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Vascul Pharmacol. 2019 May;116:8-15. doi: 10.1016/j.vph.2019.03.002. Epub 2019 Mar 23.

Treatment with PCSK9 inhibitors reduces atherogenic VLDL remnants in a real-world study.

Author information

1
Department of Endocrinology, Campus Virchow-Klinikum, Charité Universitätsmedizin Berlin, Berlin, Germany.
2
Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, München, Germany.
3
Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
4
Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria; Department of Internal Medicine 5, Mannheim Medical Faculty, University of Heidelberg, Mannheim, Germany; Synlab Academy, Synlab Holding Germany GmbH, Mannheim, Germany.
5
Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes, Homburg, Germany; Klinik und Poliklinik für Kardiologie, Universitätsklinikum Leipzig, Leipzig, Germany.
6
Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes, Homburg, Germany.
7
Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria. Electronic address: hubert.scharnagl@medunigraz.at.

Abstract

BACKGROUND:

Proprotein convertase subtilisin-kexin type 9 inhibitors (PCSK9-I) reduce low-density lipoprotein (LDL) cholesterol in human studies. Previous studies suggest that PCSK9-I may also affect very-low-density lipoproteins (VLDL). We therefore studied VLDL size and composition in a "real-world" study population with the use of β-quantification.

SUBJECTS AND METHODS:

350 patients (62 ± 11 years old, 58% men, 22% with diabetes mellitus) with different concomitant lipid lowering therapies, and in whom PCSK9-I treatment was indicated, received either evolocumab (140 mg) or alirocumab (75 or 150 mg). The major lipoprotein fractions were separated by β-quantification and lipid and apolipoprotein compositions were determined before and 4 weeks after initiation of PCSK9-I treatment.

RESULTS:

After 4 weeks of PCSK9-I treatment, the ratio of triglycerides to apolipoprotein B in VLDL particles (VLDL-TG/apoB ratio) increased by 40% (p < .0001). VLDL-associated apolipoproteins E, CII, and CIII were reduced by 29.4%, 16.4%, and 12.4%, respectively (all p < .0001).

CONCLUSION:

PCSK9-I treatment increased VLDL size (estimated by an increased VLDL-TG/apoB ratio) and reduced VLDL-associated apolipoproteins in a heterogeneous "real-world" study-population, reflecting a higher clearance of small atherogenic VLDL remnant particles by PCSK9-I. This may potentially lower cardiovascular risk in clinical routine patients beyond low-density cholesterol (LDL-C) reduction.

KEYWORDS:

Alirocumab; Evolocumab; Lipoproteins; PCSK9 inhibitor; VLDL remnants

PMID:
30910670
DOI:
10.1016/j.vph.2019.03.002
[Indexed for MEDLINE]

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