Role of Ezetimibe in Lipid-Lowering and Cardiovascular Disease Prevention

Abstract With the goal of decreasing low-density cholesterol (LDL-C) to mitigate risk of both primary and secondary cardiovascular outcomes, statins have been the cornerstone of therapy, significantly reducing the incidence of coronary atherosclerotic vascular disease. Previous studies suggest that adding other non-statin LDL-lowering agents may further lower LDL-C without negative side effects. Recent guidelines support the hypothesis that driving the LDL-C level below previously recommended targets may have a beneficial effect. Ezetimibe, a cholesterol absorption blocker that inhibits the Niemann-Pick C1-Like 1 (NPC1L1) receptor, has been the focus of recent trials that support its use in cardiovascular risk reduction. For patients not at goal on statin therapy alone, ezetimibe has proven to be a safe, well-tolerated medication that may be used as an adjunct to statin therapy to further reduce LDL-C, resulting in a significant mortality benefit.
Source: Current Atherosclerosis Reports - Category: Cardiology Source Type: research

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Publication date: 24–30 August 2019Source: The Lancet, Volume 394, Issue 10199Author(s): Kausik K Ray, Pablo Corral, Enrique Morales, Stephen J NichollsSummaryAtherosclerosis and its clinical manifestation as ischaemic heart disease remains a considerable health burden. Given that many factors contribute to ischaemic heart disease, a multifactorial approach to prevention is recommended, starting with lifestyle advice, smoking cessation, and control of known cardiovascular risk factors, such as blood pressure and lipids. Within the lipid profile, the principal target is lowering LDL cholesterol, firstly with lifestyle...
Source: The Lancet - Category: General Medicine Source Type: research
Publication date: Available online 1 May 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of LipidsAuthor(s): Ruoqi Li, Yi Liu, Jingjing Shi, Yantong Yu, Haifei Lu, Lu Yu, Yanqiang Liu, Fengxia ZhangAbstractHypercholesterolemia is a preventable risk factor for atherosclerosis and cardiovascular disease. However, the mechanisms of diosgenin (DG) that promote cholesterol homeostasis and alleviate hypercholesterolemia remain elusive. To investigate the effects and molecular mechanisms of the promotion of cholesterol metabolism by DG, a rat model of hypercholesterolemia was induced by providing a hi...
Source: Biochimica et Biophysica Acta (BBA) Molecular and Cell Biology of Lipids - Category: Lipidology Source Type: research
Abstract Niemann Pick C (NPC) is a fatal hereditary neurovisceral disorder associated with a progressive loss of neurons of unknown mechanism. The disease is caused by mutation in either of two genes, termed npc1 and npc2, accounting for ∼95% and ∼5% of patients, respectively. Recent data suggest a cell-autonomous cause for neuronal cell death. In a former study we could demonstrate that cultured NPC1-deficient (NPC1-/-) neurons are more susceptible to autophagic stress than NPC1-wildtype (wt) neurons. In the present study we tested other stressors for a selective effect on the survival of NPC1-/- neurons....
Source: Neuropharmacology - Category: Drugs & Pharmacology Authors: Tags: Neuropharmacology Source Type: research
This study was designed to investigate the pleiotropic actions of simvastatin, one of the most commonly prescribed statins, on macrophage cholesterol homeostasis with a focus on lysosomal free cholesterol egression. With simultaneous nile red and filipin staining, analysis of confocal/multi-photon imaging demonstrated that simvastatin markedly attenuated unesterified (free) cholesterol buildup in macrophages loaded with oxidized low-density lipoprotein but had little effect in reducing the sizes of cholesteryl ester-containing lipid droplets; the reduction in free cholesterol was mainly attributed to decreases in lysosome-...
Source: J Cell Mol Med - Category: Molecular Biology Authors: Tags: J Cell Mol Med Source Type: research
We present an up-to-date overview of the use of human genetics to predict effects and adverse effects of lipid-targeting drugs. Recent findings: LDL cholesterol lowering variants in HMG-Coenzyme A reductase and Niemann-Pick C1-like protein 1, the targets for statins and ezetimibe, protect against ischemic heart disease (IHD). However, HMG-Coenzyme A reductase and Niemann-Pick C1-Like Protein 1-variants also increase the risk of type 2 diabetes and gallstone disease, respectively. Mutations in proprotein convertase subtilisin kexin 9 (PCSK9), apolipoprotein B, and microsomal triglyceride transfer protein cause low LDL chol...
Source: Current Opinion in Lipidology - Category: Lipidology Tags: GENETICS AND MOLECULAR BIOLOGY: Edited by Robert A. Hegele Source Type: research
Abstract Circulating levels of cholesterol derive from either endogenous production or intestinal absorption of dietary and biliary cholesterol. Niemann-Pick C1-Like 1 (NPC1L1) is a transmembrane protein that plays a key role in the intestinal absorption of cholesterol by facilitating its uptake through vesicular endocytosis. NPC1L1 is the molecular target of ezetimibe which binds its extracellular loop and inhibits sterol absorption without affecting the absorption of other molecules. Ezetimibe significantly reduces plasma levels of total and low density lipoprotein cholesterol (LDL-C) as monotherapy or when adde...
Source: Current Medicinal Chemistry - Category: Chemistry Authors: Tags: Curr Med Chem Source Type: research
Please wait while the activity loads. If this activity does not load, try refreshing your browser. Also, this page requires javascript. Please visit using a browser with javascript enabled. If loading fails, click here to try again Click on the 'Start' button to begin the mock test. After answering all questions, click on the 'Get Results' button to display your score and the explanations. There is no time limit for this mock test. Start Congratulations - you have completed DM / DNB Cardiology Entrance Mock Test 15. You scored %%SCORE%% out of %%TOTAL%%. Your performance has been rat...
Source: Cardiophile MD - Category: Cardiology Authors: Tags: Cardiology MCQ DM / DNB Cardiology Entrance Featured Source Type: blogs
CONCLUSION: PR but not EZ treatment reduced duodenal cholesterol transporter expression in mice. PR-induced increases in LXRa  mRNA levels may be involved in attenuation of NPC1L1 expression, subsequently decreasing intestinal cholesterol absorption. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page. PMID: 26670369 [PubMed - as supplied by publisher]
Source: J Pharm Pharm Sci - Category: Drugs & Pharmacology Authors: Tags: J Pharm Pharm Sci Source Type: research
Commentary on: Cannon CP, Blazing MA, Giugliano RP, et al., IMPROVE-IT Investigators. Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes. N Engl J Med 2015;372:2387–97. Context Use of statin therapy to treat dyslipidemia in patients with established coronary artery disease is the standard of care worldwide. Given the negative results of a number of trials that tested the use of adjuvant lipid-lowering therapies against a statin background, there has been great scepticism about whether or not non-statin drugs provide incremental benefit.1–3 Ezetimibe inhibits the absorption of both dietary and bili...
Source: Evidence-Based Medicine - Category: Internal Medicine Authors: Tags: Health policy, Epidemiologic studies, Genetics, Immunology (including allergy), Vaccination / immunisation, Stroke, Diet, Ischaemic heart disease, Health economics, Health service research, Lipid disorders Therapeutics/Prevention Source Type: research
Authors: Madra M, Sturley SL Abstract The isolation of the causative genes for Niemann-Pick type C disease, a panethnic lysosomal lipid storage disorder, has provided models of how sterols and other lipids such as glycosphingolipids traverse the membranes of eukaryotic cells. Unfortunately, these molecular advances have yet to reciprocate with a cure for this devastating neurodegenerative disorder where neuronal replenishment will most likely yield the greatest benefit. In the meantime, stabilizing treatment strategies based on the removal of presumably toxic metabolites are in place. For example, the small molecul...
Source: Clinical Lipidology - Category: Lipidology Tags: Clin Lipidol Source Type: research
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