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

Hollstein, Tim; Vogt, Anja; Grenkowitz, Thomas; Stojakovic, Tatjana; Maerz, Winfried; Laufs, Ulrich; Boeluekbasi, Bediha; Steinhagen-Thiessen, Elisabeth; Scharnagl, Hubert und Kassner, Ursula (2019): Treatment with PCSK9 inhibitors reduces atherogenic VLDL remnants in a real-world study. In: Vascular Pharmacology, Bd. 116: S. 8-15

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 beta-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 beta-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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1537-1891
• Sprache: Englisch