Heart Groups Issue Advisories for Reducing Drug-Eluting Stent RisksHeart Groups Issue Advisories for Reducing Drug-Eluting Stent Risks

New guidance on the use of drug-eluting stents for treating coronary vessel stenosis is intended to minimize a small but significant increased risk of stent thrombosis and death. Still, some experts voice concerns about the long-term safety of these devices.

The new advice for preventing thrombosis extends the recommendation for dual antiplatelet therapy (aspirin plus a thienopyridine such as clopidogrel) from the current 3 or 6 months (based on stent type) to 12 months. The guidance comes from three bodies, each with a slightly different perspective on the drug-eluting stent controversy.

The most recent guidance is a joint advisory on the dangers of discontinuing dual antiplatelet therapy during the recommended 12 months following device implantation. The advisory was issued January 16 by the American Heart Association (AHA), the American College of Cardiology, the Society for Cardiovascular Angiography and Interventions (SCAI), the American College of Surgeons, and the American Dental Association (http://circ.ahajournals.org/cgi/reprint/CIRCULATIONAHA.106.180944v1). It is being published in Circulation: Journal of the American Heart Association, Journal of the American College of Cardiology, and Catheterization and Cardiovascular Interventions (CCI): Journal of the Society for Cardiovascular Angiography and Interventions.

Earlier, on January 11, the SCAI issued a clinical alert that was published online as part of Catheterization and Cardiovascular Interventions (http://www.scai.org/pdf/DES%20clinical%20alert%20in%20CCI%20Feb07.pdf). The alert called for careful patient selection based on assessments of clinical history, lesion characteristics, and likely compliance with prolonged dual anti-platelet therapy. Physicians were encouraged to pay particular attention to stent implantation technique and to careful documentation of risk-benefit discussions. Overall, however, the alert sought to assure physicians and patients that “DES . . . remains a very effective method for the treatment for symptoms associated with the disabling problem of coronary artery disease.”

The professional societies' recommendations followed a December US Food and Drug Administration (FDA) statement calling for extension of dual antiplatelet therapy to 12 months for patients at low risk of bleeding (http://www.fda.gov/cdrh/news/010407.html).

Drug-eluting stents began replacing bare-metal stents as the treatment of choice after the FDA approved sirolimus-coated Cypher stents (Johnson & Johnson, New Brunswick, NJ) in 2003 and paclitaxel-coated Taxus stents (Boston Scientific, Natick, Mass) the following year. The FDA recommended that, at a minimum, patients receiving a sirolimus-coated stent receive 75 mg/d of clopidogrel and 325 mg/d of aspirin for 3 months. The same dosage, but for 6 months, was recommended for those receiving a paclitaxel-coated stent. At the time of approval, it was believed that the 3- and 6-month treatment courses would provide enough time for the stents to become endothelialized to avoid stent thrombosis.

Soon, however, anecdotal evidence emerged suggesting that 3 or 6 months of dual antiplatelet therapy did not adequately minimize thrombosis risk. Although FDA approval of the devices was for single lesions, some physicians were using these stents off-label in higher-risk patients with multiple lesions. Researchers raised the possibility that the presence of thrombosis could reflect the off-label use of stents in higher-risk patients. Some speculated that the area around the drug-eluting stent was not endothelialized after only a few months, providing a fertile ground for thrombosis.

Meanwhile, studies were uncovering some hard evidence. For example, patients with drug-eluting stents who stopped dual antiplatelet therapy before 12 months faced a mortality increase of 20% to 45%, the AHA's joint advisory noted. Other research found that 12-month regimens of dual antiplatelet therapy minimized late thrombosis. With such findings in hand, the professional societies and the FDA moved forward with their recommendations.

Raymond Gibbons, MD, AHA president, said the joint advisory is intended to clarify some of the misunderstanding and address fears patients may have after hearing news in 2006 about the dangers of drug-eluting stents.

“What we know is that therapy for that first year is beneficial,” said Gibbons, who is also a cardiologist at the Mayo Clinic in Rochester, Minn. “This important message got lost in all the publicity surrounding drug-eluting stents. There is no controversy here.”

Expressing similar sentiments is John McB Hodgson, MD, lead author of the SCAI clinical alert.

“We had patients walking in wondering what to do, so we wanted to put out realistic advice,” said Hodgson, who is also SCAI past president and Chief of Academic Cardiology at St Joseph's Hospital and Medical Center in Phoenix, Ariz. “What we put out is what we know and what we don't know, so it addresses the clinical questions our members are being hit with.”

But it is the “what we don't know” that concerns Steven Nissen, MD, president of the American College of Cardiology. Nissen, who was a member of the FDA panel that met in December, said off-label use of drug-eluting stents still comes with unanswered questions.

“Neither statement [by the professional societies] is designed to take a definitive position on the relative safety of drug-eluting stents,” said Nissen, a cardiologist at the Cleveland Clinic. “These devices were approved based on short-term trials. We don't have studies of quality to answer the question of relative benefits and risk.”

A key element to both the advisory and alert is the importance of careful advance discussions with the patient. If the patient cannot reliably take dual antiplatelet therapy for 12 months, then bare-metal stenting, coronary artery bypass graft surgery, or medical treatment should be considered. Reasons a patient may be unable to receive the therapy for a year may be medical, such as the likelihood of another surgery during that period, or socioeconomic, such as expense (clopidogrel costs about $4 per day, or $1460 for the year) or an inability to take medications on a daily basis.

Questions about the therapy also remain. While the 12-month regimen may work, longer durations have yet to be studied and may produce even greater benefit. Another issue is whether this situation eventually will disappear as second-generation drug-eluting stents with different properties come up for approval. Of course, studies will then need to examine long-term risk and benefit of these devices.