Efficacy and safety of the cholesteryl ester transfer protein inhibitor anacetrapib as monotherapy and coadministered with atorvastatin in dyslipidemic patients.

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 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 ∼70% lowering of LDL-C and more than doubling of HDL-C. Anacetrapib was generally well tolerated with no discernable effect on blood pressure.