Current insights into the German Lipoprotein Apheresis Registry (GLAR) – Almost 5 years on

Schettler, Volker; Neumann, Claas Lennart; Pristipino, Christian; Zimmermann, Thomas; Vogt, Anja; Jaeger, B.R.; Buuren, Frank van; Mellwig, Klaus-Peter; Klör, H. U.; Grützmacher, P.; Roeseler, E.; Julius, Ulrich; Heigl, Franz; Blume, Holger

doi:10.1016/j.atherosclerosissup.2017.05.006

Cited by 24 publications

(17 citation statements)

References 15 publications

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“…This observation may correspond to the recent findings derived from the German Lipoprotein Apheresis Registry (GLAR), that LA lowers the incidence rate of major adverse cardiac events and major adverse noncardiac events in patients with high LDL-C and/or high Lp(a) levels, progressive ASCVD, and who receive the maximally tolerated lipid-lowering medication (21). These observations were found to be significant after a minimum of 1 year of LA treatment (21). However, this LA-induced LDL-P reduction may additionally influence the rheology in coronary vessels and could explain the immediate improvement in coronary microvascular function (22).…”

Section: Discussionsupporting

confidence: 87%

“…Interestingly, we observe a distinct reduction of LDL‐P when LA was performed independently of the used lipid‐lowering drug regimen. This observation may correspond to the recent findings derived from the German Lipoprotein Apheresis Registry (GLAR), that LA lowers the incidence rate of major adverse cardiac events and major adverse noncardiac events in patients with high LDL‐C and/or high Lp(a) levels, progressive ASCVD, and who receive the maximally tolerated lipid‐lowering medication . These observations were found to be significant after a minimum of 1 year of LA treatment .…”

Section: Discussionsupporting

confidence: 86%

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NMR‐based lipoprotein analysis for patients with severe hypercholesterolemia undergoing lipoprotein apheresis or PCSK9‐inhibitor therapy (NAPALI‐Study)

Schettler¹,

Muellendorff²,

Schettler³

et al. 2019

Ther Apher Dial

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Taking into account the discordance between low‐density lipoprotein cholesterol (LDL‐C) and LDL particle (LDL‐P) number, cardiovascular risk more closely correlates with LDL‐P in patients. The aim of our study was to evaluate the number of lipid particles in patients with severe hypercholesterolemia treated with different lipid‐lowering regimens. Four groups of patients differing with respect to lipid‐lowering therapy were recruited from hypercholesterolemic outpatients and lipoprotein apheresis (LA) facilities, and were treated with statins alone (group A), with statins and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors (PCSK9i) (group B), with statins and LA (group C), or with statins, PCSK9i, and LA (group D). Cholesterol, triglycerides, LDL‐C, high‐density lipoprotein cholesterol (HDL‐C), LDL‐P number and size, HDL‐P number and size were determined using nuclear magnetic resonance spectroscopy. The lowest LDL‐P number was achieved at the end of LA sessions in combination with statins or in combination with statins and a monoclonal PCSK9i (median; 25th and 75th percentile) (group C: 244 nmoL/L: 237, 244, P < 0.05; group D: 244 nmoL/L: 99, 307, P < 0.05). Comparing LDL‐P number at the start of LA (group C: 978 nmoL/L: 728, 1404; group D: 954 nmoL/L: 677, 1521) to the other patient groups (groups A and B), the lowest LDL‐P number was measured in patients treated with PCSK9i and a statin (group B): LDL‐P (762 nmoL/L: 604, 1043, P < 0.05), large LDL‐P (472 nmoL/L: 296, 574, P < 0.05), and small LDL‐P (342 nmoL/L: 152, 494, P < 0.05). Very low‐density lipoprotein and HDL particle sizes remained approximately the same in all groups. LA in combination with statins or in combination with statins and PCSK9i most reduced LDL‐P numbers in hypercholesterolemic patients.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionsupporting

confidence: 86%

NMR‐based lipoprotein analysis for patients with severe hypercholesterolemia undergoing lipoprotein apheresis or PCSK9‐inhibitor therapy (NAPALI‐Study)

Schettler¹,

Muellendorff²,

Schettler³

et al. 2019

Ther Apher Dial

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“…The German Lipoprotein Apheresis Registry provides an appropriate framework to address this issue in future analyses. 33 TEAE profiles in this patient cohort, and in ODDYSSEY ESCAPE, ODYSSEY ALTERNATIVE, and GAUSS3, patients were essentially identical. However, a substantial difference was observed regarding the rates of discontinuing the application of PCSK9 antibodies due to TEAE between the real-world situation and the randomized controlled trials.…”

Section: Discussionmentioning

confidence: 57%

“…Combined treatment regimens with decreasing treatment frequency appear as the preferred choice. The German Lipoprotein Apheresis Registry provides an appropriate framework to address this issue in future analyses …”

Section: Discussionmentioning

confidence: 99%

Real‐world study: Escalating targeted lipid‐lowering treatment with PCSK9‐inhibitors and lipoprotein apheresis

Spitthöver

Röseler²,

Julius

et al. 2019

J of Clinical Apheresis

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Introduction Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition with monoclonal antibodies has complemented the armamentarium of lipid‐lowering therapy (LLT) before the final step of commencing chronic lipoprotein apheresis (LA). Data are scarce on patients who, after escalation of LLT with PCSK9 antibodies, have commenced chronic LA or PCSK9 antibody treatment during ongoing long‐term LA. Patients and Methods In this study, a cohort of 110 patients with established atherosclerotic cardiovascular disease (ASCVD) due to hypercholesterolemia or concomitant lipoprotein(a)‐hyperlipoproteinemia, who received PCSK9 antibodies for the first time during routine care, were consecutively identified. Results Mean LDL‐C concentration prior to initiation of LA or PCSK9 antibody treatment was 5.3 ± 2.6 mmol/L (205 ± 102 mg/dL). Due to established ASCVD, the risk‐adjusted LDL‐C target value was <1.8 mmol/L (<70 mg/dL) in all patients. Use of PCSK9 antibodies increased the proportion of patients attaining the LDL‐C target concentration by 41.8% overall. Treatment emergent adverse events (TEAE) associated with PCSK9 antibody medication were reported in 35 patients (31.8%). Discontinuation of PCSK9 antibody therapy due to TEAEs occurred in 25 patients (22.7%). Conclusion Finally, 55.5% of patients received a combination of PCSK9 antibody therapy and LA at individually optimized treatment frequencies resulting in an increase of target attainment in 54.1% of patients. About 18.1% of chronic LA patients terminated LA treatment in this real‐world study. The termination of long‐term LA therapy, which has hitherto prevented the progression of ASCVD, requires careful individual risk assessment and cannot be recommended by the general criteria of LDL‐C reduction.

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“…Beneficial effects of LA on the course of CVD are shown by retrospective evaluations, prospective (but not blinded, randomized controlled) trials, and analyses of the German Lipoprotein Apheresis Registry [28][29][30][31][32][33][34][35]. LA is generally well tolerated and safe [27,36] but time consuming, expensive, only offered in specialised centres, and often not covered by health insurance.…”

Section: Treatment Optionsmentioning

confidence: 99%

Lipoprotein(a)—antisense therapy

Vogt

2019

Clin Res Cardiol Suppl

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Elevated levels of lipoprotein(a) (Lp(a)) contribute to the risk of early and severe cardiovascular disease (CVD) and Lp(a) is acknowledged as a risk factor to be included in risk assessment. The established lipid-modifying medical therapies do not lower Lp(a) except niacin but no data of endpoint trials are available. Of the new lipid-modifying drugs a few have some impact on Lp(a). Whether the Lp(a) lowering effect contributes to the reduction of CVD events would have to be shown in Lp(a) dedicated trials. None of the available agents is indicated to lower Lp(a). Lipoprotein apheresis lowers levels of Lp(a) significantly by >60% per treatment. Trial data and data of the German Lipoprotein Apheresis Registry show that regular apheresis reduces cardiovascular events. The Apo(a) antisense oligonucleotide is the only approach to specifically lower Lp(a). The IONIS-APO(a)Rx phase 1 and 2 trials showed very substantial decreases of Lp(a) and good tolerability. The hepatospecific variant IONIS-APO(a)-LRx is 30 times more potent. The results of the IONIS-APO(a)-LRx phase 2 trial were presented recently. The highest dosages reduced Lp(a) by 72 and 80%; in about 81 and 98% Lp(a) levels <50 mg/dl were achieved. Tolerability and safety were confirmed, whereby injection site reactions were the most common side effects. This raises hope that the planned phase 3 trial will reproduce these findings and show a reduction of cardiovascular events.

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Current insights into the German Lipoprotein Apheresis Registry (GLAR) – Almost 5 years on

Cited by 24 publications

References 15 publications

NMR‐based lipoprotein analysis for patients with severe hypercholesterolemia undergoing lipoprotein apheresis or PCSK9‐inhibitor therapy (NAPALI‐Study)

NMR‐based lipoprotein analysis for patients with severe hypercholesterolemia undergoing lipoprotein apheresis or PCSK9‐inhibitor therapy (NAPALI‐Study)

Real‐world study: Escalating targeted lipid‐lowering treatment with PCSK9‐inhibitors and lipoprotein apheresis

Lipoprotein(a)—antisense therapy

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