title: Perspectives of drug-eluting stents: the next revolution.
abstract: Coronary stent implantation has become a well established therapy in the management of coronary artery disease (CAD). Although the Stent Restenosis Study (STRESS) and Belgium-Netherlands Stent (BENESTENT) trials demonstrated convincingly that stenting is superior to percutaneous transluminal coronary angioplasty with respect to restenosis in de novo lesions, there is, however, still a high incidence (10 to 50%) of restenosis following stent implantation. Improvements in stent design and implantation techniques resulted in an increase in the use of coronary stents and today, in most centers in the US and Europe, stenting has become the predominant form of nonsurgical revascularization accounting for about 80% of all percutaneous coronary intervention procedures. Coronary stents provide luminal scaffolding that virtually eliminates elastic recoil and remodelling. Stents, however, do not decrease neointimal hyperplasia and in fact lead to an increase in the proliferative comportment of restenosis. Agents that inhibit cell-cycle progression indirectly have also been tested as inhibitors of vascular proliferation. When coated onto stents, sirolimus, a macrolide antibiotic with immunosuppressive properties, and paclitaxel and dactinomycin, both chemotherapeutic agents, induced cell-cycle arrest in smooth muscle cells (SMC) and inhibited neointimal formation in animal models. Preliminary clinical studies with drug-eluting stents produced dramatic results eliminating restenosis in large and mid-size arteries. Quantitative coronary angiography and intravascular ultrasound demonstrated virtually complete inhibition of tissue growth at 6 and 12 months after sirolimus-eluting stent implantation. Results are also very encouraging with paclitaxel-coated stents. However, it needs to be proven that current drug-eluting stents will produce similar results in 'real life' interventional practice (long lesions, lesions in small vessels, in vein grafts, chronic total occlusions, and bifurcated and ostial lesions). The ongoing randomized, double-blind sirolimus-coated Bx Velocity trade mark balloon expandable stent in the treatment of patients with de novo coronary artery lesions (SIRIUS) trial may answer some of these concerns. With further improvements, including the expansion of drug-loading capacity, double coatings and coatings with programmable pharmacokinetic capacity using advances in nanotechnology (which may allow for more precise and controlled release of less toxic and improved molecules), we think that in the next few years the practice of interventional cardiology may undergo major changes. A new era of dramatic improvements in the treatment of CAD may have dawned. The prospect of approval of this technology should herald a host of clinical trials to revisit basic assumptions about the place of coronary stenting in the contemporary care of obstructive (and nonobstructive) CAD.
authors.affiliation: Lenox Hill Heart and Vascular Institute of New York and Cardiovascular Research Foundation, New York, New York 10021, USA. jmoses@lenoxhill.net
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Moses
authors.forename: Nicholas
authors.initials: N
authors.lastname: Kipshidze
authors.forename: Martin B
authors.initials: MB
authors.lastname: Leon
mesh_terms: D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D023903:Coronary Restenosis / Q000209:etiology / Q000517:prevention & control; D003609:Dactinomycin / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D017239:Paclitaxel / Q000008:administration & dosage / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D020123:Sirolimus / Q000008:administration & dosage / Q000627:therapeutic use; D015607:Stents / Q000009:adverse effects / Q000639:trends*
chemical_list: D000970:Antineoplastic Agents; D003609:Dactinomycin; D017239:Paclitaxel; D020123:Sirolimus