Effect of alirocumab on coronary atheroma volume in Japanese patients with acute coronary syndromes and hypercholesterolemia not adequately controlled with statins: ODYSSEY J-IVUS rationale and design

J Cardiol. 2018 Jun;71(6):583-589. doi: 10.1016/j.jjcc.2017.11.013. Epub 2018 Mar 30.

Abstract

Background: Serial intravascular ultrasound (IVUS) imaging can be used to evaluate the effect of cholesterol-lowering on coronary atheroma progression and plaque volume, with evidence of potential incremental effects with more aggressive lipid-lowering treatments. Alirocumab is a highly specific, fully human monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9). This study will investigate the effect of alirocumab on coronary artery plaque volume in Japanese patients with a recent acute coronary syndrome (ACS) and hypercholesterolemia while on stable statin therapy.

Methods: ODYSSEY J-IVUS is a phase IV, open-label, randomized, blinded IVUS analysis, parallel-group, multicenter study in Japanese adults recently hospitalized for an ACS and who have elevated low-density lipoprotein cholesterol (LDL-C) values [≥100mg/dL (2.6mmol/L)] at ACS diagnosis and suboptimal LDL-C control on stable statin therapy. Patients will be randomized (1:1) to receive alirocumab or standard-of-care (SOC). The alirocumab arm will receive alirocumab 75mg every 2 weeks (Q2W) added to statin therapy (atorvastatin ≥10mg/day or rosuvastatin ≥5mg/day), with a dose increase to 150mg Q2W in patients whose LDL-C value remains ≥100mg/dL at week 12. The SOC arm will receive atorvastatin ≥10mg/day or rosuvastatin ≥5mg/day, with dose adjustment to achieve LDL-C <100mg/dL. Post-treatment IVUS imaging will be done at week 36±2. The primary objective is to compare the effect of alirocumab versus SOC on coronary atheroma progression (percent change in normalized total atheroma volume) after 9 months of treatment.

Conclusion: ODYSSEY J-IVUS will provide insights into the effect of alirocumab on coronary atherosclerotic plaque volume in patients with a recent ACS and hypercholesterolemia while on stable statin therapy. ClinicalTrials.gov number: NCT02984982.

Keywords: Alirocumab; Coronary artery disease; Low-density lipoprotein cholesterol; Monoclonal antibody.

Publication types

  • Clinical Trial Protocol
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Coronary Syndrome / drug therapy*
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Clinical Trials, Phase IV as Topic
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Hypercholesterolemia / drug therapy*
  • Multicenter Studies as Topic
  • Plaque, Atherosclerotic / drug therapy*
  • Proprotein Convertase 9 / antagonists & inhibitors*
  • Randomized Controlled Trials as Topic

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • PCSK9 protein, human
  • Proprotein Convertase 9
  • alirocumab

Associated data

  • ClinicalTrials.gov/NCT02984982