Efficacy and Safety of the Cholesteryl Ester Transfer Protein Inhibitor Evacetrapib in Combination With Atorvastatin in Japanese Patients With Primary Hypercholesterolemia

Abstract

the hazard ratio for total CAD increases 1.4-, 1.7-, 2.2-, and 2.8-fold when LDL-C is 2.06-2.57, 2.58-3.09, 3.10-3.61, and ≥3.62 mmol/L, respectively, compared with LDL-C <2.06 mmol/L. 5 Cholesteryl ester transfer protein (CETP) is a plasma glycoprotein secreted primarily by the liver that mediates the transfer of cholesteryl ester (CE) from high-density lipoprotein (HDL) to apolipoprotein (apo)B-rich lipoproteins (Lp; i.e., very-low-density lipoprotein [VLDL] and LDL) in exchange for their triglycerides, as well as the transfer of triglycerides/CE between apo-B-rich lipoproteins. Inhibition of CETP represents a potent mechanism for increasing HDL cholesterol (HDL-C) and lowering LDL-C. There is evidence that CETP inhibition prevents transfer of CE from HDL-C to apoB-containing lipoproteins and may increase cholesterol efflux. 6-8 The majority of animal model data indicate that CETP is proatherogenic, supporting an anti-atherogenic effect of CETP inhibitors. 8,9T he use of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors (statins) to reduce low-density lipoprotein cholesterol (LDL-C) has resulted in relative reductions in cardiovascular events of 20-30%. As a result, current guidelines for dyslipidemia management and prevention of atherosclerotic cardiovascular diseases recommend reducing LDL-C. 1-3Although LDL-C management has provided significant clinical benefits, atherosclerosis remains a major health burden in Japan, where the relative risk of coronary artery disease (CAD) has been confirmed by epidemiological studies to increase in tandem with LDL-C and total cholesterol (TC). The NIPPON DATA 80 study showed that the relative risk of death due to CAD increases 1.4-, 1.7-, 1.8-, and 3.8-fold when TC is 5.18-5.68, 5.69-6.20, 6.21-6.70, and ≥6.71 mmol/L, respectively, compared with TC 4.14-4.65 mmol/L, for men and women combined. 4 A more recent Japanese epidemiological study reported that