Efficacy of Low-Density Lipoprotein Cholesterol Apheresis in the Treatment of Familial Hypercholesterolemia: Single Center Experience

Abstract

Purpose  Familial hypercholesterolemia (FH) is a genetic disorder associated with extremely high levels of low-density lipoprotein cholesterol (LDL-C) and increased incidence of cardiovascular disease. We aimed to evaluate the efficacy and long-term outcomes of lipoprotein apheresis (LA) in the treatment of FH.

Methods  Cardiovascular events that occurred before and after LA treatment were evaluated by reviewing previous medical records of patients with FH.

Results  Thirteen patients (female/male: 8/5) were included in this study. The mean Dutch score was 20±4. All patients were treated with a combination of statin and ezetimibe. Before the onset of LA, 8 patients had a history of coronary artery disease, and the median age at onset of cardiovascular disease (CVD) in these patients was 24 years. At the initiation of LA, the median age was 22 years and the mean LDL-C level was 410±130 mg/dL. The mean duration of LA treatment was 13.9±6.9 years. The mean LDL-C levels before and after the latest three LA treatments were 267±63.4 and 71.5±23.4 mg/dL, respectively. The mean reduction in LDL-C levels after LA was 73±8.2%. De novo cardiovascular events occurred in 10 patients during LA treatment; six of these patients had a known history of CVD before LA. Eight of these patients underwent invasive procedures for therapeutic purposes and the total number of procedures was 12.

Conclusion  LA is an effective method of reducing LDL-C levels and an additional treatment option that may slow disease progression in patients with FH who are at high risk of cardiovascular events.

Keywords

Low-Density Lipoprotein Cholesterol - Apheresis - Familial Hypercholesterolemia

Publication History

Received: 02 July 2024

Accepted after revision: 29 October 2024

Article published online:
04 December 2024

• References

• 1 Benn M, Watts GF, Tybjærg-Hansen A. et al. Mutations causative of familial hypercholesterolaemia: Screening of 98 098 individuals from the Copenhagen General Population Study estimated a prevalence of 1 in 217. Eur Heart J 2016; 37: 1384-1394
• 2 Beheshti SO, Madsen CM, Varbo A. et al. Worldwide prevalence of familial hypercholesterolemia: Meta-analyses of 11 million subjects. J Am Coll Cardiol 2020; 75: 2553-2566
• 3 Hu P, Dharmayat KI, Stevens CAT. et al. Prevalence of familial hypercholesterolemia among the general population and patients with atherosclerotic cardiovascular disease: A systematic review and meta analysis. Circulation 2020; 141: 1742-1759
• 4 Sonmez A, Demirci I, Haymana C. et al. Clinical characteristics of adult and paediatric patients with familial hypercholesterolemia: A real-life cross-sectional study from the Turkish National Database. Atherosclerosis 2023; 375: 9-20
• 5 Widhalm K, Binder CB, Kreissl A. et al. Sudden death in a 4-year-old boy: A near-complete occlusion of the coronary artery caused by an aggressive low-density lipoprotein receptor mutation (W556R) in homozygous familial hypercholesterolemia. J Pediatr 2011; 158: 167
• 6 Zhang R, Xie J, Zhou J. et al. Supravalvular aortic stenosis and the risk of premature death among patients with homozygous familial hypercholesterolemia. Am J Cardiol 2021; 145: 58-63
• 7 Sjouke B, Kusters DM, Kindt I. et al. Homozygous autosomal dominant hypercholesterolaemia in the Netherlands: Prevalence, genotype-phenotype relationship, and clinical outcome. Eur Heart J 2015; 36: 560-565
• 8 Polychronopoulos G, Tzavelas M, Tziomalos K. Heterozygous familial hypercholesterolemia: prevalence and control rates. Expert Rev Endocrinol Metab 2021; 16: 175-179
• 9 Humphries SE, Cooper JA, Seed M. et al. Familial Hyperlipidaemia Register Group. Coronary heart disease mortality in treated familial hypercholesterolaemia: Update of the UK Simon Broome FH register. Atherosclerosis 2018; 274: 41-46
• 10 Mach F, Baigent C, Catapano AL. et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: Lipid modification to reduce cardiovascular risk. Eur Heart J 2020; 41: 111-188
• 11 Otto C, Geiss HC, Empen K. et al. Long-term reduction of C-reactive protein concentration by regular LDL apheresis. Atherosclerosis 2004; 174: 151-156
• 12 Stefanutti C, Thompson GR. Lipoprotein apheresis in the management of familial hypercholesterolaemia: Historical perspective and recent advances. Curr Atheroscler Rep 2015; 17: 465
• 13 Nordestgaard BG, Chapman MJ, Humphries SE. et al. European Atherosclerosis Society Consensus Panel. Familial hypercholesterolemia is underdiagnosed and undertreated in the general population: Guidance for clinicians to prevent coronary heart disease: consensus statement of the European Atherosclerosis Society. Eur Heart J 2013; 34: 3478-3490a
• 14 Grundy SM, Stone NJ, Bailey AL. et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation 2019; 139: e1082-e1143
• 15 Bouhairie VE, Goldberg AC. Familial hypercholesterolemia. Cardiol Clin 2015; 33: 169-179
• 16 Kolansky DM, Cuchel M, Clark BJ. et al. Longitudinal evaluation and assessment of cardiovascular disease in patients with homozygous familial hypercholesterolemia. Am J Cardiol 2008; 102: 1438-1443
• 17 Gordon BR, Kelsey SF, Bilheimer DW. et al. Treatment of refractory familial hypercholesterolemia by low-density lipoprotein apheresis using an automated dextran sulfate cellulose adsorption system. The Liposorber Study Group. Am J Cardiol 1992; 70: 1010-1016
• 18 Lui M, Garberich R, Strauss C. et al. Usefulness of lipid apheresis in the treatment of familial hypercholesterolemia. J Lipids 2014; 2014: 864317
• 19 Kroon AA, Aengevaeren WR, van der Werf T. et al. LDL-Apheresis Atherosclerosis Regression Study (LAARS). Effect of aggressive versus conventional lipid lowering treatment on coronary atherosclerosis. Circulation 1996; 93: 1826-1835
• 20 Banerjee S, Luo P, Reda DJ. et al. Plaque regression and endothelial progenitor cell mobilization with ıntensive lipid elimination regimen (PREMIER). Circ Cardiovasc Interv 2020; 13: e008933
• 21 Kroon AA, van’t Hof MA, Demacker PN. et al. The rebound of lipoproteins after LDL-apheresis. Kinetics and estimation of mean lipoprotein levels. Atherosclerosis 2000; 152: 519-526
• 22 Mabuchi H, Koizumi J, Shimizu M. et al. Long-term efficacy of low-density lipoprotein apheresis on coronary heart disease in familial hypercholesterolemia. American J Cardiol 1998; 82: 1489-1495
• 23 Kolovou G, Hatzigeorgiou G, Mihas C. et al. Changes in lipids and lipoproteins after selective LDL apheresis (7-year experience). Cholesterol 2012; 2012: 976578
• 24 Safarova MS, Nugent AK, Gorby L. et al. Effect of lipoprotein apheresis on progression of carotid intima-media thickness in patients with severe hypercholesterolemia. Am J Cardiol 2022; 177: 22-27
• 25 Cherepanov D, Bentley TGK, Hsiao W. et al. Real-world cardiovascular disease burden in patients with atherosclerotic cardiovascular disease: A comprehensive systematic literature review. Curr Med Res Opin 2018; 34: 459-473
• 26 Spitthöver R, Röseler T, Julius U. et al. Real-world study: Escalating targeted lipid-lowering treatment with PCSK9-inhibitors and lipoprotein apheresis. J Clin Apher 2019; 34: 423-433
• 27 Raal FJ, Stein EA, Dufour R. et al. PCSK9 inhibition with evolocumab (AMG 145) in heterozygous familial hypercholesterolaemia (RUTHERFORD-2): A randomised, double-blind, placebo-controlled trial. The Lancet 2015; 385: 331-340
• 28 Blom DJ, Fayad ZA, Kastelein JJ. et al. LOWER, a registry of lomitapide-treated patients with homozygous familial hypercholesterolemia: Rationale and design. J Clin Lipidol 2016; 10: 273-282
• 29 Cuchel M, Meagher EA, du Toit Theron H. et al. Efficacy and safety of a microsomal triglyceride transfer protein inhibitor in patients with homozygous familial hypercholesterolaemia: A single-arm, open-label, phase 3 study. Lancet 2013; 381: 40-46
• 30 Raal FJ, Rosenson RS, Reeskamp LF. et al. Evinacumab for homozygous familial hypercholesterolemia. N Engl J Med 2020; 383: 711-720
• 31 Bambauer R, Bambauer C, Lehmann B. et al. LDL-apheresis: Technical and clinical aspects. ScientificWorldJournal 2012; 2012: 314283