Biolimus-eluting biodegradable polymer versus sirolimus-eluting permanent polymer stent performance in long lesions: results from the LEADERS multicentre trial substudy

AIMS: Lesion length remains a predictor of target lesion revascularisation and results of long lesion stenting remain poor. Sirolimus-eluting stents have been shown to perform better than paclitaxel eluting stents in long lesions. In this substudy of the LEADERS trial, we compared the performance of biolimus biodegradable polymer (BES) and sirolimus permanent polymer stents (SES) in long lesions. METHODS AND RESULTS: A total of 1,707 'all-comer' patients were randomly allocated to treatment with BES and SES. A stratified analysis of angiographic and clinical outcomes at nine months and one year, respectively was performed for vessels with lesion length <20 mm versus >20 mm (as measured by quantitative angiography).Of 1,707 patients, 592 BES patients with 831 lesions and 619 SES patients with 876 lesions had only short lesions treated. One hundred and fifty-three BES patients with 166 lesions and 151 SES patients with 162 lesions had long lesions. There were no significant differences in baseline clinical characteristics, except for higher number of patients with long lesions presenting with acute myocardial infarction in both stent groups. Long lesions tended to have lower MLD and greater percent diameter stenosis at baseline than short lesions. Late loss was greater for long lesions than short lesions. There was no statistically significant difference in late loss between BES and SES stents (0.32+/-0.69 vs 0.24+/-0.57, p=0.59). Binary in-segment restenosis was present in 23.2% versus 13.1% of long lesions treated with BES and SES, respectively (p=0.042). In patients with long lesions, the overall MACE rate was similar for BES and SES (17% vs 14.6%; p=0.62). There was a trend towards higher overall TLR rate with BES (12.4 % vs 6.0%; HR=2.06; p=0.07) and clinically driven TLR (10.5% vs 5.3%: HR 1.94; p=0.13). Rates of definite stent thrombosis were 3.3% in the long lesion group and 1.3-1.7 % in the short lesion group. CONCLUSIONS: BES and SES appear similar with respect to MACE in long lesions in this "all-comer" patient population. However, long lesions tended to have a higher rate of binary in-segment restenosis and TLR following BES than SES treatment.

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.

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.

Performance of four dentine excavation methods in deciduous teeth

This in vitro study aimed to assess the speed and caries removal effectiveness of four different new and conventional dentine excavation methods. Eighty deciduous molars were assigned to four groups. Teeth were sectioned longitudinally through the lesion centre. Images of one half per tooth were captured by light microscope and confocal laser scanning microscopy (CLSM) to assess the caries extension. The halves were then reassembled and caries removed using round carbide bur (group 1), Er:YAG laser (group 2), hand excavator (group 3) and a polymer bur (group 4). The time needed for the whole excavation in each tooth was registered. After excavation, the halves were photographed by light microscope. Caries extension obtained from CLSM images were superimposed on the post-excavation images, allowing comparison between caries extension and removal. The regions where caries and preparation limits coincided, as well as the areas of over- and underpreparation, were measured. Steel bur was the fastest method, followed by the polymer bur, hand excavator and laser. Steel bur exhibited also the largest overpreparation area, followed by laser, hand excavator and polymer bur. The largest underpreparation area was found using polymer bur, followed by laser, hand excavator and steel bur. Hand excavator presented the longest coincidence line, followed by polymer and steel burs and laser. Overall, hand excavator seemed to be the most suitable method for carious dentine excavation in deciduous teeth, combining good excavation time with effective caries removal.

Supported Cu(II) polymer catalysts for aqueous phenol oxidation

Supported Cu(II) polymer catalysts were used for the catalytic oxidation of phenol at 30 degrees C and atmospheric pressure using air and H(2)O(2) as oxidants. Heterogenisation of homogeneous Cu(II) catalysts was achieved by adsorption of Cu(II) salts onto polymeric matrices (poly(4-vinylpyridine), Chitosan). The catalytic active sites were represented by Cu(II) ions and showed to conserve their oxidative activity in heterogeneous catalysis as well as in homogeneous systems. The catalytic deactivation was evaluated by quantifying released Cu(II) ions in solution during oxidation, from where Cu-PVP(25) showed the best leaching levels no more than 5 mg L(-1). Results also indicated that Cu-PVP(25) had a catalytic activity (56% of phenol conversion when initial Cu(II) catalytic content was 200 mg L(Reaction)(-1)) comparable to that of commercial catalysts (59% of phenol conversion). Finally, the balance between activity and copper leaching was better represented by Cu-PVP(25) due to the heterogeneous catalytic activity had 86% performance in the heterogeneous phase, and the rest on the homogeneous phase, while Cu-PVP(2) had 59% and CuO/gamma-Al(2)O(3) 68%.

Clinical Outcomes According to Diabetic Status in Patients Treated With Biodegradable Polymer Sirolimus-Eluting Stents Versus Durable Polymer Everolimus-Eluting Stents: Prespecified Subgroup Analysis of the BIOSCIENCE Trial.

BACKGROUND Ultrathin strut biodegradable polymer sirolimus-eluting stents (BP-SES) proved noninferior to durable polymer everolimus-eluting stents (DP-EES) for a composite clinical end point in a population with minimal exclusion criteria. We performed a prespecified subgroup analysis of the Ultrathin Strut Biodegradable Polymer Sirolimus-Eluting Stent Versus Durable Polymer Everolimus-Eluting Stent for Percutaneous Coronary Revascularisation (BIOSCIENCE) trial to compare the performance of BP-SES and DP-EES in patients with diabetes mellitus. METHODS AND RESULTS BIOSCIENCE trial was an investigator-initiated, single-blind, multicentre, randomized, noninferiority trial comparing BP-SES versus DP-EES. The primary end point, target lesion failure, was a composite of cardiac death, target-vessel myocardial infarction, and clinically indicated target lesion revascularization within 12 months. Among a total of 2119 patients enrolled between February 2012 and May 2013, 486 (22.9%) had diabetes mellitus. Overall diabetic patients experienced a significantly higher risk of target lesion failure compared with patients without diabetes mellitus (10.1% versus 5.7%; hazard ratio [HR], 1.80; 95% confidence interval [CI], 1.27-2.56; P=0.001). At 1 year, there were no differences between BP-SES versus DP-EES in terms of the primary end point in both diabetic (10.9% versus 9.3%; HR, 1.19; 95% CI, 0.67-2.10; P=0.56) and nondiabetic patients (5.3% versus 6.0%; HR, 0.88; 95% CI, 0.58-1.33; P=0.55). Similarly, no significant differences in the risk of definite or probable stent thrombosis were recorded according to treatment arm in both study groups (4.0% versus 3.1%; HR, 1.30; 95% CI, 0.49-3.41; P=0.60 for diabetic patients and 2.4% versus 3.4%; HR, 0.70; 95% CI, 0.39-1.25; P=0.23, in nondiabetics). CONCLUSIONS In the prespecified subgroup analysis of the BIOSCIENCE trial, clinical outcomes among diabetic patients treated with BP-SES or DP-EES were comparable at 1 year. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01443104.

Ultrathin Strut Biodegradable Polymer Sirolimus-Eluting Stent Versus Durable-Polymer Everolimus-Eluting Stent for Percutaneous Coronary Revascularization: 2-Year Results of the BIOSCIENCE Trial.

BACKGROUND No data are available on the long-term performance of ultrathin strut biodegradable polymer sirolimus-eluting stents (BP-SES). We reported 2-year clinical outcomes of the BIOSCIENCE (Ultrathin Strut Biodegradable Polymer Sirolimus-Eluting Stent Versus Durable Polymer Everolimus-Eluting Stent for Percutaneous Coronary Revascularisation) trial, which compared BP-SES with durable-polymer everolimus-eluting stents (DP-EES) in patients undergoing percutaneous coronary intervention. METHODS AND RESULTS A total of 2119 patients with minimal exclusion criteria were assigned to treatment with BP-SES (n=1063) or DP-EES (n=1056). Follow-up at 2 years was available for 2048 patients (97%). The primary end point was target-lesion failure, a composite of cardiac death, target-vessel myocardial infarction, or clinically indicated target-lesion revascularization. At 2 years, target-lesion failure occurred in 107 patients (10.5%) in the BP-SES arm and 107 patients (10.4%) in the DP-EES arm (risk ratio [RR] 1.00, 95% CI 0.77-1.31, P=0.979). There were no significant differences between BP-SES and DP-EES with respect to cardiac death (RR 1.01, 95% CI 0.62-1.63, P=0.984), target-vessel myocardial infarction (RR 0.91, 95% CI 0.60-1.39, P=0.669), target-lesion revascularization (RR 1.17, 95% CI 0.81-1.71, P=0.403), and definite stent thrombosis (RR 1.38, 95% CI 0.56-3.44, P=0.485). There were 2 cases (0.2%) of definite very late stent thrombosis in the BP-SES arm and 4 cases (0.4%) in the DP-EES arm (P=0.423). In the prespecified subgroup of patients with ST-segment elevation myocardial infarction, BP-SES was associated with a lower risk of target-lesion failure compared with DP-EES (RR 0.48, 95% CI 0.23-0.99, P=0.043, Pinteraction=0.026). CONCLUSIONS Comparable safety and efficacy profiles of BP-SES and DP-EES were maintained throughout 2 years of follow-up. CLINICAL TRIAL REGISTRATION URL: https://www.clinicaltrials.gov. Unique identifier: NCT01443104.