Inside access

Misra S, Atkinson C, Dermody M, et al. IN.PACT AV Access Post-Approval Study of a Paclitaxel Drug-Coated Balloon for the Treatment of Dysfunctional Arteriovenous Dialysis Circuits. JVIR, 2026;37.

Can you tell us about you, your team, and your institution?Sanjay Misra, MD, FSIR: I'm an interventional radiologist and professor of radiology at the Mayo Clinic in Rochester, Minnesota, where I work in a group of 15 IRs. I’ve been funded by the NIH for two decades, looking at why arteriovenous fistulas (AVFs) and grafts fail. My research was funded by SIR via a pilot grant. I am the principal investigator of a vascular biology lab that has 10 people in it, with the goal of identifying treatments that will prevent vascular stenosis. We recently showed that mesenchymal fat derived stem cells were protective for stenosis development and improved arteriovenous fistula maturation, and we are now investigating other therapies. I am also the associate director for the Center for Biotherapeutics in Rochester, which really aligns well with my translational practice. At our facility, many of the AVF interventions are referred to IR for treatment.

What inspired you to investigate this topic?Dr. Misra: I was asked by Medtronic to serve as principal investigator for a post-market analysis for their technology, which had shown in a randomized controlled trial that it was superior to plain old angioplasty. Robert A. Lookstein, MD, FSIR, had published the initial paper in the New England Journal of Medicine, and we were part of that study.
One of the challenges of any technology is that once it's approved, how will it work in patients in the real world? This study investigated the impact of Paclitaxel drug-coated balloons in a new cohort. We explored:

1. Does it work as well as the randomized study?
2. Is the safety profile the same as the randomized study?
3. What are the outcomes for these patients once you're outside the pivotal study?

What were the key takeaways from your research?

Dr. Misra: The key takeaways are the safety profile. It is safe and effective. We showed that our 12-month data was very similar to the randomized study. So, it performed similar to the findings from the NEJM paper. The other large safety question the FDA had was regarding infections. I’ll remind readers that when the initial study was completed, we were still in the pandemic, and there were associations with COVID-19. However, these patients needed their fistulas working, even in COVID, because otherwise they were unable to get dialysis.
They needed a functional fistula, and so the FDA was querying to make sure that the technology is truly as safe as we believed. Our study highlighted the safety profile as well.
So, the key takeaways for me are safety, both at a patient level and at a device level, and then efficacy at a fistula level. One can surmise that patients will receive better dialysis if their fistula is working better.

According to the paper, you found a 70% target lesion primary patency rate (TLPP). From a practical standpoint, what does that mean for dialysis patients and the physicians who manage these access sites?

Dr. Misra: There are several forms of dialysis. You can have dialysis at home, or at a center, such as with a hospital or one of the dialysis units. Patients who receive dialysis at a hospital spend time going to the dialysis unit three times a week for 3 to 4 hours, in addition to commuting time.

Patients visit the facility 12 times a month for dialysis, and they spend half a day receiving treatment. One could say that our treatment allows for a better quality of life. This was not measured in these studies, but for the patient, it has a huge impact, because they’ve already committed themselves to quite a bit of work in order to stay on dialysis.
Now for the providers, the frequency of interventions during that time gets reduced which means less time in the procedural cath lab for patients.

Are there any unanswered questions that remain? And if so, are there any follow-up studies or further planned analysis in this project?Dr. Misra: There are always more questions that need to be addressed as you're digging into a complicated problem. Dialysis patients are very sick and are often excluded from randomized controlled trials involving the legs or the heart. Really, everywhere that creatinine is abnormally elevated, these patients are excluded from being part of those studies. They're not well studied. Having a data set to study them in and to assess the durability of the treatment is critically important. What that means is follow-up studies looking at 3-year and 5-year outcomes are being planned.

In the real world, or at least in my world, these lesions are not indicative of the general patient population. If you have 100 patients, depending on where you practice, we may have shown a benefit that will impact maybe 20–30% of your practice. Patients don't come with just one stenosis. They come with multiple stenoses that don't fit into what we studied. This was studied in parallel in an extended cohort which focuses on a more severe phenotype with severe stenosis and lesion characteristics. That paper will be coming soon and focuses on the outcome of these patients when treated with this technology. In the initial study, we have one lesion. But can you treat three lesions this way? Can they be longer?

Additionally, we know not every patient has a fistula. There are patients that have grafts placed. For example, if you don't have the right anatomy in regard to the size of the vein or the diameter of the artery, you're at risk of not getting a fistula, and you may get a graft. So, the next question is, how do grafts perform with drug-coated balloons? That also is being investigated in the extended cohort study.

I also have an interest in understanding if we can improve the target lesion primary patency from 70% to a higher percentage. Is 70% as good as it’s going to get, or are there ways of augmenting it so that number can be closer to 90% or 100%? This may include other therapies, other drugs, or combination drugs, for example. Maybe not just Paclitaxel, but perhaps another drug that’s not in the same pathway which will be synergistic and provide an added benefit.