*  Cordis Announces Discontinuation of NEVOâ„¢ Sirolimus-Eluting Coronary Stent
BRIDGEWATER, N.J., June 15, 2011 /PRNewswire-FirstCall/ -- Cordis Corporation, a worldwide leader in the development and manufacture of interventional vascular technology, today announced it will no longer pursue the development of the NEVO™ Sirolimus-Eluting Coronary Stent in order to focus on other cardiovascular therapies where significant patient need exists. The company will also stop the manufacture of CYPHER® and CYPHER SELECT® Plus Sirolimus-Eluting Coronary Stents by the end of 2011.. "Due to evolving market dynamics in the drug-eluting stent (DES) business, we see greater opportunities to benefit patients and grow our business in other areas of the cardiovascular device market," said Seth Fischer, Company Group Chair and Worldwide Chairman, Cordis Corporation. "Cordis has been a leader in establishing many markets including diagnostic and guiding catheters, bare metal and drug-eluting stents, ...
  https://www.mdtmag.com/news/2011/06/cordis-announces-discontinuation-nevo%C3%A2%E2%80%9E%C2%A2-sirolimus-eluting-coronary-stent
*  Randomized Study Comparing Endeavor With Cypher Stents (PROTECT) - Full Text View - ClinicalTrials.gov
The PROTECT TRIAL is a randomized stent trial with 8800 patients in approximately 200 hospitals, which is designed to evaluate whether the Endeavor stent PROTECTS against late stent thrombosis resulting in less deaths and myocardial infarctions.. Study Stents:. Medtronic Endeavor® Zotarolimus Eluting Coronary Stent System or next generation model Cordis Cypher® Sirolimus-eluting Coronary Stent, Cordis Cypher Select® Sirolimus-eluting Coronary Stent or next generation model. Primary Objective: To compare overall stent thrombosis rate of the Endeavor® Zotarolimus Eluting Coronary Stent System versus the Cypher® Sirolimus-eluting Coronary Stent in a patient population requiring stent implantation. Secondary Objective: To compare the composite endpoint of total death or cardiac ...
  https://clinicaltrials.gov/ct2/show/NCT00476957?term=heart+attack&lup_s=04%2F22%2F2013&lup_d=14&show_rss=Y&sel_rss=mod14
*  Optimal Duration of DAPT Following Treatment With Endeavor (Zotarolimus-eluting Stent) in Real-world Japanese Patients - Full...
A prospective multicenter registry in real-world Japanese patients undergoing DAPT for three months after stenting. To assess the long-term safety of Endeavor Zotarolimus-eluting stent through noninferiority in the primary endpoint between two different continuous regimen (three and twelve months) groups of DAPT after stenting with Endeavor Zotarolimus-eluting stent in real-world Japanese patients and to examine the optimal duration of DAPT after stenting with Endeavor Zotarolimus-eluting stent. The long-term DAPT group in the present clinical study (to be appropriated from the post-marketing surveillance of Endeavor) should consist of consecutive patients undergoing DAPT for twelve months after stenting, while the short-term DAPT group (to be newly registered in the present clinical study) should consist of patients who are instructed to undergo DAPT for three months after ...
  https://clinicaltrials.gov/ct2/show/NCT01325935?term=Cerebral+Arteriosclerosis&rank=10
*  Patent US5985890 - Rapamycin derivatives - Google Patents
Rapamycin derivatives selected among 32(S)-dihydro-rapamycin derivatives and 32-deoxo-rapamycin compounds. Rapamycin derivatives are disclosed of the formula: ##STR1## wherein the variables are in the specification.
  http://www.google.com/patents/US5985890?dq=5920316
*  JNJ) Johnson & Johnson to Discontinue Cypher Stent
Cordis Corporation, a Johnson & Johnson (JNJ) company, recently announced that it will stop manufacturing Cypher and Cypher Select Plus sirolimus-eluting coronary stents by year end.. The company will also discontinue the development of Nevo sirolimus-eluting coronary stent. Cordis intends to focus on other cardiovascular therapies instead.. Cypher Sales Were Under Pressure. The decision to discontinue Cypher stent does not come as a surprise given the declining sales of the product. Changing dynamics in the drug-eluting stent (DES) market along with unlicensed competition from products infringing Cordis' patents led to an erosion in Cypher stent's pricing, sales and market share. Moreover, the launch of superior products by competitors also led to a loss of market share.. On the first quarter call, Johnson & Johnson reported a 41% decline in Cypher sales with worldwide share declining to ...
  http://www.stockbloghub.com/2011/06/16/jnj-johnson-johnson-to-discontinue-cypher-stent/76575
*  Sirolimus-Eluting Coronary Stents in Octogenarians | JACC: Cardiovascular Interventions
Several observations were made in this subanalysis of the e-SELECT registry. First, the prevalence of concomitant disorders was significantly higher in octogenarians than in the younger study group, and the Charlson comorbidity index was the most powerful predictor of death and stent thrombosis in octogenarians. Second, the rates of death, MI, stent thrombosis, and major bleeding were all higher in octogenarians, an observation reflecting the higher overall risk represented by aging. Third, no definite or probable stent thrombosis occurred beyond 6 months of follow-up in octogenarians, despite a significantly lower use of dual antiplatelet therapy at 1 year compared with younger patients. Finally, the need for repeat revascularization was similar in both groups.. Stent thrombosis is the most feared complication of DES implantation. Although the incidence of acute stent thrombosis was similar in both study groups, subacute ...
  http://interventions.onlinejacc.org/content/4/9/982
*  Preliminary Results of the Hydroxyapatite Nonpolymer-Based Sirolimus-Eluting Stent for the Treatment of Single De Novo Coronary...
The main finding of this first-in-human study with the non-polymer-based VES is that sirolimus can be efficiently delivered to the coronary artery without a durable polymer, as demonstrated by the minimum neointimal growth noted at QCA and IVUS.. The development of novel DES systems must be guided by 2 main rationales: 1) to achieve an improved safety profile, and 2) to improve or at least keep the efficacy profile at levels comparable to those of the existing DES devices.. The DES toxicity may be related mainly to 2 aspects: dose/type of the antiproliferative agent delivered to the coronary artery and presence/type of polymer used to carry the antiproliferative drug. In this context, the novel VES carries less than one-half of the dose of the first-generation Cypher sirolimus-eluting stent. As previously demonstrated by Nakamura et al. (22), it is possible to keep the same efficacy of the Cypher stent using 70% or even 45% of its original ...
  http://interventions.onlinejacc.org/content/1/5/545
*  Randomized, Double-Blind, Placebo-Controlled Trial of Oral Sirolimus for Restenosis Prevention in Patients With In-Stent...
This randomized, double-blind, and placebo-controlled trial was performed to assess the impact of an oral, short-term administration of sirolimus for the prevention of restenosis after PCI in patients at high risk for recurrent restenosis. The trial demonstrates that short-term administration of sirolimus over a total of 10 days, including 2 days with an intensified loading dose before the intervention, results in a significant reduction of angiographic restenosis after treatment of ISR. Furthermore, the study reveals a significant correlation of the sirolimus blood level at the time of intervention with late lumen loss at follow-up.. Sirolimus, a macrolide immunosuppressant with anti-inflammatory and antiproliferative capacities, is a fermentation product of Streptomyces hygroscopicus.11 The proposed mechanism of the antiproliferative effect of sirolimus is based on its ability to bind to its intracellular receptor, the ...
  http://circ.ahajournals.org/content/110/7/790
*  Hybrid Sirolimus-Eluting Stents with Biodegradable Polymer did not Improve Angiographic Outcomes Compared to Everolimus-Eluting...
Results from the PRISON IV Trial Presented at TCT 2016 and Simultaneously Published in JACC: Cardiovascular Interventions. WASHINGTON - November 2, 2016 - Results from a randomized, multicenter trial failed to show non-inferiority of hybrid, ultra-thin strut sirolimus-eluting stents (Osiro SES) with a biodegradable polymer compared to thin-strut everolimus-eluting stents (Xience EES) with a durable polymer in terms of in-segment late lumen loss in successfully treated chronic total occlusions. In addition, although the rate of binary restenosis was low overall in this complex lesion subset, it was higher with the Osirio SES compared with the Xience EES.. Findings from the PRISON IV trial were reported today at the 28th annual Transcatheter Cardiovascular Therapeutics (TCT) scientific symposium. Sponsored by the Cardiovascular Research Foundation (CRF), TCT is the world's premier educational meeting specializing in interventional cardiovascular medicine. The ...
  http://www.crf.org/crf/news-and-events/news/news/1866-hybrid-sirolimus-eluting-stents-with-biodegradable-polymer-did-not-improve-angiographic-outcomes-compared-to-everolimus-eluting-stents-with-durable-polymer
*  Abstract 4916: Difference in Neointimal Growth on the Stent Struts Crossing a Side Branch Between Sirolimus-Eluting Stent and...
Background: A bifurcation lesion has been demonstrated to be the high risk lesion for late stent thrombosis (LST) following drug-eluting stent implantation, resulting from disturbed laminar blood flow and delayed endothelialization of unapposed stent struts. We examined differences in neointimal growth on the stent struts crossing a side branch between sirolimus-eluting stent (SES) and bare-metal stent (BMS) using optical coherence tomography (OCT)... Methods and Results: Of the 41 stents (34 cases) implanted across side branches, 70 struts of 28 SES and 23 struts of 13 BMS, which crossed over a side branch, were analyzed 9 months after stent implantation using OCT. Ten of 28 SES were also analyzed after 3 months. Neointimal growth around the unapposed struts, extending from the adjacent vessel wall, was classified into either complete or incomplete coverage ...
  http://circ.ahajournals.org/content/118/Suppl_18/S_960.1
*  lymphedema from sirolimus treatment [Lymphedema People]
Journal of Drugs in Dermatology, March, 2006 by Lindsey Warino, James Libecco Abstract Cancer is a major cause of death in immunosuppressed transplant patients. Therefore, sirolimus is frequently used in these patients for its immunosuppressive and antineoplastic properties. However, a variety of cutaneous side effects have resulted from sirolimus therapy. Consequently, dermatologists must be aware of such adverse events and understand the risks and benefits of discontinuing therapy. Introduction Sirolimus (Rapamycin) is an immunosuppressive agent often used in combination with cyclosporine and corticosteroids in renal transplant patients. In contrast to the calcineurin inhibitors, sirolimus, a macrocyclic lactone isolated from Streptomyces Hygroscopicus, has no effect on calcineurin activity. (1-15) Rather, it acts to suppress cytokine-driven T cell proliferation and inhibits the progression from G1 to the S phase of the cell cycle. Not ...
  http://www.lymphedemapeople.com/wiki/doku.php?id=lymphedema_from_sirolimus_treatment
*  A Study of mTOR Inhibitor Everolimus (RAD001) in Association With Cisplatin and Radiotherapy for Locally Advanced Cervix Cancer...
The cervix cancer is the second malignant neoplasia more common between women. The combined treatment involving chemotherapy and radiotherapy was defined as the standard. This study will evaluate the safety, toxicity and maximal tolerated dose (MTD) of everolimus in association with cisplatin and pelvic radiotherapy, in patients with squamous cells carcinoma of uterine cervix, in stages IIB and IIIB ...
  https://clinicaltrials.gov/ct2/show/record/NCT01217177
*  Abstract 2159: Medial Necrosis Due to Sirolimus-Eluting Stent Implantation in Human Coronary Arteries | Circulation
Background: Sirolimus-eluting stents (SES) have been proven to reduce the rates of restenosis by a striking inhibition of neointimal hyperplasia. However, unusual vessel responses to SES, such as late-acquired incomplete stent apposition (ISA) have been observed, and the precise mechanism of late ISA has not been clarified.. Methods and Results: To examine the mechanism of late ISA, the temporal mode of vascular responses after SES (3 days (D) to 12 months (M), 14 lesions) and bare metal stent (BMS; 2 D to 12 M, 24 lesions) implantation was investigated histopathologically in necropsied coronary arteries. In arteries that had been implanted with SES for 4 M, the stent struts were focally covered by thin membranous tissue mainly composed of fibrin deposition. Complete coverage of BMS by neointimal tissue composed of smooth muscle cells (SMC) and extracellular matrix (ECM) was documented after 1.5 M. Only mild neointimal ...
  http://circ.ahajournals.org/content/116/Suppl_16/II_468.3
*  Phase 1 Trial of the Mammalian Target of Rapamycin (mTOR) Inhibitor Everolimus Plus Radiation Therapy (RT) for Salvage...
This is a Phase 1 dose escalation study of an investigational agent, everolimus, given in combination with standard radiation therapy, in prostate cancers with a rising PSA following a prostatectomy. A maximum of 33 people will be enrolled on this study at the University of Pennsylvania. The primary objective of this study is to determine the acute and chronic toxicities and maximum tolerated dose of everolimus with concurrent radiation ...
  https://clinicaltrials.gov/show/NCT01548807
*  Studies show everolimus-eluting stent implantation reduces restenosis and repeat revasculariztion
Additionally, no patient in the calcified group suffered from stent thrombosis up to 3 years after PCI, while two thrombotic complications occurred in the noncalcified group. Although large population studies with long-term follow-up are mandatory, the authors concluded that EES implantation for calcified culprit lesions appears to be safe up to 3 years. This study also demonstrated that the rates of in-stent ABR (4.3%) and ID-TLR (5.9%) at 6 months for calcified culprit lesions are remarkably lower than that in previous BMS studies, in which these rates ranged from 12 to 23% and from 18 to 23%, respectively, suggesting that EES implantation is more effective for calcified culprit lesions than BMS implantation ...
  http://www.rxpgnews.com/research/Studies-show-everolimus-eluting-stent-implantation-reduces-restenosis-and-repeat-revasculariztion_436074.shtml
*  China Sirolimus Eluting Coronary Stent - China Sirolimus Eluting Coronary Stent, Drug Eluting Stent
China Sirolimus Eluting Coronary Stent, Find details about China Sirolimus Eluting Coronary Stent, Drug Eluting Stent from Sirolimus Eluting Coronary Stent - Yilson Medical Technology Co., Ltd.
  http://yilson.en.made-in-china.com/product/zqBQYwIlrehy/China-Sirolimus-Eluting-Coronary-Stent.html
*  The Representative Porcine Model for Human Cardiovascular Disease : Figure 5
Figure 5: (a) X-rays of longitudinally cut rabbit iliac arteries at 21 days after placement of overlapping ZES, SES, and PES. The extent of stent coverage by endothelial cells was greatest with ZES, with almost complete coverage in the proximal and distal segments and significantly greater coverage in the overlapped segment compared with SES and PES. (b) Photomicrographs showing the amount of neointimal thickness at 28 days after placement of Endeavor zotarolimus-eluting stents (ZESs), Cypher sirolimus-eluting stents (SESs), Taxus paclitaxel-eluting stents (PESs), and Driver bare metal stents (BMSs) in rabbit iliac arteries. With SES, there were focally uncovered stent struts, which were associated with inflammation consisting of heterophils or eosinophils and giant cells. Adapted from [49 ...
  https://www.hindawi.com/journals/bmri/2011/195483/fig5/
*  A retrospective review of oral low-dose sirolimus (rapamycin) for the treatment of active uveitis | Journal of Ophthalmic...
Sirolimus is a unique and potent agent with broad anti-inflammatory and immunomodulatory activities. Early studies suggest sirolimus may have many diverse roles, including treating patients with retinal thickening secondary to leakage as in neovascular age-related macular degeneration and diabetic macular edema [9]. Sirolimus inhibits the translation and activity of hypoxia-inducible factor-1 alpha (HIF-1a), a stress-activated protein that is a potent stimulator of vascular endothelial growth factor (VEGF), and its inhibition affects VEGF both upstream at the production level and downstream at the receptor level [10]. This inhibition is a direct effect on the endothelial barrier, independent of vasodilation, and plays an important role in angiogenesis and hyperpermeability [11]. A study showed that sirolimus was superior to VEGF inhibition in a co-culture assay of endothelial cells (EC) and retinal pigment epithelium (RPE) by reducing EC ...
  https://joii-journal.springeropen.com/articles/10.1007/s12348-010-0015-5
*  Plus it
Purpose: Mammalian target of rapamycin (mTOR) inhibitors mediate AKT activation through a type 1 insulin-like growth factor receptor (IGF-1R)-dependent mechanism. Combining the mTOR inhibitor temsirolimus with cixutumumab, a fully human IgG1 monoclonal antibody directed against IGF-1R, was expected to enhance mTOR-targeted anticancer activity by modulating resistance to mTOR inhibition. Objectives of this Phase I study were to evaluate the tolerability and activity of temsirolimus and cixutumumab. Experimental Design: Patients in sequential cohorts ("3+3" design) received escalating doses of temsirolimus with cixutumumab weekly for 28 days. At MTD, 21 patients were randomized into three separate drug sequence treatment groups for serial blood draws and FDG-PET/CT scans for pharmacodynamic analyses (PD). Results: Forty-two patients with advanced cancer (19M/23F, median age = 53, median number of prior therapies = 4) were enrolled. MTD was reached at ...
  http://clincancerres.aacrjournals.org/content/early/2011/07/12/1078-0432.CCR-10-2979
*  RTOG 0913: A Phase 1 Study of Daily Everolimus (RAD001) in Combination With Radiation Therapy and Temozolomide in Patients With...
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 ...
  https://www.osti.gov/scitech/biblio/22267831-rtog-phase-study-daily-everolimus-rad001-combination-radiation-therapy-temozolomide-patients-newly-diagnosed-glioblastoma
*  Abstract 18208: Prospective and Systematic Analysis of Unexpected Requests for Non-cardiac Surgery or Invasive Procedures...
Background: No sufficient data exists regarding prevalence, timing and clinical outcomes of unexpected requests for non-cardiac surgery or invasive procedures during the first year after drug-eluting stents (DESs) implantation. Methods and Results: We randomly assigned 2,117 patients with coronary artery stenosis into two groups according to dual antiplatelet therapy (DAPT) duration and stent type; 3-month DAPT following Endeavor zotarolimus-eluting stent (E-ZES) implantation (E-ZES+3-month DAPT, n=1,059) vs. 12-month DAPT following the other DES implantation (standard therapy, n=1,058). We prospectively investigated the prevalence, timing and clinical outcomes of unexpected requests for non-cardiac surgery or invasive procedures during the first year after DESs implantation between the two groups. The prevalence of requested non-cardiac surgery or invasive procedures was 14.6% (310 requests in 261 patients). Among 310 requests, those were proposed in 11.3% ...
  http://circ.ahajournals.org/content/126/Suppl_21/A18208
*  Right coronary artery 'diverticulosis' 4 years after sirolimus-eluting stent implantation associated with very late stent...
If patients could recognise themselves, or anyone else could recognise a patient from your description, please obtain the patient's written consent to publication and send them to the editorial office before submitting your response [Patient consent forms] ...
  http://heart.bmj.com/content/99/21/1627.responses