Dalcetrapib
Prospective cohort data link elevated CETP concentration to higher cardiovascular risk only when triglycerides are also high (Curr Opin Lipidol 2004)
Original title: Role of CETP inhibitors in the treatment of dyslipidemia
This review summarizes human data on cholesteryl ester transfer protein (CETP) and atherosclerosis and the potential role of CETP inhibitors in treating dyslipidemia. Two small-molecule CETP inhibitors, JTT-705 and torcetrapib, had recently been shown to effectively raise HDL cholesterol without serious side effects, alone or combined with statins. Prospective data from the Epic-Norfolk study indicated that elevated CETP concentration combined with elevated triglyceride levels was associated with increased odds of cardiovascular events, and data from the Diabetes Atherosclerosis Intervention Study showed elevated CETP concentration was associated with faster progression of coronary atherosclerosis in type 2 diabetes patients using fenofibrate. The review concludes that increased CETP activity might be specifically detrimental under hypertriglyceridemic conditions, warranting further study of CETP inhibition in hypertriglyceridemic patients.
Original abstract
Purpose Of Review: This review summarizes novel human data on cholesteryl ester-transfer protein (CETP) and atherosclerosis and the possible use of CETP inhibitors in the treatment of dyslipidemia. In addition, it will underline that therapeutic targeting of the high-density lipoprotein (HDL) metabolism entails more than simply observing changes in cholesterol levels of this lipoprotein.
Recent Findings: Two pharmacological small-molecule inhibitors of CETP, JTT-705 and torcetrapib, have recently been shown to effectively raise HDL cholesterol in humans without serious side effects when either used as a monotherapy or combined with statins that lower low-density lipoprotein cholesterol. Importantly, prospective data from the Epic-Norfolk study furthermore indicate that elevated CETP concentration in conjunction with elevated triglyceride levels are associated with increased odds for cardiovascular events. Data from the Diabetic Atherosclerosis Intervention Study furthermore show that elevated CETP concentration is associated with increased progression of coronary atherosclerosis in patients with type 2 diabetes who use fenofibrate.
Summary: Long-term studies will have to show whether CETP inhibition decreases the risk of atherosclerotic disease in dyslipidemic patients. Increased CETP activity might be detrimental under hypertriglyceridemic conditions which is of importance when considering that a large proportion of patients at increased risk from coronary artery disease exhibit elevated triglyceride levels. Studies into the effects of CETP inhibition in hypertriglyceridemic patients therefore seem warranted. Awaiting the first data on the effect of CETP inhibition on surrogate endpoints for atherosclerosis, this review furthermore outlines that the complexity of HDL metabolism will necessitate a wide variety of studies on many aspects of this intriguing lipoprotein.
dalcetrapibepidemiologyHDL biologytorcetrapib
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.