Drug-Eluting Stent Update 2007

Abstract

Received May 14, 2006; January 26, 2007. Analyst projections for the drug-eluting stent (DES) market estimated that the total number of DES implanted in 2010 would go beyond 4.5 million worldwide. Although the initial results seemed promising, longer-term follow-up in a broader range of patients revealed some pitfalls. Delayed neointimal growth, enhanced platelet aggregation, a local hypersensitivity reaction against the polymer coating, stent fracture, and a failure of sirolimus-, paclitaxel-, and tacrolimus-eluting stents to reduce neointimal hyperplasia at 90 and 180 days in animals, when the drug was completely eluted from the stent, are just several examples.1–8 The number of stents currently under investigation is substantial. They are all loaded with drugs that interfere with pathways in the process of inflammation and neointimal proliferation. However, the process of restenosis is a sequence of complex events that has been only partly elucidated over the last 2 decades.9 Locally acting DES provide the opportunity to interfere with the various mechanisms responsible for each step in the restenotic cascade, and a wide variety of different agents are currently available. Although only sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES) have received US Food and Drug Administration (FDA) approval to date, multiple alternative devices are attempting to find their way to achieve the same goal, namely a reduction of restenosis and the need for repeat interventions. Six Limus family–related drugs are currently being studied in DES, namely sirolimus, everolimus, biolimus A9, zotarolimus, tacrolimus, and pimecrolimus. Sirolimus, everolimus, biolimus A9, and zotarolimus all bind to the FKBP12 binding protein, which subsequently binds to the mammalian target of rapamycin (mTOR) and thereby blocks the cell cycle mainly of the smooth muscle cell from the G1 to S phase. The mechanisms of action of tacrolimus and pimecrolimus are different. Both drugs bind to FKBP506. The tacrolimus/pimecrolimus …