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https://www.readbyqxmd.com/read/28532784/update-on-the-use-of-pcsk9-inhibitors-in-adults-recommendations-from-an-expert-panel-of-the-national-lipid-association
#1
Carl E Orringer, Terry A Jacobson, Joseph J Saseen, Alan S Brown, Antonio M Gotto, Joyce L Ross, James A Underberg
An Expert Panel convened by the National Lipid Association was charged with updating the recommendations on the use of proprotein convertase subtilisin/kexin type 9 (PCSK9) antibody therapy that were provided by the 2015 National Lipid Association Recommendations for the Patient-Centered Management of Dyslipidemia: Part 2. Recent studies have demonstrated the efficacy of these agents in reducing low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol and have confirmed their excellent safety profile...
May 19, 2017: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/28531826/how-many-familial-hypercholesterolemia-patients-are-eligible-for-pcsk9-inhibition
#2
Luis Masana, Nuria Plana, Sofia Pérez-Calahorra, Daiana Ibarretxe, Itziar Lamiquiz-Moneo, Juan Pedro-Botet, Manuel Suárez-Tembra, Pedro Valdivielso, Emilio Ortega, Fernando Civeira
BACKGROUND AND AIMS: Familial hypercholesterolemia (FH) is a high cardiovascular risk condition. Less than 20% of patients achieve the LDL targets. Although PCSK9 inhibitors improve control and reduce cardiovascular events, official recommendations for their use are restrictive. We aim to assess the number of FH patients suitable for PCSK9 inhibition according to the European guidelines. METHODS: A total of 2685 FH patients, with a minimum follow-up of 6 months, included in the Dyslipidemia Registry of the Spanish Arteriosclerosis Society, were sorted according to the intensity of their lipid-lowering therapy (LLT) and LDL cholesterol levels achieved...
May 12, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28529918/advances-in-dyslipidemia-management-for-prevention-of-atherosclerosis-pcsk9-monoclonal-antibody-therapy-and-beyond
#3
REVIEW
Nathan D Wong, Paul D Rosenblit, Robert S Greenfield
In 2003, select families with familial hypercholesterolemia were first identified to have gain-of-function mutations for proprotein convertase subtilisin kexin type 9 (PCSK9) followed, in 2006, by the identification of those with lifelong low levels of LDL-C and lowered atherosclerotic cardiovascular disease (ASCVD) risk who had loss-of-function PCSK9 mutations. These discoveries led to the rapid development of PSCK9-targeted monoclonal antibody (PCSK9 mAb) therapies and, in 2015, 2 'fully-humanized' PCSK9 mAbs (alirocumab and evolocumab) were marketed in the United States, Europe, and other countries...
April 2017: Cardiovascular Diagnosis and Therapy
https://www.readbyqxmd.com/read/28527325/dyslipidemia-management-update
#4
REVIEW
Yingzi Chang, Jacques Robidoux
Association of hypercholesterolemia and atherosclerotic cardiovascular disease (ASCVD) is well established. Reducing low-density lipoprotein-cholesterol (LDL-C) and raising high-density lipoprotein-cholesterol (HDL-C) have been the therapeutic targets to reduce the risk of ASCVD. Cholesterol-lowering medications have been used to provide both primary and secondary prevention of ASCVD for many years by reducing the absorption and reabsorption, promoting excretion, or decreasing the synthesis of cholesterol. Within the past five years, several new classes of cholesterol-lowering drugs have been tested and approved for patients with hypercholesterolemia that are not well controlled by conventional therapy (ezetimibe, bile-acid sequestrants, and statins)...
May 17, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28509674/evidence-for-more-intensive-cholesterol-lowering
#5
Handrean Soran, See Kwok, Safwaan Adam, Jan Hoong Ho, Paul N Durrington
PURPOSE OF REVIEW: In randomized clinical trials, reduction in cardiovascular disease (CVD) risk with cholesterol-lowering drugs correlates with the LDL cholesterol decrease. However, because the majority have investigated a fixed statin dose, current guidelines disagree about the use of statin dose titration or non-statin adjunctive cholesterol-lowering drugs. RECENT FINDINGS: We conducted a meta-analysis of all randomized controlled trials with CVD end-points, comparing two intensities of lipid-lowering regimens within the same population, using varying statins doses and/or potency, ezetimibe or PCSK9 inhibitors and compared the observed number of patients needed to be treated for 10 years to prevent one CVD event (NNT) with NNT predicted from trials of predominantly single-dose statin...
May 15, 2017: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/28506389/proprotein-convertase-subtilisin-kexin-9%C3%A2-inhibition-in-patients-with-familial-hypercholesterolemia-initial-clinical-experience
#6
Annette M H Galema-Boers, Mattie J Lenzen, Eric J Sijbrands, Jeanine E Roeters van Lennep
BACKGROUND: Despite optimal lipid-lowering therapy, a minority of patients with familial hypercholesterolemia (FH) reach low-density lipoprotein cholesterol (LDL-c) target goals. In randomized trials, proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors led to impressive LDL-c reductions and a favorable safety profile. However, data about the efficacy and safety outside clinical trials are not available yet. OBJECTIVE: The purpose of the study is to describe efficacy and side effects of PCSK9 inhibitors in FH patients in clinical practice...
May 2017: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/28505047/advances-in-the-management-of-dyslipidemia
#7
June Kampangkaew, Stephen Pickett, Vijay Nambi
PURPOSE OF REVIEW: Cardiovascular disease is the leading cause of morbidity and mortality in the United States and therapies aimed at lipid modification are important for the reduction of cardiovascular risk. There have been many exciting advances in lipid management over the recent years. This review discusses these recent advances as well as the direction of future studies. RECENT FINDINGS: Several recent clinical trials support low-density lipoprotein cholesterol (LDL-c) reduction beyond maximal statin therapy for improved cardiovascular outcomes...
May 12, 2017: Current Opinion in Cardiology
https://www.readbyqxmd.com/read/28492287/dyslipidaemia-pcsk9-inhibitors-and-foamy-monocytes-in-familial-hypercholesterolaemia
#8
Huaizhu Wu, Christie M Ballantyne
No abstract text is available yet for this article.
May 11, 2017: Nature Reviews. Cardiology
https://www.readbyqxmd.com/read/28488460/the-efficacy-of-evolocumab-in-the-management-of-hyperlipidemia-a-systematic-review
#9
Lamia AlHajri, Asma AlHadhrami, Shama AlMheiri, Yalwah AlMutawa, Zainab AlHashimi
BACKGROUND: Hyperlipidemia or dyslipidemia has been a concern for a long time, with various guidelines emphasizing the importance of managing the lipid profile to prevent cardiac incidences. Although statins have been found to be highly effective, resistance and intolerability to side effects will continue to be a stumbling block for certain patients. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors tackle lipid profile via a novel mechanism and therefore provide an additional effective option for managing lipid profile...
May 2017: Therapeutic Advances in Cardiovascular Disease
https://www.readbyqxmd.com/read/28483371/pcsk9-inhibitors-smooth-sailing-or-a-little-turbulence-ahead
#10
Robert A Hegele
No abstract text is available yet for this article.
May 5, 2017: Lancet Diabetes & Endocrinology
https://www.readbyqxmd.com/read/28471634/a-highly-durable-rnai-therapeutic-inhibitor-of-pcsk9
#11
COMMENT
Shigeo Masuda, Shigeru Miyagawa, Yoshiki Sawa
New England Journal of Medicine, Volume 376, Issue 18, May 2017.
May 4, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28467196/pcsk9-inhibitors-a-new-age-in-lipid-management
#12
Peter J Grant
No abstract text is available yet for this article.
May 2017: Diabetes & Vascular Disease Research
https://www.readbyqxmd.com/read/28465286/estimation-of-eligibility-for-pcsk9-inhibitors-and-associated-costs-based-on-the-fourier-trial-insights-from-the-department-of-veterans-affairs
#13
Salim S Virani, Julia M Akeroyd, Vijay Nambi, Paul A Heidenreich, Pamela B Morris, Khurram Nasir, Erin D Michos, Vera A Bittner, Laura A Petersen, Christie M Ballantyne
In the Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER) trial,1 treatment with evolocumab resulted in a 15% relative (1.5% absolute) risk reduction of major cardiovascular events in patients with atherosclerotic cardiovascular disease (ASCVD) at a median follow-up of 2.2 years. This trial included patients with LDL-C≥70mg/dL or non-HDL-C ≥100mg/dL on at least moderate-intensity statins. It is not known what proportion of ASCVD patients would qualify for evolocumab based on FOURIER entry criteria and how eligibility would change if maximal doses of evidence-based lipid lowering therapies were required...
May 2, 2017: Circulation
https://www.readbyqxmd.com/read/28459663/does-evolocumab-as-a-pcsk9-inhibitor-ameliorate-the-lipid-profile-in-familial-hypercholesterolemia-patients-a-meta-analysis-of-randomized-controlled-trials
#14
Seyyed Majid Eslami, Shekoufeh Nikfar, Maryam Ghasemi, Mohammad Abdollahi
Proprotein convertase subtilisin-kexin type 9 (PCSK9) is a member of regulatory serine proteases which is mostly expressed in liver. In the physiological condition, LDL-C binds to LDL receptors (LDLRs) and via endocytosis, LDLRs are degraded. PCSK9 binds to the epidermal growth factor-like repeat A (EGFA) domain of extracellular LDLRs, and then physiological recycling of LDLRs from surface of liver is cancelled, resulting in elevation of circulating LDL-C in plasma. To evaluate whether evolucomab, as PCSK9 inhibitor monoclonal antibody, ameliorates lipid profile in familial hypercholesterolemia (FH) patients, this meta-analysis has been conducted...
2017: Journal of Pharmacy & Pharmaceutical Sciences: a Publication of the Canadian Society for Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28456096/identifying-low-density-lipoprotein-cholesterol-associated-variants-in-the-annexin-a2-anxa2-gene
#15
Roaa Hani Fairoozy, Jackie Cooper, Jon White, Claudia Giambartolomei, Lasse Folkersen, S Goya Wannamethee, Barbara J Jefferis, Peter Whincup, Yoav Ben-Shlomo, Meena Kumari, Mika Kivimaki, Andrew Wong, Rebecca Hardy, Diana Kuh, Tom R Gaunt, J P Casas, Stela McLachlan, Jackie F Price, Aroon Hingorani, Anders Franco-Cereceda, Thomas Grewal, Anastasia Z Kalea, Steve E Humphries
BACKGROUND AND AIMS: Annexin-A2 (AnxA2) is an endogenous inhibitor of proprotein convertase subtilisin/kexin type-9 (PCSK9). The repeat-one (R1) domain of AnxA2 binds to PCSK9, blocking its ability to promote degradation of low-density lipoprotein cholesterol-receptors (LDL-R) and thereby regulate low-density lipoprotein cholesterol (LDL-C) levels. Here we identify variants in ANXA2 influencing LDL-C levels and we determine the molecular mechanisms of their effects. RESULTS: The ANXA2 single nucleotide polymorphism (SNP) genotype-phenotype association was examined using the Second-Northwick-Park Heart Study (NPHSII) (n∼2700) and the UCL-LSHTM-Edinburgh-Bristol (UCLEB) consortium (n∼14,600)...
April 13, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28453187/pcsk9-monoclonal-antibodies-for-the-primary-and-secondary-prevention-of-cardiovascular-disease
#16
REVIEW
Amand F Schmidt, Lucy S Pearce, John T Wilkins, John P Overington, Aroon D Hingorani, Juan P Casas
BACKGROUND: Despite the availability of effective drug therapies that reduce low-density lipoprotein (LDL)-cholesterol (LDL-C), cardiovascular disease (CVD) remains an important cause of mortality and morbidity. Therefore, additional LDL-C reduction may be warranted, especially for patients who are unresponsive to, or unable to take, existing LDL-C-reducing therapies. By inhibiting the proprotein convertase subtilisin/kexin type 9 (PCSK9) enzyme, monoclonal antibodies (PCSK9 inhibitors) may further reduce LDL-C, potentially reducing CVD risk as well...
April 28, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28446516/access-to-non-statin-lipid-lowering-therapies-in-patients-at-high-risk-of-atherosclerotic-cardiovascular-disease
#17
Joshua W Knowles, William B Howard, Lala Karayan, Seth J Baum, Katherine A Wilemon, Christie M Ballantyne, Kelly D Myers
High-intensity statins are recommended for all patients with familial hypercholesterolemia (FH) and non-statin lipid lowering therapies (LLTs) are indicated when there is an inadequate response to statins(1, 2) In the pre-PCSK9 inhibitor (PCSK9i) era only about 40% of FH patients achieved an LDL-C level <100.(3) Partly based on the need for additional therapeutic options in high-risk FH patients, PCSK9 inhibitors were approved for treatment of heterozygous and homozygous FH in 2015. Nevertheless, emerging anecdotal data suggest that access to non-statin LLTs has been a challenge for FH patients though this has not been systematically evaluated...
April 26, 2017: Circulation
https://www.readbyqxmd.com/read/28445176/novel-lipid-modifying-drugs-to-lower-ldl-cholesterol
#18
Arjen J Cupido, Laurens F Reeskamp, John J P Kastelein
PURPOSE OF REVIEW: Statins have long been the cornerstone for the prevention of cardiovascular disease (CVD). However, because of perceived adverse effects and insufficient efficacy in certain groups of patients, considerable interest exists in the search for alternatives to lower LDL-cholesterol (LDL-C), and the recent approvals of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors underlines the success of this quest. Here, we give an updated overview on the most recent developments in the area of LDL-C lowering agents...
April 25, 2017: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/28444187/modelling-the-cost-effectiveness-pcsk9-inhibitors-vs-ezetimibe-through-ldl-c-reductions-in-a-norwegian-setting
#19
Max Korman, Torbjørn Wisløff
Aims: Despite the success of statins, there remains unmet clinical need in cardiovascular disease (CVD) prevention. New proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors reduce low-density lipoprotein cholesterol (LDL-C) by 55-65%. Two PCSK9 inhibitors, evolocumab and alirocumab, were approved for use in Norway but not yet for reimbursement through public national insurance. We aim to explore the cost-effectiveness of these compared to available treatments in a Norwegian setting...
April 21, 2017: European Heart Journal. Cardiovascular Pharmacotherapy
https://www.readbyqxmd.com/read/28439730/physiological-and-therapeutic-regulation-of-pcsk9-activity-in-cardiovascular-disease
#20
REVIEW
Simon Glerup, Rainer Schulz, Ulrich Laufs, Klaus-Dieter Schlüter
Ischemic heart disease is the main cause of death worldwide and is accelerated by increased levels of low-density lipoprotein cholesterol (LDL-C). Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a potent circulating regulator of LDL-C through its ability to induce degradation of the LDL receptor (LDLR) in the lysosome of hepatocytes. Only in the last few years, a number of breakthroughs in the understanding of PCSK9 biology have been reported illustrating how PCSK9 activity is tightly regulated at several levels by factors influencing its transcription, secretion, or by extracellular inactivation and clearance...
May 2017: Basic Research in Cardiology
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