The superficial femoral artery (SFA) is an area of intense research interest and multiple options for treatment. In this Q&A, Gary Ansel, MD, FACC, explains the takeaways from recently released data on various devices and therapies. Dr Ansel is an interventional cardiologist at Riverside Methodist Hospital in Columbus, Ohio, and he is a faculty member at the upcoming International Symposium on Endovascular Therapy (ISET), which takes place February 3-7, 2018 in Hollywood, Florida. He will be presenting several cases, as well as speaking on the current management of superficial femoral artery.
Could you tell us about what some of the most recent randomized trials on the SFA have evaluated and comment on their findings?
We want to evaluate everything compared to our traditional cornerstone, which is balloon angioplasty. However, patient-level data from past randomized trials that used angioplasty versus stent grafts, bare metal stents, drug-eluting stents, and drug-coated balloon have shown that the 12-month patency rate for with plain balloon angioplasty of a medium-length lesion of 4-15 cm is about 33%. We need to improve on that percentage because that’s not adequate for our patient population.
When we look at what data are available in terms of comparisons, there are the drug-eluting stents versus plain balloon angioplasty and bare-metal stents. The ZILVER PTX trial, which was an investigational device exemption (IDE) trial, showed that drug-eluting stents are better than plain balloon angioplasties and bare-metal stents through 5 years of follow-up with fairly stable patency rates that are very good clinically.
That initial drug-based trial in the periphery left us parallel to the coronary pathway, which is where drug elution has really taken over. Unlike the coronaries we also have gone to drug-coated balloons, and there have been randomized trials looking at the Lutonix drug-coated balloon, as well as the IN.PACTs drug-coated balloon. Both trials showed clinical benefit that was better than balloon angioplasty, though this benefit was certainly most obvious in the IN.PACT dataset. Nonetheless, both datasets showed showed statistical benefit at 1 year for drug-coated balloon and now we are getting positive multi-year results as well.
Regarding subsets, various patient populations and registries have shown that the drug-coated balloon platforms have done very well in multiple subsets beyond those typically enrolled in these approval trials such as longer lesions, chronic total occlusions, etc. However, severe calcification is one of the subsets in which there appears to be room for improvement.
I should also mention that there are two nondrug based stent datasets that have been different than the rest. Most tubular nitinol stents are bare metal and have a reasonable patency at 1 year but a continued decline over the next 2 to 3 years. However, the Supera, which is the nitinol interwoven stent, has shown that it has good patency that stays fairly stable at 3 years, even in calcified lesions. A more stable restenosis pattern was also seen in a European randomized trial of the BioMimics swirl pattern stent.
We have a randomized dataset for Heparin-bonded stent grafts too, which have been shown to be better than balloon angioplasty. Recently, the Viastar trial, which was conducted in Europe, showed that stent grafts performed better than bare-metal tubular nitinol stents and were not affected by lesion length.
All this tells us that we have several different technologies—drug-coated stents, drug-coated balloons, the nitinol interwoven stent, and a stent graft—that have shown improvement compared with plain balloon angioplasty and bare-metal stents over the long term. The only technology that lacks randomized data against balloon angioplasty is atherectomy. We have large registry datasets that appear to show efficacy, but obtaining a randomized dataset is still important.
Have there been any head-to-head comparisons of the devices, or are most comparisons versus angioplasty?
The devices have been compared head-to-head to bare-metal stents for stent grafts and for drug-coated stents, but nobody has compared drug-coated balloons to bare-metal stents, and again, atherectomy doesn’t have any randomization beyond a small Excimer laser dataset.
So far, drug-coated balloons have not been compared to each other, though a new trial, the TRANSCEND trial, will be evaluating a new drug-coated balloon from the SurModics company versus the IN.PACT drug-coated balloon. This will be one of the first head-to-head trials, and we are excited about the trial design.
From a bare metal standpoint, the Veryan BioMimics stent, which recently completed a trial in the United States but is not yet available, has previously demonstrated a more stable patency in a randomized trial against another bare-metal stent, the LifeStent. When the BioMimics stent, a swirl type of stent, was randomized against the LifeStent, a straight stent, the European results showed that the BioMimics demonstrated a superior patency at 2 years. The US trial results are still pending.
What factors do you consider in choosing among different treatment options?
The major factors we consider are the blockage characteristics. With severe calcification, we’re leaning away from standard drug-coated balloons because there is a lot of recoil from those types of blockages, and there seems to be less drug uptake and less restenosis benefit. In those cases, the operators at our institution have to decide whether to use a drug-coated stent that uses a nitinol tube stent, or a Supera. The decision between which of those two stent lines is based on the operator’s experience of resistance to full deployment. The two stents have a different crush resistance level. If a drug-eluting stent is fully deployed, it’s very good, but if it’s under deployed, its efficacy decreases. We have to be aggressive in our vessel preparation so that we are able to optimally deploy the Supera to full deployment in a calcified lesion.
We test the vessel resistance and recoil with balloon angioplasty prior to the decision of which stent we will use, in calcified lesions. Here is where our institution may also choose to use atherectomy preparation with these stents or even with drug-coated balloon, despite the paucity of data available.
The other factor we consider is patients who have really long lesions, ie, lesions greater than 15-20 cm. Patients with this situation tend to need more frequent episodes of retreatment. For those types of blockages, stent grafts have certainly shown that the length of lesion does not affect their patency rate. There is some concern about thrombosis because you are using a stent graft, which can cover collateral arteries; however, as long as you’re staying above P2, none of the randomized trials to date have shown an increased risk of acute thrombosis that puts the patient at risk compared to bare-metal stents. It’s only once you get below P1 that thrombosis can become more of a concern.
If the lesion is not severely calcified, it’s an excellent place to use drug-coated balloons. The data from the IN.PACT long-lesion subset has shown acceptable patency rates without using a prosthetic device. The prosthetic stent devices are potentially an irritant to the vessel in those long lesions, leading to decreased vessel compliance and perhaps a continued nidus for restenosis. Thus, many people are doing long-lesion drug-coated balloons and then spot stenting if there is a place where there is recoil or slow limiting dissection.
We’ll often perform a balloon angioplasty ahead of time and then use a drug-coated balloon if the results appear favorable. If it does not seem favorable, then we’ll use a drug-coated stent or on occasion a drug-coated balloon and a bare-metal stent. These decisions vary from lesion to lesion and individual to individual, as there have been no comparison data to say which of those decision processes is the correct one.
Are there any important topics of discussion in the field over the past few years that you’d want to highlight?
There has been a tremendous trend in using atherectomy in office-based labs (OBLs), but there have been no data to support atherectomy other than registry data. Atherectomy does correlate with the highest reimbursement, so the trend in atherectomy use in OBLs is concerning. In hospitals, atherectomy is down to less than 20% of the cases, even though it is the highest reimbursement. I think the trend in atherectomy use is a curiosity that we’re trying to understand because we don’t have datasets that are driving us to the decision.
Another big discussion right now is deciding whether to use a drug-coated balloon or a drug-coated stent. We don’t have that dataset yet, but I think it will be very telling. Many practitioners would say that both drug-coated stents and drug-coated balloons have shown good patency at 3-5 years, though drug-coated stents show a slightly longer time period.
I would make the decision based on the results of the balloon angioplasty and the amount of calcification. If a vessel is significantly calcified, then we’ll need to use something that gives better luminal growth in that area, such as a stent. On the other hand, I might use a drug-coated balloon if I have a nonseverely calcified vessel, and if have good balloon angioplasty results. Currently, the drug-coated balloon results are good without leaving a prosthetic in the patient’s body, so those factors influence my decision.
Are there any differences in how people practice in different regions in the US, or any procedures that are potentially overused?
Medicare actually thought that procedure use was a significant problem and called a panel together on the topic. My take by the end of that panel, was that the consensus demonstrated that arterial treatments were actually underutilized in the critical limb patients. Of course, we still need a dataset to better understand the problem.
There are certainly both places of overutilization and underutilization around the country because we do see fairly heterogeneous treatment patterns. I personally believe that we are probably underutilizing the use of techniques for patients with critical ischemia.
Do you have any recommendations for combining the various devices, whether that’s in vessel preparation or in other parts of the procedure?
The vessel preparation discussion mostly centers around long lesions and calcification. For all treatments, we want to optimize luminal gain and choose the option that will lead to the fewest repeat procedures. A newly approved device, the Shockwave device, is a lithoplasty type of balloon that helps to fracture calcium. An ongoing randomized trial in the US is examining the efficacy of the lithoplasty device with drug-coated balloon or plain balloon in a randomized fashion for moderate and severely calcified lesions. . When the study is complete, it will be interesting to see if that type of vessel preparation helps with patency.
Regarding combination therapy, we haven’t seen a decrease in patency when drug-coated balloons are combined with spot stenting in limited data sets, though the time intervals are shorter than the drug-eluting stent platform studies. We don’t have a randomized trial to show which of those is absolutely right, so I think that drug-eluting stent currently is preferable because it has a 5-year data set and the other technologies have less followup.
We also don’t have any vessel preparation randomized data at all for longer lesions. This makes it harder to compare and know which course of action to take. Operators should strive to obtain the best patency of the vessel up front and then ensure that we have the right technology, which could be drug-coated stents or drug-coated balloons, or perhaps a Supera nitinol woven stent in severely calcified cases. We have a good deal of data, but we still have data deficits to overcome.
What are your thoughts on what the next generation will be with these devices and/or drug delivery?
I think the next step is better drug elution. If you look at the balloons, the drug material and excipient have been somewhat non-uniform, but I believe the next generation of devices will have smaller debris, better uptake, and more homogeneous transfer. After that, I think the next thing will be can we do that with the Limus type of medications, which are cytostatic instead of cytotoxic. Theoretically, these drugs may be predicted to have a better long-term outcome as we’ve seen in the coronaries.
From a drug-coated stent standpoint, I think we’ll absolutely parallel the coronaries. I expect that either parallel to or after there is improved drug elution, focus will turn to the stent platforms. Current stents, especially in long lengths, adversely affect the vessel compliance and potentially may be a continued irritant for intimal hyperplasia. We need to develop stents that don’t fracture often and that are compliant for the vessel in long lengths, not just the short lengths that we see in IDE trials.
I also hope that we’ll have randomized data on atherectomies. Registries are nice, but they don’t give us the ultimate data that we want. As we try to develop treatment algorithms, head-to-head testing is crucial.
Is there anything else on the topic that you’d like to comment on?
Besides the drug-coated technologies, there is a technology that actually inserts medication into the adventitia through a needle. That has shown some benefit. We still need more data sets, but researchers been using steroids in the adventitia to try to decrease restenosis, and it appears to have a reasonable outcome. However, there’s no randomization to against other more mainstream technologies to know which one is most optimal. These technologies need head-to-head comparisons so that we can really figure out the best, most cost-effective treatment pattern for our patients. We also look forward to the results of the ZILVERPASS trial from Europe comparing Zilver PTX to venous bypass.
Disclosures: Dr Ansel is a consultant for Medtronic, Abbott Vascular, Boston Scientific, WL Gore, CR Bard, Phillips/Spectranetics, and Veryan; has royalties with Cook Medical; and is a board member for VIVA Physicians, a not-for-profit 501(c)(3) organization.