Yourlawyer.com (Boston Scientific Taxus Stent News)

Lawsuits Allege Medtronic, Other Firms Illegally Marketed Surgical Ablation Products

Thu, 16 Jul 2009 00:00:00 -0700

Medtronic Inc., St. Jude Medical Inc., AtriCure Inc. and Boston Scientific Corp. all allegedly paid kickbacks to doctors in order to convince them to use their surgical ablation products to treat the heart-rhythm defect called atrial fibrillation, according to lawsuits recently unsealed in Texas. According to The Wall Street Journal, the lawsuits were filed by former employees of the companies.

Allegations of kickbacks by medical device makers are nothing new. For example, in 2007 a New Jersey based federal probe found that some orthopedic device makers made lucrative payments to U.S. physicians between 2002 and 2006 as a way to encourage doctors to favor their products. Stryker Orthopedics cooperated with prosecutors and escaped a fine, but agreed to federal monitoring for 18 months. The other companies, Zimmer Holdings Inc., Depuy Orthopaedics Inc., Biomet Inc. and Smith & Nephew Inc. agreed to a $311 million settlement with the Justice Department and the U.S. Department of Health and Human Services.

The lawsuits detailed by The Wall Street Journal, which were filed in federal court in Houston, are related to an inquiry in Texas by the U.S. Justice Department that was previously disclosed by several of the companies in filings with the Securities and Exchange Commission. They were originally filed in 2007, the Journal said.

According to the Journal, the lawsuits allege that a "fraudulent marketing and inducement campaign" involving kickbacks to doctors and hospitals resulted in excessive charges to the Medicare insurance program. For example, several of the suits allege that Boston Scientific, Medtronic and AtriCure marketed surgical ablation equipment as a treatment for atrial fibrillation even though it was not approved by the Food and Drug Administration to treat that condition.

Those charges were made by a former Boston Scientific salesperson, who the Journal says, claimed to have been fired after complaining about the company's allegedly illegal practices.

All of the companies involved in the lawsuits told The Wall Street Journal that they were cooperating with the probe. Boston Scientific is no longer in the ablation business, the Journal said.

FDA Approves Boston Scientific Stent Despite Earlier Problems

Mon, 13 Oct 2008 00:00:00 -0700

Late last week, Boston Scientific Corporation announced that U.S. health regulators approved the next-generation version of its widely used Taxus drug-coated stent. Boston Scientifc plans to begin selling the stent in early November.

Meanwhile, in March, Boston Scientific received an approvable letter from the Food and Drug Administration (FDA) for the stent, the Taxus Liberte. Receiving an approvable letter indicates that certain conditions must be met before full FDA approval is granted. The company also received a corporate warning letter from the FDA in 2006.

Stents are tiny wire-mesh tubes used to prop open arteries after doctors clear them of blockages. Newer stents are drug-coated to help prevent blood vessels from reclogging. The Taxus Liberte Stent is already approved overseas, and is one of Boston Scientific’s best selling stents abroad; the Taxus Express is the top seller in the U.S. In considering approval of the Liberte, the FDA asked Boston Scientific to prove its anti-clogging performance in patients was “non-inferior” to the Taxus Express. Boston Scientific said structural design improvements over the original market-leading Taxus make the Liberte more flexible for easier insertion during angioplasty procedures.

Meanwhile, this summer, the Wall Street Journal reported that a study used by Boston Scientific, when pursuing U.S. approval for its Taxus Liberte stent, used a flawed equation favoring its stent. According to the Journal, had Boston Scientific used one of several other calculation methods, the Liberte clinical trial would have failed. According to the Journal, Boston Scientific used the Wald interval, long criticized by statisticians for exaggerating clinical trial results. Worse, when publishing results of the 2006 Liberte study, Boston Scientific neglected to disclose it employed the Wald interval.

The Atlas study compared Taxus Liberte to the Taxus Express. According to the findings touted by Boston Scientific, the Liberte’s anti-clogging performance in patients was “non-inferior” to the Taxus Express. According to the Journal, Boston Scientific said there was less than a five percent chance that its finding was wrong—a measure known as p-value. In April 2007, in the Journal of the American College of Cardiology, the company’s researchers for the first time specified the p-value: 4.87 percent. Scientists generally regard studies with p-values above five percent to be failures, and medical journals typically will not publish such results.

The Journal’s own analysis of the Liberte study using equations other than the Wald interval found that study’s p-value was about 5.1%—failing to rule out the possibility that patients getting the Liberte stent will have markedly more artery recloggings than those receiving the Express. The Journal also sited other problems with the Taxus Liberte study. For example, because the Liberte stent uses a design similar to its predecessor, the Express, the FDA allowed the company to conduct an easier test than would be required for a newer product and allowed Boston Scientific to omit a control group of patients newly implanted with the Express. Instead, Boston Scientific was allowed to compare the Liberte’s fresh results with data it had collected on Express patients years earlier. Boston Scientific also didn’t have to “blind” participants in the study. Patients and doctors were aware that the stent being implanted was the model on trial—a Liberte. That can lead to a placebo effect, according to the Journal article.

Surgery Deemed More Effective Than Boston Scientifics Taxus Stent

Tue, 02 Sep 2008 00:00:00 -0700

Doctors are now reporting that Boston Scientific Corporation’s Taxus stent did not fare as well as bypass surgery in improving medical outcomes for the sickest patients with a build-up of fatty deposits in their arteries. After one year, 12.1 percent of bypass patients had died, experienced a heart attack or stroke, or required repeat surgery versus the 17.8 percent of those patients who received a tube—known as a stent—to prop open a clogged artery. The announcement was made at the European Society of Cardiology meeting in Munich today; Patrick Serruys at Rotterdam’s Erasmus University led the cardiologist team.

Improved stent development prompted doctors to test whether stents are as good as surgery in replacing blocked arteries. Surgery is currently used in about four-fifths of the patients in the United States and in slightly less cases in Europe, the doctors said. Long-term, patients may need to consider surgery followed by a month of recuperation, they added. “Surgeons won't be out of work,” Douglas Weaver, the president of the American College of Cardiology said. Meanwhile, with the exception of repeat procedures, stents and surgery did equally well. “For the bad outcomes—death, heart attack or stroke—the procedures were equal,'' Eckart Fleck, a cardiologist at the German Heart Center in Berlin, said.

Boston Scientific—this country’s largest stent manufacturer—funded the study, which tracked patients with built-up plaque in blood vessels that feed the heart, including the one vessel that doctors commonly call the “widow-maker.” Apparently, a blockage to the widow-maker is especially problematic as this cuts off the supply to the heart, causing patients to suddenly die.

Of 3,075 patients studied, approximately 1,200 had no options between a stent implant or bypass surgery due to the severity of their condition. The 1,800 remaining patients either had a device implanted or underwent chest surgery. Patients were followed for a year. The doctors report that bypass surgery remains the best option because its effects can last for over 10 years, whereas Stent patients had to return for repeat procedures more than twice as often; 13.7 percent compared with 5.9 percent for the surgery group. The study won't change current practice, Timothy Gardner, a surgeon who is president of the American Heart Association, said. “Some patients just want to avoid surgery at any cost, and these results provide some comfort,'' Gardner said.

Boston Scientific has had multiple voluntary recalls of its drug-coated Taxus devices because of defects in the delivery system. About 200 Taxus stents were recalled in July 2004. After identifying further problems, the company recalled 85,000 additional Taxus stents—both drug coated and bare metal types—later that month. In August 2004, an additional 3,000 Taxus stents were recalled that had been manufacture red prior to these recalls. The catheter problems appear to have been caused when too much heat was applied during the laser welding stage in the manufacturing process, the company said.

Other, earlier studies have found no benefit over stent implantation and indicated that surgery and implantation offer similar outcomes.

Efficacy of heart stents called into question

Tue, 27 Mar 2007 00:00:00 -0700

A seven-year US study has called into question whether doctors are overusing heart stents, the blockbuster tiny wire mesh tubes used to prop open narrowing coronary arteries.

The results of the study, called Courage, added more uncertainty to a stent market that recently has been thrown into flux over questions of safety, appropriate usage and new competition.

This flux was also highlighted by a 7 per cent fall in the share price of Boston Scientific, a leading US stent maker, because new data showed a forthcoming stent by rival Abbott Laboratories could be better than its most important product, Taxus.

Debate has swirled among the medical community, regulators and device-makers, raising questions over the past year on whether medical devices have been used too soon and too aggressively.

Drug-coated stents, whose coating helps keep arteries from scarring and closing again, have been at the centre of that debate as one of the most widely used devices.

Medical devices are increasingly feeling scrutiny, akin to that seen with pharmaceuticals, from doctors and US regulators concerned with potential emerging questions about long-term safety.

In addition, as use of expensive devices has increased markedly, more scrutiny has fallen on the relative benefit of new medical devices. For instance, a recent Food and Drug Administration panel recommended against approval of a implantable heart data monitor by Medtronic, a US group, that could transmit patient data to a doctor via the internet.

The Courage study, presented on Monday at the annual American College of Cardiology meeting, looked at whether people receiving stents and drug therapy had fewer deaths or heart attacks than those with drug therapy alone.

Importantly, the study sought to find out if stents in patients with stable coronary artery disease whose life was not acutely threatened reduced risk of death and heart attacks because such a benefit "had not been shown".

The study said that, in 2004, more than 1m stents were implanted in the US and 85 per cent were done so in patients with stable disease.

The Courage study found "no significant differences" by using bare-metal stents as compared with drug therapy alone, in death, heart attacks or stroke. It did find that patients with stents had fewer chest pains.

Angioplasty no better than drugs, study says

Tue, 27 Mar 2007 00:00:00 -0700

A large and long-awaited study finds that angioplasty works no better than medication at preventing heart attacks or death, a finding that could slow the growth of one of medicine's most common cardiac interventions.

The research comes on the heels of a growing debate over whether some patients are getting unnecessary angioplasty, a procedure that involves using a tiny balloon and metal scaffolds called stents to prop open clogged arteries.

Angioplasty is recommended for those with fully blocked arteries or who have had a heart attack. But the new study, presented at the American College of Cardiology's annual meeting in New Orleans yesterday, should give doctors and their patients with partially obstructed arteries the confidence to put off angioplasty or to skip surgery altogether, according to the researchers.

"The results are very striking," said Dr. Steven Nissen , president of the American College of Cardiology, who was not involved in the study. "This is important for patients because it does now mean patients have choices. If your symptoms aren't so severe and aren't interfering with your lifestyle, you can afford to wait."

Half of the 2,300 patients studied underwent angioplasty and took heart drugs, and were told to make lifestyle changes, such as exercising, losing weight, and giving up smoking. The other half received only lifestyle counseling and medication, including drugs to lower cholesterol, relax blood vessels, slow heart rate, and prevent blood clots. Both groups fared equally well after an average of 4 1/2 years, according to the study, also published online yesterday in The New England Journal of Medicine.

Stent manufacturer Boston Scientific Corp. of Natick criticized the study yesterday as not breaking any new ground, and said stents improve quality of life for patients with clogged arteries. The authors said their research suggested that improvements in quality of life were not statistically significant over the course of the study.

The use of angioplasty to open clogged arteries has taken off since the mid-1990s, increasing from about 430,000 procedures in 1995 to nearly 1.3 million in 2004 , with many of the more recent surgeries being done proactively, rather than after a life-threatening event.

The popularity of angioplasty has spurred debate among cardiologists, some of whom think the procedure is overused.

Dr. William Boden of Buffalo General Hospital said he designed the new study to determine how much added benefit angioplasty provided for people with few symptoms and was surprised to discover that, statistically, there was none.

The good news for patients, he said in a news conference: "You are no more or less at risk of developing a heart attack or dying if you defer angioplasty until some time down the road."

Angioplasty did provide a better quality of life than drugs alone for patients experiencing angina, the discomfort or chest pain that occurs when the heart muscle is deprived of oxygen.

Nissen said that angioplasty remains the treatment of choice for patients with a fully blocked artery, and that campaigns are underway to make sure patients having heart attacks are taken to hospitals that can swiftly perform an angioplasty.

Nissen and others said they think the procedure is probably done more often than needed, though the study's authors said they did not want to speculate about the amount of overuse.

Dr. William Maisel, a cardiologist at Beth Israel Deaconess Medical Center, said the bottom line is that patients and doctors need to make sure they're using angioplasty for the right reasons.

"To place a stent to reduce the chances of a heart attack or to prevent someone from dying, those are not reasons to put in a stent," said Maisel, chairman of a federal panel that examined stent safety.

Boston doctors tend toward the conservative, so they probably use the procedure less often than doctors elsewhere, according to Dr. Frederic S. Resnic, director of the cardiac catheterization laboratory at Brigham and Women's Hospital. Roughly 30 percent of the Brigham patients who get angioplasty have heart disease but are not in immediate danger of having a heart attack, he said.

"We have always been very careful to have detailed discussions with our patients with stable coronary artery disease, to make sure that they are comfortable and understand that we are considering the procedure to relieve the symptoms of angina, and reduce the number and amount of medications needed," he said.

The team of researchers, which included several from Hartford Hospital and the VA Connecticut Healthcare System, said their study may offer fresh evidence that heart disease is more of a systemwide than a localized problem in the body.

Using a stent addresses just one problem spot, but fails to correct other potentially more dangerous fat deposits in the diseased arteries.

The study, known as COURAGE, was paid for by the US Department of Veterans Affairs and the Canadian Institutes of Health Research , as well as 11 pharmaceutical companies, including Pfizer Inc., the maker of the world's top-selling drug, the cholesterol-lowering pill Lipitor .

The researchers acknowledge that one significant limitation of their study was that 85 percent of the patients were men and only 14 percent were non white.

Boston Scientific, which makes drug-coated stents, was sharply critical of the study.

"The results of the COURAGE trial don't really tell us much we didn't already know about the relative benefits of stents over drug therapy in the treatment of cardiovascular disease," the company said in a statement. "Stents have improved the lives of millions of patients, as amply demonstrated by a broad range of clinical trials and real-world experiences, but their benefits are found in safe, durable, and minimally-invasive relief of angina, rather than in further improving the already good survival of stable angina patients on medical therapy."

The company also criticized the study for failing to include drug-coated stents, which were not on the market when the study began.

Boden said that because drug-coated stents have not been shown to improve lifespan, using them instead of bare-metal stents would not have changed the study's results.

Study: Heart Stents Often Not Worth the Risk or Cost

Tue, 27 Mar 2007 00:00:00 -0700

A highly anticipated new study has called into question the long-term effectiveness of stents in the treatment of stable coronary artery disease. Researchers have determined that the use of drug therapy (including blood-pressure and cholesterol drugs) is just as effective in preventing heart attacks or death when compared to a combination of drug therapy and stent implantation. The study results were shared this week at the American College of Cardiology’s (ACC) annual Scientific Session and will be published next month in the New England Journal of Medicine (NEJM).

The Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) study included 2,287 angina (acute chest pain due to poor blood flow) patients with at least a 70 percent artery blockage in the U.S. and Canada and assigned each patient into one of two study arms: percutaneous coronary interventions (PCI) and optimal medical therapy (OMT) together or OMT alone. Researchers, led by cardiologist Dr. William Boden of Buffalo General Hospital in New York, followed patients for two-and-a-half to seven years, and results of the study showed a similar rate of death, heart attack, or stroke. “As an initial management strategy in patients with stable coronary artery disease,” the authors concluded, “PCI did not reduce the risk of death, myocardial infarction, or other major cardiovascular events when added to optimal medical therapy.”

“Conventional wisdom would indicate that PCI and OMT together would be superior to OMT alone,” said Dr. Boden. “Indeed, that was our initial hypothesis. But results of the COURAGE trial demonstrate that two treatments are not always better than one. These findings, along with data from recent studies of more than 5,000 patients combined, show that PCI has no impact on reducing major cardiovascular events.”

The results of the COURAGE study may have a dramatic effect on the way doctors treat their heart patients. Stenting, especially when using drug-coated devices, is a costly procedure and comes with a variety of other medical dangers, including an increased risk of blood clotting that may lead to heart attacks or strokes. Although the COURAGE study utilized only bare-metal stents, previous studies have already found that the drug-coated stents offer little added benefit when compared to the older and cheaper bare-metal variety. (Bare-metal stents have been shown to be ineffective over time, as many bare-metal-stent patients suffer from re-clogging of their arteries.) In light of the new findings, researchers hope that doctors will more closely follow the established medical guidelines, which call for aggressive drug therapy as the first option.

“During the past 30 years,” the authors write, “the use of percutaneous coronary intervention (PCI) has become common in the initial management strategy for patients with stable coronary artery disease in North America, even though treatment guidelines advocate an initial approach with intensive medical therapy, a reduction of risk factors, and lifestyle intervention (known as optimal medical therapy). In 2004, more than 1 million coronary stent procedures were performed in the United States, and recent registry data indicate that approximately 85 percent of all PCI procedures are undertaken electively in patients with stable coronary artery disease.”

Although they agree that PCI procedures are valuable in patients with acute coronary symptoms, they contend that a “similar benefit has not been shown in patients with stable coronary artery disease.” While PCI does improve blood flow, reduce the onset of angina, and assist with breathing in the short term, the “long-term prognostic effect remains uncertain.”

In an accompanying editorial in the NEJM, Drs. Judith Hochman and Gabriel Steg wrote: “The COURAGE trial should lead to changes in the treatment of patients with stable coronary artery disease, with expected substantial health care savings. PCI has an established place in treating angina but is not superior to intensive medical therapy to prevent myocardial infarction and death in symptomatic or asymptomatic patients such as those in this study.”

The news was not good for Boston Scientific and Johnson & Johnson, the two biggest stent manufacturers in the $5 billion a year industry, since the large majority of current stent patients do not suffer from acute symptoms. In effect, the research shows that stents are being significantly overused, at great cost (and indeed, risk) to the patient.

Heart Stents No Better Than Treating Stable Heart Patients With Medication, Study Shows

Mon, 26 Mar 2007 00:00:00 -0700

The study of more than 2,000 patients found that those who underwent the expensive procedure, known as angioplasty, in non-emergency situations were no less likely to suffer a heart attack or die than those who only took aspirin and other medicines to thin their blood and lower blood pressure and cholesterol, along with adopting life style changes.

The study is the first large, well-designed comparison of angioplasty to non-surgical care for patients who are not actually having heart attack or in imminent danger of one. Patients routinely undergo the procedure to relieve chest pain and to reduce the risk of having or dying from a heart attack.

"The data are compelling," said William E. Boden of the University of Buffalo, whose findings were released Monday by The New England Journal of Medicine to coincide with a presentation at a meeting of the American College of Cardiology in New Orleans. "We do too many of these procedures."

Several experts said they expected the findings will prompt a major shift in how doctors treat thousands of patients suffering from heart disease -- the nation's leading cause of death.

"These findings are pretty explosive," said Steven Nissen, president of the American College of Cardiology. "I think this is going to shake things up pretty significantly."

The findings underscore the danger of rushing to adopt a procedure before careful studies have been conducted to fully determine its benefits, Boden and others said.

"There was just this intuitive belief that it would be beneficial," Boden said. "But no one had ever done a proper randomized trial to see whether it actually improved outcomes. In the meantime, a whole industry has been created around this."

The researchers and others stressed that angioplasty clearly benefits patients who are in the throes of a heart attack or are at very high risk for one. But the findings indicate that for a patient whose condition is stable, medical therapy is just as effective at reducing the major risks. Such patients constitute at least one-third of those undergoing the 1.2 million angioplasties performed each year, and perhaps as much as 85 percent.

Some cardiologists who specialize in the procedures, however, argued that the study did not focus on the sickest patients who are most likely to benefit and that the main purpose of angioplasty in many is to alleviate chest pain, not to prevent heart attacks.

"I don't think this is going to cause any huge paradigm shift," said Gregory J. Dehmer, president of the Society for Cardiovascular Angiography and Interventions. "This study was limited to a fairly select group of patients with very stable symptoms."

But Boden said the study did include patients with moderate to severe heart disease, and that many such patients undergo the procedure in the belief it will protect them against heart attacks.

In the procedure, doctors thread a tiny balloon into clogged arteries, inflate the balloon to clear the blockage and insert a stent, a tiny wire lattice strut that props the artery open. The procedures cost at least $40,000 and are considered safe, although they do carry some risks.

The findings come on the heels of questions about the safety of a new generation of stents coated with drugs to keep arteries from reclosing. Those concerns had already led doctors curtail their use of the newer devices, and the new findings are expected to have a similar effect on angioplasty overall.

"There was an over-exuberance," said William O'Neill, a prominent cardiologist at the University of Miami. "I think we're getting a mid-course correction."

The findings could also help fuel a resurgence of bypass surgery, which has become far less common with the rise of angioplasty.

"There was this sense that angioplasty would produce the same result as bypass surgery," Nissen said. "I think this will cause a tilt toward more patients with stable conditions choosing medical therapy and more people who have more severe disease getting bypass surgery, which both relieves symptoms and reduces the risk for heart attack and death."

The new study involved 2,287 patients at 50 centers in the United States and Canada who had chest pain or other symptoms because one or more major arteries supplying blood to the heart had clogged. Half the patients received only standard medical treatment involving medication and life style changes such as quitting smoking, eating better and exercising. The other half received the same treatment plus angioplasty.

After about five years, the number of patients who experienced a heart attack, were hospitalized or died because of their heart problems was virtually identical in the two groups, the researchers found.

"There was no significant difference," Boden said. "The data are clear."

Although about one-third of patients who initially got medical treatment only later turned to angioplasty, the findings show how much medical treatment of heart disease has improved, Boden said.

"The paradigm for the last 20 years for patients like this been, 'Mr. Jones, you need a procedure.' End of discussion," Boden said. "I hope this will make people realize that patients have more options. They can safely choose to try medical therapy first."

Although study patients receiving angioplasty were somewhat more likely to be free of chest pain, known as angina, even that benefit was marginal, Boden said. After nearly five years, 74 percent of those patients were free of chest pain, compared to 72 percent of those who had medical treatment alone.

"One of the unexpected findings is that it's amazing how remarkably good medical therapy was for relieving angina," Boden said.

Heart stent makers brace for new heart study

Mon, 26 Mar 2007 00:00:00 -0700

Wall Street analysts and many doctors expect another potential setback for makers of stents when results of a blockbuster study Tuesday will answer whether an artery-opening procedure plus drugs is better than medication alone for lower-risk heart patients with chest pain.

It's the first big study to directly compare angioplasty procedures with drug therapy alone as a way to prevent heart attacks and deaths in non-emergency cases.

If the research reaches the conclusion many analysts and doctors expect that angioplasty offers little or no lifesaving benefit over drugs for these patients the finding would be the latest dose of bad news for makers of stents. The tiny mesh scaffolds are used in most angioplasties to keep vessels open after blockages have been cleared.

After new-model drug-coated stents reached the market in 2003, the global stent market including older bare-metal stents grew from about $2 billion a year to about $6 billion in 2005.

Drug-coated stents have been implanted in more than 6 million people worldwide a modern record for fastest use of a new medical device.

But use has fallen since new evidence emerged that drug-coated stents carry a slightly higher risk of triggering blood clots months or years later. Many doctors have returned to using the older bare-metal stents or doing bypass surgery instead of angioplasty until more is known.

The drug-coated stent market shrank last year and is expected to erode at a faster rate this year, due in part to anticipation of the newest heart study.

"This market went from zero to 100 mph, and now it's braking," said Citigroup analyst Matthew Dodds, who forecasts an 8 percent decline in overall stent sales this year, and slower market erosion through 2011.

For drug-coated stent makers such as Natick, Mass.-based Boston Scientific Corp. and New Brunswick, N.J.-based Johnson & Johnson, the shift has been costly, since drug-coated models cost around $2,100 apiece compared with $850 for bare-metal versions introduced more than a decade ago.

A stent is typically inserted into a heart artery during angioplasty, a procedure in which a miniature balloon is guided through a vessel in the groin and then inflated to flatten a clog and restore blood flow to the heart.

The stent keeps the artery open, and drug-coated ones ooze medication to keep scar tissue from forming and the vessel from squeezing shut again.

Angioplasty, with a cost ranging from about $10,000 to $38,000, is the top treatment for people suffering heart attacks. But as many as 85 percent of angioplasties are non-emergency and done for people with less severe blockages that cause recurrent chest pain.

The big study to be reported on Tuesday compared angioplasty plus optimal heart medications aspirin, beta blockers, ACE inhibitors and statins to lower cholesterol to medications alone. Results are to be presented Tuesday at the American College of Cardiology's annual meeting in New Orleans.

Pointing to earlier smaller studies, industry analysts and doctors believe angioplasties will be on the losing end.

"There's absolutely no indication" the study will show angioplasty is superior, said Thom Gunderson, an industry analyst with Piper Jaffray.

Dr. John Lopez, a cardiologist at the University of Chicago Hospitals, noted that the new study followed only patients whose heart conditions were stable, rather than those facing imminent risks. He believes that it's primarily higher-risk patients who benefit more from the artery-opening procedure.

"I'd be very surprised if there was a reduction in mortality," said Dr. William Maisel, a cardiologist at Beth Israel Deaconess Medical Center in Boston. "I suspect the bottom line we will be left with is that both options (angioplasty versus drugs only) are reasonable."

That result would mirror findings in recent studies including two within the past month that examined smaller groups.

If patients can't expect a better chance of long-term survival, angioplasty's cost may loom larger when it's elective, said Dr. David Cohen of St. Luke's Mid America Heart Institute in Kansas City, Mo.

Cohen said patients with stable heart problems, like the ones in the latest study, "probably should not be receiving this therapy (angioplasty) on a first-line basis."

Dr. Donald Baim, Boston Scientific's chief medical officer, said doctors should look beyond survival rates and consider whether angioplasty with stents relieves chest pain.

"The decision should be driven by the desire to limit chest pain with the least invasive alternative that's practical," Baim said.

Drug-coated stents accounted for about 89 percent of all stents implanted early last year, according to a study by Millennium Research Group, a Toronto-based firm that surveys doctors.

But that proportion fell to just 70 percent in February after more doctors opted for bare-metal versions because of the blood-clot fears from the drug-coated models.

Boston Scientific's drug-coated Taxus stent accounted for about 25 percent of the company's $2.1 billion in fourth-quarter sales down from 40 percent before the company bought Guidant Corp. for $27 billion last spring to diversify a medical devices portfolio overly dependent on Taxus.

In comparison, J&J is a far bigger company with revenue of $13.7 billion last quarter and far less dependent on its drug-coated Cypher stent, which nevertheless has been a key driver of J&J's profits in recent years.

In addition to hurting Boston Scientific and Johnson & Johnson, the shift away from drug-coated stents could also hit companies with next-generation drug-coated models that are just hitting European markets and are soon expected to arrive in the U.S. Such companies include North Chicago, Ill.-based Abbott Laboratories Inc., and Minnesota-based Medtronic Inc. and St. Jude Medical Inc.

Piper Jaffray's Gunderson foresees further damage if Tuesday's research results are as expected.

"No matter how well anticipated these results are, and no matter how the stock prices have adjusted to factor in the results we're all anticipating, there is still that impact from the headlines in the morning," he said.

Analysis: Stents' heart value in doubt

Mon, 26 Mar 2007 00:00:00 -0700

Doctors said Monday that angioplasty plus stenting a common, expensive heart procedure plus the best medical treatment failed to reduce the risk of death or heart attacks, when compared to optimal medical treatment alone.

In the blockbuster COURAGE Trial, doctors at the 56th annual scientific sessions of the American College of Cardiology said that the $38,000 angioplasty-plus-stent heart surgery now done a million times a year in the United States with the goal of freeing patients from chest pain did not, in the long run, even result in less pain.

"There are hundreds of thousands of Americans who are currently getting stents placed who do not need it as initial therapy," Dr. Raymond Gibbons, professor of medicine at the Mayo Medical School in Rochester, Minn., and president of the American Heart Association, told United Press International.

Thomas Ryan, senior consultant and emeritus chief of cardiology at Boston University, agreed.

"This study shows that, if you treat people vigorously and coach them and they get their blood pressure under control, patients can do just as well on medical therapy," he told UPI. But, he cautioned, "They can't just take a pill. This is hard work. They have to get out and exercise. They have to get maximum doses of lipid lowering drugs," he said.

Originally scheduled for simultaneous release at the ACC meeting and in the New England Journal of Medicine on Tuesday, the organizations reported the findings Monday after major portions of the report were leaked and were published online in various publications.

"Our findings parallel those reported in recent trials," said William Boden, chief of cardiology at Buffalo General and Millard Fillmore Hospitals. "In the aggregate, these studies, including our own, include outcome data on more than 5,000 patients and show that percutaneous coronary intervention angioplasty plus stenting has no effect in reducing major cardiovascular events."

Mayo's Gibbons said that the procedure does relieve pain in patients with angina, or chest pain, and still is the treatment of choice in people who have uncontrolled angina, a condition marked by pain even when at rest that is not well-controlled by use of drugs such as nitroglycerine.

Angioplasty with stent implantation is also recommended to open up coronary arteries in people in the throes of an acute heart attack. Such procedures can be lifesaving in these patients, he said.

In the COURAGE study, Boden, also professor of medicine and public health at the University at Buffalo School of Medicine and Biomedical Sciences, and colleagues across the United States and Canada recruited 2,287 patients who had evidence of heart disease.

Between 1999 and 2004, the researchers randomly assigned 1,149 patients to undergo angioplasty-plus-stent and to receive optimal medical therapy and 1,138 to receive optimal medical therapy alone.

The primary outcome of the study was the composite of death from any cause and nonfatal heart attacks. There were 211 such cases in the patients who received angioplasty and 202 patients in the medical-therapy-only patients. After about 4.6 years, about 19 percent of the patients who received angioplasty as an initial treatment experienced that primary outcome, compared with 18.5 percent of the medical treatment group a difference that did not reach statistical significance.

Similarly, regarding rates of heart attack, stroke or death the trial's secondary endpoint patients who got drugs and stents experienced these events at a rate of 20 percent, versus 19.5 percent in the drugs-alone group.

Boden, speaking at a press briefing Monday, said that one of the surprising findings of the study was that by five years, there was little difference between the groups among patients who were angina-free 74 percent of those having angioplasty and 72 percent of those following medical therapy.

"We set this study up with a hypothesis that angioplasty plus medical treatment would prove superior than just medical therapy alone," he said. "We wanted to give stenting the best chance to prove it had more benefits."

In angioplasty, doctors make a small incision in a patient's leg, allowing access to the main artery in the leg. Into that artery a balloon-tipped catheter is inserted. Using X-ray guidance, the catheter is advanced through the arterial system until it reaches the coronary arteries. When these arteries become blocked they can cause chest pain or heart attacks. The catheter is positioned at the point of coronary artery blockage and the balloon is inflated, crushing the blockage against the walls of the artery and opening the blood vessel.

To make sure blood keeps flowing, doctors then implant tiny mesh coils known as stents to act as scaffolding that props open the blood vessel.

Despite Monday's news, doctors were quick to note that stents still have a place in cardiac care.

"We shouldn't lose sight of the fact that revascularization angioplasty can be beneficial in acute situations," said Sidney Smith, professor of medicine at the University of North Carolina. "However, the foundation for all our work should be comprehensive medical therapy. If you get patients to take their medicine and treat to prescribed levels, patients can have benefits."

Jim Dove of Springfield, Ill., president-elect of the ACC, promised that the organization will consider sanctions against those individuals who were responsible for breaking the embargo on release of the study.

Steve Nissen, director of cardiovascular medicine at the Cleveland Clinic, and current ACC president, told UPI, "We are discussing sanctions. We will do what we think is right, but we will not do it rashly. We consider the embargo process an important part of the integrity of our studies."

House to scrutinize marketing of stents

Tue, 06 Mar 2007 00:00:00 -0800

As part of a federal inquiry into drug and medical-device marketing, Boston Scientific Corp. was asked by Congress last week to submit to investigators internal documents, marketing plans, and clinical data related to its top-selling product, the Taxus drug-coated stent.

In a letter sent to Boston Scientific chief executive Jim Tobin , Representative Henry Waxman , chairman of the chief investigative committee of the House of Representatives, requested information about whether the Natick company's marketing department funded any clinical studies on Taxus stents, whether it paid any of the studies' authors or doctors, and whether it withheld the results of any Taxus studies.

Waxman , a California Democrat, sent an identical letter to Cordis Corp. , the division of Johnson & Johnson that makes the only competing drug-coated stent in the United States. The letters cited "concerns about the safety and off-label use" of the stents, which were the subject of a two-day Food and Drug Administration hearing in December.

Both companies issued statements saying they planned to cooperate with Waxman's request.

Since their introduction in 2003, drug-coated coronary stents have become the fastest-selling medical device in history, bringing in about $5 billion a year for Boston Scientific and Johnson & Johnson, which is based in New Jersey. The tiny wire-mesh tubes are implanted to hold open cleared heart arteries.

The companies used powerful marketing campaigns to launch their products for use instead of an older generation of bare-metal stents. Recent data shows that while drug-coated stents can decrease the rate at which patients need to return for new heart procedures, they also slightly raise the risk of long-term clotting over the older, cheaper stents.

Waxman's letter cited the December FDA hearing, at which a panel of experts combed through a wide array of data on the benefits and risks of drug-coated stents. The panelists concluded that stents were safe and effective when used on the subset of heart patients for which they were initially approved, but they raised a flag of caution over the large number of patients who receive drug-coated stents despite falling outside those guidelines.

The letter came from the House Committee on Oversight and Government Reform, which Waxman chairs.

His request focuses on how the companies marketed their stents, asking for records of sales-training, presentations to doctors, and "all internal or external presentations or reports relating to off-label use." It also asks for a record of their funding of cardiology societies and events.

Stent research alarms patients

Mon, 26 Feb 2007 00:00:00 -0800

John Wehr couldn't believe what was he was reading. An article on drug-coated stents, the kind used to prop open his two clogged coronary arteries last June, said the devices have a ''small but significantly increased risk'' of life-threatening side-effects.

Worried, the 78-year-old retired Bethlehem Steel Corp. accountant clipped the article and called his cardiologist. He wasn't alone.

Drug-coated stents tiny mesh tubes coated in chemotherapy drugs have been considered the best medicine had to offer, superior to the uncoated variety in their ability to keep scar tissue at bay and prevent coronary arteries from reclosing.

They've been inserted in 6 million heart patients nationwide, including 5,000 in the Lehigh Valley.

But heart specialists have been forced to reconsider their use since December, when new research showed they are more likely to cause blood clots than do the bare-metal variety and the clots can appear six months to years after the stents are placed.

Clotting is a natural reaction to injury, but studies conducted in the United States and Sweden found that blood clots were getting stuck inside the stents, cutting off blood flow and causing heart attacks and sudden death. Researchers put the risk of developing clots at about 1 in 200-500 people.

Area cardiologists said they've found blood clots in the drug-coated stents of patients who survived heart attacks. And they can only presume that some others have died from the complication as well. Without autopsies, they can't know for sure.

Rapid escalation of use of the devices has only added to the alarm. Since they went on the market four years ago, drug-coated stents have far surpassed bare metal, becoming the stent of choice in 80-90 percent of all cases.

''It's a huge amount,'' local cardiologist Bryan Kluck acknowledged. At Lehigh Valley Hospital-Cedar Crest, where Kluck practices, cardiologists inserted the devices in about 1,700 patients last year. Over the same time at St. Luke's Hospital-Fountain Hill, about 1,000 patients received one or more drug-coated stents. Another 500 or so received the devices at Easton Hospital in Wilson.

In response to the findings, the American Heart Association, American College of Cardiology and other medical groups in early January recommended that most patients with drug-coated stents remain on anti-clotting medicines, such as the prescription drug Plavix, and aspirin, for at least a year, possibly indefinitely.

Experts believe continued use of anti-clotting medicines is the best recourse because research shows that patients who stayed on the drugs for a year fared the best among those studied. The 3-5 percent increased risk of blood clots occurred primarily among patients who stopped taking the medicines after six months.

Patients were supposed to stay on the pills for one to six months, depending on the type of stent used. However, one study showed the average time patients took the blood-thinners was 45 days.

''The increased risk [of blood clots] is very small and likely to be overcome if patients stay on anti-clotting medicines,'' noted Dr. Deepak Bhatt, a cardiologist and researcher at the Cleveland Clinic, which analyzed 14 studies involving drug-coated stents.

Promising, but not perfect

Two brands of drug-coated stents are used in the United States: Taxus by Boston Scientific Corp. and Cypher by Johnson & Johnson's Cordis Corp.

Placed inside a blocked coronary artery on the end of a deflated balloon, the stents are locked in place when the balloon is inflated. They act as a buttress to keep fatty deposits pinned against the artery wall. They restore blood flow to patients in the throes of a heart attack or who have blockages.

When they first came on the market, the drug-coated stents were recommended only for patients at low risk, such as those with small blockages in single vessels. But because early results with such patients looked so good, doctors used them in more common and complicated cases and in sicker patients.

Doctors had hints of a clotting problem from earlier studies, but it wasn't until the release of more conclusive data in December, much of it produced by the Duke Clinical Research Institute in Durham, N.C., that concern reached a critical level.

A rare summit of international experts called days later by the U.S. Food and Drug Administration produced the recommendation that patients remain on anti-clotting medication for a year or more.

But Dr. Robert A. Harrington, a professor of medicine in the division of cardiology and director of Duke's Clinical Research Institute, said the recommendation puts doctors and patients in another predicament.

''Are we committing millions of patients to lifelong [anti-clotting medicine] with its attendant costs and risks?'' he asks in an editorial about the blood-clot problems in a December issue of the Journal of the American College of Cardiology.

Plavix generic name clopidogrel and other blood-thinners can cause life-threatening internal bleeding in some patients, such as those with ulcers. It also has been shown to be no better than low-cost aspirin at preventing a first heart attack.

The Cleveland Clinic's Bhatt, however, doesn't think the side-effects of blood thinners are reason enough not to continue using drug-coated stents.

''Everything has risks,'' he said.

Weighing the risks

Some patients were so upset by the research that they asked that the stents be removed something doctors generally don't do, considering it much riskier than leaving the mesh tubes in place.

Cardiologists hope they can quickly learn which patients, beyond the low-risk, are best suited to drug-coated stents from patient registries and continued research. Or that the next generation of stents won't cause blood clots. In the works are stents with different coatings and others made to dissolve over time.

Until they have more answers, local and national specialists are extending the use of anti-clotting medicine. They also are being more selective in using drug-coated stents, perhaps precluding patients with long blockages or blockages that extend beyond one artery, persons with diabetes, persons scheduled for lung or colon cancer surgery or persons who have trouble keeping up pill regimens.

''There was a time that I'd try any case I could to use drug-coated stents,'' said Dr. Gary Costacurta, chief of cardiology at Easton Hospital in Wilson.

Now, Costacurta said, he may use bare-metal stents for patients with long blockages or for patients with blood vessels that are large in diameter.

LVH's Kluck said being more selective may not be so easy especially in the emergency room.

About 20 percent of the patients who receive stents arrive in the ER with chest pains and signs of imminent danger to the heart. It's a scenario in which seconds can make a difference, he said, in how much damage occurs to the heart and whether or not the patient lives.

Such cases leave little time for a full patient history, Kluck said. What medicines the patient had been taking or stopped taking and whether they have had bleeding problems in the past might not be known. ''It's not clear if plain stents are better than drug-coated'' for such patients, he said. ''We must probe deeper to know.''

Dr. Peter Puleo, a cardiologist and medical director of the catheterization laboratory at St. Luke's Hospital in Fountain Hill, said he started telling his patients to stay on anti-clotting medicines for two years when he read early studies suggesting a problem.

Puleo said he uses bare-metal stents on patients with long blockages or larger blood vessels. He said he is less worried about patients bleeding from blood-thinners than he is about heart attack and death from blood clots. ''Death from internal bleeding is even more unusual than late-term thrombosis,'' Puleo said, using another term for blood clots. ''In cardiology, more people clot than bleed to death.''

''It makes people nervous about continuing [on the medicines], but you can get through it,'' Puleo said.

Dr. J. Patrick Kleaveland, medical director of the catheterization laboratory at LVH and co-director of the lab at Grand View Hospital in West Rockhill Township, Bucks County, said drug-coated stents are still safe and effective in reducing restenosis for patients with simple, straight-forward blockages.

Patients at higher risk may still benefit as well, Kleaveland said, if they can stay on anti-clotting medicines for at least a year without uncontrolled bleeding. ''The patients I've seen with the most devastating problems are those who stopped taking their medicines prematurely,'' he said.

Reasons patients stop taking anti-clotting medication range from not being able to afford the pills, which cost $3-$4 a piece, to not feeling well on them or having difficulty keeping up with the regimen.

But cardiologists warn that stopping, even for a few days, could prove fatal if the body throws blood clots at the braced vessels.

''The first sign of trouble could be the total blockage of a stent, artery and blood flow,'' Kluck said. In other words, a sudden, massive heart attack.

Lehigh County Judge Edward Reibman stopped taking his prescription blood-thinner months after receiving a drug-coated stent in 2005. He counts himself lucky he didn't develop blood clots.

''When I had the stent put in, I was prescribed Plavix and aspirin, but I felt lousy on them,'' Reibman said, remembering muscle and bone pain.

He stopped the Plavix, switched to another anti-clotting drug and after a few months stopped that, too. But he continued taking a baby aspirin a day.

At a checkup in December, when news broke of the risk of blood clots, Reibman's doctor told him to resume the Plavix.

The judge wonders what new risks will come with the prescription medicine, but said he isn't judging prior decisions.

''Everyone thought the stents were fine. No one knew about this late stent [blood-clotting] problem then,'' he said. ''You make decisions with the best information you have at the time, and as science develops, you learn more and hopefully make more decisions.''

What's Up With Stents, Docs?

Mon, 12 Feb 2007 00:00:00 -0800

It's not often that the New England Journal of Medicine devotes most of its editorial content to a single subject—and releases the information early online. That's exactly what it did Monday with a series of five studies and several commentaries on drug-eluting coronary stents. As the editors explained, "Our motivation is the recent concern that the implantation of drug-eluting stents, as compared with bare-metal stents, may be associated with a small increased risk of late stent thrombosis, a potentially fatal complication."

Drug-eluting stents were hailed as a "breakthrough technology" in 2003 and 2004, when the FDA approved the Cypher and Taxus stents, respectively. Like the bare-metal stents that preceded them, these tiny wire-mesh scaffolds were designed to prop open narrowed blood vessels (a problem known as stenosis), reducing the chest pain known as angina. Unlike bare-metal stents, however, the Cypher and Taxus devices were coated with drugs, the purpose of which was to prevent arterial cells from multiplying rapidly and narrowing the blood vessels again, a process known as "restenosis."

Drug-eluting stents caught on rapidly. By the end of 2004, they were used in 80-90 percent of stenting procedures. (Several million have now been implanted worldwide.) But concerns about their safety began to surface in the fall of 2005 and came to a head in March 2006, when a large population study in Sweden suggested that, between 7 and 18 months after implantation, patients with drug-eluting stents had higher rates of so-called stent thrombosis, in which a blood clot forms on exposed metalheart attacks an event often associated with acute heart attacks and sudden death. (An animation illustrating both restenosis and stent thrombosis is available at www.nejm.org.) These concerns prompted the FDA to convene a panel of experts in December to sift through the available evidence.

The new studies give more detailed versions of the evidence presented at the FDA in December. Unfortunately, a clear conclusion is still not readily available. "You could write whatever headline you wanted," says Dr. William Maisel of Beth Israel Deaconess Medical Center in Boston, who chaired the FDA panel and wrote one of the overview papers in the journal. "You could write that drug-eluting stents and bare-metal stents are equally safe [the conclusion of a study headed by Christian Spaulding in France]. Or you could write that there was more stent thrombosis after a year with drug-eluting stents, but no significant differences in overall rates of death and heart attack at four years [the conclusion of another paper by Gregg Stone at Columbia University]." Or, frankly, you could write that there was not only more stent thrombosis after six months with drug-eluting stents, but also death rates 18 to 32 percent higher three years afterwards, as indicated in the Swedish study.

How could the papers reach such different conclusions? The formal studies that led to FDA approval longer, follow-up versions of which constitute four of the five studies in the New England Journal enrolled only patients with the simplest, least complicated cases of arterial stenosis. When the FDA granted approval for drug-eluting stents, it was for use in patients like these. But once the devices were approved, doctors started using them in patients with more complex problems, too, such as longer lesions and problems in multiple vessels. The Swedish registry included these "real-world" patients, not just the ideal candidates in the approval trials.

What's a prospective patient to do? If you're thinking about getting a stent, here are three points to consider:

First, almost everyone seems to agree that drug-eluting stents lead to a slightly greater risk of stent thrombosis six months or more after implantation of the device. That's not surprising. Because the arterial lining doesn't grow back as quickly as with bare-metal stents, the metal mesh is exposed for longer, presenting a rough surface on which clots can form. Even Dr. Donald Baim, chief medical and scientific officer of Boston Scientific, which makes the Taxus stent, agreed with the point in an audio interview posted on the New England Journal's Web site. To compensate for the increased risk, the FDA panel recommended that patients stay on blood-thinning agents like aspirin and Plavix for at least 12 months afterwards an increase from the previous recommendation of 3-6 months. In addition, recipients should not undergo elective surgery during that time.

Second, it's important to realize that stents are mainly effective for relief of angina. There's very little evidence that they prevent heart attacks or reduce deaths, except when implanted during a heart attack. That's because most heart attacks don't come from narrowed arteries, but from ruptured plaque, around which massive clots form. So if you suffer from angina and want an improved quality of life, stents are very likely to help. If it's a heart attack you're trying to prevent, then it's not clear how great the benefit may be. (In the long run, some doctors suggest that a better option for preventing heart attacks may be aggressive drug therapy for high cholesterol and blood pressure. It's logical that drugs might help more, since they affect the entire cardiovascular system, not just a single artery. We'll know better next month, when a large trial comparing stents-plus-drugs against drug therapy alone will be unveiled at the American College of Cardiology meeting.)

Third, says Maisel, despite the uncertainties, drug-eluting stents have been an important advance in the management of coronary artery disease. They clearly reduce the occurrence of restenosis and hence the need for repeat procedures. Patients with simple obstructions in coronary arteries the patients for whom the devices were approved will likely do well with them. "But there's no free lunch," he warns. Anti-clotting therapy is important. For patients with more complicated cases, the equation is still uncertain.

Making Sense of Drug-Coated Stents

Mon, 01 Jan 2007 00:00:00 -0800

When the FDA approved the use of drug-coated stents on April 24, 2003, it was hailed as a landmark advance in the treatment of blocked arteries.

“Drug-coated stents will be the new standard of cardiovascular care essentially immediately upon their release,” Dr. Campbell Rogers, director of the Cardiac Catheterization Laboratory at Brigham and Women’s Hospital (BWH), said at the time. House and Human Services Secretary Tommy Thompson called the decision “a significant step forward in the treatment of heart disease” while Mark McClellan, FDA Commissioner during that period, added that “drug-eluting stents combine drugs with medical devices to provide more effective care for many patients with heart disease. FDA is working to make sure its regulatory procedures encourage the quick and efficient approval of such safe and effective combination products.”

Significantly, the FDA’s announcement also made the following claim: “The types of adverse events seen with the drug-eluting stent were similar to those that occurred with the uncoated stent.” However, only three and a half years later, that statement is being challenged by a growing number of medical professionals, researchers, and consumer watchdogs who fear that the drug-coated device brings with it a higher risk of blood clots that can lead to heart attacks and strokes. Today, the questionable safety of drug-coated stents threatens to shake up this multibillion-dollar industry, raising a myriad of medical and legal issues.

On December 7 and 8, the FDA held a public Circulatory System Devices Advisory Panel meeting to discuss the issue and delivered the kind of mixed message that is typical at the FDA: Drug-coated stents were deemed safe for a certain subset of the patient population, but were also associated with a higher risk of blood clots, heart attacks, and death in the majority of patients. The panel recommended that the FDA issue new warnings for doctors and patients to reflect the elevated risk. The panel also sought to reduce instances of “off-label” usage, which accounts for more than half of the drug-coated stent market. Yet they saw no compelling reason to pull the controversial devices off the market.

In the long run, however, this may not be good news for stent makers. “Increased incidents of injury and adverse events are always important factors to examine when assessing the liability case against the manufacturers of drugs or medical devices,” says Jason Mark, an attorney at Parker & Waichman LLP who runs the firm’s mass tort unit. “With safer alternative designs available to patients that pose less thrombotic risk, manufacturers who place these products into the stream of commerce do so at their own peril and, unfortunately, at the peril of unsuspecting patients.”

In 2003, the news was all good for Cordis Corporation, the division of Johnson & Johnson that developed the drug-eluting stent (DES). At the time, the only stents in use were bare-metal stents (BMS). These devices–a kind of wire-mesh scaffolding–were used to prop open clogged arteries after angioplasty and had met with much success. However, according to the FDA, roughly 15 to 30 percent of stent patients suffered from restenosis (re-clogging of the artery) within a year of the procedure and had to be treated again with another angioplasty or bypass surgery.

The drug-eluting stent was developed to solve the problem of restenosis. By releasing a drug to retard cell growth and stop scar tissue from forming within arteries that have been opened, the new device was designed to prevent the arteries from becoming blocked again. Cordis had funded a national clinical trial to test the device’s effectiveness, and it was lauded as highly successful. The combined occurrence of repeat angioplasty, bypass surgery, heart attacks, and death was 8.8 percent for drug-eluting stent patients and 21 percent for the uncoated stent patients. The FDA said the new device was found to “significantly reduce the rate of re-blockage that occurs with existing stents.” BWH’s Dr. Rogers, who had been involved in the New England-based part of the trial, noted, “When we tested the drug-coated devices versus the plain metal version on patients, the results were very compelling. In approximately 95 percent of patients receiving the drug-coated stents, restenosis was prevented.”

Patients and medical professionals were so excited about the drug-coated stent that angioplasty procedures were being delayed specifically to await the FDA’s approval of the Cypher, Cordis’ revolutionary Sirolimus-Eluting Coronary Stent. The FDA issued its blessing in April of 2003, and by June, the device was already in short supply as demand soared. Patients had heard the news about drug-eluting stents, and suddenly, nobody wanted a bare-metal stent anymore.

It didn’t take long for the mood to change. In early July of 2003, less than three months after it approved the Cypher stent, the FDA issued its first warning about the product. In a July 8 alert, the agency stated: “Since the product’s introduction it is estimated that over 50,000 patients have received a Cypher stent. To date, FDA has received 47 Medical Device Reports (MDRs) of stent thrombosis occurring at the time of implantation or within a few days of implantation.”

Cordis sent a letter to healthcare professionals that week, notifying them of the incidence of thrombosis and reminding them of four important considerations with regard to using the Cypher: selection of the appropriate stent size; selection of appropriate patients for implantation; use of an adequate antiplatelet regimen to reduce the risk of clot formation; and the use of the proper technique for stent deployment. The third recommendation–the one related to blood clotting–would become a key element in the implantation and maintenance of drug-coated stents.

The news only got worse. On October 29, 2003, the FDA felt compelled to issue a second warning about the new device. The agency had by then received nearly 300 reports of adverse effects, 60 of which resulted in fatalities. In addition, there had been 50 reports of hypersensitivity and allergic reactions including pain, rash, respiratory alterations, hives, itching, fever, and blood pressure changes; several of these events proved fatal as well. Only a month later, the FDA provided updated numbers. They’d received 75 new reports of thrombosis and 20 new incidents of hypersensitivity. Meanwhile, Cordis had distributed nearly 600,000 Cypher stents by that point, pumping them out at well more than 100,000 a month.

Doctors and patients proceeded with little caution over the next year, putting aside fears of thrombosis and other complications, and the popularity of the drug-eluting stent continued to grow. After gaining FDA approval in March of 2004, Boston Scientific introduced its own drug-coated stent, the Taxus, coated with paclitaxel. On October 18, 2004, a year after it issued its second DES warning, the FDA announced its conclusion that there was virtually no difference in the thrombosis risks of drug-eluting stents when compared to bare-metal stents.

“The Cypher stent,” said the agency, “when implanted in accordance with the approved indications for use, is not associated with an excess of SATs [sub-acute thromboses] compared to bare-metal stents. SAT remains a relatively rare event that occurs within the first 30 days following the stenting procedure.”

While the safety of the DES may still have been questioned, the efficacy of the product was almost universally accepted: Drug-coated stents were instrumental in reducing the need for second surgical procedures. By the end of 2005, more than 90 percent of all stents being implanted in heart patients were drug-eluting stents.

Medical professionals were so thrilled that drug-coated stents reduced the risk of restenosis, they were perhaps willing to overlook the fact that the risk of stent thrombosis may have been growing. Several studies released in 2006 have brought the safety concerns back to the forefront of the discussion.

The first significant study was the BASKET-LATE (Basel Stent Kosten Effektivitäts Trial-Late Thrombotic Events) trial, which was set up to assess rates of cardiac death and myocardial infarction (MI) in stent patients who stopped using clopidogrel, the anti-clotting drug sold under the brand name Plavix. The randomized observational study fitted 499 patients with a DES and 244 with a BMS. According to the study results, in the year after clopidogrel discontinuation, patients with drug-eluting stents were twice as likely to suffer late stent thrombosis as those with bare-metal stents. Researchers also concluded that the risk of cardiac death or MI with the use of drug-eluting stents was “significantly higher” than the risk with the use of bare-metal stents: 4.9 percent versus 1.3 percent in the year after clopidogrel discontinuation.

Dr. Matthias E. Pfisterer created quite a stir when he first presented these results in March of 2006 at the Annual Scientific Session of the American College of Cardiology in Atlanta, and since that point, the debate has only gotten more heated. In September, the issue commanded center stage at the European Society of Cardiology/World Congress of Cardiology meeting in Barcelona, Spain, when three separate European studies questioned the long-term safety of drug-eluting stents.

The major presentation was made by Dr. Edoardo Camenzind of the University Hospital in Geneva. Dr. Camenzind conducted a meta-analysis of nine clinical trials and more than 5,000 patients to determine the risks of the DES versus the BMS. Camenzind found that the incidence of death or heart attack was higher for DES patients than for BMS patients–and higher for Cypher patients than for Taxus patients. Cypher patients were as much as 30 to 40 percent more likely to suffer serious adverse events than those with bare-metal stents while Taxus elevated the risks roughly 5 to 10 percent.

A second meta-analysis came from Dr. Alain J. Nordmann of the University Hospital in Basel. In this study, researchers examined 17 randomized trials and found that the Cypher was associated with significantly higher rates of noncardiac death when compared to bare-metal stents. The ThoraxCenter of Rotterdam presented its own study, which tracked stent thrombosis rates in more than 8,000 patients. Dr. Peter Wenaweser reported the cumulative rate of thrombosis was 2.9 percent, not terribly significant, but the troubling news was that the risk of thrombosis did not seem to lessen over time. Instead, the risk associated with DES patients continued to increase at the same rate (roughly 0.6 percent) year by year.

The biggest bomb at the September conference in Barcelona was dropped by Boston Scientific itself. The stent manufacturer announced that its own internal research had found a slightly higher, statistically noteworthy risk of blood clotting in patients who received their Taxus drug-eluting stents when compared to those who’d been implanted with bare-metal stents. Their review looked at 3,500 patients and included four years’ worth of data to determine the risks of late stent thrombosis (blood clotting in the stent area from the period beginning six months after implantation). Their admission was the first of its kind by any of the stent makers.

Immediately following the Barcelona meetings, the FDA decided to issue a new statement regarding drug-eluting stents. “We are aware of recent data suggesting a small but significant increase in the rate of death and myocardial infarction (heart attack) possibly due to stent thrombosis (a blood clot in the stent) in patients treated with DES,” the agency said, specifically citing the BASKET-LATE trial and Dr. Camenzind’s meta-analysis. “The small but significant increase in the rate of death and myocardial infarction observed in these studies was noted in patients followed 18 months to 3 years after stent implantation.”

The agency stressed the need for further studies and noted the importance of effective Plavix regimens to prevent clotting in DES patients. They also announced December’s public meeting of the Circulatory System Devices Advisory Panel to discuss the issues in greater detail. But ultimately, the agency was quite clear when it said: “At this time, FDA believes that coronary drug-eluting stents remain safe and effective when used for the FDA-approved indications. These devices have significantly reduced the need for a second surgery to treat restenosis for thousands of patients each year.”

The issue gained momentum in October at the Transcatheter Cardiovascular Therapeutics (TCT) meeting in Washington, D.C. A highly anticipated presentation by Drs. Gregg W. Stone and Marty Leon further clouded the medical issues at hand. Yes, they said, drug-eluting stents were indeed associated with significantly higher rates of late stent thrombosis. Yet, notably, they also claimed that the mortality rates among DES patients were no higher than those of BMS patients. That was largely because BMS patients were more than twice as likely to suffer re-clogging of their arteries.

With the debate raging on and contradictory evidence mounting, the stage was set for the FDA’s public meeting in December. The fate of the $6 billion DES industry largely hung in the balance.

The FDA’s public meeting of the Circulatory System Devices Advisory Panel on December 8 and 9 was not without its own share of controversy.

For one thing, the FDA decided to use physicians with a monetary stake in the products they were reviewing on behalf of the agency. Six doctors on the advisory panel had financial links to stent makers Johnson & Johnson and Boston Scientific; the FDA granted conflict-of-interest waivers to all six of the physicians in question.

“The reality is that the FDA sees industry as its client,” notes Jason Mark, the Parker & Waichman attorney. “The interests of the FDA are too often aligned with the interests of industry, and it’s the patients who time and time again suffer the consequences.”

Considering who was chosen for the panel, perhaps it’s not surprising that the group recommended, for the most part, a wait-and-see, business-as-usual approach. The panel did recommend new label warnings highlighting the increase in the risk of sudden heart attack or death in DES patients. Yet, in its own inimitable way, the FDA managed only to complicate matters by adding fuel to both sides of the DES argument.

While some physicians feel the devices may be too risky for the marketplace, others feel that the new warnings may discourage potential DES recipients who would truly benefit. Meanwhile, new studies continue to emerge with regard to the increased risk of thrombosis in DES patients; a recent Cleveland Clinic review assessed the risk of thrombosis in DES patients as being four to five times greater than that of BMS patients.

With millions and millions of patients already having received drug-coated stents–some estimates put the total number of DES patients as high as 6 million–even a very small increase in the risk of thrombosis becomes all the more significant. Writing in Cardiosource, the website of the American College of Cardiology, Drs. Sanjay Kaul and George A. Diamond noted that, based on the available evidence, drug-eluting stents may be responsible for more than 2,000 additional deaths every year when you consider the fact that roughly 1 million Americans per year receive a DES.

“Our romance with new technology–DES being only the most recent instance–is entirely understandable,” Drs. Kaul and Diamond write. “Technological innovation accounts for much of the miracle in modern medicine. It is entirely understandable, then, that: 1) device companies should want to develop new technology and support clinical trials necessary for regulatory approval and marketing so as to profit from the sale of that technology in a capitalistic market; 2) medical investigators should want to perform and publish such studies as a way to advance their careers; 3) insurance companies should want to rely on this information to justify reimbursing hospitals and physicians for utilization of that technology lest they be charged with restricting access to care in return for reducing their costs; and 4) hospitals and physicians should want to employ such state-of-the-art technology, and that patients should demand its use–even before long-term outcome trials confirm the short-term promise of that technology.

“Together, all these individually understandable incentives conspire to introduce promising new technology too quickly into the medical marketplace and to encourage its rapid overutilization. It is not at all surprising, then, that conflicts should exist between clinical practice and its evidentiary support, and that many DES interventions are thereby insufficiently justified.”

While those two doctors don’t believe a recall or moratorium on DES is necessary, they do support further FDA review and the resulting labeling changes as well as “a more accurate, timely, and comprehensive post-market surveillance program.” They also believe the FDA should be doing more to curtail off-label uses, which still account for more than half of DES implantation. “Although the FDA does not have the mandate to impact medical practice,” they note, “it should nevertheless leverage its relationships with medical professional societies and device sponsors to collaborate on the development and implementation of new tools and programs that help mitigate unnecessary risk and promulgate best practice standards.”

If nothing else, the DES debate has assured that most healthcare professionals will be more vigilant and discerning when addressing the risks and benefits of DES usage. Based on the available findings, doctors should only recommend drug-eluting stents for patients with a high risk of restenosis or those patients who cannot or will not handle long-term antiplatelet therapy. Doctors should not be afraid to employ bare-metal stents in certain cases where the DES may prove too risky. (Since bare-metal stents can be three to four times cheaper than drug-coated stents, the issue may have financial ramifications as well.)

The use of clopidogrel (Plavix) has proven to be essential to the long-term health of DES patients. However, the FDA has not yet approved the drug for that usage, meaning that DES recipients must use the drug off-label. Mostly all parties agree that extending the antiplatelet therapy in DES patients may be necessary in order to prevent dangerous blood clotting.

As with any new drug, therapy, or device, long-term side effects may take years to reveal themselves. The hope is that the increased scrutiny facing drug-eluting stents will lead to better decisions by the medical community, further research by the manufacturers, and greater understanding and awareness on the part of patients themselves.

Study finds `intriguing evidence' of stents' danger

Sat, 30 Dec 2006 00:00:00 -0800

After months of alarm over the small but potentially fatal risk of blood clots forming in the coronary arteries of people who have been implanted with drug-coated stents, researchers say they may have discovered why the tiny devices can become deadly.

Drug-coated stents may hinder the heart's natural ability to form tiny collateral blood vessels that can salvage heart muscle by rerouting the blood supply, according to a new study.

This little-understood process, which is known as nature's bypass system, seems to be stunted by the medicine that coats the stents, but not by bare-metal stents, according to Swiss researchers whose study will be published Tuesday in the Journal of the American College of Cardiology.

In a study of 120 patients, there was 30 percent to 40 percent less collateral blood vessel function in those implanted with the drug-coated stents, compared with bare-metal stents, six months after implantation.

The researchers theorized that this deficit could result in more serious damage to the heart in the event an artery abruptly closed such as when a clot occurs.

"Our results show that drug-eluting (coated) stents may hamper the heart's ability to salvage its own muscles," senior author Christian Seiler, a professor and physician at University Hospital in Bern, Switzerland, said in a statement. "... This could lead to a more severe heart attack."

The study presents some "very intriguing evidence," said David Marks, an associate professor of medicine at the Medical College of Wisconsin and director of the cardiac catheterization laboratory at Froedtert Hospital in Wauwatosa, Wis.

"They are speculating from very compelling and well-done data," Marks said.

Marks said the study provides more reason for doctors to make sure they have selected the correct stent for patients with coronary artery disease.

Medical College researchers now are in the midst of their own five-year study to try to find genes linked to the heart's ability to grow new blood vessels when blockages occur.

The $6 million study funded by the National Institutes of Health will use heart catheterization films and blood samples from heart patients. About 1,200 patients from the Milwaukee area are expected to be enrolled in the study.

"Some patients develop very vigorous collaterals," Marks said. "Other patients don't."

The difference may explain why some people survive heart attacks and why others die.

The hope is that if a gene or genes are discovered, drugs that aid the process of collateral blood vessel formation may be developed.

Because the field of collateral blood-vessel formation is so poorly understood, no one suspected the results from the new study, said Morton Kern, a professor of medicine at the University of California, Irvine.

"It is one other potential downside to drug-eluting stents," Kern said.

The study likely will focus more attention on the process of collateral blood-vessel formation as well as developing new generations of drug-coated stents that don't hinder that process, he said.

When drug-coated stents became popular in 2003, they were heralded as a major breakthrough in treating heart disease. The tiny, expandable mesh-like tubes were shown to be far superior to bare-metal stents in preventing the gradual re-blockage of arteries, a troubling but seldom fatal process known as restenosis.

Drug-coated stents are covered by medicine that slowly dissolves and that can dramatically reduce the formation of scar tissue that can re-block an artery.

About 1 million Americans are implanted with stents each year and an estimated 80 percent of those devices are drug-coated.

However, in recent months researchers and regulators have amassed evidence that in a small number of patients drug-coated stents were associated with the formation of potentially deadly blood clots up to two years later.

Studies suggest that clot formation, a process known as thrombosis, occurs in 0.6 percent to 2.6 percent of patients who get drug-coated stents. Thrombosis is more common when a patient discontinues taking blood-thinning drugs.

Doctors say that even with the recent alarms about drug-coated stents, the devices still are worth the risk when used in the appropriate setting. Compared with bare-metal stents, the drug-coated devices can substantially lower the risk of an artery re-narrowing with scar tissue.

At the same time, criticism has been leveled at some cardiologists for being too quick to use the devices, especially in so-called off-label circumstances where the devices are implanted for conditions in which clinical trials have not proven their effectiveness and safety.

Drug-coated stent use results in an estimated 2,160 excess deaths in the U.S. each year, according to an October editorial in an online journal of the American College of Cardiology.

"Surely, it is time to refine the use of this innovative technology so that its benefits outweigh its cost and potential for harm," said the editorial written by two California doctors.

At the University of Wisconsin Hospital in Madison, doctors already have become much more cautious in their use of drug-coated stents because of the recent reports of clots forming in the devices, said Giorgio Gimelli, director of the hospital's cardiac catheterization laboratory.

Doctors had been using drug-coated stents about 90 percent of the time, but that has dropped to about 75 percent in recent months, he said.

"This has given us cold feet a little bit," said Gimelli, an assistant professor of medicine. "We've changed practice fairly significantly."

The new study on how drug-coated stents may affect collateral blood vessel formation adds another reason to be cautious, he said.

"We'd prefer not to see it, but it's there and we'll have to deal with it," he said.

Hospitals revert to older stent models as FDA investigates new ones

Tue, 12 Dec 2006 00:00:00 -0800

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.

Panel weighs in on stents

Sat, 09 Dec 2006 00:00:00 -0800

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.

FDA Panel Seeks Warning That Stents May Be Unsafe

Sat, 09 Dec 2006 00:00:00 -0800

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.

Analysis: Panel urges warning on stents

Fri, 08 Dec 2006 00:00:00 -0800

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.

Feds questions experts on drug-coated stents

Thu, 07 Dec 2006 00:00:00 -0800

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.

Safety of Drug-Coated Stents Spotlighted

Thu, 07 Dec 2006 00:00:00 -0800

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.

Stents' Day in the Sun

Thu, 07 Dec 2006 00:00:00 -0800

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."

FDA Explores Safety of Heart Stents

Thu, 07 Dec 2006 00:00:00 -0800

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.

Drug-coated stents facing hard 2d look

Wed, 06 Dec 2006 00:00:00 -0800

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 heart of a stent debate

Wed, 06 Dec 2006 00:00:00 -0800

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."

Controversy Swirls Around FDA Meeting on Stents

Tue, 05 Dec 2006 00:00:00 -0800

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.

FDA: Stent patients face blood clot risk

Tue, 05 Dec 2006 00:00:00 -0800

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.

Controversy Swirls Around FDA Meeting on Drug Coated Stents

Tue, 05 Dec 2006 00:00:00 -0800

New scrutiny for stents

Mon, 04 Dec 2006 00:00:00 -0800

The tiny lattice-like props that keep arteries open and blood flowing freely come under scrutiny this week when the U.S. Food and Drug Administration holds a two-day meeting on drug-coated stents.

Also known as drug-eluting stents, the devices arrived on the medical scene with great fanfare in 2003 when they were approved by the FDA.

Now, a spotlight has been trained on coated stents because after three years on the market, doctors are finding that some of the 6 million patients with them worldwide are developing potentially dangerous clots. The FDA will determine whether the stents require further study or added warnings.

Word that clots were associated with drug-eluting stents first surfaced in September at an international meeting of cardiologists in Barcelona, Spain. There, researchers presented data showing that clots were occurring as late as three years after coated stents were put in place.

Burt Cohen, director of Angioplasty.org, a consumer advocacy group, said his Web site, which maintains a blog and posts reports about coated stents, has received 90,000 hits a day since September.

Doctors are noticing that patients are paying attention to the news. "It has changed my practice slightly," said Dr. Stephen Green, associate director of the catheterization laboratory at North Shore University Hospital in Manhasset. "But I talk to my patients, and for most of them the drug-coated stent is the stent of choice.

Green, citing federal statistics, estimates that only three to four people per every 1,000 receiving a coated stent will experience late-stage clotting.

When risks and benefits between drug-coated stents and the bare metal variety are weighed, Green said, the drug-coated devices still come out looking much better.

There are two brands of coated stents on the market. One is called the Cypher stent, manufactured by Cordis, a division of Johnson & Johnson. The other, the Taxus stent, is made by Boston Scientific Corp.

After placement of the Cypher stent, patients must take baby aspirin and the anti-clotting drug Plavix for three months; the Taxus stent requires six months of the medications.

"I don't think they'll go so far as a black box warning because there has not been a serious increase in deaths," said Dr. Kirk Garratt, clinical director of cardiovascular research at Lenox Hill Hospital in Manhattan. A black box warning is the highest level of FDA warning.

Dr. David Brown, chief of cardiovascular medicine at Stony Brook University Hospital, thinks a black box warning is out of the question. "My guess is that a couple of things will come out of the meeting: One would be to take Plavix for a longer period than currently recommended."

Dr. Robert Califf, a heart specialist at Duke University, who will provide one of the many scientific papers to be presented at the FDA meeting on Thursday and Friday, said the devices were implanted faster than scientists could collect data.

"As is frequently seen with new cardiac devices, a rapid increase in clinical adoption quickly outstripped what is known about the device from limited clinical trials," he said in a statement Friday.

FDA Probes Safety of Popular Heart Stent

Sun, 03 Dec 2006 00:00:00 -0800

Millions of chest pain and heart attack sufferers thought they were getting a phenomenal medical advance when tiny coils that ooze medicine were placed in their arteries to keep them from squeezing shut again.

These gizmos, called drug-coated stents, worked so much better than plain old metal ones that 6 million people worldwide received them in the few years they have been available. It was a modern record for any medical device.

Now their long-term safety is in question.

Doctors think these stents may raise the risk of life-threatening blood clots months and even years later unless people stay on Plavix, an anti-clotting drug whose long-term safety in stent patients has not been established.

Thousands of people are being urged to take the $4-a-day drug until more is known.

Thousands of others each day who develop new blockages are being treated by doctors no longer sure of what to do. Many are returning to the old metal stents, and some are fundamentally rethinking when to use stents at all and are considering alternatives like bypass surgery or medications.

A Food and Drug Administration panel will meet on the issue Thursday and Friday. Medical journals are rushing studies into print, and powerful doctor groups are reconsidering treatment guidelines.

"It's such a huge public health issue with so many people involved," said Dr. Robert Califf of Duke University, who worked on one study to be presented to the FDA.

Doctors also worry about overreacting to a risk that appears small five or fewer clots in every 1,000 patients.

"The benefit of having a drug-eluting stent is tremendous," said Dr. Elizabeth Nabel, director of the National Heart, Lung and Blood Institute.

Stents are used in angioplasty. Through a blood vessel in the groin, doctors push a tube to a blocked heart artery, inflate a balloon to flatten the clog, and prop the artery open with a stent.

About 652,000 Americans had angioplasty in 2003 more than twice the 268,000 who had bypass operations, which are riskier, costlier and take far longer to heal. Angioplasty became more popular when the first drug-coated stent came out that year, virtually eliminating the procedure's main drawback: scar tissue requiring a repeat effort to reopen the vessel.

Two brands are sold in the United States Taxus, by Boston Scientific Corp., and Cypher, by Johnson & Johnson's Cordis Corp. Labels say patients should take baby aspirin and Plavix for three months with Cypher and six months with Taxus, based on how long the stents release medication and how long doctors believed it took for the artery to repair itself by forming a new lining. Many doctors prescribe Plavix for up to a year.

Now it seems the coated stents may keep this essential artery lining from forming for a long time, maybe permanently. Without the lining or Plavix, clots can form and stick to stents.

It happened in May to David Reinhart, a 41-year-old legal secretary in Manhattan who collapsed two weeks after finishing the year of Plavix his doctor recommended.

"I feel a bit of a guinea pig," he said of the stent situation. "It's obvious there's a lot they really don't know about it yet."

If it weren't for Swiss efficiency, the risk might not be known. Switzerland's government required a study to prove the new stents were worth their cost $2,200 to $2,700 versus $600 to $800 for old ones and to test how long Plavix should be taken. This produced the bombshell finding that patients with coated stents had double the risk of cardiac problems after stopping Plavix than those with plain metal stents.

"Everyone has been scrambling around looking in their databases" to see if it's true in their patients, said Dr. Christopher Cannon of Brigham and Women's Hospital in Boston, who consults for Sanofi-Aventis SA, which sells Plavix in the U.S. with Bristol-Myers Squibb.

Many such hospital registry studies have now been reported. Two presented at a recent American Heart Association meeting were provocative.

Dr. Joseph B. Muhlestein at the University of Utah found that deaths and heart attacks were higher with coated stents after three years and that their advantage for preventing artery reclosure disappeared by that time. Doctors in the Netherlands found that the devices were comparable after three years.

"It's led me to wonder maybe we're being too aggressive" in using the new stents, Muhlestein said.

Hospital registries help, but are not solid proof like randomized studies where similar patients are assigned to get one treatment or another. The best picture yet of risk may come from an analysis of pooled results from 14 randomized studies by Dr. Deepak Bhatt at the Cleveland Clinic. Published Wednesday in the American Journal of Medicine, it found that coated stents had five times the risk of clots as plain metal ones.

Some doctors say stents were approved based on studies that were too small, too short and in low-risk patients. Doctors also have used them for cases other than the types of blockages for which they were approved. Success is being further undermined by many patients quitting Plavix too soon.

"They just don't understand how important it is to continue," said Dr. Sidney Smith of the University of North Carolina, past president of the American Heart Association.

Longer Plavix treatment now is being urged "a little bit to get the doctor off the hook," said Dr. David Williams of Brown University. "We're saying indefinite for some patients even though we have no idea what that means" in terms of safety, he acknowledged.

"I find that a very unsettling recommendation," said Dr. Spencer King, a cardiologist at Fuqua Heart Center in Piedmont Hospital in Atlanta and past president of the American College of Cardiology.

Plavix carries a risk of serious bleeding, he noted. Requiring coated stent patients to take it indefinitely puts them at risk of a clot if they have to temporarily stop Plavix to prevent excessive bleeding before a hip replacement or other surgery. Already, there are reports of people suffering such clots when going off Plavix for colonoscopies.

Many people can't afford Plavix. Medicare doesn't cover it unless people have the supplemental drug benefit, and half of angioplasties are done in people over 65.

"In the whole saga, the most important thing comes down to whether the patient is going to take Plavix or not," said Dr. Samin Sharma of Mount Sinai Medical Center in New York.

More research is needed to clarify the drug's role, Cannon said.

"There's a risk that's there when you don't have (Plavix). What we don't have are studies that show what's the risk with it," he said.

FDA panel to probe clotting, new stents

Thu, 30 Nov 2006 00:00:00 -0800

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 next week, hospitals that once embraced the new stents are starting to retreat to an older, cheaper version.

Drug-coated stents are implanted in nearly 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 in which doctors use a balloon-tipped catheter to open pathways to the heart.

Arteries treated with the first bare metal stents had a 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 so impressed 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 Wednesday, based on research led by The Cleveland Clinic, showed a four- to fivefold increased risk of clots compared with the bare metal variety of stent.

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 the patient 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 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 patients implanted with stents received the drug-coated version. 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 vascular business earlier this year for more than $4 billion. Abbott currently has a drug-coated stent in development for U.S. patients.

Big business

Only two drug-coated stents are on the U.S. market: Boston Scientific Corp.'s Taxus and Johnson & Johnson's Cypher. Both have lost sales. Although Abbott has a drug-coated stent in some European countries, analysts say Johnson & Johnson and Boston Scientific dominate the $6 billion worldwide market.

Drug-coated stents are big business. They can cost $2,200 or more each, compared with $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 a year, doctors 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 is worrisome, he said clotting after the stent has been in the artery for several months or even longer than a year affects "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 the angioplasty procedure itself.

FDA intervenes

The FDA has convened a special panel for next week to look at the clotting issue. The meeting was scheduled to discuss heart devices, but the clotting issue 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 a 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 implanted with different systems.

"It's not just any one component of a drug-eluting stent that matters it's the whole system," said Abbott spokeswoman Kelly Morrison.

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 of 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 percent to 10 percent of patients, compared with 20 percent to 25 percent for the bare metal variety. By comparison, 30 percent 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. .

Doctors say they encourage patients who have drug-coated stents to take aspirin and a common anti-clotting drug known as Plavix for up to six months or longer. The pills can cost $3 to $4 a day if they do not have drug coverage.

"A combination of aspirin and Plavix is extremely important," said Rush's Schaer. "We are more conservative about using the drug-coated stents in patients who are less compliant ."

Cleveland Clinic Analysis Finds Patients With Drug-Eluting Stents Are at Increased Risk for Late Thrombosis

Wed, 29 Nov 2006 00:00:00 -0800

There is as much as a four- to five- fold increased relative risk for late thrombosis, or blood clot formation, in patients with drug-eluting stents compared to those with bare-metal stents, according to a Cleveland Clinic-led meta-analysis published in the December issue of the American Journal of Medicine. This is the first published analysis of its kind.

Drug-eluting and bare-metal stents are commonly used to treat patients with coronary artery disease. There has been a growing body of evidence that drug-eluding stents, when compared to bare-metal stents, may increase the risk of blood clot formation long after they are implanted, potentially triggering a heart attack.

"Our analysis found 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 Deepak L. Bhatt, M.D., Associate Director of the Cleveland Clinic Cardiovascular Coordinating Center and one of the study's authors. "This does not, however, 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."

Fourteen studies with 6,675 total patients were included in the analysis comprising nine sirolimus stent trials and five paclitaxel stent trials. Eight of the trials reported more than a year of clinical follow-up. The sirolimus trials mandated anti-clotting medication for at least two to three months and the paclitaxel trials required six months.

"The key to the controversy is likely careful patient selection," Dr. Bhatt said. "Further research is needed to determine how best to utilize drug- eluting stents and anti-clotting medications."

This analysis precedes an FDA Advisory Panel set to meet next week in Washington, D.C. The committee will discuss and make recommendations regarding issues related to stent thrombosis in coronary drug-eluting stents.

Cleveland Clinic Heart & Vascular Institute is the recognized world leader in diagnosis and treatment of cardiovascular disease. Cleveland Clinic has been ranked No. 1 in the nation for cardiac care by U.S. News & World Report every year since 1995. Cleveland Clinic has been ranked among America's Ten Best Hospitals every year since 1990 by U.S. News & World Report.

Cleveland Clinic, located in Cleveland, Ohio, is a not-for-profit multispecialty academic medical center that integrates clinical and hospital care with research and education. Cleveland Clinic was founded in 1921 by four renowned physicians with a vision of providing outstanding patient care based upon the principles of cooperation, compassion and innovation. U.S. News & World Report consistently names Cleveland Clinic as one of the nation's best hospitals in its annual "America's Best Hospitals" survey. Approximately 1,500 full-time salaried physicians at Cleveland Clinic and Cleveland Clinic Florida represent more than 100 medical specialties and subspecialties. In 2005, there were 2.9 million outpatient visits to Cleveland Clinic. Patients came for treatment from every state and from more than 80 countries. There were nearly 54,000 hospital admissions to Cleveland Clinic in 2005. Cleveland Clinic's Web site address is www.clevelandclinic.org.

Drug-coated stents carry higher clot risk?

Wed, 29 Nov 2006 00:00:00 -0800

The Cleveland Clinic said its analysis found that patients with drug-eluting stents have a higher risk of late thrombosis.

In fact, the Ohio-based center said patients implanted with the drug-coated devices designed to prevent re-closing of the coronary artery, a condition known as restenosis may have as much as a four- to five-fold greater risk for late thrombosis, or blood-clot formation, compared to patients implanted with the earlier generation, bare-metal stents.

"Our analysis found 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 Deepak Bhatt, associate director of the Cleveland Clinic's Cardiovascular Coordinating Center and one of the study's authors.

"This does not, however, 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."

The meta-analysis focused on 14 studies involving 6,675 patients who had been implanted either with a sirolimus-coated or a paclitaxel-coated stent. Eight of those studies reported more than a year of clinical follow-up.

The patients with sirolimus-coated stents took anti-clotting medication for at least two to three months post-implantation, while the patients with paclitaxel-coated stents took clot-busting drugs for six months.

"The key to the controversy is likely careful patient selection," Bhatt said. "Further research is needed to determine how best to utilize drug-eluting stents and anti-clotting medications."

The study appears in the December issue of the American Journal of Medicine.

Millions face risk from drug-coated stents

Tue, 21 Nov 2006 00:00:00 -0800

Millions of Americans could be walking around with tiny time bombs in their hearts.

The concern centers on devices called drug-eluting stents. Doctors implant them in the hearts of about a million Americans a year to treat coronary artery disease. They generate some $5 billion a year in sales for the two companies that make them. But they may be doing more harm than good.

Next month a panel of experts will try to advise the Food and Drug Administration on what to do about it. But many top doctors and scientists admit they are in uncharted waters with a frightening problem that was largely unanticipated. By one estimate the devices already kill 2,000 Americans a year and no one knows what the long-term danger will be.

To understand the potential hazard, it helps to look at the history of efforts to open the arteries to the heart when they get clogged with cholesterol-containing plaque. That blockage leads to shortness of breath and the chest pains called angina. If the artery closes completely the result is a heart attack with destruction of heart muscle and often death.

Beginning around 1980, doctors started using tiny balloons inserted on wires through the veins and guided by X-rays to push open the clogged arteries. This procedure, called angioplasty, often worked but with a problem. In about half the cases the artery would close up again within a few weeks or months, an outcome called restenosis. The re-shutting of the arteries occurs because the blood vessels respond to the treatment as if they suffered a slight wound. They try to heal by growing more cells which can clog the artery again.

Thwarting the body's own healing process

To solve the problem, starting in 1994, cardiologists put tiny pieces of wire mesh called stents around the balloons. These stay in place as a piece of scaffolding to try to keep the arteries open.

These helped, but not enough.

Cells still grew over the wire, and in 20 percent to 30 percent of the cases, the vessel clogged again.

Drug-eluting stents (DES) appeared as the next solution. These give off a drug that prevents cell growth, and for that, they work well. The restenosis rate fell to about 5 percent. In 2003, soon after the FDA approved them, drug-eluting stents captured most of the market, even though they cost about $2,000 compared to $800 for the bare metal version.

Then a new hazard started to appear.

Doctors began seeing patients suffer from heart attacks that seemed to be triggered by the new stents. Because the drug-eluting stents are so effective at stopping the cell proliferation inside the arteries, the DES's end up as a piece of metal sticking out in the artery. That creates a perfect place for a blood clot to form and instantly block the artery. The result? A potentially fatal heart attack.

Dr. Jeffrey Moses of Columbia University, who conducted some of the original studies of the DES's, estimates the danger of a blood clot at 1 in 500 patients a year. For every million of the devices implanted, that would add up to 2,000 clots a year although not all of them would be fatal.

But an estimate from Drs. Sanjay Kaul and George Diamond from Cedars Sinai in Los Angeles, published on the Web site of the American College of Cardiology, estimates that deaths from the new devices exceed 2,000 a year. Studies from Europe regard the danger to be many times higher. Because the devices are so new no one knows how long the hazard persists.

Already, many cardiologists are cutting back from using the devices. Sales are dropping dramatically. The FDA panel may well recommend they not be used at all.

Companies are searching for alternatives, including balloons that give off the drugs and would be removed at the time of the procedure, as well as stents that dissolve a few weeks after they are implanted.

What's next?
The big question now facing the FDA is: What should the estimated 4 million patients who already have a DES do?

The devices cannot be removed safely or easily. One preventive measure is to keep the patient on the blood-clotting medication Plavix for months or even indefinitely. But that medicine can cause severe bleeding, including a type of deadly stroke, and it costs more than $1,200 a year.

DES manufacturers Boston Scientific and Johnson & Johnson could end up rivaling Vioxx maker Merck as targets of lawsuits from people who suffer heart attacks.

The origin of this terrifying problem is that medical devices, like drugs, get tested for a few months in a few hundred or at most a few thousand of people before the FDA approves them.

Many experts are clamoring for better methods of assuring safety before devices like these go into millions of people for a lifetime.

Heart Stents Reconsidered by Medical Community

Wed, 25 Oct 2006 00:00:00 -0700

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.

Data: Drug-coated stents carry clot risk

Tue, 24 Oct 2006 00:00:00 -0700

Data presented at a Washington medical conference revealed that drug-coated stents create a higher risk of blood clots than traditional metal stents.

The data, presented at the Transcatheter Cardiovascular Therapeutics meeting, revealed that the drug-coated stents, manufactured by Boston Scientific Corp. and Johnson & Johnson, carry a statistically significant higher risk of blood clots that could lead to major heart attacks, The Wall Street Journal reported Tuesday.

The data were taken from 1,800 patients implanted with Boston Scientific Corp.'s Taxus stent and 3,500 patients implanted with Johnson & Johnson's Cypher stent. Analysis of the data revealed that the Taxus stent caused a 0.4-percent risk of blood clot, while the Cypher stent caused a 0.6-percent risk. While the percentages are small, experts said they are statistically significant. The experts said stent blood clots have a 70-percent chance of causing major heart attacks and deaths.

A Johnson & Johnson spokesman said the numbers "are subject to interpretation by a number of methodologies, some of which may yield significant differences at certain time points."

Drawbacks of drug-coated stents surfacing

Wed, 13 Sep 2006 00:00:00 -0700

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.

Study: Blood-clot risks higher in drug-coated stents

Fri, 08 Sep 2006 00:00:00 -0700

Boston Scientific found a slightly higher risk of blood clotting in patients implanted with its newer drug-coated stents compared with older bare-metal ver sions, a company spokesman said yesterday.

The medical device maker reported the finding of its own new study to the U.S. Food and Drug Administration shortly after completing an analysis in late June, and met with the agency Aug. 1 to discuss the finding, company spokesman Paul Donovan said.

The Natick, Mass. based company reviewed previous clinical data involving 3,500 patients to compare rates of clotting in patients with its Taxus stent compared with older stents that are not coated with drugs.

The drug coatings are intended to help prevent formation of scar tissue that can form new blockages after surgery to implant stents, which are metal-mesh tubes that prop open coronary arteries. But recent studies, including findings released Sunday at the World Cardiology Congress in Barcelona, Spain, have indicated drug-coated stents carry a higher risk of rare instances of potentially fatal blood clots.

Boston Scientific's review confirmed that a higher risk exists in Taxus, the company's top-selling product and one of just two drug-coated stents on the U.S. market. While the stents are often credited with helping prevent heart attacks and bypass surgery, the review found a statistically significant higher rate of so-called "late stent thrombosis," or clotting, with Taxus in a period beginning six months after surgery compared with bare-metal stents.

"We have seen a slight increase in late stent thrombosis, which a number of studies have clearly shown to be a class effect common to drug-eluting stents," Donovan said. "The important point is we have seen no increases in heart at tacks or deaths."

Nearly 6 million people worldwide now have the drug-lined ver sions from the two dominant drug- coated stent makers, Boston Scientific and Johnson & Johnson's Miami Lakes, Fla.-based Cordis unit.

New Brunswick-based J&J has said it sees no statistically significant risk of late thrombosis in Cy pher.

Some of the blood-clotting concern stems from the fact that bare- metal stents allow heart cells to naturally grow to cover the stent after surgery, providing a natural biological lining. Drug-coated ver sions can prevent tissue growth, which helps prevent blockages but apparently leaves exposed metal that can act as a clot magnet.

Boston Scientific confirms small risk of blood clots forming in drug-coated stents

Thu, 07 Sep 2006 00:00:00 -0700

Boston Scientific Corp. found a slightly higher risk of blood clotting in patients implanted with its newer drug-coated stents compared with older bare-metal versions, a company spokesman said Thursday.

The medical device maker reported the finding of its own new study to the U.S. Food and Drug Administration shortly after completing an analysis in late June, and met with the agency Aug. 1 to discuss the finding, spokesman Paul Donovan said.

Its shares fell 2.3 percent in midday trading.

Boston Scientific develops and makes the stents in Maple Grove and has a stent-making plant in Ireland.

The Natick, Mass.-based company reviewed previous clinical data involving 3,500 patients to compare rates of clotting in patients with its Taxus stent and those with older stents that are not coated with drugs.

The drug coatings are intended to help prevent formation of scar tissue that can form new blockages after surgery to implant stents, which are metal-mesh tubes that prop open coronary arteries. But recent studies, including findings released Sunday at the World Cardiology Congress in Barcelona, Spain, have indicated drug-coated stents carry a higher risk of rare instances of potentially fatal blood clots.

Boston Scientific's review confirmed that a higher risk exists in Taxus, the company's top-selling product and one of just two drug-coated stents on the U.S. market. While the stents are often credited with helping prevent heart attacks and bypass surgery, the review found a statistically significant higher rate of so-called late stent thrombosis," or clotting, with Taxus in a period beginning six months after surgery compared with bare-metal stents.

"We have seen a slight increase in late stent thrombosis, which a number of studies have clearly shown to be a class effect common to drug-eluting stents," Donovan said. "The important point is we have seen no increases in heart attacks or deaths."

The results will be published once complete data are available, he said. The finding was reported in The Wall Street Journal's Thursday editions.

Nearly 6 million people worldwide now have the drug-lined versions from the two dominant drug-coated stent makers, Boston Scientific and Johnson & Johnson's Miami Lakes, Fla.-based Cordis Corp. unit.

The Journal reported J&J has said it sees no statistically significant risk of late thrombosis in Cypher.

Shares of Boston Scientific fell 40 cents to $16.87 in midday trading on the New York Stock Exchange, near the bottom of the stock's 52-week range of $15.46 to $27.82.

Shares of New Jersey-based J&J fell 53 cents to $63.39 in midday trading on the NYSE.

Some of the blood-clotting concern stems from the fact that bare-metal stents allow heart cells to naturally grow to cover the stent after surgery, providing a natural biological lining. Drug-coated versions can prevent tissue growth, which helps prevent blockages but apparently leaves exposed metal that can act as a clot magnet.

Boston Scientific Shares Dip on Letter News

Tue, 23 Aug 2005 00:00:00 -0700

Federal regulators sent Boston Scientific Corp. a warning letter identifying "serious regulatory problems" in medical devices shipped from a Quincy, Mass., distribution plant, including heart stents sent to hospitals despite a quality control problem.

The U.S.Food and Drug Administration's disclosure of the letter on Tuesday sent shares of Boston Scientific down nearly 5 percent in morning trading to a new 52-week low.

A letter to the company dated Aug. 10 said FDA inspectors found "serious regulatory problems" during a nearly two-month inspection in Quincy that ended May 20. The letter cited problems in shipments of the Natick, Mass.-based company's Taxus drug-coated stents Boston Scientific's top-selling product as well as Vaxcel implantable infusion ports used to administer drugs and Symmetry catheters that insert medical devices.

Boston Scientific spokesman Charles Rudnick said on Tuesday the company "is actively working on every point raised in the FDA letter. We've completed corrective action in many areas."

While the company acknowledges shipping products that should not have left the Quincy distribution center, Rudnick said, "It's important to note that in every case pointed out by the FDA we had previously identified the problems discussed by the FDA through our quality control and taken appropriate action."

Rudnick said none of the problems with shipments cited in the FDA letter harmed patients. Eight Taxus stents that were shipped to five hospitals in January, even though they were in a batch that had previously failed to meet quality standards, were returned to the company before they were used, Rudnick said. The drug-coated stents failed to pass a test involving their release of drugs to prevent scar tissue from forming new blockages after artery-clearing surgery.

However, the FDA's letter, posted on the agency's Web site Tuesday, said the problems it cited "may be symptomatic of serious underlying problems in your establishment's quality system."

The letter said "these serious violations of the law may result in FDA taking regulatory action without further notice to you," including such possible steps as seizing product inventory, obtaining a court order to halt marketing of devices, or fining the company.

The FDA said Boston Scientific's response to the inspection findings "fails to address specific system-wide corrective actions that are necessary to bring your facility into compliance."

Rudnick said the Quincy center distributes most of the company's medical devices, which are produced at various manufacturing sites. He said the FDA highlighted only problems at the distribution center, not systemic problems in the company's manufacturing.

Boston Scientific last summer recalled nearly 100,000 units of the Taxus stent and another model not coated with drugs because of a manufacturing defect that the company has since fixed.

Stents are metal-mesh devices that prop open coronary arteries after surgeries to clear blockages.

Boston Scientific shares declined $1.31, or 4.8 percent, to $25.84 in morning trading on the New York Stock Exchange, where the shares had traded in a 52-week range of $26.50 to $40.20.

The Wrong Way to Run a Recall

Thu, 12 Aug 2004 00:00:00 -0700

Boston Scientific's (BSX) handling of its recent coronary stent recall is a case study in how not to respond to a product failure. Since early July, the company has been forced into not one, but three, separate recalls of its market-leading device. Because of a manufacturing glitch, now apparently fixed, the system for inserting the stent into a patient's artery has been linked to 47 injuries and 3 deaths. With the latest recall on Aug. 5, Boston has yanked a total of 99,200 stents.

Now, Boston Scientific Chief Executive Officer James R. Tobin needs to convince bruised investors, wary cardiologists, and anxious patients that the company's finally in control of the problem. That's critical, since nearly 40% of the company's estimated $5.7 billion in sales this year will come from its popular drug-coated stent, which accounts for the bulk of the recall.

DANGEROUS PROBLEM

While Boston, based in Natick, Mass., has already lost market share, its main rival, Johnson & Johnson (JNJ), has been plagued by its own stent-manufacturing problems, which have limited its supplies. That's why Boston has time to recover. Still, with J&J working hard to remedy its supply woes and a new competitor, Medtronic (MDT), planning to jump into the market, another misstep could jeopardize Boston's lead.

The clumsy recall already has damaged the company and its credibility. It was slow to identify the manufacturing technique that caused the problem, and, as a result, issued an initial recall that was too small. Boston's stock, which traded around $43 a share the day before the first recall on July 2, has slid to a recent $33. And Morgan Stanley analyst Glenn M. Reicin figures Boston has lost 10 points of its 70% market share in drug-coated stents.

Until the recent troubles, Boston was riding high after introducing its drug-coated stent, TAXUS Express2, in the U.S. earlier this year. That device which is used to prop arteries open after angioplasty is coated with a drug that cuts the risk that the artery will become reclogged. J&J had launched the first drug-coated stent in the U.S., CYPHER, a year earlier. Despite that lead, many cardiologists found TAXUS easier to use.

But TAXUS has been dogged by a dangerous problem. In some cases, the balloon used in the procedure to insert the stent into the artery doesn't deflate. That malfunction has also occurred with Boston's bare metal stents, which aren't coated with drugs and which also are included in the recall. The balloon problem can be dangerous, forcing cardiologists to perform emergency bypass surgery.

INDUSTRYWIDE ERRORS

The company says a manufacturing change made in May and June in plants in Minnesota and Ireland has fixed the problem. And improvements over the past year in quality controls should ensure the safety of up to 122,000 stents that were made before the manufacturing fix but not recalled. Still, the Food & Drug Administration is reviewing how Boston determined which products to recall and could demand further product withdrawals.

While Boston's executives have been making the rounds to reassure big hospital customers, some cardiologists remain wary. Dr. Richard W. Nesto, chairman of the department of cardiovascular medicine at Lahey Clinic in Burlington, Mass., which uses about 2,900 stents a year, says his group will continue to limit use of TAXUS. Says Nesto: "We want to wait longer and make sure nothing pops up."

It could be a lot worse for Boston. J&J's manufacturing woes have limited how aggressively it can court disgruntled TAXUS customers. The FDA sent J&J a scathing letter in April citing a series of deficiencies in the company's stent plants. What's more, says Merrill Lynch & Co. analyst Daniel Lemaitre, J&J's problems have slowed the company's development of its next-generation drug-coated stent. That could give a boost to Boston, which will soon begin testing of an improved version of TAXUS.

Still, J&J says it's ramping up CYPHER production. And with Medtronic likely to join the fray late next year, that could push down prices for the drug-coated devices, which now sell for about $2,500 apiece. If the competition comes on strong, that will be one more reason Boston can't afford another slipup.

FDA Seeks More Boston Scientific Data

Fri, 06 Aug 2004 00:00:00 -0700

A day after Boston Scientific Corp. expanded a month-old recall of its lucrative drug-coated heart stent, federal regulators met Friday with company officials and asked for additional data about the manufacturing defect that led to the recall.

The Food and Drug Administration also said it plans to inspect a stent manufacturing plant in Ireland. The examination would be similar to one last month at a Minnesota plant where the agency found no serious problems that could have contributed to the defect.

After meeting with Boston Scientific officials in Washington, the FDA's top medical devices regulator said he did not immediately see a need to widen the recall beyond the nearly 100,000 Taxus and Express 2 model stents already recalled.

"The preliminary indication is that these quality assurance measures are adequate to ensure the safety of the product," Dr. Daniel Schultz said in a conference call.

The agency will review new data Boston Scientific will share and may request a second meeting in person or by phone as early as next week, Schultz said. Among those attending Friday's meeting were Boston Scientific's chief executive James Tobin and Dennis Ocwieja, the company's top regulatory affairs executive.

Schultz also said the agency saw no need to take any action on another 100,000 to 200,000 Boston Scientific stents produced before April and May, when the company adopted manufacturing changes aimed at preventing the defect. Those stents have been shipped or await delivery, but are not believed to have the defect that led to the recall.

Friday's meeting came a day after the Natick-based company announced it was again expanding its stent recall. The move covered 3,000 Taxus stents that were not included in the initial nationwide recall of 200 units announced on July 2 and 85,000 others recalled July 16.

Boston Scientific said it determined that the 3,000 additional stents should have been included in the earlier recall because they may have the same problem that prompted the others to be recalled.

The expanded recall was ordered because the company discovered an inspection problem at a factory in Galway, Ireland involving stents produced in late April, company spokesman Paul Donovan said. The FDA inspection will be of the Galway facility.

The defect involves a balloon used to expand the metal-mesh stents into place in a clogged artery during surgery called angioplasty. In some cases, the balloon has failed to properly deflate, making it hard to remove from the body. The defect has been associated with three deaths as well as 47 serious injuries.

Boston Scientific shares closed down 69 cents, or 2.4 percent, at $33.21 Friday on the New York Stock Exchange, adding to a nearly 7 percent slide the day before.

The company's stock price is nearly $10 below its close on July 1, the day before the initial recall was announced.

In addition to about 88,000 Taxus stents, the recall covers 11,000 Express 2 bare-metal stents that are not coated with the slow-release drug that the Taxus model uses to help prevent build-up of post-surgical scar tissue that can cause new blockages. The Taxus was first introduced in February 2003 in Europe and approved for U.S. use in March.

FDA Inspectors Visit Boston Scientific

Wed, 21 Jul 2004 00:00:00 -0700

Officials from the Food and Drug Administration are inspecting Boston Scientific Corporation's manufacturing facility in Maple Grove this week, after the company's recent recall of a defective heart stent.

The inspection is a matter of course during a recall, FDA and company officials said Tuesday. Maple Grove is one of two facilities worldwide where the popular devices are made.

Last week, Natick, Mass.based Boston Scientific expanded an earlier recall of its Taxus drug-coated heart stent as well as a conventional bare-metal stent after problems with their delivery system surfaced. About 96,000 of the tiny mesh devices, used to treat clogged arteries, were involved in the recall.

About 300 of the company's sales representatives have taken to the road this week to reassure doctors that the worst of the problem is behind them. The affected stents have been linked to at least three deaths and 43 injuries.

Locally, Boston Scientific reps have pulled two-thirds of the Taxus supply from the shelves at United Hospital, Abbott Northwestern Hospital and Mercy Hospital, said spokeswoman Terri Dresen. Supplies are being restocked this week.

Affected stents also have been weeded out of the Minnesota Heart Clinic's supply at Edina's Fairview Southdale Hospital, said Dr. Stephen Battista, an interventional cardiologist.

The clinic also is fielding occasional calls from concerned patients who have received the stents. These patients are not affected by the recall because the problem with the device is related to its delivery system.

"Since bare-metal stents came out years ago, we've implanted thousands of them, and maybe 300 to 500 Taxus stents this year," Battista said. Doctors at the clinic have not encountered any major problems with the devices' delivery system, he said.

In the procedure, a balloon delivers the stent to the clogged area. Once in place, the balloon is deflated and removed. If the balloon fails to deflate properly and the blood flowing downstream is reduced or stopped, the risk of damage to the heart increases.

Other hospitals are being far more restrictive using Boston Scientific's devices. The Cleveland Clinic, for example, is restricting use of all Taxus stents, not just those from the affected batches, said Dr. Eric Topol, chairman of the Department of Cardiovascular Medicine. "We will very rarely use the device until the situation has been resolved," he said.

The company has been in contact with 1,200 major catheterization labs nationwide, and 18 of them have banned use of the stents altogether, said Boston Scientific spokesman Paul Donovan.

Meanwhile, some doctors have expressed concern that it is difficult to withdraw Taxus' delivery system once the stent is implanted complaints that seem heightened now that the device has been recalled. This trait, called "stickiness," surfaced soon after the stent's U.S. introduction in March.

"I don't think Boston Scientific has gotten to the root of all of the problem," said Topol of the Cleveland Clinic. "The stent is easy to get in but difficult to get out. It's unpredictable."

The Minnesota Heart Clinic's Battista said some degree of resistance is to be expected when removing the stent system. "You open up the balloon, and then when you close it, it's not going to be the same shape," he said.

Donovan said the company has heard about the stickiness problem in the past, "but I'm not aware of a safety issue. It's more of a nuisance."

URGENT RECALL NOTICE - Immediate Action Required TAXUSTM Express2TM Paclitaxel-Eluting Coronary Stent Systems and Express2TM Coronary Stent Systems

Tue, 20 Jul 2004 00:00:00 -0700

Dear Risk Manager,

On July 2, 2004, Boston Scientific initiated a voluntary recall of two lots of TAXUSTM Express2TM Paclitaxel-Eluting Coronary Stent Systems after determining that units from these lots may have an increased likelihood of focal neckdown (narrowing) of the balloon deflation lumen, which could result in an increased possibility of a "no deflation" condition.

Upon additional analysis and investigation of "no deflation" complaints, Boston Scientific is extending the scope of this recall to include certain additional lots of the TAXUSTM Express2TM Paclitaxel-Eluting Coronary Stent Systems, as well as specific lots of the Express2TM Coronary Stent Systems. Units from these lots may also have an increased likelihood of focal neckdown of the balloon deflation lumen. This voluntary recall does not impact the safety of stents which have been implanted in patients. Patients with the Express2TM or TAXUSTM Express2TM stents should be reassured that this recall does not implicate the stent itself and their ongoing care is unchanged.

We are sending you this recall notification because our records indicate that your institution received one or more units of TAXUSTM Express2TM Paclitaxel- Eluting Coronary Stent Systems and/or Express2TM Coronary Stent Systems.

A "no deflation" complaint is defined as a reported failure of the delivery balloon to deflate within one minute. "No deflation" can cause significant patient complications including coronary artery bypass graft (CABG) surgery and death. Corrective actions associated with the root cause of the "no deflate" condition have been identified and were implemented after the manufacturing dates of the lots subject to this recall.

The information set forth on Attachment A to this letter describes the lots of TAXUSTM Express2TM Paclitaxel-Eluting Coronary Stent Systems that are subject to this recall. The information set forth on Attachment B to this letter describes the lots of Express2TM Coronary Stent Systems that are subject to this recall. Coronary Stent Systems having lot numbers that are not described on Attachments A or B are not subject to this recall.

PLEASE IMMEDIATELY DISCONTINUE USE OF AND SEGREGATE ALL UNITS FROM THESE RECALLED LOTS.

Please carefully review and follow the enclosed steps for Voluntary Recall and complete and return the enclosed Tracking/Verification Form.

Your local Boston Scientific sales representative can answer questions that you may have regarding this voluntary recall. Any TAXUSTM Express2TM Paclitaxel-Eluting Coronary Stent Systems returned will be exchanged, or at your request a credit will be issued. Any Express2TM Coronary Stent Systems returned will be exchanged, or at your request a credit will be issued.

Boston Scientific Widens Stent Recall

Fri, 16 Jul 2004 00:00:00 -0700

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.

Stent System Recalled After Defect Is Found

Sat, 03 Jul 2004 00:00:00 -0700

Boston Scientific Corp. yesterday announced a voluntary recall of two batches of its new drug-coated coronary stent system after a defect was linked to one death and 16 "serious" injuries.

The company's senior executives called the recall a precautionary measure during a conference call with analysts yesterday. The recall affects less than one out of every 10,000 Taxus Express2 stent systems on the market. Still, the recall comes just four months after the Food and Drug Administration cleared the Natick-based company to sell the medical devices in the U.S.

Jim Tobin, Boston Scientific's chief executive officer, reassured investors that the problem had nothing to do with the stent itself, but rather the catheter used to insert the miniature wire-mesh tubes into a patient's artery.

He said a recently discovered manufacturing glitch increased the likelihood that the catheter would fail to deflate a tiny balloon used to expand the stent, requiring physicians to immediately operate on affected patients.

Tobin said the design flaw did not guarantee failure for all of the 200 stents being recalled but increased the possibility of complications during the stent's insertion. Boston Scientific said the issue only posed a threat during angioplasty surgery, not to people who have already had stents successfully inserted.

Boston Scientific's stent has been on the market in Europe since February 2003 and in the United States since early March.

Out of the 445,000 Taxus stents inserted worldwide so far, the company said it has received 42 complaints of which only 30 Taxus systems showed actual performance flaws. The catheter problems appear to have been caused when too much heat was applied during the laser welding stage in the manufacturing process, the company said.

To rectify the problem, Tobin said a new stage of testing was added at the company's two manufacturing sites.

"The standard we aspire to is to never have a problem like this. We clearly didn't reach that standard in this case," Tobin said. "On the other hand, we're talking about two batches out of around two hundred and something produced so far."

Details about the Taxus-related death were not disclosed yesterday, although Tobin did acknowledge that the stent in question came from one of the faulty batches.

The recall will affect 200 stent systems sold to 99 U.S. hospitals and three Canadian hospitals. Boston Scientific spokesman Paul Donovan said he did not know whether any of those stents had been implanted.

FDA spokeswoman Sharon Snider said the agency was monitoring the company's voluntary recall but declined further comment.

Boston Scientific has generated about $490 million in revenue by selling approximately 220,000 Taxus stents in the U.S. Almost a third of that amount, or about $168 million, came in the month of June. Each device costs about $2,600.

Company officials said yesterday that it expected the two batches to be returned within 12 business hours. With Taxus' manufacturing process corrected, Boston Scientific said the original production cycle will be "flushed through" the market within two months.

The company didn't rule out the possibility of additional complaints in the near future.

"It's possible we that we may find another batch or two, but it's not likely," Tobin said. "We don't want to keep this a secret. It's a matter of keeping the doctors up to date."

The only other drug-coated stent on the market is Johnson & Johnson's Cypher product. Rivals such as Medtronic Corp. and Guidant Corp. hope in the next few years to introduce drug-coated stents they are developing into a global market that some industry estimates project could reach $6 billion by 2006.

J&J's stent also has had problems. In April, the FDA warned the company to quickly resolve problems with testing and documentation on Cypher stents manufactured in five different plants.

Deaths Spur New Caution From FDA On Stent Use

Thu, 30 Oct 2003 00:00:00 -0800

More than 60 patients who received a popular new drug-coated heart stent have died, the government disclosed yesterday a surprising increase since the last health warning about the device months ago.

The Cypher stent is a tiny metal scaffold used in patients with heart disease. It props open a cleaned-out artery but goes beyond other stents to emit a drug to reduce the chance the artery will clog again. But that drug does not prevent a different risk posed by all stents: blood clots that form around the devices and can cause a heart attack.

Sale of Cypher stents began in April; in July, the Food and Drug Administration warned that it had received reports of blood clots in 34 recipients, including five who died.

Yesterday, the FDA issued a second warning: It now has more than 290 reports of blood clots, and in more than 60 patients, the device was associated with death. Those clots occurred up to 30 days after the stent was implanted.

The FDA has also 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 patients died, but it did not say how many.

The cause of the problems has not been determined, the FDA said, stressing that it does not know whether the Cypher is riskier than a bare-metal stent. In studies that led to the Cypher's approval, it was found no more likely to cause blood clots than competing stents.

Some 260,000 Cypher stents have been distributed to U.S. hospitals and 180,000 abroad, making the number of problems reported small in comparison. Some of the increase in reports since July is likely due to increased publicity, FDA device evaluation chief Dan Schultz cautioned.

Cypher maker Cordis Corp. is conducting a 2,000-patient study that will track side effects. Enrollment is nearly complete, and data on blood clots should be available by the end of January, Cordis said.

Deaths from heart stent prompt warning

Thu, 30 Oct 2003 00:00:00 -0800

More than 60 patients who received a popular new drug-coated heart stent have died, the government disclosed, 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.

FDA Issues Second Warning On Side Effects From Popular New Heart Stent

Wed, 29 Oct 2003 00:00:00 -0800

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 began selling in April, and in July the Food and Drug Administration warned that it already had received reports of those blood clots in 34 Cypher recipients, including five who died.

Wednesday, the FDA issued a second warning: It now 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 yet 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.

Some 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 due to 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 physicians to promptly report any problems with Cypher recipients.

"We have a signal," Schultz explained. "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," noted 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 anti-clotting medication.

Cypher recipients must take anti-clotting 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' own 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.

Feds Link J&J's Stents To 60 Deaths

Wed, 29 Oct 2003 00:00:00 -0800

Federal regulators are linking Johnson & Johnson's blockbuster Cypher stent to more than 60 deaths in patients implanted with the device, according to an advisory issued yesterday.

For the second time since its approval by regulators in April, doctors were notified about problems associated with the stent, a medicated version of the tiny steel devices used to support arteries after angioplasty surgery.

The Food and Drug Administration's advisory reported a more than 10-fold increase in the number of cases of acute thrombosis, or blood clotting, in patients who received a Cypher stent. The number could actually be higher because of under reporting, a FDA official said.

But Barry Cohen, a cardiologist at Morristown Memorial Hospital, said the deaths had to be viewed in proper context. "The actual number of patients treated has also gone up dramatically," he said.

About 450,000 patients worldwide have received Cypher stents. Nearly 260,000 of those patients are in the United States.

"There is no procedure, whether you're using an old device or a new device, that is without complications," Cohen said. "If I needed a stent today, that's what I would ask for (the Cypher stent) for myself or my family."

Johnson & Johnson is banking on the Cypher stent to live up to blockbuster potential and deliver billions in revenues. With sales slipping on some of its top-selling drugs, the New Brunswick-based health care company, doesn't have a lot else to count on.

After overcoming initial problems meeting demand for the stent, the company now finds itself trying to get to the root of safety problems with the device.

Johnson & Johnson's shares fell yesterday to a 52-week low in heavy trading.

Three months ago, Cordis, a Johnson & Johnson subsidiary that developed the novel coronary device, issued a similar warning to physicians. The company reported five deaths and nearly 50 instances of serious blood clotting.

In its advisory to doctors, the FDA said it has received more than 290 reports of patients experiencing clotting within a month after receiving a Cypher stent. The FDA also has received more than 50 reports, including some deaths, that may be a result of hypersensitivity reactions, according to the agency's advisory.

Cordis said the rate of thrombosis, or clotting, remains lower than 1 percent worldwide. "The safety profile is still very positive," said Martin Schildhouse, a company spokesman.

The stock closed at $49.48, down $1.06, or 2.1 percent.

Analysts were hard-pressed to assess the impact the warnings might have on sales of the Cypher. Girish Tyagi of Thomas Weisel Partners in Boston, said he did not expect a slowdown in the use of the Cypher. "We maintain the clinical utility outweighs the risks," he said.

Tom Gross, who heads the FDA division responsible for monitoring products after they go to market, said data from clinical studies on the stent were "very reassuring" on the issue of clotting. Clotting occurs at a higher rate in bare metal stents, a precursor to the Cypher.

"Are these events in excess of what we might expect, we don't have any evidence to suggest that," Gross said.

The FDA relies on the public to provide information on any adverse effects. As a result of the passive nature of the system, Gross said there is an expectation that problems are under-reported.

"In one sense, we're aware of this potential problem," he said. "In another sense, we want to find out more. This is what we know about the situation at this point in time."

Clots Prompt Warning To Properly Use Popular New Heart Stent

Tue, 08 Jul 2003 00:00:00 -0700

Doctors got a stern warning Tuesday to properly use a popular new drug-coated heart stent that has been linked to blood clots in almost three dozen people, including five who died.

The Cypher stent is a tiny metal scaffold that props open a cleaned-out artery and, unlike other stents, emits a drug to reduce the chances the artery will clog again.

But the drug doesn't prevent a different risk posed by all stents blood clots that form around the device and can cause a heart attack.

The Food and Drug Administration has received reports of blood clots in 34 Cypher stent recipients. Five of those patients died, although FDA doesn't know if the clots actually caused the deaths, a spokeswoman said.

In a letter to more than 1,200 cardiac centres, manufacturer Cordis Corp. called the risk very rare considering 50,000 patients have received a Cypher stent since the eagerly awaited device began selling in April.

But Cordis cautioned that some of the clots happened after doctors improperly used the Cypher by choosing stents that were too small, implanting them improperly or not giving patients appropriate anti-clotting medicine afterward.

The Food and Drug Administration echoed that warning Tuesday.

In studies where Cypher was implanted under strict conditions, it proved no more likely to cause blood clots than long-used bare-metal stents, the FDA said.

It's not yet clear if clots among Cypher patients are occurring more often today than in those studies, said FDA cardiovascular devices chief Dr. Bram Zuckerman. He said clearly some physicians are incorrectly using the Cypher and should heed the following safe-use guidelines:

Cypher stents are only for new patients, not to replace a reclogged stent.

Recipients must take anti-clotting drugs for three months after getting the stent not the mere two weeks prescribed for bare-metal stents because arteries heal slower after Cypher insertion.

Closely match stent size to artery diameter. Demand for the Cypher greatly eclipsed supply when it debuted, and Cordis said it initially concentrated on making smaller sizes but now offers a larger size.

Be sure the stent is fully open, touching the artery wall.

Cordis will begin an FDA-ordered registry this month to further track Cypher outcomes.

Boston Scientific Drug Coated Taxus Stent Lawyer Blood Clot Risk

Tue, 08 Jul 2003 00:00:00 -0700

Boston Scientific Taxus Stent

The Boston Scientific Taxus Express Stent was approved in March 2004 and has made the company into the largest coronary stent manufacturer in the U.S. The stent emits paclitaxel, a drug intended to inhibit restenosis caused by scar tissue growth. The stent uses a proprietary polymer, Translute™, to control the release of the drug paclitaxel. In late November 2006, a new meta analysis by the Cleveland Clinic of 14 studies of drug coated heart stents found that the incidence of blood clots with these newer devices is four to five times the incidence associated with the original metal stents which eluted no drugs. Because of the increased risk of thrombosis and resulting heart attacks, patients with the paclitaxel-eluting Boston Scientific Taxus stent are required to take anti-clotting medications for six months or more. If you or a loved one have a Taxus stent and have suffered clotting as a result, contact Parker & Waichman, LLP for a free legal case consultation. Call 1-800-LAW-INFO (1-800-529-4636) or fill out the form at the right for legal assistance.

Taxus Stent Recalls
Boston Scientific Corp., the largest maker of heart stents, has had multiple voluntary recalls of its drug-coated Taxus devices because of defects in the delivery system. About 200 Taxus stents were recalled in July 2004. After identifying further problems, the company recalled 85,000 Taxus stents (both drug coated and bare metal types) later that month. In August 2004, an additional 3,000 Taxus stents were recalled that had been manufacturered prior to the aforementioned recalls. The catheter problems appear to have been caused when too much heat was applied during the laser welding stage in the manufacturing process, the company said.

If you or a loved one suffered injuries from a Boston Scientific Taxus stent, please fill out the form at the right for a free case evaluation by a qualified defective medical device attorney.