An educational video: ZilverPass trial: results and real-world impact

Clinical evidence plays a vital role in advancing the treatment of peripheral arterial disease (PAD). In this educational video, Dr. Deloose presents the five-year results of the ZilverPass study, a prospective, randomized, multicenter, non-inferiority trial comparing endovascular therapy using the Zilver® PTX® drug-eluting stent to prosthetic bypass surgery for the treatment of femoropopliteal lesions.
The presentation reviews key study outcomes, including procedural characteristics and longer-term results. Findings demonstrated a statistically significant reduction in complication rates, as well as shorter procedural time and hospital stay, in patients treated with Zilver PTX compared to bypass surgery.

Following the clinical overview, Dr. Peña and Dr. McMackin join the discussion to offer their expertise on how the ZilverPass results align with clinical practice and their own professional experiences in treating patients with PAD. Their conversation places the trial data in actual clinical context, emphasizing how a clearer understanding of the evidence informs treatment considerations and actual decision-making.
This video is designed to support education and awareness by presenting clinical data in a structured, accessible format for learners, healthcare professionals, and others seeking to better understand PAD treatment options.

Koen Deloose (00:12):
Hello, everybody. I’m Koen Deloose. I’m a vascular surgeon, head of the department of vascular surgery, in the Sint-Blasius Hospital in Dendermonde, in Belgium. And I have the pleasure and the honor to present you today the final five-year results in the ZilverPass study. So, what is the objective of the study?

Koen Deloose (00:35)
It’s to evaluate performance of the Cook Zilver® PTX® paclitaxel-eluting stent compared to prosthetic bypass surgery for the treatment of above-the-knee femoropopliteal TASC C and D lesions and evaluating them with the same assessment methods.

Koen Deloose (00:53):
It is a prospective, randomized, non-inferiority, multicenter study where we randomized 220 patients in a one-to-one way in four countries and 13 clinical centers. Like I’ve mentioned, on one group, the Zilver PTX, versus the other group, prosthetic bypass surgery. So, no venous bypass surgery above the knee.

Koen Deloose (01:18):
Primary endpoint of the study, first of all, is very clear: primary patency at one year. And this is quite important. We know that if we have endovascular studies, we are always looking at the absence of binary restenosis or occlusion within the treated lesion.

Koen Deloose (01:37):
And we do this very objective with color-flow duplex ultrasound PSVR measurements with a cutoff of 2.3, 2.4 here in our case, without TLR, at one year.

Koen Deloose (01:49):
In the bypass surgery literature, sometimes this is a little bit different analyzed. It is mostly based on the Rutherford AM criteria published years ago in the Journal of Vascular Surgery. And, actually, this is more like an open or a closed bypass, a patent or a non-patent bypass, but not so objective as measured on color-flow duplex ultrasound. Well, in this ZilverPass study, we are also analyzing the bypass results based on binary restenosis at the proximal distal anastomosis over the entire length of the bypass with the same PSVR cutoff of 2.4, and also without clinical-driven reintervention to restore the flow in the bypass. Here you see the timeline of the study, and today I’m very happy to present you the final five-year results. In an exclusion criteria: very straightforward. Only Rutherford 2–5 patients were enrolled, stenotic or reocclusive lesions, de novo lesions in the fem-pop area, and a minimum of 15 cm in total lesion length was required. Exclusion: any previous surgery or endovascular procedure in the target vessel—so a primary treatment—perioperative unsuccessful dilatation or treatment of the inflow is quite an exclusion criteria, quite logical.

Koen Deloose (03:24):
Any other planned surgical intervention or procedure within 30 days of the procedure was not allowed, and major distal amputations in the study or the non-study limb were excluded.

Koen Deloose (03:39):
If we are looking at the patient demographics of this RCT, you notice immediately that there is some difference at one point—a statistical significant difference. And this is in the Rutherford categorization, where we have actually, let’s say, in claudicants in the Zilver PTX group, 70% versus 30% CLTI patients versus the bypass group, we have more CLTI patients, 44% or 45% versus 55% in claudicants in the bypass group. So, this is an important difference in terms of patient demographics.

Koen Deloose (04:23):
Having said that, when we are looking at a lot of risk factors, smoking history, diabetes, coronary disease, cardiovascular disease, renal insufficiency, and so on, there were no statistical differences between both groups. But if we are looking at hypertension, obesity, and hypercholesterolemia, we notice that there was a significantly higher amount of patients with these risk factors in the bypass group compared to the Zilver PTX group. So, a slightly more diseased population in the bypass cohort. Very complex lesions: I already mentioned, according to the protocol, at least 15 cm.

Koen Deloose (05:06):
Well, here we notice that finally we ended up with a mean lesion length of 25 cm in both cohorts and a chronic total occlusion rate of 95%. I don’t think there are a lot of clinical studies available today with this lesion characteristics in both cohorts.

Koen Deloose (05:28):
When we are looking at the procedural characteristics, we notice there two quite important differences also in terms of health-economical analysis. We notice that the procedural time in the endo group was almost half of the time compared to the open surgery group, quite logical. And also, if we are looking at hospital stay, a quite important economical factor, we notice that the mean hospital stay was 2.5 days, actually quite high, and it’s not the case anymore today in the endo group, versus 8 days in the bypass group. So also there, quite important statistical significant difference.

Koen Deloose (06:12):
If we are looking at the freedom from complications at 30 days, a safety endpoint, we notice that we had 95.6% in the endo group versus 88.7% in the bypass group. Also, this I think is not surprising, that we have a statistical significant difference between both groups.

Koen Deloose (06:34):
In the bypass group, wound infections, most of them superficial, but also some deep wound infections—there were lymph fistulas, lymphedema, and so on. And in the endo group there were only a few puncture-site hematomas or post-procedural bleedings.

Koen Deloose (06:52):
If we are looking at the survival rate— And when we were collecting the data, quite important, because we were confronted with the paclitaxel issue with the Greek publication, the meta-analysis.

Koen Deloose (07:16):
But here, according to this also, no relevant findings. Exactly the same survival rate at five years between the Zilver PTX group, 69.10%, and in the bypass group, not paclitaxel based, 71%. And there all the causes of that are summarized. Important, primary patency at five years, if you notice this: Zilver PTX, 49.3%, versus the bypass, 40.7%. No statistical significant difference between both groups at five year with the same assessment methods.

Koen Deloose (07:52):
So, as I’ve mentioned in the beginning, very important—PSVR-based cutoff: 2.4 for both groups.

Koen Deloose (08:00):
Freedom from TLR at five years: 63.8%. And this is for me an amazing result. It means that more than 6 out of 10 didn’t have any reintervention after five years of their primary treatment. So, this is amazing.

Koen Deloose (08:18):
And 52.8% in the bypass group—freedom from TLR at five year—no difference between both groups.

Koen Deloose (08:26):
Also, in terms of the clinical assessment—so the Rutherford evaluation—you notice that the results in between both groups are quite consistent and persistent over the years. So, up to five years we notice that the vast majority is a Rutherford 0 or 1—maximum 2—in both groups.

Koen Deloose (08:50):
So, the take-home messages of this final update of the ZilverPass study with the Zilver PTX versus prosthetic bypass shows us amazing results in challenging lesions: mean lesion length of 25 cm; 95% CTOs; primary patency based on objective measurements by duplex ultrasound: 49.3% at five years; and a freedom from TLR of 63.8% in the Zilver PTX group. No statistical significant difference with the prosthetic bypass group. There was a significant reduction of complication rate, shorter procedural time, shorter hospital stay in the endo group—not surprisingly—and there was also a consistent positive clinical status over five years in a very diseased population. And I think these data are looking quite promising.

Koen Deloose (09:49):
I thank you for your attention, and I’m happy to discuss with my good colleagues and friends, Dr. McMackin and Dr. Peña, to listen to their comments, to their questions, to their remarks and points of disagreement in this fantastic ZilverPass study.

Katherine McMackin (10:10):
Thank you so much for that wonderful overview going over this study. This study touches on all of the pieces that I think about when you’re deciding, do you want to do an endovascular option or a surgical option? What is the best thing for your patient?

Katherine McMackin (10:23):
And you touched on so many of them. These are long lesions, even longer in the study than what they initially thought it was going to be. It’s very, very diseased. It’s completely calcified. It’s completely occluded. Those risks that were always weighing, they all came up: It was access complications, it was infection of the prosthetic bypasses, there’s patients who are obese. Those are the real-world patients that we’re dealing with every day.

Katherine McMackin (10:46):
I think for me, the one surprising thing that goes against sort of that common teaching is the reinterventions. And you think, “Oh, if you’re going to do endo, they’re coming back over and over again.” But the primary patency’s the same. Those reinterventions were actually less for the TLR.

Katherine McMackin (11:02):
So that’s the part that surprised me going through this study.

Constantino Peña (11:07):
Yeah, I agree with that. And I was, I think, very surprised when you saw the five-year data comes from the ZilverPass study.

Constantino Peña (11:15):
I think when you’re making a decision on a long SFA lesion, you always consider surgery. And I think we have to ask the question, if this was a vein graft, would it be different? And I think I’ll pass that back to you in a few seconds. But I think when you’re looking at a prosthetic versus a long segment stenting of the SFA, this data is actually— tells us a lot, I think. It gives us that thought that maybe this is a viable option in these patients, particularly in patients with CLTI, particularly in patients that we know already have a lot of comorbidities and effects of their mortality. And this may be, I think— Is this an equal option of bypass versus long metal stenting? And I think there you can start making your decision with a Zilver PTX stent.

Koen Deloose (12:07):
I cannot agree more with both of you. According to the question or the point concerning the vein or a prosthesis, we had long discussions on this with the investigators, with the committee, with the sponsor, and so on. And we absolutely— The rationale of the study was to stay as close as possible to the reality, to the daily reality. And the patient population, as you mentioned, is a clear proof of this.

Koen Deloose (12:38):
And then we had a look while making these discussions: Okay, but also if we stay close in our patient population, close to reality, we also need to do this in our treatment modality. And we all relooked the 13 participating centers, we relooked at our daily vascular surgery, let’s say, habits and situations, and in Dendermonde, but also in the majority of the other centers, when we are talking for above-the-knee bypass, we are using, quite often, in the majority of the cases, prosthesis. And we try to save the vein for the next stage, for the below-the-knee bypasses, for the fem-distal bypasses.

Koen Deloose (13:27):
That was one important point. There are also some papers available in Journal of Vascular Surgery, for instance, where if you are using— And I’ve mentioned, it’s not that clear, but the majority of the bypasses, the prostheses, that were used here were the quite modern ePTFE heparin-coated bypasses. And there the results to an available vein are quite close, especially in above-the-knee settings in terms of durability, patency, and so on. So, that was actually the reason that we opted in this particular study for prosthesis rather than for the vein, because it was the closest to our daily practice for above-the-knee treatment.

Katherine McMackin (14:13):
And that’s something where our practices is similar in the US: We have that same “failing forward” idea where if we can save the vein for that long distal bypass instead of using it for the above-knee pop, we’ll mostly use those heparin-bonded grafts for our fem above-knee pop as well here.

Koen Deloose (14:30):
Yeah, yeah, I totally agree. One thing that we need to discuss also, quite open: What I regret a little bit in the study is the fact that—that’s a comment that we also get quite often as investigators— that it seems— although it was perfectly by-computer, head-to-head randomized, that it seems that the bypass group has quite a more diseased population based on these significant risk factors, differences, and also based on the CLTI core. So, probably there a stratification is probably the solution.

Koen Deloose (15:14):
Today, I’m running another randomized controlled trial for the common femoral artery where we are comparing an endo approach versus an open approach. And with my experience in this ZilverPass study, I did a stratification process in advance, so to be 100% sure that at the time of the randomization that we have equal cohorts and in the open and in the endo groups. What do you think about this?

Constantino Peña (15:43):
I think that’s very important, because I think as we start looking at this data and how it’s going to affect practice, I think that’s the kind of questions people will always ask and question, right? I feel that this type of study, this result of the study, went against our dogma, what we believed in.

Constantino Peña (16:03):
And I think because of that, it’s going to take a little bit more to move the needle and change practice. When I see this, I think it’s important to say, in the right patient, it is that you need to go and place a scaffold in a significant length in the SFA. It is comparable to surgery with a prosthetic. And I think how to make sure that our operators feel that and understand that and think that this is true is kind of going to be our challenge going forward.

Constantino Peña (16:31):
Because I really think this really, like I said— It’s a study that has changed what we previously thought of, and that’s from the endovascular and surgical community. And I think it’s something that is great, because as you see this, it’s that necessary data that we need to move forward. And it’s going to be interesting to see how the practice will then change over the next years and decade.

Katherine McMackin (16:52):
Yeah. And as you look at these studies going forward, I think that difference in CLTI, someone sees that and immediately thinks, “Oh, well, we’re talking about different outflow.” So, whether that’s not just looking at lesion length, but we’re talking about following all of these outflows, whether that be GLASS scoring or some other scoring system, so we know, are we really talking about we’re putting a stent in a same-length lesion? But what are we talking about downstream that’s going to affect our patency, affect our need for any intervention? So, I think that’s going to be, going forward, things we’ll include in further studies.

Koen Deloose (17:22):
Yeah. I think very good remark, Katherine. So final question for you: Knowing these data right at the moment, you are a vascular surgeon, so you can offer also—like in my case—you can offer both treatment modalities yourself.

Koen Deloose (17:40):
Based on these results, if you have a patient in front of you, which kind of parameters will define one or the other decision, open or endo approach first? Very open.

Katherine McMackin (17:56):
So, it definitely takes into all of those other pieces that go into it that come up in this study. Obesity is one of the biggest ones. Am I worried about the infection risk? Does that risk go up? Am I worried about surgery time, an hour versus an hour and a half? Probably not. But a long hospital stay can definitely put an effect on somebody.

Katherine McMackin (18:13):
So, for a claudicant, I think that endo approach first makes perfect sense. I think when you get a little bit more nuances, when you get to the CLTI patients— and you still may have that endo option first, but that’s when you really start to try to parse it out. What do I need to be doing first to get them more flow right now?

Koen Deloose (18:28):
Thank you very much for this wonderful comment. So, I think I can summarize this session. I mean, the ZilverPass five-year results are showing— is actually one of the first head-to-head randomized trials, open surgery versus Zilver PTX endovascular treatment, assessed with the same assessment methods and showing at the end no statistical difference between both groups except for hospital stay, for procedural time, and complication rate.

Koen Deloose (19:03):
I would like to thank Tino and Katherine for your wonderful comments and I wish you a great day.

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