What did the FDA say? Reviewing SAT and DES

The FDA panel met on December 7-8, 2006. Over the course of their meeting, it was agreed that the use of DES is not detrimental in approved cases. The panel acknowledged the data showed that DES did increase the likelihood of clot formation in some patients. The panel was concerned about off-label usage, especially in those patients who may have the potential for increased clot formation or those who are at high clinical risk. These concerns also extend to off-label use of bare metal stents as well. The main finding of the panel indicated that more research was needed to determine the long-term risk of DES for current indications. The panel expressed the opinion that indeed there was not enough data for definitive statement with regard to this problem. In the recent issue of the Journal of the American College of Cardiology, Pfistere et al described late clinical events after clopidogrel discontinuation as limiting the benefits of DES (J Am Coll Cardiol 2006:48;2584-2589). Similarly, a recent report from JAMA further suggests that patients should continue receiving Plavix for DES indefinitely and reduce the doubled risks of heart attack or death. FDA reviewer Andrew Farb said that the increased risk of acute stent thrombosis for DES was small but significant. The data reviewed at the FDA meeting demonstrated a modest increase in subacute thrombosis with DES, a finding which will have an impact on the next revision of PCI guidelines for the recommended duration of antiplatelet therapy in DES patients. The extension of the currently recommended time window of DES antiplatelet treatment from 3-6 months to more than a year certainly must be strongly considered despite having limited data on this particular recommendation. Current clinical practice being risk adverse suggests, at least in our center, that a minimum of 12 months or perhaps longer is prudent. The publicity around this issue has produced fear in many patients, who may consider their stent a time bomb waiting to cause trouble. If antiplatelet therapy is continued, the SAT risks are exaggerated out of proportion to the benefit provided. Because of these concerns, many interventionists are rethinking the indications for the use of DES and in more cases now reconsidering bare metal stents as an alternative, especially for those indications which lie outside the supporting data reported for the use of DES. One of my specific recommendations for careful use of DES includes the use of FFR for lesion assessment, particularly for marginal clinical indications, before putting in a DES which was previously considered to have no downside. Another older but still strong recommendation is the use of bare metal stents for vessels larger than 3.5 mm in diameter. Testifying to the FDA panel, Dr. Christopher White, chief of cardiology at Ochsner Clinic in New Orleans, indicated that he had heard nothing that was going to change his practice after returning from the panel meeting. Dr. Harrington and Dr. Califf, in their editorial accompanying the article by Pfistere (JACC 2006;48:2592-2595) asked the question, Should we be worried about the late ischemic events after drug-eluting stenting? They commented on the difficulty in demonstrating definitive excess adverse responses and further pointed to troubling changes in the world of clinical research which make it difficult to study the effects of DES thrombosis. Given the extensive use of DES around the world, we must question whether we are prepared to commit these patients to lifelong antiplatelet therapy with the risks of bleeding or ischemia after interruption. Wise clinicians should carefully consider the patient's ability to take the important antiplatelet regimen long-term. Failure to obtain appropriate medications because of social or psychological circumstances needs to be a consideration in patient and stent selection. Finally, what did the FDA say? Based on summary comments by William Maisel, MD, MPH, Assistant Professor of Medicine, Cardiovascular Division, Beth Israel Deaconess Medical Center, and Chairman of the FDA advisory panel, the outcomes from the meeting were the following: 1. There appears to be a numerical excess of late stent thrombosis with DES but the magnitude is uncertain. 2. There does not appear to be an increase in rates of death or myocardial infarction when the products are used on-label. 3. The off-label use of DES, like bare metal stents, is associated with increased risk compared to on-label use. 4. There is a need for more data to study the outcomes in more patients for longer periods of time. 5. The FDA should work closely with industry, academia and others in the evaluation of novel device technologies leading to device approval and expanded label indications. 6. Safety concerns like the SAT issue for DES underscore the need for a strong role of the FDA in public health policies.

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