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Drug Eluting Stent Overview


The following article provides an overview of drug-eluting stents (a.k.a "drug coated stents" or "medicated stents" or "DES") which gives a basic understanding of the history and mechanisms of these devices

For more in-depth information and late-breaking articles about drug-eluting stents, visit our Drug-Eluting Stent Center.

 


typical coronary stent
from the early 90's
    A Brief History of Stenting
The concept of the stent grew directly out of interventional cardiologists' experience with angioplasty balloons in the first decade of use (1977-87). Sometimes the wall of the coronary artery became weakened after balloon dilatation. Although the artery would be opened successfully using a balloon, in a small percentage of cases, the artery would collapse after the balloon was deflated -- sometimes this might not happen until the patient had been moved to the recovery room. Since there was no interventional "fix" available, the only option for this patient was emergency bypass graft surgery to repair the problem.

The Dilemma of Restenosis
A second problem soon became evident as well. 30-40% of all coronary arteries began to close up again after balloon angioplasty. By the mid-80's various radiologists and cardiologists were working on solutions to these problems, designing new devices in hopes they would provide more safety and durability to the procedures. Lasers, tiny "shavers", rotational "polishers" -- many tools were miniaturized to be delivered via catheter.

  

cross section of
restenosed artery


Close-up of early
Palmaz-Schatz stent

The First Stents
One such device was the stent -- a metal tube or "scaffold" that was inserted after balloon angioplasty. The stent itself was mounted on a balloon and could be opened once inside the coronary artery. Julio Palmaz and Richard Schatz were working on such a stent in the United States; others in Europe were developing their own designs. In 1986, working in Toulouse, France, Jacques Puel and Ulrich Sigwart inserted the first stent into a human coronary artery. In 1994 the first Palmaz-Schatz stent was approved for use in the United States. Over the next decade, several generations of bare metal stents were developed, with each succeeding one being more flexible and easier to deliver to the narrowing.

A Persistent Problem
But while stents virtually eliminated many of the complications of abrupt artery closure, restenosis persisted. Although the rates were somewhat lower, bare metal stents still experienced reblocking (typically at six-months) in about 20-25% of cases, necessitating a repeat procedure. The interventional cardiology community also learned that restenosis, rather than being a recurrence of coronary artery disease, actually was the body's response to what Andreas Gruentzig called the "controlled injury" of angioplasty and was characterized by growth of smooth muscle cells -- roughly analogous to a scar forming over an injury.
  

Close-up of stent mounted on a balloon, circa 1995


A drug-eluting stent,
circa 2002
  
Development of Coated and Drug-Eluting Stents
More and more, the solution moved away from the purely mechanical devices of the 90's and toward pharmacologic advances that were being made. If interventional medicine, using the body's circulatory system as a "highway" to deliver therapy, worked with devices, it could also work with medicines. Physicians and companies began testing a variety of drugs that were known to interrupt the biological processes that caused restenosis. Stents were coated with these drugs, sometimes imbedded in a thin polymer for time-release, and clinical trials were begun.

Drug-Eluting Stent Basics
Sometimes referred to as a “coated” or “medicated” stent, a drug-eluting stent is a normal metal stent that has been coated with a pharmacologic agent (drug) that is known to interfere with the process of restenosis (reblocking). Restenosis has a number of causes; it is a very complex process and the solution to its prevention is equally complex. However, in the data gathered so far, the drug-eluting stent has been extremely successful in reducing restenosis from the 20-25% range to single digits. There are three major components to a drug-eluting stent:

  • Type of stent that carries the drug coating
  • Method by which the drug is delivered (eluted) by the coating to the arterial wall (polymeric or other)
  • The drug itself – how does it act in the body to prevent restenosis?
  

Artist's rendition of coated stent on balloon in artery

Interventional procedure being performed in the catheterization lab
  
In addition, there are several decisions made by the interventional cardiologist that result in a successful stent placement, whether of the drug-eluting or bare metal variety:
  • Correct sizing of the stent length to match the length of the lesion, or blocked area
  • Correct sizing of the stent diameter to match the thickness of the healthy part of the artery
  • Sufficient deployment of the stent, making sure that the stent, once placed at the optimum site in the blocked artery, is expanded fully to the arterial wall – under-expansion can result in small gaps between the stent and arterial wall which can lead to serious problems such as blood clots, or Sub-Acute Thrombosis (SAT)


Usually the sizing and the assessments of expansion are made by viewing the real-time angiogram in the cath lab, although some cardiologists also are using more detailed information obtained through intravascular ultrasound imaging.

Finally, in addition to aspirin, the patient must take an anti-clotting or antiplatelet drug, such as clopidogrel, prasugrel or ticlopidine (brand names Plavix, Effient or Ticlid) for a year or more after the stenting, to prevent the blood from reacting to the new device by thickening and clogging up the newly expanded artery (thrombosis). Ideally a smooth, thin layer of endothelial cells (the inner lining of the blood vessel) grows over the stent during this period and the device is incorporated into the artery, reducing the tendency for clotting.

 

  

Intravascular ultrasound image of stent in artery
Stent Wars
  
"Stent Wars"
The status and availability of drug-eluting stents have been the subject of many legal disputes and other issue, which some time ago Angioplasty.Org labeled "Stent Wars". These devices were initially adopted so quickly that they doubled the world market for stents to $5 billion annually. While usage of drug-eluting stents was reduced immediately after concerns over stent thrombosis first surfaced in 2006, with further studies showing increased efficacy and the introduction of newer second and third generation drug-eluting stents, DES use is again increasing. Currently in the U.S., the DES market is shared by Abbott, Boston Scientific and Medtronic. Cordis/J&J, manufacturer of the CYPHER, the first FDA-approved DES, was unable produce a second generation device and so announced in 2011 that it was ceasing production of the CYPHER and dropping out of the stent market entirely.

The newer drug-eluting stents have thinner, more flexible struts, thinner and more biocompatible polymers that elute the drug and, in most randomized clinical trials and observational studies, all show increased efficacy and safety: both the risks of stent thrombosis and the rate of restenosis have been reduced from the first generation devices.

Taking a different approach, both Abbott and Germany-based Biotronik are testing a completely bioabsorable stent which will totally disappear after it has done its work. OrbusNeich received CE mark approval in 2005 for its Genous stent which, rather than using drugs to suppress excess tissue growth, utilizes an bio-engineered coating to attract a thin "all-natural" endothelial layer within hours. A number of other companies, such as Biosensors, Stentys, etc, are working on other drug/polymer/stent combinations.

The major positive for drug-eluting stents is that all the approved devices have shown significant reduction of restenosis in clinical trials and in the "real world". DES have also shown dramatic reduction in reinterventions in diabetics as well -- this is a population that has been highly susceptible to restenosis in the past.

Stent Thrombosis
There is some evidence that drug-eluting stents may be susceptible to an event known as "late stent thrombosis", where the blood-clotting inside the stent can occur one or more years post-stent, after the recommended one-year of dual antiplatelet therapy has ended. While this was seen infrequently in the first-generation Taxus and Cypher stents, thrombosis is extremely dangerous, fatal in over one third of cases. To prevent thrombosis, a full course of post-stent antiplatelet therapy is very important and patients should not stop taking aspirin, Plavix, Effient or Ticlid without consulting their interventional cardiologist.

The issue of late stent thrombosis, although discussed within the profession since drug-eluting stents were introduced, received widespread publicity at the September 2006 World Congress of Cardiology meeting in Barcelona when three European studies pointed to higher rates than had previously been seen (see our feature, "Problems Resurface with Drug-Eluting Stents" for detailed coverage). Late stent thrombosis was one of the major issues discussed at the 2006 TCT Meeting and the FDA scheduled a public meeting in early December 2006 on the issue. The conclusion was that more information was needed, especially about the use of devices in off-label settings, but that when used as directed, there did not seem to be greater risks of death or heart attack with drug-eluting stents.

However, within a short time, newer second-generation drug-eluting stents came to market and studies have shown the risk of late stent thrombosis to be even lower. In fact the Swedish Stent Registry (SCAAR) which reported great concerns over stent thrombosis in 2006, has now shown the exact opposite, with drug-eluting stents showing far great safety and effectiveness than bare metal stents.

Developments in this field can be fast and furious. Keep abreast of the constantly changing status of clinical trial results and controversies in our Drug-Eluting Stent NewsCenter.


  
Outlook for Patient Care
While there continue to be questions about the use (or overuse) of drug-eluting stents vs. medical therapy alone, and which is the best stent, the development of these sophisticated devices and the new wave of treatment options are further expanding the tools of cardiologists. The durability of interventional procedures to treat coronary artery disease non-surgically has increased exponentially with the introduction of drug-eluting stents. The specter, possible complications (and expense) of repeat procedures, will be vastly reduced. And diabetics, a patient population that previously has not seen great success with angioplasty and stent procedures, can now be treated with more confidence.

And so advances the story of interventional cardiology, started 30 years ago on a kitchen table....

revised September 2011 by Burt Cohen