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GAITHERSBURG, Md. -- The FDA's drug-eluting stent advisory panel recommended today that the agency change the labels of the two approved coronary devices to warn that off-label use may increase the risk of thrombosis, myocardial infarction, and death.
GAITHERSBURG, Md., Dec. 8 -- The FDA's drug-eluting stents advisory panel recommended today that the agency change the labels of the two approved coronary devices to warn that off-label use may increase the risk of thrombosis, myocardial infarction, and death.
In the closing minutes of the two-day hearing, the special panel also recommended that the labels carry a recommendation that dual antiplatelet therapy with aspirin and Plavix (clopidogrel) continue for 12 months if the stents are used off-label.
The advisory panel agreed yesterday that when used as per label directions, drug-eluting stents were associated with an increased risk of stent thrombosis, although there was no evidence of increased risk of death or MI.
But when the panel turned its attention to off-label use, which represents 60% of the estimated three million Cypher (sirolimus-eluting) and Taxus (paclitaxel-eluting) stents implanted in Americans, the risk-benefit equation was not so easily balanced.
Several panel members suggested that a black box warning should be added to the stent labels, but Bran D. Zuckerman, M.D., director of the FDA's division of cardiovascular devices, quickly quashed that suggestion. "There will be no black box," he said.
And moments after the hearing adjourned, Daniel Schultz, M.D., director of the FDA's Center for Devices and Radiological Health, said there could be no label changes that reference off-label use.
One way around that regulatory roadblock would be to include a list of special populations-patients with multiple vessel disease, bifurcation lesions, overlapping stents, long lesions, or diabetes-that encompass the off-label cohort. Another option would be to include the warning in an FDA statement or letter to providers. Dr. Schultz did not rule out either option.
The panel also agreed that future pre-market clinical trials of drug-eluting stents "should be longer and bigger and should specifically address the issue of stent thrombosis," said William H. Maisel, M.D., M.P.H., of Beth Israel Deaconess Medical Center in Boston, who chaired the Circulatory System Devices Advisory Panel.
And post-marketing studies should also be longer, include more varied patients and "include a control group," Dr. Maisel said.
Asked how quickly the FDA would move on the panel's recommendations, Dr. Schultz declined to set a timetable. But while he indicated that the FDA would consider lengthening the duration of pre-market trials so that the issue of stent thrombosis can be addressed, he said that those changes would not impact the Endeavor stent, a new drug-eluting stent made by Medtronic.
The FDA is already reviewing the Medtronic data, which included nine-month follow-up.
Dr. Maisel said that he expected the FDA to require at least 12 months of data for future pre-marketing trials, but he said that for some stents nine months might be sufficient.
The control group, which should be included even in post-market registry data, could be patients who "were treated medically, or with bare metal stents, or with bypass surgery," he said. He added that another likely comparator group would be patients treated with another drug-eluting stent.
The panel also said there was a need for a clinical trial to determine the optimum duration of Plavix therapy.
Panel member Robert Harrington, M.D., of the Duke Clinical Research Institute, said the question could be answered with a trail that compared 12 months of Plavix to 18 months and 24 months.