Overview of the 2007 Food and Drug Administration Circulatory System Devices Panel Meeting on the Endeavor Zotarolimus-Eluting Coronary Stent

Abstract

Initial trials comparing stenting with balloon angioplasty demonstrated improved angiographic and clinical outcomes with the former.1–3 The main clinical problem with bare metal stents (BMS) became the development of in-stent restenosis.4–6 Early data suggested that drug-eluting stents (DES) could mitigate, if not abolish, this problem.7–9 Since the approval of DES, these devices have become the predominant stents used in percutaneous coronary interventions, regardless of indication. As of September 2007, the Cypher sirolimus-eluting stent (SES) (Cordis Johnson & Johnson, Miami Lakes, Fla) had been deployed in >3 million patients worldwide,10 and the millionth Taxus paclitaxel-eluting stent (PES) (Boston Scientific, Natick, Mass) was implanted as of January 2005.11 Over the past 2 years, numerous reports of very late stent thrombosis (ST) with first-generation DES have surfaced. This highly morbid complication and data suggesting that death and myocardial infarction (MI) may be more common with DES12,13 have altered the focus of trials and registries working to determine optimal DES use. There is a hope that second-generation DES will be less prone to ST as a result of differences in drug, stent design, and polymer. Medtronic, Inc (Minneapolis, Minn) presented safety and efficacy data to a public meeting of the US Food and Drug Administration (FDA) Circulatory System Devices Panel (CSDP) in October 2007 on its Endeavor zotarolimus-eluting stent (ZES), seeking approval for the indication of treating de novo native coronary lesions ≤27 mm with reference vessel diameters of 2.5 to 3.5 mm. The FDA asked the CSDP to determine whether the data presented demonstrated a reasonable level of safety and effectiveness, with clinical benefits clearly outweighing short- and long-term risks of ZES use. Important efficacy end points included ischemia-driven target lesion revascularization (TLR) or target vessel revascularization (TVR); safety end points included death, MI, and ST. The …