Torcetrapib
A review previews a large-scale CETP-inhibitor imaging and outcomes program as the next frontier after statin-driven atherosclerosis regression (Can J Cardiol 2006)
Original title: Prevention challenges: the era of atherosclerosis regression
This review discusses the era of atherosclerosis regression enabled by statins, which slow progression and reduce cardiovascular events by roughly one-third, while noting that an aging population and rising rates of metabolic syndrome and diabetes are increasing the atherosclerosis burden and driving the need for complementary therapies. While some targets, such as acyl-coenzyme A:cholesterol acyltransferase inhibition, have disappointed clinically, strong evidence linking low HDL cholesterol to cardiovascular risk supports HDL-targeted approaches including direct HDL infusions, HDL mimetics, and CETP inhibition, which the author calls particularly promising. The CETP inhibitor torcetrapib raises HDL cholesterol by 40% to 60% while modestly lowering LDL cholesterol, and the review previews that combining the HDL-raising effect of CETP inhibition with the LDL-lowering effect of a statin was then being extensively evaluated through several imaging studies and a large-scale clinical endpoint trial.
Original abstract
Statins slow atherosclerosis progression and can even induce atherosclerosis regression. The reduction of cardiovascular events with statins by approximately one-third demonstrates not only their clinical efficacy but also the unmet clinical need. The aging of the population and the epidemics of the metabolic syndrome and diabetes contribute to the increasing burden of atherosclerosis in society, and fuel the need for novel complementary therapies to further improve clinical outcomes. Some targets, such as acyl-coenzyme A:cholesterol acyltransferase inhibition, have yielded disappointing clinical results. In contrast, there is strong evidence linking lower high density lipoprotein (HDL) cholesterol levels and greater cardiovascular risk, thus providing the rationale for targeting HDL in the prevention and treatment of cardiovascular diseases. Therapeutic approaches include direct infusions of HDL cholesterol or HDL-mimetic agents, as well as the inhibition of cholesteryl ester transfer protein (CETP). CETP inhibition appears to be one particularly promising strategy. The CETP inhibitor torcetrapib increases plasma HDL cholesterol levels by 40% to 60%, while modestly decreasing low density lipoprotein (LDL) cholesterol. Combining the HDL cholesterol-elevating properties of a CETP inhibitor with the LDL cholesterol-lowering properties of a statin may offer improved outcomes over targeting LDL cholesterol alone. This hypothesis is being extensively evaluated in a comprehensive program that involves several imaging studies and a large-scale clinical end point trial. The additional cardiovascular protection required for patients with atherosclerosis or risk equivalents will likely be provided by therapies that go beyond LDL reduction.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.