Dalcetrapib: turning the tide for CETP inhibition?

摘要

In the search for additional cardiovascular-risk lowering strategies on top of statins, raising high-density lipoprotein cholesterol (HDL-C) is an attractive target. HDL-C inversely correlates with cardiovascular risk, and novel mechanisms by which HDL-C might protect against atherosclerotic cardiovascular disease are reported regularly.1 The quest for selective HDL-C raising compounds has, however, been hindered by the complexity of HDL-C metabolism. Despite controversial data on the role of cholesteryl ester transfer protein (CETP) in atherosclerosis, the impressive increase in concentrations of HDL-C after CETP inhibition has raised expectations for drugs of the CETP inhibitor class. But the ILLUMINATE2 study was prematurely terminated in 2006 because of an increased cardiovascular event rate in patients receiving the CETP inhibitortorcetrapib, which led to a fall in the popularity of CETP inhibition as a therapeutic target, while also casting a broader shadow on the attractiveness of raising HDL-C concentrations.