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https://www.readbyqxmd.com/read/28060539/bococizumab-for-the-treatment-of-hypercholesterolaemia
#1
Nicola Ferri, Alberto Corsini, Cesare R Sirtori, Massimiliano Ruscica
Low-density lipoprotein cholesterol (LDL-C) remains a well-established risk factor for cardiovascular disease (CVD). LDL-C levels are considered primary targets of therapy. A new series of systemic biomolecules, the monoclonal antibodies (mAbs) of proprotein convertase subtilisin/kexin type 9 (PCSK9), have a higher activity in reducing LDL-C. Areas Covered: The authors critically review the current evidence on the efficacy and safety of bococizumab, a humanized mAb against PCSK9, which was surprisingly discontinued in November 2016...
January 6, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28038950/pcsk9-inhibitors-in-the-current-management-of-atherosclerosis
#2
Thomas F Whayne
The history of proprotein convertase subtilisin/kexin type 9 (PCSK9) in medical science is fascinating and the evolution of knowledge of its function has resulted in new medications of major importance for the cardiovascular (CV) patient. PCSK9 functions as a negative control or feedback for the cell surface receptors for low-density lipoprotein including its component of cholesterol (LDL-C). The initial and key findings were that different abnormalities of PCSK9 can result in an increase or a decrease of LDL-C because of more or less suppression of cell surface receptors...
December 27, 2016: Archivos de Cardiología de México
https://www.readbyqxmd.com/read/28025677/pcsk9-inhibition-the-dawn-of-a-new-age-in-cholesterol-lowering
#3
REVIEW
David Preiss, Marion Mafham
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a circulating enzyme of hepatic origin that plays a key role in LDL receptor turnover. Genetic studies have confirmed that individuals with gain-of-function PCSK9 mutations have increased PCSK9 activity, elevated LDL-cholesterol levels and a severe form of familial hypercholesterolaemia. Those with variants leading to reduced PCSK9 have lower LDL-cholesterol levels and a reduced risk of coronary heart disease, and this has led to the development of various strategies aimed at reducing circulating PCSK9...
December 26, 2016: Diabetologia
https://www.readbyqxmd.com/read/27993383/old-challenges-and-new-opportunities-in-the-clinical-management-of-heterozygous-familial-hypercholesterolemia-hefh-the-promises-of-pcsk9-inhibitors
#4
REVIEW
Marcello Arca
Heterozygous familial hypercholesterolemia (HeFH) is a common (early estimates suggested a prevalence of 1 in 500 individuals, but recent studies have indicated that it may be higher) genetic disorder characterized by markedly elevated plasma concentrations of low-density lipoprotein cholesterol (LDL-C). HeFH is associated with an elevated risk of premature coronary heart disease, stroke, and peripheral vascular disease. Despite the availability of reliable diagnostic criteria (high LDL-C levels, family history or premature CHD and hypercholesterolemia, cerebral/peripheral vascular disease, and the presence of tendon xanthomata or presence of arcus cornealis before age of 45), HeFH is underdiagnosed and undertreated worldwide...
September 2, 2016: Atherosclerosis
https://www.readbyqxmd.com/read/27972090/low-density-lipoprotein-cholesterol-lowering-efficacy-of-evolocumab-may-reduce-need-for-apheresis-in-heterozygous-familial-hypercholesterolaemia-patients-according-to-russian-guidelines
#5
T D Gonzalez, A Kurylev, A Kolbin, T Zinina, E Sidelnikov, G Villa
No abstract text is available yet for this article.
November 2016: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
https://www.readbyqxmd.com/read/27972072/cost-effectiveness-of-evolocumab-in-patients-with-high-cardiovascular-risk-in-spain
#6
G Villa, M Lothgren, L Kutikova, P Lindgren, S R Gandra, G C Fonarow, F Sorio, L Masana, A Bayes-Genis, B van Hout
No abstract text is available yet for this article.
November 2016: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
https://www.readbyqxmd.com/read/27941065/factorial-effects-of-evolocumab-and-atorvastatin-on-lipoprotein-metabolism
#7
Gerald F Watts, Dick C Chan, Ricardo E Dent, Ransi Somaratne, Scott M Wasserman, Rob Scott, Sally Burrows, Peter Hugh R Barrett
BACKGROUND: -Monoclonal antibodies (mAbs) against proprotein convertase subtilisin kexin type 9 (PCSK9), such as evolocumab, lower plasma low-density lipoprotein (LDL)-cholesterol concentrations. Evolocumab is under investigation for its effects on cardiovascular outcomes in statin-treated, high-risk patients. The mechanism of action of PCSK9 mAbs on lipoprotein metabolism remains to be fully evaluated. Stable isotope tracer kinetics can effectively elucidate the mode of action of new lipid regulating pharmacotherapies...
December 9, 2016: Circulation
https://www.readbyqxmd.com/read/27929280/evolocumab-repatha-for-the-treatment-of-hyperlipidemia
#8
Deborah R Erlich
No abstract text is available yet for this article.
November 15, 2016: American Family Physician
https://www.readbyqxmd.com/read/27919366/ldl-apheresis-activates-the-complement-system-and-the-cytokine-network-whereas-pcsk9-inhibition-with-evolocumab-induces-no-inflammatory-response
#9
Knut Tore Lappegård, Terje Enebakk, Hilde Thunhaug, Judith Krey Ludviksen, Tom Eirik Mollnes, Anders Hovland
BACKGROUND: Low-density lipoprotein (LDL) apheresis is an extracorporeal treatment modality used in high-risk coronary patients. It may, however, induce complement activation and downstream inflammation due to bio-incompatibility. OBJECTIVE: We explored changes in soluble inflammatory markers when changing from LDL apheresis to the novel PCSK9 inhibitor evolocumab. METHODS: Three patients with familial hypercholesterolemia participated. Blood samples (EDTA plasma) for complement activation and markers of inflammation were obtained before (baseline) and after LDL apheresis week at 0 and before biweekly administration of evolocumab at weeks 1, 3, 5, and 7...
November 2016: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/27888902/-unmet-needs-patients-with-statin-intolerance-or-familial-hypercholesterolemia
#10
Luis Masana, Fernando Civeira
The achievement of low-density lipoprotein (LDL) therapeutic targets is especially difficult in some patients at high cardiovascular risk. These patients include persons with statin intolerance and those with very high LDL cholesterol (LDLc) levels such as persons with familial hypercholesterolemia. The proportion of statin-intolerant patients is between 7% and 29%. Alternative lipid-lowering drugs (including ezetimibe) are less effective and are not free from adverse effects. Both alirocumab, with the ODYSSEY ALTERNATIVE study, and evolocumab, with the GAUSS study, have shown strong lipid-lowering efficacy, with much greater tolerability than currently available alternatives, with the result that a larger number of patients achieve therapeutic targets...
May 2016: Clínica e Investigación en Arteriosclerosis
https://www.readbyqxmd.com/read/27882214/efficacy-and-safety-of-different-doses-of-evolocumab-in-reducing-low-density-lipoprotein-cholesterol-levels-a-meta-analysis
#11
Cheng Cheng, Sijia Sun, Yafeng Zhou, Xiangjun Yang
Evolocumab has been considered as an efficacious, safe and promising therapeutic modality for hypercholesterolemia and is associated with cardiovascular diseases. The efficacy and safety of two different doses of evolocumab were evaluated and the safety of evolocumab was compared with that of a placebo and ezetimibe. PubMed and EMBASE databases were searched and randomized controlled trials that examined the effect and safety of evolomucab compared with a placebo and ezetimibe were retrieved. Two authors independently performed article reviews and study quality evaluations...
November 2016: Biomedical Reports
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
#12
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/27861991/impact-of-target-mediated-elimination-on-the-dose-and-regimen-of-evolocumab-a-human-monoclonal-antibody-against-proprotein-convertase-subtilisin-kexin-type-9-pcsk9
#13
John P Gibbs, Sameer Doshi, Mita Kuchimanchi, Anita Grover, Maurice G Emery, Michael G Dodds, Megan A Gibbs, Ransi Somaratne, Scott M Wasserman, Dirk Blom
Understanding the pharmacokinetic (PK) and pharmacodynamic (PD) relationship of a therapeutic monoclonal antibody against proprotein convertase subtilisin/kexin type 9 (PCSK9) exhibiting target-mediated drug disposition (TMDD) is critical for selecting optimal dosing regimens. We describe the PK/PD relationship of evolocumab using a mathematical model that captures evolocumab binding and removal of unbound PCSK9 as well as reduction in circulating low-density lipoprotein cholesterol (LDL-C). Data were pooled from 2 clinical studies: a single-dose escalation study in healthy subjects (7-420 mg SC; n = 44) and a multiple-dose escalation study in statin-treated hypercholesterolemic patients (14 mg weekly to 420 mg monthly [QM] SC; n = 57)...
November 15, 2016: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/27848220/evolocumab-for-treating-primary-hypercholesterolaemia-and-mixed-dyslipidaemia-an-evidence-review-group-perspective-of-a-nice-single-technology-appraisal
#14
REVIEW
Christopher Carroll, Paul Tappenden, Rachid Rafia, Jean Hamilton, Duncan Chambers, Mark Clowes, Paul Durrington, Nadeem Qureshi, Anthony S Wierzbicki
As part of its Single Technology Appraisal (STA) process, the National Institute for Health and Care Excellence (NICE) invited the manufacturer of evolocumab (Amgen) to submit evidence on the clinical and cost effectiveness of evolocumab. The appraisal assessed evolocumab as monotherapy or in combination with a statin (HMG-CoA reductase inhibitor) with or without ezetimibe, or in combination with ezetimibe (without statin therapy), in adult patients with primary hypercholesterolaemia (which includes mixed dyslipidaemia), for whom statins do not provide optimal control of their low-density lipoprotein cholesterol (LDL-C) levels and/or for whom statins are contraindicated or not tolerated...
November 16, 2016: PharmacoEconomics
https://www.readbyqxmd.com/read/27846344/effect-of-evolocumab-on-progression-of-coronary-disease-in-statin-treated-patients-the-glagov-randomized-clinical-trial
#15
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...
13, 2016: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/27830381/cardiovascular-safety-of-evolocumab-a-systematic-review-and-meta-analysis
#16
EDITORIAL
Chayakrit Krittanawong, Takeshi Kitai, HongJu Zhang, Tao Sun
No abstract text is available yet for this article.
December 2016: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/27797643/modern-management-of-familial-hypercholesterolemia
#17
P Barton Duell, Ishwarlal Jialal
Familial hypercholesterolemia (FH) is a common genetic disorder that can manifest clinically as both the severe homozygous (HoFH) form that often presents in childhood and the commoner heterozygous (HeFH) form that is typically identified in adults. The majority of genetic causes are due to defects in low-density lipoprotein (LDL) receptor synthesis and action. Until recently, it was exceedingly difficult to achieve the goal of a 50% reduction in LDL-cholesterol or LDL-C < 70-100 in these patients. Established therapies include statins, niacin, bile-acid sequestrants, and ezetimibe in various combinations...
December 2016: Metabolic Syndrome and related Disorders
https://www.readbyqxmd.com/read/27789931/evolocumab
#18
REVIEW
(no author information available yet)
No abstract text is available yet for this article.
October 2016: Australian Prescriber
https://www.readbyqxmd.com/read/27755114/proprotein-convertase-subtilisin-kexin-type-9-inhibitors-update-from-clinical-trials-to-real-world-experience
#19
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/27739167/very-low-ldl-c-levels-may-safely-provide-additional-clinical-cardiovascular-benefit-the-evidence-to-date
#20
REVIEW
Terry McCormack, Ricardo Dent, Mark Blagden
BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death in Europe and increased low-density lipoprotein cholesterol (LDL-C) is a major contributor to CVD risk. Extensive evidence from clinical studies of statins has demonstrated a linear relationship between LDL-C levels and CVD risk. It has been proposed that lower LDL-C levels than those currently recommended may provide additional clinical benefit to patients. AIM: This review summarises the genetic and clinical evidence on the efficacy and safety of achieving very low LDL-C levels...
November 2016: International Journal of Clinical Practice
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