title: ApoA-I induction as a potential cardioprotective strategy: rationale for the SUSTAIN and ASSURE studies.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Cleveland Clinic Coordinating Center for Clinical Research, Cleveland, USA. nichols1@ccf.org
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Nicholls
authors.forename: Allan
authors.initials: A
authors.lastname: Gordon
authors.forename: Jan
authors.initials: J
authors.lastname: Johannson
authors.forename: Christie M
authors.initials: CM
authors.lastname: Ballantyne
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Barter
authors.forename: H Bryan
authors.initials: HB
authors.lastname: Brewer
authors.forename: John J P
authors.initials: JJ
authors.lastname: Kastelein
authors.forename: Norman C
authors.initials: NC
authors.lastname: Wong
authors.forename: Marilyn R N
authors.initials: MR
authors.lastname: Borgman
authors.forename: Steven E
authors.initials: SE
authors.lastname: Nissen
mesh_terms: D000293:Adolescent; D016632:Apolipoprotein A-I / Q000096:biosynthesis* / Q000378:metabolism; D002316:Cardiotonic Agents / Q000378:metabolism*; D008076:Cholesterol, HDL / Q000378:metabolism; D017023:Coronary Angiography / Q000379:methods; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging / Q000188:drug therapy*; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D058226:Plaque, Atherosclerotic / Q000188:drug therapy / Q000378:metabolism; D011799:Quinazolines / Q000627:therapeutic use*; D052999:Quinazolinones; D014463:Ultrasonography
chemical_list: D016632:Apolipoprotein A-I; D002316:Cardiotonic Agents; D008076:Cholesterol, HDL; D011799:Quinazolines; D052999:Quinazolinones; C000628794:apabetalone