Next-generation Drug-eluting Stents Research Articles

Early vascular healing after neXt-generation drug-eluting stent implantation in Patients with non-ST elevation acute Coronary syndrome: a randomized optical coherence Tomography imaging study (EXPECT).

Early vascular healing after drug-eluting stent (DES) implantation is associated with better outcomes and lower incidence of in-stent thrombosis. To examine vascular healing response in patients with non-ST elevation acute coronary syndrome (NSTE-ACS) undergoing percutaneous coronary intervention (PCI) guided by optical coherence tomography (OCT) versus angiography alone. Sixty patients were randomized 1:1:1 to OCT-guided PCI with 3-month OCT follow-up (O3 group, n = 20), angiography-guided PCI with 3-month OCT follow-up (A3 group, n = 20), or angiography-guided PCI with 6-month OCT follow-up (A6 group, n = 20). The primary endpoint was the proportion of covered struts at 3- or 6-month follow-up. The proportion of covered struts in the O3 group was significantly higher than in the A3 group (95.2% vs. 92.3%, p < 0.001), but lower than in the A6 group (95.2% vs. 97.4%, p < 0.001). The O3 group had a lower proportion of incomplete strut apposition (ISA) than the A3 group (0.46% vs. 0.76%, p = 0.006), and higher than the A6 group (0.46% vs. 0.27%, p = 0.018) at follow-up. The optimal cut-off value of ISA after implantation of DES for predicting stent coverage at 3 and 6-month follow-up was 200μm and 308μm, respectively. Only one patient experienced target lesion revascularization in the A3 group during a 3-year clinical follow-up. In patients with NSTE-ACS undergoing PCI with DES, OCT guidance achieved higher strut coverage compared with angiography guidance at 3-month follow-up. However, the difference in the strut coverage between the OCT-guided group and the angiography-guided group at 6 months indicates that the degree of endothelialization may be more time-dependent instead of invasive device guidance.

Recent Advancements in Drug-Eluting Stents: A Comprehensive Review

Drug-eluting stents (DES) have revolutionized the field of interventional cardiology by significantly reducing restenosis rates compared to bare-metal stents (BMS). Over the past two decades, there have been remarkable advancements in DES technology aimed at improving efficacy, safety, and long-term outcomes. This comprehensive review provides an overview of recent developments in DES design, drug formulations, coatings, and delivery systems. It discusses the clinical evidence supporting the efficacy and safety of next-generation DES and explores emerging strategies to address remaining challenges, such as late stent thrombosis and neo atherosclerosis. Additionally, the paper examines future directions in DES research, including bioresorbable stents, drug-free coatings, and personalized approaches to stent selection.

Short-term (1-3 months) versus standard (12 months) dual antiplatelet therapy following new-generation drug-eluting stent implantation: A meta-analysis of randomized controlled trials.

Patients undergoing percutaneous coronary intervention mainly receive antiplatelet therapy. However, limited data are available regarding the optimal dual antiplatelet therapy (DAPT) following the implantation of new-generation drug-eluting stent (DES). This study aimed to compare the clinical outcomes of short-term (1-3 months) DAPT and standard (12 months) DAPT after the implantation of a new-generation of DES. We systematically searched PubMed, The Cochrane Library Database, Embase for trials that compared short-term (1-3 months) and standard DAPT after the implantation of next-generation DES were retrieved from all published studies in English until December 31, 2021. The primary endpoint was major bleeding. The secondary endpoints included all-cause mortality, cardiac death, myocardial infarction, stroke, stent thrombosis, and all bleeding. This study included a total of 7 randomized controlled trials, comprising 28,344 subjects. Regarding primary endpoints, short-term DAPT exhibited a significantly lower incidence of major bleeding compared with standard DAPT [relative risk (RR): 0.66, 95% confidence interval (CI): (0.54, 0.81), P < .0001]. For secondary endpoints, there were significant differences between short-term and standard DAPT in all bleeding [RR: 0.59, 95% CI: (0.50, 0.69), P < .00001]. However, no significant differences were identified in all-cause mortality [RR: 0.96, 95% CI: (0.77, 1.18), P = .27], myocardial infarction [RR: 0.98, 95% CI: (0.82, 1.18), P = .86], cardiac death [RR: 0.83, 95% CI: (0.63, 1.10), P = .20], stroke [RR: 1.08, 95% CI: (0.79, 1.47), P = .63], cerebrovascular [RR: 1.08, 95% CI: (0.79, 1.47), P = .63], and stent thrombosis [RR: 1.13, 95% CI: (0.80, 1.57), P = .49] between the 2 groups. In patients undergoing implantation of a new-generation of DES, short-term (1-3 months) DAPT exhibited no inferiority compared with standard (12 months) DAPT in terms of all-cause mortality, cardiac death, myocardial infarction, stroke, and definite or probable stent thrombosis compared with standard (12 months) DAPT. However, short-term DAPT appeared superior to standard DAPT in terms of major bleeding and all bleeding.

Biodegradable Polymer Versus Polymer-Free Ultrathin Sirolimus-Eluting Stents: Analysis of the Stent Arm Registry From the HOST-IDEA Randomized Trial.

The efficacy and safety of each third-generation drug-eluting stent with ultrathin struts and advanced polymer technology remain unclear. We investigated the clinical outcomes of percutaneous coronary intervention using the Coroflex ISAR polymer-free sirolimus-eluting stent (SES) or Orsiro biodegradable polymer SES. The HOST-IDEA trial (Harmonizing Optimal Strategy for Treatment of Coronary Artery Stenosis-Coronary Intervention With Next-Generation Drug-Eluting Stent Platforms and Abbreviated Dual Antiplatelet Therapy), initially designed with a 2×2 factorial approach, sought to randomize patients undergoing percutaneous coronary intervention based on dual antiplatelet therapy duration (3 versus 12 months) and stent type (Coroflex ISAR versus Orsiro). Despite randomizing 2013 patients for dual antiplatelet therapy duration, the stent arm transitioned to a registry format during the trial. Among these, 328 individuals (16.3%) were randomized for Coroflex ISAR or Orsiro SES, while 1685 (83.7%) underwent percutaneous coronary intervention without stent-type randomization. In this study, the Coroflex ISAR (n=559) and Orsiro groups (n=1449) were matched using a propensity score. The prespecified primary end point was target lesion failure, a composite of cardiac death, target vessel myocardial infarction, and clinically driven target lesion revascularization at 12 months. The baseline patient and procedural characteristics were well balanced between the Coroflex ISAR and Orsiro groups after propensity score matching (n=559, each group). The Coroflex ISAR group was significantly associated with a higher rate of target lesion failure, mainly driven by clinically driven target lesion revascularization, compared with the Orsiro group (3.4% versus 1.1%; hazard ratio, 3.21 [95% CI, 1.28-8.05]; P=0.01). A higher risk of target lesion failure in the Coroflex ISAR group was consistently observed across various subgroups. The rates of any bleeding (hazard ratio, 0.85 [95% CI, 0.51-1.40]; P=0.52) and major bleeding (hazard ratio, 1.58 [95% CI, 0.61-4.08]; P=0.34) were comparable between the 2 groups. In this propensity score-matched analysis of the stent arm registry from the HOST-IDEA trial, the Orsiro SES was associated with significantly better outcomes in terms of 1-year target lesion failure, mainly driven by clinically driven target lesion revascularization, than the Coroflex ISAR SES. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02601157.

One-year Outcomes of XIENCE Skypoint 48-mm Drug-Eluting Stents in Long Coronary Lesions: The SPIRIT 48 Trial.

Diffuse coronary artery disease may need multiple overlapping stents, associated with less favorable outcomes than those of a single stent. The availability of longer stents can circumvent the need for overlapping stents in long lesions. This prospective, single-arm, SPIRIT 48 trial evaluated the safety and effectiveness of Abbott's next-generation drug-eluting stent, XIENCE Skypoint 48, in patients with coronary artery disease with long de novo native coronary lesions. SPIRIT 48 enrolled 107 patients at 25 sites in 3 countries. Patients were required to have 1 target lesion treated with XIENCE Skypoint 48 (lesion length of >32.0 mm and ≤44.0 mm). The primary end point was target lesion failure (TLF; composite of cardiac death, target vessel-related myocardial infarction, or clinically indicated target lesion revascularization) at the 1-year compared with a prespecified performance goal of 20%, established through historical control data. This study recently completed its 1-year follow-up. XIENCE Skypoint 48 was implanted in 105 patients with a device success rate of 97.2%. SPIRIT 48 met its primary end point, with a TLF rate of 5.7%, and the upper bound of 95% CI at 9.5% (<performance goal of 20%). This was associated with a low rate of 5.8% (6/104 patients) for cardiac death/all myocardial infarction at 1 year. Definite or probable device thrombosis at 1 year occurred in only 1 subject (1.0%). Primary end point data obtained at the 1-year follow-up from the SPIRIT 48 trial present strong evidence supporting the deliverability, safety, and effectiveness of XIENCE Skypoint 48 mm drug-eluting stent in treating long de novo coronary lesions.

Early vascular healing after neXt-generation drug-eluting stent implantation in Patients with non-ST Elevation acute Coronary syndrome based on optical coherence Tomography guidance and evaluation (EXPECT): study protocol for a randomized controlled trial.

There is limited evidence about vessel wall healing response following implantation of next-generation drug-eluting stents (DES) in patients admitted with a non-ST elevation acute coronary syndrome (NSTE-ACS). Cumulative data indicate that optical coherence tomography (OCT) imaging can optimize percutaneous coronary intervention results and expedite stent endothelialization in the general population but there is lack of data in NSTE-ACS patients. The EXPECT study is an investigator-initiated, prospective, randomized trial to assess early vascular healing response following next-generation DES implantation in patients admitted with NSTE-ACS based on OCT guidance and evaluation. Sixty patients are randomized at 1:1:1 ratio to OCT-guided percutaneous coronary intervention (PCI) with 3-month follow-up OCT imaging (O3 group, n = 20), to angiography-guided PCI with 3-month follow-up OCT imaging (A3 group, n = 20) and to angiography-guided PCI with 6-month follow-up OCT imaging (A6 group, n = 20). The primary endpoint of the study is stent strut coverage rate at 3- or 6- month follow-up in the studied groups. The secondary endpoints of the study include OCT imaging endpoints, clinical endpoints, and molecular biology endpoints at the different time points. The clinical endpoints comprised of major cardiovascular adverse events and individual components. The molecular biology endpoints comprised of lipid levels and the levels of inflammatory indicators. The findings of the EXPECT study are anticipated to provide novel insights into vessel wall healing in NSTE-ACS population following implantation of next-generation DES, underscore the value of OCT imaging in expediting strut coverage in this setting, and explore the potential of an early discontinuation of dual antiplatelet therapy (DAPT) in this population. ClinicalTrials.gov, NCT04375319.

Study protocol for a randomised controlled trial: harmonising optimal strategy for treatment of coronary artery stenosis — coronary intervention with next-generation drug-eluting stent platforms and abbreviated dual antiplatelet therapy (HOST-IDEA) trial

IntroductionWe have recently seen the introduction of newer generation drug-eluting stents with ultrathin struts that use advanced polymer technologies. However, the efficacy and safety of these newest stents have not...

Stent-mediated gene and drug delivery for cardiovascular disease and cancer: A brief insight.

This review concisely recapitulates the different existing modes of stent-mediated gene/drug delivery, their considerable advancement in clinical trials and a rationale for other merging new technologies such as nanotechnology and microRNA-based therapeutics, in addition to addressing the limitations in each of these perpetual stent platforms. Over the past decade, stent-mediated gene/drug delivery has materialized as a hopeful alternative for cardiovascular disease and cancer in contrast to routine conventional treatment modalities. Regardless of the phenomenal recent developments achieved by coronary interventions and cancer therapies that employ gene and drug-eluting stents, practical hurdles still remain a challenge. The present review highlights the limitations that each of the existing stent-based gene/drug delivery system encompasses and therefore provides a vision for the future with respect to discovering an ideal stent therapeutic platform that would circumvent all the practical hurdles witnessed with the existing technology. Further study of the improvisation of next-generation drug-eluting stents has helped to overcome the issue of restenosis to some extent. However, current stent formulations fall short of the anticipated clinically meaningful outcomes and there is an explicit need for more randomized trials aiming to further evaluate stent platforms in favour of enhanced safety and clinical value. Gene-eluting stents may hold promise in contributing new ideas for stent-based prevention of in-stent restenosis through genetic interventions by capitalizing on a wide variety of molecular targets. Therefore, the central consideration directs us toward finding an ideal stent therapeutic platform that would tackle all of the gaps in the existing technology.

Duration of dual antiplatelet treatment in the era of next generation drug-eluting stents.

Current percutaneous coronary intervention guidelines recommend dual antiplatelets (aspirin 100 mg + clopidogrel 75 mg daily) for at least 12 mo following drug-eluting stent (DES) implantation if patients are not at high risk of bleeding. Several reports have tried to shorten the dual antiplatelet therapy to 3-6 mo, especially following next-generation DES implantation, for cost-effectiveness. However, the clinical results are inconsistent and the data regarding next-generation DESs limited. In this report, recently published important pivotal reports regarding the optimal duration of dual antiplatelets following DES implantation are summarized.

Smooth muscle-specific drug targets for next-generation drug-eluting stent

The occurrence of stent thrombosis is one of the major obstacles limiting the long-term clinical efficacy of percutaneous coronary intervention. The anti-smooth muscle proliferation drugs coated on drug-eluting stents (DES) often indistinguishably block re-endothelialization, an essential step toward successful vascular repair, due to their nonspecific effect on endothelial cells (ECs). Therefore, identification of therapeutic targets that differentially regulate vascular smooth muscle cell (VSMC) and EC proliferation may lead to the development of ideal drugs for the next-generation DES. Our recent studies have shown that CTP synthase 1 (CTPS1) differentially regulates the proliferation of VSMC and EC after vascular injury. Therefore, CTPS1 inhibitors are promising agents for DES. In addition to CTPS1, other factors have also shown cell-specific effects on VSMC and/or EC proliferation and thus may become potential molecular targets for developing drugs to coat stents.

The resolute™ integrity zotarolimus-eluting stent in coronary artery disease: a review.

The introduction of first-generation drug-eluting stents (DES) was a major advance in the percutaneous treatment of coronary artery disease, with DES significantly reducing the incidence of restenosis and major adverse coronary events compared with bare metal stents. Next-generation DES now utilizes lower profiles, thinner struts, and other technological advances to help extend their safety and efficacy. Importantly, studies of next-generation devices have now gone beyond controlled clinical trials with selected populations to registries and studies with all-comer populations, where more diverse and complex sets of patients and lesions have been managed. Thus, a large body of evidence and comparative data about the safety and efficacy of these devices has accumulated. The Resolute™ zotarolimus-eluting stent (R-ZES; Medtronic Inc., Santa Rosa, CA, USA) is a next-generation DES that uses a novel biocompatible polymer on a cobalt alloy stent platform to extend the duration of drug elution and improve the stent’s efficacy. The Integrity™ platform (Medtronic, Inc., Santa Rosa, CA, USA) used in the most recent iteration of the R-ZES stent further enhances the flexibility and deliverability of the stent in complex lesions by incorporation of a continuous sinusoidal design. In the following review, the clinical data is critically examined for the R-ZES and discuss its performance using comparative data currently available for next-generation DES. It is concluded that R-ZES use in complex patients and lesions is associated with durable efficacy and safety and represents another generational improvement in DES technology, which undoubtedly will enhance patient outcomes postpercutaneous coronary interventional.

Translational research on novel drug-eluting stents in percutaneous coronary intervention

Although first-generation drug-eluting stents (DES) have markedly reduced restenosis, complications of late and very late in-stent thrombosis have emerged as prime limitations to this technology. The development of new DES is a key process to prevent these complications. Translational research plays a very important role in experiments which determine the safety and efficacy of DES before human clinical trials. The present review focuses on translational research of novel DES, including drug discovery, creation of preclinical research models, planning and conducting of first-in-man studies, and developing next-generation DES systems.

A novel polymer‐free paclitaxel‐eluting stent with a nanoporous surface for rapid endothelialization and inhibition of intimal hyperplasia: Comparison with a polymer‐based sirolimus‐eluting stent and bare metal stent in a porcine model

Hypersensitivity and inflammatory responses to polymers may be responsible for late stent thrombosis after implantation of a drug-eluting stent (DES). Polymer-free DES may reduce the prevalence of these adverse reactions in vessels. We evaluated a polymer-free paclitaxel-eluting-stent with a nanoporous surface (nano-PES) for endothelialization and inhibition of neointimal hyperplasia by optical coherence tomography (OCT) and pathology in a porcine model. Nano-PES with high-dose (HD) and low-dose (LD) paclitaxel (1.0 μg/mm(2) and 0.4 μg/mm(2), respectively) was compared with a sirolimus-eluting stent (SES) and bare-metal stent (BMS) in a porcine model. Fifty-three stents (14 HD, 14 LD, 14 SES, 11 BMS) were implanted in 18 minipigs. At 14 days, nano-PES with HD and LD showed more complete endothelialization compared with SES. BMS had 100% endothelial coverage. At 28 days, a significant reduction in neointimal hyperplasia was detected by OCT in the nano-PES HD group compared with BMS. No benefit in prevention of the neointimal hyperplasia was observed in the nano-PES LD group. Nano-PES stents showed decreased deposition of fibrin and inflammation compared with SES. Pharmacokinetic studies revealed that nano-PES could effectively deliver the drug to the local coronary artery and it released the drug more rapidly than SES. Such a release profile was favorable for rapid endothelialization of nano-PES. The present study showed the nano-PES to be a new drug-delivery technology; that it used a nanoporous stent surface; that it offered desirable drug-elution properties without the use of polymers; that it may translate into an improved safety profile for next-generation DES.

New Drug-Eluting Stents

Drug-eluting stents (DES)were primarily conceived to reduce in-stent neointimal formation and therefore minimize the occurrence of restenosis, the major drawback of percutaneous coronary interventions with bare-metal stents (BMS). The development of DES has been pioneered through a combination of the increased understanding of the biology of restenosis, the selection of drugs that target 1 or more pathways in the restenotic process, controlled-release drug delivery strategies, and the use of the stent as a delivery platform. Although first-generation DES Cypher (sirolimus-eluting stent; Cordis Corporation, Johnson & Johnson, Warren, NJ) and Taxus (paclitaxel-eluting stent; Boston Scientific Corporation, Natick, Mass) have effectively achieved their main goal, reducing restenosis across virtually all lesion and patient subsets, their safety has been limited by suboptimal polymer biocompatibility, delayed stent endothelialization leading to late and very late thrombosis, and local drug toxicity.1,–,9 Both Cypher and Taxus use durable thick polymers to carry and control the release of their antiproliferative agents. The permanent presence of these polymers has been correlated to inflammatory responses and local toxicity in preclinical analysis.10,–,13 Furthermore, durable polymers used in first-generation DES have been associated with mechanical complications (eg, polymer delamination and “webbed” polymer surface leading to stent expansion issues)14 and nonuniform coating resulting in erratic drug distribution. As a consequence, in recent years, the focus of clinical research has been on the development of novel drug carrier systems including absorbable (or biodegradable) polymers and nonpolymeric stent surfaces. Additional improvements include the development of more modern platforms (eg, better deliverability, radiopacity, flexibility, and radial strength) as well as the use of novel antiproliferative agents or reduced doses of current approved antiproliferative drugs. This review focuses on describing next-generation drug-eluting stent systems based on the use of novel coatings and carrier systems developed to …

AS-157: Comparison of Zotarolimus-Eluting Stents with Sirolimus-Eluting and Paclitaxel-Eluting Stents for Patients with Diabetes Mellitus in the ZEST Trial: A Subanalysis of a Randomized Trial

Studies comparing the first-generation sirolimus- eluting stents (SES) and paclitaxel-eluting stents (PES) with the next-generation drug-eluting stents in the high-risk subgroup of patients with diabetes mellitus have been limited.

AS-152: Comparison of Zotarolimus-Eluting Stents with Sirolimus-Eluting and Paclitaxel-Eluting Stents for Coronary Revascularization in a Real-World Setting

Studies comparing the next-generation drug-eluting stents with first-generation sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES) for coronary revascularization in all-comers populations have been limited.

Controlling the drug release rate from biocompatible polymers with micro-patterned diamond-like carbon (DLC) coating

During the past year, we have witnessed the evolution of an intense public controversy regarding late thrombosis following implantation of drug eluting stent (DES) in patients with obstructive coronary artery disease. To overcome the problem, DES should possess sufficient biocompatibility and non-thrombogenicity with a controlled drug release system. A new DES composed of biocompatible polymers coated with antithrombogenic diamond-like carbon (DLC) coating was proposed. In this study, the drug release profile of the newly proposed drug eluting system was thoroughly investigated. Three polymers were selected as base drug-reservoir materials: hydrophilic 2-methacryloyloxyethyl phosphorylcholine (MPC), hydrophobic poly (ethylene-co-vinyl acetate) (EVA) and less hydrophobic polyurethane (PU). The three polymers are currently used or studied for biomedical materials, while MPC and DLC were already confirmed as excellent biocompatible materials with antithrombogenicity. After coating the lattice-like patterned DLC on both polymers containing drug, samples were soaked in 2 ml of medium of phosphate-buffered saline with 10% ethanol. The drug release rate was measured by a spectrophotometer. The percentile cover area of patterned DLC on polymers was varied from 0% (without DLC) to 100% (fully covered). The sample without DLC coating presented an initial burst of the drug release from the polymer matrix, whereas the DLC-coated samples inhibited the initial burst release from polymers within the first five days of the experiments. It was found that the drug eluting profiles could be effectively controlled by changing the cover area of micro-patterned DLC coatings on polymers, which may be applicable to the next-generation DES system that eventually prevents late thrombosis.

A review of current devices and a look at new technology: drug-eluting stents

Drug-eluting stents (DES) have become the standard of care for the treatment of coronary artery disease. However, late stent thrombosis has emerged as a major concern, especially in ‘off-label’ use. Pathologic studies of patients dying from late DES thrombosis demonstrate delayed arterial healing, characterized by persistent fibrin deposition and poor endothelialization as the primary substrate. Therefore, next-generation DES are being developed to increase the safety and biocompatibility by optimizing the three major components of DES: the stent platform, the polymer and the drug. Stents with thinner struts are endothelialized rapidly and cause less vessel-wall injury. Non-erodable polymers applied thinly and without defect or cracking cause less inflammation and will result in better long-term safety. Furthermore, use of biodegradable polymers, which fully degrade and leave a bare metal stent, will result in less inflammation. The choice of drug, dose and release kinetics should also be optimized. In addition to the improvement of DES components, new approaches, such as polymer-free drug delivery, prohealing approach and fully biodegradable stents, are emerging. Importantly, these technologies focus not only on efficacy but also on safety. The next-generation DES will probably be safer, with goals of improving endothelialization and more rapid arterial healing compared with first- and second-generation DES.

A pyrrole–imidazole polyamide targeting transforming growth factor-β1 inhibits restenosis and preserves endothelialization in the injured artery

Although the use of drug-eluting stents (DESs) has been shown to limit neointima hyperplasia, currently available DESs may adversely affect re-endothelialization. To evaluate whether a novel gene silencer pyrrole-imidazole (PI) polyamide targeting transforming growth factor (TGF)-beta1 is a candidate agent for the DESs, we examined the effects of PI polyamide targeting the TGF-beta1 promoter on neointimal formation in rat carotid artery after balloon injury. PI polyamide was designed to span the boundary of the AP-1 binding site of the TGF-beta1 promoter. After inducing balloon injury to arteries, incubation with PI polyamide was carried out for 10 min. Neointimal thickening and re-endothelialization were evaluated at 21 days after injury. Fluoresceinisothiocyanate-labelled PI polyamide was distributed into most of the nuclei in the injured artery without any delivery reagents. PI polyamide (100 microg) significantly inhibited neointimal thickening at 21 days after injury by 57%. PI polyamide targeting TGF-beta1 significantly decreased the expression of TGF-beta1 mRNA and protein in the artery at 3 days after injury and also suppressed the expression of connective tissue growth factor (CTGF), fibronectin, collagen type 1, and lectin-like ox-LDL receptor-1 mRNAs. A morphometric analysis showed that PI polyamide targeting TGF-beta1 accelerated re-endothelialization in the injured artery. These findings suggest that the synthetic PI polyamide targeting the TGF-beta1 promoter may have the potential to suppress neointimal hyperplasia after arterial injury by the down-regulation of TGF-beta1 and CTGF and the reduction of the extracellular matrix. As a result, PI polyamide targeting TGF-beta1 may therefore be a potentially effective agent for the treatment of in-stent restenosis, as a candidate agent for the next-generation DES.

Abstract 2553: Novel Cobalt-Chromium Ultra-Thin Strut Stent: Feasibility, Vascular Compatibility, and Safety Evaluation in Porcine Coronary Arteries

Stent-strut thickness is related to in-stent restenosis. Therefore, modern bare-metal stents (BMS) with lower strut thickness are in development. We sought to evaluate a new ‘third-generation’ BMS comprising an ultra-thin-strut, cobalt-chromium platform with fixed geometry and uniform cell sizes, in a clinically relevant animal model. 36 BMS of two types were implanted in pig coronaries using quantitative coronary angiography (QCA) to optimize stent apposition: a commercially available cobalt alloy thin-strut stent (91μm) as control (n=18), and an ultra-thin-strut (65μm) cobalt-chromium stent (Protea CoCr; n=18). Animals underwent angiographic restudy and termination 1-wk and 1-mo post-implant for coronary artery histology. In addition, 12 overlapping Protea CoCr stents were analyzed at 1-mo. All stents deployed without difficulties. Thin neointima and mild inflammation was seen in both groups at 1-wk. For 1-mo, QCA % diameter stenosis was significantly less for Protea CoCr (2±5% vs. 17±16%, p=0.032). By histomorphometry, intima thickness (0.11±0.05mm vs. 0.23±0.11mm, p=0.003) and % area stenosis (19±1% vs. 32±11%, respectively, p=0.004) were also significantly lower for Protea CoCr. The strut injury score was low and similar between the two groups. QCA % stenosis; intima thickness; and % area stenosis of overlapping Protea CoCr were 3±3%, 0.13±0.02mm, and 22±4%, respectively. Stable fibrocellular neointimal incorporation of all stents including overlapped Protea CoCr, with complete endothelialization and minimal inflammation, was seen at one month. Protea CoCr showed favorable arterial response with significant reduction of neointima formation compared to a commercial cobalt alloy BMS, one month post implant in pig coronary arteries. This ultra-thin-strut stent platform therefore appears to be a suitable and attractive alternative to current BMS. Combining the lower levels of neointima formation, fixed geometry, and uniform cell size, the Protea CoCr may be a preferred platform for next-generation drug-eluting stents.