Application Of Drug-eluting Stents Research Articles

Integrating Network Pharmacology and Experimental Verification to Explore the Targets and Mechanism for Panax Notoginseng Saponins against Coronary In-stent Restenosis.

Despite widespread application of drug-eluting stents in coronary intervention, in-stent restenosis (ISR) is still a daunting complication in clinical practice. Panax notoginseng saponins (PNS) are considered to be effective herb compounds for preventing ISR. This study aimed to elucidate the targets and mechanisms of PNS in ISR prevention using network pharmacology approaches and experimental verification. Relevant targets of PNS active compounds were collected from the HERB database and PharmMapper. The ISR-related targets were obtained from the GeneCards database and the Comparative Toxicogenomics Database. The GO and KEGG enrichment analysis was performed using R software. The String database and Cytoscape software were employed to build the PPI and compounds-targets-pathways-disease networks. Finally, Molecular docking performed by Autodock Vina and cellular experiments were used to validate network pharmacology results. There were 40 common targets between PNS targets and ISR targets. GO analysis revealed that these targets focused on multiple ISR-related biological processes, including cell proliferation and migration, cell adhesion, inflammatory response, and anti-thrombosis and so on. The KEGG enrichment results suggested that PNS could regulate multiple signaling pathways to inhibit or delay the development and occurrence of ISR. The molecular docking and cellular experiments results verified the network pharmacology results. This study demonstrated that the potential molecular mechanisms of PNS for ISR prevention involved multiple compounds, targets, and pathways. These findings provide a theoretical reference and experimental basis for the clinical application and product development of PNS for the prevention of ISR.

Fabrication and application of drug eluting stent for peripheral artery disease

Fabrication and application of drug eluting stent for peripheral artery disease

Association between Oxidative Burden and Restenosis: A Case-Control Study.

Background In-stent restenosis (ISR) is an important clinical complication that occurs following stent implantation. The application of drug-eluting stents (DES) and even consumption of drugs such as antiplatelet agents and statins are not completely effective in reducing ISR risk. Since the number of these patients continues to rise, it is pivotal to detect patients who are at a higher risk of ISR. In addition, identification of biochemical markers of ISR could give the right perspective on choosing the proper strategy to treat these patients. Several pathophysiological pathways including oxidative stress (OS) are implicated in the progression of ISR. Hence, this study aimed to evaluate the association between oxidative/anti-oxidative markers and ISR. Methods This was a case-control study which comprised 21 ISR, 26 NISR (non-ISR), and 20 healthy subjects. The serum levels of OS markers including malondialdehyde (MDA), thiol groups (GSH), total antioxidant capacity (TAC), and the activity of serum antioxidant enzymes such as glutathione peroxidase (GPx) and superoxide dismutase (SOD) were assessed by colorimetric methods. The overall oxidative burden was assessed using a pro-oxidant-antioxidant balance (PAB) assay. Results MDA levels were considerably higher in the ISR group when compared to healthy subjects (P = 0.004). PAB also indicated significantly higher values in both ISR (P < 0.001) and NISR (P < 0.001) groups related to healthy subjects. No significant differences were observed between the studied groups regarding thiol levels, antioxidant enzyme activities, and TAC. Multinomial logistic regression analysis showed that elevated serum levels of MDA (OR: 1.028, 95% CI: 1.008-1.048; P = 0.006) and PAB (OR: 1.076, 95% CI: 1.017-1.139; P = 0.011) were significantly associated with higher ISR risk; however, increased values of TAC (OR: 0.990, 95% CI: 0.982-0.999; P = 0.030) were significantly associated with decreased ISR risk, while after adjustment for confounders, only SOD activity (OR: 0.0, 95% CI: 0.0-0.0; P < 0.001) and PAB value (OR: 1.866, 95% CI: 1.856-1.900; P < 0.001) showed association with ISR risk. Conclusion According to the present findings, some oxidative and antioxidative markers like PAB and SOD activity showed the potential in the prediction of ISR risk.

The Use of Bioactive Polymers for Intervention and Tissue Engineering: The New Frontier for Cardiovascular Therapy

Coronary heart disease remains one of the leading causes of death in most countries. Healthcare improvements have seen a shift in the presentation of disease with a reducing number of ST-segment elevation myocardial infarctions (STEMIs), largely due to earlier reperfusion strategies such as percutaneous coronary intervention (PCI). Stents have revolutionized the care of these patients, but the long-term effects of these devices have been brought to the fore. The conceptual and technologic evolution of these devices from bare-metal stents led to the creation and wide application of drug-eluting stents; further research introduced the idea of polymer-based resorbable stents. We look at the evolution of stents and the multiple advantages and disadvantages offered by each of the different polymers used to make stents in order to identify what the stent of the future may consist of whilst highlighting properties that are beneficial to the patient alongside the role of the surgeon, the cardiologist, engineers, chemists, and biophysicists in creating the ideal stent.

Synthesis and Appraisal of Natural Drug-Polymer-Based Matrices Relevant to the Application of Drug-Eluting Coronary Stent Coatings.

Cardiovascular diseases are becoming a leading cause of death in the world, and attention is being paid to develop natural drug-based treatment to cure heart diseases. Curcumin, ginger, and magnolol are pharmaceutically active in many ways, having properties including anticoagulation, antiproliferation, anti-inflammatory, and antioxidant, and may be used to synthesis coatings for drug-eluting stents to treat cardiovascular diseases. In the present investigation, a degradable polymer with varying molecular weights was used as a drug carrier to control the degradation of polymer; three different natural drugs such as curcumin, magnolol, and ginger were used owing to their reported pharmacological properties. The results of in vitro measurements of all three natural drugs released from drug-loaded polymeric films showed an initial burst release followed by a sustained release for up to 38 days of measurement. On the other hand, different levels of hemocompatibility were observed by varying concentrations of natural drugs in human erythrocytes. As per the ASTM F756 standard, ginger having low concentration showed optimum hemocompatibility with regard to the drug-eluting stent application as compared with magnolol and curcumin concentrations, which showed suboptimal hemocompatibility and fall in the range of mild-to-severe blood toxicity category. The structure of the coating films was characterized by Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM) with results suggesting that there was no chemical bonding between the polymer and drug. Thus, according to this study, it can be concluded that after more detailed in vitro testing such as hemocompatibility tests and platelet adhesion testing, ginger can be a better candidate as a drug-coating material for drug-eluting stent applications.

An asymmetric surface coating strategy for improved corrosion resistance and vascular compatibility of magnesium alloy stents

Magnesium (Mg) and its alloys are promising materials for biodegradable drug-eluting stent applications, but their rapid corrosion remains a major challenge for clinical practice. Considerable efforts have been made to develop an efficient surface coating that can provide higher Mg stent corrosion resistance, sustained drug-delivery capability, and vascular compatibility. Herein, we introduce poly(ether imide) (PEI) and poly(lactic-co-glycolic acid) (PLGA) as surface coating polymers for WE43 Mg-alloy stent. Using a sequential spray-coating method, we developed a novel asymmetric stent coating comprising an inner surface coated with a PEI single layer and outer/side surfaces coated with sirolimus-loaded PLGA/PEI double layers. PEI coating layer has excellent adhesiveness to WE43 surface and considerably improves WE43 corrosion resistance and in vitro endothelial cell compatibility. PLGA/PEI double coating layer ensures a low release rate of sirolimus and stable surface morphology during drug-release process. Only vascular smooth muscle cells are directly affected by sirolimus owing to the asymmetric geometry of PLGA/PEI double coating, which has a satisfactory anti-proliferation effect. These results indicate that the developed asymmetrically PEI- and PLGA/PEI-coated WE43 stents have significant potential for achieving enhanced re-endothelialization and suppressed in-stent restenosis in vascular stent applications.

Efficacy and safety of drug-eluting stent for the intracranial atherosclerotic disease: A systematic review and meta-analysis

Drug-eluting stent (DES) is a potential endovascular treatment for patients with symptomatic intracranial atherosclerotic disease (sICAD). However, evidence regarding the treatment of ICAD with DES is lacking. We systematically searched Pubmed, Embase, Cochrane database (before 2017-12-21) for literature reporting the application of DES in the treatment of sICAD. The main outcomes were as follows: the incidence of any stroke or death within 30 days (perioperative complications), ischemic stroke in the territory of the qualifying artery beyond 30 days (long-term complications), in-stent restenosis rate (ISR) and symptomatic ISR during follow-up. Those studies with mean stenosis rate greater than 70% and less than 70% were defined as severe and moderate stenosis group, respectively. The random effect model was used to pool the data. Of 518 articles, 13 studies were eligible and included in our analysis (N = 336 patients with 364 lesions). After the implantation of DES, perioperative complications (mortality = 0) occurred in 6.0% (95%CI 2.0%–11.9%), long-term complications occurred in 2.2% (95%CI 0.7%–4.5%), ISR rate was 4.1% (95%CI 1.6%–7.7%) and the symptomatic ISR rate was only 0.5% (95%CI 0–2.2%). In addition, subgroup analysis showed that the perioperative complication rate in severe stenosis group [10.6% (95%CI 6.5%–15.7%)] was significantly (p < 0.01) higher than that in moderate stenosis group [1.0% (95%CI 0.3%–3.5%)]. In summary, endovascular DES implantation is a relatively safe and effective method compared with stents or medical management group in SAMMPRIS and VISSIT trials. However, a higher preoperative stenosis rate may imply a higher risk of perioperative complications. Further studies are needed.

Porous ZnO/2–Hydroxyethyl Methacrylate Eluting Coatings for Ureteral Stent Applications

High-surface-area porous coatings represent an interesting option to fabricate eluting stents with additional functionalities, as controlled drug delivery and antibacterial resistance properties. ZnO is a biocompatible material available in various high-surface-area morphologies, with promising antibacterial properties. Hydrophilic 2-hydroxyethyl methacrylate (HEMA) polymers (pHEMA) have been widely investigated for their biomedical applications, thanks to their biocompatibility, absence of toxicity, and tunable swelling properties. This work aims to demonstrate the use of porous ZnO/polymer bilayer coatings for future drug eluting stent applications. Sputtered mesoporous ZnO layers were coated with pHEMA and p(HEMA-co-acrylic acid (AA)) films through vacuum infiltration and drop-casting methods. The last approach was found to be the most suitable one for achieving a good polymer infiltration within the ZnO matrix and to avoid the mechanical detachment of the porous film from the substrate. The corresponding release properties were evaluated by loading a fluorescent dye in the host ZnO matrix, before drop-casting the polymer coating. For pure ZnO, the release of the dye was completed after 2 h. For ZnO/pHEMA, the sustained release of the molecule was achieved with only 30% released after 2 h and 100% released after seven days. In this case, the pH-triggered delivery properties were also demonstrated by switching from neutral to acidic pH conditions. No significant changes were obtained for the ZnO/p(HEMA-co-AA) system, which exhibited a faster swelling behavior and a release profile similar to pure ZnO.

Treatment Of A Rare Vascular Complication Of Coronary Stenting In An Octagenarian

The ability of drug-eluting stent (DES) to inhibit intimal proliferation has resulted in a massive increase in their usage over the years. However, it is known that the application of DES can alter the normal cascade of vascular healing, resulting in delayed endothelialisation with risk of vascular complications. Coronary artery aneurysms (CAN) are defined as more than 50% dilatation of the coronary artery compared to the reference vessel diameter with the reported incidence after percutaneous intervention (PCI) being only around 0.35 to 6.0%. Previously, CAN had been reported with the use of bare metal stent secondary to stretch, stent fracture and dissection. However, recently, increasing number of cases have been reported describing CAN after DES implantation. To the best of the authors' knowledge, they present the first case from Pakistan of a left anterior descending coronary artery aneurysm after DES implantation treated successfully with stenting under intravascular ultrasound guidance.

OP126 Shared Decision-Making Influences Patients’ Adoption Of Stents In China

Introduction:Shared decision-making (SDM) is an essential component of patient-centered care, involving communication and discussions between physicians and patients on various options to meet their health needs. This study examines the current situation of patients’ participation in decision-making in relation to the clinical application of drug-eluting stents (DES). Further, the impact of patients’ involvement in decision-making on patients' adoption of DES was analyzed, with a view to providing research outcomes to guide clinical practice.Methods:A cross-sectional study was conducted from July to December 2016 in selected hospitals in Fujian Province, Sichuan Province, and Shanghai in China. Patients with coronary heart disease completed a survey, which contained the 9-item Shared Decision-Making Questionnaire (SDM-Q-9) about satisfaction with decision-making processes, and questions on DES. Data were analyzed with cluster analysis, correlation analysis, multivariate logistic regression, and multivariate linear regression.Results:One hundred and seventy-nine patients with coronary heart disease from 15 hospitals in the three regions completed the questionnaire. There were good validity and reliability for SDM-Q-9, with Cronbach's alpha as 0.96 and intra-class correlations 0.59–0.79 (all P &lt; 0.01). Among these respondents, 42.1 percent adopted DES, 83.4 percent were supportive of SDM and 61.33 percent thought they had better communication with physicians regarding decision-making. Patients’ level of SDM involvement was found to be positively associated with their satisfaction with the decision-making process (P &lt; 0.001) and their adoption of DES (P &lt; 0.05). Also, satisfaction with shared decision-making regarding treatment was positively associated with adoption of DES (P &lt; 0.001).Conclusions:Most of the patients with coronary heart disease preferred SDM, and SDM was found to be an important predictor of patients’ satisfaction with decision-making processes and adoption of DES. Better communication between physicians and patients is needed in order to improve patients’ satisfaction and promote the appropriate use of DES technology in China.

Evaluation of chemical stability of polymers of XIENCE everolimus-eluting coronary stents in vivo by pyrolysis-gas chromatography/mass spectrometry.

The polymers poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) and poly(n-butyl methacrylate) (PBMA) are employed in manufacturing the XIENCE family of coronary stents. PBMA serves as a primer and adheres to both the stent and the drug coating. PVDF-HFP is employed in the drug matrix layer to hold the drug everolimus on the stent and control its release. Chemical stability of the polymers of XIENCE stents in the in-vivo environment was evaluated by pyrolysis-gas chromatography with mass spectrometry (Py-GC/MS) detection. For this evaluation, XIENCE stents explanted from porcine coronary arteries and from human coronary artery specimens at autopsy after 2-4 and 5-7 years of implantation, respectively, were compared to freshly manufactured XIENCE stents (controls). The comparison of pyrograms of explanted stent samples and controls showed identical fragmentation fingerprints of polymers, indicating that PVDF-HFP and PBMA maintained their chemical integrity after multiple years of XIENCE coronary stent implantation. The findings of the present study demonstrate the chemical stability of PVDF-HFP and PBMA polymers of the XIENCE family of coronary stents in the in-vivo environment, and constitute a further proof of the suitability of PVDF-HFP as a drug carrier for the drug eluting stent applications. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1721-1729, 2018.

Novel Poly(Diol Sebacate)s as Additives to Modify Paclitaxel Release From Poly(Lactic-co-Glycolic Acid) Thin Films

Paclitaxel (PTX) incorporation in poly(lactic-co-glycolic acid) (PLGA) matrices produce films with high tensile rigidity and slow release that fail to deliver the required release rate for most biomedical applications such as in drug eluting stents and cancer treatments. To modify and improve this behavior, a set of poly(diol sebacate)s were synthesized and fully characterized as possible additives. The tensile properties of PLGA blends were evaluated as these materials could be used as coatings in drug eluting stent applications. A significant improvement in mechanical flexibility was observed with 20% additive content, as it reduced the Young’s modulus value and increased the maximum deformation at break. PTX release was studied and correlated with the release of additive from PLGA films. An increase in the initial burst release phase was observed on all blends when compared to the control films of PLGA. Modulation of PTX release was achieved by altering the hydrophilicity degree of the additive or its percentage content on the blend. This supports the possibility that PTX was partitioned into the additive phase. Cytotoxicity analyses of novel additives were performed on mouse embryonic fibroblasts NIH/3T3.

Preparation of paclitaxel/chitosan co-assembled core-shell nanofibers for drug-eluting stent

The paclitaxel/chitosan (PTX/CS) core-shell nanofibers (NFs) are easily prepared by co-assembly of PTX and CS and used in drug-eluting stent. The mixture solution of PTX (dissolved in ethanol) and CS (dissolved in 1% acetic acid water solution) under sonication will make the formation of NFs, in which small molecule PTX co-assembles with biomacromolecular CS through non-covalent interactions. The obtained NFs are tens to hundreds nanometers in diameter and millimeter level in length. Furthermore, the structure of PTX/CS NFs was characterized by confocal laser scanning microscopy (CLSM), zeta potential, X-ray photoelectron spectroscopy (XPS) and nanoscale infra-red (nanoIR), which provided evidences demonstrated that PTX/CS NFs are core-shell structures. The ‘shell’ of CS wrapped outside of the NFs, while PTX is located in the core. Thus it resulted in high drug loading content (>40wt.%). The well-controlled drug release, low cytotoxicity and good haemocompatibility were also found in drug carrier system of PTX/CS NFs. In addition, the hydrophilic and flexible properties of NFs make them easily coating and filming on stent to prepare drug-eluting stent (DES). Therefore, this study provides a convenient method to prepare high PTX loaded NFs, which is a promising nano-drug carrier used for DES and other biomedical applications. The possible molecular mechanism of PTX and CS co-assembly and core-shell nanofiber formation is also explored. Statement of significanceWe develop a convenient and efficient approach to fabricate core-shell nanofibers (NFs) through the co-assembly of paclitaxel (PTX) and chitosan (CS). Results indicate that the co-assembled PTX/CS NFs have high drug loading content (>40wt.%), low cytotoxicity, well-sustained drug release and good haemocompatibility. The PTX/CS NFs coated easily on stents with substrate surface uneven and irregular. Findings from this work provide a novel drug/polymer system, which would have potential application for drug-eluting stent (DES).

Effect of solvent on drug release and a spray-coated matrix of a sirolimus-eluting stent coated with poly(lactic-co-glycolic acid).

Sirolimus (SRL) release from the biodegradable poly(l-lactic-co-glycolic acid) (PLGA) matrix was investigated for the application of drug-eluting stents (DES). In particular, this study focused on whether various organic solvents affect the interaction between SRL and PLGA and the formation of microstructures during ultrasonic coating. The SRL-loaded PLGA coated by tetrahydrofuran or acetone showed a significant initial burst, whereas that from acetonitrile was constantly released during a period of 21 days. On the basis of these results, the interactions at the molecular level of SRL with the polymer matrix were estimated according to various organic solvents. Although the topographies of the coated surface were obviously different, the correlation between surface roughness and SRL release was very poor. Irrespective of organic solvents, FT-IR data showed significantly weak SRL-PLGA interactions. From the result of wide-angle X-ray diffraction, it was confirmed that SRL was dispersed in an amorphous state in the polymer matrix after ultrasonic coating. The glass-transition temperature was also influenced by organic solvents, resulting in a plasticizing effect. The particle size of SRL appeared to determine the release profile from the PLGA matrix, which was the combination of diffusion and polymer degradation at an SRL size of more than 800 nm and the Fickian release at that of less than 300 nm. Therefore, organic solvents can lead to a heterogeneous microstructure in the SRL-loaded PLGA matrix, which is at or near the surface, consisting of aggregated drug- and polymer-rich regions. It is expected that the drug release can be controlled by physicochemical properties of organic solvents, and this study can be used effectively for localized drug release in biomedical devices such as drug-eluting stents.

쾌속조형기법을 이용한 생분해성 스텐트용 메쉬필름의 약물방출거동 효과

약물방출 고분자 코팅 스텐트는 수술후 재협착을 획기적으로 줄였지만, 약물방출이 균일한 구조체를 제작하는 것이 어렵고 체내에 구조체를 영구적으로 남겨야 하는 부담을 여전히 가지고 있다. 이를 해결하는 방안으로 생분해성 고분자로 스텐트를 제작하는 방법들이 활발하게 연구되고 있다. 본 연구에서는 조형가공기술(solid freeform fabrication, SFF)의 하나인 쾌속조형기법(rapid prototyping technique)의 3차원 플로팅(3D plotting) 기술을 이용하여 파크리탁셀(PTX) 약물을 함유한 폴리카프로락톤(PCL) 3차원 구조체를 제작하였고, 생분해성 PCL 고분자로부터 PTX의 방출거동과 스텐트 제작 가능성을 고찰하였다. 약물을 포함한 구조체의 표면특성을 SEM으로 확인한 결과 굴곡이 자연스럽고 매끄러운 표면을 가지고 있었다. FTIR을 통해서 약물이 성공적으로 구조체에 포함되었음을 확인하였고, NMR과 HPLC를 통해서 PCL 구조체 중의 PCL함량과 PTX의 서서히 방출됨을 확인되었다. 또한 세포실험을 통해 구조체에서 방출된 약물이 생물학적으로 활성을 유지하고 있으며, 반복제작된 구조체에서도 균일한 활성의 약물이 방출됨을 확인하였다. 이와같은 쾌속조형기법을 이용하여 약물을 포함하는 구조체를 제작하고 분석함으로써, 생분해성 고분자 스텐트로서의 적용가능성을 제시하였다. Biodegradable drug-eluting stent has dual functions of supporting the lumen and treating internal tumor preventing the restenosis by releasing drug. In this study, the polycaprolactone (PCL) based three dimensional (3D) mesh loaded with paclitaxel (PTX) was presented by rapid prototyping (RP) technique of solid freeform fabrication (SFF) for biodegradable drug-eluting stent application. PCL has many advantageous properties such as good biocompatibility, good mechanical properties, and good drug permeability. PTX is widely used in the cancer treatment by inhibiting tumor cell proliferation. Analytical methods of HPLC and NMR were used for simultaneous quantification of PTX. Scanning electron microscopy (SEM) was performed to observe the architecture and morphologies of 3D mesh. The cytotoxicity assay results indicated released PTX's biological activity. This study provided that PCL based 3D mesh loaded with PTX by RP technique has great potential for biodegradable drug-eluting stent application.

Long term outcomes of intracoronary brachytherapy treatment in coronary artery disease: 7 years follow-up period

Background: We aimed to investigate the effects of brachytherapy, drug-eluting stent (DES) and bare metal stent (BMS) applications in the treatment of coronary artery disease, on five-year clinical outcomes and mortality. Methods: Two hundred and seventeen patients who were treated in our clinics between January 2000 and December 2003 with brachytherapy, DES, or BMS for both de novo and in-stent restenosis lesions were included in this cohort study. Of these 217 patients, 69 received brachytherapy, 80 were given BMS and 68 were given DES. The clinical outcomes of the patients during hospitalization and over a long-term follow-up were evaluated. Cardiovascular events, revascularizations and mortality rates were compared among the three groups over a five-year follow-up. Results: The mean age was 60.1±9.5 years in the brachytherapy group, 55.7±9.2 years in the BMS group, and 58.9±9.8 years in the DES group (p = 0.44). All-cause mortality rates were 20 (29%) brachytherapy patients, 22 (27.5%) BMS patients, and four (5.9%) DES patients (p = 0.01). Cardiovascular event was the cause of death for 14 (20.3%) brachytherapy patients, 16 (20%) BMS patients and four (5.9%) DES patients (p = 0.001). All-cause mortality rates were 20 (29%) brachytherapy patients, 22 (27.5%) BMS patients and four (5.9%) DES patients. All-cause and cardiovascular mortality rates were significantly lower in the DES group compared to both the BMS and the brachytherapy groups (p = 0.01 and p = 0.001, respectively) (Figure 1). ![Figure][1] Conclusions: DES application for in-stent restenosis and de novo lesions was superior to brachytherapy and BMS application with respect to all-cause and cardiovascular mortalities [1]: pending:yes

Impact of Artificial Plaque Composition on Drug Transport

Drug-eluting stent (DES) implantation is a common treatment for atherosclerosis. The safety and efficacy of these devices will depend on the uptake and distribution of drug into the vessel wall. It is established that the composition of atherosclerotic vessels can vary dramatically with patients' age and gender. However, studies focused on elucidating and quantifying the impact of these variations on important drug transport properties, such as diffusion (D) and partition (k) coefficients, are limited. We have developed an improved tissue mimic or artificial plaque to probe the effect of varying concentrations of plaque constituents on drug transport in vitro. Based on these artificial plaques, we have quantified the impact of gelatin (hydrolyzed collagen) and lipid (cholesterol) concentration on D and k using two model drugs, tetracycline and fluvastatin. We found that for tetracycline, increasing the collagen concentration from 0.025 to 0.100 (w/w) resulted in a fivefold decrease in diffusivity, whereas there was no discernible impact on solubility. Increasing the lipid concentration up to 0.034 (w/w) resulted in only minor changes to transport properties of tetracycline. However, fluvastatin exhibited nearly a fivefold increase in k and 10-fold decrease in D with increased lipid concentration. These results were in reasonable agreement with existing models and exhibited behavior consistent with previous observations on drugs commonly used in DES applications. These observations suggest that variations in the chemical characteristics of atherosclerotic plaque can significantly alter the release rate and distribution of drug following DES implantation.

Drug-eluting stents or coronary artery bypass grafting for unprotected left main coronary artery disease: a meta-analysis of four randomized trials and seventeen observational studies

BackgroundThe clinical application of drug-eluting stents (DES) or coronary artery bypass grafting (CABG) for unprotected left main coronary artery disease (ULMCAD) is still controversial. The purpose of this meta-analysis was to compare the safety and efficacy between DES and CABG for ULMCAD.MethodsDatabases of MEDLINE, EMBASE and the Cochrane Library were systematically searched.ResultsTwenty-one studies with 8,413 patients were included in this meta-analysis. The risk was lower in DES than in CABG groups at the early outcomes of death (risk ratio (RR): 0.49, 95% confidence interval (CI): 0.30–0.78), cerebrovascular events (RR: 0.19, 95% CI: 0.08–0.45) and composite endpoint (RR: 0.53, 95% CI: 0.40–0.70); death after 2 years (RR: 0.81, 95% CI: 0.66–0.99), 4 years (RR: 0.69, 95% CI: 0.53–0.90), 5 years (OR: 0.76, 95% CI: 0.61–0.95) and their total effect (RR: 0.79, 95% CI: 0.71–0.87); composite endpoint 1 year (RR: 0.69, 95% CI: 0.58–0.83), 4 years (RR: 0.69, 95% CI: 0.53–0.88), 5 years (RR: 0.74, 95% CI: 0.59–0.92) and their total effect (RR: 0.78, 95% CI: 0.71–0.85). There were no significant differences in the risk for the early outcomes of myocardial infarction (RR: 0.97, 95% CI: 0.68–1.38), death 1 year (OR: 0.81, 95% CI: 0.57–1.15) and 3 years (OR: 0.85, 95% CI: 0.69–1.04), composite endpoint of 2 years (RR: 0.88, 95% CI: 0.72–1.09) and 3 years (RR: 0.87, 95% CI: 0.73–1.04). Nonetheless, there was a lower risk for revascularization associated with CABG from 1 to 5 years and their total effect (RR: 3.77, 95% CI: 3.35–4.26). There was no difference in death, myocardial infarction, cerebrovascular events or revascularization at 1 year between RCT and observational groups.ConclusionsOur meta-analysis indicates that DES has higher safety but higher revascularization than CABG in patients with ULMCAD in the 5 years after intervention.

Porous TiO2 surface formed on nickel‐titanium alloy by plasma electrolytic oxidation: A prospective polymer‐free reservoir for drug eluting stent applications

In this study, a porous oxide layer was formed on the surface of nickel-titanium alloy (NiTi) by plasma electrolytic oxidation (PEO) with the aim to produce a polymer-free drug carrier for drug eluting stent (DES) applications. The oxidation was performed galvanostatically in concentrated phosphoric acid electrolyte at low temperature. It was found that the response of NiTi substrate during the PEO process was different from that of bulk Ti, since the presence of large amount of Ni delayed the initial formation of a compact oxide layer that is essential for the PEO to take place. Under optimized PEO conditions, the resultant surface showed porosity, pore density and oxide layer thickness of 14.11%, 2.40 × 10⁵ pores/mm² and 0.8 μm, respectively. It was additionally noted that surface roughness after PEO did not significantly increase as compared with that of original NiTi substrate and the EDS analyses revealed a decrease in Ni/Ti ratio on the surface after PEO. The cross-section morphology showed no discontinuity between the PEO layer and the NiTi substrate. Furthermore, wettability and surface free energy of the NiTi substrate increased significantly after PEO treatment. The PEO process could be successfully translated to NiTi stent configuration proving for the first time its feasibility for such a medical device and offering potential for development of alternative, polymer-free drug carriers for NiTi DES.

The edge vascular response following implantation of a fully bioresorbable device: ‘A miss always counts’

The application of drug-eluting stents (DES) and more recently that of bioresorbable scaffolds has tremendously reduced the rate of in-stent/ scaffold restenosis compared to conventional bare-metal stents (BMS) in the treatment of coronary artery disease. The use of radioactive stents during the transition from BMS to DES transiently eliminated the phenomenon of in-stent restenosis; however although brachytherapy was a reasonable solution the main pitfall of this treatment approach was the edge vascular response (EVR) or “candy–wrapper” effect [1]. Since then the EVR has been investigated with first generation DES short term (6-months) [2] and bioresorbable vascular scaffolds (BVS) midterm up to 1-year [3]. We demonstrate two selected cases of proximal edge stenosis resulting in target lesion revascularization as a consequence of geographical miss (GM) following implantation of the ABSORB BVS from the ABSORB Extend (Case 1) and ABSORB Cohort B trials (Case 2).