Xience VTM Research Articles

NEW GENERATION DRUG-ELUTING STENT SUPERIOR TO BENCHMARK XIENCE DRUG-ELUTING STENT

The Resolute IntegrityTM drug eluting stent (DES; Medtronic) utilizes the Continuous Sinusoidal Technology. The PROPEL study is the first large, real world study to assess the safety, efficacy and deliverability of Resolute Integrity DES compared with a historical control, Xience VTM DES (Abbott

Twelve-month follow-up of complex patients treated with the Xience VTM everolimus drug-eluting stents in daily practice – results of the BRAVO Brazilian Registry

BackgroundThe Xience VTM everolimus-eluting stent is a new generation drug-eluting stent (DES) that incorporates a low profile cobalt-chromium platform (81μm) and a highly biocompatible polymer (fluoropolymer), which carries and controls the release of everolimus. Recent studies have demonstrated sustained safety and efficacy of the Xience VTM in the treatment of real-world populations. Our aim was to report the clinical results of 12 months of the BRAVO Brazilian protocol. MethodsThe BRAVO Registry was a prospective, non-randomized, single-arm, multicenter (25 centers) study that evaluated the late clinical results of 535 minimally selected patients treated with the drug- eluting stent Xience VTM in Brazilian daily practice. ResultsOverall, 40% of patients had diabetes, 25% prior myocardial infarction, and 42% presented with acute coronary artery syndrome. The majority of lesions (69%) was highly complex (ACC/AHA type B2 or C). The mean length and the nominal stent diameter were 19.9 ± 5.3mm and 3.0 ± 0.4mm, respectively. The angiographic and procedural successes were 99.7 and 98%, respectively. At 12 months, the cumulative rate of major adverse cardiac events, available in 100% of patients, was 5.6% (cardiac death: 1.3%; acute myocardial infarction: 3.0%; revascularization of the target lesion: 2.2%). Stent thrombosis occurred in 5 patients (0,9%), and only 1 case was reported between 6 and 12 months. ConclusionsThe drug-eluting stent Xience VTM demonstrated sustained safety and efficacy up to 12 months in the treatment of complex coronary lesions in patients from daily practice.

Seguimento de 12 meses de pacientes complexos tratados com stents farmacológicos liberadores de everolimus XIENCE V® na prática diária – resultados do registro brasileiro BRAVO

BackgroundThe Xience VTM everolimus‐eluting stents is a new generation drug‐eluting stent (DES) that incorporates a low profile cobalt‐chromium platform (81μm) and a highly biocompatible polymer (fluoropolymer), which carries and controls the release of everolimus. Recent studies have demonstrated sustained safety and efficacy of the Xience VTM in the treatment of real‐world populations. Our aim was to report the clinical results of 12 months of the BRAVO Brazilian protocol. MethodsThe BRAVO Registry was a prospective, non‐randomized, single‐arm, multicenter (25 centers) study that evaluated the late clinical results of 535 minimally selected patients treated with the drugeluting stent Xience VTM in Brazilian daily practice. ResultsOverall, 40% of patients had diabetes, 25% prior myocardial infarction, and 42% presented with acute coronary artery syndrome. The majority of lesions (69%) was highly complex (ACC/AHA type B2 or C). The mean length and the nominal stent diameter were 19.9 ± 5.3mm and 3.0 ± 0.4mm, respectively. The angiographic and procedural successes were 99.7 and 98%, respectively. At 12 months, the cumulative rate of major adverse cardiac events, available in 100% of patients, was 5.6% (cardiac death: 1.3%; acute myocardial infarction: 3.0%; revascularization of the target lesion: 2.2%). Stent thrombosis occurred in 5 patients (0,9%), and only 1 case was reported between 6 and 12 months. ConclusionsThe drug‐eluting stent Xience V™ demonstrated sustained safety and efficacy up to 12 months in the treatment of complex coronary lesions in patients from daily practice.

Resposta vascular após implante de stents liberadores de biolimus A9 com polímero bioabsorvível e stents liberadores de everolimus com polímero durável. Resultados da análise de tomografia de coerência óptica do estudo randomizado BIOACTIVE

BackgroundIn BIOACTIVE study, we evaluated vascular responses after the implant of biolimus A9‐eluting stent (BES; BioMatrixTM) and the everolimus‐eluting stent (EES; XIENCE VTM). In this study, we present the optical coherence tomography analysis (OCT) 6 months post‐intervention. MethodsPatients were randomized to treatment with BES (n = 22) or EES (n = 18). The primary outcome was the frequency of non‐covered, poorly positioned struts by OCT. ResultsOCT was performed in 26 patients (BES: n = 15; EES: n = 11) and 749 tomographic images and 7,725 stent struts were analyzed. BES and EES showed similar luminal and stent areas. Neointimal hyperplasia area, neointimal thickness and the percentage of in‐stent obstruction (8.44 ± 5.10% vs. 9.21 ± 6.36%; p = 0.74) were similar. The rates of not covered struts (BES: 2.10 ± 3.60% vs. ESS: 2.46 ± 2.15%, p = 0.77) and poorly positioned struts (BES: 0.48 ± 1.48% vs. EES 0.44 ± 1.05%, p = 0.94) were similarly low. The frequency of frames with signs consistent with peri‐strut inflammatory infiltrate was low and similar between BES (15.53 ± 20.77%) and EES (11.70 ± 27.51%; p = 0.68). ConclusionsThe second‐generation drug‐eluting stents BES and EES were equally effective at suppressing the neointimal formation after 6 months, with favorable vascular responses. The frequency of frames with peri‐strut infiltrate signals per patient was low, and lower than that observed historically with first‐generation drug‐eluting stents.

Vascular response after implantation of biolimus A9-eluting stent with bioabsorbable polymer and everolimus-eluting stents with durable polymer. Results of the optical coherence tomography analysis of the BIOACTIVE randomized trial

BackgroundIn BIOACTIVE study, we evaluated vascular responses after the implant of biolimus A9-eluting stent (BES; BioMatrixTM) and the everolimus-eluting stent (EES; XIENCE VTM). In this study, we present the optical coherence tomography analysis (OCT) 6 months post-intervention. MethodsPatients were randomized to treatment with BES (n = 22) or EES (n = 18). The primary outcome was the frequency of non-covered, poorly positioned struts by OCT. ResultsOCT was performed in 26 patients (BES: n = 15; EES: n = 11) and 749 tomographic images and 7,725 stent struts were analyzed. BES and EES showed similar luminal and stent areas. Neointimal hyperplasia area, neointimal thickness and the percentage of in-stent obstruction (8.44 ± 5.10% vs. 9.21 ± 6.36%; p = 0.74) were similar. The rates of not covered struts (BES: 2.10 ± 3.60% vs. ESS: 2.46 ± 2.15%, p = 0.77) and poorly positioned struts (BES: 0.48 ± 1.48% vs. EES 0.44 ± 1.05%, p = 0.94) were similarly low. The frequency of frames with signs consistent with peri-strut inflammatory infiltrate was low and similar between BES (15.53 ± 20.77%) and EES (11.70 ± 27.51%; p = 0.68). ConclusionsThe second-generation drug-eluting stents BES and EES were equally effective at suppressing the neointimal formation after 6 months, with favorable vascular responses. The frequency of frames with peri-strut infiltrate signals per patient was low, and lower than that observed historically with first-generation drug-eluting stents.

Real‐World Safety and Effectiveness Outcomes of a Zotarolimus‐Eluting Stent: Final 3‐Year Report of the RESOLUTE International Study

ObjectivesWe evaluated the safety and effectiveness of the Resolute™ zotarolimus-eluting stent (R-ZES) in real-world clinical practice through 3 years.BackgroundA randomized comparison of the R-ZES and the XIENCE V™ everolimus-eluting stent showed no difference in any outcomes through 3-year follow-up in high-volume academic centers. RESOLUTE International is a confirmatory trial designed to evaluate the R-ZES in real-world clinical practice.MethodsRESOLUTE International is a single arm, observational trial that enrolled 2,349 patients from 88 centers with only a few inclusion and exclusion criteria. The primary end-point was the composite of cardiac death and target vessel myocardial infarction (TV-MI) at 1 year. Secondary end-points include target lesion failure (TLF), target vessel revascularization (TVR), and their components, and stent thrombosis (ST).ResultsAt 3 years 97.2% of patients completed clinical follow-up. The mean age was 63.4 ± 11.2 years, 77.8% were male, and 30.4% had diabetes. The average number of stents per patient was 1.6 ± 1.0; and mean stent length was 30.9 ± 20.5 mm. Dual antiplatelet therapy was used in 91.1% of patients at 1 year, 43.0% at 2 years, and 34.6% at 3 years. Cardiac death and TV-MI occurred in 161 patients (7.0%). There were 6 (0.3%) very late ST events for a total ST rate of 1.1% through 3 years. The rates of clinically driven target lesion revascularization (TLR), TVR, and TLF were 5.7%, 7.4%, and 11.4%, respectively.ConclusionsThe safety and effectiveness of the R-ZES through 3 years in this real-world all-comer study was consistent with previously reported all-comer trials. (J Interven Cardiol 2013;26:515-523)

Integrity of stent polymer layer after drug-eluting stent implantation: in vivo comparison of sirolimus-, paclitaxel-, zotarolimus- and everolimus-eluting stents

Few data exist with regard to the polymer integrity of drug-eluting stents (DES) in vivo. This study aims to investigate the integrity of the polymer layer of 4 polymer-coated DES in vivo. We assessed the morphology of the polymer layer of sirolimus-eluting stent (SES; Cypher Select™), paclitaxel-eluting stent (PES; Taxus Liberté™), zotarolimus-eluting stent (ZES; Endeavour RX™) and everolimus-eluting stent (EES; Xience V™) by scanning electron microscopy after balloon expansion at nominal and high pressures in the coronary arteries of 3 pigs. Effects of kissing balloon procedure were also explored. The polymer layer of SES, PES and EES were damaged in less than 3% of the surface area with high pressure procedures, whereas the damaged area reached 38.0±2.6% in ZES (P<0.01). The polymer integrity differed greatly among DES after balloon inflation in vivo. This should be taken into account when placing DES in tortuous vessels, calcified, as well as bifurcation lesions because the polymer layer may be easily damaged in these lesions.

Clinical outcomes of different first- and second-generation drug-eluting stents in routine clinical practice: results from the prospective multicenter German DES.DE registry

Second-generation drug-eluting stents (DES) have provided better results over both bare-metal stents and first-generation DES. However, comparative data of different first- and second-generation DES in a clinical setting of all-comers have not been well studied. Baseline clinical and angiographic characteristics and in-hospital and follow-up events were recorded for enrolled patients. The composite of death, myocardial infarction, and stroke, defined as major adverse cardiac and cerebrovascular events (MACCE), as well as target vessel revascularization (TVR) was used as the primary end point. Between May 2007 and May 2009, 10,852 patients subjected to drug-eluting stent implantation were enrolled at 74 sites. 3,032 patients (27.9 %) were treated with Taxus™, 4,382 (40.4 %) with Cypher™, 1,012 (9.3 %) with Endeavor™, 1,693 (15.6 %) with Xience V™ and 733 (6.8 %) with Promus™ during this period. At 1-year follow-up, the comparison between groups revealed no significant differences with respect to overall death, MACCE, definite stent thrombosis, TVR, stroke and major bleeding. After adjustment for risk factors in final regression models, a modestly significant association of DES type to MACCE was observed (p = 0.046); however, this association could not be attributed to one particular DES. An impact of DES type on TVR was not seen after risk adjustment. Data generated from the prospective German drug-eluting stent (DES.DE) registry confirm that safety and efficacy of different first- and second-generation DES are clinically equivalent in the first year of follow-up, even in a more complex setting.

Medium to Long-Term Clinical Outcomes with Everolimus-Eluting Stents in Real-Life Percutaneous Coronary Intervention

Everolimus eluting stents (EES) have demonstrated excellent re-stenosis and thrombosis rates in a number of randomised controlled trials. This study reported the real world experience in a single tertiary centre with EES in predominantly acute coronary syndrome (ACS) patients and compared the outcomes in small and large vessels. We measured the medium to long-term major adverse cardiovascular events (MACE) defined as all-cause mortality, myocardial infarction (MI) and target vessel revascularisation (TVR) and stent thrombosis. All consecutive patients underwent percutaneous coronary intervention (PCI) with EES (PROMUSTM, Boston Scientific, Natick USA; XIENCE VTM, Abbott Vascular, Santa Clara USA) between March 2007 and September 2009 recorded in our coronary intervention registry were included in this study. All patients were advised to stay on dual antiplatelet therapy with Aspirin 100 mg/day and Clopidogrel 75 mg/day. All patients had at least 6 months of clopidogrel, government funded and a further 6 months required self funding. Four hundred and six consecutive patients received EES during the study period; 403 were included in this study and 3 were lost to follow-up. Indications for PCI were stable angina in 11% of the patients, unstable angina in 38%, non-ST elevation myocardial infarction in 43%, and ST-elevation myocardial infarction in 8%. Procedural success was achieved in 99.5% of the cases. During a median follow-up of 23 months, 3% of the patients had an MI, 3% underwent TVR, 5% all-cause mortality and 2 (0.5%) cases of definite or probable stent thrombosis. The Kaplan Meier 2-year survival and MACE free survival were 95% and 89% respectively. A subgroup analysis comparing MACE in patients who were treated with a single small (≤ 2.75 mm; n = 91) or large (≥ 3 mm; n = 118). EES did not show significant difference during the 2-year follow-up (12% vs 9%; P = 0.34). Everolimus eluting stent appears to be safe in a real world setting with satisfactory median-term outcomes which include low rates of TVR and other adverse events. EES appear to be equally effective in both small and large vessels.

In vitro and in vivo characterisation of biodegradable polymer-based drug-eluting stent

The objective of this study was to investigate the structural integrity and early vascular response of a polylactic acid-coated (i.e., biodegradable polymer) coronary drug-eluting stent (DES) (BioMatrix™; Biosensors International, Singapore) to three currently marketed FDA/CE- mark approved non-erodible polymer-coated DES in a porcine model. BioMatrix™, XIENCE V™ (Abbott Vascular, Santa Clara, CA, USA), TAXUS® Liberté™ (Boston Scientific, Natick, MA, USA), and Cypher SELECT™ (Cordis, Johnson & Johnson, Miami, FL, USA) stents were implanted in pig coronaries for seven days. Polymer integrity was assessed by scanning electron microscopy (SEM) following tissue digestion. In vitro expansion of the BioMatrix™ was also performed. SEM analysis of in vivo stents demonstrated polymer defects on the abluminal surface of all DES including polymer cracking (BioMatrix™), bridging (TAXUS Liberté™), round-small defects (Cypher SELECT™), and flaking (XIENCE V™). Histologically, the myocardium revealed no evidence of acute myocardial infarction or microscopic scarring, moreover all intramyocardial vessels were found to be patent with no evidence of emboli. In vitro results demonstrated greater BioMatrix™ polymer cracking and lifting. These results illustrate the presence of polymer defects in all DES (TAXUS Liberté™, Cypher SELECT™, XIENCE V™, BioMatrix™) implanted seven-days in pigs, with absence of myocardial damage in this small number of samples. Polymer coating irregularity was greater in BioMatrix™ stent expanded in vitro as compared to in vivo, suggesting simulated benchtop deployment induces greater damage to the biodegradable polymer coating than in vivo deployment in healthy porcine coronary arteries.

Evolution of the Coronary Artery Stent

"Necessity, who is the mother of invention." - Plato. There has been a steady rise in the incidence and prevalence of coronary artery disease. In most developed countries, it is the number one cause of morbidity and mortality. As this disease has become an ever increasing burden on society, it has spurred on the development of many radical and innovative procedures and implants. This paper will discuss, briefly, the history of coronary interventions ranging from coronary artery bypass grafts (CABG) to drug-eluting stents. It will then compare and contrast some of the several drug-eluting stents available on the market today; specifically focusing on the Cypher™, Taxus™, Endeavour™, and Xience VTM stents. The comparisons will include a basic overview of the specifications of each stent as well as the short- and long-term outcomes of these implants. Finally, the paper will provide an introduction to some of the latest stent technology awaiting FDA approval.

SPIRIT clinical trial program

Percutaneous coronary angioplasty started a revolution by providing a mechanical means of relieving angina. Abrupt vessel closure and restenosis emerged as its major limitations. Bare-metal stents dramatically reduced acute vessel closure, but restenosis, although significantly reduced, remained a clinical problem. Drug-eluting stents mitigated the problem of restenosis to a large extent. However, a small but significant increase in very-late stent thrombosis rates have been noted. Newer stents have been introduced in order to improve the efficacy and safety of stent implantation. The everolimus-eluting Xience V™ stent has been extensively evaluated in the SPIRIT clinical trial program. This article summarizes the various studies of this program and their impact on clinical practice.

Scanning electron microscopic analysis of different drug eluting stents after failed implantation: From nearly undamaged to major damaged polymers

Implantation of drug eluting stents (DES) in tortuous and/or calcified vessels is much more demanding compared with implantation of bare metal stents (BMS) due to their larger diameters. It is unknown whether drug eluting stent coatings get damaged while crossing these lesions. In 42 patients (34 male, 68.1 +/- 10 years) with 45 calcified lesions (15.9 mm +/- 7.9 mm), DES could not be implanted, even after predilatation. Diabetes was present in 19 patients (45%). Sixty-one stents were used; 19 Cypher select, 18 Taxus Liberté, 10 CoStar, 5 Endeavor RX, 4 Xience V. 3 Janus Carbostent, 1 Yukon Choice S, and 1 Axxion DES. The entire accessible surface area of these stents, in either the unexpanded and expanded state, were examined with an environmental scanning electron microscope (XL30 ESEM, Philips) to evaluate polymer or surface damage. The polymers of Taxus Liberte, Cypher Select, Xience V, CoStar, and Janus DES were only slightly damaged (less than 3% of surface area), whereas the Endeavor RX Stents showed up to 20% damaged surface area. In DES without a polymer (Yukon and Axxion), it could be shown that most of the stent surface (up to 40%) were without any layer of drug. Placement of drug eluting stents in tortuous vessels and/or calcified lesions could cause major surface damage by scratching and scraping of the polymer or drug by the arterial wall, even before implantation. There were remarkable differences among the stents examined, only minor damage with the Cypher, Taxus Costar, Janus, and Xience V, whereas the Endeavor, the Yukon, and the Janus DES showed large areas of surface injury.

TCT-376: Comparison of Two-year Outcomes of Endeavor™ and Xience V™ Stents in the Real-World

TCT-376: Comparison of Two-year Outcomes of Endeavor™ and Xience V™ Stents in the Real-World

Xience V™ everolimus-eluting coronary stent

Drug-eluting stents are widely used for the treatment of coronary artery disease to reduce the risk of restenosis found with bare-metal stents. Nevertheless, there are concerns about device deliverability and safety with the initial generation of drug-eluting stents. The second-generation Xience V™ everolimus-eluting stent incorporates advanced design features such as a cobalt–chromium stent platform coated with an antirestenotic drug, everolimus, incorporated into a biocompatible polymer with a long history of medical use. The efficacy of the stent has been demonstrated with low rates of angiographic restenosis, whilst randomized trials comparing the Xience V everolimus-eluting stent to the first-generation Taxus® paclitaxel-eluting stent have found a reduction in repeat revascularization rates. Further randomized trials, including ‘all-comer’ patients and registries of unselected patients are currently further evaluating the efficacy and safety of the Xience V stent in high-risk, complex cases.

XIENCE V™ Stent Design and Rationale

Drug‐eluting stents (DES) are a preferred treatment modality for occlusive coronary artery disease. First‐generation DES have demonstrated high levels of efficacy. However, concerns have been raised over late thrombotic events. XIENCE V™ everolimus‐eluting coronary stent is a second‐generation DES designed to be more deliverable and safe, while maintaining efficacy in a broad patient population compared with first‐generation DES. 1 − 3 As a drug/device combination product, the overall performance of a DES is determined by its components and how well they are integrated. XIENCE V utilizes the MULTI‐LINK VISION® stent, the antiproliferative drug everolimus, a fluorinated polymer drug carrier, poly(vinylidene fluoride‐co‐hexafluoropropylene) (PVDF‐HFP), and a stent‐specific delivery system. A DES coating must fulfill the multiple goals of biocompatibility, controlled drug release and maintenance of the coating durability through stent crimping, and expansion in vivo. The XIENCE V coating utilizes a two‐layer coating system composed of an acrylate primer and a fluorinated copolymer drug reservoir. Fluorinated polymers have a long history of use in permanent vascular implant applications. The XIENCE V fluorinated copolymer offers in vivo biocompatibility combined with excellent chemical stability and high purity. Described in this article are the design rationale and polymer selection criteria. The hemocompatibility and biocompatibility of the fluorinated polymer coating are discussed. Characterization results on drug release control, possible drug release mechanism, coating integrity, coating uniformity, and fatigue resistance are also presented.

XIENCE V™ Everolimus‐Eluting Coronary Stent System: A Preclinical Assessment

Background: The XIENCE V™ everolimus‐eluting coronary stent system is a second‐generation drug‐eluting stent designed for safety and efficacy in the interventional treatment of coronary artery disease and in preventing in‐stent restenosis. A comprehensive preclinical program was completed to aid in the scientific design and to demonstrate the safety of XIENCE V. Methods: Studies evaluating clinical dose selection, pharmacokinetics, single and overlapping stent safety, polymer safety, and maximum dose (8× everolimus) safety were conducted in the porcine coronary arterial model at 28, 90, 180 days, and 1 and 2 years. Additionally, a subset of studies was conducted in the rabbit iliac arterial model. Results: Morbidity and mortality rates for all preclinical studies were exceptionally low, being less than 1%. The arterial response observed in the clinical dose selection study and in all safety studies was typified by benign neointimal hyperplasia with endothelialization by 28 days. Everolimus was released in a controlled manner for 120 days and remained primarily localized within the stented arterial region, which was evidenced histologically as peristrut fibrin. The temporal presence of peristrut fibrin matched the everolimus‐elution profile. Thrombosis, malapposition, medial loss, or other adverse effects were not observed in any preclinical studies. Conclusion: XIENCE V has demonstrated safety via an extremely comprehensive preclinical program published to date for a DES system, with data generated in two species to 2 years. The preclinical data, along with the SPIRIT clinical trial data, demonstrate the excellent safety and potential efficacy profile of XIENCE V.