Effectiveness of LDL Apheresis Techniques for Reducing LDL-C in Familial Hypercholesterolemia: A Systematic Review...

Familial hypercholesterolemia (FH) is a common inherited disorder characterized by markedly elevated low-density lipoprotein cholesterol (LDL-C) levels and an increased risk of premature cardiovascular disease. LDL apheresis is an extracorporeal procedure used to remove atherogenic lipoproteins from the circulation and is an established treatment option for selected patients with FH. This study aimed to systematically review and meta-analyze the effectiveness of different LDL apheresis techniques in reducing LDL-C and other lipid parameters in patients with FH.

A systematic review and meta-analysis was conducted on 9 March, 2025. PubMed/MEDLINE, Scopus, Web of Science Core Collection, EMBASE, and Google Scholar were searched using relevant keywords and Medical Subject Headings (MeSH) terms, without restrictions on publication date or publication status. Data were extracted and managed using EndNote and Microsoft Excel, and statistical analyses were performed using Stata 2017. The methodological quality of the included studies was assessed using appropriate Joanna Briggs Institute (JBI) critical appraisal checklists. Subgroup and sensitivity analyses were performed to explore potential differences according to study characteristics. Random-effects models were used to account for between-study heterogeneity.

Of 1060 records identified through database and reference-list searches, 33 studies met the inclusion criteria. Germany contributed the largest number of included studies (n = 21). The pooled mean values following LDL apheresis were 163.40 mg/dL for total cholesterol (TC; 95% CI, 135.47-191.34; I ² = 98.47%), 122.99 mg/dL for LDL-C (95% CI, 105.46-140.51; I ² = 96.71%), 19.41 mg/dL for lipoprotein(a) [Lp(a)] (95% CI, 9.84-28.98; I ² = 96.83%), and 7.06 mg/dL for high-density lipoprotein cholesterol (HDL-C) (95% CI, 5.24-8.89; I ² = 80.87%). The pooled reduction in triglycerides (TG) was 46.94 mg/dL (95% CI, 32.88-60.99; I ² = 98.47%). Among the evaluated techniques, double-filtration plasmapheresis (DFPP) showed the greatest reductions in TC, LDL-C, and HDL-C, with pooled reductions of 354.42, 281.82, and 15.75 mg/dL, respectively. No statistically significant differences among LDL apheresis techniques were observed for reductions in TG or Lp(a). Overall, the available evidence indicated reductions in these lipid parameters across the evaluated techniques, although substantial between-study heterogeneity was observed.

LDL apheresis was associated with substantial reductions in TC, LDL-C, HDL-C, TG, and Lp(a) in patients with FH. The available evidence suggests that different LDL apheresis techniques have broadly comparable effects on TG and Lp(a), whereas DFPP demonstrated greater reductions in TC, LDL-C, and HDL-C in the available comparative evidence. However, the safety evidence should be interpreted cautiously because adverse events were not quantitatively synthesized and reporting varied across studies. Therefore, the available evidence does not permit definitive conclusions regarding the comparative safety of LDL apheresis techniques. In clinical practice, selection of a specific technique should consider treatment characteristics, patient tolerance, technical requirements, resource availability, and cost considerations in addition to lipid-lowering efficacy.