The FDA has issued an updated statement on the use of coronary drug-eluting stents (DESs) following a public meeting of the Circulatory System Devices Advisory Panel that was convened in Gaithersburg, Maryland, on December 7-8, 2006.

The FDA's initial statement, which related to concerns about adverse events related to DESs, was released on September 14, 2006, and was first updated on December 7, just before the meeting. The initial statement noted that new data suggested a small but significant increased risk of stent thrombosis in patients who have been treated with the currently approved DESs (Cypher, Cordis Corporation, a Johnson & Johnson company, Miami, FL; and Taxus Express, Boston Scientific Corporation, Natick, MA). The FDA stated that it has made detection of DES thrombosis signals a priority because of the potential for serious harm to patients, even though stent thrombosis occurs at low rates.

According to the FDA, the purposes of this meeting were: (1) to provide a forum for the presentation of clinical data relevant to the issue of stent thrombosis, both when DESs are used according to their label and in more complex patients beyond their labeled indication; and (2) to address the appropriate duration of antiplatelet therapy (aspirin plus clopidogrel) in DES patients. Panel members and public speakers represented a broad spectrum of interest and expertise, including interventional cardiologists, noninterventional cardiologists, cardiovascular surgeons, biostatisticians, and the DES manufacturers.

In response to specific questions posed by the FDA, the advisory panel presented its findings and recommendations regarding DESs when used in accordance with their approved indications. The panel concluded that, compared to bare-metal stents, both of the approved DESs are associated with a small increase in stent thrombosis that emerges 1 year after stent implantation. However, based on the data available, this increased risk of stent thrombosis was not associated with an increased risk of death or myocardial infarction (MI) compared to bare-metal stents. According to the panel, this finding may be due to either an insufficient number of patients in currently available studies, or an increase in deaths or MI was offset by a reduction in events associated with in-stent restenosis and additional revascularization procedures.

The panel stated that when compared to bare-metal stents, DESs are not associated with an increased rate of all-cause mortality. The concerns about thrombosis do not outweigh the benefits of DESs compared to bare-metal stents when DESs are implanted within the limits of their approved indications for use. The panel recommended larger and longer premarket clinical trials and longer follow-up for postapproval studies, using uniform definitions of stent thrombosis and close attention to patient compliance with antiplatelet therapy.

The panel was also asked to address the broader use of DESs in patients with more complex disease and coronary lesions compared to those patients studied to support initial marketing approval. The FDA stated that it believed that DES safety associated with off-label use should be included in the panel's deliberations, given observations that at least 60% of current DES use is off-label. The panel responded that with more complex patients there is an expected increased risk in adverse events, and it agreed that off-label use of DES is associated with an increased risk of stent thrombosis, death, or MI compared to on-label use. However, the available data were insufficient to determine whether the increased risk in adverse events with off-label use was the same or different in the two currently approved DESs. Data on off-label use are limited, and additional studies are needed to determine optimal treatments for more complex patients. The panel recommended that, until more data are available, the DES labels should state that when DESs are used off-label, patient outcomes may not be the same as the results observed in the clinical trials conducted to support marketing approval.

Regarding the duration of antiplatelet therapy, the panel noted that data from several studies suggest that a longer duration of antiplatelet therapy than is currently included in the Cypher and Taxus labeling may be beneficial. However, the optimal duration of antiplatelet therapy, specifically clopidogrel, is unknown, and DES thrombosis may still occur despite continued therapy. The panel said that the labeling for both approved DESs should include reference to the ACC/AHA/SCAI PCI Practice Guidelines, which recommend that patients should receive aspirin indefinitely plus clopidogrel for a minimum of 3 months in Cypher patients or 6 months in TAXUS patients, with therapy extended to 12 months in patients at a low risk of bleeding.

The FDA stated that it has been carefully considering the new data presented at the meeting, the opinions from public speakers, and the panel's deliberations and recommendations. The agency will be working closely with the manufacturers of both approved DESs and other DESs still under study to incorporate appropriate modifications to labeling and changes to pre- and postapproval studies. The agency said it will also continue to work with professional societies, consumer organizations, and health care providers to provide physicians and patients with the most updated information as quickly as possible.