Effectiveness of ezetimibe in clinical practice

Jurado, Javier A.; Seip, Richard L.; Thompson, Paul D.

doi:10.1016/j.amjcard.2003.11.040

Cited by 23 publications

(16 citation statements)

References 6 publications

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“…Ezetimibe works by blocking intestinal uptake of dietary cholesterol and bilederived cholesterol; thus, the drug is expected to reduce circulating cholesterol levels even when there is no cholesterol in the diet. [41][42][43][44] Consistent with this expectation, we found that ezetimibe reduced serum cholesterol levels in mice with no cholesterol in their diet. Unlike statins, which block cholesterol synthesis at an early step in the mevalonate pathway, and thus suppress production of upstream intermediates (including isoprenoids), ezetimibe only blocks cholesterol-uptake and likely has no direct effect on other components of the pathway.…”

Section: Discussionsupporting

confidence: 77%

“…We expected that long-term maintenance on the HFHC diet might raise serum triglycerides; conversely, ezetimibe has been reported to exert a modest reduction of triglyceride levels in humans. 41,42 However, in the present study, the HFHC diet did not result in statistically significant increases in serum triglycerides, nor were triglyceride levels significantly reduced in the ezetimibe cohorts (data not shown). Serological testing (AST, ALP, bilirubin, etc) indicated no liver dysfunction in any mouse (data not shown).…”

Section: Resultscontrasting

confidence: 43%

“…Unlike statins, which block cholesterol synthesis at an early step in the mevalonate pathway, and thus suppress production of upstream intermediates (including isoprenoids), ezetimibe only blocks cholesterol-uptake and likely has no direct effect on other components of the pathway. Ezetimibe has been shown to have a modest effect on reducing triglyceride levels in humans, 41,42 but in our studies in mice we found no reduction of serum triglyceride levels, suggesting that altered triglycerides did not contribute to ezetimibe's effects. Our studies also demonstrate that a combination of a LFNC diet and ezetimibe reduces tumor growth additively.…”

Section: Discussioncontrasting

confidence: 45%

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Ezetimibe Is an Inhibitor of Tumor Angiogenesis

Solomon

Pelton

Boucher

et al. 2009

The American Journal of Pathology

102

108

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Epidemiological and preclinical observations have suggested a role for one or more products of the mevalonate/cholesterol biosynthesis pathway in the progression of prostate cancer. In this study, we used ezetimibe (Zetia), a specific, FDA-approved, cholesterol uptake-blocking drug, in combination with either a hyper-or hypocholesterolemic diet, to show that elevated circulating cholesterol levels promote, whereas a reduction in circulating cholesterol levels retard, the growth of human prostate cancer xenograft tumors in mice. Circulating cholesterol levels also modified tumor angiogenesis; higher cholesterol levels increased microvessel density and other indicators of vascularity. Consistent with these data, the reduction of cholesterol levels also increased the levels of the angiogenesis inhibitor thrombospondin-1 in the xenografts. Our results thus suggest that hypercholesterolemia directly accelerates the growth of prostate carcinomas , and that the pharmacological reduction of serum cholesterol levels may retard prostate cancer growth by inhibiting tumor angiogenesis.

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Section: Discussionsupporting

confidence: 77%

Section: Resultscontrasting

confidence: 43%

Section: Discussioncontrasting

confidence: 45%

See 1 more Smart Citation

Ezetimibe Is an Inhibitor of Tumor Angiogenesis

Solomon

Pelton

Boucher

et al. 2009

The American Journal of Pathology

102

108

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“…In addition, synergism is expected because both of these agents target separate pathways (peroxisome proliferatoractivated receptor-α-mediated gene expression changes for fibrates versus intestinal cholesterol absorption for ezetimibe). In a retrospective clinic-based survey of patients taking lipid-lowering agents, the addition of ezetimibe to on-going fibrate therapy led to an approximate 21% LDL cholesterol reduction, similar to that observed for a statin-ezetimibe combination [22]. No side effects with this combination were reported, but some caution must be expressed until formal prospective studies with much larger numbers have been reported.…”

Section: Clinical Studiesmentioning

confidence: 99%

Ezetimibe: A novel cholesterol-lowering agent that highlights novel physiologic pathways

Patel

2004

Curr Cardiol Rep

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Ezetimibe is a US Food and Drug Administration-approved novel drug that targets the absorption of cholesterol in the intestine. The identification of this drug has also led to the elucidation of the dietary cholesterol receptor. Ezetimibe is efficacious as a plasma cholesterol-lowering agent as monotherapy, but its greatest utility seems to be as a combination with a low-dose statin, where it results in cholesterol lowering that is equivalent to using maximum-dose statins. It has a very favorable sideeffect profile, as well as a lack of drug-drug interactions. In addition, it prevents the absorption of noncholesterol sterols, such as plant sterols. In clinical studies, it has been shown to be highly efficacious in lowering plant sterols in a rare genetic disorder, sitosterolemia. Both the disease, as well as this therapeutic agent, have led to the concept that ezetimibe may be also useful in dissecting the role of these noncholesterol sterols in the pathogenesis of atherosclerosis.

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“…Ezetimibe is an FDA approved drug that blocks cholesterol uptake in the gut, thereby lowering serum cholesterol levels. Ezetimibe is a specific antagonist of NPC1L1, the bona fide gut cholesterol transporter [100][101][102][103] . Ezetimibe has no known target other than NPC1L1, and NPC1L1 is expressed only in the gut, and in hepatocytes (in humans), but not by tumor cells.…”

Section: Cholesterol Tumor Growth and Androgen Synthesis In The Mousementioning

confidence: 99%

Disparities in Intratumoral Steroidogenesis

Solomon¹,

Pelton²

2013

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT NUMBERChildren's Hospital Corporation, The Boston MA 02115-5724 SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR'S ACRONYM(S)U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 SPONSOR/MONITOR'S REPORT NUMBER(S) DISTRIBUTION / AVAILABILITY STATEMENTApproved for Public Release; Distribution Unlimited SUPPLEMENTARY NOTES ABSTRACTProstatic adenocarcinoma (PC) is the most common form of non-cutaneous cancer and second most lethal cancer in American men but demonstrates tremendous disparity in both incidence and severity between African American men (AAM) and Caucasian men (CM). We have identified prostatic intratumoral steroidogenesis as a biological factor that may explain some or much of the disparity in lethal PC rates between AAM and CM. We proposed testing this hypothesis by examining intratumoral steroidogenesis in the prostates of men following radical prostatectomy and in vivo model systems. In this project period we have finished our initial round of in vivo modeling and have demonstrated that hypercholesterolemia contributes to prostate tumor growth in our model mimicking the human patient situation in which androgen deprivation therapy (castration) is applied after tumor initiation. End point testing is currently underway and we anticipate finding excess androgen and nuclear AR in tumors undergoing relapse in hypercholesterolemic mice. Blinded analysis is ongoing and will be unblinded as soon as all end point data has been collected. The final data are anticipated to reveal that, as hypothesized, hypercholesterolemia contributes to faster relapse after castration and increases intratumoral steroidogenesis. SUBJECT TERMS

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Effectiveness of ezetimibe in clinical practice

Cited by 23 publications

References 6 publications

Ezetimibe Is an Inhibitor of Tumor Angiogenesis

Ezetimibe Is an Inhibitor of Tumor Angiogenesis

Ezetimibe: A novel cholesterol-lowering agent that highlights novel physiologic pathways

Disparities in Intratumoral Steroidogenesis

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