Effect of educational intervention on the appropriate use of oral antimicrobials in oral and maxillofacial surgery: a retrospective secondary data analysis.

BACKGROUND: In Japan, oral third-generation cephalosporins with broad-spectrum activity are commonly prescribed in the practices of dentistry and oral surgery. However, there are few reports on the appropriate use of antibiotics in the field of oral surgery. This study aimed to evaluate the appropriateness of antibiotic use before and after an educational intervention in the Department of Oral and Maxillofacial Surgery, Kobe University Hospital. METHODS: The use of oral antibiotics was investigated among inpatients and outpatients before and after an educational intervention conducted by the antimicrobial stewardship team. Additionally, the frequency of surgical site infection after the surgical removal of an impacted third mandibular molar under general anesthesia and the prevalence of adverse effects of the prescribed antibiotics were comparatively evaluated between 2013 and 2018. RESULTS: After the educational intervention, a remarkable reduction was noted in the prescription of oral third-generation cephalosporins, but increased use of penicillins was noted among outpatients. There was reduced use of macrolides and quinolones in outpatients. Although a similar trend was seen for inpatients, the use of quinolones increased in this population. Despite the change in the pattern of antibiotic prescription, inpatients who underwent mandibular third molar extraction between 2013 and 2018 did not show a significant increase in the prevalence of surgical site infections (6.2% vs. 1.8%, p = .336) and adverse effects of drugs (2.1% vs. 0%, p = .466). CONCLUSIONS: This study suggests that the judicious use of oral antibiotics is possible through conscious and habitual practice of appropriate antibiotic use. However, further investigation is required to develop measures for appropriate use of oral antibiotics.

Three-Year Clinical Outcomes of Everolimus-Eluting Stents From the Post-Marketing Surveillance Study of Cobalt-Chromium Everolimus-Eluting Stent (XIENCE V/PROMUS) in Japan.

BACKGROUND: The Cobalt-Chromium Everolimus-Eluting Stent (CoCr-EES) Post-marketing Surveillance (PMS) is a prospective multicenter registry designed to evaluate the safety and efficacy of XIENCE V/PROMUS everolimus-eluting stents in routine clinical practice at 47 centers representative of the clinical environment in Japan. METHODS AND RESULTS: We enrolled 2,010 consecutive patients (2,649 lesions) who underwent PCI using CoCr-EES. Clinical outcomes were evaluated for up to 3 years. Clinical follow-up was available in 1,930 patients (96%) at 3 years. Major adverse cardiovascular events (MACE) occurred in 6.8% of patients, including cardiac death (1.7%), myocardial infarction (1.5%), and clinically driven target lesion revascularization (CD-TLR, 4.2%). Late CD-TLR rate was 0.8% from 1 to 2 years, and 0.5% from 2 to 3 years. Definite or probable stent thrombosis occurred in 7 patients (0.3%) up to 1 year. There was no very late definite or probable stent thrombosis from 1 to 3 years. Significant independent predictors for MACE were hemodialysis, prior coronary intervention, triple-vessel coronary artery disease, and age >70 years. CONCLUSIONS: Three-year clinical outcomes from the CoCr-EES PMS demonstrated a low incidence of clinical events. There was no major concern about very late stent thrombosis or late catch-up phenomenon in patients treated with EES in routine clinical practice in Japan.

Impact of Implantation Technique and Plaque Morphology on Strut Embedment and Scaffold Expansion of Polylactide Bioresorbable Scaffold　- Insights From ABSORB Japan Trial.

BACKGROUND: The optimal implantation technique for the bioresorbable scaffold (Absorb, Abbott Vascular) is still a matter of debate. The purpose of the present study was to evaluate the effect of implantation technique on strut embedment and scaffold expansion.Methods and Results:Strut embedment depth and scaffold expansion index assessed by optical coherence tomography (OCT) (minimum scaffold area/reference vessel area) were evaluated in the ABSORB Japan trial (OCT subgroup: 87 lesions) with respect to implantation technique using either quantitative coronary angiography (QCA) or OCT. Strut embedment was assessed at the strut level (n=667), while scaffold expansion was assessed at the lesion level (n=81). The mean embedment depth was 63±59 µm. Balloon sizing and inflation pressure had no direct effect on strut embedment. Plaque morphology affected strut embedment [nonatherosclerotic (58.9±54.3 µm), fibroatheroma (73.3±59.6 µm), fibrous plaque (59.7±51.1 µm), and fibrocalcific plaque (-3.1±61.6 µm, negative value means malapposition), P <0.001]. The balloon-artery ratio positively correlated with the expansion index. This relationship was stronger when the OCT-derived reference vessel diameter (RVD) was used as a reference for balloon selection rather than the QCA-derived one [predilatation (Pearson correlation r: QCA: 0.167 vs. OCT: 0.552), postdilatation (QCA: 0.316 vs. OCT: 0.717)]. CONCLUSIONS: Underlying plaque morphology influenced strut embedment, whereas implantation technique had no direct effect on it. Optimal balloon sizing based on OCT-derived RVD might be recommended. However, the safety of such a strategy should be investigated in a prospective trial. (Circ J 2016; 80: 2317-2326).

An Aspirin-Free Strategy for Immediate Treatment Following Complex Percutaneous Coronary Intervention.

BACKGROUND: There was no study evaluating the effects of an aspirin-free strategy in patients undergoing complex percutaneous coronary intervention (PCI). OBJECTIVES: The authors aimed to evaluate the efficacy and safety of an aspirin-free strategy in patients undergoing complex PCI. METHODS: We conducted the prespecified subgroup analysis based on complex PCI in the STOPDAPT-3 (ShorT and OPtimal duration of Dual AntiPlatelet Therapy after everolimus-eluting cobalt-chromium stent-3), which randomly compared low-dose prasugrel (3.75 mg/d) monotherapy to dual antiplatelet therapy (DAPT) with low-dose prasugrel and aspirin in patients with acute coronary syndrome or high bleeding risk. Complex PCI was defined as any of the following 6 criteria: 3 vessels treated, ≥3 stents implanted, ≥3 lesions treated, bifurcation with 2 stents implanted, total stent length >60 mm, or a target of chronic total occlusion. The coprimary endpoints were major bleeding events (Bleeding Academic Research Consortium 3 or 5) and cardiovascular events (a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischemic stroke) at 1 month. RESULTS: Of the 5,966 study patients, there were 1,230 patients (20.6%) with complex PCI. Regardless of complex PCI, the effects of no aspirin relative to DAPT were not significant for the coprimary bleeding (complex PCI: 5.30% vs 3.70%; HR: 1.44; 95% CI: 0.84-2.47; P = 0.18 and noncomplex PCI: 4.26% vs 4.97%; HR: 0.85; 95% CI: 0.65-1.11; P = 0.24; P for interaction = 0.08) and cardiovascular (complex PCI: 5.78% vs 5.93%; HR: 0.98; 95% CI: 0.62-1.55; P = 0.92 and noncomplex PCI: 3.70% vs 3.10%; HR: 1.20; 95% CI: 0.88-1.63; P = 0.25; P for interaction = 0.48) endpoints without significant interactions. CONCLUSIONS: The effects of the aspirin-free strategy relative to standard DAPT for the cardiovascular and major bleeding events were not different regardless of complex PCI. (ShorT and OPtimal duration of Dual AntiPlatelet Therapy after everolimus-eluting cobalt-chromium stent-3 [STOPDAPT-3]; NCT04609111).

Biodegradable or durable polymer drug-eluting stents in patients with coronary artery disease: ten-year outcomes of the randomised NEXT Trial.

BACKGROUND: There are no randomised trials reporting clinical outcomes of biodegradable polymer biolimus-eluting stents (BP-BES) and durable polymer everolimus-eluting stents (DP-EES) at 10 years. AIMS: We aimed to compare the 10-year clinical outcomes between BP-BES and DP-EES. METHODS: The randomised NOBORI Biolimus-Eluting Versus XIENCE/PROMUS Everolimus-eluting Stent Trial (NEXT) was originally designed to evaluate the non-inferiority of BP-BES relative to DP-EES with the primary efficacy endpoint of target lesion revascularisation (TLR) at 1 year and the primary safety endpoint of death or myocardial infarction (MI) at 3 years. In this extended follow-up study, clinical outcomes were compared from 1 year after stent implantation up to 10 years between patients with BP-BES and DP-EES. RESULTS: From May to October 2011, NEXT enrolled a total of 3,241 patients from 98 centres in Japan. The current study population consisted of 2,417 patients (1,204 patients with BP-BES and 1,213 with DP-EES) from 66 centres that agreed to participate in the extended study. Complete 10-year follow-up was achieved in 87.5% of patients. The cumulative 10-year incidence of death or MI was 34.0% in the BP-BES group and 33.1% in the DP-EES group (hazard ratio [HR] 1.04, 95% confidence interval [CI]: 0.90-1.20; p=0.58). TLR occurred in 15.9% of patients in the BP-BES group and in 14.1% of the DP-EES group (HR 1.12, 95% CI: 0.90-1.40; p=0.32). In a landmark analysis at 1 year, the cumulative incidences of death or MI and TLR were not significantly different between the 2 groups. CONCLUSIONS: The safety and efficacy outcomes for BP-BES were not significantly different from those for DP-EES at 1 year and up to 10 years after stent implantation.

Randomized comparison of the Nobori biolimus A9-eluting stent with the sirolimus-eluting stent in patients with stenosis in native coronary arteries.

OBJECTIVES: The aim of this randomized-controlled trial is to compare biolimus A9-eluting stent (Nobori) to sirolimus eluting stent (Cypher). BACKGROUND: The Nobori coronary stent is coated only abluminally with a biodegradable polymer, poly-lactic acid, and the antiproliferative agent biolimus A9. This stent has been studied in randomized trials versus Taxus Express and Taxus Liberte and showed noninferiority and superiority for in-stent late loss. This is the first randomized trial of Nobori stent versus Cypher stent. METHODS: We conducted a randomized (3:2), controlled trial comparing Nobori and Cypher, in 335 patients (198 Nobori and 137 Cypher) at 15 centers in Japan. Patients with de-novo lesions in up to two native coronary arteries were considered for enrollment. The primary endpoint was freedom from target vessel failure (TVF), a composite of cardiac death, myocardial infarction, and target vessel revascularization at 9 months. RESULTS: At 9 months, the primary endpoint of freedom from TVF was 92.6% in Nobori and 93.8% in Cypher arm (noninferiority test P < 0.001). As main secondary endpoints, the in-stent late loss was 0.12 ± 0.30 mm and 0.14 ± 0.34 mm in Nobori and Cypher stents, respectively. Target lesion revascularization was 0.5% in Nobori and 3.9% in Cypher treated patients (P = 0.04). Definite and probable stent thromboses were not recorded in any patient. CONCLUSIONS: Despite the relatively small number of patients, this well controlled clinical trial confirmed the primary hypothesis of non-inferiority of the Nobori biolimus A9-eluting stent to the Cypher sirolimus-eluting stent for freedom from TVF. Both stents showed excellent midterm results.

Interstitial deletion of 18q: comparative genomic hybridization array analysis of 46, XX,del(18)(q21.2.q21.33).

BACKGROUND: Interstitial deletion of chromosome 18q is rare, making it difficult to assign phenotypes to particular cytogenetic deletions. CASE: We present an 18-year-old female with an interstitial deletion of chromosome 18q21.2-q21.33. The clinical features included severe psychomotor retardation with mild growth retardation, hypotonia, midfacial hypoplasia, carp-shaped mouth, hypertelorism, strabismus, narrow upward slant palpebral fissures, short philtrum, everted lower lip, malformed ears, flat nasal bridge, and epicanthic folds. Brain abnormalities, such as agenesis of the corpus callosum, and abnormalities of the hands and feet were absent. Initially, the deletion was recognized as 18q21.1-q21.31 by conventional chromosomal analysis, and microarray-based comparative genomic hybridization revealed a 9.6-Mb deletion at 18q21.2-q21.33. The deletion included the transcription factor 4 gene and the methyl-CpG binding domain protein 2 (MBD2) gene, but not the MBD1 gene. CONCLUSIONS: The deletion of the transcription factor 4 gene suggested a possible contribution of the deletion to the patient's facial abnormalities, as observed in Pitt-Hopkins syndrome. Together with other reported cases with interstitial deletion of 18q, a possible contribution of haploinsufficiency in both MBD1 and MBD2 genes to a Rett syndrome-like phenotype was suggested, but further genetic studies on other cases are necessary to clarify the genotype-phenotype correlation.

Biodegradable polymer drug-eluting stent vs. contemporary durable polymer drug-eluting stents in patients with diabetes: a meta-analysis of randomized controlled trials.

AIMS: The biodegradable polymer drug-eluting stents (BP-DES) offer controlled drug elution and complete degradation of the polymer over time, eventually lowering the risk for chronic inflammation and neoatherosclerosis, which can be particularly helpful in patients with diabetes. While BP-DES and durable polymer drug-eluting stents (DP-DES) have demonstrated comparable efficacy in all-comers population, their efficacy and safety in patients with diabetes remains uncertain. METHODS AND RESULTS: Electronic databases were systematically searched for randomized controlled trials (RCTs) comparing BP-DES with contemporary DP-DES in patients with diabetes. Study investigators were contacted to obtain additional data. The primary outcome was efficacy in terms of target-vessel revascularization (TVR) and target-lesion revascularization (TLR). We also evaluated the following safety outcomes separately: all-cause mortality, cardiac mortality, myocardial infarction (MI), and definite or probable stent thrombosis. Eleven RCTs including 5190 diabetic patients were included. At the longest available follow-up (mean 2.7 years), there was no significant difference in TLR [relative risk (RR): 1.02, 95% confidence interval (CI): 0.85-1.24; P = 0.80] or TVR (RR: 1.04, 95% CI: 0.81-1.34; P = 0.76). Safety outcomes of all-cause mortality, cardiac mortality, and MI were similar between the two groups. Stent thrombosis rates were also similar between BP-DES and DP-DES groups (1.66% vs. 1.83%; RR: 0.84, 95% CI: 0.54-1.31; P = 0.45). The heterogeneity was low and fixed-effect model yielded similar results. Meta-regression analysis showed no relationship between insulin requiring diabetes and difference in TLR or stent thrombosis between BP-DES and DP-DES. CONCLUSION: Overall, BP-DESs have similar safety and efficacy profiles compared to contemporary DP-DES in patients with diabetes.

Randomized Comparison Between Everolimus-Eluting Bioresorbable Scaffold and Metallic Stent: Multimodality Imaging Through 3 Years.

OBJECTIVES: The aim of this study was to investigate the vascular responses and fates of the scaffold after bioresorbable vascular scaffold (BVS) implantation using multimodality imaging. BACKGROUND: Serial comprehensive image assessments after BVS implantation in the context of a randomized trial have not yet been reported. METHODS: In the ABSORB Japan trial, 400 patients were randomized to a BVS (n = 266) or a cobalt-chromium everolimus-eluting stent (n = 134). Through 3 years, patients underwent serial angiography and intravascular ultrasound or optical coherence tomography (OCT). RESULTS: Luminal dimension at 3 years was consistently smaller with the BVS than with the cobalt-chromium everolimus-eluting stent (mean angiographic minimal luminal diameter 2.04 ± 0.63 mm vs. 2.40 ± 0.56 mm, mean difference -0.37 mm [95% confidence interval: -0.50 to -0.24 mm]; p < 0.001), mainly because of smaller device area (6.13 ± 2.03 mm2 vs. 7.15 ± 2.16 mm2, mean difference -1.04 mm2 [95% confidence interval: -1.66 to -0.42 mm2]; p < 0.001), and larger neointimal area (2.10 ± 0.61 mm2 vs. 1.86 ± 0.64 mm2, mean difference 0.24 mm2 [95% confidence interval: 0.06 to 0.43 mm2]; p = 0.01) by OCT. BVS-treated vessels did not show previously reported favorable vessel responses, such as positive vessel remodeling, late luminal enlargement, and restoration of vasomotion, although the OCT-based healing score was on average zero (interquartile range: 0.00 to 0.00). At 3 years, intraluminal scaffold dismantling (ISD) was observed in 14% of BVS. On serial OCT, ISD was observed in 6 lesions at 2 years, where the struts had been fully apposed at post-procedure, while ISD was observed in 12 lesions at 3 years, where 8 lesions were free from ISD on 2-year OCT. In 5 cases of very late scaffold thrombosis, strut discontinuities were detected in all 4 cases with available OCT immediately before reintervention. CONCLUSIONS: In this multimodality serial imaging study, luminal dimension at 3 years was smaller with the BVS than with the cobalt-chromium everolimus-eluting stent. ISD, suspected to be one of the mechanisms of very late BVS thrombosis, was observed in a substantial proportion of cases at 3 years, which developed between post-procedure and 2 years and even beyond 2 years. (AVJ-301 Clinical Trial: A Clinical Evaluation of AVJ-301 [Absorb™ BVS] in Japanese Population [ABSORB JAPAN]; NCT01844284).

Two-year results after coronary stenting of small vessels in Japanese population using 2.25-mm diameter sirolimus-eluting stent with bioresorbable polymer: primary and long-term outcomes of CENTURY JSV study.

Percutaneous coronary intervention (PCI) in coronary artery disease (CAD) with very small vessels remains challenging. The aim of this study is to evaluate the safety and effectiveness of the 2.25-mm diameter Ultimaster sirolimus-eluting stent in the treatment of Japanese patients with CAD due to lesions in very small vessels. The CENTURY JSV study is a prospective, multicentre, single-arm study. Seventy patients with lesions deemed suitable for implantation of a 2.25-mm diameter stent were enrolled at seven hospitals in Japan. Patients underwent clinical follow-up at 1-, 9-month, 1-, and 2-year after the PCI procedure. The primary endpoint was the major adverse cardiac event (MACE), a composite of cardiac death, target vessel myocardial infarction (MI), and clinically driven target lesion revascularization (TLR) free rate at 9-month following the procedure. The MACE-free rate was 97.1%, and the lower limit of the two-sided 95% confidence interval (CI) was 90.1%, which exceeded the threshold of 80% set as the performance goal. Angiographic in-stent and in-segment late loss at 9-month were 0.22 ± 0.31 and - 0.02 ± 0.34 mm, respectively. Between 9 months and 2 years, two additional TLRs occurred. Stent thrombosis, bleeding and vascular complication did not occur throughout 2 years. The 2.25-mm diameter Ultimaster® bioresorbable-polymer sirolimus-eluting stent is safe and effective for treating lesions in very small coronary arteries throughout 2 years after stent implantation.Clinical trial registration: UMIN000012928.

Clinical Outcomes Following Implantation of Thin-Strut, Bioabsorbable Polymer-Coated, Everolimus-Eluting SYNERGY Stents.

BACKGROUND: The thin-strut SYNERGY stent has an abluminal everolimus-eluting bioabsorbable polymer coating designed to facilitate vascular healing and reduce risk of stent thrombosis. In the multicenter, randomized EVOLVE II trial (The EVOLVE II Clinical Trial to Assess the SYNERGY Stent System for the Treatment of Atherosclerotic Lesion[s]), SYNERGY was noninferior to the durable polymer PROMUS Element Plus everolimus-eluting stent for the primary end point of 1-year target lesion failure. Longer-term clinical follow-up will support the relative efficacy and safety of SYNERGY. METHODS: Patients with ≤3 native coronary lesions (reference vessel diameter ≥2.25-≤4.00 mm; length ≤34 mm) in ≤2 major epicardial vessels were randomized 1:1 to SYNERGY (N=838) or PROMUS Element Plus (N=846). EVOLVE II included a Diabetes substudy which pooled patients with diabetes mellitus from the randomized controlled trial (n=263) and from a sequential, single-arm substudy (N=203). RESULTS: The 5-year target lesion failure rate was 14.3% for SYNERGY and 14.2% for PROMUS Element Plus (P=0.91). Landmark analysis demonstrated similar rates of target lesion failure from discharge to 1-year (P=0.90) and from 1 to 5 years (P=0.94). Definite/probable stent thrombosis was infrequent in both arms (SYNERGY 0.7% versus PROMUS Element Plus 0.9%; P=0.75). There were no significant differences in the rates of cardiac death, myocardial infarction, or revascularization. Among patients with diabetes mellitus, the target lesion failure rate to 1-year was noninferior to a prespecified performance goal and to 5 years was 17.0%. CONCLUSIONS: SYNERGY demonstrated comparable outcomes to PROMUS Element Plus, with low rates of stent thrombosis and adverse events through 5 years of follow-up. Five-year clinical outcomes were favorable in patients with diabetes mellitus. These data support the long-term safety and effectiveness of SYNERGY in a broad range of patients. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01665053.

Preclinical evaluation of a paclitaxel-incorporated nanoparticle-coated balloon in rabbit and porcine models.

BACKGROUND: The main drawback of current available drug coated balloons (DCB) is that a certain percentage of the coated drug is lost in the bloodstream during its delivery to the target lesion. We integrated the nanoparticle-mediated drug delivery technology and polydimethylsiloxane (PDMS) as a new excipient to facilitate an efficient drug delivery and uptake by endothelial cells. The present study aimed to evaluate the efficacy of the new DCB. METHOD AND RESULTS: The novel DCB were coated with 5.6mg of paclitaxel-incorporated nanoparticles using PDMS. The efficacy of the new DCB was examined in rabbit iliac stent model (n=12) and in the swine in-stent restenosis model (n=8) by quantitative coronary angiography (QCA) and optical coherence tomography (OCT). At 28days follow-up in the swine in-stent restenosis model, the area stenosis was significantly lower in DCB group as compared with that of the control group in OCT analysis (0.31±0.05 vs 0.49±0.06, p=0.04) though there was no significant differences observed in the rabbit iliac stent model in QCA and OCT analysis. CONCLUSION: The study results indicated that the paclitaxel-incorporated nanoparticle-coated balloon using PDMS has an inhibitory effect for the proliferation of smooth muscle cell in a swine coronary in-stent restenosis model.

Midterm clinical outcomes with everolimus-eluting bioresorbable scaffolds versus everolimus-eluting metallic stents for percutaneous coronary interventions: a meta-analysis of randomised trials.

bioresorbable vascular scaffold (BVS) versus an everolimus-eluting metallic stent (EES) for percutaneous coronary interventions. METHODS AND RESULTS: We performed a meta-analysis of aggregate data by searching Medline, EMBASE, Cochrane databases and proceedings of international meetings for randomised trials reporting the clinical outcomes beyond one year of patients treated with BVS versus EES. The primary efficacy and safety outcomes were target lesion failure (TLF) and definite/probable stent (scaffold) thrombosis (ST), respectively. Secondary outcomes were the individual components of the primary efficacy outcome (cardiac death, target vessel myocardial infarction [MI], and ischaemia-driven target lesion revascularisation [ID-TLR]). A total of 5,583 patients randomly received BVS (n=3,261) or EES (n=2,322) in seven trials. Weighted median follow-up was 26.6 months. Patients treated with BVS versus EES showed a higher risk of TLF (odds ratio [OR] 1.35, 95% confidence interval [CI]: 1.11-1.65; p=0.0028) due to a higher risk of target vessel MI (OR 1.68, 95% CI: 1.21-2.33; p=0.008) and ID-TLR (OR 1.42, 95% CI: 1.10-1.84; p=0.007) though the risk for cardiac death was not statistically different (OR 0.89, 95% CI: 0.55-1.43; p=0.56). Patients treated with BVS versus EES showed a higher risk of definite/probable ST (OR 3.24, 95% CI: 1.92-5.49; p<0.0001), particularly in the period beyond one year after implantation (OR 4.03, 95% CI: 1.49-10.87; p=0.006). CONCLUSIONS: At midterm follow-up, patients treated with BVS as compared to those treated with EES display a higher risk of target lesion failure and scaffold thrombosis.

Efficacy and Safety of the Absorb Bioresorbable Vascular Scaffold in Females and Males: Results of an Individual Patient-Level Pooled Meta-Analysis of Randomized Controlled Trials.

OBJECTIVES: Because females are under-represented in coronary trials, this study sought to assess the relative safety and efficacy of Absorb bioresorbable vascular scaffold (BVS) (Abbott Vascular, Santa Clara, California) and the Xience everolimus-eluting stent in females compared with males. BACKGROUND: The Absorb everolimus-eluting BVS provides drug delivery and mechanical support similar to a metallic drug-eluting stent, followed by resorption and restoration of more normal vascular structure with the potential to improve late clinical outcomes. METHODS: The ABSORB II, ABSORB III, ABSORB Japan, and ABSORB China trials were pooled. Baseline clinical, angiography, procedural variables, and 2-year outcomes were analyzed by sex and device. RESULTS: Among 3,384 randomized patients, 932 (27.5%) were female. Females were older, more often had diabetes and hypertension, but had less everolimus-eluting stent, 3-vessel disease, and smoking compared with males (all p≤0.001). The 2-year rates of target lesion failure with BVS versus everolimus-eluting stent in females were 8.9% versus 6.2% (study-level adjusted hazard ratio: 1.47; 95% confidence interval [CI]: 0.88 to 2.46) and 8.9% versus 6.4% in males (HR: 1.40; 95% CI: 1.02 to 1.92; pinteraction = 0.85). There were no significant interactions between sex and device type for any of the components of target lesion failure. CONCLUSIONS: The relative treatment effects of BVS and everolimus-eluting stent for the 2-year rates of target lesion failure and other cardiovascular outcomes were consistent in females and males.

Prevention of neointimal formation using miRNA-126-containing nanoparticle-conjugated stents in a rabbit model.

BACKGROUND: Despite recent progress with drug-eluting stents, restenosis and thrombosis after endovascular intervention are still major limitations in the treatment of cardiovascular diseases. These problems are possibly caused by inappropriate inhibition of neointimal formation and retardation of re-endothelialization on the surface of the stents. miR-126 has been shown to have the potential to enhance vascular endothelial cell proliferation. METHODS AND RESULTS: We designed and constructed a 27-nt double strand RNA (dsRNA) conjugated to cholesterol, which has high membrane permeability, and formed mature miR-126 after transfection. For site-specific induction of miR-126, we utilized poly (DL-lactide-co-glycolide) nanoparticles (NPs). miR-126-dsRNA-containing NPs (miR-126 NPs) significantly reduced the protein expression of a previously identified miR-126 target, SPRED1, in human umbilical vascular endothelial cells (HUVECs), and miR-126 NPs enhanced the proliferation and migration of HUVECs. On the other hand, miR-126 NPs reduced the proliferation and migration of vascular smooth muscle cells, via the suppression of IRS-1. Finally, we developed a stent system that eluted miR-126. This delivery system exhibited significant inhibition of neointimal formation in a rabbit model of restenosis. CONCLUSIONS: miR-126 NP-conjugated stents significantly inhibited the development of neointimal hyperplasia in rabbits. The present study may indicate the possibility of a novel therapeutic option to prevent restenosis after angioplasty.

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.

Efficacy and Safety of the Absorb Everolimus-Eluting Bioresorbable Scaffold for Treatment of Patients With Diabetes Mellitus: Results of the Absorb Diabetic Substudy.

OBJECTIVES: The study sought to evaluate the efficacy and safety of the Absorb everolimus-eluting bioresorbable vascular scaffold (BVS) (Abbott Vascular, Abbott Park, Illinois) in patients with diabetes mellitus. BACKGROUND: Randomized, controlled trials have demonstrated comparable clinical outcomes following percutaneous coronary intervention with either Absorb BVS or metallic Xience everolimus-eluting stent. However, these trials lack power required to provide reliable treatment effect estimates in this high-risk population. METHODS: In a pre-specified, powered analysis, patients with diabetes who received ≥1 Absorb were pooled from the ABSORB II, III, and JAPAN randomized trials and from the single arm ABSORB EXTEND registry. The study composite primary endpoint was target lesion failure (TLF) at 1 year following Absorb BVS compared with a performance goal of 12.7%. RESULTS: Among 754 diabetic patients included in analysis (27.3% insulin treated), the 1-year TLF rate was 8.3% (upper 1-sided 95% confidence limit: 10.1%; p = 0.0001 vs. performance goal). Scaffold thrombosis (definite or probable) was observed in 2.3% of patients. Multivariable regression identified older age, insulin treatment, and smaller pre-procedure reference vessel diameter as significant independent predictors of 1-year TLF. CONCLUSIONS: The Absorb diabetic substudy suggests efficacy and safety of the Absorb BVS for treatment of patients with diabetes mellitus.

Prospective multi-center registry to evaluate efficacy and safety of the newly developed diamond-like carbon-coated cobalt-chromium coronary stent system.

The purpose of this multi-center, non-randomized, and open-label clinical trial was to determine the non-inferiority of diamond-like carbon (DLC)-coated cobalt-chromium coronary stent, the MOMO DLC coronary stent, relative to commercially available bare-metal stents (MULTI-LINK VISION®). Nineteen centers in Japan participated. The study cohort consisted of 99 patients from 19 Japanese centers with single or double native coronary vessel disease with de novo and restenosis lesions who met the study eligibility criteria. This cohort formed the safety analysis set. The efficacy analysis set consisted of 98 patients (one case was excluded for violating the eligibility criteria). The primary endpoint was target vessel failure (TVF) rate at 9 months after stent placement. Of the 98 efficacy analysis set patients, TVF occurred in 11 patients (11.2 %, 95 % confidence interval 5.7-19.2 %) at 9 months after the index stent implantation. The upper 95 % confidence interval for TVF of the study stent was lower than that previously reported for the commercially available MULTI-LINK VISION® (19.6 %), demonstrating non-inferiority of the study stent to MULTI-LINK VISION®. All the TVF cases were related to target vascular revascularization. None of the cases developed in-stent thrombosis or myocardial infarction. The average in-stent late loss and binary restenosis rate at the 6-month follow-up angiography were 0.69 mm and 10.5 %, respectively, which are lower than the reported values for commercially available bare-metal stents. In conclusion, the current pivotal clinical study evaluating the new MOMO DLC-coated coronary stent suggested its low rates of TVF and angiographic binary restenosis, and small in-stent late loss, although the data were considered preliminary considering the small sample size and single arm study design.