An Expert Interview With Dr. Julio Palmaz: Part II -- Drug-Eluting and "Interactive" Stents

May 13, 2004

Editor's Note:
In the second part of a 2-part interview, Dr. Julio Palmaz outlines the newer trends in stents and speculates on what the future may hold for this swiftly evolving area of medicine.

Julio Palmaz, MD, creator of the first commercially available stent, attended the recent 29th Annual Meeting of the Society of Interventional Radiology (SIR) in Phoenix, Arizona, where he was sat down with Medscape's Pippa Wysong to reflect upon the impact of his work on the specialty of endovascular interventions.

Dr. Palmaz is Stewart R. Reuter Professor and Chief of Cardiovascular and Interventional Radiology at the University of Texas Health Science Center in San Antonio, Texas.

(The first stent to be approved by the US Food and Drug Administration [FDA] was on display at the Smithsonian Institute in 2003 as part of Hispanic Heritage Month.)

Medscape: What was the original stent made of?

Dr. Palmaz: Stainless steel. That pretty much became the industry standard and is commonly used for other sorts of vascular implants. Next year it will probably be L-605, which is a chrome, cobalt, and tungsten alloy. It's a better material, is more radio-opaque, is equally corrosion-resistant, and is very strong.

Medscape: What would you say is the biggest improvement or change in stents in recent years?

Dr. Palmaz: The biggest advance in recent years has been the advent of the drug-eluting stent. In this instance, Johnson & Johnson has slowly taken the lead in the marketplace. They applied antiproliferative drugs to a stent, delivered through a polymer coating. The initial results in early trials were fantastic, and eventually their stent was approved for sale in 2003. The company was the sole supplier of the drug-eluting stent for almost a year until the new stent from Boston Scientific received FDA approval.

Medscape: Just how much of an improvement were the drug-eluting stents?

Dr. Palmaz: The drug-eluting stent introduced a totally new concept because restenosis had always been a problem associated with the use of stents. Even at the time of the STRESS and BENESTENT trials, where we were happy because we did better than balloons, the restenosis rates for stents was about 30% to 35%, while the restenosis rate with balloons was 50%. Although we saw some improvement, neither method was perfect. Restenosis has always been a limitation. Even today with state-of-the-art stents, the restenosis rates for plain, non-drug-eluting stents is around 15% to 20%. When you use the antiproliferative drugs in conjunction with stents, restenosis rates drop to somewhere between 5% and 10%. It meant that the single limitation of stents almost went away. Then the stent became the treatment of choice for coronary artery disease. Prior to combining the drug/stent approach, a patient might not get a stent because he had diabetes or because his vessels were too small. Today there's really no reason not to give that patient a stent. Drug-eluting stents do well in every patient subtype.

Medscape: At what point did the drug-eluting stents come to the fore?

Dr. Palmaz: They appeared 3 or 4 years ago. In both animal and clinical trials the results were staggering; there was a huge difference seen in restenosis rates. Today, at least for the coronary arteries, the feeling is that drug elusion is the way to go. There is no other reason than cost to not use a drug-eluting stent.

Medscape: Are there any limitations to these stents?

Dr. Palmaz: There are some concerns about things like heparin sensitivity reactions or delayed occlusions. Very few patients have those problems.

Medscape: How long does the drug stay in a drug-eluting stent?

Dr. Palmaz: The drug eludes away from the stent and is gone in about a month. There are some concerns about the polymer being the one that is actually producing some of the problems. A lot is known about metals, but not as much about polymers.

Medscape: What other sorts of ideas for stents are there?

Dr. Palmaz: When I was working with and developing balloon-expandable stents, there were other ideas being considered. Self-expanding stents is one example. This type of stent and other approaches have all been employed in areas in which certain types of stents are needed. In the coronaries, the balloon-expandable stents have remained the best choice. The self-expanding stent didn't work in the coronary arteries so they aren't used for that application.

Medscape: When is the self-expanding stent used -- for peripheral procedures?

Dr. Palmaz: Yes. There are several self-expanding stents. Overall, there are dozens of different stents for different uses.

Medscape: What are some of the advantages and disadvantages of different types of stents?

Dr. Palmaz: I worked my whole life with balloon-expandable stents, so I'll give you my biased opinion against it. The self-expanding stent has certain inherent advantages. The biggest advantage is that it can be used in vessels exposed to external pressure -- vessels that are superficial and can be deformed, such as the carotid or femoral artery. They're fine for those applications. Every time you place a stent in an area that can be compressed it's better to use the self-expanding stent simply because you can collapse it down, and if needed it can recoil back. It's very elastic. But in general, when you compare them on the same application where both are adequate, the balloon-expandable stent restenosis rates are better than the self-expanding stent. That's the reason why in critical applications, such as in the coronary or renal arteries, balloon-expandable stents have prevailed.

Medscape: Could you tell us a bit about the newer-generation stents?

Dr. Palmaz: My stent doesn't carry my name anymore. It's not called the Palmaz-Schatz anymore. The newest generations of stents have fancy names that sound like running shoes. The drug-eluting stent has a name of its own, CYPHER, but the one before that was called Bx-Velocity. The next generation will be called Steeple Chaser. When people ask me what the difference is between these and the original stent, I say, "The balloon-expandable stent in its original form was like the first radial tire. These are radial tires; they have different treads, but it's still a radial tire. " The principle is the same as with radial tires. They perform better because the design has been optimized. They are flexible along the longitudinal axis and they have better expandability.

Medscape: You must be amazed at some of the changes.

Dr. Palmaz: People ask me why was the Palmaz-Schatz stent so crude, but it was the first. When we designed it, we knew it was crude and were unhappy with it. There were limitations because of the manufacturing technology. Electromechanical discharge machining can cut only straight lines; that's why the original stent was limited to straight features. We wanted curvy features and conceived of more flexible stents. Later lasers came about. You can make any design you want using CAD-CAM techniques. Now there are hundreds of them.

Medscape: Will the drug-eluting stents be around for a while?

Dr. Palmaz: For the time being, the use of drug-eluting stents is going to stay in the coronaries. It seems the way to go and I don't see big changes in the coronary business in the next few years. I suspect that more drug-elusion stents are going to come to market. They'll get optimized, just like the plain stent got optimized. But in the background, plain metal stents have been improving and have had dropping restenosis rates. The issue is price. Plain metal stents cost a third of the drug-eluting stents. If they are better, then the drug-eluting stents won't be as appealing because of their price. For instance, the restenosis rates of the new stents made with L-605 look like they are dropping into the teens. If the late restenosis rates of the drug-eluting stents get up to 10% then the difference will be just a few points.

Medscape: How will this affect when different stents are used?

Dr. Palmaz: I think that, in the future, the use of stents will be stratified. Drug-eluting stents might be used only strictly when they are needed, in patients such as diabetics who have a high risk of restenosis. Others patients will receive regular stents.

Medscape: Are there other new directions for stents?

Dr. Palmaz: Over the next few years we'll see things like ceramic coatings for stents and improved biocompatibility. We're going to see nanoengineering to optimize surfaces for cell adhesion. I think these technologies have the promise of bringing restenosis rates down. Another very exciting area is the use of microelectronics with these devices. Microelectronics is evolving so quickly in other areas of medicine that the application of this to stents is going to be inevitable. There will be a whole revolution in the use of electronics to make interactive stents.

Medscape: What would interactive stents do?

Dr. Palmaz: Microelectronics would let stents transmit information outside the body, about basic physiologic function, or even function of the stent itself. They could be designed to measure flow, pressure, and temperature. They could probably tell you the thickness of a thrombus or the tissue forming on the inside of a stent. Further on, you could create detectors for an amplifier for electrical activity so that you could have electrical activity of the heart or the brain being transmitted out. You could have things like accelerometers placed inside the stent so that you could actually derive force parameters, like stroke forces of the heart transmitted out to give you an idea of heart function.

Medscape: How would these devices work?

Dr. Palmaz: Tied in with this are radiofrequency-powered devices. Devices are being developed for the consumer industry in a massive fashion, and they will cost pennies. The basic principle is that there is a little microscopic device in which you can beam a radiofrequency, and that energy will be converted into electrical energy. It will power its own system and beam back information. I think there's a bright future with all of this. I can see microelectronics being incorporated in devices; it will be inevitable.

Medscape: And what about the role of the radiologist?

Dr. Palmaz: When people ask me what the future of the specialty is, I say that radiologists are playing a central role in all of this. This will cross specialties and will go across systems. Interventional radiology will be putting these radiofrequency-powered devices in for muscle stimulation or in the brain or heart. They're everywhere. The precise locations will be determined by the use of 3D imaging modalities. Radiologists are the only ones who are capable of using that technology.