More Discouraging News for DCBs in Treatment of Infrapopliteal Lesions

One year after the pivotal IN.PACT DEEP trial failed to show superiority of a drug-coated balloon (DCB) over standard balloon angioplasty for below-the-knee revascularization, new data on a different DCB are similarly lackluster, according to a first-in-human study published in the October 2015 issue of JACC: Cardiovascular Interventions.

IN.PACT DEEP, published in the Journal of the American College of Cardiology last October, found similar rates of clinically driven TLR, late lumen loss, binary restenosis, and reocclusion in patients with critical limb ischemia (CLI) randomized to the IN.PACT Amphirion paclitaxel-eluting DCB (Medtronic; Santa Rosa, CA) or a standard uncoated balloon. The findings led to the DCB’s sponsor withdrawing it from the market.

For the new BIOLUX P-II study, investigators led by Thomas Zeller, MD, of Universitäts-Herzzentrum Freiburg-Bad Krozingen (Bad Krozingen, Germany), randomized 72 patients (79% men, 72.2% Rutherford class 5) with restenotic infrapopliteal lesions to the paclitaxel-coated Passeo-18 Lux DCB (n = 36; Biotronik AG, Buelach, Switzerland) or the uncoated Passeo-18 percutaneous transluminal angioplasty (PTA) balloon catheter (n = 36).

Baseline characteristics between groups were similar, with the exception the DCB-treated patients having fewer lesions without calcification (55.9% vs 81.6%; P = .018) and more lesions with moderate to severe calcifications (26.5% vs. 7.9%; P = .056).

No Real Differences

For 30-day major adverse events (primary safety endpoint; composite of all-cause mortality, major amputation of the target extremity, target lesion thrombosis, and TVR), there were no differences between the 2 balloon groups. These findings remained similar at 1 year. Rates of target lesion primary patency (primary performance endpoint) also were equivalent, with high patency loss in both groups at 6 months and 1 year (table 1).

Approximately one-quarter of patients in both groups underwent target extremity amputation by 1 year. Major amputation rates were low and similar for the DCB vs PTA (3.3% vs 5.6%; P = .631); all cases occurred in patients who were Rutherford class 5 at baseline, had diabetes, and presented with reference vessel diameter of ≤ 2.5 mm.  

According to Dr. Zeller and colleagues, many “unanswered questions” remain. More research is needed to answer questions regarding drug delivery to infrapopliteal lesions and the effect of angioplasty in this vascular territory, as well as to determine how additional imaging modalities might improve clinical outcomes and to aid in matching patients with the best therapy.

Much Ado About Patency

“Unfortunately for paclitaxel DEB, this study joins others in failing to meet criteria for superiority versus PTA alone for angiographic and hard clinical endpoints and supports the supposition of high restenosis rates but high limb salvage rates with plain old balloon angioplasty alone,” notes Thomas T. Tsai, MD, MSC, of Kaiser Permanente Colorado (Denver, CO), in an editorial accompanying the study. 

In a telephone interview with TCTMD, Krishna J. Rocha-Singh, MD, of the Prairie Heart Institute at St. John’s Hospital (Springfield, IL), senior investigator for IN.PACT DEEP, concurred. While more preclinical work is justified to better understand the infrapopliteal vascular territory, he said, if the currently-enrolling BTK trial also comes up negative, “people are going to start wondering what is going on.”

Drawing a parallel to what has happened in the field of renal denervation where results from smaller, single-center studies could not be replicated in larger, randomized studies, he said failure of BTK most likely will mean “we’re going to stop … and start looking at other means and methods of wound healing aside from just patency” in the treatment of CLI patients.

“Most of these patients just want to hold onto their legs and they want the wounds healed,” Dr. Rocha-Singh said. “Maybe at the end of the day, a good old balloon, for right now, has to be defined as the standard of care in association with good wound care.”

He also suggested that future endeavors might focus on adjunctive therapies such as the use of DCB and biologics, adding that pretreatment of the vessel might be an answer to removing barriers to paclitaxel and promoting patency.

According to William A. Gray, MD, of Columbia University Medical Center (New York, NY), while wound healing is paramount from a practical perspective, patency may actually be very important for the many patients whose wounds either do not heal or reform. Thus, he asserted to TCTMD in a telephone interview, it is still a relevant endpoint.

Despite BIOLUX P-II providing no advantage to the DCB, it is valuable in “that there was no safety signal,” Dr. Gray said. But he agreed that its results, coupled with those of IN.PACT DEEP, now call into question the single-center studies from Europe that showed greater efficacy of the now-defunct IN.PACT Amphirion compared with uncoated balloon.

“This is exactly why we do randomized, multicenter trials that are adjudicated,” he remarked. Improving on patency will pay off in terms of hard clinical outcomes in some patients, Dr. Gray predicted, “but in a trial format where you don’t know which patients to select, any benefit [of the DCB on patency] may be washed out by patients in whom it has less effect.”

Sources: 
1. Zeller T, Beschorner U, Pilger E, et al. Paclitaxel-coated balloon in infrapopliteal arteries. J Am Coll Cardiol Intv. 2015;8:1614-1622.
2. Tsai TT. Missing the forest for the trees? Drug-eluting balloon treatment for infrapopliteal disease [editorial]. J Am Coll Cardiol Intv. 2015;8:1623-1625. 

Disclosures:

• The study was sponsored by Biotronik AG. 
• Dr. Zeller reports relationships with multiple pharmaceutical and device companies.  
• Drs. Tsai and Gray report no relevant conflicts of interest. 
• Dr. Rocha-Singh reports serving as a consultant to Medtronic. 

Related Stories:

• Drug-Eluting Balloons Lower TLR in Diabetics with Critical Limb Ischemia
• Infrapopliteal Angioplasty Shows Long-term Promise for Critical Limb Ischemia
• Drug-Eluting Balloons Show ‘Impressive’ Results in Below-the-Knee Lesions