Stefan Müller-Hülsbeck, MD, PhD
Medical Director, Department of Diagnostic and Interventional Radiology/Neuroradiology , Ev. Luth. Diakonissenanstalt Flensburg, Flensburg, Germany; University of Kiel - Faculty of Medicine, Kiel, Germany.
The primary objective of the IMPERIAL trial is to evaluate the safety and effectiveness of Boston Scientific Corporation’s Eluvia Drug-Eluting Vascular Stent System for treating superficial femoral artery (SFA) and/or proximal popliteal artery (PPA) lesions up to 140 mm in length. This trial includes a long-lesion substudy to evaluate the safety and effectiveness of the Eluvia stent for treating SFA and/or PPA lesions >140 mm and ≤190 mm in length. (Clinicaltrials.gov identifier NCT02574481).
Some years ago we started with the so-called MAJESTIC trial and I was the PI for the MAJESTIC trial, which was running worldwide with dedicated centers in Australia, New Zealand, and Europe. In this dedicated trial, we recruited 57 subjects, who were treated with the Eluvia self-expanding nitinol stent. This stent is built on Boston Scientific’s Innova bare-metal stent platform. This stent is unique because it works in combination with a polymer (PVDF-HFP) that has been proven in cardiology in Boston Scientific’s Promus stent. We combined this polymer with the drug paclitaxel; in doing so, it was possible to create some kind of drug release over time. That means once the stent is implanted, some sort of intermediate drug release occurs and then over time there is sustained drug release up to 360 days. This is completely different from the Zilver PTX stent, which is already available in Europe and the United States.
The MAJESTIC study is a prospective, multicenter trial. It’s a non-randomized trial because in this trial we only tested the safety and efficacy of the Eluvia paclitaxel-eluting stent. As mentioned earlier, we included 57 subjects. One of the main inclusion criteria was a lesion length up to 140 mm. That means we could treat occluded segments or severely stenosed segments. One of the unique features of this trial is that we have to deal with a lot of comorbidities. A lot of patients suffer from diabetes, and many have severe calcification, which was quite challenging for this type of trial. In spite of these kinds of challenges we have obtained very encouraging data. For example, the primary patency rate within 1 year was extraordinarily high, at 96.1%. At the 2016 Veith Symposium, I presented the 24-month data, which were very encouraging and showed very high freedom from target-lesion revascularization (TLR) rate of 91.3%. These data match with the quality of life of the patient, which is of upmost importance. Thus, this new self-expanding stent technology featuring paclitaxel in combination with a proven polymer is showing encouraging results in terms of clinical benefits for the patient.
Initial Study Results
I think the initial high primary patency at 12 months was very surprising, and has probably proven the concept that the drug elution over time in the Eluvia stent is working. It was very encouraging that we haven’t seen any problems due to the polymer. A lot of physicians have concerns when they work with polymers combined with bare-metal stents. In previous trials such as STRIDES and SIROCCO, the combination of a bare-metal stent with a polymer was not that effective in terms of primary patency and in terms of TLR. The polymer itself probably caused some problems resulting in restenosis, meaning a decrease in primary patency and an increase in TLR rates. However, this was not shown with the Eluvia stent, which was safe. As mentioned earlier, we had no concerns with this particular polymer because it has already been proven in cardiology in a balloon-expandable drug-eluting stent platform using the same polymer.
Today, we have two different stent platforms dealing with drug elution. We have the Eluvia stent and the Zilver PTX stent, which were directly compared in the IMPERIAL trial in a 2 to 1 randomization. The major difference between these two stent platforms is the fact that Zilver PTX doesn’t work with any carriers, so the drug is on the stent. Once the drug is on the stent, most of the drug will be immediately released during the first days or first weeks after implantation. In contrast, the polymer in the Eluvia stent is a little bit different, because it provides intermediate drug release, meaning that you can really predict how much of the drug will be released within a certain timeline and it is guaranteed with this polymer. Over a certain time, up to 360 days, the drug is released. I think this is the major difference and MAJESTIC has proven that the concept using the Promus polymer in combination with paclitaxel on a self-expanding nitinol stent is working.
I think these first-in-human data will relieve some of the concerns over using polymers in stents, and the objective of the IMPERIAL trial is to remove this concern entirely. The primary objective of IMPERIAL, which completed enrollment earlier this year, is not to show that Eluvia stent is better than Zilver PTX. Rather, we want to show that the polymer is safe, and that the Eluvia is as safe as Zilver PTX, which doesn’t work with any polymer or any carrier. It will be a positive side effect if we can show at 1 year, for example, that primary patency and TLR rates are better with Eluvia than with Zilver PTX, but at this point, I think both drug-eluting stent platforms, Zilver PTX and Eluvia, are working and the data we have seen so far from both the Zilver PTX and MAJESTIC are very encouraging.
Nowadays, we talk about how to treat our SFA patients and how to treat our claudicants suffering from femoropopliteal disease, and I think we should always keep our treatment strategies sharp and simple. I believe we need to determine some kind of treatment algorithm that should always start with PTA – meaning we should prepare the lesion in an adequate manner by ballooning the lesion first. Once we obtain a good result, I think we can say nowadays that one should go ahead with drug-coated balloon technology. However, if the result is suboptimal, then I think from current perspective and from current trial data, we have to rethink how to proceed. From my personal perspective, I think there is a shift in the direction in terms of drug-eluting stent technology. When there is the need for a stent, I would vote for a drug-eluting stent, but that doesn’t mean that drug-eluting stents will be used all the time. So we need to find a treatment algorithm that starts with PTA and then we must distinguish whether we should use drug-coated balloons or drug-eluting stents.