Stent Control Group Research Articles

EW-7197 eluting nano-fiber covered self-expandable metallic stent to prevent granulation tissue formation in a canine urethral model

PurposeTo evaluate an EW-7197-eluting nanofiber-covered stent (NFCS) for suppressing granulation tissue formation after stent placement in a canine urethral model.Materials and methodsAll experiments were approved by the committee of animal research. A total of 12 NFCSs were placed in the proximal and distal urethras of six dogs. Dogs were divided into two groups with 3 dogs each. The control stent (CS) group received NFCSs and the drug stent (DS) group received EW-7197 (1000 μg)-eluting NFCSs. All dogs were sacrificed 8 weeks after stent placement Histologic findings of the stented urethra were compared using the Mann-Whitney U test.ResultsStent placement was technically successful in all dogs without procedure-related complications. On urethrographic analysis, the mean luminal diameter was significantly larger in the DS group than in the CS group at 4 and 8 weeks after stent placement (all p < 0.001). On histological examination, mean thicknesses of the papillary projection, thickness of submucosal fibrosis, number of epithelial layers, and degree of collagen deposition were significantly lower in the DS group than in the CS group (all p < 0.001), whereas the mean degree of inflammatory cell infiltration was not significantly different (p > 0.05).ConclusionThe EW-7197-eluting NFCS is effective and safe for suppressing granulation tissue formation after stent placement in a canine urethral model.

Mesh-covered embolic protection stent implantation in ST-segment-elevation myocardial infarction: final 1-year clinical and angiographic results from the MGUARD for acute ST elevation reperfusion trial.

The MGuard, a bare metal stent covered with a polymer mesh, was designed to reduce distal embolization during percutaneous coronary intervention in ST-segment-elevation myocardial infarction. In the MGUARD for Acute ST Elevation Reperfusion trial, the primary end point of complete ST-segment resolution was significantly improved with the MGuard compared with control. We evaluated 1-year clinical and angiographic results. Patients with ST-segment-elevation myocardial infarction ≤12 hours undergoing primary percutaneous coronary intervention of a single de novo native lesion were randomized to the MGuard versus any commercially available metallic stent (39.8% drug-eluting). Clinical follow-up was performed through 1 year, and angiography at 13 months was planned in 50 MGuard patients. There was no difference in major adverse cardiac events (1.8% versus 2.3%; P=0.75) at 30 days between the groups. Major adverse cardiac events at 1 year were higher with the MGuard, driven by greater ischemia-driven target lesion revascularization (8.6% versus 0.9%; P=0.0003). Conversely, mortality tended to be lower with the MGuard at 30 days (0% versus 1.9%; P=0.04) and at 1 year (1.0% versus 3.3%; P=0.09). Late lumen loss at 13 months in the MGuard was 0.99±0.80 mm, and binary restenosis was 31.6%. In patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention, a trend toward reduced 1-year mortality was present in patients treated with the MGuard stent. Target lesion revascularization and major adverse cardiac events rates during follow-up were higher in the MGuard group than in the control stent group, and angiographic late loss of the MGuard was consistent with that expected from bare metal stents. http://www.clinicaltrials.gov. Unique identifier: NCT01368471.

Efficacy of the S.M.A.R.T. Control vs. Other Stents for Aortoiliac Occlusive Disease in Contemporary Clinical Practice

To compare the safety and efficacy of the S.M.A.R.T. Control stent vs. other stents in patients with symptomatic aortoiliac occlusive disease (AIOD) followed for up to 4 years. A subgroup analysis of data from a retrospective multicenter registry examined 2036 symptomatic patients (1659 men; mean age 71±8 years) who received stent-supported endovascular therapy for 2541 AIOD lesions between April 2005 and December 2009. The cohort was divided into the S.M.A.R.T. stent group (955 patients/1196 lesions) and the "other" stent group (1081 patients/1345 lesions). The main study outcomes of primary patency and event-free survival at 4 years were compared before and after propensity matching analysis. The rates for freedom from major amputation, surgical conversion, target lesion revascularization (TLR), and major adverse limb events were also assessed. The S.M.A.R.T. Control stent group had greater frequency of critical limb ischemia (CLI), TASC C/D lesions, and chronic total occlusions. The mean follow-up was 25±17 months in the S.M.A.R.T. group vs. 29±19 months in the other stent group. After propensity matching, 4-year primary patency (86% vs. 76%, p<0.001) and freedom from adverse limb events (93% vs. 90%, p=0.04) were greater in the S.M.A.R.T. Control stent group, while event-free survival rates (75% vs. 77%, p=0.50) were similar between groups. Univariate subgroup analysis showed that use of the S.M.A.R.T. stent was associated with greater primary patency in patients with renal insufficiency (serum creatinine >1.5 mg/dL) and CLI. After propensity matching analysis, the durability of the S.M.A.R.T. stent was superior to that of other stents, which might reflect differing design characteristics.

876 Anti-proliferative and anti-inflammatory effects of Ramiprilat-coated stent in a porcine coronary overstretch restenosis model

Background: The angiotensin-converting enzyme inhibitor ramiprilat has been previously demonstrated to protect myocardium from ischemia/reperfusion injury. Objectives: The aim of this study was to examine the anti-proliferative and anti-inflammatory effects of ramiprilat-coated stent in a porcine coronary overstretch restenosis model. Methods: Pigs were randomized into two groups in which the coronary arteries (16 pigs, 16 coronaries in each group) had either a ramiprilat-coated MAC stent or control MAC stent (AMG, Munich, Germany). Stents were deployed with oversizing (stent/artery ratio 1.3:1) in porcine coronary arteries, and histopathologic analysis was assessed at 28 days after stenting. Results: There were no significant differences in the neointima area normalized to injury score and inflammation score between the two groups (1.58 ± 0.43, 1.60 ± 0.39 in ramiprilat stent group vs. 1.60 ± 0.57, 1.62 ± 0.49 in control stent group, respectively). In neointima, most inflammatory cells were lymphohistiocytes. Overall, significant positive correlations were found between the lymphohistiocyte count and the neointima area (r = 0.567, p < 0.001) and between the lymphohistiocyte count and the percent area stenosis (r = 0.478, p < 0.001). Although lymphohistiocyte count (170 ± 121 cells vs. 162 ± 83 cells) and fibrin scores (0.15 ± 0.06 vs. 0.17 ± 0.07, p = 0.8) were not different between both groups, there was a strong trend of smaller neointima area (1.06 ± 0.51 mm2 vs. 1.28 ± 0.35 mm2, p = 0.083) and percent area stenosis (18.9 ± 8.7% vs. 22.8 ± 7.2%, p = 0.088) in the ramiprilat stent group compared with control group. Conclusions: Ramiprilat-coated stent showed a trend of more inhibitory effects on neointimal hyperplasia without differences in effects on inflammatory cell infiltration and arterial healing compared with control stent in a porcine coronary restenosis model.

Effect of a Dual Drug-Coated Stent With Abciximab and Alpha-Lipoic Acid in a Porcine Coronary Restenosis Model

Background and ObjectivesThe aim of this study was to examine the anti-proliferative and anti-inflammatory effects of a stent coated with abciximab and alpha-lipoic acid (ALA) in a porcine coronary overstretch restenosis model.Materials and MethodsA total of 10 pigs were randomized into two groups (10 pigs, 10 coronaries in each group) in which the coronary arteries were stented with a dual-coated stent and a bare metal stent (control) by randomization. Stents were deployed with oversizing (stent/artery ratio 1.3 : 1) in the porcine coronary arteries, and histopathology was assessed 28 days after stenting.ResultsThere was no significant difference in the injury score between the two groups. In the neointima, the lymphohistiocyte count was significantly lower in dual-coat stent group compared with the control stent group (120±85 cells vs. 159±80 cells, p=0.048). There was no significant difference in the fibrin score between the two groups (0.16±0.34 in the dual-coated stent group vs. 0.25±0.48 in the control stent group, p=0.446). The neointima area was not significantly different between both groups (1.55±0.8 mm2 in dual-coated stent group vs. 1.40±0.86 mm2 in the control stent group, p=0.447).ConclusionAlthough the dual-coated stent with abciximab and ALA showed no significant difference in inhibition of neointimal hyperplasia when compared with the bare metal stent, it was associated with a reduced inflammatory reaction when compared with the control stent in a porcine coronary restenosis model.

Two-Year Clinical Outcome after Carvedilol-Loaded Stent Implantation in Patients with Coronary Artery Disease

Background/AimsCarvedilol is an antioxidant that inhibits smooth muscle cell proliferation and migration. The aim of this study was to investigate the beneficial effects of carvedilol-loaded stents on 2-year clinical outcomes after stent implantation in patients with coronary artery disease.MethodsWe performed a prospective trial with male subjects to compare the safety and effects of carvedilol-loaded BiodivYsio® stents implanted into 20 patients with those of bare-metal BiodivYsio® stents implanted into 21 patients for de novo coronary lesions. The primary end point was the degree of neointimal hyperplasia, which was measured by intravascular ultrasound (IVUS) 6 months after the procedure; the secondary end point was major adverse cardiac events (MACE) at 2 years after implantation. All carvedilol and control stents were deployed successfully.ResultsA 2-year follow-up was completed for 19 patients (95%) in the carvedilol stent group and 20 patients (95%) in the control stent group. IVUS showed a trend toward a larger luminal area (6.86 ± 2.59 vs. 5.47 ± 1.52 mm2, p = 0.267), smaller neointimal area (1.34 ± 0.70 vs. 2.40 ± 1.73 mm2, p = 0.18), and reduced net decrease in luminal area (-0.78 ± 0.97 vs. -1.89 ± 1.78 mm2, p = 0.106) in the carvedilol stent group compared with the control stent group, respectively. There were no significant differences in the incidence of MACE (10.5 vs. 30.0%, respectively, p = 0.132) between the groups at 2 years after stent implantation. Stent thrombosis did not occur in either group after 2 years.ConclusionsThe carvedilol-loaded stents tended to inhibit neointimal hyperplasia without the occurrence of cardiac death, myocardial infarction, or stent thrombosis at 2-year follow-up.

Two-Year Clinical Outcome After Abciximab-Coated Stent Implantation in Patients With Coronary Artery Disease

Despite abciximab-coated stents having an inhibitory effect on coronary artery restenosis, the medium-term clinical outcome is unknown. This prospective, randomized study compared the effects of the abciximab-coated stent, which was implanted in 95 patients, with those of control bare metal stents (BMS) implanted in 93 patients for de novo coronary lesions. Stent implantation was performed without any complications associated with the procedure. The 6-month intravascular ultrasound analysis showed that the area of neointimal hyperplasia was significantly smaller in the abciximab-coated stent group compared with the control stent group (+2.0+/-1.6 mm(2) vs +3.4+/-1.7 mm(2), P=0.001). However, at 2-year clinical follow up, there were no statistically significant differences in the incidences of total major adverse cardiac events (16% vs 24%, P=0.19) and cardiac death (0% vs 1.1%, P=0.3), target vessel revascularization (16% vs 21%, P=0.4) or non-fatal myocardial infarction (0% vs 2.3%, P=0.16) in the abciximab-coated stent group compared with the control stent group. Although abciximab-coated stents are safe and inhibit neointimal hyperplasia, they have no superiority over BMS in 2-year clinical outcome.

Abstract 3444: The Effect of Alpha Lipoic Acid on Porcine Coronary Stent Restenosis

Objective: We evaluated the ability of alpha lipoic acid (ALA) to affect on coronary instent restenosis (ISR) in a porcine model. Methods: In vitro experiment: We stimulated porcine VSMC using G-CSF in the presence or absence of ALA. Activation of Akt, vascular endothelial growth factor (VEGF), extracellular signal-regulated kinase (ERK) and signal transducer and activator of transcription (STAT)-3 were determined using western blot. And also, cell proliferation and migration assay were determined. In vivo experiment:Balloon overdilation injuries were performed in 2 coronary arteries in 12 pigs. Four weeks after the balloon overdilation injury, 24 bare metal stents were placed for 24 injured coronary arteries. We randomized into two groups (12 stents per group; control group: aspirin and clopidogrel only, ALA group: aspirin and clopidogrel plus 100 mg/kg ALA during 4 weeks). 16 bare metal stents were implanted randomized two coronary arteries in 8 pigs. Group I was control stent group (n=8), Group II was ALA coated stent group (n=8). Follow-up coronary angiogram (CAG) and histopathologic assessment were performed at 4 weeks after stenting. Results: G-CSF increased the phosphorylation of ERK and STAT-3, but after pretreatment of ALA, the phosphorylation of ERK and STAT-3 were significantly reduced. On histopathologic analysis, injury score, internal elastic lamina(IEL) area did not differ significantly between the two groups. The neointimal area was 7.3±0.9 mm2 in control group and 2.2±1.1 mm2 in ALA group (p&lt;0.001), and the histopathologic area of stenosis(AS) was 75.9±8.5 % in control group, 23.5±10.5 % in ALA group (p&lt;0.001). The injury score and IEL area were not significantly different between the two groups. The neointimal area was 7.4±1.1 mm2 in control group and 1.4±0.8 mm2 in ALA group (p&lt;0.001), and the AS was 77.6±10.9 % in control group, 15.6±7.6 % in ALA group (p&lt;0.001). The number of inflammatory cells within neointima was lower in ALA group (63.2±23.7 % vs. 17.6±11.6 %, p&lt;0.001). Conclusion: ALA inhibits the activation of ERK, STAT-3 and proliferation of VSMC. Both high dose of oral ALA and ALA coated stents inhibit neointimal hyperplasia in a porcine ISR model

Influence of a Paclitaxel-Eluting Covered Metallic Stent On Tissue Hyperplasia: An Experimental Study in a Canine Biliary Model

Aim: The aim was to evaluate safety of a paclitaxel-eluting covered metallic stent in a canine biliary model by comparing histologic tissue reaction. Methods: Six paclitaxel-eluting covered metallic stents were endoscopically placed in the bile ducts of six mongrel dogs, and five covered metallic stents were placed in five dogs as controls. The dogs were sacrificed at six weeks after stent placement and gross and histopathologic examinations were done. Degree of inflammation was graded as follows: 0, none; 1, mild; 2, moderate; 3, severe. Results: All 11 dogs survived until the sacrifice without evidence of jaundice. All the stents except for two drug-eluting stents were placed within the canine bile duct successfully. Two malpositioned stents were excluded from histologic analysis. There was no migration or perforation. In the control stent group, there was no tissue ingrowth. Both proximal and distal ends of all the control stents showed minimal tissue overgrowth except for distal end obstruction in one and 20% narrowing of proximal end in another. In the drug-eluting stent group, tissue ingrowth was found in three animals. Two were malpositioned stents. Minimal tissue overgrowth was noted in both ends of three animals. One dog without malpositioned stent showed ingrowth at both ends. Microscopic examination demonstrated increased thickness of epithelial layers in middle and distal ends of canine bile ducts in contact with drug-eluting stents (575.00 ± 301.39 μm vs. 180.00 ± 109.55 μm, P = 0.022; 1150.00 ± 100.00 μm vs. 430.00 ± 323.27 μm, P = 0.012, respectively). Proximal ends of bile ducts showed no significant difference in thickness of epithelial layers, but there was tendency for increased thickness in the drug-eluting stent group (800.00 ± 282.84 μm vs. 530.00 ± 272.95 μm, P = 0.260). Canine bile duct in contact with drug-eluting stents showed less severe inflammatory reaction in the proximal and distal ends (2 vs. 2.80 ± 0.45, P = 0.024; 1.50 ± 0.58 vs. 2.60 ± 0.55, P = 0.036, respectively). In the middle of canine bile duct in contact with drug-eluting stents, there was tendency for less severe inflammation although not statistically significant (1.50 ± 1.00 vs. 1.80 ± 0.84, P = 0.498). Conclusion: Placement of paclitaxel-eluting covered metallic stents in normal canine bile duct was without significant complications despite significant histologic changes from local drug delivery. The results provide a basis for extending the use of a paclitaxel-eluting covered metallic stent in clinical trials. Further studies in patients with malignant biliary obstruction are needed to establish the role of this stent in the palliation of obstructive jaundice.

The Effect of Oral Administration of Alpha Lipoic Acid and Alpha Lipoic Acid Coated Stent in Porcine In-Stent Restenosis Model

Background and Objectives:Alpha lipoic acid (ALA) is beneficial for improving endothelial dysfunction and preventing atherosclerosis-related diseases. We evaluated the affect of ALA on stent restenosis in a porcine model. Materials and Methods:The First experiment: Balloon overdilation injuries were performed in two coronary arteries in 12 pigs. Four weeks after the balloon overdilation injury, 24 bare metal stents were placed for 24 injured coronary arteries. We randomized into two groups (12 stents per group; control group: aspirin and clopidogrel only, ALA group: aspirin and clopidogrel plus 100 mg/kg ALA during 4 weeks). The Second experiment: Stents were randomly implanted in 2 coronary arteries in 8 pigs. Group I was the control stent group (n=8), and group II was the ALA coated stent group (n=8). Follow-up coronary angiogram and histopathologic assessment were performed at 4 weeks after stenting in both experiments. Results:The First experiment On histopathologic analysis, the injury score and internal elastic lamina area did not differ significantly between the two groups. The neointimal area was 7.3±0.9 mm in the control group and 2.2±1.1 mm in the ALA group (p<0.001), and the histopathologic area of stenosis was 75.9±8.5% in the control group and 23.5±10.5% in the ALA group (p<0.001). The Second experiment: The injury score and internal elastic lamina area were not significantly different between the two groups. The neointimal area was 7.4±1.1 mm in the control group and 1.4±0.8 mm in the ALA group (p<0.001), and the histopathologic area of stenosis was 77.6±10.9% in the control group and 15.6±7.6% in the ALA group (p<0.001). Conclusion:Both a high dose of oral ALA and ALA coated stents inhibited neointimal hyperplasia in this porcine coronary artery stent restenosis model. (Korean Circulation J 2006;36:495-502)

The Long-term Clinical Results of a Platelet Glycoprotein IIb/IIIa Receptor Blocker Abciximab: ReoProR Coated Stent in Patients with Coronary Artery Disease

Background :Previously, the inhibition of coronary restenosis with Abciximab (ReoPro®)-coated stent in a porcine model was reported. ReoPro® inhibits platelet aggregation, the proliferation of vascular smooth muscle cells and the inflammatory reaction.Methods :A prospective randomized trial was performed to compare two types of stent for revascularization in the native coronary artery. The primary effective end points were major adverse coronary events (MACE): cardiac death, acute myocardial infarction, target vessel revascularization (TVR) and restenosis at the 6-month clinical and angiographic follow-ups.Results :One hundred and fifty-five patients were enrolled between August 2001 and June 2003. The mean ages (56.0±10.0 vs. 56.9±10.8 years), baseline diameter of stenosis and minimal luminal diameter were no different between the two groups. There was one myocardial infarction and revascularization during the hospital stay in control stent group. During the clinical follow-up there were two myocardial infarctions in control group. Follow-up coronary angiograms were performed in 62.3% (48/77) and 65.4% (51/78) of the coated and control groups, respectively. The diameter of stenosis and late loss were significantly less in the ReoPro®-coated stent group compared with the controls (16.4±5.8% vs. 34.3±6.1%, p=0.009; and 0.33±0.28 mm vs. 0.88±0.41 mm; p=0.002). The restenosis and TVR rates of the ReoPro®-coated stent were relatively lower compared with the control stent [14.6% (7/48) vs. 29.4% (15/51), p=0.062; and 9.2% (7/76) vs. 14.7% (11/75); p=0.327].Conclusion :A ReoPro®-coated stent is safe, and may be effective in the prevention of coronary restenosis.

Biodegradable Self-Expanding Poly-L/D-Lactic Acid Vascular Stent:A Pilot Study in Canine and Porcine Iliac Arteries

To report results of an in vivo pilot study to evaluate the biocompatibility and delivery system of a new biodegradable vascular stent and validate the study design. Two self-expanding intravascular stents, a biodegradable poly-D/L-lactic acid (PLA) and a medical stainless steel stent (Wallstent) were implanted in the common iliac arteries of 2 postpuberal female pigs and 3 laboratory-bred beagle dogs. Specimens were harvested after 45 days in the dogs and 32 days in the pigs for histomorphometry of the stented iliac artery segments. Preliminary measurements were made to assess the reliability of the quantitative histomorphometric measurements before final measurements. Histomorphometry analyses showed that mean luminal diameter and area were decreased in the PLA stent group (1.97+/-0.48 mm and 14+/-6.4 mm2, respectively) compared to the control stent group (4.28+/-0.83 mm and 61+/-19 mm2, respectively). The intimal thickness was higher in the PLA stent group (0.65+/-0.07 mm) than in the control group (0.44+/-0.21 mm). The mean injury score was 0.19+/-0.12 in the PLA stent group and 0.78+/-0.39 in the controls. In the PLA stent group, the mean inflammation score was 1.46+/-0.78 compared to 0.58+/-0.40 in the control group. There were no differences observed between the animal models. The PLA stent showed increased neointimal formation and reduced patency during early follow-up. Mechanical properties of the new biodegradable vascular stents are still inadequate, and the stent and the delivery device require modifications. The study methods were assessed as reliable and reproducible.

Effect of abciximab-coated stent on in-stent intimal hyperplasia in human coronary arteries

The investigators tested whether abciximab-coated stents prevent neointimal hyperplasia (NIH) formation in coronary de novo lesions. Abciximab-coated stents were compared with control stents. All patients underwent follow-up coronary angiography and intravascular ultrasound (IVUS). All stents were successfully deployed, and patients were discharged home without clinical events. At follow-up coronary angiography, the restenosis rate and late loss were 14% and 0.33 +/- 0.28 mm in the abciximab-coated stent group and 28.6% and 0.64 +/- 0.32 mm in the control stent group (p = 0.099 and p = 0.014, respectively). At follow-up IVUS, the intrastent luminal area and intrastent NIH area were 5.7 +/- 1.6 and 2.0 +/- 1.6 mm(2), respectively, in the abciximab-coated stent group and 4.2 +/- 0.8 and 3.4 +/- 1.7 mm(2), respectively, in the control stent group (p = 0.001 and p = 0.001, respectively). Abciximab-coated stents are feasible and significantly inhibit NIH, with potential therapeutic benefit in preventing stent restenosis.