# Orale PCSK9-remmers: meta-analyse bevestigt krachtige LDL-daling

*geplaatst 2026-06-07 · Cholesterol · European journal of preventive cardiology · doi 10.1093/eurjpc/zwag273 · https://hartvaat.nl/2026/05/22/orale-pcsk9-remmers-meta-analyse-bevestigt-krachtige-ldl-daling/*

Een meta-analyse van vijf RCT's met drie orale PCSK9-remmers (enlicitide, NNC0385-0434 en laroprovstat; 3.295 deelnemers) toont een gepoolde LDL-C-daling van 59% ten opzichte van placebo. Ook apoB (−50%), non-HDL-cholesterol (−55%) en Lp(a) (−23%) daalden significant, zonder verhoogd risico op ernstige bijwerkingen op korte termijn. De effectiviteit van orale PCSK9-remming is daarmee vergelijkbaar met die van de injecteerbare middelen — een mogelijke doorbraak voor therapietrouw en toegankelijkheid.

## English: Efficacy and Safety of Oral PCSK9 Inhibitors: Insights from a Meta-analysis of RCTs.

A meta-analysis of five RCTs of three oral PCSK9 inhibitors (enlicitide, NNC0385-0434 and laroprovstat; 3,295 participants) shows a pooled LDL-C reduction of 59% versus placebo. ApoB (−50%), non-HDL cholesterol (−55%) and Lp(a) (−23%) also fell significantly, with no increase in short-term serious adverse events. The efficacy of oral PCSK9 inhibition is thus comparable to that of the injectable agents — a potential breakthrough for adherence and access.

## Abstract (original, from the publication)

AIM: Current proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors (the monoclonal antibodies evolocumab and alirocumab, and the siRNA inclisiran) require parenteral administration, which may limit long-term adherence. Orally active PCSK9 inhibitors could improve convenience and treatment accessibility. This meta-analysis evaluates LDL-C reduction and other lipid changes reported in randomized controlled trials (RCTs) of oral PCSK9 inhibitors. METHODS: RCTs comparing oral PCSK9 inhibitors with placebo and reporting LDL-C changes were identified through PubMed, EMBASE, Web of Science, CENTRAL, and ClinicalTrials.gov up to November 2025. Pooled mean percentage changes in lipid parameters were calculated using random- and fixed-effects models. Serious adverse events (SAEs) were analysed using risk ratios (RRs) with 95% confidence intervals (CIs). RESULTS: Five RCTs on three different molecules (enlicitide, NNC0385-0434, and laroprovstat), including a total of 3,295 participants with hypercholesterolemia receiving stable doses of background lipid-lowering therapy prior to study initiation, met the inclusion criteria. Treatment durations ranged from 8 to 24 weeks. Pooled analysis showed a significant LDL-C reduction of -59.31% (95% CI -62.33 to -56.28) compared with placebo. Additional lipid parameters also improved: apolipoprotein B (-49.53%, 95% CI -54.19 to -44.79), non-HDL cholesterol (-55.41%, 95% CI -57.35 to -53.48), and Lipoprotein(a) (-22.74%, 95% CI -26.67 to -18.81). The pooled RR for SAEs was 0.84 (95% CI 0.68-1.03; p = 0.41), indicating no increased risk versus placebo. CONCLUSIONS: Oral PCSK9 inhibitors demonstrate potent LDL-C-lowering efficacy, comparable to parenteral PCSK9i, with favourable effects on other atherogenic lipids and a reassuring short-term safety profile.

Auteurs: Elena Olmastroni, Sining Xie, Federica Galimberti, Alberico L Catapano, Manuela Casula

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Bron: European journal of preventive cardiology, https://doi.org/10.1093/eurjpc/zwag273. Bijgewerkt 2026-07-03T13:31:13Z. 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.