Favorable vessel healing after nobori biolimus A9-eluting stent implantation-6- and 12-month follow-up by optical coherence tomography.

BACKGROUND: Nobori is a novel biolimus A9-eluting stent (BES) coated with a biodegradable polymer only on the abluminal side, which degrades over 6-9 months post-stent deployment. The course of vessel reaction after deployment at these time points remains unclear. METHODS AND RESULTS: We serially evaluated 28 BES implanted in de novo coronary lesions of 23 patients using optical coherence tomography (OCT) at 6 and 12 months post-stenting. Standard OCT variables, the percentage of stent with peri-strut low-intensity area (PLIA, a region around stent struts homogenously showing lesser intensity than the surrounding tissue, suggesting fibrin deposition or impaired neointima maturation) and that with in-stent thrombi were evaluated. There was a significant, but small increase in neointimal thickness (72 ± 23 to 82 ± 25 µm, P=0.006) from the 6- to the 12-month follow-up, without a significant decrease in minimum lumen area (P=0.30). The incidences of uncovered and malapposed struts were low at 6 months and reduced further at 12 months (3.96 ± 3.97% to 1.51 ± 1.63%, P=0.001, and 0.50 ± 1.84% to 0.06 ± 0.24%, P=0.20, respectively). The frequency of stent with PLIA decreased during the follow-up (57% to 32%, P=0.05) and that with in-stent thrombi also numerically decreased (7% to 0%, P=0.24). CONCLUSIONS: Neointimal hyperplasia was persistently suppressed following BES implantation up to 12 months. Simultaneously, favorable vessel healing was achieved at 6 months without a delaying adverse reaction for up to 12 months.

One-year safety and effectiveness of the Agent paclitaxel-coated balloon for the treatment of small vessel disease and in-stent restenosis.

The Agent device consists of a semi-compliant balloon catheter, which is coated with a therapeutic low-dose formulation of paclitaxel (2 µg/mm2) blended with an inactive excipient acetyl-tri-n-butyl citrate (ATBC). AGENT Japan SV is a randomized controlled study that enrolled 150 patients from 14 Japanese sites treated with Agent or SeQuent Please paclitaxel-coated balloon. This study also includes a single-arm substudy evaluating the safety and effectiveness of Agent in patients with in-stent restenosis (ISR). Patients with a single de novo native lesion (lesion length ≤ 28 mm and reference diameter ≥ 2.00 to < 3.00 mm) were randomized 2:1 to receive either Agent (n = 101) or SeQuent Please (n = 49). The ISR substudy enrolled 30 patients with lesion length ≤ 28 mm and reference diameter ≥ 2.00 to ≤ 4.00 mm. In the SV RCT, target lesion failure (TLF) at 1 year occurred in four patients treated with Agent (4.0%) versus one patient with SeQuent Please (2.0%; P = 1.00). None of the patients in either treatment arm died. There were no significant differences in the rates of myocardial infarction, target lesion revascularization and target lesion thrombosis through 1 year. In the ISR substudy, the 1-year rates of TLF and target lesion thrombosis were 6.7% and 0.0%, respectively. These data support the safety and effectiveness of the Agent paclitaxel-coated balloon in patients with small vessels and ISR.

Comparison of MECHANISM of early and late vascular responses following treatment of ST-elevation acute myocardial infarction with two different everolimus-eluting stents: a randomized controlled trial of biodegradable versus durable polymer stents.

The early and mid-term arterial healing profile of biodegradable polymer-coated everolimus-eluting stents (BP-EES) is unclear, especially in ST-segment elevation myocardial infarction (STEMI) culprit lesions. This study aimed to compare early- and mid-term arterial healing between durable polymer-coated everolimus-eluting stents (DP-EES) and BP-EES in STEMI patients. In a prospective, multicenter, non-inferiority trial, STEMI patients were randomized to receive BP-EES (n = 60) or DP-EES (n = 60). The primary endpoint of this study was the mean percentage of covered struts (%covered struts) on FD-OCT 2 weeks post-PCI. Key secondary endpoints included the percentage of uncovered struts, frequency of abnormal intra-stent tissue, and percentage of malapposed struts by FD-OCT 2 weeks and 12 months post-PCI. They underwent serial frequency-domain optical coherence tomography (FD-OCT) evaluations immediately after percutaneous coronary intervention, and at 2 weeks and at 12 months after the procedure. The primary endpoint of %covered struts at 2 weeks was 71.4% in BP-EES and 72.3% in DP-EES [risk difference - 0.94%, lower limit of one-sided 95% confidence interval (CI) - 5.6; Pnon-inferiority = 0.0756]. At 12 months, the mean percentage of uncovered struts was significantly lower [1.73% (95% CI 0.28-3.17) vs. 4.81% (95% CI 3.52-6.09); p = 0.002], and the average malapposed volume was significantly smaller in the BP-EES group than in the DP-EES group (p = 0.002). At 12 months, BP-EES had a significantly larger average neointimal area with a significantly smaller average intra-stent tissue unevenness score than DP-EES, suggesting more uniform neointimal coverage with BP-EES. Strut coverage was comparable between BP-EES and DP-EES at 2 weeks. Non-inferiority could not be proven because of an insufficient sample size. The significantly better arterial healing with BP-EES at 12 months suggests a safer profile for STEMI culprit lesions.Trial registration: jRCTs022180024 https://jrct.niph.go.jp/en-latest-detail/jRCTs022180024.

A serial optical frequency-domain imaging study of early and late vascular responses to bioresorbable-polymer sirolimus-eluting stents for the treatment of acute myocardial infarction and stable coronary artery disease patients: results of the MECHANISM-ULTIMASTER study.

The purpose of this study was to assess early and late vascular healing in response to bioresorbable-polymer sirolimus-eluting stents (BP-SESs) for the treatment of patients with ST-elevation myocardial infarction (STEMI) and stable coronary artery disease (CAD). A total of 106 patients with STEMI and 101 patients with stable-CAD were enrolled. Optical frequency-domain images were acquired at baseline, at 1- or 3-month follow-up, and at 12-month follow-up. In the STEMI and CAD cohorts, the percentage of uncovered struts (%US) was significantly and remarkably decreased during early two points and at 12-month (the STEMI cohort: 1-month: 18.75 ± 0.78%, 3-month: 10.19 ± 0.77%, 12-month: 1.80 ± 0.72%; p < 0.001, the CAD cohort: 1-month: 9.44 ± 0.78%, 3-month: 7.78 ± 0.78%, 12-month: 1.07 ± 0.73%; p < 0.001 respectively). The average peri-strut low-intensity area (PLIA) score in the STEMI cohort was significantly decreased during follow-up period (1.90 ± 1.14, 1.18 ± 1.25, and 1.01 ± 0.72; p ≤ 0.001), whereas the one in the CAD cohort was not significantly changed (0.89 ± 1.24, 0.67 ± 1.07, and 0.64 ± 0.72; p = 0.59). In comparison with both groups, differences of %US and PLIA score at early two points were almost disappeared or close at 12 months. The strut-coverage and healing processes in the early phase after BP-SES implantation were significantly improved in both cohorts, especially markedly in STEMI patients. At 1 year, qualitatively and quantitatively consistent neointimal coverage was achieved in both pathogenetic groups.

Comparison of serial optical coherence tomography imaging following aggressive stent expansion technique: insight from the MECHANISM study.

To compare early vascular healing following cobalt-chromium everolimus-eluting stent (CoCr-EES) implantation between groups with or without aggressive stent expansion in patients treated by CoCr-EES for stable coronary artery disease (CAD). Seventy-one stable CAD lesions underwent CoCr-EES implantation and analysis of serial optical coherence tomography (OCT) images obtained post-procedure and at early-term (1- or 3-month) follow-up. The endpoints of this study were neointimal thickness at the time of 1- or 3-month OCT and presence and healing of stent edge dissection. Aggressive stent expansion was defined as a lesion complying with ILUMIEN III sizing protocol; that is, external elastic lamina (EEL) diameter minus maximum balloon diameter ≤ 0.25 mm.  Comparing groups with and without aggressive stent expansion, median neointimal thickness at 1 and 3 months after CoCr-EES implantation was similar (1 month: 0.031 mm vs. 0.041 mm, respectively, p = 0.27; 3 months: 0.036 mm vs. 0.040 mm, respectively, p = 0.84). Regarding stent edge findings, the presence of any stent edge dissection immediately after percutaneous coronary intervention was also similar between the groups (25% vs. 15%, respectively; p = 0.30) and most stent edge dissections resolved completely within 3 months, regardless of location or dissection severity. After 1 year, no clinically driven target lesion revascularization or stent thrombosis was observed in either cohort. Even after aggressive stent expansion, early neointimal proliferation appeared modest with CoCr-EES implantation, and most stent edge dissections had resolved by 3 months. These findings may support the feasibility of EEL-based sizing by pre-stenting OCT.

STELLIUM 1: First-in-man follow-up evaluation of bioabsorbable polymer-coated paclitaxel-eluting stent.

BACKGROUND: Durable polymers used for first-generation drug-eluting stents (DES) potentially contribute to persistent inflammation and late DES thrombosis. The vascular response to the Stellium stent, which is coated with an absorbable polymer for slow release of low-dose paclitaxel, was evaluated in the present study. METHODS AND RESULTS: The 37 patients with stable angina were implanted with 47 Stellium stents. Quantitative coronary angiography (QCA) was performed at baseline, and QCA and optical coherence tomography (OCT) were performed at 6 months post-implant. The primary endpoint was major adverse cardiac events (MACE). At 6 months, 1 case of MACE occurred because of total occlusion of a protected left main artery. In-stent and segment binary restenosis rates were both 0%. In-stent late loss was 0.19 ± 0.54 mm. Altogether, 5,564 struts were visualized by OCT and mean neointimal thickness was 150.03 ± 146.36 µm. The number of well-apposed struts with and without neointima overlay was 5,135 (92.29%) and 396 (7.12%), respectively. Peri-strut low intensity was observed in 518 struts (9.31%). CONCLUSIONS: This first-in-man study of the Stellium stent shows the promising possibility of bioabsorbable polymeric surface coating paclitaxel-eluting stents out to 6 months. The low rate of peri-strut low intensity suggests low cellular toxicity of the Stellium stent compared with the first-generation DES.

Cut-off value of strut-vessel distance for the resolution of acute incomplete stent apposition in the early phase using serial optical coherence tomography after cobalt-chromium everolimus-eluting stent implantation.

OBJECTIVE: The purpose of this study was to identify a cut-off value to predict the resolution of incomplete-stent-apposition (ISA) after cobalt-chromium everolimus-eluting stent (CoCr-EES) implantation at early follow-up. BACKGROUND: To date, appropriate stent apposition at the acute period using intracoronary imaging has been recommended because persistent ISA is considered to be a risk factor for stent thrombosis. We examined the indices for resolving acute ISA. In particular, we determined the cut-off value for strut vessel distance (SV-distance) as visualized by optical coherence tomography (OCT) at 8 months after CoCr-EES implantation. However, the cut-off value of SV-distance for the earlier resolution of ISA is unclear. METHODS: A total of 95 cases and 103 stents were registered in the MECHANISM Elective substudy. The SV-distance was measured at the deepest site of the target malapposition and every 1 mm from the proximal edge to the distal edge of the mal-apposed area using OCT. Cut-off values for ISA resolution at 1 and 3 months were estimated by SV-distance using receiver operating characteristic analysis. RESULTS: The total number of analyzed struts was 14,418 at the 1-month follow-up and 11,986 at the 3-month follow-up. The optimal SV-distance cut-off values just after stent implantation to predict ISA resolution were 185 µm at the 1-month follow-up and 195 µm at the 3-month follow-up. CONCLUSION: For resolution of ISA, SV-distance cut-off values of 185 µm at 1 month postimplantation and 195 µm at 3 months postimplantation can be used as the index of endpoint of the percutaneous coronary intervention.

Cut-off value of mal-apposition volume and depth for resolution at early phase of acute incomplete stent apposition after CoCr-EES implantation.

The purpose of this study was to clarify a cut-off value for acute incomplete stent apposition (ISA) volume and maximum-depth to predict ISA resolution at 1- and 3-month follow-up in patients treated with cobalt-chromium everolimus-eluting stents. In total, 95 cases and 103 stents were registered in the MECHANISM-Elective sub-study. Acute ISA-volume was measured by the trapezoid rule. ISA resolution of cut-off value at 1- and 3-month was estimated by ISA-volume and maximum-depth using receiver operatorating characteristic curve analysis. The total number of analysed acute ISAs was 202 in the 1-month group and 225 in the 3-month group. A total of 123 ISAs at 1-month and a total of 169 ISAs at 3-month had been resolved. The cut-off value of ISA resolution by ISA-volume was 0.169 mm3 at 1-month (AUC: 0.725, sensitivity: 72.2%, specificity: 61.0%) and 0.295 mm3 at 3-month (AUC: 0.757, sensitivity: 75.0%, specificity: 60.4%). The cut-off value of ISA resolution by ISA maximum-depth demonstrated was 0.285 mm at 1-month (area under curve (AUC): 0.789, sensitivity: 70.9%, specificity: 69.9%) and 0.305 mm at 3-month (AUC: 0.663, sensitivity: 60.7%, specificity: 66.9%). Incidence of ISA resolution was significantly lower in combination with cut-off values of ISA-volume and maximum-depth (33%, p < 0.001, at 1-month; 56%, p = 0.003, at 3-month). Combining the cut-off value of ISA-volume with the maximum-depth might be helpful to consider the endpoint of the PCI procedure.

Vascular response to paclitaxel-eluting nitinol self-expanding stent in superficial femoral artery lesions: post-implantation angioscopic findings from the SHIMEJI trial (Suppression of vascular wall Healing after IMplantation of drug Eluting peripheral stent in Japanese patients with the Infra inguinal lesion: serial angioscopic observation).

The aim of this study was to elucidate the vascular responses to paclitaxel-eluting stent (Zilver PTX stent) in superficial femoral artery lesion at different elapsed times using angioscopy. Patients who received Zilver PTX stent implantation from five centers were enrolled. We performed angioscopic examinations at 2, 6, and 12 months after implantation and evaluated neointimal coverage (NIC) grade, intra-stent thrombus (IS-Th) grade, and presence of yellow plaque. NIC grade 0 was defined as stent struts exposed; grade 1, struts transparently visible although covered; grade 2, struts embedded in the neointima, but translucent; and grade 3, struts fully embedded and invisible. IS-Th was graded as follows: grade 0 (none), 1 (focal), and 2 (diffusely spread). Angioscopic follow-up evaluation was performed at 2 months (25 patients, 42 lesions), 6 months (18 patients, 23 stents), and 12 months (14 patients, 24 stents) after stent implantation. Dominant NIC grade significantly increased over time; however, 16.3% of the cases had NIC grade 1 or 2 at 12 months. IS-Th grade decreased; however IS-Th and yellow plaque were persistently observed in 62.5% and 83.3% cases, respectively, at 12 months. An ongoing healing response was observed at 12 months after implantation; however, thrombogenic findings were noted. Prolonged dual antiplatelet therapy could potentially enhance the clinical utility of Zilver PTX.

Coronary risk factors associated with OCT macrophage images and their response after CoCr everolimus-eluting stent implantation in patients with stable coronary artery disease.

BACKGROUND AND AIMS: The aim of this study was to evaluate the accumulation of optical coherence tomography (OCT)-macrophages and OCT findings after CoCr everolimus-eluting stent placement, in addition to coronary risk factors. METHODS: A total of 89 lesions in 89 patients were registered in the 1- and 3-month cohort of the multi-centre study. Lesion characteristics and post-procedure OCT images were evaluated immediately and 1 and 3 months after stenting. Patients were divided into low and high macrophage grade groups based on the median macrophage grade. RESULTS: Low-density lipoprotein cholesterol (LDL-C) levels, the prevalence of diabetes mellitus, HbA1c and blood glucose levels in the high macrophage grade group were significantly higher than in the low macrophage grade group (p = 0.025, p = 0.040, p = 0.032, and p = 0.010). Moreover, total lipid arc and length and number of thin-cap fibroatheromas (TCFAs) in the high macrophage grade group were significantly higher than in the low macrophage group (p = 0.008, p = 0.002, and p = 0.012). After CoCr everolimus-eluting stenting, there was a trend towards a greater number, height, and area of irregular protrusions in the high macrophage grade group compared to the low macrophage grade group (p = 0.091, p = 0.059, and p = 0.085). Multivariate logistic regression analysis showed that diabetes mellitus was a significant predictor of high macrophage grades (odds ratio: 2.8, 95% CI: 1.1-7.3, p = 0.030). CONCLUSIONS: The accumulation of OCT-macrophages was associated with diabetes mellitus in patients with coronary artery disease. Moreover, macrophage accumulation and diabetes mellitus may be associated with irregular protrusions just after stenting.

Two-year vascular responses to drug-eluting stents with biodegradable polymer versus durable polymer: An optical coherence tomography sub-study of the NEXT.

BACKGROUND: This study aimed to compare very late vascular response after stent implantation between everolimus-eluting stent (EES) with a thin, non-adhesive, durable, biocompatible fluorinated polymer and biolimus-eluting stent (BES) with a biodegradable polymer by optical coherence tomography (OCT). METHODS AND RESULTS: In the NOBORI-BES Versus XIENCE V/PROMUS-EES Trial (NEXT), a formal OCT substudy investigated 48 patients (27 EES-treated lesions in 23 patients and 28 BES-treated lesions in 25 patients) with 2-year (18-30 months) follow-up imaging at 18 centers. The percentage of uncovered strut by neointima was significantly lower in EES compared with BES (2.1±4.7% vs. 7.9±10.8%, p=0.013). The percentage of malapposed strut was not different between EES and BES (0.1±0.3% vs. 0.5±1.3%, p=0.138). The frequency of stent with evagination, which is identified as outward bulges in the luminal contour between struts, was significantly lower in EES compared with BES (22% vs. 86%, p<0.001). The frequency of neoatherosclerosis was not different between EES and BES (11% vs. 11%, p=1.000). CONCLUSIONS: At 2 years after stent implantation, uncovered stent strut by neointima and evagination were less frequently observed in EES compared with BES. This OCT study suggests that the very late vascular response is different between EES and BES.

Dual Antiplatelet Therapy for 6 Versus 18 Months After Biodegradable Polymer Drug-Eluting Stent Implantation.

OBJECTIVES: The NIPPON (Nobori Dual Antiplatelet Therapy as Appropriate Duration) study was a multicenter randomized investigation of the noninferiority of short-term versus long-term dual antiplatelet therapy (DAPT) in patients with implantation of the Nobori drug-eluting stent (DES) (Terumo, Tokyo, Japan), which has a biodegradable abluminal coating. BACKGROUND: The optimum duration of DAPT for patients with a biodegradable polymer-coated DES is unclear. METHODS: The subjects were 3,773 patients with stable or acute coronary syndromes undergoing Nobori stent implantation. They were randomized 1:1 to receive DAPT for 6 or 18 months. The primary endpoint was net adverse clinical and cerebrovascular events (NACCE) (all-cause mortality, myocardial infarction, stroke, and major bleeding) from 6 to 18 months after stenting. Intention-to-treat analysis was performed in 3,307 patients who were followed for at least 6 months. RESULTS: NACCE occurred in 34 patients (2.1%) receiving short-term DAPT and 24 patients (1.5%) receiving long-term DAPT (difference 0.6%, 95% confidence interval [CI]: 1.5 to 0.3). Because the lower limit of the 95% CI was inside the specified margin of -2%, noninferiority of short-term DAPT was confirmed. Mortality was 1.0% with short-term DAPT versus 0.4% with long-term DAPT, whereas myocardial infarction was 0.2% versus 0.1%, and major bleeding was 0.7% versus 0.7%, respectively. The estimated probability of NACCE was lower in the long-term DAPT group (hazard ratio: 1.44, 95% CI: 0.86 to 2.43). CONCLUSIONS: Six months of DAPT was not inferior to 18 months of DAPT following implantation of a DES with a biodegradable abluminal coating. However, this result needs to be interpreted with caution given the open-label design and wide noninferiority margin of the present study. (Nobori Dual Antiplatelet Therapy as Appropriate Duration [NIPPON]; NCT01514227).

Optical coherence tomography study of chronic-phase vessel healing after implantation of bare metal and paclitaxel-eluting self-expanding nitinol stents in the superficial femoral artery.

BACKGROUND: This study aimed to assess chronic-phase suppression of neointimal proliferation and arterial healing following paclitaxel-coated (PTX) and bare metal stent (BMS) implantation in the superficial femoral artery using optical coherence tomography (OCT). METHODS: Twenty-five patients with 68 stents underwent an 8-month OCT follow-up. Besides standard OCT variables, neointimal characterization and frequencies of peri-strut low-intensity area (PLIA), macrophage accumulation, and in-stent thrombi were evaluated. RESULTS: The mean neointimal thickness was significantly less with PTX stents (544.9±202.2 µm vs. 865.0±230.6 µm, p<0.0001). The covered and uncovered strut frequencies were significantly smaller and larger, respectively, in the PTX stent group vs. the BMS group (93.7% vs. 99.4%; p<0.0001, 4.0% vs. 0.4%; p<0.0001, respectively). Heterogeneous neointima was only observed in the PTX stent group (12.5% vs. 0%, p=0.017). The frequencies of PLIA and macrophage accumulation were significantly greater in the PTX stent group (87.2% vs. 67.6%, p=0.001 and 46% vs. 9.1%, p=0.003, respectively). CONCLUSION: After 8 months, reduced neointimal proliferation was observed with PTX stent implantation. On the other hand, delayed arterial healing was observed compared with BMS.

Serial Optical Coherence Tomography Evaluation at 6, 12, and 24 Months After Biolimus A9-Eluting Biodegradable Polymer-Coated Stent Implantation.

BACKGROUND: The Nobori (Terumo Corporation, Tokyo, Japan) is a biolimus A9-eluting stent (BES) featured with a biodegradable polymer coated on the abluminal side only. We previously reported that favourable vessel healing was achieved at 6-12 months after BES implantation. However, detailed long-term vessel reaction after BES deployment is unclear. METHODS: Twenty-two BESs were serially evaluated using optical coherence tomography (OCT) at 6, 12, and 24 months after stenting. Average neointimal thickness, uncovered struts, and neointimal unevenness score (each cross-section as maximum neointimal thickness in 1 cross section divided by the average neointimal thickness of the same cross-section) were manually measured. In addition, we evaluated the percentage of struts with peri-strut low-intensity area (a region around stent struts that homogenously showed less intensity than the surrounding tissue, which suggests fibrin deposition or impaired neointima maturation), thrombi, and atherogenic neointimas (neointimas containing a diffuse border and poor-signal region with invisible struts due to marked signal attenuation). RESULTS: Serial OCT observation revealed a small gradual increase in neointimal thickness from 6 to 24 months (73 ± 24 µm; 81 ± 26 µm; and 108 ± 35 µm, respectively, P = 0.001) with a nonsignificant decrease in the lumen area (6.36 ± 1.98 mm(2); 6.18 ± 2.04 mm(2); and 5.87 ± 2.06 mm(2); P = 0.72). Frequency of uncovered struts (3.89 ± 3.91%; 1.55 ± 1.63%; and 0.23 ± 0.67%; P = 0.001), neointimal unevenness score (1.95 ± 0.18% to 1.86 ± 0.19% to 1.78 ± 0.17; P = 0.012), percentage of thrombi (5%, 0%, and 0%; P = 0.37) and peri-strut low-intensity area (6.8%, 5.1%, and 1.6%; P = 0.017) decreased from 6 to 12 and 24 months. Atherogenic neointima was not observed in the event-free OCT cohort. CONCLUSIONS: The Nobori stent achieved acceptable long-term vessel healing, mostly without adverse vessel reactions.

Comparison of vascular response between durable and biodegradable polymer-based drug-eluting stents in a porcine coronary artery model.

AIMS: Biodegradable polymer-based drug-eluting stents are thought to be safer than durable polymer-based stents. However, the long-term vascular response remains unclear. The aim of this study was to compare the biocompatibility of durable polymer-based sirolimus-eluting (SES) and everolimus-eluting (EES) stents with biodegradable polymer-based biolimus-eluting (BES) stents in a porcine coronary model. Stents were implanted in porcine coronaries. Acetylcholine challenge tests and optical coherence tomography (OCT) examination were performed at one month. Animals were sacrificed at three and six months (n=6 each), and the stents were analysed histologically. At one month, acetylcholine challenge tests revealed a trend towards greatest vasoconstriction in SES, less in BES, and least in EES, but the differences were not significant. OCT analysis demonstrated the highest incidence of uncovered struts in SES, followed by BES, while EES showed almost complete strut coverage (41.7±27.0%, 24.5±23.8%, 0.4±0.8%, respectively; p=0.004). Upon histological analysis at three months, SES showed a significantly higher inflammatory score than BES and EES (2.9±1.4, 0.8±0.9, 0.5±0.4, respectively; p=0.001), and this was maintained at six months (1.6±1.5, 0.3±0.3, 0.4±0.6, respectively; p=0.049). While SES showed an increased inflammatory reaction, EES and BES showed minimal inflammation. These results indicate that the late inflammatory reaction does not necessarily depend on degradability of the polymer, if the combination of the drug, metal, and polymer is biocompatible.

Polymer-free cerivastatin-eluting stent shows superior neointimal inhibition with preserved vasomotor function compared to polymer-based paclitaxel-eluting stent in rabbit iliac arteries.

AIMS: The present study was designed to evaluate vasomotor function and vascular biological responses following a novel non-polymeric cerivastatin-eluting stent (CES) versus polymer-based paclitaxel-eluting stent (PES) in a rabbit iliac artery model. Optimisation of DES components and non-polymeric stents may contribute to vascular healing and beneficial to vasomotor function. METHODS AND RESULTS: In vitro human aortic and coronary smooth muscle cells (hASMC & hCSMC), as well as endothelial cells (hAEC & hCEC) were cultured. IC50 curves were determined for cerivastatin (CER). In vivo PES (n=6) and CES (n=12) stents were implanted in nine rabbits. Vasomotor function was investigated at 28 days by acetylcholine (ACh) followed by histopathological and histomorphometric analyses. CER was cytotoxic to hASMC and hCSMC (IC50s of 10-6 M and 10-5 M, respectively), although such cytotoxic effects were not observed for hAEC and hCEC at maximal study dose. PES-associated vasodilation response to endothelial-dependent ACh was significantly suppressed at both proximal and distal adjacent arterial segments, as compared to CES. Furthermore, microscopically, neointimal inhibition quantified by the neointimal cross-sectional area (IA) was superior with CES (0.60 + or - 0.27 mm(2)) compared to PES (1.35 + or - 0.16 mm(2); P <0.05). Medial area was smaller for PES (0.3 + or - 0.04 mm(2)) than CES (0.5 + or - 0.03 mm(2), p <0.001). Additionally, significant inflammation and fibrin deposition was clearly evidenced in PES compared to CES (p <0.05). CONCLUSIONS: CER elicits a differential effect on hSMC compared to hEC in vitro. In contrast to PES, a novel bioabsorbable sol-gel coated CES demonstrated effective neointimal inhibition with less vessel wall toxicity accompanied by preservation of vasomotor function in the rabbit iliac model.

Low-dose paclitaxel elution by novel bioerodible sol-gel coating on stents inhibits neointima with low toxicity in porcine coronary arteries.

OBJECTIVES: The present study was designed to evaluate a novel bioerodible sol-gel film coated paclitaxel-eluting stent (sol-gel-PES, 3 microg per stent) in a porcine coronary artery model. BACKGROUND: Although current polymer-based PES decrease restenosis, the permanent polymer and bound drug have raised concerns regarding delayed vessel healing and late stent thrombosis. METHODS: Polymer-based PES (poly-PES, n = 8), sol-gel-PES (n = 15), bare metal (BMS, n = 14), and sol-gel film only (sham, n = 12), stents were implanted in 17 juvenile pigs. Animals were terminated 28 days post-implant for angiographic restudy and complete histopathologic and histomorphometric analyses. RESULTS: Angiographic late loss was equally reduced for both poly-PES and sol-gel-PES (0.51 +/- 0.64 and 0.61 +/- 0.52 mm, respectively) compared to both BMS and sham (0.98 +/- 0.74 and 1.25 +/- 0.72 mm, p < 0.05). Similarly beneficial results were observed for histomorphometric parameters of neointimal thickness and area, yielding reductions of in-stent stenosis by 43% and 48% for poly-PES, as well as 31% and 37% for sol-gel-PES, vs. BMS and sham, respectively (p < 0.05). Re-endothelialization was complete in all groups. Although the inflammatory cell infiltration and intramural thrombus scores were no different between poly- and sol-gel-PES, medial necrosis was increased for poly-PES (p < 0.05 vs. all others). CONCLUSIONS: A novel bioerodible sol-gel film coated with low-dose paclitaxel demonstrates less toxicity to the coronary tunica media, while retaining effective inhibition of neointimal formation at 28 days.