At the 2014 VEITH symposium, Dr. Andrej Schmidt, MD, senior interventionalist at the University Clinic of Leipzig in Germany, presented results from a single-center study using paclitaxel-coated drug-eluting balloons for infrapopliteal lesions. Vascular Disease Management spoke with Dr. Schmidt about the results.
Q: What were the objectives of the study?
A: When the first drug-eluting balloon (DEB) from Medtronic became available, we thought to use it in the lesions where drug-eluting stents (DES) would not be an option, which was long lesions. These are typical lesions in patients with CLI, and so far the only solution for those patients was noncoated balloon treatment. We knew from one of our previous studies, a retrospective study where we studied restenosis rates of long lesions below the knee treated with noncoated balloons, that restenosis rate is very high, and it comes very early. We have seen restenosis of 70% after just 3 months, and this has been confirmed by other study groups. This is important for patients because many patients with CLI and wounds are not healed after 3 months, so the restenosis occurs in a timeframe where wounds are not healed, and if the artery closes down again before the wound is healed, of course this has a negative effect on time to healing and rate of healing. Therefore when we looked at the DEB, we were looking for 3-month restenosis rates, and we found much lower restenosis of just 27% for long lesions with mean lesion length of 17 cm to 18 cm, and that is clearly completely different from a 70% restenosis rate.
Q: What were the objectives of the study?
A: These results differed from other studies – there are two other studies out, one is by Dr. Liistro from Italy, which is a single-center randomized trial. Ours was a retrospective analysis of a registry and comparison to historical data. So this study from Dr. Liistro also showed benefit for DEBs compared to noncoated balloons for lesions that are slightly shorter, for lesions typically found in patients with CLI, however he saw a difference out to 1 year. I had not yet dared to believe that the patency of these lesions treated with DEBs would last this long. But it was actually very encouraging to see results sustained for 1 year.
Then came the IN.PACT DEEP trial initiated by Medtronic, a multicenter trial where after a year there was no difference seen in terms of patency or late lumen loss, no benefit seen for the DEB compared to the noncoated balloon.
There have been different attempts to explain why this multicenter trial failed. We learned after these results were published that the manufacturing of this DEB could have been better because the DEB for below-the-knee arteries from Medtronic was first folded and then coated, which is different from the balloon for the SFA where the balloon is first coated and then folded. Of course we can also imagine that technique will improve over time. Nevertheless we saw differences; if you knew the drug was not well coated on the balloon, you knew how to work with this balloon – meaning thorough predilation, move the drug-eluting balloon quickly, and inflate it quickly so the drug is not lost to the periphery. These differences were also demonstrated by Dr. Liistro’s study.
Other attempts to explain why there was no benefit seen in the multicenter trial is that the lesions treated were much more benign than the lesions we treated and that Dr. Liistro treated. They were much shorter in the multicenter trial. The rate of total occlusion was much lower. Those lesions treated in the multicenter trial do not look like typical CLI lesions, which are long lesions with a high rate of total occlusion.
These are theories; we need more trials with better balloons and better technology. And there is still the hope that those results that I and Dr. Liistro have seen will be confirmed in the future.
Q: How will these results and these devices affect future decision making for vascular clinicians?
A: If we can prove that patency is better with DEBs compared to noncoated balloons, this will affect decision making. The bar for using this kind of balloon in long lesions in CLI patients should not be set too high. We don’t think that we can lower the amputation rate with this treatment option because standard balloon treatment for long lesions already gives us good results and we have registries with excellent results that are hard to beat with new results and new technologies. But the problem for these patients is the TLR rate is very high when you use noncoated balloons. Because of that restenosis rate which comes early in the course, a considerable number of those patients need repeat treatment. It could be a goal for DEBs to lower the need for repeat interventions. These are older patients, fragile patients, and we really want to try to treat them once and not two or three times during the healing of their wounds.
Q: Are there other studies that should be done, other data collected?
A: We have to continue with DEB treatment below the knee and with other drug-eluting devices like drug-eluting stents. It has been shown nicely already that besides lowering the restenosis rate you can achieve better clinical results in terms of TLR rate with drug-eluting technologies. Some trials have shown that you can reduce the amputation rate with these kinds of stents, so it would be nice to see these results with DEBs. With every DEB on the market we need a new study, because every DEB on the market is different – each has its own technology, its own carrier on the balloon. That can be a problem for the whole story of DEBs below the knee, because if the next trial of DEBs fails, we could lose support for this idea of taking DEBs into BTK arteries, and it might be just the effect of a balloon with technology that is not as good as it could be. That could be a problem in the future. But we have seen DEBs work nicely in these lesions. We hope to see comparative studies in the future comparing one balloon to the other.
Q: Is there anything else vascular clinicians should know about these results?
A: What was also noted in the multicenter IN.PACT DEEP trial was that the major amputation rate was higher with DEB than with noncoated balloon after 1 year. I don’t think that has to do with the DEB itself. You could think of perhaps embolization of paclitaxel into small arteries where patients had infections. From my understanding, that might cause problems after just 1 month compared to noncoated balloons. Why a higher amputation rate after 1 year would be caused by the paclitaxel is hard to understand. In fact, we collected data from our own institution which has treated more than 200 patients below the knee with the Medtronic DEB and we have seen after 1 year a major amputation rate of 3.9%, which is clearly lower than the 8.8% amputation rate of the IN.PACT DEEP and more like the major amputation rate of the noncoated balloon in the Medtronic trial. So, we haven’t seen any safety problems with that specific drug-eluting balloon.
Editor’s note: Andreij Schmidt, MD, is senior interventionalist at the University Clinic of Leipzig in Germany. Dr. Schmidt reports consultancy to, honoraria from, and travel reimbursement from Medtronic, Cook, Abbott, Bard, Cordis, and Boston Scientific.