Lipid-Modifying Efficacy and Tolerability of Anacetrapib Added to Ongoing Statin Therapy in Patients with Hypercholesterolemia or Low High-Density Lipoprotein Cholesterol

Am J Cardiol. 2017 Feb 1;119(3):388-396. doi: 10.1016/j.amjcard.2016.10.032. Epub 2016 Nov 1.


To assess the effects of anacetrapib added to statin ± other lipid-modifying therapies in patients with hypercholesterolemia and not at their low-density lipoprotein cholesterol (LDL-C) goal (as per National Cholesterol Education Program Adult Treatment Panel III [NCEP ATP III] guidelines) and in those with low high-density lipoprotein cholesterol (HDL-C). Patients on a stable dose of moderate/high-intensity statin ± other lipid-modifying therapies with LDL-C ≥70, ≥100, ≥130, or ≥160 mg/dl for very high, high, moderate, and low coronary heart disease risk, respectively, or at LDL-C goal with HDL-C ≤40 mg/dl, were randomized 1:1:1, stratified by background therapy use, to anacetrapib 100 mg (n = 153), anacetrapib 25 mg (n = 152), or placebo (n = 154) for 24 weeks, followed by a 12-week off-drug reversal phase. The primary end points were percent change from baseline in LDL-C (beta-quantification method) and HDL-C, as well as the safety profile of anacetrapib. Both doses of anacetrapib reduced LDL-C, non-HDL-C, apolipoprotein (Apo) B, and lipoprotein a and increased HDL-C and Apo AI versus placebo (p <0.001 for all). There were no meaningful differences between the anacetrapib 25 mg, 100 mg, and placebo groups in the proportions of discontinuations due to drug-related adverse events (0.7%, 1.3% vs 1.3%) or in abnormalities in liver enzymes (0%, 0% vs 0.7%), creatine kinase elevations overall (0%, 0.7% vs 0%) or with muscle symptoms (none seen), blood pressure, electrolytes, or adjudicated cardiovascular events (0.7%, 0.7% vs 1.3%). In conclusion, treatment with anacetrapib resulted in substantial reductions in LDL-C and increases in HDL-C and was generally well tolerated.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Anticholesteremic Agents / therapeutic use*
  • Cholesterol Ester Transfer Proteins / antagonists & inhibitors
  • Cholesterol, HDL / blood
  • Cholesterol, LDL / blood
  • Double-Blind Method
  • Drug Therapy, Combination
  • Dyslipidemias / blood
  • Dyslipidemias / drug therapy
  • Ezetimibe / therapeutic use
  • Female
  • Fibric Acids / therapeutic use
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Hypercholesterolemia / blood
  • Hypercholesterolemia / drug therapy*
  • Male
  • Middle Aged
  • Niacin / therapeutic use
  • Oxazolidinones / therapeutic use*
  • Treatment Outcome


  • Anticholesteremic Agents
  • Cholesterol Ester Transfer Proteins
  • Cholesterol, HDL
  • Cholesterol, LDL
  • Fibric Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Oxazolidinones
  • Niacin
  • Ezetimibe
  • anacetrapib