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Evidence highlights antisense oligonucleotides, small-interfering RNAs, and oral inhibitors achieving large (often 80–90%) Lp(a) reductions. Ongoing outcome trials evaluate cardiovascular and valvular effects while emphasizing personalized prevention through routine Lp(a) measurement.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/emerging-therapies-targeting-lipoproteina-the-next-frontier-in-cardiovascular-risk-reduction/411121/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/emerging-therapies-targeting-lipoproteina-the-next-frontier-in-cardiovascular-risk-reduction/411121.png","ImageObject",300,407,{"name":42,"@type":43},"Rizky","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-11-01","2026-09-28",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",12,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What is lipoprotein(a) and how is it structurally organized?","Question",{"text":63,"@type":64},"Lp(a) is an LDL-like particle containing apolipoprotein B-100 linked to apolipoprotein(a) [apo(a)] via a disulfide bond. The apo(a) component includes multiple kringle domains with copy-number variation that influences Lp(a) size and circulating levels.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"Why does elevated Lp(a) increase cardiovascular risk?",{"text":68,"@type":64},"Elevated Lp(a) contributes through prothrombotic effects that interfere with fibrinolysis, proatherogenic LDL-like cholesterol deposition, and transport of oxidized phospholipids that drive vascular inflammation, monocyte recruitment, and plaque instability.",{"name":70,"@type":61,"acceptedAnswer":71},"What emerging therapies are being evaluated to lower Lp(a)?",{"text":72,"@type":64},"The review discusses antisense oligonucleotides (e.g., pelacarsen), small-interfering RNAs (e.g., olpasiran, lepodisiran, zerlasiran), and oral small-molecule inhibitors (e.g., muvalaplin). These approaches can markedly reduce circulating Lp(a), and large-scale outcome trials are underway to assess cardiovascular and valvular benefits.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},411121,1790621025,{"code":4,"msg":82,"data":83},"success",{"doc_id":79,"user_id":84,"nickname":42,"user_avatar":85,"doc_module":4,"category_id":86,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":87,"file_id":88,"file_url":89,"file_type":90,"file_size":91,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":92,"language":93,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":94,"faqs":95,"seo_title":96,"seo_description":12,"update_tm":97,"read_time":98,"preview_page_count":4},962085564807,"https://ap-avatar.wpscdn.com/davatar_6f874abed73319feea01a86fa6f0fab8",7,"OPEN ACCESS  \nEDITED BY  \nXingli Xu,  \nQilu Hospital of Shandong University, China  \nREVIEWED BY  \nQian Guo,  \nFirst Affiliated Hospital of Zhengzhou University, China  \nZonghao Pan,  \nConemaugh Memorial Medical Center, United States  \n*CORRESPONDENCE  \nIbrahim S. Alhomoud  \n [i.alhomoud@qu.edu.sa](i.alhomoud@qu.edu.sa)  \nRECEIVED 18 October 2025  \nREVISED 03 December 2025  \nACCEPTED 03 December 2025  \nPUBLISHED 18 December 2025  \nCITATION  \nAlhomoud IS (2025) Emerging therapies targeting lipoprotein(a): the next frontier in cardiovascular risk reduction.  \nFront. Med. 12:1727918 .  \ndoi: 10.3389/fmed.2025.1727918  \nCOPYRIGHT  \n© 2025 Alhomoud. This is an open-access article distributed under the terms of the  \nCreative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.  \nTYPE Review  \nPUBLISHED 18 December 2025 DOI 10.3389/fmed.2025.1727918  \nEmerging therapies targeting lipoprotein(a): the next frontier in cardiovascular risk reduction  \nIbrahim S. Alhomoud*  \nDepartment of Pharmacy Practice, College of Pharmacy, Qassim University, Qassim, Saudi Arabia  \nLipoprotein(a) [Lp(a)] is a genetically determined lipoprotein particle composed of apolipoprotein B-100 covalently linked to apolipoprotein(a) [apo(a)] via a disulfide bond. The Lp(a) particle is enriched with oxidized phospholipids (OxPLs), which confer enhanced atherogenic and pro-inflammatory properties compared with low-density lipoprotein (LDL) . Robust genetic and epidemiologic evidence demonstrates that elevated Lp(a) levels are independently associated with atherosclerotic cardiovascular disease and calcific aortic valve stenosis. However, no pharmacologic therapy has yet been approved that specifically lower Lp(a) or to demonstrate a reduction in cardiovascular events. Antisense oligonucleotides (e. g., pelacarsen), small-interfering RNAs (e. g., olpasiran, lepodisiran, and zerlasiran), and oral small-molecule Lp(a) inhibitors (e. g., muvalaplin) have demonstrated profound reductions in circulating Lp(a) concentrations, typically achieving decreases of 80–90% . In some studies, the reductions approached or achieved a near-complete suppression. Current genetic and modeling evidence suggests that an absolute reduction of at least 50 mg/dLin Lp(a) levels is required to achieve meaningful cardiovascular benefits. Largescale outcome trials are now underway to assess the effects of these emerging therapies on cardiovascular and valvular outcomes. Early findings indicate favorable effects on oxidized phospholipids and vascular inflammation, suggesting broader anti-atherogenic potential. As these agents progress toward clinical use, routine Lp(a) measurement and risk stratification will become increasingly essential for personalized cardiovascular prevention. This review summarizes the molecular biology of Lp(a), highlights the limitations of current therapies, and discusses emerging RNA-based and small-molecule approaches with the potential to redefine the management of residual cardiovascular risk.  \nKEYWORDS  \nantisense oligonucleotide, atherosclerotic cardiovascular disease, cardiovascular risk, lipoprotein(a), small interfering RNA  \n1 Structure and biochemistry of Lp(a)  \nLp(a) is an LDL-like particle composed of apolipoprotein B-100 (apoB-100) covalently linked to apo(a) via a disulfide bond ( 1, 2) . Apo(a) shares structural homology with plasminogen but lacks several functional domains (3) . The apo(a) component contains 10 distinct kringle IV subtypes (KIV-1 through KIV-10), a kringle V domain, and an inactive protease-like domain ( 1–3). The KIV-2 domain exhibits marked copy-number variation that substantially influences both the molecular size","cbCaigO1izAAEYOr","https://ap.wps.com/l/cbCaigO1izAAEYOr","pdf",671745,9,"English","# 1 Structure and biochemistry of Lp(a)\n## Lp(a) composition and apo(a) domains\n## KIV-2 copy-number variation and Lp(a) levels\n# 2 Pathogenic mechanisms of Lp(a) in cardiovascular disease\n## Prothrombotic, proatherogenic, and OxPL-mediated pathways\n# 3 Lipoprotein(a) as an independent risk factor for cardiovascular and valvular disease","[{\"question\":\"What is lipoprotein(a) and how is it structurally organized?\",\"answer\":\"Lp(a) is an LDL-like particle containing apolipoprotein B-100 linked to apolipoprotein(a) [apo(a)] via a disulfide bond. The apo(a) component includes multiple kringle domains with copy-number variation that influences Lp(a) size and circulating levels.\"},{\"question\":\"Why does elevated Lp(a) increase cardiovascular risk?\",\"answer\":\"Elevated Lp(a) contributes through prothrombotic effects that interfere with fibrinolysis, proatherogenic LDL-like cholesterol deposition, and transport of oxidized phospholipids that drive vascular inflammation, monocyte recruitment, and plaque instability.\"},{\"question\":\"What emerging therapies are being evaluated to lower Lp(a)?\",\"answer\":\"The review discusses antisense oligonucleotides (e.g., pelacarsen), small-interfering RNAs (e.g., olpasiran, lepodisiran, zerlasiran), and oral small-molecule inhibitors (e.g., muvalaplin). These approaches can markedly reduce circulating Lp(a), and large-scale outcome trials are underway to assess cardiovascular and valvular benefits.\"}]","Emerging therapies targeting lipoprotein(a): the next frontier in cardiovascular risk reduction | PDF",1790587518,23,{"code":4,"msg":82,"data":100},[101,105,109,113,118,123,126,131,135,138,142],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":102,"show_sort_weight":103,"slug":104},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":106,"show_sort_weight":107,"slug":108},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":110,"show_sort_weight":111,"slug":112},"Exam",70,"exam",{"id":114,"doc_module":4,"doc_module_name":25,"category_name":115,"show_sort_weight":116,"slug":117},5,"Comic",60,"comic",{"id":119,"doc_module":4,"doc_module_name":25,"category_name":120,"show_sort_weight":121,"slug":122},6,"Technology",50,"technology",{"id":86,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":124,"slug":125},40,"healthcare",{"id":127,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":129,"slug":130},8,"Research & Report",30,"research-report",{"id":92,"doc_module":4,"doc_module_name":25,"category_name":132,"show_sort_weight":133,"slug":134},"Religion & Spirituality",20,"religion-spirituality",{"id":133,"doc_module":4,"doc_module_name":25,"category_name":136,"show_sort_weight":133,"slug":137},"World Cup","world-cup",{"id":139,"doc_module":4,"doc_module_name":25,"category_name":140,"show_sort_weight":139,"slug":141},10,"Lifestyle","lifestyle",{"id":143,"doc_module":4,"doc_module_name":25,"category_name":144,"show_sort_weight":114,"slug":145},19,"General","general"]