Anacetrapib: potential for the prevention and treatment of coronary heart disease

Dylan L Steen,1 Amit V Khera,2 Christopher P Cannon1 1TIMI Study Group, Cardiovascular Division, 2Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USA Abstract: Despite major advances in cardiovascular care in recent decades, atherosclerotic cardiovascular disease remains the leading cause of morbidity and mortality worldwide. Statins have been shown to reduce cardiovascular events by 25%–40% in a dose-dependent fashion; yet additional therapies are needed to reduce vascular disease progression and acute thrombotic events. In addition to low-density lipoprotein cholesterol (LDL-C) reduction, other lipid risk factors, such as low high-density lipoprotein cholesterol (HDL-C), have created interest as therapeutic targets to lower cardiovascular risk. However, the absence of compelling data for incremental benefit of non-LDL-centric therapies in the statin era has limited their clinical use. A novel class of compounds, cholesteryl ester transfer protein (CETP) inhibitors, has demonstrated many potentially beneficial lipid-modifying effects. While in vitro and animal data for CETP inhibition have been encouraging, the initial enthusiasm for the class has been tempered by the failure of two CETP inhibitors (torcetrapib and dalcetrapib) in Phase III trials to reduce cardiovascular outcomes. Anacetrapib, a compound that causes near-complete CETP inhibition, has among its effects, robust reductions in LDL-C and lipoprotein(a) as well as dramatic increases in HDL-C. The ability of anacetrapib to reduce coronary disease events is being tested in the Randomized EValuation of the Effects of Anacetrapib Through Lipid-modification (REVEAL) trial (NCT01252953). Keywords: anacetrapib, cholesteryl ester transfer protein, cholesteryl ester transfer protein inhibitor, atherosclerosis