Heart disease remains the principal cause of death in the world and the incidence has increased in each of the last 60 years. Despite the widespread utilization of statins, and the overall reduction in serum cholesterol, one in four people will die of ischemic heart disease or stroke globally.
Cholesterol Ester Transfer Protein (CETP) inhibitors have been developed following the recognition of an association of CETP polymorphisms and changes in HDL-c in Japan.
Dalcetrapib (originally developed by Japan Tobacco, Roche) is one of four CETP inhibitors to have reached full-scale development. Others are torcetrapib (Pfizer), anacetrapib (Merck) and evacetrapib (Eli Lilly). Over 17,000 patients have participated in dalcetrapib clinical trials with more than 10,000 having received dalcetrapib. A large, double blind cardiovascular (CV) study, dal-Outcomes, randomized over 15,000 patients already taking statins for cholesterol control. However, the study results were equivocal—while the drug was well tolerated, there was no significant reduction in CV events in the dalcetrapib group, and the dalcetrapib development program was terminated.