Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

Abstract

Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .).

Evaluating the relationship between circulating lipoprotein lipids and apolipoproteins with risk of coronary heart disease: A multivariable Mendelian randomisation analysis

“…Based on these and recent data [15,26], the primary focus of lipid-modifying therapies ought to be the reduction in number of atherogenic lipoproteins (as measured by apolipoprotein B) rather than the reduction in cholesterol or triglycerides. This is especially the case when drugs have discrepant effects across these lipid traits [10,15,66]. Thus, in predicting the cardiovascular efficacy of a lipid-modifying therapeutic, apolipoprotein B can, all things being equal, be used as a reliable surrogate marker for the expected relative risk reduction in CHD-assuming, of course, that the drug under investigation does not display adverse events that arise either from target-mediated mechanisms or from off-target effects (notably, both can be investigated in human genetics studies [67]).…”

Unexplained reciprocal regulation of diabetes and lipoproteins

“…On the contrary, two different inhibitors of CETP, as well as genetic CETP deficiency, are associated with improved glycemia [35]. Moreover, recent data from the REVEAL trial – which had 4.1 years of follow-up – showed that Anacetrapib raised HDL-cholesterol and lowered LDL-cholesterol while reducing new-onset diabetes and HbA1c [36▪▪]. These findings suggest the possibility that CETP inhibition, or raising HDL-cholesterol more generally, has a beneficial effect on glycemia that is independent of, or counteracts against, the effects of LDL-cholesterol-lowering.…”

Interaction of lecithin-cholesterol acyltransferase with lipid surfaces and apolipoprotein A-I derived peptides: implications for the cofactor mechanism of apolipoprotein A-I

“…This process is termed as reverse cholesterol transport (RCT) (Lewis and Rader, 2005;Tall, 1998). However, there is a growing body of literature showing that the elevation of the HDL-C by niacins or cholesterol ester transfer protein inhibitors does not or only moderately improve cardiovascular events (Group, 2017;Rader and Hovingh, 2014;Tall and Rader, 2017). In addition, recent genetic association studies have raised doubts towards the HDL-C hypothesis and causality of HDL-C in the development of CHD (Haase et al, 2012;Peloso et al, 2014;Rader and Hovingh, 2014).…”