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Sample records for everolimus eluting coronary

  1. A prospective, randomized evaluation of a novel everolimus-eluting coronary stent

    DEFF Research Database (Denmark)

    Stone, Gregg W; Teirstein, Paul S; Meredith, Ian T

    2011-01-01

    We sought to evaluate the clinical outcomes with a novel platinum chromium everolimus-eluting stent (PtCr-EES) compared with a predicate cobalt chromium everolimus-eluting stent (CoCr-EES) in patients undergoing percutaneous coronary intervention (PCI).......We sought to evaluate the clinical outcomes with a novel platinum chromium everolimus-eluting stent (PtCr-EES) compared with a predicate cobalt chromium everolimus-eluting stent (CoCr-EES) in patients undergoing percutaneous coronary intervention (PCI)....

  2. Comparison of zotarolimus-eluting and everolimus-eluting coronary stents

    DEFF Research Database (Denmark)

    Serruys, Patrick W; Silber, Sigmund; Garg, Scot

    2010-01-01

    New-generation coronary stents that release zotarolimus or everolimus have been shown to reduce the risk of restenosis. However, it is unclear whether there are differences in efficacy and safety between the two types of stents on the basis of prospectively adjudicated end points endorsed...

  3. XIENCE V everolimus-eluting coronary stent system: a novel second generation drug-eluting stent

    NARCIS (Netherlands)

    Beijk, Marcel A. M.; Piek, Jon J.

    2007-01-01

    Drug-eluting stents (DES) have been shown to be safe and significantly reduce clinical events and angiographic restenosis in the percutaneous treatment of coronary artery disease. Currently, three DES have been approved in Europe and Northern America: the sirolimus-eluting stent (SES), the

  4. Comparison of an everolimus-eluting bioresorbable scaffold with an everolimus-eluting metallic stent for the treatment of coronary artery stenosis (ABSORB II)

    DEFF Research Database (Denmark)

    Serruys, Patrick W; Chevalier, Bernard; Sotomi, Yohei

    2016-01-01

    BACKGROUND: No medium-term data are available on the random comparison between everolimus-eluting bioresorbable vascular scaffolds and everolimus-eluting metallic stents. The study aims to demonstrate two mechanistic properties of the bioresorbable scaffold: increase in luminal dimensions as a re...

  5. Comparison of in vivo acute stent recoil between the bioabsorbable everolimus-eluting coronary stent and the everolimus-eluting cobalt chromium coronary stent: insights from the ABSORB and SPIRIT trials

    DEFF Research Database (Denmark)

    Tanimoto, Shuzou; Serruys, Patrick W; Thuesen, Leif

    2007-01-01

    OBJECTIVES: This study sought to evaluate and compare in vivo acute stent recoil of a novel bioabsorbable stent and a metallic stent. BACKGROUND: The bioabsorbable everolimus-eluting coronary stent (BVS) is composed of a poly-L-lactic acid backbone, coated with a bioabsorbable polymer containing...... the antiproliferative drug, everolimus, and expected to be totally metabolized and absorbed in the human body. Because the BVS is made from polymer, it may have more acute recoil than metallic stents in vivo. METHODS: A total of 54 patients, who underwent elective stent implantation for single de novo native coronary...... artery lesions, were enrolled: 27 patients treated with the BVS and 27 patients treated with the everolimus-eluting cobalt chromium stent (EES). Acute absolute recoil, assessed by quantitative coronary angiography, was defined as the difference between mean diameter of the last inflated balloon...

  6. Comparison of everolimus- and paclitaxel-eluting stents in patients with acute and stable coronary syndromes: pooled results from the SPIRIT (A Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System) and COMPARE (A Trial of Everolimus-Eluting Stents and Paclitaxel-Eluting Stents for Coronary Revascularization in Daily Practice) Trials.

    Science.gov (United States)

    Planer, David; Smits, Pieter C; Kereiakes, Dean J; Kedhi, Elvin; Fahy, Martin; Xu, Ke; Serruys, Patrick W; Stone, Gregg W

    2011-10-01

    This study sought to compare the clinical outcomes of everolimus-eluting stents (EES) versus paclitaxel-eluting stents (PES) in patients with acute coronary syndromes (ACS) and stable coronary artery disease (CAD). Although randomized trials have shown superiority of EES to PES, the safety and efficacy of EES in ACS is unknown. We performed a patient-level pooled analysis from the prospective, randomized SPIRIT (Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System) II, III, IV, and COMPARE (A Trial of Everolimus-Eluting Stents and Paclitaxel-Eluting Stents for Coronary Revascularization in Daily Practice) trials in which 2,381 patients with ACS and 4,404 patients with stable CAD were randomized to EES or to PES. Kaplan-Meier estimates of death, myocardial infarction (MI), ischemia-driven target lesion revascularization, and stent thrombosis were assessed at 2 years and stratified by clinical presentation (ACS vs. stable CAD). At 2 years, patients with ACS compared with stable CAD had higher rates of death (3.2% vs. 2.4%, hazard ratio [HR]: 1.37 [95% confidence interval (CI): 1.02 to 1.85], p = 0.04) and MI (4.9% vs. 3.4%, HR: 1.45 [95% CI: 1.14 to 1.85], p = 0.02). In patients with ACS, EES versus PES reduced the rate of death or MI (6.6% vs. 9.3%, HR: 0.70 [95% CI: 0.52 to 0.94], p = 0.02), stent thrombosis (0.7% vs. 2.9%, HR: 0.25 [95% CI: 0.12 to 0.52], p = 0.0002), and ischemia-driven target lesion revascularization (4.7% vs. 6.2%, HR: 0.69 [95% CI: 0.48 to 0.99], p = 0.04). In patients with stable CAD, EES reduced the rate of death or MI (4.5% vs. 7.1%, HR: 0.62 [95% CI: 0.48 to 0.80], p = 0.0002), stent thrombosis (0.7% vs. 1.8%, HR: 0.34 [95% CI: 0.19 to 0.62], p = 0.0002), and ischemia-driven target lesion revascularization (3.9% vs. 6.9%, HR: 0.55 [95% CI: 0.42 to 0.73], p SPIRIT II]; NCT00180310; SPIRIT III: A Clinical Evaluation of the Investigational Device XIENCE V Everolimus Eluting Coronary Stent System [EECSS] in the

  7. Randomised comparison of a bioresorbable everolimus-eluting scaffold with a metallic everolimus-eluting stent for ischaemic heart disease caused by de novo native coronary artery lesions

    DEFF Research Database (Denmark)

    Chevalier, Bernard; Onuma, Yoshinobu; van Boven, Ad J

    2016-01-01

    AIMS: The one-year randomised data of the ABSORB II trial showed that the everolimus-eluting bioresorbable scaffold and the everolimus-eluting metallic stent were comparable for the composite secondary clinical outcomes of patient-oriented composite endpoint (PoCE) and device-oriented composite...... Clara, CA, USA) or treatment with an everolimus-eluting metallic stent (XIENCE; Abbott Vascular). The trial enrolled 501 patients. Clinical follow-up at two years was available in 320 patients in the Absorb BVS arm and 160 patients in the XIENCE arm. At two years, the PoCE for the Absorb and XIENCE arms......-six percent and 34% of patients remained on DAPT at two years, respectively. Ninety-two percent of patients in both arms remained on aspirin. CONCLUSIONS: Two-year clinical results demonstrate sustained low rates of PoCE, MACE, DoCE and TVF with the Absorb BVS as compared to the XIENCE stent....

  8. Rationale and Design of a Randomized Clinical Comparison of Everolimus-Eluting (Xience V/Promus) and Sirolimus-Eluting (Cypher Select+) Coronary Stents in Unselected Patients with Coronary Heart Disease

    DEFF Research Database (Denmark)

    Jensen, Lisette Okkels; Thayssen, Per; Tilsted, Hans Henrik

    2010-01-01

    with Clinical Outcome (SORT OUT) IV trial was designed as a prospective, multi-center, open-label, all-comer, two-arm, randomized, non-inferiority study comparing the everolimus-eluting stent with the sirolimus-eluting stent in the treatment of atherosclerotic coronary artery lesions. Based on a non...

  9. A randomised comparison of an everolimus-eluting coronary stent with a paclitaxel-eluting coronary stent:the SPIRIT II trial

    NARCIS (Netherlands)

    Serruys, Patrick W.; Ruygrok, Peter; Neuzner, Jörg; Piek, Jan J.; Seth, Ashok; Schofer, Joachim J.; Richardt, Gert; Wiemer, Marcus; Carrié, Didier; Thuesen, Leif; Boone, Els; Miquel-Herbert, Karine; Daemen, Joost

    2006-01-01

    Background: Everolimus has been successfully tested in humans using both an erodable and a durable polymer in small previous studies.Methods: This single blind multi-centre non-inferiority randomised (3:1) controlled trial evaluated the safety and performance of the XIENCE V Everolimus Eluting

  10. A bioresorbable everolimus-eluting scaffold versus a metallic everolimus-eluting stent for ischaemic heart disease caused by de-novo native coronary artery lesions (ABSORB II): an interim 1-year analysis of clinical and procedural secondary outcomes from a randomised controlled trial

    NARCIS (Netherlands)

    Serruys, Patrick W.; Chevalier, Bernard; Dudek, Dariusz; Cequier, Angel; Carrié, Didier; Iniguez, Andres; Dominici, Marcello; van der Schaaf, René J.; Haude, Michael; Wasungu, Luc; Veldhof, Susan; Peng, Lei; Staehr, Peter; Grundeken, Maik J.; Ishibashi, Yuki; Garcia-Garcia, Hector M.; Onuma, Yoshinobu

    2015-01-01

    Despite rapid dissemination of an everolimus-eluting bioresorbable scaffold for treatment for coronary artery disease, no data from comparisons with its metallic stent counterpart are available. In a randomised controlled trial we aimed to compare an everolimus-eluting bioresorbable scaffold with an

  11. The SYNERGY biodegradable polymer everolimus eluting coronary stent: Porcine vascular compatibility and polymer safety study.

    Science.gov (United States)

    Wilson, Gregory J; Marks, Angela; Berg, Kimberly J; Eppihimer, Michael; Sushkova, Natalia; Hawley, Steve P; Robertson, Kimberly A; Knapp, David; Pennington, Douglas E; Chen, Yen-Lane; Foss, Aaron; Huibregtse, Barbara; Dawkins, Keith D

    2015-11-15

    SYNERGY is a novel platinum chromium alloy stent that delivers abluminal everolimus from an ultrathin poly-lactide-co-glycide (PLGA) biodegradable polymer. This study evaluated the in vivo degradation of the polymer coating, everolimus release time course, and vascular compatibility of the SYNERGY stent. SYNERGY stents were implanted in arteries of domestic swine. Devices were explanted at predetermined time points (up to 120 days) and the extent of PLGA coating or everolimus remaining on the stents was quantified. Everolimus levels in the arterial tissue were also evaluated. A pathological analysis on coronary arteries of single and overlapping stents was performed at time points between 5 and 270 days. PLGA bioabsorption began immediately after implantation, and drug release was essentially complete by 90 days; PLGA absorption was substantially complete by 120 days (>90% of polymer was absorbed) leaving a bare metal SYNERGY stent. Vascular response was similar among SYNERGY and control stents (bare metal, polymer-only, and 3× polymer-only). Mild increases in para-strut fibrin were seen for SYNERGY at an early time point with no significant differences in all other morphological and morphometric parameters through 270 days or endothelial function (eNOS immunostaining) at 90 or 180 days. Inflammation was predominantly minimal to mild for all device types. In a swine model, everolimus was released by 90 days and PLGA bioabsorption was complete shortly thereafter. The SYNERGY stent and its biodegradable polymer, even at a 3× safety margin, demonstrated vascular compatibility similar to bare metal stent controls. © 2015 Wiley Periodicals, Inc.

  12. An everolimus-eluting stent versus a paclitaxel-eluting stent in small vessel coronary artery disease: a pooled analysis from the SPIRIT II and SPIRIT III trials.

    Science.gov (United States)

    Bartorelli, Antonio L; Serruys, Patrick W; Miquel-Hébert, Karine; Yu, Shui; Pierson, Wes; Stone, Gregg W

    2010-07-01

    To evaluate the safety and efficacy of the XIENCE V everolimus-eluting stent compared to the TAXUS paclitaxel-eluting stent in small vessels. The XIENCE V everolimus-eluting stent (EES) has been shown to improve angiographic and clinical outcomes after percutaneous myocardial revascularization, but its performance in small coronary arteries has not been investigated. In this pooled analysis, we studied a cohort of 541 patients with small coronary vessels (reference diameter SPIRIT II and SPIRIT III studies. TAXUS Express (73% of lesions) and TAXUS Liberté (27% of lesions) paclitaxel-eluting stents (PES) were used as controls in SPIRIT II. In SPIRIT III, Taxus Express(2) PES was the control. Mean angiographic in-stent and in-segment late loss was significantly less in the EES group compared with the PES group, (0.15 +/- 0.37 mm vs. 0.30 +/- 0.44 mm; P = 0.011 for in-stent; 0.10 +/- 0.38 mm vs. 0.21 +/- 0.34 mm; P = 0.034 for in-segment). EES also resulted in a significant reduction in composite major adverse cardiac events at 1 year (19/366 [5.2%] vs. 17/159 [10.7%]; P = 0.037), due to fewer non-Q-wave myocardial infarctions and target lesion revascularizations. At 1 year, the rate of non-Q-wave myocardial infarction was significantly lower in the EES group compared with that of the PES group (6/366 [1.6%] vs. 8/159 [5.0%]; P = 0.037). In patients with small vessel coronary arteries, the XIENCE V EES was superior to the TAXUS PES. (c) 2010 Wiley-Liss, Inc.

  13. Comparison of an everolimus-eluting bioresorbable scaffold with an everolimus-eluting metallic stent for the treatment of coronary artery stenosis (ABSORB II): a 3 year, randomised, controlled, single-blind, multicentre clinical trial

    NARCIS (Netherlands)

    Serruys, Patrick W.; Chevalier, Bernard; Sotomi, Yohei; Cequier, Angel; Carrié, Didier; Piek, Jan J.; van Boven, Ad J.; Dominici, Marcello; Dudek, Dariusz; McClean, Dougal; Helqvist, Steffen; Haude, Michael; Reith, Sebastian; de Sousa Almeida, Manuel; Campo, Gianluca; Iñiguez, Andrés; Sabaté, Manel; Windecker, Stephan; Onuma, Yoshinobu

    2016-01-01

    No medium-term data are available on the random comparison between everolimus-eluting bioresorbable vascular scaffolds and everolimus-eluting metallic stents. The study aims to demonstrate two mechanistic properties of the bioresorbable scaffold: increase in luminal dimensions as a result of

  14. The SPIRIT V study: a clinical evaluation of the XIENCE V everolimus-eluting coronary stent system in the treatment of patients with de novo coronary artery lesions.

    Science.gov (United States)

    Grube, Eberhard; Chevalier, Bernard; Smits, Peter; Džavík, Vladimir; Patel, Tejas M; Mullasari, Ajit S; Wöhrle, Jochen; Stuteville, Marrianne; Dorange, Cécile; Kaul, Upendra

    2011-02-01

    The SPIRIT V (A Clinical Evaluation of the XIENCE V Everolimus-Eluting Coronary Stent System in the Treatment of Patients With De Novo Coronary Artery Lesions) study is a post-market surveillance experience of the XIENCE V (Abbott Vascular, Santa Clara, California) everolimus-eluting stent (EES) in patients with higher-risk coronary anatomy. Previous pre-approval studies have shown the safety and efficacy of EES in highly selected groups of patients. The SPIRIT V trial is a prospective, open label, single arm, multicenter study. Two thousand seven hundred patients with multiple de novo coronary artery lesions suitable for treatment with a planned maximum of 4 EES were enrolled at 93 centers in Europe, Asia Pacific, Canada, and South Africa. Lesions had a reference vessel diameter between 2.25 and 4.0 mm and a length of ≤ 28 mm by visual estimation. An independent clinical events committee adjudicated all end point-related events. The primary end point was the composite rate of all death, myocardial infarction (MI), and target vessel revascularization at 30 days. Secondary end points included stent thrombosis and acute success (clinical device and procedure success). At 30 days, the primary composite end point of all death, MI, and target vessel revascularization was 2.7%. At 1 year, rates of cardiac death, overall MI, and target lesion revascularization were 1.1%, 3.5%, and 1.8%, respectively. The cumulative rate of definite and probable stent thrombosis was low at 0.66% at 1 year. Use of EES in patients with multiple, complex de novo lesions yielded 1-year major adverse cardiac events, stent thrombosis, and target lesion revascularization rates that are comparable to those of the more controlled SPIRIT II and SPIRIT III trials-which included patients with restricted inclusion/exclusion criteria-and other all-comer population, physician-initiated studies like the X-SEARCH (Xience Stent Evaluated At Rotterdam Cardiology Hospital) and COMPARE (A Randomized

  15. Incidence and Potential Mechanism(s) of Post-Procedural Rise of Cardiac Biomarker in Patients With Coronary Artery Narrowing After Implantation of an Everolimus-Eluting Bioresorbable Vascular Scaffold or Everolimus-Eluting Metallic Stent

    DEFF Research Database (Denmark)

    Ishibashi, Yuki; Muramatsu, Takashi; Nakatani, Shimpei

    2015-01-01

    OBJECTIVES: This study sought to evaluate the mechanism of post-procedural cardiac biomarker (CB) rise following device implantation. BACKGROUND: A fully bioresorbable Absorb scaffold, compared with everolimus-eluting metallic stents (EES), might be associated with a higher incidence...

  16. Percutaneous coronary intervention with second-generation paclitaxel-eluting stents versus everolimus-eluting stents in United States contemporary practice (REWARDS TLX Trial).

    Science.gov (United States)

    Waksman, Ron; Ghali, Magdi; Goodroe, Randy; Ryan, Thomas; Turco, Mark; Ring, Michael; McGarry, Thomas; Dobies, David; Shammas, Nicolas; Steinberg, Daniel H; Swymelar, Stacy; Kaneshige, Kimberly; Torguson, Rebecca

    2012-10-15

    Registry Experience at the Washington Hospital Center, DES - Taxus Liberte Versus Xience V (REWARDS TLX) is a physician-initiated, retrospective, real-world, multicenter, observational study for all patients >18 years of age subjected to percutaneous coronary intervention with everolimus-eluting stents (EESs) or paclitaxel-eluting stents (PESs). Outcomes of patients receiving a TAXUS Liberté or XIENCE V drug-eluting stent were compared. Baseline clinical, procedural, and follow-up data at 12 months were collected from 10 clinical centers by an electronic data capture system. The study's primary end point was major adverse cardiac events: a composite of all-cause death, Q-wave myocardial infarction, target vessel revascularization, and stent thrombosis. The trial is registered with http://www.clinicaltrials.gov (NCT01134159). Data were entered for 1,195 patients (PES, n = 595; EES, n = 600). Baseline clinical characteristics were similar except for higher dyslipidemia, systemic hypertension, and family history of coronary artery disease in the EES group. In-hospital outcome was similar between groups, with an overall in-hospital stent thrombosis rate of 0.2%. The primary end point at 12 months was similar (EES 7.8% vs 10.8%, p = 0.082). Overall stent thrombosis rate was lower in the EES group (0.3% vs 1.2%, respectively, p = 0.107); however, target lesion revascularization was similar (PES, hazard ratio 1.46, 95% confidence interval 0.98 to 2.19, p = 0.064). There was no difference in overall mortality between groups. In conclusion, second-generation EESs and PESs demonstrated similar efficacy and safety profiles for broadened patient and lesion subsets compared to a selected population from the pivotal trials. However, for composite efficacy and safety end points, EESs outperformed second-generation PESs. Copyright © 2012 Elsevier Inc. All rights reserved.

  17. Safety and efficacy of everolimus-eluting stents compared with first-generation drug-eluting stents in patients undergoing primary percutaneous coronary intervention

    Energy Technology Data Exchange (ETDEWEB)

    Escárcega, Ricardo O.; Baker, Nevin C.; Magalhaes, Marco A.; Lipinski, Michael J.; Minha, Sa’ar; Torguson, Rebecca; Satler, Lowell F.; Pichard, Augusto D.; Suddath, William O.; Waksman, Ron, E-mail: ron.waksman@medstar.net

    2014-09-15

    Objective: To assess the safety and efficacy everolimus-eluting stents (EES) compared with first-generation drug-eluting stents (DES) in patients with acute myocardial infarction (MI) undergoing primary percutaneous coronary intervention (PCI). Background: EES have been associated with improved clinical outcomes compared to paclitaxel-eluting stents (PES) and with similar outcomes compared to sirolimus-eluting stents (SES). Methods: A total of 520 patients who presented with ST-elevation myocardial infarction (STEMI) from 2003 to 2013, who underwent primary PCI with DES, were retrospectively analyzed. Of these, 247 received SES, 136 PES, and 137 EES. Patients were followed up to 2 years for major adverse cardiac events (MACE). Univariate and multivariate models detected correlates to outcome. Results: EES implantation, compared with PES and SES, resulted in comparable rates of MACE (8.8% vs. 16.2%, p = 0.06 and 8.8% vs. 12.6%, respectively, p = 0.26), stent thrombosis, MI, and target lesion revascularization. Patients who received EES had lower rates of all-cause mortality (3.7% vs. 12.6% vs. 9.4%, p = 0.03) at 1-year follow up. However, in the univariate and multivariate analyses, stent type was not independently associated with the primary outcome or with all-cause mortality. Diabetes mellitus and number of stents implanted were independently associated with the primary outcome. Conclusion: While EES seem to be associated with better outcome when compared to PES, the main correlates of STEMI patients are the presence of diabetes and number of stents implanted, and not the type of stent used for intervention.

  18. Effect of Post-Dilatation Following Primary PCI With Everolimus-Eluting Bioresorbable Scaffold Versus Everolimus-Eluting Metallic Stent Implantation

    DEFF Research Database (Denmark)

    Yamaji, Kyohei; Brugaletta, Salvatore; Sabaté, Manel

    2017-01-01

    OBJECTIVES: This study sought to investigate the effect of post-dilatation on angiographic and intracoronary imaging parameters in the setting of primary percutaneous coronary intervention comparing the everolimus-eluting bioresorbable scaffold (BRS) with the everolimus-eluting metallic stent (EE...

  19. Zotarolimus-eluting Resolute Integrity versus everolimus-eluting Xience Xpedition stents in the management of very long (>30 mm) de novo coronary artery stenosis

    Energy Technology Data Exchange (ETDEWEB)

    Patra, Soumya, E-mail: dr_soumyapatra@rediffmail.com; Chakraborty, Rabindra Nath; Pande, Arindam; Banerjee, Suvro; Jena, Manabhanjan; Mandal, Prakash Chandra; De, Swapan Kumar; Khan, Aftab; Das, Sankha Suvro; Ghosh, Debashish; Nag, Raja

    2017-04-15

    Background: Procedural and clinical outcomes in patients with very long (>30 mm) coronary lesions who underwent stent-based percutaneous coronary interventions are still unfavorable. Therefore, we compared the relative efficacy and safety of resolute zotarolimus-eluting stents (R-ZES) and Xpedition everolimus-eluting stents (X-EES) for patients with de novo very long coronary lesions. Methods: This comparative single-centre, retrospective study compared long R-ZES and X-EES in consecutive patients admitted with very long (≥30 mm) native ACC/AHA type C coronary lesions in 2014. All patients were followed up clinically at 1, 3, 6 and 12 months. In this study, only symptom-driven angiogram was advised. The study end point was to evaluate immediate procedural success and one-year rate of target lesion failure (TLF), which is a composite of cardiac death, target lesion myocardial infarction, or target lesion revascularization (TLR). Results: Total number of patients enrolled in this study was 185 (R-ZES = 107; X-EES = 78). The baseline characteristics and post procedural success rate were similar between R-ZES and X-EES groups, including the post stenting lesion lengths (36.6 ± 1.92 mm vs 40.71 ± 6.175 mm, P = 0.09). At 12-month follow-up, there were no significant between-group differences in the rate of adverse clinical events (death, myocardial infarction, stent thrombosis, target lesion revascularization, and composite outcomes). Procedural success was achieved in 94% in R-ZES group and 93% in X-EES group (P = 0.24). The incidence of TLF was 5% in R-ZES and 4% in X-EES groups (HR-1.25; 95% CI-0.86-5.6; P = 0.19). Conclusion: Patients with de novo long coronary artery disease, R-ZES implantation showed similar clinical outcome as compared with X-EES implantation. - Highlights: • This is the first study comparing between R-ZES (Resolute Integrity) and X-EES (Xience Xpedition) used in PCI for long coronary artery disease. Here, single stent length of more than 30

  20. Paclitaxel-eluting stents versus everolimus-eluting coronary stents in a diabetic population: two-year follow-up of the TUXEDO-India trial.

    Science.gov (United States)

    Kaul, Upendra; Bhagwat, Ajit; Pinto, Brian; Goel, Praveen K; Jagtap, Prashant; Sathe, Shireesh; Wander, Gurpreet S; Arambam, Priyadarshini; Bangalore, Sripal

    2017-11-20

    The aim of this study was to report whether the superiority of the everolimus-eluting stent (EES) vs. the paclitaxel-eluting stent (PES) at one-year follow-up in the Taxus Element versus Xience Prime in a Diabetic Population (TUXEDO)-India trial was sustained at longer-term follow-up. One thousand eight hundred and thirty (1,830) patients with diabetes mellitus and coronary artery disease were randomised to EES vs. PES. Follow-up data up to two years were available in 1,701 (92.9%) patients. The primary endpoint was target vessel failure (TVF), defined as the composite of cardiac death, target vessel myocardial infarction (TV-MI), or ischaemia-driven target vessel revascularisation (TVR). Treatment with EES had a lower two-year rate of TVF (4.3% vs. 6.6%, p=0.03). Of the secondary endpoints, EES significantly reduced any MI (1.6% vs. 3.5%, p=0.01), TV-MI (0.7% vs. 3.1%, p=0.0001), ST (0.4% vs. 2.2%, p=0.001), cardiac death or target vessel MI (2.9% vs. 4.8%, p=0.04) and TLR (1.9% vs. 3.7%, p=0.02), compared with PES. Between one year and two years, no significant differences in the clinical outcomes were observed (pinteraction >0.05). In this adequately powered trial, the benefits of EES vs. PES in a diabetic population seen at one year were maintained at two years.

  1. Comparative vascular responses three months after paclitaxel and everolimus-eluting stent implantation in streptozotocin-induced diabetic porcine coronary arteries

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    Sheehy Alexander

    2012-06-01

    Full Text Available Abstract Background Diabetes remains a significant risk factor for restenosis/thrombosis following stenting. Although vascular healing responses following drug-eluting stent (DES treatment have been characterized previously in healthy animals, comparative assessments of different DES in a large animal model with isolated features of diabetes remains limited. We aimed to comparatively assess the vascular response to paclitaxel-eluting (PES and everolimus-eluting (EES stents in a porcine coronary model of streptozotocin (STZ-induced type I diabetes. Method Twelve Yucatan swine were induced hyperglycemic with a single STZ dose intravenously to ablate pancreatic β-cells. After two months, each animal received one XIENCE V® (EES and one Taxus Liberte (PES stent, respectively, in each coronary artery. After three months, vascular healing was assessed by angiography and histomorphometry. Comparative in vitro effects of everolimus and paclitaxel (10-5 M–10-12 M after 24 hours on carotid endothelial (EC and smooth muscle (SMC cell viability under hyperglycemic (42 mM conditions were assayed by ELISA. Caspase-3 fluorescent assay was used to quantify caspase-3 activity of EC treated with everolimus or paclitaxel (10-5 M, 10-7 M for 24 hours. Results After 3 months, EES reduced neointimal area (1.60 ± 0.41 mm, p vs. 0.08 ± 0.05, greater medial necrosis grade (0.52 ± 0.26 vs. 0.0 ± 0.0, and persistently elevated fibrin scores (1.60 ± 0.60 vs. 0.63 ± 0.41 with PES compared to EES (p In vitro, paclitaxel significantly increased (p -7 M, while everolimus did not affect EC/SMC apoptosis/necrosis within the dose range tested. In ECs, paclitaxel (10-5 M significantly increased caspase-3 activity (p  Conclusion After 3 months, both DES exhibited signs of delayed healing in a STZ-induced diabetic swine model. PES exhibited greater neointimal area, increased inflammation, greater medial necrosis, and

  2. Long-Term Follow-Up of Patients after Percutaneous Coronary Intervention with Everolimus-Eluting Bioresorbable Vascular Scaffold.

    Science.gov (United States)

    Meneguz-Moreno, Rafael Alexandre; Costa, José de Ribamar; Moscoso, Freddy Antônio Britto; Staico, Rodolfo; Tanajura, Luiz Fernando Leite; Centemero, Marinella Patrizia; Chaves, Auréa Jacob; Abizaid, Andrea Claudia Leão de Sousa; Sousa, Amanda Guerra de Moraes Rego E; Abizaid, Alexandre Antonio Cunha

    2017-02-01

    Bioresorbable vascular scaffolds (BVS) were developed to improve the long-term results of percutaneous coronary intervention, restoring vasomotion. To report very late follow-up of everolimus-eluting Absorb BVS (Abbott Vascular, Santa Clara, USA) in our center. Observational retrospective study, in a single Brazilian center, from August 2011 to October 2013, including 49 patients submitted to Absorb BVS implantation. Safety and efficacy outcomes were analyzed in the in-hospital and very late follow-up phases (> 2 years). All 49 patients underwent a minimum follow-up of 2.5 years and a maximum of 4.6 years. Mean age was 56.8 ± 7.6 years, 71.4% of the patients were men, and 26.5% were diabetic. Regarding clinical presentation, the majority (94%) had stable angina or silent ischemia. Device success was achieved in 100% of cases with 96% overall procedure success rate. Major adverse cardiovascular events rate was 4% at 30 days, 8.2% at 1 year, and 12.2% at 2 years, and there were no more events until 4.6 years. There were 2 cases of thrombosis (1 subacute and 1 late). In this preliminary analysis, Absorb BVS showed to be a safe and effective device in the very late follow-up. Establishing the efficacy and safety profiles of these devices in more complex scenarios is necessary. Os suportes vasculares bioabsorvíveis (SVB) foram desenvolvidos com o intuito de melhorar os resultados da intervenção coronária percutânea a longo prazo, restabelecendo-se a vasomotricidade. Reportar o seguimento muito tardio do implante do SVB eluidor de everolimus Absorb® (Abbot Vascular, Santa Clara, EUA) em nosso centro. Estudo observacional, retrospectivo, em um único centro brasileiro, que incluiu 49 pacientes submetidos ao implante do SVB Absorb® entre agosto/2011 e outubro/2013. Foram analisados os desfechos de segurança e eficácia na fase hospitalar e bastante tardia (> 2 anos). Todos os 49 pacientes completaram um seguimento mínimo de 2,5 anos, sendo o máximo de 4,6 anos

  3. Biodegradable Polymer Biolimus-Eluting Stents Versus Durable Polymer Everolimus-Eluting Stents in Patients With Coronary Artery Disease: Final 5-Year Report From the COMPARE II Trial (Abluminal Biodegradable Polymer Biolimus-Eluting Stent Versus Durable Polymer Everolimus-Eluting Stent).

    Science.gov (United States)

    Vlachojannis, Georgios J; Smits, Pieter C; Hofma, Sjoerd H; Togni, Mario; Vázquez, Nicolás; Valdés, Mariano; Voudris, Vassilis; Slagboom, Ton; Goy, Jean-Jaques; den Heijer, Peter; van der Ent, Martin

    2017-06-26

    This analysis investigates the 5-year outcomes of the biodegradable polymer biolimus-eluting stent (BP-BES) and durable polymer everolimus-eluting stent (DP-EES) in an all-comers population undergoing percutaneous coronary intervention. Recent 1- and 3-year results from randomized trials have indicated similar safety and efficacy outcomes of BP-BES and DP-EES. Whether benefits of the biodegradable polymer device arise over longer follow-up is unknown. Moreover, in-depth, prospective, long-term follow-up data on metallic drug-eluting stents with durable or biodegradable polymers are scarce. The COMPARE II trial (Abluminal Biodegradable Polymer Biolimus-Eluting Stent Versus Durable Polymer Everolimus-Eluting Stent) was a prospective, randomized, multicenter, all-comers trial in which 2,707 patients were randomly allocated (2:1) to BP-BES or DP-EES. The pre-specified endpoint at 5 years was major adverse cardiac events, a composite of cardiac death, nonfatal myocardial infarction, or target vessel revascularization. Five-year follow-up was available in 2,657 patients (98%). At 5 years, major adverse cardiac events occurred in 310 patients (17.3%) in the BP-BES group and 142 patients (15.6%) in the DP-EES group (p = 0.26). The rate of the combined safety endpoint all-cause death or myocardial infarction was 15.0% in the BP-BES group versus 14.8% in the DP-EES group (p = 0.90), whereas the efficacy measure target vessel revascularization was 10.6% versus 9.0% (p = 0.18), respectively. Interestingly, definite stent thrombosis rates did not differ between groups (1.5% for BP-BES vs. 0.9% for DP-EES; p = 0.17). The 5-year analysis comparing biodegradable polymer-coated BES and the durable polymer-coated EES confirms the initial early- and mid-term results regarding similar safety and efficacy outcomes in this all-comers percutaneous coronary intervention population. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights

  4. The prognostic utility of the SYNTAX score on 1-year outcomes after revascularization with zotarolimus- and everolimus-eluting stents: a substudy of the RESOLUTE All Comers Trial

    DEFF Research Database (Denmark)

    Garg, Scot; Serruys, Patrick W; Silber, Sigmund

    2011-01-01

    This study assessed the ability of the SYNTAX score (SXscore) to stratify risk in patients treated with percutaneous coronary intervention (PCI) using zotarolimus-eluting or everolimus-eluting stents.......This study assessed the ability of the SYNTAX score (SXscore) to stratify risk in patients treated with percutaneous coronary intervention (PCI) using zotarolimus-eluting or everolimus-eluting stents....

  5. A randomized multicenter comparison of hybrid sirolimus-eluting stents with bioresorbable polymer versus everolimus-eluting stents with durable polymer in total coronary occlusion: rationale and design of the Primary Stenting of Occluded Native Coronary Arteries IV study

    Directory of Open Access Journals (Sweden)

    Teeuwen Koen

    2012-12-01

    Full Text Available Abstract Background Percutaneous recanalization of total coronary occlusion (TCO was historically hampered by high rates of restenosis and reocclusions. The PRISON II trial demonstrated a significant restenosis reduction in patients treated with sirolimus-eluting stents compared with bare metal stents for TCO. Similar reductions in restenosis were observed with the second-generation zotarolimus-eluting stent and everolimus-eluting stent. Despite favorable anti-restenotic efficacy, safety concerns evolved after identifying an increased rate of very late stent thrombosis (VLST with drug-eluting stents (DES for the treatment of TCO. Late malapposition caused by hypersensitivity reactions and chronic inflammation was suggested as a probable cause of these VLST. New DES with bioresorbable polymer coatings were developed to address these safety concerns. No randomized trials have evaluated the efficacy and safety of the new-generation DES with bioresorbable polymers in patients treated for TCO. Methods/Design The prospective, randomized, single-blinded, multicenter, non-inferiority PRISON IV trial was designed to evaluate the safety, efficacy, and angiographic outcome of hybrid sirolimus-eluting stents with bioresorbable polymers (Orsiro; Biotronik, Berlin, Germany compared with everolimus-eluting stents with durable polymers (Xience Prime/Xpedition; Abbott Vascular, Santa Clara, CA, USA in patients with successfully recanalized TCOs. In total, 330 patients have been randomly allocated to each treatment arm. Patients are eligible with estimated duration of TCO ≥4 weeks with evidence of ischemia in the supply area of the TCO. The primary endpoint is in-segment late luminal loss at 9-month follow-up angiography. Secondary angiographic endpoints include in-stent late luminal loss, minimal luminal diameter, percentage of diameter stenosis, in-stent and in-segment binary restenosis and reocclusions at 9-month follow-up. Additionally, optical coherence

  6. The REMEDEE-OCT Study: An Evaluation of the Bioengineered COMBO Dual-Therapy CD34 Antibody-Covered Sirolimus-Eluting Coronary Stent Compared With a Cobalt-Chromium Everolimus-Eluting Stent in Patients With Acute Coronary Syndromes: Insights From Optical Coherence Tomography Imaging Analysis

    NARCIS (Netherlands)

    Jaguszewski, Milosz; Aloysius, Romila; Wang, Wei; Bezerra, Hiram G.; Hill, Jonathan; de Winter, Robbert J.; Karjalainen, Pasi P.; Verheye, Stefan; Wijns, William; Lüscher, Thomas F.; Joner, Michael; Costa, Marco; Landmesser, Ulf

    2017-01-01

    The aim of the present study was to evaluate vascular healing of the bioengineered COMBO Dual Therapy Stent compared with a cobalt-chromium (CoCr) everolimus-eluting stent (EES) as assessed by optical coherence tomography in patients with acute coronary syndromes. CD34+ cells promote endothelial

  7. Five-year clinical and functional multislice computed tomography angiographic results after coronary implantation of the fully resorbable polymeric everolimus-eluting scaffold in patients with de novo coronary artery disease: the ABSORB cohort A trial.

    Science.gov (United States)

    Onuma, Yoshinobu; Dudek, Dariusz; Thuesen, Leif; Webster, Mark; Nieman, Koen; Garcia-Garcia, Hector M; Ormiston, John A; Serruys, Patrick W

    2013-10-01

    This study sought to demonstrate the 5-year clinical and functional multislice computed tomography angiographic results after implantation of the fully resorbable everolimus-eluting scaffold (Absorb BVS, Abbott Vascular, Santa Clara, California). Multimodality imaging of the first-in-humans trial using a ABSORB BVS scaffold demonstrated at 2 years the bioresorption of the device while preventing restenosis. However, the long-term safety and efficacy of this therapy remain to be documented. In the ABSORB cohort A trial (ABSORB Clinical Investigation, Cohort A [ABSORB A] Everolimus-Eluting Coronary Stent System Clinical Investigation), 30 patients with a single de novo coronary artery lesion were treated with the fully resorbable everolimus-eluting Absorb scaffold at 4 centers. As an optional investigation in 3 of the 4 centers, the patients underwent multislice computed tomography (MSCT) angiography at 18 months and 5 years. Acquired MSCT data were analyzed at an independent core laboratory (Cardialysis, Rotterdam, the Netherlands) for quantitative analysis of lumen dimensions and was further processed for calculation of fractional flow reserve (FFR) at another independent core laboratory (Heart Flow, Redwood City, California). Five-year clinical follow-up is available for 29 patients. One patient withdrew consent after 6 months, but the vital status of this patient remains available. At 46 days, 1 patient experienced a single episode of chest pain and underwent a target lesion revascularization with a slight troponin increase after the procedure. At 5 years, the ischemia-driven major adverse cardiac event rate of 3.4% remained unchanged. Clopidogrel was discontinued in all but 1 patient. Scaffold thrombosis was not observed in any patient. Two noncardiac deaths were reported, 1 caused by duodenal perforation and the other from Hodgkin's disease. At 5 years, 18 patients underwent MSCT angiography. All scaffolds were patent, with a median minimal lumen area of 3

  8. Percutaneous Coronary Intervention of Left Main Disease: Pre- and Post-EXCEL (Evaluation of XIENCE Everolimus Eluting Stent Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) and NOBLE (Nordic-Baltic-British Left Main Revascularization Study) Era.

    Science.gov (United States)

    Park, Duk-Woo; Park, Seung-Jung

    2017-06-01

    For nearly half a century, coronary artery bypass grafting has been the standard treatment for patients with obstructive left main coronary artery (LMCA) disease. However, there has been considerable evolution in the field of percutaneous coronary intervention, and especially, percutaneous coronary intervention for LMCA disease has been rapidly expanded with adoption of drug-eluting stents. Some, but not all randomized trials, have shown that percutaneous coronary intervention with drug-eluting stents might be a suitable alternative for selected patients with LMCA disease instead of bypass surgery. However, none of previous trials involving early-generation drug-eluting stents was sufficiently powered and comparative trials using contemporary drug-eluting stents were limited. Recently, primary results of 2 new trials of EXCEL (Evaluation of XIENCE Everolimus Eluting Stent Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) and NOBLE (Nordic-Baltic-British Left Main Revascularization Study) were reported. However, these trials showed conflicting results, which might pose uncertainty on the optimal revascularization strategy for LMCA disease. In this article, with the incorporation of a key review on evolution of LMCA treatment, we summarize the similarity or disparity of the EXCEL and NOBLE trials, focus on how they relate to previous trials in the field, and finally speculate on how the treatment strategy may be changed or recommended for LMCA treatment. © 2017 American Heart Association, Inc.

  9. Evaluation of chemical stability of polymers of XIENCE everolimus-eluting coronary stents in vivo by pyrolysis-gas chromatography/mass spectrometry.

    Science.gov (United States)

    Kamberi, Marika; Pinson, David; Pacetti, Stephen; Perkins, Laura E L; Hossainy, Syed; Mori, Hiroyoshi; Rapoza, Richard J; Kolodgie, Frank; Virmani, Renu

    2017-09-07

    The polymers poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) and poly(n-butyl methacrylate) (PBMA) are employed in manufacturing the XIENCE family of coronary stents. PBMA serves as a primer and adheres to both the stent and the drug coating. PVDF-HFP is employed in the drug matrix layer to hold the drug everolimus on the stent and control its release. Chemical stability of the polymers of XIENCE stents in the in-vivo environment was evaluated by pyrolysis-gas chromatography with mass spectrometry (Py-GC/MS) detection. For this evaluation, XIENCE stents explanted from porcine coronary arteries and from human coronary artery specimens at autopsy after 2-4 and 5-7 years of implantation, respectively, were compared to freshly manufactured XIENCE stents (controls). The comparison of pyrograms of explanted stent samples and controls showed identical fragmentation fingerprints of polymers, indicating that PVDF-HFP and PBMA maintained their chemical integrity after multiple years of XIENCE coronary stent implantation. The findings of the present study demonstrate the chemical stability of PVDF-HFP and PBMA polymers of the XIENCE family of coronary stents in the in-vivo environment, and constitute a further proof of the suitability of PVDF-HFP as a drug carrier for the drug eluting stent applications. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2017. © 2017 Wiley Periodicals, Inc.

  10. A sirolimus-eluting bioabsorbable polymer-coated stent (MiStent) versus an everolimus-eluting durable polymer stent (Xience) after percutaneous coronary intervention (DESSOLVE III): a randomised, single-blind, multicentre, non-inferiority, phase 3 trial.

    Science.gov (United States)

    de Winter, Robbert J; Katagiri, Yuki; Asano, Taku; Milewski, Krzysztof P; Lurz, Philipp; Buszman, Pawel; Jessurun, Gillian A J; Koch, Karel T; Troquay, Roland P T; Hamer, Bas J B; Ophuis, Ton Oude; Wöhrle, Jochen; Wyderka, Rafał; Cayla, Guillaume; Hofma, Sjoerd H; Levesque, Sébastien; Żurakowski, Aleksander; Fischer, Dieter; Kośmider, Maciej; Goube, Pascal; Arkenbout, E Karin; Noutsias, Michel; Ferrari, Markus W; Onuma, Yoshinobu; Wijns, William; Serruys, Patrick W

    2018-02-03

    MiStent is a drug-eluting stent with a fully absorbable polymer coating containing and embedding a microcrystalline form of sirolimus into the vessel wall. It was developed to overcome the limitation of current durable polymer drug-eluting stents eluting amorphous sirolimus. The clinical effect of MiStent sirolimus-eluting stent compared with a durable polymer drug-eluting stents has not been investigated in a large randomised trial in an all-comer population. We did a randomised, single-blind, multicentre, phase 3 study (DESSOLVE III) at 20 hospitals in Germany, France, Netherlands, and Poland. Eligible participants were any patients aged at least 18 years who underwent percutaneous coronary intervention in a lesion and had a reference vessel diameter of 2·50-3·75 mm. We randomly assigned patients (1:1) to implantation of either a sirolimus-eluting bioresorbable polymer stent (MiStent) or an everolimus-eluting durable polymer stent (Xience). Randomisation was done by local investigators via web-based software with random blocks according to centre. The primary endpoint was a non-inferiority comparison of a device-oriented composite endpoint (DOCE)-cardiac death, target-vessel myocardial infarction, or clinically indicated target lesion revascularisation-between the groups at 12 months after the procedure assessed by intention-to-treat. A margin of 4·0% was defined for non-inferiority of the MiStent group compared with the Xience group. All participants were included in the safety analyses. This trial is registered with ClinicalTrials.gov, number NCT02385279. Between March 20, and Dec 3, 2015, we randomly assigned 1398 patients with 2030 lesions; 703 patients with 1037 lesions were assigned to MiStent, of whom 697 received the index procedure, and 695 patients with 993 lesions were asssigned to Xience, of whom 690 received the index procedure. At 12 months, the primary endpoint had occurred in 40 patients (5·8%) in the sirolimus-eluting stent group and in 45

  11. Biodegradable polymer sirolimus-eluting stents versus durable polymer everolimus-eluting stents for primary percutaneous coronary revascularisation of acute myocardial infarction.

    Science.gov (United States)

    Pilgrim, Thomas; Piccolo, Raffaele; Heg, Dik; Roffi, Marco; Tüller, David; Vuilliomenet, André; Muller, Olivier; Cook, Stéphane; Weilenmann, Daniel; Kaiser, Christoph; Jamshidi, Peiman; Khattab, Ahmed A; Taniwaki, Masanori; Rigamonti, Fabio; Nietlispach, Fabian; Blöchlinger, Stefan; Wenaweser, Peter; Jüni, Peter; Windecker, Stephan

    2016-12-10

    Our aim was to compare the safety and efficacy of a novel, ultrathin strut, biodegradable polymer sirolimus-eluting stent (BP-SES) with a thin strut, durable polymer everolimus-eluting stent (DP-EES) in a pre-specified subgroup of patients with acute ST-segment elevation myocardial infarction (STEMI) enrolled in the BIOSCIENCE trial. The BIOSCIENCE trial is an investigator-initiated, single-blind, multicentre, randomised non-inferiority trial (NCT01443104). Randomisation was stratified according to the presence or absence of STEMI. The primary endpoint, target lesion failure (TLF), is a composite of cardiac death, target vessel myocardial infarction, and clinically indicated target lesion revascularisation within 12 months. Between February 2012 and May 2013, 407 STEMI patients were randomly assigned to treatment with BP-SES or DP-EES. At one year, TLF occurred in seven (3.4%) patients treated with BP-SES and 17 (8.8%) patients treated with DP-EES (RR 0.38, 95% CI: 0.16-0.91, p=0.024). Rates of cardiac death were 1.5% in the BP-SES group and 4.7% in the DP-EES group (RR 0.31, 95% CI: 0.08-1.14, p=0.062); rates of target vessel myocardial infarction were 0.5% and 2.6% (RR 0.18, 95% CI: 0.02-1.57, p=0.082), respectively, and rates of clinically indicated target lesion revascularisation were 1.5% in the BP-SES group versus 2.1% in the DP-EES group (RR 0.69, 95% CI: 0.16-3.10, p=0.631). There was no difference in the risk of definite stent thrombosis. In this pre-specified subgroup analysis, BP-SES was associated with a lower rate of target lesion failure at one year compared to DP-EES in STEMI patients. These findings require confirmation in a dedicated STEMI trial.

  12. Everolimus-induced Pneumonitis after Drug-eluting Stent Implantation: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Sakamoto, Susumu, E-mail: susumu1029@gmail.com; Kikuchi, Naoshi; Ichikawa, Atsuo; Sano, Go; Satoh, Keita; Sugino, Keishi; Isobe, Kazutoshi; Takai, Yujiro [Toho University School of Medicine, Department of Respiratory Medicine (Japan); Shibuya, Kazutoshi [Toho University School of Medicine, Department of Pathology (Japan); Homma, Sakae [Toho University School of Medicine, Department of Respiratory Medicine (Japan)

    2013-08-01

    Despite the wide use of everolimus as an antineoplastic coating agent for coronary stents to reduce the rate of restenosis, little is known about the health hazards of everolimus-eluting stents (EES). We describe a case of pneumonitis that developed 2 months after EES implantation for angina. Lung pathology demonstrated an organizing pneumonia pattern that responded to corticosteroid therapy. Although the efficacy of EES for ischemic heart disease is well established, EES carries a risk of pneumonitis.

  13. Five-year clinical and functional multislice computed tomography angiographic results after coronary implantation of the fully resorbable polymeric everolimus-eluting scaffold in patients with de novo coronary artery disease

    DEFF Research Database (Denmark)

    Onuma, Yoshinobu; Dudek, Dariusz; Thuesen, Leif

    2013-01-01

    This study sought to demonstrate the 5-year clinical and functional multislice computed tomography angiographic results after implantation of the fully resorbable everolimus-eluting scaffold (Absorb BVS, Abbott Vascular, Santa Clara, California).......This study sought to demonstrate the 5-year clinical and functional multislice computed tomography angiographic results after implantation of the fully resorbable everolimus-eluting scaffold (Absorb BVS, Abbott Vascular, Santa Clara, California)....

  14. Evaluation of XIENCE V everolimus-eluting and Taxus Express2 paclitaxel-eluting coronary stents in patients with jailed side branches from the SPIRIT IV trial at 2 years.

    Science.gov (United States)

    Forrest, John K; Lansky, Alexandra J; Meller, Stephanie M; Hou, Liming; Sood, Poornima; Applegate, Robert J; Wang, John C; Skelding, Kimberly A; Shah, Aakar; Kereiakes, Dean J; Sudhir, Krishnankutty; Cristea, Ecaterina; Yaqub, Manejeh; Stone, Gregg W

    2013-06-01

    The aim of this study was to determine whether patients from the Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System in the Treatment of Patients With de Novo Native Coronary Artery Lesions (SPIRIT) IV trial who underwent percutaneous coronary intervention, who had target lesions with jailed side branches, had improved clinical outcomes when treated with the XIENCE V versus Taxus Express(2) drug-eluting stent. In the SPIRIT III randomized trial, patients with target lesions with jailed side branches after XIENCE V compared with Taxus Express(2) implantation had lower 2-year rates of major adverse cardiac events. The SPIRIT IV trial represents a larger more diverse patient population compared with SPIRIT III. In the large-scale, prospective, multicenter, randomized SPIRIT IV trial, 3,687 patients who underwent coronary stenting with up to 3 de novo native coronary artery lesions were randomized 2:1 to receive XIENCE V versus Taxus Express(2) stents. Two-year clinical outcomes of patients with or without jailed side branches after stenting were compared. A jailed side branch was defined as any side branch >1.0 mm in diameter within the target segment being stented, excluding bifurcations deemed to require treatment. Of the 3,687 patients in SPIRIT IV, a total of 1,426 had side branches that were jailed during angioplasty of the target lesion. Patients with jailed side branches after XIENCE V compared with Taxus Express(2) implantation had significantly lower 2-year rates of target lesion failure (6.5% vs 11.9%, p = 0.001), major adverse cardiac events (6.6% vs 12.2%, p = 0.0008), ischemia-driven target vessel revascularization (4.1% vs 7.9%, p = 0.004), and stent thrombosis (0.6% vs 2.8%, p = 0.001). In conclusion, patients with jailed side branches after stenting with XIENCE V compared to Taxus Express(2) devices had superior clinical outcomes at 2 years in the large-scale randomized SPIRIT IV trial. Copyright © 2013 Elsevier Inc. All

  15. Biodegradable-Polymer Biolimus-Eluting Stents versus Durable-Polymer Everolimus-Eluting Stents at One-Year Follow-Up: A Registry-Based Cohort Study.

    Science.gov (United States)

    Parsa, Ehsan; Saroukhani, Sepideh; Majlessi, Fereshteh; Poorhosseini, Hamidreza; Lofti-Tokaldany, Masoumeh; Jalali, Arash; Salarifar, Mojtaba; Nematipour, Ebrahim; Alidoosti, Mohammad; Aghajani, Hassan; Amirzadegan, Alireza; Kassaian, Seyed Ebrahim

    2016-04-01

    We compared outcomes of percutaneous coronary intervention patients who received biodegradable-polymer biolimus-eluting stents with those who received durable-polymer everolimus-eluting stents. At Tehran Heart Center, we performed a retrospective analysis of the data from January 2007 through December 2011 on 3,270 consecutive patients with coronary artery disease who underwent percutaneous coronary intervention with the biodegradable-polymer biolimus-eluting stent or the durable-polymer everolimus-eluting stent. We excluded patients with histories of coronary artery bypass grafting or percutaneous coronary intervention, acute ST-segment-elevation myocardial infarction, or the implantation of 2 different stent types. Patients were monitored for 12 months. The primary endpoint was a major adverse cardiac event, defined as a composite of death, nonfatal myocardial infarction, and target-vessel and target-lesion revascularization. Durable-polymer everolimus-eluting stents were implanted in 2,648 (81%) and biodegradable-polymer biolimus-eluting stents in 622 (19%) of the study population. There was no significant difference between the 2 groups (2.7% vs 2.7%; P=0.984) in the incidence of major adverse cardiac events. The cumulative adjusted probability of major adverse cardiac events in the biodegradable-polymer biolimus-eluting stent group did not differ from that of such events in the durable-polymer everolimus-eluting stent group (hazard ratio=0.768; 95% confidence interval, 0.421-1.44; P=0.388). We conclude that in our patients the biodegradable-polymer biolimus-eluting stent was as effective and safe, during the 12-month follow-up period, as was the durable-polymer everolimus-eluting stent.

  16. A randomized comparison of novel bioresorbable polymer sirolimus-eluting stent and durable polymer everolimus-eluting stent in patients with acute coronary syndromes: The CENTURY II high risk ACS substudy

    International Nuclear Information System (INIS)

    Jiménez, Victor A.; Iñiguez, Andrés; Baz, José A.; Valdés, Mariano; Ortiz, Alberto; Vuilliomenet, André; Mainar, Vicente; Dudek, Dariusz; Banai, Shmuel; Tüller, David; Bonnet, Jean-Louis; De Miguel, Antonio; Bastos, Guillermo; Wijns, William; Saito, Shigeru

    2016-01-01

    Background: To investigate clinical outcomes of percutaneous coronary intervention using a sirolimus-eluting stent with bioresorbable polymer, Ultimaster (BP-SES) compared with a permanent polymer everolimus-eluting stent, Xience (PP-EES) in patients with high risk (ST-segment elevation and non-ST-segment elevation myocardial infarction) acute coronary syndromes (ACS) enrolled in the CENTURY II trial. Methods: CENTURY II is a prospective, multicenter, randomized, single blind, controlled trial comparing BP-SES and PP-EES, with primary endpoint of target lesion failure (TLF) at 9 month post-stent implantation. Out of 1123 patients enrolled in CENTURY II trial, 264 high risk ACS patients were included in this subgroup analysis, and the clinical outcomes including target lesion failure (TLF), target vessel failure (TVF), cardiac death, myocardial infarction, and stent thrombosis were evaluated at 24 months. Results: The baseline clinical, angiographic and procedural characteristics were similar between two groups. At 24 months, TLF occurred in 6.3% of patients receiving a BP-SES and 6.5% of patients receiving a PP-EES (P = 0.95); TVF was 6.3% in patients receiving a BP-SES and 9.4% in patients receiving a PP-EES (P = 0.36). There were no significant differences in cardiac death, myocardial infarction and stent thrombosis rate. Conclusions: BP-SES achieved similar safety and efficacy outcomes as PP-EES in this ACS subgroup of CENTURY II study, at 24-month follow-up. This finding is hypothesis-generating and needs to be confirmed in larger trials with longer follow-up. - Highlights: • This study reported the 24-month clinical outcomes of new-generation BP-SES compared with PP-EES in ACS subgroup from CENTURY II study. • This is a pre-specified subgroup analysis of a large randomized, prospective, multicenter clinical trial. • The BP-SES showed good and comparable clinical performance as PP-EES at 24 months. • This substudy has a relatively small sample size and

  17. A randomized comparison of novel bioresorbable polymer sirolimus-eluting stent and durable polymer everolimus-eluting stent in patients with acute coronary syndromes: The CENTURY II high risk ACS substudy

    Energy Technology Data Exchange (ETDEWEB)

    Jiménez, Victor A., E-mail: victor.alfonso.jimenez.diaz@sergas.es [Interventional Cardiology Unit, Cardiology Department, Hospital Alvaro Cunqueiro, University Hospital of Vigo, Vigo (Spain); Iñiguez, Andrés; Baz, José A. [Interventional Cardiology Unit, Cardiology Department, Hospital Alvaro Cunqueiro, University Hospital of Vigo, Vigo (Spain); Valdés, Mariano [Hospital Universitario V. Arrixaca, Murcia (Spain); Ortiz, Alberto [Interventional Cardiology Unit, Cardiology Department, Hospital Alvaro Cunqueiro, University Hospital of Vigo, Vigo (Spain); Vuilliomenet, André [Kantonsspital Aarau, Aarau (Switzerland); Mainar, Vicente [Department of Cardiology, University General Hospital of Alicante, Alicante (Spain); Dudek, Dariusz [Department of Interventional Cardiology, Jagiellonian University Medical College, Krakow (Poland); Banai, Shmuel [Tel Aviv Sourasky Medical Centre, Tel Aviv (Israel); Tüller, David [Department of Cardiology, Stadtspital Triemli, Zürich (Switzerland); Bonnet, Jean-Louis [Department of Cardiology, Hospital La Timone, Marseille (France); De Miguel, Antonio; Bastos, Guillermo [Interventional Cardiology Unit, Cardiology Department, Hospital Alvaro Cunqueiro, University Hospital of Vigo, Vigo (Spain); Wijns, William [Cardiovascular Center Aalst, OLV Hospital, Aalst (Belgium); Saito, Shigeru [Department of Cardiology and Catheterization Laboratory, Shonan Kamakura General Hospital, Kamakura (Japan)

    2016-09-15

    Background: To investigate clinical outcomes of percutaneous coronary intervention using a sirolimus-eluting stent with bioresorbable polymer, Ultimaster (BP-SES) compared with a permanent polymer everolimus-eluting stent, Xience (PP-EES) in patients with high risk (ST-segment elevation and non-ST-segment elevation myocardial infarction) acute coronary syndromes (ACS) enrolled in the CENTURY II trial. Methods: CENTURY II is a prospective, multicenter, randomized, single blind, controlled trial comparing BP-SES and PP-EES, with primary endpoint of target lesion failure (TLF) at 9 month post-stent implantation. Out of 1123 patients enrolled in CENTURY II trial, 264 high risk ACS patients were included in this subgroup analysis, and the clinical outcomes including target lesion failure (TLF), target vessel failure (TVF), cardiac death, myocardial infarction, and stent thrombosis were evaluated at 24 months. Results: The baseline clinical, angiographic and procedural characteristics were similar between two groups. At 24 months, TLF occurred in 6.3% of patients receiving a BP-SES and 6.5% of patients receiving a PP-EES (P = 0.95); TVF was 6.3% in patients receiving a BP-SES and 9.4% in patients receiving a PP-EES (P = 0.36). There were no significant differences in cardiac death, myocardial infarction and stent thrombosis rate. Conclusions: BP-SES achieved similar safety and efficacy outcomes as PP-EES in this ACS subgroup of CENTURY II study, at 24-month follow-up. This finding is hypothesis-generating and needs to be confirmed in larger trials with longer follow-up. - Highlights: • This study reported the 24-month clinical outcomes of new-generation BP-SES compared with PP-EES in ACS subgroup from CENTURY II study. • This is a pre-specified subgroup analysis of a large randomized, prospective, multicenter clinical trial. • The BP-SES showed good and comparable clinical performance as PP-EES at 24 months. • This substudy has a relatively small sample size and

  18. Long-term forecasting and comparison of mortality in the Evaluation of the Xience Everolimus Eluting Stent vs. Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization (EXCEL) trial: prospective validation of the SYNTAX Score II.

    Science.gov (United States)

    Campos, Carlos M; van Klaveren, David; Farooq, Vasim; Simonton, Charles A; Kappetein, Arie-Pieter; Sabik, Joseph F; Steyerberg, Ewout W; Stone, Gregg W; Serruys, Patrick W

    2015-05-21

    To prospectively validate the SYNTAX Score II and forecast the outcomes of the randomized Evaluation of the Xience Everolimus-Eluting Stent Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization (EXCEL) Trial. Evaluation of the Xience Everolimus Eluting Stent vs. Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization is a prospective, randomized multicenter trial designed to establish the efficacy and safety of percutaneous coronary intervention (PCI) with the everolimus-eluting stent compared with coronary artery bypass graft (CABG) surgery in subjects with unprotected left-main coronary artery (ULMCA) disease and low-intermediate anatomical SYNTAX scores (EXCEL, the SYNTAX Score II was prospectively applied to predict 4-year mortality in the CABG and PCI arms. The 95% prediction intervals (PIs) for mortality were computed using simulation with bootstrap resampling (10 000 times). For the entire study cohort, the 4-year predicted mortalities were 8.5 and 10.5% in the PCI and CABG arms, respectively [odds ratios (OR) 0.79; 95% PI 0.43-1.50). In subjects with low (≤22) anatomical SYNTAX scores, the predicted OR was 0.69 (95% PI 0.34-1.45); in intermediate anatomical SYNTAX scores (23-32), the predicted OR was 0.93 (95% PI 0.53-1.62). Based on 4-year mortality predictions in EXCEL, clinical characteristics shifted long-term mortality predictions either in favour of PCI (older age, male gender and COPD) or CABG (younger age, lower creatinine clearance, female gender, reduced left ventricular ejection fraction). The SYNTAX Score II indicates at least an equipoise for long-term mortality between CABG and PCI in subjects with ULMCA disease up to an intermediate anatomical complexity. Both anatomical and clinical characteristics had a clear impact on long-term mortality predictions and decision making between CABG and PCI. Published on behalf of the European Society of Cardiology. All rights reserved. © The

  19. Economic Outcomes of Bioresorbable Vascular Scaffolds Versus Everolimus-Eluting Stents in Patients Undergoing Percutaneous Coronary Intervention: 1-Year Results From the ABSORB III Trial.

    Science.gov (United States)

    Baron, Suzanne J; Lei, Yang; Chinnakondepalli, Khaja; Vilain, Katherine; Magnuson, Elizabeth A; Kereiakes, Dean J; Ellis, Stephen G; Stone, Gregg W; Cohen, David J

    2017-04-24

    The purpose of this study was to evaluate the economic impact of the Absorb bioresorbable vascular scaffold compared with the Xience everolimus-eluting stent in patients undergoing percutaneous coronary intervention. The ABSORB III trial (Everolimus-Eluting Bioresorbable Scaffolds for Coronary Artery Disease) demonstrated that the Absorb scaffold was noninferior to the Xience stent with respect to target lesion failure at 1 year. Whether health care costs differ between the Absorb scaffold and the Xience stent is unknown. We performed a prospective health economic study alongside the ABSORB III trial, in which patients undergoing percutaneous coronary intervention for stable or unstable angina were randomized to receive the Absorb scaffold (n = 1,322) or Xience stent (n = 686). Resource use data were collected through 1 year of follow-up. Costs were assessed using resource-based accounting (for procedures), MedPAR data (for other index hospitalization costs), and Medicare reimbursements (for follow-up costs and physician fees). Initial procedural costs were higher with the Absorb scaffold than the Xience stent ($6,316 ± 1,892 vs. $6,103 ± 1,895; p = 0.02), driven mainly by greater balloon catheter use and the higher cost of the scaffold in the Absorb group. Nonetheless, index hospitalization costs ($15,035 ± 2,992 for Absorb vs. $14,903 ± 3,449 for Xience; p = 0.37) and total 1-year costs ($17,848 ± 6,110 for Absorb vs. $17,498 ± 7,411 for Xience; p = 0.29) were similar between the 2 groups. Although initial procedural costs were higher with the Absorb scaffold, there were no differences in total 1-year health care costs between the 2 cohorts. Longer term follow-up is needed to determine whether meaningful cost savings emerge after scaffold resorption. (A Clinical Evaluation of Absorb™ BVS, the Everolimus-Eluting Bioresorbable Vascular Scaffold in the Treatment of Subjects With de Novo Native Coronary Artery Lesions; NCT01751906). Copyright © 2017

  20. Absorb bioresorbable vascular scaffold versus everolimus-eluting metallic stent in ST-segment elevation myocardial infarction: 1-year results of a propensity score matching comparison: the BVS-EXAMINATION Study (bioresorbable vascular scaffold-a clinical evaluation of everolimus eluting coronary stents in the treatment of patients with ST-segment elevation myocardial infarction).

    Science.gov (United States)

    Brugaletta, Salvatore; Gori, Tommaso; Low, Adrian F; Tousek, Petr; Pinar, Eduardo; Gomez-Lara, Josep; Scalone, Giancarla; Schulz, Eberhard; Chan, Mark Y; Kocka, Viktor; Hurtado, Jose; Gomez-Hospital, Juan Antoni; Münzel, Thomas; Lee, Chi-Hang; Cequier, Angel; Valdés, Mariano; Widimsky, Petr; Serruys, Patrick W; Sabaté, Manel

    2015-01-01

    The purpose of this study was to compare the 1-year outcome between bioresorbable vascular scaffold (BVS) and everolimus-eluting metallic stent (EES) in ST-segment elevation myocardial infarction (STEMI) patients. The Absorb BVS (Abbott Vascular, Santa Clara, California) is a polymeric scaffold approved for treatment of stable coronary lesions. Limited and not randomized data are available on its use in ST-segment elevation myocardial infarction (STEMI) patients. This study included 290 consecutive STEMI patients treated by BVS, compared with either 290 STEMI patients treated with EES or 290 STEMI patients treated with bare-metal stents (BMS) from the EXAMINATION (A Clinical Evaluation of Everolimus Eluting Coronary Stents in the Treatment of Patients With ST-segment Elevation Myocardial Infarction) trial, by applying propensity score matching. The primary endpoint was a device-oriented endpoint (DOCE), including cardiac death, target vessel myocardial infarction, and target lesion revascularization, at 1-year follow-up. Device thrombosis, according to the Academic Research Consortium criteria, was also evaluated. The cumulative incidence of DOCE did not differ between the BVS and EES or BMS groups either at 30 days (3.1% vs. 2.4%, hazard ratio [HR]: 1.31 [95% confidence interval (CI): 0.48 to 3.52], p = 0.593; vs. 2.8%, HR: 1.15 [95% CI: 0.44 to 2.30], p = 0.776, respectively) or at 1 year (4.1% vs. 4.1%, HR: 0.99 [95% CI: 0.23 to 4.32], p = 0.994; vs. 5.9%, HR: 0.50 [95% CI: 0.13 to 1.88], p = 0.306, respectively). Definite/probable BVS thrombosis rate was numerically higher either at 30 days (2.1% vs. 0.3%, p = 0.059; vs. 1.0%, p = 0.324, respectively) or at 1 year (2.4% vs. 1.4%, p = 0.948; vs. 1.7%, p = 0.825, respectively), as compared with EES or BMS. At 1-year follow-up, STEMI patients treated with BVS showed similar rates of DOCE compared with STEMI patients treated with EES or BMS, although rate of scaffolds thrombosis, mostly clustered in the early phase

  1. Arterial healing following primary PCI using the Absorb everolimus-eluting bioresorbable vascular scaffold (Absorb BVS) versus the durable polymer everolimus-eluting metallic stent (XIENCE) in patients with acute ST-elevation myocardial infarction

    DEFF Research Database (Denmark)

    Räber, Lorenz; Onuma, Yoshinobu; Brugaletta, Salvatore

    2015-01-01

    Aims: The Absorb bioresorbable vascular scaffold (Absorb BVS) provides similar clinical outcomes compared with a durable polymer-based everolimus-eluting metallic stent (EES) in stable coronary artery disease patients. ST-elevation myocardial infarction (STEMI) lesions have been associated with d...

  2. A randomized comparison of a durable polymer Everolimus-eluting stent with a bare metal coronary stent: The SPIRIT first trial

    NARCIS (Netherlands)

    Serruys, Patrick W.; Ong, Andrew T. L.; Piek, Jan J.; Neumann, Franz-Josef; van der Giessen, Willem J.; Wiemer, Marcus; Zeiher, Andreas; Grube, Eberhard; Haase, Jürgen; Thuesen, Leif; Hamm, Christian; Otto-Terlouw, Patricia C.

    2005-01-01

    Background: Everolimus is a sirolimus analogue with similar efficacy in animal models, and has been previously successfully tested in humans using an erodable polymer.Methods: This first-in-man single blind multi-centre randomized controlled trial assessed the safety and efficacy of everolimus

  3. 1-year clinical outcomes of diabetic patients treated with everolimus-eluting bioresorbable vascular scaffolds: a pooled analysis of the ABSORB and the SPIRIT trials.

    Science.gov (United States)

    Muramatsu, Takashi; Onuma, Yoshinobu; van Geuns, Robert-Jan; Chevalier, Bernard; Patel, Tejas M; Seth, Ashok; Diletti, Roberto; García-García, Hector M; Dorange, Cécile C; Veldhof, Susan; Cheong, Wai-Fung; Ozaki, Yukio; Whitbourn, Robert; Bartorelli, Antonio; Stone, Gregg W; Abizaid, Alexandre; Serruys, Patrick W

    2014-05-01

    The aim of this study was to evaluate 1-year clinical outcomes of diabetic patients treated with the Absorb bioresorbable vascular scaffold (BVS). Clinical outcomes of diabetic patients after BVS implantation have been unreported. This study included 101 patients in the ABSORB Cohort B trial and the first consecutive 450 patients with 1 year of follow-up in the ABSORB EXTEND trial. A total of 136 diabetic patients were compared with 415 nondiabetic patients. In addition, 882 diabetic patients treated with everolimus-eluting metal stents (EES) in pooled data from the SPIRIT trials (SPIRIT FIRST [Clinical Trial of the Abbott Vascular XIENCE V Everolimus Eluting Coronary Stent System], SPIRIT II [A Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System], SPIRIT III [Clinical Trial of the XIENCE V Everolimus Eluting Coronary Stent System (EECSS)], SPIRIT IV Clinical Trial [Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System]) were used for the comparison by applying propensity score matching. The primary endpoint was a device-oriented composite endpoint (DoCE), including cardiac death, target vessel myocardial infarction, and target lesion revascularization at 1-year follow-up. The cumulative incidence of DoCE did not differ between diabetic and nondiabetic patients treated with the BVS (3.7% vs. 5.1%, p = 0.64). Diabetic patients treated with the BVS had a similar incidence of the DoCE compared with diabetic patients treated with EES in the matched study group (3.9% for the BVS vs. 6.4% for EES, p = 0.38). There were no differences in the incidence of definite or probable scaffold/stent thrombosis (0.7% for both diabetic and nondiabetic patients with the BVS; 1.0% for diabetic patients with the BVS vs. 1.7% for diabetic patients with EES in the matched study group). In the present analyses, diabetic patients treated with the BVS showed similar rates of DoCEs compared with nondiabetic patients treated with the BVS and

  4. 3-Year Clinical Follow-Up of the RIBS IV Clinical Trial: A Prospective Randomized Study of Drug-Eluting Balloons Versus Everolimus-Eluting Stents in Patients With In-Stent Restenosis in Coronary Arteries Previously Treated With Drug-Eluting Stents.

    Science.gov (United States)

    Alfonso, Fernando; Pérez-Vizcayno, María José; Cuesta, Javier; García Del Blanco, Bruno; García-Touchard, Arturo; López-Mínguez, José Ramón; Masotti, Mónica; Zueco, Javier; Cequier, Angel; Velázquez, Maite; Moreno, Raúl; Mainar, Vicente; Domínguez, Antonio; Moris, Cesar; Molina, Eduardo; Rivero, Fernando; Jiménez-Quevedo, Pilar; Gonzalo, Nieves; Fernández-Pérez, Cristina

    2018-05-28

    This study sought to compare the long-term safety and efficacy of drug-eluting balloons (DEB) and everolimus-eluting stents (EES) in patients with in-stent restenosis (ISR) of drug-eluting stents (DES). Treatment of patients with DES-ISR remains a challenge. The RIBS IV (Restenosis Intra-Stent of Drug-Eluting Stents: Drug-Eluting Balloons vs Everolimus-Eluting Stents) trial is a prospective multicenter randomized clinical trial comparing DEB and EES in patients with DES-ISR. The pre-specified comparison of the 3-year clinical outcomes obtained with these interventions is the main objective of the present study. A total of 309 patients with DES-ISR were randomized to DEB (n = 154) or EES (n = 155). At angiographic follow-up, the in-segment minimal lumen diameter was larger in the EES arm (2.03 ± 0.7 mm vs. 1.80 ± 0.6 mm; p 1 year) target lesion revascularization (2.6% vs. 4%) and target vessel revascularization (4% vs. 6.6%) was similar in the 2 arms. Rates of cardiac death (3.9% vs. 3.2%), myocardial infarction (2.6% vs. 4.5%), and stent thrombosis (1.3% vs. 2.6%) at 3 years were also similar in both arms. The 3-year clinical follow-up of this randomized clinical trial demonstrates that in patients with DES-ISR, EES reduce the need for repeat interventions compared with DEB. (Restenosis Intra-Stent of Drug-Eluting Stents: Drug-Eluting Balloons vs Everolimus-Eluting Stents [RIBS IV]; NCT01239940). Published by Elsevier Inc.

  5. Intimal hyperplasia and vascular remodeling after everolimus-eluting and sirolimus-eluting stent implantation in diabetic patients the randomized diabetes and drug-eluting stent (DiabeDES) IV intravascular ultrasound trial

    DEFF Research Database (Denmark)

    Antonsen, Lisbeth; Maeng, Michael; Thayssen, Per

    2013-01-01

    OBJECTIVE: To evaluate the effects of the everolimus-eluting Xience™/Promus™ stent (EES) and the sirolimus-eluting Cypher™ stent (SES) on intimal hyperplasia (IH) in diabetic patients. BACKGROUND: Patients with diabetes mellitus have increased risk of in-stent restenosis after coronary stent...... implantation due to intimal hyperplasia (IH). METHODS: In a sub study of the Randomized Comparison of Everolimus-Eluting and Sirolimus-Eluting Stents in Patients Treated with Percutaneous Coronary Intervention (SORT OUT IV trial), serial intravascular ultrasound (IVUS) 10-month follow-up data were available...... in 88 patients, including 48 EES and 40 SES treated patients. IVUS endpoints included IH volume, in-stent % volume obstruction and changes in external elastic membrane (EEM) volume. RESULTS: Compared with the SES group, IH volume was increased in the EES group [median (interquartile range): 2.8 mm(3) (0...

  6. Differentiated analysis of an everolimus-eluting stent and a paclitaxel-eluting stent among higher risk subgroups for restenosis: results from the SPIRIT II trial.

    Science.gov (United States)

    Khattab, Ahmed A; Richardt, Gert; Verin, Vitali; Kelbaek, Henning; Macaya, Carlos; Berland, Jacques; Miquel-Hebert, Karine; Dorange, Cécile; Serruys, Patrick W

    2008-03-01

    Restenosis is higher among certain subpopulations when subjected to percutaneous coronary interventions even when using drug-eluting stents. The randomised SPIRIT II trial demonstrated the superiority of the XIENCE V Everolimus Eluting Coronary Stent System over the TAXUS Paclitaxel-Eluting Stent System in terms of in-stent late loss at six months among 300 patients treated for de novo native coronary artery lesions. In this post-hoc analysis of SPIRIT II we focused on six-month angiographic outcomes of diabetic patients (n=69), left anterior descending arteries (n=149), long lesions >20 mm (n=43), small vessels B2 and C lesions (n=233). In-stent late loss was consistently less among all subgroups when treated by everolimus-eluting stents compared to paclitaxel-eluting stents: diabetics 0.15+/-0.26 mm versus 0.39+/-0.34 mm, p=0.006; LAD 0.12+/-0.23 mm versus 0.44+/-0.37 mm, pB2/C lesions 0.12+/-0.31 mm versus 0.36+/-0.36 mm, pSPIRIT II trial population.

  7. Safety and Efficacy of Everolimus- Versus Sirolimus-Eluting Stents

    DEFF Research Database (Denmark)

    Jensen, Lisette Okkels; Thayssen, Per; Christiansen, Evald Høj

    2016-01-01

    BACKGROUND: Long-term safety and efficacy for everolimus-eluting stents (EES) versus those of sirolimus-eluting stents (SES) are unknown. OBJECTIVES: This study compared 5-year outcomes for EES with those for SES from the SORT OUT IV (Scandinavian Organization for Randomized Trials with Clinical...... rate was lower with EES (HR: 0.71, 95% CI: 0.55 to 0.90; p = 0.006; p interaction = 0.12). Definite stent thrombosis was lower with EES (0.4%) than with SES (2.0%; HR: 0.18, 95% CI: 0.07 to 0.46), with a lower risk of very late definite stent thrombosis in the EES group (0.2% vs. 1.4%, respectively; HR...... in Non-selected Patients With Coronary Heart Disease [SORT OUT IV]; NCT00552877)....

  8. A sirolimus-eluting bioabsorbable polymer-coated stent (MiStent) versus an everolimus-eluting durable polymer stent (Xience) after percutaneous coronary intervention (DESSOLVE III): a randomised, single-blind, multicentre, non-inferiority, phase 3 trial

    NARCIS (Netherlands)

    de Winter, Robbert J.; Katagiri, Yuki; Asano, Taku; Milewski, Krzysztof P.; Lurz, Philipp; Buszman, Pawel; Jessurun, Gillian A. J.; Koch, Karel T.; Troquay, Roland P. T.; Hamer, Bas J. B.; Ophuis, Ton Oude; Wöhrle, Jochen; Wyderka, Rafał; Cayla, Guillaume; Hofma, Sjoerd H.; Levesque, Sébastien; Żurakowski, Aleksander; Fischer, Dieter; Kośmider, Maciej; Goube, Pascal; Arkenbout, E. Karin; Noutsias, Michel; Ferrari, Markus W.; Onuma, Yoshinobu; Wijns, William; Serruys, Patrick W.

    2018-01-01

    Background MiStent is a drug-eluting stent with a fully absorbable polymer coating containing and embedding a microcrystalline form of sirolimus into the vessel wall. It was developed to overcome the limitation of current durable polymer drug-eluting stents eluting amorphous sirolimus. The clinical

  9. Is quantitative coronary angiography reliable in assessing the late lumen loss of the everolimus-eluting bioresorbable polylactide scaffold in comparison with the cobalt-chromium metallic stent?

    NARCIS (Netherlands)

    Sotomi, Yohei; Onuma, Yoshinobu; Miyazaki, Yosuke; Asano, Taku; Katagiri, Yuki; Tenekecioglu, Erhan; Jonker, Hans; Dijkstra, Jouke; de Winter, Robbert J.; Wykrzykowska, Joanna J.; Stone, Gregg W.; Popma, Jeffrey J.; Kozuma, Ken; Tanabe, Kengo; Serruys, Patrick W.; Kimura, Takeshi

    2017-01-01

    Aims: Immediately after stent/scaffold implantation, quantitative coronary angiography (QCA) in comparison to optical coherence tomography (OCT) more severely underestimates the lumen diameter (LD) in Absorb than in XIENCE. This OCT-QCA discrepancy has not been evaluated at long-term follow-up. The

  10. Randomized Comparison of Everolimus-Eluting and Sirolimus-Eluting Stents in Patients Treated With Percutaneous Coronary Intervention: The Scandinavian Organization for Randomized Trials With Clinical Outcome IV (SORT OUT IV)

    DEFF Research Database (Denmark)

    Okkels Jensen, Lisette; Thayssen, Per; Hansen, Henrik Steen

    2012-01-01

    was a composite of safety (cardiac death, myocardial infarction, definite stent thrombosis) and efficacy (target vessel revascularization) parameters. The noninferiority criterion was a risk difference of 0.015. Intention-to-treat analyses were done at 9- and 18-month follow-ups. A total of 1390 patients were.......71-1.23). At the 9-month follow-up, the rate of definite stent thrombosis was higher in the sirolimus-eluting group (2 patients [0.1%] versus 9 patients [0.7%]; hazard ratio, 0.22; 95% confidence interval, 0.05-1.02). At the 18-month follow-up, this difference was sustained (3 patients [0.2%] versus 12 patients [0...

  11. The Impact of Post-Procedural Asymmetry, Expansion, and Eccentricity of Bioresorbable Everolimus-Eluting Scaffold and Metallic Everolimus-Eluting Stent on Clinical Outcomes in the ABSORB II Trial.

    Science.gov (United States)

    Suwannasom, Pannipa; Sotomi, Yohei; Ishibashi, Yuki; Cavalcante, Rafael; Albuquerque, Felipe N; Macaya, Carlos; Ormiston, John A; Hill, Jonathan; Lang, Irene M; Egred, Mohaned; Fajadet, Jean; Lesiak, Maciej; Tijssen, Jan G; Wykrzykowska, Joanna J; de Winter, Robbert J; Chevalier, Bernard; Serruys, Patrick W; Onuma, Yoshinobu

    2016-06-27

    The study sought to investigate the relationship between post-procedural asymmetry, expansion, and eccentricity indices of metallic everolimus-eluting stent (EES) and bioresorbable vascular scaffold (BVS) and their respective impact on clinical events at 1-year follow-up. Mechanical properties of a fully BVS are inherently different from those of permanent metallic stent. The ABSORB II (A bioresorbable everolimus-eluting scaffold versus a metallic everolimus-eluting stent for ischaemic heart disease caused by de-novo native coronary artery lesions) trial compared the BVS and metallic EES in the treatment of a de novo coronary artery stenosis. Protocol-mandated intravascular ultrasound imaging was performed pre- and post-procedure in 470 patients (162 metallic EES and 308 BVS). Asymmetry index (AI) was calculated per lesion as: (1 - minimum scaffold/stent diameter/maximum scaffold/stent diameter). Expansion index and optimal scaffold/stent expansion followed the definition of the MUSIC (Multicenter Ultrasound Stenting in Coronaries) study. Eccentricity index (EI) was calculated as the ratio of minimum and maximum scaffold/stent diameter per cross section. The incidence of device-oriented composite endpoint (DoCE) was collected. Post-procedure, the metallic EES group was more symmetric and concentric than the BVS group. Only 8.0% of the BVS arm and 20.0% of the metallic EES arm achieved optimal scaffold/stent expansion (p 0.30 is an independent predictor of DoCE (hazard ratio: 3.43; 95% confidence interval: 1.08 to 10.92; p = 0.037). BVS implantation is more frequently associated with post-procedural asymmetric and eccentric morphology compared to metallic EES. Post-procedural devices asymmetry were independently associated with DoCE following percutaneous coronary intervention. However, this approach should be viewed as hypothesis generating due to low event rates. (ABSORB II Randomized Controlled Trial [ABSORB II]; NCT01425281). Copyright © 2016 American

  12. Evaluation of the short- and long-term safety and therapy outcomes of the everolimus-eluting bioresorbable vascular scaffold system in patients with coronary artery stenosis: Rationale and design of the German–Austrian ABSORB RegIstRy (GABI-R)

    Energy Technology Data Exchange (ETDEWEB)

    Nef, Holger, E-mail: holger.nef@innere.med.uni-giessen.de [University of Giessen, Medizinische Klinik I, Department of Cardiology, Giessen (Germany); Wiebe, Jens [University of Giessen, Medizinische Klinik I, Department of Cardiology, Giessen (Germany); Achenbach, Stefan [University of Erlangen, Medizinische Klinik II, Department of Cardiology, Erlangen (Germany); Münzel, Thomas [Department of Medicine II, University Medical Center, Johannes Gutenberg University Mainz, Mainz (Germany); Naber, Christoph [Klinik für Kardiologie und Angiologie, Elisabeth-Krankenhaus, Essen (Germany); Richardt, Gert [Herzzentrum, Segeberger Kliniken GmbH, Bad Segeberg (Germany); Mehilli, Julinda [Department of Cardiology, Klinikum Großhadern, Ludwig- Maximilian Universität, Munich (Germany); Wöhrle, Jochen [Department of Internal Medicine II, University of Ulm, Ulm (Germany); Neumann, Till; Biermann, Janine [University of Essen, Department of Cardiology, Essen (Germany); Zahn, Ralf [Abteilung für Kardiologie, Herzzentrum Ludwigshafen, Ludwigshafen (Germany); Kastner, Johannes [Department of Cardiology, University of Vienna Medical School, Vienna (Austria); Schmermund, Axel [CCB, Cardioangiologisches Centrum Bethanien, Frankfurt (Germany); Pfannebecker, Thomas [Abbott Vascular Deutschland GmbH, Wetzlar (Germany); Schneider, Steffen; Limbourg, Tobias [Institut für Herzinfarktforschung, Ludwigshafen (Germany); Hamm, Christian W. [University of Giessen, Medizinische Klinik I, Department of Cardiology, Giessen (Germany); Kerckhoff Heart and Thorax Center, Department of Cardiology, Bad Nauheim (Germany)

    2016-01-15

    Background: Third-generation drug-eluting metal stents are the gold standard for treatment of coronary artery disease. The permanent metallic caging of the vessel, however, can result in limited vasomotion, chronic inflammation, and late expansive remodeling, conditions that can lead to late and very late stent thrombosis. The development of bioresorbable scaffolds (BRSs) promises advantages over metal stents due to complete biodegradation within 2–4 years. Theoretically, since vessel scaffolding is temporary and no permanent implant remains in the vessel, BRSs, as opposed to metal stents, once degraded would no longer be potential triggers for stent-related adverse events or side effects. Methods/design: The short- and long-term outcome after implantation of an everolimus-eluting, poly-L-lactic acid-based bioresorbable scaffold system (ABSORB, Abbott Vascular, Santa Clara, CA, USA) in the world-wide greatest all-comers cohort will be evaluated in the prospective, non-interventional, multicenter German–Austrian ABSORB RegIstRy (GABI-R). GABI-R will include over 5000 patients from about 100 study sites in Austria and Germany. Safety endpoints such as cardiac death, myocardial infarction, and clinically driven percutaneous or surgical target lesion and vessel revascularization will be evaluated during hospitalization and in the follow-up period (minimum of 5 years). Conclusion: Although two randomized controlled trials and several registries have documented safety and efficacy as well as non-inferiority of this everolimus-eluting ABSORB device compared with drug-eluting metal stents, the current knowledge regarding clinical application, treatment success, and long-term safety of using this BRS in daily routine is limited. Thus, the goal of GABI-R is to address this lack of information. - Highlights: • The GABI-R addresses a lack of data about bioresorbable scaffolds in daily practice. • 5000 patients with minimal in- and exclusion criteria at 100 sites will

  13. Evaluation of the short- and long-term safety and therapy outcomes of the everolimus-eluting bioresorbable vascular scaffold system in patients with coronary artery stenosis: Rationale and design of the German–Austrian ABSORB RegIstRy (GABI-R)

    International Nuclear Information System (INIS)

    Nef, Holger; Wiebe, Jens; Achenbach, Stefan; Münzel, Thomas; Naber, Christoph; Richardt, Gert; Mehilli, Julinda; Wöhrle, Jochen; Neumann, Till; Biermann, Janine; Zahn, Ralf; Kastner, Johannes; Schmermund, Axel; Pfannebecker, Thomas; Schneider, Steffen; Limbourg, Tobias; Hamm, Christian W.

    2016-01-01

    Background: Third-generation drug-eluting metal stents are the gold standard for treatment of coronary artery disease. The permanent metallic caging of the vessel, however, can result in limited vasomotion, chronic inflammation, and late expansive remodeling, conditions that can lead to late and very late stent thrombosis. The development of bioresorbable scaffolds (BRSs) promises advantages over metal stents due to complete biodegradation within 2–4 years. Theoretically, since vessel scaffolding is temporary and no permanent implant remains in the vessel, BRSs, as opposed to metal stents, once degraded would no longer be potential triggers for stent-related adverse events or side effects. Methods/design: The short- and long-term outcome after implantation of an everolimus-eluting, poly-L-lactic acid-based bioresorbable scaffold system (ABSORB, Abbott Vascular, Santa Clara, CA, USA) in the world-wide greatest all-comers cohort will be evaluated in the prospective, non-interventional, multicenter German–Austrian ABSORB RegIstRy (GABI-R). GABI-R will include over 5000 patients from about 100 study sites in Austria and Germany. Safety endpoints such as cardiac death, myocardial infarction, and clinically driven percutaneous or surgical target lesion and vessel revascularization will be evaluated during hospitalization and in the follow-up period (minimum of 5 years). Conclusion: Although two randomized controlled trials and several registries have documented safety and efficacy as well as non-inferiority of this everolimus-eluting ABSORB device compared with drug-eluting metal stents, the current knowledge regarding clinical application, treatment success, and long-term safety of using this BRS in daily routine is limited. Thus, the goal of GABI-R is to address this lack of information. - Highlights: • The GABI-R addresses a lack of data about bioresorbable scaffolds in daily practice. • 5000 patients with minimal in- and exclusion criteria at 100 sites will

  14. Safety and efficacy of everolimus-eluting stents for bare-metal in-stent restenosis

    Energy Technology Data Exchange (ETDEWEB)

    Ota, Hideaki [Division of Interventional Cardiology, MedStar Washington Hospital Center, Washington, DC 20010 (United States); Mahmoudi, Michael [University of Surrey, Guildford Road, Surrey, GU2-7XH (United Kingdom); Torguson, Rebecca; Satler, Lowell F.; Suddath, William O.; Pichard, Augusto D. [Division of Interventional Cardiology, MedStar Washington Hospital Center, Washington, DC 20010 (United States); Waksman, Ron, E-mail: ron.waksman@medstar.net [Division of Interventional Cardiology, MedStar Washington Hospital Center, Washington, DC 20010 (United States)

    2015-04-15

    Objective: The aim of this study was to compare the safety and efficacy of the everolimus-eluting stents (EES) with the paclitaxel-eluting stent (PES) and sirolimus-eluting stent (SES) for the treatment of bare-metal in-stent restenosis. Background: The optimal treatment for bare-metal in-stent restenosis remains controversial. Methods: The study cohort comprised 322 consecutive patients (543 lesions) who presented with bare-metal in-stent restenosis to our institution and underwent coronary artery stent implantation with EES (114 patients; 181 lesions), PES (65 patients; 116 lesions) and SES (143 patients; 246 lesions). The analyzed clinical parameters were the 1-year rates of death, Q-wave myocardial infarction (MI), target lesion revascularization (TLR), target vessel revascularization (TVR), definite stent thrombosis (ST) and major adverse cardiac events (MACE) defined as the composite of death, MI, or TLR at 1-year. Results: The three groups were well matched for the conventional risk factors except for age and chronic kidney disease. The 1-year analyzed clinical parameters were similar in the three groups: death (EES = 3.5%, PES = 4.6%, SES = 4.2%; p = 0.94), MI (EES = 3.5%, PES = 6.3%, SES = 2.1%; p = 0.31), TLR (EES = 9.8%, PES = 9.5%, SES = 5.7%; p = 0.42), TVR (EES = 14.3%, PES = 11.1%, SES = 11.3%; p = 0.74), definite ST (EES = 0.9%, PES = 3.1%, SES = 3.5%; p = 0.38) and MACE (EES = 14.0%, PES = 15.4%, SES = 10.5%; p = 0.54). Male gender (hazard ratio = 0.47; 95% confidence interval = 0.25–0.88) and number of treated lesions (hazard ratio = 1.47; 95% confidence interval = 1.06–2.05) were found to be independent predictors of MACE. Conclusion: The results of the present study indicate that EES may provide similar safety and efficacy as first generation DES for the treatment of patients presenting with bare-metal in-stent restenosis.

  15. Serial 5-Year Evaluation of Side Branches Jailed by Bioresorbable Vascular Scaffolds Using 3-Dimensional Optical Coherence Tomography: Insights From the ABSORB Cohort B Trial (A Clinical Evaluation of the Bioabsorbable Everolimus Eluting Coronary Stent System in the Treatment of Patients With De Novo Native Coronary Artery Lesions).

    Science.gov (United States)

    Onuma, Yoshinobu; Grundeken, Maik J; Nakatani, Shimpei; Asano, Taku; Sotomi, Yohei; Foin, Nicolas; Ng, Jaryl; Okamura, Takayuki; Wykrzykowska, Joanna J; de Winter, Robbert J; van Geuns, Robert-Jan; Koolen, Jacques; Christiansen, Evald; Whitbourn, Robert; McClean, Dougal; Smits, Pieter; Windecker, Stephan; Ormiston, John A; Serruys, Patrick W

    2017-09-01

    The long-term fate of Absorb bioresorbable vascular scaffold (Abbott Vascular, Santa Clara, CA) struts jailing side branch ostia has not been clarified. We therefore evaluate serially (post-procedure and at 6 months, 1, 2, 3, and 5 years) the appearance and fate of jailed Absorb bioresorbable vascular scaffold struts. We performed 3-dimensional optical coherence tomographic analysis of the ABSORB Cohort B trial (A Clinical Evaluation of the Bioabsorbable Everolimus Eluting Coronary Stent System in the Treatment of Patients With De Novo Native Coronary Artery Lesions) up to 5 years using a novel, validated cut-plane analysis method. We included 29 patients with a total of 85 side branch ostia. From the 12 ostia which could be assessed in true serial fashion, 7 showed a pattern of initial decrease in the ostial area free from struts, followed by an increase in strut-free ostial area toward the end of the 5 years of follow-up. In a repeated-measures analysis with time as fixed variable and ostial area free from struts as dependent variable, we showed a numeric decrease in the estimated ostial area free from struts from 0.75 mm 2 (baseline) to 0.68 mm 2 (first follow-up visit at 6 months or 1 year) and 0.63 mm 2 (second follow-up visit at 2 or 3 years). However, from the second visit to the 5-year follow-up visit, there was a statistically significant increase from 0.63 to 0.89 mm 2 ( P =0.001). Struts overlying an ostium divided the ostium into compartments, and the number of these compartments decreased over time. This study showed that in most cases, the side branch ostial area free from struts initially decreased. However, with full scaffold bioresorption, the ostial area free from scaffold increased between 2 to 3 years and 5 years in the vast majority of patients. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00856856. © 2017 American Heart Association, Inc.

  16. A randomized study to compare bioactive titanium stents and everolimus-eluting stents in diabetic patients (TITANIC XV): 1-year results.

    Science.gov (United States)

    López-Mínguez, José R; Nogales-Asensio, Juan M; Doncel-Vecino, Luis J; Merchán-Herrera, Antonio; Pomar-Domingo, Francisco; Martínez-Romero, Pedro; Fernández-Díaz, José A; Valdesuso-Aguilar, Raúl; Moreu-Burgos, José; Díaz-Fernández, José

    2014-07-01

    Up to 25% of patients who undergo a percutaneous coronary intervention show some limitation in the use of drug-eluting stents. The aim of this study was to evaluate if titanium-nitride-oxide-coated stents could be a good alternative to everolimus-eluting stents in diabetic patients. A total of 173 diabetic patients with lesions at moderate risk of restenosis (exclusion criteria: diameter 28 mm in vessels < 3mm, chronic occlusion) were randomized to a titanium group (83 patients) or an everolimus group (90 patients). Baseline characteristics were well balanced; 28.3% of patients were insulin dependent. At 1 year, the incidence of major adverse cardiac events (death, nonfatal myocardial infarction, stroke, or repeat target vessel revascularization) was significantly higher in the titanium group than in the everolimus group (total, 14.5% vs 4.4%; P = .02; noninsulin-dependent subgroup, 9.7% vs 3.2%; P = .14; insulin-dependent subgroup, 28.6% vs 7.1%; P = .04). The incidence of death, nonfatal myocardial infarction, stroke, or any revascularization was 16.9% in the titanium group and 7.8% in the everolimus group (P = .06). Target lesion and vessel revascularizations occurred in 8.4% compared with 3.3% (P = .15) and in 13.3% compared with 3.3% (P = .01) in the titanium and everolimus groups, respectively. Angiographic follow-up at 9 months showed significantly less late lumen loss in the everolimus group (in-segment, 0.52 [standard deviation, 0.58) mm vs -0.05 [0.32] mm; in-stent, 0.76 [0.54] mm vs 0.13 [0.31] mm; P < .0001). The everolimus-eluting stent is superior to the titanium stent for clinical and angiographic end points in diabetic patients with lesions at moderate risk of restenosis. Copyright © 2013 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

  17. Everolimus-eluting bioresorbable stent vs. durable polymer everolimus-eluting metallic stent in patients with ST-segment elevation myocardial infarction

    DEFF Research Database (Denmark)

    Sabaté, Manel; Windecker, Stephan; Iñiguez, Andres

    2015-01-01

    AIMS: Patients with ST-segment elevation myocardial infarction (STEMI) feature thrombus-rich lesions with large necrotic core, which are usually associated with delayed arterial healing and impaired stent-related outcomes. The use of bioresorbable vascular scaffolds (Absorb) has the potential...... to overcome these limitations owing to restoration of native vessel lumen and physiology at long term. The purpose of this randomized trial was to compare the arterial healing response at short term, as a surrogate for safety and efficacy, between the Absorb and the metallic everolimus-eluting stent (EES...... was the 6-month optical frequency domain imaging healing score (HS) based on the presence of uncovered and/or malapposed stent struts and intraluminal filling defects. Main secondary endpoint included the device-oriented composite endpoint (DOCE) according to the Academic Research Consortium definition...

  18. TIDES-ACS Trial: comparison of titanium-nitride-oxide coated bio-active-stent to the drug (everolimus)-eluting stent in acute coronary syndrome. Study design and objectives.

    Science.gov (United States)

    Colkesen, E B; Eefting, F D; Rensing, B J; Suttorp, M J; Ten Berg, J M; Karjalainen, P P; Van Der Heyden, J A

    2015-02-01

    Drug-eluting stents (DES), delivering antiproliferative drugs from a durable polymer, have shown to reduce in-stent restenosis after percutaneous coronary intervention (PCI) compared to bare-metal stents (BMS). However, they have been associated with a hypersensitivity reaction, delayed healing, and incomplete endothelialization, which may contribute to an increased risk of late stent thrombosis. Consequently, a prolonged duration of dual antiplatelet therapy (DAPT) is needed, with an increased risk of bleeding complication. A number of stent technologies are being developed in an attempt to modify late thrombotic events and DAPT duration. The Optimax™ stent is such a novel, next generation bioactive stent (BAS), in which a thicker layer of titanium-nitride-oxide coating is inserted over the stent struts. The rationale of this is to obtain more efficient and rapid vascular healing at the site of the stent implantation. The aim of TIDES-ACS Trial is to compare clinical outcome in patients presenting with ACS, treated with PCI using Optimax-BAS versus Synergy™-EES. Second objective is to explore whether the Optimax™-BAS use is superior compared with Synergy™-EES use with respect of hard end points (cardiac death, myocardial infarction [MI] and major bleeding). A prospective, randomized, multicenter trial (ClinicalTrials.gov Identifier: NCT02049229), will be conducted in interventional centres in Finland (six centres), France (five centres) and Holland (two centres), including a total of 1800 patients.

  19. Vascular Response of the Segments Adjacent to the Proximal and Distal Edges of the ABSORB Everolimus-Eluting Bioresorbable Vascular Scaffold

    DEFF Research Database (Denmark)

    Gogas, Bill D; Serruys, Patrick W; Diletti, Roberto

    2012-01-01

    This study sought to investigate in vivo the vascular response at the proximal and distal edges of the second-generation ABSORB everolimus-eluting bioresorbable vascular scaffold (BVS).......This study sought to investigate in vivo the vascular response at the proximal and distal edges of the second-generation ABSORB everolimus-eluting bioresorbable vascular scaffold (BVS)....

  20. Zotarolimus-eluting vs. sirolimus-eluting coronary stents in patients with and without acute coronary syndromes

    DEFF Research Database (Denmark)

    Thim, Troels; Maeng, Michael; Kaltoft, Anne Kjer

    2012-01-01

    To compare clinical outcomes among patients with acute coronary syndrome treated with zotarolimus-eluting and sirolimus-eluting stents in the SORT OUT III trial.......To compare clinical outcomes among patients with acute coronary syndrome treated with zotarolimus-eluting and sirolimus-eluting stents in the SORT OUT III trial....

  1. Everolimus

    Science.gov (United States)

    ... that last several days; headaches; seizures; confusion; or personality changes.Everolimus may cause a blood clot in ... to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in ...

  2. Comparison of Outcomes in Patients With Versus Without Diabetes Mellitus After Revascularization With Everolimus- and Sirolimus-Eluting Stents (from the SORT OUT IV Trial)

    DEFF Research Database (Denmark)

    Jensen, Lisette Okkels; Thayssen, Per; Junker, Anders

    2012-01-01

    Diabetes is associated with increased risk of major adverse cardiac events (MACEs) after percutaneous coronary intervention. The purpose of this substudy of the SORT OUT IV trial was to compare clinical outcomes in patients with and without diabetes mellitus treated with everolimus-eluting stents...... (EESs) or sirolimus-eluting stents (SESs). In total 2,774 patients (390 with diabetes, 14.1%) were randomized to stent implantation with EESs (n = 1,390, diabetes in 14.0%) or SESs (n = 1,384, diabetes in 14.2%). Randomization was stratified by presence/absence of diabetes. The primary end point...... was MACEs, a composite of cardiac death, myocardial infarction, definite stent thrombosis, or target vessel revascularization within 18 months. MACEs were higher in diabetic than in nondiabetic patients (13.1% vs 6.4%, hazard ratio [HR] 2.08, 95% confidence interval [CI] 1.51 to 2.86). In diabetic patients...

  3. Overtime evaluation of the vascular HEALing process after everolimus-eluting stent implantation by optical coherence tomography. The HEAL-EES study

    Energy Technology Data Exchange (ETDEWEB)

    Otsuki, Shuji; Brugaletta, Salvatore, E-mail: sabrugal@clinic.ub.es; Sabaté, Manel; Shiratori, Yoshitaka; Gomez-Monterrosas, Omar; Scalone, Giancarla; Romero-Villafañe, Sebastian; Hernández-Enríquez, Marco; Freixa, Xavier; Martín-Yuste, Victoria; Masotti, Mónica

    2016-06-15

    Purpose: Second-generation drug-eluting stent (DES) have shown a better safety and efficacy as compared to first generation DES due to an improved vascular healing process. This process has not been so far evaluated in vivo in an overtime fashion by optical coherent tomography (OCT). We sought to evaluate the vascular healing process after everolimus-eluting stent (EES) implantation at 6, 9 and 12 months, by OCT. Methods: Consecutive 36 patients undergoing percutaneous coronary intervention with EES were randomized 1:1:1 to receive OCT imaging at 6 (group A), 9 (group B) or 12-month follow-up (group C). One patient from group C was excluded because of target lesion revascularization at 1-month, whereas 5 patients withdraw the informed consent. Finally, 30 patients were analyzed. Results: Neointimal thickness was not different between 3 groups (group A: 99.50 [94.06–127.79] μm, group B: 107.26 [83.48–133.59] μm, group C: 127.67 [102.51–138.49] μm; p = 0.736). Although the percentage of “uncovered struts” was significantly higher in group A as compared to the other groups (8.0% vs. 4.4% vs. 2.9%, respectively; p = 0.180), the ratio of uncovered to total struts per section < 30% was similar between 3 groups (0.3% vs. 0.3% vs. 0%, respectively; p = 1.000). Conclusion: Healing process following EES implantation seems almost completed at 6-month follow-up. These data, which need to be confirmed in a larger study, may support the decision to shorten dual antiplatelet therapy. - Highlights: • Healing process following everolimus-eluting stent implantation is complete at 6-month • There are no difference in RUTTS > 30% between 6, 9 and 12 months analyses. • This finding may support to shorten dual antiplatelet therapy in this context.

  4. Meta-analysis of Absorb Bioresorbable Vascular Scaffold Versus Cobalt Chromium-everolimus Eluting Stent for Treating the Patients With Coronary Artery Disease%生物可吸收支架与钴铬合金依维莫司洗脱支架治疗冠心病的Meta分析

    Institute of Scientific and Technical Information of China (English)

    庞思; 潘道蓉; 朱灏; 吴文; 蔡金赞; 冒晨昱; 张瑶俊

    2016-01-01

    Objective: To systemically review the safety and efficacy of Absorb bioresorbable vascular scaffold (Absorb BVS) versus cobalt chromium-everolimus eluting stent (CoCr-EES) for treating the patients with coronary artery disease (CAD) by percutaneous coronary intervention (PCI). Methods: We searched relevant literatures in PubMed, Embase, Cochrane Library, CNKI and Wanfang database from 2008-01 to 2015-10, meanwhile, collected published data and randomized controlled trials from meeting abstracts and websites to compare Absorb BVS and CoCr-EES for treating CAD patients. The quality of literatures were assessed and extracted by modiifed Jadad score, Meta-analysis was conducted by STATA 12.0 soft ware. Results: There were 4 eligible trials with 3,389 patients were enrolled. Absorb BVS group, n=2,164 and CoCr-EES group, n=1,225. During the mean of 1.1 years follow-up period, the following incidences were similar between 2 groups:target lesion failure (OR=1.29, 95%CI 0.95-1.74, P=0.10), all cause death (OR=1.31, 95%CI 0.60-2.87, P=0.50), cardiac death (OR=1.38, 95%CI 0.45-4.24, P=0.57), myocardial infarction (OR=1.30, 95%CI 0.93-1.80, P=0.12), deifnite or probable stent thrombosis (OR=2.08, 95%CI 0.95-4.54, P=0.07), re-vascularization (OR=1.03, 95%CI 0.80-1.33, P=0.81), target lesion re-vascularization (OR=1.06, 95%CI 0.67-1.66, P=0.81) and the patient-oriented composite endpoint (OR=0.95, 95%CI 0.66-1.35, P=0.76). Conclusion: Absorb BVS and CoCr-EES had the similar safety and efifcacy for treating the low and moderate risk CAD patients who had angina, ischemia while without symptoms. The longer period of follow-up study and larger randomized, controlled clinical trials were needed for Absorb BVS application in clinical practice.%目的:系统评价Absorb 生物可吸收支架(BVS)对比钴铬合金依维莫司洗脱支架(cobalt chromium-everolimus eluting stent,CoCr-EES)在冠心病介入治疗中的安全性和有效性。  方法:计算机检索Pub

  5. 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

    DEFF Research Database (Denmark)

    Gutiérrez-Chico, Juan Luis; van Geuns, Robert Jan; Regar, Evelyn

    2011-01-01

    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...

  6. Serial optical coherence tomography assessment of malapposed struts after everolimus-eluting stent implantation. A subanalysis from the HEAL-EES study

    Energy Technology Data Exchange (ETDEWEB)

    Ishida, Kohki [Cardiology Department, Cardiovascular Institute, Hospital Clínic, Institut d' Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona (Spain); Otsuki, Shuji [Division of Cardiology, Teikyo University Hospital, Tokyo (Japan); Giacchi, Giuseppe; Ortega-Paz, Luis [Cardiology Department, Cardiovascular Institute, Hospital Clínic, Institut d' Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona (Spain); Shiratori, Yoshitaka [Division of Cardiology, Teikyo University Hospital, Tokyo (Japan); Freixa, Xavier; Martín-Yuste, Victoria; Masotti, Mónica; Sabaté, Manel [Cardiology Department, Cardiovascular Institute, Hospital Clínic, Institut d' Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona (Spain); Brugaletta, Salvatore, E-mail: sabrugal@clinic.ub.es [Cardiology Department, Cardiovascular Institute, Hospital Clínic, Institut d' Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona (Spain)

    2017-01-15

    Background: Incomplete stent apposition (ISA) is related to stent thrombosis, which is a serious adverse event. We aim to assess the time-course of ISA after 2nd generation everolimus-eluting stent (EES) implantation. Methods: In HEAL-EES study, we enrolled 36 patients who underwent percutaneous coronary intervention (PCI) with EES. OCT imaging was performed at baseline and follow-up. Patients were randomized 1:1:1 into 3 groups according to the time in which follow-up was performed: group A (6-month), group B (9-month), and group C (12-month). In this subanalysis, patients who had ISA segments at baseline and/or follow-up OCT were analyzed. Result: At baseline, among 41 lesions in 36 patients, 20 lesions in 18 patients had ISA segments and were analyzed. At baseline, there were 3.0% ISA struts in group A (n = 8), 2.8% in group B (n = 4), and 4.5% in group C (n = 8). At follow-up, ISA struts were present in 0.09%, 0.16% and 0.64%; respectively in groups A, B, and C. At follow-up, there was a significant decrease in the frequency of ISA: group A 3.0% vs. 0.09% (p < 0.001), group B 2.8% vs. 0.16% (p < 0.001), and group C 4.5% vs. 0.64% (p < 0.001). In group A, there was one late acquired ISA at follow-up. Conclusions: In patients undergoing 2nd generation EES implantation, area of acute ISA assessed by OCT, was almost resolved at 6-month follow-up. - Highlights: • Time-course of incomplete stent apposition of everolimus-eluting stent was assessed. • Serial optical coherence tomography images at baseline and follow-up were evaluated. • Acute incomplete stent apposition was almost resolved as early as at 6 months.

  7. The Promus Premier everolimus-eluting platinum chromium stent with durable polymer evaluated in a real world all-comer population in Rotterdam cardiology hospital (the P-SEARCH registry)

    NARCIS (Netherlands)

    Lemmert, M.E.; Mieghem, N.M. van; Geuns, R.J.M. van; Diletti, R.; Bommel, R.J. van; Domburg, R.T. van; Jaegere, P.P. de; Regar, E.; Zijlstra, F.; Boersma, E.; Daemen, J.

    2017-01-01

    BACKGROUND: A new-generation everolimus eluting platinum-chromium stent (EePCS), offering improved radial strength, radiopacity and conformability compared to everolimus-eluting cobalt-chromium stents (EeCCS), was evaluated with regard to safety and efficacy in an all-comer cohort. METHODS: A total

  8. Effects of cobalt-chromium everolimus eluting stents or bare metal stent on fatal and non-fatal cardiovascular events: patient level meta-analysis.

    Science.gov (United States)

    Valgimigli, Marco; Sabaté, Manel; Kaiser, Christoph; Brugaletta, Salvatore; de la Torre Hernandez, Jose Maria; Galatius, Soeren; Cequier, Angel; Eberli, Franz; de Belder, Adam; Serruys, Patrick W; Ferrante, Giuseppe

    2014-11-04

    To examine the safety and effectiveness of cobalt-chromium everolimus eluting stents compared with bare metal stents. Individual patient data meta-analysis of randomised controlled trials. Cox proportional regression models stratified by trial, containing random effects, were used to assess the impact of stent type on outcomes. Hazard ratios with 95% confidence interval for outcomes were reported. Medline, Embase, the Cochrane Central Register of Controlled Trials. Randomised controlled trials that compared cobalt-chromium everolimus eluting stents with bare metal stents were selected. The principal investigators whose trials met the inclusion criteria provided data for individual patients. The primary outcome was cardiac mortality. Secondary endpoints were myocardial infarction, definite stent thrombosis, definite or probable stent thrombosis, target vessel revascularisation, and all cause death. The search yielded five randomised controlled trials, comprising 4896 participants. Compared with patients receiving bare metal stents, participants receiving cobalt-chromium everolimus eluting stents had a significant reduction of cardiac mortality (hazard ratio 0.67, 95% confidence interval 0.49 to 0.91; P=0.01), myocardial infarction (0.71, 0.55 to 0.92; P=0.01), definite stent thrombosis (0.41, 0.22 to 0.76; P=0.005), definite or probable stent thrombosis (0.48, 0.31 to 0.73; Pstents the use of cobalt-chromium everolimus eluting stents improves global cardiovascular outcomes including cardiac survival, myocardial infarction, and overall stent thrombosis. © Valgimigli et al 2014.

  9. Bioresorbable Everolimus-Eluting Vascular Scaffold for Patients With Peripheral Artery Disease (ESPRIT I): 2-Year Clinical and Imaging Results.

    Science.gov (United States)

    Lammer, Johannes; Bosiers, Marc; Deloose, Koen; Schmidt, Andrej; Zeller, Thomas; Wolf, Florian; Lansink, Wouter; Sauguet, Antoine; Vermassen, Frank; Lauwers, Geert; Scheinert, Dierk; Popma, Jeffrey J; McGreevy, Robert; Rapoza, Richard; Schwartz, Lewis B; Jaff, Michael R

    2016-06-13

    This is the first-in-human study of a drug-eluting bioresorbable vascular scaffold (BVS) for treatment of peripheral artery disease (PAD) involving the external iliac artery (EIA) and superficial femoral artery (SFA). Drug-eluting BVS has shown promise in coronary arteries. The ESPRIT BVS system is a device-drug combination consisting of an everolimus-eluting poly-l-lactide scaffold. Safety and performance were evaluated in 35 subjects with symptomatic claudication. Lesions were located in the SFA (88.6%) and EIA (11.4%). Mean lesion length was 35.7 ± 16.0 mm. The study device was successfully deployed in 100% of cases, without recoil. Procedure-related minor complications were observed in 3 patients (groin hematoma, dissection). Within 2 years there was 1 unrelated death, but no patients in this cohort had an amputation. At 1 and 2 years, the binary restenosis rates were 12.1% and 16.1%, respectively, and target lesion revascularization was performed in 3 of 34 patients (8.8%) and 4 of 32 patients (11.8%), respectively. The ankle brachial index 0.75 ± 0.14 improved from pre-procedure to 0.96 ± 0.16 at 2 years' follow-up. At 2 years, 71.0% of the patients were Rutherford-Becker 0, and 93.5% achieved a maximum walking distance of 1,500 feet. The safety of the ESPRIT BVS was demonstrated with no procedure or device-related deaths or amputations within 2 years. The low occurrence of revascularizations was consistent with duplex-ultrasonography showing sustained patency at 2-years. (A Clinical Evaluation of the Abbott Vascular ESPRIT BVS [Bioresorbable Vascular Scaffold] System [ESPRIT I]; NCT01468974). Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  10. Comparison of the Absorbable Polymer Sirolimus-Eluting Stent (MiStent) to the Durable Polymer Everolimus-Eluting Stent (Xience) (from the DESSOLVE I/II and ISAR-TEST-4 Studies).

    Science.gov (United States)

    Lansky, Alexandra J; Kastrati, Adnan; Edelman, Elazer R; Parise, Helen; Ng, Vivian G; Ormiston, John; Wijns, William; Byrne, Robert A

    2016-02-15

    We compared the outcomes of a novel, thin-strut, cobalt-chromium, absorbable, polymer sirolimus-eluting stent (APSES; MiStent) to the durable polymer cobalt-chromium everolimus-eluting stent (EES; Xience). A propensity-matched analysis was performed comparing data from the DES With Sirolimus and a Bioabsorbable Polymer for the Treatment of Patients With De Novo Lesions in the Native Coronary Arteries (DESSOLVE) I and II studies, evaluating the APSES to the EES arm of the Intracoronary Stenting and Angiographic Results: Test Efficacy of 3 Limus-Eluting Stents-4 study. Target lesion failure (TLF) and its components were evaluated at 12 months and annually to 3 years; 805 patients (APSES = 153; EES = 652) were included with propensity matching in 204 patients (APSES = 102; EES = 102). APSES compared with EES had lower TLF at 1 year (3.0% vs 8.0%, p = 0.12) driven by a difference in target lesion revascularization (TLR; 1% vs 6%, p = 0.05), with no difference in target vessel myocardial infarction (p = 0.56) or stent thrombosis (p = 0.31). At 3 years, TLF (5.0% vs 12.5%, p = 0.07) and TLR (2.0% vs 8.4%, p = 0.04) remained lower with APSES. By landmark analysis, there was no significant difference in TLF between 1 and 3 years (p = 0.36). In conclusion, in a propensity-matched analysis, the APSES demonstrated reduced clinically indicated TLR rates at 1 and 3 years compared with the durable polymer EES, with minimal accrual of events between 1 and 3 years. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Drug-eluting stents for acute coronary syndrome: a meta-analysis of randomized controlled trials.

    Directory of Open Access Journals (Sweden)

    Lishan Wang

    Full Text Available Drug-eluting stents (DES are increasingly used for treatment of acute coronary syndrome (ACS. However, clinical efficacy and safety of various types of DES is not well established in these subjects. We therefore evaluated clinical utility of second-generation and first-generation DES in patients with ACS by conducting a meta-analysis.A search of Medline, Embase, the Cochrane databases, and Web of Science was made. Randomized controlled trials (RCTs which compared second-generation DES (everolimus-eluting stents [EES] or zotarolimus-eluting stents [ZES] versus first-generation DES (sirolimus-eluting stents [SES] or paclitaxe-eluting stents [PES] in patients with ACS and provided data on clinical efficacy or safety endpoints were included. Pooled estimates were calculated using random-effects model.A total of 2,757 participants with ACS in 6 RCTs were included. Compared with first-generation one, second-generation DES trended to be associated with the decreased incidence of definite or probable stent thrombosis in ACS patients (risk ratio [RR]  = 0.60, 95% confidence intervals [CI] 0.33 to 1.07, p = 0.09. However, the rate of target lesion revascularization (TLR significantly increased in second-generation DES (RR = 2.08, 95%CI 1.25 to 3.47, p = 0.005. There were no significant differences in the incidence of major adverse cardiac events (MACEs, all-cause death, cardiac death, and recurrent myocardial infarction between the two arms (all p>0.10. The second-generation EES showed a tendency towards lower risk of MACEs (p = 0.06 and a beneficial effect on reducing stent thrombosis episodes (p = 0.009, while the second-generation ZES presented an increased occurrence of MACEs (p = 0.02 and TLR (p = 0.003.Second-generation DES, especially EES, appeared to present a lower risk of stent thrombosis, whereas second-generation ZES might increase the need for repeat revascularization in ACS patients. During coronary

  12. Quality-of-Life After Everolimus-Eluting Stents or Bypass Surgery for Left-Main Disease: Results From the EXCEL Trial.

    Science.gov (United States)

    Baron, Suzanne J; Chinnakondepalli, Khaja; Magnuson, Elizabeth A; Kandzari, David E; Puskas, John D; Ben-Yehuda, Ori; van Es, Gerrit-Anne; Taggart, David P; Morice, Marie-Claude; Lembo, Nicholas J; Brown, W Morris; Banning, Adrian; Simonton, Charles A; Kappetein, A Pieter; Sabik, Joseph F; Serruys, Patrick W; Stone, Gregg W; Cohen, David J

    2017-12-26

    The EXCEL (Evaluation of Xience Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) trial compared outcomes in patients with unprotected left main coronary artery disease (LMCAD) treated with coronary artery bypass graft (CABG) or percutaneous coronary intervention (PCI) using everolimus-eluting stents. Whereas rates of death, stroke, and myocardial infarction were similar at 36 months, event timing and repeat revascularization rates differed by treatment group. To understand the effects of revascularization strategy from the patient's perspective, a prospective quality of life (QoL) substudy was performed alongside the EXCEL trial. Between September 2010 and March 2014, 1,905 patients with LMCAD were randomized to undergo CABG or PCI, of whom 1,788 participated in the QoL substudy. QoL was assessed at baseline and 1, 12, and 36 months using the Seattle Angina Questionnaire, the 12-Item Short Form Health Survey, the Rose Dyspnea Scale, the Patient Health Questionnaire-8, and the EQ-5D. Differences between PCI and CABG were assessed using longitudinal random-effect growth curve models. Over 36 months, both PCI and CABG were associated with significant improvements in QoL compared with baseline. At 1 month, PCI was associated with better QoL than CABG. By 12 months though, these differences were largely attenuated, and by 36 months, there were no significant QoL differences between PCI and CABG. Among selected patients with LMCAD, both PCI and CABG result in similar QoL improvement through 36 months, although a greater early benefit is seen with PCI. Taken together with the 3-year clinical results of EXCEL, these findings suggest that PCI and CABG provide similar intermediate-term outcomes for patients with LMCAD. (Evaluation of Xience Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization [EXCEL]; NCT01205776). Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier

  13. Comparison of Durable-Polymer Zotarolimus-Eluting and Biodegradable-Polymer Biolimus-Eluting Coronary Stents in Patients With Coronary Artery Disease

    DEFF Research Database (Denmark)

    Raungaard, Bent; Christiansen, Evald H; Bøtker, Hans Erik

    2017-01-01

    artery disease or acute coronary syndromes and at least 1 coronary artery lesion requiring treatment with a drug-eluting stent. Endpoints included major adverse cardiac events (MACE), a composite of safety (cardiac death and myocardial infarction not clearly attributable to a non-target lesion......OBJECTIVES: The authors sought to compare the safety and efficacy of the biocompatible durable-polymer zotarolimus-eluting stent with the biodegradable-polymer biolimus-eluting stent in unselected coronary patients. BACKGROUND: Biodegradable-polymer biolimus-eluting stents are superior to first......-generation durable-polymer drug-eluting stents in long-term randomized all-comer trials. Long-term data comparing them to second-generation durable-polymer drug-eluting stents are lacking. METHODS: The study was a randomized, multicenter, all-comer, noninferiority trial in patients with chronic stable coronary...

  14. Optical coherence tomography findings after chronic total occlusion interventions: Insights from the “AngiographiC evaluation of the everolimus-eluting stent in chronic Total occlusions” (ACE-CTO) study (NCT01012869)

    Energy Technology Data Exchange (ETDEWEB)

    Sherbet, Daniel P.; Christopoulos, Georgios; Karatasakis, Aris; Danek, Barbara Anna; Kotsia, Anna; Navara, Rachita; Michael, Tesfaldet T.; Roesle, Michele; Rangan, Bavana V.; Haagen, Donald [VA North Texas Healthcare System and University of Texas Southwestern Medical Center, Dallas, TX (United States); Garcia, Santiago [Minneapolis VA Healthcare System and University of Minnesota, Minneapolis, MN (United States); Maniu, Calin [Bon Secours Health System, Suffolk, VA (United States); Pershad, Ashish [Banner Good Samaritan Medical Center, Phoenix, AZ (United States); Abdullah, Shuaib M.; Hastings, Jeffrey L.; Kumbhani, Dharam J.; Luna, Michael; Addo, Tayo; Banerjee, Subhash [VA North Texas Healthcare System and University of Texas Southwestern Medical Center, Dallas, TX (United States); Brilakis, Emmanouil S., E-mail: esbrilakis@gmail.com [VA North Texas Healthcare System and University of Texas Southwestern Medical Center, Dallas, TX (United States)

    2016-10-15

    Background: There is limited information on optical coherence tomography (OCT) findings after percutaneous coronary intervention (PCI) of chronic total occlusions (CTOs). OCT allows high resolution imaging that can enhance understanding of the vascular response after stenting of chronically occluded vessels. Methods: The Angiographic Evaluation of the Everolimus-Eluting Stent in Chronic Total Occlusions (ACE-CTO) study collected angiographic and clinical outcomes from 100 patients undergoing CTO PCI with the everolimus-eluting stent (EES). OCT was performed 8-months post stenting in 62 patients. Every third frame was analyzed throughout the course of the stented arterial segment. Lumen contours were semi-automatically traced and stent struts were manually delineated, with automatic measurement of the strut to lumen distance. Struts on the luminal side of the lumen contour were classified as malapposed if the distance to the lumen contour exceeded 0.108 mm. Results: A total of 44,450 struts in 6047 frames were analyzed, of which 4113 9.3%, 95% confidence intervals [CI] 9.0% to 9.5%) were malapposed and 1230 (2.8%, 95% CI 2.6% to 2.9%) were uncovered. Fifty-five of 62 patients (88.7%, 95% CI 78.5% to 98.4%) had at least one malapposed stent strut and 50 patients (80.7%, 95% CI 69.2% to 88.6%) had at least one uncovered stent strut. Mean strut-intimal thickness of the apposed and malapposed struts was 0.126 ± 0.140 mm and − 0.491 ± 0.440 mm, respectively. Conclusion: High rates of stent strut malapposition and incomplete stent strut coverage were observed after CTO PCI using EES, highlighting unique challenges associated with stent implantation in CTOs. - Highlights: • Percutaneous coronary intervention with drug-eluting stents for chronic total occlusion is associated with a 40% rate of binary in-stent restenosis at 8 months • Of patients who receive a drug eluting stent for a chronic total occlusion 88.7% will have stent strut malapposition and 80.7% will

  15. Risk and timing of clinical events according to diabetic status of patients treated with everolimus-eluting bioresorbable vascular scaffolds versus everolimus-eluting stent: 2-year results from a propensity score matched comparison of ABSORB EXTEND and SPIRIT trials.

    Science.gov (United States)

    Campos, Carlos M; Caixeta, Adriano; Franken, Marcelo; Bartorelli, Antonio L; Whitbourn, Robert J; Wu, Chiung-Jen; Li Paul Kao, Hsien; Rosli, Mohd Ali; Carrie, Didier; De Bruyne, Bernard; Stone, Gregg W; Serruys, Patrick W; Abizaid, Alexandre

    2018-02-15

    to compare the occurrence of clinical events in diabetics treated with the Absorb bioresorbable vascular scaffold (Absorb BVS; Abbott Vascular, Santa Clara, CA) versus everolimus-eluting metal stents (EES; XIENCE V; Abbott Vascular, Santa Clara, CA) BACKGROUND: There are limited data dedicated to clinical outcomes of diabetic patients treated with bioresorbable scaffolds (BRS) at 2-year horizon. The present study included 812 patients in the ABSORB EXTEND study in which a total of 215 diabetic patients were treated with Absorb BVS. In addition, 882 diabetic patients treated with EES in pooled data from the SPIRIT clinical program (SPIRIT II, SPIRIT III and SPIRIT IV trials) were used for comparison by applying propensity score matching using 29 different variables. The primary endpoint was ischemia driven major adverse cardiac events (ID-MACE), including cardiac death, myocardial infarction (MI), and ischemia driven target lesion revascularization (ID-TLR). After 2 years, the ID-MACE rate was 6.5% in the Absorb BVS vs. 8.9% in the Xience group (P = 0.40). There was no difference for MACE components or definite/probable device thrombosis (HR: 1.43 [0.24,8.58]; P = 0.69). The occurrence of MACE was not different for both diabetic status (insulin- and non-insulin-requiring diabetes) in all time points up to the 2-year follow-up for the Absorb and Xience groups. In this largest ever patient-level pooled comparison on the treatment of diabetic patients with BRS out to two years, individuals with diabetes treated with the Absorb BVS had a similar rate of MACE as compared with diabetics treated with the Xience EES. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  16. Effects of cobalt-chromium everolimus eluting stents or bare metal stent on fatal and non-fatal cardiovascular events

    DEFF Research Database (Denmark)

    Valgimigli, Marco; Sabaté, Manel; Kaiser, Christoph

    2014-01-01

    eluting stents with bare metal stents were selected. The principal investigators whose trials met the inclusion criteria provided data for individual patients. PRIMARY OUTCOMES: The primary outcome was cardiac mortality. Secondary endpoints were myocardial infarction, definite stent thrombosis, definite...... a significant reduction of cardiac mortality (hazard ratio 0.67, 95% confidence interval 0.49 to 0.91; P=0.01), myocardial infarction (0.71, 0.55 to 0.92; P=0.01), definite stent thrombosis (0.41, 0.22 to 0.76; P=0.005), definite or probable stent thrombosis (0.48, 0.31 to 0.73; P... coronary syndrome v stable coronary artery disease), diabetes mellitus, female sex, use of glycoprotein IIb/IIIa inhibitors, and up to one year v longer duration treatment with dual antiplatelets. CONCLUSIONS: This meta-analysis offers evidence that compared with bare metal stents the use of cobalt...

  17. Efficacy and Safety of the Absorb Everolimus-Eluting Bioresorbable Scaffold for Treatment of Patients With Diabetes Mellitus: Results of the Absorb Diabetic Substudy.

    Science.gov (United States)

    Kereiakes, Dean J; Ellis, Stephen G; Kimura, Takeshi; Abizaid, Alexandre; Zhao, Weiying; Veldhof, Susan; Vu, Minh-Thien; Zhang, Zhen; Onuma, Yoshinobu; Chevalier, Bernard; Serruys, Patrick W; Stone, Gregg W

    2017-01-09

    The study sought to evaluate the efficacy and safety of the Absorb everolimus-eluting bioresorbable vascular scaffold (BVS) (Abbott Vascular, Abbott Park, Illinois) in patients with diabetes mellitus. Randomized, controlled trials have demonstrated comparable clinical outcomes following percutaneous coronary intervention with either Absorb BVS or metallic Xience everolimus-eluting stent. However, these trials lack power required to provide reliable treatment effect estimates in this high-risk population. In a pre-specified, powered analysis, patients with diabetes who received ≥1 Absorb were pooled from the ABSORB II, III, and JAPAN randomized trials and from the single arm ABSORB EXTEND registry. The study composite primary endpoint was target lesion failure (TLF) at 1 year following Absorb BVS compared with a performance goal of 12.7%. Among 754 diabetic patients included in analysis (27.3% insulin treated), the 1-year TLF rate was 8.3% (upper 1-sided 95% confidence limit: 10.1%; p = 0.0001 vs. performance goal). Scaffold thrombosis (definite or probable) was observed in 2.3% of patients. Multivariable regression identified older age, insulin treatment, and smaller pre-procedure reference vessel diameter as significant independent predictors of 1-year TLF. The Absorb diabetic substudy suggests efficacy and safety of the Absorb BVS for treatment of patients with diabetes mellitus. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  18. Patient-rated health status predicts prognosis following percutaneous coronary intervention with drug-eluting stenting

    DEFF Research Database (Denmark)

    Pedersen, Susanne S.; Versteeg, Henneke; Denollet, Johan

    2011-01-01

    In patients treated with percutaneous coronary intervention (PCI) with the paclitaxel-eluting stent, we examined whether patient-rated health status predicts adverse clinical events.......In patients treated with percutaneous coronary intervention (PCI) with the paclitaxel-eluting stent, we examined whether patient-rated health status predicts adverse clinical events....

  19. First-in-man study of simvastatin-eluting stent in de novo coronary lesions: the SIMVASTENT study.

    Science.gov (United States)

    Zago, Alexandre C; Matte, Bruno S; Reginato, Luciana; Iturry-Yamamoto, Germán; Krepsky, Ana; Bergoli, Luiz Carlos C; Balvedi, Julise; Raudales, José C; Saadi, Eduardo K; Zago, Alcides J

    2012-01-01

    Statins have anti-inflammatory and antiproliferative properties irrespective of their cholesterol-lowering effects. The aim of the present study was to evaluate a simvastatin-eluting stent (SimvES) in the treatment of de novo coronary lesions. Forty-two patients with de novo coronary artery lesions were assigned to SimvES, bare-metal stent (BMS) or everolimus-eluting stent (EES) implantation followed by intravascular ultrasound (IVUS) for neointimal quantitative analysis. Six months later, quantitative coronary angiography (QCA) and IVUS were repeated. QCA showed no binary restenosis, a mean in-stent late loss of 1.05 ± 0.25 mm (BMS, 1.12 ± 0.48 mm; EES, 0.20 ± 0.16 mm) and a diameter stenosis of 33.5 ± 7.1% (BMS, 35.5 ± 15.30%; EES, 7.2 ± 3.12%). Control IVUS showed a mean in-stent obstruction of 18.3 ± 9.4% (BMS, 32.8 ± 19.1%; EES, 9.8 ± 2.4%) and a neointimal volume index of 1.58 ± 0.75 mm(3)/mm (BMS, 2.93 ± 1.76 mm(3)/mm; EES, 0.80 ± 0.16 mm(3)/mm). Thrombus, late incomplete apposition and major adverse cardiac events were not observed. In this sample of patients with de novo coronary lesions, the use of a SimvES was not related to major adverse cardiac events, but it was associated with a higher level of neointimal proliferation than expected.

  20. Outcome of everolimus eluting bioabsorbable vascular scaffold (BVS) compared to non BVS drug eluting stent in the management of ST-segment elevation myocardial infarction (STEMI) — A comparative study

    Energy Technology Data Exchange (ETDEWEB)

    Chakraborty, Rabin; Patra, Soumya, E-mail: dr_soumyapatra@rediffmail.com; Banerjee, Suvro; Pande, Arindam; Khan, Aftab; Mandol, Prakash Chandra; Ghosh, Debashish; De, Swapan Kumar; Das, Sankha Subhro; Nag, Raja

    2016-04-15

    Background: The safety and efficacy of everolimus eluting bioabsorbable vascular scaffold (BVS) in the management of “ST” segment elevation myocardial infarction (STEMI) are yet to be established. Aims: To evaluate immediate and short term safety and efficacy of the everolimus-eluting ABSORB BVS compared with non BVS drug eluting stent (DES) in patients with STEMI. Methods: From December 2013 to December 2014, 220 patients with STEMI were included in this study. Among them, 35 patients treated with BVS were compared with a control group composed of 180 patients who underwent non BVS DES implantation in the same time period. The incidence of major adverse cardiac events (MACE: stent thrombosis: death, non-fatal myocardial infarction, or target vessel/lesion revascularization) before discharge and up to six months was evaluated. Results: 1 vessel disease was more frequent whereas, 2 and 3 vessel disease was less frequent in BVS group. Procedural characteristics were also similar between groups, except for the use of post dilation (p = 0.04). Procedural success, in-hospital, and up to six-month MACE rates were similar between both groups. Definite or probable stent thrombosis did not occur (according to the ARC criteria) in BVS patients, though two patients during the index admission and another two patients in the first month after DES implantation had stent thrombosis. Conclusion: The use of the ABSORB BVS for STEMI is feasible and associated with good procedural safety, and angiographic success rate.

  1. Outcome of everolimus eluting bioabsorbable vascular scaffold (BVS) compared to non BVS drug eluting stent in the management of ST-segment elevation myocardial infarction (STEMI) — A comparative study

    International Nuclear Information System (INIS)

    Chakraborty, Rabin; Patra, Soumya; Banerjee, Suvro; Pande, Arindam; Khan, Aftab; Mandol, Prakash Chandra; Ghosh, Debashish; De, Swapan Kumar; Das, Sankha Subhro; Nag, Raja

    2016-01-01

    Background: The safety and efficacy of everolimus eluting bioabsorbable vascular scaffold (BVS) in the management of “ST” segment elevation myocardial infarction (STEMI) are yet to be established. Aims: To evaluate immediate and short term safety and efficacy of the everolimus-eluting ABSORB BVS compared with non BVS drug eluting stent (DES) in patients with STEMI. Methods: From December 2013 to December 2014, 220 patients with STEMI were included in this study. Among them, 35 patients treated with BVS were compared with a control group composed of 180 patients who underwent non BVS DES implantation in the same time period. The incidence of major adverse cardiac events (MACE: stent thrombosis: death, non-fatal myocardial infarction, or target vessel/lesion revascularization) before discharge and up to six months was evaluated. Results: 1 vessel disease was more frequent whereas, 2 and 3 vessel disease was less frequent in BVS group. Procedural characteristics were also similar between groups, except for the use of post dilation (p = 0.04). Procedural success, in-hospital, and up to six-month MACE rates were similar between both groups. Definite or probable stent thrombosis did not occur (according to the ARC criteria) in BVS patients, though two patients during the index admission and another two patients in the first month after DES implantation had stent thrombosis. Conclusion: The use of the ABSORB BVS for STEMI is feasible and associated with good procedural safety, and angiographic success rate.

  2. Long-Term Results of Everolimus-Eluting Stents Versus Drug-Eluting Balloons in Patients With Bare-Metal In-Stent Restenosis: 3-Year Follow-Up of the RIBS V Clinical Trial.

    Science.gov (United States)

    Alfonso, Fernando; Pérez-Vizcayno, María José; García Del Blanco, Bruno; Otaegui, Imanol; Masotti, Mónica; Zueco, Javier; Veláquez, Maite; Sanchís, Juan; García-Touchard, Arturo; Lázaro-García, Rosa; Moreu, José; Bethencourt, Armando; Cuesta, Javier; Rivero, Fernando; Cárdenas, Alberto; Gonzalo, Nieves; Jiménez-Quevedo, Pilar; Fernández, Cristina

    2016-06-27

    The aim of this study was to compare the long-term efficacy of everolimus-eluting stents (EES) and drug-eluting balloons (DEB) in patients with bare-metal stent in-stent restenosis (ISR). The relative long-term clinical efficacy of current therapeutic modalities in patients with ISR remains unknown. The 3-year clinical follow-up (pre-specified endpoint) of patients included in the RIBS V (Restenosis Intra-Stent of Bare-Metal Stents: Drug-Eluting Balloon vs Everolimus-Eluting Stent Implantation) randomized clinical trial was analyzed. All patients were followed yearly using a pre-defined structured questionnaire. A total of 189 patients with bare-metal stent ISR were allocated to either EES (n = 94) or DEB (n = 95). Clinical follow-up at 1, 2, and 3 years was obtained in all patients (100%). Compared with patients treated with DEB, those treated with EES obtained better angiographic results, including larger minimal luminal diameter at follow-up (primary study endpoint; 2.36 ± 0.6 mm vs. 2.01 ± 0.6 mm; p 1 year) target vessel (3 [3.2%] vs. 3 [3.2%]; p = 0.95) and target lesion (1 [1%] vs. 2 [2.1%]; p = 0.54) revascularization was low and similar in the 2 arms. Rates of definite or probable stent thrombosis (1% vs. 0%) were also similar in the 2 arms. The 3-year clinical follow-up of the RIBS V clinical trial confirms the sustained safety and efficacy of EES and DEB in patients treated for bare-metal stent ISR. In this setting, EES reduce the need for target lesion revascularization at very long-term follow-up. (RIBS V [Restenosis Intra-Stent of Bare Metal Stents: Paclitaxel-Eluting Balloon vs Everolimus-Eluting Stent] [RIBS V]; NCT01239953). Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  3. Comparing Stent Thrombosis associated with Zotarolimus Eluting Stents versus Everolimus Eluting Stents at 1 year follow up: a systematic review and meta-analysis of 6 randomized controlled trials.

    Science.gov (United States)

    Bundhun, Pravesh Kumar; Yanamala, Chandra Mouli; Huang, Wei-Qiang

    2017-03-16

    Two thousand fifteen has been a winning year for Drug Eluting Stents (DES). Increase in the number of patients with cardiovascular diseases treated by Percutaneous Coronary Intervention (PCI) has resulted to a high demand for second generation DES. This current analysis aimed to compare the different types of Stent Thrombosis (ST) associated with Zotarolimus Eluting Stents (ZES) versus Everolimus Eluting Stents (EES) at 1 year follow up. Electronic databases were searched for studies comparing ZES with EES. Different types of ST reported at 1 year follow up were considered as the primary endpoints in this analysis. Odds Ratios (OR) with 95% Confidence Intervals (CIs) were used as the statistical parameters and the pooled analyses were carried out by the RevMan 5 · 3 software. A total number of 10,512 patients were included in this analysis. No significant difference in any definite ST, acute definite ST, subacute definite ST, and late definite ST were observed between ZES and EES, at 1 year follow up with OR: 1.70, 95% CI: 0.92 - 3.16; P = 0.09, OR: 3.44, 95% CI: 0.82 - 14.43; P = 0.09, OR: 1.13, 95% CI: 0.43 - 2.95; P = 0.80 and OR: 2.39, 95% CI: 0.83 - 6.85; P = 0.11 respectively. Moreover, any definite or probable ST and definite/probable/possible ST were also not significantly different with OR: 1.39, 95% CI: 0.89 - 2.17; P = 0.15 and OR: 1.19, 95% CI: 0.84 - 1.70; P = 0.33 respectively. In addition, any probable ST, acute probable ST, late probable ST and possible ST were also not significantly different at 1 year follow up with OR: 1.11, 95% CI: 0.60 - 2.05; P = 0.75, OR: 0.53, 95% CI: 0.12 - 2.40; P = 0.41, OR: 1.67, 95% CI: 0.35 - 7.86; P = 0.52 and OR: 1.08, 95% CI: 0.64 - 1.82; P = 0.78 respectively. At 1 year follow up, ZES were not associated with significantly lower or higher definite and probable ST compared to EES. In addition, no significant difference was observed in acute, subacute and late

  4. Efficacy and safety of zotarolimus-eluting and sirolimus-eluting coronary stents in routine clinical care (SORT OUT III): a randomised controlled superiority trial

    DEFF Research Database (Denmark)

    Rasmussen, Klaus; Maeng, Michael; Kaltoft, Anne

    2010-01-01

    In low-risk patients, the zotarolimus-eluting stent has been shown to reduce rates of restenosis without increasing the risk of stent thrombosis. We compared the efficacy and safety of the zotarolimus-eluting stent versus the sirolimus-eluting stent in patients with coronary artery disease who we...

  5. In-stent neoatherosclerosis and tissue characteristics of restenotic lesions following implantation of second generation drug-eluting stents in unrestricted coronary lesions: Optical frequency domain imaging study.

    Science.gov (United States)

    Sabbah, Mahmoud; Kadota, Kazushige; El-Eraky, Azza; Kamal, Hanan M; Abdellah, Ahmed-Tageldien; El Hawary, Ahmed

    2017-06-01

    Differences in stent platform, polymer coatings, and antirestenotic drugs among the current in use second-generation drug-eluting stents (G2-DESs) may induce significant variations in neointimal response and vascular healing, which may impact the prevalence of neoatherosclerosis (NA) and morphological appearance of the restenotic tissue. Utilizing Optical frequency domain imaging, two independent reviewers, retrospectively compared the prevalence of neoatherosclerosis (NA), and the morphological differences, and tissue characteristics of 50 G2-DESs in-stent restenosis (ISR) lesions (35 everolimus-eluting stent [22 cobalt-chromium (CoCr), 13 platinum-chromium (PtCr)], and 15 biolimus-eluting stent [BES]) implanted liberally in unrestricted coronary lesions. More than half of the stents were implanted in type C lesions, while 40% of the stents were implanted primarily in lesions with recanalized chronic total occlusion. NA, defined as a neointima formation with the presence of lipids or calcification, was observed in fewer than half (24/50) of all ISR lesions with no significant in-between group differences (41%, 69%, and 40% in CoCr, PtCr, and BES respectively, P = 0.22), nor were there any significant differences in the morphological appearance or tissue characteristics between all G2-DESs subtypes. Acknowledging some limitations, our results may suggest that the prevalence of NA and the morphological appearance of restenotic lesions might not differ when G2-DESs are implanted in unrestricted, rather complex, coronary lesions. © 2017, Wiley Periodicals, Inc.

  6. Correlates and Impact of Coronary Artery Calcifications in Women Undergoing Percutaneous Coronary Intervention With Drug-Eluting Stents

    DEFF Research Database (Denmark)

    Giustino, Gennaro; Mastoris, Ioannis; Baber, Usman

    2016-01-01

    OBJECTIVES: The aim of this study was to investigate the clinical correlates and prognostic impact of coronary artery calcification (CAC) in women undergoing percutaneous coronary intervention with drug-eluting stents (DES). BACKGROUND: The clinical correlates and the prognostic significance of CAC...

  7. First-Generation Versus Second-Generation Drug-Eluting Stents in Coronary Chronic Total Occlusions: Two-Year Results of a Multicenter Registry.

    Directory of Open Access Journals (Sweden)

    Jong-Hwa Ahn

    Full Text Available Limited data are available regarding the long-term clinical outcomes of second-generation drug-eluting stents (DES versus first-generation DES in patients with coronary chronic total occlusion (CTO who undergo percutaneous coronary intervention (PCI. The aim of this study was to compare the clinical outcomes of second-generation DES with those of first-generation DES for the treatment of CTO.Between March 2003 and February 2012, 1,006 consecutive patients with CTO who underwent successful PCI using either first-generation DES (n = 557 or second-generation DES (n = 449 were enrolled in a multicenter, observational registry. Propensity-score matching was also performed. The primary outcome was cardiac death over a 2-year follow-up period. No significant differences were observed between the two groups regarding the incidence of cardiac death (first-generation DES versus second-generation DES; 2.5% vs 2.0%; hazard ratio [HR]: 0.86; 95% confidence interval [CI]: 0.37 to 1.98; p = 0.72 or major adverse cardiac events (MACE, 11.8% vs 11.4%; HR: 1.00; 95% CI: 0.67 to 1.50; p = 0.99. After propensity score matching, the incidences of cardiac death (HR: 0.86; 95% CI: 0.35 to 2.06; p = 0.86 and MACE (HR: 0.93; 95% CI: 0.63 to 1.37; p = 0.71 were still similar in both groups. Furthermore, no significant differences were observed between sirolimus-eluting, paclitaxel-eluting, zotarolimus-eluting, and everolimus-eluting stents regarding the incidence of cardiac death or MACE.This study shows that the efficacy of second-generation DES is comparable to that of first-generation DES for treatment of CTO over 2 years of follow-up.

  8. Everolimus: a proliferation signal inhibitor with clinical applications in organ transplantation, oncology, and cardiology.

    Science.gov (United States)

    Gabardi, Steven; Baroletti, Steven A

    2010-10-01

    Everolimus, a proliferation signal inhibitor in the mammalian target of rapamycin (mTOR) drug class, has many clinical applications, including in organ transplantation, oncology, and cardiology. It currently has United States Food and Drug Administration (FDA) approval for prophylaxis against rejection in de novo renal transplant recipients, treatment of renal cell carcinoma, and use as a drug-eluting stent. To review the pharmacology, pharmacokinetics, efficacy, and safety of everolimus, we performed a search of the MEDLINE database (January 1997-April 2010) for all English-language articles of in vitro and in vivo studies that evaluated everolimus, as well as abstracts from recent scientific meetings and the manufacturer. In transplantation, everolimus demonstrates immunosuppressive properties and has been used to prevent acute rejection in cardiac, liver, lung, and renal transplant recipients. It appears that this agent may be potent enough to allow for the minimization or removal of calcineurin inhibitors in the long-term management of renal transplant recipients. In oncology, everolimus has been proven effective for the management of treatment-resistant renal cell carcinoma. In cardiology, everolimus is available as a drug-coated stent and is used in percutaneous coronary interventions for prevention of restenosis. In transplant recipients and patients with renal cell carcinoma, everolimus appears to have an extensive adverse-event profile. The pharmacologic properties of everolimus differentiate this agent from other drugs used in these clinical areas, and its pharmacokinetic properties differentiate it from sirolimus.

  9. The stenting strategy of drug-eluting stents for coronary artery disease in patients on dialysis

    Directory of Open Access Journals (Sweden)

    Hiroshi Fujita

    2014-12-01

    Full Text Available Background: Reports regarding the relationship between the length and diameter of implanted drug-eluting stents and clinical and angiographic outcomes in dialysis patients are limited. Aim: We investigated the efficiency of drug-eluting stents for coronary artery disease in patients on dialysis from the viewpoint of stent sizing. Methods: Sirolimus-eluting stents were implanted in 88 lesions and bare metal stents were implanted in 43 lesions. We compared stenting strategy, major adverse cardiac events, and angiographic results between sirolimus-eluting stent and bare metal stent groups. Results: Stent diameter was smaller and stent length was longer in the sirolimus-eluting stent group than in the bare metal stent group in our routine practices. There was no significant between-group difference in late diameter loss. Rates of angiographic restenosis and target lesion revascularization were significantly higher in the sirolimus-eluting stent group than in the bare metal stent group. Although stent length was significantly longer and stent diameter was smaller in the sirolimus-eluting stent group, sirolimus-eluting stents did not improve the subsequent clinical and angiographic results compared with bare metal stents in dialysis patients. Conclusion: In dialysis patients, a longer length and/or smaller diameter sirolimus-eluting stent implantation was associated with high rates of restenosis and target lesion revascularization compared with bare metal stents.

  10. Differential clinical outcomes after 1 year versus 5 years in a randomised comparison of zotarolimus-eluting and sirolimus-eluting coronary stents (the SORT OUT III study)

    DEFF Research Database (Denmark)

    Maeng, Michael; Tilsted, Hans Henrik; Jensen, Lisette Okkels

    2014-01-01

    received two different types of drug-eluting stents. METHODS: We undertook this multicentre, open-label, randomised superiority trial at five percutaneous coronary intervention centres in Denmark. We randomly allocated 2332 eligible adult patients (≥18 years of age) with an indication for drug......-eluting stent implantation to the zotarolimus-eluting Endeavor Sprint stent (Medtronic, Santa Rosa, CA, USA) or the sirolimus-eluting Cypher Select Plus stent (Cordis, Johnson & Johnson, Warren, NJ, USA). Randomisation of participants was achieved by computer-generated block randomisation and a telephone...

  11. Zotarolimus-eluting durable-polymer-coated stent versus a biolimus-eluting biodegradable-polymer-coated stent in unselected patients undergoing percutaneous coronary intervention (SORT OUT VI)

    DEFF Research Database (Denmark)

    Raungaard, Bent; Jensen, Lisette Okkels; Tilsted, Hans-Henrik

    2015-01-01

    BACKGROUND: New-generation drug-eluting coronary stents have reduced the risk of coronary events, especially in patients with complex disease or lesions. To what extent different stent platforms, polymers, and antiproliferative drugs affect outcomes, however, is unclear. We investigated the safety...... and efficacy of a third-generation stent by comparing a highly biocompatible durable-polymer-coated zotarolimus-eluting stent with a biodegradable-polymer-coated biolimus-eluting stent. METHODS: This open-label, randomised, multicentre, non-inferiority trial was done at three sites across western Denmark. All......-polymer zotarolimus-eluting stent or the biodegradable-polymer biolimus-eluting stent. The primary endpoint was a composite of safety (cardiac death and myocardial infarction not clearly attributable to a non-target lesion) and efficacy (target-lesion revascularisation) at 12 months, analysed by intention to treat...

  12. Drug-eluting versus bare-metal stents in large coronary arteries

    DEFF Research Database (Denmark)

    Kaiser, Christoph; Galatius, Soeren; Erne, Paul

    2010-01-01

    Recent data have suggested that patients with coronary disease in large arteries are at increased risk for late cardiac events after percutaneous intervention with first-generation drug-eluting stents, as compared with bare-metal stents. We sought to confirm this observation and to assess whether...

  13. Drug-Eluting Balloons in the Treatment of Coronary De Novo Lesions

    DEFF Research Database (Denmark)

    Richelsen, Rasmus Kapalu Broge; Overvad, Thure Filskov; Jensen, Svend Eggert

    2016-01-01

    Drug-eluting balloons (DEBs) have emerged as a new application in percutaneous coronary intervention. DEBs have proven successful in the treatment of in-stent restenosis, but their role in de novo lesions is less clear. This paper provides a review of the current studies where DEBs have been used...

  14. Stent coverage and neointimal proliferation in bare metal stents postdilated with a Paclitaxel-eluting balloon versus everolimus-eluting stents: prospective randomized study using optical coherence tomography at 6-month follow-up.

    Science.gov (United States)

    Poerner, Tudor C; Otto, Sylvia; Gassdorf, Johannes; Nitsche, Kristina; Janiak, Florian; Scheller, Bruno; Goebel, Björn; Jung, Christian; Figulla, Hans R

    2014-12-01

    In this randomized trial, strut coverage and neointimal proliferation of a therapy of bare metal stents (BMSs) postdilated with the paclitaxel drug-eluting balloon (DEB) was compared with everolimus drug-eluting stents (DESs) at 6-month follow-up using optical coherence tomography. We hypothesized sufficient stent coverage at follow-up. A total of 105 lesions in 90 patients were treated with either XIENCE V DES (n=51) or BMS postdilated with the SeQuent Please DEB (n=54). At follow-up, comparable results on the primary optical coherence tomography end point (percentage uncovered struts 5.64±9.65% in BMS+DEB versus 4.93±9.29% in DES; P=0.366) were found. Thus, BMS+DEB achieved the prespecified noninferiority margin of 5% uncovered struts versus DES (difference between treatment means, 0.71%; one-sided upper 95% confidence interval, 4.14%; noninferiority P=0.04). Optical coherence tomography analysis showed significantly more global neointimal proliferation in the BMS+DEB group (15.7±7.8 versus 11.0±5.2 mm(3) proliferation volume/cm stent length; P=0.002). No significant focal in-stent stenosis analyzed with angiography (percentage diameter stenosis at follow-up, 22.8±11.9 versus 16.9±10.4; P=0.014) and optical coherence tomography (peak local area stenosis, 39.5±13.8% versus 36.8±15.6%; P=0.409) was found. Good stent strut coverage of >94% was found in both therapy groups. Despite greater suppression of global neointimal growth in DES, both DES and BMS+DEB effectively prevented clinically relevant focal restenosis at 6-month follow-up. http://www.clinicaltrials.gov. Unique identifier: NCT01056744. © 2014 American Heart Association, Inc.

  15. Efficacy and safety of zotarolimus-eluting and sirolimus-eluting coronary stents in routine clinical care (SORT OUT III): a randomised controlled superiority trial

    DEFF Research Database (Denmark)

    Rasmussen, Klaus; Maeng, Michael; Kaltoft, Anne

    2010-01-01

    BACKGROUND: In low-risk patients, the zotarolimus-eluting stent has been shown to reduce rates of restenosis without increasing the risk of stent thrombosis. We compared the efficacy and safety of the zotarolimus-eluting stent versus the sirolimus-eluting stent in patients with coronary artery...... disease who were receiving routine clinical care with no direct follow-up. METHODS: We did a single-blind, all-comer superiority trial in adult patients with chronic stable coronary artery disease or acute coronary syndromes, and at least one target lesion. Patients were treated at one of five...... Danish administrative and health-care registries. The primary endpoint was a composite of major adverse cardiac events within 9 months: cardiac death, myocardial infarction, and target vessel revascularisation. Intention-to-treat analyses were done at 9-month and 18-month follow-up. This trial...

  16. Coronary Artery Bypass Surgery Versus Drug-Eluting Stent Implantation for Left Main or Multivessel Coronary Artery Disease A Meta-Analysis of Individual Patient Data

    NARCIS (Netherlands)

    Lee, Cheol Whan; Ahn, Jung-Min; Cavalcante, Rafael; Sotomi, Yohei; Onuma, Yoshinobu; Suwannasom, Pannipa; Tenekecioglu, Erhan; Yun, Sung-Cheol; Park, Duk-Woo; Kang, Soo-Jin; Lee, Seung-Whan; Kim, Young-Hak; Park, Seong-Wook; Serruys, Patrick W.; Park, Seung-Jung

    2016-01-01

    OBJECTIVES The authors undertook a patient-level meta-analysis to compare long-term outcomes after coronary artery bypass grafting (CABG) versus percutaneous coronary intervention (PCI) with drug-eluting stents (DES) in 3,280 patients with left main or multivessel coronary artery disease (CAD).

  17. Coronary Artery Bypass Surgery Versus Drug-Eluting Stent Implantation for Left Main or Multivessel Coronary Artery Disease: A Meta-Analysis of Individual Patient Data.

    Science.gov (United States)

    Lee, Cheol Whan; Ahn, Jung-Min; Cavalcante, Rafael; Sotomi, Yohei; Onuma, Yoshinobu; Suwannasom, Pannipa; Tenekecioglu, Erhan; Yun, Sung-Cheol; Park, Duk-Woo; Kang, Soo-Jin; Lee, Seung-Whan; Kim, Young-Hak; Park, Seong-Wook; Serruys, Patrick W; Park, Seung-Jung

    2016-12-26

    The authors undertook a patient-level meta-analysis to compare long-term outcomes after coronary artery bypass grafting (CABG) versus percutaneous coronary intervention (PCI) with drug-eluting stents (DES) in 3,280 patients with left main or multivessel coronary artery disease (CAD). The relative efficacy and safety of CABG versus PCI with DES for left main or multivessel CAD remain controversial. Data were pooled from the BEST (Randomized Comparison of Coronary Artery Bypass Surgery and Everolimus Eluting Stent Implantation in the Treatment of Patients With Multivessel Coronary Artery Disease), PRECOMBAT (Premier of Randomized Comparison of Bypass Surgery vs. Angioplasty Using Sirolimus-Eluting Stent in Patients With Left Main Coronary Artery Disease), and SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) trials. The primary outcome was a composite of all-cause death, myocardial infarction, or stroke. The median follow-up was 60 months, and follow-up was completed for 96.2% of patients. The rate of primary outcome was significantly lower with CABG than with PCI (13.0% vs. 16.0%; hazard ratio [HR]: 0.83; 95% confidence interval [CI]: 0.69 to 1.00; p = 0.046). The difference was mainly driven by reduction in myocardial infarction (HR: 0.46; 95% CI: 0.33 to 0.64; p patients with multivessel CAD (p = 0.001), but no between-group difference in those with left main CAD (p = 0.427). The rates for all-cause death and stroke were similar between the 2 groups. By contrast, the need for repeat revascularization was significantly lower in the CABG group compared with the PCI group. CABG, as compared with PCI with DES, reduced long-term rates of the composite of all-cause death, myocardial infarction, or stroke in patients with left main or multivessel CAD. The advantage of CABG over PCI with DES was particularly pronounced in those with multivessel CAD. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights

  18. Randomized Comparison of Ridaforolimus- and Zotarolimus-Eluting Coronary Stents in Patients With Coronary Artery Disease: Primary Results From the BIONICS Trial (BioNIR Ridaforolimus-Eluting Coronary Stent System in Coronary Stenosis).

    Science.gov (United States)

    Kandzari, David E; Smits, Pieter C; Love, Michael P; Ben-Yehuda, Ori; Banai, Shmuel; Robinson, Simon D; Jonas, Michael; Kornowski, Ran; Bagur, Rodrigo; Iniguez, Andres; Danenberg, Haim; Feldman, Robert; Jauhar, Rajiv; Chandna, Harish; Parikh, Manish; Perlman, Gidon Y; Balcells, Mercedes; Markham, Peter; Ozan, Melek Ozgu; Genereux, Philippe; Edelman, Elazer R; Leon, Martin B; Stone, Gregg W

    2017-10-03

    The safety and efficacy of a novel cobalt alloy-based coronary stent with a durable elastomeric polymer eluting the antiproliferative agent ridaforolimus for treatment of patients with coronary artery disease is undetermined. A prospective, international 1:1 randomized trial was conducted to evaluate in a noninferiority design the relative safety and efficacy of ridaforolimus-eluting stents (RESs) and slow-release zotarolimus-eluting stents among 1919 patients undergoing percutaneous coronary intervention at 76 centers. Inclusion criteria allowed enrollment of patients with recent myocardial infarction, total occlusions, bifurcations lesions, and other complex conditions. Baseline clinical and angiographic characteristics were similar between the groups. Overall, mean age was 63.4 years, 32.5% had diabetes mellitus, and 39.7% presented with acute coronary syndromes. At 12 months, the primary end point of target lesion failure (composite of cardiac death, target vessel-related myocardial infarction, and target lesion revascularization) was 5.4% for both devices (upper bound of 1-sided 95% confidence interval 1.8%, P noninferiority =0.001). Definite/probable stent thrombosis rates were low in both groups (0.4% RES versus 0.6% zotarolimus-eluting stent, P =0.75); 13-month angiographic in-stent late lumen loss was 0.22±0.41 mm and 0.23±0.39 mm ( P noninferiority =0.004) for the RES and zotarolimus-eluting stent groups, respectively, and intravascular ultrasound percent neointimal hyperplasia was 8.10±5.81 and 8.85±7.77, respectively ( P noninferiority =0.01). In the present trial, which allowed broad inclusion criteria, the novel RESs met the prespecified criteria for noninferiority compared with zotarolimus-eluting stents for the primary end point of target lesion failure at 12 months and had similar measures of late lumen loss. These findings support the safety and efficacy of RESs in patients who are representative of clinical practice. URL: http

  19. Drug-eluting stents vs. coronary artery bypass-grafting in coronary heart disease

    Directory of Open Access Journals (Sweden)

    Hagen, Anja

    2008-12-01

    Full Text Available Background: Coronary artery bypass graft (CABG and percutaneous revascularisations with implantation of drug-eluting stents (DES are important treatment methods in coronary heart disease (CHD. Research questions: The evaluation addresses questions on medical efficacy, health economic parameters as well as ethic, social and legal implications in the use of DES vs. CABG in CHD patients. Methods: A systematic literature search was conducted in December 2006 in the most important electronic databases beginning from 2004. Register data and controlled clinical studies were included in the evaluation. Additionally, a health economic modelling was conducted. Results: Medical evaluation: The literature search yielded 2,312 hits. 14 publications about six controlled clinical studies and five publications about two registers were included into the evaluation. Register data showed low mortality (0.2% to 0.7% and low rates of myocardial infarction (0.5% to 1.4% during hospital stay. In patients with stenosis of the left anterior descending coronary artery one study showed in several analyses a significantly higher rate of reinterventions and a significantly higher rate of repeated angina pectoris for DES up to two years after the implantation (16.8% vs. 3.6% and 35% vs. 8%. In patients with left main coronary artery stenosis two studies revealed a significantly higher survival without myocardial infarction and stroke for DES up to one year (96% vs. 79% and 95% vs. 91% and two studies a significantly higher rate of revascularisations up to two years (20% vs. 4% and 25% vs. 5% after the primary intervention. In patients with multivessel disease, one study found a significantly higher mortality and myocardial infarction rate for CABG at one year (2.7% vs. 1.0% and 4.2% vs. 1.3%. The rate of revascularisations was significantly higher in two studies up to two years after DES implantation (8.5% vs. 4.2% and 14.2% vs. 5.3%. The rate at repeated angina pectoris was

  20. Advantages of novel BioMimeTM Sirolimus Eluting Coronary Stent system. Moving towards biomimicry.

    Science.gov (United States)

    Upendra, K; Sanjeev, B

    2012-02-01

    Since the first reported use of percutaneous transluminal coronary angioplasty (PTCA), advancements in interventional cardiology arena have been fast paced. Within the last ten years, these developments have been exponential. Developers & clinicians are fast adapting from the learning curve awarded by the time course of DES evolution. In that light BioMimeTM Sirolimus Eluting Coronary Stent comes as a fresh thought in taking stents towards a biomimicry concept. The stent is built on an ultra-low strut thickness (65 µm) cobalt chromium stent platform, using an intelligent hybrid of close and open cells allowing for morphology mediated expansion, employs a well known anti-proliferative - Sirolimus that elutes from a biodegradable co-polymer formulation in 30 days and ensures high coating integrity and low coating thickness of 2 µm. The resultant stent demonstrates almost 100% endothelialization at 30 days in preclinical model and zero percent MACE >18 months in the primary efficacy and safety clinical study.

  1. Clopidogrel discontinuation within the first year after coronary drug-eluting stent implantation

    DEFF Research Database (Denmark)

    Thim, Troels; Johansen, Martin Berg; Chisholm, Gro Egholm

    2014-01-01

    BACKGROUND: The impact of adherence to the recommended duration of dual antiplatelet therapy after first generation drug-eluting stent implantation is difficult to assess in real-world settings and limited data are available. METHODS: We followed 4,154 patients treated with coronary drug-eluting ......BACKGROUND: The impact of adherence to the recommended duration of dual antiplatelet therapy after first generation drug-eluting stent implantation is difficult to assess in real-world settings and limited data are available. METHODS: We followed 4,154 patients treated with coronary drug......-eluting stents in Western Denmark for 1 year and obtained data on redeemed clopidogrel prescriptions and major adverse cardiovascular events (MACE, i.e., cardiac death, myocardial infarction, or stent thrombosis) from medical databases. RESULTS: Discontinuation of clopidogrel within the first 3 months after...... stent implantation was associated with a significantly increased rate of MACE at 1-year follow-up (hazard ratio (HR) 2.06; 95% confidence interval (CI): 1.08-3.93). Discontinuation 3-6 months (HR 1.29; 95% CI: 0.70-2.41) and 6-12 months (HR 1.29; 95% CI: 0.54-3.07) after stent implantation were...

  2. A multicenter post-marketing evaluation of the Elixir DESolve® Novolimus-eluting bioresorbable coronary scaffold system: First results from the DESolve PMCF study.

    Science.gov (United States)

    Nef, Holger; Wiebe, Jens; Boeder, Niklas; Dörr, Oliver; Bauer, Timm; Hauptmann, Karl-Eugen; Latib, Azeem; Colombo, Antonio; Fischer, Dieter; Rudolph, Tanja; Foin, Nicolas; Richardt, Gert; Hamm, Christian

    2018-03-06

    To date, experience with bioresorbable scaffolds (BRS) that elute agents other than everolimus is limited. Thus, a post-marketing clinical follow-up study was conducted to evaluate the continued safety and effectiveness of the DESolve® NOVOLIMUS™ Eluting BRS as treatment for patients with stable coronary artery disease. The DESolve BRS combines a poly-l-lactide-based backbone with a biodegradable polylactide-based polymer and Novolimus, a macrocyclic lactone mTOR inhibitor. One hundred and two patients (mean age 62 years, 77.5% male) were enrolled at 10 European sites. Comparison of baseline and post-procedural angiographic assessment was performed, and a device-oriented composite endpoint (comprising cardiac death, target vessel myocardial infarction, and clinically driven target lesion revascularization) and rate of scaffold thrombosis at 12 months were examined. The device was successfully delivered and deployed in 98.2% (107/109) of the lesions, with two failures to cross the lesion. A total of 100 patients (109 lesions) were treated with a DESolve BRS. Post-procedural angiographic assessment indicated an in-scaffold acute gain of 1.54 ± 0.44 mm, with a reduction in % diameter stenosis from 61.00 ± 11.29 to 12.69 ± 0.44. At 12 months, the device-oriented composite endpoint had occurred in 3.0% (3/100) of patients, with 1.0% (1/100) experiencing scaffold thrombosis and myocardial infarction and 3.0% (3/100) undergoing target lesion revascularization. There were no cardiac deaths. Results through 12 months indicate that the DESolve BRS is a safe and effective treatment for coronary lesions, though larger, long-term prospective studies are needed. © 2018 Wiley Periodicals, Inc.

  3. Clinical benefits of drug-eluting stent implantation in septuagenarians with coronary artery disease

    International Nuclear Information System (INIS)

    Fang Yuehua; Shen Weifeng; Zhang Ruiyan; Zhang Jiansheng; Hu Jian; Zhang Xian; Zheng Aifang

    2005-01-01

    Objective: This study evaluated the safety and long-term outcomes of drug-eluting stents in septuagenarians with coronary artery disease. Methods: Two hundred and thirty-nine consecutive patients with coronary artery disease underwent drug-eluting stenting, including 88 patients aged ≥70 years (group A) and 151 aged <70 years (group B). Baseline clinical characteristics, procedural success rate, occurrence of cardiac events during follow-up were recorded and compared between the two groups. Results: Procedural success rate and complications were similar for the two groups. During follow-up, group A had higher recurrence rate of chest pain than group B (23.9% vs. 7.3%, P<0.001), and occurrence of cardiac events was higher in group A than in group B (5.7% vs. 2.7%, P<0.296). There was no significant difference in the frequency of restenosis between the two groups. Conclusions: Drug-eluting stent implantation for septuagenarians with coronary artery disease is safe but may have more recurrence of angina than younger ones during long-term follow-up. (authors)

  4. Clinical outcomes in low risk coronary artery disease patients treated with different limus-based drug-eluting stents--a nationwide retrospective cohort study using insurance claims database.

    Directory of Open Access Journals (Sweden)

    Chao-Lun Lai

    Full Text Available The clinical outcomes of different limus-based drug-eluting stents (DES in a real-world setting have not been well defined. The aim of this study was to investigate the clinical outcomes of three different limus-based DES, namely sirolimus-eluting stent (SES, Endeavor zotarolimus-eluting stent (E-ZES and everolimus-eluting stent (EES, using a national insurance claims database. We identified all patients who received implantation of single SES, E-ZES or EES between January 1, 2007 and December 31, 2009 from the National Health Insurance claims database, Taiwan. Follow-up was through December 31, 2011 for all selected clinical outcomes. The primary end-point was all-cause mortality. Secondary end-points included acute coronary events, heart failure needing hospitalization, and cerebrovascular disease. Cox regression model adjusting for baseline characteristics was used to compare the relative risks of different outcomes among the three different limus-based DES. Totally, 6584 patients were evaluated (n=2142 for SES, n=3445 for E-ZES, and n=997 for EES. After adjusting for baseline characteristics, we found no statistically significant difference in the risk of all-cause mortality in three DES groups (adjusted hazard ratio [HR]: 1.14, 95% confidence interval [CI]: 0.94-1.38, p=0.20 in E-ZES group compared with SES group; adjusted HR: 0.77, 95% CI: 0.54-1.10, p=0.15 in EES group compared with SES group. Similarly, we found no difference in the three stent groups in risks of acute coronary events, heart failure needing hospitalization, and cerebrovascular disease. In conclusion, we observed no difference in all-cause mortality, acute coronary events, heart failure needing hospitalization, and cerebrovascular disease in patients treated with SES, E-ZES, and EES in a real-world population-based setting in Taiwan.

  5. A randomized, controlled, multicenter trial to evaluate the safety and efficacy of Zotarolimus- vs. Paclitaxel-eluting stents in de novo occlusive lesions in coronary arteries

    DEFF Research Database (Denmark)

    Chevalier, Bernard; Dimario, Carlo; Neumann, Franz-Josef

    2013-01-01

    The ZOMAXX I trial tested the noninferiority of a zotarolimus-eluting coronary stent (ZoMaxx(™) ) when compared with a paclitaxel-eluting coronary stent (Taxus(™) Express(2™) ) in a randomized trial of percutaneous intervention for de novo coronary artery stenosis. Angiographic analysis at the pr...

  6. Clinical evaluation of domestic biodegradable drug-eluting stents in the treatment of coronary heart disease

    International Nuclear Information System (INIS)

    Yu Hongying; Suo Chuantao; Shang Ruiping

    2009-01-01

    Objective: To evaluate the safety and efficacy of domestic biodegradable drug-eluting stent, EXCEL, in clinical treatment of coronary heart disease. Methods: During the period of Jan. 2008-Oct. 2008, 100 patients with coronary heart disease who consented to PCI and postoperative coronary angiography were selected and enrolled in the study. The patients were divided into EXCEL group (n = 58) and Cypher group (n = 42). The immediate successful rate of interventional therapy and the complications occurred during hospitalization were observed. Postoperative follow-up and checkup coronary angiography were conducted. Results: No significant difference in the relevant clinical data, in the number and type of diseased coronary branch and in the mean length of implanted stents existed between two groups. Also, no statistically significant difference in the occurrence of major adverse cardiac event (MACE), in-stent restenosis and thrombosis was present between two groups. Conclusion: Compared with Cypher stenting, EXCEL stenting carries similar, i.e. rather low, occurrence of MACE and in-stent restenosis. (authors)

  7. Drug-eluting stents versus bare-metal stents for acute coronary syndrome

    DEFF Research Database (Denmark)

    Feinberg, Joshua; Nielsen, Emil Eik; Greenhalgh, Janette

    2017-01-01

    -EXPANDED, and BIOSIS from their inception to January 2017. We also searched two clinical trials registers, the European Medicines Agency and the US Food and Drug Administration databases, and pharmaceutical company websites. In addition, we searched the reference lists of review articles and relevant trials. SELECTION...... CRITERIA: Randomised clinical trials assessing the effects of drug-eluting stents versus bare-metal stents for acute coronary syndrome. We included trials irrespective of publication type, status, date, or language. DATA COLLECTION AND ANALYSIS: We followed our published protocol and the methodological...

  8. Anti-Inflammatory Effect of Gallic Acid-Eluting Stent in a Porcine Coronary Restenosis Model

    Science.gov (United States)

    Seob Lim, Kyung; Park, Jun-Kyu; Ho Jeong, Myung; Ho Bae, In; Sung Park, Dae; Won Shim, Jae; Ha Kim, Jung; Kuk Kim, Hyun; Soo Kim, Sung; Sun Sim, Doo; Joon Hong, Young; Han Kim, Ju; Ahn, Youngkeun

    2018-01-01

    Background Gallic acid (3,4,5-trihydroxybenzoic acid) is a natural polyphenol and strong natural antioxidant found abundantly in red wine and green tea. The aim of this study was to examine the anti-inflammatory effect of a novel gallic acid-eluting stent in a porcine coronary restenosis model. Methods Fifteen pigs were randomized into three groups; in which a total of 30 coronary arteries (10 in each group) were implanted with gallic acid-eluting stents (GESs, n = 10), gallic acid and sirolimus-eluting stents (GSESs, n = 10), or sirolimus-eluting stents (SESs, n = 10). Histopathologic analysis was performed 28 days after stenting. Results There were no significant differences in injury score and fibrin score among the groups, however there were significant differences in the internal elastic lamina (4.0 ± 0.83 mm2 in GES vs. 3.0 ± 0.53 mm2 in GSES vs. 4.6 ± 1.43 mm2 in SES, p < 0.0001), lumen area (2.3 ± 0.49 mm2 in GES vs. 1.9 ± 0.67 mm2 in GSES vs. 2.9 ± 0.56 mm2 in SES, p < 0.0001), neointimal area (1.7 ± 0.63 mm2 in GES vs. 1.1 ± 0.28 mm2 in GSES vs. 1.7 ± 1.17 mm2 in SES, p < 0.05), and percent area of stenosis (42.4% ± 9.22% in GES vs. 38.2% ± 12.77% in GSES vs. 33.9% ± 15.64% in SES, p < 0.05). The inflammation score was significantly lower in the GES and GSES groups compared to that in the SES group [1.0 (range: 1.0 to 2.0) in GES vs. 1.0 (range: 1.0 to 1.0) in GSES vs. 1.5 (range: 1.0 to 3.0) in SES, p < 0.05]. Conclusions The GES group had a greater percent area of stenosis than the SES group. Although gallic acid in the GES and GSES groups did not show a synergistic effect in suppressing neointimal hyperplasia, it resulted in greater inhibition of the inflammatory reaction in the porcine coronary restenosis model than in the SES group. PMID:29844643

  9. Association of Adventitial Vasa Vasorum and Inflammation With Coronary Hyperconstriction After Drug-Eluting Stent Implantation in Pigs In Vivo.

    Science.gov (United States)

    Nishimiya, Kensuke; Matsumoto, Yasuharu; Shindo, Tomohiko; Hanawa, Kenichiro; Hasebe, Yuhi; Tsuburaya, Ryuji; Shiroto, Takashi; Takahashi, Jun; Ito, Kenta; Ishibashi-Ueda, Hatsue; Yasuda, Satoshi; Shimokawa, Hiroaki

    2015-01-01

    The importance of adventitial inflammation has been implicated for the pathogenesis of coronary artery disease. However, the roles of adventitial changes in drug-eluting stent (DES)-induced coronary hyperconstriction remain largely unknown. In the present study, this issue in pigs in vivo with a special reference to adventitial vasa vasorum (VV) formation and Rho-kinase activation, a central mechanism of coronary vasospasm, was examined. Each animal received a sirolimus-eluting stent (SES) and a biolimus A9-eluting stent (BES), one in the left anterior descending and another in the left circumflex coronary arteries in a randomized manner (n=18). After 1, 3 and 6 months, coronary vasomotion was examined. At 1 month, coronary vasoconstriction to serotonin was significantly enhanced at the SES edges as compared with the BES edges (SES, 52±7% vs. BES, 22±3%, Pmicro-CT showed VV augmentation at the SES site, extending to the proximal and distal edges. Immunostainings demonstrated that VV formation, macrophage infiltration in the adventitia and Rho-kinase expressions/activation were significantly enhanced at the SES edges as compared with the BES edges. The DES with durable polymers enhances VV formation and inflammation in the adventitia, associating with the pathogenesis of DES-induced coronary hyperconstriction through Rho-kinase activation in pigs in vivo.

  10. Bioabsorbable polymer-coated sirolimus-eluting stent implantation preserves coronary vasomotion: A DESSOLVE II trial sub-study.

    Science.gov (United States)

    Rusinaru, Dan; Vrolix, Mathias; Verheye, Stefan; Chowdhary, Saqib; Schoors, Danny; Di Mario, Carlo; Desmet, Walter; Donohoe, Dennis J; Ormiston, John A; Knape, Charlene; Bezerra, Hiram; Lansky, Alexandra; Wijns, William

    2015-12-01

    We studied coronary vasomotion in patients treated with the Mistent(®) absorbable polymer sirolimus-eluting stent (APSES) and in patients implanted with the Endeavor(®) zotarolimus-eluting stent (ZES). First generation (1st-gen) drug-eluting stents (DES) induce persistent vasomotor dysfunction in the treated coronary artery. It is unknown whether and to what extent the implantation of an absorbable polymer DES impairs coronary vasomotion. This sub-study of the DESSOLVE II trial included 19 APSES Mistent(®) and 10 ZES Endeavor(®) patients. Incremental atrial pacing and quantitative coronary angiography were used to assess vasomotion proximal and distal to the stent and in a reference segment at 9 months after implantation. Percent changes in vessel diameter with pacing versus baseline were calculated and compared. Vasomotor response of the APSES group was also compared with changes observed in a historical group of 17 patients implanted with a 1st-gen sirolimus-eluting stent (SES). Normal vasomotion (vasodilatation) was preserved and of comparable magnitude in the APSES and in the ZES group both proximally (P = 0.34) and distally (P = 0.38) to the stent. This finding was not observed in the 1st-gen SES group showing marked pacing-induced vasoconstriction at both stent edges (P absorbable polymer sirolimus-eluting stent is associated with preserved coronary vasomotion, comparable to that observed after implantation of the Endeavor(®) ZES, and distinct from 1st-gen SES which induce coronary vasomotor dysfunction. © 2015 Wiley Periodicals, Inc.

  11. Type D personality predicts chronic anxiety following percutaneous coronary intervention in the drug-eluting stent era

    DEFF Research Database (Denmark)

    Spindler, Helle; Pedersen, Susanne S.; Serruys, Patrick W.

    2007-01-01

      Background: Anxiety is an often overlooked risk factor in coronary artery disease (CAD). Hence, little is known about predictors of unremitting chronic anxiety in CAD patients. This study examined whether the distressed personality (Type D) predicts chronic anxiety post percutaneous coronary...... months post-PCI. Results: Of 167 patients anxious at 6 months, 108 (65%) were still anxious 12 months post-PCI. Significant univariable predictors of chronic anxiety were Type D personality (OR:3.17: 95% CI:1.64-6.14) and sirolimus-eluting stents (OR:0.51; 95% CI:0.27-0.98), with sirolimus-eluting stents...... showing a protective effect. In multivariable analyses, Type D personality (OR:3.31; 95% CI:1.59-6.87) and sirolimus-eluting stents (OR:0.44; 95% CI:0.21-0.92) remained significant independent predictors of chronic anxiety adjusting for depressive symptoms at 6 months, and demographic and clinical risk...

  12. Spectral Analysis Related to Bare-Metal and Drug-Eluting Coronary Stent Implantation

    Energy Technology Data Exchange (ETDEWEB)

    Silva, Rose Mary Ferreira Lisboa da, E-mail: roselisboa@cardiol.br [Faculdade de Medicina da UFMG, Divinópolis, MG (Brazil); Silva, Carlos Augusto Bueno [Faculdade de Medicina da UFMG, Divinópolis, MG (Brazil); Belo Horizonte, Hospital São João de Deus, Divinópolis, MG (Brazil); Greco, Otaviano José [Belo Horizonte, Hospital São João de Deus, Divinópolis, MG (Brazil); Moreira, Maria da Consolação Vieira [Faculdade de Medicina da UFMG, Divinópolis, MG (Brazil)

    2014-08-15

    The autonomic nervous system plays a central role in cardiovascular regulation; sympathetic activation occurs during myocardial ischemia. To assess the spectral analysis of heart rate variability during stent implantation, comparing the types of stent. This study assessed 61 patients (mean age, 64.0 years; 35 men) with ischemic heart disease and indication for stenting. Stent implantation was performed under Holter monitoring to record the spectral analysis of heart rate variability (Fourier transform), measuring the low-frequency (LF) and high-frequency (HF) components, and the LF/HF ratio before and during the procedure. Bare-metal stent was implanted in 34 patients, while the others received drug-eluting stents. The right coronary artery was approached in 21 patients, the left anterior descending, in 28, and the circumflex, in 9. As compared with the pre-stenting period, all patients showed an increase in LF and HF during stent implantation (658 versus 185 ms2, p = 0.00; 322 versus 121, p = 0.00, respectively), with no change in LF/HF. During stent implantation, LF was 864 ms2 in patients with bare-metal stents, and 398 ms2 in those with drug-eluting stents (p = 0.00). The spectral analysis of heart rate variability showed no association with diabetes mellitus, family history, clinical presentation, beta-blockers, age, and vessel or its segment. Stent implantation resulted in concomitant sympathetic and vagal activations. Diabetes mellitus, use of beta-blockers, and the vessel approached showed no influence on the spectral analysis of heart rate variability. Sympathetic activation was lower during the implantation of drug-eluting stents.

  13. Cost effectiveness of drug eluting coronary artery stenting in a UK setting: cost-utility study.

    Science.gov (United States)

    Bagust, A; Grayson, A D; Palmer, N D; Perry, R A; Walley, T

    2006-01-01

    To assess the cost effectiveness of drug eluting stents (DES) compared with conventional stents for treatment of symptomatic coronary artery disease in the UK. Cost-utility analysis of audit based patient subgroups by means of a simple economic model. Tertiary care. 12 month audit data for 2884 patients receiving percutaneous coronary intervention with stenting at the Cardiothoracic Centre Liverpool between January 2000 and December 2002. Risk of repeat revascularisation within 12 months of index procedure and reduction in risk from use of DES. Economic modelling was used to estimate the cost-utility ratio and threshold price premium. Four factors were identified for patients undergoing elective surgery (n = 1951) and two for non-elective surgery (n = 933) to predict risk of repeat revascularisation within 12 months. Most patients fell within the subgroup with lowest risk (57% of the elective surgery group with 5.6% risk and 91% of the non-elective surgery group with 9.9% risk). Modelled cost-utility ratios were acceptable for only one group of high risk patients undergoing non-elective surgery (only one patient in audit data). Restricting the number of DES for each patient improved results marginally: 4% of stents could then be drug eluting on economic grounds. The threshold price premium justifying 90% substitution of conventional stents was estimated to be 112 pound sterling (212 USD, 162 pound sterling) (sirolimus stents) or 89 pound sterling (167 USD, 130 pound sterling) (paclitaxel stents). At current UK prices, DES are not cost effective compared with conventional stents except for a small minority of patients. Although the technology is clearly effective, general substitution is not justified unless the price premium falls substantially.

  14. Randomized comparison of a sirolimus-eluting Orsiro stent with a biolimus-eluting Nobori stent in patients treated with percutaneous coronary intervention

    DEFF Research Database (Denmark)

    Jensen, Lisette Okkels; Thayssen, Per; Maeng, Michael

    2015-01-01

    BACKGROUND: Third-generation coronary drug-eluting stents (DES) with biodegradable polymers have been designed to improve safety and efficacy. We designed a large scale registry-based randomized clinical trial to compare 2 third-generation DES: a thin strut, cobalt-chromium DES with silicon carbide......-coating releasing sirolimus from a biodegradable polymer (O-SES, Orsiro; Biotronik, Bülach, Switzerland) with the stainless steel biodegradable polymer biolimus-eluting Nobori stents (N-BES, Nobori; Terumo, Tokyo, Japan) in an all-comer patient population. DESIGN: The multicenter SORT OUT VII trial (NCT01879358...... will be used. An event rate of 6.5% is assumed in each stent group. With a sample size of 1,157 patients in each treatment arm, a 2-group large-sample normal approximation test of proportions with a 1-sided 5% significance level will have 90% power to detect noninferiority of the O-SES compared with the N...

  15. Outcomes of coronary artery bypass grafting versus percutaneous coronary intervention with drug-eluting stents for patients with multivessel coronary artery disease.

    Science.gov (United States)

    Javaid, Aamir; Steinberg, Daniel H; Buch, Ashesh N; Corso, Paul J; Boyce, Steven W; Pinto Slottow, Tina L; Roy, Probal K; Hill, Peter; Okabe, Teruo; Torguson, Rebecca; Smith, Kimberly A; Xue, Zhenyi; Gevorkian, Natalie; Suddath, William O; Kent, Kenneth M; Satler, Lowell F; Pichard, Augusto D; Waksman, Ron

    2007-09-11

    Advances in coronary artery bypass grafting (CABG) surgery and percutaneous coronary intervention (PCI) with drug-eluting stents have dramatically improved results of these procedures. The optimal treatment for patients with multivessel coronary artery disease is uncertain given the lack of prospective, randomized data reflecting current practice. This study represents a "real-world" evaluation of current technology in the treatment of multivessel coronary artery disease. A total of 1680 patients undergoing revascularization for multivessel coronary artery disease were identified. Of these, 1080 patients were treated for 2-vessel disease (196 CABG and 884 PCI) and 600 for 3-vessel disease (505 CABG and 95 PCI). One-year mortality, cerebrovascular events, Q-wave myocardial infarction, target vessel failure, and composite major adverse cardiovascular and cerebrovascular events were compared between the CABG and PCI cohorts. Outcomes were adjusted for baseline covariates and reported as hazard ratios. The unadjusted major adverse cardiovascular and cerebrovascular event rate was reduced with CABG for patients with 2-vessel disease (9.7% CABG versus 21.2% PCI; P<0.001) and 3-vessel disease (10.8% CABG versus 28.4% PCI; P<0.001). Adjusted outcomes showed increased major adverse cardiovascular and cerebrovascular event with PCI for patients with 2-vessel (hazard ratio 2.29; 95% CI 1.39 to 3.76; P=0.01) and 3-vessel disease (hazard ratio 2.90; 95% CI 1.76 to 4.78; P<0.001). Adjusted outcomes for the nondiabetic subpopulation demonstrated equivalent major adverse cardiovascular and cerebrovascular event with PCI for 2-vessel (hazard ratio 1.77; 95% CI 0.96 to 3.25; P=0.07) and 3-vessel disease (hazard ratio 1.70; 95% CI 0.77 to 3.61; P=0.19). Compared with PCI with drug-eluting stents, CABG resulted in improved major adverse cardiovascular and cerebrovascular event in patients with 2- and 3-vessel coronary artery disease, primarily in those with underlying diabetes

  16. Toxic vessel reaction to an absorbable polymer-based paclitaxel-eluting stent in pig coronary arteries.

    Science.gov (United States)

    Jabara, Refat; Chronos, Nicolas; Tondato, Fernando; Conway, Damian; Molema, Warner; Park, Kenneth; Mabin, Tom; King, Spencer; Robinson, Keith

    2006-08-01

    The goal of this study was to evaluate a new drug-eluting stent (DES) comprising a bioabsorbable polymer eluting a moderate dose of paclitaxel in a clinically relevant animal model. Although DES limit restenosis, adverse vascular pathologies and toxicities continue to be of major concern. Optimization of DES components, especially completely absorbable polymers, may reduce these toxicities. Bare-metal (BM), absorbable polymer coating only (POLY), and polymer-based paclitaxel-eluting (PACL) stents were implanted in porcine coronary arteries using intravascular ultrasound (IVUS) to optimize stent apposition. The dose density of paclitaxel was 0.30-0.35 mcg/mm2, with in vitro elution studies demonstrating a gradual elution over 6-8 weeks. The animals were terminated at 1 week, 1 month and 3 months. Histopathologic and histomorphometric analyses were perform. The arteries with PACL showed extensive smooth muscle cell necrosis at 1 week and poor apposition of stent struts at 1 month (malapposition measured as gap width between strut and internal elastic lamina), with greater gap width compared to the BM and POLY groups (0.22 mm +/- 0.02 vs. 0.03 mm +/- 0.02 and 0.02 mm +/- 0.01, respectively; p stent malapposition and late neointimal thickening. Since the therapeutic window for paclitaxel may be narrower than currently inferred, thorough preclinical testing coupled with the polymer development process for stents eluting paclitaxel is needed.

  17. Outcomes after revascularisation with everolimus- and sirolimus-eluting stents in patients with acute coronary syndromes and stable angina pectoris

    DEFF Research Database (Denmark)

    Antonsen, Lisbeth; Thayssen, Per; Hansen, Henrik S

    2014-01-01

    ): cardiac death, myocardial infarction (MI), stent thrombosis, or target vessel revascularisation within 18 months. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated for the endpoints. At 18-month follow-up, patients with ACS had higher rates of MACE compared to patients with SAP (8...

  18. Cost-effectiveness of drug-eluting stents versus bare-metal stents in patients undergoing percutaneous coronary intervention

    OpenAIRE

    Baschet, Louise; Bourguignon, Sandrine; Marque, S?bastien; Durand-Zaleski, Isabelle; Teiger, Emmanuel; Wilquin, Fanny; Levesque, Karine

    2016-01-01

    Objective To determine the cost-effectiveness of drug-eluting stents (DES) compared with bare-metal stents (BMS) in patients requiring a percutaneous coronary intervention in France, using a recent meta-analysis including second-generation DES. Methods A cost-effectiveness analysis was performed in the French National Health Insurance setting. Effectiveness settings were taken from a meta-analysis of 117?762 patient-years with 76 randomised trials. The main effectiveness criterion was major c...

  19. Improved two-year outcomes after drug-eluting versus bare-metal stent implantation in women and men with large coronary arteries

    DEFF Research Database (Denmark)

    Hansen, K W; Kaiser, C; Hvelplund, A

    2013-01-01

    To investigate the importance of vessel size on outcome differences by comparing the effects of drug-eluting stents (DES) versus bare-metal stents (BMS) in women and men with large coronary vessels.......To investigate the importance of vessel size on outcome differences by comparing the effects of drug-eluting stents (DES) versus bare-metal stents (BMS) in women and men with large coronary vessels....

  20. Randomized clinical comparison of the dual-therapy CD34 antibody-covered sirolimus-eluting Combo stent with the sirolimus-eluting Orsiro stent in patients treated with percutaneous coronary intervention

    DEFF Research Database (Denmark)

    Jakobsen, Lars; Christiansen, Evald H; Maeng, Michael

    2018-01-01

    Background: The Combo stent (OrbusNeich, Hoevelaken, the Netherlands) combining an abluminal, bioabsorbable polymer eluting sirolimus with a luminal CD34+ antibody to capture endothelial progenitor cells has been developed to further improve safety and efficacy of coronary interventions. We have...... designed a large-scale registry-based randomized clinical trial to compare the Combo stent to the Orsiro stent (Biotronik, Bülach, Switzerland) in patients undergoing percutaneous coronary intervention. Methods: The SORT OUT X study will randomly assign 3,140 patients to treatment with Combo or Orsiro...... stents at 3 sites in Western Denmark. Patients are eligible if they are ≥18 years old, have chronic stable coronary artery disease or acute coronary syndromes, and have ≥1 coronary lesion with >50% diameter stenosis requiring treatment with a drug-eluting stent. The primary end point target lesion...

  1. Outcome of Sirolimus-Eluting Versus Zotarolimus-Eluting Coronary Stent Implantation in Patients With and Without Diabetes Mellitus (a SORT OUT III Substudy)

    DEFF Research Database (Denmark)

    Maeng, Michael; Jensen, Lisette O; Tilsted, Hans-Henrik

    2011-01-01

    Diabetes is associated with an increased risk of major adverse cardiac events after percutaneous coronary intervention. We compared clinical outcomes in patients with and without diabetes mellitus treated with the second-generation Endeavor zotarolimus-eluting stent (ZES) or the first...... cardiac events defined as a composite of cardiac death, myocardial infarction, or target vessel revascularization. Secondary end points included these individual end points plus all-cause mortality and target lesion revascularization. In diabetic patients, use of ZES compared to SES was associated.......90 to 13.1), and target lesion revascularization (12.4% vs 1.2%, hazard ratio 11.0, 95% confidence interval 2.59 to 47.1). In patients without diabetes differences in absolute risk decrease were smaller but similarly favored SES. In conclusion, implantation of ZESs compared to SESs is associated...

  2. Biolimus-eluting biodegradable polymer-coated stent versus durable polymer-coated sirolimus-eluting stent in unselected patients receiving percutaneous coronary intervention (SORT OUT V)

    DEFF Research Database (Denmark)

    Christiansen, Evald Høj; Jensen, Lisette Okkels; Thayssen, Per

    2013-01-01

    Third-generation biodegradable polymer drug-eluting stents might reduce the risk of stent thrombosis compared with first-generation permanent polymer drug-eluting stents. We aimed to further investigate the effects of a biodegradable polymer biolimus-eluting stent compared with a durable polymer......-coated sirolimus-eluting stent in a population-based setting....

  3. Percutaneous coronary intervention with second-generation drug-eluting stent versus bare-metal stent: Systematic review and cost-benefit analysis.

    Science.gov (United States)

    Poder, Thomas G; Erraji, Jihane; Coulibaly, Lucien P; Koffi, Kouamé

    2017-01-01

    Drug-eluting stents (DESs) were considered as ground-breaking technology promising to eradicate restenosis and the necessity to perform multiple revascularization procedures subsequent to percutaneous coronary intervention. Soon after DESs were released on the market, however, there were reports of a potential increase in mortality and of early or late thrombosis. In addition, DESs are far more expensive than bare-metal stents (BMSs), which has led to their limited use in many countries. The technology has improved over the last few years with the second generation of DESs (DES-2). Moreover, costs have come down and an improved safety profile with decreased thrombosis has been reported. Perform a cost-benefit analysis of DES-2s versus BMSs in the context of a publicly funded university hospital in Quebec, Canada. A systematic review of meta-analyses was conducted between 2012 and 2016 to extract data on clinical effectiveness. The clinical outcome of interest for the cost-benefit analysis was target-vessel revascularization (TVR). Cost units are those used in the Quebec health-care system. The cost-benefit analysis was based on a 2-year perspective. Deterministic and stochastic models (discrete-event simulation) were used, and various risk factors of reintervention were considered. DES-2s are much more effective than BMSs with respect to TVR rate ratio (i.e., 0.29 to 0.62 in more recent meta-analyses). DES-2s seem to cause fewer deaths and in-stent thrombosis than BMSs, but results are rarely significant, with the exception of the cobalt-chromium everolimus DES. The rate ratio of myocardial infraction is systematically in favor of DES-2s and very often significant. Despite the higher cost of DES-2s, fewer reinterventions can lead to huge savings (i.e., -$479 to -$769 per patient). Moreover, the higher a patient's risk of reintervention, the higher the savings associated with the use of DES-2s. Despite the higher purchase cost of DES-2s compared to BMSs

  4. The role of drug-eluting balloons alone or in combination with drug-eluting stents in the treatment of de novo diffuse coronary disease.

    Science.gov (United States)

    Costopoulos, Charis; Latib, Azeem; Naganuma, Toru; Sticchi, Alessandro; Figini, Filippo; Basavarajaiah, Sandeep; Carlino, Mauro; Chieffo, Alaide; Montorfano, Matteo; Naim, Charbel; Kawaguchi, Masanori; Giannini, Francesco; Colombo, Antonio

    2013-11-01

    This study sought to investigate the role of drug-eluting balloons (DEB) alone or in combination with drug-eluting stents (DES) in the treatment of diffuse de novo coronary artery disease (CAD) (>25 mm). The use of DEB in diffuse CAD, either alone or in combination with DES, offers an alternative to stenting alone. Data regarding DEB in this context are limited. We retrospectively evaluated all patients treated with DEB for diffuse CAD between June 2009 and October 2012. Endpoints analyzed were major adverse cardiac events, defined as all-cause death, myocardial infarction, and target vessel revascularization (TVR), as well as TVR and target lesion revascularization separately. Results were compared with those obtained from a cohort of patients with similar characteristics treated with DES alone. A total of 69 patients (93 lesions) were treated with DEB ± DES, and 93 patients with DES alone (93 lesions). A high proportion of patients were diabetic (46.4% vs. 44.1%, p = 0.77). Of the DEB-treated lesions, 56.0% were treated with DEB alone, 7.4% with DEB and DES as bail out, and 36.6% with DES and DEB as part of a hybrid approach for very long disease. Outcome rates with DEB ± DES were comparable to those with DES alone at 2-year follow-up (major adverse cardiac events = 20.8% vs. 22.7%, p = 0.74; TVR = 14.8% vs. 11.5%, p = 0.44; target lesion revascularization = 9.6% vs. 9.3%, p = 0.84). DEB may have a role in the treatment of diffuse de novo CAD, either alone in smaller vessels or in combination with DES in very long disease. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  5. Morphological and functional evaluation of the bioresorption of the bioresorbable everolimus-eluting vascular scaffold using IVUS, echogenicity and vasomotion testing at two year follow-up: a patient level insight into the ABSORB A clinical trial.

    Science.gov (United States)

    Sarno, Giovanna; Bruining, Nico; Onuma, Yoshinobu; Garg, Scot; Brugaletta, Salvatore; De Winter, Sebastiaan; Regar, Evelyn; Thuesen, Leif; Dudek, Dariusz; Veldhof, Susan; Dorange, Cecile; Garcia-Garcia, Hector M; Ormiston, John A; Serruys, Patrick W

    2012-01-01

    The aim of this study was to describe vaso-reactivity (by Acetylcholine and Methergine tests) at 2 year follow-up in parallel with the individual changes in the echogenicity characteristics of the polymer struts of the everolimus eluting bioresorbable vascular scaffold (BVS), from post-treatment to 2 year follow-up, in patients enrolled in the ABSORB Cohort A study. Intravascular ultrasound assessment was performed with a phased array catheter (EagleEye, Volcano Corporation, Cordova, CA, USA) with automated pullback at 0.5 mm per second. The % ratio at 6 months and 2 years [(Scaffold Area post PCI- Lumen Area)/Scaffold Area post PCI] was calculated as a measure of scaffold shrinkage. The % change of hyperechogenicity was defined as: ([post-procedural hyperechogenicity] - [2 year follow up hyperechogenicity])/[post-procedural hyperechogenicity]) × 100. The vasomotion test with intracoronary acetylcholine (10(-6) M) or intravenous methergine (0.4 mg) was performed at 2 years. Overall nine patients received all these analyses and were enrolled in the present analysis. A 50-96% reduction in hyperechogenicity was observed between baseline and 2 years, which corresponded to a change in vasoreactivity between 2 and 22%. A vasoconstriction of the scaffolded segment was observed in the 5 patients, who underwent the methergine test, with a mean decrease in lumen diameter after methergine of 9 ± 7% (P = 0.06), while vasodilatation occurred in the 4 patients who underwent the acetylcholine test with a mean increase in lumen diameter after acetylcholine of 8 ± 5% (P = 0.125). Bioresorption of the BVS is accompanied by re-establishment of both endothelial and non-endothelial dependent vasomotion.

  6. Bioabsorbable drug-eluting vascular scaffold for the treatment of coronary in-stent restenosis: A two center registry

    International Nuclear Information System (INIS)

    Moscarella, Elisabetta; Varricchio, Attilio; Stabile, Eugenio; Franzone, Anna; Granata, Francesco; Rapacciuolo, Antonio; Galasso, Gennaro; Capozzolo, Claudia; Cirillo, Plinio

    2015-01-01

    Background/purpose: Coronary in-stent restenosis (ISR) is a clinical problem for which a satisfactory solution has not been found yet. Bioabsorbable drug eluting vascular scaffolds (BVSs) provide transient vessel scaffolding combined with prolonged drug delivery capability. The aim of this study was to investigate the safety of BVS for the treatment of coronary ISR. Methods/materials: Between January 2013 and June 2013, 27 patients (31 lesions), presenting with either stable or unstable angina due to coronary ISR, were enrolled in a single arm, prospective, open label registry. Primary end point was the occurrence of target vessel revascularization (TVR) at 12 months. Secondary end point was the composite of death, myocardial infarction and TVR at 12 months. Results: A diffuse ISR pattern was present in 70% of the lesions; mean lesion length was 34.6 ± 15. BVS was successfully implanted in all patients with no in hospital MACE. At twelve months of follow up, MACE rate was 18.5%. One patient died for non-cardiac reason, one patient died due to a possible stent thrombosis and TVR was necessary in 3 patients (11.1%). Conclusions: Our data suggest that BVS is safe and technically feasible for treatment of long and diffuse coronary ISR. These data could be considered hypothesis generator for a randomized clinical trial. - Highlights: • A safe therapeutic option for the treatment of diffuse ISR; • Technically feasible; • Associated to a low rate of restenosis recurrence at nine month.

  7. Bioabsorbable drug-eluting vascular scaffold for the treatment of coronary in-stent restenosis: A two center registry

    Energy Technology Data Exchange (ETDEWEB)

    Moscarella, Elisabetta [Division of Cardiology, Seconda Università degli studi di Napoli, AO Dei cColli, PO Monaldi (Italy); Varricchio, Attilio [Division of Cardiology, Department of Advanced Biomedical Sciences, University of Napoli “Federico II”, Napoli (Italy); Stabile, Eugenio, E-mail: geko50@hotmail.com [Laboratory of Invasive Cardiology, Dipartimento di Cardiologia, Presidio Ospedaliero “Monaldi”, Azienda Ospedaliera “Dei Colli”, Napoli (Italy); Franzone, Anna [Laboratory of Invasive Cardiology, Dipartimento di Cardiologia, Presidio Ospedaliero “Monaldi”, Azienda Ospedaliera “Dei Colli”, Napoli (Italy); Granata, Francesco [Division of Cardiology, Seconda Università degli studi di Napoli, AO Dei cColli, PO Monaldi (Italy); Rapacciuolo, Antonio; Galasso, Gennaro [Laboratory of Invasive Cardiology, Dipartimento di Cardiologia, Presidio Ospedaliero “Monaldi”, Azienda Ospedaliera “Dei Colli”, Napoli (Italy); Capozzolo, Claudia [Division of Cardiology, Department of Advanced Biomedical Sciences, University of Napoli “Federico II”, Napoli (Italy); Cirillo, Plinio [Laboratory of Invasive Cardiology, Dipartimento di Cardiologia, Presidio Ospedaliero “Monaldi”, Azienda Ospedaliera “Dei Colli”, Napoli (Italy); and others

    2015-10-15

    Background/purpose: Coronary in-stent restenosis (ISR) is a clinical problem for which a satisfactory solution has not been found yet. Bioabsorbable drug eluting vascular scaffolds (BVSs) provide transient vessel scaffolding combined with prolonged drug delivery capability. The aim of this study was to investigate the safety of BVS for the treatment of coronary ISR. Methods/materials: Between January 2013 and June 2013, 27 patients (31 lesions), presenting with either stable or unstable angina due to coronary ISR, were enrolled in a single arm, prospective, open label registry. Primary end point was the occurrence of target vessel revascularization (TVR) at 12 months. Secondary end point was the composite of death, myocardial infarction and TVR at 12 months. Results: A diffuse ISR pattern was present in 70% of the lesions; mean lesion length was 34.6 ± 15. BVS was successfully implanted in all patients with no in hospital MACE. At twelve months of follow up, MACE rate was 18.5%. One patient died for non-cardiac reason, one patient died due to a possible stent thrombosis and TVR was necessary in 3 patients (11.1%). Conclusions: Our data suggest that BVS is safe and technically feasible for treatment of long and diffuse coronary ISR. These data could be considered hypothesis generator for a randomized clinical trial. - Highlights: • A safe therapeutic option for the treatment of diffuse ISR; • Technically feasible; • Associated to a low rate of restenosis recurrence at nine month.

  8. Stent underexpansion in angiographic guided percutaneous coronary intervention, despite adjunctive balloon post-dilatation, in drug eluting stent era

    Directory of Open Access Journals (Sweden)

    Mehrdad Taherioun

    2014-01-01

    Full Text Available BACKGROUND: Stent underexpansion is the most powerful predictor of long-term stent patency and clinical outcome. The purpose of this study was to evaluate the incidence and predictors of stent underexpansion despite adjunctive post-dilatation with non-compliant balloon. METHODS: After elective coronary stent implantation and adjunctive post-dilatation with non-compliant balloon and optimal angiographic result confirmed by the operator, intravascular ultrasound (IVUS was performed for all the treated lesions. If the treated lesions fulfilled the IVUS criteria, they are considered as the optimal stent group; if not, they are considered as the suboptimal group. RESULTS: From 50 patients enrolled in this study 39 (78% had optimal stent deployment and 11 (22% had suboptimal stent deployment. In the suboptimal group 7 (14% had underexpansion, 2 (4% malposition, and 2 (4% had asymmetry. There were no stent edge dissections detected by IVUS. We did not find any correlation between lesion calcification, ostial lesions, stent length, and stent underexpansion. Stent diameter ≤ 2.75 mm had a strong correlation with stent underexpansion. CONCLUSION: Despite adjunctive post-dilatation with noncompliant balloon, using a relatively small stent diameter was a strong predictor for underexpansion. IVUS guided percutaneous coronary intervention (PCI may be considered for drug eluting stent (DES implantation in relatively small vessels.   Keywords: Stent, Percutaneous Coronary Intervention, Ultrasound, Post-dilatation 

  9. Second generation drug-eluting stents versus bare-metal stents for percutaneous coronary intervention of the proximal left anterior descending artery

    DEFF Research Database (Denmark)

    Mangione, Fernanda Marinho; Biering-Sørensen, Tor; Nochioka, Kotaro

    2017-01-01

    OBJECTIVES: To compare mid-term outcomes between patients undergoing proximal left anterior descending artery (LAD) percutaneous coronary intervention (PCI) with second generation drug-eluting stent (DES) or bare-metal stent (BMS). BACKGROUND: PCI with BMS and first-generation DES have shown to b...

  10. Risk factors for impaired health status differ in women and men treated with percutaneous coronary intervention in the drug-eluting stent era

    DEFF Research Database (Denmark)

    Pedersen, Susanne S.; Ong, Andrew T L; Lemos, Pedro A

    2006-01-01

    In patients treated with percutaneous coronary intervention (PCI) in the drug-eluting stent era, we compared women's and men's health status 6 and 12 months post-PCI and investigated whether predictors of poor health status at 12 months are similar for women and men....

  11. Stent thrombosis, myocardial infarction, and death after drug-eluting and bare-metal stent coronary interventions

    DEFF Research Database (Denmark)

    Jensen, Lisette Okkels; Maeng, Michael; Kaltoft, Anne

    2007-01-01

    OBJECTIVES: The aim of the study was to examine outcomes subsequent to implantation of drug-eluting stents (DES) and bare-metal stents (BMS). BACKGROUND: Use of DES might be associated with increased risk of stent thrombosis (ST), myocardial infarction (MI), and death. METHODS: From January 2002...... through June 2005, data from all percutaneous coronary interventions in western Denmark were prospectively recorded in the Western Denmark Heart Registry; 12,395 consecutive patients (17,152 lesions) treated with stent implantation were followed for 15 months. Data on death and MI were ascertained from...... within 15 months after implantation of DES seems unlikely to outweigh the benefit of these stents. Udgivelsesdato: 2007-Jul-31...

  12. Impact of an endothelial progenitor cell capturing stent on coronary microvascular function: comparison with drug-eluting stents.

    Science.gov (United States)

    Choi, Woong Gil; Kim, Soo Hyun; Yoon, Hyung Seok; Lee, Eun Joo; Kim, Dong Woon

    2015-01-01

    Although drug-eluting stents (DESs) effectively reduce restenosis following percutaneous coronary intervention (PCI), they also delay re-endothelialization and impair microvascular function, resulting in adverse clinical outcomes. Endothelial progenitor cell (EPC) capturing stents, by providing a functional endothelial layer on the stent, have beneficial effects on microvascular function. However, data on coronary microvascular function in patients with EPC stents versus DESs are lacking. Seventy-four patients who previously underwent PCI were enrolled in this study. Microvascular function was evaluated 6 months after PCI based on the index of microvascular resistance (IMR) and the coronary flow reserve (CFR). IMR was calculated as the ratio of the mean distal coronary pressure at maximal hyperemia to the inverse of the hyperemic mean transit time (hTmn). The CFR was calculated by dividing the hTmn by the baseline mean transit time. Twenty-one patients (age, 67.2 ± 9.6 years; male:female, 15:6) with an EPC stent and 53 patients (age, 61.5 ± 14.7 years; male:female, 40:13) with second-generation DESs were included in the study. There were no significant differences in the baseline clinical and angiographic characteristics of the two groups. Angiography performed 6 months postoperatively did not show significant differences in their CFR values. However, patients with the EPC stent had a significantly lower IMR than patients with second-generation DESs (median, 25.5 [interquartile range, 12.85 to 28.18] vs. 29.0 [interquartile range, 15.42 to 39.23]; p = 0.043). Microvascular dysfunction was significantly improved after 6 months in patients with EPC stents compared to those with DESs. The complete re-endothelialization achieved with the EPC stent may provide clinical benefits over DESs, especially in patients with microvascular dysfunction.

  13. Serial Multimodality Imaging and 2-Year Clinical Outcomes of the Novel DESolve Novolimus-Eluting Bioresorbable Coronary Scaffold System for the Treatment of Single De Novo Coronary Lesions.

    Science.gov (United States)

    Abizaid, Alexandre; Costa, Ricardo A; Schofer, Joachim; Ormiston, John; Maeng, Michael; Witzenbichler, Bernhard; Botelho, Roberto V; Costa, J Ribamar; Chamié, Daniel; Abizaid, Andrea S; Castro, Juliana P; Morrison, Lynn; Toyloy, Sara; Bhat, Vinayak; Yan, John; Verheye, Stefan

    2016-03-28

    This study sought to report the late multimodality imaging and clinical outcomes of the novel poly-l-lactic-acid-based DESolve novolimus-eluting bioresorbable coronary scaffold for the treatment of de novo coronary lesions. Bioresorbable scaffolds are an alternative to drug-eluting metallic stents and provide temporary vascular scaffolding, which potentially may allow vessel restoration and reduce the risk of future adverse events. Overall, 126 patients were enrolled at 13 international sites between November 2011 and June 2012. The primary endpoint was in-scaffold late lumen loss at 6 months. Major adverse cardiac events, the main safety endpoint, were defined as the composite of cardiac death, target vessel myocardial infarction, or clinically indicated target lesion revascularization. All patients underwent angiography at 6 months. Serial intravascular ultrasound and optical coherence tomography were performed in a subset of patients. The scaffold device success rate was 97% (n = 122 of 126), and procedural success was 100% (n = 122 of 122). The major adverse cardiac event rate was 3.3% (n = 4 of 122) at 6 months and 7.4% (n = 9 of 122) at 24 months, including 1 probable stent thrombosis within the first month. At 6-month angiographic follow-up, in-scaffold late lumen loss was 0.20 ± 0.32 mm. Paired intravascular ultrasound analysis demonstrated a significant increase in vessel, lumen and scaffold dimensions between post-procedure and 6-month follow-up, and strut-level optical coherence tomography analysis showed full strut coverage in 99 ± 1.7%. Our results showed favorable performance of the DESolve scaffold, effective inhibition of neointimal hyperplasia, and for the first time, early luminal and scaffold growth at 6 months with sustained efficacy and safety through 2 years. (Elixir Medical Clinical Evaluation of the DESolve Novolimus Eluting Bioresorbable Coronary Scaffold System-The DESolve Nx Trial; NCT02086045). Copyright © 2016 American College of

  14. [Fully absorbable drug eluting coronary stent: where do we stand in 2014?].

    Science.gov (United States)

    Kočka, Viktor; Toušek, Petr; Lisa, Libor; Buděšínský, Tomáš

    2014-04-01

    Coronary stent is routinely used in majority percutaneous coronary interventions for a long time. They have an important role, especially, in the first months after intervention. We can consider as a breakthrough point the development of stent which has ability to absorb in intervened artery after a few years. The review presents current techniques of fully absorbable coronary stents and also provides clinical trials and experiences available in 2014. The article continues with discussion between supporters and opponents of this new technique, but definitive conclusion can't be done yet. The authors conclude the review with their own opinion. There are many encouraging data in patients with good clinical outcome after implantation of absorbable stents in more than 10 years follow-up.

  15. Three-year patient-related and stent-related outcomes of second-generation everolimus-eluting Xience V stents versus zotarolimus-eluting resolute stents in real-world practice (from the Multicenter Prospective EXCELLENT and RESOLUTE-Korea Registries).

    Science.gov (United States)

    Lee, Joo Myung; Park, Kyung Woo; Han, Jung-Kyu; Yang, Han-Mo; Kang, Hyun-Jae; Koo, Bon-Kwon; Bae, Jang-Whan; Woo, Sung-Il; Park, Jin Sik; Jin, Dong-Kyu; Jeon, Dong Woon; Oh, Seok Kyu; Park, Jong-Seon; Kim, Doo-Il; Hyon, Min Su; Jeon, Hui-Kyung; Lim, Do-Sun; Kim, Myeong-Gon; Rha, Seung-Woon; Her, Sung-Ho; Hwang, Jin-Yong; Kim, Sanghyun; Choi, Young Jin; Kang, Jin Ho; Moon, Keon-Woong; Jang, Yangsoo; Kim, Hyo-Soo

    2014-11-01

    Long-term outcomes are imperative to confirm safety of drug-eluting stents. There have been 2 randomized controlled trials comparing everolimus-eluting stents (EESs) and Resolute zotarolimus-eluting stents (ZES-Rs). To date, long-term clinical outcomes of these stents were limited to only 1 report, which has recently reported 4-year comparisons of these stents. Therefore, more evidence is needed regarding long-term clinical outcomes of the second-generation stents. This study compared the long-term clinical outcomes of EES with ZES-R in "all-comer" cohorts up to 3-year follow-up. The EXCELLENT and RESOLUTE-Korea registries prospectively enrolled 3,056 patients treated with EES and 1,998 with ZES-R, respectively, without exclusions. Stent-related composite outcomes (target lesion failure) and patient-related composite events up to 3-year follow-up were compared in crude and propensity score-matched analyses. Of 5,054 patients, 3,830 patients (75.8%) had off-label indication (2,217 treated with EES and 1,613 treated with ZES-R). The stent-related outcome (189 [6.2%] vs 127 [6.4%], p = 0.812) and the patient-related outcome (420 [13.7%] vs 250 [12.5%], p = 0.581) did not differ between EES and ZES-R, respectively, at 3 years, which was corroborated by similar results from the propensity score-matched cohort (hazard ratio [HR] 0.92, 95% confidence interval [CI] 0.70 to 1.20, p = 0.523 and 0.85, 95% CI 0.70 to 1.02, p = 0.081, for stent- and patient-related outcomes, respectively). The rate of definite or probable stent thrombosis up to 3 years (22 [0.7%] vs 10 [0.5%], p = 0.370) was also similar. The rate of very late definite or probable stent thrombosis was very low and comparable between the 2 stents (3 [0.1%] vs 1 [0.1%], p = 0.657). In multivariate analysis, chronic renal failure (adjusted HR 3.615, 95% CI 2.440 to 5.354, p stents showed comparable safety and efficacy at 3-year follow-up in this robust real-world registry with unrestricted use of EES and

  16. Clinical results with the Resolute zotarolimus-eluting stent in total coronary occlusions

    DEFF Research Database (Denmark)

    Kelbæk, Henning; Holmvang, Lene; Richardt, Gert

    2015-01-01

    Aims: We conducted a pooled post hoc analysis (RESOLUTE All Comers and RESOLUTE International) of patients who had the Resolute® zotarolimus-eluting stent (R-ZES) implanted in revascularised total occlusions (TO) compared with patients treated with R-ZES for non-occluded lesions. Methods and resu......Aims: We conducted a pooled post hoc analysis (RESOLUTE All Comers and RESOLUTE International) of patients who had the Resolute® zotarolimus-eluting stent (R-ZES) implanted in revascularised total occlusions (TO) compared with patients treated with R-ZES for non-occluded lesions. Methods...... lesion revascularisation) and Academic Research Consortium definite or probable stent thrombosis. The rate of TLF at two years was not significantly different among patients in the CTO (9.1%), TO (9.8%), and no occlusion (10.4%) groups (log-rank p=0.800); neither were the components of TLF. Definite...... or probable stent thrombosis occurred more frequently in the TO group (2.8% vs. 1.2% in the CTO and 1.1% in the group with no occlusion, p=0.027). There were 10 late and six very late stent thrombosis events. Conclusions: Apart from a higher rate of stent thrombosis in patients with TO, patients with totally...

  17. 2-year clinical outcomes after implantation of sirolimus-eluting, paclitaxel-eluting, and bare-metal coronary stents: results from the WDHR (Western Denmark Heart Registry)

    DEFF Research Database (Denmark)

    Kaltoft, Anne; Jensen, Lisette Okkels; Maeng, Michael

    2009-01-01

    OBJECTIVES: This registry study assessed the safety and efficacy of the 2 types of drug-eluting stents (DES), sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES), compared with bare-metal stents (BMS). BACKGROUND: Drug-eluting stents may increase the risk of stent thrombosis (ST...... databases. We used Cox regression analysis to control for confounding. RESULTS: The 2-year incidence of definite ST was 0.64% in BMS patients, 0.79% in DES patients (adjusted relative risk [RR]: 1.09; 95% confidence interval [CI]: 0.72 to 1.65), 0.50% in SES patients (adjusted RR: 0.63, 95% CI: 0.35 to 1...

  18. Comparison between Exclusive and Selective Drug-Eluting Stent Strategies in Treating Patients with Multivessel Coronary Artery Disease.

    Science.gov (United States)

    Tung, Ying-Chang; Hsiao, Ping-Gune; Hsu, Lung-An; Kuo, Chi-Tai; Chang, Chi-Jen

    2014-05-01

    The expanded usage of drug-eluting stents (DES) in treating patients with multivessel coronary artery disease (CAD) may sometimes be limited in real-world practice due to cost concerns. We compared the clinical outcomes of exclusive and selective DES use in treating patients with multivessel CAD. From November 2004 to December 2011, 110 patients with multivessel CAD who received four or more stents were enrolled into this study, and divided into two groups according to the DES strategy employed: exclusive DES (n = 52), or selective DES (n = 58). In the selective DES group, DES was reserved for complex lesions only, such that the incidence and predictors of clinical events were assessed. At a mean follow-up of 41.4 ± 26.5 months, there were no significant differences between the two strategies in terms of baseline characteristics, all-cause mortality (exclusive vs. selective: 1.9% vs. 6.9%, p = 0.21), cardiac death (1.9% vs. 1.7%, p = 0.94) and nonfatal myocardial infarction (3.8% vs. 5.2%, p = 0.74). Despite the presence of more ostial lesions in the exclusive DES group, there was a trend such that major adverse cardiac events (MACE) and target lesion revascularization (TLR) rates were higher in the selective DES group (MACE: 17.3% vs. 31%, p = 0.16; TLR: 11.5% vs. 24.1%, p = 0.08). The higher MACE rate in the selective DES group was mainly driven by a higher target vessel revascularization (TVR) rate (15.4% vs. 29.3%, p = 0.08). In the exclusive DES group, SYNTAX score was an independent predictor of MACE [Haxard ratio (HR): 1.09, 95% confidence internal (CI): 1.02-1.16, p = 0.01] and TVR (HR 1.08, 95% CI 1.01-1.15, p = 0.04). Compared to the exclusive DES strategy, the selective DES strategy with reservation of DES for complex lesions is associated with numerically higher, but not statistically significant, rates of MACE and all-cause mortality in this small group of patients with multivessel CAD receiving four or more stents. Bare metal stent; Drug-eluting

  19. Prognostic Value of Plasma Pentraxin-3 Levels in Patients with Stable Coronary Artery Disease after Drug-Eluting Stent Implantation

    Directory of Open Access Journals (Sweden)

    Liu Haibo

    2014-01-01

    Full Text Available Pentraxin-3 (PTX3 is an inflammatory marker thought to be more specific to cardiovascular inflammation than C-reactive protein (CRP. Our aim was to assess the prognostic value of PTX3 in patients with stable coronary artery disease (CAD after drug eluting stent (DES implantation. Plasma PTX3 levels were measured before percutaneous coronary intervention (PCI and at 24 h post-PCI in 596 consecutive patients with stable CAD. Patients were followed up for a median of 3 years (range 1–5 for major adverse cardiovascular events (MACEs. We found that the post-PCI plasma PTX3 levels were significantly higher at 24 h after PCI than pre-PCI, patients with MACEs had higher post-PCI PTX3 levels compared with MACEs-free patients, patients with higher post-PCI PTX3 levels (median > 4.384 ng/mL had a higher risk for MACEs than those with PTX3 < 4.384 ng/mL, and post-PCI PTX3, cTnI, multiple stents, and age but not high-sensitivity CRP (hsCRP were independently associated with the prevalence of MACEs after DES implantation. The present study shows that post-PCI PTX3 may be a more reliable inflammatory predictor of long-term MACEs in patients with stable CAD undergoing DES implantation than CRP. Measurement of post-PCI PTX3 levels could provide a rationale for risk stratification of patients with stable CAD after DES implantation.

  20. Direct comparison of coronary bare metal vs. drug-eluting stents: same platform, different mechanics?

    Science.gov (United States)

    Schmidt, Wolfram; Lanzer, Peter; Behrens, Peter; Brandt-Wunderlich, Christoph; Öner, Alper; Ince, Hüseyin; Schmitz, Klaus-Peter; Grabow, Niels

    2018-01-08

    Drug-eluting stents (DES) compared to bare metal stents (BMS) have shown superior clinical performance, but are considered less suitable in complex cases. Most studies do not distinguish between DES and BMS with respect to their mechanical performance. The objective was to obtain mechanical parameters for direct comparison of BMS and DES. In vitro bench tests evaluated crimped stent profiles, crossability in stenosis models, elastic recoil, bending stiffness (crimped and expanded), and scaffolding properties. The study included five pairs of BMS and DES each with the same stent platforms (all n = 5; PRO-Kinetic Energy, Orsiro: BIOTRONIK AG, Bülach, Switzerland; MULTI-LINK 8, XIENCE Xpedition: Abbott Vascular, Temecula, CA; REBEL Monorail, Promus PREMIER, Boston Scientific, Marlborough, MA; Integrity, Resolute Integrity, Medtronic, Minneapolis, MN; Kaname, Ultimaster: Terumo Corporation, Tokyo, Japan). Statistical analysis used pooled variance t tests for pairwise comparison of BMS with DES. Crimped profiles in BMS groups ranged from 0.97 ± 0.01 mm (PRO-Kinetic Energy) to 1.13 ± 0.01 mm (Kaname) and in DES groups from 1.02 ± 0.01 mm (Orsiro) to 1.13 ± 0.01 mm (Ultimaster). Crossability was best for low profile stent systems. Elastic recoil ranged from 4.07 ± 0.22% (Orsiro) to 5.87 ± 0.54% (REBEL Monorail) including both BMS and DES. The bending stiffness of crimped and expanded stents showed no systematic differences between BMS and DES neither did the scaffolding. Based on in vitro measurements BMS appear superior to DES in some aspects of mechanical performance, yet the differences are small and not class uniform. The data provide assistance in selecting the optimal system for treatment and assessment of new generations of bioresorbable scaffolds. not applicable.

  1. Telomerase Inhibition by Everolimus Suppresses Smooth Muscle Cell Proliferation and Neointima Formation Through Epigenetic Gene Silencing

    Directory of Open Access Journals (Sweden)

    Jun Aono, MD, PhD

    2016-01-01

    Full Text Available Proliferation of smooth muscle cells (SMCs during neointima formation is prevented by drug-eluting stents. The replicative capacity of mammalian cells is enhanced by telomerase expression; however, the contribution of telomerase to the proliferative response underlying neointima formation and its potential role as a pharmacological target are unknown. The present study investigated the mechanisms underlying the mitogenic function of telomerase, and tested the hypothesis that everolimus, which is commonly used on drug-eluting stents, suppresses SMC proliferation by targeting telomerase. Inhibition of neointima formation by everolimus was lost in mice overexpressing telomerase reverse transcriptase (TERT, indicating that repression of telomerase confers the anti-proliferative efficacy of everolimus. Everolimus reduced TERT expression in SMC through an Ets-1-dependent inhibition of promoter activation. The inhibition of TERT-dependent SMC proliferation by everolimus occurred in the absence of telomere shortening but rather as a result of a G1→S-phase arrest. Although everolimus failed to inhibit phosphorylation of the retinoblastoma protein as the gatekeeper of S-phase entry, it potently repressed downstream target genes. Chromatin immunoprecipitation assays demonstrated that TERT induced E2F binding to S-phase gene promoters and supported histone acetylation. These effects were sensitive to inhibition by everolimus. These results characterize telomerase as a previously unrecognized target for the antiproliferative activity of everolimus, and further identify a novel mitogenic pathway in SMC that depends on the epigenetic activation of S-phase gene promoters by TERT.

  2. Cost-effectiveness of drug-eluting stents versus bare-metal stents in patients undergoing percutaneous coronary intervention.

    Science.gov (United States)

    Baschet, Louise; Bourguignon, Sandrine; Marque, Sébastien; Durand-Zaleski, Isabelle; Teiger, Emmanuel; Wilquin, Fanny; Levesque, Karine

    2016-01-01

    To determine the cost-effectiveness of drug-eluting stents (DES) compared with bare-metal stents (BMS) in patients requiring a percutaneous coronary intervention in France, using a recent meta-analysis including second-generation DES. A cost-effectiveness analysis was performed in the French National Health Insurance setting. Effectiveness settings were taken from a meta-analysis of 117 762 patient-years with 76 randomised trials. The main effectiveness criterion was major cardiac event-free survival. Effectiveness and costs were modelled over a 5-year horizon using a three-state Markov model. Incremental cost-effectiveness ratios and a cost-effectiveness acceptability curve were calculated for a range of thresholds for willingness to pay per year without major cardiac event gain. Deterministic and probabilistic sensitivity analyses were performed. Base case results demonstrated that DES are dominant over BMS, with an increase in event-free survival and a cost-reduction of €184, primarily due to a diminution of second revascularisations, and an absence of myocardial infarction and stent thrombosis. These results are robust for uncertainty on one-way deterministic and probabilistic sensitivity analyses. Using a cost-effectiveness threshold of €7000 per major cardiac event-free year gained, DES has a >95% probability of being cost-effective versus BMS. Following DES price decrease, new-generation DES development and taking into account recent meta-analyses results, the DES can now be considered cost-effective regardless of selective indication in France, according to European recommendations.

  3. Efectos biológicos de los stents medicados en la circulación coronaria Biological effects of drug-eluting stents in the coronary circulation

    Directory of Open Access Journals (Sweden)

    Darío Echeverri

    2010-04-01

    Full Text Available Los stents medicados ofrecen la mejor alternativa disponible no quirúrgica para el tratamiento de la enfermedad coronaria gracias a su demostrada eficacia. Sin embargo, estos excelentes resultados han sido opacados en términos de seguridad, principalmente por la presencia de trombosis de stents de manera tardía o muy tardía. La comprensión de los efectos biológicos que ejercen a nivel de la arteria coronaria luego de su implante, se debe al efecto de la plataforma utilizada, el polímero y la droga que liberan. Los trastornos de reparación vascular inducidos favorecen la trombosis de stents y sus consecuencias clínicas. Se hace una revisión de los diferentes efectos biológicos de los stents medicados en las arterias coronarias, que permite comprender como han surgido rápidamente nuevas versiones en materiales, diseños, polímeros y medicamentos que reducen los efectos adversos a nivel coronario, mejorando su eficacia y seguridad.Drug-eluting stents offer the best available non-surgical alternative for the treatment of coronary disease, thanks to its demonstrated efficacy. However, in terms of security, these excellent results have been overshadowed by the late or very late appearance of stent thromboses.The biological effects they have in the coronary artery after its implantation are due to the effect of the platform used, the polymer and the medication released. The vascular healing disorders induced by drug-eluting stents favor stent thrombosis and its clinical consequences. This is a review of the different biological effects of drug-eluting stents in coronary arteries that allows to understand how the rapid onset of new versions of materials, designs, polymers and medications diminish adverse coronary effects and improve its efficacy and safety.

  4. Long-term prognostic value of risk scores after drug-eluting stent implantation for unprotected left main coronary artery: A pooled analysis of the ISAR-LEFT-MAIN and ISAR-LEFT-MAIN 2 randomized clinical trials.

    Science.gov (United States)

    Xhepa, Erion; Tada, Tomohisa; Kufner, Sebastian; Ndrepepa, Gjin; Byrne, Robert A; Kreutzer, Johanna; Ibrahim, Tareq; Tiroch, Klaus; Valgimigli, Marco; Tölg, Ralf; Cassese, Salvatore; Fusaro, Massimiliano; Schunkert, Heribert; Laugwitz, Karl L; Mehilli, Julinda; Kastrati, Adnan

    2017-01-01

    To evaluate the long-term prognostic value of risk scores in the setting of drug-eluting stent (DES) implantation for uLMCA. Data on the prognostic value of novel risk scores developed to select the most appropriate revascularization strategy in patients undergoing DES implantation for uLMCA disease are relatively limited. The study represents a patient-level pooled analysis of the ISAR-LEFT-MAIN (607 patients randomized to paclitaxel-eluting or sirolimus-eluting stents) and the ISAR-LEFT-MAIN-2 (650 patients randomized to everolimus-eluting or zotarolimus-eluting stents) randomized trials. The Syntax Score (SxScore) as well the Syntax Score II (SS-II), the EuroSCORE and the Global Risk Classification (GRC) were calculated. The primary outcome was all-cause mortality. At a mean follow-up of 3 years there were 160 deaths (12.7%). The death-incidence was significantly higher in the upper tertiles than in the intermediate or lower ones for all risk scores (log-rank test P risk scores were able to stratify the mortality risk at long-term follow-up. EuroSCORE was the only risk score that significantly improved the discriminatory power of a multivariable model to predict long-term mortality. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  5. Long-term Outcomes of Paclitaxel-Eluting Versus Sirolimus-Eluting Stent for Percutaneous Coronary Intervention: A Meta-Analysis

    International Nuclear Information System (INIS)

    Kong, J.; Liu, P.; Fan, X.; Wen, J.; Zhang, J.; Zhen, Y.; Li, J.; Cui, Y.; Zheng, X.; Ye, Z.

    2017-01-01

    The relative long-term efficacy and safety of sirolimus-eluting stents (SES) compared with paclitaxel-eluting stents (PES) in multiple comparative studies remains controversial. This report evaluates 29 randomized trials with 18,379 patients in whom long-term (more than 1 year) outcomes were evaluated. The primary outcomes were target lesion revascularization (TLR) and the secondary end points were death, cardiac death, myocardial infarction (MI), major adverse cardiac events (MACEs), target vessel revascularization (TVR)and stent thrombosis (ST). In comparison with PES, SES significantly reduced the long-term risk of TLR (RR=0.68; 95% CI=0.57 to 0.80, p<0.001), TVR (RR=0.69; 95% CI= 0.60 to 0.79, p<0.001) and MACE (RR=0.82; 95% CI= 0.77 to 0.88, p<0.001), while there were no significant difference with respect to death, cardiac death, MI and ST between the two groups. SES performance was significantly better for reducing the former three outcomes and comparable for the majority of the secondary end points when compared against PES. (author)

  6. Revascularisation versus medical treatment in patients with stable coronary artery disease: network meta-analysis

    Science.gov (United States)

    Stortecky, Stefan; Stefanini, Giulio G; daCosta, Bruno R; Rutjes, Anne Wilhelmina; Di Nisio, Marcello; Siletta, Maria G; Maione, Ausilia; Alfonso, Fernando; Clemmensen, Peter M; Collet, Jean-Philippe; Cremer, Jochen; Falk, Volkmar; Filippatos, Gerasimos; Hamm, Christian; Head, Stuart; Kappetein, Arie Pieter; Kastrati, Adnan; Knuuti, Juhani; Landmesser, Ulf; Laufer, Günther; Neumann, Franz-Joseph; Richter, Dimitri; Schauerte, Patrick; Sousa Uva, Miguel; Taggart, David P; Torracca, Lucia; Valgimigli, Marco; Wijns, William; Witkowski, Adam; Kolh, Philippe; Juni, Peter

    2014-01-01

    Objective To investigate whether revascularisation improves prognosis compared with medical treatment among patients with stable coronary artery disease. Design Bayesian network meta-analyses to combine direct within trial comparisons between treatments with indirect evidence from other trials while maintaining randomisation. Eligibility criteria for selecting studies A strategy of initial medical treatment compared with revascularisation by coronary artery bypass grafting or Food and Drug Administration approved techniques for percutaneous revascularization: balloon angioplasty, bare metal stent, early generation paclitaxel eluting stent, sirolimus eluting stent, and zotarolimus eluting (Endeavor) stent, and new generation everolimus eluting stent, and zotarolimus eluting (Resolute) stent among patients with stable coronary artery disease. Data sources Medline and Embase from 1980 to 2013 for randomised trials comparing medical treatment with revascularisation. Main outcome measure All cause mortality. Results 100 trials in 93 553 patients with 262 090 patient years of follow-up were included. Coronary artery bypass grafting was associated with a survival benefit (rate ratio 0.80, 95% credibility interval 0.70 to 0.91) compared with medical treatment. New generation drug eluting stents (everolimus: 0.75, 0.59 to 0.96; zotarolimus (Resolute): 0.65, 0.42 to 1.00) but not balloon angioplasty (0.85, 0.68 to 1.04), bare metal stents (0.92, 0.79 to 1.05), or early generation drug eluting stents (paclitaxel: 0.92, 0.75 to 1.12; sirolimus: 0.91, 0.75 to 1.10; zotarolimus (Endeavor): 0.88, 0.69 to 1.10) were associated with improved survival compared with medical treatment. Coronary artery bypass grafting reduced the risk of myocardial infarction compared with medical treatment (0.79, 0.63 to 0.99), and everolimus eluting stents showed a trend towards a reduced risk of myocardial infarction (0.75, 0.55 to 1.01). The risk of subsequent revascularisation was noticeably

  7. Long-termserial non-invasive multislice computed tomography angiography with functional evaluation after coronary implantation of a bioresorbable everolimus-eluting scaffold: the ABSORB cohort BMSCT substudy

    NARCIS (Netherlands)

    Onuma, Yoshinobu; Collet, Carlos; van Geuns, Robert-Jan; de Bruyne, Bernard; Christiansen, Evald; Koolen, Jacques; Smits, Pieter; Chevalier, Bernard; McClean, Dougal; Dudek, Dariusz; Windecker, Stephan; Meredith, Ian; Nieman, Koen; Veldhof, Susan; Ormiston, John; Serruys, Patrick W.

    2017-01-01

    Aims Multimodality invasive imaging of the first-in-man cohort demonstrated at 5 years stable lumen dimensions and a low rate of major adverse cardiac events (MACE). However, the long-term non-invasive assessment of this device remains to be documented. The objective was to describe the 72-month

  8. Anomalous Coronary Artery From the Opposite Sinus (ACAOS): Technical Challenges During Percutaneous Coronary Intervention.

    Science.gov (United States)

    Sinha, Santosh Kumar; Razi, Mahmodula; Mahrotra, Anupam; Aggarwal, Puneet; Singh, Anupam; Rekwal, Lokendra; Tripathi, Sunil; Abhishekh, Nishant Kumar; Krishna, Vinay

    2018-04-01

    Anomalies of the coronary arteries are reported in 1-2% of patients among diagnostic angiogram. Ectopic origin of right coronary artery (RCA) from opposite sinus is one of the most common and they are mainly benign, but at times may be malignant. We report a case of a 69-year-old male who underwent early invasive percutaneous coronary intervention for non-ST-segment elevation myocardial infarction (NSTEMI) where RCA arising from left sinus at the root of left main artery was culprit and various technical challenges were encountered while intervening in form of cannulation to tracking of hardwares. RCA was cannulated with floating wire technique using hockey stick guide catheter and revascularized by deployment of 3.5 × 38 mm Promus Premier Everolimus eluting stent (Boston Scientific, USA). To the best of our knowledge, this is the first ever report of ectopic RCA being revascularized by using hockey stick catheter.

  9. Nine-month Angiographic and Two-year Clinical Follow-up of Novel Biodegradable-polymer Arsenic Trioxide-eluting Stent Versus Durable-polymer Sirolimus-eluting Stent For Coronary Artery Disease

    Directory of Open Access Journals (Sweden)

    Li Shen

    2015-01-01

    Full Text Available Background: Despite great reduction of in-stent restenosis, first-generation drug-eluting stents (DESs have increased the risk of late stent thrombosis due to delayed endothelialization. Arsenic trioxide, a natural substance that could inhibit cell proliferation and induce cell apoptosis, seems to be a promising surrogate of sirolimus to improve DES performance. This randomized controlled trial was to evaluate the efficacy and safety of a novel arsenic trioxide-eluting stent (AES, compared with traditional sirolimus-eluting stent (SES. Methods: Patients with symptoms of angina pectoris were enrolled and randomized to AES or SES group. The primary endpoint was target vessel failure (TVF, and the second endpoint includes rates of all-cause death, cardiac death or myocardial infarction, target lesion revascularization (TLR by telephone visit and late luminal loss (LLL at 9-month by angiographic follow-up. Results: From July 2007 to 2009, 212 patients were enrolled and randomized 1:1 to receive either AES or SES. At 2 years of follow-up, TVF rate was similar between AES and SES group (6.67% vs. 5.83%, P = 0.980. Frequency of all-cause death was significantly lower in AES group (0 vs. 4.85%, P = 0.028. There was no significant difference between AES and SES in frequency of TLR and in-stent restenosis, but greater in-stent LLL was observed for AES group (0.29 ± 0.52 mm vs. 0.10 ± 0.25 mm, P = 0.008. Conclusions: After 2 years of follow-up, AES demonstrated comparable efficacy and safety to SES for the treatment of de novo coronary artery lesions.

  10. Five-year outcome after implantation of zotarolimus- and everolimus-eluting stents in randomized trial participants and nonenrolled eligible patients : A secondary analysis of a randomized clinical trial

    NARCIS (Netherlands)

    Von Birgelen, Clemens; Van Der Heijden, Liefke C.; Basalus, Mounir Welson Zakhary; Kok, Marlies M.; Sen, Hanim; Louwerenburg, Hans W.; van Houwelingen, Gert K.; Stoel, Martin G.; de Man, Frits H.A.F.; Linssen, Gerard C.M.; Tandjung, Kenneth; Doggen, Carine J.M.; Van Der Palen, Job; Löwik, Marije M.

    2017-01-01

    IMPORTANCE: Long-term follow-up after a clinical trial of 2 often-used, newer-generation drug-eluting stents (DESs) in a broad patient population is of interest. Comprehensive long-term outcome of eligible nonenrolled patients has never been reported. OBJECTIVE: To assess 5-year safety and efficacy

  11. Direct implantation of rapamycin-eluting stents with bioresorbable drug carrier technology utilising the Svelte coronary stent-on-a-wire: the DIRECT II study.

    Science.gov (United States)

    Verheye, Stefan; Khattab, Ahmed A; Carrie, Didier; Stella, Pieter; Slagboom, Ton; Bartunek, Jozef; Onuma, Yoshinobu; Serruys, Patrick W

    2016-08-05

    Our aim was to demonstrate the safety and efficacy of the Svelte sirolimus-eluting coronary stent-on-a-wire Integrated Delivery System (IDS) with bioresorbable drug coating compared to the Resolute Integrity zotarolimus-eluting stent with durable polymer in patients with de novo coronary artery lesions. Direct stenting, particularly in conjunction with transradial intervention (TRI), has been associated with reduced bleeding complications, procedure time, radiation exposure and contrast administration compared to conventional stenting with wiring and predilatation. The low-profile Svelte IDS is designed to facilitate TRI and direct stenting, reducing the number of procedural steps, time and cost associated with coronary stenting. DIRECT II was a prospective, multicentre trial which enrolled 159 patients to establish non-inferiority of the Svelte IDS versus Resolute Integrity using a 2:1 randomisation. The primary endpoint was angiographic in-stent late lumen loss (LLL) at six months. Target vessel failure (TVF), as well as secondary clinical endpoints, will be assessed annually up to five years. At six months, in-stent LLL was 0.09±0.31 mm in the Svelte IDS group compared to 0.13±0.27 mm in the Resolute Integrity group (p<0.001 for non-inferiority). TVF at one year was similar across the Svelte IDS and Resolute Integrity groups (6.5% vs. 9.8%, respectively). DIRECT II demonstrated the non-inferiority of the Svelte IDS to Resolute Integrity with respect to in-stent LLL at six months. Clinical outcomes at one year were comparable between the two groups.

  12. A prospective evaluation of the safety and efficacy of the TAXUS Element paclitaxel-eluting coronary stent system for the treatment of de novo coronary artery lesions: Design and statistical methods of the PERSEUS clinical program

    Directory of Open Access Journals (Sweden)

    Wehrenberg Scott

    2010-01-01

    Full Text Available Abstract Background Paclitaxel-eluting stents decrease angiographic and clinical restenosis following percutaneous coronary intervention compared to bare metal stents. TAXUS Element is a third-generation paclitaxel-eluting stent which incorporates a novel, thinner-strut, platinum-enriched metal alloy platform. The stent is intended to have enhanced radiopacity and improved deliverability compared to other paclitaxel-eluting stents. The safety and efficacy of the TAXUS Element stent are being evaluated in the pivotal PERSEUS clinical trials. Methods/Design The PERSEUS trials include two parallel studies of the TAXUS Element stent in single, de novo coronary atherosclerotic lesions. The PERSEUS Workhorse study is a prospective, randomized (3:1, single-blind, non-inferiority trial in subjects with lesion length ≤28 mm and vessel diameter ≥2.75 mm to ≤4.0 mm which compares TAXUS Element to the TAXUS Express2 paclitaxel-eluting stent system. The Workhorse study employs a novel Bayesian statistical approach that uses prior information to limit the number of study subjects exposed to the investigational device and thus provide a safer and more efficient analysis of the TAXUS Element stent. PERSEUS Small Vessel is a prospective, single-arm, superiority trial in subjects with lesion length ≤20 mm and vessel diameter ≥2.25 mm to Discussion The TAXUS PERSEUS clinical trial program uses a novel statistical approach to evaluate whether design and metal alloy iterations in the TAXUS Element stent platform provide comparable safety and improved procedural performance compared to the previous generation Express stent. PERSEUS trial enrollment is complete and primary endpoint data are expected in 2010. PERSEUS Workhorse and Small Vessel are registered at http://www.clinicaltrials.gov, identification numbers NCT00484315 and NCT00489541.

  13. Telomerase Inhibition by Everolimus Suppresses Smooth Muscle Cell Proliferation and Neointima Formation Through Epigenetic Gene Silencing.

    Science.gov (United States)

    Aono, Jun; Ruiz-Rodriguez, Ernesto; Qing, Hua; Findeisen, Hannes M; Jones, Karrie L; Heywood, Elizabeth B; Bruemmer, Dennis

    2016-01-01

    The present study sought to investigate the mechanisms underlying the mitogenic function of telomerase and to test the hypothesis that everolimus, commonly used on drug-eluting stents, suppresses smooth muscle cells (SMC) proliferation by targeting telomerase. Proliferation of SMC during neointima formation is prevented by drug-eluting stents. Although the replicative capacity of mammalian cells is enhanced by telomerase expression, the contribution of telomerase to the proliferative response underlying neointima formation and its potential role as a pharmacological target remain to be investigated. We first employed constitutive expression of telomerase reverse transcriptase (TERT) in cell systems to study transcriptional mechanisms by which telomerase activates a mitogenic program. Second, overexpression of telomerase in mice provided a model to study the role of telomerase as a drug target for the antiproliferative efficacy of everolimus. Inhibition of neointima formation by everolimus is lost in mice overexpressing TERT, indicating that repression of telomerase confers the antiproliferative efficacy of everolimus. Everolimus reduces TERT expression in SMC through an Ets-1-dependent inhibition of promoter activation. The inhibition of TERT-dependent SMC proliferation by everolimus occurred in the absence of telomere shortening but rather as a result of a G1→S phase arrest. Although everolimus failed to inhibit phosphorylation of the retinoblastoma protein as the gatekeeper of S-phase entry, it potently repressed downstream target genes. Using chromatin immunoprecipitation assays, we finally demonstrate that TERT induces E2F binding to S-phase gene promoters and supports histone acetylation, effects that are inhibited by everolimus and mediate its antiproliferative activity. These results characterize telomerase as a previously unrecognized target for the antiproliferative activity of everolimus. Our studies further identify a novel mitogenic pathway in SMC

  14. Coronary Stents in Diabetic Patients: State of the Knowledge.

    Science.gov (United States)

    Codner, Pablo; Gurm, Hitinder Singh; Motivala, Apurva

    2017-04-01

    This review article aims to summarize the findings of the most relevant research that compared the use of paclitaxel vs. "limus" based drug eluting stent (DES) in diabetic patients and to define the current state of knowledge with new stent technologies in this patient population. Since drug eluting stents (DES) were introduced, it has been of great interest to establish whether paclitaxel or sirolimus eluting stents have the same safety and efficacy features for patients with coronary artery disease. The answer to this question is particularly relevant for diabetic patients. Several randomized trials, registry-based studies, and meta-analyses have assessed the performance of these different DES in diabetic patients. The most recently published data favors limus over paclitaxel DES in diabetic patients, but most of these studies compared first vs. second generation DES with the inherent caveats of comparing different platforms, alloys, and drug delivery vehicles. In this literature review, we found that there is robust evidence favoring the use of DES over bare metal stents in diabetic patients with coronary artery disease. We also found that the current state of knowledge is that the everolimus eluting stents have better safety and efficacy than paclitaxel eluting stents in diabetic patients and hence should be the preferred choice. New revascularization strategies including bio-absorbable scaffolds, polymer free stents, and bio-degradable polymers are being studied in diabetic patients with encouraging results.

  15. Incidence of definite stent thrombosis or in-stent restenosis after drug-eluting stent implantation for treatment of coronary in-stent restenosis. From western denmark heart registry

    DEFF Research Database (Denmark)

    Jensen, Jesper; Jensen, Lisette Okkels; Terkelsen, Christian Juhl

    2012-01-01

    There are limited data on the optimal management of in-stent restenosis after percutaneous coronary intervention (PCI) with bare metal stent (BMS) or drug-eluting stent (DES) implantations. We assessed the clinical presentation, the incidence, and prognosis of definite stent thrombosis...

  16. Novel management strategy for coronary steal syndrome: case report of occlusion of a LIMA graft side branch with a combination of drug-eluting and covered-stent deployment.

    LENUS (Irish Health Repository)

    Hynes, Brian G

    2009-11-01

    We report a novel percutaneous therapeutic approach to the management of suspected coronary artery steal syndrome resulting from a large side branch of the left internal mammary artery bypass graft, using a combination of coated and drug-eluting stents. We demonstrate the feasibility and long-term efficacy of this strategy in a case report.

  17. In-Stent Restenosis of Drug-Eluting Stents Compared With a Matched Group of Patients With De Novo Coronary Artery Stenosis.

    Science.gov (United States)

    Buchanan, Kyle D; Torguson, Rebecca; Rogers, Toby; Xu, Linzhi; Gai, Jiaxiang; Ben-Dor, Itsik; Suddath, William O; Satler, Lowell F; Waksman, Ron

    2018-03-13

    Drug-eluting stents (DES) significantly reduced the incidence of in-stent restenosis (ISR). However, ISR still exists in the contemporary DES era. Previously deemed to be a benign process, ISR leads to complex presentation and intervention. This study aimed to compare the presentation and outcome of DES-ISR versus de novo lesions. We performed a retrospective analysis of 11,666 patients receiving percutaneous coronary intervention from 2003 to 2017 and divided them into 2 groups by de novo stenosis and ISR. They were matched based on common cardiovascular risk factors at a 4:1 ratio, respectively. After matching, a total of 1,888 patients with 3,126 de novo lesions and 472 patients with 508 ISR lesions were analyzed. Patients with ISR presented more often with unstable angina (61% vs 45%, p stent technique and should motivate the continued development of fully bioresorbable scaffolds. Copyright © 2018 Elsevier Inc. All rights reserved.

  18. Effects of everolimus on macrophage-derived foam cell behavior

    International Nuclear Information System (INIS)

    Hsu, Steven; Koren, Eugen; Chan, Yen; Koscec, Mirna; Sheehy, Alexander; Kolodgie, Frank; Virmani, Renu; Feder, Debra

    2014-01-01

    Purpose: The purpose of this study was to investigate the effects of everolimus on foam cell (FC) viability, mRNA levels, and inflammatory cytokine production to better understand its potential inhibitory effects on atheroma progression. Methods and materials: Human THP1 macrophage-derived FC were formed using acetylated LDL (acLDL, 100 μg/mL) for 72 hours, followed by everolimus treatment (10 -5 –10 -11 M) for 24 hours. FC viability was quantified using fluorescent calcein AM/DAPI staining. FC lysates and media supernatants were analyzed for apoptosis and necrosis using a Cell Death ELISA PLUS assay. FC lysates and media supernatants were also analyzed for inflammatory cytokine (IL1β, IL8, MCP1, TNFα) mRNA levels and protein expression using quantitative reverse transcription real-time polymerase chain reaction (QPCR) and a Procarta® immunoassay, respectively. mRNA levels of autophagy (MAP1LC3), apoptosis (survivin, clusterin), and matrix degradation (MMP1, MMP9) markers were evaluated by Quantigene® Plex assay and verified with QPCR. Additionally, hypercholesterolemic rabbits received everolimus-eluting stents (EES) for 28 or 60 days. RAM-11 immunohistochemical staining was performed to compare %RAM-11 positive area between stented sections and unstented proximal sections. Statistical significance was calculated using one-way ANOVA (p ≤ 0.05). Results: Calcein AM/DAPI staining showed that FC exposed to everolimus (10 -5 M) had significantly decreased viability compared to control. FC apoptosis was significantly increased at a high dose of everolimus (10 -5 M), with no necrotic effects at any dose tested. Everolimus did not affect endothelial (HUVEC) and smooth muscle (HCASMC) cell apoptosis or necrosis. Everolimus (10 -5 M) significantly increased MAP1LC3, caused an increased trend in clusterin (p = 0.10), and significantly decreased survivin and MMP1 mRNA levels in FC. MCP1 cytokine mRNA levels and secreted protein expression was significantly decreased

  19. Effects of everolimus on macrophage-derived foam cell behavior

    Energy Technology Data Exchange (ETDEWEB)

    Hsu, Steven, E-mail: steven.hsu@av.abbott.com [Abbott Vascular, 3200 Lakeside Drive, Santa Clara, CA 95054 (United States); Koren, Eugen; Chan, Yen; Koscec, Mirna; Sheehy, Alexander [Abbott Vascular, 3200 Lakeside Drive, Santa Clara, CA 95054 (United States); Kolodgie, Frank; Virmani, Renu [CVPath Institute, Inc., 19 Firstfield Road, Gaithersburg, MD 20878 (United States); Feder, Debra [Abbott Vascular, 3200 Lakeside Drive, Santa Clara, CA 95054 (United States)

    2014-07-15

    Purpose: The purpose of this study was to investigate the effects of everolimus on foam cell (FC) viability, mRNA levels, and inflammatory cytokine production to better understand its potential inhibitory effects on atheroma progression. Methods and materials: Human THP1 macrophage-derived FC were formed using acetylated LDL (acLDL, 100 μg/mL) for 72 hours, followed by everolimus treatment (10{sup -5}–10{sup -11} M) for 24 hours. FC viability was quantified using fluorescent calcein AM/DAPI staining. FC lysates and media supernatants were analyzed for apoptosis and necrosis using a Cell Death ELISA{sup PLUS} assay. FC lysates and media supernatants were also analyzed for inflammatory cytokine (IL1β, IL8, MCP1, TNFα) mRNA levels and protein expression using quantitative reverse transcription real-time polymerase chain reaction (QPCR) and a Procarta® immunoassay, respectively. mRNA levels of autophagy (MAP1LC3), apoptosis (survivin, clusterin), and matrix degradation (MMP1, MMP9) markers were evaluated by Quantigene® Plex assay and verified with QPCR. Additionally, hypercholesterolemic rabbits received everolimus-eluting stents (EES) for 28 or 60 days. RAM-11 immunohistochemical staining was performed to compare %RAM-11 positive area between stented sections and unstented proximal sections. Statistical significance was calculated using one-way ANOVA (p ≤ 0.05). Results: Calcein AM/DAPI staining showed that FC exposed to everolimus (10{sup -5} M) had significantly decreased viability compared to control. FC apoptosis was significantly increased at a high dose of everolimus (10{sup -5} M), with no necrotic effects at any dose tested. Everolimus did not affect endothelial (HUVEC) and smooth muscle (HCASMC) cell apoptosis or necrosis. Everolimus (10{sup -5} M) significantly increased MAP1LC3, caused an increased trend in clusterin (p = 0.10), and significantly decreased survivin and MMP1 mRNA levels in FC. MCP1 cytokine mRNA levels and secreted protein

  20. Impact of Hemoglobin A1c Levels on Residual Platelet Reactivity and Outcomes After Insertion of Coronary Drug-Eluting Stents (from the ADAPT-DES Study)

    DEFF Research Database (Denmark)

    Schoos, Mikkel M.; Dangas, George D.; Mehran, Roxana

    2016-01-01

    An increasing hemoglobin A1c (HbA1c) level portends an adverse cardiovascular prognosis; however, the association between glycemic control, platelet reactivity, and outcomes after percutaneous coronary intervention (PCI) with drug-eluting stents (DES) is unknown. We sought to investigate whether Hb...... With Drug Eluting Stents registry, HbA1c levels were measured as clinically indicated in 1,145 of 8,582 patients, stratified by HbA1c 8.5% (n = 171, 14.9%). HPR on clopidogrel and aspirin was defined after PCI as P2Y12 reaction units (PRU) >208...... >208 (42.5%, 50.2%, and 62.3%, p definite or probable stent thrombosis (ST; 0.9%, 2.7%, and 4.2%, p = 0.02) increased progressively with HbA1c groups. Clinically relevant bleeding was greatest in the intermediate HbA1c group (8.2% vs 13.1% vs 9.5%, p = 0.04). In adjusted models...

  1. Prasugrel vs. clopidogrel in contemporary Western European patients with acute coronary syndromes receiving drug-eluting stents

    DEFF Research Database (Denmark)

    Wein, Bastian; Coslovsky, Michael; Jabbari, Reza

    2017-01-01

    BACKGROUND: Clinical and cost-effectiveness of prasugrel vs. clopidogrel in acute coronary syndrome (ACS) was only evaluated using TRITON-TIMI 38 event rates. A comparative analysis of both drugs in contemporary European ACS patients is lacking. METHODS: To address this issue, cardiac and bleedin......=0.255), but more major bleedings (4.0% vs. 1.7%, pexpenditures per patient: 1116.3 (DNK), 1063.5 (GER) and 880.8 (SUI) EURO, respectively. Accordingly, incremental cost...

  2. Safety and efficacy of limus-eluting stents and balloon angioplasty for sirolimus-eluting in-stent restenosis

    Energy Technology Data Exchange (ETDEWEB)

    Ota, Hideaki [Division of Interventional Cardiology, MedStar Washington Hospital Center, Washington, DC 20010 (United States); Mahmoudi, Michael [University of Surrey, Guildford Road, Surrey, GU2-7XH (United Kingdom); Kitabata, Hironori; Torguson, Rebecca; Chen, Fang; Satler, Lowell F.; Suddath, William O.; Pichard, Augusto D. [Division of Interventional Cardiology, MedStar Washington Hospital Center, Washington, DC 20010 (United States); Waksman, Ron, E-mail: ron.waksman@medstar.net [Division of Interventional Cardiology, MedStar Washington Hospital Center, Washington, DC 20010 (United States)

    2015-03-15

    Objectives: The aim of this study was to compare the safety and efficacy of everolimus-eluting stent (EES), sirolimus-eluting stent (SES), and plain old balloon angioplasty (POBA) for the treatment of SES in-stent restenosis (S-ISR). Background: The optimal treatment for drug-eluting in-stent restenosis remains controversial. Methods: The study cohort comprised 310 consecutive patients (444 lesions) who presented with S-ISR to our institution and underwent treatment with EES (43 patients), SES (102), or POBA (165). The analyzed clinical parameters were the 1-year rates of death, Q-wave myocardial infarction (MI), target lesion revascularization (TLR), target vessel revascularization (TVR), definite stent thrombosis (ST) and major adverse cardiac event (MACE) defined as the composite of death, MI, or TLR at 1-year. Results: The three groups were well matched for the conventional risk factors for coronary artery disease except for smoking. The 1-year analyzed clinical parameters were similar in the three groups: MACE (EES = 14%, SES = 18%, POBA = 20%; p = 0.65), death (EES = 2.3%, SES = 6.2%, POBA = 6.1%; p = 0.61), MI (EES = 4.8%, SES = 2.1%, POBA = 2.5%; p = 0.69), TLR (EES = 11.9%, SES = 12.1%, POBA = 24%; p = 0.78), and TVR (EES = 11.9%, SES = 24.8%, POBA = 22.2%; p = 0.23). There were no cases of definite ST. MACE-free rate was significantly lower in patients with recurrent in-stent restenosis (log-rank p = 0.006). Presentation with acute MI, number of treated lesions and a previous history of MI were found to be independent predictors of MACE. Conclusions: In patients presenting with S-ISR, treatment with implantation of an EES, SES, or POBA is associated with similar clinical outcomes. Patients presenting with recurrent ISR may have a poorer clinical outcome.

  3. A prospective, multicenter, post marketing surveillance study to evaluate the safety and effectiveness of the Superia-Sirolimus Eluting Coronary Stent System (SSECSS) implanted during routine clinical practice in India.

    Science.gov (United States)

    Chandra, Praveen; Kumar, Tarun

    2014-01-01

    A prospective, multicenter, post marketing surveillance study to evaluate the safety and effectiveness of the Superia-Sirolimus Eluting Coronary Stent System (SSECSS) implanted during routine clinical practice in India. 1. To study the MACE and in stent and In-segment Loss at Six Months (in a pre selected group of 50 patients). 1. Clinical and procedural success. This is a prospective, open label, single-arm, multicenter (16 sites), post marketing observational study enrolling patients implanted with Superia-Sirolimus Eluting Coronary Stent (SSECS) in routine clinical practice in India. A total of 200 Patients of coronary Artery Disease (CAD) implanted with Superia-Sirolimus Eluting Coronary Stent (SSECS) were enrolled. Clinical assessments were done at 30 days, 180 days and at 1, 2 years either telephonically or office visit. A cohort of 50 pre-selected patients were followed up for angiographic evaluation at 180 days. MACE at 12 month of follow up was 1.71%.Late lumen loss, in segment was 0.14 and in stent was 0.10 mm at 6 month of follow-up. TLR was required only in 2 patients. Superia stent is as safe as other biodegradable polymer stent in the market and time has come for biodegradable polymer stent with thin struts. Copyright © 2014 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.

  4. Heparin monotherapy or bivalirudin during percutaneous coronary intervention in patients with non-ST-segment-elevation acute coronary syndromes or stable ischemic heart disease: results from the Evaluation of Drug-Eluting Stents and Ischemic Events registry.

    Science.gov (United States)

    Bangalore, Sripal; Pencina, Michael J; Kleiman, Neal S; Cohen, David J

    2014-06-01

    The use of bivalirudin versus unfractionated heparin monotherapy in patients without ST-segment-elevation myocardial infarction is not well defined. The study population consisted of patients enrolled in the Evaluation of Drug-Eluting Stents and Ischemic Events (EVENT) registry with either non-ST-segment-elevation acute coronary syndromes or stable ischemic heart disease, who underwent percutaneous coronary intervention with either unfractionated heparin or bivalirudin monotherapy. Propensity score matching was used to adjust for baseline characteristics. The primary bleeding (in-hospital composite bleeding-access site bleeding, thrombolysis in myocardial infarction major/minor bleeding, or transfusion) and primary (in-hospital death/myocardial infarction) and secondary ischemic outcomes (death/myocardial infarction/unplanned repeat revascularization at 12 months) were evaluated. Propensity score matching yielded 1036 patients with non-ST-segment-elevation acute coronary syndromes and 2062 patients with stable ischemic heart disease. For the non-ST-segment-elevation acute coronary syndrome cohort, bivalirudin use was associated with lower bleeding (difference, -3.3% [-0.8% to -5.8%]; P=0.01; number need to treat=30) without increase in either primary (difference, 1.2% [4.1% to -1.8%]; P=0.45) or secondary ischemic outcomes, including stent thrombosis (difference, 0.0% [1.3% to -1.3%]; P=1.00). Similarly, in the stable ischemic heart disease cohort, bivalirudin use was associated with lower bleeding (difference, -1.8% [-0.4% to -3.3%]; P=0.01; number need to treat=53) without increase in either primary (difference, 0.4% [2.3% to -1.5%]; P=0.70) or secondary ischemic outcomes, including stent thrombosis (difference, 0.0% [0.7% to -0.7%]; P=1.00) when compared with unfractionated heparin monotherapy. Among patients with non-ST-segment-elevation acute coronary syndromes or stable ischemic heart disease undergoing percutaneous coronary intervention, bivalirudin use

  5. Comparison of a Simple Angiographic Approach With a Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery Score-Based Approach for Left Main Coronary Artery Stenting: A Pooled Analysis of Serial PRECOMBAT (Premier of Randomized Comparison of Bypass Surgery Versus Angioplasty Using Sirolimus-Eluting Stent in Patients With Left Main Coronary Artery Disease) Studies.

    Science.gov (United States)

    Lee, Pil Hyung; Lee, Jong-Young; Lee, Cheol Whan; Kim, Seon-Ok; Ahn, Jung-Min; Park, Duk-Woo; Kang, Soo-Jin; Lee, Seung-Whan; Kim, Young-Hak; Park, Seong-Wook; Park, Seung-Jung

    2018-01-01

    The applicability of Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery scores to left main coronary artery disease (CAD) has been questioned. A simplified alternative is needed for guiding decision making. We evaluated the prognostic value of a simplified angiographic classification in comparison with a Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery score-based approach for patients with left main CAD undergoing drug-eluting stent implantation. The proposed approach classified left main CAD as either extensive (n=819), defined as left main bifurcation lesions with an involvement of ostial left circumflex artery or as any left main lesion plus multivessel CAD, or limited (n=453), defined as ostial/midshaft lesions or left main bifurcation lesions without an involvement of ostium of left circumflex artery, alone or plus 1-vessel disease. The databases from 4 prospective Premier of Randomized Comparison of Bypass Surgery versus Angioplasty Using Sirolimus-Eluting Stent in Patients with Left Main Coronary Artery Disease studies were pooled, and the primary outcome was a major adverse cardiac event, defined as death, myocardial infarction, or repeat revascularization. During follow-up (median 38 months; interquartile range, 36-61 months), the risk for major adverse cardiac event was significantly higher with extensive than with limited left main CAD (adjusted hazard ratio, 2.13; 95% confidence interval, 1.54-2.94; P Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery score tertiles did not effectively stratify these 2 outcome measures. Compared with Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery scores, the simpler angiographic approach provided better discrimination for future cardiovascular events in patients with left main CAD undergoing drug-eluting stent implantation. © 2018 American Heart Association, Inc.

  6. Stent Thrombosis With Drug-Eluting Stents and Bioresorbable Scaffolds: Evidence From a Network Meta-Analysis of 147 Trials.

    Science.gov (United States)

    Kang, Si-Hyuck; Chae, In-Ho; Park, Jin-Joo; Lee, Hak Seung; Kang, Do-Yoon; Hwang, Seung-Sik; Youn, Tae-Jin; Kim, Hyo-Soo

    2016-06-27

    This study sought to perform a systematic review and network meta-analysis to compare the relative safety and efficacy of contemporary DES and BVS. To improve outcomes of patients undergoing percutaneous coronary revascularization, there have been advances in the design of drug-eluting stents (DES), including the development of drug-eluting bioresorbable vascular scaffolds (BVS). Prospective, randomized, controlled trials comparing bare-metal stents (BMS), paclitaxel-eluting stents (PES), sirolimus-eluting stents (SES), Endeavor zotarolimus-eluting stents (E-ZES), cobalt-chromium (CoCr) everolimus-eluting stents (EES), platinum-chromium (PtCr)-EES, biodegradable polymer (BP)-EES, Resolute zotarolimus-eluting stents (R-ZES), BP biolimus-eluting stents (BP-BES), hybrid sirolimus-eluting stents (H [Orsiro]-SES), polymer-free sirolimus- and probucol-eluting stents, or BVS were searched in online databases. The primary endpoint was definite or probable stent thrombosis at 1 year. A total of 147 trials including 126,526 patients were analyzed in this study. All contemporary DES were superior to BMS and PES in terms of definite or probable stent thrombosis at 1 year. CoCr-EES, PtCr-EES, and H-SES were associated with significantly lower risk than BVS. CoCr-EES and H-SES were superior to SES and BP-BES. The risk of myocardial infarction was significantly lower with H-SES than with BVS. There were no significant differences regarding all-cause or cardiac mortality. Contemporary devices including BVS showed comparably low risks of repeat revascularization. Contemporary DES, including biocompatible DP-DES, BP-DES, and polymer-free DES, showed a low risk of definite or probable stent thrombosis at 1 year. BVS had an increased risk of device thrombosis compared with CoCr-EES, PtCr-EES, and H-SES. Data from extended follow-up are warranted to confirm the long-term safety of contemporary coronary devices. Copyright © 2016 American College of Cardiology Foundation. Published by

  7. 10-Year Clinical Outcome After Randomization to Treatment by Sirolimus- or Paclitaxel-Eluting Coronary Stents

    DEFF Research Database (Denmark)

    Galløe, Anders M; Kelbæk, Henning; Thuesen, Leif

    2017-01-01

    of patients included in a large randomized trial for 10 years to enable detection of late changes in annual event rates that could necessitate medical attention. METHODS: A total of 2,098 unselected all-comer patients (50% with acute coronary syndrome) were randomly assigned to have a first-generation DES...... for both stent types, with no apparent late changes. Although there is no need for extraordinary medical attention for these patients, the absence of declines in annual event rates calls for continuous surveillance. (Danish Organization on Randomized Trials With Clinical Outcome II [SORT OUT II]; NCT...

  8. Long term outcomes of new generation drug eluting stents versus coronary artery bypass grafting for multivessel and/or left main coronary artery disease. A Bayesian network meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Mina, George S; Watti, Hussam; Soliman, Demiana; Shewale, Anand; Atkins, Jessica; Reddy, Pratap; Dominic, Paari

    2018-01-05

    Most data guiding revascularization of multivessel disease (MVD) and/or left main disease (LMD) favor coronary artery bypass grafting (CABG) over percutaneous coronary intervention (PCI). However, those data are based on trials comparing CABG to bare metal stents (BMS) or old generation drug eluting stents (OG-DES). Hence, it is essential to outcomes of CABG to those of new generation drug eluting stents (NG-DES). We searched PUBMED and Cochrane database for trials evaluating revascularization of MVD and/or LMD with CABG and/or PCI. A Bayesian network meta-analysis was performed to calculate odds ratios (OR) and 95% credible intervals (CrI). Primary outcome was major adverse cardiovascular events (MACE) at 3-5 years. Secondary outcomes were mortality, cerebrovascular accidents (CVA), myocardial infarction (MI) and repeat revascularization. We included 10 trials with a total of 9287 patients. CABG was associated with lower MACE when compared to BMS or OG-DES. However, MACE was not significantly different between CABG and NG-DES (OR 0.79, CrI 0.45-1.40). Moreover, there were no significant differences between CABG and NG-DES in mortality (OR 0.78, CrI 0.45-1.37), CVA (OR 0.93 CrI 0.35-2.2) or MI (OR 0.6, CrI 0.17-2.0). On the other hand, CABG was associated with lower repeat revascularization (OR 0.55, CrI 0.36-0.84). Our study suggests that NG-DES is an acceptable alternative to CABG in patients with MVD and/or LMD. However, repeat revascularization remains to be lower with CABG than with PCI. Copyright © 2018. Published by Elsevier Inc.

  9. Recurrent post-partum coronary artery dissection

    Directory of Open Access Journals (Sweden)

    Resnic Frederic S

    2010-10-01

    Full Text Available Abstract Coronary artery dissection is a rare but well-described cause for myocardial infarction during the post-partum period. Dissection of multiple coronary arteries is even less frequent. Here we present a case of recurrent post-partum coronary artery dissections. This unusual presentation poses unique problems for management. A 35 year-old female, gravida 3 para 2, presented with myocardial infarction 9 weeks and 3 days post-partum. Cardiac catheterization demonstrated left anterior descending (LAD dissection but an otherwise normal coronary anatomy. The lesion was treated with four everolimus eluting stents. Initially the patient made an unremarkable recovery until ventricular fibrillation arrest occurred on the following day. Unsynchronized cardioversion restored a normal sinus rhythm and repeat catheterization revealed new right coronary artery (RCA dissection. A wire was passed distally, but it was unclear whether this was through the true or false lumen and no stents could be placed. However, improvement of distal RCA perfusion was noted on angiogram. Despite failure of interventional therapy the patient was therefore treated conservatively. Early operation after myocardial infarction has a significantly elevated risk of mortality and the initial dissection had occurred within 24 hours. This strategy proved successful as follow-up transthoracic echocardiography after four months demonstrated a preserved left ventricular ejection fraction of 55-60% without regional wall motion abnormalities. The patient remained asymptomatic from a cardiac point of view.

  10. Rotational atherectomy before paclitaxel-eluting stent implantation in complex calcified coronary lesions: Two-year clinical outcome of the randomized ROTAXUS trial.

    Science.gov (United States)

    de Waha, Suzanne; Allali, Abdelhakim; Büttner, Heinz-Joachim; Toelg, Ralph; Geist, Volker; Neumann, Franz-Josef; Khattab, Ahmed A; Richardt, Gert; Abdel-Wahab, Mohamed

    2016-03-01

    In the randomized ROTAXUS trial, routine lesion preparation of complex calcified coronary lesions using rotational atherectomy (RA) prior to paclitaxel-eluting stent implantation did not reduce the primary endpoint of angiographic late lumen loss at 9 months compared to stenting without RA. So far, no long-term data of prospective head-to-head comparisons between both treatment strategies have been reported. ROTAXUS randomly assigned patients with complex calcified coronary lesions to RA followed by stenting (n = 120) or stenting without RA (n = 120). The primary endpoint of the current analysis was the occurrence of major adverse cardiac events (MACE) at 2-year follow-up defined as the composite of death, myocardial infarction, and target vessel revascularization (TVR). At 2 years, MACE occurred in 32 patients in the RA group and 37 patients in the standard therapy group (29.4% vs. 34.3%, P = 0.47). The rates of death (8.3% vs. 7.4%, P = 1.00), myocardial infarction (8.3% vs. 6.5%, P = 0.80), target lesion revascularization (TLR, 13.8% vs. 16.7%, P = 0.58), and TVR (19.3% vs. 22.2%, P = 0.62) were similar in both groups. Despite high rates of initial angiographic success, nearly one third of patients enrolled in ROTAXUS experienced MACE within 2-year follow-up, with no differences between patients treated with or without RA. © 2015 Wiley Periodicals, Inc.

  11. Clinical outcome after primary percutaneous coronary intervention with drug-eluting and bare metal stents in patients with ST-segment elevation myocardial infarction

    DEFF Research Database (Denmark)

    Jensen, Lisette Okkels; Maeng, Michael; Thayssen, Per

    2008-01-01

    BACKGROUND: The use of drug-eluting stents (DESs) versus bare metal stents (BMSs) in primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction is a matter of debate. Therefore, we examined the risk of target lesion revascularization (TLR), stent thrombosis...... Registry from January 2002 through June 2005, were followed up for 2 years. We used Cox regression analysis to control for confounding. The 2-year incidence of definite stent thrombosis was 1.9% in the DES group and 1.1% in the BMS group (adjusted relative risk [RR]=1.53; 95% CI=0.84 to 2.78; P=0.17). Very...... late definite stent thrombosis (> or =12 months) was seen in 0.4% in the DES group and 0.06% in the BMS group (adjusted RR=6.74; 95% CI=1.23 to 37.00; P=0.03). The 2-year incidence of myocardial infarction was similar in the 2 groups, 5.2% in the DES group versus 6.3% in the BMS group (P=0.28; adjusted...

  12. Sirolimus-eluting versus bare-metal stent implantation in patients with ostial lesions

    DEFF Research Database (Denmark)

    Jørgensen, Erik; Kelbæk, Henning; Kløvgaard, Lene

    2010-01-01

    To investigate the efficacy of implantation of sirolimus-eluting stents (SES) in the ostium of coronary arteries.......To investigate the efficacy of implantation of sirolimus-eluting stents (SES) in the ostium of coronary arteries....

  13. Very late stent thrombosis with second generation drug eluting stents compared to bare metal stents: Network meta-analysis of randomized primary percutaneous coronary intervention trials.

    Science.gov (United States)

    Philip, Femi; Stewart, Susan; Southard, Jeffrey A

    2016-07-01

    The relative safety of drug-eluting stents (DES) and bare-metal stents (BMS) in primary percutaneous coronary intervention (PPCI) in ST elevation myocardial infarction (STEMI) continues to be debated. The long-term clinical outcomes between second generation DES and BMS for primary percutaneous coronary intervention (PCI) using network meta-analysis were compared. Randomized controlled trials comparing stent types (first generation DES, second generation DES, or BMS) were considered for inclusion. A search strategy used Medline, Embase, Cochrane databases, and proceedings of international meetings. Information about study design, inclusion criteria, and sample characteristics were extracted. Network meta-analysis was used to pool direct (comparison of second generation DES to BMS) and indirect evidence (first generation DES with BMS and second generation DES) from the randomized trials. Twelve trials comparing all stents types including 9,673 patients randomly assigned to treatment groups were analyzed. Second generation DES was associated with significantly lower incidence of definite or probable ST (OR 0.59, 95% CI 0.39-0.89), MI (OR 0.59, 95% CI 0.39-0.89), and TVR at 3 years (OR 0.50: 95% CI 0.31-0.81) compared with BMS. In addition, there was a significantly lower incidence of MACE with second generation DES versus BMS (OR 0.54, 95% CI 0.34-0.74) at 3 years. These were driven by a higher rate of TVR, MI and stent thrombosis in the BMS group at 3 years. There was a non-significant reduction in the overall and cardiac mortality [OR 0.83, 95% CI (0.60-1.14), OR 0.88, 95% CI (0.6-1.28)] with the use of second generation DES versus BMS at 3 years. Network meta-analysis of randomized trials of primary PCI demonstrated lower incidence of MACE, MI, TVR, and stent thrombosis with second generation DES compared with BMS. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  14. Impact of Clinical Presentation (Stable Angina Pectoris vs Unstable Angina Pectoris or Non-ST-Elevation Myocardial Infarction vs ST-Elevation Myocardial Infarction) on Long-Term Outcomes in Women Undergoing Percutaneous Coronary Intervention With Drug-Eluting Stents

    DEFF Research Database (Denmark)

    Giustino, Gennaro; Baber, Usman; Stefanini, Giulio Giuseppe

    2015-01-01

    The long-term risk associated with different coronary artery disease (CAD) presentations in women undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DES) is poorly characterized. We pooled patient-level data for women enrolled in 26 randomized clinical trials. Of 11......,577 women included in the pooled database, 10,133 with known clinical presentation received a DES. Of them, 5,760 (57%) had stable angina pectoris (SAP), 3,594 (35%) had unstable angina pectoris (UAP) or non-ST-segment-elevation myocardial infarction (NSTEMI), and 779 (8%) had ST......-segment-elevation myocardial infarction (STEMI) as clinical presentation. A stepwise increase in 3-year crude cumulative mortality was observed in the transition from SAP to STEMI (4.9% vs 6.1% vs 9.4%; p clinical...

  15. Absence of gender disparity in short-term clinical outcomes in patients with acute ST-segment elevation myocardial infarction undergoing sirolimus-eluting stent based primary coronary intervention: a report from Shanghai Acute Coronary Event (SACE) Registry.

    Science.gov (United States)

    Zhang, Qi; Qiu, Jian-Ping; Zhang, Rui-Yan; Li, Yi-Gang; He, Ben; Jin, Hui-Gen; Zhang, Jun-Feng; Wang, Xiao-Long; Jiang, Li; Liao, Min-Lei; Hu, Jian; Shen, Wei-Feng

    2010-04-05

    Randomized, controlled trials have demonstrated the superiority of sirolimus-eluting stent (SES) implantation during primary percutaneous coronary intervention (PCI), as opposed to bare-metal stents, in patients with ST-elevation myocardial infarction (STEMI). This study aimed to test the hypothesis that clinical benefits of SES treatment were independent of gender in this setting. A total of 2042 patients with STEMI undergoing SES-based primary PCI were prospectively enrolled into Shanghai Acute Coronary Event (SACE) registry (1574 men and 468 women). Baseline demographics, angiographic and PCI features, and in-hospital and 30-day major adverse cardiac events (MACE) were analyzed as a function of gender. Compared with men, women were older and more frequently had hypertension, diabetes, and hypercholesterolemia. Use of platelet glycoprotein IIb/IIIa receptor inhibitor (GPI, 65.5% vs. 62.2%, P = 0.10) and procedural success rate (95.0% vs. 94.2%, P = 0.52) were similar in both genders. In-hospital death and MACE occurred in 3.8% and 7.6%, and 4.5% and 8.1% in the male and female patients, respectively (all P > 0.05). At 30-day follow-up, survival (94.3% vs. 93.8%, P = 0.66) and MACE-free survival (90.2% vs. 89.3%, P = 0.52) did not significantly differ between men and women. After adjustment for differences in patient demographics, angiographic and procedural features, there were no significant difference in either in-hospital (OR = 0.77, 95%CI of 0.48 to 1.22, P = 0.30) or 30-day mortality (OR = 1.28, 95%CI of 0.73 to 2.23, P = 0.38) between women and men. Despite more advanced age and clustering of risk factors in women, female patients with STEMI treated by SES-based primary PCI had similar in-hospital and short-term clinical outcomes as their male counterparts.

  16. Bioresorbable Scaffold for Treatment of Coronary Artery Lesions: Intravascular Ultrasound Results From the ABSORB Japan Trial.

    Science.gov (United States)

    Okada, Kozo; Honda, Yasuhiro; Kitahara, Hideki; Otagiri, Kyuhachi; Tanaka, Shigemitsu; Hollak, M Brooke; Yock, Paul G; Popma, Jeffrey J; Kusano, Hajime; Cheong, Wai-Fung; Sudhir, Krishnankutty; Fitzgerald, Peter J; Kimura, Takeshi

    2018-04-09

    The aim of this study was to characterize post-procedural intravascular ultrasound (IVUS) findings in the ABSORB Japan trial, specifically stratified by the size of target coronary arteries. Despite overall noninferiority confirmed in recent randomized trials comparing bioresorbable vascular scaffolds (BVS) (Absorb BVS) and cobalt-chromium everolimus-eluting metallic stents (CoCr-EES), higher event rates of Absorb BVS have been reported with suboptimal deployment, especially in small coronary arteries. In the ABSORB Japan trial, 150 patients (2:1 randomization) were scheduled in the IVUS cohort. Small vessel was defined as mean reference lumen diameter strategy, possibly different between polymeric and metallic devices, needs to be established for bioresorbable scaffold technology. (AVJ-301 Clinical Trial: A Clinical Evaluation of AVJ-301 Absorb™ BVS) in Japanese Population [ABSORB JAPAN]; NCT01844284). Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  17. Randomized comparison of distal protection versus conventional treatment in primary percutaneous coronary intervention: the drug elution and distal protection in ST-elevation myocardial infarction (DEDICATION) trial

    DEFF Research Database (Denmark)

    Kelbaek, Henning; Terkelsen, Christian J; Helqvist, Steffen

    2008-01-01

    OBJECTIVES: The purpose of this study was to evaluate the use of distal protection during percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) in native coronary vessels. BACKGROUND: Embolization of material from the infarct-related lesion during PCI may...

  18. Left ventricular contractile function after distal protection in primary percutaneous coronary intervention Results from the Drug Elution and Distal Protection in ST-Elevation Myocardial Infarction trial

    DEFF Research Database (Denmark)

    Kofoed, K F; Kelbæk, H; Thuesen, L

    2011-01-01

    Coronary intervention (PCI) may result in an increased infarct size. We evaluated the effect of distal protection during PCI for ST-segment elevation myocardial infarction (STEMI) on myocardial function.......Coronary intervention (PCI) may result in an increased infarct size. We evaluated the effect of distal protection during PCI for ST-segment elevation myocardial infarction (STEMI) on myocardial function....

  19. First-in-man randomised comparison of the BuMA Supreme biodegradable polymer sirolimus-eluting stent versus a durable polymer zotarolimus-eluting coronary stent: the PIONEER trial.

    Science.gov (United States)

    von Birgelen, Clemens; Asano, Taku; Amoroso, Giovanni; Aminian, Adel; Brugaletta, Salvatore; Vrolix, Mathias; Hernandez-Antolín, Rosana; van de Harst, Pim; Iñiguez, Andres; Janssens, Luc; Smits, Pieter C; Wykrzykowska, Joanna J; Ribeiro, Vasco Gama; Pereira, Hélder; da Silva, Pedro Canas; Piek, Jan J; Onuma, Yoshinobu; Serruys, Patrick W; Sabaté, Manel

    2018-04-20

    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 µm) 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. 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 (pnon-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). The PIONEER trial did not meet its primary endpoint in terms of in-stent LLL at nine-month follow-up. However, this result did not translate into any increase in restenosis rate or impairment in 12-month clinical outcomes.

  20. The sirolimus-eluting Cypher Select coronary stent for the treatment of bare-metal and drug-eluting stent restenosis: insights from the e-SELECT (Multicenter Post-Market Surveillance) registry.

    Science.gov (United States)

    Abizaid, Alexandre; Costa, J Ribamar; Banning, Adrian; Bartorelli, Antonio L; Dzavik, Vladimir; Ellis, Stephen; Gao, Runlin; Holmes, David R; Jeong, Muyng Ho; Legrand, Victor; Neumann, Franz-Josef; Nyakern, Maria; Orlick, Amy; Spaulding, Christian; Worthley, Stephen; Urban, Philip M

    2012-01-01

    This study sought to compare the 1-year safety and efficacy of Cypher Select or Cypher Select Plus (Cordis Corporation, Bridgewater, New Jersey) sirolimus-eluting stents (SES) with the treatment of bare-metal stents (BMS) and drug-eluting stent (DES) in-stent restenosis (ISR) in nonselected, real-world patients. There is paucity of consistent data on DES for the treatment of ISR, especially, DES ISR. The e-SELECT (Multicenter Post-Market Surveillance) registry is a Web-based, multicenter and international registry encompassing virtually all subsets of patients and lesions treated with at least 1 SES during the period from 2006 to 2008. We enrolled in this pre-specified subanalysis all patients with at least 1 clinically relevant BMS or DES ISR treated with SES. Primary endpoint was major adverse cardiac events and stent thrombosis rate at 1 year. Of 15,147 patients enrolled, 1,590 (10.5%) presented at least 1 ISR (BMS group, n = 1,235, DES group, n = 355). Patients with DES ISR had higher incidence of diabetes (39.4% vs. 26.9%, p target lesion revascularization and definite/probable late stent thrombosis were higher in patients with DES ISR (6.9% vs. 3.1%, p = 0.003, and 1.8% vs. 0.5%, p = 0.04, respectively). Use of SES for either BMS or DES ISR treatment is safe and associated with low target lesion revascularization recurrence and no apparent safety concern. Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  1. Comparison between the STENTYS self-apposing bare metal and paclitaxel-eluting coronary stents for the treatment of saphenous vein grafts (ADEPT trial)

    NARCIS (Netherlands)

    A.J.J. IJsselmuiden (Alexander); C. Simsek (Cihan); Van Driel, A.G. (A. G.); Bouchez, D. (D.); G. Amoroso (Giovanni); P. Vermeersch (Paul); Karjalainen, P.P. (P. P.)

    2018-01-01

    textabstractAims To describe the safety and performance of STENTYS self-expandable bare metal stents (BMS) versus paclitaxel-eluting stents (PES) in saphenous vein grafts (SVGs). Methods and Results A randomised controlled trial was performed in four hospitals in three European countries between

  2. Neointimal Healing Evaluated by Optical Coherence Tomography after Drug-Eluting Absorbable Metal Scaffold Implantation in de novo Native Coronary Lesions: Rationale and Design of the Magmaris-OCT Study.

    Science.gov (United States)

    Karjalainen, Pasi; Paana, Tuomas; Sia, Jussi; Nammas, Wail

    We sought to explore neointimal healing assessed by optical coherence tomography (OCT) following implantation of the Magmaris sirolimus-eluting absorbable metal scaffold. The Magmaris-OCT is a prospective, multicenter, single-arm observational clinical study, intended to enrol 60 consecutive patients with up to 2 de novo native coronary lesions, each located in different major epicardial vessels, with a reference vessel diameter of 2.5-3.5 mm, and a maximum lesion length of 20 mm. Patients will undergo Magmaris scaffold implantation in the target lesion, according to the standard practice. Clinical follow-up will take place at 30 days, and at 3, 6, 9, and 12 months. For invasive-imaging follow-up, patients will be classified into 3 groups: cohort A will be scheduled for follow-up at 3 months, cohort B at 6 months, and cohort C at 12 months. Invasive imaging will include quantitative coronary angiography, OCT evaluation, and coronary flow reserve measurement. The primary end point will be the percentage of uncovered scaffold struts assessed by OCT at the prespecified follow-up. This study will provide insight into the short- and mid-term healing properties following Magmaris scaffold implantation, with special emphasis on the neointimal coverage of scaffold struts. © 2017 S. Karger AG, Basel.

  3. Improved safety and reduction in stent thrombosis associated with biodegradable polymer-based biolimus-eluting stents versus durable polymer-based sirolimus-eluting stents in patients with coronary artery disease: final 5-year report of the LEADERS (Limus Eluted From A Durable Versus ERodable Stent Coating) randomized, noninferiority trial.

    Science.gov (United States)

    Serruys, Patrick W; Farooq, Vasim; Kalesan, Bindu; de Vries, Ton; Buszman, Pawel; Linke, Axel; Ischinger, Thomas; Klauss, Volker; Eberli, Franz; Wijns, William; Morice, Marie Claude; Di Mario, Carlo; Corti, Roberto; Antoni, Diethmar; Sohn, Hae Y; Eerdmans, Pedro; Rademaker-Havinga, Tessa; van Es, Gerrit-Anne; Meier, Bernhard; Jüni, Peter; Windecker, Stephan

    2013-08-01

    This study sought to report the final 5 years follow-up of the landmark LEADERS (Limus Eluted From A Durable Versus ERodable Stent Coating) trial. The LEADERS trial is the first randomized study to evaluate biodegradable polymer-based drug-eluting stents (DES) against durable polymer DES. The LEADERS trial was a 10-center, assessor-blind, noninferiority, "all-comers" trial (N = 1,707). All patients were centrally randomized to treatment with either biodegradable polymer biolimus-eluting stents (BES) (n = 857) or durable polymer sirolimus-eluting stents (SES) (n = 850). The primary endpoint was a composite of cardiac death, myocardial infarction (MI), or clinically indicated target vessel revascularization within 9 months. Secondary endpoints included extending the primary endpoint to 5 years and stent thrombosis (ST) (Academic Research Consortium definition). Analysis was by intention to treat. At 5 years, the BES was noninferior to SES for the primary endpoint (186 [22.3%] vs. 216 [26.1%], rate ratio [RR]: 0.83 [95% confidence interval (CI): 0.68 to 1.02], p for noninferiority 1 year) and associated composite clinical outcomes. (Limus Eluted From A Durable Versus ERodable Stent Coating [LEADERS] trial; NCT00389220). Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  4. Social inhibition modulates the effect of negative emotions on cardiac prognosis following percutaneous coronary intervention in the drug-eluting stent era

    DEFF Research Database (Denmark)

    Denollet, Johan; Pedersen, Susanne S.; Ong, Andrew T L

    2006-01-01

    Negative emotions have an adverse effect on cardiac prognosis. We investigated whether social inhibition (inhibited self-expression in social interaction) modulates the effect of negative emotions on clinical outcome following percutaneous coronary intervention (PCI).......Negative emotions have an adverse effect on cardiac prognosis. We investigated whether social inhibition (inhibited self-expression in social interaction) modulates the effect of negative emotions on clinical outcome following percutaneous coronary intervention (PCI)....

  5. Drug eluting stents trapping intramural hematoma in spontaneous coronary artery dissection and healing pattern at six months: Optical coherence tomography findings

    Energy Technology Data Exchange (ETDEWEB)

    Poon, Karl, E-mail: karlkpoon@gmail.com; Incani, Alexander; Small, Andrew; Raffel, O. Christopher

    2013-05-15

    Spontaneous coronary artery dissections (SCAD) are often difficult to diagnose and manage. Intravascular imaging such as optical coherence tomography (OCT) improves diagnosis and may assist in management. Recent data suggest that percutaneous coronary interventions (PCI) in in SCAD are associated with poor outcomes. This report provides striking OCT images of potential complications associated with PCI in SCAD, as well as demonstrates medium term OCT data in residual hematoma healing and stent coverage in SCAD.

  6. Meta-analysis comparing efficacy and safety of first generation drug-eluting stents to bare-metal stents in patients with diabetes mellitus undergoing primary percutaneous coronary intervention

    DEFF Research Database (Denmark)

    De Luca, Giuseppe; Dirksen, Maurits T; Spaulding, Christian

    2013-01-01

    revascularization (hazard ratio 0.42, 95% confidence interval 0.29 to 0.59, p 1 year) with DES. In conclusion, this meta-analysis, based on individual patients' data from 11 randomized trials, showed that among patients with diabetes with STEMIs who undergo primary percutaneous coronary intervention, sirolimus...... with high rates of target vessel revascularization after bare-metal stent (BMS) implantation but also higher rates of ST after DES implantation. Therefore, the aim of this study was to perform a meta-analysis of individual patients' data to evaluate the long-term safety and effectiveness of DES compared......Several concerns have emerged regarding the higher risk for stent thrombosis (ST) after drug-eluting stent (DES) implantation, especially in the setting of ST-segment elevation myocardial infarction (STEMI). Few data have been reported so far in patients with diabetes mellitus, which is associated...

  7. Propensity score matched lesion-based comparison of long-term clinical and angiographic outcomes after placement of sirolimus (Cypher Bx Velocity) and paclitaxel (TAXUS Express)-eluting stents for de novo native coronary stenosis.

    Science.gov (United States)

    Nakano, Yosuke; Ishikawa, Tetsuya; Hino, Shoryoku; Mutoh, Makoto

    2014-04-01

    Long-term clinical and angiographic outcomes after sirolimus (SES: Cypher Bx Velocity) and paclitaxel (PES: TAXUS Express)-eluting stent implantation were firstly compared in Japan. During PES-available period from May 2007 to February 2009, 1068 nonrandomized consecutive de novo native coronary lesions treated either with a PES (682 lesions) or SES were enrolled in this study, and a retrospective examination was conducted in April 2013. During that interval, the use ratio of drug-eluting stent (i.e. SES plus PES) was 94.2 %. By adjusting the baselines with a propensity score matching analysis produced 383 lesions in each arm, the incidence of the clinical endpoint (1500-day cardiac death, nonfatal recurrent myocardial infarction, and definite stent thrombosis) after placement of SES (2.1 %; mean follow-up, 1400 ± 290 days) was not significantly different from that in the PES group (2.6 %; 1394 ± 325 days, p = 0.637). SES did not relate to the clinical endpoint (hazard ratio 1.04; 95 % CI 0.29-3.76; p = 0.949). In the baseline-adjusted angiographic followed up lesions (n = 234 in each arm), the incidence of binary restenosis (percent diameter stenosis [%DS] >50 %) in the SES group (12.0 %; mean follow-up, 477 ± 281 days) was not significantly different from that in the PES group (14.5 %; 497 ± 341 days, p = 0.431). SES did not relate to binary restenosis (Odds ratio 0.73; 95 % CI 0.40-1.32; p = 0.295). In conclusion, the present propensity score matched lesion-based analysis firstly showed the statistical equivalent long-term clinical and angiographic outcomes after either SES or PES placement for de novo native coronary lesion in Japanese patients in a daily practice environment.

  8. Red blood cell distribution width and long-term outcome in patients undergoing percutaneous coronary intervention in the drug-eluting stenting era: a two-year cohort study.

    Science.gov (United States)

    Yao, Hai-Mu; Sun, Tong-Wen; Zhang, Xiao-Juan; Shen, De-Liang; Du, You-You; Wan, You-Dong; Zhang, Jin-Ying; Li, Ling; Zhao, Luo-Sha

    2014-01-01

    Previous studies suggest the higher the red blood cell distribution width (RDW) the greater the risk of mortality in patients with coronary artery disease (CAD). However, the relationship between RDW and long-term outcome in CAD patients undergoing percutaneous coronary intervention (PCI) with a drug-eluting stent (DES) remains unclear. This study was designed to evaluate the long-term effect of RDW in patients treated with drug-eluting stent for CAD. In total of 2169 non-anemic patients (1468 men, mean age 60.2 ± 10.9 years) with CAD who had undergone successful PCI and had at least one drug-eluting stent were included in this study. Patients were grouped according to their baseline RDW: Quartile 1 (RDW<12.27%), Quartile 2 (12.27% ≤ RDW <13%), Quartile 3 (13% ≤ RDW<13.5%), and Quartile 4 (RDW ≥ 13.5). The incidence of in-hospital mortality and death or myocardial infarction was significantly higher in Quartiles 3 and 4 compared with Quartile 1 (P<0.05). After a follow-up of 29 months, the incidence of all-cause death and stent thrombosis in Quartile 4 was higher than in Quartiles 1, 2, and 3 (P<0.05). The incidence of death/myocardial infarction/stroke and cardiac death in Quartile 4 was higher than in Quartiles 1 and 2 (P<0.05). Multivariate Cox regression analysis showed that RDW was an independent predictor of all-cause death (hazard ratio (HR) = 1.37, 95% confidence interval (CI) = 1.15-1.62, P<0.001) and outcomes of death/myocardial infarction/stroke (HR = 1.21, 95% CI = 1.04-1.39, P = 0.013). The cumulative survival rate of Quartile 4 was lower than that of Quartiles 1, 2, and 3 (P<0.05). High RDW is an independent predictor of long-term adverse clinical outcomes in non-anemic patients with CAD treated with DES.

  9. Red blood cell distribution width and long-term outcome in patients undergoing percutaneous coronary intervention in the drug-eluting stenting era: a two-year cohort study.

    Directory of Open Access Journals (Sweden)

    Hai-Mu Yao

    Full Text Available BACKGROUND: Previous studies suggest the higher the red blood cell distribution width (RDW the greater the risk of mortality in patients with coronary artery disease (CAD. However, the relationship between RDW and long-term outcome in CAD patients undergoing percutaneous coronary intervention (PCI with a drug-eluting stent (DES remains unclear. This study was designed to evaluate the long-term effect of RDW in patients treated with drug-eluting stent for CAD. METHODS: In total of 2169 non-anemic patients (1468 men, mean age 60.2 ± 10.9 years with CAD who had undergone successful PCI and had at least one drug-eluting stent were included in this study. Patients were grouped according to their baseline RDW: Quartile 1 (RDW<12.27%, Quartile 2 (12.27% ≤ RDW <13%, Quartile 3 (13% ≤ RDW<13.5%, and Quartile 4 (RDW ≥ 13.5. RESULTS: The incidence of in-hospital mortality and death or myocardial infarction was significantly higher in Quartiles 3 and 4 compared with Quartile 1 (P<0.05. After a follow-up of 29 months, the incidence of all-cause death and stent thrombosis in Quartile 4 was higher than in Quartiles 1, 2, and 3 (P<0.05. The incidence of death/myocardial infarction/stroke and cardiac death in Quartile 4 was higher than in Quartiles 1 and 2 (P<0.05. Multivariate Cox regression analysis showed that RDW was an independent predictor of all-cause death (hazard ratio (HR = 1.37, 95% confidence interval (CI = 1.15-1.62, P<0.001 and outcomes of death/myocardial infarction/stroke (HR = 1.21, 95% CI = 1.04-1.39, P = 0.013. The cumulative survival rate of Quartile 4 was lower than that of Quartiles 1, 2, and 3 (P<0.05. CONCLUSION: High RDW is an independent predictor of long-term adverse clinical outcomes in non-anemic patients with CAD treated with DES.

  10. Impact of Clinical Presentation (Stable Angina Pectoris vs Unstable Angina Pectoris or Non-ST-Elevation Myocardial Infarction vs ST-Elevation Myocardial Infarction) on Long-Term Outcomes in Women Undergoing Percutaneous Coronary Intervention With Drug-Eluting Stents.

    Science.gov (United States)

    Giustino, Gennaro; Baber, Usman; Stefanini, Giulio Giuseppe; Aquino, Melissa; Stone, Gregg W; Sartori, Samantha; Steg, Philippe Gabriel; Wijns, William; Smits, Pieter C; Jeger, Raban V; Leon, Martin B; Windecker, Stephan; Serruys, Patrick W; Morice, Marie-Claude; Camenzind, Edoardo; Weisz, Giora; Kandzari, David; Dangas, George D; Mastoris, Ioannis; Von Birgelen, Clemens; Galatius, Soren; Kimura, Takeshi; Mikhail, Ghada; Itchhaporia, Dipti; Mehta, Laxmi; Ortega, Rebecca; Kim, Hyo-Soo; Valgimigli, Marco; Kastrati, Adnan; Chieffo, Alaide; Mehran, Roxana

    2015-09-15

    The long-term risk associated with different coronary artery disease (CAD) presentations in women undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DES) is poorly characterized. We pooled patient-level data for women enrolled in 26 randomized clinical trials. Of 11,577 women included in the pooled database, 10,133 with known clinical presentation received a DES. Of them, 5,760 (57%) had stable angina pectoris (SAP), 3,594 (35%) had unstable angina pectoris (UAP) or non-ST-segment-elevation myocardial infarction (NSTEMI), and 779 (8%) had ST-segment-elevation myocardial infarction (STEMI) as clinical presentation. A stepwise increase in 3-year crude cumulative mortality was observed in the transition from SAP to STEMI (4.9% vs 6.1% vs 9.4%; p clinical presentations. After multivariable adjustment, STEMI was independently associated with greater risk of 3-year mortality (hazard ratio [HR] 3.45; 95% confidence interval [CI] 1.99 to 5.98; p clinical spectrum of CAD, STEMI was associated with a greater risk of long-term mortality. Conversely, the adjusted risk of mortality between UAP or NSTEMI and SAP was similar. New-generation DESs provide improved long-term clinical outcomes irrespective of the clinical presentation in women. Published by Elsevier Inc.

  11. Angiographic patterns of in-stent restenosis classified by computed tomography in patients with drug-eluting stents: correlation with invasive coronary angiography

    International Nuclear Information System (INIS)

    Pan, Jingwei; Lu, Zhigang; Wei, Meng; Zhang, Jiayin; Li, Minghua

    2013-01-01

    To evaluate the diagnostic accuracy of Mehran's in-stent restenosis (ISR) classification by coronary computed angiography (CCTA), with reference to invasive coronary angiography (ICA). Consecutive symptomatic patients, who had clinically suspected ISR and implanted stent diameter ≥ 3 mm, were prospectively enrolled in our study. Mehran's classification was employed by CCTA and ICA to classify ISR lesions into four subtypes: focal, diffuse intrastent, diffuse proliferative and total occlusion. CCTA and ICA measurement of lesion length was further compared. Sixty-one patients with 101 implanted stents were included in our study. The overall sensitivity, specificity, PPV and NPV of CCTA diagnosis of binary ISR, as shown by patient-based analysis (n = 61), were 100 % (49/49), 75 % (8/12), 92.45 % (49/53) and 100 % (8/8) respectively. Mehran's classification of CCTA correlated well with ICA findings. The diagnostic accuracy of CCTA for class I, class II, class III and class IV lesions was 92.5 %, 91.67 %, 100 % and 100 % respectively. Lesion length was assessed to be significantly longer with CCTA than with ICA (11.03 ± 5.89 mm versus 8.56 ± 4.99 mm, P < 0.001). Angiographic patterns of in-stent restenosis can be accurately classified by coronary computed angiography. The lesion length measured by CCTA is longer than that assessed by invasive coronary angiography. (orig.)

  12. Everolimus in Heart Transplantation: An Update

    Directory of Open Access Journals (Sweden)

    Stephan W. Hirt

    2013-01-01

    Full Text Available The evidence base relating to the use of everolimus in heart transplantation has expanded considerably in recent years, providing clinically relevant information regarding its use in clinical practice. Unless there are special considerations to take into account, all de novo heart transplant patients can be regarded as potential candidates for immunosuppression with everolimus and reduced-exposure calcineurin inhibitor therapy. Caution about the use of everolimus immediately after transplantation should be exercised in certain patients with the risk of severe proteinuria, with poor wound healing, or with uncontrolled severe hyperlipidemia. Initiation of everolimus in the early phase aftertransplant is not advisable in patients with severe pretransplant end-organ dysfunction or in patients on a left ventricular assist device beforetransplant who are at high risk of infection or of wound healing complications. The most frequent reason for introducing everolimus in maintenance heart transplant patients is to support minimization or withdrawal of calcineurin inhibitor therapy, for example, due to impaired renal function or malignancy. Due to its potential to inhibit the progression of cardiac allograft vasculopathy and to reduce cytomegalovirus infection, everolimus should be initiated as soon as possible after heart transplantation. Immediate and adequate reduction of CNI exposure is mandatory from the start of everolimus therapy.

  13. Effect of cytochrome P450 2C19 polymorphism on adverse cardiovascular events after drug-eluting stent implantation in a large Hakka population with acute coronary syndrome receiving clopidogrel in southern China.

    Science.gov (United States)

    Zhong, Zhixiong; Hou, Jingyuan; Zhang, Qifeng; Li, Bin; Li, Cunren; Liu, Zhidong; Yang, Min; Zhong, Wei; He, Xuebo; Wu, Hesen; Zhong, Miaocai; Zhao, Pingsen

    2018-04-01

    The objective of this study is to evaluate the effects of cytochrome P450 2C19 (CYP2C19) polymorphism on adverse cardiovascular events (MACE) in Hakka patients with acute coronary syndrome (ACS) receiving clopidogrel who had undergone coronary drug-eluting stent placement after percutaneous coronary intervention (PCI) in southern China. Genotyping of CYP2C19 and MACE of 934 ACS patients with PCI on clopidogrel maintenance therapy were analyzed. Patients who carried loss-of-function CYP2C19 were treated with a 150-mg maintenance dose of clopidogrel or 90 mg of ticagrelor antiplatelet therapy, and patients who were non-carriers received clopidogrel therapy daily at a maintenance dose of 75 mg and the patients were followed-up for at least 12 months. The primary efficacy endpoint was a composite of cardiovascular death, myocardial infarction, and target vessel revascularization and stroke. The allelic frequency of CYP2C19*2 and CYP2C19*3 of Hakka patients in the current study was 31.64 and 5.19%, respectively. The CYP2C19 wild-type homozygotes (*1/*1) were the most predominant among the patients (40.36%), followed by the CYP2C19*2 heterozygotes (*1/*2) (40.26%). The distribution of CYP2C19 phenotypes was divided into extensive metabolizers (EM; 40.36%), intermediate metabolizers (IM; 45.61%), and poor metabolizers (PM; 14.03%). Based on the genotype-guided antiplatelet therapy, there was no significant association between the carrier status and the clinical outcome at 1, 6, and 12 months. In addition, no significant difference in the rates of bleeding was found among the three groups. After logistic regression analysis, hypertension was the only independent predictor of cardiovascular events (relative risk, 1.501; 95% CI, 1.011 to 2.229; P = 0.044). Our results shed new light on the important benefit of testing CYP2C19 polymorphisms before prescribing clopidogrel in patients treated with drug-eluting stent implantation after PCI. The testing may help to

  14. Long-term outcome in patients treated with sirolimus-eluting stents in complex coronary artery lesions: 3-year results of the SCANDSTENT (Stenting Coronary Arteries in Non-Stress/Benestent Disease) trial

    DEFF Research Database (Denmark)

    Kelbaek, H.; Klovgaard, L.; Helqvist, S.

    2008-01-01

    data of the long-term outcome of patients with complex coronary artery lesions. METHODS: We randomly assigned 322 patients with total coronary occlusions or lesions located in bifurcations, ostial, or angulated segments of the coronary arteries to have SES or BMS implanted. RESULTS: At 3 years, major...... performed between 1 and 3 years after the index treatment (p = NS). According to revised definitions, stent thrombosis occurred in 5 patients (3.1%) in the SES group and in 7 patients (4.4%) in the BMS group (p = NS); very late stent thrombosis was observed in 4 versus 1 patient. CONCLUSIONS: A continued...

  15. Long-term clinical and angiographic results of Sirolimus-Eluting Stent in Complex Coronary Chronic Total Occlusion Revascularization: the SECTOR registry.

    Science.gov (United States)

    Galassi, Alfredo R; Tomasello, Salvatore D; Costanzo, Luca; Campisano, Maria B; Barrano, Giombattista; Tamburino, Corrado

    2011-10-01

    Drug-eluting stents showed a better angiographic and clinical outcome in comparison with bare metal stent in chronic total occlusions (CTOs) percutaneous revascularization, however, great concerns still remain regarding the rate of restenosis and reocclusion in comparison with nonocclusive lesions. To evaluate angiographic and clinical outcomes after sirolimus-eluting stent (SES) implantation in the setting of a "real world" series of complex CTOs. From January 2006 to December 2008, 172 consecutive patients with 179 CTO lesions were enrolled into registry. Among these, successful recanalization was obtained in 144 lesions (80.4%) with exclusive SES implantation in 104 lesions. The 9-12 months angiographic follow-up was executed in 85.5% of lesions with evidence of angiographic binary restenosis in 16.8% of lesions. Total stent length and number of stent implanted were recognized as independent predictors of restenosis (odds ratio [OR] 4.7, 95% confidence interval [CI] 1.28-107.09, P = 0.02) and (OR 5.8, 95% CI 1.39-23.55, P = 0.01), respectively.The 2-year clinical follow-up showed rates of target lesion revascularization, non-Q wave myocardial infarction, and total major adverse cardiovascular events (MACEs) of 11.1%, 2%, and 13.1%, respectively. Cox proportional-hazard analysis showed diabetes as independent predictor of MACEs (hazard ratio [HR] 4.832; 95% CI, 0.730-0.861; P = 0.028). Data from this registry demonstrate the long-term efficacy and safety of SES implantation after complex CTOs recanalization. ©2011, Wiley Periodicals, Inc.

  16. Revascularization for Left Main and Multivessel Coronary Artery Disease: Current Status and Future Prospects after the EXCEL and NOBLE Trials.

    Science.gov (United States)

    Al-Hijji, Mohammed; El Sabbagh, Abdallah; Holmes, David R

    2018-06-01

    Revascularization of severe left main and multivessel coronary artery disease has been shown to improve survival in both stable ischemic heart disease and acute coronary syndrome. While revascularization with coronary artery bypass surgery for these disease entities carries class I recommendation in most current guidelines, recent trials has shown potential comparable survival and cardiovascular outcomes between percutaneous and surgical interventions in patients with less complex coronary anatomy. Despite the conflicting results observed in the most recent left main revascularization trials, Everolimus-Eluting Stents or Bypass Surgery for Left Main Coronary Artery Disease (EXCEL) and Nordic-Baltic-British left main revascularization (NOBLE), both treatment strategies remain important for the management of left main disease (LMD) and multivessel disease (MVD) reflecting on the importance of heart team discussion. This review is focused on revascularization of LMD and MVD in patients who are not presenting with ST-segment elevation myocardial infarction, encompassing the evidence from historic and contemporary trials which shaped up current practices. This review discusses the heart team approach to guide decision making, including special populations that are not represented in clinical trials. Copyright © 2018. The Korean Society of Cardiology.

  17. Adjuvant Everolimus for Resected Kidney Cancer

    Science.gov (United States)

    In this clinical trial, patients with renal cell cancer who have undergone partial or complete nephrectomy will be randomly assigned to take everolimus tablets or matching placebo tablets daily for 54 weeks.

  18. Long-Term Safety of Drug-Eluting and Bare-Metal Stents

    DEFF Research Database (Denmark)

    Palmerini, Tullio; Benedetto, Umberto; Biondi-Zoccai, Giuseppe

    2015-01-01

    BACKGROUND: Previous meta-analyses have investigated the relative safety and efficacy profiles of different types of drug-eluting stents (DES) and bare-metal stents (BMS); however, most prior trials in these meta-analyses reported follow-up to only 1 year, and as such, the relative long-term safety....... RESULTS: Fifty-one trials that included a total of 52,158 randomized patients with follow-up duration ≥3 years were analyzed. At a median follow-up of 3.8 years, cobalt-chromium everolimus-eluting stents (EES) were associated with lower rates of mortality, definite stent thrombosis (ST), and myocardial...... infarction than BMS, paclitaxel-eluting stents (PES), and sirolimus-eluting stents (SES) and less ST than BES. Phosphorylcholine-based zotarolimus-eluting stents had lower rates of definite ST than SES and lower rates of myocardial infarction than BMS and PES. The late rates of target...

  19. Fatal acute pulmonary injury associated with everolimus.

    Science.gov (United States)

    Depuydt, Pieter; Nollet, Joke; Benoit, Dominique; Praet, Marleen; Caes, Frank

    2012-03-01

    To report a case of fatal alveolar hemorrhage associated with the use of everolimus in a patient who underwent a solid organ transplant. In a 71-year-old cardiac transplant patient, cyclosporine was replaced with everolimus because of worsening renal function. Over the following weeks, the patient developed nonproductive cough and increasing dyspnea. His condition deteriorated to acute respiratory failure with hemoptysis, requiring hospital admission. Bilateral patchy alveolar infiltrates were apparent on chest X-ray and computed tomography. Cardiac failure was ruled out and empiric antimicrobial therapy was initiated. Additional extensive workup could not document opportunistic infection. Everolimus was discontinued and high-dose corticosteroid therapy was initiated. Despite this, the patient required invasive mechanical ventilation and died because of refractory massive hemoptysis. Autopsy revealed diffuse alveolar hemorrhage. Everolimus is a mammalian target of rapamycin inhibitor approved for use as an immunosuppressant and antineoplastic agent. Its main advantage over calcineurin inhibitors (tacrolimus and cyclosporine) is a distinct safety profile. Although it has become clear that everolimus induces pulmonary toxicity more frequently than initially thought, most published cases thus far represented mild and reversible disease, and none was fatal. Here, we report a case of pulmonary toxicity developing over weeks following the introduction of everolimus, in which a fatal outcome could not be prevented by drug withdrawal and corticosteroid treatment. The association of everolimus and this syndrome was probable according to the Naranjo probability scale. This case indicates that with the increasing use of everolimus, clinicians should be aware of the rare, but life-threatening manifestation of pulmonary toxicity.

  20. Determining clinical benefits of drug-eluting coronary stents according to the population risk profile: a meta-regression from 31 randomized trials.

    Science.gov (United States)

    Moreno, Raul; Martin-Reyes, Roberto; Jimenez-Valero, Santiago; Sanchez-Recalde, Angel; Galeote, Guillermo; Calvo, Luis; Plaza, Ignacio; Lopez-Sendon, Jose-Luis

    2011-04-01

    The use of drug-eluting stents (DES) in unfavourable patients has been associated with higher rates of clinical complications and stent thrombosis, and because of that concerns about the use of DES in high-risk settings have been raised. This study sought to demonstrate that the clinical benefit of DES increases as the risk profile of the patients increases. A meta-regression analysis from 31 randomized trials that compared DES and bare-metal stents, including overall 12,035 patients, was performed. The relationship between the clinical benefit of using DES (number of patients to treat [NNT] to prevent one episode of target lesion revascularization [TLR]), and the risk profile of the population (rate of TLR in patients allocated to bare-metal stents) in each trial was evaluated. The clinical benefit of DES increased as the risk profile of each study population increased: NNT for TLR=31.1-1.2 (TLR for bare-metal stents); prisk profile of each study population, since the effect of DES in mortality, myocardial infarction, and stent thrombosis, was not adversely affected by the risk profile of each study population (95% confidence interval for β value 0.09 to 0.11, -0.12 to 0.19, and -0.03 to-0.15 for mortality, myocardial infarction, and stent thrombosis, respectively). The clinical benefit of DES increases as the risk profile of the patients increases, without affecting safety. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.

  1. [Comparison of DK crush with classical crush technique with drug-eluting stents for the treatment of coronary bifurcation lesions from DKCRUSH-1 study].

    Science.gov (United States)

    Chen, Shao-liang; Zhang, Jun-jie; Ye, Fei; Chen, Yun-dai; Lü, Shu-zheng; Tan, Huaycheem; Patel, Tejas; Kenji, Kawajiri; Tamari, Israel; Shan, Shou-jie; Zhu, Zhong-sheng; Lin, Song; Tian, Nai-liang; Li, Xiao-bo; Liu, Zhi-zhong; Lee, Michael; Wei, Meng; Xu, Ya-wei; Yuan, Zheng-bai; Qian, Jun; Sun, Xue-wen; Yang, Song; Chen, Jin-guo; He, Ben; Sumit, Suji

    2008-02-01

    To determine independent factors correlated with clinical effects of DK crush and classical crush technique with drug-eluting stents on bifurcation lesions. 311 patients with bifurcation lesions were randomized to classical (C, n = 156) or double kissing (DK) crush (n = 155) stent implantation group. The primary endpoints included major adverse cardiac events (MACE). Final kissing balloon inflation (FKBI) success rate was 76% in C and 100% in DK groups (P DK crush procedure was characterized by lower unsatisfactory FKBI rate (27.6% vs.6.3%, P DK groups (P = 0.01), respectively. Cumulative 8-month MACE was 35.9% in without-FKBI and 19.7% in with-FKBI sub-groups, and 11.4% in DK group (P = 0.02). The incidence of stent thrombosis was 3.2% in C group (5.1% without vs. 1.7% with FKBI) and 1.3% in DK group (P > 0.05). The predictive factors of MACE included minimal side branch stent lumen diameter and lack of DK crush technique. DK crush technique is an alternative of double stenting techniques in terms of improvement of restenosis and clinical outcomes.

  2. From drug eluting stents to bioresorbable scaffolds; to new horizons in PCI

    NARCIS (Netherlands)

    Tenekecioglu, Erhan; Bourantas, Christos; Abdelghani, Mohammad; Zeng, Yaping; Silva, Rafael Cavalcante; Tateishi, Hiroki; Sotomi, Yohei; Onuma, Yoshinobu; Yılmaz, Mustafa; Serruys, Patrick W.

    2016-01-01

    Drug eluting stents and particularly the fully bioresorbable drug-eluting scaffolds herald a new era in percutaneous treatment of coronary artery disease. There has been tremendous progress in drug eluting stents with fully biodegradable coating polymers and polymer-free devices with reservoir

  3. Differential Clinical Outcomes Between Angiographic Complete Versus Incomplete Coronary Revascularization, According to the Presence of Chronic Kidney Disease in the Drug-Eluting Stent Era.

    Science.gov (United States)

    Kim, Jihoon; Lee, Joo Myung; Choi, Ki Hong; Rhee, Tae-Min; Hwang, Doyeon; Park, Jonghanne; Ahn, Chul; Park, Taek Kyu; Yang, Jeong Hoon; Song, Young Bin; Choi, Jin-Ho; Hahn, Joo-Yong; Choi, Seung-Hyuk; Gwon, Hyeon-Cheol

    2018-02-15

    There are limited data regarding the prognostic impact of angiographic complete revascularization (CR) in patients with chronic kidney disease (CKD). We sought to investigate the differential prognostic impact of angiographic CR over incomplete revascularization (IR), according to the presence of CKD in the drug-eluting stent era. Between 2003 and 2011 at Samsung Medical Center, consecutive patients with multivessel disease were stratified by the presence of CKD (estimated glomerular filtration rate <60 mL/min per 1.73 m 2 ) and classified according to angiographic CR (residual SYNTAX score=0) or IR. Clinical outcomes were compared between angiographic CR and IR, stratified by the presence of CKD. Primary outcome was patient-oriented composite outcomes (POCO, a composite of all-cause death, myocardial infarction, any revascularization) at 3 years. Inverse probability weighting was performed between the CR and IR groups. A total of 3224 patients were eligible for analysis: 2295 without CKD; 929 with CKD. Among non-CKD patients, angiographic CR showed a significantly lower risk of POCO than IR (17.2% versus 21.7%, adjusted hazard ratio 0.76, 95% confidence interval, 0.62-0.95, P =0.014), mainly driven by a significantly lower risk of any revascularization. Among CKD patients, however, angiographic CR was associated with a significantly higher risk of POCO than IR (37.7% versus 28.4%, adjusted hazard ratio 1.42, 95% confidence interval, 1.08%-1.85%, P =0.011), mainly driven by a significantly higher risk of nonfatal target vessel myocardial infarction. Angiographic CR was associated with reduced risk of POCO than IR in patients without CKD; however, it was associated with a significantly higher risk of POCO and nonfatal myocardial infarction in CKD patients. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  4. Study comparing the double kissing (DK) crush with classical crush for the treatment of coronary bifurcation lesions: the DKCRUSH-1 Bifurcation Study with drug-eluting stents.

    Science.gov (United States)

    Chen, S L; Zhang, J J; Ye, F; Chen, Y D; Patel, T; Kawajiri, K; Lee, M; Kwan, T W; Mintz, G; Tan, H C

    2008-06-01

    Classical crush has a lower rate of final kissing balloon inflation (FKBI) immediately after percutaneous coronary intervention (PCI). The double kissing (DK) crush technique has the potential to increase the FKBI rate, and no prospective studies on the comparison of classical with DK crush techniques have been reported. Three hundred and eleven patients with true bifurcation lesions were randomly divided into classical (n = 156) and DK crush (n = 155) groups. Clinical and angiographic details at follow-up at 8 months were indexed. The primary end point was major adverse cardiac events (MACE) including myocardial infarction, cardiac death and target lesion revascularization (TLR) at 8 months. FKBI was 76% in the classical crush group and 100% in the DK group (P DK crush group. Cumulative 8 month MACE was 24.4% in the classical crush group and 11.4% in the DK crush group (P = 0.02). The TLR-free survival rate was 75.4% in the classical crush group and 89.5% in the DK crush group (P = 0.002). DK crush technique has the potential of increasing FKBI rate and reducing stent thrombosis, with a further reduction of TLR and cumulative MACE rate at 8 months.

  5. Drug-eluting stents and bare metal stents in patients with NSTE-ACS

    DEFF Research Database (Denmark)

    Pedersen, Sune Haahr; Pfisterer, Matthias; Kaiser, Christoph

    2014-01-01

    the randomised BASKET-PROVE trial (sirolimus-eluting stent vs. everolimus-eluting stent vs. bare metal stent in large-vessel stenting). The primary endpoint was the combined two-year rate of cardiovascular death or non-fatal myocardial infarction (MI). Secondary endpoints were each component of the primary...... implantation in large vessels was associated with a reduction in both TVR and the combined endpoint consisting of cardiovascular death/MI. Thus, DES use improves both efficacy and safety. These findings support the use of DES in NSTE-ACS patients....

  6. Stent thrombosis and bleeding complications after implantation of sirolimus-eluting coronary stents in an unselected worldwide population: a report from the e-SELECT (Multi-Center Post-Market Surveillance) registry.

    Science.gov (United States)

    Urban, Philip; Abizaid, Alexandre; Banning, Adrian; Bartorelli, Antonio L; Baux, Ana Cebrian; Džavík, Vladimír; Ellis, Stephen; Gao, Runlin; Holmes, David; Jeong, Myung Ho; Legrand, Victor; Neumann, Franz-Josef; Nyakern, Maria; Spaulding, Christian; Worthley, Stephen

    2011-03-29

    The aim of this study was to ascertain the 1-year incidence of stent thrombosis (ST) and major bleeding (MB) in a large, unselected population treated with sirolimus-eluting stents (SES). Stent thrombosis and MB are major potential complications of drug-eluting stent implantation. Their relative incidence and predisposing factors among large populations treated worldwide are unclear. The SES were implanted in 15,147 patients who were entered in a multinational registry. We analyzed the incidence of: 1) definite and probable ST as defined by the Academic Research Consortium; and 2) MB, with the STEEPLE (Safety and efficacy of Enoxaparin in PCI) definition, together with their relation to dual antiplatelet therapy (DAPT) and to 1-year clinical outcomes. The mean age of the sample was 62 ± 11 years, 30.4% were diabetic, 10% had a Charlson comorbidity index ≥3, and 44% presented with acute coronary syndrome or myocardial infarction. At 1 year, the reported compliance with DAPT as recommended by the European Society of Cardiology guidelines was 86.3%. Adverse event rates were: ST 1.0%, MB 1.0%, mortality 1.7%, myocardial infarction 1.9%, and target lesion revascularization 2.3%. Multivariate analysis identified 9 correlates of ST and 4 correlates of MB. Advanced age and a high Charlson index were associated with an increased risk of both ST and MB. After ST, the 7-day and 1-year all-cause mortality was 30% and 35%, respectively, versus 1.5% and 10% after MB. Only 2 of 13,749 patients (0.015%) experienced both MB and ST during the entire 1-year follow-up period. In this worldwide population treated with ≥1 SES, the reported compliance with DAPT was good, and the incidence of ST and MB was low. Stent thrombosis and MB very rarely occurred in the same patient. (The e-SELECT Registry: a Multicenter Post-Market Surveillance; NCT00438919). Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  7. The Effect of Cilostazol on the Angiographic Outcome of Drug-Eluting Coronary Stents Angiographic Analysis of the CILON-T (Influence of CILostazol-Based Triple Antiplatelet Therapy ON Ischemi Complication after Drug-Eluting StenT Implantation) Trial.

    Science.gov (United States)

    Suh, Jung-Won; Lee, Seung-Pyo; Park, KyungWoo; Kang, Hyun-Jae; Koo, Bon-Kwon; Cho, Young-Seok; Youn, Tae-Jin; Chae, In-Ho; Choi, Dong-Ju; Rha, Seung-Woon; Bae, Jang-Ho; Kwon, Taek-Geun; Bae, Jang-Whan; Cho, Myeong-Chan; Kim, Hyo-Soo

    2017-12-12

    It is not clear if anti-restonotic effect of cilostazol is consistent for different types of drug-eluting stents (DES).The purpose of this study was to compare the anti-proliferative effect of cilostazol between DAT and TAT with consideration of confounding influences of DES type.Nine hundred and fifteen patients were randomized to either dual antiplatelet therapy (DAT; aspirin and clopidogrel) or triple antiplatelet therapy (TAT; aspirin, clopidogrel, and cilostazol) in the previous CILON-T trial. After excluding 70 patients who received both or neither stents, we analyzed 845 patients who received exclusively PES or ZES, and compared in-stent late loss at 6 months between both antiplatelet regimens (DAT versus TAT).Baseline angiographic and clinical characteristics were similar between the DAT (656 lesions in 425 patients) and the TAT group (600 lesions in 420 patients). The 6-month follow-up angiography was completed in 745 patients (88.2%). Quantitative coronary angiography showed that TAT significantly reduced in-stent late loss (DAT 0.62 ± 0.62 mm versus TAT 0.54 ± 0.49 mm, P = 0.015). Stent type, diabetes or lesion length did not interact with difference of late loss. However, reduction of late loss by cilostazol did not lead to a significant reduction in the rate of target lesion revascularization (TLR) (DAT 7.8% versus TAT 6.9%, P = 0.69) due to a nonlinear relationship found between late loss and TLR.The TAT group showed less in-stent late loss as compared to the DAT group. This was consistently observed regardless of DES type, lesion length, or diabetic status. However, reduction of late loss by cilostazol did not lead to a significant reduction in TLR.

  8. Everolimus for Advanced Pancreatic Neuroendocrine Tumors.

    NARCIS (Netherlands)

    Yao, James C.; Shah, Manisha H.; Ito, Tetsuhide; Bohas, Catherine Lombard; Wolin, Edward M.; Van Cutsem, Eric; Hobday, Timothy J.; Okusaka, Takuji; Capdevila, Jaume; de Vries, Elisabeth G. E.; Tomassetti, Paola; Pavel, Marianne E.; Hoosen, Sakina; Haas, Tomas; Lincy, Jeremie; Lebwohl, David; Oberg, Kjell

    2011-01-01

    Background: Everolimus, an oral inhibitor of mammalian target of rapamycin (mTOR), has shown antitumor activity in patients with advanced pancreatic neuroendocrine tumors, in two phase 2 studies. We evaluated the agent in a prospective, randomized, phase 3 study. Methods: We randomly assigned 410

  9. Late lumen loss and intima hyperplasia after sirolimus-eluting and zotarolimus-eluting stent implantation in diabetic patients: the diabetes and drug-eluting stent (DiabeDES III) angiography and intravascular ultrasound trial

    DEFF Research Database (Denmark)

    Jensen, Lisette Okkels; Mæng, Michael; Thayssen, Per

    2011-01-01

    Patients with diabetes mellitus have increased risk of in-stent restenosis after coronary stent implantation due to neointimal hyperplasia (NIH). The aim of this study was to use quantitative coronary angiography (QCA) and volumetric intravascular ultrasound (IVUS) to evaluate the effects...... of the sirolimus-eluting Cypher® stent (SES) and the zotarolimus-eluting Endeavor® stent (ZES) on angiographic late lumen loss and intima hyperplasia in diabetic patients....

  10. Percutaneous coronary intervention versus coronary-artery bypass grafting for severe coronary artery disease

    NARCIS (Netherlands)

    P.W.J.C. Serruys (Patrick); M-C. Morice (Marie-Claude); A.P. Kappetein (Arie Pieter); A. Colombo (Antonio); D.R. Holmes Jr (David); M.J. Mack (Michael); E. Stahle (Elisabeth); T.E. Feldman (Ted); M.J.B.M. van den Brand (Marcel); E.J. Bass (Eric); N. van Dyck (Nic); K. Leadly (Katrin); K.D. Dawkins (Keith); F.W. Mohr (Friedrich)

    2009-01-01

    textabstractBACKGROUND Percutaneous coronary intervention (PCI) involving drug-eluting stents is increasingly used to treat complex coronary artery disease, although coronary-artery bypass grafting (CABG) has been the treatment of choice historically. Our trial compared PCI and CABG for treating

  11. Regression of Cardiac Rhabdomyomas in a Neonate after Everolimus Treatment

    Directory of Open Access Journals (Sweden)

    Helen Bornaun

    2016-01-01

    Full Text Available Cardiac rhabdomyoma often shows spontaneous regression and usually requires only close follow-up. However, patients with symptomatic inoperable rhabdomyomas may be candidates for everolimus treatment. Our patient had multiple inoperable cardiac rhabdomyomas causing serious left ventricle outflow-tract obstruction that showed a dramatic reduction in the size after everolimus therapy, a mammalian target of rapamycin (mTOR inhibitor. After discontinuation of therapy, an increase in the diameter of masses occurred and everolimus was restarted. After 6 months of treatment, rhabdomyomas decreased in size and therapy was stopped. In conclusion, everolimus could be a possible novel therapy for neonates with clinically significant rhabdomyomas.

  12. Comparison of paclitaxel- and sirolimus-eluting stents in everyday clinical practice: the SORT OUT II randomized trial

    DEFF Research Database (Denmark)

    Galløe, Anders M; Thuesen, Leif; Kelbaek, Henning

    2008-01-01

    Approval of drug-eluting coronary stents was based on results of relatively small trials of selected patients; however, in routine practice, stents are used in a broader spectrum of patients.......Approval of drug-eluting coronary stents was based on results of relatively small trials of selected patients; however, in routine practice, stents are used in a broader spectrum of patients....

  13. In vivo serial invasive imaging of the second-generation drug-eluting absorbable metal scaffold (Magmaris - DREAMS 2G) in de novo coronary lesions: Insights from the BIOSOLVE-II First-In-Man Trial.

    Science.gov (United States)

    Garcia-Garcia, Hector M; Haude, Michael; Kuku, Kayode; Hideo-Kajita, Alexandre; Ince, Hüseyin; Abizaid, Alexandre; Tölg, Ralph; Lemos, Pedro Alves; von Birgelen, Clemens; Christiansen, Evald Høj; Wijns, William; Escaned, Javier; Dijkstra, Jouke; Waksman, Ron

    2018-03-15

    Bioresorbable scaffolds may confer clinical benefit in long-term studies; early mechanistic studies using intravascular imaging have provided insightful information about the immediate and mid-term local serial effects of BRS on the coronary vessel wall. We assessed baseline, 6- and 12-month imaging data of the drug-eluting absorbable metal scaffold (DREAMS 2G). The international, first-in-man BIOSOLVE-II trial enrolled 123 patients with up to 2 de novo lesions (in vessels of 2.2 to 3.7mm). Angiographic based vasomotion, curvature and angulation were assessed; intravascular ultrasound (IVUS) derived radiofrequency (RF) data analysis and echogenicity were evaluated; optical coherence tomography (OCT) attenuation and backscattering analysis were also performed. There was hardly any difference in curvature between pre-procedure and 12months (-0.0019; p=0.48). The change in angulation from pre- to 12months was negligible (-3.58°; 95% CI [-5.97, -1.20]), but statistically significant. At 6months, the change in QCA based minimum lumen diameter in response to high dose of acetylcholine and IVUS-RF necrotic core percentage showed an inverse relationship (estimate of -0.489; p=0.055) and with fibrous volume a positive relationship (estimate of 0.53, p=0.035). Bioresorption analysis by OCT showed that the maximum attenuation values decreased significantly from post-procedure at 6months (Δ 6months vs. post-proc. is -13.5 [95% CI -14.6, -12.4]) and at 12months (Δ 12months vs. post-proc. is -14.0 [95% CI -15.4, -12.6]). By radiofrequency data, the percentage of dense calcium decreased significantly from post-procedure at 6months and at 12months. Likewise, by echogenicity, hyperechogenic structures decreased significantly from post-procedure at 6months; thereafter, they remained unchanged. Following implantation of DREAMS 2G, restoration of the vessel geometry, vasomotion and bioresorption signs were observed at up to 12months; importantly, these changes occurred with

  14. Coated stents to prevent restenosis in coronary heart disease

    Directory of Open Access Journals (Sweden)

    Hagen, Anja

    2005-11-01

    Full Text Available Background: In-stent-restenosis (ISR is considered to be an essential limiting factor of stenting in coronary heart disease (CHD. The development of coated stents has raised expectations on substantial lowering restenosis after stenting with decreasing the rate of restenosis and a reduction in the rate of clinical events. Objectives: The present analysis addresses the questions on medical effectiveness and cost-effectiveness of the use of various coated stent types in CHD. Methods: The literature was searched in December 2004 in the most relevant medical and economic databases. The medical evaluation was conducted on the basis of published RCT. The data from the studies regarding various angiographic, sonographic and clinical endpoints were checked for methodical quality and summarised in meta-analyses. Within the scope of economic evaluation the primary studies were analysed and modelling was performed, applying clinical effect estimates from the meta-analyses of the medical evaluation and current estimates of German costs. Results: Medical evaluation: Ten different stenttypes were used in the included 26 RCT. The results for heparin, silicon-carbide, carbon and PTFE coated stenttypes could not reveal any significant differences between the medical effectiveness of coated and uncoated stents. The application of sirolimus, paclitaxel, everolimus and 7-hexanoyltaxol eluting stents showed a significant lower restenosis at 6-9 months with decrease in the rate of restenosis for polymer-based sirolimus, paclitaxel and 7-hexanoyltaxol eluting stents. In contrast, the use of gold-coated and actinomycin-D eluting stents was associated with a significantly higher restenosis. The polymer-based sirolimus and paclitaxel eluting stents also showed a significant and considerable reduction in the rate of repeated percutaneous revascularisations at 6-12 months (3.5% vs. 19.7%; p<0.0001, RR=0.19 [95%CI: 0.11; 0.33] and 3.5% vs. 12.2%; p<0.0001, RR=0.30 [95%CI: 0

  15. First-in-human evaluation of a bioabsorbable polymer-coated sirolimus-eluting stent: imaging and clinical results of the DESSOLVE I Trial (DES with sirolimus and a bioabsorbable polymer for the treatment of patients with de novo lesion in the native coronary arteries).

    Science.gov (United States)

    Ormiston, John; Webster, Mark; Stewart, James; Vrolix, Mathias; Whitbourn, Robert; Donohoe, Dennis; Knape, Charlene; Lansky, Alexandra; Attizzani, Guilherme F; Fitzgerald, Peter; Kandzari, David E; Wijns, William

    2013-10-01

    This first-in-human multicenter study sought to examine prospectively the safety and efficacy of a new, cobalt chromium thin-strut, coronary absorbable polymer-coated, sirolimus-eluting stent. Bioabsorbable polymers on drug-eluting stents may lower the long-term risks of inflammation, delayed healing, and adverse events. We enrolled patients with symptomatic coronary artery disease with stable or unstable angina pectoris and >50% diameter stenosis, amenable to coverage with a ≤23-mm long stent in a vessel 2.5 to 3.5 mm in diameter. All patients received dual antiplatelet therapy after implantation. Patients, in groups of 10, underwent repeat angiography, intravascular ultrasound, and optical coherence tomography at 4, 6, or 8 months, and all patients were seen or contacted at 18 months of follow-up. The median (range) in-stent late lumen loss (LLL) was 0.03 mm (-0.22 to 0.21 mm), 0.10 mm (-0.03 to 1.2 mm), and 0.08 mm (-0.01 to 0.28 mm), at 4, 6, and 8 months, respectively. At 18 months, the median in-stent LLL was 0.08 mm (-0.30 to 0.46 mm). On optical coherence tomography, the proportion of uncovered stent struts decreased from a median of 7.3% (range 0.4% to 46.3%) at 4 months to 0% (range: 0% to 3.4%) at 18 months. The percentage of neointimal volume obstruction by intravascular ultrasound increased from a median of 5.3% to 9.1% between 4 and 6 months and remained nearly unchanged thereafter through 18 months of follow-up. The only recorded major adverse cardiac event was a myocardial infarction. At 18 months of follow-up, this absorbable polymer-coated, cobalt chromium sirolimus-eluting stent was associated with a low and stable in-stent LLL, complete strut coverage, and no stent thrombosis. (First-In-Human Trial of the MiStent Drug-Eluting Stent [DES] in Coronary Artery Disease [DESSOLVE-I]; NCT01247428). Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  16. Drug-eluting stents to prevent stent thrombosis and restenosis.

    Science.gov (United States)

    Im, Eui; Hong, Myeong-Ki

    2016-01-01

    Although first-generation drug-eluting stents (DES) have significantly reduced the risk of in-stent restenosis, they have also increased the long-term risk of stent thrombosis. This safety concern directly triggered the development of new generation DES, with innovations in stent platforms, polymers, and anti-proliferative drugs. Stent platform materials have evolved from stainless steel to cobalt or platinum-chromium alloys with an improved strut design. Drug-carrying polymers have become biocompatible or biodegradable and even polymer-free DES were introduced. New limus-family drugs (such as everolimus, zotarolimus or biolimus) were adopted to enhance stent performances. As a result, these new DES demonstrated superior vascular healing responses on intracoronary imaging studies and lower stent thrombotic events in actual patients. Recently, fully-bioresorbable stents (scaffolds) have been introduced, and expanding their applications. In this article, the important concepts and clinical results of new generation DES and bioresorbable scaffolds are described.

  17. The Role of Everolimus in Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Malek Meskawi

    2015-12-01

    Full Text Available Everolimus (RAD001 is an orally administered agent that inhibits the mammalian target of rapamycin serine-threonine kinase. A phase III pivotal trial on everolimus, published in 2008, provided the first evidence for the efficacy of sequential therapy for patients with metastatic clear cell renal cell carcinoma (RCC. In this study, everolimus was used after failure of one or several previous lines of therapy, and it demonstrated a 3-month survival benefit relative to placebo. Currently, based on the level 1 evidence, everolimus represents the molecule of choice for third-line therapy after failure of previous two tyrosine kinase inhibitors (TKIs. However, second-line use after failure of one TKI is challenged by two new molecules (nivolumab and cabozantinib, which proved to have better efficacy with similar toxicity profile. In non-clear cell metastatic RCC, the current evidence recommends everolimus as a second-line therapy after failure of previous first-line sunitinib.

  18. The 'Harmonizing Optimal Strategy for Treatment of coronary artery stenosis - sAfety & effectiveneSS of drug-elUting stents & antiplatelet REgimen' (HOST-ASSURE trial: study protocol for a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Park Kyung

    2012-03-01

    Full Text Available Abstract Background Second-generation drug-eluting stents (DES have raised the bar of clinical performance. These stents are mostly made from cobalt chromium alloy. A newer generation DES has been developed from platinum chromium alloy, but clinical data regarding the efficacy and safety of the platinum chromium-based everolimus-eluting stent (PtCr-EES is limited, with no comparison data against the cobalt chromium-based zotarolimus-eluting stent (CoCr-ZES. In addition, an antiplatelet regimen is an integral component of medical therapy after percutaneous coronary intervention (PCI. A 1-week duration of doubling the dose of clopidogrel (double-dose antiplatelet therapy (DDAT was shown to improve outcome at 1 month compared with conventional dose in acute coronary syndrome (ACS patients undergoing PCI. However in Asia, including Korea, the addition of cilostazol (triplet antiplatelet therapy (TAT is used more commonly than doubling the dose of clopidogrel in high-risk patients. Methods In the 'Harmonizing Optimal Strategy for Treatment of coronary artery stenosis - sAfety & effectiveneSS of drug-elUting stents & antiplatelet REgimen' (HOST-ASSURE trial, approximately 3,750 patients are being prospectively and randomly assigned in a 2 × 2 factorial design according to the type of stent (PtCr-EES vs CoCr-ZES and antiplatelet regimen (TAT vs DDAT. The first primary endpoint is target lesion failure at 1 year for the stent comparison, and the second primary endpoint is net clinical outcome at 1 month for comparison of antiplatelet therapy regimen. Discussion The HOST-ASSURE trial is the largest study yet performed to directly compare the efficacy and safety of the PtCr-EES versus CoCr-ZES in an 'all-comers' population. In addition, this study will also compare the clinical outcome of TAT versus DDAT for 1-month post PCI. Trial registration ClincalTrials.gov number NCT01267734.

  19. Serial 5-Year Evaluation of Side Branches Jailed by Bioresorbable Vascular Scaffolds Using 3-Dimensional Optical Coherence Tomography: Insights From the ABSORB Cohort B Trial (A Clinical Evaluation of the Bioabsorbable Everolimus Eluting Coronary Stent System in the Treatment of Patients With De Novo Native Coronary Artery Lesions)

    NARCIS (Netherlands)

    Onuma, Y.; Grundeken, M.J.; Nakatani, S.; Asano, T.; Sotomi, Y.; Foin, N.; Ng, J.; Okamura, T.; Wykrzykowska, J.J.; Winter, R.J. de; Geuns, R.J.M. van; Koolen, J.; Christiansen, E.; Whitbourn, R.; McClean, D.; Smits, P; Windecker, S.; Ormiston, J.A.; Serruys, P.W.

    2017-01-01

    BACKGROUND: The long-term fate of Absorb bioresorbable vascular scaffold (Abbott Vascular, Santa Clara, CA) struts jailing side branch ostia has not been clarified. We therefore evaluate serially (post-procedure and at 6 months, 1, 2, 3, and 5 years) the appearance and fate of jailed Absorb

  20. Serial 5-Year Evaluation of Side Branches Jailed by Bioresorbable Vascular Scaffolds Using 3-Dimensional Optical Coherence Tomography Insights From the ABSORB Cohort B Trial (A Clinical Evaluation of the Bioabsorbable Everolimus Eluting Coronary Stent System in the Treatment of Patients With De Novo Native Coronary Artery Lesions)

    NARCIS (Netherlands)

    Onuma, Yoshinobu; Grundeken, Maik J.; Nakatani, Shimpei; Asano, Taku; Sotomi, Yohei; Foin, Nicolas; Ng, Jaryl; Okamura, Takayuki; Wykrzykowska, Joanna J.; de Winter, Robbert J.; van Geuns, Robert-Jan; Koolen, Jacques; Christiansen, Evald; Whitbourn, Robert; McClean, Dougal; Smits, Pieter; Windecker, Stephan; Ormiston, John A.; Serruys, Patrick W.

    2017-01-01

    Background-The long-term fate of Absorb bioresorbable vascular scaffold (Abbott Vascular, Santa Clara, CA) struts jailing side branch ostia has not been clarified. We therefore evaluate serially (post-procedure and at 6 months, 1, 2, 3, and 5 years) the appearance and fate of jailed Absorb

  1. Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma

    DEFF Research Database (Denmark)

    Motzer, Robert J; Escudier, Bernard; McDermott, David F

    2015-01-01

    BACKGROUND: Nivolumab, a programmed death 1 (PD-1) checkpoint inhibitor, was associated with encouraging overall survival in uncontrolled studies involving previously treated patients with advanced renal-cell carcinoma. This randomized, open-label, phase 3 study compared nivolumab with everolimus...... of nivolumab per kilogram of body weight intravenously every 2 weeks or a 10-mg everolimus tablet orally once daily. The primary end point was overall survival. The secondary end points included the objective response rate and safety. RESULTS: The median overall survival was 25.0 months (95% confidence...... interval [CI], 21.8 to not estimable) with nivolumab and 19.6 months (95% CI, 17.6 to 23.1) with everolimus. The hazard ratio for death with nivolumab versus everolimus was 0.73 (98.5% CI, 0.57 to 0.93; P=0.002), which met the prespecified criterion for superiority (P≤0.0148). The objective response rate...

  2. Safety and efficacy of low-dose paclitaxel utilizing the cobra-P drug-eluting stent system with a novel biodegradable coating in de novo coronary lesions: the PLUS-ONE first-in-man study.

    Science.gov (United States)

    Calderas, Carlos; Condado, Jose Francisco; Condado, Jose Antonio; Flores, Alejandra; Mueller, Amy; Thomas, Jack; Nakatani, Daisaku; Honda, Yasuhiro; Waseda, Katsuhisa; Fitzgerald, Peter

    2014-01-01

    The Cobra-P drug-eluting stent (DES) system consists of cobalt chromium alloy with bio-absorbable siloxane sol-gel matrix coating that elutes low dose paclitaxel within 6 months. The aim of this first-in-man trial was to evaluate the safety and performance of 2 doses of the Cobra-P DES. A total of 60 lesions (54 patients) were sequentially assigned to 2 different paclitaxel doses: group A (3.7 μg/18mm, n=30) or group B (8 μg/18mm, n=30). The primary endpoint was MACE at 4 months defined as cardiac death, myocardial infarction, and target lesion revascularization. Patient and lesion characteristics were matched between the 2 groups except for male sex. MACE at 4 months was 3.3% and 0% respectively (P=1.000) and at 1-year follow-up remained unchanged. In-stent late loss at 4 months was similar in both groups (0.36 ± 0.30mm and 0.34 ± 0.20mm P=.773). In this FIM study, implantation of the Cobra-P low dose paclitaxel-eluting stent with a bioabsorbable sol-gel coating was proven to be feasible and safe. Moderate neointimal proliferation was observed as well as an acceptable MACE rate up to 1 year. © 2014.

  3. Safety and efficacy of low-dose paclitaxel utilizing the cobra-P drug-eluting stent system with a novel biodegradable coating in de novo coronary lesions: The PLUS-ONE first-in-man study

    Energy Technology Data Exchange (ETDEWEB)

    Calderas, Carlos [Instituto de Clinicas Urologia Tamanaco, Caracas (Venezuela, Bolivarian Republic of); Condado, Jose Francisco; Condado, Jose Antonio [Hospital Centro Medico de Caracas y Hospital Miguel Perez Carreno, Caracas (Venezuela, Bolivarian Republic of); Flores, Alejandra [Instituto de Clinicas Urologia Tamanaco, Caracas (Venezuela, Bolivarian Republic of); Mueller, Amy; Thomas, Jack [Medlogics Device Corporation, Santa Rosa, CA (United States); Nakatani, Daisaku; Honda, Yasuhiro; Waseda, Katsuhisa [Stanford University, Stanford, CA (United States); Fitzgerald, Peter, E-mail: crci-cvmed@stanford.edu [Stanford University, Stanford, CA (United States)

    2014-01-15

    Background: The Cobra-P drug-eluting stent (DES) system consists of cobalt chromium alloy with bio-absorbable siloxane sol–gel matrix coating that elutes low dose paclitaxel within 6 months. The aim of this first-in-man trial was to evaluate the safety and performance of 2 doses of the Cobra-P DES. Methods: A total of 60 lesions (54 patients) were sequentially assigned to 2 different paclitaxel doses: group A (3.7 μg/18 mm, n = 30) or group B (8 μg/18 mm, n = 30). The primary endpoint was MACE at 4 months defined as cardiac death, myocardial infarction, and target lesion revascularization. Results: Patient and lesion characteristics were matched between the 2 groups except for male sex. MACE at 4 months was 3.3% and 0% respectively (P = 1.000) and at 1-year follow-up remained unchanged. In-stent late loss at 4 months was similar in both groups (0.36 ± 0.30 mm and 0.34 ± 0.20 mm P = .773). Conclusions: In this FIM study, implantation of the Cobra-P low dose paclitaxel-eluting stent with a bioabsorbable sol–gel coating was proven to be feasible and safe. Moderate neointimal proliferation was observed as well as an acceptable MACE rate up to 1 year.

  4. Safety and efficacy of low-dose paclitaxel utilizing the cobra-P drug-eluting stent system with a novel biodegradable coating in de novo coronary lesions: The PLUS-ONE first-in-man study

    International Nuclear Information System (INIS)

    Calderas, Carlos; Condado, Jose Francisco; Condado, Jose Antonio; Flores, Alejandra; Mueller, Amy; Thomas, Jack; Nakatani, Daisaku; Honda, Yasuhiro; Waseda, Katsuhisa; Fitzgerald, Peter

    2014-01-01

    Background: The Cobra-P drug-eluting stent (DES) system consists of cobalt chromium alloy with bio-absorbable siloxane sol–gel matrix coating that elutes low dose paclitaxel within 6 months. The aim of this first-in-man trial was to evaluate the safety and performance of 2 doses of the Cobra-P DES. Methods: A total of 60 lesions (54 patients) were sequentially assigned to 2 different paclitaxel doses: group A (3.7 μg/18 mm, n = 30) or group B (8 μg/18 mm, n = 30). The primary endpoint was MACE at 4 months defined as cardiac death, myocardial infarction, and target lesion revascularization. Results: Patient and lesion characteristics were matched between the 2 groups except for male sex. MACE at 4 months was 3.3% and 0% respectively (P = 1.000) and at 1-year follow-up remained unchanged. In-stent late loss at 4 months was similar in both groups (0.36 ± 0.30 mm and 0.34 ± 0.20 mm P = .773). Conclusions: In this FIM study, implantation of the Cobra-P low dose paclitaxel-eluting stent with a bioabsorbable sol–gel coating was proven to be feasible and safe. Moderate neointimal proliferation was observed as well as an acceptable MACE rate up to 1 year

  5. Research and innovation in the development of everolimus for oncology.

    Science.gov (United States)

    Lebwohl, David; Thomas, George; Lane, Heidi A; O'Reilly, Terence; Escudier, Bernard; Yao, James C; Pavel, Marianne; Franz, David; Berg, William; Baladi, Jean-Francois; Stewart, Jubilee; Motzer, Robert J

    2011-03-01

    The critical role of increased activity of mammalian target of rapamycin (mTOR) in the pathophysiology of multiple diseases is well established. Inhibition of the mTOR pathway may block disease progression and improve patient outcomes. Everolimus, an mTOR inhibitor, began in clinical development as part of a regimen (Certican, Zortress) for prevention of organ transplant rejection and is now an approved oncology agent. The objective of this review is to discuss the history of key findings and innovative cancer research undertaken to successfully develop everolimus as an oncology therapy (Afinitor) now approved for patients with advanced renal cell carcinoma (RCC) and for subependymal giant cell astrocytomas (SEGAs) associated with tuberous sclerosis. In addition, data for the use of everolimus in the treatment of other cancers and rare diseases are also discussed. A PubMed search of English articles without time restrictions was conducted using the search terms 'everolimus or rapamycin' and 'cancer'. Bibliographies of retrieved articles were manually searched for additional relevant articles. Major cancer congresses were also searched. The clinical efficacy of everolimus alone and in combination with other agents has been observed in recently completed Phase II-III studies in a wide spectrum of tumors, including RCC, neuroendocrine tumors, tuberous sclerosis complex, SEGAs and angiomyolipomas, lymphoma and gastric, breast and hepatocellular cancers. These findings emphasize the importance of mTOR in diverse cancers and rare diseases and underscore the potential role for everolimus as an effective agent in multiple indications.

  6. Effect of trimetazidine on recurrent angina pectoris and left ventricular structure in elderly multivessel coronary heart disease patients with diabetes mellitus after drug-eluting stent implantation: a single-centre, prospective, randomized, double-blind study at 2-year follow-up.

    Science.gov (United States)

    Xu, Xiaohan; Zhang, Weijun; Zhou, Yujie; Zhao, Yingxin; Liu, Yuyang; Shi, Dongmei; Zhou, Zhiming; Ma, Hanying; Wang, Zhijian; Yu, Miao; Ma, Qian; Gao, Fei; Shen, Hua; Zhang, Jianwei

    2014-04-01

    Trimetazidine has been shown to improve angina pectoris and left ventricular (LV) function in diabetic patients with ischaemic cardiomyopathy. The objective of this study was to evaluate the effects of trimetazidine on recurrent angina pectoris and LV structure after drug-eluting stent (DES) implantation in elderly multivessel coronary heart disease (CHD) patients with diabetes mellitus (DM) and a left ventricular ejection fraction (LVEF) of ≥ 50 %. This was a single-centre, prospective, randomized, double-blind evaluation study. Between January 2010 and September 2010, 700 CHD patients with DM who were aged ≥ 65 years and undergoing coronary angiography at An Zhen Hospital (Beijing, China) were recruited and prospectively randomized to receive trimetazidine (20 mg three times daily) or placebo after DES implantation as an addition to conventional CHD treatment. The primary end points were the incidence of recurrent angina pectoris and measures of various echocardiographic parameters, which included LVEF. At 2-year follow-up, patients in the trimetazidine group (n = 255) showed significant improvements in the incidence (P = 0.024) and severity of angina pectoris, compared with the control group, as well as silent myocardial ischaemia (P = 0.009) and angina pectoris-free survival (P = 0.011). LV function and structure in trimetazidine-treated patients were relatively stable at 2-year follow-up, while they deteriorated in the control group (n = 255) with a significant difference between groups (all P angina pectoris as well as LV function and structure in elderly multivessel CHD patients with DM.

  7. Improvement in renal function after everolimus introduction and calcineurin inhibitor reduction in maintenance thoracic transplant recipients

    DEFF Research Database (Denmark)

    Arora, Satish; Gude, Einar; Sigurdardottir, Vilborg

    2012-01-01

    The NOCTET (NOrdic Certican Trial in HEart and lung Transplantation) trial demonstrated that everolimus improves renal function in maintenance thoracic transplant (TTx) recipients. Nevertheless, introduction of everolimus is not recommended for patients with advanced renal failure. We evaluated...... NOCTET data to assess everolimus introduction amongst TTx recipients with advanced renal failure....

  8. Renal function three years after early conversion from a calcineurin inhibitor to everolimus

    DEFF Research Database (Denmark)

    Mjörnstedt, Lars; Schwartz Sørensen, Søren; von Zur Mühlen, Bengt

    2015-01-01

    In a 36-month, open-label, multicenter trial, 202 kidney transplant recipients were randomized at week 7 post-transplant to convert to everolimus or remain on cyclosporine: 182 were analyzed to month 36 (92 everolimus, 90 controls). Mean (SD) change in measured GFR (mGFR) from randomization to mo......, but discontinuation was more frequent with everolimus (33.7% vs. 10.0%). Conversion from cyclosporine to everolimus at 7 weeks post-transplant was associated with a significant benefit in renal function at 3 years when everolimus was continued....

  9. Everolimus Implicated in Case of Severe Gastrointestinal Hemorrhage

    Directory of Open Access Journals (Sweden)

    Paul Gonzales

    2017-01-01

    Full Text Available Breast cancer remains the leading cause of cancer and the third leading cause of cancer related deaths among our population with an estimated number of 246,660 new cases and 40,450 deaths in 2016. With treatment advancements, including targeted agents such as Everolimus, a mammalian target of rapamycin (mTOR inhibitor, survivability and quality of life continue to improve. However, with the use of these agents come adverse effects, some of which are still being characterized. Our case demonstrates recurrent episodes of gastrointestinal bleeding in a 60-year-old woman being treated with Everolimus for progressive metastatic breast cancer. On endoscopy, bleeding was secondary to erosive gastritis. Previous case reports have described bleeding due to gastric antral vascular ectasia (GAVE, which was described in two prior reported cases. In our case, bleeding also occurred on a reduced dose of Everolimus compared to what is previously reported (5 mg versus 10 mg. As a result of her gastrointestinal bleeding, she required multiple endoscopic interventions including argon plasma coagulation and multipolar heater probe to achieve hemostasis. This is the first case reported of gastrointestinal bleeding not consistent with GAVE and occurring while being on a reduced dose of Everolimus. It is important to document our case so that the Gastroenterology and Hematology communities can be educated and made aware for their patient populations on Everolimus.

  10. Optical Coherence Tomography Substudy of A Prospective Multicenter Randomized Post-Market Trial to Assess the Safety and Effectiveness of the Firehawk™ Rapamycin Target Eluting Cobalt Chromium Coronary Stent System for the Treatment of Atherosclerotic Lesions: TARGET All Comers.

    Science.gov (United States)

    Baumbach, Andreas; Lansky, Alexandra J; Onuma, Yoshi; Asano, Taku; Johnson, Thomas; Anderson, Richard; Kiemeneij, Ferdinand; Zheng, Ming; Van Royen, Niels; Slagboom, Ton; Vlachojannis, Georg; Xu, Bo; Serruys, Patrick; Wijns, William

    2018-06-12

    Durable polymer drug-eluting stents (DP DES) may contribute to persistent inflammation, delayed endothelial healing and subsequent late DES thrombosis. The aim of this Optical Coherence Tomography (OCT) sub-study was to compare healing and neointimal coverage of a novel bioabsorbable polymer sirolimus-eluting stent (FIREHAWK®) (BP DES) versus the DP DES (XIENCE) at 90 days in an all comers patient population. The TARGET All Comers study is a prospective multicenter randomised post-market trial of 1656 patients randomised 1:1 to FIREHAWK or XIENCE at 21 centers in 10 European countries. The TARGET OCT sub-study enrolled 36 consecutive patients with 52 lesions at 6 centers proficient in OCT. Follow-up OCT was performed at 3 months or prior to revascularisation when occurring before the 3-month window. The substudy was designed for non-inferiority of the primary endpoint of neointimal thickness. At follow-up, the mean neointimal thickness by OCT (52 lesions, Firehawk, n=24; Xience, n=28), was not significantly different between groups (Firehawk 75.5μm vs Xience V 82.3 μm) meeting the primary endpoint of non-inferiority (Pnoninferiority<0.001). The percentage of stent strut coverage was high in both groups (strut level: 99.9% ± 0.3 vs 100% ± 0.1, p=0.26), and the proportion of malapposed struts (1.0±1.6% vs. 1.2±2.0%, p=0.51) was low in both groups. Based on OCT, the FIREHAWK BP DES has a similar healing response 3 months after implantation compared to the DP DES, with near complete strut coverage, moderate neointima formation and minimal strut malapposition.

  11. Stent Coating Integrity of Durable and Biodegradable Coated Drug Eluting Stents.

    Science.gov (United States)

    Yazdani, Saami K; Sheehy, Alexander; Pacetti, Stephen; Rittlemeyer, Brandon; Kolodgie, Frank D; Virmani, Renu

    2016-10-01

    Coatings consisting of a polymer and drug are widely used in drug-eluting stents (DES) and are essential in providing programmable drug release kinetics. Among other factors, stent coating technologies can influence blood compatibility, affect acute and sub-acute healing, and potentially trigger a chronic inflammatory response. The aim of this study was to investigate the short-term (7 and 28 days) and long-term (90 and 180 days) coating integrity of the Xience Prime Everolimus-Eluting Stent (EES), Resolute Zotarolimus-Eluting Stent (ZES), Taxus Paclitaxel-Eluting Stent (PES), and Nobori Biolimus A9-Eluting Stent (BES) in a rabbit ilio-femoral stent model. Stented arteries (n = 48) were harvested and the tissue surrounding the implanted stents digested away with an enzymatic solution. Results demonstrated that the majority of struts of EES were without any coating defects with a few struts showing minor defects. Similarly, for the ZES, most of the struts were without coating defects at all time points except at 180 days. The majority of PES demonstrated mostly webbing and uneven coating. In the BES group, the majority of strut coating showed polymer cracking. Overall, the EES and ZES had fewer coating defects than the PES and BES. Coating defects, however increase over time for the ZES, whereas the percent of coating irregularities remained constant for the EES. These results provide, for the first time, a comparison of the long-term durability of these drug-eluting stent coatings in vivo. © 2016, Wiley Periodicals, Inc.

  12. Recommendations of everolimus use in liver transplant.

    Science.gov (United States)

    Rubín Suárez, Angel; Bilbao Aguirre, Itxarone; Fernández-Castroagudin, Javier; Pons Miñano, José Antonio; Salcedo Plaza, Magdalena; Varo Pérez, Evaristo; Prieto Castillo, Martín

    2017-11-01

    Mammalian target of rapamycin (mTOR) inhibitors, everolimus (EVL) and sirolimus are immunosuppressive agents with a minor nephrotoxic effect, limited to the development of proteinuria in some cases. The combination of EVL and low-dose tacrolimus has proven to be as safe and effective as standard therapy with tacrolimus for the prevention of acute cellular rejection. Early initiation of EVL-based immunosuppressive regimens with reduced exposure to calcineurin inhibitors has been shown to significantly improve renal function of LT recipients during induction and maintenance phases, with comparable efficacy and safety profiles. In patients with established kidney failure, initiating EVL may enable clinicians to reduce calcineurin inhibitors exposure, thereby contributing to the improved renal function of these patients. Although there is not sufficient evidence to recommend their use to prevent the recurrence of hepatocellular carcinoma and the progression of de novo tumours, they are used in this context in routine clinical practice. Copyright © 2017 Elsevier España, S.L.U., AEEH y AEG. All rights reserved.

  13. gender-specific outcome after paclitaxel-eluting stent implantation in japanese patients with coronary artery disease--sub-analysis of the Japan TAXUS Express2 post-marketing survey.

    Science.gov (United States)

    Okura, Hiroyuki; Nakamura, Masato; Kotani, Jun-Ichi; Kozuma, Ken

    2013-01-01

     Although previous randomized and non-randomized studies have demonstrated the safety and efficacy of paclitaxel-eluting stents (PES), a higher revascularization rate has been reported in women than in men. A sub-analysis of the TAXUS Japan Post-market Surveillance Study (TAXUS-PMS) was done to assess the influence of gender on clinical outcome.  A total of 2,132 PES-treated Japanese patients (women, n=551) from this registry were analyzed. Subjects were stratified by gender to compare 1-year clinical outcome. PES-treated women were older and more likely to have insulin-treated diabetes and hypertension. In contrast, PES-treated men were more likely to be smokers, have a previous history of myocardial infarction, and lower ejection fraction. While cardiac death, myocardial infarction and stent thrombosis were similar between men and women, major cardiac events tended to be lower in women than in men (6.4% vs. 8.8%, P=0.08). Although women had significantly smaller reference vessel size (2.46±0.53 mm vs. 2.59±0.60 mm, Ptarget lesion revascularization rate was significantly lower in women than in men (4.2% vs. 6.5%, P<0.05).  Despite a higher risk profile, Japanese women treated with PES did not have a higher rate of repeat revascularization or major adverse clinical outcome than PES-treated men at 1 year. 

  14. Long-term clinical outcome in STEMI patients treated with primary PCI and drug-eluting or bare-metal stents: insights from a high-volume single-center registry

    DEFF Research Database (Denmark)

    Pedersen, Sune; Galatius, Soren; Mogelvang, Rasmus

    2011-01-01

    Use of drug-eluting stents (DES) in patients with ST-elevation myocardial infarction (STEMI) during routine primary percutaneous coronary intervention (pPCI) is controversial.......Use of drug-eluting stents (DES) in patients with ST-elevation myocardial infarction (STEMI) during routine primary percutaneous coronary intervention (pPCI) is controversial....

  15. Incidence, predicting factors, and clinical outcomes of periprocedural myocardial infarction after percutaneous coronary intervention for chronic total occlusion in the era of new-generation drug-eluting stents.

    Science.gov (United States)

    Kim, Jin-Ho; Kim, Byeong-Keuk; Kim, Seunghwan; Ahn, Chul-Min; Kim, Jung-Sun; Ko, Young-Guk; Choi, Donghoon; Hong, Myeong-Ki; Jang, Yangsoo

    2017-12-20

    This study aimed to examine predictors and clinical outcomes of periprocedural myocardial infarction (PMI) after chronic total occlusion (CTO) intervention. There are limited data on the clinical implications of PMI after CTO intervention in the new-generation drug-eluting stent (DES) era. We enrolled 337 patients who underwent CTO intervention and met the study criteria. We evaluated the incidence and predictors of PMI, defined as an increase in creatine kinase-MB ≥3× the upper limit of normal (ULN) after intervention and compared the occurrence rates of major adverse cardiac and cerebrovascular events (MACCE, defined as the composite of cardiac death, myocardial infarction, stent thrombosis, target-vessel revascularization, or cerebrovascular accidents) between the PMI and non-PMI groups. PMI occurred in 23 (6.8%) patients after CTO intervention. Significant independent predictors were previous bypass surgery [odds ratio (OR) = 5.52, 95% confidence interval (CI) = 1.17-25.92; P = 0.03], Japan-CTO score ≥3 (OR = 7.06, 95%CI = 2.57-19.39; P PMI group had a significantly higher MACCE rate than the non-PMI group (23.7 vs. 5.6%, P = 0.008 by log-rank test). PMI was an independent predictor of MACCE (HR = 4.26, 95%CI = 1.35-13.43; P = 0.01). The MACCE rate gradually increased in a CK-MB-dependent fashion and was highest in patients with ≥10× ULN (P = 0.005). Previous bypass surgery, high Japan-CTO score, side branch occlusion, and longer procedure time were strongly related to PMI occurrence after CTO intervention. PMI was significantly associated with worse clinical outcomes in the new-generation DES era. © 2017 Wiley Periodicals, Inc.

  16. Everolimus Alleviates Obstructive Hydrocephalus due to Subependymal Giant Cell Astrocytomas.

    Science.gov (United States)

    Moavero, Romina; Carai, Andrea; Mastronuzzi, Angela; Marciano, Sara; Graziola, Federica; Vigevano, Federico; Curatolo, Paolo

    2017-03-01

    Subependymal giant cell astrocytomas (SEGAs) are low-grade tumors affecting up to 20% of patients with tuberous sclerosis complex (TSC). Early neurosurgical resection has been the only standard treatment until few years ago when a better understanding of the molecular pathogenesis of TSC led to the use of mammalian target of rapamycin (mTOR) inhibitors. Surgical resection of SEGAs is still considered as the first line treatment in individuals with symptomatic hydrocephalus and intratumoral hemorrhage. We describe four patients with symptomatic or asymptomatic hydrocephalus who were successfully treated with the mTOR inhibitor everolimus. We collected the clinical data of four consecutive patients presenting with symptomatic or asymptomatic hydrocephalus due to a growth of subependymal giant cell atrocytomas and who could not undergo surgery for different reasons. All patients experienced a clinically significant response to everolimus and an early shrinkage of the SEGA with improvement in ventricular dilatation. Everolimus was well tolerated by all individuals. Our clinical series demonstrate a possible expanding indication for mTOR inhibition in TSC, which can be considered in patients with asymptomatic hydrocephalus or even when the symptoms already appeared. It offers a significant therapeutic alternative to individuals that once would have undergone immediate surgery. Everolimus might also allow postponement of a neurosurgical resection, making it elective with an overall lower risk. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Everolimus: a review of its pharmacologic properties and use in solid organ transplantation

    Directory of Open Access Journals (Sweden)

    Paul Huiras

    2011-10-01

    Full Text Available The aim of this review article is to review the pharmacology, pharmacokinetics, efficacy and safety of everolimus. Primary literature was obtained via MEDLINE. Studies and abstracts evaluating everolimus in solid organ transplantation were considered for evaluation. English-language studies and abstracts only were selected for inclusion. Everolimus, a proliferation signal inhibitor that prevents growth factor-induced cell proliferation, is effective in reducing the incidence of acute rejection in solid organ transplantation. This agent is also useful in reducing cyclosporine-related nephrotoxicity. Everolimus directly inhibits vascular remodelling and intimal thickening, which are often associated with chronic rejection. Clinical trials have shown that everolimus is generally safe. The most commonly reported adverse events were haematologic effects and hyperlipidaemia. Everolimus is the second proliferation signal inhibitor to be proven effective in preventing acute rejection in solid organ transplant recipients. However, its exact role in the transplant immunosuppressive armamentarium is still unknown.

  18. Everolimus initiation and early calcineurin inhibitor withdrawal in heart transplant recipients

    DEFF Research Database (Denmark)

    Andreassen, A K; Andersson, B; Gustafsson, F

    2014-01-01

    In a randomized, open-label trial, everolimus was compared to cyclosporine in 115 de novo heart transplant recipients. Patients were assigned within 5 days posttransplant to low-exposure everolimus (3–6 ng/mL) with reduced-exposure cyclosporine (n = 56), or standard-exposure cyclosporine (n = 59...... infection was less common with everolimus (5.4% vs. 30.5%, p heart transplantation. Since postoperative safety...

  19. Everolimus: a review of its pharmacologic properties and use in solid organ transplantation

    OpenAIRE

    Huiras, Paul; Gabardi, Steven

    2011-01-01

    The aim of this review article is to review the pharmacology, pharmacokinetics, efficacy and safety of everolimus. Primary literature was obtained via MEDLINE. Studies and abstracts evaluating everolimus in solid organ transplantation were considered for evaluation. English-language studies and abstracts only were selected for inclusion. Everolimus, a proliferation signal inhibitor that prevents growth factor-induced cell proliferation, is effective in reducing the incidence of acute rejectio...

  20. All-cause mortality after drug-eluting stent implantation in African-Americans.

    Science.gov (United States)

    Poludasu, Shyam; Cavusoglu, Erdal; Khan, Waqas; Marmur, Jonathan D

    2008-12-01

    Recent studies have questioned the safety of drug-eluting stents because of a higher incidence of late stent thrombosis, raising the possibility that drug-eluting stents may be associated with an increased mortality. The effect of drug-eluting stents on mortality in African-Americans is unknown. We evaluated 628 African-American patients (354 patients treated with drug-eluting stents and 274 patients treated with bare metal stents) between January 2003 and August 2005, using data from our bolus-only platelet glycoprotein IIb/IIIa inhibitor database. The primary end point was all-cause mortality obtained using social security death index. After a mean follow-up of 3+/-0.9 years, the mortality rate in the bare metal stents group was 12.8% compared with 7.1% in the drug-eluting stents group [adjusted P value=0.19; hazard ratio (HR) for bare metal stents group compared with drug-eluting stents group for death=1.4; 95% confidence interval (CI): 0.8-2.4]. In a subgroup analysis, patients presenting with acute coronary syndrome had a higher mortality when treated with bare metal stents compared with drug-eluting stents (17.1 vs. 6.3%, P=0.022; HR=2.2; 95% CI: 1.1-4.4). Patients with chronic kidney disease (all patients with creatinine >1.5 mg/dl) also had a higher mortality with bare metal stents compared with drug-eluting stents (36.7 vs. 20.4%, P=0.044; HR=2.3; 95% CI: 1.02-5.2). Drug-eluting stents seem to be safe in African-Americans and may improve survival in certain subgroups such as patients with acute coronary syndromes and chronic kidney disease.

  1. Everolimus Initiation With Early Calcineurin Inhibitor Withdrawal in De Novo Heart Transplant Recipients

    DEFF Research Database (Denmark)

    Andreassen, A K; Andersson, B; Gustafsson, F

    2016-01-01

    In a randomized, open-label trial, de novo heart transplant recipients were randomized to everolimus (3-6 ng/mL) with reduced-exposure calcineurin inhibitor (CNI; cyclosporine) to weeks 7-11 after transplant, followed by increased everolimus exposure (target 6-10 ng/mL) with cyclosporine withdrawal...... events occurred in 37.3% and 19.6% of everolimus- and CNI-treated patients, respectively (p = 0.078). These results suggest that early CNI withdrawal after heart transplantation supported by everolimus, mycophenolic acid and steroids with lymphocyte-depleting induction is safe at intermediate follow...

  2. Woven Coronary Artery Disease Successfully Managed with Percutaneous Coronary Intervention: A New Case Report

    Directory of Open Access Journals (Sweden)

    Yakup Alsancak

    2015-01-01

    Full Text Available Woven coronary artery is relatively rare and can be complicated in both acute and chronic phases. A few case reports have been published until now. Herein we report a case with right woven coronary artery managed with drug-eluted stent implantation without complication.

  3. Long-term efficacy and safety of biodegradable-polymer biolimus-eluting stents: main results of the Basel Stent Kosten-Effektivitäts Trial-PROspective Validation Examination II (BASKET-PROVE II), a randomized, controlled noninferiority 2-year outcome trial.

    Science.gov (United States)

    Kaiser, Christoph; Galatius, Soeren; Jeger, Raban; Gilgen, Nicole; Skov Jensen, Jan; Naber, Christoph; Alber, Hannes; Wanitschek, Maria; Eberli, Franz; Kurz, David J; Pedrazzini, Giovanni; Moccetti, Tiziano; Rickli, Hans; Weilenmann, Daniel; Vuillomenet, André; Steiner, Martin; Von Felten, Stefanie; Vogt, Deborah R; Wadt Hansen, Kim; Rickenbacher, Peter; Conen, David; Müller, Christian; Buser, Peter; Hoffmann, Andreas; Pfisterer, Matthias

    2015-01-06

    Biodegradable-polymer drug-eluting stents (BP-DES) were developed to be as effective as second-generation durable-polymer drug-eluting stents (DP-DES) and as safe >1 year as bare-metal stents (BMS). Thus, very late stent thrombosis (VLST) attributable to durable polymers should no longer appear. To address these early and late aspects, 2291 patients presenting with acute or stable coronary disease needing stents ≥3.0 mm in diameter between April 2010 and May 2012 were randomly assigned to biolimus-A9-eluting BP-DES, second-generation everolimus-eluting DP-DES, or thin-strut silicon-carbide-coated BMS in 8 European centers. All patients were treated with aspirin and risk-adjusted doses of prasugrel. The primary end point was combined cardiac death, myocardial infarction, and clinically indicated target-vessel revascularization within 2 years. The combined secondary safety end point was a composite of VLST, myocardial infarction, and cardiac death. The cumulative incidence of the primary end point was 7.6% with BP-DES, 6.8% with DP-DES, and 12.7% with BMS. By intention-to-treat BP-DES were noninferior (predefined margin, 3.80%) compared with DP-DES (absolute risk difference, 0.78%; -1.93% to 3.50%; P for noninferiority 0.042; per protocol P=0.09) and superior to BMS (absolute risk difference, -5.16; -8.32 to -2.01; P=0.0011). The 3 stent groups did not differ in the combined safety end point, with no decrease in events >1 year, particularly VLST with BP-DES. In large vessel stenting, BP-DES appeared barely noninferior compared with DP-DES and more effective than thin-strut BMS, but without evidence for better safety nor lower VLST rates >1 year. Findings challenge the concept that durable polymers are key in VLST formation. http://www.clinicaltrials.gov. Unique identifier: NCT01166685. © 2014 American Heart Association, Inc.

  4. Effect of biolimus-eluting stents with biodegradable polymer vs bare-metal stents on cardiovascular events among patients with acute myocardial infarction

    DEFF Research Database (Denmark)

    Räber, Lorenz; Kelbæk, Henning; Ostojic, Miodrag

    2012-01-01

    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).......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)....

  5. Long-term outcome after drug-eluting versus bare-metal stent implantation in patients with ST-segment elevation myocardial infarction

    DEFF Research Database (Denmark)

    Holmvang, Lene; Kelbæk, Henning; Kaltoft, Anne Kjer

    2013-01-01

    This study sought to compare the long-term effects of drug-eluting stent (DES) compared with bare-metal stent (BMS) implantation in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention.......This study sought to compare the long-term effects of drug-eluting stent (DES) compared with bare-metal stent (BMS) implantation in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention....

  6. Drug-eluting stents: from bench-top to clinical research

    NARCIS (Netherlands)

    Basalus, Mounir Welson Zakhary

    2013-01-01

    The development of drug-eluting stents (DES) has improved the invasive treatment of obstructive coronary artery disease by reducing both, restenosis rate and need for reinterventions. This success resulted in a widespread utilization of DES in clinical practice and entailed many clinical research

  7. Impaired health status in Type D patients following PCI in the drug-eluting stent era

    DEFF Research Database (Denmark)

    Pedersen, Susanne S.; Denollet, Johan; Ong, Andrew T L

    2007-01-01

    Drug-eluting stenting reduces restenosis post-percutaneous coronary intervention (PCI), but subgroups of patients may not benefit optimally from this procedure. We examined the impact of Type D personality on health status over time and the clinical relevance of Type D as a predictor of impaired...... health status at 12 months in unselected post-PCI patients....

  8. Percutaneous coronary intervention with ABSORB biodegradable vascular scaffold in patients with left anterior descending artery disease

    Directory of Open Access Journals (Sweden)

    К. М. Ваккосов

    2017-04-01

    Full Text Available Aim. The article evaluates 30-day results of percutaneous coronary intervention (PCI with ABSORB biodegradable vascular scaffold (BVS implanted in the case of stenosis of the left anterior descending (LAD coronary artery in patients with stable angina.Methods. 64 patients with significant (≥ 70% LAD disease were included in the study. At 30 days, scaffold thrombosis and major adverse cardiovascular events (all-cause mortality, myocardial infarction, stroke, target vessel revascularization were evaluated. The indicator of successful percutaneous coronary intervention (residual stenosis ≤20% in the presence of counterpulsation corresponding to TIMI 3rd Grade and in the absence of significant in-patient clinical complications and successful intervention assessed by clinical criteria (successful percutaneous coronary intervention alongside with a decrease in objective and subjective symptoms of myocardial ischemia, or their complete disappearance were also analyzed. Results. Mean age of patients was 61.6±8.5 years, with males accounting for 64%; 33% had earlier MI, 14% – diabetes mellitus. Mean left ventricular ejection fraction was 61.3±6.8%. Left anterior descending artery disease was presented in 89% of patients with SYNTAX Score 6.6±2.2. Mean number of implanted stents was 1.2±0.4, with mean length of the stented segment equal to18.7±1.8 mm and mean diameter 3.2±0.3 mm. At 30-day follow-up, the success of intervention assessed by clinical criteria amounted to 96.9% (n=62; that of myocardial infarction 3.1% (n=2; stent thrombosis 1.56% (n=1; repeated revascularization 1.56% (n=1; major adverse cardiovascular events (MACE 3.1%.Conclusion. The implantation of everolimus-eluting BVS for LAD stenosis demonstrates satisfactory results at 30-day follow-up.Received 16 January 2017. Accepted 21 March 2017.Financing: The study did not have sponsorship.Conflict of interest: The authors declare no conflict of interest.

  9. 生物可吸收支架与药物洗脱支架治疗冠心病Meta分析%Biore sorbable stents and drug-eluting stents in treatment of coronary heart disease:a meta-analysis

    Institute of Scientific and Technical Information of China (English)

    朱永翔; 蔡金赞; 朱灏; 庞思; 何光朝; 张瑶俊

    2017-01-01

    Objective To system evaluate the safety and efficacy of absorb bioresorbable vascular scaffold (BVS) and drug-eluting stents(DES) for coronary heart disease.Methods Using computer to retrieve PubMed,EMBASE,the Cochrane Library,EBSCO,Scopus and CBMdisc;at the same time,manually retrieved relevant cardiovascular meeting records internal and international,clinical studys which had 2 years of follow-up results about Absorb BVS and new generation DES for treatment of coronary heart disease(CHD) from January 2010 to April 2017 were selected.Using RevMan 5.3 software to perform meta analysis,to compare the safety and efficacy of Absorb BVS and new generation DES for CHD.Results There were finally 9 clinical studies been selected,including 7 randomized control trials with 6 673 patients(3 766 in Absorb BVS group and 2 907 in DES group).There was no statistically significant difference between the two groups in all-cause death,cardiac death and the incidence of patient-oriented composite endpoints(P>0.05).In Absorb BVS group,the incidence of primary clinical endpoints target lesion failure rate(OR=1.38,95%CI:1.14~1.67,P0.05);Absorb BVS组患者主要临床终点靶病变失败[比值比(OR)=1.38,95%可信区间(95%CI)为1.14~1.67,P<0.05]发生率显著高于DES组;Absorb BVS组患者次要临床终点所有心肌梗死(OR=1.63,95%CI为1.27~2.08,P<0.05),明确/极可能的支架内血栓(OR=3.06,95%CI为1.96~4.78,P<0.05),极晚期支架内血栓(OR=4.36,95%CI为1.72~11.07,P<0.05),靶病变再次血运重建(OR=1.41,95%CI为1.11~1.79,P<0.05)发生率显著高于DES组.结论 Absorb BVS治疗冠心病的长期安全性与有效性可能劣于新一代DES.

  10. A Semi-Physiological Population Model to Quantify the Effect of Hematocrit on Everolimus Pharmacokinetics and Pharmacodynamics in Cancer Patients

    NARCIS (Netherlands)

    Erp, N.P. van; Herpen, C.M. van; Wit, D. de; Willemsen, A.; Burger, D.M.; Huitema, A.D.; Kapiteijn, E.; Heine, R. ter

    2016-01-01

    INTRODUCTION AND OBJECTIVE: Everolimus (a drug from the class of mammalian target of rapamycin [mTOR] inhibitors) is associated with frequent toxicity-related dose reductions. Everolimus accumulates in erythrocytes, but the extent to which hematocrit affects everolimus plasma pharmacokinetics and

  11. [Developments in percutaneous coronary intervention and coronary stents].

    Science.gov (United States)

    Simsek, C; Daemen, J; Zijlstra, F

    2014-01-01

    In The Netherlands, more than 30.000 patients undergo a percutaneous coronary intervention every year, during which a coronary stent implantation will be performed in 90% of the cases. It is estimated that more than 5 million coronary stent implantations will be performed worldwide this year. While these numbers are impressive, however, coronary stents still have as a limitation the possibility of stent thrombosis. This has been and is an important stimulus for the development of both coronary stents, from a bare metal stent via a drug eluting stent to the present-day development of bio-absorbable stents, and anti-platelet drugs,from acenocoumarol to thieropyridines. The possibility of shortening the period of use of this powerful medication by developing new kinds of non-thrombogenic stents would, for example, make it possible to achieve significant reductions in subsequent bleeding during (dental) procedures.

  12. Functional Nanoarchitectures For Enhanced Drug Eluting Stents

    Science.gov (United States)

    Saleh, Yomna E.; Gepreel, Mohamed A.; Allam, Nageh K.

    2017-01-01

    Different strategies have been investigated to allow for optimum duration and conditions for endothelium healing through the enhancement of coronary stents. In this study, a nanoarchitectured system is proposed as a surface modification for drug eluting stents. Highly oriented nanotubes were vertically grown on the surface of a new Ni-free biocompatible Ti-based alloy, as a potential material for self-expandable stents. The fabricated nanotubes were self-grown from the potential stent substrate, which are also proposed to enhance endothelial proliferation while acting as drug reservoir to hinder Vascular Smooth Muscle Cells (VSMC) proliferation. Two morphologies were synthesized to investigate the effect of structure homogeneity on the intended application. The material was characterized by field-emission scanning electron microscope (FESEM), X-ray diffraction (XRD), Raman spectroscopy, energy dispersive X-ray spectroscopy (EDX), and X-ray photoelectron spectroscopy (XPS). Nanoindentation technique was used to study the mechanical properties of the fabricated material. Cytotoxicity and proliferation studies were performed and compared for the two fabricated nanoarchitectures, versus smooth untextured samples, using in-vitro cultured endothelial cells. Finally, the drug loading capacity was experimentally studied and further supported by computational modeling of the release profile.

  13. Everolimus for Primary Intestinal Lymphangiectasia With Protein-Losing Enteropathy.

    Science.gov (United States)

    Ozeki, Michio; Hori, Tomohiro; Kanda, Kaori; Kawamoto, Norio; Ibuka, Takashi; Miyazaki, Tatsuhiko; Fukao, Toshiyuki

    2016-03-01

    Primary intestinal lymphangiectasia (PIL), also known as Waldmann's disease, is an exudative enteropathy resulting from morphologic abnormalities in the intestinal lymphatics. In this article, we describe a 12-year-old boy with PIL that led to protein-losing enteropathy characterized by diarrhea, hypoalbuminemia associated with edema (serum albumin level: 1.0 g/dL), and hypogammaglobulinemia (serum IgG level: 144 mg/dL). Severe hypoalbuminemia, electrolyte abnormalities, and tetany persisted despite a low-fat diet and propranolol. Everolimus (1.6 mg/m(2)/day) was added to his treatment as an antiangiogenic agent. With everolimus treatment, the patient's diarrhea resolved and replacement therapy for hypoproteinemia was less frequent. Hematologic and scintigraphy findings also improved (serum albumin level: 2.5 g/dL). There were no adverse reactions during the 12-month follow-up. To the best of our knowledge, this is the first report of everolimus use in a patient with PIL. Copyright © 2016 by the American Academy of Pediatrics.

  14. Incidence and predictors of target lesion failure in a multiethnic Asian population receiving the SYNERGY coronary stent: A prospective all-comers registry.

    Science.gov (United States)

    Ananthakrishna, Rajiv; Kristanto, William; Liu, Li; Chan, Siew-Pang; Loh, Poay Huan; Tay, Edgar L; Chan, Koo Hui; Chan, Mark Y; Lee, Chi-Hang; Low, Adrian F; Tan, Huay Cheem; Loh, Joshua P

    2018-03-07

    To evaluate the target lesion failure (TLF) rate of the SYNERGY stent in all-comers, multiethnic Asian population. Currently, most drug eluting stents deliver anti-proliferative drugs from a durable polymer which is associated with a risk of late stent thrombosis. The novel everolimus-eluting, platinum chromium SYNERGY stent is coated with a bioabsorbable abluminal polymer that resolves within 4 months. This was a prospective, single center registry of consecutive patients treated with the SYNERGY stent between December 2012 and April 2015. The primary outcome was the incidence of TLF, defined as the combination of cardiac death, target vessel myocardial infarction, or clinically driven target lesion revascularization (TLR) at 1 year. A total of 807 patients received the SYNERGY stent during the study period. One-year clinical outcome data was available for 765 patients (94.8%) and were considered for statistical analysis. The mean age was 60.7 ± 10.8 years, and 83.4% were males. Patients with acute myocardial infarction consisted of 50.3% (ST-segment elevation myocardial infarction: 23.0%, Non-ST-segment elevation myocardial infarction: 27.3%) of the study population. The treated lesions were complex (ACC/AHA type B2/C: 72.7%). The primary end point of TLF at 1 year was 5.8%. Rates of cardiac mortality, target vessel myocardial infarction, and TLR were 4.2, 1.0, and 1.3%, respectively, at 1 year. Predictors of the incidence and time to early TLF were female gender, Malay ethnicity, diabetes mellitus, acute myocardial infarction at presentation, a prior history of coronary artery bypass surgery and the presence of lesion calcification. The incidence of definite stent thrombosis was 0.4% at 1 year. In this registry, the use of the SYNERGY stent was associated with low rates of TLF at 1 year. © 2018 Wiley Periodicals, Inc.

  15. A phase Ib study of everolimus combined with metformin for patients with advanced cancer.

    Science.gov (United States)

    Molenaar, Remco J; van de Venne, Tim; Weterman, Mariëtte J; Mathot, Ron A; Klümpen, Heinz-Josef; Richel, Dick J; Wilmink, Johanna W

    2018-02-01

    Background The efficacy to monotherapy with the mTOR inhibitor everolimus in advanced cancer is often limited due to therapy resistance. Combining everolimus with metformin may decrease the chance of therapy resistance. Methods Patients received everolimus and metformin in a 3 + 3 dose-escalation scheme. Objectives were to determine the dose-limiting toxicities (DLTs), maximum tolerated dose, toxic effects, pharmacokinetics and anti-tumour efficacy. Results 9 patients received study treatment for a median duration of 48 days (range: 4-78). 6 patients discontinued due to toxicity and 3 patients because of progressive disease. At the starting dose level of 10 mg everolimus qd and 500 mg metformin bid, 3 out of 5 patients experienced a DLT. After de-escalation to 5 mg everolimus qd and 500 mg metformin bid, considerable toxicity was still observed and patient enrollment was terminated. In pharmacokinetic analyses, metformin was eliminated slower when co-administered with everolimus than as single-agent. After 9 weeks of treatment, 3 patients were still on study and all had stable disease. Conclusion The combination of everolimus and metformin is poorly tolerated in patients with advanced cancer. The pharmacokinetic interaction between everolimus and metformin may have implications for diabetic cancer patients that are treated with these drugs. Our results advocate for future clinical trials with combinations of other mTOR inhibitors and biguanides.

  16. Everolimus-induced pneumonitis associates with favourable outcome in patients with metastatic renal cell carcinoma

    DEFF Research Database (Denmark)

    Penttilä, P; Donskov, F; Rautiola, J

    2017-01-01

    BACKGROUND: Mammalian target of rapamycin inhibitors may induce pneumonitis. We analysed the association of pneumonitis with outcomes in everolimus treated metastatic renal cell carcinoma (mRCC) patients. PATIENTS AND METHODS: Eighty-five mRCC patients received everolimus at Helsinki University...

  17. Optimizing everolimus exposure when combined with calcineurin inhibitors in solid organ transplantation

    NARCIS (Netherlands)

    T. van Gelder (Teun); L. Fischer (Lutz); Shihab, F. (Fuad); M. Shipkova (Maria)

    2017-01-01

    textabstractThe mammalian target of rapamycin (mTOR) inhibitor everolimus is a narrow therapeutic index drug for which optimal exposure levels are essential. The consistent pharmacokinetic profile of everolimus allows trough concentration (C0) measurement to be an appropriate and reliable index for

  18. Everolimus with reduced calcineurin inhibitor in thoracic transplant recipients with renal dysfunction: a multicenter, randomized trial

    DEFF Research Database (Denmark)

    Gullestad, Lars; Iversen, Martin; Mortensen, Svend-Aage

    2010-01-01

    The proliferation signal inhibitor everolimus offers the potential to reduce calcineurin inhibitor (CNI) exposure and alleviate CNI-related nephrotoxicity. Randomized trials in maintenance thoracic transplant patients are lacking.......The proliferation signal inhibitor everolimus offers the potential to reduce calcineurin inhibitor (CNI) exposure and alleviate CNI-related nephrotoxicity. Randomized trials in maintenance thoracic transplant patients are lacking....

  19. The Indicating FTA Elute Cartridge

    Science.gov (United States)

    de Bie, Roosmarie P.; Schmeink, Channa E.; Bakkers, Judith M.J.E.; Snijders, Peter J.F.; Quint, Wim G.V.; Massuger, Leon F.A.G.; Bekkers, Ruud L.M.; Melchers, Willem J.G.

    2011-01-01

    The clinically validated high-risk human papillomavirus (hrHPV) Hybrid Capture 2 (HC2) and GP5+/6+-PCR assays were analyzed on an Indicating FTA Elute cartridge (FTA cartridge). The FTA cartridge is a solid dry carrier that allows safe transport of cervical samples. FTA cartridge samples were compared with liquid-based samples for hrHPV and high-grade cervical intraepithelial neoplasia (CIN) detection. One cervical sample was collected in a liquid-based medium, and one was applied to the FTA cartridge. DNA was eluted directly from the FTA cartridge by a simple elution step. HC2 and GP5+/6+-PCR assays were performed on both the liquid-based and the FTA-eluted DNA of 88 women. Overall agreement between FTA and liquid-based samples for the presence of hrHPV was 90.9% with GP5+/6+-PCR and 77.3% with HC2. The sensitivity for high-grade CIN of hrHPV testing on the FTA cartridges was 84.6% with GP5+/6+-PCR and only 53.8% with HC2. By comparison, these sensitivities on liquid-based samples were 92.3% and 100% for GP5+/6+-PCR and HC2, respectively. Therefore, the FTA cartridge shows reasonably good overall agreement for hrHPV detection with liquid-based media when using GP5+/6+-PCR but not HC2 testing. Even with GP5+/6+-PCR, the FTA cartridge is not yet capable of detecting all high-grade CIN lesions. PMID:21704269

  20. Amenorrhea as a rare drug-related adverse event associated with everolimus for pancreatic neuroendocrine tumors.

    Science.gov (United States)

    Kawaguchi, Yoshiaki; Maruno, Atsuko; Kawashima, Yohei; Ito, Hiroyuki; Ogawa, Masami; Mine, Tetsuya

    2014-11-14

    The patient was an asymptomatic 43-year-old woman. Abdominal ultrasonography and enhanced computed tomography showed a tumor lesion accompanied by multiple cystic changes in the liver and the pancreatic tail. Endoscopic ultrasound-fine needle aspiration was performed on the pancreatic tumor lesion and revealed pancreatic neuroendocrine tumor (PNET). As it was unresectable due to multiple liver metastases, the decision was made to initiate treatment with everolimus and transcatheter arterial chemoembolization. The patient ceased menstruating after the start of everolimus administration. When the administration was discontinued due to interstitial lung disease, menstruation resumed, but then again stopped with everolimus resumption. An association between everolimus and amenorrhea was highly suspected. Amenorrhea occurred as a rare adverse event of everolimus. As the younger women might be included in PNETs patients, we should put this adverse event into consideration.

  1. Negative and positive affect are independently associated with patient-reported health status following percutaneous coronary intervention

    DEFF Research Database (Denmark)

    Versteeg, Henneke; Pedersen, Susanne S.; Erdman, Ruud A M

    2009-01-01

    We examined the association between negative and positive affect and 12-month health status in patients treated with percutaneous coronary intervention (PCI) with drug-eluting stents.......We examined the association between negative and positive affect and 12-month health status in patients treated with percutaneous coronary intervention (PCI) with drug-eluting stents....

  2. Advantages and disadvantages of biodegradable platforms in drug eluting stents.

    Science.gov (United States)

    Rodriguez-Granillo, Agustina; Rubilar, Bibiana; Rodriguez-Granillo, Gaston; Rodriguez, Alfredo E

    2011-03-26

    Coronary angioplasty with drug-eluting stent (DES) implantation is currently the most common stent procedure worldwide. Since the introduction of DES, coronary restenosis as well as the incidence of target vessel and target lesion revascularization have been significantly reduced. However, the incidence of very late stent thrombosis beyond the first year after stent deployment has more commonly been linked to DES than to bare-metal stent (BMS) implantation. Several factors have been associated with very late stent thrombosis after DES implantation, such as delayed healing, inflammation, stent mal-apposition and endothelial dysfunction. Some of these adverse events were associated with the presence of durable polymers, which were essential to allow the elution of the immunosuppressive drug in the first DES designs. The introduction of erodable polymers in DES technology has provided the potential to complete the degradation of the polymer simultaneously or immediately after the release of the immunosuppressive drug, after which a BMS remains in place. Several DES designs with biodegradable (BIO) polymers have been introduced in preclinical and clinical studies, including randomized trials. In this review, we analyze the clinical results from 6 observational and randomized studies with BIO polymers and discuss advantages and disadvantages of this new technology.

  3. Impact of polymer formulations on neointimal proliferation after zotarolimus-eluting stent with different polymers: insights from the RESOLUTE trial.

    Science.gov (United States)

    Waseda, Katsuhisa; Ako, Junya; Yamasaki, Masao; Koizumi, Tomomi; Sakurai, Ryota; Hongo, Yoichiro; Koo, Bon-Kwon; Ormiston, John; Worthley, Stephen G; Whitbourn, Robert J; Walters, Darren L; Meredith, Ian T; Fitzgerald, Peter J; Honda, Yasuhiro

    2011-06-01

    Polymer formulation may affect the efficacy of drug-eluting stents. Resolute, Endeavor, and ZoMaxx are zotarolimus-eluting stents with different stent platforms and different polymer coatings and have been tested in clinical trials. The aim of this analysis was to compare the efficacy of zotarolimus-eluting stents with different polymers. Data were obtained from the first-in man trial or first randomized trials of each stent, The Clinical RESpOnse EvaLUation of the MedTronic Endeavor CR ABT-578 Eluting Coronary Stent System in De Novo Native Coronary Artery Lesions (RESOLUTE), Randomized Controlled Trial to Evaluate the Safety and Efficacy of the Medtronic AVE ABT-578 Eluting Driver Coronary Stent in De Novo Native Coronary Artery Lesions (ENDEAVOR II), and ZoMaxx I trials. Follow-up intravascular ultrasound analyses (8 to 9 months of follow-up) were possible in 353 patients (Resolute: 88, Endeavor: 98, ZoMaxx: 82, Driver: 85). Volume index (volume/stent length) was obtained for vessel, stent, lumen, peristent plaque, and neointima. Cross-sectional narrowing was defined as neointimal area divided by stent area (%). Neointima-free frame ratio was calculated as the number of frames without intravascular ultrasound-detectable neointima divided by the total number of frames within the stent. At baseline, vessel, lumen, and peristent plaque volume index were not significantly different among the 4 stent groups. At follow-up, percent neointimal obstruction was significantly lower in Resolute compared with Endeavor, ZoMaxx, and Driver (Resolute: 3.7±4.0, Endeavor: 17.5±10.1, ZoMaxx: 14.6±8.1, Driver: 29.4±17.2%; Ppolymer used in Resolute independently correlated with neointimal suppression among 3 zotarolimus-eluting stents. The different polymer formulations significantly affect the relative amount of neointima for zotarolimus-eluting stents. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00248079.

  4. Glycolysis in Panc-1 human pancreatic cancer cells is inhibited by everolimus.

    Science.gov (United States)

    Liu, Ling; Gong, Liansheng; Zhang, Yangde; Li, Nianfeng

    2013-01-01

    The aim of this study was to evaluate the effects and molecular mechanisms of everolimus on Panc-1 human pancreatic cancer cells. Panc-1 human pancreatic cancer cells were treated with everolimus (10 μg/ml) at selected time points (6, 12 and 24 h). Cell proliferation and apoptosis were evaluated by MTT and flow cytometric analyses. The glycolytic activity was determined by measuring the activity of the key enzyme lactate dehydrogenase (LDH) and lactate production. The activity of mammalian target of rapamycin (mTOR) signaling was measured by western blotting. The expression of genes, including hexokinase 2 (HK2) and microRNA-143 (miR-143), was evaluated by real-time polymerase chain reaction (PCR). The administration of everolimus time-dependently inhibited proliferation and glycolysis and induced apoptosis in the Panc-1 human pancreatic cancer cells. As the time of treatment with everolimus increased, the mTOR signaling activity decreased, indicated by lower phosphorylation levels of S6 kinase; however, the phosphorylation levels of mTOR barely changed. Moreover, our data showed an everolimus-induced increase in miR-143 and decrease in HK2 in Panc-1 cells in a time-dependent manner. In conclusion, the current study indicates a novel role of everolimus in its antitumor effect as an inhibitor of glycolysis in Panc-1 human pancreatic cancer cells. Furthermore, our data highlights the significance of exploring the mechanisms of everolimus and miR-143 in malignant tumors.

  5. Role of everolimus in the treatment of renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Saby George

    2009-08-01

    Full Text Available Saby George1, Ronald M Bukowski21University of Texas Health Sciences Center, MC-8221, Division of Hematology and Oncology, San Antonio, Texas, USA; 2CCF Lerner College of Medicine Division of Hematology and Oncology, Cleveland, Ohio, USAAbstract: The therapeutic options in metastatic renal cell carcinoma have been recently expanded by the discovery of the VHL gene, the mutation of which is associated with development of clear cell carcinoma, and overexpression of the angiogenesis pathway, resulting in a very vascular tumor. This breakthrough in science led to the development of a variety of small molecules inhibiting the VEGF-dependent angiogenic pathway, such as sunitinib and sorafenib. These agents prolong overall and progression-free survival, respectively. The result was the development of robust front-line therapies which ultimately fail and are associated with disease progression. In this setting, there existed an unmet need for developing second-line therapies for patients with refractory metastatic renal cell carcinoma (MRCC. Everolimus (RAD 001 is an oral inhibitor of the mammalian target of rapamycin (mTOR pathway. The double-blind, randomized, placebo-controlled phase III trial of everolimus (RECORD-1 conducted in MRCC patients after progression on sunitinib or sorafenib, or both, demonstrated a progression-free survival benefit favoring the study drug (4.9 months vs 1.9 months, HR 0.33, 95% CI 0.25 to 0.43, P ≤ 0 0.001. Everolimus thus established itself as a standard of care in the second-line setting for patients with MRCC who have failed treatment with VEGF receptor inhibitors.Keywords: mTOR inhibitor, mammalian target of rapamycin inhibitor, signal transduction inhibitor, renal cell carcinoma, targeted therapy

  6. Recommendations for use of everolimus after heart transplantation: results from a Latin-American Consensus Meeting.

    Science.gov (United States)

    Bocchi, E A; Ahualli, L; Amuchastegui, M; Boullon, F; Cerutti, B; Colque, R; Fernandez, D; Fiorelli, A; Olaya, P; Vulcado, N; Perrone, S V

    2006-04-01

    Despite improvements during the last decades, heart transplantation remains associated with several medical complications, which limit clinical outcomes: acute rejection with hemodynamic compromise, cytomegalovirus (CMV) infections, allograft vasculopathy, chronic renal failure, and neoplasias. Everolimus, a proliferation signal inhibitor, represents a new option for adjunctive immunosuppressive therapy. Everolimus displays better efficacy in de novo heart transplant patients than azathioprine for prophylaxis of biopsy-proven acute rejection episodes of at least ISHLT grade 3A (P Latin America produced recommendations for everolimus use in daily practice based on available data and their own experience.

  7. Successful drug-eluting stent implantation in a male patient with dextrocardia: a case report

    Directory of Open Access Journals (Sweden)

    Long Wenjie

    2017-12-01

    Full Text Available Situs inversus with dextrocardia is a rare condition, with complete transposition of all the body organs, including the heart. Percutaneous coronary intervention (PCI in these patients is technically difficult because of the mirror image of organs. Here, we describe a 56-year-old man with coronary heart disease with known situs inversus with dextrocardia and coronary percutaneous intervention was performed for stenosis in the right coronary artery. A drug eluting stent was implanted at this site successfully. This case suggested that the interventional management of such patients follows the same general rules as for non-dextrocardia patients, but the manipulation of the catheter and projection position choices need to be taken into consideration to obtain optimal benefits for the patient.

  8. Progress in the study of drug-eluting intra-stent thrombosis

    International Nuclear Information System (INIS)

    Guo Zhifu; Zheng Xing; Qin Yongwen

    2007-01-01

    Durg-eluting stent has been regarded as the milestone in the history of PCI for their efficiency in the prevention of coronary arterial restenosis after percutaneous coronary intervention. But unfortunately intra-stent thrombosis continues to be a serious complication of contemporary DES use. The incidence of drug-eluting stents thrombosis is at least not lower than that of bare metal stents at present. The clinical consequences of stent thrombosis are frequently catastrophic, including death in 40% to 50% of the cases or major myocardial infarction in 60% to 70%. Premature discontinuation of standard antiplatelet therapy is by far the most important predictor of stent thrombosis with DES and other predictors included renal failure, diabetes, bifurcation lesions, multiple lesions or multivessel disease, long stents, female, advanced age, stent underexpansion and residual stenosis etc. The delayed endothelialization may be the underling mechanism of DES thrombosis. (authors)

  9. Paclitaxel-eluting versus sirolimus-eluting stents in diabetes mellitus: a report from the National Heart, Lung, and Blood Institute Dynamic Registry.

    Science.gov (United States)

    Wolf, William M; Vlachos, Helen A; Marroquin, Oscar C; Lee, Joon S; Smith, Conrad; Anderson, William D; Schindler, John T; Holper, Elizabeth M; Abbott, J Dawn; Williams, David O; Laskey, Warren K; Kip, Kevin E; Kelsey, Sheryl F; Mulukutla, Suresh R

    2010-02-01

    Diabetes is a powerful predictor of adverse events in patients undergoing percutaneous coronary intervention. Drug-eluting stents reduce restenosis rates compared with bare metal stents; however, controversy remains regarding which drug-eluting stents provides greater benefit in patients with diabetes. Accordingly, we compared the safety and efficacy of sirolimus-eluting stents (SES) with paclitaxel-eluting stents (PES) among diabetic patients in a contemporary registry. Using the National Heart, Lung, and Blood Institute Dynamic Registry, we evaluated 2-year outcomes of diabetic patients undergoing percutaneous coronary interventions with SES (n=677) and PES (n=328). Clinical and demographic characteristics, including age, body mass index, insulin use, left ventricular function, and aspirin/clopidogrel use postprocedure, did not differ significantly between the groups except that PES-treated patients had a greater frequency of hypertension and hyperlipidemia. At the 2-year follow-up, no significant differences were observed between PES and SES with regard to safety or efficacy end points. PES- and SES-treated patients had similar rates of death (10.7% versus 8.2%, P=0.20), death and myocardial infarction (14.9% versus 13.6%, P=0.55), repeat revascularization (14.8% versus 17.8%, P=0.36), and stent thrombosis (1.3% versus 1.3%, P=0.95). After adjustment, no significant differences between the 2 stent types in any outcome were observed. PES and SES are equally efficacious and have similar safety profiles in diabetic patients undergoing percutaneous coronary interventions in clinical practice.

  10. Type D personality predicts death or myocardial infarction after bare metal stent or sirolimus-eluting stent implantation

    DEFF Research Database (Denmark)

    Pedersen, Susanne S.; Lemos, Pedro A; van Vooren, Priya R

    2004-01-01

    We investigated the effect of Type D personality on the occurrence of adverse events at nine months in patients with ischemic heart disease (IHD) after percutaneous coronary intervention (PCI) with sirolimus-eluting stents (SESs) or bare stents. Type D patients experience increased negative...

  11. Improved renal function after early conversion from a calcineurin inhibitor to everolimus

    DEFF Research Database (Denmark)

    Mjörnstedt, L; Sørensen, S S; von Zur Mühlen, B

    2012-01-01

    .2) mL/min with everolimus versus a decrease of 0.4 (12.0) mL/min in controls (p graft or patient survival. The 12-month incidence of biopsy-proven acute rejection (BPAR) was 27.5% (n = 28) with everolimus and 11.0% (n = 11) in controls (p = 0.004). All......In an open-label, multicenter trial, de novo kidney transplant recipients at low to medium immunological risk were randomized at week 7 posttransplant to remain on CsA (n = 100, controls) or convert to everolimus (n = 102), both with enteric-coated mycophenolate sodium and corticosteroids...... controls (3.0%; p = 0.030). In conclusion, conversion from CsA to everolimus at week 7 after kidney transplantation was associated with a greater improvement in mGFR at month 12 versus CNI-treated controls but discontinuations and BPAR were more frequent....

  12. Magmaris: a new generation metallic sirolimus-eluting fully bioresorbable scaffold: present status and future perspectives

    OpenAIRE

    Rapetto, Claudio; Leoncini, Massimo

    2017-01-01

    Drug-eluting stents (DES) have reached a high safety and efficacy profile, becoming the best option for percutaneous coronary interventions (PCI) based revascularization. However, despite their optimal performance, a few concerns remain regarding their use, mainly due to permanent caging of the vessels and its consequences, first of all late stent thrombosis (ST). Bioresorbable scaffolds (BRS) aim to overcome these issues. The results achieved in randomized controlled trials (RCT) by the firs...

  13. Elution behaviors of elements from the hair

    International Nuclear Information System (INIS)

    Akashi, Junko; Fukushima, Ichiro; Imahori, Akira

    1981-01-01

    The elution of the neutron activated elements out of hair soaked in some organic solvents and EDTA solution was studied. Soakage of the hair sample, which was washed with water and acetone in advance as IAEA's proposal, in ether and acetone for 30 minutes each resulted in no elution of Hg, Zn, Co and Se. Elution of Zn and Co from the powdered hair sample soaked in 0.1 M EDTA solution was rapid, while Zn did not elute out from the cut hair (2 -- 3 mm length) on the same condition. Hg, Se and Au were not eluted out by 0.1 M EDTA solution in the both case of cut hair and of powdered hair. Br was removed by 0.1 M EDTA solution from the cut hair and from the powdered hair with equal ease. (author)

  14. Polymorphisms associated with everolimus pharmacokinetics, toxicity and survival in metastatic breast cancer.

    Directory of Open Access Journals (Sweden)

    Tomas Pascual

    Full Text Available Metastatic breast cancer (MBC progressing after endocrine therapy frequently activates PI3K/AKT/mTOR pathway. The BOLERO-2 trial showed that everolimus-exemestane achieves increased progression free survival (PFS compared with exemestane. However, there is great inter-patient variability in toxicity and response to exemestane-everolimus treatment. The objective of this study was to perform an exploratory study analyzing the implication of single nucleotide polymorphisms (SNPs on outcomes from this treatment through a pharmacogenetic analysis.Blood was collected from 90 postmenopausal women with hormone receptor-positive, HER2-negative MBC treated with exemestane-everolimus following progression after prior treatment with a non-steroidal aromatase inhibitor. Everolimus pharmacokinetics was measured in 37 patients. Twelve SNPs in genes involved in everolimus pharmacokinetics and pharmacodynamics were genotyped and associations assessed with drug plasma levels, clinically relevant toxicities (non-infectious pneumonitis, mucositis, hyperglycemia and hematological toxicities, dose reductions or treatment suspensions due to toxicity, progression free survival (PFS and overall survival.We found that CYP3A4 rs35599367 variant (CYP3A4*22 allele carriers had higher everolimus blood concentration compared to wild type patients (P = 0.019. ABCB1 rs1045642 was associated with risk of mucositis (P = 0.031, while PIK3R1 rs10515074 and RAPTOR rs9906827 were associated with hyperglycemia and non-infectious pneumonitis (P = 0.016 and 0.024, respectively. Furthermore, RAPTOR rs9906827 was associated with PFS (P = 0.006.CYP3A4*22 allele influenced plasma concentration of everolimus and several SNPs in PI3K/AKT/mTOR pathway genes were associated with treatment toxicities and prognosis. These results require replication, but suggest that germline variation could influence everolimus outcomes in MBC.

  15. Evaluation of the Impact of the Cancer Therapy Everolimus on the Central Nervous System in Mice

    Science.gov (United States)

    Dubois, Martine; Le Joncour, Vadim; Tonon, Marie-Christine; Anouar, Youssef; Proust, François; Morin, Fabrice; Gandolfo, Pierrick; Joly, Florence; Hilber, Pascal; Castel, Hélène

    2014-01-01

    Cancer and treatments may induce cognitive impairments in cancer patients, and the causal link between chemotherapy and cognitive dysfunctions was recently validated in animal models. New cancer targeted therapies have become widely used, and their impact on brain functions and quality of life needs to be explored. We evaluated the impact of everolimus, an anticancer agent targeting the mTOR pathway, on cognitive functions, cerebral metabolism, and hippocampal cell proliferation/vascular density in mice. Adult mice received everolimus daily for 2 weeks, and behavioral tests were performed from 1 week after the last treatment. Everolimus-treated mice displayed a marked reduction in weight gain from the last day of the treatment period. Ex vivo analysis showed altered cytochrome oxidase activity in selective cerebral regions involved in energy balance, food intake, reward, learning and memory modulation, sleep/wake cycle regulation, and arousal. Like chemotherapy, everolimus did not alter emotional reactivity, learning and memory performances, but in contrast to chemotherapy, did not affect behavioral flexibility or reactivity to novelty. In vivo hippocampal neural cell proliferation and vascular density were also unchanged after everolimus treatments. In conclusion, two weeks daily everolimus treatment at the clinical dose did not evoke alteration of cognitive performances evaluated in hippocampal- and prefrontal cortex-dependent tasks that would persist at one to four weeks after the end of the treatment completion. However, acute everolimus treatment caused selective CO modifications without altering the mTOR effector P70S6 kinase in cerebral regions involved in feeding behavior and/or the sleep/wake cycle, at least in part under control of the solitary nucleus and the parasubthalamic region of the hypothalamus. Thus, this area may represent a key target for everolimus-mediating peripheral modifications, which has been previously associated with symptoms such as

  16. Evaluation of the impact of the cancer therapy everolimus on the central nervous system in mice.

    Directory of Open Access Journals (Sweden)

    Martine Dubois

    Full Text Available Cancer and treatments may induce cognitive impairments in cancer patients, and the causal link between chemotherapy and cognitive dysfunctions was recently validated in animal models. New cancer targeted therapies have become widely used, and their impact on brain functions and quality of life needs to be explored. We evaluated the impact of everolimus, an anticancer agent targeting the mTOR pathway, on cognitive functions, cerebral metabolism, and hippocampal cell proliferation/vascular density in mice. Adult mice received everolimus daily for 2 weeks, and behavioral tests were performed from 1 week after the last treatment. Everolimus-treated mice displayed a marked reduction in weight gain from the last day of the treatment period. Ex vivo analysis showed altered cytochrome oxidase activity in selective cerebral regions involved in energy balance, food intake, reward, learning and memory modulation, sleep/wake cycle regulation, and arousal. Like chemotherapy, everolimus did not alter emotional reactivity, learning and memory performances, but in contrast to chemotherapy, did not affect behavioral flexibility or reactivity to novelty. In vivo hippocampal neural cell proliferation and vascular density were also unchanged after everolimus treatments. In conclusion, two weeks daily everolimus treatment at the clinical dose did not evoke alteration of cognitive performances evaluated in hippocampal- and prefrontal cortex-dependent tasks that would persist at one to four weeks after the end of the treatment completion. However, acute everolimus treatment caused selective CO modifications without altering the mTOR effector P70S6 kinase in cerebral regions involved in feeding behavior and/or the sleep/wake cycle, at least in part under control of the solitary nucleus and the parasubthalamic region of the hypothalamus. Thus, this area may represent a key target for everolimus-mediating peripheral modifications, which has been previously associated

  17. Increased rate of stent thrombosis and target lesion revascularization after filter protection in primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: 15-month follow-up of the DEDICATION (Drug Elution and Distal Protection in ST Elevation Myocardial Infarction) trial

    DEFF Research Database (Denmark)

    Kaltoft, Anne; Kelbaek, Henning; Kløvgaard, Lene

    2010-01-01

    The purpose of this study was to evaluate the long-term effects of distal protection during percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI).......The purpose of this study was to evaluate the long-term effects of distal protection during percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI)....

  18. CheckMate 025 Randomized Phase 3 Study: Outcomes by Key Baseline Factors and Prior Therapy for Nivolumab Versus Everolimus in Advanced Renal Cell Carcinoma

    DEFF Research Database (Denmark)

    Escudier, Bernard; Sharma, Padmanee; McDermott, David F

    2017-01-01

    /kg every 2 wk or everolimus 10mg once daily. RESULTS AND LIMITATIONS: The minimum follow-up was 14 mo. Baseline subgroup distributions were balanced between nivolumab and everolimus arms. Nivolumab demonstrated an OS improvement versus everolimus across subgroups, including Memorial Sloan Kettering Cancer...... Center (MSKCC) and International Metastatic Renal Cell Carcinoma Database Consortium risk groups; age

  19. Impact of everolimus: update on immunosuppressive therapy strategies and patient outcomes after renal transplantation

    Directory of Open Access Journals (Sweden)

    Helio Tedesco-Silva Jr

    2011-01-01

    Full Text Available Helio Tedesco-Silva Jr, Claudia Rosso Felipe, Tainá Veras de Sandes Freitas, Marina Pontello Cristeli, Carolina Araújo Rodrigues, José Osmar Medina PestanaNephrology Division, Hospital do Rim e Hipertensão, Universidade Federal de São Paulo, BrazilAbstract: Everolimus is an immunosuppressive agent used for the prophylaxis of acute rejection after kidney transplantation. Everolimus inhibits the activity of the serine/threonine kinase mammalian target of rapamycin (mTOR, a key enzyme that controls cell growth and metabolism, producing cell cycle arrest from the G1 to S phase. As a consequence, everolimus has antiproliferative and antineoplastic effects. Everolimus is a drug with a narrow therapeutic index. The pharmacokinetics of everolimus indicates a need for twice-daily dosing. Intra- and interindividual variability and drug–drug interactions suggest the need for therapeutic drug monitoring to maximize the efficacy/toxicity ratio. The good correlation between exposure (area under the concentration–time curve and trough concentration indicates that monitoring of everolimus trough concentrations is an adequate strategy after kidney transplantation. Everolimus is indicated for low- to moderate-risk de novo kidney transplant candidates. There are no conclusive studies thus far indicating that everolimus can be used in high-risk patients, such as sensitized patients, retransplants, and African Americans. In de novo kidney transplant recipients, the recommended initial dose of everolimus is 0.75 mg twice daily, adjusted to maintain blood trough concentrations of 3–8 ng/mL, in combination with progressive reduction in blood trough cyclosporine concentrations to 25–50 ng/mL. In combination with reduced trough blood tacrolimus concentrations of 4–7 ng/mL the recommended initial dose of everolimus is 1.5 mg twice daily, adjusted to maintain trough blood concentrations of 3–8 ng/mL. Everolimus can also be used as a conversion strategy

  20. Updates in management of coronary artery disease

    International Nuclear Information System (INIS)

    Yang, Dong Heon; Chae, Shung Chull

    2005-01-01

    Coronary artery disease (CAD) has been increasing during the last decade and is the one of major causes of death. The management of patients with coronary artery disease has evolved considerably. There are two main strategies in the management of CAD, complementary, not competitive, each other; the pharmacologic therapy to prevent and treat CAD and the percutaneous coronary intervention (PCI) to restore coronary flow. Antiplatelet drugs and cholesterol lowering drugs have central roles in pharmacotherapy. Drug eluting stent (DES) bring about revolutional changes in PCL in the management of patients with ST segment elevation acute myocardial infarction (AMI), there has been a debate on the better strategy for the restoration of coronary flow. Thrombolytic therapy is widely available and easy to administer, whereas primary PCI is less available and more complex, but more complete. Recently published evidences in the pharmacologic therapy including antiplatelet and statin, and PCI including DES and reperfusion therapy in patients with ST segment elevation AMI were reviewed

  1. Updates in management of coronary artery disease

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Dong Heon; Chae, Shung Chull [Kyungpook National University Medical School, Daegu (Korea, Republic of)

    2005-02-15

    Coronary artery disease (CAD) has been increasing during the last decade and is the one of major causes of death. The management of patients with coronary artery disease has evolved considerably. There are two main strategies in the management of CAD, complementary, not competitive, each other; the pharmacologic therapy to prevent and treat CAD and the percutaneous coronary intervention (PCI) to restore coronary flow. Antiplatelet drugs and cholesterol lowering drugs have central roles in pharmacotherapy. Drug eluting stent (DES) bring about revolutional changes in PCL in the management of patients with ST segment elevation acute myocardial infarction (AMI), there has been a debate on the better strategy for the restoration of coronary flow. Thrombolytic therapy is widely available and easy to administer, whereas primary PCI is less available and more complex, but more complete. Recently published evidences in the pharmacologic therapy including antiplatelet and statin, and PCI including DES and reperfusion therapy in patients with ST segment elevation AMI were reviewed.

  2. Anti-tumor effects of everolimus and metformin are complementary and glucose-dependent in breast cancer cells

    NARCIS (Netherlands)

    Ariaans, Gerke; Jalving, Mathilde; de Vries, Emma Geertruida Elisabeth; de Jong, Steven

    2017-01-01

    Background: Clinical efficacy of the mTOR inhibitor everolimus is limited in breast cancer and regularly leads to side-effects including hyperglycemia. The AMPK inhibitor and anti-diabetic drug metformin may counteract everolimus-induced hyperglycemia, as well as enhancing anti-cancer efficacy. We

  3. Everolimus downregulates estrogen receptor and induces autophagy in aromatase inhibitor-resistant breast cancer cells

    International Nuclear Information System (INIS)

    Lui, Asona; New, Jacob; Ogony, Joshua; Thomas, Sufi; Lewis-Wambi, Joan

    2016-01-01

    mTOR inhibition of aromatase inhibitor (AI)-resistant breast cancer is currently under evaluation in the clinic. Everolimus/RAD001 (Afinitor®) has had limited efficacy as a solo agent but is projected to become part of combination therapy for AI-resistant breast cancer. This study was conducted to investigate the anti-proliferative and resistance mechanisms of everolimus in AI-resistant breast cancer cells. In this study we utilized two AI-resistant breast cancer cell lines, MCF-7:5C and MCF-7:2A, which were clonally derived from estrogen receptor positive (ER+) MCF-7 breast cancer cells following long-term estrogen deprivation. Cell viability assay, colony formation assay, cell cycle analysis and soft agar anchorage-independent growth assay were used to determine the efficacy of everolimus in inhibiting the proliferation and tumor forming potential of MCF-7, MCF-7:5C, MCF-7:2A and MCF10A cells. Confocal microscopy and transmission electron microscopy were used to evaluate LC3-II production and autophagosome formation, while ERE-luciferase reporter, Western blot, and RT-PCR analyses were used to assess ER expression and transcriptional activity. Everolimus inhibited the proliferation of MCF-7:5C and MCF-7:2A cells with relatively equal efficiency to parental MCF-7 breast cancer cells. The inhibitory effect of everolimus was due to G1 arrest as a result of downregulation of cyclin D1 and p21. Everolimus also dramatically reduced estrogen receptor (ER) expression (mRNA and protein) and transcriptional activity in addition to the ER chaperone, heat shock protein 90 protein (HSP90). Everolimus restored 4-hydroxy-tamoxifen (4OHT) sensitivity in MCF-7:5C cells and enhanced 4OHT sensitivity in MCF-7 and MCF-7:2A cells. Notably, we found that autophagy is one method of everolimus insensitivity in MCF-7 breast cancer cell lines. This study provides additional insight into the mechanism(s) of action of everolimus that can be used to enhance the utility of mTOR inhibitors as

  4. Effect of everolimus initiation and early calcineurin inhibitor withdrawal on myocardial FOXP3+ regulatory T cells in heart transplantation

    DEFF Research Database (Denmark)

    Mirza, Kiran; Gustafsson, Finn; Gullestad, Lars

    2016-01-01

    BACKGROUND: Through immunosuppression CD4+FoxP3+ regulatory T-cells (Tregs) play an indispensable role in allograft rejection. Post-HTx treatment with everolimus is associated with slower progression of cardiac allograft vasculopathy (CAV) - chronic rejection - than CNI based therapy. We hypothes......BACKGROUND: Through immunosuppression CD4+FoxP3+ regulatory T-cells (Tregs) play an indispensable role in allograft rejection. Post-HTx treatment with everolimus is associated with slower progression of cardiac allograft vasculopathy (CAV) - chronic rejection - than CNI based therapy. We...... hypothesized treatment with everolimus reduced the risk of CAV by modulating myocardial FoxP3 levels. METHODS: 15 patients from the Schedule trial comparing everolimus, MMF, steroid and early CNI (Everolimus, n=8) withdrawal to conventional CNI based immunosuppression (Controls, n=7) after de novo HTx were...

  5. Clinical evidence of the efficacy of everolimus and its potential in the treatment of breast cancer

    Directory of Open Access Journals (Sweden)

    Saksena R

    2013-05-01

    Full Text Available Rujuta Saksena, Serena T WongThe Cancer Institute of New Jersey, New Brunswick, NJ, USAAbstract: The PI3K/Akt/mTOR (phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin pathway regulates several key cellular functions and its dysregulation creates an environment that promotes tumorigenesis as well as resistance to therapy. The mTOR inhibitor everolimus has emerged as a promising agent in the treatment of breast cancer and was recently approved in combination with exemestane for advanced hormone receptor–positive disease after progression on a nonsteroidal aromatase inhibitor. Everolimus may also be effective in combination with cytotoxic and human epidermal growth factor receptor-2-directed therapies for the treatment of other subtypes of breast cancer. This paper highlights preclinical and clinical data that have emerged on the role of mTOR inhibition in breast cancer. Although generally well tolerated, everolimus carries a unique side effect profile of which both patients and providers should be made aware. Recommendations related to the administration of everolimus in the clinical setting are also discussed.Keywords: everolimus, breast cancer, mTOR inhibition

  6. [The drug of the month: everolimus (Afinitor) for the treatment of metastatic breast cancer].

    Science.gov (United States)

    Jerusalem, G; Rorive, A; Collignon, J

    2014-09-01

    Sequential endocrine treatments are recommended for estrogen receptor (ER) positive human epidermal growth factor receptor 2 (HER 2) negative metastatic breast cancers except in the case of symptomatic visceral disease. However, patients who suffer from disease progression while receiving a non-steroidal aromatase inhibitor (NSAI) have a very poor prognosis with standard endocrine therapy alone. Recently, based onthe results of the BOLERO 2 trial, the mammalian target of rapamycin (mTOR) inhibitor everolimus, combined with exemestane, a steroidal aromatase inhibitor, has been approved in Europe and the US for patients suffering from ER positive HER2 negative advanced breast cancer previously treated by a NSAI. The median progression-free survival (PFS) increased from 3.2 to 7.8 months in patients receiving everolimus and exemestane compared to placebo and exemestane. The magnitude of benefit was consistent in all pre-specified subgroups. Side effects were manageable and the quality of life was at least maintained. Everolimus has also beenrecently studied in HER2 positive locally advanced or metastatic disease in heavily pretreated patients (BOLERO 3 trial). This trial met its primary endpoint. The median PFS was increased in patients receiving trastuzumab, vinorelbine and everolimus compared to patients receiving trastuzumab, vinorelbine and placebo. We review pharmacological data and side effects of the drug. We also review the most important clinical trials leading to reimbursement of everolimus in metastatic breast cancer.

  7. Stent thrombosis with drug-eluting and bare-metal stents: evidence from a comprehensive network meta-analysis.

    Science.gov (United States)

    Palmerini, Tullio; Biondi-Zoccai, Giuseppe; Della Riva, Diego; Stettler, Christoph; Sangiorgi, Diego; D'Ascenzo, Fabrizio; Kimura, Takeshi; Briguori, Carlo; Sabatè, Manel; Kim, Hyo-Soo; De Waha, Antoinette; Kedhi, Elvin; Smits, Pieter C; Kaiser, Christoph; Sardella, Gennaro; Marullo, Antonino; Kirtane, Ajay J; Leon, Martin B; Stone, Gregg W

    2012-04-14

    The relative safety of drug-eluting stents and bare-metal stents, especially with respect to stent thrombosis, continues to be debated. In view of the overall low frequency of stent thrombosis, large sample sizes are needed to accurately estimate treatment differences between stents. We compared the risk of thrombosis between bare-metal and drug-eluting stents. For this network meta-analysis, randomised controlled trials comparing different drug-eluting stents or drug-eluting with bare-metal stents currently approved in the USA were identified through Medline, Embase, Cochrane databases, and proceedings of international meetings. Information about study design, inclusion and exclusion criteria, sample characteristics, and clinical outcomes was extracted. 49 trials including 50,844 patients randomly assigned to treatment groups were analysed. 1-year definite stent thrombosis was significantly lower with cobalt-chromium everolimus eluting stents (CoCr-EES) than with bare-metal stents (odds ratio [OR] 0·23, 95% CI 0·13-0·41). The significant difference in stent thrombosis between CoCr-EES and bare-metal stents was evident as early as 30 days (OR 0·21, 95% CI 0·11-0·42) and was also significant between 31 days and 1 year (OR 0·27, 95% CI 0·08-0·74). CoCr-EES were also associated with significantly lower rates of 1-year definite stent thrombosis compared with paclitaxel-eluting stents (OR 0·28, 95% CI 0·16-0·48), permanent polymer-based sirolimus-eluting stents (OR 0·41, 95% CI 0·24-0·70), phosphorylcholine-based zotarolimus-eluting stents (OR 0·21, 95% CI 0·10-0·44), and Resolute zotarolimus-eluting stents (OR 0·14, 95% CI 0·03-0·47). At 2-year follow-up, CoCr-EES were still associated with significantly lower rates of definite stent thrombosis than were bare-metal (OR 0·35, 95% CI 0·17-0·69) and paclitaxel-eluting stents (OR 0·34, 95% CI 0·19-0·62). No other drug-eluting stent had lower definite thrombosis rates compared with bare

  8. Evaluation of electrochemical ion exchange for cesium elution

    International Nuclear Information System (INIS)

    Bontha, J.D.; Kurath, D.E.; Surma, J.E.; Buehler, M.F.

    1996-04-01

    Electrochemical elution was investigated as an alternative method to acid elution for the desorption of cesium from loaded ion exchange resins. The approach was found to have several potential advantages over existing technologies, in particular, electrochemical elution eliminates the need for addition of chemicals to elute cesium from the ion exchange resin. Also, since, in the electrochemical elution process the eluting solution is not in direct contact with the ion exchange material, very small volumes of the eluting solution can be used in a complete recycle mode in order to minimize the total volume of the cesium elute. In addition, the cesium is eluted as an alkaline solution that does not require neutralization with caustic to meet the tank farm specifications. Other advantages include easy incorporation of the electrochemical elution process into the present cesium recovery schemes

  9. B-Type Natriuretic Peptide Assessment in Patients Undergoing Revascularization for Left Main Coronary Artery Disease: Analysis from the EXCEL Trial.

    Science.gov (United States)

    Redfors, Björn; Chen, Shmuel; Crowley, Aaron; Ben-Yehuda, Ori; Gersh, Bernard J; Lembo, Nicholas J; Brown, W Morris; Banning, Adrian P; Taggart, David P; Serruys, Patrick W; Kappetein, Arie Pieter; Sabik, Joseph F; Stone, Gregg W

    2018-04-17

    Background -Elevated B-type natriuretic peptide (BNP) is reflective of impaired cardiac function and is associated with worse prognosis among patients with coronary artery disease (CAD). We sought to assess the association between baseline BNP, adverse outcomes, and the relative efficacy of percutaneous coronary intervention (PCI) versus coronary artery bypass grafting (CABG) in patients with left main (LM) CAD. Methods -The EXCEL trial randomized patients with LMCAD and low or intermediate SYNTAX scores to PCI with everolimus-eluting stents versus CABG. The primary endpoint was the composite of all-cause death, myocardial infarction (MI) or stroke. We used multivariable Cox proportional hazards regression to assess the associations between normal versus elevated BNP (≥100 pg/mL), randomized treatment, and the 3-year risk of adverse events. Results -BNP at baseline was elevated in 410 of 1037 (39.5%) patients enrolled in EXCEL. Patients with elevated BNP levels were older and more frequently had additional cardiovascular risk factors and lower LVEF than those with normal BNP, but had similar SYNTAX scores. Patients with elevated BNP had significantly higher 3-year rates of the primary endpoint (18.6% vs. 11.7%, adjusted HR 1.62, 95% CI 1.16-2.28, P=0.005), and higher mortality (11.5% vs. 3.9%, adjusted HR 2.49, 95% CI 1.48-4.19, P=0.0006), both from cardiovascular and non-cardiovascular causes. In contrast, there were no significant differences in the risks of MI, stroke, ischemia-driven revascularization, stent thrombosis, graft occlusion, or major bleeding. A significant interaction (P interaction =0.03) was present between elevated versus normal BNP and treatment with PCI versus CABG for the adjusted risk of the primary composite endpoint at 3 years among patients with elevated BNP (adjusted HR for PCI versus CABG 1.54, 95% CI 0.96-2.47) versus normal BNP (adjusted HR 0.74, 95% CI 0.46-1.20). This interaction was stronger when log(BNP) was modeled as a

  10. Enhanced performance of magnesium alloy for drug-eluting vascular scaffold application

    Science.gov (United States)

    Dong, Hongzhou; Li, Daikun; Mao, Daoyong; Bai, Ningning; Chen, Yashi; Li, Qing

    2018-03-01

    Bio-absorbable magnesium alloys drug-eluting vascular scaffold was developed to resolve the defect of permanent metal and drug-eluting stents, most notably a chronic vessel wall inflammation and the risk of stent thrombosis. Nevertheless, violent chemical reaction and rapid degradation under physiological conditions limits their application. Furthermore, multifunctional drug-eluting stents which could reduce the formation of thrombus and repair the damaged vessels need more attention to fundamentally cure the coronary artery disease. Herein, a drug delivery system (Mg/MgO/PLA-FA) which can realize sustainable release of ferulaic acid was designed via anodic oxidation process and dip coating process. Electrochemical tests and immersion experiments showed that the superior anticorrosion behavior, it is due to the dense MgO-PLA composite layer. The released ferulaic acid can effectively decrease platelets adhesion and aggregation during the early stage of implantation. Besides, hemolysis tests showed that the composite coatings endowed the Mg alloy with a low hemolysis ratio. The Mg/MgO/PLA-FA composite materials may be appropriate for applications on biodegradable Mg alloys drug-eluting stents.

  11. EVALUATION OF PETROLEUM HYDROCARBONS ELUTION FROM SOIL

    Directory of Open Access Journals (Sweden)

    Janina Piekutin

    2015-06-01

    Full Text Available The paper presents studies on oil removal from soil by means of water elution with a help of shaking out the contaminants from the soil. The tests were performed on simulated soil samples contaminated with a mixture of petroleum hydrocarbons. The study consisted in recording the time influence and the number of elution cycles to remove contaminants from the soil. The samples were then subject to the determination of petroleum hydrocarbons, aliphatic hydrocarbons, and BTEX compounds (benzene, toluene, ethylbenzene, xylene. Due to adding various concentrations of petroleum into particular soil samples and applying different shaking times, it was possible to find out the impact of petroleum content and sample shaking duration on the course and possibility of petroleum substances removal by means of elution process.

  12. Everolimus in clinical practice after liver transplantation: a single-center experience

    Directory of Open Access Journals (Sweden)

    O. A. Gerasimova

    2017-01-01

    Full Text Available Aim. Single-center analysis of everolimus treatment after liver transplantation. Materials and methods. 23 patients having received Certican after OLT in RSCRST were observed in period from 6 months to 5 years; comparison group consisted of 50 patients who received immunosuppressive scheme with tacrolimus. Conversion to everolimus was performed in the period from 1 month after OLT after discharge and at later time according to the indications: hepatocellular cancer, cumulative CNI nephrotoxicity, the development of malignancies, and intolerance to CNI. The concentrations of CNI and everolimus in the blood (target concentration of tacrolimus 1.5–2 ng/ml, everolimus 3–8 ng/ml were monitored. Glomerular filtration rate (GFR was determined using the CKD-EPI equation. Adverse events of everolimus were evaluated. Results. The immunosuppressive scheme with everolimus is presented; adverse events with dose-dependent hypercholesterolemia (34.7% as the main; the average level of blood cholesterol was not significantly different from that in the control group, 5.6 ± 0.9 vs 5.1 ± 1.4 mmol/l (Z = 1.3, p = 0.17. Renal function was stable throughout the observation period (35 ± 16 months. GFR (CKD-EPI before conversion was 75.8 ± 17.5 ml/min. 6 patients treated with Certican for 5 years had final GFR 96.6 ± 5.1 ml/min. GFR in the group of Certican at 12 months post conversion was 87.5 ± 16.3 ml/min vs 94.2 ± 16.8 ml/min (p = 0.08 in the control group. We revealed metastases to the liver and lungs in 5 patients from 13 patients with HCC, survival rate in this group depended on the compliance with the Milan criteria (Z = 2.4, p = 0.02. Conclusion. Everolimus allows maintaining of a stable renal function to prevent progression of renal failure; conversion should be initiated as early as possible. Combination of everolimus with reduced dose of CNI is optimal. Despite the fact that side effects are developing in most patients, adequate monitoring of

  13. Bioresorbable Polymer Coated Metallic Stents and Fully Bioresorbable Scaffolds: Benefits and limitations in different coronary lesion subsets, -clinical and intracascular imaging results-

    NARCIS (Netherlands)

    J.M. Fam (Jiang Ming)

    2018-01-01

    markdownabstractPercutaneous coronary intervention (PCI) which involves the deployment of devices such as metallic drug eluting stents (DES) in coronary artery lesions and concomitant dual antiplatelet therapy (DAPT) is one of the mainstays of management of coronary artery disease and has become one

  14. UV-visible spectroscopy as an alternative to liquid chromatography for determination of everolimus in surfactant-containing dissolution media: a useful approach based on solid-phase extraction.

    Science.gov (United States)

    Kamberi, Marika; Tran, Thu-Ngoc

    2012-11-01

    High-throughput 96-well solid phase extraction (SPE) plate with C-18 reversed phase sorbent followed by UV-visible (UV-Vis) microplate reader was applied to the analysis of hydrophobic drugs in surfactant-containing dissolution media, which are often used to evaluate the in-vitro drug release of drug eluting stents (DES). Everolimus and dissolution medium containing Triton X-405 were selected as representatives, and the appropriate SPE conditions (adsorption, washing and elution) were investigated to obtain a practical and reliable sample clean-up. It was shown that the developed SPE procedure was capable of removing interfering components (Triton X-405 and its impurities), allowing for an accurate automated spectrophotometric analysis to be performed. The proposed UV-Vis spectrophotometric method yielded equivalent results compared to a classical LC analysis method. Linear regression analysis indicated that both methods have the ability to obtain test results that are directly proportional to the concentration of analyte in the sample within the selected range of 1.0-10 μg/ml for everolimus, with a coefficient of correlation (r(2)) value of >0.998 and standard deviation of the residuals (Syx) of UV-Vis spectrophotometric method and from 98 to 102 for the HPLC method, respectively. The 95% CI of the mean recovery for the UV-Vis spectrophotometric method was 99-102% and for the HPLC method was 99-101%. No statistical difference was found between the mean recoveries of the methods (p=0.42). Hence the methods are free from interference due to Triton and other chemicals present in the dissolution medium. The variation in the amount of everolimus estimated by UV-Vis spectrophotometric and HPLC methods was ≤3.5%, and the drug release profiles obtained by both methods were found to be equivalent by evaluation with two-one-sided t-test (two-tailed, p=0.62; mean of differences, 0.17; 95% CI, 0.62-0.96) and similarity factor f2 (f2 value, 87). The excellent conformity of

  15. Everolimus use and associated factors among post-menopausal women with hormonal receptor positive/human epidermal growth factor receptor 2 negative metastatic breast cancer.

    Science.gov (United States)

    Li, Nanxin; Hao, Yanni; Xie, Jipan; Lin, Peggy L; Zhou, Zhou; Zhong, Yichen; Signorovitch, James E; Wu, Eric Q

    2015-08-01

    Everolimus has been shown to be an effective HR+/HER2- mBC treatment in both clinical trials and real-world practice. The current study aims at understanding factors associated with everolimus use and how it is used in the real world. A retrospective chart review was conducted among postmenopausal HR+/HER2- mBC women who received everolimus, endocrine therapy (ET), or chemotherapy (CT) for mBC between 1 July 2012 and 15 April 2013 after an NSAI failure. Factors associated with everolimus use versus ET or CT were identified using multivariable logistic regressions. Reasons for prescribing everolimus and everolimus treatment patterns were described. Liver metastasis and high tumor volume were associated with a higher likelihood of everolimus use versus ET (OR = 1.67, OR = 1.62) but a lower likelihood of everolimus use versus CT (OR = 0.43, OR = 0.30). Medicare-only insurance (OR = 0.30) as well as ECOG ≥2 (OR = 3.72) and prior CT in mBC (OR = 2.76) were associated with a lower and higher likelihood of everolimus use versus CT, respectively. The top reason for prescribing everolimus was efficacy (69-85%). About 15% and 29% of everolimus users in second line and third line or above received prior CT for mBC. Exemestane was the most common concomitant therapy with everolimus (56-87%). The majority of patients initiated everolimus at the labeled dose of 10 mg daily (>80%) and maintained this dose (>80%). In the real world, everolimus was used in more severe patients than ET but less severe patients than CT based on visceral metastasis, tumor volume, and performance status. The top reason for prescribing everolimus was efficacy. A large proportion of patients received first or second line CT before everolimus initiation. The majority of patients used everolimus according to the labeled combination and dose. Future studies are needed to determine optimal sequencing of everolimus, ET, and CT for HR+/HER2- mBC.

  16. Everolimus for Advanced Pancreatic Neuroendocrine Tumours: A Subgroup Analysis Evaluating Japanese Patients in the RADIANT-3 Trial

    Science.gov (United States)

    Ito, Tetsuhide; Okusaka, Takuji; Ikeda, Masafumi; Igarashi, Hisato; Morizane, Chigusa; Nakachi, Kohei; Tajima, Takeshi; Kasuga, Akio; Fujita, Yoshie; Furuse, Junji

    2012-01-01

    Objective Everolimus, an inhibitor of the mammalian target of rapamycin, has recently demonstrated efficacy and safety in a Phase III, double-blind, randomized trial (RADIANT-3) in 410 patients with low- or intermediate-grade advanced pancreatic neuroendocrine tumours. Everolimus 10 mg/day provided a 2.4-fold improvement compared with placebo in progression-free survival, representing a 65% risk reduction for progression. The purpose of this analysis was to investigate the efficacy and safety of everolimus in the Japanese subgroup enrolled in the RADIANT-3 study. Methods Subgroup analysis of the Japanese patients was performed comparing efficacy and safety between everolimus 10 mg/day orally (n = 23) and matching placebo (n = 17). The primary endpoint was progression-free survival. Safety was evaluated on the basis of the incidence of adverse drug reactions. Results Progression-free survival was significantly prolonged with everolimus compared with placebo. The median progression-free survival was 19.45 months (95% confidence interval, 8.31–not available) with everolimus vs 2.83 months (95% confidence interval, 2.46–8.34) with placebo, resulting in an 81% risk reduction in progression (hazard ratio, 0.19; 95% confidence interval, 0.08–0.48; P< 0.001). Adverse drug reactions occurred in all 23 (100%) Japanese patients receiving everolimus and in 13 (77%) patients receiving placebo; most were grade 1/2 in severity. The most common adverse drug reactions in the everolimus group were rash (n = 20; 87%), stomatitis (n = 17; 74%), infections (n = 15; 65%), nail disorders (n = 12; 52%), epistaxis (n = 10; 44%) and pneumonitis (n = 10; 44%). Conclusions These results support the use of everolimus as a valuable treatment option for Japanese patients with advanced pancreatic neuroendocrine tumours. PMID:22859827

  17. Intravascular ultrasound assessed incomplete stent apposition and stent fracture in stent thrombosis after bare metal versus drug-eluting stent treatment the Nordic Intravascular Ultrasound Study (NIVUS)

    DEFF Research Database (Denmark)

    Kosonen, Petteri; Vikman, Saila; Jensen, Lisette Okkels

    2012-01-01

    This prospective multicenter registry used intravascular ultrasound (IVUS) in patients with definite stent thrombosis (ST) to compare rates of incomplete stent apposition (ISA), stent fracture and stent expansion in patients treated with drug-eluting (DES) versus bare metal (BMS) stents. ST...... is a rare, but potential life threatening event after coronary stent implantation. The etiology seems to be multifactorial....

  18. Softening and elution of monomers in ethanol

    DEFF Research Database (Denmark)

    Benetti, Ana Raquel; Asmussen, Erik; Munksgaard, E Christian

    2009-01-01

    The purpose of this study was to investigate the effect of light-curing protocol on softening and elution of monomers in ethanol as measured on a model polymer. It was a further aim to correlate the measured values with previously reported data on degree of conversion and glass transition...

  19. Wound complications and surgical events in de novo heart transplant patients treated with everolimus

    DEFF Research Database (Denmark)

    Rashidi, Mitra; Esmaily, Sorosh; Fiane, Arnt E

    2016-01-01

    OBJECTIVES: The use of mammalian target of rapamycin (mTOR) inhibitors have been limited by adverse events (AE), including delayed wound healing. We retrospectively reviewed all AE and serious AE (SAE) in The Scandinavian heart transplant (HTx) everolimus (EVE) de novo trial with early calcineurin...

  20. Cost utility analysis of everolimus in the treatment of metastatic renal cell cancer in the Netherlands

    NARCIS (Netherlands)

    Mihajlović, J.; Minović, I.; Bruinsma, A.; Postma, M.J.

    2013-01-01

    Objectives: Metastatic renal cell cancer (mRCC) is becoming an important part of Dutch health care expenditure due to expensive pharmaceutical options for disease control and lack of adequate prevention methods. New targeted therapeutics, such as sunitinib, sorafenib and everolimus, have recently

  1. Left main percutaneous coronary intervention.

    Science.gov (United States)

    Teirstein, Paul S; Price, Matthew J

    2012-10-23

    The introduction of drug-eluting stents and advances in catheter techniques have led to increasing acceptance of percutaneous coronary intervention (PCI) as a viable alternative to coronary artery bypass graft (CABG) for unprotected left main disease. Current guidelines state that it is reasonable to consider unprotected left main PCI in patients with low to intermediate anatomic complexity who are at increased surgical risk. Data from randomized trials involving patients who are candidates for either treatment strategy provide novel insight into the relative safety and efficacy of PCI for this lesion subset. Herein, we review the current data comparing PCI with CABG for left main disease, summarize recent guideline recommendations, and provide an update on technical considerations that may optimize clinical outcomes in left main PCI. Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  2. The impact of everolimus versus mycophenolate on blood and lymphocyte cyclosporine exposure in heart-transplant recipients

    DEFF Research Database (Denmark)

    Gustafsson, Finn; Barth, David; Delgado, Diego H

    2009-01-01

    CsA C2 levels and blood CsA AUC(0-12) in groups of patients treated with MMF or everolimus (R(2) 0.93 and 0.96, respectively; P 2) = 0.98), there was poor correlation...... between whole-blood C2 and lymphocyte AUC(0-12) in patients treated with everolimus (R(2) = 0.24). CONCLUSION: Standard blood CsA levels accurately predict intralymphocytic exposure to CsA in patients concomitantly treated with MMF but not in patients treated with everolimus........ METHODS: Twelve-hour pharmacokinetic studies of whole-blood and intralymphocytic CsA concentrations were conducted in long-term heart-transplant recipients treated with mycophenolate mofetil (MMF) + CsA (n = 8) and everolimus + CsA (n = 9). RESULTS: There was a highly significant correlation between blood...

  3. Everolimus in advanced, progressive, well-differentiated, non-functional neuroendocrine tumors: RADIANT-4 lung subgroup analysis.

    Science.gov (United States)

    Fazio, Nicola; Buzzoni, Roberto; Delle Fave, Gianfranco; Tesselaar, Margot E; Wolin, Edward; Van Cutsem, Eric; Tomassetti, Paola; Strosberg, Jonathan; Voi, Maurizio; Bubuteishvili-Pacaud, Lida; Ridolfi, Antonia; Herbst, Fabian; Tomasek, Jiri; Singh, Simron; Pavel, Marianne; Kulke, Matthew H; Valle, Juan W; Yao, James C

    2018-01-01

    In the phase III RADIANT-4 study, everolimus improved median progression-free survival (PFS) by 7.1 months in patients with advanced, progressive, well-differentiated (grade 1 or grade 2), non-functional lung or gastrointestinal neuroendocrine tumors (NETs) vs placebo (hazard ratio, 0.48; 95% confidence interval [CI], 0.35-0.67; P < .00001). This exploratory analysis reports the outcomes of the subgroup of patients with lung NETs. In RADIANT-4, patients were randomized (2:1) to everolimus 10 mg/d or placebo, both with best supportive care. This is a post hoc analysis of the lung subgroup with PFS, by central radiology review, as the primary endpoint; secondary endpoints included objective response rate and safety measures. Ninety of the 302 patients enrolled in the study had primary lung NET (everolimus, n = 63; placebo, n = 27). Median PFS (95% CI) by central review was 9.2 (6.8-10.9) months in the everolimus arm vs 3.6 (1.9-5.1) months in the placebo arm (hazard ratio, 0.50; 95% CI, 0.28-0.88). More patients who received everolimus (58%) experienced tumor shrinkage compared with placebo (13%). Most frequently reported (≥5% incidence) grade 3-4 drug-related adverse events (everolimus vs. placebo) included stomatitis (11% vs. 0%), hyperglycemia (10% vs. 0%), and any infections (8% vs. 0%). In patients with advanced, progressive, well-differentiated, non-functional lung NET, treatment with everolimus was associated with a median PFS improvement of 5.6 months, with a safety profile similar to that of the overall RADIANT-4 cohort. These results support the use of everolimus in patients with advanced, non-functional lung NET. The trial is registered with ClinicalTrials.gov (no. NCT01524783). © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  4. Everolimus for Previously Treated Advanced Gastric Cancer: Results of the Randomized, Double-Blind, Phase III GRANITE-1 Study

    Science.gov (United States)

    Ohtsu, Atsushi; Ajani, Jaffer A.; Bai, Yu-Xian; Bang, Yung-Jue; Chung, Hyun-Cheol; Pan, Hong-Ming; Sahmoud, Tarek; Shen, Lin; Yeh, Kun-Huei; Chin, Keisho; Muro, Kei; Kim, Yeul Hong; Ferry, David; Tebbutt, Niall C.; Al-Batran, Salah-Eddin; Smith, Heind; Costantini, Chiara; Rizvi, Syed; Lebwohl, David; Van Cutsem, Eric

    2013-01-01

    Purpose The oral mammalian target of rapamycin inhibitor everolimus demonstrated promising efficacy in a phase II study of pretreated advanced gastric cancer. This international, double-blind, phase III study compared everolimus efficacy and safety with that of best supportive care (BSC) in previously treated advanced gastric cancer. Patients and Methods Patients with advanced gastric cancer that progressed after one or two lines of systemic chemotherapy were randomly assigned to everolimus 10 mg/d (assignment schedule: 2:1) or matching placebo, both given with BSC. Randomization was stratified by previous chemotherapy lines (one v two) and region (Asia v rest of the world [ROW]). Treatment continued until disease progression or intolerable toxicity. Primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), overall response rate, and safety. Results Six hundred fifty-six patients (median age, 62.0 years; 73.6% male) were enrolled. Median OS was 5.4 months with everolimus and 4.3 months with placebo (hazard ratio, 0.90; 95% CI, 0.75 to 1.08; P = .124). Median PFS was 1.7 months and 1.4 months in the everolimus and placebo arms, respectively (hazard ratio, 0.66; 95% CI, 0.56 to 0.78). Common grade 3/4 adverse events included anemia, decreased appetite, and fatigue. The safety profile was similar in patients enrolled in Asia versus ROW. Conclusion Compared with BSC, everolimus did not significantly improve overall survival for advanced gastric cancer that progressed after one or two lines of previous systemic chemotherapy. The safety profile observed for everolimus was consistent with that observed for everolimus in other cancers. PMID:24043745

  5. Elution of Monomers from Provisional Composite Materials

    Directory of Open Access Journals (Sweden)

    Simon Daniel Schulz

    2015-01-01

    Full Text Available The aim of this study was to evaluate the elution of substances from different materials used for the manufacturing of temporary indirect restorations, after storage in saliva and ethanol 75%. 10 samples of three chemically cured materials (Protemp 3 Garant, Systemp.c&b, and Trim and one light-cured material (Clip F were stored in saliva and ethanol 75% for 24 h, 7, and days 28 days. From the storage media at each time period, samples were prepared and analysed by LC-MS/MS, in order to access the elution of monomers. The results differed among the materials (P ≤ 0.05. No monomers were detected in the samples of Protemp 3 Garant and Clip F. Substances were detected only in ethanol samples of Systemp.c&b and Trim. The amount of BisGMA, TEGDMA, and UDMA 2 released from Systemp.c&b was higher compared to Trim. Storage time affected the release of substances (P ≤ 0.05. The highest release was observed within the first 24 h. It can be concluded that provisional resin composite materials do not show high release of monomers and this release is material dependent. However, the detection of additional peaks during the analysis, suggesting the formation of by-products of the eluted substances, may not be in favour of these materials with respect to their toxicity.

  6. Transient coronary aneurysm formation after Nevo™ stent implantation versus persistent coronary aneurysm after Cypher Select™ stent implantation

    DEFF Research Database (Denmark)

    Christiansen, Evald Høj; Lassen, Jens Flensted; Jensen, Lisette Okkels

    2011-01-01

    We implanted a Cypher Select™ coronary stent and two months later a Nevo™ sirolimus-eluting coronary stent in another vessel. At a prescheduled angiographic follow-up, coronary aneurysms were seen in the two stented segments, 6 and 8 months after stent implantation, respectively. Six months later......, the aneurysm had healed in the Nevo, but was still present in the Cypher stented segment. We hypothesize that aneurysm formation was induced by sirolimus and the polymer of the implanted stents, and that subsequent healing was possible in the Nevo stent after degradation of the polymer....

  7. Innovative Elution Processes for Recovering Uranium from Seawater

    International Nuclear Information System (INIS)

    Wai, Chien; Tian, Guoxin; Janke, Christopher

    2014-01-01

    Utilizing amidoxime-based polymer sorbents for extraction of uranium from seawater has attracted considerable interest in recent years. Uranium collected in the sorbent is recovered typically by elution with an acid. One drawback of acid elution is deterioration of the sorbent which is a significant factor that limits the economic competitiveness of the amidoxime-based sorbent systems for sequestering uranium from seawater. Developing innovative elution processes to improve efficiency and to minimize loss of sorbent capacity become essential in order to make this technology economically feasible for large-scale industrial applications. This project has evaluated several elution processes including acid elution, carbonate elution, and supercritical fluid elution for recovering uranium from amidoxime-based polymer sorbents. The elution efficiency, durability and sorbent regeneration for repeated uranium adsorption- desorption cycles in simulated seawater have been studied. Spectroscopic techniques are used to evaluate chemical nature of the sorbent before and after elution. A sodium carbonate-hydrogen peroxide elution process for effective removal of uranium from amidoxime-based sorbent is developed. The cause of this sodium carbonate and hydrogen peroxide synergistic leaching of uranium from amidoxime-based sorbent is attributed to the formation of an extremely stable uranyl peroxo-carbonato complex. The efficiency of uranium elution by the carbonate-hydrogen peroxide method is comparable to that of the hydrochloric acid elution but damage to the sorbent material is much less for the former. The carbonate- hydrogen peroxide elution also does not need any elaborate step to regenerate the sorbent as those required for hydrochloric acid leaching. Several CO2-soluble ligands have been tested for extraction of uranium from the sorbent in supercritical fluid carbon dioxide. A mixture of hexafluoroacetylacetone and tri-n-butylphosphate shows the best result but uranium

  8. Innovative Elution Processes for Recovering Uranium from Seawater

    Energy Technology Data Exchange (ETDEWEB)

    Wai, Chien [Univ. of Idaho, Moscow, ID (United States); Tian, Guoxin [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Janke, Christopher [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2014-05-29

    Utilizing amidoxime-based polymer sorbents for extraction of uranium from seawater has attracted considerable interest in recent years. Uranium collected in the sorbent is recovered typically by elution with an acid. One drawback of acid elution is deterioration of the sorbent which is a significant factor that limits the economic competitiveness of the amidoxime-based sorbent systems for sequestering uranium from seawater. Developing innovative elution processes to improve efficiency and to minimize loss of sorbent capacity become essential in order to make this technology economically feasible for large-scale industrial applications. This project has evaluated several elution processes including acid elution, carbonate elution, and supercritical fluid elution for recovering uranium from amidoxime-based polymer sorbents. The elution efficiency, durability and sorbent regeneration for repeated uranium adsorption- desorption cycles in simulated seawater have been studied. Spectroscopic techniques are used to evaluate chemical nature of the sorbent before and after elution. A sodium carbonate-hydrogen peroxide elution process for effective removal of uranium from amidoxime-based sorbent is developed. The cause of this sodium carbonate and hydrogen peroxide synergistic leaching of uranium from amidoxime-based sorbent is attributed to the formation of an extremely stable uranyl peroxo-carbonato complex. The efficiency of uranium elution by the carbonate-hydrogen peroxide method is comparable to that of the hydrochloric acid elution but damage to the sorbent material is much less for the former. The carbonate- hydrogen peroxide elution also does not need any elaborate step to regenerate the sorbent as those required for hydrochloric acid leaching. Several CO2-soluble ligands have been tested for extraction of uranium from the sorbent in supercritical fluid carbon dioxide. A mixture of hexafluoroacetylacetone and tri-n-butylphosphate shows the best result but uranium

  9. Impact of prior therapies on everolimus activity: an exploratory analysis of RADIANT-4.

    Science.gov (United States)

    Buzzoni, Roberto; Carnaghi, Carlo; Strosberg, Jonathan; Fazio, Nicola; Singh, Simron; Herbst, Fabian; Ridolfi, Antonia; Pavel, Marianne E; Wolin, Edward M; Valle, Juan W; Oh, Do-Youn; Yao, James C; Pommier, Rodney

    2017-01-01

    Recently, everolimus was shown to improve median progression-free survival (PFS) by 7.1 months in patients with advanced, progressive, well-differentiated, nonfunctional neuroendocrine tumors (NET) of lung or gastrointestinal (GI) tract compared with placebo (HR, 0.48; 95% CI, 0.35-0.67; P <0.00001) in the Phase III, RADIANT-4 study. This post hoc analysis evaluates the impact of prior therapies (somatostatin analogs [SSA], chemotherapy, and radiotherapy) on everolimus activity. ClinicalTrials.gov identifier: NCT01524783. Patients were randomized (2:1) to everolimus 10 mg/day or placebo, both with best supportive care. Subgroups of patients who received prior SSA, chemotherapy, or radiotherapy (including peptide receptor radionuclide therapy) were analyzed and reported. A total of 302 patients were enrolled, of whom, 163 (54%) had any prior SSA use (mostly for tumor control), 77 (25%) received chemotherapy, and 63 (21%) were previously exposed to radiotherapy. Patients who received everolimus had longer median PFS compared with placebo, regardless of previous SSA (with SSA: 11.1 vs 4.5 months [HR, 0.56 {95% CI, 0.37-0.85}]; without SSA: 9.5 vs 3.7 months [0.57 {0.36-0.89}]), chemotherapy (with chemotherapy: 9.2 vs 2.1 months [0.35 {0.19-0.64}]; without chemotherapy: 11.2 vs 5.4 months [0.60 {0.42-0.86}]), or radiotherapy (with radiotherapy: 9.2 vs 3.0 months [0.47 {0.24-0.94}]; without radiotherapy: 11 vs 5.1 months [0.59 {0.42-0.83}]) exposure. The most frequent drug-related adverse events included stomatitis (59%-65%), fatigue (27%-35%), and diarrhea (24%-34%) among the subgroups. These results suggest that everolimus improves PFS in patients with advanced, progressive lung or GI NET, regardless of prior therapies. Safety findings were consistent with the known safety profile of everolimus in NET.

  10. Phase I-II study of everolimus and low-dose oral cyclophosphamide in patients with metastatic renal cell cancer

    International Nuclear Information System (INIS)

    Huijts, Charlotte M; Santegoets, Saskia J; Eertwegh, Alfons J van den; Pijpers, Laura S; Haanen, John B; Gruijl, Tanja D de; Verheul, Henk M; Vliet, Hans J van der

    2011-01-01

    For patients with metastatic renal cell cancer (mRCC) who progressed on vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor therapy, the orally administered mammalian target of rapamycin (mTOR) inhibitor everolimus has been shown to prolong progression free survival. Intriguingly, inhibition of mTOR also promotes expansion of immunosuppressive regulatory T cells (Tregs) that can inhibit anti-tumor immune responses in a clinically relevant way in various tumor types including RCC. This study intends to investigate whether the antitumor efficacy of everolimus can be increased by preventing the detrimental everolimus induced expansion of Tregs using a metronomic schedule of cyclophosphamide. This phase I-II trial is a national multi-center study of different doses and schedules of low-dose oral cyclophosphamide in combination with a fixed dose of everolimus in patients with mRCC not amenable to or progressive after a VEGF-receptor tyrosine kinase inhibitor containing treatment regimen. In the phase I part of the study the optimal Treg-depleting dose and schedule of metronomic oral cyclophosphamide when given in combination with everolimus will be determined. In the phase II part of the study we will evaluate whether the percentage of patients progression free at 4 months of everolimus treatment can be increased from 50% to 70% by adding metronomic cyclophosphamide (in the dose and schedule determined in the phase I part). In addition to efficacy, we will perform extensive immune monitoring with a focus on the number, phenotype and function of Tregs, evaluate the safety and feasibility of the combination of everolimus and cyclophosphamide, perform monitoring of selected angiogenesis parameters and analyze everolimus and cyclophosphamide drug levels. This phase I-II study is designed to determine whether metronomic cyclophosphamide can be used to counter the mTOR inhibitor everolimus induced Treg expansion in patients with metastatic renal cell

  11. Phase I-II study of everolimus and low-dose oral cyclophosphamide in patients with metastatic renal cell cancer

    Directory of Open Access Journals (Sweden)

    Huijts Charlotte M

    2011-11-01

    Full Text Available Abstract Background For patients with metastatic renal cell cancer (mRCC who progressed on vascular endothelial growth factor (VEGF receptor tyrosine kinase inhibitor therapy, the orally administered mammalian target of rapamycin (mTOR inhibitor everolimus has been shown to prolong progression free survival. Intriguingly, inhibition of mTOR also promotes expansion of immunosuppressive regulatory T cells (Tregs that can inhibit anti-tumor immune responses in a clinically relevant way in various tumor types including RCC. This study intends to investigate whether the antitumor efficacy of everolimus can be increased by preventing the detrimental everolimus induced expansion of Tregs using a metronomic schedule of cyclophosphamide. Methods/design This phase I-II trial is a national multi-center study of different doses and schedules of low-dose oral cyclophosphamide in combination with a fixed dose of everolimus in patients with mRCC not amenable to or progressive after a VEGF-receptor tyrosine kinase inhibitor containing treatment regimen. In the phase I part of the study the optimal Treg-depleting dose and schedule of metronomic oral cyclophosphamide when given in combination with everolimus will be determined. In the phase II part of the study we will evaluate whether the percentage of patients progression free at 4 months of everolimus treatment can be increased from 50% to 70% by adding metronomic cyclophosphamide (in the dose and schedule determined in the phase I part. In addition to efficacy, we will perform extensive immune monitoring with a focus on the number, phenotype and function of Tregs, evaluate the safety and feasibility of the combination of everolimus and cyclophosphamide, perform monitoring of selected angiogenesis parameters and analyze everolimus and cyclophosphamide drug levels. Discussion This phase I-II study is designed to determine whether metronomic cyclophosphamide can be used to counter the mTOR inhibitor everolimus

  12. Coronary Stents: The Impact of Technological Advances on Clinical Outcomes.

    Science.gov (United States)

    Mennuni, Marco G; Pagnotta, Paolo A; Stefanini, Giulio G

    2016-02-01

    Percutaneous coronary interventions (PCI) were proposed in the late 1970s as an alternative to surgical coronary artery bypass grafting for the treatment of coronary artery disease. Important technological progress has been made since. Balloon angioplasty was replaced by bare metal stents, which allowed to permanently scaffold the coronary vessel avoiding acute recoil and abrupt occlusion. Thereafter, the introduction of early generation drug-eluting stents (DES) has significantly improved clinical outcomes, primarily by markedly reducing the risk of restenosis. New generation DES with thinner stent struts, novel durable or biodegradable polymer coatings, and new limus antiproliferative agents, have further improved upon the safety and efficacy profile of early generation DES. The present article aims to review the impact of technological advances on clinical outcomes in the field of PCI with coronary stents, and to provide a brief overview on clinical margins of improvement and unmet needs of available DES.

  13. Critical appraisal of the role of everolimus in advanced neuroendocrine tumors of pancreatic origin

    Directory of Open Access Journals (Sweden)

    Mulet-Margalef N

    2012-09-01

    Full Text Available Núria Mulet-Margalef, Jaume CapdevilaMedical Oncology Department, Vall d'Hebron University Hospital, Barcelona, SpainAbstract: For many years, the treatment of advanced pancreatic neuroendocrine tumors (pNETs has been limited almost entirely to somatostatin analogs and streptozocin-based chemotherapy, with modest benefit. Increasing knowledge of the biologic features of pNETs has allowed the design of molecular-based clinical trials, which have taken a step forward in the management of these tumors. In this review, we discuss the molecular rationale for the development of everolimus for patients with advanced pNETs, critically review the clinical data obtained by the main studies in this setting, and discuss essential considerations based on recent findings in pNET biology for future drug development involving the phosphatidylinositol 3' kinase-AKT-mTOR pathway.Keywords: pancreatic neuroendocrine tumors, everolimus, targeted therapies

  14. Everolimus: the first approved product for patients with advanced renal cell cancer after sunitinib and/or sorafenib

    Directory of Open Access Journals (Sweden)

    Chris Coppin

    2010-04-01

    Full Text Available Chris CoppinMedical Oncology, BC Cancer Agency and University of British Columbia, Vancouver, CanadaAbstract: Everolimus (RAD001, Afinitor® Novartis is the first oral inhibitor of mTOR (mammalian target of rapamycin to reach the oncology clinic. Everolimus 10 mg daily achieves complete inhibition of its target at below the maximum tolerable dose for most patients. A phase III randomized placebo-controlled trial has examined the impact of everolimus in patients with clear cell renal cancers and progressive disease on or within 6 months of the VEGFR tyrosine kinase inhibitors sunitinib and/or sorafenib. The primary endpoint of progression-free survival was increased from median 1.9 to 4.9 months (hazard ratio 0.33, P < 0.001 and 25% were still progression-free after 10 months of everolimus therapy. There was a delay in time to decline of performance status and trends to improvement in quality of life, disease-related symptoms, and overall survival despite crossover of the majority of patients assigned to placebo. In 2009, everolimus was approved in the US and Europe as the only validated option for this indication. Toxicities are usually mild to moderate and can be managed with dose reduction or interruption if necessary. Opportunistic infections and non-infectious pneumonitis are seen as a class effect. Management of common practical management issues are discussed. Clinical trials are in progress to examine additional roles for everolimus in renal cancer, alone and in combination with other agents.Keywords: everolimus, drug therapy, advanced renal cancer

  15. Therapeutic potential and adverse events of everolimus for treatment of hepatocellular carcinoma – systematic review and meta-analysis

    International Nuclear Information System (INIS)

    Yamanaka, Kenya; Petrulionis, Marius; Lin, Shibo; Gao, Chao; Galli, Uwe; Richter, Susanne; Winkler, Susanne; Houben, Philipp; Schultze, Daniel; Hatano, Etsuro; Schemmer, Peter

    2013-01-01

    Everolimus is an orally administrated mammalian target of rapamycin (mTOR) inhibitor. Several large-scale randomized controlled trials (RCTs) have demonstrated the survival benefits of everolimus at the dose of 10 mg/day for solid cancers. Furthermore, mTOR-inhibitor-based immunosuppression is associated with survival benefits for patients with hepatocellular carcinoma (HCC) who have received liver transplantation. However, a low rate of tumor reduction and some adverse events have been pointed out. This review summarizes the antitumor effects and adverse events of everolimus and evaluates its possible application in advanced HCC. For the meta-analysis of adverse events, we used the RCTs for solid cancers. The odds ratios of adverse events were calculated using the Peto method. Manypreclinical studies demonstrated that everolimus had antitumor effects such as antiproliferation and antiangiogenesis. However, some differences in the effects were observed among in vivo animal studies for HCC treatment. Meanwhile, clinical studies demonstrated that the response rate of single-agent everolimus was low, though survival benefits could be expected. The meta-analysis revealed the odds ratios (95% confidence interval [CI]) of stomatitis: 5.42 [4.31–6.73], hyperglycemia: 3.22 [2.37–4.39], anemia: 3.34 [2.37–4.67], pneumonitis: 6.02 [3.95–9.16], aspartate aminotransferase levels: 2.22 [1.37–3.62], and serum alanine aminotransferase levels: 2.94 [1.72–5.02], respectively. Everolimus at the dose of 10 mg/day significantly increased the risk of the adverse events. In order to enable its application to the standard conventional therapies of HCC, further studies are required to enhance the antitumor effects and manage the adverse events of everolimus

  16. Two-dose-level confirmatory study of the pharmacokinetics and tolerability of everolimus in Chinese patients with advanced solid tumors

    Directory of Open Access Journals (Sweden)

    Jappe Annette

    2011-01-01

    Full Text Available Abstract Background This phase I, randomized, multicenter, open-label study investigated the pharmacokinetics, safety, and efficacy of the oral mammalian target of rapamycin inhibitor everolimus in Chinese patients with advanced solid tumors. Methods A total of 24 patients with advanced breast cancer (n = 6, gastric cancer (n = 6, non-small cell lung cancer (n = 6, or renal cell carcinoma (n = 6 who were refractory to/unsuitable for standard therapy were randomized 1:1 to oral everolimus 5 or 10 mg/day. Primary end points were pharmacokinetic parameters and safety and tolerability. Pharmacokinetic 24-h profiles were measured on day 15; trough level was measured on days 2, 8, 15, 16, and 22. Tolerability was assessed continuously. This final analysis was performed after all patients had received 6 months of study drug or had discontinued. Results Everolimus was absorbed rapidly; median Tmax was 3 h (range, 1-4 and 2 h (range, 0.9-6 in the 5 and 10 mg/day groups, respectively. Pharmacokinetic parameters increased dose proportionally from the 5 and 10 mg/day doses. Steady-state levels were achieved by day 8 or earlier. The most common adverse events suspected to be related to everolimus therapy were increased blood glucose (16.7% and 41.7% and fatigue (16.7% and 33.3% in the everolimus 5 and 10 mg/day dose cohorts, respectively. Best tumor response was stable disease in 10 (83% and 6 (50% patients in the 5 and 10 mg/day groups, respectively. Conclusions Everolimus 5 or 10 mg/day was well tolerated in Chinese patients with advanced solid tumors. The observed safety and pharmacokinetic profile of everolimus from this study were consistent with previous studies. Trial registration Chinese Health Authorities 2008L09346

  17. Efficacy and Safety of Drug-Eluting Stents in the Real World: 8-Year Follow-Up

    Energy Technology Data Exchange (ETDEWEB)

    Pellegrini, Denise Oliveira, E-mail: dennizmo@yahoo.com.br; Gomes, Vitor Osório; Lasevitch, Ricardo; Smidt, Luis; Azeredo, Marco Aurélio; Ledur, Priscila; Bodanese, Rodrigo; Sinnott, Leonardo; Moriguchi, Emílio; Caramori, Paulo [Hospital São Lucas PUC, Porto Alegre, RS (Brazil)

    2014-09-15

    Drug-eluting stents have been used in daily practice since 2002, with the clear advantages of reducing the risk of target vessel revascularization and an impressive reduction in restenosis rate by 50%-70%. However, the occurrence of a late thrombosis can compromise long-term results, particularly if the risks of this event were sustained. In this context, a registry of clinical cases gains special value. To evaluate the efficacy and safety of drug-eluting stents in the real world. We report on the clinical findings and 8-year follow-up parameters of all patients that underwent percutaneous coronary intervention with a drug-eluting stent from January 2002 to April 2007. Drug-eluting stents were used in accordance with the clinical and interventional cardiologist decision and availability of the stent. A total of 611 patients were included, and clinical follow-up of up to 8 years was obtained for 96.2% of the patients. Total mortality was 8.7% and nonfatal infarctions occurred in 4.3% of the cases. Target vessel revascularization occurred in 12.4% of the cases, and target lesion revascularization occurred in 8% of the cases. The rate of stent thrombosis was 2.1%. There were no new episodes of stent thrombosis after the fifth year of follow-up. Comparative subanalysis showed no outcome differences between the different types of stents used, including Cypher®, Taxus®, and Endeavor®. These findings indicate that drug-eluting stents remain safe and effective at very long-term follow-up. Patients in the 'real world' may benefit from drug-eluting stenting with excellent, long-term results.

  18. Supplementary Administration of Everolimus Reduces Cardiac Systolic Function in Kidney Transplant Recipients.

    Science.gov (United States)

    Tsujimura, Kazuma; Ota, Morihito; Chinen, Kiyoshi; Nagayama, Kiyomitsu; Oroku, Masato; Nishihira, Morikuni; Shiohira, Yoshiki; Abe, Masami; Iseki, Kunitoshi; Ishida, Hideki; Tanabe, Kazunari

    2017-05-26

    BACKGROUND The effect of everolimus, one of the mammalian targets of rapamycin inhibitors, on cardiac function was evaluated in kidney transplant recipients. MATERIAL AND METHODS Seventy-six participants who underwent kidney transplant between March 2009 and May 2016 were retrospectively reviewed. To standardize everolimus administration, the following criteria were used: (1) the recipient did not have a donor-specific antigen before kidney transplantation; (2) the recipient did not have proteinuria and uncontrollable hyperlipidemia after kidney transplantation; and (3) acute rejection was not observed on protocol biopsy 3 months after kidney transplantation. According to these criteria, everolimus administration for maintenance immunosuppression after kidney transplantation was included. Cardiac function was compared between the treatment group (n=30) and non-treatment group (n=46). RESULTS The mean observation periods of the treatment and non-treatment groups were 41.3±12.6 and 43.9±19.8 months, respectively (p=0.573). The mean ejection fraction and fractional shortening of the treatment and non-treatment groups after kidney transplant were 66.5±7.9% vs. 69.6±5.5% (p=0.024) and 37.1±6.2% vs. 39.3±4.7% (p=0.045), respectively. In the treatment group, the mean ejection fraction and fractional shortening before and after kidney transplantation did not differ significantly (p=0.604 and 0.606, respectively). In the non-treatment group, the mean ejection fraction and fractional shortening before and after kidney transplantation differed significantly (p=0.004 and 0.006, respectively). CONCLUSIONS Supplementary administration of everolimus after kidney transplantation can reduce cardiac systolic function.

  19. Comparison of newer-generation drug-eluting with bare-metal stents in patients with acute ST-segment elevation myocardial infarction: a pooled analysis of the EXAMINATION (clinical Evaluation of the Xience-V stent in Acute Myocardial INfArcTION) and COMFORTABLE-AMI (Comparison of Biolimus Eluted From an Erodible Stent Coating With Bare Metal Stents in Acute ST-Elevation Myocardial Infarction) trials.

    Science.gov (United States)

    Sabaté, Manel; Räber, Lorenz; Heg, Dik; Brugaletta, Salvatore; Kelbaek, Henning; Cequier, Angel; Ostojic, Miodrag; Iñiguez, Andrés; Tüller, David; Serra, Antonio; Baumbach, Andreas; von Birgelen, Clemens; Hernandez-Antolin, Rosana; Roffi, Marco; Mainar, Vicente; Valgimigli, Marco; Serruys, Patrick W; Jüni, Peter; Windecker, Stephan

    2014-01-01

    This study sought to study the efficacy and safety of newer-generation drug-eluting stents (DES) compared with bare-metal stents (BMS) in an appropriately powered population of patients with ST-segment elevation myocardial infarction (STEMI). Among patients with STEMI, early generation DES improved efficacy but not safety compared with BMS. Newer-generation DES, everolimus-eluting stents, and biolimus A9-eluting stents, have been shown to improve clinical outcomes compared with early generation DES. Individual patient data for 2,665 STEMI patients enrolled in 2 large-scale randomized clinical trials comparing newer-generation DES with BMS were pooled: 1,326 patients received a newer-generation DES (everolimus-eluting stent or biolimus A9-eluting stent), whereas the remaining 1,329 patients received a BMS. Random-effects models were used to assess differences between the 2 groups for the device-oriented composite endpoint of cardiac death, target-vessel reinfarction, and target-lesion revascularization and the patient-oriented composite endpoint of all-cause death, any infarction, and any revascularization at 1 year. Newer-generation DES substantially reduce the risk of the device-oriented composite endpoint compared with BMS at 1 year (relative risk [RR]: 0.58; 95% confidence interval [CI]: 0.43 to 0.79; p = 0.0004). Similarly, the risk of the patient-oriented composite endpoint was lower with newer-generation DES than BMS (RR: 0.78; 95% CI: 0.63 to 0.96; p = 0.02). Differences in favor of newer-generation DES were driven by both a lower risk of repeat revascularization of the target lesion (RR: 0.33; 95% CI: 0.20 to 0.52; p stent thrombosis (RR: 0.35; 95% CI: 0.16 to 0.75; p = 0.006) compared with BMS. Among patients with STEMI, newer-generation DES improve safety and efficacy compared with BMS throughout 1 year. It remains to be determined whether the differences in favor of newer-generation DES are sustained during long-term follow-up. Copyright © 2014 American

  20. Safety, Efficacy, and Patient Acceptability of Everolimus in the Treatment of Breast Cancer.

    Science.gov (United States)

    Lousberg, Laurence; Jerusalem, Guy

    2016-01-01

    Everolimus combined with exemestane is an important treatment option for patients suffering from estrogen receptor-positive, human epidermal growth factor receptor 2-negative, advanced breast cancer (ABC) who have been previously treated with a nonsteroidal aromatase inhibitor (NSAI). After presentation of phase III registration trial BOLERO-2, several phase IIIb trials have been started to evaluate this regimen in a more real-world setting. Here, we review the efficacy and safety data published or presented at selected international meetings. These studies confirmed the outcome observed in the BOLERO-2 trial. Patient acceptance rate is also discussed by focusing on the permanent everolimus discontinuation rate in these trials. Factors influencing the safety profile are also reported, including the impact of age. The optimal sequence of combined therapy approaches associating targeted and endocrine therapy (ET) has yet to be determined as new treatment options such as cyclin-dependent kinase inhibitors become available. However, everolimus-exemestane remains an important treatment option with a major impact on progression-free survival (PFS) and an acceptable safety profile.

  1. Use of drug-eluting stents in Victorian public hospitals.

    Science.gov (United States)

    Yan, Bryan P; Ajani, Andrew E; Duffy, Stephen J; New, Gishel; Horrigan, Mark; Szto, Gregory; Walton, Antony; Eccleston, David; Lefkovits, Jeffery; Black, Alexander; Sebastian, Martin; Brennan, Angela L; Reid, Christopher M; Clark, David J

    2006-10-02

    We aimed to assess the pattern of use of drug-eluting stents (DESs) in patients undergoing percutaneous coronary interventions (PCIs) in Victorian public hospitals. Prospective study comparing the use of one or more DESs versus bare-metal stents (BMSs) only, in consecutive patients undergoing 2428 PCIs with stent implantation from 1 April 2004 to 31 December 2005 at seven Victorian public hospitals. Adherence to current Victorian Department of Human Services guidelines which recommend DES use in patients with high-risk features for restenosis (diabetes, small vessels, long lesions, in-stent restenotic lesions, chronic total occlusions and bifurcation lesions). Of the 2428 PCIs performed, at least one DES was implanted in 1101 (45.3%) and BMSs only were implanted in 1327 (54.7%). In 87.7% (966/1101) of PCI with DESs, there was at least one criterion for high risk of restenosis. DESs were more likely to be used in patients with diabetes (risk ratio [RR], 2.45; 95% CI, 2.02-2.97), small vessels (RR, 3.35; 95%CI, 2.35-4.76), long lesions (RR, 3.87; 95% CI, 3.23-4.65), in-stent restenotic lesions (RR, 3.98; 95%CI, 2.67-6.06), chronic total occlusions (RR, 1.30; 95% CI, 0.51-2.88) and bifurcation lesions (RR, 2.23; 95%CI, 1.57-3.17). However, 66.2% (1608/2428) of all PCIs were in patients eligible for DESs according to Victorian guidelines, and in 39.9% (642/1608) of these PCIs, a BMS was used. In Victorian public hospitals, DESs have been largely reserved for patients at high risk of restenosis in accordance with Department of Human Services guidelines. However, many patients with high-risk criteria for restenosis did not receive DESs. Greater use of DESs in these patients may improve outcomes by reducing the need for repeat revascularisation.

  2. 18F-FDG and 18F-FLT-PET Imaging for Monitoring Everolimus Effect on Tumor-Growth in Neuroendocrine Tumors

    DEFF Research Database (Denmark)

    Johnbeck, Camilla Bardram; Munk Jensen, Mette; Nielsen, Carsten Haagen

    2014-01-01

    INTRODUCTION: The mTOR inhibitor everolimus has shown promising results in some but not all neuroendocrine tumors. Therefore, early assessment of treatment response would be beneficial. In this study, we investigated the in vivo and in vitro treatment effect of everolimus in neuroendocrine tumors...

  3. Long-term outcomes of thoracic transplant recipients following conversion to everolimus with reduced calcineurin inhibitor in a multicenter, open-label, randomized trial lv

    DEFF Research Database (Denmark)

    Gullestad, Lars; Eiskjaer, Hans; Gustafsson, Finn

    2016-01-01

    The NOCTET study randomized 282 patients ≥1 year after heart or lung transplantation to continue conventional calcineurin inhibitor (CNI) therapy or to start everolimus with reduced-exposure CNI. Last follow-up, at ≥5 years postrandomization (mean: 5.6 years) was attended by 72/140 everolimus...

  4. The MANDELA study: A multicenter, randomized, open-label, parallel group trial to refine the use of everolimus after heart transplantation.

    Science.gov (United States)

    Deuse, Tobias; Bara, Christoph; Barten, Markus J; Hirt, Stephan W; Doesch, Andreas O; Knosalla, Christoph; Grinninger, Carola; Stypmann, Jörg; Garbade, Jens; Wimmer, Peter; May, Christoph; Porstner, Martina; Schulz, Uwe

    2015-11-01

    In recent years a series of trials has sought to define the optimal protocol for everolimus-based immunosuppression in heart transplantation, with the goal of minimizing exposure to calcineurin inhibitors (CNIs) and harnessing the non-immunosuppressive benefits of everolimus. Randomized studies have demonstrated that immunosuppressive potency can be maintained in heart transplant patients receiving everolimus despite marked CNI reduction, although very early CNI withdrawal may be inadvisable. A potential renal advantage has been shown for everolimus, but the optimal time for conversion and the adequate reduction in CNI exposure remain to be defined. Other reasons for use of everolimus include a substantial reduction in the risk of cytomegalovirus infection, and evidence for inhibition of cardiac allograft vasculopathy, a major cause of graft loss. The ongoing MANDELA study is a 12-month multicenter, randomized, open-label, parallel-group study in which efficacy, renal function and safety are compared in approximately 200 heart transplant patients. Patients receive CNI therapy, steroids and everolimus or mycophenolic acid during months 3 to 6 post-transplant, and are then randomized at month 6 post-transplant (i) to convert to CNI-free immunosuppression with everolimus and mycophenolic acid or (ii) to continue reduced-exposure CNI, with concomitant everolimus. Patients are then followed to month 18 post-transplant The rationale and expectations for the trial and its methodology are described herein. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Everolimus long-term use in patients with tuberous sclerosis complex: Four-year update of the EXIST-2 study.

    Directory of Open Access Journals (Sweden)

    John J Bissler

    Full Text Available We examined the long-term effects of everolimus in patients with renal angiomyolipoma associated with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis.Following favorable results from the double-blind core phase of EXIST-2 (NCT00790400, patients were allowed to receive open-label everolimus (extension phase. Patients initially randomly assigned to everolimus continued on the same dose; those who were receiving placebo crossed over to everolimus 10 mg/day. Dose modifications were based on tolerability. The primary end point was angiomyolipoma response rate, defined as a ≥50% reduction from baseline in the sum volume of target renal angiomyolipomas in the absence of new target angiomyolipomas, kidney volume increase of >20% from nadir, and angiomyolipoma-related bleeding grade ≥2. The key secondary end point was safety.Of the 112 patients who received ≥1 dose of everolimus, 58% (95% CI, 48.3% to 67.3% achieved angiomyolipoma response. Almost all patients (97% experienced reduction in renal lesion volumes at some point during the study period. Median duration of everolimus exposure was 46.9 months. Sixteen (14.3% patients experienced angiomyolipoma progression at some point in the study. No angiomyolipoma-related bleeding or nephrectomies were reported. One patient on everolimus underwent embolization for worsening right flank pain. Subependymal giant cell astrocytoma lesion response was achieved in 48% of patients and skin lesion response in 68% of patients. The most common adverse events suspected to be treatment-related were stomatitis (42%, hypercholesterolemia (30.4%, acne (25.9%, aphthous stomatitis and nasopharyngitis (each 21.4%. Ten (8.9% patients withdrew because of an adverse event. Renal function remained stable, and the frequency of emergent adverse events generally decreased over time.Everolimus treatment remained safe and effective over approximately 4 years. The overall risk/benefit assessment supports the use

  6. Everolimus plus exemestane in postmenopausal patients with HR(+) breast cancer: BOLERO-2 final progression-free survival analysis.

    Science.gov (United States)

    Yardley, Denise A; Noguchi, Shinzaburo; Pritchard, Kathleen I; Burris, Howard A; Baselga, José; Gnant, Michael; Hortobagyi, Gabriel N; Campone, Mario; Pistilli, Barbara; Piccart, Martine; Melichar, Bohuslav; Petrakova, Katarina; Arena, Francis P; Erdkamp, Frans; Harb, Wael A; Feng, Wentao; Cahana, Ayelet; Taran, Tetiana; Lebwohl, David; Rugo, Hope S

    2013-10-01

    Effective treatments for hormone-receptor-positive (HR(+)) breast cancer (BC) following relapse/progression on nonsteroidal aromatase inhibitor (NSAI) therapy are needed. Initial Breast Cancer Trials of OraL EveROlimus-2 (BOLERO-2) trial data demonstrated that everolimus and exemestane significantly prolonged progression-free survival (PFS) versus placebo plus exemestane alone in this patient population. BOLERO-2 is a phase 3, double-blind, randomized, international trial comparing everolimus (10 mg/day) plus exemestane (25 mg/day) versus placebo plus exemestane in postmenopausal women with HR(+) advanced BC with recurrence/progression during or after NSAIs. The primary endpoint was PFS by local investigator review, and was confirmed by independent central radiology review. Overall survival, response rate, and clinical benefit rate were secondary endpoints. Final study results with median 18-month follow-up show that median PFS remained significantly longer with everolimus plus exemestane versus placebo plus exemestane [investigator review: 7.8 versus 3.2 months, respectively; hazard ratio = 0.45 (95% confidence interval 0.38-0.54); log-rank P NSAIs. These results further support the use of everolimus plus exemestane in this patient population. ClinicalTrials.gov #NCT00863655.

  7. FDG-PET as a predictive biomarker for therapy with everolimus in metastatic renal cell cancer

    International Nuclear Information System (INIS)

    Chen, James L; Appelbaum, Daniel E; Kocherginsky, Masha; Cowey, Charles L; Kimryn Rathmell, Wendy; McDermott, David F; Stadler, Walter M

    2013-01-01

    The mTOR (mammalian target of rapamycin) inhibitor, everolimus, affects tumor growth by targeting cellular metabolic proliferation pathways and delays renal cell carcinoma (RCC) progression. Preclinical evidence suggests that baseline elevated tumor glucose metabolism as quantified by FDG-PET ([ 18 F] fluorodeoxy-glucose positron emission tomography) may predict antitumor activity. Metastatic RCC (mRCC) patients refractory to vascular endothelial growth factor (VEGF) pathway inhibition were treated with standard dose everolimus. FDG-PET scans were obtained at baseline and 2 weeks; serial computed tomography (CT) scans were obtained at baseline and every 8 weeks. Maximum standardized uptake value (SUVmax) of the most FDG avid lesion, average SUVmax of all measured lesions and their corresponding 2-week relative changes were examined for association with 8-week change in tumor size. A total of 63 patients were enrolled; 50 were evaluable for the primary endpoint of which 48 had both PET scans. Patient characteristics included the following: 36 (72%) clear cell histology and median age 59 (range: 37–80). Median pre- and 2-week treatment average SUVmax were 6.6 (1–17.9) and 4.2 (1–13.9), respectively. Response evaluation criteria in solid tumors (RECIST)-based measurements demonstrated an average change in tumor burden of 0.2% (−32.7% to 35.9%) at 8 weeks. Relative change in average SUVmax was the best predictor of change in tumor burden (all evaluable P = 0.01; clear cell subtype P = 0.02), with modest correlation. Baseline average SUVmax was correlated with overall survival and progression-free survival (PFS) (P = 0.023; 0.020), but not with change in tumor burden. Everolimus therapy decreased SUVs on follow-up PET scans in mRCC patients, but changes were only modestly correlated with changes in tumor size. Thus, clinical use of FDG-PET-based biomarkers is challenged by high variability. In this phase II trial, FDG-PET was explored as a predictive biomarker

  8. Disappearing and reappearing differences in drug-eluting stent use by race.

    Science.gov (United States)

    Federspiel, Jerome J; Stearns, Sally C; Reiter, Kristin L; Geissler, Kimberley H; Triplette, Matthew A; D'Arcy, Laura P; Sheridan, Brett C; Rossi, Joseph S

    2013-04-01

    Drug-eluting coronary stents (DES) rapidly dominated the marketplace in the United States after approval in 2003, but utilization rates were initially lower among African American patients. We assess whether racial differences persisted as DES diffused into practice. Medicare claims data were used to identify coronary stenting procedures among elderly patients with acute coronary syndromes (ACS). Regression models of the choice of DES versus bare mental stent controlled for demographics, ACS type, co-morbidities and hospital characteristics. Diffusion was assessed in the short run (2003-2004) and long run (2007), with the effect of race calculated to allow for time-varying effects. The sample included 381,887 Medicare beneficiaries treated with stent insertion; approximately 5% were African American. Initially (May 2003-February 2004), African American race was associated with lower DES use compared to other races (44.3% versus 46.5%, P differences were not significant (79.8% versus 80.3%, P = 0.45). Subsequent concerns regarding DES safety caused reductions in DES use, with African Americans having lower use than other racial groups in 2007 (63.1% versus 65.2%, P differences in race reflect decisions regarding treatment appropriateness. © 2011 Blackwell Publishing Ltd.

  9. First-generation versus second-generation drug-eluting stents in current clinical practice: updated evidence from a comprehensive meta-analysis of randomised clinical trials comprising 31 379 patients

    NARCIS (Netherlands)

    Navarese, E.P.; Kowalewski, M.; Kandzari, D.; Lansky, A.; Gorny, B.; Koltowski, L.; Waksman, R.; Berti, S.; Musumeci, G.; Limbruno, U.; Schaaf, R.J. van der; Kelm, M.; Kubica, J.; Suryapranata, H.

    2014-01-01

    BACKGROUND: First-generation drug-eluting stents (DES) have become the most widely used devices worldwide for management of coronary artery disease. As remote follow-up data were becoming available, concerns emerged in regard to their long-term safety. Second-generation DES were designed to overcome

  10. Hypotonic elution, a new desorption principle in immunoadsorbent chromatography

    DEFF Research Database (Denmark)

    Danielsen, Erik Michael; Sjöström, H; Norén, O

    1982-01-01

    of finding an efficient means of elution which is not denaturing to neither the purified enzyme nor the immunoadsorbent column. Common properties of the microvillar enzymes with regard to amphiphilicity, glycosylation or subunit composition could hypothetically account for the similar elution properties...

  11. Efficacy and Safety of Everolimus for Maintenance Immunosuppression of Kidney Transplantation: A Meta-Analysis of Randomized Controlled Trials.

    Directory of Open Access Journals (Sweden)

    Jinyu Liu

    Full Text Available Conversion to everolimus is often used in kidney transplantation to overcome calcineurin inhibitor (CNI nephrotoxicity but there is conflicting evidence for this approach.To investigate the benefits and harm from randomized clinical trials (RCTs involving the conversion from CNI to everolimus after kidney transplantation.Databases were searched up to March 2016. Two reviewers independently assessed trials for eligibility and quality, and extracted data. Results are expressed as risk ratio (RR or mean difference (MD with 95% confidence intervals (CI.Eleven RCTs, with a total of 1,633 patients, met the final inclusion criteria. Patients converted to everolimus had improved renal function at 1 year posttransplant with an estimated glomerular filtration rate (eGFR of 5.36 mL/min per 1.73 m2 greater than patients remaining on CNI (p = 0.0005 and the longer-term results (> 1 year of renal function was identical to that of 1 year. There was not a substantial difference in graft loss, mortality, and the occurrence of adverse events (AEs or serious AEs. However, the risks of acute rejection and trial termination due to AEs with everolimus are respectively 1.82 and 2.63 times greater than patients staying on CNI at 1 year posttransplant (p = 0.02, p = 0.03, respectively. Further, those patients who converted to everolimus had a substantially greater risk of anemia, hyperlipidemia, hypercholesterolemia, hypokalemia, proteinuria, stomatitis, mouth ulceration, and acne.Conversion from CNI to everolimus after kidney transplantation is associated with improved renal function in the first 5 years posttransplant but increases the risk of acute rejection at 1 year posttransplant and may not be well endured.

  12. Mechanisms and Patterns of Intravascular Ultrasound In-Stent Restenosis Among Bare Metal Stents and First- and Second-Generation Drug-Eluting Stents.

    Science.gov (United States)

    Goto, Kosaku; Zhao, Zhijing; Matsumura, Mitsuaki; Dohi, Tomotaka; Kobayashi, Nobuaki; Kirtane, Ajay J; Rabbani, LeRoy E; Collins, Michael B; Parikh, Manish A; Kodali, Susheel K; Leon, Martin B; Moses, Jeffrey W; Mintz, Gary S; Maehara, Akiko

    2015-11-01

    The most common causes of in-stent restenosis (ISR) are intimal hyperplasia and stent under expansion. The purpose of this study was to use intravascular ultrasound (IVUS) to compare the ISR mechanisms of bare metal stents (BMS), first-generation drug-eluting stents (DES), and second-generation DES. There were 298 ISR lesions including 52 BMS, 73 sirolimus-eluting stents, 52 paclitaxel-eluting stents, 16 zotarolimus-eluting stents, and 105 everolimus-eluting stent. Mean patient age was 66.6 ± 1.1 years, 74.2% were men, and 48.3% had diabetes mellitus. BMS restenosis presented later (70.0 ± 66.7 months) with more intimal hyperplasia compared with DES (BMS 58.6 ± 15.5%, first-generation DES 52.6 ± 20.9%, second-generation DES 48.2 ± 22.2%, p = 0.02). Although reference lumen areas were similar in BMS and first- and second-generation DES, restenotic DES were longer (BMS 21.8 ± 13.5 mm, first-generation DES 29.4 ± 16.1 mm, second-generation DES 32.1 ± 18.7 mm, p = 0.003), and stent areas were smaller (BMS 7.2 ± 2.4 mm(2), first-generation DES 6.1 ± 2.1 mm(2), second-generation DES 5.7 ± 2.0 mm(2), p Stent fracture was seen only in DES (first-generation DES 7 [5.0%], second-generation DES 8 [7.4%], p = 0.13). In conclusion, restenotic first- and second-generation DES were characterized by less neointimal hyperplasia, smaller stent areas, longer stent lengths, and more stent fractures than restenotic BMS. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Production of 99Tc generators with automatic elution

    International Nuclear Information System (INIS)

    Mengatti, J.; Yanagawa, S.T.I.; Mazzarro, E.; Gasiglia, H.T.; Rela, P.R.; Silva, C.P.G. da; Pereira, N.P.S. de.

    1983-10-01

    The improvements performed on the routine production of sup(99m) Tc-generators at the Instituto de Pesquisas Energeticas e Nucleares-CNEN/SP, are described. The old model generators (manual elution of sup(99m) Tc) were substituted by automatically eluted generators (Vacuum system). The alumina column, elution system and acessories were modified; the elution time was reduced from 60 to 20-30 seconds. The new generators give 80-90% elution yields using six mililiters of sodium chloride 0,9% as sup(99m) Tc eluant instead of the 10 mililiters necessary to eluate the old generators. So, the radioactive concentrations are now 70% higher. The radioactive, radiochemical, chemical and microbiological criteria were examinated for sup(99m) Tc solutions. Like old generators, automatic generators were considered safe for medical purpose. (Author) [pt

  14. Long-Term Use of Everolimus in Patients with Tuberous Sclerosis Complex: Final Results from the EXIST-1 Study.

    Directory of Open Access Journals (Sweden)

    David N Franz

    Full Text Available Everolimus, a mammalian target of rapamycin (mTOR inhibitor, has demonstrated efficacy in treating subependymal giant cell astrocytomas (SEGAs and other manifestations of tuberous sclerosis complex (TSC. However, long-term use of mTOR inhibitors might be necessary. This analysis explored long-term efficacy and safety of everolimus from the conclusion of the EXIST-1 study (NCT00789828.EXIST-1 was an international, prospective, double-blind, placebo-controlled phase 3 trial examining everolimus in patients with new or growing TSC-related SEGA. After a double-blind core phase, all remaining patients could receive everolimus in a long-term, open-label extension. Everolimus was initiated at a dose (4.5 mg/m2/day titrated to a target blood trough of 5-15 ng/mL. SEGA response rate (primary end point was defined as the proportion of patients achieving confirmed ≥50% reduction in the sum volume of target SEGA lesions from baseline in the absence of worsening nontarget SEGA lesions, new target SEGA lesions, and new or worsening hydrocephalus. Of 111 patients (median age, 9.5 years who received ≥1 dose of everolimus (median duration, 47.1 months, 57.7% (95% confidence interval [CI], 47.9-67.0 achieved SEGA response. Of 41 patients with target renal angiomyolipomas at baseline, 30 (73.2% achieved renal angiomyolipoma response. In 105 patients with ≥1 skin lesion at baseline, skin lesion response rate was 58.1%. Incidence of adverse events (AEs was comparable with that of previous reports, and occurrence of emergent AEs generally decreased over time. The most common AEs (≥30% incidence suspected to be treatment-related were stomatitis (43.2% and mouth ulceration (32.4%.Everolimus use led to sustained reduction in tumor volume, and new responses were observed for SEGA and renal angiomyolipoma from the blinded core phase of the study. These findings support the hypothesis that everolimus can safely reverse multisystem manifestations of TSC in a

  15. Acute ST-Elevation Myocardial Infarction after Coronary Stent Fracture.

    Science.gov (United States)

    Rafighdust, Abbasali; Eshraghi, Ali

    2015-10-27

    The invention of the drug-eluting stent (DES) has brought about revolutionary changes in the field of interventional cardiology. In the DES era, in-stent restenosis has declined but new issues such as stent thrombosis have emerged. One of the emerging paradigms in the DES era is stent fracture. There are reports about stent fracture leading to in-stent restenosis or stent thrombosis. Most of these reports concern the Sirolimus-eluting stent. The present case is a representation of a Biolimus-eluting stent fracture. We introduce a 64-year-old male patient, for whom the BioMatrix stent was deployed in the right coronary artery. Five months after the implantation, he experienced acute myocardial infarction, with stent fracture leading to stent thrombosis being the causative mechanism. Another DES (Cypher) was used to manage this situation, and the final result was good.

  16. Everolimus immunosuppression reduces the serum expression of fibrosis markers in liver transplant recipients.

    Science.gov (United States)

    Fernández-Yunquera, Ainhoa; Ripoll, Cristina; Bañares, Rafael; Puerto, Marta; Rincón, Diego; Yepes, Ismael; Catalina, Vega; Salcedo, Magdalena

    2014-06-24

    To evaluate the expression of serum fibrosis markers in liver transplantation (LT) recipients on everolimus monotherapy compared to patients on an anti-calcineurin regimen. This cross-sectional case-control study included LT patients on everolimus monotherapy (cases) (E) (n = 30) and matched controls on an anti-calcineurin regimen (calcineurin inhibitors, CNI), paired by etiology of liver disease and time since LT (n = 30). Clinical characteristics, blood tests and elastography were collected. Serum levels of transforming growth factor-β (TGF-β), angiopoietin-1, tumor necrosis factor (TNF), platelet derived growth factor, amino-terminal propeptide of type III procollagen (PIIINP), hyaluronic acid (HA), VCM-1 (ng/mL), interleukin (IL)-10, interferon-inducible protein 10 (IP-10), vascular endothelial growth factor and hepatocyte growth factor (HGF) (pg/mL) were determined by enzyme-linked immunosorbent assay. Expression of these markers between E and CNI was compared. Stratified analysis was done according to factors that may influence liver fibrosis. Variables are described with medians (interquartillic range) or percentages. A total of 60 patients [age: 59 (49-64), hepatitis C virus (HCV): n = 21 (35%), time from LT: 73 mo (16-105)] were included. Patients had been on everolimus for a median of 15 mo. No differences in inflammatory activity, APRI test or liver elastography were found between the groups. No significant differences were observed between the groups in serum levels of PIIINP, metalloproteinase type = 1, angiopoietin, HGF, IP-10, TNF-α, IL-10 and vascular cell adhesion molecule. Patients on E had a lower expression of TGF-β [E: 12.7 (3.7-133.6), CNI: 152.5 (14.4-333.2), P = 0.009] and HA [E: 702.89 (329.4-838.2), CNI: 1513.6 (691.9-1951.4), P = 0.001] than those on CNI. This difference was maintained in the stratified analysis when recipient age is more than 50 years (TFG-β1: P = 0.06; HA: P = 0.005), in patients without active neoplasia (TFG-β1

  17. Impact of prior therapies on everolimus activity: an exploratory analysis of RADIANT-4

    Directory of Open Access Journals (Sweden)

    Buzzoni R

    2017-10-01

    Full Text Available Roberto Buzzoni,1 Carlo Carnaghi,2 Jonathan Strosberg,3 Nicola Fazio,4 Simron Singh,5 Fabian Herbst,6 Antonia Ridolfi,7 Marianne E Pavel,8 Edward M Wolin,9 Juan W Valle,10 Do-Youn Oh,11 James C Yao,12 Rodney Pommier13 1IRCCS Foundation, National Institute of Tumors, Milan, Italy; 2Humanitas Clinical and Research Center, Rozzano, Italy; 3Moffitt Cancer Center, Tampa, FL, USA; 4European Institute of Oncology, Milan, Italy; 5Sunnybrook Health Sciences Centre, Toronto, ON, Canada; 6Novartis AG, Basel, Switzerland; 7Novartis Pharma S.A.S., Rueil-Malmaison, France; 8Medizinische Klinik 1, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany; 9Montefiore Einstein Center for Cancer Care, Bronx, NY, USA; 10Institute of Cancer Sciences, University of Manchester, The Christie Hospital, Manchester, UK; 11Seoul National University Hospital, Seoul, Republic of Korea; 12University of Texas M.D. Anderson Cancer Center, Houston, TX, USA; 13Oregon Health & Science University, Portland, OR, USA Background: Recently, everolimus was shown to improve median progression-free survival (PFS by 7.1 months in patients with advanced, progressive, well-differentiated, nonfunctional neuroendocrine tumors (NET of lung or gastrointestinal (GI tract compared with placebo (HR, 0.48; 95% CI, 0.35–0.67; P<0.00001 in the Phase III, RADIANT-4 study. This post hoc analysis evaluates the impact of prior therapies (somatostatin analogs [SSA], chemotherapy, and radiotherapy on everolimus activity. Trial registration: ClinicalTrials.gov identifier: NCT01524783. Patients and methods: Patients were randomized (2:1 to everolimus 10 mg/day or placebo, both with best supportive care. Subgroups of patients who received prior SSA, chemotherapy, or radiotherapy (including peptide receptor radionuclide therapy were analyzed and reported. Results: A total of 302 patients were enrolled, of whom, 163 (54% had any prior SSA use (mostly for tumor control, 77 (25% received

  18. Porous Polymer Drug-Eluting Coating Prepared by Radiation Induced Polymerization

    International Nuclear Information System (INIS)

    Veres, M.; Beiler, B.; Himics, L.; Tóth, S.; Koós, M.

    2010-01-01

    Many areas of modern medicine are almost unimaginable without the use of different kinds of implants. They used as replacements, supports, auxiliary devices etc. for various parts or functions of the body. Their use has many advantages, however there could be some drawbacks too, like the possibility of rejection, inflammation and other side-effects. Many of these drawbacks are directly related to the materials used for the implant fabrication. Coatings are widely used to eliminate the unwanted effects appearing after the implantation. In addition to the protection and separation of tissues from the implant material they could also enhance the functionality and the acceptance of the artificial device and also promote the regeneration of the tissues after the intervention. Drug-eluting coatings are a good example for the latter. By delivery and controlled elution of drugs they could actively suppress inflammatory reactions, allergy and rejection of the implant, and their activity is localized to the place where these effects could mainly occur – to the region of the implant. This project is aimed to develop a drug-eluting porous polymer coating by radiation induced polymerization that can be used in different medical implants. The primary objects for this research are coronary stents however these porous layers could have perspective in other types of medical devices too. The main objectives are to develop a method for coating the surface of medical grade metallic alloy wires, plates and tubes with a porous polymer nanocomposite layer prepared by radiation induced polymerization and to characterize the obtained coatings

  19. Porous Polymer Drug-Eluting Coating Prepared by Radiation Induced Polymerization

    Energy Technology Data Exchange (ETDEWEB)

    Veres, M.; Beiler, B.; Himics, L.; Tóth, S.; Koós, M., E-mail: vm@szfki.hu [Hungarian Academy of Sciences, Research Institute for Solid State Physics and Optics, Department of Laser Applications, Konkoly Thege Miklós ut 29-33, 1121 Budapest, P.O. Box 49, 1525 Budapest (Hungary)

    2010-07-01

    Many areas of modern medicine are almost unimaginable without the use of different kinds of implants. They used as replacements, supports, auxiliary devices etc. for various parts or functions of the body. Their use has many advantages, however there could be some drawbacks too, like the possibility of rejection, inflammation and other side-effects. Many of these drawbacks are directly related to the materials used for the implant fabrication. Coatings are widely used to eliminate the unwanted effects appearing after the implantation. In addition to the protection and separation of tissues from the implant material they could also enhance the functionality and the acceptance of the artificial device and also promote the regeneration of the tissues after the intervention. Drug-eluting coatings are a good example for the latter. By delivery and controlled elution of drugs they could actively suppress inflammatory reactions, allergy and rejection of the implant, and their activity is localized to the place where these effects could mainly occur – to the region of the implant. This project is aimed to develop a drug-eluting porous polymer coating by radiation induced polymerization that can be used in different medical implants. The primary objects for this research are coronary stents however these porous layers could have perspective in other types of medical devices too. The main objectives are to develop a method for coating the surface of medical grade metallic alloy wires, plates and tubes with a porous polymer nanocomposite layer prepared by radiation induced polymerization and to characterize the obtained coatings.

  20. The combination of sorafenib and everolimus shows antitumor activity in preclinical models of malignant pleural mesothelioma

    International Nuclear Information System (INIS)

    Pignochino, Ymera; Dell’Aglio, Carmine; Inghilleri, Simona; Zorzetto, Michele; Basiricò, Marco; Capozzi, Federica; Canta, Marta; Piloni, Davide; Cemmi, Francesca; Sangiolo, Dario; Gammaitoni, Loretta; Soster, Marco; Marchiò, Serena; Pozzi, Ernesto; Morbini, Patrizia; Luisetti, Maurizio; Aglietta, Massimo; Grignani, Giovanni; Stella, Giulia M

    2015-01-01

    Malignant Pleural Mesothelioma (MPM) is an aggressive tumor arising from mesothelial cells lining the pleural cavities characterized by resistance to standard therapies. Most of the molecular steps responsible for pleural transformation remain unclear; however, several growth factor signaling cascades are known to be altered during MPM onset and progression. Transducers of these pathways, such as PIK3CA-mTOR-AKT, MAPK, and ezrin/radixin/moesin (ERM) could therefore be exploited as possible targets for pharmacological intervention. This study aimed to identify ‘druggable’ pathways in MPM and to formulate a targeted approach based on the use of commercially available molecules, such as the multikinase inhibitor sorafenib and the mTOR inhibitor everolimus. We planned a triple approach based on: i) analysis of immunophenotypes and mutational profiles in a cohort of thoracoscopic MPM samples, ii) in vitro pharmacological assays, ii) in vivo therapeutic approaches on MPM xenografts. No mutations were found in ‘hot spot’ regions of the mTOR upstream genes (e.g. EGFR, KRAS and PIK3CA). Phosphorylated mTOR and ERM were specifically overexpressed in the analyzed MPM samples. Sorafenib and everolimus combination was effective in mTOR and ERM blockade; exerted synergistic effects on the inhibition of MPM cell proliferation; triggered ROS production and consequent AMPK-p38 mediated-apoptosis. The antitumor activity was displayed when orally administered to MPM-bearing NOD/SCID mice. ERM and mTOR pathways are activated in MPM and ‘druggable’ by a combination of sorafenib and everolimus. Combination therapy is a promising therapeutic strategy against MPM. The online version of this article (doi:10.1186/s12885-015-1363-1) contains supplementary material, which is available to authorized users

  1. The Role Of Inflammation In Stent Restenosis More Than 1 Year Afetr Drug Eluting Stent Implantation

    Directory of Open Access Journals (Sweden)

    Hasan Shemirani

    2011-09-01

    Full Text Available Background: In stent restenosis (ISR following endovascular interventions is the main limitation of their long-term success. Despite advances have been made during recent years to decrease restenosis, it remains a challenging clinical problem.The aim of this study was to evaluate the relationship between angiographic coronary in stent restenosis, inflammation after successful stent implantation. Methods: This study included 78 patients, 35year old and higher who underwent coronary angiography more than 1 year after drug-eluting stent (DES implantation because of symptoms suggestive ischemia. Patients were divided into ISR group (case and patent stent group (control according to angiography results. For all patients blood lipids and high sensitivity C-Reactive Protein (hsCRP were measured simultaneously. Results: Age, sex, hypertension, current smoking, and lipid profile other than High Density Lipoprotein (HDL-C of patients in the case and control groups were similar .However, HDL-C < 40mg/L was more prevalent with ISR (66.7% vs. 30.8%, p=0.002. The hsCRP level was 2.98±2.06 mg/L in the case group and 2.50±1.80 mg/L in the control group. There were no significant differences in mean hsCRP concentration between the two groups (p=0.14, however mean hsCRP level was significantly higher in men of case group than control group (3.35mg/L vs. 2.21mg/L, p<0.05. Conclusion: This study demonstrates that in men but not in women inflammation may be a predictor of in stent restenosis more than 1 year after drug eluting stent implantation. Also, high-density lipoprotein (HDL probably has protective effect against stent restenosis.

  2. An acute episode of rhabdomyolysis associated with everolimus and cabergoline intake in a postpartum kidney recipient

    Directory of Open Access Journals (Sweden)

    B. I. Yaremin

    2017-01-01

    Full Text Available Kidney transplantation is one of the most promising ways to ensure the onset and successful maintenance of pregnancy in patients with end-stage chronic renal disease. A multicomponent drug therapy in such patients creates risks for fetal development, primarily due to the teratogenicity of mTOR receptor inhibitors and mycophenolate. Moreover, the inhibitors of the proliferative signal may have potential drug interactions, which can result in additional complications.Rhabdomyolysis is one of them. The paper describes the clinical case of an acute episode of reversible rhabdomyolysis in a patient on everolimus therapy.

  3. Everolimus-associated acute kidney injury in patients with metastatic breast cancer

    Directory of Open Access Journals (Sweden)

    A Chandra

    2017-01-01

    Full Text Available Recently, everolimus (Evl has been introduced in the management of hormone receptor-positive metastatic breast cancer, in combination with aromatase inhibitors. Evl-induced acute kidney injury has hitherto been described in other malignancies, especially renal cell cancer, but only once before in a patient with breast cancer. We describe two cases of Evl-associated nephrotoxicity in patients with breast cancer, one of whom underwent a renal biopsy showing acute tubular necrosis. Both our patients improved after withdrawal of the offending agent and have normal renal functions on follow-up.

  4. [Coronary stents: 30 years of medical progress].

    Science.gov (United States)

    Silvain, Johanne; Cayla, Guillaume; Collet, Jean-Philippe; Fargeot, Catherine; Montalescot, Gilles

    2014-03-01

    The history of interventional cardiology has been marked by several technologic revolutions since the late 1970s. The first key step was the use of inflatable balloon angioplasty as an alternative to CABG surgery for coronary revascularization, followed by intracoronary delivery of bare metal stent (BMS) and drug eluting stents (DES) to drastically reduce intracoronary restenosis observed with BMS. Improved stents platforms and polymers (absorbable or biocompatible) led to a dramatic reduction in the rate of late stent thrombosis. Self-expanding stents are now available to improve stent a position especially in acute myocardial infarction. The emergence of new fully bioabsorbable stents that can be combined with antiproliferative drugs is the ongoing revolution. A new generation of stents is continuously improving and likely to become the ideal stent for coronary revascularization in the near future. © 2014 médecine/sciences – Inserm.

  5. Dual-therapy stent technology for patients with coronary artery disease : A great catch?

    NARCIS (Netherlands)

    Kalkman, D.N.

    2018-01-01

    This thesis investigates the possible advantages of a new stent technology that aims to improve care for patients with coronary artery disease. The COMBO stent (OrbusNeich Medical BV, The Netherlands) contains a dual-therapy stent technology. The stent combines two techniques: a sirolimus-elution

  6. Co-occurrence of diabetes and hopelessness predicts adverse prognosis following percutaneous coronary intervention

    NARCIS (Netherlands)

    S.S. Pedersen (Susanne); J. Denollet (Johan); R.A.M. Erdman (Ruud); P.W.J.C. Serruys (Patrick); R.T. van Domburg (Ron)

    2009-01-01

    textabstractWe examined the impact of co-occurring diabetes and hopelessness on 3-year prognosis in percutaneous coronary intervention patients. Consecutive patients (n = 534) treated with the paclitaxel-eluting stent completed a set of questionnaires at baseline and were followed up for 3-year

  7. Cost-Effectiveness of Everolimus for Second-Line Treatment of Metastatic Renal Cell Carcinoma in Serbia

    NARCIS (Netherlands)

    Mihajlovic, Jovan; Pechlivanoglou, Petros; Sabo, Ana; Tomic, Zdenko; Postma, Maarten J.

    2013-01-01

    Background: New targeted therapeutics for metastatic renal cell carcinoma (mRCC) enable an increment in progression-free survival (PFS) ranging from 2 to 6 months. Compared with best supportive care, everolimus demonstrated an additional PFS of 3 months in patients with mRCC whose disease had

  8. Early conversion from calcineurin inhibitor- to everolimus-based therapy following kidney transplantation : Results of the randomized ELEVATE trial

    NARCIS (Netherlands)

    de Fijter, Johan W; Holdaas, Hallvard; Øyen, Ole; Sanders, Jan Stephan; Sundar, Sankaran; Bemelman, Frederike J; Sommerer, Claudia; Pascual, Julio; Avihingsanon, Yingyos; Pongskul, Cholatip; Oppenheimer, Frederic; Toselli, Lorenzo; Russ, Graeme; Wang, Zailong; Lopez, Patricia; Kochuparampil, Jossy; Cruzado, Josep M; van der Giet, Markus

    In a 24-month, multicenter, open-label, randomized trial, 715 de novo kidney transplant recipients were randomized at 10-14 weeks to convert to everolimus (n=359) or remain on standard calcineurin inhibitor (CNI) therapy (n=356; 231 tacrolimus; 125 cyclosporine), all with mycophenolic acid and

  9. Comparison of clinical outcomes after drug-eluting balloon and drug-eluting stent use for in-stent restenosis related acute myocardial infarction: a retrospective study

    Directory of Open Access Journals (Sweden)

    Chih-Yuan Fang

    2018-04-01

    Full Text Available Background Good results of drug-eluting balloon (DEB use are achieved in in-stent restenosis (ISR lesions, small vessel disease, long lesions, and bifurcations. However, few reports exist about DEB use in acute myocardial infarction (AMI with ISR. This study’s aim was to evaluate the efficacy of DEB for AMI with ISR. Methods Between November 2011 and December 2015, 117 consecutive patients experienced AMI including ST-segment elevation MI, and non-ST-segment elevation MI due to ISR, and received percutaneous coronary intervention (PCI. We divided our patients into two groups: (1 PCI with further DEB, and (2 PCI with further drug-eluting stent (DES. Clinical outcomes such as target lesion revascularization, target vessel revascularization, recurrent MI, stroke, cardiovascular mortality, and all-cause mortality were analyzed. Results The patients’ average age was 68.37 ± 11.41 years; 69.2% were male. A total of 75 patients were enrolled in the DEB group, and 42 patients were enrolled in the DES group. The baseline characteristics between the two groups were the same without statistical differences except for gender. Peak levels of cardiac biomarker, pre- and post-PCI cardiac function were similar between two groups. The major adverse cardiac cerebral events rate (34.0% vs. 35.7%; p = 0.688 and cardiovascular mortality rate (11.7% vs. 12.8%; p = 1.000 were similar in both groups. Conclusions DEB is a reasonable strategy for AMI with ISR. Compared with DES, DEB is an alternative strategy which yielded acceptable short-term outcomes and similar 1-year clinical outcomes.

  10. Production and setting of fractional elution facility for recovery of useful rare metals from seawater

    International Nuclear Information System (INIS)

    Seko, Noriaki; Kasai, Noboru; Tamada, Masao; Hasegawa, Shin; Katakai, Akio

    2005-01-01

    In September 1999, we have soaked 200 kg of fibrous amidoxime absorbents, synthesized by radiation-induced graft polymerization, into seawater to evaluate their performance. Fractional elution facility was set effectively to elute the rare metals on adsorbents in Mutsu-Establishment. This facility consists of two parts of pre-washing and elution. The present report dealt with planning, manufacture and setting of fractional facility. Marine organism and slime on adsorbent cassette (290 x 295 x 160 mm) were washed out and every 72 cassettes were set in elution unit (1210 x 1210 x H1460 mm) with nonwoven materials as a packing to avoid elution loss. In the elution process alkaline and alkaline earth metals were eluted with low concentration hydrochloric acid (0.01M) and rare metals were eluted with high concentration (0.5 M) after the packing of elution unit into fractional elution facility. Adsorbent cassettes were regenerated with alkaline solution after elution procedure. (author)

  11. Evaluation on elution feature of bentonite buffer materials

    Energy Technology Data Exchange (ETDEWEB)

    Ishikawa, Hirohisa; Kanno, Takeshi; Matsumoto, Kazuhiro

    1997-09-01

    In order to evaluate long term physical stability of artificial barrier in land disposal of high level radioactive wastes, it is necessary to know quantitatively elution behavior of buffering materials from disposal road (or cavity) to circumferential rock crack. When elution of the buffer material occurs on large scale, amount of bentonite in the disposal road (or cavity) reduces and reduction of various functions expected to the buffer materials is presumed. According to specification examples of road transverse arrangement and disposal vertical arrangement systems, evaluation on elution amount of the buffer materials at disposal environment was conducted. Opening width of rock crack in the disposal environment was supposed to be 0.5 mm. As a result, obtained mass elution ratios of the buffer materials due to extrusion phenomenon were 0.04 to 0.2% after 10,000 year and 2 to 12% after 1,000,000 years. (G.K.)

  12. Characterization of CRUDE OILS and petroleum products: (i) elution ...

    African Journals Online (AJOL)

    Characterization of CRUDE OILS and petroleum products: (i) elution liquid chromatographic separation and gas chromatographic analysis of crude oils and petroleum products. E.O. Odebunmi, E.A. Ogunsakin, P.E.P. Ilukhor ...

  13. Kuldkaru elutöö eest / Endel Link

    Index Scriptorium Estoniae

    Link, Endel

    2001-01-01

    Ameerika näitleja Kirk Douglas (1916), kellele seekordsel Berlinalel antakse elutöö eest Kuldkaru. Austamisõhtul näidatakse teda Stanley Kubricku kaua keelu all olnud filmis "Tee kuulsusele " ("Paths of Glory") : 1957

  14. Efficacy of palbociclib plus fulvestrant after everolimus in hormone receptor-positive metastatic breast cancer.

    Science.gov (United States)

    du Rusquec, Pauline; Palpacuer, Clément; Campion, Loic; Patsouris, Anne; Augereau, Paule; Gourmelon, Carole; Robert, Marie; Dumas, Laurence; Caroline, Folliard; Campone, Mario; Frenel, Jean-Sébastien

    2018-04-01

    Palbociclib, a CDK4-6 inhibitor, combined with endocrine therapy (ET) is a new standard of treatment for Hormone Receptor-positive Metastatic Breast Cancer. We present the first real-life efficacy and tolerance data of palbociclib plus fulvestrant in this population. From November 2015 to November 2016, patients receiving in our institution palbociclib + fulvestrant according to the Temporary Authorization for Use were prospectively analyzed. 60 patients were treated accordingly; median age was 61 years; 50 patients (83.3%) had visceral metastasis, and 10 (16.7%) had bone-only disease. Patients had previously received a median of 5 (1-14) lines of treatment, including ET (median 3) and chemotherapy (median 2); 28 (46.7%) received previously fulvestrant and all everolimus. With a median follow-up of 10.3 months, median progression-free survival (mPFS) was 5.8 months (95% CI 3.9-7.3). Patients pretreated with fulvestrant had a similar PFS of 6.4 months (HR 1.00; 95% CI 0.55-1.83; P = 1.00). The most common AEs (adverse events) were neutropenia (93%), anemia (65%), and thrombocytopenia (55%). In this heavily pretreated population including everolimus, fulvestrant plus palbociclib provides an mPFS of 5.8 months with the same magnitude of benefit for fulvestrant-pretreated patients.

  15. Composite outcomes in 2.25-mm drug eluting stents: a systematic review

    International Nuclear Information System (INIS)

    Lee, Justin Z.; Singh, Nirmal; Ortega, Gilbert; Low, See Wei; Kanakadandi, Uday; Fortuin, F. David; Lassar, Tom; Lee, Kwan S.

    2015-01-01

    Background: Coronary atherosclerosis often involves small-caliber coronaries, yet the safety and efficacy of 2.25-mm DES have been poorly defined, with a general lack of separation of 2.25 with 2.5-mm performance. No randomized head-to-head 2.25 mm DES studies have been reported. There are several single-arm prospective studies, and we aim to systematically review all published specific 2.25-mm data to estimate composite DES-specific performance and highlight current knowledge gaps. Methods: We performed a systematic literature search of PubMed, EMBASE, Web of Science and Cochrane database for clinical trials of 2.25-mm DES. Angiographic and composite clinical outcomes were compared with descriptive statistics. Results: 2.25 mm-Paclitaxel (PES), sirolimus (SES), everolimus (EES) and platinum chromium EES DES-specific outcomes have been reported. Death at 12 months for SES, PES, EES and platinum chromium EES was 1.3%, 3.0%, 1.5%, and 4.4%. Rates of target vessel revascularization at 12 months for SES, PES, EES and platinum chromium EES were 5.7%, 13.3%, 8.8%, and 3.3%. Angiographic outcomes at 9 months to one year were as follows: mean late lumen loss (LLL) for SES, PES, and EES was 0.15 ± 0.11-mm, 0.28 ± 0.11-mm, and 0.16 ± 0.41-mm and mean diameter restenosis for SES, PES, and EES were 29.5 ± 6.2%, 34.7 ± 4.2%, and 20.9 ± 22.5%. Reported stent thrombosis rates for 2.25-mm DES were low ranging from 0% to 2.2% in up to 24-months of follow-up. Conclusions: This systematic review summarizes and tabulates all available specific data on 2.25-mm DES. Based on our descriptive analysis, 2.25-mm DESs have a favorable safety and efficacy profile for the treatment of very small coronary lesions. - Highlights: • Safety and efficacy of 2.25-mm DES have been poorly defined. • We performed a systematic review on all published 2.25 mm data to estimate composite DES-specific performance and highlight current knowledge gaps. • We pooled data from 9 clinical studies and 1

  16. Composite outcomes in 2.25-mm drug eluting stents: a systematic review

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Justin Z. [Department of Medicine, University of Arizona, 1501 N Campbell Avenue, Tucson, AZ, 85724 (United States); Singh, Nirmal [Department of Cardiovascular Diseases, University of Arizona, 1501 N Campbell Ave, Tucson, AZ, 85724 (United States); Ortega, Gilbert [College of Medicine, University of Arizona, 1501 N Campbell Ave, Tucson, AZ, 85724 (United States); Low, See Wei; Kanakadandi, Uday [Department of Cardiovascular Diseases, University of Arizona, 1501 N Campbell Ave, Tucson, AZ, 85724 (United States); Fortuin, F. David [Department of Cardiovascular Diseases, Mayo Clinic Arizona, 5777 East Mayo Boulevard, Phoenix, AZ, 85054 (United States); Lassar, Tom [Department of Cardiovascular Diseases, University of Arizona, 1501 N Campbell Ave, Tucson, AZ, 85724 (United States); Lee, Kwan S., E-mail: klee@shc.arizona.edu [Department of Cardiovascular Diseases, University of Arizona, 1501 N Campbell Ave, Tucson, AZ, 85724 (United States)

    2015-06-15

    Background: Coronary atherosclerosis often involves small-caliber coronaries, yet the safety and efficacy of 2.25-mm DES have been poorly defined, with a general lack of separation of 2.25 with 2.5-mm performance. No randomized head-to-head 2.25 mm DES studies have been reported. There are several single-arm prospective studies, and we aim to systematically review all published specific 2.25-mm data to estimate composite DES-specific performance and highlight current knowledge gaps. Methods: We performed a systematic literature search of PubMed, EMBASE, Web of Science and Cochrane database for clinical trials of 2.25-mm DES. Angiographic and composite clinical outcomes were compared with descriptive statistics. Results: 2.25 mm-Paclitaxel (PES), sirolimus (SES), everolimus (EES) and platinum chromium EES DES-specific outcomes have been reported. Death at 12 months for SES, PES, EES and platinum chromium EES was 1.3%, 3.0%, 1.5%, and 4.4%. Rates of target vessel revascularization at 12 months for SES, PES, EES and platinum chromium EES were 5.7%, 13.3%, 8.8%, and 3.3%. Angiographic outcomes at 9 months to one year were as follows: mean late lumen loss (LLL) for SES, PES, and EES was 0.15 ± 0.11-mm, 0.28 ± 0.11-mm, and 0.16 ± 0.41-mm and mean diameter restenosis for SES, PES, and EES were 29.5 ± 6.2%, 34.7 ± 4.2%, and 20.9 ± 22.5%. Reported stent thrombosis rates for 2.25-mm DES were low ranging from 0% to 2.2% in up to 24-months of follow-up. Conclusions: This systematic review summarizes and tabulates all available specific data on 2.25-mm DES. Based on our descriptive analysis, 2.25-mm DESs have a favorable safety and efficacy profile for the treatment of very small coronary lesions. - Highlights: • Safety and efficacy of 2.25-mm DES have been poorly defined. • We performed a systematic review on all published 2.25 mm data to estimate composite DES-specific performance and highlight current knowledge gaps. • We pooled data from 9 clinical studies and 1

  17. Development of a sirolimus-eluting poly (L-lactide)/poly(4-hydroxybutyrate) absorbable stent for peripheral vascular intervention.

    Science.gov (United States)

    Grabow, Niels; Bünger, Carsten M; Kischkel, Sabine; Timmermann, J Hinrich; Reske, Thomas; Martin, David P; Williams, Simon F; Schareck, Wolfgang; Sternberg, Katrin; Schmitz, Klaus-Peter

    2013-10-01

    Fully absorbable drug-eluting stent platforms are currently entering the clinical arena for the interventional treatment of coronary artery disease. This new technology also holds potential for application in peripheral vascular settings. Our study reports on the development of a sirolimus- (SIR) eluting absorbable polymer stent made from a blend of poly(l-lactide) and poly(4-hydroxybutyrate) (PLLA/P4HB) for peripheral vascular intervention. Stent prototypes were laser-cut from PLLA/P4HB tubes (I.D.=2.2 mm, t=250 µm), spray-coated with different PLLA/P4HB/SIR solutions, and bench-tested to determine expansion properties, fatigue, trackability and in vitro drug release kinetics. The stent prototypes were expanded with a 5.0 × 20 mm balloon catheter, and exhibited a recoil of 3.6% upon balloon deflation. Stent collapse pressure of 0.4 bar (300 mm Hg) was measured under external pressure load. Sustained scaffolding properties were observed in vitro over 14 weeks of radial fatigue loading (50 ± 25 mm Hg at 1.2 Hz). Trackability was demonstrated in bench tests with an 8 French contralateral introducer sheath. SIR release kinetics were adjusted over a broad range by varying the PLLA/P4HB ratio of the coating matrix. The newly developed absorbable SIR-eluting PLLA/P4HB stent successfully fulfilled the requirements for peripheral vascular intervention under in vitro conditions.

  18. Nickel elution properties of contemporary interatrial shunt closure devices.

    Science.gov (United States)

    Verma, Divya Ratan; Khan, Muhammad F; Tandar, Anwar; Rajasekaran, Namakkal S; Neuharth, Renée; Patel, Amit N; Muhlestein, Joseph B; Badger, Rodney S

    2015-02-01

    We sought to compare nickel elution properties of contemporary interatrial shunt closure devices in vitro. There are two United States Food and Drug Administration (FDA)-approved devices for percutaneous closure of secundum atrial septal defect: the Amplatzer septal occluder (ASO; St Jude Medical Corporation) and Gore Helex septal occluder (HSO; W.L. Gore & Associates). The new Gore septal occluder (GSO) device is in clinical trials. These are also used off-label for patent foramen ovale closure in highly selected patients. These devices have high nickel content. Nickel allergy is the most common reason for surgical device explantation. Nickel elution properties of contemporary devices remain unknown. We compared nickel elution properties of 4 devices - ASO, GSO, HSO, and sternal wire (SW) - while Dulbecco's phosphate-buffered saline (DPBS) served as control. Three samples of each device were submerged in DPBS. Nickel content was measured at 14 intervals over 90 days. Nickel elution at 24 hours, compared to control (0.005 ± 0.0 mg/L), was significantly higher for ASO (2.98 ± 1.65 mg/L; P=.04) and SW (0.03 ± 0.014 mg/L; P=.03). Nickel levels at 90 days, compared to control (0.005 ± 0.0 mg/L) and adjusting for multiple comparisons, were significantly higher for ASO (19.80 ± 2.30 mg/L; P=.01) and similar for HSO (P=.34), GSO (P=.34), and SW (P=.34). ASO had significantly higher nickel elution compared to HSO, GSO, and SW (P=.01). There is substantial variability in nickel elution; devices with less exposed nickel (HSO and GSO) have minimal elution. The safety of low nickel elution devices in patients with nickel allergy needs to be evaluated in prospective trials.

  19. Phase II study of everolimus in children and adults with neurofibromatosis type 2 and progressive vestibular schwannomas

    Science.gov (United States)

    Karajannis, Matthias A.; Legault, Geneviève; Hagiwara, Mari; Giancotti, Filippo G.; Filatov, Alexander; Derman, Anna; Hochman, Tsivia; Goldberg, Judith D.; Vega, Emilio; Wisoff, Jeffrey H.; Golfinos, John G.; Merkelson, Amanda; Roland, J. Thomas; Allen, Jeffrey C.

    2014-01-01

    Background Activation of the mammalian target of rapamycin (mTOR) signaling pathway is thought to be a key driver of tumor growth in Merlin (NF2)-deficient tumors. Everolimus is an oral inhibitor of mTOR complex 1 (mTORC1) with antitumor activity in a variety of cancers. Methods We conducted a single-institution, prospective, 2-stage, open-label phase II study to estimate the response rate to everolimus in neurofibromatosis type 2 (NF2) patients with progressive vestibular schwannoma (VS). Ten eligible patients were enrolled, including 2 pediatric patients. Everolimus was administered at a daily dose of 10 mg (adults) or 5 mg/m2/day (children <18 y) orally in continuous 28-day courses, for up to 12 courses. Response was assessed every 3 months with MRI, using 3-dimensional volumetric tumor analysis, and audiograms. Nine patients were evaluable for the primary response, defined as ≥15% decrease in VS volume. Hearing response was evaluable as a secondary endpoint in 8 patients. Results None of the 9 patients with evaluable disease experienced a clinical or MRI response. No objective imaging or hearing responses were observed in stage 1 of the trial, and the study was closed according to predefined stopping rules. Conclusion Everolimus is ineffective for the treatment of progressive VS in NF2 patients. We are currently conducting a pharmacokinetic/pharmacodynamic (“phase 0”) study of everolimus in presurgical VS patients to elucidate the biological basis for apparent treatment resistance to mTORC1 inhibition in these tumors. PMID:24311643

  20. Next generation drug-eluting stents: focus on bioabsorbable platforms and polymers

    Directory of Open Access Journals (Sweden)

    Brendan Doyle

    2009-11-01

    Full Text Available Brendan Doyle, David R Holmes JrDivision of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota, USAAbstract: The success of drug-eluting stents in preventing restenosis has shifted the focus of new stent development toward enhancing long term safety and efficacy of these devices, while simultaneously eliminating the need for indefinite dual antiplatelet therapy. A technical advance fulfilling these aims would hold tremendous potential to reduce morbidity, mortality and economic costs associated with the percutaneous treatment of coronary artery disease. An attractive approach is the use of bioabsorbable stent designs. These may include stents with different bioabsorbable drugs, bioabsorbable polymers or even bioabsorbable metallic backbones. A device that could achieve excellent acute and long-term results, but disappear completely within months (thereby avoiding the need for prolonged dual antiplatelet therapy, would be a tremendous advance. Too good to be true? We explore here the scientific rationale and prospects for success with this exciting concept.Keywords: percutaneous coronary intervention, biodegradable, bioabsorbable, polymer, stent

  1. Two-year outcomes in thoracic transplant recipients after conversion to everolimus with reduced calcineurin inhibitor within a multicenter, open-label, randomized trial

    DEFF Research Database (Denmark)

    Gullestad, Lars; Mortensen, Svend-Aage; Eiskjær, Hans

    2010-01-01

    Use of the mammalian target of rapamycin inhibitor everolimus with an accompanying reduction in calcineurin inhibitor (CNI) exposure has shown promise in preserving renal function in maintenance thoracic transplant patients, but robust, long-term data are required....

  2. Dynamic tumor modeling of the dose–response relationship for everolimus in metastatic renal cell carcinoma using data from the phase 3 RECORD-1 trial

    International Nuclear Information System (INIS)

    Stein, Andrew; Wang, Wenping; Carter, Alison A; Chiparus, Ovidiu; Hollaender, Norbert; Kim, Hyewon; Motzer, Robert J; Sarr, Celine

    2012-01-01

    The phase 3 RECORD-1 trial (NCT00410124) established the efficacy and safety of everolimus in patients with metastatic renal cell carcinoma (mRCC) who progress on sunitinib or sorafenib. In RECORD-1, patients received 10 mg everolimus daily, with dose reduction to 5 mg daily allowed for toxicity. We have developed a model of tumor growth dynamics utilizing serial measurements of the sum of the longest tumor diameters (SLD) from individual RECORD-1 patients to define the dose–response relationship of everolimus. The model predicts that after 1 year of continuous dosing, the change in SLD of target lesions will be +142.1% ± 98.3%, +22.4% ± 17.2%, and –15.7% ± 11.5% in the average patient treated with placebo, 5 mg everolimus, and 10 mg everolimus, respectively. This nonlinear, mixed-effects modeling approach can be used to describe the dynamics of each individual patient, as well as the overall population. This allows evaluation of how an actual dosing history and individual covariates impact on the observed drug effect, and offers the possibility of predicting clinical observations as a function of time. In this pharmacodynamic model of tumor response, everolimus more effectively shrinks target lesions in mRCC when dosed 10 mg daily versus 5 mg daily, although a 5-mg dose still shows an antitumor effect. These data support earlier studies that established 10 mg daily as the preferred clinical dose of everolimus, and improve our understanding of the everolimus dose–response relationship

  3. CheckMate 025 Randomized Phase 3 Study: Outcomes by Key Baseline Factors and Prior Therapy for Nivolumab Versus Everolimus in Advanced Renal Cell Carcinoma.

    Science.gov (United States)

    Escudier, Bernard; Sharma, Padmanee; McDermott, David F; George, Saby; Hammers, Hans J; Srinivas, Sandhya; Tykodi, Scott S; Sosman, Jeffrey A; Procopio, Giuseppe; Plimack, Elizabeth R; Castellano, Daniel; Gurney, Howard; Donskov, Frede; Peltola, Katriina; Wagstaff, John; Gauler, Thomas C; Ueda, Takeshi; Zhao, Huanyu; Waxman, Ian M; Motzer, Robert J

    2017-12-01

    The randomized, phase 3 CheckMate 025 study of nivolumab (n=410) versus everolimus (n=411) in previously treated adults (75% male; 88% white) with advanced renal cell carcinoma (aRCC) demonstrated significantly improved overall survival (OS) and objective response rate (ORR). To investigate which baseline factors were associated with OS and ORR benefit with nivolumab versus everolimus. Subgroup OS analyses were performed using Kaplan-Meier methodology. Hazard ratios were estimated using the Cox proportional hazards model. Nivolumab 3mg/kg every 2 wk or everolimus 10mg once daily. The minimum follow-up was 14 mo. Baseline subgroup distributions were balanced between nivolumab and everolimus arms. Nivolumab demonstrated an OS improvement versus everolimus across subgroups, including Memorial Sloan Kettering Cancer Center (MSKCC) and International Metastatic Renal Cell Carcinoma Database Consortium risk groups; age guide treatment decisions, and further supports nivolumab as the standard of care in previously treated patients with aRCC. We investigated the impact of demographic and pretreatment features on survival benefit and tumor response with nivolumab versus everolimus in advanced renal cell carcinoma (aRCC). Survival benefit and response were observed for multiple subgroups, supporting the use of nivolumab as a new standard of care across a broad range of patients with previously treated aRCC. The trial is registered on ClinicalTrials.gov as NCT01668784. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  4. Coronary collaterals and risk for restenosis after percutaneous coronary interventions: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Meier Pascal

    2012-06-01

    Full Text Available Abstract Background The benefit of the coronary collateral circulation (natural bypass network on survival is well established. However, data derived from smaller studies indicates that coronary collaterals may increase the risk for restenosis after percutaneous coronary interventions. The purpose of this systematic review and meta-analysis of observational studies was to explore the impact of the collateral circulation on the risk for restenosis. Methods We searched the MEDLINE, EMBASE and ISI Web of Science databases (2001 to 15 July 2011. Random effects models were used to calculate summary risk ratios (RR for restenosis. The primary endpoint was angiographic restenosis > 50%. Results A total of 7 studies enrolling 1,425 subjects were integrated in this analysis. On average across studies, the presence of a good collateralization was predictive for restenosis (risk ratio (RR 1.40 (95% CI 1.09 to 1.80; P = 0.009. This risk ratio was consistent in the subgroup analyses where collateralization was assessed with intracoronary pressure measurements (RR 1.37 (95% CI 1.03 to 1.83; P = 0.038 versus visual assessment (RR 1.41 (95% CI 1.00 to 1.99; P = 0.049. For the subgroup of patients with stable coronary artery disease (CAD, the RR for restenosis with 'good collaterals' was 1.64 (95% CI 1.14 to 2.35 compared to 'poor collaterals' (P = 0.008. For patients with acute myocardial infarction, however, the RR for restenosis with 'good collateralization' was only 1.23 (95% CI 0.89 to 1.69; P = 0.212. Conclusions The risk of restenosis after percutaneous coronary intervention (PCI is increased in patients with good coronary collateralization. Assessment of the coronary collateral circulation before PCI may be useful for risk stratification and for the choice of antiproliferative measures (drug-eluting stent instead bare-metal stent, cilostazol.

  5. Investigation of the elution by seawater of caesium and strontium from loaded clinoptilolite

    International Nuclear Information System (INIS)

    Harder, B.R.; Mitchell, I.H.; Smyth, M.J.

    1985-07-01

    Simple investigations of the elution of caesium and strontium from loaded clinoptilolite are described. The clinoptilolite was loaded to levels expected in the British Nuclear Fuels plc SIXEP plant and contacted with seawater at approx. 15 C. (The elution time was measured until about 99% of the caesium and strontium had been eluted.) It was found that 99% of the caesium was eluted in 35 hours but the strontium (with more variable results) took at least 400 hours for 99% elution. (author)

  6. Coronary artery bypass grafting versus percutaneous intervention in coronary revascularization: a historical perspective and review

    Directory of Open Access Journals (Sweden)

    Burgess SN

    2015-06-01

    Full Text Available Sonya N Burgess,1 John J Edmond,2 Craig P Juergens,1 John K French11Department of Cardiology, Liverpool Hospital and South Western Sydney Clinical School, The University of New South Wales, Sydney, NSW, Australia; 2Department of Cardiology, Dunedin Public Hospital, Dunedin, New Zealand Background: Coronary artery bypass graft surgery is arguably the most intensively studied surgical procedure, and percutaneous coronary intervention (PCI has been subjected to more randomized clinical trials than any other interventional procedure. Changes seen in revascularization techniques have been numerous. The rapid evolution of evidence-based revascularization procedures has occurred as a result of many pivotal large randomized clinical trials. Objective: This review compares and contrasts outcomes from two coronary revascularization techniques, coronary artery bypass grafting (CABG and PCI, with particular reference to the landmark trials that inform practice guidelines. Methods: We undertook a comprehensive review of published literature addressing trials in this field performed to address current knowledge both in the predrug-eluting stent and postdrug-eluting stent era. Results and discussion: Surgical and percutaneous revascularization strategies have different strengths and weaknesses, and neither strategy is superior in all patients, clinical presentations, or anatomical subgroups. Current data support the use of percutaneous intervention in ST elevation myocardial infarction and in single-vessel disease. In noncomplex multivessel disease and isolated left main stem PCI, the data support non-inferiority of PCI compared to CABG as reflected in the 2014 European Society of Cardiology guidelines. Landmark revascularization trials of multivessel disease comparing CABG to PCI found no survival benefit to CABG over PCI, except in patients with complex disease. In these trials, revascularization drove differences in primary endpoints and in all but the

  7. Integral diagnosis of coronary atherosclerosis by coronary multidetector computed tomography and by invasive coronary angiography

    International Nuclear Information System (INIS)

    Llerena Rojas, Luis Roberto; Llerena Rojas, Lorenzo D; Mendoza Rodriguez, Vladimir

    2013-01-01

    Coronary angiography by multidetector computed tomography (CMDCT) visualizes the wall and lumen of coronary arteries. Invasive coronary angiography (INVCA) only visualizes the arterial lumen but with better resolution

  8. Ganciclovir-Resistant Cytomegalovirus Infection in a Kidney Transplant Recipient Successfully Treated with Foscarnet and Everolimus.

    Science.gov (United States)

    Menghi, Viola; Comai, Giorgia; Baraldi, Olga; Liviano D'Arcangelo, Giovanni; Lazzarotto, Tiziana; La Manna, Gaetano

    2016-01-01

    Cytomegalovirus (CMV) infection remains a major cause of morbidity, graft failure, and death in kidney transplant recipients. We describe a case of a 53-year-old CMV-seronegative man who underwent renal transplant from a CMV-positive donor and who developed ganciclovir- (GCV-) resistant CMV infection. Foscarnet was started while immunosuppressive therapy was modified with the introduction of everolimus minimizing tacrolimus dosage. Only two weeks after the start of this treatment regimen was the patient's viral load negative. At two-year follow-up the patient has no clinical or laboratory signs of CMV infection and a good and stable renal function or graft survival. In our case, administration of an mTOR inhibitor combined with foscarnet led to rapid and persistent viral clearance without compromising short- and medium-term graft function. This combination therapy supports the need for the kidney transplant community to individualize a target therapy for each type of GCV-resistant CMV infection.

  9. Influence of CYP3A5 genetic variation on everolimus maintenance dosing after cardiac transplantation.

    Science.gov (United States)

    Lesche, Dorothea; Sigurdardottir, Vilborg; Setoud, Raschid; Englberger, Lars; Fiedler, Georg M; Largiadèr, Carlo R; Mohacsi, Paul; Sistonen, Johanna

    2015-12-01

    Everolimus (ERL) has become an alternative to calcineurin inhibitors (CNIs) due to its renal-sparing properties, especially in heart transplant (HTx) recipients with kidney dysfunction. However, ERL dosing is challenging due to its narrow therapeutic window combined with high interindividual pharmacokinetic variability. Our aim was to evaluate the effect of clinical and genetic factors on ERL dosing in a pilot cohort of 37 HTx recipients. Variants in CYP3A5, CYP3A4, CYP2C8, POR, NR1I2, and ABCB1 were genotyped, and clinical data were retrieved from patient charts. While ERL trough concentration (C0 ) was within the targeted range for most patients, over 30-fold variability in the dose-adjusted ERL C0 was observed. Regression analysis revealed a significant effect of the non-functional CYP3A5*3 variant on the dose-adjusted ERL C0 (p = 0.031). ERL dose requirement was 0.02 mg/kg/d higher in patients with CYP3A5*1/*3 genotype compared to patients with CYP3A5*3/*3 to reach the targeted C0 (p = 0.041). ERL therapy substantially improved estimated glomerular filtration rate (28.6 ± 6.6 mL/min/1.73 m(2)) in patients with baseline kidney dysfunction. Everolimus pharmacokinetics in HTx recipients is highly variable. Our preliminary data on patients on a CNI-free therapy regimen suggest that CYP3A5 genetic variation may contribute to this variability. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Efficacy of everolimus in ABO-incompatible kidney transplantation: a retrospective study

    Directory of Open Access Journals (Sweden)

    Tsujimura K

    2017-09-01

    Full Text Available Kazuma Tsujimura,1 Morihito Ota,1 Kiyoshi Chinen,1 Kiyomitsu Nagayama,2 Masato Oroku,2 Morikuni Nishihira,2 Yoshiki Shiohira,2 Kunitoshi Iseki,3 Hideki Ishida,4 Kazunari Tanabe4 1Department of Surgery, 2Department of Nephrology, 3Clinical Research Support Center, Tomishiro Central Hospital, Okinawa, Japan; 4Department of Urology, Tokyo Women’s Medical University, Tokyo, Japan Background: There are limited reports on the use of everolimus for maintaining immunosuppression in ABO-incompatible (ABOi kidney transplantation (KT. As everolimus (EVR is effective for preventing calcineurin inhibitor (CNI nephrotoxicity without increasing the risk of chronic rejection and viral infection, we aimed to assess the efficacy of EVR in ABOi KT.Patients and methods: We retrospectively studied 22 patients who underwent KT and received EVR. Patients in the ABOi KT group (n=7 were compared with those in the ABO-compatible kidney transplantation group (ABOc KT; n=15. We recorded the frequency of CNI nephrotoxicity, chronic rejection, and viral infection in the 2 groups.Results: CNI nephrotoxicity, chronic rejection, and viral infection occurred in the ABOi KT and ANOc KT groups at rates of 28.3% (2/7 patients and 13.3% (2/15 patients (P=0.388, 28.3% (2/7 patients and 26.7% (4/15 patients (P=0.926, and 14.3% (1/7 patients and 26.7% (4/15 patients (P=0.517, respectively.Conclusion: Administration of EVR is effective in preventing CNI nephrotoxicity after KT. The rate of CNI nephrotoxicity was lower in the ABOc KT group than in the ABOi KT group. The rate of chronic rejection and viral infection was comparable between the groups. This study was conducted in a small cohort of patients. Hence, further evaluation with large sample sizes is necessary in the future to confirm the outcomes. Keywords: blood group incompatibility, immunosuppression, kidney transplantation

  11. Similar five-year outcome with paclitaxel- and sirolimus-eluting coronary stents

    DEFF Research Database (Denmark)

    Bligaard, Niels; Thuesen, Leif; Saunamäki, Kari

    2014-01-01

    patients with ST-segment elevation myocardial infarction (STEMI), non-STEMI, stable or unstable angina pectoris were randomized to receive Cypher™ (n = 1.065) or Taxus™ (n = 1.033) stents and were followed for 5 years. RESULTS: The primary end-point; the composite of cardiac death, myocardial infarction...... and target vessel revascularization (major adverse cardiac event, MACE), occurred in 467 patients (22.3%); Cypher™ n = 222 (20.8%), Taxus™ n = 245 (23.7%), ns. Definite and probable stent thrombosis occurred in 107 patients (5.1%); Cypher™ n = 51 (4.8%), Taxus™ n = 56 (5.4%), ns. No statistically significant...

  12. High coronary calcium score and post-procedural CK-MB are noninvasive predictors of coronary stent restenosis

    Directory of Open Access Journals (Sweden)

    Lee JB

    2017-02-01

    Full Text Available Jae-Beom Lee,1 Yun-Seok Choi,2 Woo-Baek Chung,2 Ami Kwon,2 Chul-Soo Park,2 Man-Young Lee2 1Anyang Sam Hospital, 2Division of Cardiology, Department of Internal Medicine, Youido St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea Purpose: High coronary calcium score (CCS and post-procedural cardiac enzyme may be related with poor outcomes in patients with coronary stent implantation. Methods: A total of 1,072 patients (63.2% male, mean age: 61.7±10.3 years who underwent coronary multi-detect computed tomography at index procedure and follow-up coronary angiography (CAG after drug-eluting stent (DES were divided into two groups: those with and without target lesion revascularization (TLR; >50% reduction in luminal stent diameter or angina symptoms on follow-up CAG. The CCSs for predicting stent revascularization were elucidated. Results: There were no significant differences between the two groups with regard to risk factors. The initial CCS was significantly higher in the TLR group (1,102.4±743.7 vs 345.8±51.05, P=0.04. After adjustment of significant factors for TLR, only CCS and post-procedural creatine kinase MB form (CK-MB elevation were significant predictors of coronary artery TLR. Receiver operation curve revealed that >800 in CCS had 69% in sensitivity and 88% in specificity about predicting the TLR. Conclusion: High CCS with post-procedural CK-MB might be the useful predictors for TLR after DES implantation. Keywords: coronary restenosis, drug-eluting stents, calcium, creatine kinase

  13. Treatment strategies in the left main coronary artery disease associated with acute coronary syndromes

    Directory of Open Access Journals (Sweden)

    Ahmet Karabulut

    2015-10-01

    Full Text Available Significant left main coronary artery (LMCA stenosis is not rare and reported 3 to 10% of patients undergoing coronary angiography. Unprotected LMCA intervention is a still clinical challenge and surgery is still going to be a traditional management method in many cardiac centers. With a presentation of drug eluting stent (DES, extensive use of IVUS and skilled operators, number of such interventions increased rapidly which lead to change in recommendation in the guidelines regarding LMCA procedures in the stable angina (Class 2a recommendation for ostial and shaft lesion and class 2b recommendation for distal bifurcation lesion. However, there was not clear consensus about the management of unprotected LMCA lesion associated with acute myocardial infarction (MI with a LMCA culprit lesion itself or distinct culprit lesion of other major coronary arteries. Surgery could be preferred as an obligatory management strategy even in the high risk patients. With this review, we aimed to demonstrate treatment strategies of LMCA disease associated with acute coronary syndrome, particularly acute myocardial infarction (MI. In addition, we presented a short case series with LMCA lesion and ST elevated acute MI in which culprit lesion placed either in the left anterior descending artery or circumflex artery. We reviewed the current medical literature and propose simple algorithm for management.

  14. Virtual histology assessment of cardiac allograft vasculopathy following introduction of everolimus--results of a multicenter trial

    DEFF Research Database (Denmark)

    Arora, Stina Jørgensen; Erikstad, I; Ueland, T

    2012-01-01

    of cardiac allograft vasculopathy (CAV). Parallel measurement of a range of inflammatory markers was also performed. A similar rate of quantitative CAV progression was observed in the everolimus (n = 30) and standard CNI group (n = 48) (plaque index 1.9 ± 3.8% and 1.6 ± 3.9%, respectively; p = 0.65). However...... with time since HTx >5.1 years and was accompanied by a significant increase in levels of von Willebrand (vWF) factor (p = 0.04) and vascular cell adhesion molecule (VCAM) (p = 0.03). Conversion to everolimus and reduced CNI is associated with a significant increase in calcified and necrotic intimal...

  15. A Phase 1 Study of Everolimus + Weekly Cisplatin + Intensity Modulated Radiation Therapy in Head-and-Neck Cancer

    International Nuclear Information System (INIS)

    Fury, Matthew G.; Lee, Nancy Y.; Sherman, Eric; Ho, Alan L.; Rao, Shyam; Heguy, Adriana; Shen, Ronglai; Korte, Susan; Lisa, Donna; Ganly, Ian; Patel, Snehal; Wong, Richard J.; Shaha, Ashok; Shah, Jatin; Haque, Sofia; Katabi, Nora; Pfister, David G.

    2013-01-01

    Purpose: Elevated expression of eukaryotic protein synthesis initiation factor 4E (eIF4E) in histologically cancer-free margins of resected head and neck squamous cell carcinomas (HNSCCs) is mediated by mammalian target of rapamycin complex 1 (mTORC1) and has been associated with increased risk of disease recurrence. Preclinically, inhibition of mTORC1 with everolimus sensitizes cancer cells to cisplatin and radiation. Methods and Materials: This was single-institution phase 1 study to establish the maximum tolerated dose of daily everolimus given with fixed dose cisplatin (30 mg/m 2 weekly × 6) and concurrent intensity modulated radiation therapy for patients with locally and/or regionally advanced head-and-neck cancer. The study had a standard 3 + 3 dose-escalation design. Results: Tumor primary sites were oral cavity (4), salivary gland (4), oropharynx (2), nasopharynx (1), scalp (1), and neck node with occult primary (1). In 4 of 4 cases in which resected HNSCC surgical pathology specimens were available for immunohistochemistry, elevated expression of eIF4E was observed in the cancer-free margins. The most common grade ≥3 treatment-related adverse event was lymphopenia (92%), and dose-limiting toxicities (DLTs) were mucositis (n=2) and failure to thrive (n=1). With a median follow up of 19.4 months, 2 patients have experienced recurrent disease. The maximum tolerated dose was everolimus 5 mg/day. Conclusions: Head-and-neck cancer patients tolerated everolimus at therapeutic doses (5 mg/day) given with weekly cisplatin and intensity modulated radiation therapy. The regimen merits further evaluation, especially among patients who are status post resection of HNSCCs that harbor mTORC1-mediated activation of eIF4E in histologically negative surgical margins

  16. A Phase 1 Study of Everolimus + Weekly Cisplatin + Intensity Modulated Radiation Therapy in Head-and-Neck Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Fury, Matthew G. [Department of Medicine, Head and Neck Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Department of Medicine, Weill Cornell Medical College, New York, New York (United States); Lee, Nancy Y. [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Sherman, Eric; Ho, Alan L. [Department of Medicine, Head and Neck Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Department of Medicine, Weill Cornell Medical College, New York, New York (United States); Rao, Shyam [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Heguy, Adriana [Department of Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Shen, Ronglai [Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Korte, Susan; Lisa, Donna [Department of Medicine, Head and Neck Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Ganly, Ian; Patel, Snehal; Wong, Richard J.; Shaha, Ashok; Shah, Jatin [Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Haque, Sofia [Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Katabi, Nora [Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Pfister, David G. [Department of Medicine, Head and Neck Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Department of Medicine, Weill Cornell Medical College, New York, New York (United States)

    2013-11-01

    Purpose: Elevated expression of eukaryotic protein synthesis initiation factor 4E (eIF4E) in histologically cancer-free margins of resected head and neck squamous cell carcinomas (HNSCCs) is mediated by mammalian target of rapamycin complex 1 (mTORC1) and has been associated with increased risk of disease recurrence. Preclinically, inhibition of mTORC1 with everolimus sensitizes cancer cells to cisplatin and radiation. Methods and Materials: This was single-institution phase 1 study to establish the maximum tolerated dose of daily everolimus given with fixed dose cisplatin (30 mg/m{sup 2} weekly × 6) and concurrent intensity modulated radiation therapy for patients with locally and/or regionally advanced head-and-neck cancer. The study had a standard 3 + 3 dose-escalation design. Results: Tumor primary sites were oral cavity (4), salivary gland (4), oropharynx (2), nasopharynx (1), scalp (1), and neck node with occult primary (1). In 4 of 4 cases in which resected HNSCC surgical pathology specimens were available for immunohistochemistry, elevated expression of eIF4E was observed in the cancer-free margins. The most common grade ≥3 treatment-related adverse event was lymphopenia (92%), and dose-limiting toxicities (DLTs) were mucositis (n=2) and failure to thrive (n=1). With a median follow up of 19.4 months, 2 patients have experienced recurrent disease. The maximum tolerated dose was everolimus 5 mg/day. Conclusions: Head-and-neck cancer patients tolerated everolimus at therapeutic doses (5 mg/day) given with weekly cisplatin and intensity modulated radiation therapy. The regimen merits further evaluation, especially among patients who are status post resection of HNSCCs that harbor mTORC1-mediated activation of eIF4E in histologically negative surgical margins.

  17. Pooled analysis of menstrual irregularities from three major clinical studies evaluating everolimus for the treatment of tuberous sclerosis complex.

    Directory of Open Access Journals (Sweden)

    Steven Sparagana

    Full Text Available To determine the impact of everolimus on female fertility, including menstrual irregularities, secondary amenorrhea, and luteinizing and follicle stimulating hormone levels in female patients.A pooled analysis from 3 prospective studies consisting of a core phase (≥6 months and a long-term follow-up open-label extension.One phase 2 single-center and two phase 3 multicenter studies.Data were obtained from female participants, restricted to those between 10 and 55 years of age, during 1 of 3 of the described clinical trials of everolimus. Patients had received ≥ 1 dose of everolimus.Incidence of fertility events.A total of 43/112 patients (38.4% experienced at least 1 menstrual irregularity. The most common events were amenorrhea (24.1% and irregular menstruation (17.0%. Seven patients (6.3% experienced grade 3/4 amenorrhea. When only the longest duration period of amenorrhea for each patient was considered, the median duration was 291 days. Fifteen patients attained menarche during the treatment period in any of the pooled studies. The mean age of menarche for this group was 12.4 years, similar to that of patients who were postmenarche at study entry (12.2 years. A total of 19/92 patients (20.7% who were postmenarche at baseline or during the study experienced an irregular menstruation event. An increased luteinizing hormone level was reported as an adverse event in 3/112 patients (3%, and follicle-stimulating hormone levels were within normal limits for these patients.No new safety concerns emerged regarding endocrine function and menstruation in female patients with tuberous sclerosis complex-associated subependymal giant cell astrocytoma or angiomyolipoma, who were receiving everolimus.ClinicalTrials.gov NCT00411619, NCT00789828, NCT00790400.

  18. Negative and positive affect are independently associated with patient-reported health status following percutaneous coronary intervention

    NARCIS (Netherlands)

    H. Versteeg (Henneke); S.S. Pedersen (Susanne); R.A.M. Erdman (Ruud); J.W.I. van Nierop; P.P.T. de Jaegere (Peter); R.T. van Domburg (Ron)

    2009-01-01

    textabstractPurpose: We examined the association between negative and positive affect and 12-month health status in patients treated with percutaneous coronary intervention (PCI) with drug-eluting stents. Methods: Consecutive PCI patients (n = 562) completed the Global Mood Scale at baseline to

  19. The effect of everolimus on renal angiomyolipoma in pediatric patients with tuberous sclerosis being treated for subependymal giant cell astrocytoma.

    Science.gov (United States)

    Bissler, John J; Franz, David N; Frost, Michael D; Belousova, Elena; Bebin, E Martina; Sparagana, Steven; Berkowitz, Noah; Ridolfi, Antonia; Kingswood, J Christopher

    2018-01-01

    Patients with tuberous sclerosis complex (TSC) often have multiple TSC-associated hamartomas, particularly in the brain and kidney. This was a post hoc analysis of pediatric patients being treated for subependymal giant cell astrocytomas (SEGAs) during the phase 3, randomized, double-blind, placebo-controlled EXIST-1 trial. Patients were initially randomly assigned to receive everolimus 4.5 mg/m 2 /day (target blood trough 5-15 mg/dl) or placebo and could continue in an open-label extension phase. Angiomyolipoma response rates were analyzed in patients aged 20% increase in kidney volume from nadir, and angiomyolipoma-related bleeding ≥ grade 2. Tolerability was also assessed. Overall, this analysis included 33 patients. Renal angiomyolipoma response was achieved by 75.8% of patients (95% confidence interval, 57.7-88.9%), with sustained mean reductions in renal angiomyolipoma volume over nearly 4 years of treatment. In addition, most (≥80%) achieved clinically relevant reductions in angiomyolipoma volume (≥50%), beginning at week 24 and continuing for the remainder of the study. Everolimus was generally well tolerated in this subgroup, with most adverse events being grade 1 or 2 in severity. Although everolimus is currently not indicated for this use, this analysis from EXIST-1 demonstrates its long-term efficacy and safety for the treatment of renal angiomyolipoma in pediatric patients undergoing treatment for TSC-associated SEGA.

  20. [Everolimus plus exemestane in postmenopausal patients with estrogen-receptor-positive advanced breast cancer - Japanese subgroup analysis of BOLERO -2].

    Science.gov (United States)

    Ito, Yoshinori; Masuda, Norikazu; Iwata, Hiroji; Mukai, Hirofumi; Horiguchi, Jun; Tokuda, Yutaka; Kuroi, Katsumasa; Mori, Asuka; Ohno, Nobutsugu; Noguchi, Shinzaburo

    2015-01-01

    In a phase 3, double-blind, randomized, international study (the BOLERO-2), the addition of mTOR inhibitor everolimus to exemestane was evaluated in postmenopausal women with estrogen-receptor-positive (ER⁺) advanced/recurrent breast cancer that was refractory to any nonsteroidal aromatase inhibitor (NSAI). This report presents the safety and updated (18- month) efficacy results from the Japanese subset (n=106) of BOLERO-2. After a median follow-up of 18 months, the median progression-free survival time was 8.5 months with everolimus plus exemestane compared to 4.2 months with placebo plus exemestane. The most common adverse events (AEs) with everolimus plus exemestane were stomatitis, rash, dysgeusia, and non-infectious lung disease. The AEs reported with the combination therapy were mostly of grade 1 or 2 and manageable with appropriate intervention. In conclusion, this combination could be a useful addition to the armamentarium of treatments for Japanese postmenopausal women with ER⁺ advanced/recurrent breast cancer progressing on NSAIs.

  1. Coronary heart disease

    Science.gov (United States)

    Heart disease, Coronary heart disease, Coronary artery disease; Arteriosclerotic heart disease; CHD; CAD ... buildup of plaque in the arteries to your heart. This may also be called hardening of the ...

  2. Current manufacturing processes of drug-eluting sutures.

    Science.gov (United States)

    Champeau, Mathilde; Thomassin, Jean-Michel; Tassaing, Thierry; Jérôme, Christine

    2017-11-01

    Drug-eluting sutures represent the next generation of surgical sutures since they fulfill their mechanical functions but also deliver the drug in their vicinity after implantation. These implants are produced by a variety of manufacturing processes. Drug-eluting sutures represent the next generation of surgical sutures since they fulfill their mechanical functions but also deliver the drug in their vicinity after implantation. These implants are produced by a variety of manufacturing processes. Two general approaches can be followed: (i) the ones that add the API into the material during the manufacturing process of the suture and (ii) the ones that load the API to an already manufactured suture. Areas covered: This review provides an overview of the current manufacturing processes for drug-eluting suture production and discusses their benefits and drawbacks depending on the type of drugs. The mechanical properties and the drug delivery profile of drug-eluting sutures are highlighted since these implants must fulfill both criteria. Expert opinion: For limited drug contents, melt extrusion and electrospinning are the emerging processes since the drug is added during the suture manufacture process. Advantageously, the drug release profile can be tuned by controlling the processing parameters specific to each process and the composition of the drug-containing polymer. If high drug content is targeted, the coating or grafting of a drug layer on a pre-manufactured suture allows for preservation of the tensile strength requirements of the suture.

  3. Development of a pheromone elution rate physical model

    Science.gov (United States)

    M.E. Teske; H.W. Thistle; B.L. Strom; H. Zhu

    2015-01-01

    A first principle modeling approach has been applied to available data describing the elution of semiochemicals from pheromone dispensers. These data included field data for 27 products developed by several manufacturers, including homemade devices, as well as environmental chamber data collected on three semiochemical products. The goal of this effort was to...

  4. Chronic Kidney Disease in the Second-Generation Drug-Eluting Stent Era: Pooled Analysis of the Korean Multicenter Drug-Eluting Stent Registry.

    Science.gov (United States)

    Lee, Joo Myung; Kang, Jeehoon; Lee, Euijae; Hwang, Doyeon; Rhee, Tae-Min; Park, Jonghanne; Kim, Hack-Lyoung; Lee, Sang Eun; Han, Jung-Kyu; Yang, Han-Mo; Park, Kyung Woo; Na, Sang-Hoon; Kang, Hyun-Jae; Koo, Bon-Kwon; Kim, Hyo-Soo

    2016-10-24

    The purpose of this study was to evaluate the clinical impact of chronic kidney disease (CKD) on clinical outcomes in contemporary practice of percutaneous coronary intervention (PCI) using second-generation drug-eluting stents (DES). Although second-generation DES have improved the safety and efficacy issues in PCI, data regarding the performance of second-generation DES in patients with CKD are still limited. We performed a patient-level pooled analysis on 12,426 patients undergoing PCI using second-generation DES from the Korean Multicenter Drug-Eluting Stent Registry. Endpoints were stent-oriented outcomes (target lesion failure [TLF]) and patient-oriented composite outcomes (POCO) during a median follow-up of 35 months. CKD patients were stratified by the estimated glomerular filtration rate (eGFR) from mild CKD to end-stage renal disease patients, and by the coexistence of diabetes mellitus (DM). A total of 2,927 patients had CKD (23.6%), who showed a significantly higher risk of TLF (adjusted hazard ratio [HR adjust ]: 1.50; 95% confidence interval [CI]: 1.21 to 1.86) and POCO (HR adjust 1.34; 95% CI: 1.17 to 1.55) compared to patients with preserved renal function. Stratified analysis by eGFR showed that TLF was not increased in the mild to moderate CKD, whereas severe CKD and dialysis-dependent patients showed significantly higher risk of TLF (HR adjust 2.44; 95% CI: 1.54 to 3.86; HR adjust 3.58; 95% CI: 2.52 to 5.08, respectively). The eGFR threshold of increased clinical events was 40 to 45 ml/min/1.73 m 2 . Among CKD patients, DM CKD patients showed a higher incidence of TLF compared to non-DM CKD patients (HR adjust : 1.82; 95% CI: 1.32 to 2.52), driven by the increase in target vessel-related events. In the era of second-generation DES, CKD patients were at a significantly higher risk of clinical outcomes only in severe CKD and end-stage renal disease patients. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All

  5. Everolimus and long acting octreotide as a volume reducing treatment of polycystic livers (ELATE: study protocol for a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Chrispijn Melissa

    2011-11-01

    Full Text Available Abstract Background Polycystic liver disease (PLD is defined as having more than 20 liver cysts and can present as a severe and disabling condition. Most symptoms are caused by the mass effect of the liver size and include abdominal pain and distension. The somatostatin analogues octreotide and lanreotide have proven to reduce polycystic liver volume. mTOR inhibitors such as everolimus inhibit cell proliferation and might thereby reduce growth of liver cysts. This trial aims to assess the benefit of combination therapy of everolimus and octreotide compared to octreotide monotherapy. In this study we present the structure of the trial and the characteristics of the included patients. Methods/design This is a randomized open-label clinical trial comparing the effect of 12 months of everolimus and octreotide to octreotide monotherapy in PLD patients. Primary outcome is change in liver volume determined by CT-volumetry. Secondary outcomes are changes in abdominal symptoms and quality of life. Moreover, safety and tolerability of the drugs will be assessed. Discussion This trial will compare the relative efficacy of combination therapy with octreotide and everolimus to octreotide monotherapy. Since they apply to different pathways of cystogenesis we expect that combining octreotide and everolimus will result in a cumulative reduction of polycystic liver volume. Trial registration number ClinicalTrials.gov: NCT01157858

  6. Phase 1 Trial of Everolimus and Radiation Therapy for Salvage Treatment of Biochemical Recurrence in Prostate Cancer Patients Following Prostatectomy

    International Nuclear Information System (INIS)

    Narayan, Vivek; Vapiwala, Neha; Mick, Rosemarie; Subramanian, Pearl; Christodouleas, John P.; Bekelman, Justin E.; Deville, Curtiland; Rajendran, Ramji; Haas, Naomi B.

    2017-01-01

    Purpose: In up to half of patients treated with salvage radiation therapy (SRT) for rising prostate-specific antigen levels, a second biochemical recurrence ultimately develops. Phosphatase and tensin homolog inactivation is implicated in prostate cancer progression, and upregulation of the mammalian target of rapamycin pathway can lead to tumor hypoxia and radioresistance. Everolimus is a mammalian target of rapamycin inhibitor with both antitumor and radiosensitizing effects. Methods and Materials: We performed a phase 1 study using a modified 3 + 3 dose-escalation design to evaluate the safety and tolerability of everolimus in combination with standard SRT for the treatment of biochemical recurrence following prostatectomy. After a 2-week run-in period of everolimus daily therapy, patients received prostate bed irradiation with daily cone beam computed tomography localization in 37 fractions of 1.8 Gy each (total dose, 66.6 Gy). Patients were monitored for both acute (≤90 days) and chronic (>90 days) treatment-related toxicities. Results: Eighteen patients received everolimus at dose levels of 5 mg (n=6), 7.5 mg (n=6), or 10 mg (n=6) daily in conjunction with SRT. No dose-limiting toxicities were observed. Common acute treatment-related toxicities included grade 1 or 2 mucositis (55.6%), grade 1 or 2 fatigue (38.9%), grade 1 or 2 rash (61.1%), and grade 1 urinary symptoms (61.1%). A grade 3 acute toxicity occurred in 4 patients (22.2%) (n=1 for rash, anemia, lymphopenia, and neutropenia), and no patients had a chronic toxicity of grade 3 or greater. After a median follow-up time of 17.8 months (range, 1.2-46.0 months), an undetectable prostate-specific antigen nadir was achieved in 9 patients (56.3%) and a second biochemical recurrence developed in 5 patients (31.3%). Conclusions: Everolimus at a dose of ≤10 mg daily appears to be safe and tolerable in combination with fractionated post-prostatectomy radiation therapy.

  7. Phase 1 Trial of Everolimus and Radiation Therapy for Salvage Treatment of Biochemical Recurrence in Prostate Cancer Patients Following Prostatectomy.

    Science.gov (United States)

    Narayan, Vivek; Vapiwala, Neha; Mick, Rosemarie; Subramanian, Pearl; Christodouleas, John P; Bekelman, Justin E; Deville, Curtiland; Rajendran, Ramji; Haas, Naomi B

    2017-02-01

    In up to half of patients treated with salvage radiation therapy (SRT) for rising prostate-specific antigen levels, a second biochemical recurrence ultimately develops. Phosphatase and tensin homolog inactivation is implicated in prostate cancer progression, and upregulation of the mammalian target of rapamycin pathway can lead to tumor hypoxia and radioresistance. Everolimus is a mammalian target of rapamycin inhibitor with both antitumor and radiosensitizing effects. We performed a phase 1 study using a modified 3 + 3 dose-escalation design to evaluate the safety and tolerability of everolimus in combination with standard SRT for the treatment of biochemical recurrence following prostatectomy. After a 2-week run-in period of everolimus daily therapy, patients received prostate bed irradiation with daily cone beam computed tomography localization in 37 fractions of 1.8 Gy each (total dose, 66.6 Gy). Patients were monitored for both acute (≤90 days) and chronic (>90 days) treatment-related toxicities. Eighteen patients received everolimus at dose levels of 5 mg (n=6), 7.5 mg (n=6), or 10 mg (n=6) daily in conjunction with SRT. No dose-limiting toxicities were observed. Common acute treatment-related toxicities included grade 1 or 2 mucositis (55.6%), grade 1 or 2 fatigue (38.9%), grade 1 or 2 rash (61.1%), and grade 1 urinary symptoms (61.1%). A grade 3 acute toxicity occurred in 4 patients (22.2%) (n=1 for rash, anemia, lymphopenia, and neutropenia), and no patients had a chronic toxicity of grade 3 or greater. After a median follow-up time of 17.8 months (range, 1.2-46.0 months), an undetectable prostate-specific antigen nadir was achieved in 9 patients (56.3%) and a second biochemical recurrence developed in 5 patients (31.3%). Everolimus at a dose of ≤10 mg daily appears to be safe and tolerable in combination with fractionated post-prostatectomy radiation therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Phase 1 Trial of Everolimus and Radiation Therapy for Salvage Treatment of Biochemical Recurrence in Prostate Cancer Patients Following Prostatectomy

    Energy Technology Data Exchange (ETDEWEB)

    Narayan, Vivek [Division of Hematology/Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Vapiwala, Neha [Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Mick, Rosemarie [Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Subramanian, Pearl [Division of Hematology/Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Christodouleas, John P.; Bekelman, Justin E.; Deville, Curtiland; Rajendran, Ramji [Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Haas, Naomi B., E-mail: naomi.haas@uphs.upenn.edu [Division of Hematology/Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania (United States)

    2017-02-01

    Purpose: In up to half of patients treated with salvage radiation therapy (SRT) for rising prostate-specific antigen levels, a second biochemical recurrence ultimately develops. Phosphatase and tensin homolog inactivation is implicated in prostate cancer progression, and upregulation of the mammalian target of rapamycin pathway can lead to tumor hypoxia and radioresistance. Everolimus is a mammalian target of rapamycin inhibitor with both antitumor and radiosensitizing effects. Methods and Materials: We performed a phase 1 study using a modified 3 + 3 dose-escalation design to evaluate the safety and tolerability of everolimus in combination with standard SRT for the treatment of biochemical recurrence following prostatectomy. After a 2-week run-in period of everolimus daily therapy, patients received prostate bed irradiation with daily cone beam computed tomography localization in 37 fractions of 1.8 Gy each (total dose, 66.6 Gy). Patients were monitored for both acute (≤90 days) and chronic (>90 days) treatment-related toxicities. Results: Eighteen patients received everolimus at dose levels of 5 mg (n=6), 7.5 mg (n=6), or 10 mg (n=6) daily in conjunction with SRT. No dose-limiting toxicities were observed. Common acute treatment-related toxicities included grade 1 or 2 mucositis (55.6%), grade 1 or 2 fatigue (38.9%), grade 1 or 2 rash (61.1%), and grade 1 urinary symptoms (61.1%). A grade 3 acute toxicity occurred in 4 patients (22.2%) (n=1 for rash, anemia, lymphopenia, and neutropenia), and no patients had a chronic toxicity of grade 3 or greater. After a median follow-up time of 17.8 months (range, 1.2-46.0 months), an undetectable prostate-specific antigen nadir was achieved in 9 patients (56.3%) and a second biochemical recurrence developed in 5 patients (31.3%). Conclusions: Everolimus at a dose of ≤10 mg daily appears to be safe and tolerable in combination with fractionated post-prostatectomy radiation therapy.

  9. The effect of stent coating on stent deliverability: direct randomised comparison of drug eluting and bare metal stents using the same stent platform.

    Science.gov (United States)

    Siminiak, Tomasz; Link, Rafał; Wołoszyn, Maciej; Kałmucki, Piotr; Baszko, Artur

    2012-01-01

    There is certain experimental and clinical evidence indicating that the covering of bare metal stents (BMS) with drug eluting polymers to produce drug eluting stents (DES) results in increased stent stiffness and modifies the mechanical properties of the stent platform. In addition, it has been speculated that the mechanical performance of DES, compared to BMS, may be related to the type of polymer used to cover stents. We aimed at evaluating the deliverability of DES with a lactate based biodegradable polymer and BMS in patients with stable coronary artery disease in a prospective randomised study. One hundred eleven consecutive patients (age: 36-77, mean 58.8 years) scheduled for routine angioplasty due to stable coronary disease were randomised to receive BMS (Chopin II(TM), Balton, Poland) or paclitaxel eluting stent (Chopin Luc(TM), Balton, Poland) using the same metal platform. Only patients scheduled for angioplasty using the direct implantation technique of a single stent were randomised. The exclusion criteria included patients 〉 80 years, multivessel disease and reference diameter of the target vessel 〉 3.5 mm. In the BMS group (n = 55; 35 males and 20 females), the mean diameter of implanted stents was 3.09 ± 0.40 and the mean length was 11.37 ± 2.80, whereas in the DES group (n = 56; 34 males and 22 females) the mean stent sizes were 3.02 ± 0.34 and 17.90 ± 7.38 mm, respectively (p 〉 0.05 for length). The groups did not significantly differ regarding the frequency of stent implantation to particular coronary vessels. The direct stenting technique was attempted and failed, leading to the stents' implantation after predilatation in five patients in the BMS group and six patients in the DES group. Failure of stent implantation and subsequent implantation of another stent type was observed in no BMS patients and in one DES patient (NS). Although stent covering with lactate based drug eluting polymer may increase its stiffness, it does not affect

  10. Bioresorbable scaffolds in the treatment of coronary artery disease

    Directory of Open Access Journals (Sweden)

    Zhang Y

    2013-03-01

    Full Text Available Yaojun Zhang,1,2 Christos V Bourantas,1 Vasim Farooq,1 Takashi Muramatsu,1 Roberto Diletti,1 Yoshinobu Onuma,1 Hector M Garcia-Garcia,1 Patrick W Serruys11Thoraxcenter, Erasmus Medical Center, Rotterdam, The Netherlands; 2Division of Cardiovascular Diseases, Nanjing First Hospital, Nanjing Medical University, Nanjing, People's Republic of ChinaAbstract: Drug-eluting stents have reduced the risk of in-stent restenosis and have broadened the application in percutaneous coronary intervention in coronary artery disease. However, the concept of using a permanent metallic endovascular device to restore the patency of a stenotic artery has inherited pitfalls, namely the presence of a foreign body within the artery causing vascular inflammation, late complications such as restenosis and stent thrombosis, and impeding the restoration of the physiologic function of the stented segment. Bioresorbable scaffolds (BRS were introduced to potentially overcome these limitations, as they provide temporary scaffolding and then disappear, liberating the treated vessel from its cage. Currently, several BRSs are available, undergoing evaluation either in clinical trials or in preclinical settings. The aim of this review is to present the new developments in BRS technology, describe the mechanisms involved in the resorption process, and discuss the potential future prospects of this innovative therapy.Keywords: bioresorbable scaffold, drug-eluting stent, biodegradable, design, mechanism, coronary artery disease

  11. Risk of stent thrombosis among bare-metal stents, first-generation drug-eluting stents, and second-generation drug-eluting stents: results from a registry of 18,334 patients.

    Science.gov (United States)

    Tada, Tomohisa; Byrne, Robert A; Simunovic, Iva; King, Lamin A; Cassese, Salvatore; Joner, Michael; Fusaro, Massimiliano; Schneider, Simon; Schulz, Stefanie; Ibrahim, Tareq; Ott, Ilka; Massberg, Steffen; Laugwitz, Karl-Ludwig; Kastrati, Adnan

    2013-12-01

    This study sought to compare the risk of stent thrombosis among patients treated with bare-metal stents (BMS), first-generation drug-eluting stents (G1-DES), and second-generation drug-eluting stents (G2-DES) for a period of 3 years. In patients undergoing coronary stenting, there is a scarcity of long-term follow-up data on cohorts large enough to compare rates of stent thrombosis across the stent generations. A total of 18,334 patients undergoing successful coronary stent implantation from 1998 to 2011 at 2 centers in Munich, Germany, were included in this study. Patients were stratified into 3 groups according to treatment with BMS, G1-DES, and G2-DES. The cumulative incidence of definite stent thrombosis at 3 years was 1.5% with BMS, 2.2% with G1-DES, and 1.0% with G2-DES. On multivariate analysis, G1-DES compared with BMS showed a significantly higher risk of stent thrombosis (odds ratio [OR]: 2.05; 95% confidence interval [CI]: 1.47 to 2.86; p stent thrombosis compared with BMS (OR: 0.82; 95% CI: 0.56 to 1.19; p = 0.30). Beyond 1 year, the risk of stent thrombosis was significantly increased with G1-DES compared with BMS (OR: 4.72; 95% CI: 2.01 to 11.1; p stenting, compared with BMS, there was a significant excess risk of stent thrombosis at 3 years with G1-DES, driven by an increased risk of stent thrombosis events beyond 1 year. G2-DES were associated with a similar risk of stent thrombosis compared with BMS. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  12. Magmaris: a new generation metallic sirolimus-eluting fully bioresorbable scaffold: present status and future perspectives.

    Science.gov (United States)

    Rapetto, Claudio; Leoncini, Massimo

    2017-08-01

    Drug-eluting stents (DES) have reached a high safety and efficacy profile, becoming the best option for percutaneous coronary interventions (PCI) based revascularization. However, despite their optimal performance, a few concerns remain regarding their use, mainly due to permanent caging of the vessels and its consequences, first of all late stent thrombosis (ST). Bioresorbable scaffolds (BRS) aim to overcome these issues. The results achieved in randomized controlled trials (RCT) by the first generation of poly-L-lactic acid (PLLA) based scaffolds were promising at 1 year, but the first long term reports (albeit flawed by non-optimal implantation technique) have been disappointing, showing, for instance, an increased risk of ST and target vessel myocardial infarction (TV-MI). In such a scenario the advent of a newer generation magnesium (Mg) based BRS is welcome, mainly because of its innovative mechanical and chemical features coupled with well proven biocompatibility. Despite being in its infancy, this technology seems to promise a great potential. In our article, we review the Magmaris (Biotronik AG, Bülach, Switzerland) Mg BRS development from animal models to human use, underscore its best qualities and weaknesses, and provide hints of its possible future perspectives.

  13. Factors that affect mass transport from drug eluting stents into the artery wall

    Directory of Open Access Journals (Sweden)

    Walsh Michael T

    2010-03-01

    Full Text Available Abstract Coronary artery disease can be treated by implanting a stent into the blocked region of an artery, thus enabling blood perfusion to distal vessels. Minimally invasive procedures of this nature often result in damage to the arterial tissue culminating in the re-blocking of the vessel. In an effort to alleviate this phenomenon, known as restenosis, drug eluting stents were developed. They are similar in composition to a bare metal stent but encompass a coating with therapeutic agents designed to reduce the overly aggressive healing response that contributes to restenosis. There are many variables that can influence the effectiveness of these therapeutic drugs being transported from the stent coating to and within the artery wall, many of which have been analysed and documented by researchers. However, the physical deformation of the artery substructure due to stent expansion, and its influence on a drugs ability to diffuse evenly within the artery wall have been lacking in published work to date. The paper highlights previous approaches adopted by researchers and proposes the addition of porous artery wall deformation to increase model accuracy.

  14. RTOG 0913: A Phase 1 Study of Daily Everolimus (RAD001) in Combination With Radiation Therapy and Temozolomide in Patients With Newly Diagnosed Glioblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Chinnaiyan, Prakash, E-mail: prakash.chinnaiyan@moffitt.org [Department of Radiation Oncology, Experimental Therapeutics and Cancer Imaging and Metabolism, H. Lee Moffitt Cancer Center, Tampa, Florida (United States); Won, Minhee [Radiation Therapy Oncology Group, Philadelphia, Pennsylvania (United States); Wen, Patrick Y. [Center for Neuro-Oncology, Dana-Farber/Brigham and Women' s Cancer Center, Boston, Massachusetts (United States); Rojiani, Amyn M. [Department of Pathology, Medical College of Georgia, Augusta, Georgia (United States); Wendland, Merideth [Radiation Oncology, US Oncology-Willamette Valley Cancer Institute, Eugene, Oregon (United States); Dipetrillo, Thomas A. [Department of Radiation Oncology, Rhode Island Hospital, Providence, Rhode Island (United States); Corn, Benjamin W. [Department of Radiation Oncology, Tel Aviv Medical Center, Tel Aviv (Israel); Mehta, Minesh P. [Department of Radiation Oncology, University of Maryland, Baltimore, Maryland (United States)

    2013-08-01

    Purpose: To determine the safety of the mammalian target of rapamycin inhibitor everolimus (RAD001) administered daily with concurrent radiation and temozolomide in newly diagnosed glioblastoma patients. Methods and Materials: Everolimus was administered daily with concurrent radiation (60 Gy in 30 fractions) and temozolomide (75 mg/m{sup 2} per day). Everolimus was escalated from 2.5 mg/d (dose level 1) to 5 mg/d (dose level 2) to 10 mg/d (dose level 3). Adjuvant temozolomide was delivered at 150 to 200 mg/m{sup 2} on days 1 to 5, every 28 days, for up to 12 cycles, with concurrent everolimus at the previously established daily dose of 10 mg/d. Dose escalation continued if a dose level produced dose-limiting toxicities (DLTs) in fewer than 3 of the first 6 evaluable patients. Results: Between October 28, 2010, and July 2, 2012, the Radiation Therapy Oncology Group 0913 protocol initially registered a total of 35 patients, with 25 patients successfully meeting enrollment criteria receiving the drug and evaluable for toxicity. Everolimus was successfully escalated to the predetermined maximum tolerated dose of 10 mg/d. Two of the first 6 eligible patients had a DLT at each dose level. DLTs included gait disturbance, febrile neutropenia, rash, fatigue, thrombocytopenia, hypoxia, ear pain, headache, and mucositis. Other common toxicities were grade 1 or 2 hypercholesterolemia and hypertriglyceridemia. At the time of analysis, there was 1 death reported, which was attributed to tumor progression. Conclusions: Daily oral everolimus (10 mg) combined with both concurrent radiation and temozolomide followed by adjuvant temozolomide is well tolerated, with an acceptable toxicity profile. A randomized phase 2 clinical trial with mandatory correlative biomarker analysis is currently under way, designed to both determine the efficacy of this regimen and identify molecular determinants of response.

  15. Budget impact analysis of everolimus for the treatment of hormone receptor positive, human epidermal growth factor receptor-2 negative (HER2-) advanced breast cancer in the United States.

    Science.gov (United States)

    Xie, Jipan; Diener, Melissa; De, Gourab; Yang, Hongbo; Wu, Eric Q; Namjoshi, Madhav

    2013-01-01

    To estimate the budget impact of everolimus as the first and second treatment option after letrozole or anastrozole (L/A) failure for post-menopausal women with hormone receptor positive (HR+), human epidermal growth factor receptor-2 negative (HER2-) advanced breast cancer (ABC). Pharmacy and medical budget impacts (2011 USD) were estimated over the first year of everolimus use in HR+, HER2- ABC from a US payer perspective. Epidemiology data were used to estimate target population size. Pre-everolimus entry treatment options included exemestane, fulvestrant, and tamoxifen. Pre- and post-everolimus entry market shares were estimated based on market research and assumptions. Drug costs were based on wholesale acquisition cost. Patients were assumed to be on treatment until progression or death. Annual medical costs were calculated as the average of pre- and post-progression medical costs weighted by the time in each period, adjusted for survival. One-way and two-way sensitivity analyses were conducted to assess the model robustness. In a hypothetical 1,000,000 member plan, 72 and 159 patients were expected to be candidates for everolimus treatment as first and second treatment option, respectively, after L/A failure. The total budget impact for the first year post-everolimus entry was $0.044 per member per month [PMPM] (pharmacy budget: $0.058 PMPM; medical budget: -$0.014 PMPM), assuming 10% of the target population would receive everolimus. The total budget impacts for the first and second treatment options after L/A failure were $0.014 PMPM (pharmacy budget: $0.018; medical budget: -$0.004) and $0.030 PMPM (pharmacy budget: $0.040; medical budget: -$0.010), respectively. Results remained robust in sensitivity analyses. Assumptions about some model input parameters were necessary and may impact results. Increased pharmacy costs for HR+, HER2- ABC following everolimus entry are expected to be partially offset by reduced medical service costs. Pharmacy and total

  16. A comprehensive review of everolimus clinical reports: a new mammalian target of rapamycin inhibitor.

    Science.gov (United States)

    Gurk-Turner, Cheryle; Manitpisitkul, Wana; Cooper, Matthew

    2012-10-15

    As new immunosuppressive agents are introduced to the market, clinicians are faced with the daunting task of sifting through the published literature to decide the value that the agent will add to their own practice. We often must extrapolate information provided through study in other solid-organ transplantation populations than our specific area of interest as we interpret the results and outcomes. With these challenges in mind, this compilation of published work for the newest mammalian target of rapamycin inhibitor everolimus (Certican; Novartis Pharmaceuticals, Hanover, NJ) (Zortress; Novartis Pharmaceuticals, Basel, Switzerland) is intended to provide a concise but thorough presentation of available literature so that the reader who may be unfamiliar with the agent can make their own judgment. Both Ovid and PubMed search engines were queried with a particular focus on high-impact articles noted in the Web of Science or Citation Index. Work described solely in abstract or case report form was excluded, as well as meta-analyses or those that were editorial or commentary in nature. Included were publications presented using the English language that described adult human subjects who received a heart, lung, kidney, or liver allograft. The goal of this strategy was to allow for the inclusion of pertinent literature in an unbiased fashion. Tables are provided that outline trial specific information, leaving a discussion of major outcomes to the text of the review.

  17. Bioabsorbable coronary stents--are these the next big thing in coronary angioplasty?

    Science.gov (United States)

    Balla, Sudarshan; Aggarwal, Kul; Nistala, Ravi

    2010-06-01

    The role of percutaneous coronary intervention (PCI) in the treatment of coronary artery disease has grown at an astronomical pace. Drug eluting stents (DES) offer advantages over bare metal stents (BMS) such as reduction in early in-stent restenosis rates. However, they have disadvantages like from increased late stent thrombosis when compared with BMS. Furthermore, recent data suggest endothelial dysfunction in the DES stented segments of the arteries. Currently, bioabsorbable stents are under development to avert the complications of DES such as stent thrombosis via degradation of the stent over time. The hypothetical advantage of leaving behind a natural vessel and restoring vasoreactivity may be the almost normal physiology which can be achieved after an intervention with a stent. The ABSORB and the PROGRESS AMS are two of the recent clinical trials that have looked at the outcomes of using bioabsorbable stents. So far, data from these and other studies has yielded mixed results in terms of angiographic and clinical outcomes. Newer stents such as REVA and WHISPER are presently being tested in preclinical and clinical trials. The landscape for bioabsorbable stents is constantly evolving through continued improvisation on existing technology and emergence of new technology. Large scale randomized trials are still needed with adequate long term follow-up for safety and benefits to have mainstream application in coronary artery disease, bioabsorbable stents are a promising innovation in the field of PCI. We review some of the patents and the data that is emerging on bioabsorbable stents in addition to currently ongoing clinical trials.

  18. [Drug-eluting stent thrombosis and its pharmacological prevention].

    Science.gov (United States)

    Pershukov, I V; Batyraliev, T A

    2007-01-01

    The problem of drug eluting stents (DES) safety has been actively discussed throughout 2006 because of increase of frequency of development of late stent thromboses which were noted during almost 2 years after stenting. In December 2006 US Food and Drug Administration (FDA) advisory panel acknowledged increase of development of late stent thrombosis. At the same time FDA accepted new definition of stent-thrombosis suggested by the Academic Research Consortium. According to this definition thrombosis can be definite, probable and possible. Any unexplained death before end of follow-up in a trial should be considered thrombosis related. Recalculation of thrombosis rate using this definition caused pronounced increase of this parameter in previously conducted trials. Thrombosis rate rose from 0,6 to 3,3% for bare metal stents, from 0,8 to 3,6% for sirolimus eluting stents and from 1,3 to 3,5% for paclitaxel eluting stents. Professional cardiological and angiographical societies (ACC, AHA, SCAI) responding to FDA advisory panel published their proofs and vision of the problem of stent thrombosis. In February 2007 ACC, AHA, SCAI, American College of Surgeons and Association of Dentists published scientific bulletin in which described preventive measures aimed at lowering of risk of thrombosis development. This document contains strict recommendation to continue double antithrombotic therapy with aspirin and clopidogrel for 12 months after implantation of DES or abandonment of the use of this type of stents when long term double antithrombotic therapy is not possible.

  19. Enhancing cognate target elution efficiency in gel-free chemical proteomics

    Directory of Open Access Journals (Sweden)

    Branka Radic-Sarikas

    2015-12-01

    Full Text Available Gel-free liquid chromatography mass spectrometry coupled to chemical proteomics is a powerful approach for characterizing cellular target profiles of small molecules. We have previously described a fast and efficient elution protocol; however, altered target profiles were observed. We hypothesised that elution conditions critically impact the effectiveness of disrupting drug-protein interactions. Thus, a number of elution conditions were systematically assessed with the aim of improving the recovery of all classes of proteins whilst maintaining compatibility with immunoblotting procedures. A double elution with formic acid combined with urea emerged as the most efficient and generically applicable elution method for chemical proteomics

  20. Interstitial Lung Disease Associated with mTOR Inhibitors in Solid Organ Transplant Recipients: Results from a Large Phase III Clinical Trial Program of Everolimus and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Patricia Lopez

    2014-01-01

    Full Text Available Interstitial lung disease (ILD has been reported with the use of mammalian target of rapamycin inhibitors (mTORi. The clinical and safety databases of three Phase III trials of everolimus in de novo kidney (A2309, heart (A2310, and liver (H2304 transplant recipients (TxR were searched using a standardized MedDRA query (SMQ search for ILD followed by a case-by-case medical evaluation. A literature search was conducted in MEDLINE and EMBASE. Out of the 1,473 de novo TxR receiving everolimus in Phase III trials, everolimus-related ILD was confirmed in six cases (one kidney, four heart, and one liver TxR representing an incidence of 0.4%. Everolimus was discontinued in three of the four heart TxR, resulting in ILD improvement or resolution. Outcome was fatal in the kidney TxR (in whom everolimus therapy was continued and in the liver TxR despite everolimus discontinuation. The literature review identified 57 publications on ILD in solid organ TxR receiving everolimus or sirolimus. ILD presented months or years after mTORi initiation and symptoms were nonspecific and insidious. The event was more frequent in patients with a late switch to mTORi. In most cases, ILD was reversed after prompt mTORi discontinuation. ILD induced by mTORi is an uncommon and potentially fatal event warranting early recognition and drug discontinuation.

  1. The mTOR kinase inhibitor Everolimus decreases S6 kinase phosphorylation but fails to reduce mutant huntingtin levels in brain and is not neuroprotective in the R6/2 mouse model of Huntington's disease

    Directory of Open Access Journals (Sweden)

    Frentzel Stefan

    2010-06-01

    Full Text Available Abstract Background Huntington's disease (HD is a progressive neurodegenerative disorder caused by a CAG repeat expansion within the huntingtin gene. Mutant huntingtin protein misfolds and accumulates within neurons where it mediates its toxic effects. Promoting mutant huntingtin clearance by activating macroautophagy is one approach for treating Huntington's disease (HD. In this study, we evaluated the mTOR kinase inhibitor and macroautophagy promoting drug everolimus in the R6/2 mouse model of HD. Results Everolimus decreased phosphorylation of the mTOR target protein S6 kinase indicating brain penetration. However, everolimus did not activate brain macroautophagy as measured by LC3B Western blot analysis. Everolimus protected against early declines in motor performance; however, we found no evidence for neuroprotection as determined by brain pathology. In muscle but not brain, everolimus significantly decreased soluble mutant huntingtin levels. Conclusions Our data suggests that beneficial behavioral effects of everolimus in R6/2 mice result primarily from effects on muscle. Even though everolimus significantly modulated its target brain S6 kinase, this did not decrease mutant huntingtin levels or provide neuroprotection.

  2. Ultra-hydrophilic stent platforms promote early vascular healing and minimise late tissue response: a potential alternative to second-generation drug-eluting stents.

    Science.gov (United States)

    Kolandaivelu, Kumaran; Bailey, Lynn; Buzzi, Stefano; Zucker, Arik; Milleret, Vincent; Ziogas, Algirdas; Ehrbar, Martin; Khattab, Ahmed A; Stanley, James R L; Wong, Gee K; Zani, Brett; Markham, Peter M; Tzafriri, Abraham R; Bhatt, Deepak L; Edelman, Elazer R

    2017-04-20

    Simple surface modifications can enhance coronary stent performance. Ultra-hydrophilic surface (UHS) treatment of contemporary bare metal stents (BMS) was assessed in vivo to verify whether such stents can provide long-term efficacy comparable to second-generation drug-eluting stents (DES) while promoting healing comparably to BMS. UHS-treated BMS, untreated BMS and corresponding DES were tested for three commercial platforms. A thirty-day and a 90-day porcine coronary model were used to characterise late tissue response. Three-day porcine coronary and seven-day rabbit iliac models were used for early healing assessment. In porcine coronary arteries, hydrophilic treatment reduced intimal hyperplasia relative to the BMS and corresponding DES platforms (1.5-fold to threefold reduction in 30-day angiographic and histological stenosis; p<0.04). Endothelialisation was similar on UHS-treated BMS and untreated BMS, both in swine and rabbit models, and lower on DES. Elevation in thrombotic indices was infrequent (never observed with UHS, rare with BMS, most often with DES), but, when present, correlated with reduced endothelialisation (p<0.01). Ultra-hydrophilic surface treatment of contemporary stents conferred good healing while moderating neointimal and thrombotic responses. Such surfaces may offer safe alternatives to DES, particularly when rapid healing and short dual antiplatelet therapy (DAPT) are crucial.

  3. Prevalence and impact of high platelet reactivity in chronic kidney disease: results from the Assessment of Dual Antiplatelet Therapy with Drug-Eluting Stents registry.

    Science.gov (United States)

    Baber, Usman; Mehran, Roxana; Kirtane, Ajay J; Gurbel, Paul A; Christodoulidis, Georgios; Maehara, Akiko; Witzenbichler, Bernhard; Weisz, Giora; Rinaldi, Michael J; Metzger, D Christopher; Henry, Timothy D; Cox, David A; Duffy, Peter L; Mazzaferri, Ernest L; Xu, Ke; Parise, Helen; Brodie, Bruce R; Stuckey, Thomas D; Stone, Gregg W

    2015-06-01

    Chronic kidney disease (CKD) is associated with increased rates of adverse events after percutaneous coronary intervention. We sought to determine the impact of CKD on platelet reactivity in clopidogrel-treated patients and whether high platelet reactivity (HPR) confers a similar or differential risk for adverse events among patients with CKD and non-CKD. We performed a post hoc analysis of the Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents (ADAPT-DES) registry, which included 8582 patients undergoing percutaneous coronary intervention with drug-eluting stents and platelet function testing using the VerifyNow assay. We compared HPR and its impact on ischemic and bleeding events >2 years among patients with CKD and non-CKD. Patients with CKD (n=1367) were older, more often female, diabetic, and had lower ejection fraction compared with their non-CKD counterparts (n=7043). Although HPR prevalence increased with worsening renal function in unadjusted analyses, these associations were no longer present after adjustment. Major adverse cardiac event rates at 2 years among those without CKD or HPR, HPR alone, CKD alone, and both CKD and HPR were 9.0%, 11.2%, 13.3%, and 17.5%, respectively (Pimpact of HPR on ischemic and bleeding events is similar irrespective of CKD status. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00638794. © 2015 American Heart Association, Inc.

  4. Coronary artery aneurysms

    Energy Technology Data Exchange (ETDEWEB)

    Koischwitz, D.; Harder, T.; Schuppan, U.; Thurn, P.

    1982-04-01

    Seven saccular coronary artery aneurysms have been demonstrated in the course of 1452 selective coronary artery angiograms. In six patients they were arterio-sclerotic; in one patient the aneurysm must have been congenital or of mycotic-embolic origin. The differential diagnosis between true aneurysms and other causes of vascular dilatation is discussed. Coronary artery aneurysms have a poor prognosis because of the possibility of rupture with resultant cardiac tamponade, or the development of thrombo-embolic myocardial infarction. These aneurysms can only be diagnosed by means of coronary angiography and require appropriate treatment.

  5. Indications for coronary angiography

    International Nuclear Information System (INIS)

    Kaltenbach, M.; Vallbracht, C.

    1985-01-01

    Today selective coronary angiography, introduced by Sones in 1957, is used as clinical routine for diagnosing morphological changes in the coronary arteries. Hitherto, more recent techniques such as digital subtraction angiography cannot provide comparable information. Strict criteria for its indication depending on possible therapeutic consequences, have to be applied, although the risk is low with a letality of 0.01 to 0.05 percent. Radionuclear investigations can be used as additional tool in selected cases. The careful indication for coronary angiography usually implies the possible need for coronary bypass graft surgery of balloon angioplasty. (orig./MG) [de

  6. A randomised comparison of novolimus-eluting and zotarolimus-eluting coronary stents: 9-Month follow-up results of the EXCELLA II study

    NARCIS (Netherlands)

    P.W.J.C. Serruys (Patrick); S.A. Garg (Scot); A.C. Abizaid (Alexandre); J.A. Ormiston (John); S.W. Windecker (Stephan); S. Verheye (Stefan); C. Dubois (Christophe); J. Stewart (J.); K. Hauptmann (Karl); J. Schofer (Joachim); K. Stangl (Karl); B. Witzenbichler (Bernhard); M. Wiemer (Marcus); E. Barbato (Emanuele); T. de Vries (Ton); A.-M. den Drijver (Anne-Marie); H. Otake (Hiromasa); L. Meredith (Lynn); S. Toyloy (Sara); P.J. Fitzgerald (Peter)

    2010-01-01

    textabstractAims: Novolimus, a macrocyclic lactone with anti-proliferative properties, has a similar efficacy to currently available agents; however it requires a lower dose, and less polymer, and is therefore conceivably safer. Methods and results: The EXCELLA II study was a prospective,

  7. Frequency of Cardiac Death and Stent Thrombosis in Patients With Chronic Obstructive Pulmonary Disease Undergoing Percutaneous Coronary Intervention (from the BASKET-PROVE I and II Trials)

    DEFF Research Database (Denmark)

    Jatene, Tannas; Biering-Sørensen, Tor; Nochioka, Kotaro

    2017-01-01

    Chronic obstructive pulmonary disease (COPD) is associated with long-term all-cause death after percutaneous coronary intervention with bare-metal stents. Regarding other outcomes, previous studies have shown conflicting results and the impact of drug-eluting stent (DES) in this population is not...

  8. Re-examining minimal luminal diameter relocation and quantitative coronary angiography - Intravascular ultrasound correlations in stented saphenous vein grafts: Methodological insights from the randomised RRISC trial

    NARCIS (Netherlands)

    O. Semeraro (Oscar); P. Agostoni (Pierfrancesco); S. Verheye (Stefan); G.J.J. van Langenhove (Glenn); P.A. van den Heuvel (Paul); C. Convens (Carl); F. van den Branden (Frank); N. Bruining (Nico); P. Vermeersch (Paul)

    2009-01-01

    textabstractAims: Angiographic parameters (such as late luminal loss) are common endpoints in drug-eluting stent trials, but their correlation with the neointimal process and their reliability in predicting restenosis are debated. Methods and results: Using quantitative coronary angiography (QCA)

  9. Recent perspective on coronary artery bifurcation interventions.

    Science.gov (United States)

    Dash, Debabrata

    2014-01-01

    Coronary bifurcation lesions are frequent in routine practice, accounting for 15-20% of all lesions undergoing percutaneous coronary intervention (PCI). PCI of this subset of lesions is technically challenging and historically has been associated with lower procedural success rates and worse clinical outcomes compared with non-bifurcation lesions. The introduction of drug-eluting stents has dramatically improved the outcomes. The provisional technique of implanting one stent in the main branch remains the default approach in most bifurcation lesions. Selection of the most effective technique for an individual bifurcation is important. The use of two-stent techniques as an intention to treat is an acceptable approach in some bifurcation lesions. However, a large amount of metal is generally left unapposed in the lumen with complex two-stent techniques, which is particularly concerning for the risk of stent thrombosis. New technology and dedicated bifurcation stents may overcome some of the limitations of two-stent techniques and revolutionise the management of bifurcation PCI in the future.

  10. Cost-effectiveness analysis of biodegradable polymer versus durable polymer drug-eluting stents incorporating real-world evidence.

    Science.gov (United States)

    Teng, Monica; Zhao, Ying Jiao; Khoo, Ai Leng; Ananthakrishna, Rajiv; Yeo, Tiong Cheng; Lim, Boon Peng; Chan, Mark Y; Loh, Joshua P

    2018-06-05

    Compared with second-generation durable polymer drug-eluting stents (DP-DES), the cost-effectiveness of biodegradable polymer drug-eluting stents (BP-DES) remains unclear in the real-world setting. We assessed the cost-effectiveness of BP-DES in patients with coronary artery disease undergoing percutaneous coronary intervention (PCI). We developed a decision-analytic model to compare the cost-effectiveness of BP-DES to DP-DES over one year and five years from healthcare payer perspective. Relative treatment effects during the first year post-PCI were obtained from a real-world population analysis while clinical event risks in the subsequent four years were derived from a meta-analysis of published studies. At one year, based on the clinical data analysis of 497 propensity-score matched pairs of patients, BP-DES were associated with an incremental cost-effectiveness ratio (ICER) of USD20,503 per quality-adjusted life-year (QALY) gained. At five years, BP-DES yielded an ICER of USD4,062 per QALY gained. At the willingness-to-pay threshold of USD50,400 (one gross domestic product per capita in Singapore in 2015), BP-DES were cost-effective. Sensitivity analysis showed that the cost of stents had a significant impact on the cost-effectiveness of BP-DES. Threshold analysis demonstrated that if the cost difference between BP-DES and DP-DES exceeded USD493, BP-DES would not be cost-effective in patients with one-year of follow-up. BP-DES were cost-effective compared with DP-DES in patients with coronary artery disease at one year and five years after PCI. It is worth noting that the cost of stents had a significant impact on the findings. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  11. The mTOR inhibitor, everolimus (RAD001), overcomes resistance to imatinib in quiescent Ph-positive acute lymphoblastic leukemia cells

    International Nuclear Information System (INIS)

    Kuwatsuka, Y; Minami, M; Minami, Y; Sugimoto, K; Hayakawa, F; Miyata, Y; Abe, A; Goff, D J; Kiyoi, H; Naoe, T

    2011-01-01

    In Ph-positive (Ph + ) leukemia, the quiescent cell state is one of the reasons for resistance to the BCR-ABL-kinase inhibitor, imatinib. In order to examine the mechanisms of resistance due to quiescence and the effect of the mammalian target of rapamycin inhibitor, everolimus, for such a resistant population, we used Ph + acute lymphoblastic leukemia patient cells serially xenotransplanted into NOD/SCID/IL2rγ null (NOG) mice. Spleen cells from leukemic mice showed a higher percentage of slow-cycling G 0 cells in the CD34 + CD38 − population compared with the CD34 + CD38 + and CD34 − populations. After ex vivo imatinib treatment, more residual cells were observed in the CD34 + CD38 − population than in the other populations. Although slow-cycling G 0 cells were insensitive to imatinib in spite of BCR-ABL and CrkL dephosphorylation, combination treatment with everolimus induced substantial cell death, including that of the CD34 + CD38 − population, with p70-S6 K dephosphorylation and decrease of MCL-1 expression. The leukemic non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mouse system with the in vivo combination treatment with imatinib and everolimus showed a decrease of tumor burden including CD34 + cells. These results imply that treatment with everolimus can overcome resistance to imatinib in Ph + leukemia due to quiescence

  12. Satisfactory arterial repair 1 year after ultrathin strut biodegradable polymer sirolimus-eluting stent implantation: an angioscopic observation.

    Science.gov (United States)

    Ishihara, Takayuki; Awata, Masaki; Iida, Osamu; Fujita, Masashi; Masuda, Masaharu; Okamoto, Shin; Nanto, Kiyonori; Kanda, Takashi; Tsujimura, Takuya; Uematsu, Masaaki; Mano, Toshiaki

    2018-01-15

    The ultrathin strut biodegradable polymer sirolimus-eluting stent (Orsiro, O-SES) exhibits satisfactory clinical outcomes. However, no report to date has documented the intravascular status of artery repair after O-SES implantation. We examined 5 O-SES placed in 4 patients (age 65 ± 12 years, male 75%) presenting with stable angina pectoris due to de novo lesions in native coronary arteries. Coronary angioscopy was performed immediately after percutaneous coronary intervention and 1 year later. Angioscopic images were analyzed to determine the following: (1) dominant grade of neointimal coverage (NIC) over the stent; (2) maximum yellow plaque grade; and (3) existence of thrombus. Yellow plaque grade was evaluated both immediately after stent implantation and at the time of follow-up observation. The other parameters were evaluated at the time of follow-up examination. NIC was graded as: grade 0, stent struts exposed; grade 1, struts bulging into the lumen, although covered; grade 2, struts embedded in the neointima, but translucent; grade 3, struts fully embedded and invisible. Yellow plaque severity was graded as: grade 0, white; grade 1, light yellow; grade 2, yellow; and grade 3, intensive yellow. Angioscopic findings at 1 year demonstrated the following: dominant NIC grade 1, grade 2, and grade 3 in 1, 2, and 2 stents, respectively; all stents were covered to some extent; focal thrombus adhesion was observed in only 1 stent. Yellow plaque grade did not change from immediately after stent implantation to follow-up. O-SES demonstrated satisfactory arterial repair 1 year after implantation.

  13. Optimization of Drug Delivery by Drug-Eluting Stents.

    Directory of Open Access Journals (Sweden)

    Franz Bozsak

    Full Text Available Drug-eluting stents (DES, which release anti-proliferative drugs into the arterial wall in a controlled manner, have drastically reduced the rate of in-stent restenosis and revolutionized the treatment of atherosclerosis. However, late stent thrombosis remains a safety concern in DES, mainly due to delayed healing of the endothelial wound inflicted during DES implantation. We present a framework to optimize DES design such that restenosis is inhibited without affecting the endothelial healing process. To this end, we have developed a computational model of fluid flow and drug transport in stented arteries and have used this model to establish a metric for quantifying DES performance. The model takes into account the multi-layered structure of the arterial wall and incorporates a reversible binding model to describe drug interaction with the cells of the arterial wall. The model is coupled to a novel optimization algorithm that allows identification of optimal DES designs. We show that optimizing the period of drug release from DES and the initial drug concentration within the coating has a drastic effect on DES performance. Paclitaxel-eluting stents perform optimally by releasing their drug either very rapidly (within a few hours or very slowly (over periods of several months up to one year at concentrations considerably lower than current DES. In contrast, sirolimus-eluting stents perform optimally only when drug release is slow. The results offer explanations for recent trends in the development of DES and demonstrate the potential for large improvements in DES design relative to the current state of commercial devices.

  14. Everolimus and sirolimus in combination with cyclosporine have different effects on renal metabolism in the rat.

    Directory of Open Access Journals (Sweden)

    Rahul Bohra

    Full Text Available Enhancement of calcineurin inhibitor nephrotoxicity by sirolimus (SRL is limiting the clinical use of this drug combination. We compared the dose-dependent effects of the structurally related everolimus (EVL and sirolimus (SRL alone, and in combination with cyclosporine (CsA, on the rat kidney. Lewis rats were treated by oral gavage for 28 days using a checkerboard dosing format (0, 3.0, 6.0 and 10.0 CsA and 0, 0.5, 1.5 and 3.0 mg/kg/day SRL or EVL, n = 4/dose combination. After 28 days, oxidative stress, energy charge, kidney histologies, glomerular filtration rates, and concentrations of the immunosuppressants were measured along with (1H-magnetic resonance spectroscopy (MRS and gas chromatography- mass spectrometry profiles of cellular metabolites in urine. The combination of CsA with SRL led to higher urinary glucose concentrations and decreased levels of urinary Krebs cycle metabolites when compared to controls, suggesting that CsA+SRL negatively impacted proximal tubule metabolism. Unsupervised principal component analysis of MRS spectra distinguished unique urine metabolite patterns of rats treated with CsA+SRL from those treated with CsA+EVL and the controls. SRL, but not EVL blood concentrations were inversely correlated with urine Krebs cycle metabolite concentrations. Interestingly, the higher the EVL concentration, the closer urine metabolite patterns resembled those of controls, while in contrast, the combination of the highest doses of CsA+SRL showed the most significant differences in metabolite patterns. Surprisingly in this rat model, EVL and SRL in combination with CsA had different effects on kidney biochemistry, suggesting that further exploration of EVL in combination with low dose calcineurin inhibitors may be of potential benefit.

  15. Coronary artery bypass surgery or coronary stenting in diabetic patients: too soon to make a statement?

    Energy Technology Data Exchange (ETDEWEB)

    Rodriguez, Alfredo E., E-mail: arodriguez@centroceci.com.ar

    2014-11-15

    Diabetic patients have been associated with poor procedural and long term outcome if they were treated either with percutaneous coronary interventions or coronary artery bypass surgery. Recently several randomized clinical trials (RCT) in this subset of patients have been published showing a greater incidence of major adverse cardiovascular events, death/myocardial infarction/stroke, if they were treated with first generation drug eluting stents (DES) which was not observed previously in the bare metal stent era. However, almost simultaneously with this data, several RCT demonstrated better safety profile with new generation DES including biocompatible polymers, biodegradable polymers and lately complete absorbable DES, all of them showed reduction in adverse cardiac events compared to 1st generation DES in patients with diabetes. In this editorial we review the old and new randomized data in diabetic patients and conclude that there are many unresolved issues to make a definitive statement regarding which is the best revascularization preference in diabetic patients and the measured final efficacy of PCI and CABG will not be reached until the arrival of RCT using next generation DES, including complete absorbable scaffolds. - Highlights: • Diabetic patients have been associated with poor procedural and long term outcome if they were treated either with percutaneous coronary interventions or coronary artery bypass surgery. Recently several randomized clinical trials (RCT) in this subset of patients have been published showing a greater incidence of major adverse cardiovascular events, death/myocardial infarction/stroke, if they were treated with first generation drug eluting stents (DES) which was not observed previously in the bare metal stent era. • In recent years, several RCT demonstrated better safety profile with new generation DES including biocompatible polymers, biodegradable polymers and lately complete absorbable DES, all of them showed reduction in

  16. Coronary artery bypass surgery or coronary stenting in diabetic patients: too soon to make a statement?

    International Nuclear Information System (INIS)

    Rodriguez, Alfredo E.

    2014-01-01

    Diabetic patients have been associated with poor procedural and long term outcome if they were treated either with percutaneous coronary interventions or coronary artery bypass surgery. Recently several randomized clinical trials (RCT) in this subset of patients have been published showing a greater incidence of major adverse cardiovascular events, death/myocardial infarction/stroke, if they were treated with first generation drug eluting stents (DES) which was not observed previously in the bare metal stent era. However, almost simultaneously with this data, several RCT demonstrated better safety profile with new generation DES including biocompatible polymers, biodegradable polymers and lately complete absorbable DES, all of them showed reduction in adverse cardiac events compared to 1st generation DES in patients with diabetes. In this editorial we review the old and new randomized data in diabetic patients and conclude that there are many unresolved issues to make a definitive statement regarding which is the best revascularization preference in diabetic patients and the measured final efficacy of PCI and CABG will not be reached until the arrival of RCT using next generation DES, including complete absorbable scaffolds. - Highlights: • Diabetic patients have been associated with poor procedural and long term outcome if they were treated either with percutaneous coronary interventions or coronary artery bypass surgery. Recently several randomized clinical trials (RCT) in this subset of patients have been published showing a greater incidence of major adverse cardiovascular events, death/myocardial infarction/stroke, if they were treated with first generation drug eluting stents (DES) which was not observed previously in the bare metal stent era. • In recent years, several RCT demonstrated better safety profile with new generation DES including biocompatible polymers, biodegradable polymers and lately complete absorbable DES, all of them showed reduction in

  17. Efficacy and safety of everolimus in combination with trastuzumab and paclitaxel in Asian patients with HER2+ advanced breast cancer in BOLERO-1.

    Science.gov (United States)

    Toi, Masakazu; Shao, Zhimin; Hurvitz, Sara; Tseng, Ling-Ming; Zhang, Qingyuan; Shen, Kunwei; Liu, Donggeng; Feng, Jifeng; Xu, Binghe; Wang, Xiaojia; Lee, Keun Seok; Ng, Ting Ying; Ridolfi, Antonia; Noel-Baron, Florence; Ringeisen, Francois; Jiang, Zefei

    2017-04-11

    The current exploratory analysis was performed to evaluate the efficacy and safety of everolimus for treatment of human epidermal growth factor receptor 2-positive (HER2+) advanced breast cancer in the Asian subset of patients in the BOLERO-1 trial. Postmenopausal women with HER2+ advanced breast cancer, who had not received systemic therapy for advanced disease, were randomized 2:1 to receive everolimus or placebo, plus trastuzumab and paclitaxel. The two primary end points were investigator-assessed progression-free survival (PFS) in the full population and in the hormone receptor-negative (HR-) subpopulation. Secondary end points included assessment of the objective response rate, the clinical benefit rate, and safety. In the Asian subset, median PFS was similar in the everolimus (n = 198) and placebo (n = 105) arms in the full analysis set (hazard ratio = 0.82 (95% CI 0.61-1.11)). In the HR- subpopulation, everolimus prolonged median PFS by 10.97 months vs placebo (25.46 vs 14.49 months; hazard ratio = 0.48 (95% CI 0.29-0.79)). In the everolimus arm of the Asian subset, the most common adverse events of any grade were stomatitis (62.2%), diarrhea (48.0%), rash (43.4%) and neutropenia (42.3%). Neutropenia (grade 3: 27.6%; grade 4: 4.6%) and decreased neutrophil count (grade 3: 11.2%; grade 4: 3.6%) were the most frequent grade 3/4 adverse events. Serious adverse events included pneumonia (5.1%), pneumonitis (3.1%), and interstitial lung disease (3.1%). There were three deaths (1.5%) during treatment in the everolimus arm vs none in the placebo arm. The efficacy and safety of everolimus plus trastuzumab and paclitaxel as first-line treatment for HER2+ advanced breast cancer in the Asian subset was consistent with that reported previously in the overall population. ClinicalTrials.gov, NCT00876395 . Registered on 2 April 2009.

  18. Early Introduction of Everolimus Immunosuppressive Regimen in Liver Transplantation with Extra-Anatomic Aortoiliac-Hepatic Arterial Graft Anastomosis

    Directory of Open Access Journals (Sweden)

    Emanuele Felli

    2014-01-01

    Full Text Available Liver transplantation is the treatment of choice for patients with acute and chronic end-stage liver disease, when no other medical treatment is possible. Despite high rates of 1- to 5-year survival, long-term adverse effects of immunosuppressant agents remain of major concern. Current research and clinical efforts are made to develop immunosuppressant agents that minimize adverse effects along with a low rate of graft rejection. Tailoring immunosuppressive therapy to individual patients by the use of proliferation signal inhibitors seems to be the best way to minimize toxicity and increase efficacy. Recently everolimus has been introduced in clinical practice; among its adverse effects an increased incidence of arterial graft thrombosis in renal transplants, vascular anastomosis leakage, impaired wound healing, and thrombotic microangiopathy have been reported. We present the case of a 54-year-old patient submitted to liver transplantation for end-stage liver disease treated by an extra-anatomic aortoiliac-hepatic arterial graft anastomosis and early postoperative introduction of everolimus for acute renal failure. Postoperative period was characterized by two abdominal collections and reactivation of cytomegalovirus infection that were treated by percutaneous drainage and antiviral therapy, respectively; the patient is well after 8-month followup with patency of the arterial conduit and no leakage.

  19. Cabozantinib Versus Everolimus in Patients with Advanced Renal Cell Carcinoma: Results of a Randomised Phase III Trial (METEOR

    Directory of Open Access Journals (Sweden)

    Toni Choueiri

    2015-11-01

    Full Text Available The METEOR trial of cabozantinib versus everolimus in advanced renal cell carcinoma (RCC was reported by Prof Choueiri at the European Cancer Congress 2015. This presentation follows the publication in the New England Journal of Medicine of the METEOR trial back-to-back with the CheckMate 025 trial of nivolumab versus everolimus in the same patient setting. Excitingly, these trials demonstrated, for the first time, significant benefits over the standard of care for heavily pre-treated patients with advanced RCC. Cabozantinib, an oral multi-targeted tyrosine kinase inhibitor (TKI aims to address the challenge of resistance to targeted therapy with TKIs. While the METEOR trial has not yet reached its final analysis of overall survival (OS, the clear progression-free survival (PFS benefit, acceptable safety profile, and similar tolerability to other TKIs shown by cabozantinib indicate that this represents a promising new treatment option for second-line or subsequent therapy for patients with advanced RCC.

  20. Comparison of Five-Year Outcome of Percutaneous Coronary Intervention With Coronary Artery Bypass Grafting in Triple-Vessel Coronary Artery Disease (from the Coronary Revascularization Demonstrating Outcome Study in Kyoto PCI/CABG Registry Cohort-2).

    Science.gov (United States)

    Shiomi, Hiroki; Morimoto, Takeshi; Furukawa, Yutaka; Nakagawa, Yoshihisa; Tazaki, Junichi; Sakata, Ryuzo; Okabayashi, Hitoshi; Hanyu, Michiya; Shimamoto, Mitsuomi; Nishiwaki, Noboru; Komiya, Tatsuhiko; Kimura, Takeshi

    2015-07-01

    Studies evaluating long-term (≥5 years) outcomes of percutaneous coronary intervention (PCI) using drug-eluting stents compared with coronary artery bypass grafting (CABG) in patients with triple-vessel coronary artery disease (TVD) are still limited. We identified 2,978 patients with TVD (PCI: n = 1,824, CABG: n = 1,154) of 15,939 patients with first coronary revascularization enrolled in the Coronary Revascularization Demonstrating Outcome Study in Kyoto PCI/CABG Registry Cohort-2. The primary outcome measure in the present analysis was a composite of death, myocardial infarction (MI), and stroke. Median follow-up duration for the surviving patients was 1,973 days (interquartile range 1,700 to 2,244). The cumulative 5-year incidence of death/MI/stroke was significantly higher in the PCI group than in the CABG group (28.2% vs 24.0%, log-rank p = 0.006). After adjusting for confounders, the excess risk of PCI relative to CABG for death/MI/stroke remained significant (hazard ratio [HR] 1.38, 95% confidence interval [CI] 1.13 to 1.68, p = 0.002). The excess risks of PCI relative to CABG for all-cause death, MI, and any coronary revascularization were also significant (HR 1.38, 95% CI 1.10 to 1.74, p = 0.006; HR 2.81, 95% CI 1.69 to 4.66, p PCI and CABG groups (HR 0.88, 95% CI 0.61 to 1.26, p = 0.48). There were no interactions for the primary outcome measure between the mode of revascularization (PCI or CABG) and the subgroup factors such as age, diabetes, and Synergy Between PCI With Taxus and Cardiac Surgery score. In conclusion, CABG compared with PCI was associated with better long-term outcome in patients with TVD. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Large coronary intramural hematomas

    DEFF Research Database (Denmark)

    Antonsen, Lisbeth; Thayssen, Per; Jensen, Lisette Okkels

    2015-01-01

    Isolated spontaneous coronary intramural hematoma is a unique subset of spontaneous coronary artery dissection that is characterized by a hemorrhage limited to the medial-adventitial layers, causing subsequent hematoma formation without visible intimal flaps. It is an infrequent and serious...... diagnostics and treatment strategy. Coronary intramural hematomas can also occur iatrogenically, as a complication to percutaneous coronary intervention (PCI). Coronary angiography (CAG) has limited diagnostic value in the absence of intimal dissections, and lesions are often angiographically ambiguous....... Intravascular ultrasound (IVUS) is an important diagnostic tool in establishing the correct diagnosis, as it provides a complete vessel wall assessment, and enables morphometric information regarding the magnitude and severity of the underlying hematoma. Due to the rarity of this clinical scenario...

  2. Lifetime cost of everolimus vs axitinib in patients with advanced renal cell carcinoma who failed prior sunitinib therapy in the US.

    Science.gov (United States)

    Perrin, Allison; Sherman, Steven; Pal, Sumanta; Chua, Andrew; Gorritz, Magdaliz; Liu, Zhimei; Wang, Xufang; Culver, Kenneth; Casciano, Roman; Garrison, Louis P

    2015-03-01

    Everolimus and axitinib are approved in the US to treat patients with advanced renal cell carcinoma (RCC) after failure on sunitinib or sorafenib, and one prior systemic therapy (e.g., sunitinib), respectively. Two indirect comparisons performed to evaluate progression-free survival in patients treated with everolimus vs axitinib suggested similar efficacy between the two treatments. Therefore, this analysis compares the lifetime costs of these two therapies among sunitinib-refractory advanced RCC patients from a US payer perspective. A Markov model was developed to simulate a cohort of sunitinib-refractory advanced RCC patients and estimate the cost of treating patients with everolimus vs axitinib. The following health states were included: stable disease without adverse events (AEs), stable disease with AEs, disease progression (PD), and death. The model included the following resources: active treatments, post-progression treatments, adverse events, physician and nurse visits, scans and tests, and palliative care. Resource utilization inputs were derived from a US claims database analysis. Additionally, a 3% annual discount rate was applied to costs, and the robustness of the model results was tested by conducting sensitivity analyses, including those on dosing scheme and post-progression treatment costs. Base case results demonstrated that patients treated with everolimus cost an average of $12,985 (11%) less over their lifetimes than patients treated with axitinib. The primary difference in costs was related to active treatment, which was largely driven by axitinib's higher dose intensity. RESULTS remained consistent across sensitivity analyses for AE and PD treatment costs, as well as dose intensity and discount rates. The results suggest that everolimus likely leads to lower lifetime costs than axitinib for sunitinib-refractory advanced RCC patients in the US.

  3. Zotarolimus-eluting stent for the treatment of recurrent, severe carotid artery in-stent stenosis in the TARGET-CAS population.

    Science.gov (United States)

    Tekieli, Lukasz; Pieniazek, Piotr; Musialek, Piotr; Kablak-Ziembicka, Anna; Przewlocki, Tadeusz; Trystula, Mariusz; Moczulski, Zbigniew; Dzierwa, Karolina; Paluszek, Piotr; Podolec, Piotr

    2012-06-01

    To evaluate the safety and efficacy of a balloon-mounted drug-eluting stent (DES) for recurrent carotid in-stent stenosis (ISS). As part of our targeted carotid artery stenting (TARGET-CAS) protocol, neurological and ultrasound evaluations have been performed at 3, 6, and 12 months and then annually since 2001 in all carotid stent patients. For angiographically-confirmed >70% ISS, balloon angioplasty was performed as a first-line treatment. Recurrent ISS was treated with a 4.0-mm zotarolimus-eluting coronary stent (ZES) that was postdilated according to intravascular ultrasound imaging. Among the 1350 neuroprotected CAS procedures performed between January 2001 and March 2011, there were 7 (0.52%) patients (5 men; ages 51-72 years), all neurologically asymptomatic, with >70% recurrent ISS that occurred at 5 to 11 months after the initial balloon angioplasty treatment for ISS. ZES implantation under distal embolic protection was technically successful and uncomplicated. Angiographic stenosis was reduced from 84.6%±7.5% to 10.7%±3.6% (p<0.01). In 5 patients with ZES implanted fully within the self-expanding carotid stent, duplex ultrasound follow-up (mean 17 months, range 6-36) revealed no evidence of restenosis or stent fracture/deformation. In the 2 other patients, the ZES had been implanted for distal edge ISS such that the ZES protruded beyond the original carotid stent. This protruding segment of the ZES demonstrated deformation/kinking in both; in one, this led to symptomatic stent occlusion. The use of coronary ZES in the treatment of recurrent carotid ISS is feasible and appears effective provided the ZES is placed entirely within the original stent. Placement of a coronary ZES outside the carotid stent scaffold should be avoided.

  4. [Experience with the use of the bio-active stent coated with titanium nitric oxide compared with zotarolimus-eluting stent: experience of a unit medical high specialty].

    Science.gov (United States)

    Garcia-Gutierrez, Juan C; Palacios-Rodríguez, Juan M; Cordova-Correa, Horacio G; Becerra-Laguna, Carlos A; López-López, Hugo A; Salinas Aragón, Miguel A; García-Bonilla, Jorge

    2016-01-01

    The use of coronary stents in coronary angioplasty has evolved dramatically in its design, type materials, polymers, and a variety of drugs, the use of coronary stents covered nitric oxide have shown satisfactory results in practice, however compared to the results reported drug-eluting stents, there is little information. The aim of this study was to compare clinical outcomes of a stainless steel stent Bioactive nitric oxide coated titanium (BAS) and a drug-eluting stent zotarolimus (DES) in daily clinical practice. A retrospective, analytical, descriptive and comparative study aimed at evaluating the safety and efficacy of two devices with different characteristics in our population. The primary endpoints were: death, acute infarction (AMI), and re intervention injury Treated (RLT). A total of 759 patients were included in the study which was performed angioplasty to a single vessel. Were divided into two arms 382 with DES and 377 patients with BAS, the one year follow up was carried in 95%. After this follow-up period, primary points (cardiovascular death, myocardial infarction, TLR and stent thrombosis) for arm DES vs BAS; 9.5% vs 8.5% P=NS but with shorter periods of dual antiplatelet therapy for arm BAS 6.9±4.1 vs 11.1±2.5 months DES P=.0001. The results were independent of the clinical syndrome of presentation. After one year of follow no statistically significant difference in major clinical events, there was a trend in favour of BAS vs SM with respect to revascularization of the target lesion without reaching statistical significance. Copyright © 2015 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.

  5. Studies of post-elution concentration of 99m-Tc eluted from a gel type chromatographic generator

    International Nuclear Information System (INIS)

    Suzuki, Katia N.; Osso Junior, Joao Alberto

    2007-01-01

    The radiopharmaceuticals most used in Diagnostic Nuclear Medicine are those labeled with the metastable technetium ( 99m Tc) due to its ideal physical properties of decay (t 1/2 6.01 h, Eγ 140 keV), low cost and availability facilitated through the commercial generator 99 Mo / 99m Tc. This radionuclide is formed by the β - decay of 99 Mo adsorbed on an alumina column of the generator and collected in the form of sodium pertechnetate (Na 99m TcO 4 ) by elution with saline solution (0.9%). The Radiopharmacy Center (CR) of the IPEN-CNEN/SP developed a gel type chromatographic generator of MoZr with 99 Mo produced by 98 Mo(n, γ) 99 Mo reaction that occurs in IEA-R1 Nuclear Reactor. The gel is composed of zirconium molybdate with elution volume of 12 ml with an activity of 11100 MBq (300 mCi) producing a radioactive concentration of 925 MBq (34 mCi) / ml. The fission generator gives a higher radioactive concentration around 1850 MBq (69 mCi) / ml. The aim of this work is to study a system of post-elution concentration using ion exchange cartridges in tandem (cation - anion) for the attainment of a high enough radioactive concentration to meet the demand of market, with a proved quality. This system of concentration will be made based in the technique of solid phase extraction (SPE) using commercial cartridges of extraction, which contains the solid phase and eluent saline solution (0.9%). As the eluent results of this system used in the gel generator of MoZr will be compared with the fission generator currently produced by IPEN-CNEN/SP. (author)

  6. Studies of post-elution concentration of {sup 99m}-Tc eluted from a gel type chromatographic generator

    Energy Technology Data Exchange (ETDEWEB)

    Suzuki, Katia N.; Osso Junior, Joao Alberto [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)]. E-mail: norisuzuki6@yahoo.com.br; jaosso@ipen.br

    2007-07-01

    The radiopharmaceuticals most used in Diagnostic Nuclear Medicine are those labeled with the metastable technetium ({sup 99m}Tc) due to its ideal physical properties of decay (t{sub 1/2} 6.01 h, E{gamma} 140 keV), low cost and availability facilitated through the commercial generator {sup 99}Mo /{sup 99m}Tc. This radionuclide is formed by the {beta}{sup -} decay of {sup 99}Mo adsorbed on an alumina column of the generator and collected in the form of sodium pertechnetate (Na{sup 99m}TcO{sub 4}) by elution with saline solution (0.9%). The Radiopharmacy Center (CR) of the IPEN-CNEN/SP developed a gel type chromatographic generator of MoZr with {sup 99}Mo produced by {sup 98}Mo(n, {gamma}){sup 99}Mo reaction that occurs in IEA-R1 Nuclear Reactor. The gel is composed of zirconium molybdate with elution volume of 12 ml with an activity of 11100 MBq (300 mCi) producing a radioactive concentration of 925 MBq (34 mCi) / ml. The fission generator gives a higher radioactive concentration around 1850 MBq (69 mCi) / ml. The aim of this work is to study a system of post-elution concentration using ion exchange cartridges in tandem (cation - anion) for the attainment of a high enough radioactive concentration to meet the demand of market, with a proved quality. This system of concentration will be made based in the technique of solid phase extraction (SPE) using commercial cartridges of extraction, which contains the solid phase and eluent saline solution (0.9%). As the eluent results of this system used in the gel generator of MoZr will be compared with the fission generator currently produced by IPEN-CNEN/SP. (author)

  7. Transarterial chemoembolization with drug-eluting beads in hepatocellular carcinoma

    Science.gov (United States)

    Nam, Hee Chul; Jang, Bohyun; Song, Myeong Jun

    2016-01-01

    Transarterial chemoembolization (TACE) is a widely used standard treatment for patients with hepatocellular carcinoma (HCC) who are not suitable candidates for curative treatments. The rationale for TACE is that intra-arterial chemotherapy using lipiodol and chemotherapeutic agents, followed by selective vascular embolization, results in a strong cytotoxic effect as well as ischemia (conventional TACE). Recently, drug-eluting beads (DC Beads®) have been developed for transcatheter treatment of HCC to deliver higher doses of the chemotherapeutic agent and to prolong contact time with the tumor. DC Beads® can actively sequester doxorubicin hydrochloride from solution and release it in a controlled sustained fashion. Treatment with DC Beads® substantially reduced the amount of chemotherapeutic agent that reached the systemic circulation compared with conventional, lipiodol-based regimens, significantly reducing drug-related adverse events. In this article, we describe the treatment response, survival, and safety of TACE used with drug-eluting beads for the treatment of HCC and discuss future therapeutic possibilities. PMID:27833376

  8. Dynamics of silver elution from functionalised antimicrobial nanofiltration membranes.

    Science.gov (United States)

    Choudhari, S; Habimana, O; Hannon, J; Allen, A; Cummins, E; Casey, E

    2017-07-01

    In an effort to mitigate biofouling on thin film composite membranes such as nanofiltration and reverse osmosis, a myriad of different surface modification strategies has been published. The use of silver nanoparticles (Ag-NPs) has emerged as being particularly promising. Nevertheless, the stability of these surface modifications is still poorly understood, particularly under permeate flux conditions. Leaching or elution of Ag-NPs from the membrane surface can not only affect the antimicrobial characteristics of the membrane, but could also potentially present an environmental liability when applied in industrial-scale systems. This study sought to investigate the dynamics of silver elution and the bactericidal effect of an Ag-NP functionalised NF270 membrane. Inductively coupled plasma-atomic emission spectroscopy was used to show that the bulk of leached silver occurred at the start of experimental runs, and was found to be independent of salt or permeate conditions used. Cumulative amounts of leached silver did, however, stabilise following the initial release, and were shown to have maintained the biocidal characteristics of the modified membrane, as observed by a higher fraction of structurally damaged Pseudomonas fluorescens cells. These results highlight the need to comprehensively assess the time-dependent nature of bactericidal membranes.

  9. Recent developments in drug eluting devices with tailored interfacial properties.

    Science.gov (United States)

    Sanchez-Rexach, Eva; Meaurio, Emilio; Sarasua, Jose-Ramon

    2017-11-01

    Drug eluting devices have greatly evolved during past years to become fundamental products of great marketing importance in the biomedical field. There is currently a large diversity of highly specialized devices for specific applications, making the development of these devices an exciting field of research. The replacement of the former bare metal devices by devices loaded with drugs allowed the sustained and controlled release of drugs, to achieve the desired local therapeutic concentration of drug. The newer devices have been "engineered" with surfaces containing micro- and nanoscale features in a well-controlled manner, that have shown to significantly affect cellular and subcellular function of various biological systems. For example, the topography can be structured to form an antifouling surface mimicking the defense mechanisms found in nature, like the skin of the shark. In the case of bone implants, well-controlled nanostructured interfaces can promote osteoblast differentiation and matrix production, and enhance short-term and long-term osteointegration. In any case, the goal of current research is to design implants that induce controlled, guided, and rapid healing. This article reviews recent trends in the development of drug eluting devices, as well as recent developments on the micro/nanotechnology scales, and their future challenges. For this purpose medical devices have been divided according to the different systems of the body they are focused to: orthopedic devices, breathing stents, gastrointestinal and urinary systems, devices for cardiovascular diseases, neuronal implants, and wound dressings. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Elution of monomer from different bulk fill dental composite resins.

    Science.gov (United States)

    Cebe, Mehmet Ata; Cebe, Fatma; Cengiz, Mehmet Fatih; Cetin, Ali Rıza; Arpag, Osman Fatih; Ozturk, Bora

    2015-07-01

    The purpose of this study was to evaluate the elution of Bis-GMA, TEGDMA, HEMA, and Bis-EMA monomers from six bulk fill composite resins over four different time periods, using HPLC. Six different composite resin materials were used in the present study: Tetric Evo Ceram Bulk Fill (Ivoclar Vivadent, Amherst, NY), X-tra Fill (VOCO, Cuxhaven, Germany), Sonic Fill (Kerr, Orange, CA, USA), Filtek Bulk Fill (3M ESPE Dental Product, St. Paul, MN), SDR (Dentsply, Konstanz, Germany), EQUIA (GC America INC, Alsip, IL). The samples (4mm thickness, 5mm diameter) were prepared and polymerized for 20s with a light emitted diode unit. After fabrication, each sample was immediately immersed in 75wt% ethanol/water solution used as extraction fluid and stored in the amber colored bottles at room temperature. Ethanol/water samples were taken (0.5mL) at predefined time intervals:10m (T1), 1h (T2), 24h (T3) and 30 days (T4). These samples were analyzed by HPLC. The obtained data were analyzed with one-way ANOVA and Tukey HSD at significance level of pcomposites (pcomposite resins in all time periods and the amount of eluted monomers was increased with time. Copyright © 2015 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

  11. [Endarterectomy of the coronary arteries].

    Science.gov (United States)

    Fischer, V; Simkovic, I; Holoman, M; Verchvodko, P; Janotík, P; Galbánek, J; Hulman, M; Kostelnicák, J; Jurco, R; Slezák, J

    1992-02-01

    The authors analyze 50 patients with endarterectomy of the coronary arteries during the periods of 1972-1974 and 1988-1990. The results of endarterectomy of the right and left coronary artery provide evidence of its justification in indicated cases whereby contrary to some departments the results of endarterectomy of the left coronary artery are comparable with endarterectomy of the right coronary artery.

  12. [Absorbable coronary stents. New promising technology].

    Science.gov (United States)

    Erbel, Raimund; Böse, Dirk; Haude, Michael; Kordish, Igor; Churzidze, Sofia; Malyar, Nasser; Konorza, Thomas; Sack, Stefan

    2007-06-01

    revascularization rate of 23.8% which was below the 30% cut point of the study protocol. No myocardial Q wave infarction or death were reported. The primary endpoint was reached. During the follow-up period, vasomotion was tested in some of the patients. The proof of principle was confirmed: restoration of vasomotion during acetylcholine testing. The development of the absorbable magnesium stent, which was pushed forward by B. Heublein, Hanover, Germany, has been successful and opens new possibilities for treatment of coronary arteries. Permanent foreign-body implantation is avoided allowing further revascularization procedures in the future, bypass grafting, and restoration of vasomotion. Even prophylactic stenting in nonsignificant stenosis, like vulnerable lesions, may become a regular procedure. Noninvasive coronary imaging by CT and MRI is now possible. Stenting of children and in peripheral arteries may become a standard procedure. Currently, the degradation process of the magnesium stent has to be prolonged, and the neointima proliferation rate has to be reduced so that the DREAM (Drug-Eluting Absorbable Magnesium Stent) concept of Ron Waksman, Washington, DC, USA, can be realized.

  13. Size distribution of DNA molecules recovered from non-denaturing filter elution

    International Nuclear Information System (INIS)

    Bloecher, D.; Iliakis, G.

    1991-01-01

    DNA fragments removed from the filter during non-denaturing filter elution were collected and loaded on top of neutral sucrose gradients. Their size distribution was determined by low-speed centrifugation in neutral sucrose gradients. The average size of eluted DNA was found to be approximately 110 S; the average size of DNA collected after short elution times was found to be slightly larger than after long elution times. It is concluded that the size of eluted DNA fragments is not correlated with elution rate, and it is proposed that shear forces generated at the filter pores cause degradation of the DNA. Comparison of sedimentation profiles of carefully prepared cellular DNA before and after elution revealed that generated shear forces during elution break down DNA to an extent equivalent to around 20 000 DNA double-strand breaks (dsb) per G 1 cell. The size of DNA fragments decreased with increasing radiation dose; five times more dsb were found than expected after exposure to radiation alone. It is proposed that excess of dsb may derive from the transformation of other radiation-induced lesions to dsb under the action of shear forces generated during elution. (author)

  14. Selective coronary scintigraphy

    International Nuclear Information System (INIS)

    Gambini, D.-J.

    1975-01-01

    Isotopic techniques occupy a leading place amongst examinations practicable on coronary patients because of their reliability and the safety and simplicity of their use. The present work reviews the possible applications of selective coronary scintigraphy in pathology. After a brief discussion on scintigraphy, isotopic techniques for myocardium research, coronarography and other methods to study local myocardium perfusion the theoretical bases for the use of the exploration are studied, the techniques and methods employed are reported and the results discussed. Coronary scintigraphy consists of selective injection in the two coronary arteries previously catheterized during a coronarography, of two different populations of microspheres labelled with two physically short-lived indicators: 15μ 99m Tc-labelled serumalbumin microspheres, 10 to 15μ In-labelled siderophiline microspheres. Various studies have shown the complete harmlessness of the exploration when certain precautions are taken regarding the size and number of the spheres. The microspheres disperse into the downstream arterial territory proportionally to the number of capillaries present in the different parts of the irrigated region, and are temporarily stopped in the precapillaries. The preparation of the different images needed to interpret the Face and OAG examination for the left coronary, then for the right coronary, is carried out at the end of the coronarography and lasts about 45 minutes. It is also possible by selective injection in the aorta-coronary bridges to judge their functional condition by observation of the regions they irrigate. 56 patients of the Necker hospital cardiological clinic have been examined [fr

  15. Congenital coronary artery fistula

    International Nuclear Information System (INIS)

    Oh, Yeon Hee; Kim, Hong; Zeon, Seoc Kil; Suh, Soo Jhi

    1986-01-01

    Congenital coronary artery fistula (CCAF) is communication of a coronary artery or its main branch with one of the atria or ventricles, the coronary sinus, the superior vena cava, or the pulmonary artery. In Korean peoples, only 4 cases of the CCAF were reported as rare as worldwide and authors want to report another case of CCAF, confirmed by operation. 10-year-old girl shows a fistula between sinus node artery of the right coronary artery and right atrium on root aortogram with left-to-right shunt and Qp/Qs=1.58, in which simple ligation of the sinus node artery from right coronary artery was performed. All of the 5 Korean CCAF (4 were previously reported and 1 of authors) were originated from right coronary artery, and of which 4 were opening into right ventricle and 1 of authors were into right atrium. Associated cardiac anomaly was noted in only 1 case as single coronary artery. Ages were from 9 months of age to 10 years old and no adult left case were found. 3 were female and 2 were male patients.

  16. Coronary CT angiography

    Energy Technology Data Exchange (ETDEWEB)

    Dewey, Marc [Charite - Universitaetsmedizin Berlin (Germany). Inst. fuer Radiologie

    2009-07-01

    Coronary CT angiography has attained increasing scientific attention at academic institutions and has become a highly accurate diagnostic modality. Extending this knowledge into a practice setting is the purpose of 'Coronary CT Angiography'. This book will assist you in integrating cardiac CT into your daily practice, while also giving an overview of the current technical status and applications. The specific features of scanners from all four main vendors are also presented providing an objective overview of noninvasive coronary angiography using CT. (orig.)

  17. OrbusNeich fully absorbable coronary stent platform incorporating dual partitioned coatings.

    Science.gov (United States)

    Cottone, Robert J; Thatcher, G Lawrence; Parker, Sherry P; Hanks, Laurence; Kujawa, David A; Rowland, Stephen M; Costa, Marco; Schwartz, Robert S; Onuma, Yoshinobu

    2009-12-15

    The field of stent based tissue engineering continues to revolutionise modern medicine by designing novel materials to restore vascular tissue function. Accordingly, the following discussion examines a novel, absorbable, polymeric scaffold engineered in combination with dual therapeutic coating, enabling locally administered temporary scaffolding in the coronary arteries for long term vascular patency and repair. This coronary stent platform consists of an absorbable polymeric material stent structure that incorporates a dual partitioned coating, by means of pro-healing EPC (endothelial progenitor cell) capture technology allowing for rapid endothelial coverage, and an absorbable polymer matrix with sustained elution of sirolimus, a drug controlling neointimal proliferation. This paper provides a brief overview of the various innovations developed by OrbusNeich to create this fully absorbable coronary device platform.

  18. Comparison of the sirolimus-eluting versus paclitaxel-eluting coronary stent in patients with diabetes mellitus: the diabetes and drug-eluting stent (DiabeDES) randomized angiography trial

    DEFF Research Database (Denmark)

    Maeng, Michael; Jensen, Lisette Okkels; Galloe, Anders Michael

    2008-01-01

    group (0.23 +/- 0.54 vs 0.44 +/- 0.52 mm, p = 0.025). Angiographic in-segment restenosis at 8-month follow-up, a secondary end point, was present in 16 patients (Cypher, n = 6; Taxus, n = 10; p = 0.24). Target lesion revascularization was performed in 5 patients (6.5%) and 9 patients (11.......8%) in the Cypher and Taxus groups, respectively (p = 0.25). Definite stent thrombosis was observed in 2 patients (in the Taxus group), no patients had probable stent thrombosis, and 1 patient in each group had possible stent thrombosis. Major adverse cardiac events (cardiac death, myocardial infarction, definite...

  19. Determinants of protein elution rates from preparative ion-exchange adsorbents.

    Science.gov (United States)

    Angelo, James M; Lenhoff, Abraham M

    2016-04-01

    The rate processes involved in elution in preparative chromatography can affect both peak resolution and hence selectivity as well as practical factors such as facility fit. These processes depend on the physical structure of the adsorbent particles, the amount of bound solute, the solution conditions for operation or some combination of these factors. Ion-exchange adsorbents modified with covalently attached or grafted polymer layers have become widely used in preparative chromatography. Their often easily accessible microstructures offer substantial binding capacities for biomolecules, but elution has sometimes been observed to be undesirably slow. In order to determine which physicochemical phenomena control elution behavior, commercially available cellulosic, dextran-grafted and unmodified agarose materials were characterized here by their elution profiles at various conditions, including different degrees of loading. Elution data were analyzed under the assumption of purely diffusion-limited control, including the role of pore structure properties such as porosity and tortuosity. In general, effective elution rates decreased with the reduction of accessible pore volume, but differences among different proteins indicated the roles of additional factors. Additional measurements and analysis, including the use of confocal laser scanning microscopy to observe elution within single chromatographic particles, indicated the importance of protein association within the particle during elution. The use of protein stabilizing agents was explored in systems presenting atypical elution behavior, and l-arginine and disaccharide excipients were shown to alleviate the effects for one protein, lysozyme, in the presence of sodium chloride. Incorporation of these excipients into eluent buffer gave rise to faster elution and significantly lower pool volumes in elution from polymer-modified adsorbents. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Development of DNA elution method to detect irradiated foodstuff

    International Nuclear Information System (INIS)

    Copin, M.P.; Bourgeois, C.M.

    1991-01-01

    The aim of the work is to develop a reliable method to detect whether a fresh and frozen foodstuff has been irradiated. The molecule of DNA is one of the targets of ionizing radiation. The induction of three major classes of lesion have been shown. Double strand breaks, single strand breaks and base damage. Among the different techniques used to observe and quantify the strand breaks, techniques of elution are very interesting. The method proposed consisted of a filtration of the DNA at the atmospheric pressure and in non denaturing conditions. The amount of DNA retained on the filter is measured after being suitably labelled by microfluorometry. A difference in the amount of DNA retained on a filter of 2 μm from a lysed muscular tissue sample between a frozen Norway lobster which has been irradiated and one which has not, is observed. 7 refs

  1. Alkaline elution of uranium and molybdenum and their recovery

    International Nuclear Information System (INIS)

    Song Wenlan; Wu Peisheng; Zhao Pinzhi; Tao Dening; Xie Chaoyan

    1987-01-01

    The uranium and molybdenum can be simultaneously eluted by using eluant (NH 4 ) 2 CO 3 + (NH 4 ) 2 SO 4 from resin loaded uranium and molybdenum. The ADU is precipitated from eluant by volatilization of ammonia. The molybdenum is extracted by TFA-TBP-kerosene from the filtrate at pH 3.0-3.2 with molybdenum extraction > 98%. Uranium is nearly not extracted. The precipitation of Mo is reached by sulphuric acid after stripping and the ammonium multimolybdate is obtained. This process can give the total recovery more than 99% for U and 90% for Mo. Because of the use of sulphate salt system, the hazard of NO 3 - can be avoided

  2. Quantitation of radiolabeled compounds eluting from the HPLC system

    International Nuclear Information System (INIS)

    Kessler, M.J.

    1982-01-01

    Three techniques are compared for the quantitation of various radiolabeled compounds eluting in the high performance liquid chromatography system. The first technique requires fraction-collecting the effluent from the HPLC, removing an aliquot to scintillation vials, and counting each fraction in a liquid scintillation counter. The second uses direct interface of the HPLC effluent to a flow-through radioactivity detector. The third involves quantitation of various radiolabeled compounds (proteins, steroids, and nucleotides) by splitting the effluent from the HPLC with an electronic steam splitter, thus diverting a present portion to the fraction collector for further chemical characterization and the remainder to the radioactivity flow detector for direct quantitation. A direct comparison of the chromatograms and the radioactivity counting efficiencies of these three techniques is presented

  3. Acute Coronary Syndrome

    Science.gov (United States)

    ... heart cells are dying. An electrocardiogram (ECG or EKG) can diagnose an acute coronary syndrome by measuring ... Privacy Policy Popular Articles 1 Understanding Blood Pressure Readings 2 Sodium and Salt 3 Heart Attack Symptoms ...

  4. Coronary artery fistula

    Science.gov (United States)

    ... PA: Elsevier Saunders; 2015:chap 84. Friedman AH, Silverman NH. Congenital anomalies of the coronary arteries. In: ... provided by VeriMed Healthcare Network. Also reviewed by David Zieve, MD, MHA, Isla Ogilvie, PhD, and the ...

  5. Coronary Artery Disease

    DEFF Research Database (Denmark)

    Christiansen, Morten Krogh

    2017-01-01

    A family history of coronary artery disease (CAD) is an important risk factor for adverse coronary events, in particular if the disease has an early onset. The risk of CAD is influenced by genetic and environmental factors with a greater genetic contribution earlier in life. Through recent years......), and to characterize and quantify subclinical atherosclerosis in their relatives. Furthermore, the aim was to explore the impact of common genetic risk variants on the age of onset, familial clustering and disease severity. In study I, 143 patients with early- onset CAD were recruited from the Western Denmark Heart...... Registry and risk factor control was evaluated. The study revealed that risk factors are common in early-onset CAD and that a large room for risk factor improvement remains. In study II, we used coronary computed tomography angiography to compare the coronary plaque burden and characteristics between 88...

  6. Auxetic coronary stent endoprosthesis

    DEFF Research Database (Denmark)

    Amin, Faisal; Ali, Murtaza Najabat; Ansari, Umar

    2014-01-01

    BACKGROUND: Cardiovascular heart disease is one of the leading health issues in the present era and requires considerable health care resources to prevent it. The present study was focused on the development of a new coronary stent based on novel auxetic geometry which enables the stent to exhibit...... a negative Poisson's ratio. Commercially available coronary stents have isotropic properties, whereas the vascular system of the body shows anisotropic characteristics. This results in a mismatch between anisotropic-isotropic properties of the stent and arterial wall, and this in turn is not favorable...... for mechanical adhesion of the commercially available coronary stents with the arterial wall. It is believed that an auxetic coronary stent with inherent anisotropic mechanical properties and negative Poisson's ratio will have good mechanical adhesion with the arterial wall. METHODS: The auxetic design...

  7. Acute coronary syndrome

    Science.gov (United States)

    ... Have plenty of fruits, veggies, whole grains, and lean meats. Try to limit foods high in cholesterol ... et al. 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary ...

  8. Thrombosis of second-generation drug-eluting stents in real practice results from the multicenter Spanish registry ESTROFA-2 (Estudio Español Sobre Trombosis de Stents Farmacoactivos de Segunda Generacion-2).

    Science.gov (United States)

    de la Torre Hernández, José M; Alfonso, Fernando; Gimeno, Federico; Diarte, Jose A; Lopez-Palop, Ramón; Pérez de Prado, Armando; Rivero, Fernando; Sanchis, Juan; Larman, Mariano; Diaz, Jose F; Elizaga, Jaime; Moreiras, Javier Martín; Gomez Jaume, Alfredo; Hernández, José M; Mauri, Josepa; Recalde, Angel Sánchez; Bullones, Juan A; Rumoroso, Jose R; Del Blanco, Bruno García; Baz, Jose A; Bosa, Francisco; Botas, Javier; Hernández, Felipe

    2010-09-01

    This study sought to evaluate second-generation drug-eluting stent (DES) thrombosis in clinical practice. First-generation DES are associated with a significant incidence of late thrombosis. There is paucity of data regarding real practice late thrombosis incidence and predictors with second-generation DES, zotarolimus-eluting stent (ZES), and everolimus-eluting stents (EES). A prospective, large-scale, non-industry-linked multicenter registry was designed. Complete clinical-procedural data and systematic follow-up of all patients treated with these stents was reported in a dedicated registry supported by the Spanish Working Group on Interventional Cardiology. From 2005 to 2008, 4,768 patients were included in 34 centers: 2,549 treated with ZES, and 2,219 with EES. The cumulative incidence of definite/probable thrombosis for ZES was 1.3% at 1 year and 1.7% at 2 years and for EES 1.4% at 1 year and 1.7% at 2 years (p = 0.8). The increment of definite thrombosis between the first and second year was 0.2% and 0.25%, respectively. In a propensity score analysis, the incidence remained very similar. Ejection fraction (adjusted hazard ratio [HR]: 0.97; 95% confidence interval [CI]: 0.95 to -0.99; p = 0.008), stent diameter (adjusted HR: 0.37; 95% CI: 0.17to 0.81; p = 0.01) and bifurcations (adjusted HR: 2.1; 95% CI: 1.14 to 3.7; p = 0.02) emerged as independent predictors of thrombosis. In the subgroup of patients with bifurcations, the use of ZES was independently associated with a higher thrombosis rate (adjusted HR: 4; 95% CI: 1.1 to 13; p = 0.03). In a real practice setting, the incidence of thrombosis at 2 years with ZES and EES was low and quite similar. The incidence of very late thrombosis resulted lower than was reported in registries of first-generation DES. In the subset of bifurcations, the use of ZES significantly increased the risk of thrombosis. Copyright © 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  9. Coronary hemodynamics in vasospastic angina

    International Nuclear Information System (INIS)

    Matsumura, Kentaro; Kubota, Shinobu; Serizawa, Takashi; Nakase, Emiko; Kawai, Ichiro; Saito, Takayuki

    1991-01-01

    To evaluate the coronary circulation and myocardial perfusion dynamics, we performed left coronary digital subtraction angiography (DSA) in 35 patients with vasospastic angina. The left coronary circulation time (CCT) measured from the proximal left coronary artery to the coronary sinus was 5.77±0.86 sec, and the left epicardial conducting artery transmission time (CAT) measured from the proximal left coronary artery to the apical area was 2.65±0.82 sec in normal controls. The CCT and CAT were significantly prolonged in patients with vasospastic angina, indicating that the coronary peripheral vascular resistance is probably greater after the cessation of nitrates and Ca ++ -antagonists. After the intracoronary injection of ergonovine malate, the CCT was slightly shortened, but the apical T 1/2 was significantly prolonged in patients with vasospastic angina. This suggested that coronary vasospasm is present not only in the epicardial arteries but also in coronary arteries with peripheral resistance. These phenomena were not observed in normal controls. We performed left coronary DSA after conventional left coronary cineangiography. When the CCT exceeded 6.7 sec, we considered that the coronary circulation was significantly impaired. We concluded that the coronary DSA is very useful for evaluating abnormal coronary circulation in patients with vasospastic angina during myocardial perfusion. (author)

  10. Coronary tortuosity: a long and winding road.

    NARCIS (Netherlands)

    Zegers, E.S.; Meursing, B.T.J.; Oude Ophuis, A.J.M.

    2007-01-01

    Coronary tortuosity is a phenomenon often encountered by cardiologists performing coronary angiography. The aetiology and clinical importance of coronary tortuosity are still unclear. Coronary tortuosity without fixed atherosclerotic stenosis in patients with angina pectoris and an abnormal exercise

  11. Coronary Artery Anomalies in Animals

    Directory of Open Access Journals (Sweden)

    Brian A. Scansen

    2017-04-01

    Full Text Available Coronary artery anomalies represent a disease spectrum from incidental to life-threatening. Anomalies of coronary artery origin and course are well-recognized in human medicine, but have received limited attention in veterinary medicine. Coronary artery anomalies are best described in the dog, hamster, and cow though reports also exist in the horse and pig. The most well-known anomaly in veterinary medicine is anomalous coronary artery origin with a prepulmonary course in dogs, which limits treatment of pulmonary valve stenosis. A categorization scheme for coronary artery anomalies in animals is suggested, dividing these anomalies into those of major or minor clinical significance. A review of coronary artery development, anatomy, and reported anomalies in domesticated species is provided and four novel canine examples of anomalous coronary artery origin are described: an English bulldog with single left coronary ostium and a retroaortic right coronary artery; an English bulldog with single right coronary ostium and transseptal left coronary artery; an English bulldog with single right coronary ostium and absent left coronary artery with a prepulmonary paraconal interventricular branch and an interarterial circumflex branch; and a mixed-breed dog with tetralogy of Fallot and anomalous origin of all coronary branches from the brachiocephalic trunk. Coronary arterial fistulae are also described including a coronary cameral fistula in a llama cria and an English bulldog with coronary artery aneurysm and anomalous shunting vessels from the right coronary artery to the pulmonary trunk. These examples are provided with the intent to raise awareness and improve understanding of such defects.

  12. Drug-eluting stents studies in mice: Do we need atherosclerosis to study restenosis?

    NARCIS (Netherlands)

    Pires, N.M.M.; Jukema, J.W.; Daemen, M.J.A.P.; Quax, P.H.A.

    2006-01-01

    In 2001, the first human study with drug-eluting stents (DES) was published showing a nearly complete abolition of restenosis by using a sirolimus-eluting stent. This success was very encouraging to test new compounds in combination with the DES platform. Nevertheless, several other anti-restenotic

  13. Possibility of obtaining enriched americium-242g by the elution of recoil atoms from zeolite

    Energy Technology Data Exchange (ETDEWEB)

    Shafiev, A I; Vityutnev, V M; Ivanov, V M; Yakovlev, G N

    1974-12-31

    On the example of production the possibility of obtaining enriched actinide isotopes by the elution of recotl atoms with the use of a zeolite- americium-241 target was shown. The enrichment factor and the recoil atoms of / sup 242g/Am yield depend on preliminary target treatment and solution composition used for elution. (auth)

  14. Elution behavior of heavy metals from cement solidified products of incinerated ash waste - 59102

    International Nuclear Information System (INIS)

    Meguro, Yoshihiro; Kawato, Yoshimi; Nakayama, Takuya; Tomioka, Osamu; Mitsuda, Motoyuki

    2012-01-01

    A method, in which incinerated ash is solidified with a cement material, has been developed to dispose radioactive incinerated ash waste. In order to bury the solidified product, it is required that elution of hazardous heavy metals included in the ash from the solidified products is inhibited. In this study, the elution behavior of the heavy metals from the synthetic solidified products, which included Pb(II), Cd(II), and Cr(VI) and were prepared using ordinary portland cement (OPC), blast furnace slag cement (BFS), or a cement material that showed low alkalinity (LA-Cement), was investigated. Several chemicals and materials were added as additive agents to prevent the elution of the heavy metals. When OPC was used, Cd elution was inhibited, but Pb and Cr were not enough even using the additive agent examined. FeSO 4 and Na 2 S additive agents worked effective to inhibit elution of Cr. When BFS was used, the elution of Pb, Cd and Cr was inhibited for the all products prepared. In the case of LA-Cement, the elution of Pb and Cd was inhibited for the all products, but only the product that was added FeSO 4 showed good result of the elution of Cr. (authors)

  15. Cefoperazone and cefoperazone-sulbactam susceptibility tests with anaerobic bacteria by the thioglycolate disk elution method.

    OpenAIRE

    Barry, A L; Packer, R R; Jones, R N

    1985-01-01

    Tests were performed with 104 anaerobic microorganisms to evaluate the thioglycolate disk elution technique for the detection of resistance to cefoperazone and cefoperazone-sulbactam. An unacceptably high false-resistance rate and a poor reproducibility record make the disk elution procedure unsatisfactory for routine testing of this drug or combination of drugs.

  16. Alternative sample-introduction technique to avoid breakthrough in gradient-elution liquid chromatography of polymers

    NARCIS (Netherlands)

    Reingruber, E.; Bedani, F.; Buchberger, W.; Schoenmakers, P.

    2010-01-01

    Gradient-elution liquid chromatography (GELC) is a powerful tool for the characterization of synthetic polymers. However, gradient-elution chromatograms often suffer from breakthrough phenomena. Breakthrough can be averted by using a sample solvent as weak as the mobile phase. However, this approach

  17. Real-world effectiveness of everolimus-based therapy versus fulvestrant monotherapy in HR(+)/HER2(-) metastatic breast cancer.

    Science.gov (United States)

    Hao, Yanni; Lin, Peggy L; Xie, Jipan; Li, Nanxin; Koo, Valerie; Ohashi, Erika; Wu, Eric Q; Rogerio, Jaqueline

    2015-08-01

    Assessing real-world effectiveness of everolimus-based therapy (EVE) versus fulvestrant monotherapy (FUL) among postmenopausal women with hormone receptor-positive (HR(+))/HER2(-) metastatic breast cancer (mBC) after progression on nonsteroidal aromatase inhibitor (NSAI). Medical charts of community-based patients who received EVE or FUL for mBC after NSAI were examined. Progression-free survival (PFS), time on treatment and time to chemotherapy were compared using Kaplan-Meier curves and Cox proportional hazards models adjusting for line of therapy and patient characteristics. 192 patients received EVE and 156 FUL. After adjusting for patient characteristics, EVE was associated with significantly longer PFS than FUL (hazard ratio: 0.71; p = 0.045). EVE was associated with better PFS than FUL among NSAI-refractory postmenopausal HR(+)/HER2(-) mBC patients.

  18. Vitamins C and K3: A Powerful Redox System for Sensitizing Leukemia Lymphocytes to Everolimus and Barasertib.

    Science.gov (United States)

    Ivanova, Donika; Zhelev, Zhivko; Lazarova, Dessislava; Getsov, Plamen; Bakalova, Rumiana; Aoki, Ichio

    2018-03-01

    Recent studies provided convincing evidence for the anticancer activity of combined application of vitamin C and pro-vitamin K3 (menadione). The molecular pathways underlying this process are still not well established. The present study aimed to investigate the effect of the combination of vitamin C plus pro-vitamin K3 on the redox status of leukemia and normal lymphocytes, as well as their sensitizing effect for a variety of anticancer drugs. Cytotoxicity of the substances was analyzed by trypan blue staining and automated counting of live and dead cells. Apoptosis was analyzed by fluorescein isothiocyanate-annexin V test. Oxidative stress was evaluated by the intracellular levels of reactive oxygen and nitrogen species and protein-carbonyl products. Combined administration of 300 μM vitamin C plus 3 μM pro-vitamin K3 reduced the viability of leukemia lymphocytes by ~20%, but did not influence the viability of normal lymphocytes. All combinations of anticancer drug plus vitamins C and K3 were characterized by synergistic cytotoxicity towards Jurkat cells, compared to cells treated with drug alone for 24 h. In the case of barasertib and everolimus, this synergistic cytotoxicity increased within 72 hours. It was accompanied by strong induction of apoptosis, but a reduction of level of hydroperoxides and moderately increased protein-carbonyl products in leukemia cells. Leukemia lymphocytes were more sensitive to combined administration of anticancer drug (everolimus or barasertib) plus vitamins C and K3, compared to normal lymphocytes. The combination of vitamin C plus K3 seems to be a powerful redox system that could specifically influence redox homeostasis of leukemia cells and sensitize them to conventional chemotherapy. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  19. Selective elution of HLA antigens and beta 2-microglobulin from human platelets by chloroquine diphosphate

    International Nuclear Information System (INIS)

    Kao, K.J.

    1988-01-01

    To determine whether chloroquine can specifically elute HLA antigens and beta 2-microglobulin (beta 2-M) from the platelet surface, quantitative immunofluorescence flow cytometry and monoclonal antibodies were used to show that HLA antigens and beta 2-M were proportionally eluted from the platelet surface without affecting the membrane glycoproteins IIb and IIIa. Second, an autoradiogram of electrophoresed I-125-labeled platelets showed that only beta 2-M but not other I-125-labeled membrane proteins could be eluted. Although HLA antigens were poorly labeled by I-125 and could not be detected on the autoradiogram, the eluted HLA antigens could be detected by anti-HLA monoclonal antibody and immunoblotting techniques. No loss of plasma membrane integrity was observed by transmission electron microscopy after chloroquine treatment of platelets. The results indicate that chloroquine selectively elutes HLA antigens and their noncovalently associated beta 2-M without affecting other integral platelet membrane proteins

  20. ASSOCIATION OF HIGH LIPOPROTEIN(a LEVELS WITH CORONARY ARTERY PATENCY DURING THE FIRST YEAR AFTER PERCUTANEOUS CORONARY INTERVENTIONS

    Directory of Open Access Journals (Sweden)

    M. V. Ezhov

    2011-01-01

    Full Text Available Objective: to study an association of high lipoprotein(a [Lp(a] levels with the development of restenosis and the progression of coronaryatherosclerosis after percutaneous coronary interventions (PCI in patients with chronic coronary heart disease (CHD.Subjects and methods. From 502 enrolled patients (mean age 54.7 ± 8.9 years, 92 underwent routine percutaneous transluminal coronary angioplasty (PTCA, 270 had PTCA with the bare metal stent (BMS being implantation, 140 had PTCA using drug-eluting stents (DES. Functionalclasses III and IV angina have been registered in 337 (67 % patients; history of one myocardial infarction (MI was noted in 234 (47 % cases, 171 (34 % had experienced 2 or more MIs. Blood samples for lipid and Lp(a measurements were taken in all the patients. Restenosis was defined as at least 50 % lumen narrowing of the coronary artery segment after angioplasty. Coronary atherosclerosis progression was established in cases of the new occlusion occurring, as well as identifying a 10 % decrease in lumen diameter in comparison with baseline angiograms.Results. Repeated coronary angiography revealed the signs of restenosis in 103 of 243 patients. Dividing patients into 3 groups according to the type of intervention demonstrated that the level of Lp(a (median 25–75 % quartiles was significantly higher in the restenosis group after implantation of BMS (33; 11–62 and 16; 6–39 mg/dl, respectively; p = 0.014 versus those who had undergone DES implantation (23; 10–30 and 20; 6–60 mg/dl; p = 0.7 or balloon angioplasty (17; 4–48 and 9; 4–36 mg/dl; p = 0.3. Patients with progression of coronary atherosclerosis had difference only in Lp(a levels compared to the group without progression (36; 13–62 versus 12; 4–26 mg/dl, p < 0,001.Conclusion. During the first year after elective PCI Lp(a concentration determined the severity of coronary atherosclerosis in non-culprit lesionsand associated with the risk of in

  1. ASSOCIATION OF HIGH LIPOPROTEIN(a LEVELS WITH CORONARY ARTERY PATENCY DURING THE FIRST YEAR AFTER PERCUTANEOUS CORONARY INTERVENTIONS

    Directory of Open Access Journals (Sweden)

    M. V. Ezhov

    2014-07-01

    Full Text Available Objective: to study an association of high lipoprotein(a [Lp(a] levels with the development of restenosis and the progression of coronaryatherosclerosis after percutaneous coronary interventions (PCI in patients with chronic coronary heart disease (CHD.Subjects and methods. From 502 enrolled patients (mean age 54.7 ± 8.9 years, 92 underwent routine percutaneous transluminal coronary angioplasty (PTCA, 270 had PTCA with the bare metal stent (BMS being implantation, 140 had PTCA using drug-eluting stents (DES. Functionalclasses III and IV angina have been registered in 337 (67 % patients; history of one myocardial infarction (MI was noted in 234 (47 % cases, 171 (34 % had experienced 2 or more MIs. Blood samples for lipid and Lp(a measurements were taken in all the patients. Restenosis was defined as at least 50 % lumen narrowing of the coronary artery segment after angioplasty. Coronary atherosclerosis progression was established in cases of the new occlusion occurring, as well as identifying a 10 % decrease in lumen diameter in comparison with baseline angiograms.Results. Repeated coronary angiography revealed the signs of restenosis in 103 of 243 patients. Dividing patients into 3 groups according to the type of intervention demonstrated that the level of Lp(a (median 25–75 % quartiles was significantly higher in the restenosis group after implantation of BMS (33; 11–62 and 16; 6–39 mg/dl, respectively; p = 0.014 versus those who had undergone DES implantation (23; 10–30 and 20; 6–60 mg/dl; p = 0.7 or balloon angioplasty (17; 4–48 and 9; 4–36 mg/dl; p = 0.3. Patients with progression of coronary atherosclerosis had difference only in Lp(a levels compared to the group without progression (36; 13–62 versus 12; 4–26 mg/dl, p < 0,001.Conclusion. During the first year after elective PCI Lp(a concentration determined the severity of coronary atherosclerosis in non-culprit lesionsand associated with the risk of in

  2. Calcified Plaque of Coronary Artery: Factors Influencing Overestimation of Coronary Artery Stenosis on Coronary CT Angiography

    International Nuclear Information System (INIS)

    Kim, Mok Hee; Kim, Yun Hyeon; Choi, Song; Seon, Hyun