Anacetrapib
Phase 2 dose-ranging trial finds anacetrapib plus atorvastatin cuts LDL-C by 70% and more than doubles HDL-C (Am Heart J 2009)
Original title: Efficacy and safety of the cholesteryl ester transfer protein inhibitor anacetrapib as monotherapy and coadministered with atorvastatin in dyslipidemic patients
A total of 589 patients with primary hypercholesterolemia or mixed hyperlipidemia (53.8% with low HDL-C) were randomized equally to ten groups: five received background atorvastatin 20 mg and five did not, each further randomized to placebo or anacetrapib 10, 40, 150, or 300 mg once daily for 8 weeks. For placebo and increasing anacetrapib monotherapy doses, least squares mean percent changes from baseline to week 8 in LDL-C were 2%, -16%, -27%, -40%, and -39%, and in HDL-C were 4%, 44%, 86%, 139%, and 133% (P less than .001 vs placebo for all doses). Co-administration with atorvastatin produced significant incremental LDL-C reductions and similar HDL-C increases versus atorvastatin alone, consistent across baseline triglyceride strata, with the combination achieving roughly 70% LDL-C lowering and more than doubled HDL-C overall. Anacetrapib was well tolerated with adverse event rates similar to placebo and no increase in systolic or diastolic blood pressure in any arm.
Original abstract
Background: High-density lipoprotein cholesterol (HDL-C) levels are inversely associated with cardiovascular risk. Cholesteryl ester transfer protein inhibition is one strategy for increasing HDL-C. This study evaluated the lipid-altering efficacy and safety of the cholesteryl ester transfer protein inhibitor anacetrapib as monotherapy or coadministered with atorvastatin in patients with dyslipidemia.
Methods: A total of 589 patients with primary hypercholesterolemia or mixed hyperlipidemia (53.8% of the study population had low HDL-C) were randomized equally to one of 10 groups: 5 groups received background statin therapy of atorvastatin 20 mg and 5 did not, and each of these was randomized to placebo, anacetrapib 10, 40, 150, and 300 mg once daily for 8 weeks. An equal proportion of patients had triglycerides >150 mg/dL in each group.
Results: For placebo and anacetrapib monotherapy (10, 40, 150, and 300 mg), least squares mean percent changes from baseline to week 8 for low-density lipoprotein cholesterol (LDL-C) were 2%, -16%, -27%, -40%, and -39%, respectively, and for HDL-C were 4%, 44%, 86%, 139%, and 133%, respectively (P < .001 vs placebo for all doses). Coadministration of anacetrapib with atorvastatin produced significant incremental LDL-C reductions and similar HDL-C increases versus atorvastatin monotherapy. For both anacetrapib monotherapy and coadministration with atorvastatin, the LDL-C reductions were similar in patients with baseline triglyceride levels greater than and less than or equal to the median. Anacetrapib was well tolerated, and the incidence of adverse events was similar for placebo and all active treatment groups. There were no increases in systolic or diastolic blood pressure in any treatment arm.
Conclusions: Anacetrapib, as monotherapy or coadministered with atorvastatin, produced significant reductions in LDL-C and increases in HDL-C; the net result of treatment with anacetrapib + atorvastatin was approximately 70% lowering of LDL-C and more than doubling of HDL-C. Anacetrapib was generally well tolerated with no discernable effect on blood pressure.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.