A review argues the off-target effects of torcetrapib, not the CETP-inhibition mechanism itself, likely overrode any cardiovascular benefit (Cardiol Clin 2008)

Despite major progress in managing coronary heart disease (CHD), a significant number of fatal and nonfatal CHD events persist, motivating continued interest in low HDL cholesterol as a modifiable risk factor. This review argues that although the torcetrapib experience was a major setback for CETP inhibition and HDL-targeted therapeutics broadly, it was not necessarily fatal to the field, since the off-target effects of torcetrapib appear substantial enough to have overridden any potential cardiovascular benefit of CETP inhibition itself. Despite continued uncertainty about the cardiovascular implications of both genetic CETP deficiency and pharmacologic CETP inhibition, the authors argue there remain reasons to believe that CETP inhibitors free of off-target toxicity could still improve plasma lipids and reduce cardiovascular risk.