After bad news about the benefit of drug-eluting stents Johnon and Johnson and Boston Scientific aren't going to be happy about the news that drug-eluting stents, besides not being significantly more effective than non-coated stents, are generating safety concerns about risks of clotting in the drug-eluting stents.



A stent is used to open up an artery, usually the coronary or carotid vessels, that has become stenotic or closed, and restore blood flow. The problem is that after the vessel is opened, cells from the vessel wall will often proliferate and migrate into the stent causing the vessel to become stenotic or occluded again. The solution, many thought, was to coat the stents with drugs that would prevent proliferation and clotting. Bad news though, the drugs don't seem to be providing a significant benefit (news from the NEJM articles), and may actually increase the risk of clotting long-term.

From Business Week:

They're listening now. Over the past two years, doctors have noticed that patients with the new stents sometimes suffer fatal heart attacks months or years after the devices were inserted. At her nonprofit laboratory, the cvpath Institute in Gaithersburg, Md., Virmani, 64, has vivid microscope slides showing why: The victims' stents are totally blocked by clots. New analyses of the data from clinical trials, reported at a meeting last month in Barcelona, show that such late-occurring clots form more often with the new stents than with old bare-metal ones. In its own trials with its Cypher drug-eluting stent, J&J's Cordis division said in a written response that five patients have had late clots, compared with zero for bare-metal stents. The company says the difference is not statistically significant, but that "it is an important clinical challenge.

Prominent cardiologists like Nissen are calling for a large, long-term trial to figure out the size of this problem. The Food & Drug Administration terms it "a small but significant increase in the rate of death" and is convening a panel to examine the risks. Cardiologists estimate that the drug-coated stents may be causing 5 to 15 more clots per 1,000 people than the bare-metal stents. That's not a big number, but such a clot "is a catastrophe," explains Dr. Robert S. Schwartz of the Minneapolis Heart Institute; "100% of patients will have an infarction, and 20% to 40% will actually die. With millions of stents, that's a lot of catastrophes--10,000 to 30,000 patients per year."

And from the Times article:

Today’s reports, presented on Day Three of the annual Transcather Cardiovascular Therapeutics show here at the Washington Convention Center, included results from independent re-evaluations of death and heart attack data from clinical trials. The trials had been conducted by from Johnson & Johnson, Boston Scientific and a third company, Medtronic, whose Endeavor stent is sold in Europe but has not yet been submitted for approval in the United States.

There was also new data from two major studies in Europe, which tracked the outcomes for thousands of patients treated in Spain, Italy and Germay.

Reporting surprising findings from one of those studies, Dr. Alaide Chieffo, a researcher from Milan, said that Italian and German doctors who tracked more than 3,000 patients with drug-coated stents from 2002 through the end of 2004 found that the drug therapy widely thought to protect such patients from clotting had no beneficial effect after the first six months.

Many doctors, particularly in the United States where the drug-coated stents until recently represented nearly 90 percent of the market, commonly put patients on a regimen of aspirin and the anti-clotting drug Plavix for a year or longer. When Boston Scientific and others first reported evidence that long-term clotting seemed to be a rare but real risk with drug-coated stents, they said that risk could be managed by continuing that drug regimen.

Time to reconsider drug-coated or drug-eluting stents as a therapy. They are more expensive, require a more expensive drug regimen, and may not be providing a significant benefit, despite high-hopes they would be a revolution in percutaneous coronary interventions.