The following introductory and background information on the occurrence of restenosis following percutaneous coronary intervention and the role of drug-eluting stents was previously highlighted in the January 2003, Interventional Cardiology Journal Scan. Shortly following the publication of this journal scan, other relevant and interesting studies have since been published on paclitaxel-eluting stents and are featured below. |
Restenosis, the renarrowing of the lumen of the coronary artery, in the months following a successful percutaneous balloon angioplasty or stent implantation remains the main limitation to percutaneous coronary intervention (PCI). Serial intravascular ultrasound (IVUS) studies have shown that restenosis following stent deployment is due almost entirely to smooth muscle hyperplasia and matrix proliferation.
Despite intense investigation in animal models and clinical trials, most pharmacologic agents have been found to be ineffective in preventing restenosis. Although studies frequently report success in the suppression of neointimal proliferation in animal models of balloon vascular injury, to date, few of them have been successful in clinical trials.
Recent studies have proven endovascular radiation to be an effective strategy for the prevention of restenosis. Unfortunately, intracoronary brachytherapy is associated with delayed coronary endothelialization and the potential for late vascular thrombosis, and therefore requires prolonged antiplatelet therapy.
Drug-eluting stent technology has the potential to be one of interventional cardiology's greatest breakthroughs for solving the problem of restenosis. |
Recent studies (FIM, RAVEL, and SIRIUS [see trial glossary for expansion of acronyms]) have shown that sirolimus-eluting stents can significantly reduce the incidence of in-stent restenosis in de novo lesions, with very low rates of neointimal proliferation and late lumen loss, and can do so without creating edge effect or affecting plaque burden behind the struts.
In addition, studies evaluating paclitaxel-eluting stents have also shown favorable results. Paclitaxel (Taxol), derived from a novel class of anticancer agents known as taxanes, was originally developed as a chemotherapeutic agent derived from the Pacific yew tree and is the first taxane to enter clinical trials that has shown promising results in the treatment of ovarian, breast, and other cancers. Taxanes exert their cytotoxic effects through a unique mechanism by increasing the assembly of dysfunctional and extraordinarily stable microtubules. These microtubules are essential in cellular division, cell migration, intracellular signaling, and extracellular secretory processes. Therefore, paclitaxel has the ability to interfere with cell proliferation, mainly of smooth muscle cells and less of endothelial cells; migration; and inflammation and secretion of extracellular matrix -- all of which are important contributors to restenosis.
Unlike other antiproliferative agents, paclitaxel has several characteristics that make it a good candidate for local drug therapy for the inhibition of smooth muscle cell proliferation and restenosis after percutaneous interventions. It is highly lipophilic and thus promotes rapid cellular uptake and has a long-lasting effect in the cell, even after brief, single-dose applications at very low concentrations. Local paclitaxel delivery via a double balloon after experimental angioplasty in an animal model of restenosis has shown a reduction in neointimal stenosis without interfering with normal re-endothelialization.