Are drug-coated stents safe?

It seemed like a breakthrough at first: Adding a drug to the tiny tube that props open a blocked artery after a common heart procedure, which slashes the risk of renewed narrowing and blockage of the blood vessel. Doctors rushed to use the new device, called a drug-eluting stent, which boosted the effectiveness of percutaneous coronary intervention (PCI), or angioplasty, in which a tiny balloon is inserted into a blocked artery. When inflated, the obstruction is pushed against the artery wall, the passageway widens, and blood flows freely.

Then came alarming news: Studies found that the drug might increase the chance of blood clots, a catastrophic complication with a high risk of causing heart attacks and death. In 2006 the Food and Drug Administration called for further study, and the use of these stents plummeted.

Now the pendulum has swung back, and for good reasons. New research has helped calm fears about the safety of the devices and clarified which patients fare better with them rather than the older, less-expensive bare-metal stents, which lack the drug coating. And while you may think a cardiologist will select the right stent for you based strictly on technical factors, you should understand the options clearly and, if time permits, express a preference when either device might work well.

After PCI, cells grow rapidly in an attempt to heal the vessel lining and envelop the stent, which the body considers a foreign object. In about 15 to 40 percent of the cases, depending on the complexity of the original obstruction, that reaction will narrow the artery again and cause another blockage of blood flow, usually within six to 12 months after the procedure. The renewed blockage, called restenosis, might cause the gradual onset of chest pain or acute coronary syndrome—sudden, severe chest pain that can result in a heart attack. A second PCI or even open-heart surgery could be needed.

The medication gradually released by a drug-eluting stent—such as sirolimus (Rapamycin) or paclitaxel (Taxol)—suppresses the inflammatory reaction that triggers rapid cell growth, thus reducing the chance of restenosis and repeat procedures.

In a study published in June 2009, researchers at the University of Minnesota and other institutions analyzed the combined results of 28 clinical trials. They found that second procedures on blocked vessels were needed in 21 percent of the patients who had bare-metal stents vs. 8 percent with drug-eluting ones—a relative reduction of 62 percent and an absolute reduction of 13 percent.

But by blocking cell proliferation, which leads to covering the stent with scar tissue, it may leave the stent exposed and thus more likely to develop a dangerous blood clot, called stent thrombosis. Such clots can occur long after PCI, particularly after the required preventive treatment with anticlotting medication—such as aspirin plus either clopidogrel (Plavix) or prasugrel (Effient) plus aspirin—is discontinued. Current guidelines recommend such treatment for a year.

The risk of stent thrombosis is almost identical during the first year for both types of stents. But a slightly greater risk persists after that with the drug-eluting stents, while it almost disappears with bare-metal ones, the Minnesota analysis found.

Reassuring Results

The key question is whether the benefit of reduced restenosis with drug-eluting stents outweighs the slightly higher risk of thrombosis. While there's still no definitive answer, much of the research now indicates that it does for most patients.

One of the studies that raised the initial alarm about stent thrombosis came from Sweden, where researchers tracked all patients who received coronary stents there for one year. However, in May 2009 The New England Journal of Medicine published results from a second, expanded study involving some 48,000 patients followed for up to five years. It found that those given a drug-eluting stent had lower restenosis rates than those who received the bare-metal type, with comparable rates of both heart attack and death for both devices.

In the most comprehensive analysis yet, published in June 2009, researchers at the Columbia University Medical Center evaluated evidence from 22 randomized and controlled trials involving nearly 9,470 patients. They calculated no increase in deaths or heart attacks between the two categories of stents. But according to Greg W. Stone, M.D., the study's author, roughly two of 10 patients given a bare-metal stent required a second procedure, while only one of 10 with a drug-eluting stent needed another procedure. That's an overall reduction in relative risk of about 50 percent and an absolute risk of 10 percent. So while drug-eluting stents don't seem to help patients live longer, they apparently can help at least some of them live better by decreasing the chance of renewed heart problems and procedures.

The study also addressed another major concern: the use of drug-eluting stents for unapproved, or off-label use, including the treatment of more-complicated blockages and for higher-risk patients than those enrolled in the trials originally submitted to the FDA. Such use accounts for well over half of all cases in real-world practice. The analysis suggested that off-label uses were generally as safe and effective as using the stents for the approved treatments, though further study is needed to confirm.

While there is much new evidence that favors drug-eluting stents in general, researchers have begun to identify the best candidates for each of the two types. Because the pros and cons of drug-eluting stents depend on many factors, the choice should usually be made on an individual basis. The main determinants are your risks of restenosis, bleeding, and thrombosis and, if time permits—as it can in many cases—your personal preferences.

"Your input is crucial in part because the likelihood of successful drug treatment to prevent thrombosis is the most important consideration," says Stone, director of cardiovascular research at Columbia University Medical Center. If you don't want to take anticlotting drugs for a long time because you think it would be too inconvenient, too hard to remember, risky, or expensive, you'll need a bare-metal stent. Brand-name drugs have a retail price of about $160 a month, but insurance coverage varies, so check with your provider. And the drug-eluting stent itself costs more, too: the retail price is about $2,000, vs. $800-$900 for a bare-metal stent.

In addition, the chance of restenosis in some patients is already so small that a bare-metal stent might work almost as well as a drug-eluting one without any increased thrombosis risk or anticlotting medication. Ideal candidates for an uncoated stent, with the least chance of restenosis, are people who don't have diabetes and have a short blockage in a large artery. Conversely, coated stents are best for people with diabetes and a long obstruction in a small vessel.

But even those who in theory should do reasonably well with a bare-metal device might prefer to get a coated one and take the medication, to obtain the somewhat greater protection against restenosis. And personal preferences count even more in the large gray zone between the two ideal candidates.

It's also crucial to give the cardiologist a complete medical history, since other factors may preclude a drug-eluting stent by making anticlotting drugs too hazardous. Those include having a history of serious bleeding, the use of other blood thinners, a heart-rhythm disorder called atrial fibrillation, and having a mechanical heart valve. Also tell the cardiologist if you're facing other surgery, which may require you to stop taking anticlotting medication, or if you have a weakened heart, which raises the risk of thrombosis.