Lipoprotein apheresis: From familial hypercholesterolemia and elevated lipoprotein(a) to emerging roles in peripheral arterial and renal disease

Lipoprotein apheresis (LA) achieves acute reductions of 60-80% in LDL cholesterol and lipoprotein(a) [Lp(a)] through extracorporeal removal of apolipoprotein B-containing particles, and remains the cornerstone of treatment for homozygous familial hypercholesterolemia and severe heterozygous FH refractory to pharmacotherapy. Registry data, including more than 11 years of follow-up from the German Lipoprotein Apheresis Registry, document consistent reductions in major adverse cardiovascular events across all principal indications, though randomized controlled trial evidence is absent. The introduction of PCSK9 inhibitors and inclisiran has progressively reduced apheresis utilization for LDL-centric management, while potent RNA-based Lp(a)-lowering agents (pelacarsen, olpasiran, lepodisiran) in late-stage development may further reshape the field. Beyond traditional cardiovascular indications, accumulating observational evidence supports LA in peripheral arterial disease through pleiotropic rheologic and anti-inflammatory mechanisms, and in steroid-resistant focal segmental glomerulosclerosis through oxidized LDL clearance and podocyte rescue. This review synthesizes current evidence across cardiovascular, peripheral vascular, and renal indications, compares apheresis modalities, examines integration with emerging pharmacotherapies, and proposes a three-part trajectory for LA: progressive contraction in LDL-centric use, a persisting role in Lp(a)-driven disease until RNA-based agents demonstrate outcome benefit, and a mechanistically grounded but evidence-limited niche in selected pleiotropic vascular and renal phenotypes.