Lipoprotein apheresis in the management of familial hypercholesterolaemia: historical perspective and recent advances.

At present, lipoprotein apheresis, combined with high-dose statin and ezetimibe therapy, is the best available means of treating patients with homozygous and statin-refractory heterozygous familial hypercholesterolaemia (FH). However, the extent of cholesterol-lowering achieved is often insufficient to meet the targets set by current guidelines. The recent advent of three new classes of lipid-lowering agents provides new hope that the latter objective may now be achievable. These compounds act either by reducing low-density lipoprotein (LDL) production by inhibiting apolipoprotein B synthesis with an antisense oligonucleotide (mipomersen) or by inhibiting microsomal triglyceride transfer protein (lomitapide), or by enhancing LDL catabolism via monoclonal antibody-mediated inhibition of the activity of proprotein convertase subtilisin/kexin 9 (PCSK9) (evolocumab). Depending on the outcome of current trials, it seems likely that these compounds, used alone or combined with lipoprotein apheresis, will markedly improve the management of refractory FH.