An educational video: REALDES study: drug-eluting stent outcomes in PAD

Understanding long-term outcomes of drug-eluting stents (DES) is essential in treating peripheral arterial disease (PAD). In this educational video, Dr. Deloose presents findings from the REALDES study, a prospective, multicenter observational study comparing Zilver® PTX® and Eluvia® DES in real-world PAD treatment. DES selection was made at the physician’s discretion, without financial support or influence, providing an unbiased view of clinical practice.

The study evaluated the incidence of restenosis and target lesion patency over 36 months, with no statistically significant difference observed between Zilver PTX and Eluvia during the period.
Following the clinical presentation, Drs. Peña and McMackin provide expert commentary, discussing the implications of these findings for clinical decision-making, patient selection, and real-world treatment strategies. Their discussion places the data into practical contexts and helps translate the study results into practical application in PAD care.

Eluvia is a registered trademark of Boston Scientific Scimed, Inc.

Koen Deloose (00:11):
Hello, everybody. I’m Dr. Koen Deloose. I’m head of the department of vascular surgery in Sint-Blasius Hospital in Dendermonde in Belgium.

Koen Deloose (00:21):
And so, I’m very honored to present you last update on the REALDES study, and more particular the three-years data.

Koen Deloose (00:32):
What is the background actually of this study? Well, we all know that drug-eluting technology in general, and more particular drug-eluting stents, are significantly reducing the incidence of restenosis and reinterventions. And we know today we have on the market two drug-eluting stents: the Eluvia® of Boston Scientific and the Zilver® PTX® of Cook Medical.

Koen Deloose (00:57):
One is a polymer-based drug elution. The other is a non-polymeric-based drug elution. Drug: paclitaxel. On one side Eluvia with a low dose: 0.167 μg/mm².

Koen Deloose (01:15):
And then the 3 μg/mm² for the Zilver PTX. Both self-expandable stents.

Koen Deloose (01:24):
And so, actually, we know that there is a randomized— head-to-head randomized controlled trial, the IMPERIAL trial, with the two devices, with the Eluvia and the Zilver PTX. And I think we are all aware of the results over there, definitely after one year, where we’ve seen that there was a non-inferiority of the Eluvia standard setup of the study versus the Zilver PTX, with a 92.1% result after one year in the Eluvia group, and an 81.8% patency in the Zilver PTX group.

Koen Deloose (02:04):
But we notice that after two years— and this is an update that is published in Cardiovascular Interventional Radiology journal— so, seeing that the statistical significant difference is disappearing. And so, after two years we have an 83% efficacy in the Eluvia group versus 77.1% in the Zilver PTX.

Koen Deloose (02:28):
And then even when we are looking at five years, you see that— and in terms of TLR and in terms of primary patency and in terms of assisted primary patency, there is no difference at all anymore between both devices. That is one important remark concerning this randomized controlled trial. Beside this, we also know that a randomized controlled trial is also very particular, very well established in a very strict context, let’s say.

Koen Deloose (03:04):
And this is completely not comparable with what we are facing as interventionalists every day: the real-world setting. Here I give you some examples of the IMPERIAL study lesion characteristics.

Koen Deloose (03:17):
We are talking about lesions around 8, 8.5 cm. We are talking about reduced calcification. In 36%, there was no calcification. Moderate calcification in another third. And only in one third of the cases there was severe calcification. This is actually not my daily reality. The same for chronic total occlusions.

Koen Deloose (03:43):
Only in one third of the cases we were facing this, let’s say, complexity.

Koen Deloose (03:49):
Also, when we are looking at the patient characteristics, I was quite astonished to see that there was even 30% Rutherford 2 categorized patients, and the vast majority were Rutherford 3.

Koen Deloose (04:04):
So, also there, a lack of critical limb ischemia patients. And so, this was actually the background of setting up a real-world-data trial. And this was done in the REALDES study.

Koen Deloose (04:17):
So, Zilver PTX versus Eluvia in real, complex disease, with an update that I’m able to present to you today: three-years data.

Koen Deloose (04:29):
It is not really a randomized trial. It is a multicenter prospective observational study where the drug-eluting stent is chosen at the physician’s discretion.

Koen Deloose (04:41):
So, also an extensive prepping was mandatory in the protocol. And this is also a little bit different compared to the IMPERIAL trial and earlier trials.

Koen Deloose (04:53):
Restenosis was defined on duplex ultrasound with a PSVR cutoff of 2.4.

Koen Deloose (04:59):
And also, very important, there were no financial biases because the study was not financially supported by companies or whatever.

Koen Deloose (05:09):
So, here you see the follow-up of the REALDES study: 200 limbs, 184 patients enrolled. And at the end we’ve noticed that we had 86 patients in the Zilver PTX versus 98 in the Eluvia group.

Koen Deloose (05:23):
And at 36-months follow-up, we have 52 patients in the Zilver PTX group versus 47 in the Eluvia group. Here you see some characteristics, demographics, and comorbidities, and you see immediately that this is real-world data.

Koen Deloose (05:42):
Claudicants in two thirds of the cases, but one third of the cases, real CLTI patients. You see also that there is no statistical difference in terms of demographics and comorbidities between both groups. If we are looking at the lesion characteristics, also there you notice that quite an important amount of patients and lesions, they had a high PAC score.

Koen Deloose (06:09):
We are talking about also TASC C and D lesions in 60% of the cases, as you can notice. Pre-dilation was done in almost 100% of the cases in both groups. And post-dilatation also in all the patients. If we are looking at lesion length, again: 18, 16 cm. So, a little bit in favor of the Eluvia group: 16 cm cut, long lesions.

Koen Deloose (06:38):
If we are looking at total occlusions, more than half of the patients had a chronic total occlusion.

Koen Deloose (06:45):
When we are looking at the results in both groups in terms of primary patency, at three years you notice that there is no statistical difference of P value of 0.7 between both groups.

Koen Deloose (06:58):
82.5% in the Zilver PTX group at one year, 70% at three years. In the Eluvia group, respectively, 86% at one year and 65.2% at three years.

Koen Deloose (07:12):
The same for the freedom from TLR: at one year 88.9 for the Zilver PTX and 90.1 for the Eluvia. At three years 79.4% for the Zilver PTX and 76.3% for the Eluvia.

Koen Deloose (07:28):
Again, no statistical significant difference. If we are looking at a univariate analysis of the three-year risk on restenosis, we notice that there are no parameters, no variables significant. So also, the factors— Zilver PTX versus Eluvia didn’t show any difference at three years.

Koen Deloose (07:51):
An interesting finding in the REALDES study at 36 months was the difference in morphology restenosis. And so, here you see the difference between both groups. In the REALDES study, we’ve noticed that with the Zilver PTX we had reocclusions in 29.2% of the cases versus 70.8% cases with just restenosis.

Koen Deloose (08:16):
When we are comparing this in the Eluvia arm, we noticed that 57.7%— they had total reocclusions, versus restenosis in 42.3%.

Koen Deloose (08:31):
So, this was a very interesting finding. Was it surprising?

Koen Deloose (08:35):
I don’t think so, because if you are looking to more available data, for instance here in the CAPSICUM registry where we studied— where the Japanese people, they studied the Eluvia at one year, we noticed that there was are occlusion in 71.1% of the cases. 25.9% were stent thrombosis. And only in 28.9% we had restenotic disease.

Koen Deloose (09:03):
So, this is completely in line with the reocclusion rate that we found in the REALDES data. And the same for the Zilver PTX. We have also data available on this point in the ZEPHYR registry at one year, where we noticed that less than 25% had a class III, Tosaka III, instant reocclusion versus vast majority, 75%— they had more restenotic disease. So also, this is completely in line with the findings of the REALDES at three years.

Koen Deloose (09:42):
A clear explanation for this is, right at the moment, a question mark.

Koen Deloose (09:48):
Of course, we know the REALDES study has some limitations. It’s not really a real randomized design. There are confounding factors, there are selection biases, of course, but it gives a very clear trend in relation to these two drug-eluting stents.

Koen Deloose (10:06):
It’s a relatively small number, especially at the three-years follow-up.

Koen Deloose (10:10):
There are variations we’ve noticed during the procedural characteristics in vessel-prepping methods.

Koen Deloose (10:17):
So, also, this can influence results, of course. And last but not least, there was also not objective core lab check for the duplex ultrasounds or for the angiographies.

Koen Deloose (10:29):
Having said that, the take-home messages of the REALDES study—first of all, the ideal setting of a head-to-head randomized controlled IMPERIAL trial: Eluvia reached a statistical significant non-inferiority-powered better outcome at one year. But we noticed that from year two on up to year five, this difference disappeared completely. Equal results, Zilver PTX versus Eluvia. The real-life non-randomized prospective data from eight Japanese centers didn’t show any significant difference between the two devices.

Koen Deloose (11:05):
And this up to three years. There was a significant difference observed in terms of restenosis morphology, revealing an unexplainable higher incidence of total reocclusions with the Eluvia compared with the Zilver PTX.

Koen Deloose (11:21):
Thank you for your attention.

Koen Deloose (11:23):
So, I’m glad to be here with two colleagues, two friends, Dr. McMackin and Dr. Peña. And so, I’m very open to discuss with them these results, these findings, and also to hear their comments on this remarkable data at three years.

Constantino Peña (11:43):
I think this is a very interesting study. I appreciate your presentation of the data—very clear. And really looking at what is the long-term differences with two— what I think are two drug-eluting stents that we have available.

Constantino Peña (12:00):
I think, to me, looking at patency and clinical TLR rates: very similar after the first year, which has been in keeping with everything that we’ve seen from the IMPERIAL trial as well as in this patient population. What I think is interesting is, like you said, this is more real-world data, longer lesions, more occlusions, more patients with CLTI. And I think even in this patient population we see similar findings.

Constantino Peña (12:31):
To me, that is my first take-home message that I think is very important.

Constantino Peña (12:36):
The second point is the morphological differences in terms of failure rate. And what does this mean? I am not sure. I agree with you that I don’t know and can hypothesize why this is occurring in terms of reocclusions versus restenosis. Our concern is restenosis is easier to treat in terms of—compared to—reocclusions.

Constantino Peña (12:58):
But really why is this occurring? Is it clinically relevant? I think that’s something we need to continue to look at.

Katherine McMackin (13:04):
I agree with that completely and, you know, it was extremely well presented. I love the idea of real-world data, because when you first go into the operating room you want to think, “Am I making a safe choice for my patients?” And it’s nice to go in with this equipoise between the two stents going out to three years, because not everybody has access to both. So, regardless of your access, you know that that is a safe choice in terms of some of these key indicators: your primary patency, your target vessel, restenosis.

Katherine McMackin (13:32):
So, you know, I do love that idea that it’s equal within both.

Katherine McMackin (13:37):
The second thing is—everyone’s mentioning—is that long-term reocclusion versus restenosis. And you may made the good point of once you get out into that three-year-old data, we’re talking about a very small end. We’re in the 14–16 patient range. So, it is something to watch and something to look for. It’s not something that would currently change my practice, but it’s nice as we get into these real-world megadata access databases: Oh, this is something we want to look at, this is something we want to follow.

Katherine McMackin (14:03):
Is this going to play out 5, 10, 15 years, that this trend is going to continue?

Koen Deloose (14:10):
Thank you very much for your comments, and I can only agree. First of all, I think we all three— we agree that we need longer data. With one-year data—

Koen Deloose (14:23):
I think we are looking also from a health-economical perspective. Our healthcare providers, payers, whoever, they are not interested in one-year data. They are mainly interested in durability on the longer run. Of course, also our patients. I mean there are papers, scientific papers, that— One thing related directly to quality of life is the reintervention rate.

Koen Deloose (14:46):
And so, data at one year is really not— We want to see data at two, three, four, five years and these—

Koen Deloose (14:55):
I’m a vascular surgeon.

Koen Deloose (14:58):
It was always the comment that I got from the more open-oriented vascular surgeons, that, “You guys, endovascular specialists, you are looking at one year, maximum two years.” But now— I’m very happy now to speak about three-, four-, and five-years data. I think this is really important and especially looking at the TLR or the reintervention rate.

Koen Deloose (15:20):
I’m extremely interested also in this morphology of the restenotic pattern, because like Dr. Peña mentioned, we are living a little bit in the spirit, when you go to international congresses, of leaving nothing behind. We all know in this complexity of lesions—calcified, long lesions—CTOs, CLTI patients, that this remains a dream, at least in Belgium. I always ending up with some scaffolding, at least. And the comment that the, let’s say, the enthusiasts of leaving nothing behind are mentioning is, “Yeah, but if you have reocclusions afterwards, it is so difficult to re-treat.”

Koen Deloose (16:03):
Well, I think if we have these findings, and we see that there are two devices where potentially, and probably we need to see it in more reliable data, but where one device is creating more total or reocclusions, instant reocclusions, than the other one. Yeah, that’s for me at least an important argument to think about when I need to make the selection.

Constantino Peña (16:33):
I think you bring up a great point, and that is, really, as we start looking at our algorithm for treatment in the superficial femoral artery and we’re looking at real-world lesions, calcified lesions, long lesions, where does drug-eluting stenting fit in? And I think this data gives us some holistic view in terms of—that we have these stents available, what the results are so far, even though small numbers, to three to five years. But I think you’re exactly right.

Constantino Peña (16:58):
If you’re looking at restenosis versus reocclusions, is that going to affect our algorithm when you’re then competing against, again, leaving nothing behind? It’s always the balance, long lesions with our calcified—that you need scaffolds, and then, okay, how is it going to look?

Constantino Peña (17:16):
What am I going to do to that patient in four or five years, and am I going to be in a better situation or a worse situation? So, I think you’re exactly right, and I like the way you phrase that, and I agree with you on that— those— really important clinical impact of this type of data.

Katherine McMackin (17:29):
Yeah, because it is that balance of thinking 3, 5, 10 years ahead. But we want help with that interoperative decision making. It’s the choices we’re making now that are going to affect our patients 5, 10 years down the line.

Katherine McMackin (17:41):
So, all of those pieces that you mentioned about vessel prep. Is that really the underlying thing that’s setting us up for success long term? And I think the allusion in this paper that that may have importance is something that we can definitely look at going forward to see, okay, is that the piece that we’re missing that we really should be focusing on?

Constantino Peña (17:59):
How does this affect care in Europe in terms of the role of drug-eluting stents in Europe with this type of data?

Koen Deloose (18:08):
Well, actually, these data are quite new, they are quite recently published, presented, this three-year data.

Koen Deloose (18:17):
But I see more and more people at least concerned about this data in terms of a higher rate of instant rethrombosis, reocclusion, because we know that this is not so easy to treat.

Koen Deloose (18:35):
And then of course you also have the full story also supported by the CAPSICUM registry of the so-called—or positive remodeling or pseudoaneurysm formation and whatever.

Koen Deloose (18:49):
And so, where we left completely the tragedy, the Greek tragedy of the mortality problem with the paclitaxel, I see a little bit shifting towards more the issue of local toxicity of paclitaxel. And so, the combination of these findings—on one side CAPSICUM, some more trials, this pseudoaneurysm formation, on the other side probably a higher rate of instant rethrombosis and reocclusion.

Koen Deloose (19:22):
Some physicians, step by step, are thinking about it and potentially changing their mind. So, having said that, I think that we all agree that we need more long-term data, that we need more real-life, real-world data to confirm or at least to subanalyze the findings of the REALDES study.

Koen Deloose (19:49):
I would like to thank tremendously my co-panelists, Dr. Peña, Dr. McMackin, for this nice discussion, and hope to see you very soon.

Drs. Peña, McMackin, and Deloose are paid consultants of Cook Medical.