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Drug-Eluting Stents - Part II

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Drug Eluting Stent Center
The following is Part II of a two-part article which includes:
(1) An introduction to drug-eluting stents (also known as "drug coated stents", "medicated stents", or "DES");
(2) A history of drug-eluting stents, covering the evolution and mechanisms of these devices.

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


Part II. A History:
Evolution, Development and Outlook for Drug-Eluting Stents

Stent from early 90's
typical coronary stent from the early 90's
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 the balloon was dilated. Although the artery would be opened successfully using a balloon, in 3-5% 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.


cross section of
cross section of restenosed artery

The Dilemma of Restenosis
A second problem soon became evident as well. After balloon angioplasty 30-40% of all coronary arteries began to close up again with excess tissue growth, called restenosis. 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.


Close-up of early
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. Gary Roubin, Cesare Gianturco, Julio Palmaz and Richard Schatz were working on such stents 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 1993, the Gianturco-Roubin Flex-Stent became the first coronary stent approved for use in the United States, followed shortly by the Palmaz-Schatz. 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
Close-up of stent mounted on a balloon, circa 1995
Close-up of stent mounted
on a balloon, circa 1995
Although bare metal stents virtually eliminated many of the complications of abrupt artery closure, restenosis persisted. While the rates of restenosis 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.

A drug-eluting stent, circa 2002
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.


"Stent Wars"
Stent Wars
The status and availability of drug-eluting stents have been the subject of many legal disputes and other issues, which some time ago Angioplasty.Org labeled as "Stent Wars". These devices were initially adopted so quickly that they doubled the world market for stents to $5 billion annually. Although the use of drug-eluting stents fell significantly when concerns over stent thrombosis first surfaced in 2006, the introduction of newer and better second and third generation drug-eluting stents, along with studies showing increased efficacy and safety of these devices, has made DES the primary device used in interventions. Currently in the U.S., the DES market is shared by Medtronic, Abbott and Boston Scientific. Cordis/J&J, manufacturer of the CYPHER, the first FDA-approved DES, was unable produce a successful second generation device and so announced in 2011 that it was ceasing production of the CYPHER and dropping out of the stent market entirely.

These 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.

Video not loaded
Animation depicting how the resorbable device works
courtesy Abbott Vascular

Taking a different approach, Abbott currently sells in Europe (not yet available in the U.S.) a completely bioabsorable stent which will totally disappear after it has done its work. A number of other companies, such as Biosensors, Stentys, etc., also manufacture drug-eluting stents with different drug/polymer/stent combinations, but these also are not yet approved for use in the U.S.

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.

in-depth Read the latest information about drug-eluting stents.

Late 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 DAPT 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
Angioplasty.Org Image
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 available to 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 of possible complications and the cost of repeat procedures is continually being reduced. And diabetics, a patient population that previously has not seen great success with interventional procedures, can now be treated with stents specifically approved for diabetics.

in-depth Get more information and resources for patients and stenting in our PatientCenter.

And so advances the story of interventional cardiology, started 40 years ago on a kitchen table....

 

Return to Part I. Drug-Eluting Stent Basics

 

Revised February 2013, Angioplasty.Org staff