Lown Cardiovascular Research Foundation

Harvard Heart Letter | June 2008

Slow rehabilitation of drug-coated stents

New research supports the safety of drug-coated stents, but they aren’t for everyone.

It’s been a tough time for drug-coated stents. After being hailed as a revolutionary new therapy, these tiny wire cages fell from grace, tarnished by reports that they are responsible for a small number of heart attacks and deaths a year or more after implantation.

The downturn has been tough on the companies that make and sell stents, the doctors who put them in, and sometimes on the people who have one in a coronary artery. But it did force a more careful examination of the risks, not just the benefits, of these widely used medical devices.

The stent saga

Stents were invented to prop open arteries that balloon angioplasty had just cleared of cholesterol-laden plaque. The first stent was made of bare metal. It looked like a miniaturized chain-link fence rolled into a flexible tube. The collapsed stent was placed over an angioplasty balloon. When the balloon was inflated to open the artery, it also expanded the stent, pressing it into the artery wall.

Cells underneath a bare-metal stent gradually grow over its struts, like skin over a wound (see “Stent problems”). That’s good, because the covering of cells makes the stent look like part of the body. About one-third of the time, though, the cells don’t stop growing once the stent is covered, but grow into the open area through which blood flows. Such growth, called restenosis, can cut off blood flow to the heart muscle.

The drug-coated stent was designed to counter this problem. It releases a drug that slows the growth of nearby cells. The FDA okayed the first of these, the Cypher stent, in the spring of 2003. Within a mere six months, it was being used in half of all angioplasties requiring a stent. The second drug-coated stent, the Taxus, hit the market a year later. By 2006, the CypherThat’ and Taxus stents accounted for a whopping 90% of all stents used.

That was an extraordinarily rapid adoption for a new technology, particularly one that a person will live with for years but that hadn’t been studied beyond a year.

The dark side

Soon after drug-coated stents hit the market, doctors began seeing heart attacks and sudden deaths caused by blood clots forming inside the devices months after they were implanted. The drugs they exude (sirolimus from the Cypher stent and paclitaxel from the Taxus) prevent cells in the artery wall from covering the stent. Without this protective sheath, clots can form on the stent.

In 2006, preliminary studies from Switzerland and Sweden raised the alarm that this problem, called stent thrombosis, was twice as likely to happen with drug-coated stents as with bare-metal stents. That got the attention of doctors, and the media. The reputation of drug-coated stents fell from saving lives to “deliver[ing] heartburn,” as a Wall Street Journal headline put it.

The pendulum swings back

Much of the research since then has tilted in favor of drug-coated stents. A later, longer-term analysis of information from the Swedish study that raised an early alarm about stent thrombosis showed no significant difference in deaths and heart attacks among 19,000 people three years after receiving a drug-coated or bare-metal stent.

Dr. Laura Mauri, an interventional cardiologist at Harvard-affiliated Brigham and Women’s Hospital, and her colleagues found that after four years of follow-up, stent thrombosis rates were virtually the same — around 1.5% — for both drug-coated and bare-metal stents among participants in the major trials on which the FDA based its approvals. In a different study, of 17,000 Massachusetts residents who underwent angioplasty, 9.4% of those who got a drug-coated stent had died within two years, compared with 11.9% of those who got a bare-metal stent. Heart attack rates were the same, while repeat angioplasties were much lower in the drug-coated stent group.

So far, the most important step for keeping stent thrombosis at bay involves taking two clot-preventing drugs, aspirin and Plavix, every day for a year after getting a drug-coated stent or for 30 days after getting a bare-metal stent. No one knows if Plavix plus aspirin helps beyond these periods. This dual antiplatelet therapy, as it is called, isn’t totally benign. It can cause bleeding in the digestive system and elsewhere. It costs upwards of $1,500 a year. And it poses problems if you need surgery.

Where things stand today

The fruit of the scientific back-and-forth about the risks of drug-coated stents is a more thoughtful approach to their use tailored to the anatomy, health, and preferences of the people about to get them. Some folks are good candidates for a drug-coated stent; others might be better served by a bare-metal stent. Here are some very general guidelines:

A drug-coated stent might be for you if the anatomy of your blockage, or the artery it is in, might promote restenosis; if you don’t need elective surgery in the next year or so; and if you are good about taking medications.

A bare-metal stent might be a better choice if you might need to have an aneurysm or valve repaired, a hip or knee replaced, a breast or prostate biopsy, or other surgery in the next year or so; if you aren’t good at taking medications; or if you can’t afford to take aspirin plus Plavix. A bare-metal stent might also be a good option if you take warfarin (Coumadin) for atrial fibrillation, deep-vein thrombosis, or another condition, because warfarin, aspirin, and Plavix can be a tricky combination.

These recommendations are based on what we know today. They could change with results from ongoing research. New stents could alter the picture, too. Results presented at the American College of Cardiology meeting in March 2008 suggest that the Endeavor stent, which the FDA approved in February 2008, may rival or surpass the Cypher and Taxus stents for safety. Work on absorbable stents that prop open an artery for several months and then gradually dissolve could do away with worries about stent thrombosis (and maybe create new ones).

A final point to keep in mind: Do you really need angioplasty and a stent? For some people, medications coupled with exercise and a healthier diet may be just as good at easing mild chest pain as angioplasty, without the need for dual antiplatelet therapy or the small but real risk of stent thrombosis.