Coronary Stent Platforms Research Articles

Evolution of Coronary Stent Platforms: A Brief Overview of Currently Used Drug-Eluting Stents

Cardiovascular disease, including ischemic heart disease, is the leading cause of death worldwide, and percutaneous coronary interventions (PCIs) have been demonstrated to improve the prognosis of these patients on top of optimal medical therapy. PCIs have evolved from plain old balloon angioplasty to coronary stent implantation at the end of the last century. There has been a constant technical and scientific improvement in stent technology from bare metal stents to the era of drug-eluting stents (DESs) to overcome clinical challenges such as target lesion failure related to in-stent restenosis or stent thrombosis. A better understanding of the underlying mechanisms of these adverse events has led DESs to evolve from first-generation DESs to thinner and ultrathin third-generation DESs with improved polymer biocompatibility that seems to have reached a peak in efficiency. This review aims to provide a brief historical overview of the evolution of coronary DES platforms and an update on clinical studies and major characteristics of the most currently used DESs.

Complementary evidence on the performance of coronary stents generated by a randomized controlled trial and a worldwide registry

Large-scale registries can provide valuable complementary data to randomized controlled trials (RCT) for the postmarketing evaluation of coronary stents, but their scientific relevance remains debated. We sought to compare the evidence on the performance of a single coronary stent platform generated by the RCT for its regulatory approval and a well-conducted international registry. Patients treated with the Ultimaster coronary stent in the CENTURY II (CII-UM) trial (n=551) were compared to patients in the real-world e-ULTIMASTER (e-UM) registry (n=35,389). All major events were adjudicated by an independent clinical event committee in both studies. Propensity weighted analysis was used to balance baseline and procedural differences between the 2 populations. Coronary artery disease was more complex in e-UM compared to CII-UM, including more acute coronary syndromes, multivessel disease, left main, arterial, or venous grafts, and chronic total occlusions (P < .005 for all). At one-year follow-up and after excluding periprocedural myocardial infarction (MI) there was no statistically significant difference between CII-UM and e-UMregarding all-cause death (hazard ratio [HR] 0.55, 95% confidence interval [CI] 0.26-1.20, P=.14), cardiac death (HR 0.71, 95% CI 0.29-1.72, P=.45), target lesion failure (HR 1.18, 95% CI 0.78-1.78, P=.44), and target vessel MI (HR 0.76, 95% CI 0.24-2.38, P=.63). However, target vessel revascularization rate was significantly higher in CII-UM than in e-UM, HR 1.78, 95% CI 1.23-2.56, P=.002. A well-conducted large-scale registry can provide valuable complementary evidence to RCTs on the postmarket performance of new coronary stents, across a wider range of uses and various geographic areas.

The mega COMBO collaboration: An individual patient data pooled analysis of patients undergoing PCI with COMBO stent

BackgroundCOMBO (OrbusNeich Medical, Hong Kong) is a dual-therapy coronary stent featuring sirolimus as antiproliferative drug and an anti-CD34+ antibody coating to attract endothelial progenitor cells favoring rapid stent re-endothelization. The Mega COMBO collaboration aimed to evaluate the performance of the COMBO stent in a large contemporary cohort of patients undergoing percutaneous coronary intervention (PCI). MethodsPatient-level data of subjects undergoing PCI with the COMBO stent from the REMEDEE-Trial, REMEDEE-OCT, HARMONEE, REDUCE, SORT OUT X, REMEDEE-Registry and MASCOT studies were pooled together. The primary endpoint was 1-year target lesion failure (TLF), a composite of cardiovascular death, target vessel myocardial infarction (TV-MI) or clinically driven target lesion revascularization (CD-TLR). Secondary outcomes were the individual components of the primary endpoint and stent thrombosis (ST). Endpoints were evaluated against performance goals based on the EAPCI (the European Association of Percutaneous Coronary Intervention) recommendations for new drug-eluting stents. ResultsA total of 6753 patients (mean age 63.7 ± 11.4 years, 23% women) were included. At 1-year follow-up, TLF occurred in 303 (4.6%) patients. The rates of cardiovascular death, TV-MI, and CD-TLR were 1.3%, 1.8%, and 2.5%, respectively. The rate of definite/probable ST was 0.73%, early ST (<1 month) was 0.48%, while late ST (1–12 months) was 0.26%. The performance goals were met for all of the evaluated endpoints. ConclusionsThis large patient-level pooled analysis provides a comprehensive outline of the performance of the dual-therapy COMBO stent. The low rates of primary and secondary endpoints suggest that this stent technology may be a good alternative to other contemporary drug eluting coronary stent platforms.

Confirming the performance of new coronary stent platforms by systematic registry-based cluster-randomised evaluation of their implementation in clinical practice.

Confirming the performance of new coronary stent platforms by systematic registry-based cluster-randomised evaluation of their implementation in clinical practice.

Nanoparticle-eluting stents for coronary intervention: formulation, characterization, and in vitro evaluation.

Coronary artery disease (CAD) is currently a leading cause of death worldwide. In the history of percutaneous coronary intervention for the treatment of CAD, a drug-eluting stent (DES) is recognized as a revolutionary technology that has the unique ability to significantly reduce restenosis and provide both mechanical and biological solutions simultaneously to the target lesion. The aim of the research work was to design and fabricate DES coated with a nanoparticulate drug formulation. Sirolimus, an inhibitor of the smooth muscle cell (SMC) proliferation and migration, was encapsulated in polymeric nanoparticles (NPs). The NP formulation was characterized for various physicochemical parameters. Cell viability and cell uptake studies were performed using human coronary artery smooth muscle cells (HCASMCs). The developed NP formulation showed enhanced efficacy compared to plain drug solution and exhibited time-dependent uptake into the HCASMCs. The developed NP formulation was coated on the Flexinnium™ ultra-thin cobalt-chromium alloy coronary stent platform. The NP-coated stents were characterized for morphology and residual solvent analysis. In vitro drug release was also evaluated. Ex vivo arterial permeation was carried out to evaluate the NP uptake from the surface of the stents. The characterization studies together corroborated that the developed NP coated stent can be a promising replacement of the current DESs.

A Robustly Supported Extracellular Matrix Improves the Intravascular Delivery Efficacy of Endothelial Progenitor Cells

AbstractA major barrier in the multi‐purpose use of implantable materials is an incomplete integration with surrounding tissues, causing foreign body reactions, such as fibrous encapsulation and chronic inflammation. From its viewpoint, a universal method is suggested for cloaking any kind of substrate in specific cell‐made extracellular matrices (ECMs) via robust linkages for delivery of therapeutic cells. In addition, the feasibility of ECM‐coated substrates as endothelial progenitor cells (EPCs)‐laden coronary stent platform for endovascular implantation is investigated. Characteristics and stability of cell‐secreted ECMs anchored on a substrate are evaluated, and structural and componential features are revealed similar to those of native ECMs, with enough strength to enable practical uses. The in vitro experiments demonstrated that the ECM coating effectively supports the adhesion, proliferation, and viability of EPCs and has selectively opposite effects on smooth muscle cells. The in vivo experiments using a porcine coronary model supports that ECM‐coated stents enable endothelial regeneration and inhibit neointimal growth, and the cell‐laden form is more effective than other stents. These results will allow the preparation of tissue‐integrating materials containing cellular microenvironments and safely coat surfaces with cells to enable long‐term implantation and the continuous managing of chronic diseases.

Surrogate‐based multi‐objective design optimization of a coronary stent: Altering geometry toward improved biomechanical performance

The main objective of this study was to solve a multi-objective optimization on a representative coronary stent platform with the goal of finding new geometric designs with improved biomechanical performance. The following set of metrics, calculated via finite element models, was used to quantify stent performance: vessel injury, radial recoil, bending resistance, longitudinal resistance, radial strength and prolapse index. The multi-objective optimization problem was solved with the aid of surrogate-based algorithms; for comparison and validation purposes, four surrogate-based multi-objective optimization algorithms (EIhv -EGO, Phv -EGO, ParEGO and SMS-EGO) with a limited sample budget were employed and their results compared. The quality of the non-dominated solution sets outputted by each algorithm was assessed against four quality indicators: hypervolume, R2, epsilon and generational distance. Results showed that Phv -EGO was the algorithm that exhibited the best performance in overall terms. Afterwards, the highest quality Pareto front was chosen for an in-depth analysis of the optimization results. The amount of correlation and conflict was quantified for each pair of objective functions. Next, through cluster analysis, one was able to identify families of solutions with similar performance behavior and to discuss the nature of the existent trade-offs between objectives, and the trends between design parameters and solutions in a biomechanical perspective. In the end, a constrained-based design selection was performed with the goal of finding solutions in the Pareto front with equal or better performance in all objectives against a baseline design.

Abluminus DES+ for the treatment of coronary artery disease in patients with diabetes mellitus.

Diabetes mellitus (DM) is a rising global epidemic affecting more than 10% of the world population and predisposes patients to develop highly progressive and complex coronary artery disease. Despite numerous advancements in percutaneous coronary intervention procedural techniques and coronary stent platforms, clinical outcomes in DM patients have improved little compared with non-DM patients. Abluminus DES+, a biodegradable polymer sirolimus-eluting stent deployed with a drug-coated balloon, has been specifically designed to provide adequate coverage for DM patients and reduce adverse clinical outcomes.

The OPTIMIZE randomized trial to assess safety and efficacy of the Svelte IDS and RX Sirolimus-eluting coronary stent Systems for the Treatment of atherosclerotic lesions: Trial design and rationale

Coronary stenting without angioplasty pretreatment (direct stenting) may simplify procedures in appropriate lesions. Direct stenting is facilitated by smaller profile coronary stent platforms. The present study was designed for regulatory approval of a novel drug-eluting coronary stent and incorporates both randomized comparison for non-inferiority to an approved predicate device as well as a nested evaluation of subjects eligible for direct stenting. STUDY DESIGN AND OBJECTIVES: Prospective, single-blind, randomized, active-control, multi-center study designed to assess the safety and efficacy of the novel Svelte sirolimus-eluting stent (SES) systems. A total of 1630 subjects with up to 3 target lesions will be randomized 1:1 to the Svelte SES versus either the Xience or Promus everolimus-eluting stents (control). Randomization will be stratified by whether or not a direct stenting strategy is planned by the investigator. The primary endpoint is target lesion failure (TLF) at 12 months post index procedure, defined as cardiac death, target vessel myocardial infarction, or clinically driven target lesion revascularization, and the primary analysis is a non-inferiority test with a non-inferiority margin of 3.58%. Secondary clinical endpoints include individual components of TLF, stent thrombosis and measures of procedural resource utilization including contrast administration, fluoroscopy exposure and procedural resource utilization as well as costs. CONCLUSION: The OPTMIZE Trial will evaluate the safety, efficacy and clinical value of the novel Svelte SES in subjects with up to 3 lesions, and will provide a comparison of direct stenting between randomized devices.

Surrogate-based visualization and sensitivity analysis of coronary stent performance: A study on the influence of geometric design.

The main goal of this numerical study is to assess the impact of geometric design perturbations on the performance of a representative coronary stent platform. In this context, first, a design parameterization model was defined for the stent under study. After, a set of metrics characterizing stent performance, namely, vessel injury, radial recoil, bending resistance, longitudinal resistance, radial strength, the risk of fracture, prolapse index, and dogboning were evaluated within the context of a finite element analysis. Afterwards, accurate surrogate models were developed, using the efficient global optimization algorithm, as predictive tools in the execution of tasks that normally require a high number of model evaluations, such as global sensitivity analysis and visualization. In the end, the dependence of the output response surfaces on the geometric parameters was mechanically interpreted, which allowed us to understand the complex interplay that exists between the considered design variables and the defined performance metrics.

Abstract 387: Bioengineering L-605 Cobalt Chromium Cardiovascular Stent Biomaterial With Plasma Activated Coating, for Proactive Biocompatibility

Introduction: Cobalt Chromium alloy L605 is an underlying biomaterial in new generation drug eluting stents (DES) and bare metal stents (BMS). Suboptimal biocompatibility of stents clinically manifest as thrombosis and restenosis. We optimized a plasma coating technology to activate an alloy L605 surface for enhanced biofunctionalization. Objective: Alloy L605 flat metal surface modified with plasma activated coating (PAC), covalently binds tropoelastin (TE) in its bioactive state. In vitro studies were conducted to assess biocompatibility of modified PAC biomaterial compared to the bare metal alloy L605. Methods and Results: The initial water contact angle (Kruss contact angle analyser, DS10) of PAC was 44.4 0 ±3.40 and correlating surface energy computed with the Owens-Wendt-Rabel-Ström kinetic model was 62.35±2.4 mJ/m 2 . Thrombogenicity studies with heparinised whole blood (0.5 U/mL, 37 0 C), in a modified chandler loop showed significantly less clot formation at 60 mins for PAC, PAC+TE Vs. L605 surfaces; 2.2±1.01 mg, 3.6±0.85 mg and 10.3±3.26 mg respectively (P&lt;0.05). Static blood assays with platelet rich plasma (PRP) on PAC and PAC+TE surfaces were compared to L605 (figure 1). Samples incubated with tropoelastin and treated with SDS-Elisa (90 0 C, 10 mins), to assess covalent binding showed higher absorbance for PAC vs. L605. Robust adhesion of PAC polymer to L605 was quantified as surface element percentage with energy dispersive X-ray spectroscopy (2 kV, Xray 2000 cps). Future studies will be conducted on an alloy L605 coronary stent platform. Conclusion: The plasma coating is hydrophilic and hemocompatible. The PAC technology will be translated to a commercially available alloy L-605 coronary stent platform to establish a pre-clinical model of hemocompatibility in vitro, as an alternative to animal model testing. Early events of coagulation and inflammation will be determined via biological evaluation assays of medical devices (ISO 10993-4).

Clinical and biomechanical behavior of a platinum-cromium stent platform in a large all-comers single centre PCI population: insights from the Novara-PROMETEUS registry

Aims: Recent reports have described cases of longitudinal deformation in new generation thin-strut coronary stents and biomechanical analyses have suggested increased susceptibility for such a complication for the novel platinum chromium (PtCr) Elements™ coronary stent platform. The present study assesses the incidence of longitudinal stent deformation for PtCr stents in a large single centre all-comers population. Methods and results: Quantitative angiographic analysis (QCA) of 337 PtCr stents deployed in 253 consecutive all-comers patients treated in our Laboratory from January 2011 to August 2012 was performed. QCA: nominal stent length ratio (QCA:NSLR) was considered as surrogate estimate of longitudinal stent deformation. The risk profile of the studied population was high, with 265 lesion (75.3%) classified as ACC/AHA type B2/C. QCA:NSLR averaged 0.95±0.04 in the whole population. The small post-deployment reduction of stent length had no clinical relevance, with only 3 cases (0.9%) of trivial geographical miss which did not required further interventions. Plaque prolapsed, usually small and focal, through the stent struts was observed in 19 cases (5.6%). No case of typical concertina effect was observed, while in 3 cases (0.9%) a large prolapsed plaque mimicked longitudinal stent deformation. Minor grades of stent deformation were more common and correlated with tortuous and calcified lesions, as expression of great stent conformability. Actually blinded a posteriori re-examination of the angiograms corresponding to the 20 lowest and highest ratios did not identify any cases of severe stent deformation. Logistic regression analysis identified a significant correlation between the need for predilation and lower QCA:NSLR values, while postdilation independently predicted higher QCA:NSLRs. Conclusions: Systematic QCA analysis of a large single centre population of all-comer PCI patients treated with PtCr stents failed to detect clinically relevant longitudinal stent deformations. Need for predilation was associated with a reduced stent length ratio, even if this did not substantially influenced PCI outcomes. Conversely postdilation was associated with QCA stent measures closest to nominal. (Clinicaltrials.gov ID: [NCT01759719][1]) [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01759719&atom=%2Fehj%2F34%2Fsuppl_1%2FP3017.atom

PCV42 - Hospital budget impact of readmission penalties and bundled payments: Potential impact of coronary stent platforms

PCV42 - Hospital budget impact of readmission penalties and bundled payments: Potential impact of coronary stent platforms

Risk-treatment paradox in women with symptomatic coronary artery disease

The implementation of evidence-based treatment including diagnostic and therapeutic invasive procedures has resulted in a reduction in the mortality attributable to coronary artery disease (CAD) despite the fact that patients at high risk are less likely to have access to it. Women in particular are up to 30 % less likely to receive percutaneous coronary intervention (PCI) following presentation with an acute coronary syndrome than men. This risk-treatment paradox for women is partially related to their older age, greater likelihood of comorbidities, and later presentation after symptom onset with more frequent atypical symptoms as well as to the higher proportion of symptomatic women having nonobstructive CAD. In addition, during the first decade of the PCI era, a poorer short-term survival after revascularization in women was reported while similar or better long-term outcomes than men was consistently observed. The subtly different spectrum of biological factors predisposing to high risk, frequent vascular complications, and high incidence of bleeding events, mostly related to the antithrombotic drugs over dosage, explain the early hazard seen in women. Newer antithrombotic regimens and the modern coronary stent platforms have contributed to drastic improvement of outcomes, particularly in high-risk subsets of patients including women. However, still more evidence from randomized trials with a representative proportion of women is required both to fully categorize CAD in women and to determine the most appropriate approach to therapy. Furthermore, physicians must continue to work to better identify high-risk patients and to tailor the evidence-based therapy to individual risk independent of patient’s sex.

Nickel-free stainless steel avoids neointima formation following coronary stent implantation

SUS316L stainless steel and cobalt–chromium and platinum–chromium alloys are widely used platforms for coronary stents. These alloys also contain nickel (Ni), which reportedly induces allergic reactions in some subjects and is known to have various cellular effects. The effects of Ni on neointima formation after stent implantation remain unknown, however. We developed coronary stents made of Ni-free high-nitrogen austenitic stainless steel prepared using a N2-gas pressurized electroslag remelting (P-ESR) process. Neointima formation and inflammatory responses following stent implantation in porcine coronary arteries were then compared between the Ni-free and SUS316L stainless steel stents. We found significantly less neointima formation and inflammation in arteries implanted with Ni-free stents, as compared to SUS316L stents. Notably, Ni2+ was eluted into the medium from SUS316L but not from Ni-free stainless steel. Mechanistically, Ni2+ increased levels of hypoxia inducible factor protein-1α (HIF-1α) and its target genes in cultured smooth muscle cells. HIF-1α and their target gene levels were also increased in the vascular wall at SUS316L stent sites but not at Ni-free stent sites. The Ni-free stainless steel coronary stent reduces neointima formation, in part by avoiding activation of inflammatory processes via the Ni-HIF pathway. The Ni-free-stainless steel stent is a promising new coronary stent platform.

Longitudinal deformation – Price we pay for better deliverability of coronary stent platforms

Coronary stents, especially drug eluting stents (DES), have revolutionized the practice of interventional cardiology. Newer stents are manufactured by altering basic design characteristics to tackle complex coronary morphologies more effectively. Alteration in one particular attribute might affect other attributes adversely. Even though, reduction in the number and alteration of the orientation of the connectors improves the stent flexibility and deliverability, it adversely decreases the axial strength of the stent with resulting longitudinal stent deformation. A 67 year old female underwent percutaneous coronary intervention for a mid left anterior descending artery stenosis with a 2.75 × 16 mm Promus Element stent (Boston Scientific, Natick, Massachusetts). The stent got longitudinally distorted during post-stent balloon dilatation which was effectively managed with further dilatation with non-compliant balloon.

Engineering assessment of the longitudinal compression behaviour of contemporary coronary stents

There have been recently reported clinical observations of significant longitudinal compression or "stent shortening" in certain contemporary drug-eluting stents (DES), when re-crossed with other devices such as post-dilatation balloons, stent delivery systems or intravascular ultrasound (IVUS) catheters. The aim of this study was to understand the effect of stent design on longitudinal compression for coronary stents, when subjected to certain forces in vitro. This goal was achieved by experimentally evaluating the longitudinal strength of 14 contemporary stent designs under a clinically relevant compression force using a bench test method developed for this purpose. The results from the study are intended to provide an indication whether there is a quantifiable difference in the ability of the different stent platform designs to resist longitudinal compression in a deployed configuration. A test method was developed to evaluate the longitudinal compression behaviour of coronary stents. The test method was used to compare the longitudinal compression of four stent design families including a total of 14 commercialised stent platforms under a clinically relevant longitudinal compression force. The nominal expansion diameter of stents used in this study was 3.0 mm with stent lengths ranging from 28-30 mm. A test method was also developed to estimate a value of the clinically relevant longitudinal compression force to which a deployed stent may be subjected in a situation when a catheter tip is caught while trying to cross a freshly deployed stent. That force was determined to be 50 gram force (gf) (0.49 N). Based on the results of the testing it was noted that three of the four design families (13 of the 14 stents tested) demonstrated a longitudinal compression in the range of 1.25-5.30 mm (longitudinal compression of 4.46%-18.93% compared to the nominal expanded stent length), with the exception of the offset peak-to-peak stent platform having results clearly outside of this grouping. The stent in the offset peak-to-peak design category (Element stent platform) had an average longitudinal compression of 13.20 mm (longitudinal compression of 47.07%), thus demonstrating a markedly lower resistance to longitudinal compression. Stent design is a primary driver determining the longitudinal compression behaviour of coronary stent platforms. The results of this study comparing the longitudinal compression performance of four different commercial stent design families indicate that the tendency of a deployed stent to undergo longitudinal compression is associated with the stent design concept. It was determined that the particular 2-link offset peak-to-peak design evaluated in this study had the lowest compression resistance compared to the other stent design families.

Longitudinal compression: a “new” complication with modern coronary stent platforms – time to think beyond deliverability?

Longitudinal compression: a “new” complication with modern coronary stent platforms – time to think beyond deliverability?

Periprocedural (30-day) risk of myocardial infarction after drug-eluting coronary stent implantation: a meta-analysis comparing cobalt-chromium and stainless steel drug-eluting coronary stents

Because of the reduction in the rate events related with in-stent restenosis, most events after drug-eluting stent implantation occur shortly after coronary stenting. Cobalt-chromium alloys allow to reduce strut thickness and improve flexibility and deliverability of coronary stent platforms, and thus could be associated with lower short-term events after stenting. The aim of this study was to test the hypothesis that drug-eluting coronary stents with a cobalt-chromium platform reduce the incidence of periprocedural (30-day) myocardial infarction in comparison with stainless steel drug-eluting coronary stents. A meta-analysis from nine randomised trials comparing cobalt-chromium and stainless steel drug-eluting coronary stents that overall included 11,313 patients was performed. The incidence of myocardial infarction, stent thrombosis, and cardiac death at 30 days was compared between both types of stents. At 30 days, the incidence of acute myocardial infarction was significantly lower in patients allocated to cobalt-chromium drug-eluting stents (2.3% vs. 3.9%, respectively; p=0.006; odds ratio 0.72, 95% confidence interval 0.58-0.91), due to a significant reduction in the rate of non-Q-wave myocardial infarction (odds ratio 0.67, 95% confidence interval 0.51-0.88). The incidence of stent thrombosis was similar between both groups of patients, (0.5% vs. 0.5%, p=0.76; odds ratio 1.09, 95% confidence interval 0.63-1.89). Drug-eluting coronary stents that use cobalt-chromium stent platforms have a better safety profile at 30 days in comparison with stainless steel drug-eluting stents, due to a significant reduction in the rate of myocardial infarction.

0838 心臓の収縮・拡張に伴うヒト右冠動脈基部の屈曲変形環境下での5種類のステントの破損に関する加速耐久試験(GS9:ステント)

0838 心臓の収縮・拡張に伴うヒト右冠動脈基部の屈曲変形環境下での5種類のステントの破損に関する加速耐久試験(GS9:ステント)