More than 60 patients who received a popular new drug-coated heart stent have died, the government disclosed Wednesday a surprising increase since the last health warning about the device just months ago.
The Cypher stent is a tiny metal scaffold used in patients with heart disease. It props open a cleaned-out artery and, unlike other stents, emits a drug to reduce the chances the artery will clog again.
But that drug doesn't prevent a different risk posed by all stents: blood clots that form around the device and can cause a heart attack.
Cypher stents became available in April, and in July the Food and Drug Administration warned that it had received reports of those blood clots in 34 Cypher recipients, including five who died.
Wednesday, the FDA issued a second warning: It has counted more than 290 reports of blood clots in Cypher recipients, and in more than 60 the device was associated with the patient's death. Those clots occurred up to 30 days after the stent was implanted.
In addition, the FDA has received more than 50 reports of allergic-type reactions: pain, hives, fever and problems with breathing and blood pressure. The FDA said some of those people died, although it did not reveal how many.
The cause of the problems hasn't been determined, the FDA said, stressing that it doesn't know whether the Cypher is riskier than a bare-metal stent. In studies that led to the Cypher's approval, it proved no more likely to cause blood clots than competing stents.
About 260,000 Cypher stents have been distributed to U.S. hospitals and 180,000 abroad, making the number of problems reported very small in comparison. And some of the increased reporting since July is likely because of increased publicity, cautioned FDA device evaluation chief Dan Schultz.
However, the FDA often learns of only a fraction of the side effects that occur with medical products. So, in a public health warning to doctors posted on its Web site, the FDA urged doctors to promptly report problems with Cypher recipients.
"We have a signal," Schultz said. "It's a strong enough signal that as a responsible public health organization we need to at least inform people" while scientists determine if there's really a serious risk.
Cypher maker Cordis Corp., a Johnson & Johnson subsidiary, is conducting a 2,000-patient study that, among other things, will track rare side effects. Enrollment is nearing completion, and data on blood clots should be available by the end of January, Cordis said.
"There's no perfect treatment," said Dr. Richard Nesto, cardiovascular medicine chief at the Lahey Clinic in Burlington, Mass., and a spokesman for the American Heart Association.
Still, "this does merit scrutiny," he added, saying cardiologists are watching the Cypher saga closely and probably will remind patients of the importance of taking their anticlotting medication.
Cypher recipients must take anticlotting drugs for three months after getting the stent, not the mere two weeks prescribed for bare-metal stents.
In addition, the FDA wants doctors to be sure they choose the right size stents and implant them properly.
Cordis' analysis of the side-effect reports suggests blood clots are no more common with the Cypher than with bare-metal stents, said spokesman Martin Schildhouse.
Questions about blood clots haven't hurt Cypher usage: Today, about 60 percent of all stents implanted are Cyphers, up from about 45 percent in July, Schildhouse said.
Tuesday, December 12, 2006
Hospitals revert to older stent models as FDA investigates new ones
With a new report blaming drug-coated heart stents for a fivefold increase in the risk of clotting problems and a Food and Drug Administration panel poised to investigate the devices, hospitals that once embraced the new stents are starting to retreat to an older, cheaper version.
Drug-coated stents are implanted in more than a million Americans a year to keep arteries propped open. They are the next-generation of a metal mesh device inserted after angioplasty, a procedure where doctors use a balloon-tipped catheter to open pathways to the heart.
Arteries treated with the first bare metal stents had the tendency to close in some patients. The drug coating was designed to inhibit the development of scar tissue and stop the vessel from clogging again.
The promise of the new device was so impressed upon the medical community that doctors turned to the drug-coated version for most patients since they came on the market in 2003. Some hospitals used drug-coated stents in more than 90 percent of their patients.
But recent reports of clotting issues are causing doctors to think twice about using the newer models in some patients. A new report released last week, based on research led by the Cleveland Clinic, showed a four- to fivefold increased risk of clots compared to the bare metal variety.
Some hospitals have responded by cutting their use of drug-coated stents by 10 percent or more since reports of potential risks began surfacing last fall about so-called “late stent” clotting which develops after the device has been in patients for several months or longer.
“There is that nagging concern about late-stent thrombosis that (clotting) concern is out there,” said Dr. Gary Schaer, director of the cardiac catheterization lab at Rush University Medical Center in Chicago.
At Rush, Schaer said the hospital routinely had been placing drug-coated stents in patients about 85 percent of the time, but recently that number has dropped to about 75 percent.
In its most recent two-month period, Rush said 68 percent of angioplasty patients received drug-coated stents. During the same period last year, 88 percent received the drug-coated variety. The hospital said it places about 600 coronary stents in patients annually.
Those types of numbers are bad news for stent manufacturers, including North Chicago-based Abbott Laboratories, which placed a huge bet on heart stents when it purchased Guidant Corp.’s cardiovascular business earlier this year for more than $4 billion. Abbott currently has a drug-coated stent in development for U.S. patients.
Currently, only two drug-coated stents are on the U.S. market: Boston Scientific Corp.’s Taxus, and Johnson & Johnson’s Cypher and both are losing sales. Although Abbott has a drug-coated stent in some European countries, analysts say J&J and Boston Scientific dominate a $6 billion worldwide market.
Drug-coated stents are big business. They can cost $2,200 or more, compared to $600 to $800 for the uncoated variety, hospitals say.
But the companies and some doctors maintain the risks are small, saying there have not been enough studies completed to warrant a return to bare metal stents. Even hospitals that have curtailed implanting the drug-coated version say they will stick with it for most patients.
At Loyola University Medical Center in west suburban Maywood, where the hospital implants more than 1,500 stents in more than 1,300 patients a year, doctors there say the risk is not enough to justify a retreat from drug-coated stents.
“There is no evidence that bare metal stents are any safer they were not as well scrutinized as drug eluting stents,” said Dr. Fred Leya, director of interventional cardiology at Loyola University Health System, parent of the medical center. While Leya said the risk of clotting in patients, or so-called “late-stent thrombosis” worrisome, he said clotting after the stent has been in the artery for several months or even longer than a year is “no more than 3 to 4 percent,” of patients. A widely reported study last month found a 2.9 percent risk of clotting after three years and the potential to rise.
Leya said the benefits of drug-coated stents outweigh risks, which include re-clogging of the arteries or having to re-implant bare metal stents as well as risks from angioplasty procedure itself.
The U.S. Food and Drug Administration has convened a special panel for this week to look at the clotting issue. The meeting is a regularly scheduled meeting to discuss heart devices, but the clotting issue of stents has prompted the FDA to call additional outside experts in to be a part of the discussion.
The FDA has not yet disclosed the list but leading experts in cardiology, drug and device safety are expected. The panel could recommend labeling changes to drug-coated stents. The FDA usually follows recommendations of its panels.
For its part, Abbott believes newer drug-coated stents like the Xience model it hopes to have on the U.S. market by 2008, could be safer.
An Abbott-funded study earlier this year showed Xience had a “thrombosis” rate of 0.5 percent at six months usage compared with 1.3 percent rate for Boston Scientific’s Taxus.
Abbott and doctors say all stents are different and should not be lumped in the same bucket when searching for a cause to the clotting issue. Stents have different drug coatings and are im
Until Abbott’s drug-coated stent hits, the market, analysts say the company could benefit in a return to bare metal stents, which it sells as part of its purchase from Guidant. “We have seen a small uptick in bare metal stents in the last few months,” said Morrison.
Leya said drug-coated stents reduced the tendency for arteries to re-clog to just 5 to 10 percent of patients, compared to 20 to 25 percent for the bare metal variety. By comparison, 30 to 50 percent of patients who simply had an angioplasty procedure eventually had their arteries re-clog, he said.
Although no one is certain about what causes the clotting issues, cardiologists think some of it may be due to patients not taking their medications to reduce the risk of clots.
The pills can cost $3 to $4 a day if they do not have drug coverage.
Drug-coated stents are implanted in more than a million Americans a year to keep arteries propped open. They are the next-generation of a metal mesh device inserted after angioplasty, a procedure where doctors use a balloon-tipped catheter to open pathways to the heart.
Arteries treated with the first bare metal stents had the tendency to close in some patients. The drug coating was designed to inhibit the development of scar tissue and stop the vessel from clogging again.
The promise of the new device was so impressed upon the medical community that doctors turned to the drug-coated version for most patients since they came on the market in 2003. Some hospitals used drug-coated stents in more than 90 percent of their patients.
But recent reports of clotting issues are causing doctors to think twice about using the newer models in some patients. A new report released last week, based on research led by the Cleveland Clinic, showed a four- to fivefold increased risk of clots compared to the bare metal variety.
Some hospitals have responded by cutting their use of drug-coated stents by 10 percent or more since reports of potential risks began surfacing last fall about so-called “late stent” clotting which develops after the device has been in patients for several months or longer.
“There is that nagging concern about late-stent thrombosis that (clotting) concern is out there,” said Dr. Gary Schaer, director of the cardiac catheterization lab at Rush University Medical Center in Chicago.
At Rush, Schaer said the hospital routinely had been placing drug-coated stents in patients about 85 percent of the time, but recently that number has dropped to about 75 percent.
In its most recent two-month period, Rush said 68 percent of angioplasty patients received drug-coated stents. During the same period last year, 88 percent received the drug-coated variety. The hospital said it places about 600 coronary stents in patients annually.
Those types of numbers are bad news for stent manufacturers, including North Chicago-based Abbott Laboratories, which placed a huge bet on heart stents when it purchased Guidant Corp.’s cardiovascular business earlier this year for more than $4 billion. Abbott currently has a drug-coated stent in development for U.S. patients.
Currently, only two drug-coated stents are on the U.S. market: Boston Scientific Corp.’s Taxus, and Johnson & Johnson’s Cypher and both are losing sales. Although Abbott has a drug-coated stent in some European countries, analysts say J&J and Boston Scientific dominate a $6 billion worldwide market.
Drug-coated stents are big business. They can cost $2,200 or more, compared to $600 to $800 for the uncoated variety, hospitals say.
But the companies and some doctors maintain the risks are small, saying there have not been enough studies completed to warrant a return to bare metal stents. Even hospitals that have curtailed implanting the drug-coated version say they will stick with it for most patients.
At Loyola University Medical Center in west suburban Maywood, where the hospital implants more than 1,500 stents in more than 1,300 patients a year, doctors there say the risk is not enough to justify a retreat from drug-coated stents.
“There is no evidence that bare metal stents are any safer they were not as well scrutinized as drug eluting stents,” said Dr. Fred Leya, director of interventional cardiology at Loyola University Health System, parent of the medical center. While Leya said the risk of clotting in patients, or so-called “late-stent thrombosis” worrisome, he said clotting after the stent has been in the artery for several months or even longer than a year is “no more than 3 to 4 percent,” of patients. A widely reported study last month found a 2.9 percent risk of clotting after three years and the potential to rise.
Leya said the benefits of drug-coated stents outweigh risks, which include re-clogging of the arteries or having to re-implant bare metal stents as well as risks from angioplasty procedure itself.
The U.S. Food and Drug Administration has convened a special panel for this week to look at the clotting issue. The meeting is a regularly scheduled meeting to discuss heart devices, but the clotting issue of stents has prompted the FDA to call additional outside experts in to be a part of the discussion.
The FDA has not yet disclosed the list but leading experts in cardiology, drug and device safety are expected. The panel could recommend labeling changes to drug-coated stents. The FDA usually follows recommendations of its panels.
For its part, Abbott believes newer drug-coated stents like the Xience model it hopes to have on the U.S. market by 2008, could be safer.
An Abbott-funded study earlier this year showed Xience had a “thrombosis” rate of 0.5 percent at six months usage compared with 1.3 percent rate for Boston Scientific’s Taxus.
Abbott and doctors say all stents are different and should not be lumped in the same bucket when searching for a cause to the clotting issue. Stents have different drug coatings and are im
Until Abbott’s drug-coated stent hits, the market, analysts say the company could benefit in a return to bare metal stents, which it sells as part of its purchase from Guidant. “We have seen a small uptick in bare metal stents in the last few months,” said Morrison.
Leya said drug-coated stents reduced the tendency for arteries to re-clog to just 5 to 10 percent of patients, compared to 20 to 25 percent for the bare metal variety. By comparison, 30 to 50 percent of patients who simply had an angioplasty procedure eventually had their arteries re-clog, he said.
Although no one is certain about what causes the clotting issues, cardiologists think some of it may be due to patients not taking their medications to reduce the risk of clots.
The pills can cost $3 to $4 a day if they do not have drug coverage.
Sunday, December 10, 2006
Heart Stents Reconsidered by Medical Community
For the better part of the last decade, heart stents have been celebrated as one of the most important developments in the medical field, and, with sales of heart stents reaching $6 billion annually, it’s also been one of the fastest-growing segments of the industry. Yet, it seems with each passing day that more and more questions arise regarding their long-term safety.
Recent evidence points to an increased risk of fatal blood clotting associated with a particular type of stent, the drug-coated stent. Drug-coated stents were virtually non-existent as recently as five years ago, but now they command more than 85 percent of the stent market. The FDA has scheduled meetings for this coming December in order to discuss the issue in more detail and perhaps call for further studies.
This week, an FDA official urged Boston Scientific and Johnson & Johnson, the two largest stent producers, to conduct further research into the matter. “The real question is how to expand the knowledge base for many thousands of patients being treated ‘off-label,’” said Bram Zuckerman, director of the FDA’s division for cardiac devices.
The debate over the use of stents has divided the medical community. Most agree that the use of stents–mesh tubes used to hold open clogged arteries–have been instrumental in saving thousands of lives. Beyond that, other questions remain: Are too many doctors recommending the stenting process rather than more traditional treatments such as medication or surgery? Are the more expensive drug-coated stents more dangerous than cheaper non-coated ones? Are the safety risks connected to the method and accuracy of implantation, rather than the product itself?
Several studies this year have pointed to long-term risks of clotting associated with the drug-coated stents in particular. The coated stents are used to prevent tissue from reforming in the arteries. What seems most alarming about them, according to recent studies, is that the risk of clotting has not diminished over time, forcing some patients to remain on anti-clotting medication for extended periods.
Last week, a New England Journal of Medicine study reported that the risk of stroke or death was more than two times higher for patients receiving stents than it was for patients who are treated by endarterectomy (an invasive surgical treatment). That study specifically regarded patients suffering from carotid artery blockage. In a commentary in the same issue of the NEJM, Dr. Anthony J. Furlan said, “The benefits of surgery in reducing the long-term risk of stroke need to be weighed against the immediate risk of death or stroke as a complication of the surgery.” He also said that, based on current FDA guidelines, stenting should be reserved for those patients with a significant (more than 70 percent) blockage who have displayed stroke symptoms and are at a high risk of surgical complications.
Recent evidence points to an increased risk of fatal blood clotting associated with a particular type of stent, the drug-coated stent. Drug-coated stents were virtually non-existent as recently as five years ago, but now they command more than 85 percent of the stent market. The FDA has scheduled meetings for this coming December in order to discuss the issue in more detail and perhaps call for further studies.
This week, an FDA official urged Boston Scientific and Johnson & Johnson, the two largest stent producers, to conduct further research into the matter. “The real question is how to expand the knowledge base for many thousands of patients being treated ‘off-label,’” said Bram Zuckerman, director of the FDA’s division for cardiac devices.
The debate over the use of stents has divided the medical community. Most agree that the use of stents–mesh tubes used to hold open clogged arteries–have been instrumental in saving thousands of lives. Beyond that, other questions remain: Are too many doctors recommending the stenting process rather than more traditional treatments such as medication or surgery? Are the more expensive drug-coated stents more dangerous than cheaper non-coated ones? Are the safety risks connected to the method and accuracy of implantation, rather than the product itself?
Several studies this year have pointed to long-term risks of clotting associated with the drug-coated stents in particular. The coated stents are used to prevent tissue from reforming in the arteries. What seems most alarming about them, according to recent studies, is that the risk of clotting has not diminished over time, forcing some patients to remain on anti-clotting medication for extended periods.
Last week, a New England Journal of Medicine study reported that the risk of stroke or death was more than two times higher for patients receiving stents than it was for patients who are treated by endarterectomy (an invasive surgical treatment). That study specifically regarded patients suffering from carotid artery blockage. In a commentary in the same issue of the NEJM, Dr. Anthony J. Furlan said, “The benefits of surgery in reducing the long-term risk of stroke need to be weighed against the immediate risk of death or stroke as a complication of the surgery.” He also said that, based on current FDA guidelines, stenting should be reserved for those patients with a significant (more than 70 percent) blockage who have displayed stroke symptoms and are at a high risk of surgical complications.
Controversy Swirls Around FDA Meeting on Drug Coated Stents
A planned FDA safety review regarding the use of drug-coated stents is facing intense scrutiny after it was revealed that six doctors on the advisory panel have financial links to stent makers Johnson & Johnson and Boston Scientific. The meeting, set for Thursday and Friday of this week, has been scheduled in order to discuss significant risks of blood clotting associated with the use of drug-coated stents. The FDA granted conflict-of-interest waivers to all six of the physicians in question.
In advance of the meeting, the FDA released documents today related to an FDA staff review that noted that the drug-coated stents “are associated with a small but significant risk of late-stent thrombosis.” Stents are wire-mesh devices used to unclog arteries. The drug-coated stents are intended to prevent scar tissue from forming in the arteries, but preliminary research has determined that the coated stents may increase the probability of adverse events, including heart attacks and strokes.
Agency critics are amazed and appalled that the FDA would allow panel members with significant ties to the companies whose devices are being reviewed. In a statement last month, Merrill Goozner of the Center for Science in the Public Interest said, “The scientists who advise the FDA should be free of all financial ties to firms whose products are under review. The public’s faith in the integrity of the process will be undermined by any reform legislation that allows physicians and scientists with conflicts of interest to continue serving on these committees.”
In response to the latest controversy, Goozner told the Newark Star-Ledger: “There are literally thousands of experts all over this country who are well-schooled in the details of this field. But instead of reaching out to that community to get a totally unbiased look at this question, the FDA appointed a committee on which a substantial fraction have conflicts of interest directly with manufacturers of products being evaluated. It’s almost impossible to have confidence in the outcomes of this kind of deliberation.”
According to Bloomberg News, one member of the advisory panel is Robert Harrington, who runs a Duke University research institute funded by both J&J and Boston Scientific.
Drug-coated stents have been used in 4 million patients and have sales in the $6 billion range annually. They are significantly more expensive than bare stents, but apparently they are more dangerous as well.
In advance of the meeting, the FDA released documents today related to an FDA staff review that noted that the drug-coated stents “are associated with a small but significant risk of late-stent thrombosis.” Stents are wire-mesh devices used to unclog arteries. The drug-coated stents are intended to prevent scar tissue from forming in the arteries, but preliminary research has determined that the coated stents may increase the probability of adverse events, including heart attacks and strokes.
Agency critics are amazed and appalled that the FDA would allow panel members with significant ties to the companies whose devices are being reviewed. In a statement last month, Merrill Goozner of the Center for Science in the Public Interest said, “The scientists who advise the FDA should be free of all financial ties to firms whose products are under review. The public’s faith in the integrity of the process will be undermined by any reform legislation that allows physicians and scientists with conflicts of interest to continue serving on these committees.”
In response to the latest controversy, Goozner told the Newark Star-Ledger: “There are literally thousands of experts all over this country who are well-schooled in the details of this field. But instead of reaching out to that community to get a totally unbiased look at this question, the FDA appointed a committee on which a substantial fraction have conflicts of interest directly with manufacturers of products being evaluated. It’s almost impossible to have confidence in the outcomes of this kind of deliberation.”
According to Bloomberg News, one member of the advisory panel is Robert Harrington, who runs a Duke University research institute funded by both J&J and Boston Scientific.
Drug-coated stents have been used in 4 million patients and have sales in the $6 billion range annually. They are significantly more expensive than bare stents, but apparently they are more dangerous as well.
Saturday, December 9, 2006
Analysis: Panel urges warning on stents
A Food and Drug Administration advisory panel recommended new warnings Friday for popular medical devices used in millions of patients with cardiovascular disease.
Experts said the two brands of drug-coated stents available in the U.S. should carry new warnings that the devices may increase the risk of sudden heart attack or death in many patients.
Stents are mesh tubes used to hold arteries open after physicians clear away blockages, usually with an inflatable balloon angioplasty. Approximately one million Americans receive stent implants each year.
The devices are made either of bare metal mesh or a newer, coated metal that steadily releases a drug into artery walls to prevent formation of scar tissue. Two drug-coated stents, Taxus, made by Boston Scientific and Cypher, made by Cordis, a division of Johnson & Johnson have exploded in popularity since they came on the market in 2003 and 2004.
Stents are credited with providing a non-surgical alternative to heart bypass operations for many patients with artery disease. But new data released earlier this year suggested that drug-coated versions may increase the risk of heart attacks and sudden deaths by as much as 0.5 percent per year, starting a year after implantation.
The data and resulting press coverage prompted FDA to organize a hastily-convened two-day expert panel to decide how the agency should react. Friday's conclusions came one day after the panel informally voted that the benefits of drug-coated stents outweigh the risks for average patients.
Studies leading to the approval of Taxus and Cypher tested the devices in patients with single, smaller artery blockages. But doctors quickly started using them in patients with blockages in multiple vessels and in those with larger blockages or co-existing diseases like diabetes.
Today, more than six in ten of all drug-coated stent implants are done "off-label," or used beyond their approved indication, according to FDA.
Experts said Friday that the devices' label inserts should now carry a warning that use in more complicated patients increases the risk of dangerous blood clots, heart attack and sudden death.
"If (doctors) use the device in an off-label manner they're not going to get the results that they see in the label," said William Maisel, a cardiologist at Beth Israel Deaconess Medical Center in Boston and chair of the advisory panel.
Experts also said physicians should be urged to extend the use of the blood-thinning drug Plavix in patients who receive drug-coated stents off-label. Current recommendations advise patients to take Plavix along with aspirin for three to six months after implantation, although experts said that should be extended to one year.
The recommendations was not made by a formal vote but were the consensus of panel members. FDA does not have to follow advisory panels' advice, but usually does.
FDA officials said they would move to communicate the recommendations to the public, although the method of that communication is yet to be decided. The agency could choose to add warnings to drug-coated stent labeling, communicate directly with physicians about the risks, or do both.
At the end of the day what I heard loud and clear is that we need to do better job..,communicating to patients and communicating to doctors the best and the latest information," said Dan Schultz, MD, director of FDA's Center for Devices and Radiologic Health. "This meeting needed to happen," he said.
News of the potential for increased risk sparked anxious press reports and worry among many U.S. patients. Experts stressed Friday that there was little need for patients using drug-coated stents to have them removed. Suspected clots and heart attacks blamed on the stents are still thought to be relatively rare. Patients who take blood-thinning drugs according to physician recommendations reduce their risk.
Some experts described the two days of FDA meetings as a kind of reality check on the use of drug-coated stents by U.S. doctors.
"I think we've got to come back to Earth here," said Steven Nissen, chair of cardiovascular medicine at the Cleveland Clinic Foundation and one of the FDA advisors.
There was dissent among panel members. Some worried the issuing new warnings would further frighten patients and physicians away from using stents.
"I haven't seen anything today that's going to change my practice on Mon morning when I go back," said Christopher J. White, chairman of cardiology at the Ochsner Clinic Foundation in New Orleans, and a member of the FDA panel.
In an interview, Ralph G. Brindis, MD, a stent researcher at Kaiser Permanente of Northern California, predicted that the FDA hearings would lead physicians to "more conservatism" in their use of drug-coated stents. He said doctors may now be less likely to use the devices in diabetic patients with multiple blockages or diabetes, instead opting for traditional bypass surgery.
"I think doctors will get the message that rather than using multiple drug-eluting stents, that they'll be a modest swing back to that procedure," said Brindis, who is also chief medical officer of the American College of Cardiology.
Mark Turco, MD, a researcher at Washington Adventist Hospital in Washington, DC, said that drug-dispensing stents were greeted by "unbridled enthusiasm" that outpaced scientific proof for many patients. He said recent news of increased risks then swung public perception to one of near panic over the dangers.
"Hopefully we will soon move to a realistic application where the data will far outweigh the perceptions," he said.
Experts said the two brands of drug-coated stents available in the U.S. should carry new warnings that the devices may increase the risk of sudden heart attack or death in many patients.
Stents are mesh tubes used to hold arteries open after physicians clear away blockages, usually with an inflatable balloon angioplasty. Approximately one million Americans receive stent implants each year.
The devices are made either of bare metal mesh or a newer, coated metal that steadily releases a drug into artery walls to prevent formation of scar tissue. Two drug-coated stents, Taxus, made by Boston Scientific and Cypher, made by Cordis, a division of Johnson & Johnson have exploded in popularity since they came on the market in 2003 and 2004.
Stents are credited with providing a non-surgical alternative to heart bypass operations for many patients with artery disease. But new data released earlier this year suggested that drug-coated versions may increase the risk of heart attacks and sudden deaths by as much as 0.5 percent per year, starting a year after implantation.
The data and resulting press coverage prompted FDA to organize a hastily-convened two-day expert panel to decide how the agency should react. Friday's conclusions came one day after the panel informally voted that the benefits of drug-coated stents outweigh the risks for average patients.
Studies leading to the approval of Taxus and Cypher tested the devices in patients with single, smaller artery blockages. But doctors quickly started using them in patients with blockages in multiple vessels and in those with larger blockages or co-existing diseases like diabetes.
Today, more than six in ten of all drug-coated stent implants are done "off-label," or used beyond their approved indication, according to FDA.
Experts said Friday that the devices' label inserts should now carry a warning that use in more complicated patients increases the risk of dangerous blood clots, heart attack and sudden death.
"If (doctors) use the device in an off-label manner they're not going to get the results that they see in the label," said William Maisel, a cardiologist at Beth Israel Deaconess Medical Center in Boston and chair of the advisory panel.
Experts also said physicians should be urged to extend the use of the blood-thinning drug Plavix in patients who receive drug-coated stents off-label. Current recommendations advise patients to take Plavix along with aspirin for three to six months after implantation, although experts said that should be extended to one year.
The recommendations was not made by a formal vote but were the consensus of panel members. FDA does not have to follow advisory panels' advice, but usually does.
FDA officials said they would move to communicate the recommendations to the public, although the method of that communication is yet to be decided. The agency could choose to add warnings to drug-coated stent labeling, communicate directly with physicians about the risks, or do both.
At the end of the day what I heard loud and clear is that we need to do better job..,communicating to patients and communicating to doctors the best and the latest information," said Dan Schultz, MD, director of FDA's Center for Devices and Radiologic Health. "This meeting needed to happen," he said.
News of the potential for increased risk sparked anxious press reports and worry among many U.S. patients. Experts stressed Friday that there was little need for patients using drug-coated stents to have them removed. Suspected clots and heart attacks blamed on the stents are still thought to be relatively rare. Patients who take blood-thinning drugs according to physician recommendations reduce their risk.
Some experts described the two days of FDA meetings as a kind of reality check on the use of drug-coated stents by U.S. doctors.
"I think we've got to come back to Earth here," said Steven Nissen, chair of cardiovascular medicine at the Cleveland Clinic Foundation and one of the FDA advisors.
There was dissent among panel members. Some worried the issuing new warnings would further frighten patients and physicians away from using stents.
"I haven't seen anything today that's going to change my practice on Mon morning when I go back," said Christopher J. White, chairman of cardiology at the Ochsner Clinic Foundation in New Orleans, and a member of the FDA panel.
In an interview, Ralph G. Brindis, MD, a stent researcher at Kaiser Permanente of Northern California, predicted that the FDA hearings would lead physicians to "more conservatism" in their use of drug-coated stents. He said doctors may now be less likely to use the devices in diabetic patients with multiple blockages or diabetes, instead opting for traditional bypass surgery.
"I think doctors will get the message that rather than using multiple drug-eluting stents, that they'll be a modest swing back to that procedure," said Brindis, who is also chief medical officer of the American College of Cardiology.
Mark Turco, MD, a researcher at Washington Adventist Hospital in Washington, DC, said that drug-dispensing stents were greeted by "unbridled enthusiasm" that outpaced scientific proof for many patients. He said recent news of increased risks then swung public perception to one of near panic over the dangers.
"Hopefully we will soon move to a realistic application where the data will far outweigh the perceptions," he said.
FDA Panel Seeks Warning That Stents May Be Unsafe
New drug-oozing stents widely used to prop open clogged arteries are associated with an increased risk of blood clots, heart attacks and death for the majority of patients receiving the devices, an expert panel concluded yesterday.
Based on the finding, the special 21-member Food and Drug Administration panel recommended that the agency issue new warnings to doctors and patients that the devices' safety has not been established except for relatively low-risk patients, for whom the stents were originally tested and approved.
"If you use the device outside that indication, you're going to have a higher incidence of complications," said William H. Maisel of the Beth Israel Deaconess Medical Center in Boston, who chaired the panel.
The panel stressed that the tiny metal-lattice struts, known as drug-eluting stents, offer advantages over older bare-metal versions for some patients, with the benefits outweighing the risks for the relatively healthy patients for whom the devices have been tested.
It remains unclear whether the devices are causing the complications in other patients; the side effects could be occurring because these patients tend to be sicker. But panel members concluded that until that question can be answered, doctors and patients should be alerted about the potential risks. Several members said they hoped that would make doctors more cautious about using the devices.
"Let's be more judicious about this. Let's be less indiscriminate," said Eric J. Topol of the Scripps Clinic in San Diego.
The panel also recommended that patients who have the stents take anti-clotting drugs for at least a year.
More than 6 million people worldwide have gotten the drug-coated devices, including perhaps 3 million in the United States. At least 800,000 new patients get them each year, making the stents the most common device used to treat heart disease and one of the most common medical procedures of any kind. The panel's recommendations apply to at least 60 percent of those patients.
The FDA is not bound to follow the recommendations, but an official said the agency would respond rapidly.
"There may be things that can be done relatively quickly," the FDA's Daniel G. Schultz said, noting that the warning could take the form of changes in the devices' labels and letters to doctors and patients.
The recommendations came on the second day of a sometimes contentious two-day meeting the FDA urgently convened to determine whether the risks of the devices outweigh the benefits.
The panel concluded that although the devices, compared with older bare-metal versions, may increase the risk of blood clots, drug-eluting stents do not appear to increase the overall risk of heart attacks and strokes when used in the kind of patients for whom they were originally intended. But a majority of patients get them "off-label," or not as intended, and tend to be sicker and have more-complicated conditions, such as diabetes, multiple blockages and blockages in narrower arteries.
In a packed hotel room in Gaithersburg yesterday, the panel listened to presentations from researchers from California, Illinois, North Carolina, Rhode Island, Washington and elsewhere who analyzed the latest data from large registries of patients who had received the stents since they were introduced three years ago. Although the results were mixed, several analyses found an increased risk of blood clots, deaths and heart attacks.
"Do we have evidence that the safety-efficacy balance might be different in the off-label? I think we've heard enough to suggest that that's the case," said Steven Nissen of the Cleveland Clinic.
More than 1 million U.S. heart patients undergo procedures every year to have blocked arteries opened with tiny balloons, after which stents are implanted to keep the vessels open. Scar tissue often grows around the stents, however, narrowing the arteries again and requiring patients to undergo the procedure repeatedly or to have bypass surgery.
The newer stents are coated with a polymer impregnated with drugs that are released slowly, inhibiting scar-tissue growth. Because the devices were shown to be highly effective, they were hailed as a major advance and quickly replaced bare-metal versions for most patients, though the newer stents were tested on and approved for only low-risk patients.
The FDA called for the meeting after studies looking at patients outside tightly controlled clinical trials indicated that a year or more after implantation, patients with drug-coated stents faced increased risks compared with those with bare-metal models. Some researchers have estimated the newer devices might be causing thousands of heart attacks and deaths a year.
Some researchers, along with Boston Scientific Corp. and Johnson & Johnson, which make the two drug-eluting stents sold domestically, say any risks from the devices are offset by the reduced need for repeated procedures and bypass surgery, which carry their own risks.
Patients who get the stents had been advised to take aspirin and the drug Plavix for three to six months to reduce the risk of blood clots. Recent studies have indicated that patients may need to take the drugs longer, perhaps indefinitely. But Plavix is expensive and increases the risk of serious bleeding.
Based on the finding, the special 21-member Food and Drug Administration panel recommended that the agency issue new warnings to doctors and patients that the devices' safety has not been established except for relatively low-risk patients, for whom the stents were originally tested and approved.
"If you use the device outside that indication, you're going to have a higher incidence of complications," said William H. Maisel of the Beth Israel Deaconess Medical Center in Boston, who chaired the panel.
The panel stressed that the tiny metal-lattice struts, known as drug-eluting stents, offer advantages over older bare-metal versions for some patients, with the benefits outweighing the risks for the relatively healthy patients for whom the devices have been tested.
It remains unclear whether the devices are causing the complications in other patients; the side effects could be occurring because these patients tend to be sicker. But panel members concluded that until that question can be answered, doctors and patients should be alerted about the potential risks. Several members said they hoped that would make doctors more cautious about using the devices.
"Let's be more judicious about this. Let's be less indiscriminate," said Eric J. Topol of the Scripps Clinic in San Diego.
The panel also recommended that patients who have the stents take anti-clotting drugs for at least a year.
More than 6 million people worldwide have gotten the drug-coated devices, including perhaps 3 million in the United States. At least 800,000 new patients get them each year, making the stents the most common device used to treat heart disease and one of the most common medical procedures of any kind. The panel's recommendations apply to at least 60 percent of those patients.
The FDA is not bound to follow the recommendations, but an official said the agency would respond rapidly.
"There may be things that can be done relatively quickly," the FDA's Daniel G. Schultz said, noting that the warning could take the form of changes in the devices' labels and letters to doctors and patients.
The recommendations came on the second day of a sometimes contentious two-day meeting the FDA urgently convened to determine whether the risks of the devices outweigh the benefits.
The panel concluded that although the devices, compared with older bare-metal versions, may increase the risk of blood clots, drug-eluting stents do not appear to increase the overall risk of heart attacks and strokes when used in the kind of patients for whom they were originally intended. But a majority of patients get them "off-label," or not as intended, and tend to be sicker and have more-complicated conditions, such as diabetes, multiple blockages and blockages in narrower arteries.
In a packed hotel room in Gaithersburg yesterday, the panel listened to presentations from researchers from California, Illinois, North Carolina, Rhode Island, Washington and elsewhere who analyzed the latest data from large registries of patients who had received the stents since they were introduced three years ago. Although the results were mixed, several analyses found an increased risk of blood clots, deaths and heart attacks.
"Do we have evidence that the safety-efficacy balance might be different in the off-label? I think we've heard enough to suggest that that's the case," said Steven Nissen of the Cleveland Clinic.
More than 1 million U.S. heart patients undergo procedures every year to have blocked arteries opened with tiny balloons, after which stents are implanted to keep the vessels open. Scar tissue often grows around the stents, however, narrowing the arteries again and requiring patients to undergo the procedure repeatedly or to have bypass surgery.
The newer stents are coated with a polymer impregnated with drugs that are released slowly, inhibiting scar-tissue growth. Because the devices were shown to be highly effective, they were hailed as a major advance and quickly replaced bare-metal versions for most patients, though the newer stents were tested on and approved for only low-risk patients.
The FDA called for the meeting after studies looking at patients outside tightly controlled clinical trials indicated that a year or more after implantation, patients with drug-coated stents faced increased risks compared with those with bare-metal models. Some researchers have estimated the newer devices might be causing thousands of heart attacks and deaths a year.
Some researchers, along with Boston Scientific Corp. and Johnson & Johnson, which make the two drug-eluting stents sold domestically, say any risks from the devices are offset by the reduced need for repeated procedures and bypass surgery, which carry their own risks.
Patients who get the stents had been advised to take aspirin and the drug Plavix for three to six months to reduce the risk of blood clots. Recent studies have indicated that patients may need to take the drugs longer, perhaps indefinitely. But Plavix is expensive and increases the risk of serious bleeding.
Panel weighs in on stents
A divided Food and Drug Administration advisory panel Friday said cardiac patients should be warned they face a higher rate of life-threatening complications from unapproved use of drug-coated stents.
The panel said product labels for the stents should be revised to caution doctors and patients that off-label use carries an increased risk of blood clots, heart attack or death.
The devices, which are used to keep arteries open after blockages have been cleared, were approved in 2003 for use in patients with just one clogged vessel. But the stents are widely used off-label in sicker patients with multiple blockages or complicating illnesses, such as diabetes.
In the U.S., unapproved uses of the stents, made by Johnson & Johnson and Boston Scientific Corp., account for about 60% of sales.
These "patients should be warned they should not expect the same outcome" as healthier patients, said panel chairman Dr. William H. Maisel of Beth Israel Deaconess Medical Center in Boston.
The FDA called the panel meeting after a series of studies found the tiny mesh stents increased the risk of complications months and years after they were implanted. Several studies found the devices carried small but significant risk of heart attack or death.
The devices, known as drug-eluting stents, release drugs that prevent blockages caused by a buildup of scar tissue — a complication of bare-metal stents. But the drugs slow healing inside the artery, and that can lead to the formation of clots.
About 3 million people in the U.S. have the drug-coated stents, which generated worldwide sales of more than $5 billion last year.
The panel decided that the devices were safe and effective for the narrow group of patients for whom the devices were approved.
But panel member Dr. Norman S. Kato of Cardiac Care Medical Group in Encino said there is a shortage of conclusive medical research on the safety of the stents in other patients. He said off-label use of the stents could not be justified. He said the increased risk of death "makes me very, very nervous."
Panelist Dr. Eric Topol of Scripps Clinic in San Diego called for "more judicious" use of stents.
Despite the concerns, the panel of 21 experts said there is not enough evidence to restrict use of the stents.
Dr. Christopher J. White of Ochsner Clinic in New Orleans and a member of the advisory panel said it was not surprising to see an increase in complications in sicker patients. He noted that sicker patients who have bare-metal stents also have a higher rate of complications.
"Nothing I heard today is going to change what I do," White said.
The panel recommended those patients who use the stents for unapproved conditions should receive anti-clotting medicine for one year after their procedure. Currently, patients take the anti-clotting drug Plavix for three to six months.
Because the drug is expensive and can cause severe bleeding, the panel said, patients who cannot take the drug for 12 months should not receive coated stents.
The FDA isn't required to follow the panel's advice, but it typically does.
The panel said product labels for the stents should be revised to caution doctors and patients that off-label use carries an increased risk of blood clots, heart attack or death.
The devices, which are used to keep arteries open after blockages have been cleared, were approved in 2003 for use in patients with just one clogged vessel. But the stents are widely used off-label in sicker patients with multiple blockages or complicating illnesses, such as diabetes.
In the U.S., unapproved uses of the stents, made by Johnson & Johnson and Boston Scientific Corp., account for about 60% of sales.
These "patients should be warned they should not expect the same outcome" as healthier patients, said panel chairman Dr. William H. Maisel of Beth Israel Deaconess Medical Center in Boston.
The FDA called the panel meeting after a series of studies found the tiny mesh stents increased the risk of complications months and years after they were implanted. Several studies found the devices carried small but significant risk of heart attack or death.
The devices, known as drug-eluting stents, release drugs that prevent blockages caused by a buildup of scar tissue — a complication of bare-metal stents. But the drugs slow healing inside the artery, and that can lead to the formation of clots.
About 3 million people in the U.S. have the drug-coated stents, which generated worldwide sales of more than $5 billion last year.
The panel decided that the devices were safe and effective for the narrow group of patients for whom the devices were approved.
But panel member Dr. Norman S. Kato of Cardiac Care Medical Group in Encino said there is a shortage of conclusive medical research on the safety of the stents in other patients. He said off-label use of the stents could not be justified. He said the increased risk of death "makes me very, very nervous."
Panelist Dr. Eric Topol of Scripps Clinic in San Diego called for "more judicious" use of stents.
Despite the concerns, the panel of 21 experts said there is not enough evidence to restrict use of the stents.
Dr. Christopher J. White of Ochsner Clinic in New Orleans and a member of the advisory panel said it was not surprising to see an increase in complications in sicker patients. He noted that sicker patients who have bare-metal stents also have a higher rate of complications.
"Nothing I heard today is going to change what I do," White said.
The panel recommended those patients who use the stents for unapproved conditions should receive anti-clotting medicine for one year after their procedure. Currently, patients take the anti-clotting drug Plavix for three to six months.
Because the drug is expensive and can cause severe bleeding, the panel said, patients who cannot take the drug for 12 months should not receive coated stents.
The FDA isn't required to follow the panel's advice, but it typically does.
Thursday, December 7, 2006
Feds questions experts on drug-coated stents
Federal health officials asked experts Thursday whether the drug-coated stents used to prop open the arteries of about 3 million people in the U.S. pose a heightened risk of death or raise other safety concerns that require action.
The two manufacturers of the widely used devices say their benefits outweigh their risks, but the Food and Drug Administration believes patients could face a small but significant chance of blood clots.
The companies, Boston Scientific Corp. and Johnson & Johnson, were in the hot seat as the FDA began two days of meetings to discuss with a panel of outside experts the clotting risks associated with the devices.
Some researchers believe that clotting leads to an increased risk of heart attack and death in patients fitted with the devices - a danger the FDA said is unknown. The agency does believe the clotting risk is real, however.
"Are you certain of that conclusion?" asked panel member Dr. John Somberg, of Rush University Medical Center in Lake Bluff, Ill.
FDA medical officer Dr. Andrew Farb said yes, after acknowledging the difficulty of acting on that information.
"When we have rare events in relatively small numbers, to come up with sweeping conclusions can raise issues," Farb said.
The FDA asked panelists to assess the risk and then provide the agency with their recommendations, including whether to update the labels with new warnings or change guidelines on how long people should take anti-clotting drugs such as Plavix and aspirin following stent surgery.
"It is important to note FDA does not regulate the practice of medicine. However, FDA is responsible for any use of a device that raises a public health concern," FDA medical officer Dr. Takahiro Uchida told the panel.
Boston Scientific acknowledges a slight increase in clotting associated with its drug-coated stent, the Taxus. The company said it has seen no corresponding increase in heart attacks or deaths.
Johnson & Johnson said there is 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 when compared to bare-metal stents. That accounts for the widespread use of the drug-coated versions since their introduction in 2003. Today, more than 60 percent of the stents probably are implanted in higher-risk and other patients not studied before the devices gained FDA approval.
Multiple studies have suggested the risk of blood clots, heart attack and death rises in patients who stop taking Plavix earlier than now recommended. Some doctors recommend patients stay on it indefinitely until more is learned.
But FDA staff said it is unknown how long patients should take the drug, distributed by Bristol-Myers Squibb Co. and Sanofi-Aventis SA.
The FDA also seeks recommendations for research on the drug-coated stents on the market or pending approval. Both Medtronic Inc. and Abbott Laboratories hope to enter the more than $5 billion U.S. market for the drug-coated stents.
The two manufacturers of the widely used devices say their benefits outweigh their risks, but the Food and Drug Administration believes patients could face a small but significant chance of blood clots.
The companies, Boston Scientific Corp. and Johnson & Johnson, were in the hot seat as the FDA began two days of meetings to discuss with a panel of outside experts the clotting risks associated with the devices.
Some researchers believe that clotting leads to an increased risk of heart attack and death in patients fitted with the devices - a danger the FDA said is unknown. The agency does believe the clotting risk is real, however.
"Are you certain of that conclusion?" asked panel member Dr. John Somberg, of Rush University Medical Center in Lake Bluff, Ill.
FDA medical officer Dr. Andrew Farb said yes, after acknowledging the difficulty of acting on that information.
"When we have rare events in relatively small numbers, to come up with sweeping conclusions can raise issues," Farb said.
The FDA asked panelists to assess the risk and then provide the agency with their recommendations, including whether to update the labels with new warnings or change guidelines on how long people should take anti-clotting drugs such as Plavix and aspirin following stent surgery.
"It is important to note FDA does not regulate the practice of medicine. However, FDA is responsible for any use of a device that raises a public health concern," FDA medical officer Dr. Takahiro Uchida told the panel.
Boston Scientific acknowledges a slight increase in clotting associated with its drug-coated stent, the Taxus. The company said it has seen no corresponding increase in heart attacks or deaths.
Johnson & Johnson said there is 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 when compared to bare-metal stents. That accounts for the widespread use of the drug-coated versions since their introduction in 2003. Today, more than 60 percent of the stents probably are implanted in higher-risk and other patients not studied before the devices gained FDA approval.
Multiple studies have suggested the risk of blood clots, heart attack and death rises in patients who stop taking Plavix earlier than now recommended. Some doctors recommend patients stay on it indefinitely until more is learned.
But FDA staff said it is unknown how long patients should take the drug, distributed by Bristol-Myers Squibb Co. and Sanofi-Aventis SA.
The FDA also seeks recommendations for research on the drug-coated stents on the market or pending approval. Both Medtronic Inc. and Abbott Laboratories hope to enter the more than $5 billion U.S. market for the drug-coated stents.
FDA Explores Safety of Heart Stents
New drug-releasing stents used widely to keep clogged heart arteries open appear to increase the risk for potentially life-threatening blood clots more than older bare-metal versions, government investigators told an expert panel assessing the safety of the devices today.
But the blood clot risk from the tiny metal mesh struts, known as drug-eluting stents, appears relatively low and it remains unclear whether it translates into an excess risk for heart attacks or deaths, according to the Food and Drug Administration analysts.
Nevertheless, because some studies have suggested the increased risk of blood clots, known as thrombosis, may be causing thousands of excess heart attacks and deaths each year, it is urgent that experts determine whether their use should be restricted and patients who already have them should be treated longer with anti-clotting drugs, the agency officials said.
"Since stent thrombosis is associated with high rates of death and [heart attacks], continued efforts to clarify the mechanisms of stent thrombosis and interventions to reduce the risk of its occurrence will have public health benefits," the FDA's Andrew Farb said.
The presentations opened a two-day meeting of a special 21-member panel the FDA urgently convened to evaluate the stents, which have quickly become the most commonly used devices for treating clogged arteries. The panel will address a long list of questions, including whether the risks of the devices outweigh their benefits. The FDA is not bound to adopt the panel's recommendations, but the agency usually does.
Hundreds of people packed a large meeting room in Gaithersburg, Md., just outside Washington, for the highly anticipated meeting, including representatives from Johnson & Johnson and Boston Scientific Corp., which make the two drug-eluting stents sold in the United States. Other medical device makers, heart specialists, reporters and patient advocates also attended the meeting.
The safety of the devices has garnered unusually intense attention because the number of people getting drug-coated stents has risen dramatically since they were introduced in 2003. Worldwide, an estimated 6 million people have them, including as many as 3 million in the United States. About 800,000 Americans are getting the stents each year. Worldwide sales are estimated at close to $6 billion.
More than 1 million heart patients each year undergo procedures to open blocked arteries with tiny balloons and then to install stents--hollow lattice tubes--to keep the passageways open. But scar tissue often grows around the stents, narrowing the arteries again and requiring patients to undergo the procedure repeatedly or to have bypass surgery.
The new generation of stents are coated with a polymer impregnated with drugs that filter out slowly, inhibiting the growth of scar tissue. Because the devices were shown to be highly effective they were hailed as a major advance, and most patients now get them.
But scientists began to become concerned that the slowed healing around the devices may prolong the risk of blood clots, which can also block arteries, causing heart attacks and death. Alarm intensified in recent months as studies began reporting that a year or more after implantation, patients with the drug-coated stents face a small but meaningful increased risk of clots, compared with those given bare-metal models, and possibly were experiencing a greater rates of heart attacks and deaths. The excess risk appears to be small, but could translate into thousands of heart attacks and deaths because of the large number of patients receiving the devices.
Patients who get the stents are advised to take aspirin and an anti-clotting drug known as Plavix for at least three to six months to reduce the risk. But recent new studies have also indicated that may not be long enough and they may need to continue taking the drugs, perhaps indefinitely. Plavix, however, is expensive and increases the risk of potentially serious bleeding problems.
The FDA summarized the existing data, concluding that the evidence indicates the devices do carry an increased risk for blood clots. But the agency's experts noted that the studies' design and size were not sufficient to reach any firm conclusions about whether that was translating into increased heart attacks and deaths. It also remained unclear whether extending Plavix use would be effective, the experts said.
The panel members began quizzing the FDA scientists about the findings, including whether the methods for identifying clots and assessing the risk were reliable.
"We think there is a small but significant increased risk in late-stent thrombosis," Farb said.
Boston Scientific and Johnson & Johnson, which have defended the safety of the devices, planned to present their analyses later in the day.
But the blood clot risk from the tiny metal mesh struts, known as drug-eluting stents, appears relatively low and it remains unclear whether it translates into an excess risk for heart attacks or deaths, according to the Food and Drug Administration analysts.
Nevertheless, because some studies have suggested the increased risk of blood clots, known as thrombosis, may be causing thousands of excess heart attacks and deaths each year, it is urgent that experts determine whether their use should be restricted and patients who already have them should be treated longer with anti-clotting drugs, the agency officials said.
"Since stent thrombosis is associated with high rates of death and [heart attacks], continued efforts to clarify the mechanisms of stent thrombosis and interventions to reduce the risk of its occurrence will have public health benefits," the FDA's Andrew Farb said.
The presentations opened a two-day meeting of a special 21-member panel the FDA urgently convened to evaluate the stents, which have quickly become the most commonly used devices for treating clogged arteries. The panel will address a long list of questions, including whether the risks of the devices outweigh their benefits. The FDA is not bound to adopt the panel's recommendations, but the agency usually does.
Hundreds of people packed a large meeting room in Gaithersburg, Md., just outside Washington, for the highly anticipated meeting, including representatives from Johnson & Johnson and Boston Scientific Corp., which make the two drug-eluting stents sold in the United States. Other medical device makers, heart specialists, reporters and patient advocates also attended the meeting.
The safety of the devices has garnered unusually intense attention because the number of people getting drug-coated stents has risen dramatically since they were introduced in 2003. Worldwide, an estimated 6 million people have them, including as many as 3 million in the United States. About 800,000 Americans are getting the stents each year. Worldwide sales are estimated at close to $6 billion.
More than 1 million heart patients each year undergo procedures to open blocked arteries with tiny balloons and then to install stents--hollow lattice tubes--to keep the passageways open. But scar tissue often grows around the stents, narrowing the arteries again and requiring patients to undergo the procedure repeatedly or to have bypass surgery.
The new generation of stents are coated with a polymer impregnated with drugs that filter out slowly, inhibiting the growth of scar tissue. Because the devices were shown to be highly effective they were hailed as a major advance, and most patients now get them.
But scientists began to become concerned that the slowed healing around the devices may prolong the risk of blood clots, which can also block arteries, causing heart attacks and death. Alarm intensified in recent months as studies began reporting that a year or more after implantation, patients with the drug-coated stents face a small but meaningful increased risk of clots, compared with those given bare-metal models, and possibly were experiencing a greater rates of heart attacks and deaths. The excess risk appears to be small, but could translate into thousands of heart attacks and deaths because of the large number of patients receiving the devices.
Patients who get the stents are advised to take aspirin and an anti-clotting drug known as Plavix for at least three to six months to reduce the risk. But recent new studies have also indicated that may not be long enough and they may need to continue taking the drugs, perhaps indefinitely. Plavix, however, is expensive and increases the risk of potentially serious bleeding problems.
The FDA summarized the existing data, concluding that the evidence indicates the devices do carry an increased risk for blood clots. But the agency's experts noted that the studies' design and size were not sufficient to reach any firm conclusions about whether that was translating into increased heart attacks and deaths. It also remained unclear whether extending Plavix use would be effective, the experts said.
The panel members began quizzing the FDA scientists about the findings, including whether the methods for identifying clots and assessing the risk were reliable.
"We think there is a small but significant increased risk in late-stent thrombosis," Farb said.
Boston Scientific and Johnson & Johnson, which have defended the safety of the devices, planned to present their analyses later in the day.
Stents' Day in the Sun
A Food and Drug Administration panel is slated to review safety data on the use of Johnson & Johnson (JNJ) and Boston Scientific's (BSX) drug-eluting stents amid concerns that the devices could lead to greater instances of blood clots.
Specialists on the FDA circulatory system devices panel will meet Thursday and Friday to review safety data, conduct public hearings and determine whether the stent makers will be required to submit additional safety data on their devices.
Some stents, which are used to prop open arteries cleared of plaque, are coated with drugs designed to prevent regrowth of tissue in the area where the device is implanted. But recent studies have found that the polymers that enable the slow release of drugs remain after all active ingredients are absorbed. Scientists worry they could cause a reaction by the immune system, leading to tissue regrowth within the blood vessel.
At the meeting, panelists are expected to discuss whether FDA approvals or recommendations for stent use should be changed based on how severe a patient's condition is, whether the patient is diabetic or otherwise belongs to a high-risk group, according to briefing documents posted on the agency's Web site.
The panel is also expected to discuss how long patients should take blood thinners like Bristol-Myers Squibb (BMY) and Sanofi-Aventis' (SNY) blockbuster drug Plavix after stents are implanted, another measure that doctors use to prevent artery re-clogging.
"The panel could take some steps toward quantifying what the problem may or may not be and possible solutions," says Steve Brozak, health care analyst at investment research firm WBB Securities. On whether drug companies could benefit from greater use of their treatments as stent use potentially declines, he says, "This could be a game where you see a decline but you don't see someone else benefiting from the decline."
In order to determine what measures to take on stents, the FDA panel will consider data, and possibly request more, on whether the use of drug-eluting stents is associated with an increased rate of death compared with stents made of bare metal.
Another concern, which could have a short-term impact on the companies' stocks, is the question of whether safety concerns apply to both Johnson & Johnson's Cypher stent and Boston Scientific's Taxus. The companies are fierce competitors for stent market share and are in constant battle with data supporting that each company's stent is superior to the other's.
For example, study results presented at the Transcatheter Cardiovascular Therapuetics conference in October showed that, after a year, J&J's stent was associated with a 0.6% risk of artery reclogging compared with no risk for bare-metal stents, and Boston's device led to a so-called late-stent-thrombosis rate of 0.7% vs. 0.2% in bare-metal stents.
But regardless of which stent is shown to cause more of a risk of reclogging, and even if the FDA panel recommends the equivalent of a black box warning about the device's safety, "it's not so much what the panel is going to do. It's what the payers and managed care companies are going to do" in response to the meeting's outcome, says Les Funtleyder, health care analyst at institutional trading firm Miller Tabak. The FDA issues black box warnings when studies show that a drug carries a significant risk of serious, possibly life-threatening, side effects.
Funtleyder says managed care companies will take a closer look at data, specifically the health risk tradeoff between drug-coated and bare stents, to determine whether to change authorization requirements for use of the devices. The analyst expects to see decreased use of drug-eluting stents in favor of the bare devices, and notes that both companies' DES sales have already lost out to bare-metal stents by a few percentage points of market share.
At the panel meeting, "there will be a lot of rhetoric from people who believe they're more dangerous, which may weigh on the stocks," Funtleyder says. But he believes that for the most part, safety concerns are already priced in.
The meeting could remove some uncertainty surrounding the safety concerns, and eventually lead to a response from the FDA and managed care companies' responses, but ultimately, "getting it over with will be helpful to the stocks and the whole medical device group," the analyst says. "I don't see much of a negative coming out of the meeting, and in the absence of a negative, I suppose it would be a positive."
Specialists on the FDA circulatory system devices panel will meet Thursday and Friday to review safety data, conduct public hearings and determine whether the stent makers will be required to submit additional safety data on their devices.
Some stents, which are used to prop open arteries cleared of plaque, are coated with drugs designed to prevent regrowth of tissue in the area where the device is implanted. But recent studies have found that the polymers that enable the slow release of drugs remain after all active ingredients are absorbed. Scientists worry they could cause a reaction by the immune system, leading to tissue regrowth within the blood vessel.
At the meeting, panelists are expected to discuss whether FDA approvals or recommendations for stent use should be changed based on how severe a patient's condition is, whether the patient is diabetic or otherwise belongs to a high-risk group, according to briefing documents posted on the agency's Web site.
The panel is also expected to discuss how long patients should take blood thinners like Bristol-Myers Squibb (BMY) and Sanofi-Aventis' (SNY) blockbuster drug Plavix after stents are implanted, another measure that doctors use to prevent artery re-clogging.
"The panel could take some steps toward quantifying what the problem may or may not be and possible solutions," says Steve Brozak, health care analyst at investment research firm WBB Securities. On whether drug companies could benefit from greater use of their treatments as stent use potentially declines, he says, "This could be a game where you see a decline but you don't see someone else benefiting from the decline."
In order to determine what measures to take on stents, the FDA panel will consider data, and possibly request more, on whether the use of drug-eluting stents is associated with an increased rate of death compared with stents made of bare metal.
Another concern, which could have a short-term impact on the companies' stocks, is the question of whether safety concerns apply to both Johnson & Johnson's Cypher stent and Boston Scientific's Taxus. The companies are fierce competitors for stent market share and are in constant battle with data supporting that each company's stent is superior to the other's.
For example, study results presented at the Transcatheter Cardiovascular Therapuetics conference in October showed that, after a year, J&J's stent was associated with a 0.6% risk of artery reclogging compared with no risk for bare-metal stents, and Boston's device led to a so-called late-stent-thrombosis rate of 0.7% vs. 0.2% in bare-metal stents.
But regardless of which stent is shown to cause more of a risk of reclogging, and even if the FDA panel recommends the equivalent of a black box warning about the device's safety, "it's not so much what the panel is going to do. It's what the payers and managed care companies are going to do" in response to the meeting's outcome, says Les Funtleyder, health care analyst at institutional trading firm Miller Tabak. The FDA issues black box warnings when studies show that a drug carries a significant risk of serious, possibly life-threatening, side effects.
Funtleyder says managed care companies will take a closer look at data, specifically the health risk tradeoff between drug-coated and bare stents, to determine whether to change authorization requirements for use of the devices. The analyst expects to see decreased use of drug-eluting stents in favor of the bare devices, and notes that both companies' DES sales have already lost out to bare-metal stents by a few percentage points of market share.
At the panel meeting, "there will be a lot of rhetoric from people who believe they're more dangerous, which may weigh on the stocks," Funtleyder says. But he believes that for the most part, safety concerns are already priced in.
The meeting could remove some uncertainty surrounding the safety concerns, and eventually lead to a response from the FDA and managed care companies' responses, but ultimately, "getting it over with will be helpful to the stocks and the whole medical device group," the analyst says. "I don't see much of a negative coming out of the meeting, and in the absence of a negative, I suppose it would be a positive."
Safety of Drug-Coated Stents Spotlighted
The two manufacturers of drug-coated stents used to prop open the arteries of about 3 million people in the U.S. say the devices' benefits outweigh their risks, even though patients could face a small but significant risk of blood clots.
The companies, Boston Scientific Corp. and Johnson & Johnson, are in the hot seat as the Food and Drug Administration begins two days of meetings on Thursday to discuss the clotting risks associated with the devices.
Some people believe that clotting leads to an increased risk of heart attack and death a danger the FDA said is unknown.
Boston Scientific acknowledges a slight increase in clotting associated with its drug-coated stent, the Taxus. The company said it has seen no corresponding increase in heart attacks or deaths.
Johnson & Johnson said there is 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 when compared to bare-metal stents. That accounts for the widespread use of the drug-coated versions since their introduction in 2003.
The FDA is looking to an outside panel of experts for advice on a wide range of questions on the drug-coated stents, including whether to update the labels with new warnings, identify patients for whom they are not appropriate and perhaps change federal recommendations on how long people should take anti-clotting drugs such as Plavix and aspirin following stent surgery.
The agency also seeks recommendations for research on drug-coated stents on the market or pending approval.
"This is a public health issue of great importance," FDA devices chief Dr. Daniel Schultz told reporters this week.
Multiple studies have suggested the risk of blood clots, heart attack and death rises in patients who stop taking Plavix earlier than now recommended. Some doctors recommend patients stay on it indefinitely until more is learned.
But FDA staff said it is unknown how long patients should take the drug, distributed by Bristol-Myers Squibb Co. and Sanofi-Aventis SA.
The companies, Boston Scientific Corp. and Johnson & Johnson, are in the hot seat as the Food and Drug Administration begins two days of meetings on Thursday to discuss the clotting risks associated with the devices.
Some people believe that clotting leads to an increased risk of heart attack and death a danger the FDA said is unknown.
Boston Scientific acknowledges a slight increase in clotting associated with its drug-coated stent, the Taxus. The company said it has seen no corresponding increase in heart attacks or deaths.
Johnson & Johnson said there is 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 when compared to bare-metal stents. That accounts for the widespread use of the drug-coated versions since their introduction in 2003.
The FDA is looking to an outside panel of experts for advice on a wide range of questions on the drug-coated stents, including whether to update the labels with new warnings, identify patients for whom they are not appropriate and perhaps change federal recommendations on how long people should take anti-clotting drugs such as Plavix and aspirin following stent surgery.
The agency also seeks recommendations for research on drug-coated stents on the market or pending approval.
"This is a public health issue of great importance," FDA devices chief Dr. Daniel Schultz told reporters this week.
Multiple studies have suggested the risk of blood clots, heart attack and death rises in patients who stop taking Plavix earlier than now recommended. Some doctors recommend patients stay on it indefinitely until more is learned.
But FDA staff said it is unknown how long patients should take the drug, distributed by Bristol-Myers Squibb Co. and Sanofi-Aventis SA.
Wednesday, December 6, 2006
The heart of a stent debate
Michael Young had a choice.
Doctors could clear his three blocked coronary arteries by cracking open his chest and surgically bypassing them. Or they could clear them from within by inflating a tiny balloon and propping them open with wire-mesh stents, coated with a drug to keep the arteries from closing again.
But drug-coated stents can be risky, too. New studies show that people with drug-coated stents who stop taking their anti-clotting medication — now recommended for just three to six months — are prone to rare but potentially fatal blood clots for years.
Young, 62, was aware of the risks, but when his surgeon told him that the less-traumatic procedure would be "adequate," he decided that it was the way to go.
"I decided to put myself in the hands of my doctors," says Young, a real estate broker from Providence. He had two of his arteries treated Nov. 16. He's due to have the third fixed soon.
But even doctors are divided about the safety of the tiny devices now implanted in about 6 million people worldwide. The debate is so contentious, and doctors are so uncertain what to do, that the Food and Drug Administration will convene a panel of experts for a two-day meeting Thursday and Friday in Gaithersburg, Md., to determine whether the agency should revise its guidelines for the $6 billion-a-year stent market.
"The FDA is doing the absolute right thing," says cardiologist and stent expert Judith Hochman of New York University School of Medicine.
Mixed signals
The market has exploded in the past two decades, says Donald Baim, chief medical officer of stent manufacturer Boston Scientific. Today, about 1 million people a year have angioplasty, compared with 300,000 who have bypass operations. About 600,000 angioplasty patients receive stents, doctors say.
"We have a technology that has really changed the way medicine is practiced," says Daniel Schultz, director of the FDA's Center for Devices and Radiological Health. "We're also getting signals that there is, in fact, a risk that may be higher than we had seen in the initial clinical trials."
The problem is new and the studies are difficult to interpret, so doctors aren't sure how widespread it is.
An analysis by Deepak Bhatt of Cleveland Clinic published last week in the American Journal of Medicine suggests that the risk of developing a blood clot may be up to five times higher for patients with drug-coated stents than for those with bare-metal stents. A study released in October by Gregg Stone and Martin Leon of the Cardiovascular Research Foundation pegged the risk at about 0.5% a year — or five for every 1,000 drug-coated stent patients.
"There's continuing uncertainty as to what the true risk really is," says Robert Bonow, chief of cardiology at Northwestern University.
To reduce the risk of clots, the FDA recommends that patients stay on anti-clotting medicines, aspirin and clopidogrel (sold as Plavix), for three to six months after the stents are put in. Most blood clots appear months to years after the stents are in place, suggesting that patients should take the two medicines much longer.
As a precaution, some doctors, including Bonow and David Williams of Rhode Island Hospital, recommend patients take Plavix for a much longer period. But not everyone agrees. Although Plavix, the second-leading seller of all drugs in the USA, has been shown to be relatively safe, it can cause bleeding, especially in patients who have ulcers or have surgery, Stone says, and it's also costly.
"You've got 6 million patients worldwide, and the drug costs about $4 a day. That's about $24 million a day," he says. "On top of that, every year you're treating another million or so patients. It's not impossible to spend that kind of money, but we have to know that it's safe and it works. Right now we don't."
But the risks of not taking Plavix long-term may be higher, a study in today's Journal of the American Medical Association reports. In the study of more than 4,600 patients, researchers found that those who stopped taking Plavix from six months to a year after their drug-coated stents were put in place were more than twice as likely to die or have a heart attack than those who stayed on their medication.
"One of the striking things about our study is that we didn't see any point at which the risk diminished," says lead author Robert Califf of Duke University.
'Two sides to every story'
The irony is that drug-coated stents were developed to counter a side effect commonly seen with bare-metal stents: the regrowth of tissue within the artery that shuts it down again. Patients may find themselves experiencing the same symptoms that led to angioplasty in the first place. Some may need a repeat angioplasty or a bypass operation.
For the most part, some doctors argue, the symptoms of tissue regrowth are relatively benign, while a blood clot can cause a heart attack. "We're talking about significant heart damage that can be fatal," says Williams, who performed Young's angioplasty.
But there's disagreement here, too. Stone asserts that new studies suggest that, in 3% to 19% of cases, re-clogged arteries make themselves known by causing a heart attack. He argues that the risk of a blood clot and the risk of re-narrowing balance out. "As in everything in life," he says, "there are two sides to every story."
Hence FDA's decision to hold an advisory committee meeting. "We want to … get all of the data that's currently available on the table in a neutral setting, where there isn't a bias one way or another."
The agency's recommendations, he says, "will depend on the level of consensus and where the discussion ends up taking us."
Doctors could clear his three blocked coronary arteries by cracking open his chest and surgically bypassing them. Or they could clear them from within by inflating a tiny balloon and propping them open with wire-mesh stents, coated with a drug to keep the arteries from closing again.
But drug-coated stents can be risky, too. New studies show that people with drug-coated stents who stop taking their anti-clotting medication — now recommended for just three to six months — are prone to rare but potentially fatal blood clots for years.
Young, 62, was aware of the risks, but when his surgeon told him that the less-traumatic procedure would be "adequate," he decided that it was the way to go.
"I decided to put myself in the hands of my doctors," says Young, a real estate broker from Providence. He had two of his arteries treated Nov. 16. He's due to have the third fixed soon.
But even doctors are divided about the safety of the tiny devices now implanted in about 6 million people worldwide. The debate is so contentious, and doctors are so uncertain what to do, that the Food and Drug Administration will convene a panel of experts for a two-day meeting Thursday and Friday in Gaithersburg, Md., to determine whether the agency should revise its guidelines for the $6 billion-a-year stent market.
"The FDA is doing the absolute right thing," says cardiologist and stent expert Judith Hochman of New York University School of Medicine.
Mixed signals
The market has exploded in the past two decades, says Donald Baim, chief medical officer of stent manufacturer Boston Scientific. Today, about 1 million people a year have angioplasty, compared with 300,000 who have bypass operations. About 600,000 angioplasty patients receive stents, doctors say.
"We have a technology that has really changed the way medicine is practiced," says Daniel Schultz, director of the FDA's Center for Devices and Radiological Health. "We're also getting signals that there is, in fact, a risk that may be higher than we had seen in the initial clinical trials."
The problem is new and the studies are difficult to interpret, so doctors aren't sure how widespread it is.
An analysis by Deepak Bhatt of Cleveland Clinic published last week in the American Journal of Medicine suggests that the risk of developing a blood clot may be up to five times higher for patients with drug-coated stents than for those with bare-metal stents. A study released in October by Gregg Stone and Martin Leon of the Cardiovascular Research Foundation pegged the risk at about 0.5% a year — or five for every 1,000 drug-coated stent patients.
"There's continuing uncertainty as to what the true risk really is," says Robert Bonow, chief of cardiology at Northwestern University.
To reduce the risk of clots, the FDA recommends that patients stay on anti-clotting medicines, aspirin and clopidogrel (sold as Plavix), for three to six months after the stents are put in. Most blood clots appear months to years after the stents are in place, suggesting that patients should take the two medicines much longer.
As a precaution, some doctors, including Bonow and David Williams of Rhode Island Hospital, recommend patients take Plavix for a much longer period. But not everyone agrees. Although Plavix, the second-leading seller of all drugs in the USA, has been shown to be relatively safe, it can cause bleeding, especially in patients who have ulcers or have surgery, Stone says, and it's also costly.
"You've got 6 million patients worldwide, and the drug costs about $4 a day. That's about $24 million a day," he says. "On top of that, every year you're treating another million or so patients. It's not impossible to spend that kind of money, but we have to know that it's safe and it works. Right now we don't."
But the risks of not taking Plavix long-term may be higher, a study in today's Journal of the American Medical Association reports. In the study of more than 4,600 patients, researchers found that those who stopped taking Plavix from six months to a year after their drug-coated stents were put in place were more than twice as likely to die or have a heart attack than those who stayed on their medication.
"One of the striking things about our study is that we didn't see any point at which the risk diminished," says lead author Robert Califf of Duke University.
'Two sides to every story'
The irony is that drug-coated stents were developed to counter a side effect commonly seen with bare-metal stents: the regrowth of tissue within the artery that shuts it down again. Patients may find themselves experiencing the same symptoms that led to angioplasty in the first place. Some may need a repeat angioplasty or a bypass operation.
For the most part, some doctors argue, the symptoms of tissue regrowth are relatively benign, while a blood clot can cause a heart attack. "We're talking about significant heart damage that can be fatal," says Williams, who performed Young's angioplasty.
But there's disagreement here, too. Stone asserts that new studies suggest that, in 3% to 19% of cases, re-clogged arteries make themselves known by causing a heart attack. He argues that the risk of a blood clot and the risk of re-narrowing balance out. "As in everything in life," he says, "there are two sides to every story."
Hence FDA's decision to hold an advisory committee meeting. "We want to … get all of the data that's currently available on the table in a neutral setting, where there isn't a bias one way or another."
The agency's recommendations, he says, "will depend on the level of consensus and where the discussion ends up taking us."
Heart stents examined by FDA
Stents, tiny latticework like tubes that hold open clogged arteries have revolutionized the treatment of heart disease, enabling millions people to avoid bypass surgery.
But now the newest models, coated with drugs, are under the government microscope.
"Are you doing a drug eluting stent or a bare stent?"
Its estimated more than six million people have received drug-eluting stents, tube-like props coated with medicines as an extra measure to prevent arteries from clogging.
"Ok, we're going to stent boost"
Now the FDA is examining the safety of the coated stents amid growing research suggesting a risk of clotting one to three years after they are implanted.
"We did find a higher rate of stents clotting up with longer term follow-up with drug coated stents v bare metal stents," said Cleveland Clinic cardiologist and researcher Deepak Bhatt.
According to federal statistics, late stage clotting happens in three to four out of every thousand patients.
The Cleveland Clinic's Dr. Deepak Bhatt notes that while such findings raise a red flag they should not trigger panic.
"So the absolute risk to an individual patient is quite low, unless of course you happen to be that patient. So it's not an altogether trivial issue but should not be the cause for panic among either patients or their physicians, said Deepak.
A statement by the American Heart Association highlights research suggesting that poor patient compliance with follow-up drug therapy either blood thinners or long-term aspirin therapy plays a role. An FDA committee will review all the research and decide whether further study or new warnings are needed.
One big question the FDA will address is how long patients need to stay on blood thinning drugs after they get a drug-coated stint. Labels on the stints currently recommend six months.
But a study released this week out of Duke University found an increased risk of clots even in patients who stayed on blood thinning medicine for up to a year.
It's estimated that stents are implanted in 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.
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.
But now the newest models, coated with drugs, are under the government microscope.
"Are you doing a drug eluting stent or a bare stent?"
Its estimated more than six million people have received drug-eluting stents, tube-like props coated with medicines as an extra measure to prevent arteries from clogging.
"Ok, we're going to stent boost"
Now the FDA is examining the safety of the coated stents amid growing research suggesting a risk of clotting one to three years after they are implanted.
"We did find a higher rate of stents clotting up with longer term follow-up with drug coated stents v bare metal stents," said Cleveland Clinic cardiologist and researcher Deepak Bhatt.
According to federal statistics, late stage clotting happens in three to four out of every thousand patients.
The Cleveland Clinic's Dr. Deepak Bhatt notes that while such findings raise a red flag they should not trigger panic.
"So the absolute risk to an individual patient is quite low, unless of course you happen to be that patient. So it's not an altogether trivial issue but should not be the cause for panic among either patients or their physicians, said Deepak.
A statement by the American Heart Association highlights research suggesting that poor patient compliance with follow-up drug therapy either blood thinners or long-term aspirin therapy plays a role. An FDA committee will review all the research and decide whether further study or new warnings are needed.
One big question the FDA will address is how long patients need to stay on blood thinning drugs after they get a drug-coated stint. Labels on the stints currently recommend six months.
But a study released this week out of Duke University found an increased risk of clots even in patients who stayed on blood thinning medicine for up to a year.
It's estimated that stents are implanted in 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.
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.
Drug-coated stents facing hard 2d look
A Food and Drug Administration panel tomorrow will consider one of the most urgent questions in medicine: what to do about the risk of blood clots caused by drug-coated stents, tiny medical devices implanted in the arteries of millions of people.
The topic of clots has headlined national medical conferences and filled the pages of medical journals. Now it will be discussed by 19 specialists during a two-day FDA hearing in Maryland.
Behind the clotting concerns, a second issue has emerged about drug-coated stents: A small but vocal group of doctors say the devices, which cost about $2,000 apiece, may be only marginally more effective than the cheaper bare-metal stents they replaced.
Some doctors and public-health experts have begun to see the tiny mesh tubes not just as an example of a profitable fusion of drug and medical device, but as a lesson in how doctors can be seduced by an appealing new idea backed by powerful salesmanship.
Cynthia Yock, a healthcare researcher at Stanford University who has analyzed the research on drug-coated stents, calls their popularity "a fantastic case study of the companies being able to expand the market in advance of the true clinical need."
Since their arrival in 2003, drug-coated stents have become the fastest-selling medical device ever. Doctors' confidence in their benefits helped Natick stent maker Boston Scientific Corp. generate more than $2 billion annually from stent sales, growing the company into one of the world's medical-device giants.
But as evidence mounts that drug-coated stents cause dangerous blood clots in a small number of patients, cardiology leaders are taking a hard look at the benefits that led them to choose them over the older generation of bare-metal stents.
Stents hold coronary arteries open after they have been cleared of a blockage. In the clinical trial that won approval for the first drug-coated stent, Johnson & Johnson showed that 21 percent of patients who got older bare-metal stents required a repeat procedure because their arteries had re narrowed. Drug-eluting stents brought that number down to 5 percent. Boston Scientific's approval trial showed a similar drop, from 15 percent in bare-metal stents to 4 percent in drug-eluting stents.
Some newer studies show older stents may not perform as badly as suggested by those earlier trials.
An analysis published in August of more than 17,000 patients treated at 17 hospitals in the United States found just 8 percent of patients who received bare-metal stents needed to return for an artery-clearing procedure.
"In current real-life practice, bare-metal stents aren't performing as poorly as we thought they performed, and it's a bit sobering to see that," said Deepak Bhatt, a cardiologist at the Cleveland Clinic who was not involved in the analysis.
A Boston Scientific spokesman said the benefits of its Taxus stent "have been maintained in real-world use," and the company plans to back its claims by giving the FDA panel data from a global registry of 7,000 stent patients.
Dr. Sanjay Kaul, a cardiologist at Cedars-Sinai Medical Center in Los Angeles, has emerged as a critic of the widespread use of drug-eluting stents. He said the original approval trials ultimately created an exaggerated picture of the risks of bare-metal stents. The models used for comparison in the trials weren't state-of-the art, Kaul said. More importantly, he said, all patients in the trials received a mandatory angiogram, a diagnostic procedure to measure blood flow. Doctors are more likely to re intervene after seeing some artery narrowing in an angiogram, even if the patient has no symptoms.
"It's a classic example of how you stack the deck in favor of your therapy in clinical trials," Kaul said.
The FDA panel will review numerous studies of stents and listen to presentations by doctors and stent manufacturers. Its chief goal is to determine how likely drug-eluting stents are to cause long-term blood clots, and what should be done. Bhatt last week published a study saying drug-coated stents are likely to trigger a blockage in about one in 200 patients -- five times the rate of clotting in bare-metal stents.
A paper released online yesterday by the Journal of the American Medical Association suggests patients can reduce their risk of clotting by staying on the blood-thinning drug Plavix, but blood-thinners have complications, including a higher risk of bleeding.
The FDA is also looking at whether drug-coated stents solve a major health problem. Studies consistently show patients are less likely to have re narrowed arteries with a drug-coated stent. But many doctors are questioning whether that is worth the risk of clotting, since re narrowed arteries rarely lead to serious problems such as heart attacks.
"You have a trade-off," said Robert Califf, a Duke University cardiologist, who was the lead author of yesterday's JAMA article. "You have a less frequent, more severe risk, and a more frequent, less important benefit."
For some cardiologists, the debate has triggered a re examination of why drug-coated stents were adopted before long-term safety data became available.
Fueled by high-profile early studies and a strong sales and advertising push by manufacturers, the stents quickly captured the market.
Within two years of introduction they were used in 90 percent of procedures, even though they were technically approved only for patients with relatively simple coronary artery problems.
"If I were to teach a course in marketing," said Kaul, "I certainly would use this as an example."
The topic of clots has headlined national medical conferences and filled the pages of medical journals. Now it will be discussed by 19 specialists during a two-day FDA hearing in Maryland.
Behind the clotting concerns, a second issue has emerged about drug-coated stents: A small but vocal group of doctors say the devices, which cost about $2,000 apiece, may be only marginally more effective than the cheaper bare-metal stents they replaced.
Some doctors and public-health experts have begun to see the tiny mesh tubes not just as an example of a profitable fusion of drug and medical device, but as a lesson in how doctors can be seduced by an appealing new idea backed by powerful salesmanship.
Cynthia Yock, a healthcare researcher at Stanford University who has analyzed the research on drug-coated stents, calls their popularity "a fantastic case study of the companies being able to expand the market in advance of the true clinical need."
Since their arrival in 2003, drug-coated stents have become the fastest-selling medical device ever. Doctors' confidence in their benefits helped Natick stent maker Boston Scientific Corp. generate more than $2 billion annually from stent sales, growing the company into one of the world's medical-device giants.
But as evidence mounts that drug-coated stents cause dangerous blood clots in a small number of patients, cardiology leaders are taking a hard look at the benefits that led them to choose them over the older generation of bare-metal stents.
Stents hold coronary arteries open after they have been cleared of a blockage. In the clinical trial that won approval for the first drug-coated stent, Johnson & Johnson showed that 21 percent of patients who got older bare-metal stents required a repeat procedure because their arteries had re narrowed. Drug-eluting stents brought that number down to 5 percent. Boston Scientific's approval trial showed a similar drop, from 15 percent in bare-metal stents to 4 percent in drug-eluting stents.
Some newer studies show older stents may not perform as badly as suggested by those earlier trials.
An analysis published in August of more than 17,000 patients treated at 17 hospitals in the United States found just 8 percent of patients who received bare-metal stents needed to return for an artery-clearing procedure.
"In current real-life practice, bare-metal stents aren't performing as poorly as we thought they performed, and it's a bit sobering to see that," said Deepak Bhatt, a cardiologist at the Cleveland Clinic who was not involved in the analysis.
A Boston Scientific spokesman said the benefits of its Taxus stent "have been maintained in real-world use," and the company plans to back its claims by giving the FDA panel data from a global registry of 7,000 stent patients.
Dr. Sanjay Kaul, a cardiologist at Cedars-Sinai Medical Center in Los Angeles, has emerged as a critic of the widespread use of drug-eluting stents. He said the original approval trials ultimately created an exaggerated picture of the risks of bare-metal stents. The models used for comparison in the trials weren't state-of-the art, Kaul said. More importantly, he said, all patients in the trials received a mandatory angiogram, a diagnostic procedure to measure blood flow. Doctors are more likely to re intervene after seeing some artery narrowing in an angiogram, even if the patient has no symptoms.
"It's a classic example of how you stack the deck in favor of your therapy in clinical trials," Kaul said.
The FDA panel will review numerous studies of stents and listen to presentations by doctors and stent manufacturers. Its chief goal is to determine how likely drug-eluting stents are to cause long-term blood clots, and what should be done. Bhatt last week published a study saying drug-coated stents are likely to trigger a blockage in about one in 200 patients -- five times the rate of clotting in bare-metal stents.
A paper released online yesterday by the Journal of the American Medical Association suggests patients can reduce their risk of clotting by staying on the blood-thinning drug Plavix, but blood-thinners have complications, including a higher risk of bleeding.
The FDA is also looking at whether drug-coated stents solve a major health problem. Studies consistently show patients are less likely to have re narrowed arteries with a drug-coated stent. But many doctors are questioning whether that is worth the risk of clotting, since re narrowed arteries rarely lead to serious problems such as heart attacks.
"You have a trade-off," said Robert Califf, a Duke University cardiologist, who was the lead author of yesterday's JAMA article. "You have a less frequent, more severe risk, and a more frequent, less important benefit."
For some cardiologists, the debate has triggered a re examination of why drug-coated stents were adopted before long-term safety data became available.
Fueled by high-profile early studies and a strong sales and advertising push by manufacturers, the stents quickly captured the market.
Within two years of introduction they were used in 90 percent of procedures, even though they were technically approved only for patients with relatively simple coronary artery problems.
"If I were to teach a course in marketing," said Kaul, "I certainly would use this as an example."
Tuesday, December 5, 2006
FDA: Stent patients face blood clot risk
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.
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.
Controversy Swirls Around FDA Meeting on Stents
A planned FDA safety review regarding the use of drug-coated stents is facing intense scrutiny after it was revealed that six doctors on the advisory panel have financial links to stent makers Johnson & Johnson and Boston Scientific. The meeting, set for Thursday and Friday of this week, has been scheduled in order to discuss significant risks of blood clotting associated with the use of drug-coated stents. The FDA granted conflict-of-interest waivers to all six of the physicians in question.
In advance of the meeting, the FDA released documents today related to an FDA staff review that noted that the drug-coated stents “are associated with a small but significant risk of late-stent thrombosis.” Stents are wire-mesh devices used to unclog arteries. The drug-coated stents are intended to prevent scar tissue from forming in the arteries, but preliminary research has determined that the coated stents may increase the probability of adverse events, including heart attacks and strokes.
Agency critics are amazed and appalled that the FDA would allow panel members with significant ties to the companies whose devices are being reviewed. In a statement last month, Merrill Goozner of the Center for Science in the Public Interest said, “The scientists who advise the FDA should be free of all financial ties to firms whose products are under review. The public’s faith in the integrity of the process will be undermined by any reform legislation that allows physicians and scientists with conflicts of interest to continue serving on these committees.”
In response to the latest controversy, Goozner told the Newark Star-Ledger: “There are literally thousands of experts all over this country who are well-schooled in the details of this field. But instead of reaching out to that community to get a totally unbiased look at this question, the FDA appointed a committee on which a substantial fraction have conflicts of interest directly with manufacturers of products being evaluated. It’s almost impossible to have confidence in the outcomes of this kind of deliberation.”
According to Bloomberg News, one member of the advisory panel is Robert Harrington, who runs a Duke University research institute funded by both J&J and Boston Scientific.
Drug-coated stents have been used in 4 million patients and have sales in the $6 billion range annually. They are significantly more expensive than bare stents, but apparently they are more dangerous as well.
In advance of the meeting, the FDA released documents today related to an FDA staff review that noted that the drug-coated stents “are associated with a small but significant risk of late-stent thrombosis.” Stents are wire-mesh devices used to unclog arteries. The drug-coated stents are intended to prevent scar tissue from forming in the arteries, but preliminary research has determined that the coated stents may increase the probability of adverse events, including heart attacks and strokes.
Agency critics are amazed and appalled that the FDA would allow panel members with significant ties to the companies whose devices are being reviewed. In a statement last month, Merrill Goozner of the Center for Science in the Public Interest said, “The scientists who advise the FDA should be free of all financial ties to firms whose products are under review. The public’s faith in the integrity of the process will be undermined by any reform legislation that allows physicians and scientists with conflicts of interest to continue serving on these committees.”
In response to the latest controversy, Goozner told the Newark Star-Ledger: “There are literally thousands of experts all over this country who are well-schooled in the details of this field. But instead of reaching out to that community to get a totally unbiased look at this question, the FDA appointed a committee on which a substantial fraction have conflicts of interest directly with manufacturers of products being evaluated. It’s almost impossible to have confidence in the outcomes of this kind of deliberation.”
According to Bloomberg News, one member of the advisory panel is Robert Harrington, who runs a Duke University research institute funded by both J&J and Boston Scientific.
Drug-coated stents have been used in 4 million patients and have sales in the $6 billion range annually. They are significantly more expensive than bare stents, but apparently they are more dangerous as well.
Boston Scientific Widens Stent Recall
Boston Scientific announced that it was expanding a recall of Taxus stents, a heart treatment device and one of its biggest products, forcing it to delay the release of second-quarter earnings by a week and resulting in a large charge for inventory write-downs.
On July 2, Boston Scientific announced that it was recalling 200 Taxus stent systems, which are used after balloon angioplasty procedures to keep arteries open once blockages are cleared. But after some production runs of the Taxus Express 2 stent blocked the balloon's ability to deflate, the company announced that it was recalling 200 units and re-examined the manufacturing of the device, which was approved by the Food & Drug Administration in March.
After further analysis, the company said that other production lots of both its bare metal and drug-eluting versions of Taxus, which share the same kind of catheter, may have similar manufacturing defects. The company is now widening its voluntary recall to cover 85,000 Taxus systems and 11,000 Taxus Express 2 systems, all of which were made at factories in Galway, Ireland and Maple Grove, Minn.
"While the number of customer reports of balloon deflation difficulty is extremely small, patient safety is the company's paramount concern, and therefore it has chosen to initiate this broader recall," said Boston Scientific, in a statement.
While Boston Scientific downplayed the number of people affected by the stent malfunctions, the company said that the device was already responsible for one death and 18 serious injuries in the case of the drug-coated version of Taxus, with two deaths and 25 serious injuries for the bare-metal version.
The news is a major setback for Boston Scientific, whose stent was already beginning to seize market share from Johnson & Johnson after just four months on the market. In the second quarter, Johnson & Johnson said that sales of its Cypher stent had just 30% of the market it dominated a year earlier as the first treatment on the market. Already, Boston Scientific has shipped more than 500,000 Taxus stent systems and 600,000 Express 2 systems.
Going forward, the company said that current and future production runs would not be affected by the recall, but did say that the decision will reverse $45 million in sales already booked and force it to take a $50 million write-down for inventory. It will also be postponing its second-quarter earnings release, originally scheduled to be released this Monday, to July 26, a week later.
On July 2, Boston Scientific announced that it was recalling 200 Taxus stent systems, which are used after balloon angioplasty procedures to keep arteries open once blockages are cleared. But after some production runs of the Taxus Express 2 stent blocked the balloon's ability to deflate, the company announced that it was recalling 200 units and re-examined the manufacturing of the device, which was approved by the Food & Drug Administration in March.
After further analysis, the company said that other production lots of both its bare metal and drug-eluting versions of Taxus, which share the same kind of catheter, may have similar manufacturing defects. The company is now widening its voluntary recall to cover 85,000 Taxus systems and 11,000 Taxus Express 2 systems, all of which were made at factories in Galway, Ireland and Maple Grove, Minn.
"While the number of customer reports of balloon deflation difficulty is extremely small, patient safety is the company's paramount concern, and therefore it has chosen to initiate this broader recall," said Boston Scientific, in a statement.
While Boston Scientific downplayed the number of people affected by the stent malfunctions, the company said that the device was already responsible for one death and 18 serious injuries in the case of the drug-coated version of Taxus, with two deaths and 25 serious injuries for the bare-metal version.
The news is a major setback for Boston Scientific, whose stent was already beginning to seize market share from Johnson & Johnson after just four months on the market. In the second quarter, Johnson & Johnson said that sales of its Cypher stent had just 30% of the market it dominated a year earlier as the first treatment on the market. Already, Boston Scientific has shipped more than 500,000 Taxus stent systems and 600,000 Express 2 systems.
Going forward, the company said that current and future production runs would not be affected by the recall, but did say that the decision will reverse $45 million in sales already booked and force it to take a $50 million write-down for inventory. It will also be postponing its second-quarter earnings release, originally scheduled to be released this Monday, to July 26, a week later.
Drawbacks of drug-coated stents surfacing
Doctors have begun to consider the drawbacks of coated stents, the tiny mesh devices implanted to prop open clogged arteries, in light of emerging studies revealing a risk of blood clots that can lead to heart attacks and strokes.
The era of the coated devices, which are known technically as drug-eluting stents, was ushered in amid fanfare just three years ago as doctors anticipated a more effective way of treating coronary artery disease. Drug coatings thwart the encroachment of immune system cells that can cause blood vessel scarring and replugging. Coated stents replaced bare metal ones, which left the patient vulnerable to re-blockage.
Two reports in today's New England Journal of Medicine document problems with coated stents, suggesting a return to the bare metal type for some newly diagnosed patients.
Last week a team of European doctors at the World Congress of Cardiology in Barcelona reported problems with dangerous blood clots, which appeared several years after patients had been implanted with a drug-coated device. And Boston Scientific, maker of a stent coated with the cancer drug paclitaxel and sold as the Taxus stent, acknowledged that their own data demonstrates a potential for abnormal clotting with the device.
"This is a classic kind of thing," said Dr. David Brown, chief of cardiovascular medicine at Stony Brook University Medical Center. "Every time we have a technological breakthrough, we invent a new disease along with it. In this case, it's late-stage thrombosis ."
Stenting became an option in the 1980s with the development of bare metal devices. In addition to Taxus, the Cypher stent, by Cordis, a division of Johnson & Johnson is coated with sirolimus, which also beats back cellular forces that lead to re-clogging. An estimated 6 million coated stents have been implanted worldwide
Dr. Steven Nissen, president of the American College of Cardiology and chairman of cardiovascular medicine at the Cleveland Clinic, said it's time to conduct a large-scale clinical trial to determine the risk for heart attacks, strokes and death with the coated devices. He underscored that the clinical trials leading to approval of the devices were not long enough.
"It's all about risks and benefits," Nissen said. "In this case, the late-stage thrombosis with drug-eluting stents is an unintended consequence. We're now beginning to get the big picture."
Even though Nissen told Newsday two years ago that stents would become passe as better drug treatments evolved, he said the newly identified problems are not a sign stents are fading out of favor. "These devices are still very important," in the treatment of heart patients, Nissen said.
Both he and Brown say one way to cope with drug-eluting stents is to extend the amount of time patients are on dual blood-thinning therapy aspirin and the drug Plavix. Even though all heart patients must take aspirin for life, they are weaned from Plavix. Patients with drug-coated stents may have to remain on the drugs longer.
"The decline in bypass surgery nationally occurred as a result of better medical therapy, so I don't think we'll see a shift from a percutaneous treatment to a surgical treatment," Dr. Kevin Marzo, chief of interventional cardiology at Winthrop-University Hospital in Mineola, said.
The era of the coated devices, which are known technically as drug-eluting stents, was ushered in amid fanfare just three years ago as doctors anticipated a more effective way of treating coronary artery disease. Drug coatings thwart the encroachment of immune system cells that can cause blood vessel scarring and replugging. Coated stents replaced bare metal ones, which left the patient vulnerable to re-blockage.
Two reports in today's New England Journal of Medicine document problems with coated stents, suggesting a return to the bare metal type for some newly diagnosed patients.
Last week a team of European doctors at the World Congress of Cardiology in Barcelona reported problems with dangerous blood clots, which appeared several years after patients had been implanted with a drug-coated device. And Boston Scientific, maker of a stent coated with the cancer drug paclitaxel and sold as the Taxus stent, acknowledged that their own data demonstrates a potential for abnormal clotting with the device.
"This is a classic kind of thing," said Dr. David Brown, chief of cardiovascular medicine at Stony Brook University Medical Center. "Every time we have a technological breakthrough, we invent a new disease along with it. In this case, it's late-stage thrombosis ."
Stenting became an option in the 1980s with the development of bare metal devices. In addition to Taxus, the Cypher stent, by Cordis, a division of Johnson & Johnson is coated with sirolimus, which also beats back cellular forces that lead to re-clogging. An estimated 6 million coated stents have been implanted worldwide
Dr. Steven Nissen, president of the American College of Cardiology and chairman of cardiovascular medicine at the Cleveland Clinic, said it's time to conduct a large-scale clinical trial to determine the risk for heart attacks, strokes and death with the coated devices. He underscored that the clinical trials leading to approval of the devices were not long enough.
"It's all about risks and benefits," Nissen said. "In this case, the late-stage thrombosis with drug-eluting stents is an unintended consequence. We're now beginning to get the big picture."
Even though Nissen told Newsday two years ago that stents would become passe as better drug treatments evolved, he said the newly identified problems are not a sign stents are fading out of favor. "These devices are still very important," in the treatment of heart patients, Nissen said.
Both he and Brown say one way to cope with drug-eluting stents is to extend the amount of time patients are on dual blood-thinning therapy aspirin and the drug Plavix. Even though all heart patients must take aspirin for life, they are weaned from Plavix. Patients with drug-coated stents may have to remain on the drugs longer.
"The decline in bypass surgery nationally occurred as a result of better medical therapy, so I don't think we'll see a shift from a percutaneous treatment to a surgical treatment," Dr. Kevin Marzo, chief of interventional cardiology at Winthrop-University Hospital in Mineola, said.
Monday, December 4, 2006
Boston Scientific admits stent risks
The U.S.-based Boston Scientific Corp. has admitted there is an increased risk of blood clots caused by use of its drug-coated cardiac stent.
The company, the leading stent seller in the nation says an analysis of clinical data reveals the increased risk of blood clots months after a stent is implanted, The Wall Street Journal reported, noting the announcement marks the first time any stent maker has acknowledged the heightened risk of side effects from using drug-coated stents.
Stents are small, wire-mesh tubes that are inserted into a blood vessel or other body structure to provide support and keep the structure open. The drugs used to coat some stents are designed to prevent growth of tissue after implantation.
The Journal said stent sales exceed $5 billion annually in a market dominated by Boston Scientific and Johnson & Johnson.
Boston Scientific, which has its headquarters in Natick, Mass., claims recent studies suggest both its Taxus brand of stent and J&J's Cypher stent present similar risks of late-occurring blood clots. J&J company officials, however, told the Journal they see no statistically significant risk of late thrombosis caused by their Cypher stents.
The company, the leading stent seller in the nation says an analysis of clinical data reveals the increased risk of blood clots months after a stent is implanted, The Wall Street Journal reported, noting the announcement marks the first time any stent maker has acknowledged the heightened risk of side effects from using drug-coated stents.
Stents are small, wire-mesh tubes that are inserted into a blood vessel or other body structure to provide support and keep the structure open. The drugs used to coat some stents are designed to prevent growth of tissue after implantation.
The Journal said stent sales exceed $5 billion annually in a market dominated by Boston Scientific and Johnson & Johnson.
Boston Scientific, which has its headquarters in Natick, Mass., claims recent studies suggest both its Taxus brand of stent and J&J's Cypher stent present similar risks of late-occurring blood clots. J&J company officials, however, told the Journal they see no statistically significant risk of late thrombosis caused by their Cypher stents.
Blood clots spur look at stents
Drug-coated heart stents will undergo review by a U.S. advisory panel by the end of the year after reports of blood-clotting associated with the devices.
The Food and Drug Administration said it intends to "more formally evaluate" studies that were presented at medical meetings in Atlanta and Barcelona, where Chicago-based Abbott Laboratories was among companies presenting data on the devices.
"Drug-eluting stents offer substantial clinical benefits to patients," Abbott spokesman Jonathan Hamilton said, a view echoed by the FDA.
The devices "remain safe and effective when used for the FDA approved indications," the FDA said in a Web posting announcing the review. "These devices have significantly reduced the need for a second surgery to treat" renarrowing of blood vessels for thousands of patients each year.
Boston Scientific last week said it found a small risk of blood clots developing inside its drug-coated heart stents months after doctors placed them in diseased blood vessels to keep them open. Johnson & Johnson says it hasn't found similar problems.
The Food and Drug Administration said it intends to "more formally evaluate" studies that were presented at medical meetings in Atlanta and Barcelona, where Chicago-based Abbott Laboratories was among companies presenting data on the devices.
"Drug-eluting stents offer substantial clinical benefits to patients," Abbott spokesman Jonathan Hamilton said, a view echoed by the FDA.
The devices "remain safe and effective when used for the FDA approved indications," the FDA said in a Web posting announcing the review. "These devices have significantly reduced the need for a second surgery to treat" renarrowing of blood vessels for thousands of patients each year.
Boston Scientific last week said it found a small risk of blood clots developing inside its drug-coated heart stents months after doctors placed them in diseased blood vessels to keep them open. Johnson & Johnson says it hasn't found similar problems.
Drug stents more likely to clot blood: analysis
Blood clotting is four to five times more likely in patients getting drug-coated heart devices known as stents, compared to the older bare-metal variety, according to a large data analysis released on Wednesday.
The analysis came one week before a U.S. Food and Drug Administration panel of experts is to meet to discuss the issue.
The Cleveland Clinic analysis of 14 studies with 6,675 patients will likely fuel a growing debate about the safety of drug-coated stents, the tiny wire-mesh devices used to prop open surgically cleared arteries.
Thrombosis, or blood clots, can lead to heart attacks.
The release of the study in the December issue of American Journal of Medicine came one week before the FDA panel is to discuss stent thrombosis, or potentially fatal blood clotting long after the devices are implanted.
"Our analysis found that there is a small, but real hazard of late stent thrombosis with drug-eluting stents more so than with bare-metal stents, likely in the setting of discontinuation of anti-clotting drugs," said Dr. Deepak Bhatt, a Cleveland Clinic official, in a prepared statement.
"This does not mean that drug-eluting stents should not be used, as other studies have shown that they do significantly reduce the need for repeat procedures compared with bare metal stents," added Bhatt, associate director of the Cleveland Clinic Cardiovascular Coordinating Center and one of the study's authors.
Shares of companies that manufacture drug-eluting stents have fallen in recent days amid concern the FDA panel will highlight the risks of the medical devices.
The analysis came one week before a U.S. Food and Drug Administration panel of experts is to meet to discuss the issue.
The Cleveland Clinic analysis of 14 studies with 6,675 patients will likely fuel a growing debate about the safety of drug-coated stents, the tiny wire-mesh devices used to prop open surgically cleared arteries.
Thrombosis, or blood clots, can lead to heart attacks.
The release of the study in the December issue of American Journal of Medicine came one week before the FDA panel is to discuss stent thrombosis, or potentially fatal blood clotting long after the devices are implanted.
"Our analysis found that there is a small, but real hazard of late stent thrombosis with drug-eluting stents more so than with bare-metal stents, likely in the setting of discontinuation of anti-clotting drugs," said Dr. Deepak Bhatt, a Cleveland Clinic official, in a prepared statement.
"This does not mean that drug-eluting stents should not be used, as other studies have shown that they do significantly reduce the need for repeat procedures compared with bare metal stents," added Bhatt, associate director of the Cleveland Clinic Cardiovascular Coordinating Center and one of the study's authors.
Shares of companies that manufacture drug-eluting stents have fallen in recent days amid concern the FDA panel will highlight the risks of the medical devices.
Heart Stents Reconsidered by Medical Community
For the better part of the last decade, heart stents have been celebrated as one of the most important developments in the medical field, and, with sales of heart stents reaching $6 billion annually, it’s also been one of the fastest-growing segments of the industry. Yet, it seems with each passing day that more and more questions arise regarding their long-term safety.
Recent evidence points to an increased risk of fatal blood clotting associated with a particular type of stent, the drug-coated stent. Drug-coated stents were virtually non-existent as recently as five years ago, but now they command more than 85 percent of the stent market. The FDA has scheduled meetings for this coming December in order to discuss the issue in more detail and perhaps call for further studies.
This week, an FDA official urged Boston Scientific and Johnson & Johnson, the two largest stent producers, to conduct further research into the matter. “The real question is how to expand the knowledge base for many thousands of patients being treated ‘off-label,’” said Bram Zuckerman, director of the FDA’s division for cardiac devices.
The debate over the use of stents has divided the medical community. Most agree that the use of stents–mesh tubes used to hold open clogged arteries–have been instrumental in saving thousands of lives. Beyond that, other questions remain: Are too many doctors recommending the stenting process rather than more traditional treatments such as medication or surgery? Are the more expensive drug-coated stents more dangerous than cheaper non-coated ones? Are the safety risks connected to the method and accuracy of implantation, rather than the product itself?
Several studies this year have pointed to long-term risks of clotting associated with the drug-coated stents in particular. The coated stents are used to prevent tissue from reforming in the arteries. What seems most alarming about them, according to recent studies, is that the risk of clotting has not diminished over time, forcing some patients to remain on anti-clotting medication for extended periods.
Last week, a New England Journal of Medicine study reported that the risk of stroke or death was more than two times higher for patients receiving stents than it was for patients who are treated by endarterectomy (an invasive surgical treatment). That study specifically regarded patients suffering from carotid artery blockage. In a commentary in the same issue of the NEJM, Dr. Anthony J. Furlan said, “The benefits of surgery in reducing the long-term risk of stroke need to be weighed against the immediate risk of death or stroke as a complication of the surgery.” He also said that, based on current FDA guidelines, stenting should be reserved for those patients with a significant (more than 70 percent) blockage who have displayed stroke symptoms and are at a high risk of surgical complications.
Recent evidence points to an increased risk of fatal blood clotting associated with a particular type of stent, the drug-coated stent. Drug-coated stents were virtually non-existent as recently as five years ago, but now they command more than 85 percent of the stent market. The FDA has scheduled meetings for this coming December in order to discuss the issue in more detail and perhaps call for further studies.
This week, an FDA official urged Boston Scientific and Johnson & Johnson, the two largest stent producers, to conduct further research into the matter. “The real question is how to expand the knowledge base for many thousands of patients being treated ‘off-label,’” said Bram Zuckerman, director of the FDA’s division for cardiac devices.
The debate over the use of stents has divided the medical community. Most agree that the use of stents–mesh tubes used to hold open clogged arteries–have been instrumental in saving thousands of lives. Beyond that, other questions remain: Are too many doctors recommending the stenting process rather than more traditional treatments such as medication or surgery? Are the more expensive drug-coated stents more dangerous than cheaper non-coated ones? Are the safety risks connected to the method and accuracy of implantation, rather than the product itself?
Several studies this year have pointed to long-term risks of clotting associated with the drug-coated stents in particular. The coated stents are used to prevent tissue from reforming in the arteries. What seems most alarming about them, according to recent studies, is that the risk of clotting has not diminished over time, forcing some patients to remain on anti-clotting medication for extended periods.
Last week, a New England Journal of Medicine study reported that the risk of stroke or death was more than two times higher for patients receiving stents than it was for patients who are treated by endarterectomy (an invasive surgical treatment). That study specifically regarded patients suffering from carotid artery blockage. In a commentary in the same issue of the NEJM, Dr. Anthony J. Furlan said, “The benefits of surgery in reducing the long-term risk of stroke need to be weighed against the immediate risk of death or stroke as a complication of the surgery.” He also said that, based on current FDA guidelines, stenting should be reserved for those patients with a significant (more than 70 percent) blockage who have displayed stroke symptoms and are at a high risk of surgical complications.
Defying Conventional Wisdom, Boston Scientific Admits Taxus Stent Causes Blood Clots but not Heart Attacks or Strokes
Safety concerns over drug-coated stents used for angioplasty procedures began are nothing new. Fear of blood clots and other complications associated with these stents began to surface shortly after the new devices came to market. However, two recent developments have doctors and patients contemplating if the devices should be used at all. Data presented at a recent European cardiology meeting has convinced some researchers that drug-coated stents do increase the risk of blood clots. And just yesterday, Boston Scientific admitted that their Taxus drug-coated stent increases the risk of blood clots, but denied these clots increased the risk of heart attack or stroke. Admitting that Taxus stents cause blood clots, but not heart attacks or strokes has left many medical professionals quite confused, since it is widely known that blood clots can cause both of these life threatening conditions.
Perhaps Boston Scientific is worried about what life would look like if drug-coated stents were no longer used. It is estimated that Boston Scientific and Johnson & Johnson generated over $5 billion in drug-coated stent sales last year alone. Losing a vital revenue stream could be devastating for Boston Scientific. Wall Street is still wary about the company’s acquisition of Guidant, who is facing numerous lawsuits from patients who received faulty defibrillators and pacemakers. Boston Scientific also faces new competition in the stent market from Abbott Laboratories, Medtronic and Conor Medsystems.
Johnson & Johnson brought the first drug-coated stent, Cypher, to market over three years ago. Drug-coated stents were introduced to combat restinosis, re-clogging of the arteries, that was common with plain metal stents. Restinosis often required the need for secondary angioplasty. Drug-coated stents, like Taxus and Cypher, use a drug and polymer coating to prevent Restinosis, making the need for secondary angioplasty less frequent.
Due to growing concern about blood clots, many doctors prescribe blood thinners for long periods of time after a drug-coated stent is used. However, the use of blood thinners also comes with risk. Plavix, a drug commonly prescribed to angioplasty patients, has been linked with serious ulcers. Other popular blood thinners, including Heparin and Lovenox, also come with a long list of potential side effects. The longer the blood thinners are prescribed, the greater the risk of experiencing their side effects.
Perhaps Boston Scientific is worried about what life would look like if drug-coated stents were no longer used. It is estimated that Boston Scientific and Johnson & Johnson generated over $5 billion in drug-coated stent sales last year alone. Losing a vital revenue stream could be devastating for Boston Scientific. Wall Street is still wary about the company’s acquisition of Guidant, who is facing numerous lawsuits from patients who received faulty defibrillators and pacemakers. Boston Scientific also faces new competition in the stent market from Abbott Laboratories, Medtronic and Conor Medsystems.
Johnson & Johnson brought the first drug-coated stent, Cypher, to market over three years ago. Drug-coated stents were introduced to combat restinosis, re-clogging of the arteries, that was common with plain metal stents. Restinosis often required the need for secondary angioplasty. Drug-coated stents, like Taxus and Cypher, use a drug and polymer coating to prevent Restinosis, making the need for secondary angioplasty less frequent.
Due to growing concern about blood clots, many doctors prescribe blood thinners for long periods of time after a drug-coated stent is used. However, the use of blood thinners also comes with risk. Plavix, a drug commonly prescribed to angioplasty patients, has been linked with serious ulcers. Other popular blood thinners, including Heparin and Lovenox, also come with a long list of potential side effects. The longer the blood thinners are prescribed, the greater the risk of experiencing their side effects.
Medicated stents are bad news
Drug-coated stents used to prop open blocked arteries may cause potentially fatal blood clots in rare cases, said experts at the World Cardiology Congress (WCC) in Barcelona. Safety concerns were raised when a Swiss-Dutch study presented at the WCC said recipients of drug-coated stents were at increased risk of potentially-fatal thrombosis (blood clots). The study tracked 8,146 patients. Two other Swiss studies also reported that drug-coated stents had higher risk of thrombosis compared to bare-metal stents that are not medicated.
Drug-coated stents are preferred over bare-metal stents by many interventionists because they bring down risk of artery re-blockage (restenosis) from about 25 per cent to less than 10 per cent. Drug-coated stents have been implanted in almost 60 lakh people worldwide since they were introduced in 2000, with about 1.5 lakh people using them in India since June 2002.
According to the Interventional Council of India, 60 per cent of the 65,000 stents implanted in India last year were drug-coated.
But now cardologists say the drug-coated therapy may be too aggressive. Bare metal stents allow a thin layer of cells to grow over them to make a biological lining. The medicines in the drug-coated ones, however, prevent tissue growth to could block the arteries from growing. While too much tissue growth is bad, a thin layer of cells is essential to cover the exposed metal, which if not covered can cause clotting and block arteries.
“When the polymer used to deliver the medicines in drug-coated stents is too aggressive, it remains on the stent for over six months to a year and continues to prevent cell-coating from forming. This increases risk of long-term clotting. New generation drug-coated stents are using less-aggressive bio-stable polymers to overcome this problem,” says Swaminathan Jayaraman, CEO of the Bangalore-based Vascular Concepts, the manufacturers of Pro-Nova.
While there has been a shift away from using drug-coated stents in the US, cardiologists in India say these devices cannot be ignored in India because they bring down risk of restenosis. “Since most Indians have diffused heart disease with multiple and longer blockages, and complications such as diabetes, they cannot undergo repeat procedures, so I’d still recommend drug-coated stents for the main arteries,” says Dr Purshotam Lal, director of interventional cardiology at Metro Heart Institute and a member of the health ministry’s expert committee set up to regulate cardiovascular devices (including stents) in India.
“The clotting risk usually occurs from six months to a year after implantation, but may remain for up to three years if the patient does not take blood-thinning medicines such as aspirin and clopidogrel. The patient has to continue taking both drugs for at least a year and longer if he has risk factors such as diabetes,” says Dr Ashok Seth, Chairman & Chief Cardiologist Max Devki Devi Heart and Vascular Institute.
This is not the first time the drug-coated stents have come under a shadow: In 2003, the US Food and Drug Administration issued a warning after receiving more than 290 reports of blood clots in Cypher patients, with more than 60 deaths associated to the device. The Taxus stent has been linked to a life-threatening mechanical defect that caused three deaths and severa complications, which has resulted in a recall of over 1 lakh of the medical devices.The FDA, however, did not ask for drug-covered stents to be withdrawn.
Drug-coated stents are preferred over bare-metal stents by many interventionists because they bring down risk of artery re-blockage (restenosis) from about 25 per cent to less than 10 per cent. Drug-coated stents have been implanted in almost 60 lakh people worldwide since they were introduced in 2000, with about 1.5 lakh people using them in India since June 2002.
According to the Interventional Council of India, 60 per cent of the 65,000 stents implanted in India last year were drug-coated.
But now cardologists say the drug-coated therapy may be too aggressive. Bare metal stents allow a thin layer of cells to grow over them to make a biological lining. The medicines in the drug-coated ones, however, prevent tissue growth to could block the arteries from growing. While too much tissue growth is bad, a thin layer of cells is essential to cover the exposed metal, which if not covered can cause clotting and block arteries.
“When the polymer used to deliver the medicines in drug-coated stents is too aggressive, it remains on the stent for over six months to a year and continues to prevent cell-coating from forming. This increases risk of long-term clotting. New generation drug-coated stents are using less-aggressive bio-stable polymers to overcome this problem,” says Swaminathan Jayaraman, CEO of the Bangalore-based Vascular Concepts, the manufacturers of Pro-Nova.
While there has been a shift away from using drug-coated stents in the US, cardiologists in India say these devices cannot be ignored in India because they bring down risk of restenosis. “Since most Indians have diffused heart disease with multiple and longer blockages, and complications such as diabetes, they cannot undergo repeat procedures, so I’d still recommend drug-coated stents for the main arteries,” says Dr Purshotam Lal, director of interventional cardiology at Metro Heart Institute and a member of the health ministry’s expert committee set up to regulate cardiovascular devices (including stents) in India.
“The clotting risk usually occurs from six months to a year after implantation, but may remain for up to three years if the patient does not take blood-thinning medicines such as aspirin and clopidogrel. The patient has to continue taking both drugs for at least a year and longer if he has risk factors such as diabetes,” says Dr Ashok Seth, Chairman & Chief Cardiologist Max Devki Devi Heart and Vascular Institute.
This is not the first time the drug-coated stents have come under a shadow: In 2003, the US Food and Drug Administration issued a warning after receiving more than 290 reports of blood clots in Cypher patients, with more than 60 deaths associated to the device. The Taxus stent has been linked to a life-threatening mechanical defect that caused three deaths and severa complications, which has resulted in a recall of over 1 lakh of the medical devices.The FDA, however, did not ask for drug-covered stents to be withdrawn.
Doctors warn of potential risk from drug coated stents
An editorial in a prominent online medical journal by two California doctors says drug-coated metal stents that are used to open heart arteries, pose a higher risk of life-threatening blood clots than older-generation stents without drug coating. They suggest that more than 2000 patients die each year from complications linked to the stents. Drug-coated stents are made in the U.S. by Boston Scientific and Johnson and Johnson. Boston Scientific manufactures its stents in the Twin Cities and employs 6,800 workers locally.
This is not the first claim regarding the potential dangers posed by drug-coated stents. At a scientific meeting in Barcelona in September, European investigators reported seeing a small but significant increase in the rate of death and heart attack among drug-coated stent recipients in long term follow-up trials. Similar findings were reported at a medical meeting in Atlanta in March.
Dr. Sanjay Kaul, a cardiologist at Cedars-Sinai Medical Center in Los Angeles and co-author of the recent editorial published on Cardiosource.com, examined both studies and several others published in the medical literature. He and co-author Dr. George Diamond found that an analysis of all the research so far suggests that drug-coated stents increase the risk of getting a clot by just over a half a percent when compared to patients with bare metal stents. Kaul and his colleague estimate the number of deaths associated with that higher risk could surpass 2000 patients a year in the U.S.
"If you do the math, if you assume a 45-percent case fatality rate and with 1 million interventions and you assume 80-percent of those are with drug-eluting stents, then it is possible that there may be an excess risk of death to the amount of 2160," he says.
Kaul is quick to point out, that number isn't based on actual deaths. He says a much larger study needs to be conducted to determine the real death rate and possible explanations for it. He speculates that one contributing factor has to do with the difference between real-world medicine and controlled clinical trials. Kaul thinks some patients have demanded the new technology. He says it appears physicians and hospitals have been too eager to give it to them.
"Perhaps we as physicians and patients got suckered in by the hype and now I think we are finding out that not all is hunky-dory with these devices and therefore we need to keep an open mind and be influenced and driven by the data. And if the data are telling us that there is some problems we need to recognize them and rectify them," he said.
Boston Scientific recently disclosed to the Food and Drug Administration that it too has found a slightly higher clotting risk on its Taxus drug-coated stent than its bare metal stents. But company spokesman Paul Donovan insists that discovery has not translated into increased deaths.
"We have observed a small increase in the rate of late-stent thrombosis also known more simply as blood-clotting. Our analysis of more than 3500 patients who received our drug-eluting stent has shown no clinically meaningful increase in heart attack or death when compared to bare metal stents," Donovan said.
Donovan wouldn't comment directly on Kaul and Diamond's editorial. But he did say he's confident the scrutiny will ultimately reveal the benefits of drug-coated stents far outweigh any risks.
"No therapy that has a benefit is without a risk and the risk here is very, very small."
Boston Scientific is the leader in the $6 billion a year stent market. The company develops and makes its stents in Maple Grove. Johnson & Johnson also markets a drug-coated stent.
The FDA says it will convene a panel before the end of the year to evaluate the studies presented in Atlanta and Barcelona. The agency says the data have raised important questions. But for now, the FDA believes the devices remain safe and effective.
This is not the first claim regarding the potential dangers posed by drug-coated stents. At a scientific meeting in Barcelona in September, European investigators reported seeing a small but significant increase in the rate of death and heart attack among drug-coated stent recipients in long term follow-up trials. Similar findings were reported at a medical meeting in Atlanta in March.
Dr. Sanjay Kaul, a cardiologist at Cedars-Sinai Medical Center in Los Angeles and co-author of the recent editorial published on Cardiosource.com, examined both studies and several others published in the medical literature. He and co-author Dr. George Diamond found that an analysis of all the research so far suggests that drug-coated stents increase the risk of getting a clot by just over a half a percent when compared to patients with bare metal stents. Kaul and his colleague estimate the number of deaths associated with that higher risk could surpass 2000 patients a year in the U.S.
"If you do the math, if you assume a 45-percent case fatality rate and with 1 million interventions and you assume 80-percent of those are with drug-eluting stents, then it is possible that there may be an excess risk of death to the amount of 2160," he says.
Kaul is quick to point out, that number isn't based on actual deaths. He says a much larger study needs to be conducted to determine the real death rate and possible explanations for it. He speculates that one contributing factor has to do with the difference between real-world medicine and controlled clinical trials. Kaul thinks some patients have demanded the new technology. He says it appears physicians and hospitals have been too eager to give it to them.
"Perhaps we as physicians and patients got suckered in by the hype and now I think we are finding out that not all is hunky-dory with these devices and therefore we need to keep an open mind and be influenced and driven by the data. And if the data are telling us that there is some problems we need to recognize them and rectify them," he said.
Boston Scientific recently disclosed to the Food and Drug Administration that it too has found a slightly higher clotting risk on its Taxus drug-coated stent than its bare metal stents. But company spokesman Paul Donovan insists that discovery has not translated into increased deaths.
"We have observed a small increase in the rate of late-stent thrombosis also known more simply as blood-clotting. Our analysis of more than 3500 patients who received our drug-eluting stent has shown no clinically meaningful increase in heart attack or death when compared to bare metal stents," Donovan said.
Donovan wouldn't comment directly on Kaul and Diamond's editorial. But he did say he's confident the scrutiny will ultimately reveal the benefits of drug-coated stents far outweigh any risks.
"No therapy that has a benefit is without a risk and the risk here is very, very small."
Boston Scientific is the leader in the $6 billion a year stent market. The company develops and makes its stents in Maple Grove. Johnson & Johnson also markets a drug-coated stent.
The FDA says it will convene a panel before the end of the year to evaluate the studies presented in Atlanta and Barcelona. The agency says the data have raised important questions. But for now, the FDA believes the devices remain safe and effective.
Doctors Debate the Merits of Drug-Coated Stents
The question isn't so much whether to use stents on heart patients, but which stent to use.
New evidence emerging at the annual meeting of the American Heart Association (AHA), in Chicago, suggests that drug-eluting stents may not be completely safe over the long term.
"This is a topic extremely important to the cardiology community," said Dr. Sidney Smith Jr., past president of the AHA and director of the Center for Cardiovascular Science and Medicine at the University of North Carolina at Chapel Hill. "We may not have a war on our hands, but certainly a very spirited discussion about where we stand, what we know and possibly what action we might need to take."
Smith moderated a news conference Monday that dealt with the issue of stents.
Narrowing of an artery -- called stenosis -- is commonly treated with balloon angioplasty and insertion of a stent, a wire mesh tube that props open the artery. Drug-eluting stents, first approved in 2003, slowly release drugs to prevent scarring and possible restenosis, or re-closing of the vessel.
Drug-eluting stents have quickly eclipsed bare metal stents, accounting for some 80 percent to 90 percent of placements, according to experts speaking at the news conference.
"We try to use stents whenever possible and drug-eluting stents whenever possible," said Dr. David Williams, senior author of one of the studies and professor of medicine at Brown University Medical School in Providence, R.I. "Some, however, have raised concerns that drug-eluting stents may be associated with an increased risk of stent thrombosis [blood clots] in follow-up and may lead to death and heart attacks."
"They are used in the majority of cases, but the long-term outcome in the real world is not known," echoed Dr. Joseph B. Muhlestein, professor of medicine at the University of Utah in Salt Lake City.
The bottom line? "Cardiologists are now faced with the decision of what type of stent to use," Williams said. "The issues are related to safety and efficacy and magnitude of prevention of recurrent procedures."
Williams' study compared patients treated with bare metal stents and with drug-eluting stents in a routine-practice population. Of more than 3,000 patients studied, one-year adverse event rates were similar, although bare metal stent patients were more likely to require follow-up revascularization or bypass surgery. In-hospital and one-year death rates were not statistically significantly different, Williams said. The success rate was similar in both groups -- about 98 percent.
"These data support the use of drug-eluting stents in routine clinical practice," Williams said.
Muhlestein's study, however, found that the all-cause death rate was higher in patients treated with drug-eluting stents than in those treated with bare metal stents after three years.
"Given the current dominance of drug-eluting stents in current practice, certainly we think these findings raise concern," Muhlestein said. "We need more long-term scrutiny."
Yet another study, this one conducted in the Netherlands, compared two different types of drug-eluting stents (sirolimus-eluting stents and paclitaxel-eluting stents) and found little difference in outcomes.
Experts on Monday debated the implications of the new evidence.
"I don't believe there is a difference in death or heart attack that's been demonstrated between drug-eluting stents and bare metal stents at this point," Williams said. "I would attempt to put in drug-eluting stents, although I do think there are technical instances where delivery of the bare metal stent is easier."
Muhlestein said: "To some degree, I agree, but our study unexpectedly found this increase in death, which led me to wonder whether maybe we're being too aggressive. Perhaps we ought to consider other alternatives for complex patients." He added that he would not stop using drug-eluting stents but would consider them more carefully.
Dr. John Kao, assistant professor of medicine at the University of Illinois, Chicago, and author of a study that found that privately insured patients were most likely to get drug-eluting stents, had this to say: "There is a cause for concern about the long-term safety profile of drug-eluting stents, but, right now, there's no definitive evidence suggesting that they are a cause of increased morality."
Much rests on the duration of anti-platelet therapy given after insertion of a stent. Guidelines issued earlier this year recommend anti-platelet therapy for up to six months, depending on the type of stent used, with use continuing up to one year also reasonable, Smith said.
Since then, however, "evidence has continued to gather that too many patients stop anti-platelet therapy before even completing a month, which puts them at significant risk," Smith said. "Then, a series of presentations at the World Cardiology Congress in Barcelona suggested that we might need to think even more seriously about the nature of anti-platelet therapy and its duration."
"Longer duration of anti-platelet therapy is probably going to turn out to be one of the factors," Kao agreed.
"It's concerning," said Dr. Nieca Goldberg, AHA spokeswoman and chief of women's cardiac care at Lenox Hill Hospital in New York City. "The question is, what's a doctor to do? And there's a lack of guidelines. We have to have a wider view of new technology."
New evidence emerging at the annual meeting of the American Heart Association (AHA), in Chicago, suggests that drug-eluting stents may not be completely safe over the long term.
"This is a topic extremely important to the cardiology community," said Dr. Sidney Smith Jr., past president of the AHA and director of the Center for Cardiovascular Science and Medicine at the University of North Carolina at Chapel Hill. "We may not have a war on our hands, but certainly a very spirited discussion about where we stand, what we know and possibly what action we might need to take."
Smith moderated a news conference Monday that dealt with the issue of stents.
Narrowing of an artery -- called stenosis -- is commonly treated with balloon angioplasty and insertion of a stent, a wire mesh tube that props open the artery. Drug-eluting stents, first approved in 2003, slowly release drugs to prevent scarring and possible restenosis, or re-closing of the vessel.
Drug-eluting stents have quickly eclipsed bare metal stents, accounting for some 80 percent to 90 percent of placements, according to experts speaking at the news conference.
"We try to use stents whenever possible and drug-eluting stents whenever possible," said Dr. David Williams, senior author of one of the studies and professor of medicine at Brown University Medical School in Providence, R.I. "Some, however, have raised concerns that drug-eluting stents may be associated with an increased risk of stent thrombosis [blood clots] in follow-up and may lead to death and heart attacks."
"They are used in the majority of cases, but the long-term outcome in the real world is not known," echoed Dr. Joseph B. Muhlestein, professor of medicine at the University of Utah in Salt Lake City.
The bottom line? "Cardiologists are now faced with the decision of what type of stent to use," Williams said. "The issues are related to safety and efficacy and magnitude of prevention of recurrent procedures."
Williams' study compared patients treated with bare metal stents and with drug-eluting stents in a routine-practice population. Of more than 3,000 patients studied, one-year adverse event rates were similar, although bare metal stent patients were more likely to require follow-up revascularization or bypass surgery. In-hospital and one-year death rates were not statistically significantly different, Williams said. The success rate was similar in both groups -- about 98 percent.
"These data support the use of drug-eluting stents in routine clinical practice," Williams said.
Muhlestein's study, however, found that the all-cause death rate was higher in patients treated with drug-eluting stents than in those treated with bare metal stents after three years.
"Given the current dominance of drug-eluting stents in current practice, certainly we think these findings raise concern," Muhlestein said. "We need more long-term scrutiny."
Yet another study, this one conducted in the Netherlands, compared two different types of drug-eluting stents (sirolimus-eluting stents and paclitaxel-eluting stents) and found little difference in outcomes.
Experts on Monday debated the implications of the new evidence.
"I don't believe there is a difference in death or heart attack that's been demonstrated between drug-eluting stents and bare metal stents at this point," Williams said. "I would attempt to put in drug-eluting stents, although I do think there are technical instances where delivery of the bare metal stent is easier."
Muhlestein said: "To some degree, I agree, but our study unexpectedly found this increase in death, which led me to wonder whether maybe we're being too aggressive. Perhaps we ought to consider other alternatives for complex patients." He added that he would not stop using drug-eluting stents but would consider them more carefully.
Dr. John Kao, assistant professor of medicine at the University of Illinois, Chicago, and author of a study that found that privately insured patients were most likely to get drug-eluting stents, had this to say: "There is a cause for concern about the long-term safety profile of drug-eluting stents, but, right now, there's no definitive evidence suggesting that they are a cause of increased morality."
Much rests on the duration of anti-platelet therapy given after insertion of a stent. Guidelines issued earlier this year recommend anti-platelet therapy for up to six months, depending on the type of stent used, with use continuing up to one year also reasonable, Smith said.
Since then, however, "evidence has continued to gather that too many patients stop anti-platelet therapy before even completing a month, which puts them at significant risk," Smith said. "Then, a series of presentations at the World Cardiology Congress in Barcelona suggested that we might need to think even more seriously about the nature of anti-platelet therapy and its duration."
"Longer duration of anti-platelet therapy is probably going to turn out to be one of the factors," Kao agreed.
"It's concerning," said Dr. Nieca Goldberg, AHA spokeswoman and chief of women's cardiac care at Lenox Hill Hospital in New York City. "The question is, what's a doctor to do? And there's a lack of guidelines. We have to have a wider view of new technology."
Drug-coated stents increase the risk of blood clots
Heart experts attending the World Congress of Cardiology have expressed their concerns over the long-term safety record of drug-coated stents.
It seems that studies presented at the conference in Barcelona this week have raised new concerns about the risks associated with the drug-coated stents.
The drug-coated heart stents, tiny metal-mesh tubes used to prop open coronary arteries, were introduced in 2000 as an improvement on bare-metal stents but experts say in some cases they may encourage potentially fatal blood clots.
They have raised their concern as almost 6 million people worldwide now have the drug-lined versions.
A study by researchers in Holland and Switzerland which monitored 8,146 patients, found that recipients of drug-coated stents had an increased risk of potentially fatal thrombosis, or blood clots.
Two other Swiss studies, which carried out an analysis of other studies on the issue also found that first-generation drug-coated stents had a greater link to thrombosis compared to bare metal stents during the first three years following stent implantation.
The drug coated stents are meant to keep the arteries open after they have been cleared of fatty deposits and are often credited with saving patients from future heart attacks or bypass surgery.
With the bare metal stents, heart tissue grows naturally to cover the stent, providing a natural biological lining but sometimes a thick growth of tissue develops which is undesirable.
The drugs on the new devices prevent too much tissue growth but sometimes they work so well that they have prevented a protective cell layer from growing, leaving exposed metal, which can act as a clot magnet.
The drug-coated stents are now used in most procedures in wealthy countries such as the United States and Switzerland, but some cardiologists say they will be more cautious about their use in future.
Dr. Steven Nissen, president of the American College of Cardiology and director of cardiology at the Cleveland Clinic says the information is explosive and of concern but he believes there is already a shift in the U.S. away from using drug-coated stents in favour of their uncoated predecessors.
Some medical experts have expressed concern that the financial implications of reducing the use of the profitable drug-coated stents are taking priority over improving patients' health.
Drug coated stents cost around three times more than bare metal ones and the market is thought to be worth more than $5 billion a year.
Dr. Christoph Kaiser of Basel's University Hospital, who first raised concern over the drug-coated stents in 2005, said new evidence from an 18-month patient follow-up program suggested they may be worthwhile in only one in three cases.
Dr. Salim Yusef, professor of medicine and director of cardiology at McMaster University, Hamilton, Canada says it is a terrible indictment that despite six million of these procedures having been done there is no long-term safety data on them.
The new findings however are not expected to dramatically alter the use of drug-coated stents in the immediate future.
It seems that studies presented at the conference in Barcelona this week have raised new concerns about the risks associated with the drug-coated stents.
The drug-coated heart stents, tiny metal-mesh tubes used to prop open coronary arteries, were introduced in 2000 as an improvement on bare-metal stents but experts say in some cases they may encourage potentially fatal blood clots.
They have raised their concern as almost 6 million people worldwide now have the drug-lined versions.
A study by researchers in Holland and Switzerland which monitored 8,146 patients, found that recipients of drug-coated stents had an increased risk of potentially fatal thrombosis, or blood clots.
Two other Swiss studies, which carried out an analysis of other studies on the issue also found that first-generation drug-coated stents had a greater link to thrombosis compared to bare metal stents during the first three years following stent implantation.
The drug coated stents are meant to keep the arteries open after they have been cleared of fatty deposits and are often credited with saving patients from future heart attacks or bypass surgery.
With the bare metal stents, heart tissue grows naturally to cover the stent, providing a natural biological lining but sometimes a thick growth of tissue develops which is undesirable.
The drugs on the new devices prevent too much tissue growth but sometimes they work so well that they have prevented a protective cell layer from growing, leaving exposed metal, which can act as a clot magnet.
The drug-coated stents are now used in most procedures in wealthy countries such as the United States and Switzerland, but some cardiologists say they will be more cautious about their use in future.
Dr. Steven Nissen, president of the American College of Cardiology and director of cardiology at the Cleveland Clinic says the information is explosive and of concern but he believes there is already a shift in the U.S. away from using drug-coated stents in favour of their uncoated predecessors.
Some medical experts have expressed concern that the financial implications of reducing the use of the profitable drug-coated stents are taking priority over improving patients' health.
Drug coated stents cost around three times more than bare metal ones and the market is thought to be worth more than $5 billion a year.
Dr. Christoph Kaiser of Basel's University Hospital, who first raised concern over the drug-coated stents in 2005, said new evidence from an 18-month patient follow-up program suggested they may be worthwhile in only one in three cases.
Dr. Salim Yusef, professor of medicine and director of cardiology at McMaster University, Hamilton, Canada says it is a terrible indictment that despite six million of these procedures having been done there is no long-term safety data on them.
The new findings however are not expected to dramatically alter the use of drug-coated stents in the immediate future.
Subscribe to:
Posts (Atom)