A polymer coated cicaprost-eluting stent increases neointima formation and impairs vessel function in the rabbit iliac artery

Drug-eluting stents have been successful in reducing in-stent restenosis but are not suitable for all lesion types and have been implicated in causing late stent thrombosis due to incomplete regeneration of the endothelial cell layer. In this study we implanted stents coated with cicaprost, a prostacyclin analogue with a long plasma half-life and antiproliferative effects on vascular smooth muscle cells, into the iliac arteries of rabbits. At 28-day follow-up we compared neointima formation within the stented vessels and vascular function in adjacent vessels, to assess if cicaprost could reduce restenosis without impairing vessel function. Arteries implanted with cicaprost eluting stents had significantly more neointima compared to bare metal stents. In adjacent segments of artery, endothelium-dependent relaxation was impaired by the cicaprost-eluting stent but vasodilation to an endothelium-independent vasodilator was maintained. We conclude that the presence of the polymer and sub-optimal release of cicaprost from the stent may be responsible for the increased neointma and impaired functional recovery of the endothelium observed. Further experiments should be aimed at optimising release of cicaprost and exploring different stent polymer coatings

Implantation of paclitaxel-eluting stents in saphenous vein grafts: clinical and angiographic follow-up results from a multicentre study.

Objective: To define the clinical and angiographic follow-up results after implantation of paclitaxel-eluting stents (PESs) in stenotic saphenous vein grafts (SVGs). Design: Prospective multicentre study. Comparison with a control group. Methods: 60 consecutive patients with 65 lesions located in 65 SVGs (mean (SD) age of vein grafts 11.3 (5.7) years) treated with PES (V-Flex Plus, 2.7 mg/mm2 paclitaxel, Cook) and 60 patients with 60 SVG lesions treated with bare metal stent (BMS) were included. Lesions had to be ,20 mm in length and in grafts of 2.75–3.5 mm diameter. The 6 month angiographic follow-up was obtained on 51 lesions (79%) of the PES group and on 51 lesions (85%) of the BMS group. Results: Baseline clinical and angiographic characteristics were comparable between both groups. At angiographic follow-up, three vein grafts in the PES group and five vein grafts in the BMS group were occluded. In-stent late lumen loss was lower in PES than in BMS (0.61 (0.81) vs 1.06 (0.72) mm, respectively; p = 0.021). In-stent binary restenosis rates were 12% vs 33%, respectively, (p = 0.012). Linear regression analysis showed BMS to be the only factor with an effect on late lumen loss (p = 0.011). Target-vessel failure rates were 18% in the PES group and 41% in the BMS group (p = 0.019), whereas major adverse cardiac event (MACE) rates at 180 days were 15% and 37%, respectively (p = 0.014). Conclusions: Implantation of non-polymer-based PES in SVG lesions is associated with a lower late lumen loss and restenosis rate than those of BMS. There remains a substantial target-vessel failure rate and MACE rate even at 6 months owing to graft occlusion or new lesions in the graft

A polymer coated cicaprost-eluting stent increases neointima formation and impairs vessel function in the rabbit iliac artery

Drug-eluting stents have been successful in reducing in-stent restenosis but are not suitable for all lesion types and have been implicated in causing late stent thrombosis due to incomplete regeneration of the endothelial cell layer. In this study we implanted stents coated with cicaprost, a prostacyclin analogue with a long plasma half-life and antiproliferative effects on vascular smooth muscle cells, into the iliac arteries of rabbits. At 28 day follow-up we compared neointima formation within the stented vessels and vascular function in adjacent vessels, to assess if cicaprost could reduce restenosis without impairing vessel function. Arteries implanted with cicaprost eluting stents had significantly more neointima compared to bare metal stents. In adjacent segments of artery, endothelium-dependent relaxation was impaired by the cicaprost-eluting stent but vasodilation to an endothelium-independent vasodilator was maintained. We conclude that the presence of the polymer and sub-optimal release of cicaprost from the stent may be responsible for the increased neointma and impaired functional recovery of the endothelium observed. Further experiments should be aimed at optimising release of cicaprost and exploring different stent polymer coatings

Sirolimus-eluting coronary stents: a review

The sirolimus-eluting coronary stent received CE Mark approval in Europe in April 2002. In the US, FDA approval followed in April 2003. Since the preliminary results from the First-in-Man feasibility study were presented, several randomized, controlled trials have documented the profound antiproliferative effects of sirolimus, a macrolide antibiotic and potent cytostatic inhibitor of smooth muscle cell proliferation. Subsequently, the body of clinical evidence was increased by the second wave of evidence from trials in more complex lesions (such as in-stent restenosis, small vessels, chronic total occlusions) and “high-risk” patients such as those with diabetes. More recently we have had the opportunity to compare the two commercially available drug-eluting stents following the presentation of data from six head-to-head trials. As a result of numerous single and multi-center, national and international studies in which the safety and efficacy of sirolimus-eluting coronary stents have been subjected to close scrutiny, the global interventional cardiology community now has a wealth of evidence in support of the use of this technology resulting in dramatically improved patient outcomes after percutaneous intervention

Evaluation of the efficacy and long-term safety outcomes of first generation drug-eluting stents in off-label indications

FDA approval of drug-eluting stents (DES) in 2002, was based on data obtained from several pivotal, short-term (< one year) randomized control trials that evaluated their efficacy in reducing in-stent restenosis when used in treatment of coronary artery lesions compared with bare metal stents (BMS). These trials excluded patients with complex coronary lesions. When the FDA approved use of DES in treatment of coronary artery lesions, the on-label indications only applied to a very limited subset of simple lesions. Immediate advantages of DES were observed in clinical practice for on-label indications, specifically in their ability to significantly reduce in-stent restenosis after PCI. The increased short-term safety and efficacy seen in on-label clinical cases soon led clinicians to expand the use DES to more complex lesions. These complex indications, not included in the pivotal FDA trials, are considered off-label. Off-label indications include bifurcation lesions, ostial lesions, lesions greater in length and diameter than those approved by the FDA, implantation in saphenous vein grafts, and lesions in the left main coronary artery. Currently, DES use for treatment of lesions presenting off-label indications may comprise as much as 60% of clinical cases. However, early evidence that DES may play a role in adverse safety outcomes, has led many to question the use of DES outside their on-label indications. This paper sought to evaluate some of the current research investigating first generation DES use in four different off-label indications: coronary artery bypass graft lesions, saphenous vein graft lesions, ostial lesions, and chronic total coronary occlusions. In particular, it looked at studies, which compared the efficacy and clinical outcomes of DES and BMS treatment of each of the different lesion types. The results of this evaluation were very promising in that of the four specific off-label indications evaluated, all of them showed to be superior in reduction of neointimal growth and subsequent in-stent restenosis. Additionally, DES treatment of left main coronary artery lesions, saphenous vein graft lesions, and chronic total coronary occlusions showed to be superior in reducing the incidence rate of major adverse cardiac events and target vessel revascularization over various follow-up durations. The only scenario that DES did not prove to be superior to BMSs was the treatment of ostial lesions. Long-term randomized control trials with large study populations should be performed to further elucidate the effects of DES treatment of specific off-label lesions

Bare-metal stents versus drug-eluting stents in large (≥3.5mm) single coronary artery: Angiographic and clinical outcomes at 6 months

SummaryBackgroundAlthough drug-eluting stents (DES) have been shown to dramatically reduce restenosis and improve the rate of event-free survival in large randomized trials, the benefit of DES appears to be limited to restenosis. In large arteries, it is not clear which type of stent is more superior in angiographic and clinical outcomes between DES and bare-metal stents (BMS). We compared the angiographic and clinical outcomes of DES versus BMS in large arteries (≥3.5mm).MethodTwo hundred and forty patients from March 2002 to March 2007 received stents; 196 patients were treated with DES (44.9% sirolimus-eluting stents; 43.9% paclitaxel-eluting stents; 11.2% zotarolimus-eluting stents) and 44 with cobalt–chromium BMS for single de novo lesions in a large vessel. All subjects received aspirin, clopidogrel, and/or cilostazol as the standard antiplatelet regimen. The angiographic and clinical outcomes were evaluated at 6 months.ResultsFor the baseline characteristics, there were no significant differences between the DES and BMS groups. In addition, for the initially implanted stent there was no difference in the length, stent diameter, and lesion site between the two groups. After 6 months, the follow-up angiogram showed that in-stent diameter restenosis and late loss was more common with BMS than DES (39±21% vs. 19±17%, p=0.007; 1.44±0.83mm vs. 0.62±0.58mm, p=0.009, respectively). However, the target-lesion revascularization/target-vessel revascularization, and total major adverse cardiac events showed no significant differences between the groups (5.3% vs. 3.6%, p=0.62; 5.3% vs. 4.6%, p=0.86, respectively).ConclusionThe DES and cobalt–chromium BMS placed in large coronary arteries showed equally favorable 6-month clinical outcomes, although the 6-month angiographic results appeared more favorable in the DES group than in the BMS group