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https://www.readbyqxmd.com/read/29148854/comparative-effectiveness-of-lipid-lowering-treatments-to-reduce-cardiovascular-disease
#1
Dong-Churl Suh, Scott K Griggs, Emmett R Henderson, Seung-Mi Lee, Taehwan Park
With the advent of a new drug class - the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, patients have another treatment option for lowering their high levels of low-density lipoprotein cholesterol (LDL-C) in recent years. The objective of this study was to systematically review the cost-effectiveness of lipid-lowering agents such as statins, ezetimibe, and PCSK9 inhibitors. Areas covered: Based on PubMed, Embase, and Cochrane Database of Systematic Reviews, we identified a total of 29 relevant articles...
November 17, 2017: Expert Review of Pharmacoeconomics & Outcomes Research
https://www.readbyqxmd.com/read/29133605/low-density-lipoprotein-cholesterol-lowering-with-evolocumab-and-outcomes-in-patients-with-peripheral-artery-disease-insights-from-the-fourier-trial-further-cardiovascular-outcomes-research-with-pcsk9-inhibition-in-subjects-with-elevated-risk
#2
Marc P Bonaca, Patrice Nault, Robert P Giugliano, Anthony C Keech, Armando Lira Pineda, Estella Kanevsky, Julia Kuder, Sabina A Murphy, J Wouter Jukema, Basil S Lewis, Lale Tokgozoglu, Ransi Somaratne, Peter S Sever, Terje R Pedersen, Marc S Sabatine
BACKGROUND : The PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor evolocumab reduced low-density lipoprotein cholesterol and cardiovascular events in the FOURIER trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk). We investigated the efficacy and safety of evolocumab in patients with peripheral artery disease (PAD) as well as the effect on major adverse limb events. METHODS : FOURIER was a randomized trial of evolocumab versus placebo in 27 564 patients with atherosclerotic disease on statin therapy followed for a median of 2...
November 13, 2017: Circulation
https://www.readbyqxmd.com/read/29122809/eligibility-for-pcsk9-inhibitors-according-to-american-college-of-cardiology-acc-and-european-society-of-cardiology-european-atherosclerosis-society-esc-eas-guidelines-after-acute-coronary-syndromes
#3
Baris Gencer, Konstantinos C Koskinas, Lorenz Räber, Alexios Karagiannis, David Nanchen, Reto Auer, David Carballo, Sebastian Carballo, Roland Klingenberg, Dik Heg, Christian M Matter, Thomas F Lüscher, Nicolas Rodondi, François Mach, Stephan Windecker
BACKGROUND: The American College of Cardiology (ACC) and European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) have recently published recommendations for the use of proprotein convertase subtilisin/kexin-9 (PCSK9) inhibitors in situations of very high risk. We aim to assess in the real world the suitability of PCSK9 inhibitors for acute coronary syndromes. METHODS AND RESULTS: We analyzed a prospective Swiss cohort of 2023 patients hospitalized for acute coronary syndromes between 2009 and 2014 with available data for low-density lipoprotein cholesterol and lipid-lowering therapy at 1 year...
November 9, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29121222/neurological-effects-of-proprotein-convertase-subtilisin-kexin-type-9-inhibitors-direct-comparisons
#4
Navkaranbir S Bajaj, Nirav Patel, Rajat Kalra, Amier Ahmad, Anand Venkatraman, Garima Arora, Pankaj Arora
Aims: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors considerably alter the lipid profile. We sought to examine rates of ischemic stroke, and neurocognitive deficits in patients treated with and without PCSK9 inhibitors. Methods and Results: Randomized controlled trials (RCTs) reporting rates of ischemic stroke, and neurocognitive deficits in patients using PCSK9 inhibitors were identified. Standard meta-analysis techniques were used to compare these outcomes among patients treated with and without PCSK9 inhibitors, and the two U...
October 6, 2017: European Heart Journal. Quality of Care & Clinical Outcomes
https://www.readbyqxmd.com/read/29105679/-a-practical-tool-for-easier-compilation-of-aifa-italian-medicines-agency-web-based-registry-for-pcsk9-inhibitor-prescription
#5
Claudio Bilato, Maurizio Anselmi, Roberto Cemin, Nadia Citroni, Loris Roncon, Alberto Zambon, Sabina Zambon, Maria Grazia Zenti
No abstract text is available yet for this article.
November 2017: Giornale Italiano di Cardiologia
https://www.readbyqxmd.com/read/29103916/effect-of-atorvastatin-cholesterol-ester-transfer-protein-inhibition-and-diabetes-mellitus-on-circulating-proprotein-subtilisin-kexin-type-9-and-lipoprotein-a-levels-in-patients-at-high-cardiovascular-risk
#6
Benoit J Arsenault, Francine Petrides, Fatiha Tabet, Weihang Bao, G Kees Hovingh, S Matthijs Boekholdt, Stéphane Ramin-Mangata, Olivier Meilhac, David DeMicco, Kerry-Anne Rye, David D Waters, John J P Kastelein, Philip Barter, Gilles Lambert
BACKGROUND: Proprotein subtilisin kexin type 9 (PCSK9) and lipoprotein (a) [Lp(a)] levels are causative risk factors for coronary heart disease. OBJECTIVES: The objective of the study was to determine the impact of lipid-lowering treatments on circulating PCSK9 and Lp(a). METHODS: We measured PCSK9 and Lp(a) levels in plasma samples from Investigation of Lipid Level Management to Understand its Impact in Atherosclerotic Events trial patients with coronary heart disease and/or type II diabetes (T2D) mellitus...
October 12, 2017: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/29096860/current-insights-into-the-german-lipoprotein-apheresis-standard-pcsk9-inhibitors-lipoprotein-apheresis-or-both
#7
V J J Schettler, J Ringel, S Jacob, U Julius, R Klingel, F Heigl, E Roeseler, P Grützmacher
According to current European guidelines, lipid lowering therapy for progressive cardiovascular disease including cardiovascular events has to be focused on a target level for LDL-C. In contrast for Lp(a) a threshold has to be defined with respect to the method of measurement. However, due to new lipid lowering drug developments like PCSK9-inhibitors (PCSK-9-I) a therapeutic algorithm for patients with severe hypercholesterolemia or isolated Lipoprotein(a)-hyperlipoproteinemia with progressive cardiovascular disease may be necessary to manage the use of PCSK9-I, lipoprotein apheresis (LA) or both...
November 2017: Atherosclerosis. Supplements
https://www.readbyqxmd.com/read/29096859/lipoprotein-a-apheresis-in-the-light-of-new-drug-developments
#8
Anja Vogt
Elevated levels of lipoprotein(a) (Lp(a)) contribute to the risk of early and severe cardiovascular disease (CVD). Recently <50 mg/dl was recommended as the desirable level for clinical use and decision making. All established medical therapies to lower cholesterol levels have no impact on lowering Lp(a) except niacin which is all too often poorly tolerated and not obtainable everywhere. Lipoprotein apheresis is an extracorporeal treatment to lower levels of Lp(a) significantly by > 60%. In some countries it is recommended in very high risk patients with early or progressive CVD...
November 2017: Atherosclerosis. Supplements
https://www.readbyqxmd.com/read/29096858/management-of-patients-with-statin-intolerance
#9
Sabine Fischer, Ulrich Julius
In recent years statins have become an established option in lipid-lowering pharmacotherapy despite the fact that statin intolerance is fairly common. When muscle pains and/or an elevation of the creatine kinase appear, the dose must be lowered in patients with slight symptoms or stopped altogether if the symptoms are more severe. When the symptoms are alleviated and creatine kinase is normalized, re-exposition can be considered. If symptoms recur, treatment with another statin should be attempted - in these cases pravastatin or fluvastatin are recommended, although they are less effective in reducing LDL cholesterol...
November 2017: Atherosclerosis. Supplements
https://www.readbyqxmd.com/read/29096851/how-effectively-will-pcsk9-inhibitors-allow-retrieval-of-freedom-from-apheresis-in-cardiovascular-high-risk-patients-estimates-form-a-large-single-center
#10
Bernd Hohenstein, Sergey Tselmin, Stefan R Bornstein, Ulrich Julius
Lipoprotein apheresis (LA) has been the last-resort therapeutic option in patients suffering from limited pharmaceutical options to lower highly elevated low density lipoprotein cholesterol (LDL-C) levels. Facing the introduction of the proprotein convertase subtilisin/kexine type 9 (PCSK-9) inhibitors, it has been speculated that they might replace LA to a large extend. Given an efficacy of approx. 55-65% to lower LDL-C it is important to analyze whether this might be realistic i) for potential candidates in apheresis sites and ii) for the future structures of the sites themselves...
November 2017: Atherosclerosis. Supplements
https://www.readbyqxmd.com/read/29096824/history-of-lipidology-and-lipoprotein-apheresis
#11
Ulrich Julius
This review tells the story of atherosclerosis research in the beginning of the 20th century. It presents the significance of cardiovascular diseases and addresses major questions currently being discussed among lipidologists and the current thinking with respect to low LDL-cholesterol levels and HDL. It provides an overview of the period during which lipid-modifying drugs were introduced and their relevance with respect to cardiovascular outcome data and lists possible reasons why some patients develop new cardiovascular events while being treated with statins...
November 2017: Atherosclerosis. Supplements
https://www.readbyqxmd.com/read/29095667/pcsk9-inhibitors-mechanisms-of-action-metabolic-effects-and-clinical-outcomes
#12
Connie N Hess, Cecilia C Low Wang, William R Hiatt
Atherosclerotic cardiovascular disease (ASCVD) is associated with significant morbidity and mortality worldwide. Increased serum levels of lowdensity lipoprotein cholesterol (LDL-C) are an independent risk factor for ASCVD, and clinical trial data have shown that lowering LDL-C generally reduces cardiovascular risk. Until recently, 3-hydroxy-3-methylglutarylcoenzyme A (HMG-CoA) reductase inhibitors (statins) have been the main therapy for lowering LDL-C. However, some statin-treated patients have persistently elevated residual cardiovascular risk due to inadequate lowering of LDL-C levels or non-LDL-related dyslipidemia...
November 2, 2017: Annual Review of Medicine
https://www.readbyqxmd.com/read/29093432/european-society-of-cardiology-esc-annual-congress-report-from-barcelona-2017
#13
Kimio Satoh, Jun Takahashi, Yasuharu Matsumoto, Shunsuke Tatebe, Tatsuo Aoki, Yoku Kikuchi, Kiyotaka Hao, Kazuma Ohyama, Masamichi Nogi, Akira Suda, Shintaro Kasahara, Koichi Sato, Sadamitsu Ichijo, Hiroaki Shimokawa
From August 26th to 30th, the 2017 Annual Congress of the European Society of Cardiology (ESC 2017) was held in Barcelona, Spain. Despite the terrorism tradegy just before the ESC congress, the congress attracted many medical professionals from all over the world to discuss the recent topics in cardiovascular medicine in more than 500 sessions, including COMPASS (Cardiovascular OutcoMes for People using Anticoagulation StrategieS Trial), CANTOS (Canakinumab Anti-Inflammatory Thrombosis Outcomes Study), and ORION (which assessed the effect of a novel siRNA inhibitor to PCSK9 on reductions in low-density lipoprotein cholesterol)...
November 2, 2017: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/29078037/the-effects-of-single-and-multiple-dose-administration-of-bococizumab-rn316-pf-04950615-a-humanized-igg2%C3%AE-a-monoclonal-antibody-binding-proprotein-convertase-subtilisin-kexin-type-9-in-hypercholesterolemic-subjects-treated-with-and-without-atorvastatin-results
#14
Barry Gumbiner, Tenshang Joh, Hong Liang, Hong Wan, Matteo Levisetti, Alicia M Vana, David L Shelton, Philippe Forgues, Stephan Billotte, Jaume Pons, Charles M Baum, Pamela D Garzone
AIMS: Three single-dose and one multiple-dose phase I studies were conducted in subjects with primary hypercholesterolemia to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of bococizumab, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor. METHODS: The dosing schedules for hypercholesterolemic subjects randomized in the four phase I studies were: 1) ascending, single, intravenous (IV) bococizumab (0.3, 1, 3, 6, 12, or 18 mg/kg) or placebo (N=48; baseline low-density lipoprotein cholesterol [LDL-C] ≥130 mg/dL); 2) single, IV bococizumab (0...
October 27, 2017: Cardiovascular Therapeutics
https://www.readbyqxmd.com/read/29073340/liver-targeted-small-molecule-inhibitors-of-proprotein-convertase-subtilisin-kexin-type-9-synthesis
#15
Kim Francis McClure, David W Piotrowski, Donna Petersen, Liuqing Wei, Jun Xiao, Allyn T Londregan, Adam Kamlet, Anne-Marie Dechert-Schmitt, Brian Raymer, Roger B Ruggeri, Daniel Canterbury, Chris Limberakis, Spiros Liras, Paul DaSilva-Jardine, Robert G Dullea, Paula M Loria, Benjamin Reidich, Christopher T Salatto, Heather Eng, Emi Kimoto, Karen Atkinson, Amanda King-Ahmad, Dennis Scott, Kevin Beaumont, Jeffrey R Chabot, Michael Bolt, Kevin Maresca, Kenneth Dahl, Ryosuke Arakawa, Akihiro Takano, Christer Halladin
Targeting of the human ribosome is an unprecedented therapeutic modality with a genome-wide selectivity challenge. Herein we describe a liver-targeted drug candidate that inhibits ribosomal synthesis of PCSK9, a lipid regulator considered undruggable by small molecules. Key to the concept was the identification of pharmacologically active zwitterions designed to be retained in the liver. Oral delivery of the poorly permeable zwitterions was achieved via prodrugs susceptible to cleavage by carboxylesterase 1...
October 26, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/29069377/effect-of-statins-and-non-statin-ldl-lowering-medications-on-cardiovascular-outcomes-in-secondary-prevention-a-meta-analysis-of-randomized-trials
#16
Konstantinos C Koskinas, George C M Siontis, Raffaele Piccolo, Dimitris Mavridis, Lorenz Räber, François Mach, Stephan Windecker
Aims: Current evidence on dyslipidaemia management has expanded to novel treatments and very low achieved levels of low-density lipoprotein cholesterol (LDL-C). We sought to compare the clinical impact of more-intensive vs. less-intensive LDL-C lowering by means of statins and currently recommended non-statin medications in secondary prevention. Methods and results: We searched Medline, EMBASE, and Cochrane databases for randomized controlled trials of statins, ezetimibe, proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors, or bile acid sequestrants with >500 patients followed for ≥1 year...
October 23, 2017: European Heart Journal
https://www.readbyqxmd.com/read/29058944/statin-drug-interactions-and-related-adverse-reactions-an-update
#17
Stefano Bellosta, Alberto Corsini
Statins reduce the risk of cardiovascular morbidity and mortality in patients with or at risk for cardiovascular disease and their use is expanding, especially in elderly. Statins are prescribed on a long-term basis and may undergo drug-drug interactions (DDIs) with other drugs. Statins have different safety and tolerability, and this might affect the possibility of DDIs with other cardiovascular drugs, increasing the risk of statin-associated myopathy and hepatotoxicity. Polypharmacy and pharmacogenetic variability are potential causes of statin DDIs...
October 30, 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/29057618/effects-of-12-weeks-of-treatment-with-intravenously-administered-bococizumab-a-humanized-monoclonal-antibody-blocking-proprotein-convertase-subtilisin-kexin-type-9-in-hypercholesterolemic-subjects-on-high-dose-statin
#18
Sergio Fazio, David G Robertson, Tenshang Joh, Hong Wan, Tom Riel, Philippe Forgues, Charles M Baum, Pamela D Garzone, Barry Gumbiner
AIMS: Two multiple-dose phase II studies were conducted in subjects with primary hypercholesterolemia to evaluate the LDL-C lowering efficacy, safety, and tolerability of bococizumab, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor. METHODS: The results from the two phase II, double-blinded, randomized, placebo-controlled, multicenter studies conducted in the USA and Canada were combined. In Study 1, 90 subjects with LDL-C ≥100 mg/dL received intravenous (IV) placebo or bococizumab 0...
October 23, 2017: Cardiovascular Therapeutics
https://www.readbyqxmd.com/read/29056268/successful-treatment-of-a-patient-with-statin-induced-myopathy-and-myotonic-dystrophy-type-ii-with-proprotein-convertase-subtilisin-kexin-type-9-inhibitor-alirocumab-praluent
#19
Mohamed K M Shakir, Terry Shin, Thanh D Hoang, Vinh Q Mai
Presently there are limited treatment options for hypercholesterolemia in patients with statin intolerance and myotonic dystrophy. A 74 year-old male presented to endocrine clinic with hypercholesterolemia (serum LDL-C 210 mg/dL), hypogonadism, insulin-controlled type 2 diabetes mellitus, and minimally elevated serum creatine kinase (CK) levels (184 U/L, ref. range 38-174). Shortly after simvastatin treatment, patient developed severe myalgias in the proximal lower and upper extremities; and serum CK increased to 317 U/L...
September 4, 2017: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/29049827/cost-effectiveness-of-pcsk9-inhibitors-proof-in-the-modeling
#20
Robert O Bonow, Robert A Harrington, Clyde W Yancy
No abstract text is available yet for this article.
October 18, 2017: JAMA Cardiology
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