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

Autor: Mariko Nakagomi, Hidenori Arai, Hiroyuki Daida, Masayoshi Shirakawa, Hirotaka Numaguchi, Sanskruti Vaidya, Taro Kakikawa, Yuko Maeda, Amy O. Johnson-Levonas, Tamio Teramoto, Katsunori Ikewaki, Robert O. Blaustein
Rok vydání: 2016
Předmět:
Adult
Male
medicine.medical_specialty
Time Factors
Adolescent
Low density lipoprotein cholesterol
Familial hypercholesterolemia
030204 cardiovascular system & hematology
Pharmacology
Placebo
Gastroenterology
Hyperlipoproteinemia Type II
Young Adult
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Double-Blind Method
Japan
Anacetrapib
Internal medicine
Cholesterylester transfer protein
medicine
Humans
030212 general & internal medicine
Oxazolidinones
Aged
Aged
80 and over
biology
business.industry
Cholesterol
HDL
Homozygote
Cholesterol
LDL
Middle Aged
medicine.disease
Cholesterol Ester Transfer Proteins
Safety profile
Treatment Outcome
Tolerability
chemistry
Clinical diagnosis
biology.protein
Female
lipids (amino acids
peptides
and proteins)
Patient Safety
Cardiology and Cardiovascular Medicine
business
Zdroj: Atherosclerosis. 249:215-223
ISSN: 0021-9150
DOI: 10.1016/j.atherosclerosis.2016.03.017
Popis: 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).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.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.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).
Databáze: OpenAIRE
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