BackTable / VI / Podcast / Transcript #407

Podcast Transcript: The Evolving Role of Drug Eluting Stents in PAD

with Dr. Eric Secemsky

In this episode of the BackTable Podcast, host Dr. Sabeen Dhand interviews Dr. Eric Secemsky about the efficacy of drug eluting technologies in vascular interventions, with Dr. Secemsky offering insight into his own practice. Dr. Secemsky is an interventional cardiologist practicing at Beth Israel Deaconess Medical Center in Boston. You can read the full transcript below and listen to this episode here on BackTable.com.

(1) Stenting Technology: Terminology & Definitions

(2) Properties of Drug-Coated Balloons

(3) Exploring the Efficacy of Anti-Proliferative Coated Stents

(4) The Safety Profile of Drug-Eluting Stents

(5) The Stenting Algorithm for Peripheral Arterial Disease

(6) The Role of Combining Drug-Eluting Stents with Balloons

(7) The Value of Using Lithotripsy Prior to Drug-Coated Technology

(8) Using Reintervention Prediction Models to Improve Patient Selection

(9) The Economics of Using Drug-Coated Technology

(10) The Future of Drug-Coated Technology

This podcast is supported by:

Cook Medical Zilver PTX

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The Evolving Role of Drug Eluting Stents in PAD with Dr. Eric Secemsky on the BackTable VI Podcast)

Ep 407 The Evolving Role of Drug Eluting Stents in PAD with Dr. Eric Secemsky

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[Dr. Sabeen Dhand]
I'm Sabeen as your host today, and I'm happy to welcome Dr. Eric Secemsky from Beth Israel Deaconess in Boston. Welcome back, Eric.

[Dr. Eric Secemsky]
Thanks, Sabeen. Pleasure to be back.

[Dr. Sabeen Dhand]
Absolutely. I think we've had you on for a couple of times, and every time has been great. This time, we're going to be talking about the drug-eluting technology. Eric, you've done a lot in drug-eluting technology in the vascular space. What piqued your interest and drive to go full force into this realm?

[Dr. Eric Secemsky]
Yeah, it's really twofold. It's always an interesting conversation to have with specialists outside of the cardiology realm. In interventional cardiology, on the coronary intervention side, this is our lives. We've grown up with the evolution of drug technology. When I went in to start doing my diagnostic angios as a fellow, we still had bare metal stents on the shelf and we had the first generation and then second generation drug-eluting stents. Now we even have a third generation. So we've watched this technology evolve to the point that we don't carry bare metal stents in cath labs anymore.

Again, if you go back 10 years, you look at the patient, you'd say, oh, listen, they might have an issue that they come off their dual antiplatelet therapy early. They're not really good at taking meds long-term. They might have some bleeding risks. Let's put a bare metal stent in. We know the long-term data is not as great, but it saves us some risks on the short-term. Now we have data showing that even drug-eluting stents for coronary purposes can go along with a low duration of dual antiplatelet therapy of up to one month. We just got rid of bare metal stents altogether. When you look at an interventional cardiologist and you talk about drug-coated technology, this is our bread and butter. That was really what tied me in then to the second part of that, which was the paclitaxel controversy, which I know we'll speak about and how my passion for drug technology and then working through that real challenging situation blended my interests in the coronary space to the peripheral space.

[Dr. Sabeen Dhand]
That's awesome. Yeah, we'll totally get into that. I know you've been on before, but just for our listeners who might not know you, can you give us a little introduction about your practice and what your main focuses are?

[Dr. Eric Secemsky]
Yeah, absolutely. I'm an interventional cardiologist by training. I trained over at the Mass General for most of my cardiology and interventional cardiology training, and then I did dedicated training in vascular intervention fellowship and in vascular medicine. I moved over and started a vascular intervention program at the Beth Israel Deaconess Medical Center in Boston, which is about three miles from the Mass General. I didn't have to move too far. They weren't doing a lot of these procedures at the time. There's been a history of doing these procedures, but it was a little bit quiet. I rebooted the program. I split my time when I'm in the cath lab between coronary intervention, which is about 30 to 50% of my time, and then peripheral intervention, which is the other half, if not more. I really, even on the peripheral side, my main interest is lower extremity arterial disease.

You can fill my day with lower extremity cases. I'd be a happy guy. Doesn't always work out that way. So I do a lot of infraingular and above the waist interventions, whether it's claudication or CLTI. Then my other pocket of procedures really focuses on pulmonary embolism interventions. That's been a big part of my career, and more recently, renal denervation. I do all the other IVC filters and DVT. I always call myself, I got a little bit of IR, a little bit of vascular surgery, and a little bit of interventional cardiology mixed into my practice.

[Dr. Sabeen Dhand]
Dude, I'm not surprised. I went to med school with Eric, and he's probably the most smartest person I've ever met in my life.

[Dr. Eric Secemsky]
That's a danger. We're all screwed if that's the case.

(1) Stenting Technology: Terminology & Definitions

[Dr. Sabeen Dhand]
No, totally. So okay, let's get back to drug-eluting technology and specifically drug-eluting stents. There's a lot of vocab and terminology thrown around, like scaffold, drug delivery method, drug-- Tell us a little bit about what those mean and how they're different in different stents.

[Dr. Eric Secemsky]
Yeah, absolutely. Most of the backbones of our metallic stents in 2023 are really the same framework of the metallic components, which I won't go into. We've gone back and forth from same stent and scaffold, which in many places represent the same technology, but we also know that a Supera stent is built differently than a self-expanding stent. Then also, recently, we've been reintroduced to the bioabsorbable scaffolds. The scaffold terminology is becoming more relevant in meaning that there's an implant after you've intervened.

The makeup of a drug stent, I say drug stent and not drug-coated or drug-eluting, is differs based on the technology. In the coronary space, again, there's three components to a stent. There's the scaffold, there's the polymer, and then there's the drug. The polymer is what elutes the drug over a certain amount of time. Now, the first drug-coated stent, and I'm using coating here, in the periphery was the Zilver PTX stent. That really changed the game. this has been on the market, I think it was around 2012, when it really got introduced into the US market. That was the first and only drug-coated stent and remains the only drug-coated stent on the market now. That is a metallic stent, again, with coating of paclitaxel.

[Dr. Sabeen Dhand]
By coating, what do you mean by coating? It's just attached to the stent?

[Dr. Eric Secemsky]
Yeah, and I don't want to say sprayed on, because I feel like that doesn't do justice to the technology but it's, in theory, sprayed onto the stent. I think that drug sticks around for about 90 days, if I'm right, and I might be off by a little bit. Then the properties of the stent go back into a traditional bare metal stent. Then we've been introduced to the Eluvia stent, the kind that got rolled out during the paclitaxel controversy. It had a little bit of a slow start, and then now has been more on the market. That one combines both the drug, the paclitaxel, the metallic background, the stent scaffold, and then a polymer. This is the first really polymer stent that allows for an elution of the drug coating. I think that they tell you around like eight months out to 14 months is when it really starts to elute off and then eventually turns back into a bare metal stent.

The goal of the polymer was to mimic the elution of drug during the highest risk period of restenosis, so that if you believe that at the end of one year and going into two years is when most of your fem pop interventions start to occlude, that elution of drug might prevent that from remaining patent.

[Dr. Sabeen Dhand]
Essentially the elution allows the drug to be delivered longer.

[Dr. Eric Secemsky]
Exactly right. Again, you can mess with these polymers to change the elution properties. There was a little bit of controversy in the coronary space that the polymer itself can cause some inflammation and could be counterproductive. There's been a lot of changes in how we've designed these stents, and now even the polymer has become absorbable over time to really not leave anything outside of the stent behind. All this technology evolves from picking the drug. Right now we've been picking in the periphery, paclitaxel, that there's been interest in limus-based therapies. Picking up in some sense of polymer and in the Zilver PTX stent, just coating the stent with that drug and then the scaffold.

(2) Properties of Drug-Coated Balloons

[Dr. Sabeen Dhand]
Okay. Really essentially, how is that different in drug-coated balloons where obviously the "scaffold" is the balloon, but are they also using a polymer and then the same drug?

[Dr. Eric Secemsky]
Yeah, so the drug-coated balloons are a little bit different, because there's no scaffold to elute any medication or antiproliferative agent over time. You really have this one opportunity for a transfer of drug from balloon into the vessel wall. As we know, when you put a drug-coated balloon in the body, about 70% of that drug goes elsewhere, and about 30% of it-- Not in a dangerous way, but just it absorbs off. By the time you get the balloon actually delivered to the vessel wall, about 30% still on the balloon, and probably only about 10 to 20% get against the vessel wall, but all the different drug-coated balloons have different proprietal ways of packaging the paclitaxel onto the balloon. Again, now we've seen this with the limus technology, talk about nanoparticles and other microspheres, other ways to transfer, but the goal is that you got to package the meds to transfer into the vessel wall.

If you talk to Elazer Edelman, who made one of the first coronary stents, he likes to say that it almost tattoos the wall with the drug, so that you get as much of it pressed up against the wall, and then you expect for that to transfer into the vessel wall, deep in the vessel wall, and really contribute to the anti-proliferative properties of the paclitaxel for the currently marketed DCBs. But there's no polymer, there's no long-term elution, you don't leave anything behind. As much gets transferred on that one therapy, that's what you're left with, and hopefully it's enough, but I'm sure there's some situations where not enough is transferred, and we know that with calcific disease.

(3) Exploring the Efficacy of Anti-Proliferative Coated Stents

[Dr. Sabeen Dhand]
Yeah, you mentioned paclitaxel and limus-taxol and limus are really the two drugs that have been used on stents. As they're anti-proliferative agents, are there other agents that have been looked at too or are those are the only two that are shown to be effective?

[Dr. Eric Secemsky]
I'm sure there's been interest in many different agents for decreasing anti-proliferative properties of restenosis. A lot of what we're doing in the periphery has been driven by how drug technology has evolved in the coronary space. Back when the first-generation coronary stents were made, they were Taxol, they were taxus-based, and the stents themselves worked really well. They prevented early and midterm restenosis that we're seeing with bare metal stents, but the problem in the coronary stents is that it almost worked too well that there was risk of late occlusion, we call it-stent thrombosis, because of potentially paclitaxel being too aggressive and not letting the stent really endothelialize into the vessel wall. Then that metal scaffold was a nidus when it came off your antiplatelet therapy for thrombosis.

That's why in the peripheral world, two things happened. One, we started using dual antiplatelet therapy much longer to prevent that late occlusion. Then we evolved from paclitaxel to limus based, and there's a couple different limus drugs. That really- the limus with the polymer and the coronary space allowed for this more consistent elusion and more really successful long-term reduction in thrombosis rates, that's become the standard of care in all our stent style or limus space. In the periphery, you have to think of the peripheral space a little bit differently. First off, it's a larger vessel, so occlusion rates are going to be different. Coronary vessels are three millimeters, and SFA is six to eight millimeters. You don't have the same small vessel that you worry about with the scaffold.

The other thing is it's in a very aggressive area for atherosclerosis, as we all know. You need a really effective agent there, and so that's where paclitaxel has been so successful is it's an aggressive anti-proliferative agent. It moves through the vessel wall very successfully. It's a very aggressive anti-proliferative agent, and that has made paclitaxel really an incredibly successful drug in the peripheral vascular space.

[Dr. Sabeen Dhand]
That's interesting. I was always thinking, I was like, why aren't- the limus has shown to be so effective in coronary. Why isn't just all the peripheral stents limus too? It's interesting that paclitaxel's stronger, and that's why. It's a bigger vessel.

[Dr. Eric Secemsky]
Yeah, there's a lot of differences between the two of them, and we can nerd out about it, I'm sure, for a while. I think the thing that I think about a lot is they've looked at limus in the periphery before, and some of the biggest issues is just it's harder to package and deliver successfully through the vessel wall. The older technology, and there's been some other stents also that have had limus on them, haven't been successful. Now the newer technology, we know there's a lot of interest in this across industry, has different mechanisms for packaging that limus that could, in theory, be successful. Most of that's being advanced in the below-the-knee space right now, where paclitaxel hasn't shown benefit. I'm sure we'll see more above the knee as well and on stents. The last comment there is that when you put the limus with a polymer, it's much easier to deliver, just like in the coronary stent. That might be in the future also, is that paclitaxel stents work great, we'll see maybe some limus stents, we'll have to see if they work as well as a paclitaxel stent.

(4) The Safety Profile of Drug-Eluting Stents

[Dr. Sabeen Dhand]
Yeah. So 2018 was a big year for paclitaxel, and the whole debate came up about the risk-safety profile. What are your thoughts, now you've done so much work. What are your whole thoughts and overall opinion about the safety profile of drug-eluting stents and technology?

[Dr. Eric Secemsky]
Yeah, absolutely. I think that it's fun to sit here almost four years later. That was, December 2018 when it was published or five years later now, gosh. It's crazy to have lived through it, and we all lived through it together, and it's so awesome to see in our careers that there was this big controversy and that we almost got to live through the resolution of it as well. I think oftentimes these things linger, and they don't have the same ending, and it was really awesome. I'll just comment on that. The first thing is, I grew up learning peripheral intervention with drug-coated balloons and drug-coated stents as part of my daily practice. I always use this analogy when I speak about paclitaxel, is if you went to the cath lab and told me during coronary intervention, "Guys, I really need to get rid of every drug-eluting stent off the shelf, you can either bring back bare metal stents or you can only balloon." We would shut down. I think, and no one would agree that we can do our procedures anymore in the same way, and benefit our patients.

To come in and say, all drug-coated technologies needs to halt because of this alarm signal from this analysis is challenging. It was challenging for my own practice. I got involved because I'm interested in this, but obviously I got more involved, because it was affecting my patient care and I saw that it was going to affect patient care throughout the world. Now, something that a lot of us brought up from the beginning is this whole controversy was started on some shaky data. It's not that the trial data isn't sound. It's just that the trial data never was meant to examine mortality. When you introduce all these variables like loss to follow-up, repeat treatment, crossover, I think that it would create a very complex scenario where you don't really know what you're measuring in the end, because you don't know what that pathway, the journey of that patient was. The person who got randomized to balloon angioplasty in the original Zilver trial potentially went and got a Zilver stent. We saw that happened in a meaningful amount of patients, but they weren't being treated that way. They're treated as only in the balloon arm.

So there's a lot of nuance to that meta-analysis that wasn't adding up. Then we never could really demonstrate a mechanistic fashion of how a one-time treatment with what is relatively low-dose paclitaxel can cause such a high risk of death, 7%. That's just a number that- it's hard to think of things that can because 7% mortality.

[Dr. Sabeen Dhand]
7%.

[Dr. Eric Secemsky]
Right? Unless you're trying to kill someone. I think the most important thing though, and the FDA said this themselves is if it wasn't death, there would've maybe been a different response. Death is such an important endpoint to everyone, patients, to clinicians, to regulators, to the population level. Because it was such a important endpoint that was being presented as associated with these devices, the FDA had to take it seriously. Again, it was a really unique process watching industry come together and find out how to work together and then solve this issue. Clinicians and societies working with the FDA to find ways to support the process and independent investigators generating data to help guide the regulatory process.

Really a remarkable time for the vascular field. I think everybody should be proud how people came together, trying to do what's best for the patient, make sure the patient risks weren't there with everything, that we care about our patients first, that we're doing things with them in mind. In July of this past year, the FDA finally reviewed all the updated data. They had an updated independent patient data meta-analysis. They got the individual trial data with all these updated trials that had lost a follow-up, some newer trials that have longer term data. This was published in Lancet in October by Sahil Parikh, Bill Gray, Peter Snyder, and others. That really gave the FDA the confidence to say, we don't have a true sense that this association is actually real and that these devices are causing harm, and really reversed all their stances on paclitaxel.

[Dr. Sabeen Dhand]
Yeah. That was a very important article and stance. It was an interesting time to live through, because we all knew drug-eluting stents were working great and drug-eluting technology is working great. Having those challenges or saying, oh, having those conversations with those patients at that time five years ago, four years ago was difficult.

[Dr. Eric Secemsky]
Absolutely. I'll tell you something Sabeen. I was at VIVA sitting through a talk about durability of drug-coated balloons and drug-eluting stents. They're reviewing all this interesting data. It was so nice and refreshing to sit there. It wasn't about mortality, and it wasn't about how do I consent my patients, and how do we get through this controversy. It was about the data and the science and the technology. It was just really refreshing for us to go back to where we started and think about what a breakthrough technology does to a space like peripheral intervention.

(5) The Stenting Algorithm for Peripheral Arterial Disease

[Dr. Sabeen Dhand]
Yeah, totally. Along the lines of stenting, in the past, there would be "leave no metal behind." What's your general sense on your stenting algorithm for say, fem pop disease?

[Dr. Eric Secemsky]
Yeah, absolutely. Again, there's always different ways to break that down, claudicants, and CLI, CLTI. But in the average case, I think that the no scaffold or leave nothing behind approach is really sound in particular for specific lesions. If you have a very focal lesion, if you have a lesion in a very aggressive area that you know stent fracture could be an issue, Hunter's Canal, anything in the distal SFA pop, those areas, they're definitely going to benefit from having no scaffold left behind. That said, that's not the reality for the majority of disease that we encounter. We encounter today long occlusions, aggressive, hostile areas with calcification. We use reentry, whether we intend to or not. We use reentry, and that's where IVUS has taught me so much. There's just some areas we all know where you can try and try again, but you cannot keep that open without a scaffold or it may not be the right strategy for a very long occlusion. That's really where these stents come into play, the scaffolds. That's, for me, where I almost only use drug-coated scaffolds is for when I know that a scaffold-free approach is not going to work.

[Dr. Sabeen Dhand]
Yeah, perfect. Exactly. I was going to ask you, are you using bare stents at all?

[Dr. Eric Secemsky]
I can't.

[Dr. Sabeen Dhand]
Yeah. In fem pop segment, are you even using bare stents minus, obviously, interwoven Supera, but other than that, are you using bare stents?

[Dr. Eric Secemsky]
Yeah, great question. If anything, if I ever have to stent, particularly P2, P3, it's always a Supera. I won't put anything else in there. Honestly, anything from distal SFA to P3, I'm usually using a Supera. Anything that's not involved in that distal zone, I'm almost universally using a drug-coated stent. I've been using Zilver PTX for many years, including back to when I trained at Mass General. I also have an Eluvia drug-eluting stent. I had the opportunity to use and learn for both of these scaffolds, but that's my approach for any long segment fem pop disease that is not ripe for a leave nothing behind strategy. I think my algorithm has been successful.

(6) The Role of Combining Drug-Eluting Stents with Balloons

[Dr. Sabeen Dhand]
Yeah, I totally agree. I share the same opinion. What about now, you're treating a lesion, you're trying to not leave a scaffold behind, you do a DCB treatment, and then do you think there's an additive effect of having a DES on top of a previously treated DCB?

[Dr. Eric Secemsky]
Great question. Last year, I think it was in the Journal of Invasive Cardiology, we presented a series of patients treated with DCB and DBS, led by Aaron Armstrong and his fellow, Stefano Giannopoulos. It was a single-arm anecdotal study. Again, it's not life-breaking science, but the concept here was, is it safe? Is there a role for it? I think also, more recently, PK, Prakash Krishnan from Mount Sinai, published an experience of DCB and then Supera. My feeling is, and again, I'm going to put my interventional cardiology cap on. My bias and conflict here is, I believe in drug, and it's because of being an interventional cardiologist and living in that space for coronary intervention, is drug is the right way to get the longest benefit for a patient, to really reduce the risk of needing another procedure, coming back to the hospital, taking time off work, being bed-bound, whatever it might be.

I feel that I typically put a drug-coated balloon down in a lot of cases, even if I know I'm probably going to scaffold some of it. I still usually start with a DCB, because I see no downside. Then, from there, I can also focally stent or rely on the whole thing if I need to. I almost always use drug-coated technology in that same algorithm that I presented to you, long fem pop, outside of the distal SFA pop, I'm going to put in drug-coated or drug-letting stent. If it's the pop, I'm going to put in a Supera. I don't have many procedures where there's not some drug touching the patient. I don't think there's any downside for double treating. Again, I think that the drug-coated balloon and the drug stents might have different properties and when that paclitaxel might be most effective. I'm looking for a long-term benefit, and I think that the dual technology could have an impact, but at minimum, it's not going to hurt the patient.

(7) The Value of Using Lithotripsy Prior to Drug-Coated Technology

[Dr. Sabeen Dhand]
Sure. What about, do you think-- There's probably data on this too. What about lithotripsy before putting drug-coated technology, does that improve the delivery of the drug to the target?

[Dr. Eric Secemsky]
This is probably one of the hardest questions that remain, and it feeds into the whole idea of plaque modification and atherectomy, really, is what is the value of atherectomy? I'm lumping intravascular lithotripsy with plaque modification and atherectomy. One of the main feelings across the space is that atherectomy and plaque modification help in calcific disease, the transfer of drug into the vessel wall to be effective. This comes back to Fabrizio Fanelli, who had this really classic slide just demonstrating what happens with drug-coated balloons in calcific disease and the inability for a drug to make any penetration to the vessel wall.

The problem, though, is it's been really challenging in a non-animal model to demonstrate this clinically. There's been several attempts, anywhere from the VIVA reality trial, which used directional atherectomy with the DCB, to PAD III, which was a randomized trial of lithotripsy with drug-coated balloon versus drug-coated balloon itself. To your comment about IVL, the PAD III trial really was trying to do two things. One, show the early benefits of intravascular lithotripsy combined with a drug-coated balloon, which is standard of care. Then they looked at this up to two to three years. What they found in that trial was intravascular lithotripsy decreased the risk of bailout stenting. It was really a safe and effective way to prep before drug-coated balloon angioplasty.

The problem was the patency looked good in the long-term, but the DCB arm that didn't get lithotripsy got a lot of stents. It was really hard to understand the patency differences, if there were any, when you're comparing now DCB and stent versus IVL and DCB, and how much the drug impacted those long-term outcomes. The bottom line is, I do feel like if you have a cleft of calcium and you're putting paclitaxel on it, it's just going to be on calcium. Vessel prep's important. I use IVL, I use a little bit of atherectomy. I'm not a heavy atherectomy user, but more importantly, I think getting drug to the vessel wall is critical for long-term outcomes.

(8) Using Reintervention Prediction Models to Improve Patient Selection

[Dr. Sabeen Dhand]
Yeah, makes sense. Speaking of long-term outcomes, there's been a couple of predictability models, particularly one that's available online by Cook. Do you use that?

[Dr. Eric Secemsky]
Yeah, absolutely. Data is an important part of everything. In particular, these data models or prediction models to help really consult patients even before a procedure are critical. During the paclitaxel controversy, the question was, how do you identify a patient who's high-risk enough to get a drug-coated technology if you were concerned that signal was real? Cook Medical really led the way with their data. They had the longest-term data on the five-year data for the Zilver PTX stent had been published, and they were incredibly transparent. I think everybody in the field recognized that Cook took a leading position in terms of being transparent about their data and standing by their technology.

There's a gentleman named Aaron Laudis. Aaron was a statistician at Cook who's a wonderful guy. He actually went to academia, but still affiliated with Cook, but helped put this together with the Cook team, a prediction model, and they used their data and registry data to identify predictors of a higher likelihood of needing a repeat intervention. It was freedom from target lesion revasculization. They used a number of really available variables to help generate a really realistic prediction rate for the likelihood of repeat intervention. They have about eight patient demographic variables that are anywhere just from age, sex, diabetes, high cholesterol, smoking, claudication, or CLI. Easy stuff that we have on our mind when we're presenting any patient. Then if you have a diagnostic angio available, they had some lesion characteristics, length, reference vessel diameter, total occlusion, calcification, prior intervention, and runoff.

Again, there was about 15 variables in total, eight patient, seven from the lesion characteristics. You plug all these numbers in, and then they give you a really nice estimation of freedom from target lesion revasculization from 12 months through five years. When this started, I think that it was an opportunity to say, if we are going to limit how much paclitaxel we expose patients to, but balance that there is a risk of needing a repeat intervention if you use just a balloon angioplasty or non-coated bare metal stent, this is a good way to guide that conversation. If you had really high risk of restenosis, maybe it's like, let's just do it with the [unintelligible 00:28:25] with the drug-coated technology. Now, with paclitaxel being safe, it's not about reserving paclitaxel, but just thinking a little bit about how you leave a procedure. We all know that we don't want to aim for perfection, because that gets us in trouble. We also know that we got to go think about the risk, long-term risk for a patient, and that goes anywhere from their age, the severity of their disease, CLI versus claudication, to the lesion morphology.

This helps us just be realistic with our patient that you have a fairly high risk of TLR. We are going to be really aggressive with how we treat you, because the only way we know how to modify that if you're already going towards an intervention is to be really complete with our intervention. I think that's where this prediction model can be really helpful for that conversation with the patient and a reminder to the clinician about the risks of that patient.

(9) The Economics of Using Drug-Coated Technology

[Dr. Sabeen Dhand]
Yeah, and a follow-up to this prediction model and revascularization or repeat interventions, how does economics play into this? These stents are more expensive than your bare stent. For you and I who work at hospitals, it's a little bit different. For someone who is working at an outpatient center, it may change. How do economics play into the use of DES?

[Dr. Eric Secemsky]
It's a challenging question. Again, just like you said, when I'm in the hospital doing an intervention, I'm never reckless, but I don't have that spotlight on me because the package of that reimbursement is usually more than enough to cover whatever I'm going to do and more. The ambulatory space is different. I always joked about the first paclitaxel controversy. I was sitting on a panel at a conference called TCT or a couple months before 2018, before the paclitaxel controversy, and we were discussing the low use of drug-coated balloons in the ambulatory setting, which was driven by changes in reimbursement. They didn't get an extra payment for them, and it wasn't in the financial algorithm in most ambulatory settings because of the cost being somewhat prohibitive to the total needs of the center. As we fast forward to 2023 into 2024, we've got to really take a look at ourselves as a space. We have so much controversy right now with the New York Times article, and atherectomy in general, differences between specialties, and even beyond specialties, differences based on where you're practicing. I think at the end of the day, we've just got to find ways to move back to a patient-centered approach.

If we all agree that drug technology is proven to reduce repeat interventions and keep people out of procedure labs, it's got to be priority. That's got to be both on the ambulatory setting to find ways to make that financially solvable, but also on the industry side to think of creative ways to make these readily available for ambulatory settings that have different needs and differences in terms of their reimbursement patterns. I've seen and heard already that some more and more ambulatory settings are bringing in drug-coated technology and able to find methods to make the reimbursement and the payments doable. Again, we just have to hold ourselves to a high standard of putting the patient first and the finances second, but the finances are a real strain and they've got to come closely second.

(10) The Future of Drug-Coated Technology

[Dr. Sabeen Dhand]
Yeah, totally. Any particular trials that you want to highlight with drug-coated technology and DES? From a very basic trial, like EMINENT, right? You want to speak a little bit on that, and IMPERIAL?

[Dr. Eric Secemsky]
Yeah, absolutely. There are a few trials that are musts, and there's many trials out here, so I don't want to limit our conversation. I want to make one comment first before we go into IMPERIAL and EMINENT, but the Zilver PTX trial, Cook was ahead of the game. This was the first drug-coated stent technology, period, and they led the way this trial was done in the 2000s. 2008 or something around there. This was really a breakthrough technology that Cook helped champion and set the whole field in a different direction. It was just around 500 patients, and it was a complex trial, because the standard of care was still balloon angioplasty, so the primary randomization was the Cook PTX stent and then balloon angioplasty. Then, if angioplasty failed, there was a secondary randomization to either a provisional bare metal stent or a DES. Very complicated, and again, it goes back to why that trial was controversial in the paclitaxel setting, but the most important thing was they have data out through five years and now longer. If you continue to follow these patients out, they do really well with the drug-coated technology.

Everybody has a different definition of what well means. This isn't CLTI, typically, they're claudicants, but we know that patency, freedom from TLR, all of these were really improved out through five years with the drug-coated stent, the Zilver PTX stent. So fast forward to IMPERIAL, which was published, I think, in late 2018, and this was Boston Scientific's trial to look at the IDE, the approval of the Eluvia polymer drug-eluting stent, and they did something different than people were doing in this space. They compared it head-to-head with the market lead, the Zilver PTX stent. I think for a field, this is a really important trial to conduct, because we need these type of data to guide our decision-making. We need to have some head-to-head trials, and that's not happening from a regulatory standpoint, because the regulatory process usually just makes you compare to the standard pair, which some places is just plain balloon angioplasty.

It was important for us to say, how do these two technologies compare? The IMPERIAL trial showed some important stuff, and again, you learn more as the study ages. When we first started the trial, the IMPERIAL primary results published in Lancet in September 2018 showed first that there was non-inferiority, so there's no differences in terms of the ability of the Zilver PTX to perform- or I'm sorry, the Eluvia stent to perform to the level of the Zilver PTX stent. Now, again, this trial was around 460 patients, it was two-to-one randomization, so again, there are some limitations there, but then they said, they went on to the trials, they met non-inferiority, they could look for superiority, and there was some benefit at one year for the Eluvia drug-eluting stent over the Zilver PTX. Now, as you've gone on past one year, the benefit of that has narrowed, and really, how I look at it is these two stents together are really important- have effective stents, Yeah. Again, one year is not really what most of us, especially for claudicants, are thinking about, we want to get two, three, four years out of it.

The last study that you mentioned was the EMINENT study, and it's just worth commenting on, because again, as important it was to run IMPERIAL as a head-to-head trial, the question remained, well, what about our bare metal stents, and we haven't really seen a contemporary trial randomizing the best drug-coated technology to bare metal stents. The EMINENT trial compared the Eluvia stent to the average bare metal stent, and I think around 15 to 20% of the bare metal stents were Supera. It was a combination of probably best technology and average stent technology, but at one year again, there is a benefit of a drug-eluting stent over a bare metal stent, and we'll hopefully see some longer-term data on that trial, but overall, the bottom line is we've got some really good stent options right now. They're clearly better than PTA, I think we can all agree on that. They're better than probably an average bare metal stent, I think that's also clearly demonstrated now, and there's more trials now looking at the comparison of DCB and a drug-eluting stent, and there was a trial called the SPORTS trial that compared outcomes between bare metal stent, DCB, and DES.

That trial showed really a nice outcome for DCB, and I think that with DES, as needed, there's an algorithm to be had there, but DCB and Eluvia DES in SPORTS trial, which was presented at TCT this year, outperformed bare metal stent. I'm going to conclude my blurb here as saying that there's probably very little role for balloon angioplasty alone, there's probably a very limited role for bare metal stent, and probably DCB before bare metal stent, if you're going to use them, makes sense if that's financially possible, but I definitely think the future is in these drug-coated technologies.

[Dr. Sabeen Dhand]
What a changed from five years ago when we were dealing with this debate.

[Dr. Eric Secemsky]
I know.

[Dr. Sabeen Dhand]
No, this is obviously better.

[Dr. Eric Secemsky]
I know. It's great, though. It's great where we live in an abyss of evidence in the vascular space to finally have evidence to say that. I have trials to support each of those comments, and that's really what this field has needed for a long time. I'm proud that that's the direction it's gone.

[Dr. Sabeen Dhand]
Yeah. Next question is about future technologies, right? Are there any benefit of using drug-on-stent grafts, maybe the edge of the stent grafts or things like that?

[Dr. Eric Secemsky]
I love that question. I think about that all the time, because we were sitting up at VIVA talking about PQ bypass, as people are not familiar, the TTOR trial looked at this percutaneous bypass that you could perform along femoral SFA pop lesions, and we were just talking about cover stents and when they do fail, where do they fail. As you mentioned, Sabeen, they almost universally fail at the edges. I don't put in a ton of infrainguinal cover stents. I'm thinking more about that, in particular for ISR, there's good data on that, but when I do use them, I think that using a drug-coated balloon to really hit the edges is probably a good way to experiment whether that can reduce some of the restinosis when it does occur. I think that could use some more data. I can't give that a level one, but that's a great question. Something I've thought and talked a little bit about.

[Dr. Sabeen Dhand]
Sure. What about, there's other spot stenting, like Tacks and things like that, any utility. Any other utilities that drug might be coming out to? you mentioned bioabsorbable stents, too. I'm not sure, where are we at on those?

[Dr. Eric Secemsky]
Yeah. Tack is a great technology, and again, that is really meant to be a dissection repair device. I think it sits in its own space a little bit. If you really, as we discussed, buy into this idea of a really minimal, scaffold-free approach, Tack gives you the opportunity to really reduce the need of having a lot of metal and stenting a whole segment where that might only just need some repair. Really cool technology and really was a unique thing to come to market. I think that the big 2023 attention has been on the bioabsorbables, but primarily for the below-the-knee space. The bioabsorbables right now, most of the technology are combining an absorbable scaffold, and that's why we're moving away from the word stent, with drug. These drugs primarily are limus, because again, it's easier with a scaffold to package limus on there than to package it on a balloon in some situations.

[Dr. Sabeen Dhand]
We know limus works well, with our coronary DES proximal tibials. Those stay open.

[Dr. Eric Secemsky]
Exactly. Absolutely right. That's what everybody says, right? They're like, one segment that, you might get horrific restenosis below it, and then you have this beautiful stent there. I'm excited, and I'll put the plug in there that maybe you'll invite me back in three or five years, and we'll talk about how that below-the-knee algorithm has changed. I think that the idea of the future is proximal tibials will get a scaffold. Right now, we're thinking that the bioabsorbables could be the right scaffold for the proximal tibials. They can deal with recoil, they can deal with dissection, they could deal with recalcitrant lesions, but they absorb with time, and you don't have that risk of having metal there or precluding you from a bypass or something in the future. Then more distal disease that goes down closer to the ankle, we're really hoping that these limus DCBs are successful or the right paclitaxel DCB comes out. I think that algorithm is going to look very different in the next five years and then that might creep back up into the above-the-knee space looking at bioabsorbable there, but I don't think we're at that point yet.

[Dr. Sabeen Dhand]
Well that's cool. Eric, I have a feeling we'll have you back on sooner than three to five years. That was really great, that's a lot of information we covered. Our big take-home point is drug-coated technology, drug-eluting technology works and really you should be using this in your treatment of peripheral vascular disease. It's obviously been shown in your coronary, you said you don't even have a bare metal stent on the shelf on the coronary.

[Dr. Eric Secemsky]
Exactly, exactly right.

[Dr. Sabeen Dhand]
Super great to have you on, any last words of wisdom, parting wisdom regarding this?

[Dr. Eric Secemsky]
Just first up thanks, Sabeen it's easy and fun to have a conversation with you, and BackTable has been just so successful of bringing these type of conversations to everyone. I really appreciate the opportunity to be on here. For the audience hopefully, if you haven't seen Sabeen or I on social media we're on there so reach out and if you have any questions please let us know. If I can just summarize, if you go to the Cook website you can find your way to the Zilver PTX Prediction Model. It's fun to play with. See if that fits into your algorithm. Take a look at the data.

It's really important to know the data in this space. Think about the anywhere from the over Zilver PTX trial IMPERIAL, EMINENT, and SPORTS which will be published soon. I think those are great foundational knowledge. You need to be in this space and hopefully, that will help drive your practice and that's what showed us the evidence. Again, thanks Sabeen, for allowing me to wax away on my feelings about drug-coated technology here and hopefully people find this interesting.

Podcast Contributors

Dr. Eric Secemsky

Dr. Eric A. Secemsky, MD, MSc, RPVI, FACC, FSCAI, FSVM is the Director of Vascular Intervention and an Interventional Cardiologist within the CardioVascular Institute at Beth Israel Deaconess Medical Center (BIDMC).

Dr. Sabeen Dhand

Dr. Sabeen Dhand is a practicing interventional radiologist with PIH Health in Los Angeles.

Cite This Podcast

BackTable, LLC (Producer). (2024, January 22). Ep. 407 – The Evolving Role of Drug Eluting Stents in PAD [Audio podcast]. Retrieved from https://www.backtable.com

Disclaimer: The Materials available on BackTable.com are for informational and educational purposes only and are not a substitute for the professional judgment of a healthcare professional in diagnosing and treating patients. The opinions expressed by participants of the BackTable Podcast belong solely to the participants, and do not necessarily reflect the views of BackTable.