ABSTRACT
Although stenting has significantly reduced restenosis as compared to balloon angioplasty, the unacceptably high incidence of in-stent restenosis has led to the development of drug-eluting stents (DES). There has been a growing expectation among many interventional cardiologists that DES will conquer the problem of in-stent restenosis. Initial results from clinical trials in ideal coronary lesions have shown a significant reduction in the frequency of restenosis at 6 and 12 months. In the largest trials to date, restenosis rates have ranged from 0% to 9% for sirolimus eluting BX Velocity stents compared to 26-34% in uncoated BX Velocity stents (Leon, M. published data).1 Similarly, paclitaxel eluting stents (TAXUS trials I and II) have also shown promising results at 6 and 12 months with restenosis rates of 2-5% versus 19% in control stents (Colombo, A. Unpublished data).2 However, these studies have yet to adequately address many complex ‘real-world’ lesion subsets (e.g. diffuse disease, bifurcations, ostial lesions, saphenous vein bypass grafts, and stenting of thrombus containing lesions in acute coronary syndromes). Early results of studies conducted of more complicated lesion morphologies suggest that restenosis may be reduced but is certainly not eliminated.3-5
MECHANISM OF RESTENOSIS
In balloon angioplasty, the major component of the restenosis process is constrictive negative remodeling (collagen synthesis and cross-linking occurring within the plaque and/or the adventitia) rather than neointimal thickening.6 Conversely, in-stent restenosis occurs solely as a result of excessive neointimal growth consisting predominantly of extracellular matrix and smooth muscle cells.7 In-stent neointimal growth is governed by the extent of vessel wall injury, platelet deposition, and the induction of inflammation; these processes are regulated by chemotactic factors, inflammatory cytokines, growth factors, and mitotic signals that lead to smooth muscle migration and proliferation.8 In human stented arteries, neointimal formation is proportional to the circumferential medial
*The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense.
