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https://www.readbyqxmd.com/read/29346544/so-low%C3%A2-so-far-so-good-neurocognitive-impact-of-lowering-ldl-c-levels-with-pcsk9-inhibitors
#1
Baris Gencer, François Mach
No abstract text is available yet for this article.
January 16, 2018: European Heart Journal
https://www.readbyqxmd.com/read/29342010/the-ever-expanding-saga-of-the-proprotein-convertases-and-their-roles-in-body-homeostasis-emphasis-on-novel-proprotein-convertase-subtilisin-kexin-number-9-functions-and-regulation
#2
Nabil G Seidah, Michel Chrétien, Majambu Mbikay
PURPOSE OF REVIEW: The nine members of the proprotein convertase family play major physiological roles during development and in the adult, and their dysregulation leads to various diseases. The primary objective of this article is to review recent findings on the clinical importance of some of these convertases concentrating mostly on PCSK9, the ninth member of the convertase family. This includes the transcriptional and translational regulation of PCSK9, its ability to enhance the degradation of LDL receptor (LDLR), and the implication of PCSK9 in inflammation and sepsis...
January 15, 2018: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/29336946/ldl-cholesterol-how-low-to-go
#3
REVIEW
Chris J Packard
Epidemiology and the results of large-scale outcome trials indicate that the association of LDL with atherosclerotic cardiovascular disease is causal, and continuous not only across levels seen in the general population but also down to sub-physiological values. There is no scientific basis, therefore, to set a target or 'floor' for LDL cholesterol lowering, and this presents a clinical and conceptual dilemma for prescribers, patients, and payers. With the advent of powerful agents such as proprotein convertase/subtilisin kexin type 9 (PCSK9) inhibitors, LDL cholesterol can be lowered profoundly but health economic constraints mandate that this therapeutic approach needs to be selective...
December 28, 2017: Trends in Cardiovascular Medicine
https://www.readbyqxmd.com/read/29335943/-pcsk9-inhibitors-for-which-patients-for-which-indication-what-to-consider
#4
REVIEW
Kristina Busygina, Klaus G Parhofer
No abstract text is available yet for this article.
January 2018: MMW Fortschritte der Medizin
https://www.readbyqxmd.com/read/29332570/proprotein-convertase-subtilisin-kexin-type-9-inhibition-in-cardiovascular-prevention
#5
Ali Ali, Pierluigi Costanzo, Angela Hoye
Elevated levels of Low Density Lipoprotein cholesterol (LDL-C) are directly associated with increased risk for atherosclerotic cardiovascular and cerebrovascular events. Statins have been used to control serum LDL-C and this has translated into reduction in cardiovascular and cerebrovascular events. However, despite high dose statin therapy, LDL-C control may remain inadequate in some patients, particularly those with familial hypercholesterolemia. A new therapeutic approach has emerged in recent years with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors...
January 10, 2018: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/29315397/cost-effectiveness-with-pcsk9-inhibitors-a-matter-of-costs
#6
Heinz Drexel
No abstract text is available yet for this article.
January 1, 2018: European Heart Journal. Cardiovascular Pharmacotherapy
https://www.readbyqxmd.com/read/29306457/cost-effectiveness-of-pcsk9-inhibition-in-addition-to-standard-lipid-lowering-therapy-in-patients-at-high-risk-for-vascular-disease
#7
Manon C Stam-Slob, Yolanda van der Graaf, Anthonius de Boer, Jacoba P Greving, Frank L J Visseren
BACKGROUND: As proprotein convertase subtilisin-kexin type 9 (PCSK9) monoclonal antibodies are entering the market, we assessed the cost-effectiveness of PCSK9 inhibition added to standard lipid-lowering therapy in patient groups at high risk for major adverse cardiovascular events (MACE). METHODS: A lifetime Markov Model was designed to estimate healthcare costs, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs) for PCSK9 inhibition added to standard therapy in patients with Familial Hypercholesterolemia (FH), patients with vascular disease at high MACE recurrence risk, and patients with vascular disease with diabetes mellitus...
February 15, 2018: International Journal of Cardiology
https://www.readbyqxmd.com/read/29305812/proprotein-convertase-subtilisin-kexin-type-9-pcsk9-inhibitors-and-cardiovascular-risk-does-a-further-analysis-of-the-fourier-trial-suggest-changes-in-the-target-of-lipid-lowering-therapy
#8
EDITORIAL
Nazzareno Cervelli, Giuliano Tocci, Claudio Ferri
No abstract text is available yet for this article.
January 5, 2018: High Blood Pressure & Cardiovascular Prevention: the Official Journal of the Italian Society of Hypertension
https://www.readbyqxmd.com/read/29283060/effects-of-high-intensity-statin-therapy-in-the-treatment-of-diabetic-dyslipidemia-in-patients-with-coronary-artery-disease
#9
Marija Vavlukis, Sasko Kedev
BACKGROUND: Diabetic dyslipidemia has specifics that differ from dyslipidemia in patients without diabetes, which contributes to accelerated atherosclerosis equally as dysglycemia. The aim of this study was to deduce the interdependence of diabetic dyslipidemia and cardiovascular diseases (CVD), therapeutic strategies and the risk of diabetes development with statin therapy. METHOD: We conducted a literature review of English articles through PubMed, PubMed Central and Cochrane, on the role of diabetic dyslipidemia in atherosclerosis, the antilipemic treatment with statins, and the role of statin therapy in newly developed diabetes, by using key words: atherosclerosis, diabetes mellitus, diabetic dyslipidemia, CVD, statins, nicotinic acid, fibrates, PCSK9 inhibitors...
December 27, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/29281604/results-of-the-glagov-trial
#10
REVIEW
Steven E Nissen, Stephen J Nicholls
Statins therapy reduces atheroma in proportion to the reduction of low-density lipoprotein cholesterol (LDL-C). Proprotein convertase subtilisin--kexin type 9 (PCSK9) inhibitors are a new class of injectable human monoclonal antibodies shown to lower LDL-C when added to statin therapy. In a randomized, double-blind, placebo-controlled study, 968 patients with symptomatic coronary artery disease were treated with statins alone or combined with the PCSK9 inhibitor, evolocumab, and assessed for change in percent, total volume, and regression of coronary atheroma...
December 2017: Cleveland Clinic Journal of Medicine
https://www.readbyqxmd.com/read/29273581/mortality-differences-associated-with-treatment-responses-in-cantos-and-fourier-insights-and-implications
#11
Paul M Ridker
Similarities and differences in two contemporary post-randomization on-treatment analyses from the FOURIER and CANTOS trials may provide insight into what factors drive reductions in cardiovascular mortality and all-cause mortality among atherosclerosis patients already treated with high intensity statins. In the first paper, the FOURIER investigators elegantly demonstrate that lower is better for low-density lipoprotein cholesterol (LDLC) after adjunctive therapy with the PCSK9 inhibitor evolocumab1 For the FOURIER primary endpoint (a composite of myocardial infarction, stroke, coronary revascularization, unstable angina, or cardiovascular death), there was a highly significant monotonic relationship between sequentially lower achieved LDLC concentrations and lower cardiovascular risk, extending even to those with on-treatment LDLC below 20 mg/dL...
December 22, 2017: Circulation
https://www.readbyqxmd.com/read/29260404/new-treatment-options-for-lipid-lowering-therapy-in-subjects-with-type-2-diabetes
#12
Roberto Scicali, Antonino Di Pino, Viviana Ferrara, Francesca Urbano, Salvatore Piro, Agata Maria Rabuazzo, Francesco Purrello
Dyslipidemias represent a variety of quantitative and/or qualitative lipoprotein abnormalities. According to etiology, we distinguish primary dyslipidemias with strictly genetic background and secondary ones with their origin in other disease or pathological states. Diabetic dyslipidemia is a type of secondary dyslipidemia and plays an important role in determining the cardiovascular risk of subjects with type 2 diabetes. In these patients, insulin resistance is responsible for overproduction and secretion of atherogenic very low density lipoprotein...
December 19, 2017: Acta Diabetologica
https://www.readbyqxmd.com/read/29259136/stepwise-processing-analyses-of-the-single-turnover-pcsk9-protease-reveal-its-substrate-sequence-specificity-and-link-clinical-genotype-to-lipid-phenotype
#13
John S Chorba, Adri M Galvan, Kevan M Shokat
Proprotein convertase subtilisin/kexin type 9 (PCSK9) downregulates the low-density lipoprotein (LDL) receptor (LDL-R), elevating LDL cholesterol (LDL-C) and accelerating atherosclerotic heart disease, making it a promising cardiovascular drug target. To achieve its maximal effect on the LDL-R, PCSK9 requires auto-proteolysis. After cleavage, PCSK9 retains its prodomain in the active site as a self-inhibitor. Unlike other proprotein convertases, however, this retention is permanent, inhibiting any further protease activity for the remainder of its life cycle...
December 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29245109/autosomal-recessive-hypercholesterolemia-in-spain
#14
Rosa María Sánchez-Hernández, Pablo Prieto-Matos, Fernando Civeira, Eduardo Esteve Lafuente, Manuel Frías Vargas, José T Real, Fernando Goñi Goicoechea, Francisco J Fuentes, Miguel Pocovi, Mauro Boronat, Ana María Wägner, Luis Masana
BACKGROUND AND AIMS: Autosomal recessive hypercholesterolemia (ARH) is a very rare disease, caused by mutations in LDL protein receptor adaptor 1 (LDLRAP1). It is characterized by high levels of low-density lipoprotein cholesterol (LDL-C) and increased risk of premature cardiovascular disease. We aimed to characterize ARH in Spain. METHODS: Data were collected from the Dyslipidemia Registry of the Spanish Atherosclerosis Society. A literature search was performed up to June 2017, and all diagnostic genetic studies for familial hypercholesterolemia of Spain were reviewed...
December 6, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/29241886/pcsk9-inhibitors-show-value-for-patients-and-the-us-health-care-system
#15
Wei-Han Cheng, Étienne Gaudette, Dana P Goldman
BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors were approved by the US Food and Drug Administration (FDA) as cholesterol-lowering therapies for patients with familial hypercholesterolemia or atherosclerotic cardiovascular disease. OBJECTIVES: To estimate the long-term health and economic value of PCSK9 inhibitors for Americans (51 years and older). METHODS: We conducted simulations using the Future Elderly Model, an established dynamic microsimulation model to project the lifetime outcomes for the US population aged 51 years and older...
December 2017: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
https://www.readbyqxmd.com/read/29236976/-highest-risk-highest-benefit-strategy-a-pragmatic-cost-effective-approach-to-targeting-use-of-pcsk9-inhibitor-therapies
#16
Lieven Annemans, Chris J Packard, Andrew Briggs, Kausik K Ray
No abstract text is available yet for this article.
December 11, 2017: European Heart Journal
https://www.readbyqxmd.com/read/29231064/pharmacokinetics-pharmacodynamics-and-clinical-efficacy-of-non-statin-treatments-for-hypercholesterolemia
#17
REVIEW
Arrigo F G Cicero, Marilisa Bove, Claudio Borghi
Hypercholesterolemia is the main modifiable risk factor for atherosclerosis progression and cardiovascular disease (CVD) development. Its pharmacological management is usually based on the prescription of statins, that in some cases are not however fully effective to reach the desired Low-Density-Lipoproteins cholesterol (LDL-C) target, or are not tolerated by patients due to side effects. Areas covered: This manuscript summarizes the basic properties of the emerging new classes of lipid-lowering drugs such as ezetimibe, Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) inhibitors, and Microsomal Triglyceride Transfer Protein (MTP) inhibitors, also citing new drugs in development...
January 2018: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/29223954/effect-of-pcsk9-inhibitors-on-clinical-outcomes-in-patients-with-hypercholesterolemia-a-meta-analysis-of-35-randomized-controlled-trials
#18
REVIEW
Aris Karatasakis, Barbara A Danek, Judit Karacsonyi, Bavana V Rangan, Michele K Roesle, Thomas Knickelbine, Michael D Miedema, Houman Khalili, Zahid Ahmad, Shuaib Abdullah, Subhash Banerjee, Emmanouil S Brilakis
BACKGROUND: We sought to examine the efficacy and safety of 2 PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors: alirocumab and evolocumab. METHODS AND RESULTS: We performed a systematic review and meta-analysis of randomized controlled trials comparing treatment with and without PCSK9 inhibitors; 35 randomized controlled trials comprising 45 539 patients (mean follow-up: 85.5 weeks) were included. Mean age was 61.0±2.8 years, and mean baseline low-density lipoprotein cholesterol was 106±22 mg/dL...
December 9, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29219151/familial-hypercholesterolaemia
#19
REVIEW
Joep C Defesche, Samuel S Gidding, Mariko Harada-Shiba, Robert A Hegele, Raul D Santos, Anthony S Wierzbicki
Familial hypercholesterolaemia is a common inherited disorder characterized by abnormally elevated serum levels of low-density lipoprotein (LDL) cholesterol from birth, which in time can lead to cardiovascular disease (CVD). Most cases are caused by autosomal dominant mutations in LDLR, which encodes the LDL receptor, although mutations in other genes coding for proteins involved in cholesterol metabolism or LDLR function and processing, such as APOB and PCSK9, can also be causative, although less frequently...
December 7, 2017: Nature Reviews. Disease Primers
https://www.readbyqxmd.com/read/29210646/pcsk9-and-hypercholesterolemia-therapeutical-approach
#20
Milan Obradovic, Bozidarka Zaric, Emina Sudar-Milovanovic, Branislava Ilincic, Milan Perovic, Edita Stokic, Esma Isenovic
Despite the intensive research and progress in modern pharmacotherapy, hypercholesterolemia and related cardiovascular complications remain one of the leading causes of mortality and disability in the modern world. A significant contribution to the treatment of hypercholesterolemia was made by the discovery of proprotein convertase subtilisin/kexin type 9 (PCSK9). This enzyme is responsible for the degradation of the low-density lipoprotein (LDL) receptor (LDLR) found at the surface of the plasma membrane in the liver and directly associated with serum LDL level...
December 4, 2017: Current Drug Targets
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