Comparative efficacy and safety of novel Lp(a)-lowering therapies for ASCVD prevention: A network meta-analysis
Wu AX, Wang XJ, Zhao C, Hu JQ, Li JW, Xu Y, Li Y, Liu S
Pharmacological research · 0 citas
Cómo se estudió
- Diseño
- Metaanálisis (indexado por PubMed)
- Estudiado en
- Personas
- Resultado principal
- Marcadores de salud y funcionamiento
Quién lo pagó
- Financiación
- Financiación independiente
- Universidad u hospital
- Southwest Medical University
- Subvenciones
- Southwest Medical University (2025JC087)
Según 1 financiador declarado.
Publicación
- Publicado
- 2026-04-03 · Pharmacol Res · vol. 227 · pág. 108178
- Editorial
- Elsevier BV
- Citado
- 1 cita · más que el 94% de estudios similares · 6.3× el promedio de su campo
- Impacto
- Entre el 10 % más citado de su campo
- Referencias
- 60 trabajos
- Acceso
- Acceso abierto (revista) · CC-BY-NC-ND
- Áreas de investigación
- Lipoproteins and Cardiovascular Health · Lipid metabolism and disorders · Cholesterol and Lipid Metabolism
- Palabras clave
- lipoprotein(a), Lp(a)-lowering therapy, atherosclerotic cardiovascular disease prevention, siRNA, antisense oligonucleotides, olpasiran, pelacarsen, apolipoprotein B, LDL cholesterol, PCSK9 inhibitors, treatment response, injection site reactions, drug safety
- MeSH
- humans, lipoprotein(a), oligonucleotides, antisense, rna, small interfering, atherosclerosis, randomized controlled trials as topic, hypolipidemic agents
8 autores
- An-xin Wu🇨🇳Third People's Hospital of Chengdu
- Xing-jin Wang🇩🇪Heidelberg University
- Chen Zhao🇨🇳Capital Medical University; Nanchong Central Hospital
- Jiaqiang Hu
- Jinwei Li🇨🇳Southwest Medical University; Affiliated Hospital of Southwest Medical University
- Ying Xu🇨🇳Chengdu Medical College
- Yi Li🇨🇳 · autor de correspondenciaChengdu Medical College
- Song Liu🇨🇳 · autor de correspondenciaSouthwest Medical University; Affiliated Hospital of Southwest Medical University
Resumen
El texto original del estudio, en el idioma en que se publicó.
Elevated lipoprotein(a) [Lp(a)] is a genetically determined and independent risk factor for atherosclerotic cardiovascular disease (ASCVD) that is largely resistant to conventional lipid-lowering therapies. Novel Lp(a)-targeted agents, including small interfering RNA (siRNA), antisense oligonucleotides (ASO), and the oral small-molecule inhibitor muvalaplin, have shown potent efficacy in early trials. We conducted a systematic review and network meta-analysis to comprehensively compare their efficacy and safety. A total of 25 randomized controlled trials (RCTs) involving 7715 participants were included, evaluating six siRNA agents, four ASO agents, and one small-molecule inhibitor. The primary outcome was percentage change from baseline in Lp(a). Secondary outcomes included absolute change in Lp(a), percentage changes in apolipoprotein B (apoB) and low-density lipoprotein cholesterol (LDL-C), and adverse events. SiRNA therapies achieved the greatest Lp(a) reductions (olpasiran: mean difference [MD] -92.1%, 95% CI -100.1 to -84.0%; zerlasiran: -80.6%, 95% CI -87.7 to -73.5%), followed by muvalaplin (-76.8%, 95% CI -90.3 to -63.2%) and ASO therapy (pelacarsen: -54.2%, 95% CI -72.2 to -36.2%; all P < 0.001). Most agents achieved absolute Lp(a) reductions exceeding 105 nmol/L, suggesting clinically meaningful benefit. Baseline Lp(a) levels significantly modified treatment response (P < 0.001), and concomitant proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor use further enhanced LDL-C reduction (P = 0.024). All therapies were well tolerated, with injection-site reactions most frequent for injectables, while muvalaplin was well tolerated. These findings indicate that targeted Lp(a)-lowering therapies substantially reduce circulating Lp(a), with siRNA showing the greatest potency and muvalaplin offering a convenient oral alternative for personalized ASCVD risk reduction.
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