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FDA Statement on Coronary Drug-Eluting Stents

http://pharmalive.com/news/index.cfm?articleID=373031&categoryid=9&newsletter=1


ROCKVILLE, Md., Sept. 14, 2006-FDA is providing the following information in response to inquiries asking for the agency’s position on adverse events related to coronary drug-eluting stents (DES). This information describes our position at this time and does not represent new agency policy.

FDA has been closely monitoring DES since they came to the United States market in 2003 and 2004 – and will continue to do so.

We are aware of recent data suggesting a small but significant increase in the rate of death and myocardial infarction (heart attack) possibly due to stent thrombosis (a blood clot in the stent) in patients treated with DES. The specific studies that have prompted recent media inquiries are the BASKET-LATE study (presented at the March 2006 American College of Cardiology Scientific Sessions in Atlanta, Ga.) and more recently, the Camenzind meta-analysis (presented at the September 2006 European Society of Cardiology Annual Meeting/World Congress of Cardiology Meeting in Barcelona, Spain). The small but significant increase in the rate of death and myocardial infarction observed in these studies was noted in patients followed 18 months to 3 years after stent implantation.

While the studies presented at the Atlanta and Barcelona meetings have raised important questions, the data we currently have do not allow us to fully characterize the mechanism, risks, and incidence of DES thrombosis. A more formal evaluation of the data in these studies is necessary, and any conclusions are dependent upon a thorough peer review. FDA intends to more formally evaluate the studies presented in Atlanta and Barcelona.

Stent thrombosis in patients who receive DES is a primary area of interest for the agency because of the potential for serious adverse outcomes—even though stent thrombosis occurs at low rates. Over the past two months, the agency has met with both manufacturers of the FDA-approved approved DES to discuss any information and perspectives they have that may be pertinent to this issue. In assessing the risk of stent thrombosis, we remain keenly interested in the long-term follow-up of patients enrolled in the original pivotal DES randomized trials as well as those in the more complex patient and lesion subsets (for example, patients with diabetes; acute myocardial infarction or multiple vessel disease; or lesions involving arterial bifurcations, the left main coronary artery, and long arterial segments) who are currently being treated in “real world” randomized and registry studies.

FDA also continues to closely evaluate information related to the duration of treatment with clopidogrel (Plavix), a drug used in combination with aspirin to reduce/prevent clotting in DES patients. Although the duration of clopidogrel 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 clopidogrel in more complex patients has not been defined. The recommended duration of clopidogrel administration and patient compliance with the prescribed regimen are likely interrelated with patient and anatomical factors that are associated with DES thrombosis. Additional clinical data are likely needed to reach conclusions regarding the optimal antiplatelet therapy regimen for DES patients.

FDA will convene a public meeting of the Circulatory System Devices Advisory Panel by the end of the year in an effort to improve our knowledge regarding the incidence and timing of stent thrombosis as well as the appropriate duration of clopidogrel use in patients who receive DES. This Panel of outside experts will assist the agency in the review and analysis of the available scientific data and provide recommendations for appropriate actions to address this issue, such as possible changes to device labeling or the need for additional clinical studies. An announcement of this meeting will appear on FDA’s web site, www.fda.gov/cdrh.

At this time, FDA believes that coronary DES 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. The 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.

For more information, see http://www.fda.gov/cdrh/pdf2/P020026.html and http://www.fda.gov/cdrh/pdf3/P030025.html.

For thousands of patients each year, these devices have resulted in a significant reduction in the need of second procedures to treat restenosis. The FDA will continue to carefully evaluate all DES data in an attempt to maximize the benefits and minimize the risks for patients undergoing this therapy for treatment of their coronary artery disease.

To summarize:

FDA has been monitoring coronary drug-eluting stents closely since they came on the U.S. market in 2003 and 2004, and will continue to do so. New data were released recently that suggest a small but significant increased risk of stent thrombosis in patients who have drug-eluting stents. The agency is keenly interested in this issue because of the potential for serious harm to patients—even though stent thrombosis occurs at low rates. While the new data are of interest to FDA and raise important questions, we do not have enough information yet to draw conclusions. It’s unclear, for example, what causes drug-eluting stent thrombosis, how often it occurs, under what circumstances it occurs, or what the risk of occurrence is in a given patient. To better understand this issue, FDA met with the two manufacturers of these products in recent months to discuss any information they might have pertaining to this issue and get their perspective. In addition, we plan to convene a public panel meeting of outside scientific experts in the near future to assist us in a thorough review of all the data and make recommendations about what actions may be appropriate, such as possible labeling changes or additional studies. At this time, FDA believes that coronary drug-eluting stents remain safe and effective when used for the FDA-approved indications. These devices have significantly reduced the need for a second surgery to treat restenosis for thousands of patients each year.