Why Have CETP Inhibitors Failed in Clinical Trials?

The degree of LDL-cholesterol lowering may not matter as much as how it is lowered, specifically the corresponding absolute reduction in apolipoprotein B.

Cholesteryl ester transfer protein (CETP) inhibitors significantly raise HDL cholesterol (HDL-C) and lower LDL cholesterol (LDL-C) but do not reduce risk for cardiovascular events. To explore why, researchers evaluated the cardiovascular risk associated with different HDL-C, LDL-C, and apolipoprotein (apoB) levels conferred by variants in the CETP gene and the 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) gene.

Using genetic data from 102,837 participants in 14 North American and U.K. studies (1948–2012), they conducted Mendelian randomization analyses of CETP and HMGCR scores (calculated by weighting the effect of HDL alleles on HDL-C), other lipid and lipoprotein changes, and cardiovascular events. The associations were externally valid…

Reviewing Author

Karol E. Watson, MD, PhD, FACC

Disclosures

Consultant/Advisory BoardBoehringer Ingelheim; Amgen; Novartis; Lilly; Amarin

Speaker’s BureauBoehringer Ingelheim

Grant/Research SupportNIH

Editorial BoardsCirculation (Associate Editor)