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https://www.readbyqxmd.com/read/29777433/are-pcsk9-inhibitors-cost-effective
#1
Max J Korman, Kjetil Retterstøl, Ivar Sønbø Kristiansen, Torbjørn Wisløff
The objective of this study was to review available health economic evaluations of PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors. These drugs reduce low-density lipid cholesterol levels and cardiovascular risk, but their cost effectiveness has been questioned. We searched Medline and Embase for economic evaluations in any language at any time. Studies were included if they analysed any PCSK9 inhibitor compared with either statin alone or in combination with ezetimibe or any other therapy considered standard prior to the introduction of PCSK9 inhibitors...
May 18, 2018: PharmacoEconomics
https://www.readbyqxmd.com/read/29773421/r46l-polymorphism-in-the-pcsk9-gene-relationship-to-lipid-levels-subclinical-vascular-disease-and-erectile-dysfunction
#2
Jose M Mostaza, Carlos Lahoz, Miguel A Salinero-Fort, Olaya de Dios, Elisa Castillo, Teresa González-Alegre, Francisca García-Iglesias, Eva Estirado, Fernando Laguna, Concesa Sabín, Silvia López, Victor Cornejo, Carmen de Burgos, Vanesa Sanchez, Carmen Garcés
BACKGROUND: The R46L variant of the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene has been related to lipid levels and cardiovascular disease. OBJECTIVE: To evaluate the influence of this polymorphism on subclinical vascular disease and erectile dysfunction (ED). METHODS: We analyzed the association of the PCSK9 rs11591147 single-nucleotide polymorphism with lipid levels, intima-media thickness (IMT), and the ankle-brachial index, in 1188 adults free of cardiovascular disease, randomly selected from the population...
April 21, 2018: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/29770231/cardiovascular-outcomes-of-pcsk9-inhibitors-with-special-emphasis-on-its-effect-beyond-ldl-cholesterol-lowering
#3
REVIEW
Dhrubajyoti Bandyopadhyay, Kumar Ashish, Adrija Hajra, Arshna Qureshi, Raktim K Ghosh
PCSK9 inhibitors, monoclonal antibodies, are novel antihypercholesterolemic drugs. FDA first approved them in July 2015. PCSK9 protein (692-amino acids) was discovered in 2003. It plays a major role in LDL receptor degradation and is a prominent modulator in low-density lipoprotein cholesterol (LDL-C) metabolism. PCSK9 inhibitors are monoclonal antibodies that target PCSK9 protein in liver and inhibiting this protein leads to drastically lowering harmful LDL-C level in the bloodstream. Despite widespread use of the statin, not all the high-risk patients were able to achieve targeted level of LDL-C...
2018: Journal of Lipids
https://www.readbyqxmd.com/read/29768954/comparison-of-ldl-c-reduction-using-different-evolocumab-doses-and-intervals-biological-insights-and-treatment-implications
#4
Scott M Wasserman, Marc S Sabatine, Michael J Koren, Robert P Giugliano, Jason C Legg, Maurice G Emery, Sameer Doshi, Thomas Liu, Ransi Somaratne, John P Gibbs
BACKGROUND: The proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor evolocumab reduces low-density lipoprotein cholesterol (LDL-C) and the risk of cardiovascular events. OBJECTIVES: To compare LDL-C reduction using evolocumab 140 mg once every 2 weeks (Q2W) or 420 mg monthly (QM) versus lower doses (70 mg Q2W or 280 mg QM) or placebo. METHODS: Patients received evolocumab 70 or 140 mg Q2W, 280 or 420 mg QM, or placebo Q2W or QM in two 12-week phase 2 studies: one with and one without statins...
January 1, 2018: Journal of Cardiovascular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29758414/role-of-pcsk9-in-lipid-metabolism-and-atherosclerosis
#5
REVIEW
Xiao-Long Lin, Le-Le Xiao, Zhi-Han Tang, Zhi-Sheng Jiang, Mi-Hua Liu
Elevated plasma low-density lipoprotein cholesterol (LDL-C) is an important risk factor for cardiovascular diseases. Statins are the most widely used therapy for patients with hyperlipidemia. However, a significant residual cardiovascular risk remains in some patients even after maximally tolerated statin therapy. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a new pharmacologically therapeutic target for decreasing LDL-C. PCSK9 reduces LDL intake from circulation by enhancing LDLR degradation and preventing LDLR recirculation to the cell surface...
May 11, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29754909/serum-pcsk9-levels-predict-the-occurrence-of-acute-coronary-syndromes-in-patients-with-severe-carotid-artery-stenosis
#6
Luca Liberale, Federico Carbone, Maria Bertolotto, Aldo Bonaventura, Alessandra Vecchié, François Mach, Fabienne Burger, Aldo Pende, Giovanni Spinella, Bianca Pane, Giovanni G Camici, Domenico Palombo, Franco Dallegri, Fabrizio Montecucco
BACKGROUND: The pharmacological inhibition of Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) has shown to dramatically impact on low-density lipoprotein-cholesterol (LDL-C) levels and associated cardiovascular (CV) diseases. However, the potential use of PCSK9 serum levels as a CV risk biomarker remains to be clarified. METHODS: 189 patients with severe carotid artery atherosclerosis undergoing carotid endarterectomy (CEA) and whose clinical records and serum sample aliquots for PCSK9 level measurement were available both directly before CEA and at 24-month follow-up were included in the present pilot study...
July 15, 2018: International Journal of Cardiology
https://www.readbyqxmd.com/read/29748367/pcsk9-from-basic-science-discoveries-to-clinical-trials
#7
REVIEW
Michael D Shapiro, Hagai Tavori, Sergio Fazio
Unknown 15 years ago, PCSK9 (proprotein convertase subtilisin/kexin type 9) is now common parlance among scientists and clinicians interested in prevention and treatment of atherosclerotic cardiovascular disease. What makes this story so special is not its recent discovery nor the fact that it uncovered previously unknown biology but rather that these important scientific insights have been translated into an effective medical therapy in record time. Indeed, the translation of this discovery to novel therapeutic serves as one of the best examples of how genetic insights can be leveraged into intelligent target drug discovery...
May 11, 2018: Circulation Research
https://www.readbyqxmd.com/read/29748356/variation-in-lipid-lowering-therapy-use-in-patients-with-low-density-lipoprotein-cholesterol-%C3%A2-190-mg-dl-insights-from-the-national-cardiovascular-data-registry-practice-innovation-and-clinical-excellence-registry
#8
Salim S Virani, Kevin F Kennedy, Julia M Akeroyd, Pamela B Morris, Vera A Bittner, Frederick A Masoudi, Neil J Stone, Laura A Petersen, Christie M Ballantyne
BACKGROUND: Patients with low-density lipoprotein cholesterol (LDL-C) ≥190 mg/dL are at high risk of atherosclerotic cardiovascular disease events. Treatment guidelines recommend intensive treatment in these patients. Variation in the use of lipid-lowering therapies (LLTs) in these patients in a national sample of cardiology practices is not known. METHODS AND RESULTS: Using data from the American College of Cardiology National Cardiovascular Data Registry-Practice Innovation and Clinical Excellence registry, we assessed the proportion of patients with LDL-C ≥190 mg/dL (n=49 447) receiving statin, high-intensity statin, LLT associated with ≥50% LDL-C lowering, ezetimibe, or a PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor between January 2013 and December 2016...
May 2018: Circulation. Cardiovascular Quality and Outcomes
https://www.readbyqxmd.com/read/29748320/genetic-regulation-of-pcsk9-proprotein-convertase-subtilisin-kexin-type-9-plasma-levels-another-piece-of-the-puzzle
#9
EDITORIAL
Martine Paquette, Alexis Baass
No abstract text is available yet for this article.
May 2018: Circulation. Genomic and precision medicine
https://www.readbyqxmd.com/read/29748315/genetic-regulation-of-pcsk9-proprotein-convertase-subtilisin-kexin-type-9-plasma-levels-and-its-impact-on-atherosclerotic-vascular-disease-phenotypes
#10
Janne Pott, Valentin Schlegel, Andrej Teren, Katrin Horn, Holger Kirsten, Christina Bluecher, Juergen Kratzsch, Markus Loeffler, Joachim Thiery, Ralph Burkhardt, Markus Scholz
BACKGROUND: Inhibition of PCSK9 (proprotein convertase subtilisin/kexin type 9) is a novel strategy to treat hypercholesterolemia and reduce cardiovascular events. However, the potential role of circulating plasma PCSK9 concentrations as a diagnostic and predictive biomarker remains uncertain as of now. Here, we aimed to identify genetic variants associated with plasma PCSK9 and investigate possible causal effects on atherosclerotic vascular disease phenotypes. METHODS: We performed the first genome-wide association study of plasma PCSK9 levels in a cohort of suspected and confirmed coronary artery disease (LIFE-Heart; n=3290)...
May 2018: Circulation. Genomic and precision medicine
https://www.readbyqxmd.com/read/29747383/current-role-of-lipoprotein-apheresis-in-the-treatment-of-high-risk-patients
#11
REVIEW
Ulrich Julius
Lipoprotein apheresis (LA) is a therapeutic approach to save the lives of patients who are at an extremely high risk of developing cardiovascular events (CVE), especially after all other therapeutic options were not tolerated, or appeared not to be effective enough. Homozygous familial hypercholesterolemia represents a clear indication to start LA therapy. Another recognized indication is a severe hypercholesterolemia, which induced CVE, often in association with other risk factors. In the last years, an expressive elevation of lipoprotein(a) (Lp(a)) emerged as an indication for LA...
May 9, 2018: Journal of Cardiovascular Development and Disease
https://www.readbyqxmd.com/read/29742924/inhibition-of-aortic-calcification-by-policosanol-in-dyslipidemic-rabbits-is-enhanced-by-pentoxifylline-potential-role-of-pcsk9
#12
Mohamed M Elseweidy, Hoda E Mohamed, Rania A Elrashidy, Hebatallah H Atteia, Gehad M Elnagar
Policosanol (POL) is a hypocholesterolemic drug of natural origin and has been shown to reduce circulating levels of proprotein convertase subtilisin/kexin type 9 (PCSK9) in healthy participants. Recently, we have reported that POL can attenuate aortic calcification in diabetic dyslipidemic rats; however, the underlying mechanism is not fully elucidated. We aimed to investigate the effect of POL on aortic calcification and whether PCSK9 has a contributory role and also to examine whether the combination of POL with pentoxifylline (PTX) as anti-tumor necrosis factor α would offer additional benefits...
January 1, 2018: Journal of Cardiovascular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29740798/new-insight-on-a-combination-of-policosanol-and-10-dehydrogingerdione-phytochemicals-as-inhibitors-for-platelet-activation-biomarkers-and-atherogenicity-risk-in-dyslipidemic-rabbits-role-of-cetp-and-pcsk9-inhibition
#13
Mohamed Mahmoud Elseweidy, Rawia Sarhan Amin, Hebatallah Husseini Atteia, Reham Raafat El-Zeiky, Naif A Al-Gabri
Platelet markers [soluble p selectin (sP-selectin) and soluble CD40 ligand (sCD40L)] are associated with platelet activation and cardiovascular risk. Both policosanol and 10-dehydrogingerdione are natural products with proven CETP inhibitory and antiatherogenic effects. Present work aimed mainly to investigate the levels of platelet activation biomarkers in the serum of dyslipidemic rabbits and the potential of these phytochemicals either alone or in a combination form to protect against atherogenicity. Additionally, this work clarified their effect on PCSK9, a key player in atherosclerosis progression...
May 9, 2018: Applied Biochemistry and Biotechnology
https://www.readbyqxmd.com/read/29738370/biologics-and-cardiovascular-disease
#14
John S Van Taunay, M Teresa Albelda, Juan Carlos Frias, Michael J Lipinski
The advent of biologic therapy has enhanced our ability to augment disease in an increasingly targeted manner. The use of biologics in cardiovascular disease (CVD) has steadily increased over the past several decades. Much of the early data on biologics and CVD were derived from their use in rheumatologic populations. Atherosclerosis, myocardial infarction, and heart failure have been closely linked to the inflammatory response. Accordingly, cytokines such as tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 have been targeted...
May 3, 2018: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/29737886/role-of-proprotein-convertase-subtilisin-kexin-type-9-inhibitors-in-patients-with-coronary-artery-disease-undergoing-percutaneous-coronary-intervention
#15
Eliano P Navarese, Michalina Kołodziejczak, Aniela Petrescu, Bernhard Wernly, Michael Lichtenauer, Alexander Lauten, Antonino Buffon, Wojciech Wanha, Vincenzo Pestrichella, Gennaro Sardella, Gaetano Contegiacomo, Udaya Tantry, Kevin Bliden, Jacek Kubica, Paul A Gurbel
Although novel therapies have improved outcomes in PCI patients, a sizeable number of patients still remain at high cardiovascular risk for recurrent event. There is therefore an unmet need for novel therapies that can improve clinical outcomes, with an associated satisfactory safety profile. Proprotein convertase subtilisin/kexin type 9 (PCSK9) enzyme is a novel lipid-lowering target with a potential to impact high-cardiovascular risk populations including patients with coronary artery disease (CAD), undergoing the percutaneous coronary intervention (PCI)...
May 8, 2018: Expert Review of Cardiovascular Therapy
https://www.readbyqxmd.com/read/29737499/vaccines-targeting-pcsk9-a-promising-alternative-to-passive-immunization-with-monoclonal-antibodies-in-the-management-of-hyperlipidaemia
#16
Stefan Weisshaar, Markus Zeitlinger
Hypercholesterolaemia is frequently observed in patients with cardiovascular diseases (CVD) and is associated with increased mortality. Statin treatment has been the standard of care for reducing low-density lipoprotein cholesterol (LDL-C) to improve cardiovascular outcomes. However, statins have limited effects in some patients and may be discontinued due to adverse effects resulting in LDL-C above target levels. The proprotein convertase subtilisin kexin type 9 (PCSK9) is a pivotal regulator in the LDL-C metabolism by degrading the LDL-C receptor on hepatocytes...
May 8, 2018: Drugs
https://www.readbyqxmd.com/read/29737015/therapeutic-agents-targeting-cardiometabolic-risk-for-preventing-and-treating-atherosclerotic-cardiovascular-diseases
#17
Benoit J Arsenault, Nicolas Perrot, Rishi Puri
Targeting atherogenic lipoprotein levels with statins remains the current cornerstone of atherosclerotic cardiovascular disease (ACVD) management. In patients at high ACVD risk who cannot achieve the desired low-density lipoprotein (LDL) cholesterol target, the addition of compounds such as ezetimibe and proprotein subtilisin/kexin type-9 (PCSK9) inhibitors incrementally lowers cardiovascular risk. New glucose-lowering drugs such as glucacon-like peptide-1 receptor (GLP1R) agonists and sodium-glucose co-transporter-2 (SGLT2) inhibitors were also shown to improve cardiometabolic risk factors and provide cardiovascular benefits in patients with type 2 diabetes...
May 8, 2018: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29735484/effect-of-an-sirna-therapeutic-targeting-pcsk9-on-atherogenic-lipoproteins-pre-specified-secondary-end-points-in-orion-1
#18
Kausik K Ray, Robert M Stoekenbroek, David Kallend, Lawrence A Leiter, Ulf Landmesser, R Scott Wright, Peter Wijngaard, John J Kastelein
Background -The ORION-1 trial demonstrated that inclisiran, a small interfering RNA (siRNA) therapeutic that targets PCSK9 mRNA within hepatocytes, produces significant LDL-C reduction. The effects of inclisiran on other lipids are less well described. Methods -ORION-1 was a phase 2 trial assessing 6 different inclisiran dosing regimens vs placebo. Participants with elevated LDL-C despite receiving maximally tolerated statin therapy received a single- (200, 300 or 500mg) or two-dose starting regimen (100, 200 or 300mg on days 1 and 90) of inclisiran or placebo...
May 7, 2018: Circulation
https://www.readbyqxmd.com/read/29731350/the-cost-effectiveness-of-pcsk9-inhibitors-the-australian-healthcare-perspective
#19
Radya Kumar, Andrew Tonkin, Danny Liew, Ella Zomer
BACKGROUND: For patients in whom statins are not tolerated or effective as monotherapy, proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) represent a new class of lipid lowering therapies that may reduce low-density lipoprotein cholesterol (LDL-C) levels by up to 50% and lower cardiovascular events. While an important treatment option, the cost-effectiveness of PCSK9i in Australia remains unknown. This study aimed to determine the cost-effectiveness of PCSK9i compared to placebo in the prevention of atherosclerotic cardiovascular disease (CVD)...
April 26, 2018: International Journal of Cardiology
https://www.readbyqxmd.com/read/29728531/stepwise-processing-analyses-of-the-single-turnover-pcsk9-protease-reveal-its-substrate-sequence-specificity-and-link-clinical-genotype-to-lipid-phenotype
#20
John S Chorba, Adri M Galvan, Kevan M Shokat
No abstract text is available yet for this article.
May 4, 2018: Journal of Biological Chemistry
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