Comparison of vascular remodeling between a bioresorbable poly-L-lactic acid scaffold and a bare metal stent: a 6-month angiography and intravascular ultrasound analysis in porcine iliac arteries

ABSTRACTBioresorbable scaffolds have the potential to overcome several problems associated with metallic stents. Bioresorbable poly-L-lactic acid (PLLA) scaffold implantation for the treatment of peripheral artery disease has already been reported in animal models and clinical trials; however, no studies comparing PLLA scaffolds and bare metal stents (BMSs) with regard to early vascular morphological changes, identified using intravascular ultrasound (IVUS) analysis, have been reported. In this study, PLLA scaffolds and BMSs were implanted bilaterally in iliac arteries of five miniature pigs. Digital subtraction angiography and IVUS were performed before and immediately after stent implantation and at 6-week follow-up. All PLLA scaffolds and BMSs were patent at 6-week follow-up. Per IVUS analysis, the percent area stenosis did not significantly differ between PLLA scaffolds and BMSs (65.7% vs. 67.2%, P = .761). Furthermore, percent vessel lumen change also did not differ significantly. Neointima formation (the neointimal area plus medial area) was significantly less with PLLA scaffolds than with BMSs (15.65 mm2 vs. 25.69 mm2, P < .001). In conclusion, based on IVUS results, short-term results after stent implantation in porcine iliac arteries were comparable between PLLA scaffolds and BMSs. Therefore, PLLA scaffolds are safe and feasible for implantation in peripheral arteries.

Early-Stage Vascular Response between Bare Metal Stent and Drug-Free Bioresorbable Vascular Scaffold in the Small-Sized Peripheral Artery: A Preclinical Study in Porcine Femoral Arteries

Impact of postprocedure minimum stent area on long-term results following abciximab-coated stent implantation: An intravascular ultrasound analysis

Device-related problems of drug-eluting stents, including stent thrombosis related to antiproliferative drugs and polymers, can cause adverse events such as inflammation and neointimal hyperplasia. Stent surface modification, wherein the drug and polymer are not required, may overcome these problems. We developed hydrophilic polyethylene glycol (PEG)-coating and hydrophobic octadecylthiol (ODT)-coating stents without a drug and polymer and evaluated their histopathologic response in a porcine coronary restenosis model. PEG-coating stents (n = 12), bare-metal stents (BMS) (n = 12), and ODT-coating stents (n = 10) were implanted with oversizing in 34 porcine coronary arteries. Four weeks later, the histopathologic response, arterial injury, inflammation, and fibrin scores were analyzed. A p value < 0.05 was considered statistically significant. There were significant differences in the internal elastic lamina area, lumen area, neointimal area, percent area of stenosis, arterial injury score, inflammation score, and fibrin score among the groups. Compared to the BMS or ODT-coating stent group, the PEG-coating stent group had significantly increased internal elastic lamina and lumen area (all p < 0.001) and decreased neointimal area and percent area of stenosis (BMS: p = 0.03 and p < 0.001, respectively; ODT-coating: p = 0.013 and p < 0.001, respectively). Similarly, the PEG-coating group showed significantly lower inflammation and fibrin scores than the BMS or ODT-coating groups (BMS: p = 0.013 and p = 0.007, respectively; ODT-coating: p = 0.014 and p = 0.008, respectively). In conclusion, hydrophilic PEG-coating stent implantation was associated with lower inflammatory response, decreased fibrin deposition, and reduced neointimal hyperplasia than BMS or hydrophobic ODT-coating stent implantation in the porcine coronary restenosis model.

C-Reactive Protein, Clinical Outcome, and Restenosis Rates After Implantation of Different Drug-Eluting Stents

The use of drug eluting stents (DES) in patients with a successfully recanalized chronic total occlusion (CTO) has been associated with a significant decrease in the need for repeat revascularization, and a favorable short-term clinical outcome when compared with the use of bare metal stents (BMS). Our group, however, has previously reported similar rates of target lesion revascularisation (TLR) and major adverse cardiovascular events (MACE) at 3 years follow-up in patients with a successfully opened CTO who were treated with either a sirolimus eluting stent (SES) or a BMS. The objective of this report was to evaluate the outcomes of these patients at 5-years clinical follow-up. A total of 140 (BMS 64, SES 76) patients with successfully opened CTOs were included. Seven patients died in the BMS group whilst nine patients died in the SES group (P = 0.90). Noncardiac death was the major component of all-cause mortality (11 noncardiac deaths vs. 5 cardiac). There were two and three myocardial infarctions (MI) in the BMS and SES group, respectively (P = 1.0). The composite of death and MI occurred in seven (10.9%) and eleven (14.5%) patients in the BMS and SES group, respectively (P = 0.53). Clinically driven TLR was performed in eight patients (12.5%) in the BMS group, and five (6.6%) in the SES group (P = 0.26). Non-TLR target vessel revascularization was performed in one patient in the BMS group, and four in the SES group (P = 0.37). The 5-year device-oriented cumulative MACE rate was 15.6% and 11.8% in the BMS and SES group, respectively (P = 0.56). In patients with a successfully treated CTO, clinical outcome after 5 years was similar between SES and BMS, however, clinically driven TLR was slightly higher in the BMS group.

This study aimed to compare, using optical coherence tomography (OCT), the outcomes of bioabsorbable drug-eluting stent with those of bare metal stent (BMS) following implantation in porcine iliac artery. After the placement of BMS and bioabsorbable drug-eluting stents, we used OCT and digital subtraction angiography to investigate stent appositions, arterial neointima, evagination, and restenosis at 1 and 3 months. At 1 and 3 months after stent implantation, OCT study was performed to investigate 32 stents and 21 788 struts. Thirty-three malapposed struts were found in the bioabsorbable drug-eluting stent groups and 2 were found in BMS groups. The average neointimal thickness, area, and in-stent stenosis were significantly lower in bioabsorbable drug-eluting stents than in BMS, while the frequency of malapposed struts was higher in the bioresorbable drug-eluting stent groups. Average neointimal thickness was lower in bioabsorbable drug-eluting stents than in BMS at 1 (0.19 ± 0.09 vs 0.67 ± 0.75 mm; P < .001) and 3 months (0.21 ± 0.08 vs 1.52 ± 0.28 mm; P < .001). Our study suggested that bioabsorbable drug-eluting stent is more effective in decreasing arterial restenosis than BMS in animal models.

Background-This article reports the 2-year clinical, angiographic, and intravascular ultrasound outcomes of the everolimus-eluting stent (EES) compared with the paclitaxel-eluting stent (PES) in the randomized SPIRIT II trial. Methods and Results-This was a prospective, single-blind clinical trial in which a total of 300 patients with de novo native coronary artery lesions were randomized to either EES or PES in a 3:1 fashion. Clinical follow-up was planned at 2 years in all patients. A subset of 152 patients underwent serial angiographic and intravascular ultrasound analyses at 6 months and 2 years. After 2 years, target lesion failure (cardiac death, myocardial infarction, and ischemia-driven target lesion revascularization) rates were 6.6% and 11% in EES and PES, respectively (P0.31). At 6 months, a significant reduction in angiographic in-stent late loss and percentage volume obstruction measured by intravascular ultrasound was observed in the EES group. However, at 2-year follow-up, a late increased intimal hyperplasia growth after implantation of an EES was observed. There were no significant differences between EES and PES for in-stent late loss (EES, 0.330.37 mm versus PES, 0.340.34 mm; P0.84) and percentage volume obstruction (EES, 5.186.22% versus PES, 5.806.31%; P0.65) at 2 years. The incidence of stent thrombosis was low and comparable in both groups (EES, 0.9%; PES, 1.4%). Conclusions-Although the previously reported angiographic and clinical superiority of the EES has vanished over time, this report confirms and extends the previously demonstrated noninferiority in terms of in-stent late loss of the EES when compared with the PES up to 2-year follow-up. There were no significant differences between EES and PES in clinical, angiographic and intravascular ultrasound outcomes at 2 years. (Circ Cardiovasc Intervent. 2009;2:339-347.)

Mid-term Efficacy and Safety of Drug-coated Balloon versus Nitinol Bare Metal Stent for Primary Lesions in Femoropopliteal Artery Disease

Background: Octogenarians have been under-represented in percutaneous coronary intervention (PCI) trials, thus making difficult to choose the best type of stent in this patient population. We compared the outcomes of drug eluting (DES) and bare metal stent (BMS) at one year after implantation in this special population. Methods: A total of 320 patients over 80 years undergoing PCI with BMS (n=218) or DES (n=102) between January 2000 and March 2008 were retrospectively studied. In-hospital and one year major adverse cardiac events (MACE) defined as cardiac related death, non-fatal myocardial infarction, target vessel (TVR) and target lesion revascularization (TLR) were compared between the two groups. Cox regression analysis was used for data analysis. Results: The cumulative incidence of in-hospital MACE between the BMS and DES group were similar (3.6% vs 2.9%; P=0.32). The one year incidence of MACE event was higher in the BMS group (18.8% vs 9.8%, adjusted relative risk [RR] 2.33; 95% confidence interval [C.I.]: 1.12 to 4.86; P=0.02) Figure-1. Diabetes mellitus was an independent predictor for increased MACE event (adjusted RR: 1.99; C.I: 1.06 to 3.77, P= 0.03). One year cumulative incidence of TLR and TVR was higher in the BMS group (10.0% vs 3.9% adjusted RR : 2.94 ; C.I. 1.01 to 8.59 P=0.05) Figure 2. Conclusion: During one year follow up, octogenarians treated with BMS had an increased risk of MACE compared with those treated with DES. DES should be preferred in indications recognized from current PCI guidelines.

Objective — The aim of this study is to compare anti-inflammatory and intimal hyperplasia inhibiting efficacy between the Firebird rapamycin drug-eluting stent and a bare metal stent in a porcine coronary injury model.Methods — Twelve rapamycin drug-eluting stents (Firebird), and 12 bare metal stents (BMS) were deployed with the oversizing method into porcine coronary arteries. Coronary angiography, histopathological and immunocytochemistry analysis were carried out at week 4 after stenting.Results — The distribution of stented vessels, diameter of reference vessels, and post-procedural minimal lumen diameter were compared between the two groups. At week 4 of follow-up, quantitative coronary angiography (QCA) showed that the minimal lumen diameter and late lumen loss were greater, and percent stenosis was less in the Firebird stent group than in the bare metal stent group. In the histopathological analysis, compared to the BMS group, injury score in the Firebird stent group (1.87 ± 0.16 vs. 1.32 ± 0.13) and inflammation score (1.86 ± 0.55 vs.1.12 ± 0.35) decreased, P < 0.05.There are significant differences for neointimal area (4.60 ± 1.39 mm2 in the BMS group vs. 1.51 ± 0.45 mm2 in the TCS group, P < 0.05). The lumen area in the Firebird stent group enlarged (3.24 ± 0.93 mm2 in the BMS group vs. 4.34 ± 0.93 mm2 in the Firebird stent group, P < 0.05). Immunohistochemistry revealed that the Firebird stent suppressed cell proliferation (Ki67) and expression of nuclear factor-kappaB (NF-κB) in the arterial wall.Conclusion — The Firebird stent showed suppression of constrictive remodelling, inhibition of neointimal hyperplasia through antiproliferation, and anti-inflammation acts via attenuated NF-kκ activation, which has proved to be a feasible method for preventing restenosis after coronary angioplasty in pigs.

Safety and efficacy of drug-eluting stents in women: a patient-level pooled analysis of randomised trials

The aim of this study was to compare dextran and Poly(l-lactide) (PLLA) polymer stent coatings as mediators for sirolimus (SRL) drug elution in a porcine coronary model. The bare metal stent (BMS) surface was first coated with a layer of SRL and then either dextran (DSS, a natural polymer) or PLA (PSS, a synthetic polymer). The release velocity of SRL was slightly faster in DSS than PSS over the first 7 days (78.5% and 62.3%, respectively, n = 10, p < 0.05) and continued to 28 days in both groups. The contact angle was dramatically decreased in DSS (38.7° ± 1.24) compared to BMS and PSS groups (72.7° ± 5.32 and 81.1º ± 1.70, respectively, n = 10, p < 0.05). Smooth muscle cell migration was arrested in both the DSS and PSS-treated groups compared to that in the nontreated group (4.2% ± 0.31, 5.8% ± 0.60, 80.0% ± 4.4, respectively, n = 10, p < 0.05). In the animal study, there were no significant differences in the injury score, the internal elastic lamina, and the lumen area among the groups. However, percent area stenosis was significantly decreased in the SRL-containing group (27.5% ± 2.52 in DSS and 27.9% ± 3.30 in PSS) compared to BMS (35.9% ± 3.51, p < 0.05). The fibrin score was higher in the PSS (2.9 ± 0.31) than BMS (2.1 ± 0.12) and DSS (2.5 ± 0.66). The inflammation score in the DSS (0.7 ± 0.21) was similar to that in the BMS (0.7 ± 0.12), which was dramatically lower than that PSS (1.5 ± 0.18, p < 0.005). Immunofluorescence analysis revealed that endothelialization was increased and inflammation prevented in the DSS. These results suggest that dextran may be useful for the fabrication of drug eluting stent as an alternative existing synthetic polymer. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 301-310, 2017.

To evaluate the clinical value of primary stenting for treating peripheral arterial diseases in below-the-knee arteries by comparing to percutaneous transluminal angioplasty (PTA). PubMed, ScienceDirect, Embase, and CBM databases were searched for relevant articles. Based on the different types of stents, we divided the primary stent group into the bare metal stent(BMS) group and drug-eluting stent(DES) group. The outcome measures were immediate technical success, freedom from target vessel revascularization (TVR-free) rate and limb salvage. Finally, 14 studies (published between 2001 and 2012) satisfying the inclusion criteria were identified. A total of 3 278 patients and 3 699 limbs constituted our final study population. The technical success rate of PTA was 90.95% (95% confidence interval (CI) 86.25%-94.15%). Only one study reported a technical failure of 4% (5/118) in the primary stent group. There were no significant differences in the 1-year primary patency and TVR-free rates between the PTA group and BMS groups (P > 0.05 and P > 0.05), respectively. The pooled estimates of 1-year primary patency and TVR-free rate in DES group were 85.05% (95%CI 79.95%-89.02%) and 90.52% (95%CI 83.68%-94.67%), respectively, which were better than those of the BMS (P < 0.001) and PTA groups (P < 0.001). The pooled estimate of 1-year limb salvage in the PTA, BMS, and DES groups was 88.41% (95%CI 84.53%-91.43%), 94.41% (95%CI 89.52%-97.1%), and 96.81% (95%CI 94.04%-98.32%), respectively. The BMS and DES groups had higher limb salvage rates than the PTA group (P < 0.001 for both comparisons). The rates of severe complications were low both in the PTA and primary stent groups. Although the influence analysis showed rather robust results, the heterogeneity was quite high and they were not adjusted for confounding variables. Primary BMS implantation had no advantage over PTA in reducing restenosis or revascularization for infrapopliteal disease. Primary DES implantation seems to be a promising treatment for focal infrapopliteal lesions.

Efficacy of a Polyphosphazene Nanocoat in Reducing Thrombogenicity, In-stent Stenosis, and Inflammatory Response in Porcine Renal and Iliac Artery Stents