Paclitaxel-Eluting Stents

Abstract

In the past few years, drug-eluting stents have emerged as one of the most promising technologies in the field of interventional cardiology. Loaded with antiproliferative and anti-inflammatory agents, these stents have the potential to reduce post-stent-implantation restenosis significantly. In particular, sirolimus- and paclitaxel-eluting stents (PES) have been shown to be remarkably effective and are now available commercially in many countries.However, several PES systems have been under clinical investigation and produced different outcomes because of differences in their stent platforms, their total drug load, and their drug delivery and release concepts. The multicenter studies ASPECT (Asian Paclitaxel-Eluting Stent Clinical Trial), ELUTES (European evaLUation of PacliTaxel-Eluting Stent), and DELIVER (the RX Achieve drug-eluting coronary stent system in the treatment of patients with de novo native coronary lesions) I and II have been conducted to evaluate a PES system with direct impregnation of the agent onto the stent surface without using any further coatings. ASPECT and ELUTES revealed a clear dose response with descending binary restenosis rates for ascending drug dosages. However, statistically significant reductions of neointimal proliferation were only observed in the high-dose groups. DELIVER I, a study including 1043 patients, demonstrated the safety of the directly paclitaxel-coated RX Achieve stent, but the late loss reduction did not translate into a sufficient reduction of the clinical endpoints. The TAXUS program has been conducted to explore safety and efficacy of the TAXUS polymer-based, PES system, which delivers polymer-controlled low-dose paclitaxel, in contrast to the stents with direct impregnation. TAXUS I, a randomized trial with 61 patients, revealed the first evidence of the potential of this concept with remarkable results in safety and reduction of in-stent restenosis. In a larger patient population, the following TAXUS II trial demonstrated the safety and superior performance of the TAXUS-slow and TAXUS-moderate release stents over uncoated control stents for the reduction of restenosis up to 12 months after implantation. TAXUS IV, the pivotal US multicenter study including 1314 patients, underlined the efficacy of this stent in a wide range of complex patient and lesion subsets, including small vessels, long lesions, and diabetes mellitus. The ongoing TAXUS V and VI trials are designed to show whether this benefit will be reproducible in even more complex lesion subsets. Beside these randomized studies, several 'real-world' registries have recently been started to evaluate the performance of the TAXUS stent in daily clinical practice. Programs like these are vital to sufficiently monitor patients who have received a drug-eluting stent, particularly because of the controversy regarding long-term effects.