Vice President Dick Cheney made the problem famous, but thousands of  Americans each year need a new round of treatment to fix a heart problem they thought was already solved.

The setback generally goes something like this: Having experienced a chest pain or heart attack, the patient undergoes a procedure to open up the clogged artery, and to install a tiny mesh-like device called a stent to keep the artery propped open. But in many cases, this foreign object causes the body to react with scar tissue and the artery narrows again.

To combat this re-clogging process - which is called restenosis and affects roughly 30 to 50 percent of patients, like Cheney, who have stents - scientists are aggressively testing a variety of drug-coated stents that would release inflammation-reducing medications. These drug-coated stents, which are available in Europe, are expected to radically alter the treatment of cardiovascular disease.

"The anticipation is extraordinary,'' 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 treament for coronary heart disease is vast." Coated stents will probably be on the US market in the next year or so, with several major companies in various stages of clinical trials.

The leaders are Cordis (a Johnson & Johnson company), Boston Scientific and a joint effort by Guidant Corporation and Cook Inc. Some preliminary data show an almost unheard-of 100 percent success rate (meaning zero restenosis) for the drug-delivery stents after two years of follow up. These results are particularly impressive given that patients who receive regular stents often get a diagnosis of restenosis within a year.

Coated stents are expected to replace substantially coronary artery bypass surgery, an expensive, highly invasive operation now performed on more than 350,000 Americans a year. The bypass surgery will probably still be needed for some heart patients who also have diabetes and for those whose arteries are completely blocked.

But 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," that is, arteries with fatty deposits that have not yet ruptured (a process that can cause an instant heart attack).

Coated stents are nothing less than a "revolution,'' says Dr. James  Muller, director of clinical research in cardiology at Massachusetts General Hospital and co-director of the CIMIT Vulnerable Plaque Program. "They are wonderful."

Dr. Jesse Currier, associate director of the adult cardiac catheterization  lab at the UCLA Medical Center, puts it even more emphatically: "This is Neil Armstrong, one giant leap for interventional cardiology...this is a huge, huge quantum leap."

Commonplace as they now are, regular stents have actually been on the US 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, 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. Some researchers have also tried coating stents with heparin, a blood thinner. But heparin-coated stents have not proved ideal, in part because heparin dissolves instantly in water - or blood - which means that it disappears rapidly from the area where it's needed.

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, " says Edelman.

Indeed, inflammation is now believed to be a root cause of both 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 in atherosclerosis. 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 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.

Working with others at MIT, Edelman began years ago to search for ways to accomplish this slow release. Most drugs, he says, cannot move through sheets of polymer materials. But if the polymer sheet is melted and mixed with a drug, when it's recast, it looks like a sponge with drug-filled channels supported by walls of the polymer materials.

Once implanted in the body, fluid enters the channels and dissolves the drug so that it can then leave the polymer sponge. The more curvy (or "tortuous") the channels, the longer it takes for the drug to be released. A number of teams have worked to adapt the polymer technology to stents.

Yet another hurdle was figuring out which drugs to use. One early choice was an antibiotic called actinomycin-D. But to researchers' surprise, it proved no better than a bare stent at reducing restenosis.

Another was a coating with paclitaxel, the active form of Taxol, a drug used to treat cancers of the breast and other tissues. The drug works by slowing cell proliferation. At moderate doses, says Rogers at Brigham and Women's Hospital, paclitaxel holds "tremendous promise, essentially wiping out restenosis." But at the considerably higher doses used in one early trial, paclitaxel-coated stents triggered clots and heart attacks, Rogers notes.

Still, researchers knew they were fundamentally on the right track and a compelling series of studies recently made public shows just how effective coated stents - using drugs, such as paclitaxel or sirolimus - can be.

Two years ago, a pilot study involving 45 patients in the Netherlands and another 30 in Brazil suggested that the Cordis stent coated with a drug called sirolimus (also known as rapamycin) could help prevent restenosis.

But it was the 2-year follow up on these patients, presented this spring at the meeting of the American College of Cardiology in Atlanta, that blew other scientists away: a restenosis rate of zero.

Another study called RAVEL was also presented at the Atlanta 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 (SIRIUS) at Lenox Hill Hospital in New York City and other centers. The 6-month follow up data are not yet public, but the initial data is being submitted to the US 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. 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 - a kind of stent sandwich.

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 US next year," says Donovan.

The third main contender for bringing a drug-coated stent to the US 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 are expected to square off in court in early June over distribution rights for stents coated with paclitaxel, which is made by a company called Angiotech Pharmaceuticals in Vancouver, Canada.

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.

There will certainly be bumps in the road to developing future generations of coated stents. But to a degree unusual in medical circles, cardiologists believe that even the first coated stents to reach the US market will bring vast improvements to America's heart patients.

Granted, there is still a lot to learn about the use of stents, particularly in people who have already had bypass surgery. "Who knows? " adds Edelman of MIT, "New delivery strategies may bring us to the day when we not only do not need coatings on stents, and we may not need the stents, either."

Judy Foreman is Lecturer on Medicine at Harvard Medical School and an affiliated scholar at the Women's Studies Research Center at Brandeis University. Her column appears every other week. Past columns are available on www.myhealthsense.com

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