Off-Label Use of Drug-Eluting Stents

Abstract

Since Food and Drug Administration (FDA) approval of the first drug-eluting stent (DES) in April 2003, their use increased to 90% of all coronary stent procedures in the U.S. by 2006 (1). With restenosis virtually eliminated, DES were applied to increasingly more complex coronary lesions. However, over the past few years, reports of late stent thrombosis began to emerge. Additional reports of late stent thrombosis and increased mortality compared with baremetal stents (BMS) emerged from the European Society of Cardiology meeting in the fall of 2006 (2). These reports were eventually thought to be not entirely accurate owing to incomplete data and the methods of analysis. However, media attention, litigation concerns, and physician confusion resulted in a remarkable 42% decrease in the sales of DES over the next 6 months (3). Was the cardiology community overreacting, or was this drop in utilization of DES justified? See page 607The FDA ProcessTo address these concerns, the FDA convened the Circulatory System Devices Advisory Panel on December 7 and 8, 2006, to fully characterize the risk of DES thrombosis (4). They concluded that, compared with BMS, both types of FDA-approved DES (Cypher [Cordis, Miami Lakes, Florida] and Taxus [Boston Scientific, Natick, Massachusetts]) are associated with a small increase in stent thrombosis that emerges 1 year after stent implantation. However, this was not associated with an increased risk of death and MI (possibly owing to insufficient numbers or being offset by a reduction in events from prevention of restenosis and additional revascularization procedures). They concluded that concerns about thrombosis do not outweigh the benefits of DES when implanted for approved indication.The FDA panel also observed that at least 60% of current DES use is off-label, and off-label use is associated with increased events. However, they acknowledge that "with more complex patients there is an expected increased risk in adverse events" and noted that the FDA does "not regulate how [DES] are used by individual clinicians in the practice of medicine" (4).Although some have accused our regulatory agency of being too lenient, the FDA approval process is thought to be more arduous, expensive, and delayed than in most other countries (5). Even after initial FDA approval, expanding the approved indications is costly and requires 4 or more years of work (6). Some have estimated that excessive delays in FDA approval may have resulted in death in hundreds of thousands of patients and morbidity in millions of Americans (5).Although the current controversy surrounds off-label use of DES, even balloons and BMS have very limited indications (7). Moreover, aspirin, unfractionated heparin, and clopidogrel are not FDA approved for routine elective percutaneous coronary intervention (PCI). Clearly, an interventional cardiologist would not omit these important antithrombotic agents even though they are not FDA approved for PCI. Likewise, physicians must use their clinical judgment in deciding the best devic...

Outcomes of Bare Metal versus Drug-eluting Stents in Allograft Vasculopathy

“…13 This advantage over BMS catapulted DES use to 71% of coronary 14 but decreased significantly after concern for very late stent thrombosis. 15 The use of oral sirolimus to prevent restenosis was encouraging in both non-transplant patients 16,17 and CAV. 18 As a result, growing enthusiasm for the use of sirolimus-eluting stents in CAV ensued, but there has been conflicting data regarding their efficacy in preventing clinical outcomes or restenosis.…”

Improvements in Transcatheter Aortic Valve Implantation Outcomes in Lower Surgical Risk Patients

“…Similar to coronary stent use for off-label indications (1)(2)(3)(4)(5)(6), there is some evidence to suggest that patient selection criteria for transcatheter aortic valve implantation (TAVI) are evolving away from the premarket inclusion and exclusion criteria (7). This could mean that transcatheter aortic valves are implanted in higher or lower risk patients than those originally included in the initial safety and feasibility trials.…”

Blinded by Experience: Prior Experience, Negative News and Belief Updating

“…Given the procedural similarity of the drug-eluting stents to the existing bare-metal stents, and given the lack of a financial disincentive, the adoption of the drug-eluting stents was rapid and significant, rising to 90% of the entire cardiac stent market in a short period of time (Grines 2008).…”

“…To address these concerns, the FDA convened a panel of experts (the Circulatory System Devices Advisory Panel) to fully characterize the risks of the drug-eluting stents (Grines 2008). The FDA panel concluded that the risks of late stent thrombosis did not offset the benefits of drug-eluting stents, when used appropriately.…”