Oral Muvalaplin for Lowering of Lipoprotein(a): A Randomized Clinical Trial
Nicholls SJ, Ni W, Rhodes GM, Nissen SE, Navar AM, Michael LF, Haupt A, Krege JH
JAMA · 124 citas
Etiquetas de revisión
Financiación no declaradaDatos neutrales que nuestra revisión registró sobre cómo se hizo este estudio. Describen el método, nunca si nos gusta el resultado.
Cómo se estudió
- Diseño
- Ensayo controlado aleatorizado (indexado por PubMed)
- Estudiado en
- Personas
- Resultado principal
- Marcadores de salud y funcionamiento
Quién lo pagó
- Financiación
- Financiación no declarada
Publicación
- Publicado
- 2024-11-18 · JAMA · vol. 333 · número 3 · pág. 222
- Editorial
- American Medical Association
- Citado
- 156 citas · más que el 100% de estudios similares · 59.6× el promedio de su campo
- Impacto
- Entre el 10 % más citado de su campo
- Referencias
- 29 trabajos
- Acceso
- Acceso abierto (copia en repositorio)
- Áreas de investigación
- Lipoproteins and Cardiovascular Health · Lipid metabolism and disorders · Cholesterol and Lipid Metabolism
- Palabras clave
- lipoprotein(a), apolipoprotein(a), apolipoprotein B, high-sensitivity C-reactive protein, atherosclerotic cardiovascular disease, familial hypercholesterolemia, diabetes mellitus, cardiovascular risk, lipid-lowering therapy, drug safety and tolerability, dose comparison
- MeSH
- humans, cardiovascular diseases, diabetes mellitus, lipoprotein(a), c-reactive protein, apolipoproteins b, administration, oral, double-blind method, aged, middle aged, female, male, atherosclerosis, hyperlipoproteinemia type ii, hypolipidemic agents
8 autores
- Stephen James Nicholls🇦🇺Monash University
- Wei Ni🇺🇸Eli Lilly (United States)
- Grace M. Rhodes🇺🇸Eli Lilly (United States)
- Steven E. Nissen🇺🇸Cleveland Clinic
- Ann Marie Návar🇺🇸The University of Texas Southwestern Medical Center
- Laura F. Michael🇺🇸Eli Lilly (United States)
- Axel Haupt🇺🇸Eli Lilly (United States)
- John Henry Krege🇺🇸Eli Lilly (United States)
Resumen
El texto original del estudio, en el idioma en que se publicó.
Importance
Muvalaplin inhibits lipoprotein(a) formation. A 14-day phase 1 study demonstrated that muvalaplin was well tolerated and reduced lipoprotein(a) levels up to 65%. The effect of longer administration of muvalaplin on lipoprotein(a) levels in individuals at high cardiovascular risk remains uncertain.
Objectives
To determine the effect of muvalaplin on lipoprotein(a) levels and to assess safety and tolerability.
Design, setting, and participants
Phase 2, placebo-controlled, randomized, double-blind trial enrolling 233 participants with lipoprotein(a) concentrations of 175 nmol/L or greater with atherosclerotic cardiovascular disease, diabetes, or familial hypercholesterolemia at 43 sites in Asia, Europe, Australia, Brazil, and the United States between December 10, 2022, and November 22, 2023.
Interventions
Participants were randomized to receive orally administered muvalaplin at dosages of 10 mg/d (n = 34), 60 mg/d (n = 64), or 240 mg/d (n = 68) or placebo (n = 67) for 12 weeks.
Main outcomes and measures
The primary end point was the placebo-adjusted percentage change from baseline in lipoprotein(a) molar concentration at week 12, using an assay to measure intact lipoprotein(a) and a traditional apolipoprotein(a)-based assay. Secondary end points included the percentage change in apolipoprotein B and high-sensitivity C-reactive protein.
Results
The median age of study participants was 66 years; 33% were female; and 27% identified as Asian, 4% as Black, and 66% as White. Muvalaplin resulted in placebo-adjusted reductions in lipoprotein(a) of 47.6% (95% CI, 35.1%-57.7%), 81.7% (95% CI, 78.1%-84.6%), and 85.8% (95% CI, 83.1%-88.0%) for the 10-mg/d, 60-mg/d, and 240-mg/d dosages, respectively, using an intact lipoprotein(a) assay and 40.4% (95% CI, 28.3%-50.5%), 70.0% (95% CI, 65.0%-74.2%), and 68.9% (95% CI, 63.8%-73.3%) using an apolipoprotein(a)-based assay. Dose-dependent reductions in apolipoprotein B were observed at 8.9% (95% CI, -2.2% to 18.8%), 13.1% (95% CI, 4.4%-20.9%), and 16.1% (95% CI, 7.8%-23.7%) at 10 mg/d, 60 mg/d, and 240 mg/d, respectively. No change in high-sensitivity C-reactive protein was observed. No safety or tolerability concerns were observed at any dosage.
Conclusions and relevance
Muvalaplin reduced lipoprotein(a) measured using intact lipoprotein(a) and apolipoprotein(a)-based assays and was well tolerated. The effect of muvalaplin on cardiovascular events requires further investigation.
Trial registration
ClinicalTrials.gov Identifier: NCT05563246.
Resumen vía Europe PMC. Los derechos de autor siguen siendo de los autores o la editorial.
Confianza de la comunidad
Cargando…
¿Cuánto confías en los hallazgos de este estudio?
Comentarios
¿Algo está mal aquí?
Señala este estudio si su información, etiquetas o financiación parecen incorrectas. Un editor revisa cada señalamiento.
Información educativa sobre investigación publicada. No es consejo médico ni una recomendación para empezar o dejar nada.