Familial hypercholesterolemia (FH) is a common genetic disorder that can manifest clinically as both the severe homozygous (HoFH) form that often presents in childhood and the commoner heterozygous (HeFH) form that is typically identified in adults. The majority of genetic causes are due to defects in low-density lipoprotein (LDL) receptor synthesis and action. Until recently, it was exceedingly difficult to achieve the goal of a 50% reduction in LDL-cholesterol or LDL-C < 70-100 in these patients. Established therapies include statins, niacin, bile-acid sequestrants, and ezetimibe in various combinations. The recent advent of monoclonal antibodies to PCSK9 (evolocumab and alirocumab) has revolutionized the management of FH and results in a substantial reduction in LDL-C and also reductions in Lp(a). In addition, the previous ushering in of antisense therapy against apoB (mipomersen) and inhibition of microsomal transfer protein (lomitapide) for use in HoFH greatly enhanced our ability to manage refractory hypercholesterolemia in these patients. Hence, the therapeutic landscape for this common disorder has changed dramatically for these patients, with a strong promise for a reduction in cardiovascular events.
Keywords: FH; LDL cholesterol/LDL; PCSK9; atherosclerosis; familial hypercholesterolemia; prevention.