The most exhaustive studies yet published on drug-coated stents show that the widely used heart devices are no better at preventing heart attacks and death than the older, cheaper devices they replaced, and in some cases may be slightly worse.
Since their introduction in 2003, the tiny wire tubes, about the size of a pen spring, have become fastest-selling medical devices in history, used in millions of people worldwide. They have been a boon to Boston Scientific Corp. of Natick, the largest life-science company in Massachusetts and one of the world's two major stent manufacturers.
However, safety concerns have emerged in the past year because drug-coated stents appear to carry a higher long-term risk of blood clots forming in the arteries that nourish the heart.
A series of studies released today by the New England Journal of Medicine showed that drug-coated stents carried one clear benefit: patients who receive them are less likely to return to the hospital for a repeat heart-clearing procedure.
Viewed over the long term, however, the stents did not improve patients' survival rates. And when Swedish doctors examined a computer registry of every Swedish stent patient for the years 2003 and 2004 -- nearly 20,000 people -- they found that patients with drug-coated stents were slightly more likely to die than those with bare-metal ones.
The information published today has been presented piecemeal at conferences and meetings over the past several months, most prominently at an expert panel convened in December by the Food and Drug Administration to discuss the long-term safety of the devices. But until now it had not yet appeared in any of the peer-reviewed journals widely read by doctors.
Dr. William Maisel, a cardiologist at Beth Israel Deaconess Medical Center in Boston who chairs the FDA's panel on cardiovascular devices, said the new studies would likely push doctors to be more cautious about using drug-coated stents. "The decision to put in a drug-eluting stent is now a decision, where before it was used in almost any case," he said.
Sales figures suggest doctors already are being more conservative about the use of drug-coated stents. Several months ago, many hospitals reported doctors were choosing drug-coated stents in as many as 90 percent of all procedures. A recent hospital survey suggested that number had dropped to 72 percent. In other countries, where drug-coated stents were never as widely adopted, the rates are lower still.
The drop in usage has triggered a stock slide for Boston Scientific, which depends heavily on the profits from drug-coated stents.
Stents are used in coronary angioplasties, a common artery-clearing procedure that has replaced bypass surgery for many patients as a way to restore blood flow to the heart. Typically patients receive one or more stents to keep cleared arteries open. The stent implant is permanent, sealing into the artery wall.
Drug-coated versions cost more than $2000, on average. Bare-metal stents typically cost $700. In its early trials, the drug-coated version clearly helped reduce the rate at which the arteries re-clogged. But as time has passed, long-term data show higher risks. The reasons are not conclusively known, although small studies on autopsied arteries suggest that the drug coating appears to impede normal healing of the artery wall.
Patients can minimize the risk of blood clots by taking aspirin and the blood-thinning medication Plavix, although doctors and the FDA have not reached consensus on how long the medicine should be prescribed.
Four of the articles published today are examinations of long-term data from the so-called "pivotal trials," the original stent studies sponsored by manufacturers. Overall, the articles found drug-coated stents were roughly as safe as bare-metal stents for the first year after the procedure, and helped patients avoid repeat procedures. Starting a year after the procedure, however, patients with drug-coated stents could expect a slightly higher risk of dangerous coronary blood clots. Overall heart attacks and death rates were roughly equivalent for patients with the two types of stents.
But those studies were limited to patients with relatively simple angioplasty problems. More than half of angioplasty heart patients in the US have more complex problems and it remains unclear whether they can count on the same results. The Swedish study, which analyzed a so-called "real-world" registry of patients, included a broader mixture of patients and found patients with drug-coated stents had an 18 percent higher risk of death than those with bare-metal stents.
In a statement, Boston Scientific said today that most of the study results confirmed its findings that drug-coated stents are safe and effective when used as approved by the FDA. A company executive singled out the Swedish study as "far from definitive" because it was an uncontrolled registry of patients rather than a randomized clinical trial.
Both Boston Scientific and Johnson & Johnson, the other major stent maker, are sponsoring further trials to assess the safety and effectiveness of stents in more complex patients.
Dr. Steven Nissen , chairman of cardiovascular medicine at the Cleveland Clinic and president of the American College of Cardiology, said the new papers highlight a "knowledge gap" in how stents really affect patients. "Even though drug-eluting stents have been implanted in millions of patients, they've only been studied in a few thousand," he said.
Nissen and Maisel said that the new results also point to a flaw in the system for distributing information about medical devices. Under current rules, companies control the data that emerges from studies they sponsor. After the clotting controversy erupted at medical meetings this year, both major stentmakers, Boston Scientific and Johnson & Johnson, released their data to independent researchers.
"It's not enough to collect that information," said Maisel. "It needs to be collected and shared."