Financiado en parte por Novartis Pharma, Novartis Pharma AG
Inclisiran and cardiovascular events: a patient-level analysis of phase III trials
Ray KK, Raal FJ, Kallend DG, Jaros MJ, Koenig W, Leiter LA, Landmesser U, Schwartz GG, Lawrence D, Friedman A, Garcia Conde L, Wright RS, ORION Phase III investigators
European heart journal · 180 citas
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Cómo se estudió
- Diseño
- Metaanálisis (clasificado por nuestro filtro de IA)
- Estudiado en
- Personas
- Resultado principal
- Eventos clínicos como enfermedad o muerte
Quién lo pagó
- Financiación
- Financiado por la industria
- Empresa
- Novartis Pharma
- Empresa
- Novartis Pharma AG
Según 2 financiadores declarados y la declaración de financiación del texto completo.
Publicación
- Publicado
- 2022-10-07 · Eur Heart J · vol. 44 · número 2 · págs. 129–138
- Editorial
- Oxford University Press
- Citado
- 225 citas · más que el 100% de estudios similares · 38.6× el promedio de su campo
- Impacto
- Entre el 10 % más citado de su campo
- Referencias
- 24 trabajos
- Acceso
- Acceso abierto (revista híbrida) · CC-BY-NC
- Áreas de investigación
- Lipoproteins and Cardiovascular Health · Atherosclerosis and Cardiovascular Diseases · Antiplatelet Therapy and Cardiovascular Diseases
- Palabras clave
- inclisiran, siRNA, LDL cholesterol lowering, major adverse cardiovascular events, heterozygous familial hypercholesterolemia, atherosclerotic cardiovascular disease, myocardial infarction, stroke, cardiovascular safety
- MeSH
- humans, cardiovascular diseases, myocardial infarction, rna, small interfering, anticholesteremic agents, hydroxymethylglutaryl-coa reductase inhibitors, cholesterol, ldl, randomized controlled trials as topic, clinical trials, phase iii as topic, stroke
13 autores
- Kausik Kumar Ray🇬🇧 · autor de correspondenciaImperial College London
- Frederick Johan Raal🇿🇦University of the Witwatersrand
- David G. Kallend🇺🇸🇨🇦LIB Therapeutics LLC (United States); DalCor Pharmaceuticals (Canada)
- Mark J Jaros
- Wolfgang Köenig🇩🇪Universität Ulm; German Centre for Cardiovascular Research; Deutsches Herzzentrum München; Technical University of Munich
- Lawrence A. Leiter🇨🇦St. Michael's Hospital; University of Toronto
- Ulf Landmesser🇩🇪German Centre for Cardiovascular Research; Berlin Institute of Health at Charité - Universitätsmedizin Berlin; Charité - Universitätsmedizin Berlin
- Gregory G. Schwartz🇺🇸University of Colorado Anschutz; University of Colorado Denver
- David Lawrence🇨🇭Novartis (Switzerland)
- Andrew Friedman
- Lorena Garcia Conde🇨🇭Novartis (Switzerland)
- R. Scott Wright🇺🇸Mayo Clinic
- ORION Phase III investigators
Resumen
El texto original del estudio, en el idioma en que se publicó.
Background
Inclisiran, an siRNA administered twice-yearly, significantly reduced LDL cholesterol (LDL-C) in Phase III trials. Whether lowering LDL-C with inclisiran translates into a lower risk of cardiovascular (CV) events is not yet established.
Methods and results
Patient-level, pooled analysis of ORION-9, -10 and -11, included patients with heterozygous familial hypercholesterolaemia, atherosclerotic CV disease (ASCVD), or ASCVD risk equivalent on maximally tolerated statin-therapy, randomized 1:1 to receive 284 mg inclisiran or placebo on Days 1, 90, and 6-monthly thereafter for 18 months. Prespecified exploratory endpoint of major cardiovascular events (MACEs) included non-adjudicated CV death, cardiac arrest, non-fatal myocardial infarction (MI), and fatal and non-fatal stroke, evaluated as part of safety assessments using a standard Medical Dictionary for Regulatory Activities basket. Although not prespecified, total fatal and non-fatal MI, and stroke were also evaluated. Mean LDL-C at baseline was 2.88 mmol/L. At Day 90, the placebo-corrected percentage reduction in LDL-C with inclisiran was 50.6%, corresponding to an absolute reduction of 1.37 mmol/L (both P < 0.0001). Among 3655 patients over 18 months, 303 (8.3%) experienced MACE, including 74 (2.0%) fatal and non-fatal MIs, and 28 (0.8%) fatal and non-fatal strokes. Inclisiran significantly reduced composite MACE [OR (95% CI): 0.74 (0.58-0.94)], but not fatal and non-fatal MIs [OR (95% CI): 0.80 (0.50-1.27)] or fatal and non-fatal stroke [OR (95% CI): 0.86 (0.41-1.81)].
Conclusion
This analysis offers early insights into the potential CV benefits of lowering LDL-C with inclisiran and suggests potential benefits for MACE reduction. These findings await confirmation in the larger CV outcomes trials of longer duration.
Resumen vía Europe PMC. Los derechos de autor siguen siendo de los autores o la editorial (CC BY-NC).
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