Doctors may reconsider which of their patients should receive drug-coated stents in light of the recommendations by a Food and Drug Administration panel of expert advisers.
Patients with conditions not specifically approved by the FDA for treatment with drug-coated stents make up nearly two-thirds of the cases in which the devices are used. Because of this, the recommendations could affect millions.
Over the course of the two-day meeting, the panel agreed that the use of drug-coated stents is "not detrimental" in approved cases. However, the panel did acknowledge data showing these devices increase the likelihood of clot formation, even in these patients.
In "off-label" patients -- those whose heart conditions fall outside of FDA approval criteria -- the panel expressed concerns that the increase in clot formation could have health risks.
"For those people who got their stents off-label, there was the concern of an increased risk of stent thrombosis leading to death and [heart attack]," says Dr. George Vetrovec, chairman of the division of cardiology at Virginia Commonwealth University and a panel member. "But that increased risk is probably also true of bare metal (nondrug-coated) stents as well."
Vetrovec says the main finding of the panel is that more research is needed to determine the long-term risk of drug-coated stents.
"Time and time again, we came back to the fact that there was not enough data for the answers that people wanted," he says.
Staying on Anti-Clotting Drugs Key
Meanwhile, two studies earlier this week suggested there is an increased risk of heart attack and death when patients with drug-coated stents stop taking anti-clotting medications.
Stents are tiny tubes of metal mesh used to prop open clogged coronary arteries so the heart can receive an adequate blood supply. Manufacturers developed drug-coated varieties of the stents to solve the problem of scar tissue closing the artery back up -- a condition called restenosis.
However, two studies this week in the Journal of the American College of Cardiology and the Journal of the American Medical Association suggest that unless patients who receive drug-eluting stents continue to take Plavix indefinitely, they could more than double the risk of heart attack or death.
At the beginning of the FDA discussions, FDA reviewer Andrew Farb described the increased risk as "small but significant."
Studies presented at the meeting demonstrated a modest increase in clotting problems associated with drug-coated stents. Vetrovec says this finding could mean a change in guidelines for how long patients continue to take anti-clotting medication after having a stent put in.
"There was a lot of talk over the need for [anti-clotting drugs] beyond the three- to six-month period, which is in the current package instructions," he says, adding that patients with drug-coated stents will now likely be advised to take the medicines for at least one year.
Some experts who were present at the meeting say a current lack of definitive data of the long-term effects of drug-coated stents in patients obscures the true threat to patients.
"Clearly, the companies have taken the point of view that if you look at the whole collection of data, everyone is making a big deal over nothing," says Dr. Richard Shemin, professor and chairman of cardiothoracic surgery at Boston Medical Center, who attended the hearings. "And some believe that just staying on the anti-clotting therapy will solve the problem."
Shemin says additional trials should be performed to truly assess the safety of the devices.
Millions worldwide have at least one drug-eluting stent in their bodies, and today most of the 800,000 patients per year who have angioplasty operations receive a drug-eluting stent.
And many of these patients may be alarmed at the news that going off their clot-busting medications could increase their risk of death.
"Patients are scared to death believing that they have a 'time bomb' in their chest," says Dr. Carl J. Pepine, chief of cardiovascular medicine at the University of Florida in Gainesville.
Patients Taking Note
Since receiving two stents in February, Mark Edmonds' quality of life has improved dramatically, the 42-year-old says.
"I feel like a human being again," Edmonds says. "I haven't had any bad side effects so far."
Edmonds, who works for a plumbing and heating supply company in Summit, Ill., is one of the hundreds of thousands of Americans who received DES devices last year.
But now, new research suggests that patients with DES devices must continue to take their anti-clotting medications indefinitely. Doing otherwise could more than double their risk of a heart attack or death.
And since a year's supply of the clot-busting drug Plavix costs roughly $1,400, the findings could saddle patients with a long-term economic burden.
Edmonds says even though his Plavix is partially covered by insurance, he still pays $50 per month in co-pay. With a dozen other drugs to buy to keep his blood pressure in check, he says his monthly medicine bills can add up.
But now he says he can no longer afford to put Plavix at the bottom of his list.
"I wish I would have known about that risk, because I've missed taking my Plavix before for about 2½ to three weeks because I couldn't afford it," Edmonds says. "I wish it would have been explained to me."
Drug-Eluting Still Better than Bare Metal?
Despite the new findings about drug-coated stents, previous research shows that they still give better short-term results than their bare-metal predecessors, which do not have a drug coating.
Jean Redstone, a patient in her 60s who received a bare metal stent in January 1997, says her artery closed back up only weeks after the stent had been put in.
"My doctor told me at the time not to worry about it, but it did turn out my stent was failing," she says. "My next stress test showed that my heart was not getting enough blood. It was very upsetting."
In September 1997, Redstone had to return to the operating room for bypass surgery to open the two coronary arteries that had closed down since the stent had been put in -- the original artery, as well as the one adjacent to it.
"At that time drug-eluting stents were not an option," she says. "I think just shortly after my bypass operation it was all over the news, and I was thinking, 'Now this would have saved me.' But it turns out that may have been wrong also."
Assessing the Risks
Experts say that the research brings to light new considerations when it comes to drug-eluting stents.
"With two separate studies reaching the same conclusion, it is time to take this issue seriously," says Dr. Deepak Bhatt, associate professor of medicine at the department of cardiovascular medicine of the Cleveland Clinic Foundation.
However, some experts are concerned that the medical community is overreacting to a small risk.
"This is a little like 'Chicken Little,' says Dr. William O'Neill, executive dean of clinical affairs at the University of Miami's Miller School of Medicine. "Overall, there is no data to suggest that compared to bare metal stents, there are more deaths or [heart attacks] with DES."
O'Neill says there is a risk -- one out of 200 per year -- of clotting problems related to the stent. But he says this risk should not pose a huge concern for stent patients in general.
"If a stent clots, it does not automatically result in death," O'Neill says. "For these reasons, it is unreasonable to suggest that everyone with a DES be treated for life with Plavix."
Another question that must be considered is whether the early benefits afforded by drug-eluting stents outweigh the slight increase of risk seen in terms of clotting.
"My view is that the overall benefit of DES far outweighs the potential risk of the rare occurrence of late-stent thrombosis," said Shukri David, chief of the Providence Hospital and Medical Centers section of cardiology in Southfield, Mich. "The rate of open heart surgery has decreased by about 20 to 30 percent around the country, largely due to the DES."
Contributing to this argument is the decrease in the need for future surgery seen with drug-coated stents.
"At our institution, the rate of late-stent thrombosis is less than 1 percent in more than 3,000 DES cases," David says.
With this in mind, some experts say the biggest risk associated with the studies will be a potential increase in patient fear over drug-eluting stents.
"There is a great risk that there will be overreaction as the public sees things as all good or as all bad," says Dr. Stuart Seides, associate director for cardiology at the Washington Hospital Center in Washington. "But very few things are all good or all bad in medicine.
"My fear is that someone picks up a newspaper or sees a television show and the takeaway message is that this is bad and we are killing a lot of people by placing the stents. That would be a very damaging and destructive takeaway message if the public looked at it that way."
What Patients Should Do
Experts suggest it may be safest for patients receiving stents to continue taking their Plavix indefinitely.
"It mostly means that it will increase the use of Plavix for an extended period of time -- at least a year on Plavix, and for those who don't have a contraindication, indefinitely," says Rob Califf, vice chancellor for clinical research at Duke University. "However, we need better studies to see when Plavix could be discontinued over the long run."
Califf says the best course of action for patients is to continue taking the drug until their doctor suggests otherwise.
"Basically, if it's a recent stent and they are taking Plavix, recommend staying on it and contacting their doctor to find out how long they need to be on Plavix," he says. "If it is an old stent that they have gotten in the past two years, and it is a patient in whom Plavix has been discontinued, they should contact their doctor and ask them if they should go back on it."
And both Edmonds and Redstone say that given the choice, they would have their stent procedures again.
"If it came down to a choice between that and a heart attack, yes, I'd definitely do the same thing again," says Edmonds.
"I think that if I had known then what I know now, I still would have taken the stent and hoped for the best," Redstone says. "What choice do you have?"