{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T21:46:43Z","timestamp":1792014403685,"version":"4.4.0"},"reference-count":55,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:00:00Z","timestamp":1791936000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:00:00Z","timestamp":1791936000000},"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 an independent, genetically determined, and causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and calcific aortic valve stenosis. Elevated Lp(a) affects approximately 20% of the global population and is not meaningfully modified by lifestyle intervention or existing lipid-lowering pharmacotherapy. This review summarizes the biology of Lp(a) as a therapeutic target, evaluates the efficacy of currently available lipid-lowering agents against this target, and describes the mechanistic principles, clinical evidence, and unresolved questions associated with RNA-based and emerging small-molecule and gene-editing approaches to Lp(a) reduction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Recent Findings<\/jats:title>\n                    <jats:p>Four RNA-directed agents targeting hepatic apolipoprotein(a) [apo(a)] synthesis have entered phase 2\/3 development. This includes pelacarsen, an antisense oligonucleotide (ASO), and olpasiran, zerlasiran, and lepodisiran, which are N-acetylgalactosamine (GalNAc)-conjugated small interfering RNAs (siRNAs). Phase 2 data demonstrate Lp(a) reductions ranging from 79% to approximately 97% on a placebo-adjusted basis, approaching the practical limit of apo(a) suppression, with favorable short-term safety profiles. A fifth, structurally distinct siRNA conjugated with GalNAc at both strand termini has recently completed first-in-human testing, sustaining reductions up to 97% through 48 weeks after a single dose without injection-site reactions. Recently, the topline results of phase 3 Lp(a) HORIZON (pelacarsen) were released and demonstrate a substantial Lp(a) reduction without meeting the trial\u2019s primary composite cardiovascular endpoint. Two further outcomes trials, OCEAN(a)-Outcomes (olpasiran) and ACCLAIM-Lp(a) (lepodisiran), remain ongoing. An oral small molecule, muvalaplin, achieved comparable reductions in phase 2 testing. Lastly, early non-human primate data, together with a completed phase 1 trial of an analogous CRISPR-Cas9 construct targeting a related hepatic lipid gene, support the feasibility of a CRISPR-Cas9-based gene-editing approach capable of durable apo(a) suppression from a single administration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Summary<\/jats:title>\n                    <jats:p>The pharmacology of Lp(a) suppression is now well characterized across three distinct therapeutic modalities. Whether the magnitude of biochemical reduction observed translates into a meaningful and safe reduction in cardiovascular events across different populations remains undetermined and will be addressed by the ongoing outcomes trials.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s11883-026-01474-4","type":"journal-article","created":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T08:22:54Z","timestamp":1791966174000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["RNA-Based Therapies for Lipoprotein(a) Reduction: Antisense Oligonucleotides, Small Interfering RNAs, and Emerging Platforms"],"prefix":"10.1007","volume":"28","author":[{"given":"Vibhu","family":"Parcha","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera A.","family":"Bittner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,14]]},"reference":[{"issue":"39","key":"1474_CR1","doi-asserted-by":"crossref","first-page":"3925","DOI":"10.1093\/eurheartj\/ehac361","volume":"43","author":"F Kronenberg","year":"2022","unstructured":"Kronenberg F, Mora S, Stroes ESG, et al. 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