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https://www.readbyqxmd.com/read/28709786/-pcsk-9-inhibitors-effects-on-ldl-c-and-future-implications-what-you-should-know
#1
P Corral, A J Ruiz
The discovery of proprotein convertase subtilisin/kexin type 9 (PCSK9) in 2003 in families with familial hypercholesterolemia (HF) later generated the development of pharmacological strategies in order to inhibit this protein. Twelve years after this discovery, the first two biological compounds (monoclonal antibodies) were approved, which have been shown to substantially decrease LDL-C and other lipid subfractions. The objective of the present article is to review the history of the discovery of PCSK9, its physiology and pathophysiology and subsequent pharmacological development...
July 11, 2017: Hipertensión y Riesgo Vascular
https://www.readbyqxmd.com/read/28555526/statin-intolerance-in-heterozygous-familial-hypercolesterolemia-with-cardiovascular-disease-after-pcsk-9-antibodies-what-else
#2
Francesco Sbrana, Beatrice Dal Pino, Federico Bigazzi, Andrea Ripoli, Claudio Passino, Alessandra Gabutti, Emilio M Pasanisi, Christina Petersen, Alessandro Valleggi, Giancarlo Todiere, Andrea Barison, Alberto Giannoni, Luca Panchetti, Francesco Becherini, Mascia Pianelli, Roberta Luciani, Tiziana Sampietro
Background Familial hypercholesterolemia is the elective clinical condition that deserves the maximal personalisation in lipid-lowering therapy, especially in the presence of statin intolerance. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors represent a promising approach to lower low-density lipoprotein (LDL) cholesterol. Methods We enrolled 18 patients (mean age 62 ± 8 years, 72% men) affected by heterozygous familial hypercholesterolemia and cardiovascular disease, with a history of statin intolerance assigned to PCSK9 inhibitors...
January 1, 2017: European Journal of Preventive Cardiology
https://www.readbyqxmd.com/read/28500517/role-of-non-statins-ldl-c-thresholds-and-special-population-considerations-a-look-at-the-updated-2016-acc-consensus-committee-recommendations
#3
REVIEW
Bhavin B Adhyaru, Terry A Jacobson
PURPOSE OF REVIEW: The 2013 ACC/AHA Cholesterol guidelines was a major paradigm shift in the management and treatment of dyslipidemia. The new guidelines outlined "statin benefit groups," highlighted weighing the benefit versus risks of statin therapy ("net benefit"), and discussed the importance of shared decision making between patients and providers in primary prevention. While there was widespread agreement on the main groups benefiting from statin therapy, there was significant controversy regarding LDL-C goals and thresholds, the role of non-statin therapy, and the use of statins in specific populations...
June 2017: Current Atherosclerosis Reports
https://www.readbyqxmd.com/read/28471246/why-published-studies-of-the-cost-effectiveness-of-pcsk-9-inhibitors-yielded-such-markedly-different-results
#4
Peter P Toth, Warren Stevens, Jacquelyn W Chou
No abstract text is available yet for this article.
July 2017: Journal of Medical Economics
https://www.readbyqxmd.com/read/28456517/proprotein-convertase-inhibition-paralyzing-the-cell-s-master-switches
#5
Andres J Klein-Szanto, Daniel E Bassi
Proprotein convertases are serine proteases responsible for the cleavage and subsequent activation of protein substrates, many of them relevant for the development of an ample variety of diseases. Seven of the PCs, including furin and PACE4, recognize and hydrolyze the C-terminal end of the general sequence RXRR/KXR, whereas PCSK-9 recognizes a series of non-basic amino acids. In some systems, PC-mediated substrate activation results in the development of pathological processes, such as cancer, endocrinopathies, and cardiovascular and infectious diseases...
April 27, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28289523/pcsk9-inhibitors-a-new-era-of-lipid-lowering-therapy
#6
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/28032426/lipoprotein-a-in-postmenopausal-women-assessment-of-cardiovascular-risk-and-therapeutic-options
#7
REVIEW
Panagiotis Anagnostis, Spyridon Karras, Irene Lambrinoudaki, John C Stevenson, Dimitrios G Goulis
INTRODUCTION: Lipoprotein(a) [Lp(a)], a low-density lipoprotein (LDL)-like particle, has been independently associated with increased cardiovascular disease (CVD) risk in various populations, such as postmenopausal women. The purpose of this narrative review is to present current data on the role of Lp(a) in augmenting CVD risk in postmenopausal women and focus on the available therapeutic strategies. METHODS: PubMed was searched for English language publications until November 2015 under the following terms: "therapy" OR "treatment" AND ["lipoprotein (a)" OR "Lp(a)"] AND ("postmenopausal women" OR "menopausal women" OR "menopause")...
December 2016: International Journal of Clinical Practice
https://www.readbyqxmd.com/read/27747489/current-consensus-and-controversies-in-guidelines-for-lipid-and-hypertension-management-in-diabetes
#8
Om P Ganda, Joanna Mitri
Despite major advances, many patients with diabetes are currently achieving suboptimal control of lipids and blood pressure. The new cholesterol guidelines by the ACC/AHA have reignited the emphasis on more intensive treatment with statins in the population at high risk of CVD, including those with diabetes. While these guidelines do not include specific lipid goals, several other guidelines have retained previously defined risk-based LDL-C and non-HDL-C goals. More recent data indicate potential benefits in CVD outcomes with non-statin therapy added to statin therapy...
November 2016: Current Cardiology Reports
https://www.readbyqxmd.com/read/27424187/evaluation-of-a-new-genetic-epidemiology-resource-the-intermountain-genealogy-registry
#9
Stacey Knight, Arthur T Maness, Sue M Dintelman, Benjamin D Horne
BACKGROUND: Many landmark genetic breakthroughs, including the recent discovery of PCSK-9 inhibitor drugs, were accomplished with substantial contributions from evaluation of pedigrees. Finding and ascertaining high-value pedigrees is not trivial and requires considerable time and cost. Here, we describe the creation of the Intermountain Genealogy Registry for use in studying the genetics of cardiovascular and other diseases. METHODS: Using publicly available pedigree records and probabilistic linkage techniques, we created a genealogy of ≈23 million records that we linked to 3...
2016: Human Heredity
https://www.readbyqxmd.com/read/27096698/the-new-face-of-hyperlipidemia-management-proprotein-convertase-subtilisin-kexin-inhibitors-pcsk-9-and-their-emergent-role-as-an-alternative-to-statin-therapy
#10
REVIEW
Lillian Smith, Juan Mosley, Jarah Yates, Luke Caswell
This review analyzes Proprotein Convertase Subtilisin/Kexin 9 inhibitors (PCSK-9), a new medication class that has arisen in the last year to combat hypercholesterolemia. They are targeted towards patients who are unable to achieve acceptable low density lipoprotein (LDL) levels despite maximum statin therapy, as well as those who are unable to tolerate maximum statin therapy due to side effects such as myopathy or myalgia. Two of these medications have been released in the last year: alirocumab (Praluent) and evolocumab (Repatha)...
2016: Journal of Pharmacy & Pharmaceutical Sciences: a Publication of the Canadian Society for Pharmaceutical Sciences
https://www.readbyqxmd.com/read/26547456/predicting-the-overuse-of-pcsk-9-inhibitors
#11
Rene Rodriguez-Gutierrez, Nilay D Shah, Victor M Montori
No abstract text is available yet for this article.
November 10, 2015: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/26545013/atherosclerosis-stabilization-with-pcsk-9-inhibition-an-evolving-concept-for-cardiovascular-prevention
#12
Jennifer G Robinson, Donald D Heistad, Keith A A Fox
Monoclonal antibodies (mAbs) to proprotein convertase subtilisin/kexin type 9 (PCSK-9) can further lower LDL-C by ≥60% in statin-treated patients. Preliminary data suggest they may reduce cardiovascular (CVD) events. Ongoing PCSK-9 mAb cardiovascular outcomes trials could provide the opportunity to determine whether a "legacy effect" similar to that observed for statins will occur over the post-trial observation period. We hypothesize these trials could demonstrate that (1) very aggressive LDL-C lowering with PCSK-9 mAbs added to background statin therapy will induce extensive atherosclerosis stabilization and regression in the large majority of treated patients, and (2) continued maintenance therapy with high intensity statin therapy (with or without ezetimibe) should then inhibit new plaque formation, with a long-term prevention of CVD events...
December 2015: Atherosclerosis
https://www.readbyqxmd.com/read/26135857/discovery-approaches-for-novel-dyslipidemia-drugs
#13
REVIEW
Faheem Maqbool, Malihe Safavi, Haji Bahadar, Mahban Rahimifard, Kamal Niaz, Mohammad Abdollahi
INTRODUCTION: Dyslipidemia is increased fasting level of total cholesterol (TC), LDL cholesterol (LDL-C), and triglycerides (TG), along with decreased levels of HDL cholesterol (HDL-C). Owing to effect on the cardiovascular system and increased chances of metabolic diseases, it is needed to review novel under development drugs and new approaches in drug discovery for dyslipidemia. AREAS COVERED: This article reviews all phases I to IV clinical trials and preclinical trials with results associated with novel treatment of dyslipidemia...
2015: Current Drug Discovery Technologies
https://www.readbyqxmd.com/read/25600043/-familial-hypercholesterolemia-past-and-present-my-experiences-and-findings-in-our-group-of-patients-with-familial-hypercholesterolemia
#14
Richard Češka, Michal Vrablík, Tereza Altschmiedová, Martina Prusíková, Zuzana Urbanová, Josef Šobra
Currently, the familial hypercholesterolemia (FH) rises the interest. The reason is that this genetic disorder is targeted by newly emerged and highly effective hypolipidemic agents, PCSK-9 inhibitors, lomitapid and mipomersen. Present paper discusses 2 patient study groups, before 50 years and nowadays. Although direct statistical analysis is impossible some changes in clinical features of FH might be found over the course of the time. In fact, the basic FH characteristic has not changed dramatically. Severe isolated hypercholesterolemia with total cholesterol 9-10 mmol/l, LDL-cholesterol 7-8 mmol/l and normal values of triglycerides dominates in laboratory analysis...
November 2014: Vnitr̆ní Lékar̆ství
https://www.readbyqxmd.com/read/25468918/dyslipidaemia-what-s-around-the-corner
#15
Anthony S Wierzbicki, Dilinika Perera, Mfon Ewang-Emukowhate
Hyperlipidaemia is a major risk factor for the development of atherosclerosis and cardiovascular disease. Statins are the mainstay of therapy and new guidelines focus on the use of these agents without specific targets for low-density lipoprotein (LDL)-cholesterol or non high-density lipoprotein (HDL)-cholesterol. However, patients remain at risk of cardiovascular disease despite statin therapy so new drugs are required. This article reviews therapies in development to further lower LDL-cholesterol (Proprotein convertase subtilisin/kexin-9 (PCSK-9) inhibitors), raise HDL-holesterol (cholesterol ester transfer protein inhibitors (CETPIs)) and reduce triglycerides (novel peroxisome proliferator-activated receptor (PPAR)-agonists and omega-3 fatty acid preparations)...
December 2014: Clinical Medicine: Journal of the Royal College of Physicians of London
https://www.readbyqxmd.com/read/25257073/what-are-we-able-to-achieve-today-for-our-patients-with-homozygous-familial-hypercholesterolaemia-and-what-are-the-unmet-needs
#16
REVIEW
Raul D Santos
Homozygous familial hypercholesterolaemia (HoFH) is a rare, life-threatening disease characterised by highly elevated low-density lipoprotein cholesterol levels (LDL-C), cutaneous and tendinous xanthomata, severe and precocious atherosclerosis, and aortic and supra aortic valve disease. Although treatment with apheresis and lipid-lowering drugs has improved event-free survival of HoFH patients, the condition is still associated with early onset cardiovascular disease and death due to residual high cholesterol levels...
September 2014: Atherosclerosis. Supplements
https://www.readbyqxmd.com/read/23735860/when-should-we-measure-lipoprotein-a
#17
REVIEW
Karam M Kostner, Winfried März, Gerhard M Kostner
Recently published epidemiological and genetic studies strongly suggest a causal relationship of elevated concentrations of lipoprotein (a) [Lp(a)] with cardiovascular disease (CVD), independent of low-density lipoproteins (LDLs), reduced high density lipoproteins (HDL), and other traditional CVD risk factors. The atherogenicity of Lp(a) at a molecular and cellular level is caused by interference with the fibrinolytic system, the affinity to secretory phospholipase A2, the interaction with extracellular matrix glycoproteins, and the binding to scavenger receptors on macrophages...
November 2013: European Heart Journal
https://www.readbyqxmd.com/read/22935039/the-localization-and-regulation-of-proprotein-convertase-subtilisin-kexin-pcsk-6-in-human-ovary
#18
Ikumi Akiyama, Osamu Yoshino, Yutaka Osuga, Jia Shi, Yasushi Hirota, Tetsuya Hirata, Miyuki Harada, Kaori Koga, Akihisa Fujimoto, Tetsu Yano, Yuji Taketani
PROBLEM: The aim of this study is to evaluate the expression and regulation of proprotein convertase subtilisin/kexin (PCSK) 6, which is known to be an important factor in the production of bone morphogenetic protein (BMP) cytokines in human ovary. METHOD OF STUDY: The localization of PCSK 6 protein in normal human ovaries was examined by immunohistochemistry. Human granulosa cells (GC), obtained from 34 patients undergoing ovarian stimulation for in vitro fertilization, were cultured with BMP-2, BMP-6, BMP-7, BMP-15, growth differentiation factor (GDF)-9, and activin-A with or without FSH...
December 2012: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/22493980/inhibition-of-pro-protein-convertase-subtilisin-kexin-9-corrected-pcsk-9-as-a-treatment-for-hyperlipidaemia
#19
REVIEW
Anthony S Wierzbicki, Timothy C Hardman, Adie Viljoen
INTRODUCTION: Pro-protein [corrected] convertase subtilisin kexin (PCSK)-9 is a newly discovered protein involved in intracellular and extracellular regulation of low-density lipoprotein receptor (LDLR) expression. Autosomal dominant activating mutations in PCSK-9 cause familial hypercholesterolaemia whereas inactivating mutations in man reduce LDL cholesterol (LDL-C) and are associated with a decreased lifetime risk of cardiovascular events. AREAS COVERED: As PCSK-9 binds to the LDLR, a number of approaches involving small molecule or peptide inhibition of binding, antibody-mediated inactivation of binding and the use of antisense oligonucleotides are being investigated as therapeutic approaches to lower LDL-C in man...
May 2012: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/21476974/lipoprotein-a-medical-treatment-options-for-an-elusive-molecule
#20
REVIEW
Klaus G Parhofer
Elevated levels of lipoprotein(a) are causally related to premature atherosclerosis. It is therefore of interested to evaluate by which treatment modalities elevated lipoprotein(a) levels can be decreased. With the exception of niacin, currently available lipid modifying drugs have only little effect on lipoprotein(a) levels. Niacin can decrease lipoprotein(a) concentration in a dose dependent fashion by approximately 20-30%. Similarly, acetylsalicylic acid and L-carnitine as well as some medications in development (mipomersen, eprotirome, Proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors, Cholesterol-ester-transfer protein (CETP inhibitors) can decrease elevated lipoprotein(a) concentrations...
2011: Current Pharmaceutical Design
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