# Lp(a)-verlaging bij cardiovasculaire ziekte: NEJM

*geplaatst 2020-01-16 · Cholesterol · The New England journal of medicine · doi 10.1056/NEJMoa1905239 · https://hartvaat.nl/2020/01/16/lp-a-verlaging-bij-cardiovasculaire-ziekte-nejm/*

NEJM-studie die aantoonde dat gerichte Lp(a)-verlaging mogelijk is bij patiënten met cardiovasculaire ziekte. Bewijs dat Lp(a) een behandelbaar doelwit is.

## English: Lipoprotein(a) Reduction in Persons with Cardiovascular Disease.

This NEJM study demonstrated proof-of-concept that targeted lipoprotein(a) reduction is achievable in patients with established cardiovascular disease using an antisense oligonucleotide. The results validated Lp(a) as a druggable target and paved the way for the large-scale cardiovascular outcomes trials now underway.

## Abstract (original, from the publication)

BACKGROUND: Lipoprotein(a) levels are genetically determined and, when elevated, are a risk factor for cardiovascular disease and aortic stenosis. There are no approved pharmacologic therapies to lower lipoprotein(a) levels. METHODS: We conducted a randomized, double-blind, placebo-controlled, dose-ranging trial involving 286 patients with established cardiovascular disease and screening lipoprotein(a) levels of at least 60 mg per deciliter (150 nmol per liter). Patients received the hepatocyte-directed antisense oligonucleotide AKCEA-APO(a)-LRx, referred to here as APO(a)-LRx (20, 40, or 60 mg every 4 weeks; 20 mg every 2 weeks; or 20 mg every week), or saline placebo subcutaneously for 6 to 12 months. The lipoprotein(a) level was measured with an isoform-independent assay. The primary end point was the percent change in lipoprotein(a) level from baseline to month 6 of exposure (week 25 in the groups that received monthly doses and week 27 in the groups that received more frequent doses). RESULTS: The median baseline lipoprotein(a) levels in the six groups ranged from 204.5 to 246.6 nmol per liter. Administration of APO(a)-LRx resulted in dose-dependent decreases in lipoprotein(a) levels, with mean percent decreases of 35% at a dose of 20 mg every 4 weeks, 56% at 40 mg every 4 weeks, 58% at 20 mg every 2 weeks, 72% at 60 mg every 4 weeks, and 80% at 20 mg every week, as compared with 6% with placebo (P values for the comparison with placebo ranged from 0.003 to <0.001). There were no significant differences between any APO(a)-LRx dose and placebo with respect to platelet counts, liver and renal measures, or influenza-like symptoms. The most common adverse events were injection-site reactions. CONCLUSIONS: APO(a)-LRx reduced lipoprotein(a) levels in a dose-dependent manner in patients who had elevated lipoprotein(a) levels and established cardiovascular disease. (Funded by Akcea Therapeutics; ClinicalTrials.gov number, NCT03070782.).

Auteurs: Sotirios Tsimikas, Ewa Karwatowska-Prokopczuk, Ioanna Gouni-Berthold, Jean-Claude Tardif, Seth J Baum, Elizabeth Steinhagen-Thiessen, Michael D Shapiro, Erik S Stroes, Patrick M Moriarty, Børge G Nordestgaard, Shuting Xia, Jonathan Guerriero, Nicholas J Viney, Louis O'Dea, Joseph L Witztum

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Bron: The New England journal of medicine, https://doi.org/10.1056/NEJMoa1905239. Bijgewerkt 2026-07-03T13:27:33Z. 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.