Endovascular Treatment of Fem-Pop Lesions: Where Do We Stand After IN.PACT SFA?

New 24-month results from the IN.PACT SFA trial provide further encouragement about the utility of a new drug-coated balloon (DCB) relative to standard angioplasty. But how much closer is the cardiovascular community to having a clear standard of care for femoropopliteal lesions?

Not as close as we need to be. So argues Mehdi H. Shishehbor, DO, MPH, PhD, in an invited editorial accompanying the IN.PACT SFA study report in Journal of the American College of Cardiology.

“The authors should be congratulated for these outstanding results in moderately long lesions,” writes Dr. Shishehbor, Director of Endovascular Services at Cleveland Clinic. “However, how generalizable are these results?” he adds, noting that there remain many options for the endovascular treatment of femoropopliteal lesions, with few head-to-head randomized comparisons between technologies.

IN.PACT SFA at a glance

In brief, the randomized IN.PACT SFA trial compared the Admiral DCB (Medtronic Endovascular) with standard angioplasty in 331 patients with Rutherford class 2-4 femoropopliteal lesions (mean lesion lenth, 8.94 cm).

DCB therapy was associated with significantly higher rates of patency at 24 months compared with angioplasty (78.9 percent vs. 50.1 percent) as well as significantly lower rates of clinically driven target lesion revascularization (9.1 percent vs. 28.3 percent).

Other notable findings:

• Functional improvement was similar between the two groups, although it was achieved with a higher number of reinterventions in the angioplasty arm.
• Rates of bailout stenting and complications were low in both groups.

Points worth noting about the study

In his assessment of IN.PACT SFA, Dr. Shishehbor points out the following:

• Because patients were randomized after balloon predilatation and because the number of patients excluded because of failed angioplasty is uncertain, the general applicability of DCB intervention “in all comers” is unknown. “Hence, DCB should likely be used after predilatation with an undersized balloon,” he writes.
• More than 95 percent of lesions in the study were shorter than 10 to 12 cm, which leaves the safety and efficacy of DCB therapy for moderate to long lesions unknown — a limitation that applies to most studies of stents as well.
• The IN.PACT SFA researchers’ use of core lab adjudication for all ultrasound- and clinically driven target lesion revascularization makes their findings on revascularization rates particularly trustworthy.

Despite the study’s strengths, Dr. Shishehbor notes that additional questions are left unanswered:

• What is the pattern of restenosis or frequency of occlusion following DCB therapy, and what predicts restenosis or occlusion?
• Were there differences in clinical presentation at the time of target lesion revascularization between the two groups?

So many options, so little guidance

Beyond these study-specific questions, Dr. Shishehbor catalogs uncertainties stemming from the “treatment conundrum” brought about by the burgeoning number of options now available to treat femoropopliteal lesions. These include nitinol self-expanding stents, drug-eluting stents, wire-interwoven nitinol stents, covered stents and now DCBs — not to mention atherectomy or cutting balloon angioplasty.

Dr. Shishehbor writes that it’s difficult even to assess the two DCBs commercially available in the U.S. — the Admiral DCB and Bard’s Lutonix® 035 DCB — against one another at this point. They differ in paclitaxel dose, excipient used, coating technology and balloon materials. Moreover, there are no head-to-head comparison data between the two DCBs, and their pivotal trials for FDA approval defined primary patency in different ways. “An important question remains,” Dr. Shishehbor observes. “Is this a class effect or are there differences between the two currently approved devices?”

Some knowns among the unknowns

Despite the lingering questions, Dr. Shishehbor notes that IN.PACT SFA and other DCB studies to date have clarified at least a few important points:

• For moderate-length femoropopliteal lesions, DCB therapy appears to produce patency comparable to that achieved with most stents at two years.
• Plain balloon angioplasty appears to be clinically inadequate for femoropopliteal lesions and should rarely be used as stand-alone therapy.
• DCB therapy will have a significant impact on patient care and perhaps on outcomes.

“[DCB] technology has received a warm welcome from most physicians,” he writes, expressing hope that global registries for both of the commercially available DCBs will yield important insights to guide clinicians in the future. He identifies several priority research questions for both DCBs: How they perform in the setting of severe calcification, how they perform against long lesions (> 20 cm) and whether they are effective in patients with Rutherford class 5 and 6 lesions.

In the meantime, Dr. Shishehbor concludes, “we must encourage and demand head-to-head comparisons of old, new and future technologies so that the safest, most efficacious and cost-effective devices are identified.”

Join us April 17-19, 2016, at the Cleveland Clinic Masters’ Approach to Critical Limb Ischemia Symposium.