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Impact of ezetimibe on atherosclerosis: is the jury still out?

ABSTRACT: Ezetimibe is a new lipid-lowering agent that inhibits intestinal absorption of dietary cholesterol. It substantially lowers low-density lipoprotein cholesterol levels when used alone or in combination with statins. However, its effect on cardiovascular mortality remains unknown. We reviewed peer-reviewed published literature on the effect of ezetimibe on different phases of atherosclerosis. MEDLINE, EMBASE, BIOSIS, and other Web of Knowledge databases were searched for relevant abstracts and articles published in the English language that compared ezetimibe and statins as modulators of atherosclerosis. On the basis of the available evidence, ezetimibe appears to reduce inflammation when used in combination with statins, but its effect on endothelial function is mixed and less clear. The effect of ezetimibe on coronary disease progression or prevention of cardiovascular events is currently unknown. Use of ezetimibe as a second- or third-line agent to achieve low-density lipoprotein cholesterol treatment goals seems appropriate on the basis of the available evidence.

SUBMITTER: Al Badarin FJ

PROVIDER: S-EPMC2665981 | biostudies-other | 2009 Apr

REPOSITORIES: biostudies-other

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Impact of ezetimibe on atherosclerosis: is the jury still out?

Al Badarin Firas J FJ Kullo Iftikhar J IJ Kopecky Stephen L SL Thomas Randal J RJ

Mayo Clinic proceedings 20090401 4

Ezetimibe is a new lipid-lowering agent that inhibits intestinal absorption of dietary cholesterol. It substantially lowers low-density lipoprotein cholesterol levels when used alone or in combination with statins. However, its effect on cardiovascular mortality remains unknown. We reviewed peer-reviewed published literature on the effect of ezetimibe on different phases of atherosclerosis. MEDLINE, EMBASE, BIOSIS, and other Web of Knowledge databases were searched for relevant abstracts and art ...[more]

PMID: 19339654

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Project description:Ezetimibe, as a cholesterol absorption inhibitor, has been shown protecting against atherosclerosis when combined with statin. However, side by side comparison has not been made to evaluate the beneficial effects of ezetimibe alone versus statin. Herein, the study aimed to test whether ezetimibe alone would exhibit similar effects as statin and the combination therapy would be necessary in a moderate lesion size.ApoE-/- male mice that were fed a saturated-fat supplemented diet were randomly assigned to different therapeutic regimens: vehicle, ezetimibe alone (10 mg/kg/day), atorvastatin (20 mg/kg/day) or combination of ezetimibe and atorvastatin through the drinking water. On 28 days, mice were sacrificed and aorta and sera were collected to analyze the atherosclerotic lesion and blood lipid and cholesterol levels. As a result, ezetimibe alone exerted similar protective effects on atherosclerotic lesion sizes as atorvastatin, which was mediated by lowering serum cholesterol concentrations, inhibiting macrophage accumulation in the lesions and reducing circulatory inflammatory cytokines, such as monocyte chemoattractant protein (MCP-1) and tumor necrosis factor (TNF-?). In contrast to ezetimibe administration, atorvastatin alone attenuated atherosclerotic lesion which is dependent on its anti-inflammation effects. There were no significance differences in lesion areas and serum concentrations of cholesterol, oxidized LDL and inflammatory cytokines between combination therapy and monotherapy (either ezetimibe or atorvastatin). There were significant correlations between the lesion areas and serum concentrations of cholesterol, MCP-1 and TNF-?, respectively. However, there were no significant correlations between the lesion areas and serum concentrations of TGF-?1 and oxLDL.Ezetimibe alone played the same protection against a moderate atherosclerotic lesion as atorvastatin, which was associated with lowering serum cholesterol, decreasing circulating inflammatory cytokines, and inhibiting macrophage accumulation in the lesions.

Project description:Surgical treatment for epilepsy has made tremendous strides in the past few decades as a result of advances in neurodiagnostics-particularly structural and functional neuroimaging-and improved surgical techniques. This has not only resulted in better outcomes with respect to epileptic seizures and quality of life, and reduced surgical morbidity and mortality, but it has also increased the population of patients now considered as surgical candidates, particularly in the pediatric age range, and enhanced cost-effectiveness sufficient to make surgical treatment available to countries with limited resources. Yet surgical treatment for epilepsy remains arguably the most underutilized of all accepted medical interventions. In the United States, less than 1% of patients with pharmacoresistant epilepsy are referred to epilepsy centers. Although the number of epilepsy surgery centers has increased appreciably over the past two decades, the number of therapeutic surgical procedures performed for epilepsy has not increased at all. For patients who are referred, the average delay from onset of epilepsy to surgery is more than 20 years-too late for many to avoid a lifetime of disability or premature death. Not only has there been no consistent message to convince neurologists and primary care physicians to refer patients for surgery, but the increase in epilepsy surgery centers in the United States has appeared to result in a divergence of approaches to surgical treatment. Efforts are still needed to further improve the safety and efficacy of surgical treatment, including the identification of biomarkers that can reliably determine the extent of the epileptogenic region; however, the greatest benefits would derive from increasing access for potential surgical candidates to epilepsy surgery facilities. Information is needed to determine why appropriate surgical referrals are not being made. Consensus conferences are necessary to resolve controversies that still exist regarding presurgical evaluation and surgical approaches. Standards should be established for certifying epilepsy centers as recommended by the Institute of Medicine's report on epilepsy. Finally, the epilepsy community should not be promoting epilepsy surgery per se but instead emphasize that epilepsy centers do more than epilepsy surgery, promoting the message: All patients with disabling pharmacoresistant seizures deserve evaluation by specialists at epilepsy centers who can provide a variety of advanced diagnostic and therapeutic services.

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Impact of ezetimibe on atherosclerosis: is the jury still out?

Publications

Impact of ezetimibe on atherosclerosis: is the jury still out?

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