Ezetimibe and bile acid sequestrants: impact on lipoprotein metabolism and beyond

Purpose of review Several lines of evidence indicate that the enterocyte plays a pivotal role in cholesterol homeostasis. The development of the selective inhibitor of cholesterol absorption ezetimibe and bile acid sequestrants (BAS) interrupting the enterohepatic circulation of bile salts has expanded the options for preventing and treating cardiovascular disease. We discuss here a selection of recently published studies that evaluated the effects of ezetimibe and BAS on lipoprotein metabolism. Recent findings Although significant progress has been made in recent years in elucidating the impacts of ezetimibe and BAS on lipoprotein metabolism, underlying mechanisms are not completely understood. Important new insights have been provided by using in-vivo kinetic studies of apolipoproteins labelled with a stable isotope. Other reports indicated that ezetimibe and BAS modulate the expression of several key genes involved in intestinal lipoprotein metabolism. Many of these effects have been related to the local effects of ezetimibe and BAS on intestinal cholesterol homeostasis. Summary A substantial effort is being made by researchers to fully understand the mechanisms by which ezetimibe and BAS improve lipid profile. The efficacy of combination therapy of statins with ezetimibe or BAS for the prevention of cardiovascular disease remains to be confirmed in clinical endpoint studies.