#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#
preLekára.sk / Journals / Athero Review / 2023 - 3

New treatment possibilities of homozygous familial hypercholesterolemia

Česká verzia

Authors: Vladimír Bláha 1;  Marta Jordánová 2;  Stanislav Zemek 3
Authors place of work: III. interní gerontometabolická klinika LF v Hradci Králové UK a FN Hradec Králové 1;  Interní oddělení Krajské nemocnice Tomáše Bati, a. s., Zlín 2;  MUDr. Nina Zemková, s. r. o., Uherské Hradiště 3
Published in the journal: AtheroRev 2023; 8(3): 177-184
Category: Reviews

Summary

Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disorder with extremely elevated low-density lipoprotein cholesterol (LDL-C) levels, and is associated with premature atherosclerotic cardiovascular disease (ACVD) in early childhood. A crucial therapeutic measure is to attempt aggressive and adequate reduction of LDL-C levels, thereby delaying the onset or manifestation of ASKVO. Therapeutic decisions are based on LDL-C levels. However, it is problematic how to achieve this goal in patients with HoFH, particularly where LDL-C levels are extremely high (often above > 10 mmol/L) or when there is an inadequate response to treatment with, for example, statins and other medications where the mechanism of action requires functional LDL receptors. Fortunately, the therapeutic options for HoFH have expanded rapidly in recent years. The mainstay is combined LDL-C lowering therapy – both pharmacological intervention and lipoprotein apheresis (LA), which additionally eliminates lipoprotein(a). Statins and ezetimibe remain the first-line drugs. The addition of new, effective therapies (i.e., subtilisin/kexin type 9 proprotein convertase inhibitors, followed by evinacumab and/or lomitapide) offers the potential to achieve LDL-C targets or reduce the need for LA. Combination therapy with bile acid sequestrants or bempedoic acid is also an option. The future of HoFH treatment, probably not too distant, will be gene therapy and gene editing using CRISPR/Cas-9 technology.

Keywords:

ANGPTL3 – ezetimibe – gene therapy – familial hypercholesterolemia –lipoprotein apheresis – lomitapide – PCSK9 inhibitors – statins

Zdroje
  1. Tromp TR, Hartgers ML, G Kees Hovingh GK et al. Worldwide experience of homozygous familial hypercholesterolaemia: retrospective cohort study. Lancet 2022; 399(10326): 719–728. Dostupné z DOI: <http://dx.doi.org/10.1016/S0140–6736(21)02001–8>.
  2. Hu P, Dharmayat KI, Stevens CA 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(22): 1742–1759. Dostupné z DOI: <http://dx.doi.org/10.1161/CIRCULATIONAHA.119.044795>.
  3. 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(9): 560–565. Dostupné z DOI: <http://dx.doi.org/10.1093/eurheartj/ehu058>.
  4. Cuchel M, Bruckert E, Ginsberg HN et al. Homozygous familial hypercholesterolaemia: new insights and guidance for clinicians to improve detection and clinical management. A position paper from the Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society. Eur Heart J 2014; 35(32): 2146–2157. Dostupné z DOI: <http://dx.doi.org/10.1093/eurheartj/ehu274>.
  5. Ference BA, Ginsberg HN, Graham I et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel. Eur Heart J 2017; 38(32): 2459–2472. Dostupné z DOI: <http://dx.doi.org/10.1093/eurheartj/ehx144>.
  6. Wiegman A, Gidding SS, Watts GF et al. Familial hypercholesterolaemia in children and adolescents: gaining decades of life by optimizing detection and treatment. Eur Heart J 2015; 36(36): 2425–2437. Dostupné z DOI: <http://dx.doi.org/10.1093/eurheartj/ehv157>.
  7. Nohara A, Tada H, Ogura M et al. Homozygous Familial Hypercholesterolemia. J Atheroscler Thromb 2021; 28(7): 665–678. Dostupné z DOI: <http://dx.doi.org/10.5551/jat.RV17050>.
  8. MillarJS, Maugeais C, Ikewaki K et al. Complete deficiency of the low-density lipoprotein receptor is associated with increased apolipoprotein B-100 production. Arterioscler Thromb Vasc Biol 2005; 25(3): 560–565. Dostupné z DOI: <http://dx.doi.org/10.1161/01.ATV.0000155323.18856.a2>.
  9. Gagné C, Gaudet D, Bruckert E. Ezetimibe Study Group Efficacy and safety of ezetimibe coadministered with atorvastatin or simvastatin in patients with homozygous familial hypercholesterolemia. Circulation 2002; 105(21): 2469–2475. Dostupné z DOI: <http://dx.doi.org/10.1161/01.cir.0000018744.58460.62>.
  10. Alder M, Bavishi A, Zumpf K et al. A Meta-Analysis Assessing Additional LDL-C Reduction from Addition of a Bile Acid Sequestrant to Statin Therapy. Am J Med 2020; 133(11): 1322–1327. Dostupné z DOI: <http://dx.doi.org/10.1016/j.amjmed.2020.03.056>.
  11. 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>.
  12. Santos RD, Stein EA, Hovingh GK et al. Long-Term Evolocumab in Patients With Familial Hypercholesterolemia. J Am Coll Cardiol 2020; 75(6): 565–574. Dostupné z DOI: <http://dx.doi.org/10.1016/j.jacc.2019.12.020>.
  13. Blom DJ, Mariko Harada-Shiba MH, Paolo Rubba P et al. Efficacy and Safety of Alirocumab in Adults With Homozygous Familial Hypercholesterolemia: The ODYSSEY HoFH Trial. J Am Coll Cardiol 2020; 76(2): 131–142. Dostupné z DOI: <http://dx.doi.org/10.1016/j.jacc.2020.05.027>.
  14. Hovingh GK, Lepor NE, Kallend D et al. Inclisiran Durably Lowers Low-Density Lipoprotein Cholesterol and Proprotein Convertase Subtilisin/Kexin Type 9 Expression in Homozygous Familial Hypercholesterolemia: The ORION-2 Pilot Study. Circulation 2020; 141(22): 1829–1831. Dostupné z DOI: <http://dx.doi.org/10.1161/CIRCULATIONAHA.119.044431>.
  15. 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/10.1186/1743–7075–9-14A>.
  16. 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>.
  17. 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>.
  18. Blom DJ, Averna MR, Meagher AW 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>.
  19. 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>-
  20. D’Erasmo L, Gallo A, Cefalù AB et al. Long-term efficacy of lipoprotein apheresis and lomitapide in the treatment of homozygous familial hypercholesterolemia (HoFH): a cross-national retrospective survey. Orphanet J Rare Dis 2021; 16(1): 381. Dostupné z DOI: <http://dx.doi.org/10.1186/s13023–021–01999–8>.
  21. 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>.
  22. Musunuru K, Pirruccello JP, Do R et al. Exome Sequencing, ANGPTL3 Mutations, and Familial Combined Hypolipidemia. N Engl J Med 2010; 363(23): 2220–2227.Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa1002926>.
  23. 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>.
  24. 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>.
  25. 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). Dostupné z DOI: <https://doi.org/10.1093/ehjci/ehaa946.3331>.
  26. 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>.
  27. Stefanutti C, Thompson GR. Lipoprotein apheresis in the management of familial hypercholesterolaemia: historical perspective and recent advances. Curr Atheroscler Rep 2015; 17(1): 465. Dostupné z DOI: <http://dx.doi.org/10.1007/s11883–014–0465–6>.
  28. Bláha V, Bláha M, Lánská M et al. Lipoprotein apheresis in the treatment of dyslipidaemia – the Czech Republic experience. Physiol Res 2017; 66(Suppl 1): S91-S100. Dostupné z DOI: <http://dx.doi.org/10.33549/physiolres.933584>.
  29. Víšek J, Bláha M, Bláha V et al. Monitoring of up to 15 years effects of lipoprotein apheresis on lipids, biomarkers of inflammation, and soluble endoglin in familial hypercholesterolemia patients. Orphanet J Rare Dis 2021; 16(1): 110. Dostupné z DOI: <http://dx.doi.org/10.1186/s13023–021–01749-w>.
  30. Thompson GR. Use of apheresis in the age of new therapies for familial hypercholesterolaemia. Curr Opin Lipidol 2021; 32(6): 363–369. Dostupné z DOI: <http://dx.doi.org/10.1097/MOL.0000000000000784>.
  31. Underberg JA, Cannon CP, Larrey D et al. Long-term safety and efficacy of lomitapide in patients with homozygous familial hypercholesterolemia: Five-year data from the Lomitapide Observational Worldwide Evaluation Registry (LOWER). J Clin Lipidol 2020; 14(6): 807–817. Dostupné z DOI: <http://dx.doi.org/10.1016/j.jacl.2020.08.006>.
  32. Ishigaki Y, Kawagishi N, Hasegawa Y et al. Liver Transplantation for Homozygous Familial Hypercholesterolemia. J Atheroscler Thromb 2019; 26(2): 121–127. Dostupné z DOI: <http://dx.doi.org/10.5551/jat.RV17029>.
  33. Martinez M, Brodlie S, Griesemer A et al. Effects of Liver Transplantation on Lipids and Cardiovascular Disease in Children With Homozygous Familial Hypercholesterolemia. Am J Cardiol 2016; 118(4): 504–510. Dostupné z DOI: <http://dx.doi.org/10.1016/j.amjcard.2016.05.042>.
  34. Kayikcioglu M, Tokgozoglu L. Current Treatment Options in Homozygous Familial Hypercholesterolemia. Pharmaceuticals (Basel) 2022; 16(1): 64. Dostupné z DOI: <http://dx.doi.org/10.3390/ph16010064>.
  35. 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>.
  36. 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>.
  37. Cuchel M, J 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/ehad19>.
Štítky
Angiology Diabetology Internal medicine Cardiology General practitioner for adults
Článek 2023 Update on European Atherosclerosis Society Consensus Statement on Homozygous Familial Hypercholesterolaemia: new treatments and clinical guidance
Článek Anti-obesity drug with exceptional benefit for preventive cardiology: current results of the SELECT trial
Článek VICTORY project: impact of complex pharmacotherapy on compensation of patients with type 2 diabetes mellitus
Článek Use of a fixed combination of ramipril with rosuvastatin in the management of lipitension: an observational study
Článek Measuring lipoprotein(a) concentrations: what and how do we measure and where do we go from here?
Článek Additional Cardiovascular Risk in Patients Living with HIV Associated with Antiretroviral Therapy
Článek Šobrův den 2023: lipidová doba postmoderní
Článek Rešerše zajímavých článků ze zahraniční literatury
Článok vyšiel v časopise

Athero Review

Číslo 3
2023 Číslo 3
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#