Journal Article

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

Kang, Duk-Hyun, Ballantyne, Christie M., Ferreira Rossi, Paulo Roberto, Ashraf, Tanya B., Dong, Yugang, Sheu, Wayne Huey-Heng, Ye, Ping, Sapre, Aditi, Moiseeva, Yulia, Mitchel, Yale B., Tobias, Sandra C., Shah, Sukrut, Sahin, Tayfun, Briones, Ignacio Rodriguez, Johnson-Levonas, Amy O.

2017

Overview

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.

• Publisher: Elsevier Inc,Elsevier Limited
• Subject: Abnormalities / Aged / Anticholesteremic Agents - administration & dosage / Apolipoprotein B / Blood pressure / Cardiovascular / Cholesterol / Cholesterol, HDL - blood / Cholesterol, HDL - drug effects / Confidence intervals / Creatine / Creatine kinase / Density / Dose-Response Relationship, Drug / Double-Blind Method / Drug Therapy, Combination / Drug Tolerance / Enzymes / Female / Follow-Up Studies / High density lipoprotein / Humans / Hydroxymethylglutaryl-CoA Reductase Inhibitors - administration & dosage / Hypercholesterolemia / Hypercholesterolemia - blood / Hypercholesterolemia - drug therapy / Laboratories / Lipids / Liver / Low density lipoprotein / Male / Middle Aged / Oxazolidinones - administration & dosage / Patients / Randomization / Safety / Statins / Therapy / Time Factors / Treatment Outcome