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Background— Although cholesteryl ester transfer protein (CETP) inhibition is regarded as a promising strategy to reduce atherosclerosis by increasing high-density lipoprotein cholesterol, the CETP inhibitor torcetrapib given in addition to atorvastatin had no effect on atherosclerosis and even increased cardiovascular death in the recent Investigation of Lipid Level Management to Understand its Impact in Atherosclerotic Events trial. Therefore, we evaluated the antiatherogenic potential and adverse effects of torcetrapib in humanized APOE*3-Leiden.CETP (E3L.CETP) mice.

Methods and Results— E3L.CETP mice were fed a cholesterol-rich diet without drugs or with torcetrapib (12 mg · kg⁻¹ · d⁻¹), atorvastatin (2.8 mg · kg⁻¹ · d⁻¹), or both for 14 weeks. Torcetrapib decreased CETP activity in both the absence and presence of atorvastatin (−74% and −73%, respectively; P<0.001). Torcetrapib decreased plasma …