In Japanese patients with familial hypercholesterolaemia, anacetrapib cuts LDL-C by nearly 30% versus placebo in 12 weeks (Atherosclerosis 2016)

Original title: Efficacy and safety of the cholesteryl ester transfer protein inhibitor anacetrapib in Japanese patients with heterozygous familial hypercholesterolemia

Atherosclerosis · 25 March 2016 · 6

Arai H, Teramoto T, Daida H, Ikewaki K, Maeda Y, Nakagomi M, Shirakawa M, Kakikawa T, Numaguchi H, Johnson-Levonas AO, Vaidya S, Blaustein RO

Japanese patients aged 18-80 with genotype-confirmed or clinically diagnosed heterozygous familial hypercholesterolaemia, on stable statin therapy with or without other lipid-modifying agents for at least 6 weeks and LDL-C of at least 100 mg/dL, were randomized to anacetrapib 100 mg (n equals 34) or placebo (n equals 34) for 12 weeks, followed by a 12-week off-drug reversal phase (NCT01824238). At week 12, anacetrapib reduced LDL-C by a between-group difference of 29.8% versus placebo (95% CI -38.6 to -21.0, P less than 0.001), and also reduced non-HDL-C (23. 6%), apoB (14.1%), and Lp(a) (48.7%) while raising HDL-C (110.0%) and apoA1 (48.2%), all P less than 0.001. Anacetrapib was generally well tolerated over 12 weeks, with no between-group differences in drug discontinuation for adverse events or in liver enzyme, creatine kinase, blood pressure, electrolyte, or cardiovascular-event abnormalities.

Original abstract

Background And Aims: This multicenter, randomized, double-blind, placebo-controlled study assessed the lipid-modifying efficacy/safety profile of anacetrapib 100 mg added to ongoing statin ± other lipid-modifying therapies (LMT) in Japanese patients with heterozygous familial hypercholesterolemia (HeFH).

Methods: Patients 18-80 years with a genotype-confirmed/clinical diagnosis of HeFH who were on a stable dose of statin ± other LMT for ≥6 weeks and with an LDL-C concentration ≥100 mg/dL were randomized to anacetrapib 100 mg (n = 34) or placebo (n = 34) for 12 weeks, followed by a 12-week off-drug reversal phase. The primary endpoints were percent change from baseline in LDL-C (beta-quantification method [BQ]) and safety/tolerability.

Results: At Week 12, treatment with anacetrapib reduced LDL-C (BQ) compared to placebo and resulting in a between-group difference of 29.8% (95% CI: -38.6 to -21.0; p < 0.001) favoring anacetrapib. Anacetrapib also reduced non-HDL-C (23. 6%; p < 0.001), ApoB (14.1%; p < 0.001) and Lp(a) (48.7%; p < 0.001), and increased HDL-C (110.0%; p < 0.001) and ApoA1 (48.2%; p < 0.001) versus placebo. Anacetrapib 100 mg added to ongoing therapy with statin ± other LMT for 12 weeks was generally well-tolerated. There were no differences between the groups in the proportion of patients who discontinued drug due to an adverse event or abnormalities in liver enzymes, creatinine kinase, blood pressure, electrolytes or adjudicated cardiovascular events.

Conclusions: In Japanese patients with HeFH, treatment with anacetrapib 100 mg for 12 weeks resulted in substantial reductions in LDL-C and increases in HDL-C and was well tolerated. (ClinicalTrials.govNCT01824238).

Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.