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https://www.readbyqxmd.com/read/28529918/advances-in-dyslipidemia-management-for-prevention-of-atherosclerosis-pcsk9-monoclonal-antibody-therapy-and-beyond
#1
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/28505047/advances-in-the-management-of-dyslipidemia
#2
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/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/28488460/the-efficacy-of-evolocumab-in-the-management-of-hyperlipidemia-a-systematic-review
#4
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/28465286/estimation-of-eligibility-for-pcsk9-inhibitors-and-associated-costs-based-on-the-fourier-trial-insights-from-the-department-of-veterans-affairs
#5
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
#6
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/28453187/pcsk9-monoclonal-antibodies-for-the-primary-and-secondary-prevention-of-cardiovascular-disease
#7
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/28449836/aortic-calcification-progression-in-heterozygote-familial-hypercholesterolemia
#8
Manal Al Kindi, Alexandre M Bélanger, Karl Sayegh, Soumia Senouci, Sumayah Aljenedil, Lojan Sivakumaran, Isabelle Ruel, Khalid Al Rasadi, Khalid Al Waili, Zuhier Awan, David Valenti, Jacques Genest
BACKGROUND: Patients with homozygous and heterozygous familial hypercholesterolemia (HeFH) develop severe aortic calcifications in an age- and gene dosage-dependent manner. The purpose of this study was to determine the rate of progression of aortic calcification in patients with HeFH. METHODS: We performed thoracoabdominal computed tomography scans and quantified aortic calcium (AoCa) score in 16 HeFH patients, all with the null low-density lipoprotein (LDL) receptor DEL15Kb mutation...
May 2017: Canadian Journal of Cardiology
https://www.readbyqxmd.com/read/28444274/evolocumab-added-to-statins-to-reduce-progression-of-coronary-atherosclerosis-reply
#9
LETTER
Stephen J Nicholls, Ransi Somaratne, Steven E Nissen
No abstract text is available yet for this article.
April 25, 2017: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/28444271/evolocumab-added-to-statins-to-reduce-progression-of-coronary-atherosclerosis
#10
LETTER
Mohammad Alkhalil, Robin P Choudhury
No abstract text is available yet for this article.
April 25, 2017: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/28444270/evolocumab-added-to-statins-to-reduce-progression-of-coronary-atherosclerosis
#11
LETTER
Scott W Murray
No abstract text is available yet for this article.
April 25, 2017: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/28444187/modelling-the-cost-effectiveness-pcsk9-inhibitors-vs-ezetimibe-through-ldl-c-reductions-in-a-norwegian-setting
#12
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
#13
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
https://www.readbyqxmd.com/read/28424973/pcsk9-inhibitors-in-hyperlipidemia-current-status-and-clinical-outlook
#14
Belinda Di Bartolo, Daniel J Scherer, Alex Brown, Peter J Psaltis, Stephen J Nicholls
The clinical reality of residual risk despite statin (HMG-CoA reductase inhibitor) therapy and emergence of statin intolerance support the need to develop additional lipid-lowering strategies. Proprotein convertase subtilisin kexin type 9 (PCSK9) has received considerable attention by virtue of genetic and clinical studies that have revealed its pivotal role in the regulation of cholesterol homeostasis. Monoclonal antibodies have been developed targeting PCSK9, which have been demonstrated to produce profound low-density lipoprotein cholesterol (LDL-C) lowering when provided as monotherapy or in combination with statins...
April 19, 2017: BioDrugs: Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy
https://www.readbyqxmd.com/read/28419071/reduction-of-cardiovascular-risk-with-evolocumab-repatha
#15
(no author information available yet)
No abstract text is available yet for this article.
April 24, 2017: Medical Letter on Drugs and Therapeutics
https://www.readbyqxmd.com/read/28367845/one-year-efficacy-and-safety-of-evolocumab-in-japanese-patients%C3%A3-a-pooled-analysis-from-the-open-label-extension-osler-studies
#16
Atsushi Hirayama, Shizuya Yamashita, Hyoe Inomata, Helina Kassahun, Marcoli Cyrille, Andrea Ruzza, Masayuki Yoshida, Arihiro Kiyosue, Yuhui Ma, Tamio Teramoto
BACKGROUND: Evolocumab, a fully human monoclonal antibody against PCSK9, significantly reduced low-density lipoprotein-cholesterol (LDL-C) levels in Japanese patients by up to 76% when administered with a statin. We evaluated the efficacy and safety of 1 year of evolocumab in a pooled analysis of patients from the 12-week YUKAWA studies who continued into the open-label extension (OLE) OSLER studies.Methods and Results:YUKAWA-1 and YUKAWA-2 were conducted in hypercholesterolemic, high-cardiovascular-risk Japanese patients who were receiving statin therapy...
March 29, 2017: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/28366593/cost-effectiveness-of-evolocumab-in-patients-with-high-cardiovascular-risk-in-spain
#17
Guillermo Villa, Mickael Lothgren, Lucie Kutikova, Peter Lindgren, Shravanthi R Gandra, Gregg C Fonarow, Francesc Sorio, Lluis Masana, Antoni Bayes-Genis, Ben van Hout
PURPOSE: Our objective was to assess the cost-effectiveness of evolocumab in patients at high risk of cardiovascular (CV) events from the Spanish National Health System perspective. METHODS: A Markov model was used to assess the cost-effectiveness (incremental [∆] cost per ∆ quality-adjusted life-year [QALY]; or cost utility) of evolocumab plus standard of care (SoC; statins) versus SoC, assuming lifetime treatment. Cohorts with baseline LDL-C >100 mg/dL and familial hypercholesterolemia (FH) or CV event history (secondary prevention [SP]) were considered...
March 30, 2017: Clinical Therapeutics
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
#18
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/28328015/pcsk9-inhibitor-access-barriers-issues-and-recommendations-improving-the-access-process-for-patients-clinicians-and-payers
#19
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...
April 2017: Clinical Cardiology
https://www.readbyqxmd.com/read/28320695/evolocumab-reduces-cardiovascular-events-in-patients-with-heart-disease-finds-study
#20
Susan Mayor
No abstract text is available yet for this article.
March 19, 2017: BMJ: British Medical Journal
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