cross and it looks like you're sub-enamel in the stent. And it's because you are, you're in a new layer of plaque, and you're sub-inel to that plaque. Neoentval hyperplasia is much less common. You're just gonna see that you cross and traverse the planes of that tissue. Now, how do you treat that? Well, it can vary a little bit. Laser works really well on neoenteral hyperplasia. It's really good at burning away just tissue, but it may not work well on calcium and neo atherosclerotic plaque, where you might actually need an atherectomy. Device or a lithotripsy device or some other device. In addition, we also know that a lot of these stents get mixed plaque and thrombosis. So it's really important to think about that a little bit when you're using your devices for in stent restenosis. You can have some severe neo interval hyperplasia, neo atherosclerosis, and superimposed thrombotic material. And that's why a device that does multiple things, including aspiration could be effective. So, let's talk a little bit about where the guidelines recommend definitive treatment for ISR. We're not gonna focus on vessel prep. We're just gonna talk a little bit about the definitive treatment here. So, here's a case, 75-year-old diabetic, um, stage 3 CKD, uh, she worked at, we have only CVSs, not Walgreens and others in, in Boston, CVS, um, and she was just getting this, um, long-standing claudication. And then I got a call from her podiatrist that She had r pain and her toe looked bad. That was the comment, you know. And so, of course, I got her in as soon as I could. Again, you know how much I love flat lines on uh ABI PBRs, but you can see she had no pressure down to her toe, um, and we knew we had to bring her to the lab urgently. And so we brought her to the lab. Um, this is her angiogram. You can see a severe lesion in that mid-SFA and then occlusive disease, um, down by P1, and we're able to, uh, and this is an angiogram laid out here. So, you know, we always show you our best cases. We're able to cross this, DCB this, and then I put a short, I had a little bit of dissection. I decided to put a short standing kind of close to the abductor canal. So I left her with what I thought was a good. Good result. We got our rest pain gone and we're feeling really good. But you know, if you go back, she had every telltale sign for a stent to include diabetes, poorly controlled risk factors, advanced renal disease, older woman, these are the ones where we know the stents are more likely to reach stenos, and it's a little unpredictable on timing, but that you have to be thinking about that with your intervention. Those are all significant risk factors. So, everything looks good. We do great. She comes back six months later and now her toe, same toe. So that's continued to evolve even though we admit fixed ischemia. We go back. This is her post-intervention, um, ABI PVR is not perfect, but you can see still, she still has some, um, you know, small vessel disease, but her, her big vessels ABI was 0.9. Now again, she's back down to 0.2 in her toe. 6 months, you know, and I felt really good about that intervention, and this is her six months later. So, I hopefully, I'm not the only one that's seen this. Everybody raised their hand, that's why I made you do that first, so I didn't feel bad. Um, but, you know, this is, this is a pattern that we run into somewhat frequently, right? So, we gotta do something now for her. What do we do? And we'll, we'll go through that in a moment. OK, so remember, in stent restenosis is a combination of, of challenges, right? So you get that vessel injury from treating the initial lesion. We talked a little bit about that barrel trauma. You get inflammation from stent edges, you get that neo interval hyperplasia, all the tissue, or you get the neotherosclerosis, that's typically a longer timeline. So usually neoenteral hyperplasia is 6 to 12 months, neotherosclerosis after a year. But that inflammation pattern. is what really drives this whole process and in my practice, you know, I think that it's really key that if we cannot stent again, that we're probably for the better, you know, more stents in there, smaller lumen, more likely for thrombosis, more likely for less, uh, opportunities for treatment in the future. So really thinking a little bit about how to get a really great result without having to reign it would be one key, but we'll talk about the different strategies that are available. So the nice thing for DCB is that it's actually really data driven and actually after Levant2 Bard BD decided that they were going to look at a larger registry that included patients with instant restenosis. So they had their global registry, 691 patients, 89 pre-specified ISR subgroup. And what they found in that group was that people overall, each of these curves represent a different subgroup. Black is everybody averaged. Light blue is long lesions. Dark blue is instant restenosis, and pretty much you can see that everything looked pretty similar. We expect ISR to be a little bit worse than a long lesion, but they're able to maintain pretty significant patency with only a DC. Treatment for instant restenosis. I highlight here TLE-free survival of 90% through one year and 85% through two years. So in the real world, DCBs seem to perform very well for stents. Now, if you look at a meta-analysis now at a patient level, so I put all the patients from the trial, 3 trials together, this is published in Circ Interventions again, DCB therapy. Did much better at one year than just a plain old balloon angioplasty, and that I think we could all agree with is probably not the right strategy and it favored across all trials that looked at this in a randomized approach. So we really are seeing that DCB is a great strategy for treating the vessel when it's definitively already been prepped with some sort of device um to get you long term outcome. What about covered stents? Who puts covered stents in for inwardly for ISR? Anybody? Routinely great. So we got a couple and a man on the states do that routinely. So you know there are very reasonable data to support that. Again, I think a lot of us are concerned about thrombosis with covered stent grafts and particularly in smaller vessels and below the waist, but this is data from a randomized trial looking at or a single trial looking at 86 patients with ISR, and you can see here this is primary patency in red, primary assisted patency in blue, and secondary patency in green, and. Overall, if you realign stents with a covered stent, you do fairly well again through both 1224, and this is 36 month data. So this is a very reasonable strategy. I think again it comes down to the risk of uh thrombosis. So I use this kind of if I've interviewed 123 times, I'm still just dealing with the same issue. I think that's where I usually go to a covered stent. Um, obviously if you have a complication you're gonna use a covered stent as well, and those do happen. OK, Silver PTX. What about drug eluting stents? Anybody put a drug eluting stent within prior stent? Great, yeah, so that's also a strategy that I've used when I can't get enough of that tissue ablated. Or again, I've gotten areas where it looks like I've dissected inside the stent and I have a flap or I can't get it removed. I've done this and relayered with drug eluting stents. So Silver PTX was a single alarm study where they looked at 108 patients who had uh ISR. And they again showed very similar findings from covered stents um that you can get right around those mid-80s patency with a drug eluting stent within a prior stent, whether it's a bare metal or not. So I think this is a really nice data showing reasonable freedom from TLR. Again, I really like a DCB stent-free approach. First, it gives us more options because this may continue to happen, but DES and a covered stent in select situations may work. I didn't say, um, I didn't say bare metal stand. Who puts a bare metal stand in for ISR? So good. You passed the test. Uh, that is actually not recommended and has not been data-driven. This is really a hard, uh, meta-analysis to look at, but pretty much right here, what it says is if you do some sort of vessel prep with DCB, um, that tends to be the best long-term strategy for ISR in this meta-analysis So if you look at the sky guidelines, they have an appropriate use document. Green is good, yellow is up to you, red is don't do it. You can see across the top PTA specialty balloons, bare metal stents, DES, DCB, and covered stent. This is not as vessel prep. This is as a definitive treatment. So the last thing you do, and you can see PTA, specialty balloon, and BMS is not indicated as a stand-alone definitive treatment. The only greens are really for DCB driven by data, and the yellows are two A's, meaning pretty reasonable data for DES and covered stents covered really for diffuse lesions. So if you think about your algorithm, I tend to prioritize DCBs. If I have a challenge keeping that stent open or if they've come back from more than one treatment, I think DES is very reasonable and covered stent in select situations might be a great option, in particular if that pattern continues to happen. OK. So this was us after DCB alone. I only show you great cases and of course she never came back and her life was perfect and that toe stayed on forever. So, but at least we got her back to where she was. I didn't have to do anything more than just PTA DCB, um, and you know, she actually did, did fairly well with just that treatment. OK, we're gonna skip extra cases and get you guys a break. So we're gonna break now for a few minutes. Um, I will show this actually. I'm gonna try to show this case later because that was that subinmo in a stent, um, but you guys can, uh, grab some coffee, and then, so we're gonna be back here. Tino Pena is gonna remote in for his talk. He had knee surgery. We'll wish him well, but he will be back on. But I think we have about 10 minutes and we're gonna get our remote fixed in the meantime, and we appreciate you guys, um, staying with us for the first session. Published Created by
Content on this site is intended for United States Healthcare Professionals Only
