{"id":"31fa257e4080","type":"article","url":"https://hartvaat.nl/2020/01/16/lp-a-verlaging-bij-cardiovasculaire-ziekte-nejm/","title":"Lp(a)-verlaging bij cardiovasculaire ziekte: NEJM","title_en":"Lipoprotein(a) Reduction in Persons with Cardiovascular Disease.","category":"cholesterol","category_label":"Cholesterol","professions":["apotheker","cardioloog","internist"],"tags":["ouderen"],"journal":"The New England journal of medicine","doi":"10.1056/NEJMoa1905239","source_url":"https://doi.org/10.1056/NEJMoa1905239","authors":["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"],"significance":9,"published":"2020-01-16","source_date":"2020-01-16","image":"","kennis":["https://hartvaat.nl/kennis/lipiden/lpa-meten-wanneer-waarom/","https://hartvaat.nl/kennis/lipiden/lp-a-verhoogd/"],"congress":"","summary_en":"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.","created":"2026-07-03T10:28:22Z","updated":"2026-07-03T13:27:33Z","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-studie die aantoonde dat gerichte Lp(a)-verlaging mogelijk is bij patiënten met cardiovasculaire ziekte. Bewijs dat Lp(a) een behandelbaar doelwit is.","abstract_original":"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.)."}