Optimal endovascular strategy for infrapopliteal lesions remains unclear

Although drug-coated balloons show some promise as a treatment option for patients with infrapopliteal lesions, questions linger about their efficacy in this population, experts noted during a debate at TCT 2017.

“The topic is controversial, but I do believe there is hope for the future,” Bryan T. Fisher Sr., MD, chief of vascular surgery and co-director of the limb Preservation Center at TriStar Centennial Medical Center, Nashville, Tennessee, said.

However, some disappointing data have spurred doubts in many operators, according to Robert A. Lookstein, MD, MHCDL, FSIR, FAHA, FSVM, professor of radiology and surgery and vice chair and system chief of interventional services at Mount Sinai Health System, New York.

“DCBs have, to date, failed to demonstrate any clinical benefit despite improved angiographic outcomes and it is unlikely that DCB will demonstrate clinical benefit for below-the-knee lesions in the foreseeable future,” he said.

Unique challenges

Fisher, who was charged with discussing the potential of DCBs for treatment of infrapopliteal lesions, noted that even though DCBs have clearly shown a benefit when compared with plain balloon angioplasty in above-the-knee disease, the level of success in below-the-knee disease has been discouraging. However, he pointed out that the lack of success may be due in part to challenges that are unique to below-the-knee disease.

For instance, below-the-knee lesions tend to be vastly different in that they are often complex, long, heavily calcified and have intimal calcification. The ability to successfully treat these lesions is also hampered by their distance from the initial access site. Fisher noted that operators can compensate for this issue by using retrograde pedal access but pointed out that most operators do not regularly perform this particular technique.

Moreover, in its current form, most operators would not argue that DCB alone would be best for treating equally complex lesions in the coronary vessels, which are significantly shorter, so the same would likely hold true for lesions in these longer vessels, he noted.

“We have to become better at defining our goals and what we are trying to accomplish,” Fisher said. “Is it realistic to think that with the current state-of-the-art that DCB for lesions below the knee is going to provide long-term patency? I would say not ... We also must remember that limb salvage correlates very poorly to primary patency.”

Other issues include high restenosis rates, a tighter margin of error and increased technical challenges in the small vessels of the infrapopliteal vs. infrainguinal region, according to Fisher. The tibial vessels are also less understood because most operators are not performing the majority of their work below the knee, he noted.

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Current evidence

At present, there are some data that have demonstrated a trend toward promising results with DCB in below-the-knee lesions, including the Leipzig registry, DEBATE-BTK and DEBELLUM, according to Fisher. However, he noted that many of these studies showing benefit were conducted at a single center and lacked core lab evaluation.

One reason that DCBs may not have been as successful is the presence of calcium in these lesions, as it is likely a barrier to drug delivery, Fisher explained. He noted that in several of these studies, calcium was seen as a factor in the risk for restenosis and the subsequent success of the devices studied. Therefore, Fisher said, because calcium is known to be present in below-the-knee disease, vessel modification likely plays a huge role in treatment of these lesions.

In contrast, the first multicenter trial with core lab adjudication — IN.PACT DEEP — painted a different picture of DCBs in below-the-knee disease, according to Lookstein, who was tasked with discussing the lack of benefit of DCB in infrapopliteal lesions. The trial, which enrolled a real-world population with complex lesions, demonstrated no difference in efficacy endpoints with DCB vs. plain balloon angioplasty. These data were soon followed up by results from the BIOLUX P-II randomized trial that again showed no differences in outcomes between DCB and plain balloon angioplasty.

Currently, researchers and operators are awaiting answers from the ongoing Lutonix BTK trial, but Lookstein remains unsure if it will better inform treatment decisions.

“With IN.PACT DEEP and BIOLUX P-II, there are two strikes against DCB right now,” he said. “I was hoping Lutonix BTK would provide us with answers, but it has been difficult to enroll and has now been opened up to claudicants, so it is unlikely it will definitively define whether or not DCBs work in the below-the-knee segment ... If the trial is negative, it will be a third strike and industry will likely retreat from this space.”

Another way forward

In light of the negative results regarding the use of DCBs in infrapopliteal lesions, perhaps the data are not showing that DCB is not good enough but rather that plain balloon angioplasty is better than once thought, Lookstein noted. For example, he cited the NanoCross BTK study that showed 64% primary patency at 12 months with a dedicated below-the-knee balloon.

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“DCB has to be better than this, and I would argue that we haven’t seen that yet, so the objective to beat plain balloon angioplasty is perhaps more daunting than we had previously anticipated,” he said.

Lookstein also highlighted the potential benefits of using drug-eluting stents for treatment of lesions below the knee. He noted that there is a lot of strong evidence supporting DES use, including from the ACHILLES, YUKON and DESTINY trials, although the studies involved short lesions. However, not only do more recent trials such as PREVENT and DESTINY 2 demonstrate similar outcomes, results from IDEAS, although a single-center trial, comparing DES with DCB in long lesions favored DES. A Bayesian analysis also suggested that of all paradigms for the below-the-knee segment, DES is better than DCB in terms of freedom from restenosis, freedom from target lesion revascularization and limb amputation, according to Lookstein.

“There are several randomized trials showing clinical benefit with DES,” he said. “My humble argument is that we should probably reengineer DES to allow them to fit in the below-knee circulation and then we will have a true implant that has benefit in terms of primary patency and clinical benefit.”– by Melissa Foster

Reference:

Banerjee S, et al. Session IV. Optimal Treatment of SFA and Tibial Vessels: Balloons, Drugs, Scaffolds, and Beyond. Presented at: TCT Scientific Symposium; Oct. 29-Nov. 2, 2017; Denver.

Disclosures: Fisher reports he has received grant support or a research contract from Bard Medical and has received consultant fees, honoraria or is on the speaker’s bureau for Abbott Vascular, Cardiovascular Systems Inc. and Cordis. Lookstein reports he has received consultant fees, honoraria or is on the speaker’s bureau for Boston Scientific and Medtronic.