Avasimibe, an ACAT inhibitor, enhances the lipid lowering effect of atorvastatin in subjects with homozygous familial hypercholesterolemia

This study assessed the efficacy and safety of avasimibe (CI-1011), an inhibitor of acyl coenzyme A-cholesterol acyltransferase (ACAT) in subjects with homozygous familial hypercholesterolemia (HoFH). Twenty seven subjects were enrolled in a double-blind, randomized, 3-sequence crossover trial of atorvastatin 80 mg QD, avasimibe 750 mg QD, and the combined treatment of atorvastatin 80 mg QD and avasimibe 750 mg QD after a washout period of 4 weeks. Each treatment period was administered over 6 weeks for a total of 18 weeks. There were no significant lipid changes resulting from the administration of avasimibe monotherapy. Avasimibe in combination with atorvastatin resulted in a significantly better reduction of total cholesterol (TC) as compared to atorvastatin alone (−22% versus −18%) (<F>P<0.05</F>). All other lipid changes were not statistically significant for combination therapy compared to atorvastatin monotherapy, however there were greater reductions in triglycerides (TG) (−24% versus −13%), low-density lipoprotein cholesterol (LDL-C) (−23% versus −19%), very low-density lipoprotein cholesterol (VLDL-C) (−24% versus −13%) and high-density lipoprotein cholesterol (HDL-C) (−11% versus −6%). Avasimibe may modestly enhance the lipid-reducing effect of atorvastatin by further inhibiting the production of intracellular cholesterol through mechanisms that appear to be compatible in this population. [Copyright &y& Elsevier]