# Changing from lipoprotein apheresis to evolocumab treatment lowers circulating levels of arachidonic acid and oxylipins

## TL;DR

Switching from lipoprotein apheresis to evolocumab reduces harmful fatty acids and related compounds linked to inflammation and heart disease.

## Contribution

First study comparing effects of evolocumab and lipoprotein apheresis on fatty acid and oxylipin levels in blood.

## Key findings

- Evolocumab lowers omega-6 fatty acids like arachidonic acid compared to lipoprotein apheresis.
- Evolocumab reduces arachidonic acid-derived oxylipins, which are linked to inflammation and atherosclerosis.
- Omega-3 fatty acid levels remain unchanged with evolocumab treatment.

## Abstract

Previous studies have shown that lipoprotein apheresis can modify the plasma lipidome and pro-inflammatory and pro-thrombotic lipid mediators. This has not been examined for treatment with protein convertase subtilisin/kexin type 9 inhibitors such as evolocumab, which are increasingly used instead of lipoprotein apheresis in treatment-resistant familial hypercholesterolemia. The aim of this study was to compare the effects of evolocumab treatment and lipoprotein apheresis on the fatty acid profile and on formation of lipid mediators in blood samples.

We analyzed blood samples from 37 patients receiving either lipoprotein apheresis or evolocumab treatment as part of a previous study. Patients were stratified according to receiving lipoprotein apheresis (n = 19) and evolocumab treatment (n = 18). Serum fatty acid analysis was performed using gas chromatography flame ionization detection and plasma oxylipin analysis was done using liquid chromatography tandem mass spectrometry.

Changing from lipoprotein apheresis to evolocumab treatment led to lower levels of omega-6 polyunsaturated fatty acid (n-6 PUFA) including arachidonic acid, dihomo-γ-linolenic acid and linoleic acid. Moreover, several n-6 PUFA-derived oxylipins were reduced after evolocumab treatment.

Given that arachidonic acid, either directly or as a precursor, is associated with the development of inflammation and atherosclerosis, evolocumab-mediated reductions of arachidonic acid and its metabolites might have an additional beneficial effect to lower cardiovascular risk.

•Changing from lipoprotein apheresis to evolocumab lowers blood arachidonic acid.•Omega-3 fatty acid levels were not changed by evolocumab.•Evolocumab was associated with a reduction in arachidonic acid-derived oxylipins.

Changing from lipoprotein apheresis to evolocumab lowers blood arachidonic acid.

Omega-3 fatty acid levels were not changed by evolocumab.

Evolocumab was associated with a reduction in arachidonic acid-derived oxylipins.