Existing and emerging therapies for the treatment of familial hypercholesterolemia

Familial hypercholesterolemia (FH), an autosomal dominant disorder of LDL metabolism that is characterized by elevated LDL-cholesterol, is commonly encountered in patients with atherosclerotic coronary heart disease. Combinations of cholesterol-lowering therapies are often used to lower LDL-cholesterol in patients with FH; however, current treatment goals for LDL-cholesterol are rarely achieved in patients with homozygous FH (HoFH) and are difficult to achieve in patients with heterozygous FH (HeFH). Therapies that lower LDL-cholesterol through LDL receptor-mediated mechanisms have thus far been largely ineffective in patients with HoFH, particularly in those with negligible (<2%) LDL receptor activity. Among patients with HeFH who were at very high risk for atherosclerotic cardiovascular disease events, combined therapy consisting of a high dose of high-intensity statin, ezetimibe, and proprotein convertase subtilisin Kexin type 9 inhibitor failed to lower LDL-cholesterol to minimal acceptable goals in more than 50%. This article provides a framework for the use of available and emerging treatments that lower LDL-cholesterol in adult patients with HoFH and HeFH. A framework is provided for the use of angiopoietin-like protein 3 inhibitors in the treatment of HoFH and HeFH.