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Ezetimibe

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https://www.readbyqxmd.com/read/29677301/association-between-baseline-ldl-c-level-and-total-and-cardiovascular-mortality-after-ldl-c-lowering-a-systematic-review-and-meta-analysis
#1
Eliano P Navarese, Jennifer G Robinson, Mariusz Kowalewski, Michalina Kolodziejczak, Felicita Andreotti, Kevin Bliden, Udaya Tantry, Jacek Kubica, Paolo Raggi, Paul A Gurbel
Importance: Effects on specific fatal and nonfatal end points appear to vary for low-density lipoprotein cholesterol (LDL-C)-lowering drug trials. Objective: To evaluate whether baseline LDL-C level is associated with total and cardiovascular mortality risk reductions. Data Sourcesand Study Selection: Electronic databases (Cochrane, MEDLINE, EMBASE, TCTMD, ClinicalTrials.gov, major congress proceedings) were searched through February 2, 2018, to identify randomized clinical trials of statins, ezetimibe, and PCSK9-inhibiting monoclonal antibodies...
April 17, 2018: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/29671538/stable-coronary-artery-disease-treatment
#2
Michael M Braun, William A Stevens, Craig H Barstow
Stable coronary artery disease refers to a reversible supply/demand mismatch related to ischemia, a history of myocardial infarction, or the presence of plaque documented by catheterization or computed tomography angiography. Patients are considered stable if they are asymptomatic or their symptoms are controlled by medications or revascularization. Treatment involves risk factor management, antiplatelet therapy, and antianginal medications. Tobacco cessation, exercise, and weight loss are the most important lifestyle modifications...
March 15, 2018: American Family Physician
https://www.readbyqxmd.com/read/29667439/what-is-the-impact-of-the-2017-cochrane-systematic-review-and-meta-analysis-that-evaluated-the-use-of-pcsk9-inhibitors-for-lowering-cardiovascular-disease-and-mortality
#3
Mohamed A Jalloh, Eric J Ip, Shadi Doroudgar
In 2017, Schmidt et al. conducted a Cochrane systematic review and meta-analysis to evaluate the effect of using proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors to reduce low-density-lipoprotein- cholesterol (LDL-C) and cardiovascular disease (CVD). The Cochrane review was a systematic review and meta-analysis of 20 randomized, double-blinded trials that compared the use of PCSK9 inhibitors with statins/ezetimibe, ezetimibe, or placebo for a treatment duration of at least 24 weeks. The use of PCSK9 inhibitors lowered the risk for CVD (OR 0...
April 18, 2018: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/29650402/proprotein-convertase-subtilisin-kexin-type-9-pcsk9-inhibitor-use-in-the-management-of-resistant-hypercholesterolemia-induced-by-mitotane-treatment-for-adrenocortical-cancer
#4
Efthymia D Tsakiridou, Evangelos Liberopoulos, Zoe Giotaki, Stelios Tigas
We report the case of a patient with probable heterozygous familial hypercholesterolemia and mitotane-induced resistant hypercholesterolemia, despite combination therapy with rosuvastatin and ezetimibe. The patient was managed with the addition of evolocumab. Use of a proprotein convertase subtilisin-kexin type 9 inhibitor, should be considered in patients who develop mitotane-related hypercholesterolemia that cannot be managed with conventional lipid-lowering treatment.
March 13, 2018: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/29649788/lc-ms-ms-method-for-the-simultaneous-quantification-of-intestinal-cyp-and-ugt-activity
#5
Diana Busch, Anja Fritz, Lars Ivo Partecke, Claus-Dieter Heidecke, Stefan Oswald
Many orally administered drugs are subject to first-pass metabolism by cytochrome P450 (CYP) enzymes and uridine 5'-diphospho-glucuronosyltransferases (UGT). While their hepatic activity is well characterized, respective information about the intestine are very scare due to limited availability of tissue, very low microsomal protein content and the heterogeneity of the individual segments. As a consequence, determination of enzyme kinetic parameters is challenging. It was therefore the aim of this study to develop a sensitive liquid chromatography tandem mass spectrometry method for the simultaneous quantification of CYP and UGT metabolites formed by clinically relevant intestinal biotransformation enzymes: 4-hydroxydiclofenac (CYP2C9), 5-hydroxyomeprazole (CYP2C19), dextrorphan (CYP2D6), 1-hydroxymidazolam (CYP3A), ezetimibe glucuronide (UGT1A) and naloxone glucuronide (UGT2B7)...
April 5, 2018: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/29629619/on-the-population-pharmacokinetics-and-the-enterohepatic-recirculation-of-total-ezetimibe
#6
K Soulele, V Karalis
1. Ezetimibe is a potent cholesterol absorption inhibitor, with an erratic pharmacokinetic (PK) profile, attributed to an extensive enterohepatic recirculation (EHC). 2. The aim of this study was to develop a population PK model able to adequately characterize the complex distribution processes of total ezetimibe. The analysis was performed on the individual concentration-time data obtained from 28 healthy subjects who participated in a bioequivalence study comparing two oral ezetimibe formulations. The population PK analysis was performed using nonlinear mixed effect modelling, where different EHC models were developed and evaluated for their performance...
April 9, 2018: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/29627994/the-prevalence-low-density-lipoprotein-cholesterol-levels-and-treatment-of-patients-at-very-high-risk-of-cardiovascular-events-in-the-united-kingdom-a-cross-sectional-study
#7
Mark D Danese, Eduard Sidelnikov, Lucie Kutikova
OBJECTIVE: To assess the prevalence of patients at very high risk of cardiovascular (CV) events in the United Kingdom (UK) and evaluate low-density lipoprotein cholesterol (LDL-C) values and treatment patterns in these patients. METHODS: This cross-sectional study used primary care data from UK electronic medical records in the Clinical Practice Research Datalink (CPRD) in 2013. Very high-risk patients were defined per European Society of Cardiology guidelines as those with hyperlipidemia (assessed by co-medication) and documented cardiovascular disease (CVD) or hyperlipidemia and type 2 diabetes (DM2) without CVD (DM2w/oCVD)...
April 9, 2018: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/29609755/bempedoic-acid-etc-1002-a-current-review
#8
REVIEW
Anum Saeed, Christie M Ballantyne
Although statins are first-line therapy for low-density lipoprotein cholesterol (LDL-C) reduction, many individuals on maximally tolerated statin therapy have elevated LDL-C. Bempedoic acid (ETC-1002) is a novel once-daily LDL-C-lowering agent in phase 3 clinical trials. In phase 1 and 2 studies, ETC-1002 was efficacious in lowering LDL-C when used as monotherapy and when added to statin and/or ezetimibe and was well tolerated in patients with statin intolerance. ETC-1002 also improved cardiometabolic risk factors...
May 2018: Cardiology Clinics
https://www.readbyqxmd.com/read/29609751/optimizing-statins-and-ezetimibe-in-guideline-focused-management
#9
REVIEW
Aref A Bin Abdulhak, Jennifer G Robinson
Statins are essential medications in the management of patients with clinical atherosclerotic cardiovascular disease, and have been supported by numerous clinical trials. Emerging evidence suggests that adding ezetimibe to statin therapy is associated with a net benefit and improved hard clinical outcomes, particularly in patients with significantly elevated atherosclerotic cardiovascular disease risk and elevated low-density lipoprotein cholesterol levels.
May 2018: Cardiology Clinics
https://www.readbyqxmd.com/read/29602140/effect-of-simvastatin-and-ezetimibe-on-supar-levels-and-outcomes
#10
Gethin W Hodges, Casper N Bang, Julie L Forman, Michael H Olsen, Kurt Boman, Simon Ray, Y Antero Kesäniemi, Jesper Eugen-Olsen, Anders M Greve, Jørgen L Jeppesen, Kristian Wachtell
BACKGROUND AND AIMS: Soluble urokinase plasminogen activator receptor (suPAR) is an inflammatory marker associated with cardiovascular disease. Statins lower both low-density lipoprotein (LDL)-cholesterol and C-reactive protein (CRP), resulting in improved outcomes. However, whether lipid-lowering therapy also lowers suPAR levels is unknown. METHODS: We investigated whether treatment with Simvastatin 40 mg and Ezetimibe 10 mg lowered plasma suPAR levels in 1838 patients with mild-moderate, asymptomatic aortic stenosis, included in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study, using a pattern mixture model...
March 16, 2018: Atherosclerosis
https://www.readbyqxmd.com/read/29593789/drugs-involved-in-dyslipidemia-and-obesity-treatment-focus-on-adipose-tissue
#11
REVIEW
Sofia Dias, Sílvia Paredes, Laura Ribeiro
Metabolic syndrome can be defined as a state of disturbed metabolic homeostasis characterized by visceral obesity, atherogenic dyslipidemia, arterial hypertension, and insulin resistance. The growing prevalence of metabolic syndrome will certainly contribute to the burden of cardiovascular disease. Obesity and dyslipidemia are main features of metabolic syndrome, and both can present with adipose tissue dysfunction, involved in the pathogenic mechanisms underlying this syndrome. We revised the effects, and underlying mechanisms, of the current approved drugs for dyslipidemia and obesity (fibrates, statins, niacin, resins, ezetimibe, and orlistat; sibutramine; and diethylpropion, phentermine/topiramate, bupropion and naltrexone, and liraglutide) on adipose tissue...
2018: International Journal of Endocrinology
https://www.readbyqxmd.com/read/29578362/molecular-aspects-of-hypercholesterolemia-treatment-current-perspectives-and-hopes
#12
Najmeh Ahangari, Majid Ghayour Mobarhan, Amir Hosein Sahebkar, Alireza Pasdar
BACKGROUND: Hypercholesterolemia is a pathological condition which has been reported in 39% of the worlds' adult population. We aimed to review molecular aspects of current and novel therapeutic approaches based on low-density lipoprotein cholesterol lowering strategies. METHODS: Searching through PubMed and Scopus databases for relative articles using the following keywords have been done: Hypercholesterolemia, Therapy, lipid-lowering drugs, low-density lipoprotein cholesterol...
March 26, 2018: Annals of Medicine
https://www.readbyqxmd.com/read/29571452/lipids-inflammation-and-chronic-kidney-disease-a-sharp-perspective
#13
David D Waters, Liffert Vogt
Accumulating evidence indicates that inflammation plays a role in the initiation and progression of chronic kidney disease. In the Study of Heart and Renal Protection (SHARP) trial, higher baseline C-reactive protein and higher baseline low-density lipoprotein cholesterol levels were both associated with a higher risk of cardiovascular events, but higher baseline C-reactive protein levels were also associated with a higher risk of nonvascular events. Simvastatin/ezetimibe reduced cardiovascular events independent of baseline C-reactive protein levels...
April 2018: Kidney International
https://www.readbyqxmd.com/read/29569492/a-bayesian-network-meta-analysis-of-pcsk9-inhibitors-statins-and-ezetimibe-with-or-without-statins-for-cardiovascular-outcomes
#14
Safi U Khan, Swapna Talluri, Haris Riaz, Hammad Rahman, Fahad Nasir, Irbaz Bin Riaz, Sudhakar Sattur, Haitham Ahmed, Edo Kaluski, Richard Krasuski
Background The comparative effects of statins, ezetimibe with or without statins and proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors remain unassessed. Design Bayesian network meta-analysis was conducted to compare treatment groups. Methods Thirty-nine randomized controlled trials were selected using MEDLINE, EMBASE, and CENTRAL (inception - September 2017). Results In network meta-analysis of 189,116 patients, PCSK9 inhibitors were ranked as the best treatment for prevention of major adverse cardiovascular events (Surface Under Cumulative Ranking Curve (SUCRA), 85%), myocardial infarction (SUCRA, 84%) and stroke (SUCRA, 80%)...
January 1, 2018: European Journal of Preventive Cardiology
https://www.readbyqxmd.com/read/29551054/ezetimibe-decreased-nonalcoholic-fatty-liver-disease-activity-score-but-not-hepatic-steatosis
#15
Hyo Young Lee, Dae Won Jun, Hyun Jung Kim, Hyunwoo Oh, Waqar Khalid Saeed, Hyeongsik Ahn, Ramsey C Cheung, Mindie H Nguyen
Background/Aims: A number of clinical trials reported varying effects of cholesterol lowering agents in nonalcoholic fatty liver disease (NAFLD) patients. We, therefore, assessed the changes in hepatic steatosis and NAFLD activity score (NAS) after treatment with cholesterol lowering agents in NAFLD patients by metaanalysis. Methods: The Cochrane Library, the MEDLINE, and the Embase databases were searched until May 2015, without any language restrictions, for randomized controlled trials (RCTs) and nonrandomized studies (NRSs)...
March 20, 2018: Korean Journal of Internal Medicine
https://www.readbyqxmd.com/read/29548678/prescribing-patterns-of-proprotein-convertase-subtilisin-kexin-type-9-inhibitors-in-eligible-patients-with-clinical-atherosclerotic-cardiovascular-disease-or-heterozygous-familial-hypercholesterolemia
#16
Dean G Karalis, Usha G Mallya, Ameen F Ghannam, Joseph Elassal, Rishab Gupta, Susan H Boklage
Two proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors are approved for patients with atherosclerotic cardiovascular disease or heterozygous familial hypercholesterolemia who require additional low-density lipoprotein cholesterol (LDL-C) lowering. This retrospective study sought to determine differences between eligible patients who were prescribed and those who were not prescribed a PCSK9 inhibitor. Patients from an electronic medical record database were included in the analysis, and their demographic, clinical, and treatment characteristics were evaluated...
February 12, 2018: American Journal of Cardiology
https://www.readbyqxmd.com/read/29544086/new-medications-targeting-triglyceride-rich-lipoproteins-can-inhibition-of-angptl3-or-apoc-iii-reduce-the-residual-cardiovascular-risk
#17
REVIEW
Vesa M Olkkonen, Juha Sinisalo, Matti Jauhiainen
Remarkably good results have been achieved in the treatment of atherosclerotic cardiovascular diseases (CVD) by using statin, ezetimibe, antihypertensive, antithrombotic, and PCSK9 inhibitor therapies and their proper combinations. However, despite this success, the remaining CVD risk is still high. To target this residual risk and to treat patients who are statin-intolerant or have an exceptionally high CVD risk for instance due to familial hypercholesterolemia (FH), new therapies are intensively sought. One pathway of drug development is targeting the circulating triglyceride-rich lipoproteins (TRL) and their lipolytic remnants, which, according to the current view, confer a major CVD risk...
March 8, 2018: Atherosclerosis
https://www.readbyqxmd.com/read/29541476/antidyslipidemic-potential-of-a-novel-farnesoid-x-receptor-antagonist-in-a-hamster-model-of-dyslipidemia-comparative-studies-of-other-nonstatin-agents
#18
Emiko Shinozawa, Yuichiro Amano, Hiroko Yamakawa, Megumi Haba, Mitsuyuki Shimada, Ryuichi Tozawa
We attempted to clarify the therapeutic capability of antagonists of the farnesoid X receptor (FXR), a nuclear receptor that regulates lipid and bile acid metabolism. Herein, we report the antidyslipidemic effects of a novel synthesized FXR antagonist, compound-T1, utilizing a dyslipidemic hamster model. Compound-T1 selectively inhibited chenodeoxycholic acid-induced FXR activation (IC50 , 2.1 nmol·L-1 ). A hamster model of diet-induced hyperlipidemia was prepared to investigate the antidyslipidemic effects of compound-T1 through comparative studies of the nonstatin lipid-modulating agents ezetimibe, cholestyramine, and torcetrapib...
April 2018: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/29526502/efficacy-and-safety-of-lipid-lowering-by-alirocumab-in-chronic-kidney-disease
#19
Peter P Toth, Jamie P Dwyer, Christopher P Cannon, Helen M Colhoun, Daniel J Rader, Ashish Upadhyay, Michael J Louie, Andrew Koren, Alexia Letierce, Jonas Mandel, Maciej Banach
Individuals with chronic kidney disease are at increased risk of premature cardiovascular disease. Among them, many with elevated low-density lipoprotein cholesterol (LDL-C) are unable to achieve optimal LDL-C on statins and require additional lipid-lowering therapy. To study this, we compared the LDL-C-lowering efficacy and safety of alirocumab in individuals with hypercholesterolemia with impaired renal function, defined as eGFR 30-59 ml/min/1.73 m2 , to those without impaired renal function eGFR ≥60 ml/min/1...
March 8, 2018: Kidney International
https://www.readbyqxmd.com/read/29525445/alirocumab-in-high-risk-patients-observations-from-the-open-label-expanded-use-program
#20
Charles J Glueck, Alan Brown, Anne C Goldberg, James M McKenney, Louis Kantaros, John Stewart, Joseph Elassal, Andrew Koren
BACKGROUND: The alirocumab expanded use program provided open-label access to alirocumab before its commercial availability to patients with severe hypercholesterolemia not controlled with maximally tolerated doses of standard-of-care lipid-lowering therapy. OBJECTIVE: To describe the safety and lipid-lowering efficacy of alirocumab in high-risk patients who were likely to be early users of proprotein convertase subtilisin/kexin type 9 inhibitors after approval...
February 7, 2018: Journal of Clinical Lipidology
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