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

• Published in: The American journal of cardiology Vol. 120; no. 4; pp. 569 - 576
• Main Authors: Ballantyne, Christie M., Shah, Sukrut, Sapre, Aditi, Ashraf, Tanya B., Tobias, Sandra C., Sahin, Tayfun, Ye, Ping, Dong, Yugang, Sheu, Wayne Huey-Heng, Kang, Duk-Hyun, Ferreira Rossi, Paulo Roberto, Moiseeva, Yulia, Briones, Ignacio Rodriguez, Johnson-Levonas, Amy O., Mitchel, Yale B.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.08.2017; Elsevier Limited
• Subjects: Abnormalities; Aged; Anticholesteremic Agents - administration & dosage; Apolipoprotein B; Blood pressure; 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; Brazil; Mexico; Turkey; China; Taiwan; Russia
• ISSN: 0002-9149; 1879-1913
• DOI: 10.1016/j.amjcard.2017.03.255

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.