Latest / European Society for Vascular Surgery / Drug eluting technology: is it dangerous and does it even work? A look at the timeline of evidence with Professors Behrendt and Roy

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Drug eluting technology: is it dangerous and does it even work? A look at the timeline of evidence with Professors Behrendt and Roy · European Society for Vascular Surgery

• 0:12
  Hello and welcome to the ESVS podcast. We are
• 0:14
  recording live here at the annual meeting in
• 0:16
  Belgrade, Serbia. I am Laurence Bertrand. And I'm
• 0:19
  Safa Riahi. And today we are discussing drug -eluting
• 0:22
  technology. We're taking a focused look at the
• 0:24
  most impactful literature in this field, taking
• 0:27
  a chronological look at where the evidence has
• 0:29
  taken us and where the discussion stands today.
• 0:32
  We're pleased to welcome two experts in the field,
• 0:34
  Professors Joy Roy and Christian Behrendt, to
• 0:36
  the podcast today. Professor Roy is a consultant
• 0:39
  vascular surgery local expert on drug -eluting
• 0:41
  stents at the Karolinska Institute, Sweden. And
• 0:44
  Professor Behrendt is the medical director of
• 0:46
  the German Institute for Vascular Medical Health
• 0:48
  Research, also known as the DIGG, as well as
• 0:51
  head of the department vascular surgery at the
• 0:53
  Askleiposklinik, Wandsbeck, Germany. Welcome
• 0:55
  to you both. Thank you. It's a pleasure to be
• 0:58
  here. Thank you very much. Nice to be invited.
• 1:00
  Before we get into the literature, let's very
• 1:02
  briefly level set for some of our trainees listening
• 1:05
  in. When we talk about drug diluted stents in
• 1:08
  PID, we're primarily referring to stents coped
• 1:10
  with paclitaxel, a cytotoxic agent that enables
• 1:13
  smooth cell proliferation and therefore aims
• 1:16
  to reduce neoantimal hyperplasia and dristinosis.
• 1:19
  Dragolutin balloons and stent were developed
• 1:21
  to address the high -risk stenosis rates seen
• 1:23
  after playing angioplasty and bare -metal stenting
• 1:25
  in fem -pop diseases, and early trials showed
• 1:28
  impressive improvements in patency and reduced
• 1:30
  need for re -intervention. Professor Roy, could
• 1:34
  you take us back to the beginning of the initial
• 1:36
  packet XL story? What initial evidence did this
• 1:39
  technology rest on allowing it to become so widespread,
• 1:42
  and how much of the evidence was borrowed from
• 1:44
  cardiology and coronary stenting at the beginning
• 1:47
  of this story? Thank you. So for me, this story
• 1:51
  began around the year 2000 when I was still a
• 1:55
  PhD student, finished my PhD, and it was the
• 1:58
  European Society of Cardiology meeting in Stockholm.
• 2:01
  And that was the first time I heard about it
• 2:03
  when Patrick Sorois, a cardiologist, he published
• 2:07
  the first study on drug eluting technology in
• 2:11
  PCI and showed that there was zero risk of stenosis
• 2:13
  using drug eluting technology. They used rapamycin,
• 2:18
  now also called serolimus, on these plaques.
• 2:23
  So that was really revolutionary, and everybody
• 2:25
  was talking about it. So it was very cardiology
• 2:30
  borrowed, not very much peripheral. But then
• 2:33
  after a year or so, there were coming some data
• 2:37
  that patients were dying after this, when they
• 2:42
  had received drug -eluting stents. And what happened
• 2:45
  was that it turned out that the drugs did not
• 2:50
  only inhibit proliferation of smooth muscle cells,
• 2:54
  but it also inhibited proliferation of the endothelium.
• 2:58
  So once they stopped the DAPT, they got thrombosis.
• 3:01
  And in cardiacs, if you get a... then you get
• 3:07
  a myocardial infarction. So that was all from
• 3:10
  cardiology. In the peripheral field, then the
• 3:13
  first studies came around 2004, and they were
• 3:16
  from Germany, from your country, Gunatepe. I
• 3:21
  remember he published the THUNDER trial and the
• 3:23
  FEMPAC, and then later came the IMPACT trials.
• 3:26
  So those were in the peripheral field, and they
• 3:29
  used more paclitaxel. And the reason being that
• 3:35
  the earlier studies on sirolimus did not show
• 3:39
  any effect on the peripheral side, probably because
• 3:43
  sirolimus is really slowly absorbed in cells.
• 3:47
  So as we said in the introduction, we're going
• 3:49
  to try and follow this data a little bit chronologically,
• 3:51
  especially also for trainees listening who haven't
• 3:54
  had the benefit of following the story from the
• 3:56
  beginning or falling into this now. Since then,
• 3:59
  there's been somewhat of a roller coaster of
• 4:01
  evidence proving and disproving the effectiveness
• 4:03
  of drug -eluting technology in the PAD setting,
• 4:07
  and also some evidence surrounding the dangers
• 4:09
  of Paclitaxel. Most famously, there was a systematic
• 4:12
  review by... written by Katsanos et al. and published
• 4:15
  in the Journal of American Heart Association
• 4:17
  in 2018. Using data from 28 randomized controlled
• 4:21
  trials, Katsanos concluded that while Paclitaxel
• 4:25
  devices were safe at one year, they were linked
• 4:27
  to an increased risk of all -time mortality at
• 4:29
  two years, risk ratio of 1 .68. and even more
• 4:33
  so at five years, a risk ratio of 1 .93. Compared
• 4:36
  to uncoated devices, they also pointed out a
• 4:39
  potential dose -response relationship showing
• 4:41
  an excess of risk of death per milligram year
• 4:44
  of paclitaxel exposure. Professor Behrendt, can
• 4:49
  you tell our listeners a little bit about what
• 4:51
  is now in retrospect known as the Katsanus pause,
• 4:53
  where this data led to FDA warning and a temporary
• 4:57
  pause of the use of this technology in many places
• 4:59
  around the world? Yeah, first of all, I think
• 5:03
  it's not just that Konstantinos Katsanos published
• 5:07
  a meta -analysis, but also the fact that immediately
• 5:11
  after this publication, there were some issues
• 5:16
  with data presentation and data publication in
• 5:20
  the original articles. And this led to a mistrust.
• 5:29
  immediately and in such a situation there is
• 5:32
  no other option than halting everything asking
• 5:38
  what happened looking at the data and i think
• 5:41
  the fda and other regulators have done the right
• 5:45
  thing because do not harm first that's the the
• 5:50
  basic basic rule and i think it's it's not just
• 5:55
  the results that were published by Konstantinos
• 5:58
  Katsanos. But to get back to that, before this
• 6:02
  paper, this first paper was published in Jaha,
• 6:06
  there was, at least in countries like Germany,
• 6:10
  and we are known as a very decentralized, large
• 6:13
  healthcare system with a lot of hospitals involved,
• 6:17
  especially in the endovascular treatment of people
• 6:20
  with PAD, there was a widespread use. of Perclitaxel
• 6:24
  -based strategies. In some, I would say 30 to
• 6:30
  50 % of all procedures were done with such devices.
• 6:34
  So there was a widespread. And if you look at
• 6:38
  the data, the hospital -based data, the quality
• 6:42
  reports in Germany, for instance, this was not
• 6:45
  treatment reality in all hospitals. It was mainly...
• 6:52
  due to the high volume centers also involved
• 6:57
  in the trials, so to say. And I'm not really
• 7:02
  sure if after that happened and the FDA and the
• 7:07
  German regulators and the European regulators
• 7:09
  issued a warning. that there was really a Katsanos
• 7:13
  pause. There was, however, a stop of enrolling
• 7:16
  trials. Of course, I mean, the SweetPet program,
• 7:20
  I don't know how long, but they halted the recruitment
• 7:23
  joy for a month at least or a year or so. Over
• 7:28
  a year. Over a year, yeah. So there was an impact,
• 7:31
  but if this is really a Katsanos pause, I'm not
• 7:34
  that sure. But after the FDA, that was the leading,
• 7:41
  regular regulation agency worldwide used all
• 7:45
  the observational data and conducted own meta
• 7:51
  -analysis discussed with all the experts of all
• 7:54
  sides they have withdrawn the initial warning
• 8:01
  And this led to a heterogeneous situation. FDA
• 8:06
  has no longer any warning issued. The European
• 8:10
  agencies have a different understanding. In Germany,
• 8:15
  the warning is still active. You know, that's
• 8:17
  the situation we have today, but I'm still not
• 8:19
  sure if that's a Katsanos pause. Thank you for
• 8:22
  that. Dr. Joy, you talked a little bit about
• 8:24
  this just now in terms of the dangers and how
• 8:27
  that pathophysiologically would make sense. makes
• 8:30
  sense in the cardiology setting, but what about
• 8:33
  in PAD? In terms of pathophysiology, is there
• 8:36
  logically a good reason to fear the dangers of
• 8:40
  Paclitaxel? Why might it make sense that there
• 8:42
  may be hidden dangers? So, yeah, just to disappoint
• 8:45
  you, I cannot give you an answer for that. I
• 8:47
  wish I knew. It's really hard to say what the
• 8:50
  mechanism could be. We know that from Paclitaxel,
• 8:54
  there's a lot of distal embolization, or at least
• 8:56
  there is distal embolization into the muscle
• 8:59
  arteries and stuff. But does it go into the heart?
• 9:02
  Does it affect that? That has not been shown.
• 9:05
  So it's still hard to disregard the Katsanos
• 9:08
  trial and then the Sweetpad trial that we'll
• 9:11
  be talking about. Yeah, we're coming up to that,
• 9:13
  yeah. So we don't know. What I often hear and
• 9:17
  what people say... that Paclitaxel cannot be
• 9:20
  dangerous because it's been given to patients
• 9:22
  with different cancers, I think that's a wrong
• 9:27
  reasoning because I think there is such a great
• 9:30
  benefit in cancer. Right. So that takes away
• 9:34
  the small risk there maybe. You wouldn't find
• 9:35
  the risk in those groups. There's too much of
• 9:38
  a bias in the selection in those groups. Yeah.
• 9:40
  That makes sense. Thank you, Professor Roy. Maybe
• 9:43
  the field needs more translational data to answer
• 9:46
  this question. And since the Katzenos scare,
• 9:50
  there has been a wave of evidence disproving
• 9:53
  the claim dangers. Professor Berrand, you have
• 9:56
  been intimately involved in one of the most meaningful
• 9:58
  German registry papers and the movement against
• 10:00
  this. Can you tell us a bit about this evidence?
• 10:04
  Actually, we published three large health insurance
• 10:07
  claims data analysis on the topic. The first
• 10:10
  one was used for the FDA decision. In sum, I
• 10:19
  don't think there was any mortality signal in
• 10:22
  real -world evidence. I don't believe in it.
• 10:25
  I don't think this is really a signal that was
• 10:28
  in the observational data, at least not the observational
• 10:31
  data that I was analyzing with my team. We did
• 10:36
  some research because I'm a registry nerd and
• 10:40
  I am examining, determining residual confounding.
• 10:44
  There is residual confounding in underpowered,
• 10:47
  poorly designed, randomized controlled trials,
• 10:49
  as well as in observation research. And we use
• 10:53
  some methods to adjust for residual confounding,
• 10:57
  but you can't get rid of that problem. I think
• 11:00
  the problem is, the underlying problem is, that
• 11:04
  we actually had a mortality difference and that
• 11:12
  the vast majority of the signal we could measure
• 11:16
  was in female patients with femoral popliteal
• 11:22
  artery treatment. And there was an underlying
• 11:26
  confounding or an impact of statin treatment.
• 11:30
  And this, the optimal pharmacological treatment,
• 11:33
  as well as best medical treatment, is really
• 11:36
  poorly collected by randomized trials, especially
• 11:39
  in, I have to say, industry -sponsored, smaller
• 11:43
  pilot trials and underpowered trials. you have
• 11:47
  to check for these confounders and then you have
• 11:50
  to design the randomized control tries appropriately
• 11:54
  to adjust for that. But I think this was the
• 11:59
  problem. Another thing is that there were some
• 12:02
  changes in the interpretation of the meta -analysis
• 12:06
  that were published afterwards when Gazzanos
• 12:10
  published the first meta -analysis. And this
• 12:12
  was also due to the... completing data they they
• 12:16
  added follow -up data yeah they changed the base
• 12:19
  subsequent yeah they changed it so you see how
• 12:23
  easy it is to to change a signal if you yeah
• 12:28
  modify the analysis if you add or remove some
• 12:33
  data or edit some variables that's all um highlighting
• 12:39
  the fragility of signals if you don't have a
• 12:42
  well -designed randomized control trial. Despite
• 12:45
  large numbers, in fact. Thank you, Professor
• 12:47
  Berland. It's striking how differently population
• 12:50
  -based data and meta -analysis trials can answer
• 12:53
  the same question. Now, staying with the evidence
• 12:56
  that helped turn the tide, Dr. Roy, in your opinion,
• 13:00
  what other evidence was key in ending the Casanova's
• 13:02
  pause? Some are keen to clue the imperial trial.
• 13:05
  Can you tell us more about that? So, yeah, just
• 13:08
  to continue on that line. So I think the industry
• 13:10
  felt very strongly against the Katsanos trial.
• 13:12
  And of course, for us as interventionists and
• 13:14
  doctors, we were really worried that we'd put
• 13:18
  our patients at risk. And I think the Imperial
• 13:22
  trial that you're talking about, as I know it,
• 13:26
  it was a trial, a randomized trial that compared
• 13:30
  the silver PTX. polymer -free stent compared
• 13:35
  to the Illuvia, which was a polymer -coated stent.
• 13:37
  And they did comparable results in the FEMPOC
• 13:40
  segment for five years. So I think really that
• 13:43
  did not help in ending the Katsanos pause. For
• 13:47
  us, but there were quite a lot of observational
• 13:50
  trials that did not show any statistical differences
• 13:53
  in mortality. But perhaps for us, the main study
• 13:58
  was that the SWEDPAD investigators, they had
• 14:00
  suspended their trial. And they went through
• 14:03
  an interim analysis, and the paper was published
• 14:06
  in the New England Journal in 2020, where they
• 14:09
  did not see any difference in mortality between
• 14:11
  the groups. And that, at least in Sweden, it
• 14:15
  was the basis for the Ethical Review Authority
• 14:17
  to allow the trial to continue. Just to touch
• 14:20
  base on the trial, it was the long -term follow
• 14:24
  -up that showed absolutely no evidence of increased
• 14:26
  mortality signal. It served as maybe a pillar
• 14:30
  of safety data that gave clinicians and regulatory
• 14:32
  bodies the confidence to keep packet XL coated
• 14:35
  devices on the market. So the Imperial Trail
• 14:38
  was a randomized study between two drug technologies,
• 14:43
  right? So the mortality difference was comparing
• 14:46
  to some, that was not part of the study. Yeah.
• 14:51
  So that was just an extrapolation of the data.
• 14:54
  Yeah. Yeah. So the real study was just between.
• 14:57
  between two drug -eluting devices. You're saying
• 15:01
  there's not enough, like there wasn't a proper
• 15:02
  control group in that study. They're not controlling
• 15:05
  it with non -drug -eluting devices. Right, right.
• 15:08
  However, it is... So they compared it with historical
• 15:10
  data on mortality. Yeah, yeah, yeah. Fair enough.
• 15:13
  Good point. Absolutely. Now, in the next twist
• 15:16
  of the Katsenos controversy, we have a fresh
• 15:19
  systematic review written by Katsenos Yo on...
• 15:23
  choice piece in the European Journal of Vascular
• 15:25
  Endovascular Surgery, the June edition of the
• 15:27
  CEA 2026, again showing evidence of a potential
• 15:30
  harmful effect in all -cause mortality after
• 15:33
  using pachytextile devices. Dr. Berrin, for you,
• 15:37
  what was the take -home messages from the study,
• 15:40
  and will this bring on the next cutaneous pause?
• 15:43
  No, I don't think so. I think after all these
• 15:48
  heterogeneous meta -analysis there's nothing
• 15:51
  more and especially no evidence coming out of
• 15:54
  any new analysis for me the case is closed i
• 15:59
  don't believe in a mortality signal i think it
• 16:03
  was artificial and i think it was yeah due to
• 16:07
  data problems due to residual confounding due
• 16:11
  to missing data due to uh poorly designed randomized
• 16:15
  control trials and you know the old saying garbage
• 16:19
  in garbage out you you cannot get more out just
• 16:23
  because you redo analysis so for me it's an interesting
• 16:27
  paper it's a good conclusion but it doesn't reopen
• 16:31
  the issue for me but the whole discussion is
• 16:35
  not really about mortality excessive mortality
• 16:38
  anymore yeah Yeah, I mean, I think you're exactly
• 16:41
  right. And that's bringing us to the next thing.
• 16:42
  We're moving away now from the safety concern
• 16:45
  to the topic of actual effectiveness of this
• 16:48
  technology, right? Regulatory bodies at large
• 16:51
  currently accept the safety data and it remains
• 16:55
  on the market. But is it actually effective?
• 16:57
  What evidence do we have? Put simply, if we believe
• 16:59
  it doesn't hurt, does it actually help? Some
• 17:02
  of the most talked about data, we've mentioned
• 17:04
  it already, thank you, Dr. Joy, is from the SWEDVASC
• 17:08
  trials. These are two randomized control trials,
• 17:10
  one and two, using Swedish National Registry
• 17:13
  data to track patients. One is focused on chronic
• 17:17
  limb -threatening ischemia and two on intermittent...
• 17:20
  Dr. Joy, could you tell us a bit about these
• 17:22
  trials and summarize for us the main take -home
• 17:25
  messages of this data? I realize they're big
• 17:27
  trials and we could talk a whole hour only about
• 17:29
  this, but it's in the interest of contextualizing
• 17:32
  it for, you know, trainees who are trying to
• 17:35
  follow the story. Thank you. So the sweetpot
• 17:37
  trials were register -based randomized control
• 17:41
  trials, which is, at least we think it's a good
• 17:45
  thing to be able to run a randomized trial through
• 17:48
  a registry. It makes it easier to run. So we
• 17:51
  had two trials, SWITPAD1 and SWITPAD2, which
• 17:54
  were going on concurrently. So SWITPAD1 had 2
• 17:57
  ,355 patients. Primary endpoint was major amputations
• 18:02
  on that ipsilateral limb, yeah. And we did not
• 18:05
  see any difference between these two. And the
• 18:08
  secondary endpoint was with re -intervention
• 18:10
  rates, where there was a decrease in the re -intervention
• 18:13
  rate at one year, but not at five years. The
• 18:17
  SWITPAT -2 was a patient, we had 1 ,155 patients,
• 18:22
  and it was patients who had claudication. And
• 18:25
  the primary endpoint was the quality of life
• 18:27
  with the vascular questionnaire. And there, there
• 18:31
  was no difference. So interestingly there, the
• 18:34
  mortality signal became interesting there because
• 18:37
  at the end of the trial, at the median follow
• 18:39
  -up of 7 .1 years, there was no difference. But
• 18:41
  at five years, there was a significant difference
• 18:43
  with a hazard ratio of 1 .47. So this sort of
• 18:47
  started again some of the discussions. Thank
• 18:50
  you for that. To Bernd, you recently gave an
• 18:52
  interesting presentation talking about the SweetPad
• 18:54
  studies and other drug and new technology data
• 18:56
  in my home department in LMU in Munich. I'd like
• 19:01
  to ask you to bring some of that conversation
• 19:02
  here today and ask you to play devil's advocate
• 19:04
  for SweetPad. What are the main weaknesses of
• 19:06
  this study? Where are the problems in SweetPad?
• 19:09
  Well, that's a tricky question. You know, these
• 19:13
  are all design decisions. If you have a well
• 19:16
  -designed randomized control trial and you want
• 19:18
  to really just randomize one device against another
• 19:22
  device, you need a protocol, you need the protocol
• 19:25
  to be followed 100%, you need proper size, you
• 19:29
  need the follow -up call lab that really makes
• 19:33
  it impossible that the interventionalist, the
• 19:37
  physician, is taking part in differences. On
• 19:42
  the other hand, you have registries like Sweet
• 19:45
  Vask. You try to include all patients who underwent
• 19:49
  a certain treatment that comes along with pragmatic
• 19:54
  design decisions like you cannot be sure. that
• 19:59
  the follow -out outcome is really the same lesion
• 20:03
  to the best it may be the same vessel maybe or
• 20:06
  sometimes even just the same leg you don't really
• 20:09
  know is it like a restenosis or due to a restenosis
• 20:12
  or is it maybe an embolic occlusion that happened
• 20:17
  that led to an amputation you know that's you
• 20:21
  have to get rid of some information but instead
• 20:25
  you get more information so I don't want to point
• 20:31
  on weaknesses and strength of this study or all
• 20:35
  the randomized controlled trials. I think they
• 20:38
  all have pros and cons. But I think in terms
• 20:41
  of overall effectiveness with patient -related
• 20:45
  endpoints, this is a particular strength of...
• 20:49
  pragmatic trial, while having a core lab and
• 20:53
  a very distinct protocol for surveillance with
• 20:56
  imaging where you can really determine target
• 20:59
  lesion revascularization, for instance, is the
• 21:02
  strength of a randomized control trial. Sure.
• 21:05
  Yeah, that's... What we have here, you cannot
• 21:08
  directly compare both. So in your opinion, the
• 21:11
  main limitations of SweetVask is only the fact
• 21:15
  that it's registry. You have more noise, more
• 21:17
  and more background noise in that, in my opinion,
• 21:20
  because you try to collect all the outcomes,
• 21:24
  but you have to accept that some outcomes may
• 21:27
  not be due to the choice, the randomized choice
• 21:31
  of this or that device. That's my opinion. What
• 21:34
  about you? Just before we move on, Dr. Joy, is
• 21:36
  there any weaknesses in SweetVasque you'd like
• 21:38
  to take the opportunity to point out for us?
• 21:40
  Sweet, but I totally agree with you there. I
• 21:43
  think you've summarized it well. Yeah, you see
• 21:49
  it as the trial. You can answer some of the endpoints.
• 21:53
  Thank you both. Those are really helpful counterweights.
• 21:56
  Despite these weaknesses, some have gone as far
• 21:59
  as suggesting that sweet PAD could signal the
• 22:02
  beginning of the end for drug eluting devices
• 22:04
  in PAD. Others argue it may actually be over
• 22:08
  -interpreting sweet PAD4 by treating all packet
• 22:11
  XL devices as a single class despite major differences
• 22:14
  between balloons, stents, drug doses, and release
• 22:17
  kinetics. So perhaps we are judging a whole family
• 22:20
  of devices by the average of its members. So,
• 22:23
  Professor Roy, where do you stand on that spectrum?
• 22:26
  Do you think that's an overreaction or does Sweetpad
• 22:29
  genuinely challenge the foundation of drug -eluting
• 22:31
  technology enough to warrant a major rethink?
• 22:34
  Thank you. So my take on Sweetpad is that you
• 22:38
  should not use drug -eluting technology on everyone.
• 22:41
  So that was what was in Sweetpad. We either used
• 22:43
  it or did not use it on everyone that was included.
• 22:47
  So I think we need to understand which patients
• 22:50
  need it. Can we be more patient -specific? Does
• 22:53
  it have a difference if it's a restenetic lesion
• 22:56
  that might have more smooth muscle cell proliferation?
• 22:59
  How does it work on a subintimal versus the intraluminal
• 23:03
  recanalization? So I think hopefully we might
• 23:06
  get some more data from the SWEDPAD, but I think
• 23:10
  we will need more evidence. And then also the
• 23:13
  antithrombotic treatment in SWEDPAD was... It
• 23:16
  was pragmatic. It was not controlled. So that
• 23:20
  also makes it hard to take. If I may add, there
• 23:26
  is a rule, a basic rule. If you want to implement
• 23:31
  or recommend a new technique or a new device
• 23:34
  or a new decision in everyday clinical practice,
• 23:38
  it has to be better cost -effective against the
• 23:42
  standard of care. So far... This standard of
• 23:46
  care is plain balloon angioplasty in terms of
• 23:50
  endovascular revascularization. And that's all
• 23:53
  we did and discussed. It's not about a safety
• 23:56
  signal. It's about, is there an added value,
• 24:01
  an added benefit, an added net benefit to the
• 24:04
  patients due to this device technology? And I
• 24:08
  take it from your tone that you feel that there
• 24:10
  might not be. I am very, very free in the decision
• 24:13
  making in my everyday clinical practice. As far
• 24:17
  as I'm concerned, this may... change in the future
• 24:22
  because we are living in an inflation, increasing
• 24:24
  healthcare costs. So maybe we have to decide
• 24:28
  twice before we choose a costly device over a
• 24:32
  less costly device in the future. Right now,
• 24:34
  it's quite free, at least in Germany. But I use
• 24:38
  these devices for certain cases, as was said
• 24:41
  a minute earlier. I don't think there is enough
• 24:45
  evidence for a first -line recommendation. That's
• 24:48
  all. So if I understand correctly, for both of
• 24:50
  you, this story up to now has brought us to a
• 24:53
  place where we're being more selective in our
• 24:55
  use of this technology. And actually the selection
• 24:59
  of patients is what's going to have to drive
• 25:01
  future research. That's where our focus should
• 25:03
  be. always been the case and also the best cli
• 25:07
  bezel discussion and the prospective german vast
• 25:11
  cohort study emphasized that it should always
• 25:14
  be an individual decision a patient individual
• 25:16
  decision what works works if you are reasonably
• 25:19
  good with your techniques and you are a good
• 25:23
  interventionalist and i mean you have good results
• 25:27
  and the very best you count your results then
• 25:30
  you should continue doing that if you are a very
• 25:33
  very decent bypass surgeon and you are good with
• 25:36
  your bypass surgery then you should do that as
• 25:39
  well but if you are a weak bypass surgeon or
• 25:41
  weak interventionalist you should consider to
• 25:44
  yeah Get help. Thank you. That puts it into perspective
• 25:48
  very nicely. Whenever we sit on the spectrum,
• 25:51
  Sweetpad has pushed a broader question onto all
• 25:54
  of us. Are our endpoints really capturing what
• 25:57
  matters to patients? We would like to use Sweetpad
• 26:00
  to talk a bit about choosing the correct outcomes.
• 26:02
  One of the major themes emerging from Sweetpad
• 26:05
  and now echoed in the updated DSVS recommendations
• 26:08
  is the growing disconnect between technical success
• 26:10
  and clinical benefit. For years, The feed has
• 26:14
  celebrated better patency and lower target lesion
• 26:16
  revascularization as markers of progress, but
• 26:19
  SweetPet challenges those improvements and how
• 26:22
  they actually translate into outcomes patients
• 26:24
  notice or value. The new guidelines update goes
• 26:27
  even further by suggesting that modest reduction
• 26:30
  in intervention may not justify routine device
• 26:33
  use if they fail to improve quality of life or
• 26:35
  working capacity in a clinically meaningful way.
• 26:39
  Now, Dr. Behrend, has this changed the way you
• 26:42
  personally define success after endovascular
• 26:44
  intervention? And do you think our current trial
• 26:47
  endpoints still reflect what matters most to
• 26:49
  patients with PAD? Well, alongside patient -reported
• 26:53
  outcomes like the limb salvage, quality of life,
• 26:58
  pain release, walking capacity, all these patient
• 27:03
  -reported outcomes measures, of course, it's
• 27:07
  important to have rather technical endpoints
• 27:10
  if you consider the long -term strategy like
• 27:15
  if you know this intervention will fail after
• 27:18
  a month or two or after a year then you should
• 27:22
  consider this fact but the person who is getting
• 27:26
  treated by you. The patient is less interested
• 27:29
  in targets, liver, re -vascularization, primary,
• 27:32
  secondary, assistant, patency and everything
• 27:34
  like that. They just want to get out of the hospital.
• 27:38
  They want to keep the leg. They want to move.
• 27:40
  They want to have less pain. The majority of
• 27:44
  the trial evidence was on patient with intermittent
• 27:47
  claudication, not on CLTI. That's a completely
• 27:50
  different game, but let's... Keep it with intermittent
• 27:53
  claudication. In intermittent claudication, for
• 27:55
  instance, and we just published a paper in the
• 27:58
  JVS on the German VASC outcomes, patient -reported
• 28:02
  outcomes, walking capacity, it matters that you
• 28:06
  choose the right patient. It matters if the patient
• 28:09
  is severely obese or already retired, is not
• 28:13
  mobile. You should consider this instead of a
• 28:16
  target lesion revascularization because if there
• 28:19
  is no symptom, relief and they don't have a an
• 28:24
  improved walking capacity after a year then this
• 28:28
  means nothing if the lesion is re -occluded or
• 28:32
  is occluded after a certain time and the pain
• 28:39
  is the same, the quality of life is the same,
• 28:41
  this is not helping the patient. So I think it
• 28:44
  should always be patient -reported outcomes and
• 28:47
  patient -related outcomes like limb salvage for
• 28:50
  CLTI, etc. In parallel to SWEETPAD, another important
• 28:55
  study that counterbalances the discussion is
• 28:58
  the REALDIS study, a prospective multicenter
• 29:00
  Japanese study led by Dr. Shibata, of which the
• 29:03
  three outcomes were published in the European
• 29:06
  Journal mid -2025. The REALDIS provided vital
• 29:10
  real -world counterweight to the aforementioned
• 29:13
  Imperials RCT, again comparing Cook's silver
• 29:18
  PTX to the Boston Scientific Iluvia. Dr. Joy,
• 29:22
  can you tell us a little bit about the results
• 29:23
  of Rialdez and do you have any important take
• 29:26
  -home messages for your clinical practice? So
• 29:29
  the Rialdez study, as I understand it, it's an
• 29:31
  observational study then that compared once again,
• 29:35
  as you say, to the polymer -coated Iluvia stent
• 29:37
  to the polymer -free silver PTX. And they didn't
• 29:41
  really show any difference in results in the
• 29:44
  FEMPOP segment. Interestingly, and I think it
• 29:47
  can be, they had some higher instant occlusions
• 29:51
  in the patients treated with alluvia. But once
• 29:53
  again, coming to the real, what matters to the
• 29:56
  patient, it didn't really affect which they chose.
• 30:00
  So I think it doesn't add so much, as I said
• 30:04
  before, between drug against no drug, but between
• 30:08
  different drug technologies. But it's more data
• 30:10
  that is available. In the drug story, right?
• 30:16
  Right. Which is helpful in a certain way, isn't
• 30:19
  it? Right, yeah. And yeah, very interesting.
• 30:21
  And it comes also from another population in
• 30:24
  Japan. I think that's also very interesting.
• 30:26
  Fair enough. Dr. Behrend, what other evidence,
• 30:29
  in your opinion, should we be reading closely
• 30:31
  in the debate concerning the efficacy of drug
• 30:34
  -eluting technology? What would you like to draw
• 30:36
  our attention to? What should the trainees go
• 30:38
  home and read? I don't think there is any study
• 30:43
  that will convince me during the next few months.
• 30:46
  I think one of the most important guidelines
• 30:50
  that we all should read more often is the APAT
• 30:54
  and intermittent claudication guideline, because
• 30:56
  we can help much more with best medical treatment,
• 30:59
  optimal pharmacological treatment than with any
• 31:02
  balloon. Coating with a new fancy diamond ceiling,
• 31:10
  you know. Nothing helps more than putting patients
• 31:15
  on statins and helping them to stop smoking,
• 31:18
  for instance. It's a much better improvement
• 31:20
  than with any device. On the other hand, the
• 31:24
  global vascular guideline update will be hopefully
• 31:27
  ready end of next year, maybe. The International
• 31:31
  Working Group of the Diabetic Food Guideline
• 31:33
  will be already beginning off next year. So I
• 31:36
  think the people should read the ESVS and inter
• 31:39
  -society guidelines. Thank you. That gives our
• 31:42
  listeners a very useful reading list. And now
• 31:45
  a lot of our discussion and the large portion
• 31:48
  of the body of evidence has been focused on Patektaxel.
• 31:50
  But what about the Lyme family of drugs? serolimus
• 31:54
  and everolimus have been there all along but
• 31:57
  are starting to pop up more in the PID literature
• 32:00
  too. Professor Zhou, can you explain the differences
• 32:03
  for us? Well, I will try here. So, paclitaxel
• 32:06
  is a cytotoxic drug and why is it called that?
• 32:10
  So, what paclitaxel does is that it binds to
• 32:13
  tubulin when the cell is about to divide. The
• 32:16
  cell has gone through the whole cell cycle and
• 32:18
  is going to divide and that's when paclitaxel
• 32:20
  binds to it and stops it from dividing. The cell
• 32:23
  really gets distorted. All the DNA, everything
• 32:26
  has doubled. So then the cell just dies because
• 32:30
  it's become distorted. Cyrolimus and everolimus
• 32:33
  drugs, on the other hand, they are affecting
• 32:36
  the cell in the cell cycle at an earlier stage
• 32:38
  between the G0, G1 going to the S phase. So they
• 32:42
  stop the cell from going into the S phase. So
• 32:44
  it's more of a cytostatic drug. And what has
• 32:48
  also been shown is that they also affect inflammation.
• 32:51
  because it affects also T cells and other inflammatory
• 32:54
  cells. And I think that was probably the explanation
• 32:58
  they took when it came to the cardiac coronaries,
• 33:01
  because there is a lot of inflammation, which
• 33:04
  we know is also happening in these unstable plaques
• 33:06
  in the carotids, for example, more than the plaques
• 33:09
  in the legs. So, yeah, at least in our setting,
• 33:12
  we have access to two limus balloons, the Magic
• 33:16
  Touch and the Solution SLR. And recently, there
• 33:20
  was a publication in the New England Journal
• 33:21
  with a magic touch, which showed some benefit
• 33:24
  with reduced interventions. But the problem was
• 33:27
  that a large part of those patients were claudicants.
• 33:30
  And in our settings, we do more CLTI patients.
• 33:33
  Thank you, Professor Roy. So different mechanisms,
• 33:36
  different safety margins, maybe. Now, Professor
• 33:40
  Beran, do you see a big future for these drugs
• 33:42
  in the PID technology? What evidence would you
• 33:45
  like to draw our attention to? I think there
• 33:48
  will always be an added value and role of these
• 33:51
  drugs in selected cases. And that's what the
• 33:54
  guideline update also states. I notice a shift
• 34:01
  towards Zerolimus, and I think that is probably
• 34:04
  the favorized strategy in the near future, but
• 34:09
  that's just a gut feeling. Thank you for sharing
• 34:12
  your gut feeling. Before ending our podcast,
• 34:15
  I'd like to open one more important topic, the
• 34:18
  effect of the industry lobby. This question is
• 34:20
  for both of you, Dr. Choi and Dr. Berend. In
• 34:22
  your opinion, how much does the industry lobbying
• 34:24
  play a role in keeping drug -eluting technology
• 34:27
  in the game, so to speak? And how should this
• 34:30
  be handled? Thank you. So I think it's a double
• 34:33
  -edged having the industry. Without the industry,
• 34:36
  we would not be developing a lot of the treatments
• 34:39
  we have today. So we have to take them. On the
• 34:42
  other hand, then, The industry also affects us
• 34:45
  in trying to make us use these technologies.
• 34:47
  So we have to be very careful. And I think when
• 34:50
  you look at evidence that is being published,
• 34:53
  you have to think, is this coming from an industry,
• 34:55
  heavy authors or industry coming from the industry,
• 34:58
  or is it coming from some independent source?
• 35:01
  So it takes a lot in us and in those who write
• 35:04
  our guidelines, which I think is very important
• 35:06
  in trying to weigh the evidence. Yeah, I completely
• 35:10
  agree. I think it's vital to research to have
• 35:14
  strong partners in medical device industry and
• 35:17
  pharma industry. Without them, larger, high -quality
• 35:22
  studies would never have happened. And I think
• 35:25
  they are investing not enough these days in PAD
• 35:28
  cohorts. It's completely okay to have industry
• 35:32
  connections for the authors, but... It's also
• 35:37
  a risk of bias influences how you interpret data,
• 35:41
  how you present central conclusions. And this
• 35:45
  is why the only rule is to transparently disclose
• 35:48
  your connections. And then it's completely okay.
• 35:51
  And the readers, on the other hand, should always
• 35:54
  consider that enthusiasm is not always equal
• 35:59
  to evidence. Because if you were a PI for a certain
• 36:05
  study and this appears to me as well in registry
• 36:08
  studies now of course i'm convinced that this
• 36:12
  is good research but i can do mistakes so if
• 36:16
  you want to ask someone if registries are over
• 36:20
  interpreted you should not ask me i mean and
• 36:24
  if you ask a trialist it would be completely
• 36:28
  different so i think it's always a matter of
• 36:31
  um yeah understanding the challenges of competing
• 36:36
  interests. Thank you for those honest insights.
• 36:39
  And thank you for all your answers and insights
• 36:41
  throughout this podcast. That brings us to an
• 36:44
  end for today, although this is clearly a conversation
• 36:48
  that will continue. So once again, thank you
• 36:50
  to Professors Roy and Berend for making this
• 36:53
  time for us and engaging so openly in this look
• 36:58
  at the historical and contemporary evidence surrounding
• 37:01
  the safety and efficacy of drug -eluting technology
• 37:03
  for peripheral artery disease. Thank you so much.
• 37:06
  It has been a pleasure to be here and also a
• 37:08
  pleasure for me to read up once again on all
• 37:11
  these studies. Thank you. Thank you very much.
• 37:14
  That was fun. Also, thank you to our listeners
• 37:16
  for tuning in again and listening to the SVS
• 37:18
  podcast. We look forward to welcoming you again
• 37:20
  next time. Goodbye.