# Plozasiran en lipoproteïne-deeltjesgrootte bij hypertriglyceridemie

*geplaatst 2025-05-20 · Cholesterol · Journal of the American College of Cardiology · doi 10.1016/j.jacc.2025.03.496 · https://hartvaat.nl/2025/05/20/plozasiran-en-lipoproteine-deeltjesgrootte-bij-hypertriglyceridemie/*

Analyse toonde dat plozasiran (anti-APOC3 siRNA) niet alleen triglyceriden verlaagt maar ook de lipoproteïne-deeltjessamenstelling gunstig beïnvloedt, met minder kleine dense LDL-deeltjes.

## English: Effect of Targeting ApoC-III With Plozasiran on Lipoprotein Particle Size and Number in Hypertriglyceridemia.

This analysis showed that plozasiran not only reduces triglycerides but favorably remodels the lipoprotein particle profile, shifting from small dense LDL to larger, less atherogenic particles through APOC3 suppression.

## Abstract (original, from the publication)

BACKGROUND: Plozasiran, an investigational siRNA targeting hepatic apoC-III, reduces triglyceride-rich lipoproteins (TRLs). The impact of plozasiran on lipoprotein particle numbers and sizes is unknown. However, reductions in the number of TRL particles (TRL-P) and a shift to possibly less atherogenic large low-density lipoprotein particles (LDL-P) are expected. OBJECTIVES: This study aimed to determine the impact of plozasiran on lipoprotein particle concentration and subclass distribution using nuclear magnetic resonance (NMR) in 2 phase 2 studies. METHODS: Patients (N = 403) from SHASTA-2 (severe hypertriglyceridemia) and MUIR (mixed hyperlipidemia) were administered 2 total subcutaneous doses of plozasiran (10, 25, or 50 mg) or placebo at baseline and week 12. Comprehensive lipoprotein profiling was conducted with NMR. RESULTS: In SHASTA-2, there was a dose-dependent reduction in TRL-P, with placebo-adjusted total TRL-P reductions of -46% and reductions across all TRL subclasses with plozasiran. While total LDL-P was unchanged, large LDL-P concentration increased by +53% and medium by +56%; small LDL-P trended lower (-13%). Total HDL-P increased by +8%, primarily driven by a +36% increase in large high-density lipoprotein particles (HDL-Ps). Similarly, in MUIR, there were dose-dependent reductions in TRL-P, with total TRL-P significantly reduced by -48% (pooled plozasiran) and reductions across all TRL subclasses with plozasiran. While total LDL-P was unchanged, large and medium LDL-P levels increased by +88% and +46%, respectively; small LDL-P levels decreased by -28%. Total HDL-P increased by +12%, driven by a +83% increase in large HDL-P. CONCLUSIONS: Plozasiran induced reductions in apoC-III and showed potentially favorable quantitative and qualitative changes in lipoproteins as assessed by NMR in patients with hypertriglyceridemia and mixed hyperlipidemia. Plozasiran reduced TRL-P by ∼50%, shifted LDL to larger particles, and modestly increased HDL-P concentration. While high-potency TRL-lowering therapies can lead to an overall LDL-C increase, plozasiran did not increase LDL-P or apoB but shifted LDL particle size distribution from small dense LDL toward larger sizes. The ∼50% reduction in TRL-P with no increase in apoB and possibly beneficial qualitative changes in LDL suggests the potential of plozasiran to lower cardiovascular risk, which may be evaluated in a prospective outcomes trial.

Auteurs: Christie M Ballantyne, Daniel Gaudet, Robert S Rosenson, Robert A Hegele, Rong Zhou, Stacey Melquist, Jennifer Hellawell, Nicholas J Leeper

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Bron: Journal of the American College of Cardiology, https://doi.org/10.1016/j.jacc.2025.03.496. Bijgewerkt 2026-07-03T13:30:38Z. Citeer vrij, met bronvermelding en een link naar hartvaat.nl (de url van het record). Samenvattingen zijn redactioneel werk van HartVaat; de oorspronkelijke publicaties blijven van hun uitgevers (doi). Geen medisch advies.