{"id":"6d3dfde1d0df","type":"article","url":"https://hartvaat.nl/2026/05/29/rna-remmers-verlagen-lp-a-en-triglyceriden-bij-residual-risico-scoping-review/","title":"RNA-remmers verlagen Lp(a) en triglyceriden bij residual risico — scoping review","title_en":"Molecular Mechanisms and Therapeutic Targets of RNA-Based and Traditional Lipid-Lowering Agents in Residual Cardiovascular Risk: A Scoping Review of Key Directions Towards Future Perspectives.","category":"cholesterol","category_label":"Cholesterol","professions":["apotheker","cardioloog","internist"],"tags":[],"journal":"Biomolecules","doi":"10.3390/biom16060807","source_url":"https://doi.org/10.3390/biom16060807","authors":["Diana Tatarciuc","Irina Mihaela Esanu","Mioara Florentina Trandafirescu","Ana Maria Raluca Pauna","Teodor Flaviu Vasilcu","Iolanda Foia","Adina Oana Armencia","Magda Ecaterina Antohe","Dragos Catalin Ghica","Ovidiu Stamatin","Roxana Ionela Vasluianu"],"significance":5,"published":"2026-07-27","source_date":"2026-05-29","image":"","kennis":["https://hartvaat.nl/kennis/lipiden/lpa-meten-wanneer-waarom/","https://hartvaat.nl/kennis/lipiden/lipidenmedicatie-bij-ckd/"],"congress":"","summary_en":"This scoping review maps the molecular mechanisms and pharmacodynamic profiles of RNA-based lipid-lowering therapies targeting residual cardiovascular risk in patients inadequately controlled on standard care. GalNAc-conjugated siRNAs and ASOs demonstrate substantial efficacy, achieving 80–98% reductions in Lp(a), 50–80% in triglycerides, and 36–44% in LDL-C, with sustained effects every 3–6 months and a favorable safety profile. The analysis highlights how these novel agents address pathways beyond traditional statins and ezetimibe, offering clinicians a structured overview of emerging options for high-risk cardiometabolic patients.","created":"2026-07-20T01:00:46Z","updated":"2026-08-10T10:38:19Z","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":"Deze scoping review brengt de moleculaire mechanismen en klinische effecten van RNA-gebaseerde lipidumwerkers in kaart, specifiek voor patiënten met residual cardiovasculair risico ondanks standaardtherapie. siRNA’s en ASO’s leiden tot 80–98% daling van Lp(a), 50–80% daling van triglyceriden en 36–44% daling van LDL-C, met een gunstig veiligheidsprofiel en doseringsschema’s om de drie tot zes maanden. Voor cardiologen en internisten biedt dit overzicht een helder beeld van de pipeline en de farmacodynamische verschillen met traditionele lipidumwerkers, wat relevant is bij de afweging van nieuwe therapieën voor hoogrisicopatiënten.","abstract_original":"Residual cardiovascular risk arises from dysregulated expression of genes encoding apolipoprotein(a) (LPA), apolipoprotein C-III (APOC3), angiopoietin-like gene 3 (ANGPTL3), and proprotein convertase subtilisin/kexin type 9 (PCSK9). RNA-based therapies, small interfering RNAs (siRNAs), and antisense oligonucleotides (ASOs) modulate these targets at the post-transcriptional level through RNA interference and RNase H-mediated degradation, respectively. This scoping review maps the molecular mechanisms, target involvement, and pharmacodynamic outcomes of RNA therapies for managing residual cardiovascular risk, with contextual comparison to traditional lipid-lowering agents. A systematic search of PubMed, Embase, Web of Science, and Scopus was performed from 2020 to February 2026. Of the 1088 records identified, 30 studies met the inclusion criteria. RNA therapies have demonstrated potential for engagement, with 80-98% reductions in Lp(a) (pelacarsen, olpasiran, zerlasiran, lepodisiran), 50-80% reductions in triglycerides (olezarsen, plozasiran, volanesorsen), and 36-44% reductions in low-density lipoprotein cholesterol (LDL-C). Mechanistically, siRNAs achieve gene silencing through RISC-mediated mRNA cleavage, with sustained pharmacodynamic effects (3-6 months) because of Argonaute-2 stability, while gapmer ASOs recruit RNase H1 for mRNA degradation. Conjugation with GalNAc allows for hepatocyte-specific delivery with a subcutaneous bioavailability of 70-85%. Safety profiles were favorable, with injection site reactions (4-12%) being the most common adverse event. This analysis maps the emerging molecular landscape of RNA therapies, highlighting their substantial precision for targeting residual cardiovascular risk pathways that cannot be addressed by traditional agents."}