Editorial | In Conversation with Cook Medical - 4 Year Results for the Zilver PTX | Which Medical Device

Andy: I would say we’ve done two things; we’ve done a single arm trial registry and we’ve done a randomised trial. In one, there were some limitations in the randomised trial with no longer lesions than 15cms. The real big value of the two combined together is that there are more than one thousand patients. So the number that we’re talking about is already very big.

 

Phil: And, how long a time period were those 1000 patients recruited over?

 

Andy: Well, we’re going to present 4 year follow-up data 

 

Phil: Is 4 years your maximum data?

 

Andy: Yes

 

Phil: What percentage got to 4 years?

 

Andy: Not all but, for sure, we’ve a huge amount of patients for 3 year data so that can probably be 70-80% of the people. So again, you don’t see many studies after the 3 years. We’re talking about easily  83.2% TLR.

 

Phil: So, what were the inclusion criteria? 

 

Andy: It was different in the single arm and different in the randomised. In the randomised, there was that limitation that I told you about in the lesion length, no longer than 15 cms (Phil: and these were for occlusions?). This was for everything and when you analyse the lesions, the Task C and Task D lesions were worse in the randomised than they are in the single arm, so one of the things that you have to also look at is the lesion complexity, and, we are showing huge lesion complexity so quite a significant amount of Task C and Task D. 

 

Saying that, what we are really seeing is that it depends by country here in Europe.  One of the things that we’re seeing is that with those results claudicant patients that are treated for example in Germany and France are treated differently in the UK, Scandanavia and Spain. But for claudicant patients you now have a real option in order to put in the technology that keeps the vessel open for a long, long time.

 

So, that’s something that we need to start thinking about because with a critical limb ischaemia patient of high complexity, even though in that situation it’s working, really, the benefits are when you have a claudicant patient that as a physician, you cannot miss it – you cannot make a mistake.

 

Phil: The real study there is going to be comparing that with a standard by-pass graft, isn’t it?

 

Andy: Well, we are actually working on a trial like this, also. 

 

Phil: Ok, large numbers I think may be needed to prove any benefit?

 

Andy: Exactly.

 

Phil: For Interventional Radiologists, if you can prove that drug-eluting stents are superior to a surgical bypass, then for a lot of people, that’s going to be fantastic, and, for the patient of course.

 

Andy: I agree with what you are saying but even if it becomes break-even, who wants to have open surgery rather than a minimally invasive procedure?

 

Phil: The difficulty is, of course, is in randomising a group of patients if you give them the option of a minimally invasive treatment which might be as good as or nearly as good as, most patients are going to say, well actually I’d rather not have surgery, I might as well go for the stent.

 

Andy: I’m glad you’ve mentioned that because we were talking yesterday exactly about that topic but now, having that result after 4 years and that technology is working and giving result – and again, I want to insist in that 83.2% in target lesion revascularisation we can start really thinking that we’ve got an alternative to open surgery and we need to show that to the World. We need to so a serious trial, a randomised trial in order to show to the World that there is an option. 

 

There are still discussions outside saying that well open surgery is better than minimally invasive technology. With all respect, open surgery will always have cases but if the technology keeps improving, like it is now, with the ZIlver ptx why would you do open surgery if you have something that is giving you the same or even better results than that. 

 

Phil: One of the things of the SFA, it’s a vessel that’s flexing quite a lot. Did you have many problems with stent fractures in the 4 year follow-up?

 

Andy: Yesterday, stent fractures are one of the things that we covered. Stent fractures are something that are not an issue any more. All the theory of not leaving anything behind. If you’ve got results like this there is no a problem at all I mean were talking fracture rates of what 1-2% something like this. Here, in Europe, we launch the Zilver Flex. Zilver Flex is the platform that we are using for the SFAs. This is a specific design inside the Zilver family which is specifically designed for the SFA. And with that, Zilver Flex, then we put paclitaxel on, adapt it and that’s why the fracture rate is significantly decreased and that’s an important point because lots of people just think about Zilver adapted for the SFA and then paclitaxel on it and that’s why there is a significant reduction also on the fracture rate. 

 

Phil: The follow-up of these patients during the study, was it imaging follow-up or clinical?

 

Andy: In some years, it was Doppler ultra-sound and in some it was x-rays so it has been very detailed. If I’m not wrong then the first two years were by x-ray but I’m not 100% certain. We didn’t want to do a Doppler ultrasound only so that’s why I’m not saying it was a Doppler ultrasound because in a Doppler ultrasound you don’t see fractures. And, I remember talking with a lot of physicians at the beginning who were telling me ‘well, I don’t see any fractures’ its because with a Doppler you don’t see fractures so that’s why we are doing x-ray and we do follow with x-ray in order to capture some fracture rates because if not, you don’t see it.

 

Phil: What were the results like looking purely at the patients’ symptoms at 4 years, comparing the 2 groups?

 

Andy: We will see today on the walking distance that they are doing and ABI data that we are monitoring but in general, if you’ve got 83.2% of the target lesion revascularisation I understand that the patients are dong far better than they were doing before. So, looking at what we’ve been monitoring, and I’ve not seen the 4 year data completely, we’re just presenting a bit here and in Vegas we’re going to present a bit more data. We will be able to say more about how the task lesion has been evolving, so for sure what we have seen is the Task Cs and Ds have all moved to As and Bs so have significantly increased in the walking distance and ABIs moving up to 0.9 and 1s. From that data, I take the freedom to say that they are feeling better. 

 

Phil: What refinements or improvements do you think could be made to the Zilver PTX or you would expect to be made in the future?

 

Andy: One of the things that we need to start evaluating is really following-up our patients in a better way. So, what I see is that in general in lots of places, a patient comes in and is treated and then sometimes we don’t know what happens with that patient. It’s the most difficult thing in the twilight this is to follow-up patients and I think that that’s something that we need to start looking at as a society – as a medical society – and everybody should start evaluating what happens after 2,3,4,5 years.

 

Phil: As Interventional Radiologists, we don’t often see what happens to these patients unless they come back for reintervention. 

 

Andy: I think that’s something that I really appreciate that we can evaluate, because today we are doing treatments to people and [it may be my German part of the brain] but it is we think it’s working but do we really know it’s working and one of the things that comes out from the studies is that 50% of angioplasties fail. So, that’s one of the things that I’m saying that if you’ve got a claudicant patient you need to start evaluating and following-up. So that’s one first thing that we’ve learned to improve on. On the Zilver PTX side, with the results that we now have, the thing we are working on is to have longer lengths because in the SFA we need this. We are very happy with how it’s going. 

 

Phil: Okay, what about the size of the delivery system, can you improve on that?

 

Andy: At the moment, it’s at 6 Fr system. There are some talks to maybe doing a 5 Fr system but we don’t see there really is a limitation of using that technology, not really for now. But yes there are some talks.

 

Phil: The Zilver PTX was recalled at one point and there were some problems. Can you tell me a little about that?

 

Andy: Yes, basically, we found out that for one of our suppliers, we did not have the right quality controls with that supplier so there was a slight deviation that was accumulated. What we have put in place is now a process to evaluate that provider better. 

 

Phil: What was the deviation? What particular aspects of the stent?

 

Andy: It was not the stent, it was the deployment system. It was on the material specification side which has now been all solved and so we are back again with that product. And, I think that one of the things that we’ve done very well as a company is to inform and keep informing everybody. It was not a major thing. It was 2 patients in Japan and not many companies take a position on such a major project - to stop the whole thing. This is one of the things that makes me proud to be with Cook. Two patients is by far enough to take top position and make sure that we are 100% safe [Phil: Good] And, this is something with the number one product in the company and to stop all those things makes me feel very safe. If my father needs something on the SFA I would put in a PTX.

 

Phil: That takes me on to my last question. As a clinician, I have a patient with a long, chronic total occlusion of the SFA. Surgery’s not really an option for this patient. What would make me use a Zilver PTX rather than say a drug-coated balloon?

 

Andy: A long [Phil: perhaps a medium, Why would I use a Zilver PTX rather than a drug coated balloon]. What data do you have about drug-coated balloons?

 

Phil: I couldn’t quote you any data off the top of my head.

 

Andy: How many trials are there outside more than 200 patients and on drug-coated balloons?

 

Phil: I’m sure you can tell me the answer to that.

 

Andy: There aren’t. So, going back to the point with that technology that we’ve got available. Lots of people have been placing PTX for highly complex cases and its working fine for them but really, the value that I see on that one is that when you’ve got a claudicant patient or a diabetic patient, that’s due a first intervention, and you are evaluating on doing a balloon or a stenting, that’s the moment to use a PTX. In 81% of the people already, at Charing Cross, and yesterday again its very clear to say that drug eluting technology is the way to go. That’s the first thing, so once you’ve decided this, I would really recommend that when you are in that claudicant patient, that diabetic patient you know that he’s going to have a long life and you want to have a good long-term result – it’s the moment to use a PTX [Phil: It seems to make sense to me].

 

Drug-eluted balloons have a place in shorter lesions and initial stages where it makes sense to try that technology but in a certain moment, while you are thinking ‘should I stent?’ …. that’s the moment to put a PTX in and do a good follow-up on that patient because the vessel is going to be open for a long, long time.

 

Phil: Andy thank you very much

 

ENDS