Comparative efficacy and safety of novel Lp(a)-lowering therapies for ASCVD prevention: a network meta-analysis
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 oligonucleoti...
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| Autori principali: | , , , , , , , |
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| Natura: | Article (Journal) |
| Lingua: | inglese |
| Pubblicazione: |
May 2026
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| In: |
Pharmacological research
Year: 2026, Volume: 227, Pages: 1-10 |
| ISSN: | 1096-1186 |
| DOI: | 10.1016/j.phrs.2026.108178 |
| Accesso online: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.phrs.2026.108178 Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S1043661826000939 
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| Note sull'autore: | An-xin Wu, Xing-jin Wang, Chen Zhao, Jia-qiang Hu, Jin-wei Li, Ying Xu, Yi Li, Song Liu |
| Riassunto: | 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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| Descrizione del documento: | Gesehen am 21.08.2026 |
| Descrizione fisica: | Online Resource |
| ISSN: | 1096-1186 |
| DOI: | 10.1016/j.phrs.2026.108178 |