Because the safety fears were widespread, however, even those rooting hardest for a rebound — the companies that make stents — are not expecting a quick resurgence for the drug-coated devices. Worldwide, stent sales have fallen by about $1 billion since last year, to $5 billion this year.
In the United States, stenting procedures, whether using drug-coated stents or older bare-metal versions, have declined by about 10 percent in the last year. And within that smaller pie the share of drug-coated stents has shrunk even more, to about 64 percent in recent months, down from about 88 percent in the spring of 2006.
“It takes a lot longer to regrow a forest than to cut it down,” said Dr. Donald S. Baim, the chief medical officer for Boston Scientific, the market leader in stents.
While fears about the safety of drug-coated stents are seen as a major factor in the decline of stenting, studies showing good results in patients relying solely on drugs have also contributed to the decline.
Stents are among the most extensively studied products in the history of the medical device industry. But the torrent of performance data reflects the largely uncoordinated and piecemeal way that medical research is gathered and publicized, and the medical uncertainty than can result.
Drug-coated stents are the newest and most popular form of the tiny mesh cylinders, which are used to keep coronary arteries propped open after plaque blockages have been cleared through the procedure known as angioplasty. The drug coatings reduce the risk of reclogging at the stent site, as frequently happens with the bare-metal versions. But the studies last year indicated the drug-coated versions could cause blood clots months or even years after they are implanted.
The medical reports of blood clots were amplified by sometimes alarmist media coverage, as when one cable news network described drug-coated stents as “tiny time bombs.” And federal regulators weighed in, issuing cautionary statements about the clotting risk.
Doctors responded by prescribing long-term use of a potent anticlotting medicine for drug-coated stent patients — a course that raised costs and the risks of various side effects. Many patients avoided the stents altogether in favor of alternative treatments, including bypass operations, with their own attendant risks.
Now, though, for drug-coated stents “there really is a turnaround in the texture and the direction of the data,” said Dr. Eric J. Topol, a cardiologist at the Scripps Clinic in La Jolla, Calif. Dr. Topol was among those chosen by the Food and Drug Administration to serve on an expert advisory panel on stent safety last December, which concluded that the clotting hazard was real.
While none of last year’s concerns have been proved unfounded, Dr. Topol said, the newer data indicate that a return to higher use of drug-coated stents is appropriate “if you are going to practice evidence-based medicine.”
Some experts still contend that the lesson of the last year is that all but the sickest patients should think twice about getting any form of stent. The first effort with coronary artery disease, they say, should be making changes in diet and exercise, and taking drugs like statins to reduce cholesterol and beta-blockers to control hypertension and heart rhythm.
A report presented last week at the annual meeting of the American Heart Association concluded that stents often are of little use for patients whose only symptoms are occasional chest pains. That group includes at least 30 percent of those who typically get stents and perhaps considerably more, according to the lead author of the study, Dr. William S. Weintraub, the chief of cardiology at the Christiana Health System’s Center for Outcomes Research in Newark, Del.
Still, for the sickest patients, there seems to be little disagreement that stents can help. And now, after re-examining last year’s original clinical trial data and looking at studies involving tens of thousands of real-world patients, the common view is that there is no safety disadvantage in using drug-coated stents in most patients after angioplasty.
“Safety is not the big issue any more,” said Dr. Jeffrey W. Moses, a cardiologist in New York at Columbia University’s Cardiovascular Research Foundation, the organization that — with strong financial support from industry — runs the largest annual meeting for interventionalists, as doctors who use stents are known.
The worrisome clotting data were first reported at a March 2006 cardiology meeting. But wider attention was paid only after two more studies with similar conclusions were reported six months later at another meeting in Europe. A short time later, Boston Scientific reported that its own data confirmed the clotting hazard.
Even as anxiety rose among the more than 1.5 million Americans who already had the stents, most new stent candidates continued to get the drug-coated devices.
But cardiologists, newly cautious, placed those patients on a regimen of anticlotting drugs for a year or more, instead of the few months that had previously been standard practice. The drugs’ protection came with the risk of unwanted bleeding and at the cost of about $1,400 in prescriptions annually. This new regimen continues to be the recommended course of treatment, as a precaution against even the slight risk of clotting.
Meanwhile, tens of thousands of other American heart patients decided to avoid drug-coated stents altogether. Some of the sickest opted for bypass operations, with all the risks and discomfort that major surgery entails. Many more received bare-metal stents — older products that studies indicated were less prone to the clotting risk but that are often not as effective at keeping arteries open.
And still other patients, typically those with less severe symptoms like intermittent chest pains and shortness of breath, decided to rely entirely on cholesterol and hypertension drugs for relief.
One major influence on those choices was the warning last December by the F.D.A.’s expert panel that most of the drug-coated stents were being put in patients who were sicker than those who had been studied in the clinical trials. Those real-world patients, the panel worried, might be even more vulnerable to the clotting than the test patients had been.
But newer evidence indicates that while sicker patients do have higher clotting risks, they may also reap the greatest benefits from the drug-coated stents’ ability to keep arteries open longer. There are even hints that the stents improve survival rates for such patients.
When drug-coated stents reached the American market in 2003, some researchers predicted they could present unique clotting risks. But many doctors expected that the devices would save lives compared with bare-metal stents. Because the drug coatings made it less likely that the stent site would become reclogged, they reasoned, there would be less need for repeat procedures.
So it was unnerving last year when researchers began reporting that the newer stents might actually be less medically safe in the long run. The formation of clots long after the stents had been put in place became known as “late stent thrombosis” to distinguish it from the slight but already known danger of clotting that can occur during any stenting procedure or shortly after.
But now many advocates of the stents say the safety calculus may even be swinging in favor of drug-coated stents. They cite reports like a recently published study tracking 7,500 patients who received stents between 2003 and 2005 in Ontario. That study concluded that the sicker patients with drug-coated stents are experiencing lower death rates than comparable patients who got bare-metal devices.
The biggest American study yet, which has not yet been published but was presented Monday at the American Heart Association meeting, checked on the health after two years of more than 17,000 patients who received stents in Massachusetts from April 2003 to September 2005.
There was a clear safety advantage for drug-coated stents: 9.4 percent of the drug-coated stent patients had died, compared with 11.9 percent of those that got bare-metal stents.
But the uncertainties are likely to continue with newer types of drug-coated stents on the horizon. The new models have thinner struts and different coatings, which some studies suggest are less likely to lead to late stent thrombosis.
One new model, the Endeavor, made by Medtronic, may get clearance from the F.D.A. as early as next month. And Abbott Laboratories’ Xience V, which Boston Scientific will also market under the Promus name, may arrive by next summer.
Those stents and numerous others are already used overseas. But there are no long-term clinical trials that demonstrate they are better at saving lives. And some experts predict it will remain impossible to conduct trials that settle all the safety questions before the industry moves on to even newer designs — and new uncertainties.
