Sirolimus eluting stent: a new era in interventional cardiology?

Coronary artery stents have emerged as the preferred tool for percutaneous coronary interventions during the past decade by eliminating abrupt vessel closure and reducing restenosis compared with balloon angioplasty. While coronary artery stents prevent constrictive arterial remodeling and elastic recoil, the implantation is associated with more severe arterial vascular injury than balloon angioplasty alone. The arterial injury initiates a vasculoproliferative response with smooth muscle cell proliferation and migration as well as extracellular matrix formation, which may lead to severe neointimal hyperplasia with in-stent restenosis in 10-30% of cases. Sirolimus, a naturally occurring macrocyclic lactone, has been identified as a pharmacological cell cycle inhibitor with potent antiproliferative and antimigratory effects on vascular smooth muscle cells in vitro. The systemic administration of sirolimus has been shown to effectively reduce neointimal hyperplasia in experimental restenosis models. Subsequently, sirolimus has been incorporated at therapeutically important doses into biocompatible polymers, which made it suitable for stent-based drug elution. Investigation of sirolimus eluting stents in both experimental and clinical restenosis studies have demonstrated dramatic reductions in neointimal hyperplasia. Accordingly, sirolimus eluting stents offer an attractive mode of local drug delivery by minimizing systemic toxicity and maximizing local dose requirements. In addition, sirolimus eluting stents hold great promise to effectively prevent restenosis.