Transition from LDL apheresis to evolocumab in heterozygous FH is equally effective in lowering LDL, without lowering HDL cholesterol
Introduction
Heterozygous familial hypercholesterolemia (FH) is an autosomal dominant disease with a prevalence of 0.2–0.5% that, due to high levels of low-density lipoprotein (LDL) cholesterol, carries a high risk of premature atherosclerosis [1]. Statins have been a game changer in treating patients with elevated levels of LDL cholesterol [2]. Some patients, however, experience side effects from statins, most commonly muscle pain, and hence must stop the medication [3].
When FH is not adequately controlled with medication, extracorporeal treatment by means of LDL apheresis has been the preferred treatment. This treatment is highly effective in reducing both LDL cholesterol and clinical endpoints [4]. In addition to lowering LDL cholesterol, LDL apheresis also effectively lowers Lp(a) [5], a lipoprotein increasing the risk of cardiovascular endpoints in FH patients [6]. An unwanted lipoprotein effect of LDL apheresis is the lowering of high density lipoprotein (HDL) cholesterol [4]. As the treatment is invasive and time consuming, some patients report side effects and reduced quality of life [7], [8].
The new proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are effective in reducing LDL cholesterol (50–60%) and Lp(a) (20%) [9]. PCSK9 inhibitors exert their effect by increasing the LDL receptor function due to decreased degradation, however more complex interactions between PCSK9, LDL receptors and levels of lipoproteins exist [10], and all of PCSK9’s physiological properties are yet to be discovered [11]. Clinical endpoints studies are being performed, possibly with results in 2016 or 2017. Currently, among PCSK9 inhibitors, the monoclonal antibodies evolocumab and alirocumab are available for clinical use, they are both effective and well tolerated [12], [13].
In the present study, we explored lipid profiles and quality of life in patients with heterozygous FH established in long term LDL apheresis when altering the treatment regimen from weekly LDL apheresis to bi-weekly subcutaneous evolocumab treatment.
Section snippets
Materials and methods
The study was designed as an observational study with three FH patients established in long-term LDL apheresis. Treatment was converted to a PCSK9 inhibitor (evolocumab), and the patients were examined immediately before and after their last apheresis treatment (week 0), after one week (immediately before the first evolocumab injection (week 1)), then biweekly before administration of evolocumab (weeks 3, 5 and 7) (Fig. 1).
Lipid profiles, untreated vs. week 0 to seven
Historically high, untreated LDL cholesterol was 10.3 ± 0.8 mmol/L. There was a significant reduction in LDL cholesterol from 5.5 ± 0.9 mmol/L pre-apheresis (this value reflecting long time LDL apheresis) to 1.2 ± 0.2 mmol/L post-apheresis (p = 0.02), week 0. As expected, LDL cholesterol increased at week one, before the first injection of evolocumab. There was a significant decrease in LDL cholesterol from 6.1 ± 0.7 mmol/L at week one to 5.0 ± 0.7 mmol/L at week seven (p < 0.001), after three
Discussion
In the current study, we demonstrate anticipated reductions in lipoproteins during LDL apheresis. Furthermore when switching from LDL apheresis to the PCSK9 inhibitor evolocumab, the LDL cholesterol levels are about 50% lower than historically high, untreated values. The pre-apheresis LDL value reflects long time apheresis treatment, and there is a small, but significant decrease in LDL from week one to week seven after three consecutive treatments with evolocumab. HDL cholesterol levels were
Conflict of interest
The authors declared that they do not have anything to disclose regarding conflict of interest with respect to this manuscript.
Financial support
The research group has received financial support from Amgen.
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Lipoprotein apheresis affects lipoprotein particle subclasses more efficiently compared to the PCSK9 inhibitor evolocumab, a pilot study
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