The class
Review reconsiders the protective reputation of HDL after the abrupt ILLUMINATE failure of torcetrapib (Biochem Pharmacol 2008)
Original title: HDL-cholesterol: is it really good? Differences between apoA-I and HDL
This review reconsiders the protective role of HDL cholesterol (HDL-C) in atherosclerosis in light of the CETP inhibitor torcetrapib, whose pivotal morbidity-and-mortality trial, ILLUMINATE, was abruptly stopped due to excess mortality in the torcetrapib arm despite raising HDL-C. While statins effectively lower LDL cholesterol and reduce cardiovascular risk, many treated patients still experience cardiovascular events, and low HDL-C remains an important independent risk factor, motivating the search for HDL-C-directed therapies to address this residual risk. The authors review HDL-C metabolic pathways and then survey emerging pharmacological approaches targeting HDL-C metabolism, aiming to put the torcetrapib disappointment in context rather than abandon the HDL-C hypothesis.
Original abstract
Since the very first report showing the regression of established atherosclerotic lesions by means of high-density lipoprotein cholesterol (HDL-C) plasma fraction, much information has been generated about the protective role of HDL-C in atherosclerosis. Nonetheless, this positive point of view about HDL has been nearly surpassed since modern informations concerning torcetrapib have appeared. Disappointment was palpable when its pivotal morbidity-and-mortality clinical trial, ILLUMINATE, was abruptly stopped due to excess mortality amongst the group randomized to receive torcetrapib. In this work we will try to put things in perspective. Lowering low-density lipoprotein cholesterol (LDL-C) levels with statins is a proven strategy for reducing the cardiovascular disease (CVD) risk. Despite the impressive benefits of statins, there remain a significant proportion of treated patients in which cardiovascular events are not prevented. Low HDL-C levels are an important independent risk factor for CVD. There is a need to develop suitable therapies to reduce this residual risk through HDL-C related mechanisms. Therefore, we will first review HDL-C pathways and we will subsequently state the new pharmacological approaches to HDL-C metabolism.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.