Financiado en parte por Amgen
Small Interfering RNA to Reduce Lipoprotein(a) in Cardiovascular Disease
O'Donoghue ML, Rosenson RS, Gencer B, López JAG, Lepor NE, Baum SJ, Stout E, Gaudet D, Knusel B, Kuder JF, Ran X, Murphy SA, Wang H, Wu Y, Kassahun H, Sabatine MS, OCEAN(a)-DOSE Trial Investigators
The New England journal of medicine · 479 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
- Amgen
- Gobierno
- Japan Society for the Promotion of Science
- Subvenciones
- Japan Society for the Promotion of Science (21K08139); Japan Society for the Promotion of Science (18K08051)
Según 2 financiadores declarados.
Publicación
- Publicado
- 2022-11-06 · N Engl J Med · vol. 387 · número 20 · págs. 1855–1864
- Editorial
- Massachusetts Medical Society
- Citado
- 601 citas · más que el 100% de estudios similares · 88.9× el promedio de su campo
- Impacto
- Entre el 10 % más citado de su campo
- Referencias
- 24 trabajos
- Acceso
- Lectura gratuita
- Áreas de investigación
- Lipoproteins and Cardiovascular Health · Lipid metabolism and disorders · Atherosclerosis and Cardiovascular Diseases
- Palabras clave
- olpasiran, lipoprotein(a), siRNA, atherosclerotic cardiovascular disease, PCSK9, cardiovascular risk reduction, injection site reactions, LDL cholesterol, statin therapy, ezetimibe, PCSK9 inhibitors, safety and tolerability
- MeSH
- liver, humans, cardiovascular diseases, hypercholesterolemia, lipoprotein(a), rna, small interfering, anticholesteremic agents, hydroxymethylglutaryl-coa reductase inhibitors, double-blind method, atherosclerosis, ezetimibe, pcsk9 inhibitors
16 autores
- Michelle L. O’Donoghue🇨🇭🇺🇸University of Geneva; University of Bern; Brigham and Women's Hospital; Mount Sinai Hospital; Harvard University; University of California, Los Angeles; University Hospital of Geneva; Thrombolysis in Myocardial Infarction Study Group; Icahn School of Medicine at Mount Sinai
- Robert S. Rosenson🇨🇭🇺🇸University of Geneva; University of Bern; Brigham and Women's Hospital; Mount Sinai Hospital; Harvard University; University of California, Los Angeles; University Hospital of Geneva; Thrombolysis in Myocardial Infarction Study Group; Icahn School of Medicine at Mount Sinai
- Bariş Gencer🇨🇭🇺🇸University of Geneva; University of Bern; Brigham and Women's Hospital; Mount Sinai Hospital; Harvard University; University of California, Los Angeles; University Hospital of Geneva; Thrombolysis in Myocardial Infarction Study Group; Icahn School of Medicine at Mount Sinai
- J. Antonio G. López🇨🇭🇺🇸University of Geneva; University of Bern; Brigham and Women's Hospital; Amgen (United States); Mount Sinai Hospital; Harvard University; University of California, Los Angeles; University Hospital of Geneva; Thrombolysis in Myocardial Infarction Study Group; Icahn School of Medicine at Mount Sinai
- Norman E. Lepor🇨🇭🇺🇸University of Geneva; University of Bern; Brigham and Women's Hospital; Mount Sinai Hospital; Harvard University; University of California, Los Angeles; University Hospital of Geneva; Thrombolysis in Myocardial Infarction Study Group; Icahn School of Medicine at Mount Sinai
- Seth J. Baum🇨🇭🇺🇸University of Geneva; University of Bern; Brigham and Women's Hospital; Mount Sinai Hospital; Harvard University; University of California, Los Angeles; University Hospital of Geneva; Thrombolysis in Myocardial Infarction Study Group; Florida Atlantic University; Icahn School of Medicine at Mount Sinai
- Elmer Stout🇨🇭🇺🇸University of Geneva; University of Bern; Brigham and Women's Hospital; Mount Sinai Hospital; Harvard University; University of California, Los Angeles; University Hospital of Geneva; Thrombolysis in Myocardial Infarction Study Group; Icahn School of Medicine at Mount Sinai
- Daniel Gaudet🇨🇭🇺🇸🇨🇦University of Geneva; University of Bern; Brigham and Women's Hospital; Mount Sinai Hospital; Harvard University; University of California, Los Angeles; University Hospital of Geneva; Thrombolysis in Myocardial Infarction Study Group; Université de Montréal; Icahn School of Medicine at Mount Sinai
- Beat Knüsel🇨🇭🇺🇸University of Geneva; University of Bern; Brigham and Women's Hospital; Amgen (United States); Mount Sinai Hospital; Harvard University; University of California, Los Angeles; University Hospital of Geneva; Thrombolysis in Myocardial Infarction Study Group; Icahn School of Medicine at Mount Sinai
- Julia Kuder🇨🇭🇺🇸University of Geneva; University of Bern; Brigham and Women's Hospital; Mount Sinai Hospital; Harvard University; University of California, Los Angeles; University Hospital of Geneva; Thrombolysis in Myocardial Infarction Study Group; Icahn School of Medicine at Mount Sinai
- Xinhui Ran🇨🇭🇺🇸University of Geneva; University of Bern; Brigham and Women's Hospital; Mount Sinai Hospital; Harvard University; University of California, Los Angeles; University Hospital of Geneva; Thrombolysis in Myocardial Infarction Study Group; Icahn School of Medicine at Mount Sinai
- Sabina A. Murphy🇨🇭🇺🇸University of Geneva; University of Bern; Brigham and Women's Hospital; Mount Sinai Hospital; Harvard University; University of California, Los Angeles; University Hospital of Geneva; Thrombolysis in Myocardial Infarction Study Group; Icahn School of Medicine at Mount Sinai
- Huei Wang🇨🇭🇺🇸University of Geneva; University of Bern; Brigham and Women's Hospital; Amgen (United States); Mount Sinai Hospital; Harvard University; University of California, Los Angeles; University Hospital of Geneva; Thrombolysis in Myocardial Infarction Study Group; Icahn School of Medicine at Mount Sinai
- You Wu🇨🇭🇺🇸University of Geneva; University of Bern; Brigham and Women's Hospital; Amgen (United States); Mount Sinai Hospital; Harvard University; University of California, Los Angeles; University Hospital of Geneva; Thrombolysis in Myocardial Infarction Study Group; Icahn School of Medicine at Mount Sinai
- Helina Kassahun🇨🇭🇺🇸University of Geneva; University of Bern; Brigham and Women's Hospital; Amgen (United States); Mount Sinai Hospital; Harvard University; University of California, Los Angeles; University Hospital of Geneva; Thrombolysis in Myocardial Infarction Study Group; Icahn School of Medicine at Mount Sinai
- Marc Steven Sabatine🇨🇭🇺🇸University of Geneva; University of Bern; Brigham and Women's Hospital; Mount Sinai Hospital; Harvard University; University of California, Los Angeles; University Hospital of Geneva; Thrombolysis in Myocardial Infarction Study Group; Icahn School of Medicine at Mount Sinai
Resumen
El texto original del estudio, en el idioma en que se publicó.
Background
Lipoprotein(a) is a presumed risk factor for atherosclerotic cardiovascular disease. Olpasiran is a small interfering RNA that reduces lipoprotein(a) synthesis in the liver.
Methods
We conducted a randomized, double-blind, placebo-controlled, dose-finding trial involving patients with established atherosclerotic cardiovascular disease and a lipoprotein(a) concentration of more than 150 nmol per liter. Patients were randomly assigned to receive one of four doses of olpasiran (10 mg every 12 weeks, 75 mg every 12 weeks, 225 mg every 12 weeks, or 225 mg every 24 weeks) or matching placebo, administered subcutaneously. The primary end point was the percent change in the lipoprotein(a) concentration from baseline to week 36 (reported as the placebo-adjusted mean percent change). Safety was also assessed.
Results
Among the 281 enrolled patients, the median concentration of lipoprotein(a) at baseline was 260.3 nmol per liter, and the median concentration of low-density lipoprotein cholesterol was 67.5 mg per deciliter. At baseline, 88% of the patients were taking statin therapy, 52% were taking ezetimibe, and 23% were taking a proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitor. At 36 weeks, the lipoprotein(a) concentration had increased by a mean of 3.6% in the placebo group, whereas olpasiran therapy had significantly and substantially reduced the lipoprotein(a) concentration in a dose-dependent manner, resulting in placebo-adjusted mean percent changes of -70.5% with the 10-mg dose, -97.4% with the 75-mg dose, -101.1% with the 225-mg dose administered every 12 weeks, and -100.5% with the 225-mg dose administered every 24 weeks (P<0.001 for all comparisons with baseline). The overall incidence of adverse events was similar across the trial groups. The most common olpasiran-related adverse events were injection-site reactions, primarily pain.
Conclusions
Olpasiran therapy significantly reduced lipoprotein(a) concentrations in patients with established atherosclerotic cardiovascular disease. Longer and larger trials will be necessary to determine the effect of olpasiran therapy on cardiovascular disease. (Funded by Amgen; OCEAN[a]-DOSE ClinicalTrials.gov number, NCT04270760.).
Resumen vía Europe PMC. Los derechos de autor siguen siendo de los autores o la editorial.
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