Endothelial Progenitor Cell Capture Stent Research Articles

Bioaffinity-based surface immobilization of antibodies to capture endothelial colony-forming cells.

Maximizing the re-endothelialization of vascular implants such as prostheses or stents has the potential to significantly improve their long-term performance. Endothelial progenitor cell capture stents with surface-immobilized antibodies show significantly improved endothelialization in the clinic. However, most current antibody-based stent surface modification strategies rely on antibody adsorption or direct conjugation via amino or carboxyl groups which leads to poor control over antibody surface concentration and/or molecular orientation, and ultimately bioavailability for cell capture. Here, we assess the utility of a bioaffinity-based surface modification strategy to immobilize antibodies targeting endothelial cell surface antigens. A cysteine-tagged truncated protein G polypeptide containing three Fc-binding domains was conjugated onto aminated polystyrene substrates via a bi-functional linking arm, followed by antibody immobilization. Different IgG antibodies were successfully immobilized on the protein G-modified surfaces. Covalent grafting of the protein G polypeptide was more effective than surface adsorption in immobilizing antibodies at high density based on fluorophore-labeled secondary antibody detection, as well as endothelial colony-forming cell capture through anti-CD144 antibodies. This work presents a potential avenue for enhancing the performance of cell capture strategies by using covalent grafting of protein G polypeptides to immobilize IgG antibodies.

Final 5-year results of the TRIAS-LR: a multi-centre, randomized trial comparing the Genous endothelial progenitor cell capturing stent with bare metal stents in patients with low risk for restenosis

Abstract Introduction The Genous stent is a bare metal stent (BMS) together with a technique of capturing endothelial progenitor cells. The successor of the Genous endothelial progenitor cell capturing (EPC) stent, the COMBO stent, combines this technique with the drug eluting polymer. The current studies showed promising results of the COMBO stent, however the additional value of EPC technique in overcoming neointimal hyperplasia has yet to be proven. Purpose This study sought to evaluate the efficacy and safety of the Genous EPC stent compared to BMS in a patient population with low risk for restenosis. Methods TRIAS-LR was an investigator-initiated, prospective, multicentre, single blind trial randomizing patients with low risk of restenosis 1:1 to Genous ECS or BMS. Patients were recruited between 2007 and 2014 at 31 sites across Europe. The study enrolment was terminated at 70% of the planned inclusion due to slow enrolment and change of guidelines. Patients or lesions were considered low risk if all of the following criteria were met: 1) reference vessel diameter >2.8mm, 2) lesion length <20mm, 3) no thrombolysis in myocardial infarction (TIMI) flow of 0, and 4) patient without diabetes mellitus. Clinical follow-up was obtained yearly. The trial was monitored and independent clinical event committee adjudicated serious adverse clinical events. The primary endpoint was target lesion failure (TLF), composite of cardiac death, target-vessel myocardial infarction (TV-MI) or target lesion revascularization (TLR) at 1 year. Secondary endpoint included the composite of death or MI at 5-year follow-up. Results In total, 838 patients were enrolled of whom 422 patients with 476 lesions were randomly assigned to Genous EPC stent and 416 patients with 480 lesions to BMS. The mean age was 64 years, 74% were males and in 76% patients were treated in elective setting. At 1 year TLF had occurred in 3.6% (n=15) of the Genous arm and in 6.1% (n=25) of the BMS arm (p=0.094; risk difference of −2.5%). However, this difference disappeared, at 5-years of follow-up; TLF rate was 12.6% (n=51) in the Genous arm versus 14.3% (n=58) in the BMS arm (p=0.385; risk difference of −1.7%). The secondary objective of the composite death or MI at 5 years occurred in 11.6% (n=47) in the Genous arm and 9.9% (n=40) in the BMS arm (p=0.479; risk difference of 1.7%). At 5 years definite stent thrombosis (ST) occurred in 0.5% (n=2) of the Genous arm, no definite ST had occurred in the BMS arm (p=0.162). Conclusion TRIAS-LR trial showed no differences between Genous EPC and BMS throughout 5-year follow-up in patients considered as low risk of restenosis. Kaplan-Meier plot of composite endpoints Funding Acknowledgement Type of funding source: Private company. Main funding source(s): OrbusNeich Medical BV

Late endothelial progenitor cell-capture stents with CD146 antibody and nanostructure reduce in-stent restenosis and thrombosis

The restoration of damaged endothelium is promising to reduce side effects, including restenosis and thrombosis, in the stent treatment for vascular diseases. Current technologies based on drug delivery for these complications still do not satisfy patients due to invariant recurrence rate. Recently, even if one approach was applied to clinical trial to develop the firstly commercialized stent employing circulating endothelial progenitor cells (EPCs) in blood vessels, it resulted in failure in clinical trial. Based on instruction of the failed case, we designed an advanced EPC-capture stent covered with anti-CD146 antibody (Ab) immobilized silicone nanofilament (SiNf) for the highly efficient and specific capture of not early but late stage of EPCs. In vitro cell capture test demonstrates enhanced capture efficiency and adhesion morphology of late EPCs on the modified substrate. The modified substrates could capture 8 times more late EPCs and even 3 times more mesenchymal stem cells (MSCs) as compared to unmodified one. A porcine model with high similarity to human reproduced in vivo results ideally translated from in vitro cell capture results. As restenosis indicators, lumen area, neointimal rate and stenosis area for modified stents were reduced at the range of 30-60% as compared to those for bare metal stent (BMS). Fibrin score indicating thrombosis was lowered less than half as comparing to that on BMS. These inspiring results are attributed to ~2-fold increased endothelial coverage, determined by immuno-histological staining. Taken together, the CD146 Ab-armed nanofilamentous stent could show great performance in the reduction of thrombosis and restenosis through re-endothelialization due to highly efficient specific cell capture. Statement of SignificanceStents have been developed from simple metal stents to functionalized stents for past decades. However, they have still risks to relapse the occlusion in stented arteries. In this paper, we describe the fabrication and optimization of cell capturing stents to maximize the effective re-endothelialization through the serial coating of silicone nanofilaments and anti-CD146 antibody. The nanofilaments increase the amount of coated antibodies and provide the anchoring points of circulating angiogenic cells for strong focal adhesion. We demonstrate high immobilizing ability of circulating angiogenic cells (endotheliali progenitor cells and mesenchymal stem cells) in vitro under similar shear stress to coronary arteries (15 dyne/cm2). Also, we show accelerating re-endothelialization and the efficient prevention of restenosis in porcine coronary arteries in vivo.

P954Value of a single bolus erythopoetin in STEMI patients treated with the Genous endothelial progenitor cell capture stent

Abstract Background The Endothelial Progenitor Cell (EPC) stent was designed to capture circulating EPCs and promote early stent re-endothelization. Erythropoietin (EPO) stimulates mobilization of EPC from the bone marrow. Combination of EPO and the EPC stent in the setting of ST-segment elevation myocardial infarction (STEMI) has never been investigated. Methods STEMI patients enrolled in the HEBE-III trial were randomized to a single bolus of EPO or No-EPO after implantation of the EPC capture stent. Late lumen loss (LLL) was determined at 9-month angiographic follow-up. Clinical data was collected at 30 days and 12 months. Results 196 patients were randomized to EPO (n=100) or No-EPO (n=96). No significant difference in baseline characteristics was observed between the two groups. A significant reduction in angiographic LLL was observed with EPO (0.43±0.57mm) as compared to No-EPO (0.74±0.63mm) (p=0.011). At 12 months follow up, no difference with regard to death or re- infarction was observed in both groups, whereas significant reduction in the need for target vessel revacularization for the EPO versus No-EPO was observed with rates of 7.1% and 19.1% respectively (p=0.013). Angiographic and clinical results EPO (n=39) No-EPO (n=45) P-value Angiography Lume late loss 0.43±0.57 0.74±0.63 0.011 12 months clinical Death 0 0 ns Re infarction 0 1 (2.2%) ns Additional PCI 4 (10.3%) 17 (37.8%) 0.004 CABG 2 (5.1%) 2 (4.4%) ns CVA 0 0 ns Bleeding 3 (7.7%) 4 (8.9%) ns ns = not significant; CVA = cerebrovascular accident; CABG = coronary bypass graft; PCI = percutaneous coronary intervention. Conclusion In STEMI patients treated with EPC capture stent, additional EPO can further improve angiographic LLL

P2798Final 5-year outcomes of the TRIAS High Risk of Restenosis; a multi-centre, randomized trial comparing endothelial progenitor cell capturing stent with drug-eluting stents

Abstract Background One of the major long-term disadvantages of percutaneous coronary intervention (PCI) remains in-stent restenosis and need for repeat revascularisation. The polymer-regulated delivery of cytotoxic or cytostatic drugs, on drug-eluting stents (DES), impede the natural healing response of the damaged vessel wall. In animals, endothelial progenitor cells (EPCs) beneficially influence the repair of the coronary vessel wall after damage by stent placement. It is hypothesized that after immobilisation the EPCs differentiate into a functional endothelial layer and that this layer will prevent neointimal proliferation and thrombus formation. Anti-CD34+ antibodies are able to capture the EPCs. The Genous stent consist of a bare-metal stent with anti-CD34+ antibody coating. Purpose Demonstrating long-term performance of Genous EPC capturing stent (ECS) relative to DES regarding target lesion failure (TLF); the composite of cardiac death, myocardial infarction (MI) and any target lesion revascularisation (TLR) within 5 years. Methods We undertook an international, clinical trial in 26 centres planning to randomise 1300 patients with stable coronary artery disease and with a high risk of restenosis between treatment with either ECS or DES. After a routine review with 50% of the patients enrolled, early cessation of the trial was recommended by the data and safety monitoring board when TLF in the ECS population was substantially higher and treatment of new patients with an ECS would be unreasonable. The trial was terminated for safety reasons. Results A total of 622 were randomly assigned to receive either Genous ECS (304 patients, 367 lesions) or DES (318 patients, 388 lesions). Five year follow-up data was obtained in 95.5% of patients. TLF occurred in 29.1% of the ECS-treated patients and in 16.0% of the DES-treated patients (p<0.001) (Figure 1). This difference was driven by higher rates of TLR (22.9% vs. 10.7%, p<0.001), but not by cardiac death (6.5% vs. 4.5%, p=0.268), or MI (5.8% vs. 3.6%, p=0.175). Definite or probable stent thrombosis was seen in 8 ECS-treated patients (2.7%) and in 3 DES-treated patients (1%), p=0.11. Figure 1. KM curves of TLF at 5year fu. Conclusion The Genous ECS is not sufficiently strong to compete with DES in terms of restenosis prevention in patients/lesions with a high risk of restenosis. If the addition of a EPCs capturing layer on a DES, like the COMBO stent, provides a lower risk of restenosis compared to DES will be tested in the ongoing SORT-OUT X trial. Acknowledgement/Funding OrbusNeich

Prevention of in-stent restenosis with endothelial progenitor cell (EPC) capture stent placement combined with regional EPC transplantation: An atherosclerotic rabbit model.

Even with drug-eluting stents, the risk of in-stent restenosis (ISR) remains high. The goal of this study was to investigate the use of an endothelial progenitor cell (EPC) capture stent plus regional EPC transplantation to reduce the ISR rate. Endothelial progenitor cell capture stents were fabricated using fibrin gel and anti-CD34 plus anti-VEGFR-2 dual antibodies. Twenty male New Zealand white rabbits established as an atherosclerotic model were randomly divided into two groups: group 1 (n = 10), in which EPC capture stents were deployed into the right iliac artery; and group 2 (n = 10), in which sirolimus-eluting stents were placed. In both groups, EPCs were transplanted into target vessels beyond the stents, with outflow blocked. Radiologic-pathologic correlation outcomes were reviewed after 2 months. The technical success rate of EPC capture stent placement plus EPC transplantation was 100%. The ISR rate in group 1 was lower than in group 2 (1/10 vs. 4/10; p > 0.05). Minimal luminal diameters were larger in group 1 than in group 2 (computed tomographic angiography, 1.85 ± 0.15 mm vs. 1.50 ± 0.20 mm; duplex ultrasound, 1.90 ± 0.10 mm vs. 1.70 ± 0.30 mm; p > 0.05). Transplanted EPCs were tracked positively only in group 1. Pathologic analysis demonstrated neointimal hyperplasia thickness of 0.21 ± 0.09 mm in group 1 vs. 0.11 ± 0.07 mm in group 2 (p < 0.05). Endothelial progenitor cell capture stent placement plus local EPC transplant decreases the ISR rate through thrombosis reduction rather than through neointimal hyperplasia inhibition.

Clinical Outcomes One Year and Beyond After Combination Sirolimus-Eluting Endothelial Progenitor Cell Capture Stenting During Primary Percutaneous Coronary Intervention in ST-Segment Elevation Myocardial Infarction.

Primary percutaneous coronary intervention (PCI) during acute ST-segment elevation myocardial infarction (STEMI) represents a thrombotic milieu and is associated with delayed healing after stenting. The pro-healing combination sirolimus eluting endothelial progenitor cell (EPC) capture stents encourage early endothelialization after stenting and may be beneficial in the STEMI population. We aim to evaluate the clinical outcomes one year and beyond for patients with STEMI who received the combination sirolimus eluting EPC capture stents during primary PCI. All STEMI patients implanted with combination sirolimus eluting EPC capture stents during primary PCI from November 2013 to December 2016 were enrolled. The primary outcome was target lesion failure (TLF) at in-hospital, one-month, one-year and beyond one year. A total of 260 consecutive STEMI patients (283 lesions) were implanted with 313 combination sirolimus eluting EPC capture stents during primary PCI. Mean age was 56.1 ± 11.2 years and 88.8% were male. One in ten patients (10.9%) had cardiogenic shock on presentation, 7.3% needed mechanical ventilation and 7.7% had intra-aortic balloon pump inserted. A total of 97.9% of lesions achieve final TIMI 3 flow. Device success was seen in all patients. At extended follow up period (median 23.4 months), the clinical outcomes were TLF 8.8%, major adverse cardiovascular events 10.8%, cardiac mortality 4.2%, target vessel myocardial infarction 3.4%, target lesion revascularization 3.8%, and definite stent thrombosis 1.9%. This study demonstrated acceptable clinical outcomes for an all-comers STEMI patients undergoing primary PCI with the use of combination sirolimus eluting EPC cell capture stents.

9-year clinical follow-up of patients with ST-segment elevation myocardial infarction with Genous or TAXUS Liberté stents

ObjectivesThis matched-cohort retrospective study investigated the long-term (9-year) safety and efficacy outcomes of patients with ST-segment elevation myocardial infarction (STEMI) and primary percutaneous coronary intervention (pPCI) with Genous (n = 102) versus TAXUS Liberté (n = 101) stents in 2006–2008.BackgroundIn the era of off-label use of drug-eluting stents for pPCI in patients with STEMI, the use of first-generation Genous stents (endothelial progenitor cell capture stents that have a passive coating and accelerate re-endothelialization) was proposed.MethodsThe primary endpoint was 9-year major adverse cardiac and cerebrovascular events (MACCE), including all-cause death, re-infarction, target vessel revascularization (TVR), and stroke. The secondary endpoints were the separate primary endpoint events at pre-defined time-points (in-hospital, 6 months, and yearly) and stent thrombosis. Time-dependent 9-year composite MACCE, all-cause death, and TVR were compared using Kaplan-Meier estimates and multivariate Cox regression models.ResultsPropensity score analysis confirmed the comparability of the groups. Patients in the Genous and TAXUS groups had 7 and 1 acute definitive stent thrombosis events, respectively (p<0.001). There was a trend towards higher in-hospital MACCE in the Genous group (10.8%) versus the TAXUS group (4.0%). Kaplan-Meier analysis showed that 9-year MACCE was significantly worse in the Genous than in the TAXUS group. The in-hospital, 6-month, 1-year, and 9-year mortality rates were 7.8%, 8.8%, 9.8%, and 23.5% in the Genous group and 2.0%, 3.0%, 4.0%, and 16.8% in the TAXUS group.ConclusionsHigher peri-procedural, in-hospital, and short-term mortality led to worse outcomes for first-generation Genous stents versus TAXUS Liberté stents for pPCI in STEMI. TAXUS Liberté stents had more favorable 9-year clinical outcomes.

Five‐year follow‐up of the endothelial progenitor cell capturing stent versus the paxlitaxel‐eluting stent in de novo coronary lesions with a high risk of coronary restenosis

To assess the long-term safety and clinical efficacy of the Genous endothelial progenitor cell capturing stent (ECS) compared with the TAXUS Liberté paclitaxel-eluting stent (PES) in lesions with a high risk of restenosis. Instead of the use of cytotoxic or cytostatic drugs in drug-eluting stents, a "pro-healing" approach in ECS may overcome impeded healing response due to delayed functional endothelialization of the stent struts. In the prospective, randomized TRIAS pilot study 193 patients with coronary artery lesions carrying a high risk of restenosis were included (ECS: n = 98, PES: n = 95). The primary focus of this analysis was target vessel failure (TVF) at 5 years. Dual antiplatelet therapy was prescribed for ≥1 month after ECS and for ≥6 months after PES. At 5 years follow-up, no significant differences were found in TVF (ECS 24% vs. PES 29%, risk difference 95% confidence interval (RDCI) -17.3% to 7.4%). Between 2 and 5 years after the index procedure, low numbers of TVF were observed in ECS compared with PES (ECS 4% vs. PES 16%, RDCI -20.8% to -2.3%). There was no definite stent thrombosis in ECS compared with four patients in the PES group. This is the first randomized study providing very long-term clinical efficacy and safety of the ECS in lesions carrying a high risk of restenosis. At 5 years follow-up, TVF rates in ECS group are numerically lower compared with PES due to an increase of events between 2 and 5 years after the index procedure.

Endothelial progenitor cell capture stents versus drug-eluting stents for angina or acute coronary syndrome

Reason for withdrawal from publication The Cochrane Heart Group withdrew this protocol as the current author team is unable to progress to the final review stage. The editors consider this title as low priority for the current portfolio of the Heart Group and therefore this title is not open to a new author team.

Can improvements in our physiological understanding yield information on the utility of endothelial progenitor cell capture stents?

intervention (PCI) patients. The index of myocardial resistance (IMR) was significantly lower in the latter than in the former group 6 to 12 months after index PCI. IMR can be used to diagnose microvascular dysfunction [4], which is known to be associated with an increased risk of adverse cardiovascular events [5]. Previous studies on the effects of DES implantation on en dothelial function have yielded mixed results. The effects of stent type on microvascular function have not been

Next-generation DES: the COMBO dual therapy stent with Genous endothelial progenitor capturing technology and an abluminal sirolimus matrix

In contrast to the use of cytotoxic or cytostatic drugs, a ‘pro-healing’ approach may have an effect that is beneficial on clinical outcomes. The endothelial progenitor cell capturing stent (ECS) technology accelerates re-endothelialization after implantation in animal models and in the human arteriovenous shunt model. Several clinical studies have shown its safety in non-complex lesions. However, in the prevention of in-stent restenosis in complex lesions, the ECS is less effective compared with drug-eluting stents. The novel COMBO dual therapy stent is the first stent to combine accelerated endothelial coverage and control of neo-intimal proliferation using a pro-healing technology with an abluminal elution of sirolimus. In the randomized REMEDEE trial, the COMBO dual therapy stent showed similar angiographic and clinical outcomes compared to the paclitaxel-eluting stent. The REMEDEE-OCT study showed equal vascular healing as assessed by optical coherence tomography of the COMBO dual therapy stent compared to the Xience-V stent.

Safety and effectiveness of the Genous™ endothelial progenitor cell-capture stent in the first year following ST-elevation acute myocardial infarction: A single center experience and review of the literature

The Genous™ stent (GS) is designed to accelerate endothelization, which is potentially useful in the pro-thrombotic environment of ST-elevation acute myocardial infarction (STEMI). We aimed to evaluate the safety and effectiveness of the GS in the first year following primary percutaneous coronary intervention (PCI) and to compare our results with the few previously published studies. All patients admitted to a single center due to STEMI that underwent primary PCI using exclusively GS, between May 2006 and January 2012, were enrolled. The primary study endpoints were major adverse cardiac events (MACEs), defined as the composite of cardiac death, acute myocardial infarction and target vessel revascularization, at one and 12 months. In the cohort of 109 patients (73.4% male, 59 ± 12 years), 24.8% were diabetic. PCI was performed in 116 lesions with angiographic success in 99.1%, using 148 GS with median diameter of 3.00 mm (2.50-4.00) and median length of 15 mm (9-33). Cumulative MACEs were 2.8% at one month and 6.4% at 12 months. Three stent thromboses (2.8%), all subacute, and one stent restenosis (0.9%) occurred. These accounted for the four target vessel revascularizations (3.7%). At 12 months, 33.9% of patients were not on dual antiplatelet therapy. GS was safe and effective in the first year following primary PCI in STEMI, with an apparently safer profile comparing with the previously published data. We report the safety and effectiveness of the Genous™ stent (GS) in the first year following primary percutaneous coronary intervention in ST-elevation acute myocardial infarction. A comprehensive review of the few studies that have been published on this subject was included and some suggest a less safe profile of the GS. Our results and the critical review included may add information and reinforce the safety and effectiveness of the GS in ST-elevation in acute myocardial infarction.

Six types of drug-eluting stents show the similar clinical outcomes for the treatment of ST-segment elevation myocardial infarction

Purpose: There were no published data regarding the clinical efficacy and safety of endothelial progenitor cell capture-stents (EPC-S) compared with 1st generation (sirolimus-eluting stent, SES and paclitaxel-eluting stent, PES) and 2nd generation (zotarolimus-eluting stent, ZES and everolimus-eluting stent, EES and zotarolimus-eluting stent with biolinx polymer, ZES-BP) drug-eluting stents (DES) following primary percutaneous coronary intervention (PCI) in ST-elevation myocardial infarction (STEMI). We evaluated the one-year outcome of EPC capture-stents vs 5 types DES (ZES-BP, EES, ZES, SES and PES) for the primary PCI. Methods: A prospective, open-labeled, multi-center cohort was performed. The primary endpoint was major adverse cardiac event (MACE): the composite of cardiac death (CD), recurrent MI and ischemia-driven target vessel revascularization (TVR). Stent thrombosis (ST) was defined by ARC. Results: Total 1055 patients (EPC-S=80, ZES-BP=178, EES=197, ZES=203, SES=203, PES=194) who were completed more than 1 year were analyzed. 1 year MACE were 6.3%, 3.4%, 2.0%, 5.9%, 3.4% and 5.7% in EPC-S, ZES-BP, EES, ZES, SES and PES group (p=ns). Cardiac death were 5.0%, 1.0%, 2.5%, 1.5% and 1.0%, respectively (p=ns). ST were 0%, 0%, 2.0%, 2.0% and 2.0% (p=ns). View this table: Clinical outcomes at 12 months Conclusions: Campared with 1st and 2nd generation DES (SES, PES, ZES, EES and ZES-BP), EPC-S showed similar one-year clinical outcomes in terms of MACE in patients with STEMI following primary PCI.

Primary PCI with endothelial progenitor cell-capture stent in patient with skull base fracture and aspirin allergy

Primary PCI with endothelial progenitor cell-capture stent in patient with skull base fracture and aspirin allergy

A Meta‐Analysis of the Impact of EPC Capture Stent on the Clinical Outcomes in Patients with Coronary Artery Disease

Damage to the vascular endothelium may be one of the pathophysiological causes of in-stent thrombosis and restenosis. Endothelial progenitor cell (EPC) capture stents (ECS) have the ability to accelerate the damage repair process. However, the clinical outcomes of ECS remain unknown thus far. To evaluate the impact of ECS use on the clinical outcomes of patients with coronary artery disease by comparing ECS to drug-eluting stent (DES) and/or bare metal stent (BMS). Studies and abstracts were retrieved from the PubMed, Cochrane Library, and EMBASE online databases and from the conference compilations of the American Heart Association (AHA), the American College of Cardiology (ACC), and Transcatheter Cardiovascular Therapeutics (TCT). These studies were analyzed to investigate whether there was a difference in the clinical therapeutic effects between the ECS group and the DES/BMS group. The primary clinical end-point events were in-stent thrombosis and target lesion revascularization (TLR). The secondary clinical end-point events were target lesion failure (TLF), total mortality, cardiac death, and myocardial infarction (MI). A total of 2,024 patients were enrolled in the analysis of in-stent thrombosis. There was no significant difference in the incidence of in-stent thrombosis between the ECS group and the DES/BMS group. A total of 1,745 patients were enrolled in the analysis of TLR, and there was no significant difference in the TLR incidence between the ECS group and the DES/BMS group. However, compared with DES, the TLR incidence for ECS increased 1.73-fold (relative risk [RR]: 1.73, 95% confidence interval [95% CI]: 1.01-2.94, P = 0.04). Moreover, the incidence of cardiac death and TLF also increased 3.54-fold (RR: 3.54, 95% CI: 1.13-11.08, P = 0.03) and 1.90-fold (RR: 1.90, 95% CI: 1.05-3.45, P = 0.03), respectively. But compared with BMS, there is no significance of the clinical events. Compared with DES/BMS use, ECS use may not reduce the incidence of in-stent thrombosis and TLR. In addition, the incidence of TLR and cardiac death with ECS is possibly relatively higher compared with DES and no difference compared with BMS, but this also needs more large RCTs to guarantee.

Comparison between endothelial progenitor cell capture and bare metal stents in coronary artery disease patients at high risk for instent restenosis and thrombosis

Backgroud Since EPCs represent a pool of cells which contribute to the endothelial repair after vascular injury, the increased homing and retention of these cells at the site of stent implantation may increase and speed up the process of endothelialization. The new bioengineered stent with the immobilized antibody against CD34 antigen bound to the surface of the struts is thought to enable the stent to capture circulating EPCs from the blood stream to establish a functional endothelial lining preventing platelet adhesion and activation, and thus thrombus formation, with modulation of the foreign body inflammatory response through acceleration of the natural healing process, thus preventing ISR. This may minimize the need for long term dual anti-platelet therapy. Objectives The purpose of this study was to compare the efficacy of the new endothelial progenitor cell (EPC) capture stents with that of bare metal stents in coronary artery disease patients at high risk for instent restenosis and thrombosis. Methods We randomly assigned 38 patients with lesions carrying a high risk of restenosis to have the Genous stent or a bare metal stent implanted. Lesions were considered high risk of restenosis if one of the following applied: a chronic coronary artery occlusion; a coronary artery stenosis with a length of more than 20 mm; a lesion in a coronary artery with a diameter of less than 2.8 mm by QCA; or any lesion in a diabetic patient or renal failure. Results At 6 months, the rate of the primary end point, composite of ISR and IST, was 26% in the Genous stent group when compared with 58% in the bare metal stent group [ p = 0.049]. Also, no stent thrombosis was observed in the Genous stent group compared to 1 probable stent thromboses in the bare metal stent group ( p = 0.3). The cumulative rate of MACE (cardiac death, MI and clinically driven TLR) at 6 months was 26% in the Genous stent group (all due to clinically driven TLR) when compared with 52% in the bare metal stent group, a difference due to clinically driven target lesion revascularization ( p -value = 0.1). Conclusions In patients with lesions carrying a high risk of restenosis, the Genous stent resulted in a non-significant trend towards lower rate of ISR and MACE compared with bare metal stents mainly due to more repeat revascularizations in the bare metal stent group.

Endothelial Progenitor Cell Capture Stent: Safety and Effectiveness

The endothelial progenitor cell (EPC) capture stent is an innovative device that makes use of the ability of bone marrow-derived EPCs to migrate to injured arterial segments to facilitate healing. The EPC antibody surface, consisting of a covalently coupled polysaccharide intermediate coating with anti-human CD34 antibodies, is attached to a stainless steel stent. Upon stent placement, the anti-human CD34 antibodies will attract circulating EPCs, which are expected to develop into mature functional endothelium. This accelerated healing strategy aims to lower the risk of restenosis and stent thrombosis, as well as obviate prolonged dual antiplatelet therapy. Since the first-in-man study in 2003, a number of small-to-medium size registry and postmarketing studies that confirmed the good safety profile of the EPC capture stent have been published. However, due to lack of large-scale randomized trials, its effectiveness, compared with bare metal stents and drug-eluting stents, cannot be ascertained. Based on restudy angiographic data, instent late loss was approximately 0.7-0.9 mm, which compares unfavorably with that of drug-eluting stents. In order to improve the effectiveness of the EPC capture stent in reducing restenosis--while maintaining its pro-healing property--a bioengineered sirolimus-eluting stent known as the Combo stent was recently designed to combine the EPC capture technology with the abluminal elution of sirolimus. Data from animal studies have been encouraging. The first-in-man study of the Combo stent has been completed and results were presented.

Twelve-month clinical outcomes after coronary stenting with the Genous Bio-engineered R Stent in patients with a bifurcation lesion

The e-Healthy Endothelial Accelerated Lining Inhibits Neointimal Growth (e-HEALING) registry was designed to capture clinical data on the use of the endothelial progenitor cell capture stent (ECS) in routine clinical practice. In this analysis, we investigated the 12-month clinical outcomes in patients treated with an ECS for a bifurcation lesion. The worldwide, prospective, nonrandomized e-HEALING registry aimed to enroll 5000 patients treated for coronary artery disease with one or more ECS between October 2005 and October 2007. Clinical follow-up was obtained at 1, 6, and 12 months. The primary endpoint was target vessel failure (TVF), defined as the composite of cardiac death, myocardial infarction, and target vessel revascularization at 12 months. A total of 573 patients were treated for at least one bifurcation lesion and were assessed in the current analysis. Baseline characteristics showed a median age of 65 years; 21% were diabetic patients and 36% had unstable angina. A total of 63% of the bifurcation lesions were located in the left artery descending and the mean stent length was 20.7±12.6 mm. At 12 months, TVF was 12.7% and target lesion revascularization was 7.5%. Definite or probable stent thrombosis occurred in 1.7% of the patients. Moreover, one or more stents per lesion [hazard ratio (HR): 2.79, 95% confidence interval (CI): 1.60-4.86, P<0.001], predilatation (HR: 0.39, 95% CI: 0.17-0.87, P=0.023), and lesions located in the right coronary artery (HR: 4.56, 95% CI: 1.07-19.5, P=0.041) were independent predictors of TVF. In the e-HEALING registry, coronary bifurcation stenting with the ECS results in favorable clinical outcomes and low incidences of repeat revascularization and stent thrombosis.

Very late stent thrombosis due to DES fracture: Description of a case and review of potential causes

Stent fracture and subsequent stent thrombosis are known complications after stent implantation, especially in stents with closed cell design like the first generation sirolimus drug eluting stents (DES). Late stent thrombosis is very rarely encountered in our patient population, majority Chinese. We report a case of non-ST elevation myocardial infarction as a result of very late stent thrombosis (three years after implantation) due to stent fracture at the site of overlap of two first generation sirolimus DES. There were initial difficulties in restoring coronary flow by conventional reperfusion therapies but a successful outcome after implantation of an endothelial progenitor cell capture stent, with no further recurrence of ischemic event after 12 months. An attempt was made to analyze all existing factors present and contributing to the stent fracture and stent thrombosis in this case, as reported in the literature.