Shelley Wood

May 29, 2013

PARIS, France — Drug-eluting balloons are "here to stay for the long run," and it's time the US guidelines offered some direction for interventional cardiologists seeking to understand the role for these devices in in-stent restenosis (ISR), experts argued at last week's EuroPCR 2013 meeting. Others, however, pointed to conflicting trial results, publication bias, and problems with the existing technology.

Speaking during a Friday session, Dr Christoph K Naber (Contilia Heart and Vascular Center, Essen, Germany) pointed out that the European Society of Cardiology deals with drug-eluting balloons in its 2010 guidelines (a IIa [B] recommendation for restenosis of a prior bare-metal stent), and both Germany and Italy have released position statements on the technology. German guidance, for example, concluded in 2011 that while clinical end points are "missing," positive data from randomized controlled trials with angiographic end points have been published supporting the use of drug-coated balloons for the treatment of in-stent restenosis. The American College of Cardiology/American Heart Association 2011 guidelines, however, state only that "drug-eluting balloons were considered for formal evaluation, but there were insufficient data to formulate any formal recommendations."

Three Clinical Realms for Drug-Eluting Balloons

There are three areas in which drug-eluting balloons have been studied and used in clinical practice. Their role is perhaps best accepted in peripheral vascular disease, in part because drug-eluting stents that are so well-established in coronary disease can fracture in high-mobility vessels. The second area is de novo coronary artery disease, where balloons have had the greatest difficultly in proving they can match the results of drug-eluting stents; research here has focused on bifurcations and small vessels. The third frontier is ISR, where many of the experts speaking during a dedicated EuroPCR session said they believe drug-eluting balloons should play a key role, although conclusive evidence has been lacking.

Naber concluded that in light of the existing data, "all current guidelines should clearly mention drug-coated balloons as a relevant treatment option for bare-metal-stent ISR." Moreover, new guidelines should address the role of this technology in the setting of drug-eluting stent restenosis and treatment of de novo lesions.

Dr Bernardo Cortese (Azienda Ospedaliera Fatebenefratelli, Milan, Italy), agreed with Naber.

"I believe the guidelines should say: we have had this discussion, we have these devices, we can say there are not enough good data, but we can make a recommendation," Cortese argued. "Guidelines are not just evaluations of existing data, they are also expert consensus; otherwise, we wouldn't need the expert comment."

However, Dr Ron Waksman (Washington Hospital, DC), who also spoke during the session, argued that the US guidelines were right to hold off on recommendations. There are too many unknowns with drug-eluting balloons, he noted. These include the challenges of effectively and specifically delivering the right amount of drug to the exact length of lesion, which drug and dose to use, and how to manage dissections and recoil (if the putative aim of balloon-delivered treatment is to avoid stent placement).

And all trials to date have included small numbers of patients from a small number of centers, some have never been published, many have used devices that are not commercially available, and none have been carried out in the US, Waksman noted. "You cannot make guidelines if you only have small pieces of studies of less than 100 patients to draw on."

All Paclitaxel, No -Limus

All of the devices approved in Europe (Italy, for example, has access to eight drug-eluting balloons) elute paclitaxel, an agent that has been left in the dust in the drug-eluting-stent world as the -limus agents have taken over. The drug-coated balloon developers moved forward with paclitaxel, in part, because its lipophilic profile made it easier to deliver consistently to the tissue, while -limus drugs tended to wash away in the bloodstream.

It's also just "the economy," Dr Juan F Granada (Columbia University, New York, NY) pointed out. Limus drugs are more expensive than paclitaxel, particularly because they require new carrier agents to control their delivery into the vessel wall. "I believe companies are just taking the low-hanging fruit first [by using paclitaxel], but I'm sure -limus options will come. It will just take time."

Granada also predicted that, despite the need for better trials and new technology, drug-coated balloons remain one of the most versatile technological developments in interventional cardiology and "are here to stay for the long run."

Other barriers include cost and, less tangibly, physician mind-set, session cochair Dr Pascal Meier (University College London, UK) explained to heartwire . In the UK, for example, drug-eluting balloons actually cost more than drug-eluting stents, so the former are seldom used, even though physicians may balk at the notion of putting another layer of metal into a reoccluded bare-metal or drug-eluting stent, particularly in an area with side branches.

Cardiologists: Open Your Minds

But many cardiologists may also have presumed that drug-eluting balloons would never successfully compete with new drug-eluting stents in de novo lesions, and therefore they remain niche devices for use in peripheral vascular disease. And that, says Meier, discounts the need for solutions to treat in-stent restenosis, which has declined but not disappeared in the drug-eluting-stent era.

"With drug-eluting stents, the rate of ISR is still about 5% to10%, but higher in diabetics, small vessels, and bifurcations," Meier said.

Meier counted himself among the naysayers, until he reviewed the data from a meta-analysis published earlier this year. That analysis concluded that drug-eluting balloons were better than both bare-metal stents or plain old balloon angioplasty for treating in-stent restenosis.

"I've been a skeptic for a long time. In the first trials, I didn't believe that a short inflation of a balloon would have a sufficiently prolonged effect on the lesion, and with the first-generation balloons, that probably was the case--the drug was washed away."

Newer-generation balloons include a carrier designed to ensure that the drug remains attached to the balloon until it has been inflated and facilitates penetration into the tissue. Studies show that paclitaxel remains in the tissue for days or weeks, even months, he said. "So it's more believable that there is a long-term effect."

Meier reported no conflicts of interest. Cortese reported no conflicts of interest related to his drug-eluting-balloon presentation. Granada disclosed receiving grant/research support from Boston Scientific, Abbott, Medrad, and CircuLite; consulting fees from Medrad and Thoratec; he holds major stock/equity in VNT. Naber disclosed grant research support from Abbott, Biosensors, Biotronik, Claret, Stentys; consulting fees from Abbott, Biosensors, Biotronik, Edwards, Eurodor, Stentys, Terumo, Tryton, Medtronic, Meril Life Science, Siemens; and "other financial benefits" from Cordis, B Braun, and Boston Scientific. Waksman disclosed receiving grant/research support from Volcano, Medtronic Vascular, Abbott Vascular, and Boston Scientific and receiving consulting fees/honoraria from Biotronik, Medtronic, Abbott, Boston Scientific, Lilly/Daiichi, and AstraZeneca.

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