PARIS, France—In the latest setback for an intriguing technology, a paclitaxel-eluting balloon combined with a bare-metal stent (BMS) failed to improve outcomes vs. a BMS or drug-eluting stent (DES) alone in treating bifurcation lesions, according to results presented during a late-breaking trial session May 25 at EuroPCR 2010.

For the Drug-Eluting Balloon In Bifurcation Trial (DEBIUT), researchers led by Pieter R. Stella, MD, PhD, of University Medical Center Utrecht (Utrecht, the Netherlands), randomized 120 patients with coronary bifurcation lesions to 3 treatment arms, all involving provisional stenting and final kissing balloon inflation:

• Angioplasty using only a BMS
• Angioplasty with drug-eluting balloon inflation and a BMS
• Angioplasty using only a paclitaxel-eluting DES

The stent platform used in each arm was the Liberté (Boston Scientific, Natick, MA). The potential benefits of the Dior paclitaxel-eluting balloon (Eurocor, Bonn, Germany), Dr. Stella noted, include local drug delivery over a short period of time, avoidance of chronic inflammation due to absence of polymers, and avoidance of multiple layers of metal.

In particular, DEBIUT researchers wanted to see whether the drug-eluting balloon could help achieve better side branch patency while reducing the need for side branch stenting and for prolonged dual antiplatelet therapy. In the BMS and drug-eluting balloon arms, only 3 months of dual antiplatelet therapy were prescribed.

In DEBIUT, patients in all 3 arms were well matched in terms of baseline demographics and procedural characteristics including fluoroscopy time and total procedure time. Procedural success was 100% in each arm.

Six-month angiographic follow-up, though, showed no difference among the treatment groups for the primary endpoint of late lumen loss in the main branch or side branch (table 1).

Table 1. Late Lumen Loss at 6-Month Follow-Up^a

^a P = NS for all comparisons.

Nevertheless, Dr. Stella pointed out that the numerical reduction in late loss between the balloon and BMS arms, though not statistically significant, was encouraging, especially in the side branch, where the rate was 50% lower with the Dior balloon. Also, binary restenosis was lower with the paclitaxel-eluting balloon vs. BMS in the proximal main branch (0 vs. 3.0%), the distal main branch (9.4% vs. 18.2%), and the side branch (6.3% vs. 12.1%), though these differences were also not statistically significant.

All other angiographic outcomes were equivalent in each arm in the main and side branches.

In terms of clinical outcomes, there were also no differences among any of the treatment arms at 6 months, although drug-eluting balloon patients showed numerical reductions in MACE and TLR compared with BMS patients (Table 2).

Table 2. Clinical Outcomes at 6-Month Follow-Up^a

^a P = NS for all comparisons.

“Due to the unanticipated good results in the [BMS] arm, the primary endpoint was not reached, and because of the lack of power, the 50% reduction in side-branch late loss was not statistically significant,” Dr. Stella said. “However, there are strong trends which show a favorable outcome combining [the drug-eluting balloon] with a BMS in the main branch and using a [drug-eluting balloon] in the side branch especially with regards to late loss and binary restenosis rates.”

He added that limiting dual antiplatelet therapy to 3 months in the BMS plus paclitaxel-eluting-balloon patients seemed safe, with no occurrences of stent thrombosis.

“Certainly, a larger randomized study is warranted between the drug-eluting balloon and a cobalt-chromium stent vs. a DES plus plain old balloon angioplasty,” Dr. Stella said.

The Latest Blow

It has been an uneven road for drug-eluting balloon technology. At the 2009 American Heart Association Scientific Sessions, researchers presented results from the PEPCAD III trial showing that the Sequent Please paclitaxel-eluting balloon combined with a BMS (B. Braun Melsungen AG, Vascular Systems, Berlin, Germany) failed to reach noninferiority against a sirolimus-eluting stent in treating de novo coronary lesions and actually showed worse safety outcomes.

And at EuroPCR 2009, researchers reported interim results from the Piccoleto trial, which showed no improvement in percent diameter stenosis in patients with small coronary vessels treated with the Dior balloon vs. Taxus stents. The trial was halted early when the drug-eluting balloon could not prove noninferiority.

But the news has not been all bad. The year before, at EuroPCR 2008, researchers presented data from the PEPCAD I trial showing that the Sequent Please achieved low rates of restenosis and MACE in a cohort with small-vessel coronary disease.

Despite Outcome, Call for a Larger Trial

Commenting on DEBIUT, Sigmund Silber, MD, of Müller Hospital Munich (Munich, Germany), noted that the study was well conducted, using provisional T stenting as a default with stenting of the side branch in less than 8% of cases. In addition, there were no geographic misses with the drug-eluting balloon.

However, there was a mixture of 2 different generations of the Dior balloon used, “and angiographic follow-up was not as high as I would have liked (91.5%),” he added. “The primary endpoint was not reached, maybe because the late loss of the Liberté stent was lower than expected, maybe due to overstretching of the proximal main branch by the kissing balloon technique.”

Nevertheless, despite the outcome of the trial, “I agree with Pieter Stella that it is time now for a major randomized trial,” Dr. Silber said. “But it should be powered for a primary clinical endpoint with no routine angiographic follow-up, comparing 2 drug-eluting balloons with a bare stent plus a dedicated bifurcation DES, and maybe if we choose a noninferiority design, the chances of getting a positive trial are higher.”

Disclosures:

• Dr. Stella reports serving on the advisory board of Eurocor.
• Dr. Silber reports receiving grant support or speakers fees, or serving as a consultant or an advisory board member for Abbott, Biotronik, Boston Scientific, Bristol-Myers Squibb, Cordis, Daiichi-Sankyo, Eli Lilly, Eurocor, Medtronic, Orbus Neich, Pfizer, sanofi-aventis, Terumo, and The Medicines Company.

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