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The current role of lipoprotein apheresis in the context of new recommendations for hypolipidemic pharmacotherapy


Authors: Vladimír Bláha 1;  Miriam Lánská 2;  Jan Piťha 3;  Michal Vrablík 4;  Milan Bláha 2
Published in: AtheroRev 2024; 9(2): 81-91
Category: Reviews

Overview

Background: Lipoprotein apheresis (LA) is a very effective, time-consuming and costly method of lowering low-density lipoprotein cholesterol (LDL-C), lipoprotein(a) – Lp(a) and other apoB-containing lipoproteins, including triglyceride-rich lipoproteins. This method was first used almost 50 years ago and has long been a “last resort” therapy for dyslipidemias that cannot otherwise be addressed. In recent years, new, highly effective hypolipidemic agents have been developed and the purpose of this review is to define the role of lipoprotein apheresis in the current context. Discussion of the problem: Lipoprotein apheresis still plays an important role in the treatment of patients with homozygous familial hypercholesterolemia (HoFH) and some patients with other forms of hypercholesterolemia and atherosclerotic cardiovascular disease (ASCVD). In particular, patients who fail to achieve therapeutic goals despite modern hypolipidemic drug therapy, either because they are intolerant or the therapeutic response is inadequate. Lp(a) is another important cardiovascular risk factor besides LDL-C, and lipoprotein apheresis is also used to reduce lipoprotein(a) concentrations in patients with significant elevations of Lp(a) and cardiovascular disease. However, there is considerable heterogeneity in the recommendations of scientific autho­rities regarding which groups of patients should be treated with lipoprotein apheresis. Conclusion. Recommendations of professional societies indicate treatment with conventional and modern hypolipidemic agents before starting lipoprotein apheresis therapy and simultaneously with apheresis to reduce and achieve target LDL-C levels. LA does not need to precede drug therapy; on the contrary, clinical trials have shown the possibility of weaning from LA when using investigational new drugs. The combined use of lipoprotein apheresis and novel hypolipidemics (PCSK9 inhibitors, lomitapide and evinacumab) offers a valuable therapeutic approach for patients with difficult-to-control LDL-C levels. Lipoprotein apheresis remains an important tool for the treatment of patients with severe treatment-resistant dyslipidemias, especially those with homozygous FH.

Keywords:

lipoprotein apheresis – Atherosclerosis – heterozygous familial hypercholesterolemia (HeFH) – homozygous famili-al hypercholesterol­aemia (HoFH) – hypolipidemic drug therapy – cardiovascular risk –lipoprotein(a)


Sources

Duell PB, Warden BA. Complementary role of evinacumab in combination with lipoprotein apheresis in patients with homozygous familial hypercholesterolemia. Ther Apher Dial 2022; 26(Suppl 1): 12–17. Dostupné z DOI: <http://dx.doi.org/10.1111/1744–9987.13856>.

Thompson GR. The scientific basis and future of lipoprotein apheresis. Ther Apher Dial 2022; 26(1): 32–36. Dostupné z DOI: <http://dx.doi.org/10.1111/1744–9987.13716>.

Raal FJ, Honarpour N, Blom DJ et al. Inhibition of PCSK9 with evolocumab in homozygous familial hypercholesterolaemia (TESLA Part B): a randomised, double-blind, placebo-controlled trial. Lancet 2015; 385(9965): 341–350. Dostupné z DOI: <http://dx.doi.org/10.1016/S0140–6736(14)61374-X>.

Raal FJ, Rosenson RS, Reeskamp LF et al. Evinacumab for Homozygous Familial Hypercholesterolemia. N Engl J Med 2020; 383(8): 711–720. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa2004215>.

Thompson GR, Parhofer KG. Current Role of Lipoprotein Apheresis. Curr Atheroscler Rep 2019; 21(7): 26. Dostupné z DOI: <http://dx.doi.org/10.1007/s11883–019–0787–5>.

Mabuchi H, Koizumi J, Shimizu M et al. Long-term efficacy of low-density lipoprotein apheresis on coronary heart disease in familial hypercholesterolemia. Hokuriku-FH-LDL-Apheresis Study Group. Am J Cardiol 1998; 82(12):1489–1495. Dostupné z DOI: <http://dx.doi.org/10.1016/s0002–9149(98)00692–4>.

Safarova MS, Moriarty PM. Lipoprotein Apheresis: Current Recommendations for Treating Familial Hypercholesterolemia and Elevated Lipoprotein(a). Curr Atheroscler Rep 2023; 25(7): 391–404. Dostupné z DOI: <http://dx.doi.org/10.1007/s11883–023–01113–2>.

Blaha V, Bláha M, Lánská M et al. [LDL-apheresis in the treatment familial hypercholesterolemia]. Vnitr Lek 2014; 60(11): 970–976.

Julius U, Milton M, Stoellner D et al. Effects of lipoprotein apheresis on PCSK9 levels. Atheroscler Suppl 2015; 18: 180–186. Dostupné z DOI: <http://dx.doi.org/10.1016/j.atherosclerosissup.2015.02.028>.

Bláha M, Cermanová M, Blaha V et al. Safety and tolerability of long lasting LDL-apheresis in familial hyperlipoproteinemia. Ther Apher Dial 2007; 11(1): 9–15. Dostupné z DOI: <http://dx.doi.org/10.1111/j.1744–9987.2007.00450.x>.

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(10): 1826–1835. Dostupné z DOI: <http://dx.doi.org/10.1161/01.cir.93.10.1826>.

Mabuchi H, Koizumi J, Shimizu M et al. Long-term efficacy of low-density lipoprotein apheresis on coronary heart disease in familial hypercholesterolemia. Am J Cardiol 1998; 82(12): 1489–1495. Dostupné z DOI: <http://dx.doi.org/10.1016/s0002–9149(98)00692–4>.

Bambauer R, Schiel R, Latza R. Low-density lipoprotein apheresis: an overview. Ther Apher Dial 2003; 7(4): 382–390. Dostupné z DOI: <http://dx.doi.org/10.1046/j.1526–0968.2003.00070.x>.

Thompsen J, Thompson PD. A systematic review of LDL apheresis in the treatment of cardiovascular disease. Atherosclerosis 2006; 189(1): 31–38. Dostupné z DOI: <http://dx.doi.org/10.1016/j.atherosclerosis.2006.02.030>.

Moriarty PM, Gray JV, Gorby LK. Lipoprotein apheresis for lipoprotein(a) and cardiovascular disease. J Clin Lipidol 2019; 13(6): 894–900. Dostupné z DOI: <http://dx.doi.org/10.1016/j.jacl.2019.09.010>.

Gordon BR, Dau PC, Gotto jr AM et al. Long-term effects of low-density lipoprotein apheresis using an automated dextran sulfate cellulose adsorption system. Am J Cardiol 1998; 81(4): 407–411. Dostupné z DOI: <http://dx.doi.org/10.1016/s0002–9149(97)00947–8>.

Thompson GR, Lowenthal R, Myant NB. Plasma exchange in the management of homozygous familial hypercholesterolaemia. Lancet 1975; 1(7918): 1208–1211. Dostupné z DOI: <http://dx.doi.org/10.1016/s0140–6736(75)92193–5>.

Thompson GR, Miller JP, Breslow JL. Improved survival of patients with homozygous familial hypercholesterolaemia treated with plasma exchange. Br Med J (Clin Res Ed) 1985; 291(6510): 1671–1673. Dostupné z DOI: <http://dx.doi.org/10.1136/bmj.291.6510.1671>.

Thompson GR, Blom DJ, Marais AD et al. Survival in homozygous familial hypercholesterolaemia is determined by the on-treatment level of serum cholesterol. Eur Heart J 2018; 39(14): 1162–1168. Dostupné z DOI: <http://dx.doi.org/10.1093/eurheartj/ehx317>.

Thompson GR. LDL apheresis. Atherosclerosis 2003; 167(1): 1–13. Dostupné z DOI: <http://dx.doi.org/10.1016/s0021–9150(02)00251–4>.

Jaeger BR, Richter Y, Nagel D et al. Longitudinal cohort study on the effectiveness of lipid apheresis treatment to reduce high lipoprotein(a) levels and prevent major adverse coronary events. Nat Clin Pract Cardiovasc Med 2009; 6(3): 229–239. Dostupné z DOI: <http://dx.doi.org/10.1038/ncpcardio1456>.

Schatz U, Tselmin S, Müller G et al. Most significant reduction of cardiovascular events in patients undergoing lipoproteinapheresis due to raised Lp(a) levels – A multicenter observational study. Atheroscler Suppl 2017; 30: 246–252. Dostupné z DOI: <http://dx.doi.org/10.1016/j.atherosclerosissup.2017.05.047>.

Moriarty PM, Parhofer KG, Babirak SP et al. Alirocumab in patients with heterozygous familial hypercholesterolaemia undergoing lipoprotein apheresis: the ODYSSEY ESCAPE trial. Eur Heart J 2016; 37(48): 3588–3595. Dostupné z DOI: <http://dx.doi.org/10.1093/eurheartj/ehw388>.

Raal FJ, Hovingh GK, Blom D et al. Long-term treatment with evolocumab added to conventional drug therapy, with or without apheresis, in patients with homozygous familial hypercholesterolaemia: an interim subset analysis of the open-label TAUSSIG study. Lancet Diabetes Endocrinol 2017; 5(4): 280–290. Dostupné z DOI: <http://dx.doi.org/10.1016/S2213–8587(17)30044-X>.

Giammanco A, Cefalù AB, Noto D et al. Therapeutic Options for Homozygous Familial Hypercholesterolemia: The Role of Lomitapide. Curr Med Chem 2020; 27(23): 3773–3783. Dostupné z DOI: <http://dx.doi.org/10.2174/0929867326666190121120735>.

Hussain MM, Rava P, Walsh M et al. Multiple functions of microsomal triglyceride transfer protein. Nutr Metab (Lond) 2012; 9(1): 14. Dostupné z DOI: <http://dx.doi.org/10.1186/1743–7075–9-14>.

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(9860): 40–46. Dostupné z DOI: <http://dx.doi.org/10.1016/S0140–6736(12)61731–0>.

Nohara A, Otsubo Y, Yanagi K et al. Safety and Efficacy of Lomitapide in Japanese Patients with Homozygous Familial Hypercholesterolemia (HoFH): Results from the AEGR-733–301 Long-Term Extension Study. J Atheroscler Thromb 2019; 26(4): 368–377. Dostupné z DOI: <http://dx.doi.org/10.5551/jat.45708>.

Blom DJ, Averna MR, Meagher EA et al. Long-Term Efficacy and Safety of the Microsomal Triglyceride Transfer Protein Inhibitor Lomitapide in Patients With Homozygous Familial Hypercholesterolemia. Circulation 2017; 136(3): 332–335. Dostupné z DOI: <http://dx.doi.org/10.1161/CIRCULATIONAHA.117.028208>.

D’Erasmo L, Steward K, Cefalù AB et al. Efficacy and safety of lomitapide in homozygous familial hypercholesterolaemia: the pan-European retrospective observational study. Eur J Prev Cardiol 2022; 29(5): 832–841. Dostupné z DOI: <http://dx.doi.org/10.1093/eurjpc/zwab229>.

Stefanutti C, Blom DJ, Averna MR et al. The lipid-lowering effects of lomitapide are unaffected by adjunctive apheresis in patients with homozygous familial hypercholesterolaemia – a post-hoc analysis of a Phase 3, single-arm, open-label trial. Atherosclerosis 2015; 240(2): 408–414. Dostupné z DOI: <http://dx.doi.org/10.1016/j.atherosclerosis.2015.03.014>.

Larrey D, D’Erasmo L, O’Brien S et al. Long-term hepatic safety of lomitapide in homozygous familial hypercholesterolaemia. Liver Int 2023; 43(2): 413–423. Dostupné z DOI: <http://dx.doi.org/10.1111/liv.15497>.

Stefanutti C. Lomitapide – a Microsomal Triglyceride Transfer Protein Inhibitor for Homozygous Familial Hypercholesterolemia. Curr Atheroscler Rep 2020; 22(8): 38. Dostupné z DOI: <http://dx.doi.org/10.1007/s11883–020–00858–4>.

Parhofer KG. New approaches to address dyslipidemia. Curr Opin Lipidol 2017; 28(6): 452–457. Dostupné z DOI: <http://dx.doi.org/10.1097/MOL.0000000000000456>.

Warden BA, Duell PB. Evinacumab for treatment of familial hypercholesterolemia. Expert Rev Cardiovasc Ther 2021;19(8):739–751. Dostupné z DOI: <http://dx.doi.org/10.1080/14779072.2021.1955349>.

Musunuru K, Pirruccello JP, Do R et al. Exome Sequencing, ANGPTL3 Mutations, and Familial Combined Hypolipidemia. N Eng J Med 2010; 363(23): 2220–2227. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa1002926>.

Dewey FE, Gusarova V, Dunbar RL et al. Genetic and Pharmacologic Inactivation of ANGPTL3 and Cardiovascular Disease. N Engl J Med 2017; 377(3): 211–221. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa1612790>.

Béliard S, Saheb S, Litzler-Renault S et al. Evinacumab and Cardiovascular Outcome in Patients with Homozygous Familial Hypercholesterolemia. Arterioscler Thromb Vasc Biol 2024; 44(6): 1447–1454. Dostupné z DOI: <http://dx.doi.org/10.1161/ATVBAHA.123.320609>.

Raal FJ, Rosenson RS, Reeskamp LF et al. The Long-Term Efficacy and Safety of Evinacumab in Patients With Homozygous Familial Hypercholesterolemia. JACC Adv 2023; 2(9): 100648. Dostupné z DOI: <http://dx.doi.org/10.1016/j.jacadv.2023.100648>.

Watts GF, Schwabe C, Scott R et al. RNAi inhibition of angiopoietin-like protein 3 (ANGPTL3) with ARO-ANG3 mimics the lipid and lipoprotein profile of familial combined hypolipidemia. Eur Heart J 2020; 41(Suppl 2): ehaa946.3331. Dostupné z DOI: <http://dx.doi.org/10.1093/ehjci/ehaa946.3331>.

Graham MJ, Lee RG, Brandt TA et al. Cardiovascular and Metabolic Effects of ANGPTL3 Antisense Oligonucleotides. N Engl J Med 2017; 377(3): 222–232.Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa1701329>.

Tsimikas S, Viney NJ, Hughes SG et al. Antisense therapy targeting apolipoprotein(a): a randomised, double-blind, placebo-controlled phase 1 study. Lancet 2015; 386(10002): 1472–1483. Dostupné z DOI: <http://dx.doi.org/10.1016/S0140–6736(15)61252–1>.

Cuchel M, Raal FJ, Hegele RA et al. 2023 Update on European Atherosclerosis Society Consensus Statement on Homozygous Familial Hypercholesterolaemia: new treatments and clinical guidance. Eur Heart J 2023; 44(25): 2277–2291. Dostupné z DOI: <http://dx.doi.org/10.1093/eurheartj/ehad197>.

Kayikcioglu M, Tokgozoglu L. Current Treatment Options in Homozygous Familial Hypercholesterolemia. Pharmaceuticals (Basel) 2023; 16(1): 64. Dostupné z DOI: <http://dx.doi.org/10.3390/ph16010064>.

Chadwick AC, Evitt NH, Lv W et al. Reduced Blood Lipid Levels With In Vivo CRISPR-Cas9 Base Editing of ANGPTL3. Circulation 2018; 137(9): 975–977.Dostupné z DOI: <http://dx.doi.org/10.1161/CIRCULATIONAHA.117.031335>.

Musunuru K, Chadwick AC, Mizoguchi T et al. In vivo CRISPR base editing of PCSK9 durably lowers cholesterol in primates. Nature 2021; 593(7859): 429–434. Dostupné z DOI: <http://dx.doi.org/10.1038/s41586–021–03534-y>.

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