Comparison of eligible non-enrolled patients and the randomised TWENTE trial population treated with Resolute and XIENCE V drug-eluting stents

Aims: The TWENTE trial recently enrolled more than 80% of all eligible patients, who were randomised to zotarolimus-eluting Resolute or everolimus-eluting XIENCE V stents. In the present study, we investigated whether eligible, non-enrolled patients differed from the randomised TWENTE trial population in baseline characteristics and one-year outcome. Methods and results: Characteristics of 1,709 eligible patients were analysed. Independent external adjudication of clinical events was likewise performed for non-enrolled (n=318) and randomised patients (n=1,391). Non-enrolled and randomised patients did not differ in gender distribution, diabetes mellitus, and clinical presentation, but differed significantly in age and cardiovascular history. Nevertheless, clinical outcome after one year did not differ in the primary composite endpoint target-vessel failure (TVF; 9.8% vs. 8.1%; p=0.34), and its components cardiac death (1.6% vs. 1.2%; p=0.61), target vessel-related myocardial infarction (4.7% vs. 4.6%; p=0.92), and target-vessel revascularisation (3.8% vs. 3.0%; p=0.48). Previous bypass surgery predicted TVF in non-enrolled patients (p=0.001); removal of these patients resulted in identical TVF rates for non-enrolled and randomised patients (7.3% vs. 7.3%; p=0.99). Conclusions: Despite some differences in baseline characteristics, non-enrolled and randomised patients did not differ in one-year outcome, which was favourable for both populations and may be related to the drug-eluting stents used

TCT-47 Two-Year Clinical Outcome of the TWENTE Trial, a Randomized Controlled Trial Comparing Second-Generation Zotarolimus-Eluting Resolute Stents Versus Everolimus-Eluting Xience V Stents in Real-World Patients

Background: In the prospective, randomized TWENTE trial, the zotarolimus-eluting Resolute stent was at 1 year follow-up non-inferior to the everolimus-eluting Xience V stent for the primary endpoint target vessel failure. This composite endpoint consisted of cardiac death, clinically indicated target vessel revascularization, or target vessel-related myocardial infarction (MI). So far, few long-term data of prospective head-to-head comparisons between both DES have been reported. Methods: Patients requiring percutaneous coronary interventions (PCI) with DES implantation at Thoraxcentrum Twente in Enschede were randomization between Resolute (Medtronic Vascular, Santa Rosa, CA, USA) and Xience V (Abbott Vascular, Santa Clara, CA, USA) in a 1:1 fashion. Inclusion of all coronary or bypass graft lesions and all clinical settings was permitted except for primary PCI (i.e. acute ST-elevation myocardial infarction (STEMI) was an exclusion criterion). Both external monitoring and clinical event adjudication were performed by an independent external contract research organization (Cardialysis, Rotterdam, the Netherlands). Two year clinical follow-up was performed as indicated in the study protocol. Results: A total of 1,391 patients were enrolled in the TWENTE trial between June 2008 and August 2010. The study population comprised 21.6% diabetics with a vast majority of complex lesions and “off-label” indications for drug-eluting stents (77.4%). Patients presented with either stable angina (48.5%) or unstable angina/Non-STEMI (51.5%). Demographics, baseline angiographic and procedural data, and 2-year clinical follow-up data will be presented. This includes the primary endpoint of the study: Target vessel failure (TVF) at 2 year follow-up. Secondary endpoints include the individual components of the primary endpoint and the incidence of very late stent thrombosis. In addition, results of subgroup analyses will be reported. Conclusions: Results of pre-specified analyses of 2-year clinical outcome of the TWENTE trial will be presented at TCT 2012

A Randomized Controlled Trial in Second-Generation Zotarolimus-Eluting Resolute Stents Versus Everolimus-Eluting Xience V Stents in Real-World Patients : The TWENTE Trial

ObjectivesThe aim of this study was to compare the safety and efficacy of Resolute zotarolimus-eluting stents (ZES) (Medtronic Cardiovascular, Santa Rosa, California) with Xience V everolimus-eluting stents (EES) (Abbott Vascular Devices, Santa Clara, California) at 1-year follow-up.BackgroundOnly 1 randomized trial previously compared these stents.MethodsThis investigator-initiated, patient-blinded, randomized noninferiority study had limited exclusion criteria (acute ST-segment elevation myocardial infarctions not eligible). Patients (n = 1,391; 81.4% of eligible population) were randomly assigned to ZES (n = 697) or EES (n = 694). Liberal use of stent post-dilation was encouraged. Cardiac biomarkers were systematically assessed. The primary endpoint was target vessel failure (TVF), a composite of cardiac death, myocardial infarction not clearly attributable to non-target vessels, and clinically indicated target-vessel revascularization. An external independent research organization performed clinical event adjudication (100% follow-up data available). Analysis was by intention-to-treat.ResultsAcute coronary syndromes were present in 52% and “off-label” feature in 77% of patients. Of the lesions, 70% were type B2/C; the post-dilation rate was very high (82%). In ZES and EES, TVF occurred in 8.2% and 8.1%, respectively (absolute risk-difference 0.1%; 95% confidence interval: −2.8% to 3.0%, pnoninferiority = 0.001). There was no significant between-group difference in TVF components. The definite-or-probable stent thrombosis rates were relatively low and similar for ZES and EES (0.9% and 1.2%, respectively, p = 0.59). Definite stent thrombosis rates were also low (0.58% and 0%, respectively, p = 0.12). In EES, probable stent thrombosis beyond day 8 was observed only in patients not adhering to dual antiplatelet therapy.ConclusionsResolute ZES were noninferior to Xience V EES in treating “real-world” patients with a vast majority of complex lesions and “off-label” indications for drug-eluting stents, which were implanted with liberal use of post-dilation. (The Real-World Endeavor Resolute Versus XIENCE V Drug-Eluting SteNt Study: Head-to-head Comparison of Clinical Outcome After Implantation of Second Generation Drug-eluting Stents in a Real World Scenario; NCT01066650

Clinical Outcome Following Stringent Discontinuation of Dual Antiplatelet Therapy After 12 Months in Real-World Patients Treated With Second-Generation Zotarolimus-Eluting Resolute and Everolimus-Eluting Xience V Stents : 2-Year Follow-Up of the Randomized TWENTE Trial

Objectives The aim of this study was to assess the safety and efficacy of the implantation of Resolute zotarolimus-eluting stents (ZES) (Medtronic Inc., Santa Rosa, California) and Xience V everolimus-eluting stents (EES) (Abbott Vascular, Santa Clara, California) following strict discontinuation of dual antiplatelet therapy (DAPT) after 12 months. Background Only limited long-term follow-up data are available from head-to-head comparisons of second-generation drug-eluting stents. Methods The randomized TWENTE (The Real-World Endeavor Resolute Versus Xience V Drug-Eluting Stent Study in Twente) trial is an investigator-initiated study performed in a population with many complex patients and lesions and only limited exclusion criteria. Patients were randomly assigned 1:1 to ZES (n = 697) or EES (n = 694). Results Two-year follow-up information was available on all patients. The rate of continuation of DAPT beyond 12 months was very low (5.4%). The primary endpoint of target vessel failure, a composite of cardiac death, target vessel–related myocardial infarction, and target vessel revascularization, did not differ between ZES and EES (10.8% vs. 11.6, p = 0.65), despite fewer target lesion revascularizations in patients with EES (2.6% vs. 4.9%, p = 0.03). The patient-oriented composite endpoint was similar (16.4% vs. 17.1%, p = 0.75). Two-year rates of definite or probable stent thrombosis were 1.2% and 1.4%, respectively (p = 0.63). Very late definite or probable stent thrombosis occurred only in 2 patients in each study arm (0.3% vs. 0.3%, p = 1.00). Conclusions After 2 years of follow-up and stringent discontinuation of DAPT beyond 12 months, Resolute ZES and Xience V EES showed similar results in terms of safety and efficacy for treating patients with a majority of complex lesions and off-label indications for drug-eluting stents. (The Real-World Endeavor Resolute Versus Xience V Drug-Eluting Stent Study in Twent

Kinetics of the incorporation of dietary fatty acids into serum cholesteryl esters, erythrocyte membranes, and adipose tissue: an 18-month controlled study.

Tissue levels of n-3 fatty acids reflect dietary intake, but quantitative data about rate of incorporation and levels as a function of intake are scarce. We fed 58 men 0, 3, 6, or 9 g/d of fish oil for 12 months and monitored fatty acids in serum cholesteryl esters, erythrocytes, and subcutaneous fat during and after supplementation. Eicosapentaenoic acid (EPA) in cholesteryl esters plateaued after 4-8 weeks; the incorporation half-life was 4.8 days. Steady-state levels increased by 3.9 /- 0.3 mass % points ( /- SE) for each extra gram of EPA eaten per day. Incorporation of docosahexaenoic acid (DHA) was erratic; plateau values were 1.1 /- 0.1 mass % higher for every g/d ingested. Incorporation of EPA into erythrocyte membranes showed a half- life of 28 days; a steady state was reached after 180 days. Each g/d increased levels by 2.1 /- 0.1 mass %. C22:5n-3 levels increased markedly. Changes in DHA were erratic and smaller. EPA levels in adipose tissue rose also; the change after 6 months was 67% of that after 12 months in gluteal and 75% in abdominal fat. After 12 months each gram per day caused an 0.11 /- 0.01 mass % rise in gluteal fat for EPA, 0.53 /- 0.07 for C22:5n-3, and 0.14 /- 0.03 for DHA. Thus, different (n-3) fatty acids were incorporated with different efficiencies, possibly because of interconversions or different affinities of the enzymatic pathways involved. EPA levels in cholesteryl esters reflect intake over the past week or two, erythrocytes over the past month or two, and adipose tissue over a period of years. These findings may help in assessing the intake of (n- 3) fatty acids in epidemiological studies

Early Bayesian modeling of a potassium lab-on-a-chip for monitoring of heart failure patients at increased risk of hyperkalaemia.

Objectives: Innovative point-of-care (POC) diagnostics are likely to have a strong impact on 18 health care. The aim of this study is to conduct an early assessment of a point-of-care chip 19 for the detection of a pathological deviation of the potassium levels in patients at increased 20 risk, specifically in patients with heart failure (HF) requiring diuretics and ACE inhibitors that 21 can both interfere with potassium levels, which may lead to serious clinical complications. This 22 study also identifies the key factors that determine the success of the application under study. 23 Methods: AMarkov health state transitionmodelwas developed representing the disease process. 24\ud Model parameters were obtained from various literature sources and estimated using interviews 25 and related data. Simulationwas carried out for 60 cycles of 1 month each. A discount rate of 3.5% 26 was used, both for costs and utilities. In order to assess uncertainty a probabilistic sensitivity anal- 27\ud ysis was carried out from which a cost-effectiveness acceptability curve was derived. 28 Results: For an anticipated number of 121 measurements per year with a cost of €16.60 per chip, 29 an incremental cost-effectiveness ratio (ICER) of 34,856 €/QALY was found. Sensitivity analysis 30\ud revealed that the threshold for the costs per chip was €19.30 in order to maintain a positive 31 net monetary benefit. Also, model results are very sensitive to the utility of hyperkalaemia and 32 to the probability to develop severe hyperkalaemia. 33 Conclusions: The question whether or not a POC chip to measure potassium concentrations in 34 order to avoid a severe potassium imbalance is likely to be cost-effective cannot be definitively 35 answered with the information at our disposal. Further research should focus on heart HF 36 patients at particularly high risk of severe life-threatening hyperkalaemia, for instance in the 37 presence of significant renal dysfunction. It may be expected that the use of the chip in such 38 patient populations may render this point-of-care application very cost-effectiv

Kinetics of the incorporation of dietary fatty acids into serum cholesteryl esters, erythrocyte membranes, and adipose tissue: an 18-month controlled study.

Tissue levels of n-3 fatty acids reflect dietary intake, but quantitative data about rate of incorporation and levels as a function of intake are scarce. We fed 58 men 0, 3, 6, or 9 g/d of fish oil for 12 months and monitored fatty acids in serum cholesteryl esters, erythrocytes, and subcutaneous fat during and after supplementation. Eicosapentaenoic acid (EPA) in cholesteryl esters plateaued after 4-8 weeks; the incorporation half-life was 4.8 days. Steady-state levels increased by 3.9 /- 0.3 mass % points ( /- SE) for each extra gram of EPA eaten per day. Incorporation of docosahexaenoic acid (DHA) was erratic; plateau values were 1.1 /- 0.1 mass % higher for every g/d ingested. Incorporation of EPA into erythrocyte membranes showed a half- life of 28 days; a steady state was reached after 180 days. Each g/d increased levels by 2.1 /- 0.1 mass %. C22:5n-3 levels increased markedly. Changes in DHA were erratic and smaller. EPA levels in adipose tissue rose also; the change after 6 months was 67% of that after 12 months in gluteal and 75% in abdominal fat. After 12 months each gram per day caused an 0.11 /- 0.01 mass % rise in gluteal fat for EPA, 0.53 /- 0.07 for C22:5n-3, and 0.14 /- 0.03 for DHA. Thus, different (n-3) fatty acids were incorporated with different efficiencies, possibly because of interconversions or different affinities of the enzymatic pathways involved. EPA levels in cholesteryl esters reflect intake over the past week or two, erythrocytes over the past month or two, and adipose tissue over a period of years. These findings may help in assessing the intake of (n- 3) fatty acids in epidemiological studies

Sex Difference in Chest Pain After Implantation of Newer Generation Coronary Drug-Eluting Stents: A Patient-Level Pooled Analysis From the TWENTE and DUTCH PEERS Trials

Item does not contain fulltextOBJECTIVES: This study sought to assess sex differences in chest pain after percutaneous coronary intervention (PCI) with newer generation drug-eluting stents (DES). BACKGROUND: Sex-based data on chest pain after PCI with DES are scarce. METHODS: The authors performed a patient-level pooled analysis of the TWENTE and DUTCH PEERS randomized trials, in which patients were treated with newer generation permanent polymer-coated DES. At 1 and 2 years, clinical follow-up was available in 99.8% and patient-reported chest pain data in 94.1% and 93.6%, respectively. RESULTS: Among all 3,202 patients, the 871 (27.2%) women were older (67.5 +/- 10.2 years vs. 62.8 +/- 10.6 years; p < 0.001) and had more cardiovascular risk factors: diabetes (24.2% vs. 17.8%; p < 0.001), hypertension (63.6% vs. 51.6%; p < 0.001), and positive family history (54.5% vs. 50.1%; p = 0.03). At 1- and 2-year follow-up, women reported more clinically relevant chest pain (16.3% vs. 10.5%; p < 0.001, and 17.2% vs. 11.1%; p < 0.001, respectively). Multivariate analysis demonstrated that female sex independently predicted clinically relevant chest pain at 1- and 2-year follow-up both during daily activities and at minimum physical exertion/at rest (1 year adjusted odds ratio [OR]: 1.7; 95% confidence interval [CI]: 1.2 to 2.4; p = 0.002; and adjusted OR: 1.8; 95% CI: 1.3 to 2.5; p < 0.001; 2-year adjusted OR: 1.8; 95% CI: 1.3 to 2.6; p < 0.001; and adjusted OR: 1.7; 95% CI: 1.3 to 2.3; p = 0.001). Nevertheless, the 2-year rates of death, myocardial infarction, revascularization, stent thrombosis, and various composite clinical endpoints were similar for both sexes. CONCLUSIONS: Although the incidence of adverse cardiovascular events was low and similar for both sexes, women showed a statistically significantly higher prevalence of clinically relevant chest pain, which might be largely related to mechanisms other than epicardial coronary obstruction

Clinical outcome following second-generation drug-eluting stent use for off-label versus on-label indications: Insights from the two-year outcome of the TWENTE trial

Aims: Drug-eluting stents (DES) were first used on-label - in simple patients with low clinical risk and easily accessible lesions. Currently, DES are increasingly used off-label - in complex patients undergoing percutaneous coronary interventions (PCI) with historically higher event risk. Therefore, our aim was to investigate whether patients with off-label indications for DES use had similar outcomes compared to patients who were treated for on-label indications only. Methods and results: We analysed two-year follow-up data of 1,387 TWENTE trial patients, treated with second-generation everolimus-eluting XIENCE V or zotarolimus-eluting Resolute stents, and compared off-label vs. on-label DES use with regard to the following clinical endpoints: cardiac death, myocardial infarction (MI), periprocedural MI (≤48 hrs), and target vessel revascularisation (TVR). Patients with off-label DES use (n=1,033; 74.5-) had more diabetes (22.9- vs. 17.5-; p=0.032), previous MI (35.9- vs. 22.3-; p0.8). Following off-label DES use, there was a higher incidence of PMI (5.0- vs. 1.4-; p=0.003), of which only 1.1- reached creatine kinase levels >5x the upper limit of normal (ULN). Conclusions: Despite differences in risk profile, patients with off-label DES use did not differ from patients with on-label DES use in clinical endpoints other than periprocedural MI. These largely positive findings underline the favourable safety profile of second-generation DES