Using drug-coated balloons to open clogged arteries is a new technology. It combines the advantages of angioplasty balloons and drug-releasing stents while offering fewer risks.
In the past few years, the innovation of using drug-coated stents has led to a drastic reduction of restenosis (a re-narrowing of the blood vessel) compared to bare metal stents, but 5 to 10 percent of patients with stents implanted are still in need of redoing the procedure.
In the new approach of using a balloon coated with a drug, a stent is not used at all.
The balloon is inflated in the artery for a short period (30 seconds or a little longer) where it releases a drug that stops the cells from building up and clogging the arteries over time. The drug released is zotarolimus or paclitaxel, which is absorbed into the tissue. After the medication has been released, the balloon is taken out and no hardware is left behind.
A new MIT study reveals what happens. When the drug is released, some of it sticks to the lining of the blood vessels. Over time, that drug is slowly released back into the tissue, so that way the drug's effects last much longer than the initial 30-second release period.
Future studies may investigate how the blood flow affects drug delivery, which coating compositions work best, and how effective the different balloons are in different type of vessels.
Drug-coated balloons can be useful in three clinical areas.
Peripheral vascular disease is offering probably the best opportunity, since in the environment like the legs, constant movement can easily fracture a stent.
Difficult types of coronary arteries, like bifurcated and small vessels are also a promising area. Bifurcated vessels are the ones that divide into side branches. They are more challenging for an interventionalist doctor to handle, as stents currently are not made in a "Y" configuration.
In-stent restenosis is also a useful segment. Here the blockage occurs inside of a previously implanted stent. Cardiologists are not too keen on putting another layer of metal into a blocked bare-metal or drug-eluting stent, particularly in an area with side branches. Implanting a new drug-coated stent inside of an existing one has been associated with re-blockage rates as high as 43 percent. Several recent studies have shown a substantial improvement in that percentage if paclitaxel-eluting balloons were used.
It is approved for the treatment of narrowed arteries in a variety of locations in the body, including the renal, iliac, iliofemoral, femoral, popliteal and infrapopliteal arteries. It features a hydrophilic (water friendly) coating, and features fast deflation, which may shorten procedure time.
Dr. Juan Pablo Zambrano, director of cardiovascular medicine at Jackson South Community Hospital in Miami said:
"Vascular specialists have been eagerly awaiting the Pacific Plus PTA catheter. The device`s ease of deliverability and various shaft lengths provide us with a flexible solution for both straightforward and complex cases."
Separately, Medtronic, encouraged by robust clinical data from the IN.PACT Admiral drug-eluting balloon trial, decided to submit the first part of its FDA application during the summer for a drug-coated balloon to treat hardening of the arteries in the upper leg. If approved, plans call for a late 2015 launch.
The ongoing global IN.PACT clinical program is a major undertaking. It includes 29 studies involving more than 4,600 patients at approximately 230 sites worldwide, which include both company-sponsored and physician-initiated studies.
The trials investigate drug-eluting balloons for the treatment of arterial disease in a wide variety of vessel beds.
IN.PACT Admiral uses a drug called FreePac for coating. It is a mixture of paclitaxel and urea, designed to help make the drug absorb better into the vessel wall. The balloon is for treating peripheral artery disease in the SFA (superficial femoral artery), which runs from the groin to the knee.
As a result of its location, the SFA experiences a variety of torsion and compression forces that pose challenges for the use of metallic stents.
The IN.PACT line has had CE mark status since 2008 but remains investigational in the U.S.
In May, Medtronic presented one-year data from an Italian multicenter randomized controlled trial of the IN.PACT Falcon drug-coated balloon.
The BELLO study enrolled 182 patients across 15 hospitals in Italy to compare the safety and effectiveness of two medical devices: Medtronic's IN.PACT Falcon drug-coated balloon and the Taxus drug-coated stent from Boston Scientific Corp (NYSE:BSX).
At six months, the BELLO study favored patients treated with the drug-coated balloon. The study met its primary endpoint, late lumen loss (narrowing of the blood vessel) at six months, with statistical significance showing superiority of the drug-coated balloon over the drug-eluting stent.
The Medtronic IN.PACT Falcon drug-eluting balloon received the CE mark in 2009 and is available in many countries around the world. It is not commercially available in the United States.
Other companies are also active getting into the business.
Biosensors International Group, Ltd., a Singaporean company, has licensed drug-coated balloon technology from Eurocor GmbH, a subsidiary of Indian company Opto Circuits.
The deal included three products and their patents: BioStream; BioPath 014; and BioPath 035.
BioStream is for use in coronary arteries; the two BioPath balloons have been optimized for the treatment of patients with peripheral arterial disease. BioPath 035 is intended for peripheral intervention above the knee and BioPath 014 for infrapopliteal intervention below the knee. All three products have paclitaxel coating.
Separately, the German company B. Braun Melsungen has run clinical trials in China. B. Braun's SeQuent Please drug-coated balloon catheter is intended to deliver drugs directly to the lesion during angioplasty. A paclitaxel-coated balloon worked just as well as a paclitaxel-coated stent, the Chinese trial showed.
Medtronic's fourth quarter (which ended April 26, 2013), total revenues were $4.5 billion, up 5 percent year-over-year.
The CRDM (Cardiac Rhythm Disease Management) unit, which is part of the Cardiac and Vascular Group, produced $1.3 billion in revenue, an increase of 4 percent.
Sales of drug-eluting stents increased 22 percent, driven by broad worldwide gains in market share of the Resolute Integrity drug-coated stent.
Regarding the acceptance of the drug-coated balloons, Dr. Pascal Meier of the University College London, UK, counted himself among the naysayers, until he reviewed the data from a meta-analysis published earlier this year. He said:
"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. So it's more believable that there is a long-term effect."
The global market for interventional cardiology devices was estimated at $15.8 billion in 2011 and is expected to grow at a 6.8% from 2012 to 2018 to reach an estimated value of $25.2 billion in 2018. This is obviously a large market and even if a small segment converts drug-coated balloons from stents, it will amount to a substantial figure.
Can medicated balloons from Medtronic and others replace stents?
Possibly, eventually. First, they have to perform well in the clinic, after approvals, in segments where stents are not available or difficult to apply. If they do, gradually they will take over areas where stents are prevalent now. It is going to be a race of technologies for awhile, beneficial to all participants: patients, doctors and investors.