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High-dose eicosapentaenoic acid (EPA) has shown effectiveness in reducing ASCVD risk in statin-treated patients, and is increasingly used within combination lipid-regulating strategies for those at highest risk. This review synthesizes the rationale for pairing high-dose EPA with intensive LDL reduction, particularly after acute coronary syndrome, and provides a practical treatment implementation algorithm and the role of EPA in preventing ASCVD in hypertriglyceridaemia.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/concept-and-practice-in-the-use-of-high-dose-eicosapentaenoic-acid-for-cardiovascular-disease-prevention-in-hypertriglyceridaemia/440445/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/concept-and-practice-in-the-use-of-high-dose-eicosapentaenoic-acid-for-cardiovascular-disease-prevention-in-hypertriglyceridaemia/440445.png","ImageObject",300,407,{"name":92,"@type":93},"PakDamar76","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-02","2026-09-29",true,{"@type":102,"interactionType":103,"userInteractionCount":29},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Why is hypertriglyceridaemia considered an additional target in ASCVD prevention?","Question",{"text":112,"@type":113},"Elevated plasma triglycerides and triglyceride-rich lipoproteins contribute to residual ASCVD risk even when LDL-C goals are achieved. They are linked causally by genetic evidence and relate positively to cardiovascular risk in epidemiological studies.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What evidence supports the use of high-dose EPA in reducing ASCVD risk?",{"text":117,"@type":113},"Clinical trials show that high-dose eicosapentaenoic acid reduces ASCVD risk in patients on statin therapy, including those with and without hypertriglyceridaemia. It is therefore incorporated into combination lipid-regulating strategies.",{"name":119,"@type":110,"acceptedAnswer":120},"How does the review connect plasma TG to triglyceride-rich lipoproteins and atherogenesis?",{"text":121,"@type":113},"Plasma TG reflects the total concentration of TRL in circulation, which include chylomicrons, VLDL, and their remnants. TRL promote atherogenesis through mechanisms such as endothelial dysfunction, cholesterol deposition, foam cell formation, and inflammatory or pro-thrombotic pathway activation.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},440445,1792638165,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":29,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":44,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":144,"preview_page_count":4},962090893057,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","Review  \n► Additional supplemental material is published online only. To view, please visit the journal online ([https://doi](https://doi). org/10.1136/heartjnl-2025- 325765) .  \n1Cardiology Department, AP-HP, Hôpital Bichat, Paris, France 2Cardiology Department, Centre Hospitalier de Versailles, Le Chesnay, France  \n3University of Glasgow Institute of Cardiovascular and Medical Sciences, Glasgow, UK 4Lipids and Arteriosclerosis Research Unit, Rovira i Virgili University, Reus, Spain 5Klinik und Poliklinik für Kardiologie, Universität Leipzig, Leipzig, Germany 6Multimedica IRCCS and University of Milan, Milan, Italy 7Université Paris-Cité,  \nFACT (French Alliance for Cardiovascular Trials), INSERM1148/LVTS and AP-HP, Hôpital Bichat, Paris, France  \nCorrespondence to  \nProfessor Chris J Packard; [chris.j.packard@gmail.com](chris.j.packard@gmail.com)  \nGR and CJP are joint first authors.  \nReceived 18 January 2025 Accepted 3 April 2025  \n© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.  \nTo cite: Roger G, Packard CJ, Masana L, et al. Heart Epub ahead of print: [please include Day Month Year] . doi:10 . 1136/ heartjnl-2025-325765  \nConcept and practice in the use of high-dose eicosapentaenoic acid for cardiovascular disease prevention in hypertriglyceridaemia  \nGuillaume Roger  , 1,2 Chris J Packard,3 Luis Masana,4 Ulrich Laufs,5 Alberico L Catapano,6 Philippe Gabriel Steg7  \nABSTRACT  \nGenetic and epidemiological evidence indicates that triglyceride-rich lipoproteins are causal risk factors for atherosclerotic cardiovascular disease (ASCVD) . Elevated levels of plasma triglyceride are common in patients who are diabetic or obese and contribute substantially to residual, ongoing risk of an ASCVD event in individualson low-density lipoprotein (LDL)-lowering treatment. Hypertriglyceridaemia, therefore, presents a target for further intervention. Clinical trials have demonstrated that high-dose eicosapentaenoic acid (EPA) is effective in reducing ASCVD risk in patients on statin therapy, and it is now being incorporated into strategies using combination lipid-regulating treatment to manage aggressively those at highest risk. This review summarisesthe concepts underpinning the use of high-dose EPA alongside intensive LDL-lowering therapy, especially in the context of post-acute coronary syndrome. A practical implementation algorithm is presented setting out treatment options for combination therapy, and the place of high-dose EPA in ASCVD prevention in hypertriglyceridaemia.  \nINTRODUCTION  \nIschaemic heart disease remains the main cause of death worldwide.1 Within its multifactorial aetiology low-density lipoprotein (LDL) and other apolipoprotein (apo) B-containing lipoproteins play a central, causal role, promoting the development of the underlying process of atherosclerosis. The use of statins and other drugs—ezetimibe, proprotein convertase subtilisin/ kexin type 9 (PCSK9) inhibitors, bempedoic acid—to lower LDL is a central strategy in the prevention of atherosclerotic cardiovascular disease (ASCVD) in both primary and secondary settings.2 However, in many individuals, a substantial ASCVD risk remains after LDL-cholesterol (LDL-C) goal achievement, and elevated plasma triglyceride (TG) is recognised as an important component of this residual risk.3 Plasma TG, or more specifically TG-rich lipoproteins (TRL), is therefore an additional target for lipid-lowering therapy. Outcome studies of TG lowering using classical drugs such as fibrates and high-dose niacin when added to statins failed to demonstrate further ASCVD risk reduction, although retrospective analyses suggest that subgroups characterised by high TG and low high-density lipoprotein (HDL) may have positive results.4–7 An alternative approach, treatment with high-dose eicosapentaenoic acid (EPA), has been shown to reduce cardiovascular risk in patients  \nwith (and without) h","cbCaihf4FVvwNaI0","https://ap.wps.com/l/cbCaihf4FVvwNaI0","pdf",2602181,"English","# Abstract\n# Introduction\n## LDL lowering and residual risk\n## Role of plasma triglycerides and TRL\n## Genetic and epidemiological relationship to cardiovascular risk\n## Pathogenic mechanisms of TRL in atherogenesis\n## Measuring plasma TG for clinical risk assessment","[{\"question\":\"Why is hypertriglyceridaemia considered an additional target in ASCVD prevention?\",\"answer\":\"Elevated plasma triglycerides and triglyceride-rich lipoproteins contribute to residual ASCVD risk even when LDL-C goals are achieved. They are linked causally by genetic evidence and relate positively to cardiovascular risk in epidemiological studies.\"},{\"question\":\"What evidence supports the use of high-dose EPA in reducing ASCVD risk?\",\"answer\":\"Clinical trials show that high-dose eicosapentaenoic acid reduces ASCVD risk in patients on statin therapy, including those with and without hypertriglyceridaemia. It is therefore incorporated into combination lipid-regulating strategies.\"},{\"question\":\"How does the review connect plasma TG to triglyceride-rich lipoproteins and atherogenesis?\",\"answer\":\"Plasma TG reflects the total concentration of TRL in circulation, which include chylomicrons, VLDL, and their remnants. TRL promote atherogenesis through mechanisms such as endothelial dysfunction, cholesterol deposition, foam cell formation, and inflammatory or pro-thrombotic pathway activation.\"}]","Concept and practice in the use of high-dose eicosapentaenoic acid for cardiovascular disease prevention in hypertriglyceridaemia | PDF",1790692234,23]