Skip to main content

Advertisement

Springer Nature Link
Log in

Lipoprotein Apheresis in the Management of Familial Hypercholesterolaemia: Historical Perspective and Recent Advances

  • New Drugs Approved for Homozygous FH (SS Virani, Section Editor)
  • Published:
Current Atherosclerosis Reports Aims and scope Submit manuscript

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. de Gennes JL, Touraine R, Maunand B, Truffert J, Laudat P. Homozygous cutaneo-tendinous forms of hypercholesteremic xanthomatosis in an exemplary familial case. Trial of plasmapheresis an heroic treatment. Bull Mem Soc Med Hôp Paris. 1967;118:1377–402.

    PubMed  Google Scholar 

  2. Turnberg LA, Mahoney MP, Gleeson MH, Freeman CB, Gowenlock AH. Plasmapheresis and plasma exchange in the treatment of hyperlipaemia and xanthomatous neuropathy in patients with primary biliary cirrhosis. Gut. 1972;13:976–81.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Thompson GR, Lowenthal R, Myant NB. Plasma exchange in the management of homozygous familial hypercholesterolaemia. Lancet. 1975;l:l208–11.

    Google Scholar 

  4. Berger GM, Miller JL, Bonnici F, Joffe HS, Dubovsky DW. Continuous flow plasma exchange in the treatment of homozygous familial hypercholesterolemia. Am J Med. 1978;65:243–51.

    Article  CAS  PubMed  Google Scholar 

  5. King ME, Breslow JL, Lees RS. Plasma-exchange therapy of homozygous familial hypercholesterolemia. N Engl J Med. 1980;302:1457–9.

    Article  CAS  PubMed  Google Scholar 

  6. Lupien PJ, Moorjani S, Awad J. A new approach to the management of familial hypercholesterolaemia: removal of plasma-cholesterol based on the principle of affinity chromatography. Lancet. 1976;1:1261–5.

    Article  CAS  PubMed  Google Scholar 

  7. Stoffel W, Borberg H, Greve V. Application of specific extracorporeal removal of low density lipoprotein in familial hypercholesterolaemia. Lancet. 1981;2:1005–7.

    Article  CAS  PubMed  Google Scholar 

  8. Thompson GR. Lipoprotein apheresis. Curr Opin Lipidol. 2010;21:487–91.

    Article  CAS  PubMed  Google Scholar 

  9. Richter WO, Jacob BG, Ritter MM, Sühler K, Vierneisel K, Schwandt P. Three-year treatment of familial heterozygous hypercholesterolemia by extracorporeal low-density lipoprotein immunoadsorption with polyclonal apolipoprotein B antibodies. Metabolism. 1993;42:888–94.

    Article  CAS  PubMed  Google Scholar 

  10. Agishi T, Kaneko I, Hasuo Y, et al. Double filtration plasmapheresis. Trans Am Soc Artif Intern Organs. 1980;26:406–11.

    CAS  PubMed  Google Scholar 

  11. Klingel R, Mausfeld P, Fassbender C, Goehlen B. Lipidfiltration—safe and effective methodology to perform lipid-apheresis. Transfus Apher Sci. 2004;30:245–54.

    Article  PubMed  Google Scholar 

  12. Yokoyama S, Hayashi R, Satani M, Yamamoto A. Selective removal of low density lipoprotein by plasma pheresis in familial hypercholesterolemia. Arteriosclerosis. 1985;5:613–22.

    Article  CAS  PubMed  Google Scholar 

  13. Mabuchi H, Michishita I, Takeda M, et al. A new low density lipoprotein apheresis system using two dextran sulfate cellulose columns in an automated column regenerating unit (LDL continuous apheresis). Atherosclerosis. 1989;68:19–26.

    Article  Google Scholar 

  14. 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. Am J Cardiol. 1992;70:1010–6.

    Article  CAS  PubMed  Google Scholar 

  15. Gordon BR, Kelsey SF, Dau PC, for the Liposorber Study Group, et al. Long-term effects of low-density lipoprotein apheresis using an automated dextran sulfate cellulose adsorption system. Am J Cardiol. 1998;81:407–11.

    Article  CAS  PubMed  Google Scholar 

  16. Eisenhauer T, Armstrong VW, Wieland H, Fuchs C, Scheler F, Seidel D. Selective removal of low density lipoproteins (LDL) by precipitation at low pH; first clinical application of the HELP system. Klin Wochenschr. 1987;65:161–8.

    Article  CAS  PubMed  Google Scholar 

  17. Armstrong VW, Windisch M, Wieland H, et al. Selective continuous extracorporeal elimination of low-density lipoproteins with heparin at acidic pH. Trans Am Soc Artif Intern Organs. 1983;29:323–8.

    CAS  PubMed  Google Scholar 

  18. Armstrong VW, Schuff-Werner P, Eisenhauer T, Helmhold M, Stix M, Seidel D. Heparin extracorporeal LDL precipitation (HELP): an effective apheresis procedure for lowering Lp(a) levels. Chem Phys Lipids. 1994;67–68:315–21.

    Article  PubMed  Google Scholar 

  19. Lane D, McConathy WJ, Laughlin LO, et al. Selective removal of plasma low density lipoprotein with the HELP system: biweekly versus weekly therapy. Atherosclerosis. 1995;114:203–11.

    Article  CAS  PubMed  Google Scholar 

  20. Bosch T, Schmidt B, Blumenstein M, Gurland HJ. Lipid apheresis by hemoperfusion: in vitro efficacy and ex vivo biocompatibility of a new low-density lipoprotein adsorber compatible with human whole blood. Artif Organs. 1993;17:640–52.

    Article  CAS  PubMed  Google Scholar 

  21. Julius U, Parhofer KG, Heibges A, Kurz S, Klingel R, Geiss HC. Dextran-sulfate-adsorption of atherosclerotic lipoproteins from whole blood or separated plasma for lipid-apheresis—comparison of performance characteristics with DALI and Lipidfiltration. J Clin Apher. 2007;22:215–23.

    Article  PubMed  Google Scholar 

  22. Thompson GR, HEART-UK LDL Apheresis Working Group. Recommendations for the use of LDL apheresis. Atherosclerosis. 2008;198:247–55.

    Article  CAS  PubMed  Google Scholar 

  23. Richter WO, Donner MG, Schwandt P. Three low density lipoprotein apheresis techniques in treatment of patients with familial hypercholesterolemia: a long-term evaluation. Ther Apher. 1999;3:203–8.

    Article  CAS  PubMed  Google Scholar 

  24. Watts GF, Hamilton SJ. LDL apheresis for familial hypercholesterolemia: value, indications and demand. Clin Lipidol. 2009;4:129–31.

    Article  Google Scholar 

  25. Stefanutti C, Lanti A, Di Giacomo S, et al. Therapeutic apheresis in low weight patients: technical feasibility, tolerance, compliance, and risks. Transfus Apher Sci. 2004;31:3–10.

    Article  CAS  PubMed  Google Scholar 

  26. Sinzingera H, Bednar J, Granegger S, Blazek I, Peskar BA. LDL-apheresis and concomitant ACE-inhibitor therapy. Atherosclerosis. 1994;105:115–6.

    Article  Google Scholar 

  27. Cashin-Hemphill L, Noone M, Abbott JF, Waksmonski CA, Lees RS. Low-density lipoprotein apheresis therapy during pregnancy. Am J Cardiol. 2000;86:1160. A10.

    Article  CAS  PubMed  Google Scholar 

  28. Goldstein JL, MS B. The LDL receptor defect in familial hypercholesterolemia. Implications for pathogenesis and therapy. Med Clin N Am. 1982;66:335–62.

    CAS  PubMed  Google Scholar 

  29. van der Westhuyzen DR, Coetzee GA, Demasius IP, Harley EH, Gevers W, Baker SG, et al. Low density lipoprotein receptor mutations in South African homozygous familial hypercholesterolemic patients. Arteriosclerosis. 1984;4:238–47.

    Article  PubMed  Google Scholar 

  30. Gautschi M, Pavlovic M, Nuoffer JM. Fatal myocardial infarction at 4.5 years in a case of homozygous familial hypercholesterolaemia. JIMD Rep. 2012;2:45–50. Describes seven cases of extremely premature mortality in FH homozygotes.

    Article  PubMed Central  PubMed  Google Scholar 

  31. Keller C. LDL-Apheresis in homozygous LDL-receptor-defective familial hypercholesterolemia: the Munich experience. Atheroscler Suppl. 2009;10:21–6.

    Article  CAS  PubMed  Google Scholar 

  32. Mabuchi H, Nohara A, Noguchi T, et al. Molecular genetic epidemiology of homozygous familial hypercholesterolemia in the Hokuriku district of Japan. Atherosclerosis. 2011;214:404–7. This paper describes the clinical and molecular characteristics of 25 FH homozygotes in the Hokuriko district of Japan, 3 of whom lived past the age of 50.

    Article  CAS  PubMed  Google Scholar 

  33. Graesdal A, Bogsrud MP, Holven KB, et al. Apheresis in homozygous familial hypercholesterolemia: the results of a follow-up of all Norwegian patients with homozygous familial hypercholesterolemia. J Clin Lipidol. 2012;6:331–9. Description of progression of cardiovascular disease in FH homozygotes in Norway despite rigorous lipoprotein apheresis and drug therapy.

    Article  PubMed  Google Scholar 

  34. Raal FJ, Pilcher GJ, Panz VR, et al. Reduction in mortality in subjects with homozygous familial hypercholesterolemia associated with advances in lipid-lowering therapy. Circulation. 2011;124:2202–7. Comparison of serum cholesterol levels and mortality in FH homozygotes in South Africa in the pre- and post-statin eras.

    Article  CAS  PubMed  Google Scholar 

  35. Thompson GR, Miller JP, Breslow JL. Improved survival of patients with homozygous familial hypercholesterolaemia treated by plasma exchange. Br Med J. 1989;291:1671–3.

    Article  Google Scholar 

  36. Thompson GR, Maher VM, Matthews S, et al. Familial hypercholesterolaemia regression study: a randomised trial of low-density-lipoprotein apheresis. Lancet. 1995;345:811–6.

    Article  CAS  PubMed  Google Scholar 

  37. Kroon AA, Aengevaeren WR, van der Werf T, LDL-Apheresis Atherosclerosis Regression Study (LAARS), et al. Effect of aggressive versus conventional lipid lowering treatment on coronary atherosclerosis. Circulation. 1996;93:1826–35.

    Article  CAS  PubMed  Google Scholar 

  38. Nishimura S, Sekiguchi M, Kano T, et al. Effects of intensive lipid lowering by low-density lipoprotein apheresis on regression of coronary atherosclerosis in patients with familial hypercholesterolemia: Japan Low-density Lipoprotein Apheresis Coronary Atherosclerosis Prospective Study (L-CAPS). Atherosclerosis. 1999;144:409–17.

    Article  CAS  PubMed  Google Scholar 

  39. Mabuchi H, Koizumi J, Shimizu M, Hokuriku-FH-LDLApheresis Study Group, et al. Long-term efficacy of low-density lipoprotein apheresis on coronary heart disease in familial hypercholesterolemia. Am J Cardiol. 1998;82:1489–95.

    Article  CAS  PubMed  Google Scholar 

  40. National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third Report of the National Cholesterol Education Program (NCEP) Expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III) final report. Circulation. 2002;106:3143–421.

    Google Scholar 

  41. Kavey R-E W, Allada V, Daniels SR, et al. Cardiovascular risk reduction in high-risk pediatric patients. A scientific statement from the american heart association expert panel on population and prevention science; the councils on cardiovascular disease in the young, epidemiology and prevention, nutrition, physical activity and metabolism, high blood pressure research, cardiovascular nursing, and the kidney in heart disease; and the interdisciplinary working group on quality of care and outcomes research. Circulation. 2006;114:2710–38.

    Article  PubMed  Google Scholar 

  42. Sczepiorkowski ZM, Bandarenko M, Kim HC, et al. Guidelines on the use of therapeutic apheresis in clinical practice—evidence-based approach from the apheresis applications committee of the American society for apheresis. J Clin Apher. 2007;22:106–75.

    Article  Google Scholar 

  43. Ito MK, McGowan MP, Moriarty PM, National Lipid Association Expert Panel on Familial Hypercholesterolemia. Management of familial hypercholesterolemias in adult patients: recommendations from the national lipid association expert panel on familial hypercholesterolemia. J Clin LipidoI. 2011;5:S38–45. US guidelines on therapeutic management of FH.

    Article  Google Scholar 

  44. Prevention of coronary heart disease in clinical practice. Recommendations of the Second Joint Task Force of European and other Societies on coronary prevention. Eur Heart J. 1998;19:1434–1503.

  45. Gemeinsamer-Bundesausschuss. Bekanntmachung eines Beschlusses des Gemeinsamen Bundesausschusses über eine Änderung der Richtlinie Methoden vertragsärztliche Versorgung: Apherese bei isolierter Lp(a)-Erhöhung für Studienteilnehmer. BAnz 2009;128:3005.

  46. Civiera F, for International Panel on Management of Familial Hypercholesterolemia. Guidelines for the diagnosis and management of heterozygous familial hypercholesterolemia. Atherosclerosis. 2004;173:55–68.

    Article  Google Scholar 

  47. Stefanutti C. The 2009 2nd Italian consensus conference on LDL-apheresis. Nutr Metab Cardiovasc Dis. 2010;20:761–2.

    Article  CAS  PubMed  Google Scholar 

  48. Harada-Shiba M, Arai H, Oikawa S, et al. Guidelines for the management of familial hypercholesterolemia. J Atheroscler Thromb. 2012;19:1043–60. Japanese guidelines on the therapeutic management of FH.

    Article  CAS  PubMed  Google Scholar 

  49. Palcoux J-B, Atassi-Dumont M, Lefevre P, et al. Low-density lipoprotein apheresis in children with familial hypercholesterolemia: follow-up to 21 years. Ther Apher Dial. 2008;12:195–201.

    Article  CAS  PubMed  Google Scholar 

  50. Hudgins L, Kleimann B, Scheuer A, White S, Gordon BR. Long-term safety and efficacy of low-density lipoprotein apheresis in childhood for homozygous familial hypercholesterolemia. Am J Cardiol. 2008;102:1199–204.

    Article  CAS  PubMed  Google Scholar 

  51. 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;102:1438–43.

    Article  PubMed  Google Scholar 

  52. Stefanutti C, Vivenzio A, Giacomo S, et al. Aorta and coronary angiographic follow-up of children with severe hypercholesterolemia treated with low-density lipoprotein apheresis. Transfusion. 2009;49:1461–70.

    Article  CAS  PubMed  Google Scholar 

  53. Nordestgaard BG, Chapman MJ, Humphries SE, et al. Familial hypercholesterolaemia 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;34:3478–90. Latest European guidelines on the therapeutic management of FH.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  54. Gagné C, Gaudet D, Bruckert E, et al. Efficacy and safety of ezetimibe coadministered with atorvastatin or simvastatin in patients with homozygous familial hypercholesterolemia. Circulation. 2002;105:2469–75.

    Article  PubMed  Google Scholar 

  55. Raal FJ, Pilcher GJ, Illingworth DR, et al. Expanded-dose simvastatin is effective in homozygous familial hypercholesterolaemia. Atherosclerosis. 1997;135249–56.

  56. Marais AD, Blom DJ, Firth JC. Statins in homozygous familial hypercholesterolemia. Curr Atheroscler Rep. 2002;4:19–25.

    Article  CAS  PubMed  Google Scholar 

  57. Naoumova RP, Thompson GR, Soutar AK. Current management of severe homozygous hypercholesterolaemias. Curr Opin Lipidol. 2004;15:413–22.

    Article  CAS  PubMed  Google Scholar 

  58. Gordon BR. Incorporation of low-density lipoprotein apheresis into the treatment program of patients with severe hypercholesterolemia. Curr Atheroscler Rep. 2000;2:308–13.

    Article  CAS  PubMed  Google Scholar 

  59. Kawaguchi A, Miyatake K, Yutani C, et al. Characteristic cardiovascular manifestation in homozygous and heterozygous familial hypercholesterolemia. Am Heart J. 1999;137:410–8.

    Article  CAS  PubMed  Google Scholar 

  60. Awan Z, Alrasadi K, Francis GA, et al. Vascular calcifications in homozygote familial hypercholesterolemia. Arterioscler Thromb Vasc Biol. 2008;28:777–85.

    Article  CAS  PubMed  Google Scholar 

  61. Bilheimer DW, Goldstein JL, Grundy SM, Starzl TE, Brown MS. Liver transplantation to provide low-density-lipoprotein receptors and lower plasma cholesterol in a child with homozygous familial hypercholesterolemia. N Engl J Med. 1984;311:1658–64.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  62. Revell SP, Noble-Jamieson G, Johnston P, Rasmussen A, Jamieson N, Barnes ND. Liver transplantation for homozygous familial hypercholesterolaemia. Arch Dis Child. 1995;73:456–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  63. Kakaei F, Nikeghbalian S, Kazemi K, et al. Liver transplantation for homozygous familial hypercholesterolemia: two case reports. Transplant Proc. 2009;41:2939–41.

    Article  CAS  PubMed  Google Scholar 

  64. Grossman M, Raper SE, Kozarsky K, et al. Successful ex vivo gene therapy directed to liver in a patient with familial hypercholesterolaemia. Nat Genet. 1994;6:335–41.

    Article  CAS  PubMed  Google Scholar 

  65. Raper SE, Grossman M, Rader DJ, et al. Safety and feasibility of liver-directed ex vivo gene therapy for homozygous familial hypercholesterolemia. Ann Surg. 1996;223:116–26.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  66. Rader DJ. Gene therapy for familial hypercholesterolemia. Nutr Metab Cardiovasc Dis. 2001;11 Suppl 5:40–4.

    PubMed  Google Scholar 

  67. Van Craeyveld E, Jacobs F, Gordts SC, De Geest B. Gene therapy for familial hypercholesterolemia. Curr Pharm Des. 2011;17:2575–91. Review on experimental LDLr gene transfer studies demonstrating regression of atherosclerosis in experimental models.

  68. Thompson GR. The evidence-base for the efficacy of lipoprotein apheresis in combating cardiovascular disease. Atheroscler Suppl. 2013;14:67–70. Latest evidence-based review on lipoprotein apheresis.

    Article  CAS  PubMed  Google Scholar 

  69. Stefanutti C, Julius U. Lipoprotein apheresis: state of the art and novelties. Atheroscler Suppl. 2013;14:19–27. Review and update on recent indications of lipoprotein apheresis and prospects of novel lipid-altering drugs for the treatment of severe dyslipidaemia.

  70. Yamamoto A, Harada-Shiba M, et al. The effect of ezetimibe on serum lipids and lipoproteins in patients with homozygous familial hypercholesterolemia undergoing LDL-apheresis therapy. Atherosclerosis. 2006;186:126–31.

    Article  CAS  PubMed  Google Scholar 

  71. Bays H, Stein EA. Pharmacotherapy for dyslipidaemia–current therapies and future agents. Expert Opin Pharmacother. 2003;4:1901–38.

    Article  CAS  PubMed  Google Scholar 

  72. Stefanutti C, Morozzi C, Di Giacomo S. New clinical perspectives of hypolipidemic drug therapy in severe hypercholesterolemia. Curr Med Chem. 2012;19:4861–8. Review and update of novel lipid-altering drugs for treatment of lipid metabolism disorders.

  73. Bell DA, Hooper AJ, Watts GF, Burnett JR. Mipomersen and other therapies for the treatment of severe familial hypercholesterolemia. Vasc Health Risk Manag. 2012;8:651–9. Recent review on mipomersen for the treatment of severe FH.

    CAS  PubMed Central  PubMed  Google Scholar 

  74. Cuchel M, Bloedon LT, Szapary PO, et al. Inhibition of microsomal triglyceride transfer protein in familial hypercholesterolemia. N Engl J Med. 2007;356:148–56.

    Article  CAS  PubMed  Google Scholar 

  75. Hooper AJ, Burnett JR. Anti-PCSK9 therapies for the treatment of hypercholesterolemia. Expert Opin Biol Ther. 2013;13:429–35. The review summarizes the latest findings in clinical trials of PCSK9 inhibitors, including antibodies, gene silencing and small peptides.

  76. Visser ME, Kastelein JJ, Stroes ES. Apolipoprotein B synthesis inhibition: results from clinical trials. Curr Opin Lipidol. 2010;21:319–23.

    Article  CAS  PubMed  Google Scholar 

  77. U.S. Food and Drug Administration. FDA approves new orphan drug for rare cholesterol disorder. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm333285.htm.

  78. U.S. Food and Drug Administration. FDA approves new orphan drug Kynamro to treat inherited cholesterol disorder. http://www.fda.gov/newsevents/newsroom/pressannouncements/ucm337195.htm.

  79. Raal FJ, Santos RD, Blom DJ, et al. Mipomersen, an apolipoprotein B synthesis inhibitor, for lowering of LDL cholesterol concentrations in patients with homozygous familial hypercholesterolaemia: a randomised, double-blind, placebo-controlled trial. Lancet. 2010;375:998–1006.

  80. 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;381:40–6. Phase 3 multicentre study on treatment of homozygous FH individuals with Lomitapide.

    Article  CAS  PubMed  Google Scholar 

  81. Stein EA, Honarpour N, Wasserman SM, Xu F, Scott R, Raal FJ. Effect of the proprotein convertase subtilisin/kexin 9 monoclonal antibody, AMG 145, in homozygous familial hypercholesterolemia. Circulation. 2013;128:2113–20. First clinical trial of PCSK9 inhibitor AMG 145 in homozygous FH subjects.

    Article  CAS  PubMed  Google Scholar 

  82. European Medicines Agency, European public assessment report (EPAR) EMA/519736/2013 EMEA/H/C/002578, pp 1–3. 18. Statement of approval of Lojuxta (lomitapide) as an adjunct to a low-fat diet and other lipid-lowering medicinal products with or without LDL-apheresis, issued by the European Commission.

  83. Roth EM, McKenney JM, Hanotin C, Asset G, Stein EA. Atorvastatin with or without an antibody to PCSK9 in primary hypercholesterolemia. N Engl J Med. 2012;367:1891–900. Randomized clinical trial involving patients with primary hypercholesterolemia, adding a PCSK9 inhibitor to either 10 mg of atorvastatin or 80 mg of atorvastatin.

  84. Nachimuthu S, Raggi P. Novel agents to manage dyslipidemias and impact atherosclerosis. Cardiovasc Hematol Disord Drug Targets. 2006;6:209–17.

    Article  CAS  PubMed  Google Scholar 

  85. Vuorio A, Tikkanen MJ, Kovanen PT. Inhibition of hepatic microsomal triglyceride transfer protein—a novel therapeutic option for treatment of homozygous familial hypercholesterolemia. Vasc Health Risk Manag. 2014;10:263–70. Review on lomitapide as novel therapeutic option for treatment of HoFH subjects.

  86. Page MM, Bell DA, Hooper AJ, Watts GF, Burnett JR. Lipoprotein apheresis and new therapies for severe familial hypercholesterolemia in adults and children. Best Pract Res Clin Endocrinol Metab. 2014;28:387–403. This review describes the rationale and role of lipoprotein apheresis in the treatment of severe FH and outlines the recent advances in pharmacotherapies for this condition.

  87. Schwartz J, Winters JL, Padmanabhan A. Guidelines on the use of therapeutic apheresis in clinical practice-evidence-based approach from the Writing Committee of the American Society for Apheresis: the sixth special issue. J Clin Apher. 2013;28:145–284. Latest guidelines on therapeutic apheresis of the American Society of Apheresis.

    Article  PubMed  Google Scholar 

Download references

Compliance with Ethics Guidelines

Conflict of Interest

Claudia Stefanutti received personal fees from Kaneka Pharma NV Europe and Aegerion.

Gilbert R. Thompson serves on the advisory board for Aegerion.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Author information

Authors and Affiliations

  1. Extracorporeal Therapeutic Techniques Unit, Lipid Clinic and Atherosclerosis Prevention Centre, Immunohematology and Transfusion Medicine, ‘Umberto I’ Hospital, Rome, Italy

    Claudia Stefanutti

  2. Department of Molecular Medicine, ‘Sapienza’ University of Rome, Rome, Italy

    Claudia Stefanutti

  3. Clinical Lipidology, Hammersmith Hospital, Imperial College London, Ducane Road, London, W12 0NN, UK

    Gilbert R. Thompson

Authors
  1. Claudia Stefanutti
    View author publications

    You can also search for this author inPubMed Google Scholar

  2. Gilbert R. Thompson
    View author publications

    You can also search for this author inPubMed Google Scholar

Corresponding author

Correspondence to Claudia Stefanutti.

Additional information

This article is part of the Topical Collection on New Drugs Approved for Homozygous FH

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Stefanutti, C., Thompson, G.R. Lipoprotein Apheresis in the Management of Familial Hypercholesterolaemia: Historical Perspective and Recent Advances. Curr Atheroscler Rep 17, 465 (2015). https://doi.org/10.1007/s11883-014-0465-6

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11883-014-0465-6

Keywords