ILLUMENATE: Low-Dose DCB Bests Angioplasty Alone in Complex Patients With SFA/Popliteal Lesions

WASHINGTON, DC—A third drug-coated balloon (DCB) appears to be headed for the US market following positive trial results for the treatment of superficial femoral and/or popliteal artery lesions in a varied patient population, including many who have typically been considered challenging for this type of intervention. One-year results from the US-based, multicenter ILLUMENATE Pivotal IDE trial presented at TCT 2016 last week demonstrate the efficacy of the technology in women and in patients with severe calcium, diabetes, chronic kidney disease, and small vessels.

The study’s presenter, Sean Lyden, MD (Cleveland Clinic, Cleveland, OH), said the results reaffirm prior data on the same DCB (Stellarex, Spectranetics), including a first-in-human trial and a European randomized trial.

While Lyden was speaking to the media prior to his presentation, Spectranetics filed for premarket Food and Drug Administration approval. In a press release, the company said they anticipate that the DCB will hit the US market in the second half of 2017.

DCB Outperforms Balloon Angioplasty

The ILLUMENATE Pivotal IDE trial compared the paclitaxel DCB (n = 200) with standard balloon angioplasty (n = 100) in patients with arterial disease in the SFA and/or popliteal arteries. All patients were Rutherford class 2-4 and had at least one patent run-off vessel below the knee. They had a wide range of lesion lengths, measuring from 3 to 18 cm. In his presentation, Lyden noted that more than 40% of patients in both study arms had severe calcification, and about one-third had 0-1 patent run-off vessels.

All patients had successful predilatation, which occurred at an average of over 3 and a half minutes. Lyden said researchers have learned this step is important, noting that “long, slow inflations make sense.” The rate of bailout stenting was equivalent at 6% in both arms.

The DCB outperformed angioplasty for the primary safety endpoint of freedom from device- and procedure-related death through 30 days and freedom from target limb major amputation and clinically driven TLR through 1 year (92.1% vs 83.2%; P = 0.001). Additionally, there were fewer major adverse events with the DCB, driven by the difference in clinically driven TLR (7.9% vs 16.8%). At 12 months, freedom from clinically driven TLR was 93.6% for the DCB and 87.3% with angioplasty alone.

The primary effectiveness endpoint—the absence of restenosis and freedom from clinically driven TLR through 12 months—also was higher with the DCB (76.3% vs 57.6%; P = 0.003).

There were no differences between the two groups for secondary endpoints of ankle-brachial index, improvements in Rutherford classification, and improvement in 6-minute walk test. The DCB group, however, required about half the number of reinterventions as the angioplasty arm and had a primary patency rate at 1 year of 82.3% (vs 70.9% for angioplasty).

Off to the Races

Noting that Stellarex is “the third in a three-horse race,” William Gray, MD (Main Line Health/Lankenau Heart Institute, Wynnewood, PA), said in the press conference that the efficacy outcomes look to be “in rough keeping” with those of the other two DCBs on the market—Lutonix (Bard) and IN.PACT Admiral (Medtronic)—although he cautioned people to “stay tuned” for outliers and possible differences that may emerge.

Gray added that he was struck by how well the percutaneous transluminal angioplasty (PTA) group in the ILLUMENATE trial did overall, observing that the patency rate of that group was higher than what has been seen in the other DCB versus PTA trials. After Lyden’s presentation in the Main Arena, Gray further noted that the low dose of the Stellarex DCB (2 µg/mm2) makes it more similar to Lutonix than to IN.PACT Admiral.

Session panelist Sahil A. Parikh, MD (Case Western Reserve University School of Medicine, Cleveland, OH), said his “gestalt” was that despite the lower dose, the fact that the DCB did well in such complex patients speaks toward its potential clinical application.

Gray added that future research on the three DCBs will likely compare them against each other to attempt to tease out differences, since randomization to PTA is “going to be very difficult from an ethical standpoint” now that such robust data on each in comparison to PTA exist.

As for their position in relation to the standard of care for these types of lesions, Gray said the patterns of use of the DCBs in the last 2 years across the United States attest to their increasing acceptance among operators.

D. Christopher Metzger, MD (Wellmont CVA Heart Institute, Kingsport, TN), also speaking in the press conference, agreed, saying the DCBs are becoming more of a frontline therapy now than when they first appeared on the market 2 years ago in part because of the emerging durability data, as well as the cost pass-through reimbursement for hospitals.