{"id":"14b2afc84f94","type":"article","url":"https://hartvaat.nl/2025/05/20/plozasiran-en-lipoproteine-deeltjesgrootte-bij-hypertriglyceridemie/","title":"Plozasiran en lipoproteïne-deeltjesgrootte bij hypertriglyceridemie","title_en":"Effect of Targeting ApoC-III With Plozasiran on Lipoprotein Particle Size and Number in Hypertriglyceridemia.","category":"cholesterol","category_label":"Cholesterol","professions":["cardioloog","internist"],"tags":["dyslipidemie","ezetimibe","ldl-cholesterol","lipide-aferese","lipidenverlaging","lipoproteïne-a","lipoproteïne-a-therapeutisch-doel","niet-statine-therapie","pcsk9-remmers","pelacarsen","statines"],"journal":"Journal of the American College of Cardiology","doi":"10.1016/j.jacc.2025.03.496","source_url":"https://doi.org/10.1016/j.jacc.2025.03.496","authors":["Christie M Ballantyne","Daniel Gaudet","Robert S Rosenson","Robert A Hegele","Rong Zhou","Stacey Melquist","Jennifer Hellawell","Nicholas J Leeper"],"significance":6,"published":"2025-05-20","source_date":"2025-05-20","image":"","kennis":["https://hartvaat.nl/kennis/lipiden/inclisiran-sirna/","https://hartvaat.nl/kennis/lipiden/lipidenmedicatie-bij-ckd/"],"congress":"","summary_en":"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.","created":"2026-07-03T10:31:37Z","updated":"2026-07-03T13:30:38Z","licence":"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.","body_markdown":"Analyse toonde dat plozasiran (anti-APOC3 siRNA) niet alleen triglyceriden verlaagt maar ook de lipoproteïne-deeltjessamenstelling gunstig beïnvloedt, met minder kleine dense LDL-deeltjes.","abstract_original":"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."}