State of the Art: Lipoproteinapherese

Die Lipoproteinapherese (LA) ist die Ultima Ratio bei kardiovaskulären Hochrisikopatienten im Rahmen einer Sekundärprävention, nachdem Lebensstilmaßnahmen und eine maximale Pharmakotherapie das Auftreten neuer atherosklerotischer kardiovaskulärer Ereignisse nicht verhindern konnten bzw. die Zielwerte für das LDL-Cholesterin nicht erreicht wurden. In diesem Artikel werden die Studienlage, klinische praktische Erfahrungen sowie die Zukunft der LA vor dem Hintergrund der rasanten Entwicklung neuer Pharmakotherapien zusammengefasst und diskutiert.

Abstract

Lipoprotein apheresis (LA) is usually a last resort in cardiovascular high-risk patients in the context of secondary prevention after lifestyle measures and maximal pharmacotherapy have failed to prevent the occurrence of new atherosclerotic cardiovascular events (ASCVDE) or to achieve the internationally accepted target values for LDL cholesterol (LDL-C). Patients with homozygous familial hypercholesterolemia (hoFH), in whom myocardial infarctions can occur even in children < 10 years of age without adequate therapy, often owe their survival to LA (used here in primary prevention). Severe hypercholesterolemia (HCH) can often be well controlled with modern potent lipid-lowering agents, including PCSK9 approaches, so that the need for LA has decreased here over the years. In contrast, the number of patients in whom elevation of lipoprotein(a) (Lp(a)) is relevant to atherogenesis is increasing in applications to the apheresis committees of the associations of panel physicians (KV). For this indication, LA is currently the only therapeutic procedure approved by the Federal Joint Committee (G-BA). LA significantly reduces the new occurrence of ASCVDE (comparison with the situation before the start of LA), especially in Lp(a) patients. There are convincing observational studies and a German LA Registry with now 10-year data, but there is no randomized controlled trial. This had been requested by the G-BA in 2008, and a corresponding concept was designed but not accepted by the ethics committee. In addition to the highly effective reduction of atherogenic lipoproteins, many discussed pleiotropic effects of LA itself, the medical rounds and motivating discussions also with the nursing staff, which take place within the weekly LA, certainly contribute to the success of the therapy (steady adjustment of all cardiovascular risk factors, lifestyle measures including smoking cessation, adherence of medication intake). This review article summarizes and discusses the study situation, clinical practical experience as well as the future of LA against the background of the currently rapid development of new pharmacotherapies.

Kernaussagen

• Die LA ist ein gut etabliertes, sicheres und effektives Verfahren zur extrakorporalen Elimination atherogener Lipoproteine.

• Laut G-BA-Kriterien ist eine LA in Deutschland indiziert bei:

  • homozygoter FH,

  • Hochrisikopatienten mit schwerer HCH, die über 12 Monate trotz maximaler diätetischer und medikamentöser Therapie ihre LDL-C-Zielwerte nicht erreichen,

  • Lp(a)-Erhöhung ≥ 60 mg/dl (120 nmol/l) und progredienten kardiovaskulären Komplikationen, trotz möglichst optimaler Einstellung aller weiteren kardiovaskulären Risikofaktoren.

• Neben LDL-C- und Lp(a)-Senkung von mindestens 60% pro LA-Sitzung sind pleiotrope Effekte beschrieben und kardiovaskuläre Ereignisse können reduziert werden.

• Mit der Entwicklung hochpotenter Statine, Ezetimib, Bempedoinsäure und PCSK9-Ansätzen ist die Notwendigkeit der LA bei reiner Hypercholesterinämie seltener geworden, aber aufgrund sehr hoher Ausgangswerte, Unverträglichkeiten oder Kontraindikationen besteht auch hier weiterhin Bedarf.

• Am häufigsten eingesetzt wird die LA heutzutage aufgrund einer Lp(a)-Erhöhung in der Sekundärprävention.

Schlüsselwörter

Lipoproteinapherese - LDL-Cholesterin - Lipoprotein(a) - pleiotrope Effekte - kardiovaskuläre Ereignisse - lipidsenkende Pharmaka

Keywords

lipoprotein apheresis - LDL cholesterol - lipoprotein(a) - pleiotropic effects - cardiovascular events - lipid-lowering pharmaceuticals

Publication History

Article published online:
29 March 2023

• Literatur

• 1 Julius U. History of lipidology and lipoprotein apheresis. Atheroscler Suppl 2017; 30: 1-8
• 2 Thompson GR. Managing homozygous familial hypercholesterolaemia from cradle to grave. Atheroscler Suppl 2015; 18: 16-20
• 3 Kassenärztliche Bundesvereinigung. Qualitätsbericht 2021 – Berichtsjahr 2020. Accessed February 05, 2023 at: https://www.kbv.de/media/sp/KBV-Qualitaetsbericht_2021.pdf
• 4 Orsoni A, Saheb S, Levels JHM. et al. LDL-apheresis depletes apoE-HDL and pre-β1-HDL in familial hypercholesterolemia: relevance to atheroprotection. J Lipid Res 2011; 52: 2304-2313
• 5 Julius U, Frind A, Tselmin S. et al. Comparison of different LDL apheresis methods. Expert Rev Cardiovasc Ther 2008; 6: 629-639
• 6 Schettler V, de Groot K, Fassbender C. et al. Standard der therapeutischen Apherese. DGfN 2019. Accessed February 05, 2023 at: https://www.dgfn.eu/nachrichtenleser-184/standard-der-therapeutischen-apherese-2019.html
• 7 Dittrich-Riediger J, Schatz U, Hohenstein B. et al. Adverse events of lipoprotein apheresis and immunoadsorption at the Apheresis Center at the University Hospital Dresden. Atheroscler Suppl 2015; 18: 45-52
• 8 Deutsches Lipoproteinapherese-Register. Jahresbericht. 2020 Accessed February 05, 2023 at: https://www.lipid-liga.de/wp-content/uploads/2022/11/Zusammenfassung_DLAR_Jahresbericht_2020.pdf
• 9 Julius U. Lipoprotein apheresis in the management of severe hypercholesterolemia and of elevation of lipoprotein(a): current perspectives and patient selection. Med Devices (Auckl) 2016; 9: 349-360
• 10 Schettler VJJ, Schettler E. Beyond cholesterol – pleiotropic effects of lipoprotein apheresis. Ther Apher Dial 2022; 26 (Suppl. 01) 35-40
• 11 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: 1489-1495
• 12 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: 229-239
• 13 Leebmann J, Roeseler E, Julius U. et al. Lipoprotein apheresis in patients with maximally tolerated lipid-lowering therapy, lipoprotein(a)-hyperlipoproteinemia, and progressive cardiovascular disease: prospective observational multicenter study. Circulation 2013; 128: 2567-2576
• 14 Roeseler E, Julius U, Heigl F. et al. Lipoprotein Apheresis for Lipoprotein(a)-Associated Cardiovascular Disease: Prospective 5 Years of Follow-Up and Apolipoprotein(a) Characterization. Arterioscler Thromb Vasc Biol 2016; 36: 2019-2027
• 15 Dryander M, Fischer S, Passauer J. et al. Differences in the atherogenic risk of patients treated by lipoprotein apheresis according to their lipid pattern. Atheroscler Suppl 2013; 14: 39-44
• 16 Schatz U, Tselmin S, Muller 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
• 17 Julius U, Kuss S, Tselmin S. et al. Why Some Patients Undergoing Lipoprotein Apheresis Therapy Develop New Cardiovascular Events?. J Cardiovasc Dev Dis 2020; 7: 25
• 18 Schettler V, Vogt A, Julius U. et al. Das deutsche Lipoproteinaphereseregister (DLAR) – Was sind die Hintergründe?. Dialyse aktuell 2013; 17: 22-26
• 19 Khan TZ, Hsu LY, Arai AE. et al. Apheresis as novel treatment for refractory angina with raised lipoprotein(a): a randomized controlled cross-over trial. Eur Heart J 2017; 38: 1561-1569
• 20 Safarova MS, Ezhov MV, Afanasieva OI. et al. Effect of specific lipoprotein(a) apheresis on coronary atherosclerosis regression assessed by quantitative coronary angiography. Atheroscler Suppl 2013; 14: 93-99
• 21 Julius U, Schatz U, Tselmin S. et al. COVID-19 and Lipid Disorders. Horm Metab Res 2022; 54: 514-521
• 22 Thompson GR. The scientific basis and future of lipoprotein apheresis. Ther Apher Dial 2022; 26: 32-36
• 23 BfArM. Rote-Hand-Brief zu Lojuxta (Lomitapid): Überwachung der Leberfunktion und Kontraindikation während der Schwangerschaft. 17.02.2021. Accessed February 05, 2023 at: https://www.bfarm.de/SharedDocs/Risikoinformationen/Pharmakovigilanz/DE/RHB/2021/rhb-lojuxta.html