BACKGROUND The ODYSSEY Japan study was designed to demonstrate the reduction in low-density lipoprotein cholesterol (LDL-C) by alirocumab as add-on to existing lipid-lowering therapy in Japanese patients with heterozygous familial hypercholesterolemia (heFH) or non-FH at high cardiovascular risk who require additional pharmacological management to achieve their LDL-C treatment goal (<2.6 or <3.1 mmol/L, depending on risk category). METHODSANDRESULTS This randomized, double-blind, parallel-group, 52-week study was conducted in Japan. Patients (n=216) with heFH, non-FH at high cardiovascular risk with coronary disease, or classified as category III were enrolled. The prespecified safety analysis was done after the last patient completed 52 weeks. Patients were randomized (2:1, alirocumab:placebo) with stratification for heFH to s.c. alirocumab (75 mg every 2 weeks [Q2 W] with increase to 150 mg if week 8 LDL-C ≥2.6/3.1 mmol/L) or placebo for 52 weeks plus stable statin therapy. At week 24, mean±SE change in LDL-C from baseline was -62.5±1.3% in the alirocumab group and 1.6±1.8% in the placebo group (difference, -64.1±2.2%; P<0.0001); the reduction was sustained to week 52 (alirocumab, -62.5±1.4%; placebo, -3.6±1.9%). No patterns were evident between treatment groups for adverse events at 52 weeks. CONCLUSIONS In high-risk Japanese patients with hypercholesterolemia on stable statin therapy, alirocumab markedly reduced LDL-C vs. placebo and was well tolerated over 52 weeks. (Circ J 2016; 80: 1980-1987).