Inhibition of microsomal triglyceride transfer protein alone or with ezetimibe in patients with moderate hypercholesterolemia (original) (raw)

Nature Clinical Practice Cardiovascular Medicine volume 5, pages 497–505 (2008)Cite this article

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.

Key Points

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Authors and Affiliations

  1. Division of Cardiovascular Medicine, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
    Frederick F Samaha
  2. Philadelphia Veterans Affairs Medical Center, Philadelphia, PA, USA
    Frederick F Samaha
  3. School of Pharmacy, Virginia Commonwealth University, Richmond, VA, USA
    James McKenney
  4. Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
    LeAnne T Bloedon & Daniel J Rader
  5. Aegerion Pharmaceuticals, Bridgewater, NJ, USA
    William J Sasiela

Authors

  1. Frederick F Samaha
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  2. James McKenney
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  3. LeAnne T Bloedon
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  4. William J Sasiela
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  5. Daniel J Rader
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Corresponding author

Correspondence toFrederick F Samaha.

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Competing interests

This study was funded by Aegerion Inc.

FF Samaha Samaha is funded by Abbott laboratories, Aegerion Inc., and Merck Inc.

J McKenney provides consulting services for Abbott Laboratories, Aegerion Inc., AstraZeneca, Daiichi Sankyo and Merck Inc.

WJ Sasiela is an employee of Aegerion Inc.

DJ Rader is a stockholder and member of the scientific advisory board in Aegerion Inc.

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Samaha, F., McKenney, J., Bloedon, L. et al. Inhibition of microsomal triglyceride transfer protein alone or with ezetimibe in patients with moderate hypercholesterolemia.Nat Rev Cardiol 5, 497–505 (2008). https://doi.org/10.1038/ncpcardio1250

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