Current insights into the German lipoprotein apheresis standard: PCSK9-inhibitors, lipoprotein apheresis or both?

According to current European guidelines, lipid lowering therapy for progressive cardiovascular disease including cardiovascular events has to be focused on a target level for LDL-C. In contrast for Lp(a) a threshold has to be defined with respect to the method of measurement. However, due to new lipid lowering drug developments like PCSK9-inhibitors (PCSK-9-I) a therapeutic algorithm for patients with severe hypercholesterolemia or isolated Lipoprotein(a)-hyperlipoproteinemia with progressive cardiovascular disease may be necessary to manage the use of PCSK9-I, lipoprotein apheresis (LA) or both. The therapeutic approach for patients with homozygous familial hypercholesterolemia is unambiguous: In addition to LA, in order to improve LDL-C reduction, PCSK9-I could be applied. In patients with heterozygous familial hypercholesterolemia, PCSK9-I is to be applied first. If in addition to a pronounced LDL-C elevation, cardiovascular complications exist or if imaging techniques documented atherosclerotic changes pre-disposing for a cardiovascular event while LDL-C reduction is insufficiently reduced (LDL-C > 100 mg/dl (2.6 mmol/l)), LA treatment should then be applied as last resort. In patients with elevated Lp(a) concentrations (Lp(a) > 60 mg/dl (>120 nmol/l)) and established cardiovascular disease, therapy should rely primarily on LA methods. If in addition to high Lp(a) levels insufficiently treated LDL-C concentrations (LDL-C > 100 mg/dl (2.6 mmol/l)) exist, in rare cases PCSK9-I can supplement the lipid lowering concept.

Schettler VJJ ，Ringel J ，Jacob S ，Julius U ，Klingel R ，Heigl F ，Roeseler E ，Grützmacher P ，German Society of Nephrology (DGfN) and the Foundation of German Centers of Nephrology (DN) ... -  《-》

How effectively will PCSK9 inhibitors allow retrieval of freedom from apheresis in cardiovascular high risk patients? - Estimates form a large single center.

Lipoprotein apheresis (LA) has been the last-resort therapeutic option in patients suffering from limited pharmaceutical options to lower highly elevated low density lipoprotein cholesterol (LDL-C) levels. Facing the introduction of the proprotein convertase subtilisin/kexine type 9 (PCSK-9) inhibitors, it has been speculated that they might replace LA to a large extend. Given an efficacy of approx. 55-65% to lower LDL-C it is important to analyze whether this might be realistic i) for potential candidates in apheresis sites and ii) for the future structures of the sites themselves. We performed a review of our own single center, one of the largest apheresis centers in Germany to answer these questions. Therefore we analyzed all actively treated apheresis patients and identified those with the primary indication of LDL-C elevation. In a next step we used pre-apheresis LDL-C values to calculate expected LDL-C under three given models of PCSK9 inhibitor efficacy. Including other aspects such as the accompanying presence of elevated lipoprotein(a), we identified 11-17 patients among 29 patients undergoing treatment for insufficiently treated LDL-C (38-58%). In the total cohort of 112 patients this reflects 10-15% of all patients that might potentially stop apheresis therapy due to the availability of PCSK9 inhibitor therapy, which is in clear contrast to speculations on the future perspective of apheresis therapy.

Hohenstein B ，Tselmin S ，Bornstein SR ，Julius U ... -  《-》

Lipoprotein Apheresis and Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors in Patients With Heterozygous Familial Hypercholesterolemia: A One Center Study.

Kolovou V ，Katsiki N ，Makrygiannis S ，Mavrogieni S ，Karampetsou N ，Manolis A ，Melidonis A ，Mikhailidis DP ，Kolovou GD ... -  《-》

Statin intolerance in heterozygous familial hypercolesterolemia with cardiovascular disease: After PCSK-9 antibodies what else?

Sbrana F ，Dal Pino B ，Bigazzi F ，Ripoli A ，Passino C ，Gabutti A ，Pasanisi EM ，Petersen C ，Valleggi A ，Todiere G ，Barison A ，Giannoni A ，Panchetti L ，Becherini F ，Pianelli M ，Luciani R ，Sampietro T ... -  《-》

From lipoprotein apheresis to proprotein convertase subtilisin/kexin type 9 inhibitors: Impact on low-density lipoprotein cholesterol and C-reactive protein levels in cardiovascular disease patients.

Zenti MG ，Altomari A ，Lupo MG ，Botta M ，Bonora E ，Corsini A ，Ruscica M ，Ferri N ... -  《-》