GAITHERSBURG, Md. -- Despite the sturm and drang over the thrombosis threats posed by the two first generation drug-eluting coronary stents, there is unflagging enthusiasm for new and improved devices.
GAITHERSBURG, Md., Jan. 15 -- Despite the sturm and drang over the thrombosis threats posed by the two first generation drug-eluting coronary stents, there is unflagging enthusiasm for new and improved devices.
When asked to predict the hottest topic in cardiology in 2007, Raymond Gibbons, M.D., of the Mayo Clinic, president of the American Heart Association, and Steven Nissen, M.D., of the Cleveland Clinic, president of the American College of Cardiology, and Christopher Cannon, M.D., of Harvard, principal investigator for the TIMI trialists, all had the same answer: drug-eluting stents.
Same Story, New Chapter
"This story is far from over," was the way Dr. Nissen put it. He was a consultant to the FDA Circulatory System Devices Advisory Panel that met here in December for two days on the safety of Cypher (sirolimus-eluting) and Taxus (paclitaxel-eluting) stents.
John Somberg, M.D., of Rush University Medical Center in Chicago, a member of that advisory panel, said the information spigot remains wide open.
And, in fact, a number of drug-eluting stent manuscripts are currently under review by several major journals. Moreover, the Society of Cardiovascular Angiography and Interventions released a clinical alert on drug-eluting stents last week. This week a drug-eluting stent statement is expected from a consortium of professional societies led by the American Heart Association.
More Long-Term Data
Fourth-quarter reports from Boston Scientific, maker of Taxus, and from Cordis, the Johnson & Johnson subsidiary that markets Cypher, indicated that by late 2006 drug-eluting stents were being used in less than 75% of percutaneous coronary interventions -- an ignominious end to a year that started with drug-eluting stents accounting for close to 90% of the procedures.
The FDA advisory panel recommended that the FDA request more long-term data from both companies in order to monitor drug-eluting stent safety.
Panel member Eric Topol, M.D. of Scripps Health in San Diego said long-term data would probably not be enough. He noted that establishing more patient registries could take three to five years for data collection and "that could just lead to more uncertainty."
In place of a registry of all drug-eluting stent patients, Dr. Topol proposed a narrower national registry of patients who have had late stent thrombosis. "We could look at the genomics of those patients, look at whether there was a predisposition to thrombosis, examine endothelial-cell issues involved in healing," he said.
Dr. Topol concluded that by collecting data on hundreds of patients who have had stent thrombosis researchers could "get a germ line, the genomic underpinnings, of this serious adverse event."
Daniel Schultz, M.D., director of the FDA's Center for Devices and Radiologic Health, said Dr. Topol's suggestions would be one of many panel suggestions that will be considered by the agency, but he declined any specific endorsement of the plan.
In the Pipeline
And while Cypher and Taxus stents face continued scrutiny, many in the interventional community consider them yesterday's news, as a number of second- and third-generation drug-eluting stents wend their way to regulatory approval.
For example, the Endeavor stent from Medtronic was submitted for FDA approval last Nov. 16.
The FDA advisers agreed that the FDA should require bigger clinical trials for longer periods of time and that those trials should also be designed to include information about the risk of stent thrombosis. But the panel didn't say how large the trials should be, nor did it specify an ideal time.
William H. Maisel, M.D., M.P.H., of Beth Israel Deaconess Medical Center in Boston, who chaired the advisory panel, said "we need data out to at least 12 months."
And post-marketing studies for second- and third-generation drug-eluting stents should also be longer, include more varied patients, and "include a control group," Dr. Maisel said.
But none of those criteria applied to Endeavor. Its application was based on the required three-month safety and efficacy data.
Dr. Schultz said the panel recommendations and any future changes in the requirements for FDA approval based on those recommendations would not affect applications already in process, i.e. the Endeavor stent.
At the hearing Rick Kuntz, M.D., senior vice president of Medtronic, presented a safety analysis of Endeavor based on clinical trials with 1,300 patients followed for up to three years.
Dr. Kuntz, and makers of other investigational drug-eluting stents, contended that stent thrombosis was not "a class-effect issue because there is no single drug-eluting stent class."
The newer generations of drug-eluting stents use different platforms, different drugs, and improved polymer coatings.
The safety data he presented appeared to back up those claims: the stent thrombosis rate for Endeavor was 0.30%, which represented a 30-day thrombosis rate of 0.5% to 1.0% and no late stent thrombosis.
In the completed trials patients were required to take three months of dual antiplatelet therapy, but Dr. Kuntz said that future trials will require six months of Plavix (clopidogrel) plus aspirin.
Also in the pipeline, and likely to be subject to changes in pre-market requirements, is Abbott's everolimus-eluting stent called Xience.
Safety data have not yet been reported on this stent, but in efficacy trials that compared it with Taxus, Xience demonstrated significant superiority as measured by late lumen loss (0.11 mm versus 0.36 mm late loss for Taxus, P