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

Abstract

BackgroundSerial 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. MethodsODYSSEY 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. ConclusionODYSSEY 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.