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https://www.readbyqxmd.com/read/29096860/current-insights-into-the-german-lipoprotein-apheresis-standard-pcsk9-inhibitors-lipoprotein-apheresis-or-both
#1
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/29096851/how-effectively-will-pcsk9-inhibitors-allow-retrieval-of-freedom-from-apheresis-in-cardiovascular-high-risk-patients-estimates-form-a-large-single-center
#2
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/28994502/pro-protein-subtilisin-kexin-9-pcsk9-inhibition-in-practice-lipid-clinic-experience-in-2-contrasting-uk-centres
#3
Monika Kohli, Kinjal Patel, Zofia MacMahon, Radha Ramachandran, Martin A Crook, Timothy M Reynolds, Anthony S Wierzbicki
BACKGROUND: Prescribing criteria have been suggested for proprotein convertase subtilisin kexin-9 (PCSK-9) inhibitors but few studies exist of their real-world effectiveness. METHODS: This study audited PCSK-9 inhibitor therapy in 105 consecutive patients from two hospital centres-a university hospital (UH; n = 70) and a district general hospital (DGH; n = 35). Baseline characteristics including cardiovascular disease risk factors, NICE qualification criteria, efficacy and side effects were assessed...
October 10, 2017: International Journal of Clinical Practice
https://www.readbyqxmd.com/read/28964708/ldl-apheresis-in-japan
#4
REVIEW
Hisashi Makino, Tamiko Tamanaha, Mariko Harada-Shiba
LDL apheresis has been developed as the treatment for refractory familial hypercholesterolemia (FH). Currently, plasma exchange, double membrane filtration, and selective LDL adsorption are available in Japan, and selective LDL adsorption is most common method. LDL apheresis can prevent atherosclerosis progression even in homozygous (HoFH). However, in our observational study, HoFH who started LDL apheresis from adulthood had poor prognosis compared with patients who started from childhood. Therefore, as far as possible, HoFH patients need to start LDL apheresis from childhood...
August 31, 2017: Transfusion and Apheresis Science
https://www.readbyqxmd.com/read/28854318/tying-reimbursement-to-outcomes-is-an-ideal-strategy-for-pcsk9-inhibitors
#5
Daniel M Blumenthal, Dana Goldman, Anupam B Jena
No abstract text is available yet for this article.
October 1, 2017: JAMA Cardiology
https://www.readbyqxmd.com/read/28831261/real-world-use-of-pcsk-9-inhibitors-by-early-adopters-cardiovascular-risk-factors-statin-co-treatment-and-short-term-adherence-in-routine-clinical-practice
#6
Kathleen A Fairman, Lindsay E Davis, David A Sclar
BACKGROUND: Inconsistency of real-world medication use with labeled indications may affect cost and clinical value of pharmacotherapy. PCSK-9 inhibitors are labeled in the US for use with statins to reduce low-density lipoprotein cholesterol in patients with atherosclerotic cardiovascular disease (ASCVD) or familial hypercholesterolemia (FH). OBJECTIVE: To assess consistency with labeled indications and treatment persistency for early (first 5 post-launch months) adopters of PCSK-9 inhibitor pharmacotherapy...
2017: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/28777095/pcsk-9-gain-of-function-mutations-r496w-and-d374y-and-clinical-cardiovascular-characteristics-in-a-cohort-of-turkish-patients-with-familial-hypercholesterolemia
#7
Esra Kaya, Meral Kayıkçıoğlu, Aslı Tetik Vardarlı, Zuhal Eroğlu, Serdar Payzın, Levent Can
OBJECTIVE: The molecular basis of the mutations in the PCSK9 gene that produces familial hypercholesterolemia (FH) in the Turkish population is unknown. This study was conducted to determine the presence of four different PCSK9 gain-of-function (GOF) mutations (F216L, R496W, S127R, and D374Y) in a group of patients with FH. METHODS: A total of 80 consecutive patients with FH (mean age: 56±11 years; mean maximum LDL cholesterol: 251±76 mg/dL) were included in the study...
October 2017: Anatolian Journal of Cardiology
https://www.readbyqxmd.com/read/28709786/-pcsk-9-inhibitors-effects-on-ldl-c-and-future-implications-what-you-should-know
#8
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...
October 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
#9
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
#10
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
#11
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
#12
REVIEW
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...
September 15, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28412198/potential-role-of-lycopene-in-targeting-proprotein-convertase-subtilisin-kexin-type-9-to-combat-hypercholesterolemia
#13
Sahir Sultan Alvi, Irfan A Ansari, Imran Khan, Johar Iqbal, M Salman Khan
Proprotein convertase subtilisin/kexin type 9 (PCSK-9) is a serine protease of the proprotien convertase (PC) family that has profound effects on plasma low density lipoprotein cholesterol (LDL-C) levels, the major risk factor for coronary heart disease (CHD), through its ability to mediate LDL receptor (LDL-R) protein degradation and reduced recycling to the surface of hepatocytes. Thus, the current study was premeditated not only to evaluate the role of lycopene in targeting the inhibition of PCSK-9 via modulation of genes involved in cholesterol homeostasis in HFD rats but also to examine a correlation between HFD induced inflammatory cascades and subsequent regulation of PCSK-9 expression...
April 12, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28289523/pcsk9-inhibitors-a-new-era-of-lipid-lowering-therapy
#14
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
#15
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/27771416/candidate-gene-analysis-of-the-fibrinogen-phenotype-reveals-the-importance-of-polygenic-co-regulation
#16
H Toinét Cronjé, Cornelie Nienaber-Rousseau, Lizelle Zandberg, Tinashe Chikowore, Zelda de Lange, Tertia van Zyl, Marlien Pieters
Fibrinogen and its functional aspects have been linked to cardiovascular disease. There is vast discrepancy between the heritability of fibrinogen concentrations observed in twin studies and the heritability uncovered by genome wide association studies. We postulate that some of the missing heritability might be explained by the pleiotropic and polygenic co-regulation of fibrinogen through multiple targeted genes, apart from the fibrinogen genes themselves. To this end we investigated single nucleotide polymorphisms (SNPs) in genes coding for phenotypes associated with total and γ' fibrinogen concentrations and clot properties...
July 2017: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/27747489/current-consensus-and-controversies-in-guidelines-for-lipid-and-hypertension-management-in-diabetes
#17
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/27662822/the-anti-adipogenic-effect-of-peripheral-blood-mononuclear-cells-is-absent-with-pcsk9-loss-of-function-variants
#18
AnneMarie Gagnon, Teik C Ooi, Marion Cousins, Colette Favreau, Kathy Henry, Anne Landry, Alexander Sorisky
OBJECTIVE: To determine the effect of (1) an oral fat load and (2) pro-protein convertase subtilisin/kexin type (PCSK) 9 loss-of-function (LOF) variant status on the ability of peripheral blood mononuclear cells (PBMC) to inhibit human adipogenesis. METHODS: PBMC from subjects with one or more PCSK9 LOF variants versus non-variant controls were compared in the fasting state and after an oral fat load. RESULTS: Fasting triglyceride (TG) levels were lower in the LOF variant versus non-variant group but rose to the same level after the oral fat load...
November 2016: Obesity
https://www.readbyqxmd.com/read/27424187/evaluation-of-a-new-genetic-epidemiology-resource-the-intermountain-genealogy-registry
#19
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
#20
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
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