The three year follow-up of the randomised "all-comers" trial of a biodegradable polymer biolimus-eluting stent versus permanent polymer sirolimus-eluting stent (LEADERS)

Aims: The current study reports clinical outcomes at three year follow-up of the LEADERS clinical trial which was the first all-comers trial comparing a new generation biodegradable polymer biolimus drug-eluting stent (BES) with the first generation permanent polymer sirolimus-eluting stent (SES). Methods and results: One thousand seven hundred and seven patients were randomised to unrestricted use of BES (n=857) or SES (n=850) in an all-comers population. Three year follow-up was available in 95% of the patients, 812 treated with BES and 809 treated with SES. At three years, BES remains non-inferior to SES for the primary endpoint of major adverse cardiac events (composite of cardiac death, myocardial infarction (MI), or clinically-indicated target vessel revascularisation (CI-TVR) (BES 15.7% versus SES 19%; HR 0.82 CI 0.65-1.03; p=0.09). The MACE Kaplan Meier event curves increasingly diverge with the difference in events increasing from 1.4% to 2.4% and 3.3% at 1, 2 and 3 years, respectively in favour of BES. The rate of cardiac death was non-significantly lower 4.2% versus 5.2% (HR=0.81 CI 0.52-1.26; p=0.34) and the rate of myocardial infarction was equivalent 7.2% versus 7.1% (HR 1.01 CI 0.70-1.44; p=0.97) for BES versus SES, respectively. Thus BES was non-inferior to SES in all the safety endpoints. Clinically-indicated TVR occurred in 9.4% of BES treated patients versus 11.1% of SES treated patients (HR 0.84 CI 0.62-1.13; p=0.25). Rates of definite stent thrombosis were 2.2% for BES and 2.9% for SES (HR 0.78 CI 0.43-1.43; p=0.43), with the event rate increase of 0.2% from one to three years for BES and 0.9% for SES. For patients presenting with ST-elevation myocardial infarction BES was superior to SES in reducing MACE. Conclusions: The findings of the three year follow-up support the claim that the biodegradable polymer biolimus-eluting stent has equivalent safety and efficacy to permanent polymer sirolimus-eluting stent in an all-comers patient population. Its performance is superior in some subpopulations such as in ST-elevation MI patients and event rates for BES are overall lower than for SES with a trend toward increasing divergence of outcomes over three years. - See more at: http://www.pcronline.com/eurointervention/42nd_issue/125/#sthash.E5HhMQ4a.dpuf

Implantation of the biodegradable polymer biolimus-eluting stent in patients with high SYNTAX score is associated with decreased cardiac mortality compared to a permanent polymer sirolimus-eluting stent: two year follow-up results from the "all-comers" LEADERS trial

Background: The SYNTAX score (SXscore) has been shown to be an effective predictor of clinical outcomes in patients undergoing percutaneous coronary intervention (PCI). Methods and results: The SXscore was prospectively collected in 1,397 of the 1,707 patients enrolled in the “all-comers” LEADERS trial (patients post-surgical revascularisation were excluded). Post hoc analysis was performed by stratifying clinical outcomes at two-year follow-up, according to one of three SXscore tertiles: SXlow ≤8 (n=464), 816 (n=461). At two-year follow-up the rate of major adverse cardiovascular events was 18.4%, 12.0% and 9.4% in the SXhigh, SXmid, and SXlow tertile, respectively (HR 1.45; CI 1.21-1.74; p<0.01). There was a significantly higher rate of cardiac death in patients in the highest SXscore tertile (7% SXhigh versus 2.4% SXmid versus 1.8% SXlow; HR 2.22; CI 1.5-3.27; p<0.001). Within the SXhigh tertile the rate of cardiac death was significantly lower in patients treated with the biolimus-eluting stent compared with the sirolimus-eluting stent (4.7% versus 9.6%, HR 0.48; CI 0.23-0.99; p=0.046). Conclusions: The SXscore when applied to an “all-comers” patient population allows for prospective risk stratification of patients undergoing PCI up to two years follow-up. In addition, the SXscore appears to separate the performance of devices in high risk patient groups.

Two-year clinical follow-up from the randomized comparison of biolimus-eluting stents with biodegradable polymer and sirolimus-eluting stents with durable polymer in routine clinical practice

Objectives This study sought to investigate safety and efficacy of biolimus-eluting stents (BES) with biodegradable polymer as compared with sirolimus-eluting stents (SES) with durable polymer through 2 years of follow-up. Background BES with a biodegradable polymer provide similar efficacy and safety as SES with a durable polymer at 9 months. Clinical outcomes beyond the period of biodegradation of the polymer used for drug release and after discontinuation of dual antiplatelet therapy are of particular interest. Methods A total of 1,707 patients were randomized to unrestricted use of BES (n = 857) or SES (n = 850) in an all-comers patient population. Results At 2 years, BES remained noninferior compared with SES for the primary endpoint, which was a composite of cardiac death, myocardial infarction, or clinically indicated target vessel revascularization (BES 12.8% vs. SES 15.2%, hazard ratio [HR]: 0.84, 95% confidence interval [CI]: 0.65 to 1.08, pnoninferiority < 0.0001, psuperiority = 0.18). Rates of cardiac death (3.2% vs. 3.9%, HR: 0.81, 95% CI: 0.49 to 1.35, p = 0.42), myocardial infarction (6.3% vs. 5.6%, HR: 1.12, 95% CI: 0.76 to 1.65, p = 0.56), and clinically indicated target vessel revascularization (7.5% vs. 8.6%, HR: 0.86, 95% CI: 0.62 to 1.20, p = 0.38) were similar for BES and SES. The rate of definite stent thrombosis through 2 years was 2.2% for BES and 2.5% for SES (p = 0.73). For the period between 1 and 2 years, event rates for definite stent thrombosis were 0.2% for BES and 0.5% for SES (p = 0.42). After discontinuation of dual antiplatelet therapy, no very late definite stent thrombosis occurred in the BES group. Conclusions At 2 years of follow-up, the unrestricted use of BES with a biodegradable polymer maintained a similar safety and efficacy profile as SES with a durable polymer. (Limus Eluted From a Durable Versus Erodable Stent Coating [LEADERS]; NCT00389220)

Tissue coverage of a hydrophilic polymer-coated zotarolimus-eluting stent vs. a fluoropolymer-coated everolimus-eluting stent at 13-month follow-up: an optical coherence tomography substudy from the RESOLUTE All Comers trial

Aims To compare the tissue coverage of a hydrophilic polymer-coated zotarolimus-eluting stent (ZES) vs. a fluoropolymer-coated everolimus-eluting stent (EES) at 13 months, using optical coherence tomography (OCT) in an ‘all-comers' population of patients, in order to clarify the mechanism of eventual differences in the biocompatibility and thrombogenicity of the devices. Methods and results Patients randomized to angiographic follow-up in the RESOLUTE All Comers trial (NCT00617084) at pre-specified OCT sites underwent OCT follow-up at 13 months. Tissue coverage and apposition were assessed strut by strut, and the results in both treatment groups were compared using multilevel logistic or linear regression, as appropriate, with clustering at three different levels: patient, lesion, and stent. Fifty-eight patients (30 ZES and 28 EES), 72 lesions, 107 stents, and 23 197 struts were analysed. Eight hundred and eighty-seven and 654 uncovered struts (7.4 and 5.8%, P= 0.378), and 216 and 161 malapposed struts (1.8 and 1.4%, P= 0.569) were found in the ZES and EES groups, respectively. The mean thickness of coverage was 116 ± 99 µm in ZES and 142 ± 113 µm in EES (P= 0.466). No differences in per cent neointimal volume obstruction (12.5 ± 7.9 vs. 15.0 ± 10.7%) or other areas–volumetric parameters were found between ZES and EES, respectively. Conclusion No significant differences in tissue coverage, malapposition, or lumen/stent areas and volumes were detected by OCT between the hydrophilic polymer-coated ZES and the fluoropolymer-coated EES at 13-month follow-up.

Biodegradable polymer drug-eluting stents reduce the risk of stent thrombosis at 4 years in patients undergoing percutaneous coronary intervention: a pooled analysis of individual patient data from the ISAR-TEST 3, ISAR-TEST 4, and LEADERS randomized trials

The efficacy of durable polymer drug-eluting stents (DES) is delivered at the expense of delayed healing of the stented vessel. Biodegradable polymer DES aim to avoid this shortcoming and may potentially improve long-term clinical outcomes, with benefit expected to accrue over time. We sought to compare long-term outcomes in patients treated with biodegradable polymer DES vs. durable polymer sirolimus-eluting stents (SES).

Two-Dimensional Manganese(II) Coordination Polymer Based on Phthalate and Pyrazine Bridges Exhibiting Antiferromagnetic Porperties

Benzodifuran-functionalised pyrene and anthracene fluorophores 1 and 2 were obtained in reasonable yields. Their single crystal structures, electrochemical, optical absorption, and fluorescence characteristics have been described. They show strong luminescence with high quantum yields of 0.53 for 1 and 0.48 for 2. Magnetic measurements for the 2D coordination polymer [Mn(Pht(Pyz(H2O)2]n (1), in which metal centres are linked together by pyrazine (Pyz) and 1,6-bridging o-phthalate ligand (Pht2-), revealed antiferromagnetic interactions between Mn(II) ions.

Effect of biolimus-eluting stents with biodegradable polymer vs bare-metal stents on cardiovascular events among patients with acute myocardial infarction: the COMFORTABLE AMI randomized trial

The efficacy and safety of drug-eluting stents compared with bare-metal stents remains controversial in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI).

Solid-State Compatibilization of Immiscible Polymer Blends: Cryogenic Milling and Solid-State Shear Pulverization

The blending of common polymers allows for the rapid and facile synthesis of new materials with highly tunable properties at a fraction of the costs of new monomer development and synthesis. Most blends of polymers, however, are completely immiscible and separate into distinct phases with minimal phase interaction, severelydegrading the performance of the material. Cross-phase interactions and property enhancement can be achieved with these blends through reactive processing or compatibilizer addition. A new class of blend compatibilization relies on the mechanochemical reactions between polymer chains via solid-state, high energy processing. Two contrasting mechanochemical processing techniques are explored in this thesis: cryogenic milling and solid-state shear pulverization (SSSP). Cryogenic milling is a batch process where a milling rod rapidly impacts the blend sample while submerged within a bath of liquid nitrogen. In contrast, SSSP is a continuous process where blend components are subjected to high shear and compressive forces while progressing down a chilled twin-screw barrel. In the cryogenic milling study, through the application of a synthesized labeledpolymer, in situ formation of copolymers was observed for the first time. The microstructures of polystyrene/high-density polyethylene (PS/HDPE) blends fabricated via cryomilling followed by intimate melt-state mixing and static annealing were found to be morphologically stable over time. PS/HDPE blends fabricated via SSSP also showed compatibilization by way of ideal blend morphology through growth mechanisms with slightly different behavior compared to the cryomilled blends. The new Bucknell University SSSP instrument was carefully analyzed and optimized to produce compatibilized polymer blends through a full-factorial experiment. Finally, blends of varying levels of compatibilization were subjected to common material tests to determine alternative means of measuring and quantifying compatibilization,

Characterization of Biodegradable Polymer Nanocomposites Fabricated via Solid-State Processing

Biodegradable polymer/clay nanocomposites were prepared withpristine and organically modified montmorillonite in polylactic acid (PLA) and polycaprolactone (PCL) polymer matrices. Nanocomposites were fabricated using extrusion and SSSP to compare the effects of melt-state and solid-state processing on the morphology of the final nanocomposite. Characterization of various material properties was performed on prepared biodegradable polymer/clay nanocomposites to evaluate property enhancements from different clays and/or processing methods.

A fluorescently labeled dendronized polymer-enzyme conjugate carrying multiple copies of two different types of active enzymes

A hybrid structure of a synthetic dendronized polymer, two different types of enzymes (superoxide dismutase and horseradish peroxidase), and a fluorescent dye (fluorescein) was synthesized. Thereby, a single polymer chain carried multiple copies of the two enzymes and the fluorescein. The entire attachment chemistry is based on UV/vis-quantifiable bis-aryl hydrazone bond formation that allows direct quantification of bound molecules: 60 superoxide dismutase, 120 horseradish peroxidase, and 20 fluorescein molecules on an average polymer chain of 2000 repeating units. To obtain other enzyme ratios the experimental conditions were altered accordingly. Moreover, it could be shown that both enzymes remained fully active and catalyzed a two-step cascade reaction.

Polymer stent coating for prevention of neointimal hyperplasia

AIMS: Restenosis has been the principal limitation of bare metal stents. Based upon the presumption that platelet and inflammatory cell recruitment initiate neointimal proliferation, we explored a novel polymer coating that reduces cell-stent interactions. The purpose of the present study was to investigate the effect of poly(L-lysine)-graft-poly(ethyleneglycol) (PLL-g-PEG) adsorbed to stent surfaces to reduce neointimal hyperplasia in the porcine restenosis model. METHODS AND RESULTS: Seven animals were instrumented each with 2 stainless steel stents (15 mm length, 2.5-3.5 mm diameter), randomly implanted in 1 major epicardial coronary artery. One stent was dip-coated with PLL-g-PEG, whereas the other stent served as the uncoated control stent. All animals were sacrificed after 6 weeks for histological examination. Neointimal hyperplasia was significantly less (-51%) in the PLL-g-PEG-coated stents (1.15 +/- 0.59 mm2) than in the uncoated control stents (2.33 +/- 1.01 mm2; p < 0.001). Conversely, lumen size was larger in the PLL-g-PEG-coated stents (2.91 +/- 1.17 mm2) than in the uncoated stents (2.04 +/- 0.64 mm2; p < 0.001). High magnification histomorphologic examination revealed no signs of inflammation or thrombus formation in either stent group. CONCLUSIONS: Polymeric steric stabilization of stents with PLL-g-PEG significantly reduces neointimal hyperplasia in the porcine restenosis model. Reduction of cell-stent interactions mediated by PLL-g-PEG appear to improve biocompatibility of stainless steel stents without evidence of adverse inflammatory or prothrombotic effects.

The long-term mechanical integrity of non-reinforced PEEK-OPTIMA polymer for demanding spinal applications: experimental and finite-element analysis

Polyetheretherketone (PEEK) is a novel polymer with potential advantages for its use in demanding orthopaedic applications (e.g. intervertebral cages). However, the influence of a physiological environment on the mechanical stability of PEEK has not been reported. Furthermore, the suitability of the polymer for use in highly stressed spinal implants such as intervertebral cages has not been investigated. Therefore, a combined experimental and analytical study was performed to address these open questions. A quasi-static mechanical compression test was performed to compare the initial mechanical properties of PEEK-OPTIMA polymer in a dry, room-temperature and in an aqueous, 37 degrees C environment (n=10 per group). The creep behaviour of cylindrical PEEK polymer specimens (n=6) was measured in a simulated physiological environment at an applied stress level of 10 MPa for a loading duration of 2000 hours (12 weeks). To compare the biomechanical performance of different intervertebral cage types made from PEEK and titanium under complex loading conditions, a three-dimensional finite element model of a functional spinal unit was created. The elastic modulus of PEEK polymer specimens in a physiological environment was 1.8% lower than that of specimens tested at dry, room temperature conditions (P<0.001). The results from the creep test showed an average creep strain of less than 0.1% after 2000 hours of loading. The finite element analysis demonstrated high strain and stress concentrations at the bone/implant interface, emphasizing the importance of cage geometry for load distribution. The stress and strain maxima in the implants were well below the material strength limits of PEEK. In summary, the experimental results verified the mechanical stability of the PEEK-OPTIMA polymer in a simulated physiological environment, and over extended loading periods. Finite element analysis supported the use of PEEK-OPTIMA for load-bearing intervertebral implants.