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https://www.readbyqxmd.com/read/27908689/pcsk9-genetic-variants-and-risk-of-type-2-diabetes-a-mendelian-randomisation-study
#1
Amand F Schmidt, Daniel I Swerdlow, Michael V Holmes, Riyaz S Patel, Zammy Fairhurst-Hunter, Donald M Lyall, Fernando Pires Hartwig, Bernardo Lessa Horta, Elina Hyppönen, Christine Power, Max Moldovan, Erik van Iperen, G Kees Hovingh, Ilja Demuth, Kristina Norman, Elisabeth Steinhagen-Thiessen, Juri Demuth, Lars Bertram, Tian Liu, Stefan Coassin, Johann Willeit, Stefan Kiechl, Karin Willeit, Dan Mason, John Wright, Richard Morris, Goya Wanamethee, Peter Whincup, Yoav Ben-Shlomo, Stela McLachlan, Jackie F Price, Mika Kivimaki, Catherine Welch, Adelaida Sanchez-Galvez, Pedro Marques-Vidal, Andrew Nicolaides, Andrie G Panayiotou, N Charlotte Onland-Moret, Yvonne T van der Schouw, Giuseppe Matullo, Giovanni Fiorito, Simonetta Guarrera, Carlotta Sacerdote, Nicholas J Wareham, Claudia Langenberg, Robert Scott, Jian'an Luan, Martin Bobak, Sofia Malyutina, Andrzej Pająk, Ruzena Kubinova, Abdonas Tamosiunas, Hynek Pikhart, Lise Lotte Nystrup Husemoen, Niels Grarup, Oluf Pedersen, Torben Hansen, Allan Linneberg, Kenneth Starup Simonsen, Jackie Cooper, Steve E Humphries, Murray Brilliant, Terrie Kitchner, Hakon Hakonarson, David S Carrell, Catherine A McCarty, H Lester Kirchner, Eric B Larson, David R Crosslin, Mariza de Andrade, Dan M Roden, Joshua C Denny, Cara Carty, Stephen Hancock, John Attia, Elizabeth Holliday, Martin O' Donnell, Salim Yusuf, Michael Chong, Guillaume Pare, Pim van der Harst, M Abdullah Said, Ruben N Eppinga, Niek Verweij, Harold Snieder, Tim Christen, Dennis O Mook-Kanamori, Stefan Gustafsson, Lars Lind, Erik Ingelsson, Raha Pazoki, Oscar Franco, Albert Hofman, Andre Uitterlinden, Abbas Dehghan, Alexander Teumer, Sebastian Baumeister, Marcus Dörr, Markus M Lerch, Uwe Völker, Henry Völzke, Joey Ward, Jill P Pell, Daniel J Smith, Tom Meade, Anke H Maitland-van der Zee, Ekaterina V Baranova, Robin Young, Ian Ford, Archie Campbell, Sandosh Padmanabhan, Michiel L Bots, Diederick E Grobbee, Philippe Froguel, Dorothée Thuillier, Beverley Balkau, Amélie Bonnefond, Bertrand Cariou, Melissa Smart, Yanchun Bao, Meena Kumari, Anubha Mahajan, Paul M Ridker, Daniel I Chasman, Alex P Reiner, Leslie A Lange, Marylyn D Ritchie, Folkert W Asselbergs, Juan-Pablo Casas, Brendan J Keating, David Preiss, Aroon D Hingorani, Naveed Sattar
BACKGROUND: Statin treatment and variants in the gene encoding HMG-CoA reductase are associated with reductions in both the concentration of LDL cholesterol and the risk of coronary heart disease, but also with modest hyperglycaemia, increased bodyweight, and modestly increased risk of type 2 diabetes, which in no way offsets their substantial benefits. We sought to investigate the associations of LDL cholesterol-lowering PCSK9 variants with type 2 diabetes and related biomarkers to gauge the likely effects of PCSK9 inhibitors on diabetes risk...
November 28, 2016: Lancet Diabetes & Endocrinology
https://www.readbyqxmd.com/read/27895023/pleiotropic-effects-of-pcsk9-proprotein-convertase-subtilisin-kexin-type-9-inhibitors
#2
Vera Bittner
No abstract text is available yet for this article.
November 29, 2016: Circulation
https://www.readbyqxmd.com/read/27878791/new-concepts-in-the-management-of-dyslipidaemiaa
#3
Baris Gencer, Nicolas Rodondi, Francois Mach
Recently, the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS) published a consensus paper giving guidance on the definition and management of statin-associated muscle symptoms (SAMS), as well as the use of proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors in very high-risk patients. The occurrence of SAMS can have a major negative impact on treatment adherence and, consequently, on the prognosis of cardiovascular diseases. In addition, both the ESC guidelines on the prevention of cardiovascular disease (CVD) in clinical practice with sections addressing global strategies to minimise the burden of CVD at population and individual levels, and the 2016 ESC/EAS guideline for the management of dyslipidaemias, focus on evaluation and treatment of SAMS...
2016: Swiss Medical Weekly
https://www.readbyqxmd.com/read/27877050/development-of-proprotein-convertase-subtilisin-kexin-type-9-inhibitors-and-the-clinical-potential-of-monoclonal-antibodies-in-the-management-of-lipid-disorders
#4
REVIEW
Sanjiv Gupta
The aim of this manuscript is to review available data to evaluate the present status of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in the treatment of hypercholesterolemia. Relevant literature since 2003 is reviewed. The effectiveness of PCSK9 inhibitors in lowering low-density lipoprotein cholesterol and other atherogenic lipid fractions was studied in various Phase 2 and Phase 3 trials of Alirocumab, Evolocumab, and Bococizumab. The results of published long-term ODYSSEY and OSLER studies are summarized...
2016: Vascular Health and Risk Management
https://www.readbyqxmd.com/read/27869438/immunology-update-biologics
#5
S Paul Starr
Biologics are substances made from a living organism or its products. These include genes, proteins (eg, antibodies, receptors, enzymes, inhibitors), recombinant proteins, and fusion proteins. Biologics often are produced using recombinant DNA technology. For example, monoclonal antibodies are produced by inserting human genes into immortalized cell cultures, which then produce the gene product (ie, an antibody) in large quantity. Another approach is to fuse genetic material from nonhuman sources (eg, mice) with human genetic material...
November 2016: FP Essentials
https://www.readbyqxmd.com/read/27865998/intensive-ldl-cholesterol-lowering-therapy-and-neurocognitive-function
#6
REVIEW
Maciej Banach, Manfredi Rizzo, Dragana Nikolic, George Howard, VirginiaJ Howard, DimitriP Mikhailidis
The key lipid-lowering target is to achieve guideline-recommended low-density lipoprotein cholesterol (LDL-C) levels, usually by using statins. The new treatment strategies for lipid-lowering therapy include using proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors as an exciting approach to reduce residual risk of cardiovascular diseases (CVD). However, concerns about possible adverse effects, including neurocognitive disorders, were issued by the Food and Drug Administration (FDA). The current disputable evidence does not allow definite conclusions as to whether statins contribute to, or cause, clinically meaningful cognitive impairment...
November 16, 2016: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27864787/glycaemic-effects-of-non-statin-lipid-lowering-therapies
#7
REVIEW
Patrick D Collins, Naveed Sattar
Since the publication of the JUPITER trial, attention has been focused on the adverse glycemic effects of statin therapy. Although the modest increase in the risk of new diabetes mellitus is outweighed by the reduction in cardiovascular events for statins, emerging biochemical and genetic links between lipid metabolism and glycemic control raise the prospect of a broader diabetogenic effect of lipid-lowering therapies. For the novel and powerful PCSK9-inhibitor class available evidence does not support a major glycaemic effect with the results of large scale trials awaited although preliminary genetic data does suggest a link...
December 2016: Current Cardiology Reports
https://www.readbyqxmd.com/read/27863217/eukaryotic-ribosome-as-a-target-for-cardiovascular-disease
#8
Simone Pellegrino, Gulnara Yusupova
Cardiovascular diseases have been associated with genetic variants and increased plasma level of the secreted protein PCSK9. In this issue of Cell Chemical Biology, Petersen et al. (2016) describe an inhibitor of PCSK9 secretion in human cells that, surprisingly, targets the 80S ribosome.
November 17, 2016: Cell Chemical Biology
https://www.readbyqxmd.com/read/27861116/pcsk9-inhibition-a-promise-fulfilled
#9
REVIEW
Khendi White, Chaitra Mohan, Michael Rocco
The association of reduced proprotein convertase subtilisin/kexin type 9 (PCSK9) activity with reduced cardiovascular disease (CVD) events--and the need for add-ons to statin therapy to achieve treatment goals--has led to the rapid development and US Food and Drug Administration (FDA) approval of monoclonal antibody therapies to inhibit PCSK9. Now that PCSK9 inhibitors are approved by the FDA for use in certain patients, data from ongoing long-term clinical trials addressing tolerability, safety, and proof of additional reduction in CVD events are eagerly awaited...
November 2016: Cleveland Clinic Journal of Medicine
https://www.readbyqxmd.com/read/27860267/a-phase-i-randomized-study-of-a-specifically-engineered-ph-sensitive-pcsk9-inhibitor-rn317-pf-05335810-in-hypercholesterolemic-subjects-on-statin-therapy
#10
M Levisetti, T Joh, H Wan, H Liang, P Forgues, B Gumbiner, P D Garzone
This phase I study assessed the safety, tolerability, pharmacokinetics, and pharmacodynamics of RN317 (PF-05335810), a specifically engineered, pH-sensitive, humanized proprotein convertase subtilisin kexin type 9 (PCSK9) monoclonal antibody, in hypercholesterolemic subjects (low-density lipoprotein cholesterol (LDL-C) ≥ 80 mg/dl) 18-70 years old receiving statin therapy. Subjects were randomized to: single-dose placebo, RN317 (subcutaneous (s.c.) 0.3, 1, 3, 6, or intravenous (i.v.) 1, 3, 6 mg/kg), or bococizumab (s...
November 17, 2016: Clinical and Translational Science
https://www.readbyqxmd.com/read/27846344/effect-of-evolocumab-on-progression-of-coronary-disease-in-statin-treated-patients-the-glagov-randomized-clinical-trial
#11
Stephen J Nicholls, Rishi Puri, Todd Anderson, Christie M Ballantyne, Leslie Cho, John J P Kastelein, Wolfgang Koenig, Ransi Somaratne, Helina Kassahun, Jingyuan Yang, Scott M Wasserman, Robert Scott, Imre Ungi, Jakub Podolec, Antonius Oude Ophuis, Jan H Cornel, Marilyn Borgman, Danielle M Brennan, Steven E Nissen
Importance: Reducing levels of low-density lipoprotein cholesterol (LDL-C) with intensive statin therapy reduces progression of coronary atherosclerosis in proportion to achieved LDL-C levels. Proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors produce incremental LDL-C lowering in statin-treated patients; however, the effects of these drugs on coronary atherosclerosis have not been evaluated. Objective: To determine the effects of PCSK9 inhibition with evolocumab on progression of coronary atherosclerosis in statin-treated patients...
November 15, 2016: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/27844136/-ecs-guidelines-2016-dyslipidaemias
#12
D Sinning, U Landmesser
Dyslipidaemia is a major cause of atherosclerotic cardiovascular disease and its progression towards clinical complications, such as acute coronary syndromes and stroke. In August 2016 the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS) issued new joint guidelines for the management of dyslipidaemias. In these new guidelines, the concept of treating patients to a risk-based low-density lipoprotein (LDL) cholesterol target is reinforced. The task force considers LDL cholesterol as the primary target for dyslipidaemia treatment, whereas high-density lipoprotein (HDL) cholesterol is not recommended as a treatment target (based on the failure of HDL cholesterol elevation treatment strategies to reduce cardiovascular risk in recent studies)...
December 2016: Herz
https://www.readbyqxmd.com/read/27796655/retrograde-cholesterol-transport-in-the-human-caco-2-tc7-cell-line-a-model-to-study-trans-intestinal-cholesterol-excretion-in-atherogenic-and-diabetic-dyslipidemia
#13
Camille Dugardin, Olivier Briand, Véronique Touche, Marleen Schonewille, François Moreau, Cédric Le May, Albert K Groen, Bart Staels, Sophie Lestavel
AIMS: The dyslipidemia associated with type 2 diabetes is a major risk factor for the development of atherosclerosis. Trans-intestinal cholesterol excretion (TICE) has recently been shown to contribute, together with the classical hepatobiliary route, to fecal cholesterol excretion and cholesterol homeostasis. The aim of this study was to develop an in vitro cell model to investigate enterocyte-related processes of TICE. METHODS: Differentiated Caco-2/TC7 cells were grown on transwells and incubated basolaterally (blood side) with human plasma and apically (luminal side) with lipid micelles...
October 28, 2016: Acta Diabetologica
https://www.readbyqxmd.com/read/27789928/pcsk9-inhibitors-clinical-applications
#14
REVIEW
Robert Schmidli
No abstract text is available yet for this article.
October 2016: Australian Prescriber
https://www.readbyqxmd.com/read/27789927/pcsk9-inhibitors-mechanisms-of-action
#15
REVIEW
Michael M Page, Gerald F Watts
No abstract text is available yet for this article.
October 2016: Australian Prescriber
https://www.readbyqxmd.com/read/27785114/lipoprotein-apheresis-in-the-management-of-severe-hypercholesterolemia-and-of-elevation-of-lipoprotein-a-current-perspectives-and-patient-selection
#16
REVIEW
Ulrich Julius
This review reports the current situation with respect to therapeutic options (lifestyle and drugs) reducing the concentrations of atherogenic low-density lipoprotein cholesterol (LDL-C) and lipoprotein(a) (Lp[a]). Three lipoprotein apheresis (LA) principles have been realized: precipitation, filtration, and adsorption. Available LA methods are herein described in detail - major components, pumps, extracorporeal volume, treated volume, and anticoagulation. General features of all LA methods as well as pleotropic effects are elaborated...
2016: Medical Devices: Evidence and Research
https://www.readbyqxmd.com/read/27758865/an-unbiased-mass-spectrometry-approach-identifies-glypican-3-as-an-interactor-of-proprotein-convertase-subtilisin-kexin-type-9-pcsk9-and-low-density-lipoprotein-receptor-ldlr-in-hepatocellular-carcinoma-cells
#17
Kévin Ly, Rachid Essalmani, Roxane Desjardins, Nabil G Seidah, Robert Day
The mechanism of LDL receptor (LDLR) degradation mediated by the proprotein convertase subtilisin/kexin type 9 (PCSK9) has been extensively studied; however, many steps within this process remain unclear and still require characterization. Recent studies have shown that PCSK9 lacking its Cys/His-rich domain can still promote LDLR internalization, but the complex does not reach the lysosome suggesting the presence of an additional interaction partner(s). In this study we carried out an unbiased screening approach to identify PCSK9-interacting proteins in the HepG2 cells' secretome using co-immunoprecipitation combined with mass spectrometry analyses...
November 18, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27755114/proprotein-convertase-subtilisin-kexin-type-9-inhibitors-update-from-clinical-trials-to-real-world-experience
#18
Michel Farnier
PURPOSE OF REVIEW: After the approval of alirocumab and evolocumab, the first two monoclonal antibodies (mAbs) targeting proprotein convertase subtilisin kexin type 9 (PCSK9), this review provides an update on recent PCSK9 inhibitors data and describes recommendations for the use before the results of the ongoing cardiovascular endpoint trials. RECENT FINDINGS: New studies and complementary analysis of phase III trials have consistently shown that alirocumab and evolocumab are highly effective in reducing LDL-cholesterol and to some extent lipoprotein (a)...
December 2016: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/27753273/abstracts
#19
Bernd Hohenstein
As a major event in the field of therapeutic apheresis, lipidology and immune-modulating extracorporeal treatments, Dresden hosted the 4(th) International Symposium on Therapeutic Apheresis 17-19 March 2016. In conjunction with the newly founded European Group - International Society for Apheresis, this meeting attracted more than 300 clinicians and scientists from more than a dozen European countries and further developed into an important event for participants, industry and nursing staff. Due to the relevant role of lipoprotein apheresis in Germany and the recent launch of PCSK9 inhibitors corresponding sessions, the symposium reflected all aspects of this new lipidological therapy in a number of sessions...
October 2016: Therapeutic Apheresis and Dialysis
https://www.readbyqxmd.com/read/27751895/proprotein-convertase-subtilisin-kexin-type-9-inhibitors-a-brief-overview
#20
REVIEW
Zachary R Noel, Craig J Beavers
Proprotein convertase subtilisin/kexin type 9 inhibitors serve as a valuable addition to the armamentarium of lipid-lowering agents and have promising potential. By inhibiting the proprotein convertase subtilisin/kexin type 9 enzyme, this novel molecule leads to increased low-density lipoprotein receptor density and decreased circulation of low-density lipoprotein. The fact the agent is a monoclonal antibody has led to limited drug interactions and minimized adverse drug events. It is critical for all providers to have a basic understanding of these novel therapies with their introduction and use for treatment...
October 15, 2016: American Journal of Medicine
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