FDA: Stent patients face blood clot riskDec 5, 2006 | AP
Patients implanted with drug-coated stents to hold open their choked arteries face a small but significant risk of blood clots, health officials said Tuesday. A new study recommended they take clot-busting medications indefinitely.
Growing concern about the long-term safety of drug-coated stents comes to a head this week when the Food and Drug Administration convenes a two-day meeting to discuss clotting risks associated with the devices.
In documents released Tuesday, the FDA said it is unknown whether there is an increased risk of death or heart attack in patients fitted with the so-called drug-eluting stents. However, those patients do face an increased risk of blood clots a year or more after surgery compared with people fitted with bare-metal stents, the agency said in citing recent studies.
About 6 million people worldwide have one or more drug-eluting stents in their bodies.
The FDA is seeking advice on a wide range of questions on the stents, including whether to update the labels with new warnings, identify patients for whom they aren't appropriate and perhaps change federal recommendations on how long people should take blood thinners like Plavix and aspirin following stent surgery.
Plavix, also known as clopidogrel, can cost $1,400 a year.
The agency also wants advice on what research is needed, both on the drug-coated stents already on the market and others it has yet to consider approving.
"The single most important thing is to be able to provide the American public with the best current state of our knowledge with respect again to the risk and benefits associated with these products," FDA devices chief Dr. Daniel Schultz told reporters.
The miniature lattice-shaped tubes are coated with drugs that slowly dissolve or elute into the bloodstream to prevent regrowth of tissue that can clog arteries anew. Boston Scientific Corp. and Johnson & Johnson are the only two companies approved to sell the drug-coated versions.
Labels on those stents recommend patients take baby aspirin and Plavix for either three or six months, depending on the manufacturer, following surgery. Many patients remain on the drugs longer.
Multiple studies have suggested the risk of blood clots, heart attack and death rises in patients who stop taking those drugs early. The FDA staff said it is unknown how long patients should remain on the drugs to prevent life-threatening clots from forming.
In the new study, researchers found that patients who quit taking Plavix even six or 12 months after receiving a drug-coated stent faced more than twice the risk of premature heart attack or death as did patients who remained on the drug.
"The bottom line from our paper, for doctors and patients, is these results tilt the balance to the fact you should stay on clopidogrel if you have a drug-eluting stent indefinitely until further data tell us how long you should be on it," said Dr. Robert Califf, a Duke University cardiologist.
He estimates that 20 percent to 30 percent of people who have stents take Plavix for 12 months or more. That potentially puts tens of thousands worldwide at risk of heart attack or death each year, he said.
Details appeared Tuesday on the Web site of the Journal of the American Medical Association.
Califf and his colleagues also recommend a 10,000-patient, three-year study to determine whether long-term Plavix use is beneficial. One researcher questioned whether that would be useful, given rapid advances in stent technology and the time required to complete such a study.
"You're talking four to five years down the road and all these stents are going to be obsolete," said Dr. Spencer King, a cardiologist at the Fuqua Heart Center in Atlanta's Piedmont Hospital and past president of the American College of Cardiology.
Another suggested enrolling patients could be difficult if not downright unethical, since researchers would stop giving Plavix to some patients after a year or two and presumably switch them to placebo or dummy pills. Others would stay on the real drug for three years.
"I don't know many cardiologists or their patients who would want to be on the placebo end of that," said Dr. Robert Bonow of Northwestern University and a past president of the American Heart Association.
Boston Scientific has acknowledged a slight increase in clotting associated with its drug-coated stent, the Taxus, but said it's seen no corresponding increase in heart attacks or deaths. Johnson & Johnson said there's no significant difference in clotting, heart attack or death rates between its stent, the Cypher, and bare metal versions. Both companies said use of the drug-coated stents reduces the need for follow-up surgeries to reopen clogged arteries.
However, multiple studies have suggested the risk of blood clots, heart attack and death rises in drug-coated stent patients who stop taking Plavix and aspirin early.
Long-term risks of treatment with Plavix are unknown, the FDA cautioned. The drug, also known as clopidogrel, can cause major bleeding.
The FDA said the risk of blood clotting applies to the drug-coated stents when used as labeled. However, the agency acknowledges that more than 60 percent of the stents probably are implanted in types of patients not studied during the trials of the devices that led to their approval. That off-label use often involves more complex cases; those patients may well benefit more from the drugs in the coated stents but also face greater clotting risk, complicating the issue.
Doctors now implant stents in about 650,000 Americans a year. Since the first drug-coated stents gained FDA approval in 2003, they have gone on to capture 80 percent of the stent market. Doctors like them because there is less reclogging of the arteries in patients given drug-eluting stents.
Another significant question is whether that early benefit is outweighed by a later increased risk of clotting, heart experts said. Why that would be the case is unknown, although researchers have suggested a connection with the rate at which cells in the arteries grow back to envelop the stents. They're also looking at the polymers used to bind the drugs.
Meanwhile, Bonow and others suggested drug-eluting stents should be used more selectively and judiciously. In part that could depend on assessing the risk that a patient's arteries could clog again after surgery or how well they could tolerate or afford long-term use of Plavix.