Comparative Effects of Emerging Lp(a)-Lowering Agents and PCSK9-Directed Therapies on Lipoprotein(a): A Network Meta-Analysis of Randomised Clinical Trials
Zayed JA, Al-Awamleh NA, Hamad M, Hdaib MIM, Ayesh H
Diabetes, obesity & metabolism · 2 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
Según la declaración de financiación del texto completo.
Publicación
- Publicado
- 2026-06-04 · Diabetes Obes Metab · vol. 28 · número 8 · págs. 7403–7415
- Editorial
- Wiley
- Citado
- 1 cita · más que el 96% de estudios similares · 6.5× el promedio de su campo
- Impacto
- Entre el 10 % más citado de su campo
- Referencias
- 62 trabajos
- Acceso
- Acceso abierto (revista híbrida) · CC-BY
- Áreas de investigación
- Lipoproteins and Cardiovascular Health · Lipid metabolism and disorders · Cholesterol and Lipid Metabolism
- Palabras clave
- lipoprotein(a), Lp(a)-lowering therapy, PCSK9 inhibitors, siRNA, antisense oligonucleotides, olpasiran, pelacarsen, evolocumab, alirocumab, LDL cholesterol lowering, injection site reactions, serious adverse events, atherosclerotic cardiovascular disease
- MeSH
- humans, lipoprotein(a), anticholesteremic agents, cholesterol, ldl, randomized controlled trials as topic, proprotein convertase 9, pcsk9 inhibitors
5 autores
- Jihad Abu Zayed🇯🇴University of Jordan
- Nada A. Al‐Awamleh🇯🇴University of Jordan
- Mahmoud Hamad🇯🇴University of Jordan
- Mohammad Ibrahim Mahmoud Hdaib🇯🇴University of Jordan
- Hazem Ayesh🇺🇸 · autor de correspondenciaDeaconess Hospital
Resumen
El texto original del estudio, en el idioma en que se publicó.
Aims
Elevated lipoprotein(a) [Lp(a)] is a genetic ASCVD risk factor that often persists despite intensive LDL-C lowering. We compared the efficacy and safety of emerging Lp(a)-targeted therapies (siRNAs, antisense oligonucleotides and an oral assembly inhibitor) with PCSK9-directed therapies.
Materials and methods
We searched PubMed, Embase, Web of Science and Cochrane CENTRAL through December 6, 2025, for randomised trials in adults (≥ 18 years) with ≥ 8-week follow-up reporting Lp(a). The primary outcome was placebo-adjusted mean difference (MD) in percent change from baseline in Lp(a) (percentage points, pp). Secondary outcomes included LDL-C, other lipid parameters and safety outcomes (injection-site reactions, serious adverse events (SAEs), discontinuations). We performed a frequentist random-effects network meta-analysis in R (netmeta) and ranked interventions using P-scores.
Results
Fifty-one trials (17 810 participants) formed a 16-node network. Olpasiran 225 mg Q12W was associated with the greatest Lp(a) reduction versus placebo (MD -98.94 pp, 95% CI -114.36 to -83.52); pelacarsen, muvalaplin, zerlasiran and lepodisiran were also associated with large reductions. PCSK9-directed therapies were associated with more modest Lp(a) reductions (evolocumab 140 mg Q2W: MD -31.58 pp), but greater LDL-C lowering. The primary Lp(a) network showed high heterogeneity (I 2 = 90.9%) and funnel plot asymmetry, although treatment rankings remained directionally consistent across sensitivity analyses. No therapy was associated with higher SAEs or discontinuations versus placebo; alirocumab 150 mg was associated with more injection-site reactions.
Conclusions
Lp(a)-targeted therapies were associated with larger Lp(a) reductions than PCSK9-directed therapies, while PCSK9-directed therapies had greater LDL-C lowering. Given high heterogeneity, funnel plot asymmetry and low certainty for several estimates, these findings should be interpreted cautiously pending cardiovascular outcome trials.
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