Studies and several commentaries on drug-eluting coronary stents. 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
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.
Only patients with the simplest, least complicated cases of arterial stenosis
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.
It’s important to realize that stents are mainly effective for relief of angina
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.)
Drug-eluting stents have been an important advance in the management of coronary artery disease
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.