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Background A polymer-free biolimus-eluting stent (PF-BES) and a zotarolimus-eluting stent (ZES) recently showed similar clinical profiles and appear to be competing options in specific clinical settings of patients undergoing percutaneous coronary intervention (PCI). Whether they perform similarly also in complex procedural settings as coronary bifurcation lesions remains unaddressed. Methods All consecutive patients undergoing coronary bifurcation PCI with PF-BES or the new iteration of the ZES from three large multicenter real-world registries were included. The primary outcome was major adverse cardiovascular events (MACE), a composite of all-cause death, myocardial infarction (MI), target lesion revascularization (TLR) and stent thrombosis (ST). Multiple analyses to adjust for baseline differences were carried out including propensity-score matching, propensity-score stratification and inverse-probability-weighting. Outcomes are reported according to Cox proportional hazard models censored at 400-day follow-up. Results 1169 patients treated with PF-BES (n = 440) or ZES (n = 729) on the main branch of a coronary bifurcation lesion were included (mean age 69 ± 11 years, 75.4% male, 53.8% acute coronary syndrome at presentation, 26.6% left main bifurcation, median dual antiplatelet therapy duration 12 [range 12–12] months). MACE, all-cause death, TLR and ST tended towards non-statistically higher rates with the PF-BES as compared to the ZES. Higher MI and target vessel revascularization occurrence was observed with PF-BES. Conclusions In this large contemporary cohort of patients undergoing coronary bifurcation PCI, the occurrence of MACE was non-statistically different with the use of PF-BES and ZES devices. However, differences favoring the ZES device that may entail clinical relevance were observed. Further studies are needed to confirm these findings and explore whether they remain valid when a short dual antiplatelet therapy is adopted.

Background Very long-term outcomes according to diabetic status of patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI) with new-generation drug-eluting stents (DES) are scant. Both, the durable polymer zotarolimus-eluting stent (DP-ZES), the first DES to gain FDA-approval for specific use in patients with diabetes mellitus, and the polymer-free sirolimus- and probucol-eluting stent (PF-SES), with a unique design that enables effective drug release without the need of a polymer offer the potential to enhance clinical long-term outcomes especially in patients with diabetes mellitus. Methods We investigate 10-year clinical outcomes of the prespecified subgroups of patients with and without diabetes mellitus, randomly assigned to treatment with PF-SES versus DP-ZES in the ISAR-TEST 5 trial. The primary endpoint of interest was major adverse cardiac events (MACE), defined as the composite of all-cause death, any myocardial infarction or any revascularization. Further endpoints of interest were cardiac death, myocardial infarction related to the target vessel and target lesion revascularization as well as the individual components of the primary composite endpoint and the incidence of definite or probable stent thrombosis at 10 years. Results This analysis includes a total of 3002 patients randomly assigned to PF-SES (n = 2002) or DP-ZES (n = 1000). Prevalence of diabetes mellitus was high and comparable, 575 Patients (28.7%) in PF-SES group and 295 patients (29.5%) in DP-ZES group (P = 0.66). At 10 years 53.5% of patients with diabetes mellitus and 68.5% of patients without diabetes mellitus were alive. Regarding major adverse cardiac events, PF-SES as compared to DP-ZES showed comparable event rates in patients with diabetes mellitus (74.8% vs. 79.6%; hazard ratio 0.86; 95% CI 0.73–1.02; P = 0.08) and in patients without diabetes (PF-SES 62.5% vs. DP-ZES 62.2%; hazard ratio 0.99; 95% CI 0.88–1.11; P = 0.88). Conclusion At 10 years, both new-generation DES show comparable clinical outcome irrespective of diabetic status or polymer strategy. Event rates after PCI in patients with diabetes mellitus are considerable higher than in patients without diabetes mellitus and continue to accrue over time. Trial registration ClinicalTrials.gov, NCT00598533, Registered 10 January 2008, https://clinicaltrials.gov/ct2/show/NCT00598533?term=NCT00598533 Graphic abstract Kaplan-Meier estimates of endpoints of interest for patients with vs. without diabetes mellitus treated with PF-SES vs. DP-ZES. Bar graphs: Kaplan-Meier estimates as percentages. PF-SES: polymer-free sirolimus-eluting stent; DP-ZES: durable polymer zotarolimus-eluting stent; DM: diabetes mellitus. Comparison of event rates of individual endpoints in patients with and without diabetes mellitus treated with PF-SES vs. DP-ZES all without statistically significant differences. Comparison of event rates of individual endpoints in overall patients with vs. without diabetes mellitus significantly different (P ≤ 0.01 for all comparisons).

Objectives The aim of this study was to assess 2-year safety and efficacy of the current-generation thin composite-wire-strut durable-polymer Resolute Onyx zotarolimus-eluting stent (ZES), compared with the ultrathin-strut biodegradable-polymer Orsiro sirolimus-eluting stent (SES) in all-comers and a pre-specified small-vessel subgroup analysis. Background The Resolute Onyx ZES is widely used in clinical practice, but no follow-up data beyond 1 year have been published. The randomized BIONYX (Bioresorbable Polymer-Coated Orsiro Versus Durable Polymer-Coated Resolute Onyx Stents) trial (NCT02508714) established the noninferiority of ZES versus SES regarding target vessel failure (TVF) rates. Methods A total of 2,488 all-comer patients were treated at 7 coronary intervention centers in Belgium, Israel, and the Netherlands. The main endpoint, TVF, was a composite of safety (cardiac death or target vessel–related myocardial infarction) and efficacy (clinically indicated target vessel revascularization). Two-year follow-up data were analyzed using Kaplan-Meier methods. Results Two-year follow-up data were available for 2,460 of 2,488 patients (98.9%). TVF occurred in 93 of 1,243 patients (7.6%) assigned to ZES versus 87 of 1,245 patients (7.1%) assigned to SES (log-rank p = 0.66). There was no significant between-stent difference in individual components of this endpoint. The incidence of definite-or-probable stent thrombosis was low for both treatment arms (0.4% vs. 1.1%; log-rank p = 0.057). In patients stented in small vessels, there was no between-stent difference (TVF 8.2% vs. 8.7% [log-rank p = 0.75], target lesion revascularization 4.0% vs. 4.4% [log-rank p = 0.77]). Conclusions At 2-year follow-up, the novel thin composite-wire-strut durable-polymer Resolute Onyx ZES showed in all-comers similar safety and efficacy compared with the ultrathin cobalt-chromium-strut biodegradable-polymer Orsiro SES. The analysis of patients who were treated in small vessels also suggested no advantage for either stent.

Introduction: The increasing complexity of patients undergoing percutaneous coronary intervention (PCI) regarding both coronary anatomy and comorbidities requires dedicated devices. The Resolute Onyx (R-Onyx, Medtronic, CA, USA) stent is a novel durable polymer zotarolimus-eluting stent (ZES) promising better deliverability, increased radiopacity and lower thrombogenicity.Areas covered: In this review, we discuss device features, preclinical evidence, and clinical studies including patients treated with R-Onyx. The BIONYX and Onyx ONE studies were two major landmark trials demonstrating non-inferiority of R-Onyx as compared to other latest generation devices. We also elaborate on alternative innovations in drug-eluting stent (DES) technology and how R-Onyx fits into this field.Expert opinion: R-Onyx is designed to address the challenges of contemporary PCI, but evidence on its clinical performance is largely derived from studies on older generation devices from the ZES family. Nonetheless, all clinical studies on R-Onyx consistently show excellent outcomes, with particularly low rates of stent thrombosis, making it a promising candidate for short dual antiplatelet regimens. In addition, R-Onyx is available with a wide range of stent diameters allowing accurate sizing for both very small and very large coronary vessels.

Diabetes mellitus (DM) plays an important role in restenosis and late in-stent thrombosis (ST). The current study using optical coherence tomography (OCT) aims to compare target lesion neointima in patients with or without diabetes after zotarolimus-eluting stent (ZES) treatment. OCT images of 90,212 struts and quantitative coronary angiography (QCA) in 62 patients (32 with DM and 30 without DM) with 69 de novo coronary lesions (34 DM and 35 non-DM) both after ZES implantation and 12 ± 1 month angiographic follow-up were recorded. Patient characteristics, lesion characteristics, clinical outcomes, and OCT findings including neointimal thickness, coverage, malapposition, and intimal morphology were analyzed. Baseline patient characteristics and lesion characteristics data were similar between the two groups. Higher neointimal thickness (0.14 ± 0.09 mm vs. 0.09 ± 0.04 mm, p = 0.021), more neovascularization (3.03 ± 6.24 vs. 0.52 ± 1.87, p = 0.017) and higher incidence of layered signal pattern (12.19 ± 19.91% vs. 4.28 ± 9.02%, p = 0.049) were observed in diabetic lesions comparing with non-diabetic lesions. No differences were found in malapposition, uncovered percentage, and thrombus between the two groups (all p > 0.05). Occurrence of clinical adverse events was also similar during the follow-up period (p > 0.05). Although more neointimal proliferation and more neovascularization were found in diabetic coronary lesions when compared with non-diabetic lesions, treatment with ZES showed similar stent malapposition rate at 1-year follow-up. The data indicated that ZES treatment could possibly be effective in treating diabetic coronary lesions. ClinicalTrials.gov identifier, NCT01747356.

We compared 10-year clinical outcomes in diabetes and nondiabetes patients treated with Endeavor zotarolimus-eluting (ZES) or Cypher sirolimus-eluting coronary stents (SES). A total of 1,162 patients were randomized to ZES (169 with diabetes) and 1,170 patients were randomized to SES (168 with diabetes). Patients were further stratified by diabetes status at the time of inclusion. A subgroup of patients with diabetes (n = 88) underwent angiographic re-evaluation 10 months after stent implantation. End points included a combined end point of death or myocardial infarction, and the individual end points of death, myocardial infarction, and revascularization. In patients with diabetes, we found no difference in the combined end point (odds ratio [OR] 0.81, 95% confidence interval [CI] 0.53 to 1.24), death (OR 0.80, 95% CI 0.51 to 1.25), or in MI (OR 1.07, 95% CI 0.60 to 1.91). However, diabetics with ZES more frequently underwent coronary revascularization compared with SES patients (OR 1.93, 95% CI 1.05 to 3.66). In patients without diabetes, ZES and SES had similar 10-year rates of all end points (death: OR 1.13, 95% CI 0.93 to 1.39; MI: OR 0.80, 95% CI 0.61 to 1.05; revascularization: OR 0.81, 95% CI 0.61 to 1.09). Landmark analysis from 5 to 10 years showed no difference in outcomes between SES and ZES in either subgroup. In conclusion, at 10 years, SES and ZES performed similarly in patients with and without diabetes. Although coronary revascularization was more prevalent in diabetes patients with ZES, this may, in part, have been related to the angiographic follow-up that was offered to a subgroup of diabetes patients.

Objectives This study sought to determine clinical outcomes between treatment groups over long-term follow-up. Background The safety and efficacy of a ridaforolimus-eluting stent (RES) was evaluated in the BIONICS (BioNIR Ridaforolimus-Eluting Coronary Stent System in Coronary Stenosis) and NIREUS (BioNIR Ridaforolimus Eluting Coronary Stent System [BioNIR] European Angiography Study) trials, demonstrating noninferiority of RES in comparison with a zotarolimus-eluting stent (ZES) regarding 1-year target lesion failure (TLF) and 6-month angiographic late lumen loss, respectively. Methods Patient-level data from the BIONICS (N = 1,919) and NIREUS (N = 302) randomized trials were pooled, and outcomes in patients implanted with RES and ZES compared. Broad inclusion criteria allowed enrollment of patients with acute coronary syndromes and complex lesions. The primary endpoint was the 2-year rate of TLF or clinically driven target lesion revascularization. Results A total of 2,221 patients (age 63.2 ± 10.3 years; 79.7% men) undergoing percutaneous coronary intervention with RES (n = 1,159) or ZES (n = 1,062) were included. Clinical and angiographic characteristics were similar between groups. At 2 years, the primary endpoint of TLF was similar among patients implanted with RES and ZES (7.0% vs. 7.2%; p = 0.94). Rates of target lesion revascularization (4.8% RES vs. 4.1% ZES; p = 0.41) and target vessel–related myocardial infarction (3.1% RES vs. 3.8% ZES; p = 0.52) did not differ between groups. The overall rate of stent thrombosis was also similar (0.5% RES vs. 0.9% ZES; p = 0.39). Conclusions In a pooled analysis of 2 randomized trials, 2-year clinical outcomes were similar between patients undergoing percutaneous coronary intervention with RES and ZES. These results support the long-term safety and efficacy of RES for the treatment of a broad population of patients with coronary artery disease.

Aim Patients with diabetes mellitus are at high risk of adverse events after percutaneous revascularization, with no differences in outcomes between most contemporary drug-eluting stents. The Cre8 EVO stent releases a formulation of sirolimus with an amphiphilic carrier from laser-dug wells, and has shown clinical benefits in diabetes. We aimed to compare Cre8 EVO stents to Resolute Onyx stents (a contemporary polymer-based zotarolimus-eluting stent) in patients with diabetes. Methods and results We did an investigator-initiated, randomized, controlled, assessor-blinded trial at 23 sites in Spain. Eligible patients had diabetes and required percutaneous coronary intervention. A total of 1175 patients were randomly assigned (1:1) to receive Cre8 EVO or Resolute Onyx stents. The primary endpoint was target-lesion failure, defined as a composite of cardiac death, target-vessel myocardial infarction, and clinically indicated target-lesion revascularization at 1-year follow-up. The trial had a non-inferiority design with a 4% margin for the primary endpoint. A superiority analysis was planned if non-inferiority was confirmed. There were 106 primary events, 42 (7.2%) in the Cre8 EVO group and 64 (10.9%) in the Resolute Onyx group [hazard ratio (HR): 0.65, 95% confidence interval (CI): 0.44–0.96; P non-inferiority < 0.001; P superiority = 0.030]. Among the secondary endpoints, Cre8 EVO stents had significantly lower rate than Resolute Onyx stents of target-vessel failure (7.5% vs. 11.1%, HR: 0.67, 95% CI: 0.46–0.99; P = 0.042). Probable or definite stent thrombosis and all-cause death were not significantly different between groups. Conclusion In patients with diabetes, Cre8 EVO stents were non-inferior to Resolute Onyx stents with regard to target-lesion failure composite outcome. An exploratory analysis for superiority at 1 year suggests that the Cre8 EVO stents might be superior to Resolute Onyx stents with regard to the same outcome. Clinical trial registration ClinicalTrials.gov: NCT03321032.

Background: There are few studies which compare the efficacy and safety of the Resolute Onyx zotarolimus-eluting stent (O-ZES) and everolimus-eluting stent (EES) in patients with acute myocardial infarction (AMI). Therefore, the present study aimed to compare clinical outcomes of O-ZES and EES in patients with AMI undergoing successful percutaneous coronary intervention (PCI). Methods: From January 2016 to December 2016, the Korea Acute Myocardial Infarction Registry (KAMIR) enrolled 3,364 consecutive patients. Among them, O-ZES was used in 402 patients and EES was used in 1,084 patients. The primary endpoint was target lesion failure (TLF), as defined by composite of cardiac death, target vessel myocardial infarction (TV-MI), and ischemic driven-target lesion revascularization (ID-TLR) at 6 month clinical follow-up. Results: At 6 months, the incidence of TLF was not significantly different between O-ZES and EES group (4.0% vs. 3.9%, adjusted hazard ratio [HR] 1.17, 95% confidential interval [CI] 0.58–2.35, p = 0.665). O-ZES also showed similar results of cardiac death (3.7% vs. 3.4%, adjusted HR 1.25, 95% CI 0.59–2.63, p = 0.560), TV-MI (0.2% vs. 0.6%, adjusted HR 0.56, 95% CI 0.07–4.85, p = 0.600), ID-TLR (0.0% vs. 0.3%, p = 0.524), and definite or probable stent thrombosis (0.2% vs. 0.3%, adjusted HR 0.63, 95% CI 0.06–6.41, p = 0.696) when compared with EES. Conclusions: The present study shows that implantation of O-ZES or EES provided similar clinical outcomes with similar risk at 6-month of TLF and definite/probable ST in patients with AMI undergoing successful PCI.

Prior research has revealed poorer clinical outcomes after drug-eluting stent (DES) implantation for hemodialysis patients. This study aims to investigate the long-term clinical and angiographic outcomes after new-generation DES implantation for hemodialysis patients.We retrospectively enrolled 91 consecutive patients (118 lesions) who underwent successful new-generation DES (everolimus-, zotarolimus-, and biolimus-eluting stents) implantation for the first time. We measured the serum calcium and phosphorus levels in the blood samples obtained just before hemodialysis. The follow-up period of clinical events was, at least, 1.5 years. In this study, major adverse cardiac and cerebrovascular events (MACCE) and clinically driven target lesion revascularization were reported in 36 (39.6%) and 11 (12.1%) patients, respectively. The prevalence of peripheral artery disease was significantly higher in the MACCE group (41.7% versus 14.5%, P = 0.006). The serum calcium level was significantly higher in the MACCE group (9.34 ± 0.92 mg/dL versus 8.77 ± 0.88 mg/dL; P = 0.004). The multivariate Cox proportional hazards model revealed that the serum calcium level (hazard ratio, 1.86; 95% confidence interval [CI]: 1.26-2.77; P = 0.002), suboptimal (over 55 mg2/dL2) calcium-phosphorus product (hazard ratio, 3.27; 95% CI: 1.41-7.61; P = 0.006) and the coexistence of peripheral artery disease (hazard ratio, 3.15; 95% CI: 1.49-6.65; P = 0.003) were independent predictors of MACCE.For hemodialysis patients, MACCE remains a frequent occurrence after new-generation DES implantation and is associated with calcium-phosphate metabolism and peripheral artery disease.

Several new coronary stents have been, or soon will be, introduced in the United States. These stents incorporate certain characteristics, such as polymer-free drug coatings, ultrathin stent struts, bioresorbable polymers, and composite materials, that address currently unmet clinical needs to enhance acute stent performance, improve longer-term clinical outcomes, and obviate obligatory prolonged dual antiplatelet therapy. This article reviews the key and novel features of these stents.

Drug elution profiles must be studied in vitro to optimize a polymer-drug formulation during development of drug-eluting stents (DESs). Results from HPLC assays of drug contents and elution kinetics from a biodegradable sirolimus coating and a stable zotarolimus coating on coronary DESs are presented. Drug contents were assessed for crimped stents on the delivery system and expanded stents. The drug coating morphology and elution kinetics were demonstrated to be associated. Significant coating morphological defects were shown to cause deviations in the drug elution profile.

Background The impact of coronary artery disease (CAD) extension/complexity on outcomes and on the comparative benefits/risks of zotarolimus-eluting stent (ZES) versus bare-metal stents (BMS) remains unclear in patients at high risk of bleeding or thrombosis or at low restenosis risk. Methods We performed a post-hoc analysis of the ZEUS trial. The impact of coronary anatomic complexity measured by the SYNTAX score on the differences in outcomes following ZES and BMS was assessed at 1 year. Results The mean SYNTAX score was 16.3 ± 13.1 with a median of 12 (IQR: 7 to 22). We stratified patients according to SYNTAX tertiles (0–8: n = 563; >8–19 n = 532; >19: n = 511), and observed that the higher the score, the correspondingly higher was the rate of the primary endpoint of major adverse cardiovascular events (MACE) and other ischemic events, but not bleeding after adjustment. The superior efficacy of ZES versus BMS for MACE was consistent across SYNTAX tertiles (tertile 1: HR 0.71, 95% CI 0.44–1.13; tertile 2: HR 0.71, 95% CI 0.46–1.09; tertile 3: HR 0.83, 95% CI 0.61–1.10) without significant heterogeneity (p for trend = 0.55). This between-groups difference mainly reflected a reduction in MI and TVR without effect on mortality. There was no significant interaction between the SYNTAX score and allocated stent type with respect to ischemic and bleeding endpoints. Conclusions The SYNTAX score was predictor of major adverse cardiovascular events but not bleeding and ZES provided superior efficacy and safety than BMS across the whole spectrum of CAD complexity. SYNTAX score may be routinely used for the assessment of the ischemic risk (but not bleeding) after PCI and should not guide the decision-making for DES versus BMS in patients undergoing PCI.

Изучение профиля выделения лекарственного средства in vitro — необходимый этап при оптимизации полимерно-лекарственной композиции в процессе разработки стентов, выделяющих лекарственное вещество (ЛВ). В статье представлены результаты ВЭЖХ-анализа содержания ЛВ и кинетики его выделения из различных типов полимерно-лекарственного покрытия выделяющих ЛВ коронарных стентов (drug eluting stent — DES): биодеградируемого покрытия с сиролимусом и стабильного покрытия с зотаролимусом. Содержание ЛВ оценивали для кримпированных стентов на системе доставки, а также после раскрытия. Продемонстрирована связь морфологии лекарственного покрытия с кинетикой выделения ЛВ и показано, что крупные морфологические дефекты покрытия приводят к отклонению параметров выделения ЛВ.

Outcomes for stent-based coronary intervention of lesions with long diseased segments remain relatively unfavorable. This study sought to compare the efficacy of Resolute zotarolimus-eluting stents (R-ZES) and Xience everolimus-eluting stents (EES) for very long coronary lesions.This randomized, multicenter, prospective trial compared the use of R-ZES with EES for very long (≥50 mm) native coronary lesions. The primary end point was in-segment late luminal loss at 12-month angiographic follow-up. A total of 400 patients were needed to assess the primary end point. However, owing to very slow enrollment of patients, this trial was early terminated (302 patients were enrolled), and thus, this report provides descriptive information on primary and secondary end points. The R-ZES and EES groups had similar baseline characteristics. Lesion length was 49.6±10.2 and 50.6±13.3 mm in the R-ZES and EES groups, respectively (P=0.47). The number of stents used at the target lesion was 2.1±0.3 and 2.2±0.5, respectively. Twelve-month angiographic follow-up was performed in 50% of eligible patients. In-segment late luminal loss did not significantly differ between the R-ZES and EES groups (0.17±0.57 vs. 0.09±0.43 mm, P=0.32). In-segment binary restenosis rates were 8.1 and 5.3% in the R-ZES and EES groups, respectively (P=0.49). There were no significant between-group differences in the rate of adverse events (death, myocardial infarction, stent thrombosis, target lesion revascularization, and composite outcomes).For patients with very long native coronary artery disease, R-ZES and EES implantation showed comparable angiographic and clinical outcomes through 1 year of follow-up.

The clinical efficacy and safety of second-generation drug-eluting stents in complex percutaneous coronary interventions (PCIs) are not well established.The clinical influence of the lesion complexity after PCI with zotarolimus-eluting stents (ZES) was evaluated.From a prospective multicenter observational study, a total of 926 patients that underwent successful PCIs with ZES were included. Complex PCIs were defined as patients with ≥3 lesions treated, 3 vessels treated, severe calcified lesions, bifurcated lesions with 2 stents implanted, left main disease, chronic total occlusion lesions, and/or diffuse long (total stent length ≥60 mm) lesions and were compared to the noncomplex group. The primary outcome was incidence of target lesion failures at 2 years, defined as a composite of cardiac death, target lesion-myocardial infarctions, and target lesion revascularization.The patients were divided into complex PCI (n = 249) and noncomplex (n = 677) groups. In the complex PCI group, the 2-year risk of a target lesion failure was not significantly higher than in the noncomplex PCI group (4.8% vs 3.7%; adjusted hazard ratio: 1.373; 95% confidence interval: 0.689-2.738;Up to 2 years after a ZES implantation, the clinical outcomes did not differ according to lesion complexity.

Background: It is important to determine the best drug-eluting stent (DES) for acute myocardial infarction (AMI) in patients with renal impairment. In this studythe outcomes of everolimus-eluting stents (EESs), zotarolimus-eluting stents (ZESs) and biolimus-eluting stents (BESs) were evaluated. Methods: From the Korea Acute Myocardial Infarction-National Institutes of Health registry, a total of 1,470 AMI patients with renal impairment undergoing percutaneous coronary intervention (PCI) were enrolled (816 with EES, 345 with ZES, and 309 with BES). Renal impairment was defined as creatinine clearance < 60 mL/min/1.73 m 2 estimated by the Cockcroft-Gault method. Major adverse cardiac and cerebrovascular events were determined as the composite of all-cause death, non-fatal myocardial infarction (MI), cerebrovascular accident, any revascularization, rehospitalization and stent thrombosis. All clinical outcomes were analyzed. Results: The baseline characteristics of the patients revealed no significant difference between the three groups, except for Killip classification > 2, beta-blockers, lesion type, vascular approach, staged PCI, left main coronary artery (LMCA) complex lesions, LMCA PCI, and the number and length of implanted stents. In the Kaplan-Meier analysis, similar clinical outcomes were derived from the unadjusted data between the three DES groups. However, after the inverse probability of treatment weighting, a statistically significant difference was found in non-fatal MI, which implied a higher incidence of non-fatal MI in the ZES group than in the other two DES groups. Conclusions: In AMI patients with renal impairment, there was no significant difference between the three stent groups in terms of long-term clinical outcomes, except for non-fatal MI.

Zotarolimus is a semi-synthetic derivative of rapamycin and a novel immunosuppressive agent used to prevent graft rejection. The pharmacological pathway of zotarolimus restricts the kinase activity of the mammalian target of rapamycin (mTOR), which potentially leads to reductions in cell division, cell growth, cell proliferation, and inflammation. These pathways have a critical influence on tumorigenesis. This study aims to examine the anti-tumor effect of zotarolimus or zotarolimus combined with 5-fluorouracil (5-FU) on A549 human lung adenocarcinoma cell line implanted in BALB/c nude mice by estimating tumor growth, apoptosis expression, inflammation, and metastasis. We established A549 xenografts in nude mice, following which we randomly divided the mice into four groups: control, 5-FU (100 mg/kg/week), zotarolimus (2 mg/kg/day), and zotarolimus combined with 5-FU. Compared the results with those for control mice, we found that mice treated with zotarolimus or zotarolimus combined with 5-FU retarded tumor growth, increased tumor apoptosis through the enhanced expression of cleaved caspase 3 and extracellular signal-regulated kinase (ERK) phosphorylation, decreased inflammation cytokines levels (e.g., IL-1β, TNF-α, and IL-6), reduced inflammation-related factors such as cyclooxygenase-2 (COX-2) protein and nuclear factor-κB (NF-κB) mRNA, enhanced anti-inflammation-related factors including IL-10 and inhibitor of NF-κB kinase α (IκBα) mRNA, and inhibited metastasis-related factors such as transforming growth factor β (TGF-β), CD44, epidermal growth factor receptor (EGFR), and vascular endothelial growth factor (VEGF). Notably, mice treated with zotarolimus combined with 5-FU had significantly retarded tumor growth, reduced tumor size, and increased tumor inhibition compared with the groups of mice treated with 5-FU or zotarolimus alone. The in vivo study confirmed that zotarolimus or zotarolimus combined with 5-FU could retard lung adenocarcinoma growth and inhibit tumorigenesis. Zotarolimus and 5-FU were found to have an obvious synergistic tumor-inhibiting effect on lung adenocarcinoma. Therefore, both zotarolimus alone and zotarolimus combined with 5-FU may be potential anti-tumor agents for treatment of human lung adenocarcinoma.

Among drug-eluting stents (DESs), the durable polymer everolimus-eluting stent (EES) and resolute zotarolimus-eluting stent (R-ZES) are widely used in clinical practice and have contributed to improve the outcomes of patients undergoing percutaneous coronary intervention (PCI). Few studies addressed their long-term comparative performance in patients with acute coronary syndrome (ACS). We aimed to investigate the 5 year comparative efficacy of EES and R-ZES in ACS. We queried ACTION-ACS, a large-scale database of ACS patients undergoing PCI. The treatment groups were analyzed using propensity score matching. The primary endpoint was a composite of mortality, myocardial infarction (MI), stroke, repeat PCI, and definite or probable stent thrombosis, which was addressed at the five-year follow-up. A total of 3497 matched patients were analyzed. Compared with R-ZES, a significant reduction in the primary endpoint at 5 years was observed in patients treated with EES (hazard ratio (HR) [95%CI] = 0.62 [0.54–0.71], p &lt, 0.001). By landmark analysis, differences between the two devices emerged after the first year and were maintained thereafter. The individual endpoints of mortality (HR [95%CI] = 0.70 [0.58–0.84], p &lt, 0.01), MI (HR [95%CI] = 0.55 [0.42–0.74], p &lt, 0.001), and repeat PCI (HR [95%CI] = 0.65 [0.53–0.73], p &lt, 0.001) were all significantly lower in the EES-treated patients. Stroke risk did not differ between EES and R-ZES. In ACS, a greater long-term clinical efficacy with EES vs. R-ZES was observed. This difference became significant after the first year of the ACS episode and persisted thereafter.

Background: Uncertainty exists over whether stents commonly used for percutaneous coronary intervention have comparable short- and long-term safety. The objective of this study was to determine the outcomes of patients treated with bioabsorbable polymer everolimus-eluting (BP-EES; Synergy, Boston Scientific), durable polymer everolimus-eluting (DP-EES; XIENCE, Abbott Vascular), or durable polymer zotarolimus-eluting (DP-ZES; Resolute, Medtronic) stents in routine clinical practice. Methods: All percutaneous coronary intervention cases from 48 hospitals performed after the introduction of the BP-EES stent in 2015 until the first quarter of 2018 were included. Propensity-matched multivariable analysis was used to adjust for differences in baseline characteristics and procedural variables. After matching, we performed pair-wise comparisons between DP-EES and BP-EES, DP-EES and DP-ZES, and BP-EES and DP-ZES for in-hospital postpercutaneous coronary intervention outcomes. We also evaluated 2-year postdischarge mortality in a subset of patients who could be matched to Medicare data. Results: During the study period, 53 724 percutaneous coronary intervention cases were performed. A total of 59% of patients were treated with DP-EES stents, 14% with BP-EES stents, and 27% with DP-ZES stents. Although baseline characteristics of patients differed between stent types, these differences were attenuated after matching. In the matched cohort, there was no difference in in-hospital mortality, stent thrombosis, or postprocedural stroke (a falsification end point) between BP-EES, DP-EES, and DP-ZES. After matching, there was no difference in 2-year postdischarge mortality (DP-EES versus BP-EES hazard ratio 0.91, P =0.50; DP-EES versus DP-ZES hazard ratio 1.03, P =0.77; BP-EES versus DP-ZES hazard ratio 1.20, P =0.29). Conclusions: Our data suggest similar risk-adjusted in-hospital outcomes among drug-eluting stent platforms commonly used in clinical practice. The absence of a difference in 2-year mortality between BP-EES, DP-EES, and DP-ZES suggests that stent choice decisions could be made based on other factors, including durability, availability, and cost.

Supplemental Digital Content is available in the text., Background: Despite treatment guidance endorsing shortened dual antiplatelet therapy (DAPT) duration in high bleeding risk (HBR) patients after drug-eluting stents, limited evidence exists to support these recommendations. The present study was designed to examine the safety and effectiveness of 1-month DAPT duration following percutaneous coronary intervention with zotarolimus-eluting stents in HBR patients. Methods: Onyx ONE Clear was a prospective, multicenter, nonrandomized study evaluating the safety and effectiveness of 1-month DAPT followed by single antiplatelet therapy in HBR patients undergoing percutaneous coronary intervention with Resolute Onyx drug-eluting stents. The primary analysis of cardiac death or myocardial infarction between 1 month and 1 year was performed in the prespecified one-month clear population of patients pooled from the Onyx ONE US/Japan study and Onyx ONE randomized controlled trial. One-month clear was defined as DAPT adherence and without major adverse events during the first month following percutaneous coronary intervention. Results: Among patients enrolled in Onyx ONE US/Japan (n=752) and Onyx ONE randomized controlled trial (n=1018), 1506 patients fulfilled one-month clear criteria. Mean HBR characteristics per patient was 1.6 with 44.7% having multiple risks. By 2 months and 1 year, respectively, 96.9% and 89.3% of patients were taking single antiplatelet therapy. Between 1 month and 1 year, the rate of the primary end point was 7.0%. The 1-sided upper 97.5% CI was 8.4%, less than the performance goal of 9.7% (P

Background/Introduction The Onyx ONE Global Study (Onyx ONE), a randomized, single-blind, international trial, demonstrated non-inferiority of a zotarolimus-eluting stent (ZES) to a polymer-free drug-coated stent (DCS) in high-bleeding risk patients treated with 1-month dual antiplatelet therapy (DAPT) followed by single antiplatelet therapy (SAPT). More than half of the Onyx ONE patients presented with an acute coronary syndrome (ACS). The safety and effectiveness of ZES and DCS in ACS patients treated with SAPT after 30 days remains unknown. Purpose To evaluate the safety and effectiveness outcomes for ZES and DCS in Onyx ONE patients presenting with ACS. Methods The primary outcome of the trial was a composite of cardiac death, myocardial infarction, or stent thrombosis at 1 year. To align with the time that DAPT is interrupted, we also evaluated the primary endpoint between the 2 stent groups in a landmark analysis between 30 days and 1 year. All analyses were performed in ACS patients (includes unstable angina, non ST-elevation myocardial infarction and ST-elevation myocardial infarction). Results Among the 1996 patients randomized in Onyx ONE, 982/1902 (51.6%) presented with ACS, of which 511/982 (52.0%) and 471/982 (48.0%) were treated with ZES and DCS respectively. In a pre-defined subgroup analysis in ACS patients, the event rates between the two stent groups regarding the primary outcome at one year were similar (18.5% ZES; 20.8% DCS; HR: 0.91; 95% CI [0.68, 1.22]; p=0.523). In the landmark analysis beyond day 30, the primary outcome rate tended to be lower among those treated with the ZES (8.4%) compared with the DCS (12.1%) [HR: 0.66 (95% CI: 0.43, 1.01), p=0.055] (Figure). This was primarily driven by lower rates of myocardial infarction with ZES (6.5% ZES; 10.2% DCS; [HR: 0.58 (95% CI: 0.36, 0.93); p=0.025], while other components were similar: cardiac death, 2.6% ZES vs. 2.8% DCS [HR: 1.00 (95% CI: 0.44, 2.27); p>0.99) and stent thrombosis, 1.4% ZES vs. 1.4% DCS [HR: 0.93 (95% CI: 0.27, 3.21); p=0.91]. Conclusions In Onyx ONE, high-bleeding risk patients presenting with ACS had similar safety and efficacy at 1 year in both the ZES and DCS stent groups. However, a trend was present for greater safety with the ZES with SAPT treatment beyond 30 days driven by lower myocardial infarction rates in that time period thus warranting additional confirmatory studies. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Medtronic sponsored the Onyx ONE Global Study

Background/Introduction The novel thin composite-wire strut zotarolimus-eluting stent (ZES) is a drug-eluting stent that is frequently used for treating patients with obstructive coronary artery disease, but so far no clinical outcome data have been published in patients with diabetes. In all-comer patients, the BIONYX trial (NCT02508714) has established non-inferiority of the ZES versus the ultrathin strut biodegradable-polymer sirolimus-eluting stent (SES) regarding the primary composite endpoint of target vessel failure at 1 year follow-up. Purpose To assess in patients with diabetes, the 2-year safety and efficacy of the current generation thin composite-wire strut ZES, compared to the ultrathin strut SES. Methods In the international, multicentre BIONYX trial, randomisation was stratified for sex and the presence of diabetes mellitus. We performed a prespecified subgroup analysis of patients with diabetes. The main endpoint target vessel failure was a composite of safety and efficacy, consisting of cardiac death, target vessel-related myocardial infarction or clinically indicated target vessel revascularisation. Secondary endpoints, such as target lesion revascularisation and stent thrombosis were also assessed. Results A total of 510/2488 (20.5%) BIONYX trial participants had diabetes, and were therefore included in this analysis. Patients were on average 66.4±10.3 years old, and 28.6% were female. Most participants presented with acute coronary syndromes (65.1%), and 182/510 (35.7%) patients were insulin dependent. Two-year follow up was available in 500 of 510 (98.0%) patients. Target vessel failure occurred in 31/260 (12.2%) patients assigned to ZES versus 26/250 (10.7%) patients assigned to SES (HR 1.14, 95%-CI 0.68–1.92; P-logrank=0.63). Kaplan Meier curves of target vessel failure are displayed in Figure 1. There were no significant between-stent differences in the individual components of this endpoint. Target lesion revascularisation occurred in 15/260 (6.0%) patients treated with ZES versus 9/250 (3.7%) patients treated with SES (HR 1.61, 95%-CI 0.71–3.68; P-logrank=0.25). Definite stent thrombosis was an infrequent event and did not differ significantly between stent-arms (0.4% vs. 1.2%; HR 0.32, 95%-CI 0.03–3.06; P-logrank=0.30). Conclusion In patients with diabetes, the novel thin composite-wire strut durable polymer ZES was similarly safe and efficacious as compared to the ultrathin cobalt-chromium strut biodegradable-polymer SES at 2-year follow-up. Figure1. Target vessel failure at 2 years Funding Acknowledgement Type of funding source: Private company. Main funding source(s): The BIONYX trial was equally funded by Biotronik and Medtronic.

Background The AngioSculpt X (Spectranetics) is a novel paclitaxel-coated scoring balloon with encouraging preliminary data for the treatment of in-stent restenosis or de novo complex lesions. Purpose To assess the safety and efficacy of real-world patients with in-stent restenosis (ISR) or de novo complex lesions (vessels Methods A “real-world”, prospective registry from two centers was performed including consecutive patients presenting with ISR or de novo complex lesions and treated with AngioSculpt X. Their clinical data were prospectively registered. Major adverse cardiac events (MACE) were defined as a composite of cardiac death, stent thrombosis, nonfatal myocardial infarction, target lesion revascularization (TLR) and target vessel revascularization (TVR). Results Overall, 87 real-world patients and 93 lesions (73% male, 68±10 years, 46% smoker, 83% hypertensive, 62% diabetic, 71% hyperlipidemic, 35% LVEF 1 treatment for ISR. The most frequent artery treated was left anterior descending (41%) followed by left circumflex (35%) and right coronary artery (17%). Quantitative coronary angiography reference diameter of lesions was 2.7±0.5 mm and length 9.0±4.8 mm, with a % stenosis of 75±20. Predilatation/postdilatation was performed in 60/24% respectively. Device diameter was 2.9±0.4 mm and length 13.6±3.9 mm, deployed at 16±3 atmospheres, with an inflation time of 33±16 seconds. The balloon/artery ratio was 0.99±0.03. Crossover was decided on 18 cases (19%) due to remaining intimal flap, but the success rate (residual stenosis Conclusions Paclitaxel-coated scoring balloon offers a safe and valuable treatment option for ISR and de novo complex lesions. Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): Juan Ramόn Jiménez University Hospital

Background Outcome data after extended long-term follow-up of patients with coronary artery disease treated with drug-eluting stents (DES) in randomized clinical trials is scant. Objective Performance differences between devices may be expected to emerge over time depending on whether stenting is done with polymer-free or durable polymer DES. We assessed the 10-year outcomes of patients enrolled in the ISAR-TEST 5 trial. Methods 3002 patients were randomized to treatment with either polymer-free sirolimus- and probucol-eluting stents (PF-SES) (n=2002) or durable polymer zotarolimus-eluting stents (DP-ZES) (n=1000). The primary endpoint was the composite of cardiac death, target vessel-related myocardial infarction or target lesion revascularisation (a device-oriented composite endpoint, DOCE). Additional endpoints of interest were the patient-oriented composite endpoint (POCE), including all-cause death, any myocardial infarction or any revascularisation, individual components of the composite endpoints, and definite or probable stent thrombosis. Results The median age of the patients at randomization was 67.8 years. At 10-years, 63.9% of patients were alive. The rates of DOCE and POCE were high in both groups with no difference in the incidence between PF-SES and DP-ZES, (DOCE: 43.8% versus 43.0%, respectively, hazard ratio = 1.01, 95% CI, 0.89–1.14; P=0.90), (POCE: 66.2% versus 67.7%, respectively, hazard ratio = 0.94, 95%CI, 0.86–1.04; P=0.22). The rates of the individual components of the composite endpoints were comparable in both groups. The incidence of definite/probable stent thrombosis over 10 years was low and comparable in both groups (1.6% vs. 1.9%; hazard ratio = 0.85 [95% CI, 0.46–1.54], P=0.58). Conclusion At 10 years there were no measurable differences in outcomes between patients treated with polymer-free versus durable polymer DES. The incidence of stent thrombosis was low and comparable in both groups. High overall adverse clinical event rates were observed during extended follow-up.

Background: little researches have directly compared second-generation drug-eluting stents with each other or with bare-metal stents. Aim of the work: To compare between outcomes after implantation of bare-metal stents [BMS] and two kinds of 2nd generation drug eluting stents [DES] [Zotarolimus-Eluting Stents [ZES], and A Everolimus-Eluting Stents [EES]] in patients undergoing percutaneous coronary intervention. Patients and Methods: 160 Ischemic Heart Disease [IHD] patients undergoing PCI with 2nd generation DES implantation [80 ZES and 80 EES] were analyzed against 50 IHD patients undergoing PCI with BMS implantation. Each patients group received up to 6 [in BMS group] or 24 months [in ZES and EES groups] of clopidogrel therapy. The key efficacy endpoint was the 24 months major adverse cardiac event [MACE] [death, myocardial infarction, or target lesion revascularization], whereas stent thrombosis [ST] was the safety endpoint. Results: The MACE rate was lowest in EES [19%; χ2= 7.661], highest in BMS [41.7%; χ2 =7.661], and intermediate in ZES [28.2%; χ2= 7.661] group with significant P Value =0.002.The 2-year incidence of ST in the EES group [1.3%] was similar to that in the ZES-S group [2.2%], whereas it was lower in contrast with BMS [7.5%] groups, with significant P value= 0.004]. Conclusion: DES have more efficacy and safety than BMS as EES have lowest MACE and ST rate while BMS have the highest rate and ZES have intermediate rate while the three stent groups have similar rate of mortality at 2 years follow up.

Objectives We sought to evaluate clinical outcomes in patients treated with the drug-eluting stent ihtDEStiny BD. Background The ihtDEStiny BD stent is a metallic sirolimus eluting stent with a biodegradable polymer with both drug and polymer coating the abluminal surface of the stent and balloon. Methods In this study, the clinical outcomes of a multicenter prospective registry of patients treated with this stent (DEStiny group) were analyzed and compared with those of a control group of patients treated with durable polymer everolimus or zotarolimus eluting stents (CONTROL group) paired by propensity score matching . Primary outcome was the target vessel failure (TVF) at 12 months defined as a composite of cardiac death, target vessel myocardial infarction (TV-MI) and target vessel revascularization (TVR). Results A total of 350 patients were included in the DESTtiny group. The control group consisted initially of 1368 patients, but after matching (1:1) 350 patients were selected as CONTROL group. The baseline clinical, angiographic and procedural characteristics were quite comparable in both groups. At 12 months follow up the TVF was 6.6% in DEStiny group and 6.3% in CONTROL group (p = 0.8). No differences were observed for any of the individual components of the primary endpoint: cardiac death 1.1% vs. 1.4%, TV-MI 3.4% vs. 3.7% and TVR 2.6% vs. 2.3% respectively. Conclusions The use of ihtDEStiny stent in real practice is associated with a clinical performance at 12 months follow up that appears to be non-inferior to the most widely used and largely evidence supported durable polymer drug eluting stents. A longer follow up is warranted.

Background: There is limited data comparing the Xience everolimus-eluting stent (EES) and the Resolute zotarolimus-eluting stent (ZES) with the BioMatrix biolimus-eluting stent (BES). Methods: This open-label, randomized, noninferiority trial enrolled all-comer patients to be randomly treated with either BES, EES, or ZES in a 1:1:1 ratio in 15 centers across South Korea. The primary end point was a device-oriented composite outcome consisting of cardiac death, target-vessel myocardial infarction, and clinically indicated target lesion revascularization at 24 months. The BES was compared with the EES and the ZES by intention-to-treat analyses with a noninferiority margin of 3.8%, respectively. Results: Because of slow recruitment and low event rates, this trial was prematurely terminated after enrollment of 1935 (75%) of the intended 2580 patients. Of the 1911 patients randomized to either EES (n=638), BES (n=634), or ZES (n =639), the rate of device-oriented composite outcome was 3.6%, 2.2%, and 3.9%, respectively, at 24 months (BES versus EES: absolute risk difference −1.4% [upper limit of 1-sided 95% CI: −3.2%]; P for noninferiority P for noninferiority Conclusions: The BES was noninferior to either the EES or the ZES in all-comer patients for device-oriented composite outcome at the 24-month follow-up. However, caution is advised regarding interpretation of these results due to the premature termination of this study. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01397175.

Patients with Williams syndrome often present with abnormalities of the vascular wall of the aorta and/or the pulmonary artery. Surgery may result in restenosis of the affected vessel. Herein, we report a case of an infant with multiple recurrences of aortic coarctation successfully treated with Zotarolimus drug-eluting stent.

Objective There is a scarcity of comparative studies between Endeavor Resolute®-zotarolimus-eluting stent (R-ZES) and Resolute Integrity®-ZES (I-ZES) during long-term follow-up periods. Although the stent alloy and the polymer of these two ZESs are similar, the platform and the design of these two stents are different. This study was conducted to compare the efficacy and safety of these two different ZESs in the all-comer Korean patients who underwent percutaneous coronary intervention (PCI) during a 3-year follow-up period. Methods This study was performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki. In this single-center, retrospective, and all-comer patients' cohort study, a total of 889 patients who underwent PCI with R-ZES (n=394) or I-ZES (n=495) were enrolled. The primary endpoint was the occurrence of major adverse cardiac events (MACEs) defined as all-cause death, nonfatal myocardial infarction (MI), any repeat revascularization including target lesion revascularization (TLR), target vessel revascularization (TVR), and non-TVR, and the secondary endpoint was stent thrombosis (ST) at 3 years. Results To adjust for any potential confounders, the propensity score-adjusted multivariable analysis was performed using the logistic regression model (C-statistics=0.689). The cumulative incidence rates of MACEs [adjusted hazard ratio (aHR), 1.341; 95% confidence interval (CI), 0.615-2.922; p=0.461], all-cause death, nonfatal MI, any repeat revascularization, and ST (aHR, 2.090; 95% CI, 0.163-26.77; p=0.571) were similar between the two groups during the 3-year follow-up period. Conclusion R-ZES and I-ZES demonstrated comparable efficacy and safety after PCI during a 3-year follow-up period. However, these results can perhaps be more precisely defined by other large and long-term follow-up studies in the future. (Anatol J Cardiol 2020; 23: 268-76).

International audience; Objectives: To evaluate the independent clinical impact of stent structural features in a large cohort of patients undergoing unprotected left main (ULM) or coronary bifurcation percutaneous coronary intervention (PCI) with a range of very thin strut stents.Background: Clinical impact of structural features of contemporary stents remains to be defined.Methods: All consecutive patients enrolled in the veRy thin stents for patients with left mAIn or bifurcatioN in real life (RAIN) registry were included. The following stent structural features were studied: antiproliferative drugs (everolimus vs. sirolimus vs. zotarolimus), strut material (platinum-chromium vs. cobalt-chromium), polymer (bioresorbable vs. durable), number of crowns (

Introduction: First-generation drug-eluting stents (DES) were developed and indeed proved their superiority compared to bare-metal stent in minimizing neo-intimal hyperplasia and in-stent restenosi...

There are limited data comparing the clinical outcomes among new-generation drug-eluting stents (DES) in acute myocardial infarction (AMI) patients with dyslipidemia after percutaneous coronary intervention (PCI). We thought to investigate 2-year clinical outcomes among durable-polymer (DP)-coated stents [zotarolimus eluting (ZES) and everolimus eluting (EES)] and biodegradable-polymer (BP)-coated biolimus-eluting stent (BES) in dyslipidemic AMI patients after PCI. Finally, a total 2403 enrolled patients were divided into ZES (n = 953), EES (n = 1145) or BES (n = 305) group. The primary endpoint was major adverse cardiac events (MACE) defined as total death (TD), cardiac death (CD), myocardial infarction (MI), target lesion revascularization (TLR), target vessel revascularization (TVR) and non-TVR. The secondary endpoint was the incidence of definite or probable stent thrombosis (ST). The 2-year adjusted hazard ratio (HR) of MACE for ZES vs. EES [HR, 1.066; 95% confidence interval (CI) 0.752-1.511; p = 0.720], ZES vs. BES (HR 0.933; 95% CI 0.565-1.541; p = 0.786), EES vs. BES (HR 1.876; 95% CI 0.535-1.436; p = 0.600) and ZES/EES vs. BES (HR 0.929; 95% CI 0.591-1.462; p = 0.751) was similar. The cumulative incidences of ST were comparable (ZES vs. EES vs. BES = 1.1% vs. 0.9% vs. 1.1%, p = 0.675) and adjusted HR was not different. In addition, the 2-year adjusted HR of TD, CD, MI, TLR, TVR, and non-TVR was similar. The AMI patients with dyslipidemia receiving ZES, EES, or BES after PCI showed comparable safety and efficacy during 2-year follow-up periods. Therefore, DP-DES or BP-DES is equally acceptable in dyslipidemic AMI patients during PCI.

The article looks at the issue of antiproliferative coatings of drug eluting coronary stents from a perspective of their pharmacological properties. Antiproliferative drugs from the “limus” group used in coronary stents do not have decisive advantages over each other. This statement is based on the same pharmacological nature of drugs of the rapamycin group. Regardless of the technology of their creation and the indications for medical use, these drugs have absolutely the same mechanism of pharmacological effects. Currently, all available preparations from the "limus" group satisfy the required pharmacodynamic parameters to achieve a delayed clinical effect in coronary stenting. The coronary stent classification supposes their ranking only by the platform and the eluting system, without taking into account the type of antiproliferative drugs.Received 13 March 2018. Revised 17 April 2018. Accepted 23 April 2018.Funding: The study did not have sponsorship.Conflict of interest: The author declares no conflict of interest.

AIMS The aim of this study was to evaluate the efficacy and safety of the BioNIR stent compared with the Resolute Integrity stent for the treatment of coronary artery disease. METHODS AND RESULTS This first-in-human, multicentre, single-blind randomised non-inferiority trial was performed in Europe and Israel. Patients with stable coronary artery disease or acute coronary syndromes were randomly assigned to treatment with BioNIR or Resolute Integrity stents in a 2:1 fashion. The primary endpoint was angiographic in-stent late lumen loss (LLL) at six months. Three hundred and two patients were randomised, of whom 261 (86.0%) underwent six-month angiographic follow-up. The BioNIR stent was non-inferior to the Resolute Integrity stent for the primary endpoint of in-stent LLL at six months (0.04±0.30 mm vs. 0.03±0.31 mm, respectively, pnoninferiority

Drug-eluting stents revolutionized the treatment of coronary artery disease with vastly improved outcomes compared with bare metal stents. As stent technology has evolved, a wide variety of antiproliferative drugs have been developed to prevent stent restenosis and stent thrombosis. The Resolute stent system (Medtronic, CA, USA) elutes zotarolimus from a multipolymer blend to prevent early and late stent-related complications. The Resolute stents have evolved from the initial Resolute stent, to the Resolute Integrity™ and most recently, the Resolute Onyx™. These stents have been studied across a wide range of patients and coronary syndromes. They compare similarly in performance to their contemporary second generation stents. We present a review of the major trials involving these zotarolimus-eluting stents.

Objectives The study sought to evaluate for the first time the 5-year outcomes after treating an all-comers population with newer-generation cobalt chromium-based Resolute Integrity zotarolimus-eluting stents (ZES) (Medtronic, Santa Rosa, California) versus platinum chromium-based PROMUS Element everolimus eluting stents (EES) (Boston Scientific, Natick, Massachusetts). Background The DUTCH PEERS (TWENTE II) (DUrable polymer-based sTent CHallenge of Promus ElemEnt versus ReSolute integrity: TWENTE II) trial is a randomized, multicenter, single-blinded, investigator-initiated all-comers trial that found at its main analysis similar 1-year safety and efficacy for both drug-eluting stents. It is the first randomized trial ever to investigate the Resolute Integrity ZES and the first trial to compare both devices. Methods In total, 1,811 patients were 1:1 randomized to ZES versus EES. We performed a pre-specified assessment of the 5-year clinical outcomes in terms of safety and efficacy. The main endpoint target vessel failure (TVF) is a composite of cardiac death, target vessel–related myocardial infarction, or target vessel revascularization. Secondary endpoints included the individual components of TVF, and stent thrombosis. The study was independently monitored, and adverse clinical events were independently adjudicated. Results Five-year clinical follow-up data was available in 1,798 (99.3%) patients. The ZES and EES groups showed favorable outcomes, with similar 5-year incidence of TVF (13.2% vs. 14.2%; plog-rank = 0.62) and its individual components: cardiac death (4.5% vs. 4.9%; plog-rank = 0.69), target vessel–related myocardial infarction (3.1% vs. 2.6%; plog-rank = 0.47), and target vessel revascularization (7.6% vs. 8.6%; plog-rank = 0.46). The 5-year incidence of definite or probable stent thrombosis was similar (1.5% vs. 1.3%; plog-rank = 0.83). Conclusions At 5-year follow-up, the Resolute Integrity ZES and PROMUS Element EES showed similar and sustained results in terms of safety and efficacy for treating a broad population of all-comers.

Background: Bone marrow-derived progenitor cells likely contribute to both endothelial- and smooth muscle cell-dependent healing responses in stent-injured vessel sites. This study aimed to assess mobilization of progenitor cells and vessel healing after zotarolimus-eluting (ZES) and everolimus-eluting (EES) stents. Methods and results: In 63 patients undergoing coronary stent implantation, we measured circulating CD34+CD133+CD45low cells and serum levels of biomarkers relevant to stem cell mobilization. In 31 patients of them, we assessed vessel healing within the stented segment using optical coherence tomography (OCT) imaging. The CD34+CD133+CD45low cells increased 68 ± 59% 7 days after bare metal stent (BMS), 10 ± 53% after ZES (P

The efficacy of second‐generation drug‐eluting stents (DES; eg, everolimus and zotarolimus) compared with bare‐metal stents (BMS) in patients undergoing percutaneous coronary intervention was challenged recently by new evidence from large clinical trials. Thus, we aimed to conduct an updated systematic review and meta‐analysis of randomized clinical trials (RCTs) evaluating the efficacy and safety of second‐generation DES compared with BMS. Electronic databases were systematically searched for all RCTs comparing second‐generation DES with BMS and reporting clinical outcomes. The primary efficacy outcome was major adverse cardiac events (MACE); the primary safety outcome was definite stent thrombosis. The DerSimonian and Laird method was used for estimation of summary risk ratios (RR). A total of 9 trials involving 17 682 patients were included in the final analysis. Compared with BMS, second‐generation DES were associated with decreased incidence of MACE (RR: 0.78, 95% confidence interval [CI]: 0.69‐0.88), driven by the decreased incidence of myocardial infarction (MI) (RR: 0.67, 95% CI: 0.48‐0.95), target‐lesion revascularization (RR: 0.47, 95% CI: 0.42‐0.53), definite stent thrombosis (RR: 0.57, 95% CI: 0.41‐0.78), and definite/probable stent thrombosis (RR: 0.54, 95% CI: 0.38‐0.80). The incidence of all‐cause mortality was similar between groups (RR: 0.94, 95% CI: 0.79‐1.10). Meta‐regression showed lower incidences of MI with DES implantation in elderly and diabetic patients (P = 0.026 and P

Aims: A second iteration of a sirolimus-eluting stent (SES) that has a biodegradable PLGA polymer coating with an electrografting base layer on a thin-strut (80 mu m) cobalt-chromium platform (BuMA Supreme; SINOMED, Tianjin, China) has been developed. This first-in-man trial aimed to assess the efficacy and safety of the novel device.Methods and results: This randomised, multicentre, single-blinded, non-inferiority trial compared the BuMA Supreme SES versus a contemporary durable polymer zotarolimus-eluting stent (ZES) in terms of angiographic in-stent late lumen loss (LLL) at nine-month follow-up as the primary endpoint. A total of 170 patients were randomly allocated to treatment with either SES (n=83) or ZES (n=87). At nine-month angiographic follow-up, in-stent LLL was 0.29 +/- 0.33 mm in the SES group and 0.14 +/- 0.37 mm in the ZES group (p(non-inferiority) = 0.45). The in-stent percent diameter stenosis and the binary restenosis rate of the two treatment arms were similar (19.2 +/- 12.0% vs. 16.1 +/- 12.6%, p=0.09, and 3.3% vs. 4.4%, p=1.00, respectively). At 12-month clinical follow-up, there was no difference between treatment arms with regard to the device-oriented composite clinical endpoint (4.9% vs. 5.7%; p=0.72).Conclusions: The PIONEER trial did not meet its primary endpoint in terms of in-stent LLL at ninemonth follow-up. However, this result did not translate into any increase in restenosis rate or impairment in 12-month clinical outcomes.

Zotarolimus is a semi-synthetic derivative of rapamycin and an inhibitor of mammalian target of rapamycin (mTOR) signaling. Currently, zotarolimus is used to prolong the survival time of organ grafts, but it is also a novel immunosuppressive agent with potent anti-proliferative activity. Here, we examine the anti-tumor effect of zotarolimus, alone and in combination with 5-fluorouracil, on HCT-116 colorectal adenocarcinoma cells implanted in BALB/c nude mice. Compared with the control mice, mice treated with zotarolimus or zotarolimus combined with 5-FU showed retarded tumor growth, increased tumor apoptosis through the enhanced expression of cleaved caspase 3 and extracellular signal-regulated kinase (ERK) phosphorylation, reduced inflammation-related factors such as IL-1β, TNF-α, and cyclooxygenase-2 (COX-2) protein, and inhibited metastasis-related factors such as CD44, epidermal growth factor receptor (EGFR), transforming growth factor β (TGF-β), and vascular endothelial growth factor (VEGF). Notably, mice treated with a combination of zotarolimus and 5-FU showed significantly retarded tumor growth, reduced tumor size, and increased tumor inhibition compared with mice treated with 5-FU or zotarolimus alone, indicating a strong synergistic effect. This in vivo study confirms that zotarolimus or zotarolimus combined with 5-FU can be used to retard colorectal adenocarcinoma growth and inhibit tumorigenesis. Our results suggest that zotarolimus may increase the chemo-sensitization of tumor cells. Therefore, zotarolimus alone and zotarolimus combined with 5-FU may be potential anti-tumor agents in the treatment of human colon adenocarcinoma. Future research on zotarolimus may lead to the development of new therapeutic strategies.

Aims The differential impact on ischaemic and bleeding events of the type of drug-eluting stent [durable polymer stents [DES] vs. biodegradable polymer stents vs. bioresorbable scaffolds (BRS)] and length of dual antiplatelet therapy (DAPT) remains to be defined. Methods and results Randomized controlled trials comparing different types of DES and/or DAPT durations were selected. The primary endpoint was Major Adverse Cardiovascular Events (MACE) [a composite of death, myocardial infarction (MI), and target vessel revascularization]. Definite stent thrombosis (ST) and single components of MACE were secondary endpoints. The arms of interest were: BRS with 12 months of DAPT (12mDAPT), biodegradable polymer stent with 12mDAPT, durable polymer stent [everolimus-eluting (EES), zotarolimus-eluting (ZES)] with 12mDAPT, EES/ZES with 12 months of DAPT (DAPT > 12 m). Sixty-four studies with 150 arms and 102 735 patients were included. After a median follow-up of 20 months, MACE rates were similar in the different arms of interest. EES/ZES with DAPT > 12 m reported a lower incidence of MI than the other groups, while BRS showed a higher rate of ST when compared to EES/ZES, irrespective of DAPT length. A higher risk of major bleedings was observed for DAPT > 12 m as compared to shorter DAPT. Conclusion Durable and biodegradable polymer stents along with BRS report a similar rate of MACE irrespective of DAPT length. Fewer MI are observed with EES/ZES with DAPT > 12 m, while a higher rate of ST is reported for BRS when compared to EES/ZES, independently from DAPT length. Stent type may partially affect the outcome together with DAPT length.

Endeavor zotarolimus-eluting stents (E-ZES) and everolimus-eluting stents (EES) as second-generation stents were approved for use in percutaneous coronary interventions (PCIs) in 2008. We aimed to evaluate the long-term outcomes of E-ZES vs. EES using New York State (NYS) cardiac registries and to compare long-term effectiveness of E-ZES vs. EES in six "off-label" and two "high-risk" subgroups.We created a longitudinal database by linking the NYS cardiac registries, the statewide hospital discharge data, the National Death Index, and the U.S. Census file (2010) for patients receiving either E-ZES or EES from July 2008 through December 2010. We examined outcome measures of all-cause mortality, acute myocardial infarction (AMI), target lesion PCI (TLPCI), and target vessel coronary artery bypass graft (TVCABG) surgery for 13,663 propensity score matched pairs in the 6-year follow-up period. We applied Kaplan-Meier methods and Cox proportional hazards regression for further adjustment of propensity-matched pairs.Compared with patients receiving EES, patients receiving E-ZES had a significantly higher rate of 6-year all-cause mortality (adjusted hazard ratio (AHR): 1.10, 95% confidence interval (CI): 1.04-1.17, P=0.003), AMI (AHR: 1.12, 95% CI: 1.02-1.23, P=0.01), TLPCI (AHR: 1.28, 95% CI: 1.18-1.39, P0.001), and TVCABG (AHR: 1.47, 95% CI: 1.26-1.71, P0.001). EES had better or similar long-term outcomes than E-ZES for the subgroups that were examined.At 6years, patients receiving EES generally had better or comparable mortality, AMI, TLPCI, and TVCABG outcomes compared with patients receiving E-ZES.

Background Although studies have demonstrated comparable efficacy and safety profiles of everolimus- and zotarolimus-eluting stents (EES and ZES, respectively) for a broad spectrum of coronary artery diseases, there is paucity of data concerning their safety and efficacy for coronary chronic total occlusions (CTOs). This study compared the clinical performance of EES and ZES following successful percutaneous coronary intervention for CTOs. Methods The cohort included 539 consecutive CTO patients who underwent successful PCI using EES (n=313) and ZES (n=226) between September 2006 and August 2014. The primary outcome was defined as the composite of death, myocardial infarction, and target vessel revascularization. Results During a median follow-up of 3.3years, in both groups, the primary outcome occurred in 12.2% of patients. After multivariable adjustment, no significant difference was observed between the two groups in the risk of primary outcome [hazard ratio (HR) 1.03, 95% confidence interval (CI) 0.59–1.79, P =0.930 for ZES compared with EES]. Similarly, there were no significant differences in the risk of death (adjusted HR 0.96, 95% CI 0.43–2.15, P =925), death or myocardial infarction (adjusted HR 0.93, 95% CI 0.46–1.88, P =0.829), and target vessel failure (adjusted HR 0.96, 95% CI 0.51–1.82, P =0.902). The incidence of definite/probable stent thrombosis was relatively low [0% (ZES) vs. 1.0% (EES), P =0.19]. Conclusion No significant differences were observed between EES and ZES in terms of clinical outcomes for coronary CTOs at 3.3years.

The aim of this study was to explore the safety and efficacy of a dedicated drug-eluting stent for the treatment of coronary lesions with very small reference vessel diameter (RVD).Smaller RVD is associated with increased risk for restenosis and target lesion failure (TLF) after stent implantation.This was a prospective, single-arm, multicenter trial of the Resolute Onyx 2.0-mm zotarolimus-eluting stent. The primary endpoint was 12-month TLF, which was compared with a pre-specified performance goal. Subjects with stable or unstable angina or ischemia, target lesions ≤27 mm in length, and RVD ≥2.0 and 2.25 mm were eligible for enrollment. A subset of subjects underwent follow-up angiography at 13 months post-procedure.A total of 101 subjects with 104 lesions were enrolled. The mean age was 67.3 ± 9.6 years, 47% of subjects had diabetes, the mean lesion length was 12.6 ± 6.3 mm, and the mean RVD was 1.91 ± 0.26 mm. The rate of TLF at 12 months was 5.0%, fulfilling the pre-specified performance goal of 19% (p 0.001). The rates of target lesion revascularization and target vessel myocardial infarction were 2.0% and 3.0%, respectively. There were no episodes of stent thrombosis. In-stent late lumen loss was 0.26 ± 0.48 mm, and the rate of binary restenosis was 12.0%.In this first report of a drug-eluting stent with a dedicated size to treat lesions with RVD 2.25 mm, the Resolute Onyx 2.0-mm zotarolimus-eluting stent was associated with a low rate of TLF and late lumen loss, without a signal for stent thrombosis. This novel-sized drug-eluting stent appears to be a feasible option for the treatment of coronary lesions in extremely small vessels. (Medtronic Resolute Onyx 2.0 mm Clinical Study; NCT02412501).

Several previously published trials comparing Zotarolimus Eluting Stents (ZES) with Sirolimus Eluting Stents (SES), Paclitaxel Eluting Stents (PES) or Everolimus Eluting Stents (EES) at a follow up period of 1 year, were continually being followed up in order to assess the long-term outcomes. In this meta-analysis, we aimed to compare the long-term (2–5 years) adverse clinical outcomes which were associated with ZES versus SES, PES and EES following Percutaneous Coronary Intervention (PCI). Risk Ratios (RR) with 95% Confidence Intervals (CIs) were generated and the analysis was carried out by the RevMan 5.3 software. In this analysis with a total number of 17,606 participants, ZES and EES were associated with similar adverse outcomes including Stent Thrombosis (ST), myocardial infarction (MI), major adverse cardiac events and repeated revascularization. When ZES were compared with SES and PES during the long-term, MI and definite or probable ST were significantly lower with ZES, with RR: 1.35, 95% CI: 1.17–1.56; P = 0.0001 and RR: 1.91, 95% CI: 1.33–2.75; P = 0.0004 respectively whereas the other adverse outcomes were similarly manifested. Future research should be able to confirm this hypothesis.