title: Efficacy and safety of the cholesteryl ester transfer protein inhibitor anacetrapib in Japanese patients with heterozygous familial hypercholesterolemia.
abstract: 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).
authors.affiliation: National Center Geriatrics and Gerontology, 7-430 Morioka-cho, Obu-city, Aichi, Japan. Electronic address: harai@ncgg.go.jp.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Arai
authors.affiliation: Teikyo Academic Research Center, Teikyo University, 2-11-1, Kaga, Itabashi-ku, Tokyo, Japan. Electronic address: ttera@med.teikyo-u.ac.jp.
authors.forename: Tamio
authors.initials: T
authors.lastname: Teramoto
authors.affiliation: Department of Cardiovascular Medicine, School of Medicine, Juntendo University, 2-1-1, Hongo, Bunkyo-ku, Tokyo, Japan. Electronic address: daida@juntendo.ac.jp.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Daida
authors.affiliation: Division of Anti-aging and Vascular Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa-city, Saitama, Japan. Electronic address: kikewaki@hotmail.com.
authors.forename: Katsunori
authors.initials: K
authors.lastname: Ikewaki
authors.affiliation: MSD K.K., Kitanomaru Square, 1-13-12 Kudan-kita, Chiyoda-ku, Tokyo, Japan. Electronic address: yuko.maeda@merck.com.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Maeda
authors.affiliation: MSD K.K., Kitanomaru Square, 1-13-12 Kudan-kita, Chiyoda-ku, Tokyo, Japan. Electronic address: mariko.nakagomi@merck.com.
authors.forename: Mariko
authors.initials: M
authors.lastname: Nakagomi
authors.affiliation: MSD K.K., Kitanomaru Square, 1-13-12 Kudan-kita, Chiyoda-ku, Tokyo, Japan.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Shirakawa
authors.affiliation: MSD K.K., Kitanomaru Square, 1-13-12 Kudan-kita, Chiyoda-ku, Tokyo, Japan. Electronic address: taro.kakikawa@merck.com.
authors.forename: Taro
authors.initials: T
authors.lastname: Kakikawa
authors.affiliation: MSD K.K., Kitanomaru Square, 1-13-12 Kudan-kita, Chiyoda-ku, Tokyo, Japan; Nippon Boehringer Ingelheim Co. Ltd, 2-1-1 Osaki, Shinagawa-ku, Tokyo 141-6017, Japan. Electronic address: hiro.numaguchi@gmail.com.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Numaguchi
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ, USA. Electronic address: amy_levonas@merck.com.
authors.forename: Amy O
authors.initials: AO
authors.lastname: Johnson-Levonas
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ, USA. Electronic address: sanskruti_vaidya@merck.com.
authors.forename: Sanskruti
authors.initials: S
authors.lastname: Vaidya
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ, USA. Electronic address: robert_blaustein@merck.com.
authors.forename: Robert O
authors.initials: RO
authors.lastname: Blaustein
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D053480:Cholesterol Ester Transfer Proteins / Q000037:antagonists & inhibitors*; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D006720:Homozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000188:drug therapy*; D007564:Japan; D008297:Male; D008875:Middle Aged; D023303:Oxazolidinones / Q000627:therapeutic use*; D061214:Patient Safety; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D023303:Oxazolidinones; C530884:anacetrapib
keywords: Anacetrapib; Cholesteryl ester protein inhibitor; Heterozygous familial hypercholesterolemia; High-density lipoprotein cholesterol; Low-density lipoprotein cholesterol