Cardiovascular Drugs and Therapy

, Volume 26, Issue 2, pp 181–187

ApoA-I Induction as a Potential Cardioprotective Strategy: Rationale for the SUSTAIN and ASSURE Studies

  • Stephen J. Nicholls
  • Allan Gordon
  • Jan Johannson
  • Christie M. Ballantyne
  • Philip J. Barter
  • H. Bryan Brewer
  • John J. P. Kastelein
  • Norman C. Wong
  • Marilyn R. N. Borgman
  • Steven E. Nissen
Article

DOI: 10.1007/s10557-012-6373-5

Cite this article as:
Nicholls, S.J., Gordon, A., Johannson, J. et al. Cardiovasc Drugs Ther (2012) 26: 181. doi:10.1007/s10557-012-6373-5

Abstract

Background

Considerable interest has focused on the development of therapies that target the functionality of high-density lipoproteins (HDL). Upregulation of endogenous synthesis of the major protein on HDL particles, apolipoprotein A-I (apoA-I), represents a novel approach to generation of new HDL particles. The Study of Quantitative Serial Trends in Lipids with Apolipoprotein A-I Stimulation (SUSTAIN, NCT01423188) study aims to evaluate the lipid efficacy, safety and tolerability of an apoA-I inducer (RVX-208). The ApoA-I Synthesis Stimulation and Intravascular Ultrasound for Coronary Atheroma Regression Evaluation (ASSURE, NCT01067820) study aims to evaluate the effect of RVX-208 on plaque burden.

Methods

In SUSTAIN, 172 patients with low levels of HDL-C will be randomized to receive RVX-208 100 mg bid or placebo for 24 weeks. The primary efficacy parameter will be the percentage change in HDL-C levels. In ASSURE, 310 patients with angiographic coronary artery disease and low HDL-C levels will be randomized to receive RVX-208 100 mg bid or placebo for 26 weeks. The primary efficacy parameter will be the nominal change in percent atheroma volume (PAV), determined by analysis of intravascular ultrasound (IVUS) images of matched coronary artery segments acquired at baseline and at 26-week follow-up. The effect of RVX-208 on other lipid and inflammatory markers, safety and tolerability will also be assessed in both studies.

Conclusion

ApoA-I induction represents a potential novel strategy to reduce cardiovascular risk, by generating nascent HDL particles. These studies will provide early evaluation of the effects of RVX-208 on lipids and atherosclerotic plaque.

Key words

Atherosclerosis Risk factors ApoA-I High-density lipoproteins Coronary heart disease 

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Stephen J. Nicholls
    • 1
    • 7
  • Allan Gordon
    • 2
  • Jan Johannson
    • 2
  • Christie M. Ballantyne
    • 3
  • Philip J. Barter
    • 4
  • H. Bryan Brewer
    • 5
  • John J. P. Kastelein
    • 6
  • Norman C. Wong
    • 2
  • Marilyn R. N. Borgman
    • 1
  • Steven E. Nissen
    • 1
  1. 1.Cleveland Clinic Coordinating Center for Clinical ResearchClevelandUSA
  2. 2.Resverlogix CorporationCalgaryCanada
  3. 3.Baylor Medical CenterHoustonUSA
  4. 4.Heart Research InstituteSydneyAustralia
  5. 5.Medstar Research InstituteWashington DCUSA
  6. 6.Academic Medical CenterAmsterdamthe Netherlands
  7. 7.Department of Cardiovascular MedicineMail Code JJ-65ClevelandUSA

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