{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T16:32:27Z","timestamp":1791563547936,"version":"4.3.4"},"reference-count":80,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T00:00:00Z","timestamp":1780531200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T00:00:00Z","timestamp":1780531200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Elevated lipoprotein(a) [Lp(a)] is a genetic ASCVD risk factor that often persists despite intensive LDL\u2010C lowering. We compared the efficacy and safety of emerging Lp(a)\u2010targeted therapies (siRNAs, antisense oligonucleotides and an oral assembly inhibitor) with PCSK9\u2010directed therapies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>We searched PubMed, Embase, Web of Science and Cochrane CENTRAL through December 6, 2025, for randomised trials in adults (\u2265\u200918\u2009years) with \u2265\u20098\u2010week follow\u2010up reporting Lp(a). The primary outcome was placebo\u2010adjusted mean difference (MD) in percent change from baseline in Lp(a) (percentage points, pp). Secondary outcomes included LDL\u2010C, other lipid parameters and safety outcomes (injection\u2010site reactions, serious adverse events (SAEs), discontinuations). We performed a frequentist random\u2010effects network meta\u2010analysis in R (netmeta) and ranked interventions using P\u2010scores.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Fifty\u2010one trials (17\u2009810 participants) formed a 16\u2010node network. Olpasiran 225\u2009mg Q12W was associated with the greatest Lp(a) reduction versus placebo (MD \u221298.94 pp, 95% CI \u2212114.36 to \u221283.52); pelacarsen, muvalaplin, zerlasiran and lepodisiran were also associated with large reductions. PCSK9\u2010directed therapies were associated with more modest Lp(a) reductions (evolocumab 140\u2009mg Q2W: MD \u221231.58 pp), but greater LDL\u2010C lowering. The primary Lp(a) network showed high heterogeneity (\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u200990.9%) 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\u2009mg was associated with more injection\u2010site reactions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Lp(a)\u2010targeted therapies were associated with larger Lp(a) reductions than PCSK9\u2010directed therapies, while PCSK9\u2010directed therapies had greater LDL\u2010C lowering. Given high heterogeneity, funnel plot asymmetry and low certainty for several estimates, these findings should be interpreted cautiously pending cardiovascular outcome trials.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.70944","type":"journal-article","created":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T05:57:42Z","timestamp":1780639062000},"page":"7403-7415","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Comparative Effects of Emerging Lp(a)\u2010Lowering Agents and\n                    <scp>PCSK9<\/scp>\n                    \u2010Directed Therapies on Lipoprotein(a): A Network Meta\u2010Analysis of Randomised Clinical Trials"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-4284-5266","authenticated-orcid":false,"given":"Jihad Abu","family":"Zayed","sequence":"first","affiliation":[{"name":"School of Medicine University of Jordan  Amman Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4480-6175","authenticated-orcid":false,"given":"Nada A.","family":"Al\u2010Awamleh","sequence":"additional","affiliation":[{"name":"School of Medicine University of Jordan  Amman Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2782-2879","authenticated-orcid":false,"given":"Mahmoud","family":"Hamad","sequence":"additional","affiliation":[{"name":"School of Medicine University of Jordan  Amman Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4897-7901","authenticated-orcid":false,"given":"Mohammad Ibrahim Mahmoud","family":"Hdaib","sequence":"additional","affiliation":[{"name":"School of Medicine University of Jordan  Amman Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8231-705X","authenticated-orcid":false,"given":"Hazem","family":"Ayesh","sequence":"additional","affiliation":[{"name":"Deaconess Health System  Evansville Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,4]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.18553\/jmcp.2023.29.5.519"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahjo.2025.100581"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph18050753"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.18773\/austprescr.2016.060"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamacardio.2022.0987"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2022.09.021"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2025.1727918"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12170\u2010025\u201000760\u20101"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1912387"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.118.037184"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacadv.2024.101549"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2024.05.058"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2024.21957"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2023.21835"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2415818"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1905239"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2023.16503"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2024.24017"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11739\u2010016\u20101583\u20107"},{"key":"e_1_2_9_21_1","unstructured":"J.Abu ZayedandH.Ayesh Comparative Effects of Emerging Lp(a) Lowering Agents and PCSK9 Inhibitors on Lipoprotein(a): A Network Meta\u2010Analysis of Randomized Clinical Trials [Internet] 2025 https:\/\/osf.io\/bdmkt."},{"key":"e_1_2_9_22_1","first-page":"660","volume-title":"Statistical Inference","author":"Casella G.","year":"2002"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1177\/0962280216669183"},{"key":"e_1_2_9_24_1","volume-title":"RoB 2: A Revised Tool for Assessing Risk of Bias in Randomised Trials","author":"Sterne J. 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