Coated Stents Smooth Cardiology Care Recovery
If you are rushed to an American hospital today with chest pain caused by clogged arteries to your heart, the chances are good that you will get an artery-opening procedure called angioplasty, and the insertion of a tiny, mesh-like device called a stent to keep your arteries open.
If you had the same symptoms in Europe, you’d still get angioplasty, but with an important twist. Instead of a regular stent, you and your physician could opt for a new coated stent that, in addition to keeping arteries open through sheer structural support, releases drugs that combat the inflammatory process that can cause uncoated stents to fill up with scar tissue.
Coated stents will probably be on the U.S. market in the next year or so. And no matter which company gets there first--the leaders are Cordis (a Johnson & Johnson company), Boston Scientific and a joint effort by Guidant Corp. and Cook Inc.--the new stents are likely to revolutionize the way doctors treat heart patients.
Most important, they are expected to reduce dramatically the current 30% to 50% rate at which arteries re-narrow after stenting, a process called restenosis. In fact, some data show an almost unheard-of 100% success rate (meaning zero restenosis) for the drug-delivery stents after two years of follow-up.
“The anticipation is extraordinary in this field,” said Dr. Campbell Rogers, director of the cardiac catheterization laboratory at Brigham and Women’s Hospital. “The impact of having a new, less-invasive and more effective treatment for coronary artery disease is vast.”
The new stents will likely become the preferred option not just for the 1 million or so Americans a year who now get regular stents, but for hundreds of thousands of others currently deemed ineligible because they have too many bad arteries. They may also be used for hundreds of thousands of others with “vulnerable plaques,” arteries with fatty deposits that have not yet ruptured.
“If the results of these early trials are confirmed in larger studies, coated stents should significantly reduce the need for coronary artery bypass surgery,” says Dr. Sidney C. Smith, chief science officer for the American Heart Assn. and a professor of medicine at the University of North Carolina at Chapel Hill.
Dr. Jesse Currier, associate director of the adult cardiac catheterization lab at UCLA Medical Center, put it even more emphatically: “This is Neil Armstrong, one giant leap for interventional cardiology ... this is a huge, huge quantum leap.”
In fact, the biggest downside may turn out to be that financially strapped hospitals could suffer as patients choose the new stents over bypass surgery, a huge money-earner.
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Commonplace as they now are, regular stents have actually been on the U.S. market for only a few years, after two major trials showed that simply placing an uncoated stent into an artery was better than angioplasty alone in reducing the risk of restenosis. (In angioplasty, doctors thread a tube called a catheter up through an artery in the groin to the coronary arteries, then push a button to inflate a balloon to compress the plaque against the artery wall.)
Even though uncoated stents do just fine at keeping artery walls from collapsing, their sheer presence can create new problems, notes Dr. Elazer Edelman, director of the Harvard-MIT Biomedical Engineering Center, a professor of health sciences and technology at MIT and a cardiologist at Brigham and Women’s Hospital. The worst possibility is that, immediately after insertion, the stent can trigger blood clots, a process that doctors guard against by giving patients anti-clotting drugs such as aspirin and Plavix. But there’s another danger, too, after insertion of a stent. “You’re leaving a foreign body behind. Now, as opposed to a single injury from inflating a balloon, you have a rigid, metal object that can trigger a slow, chronic inflammatory process,” Edelman says. Indeed, inflammation is now believed to be a root cause of atherosclerosis, the initial formation of plaques, and of restenosis, the re-clogging of arteries during the healing process after angioplasty and stent insertion. Cholesterol, specifically LDL (the “bad” cholesterol) is still a major culprit. But its effects include stimulation of the body’s natural inflammatory response to injury--sending immune cells to clean up the area.
To fight this inflammatory process in people with regular stents, doctors have tried local application of radiation, including radioactive stents and radioactive pellets placed temporarily within the stent. This approach has not been shown to prevent restenosis--and may actually impair normal healing of the artery--but can help combat restenosis that has already occurred. A potentially better solution, Edelman and other researchers reasoned, might be to coat stents with drugs that could stop proliferation of inflammatory cells. One idea was to coat a stent directly with a medication, the approach taken by Guidant/Cook. Another was to create polymers (chains of identical chemicals) that could act as a glue to hold drugs on and inside a stent in such a way as to release the drugs slowly, over a matter of days or even weeks.
A series of studies recently made public shows just how effective coated stents can be.
Two years ago, a pilot study involving 45 patients in the Netherlands and 30 in Brazil suggested that the Cordis stent coated with a drug called sirolimus (also known as rapamycin) could help prevent restenosis.
The studies were led by Dr. Patrick Serruys at the Thorax Center in Rotterdam and Dr. Jose Eduardo Sousa at the Dante Pazzanese Institute of Cardiology in Sao Paulo, Brazil. The two-year follow-up on these patients, presented this spring at the meeting of the American College of Cardiology in Atlanta, showed a restenosis rate of zero.
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Another study called RAVEL, led by Dr. Marie-Claude Morice, head of Interventional Cardiology at the Institut Hospitalier Jacque Cartier in Massy, France, was also presented at the Atlanta cardiology meeting. Like the pilot study, the stents in this research were coated with sirolimus, and the results on 238 patients in Europe and Latin America were “astonishing,” says Currier of UCLA. Several hundred patients were followed for up to one year “with no major adverse cardiac events, no restenosis.”
Currently, the sirolimus-coated stent is being tracked in an even bigger study of 1,100 patients (called SIRIUS) at Lenox Hill Hospital in New York City and other centers. The six-month follow-up data are not yet public, but a spokesman for Johnson & Johnson, David Swearingen, says the initial data is being submitted to the Food and Drug Administration for approval of this stent product. The sirolimus-coated stent, called Cypher, has already received regulatory approval for marketing in Europe.
The other main approach is coating stents with paclitaxel, but not in the high doses that proved dangerous. Boston Scientific Corp., based in Natick, uses a polymer to stick paclitaxel onto its stent. In the pilot study of 61 patients, researchers found zero restenosis after six months of follow-up. A larger study of about 500 patients “provided further support for the safety of paclitaxel,” says company spokesman Paul Donovan. The paclitaxel stent also seems to prevent restenosis, a third study shows, as a stent placed inside a stent already in the artery.
Boston Scientific’s most important study, TAXUS IV, which involves more than 1,000 patients at 80 medical centers, is still underway, but the company is optimistic: “We plan to launch a drug-coated stent in Europe this year and in the U.S. next year,” Donovan says.
The third main contender for bringing a drug-coated stent to the U.S. market is Guidant/Cook. Like Boston Scientific, Guidant/Cook uses paclitaxel to coat its stents. But therein lies a problem. Boston Scientific and Guidant/Cook squared off in court last week over distribution rights for stents coated with paclitaxel, which is made by a company called Angiotech Pharmaceuticals in Vancouver, Canada. Although a federal court ruled in favor of Boston Scientific, Guidant/Cook has vowed to appeal. Guidant is currently conducting a trial of its paclitaxel stent in more than 1,000 patients in a study called DELIVER, which is now in its follow-up phase. To a degree unusual in medical circles, cardiologists believe that even the first coated stents to reach the U.S. market will bring vast improvements to America’s heart patients. “Who knows?” says Edelman of MIT. “New delivery strategies may bring us to the day when we not only do not need coatings on stents, we may not need the stents, either.”
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Judy Foreman is a lecturer on medicine at Harvard Medical School. She can be reached at judyforeman@attbi.com. He column appears occasionally.
