Drug-Eluting Coronary Stents: Safety Concerns

ROCKVILLE, Md., Sept. 14 -- The FDA said today it will hold a special meeting of a device advisory committee to assess new data about "small but significant" increases in the rates of death and myocardial infarction among patients treated with drug-eluting coronary stents.

The agency said that its Circulatory System Devices Advisory Panel will meet before the end of the year to consider the implications of a meta-analysis reported in Spain and earlier data that suggested late-stenosis safely concerns with the devices.

In a statement, the agency added that it has already discussed safety concerns with the makers of the two FDA-approved drug-eluting stents-Cypher, a sirolimus-eluting stent sold by Cordis, a Johnson & Johnson company, and Taxus, the paclitaxel-eluting stent sold by Boston Scientific.

The FDA cited two recent studies, BASKET (Basel Stent Cost Effectiveness Trial), first reported in March at the American College of Cardiology meeting, and the Camenzind metanalysis reported this month in Barcelona at the European Society of Cardiology meeting.

The BASKET study found that at 18 months, the rate of death or myocardial infarction was 8.4% for patients treated with drug-eluting stents and 7.5% for bare-metal stents, but that difference was not statistically significant. (P=0.63).

By contrast, the Camenzind meta-analysis, which included three-year data, found a 2.4% increase in the incidence of death or MI in patients who received Cypher stents compared with patients treated with bare-metal stents (P=0.03).

The FDA said it will review those data and other pertinent information at the advisory panel meeting. It also signaled that it is seeking more information about the possible mechanism of the excess mortality and MI in patients with drug-eluting stents.

The hypothesis is that the events are caused by late stent thrombosis due to a failure of the stent to re-endothelialize, but that has yet to be proven.

The FDA statement said the agency is continuing to evaluate information related to the duration of dual antiplatelet therapy with aspirin and Plavix (clopidogrel).

"Although the duration of [Plavix] appeared to be adequate for the selected patients in the original clinical trials conducted to support FDA approval, the agency recognizes that the optimal duration of [Plavix] in more complex patients has not been defined," the FDA said.

The current American College of Cardiology/American Heart Association guidelines recommend an minimum of three months of Plavix plus aspirin for patients who receive Cypher stents and six months of dual therapy for those who have Taxus stents implanted. The ACC/AHA also recommends extending dual therapy for a year for patients with no known excess bleeding risk.

The FDA said more clinical studies will probably be needed to determine the ideal duration of dual antiplatelet therapy.

Meanwhile, the FDA offered reassurances about the safety of drug-eluting stents and said it "believes that coronary [drug-eluting stents] remain safe and effective when used in patients having clinical and coronary anatomic features similar to those treated in the pivotal trials conducted by the manufacturers for FDA approval."

Those approved indications are:

• The CYPHER Sirolimus-eluting Coronary Stent is indicated for improving coronary luminal diameter in patients with symptomatic ischemic disease due to discrete de novo lesions of length ? 30 mm in native coronary arteries with reference vessel diameter of ?2.5 mm to ?3.5 mm.
• The TAXUS Express Paclitaxel-Eluting Coronary Stent System is indicated for improving luminal diameter for the treatment of de novo lesions ?28 mm in length in native coronary arteries ?2.5 to ?3.75 mm in diameter.

Finally, the FDA said that for "thousands of patients each year, these devices have resulted in a significant reduction in the need of second procedures to treat restenosis." An estimated one million drug-eluting stents have been implanted in patients in the United States.