The class
Review ranks CETP and ANGPTL3 inhibition among the most promising novel LDL-lowering strategies (Curr Opin Lipidol 2018)
Original title: Genetics of familial hypercholesterolemia: a tool for development of novel lipid lowering pharmaceuticals?
This review surveys pharmaceuticals targeting the roughly 80 genes associated with hypercholesterolaemia beyond the LDL receptor mutations that cause familial hypercholesterolaemia. Of these many potential targets, only inhibitors of cholesteryl ester transfer protein (CETP), angiopoietin-related protein 3 (ANGPTL3), and apolipoprotein C-III have reached clinical trials. Both CETP and ANGPTL3 inhibition lowered LDL cholesterol, with ANGPTL3 inhibition showing the largest effect and remaining effective even in familial hypercholesterolaemia patients, while the effect of apoC-III inhibition on LDL cholesterol was inconclusive. The authors conclude CETP and ANGPTL3 inhibitors are promising novel LDL-lowering treatment options, while apoC-III inhibition needs further research.
Original abstract
Purpose Of Review: Familial hypercholesterolemia is characterized by high LDL cholesterol and an elevated risk to develop coronary heart disease. Mutations in LDL receptor-mediated cholesterol uptake are the main cause of familial hypercholesterolemia. However, multiple mutations in various other genes are also associated with high LDL cholesterol and even familial hypercholesterolemia. Thus, pharmaceuticals that target these genes and proteins might be attractive treatment options to reduce LDL cholesterol. This review provides an overview of the recent developments and clinical testing of such pharmaceuticals.
Recent Findings: About 80 genes are associated with hypercholesterolemia but only pharmaceuticals that inhibit cholesteryl ester transfer protein (CETP), angiopoietin-related protein 3 (ANGPTL3), and apolipoprotein C-III (apoC-III) have recently been tested in clinical trials. Inhibition of CETP and ANGPTL3 lowered LDL cholesterol. ANGPTL3 inhibition had the largest effect and was even effective in familial hypercholesterolemia patients. The effect of apoC-III inhibition on LDL cholesterol is not conclusive.
Summary: Of the many potential pharmaceutical targets involved in LDL cholesterol, only a few have been studied so far. Of these, pharmaceuticals that inhibit CETP or ANGPTL3 are promising novel treatment options to reduce LDL cholesterol but the effect of apoC-III inhibition requires more research.
the classfamilial hypercholesterolaemia
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.