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https://www.readbyqxmd.com/read/28096572/current-and-emerging-treatments-for-hypercholesterolemia-a-focus-on-statins-and-proprotein-convertase-subtilisin-kexin-type-9-inhibitors-for-perioperative-clinicians
#1
REVIEW
Terrence L Trentman, Steven G Avey, Harish Ramakrishna
Statins are a mainstay of hyperlipidemia treatment. These drugs inhibit the enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase and have beneficial effects on atherosclerosis including plaque stabilization, reduction of platelet activation, and reduction of plaque proliferation and inflammation. Statins also have a benefit beyond atherosclerotic plaque, including anticoagulation, vasodilatation, antioxidant effects, and reduction of mediators of inflammation. In the perioperative period, statins appear to contribute to improved outcomes via these mechanisms...
October 2016: Journal of Anaesthesiology, Clinical Pharmacology
https://www.readbyqxmd.com/read/28081164/economic-evaluation-of-pcsk9-inhibitors-in-reducing-cardiovascular-risk-from-health-system-and-private-payer-perspectives
#2
Alejandro Arrieta, Timothy F Page, Emir Veledar, Khurram Nasir
The introduction of Proprotein covertase subtilisin/kexin type 9 (PCSK9) inhibitors has been heralded as a major advancement in reducing low-density lipoprotein cholesterol levels by nearly 50%. However, concerns have been raised on the added value to the health care system in terms of their costs and benefits. We assess the cost-effectiveness of PCSK9 inhibitors based on a decision-analytic model with existing clinical evidence. The model compares a lipid-lowering therapy based on statin plus PCSK9 inhibitor treatment with statin treatment only (standard therapy)...
2017: PloS One
https://www.readbyqxmd.com/read/28073851/increased-risk-of-adverse-neurocognitive-outcomes-with-proprotein-convertase-subtilisin-kexin-type-9-inhibitors
#3
Abdur Rahman Khan, Chirag Bavishi, Haris Riaz, Talha A Farid, Sobia Khan, Michel Atlas, Glenn Hirsch, Sohail Ikram, Roberto Bolli
BACKGROUND: There is encouraging evidence of the efficacy of proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors; however, their long-term safety remains unclear. We performed a meta-analysis of studies to evaluate the long-term safety of PCSK9 inhibitors. METHODS AND RESULTS: Our search strategy yielded 11 studies (9 smaller early-phase and 2 larger outcome trials). The outcomes assessed were cumulative serious adverse events, musculoskeletal adverse events, neurocognitive adverse events, and stroke...
January 2017: Circulation. Cardiovascular Quality and Outcomes
https://www.readbyqxmd.com/read/28038950/pcsk9-inhibitors-in-the-current-management-of-atherosclerosis
#4
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/28028691/sirolimus-therapy-is-associated-with-elevation-in-circulating-pcsk9-levels-in-cardiac-transplant-patients
#5
Vinaya Simha, Sisi Qin, Pankaj Shah, Byron H Smith, Walter K Kremers, Sudhir Kushwaha, Liewei Wang, Naveen L Pereira
Sirolimus used in transplantation is often associated with hypercholesterolemia. We measured serum lipid and PCSK9 levels in 51 heart transplant recipients who had their immunosuppressive therapy switched from calcineurin inhibitors to sirolimus. The switch resulted in a 23% increase in LDL cholesterol, and 46% increase in triglycerides and PCSK9 levels increased from 316 ± 105 ng/mL to 343 ± 107 ng/mL (p = 0.04), however the change in PCSK9 levels did not correlate with an increase in lipid levels (p = 0...
December 27, 2016: Journal of Cardiovascular Translational Research
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
#6
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/27986868/proprotein-convertase-subtilisin-kexin-type-9-pcsk9-single-domain-antibodies-are-potent-inhibitors-of-low-density-lipoprotein-receptor-degradation
#7
Elodie Weider, Delia Susan-Resiga, Rachid Essalmani, Josée Hamelin, Marie-Claude Asselin, Surendra Nimesh, Yahya Ashraf, Keith L Wycoff, Jianbing Zhang, Annik Prat, Nabil G Seidah
No abstract text is available yet for this article.
December 16, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27986651/effects-of-pcsk9-inhibition-with-alirocumab-on-lipoprotein-metabolism-in-healthy-humans
#8
Gissette Reyes-Soffer, Marianna Pavlyha, Colleen Ngai, Tiffany Thomas, Stephen Holleran, Rajasekhar Ramakrishnan, Wahida Karmally, Renu Nandakumar, Nelson Fontanez, Joseph C Obunike, Santica M Marcovina, Alice H Lichtenstein, Nirupa R Matthan, James Matta, Magali Maroccia, Frederic Becue, Franck Poitiers, Brian Swanson, Lisa Cowan, William J Sasiela, Howard K Surks, Henry N Ginsberg
BACKGROUND: -Alirocumab, a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9), lowers plasma low density lipoprotein cholesterol (LDL-C) and apolipoprotein B100 (apoB). Although studies in mice and cells have identified increased hepatic LDL receptors as the basis for LDL lowering by PCSK9 inhibitors, there have been no human studies characterizing the effects of PCSK9 inhibitors on lipoprotein metabolism. In particular, it is not known if inhibition of PCSK9 has any effects on very low density lipoprotein (VLDL) or intermediate density lipoprotein (IDL) metabolism...
December 16, 2016: Circulation
https://www.readbyqxmd.com/read/27973021/pcsk9-inhibitors-may-improve-cardiovascular-outcomes-can-we-afford-them
#9
R Arbel, A Hammerman, N Triki, D Greenberg
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/27972117/pcsk9-inhibitors-identification-of-eligible-patients-from-regional-administrative-healthcare-databases
#10
M Andretta, A M Menti, M Polini, Esposti L Degli, C Bilato, A Zambon, G Scroccaro
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/27972028/the-potential-budget-impact-of-pcsk9-inhibitors-in-ireland
#11
H O'Donnell, L McCullagh, M Barry
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/27971806/drivers-in-hta-decision-making-for-cholesterol-lowering-pcsk9-inhibitors
#12
J Kreeftmeijer, R Dekkers, A van Engen
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/27967828/homozygous-familial-hypercholesterolaemia-update-on-management
#13
Michael France
Homozygous familial hypercholesterolaemia (HoFH) is an inherited disease causing an approximately fourfold increase in blood low-density lipoprotein cholesterol (LDLC) from birth compared with the age-matched normal population owing to reduced low-density lipoprotein receptor (LDLR) activity. Such elevated cholesterol is associated with accelerated atheromatous disease, particularly of the aortic root and coronary arteries. However, HoFH is clinically heterogeneous, reflecting residual low-density lipoprotein receptor (LDLR) activity...
November 2016: Paediatrics and International Child Health
https://www.readbyqxmd.com/read/27967260/pcsk9-inhibitors-in-sepsis-a-new-potential-indication
#14
Amir Abbas Momtazi, Maciej Banach, Amirhossein Sahebkar
No abstract text is available yet for this article.
December 21, 2016: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/27959767/variation-in-pcsk9-and-hmgcr-and-risk-of-cardiovascular-disease-and-diabetes
#15
Brian A Ference, Jennifer G Robinson, Robert D Brook, Alberico L Catapano, M John Chapman, David R Neff, Szilard Voros, Robert P Giugliano, George Davey Smith, Sergio Fazio, Marc S Sabatine
Background Pharmacologic inhibitors of proprotein convertase subtilisin-kexin type 9 (PCSK9) are being evaluated in clinical trials for the treatment of cardiovascular disease. The effect of lowering low-density lipoprotein (LDL) cholesterol levels by inhibiting PCSK9 on the risk of cardiovascular events or diabetes is unknown. Methods We used genetic scores consisting of independently inherited variants in the genes encoding PCSK9 and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR; the target of statins) as instruments to randomly assign 112,772 participants from 14 studies, with 14,120 cardiovascular events and 10,635 cases of diabetes, to groups according to the number of LDL cholesterol-lowering alleles that they had inherited...
1, 2016: New England Journal of Medicine
https://www.readbyqxmd.com/read/27959715/a-highly-durable-rnai-therapeutic-inhibitor-of-pcsk9
#16
Kevin Fitzgerald, Suellen White, Anna Borodovsky, Brian R Bettencourt, Andrew Strahs, Valerie Clausen, Peter Wijngaard, Jay D Horton, Jorg Taubel, Ashley Brooks, Chamikara Fernando, Robert S Kauffman, David Kallend, Akshay Vaishnaw, Amy Simon
Background Inclisiran (ALN-PCSsc) is a long-acting RNA interference (RNAi) therapeutic agent that inhibits the synthesis of proprotein convertase subtilisin-kexin type 9 (PCSK9), a target for the lowering of low-density lipoprotein (LDL) cholesterol. Methods In this phase 1 trial, we randomly assigned healthy volunteers with an LDL cholesterol level of at least 100 mg per deciliter in a 3:1 ratio to receive a subcutaneous injection of inclisiran or placebo in either a single-ascending-dose phase (at a dose of 25, 100, 300, 500, or 800 mg) or a multiple-dose phase (125 mg weekly for four doses, 250 mg every other week for two doses, or 300 or 500 mg monthly for two doses, with or without concurrent statin therapy); each dose cohort included four to eight participants...
January 5, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/27927063/inflammation-and-beyond-new-directions-and-emerging-drugs-for-treating-atherosclerosis
#17
Marie-Jeanne Bertrand, Jean-Claude Tardif
Cardiovascular (CV) atherosclerotic disease remains the leading cause of morbidity and mortality worldwide, despite the advances in contemporary therapies. Inflammation is an important process in atherosclerosis, leading to plaque rupture and acute coronary syndrome. Although statin therapy has substantially reduced CV events in primary and secondary prevention, many treated patients will have recurrent adverse CV events despite the standard of care. Thus, drug development aiming to target inflammatory pathways seems a promising avenue for novel therapies in atherosclerosis...
December 22, 2016: Expert Opinion on Emerging Drugs
https://www.readbyqxmd.com/read/27923854/lipoprotein-a-another-emergent-target-for-pcsk9-inhibitors
#18
(no author information available yet)
No abstract text is available yet for this article.
October 14, 2016: European Heart Journal
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
#19
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/27919350/identification-and-characterization-of-severe-familial-hypercholesterolemia-in-patients-presenting-for-cardiac-catheterization
#20
Barak Zafrir, Chen Shapira, Gil Lavie, David A Halon, Moshe Y Flugelman
BACKGROUND: Patients with severe familial hypercholesterolemia (FH) are often unrecognized despite typical presentation. The introduction of PCSK9 inhibitors opens new therapeutic options and emphasizes the need for identification of severe FH patients. OBJECTIVES: The objective was identification, characterization, and management of severe FH patients by screening of cardiac catheterization (CC) database. METHODS: Retrospective analysis of CC database from 2002 to mid-2015 was performed for low-density lipoprotein cholesterol (LDL-C) ≥130 mg/dL (n = 2383)...
November 2016: Journal of Clinical Lipidology
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