{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T08:28:44Z","timestamp":1786609724357,"version":"build-2736575974"},"reference-count":72,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Curr Atheroscler Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose of Review<\/jats:title>\n                    <jats:p>Lipoprotein(a) [Lp(a)] is a genetically determined, independent risk factor for atherosclerotic cardiovascular disease and calcific aortic valve stenosis. Plasma Lp(a) levels are 70\u201390% heritable, largely unresponsive to lifestyle changes, and poorly controlled with typical lipid-lowering drugs such as statins and PCSK9 inhibitors. The development of powerful RNA-based therapies offers a new chance to specifically target and significantly lower Lp(a). We examined available phase 1\u20133 trial data, regulatory updates, and trial registries up to mid-2026 to provide an overview of the current pipeline, ongoing cardiovascular outcomes trials (CVOTs), and new mechanistic and genomic methods.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Recent Findings<\/jats:title>\n                    <jats:p>Five agents across three mechanisms have reached late-stage development. Pelacarsen, a GalNAc-conjugated antisense oligonucleotide (ASO), reduces Lp(a) by about 80% via hepatic apo(a) mRNA reduction and is the subject of the phase 3 Lp(a) HORIZON trial, with results due in late 2026. Three small interfering RNA (siRNA) drugs, olpasiran (&gt;\u200995% reduction, OCEAN(a)-Outcomes), lepodisiran (93.9% reduction lasting over 12 months after one dose, ACCLAIM-Lp(a)), and zerlasiran (96.4% reduction), allow quarterly or possibly yearly dosing. Muvalaplin, the first oral small-molecule Lp(a) inhibitor, interferes with apo(a)-ApoB particle formation and reduces intact Lp(a) by up to 85.8% in phase 2 KRAKEN trials; its phase 3 CVOT (MOVE-Lp(a)) is underway. Additionally, CRISPR\/Cas9-based liver gene editing targeting the LPA gene (CTX320) has entered phase 1 studies. All agents have shown good safety so far.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Summary<\/jats:title>\n                    <jats:p>The Lp(a) treatment landscape has moved from basic science to an active late-stage clinical pipeline. Positive outcomes from these CVOTs could lead to regulatory approvals and guideline updates affecting hundreds of millions of high-risk patients globally. Recent guidelines now recommend universal Lp(a) measurement, in anticipation of more effective therapies becoming available within the next 1 to 2 years.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s11883-026-01453-9","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T07:45:58Z","timestamp":1786607158000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Novel Lipoprotein (a) Therapies: A Comprehensive Review"],"prefix":"10.1007","volume":"28","author":[{"given":"Ugochukwu","family":"Ebubechukwu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Onyinye","family":"Ugoala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rameen","family":"Shahid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anandita","family":"Kulkarni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,13]]},"reference":[{"issue":"1","key":"1453_CR1","doi-asserted-by":"publisher","first-page":"e48","DOI":"10.1161\/ATV.0000000000000147","volume":"42","author":"G Reyes-Soffer","year":"2022","unstructured":"Reyes-Soffer G, et al. 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