Transition from LDL apheresis to evolocumab in heterozygous FH is equally effective in lowering LDL, without lowering HDL cholesterol

Lappegård, Knut Tore; Enebakk, Terje; Thunhaug, Hilde; Hovland, Anders

doi:10.1016/j.atherosclerosis.2016.06.015

Cited by 16 publications

(18 citation statements)

References 30 publications

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“…Substantial, but transient, LDL‐C reductions can be achieved using lipoprotein apheresis in patients with HoFH, and there are data from patients with HeFH that show that switching from apheresis to evolocumab is effective in maintaining the LDL‐C‐lowering effect of apheresis . A small population of LLT‐intolerant patients with elevated LDL‐C levels may be eligible for apheresis.…”

Section: Resultsmentioning

confidence: 99%

“…Notwithstanding, German reimbursement rules currently in place require initiation of anti‐PCSK9 antibodies before approval of apheresis treatment. This is legitimate since PCSK9 inhibition may result in improved quality of life at significantly lower costs compared with apheresis . A phase 3 randomised study assessing evolocumab compared with apheresis in patients with hypercholesterolaemia who were already receiving LDL‐C apheresis is ongoing (NCT02585895).…”

Section: Resultsmentioning

confidence: 99%

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Anti-PCSK9 antibodies for hypercholesterolaemia: Overview of clinical data and implications for primary care

et al. 2017

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SummaryObjectivesTo put data from our recent systematic review of phase 3 studies of anti‐proprotein convertase subtilisin/kexin type 9 (PCSK9) antibodies into the context of clinical practice.MethodsData from studies previously identified by a systematic review of phase 3 studies of alirocumab and evolocumab and additional references from non‐systematic literature searches were used. We evaluated the hypothetical cardiovascular (CV) benefit in cases of typical patients in whom anti‐PCSK9 antibodies may be recommended, using preliminary major CV event (CVE) rates from long‐term clinical trials of anti‐PCSK9 antibodies and from extrapolations derived from correlation between low‐density lipoprotein cholesterol (LDL‐C) reduction and CV benefit with other lipid‐lowering therapies (LLTs).ResultsRapid (within 1‐2 weeks) and persistent (8‐74 weeks) reductions in LDL‐C levels were achieved with anti‐PCSK9 antibodies. When combined with statins (± ezetimibe), high rates of LDL‐C goal achievement were observed (41%‐87% with alirocumab and 63%‐100% with evolocumab). In long‐term alirocumab and evolocumab studies, reductions in major CVEs of 48% and 53%, respectively, were observed. For every 38.7 mg/dL (1 mmol/L) reduction in LDL‐C, a 22% reduction in relative CVE risk is predicted. Applying these assumptions to typical patients who have high–very high risk (15%‐60% absolute 10‐year CVE risk) and elevated LDL‐C despite maximally tolerated statins, the 10‐year number needed to treat with an anti‐PCSK9 antibody to prevent one additional CVE varies from 4 to 26, depending on baseline LDL‐C levels and residual absolute CVE risk.ConclusionsAnti‐PCSK9 antibodies effectively lower LDL‐C levels in a broad patient population. While awaiting comprehensive data from CV outcome trials, these agents should be considered in very high risk patients, such as those in secondary prevention and those with familial hypercholesterolaemia who are already receiving maximally tolerated LLTs, have not achieved their LDL‐C goal and require substantial reductions in LDL‐C.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Anti-PCSK9 antibodies for hypercholesterolaemia: Overview of clinical data and implications for primary care

et al. 2017

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“…Notably, homozygote FH patients who have minimal LDLR activity left can now be treated with PCSK9 mAbs, resulting in a ;30% decrease in circulating LDL-c . In these FH patients, switching from two to three times weekly LDL apheresis to a PCSK9 mAb combined or not with once per week LDL-c apheresis maintained the LDL-clowering effect, thereby giving a much better quality of life to these patients that is less dependent on the use of biweekly long sessions to clear LDL-c from their blood using special apheresis dialysis columns (Lappegård et al, 2016). Although the outcomes of the various ongoing phase 3 clinical trials using PCSK9 mAbs will not be known until 2017-2018 (Elbitar et al, 2016), already early signs revealed that this treatment results in a ;50% reduction in cumulative cardiovascular events within 1-2 years of treatment (Robinson et al, 2015;Sabatine et al, 2015).…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 98%

The Proprotein Convertases in Hypercholesterolemia and Cardiovascular Diseases: Emphasis on Proprotein Convertase Subtilisin/Kexin 9

et al. 2016

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The secretory proprotein convertase (PC) family comprises nine members, as follows: PC1/3, PC2, furin, PC4, PC5/6, paired basic amino acid cleaving enzyme 4, PC7, subtilisin kexin isozyme 1/site 1 protease (SKI-1/S1P), and PC subtilisin/kexin type 9 (PCSK9). The first seven PCs cleave their substrates at single/paired basic residues and exhibit specific and often essential functions during development and/or in adulthood. The essential SKI-1/S1P cleaves membrane-bound transcription factors at nonbasic residues. In contrast, PCSK9 cleaves itself once, and the secreted inactive protease drags the low-density lipoprotein receptors (LDLR) and very LDLR (VLDLR) to endosomal/lysosomal degradation. Inhibitory PCSK9 monoclonal antibodies are now prescribed to treat hypercholesterolemia. This review focuses on the implication of PCs in cardiovascular functions and diseases, with a major emphasis on PCSK9. We present a phylogeny of the PCs and the analysis of PCSK9 haplotypes in modern and archaic human species. The absence of PCSK9 in mice led to the discovery of a sex- and tissue-specific subcellular distribution of the LDLR and VLDLR. PCSK9 inhibition may have other applications because it reduces inflammation and sepsis in a LDLR-dependent manner. Our present understanding of the cellular mechanism(s) that enables PCSK9 to induce the degradation of receptors is reviewed, as well as the consequences of its key natural mutations. The PCSK9 ongoing clinical trials are reviewed. Finally, how the other PCs may impact cardiovascular disease and the metabolic syndrome, and become relevant targets, is discussed.

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“…22 The combined treatment with lipoprotein apheresis and PCSK9 inhibition has been investigated recently. 30,31 It was effective in reducing LDL-C and TG levels, while demonstrating mixed results regarding HDL-C concentration. In the current study by Zenti et al, there was a favourable effect on HDL-C level.…”

mentioning

confidence: 99%

Lipoprotein apheresis and proprotein convertase subtilisin/kexin type 9 inhibitors: Do we have a vanquishing new strategy?

Veljić

Polovina

Milinković

et al. 2018

Eur J Prev Cardiolog

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Transition from LDL apheresis to evolocumab in heterozygous FH is equally effective in lowering LDL, without lowering HDL cholesterol

Cited by 16 publications

References 30 publications

Anti-PCSK9 antibodies for hypercholesterolaemia: Overview of clinical data and implications for primary care

Anti-PCSK9 antibodies for hypercholesterolaemia: Overview of clinical data and implications for primary care

The Proprotein Convertases in Hypercholesterolemia and Cardiovascular Diseases: Emphasis on Proprotein Convertase Subtilisin/Kexin 9

Lipoprotein apheresis and proprotein convertase subtilisin/kexin type 9 inhibitors: Do we have a vanquishing new strategy?

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