More Warnings Given on Drug-Eluting Stents

By Alicia Ault

Despite the lack of solid, long-term safety data, the Food and Drug Administration and a handful of professional societies have issued new warnings that drug-eluting stents--which have been linked to late thrombosis--are not safe for all patients, and that the importance of maintaining dual antiplatelet therapy has been vastly underestimated.

In early January, the FDA announced on its Web site that it had "made detection of DES [drug-eluting stent] thrombosis signals a priority because of the potential for serious harm to patients [even though] stent thrombosis occurs at low rates."

The agency summarized the recommendations that were issued in December by its Circulatory System Devices Advisory Panel, including the observation that the off-label use of DES--estimated to be about 60% of device placements--is associated with an increased risk of thrombosis, death, or myocardial infarction (www.fda.gov/cdrh/news/010407.html).

Shortly thereafter, the Society for Cardiovascular Angiography and Interventions (SCAI) issued a clinical alert on DES (Cathet. Cardiovasc. Interv. 2007 Jan. 11 [Epub DOI: 10.1002/ccd.21093]). It had been in the works since early October, after data suggesting an increased risk of late stent thrombosis were presented at the European Society of Cardiology, said Dr. John Hodgson, chairman of the DES writing group, in an interview.

The alert is "a wake-up call," said Dr. Hodgson, SCAI past president and chief of academic cardiology at St. Joseph's Hospital and Medical Center, Phoenix. "We've gotten a little sloppy about putting stents in and not thinking through the entire process," he said.

Physicians should first determine if any procedure--whether surgery or stenting--is required, said Dr. Hodgson. If a DES is chosen, then intravascular ultrasound should be used to "document appropriate longitudinal lesion coverage and adequate stent expansion," according to the alert.

All risks and benefits--and the importance of maintaining dual antiplatelet therapy for at least 3-6 months, and for 12 months when there is little risk of bleeding--should be discussed with the patient.

Using a DES "can't be the default strategy," he said, noting that many patients are not appropriate candidates for the devices.

Lastly, the American Heart Association, the American College of Cardiology, SCAI, the American College of Surgeons, and the American Dental Association issued a joint science advisory on the dangers of premature discontinuation of dual antiplatelet therapy after DES placement. The advisory was published in Circulation (2007;115: [Epub DOI: 10.1161/CIRCULATIONAHA.106.180944]), the Journal of the American College of Cardiology, and Catheterization and Cardiovascular Interventions.

The recommendation has been to give 75 mg daily of Plavix (clopidogrel) and 325 mg daily of aspirin for 1 month after bare-metal stent implantation, for 3 months after sirolimus-coated DES implantation, for 6 months after paclitaxel-coated DES, and up to 12 months if there is a low risk for bleeding.

"That's gone out the door," said lead advisory author Dr. Cindy Grines, a cardiologist at William Beaumont Hospital, Royal Oak, Mich., in an interview.

The new recommendation is dual therapy for 12 months whenever possible, according to Dr. Grines. It has become clear that patients and physicians--primarily noncardiologists--are stopping therapy early, and that they may not understand the consequences, she said. Reasons for halting therapy include its expense (about $120 per month) and the perceived bleeding risk during a surgical or dental procedure, said Dr. Grines.

The AHA advisory urges physicians to discuss with patients the pros and cons of dual therapy and the need to continue it for at least 12 months. The advisory cited numerous studies showing that early stoppage led to a vastly higher rate of stent thrombosis, MI, and death.

Patients at particular risk for DES-related thrombosis--those who are older, or have acute coronary syndrome, diabetes, low ejection fraction, or renal failure--should consider taking dual therapy for as long as possible, according to the advisory.

If 1 year is not possible, or if patients are required to have invasive surgery within 12 months of the catheterization, then alternatives to DES--including a bare metal stent or balloon angioplasty--should be weighed.

And cardiologists need to be consulted before a patient stops antiplatelet therapy, even if they are asked to do so by another physician.

There may be benefits to dual therapy beyond 12 months, but with few solid studies, it was harder to get a consensus on extending the duration, said Dr. Grines.

Drug-eluting stents are not overused, she said, adding that this is especially true given that they've been shown to have an edge in restenosis.

"Personally, I still use drug-eluting stents in most of my patients," said Dr. Grines, noting that she makes exceptions for those who've had a recent MI, who have surgery scheduled, or who can't or aren't willing to maintain dual antiplatelet therapy for a year.

The FDA lauded the AHA document, saying it will raise awareness of the importance of dual therapy among all providers.

The AHA advisory "includes the critical message that patients who receive a drug-eluting stent need to remain on their recommended antiplatelet therapy," said an FDA spokeswoman in an interview.

But, she said, "the FDA is very interested in seeing that clinical studies are done to further address this issue."