The class
Review notes CETP inhibitors raise HDL-C by 31-138 percent, but whether this lowers coronary risk remains unresolved (Circ J 2013)
Original title: Therapeutic approaches to the regulation of metabolism of high-density lipoprotein. Novel HDL-directed pharmacological intervention and exercise
This review surveys therapeutic approaches to raising HDL cholesterol as a complement to statin-driven LDL-C lowering, given that patients on high-dose statins, especially in secondary prevention, remain at high cardiovascular risk regardless of their achieved LDL-C level. It notes that cholesteryl ester transfer protein (CETP) inhibitors substantially raise HDL-C, by 31 to 138 percent depending on the agent, but that it remains unclear whether CETP inhibitors reduce the cardiovascular risk associated with low HDL-C, in contrast to reconstituted HDL or apolipoprotein A-I mimetic peptides, which are described as improving HDL functionality directly. The review concludes lifestyle changes, including exercise, which raises HDL2-C through multiple mechanisms, should remain the first option for correcting HDL-related metabolic disorders.
Original abstract
High-density lipoprotein (HDL) and low-density lipoprotein (LDL) particles transport cholesterol in plasma and play an important role in cellular cholesterol homeostasis, which influences cell function. The risk of coronary artery disease (CAD) associated with high levels of LDL-cholesterol (LDL-C) can be reduced by treatment with statins, which reduce LDL-C levels by inhibiting cellular cholesterol synthesis. However, patients who are treated with high doses of statins, especially secondary CAD prevention, regardless of their resulting LDL-C levels, are still at high risk of CAD. Therefore, there has been growing interest in HDL-directed therapies. Inhibitors of cholesteryl ester transfer protein (CETP) substantially increase HDL-C levels (by 31-138%). However, it is still unclear whether or not CETP inhibitors can reduce the risk of CAD associated with low HDL-C levels, while reconstituted HDL or apolipoprotein A-I mimetic peptides increase the functionality of HDL. Low levels of HDL-C are often complicated with metabolic disorders, including hypertriglyceridemia, metabolic syndrome, and type 2 diabetes mellitus, and lifestyle changes are effective for correcting these conditions. Physical activity and exercise training increase HDL-C levels, especially HDL2-C levels, by multiple mechanisms. Therefore, although using HDL-directed therapies that increase HDL-C levels and/or improve the function of HDL is a reasonable approach for reducing the residual risk of CAD as a complement to LDL-C-lowering therapy, lifestyle modifications including exercise to improve metabolic disorders should be considered as the first option.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.