FDA to issue document on drug-eluting stents

Also: U.S. Committee on Oversight and Government Reform requests information from Boston Scientific and Cordis.

WASHINGTON — At the Cardiovascular Revascularization Therapies 2007 meeting, a panel of industry, academia, FDA and professional society representatives discussed the issue of drug-eluting stent safety and appropriate evaluation studies.

The same week as the meeting, several papers relating to the safety concerns of drug-eluting stents – including data from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR) – were published in The New England Journal of Medicine, and a government committee requested data and marketing information from the two drug-eluting stent companies.

“We all need to appreciate that given that medical devices are becoming much more important for cardiovascular care, with that increased importance comes increased responsibility,” Bram Zuckerman, MD, director of the division of cardiovascular devices, office of device evaluation at the FDA, said at the meeting last month. “We don’t have a lot of answers right now, but just bringing them up today is an important first step.”

The FDA Circulatory System Devices Panel met in December and concluded that given the available data, when drug-eluting stents are used as indicated, they present no greater risk for late stent thrombosis than bare metal stents. Newer stents should stay in use with continued caution about off-label use. More than 60% of stent use is off-label.

The panel recommended that patients continue dual antiplatelet therapy, clopidogrel (Plavix, Sanofi Aventis; Bristol-Myers Squibb), for 12 months, and that further study of the risk for stent thrombosis is needed.

Current data

Martin B. Leon, MD, chairman emeritus of the Cardiovascular Research Foundation and professor of medicine at Columbia University Medical Center, said that 2006 data show that since 2004, the use of drug-eluting stents has dropped about 20% in the United States and 11% in Europe.

“We have several suggested objectives for the drug-eluting stent programs going forward,” said Andrew Farb, MD, medical officer, division of cardiovascular devices, at the FDA.

Those include determining rates of stent thrombosis over time, emphasizing safety endpoints such as death and MI, and exploring the current role of IVUS and angiography.

Farb said the FDA concurs with the device panel that antiplatelet therapy should be given for 12 months and wants more information on patient compliance with it, and whether patients continue to have thrombotic events on therapy.

“We do feel the panel recommendations apply to all the sponsors, both those that are approved and in various stages of development, but ongoing programs were based on the best FDA guidance at the time,” Farb said.

Remaining challenges are finding a common-ground definition for late stent thrombosis — although Farb said the Academic Research Consortium definition is acceptable for clinical trials — and figuring out the appropriate length of time to administer dual antiplatelet therapy. Farb said another issue is how to design a drug-eluting stent study to support a claim of safety and effectiveness in patients with diabetes and other high-risk groups.

Zuckerman and Farb said at CRT 2007 that the FDA plans to issue a guidance document within a year. Another workshop will be held in May.

New studies published

Published March 8th in The New England Journal of Medicine, data from the SCAAR show drug-eluting stents were associated with increased risk for mortality compared with bare metal stents; mortality and MI risk increased by 0.5% to 1% per year after the first six months. SCAAR includes data from every center that performs percutaneous coronary intervention and coronary angiography in Sweden.

“A generalized, unselective use of drug-eluting stents should be avoided, and a careful consideration of possible benefits and risks on an individual patient basis should be made when choosing stent type,” researcher Stefan James, MD, PhD, director of the cath lab and assistant professor of cardiology, department of cardiology, Uppsala Clinic Research Center, Uppsala, Sweden, said at CRT 2007. “An absolute 4% reduction in restenosis may be offset by a yearly 0.5% increase in mortality after the initial six months.”

Officials expressed caution interpreting the registry data and encouraged the need for randomized trials and long-term follow up.

Committee seeks information

Two days before the workshop at CRT 2007, U.S. Congress House of Representatives Committee on Oversight and Government Reform announced that Chairman Henry A. Waxman sent letters to Boston Scientific and Cordis requesting information on each company’s drug-eluting stent. Waxman seeks a host of research and marketing information, including the role the companies’ marketing departments played in stent studies and about the safety and off-label use of drug-eluting stents.

Waxman also requested marketing communication with professional organizations including the Cardiovascular Research Foundation, Transcatheter Cardiovascular Therapeutics and the Society for Cardiovascular Angiography and Interventions.

Waxman requested the documents by March 21. – by Judith Rusk

For more information:

• Farb A, Boam AB. Stent thrombosis redux — the FDA perspective. N Engl J Med. 2007:356;984-987.
• Lagerqvist B, James SK, Stenestrand U, et al. Long-term outcomes with drug-eluting stents versus bare metal stents in Sweden. N Engl J Med. 2007:356;1009-1019.