Drug-Coated Balloon Approvals Mark ‘Sea Change’ for Treatment of PAD

A flurry of approval activity in the United States and Europe suggests that 2015, only just begun, may be shaping up to be the year of the drug-coated balloon (DCB).

In October 2014, Lutonix 035 (CR Bard) became the first FDA-approved DCB in the United States for the treatment of femoropopliteal artery disease. This was followed on January 5, 2015, by approval of the In.Pact Admiral DCB (Medtronic). Days later, Stellarex (Covidien), another DCB for the treatment of femoropopliteal lesions, became the latest of several to receive CE Mark approval in Europe. All 3 devices are paclitaxel-coated balloons but use different concentrations of the drug. Take Home: Drug-Coated Balloon Approvals Mark ‘Sea Change’ for Treatment of PAD

“I think most people in the field are very excited that the day has finally come that we have these therapies on the shelf, and I do think it’s going to be a ‘sea change’ in terms of what we do in the periphery,” William A. Gray, MD, of Columbia University Medical Center (New York, NY), told TCTMD in a telephone interview.

He added that data for both US-approved devices consistently demonstrated efficacy and ease of use despite some nuances in using the balloon.

Michael R. Jaff, DO, of Massachusetts General Hospital (Boston, MA), agreed. “These approvals represent an important next advance for US patients,” he said in a telephone interview with TCTMD. “It’s another option that allows us to avoid placing an implant in the artery.”

Women, Learning Curves, and Optimizing Angioplasty

The clinical trials of Lutonix and In.Pact compared the devices to conventional balloon angioplasty. Despite an overall sense of confidence in the safety of the devices, the FDA mandated as part of its Lutonix approval that the manufacturer conduct 2 postapproval studies. The first is a 5-year study of 657 patients to further monitor safety and effectiveness. The second is a randomized, single-blind, multicenter study that will assess the safety and effectiveness of the Lutonix DCB in women, due to a subgroup analysis that suggested their response was not as strong. This suggestion was not seen in the In.Pact dataset.

“This is really an interesting phenomenon, but it’s very hard to make heads or tails of it,” Dr. Jaff said. “We have seen other parallels like this before, such as the belief that outcomes of carotid stenting are not as good in women as in men. Then there have been opposite results where there was a suggestion in some studies that renal artery stenting results are as good if not better in women than in men. [The Lutonix data] were a curious, unexpected finding. The truth of the matter is the postapproval study is exactly the right thing to do,” he said, adding that there is no safety concern as far as using these devices in female patients.

Another issue for the new DCBs is whether there is a learning curve for operators. But according to Dr. Gray, the skill set needed to utilize them is not unique.

“One thing using the DCBs will do, however, is bring back the need to maximize your angioplasty, which is a lost art. This is needed to achieve a standalone balloon result with no metal prostheses,” he said.

Yet Dr. Jaff maintained that there “absolutely is a learning curve.” Although the technical component is not nearly as complex as carotid stenting, the biggest issue facing clinicians with these devices “is you have to make sure you deliver the balloon with the drug exactly [to] the target lesion and avoid the concept of geographic miss,” he said.

Christopher J. White, MD, of the Ochsner Heart and Vascular Institute (New Orleans, LA), concurred. “These devices are only as good as the operator who uses them,” he said in a telephone interview with TCTMD. “With the DCBs you cannot see where the drug gets deposited, so this is a big issue in terms of educating operators on proper use to maximize your success.”

‘Antiproliferative Era’

Dr. Gray noted that the approvals of the DCBs help clarify for interventionalists what they should be doing in terms of optimizing treatment in patients with femoropopliteal artery disease.

“Prior to availability of these balloons, we had atherectomy and lasers and various types of stents. But because the data were not clear that one of these was better than the other, it made it difficult to choose the ideal default strategy,” he said. “I would submit that we have entered into an antiproliferative era of SFA popliteal intervention, and it would be hard for me at this point to imagine a patient in whom I don’t offer some form of antiproliferative agent during an intervention.”

Dr. Gray maintained that the DCBs “will almost certainly be first-line therapy moving forward and drug-coated stents will be there in case you need a mechanical scaffolding that the DCBs can’t provide.

“Transformational is a strong word,” he added, “but I think when we look back on this, it will be considered a transformational event that these balloons have been made available because it unifies the approach.”

Dr. Jaff observed that among clinicians who are of the opinion that “less implant is better” when treating these lesions, “the DCB approach will be a natural transition.”

He added that DCBs are likely to follow the path of other novel devices throughout the cardiovascular system. “You’ll have the first wave—generation one—and then you will see improvements in drug coating, maybe different drugs that are more effective when delivered to the target area. Then in a few years we’ll see the second generation. The advantage of all this is that it puts price pressure on the system so that these devices become more affordable down the line.”

The Wild Card

But Dr. White asserted that cost is the wild card in the equation, presenting a potential obstacle to adoption. He noted that this has been the same barrier to widespread use of the drug-coated Zilver stent, which received FDA approval in 2012 for treatment of SFA disease.

“With that stent, we choose patients carefully who we think will benefit because it’s at a premium compared with other stents we could use,” he said. “Many of us thought the drug-coated stents would completely replace uncoated stents in this arena as they did in the coronaries. But that didn’t happen. So, I’m pretty sure it won’t happen with DCBs for the legs either. The cost benefit is going to have to be demonstrated in order for these to be commercially successful and available to patients.”

The true test may be time, Dr. White observed. “This problem of higher costs was seen when DES first came on the market. Today we are essentially paying the same price for a DES that we were paying for a BMS 5 or 6 years ago. As long as there is competition, we would expect prices to come down and even the playing field somewhat over time.” He estimated that eventually DCBs may account for 40-70% of the market for treating peripheral lesions.




Sources:1. US Food and Drug Administration. FDA approves first drug-coated angioplasty balloon catheter to treat vascular disease [press release]. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm418455.htm. Published October 10, 2014. Accessed January 16, 2015.
2. Medtronic. Medtronic Drug-Coated Balloon Receives FDA Approval for Treating Peripheral Artery Disease in Upper Leg [press release]. http://newsroom.medtronic.com/phoenix.zhtml?c=251324&p=irol-newsArticle&ID=2002957. Published January 5, 2015. Accessed January 16, 2015.
3. Covidien. Covidien’s Stellarex Drug-Coated Angioplasty Balloon Receives CE Mark to Treat Peripheral Arterial Disease Patients [press release]. http://www.covidien.com/investor/phoenix.zhtml?c=207592&p=irol-newsArticle&id=2005240. Published January 8, 2015. Accessed January 16, 2015.
4. Zacks.com. Covidien's (COV) Stellarex DCB Gets CE Mark Approval. http://www.zacks.com/stock/news/159931/covidiens-cov-stellarex-dcb-gets-ce-mark-approval. Published January 9, 2015. Accessed January 16, 2015.




  • Dr. Gray reports serving as a consultant for Medtronic.
  • Dr. Jaff reports serving as an uncompensated advisor for Medtronic.
  • Dr. White is on the scientific advisory board for Lutonix and served as an investigator for the clinical trial.

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