A Multiregional, Randomized Evaluation of the Lipid-Modifying Efficacy and Tolerability of Anacetrapib Added to Ongoing Statin Therapy in Patients With Hypercholesterolemia or Low High-Density Lipoprotein Cholesterol


Ballantyne C. M. , Shah S., Sapre A., Ashraf T. B. , Tobias S. C. , ŞAHİN T. , et al.

AMERICAN JOURNAL OF CARDIOLOGY, cilt.120, ss.569-576, 2017 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Cilt numarası: 120 Konu: 4
  • Basım Tarihi: 2017
  • Doi Numarası: 10.1016/j.amjcard.2017.03.255
  • Dergi Adı: AMERICAN JOURNAL OF CARDIOLOGY
  • Sayfa Sayısı: ss.569-576

Özet

This phase 3, multiregional, randomized, double-blind, placebo-controlled study assessed the efficacy/safety profile of anacetrapib added to ongoing therapy with statin +/- other lipid-modifying therapies in patients with hypercholesterolemia who were not at their low-density lipoprotein (LDL-C) goal (as per the National Cholesterol Education Program Adult Treatment Panel III guidelines) and in those with low high-density lipoprotein cholesterol (HDL-C). Patients on a stable dose of statin +/- other lipid-modifying therapies and with LDL-C >= 70 to <115, >= 100 to <145, >= 130, or >= 160 mg/dl for very high, high, moderate, or low CHD risk or at LDL-C goal (per CHD risk category) with HDL-C <= 40 mg/dl were randomized in a ratio of 1:1 to anacetrapib 100 mg (n = 290) or placebo (n = 293) for 24 weeks, followed by a 12-week off-drug phase. The co-primary end points were % change from baseline in LDL-C and HDL-C and the safety profile of anacetrapib. Treatment with anacetrapib reduced LDL-C (BQ) by 37% (95% confidence interval -42.5, -31.0) and increased HDL-C by 118% (95% confidence interval 110.6, 125.7) relative to placebo (p <0.001 for both). Anacetrapib also reduced non-HDL-C, apolipoprotein B, and lipoprotein a and increased apolipoprotein AI versus placebo (p <0.001 for all). There were no clinically meaningful differences between the anacetrapib and placebo groups in the % patients who discontinued drug due to an adverse event or in abnormalities in liver enzymes, creatine kinase, blood pressure, electrolytes, or adjudicated cardiovascular events. Treatment with anacetrapib substantially reduced LDL-C and also increased HDL-C and was well tolerated over 24 weeks in statin-treated patients with hypercholesterolemia or low HDL-C. (C) 2017 Merck Sharp & Dohme Corp. and the Authors. Published by Elsevier Inc.