Elsevier

Atherosclerosis

Volume 251, August 2016, Pages 119-123
Atherosclerosis

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

https://doi.org/10.1016/j.atherosclerosis.2016.06.015Get rights and content

Highlights

  • LDL apheresis is effective in reducing LDL cholesterol and Lp(a).

  • HDL cholesterol is also reduced during LDL apheresis.

  • Switching from LDL apheresis to PCSK9 inhibition maintain the LDL lowering effect.

  • PCSK9 inhibition does not lower HDL cholesterol.

Abstract

Background and aims

LDL apheresis is effective in reducing low-density lipoprotein (LDL) cholesterol (LDL-C) and clinical endpoints, however, the treatment is invasive and time consuming. In the present study, we explored lipid profiles and quality of life in patients with heterozygous familial hypercholesterolemia (FH) when altering the treatment regimen from weekly LDL apheresis to bi-weekly evolocumab treatment.

Methods

Three patients with FH and coronary artery disease, established in LDL apheresis for 135 ± 13(SD) months, participated. The patients were examined with blood sampling before and after LDL apheresis (week 0), and before evolocumab administration (week 1–7), quality of life was assessed (week 1, 3, 7).

Results

The historically highest, untreated LDL-C was 10.3 ± 0.8 mmol/L, during weekly LDL apheresis, 5.5 ± 0.9 mmol/L pre-apheresis and 1.2 ± 0.2 mmol/L post-apheresis (p = 0.02). One week after apheresis, LDL-C was 6.1 ± 0.7 mmol/L, after three (bi-weekly) injections of evolocumab, LDL-C was 5.0 ± 0.7 (p < 0.001). High-density lipoprotein cholesterol (HDL-C) was reduced from 1.0 ± 0.2 mmol/L pre- to 0.5 ± 0.1 mmol/L post-apheresis (p = 0.03), it increased after apheresis and remained constant during evolocumab treatment. Lipoprotein(a) (Lp(a)) decreased from 484 ± 76 mg/L pre- to 142 ± 15 mg/L post-apheresis (p = 0.02), but increased during evolocumab treatment, with a small increase from week one to week seven (p < 0.01). There was a non-significant trend towards an increase in perceived health status (week 0; 57 ± 21, week three; 65 ± 9 and week seven; 77 ± 10).

Conclusions

In the current study, we demonstrate reductions in LDL-C, HDL-C, triglycerides and Lp(a) during apheresis. Switching from LDL apheresis to evolocumab maintained the LDL-lowering effect but did not decrease HDL levels.

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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