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https://www.readbyqxmd.com/read/28341307/the-efficacy-advantage-of-evolocumab-amg-145-dosed-at-140mg-every-2weeks-versus-420mg-every-4weeks-in-patients-with-hypercholesterolemia-evidence-from-a-meta-analysis
#1
Xiao-Xiao He, Rong Zhang, Pei-Yuan Zuo, Yu-Wei Liu, Xiang-Nan Zha, Sheng-Shuai Shan, Cheng-Yun Liu
BACKGROUND: Evolocumab (AMG 145), a PCSK9 inhibitor, has been shown to decrease low-density lipoprotein cholesterol (LDL-C) levels. Doses of 140mg administered every 2weeks (Q2W) and 420mg administered every 4weeks (Q4W) are widely used, and both dosing schedules were effective in clinical trials. However, some researchers have speculated that 140mg Q2W administration has equal or even greater efficacy. This meta-analysis was performed to assess the differences in efficacy and safety between the two doses...
March 2017: European Journal of Internal Medicine
https://www.readbyqxmd.com/read/28329241/lipoprotein-a-the-revenant
#2
Baris Gencer, Florian Kronenberg, Erik S Stroes, François Mach
In the mid-1990s, the days of lipoprotein(a) [Lp(a)] were numbered and many people would not have placed a bet on this lipid particle making it to the next century. However, genetic studies brought Lp(a) back to the front-stage after a Mendelian randomization approach used for the first time provided strong support for a causal role of high Lp(a) concentrations in cardiovascular disease and later also for aortic valve stenosis. This encouraged the use of therapeutic interventions to lower Lp(a) as well numerous drug developments, although these approaches mainly targeted LDL cholesterol, while the Lp(a)-lowering effect was only a 'side-effect'...
February 17, 2017: European Heart Journal
https://www.readbyqxmd.com/read/28328015/pcsk9-inhibitor-access-barriers-issues-and-recommendations-improving-the-access-process-for-patients-clinicians-and-payers
#3
REVIEW
Seth J Baum, Peter P Toth, James A Underberg, Paul Jellinger, Joyce Ross, Katherine Wilemon
The proprotein convertase subtilisin/kexin type 9 inhibitors or monoclonal antibodies likely represent the greatest advance in lipid management in 30 years. In 2015 the US Food and Drug Administration approved both alirocumab and evolocumab for high-risk patients with familial hypercholesterolemia (FH) and clinical atherosclerotic cardiovascular disease requiring additional lowering of low-density lipoprotein cholesterol. Though many lipid specialists, cardiovascular disease prevention experts, endocrinologists, and others prescribed the drugs on label, they found their directives denied 80% to 90% of the time...
March 22, 2017: Clinical Cardiology
https://www.readbyqxmd.com/read/28325524/current-status-of-lipid-management-in-acute-coronary-syndrome
#4
REVIEW
Koichiro Fujisue, Kenichi Tsujita
The development of coronary revascularization has dramatically improved early cardiovascular outcomes in patients with acute coronary syndrome (ACS). However, patients who have experienced myocardial infarction (MI) are at high risk of recurrence of cardiovascular events compared with those who are healthy or have stable coronary artery disease. Acute coronary events induce further inflammatory responses and plaque vulnerability in either a coronary culprit or whole vessels. The majority of data have supported the importance of coronary risk management to prevent secondary events...
March 18, 2017: Journal of Cardiology
https://www.readbyqxmd.com/read/28304242/cardiovascular-efficacy-and-safety-of-bococizumab-in-high-risk-patients
#5
Paul M Ridker, James Revkin, Pierre Amarenco, Robert Brunell, Madelyn Curto, Fernando Civeira, Marcus Flather, Robert J Glynn, Jean Gregoire, J Wouter Jukema, Yuri Karpov, John J P Kastelein, Wolfgang Koenig, Alberto Lorenzatti, Pravin Manga, Urszula Masiukiewicz, Michael Miller, Arend Mosterd, Jan Murin, Jose C Nicolau, Steven Nissen, Piotr Ponikowski, Raul D Santos, Pamela F Schwartz, Handrean Soran, Harvey White, R Scott Wright, Michal Vrablik, Carla Yunis, Charles L Shear, Jean-Claude Tardif
Background Bococizumab is a humanized monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9) and reduces levels of low-density lipoprotein (LDL) cholesterol. We sought to evaluate the efficacy of bococizumab in patients at high cardiovascular risk. Methods In two parallel, multinational trials with different entry criteria for LDL cholesterol levels, we randomly assigned the 27,438 patients in the combined trials to receive bococizumab (at a dose of 150 mg) subcutaneously every 2 weeks or placebo...
March 17, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28295777/can-ldl-cholesterol-be-too-low-possible-risks-of-extremely-low-levels
#6
Anders G Olsson, Bo Angelin, Gerd Assmann, Christoph J Binder, Ingemar Björkhem, Angel Cedazo-Minguez, Jonathan Cohen, Arnold von Eckardstein, Eduardo Farinaro, Dirk Müller-Wieland, Klaus G Parhofer, Paolo Parini, Robert S Rosenson, Jakob Starup-Linde, Matti J Tikkanen, Laurent Yvan-Charvet
Following the continuous accumulation of evidence supporting the beneficial role of reducing low-density lipoprotein cholesterol (LDL-C) levels in the treatment and prevention of atherosclerotic cardiovascular disease and its complications, therapeutic possibilities now exist to lower LDL-C to very low levels, similar to or even lower than those seen in newborns and nonhuman species. In addition to the important task of evaluating potential side-effects of such treatments, the question arises whether extremely low LDL-C levels per se may provoke adverse effects in humans...
March 14, 2017: Journal of Internal Medicine
https://www.readbyqxmd.com/read/28291870/long-term-low-density-lipoprotein-cholesterol-lowering-efficacy-persistence-and-safety-of-evolocumab-in-treatment-of-hypercholesterolemia-results-up-to-4-years-from-the-open-label-osler-1-extension-study
#7
Michael J Koren, Marc S Sabatine, Robert P Giugliano, Gisle Langslet, Stephen D Wiviott, Helina Kassahun, Andrea Ruzza, Yuhui Ma, Ransi Somaratne, Frederick J Raal
Importance: The Open-Label Study of Long-term Evaluation Against LDL-C (OSLER-1) evaluated the durability of long-term efficacy and safety during long-term therapy with evolocumab, a monoclonal antibody against proprotein convertase subtilisin/kexin type 9 (PCSK9). Objective: To determine whether LDL-C level reductions with evolocumab persist across different populations. Secondary objectives included assessment of adverse events, antidrug antibodies, and factors contributing to treatment discontinuation...
March 14, 2017: JAMA Cardiology
https://www.readbyqxmd.com/read/28291840/a-wild-type-mouse-based-model-for-the-regression-of-inflammation-in-atherosclerosis
#8
Michael Peled, Hitoo Nishi, Ada Weinstock, Tessa J Barrett, Felix Zhou, Alexandra Quezada, Edward A Fisher
Atherosclerosis can be induced by the injection of a gain-of-function mutant of proprotein convertase subtilisin/kexin type 9 (PCSK9)-encoding adeno-associated viral vector (AAVmPCSK9), avoiding the need for knockout mice models, such as low-density lipoprotein receptor deficient mice. As regression of atherosclerosis is a crucial therapeutic goal, we aimed to establish a regression model based on AAVmPCSK9, which will eliminate the need for germ-line genetic modifications. C57BL6/J mice were injected with AAVmPCSK9 and were fed with Western diet for 16 weeks, followed by reversal of hyperlipidemia by a diet switch to chow and treatment with a microsomal triglyceride transfer protein inhibitor (MTPi)...
2017: PloS One
https://www.readbyqxmd.com/read/28289523/pcsk9-inhibitors-a-new-era-of-lipid-lowering-therapy
#9
REVIEW
Rahul Chaudhary, Jalaj Garg, Neeraj Shah, Andrew Sumner
Hyperlipidemia is a well-established risk factor for developing cardiovascular disease (CVD). The recent American College of Cardiology and American Heart Association guidelines on lipid management emphasize treatment of individuals at increased risk for developing CVD events with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) at doses proven to reduce CVD events. However, there are limited options for patients who are either intolerant to statin therapy, develop CVD despite being on maximally tolerated statin therapy, or have severe hypercholesterolemia...
February 26, 2017: World Journal of Cardiology
https://www.readbyqxmd.com/read/28286091/pcsk9-monoclonal-antibodies-in-2016-current-status-and-future-challenges
#10
REVIEW
Hashrul Rashid, Ian T Meredith, Arthur Nasis
Cardiovascular disease remains the leading cause of morbidity and mortality in developed nations, with elevated low-density lipoprotein-cholesterol (LDL-C) levels being a major modifiable risk factor for coronary atherosclerosis. While lipid-lowering therapies such as statins are effective in lowering LDL-C, a proportion of patients do not achieve target LDL-C goals with statins or are intolerant to statins necessitating other treatment options. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are a new class of agents that reduce LDL-C beyond the maximum achievable LDL-C reductions with statins, and have been well studied in different patient groups...
January 23, 2017: Heart, Lung & Circulation
https://www.readbyqxmd.com/read/28283395/proprotein-convertase-subtilisin-kexin-type-9-pcsk9-and-metabolic-syndrome-components-among-young-adult-females
#11
Hayder Hasan, Amita Attlee, Veena Raigangar, Mohamed Madkour, Samir Awadallah
AIMS: Occurrence of metabolic syndrome (MetS) in the United Arab Emirates (UAE) is rising steadily, with subsequent increase in the prevalence of type 2 diabetes and cardiovascular disease (CVD). Recent studies have shown that PCSK9 plays a substantial role in atherogenic dyslipidemia. Hence, the aim of this study was to assess level of PCSK9 and its relationship with MetS components among young adult females. METHODS: This study was carried out on 137 adult females over 18 years of age residing in the UAE...
March 6, 2017: Diabetes & Metabolic Syndrome
https://www.readbyqxmd.com/read/28263403/alternative-treatment-regimens-with-the-pcsk9-inhibitors-alirocumab-and-evolocumab-a-pharmacokinetic-and-pharmacodynamic-modeling-approach
#12
Nina Scherer, Christiane Dings, Michael Böhm, Ulrich Laufs, Thorsten Lehr
Alirocumab and evolocumab are 2 human monoclonal antibodies that inhibit the proprotein convertase subtilisin/kexin type 9 (PCSK9). These antibodies can potently lower low-density lipoprotein cholesterol (LDLc) serum concentrations. The aims of this analysis were to develop a pharmacokinetic (PK) and pharmacodynamic (PD) model for both antibodies, to simulate and investigate different dosage and application regimens, and finally, to note the effects on LDLc levels. Alirocumab was clinically studied and approved with 2 doses, 75 and 150 mg every 2 weeks (Q2W), whereas evolocumab was tested and approved with 2 dosing intervals, 140 mg Q2W and 420 mg Q4W...
March 6, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28260498/treatment-with-proprotein-convertase-subtilisin-kexin-type-9-pcsk9-inhibitors-to-reduce-cardiovascular-inflammation-and-outcomes
#13
Aldo Bonaventura, Federico Carbone, Alessandra Vecchié, Franco Dallegri, Giovanni G Camici, Fabrizio Montecucco, Luca Liberale
Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) is a serine protease involved in cholesterol homeostasis. After binding to the complex low-density lipoprotein (LDL)-receptor, PCSK9 induces its intracellular degradation, thus reducing serum LDL clearance. PCSK9 is mainly secreted by the liver, but it is also expressed to a lesser extent in other organs. Apart from the well-known activity concerning hepatic LDL receptor-mediated pathway, PCSK9 has been supposed to potentially interfere with vascular inflammation in atherogenesis...
March 3, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28242176/2017-taiwan-lipid-guidelines-for-high-risk-patients
#14
REVIEW
Yi-Heng Li, Kwo-Chang Ueng, Jiann-Shing Jeng, Min-Ji Charng, Tsung-Hsien Lin, Kuo-Liong Chien, Chih-Yuan Wang, Ting-Hsing Chao, Ping-Yen Liu, Cheng-Huang Su, Shih-Chieh Chien, Chia-Wei Liou, Sung-Chun Tang, Chun-Chuan Lee, Tse-Ya Yu, Jaw-Wen Chen, Chau-Chung Wu, Hung-I Yeh
In Taiwan, the prevalence of hyperlipidemia increased due to lifestyle and dietary habit changes. Low density lipoprotein cholesterol (LDL-C) and non-high density lipoprotein cholesterol (non-HDL-C) are all significant predicting factors of coronary artery disease in Taiwan. We recognized that lipid control is especially important in patients with existed atherosclerotic cardiovascular diseases (ASCVD), including coronary artery disease (CAD), ischemic stroke and peripheral arterial disease (PAD). Because the risk of ASCVD is high in patients with diabetes mellitus (DM), chronic kidney disease (CKD) and familial hypercholesterolemia (FH), lipid control is also necessary in these patients...
February 24, 2017: Journal of the Formosan Medical Association, Taiwan Yi Zhi
https://www.readbyqxmd.com/read/28222405/thyroid-hormones-a-potential-ally-to-ldl-cholesterol-lowering-agents
#15
REVIEW
Leonidas N Duntas, Gabriela Brenta
L-thyroxine (LT4) treatment of hypothyroidism, particularly in patients with thyroid- stimulating hormone (TSH) >10mU/L, results in improved lipid profile, as LT4 stimulates low-density lipoprotein cholesterol (LDL-C) degradation and the conversion of cholesterol in bile acids by inducing LDL-receptor and 7 alpha hydroxylase expression, respectively. Statins decrease total cholesterol (TC) and LDL-C mainly by suppressing 3-hydroxy-3-methylglutaryl coenzyme A activity. Therefore, the addition of statins to LT4 treatment, following the reversal of hypothyroidism, acts synergistically and forms a powerful treatment modality in patients with this condition whose serum lipids have not achieved the target...
October 2016: Hormones: International Journal of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28215938/limitations-of-cholesterol-lowering-with-pcsk9-inhibitors
#16
Gilbert Thompson
No abstract text is available yet for this article.
February 15, 2017: Lancet Diabetes & Endocrinology
https://www.readbyqxmd.com/read/28215937/long-term-treatment-with-evolocumab-added-to-conventional-drug-therapy-with-or-without-apheresis-in-patients-with-homozygous-familial-hypercholesterolaemia-an-interim-subset-analysis-of-the-open-label-taussig-study
#17
Frederick J Raal, G Kees Hovingh, Dirk Blom, Raul D Santos, Mariko Harada-Shiba, Eric Bruckert, Patrick Couture, Handrean Soran, Gerald F Watts, Christopher Kurtz, Narimon Honarpour, Lihua Tang, Sree Kasichayanula, Scott M Wasserman, Evan A Stein
BACKGROUND: Homozygous familial hypercholesterolaemia is a genetic disorder characterised by substantially raised LDL cholesterol, reduced LDL receptor function, xanthomas, and cardiovascular disease before age 20 years. Conventional therapy is with statins, ezetimibe, and apheresis. We aimed to assess the long-term safety and efficacy of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor evolocumab in a subset of patients with homozygous familial hypercholesterolaemia enrolled in an open-label, non-randomised phase 3 trial...
February 16, 2017: Lancet Diabetes & Endocrinology
https://www.readbyqxmd.com/read/28206704/lipid-lowering-efficacy-and-safety-of-alirocumab-in-patients-with-or-without-diabetes-a-sub-analysis-of-odyssey-combo-ii
#18
Lawrence A Leiter, Jose Luis Zamorano, Maja Bujas-Bobanovic, Michael J Louie, Guillaume Lecorps, Christopher P Cannon, Yehuda Handelsman
AIM: This sub-analysis of the ODYSSEY COMBO II study compared the effects of alirocumab, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, in high cardiovascular risk patients with or without diabetes mellitus (DM) receiving maximally tolerated statin therapy. MATERIALS AND METHODS: COMBO II was a 104-week, double-blind study (n = 720) enrolling patients with documented atherosclerotic cardiovascular disease (ASCVD) and baseline LDL-C ≥70 mg/dL (1...
February 16, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28203441/lipoprotein-a-and-inhibitors-of-proprotein-convertase-subtilisin-kexin-type-9
#19
COMMENT
Kazuhiko Kotani, Maciej Banach
Lipoprotein(a) [Lp(a)] has been identified as a risk factor for cardiovascular disease. Lp(a) levels are also high under certain clinical conditions, including familial hypercholesterolemia and high blood low-density lipoprotein (LDL) cholesterol levels. Few effective generic therapies for modulating Lp(a) have been developed. However, new therapies involving inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9) using monoclonal antibodies have markedly reduced the blood LDL levels-and the Lp(a) levels as well...
January 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28193639/an-endorsement-of-pcsk9-inhibitors-funded-by-%C3%A2-their-manufacturers
#20
Nigel Hawkes
No abstract text is available yet for this article.
February 13, 2017: BMJ: British Medical Journal
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