Drug-Coated Stents Have A Dark Side

There's a dark side to drug-coated stents.

Drugs in the devices keep arteries from reclogging after balloon angioplasty — a big problem with earlier, bare-metal stents. Introduced just three years ago, drug-coated, or drug-eluting, stents became all the rage among cardiologists.

But in rare cases, they seem to cause sudden cardiac death or severe heart attack a year or more after they're implanted.

Concern heightened with reports at last September's meeting of the World Congress of Cardiology in Barcelona, Spain. Despite reassurances that the risks are small, data presented at an October meeting of heart specialists in Washington, D.C., confirms there is a problem.

"There is a possible dark side to drug-eluting stents," Deepak L. Bhatt, M.D., associate director of The Cleveland Clinic's heart center, tells WebMD. "The risk has been exaggerated — but there is something there. People are not dropping in droves due to drug-eluting stents, but you can't say there is no cause for concern."

"It is a real concern," agrees Richard Milani, M.D., head of preventive cardiology at New Orleans' Ochsner Clinic. "There are more questions than we have answers. We don't know how often this really happens. We don't really know who the people most at risk are," he tells WebMD.

How great is the risk? The data aren't in yet.

But in an analysis of clinical-trial data, Bhatt and colleagues found that over the course of a couple of years, patients who get drug-coated stents have 0.5 percent more risk of dangerous blood clots than those who get bare-metal stents.

"The absolute risk to an individual patient is less than one in 200," Bhatt says. But "with a million stents going in each year in the U.S. and twice that number worldwide, this is not trivial."

2 Steps Forward, 1 Step Back

For a person with a blocked artery, doctors have two basic treatments.

One is bypass surgery — taking a blood vessel from somewhere else in the body and using it to bypass the blockage.

The other solution is to insert a catheter into the artery, inflate a balloon that reopens the blockage, and place a stent (or wire-mesh cylinder) in the blood vessel to hold it open while it heals.

As the artery heals, new cells grow over the inside of the stent, essentially making it part of the blood vessel.

Unfortunately, the body tends to see the stent as a foreign object. Sometimes, scar tissue forms inside the stent, once again blocking the artery.

New drug-eluting stents are coated with a polymer that slowly releases a powerful drug. This drug keeps scar tissue from forming.

Unfortunately, it also slows the healing process. That's a problem — because until the blood vessel heals inside of the stent, there's a risk of deadly blood clots.

The Benefits

Stents have revolutionized the treatment of blocked arteries. They've vastly reduced the need for bypass surgery.

And the new drug-eluting stents have greatly decreased the risk of stent blockage. The newly identified risk does not outweigh the overall benefit of the new stents.

Johnson & Johnson subsidiary Cordis Corp. and Boston Scientific make the two drug-eluting stents that now have FDA approval.

Boston Scientific did not respond to WebMD's interview request.

Cordis spokeswoman Mariela Melendez notes that patients who get bare-metal stents also may rarely suffer sudden cardiac death and heart attacks.

"At the end of the day, we believe this is a rare event," Melendez tells WebMD. "It is a significant challenge that we take very seriously. We want to get to the bottom of this. But at this point, we don't see much difference between bare-metal stents and drug-coated stents."

Most of the blood clots that lead to death or heart attack happen when patients stop taking anticlotting drugs.

Currently, combination treatment with Plavix and aspirin is recommended for all patients for the first year. Patients who can tlerate this treatment even longer may be able to avoid the additional risk.

"In the end, it is a wash with respect to the risk of death or heart attack," Bhatt says. "For the right patient, a drug-eluting stent is the best option. But for the wrong patient, someone that has a bleeding problem or a recurrent gastrointestinal bleeding issue such as diverticulitis, the drug-eluting strategy may not be so great for them. Because keeping them on aspirin and Plavix for a long while would be a bad thing."

Bottom Line for Patients

What does all this mean for the millions of people with drug-coated stents in their bodies? Medical journalist Miriam Shuchman, M.D., reviewed the stent issue for the Nov. 9 issue of The New England Journal of Medicine.

"It is true the risk for any given patient is small — but patients need to talk with their doctors," Shuchman tells WebMD.

"They will be hearing they need to stay on their Plavix and aspirin for longer than they initially thought," he says.

"Where this does not lead is to a situation where patients must say, 'Take it out.' The level of risk is not such that you would do that," Shuchman says. "I did not hear any doctor say that was indicated."

Bhatt says doctors and patients may have been a bit too enthusiastic about drug-coated stents. They are not, he says, the last word in treating blocked arteries.

"Thinking that drug-eluting stents are for every patient and for all lesions is wrong. The use of drug-eluting stents got ahead of the science," he says. "But I would not hesitate to put in drug-eluting stents merely because of the recent attention this issue has received."

What does the FDA say?

It's calling for a "more formal evaluation." That may come as soon as December, when the FDA has scheduled a meeting of device manufacturers, researchers, and heart experts.

New Stents on the Way

Tomorrow's drug-coated stents may solve the blood-clotting problem.

One strategy is to make the drug-carrying polymer dissolve when its job is done. Another strategy is to make stents that dissolve entirely. One company working on this problem is Biosensors International.

"With any new advance in science, there is always a 'Gotcha!' and it appears there is a very small risk of late blood-clotting with some of the first-generation stent designs," Biosensors Chief Technology Officer John Shulze tells WebMD. "We believe we have a solution for that."

Biosensors has developed a drug-eluting polymer stent coating that dissolves over time. Shulze says small clinical trials show it works. But he warns that larger studies will be needed.

"These products are coming. And for doctors, I think they couldn't come soon enough," Shulze says.

Another idea is to speed the process by which the body coats stents with a new lining of blood vessel cells. Once this lining is in place, there's little risk of blood clots.

In the Nov. 7 issue of the Journal of the American College of Cardiology, Mayo Clinic researchers Gurpreet S. Sandhu, M.D., Ph.D., and colleagues report that a magnetized stent can speed this process.

From the blood, Sandhu's team isolates cells that grow into blood vessel linings.

They then grow these cells in a Petri dish along with tiny iron particles. As the cells grow, they incorporate these particles.

Then, during an angioplasty procedure, the researchers insert a magnetized stent and release the iron-carrying cells upstream of the stent. The magnetized stent holds the cells in place, where they quickly grow into a new blood-vessel lining.

It works — but so far, only in large animals. Human trials await the development of safer materials.

"Human studies are several years down the road," Sandhu tells WebMD. "We want to make sure this is 100 percent safe before we try this in patients."

Bhatt asks patients to remember that every technology comes with risks as well as benfits.

"Having said that, the current generation of drug-eluting stents is an advance," he says.

"Next generations will be better. Each one of these technologies will have certain limitations and liabilities," says Bhatt. "Every intervention does carry some risk. We just need to make sure the procedure really is indicated in the first place."

SOURCES: Shuchman, M. The New England Journal of Medicine, Nov. 9, 2006; vol 355: pp 1949-1952. Pislaru, S. Journal of the American College of Cardiology, Nov. 7, 2006; vol 48: pp 1839-1845. News release, FDA. Cordis Corp. News release, Cordis Corp. News release, Boston Scientific. Boston Scientific web site. News release, Biosensors International. News release, Mayo Clinic. Miriam Shuchman, M.D., State University of New York, Buffalo. Deepak L. Bhatt, M.D., associate director, The Cleveland Clinic Cardiovascular Coordinating Center, Ohio. Mariela Melendez, spokeswoman, cardiology division, Cordis Corp., Miami Lakes, Fla. Richard Milani, M.D., section head, preventive cardiology, Ochsner Clinic Foundation, New Orleans. Gurpreet S. Sandhu, M.D., Ph.D., Mayo Clinic, Rochester, Minn. John Shulze, chief technology officer, Biosensors International.