{"id":"90f667615125","type":"article","url":"https://hartvaat.nl/2026/12/10/pcsk9-en-apoc3-remmers-verlagen-respectievelijk-ldl-c-en-triglyceriden-meta-anal/","title":"PCSK9- en APOC3-remmers verlagen respectievelijk LDL-C en triglyceriden — meta-analyse","title_en":"Effectiveness and safety of target-specific RNA-based lipid-lowering therapies: A systematic review and meta-analysis of randomized controlled trials.","category":"cholesterol","category_label":"Cholesterol","professions":["apotheker","cardioloog","huisarts","internist"],"tags":[],"journal":"European journal of pharmacology","doi":"10.1016/j.ejphar.2026.179420","source_url":"https://doi.org/10.1016/j.ejphar.2026.179420","authors":["Jordan Steven Widjaja","Arga Setyo Adji","Aufa Baraja","Alan Dharmasaputra","Ragil Nur Rosyadi","Intan Komalasari","Ali Mustofa","Chaq El Chaq Zamzam Multazam","Firas Farisi Alkaff","Pandit Bagus Tri Saputra"],"significance":6,"published":"2026-11-05","source_date":"2026-12-10","image":"","kennis":["https://hartvaat.nl/kennis/lipiden/lpa-meten-wanneer-waarom/","https://hartvaat.nl/kennis/lipiden/ldl-cholesterol-mechanisme/"],"congress":"","summary_en":"A systematic review and meta-analysis of 16 randomized controlled trials (5,604 participants) compared target-specific RNA-based lipid-lowering therapies (inclisiran, olezarsen, plozasiran, zodasiran) against placebo in patients with hyperlipidemia or hypertriglyceridemia. PCSK9-targeted agents achieved the greatest reductions in LDL-C (-53.01%), ApoB (-39.59%), and non-HDL-C (-44.62%), whereas APOC3-targeted therapies produced the most pronounced triglyceride lowering (-52.26%). Safety profiles were comparable to placebo, though the absence of long-term clinical outcome data warrants further investigation. These findings support tailoring RNA-based lipid therapies to specific dyslipidemic phenotypes in clinical practice.","created":"2026-10-30T01:55:11Z","updated":"2026-10-30T01:55:11Z","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":"Een systematische review en meta-analyse van 16 RCT’s (5604 patiënten) vergeleek RNA-gebaseerde lipidetherapieën (inclisiran, olezarsen, plozasiran, zodasiran) met placebo bij hyperlipidemie en hypertriglyceridemie. PCSK9-remming leidde tot de grootste verlaging van LDL-C (-53,01%), ApoB (-39,59%) en non-HDL-C (-44,62%), terwijl APOC3-remming het sterkst werkte tegen triglyceriden (-52,26%). De veiligheid was vergelijkbaar met placebo, maar het ontbreken van langetermijn-uitkomstgegevens benadrukt de noodzaak van verder onderzoek. Deze data helpen bij het selecteren van de juiste therapie op basis van het lipidprofiel.","abstract_original":"RNA-based therapies target distinct pathways involved in lipid metabolism and may therefore exhibit differential pharmacological effects according to their molecular targets. However, comparative evidence regarding the effectiveness and safety of these target-specific therapies remains limited. This study aimed to evaluate the effectiveness and safety of PCSK9-, APOC3-, and ANGPTL3-targeting RNA-based therapies in patients with hyperlipidemia or hypertriglyceridemia. We conducted a systematic review and meta-analysis of randomized controlled trials comparing inclisiran, olezarsen, plozasiran, or zodasiran with placebo. Treatment effects were expressed as mean differences (MDs) or risk ratios (RRs) with 95% confidence intervals (CIs), and pooled analyses were stratified according to molecular target. Sixteen randomized controlled trials involving 5604 participants were included. PCSK9-targeting therapy produced the greatest reductions in LDL-C (MD -53.01%, 95% CI -57.56 to -48.45), ApoB (MD -39.59%, 95% CI -43.33 to -35.85), and non-HDL-C (MD -44.62%, 95% CI -47.73 to -41.51), whereas APOC3-targeting therapies produced the greatest reduction in triglycerides (MD -52.26%, 95% CI -56.50 to -48.02). Total adverse events, serious adverse events, and adverse events leading to treatment discontinuation were comparable between RNA-based therapies and placebo. Overall, these findings indicate that RNA-based lipid-lowering therapies exhibit target-specific pharmacological effects, with PCSK9 inhibition predominantly reducing atherogenic lipoproteins and APOC3 inhibition producing greater triglyceride lowering. Although the overall safety profile was comparable with placebo, differences in individual adverse outcomes and the limited availability of long-term clinical outcome data highlight the need for further investigation."}