{"id":"c585698e223b","type":"article","url":"https://hartvaat.nl/2024/09/12/plozasiran-sirna-tegen-apoc3-bij-gemengde-hyperlipidemie-nejm/","title":"Plozasiran: siRNA tegen APOC3 bij gemengde hyperlipidemie — NEJM","title_en":"Plozasiran, an RNA Interference Agent Targeting APOC3, for Mixed Hyperlipidemia.","category":"cholesterol","category_label":"Cholesterol","professions":["apotheker","cardioloog","internist"],"tags":["dyslipidemie","niet-statine-therapie"],"journal":"The New England journal of medicine","doi":"10.1056/NEJMoa2404143","source_url":"https://doi.org/10.1056/NEJMoa2404143","authors":["Christie M Ballantyne","Szilard Vasas","Masoud Azizad","Peter Clifton","Robert S Rosenson","Ting Chang","Stacey Melquist","Rong Zhou","Ma'an Mushin","Nicholas J Leeper","Jennifer Hellawell","Daniel Gaudet"],"significance":9,"published":"2024-09-12","source_date":"2024-09-12","image":"","kennis":["https://hartvaat.nl/kennis/lipiden/inclisiran-sirna/","https://hartvaat.nl/kennis/lipiden/ezetimib/"],"congress":"","summary_en":"This NEJM trial of plozasiran, an RNA interference agent targeting APOC3, demonstrated dramatic triglyceride and VLDL reduction in patients with mixed hyperlipidemia. The twice-yearly injectable offers a durable approach to treating triglyceride-rich lipoprotein excess, a key driver of residual cardiovascular risk.","created":"2026-07-03T10:31:09Z","updated":"2026-07-03T13:30:11Z","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":"NEJM-trial van plozasiran bij gemengde hyperlipidemie toonde spectaculaire triglyceriden- en VLDL-verlaging. Het middel biedt een tweemaal jaarlijkse injectie die triglyceridenrijke lipoproteïnen effectief verlaagt.","abstract_original":"BACKGROUND: Persons with mixed hyperlipidemia are at risk for atherosclerotic cardiovascular disease due to an elevated non-high-density lipoprotein (HDL) cholesterol level, which is driven by remnant cholesterol in triglyceride-rich lipoproteins. The metabolism and clearance of triglyceride-rich lipoproteins are down-regulated through apolipoprotein C3 (APOC3)-mediated inhibition of lipoprotein lipase. METHODS: We carried out a 48-week, phase 2b, double-blind, randomized, placebo-controlled trial evaluating the safety and efficacy of plozasiran, a hepatocyte-targeted APOC3 small interfering RNA, in patients with mixed hyperlipidemia (i.e., a triglyceride level of 150 to 499 mg per deciliter and either a low-density lipoprotein [LDL] cholesterol level of ≥70 mg per deciliter or a non-HDL cholesterol level of ≥100 mg per deciliter). The participants were assigned in a 3:1 ratio to receive plozasiran or placebo within each of four cohorts. In the first three cohorts, the participants received a subcutaneous injection of plozasiran (10 mg, 25 mg, or 50 mg) or placebo on day 1 and at week 12 (quarterly doses). In the fourth cohort, participants received 50 mg of plozasiran or placebo on day 1 and at week 24 (half-yearly dose). The data from the participants who received placebo were pooled. The primary end point was the percent change in fasting triglyceride level at week 24. RESULTS: A total of 353 participants underwent randomization. At week 24, significant reductions in the fasting triglyceride level were observed with plozasiran, with differences, as compared with placebo, in the least-squares mean percent change from baseline of -49.8 percentage points (95% confidence interval [CI], -59.0 to -40.6) with the 10-mg-quarterly dose, -56.0 percentage points (95% CI, -65.1 to -46.8) with the 25-mg-quarterly dose, -62.4 percentage points (95% CI, -71.5 to -53.2) with the 50-mg-quarterly dose, and -44.2 percentage points (95% CI, -53.4 to -35.0) with the 50-mg-half-yearly dose (P<0.001 for all comparisons). Worsening glycemic control was observed in 10% of the participants receiving placebo, 12% of those receiving the 10-mg-quarterly dose, 7% of those receiving the 25-mg-quarterly dose, 20% of those receiving the 50-mg-quarterly dose, and 21% of those receiving the 50-mg-half-yearly dose. CONCLUSIONS: In this randomized, controlled trial involving participants with mixed hyperlipidemia, plozasiran, as compared with placebo, significantly reduced triglyceride levels at 24 weeks. A clinical outcomes trial is warranted. (Funded by Arrowhead Pharmaceuticals; MUIR ClinicalTrials.gov number NCT04998201.)."}