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.

Junya Ako, Kiyoshi Hibi, Ken Kozuma, Katsumi Miyauchi, Yoshihiro Morino, Toshiro Shinke, Kenichi Tsujita, Kiyoko Uno, Yumiko Kawabata, Takafumi Hiro

Journal: Journal of cardiology 2019;71(6):583-589

PMID: 29606415

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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.

Address: Department of Cardiovascular Medicine, Kitasato University Hospital, Sagamihara-City, Kanagawa, Japan. Electronic address: [email protected].; Division of Cardiology, Yokohama City University Medical Center, Yokohama-City, Kanagawa, Japan.; Division of Cardiology, Teikyo University Hospital, Itabashi-ku, Tokyo, Japan.; Division of Cardiovascular Medicine, Department of Internal Medicine, Juntendo University Hospital, Bunkyo-ku, Tokyo, Japan.; Division of Cardiology, Department of Internal Medicine, Iwate Medical University, Morioka-city, Iwate, Japan.; Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe-city, Hyogo, Japan.; Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto-City, Kumamoto, Japan.; Cardiovascular Medical, Sanofi, Shinjuku-ku, Tokyo, Japan.; Clinical Sciences and Operations, R&D, Sanofi, Shinjuku-ku, Tokyo, Japan.; Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Itabashi-ku, Tokyo, Japan.

DOI: 10.1016/j.jjcc.2017.11.013