Clinical studies with paclitaxel - eluting stent systems

Coronary artery stents mechanically buttress the arterial wall and prevent negative remodeling, leading to increased lumen gain and less angiographic and clinical restenosis as compared with balloon angioplasty alone. Although stents prevent negative remodeling, they do not eliminate restenosis, as they cause complex arterial injury triggering responses that culminate in the induction of neointimal hyperplasia. For many years after the development of balloon angioplasty and stenting, many unsuccessful attempts were made to find methods to prevent neointimal hyperplasia. In 1995, Sollot and colleagues were first to recognize the ability of the antineoplastic compound paclitaxel to limit neointimal hyperplasia formation. In 1997, Axel and colleagues were the first to demonstrate that paclitaxel locally delivered locally to the arterial wall limited neointimal hyperplasia in an animal model. After success in preclinical and human trials, the FDA approved the use of paclitaxel-eluting coronary stents in 2004 on the strength of the pivotal TAXUS trials, which demonstrated that stents utilizing a polymer coating as a paclitaxel delivery vector were effective in the prevention of restenosis. Subsequent trials have confirmed the effectiveness of paclitaxel in restenosis prevention. In these trials, paclitaxel was delivered using both polymer-coated stents and stents directly impregnated with drug, and on different stent platforms by different manufacturers. Paclitaxel eluting stents have been shown to be effective in a variety of cardiovascular lesion and patient subsets in randomized trial and registry data sets. Although there are concerns that locally delivered paclitaxel and/or its polymer delivery vehicle may lead to impaired vascular healing that may predispose to the development of stent thrombosis, pooled data analyses have confirmed an acceptable safety profile for paclitaxel-eluting coronary stents. The current generation of paclitaxel eluting stents have different performance profiles shen compared to first generation and second generation coronary stents eluting sirolimus or related compounds, especially in regard to target lesion revascularization rates. However, whether these difference translates into clinically relevant benefits remains debatable. In addition, newer paclitaxel elution techniques and newer paclitaxel-eluting stent architecture may improve the performance of paclitaxel-eluting stents. As the only approved non-limus based antiproliferative agent currently available, paclitaxel is uniquely positioned in the future of interventional vascular medicine.