Novel approaches to reduce restenosis

Abstract

Percutaneous coronary intervention (PCI) has become the major technique of revascularization and is replacing cardiac bypass surgery. PCI is typically performed today with a combination of balloon dilatation and stents, with some 80% of the procedures followed by stent implantation. After balloon dilatation, an acute recoil response can be responsible for some 30% immediate loss of the vessel lumen at the end of the procedure. Restenosis is the late loss (within 6-9 months) of the lumen of the artery due to vessel shrinkage (negative remodeling) and an intense proliferative response to the local injury. Stents reduce restenosis by 30% by preventing acute recoil and reducing long-term negative arterial remodeling. Yet, long-term pressure of the stent struts against the vessel wall stimulates an increased arterial proliferative response, which is the major cause for stent restenosis. Limiting the proliferative response by local radiation (brachytherapy) have reduced restenosis, at a cost of increased late thrombogenicity and delayed vessel healing. Drug-eluting stents have shown extremely promising results in limiting restenosis. Rapamycin and paclitaxel are the major drugs in eluting stents in clinical use today, having reduced restenosis to less than 10%. Local cellular and genetic therapy approaches are currently at preclinical phases. The future of percutaneous revascularization remains bright and will enhance the effectiveness of PCI as the primary revascularization therapy for coronary artery disease.