title: Lipid-Modifying Efficacy and Tolerability of Anacetrapib Added to Ongoing Statin Therapy in Patients with Hypercholesterolemia or Low High-Density Lipoprotein Cholesterol.
abstract: 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.
authors.affiliation: Section of Cardiovascular Research, Department of Medicine, Baylor College of Medicine, Houston, Texas. Electronic address: cmb@bcm.edu.
authors.forename: Christie M
authors.initials: CM
authors.lastname: Ballantyne
authors.affiliation: Merck Research Laboratories, Global Clinical Development, Cardiovascular Disease, Kenilworth, New Jersey.
authors.forename: Sukrut
authors.initials: S
authors.lastname: Shah
authors.affiliation: Merck Research Laboratories, Global Clinical Development, Cardiovascular Disease, Kenilworth, New Jersey.
authors.forename: Uma
authors.initials: U
authors.lastname: Kher
authors.affiliation: Merck Research Laboratories, Global Clinical Development, Cardiovascular Disease, Kenilworth, New Jersey.
authors.forename: John A
authors.initials: JA
authors.lastname: Hunter
authors.affiliation: Merck Research Laboratories, Global Clinical Development, Cardiovascular Disease, Kenilworth, New Jersey.
authors.forename: Geraldine G
authors.initials: GG
authors.lastname: Gill
authors.affiliation: Merck Research Laboratories, Global Clinical Development, Cardiovascular Disease, Kenilworth, New Jersey.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Cressman
authors.affiliation: Merck Research Laboratories, Global Clinical Development, Cardiovascular Disease, Kenilworth, New Jersey.
authors.forename: Tanya B
authors.initials: TB
authors.lastname: Ashraf
authors.affiliation: Merck Research Laboratories, Global Clinical Development, Cardiovascular Disease, Kenilworth, New Jersey.
authors.forename: Amy O
authors.initials: AO
authors.lastname: Johnson-Levonas
authors.affiliation: Merck Research Laboratories, Global Clinical Development, Cardiovascular Disease, Kenilworth, New Jersey.
authors.forename: Yale B
authors.initials: YB
authors.lastname: Mitchel
mesh_terms: D000368:Aged; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D053480:Cholesterol Ester Transfer Proteins / Q000037:antagonists & inhibitors; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D050171:Dyslipidemias / Q000097:blood / Q000188:drug therapy; D000069438:Ezetimibe / Q000627:therapeutic use; D005260:Female; D058607:Fibric Acids / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009525:Niacin / Q000627:therapeutic use; D023303:Oxazolidinones / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000924:Anticholesteremic Agents; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D058607:Fibric Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D023303:Oxazolidinones; D009525:Niacin; D000069438:Ezetimibe; C530884:anacetrapib