Coated Stents for the Prevention of Restenosis: Part II

Abstract

T his is the second part of a 2-part article that reviews the literature on coated stents and their effects on in-stent restenosis after percutaneous coronary intervention (PCI). Part I of this review discussed the pathophysiology of in-stent restenosis, specific stent coatings, and animal studies investigating coated stents. Part II discusses nonrandomized studies and clinical trials in humans. Studies in humans have examined stents coated with biocompatible materials and drug-eluting stents. Complications and controversies associated with this new technology are also addressed. Human StudiesThe risk of developing in-stent restenosis is related to a variety of factors, both clinical and procedural. [1][2][3][4][5][6][7] On the basis of these risk factors, patients enrolled in both nonrandomized studies and clinical trials have been classified as having a high, intermediate, or low risk of restenosis. Therefore, the binary restenosis rates (Ͼ50% diameter stenosis angiographically) and major adverse cardiac event (MACE) rates in human studies vary greatly depending on the overall risk profile of patients enrolled in these studies. Non-Randomized Studies Stents Coated with Biocompatible MaterialsThe biocompatibility of stents coated with several materials, including carbon, gold, silicon carbide, and phosphorylcholine, has been investigated in humans. The Carbostent (Sorin Biomedica Cardio) is a metal stent coated with a carbon film that is thought to be less thrombogenic than uncoated steel stents. 8 Antoniucci et al 9 investigated the long-term biocompatibility of the Carbostent in a group of 112 patients with an intermediate risk of developing restenosis. Six-month follow-up revealed low MACE and restenosis rates of 12% and 11%, respectively. A second study in another group of 112 patients at high risk for restenosis resulted in a MACE rate of 20% and a binary restenosis rate of 25% by 6 months. 10 These results suggest that the Carbostent is well tolerated in vivo and possibly inhibits neointimal hyperplasia, especially in high-risk patients (Table 1).Gold has been touted as a biocompatible material and has been thought to be ideal for coating coronary stents because of its radio-opaque properties. 1 Two studies evaluating the biocompatibility of gold-coated stents suggested equivalency with uncoated steel stents. 11,12 However, two other studies concluded that these stents may increase neointimal hyperplasia compared with uncoated stents, although patients at a higher risk for restenosis were enrolled. 13,14 Follow-up angiography at 6 months demonstrated a relatively high lumen late loss (postintervention minimum luminal diameter minus the minimum luminal diameter at follow-up) and diameter stenosis in both studies (Table 1). Overall, there have been conflicting results in observational studies examining goldcoated stents, and the restenosis rates seem to be no better than those obtained with uncoated steel stents.Silicon carbide is an inert semiconductor that can be coated onto prosthetic surfaces and has be...

Unique, Highly Proliferative Growth Phenotype Expressed by Embryonic and Neointimal Smooth Muscle Cells Is Driven by Constitutive Akt, mTOR, and p70S6K Signaling and Is Actively Repressed by PTEN

“…Recently, an increasing number of animal and human studies have shown significant reductions in intimal thickening associated with attenuated PI3K/Akt/mTOR/p70S6K signaling after rapamycin treatment. [21][22][23][24][25][26][27][28] Two-year follow-up studies in humans have shown persistent inhibition of in-stent restenosis with few, if any, adverse effects, which demonstrates the effectiveness and safety of rapamycin. 27,28 Our studies show the high proliferative capability, even under serum-deprived conditions, exhibited by both embryonic and neointimal SMCs is dependent on low PTEN activity resulting in constitutive Akt-dependent Figure 5.…”

“…[21][22][23] Most approaches to limit the rate of restenosis, designed to target factors that stimulate growth of traditional adult-derived serum-dependent SMCs, 16,17,21 have been largely unsuccessful. Recently, an increasing number of animal and human studies have shown significant reductions in intimal thickening associated with attenuated PI3K/Akt/mTOR/p70S6K signaling after rapamycin treatment.…”

RAGE Axis

“…56 Taken together, these considerations underscore the complexity of these model systems and suggest that preclinical testing of novel therapeutic targets in restenosis ultimately requires the use of species such as pigs, rabbits, or nonhuman primates before testing in human subjects. 57,58 …”

One-Year Clinical Results With the Slow-Release, Polymer-Based, Paclitaxel-Eluting TAXUS Stent

“…The polymer-regulated delivery of both paclitaxel and sirolimus at the site of arterial injury has been shown to reduce clinical and angiographic restenosis rates after stent implantation in de novo coronary lesions. [1][2][3][4][5][6][7] Specifically, in the pivotal TAXUS-IV trial, slow-release paclitaxel-elution from the TAXUS stent resulted in lower 9-month rates of target-lesion revascularization (TLR), target-vessel revascularization (TVR), and binary restenosis than bare-metal control stents. 7 Longer-term follow-up from this trial has not been reported, nor have clinical TLR rates been examined in subgroups known to affect restenosis.…”