Financiado en parte por Akcea Therapeutics
Lipoprotein(a) Reduction in Persons with Cardiovascular Disease
Tsimikas S, Karwatowska-Prokopczuk E, Gouni-Berthold I, Tardif JC, Baum SJ, Steinhagen-Thiessen E, Shapiro MD, Stroes ES, Moriarty PM, Nordestgaard BG, Xia S, Guerriero J, Viney NJ, O'Dea L, Witztum JL, AKCEA-APO(a)-LRx Study Investigators
The New England journal of medicine · 843 citas
Etiquetas de revisión
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Cómo se estudió
- Diseño
- Ensayo controlado aleatorizado (indexado por PubMed)
- Estudiado en
- Personas
- Resultado principal
- Marcadores de salud y funcionamiento
Quién lo pagó
- Financiación
- Financiado por la industria
- Empresa
- Akcea Therapeutics
Según 1 financiador declarado.
Publicación
- Publicado
- 2020-01-01 · N Engl J Med · vol. 382 · número 3 · págs. 244–255
- Editorial
- Massachusetts Medical Society
- Citado
- 1,076 citas · más que el 100% de estudios similares · 114.2× el promedio de su campo
- Impacto
- Entre el 10 % más citado de su campo
- Referencias
- 28 trabajos
- Acceso
- Lectura gratuita
- Áreas de investigación
- Lipoproteins and Cardiovascular Health · Lipid metabolism and disorders · Cholesterol and Lipid Metabolism
- Palabras clave
- lipoprotein(a), antisense oligonucleotides, cardiovascular disease, injection site reactions, genetic risk factors
- MeSH
- humans, cardiovascular diseases, cholesterol, lipoprotein(a), oligonucleotides, hydroxymethylglutaryl-coa reductase inhibitors, risk factors, least-squares analysis, double-blind method, dose-response relationship, drug, adult, aged, middle aged, female, male, hypolipidemic agents
15 autores
- Sotirios Tsimikas🇩🇪🇺🇸🇨🇦University of Cologne; Ionis Pharmaceuticals (United States); Montreal Heart Institute; University of California San Diego; Université de Montréal
- Ewa Karwatowska‐Prokopczuk🇩🇪🇺🇸🇨🇦University of Cologne; Ionis Pharmaceuticals (United States); Montreal Heart Institute; University of California San Diego; Université de Montréal
- Ioanna Gouni‐Berthold🇩🇪🇺🇸🇨🇦University of Cologne; Ionis Pharmaceuticals (United States); Montreal Heart Institute; University of California San Diego; Université de Montréal
- Jean‐Claude Tardif🇩🇪🇺🇸🇨🇦University of Cologne; Ionis Pharmaceuticals (United States); Montreal Heart Institute; University of California San Diego; Université de Montréal
- Seth J. Baum🇩🇪🇺🇸🇨🇦University of Cologne; Ionis Pharmaceuticals (United States); Montreal Heart Institute; University of California San Diego; Université de Montréal
- Elizabeth Steinhagen-Thiessen🇩🇪🇺🇸🇨🇦University of Cologne; Universitätsmedizin Greifswald; Ionis Pharmaceuticals (United States); Montreal Heart Institute; University of California San Diego; Universität Greifswald; Humboldt-Universität zu Berlin; Berlin Institute of Health at Charité - Universitätsmedizin Berlin; Université de Montréal; Freie Universität Berlin; Charité - Universitätsmedizin Berlin
- Michael David Shapiro🇺🇸🇩🇪🇨🇦Oregon Health & Science University; University of Cologne; Ionis Pharmaceuticals (United States); Montreal Heart Institute; University of California San Diego; Université de Montréal
- Erik S.G. Stroes🇩🇪🇺🇸🇨🇦🇳🇱University of Cologne; Ionis Pharmaceuticals (United States); Montreal Heart Institute; Amsterdam UMC Location University of Amsterdam; University of California San Diego; Université de Montréal
- Patrick M. Moriarty🇩🇪🇺🇸🇨🇦University of Cologne; Ionis Pharmaceuticals (United States); Montreal Heart Institute; University of California San Diego; University of Kansas Medical Center; Université de Montréal
- Børge Grønne Nordestgaard🇩🇰🇩🇪🇺🇸🇨🇦University of Copenhagen; University of Cologne; Ionis Pharmaceuticals (United States); Montreal Heart Institute; Herlev Hospital; Copenhagen University Hospital; Gentofte Hospital; University of California San Diego; Université de Montréal
- Shuting Xia🇩🇪🇺🇸🇨🇦University of Cologne; Ionis Pharmaceuticals (United States); Montreal Heart Institute; University of California San Diego; Université de Montréal
- Jonathan Guerriero🇩🇪🇺🇸🇨🇦University of Cologne; Ionis Pharmaceuticals (United States); Montreal Heart Institute; University of California San Diego; Université de Montréal
- Nicholas J. Viney🇩🇪🇺🇸🇨🇦University of Cologne; Ionis Pharmaceuticals (United States); Montreal Heart Institute; University of California San Diego; Université de Montréal
- Louis St L O'Dea🇩🇪🇺🇸🇨🇦University of Cologne; Ionis Pharmaceuticals (United States); Montreal Heart Institute; University of California San Diego; Université de Montréal
- Joseph Lee Witztum🇩🇪🇺🇸🇨🇦University of Cologne; Ionis Pharmaceuticals (United States); Montreal Heart Institute; University of California San Diego; Université de Montréal
Resumen
El texto original del estudio, en el idioma en que se publicó.
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 Rx 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.).
Resumen vía Europe PMC. Los derechos de autor siguen siendo de los autores o la editorial.
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