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Cited by 220Lipoproteins and Cardiovascular HealthCholesterol and Lipid MetabolismLipid metabolism and disorders

The DOI matches its Crossref record; 30 of the 31 references it cites were found in a registry or an index.

Inhibition of microsomal triglyceride transfer protein alone or with ezetimibe in patients with moderate hypercholesterolemia

Samaha, Frederick F, McKenney, James, Bloedon, LeAnne T, Sasiela, William J, Rader, Daniel J·2008·Nature Clinical Practice Cardiovascular Medicine
DOI 10.1038/ncpcardio1250
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Abstract

Background Many patients with coronary heart disease do not achieve recommended LDL-cholesterol levels, due to either intolerance or inadequate response to available lipid-lowering therapy. Microsomal triglyceride transfer protein (MTP) inhibitors might provide an alternative way to lower LDL-cholesterol levels. We tested the safety and LDL-cholesterol-lowering efficacy of an MTP inhibitor, AEGR-733 (Aegerion Pharmaceuticals Inc., Bridgewater, NJ), alone and in combination with ezetimibe.Methods We performed a multicenter, double-blind, 12-week trial, which included 84 patients with hypercholesterolemia. Patients were randomly assigned ezetimibe 10 mg daily (n = 29); AEGR-733 5.0 mg daily for the first 4 weeks, 7.5 mg daily for the second 4 weeks and 10 mg daily for the last 4 weeks (n = 28); or ezetimibe 10 mg daily and AEGR-733 administered with the dose titration described above (n = 28).Results Ezetimibe monotherapy led to a 20-22% decrease in LDL-cholesterol concentrations. AEGR-733 monotherapy led to a dose-dependent decrease in LDL-cholesterol concentration: 19% at 5.0 mg, 26% at 7.5 mg and 30% at 10 mg. Combined therapy produced similar but larger dose-dependent decreases (35%, 38% and 46%, respectively). The number of patients who discontinued study drugs owing to adverse events was five with ezetimibe alone, nine with AEGR-733 alone, and four with combined ezetimibe and AEGR-733. Discontinuations from AEGR-733 were due primarily to mild transaminase elevations.Conclusions Inhibition of LDL production with low-dose AEGR-733, either alone or in combination with ezetimibe, could be an effective therapeutic option for patients unable to reach target LDL-cholesterol levels.

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  1. Zaiss S et al. (1999) BAY 13-9952, an inhibitor of the microsomal triglyceride transfer protein (MTP), inhibits atherosclerotic plaque formation in cholesterol-fed rabbits in spite of a concomitant reductio of vitamin E [Abstr]. Circulation. 100 (Suppl 1): 258

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Metadata

Authors
Samaha, F. F., McKenney, J., Bloedon, L. T., Sasiela, W. J., & Rader, D. J.
Affiliations
  • Philadelphia VA Medical Center (US)
  • Virginia Commonwealth University (US)
  • University of Pennsylvania (US)
  • Aegerion Pharmaceuticals (United States) (US)
Corresponding author
Samaha, Frederick F
ORCID
Venue
Nature Clinical Practice Cardiovascular Medicine
Publisher
Springer Science and Business Media LLC
Published
2008-05-27
Volume
5
Issue
8
Pages
497-505
ISSN
  • 1743-4297 (ISSN-L)
  • 1743-4300
DOI
10.1038/ncpcardio1250
OpenAlex
W2046959088
Cited by
220
References
31
Citations by year
2026: 2 · 2025: 8 · 2024: 11 · 2023: 4 · 2022: 11 · 2021: 5 · 2020: 4 · 2019: 7 · 2018: 10 · 2017: 8 · 2016: 15 · 2015: 18 · 2014: 29 · 2013: 27 · 2012: 23
FWCI
13.35
Type
journal article
Language
en
Open access
closed
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature Clinical Practice Cardiovascular Medicine (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
Keywords
microsomal triglyceride transfer protein, MTP inhibitors, ezetimibe, hypercholesterolemia, LDL cholesterol lowering, combination lipid-lowering therapy, dose titration, transaminase elevation, drug safety, coronary artery disease, statin intolerance, treatment response variability, triglyceride-rich lipoproteins
MeSH terms
Ezetimibe, Aged, Anticholesteremic Agents, Azetidines, Benzimidazoles, Carrier Proteins, Double-Blind Method, Drug Therapy, Combination, Female, Humans, Hypercholesterolemia, Cholesterol, LDL, Male, Microsomes, Middle Aged, Severity of Illness Index, Treatment Outcome

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