Lipoprotein apheresis in the era of new lipid-lowering therapies

During the 1960s, in a pioneering way, plasmapheresis was used to treat children with homozygous familial hypercholesterolaemia (HoFH). Over the years, apheresis has evolved to increasingly selective methods, which have been used in paediatric HoFH since the 1990s. Today, lipoprotein apheresis (LA) is able to selectively remove atherogenic apoB100-containing lipoproteins from the blood: the main component of LDL-cholesterol, VLDL-cholesterol, and lipoprotein(a). Lipoprotein apheresis has demonstrated protective effects in the endothelium and microcirculation, prevention of the development of new aortic and coronary lesions in HoFH, reducing the incidence of major cardiovascular events, and proving helpful in subjects who fail to reach the LDL-cholesterol target or who have elevated lipoprotein(a) levels in secondary prevention. Although advances in pharmacological therapies (proprotein convertase subtilisin/kexin Type 9 inhibitors, antisense oligonucleotides, and siRNA-based treatments) have expanded the options for lipid management, LA remains a safe therapeutic approach for patients with severe lipid disorders, including HoFH, to reduce their cardiovascular risks. Currently, to put LA into perspective, some obstacles need to be overcome, including (i) the underdiagnosis of HoFH and high lipoprotein(a) level; (ii) therapeutic inertia resulting from the use of new lipid-lowering drugs with partial achievement of lipid targets; and (iii) availability of qualified LA centres and practitioners. Further prospective studies may prove useful to identify other therapeutic scenarios for LA, such as renal disease, diabetic foot ulcer, peripheral arterial disease, pre-eclampsia, macular degeneration, or sudden sensorineural hearing loss. In these clinical settings, prospective, randomized clinical trials are therefore warranted.