Treatment with PCSK9 inhibitors induces a more anti-atherogenic HDL lipid profile in patients at high cardiovascular risk

Cécile Ingueneau (1, 2) , Tim Hollstein (3) , Thomas Grenkowitz (3) , Jean-Bernard Ruidavets (4) , Ursula Kassner (3) , Thibaut Duparc (1) , Guillaume Combes (1) , Bertrand Perret (1, 2) , Annelise Genoux (1, 2) , Friederike Schumann (3) , Thomas Bobbert (3) , Elisabeth Steinhagen-Thiessen (3) , Laurent O. Martinez (1)

1 I2MC - Institut des Maladies Métaboliques et Cardiovasculaires
2 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
3 Charité - UniversitätsMedizin = Charité - University Hospital [Berlin]
4 LEASP - Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps

Background: Proprotein Convertase Subtilisin/Kexin type 9 inhibitors (PCSK9-I) have been reported to cause a moderate increase in high-density lipoprotein (HDL) cholesterol in human studies. We thus evaluated the effect of two approved PCSK9-I on the concentration and lipid composition of HDL particle subclasses. Subjects and methods: 95 patients (62.8 ± 10.3 years old, 58% men), with or without statin and/or ezetimibe treatment and eligible for PCSK9-I therapy, received either evolocumab (140 mg) or alirocumab (75 or 150 mg). Their HDL particle profiles were measured by NMR spectroscopy at baseline and after 4 weeks of PCSK9-I treatment. Results: PCSK9-I treatment increased the level of HDL-C by 7%. The level of medium-sized HDL particles (M-HDL-P) increased (+8%) while the level of XL-HDL-P decreased (-19%). The lipid core composition was altered in the smaller S- and M-HDL-P, with a reduction in triglycerides (TG) and an enrichment in cholesterol esters (CE), whereas the for the larger XL- and L-HDL-P the relative CE content decreased and the TG content increased. Ezetimibe therapy differentially impacted the HDL particle distribution, independently of statin use, with an increase in S-HDL-P in patients not receiving ezetimibe. Conclusions: As S- and M-HDL-P levels are inversely related to cardiovascular risk, PCSK9-I treatment may result in a more atheroprotective HDL particle profile, particularly in patients not concomitantly treated with ezetimibe.

Keywords: Drug; Dyslipidemia; High-density lipoprotein; PCSK9; PSCK9 inhibition

Domains: Life Sciences [q-bio]

Cécile Ingueneau, Tim Hollstein, Thomas Grenkowitz, Jean-Bernard Ruidavets, Ursula Kassner, et al.. Treatment with PCSK9 inhibitors induces a more anti-atherogenic HDL lipid profile in patients at high cardiovascular risk. Vascular Pharmacology, 2020, 135, pp.106804 -. ⟨10.1016/j.vph.2020.106804⟩. ⟨hal-03493254⟩