[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-detail-126870-en":3,"doc-seo-126870-105":30,"detail-sidebar-cat-0-en-105":91},{"code":4,"msg":5,"data":6},0,"success",{"doc_id":7,"user_id":8,"nickname":9,"user_avatar":10,"doc_module":4,"category_id":11,"category_name":12,"doc_title":13,"doc_description":14,"doc_content":15,"file_id":16,"file_url":17,"file_type":18,"file_size":19,"view_count":4,"is_deleted":4,"is_public":20,"is_downloadable":20,"audit_status":20,"page_count":21,"language":22,"language_code":23,"site_id":24,"html_lang":23,"table_of_contents":25,"faqs":26,"seo_title":27,"seo_description":14,"update_tm":28,"read_time":29},126870,1099523885336,"Violet","https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c",8,"Research & Report","Pleiotropic Effects of Direct Oral Anticoagulants in Chronic Heart Failure and Atrial Fibrillation - Machine Learning Analysis","Oral anticoagulant therapy (OAT) for atrial fibrillation includes vitamin K antagonists, historically exemplified by warfarin, and direct-acting oral anticoagulants (DOACs) such as dabigatran etexilate, rivaroxaban, apixaban, and edoxaban. Lower major bleeding risk makes switching from warfarin to DOACs common in AF, yet optimal understanding remains limited for patients with coexisting AF and heart failure. This study evaluates the effects of warfarin-to-DOAC switching in HF patients with AF using machine learning on clinical data, focusing on cardiac remodeling, clinical status, endothelial function, and inflammatory biomarkers.","molecules   \nArticle  \nPleiotropic Effects of Direct Oral Anticoagulants in Chronic  \nHeart Failure and Atrial Fibrillation: Machine Learning Analysis  \nMarco Mele 1,2,†, Antonietta Mele 1,†, Paola Imbrici 1, Francesco Samarelli 1, Rosa Purgatorio 1, Giorgia Dinoi 1, Michele Correale 2, Orazio Nicolotti 1, Annamaria De Luca 1, Natale Daniele Brunetti 3, Antonella Liantonio 1,* and Nicola Amoroso 1,4  \nCitation: Mele, M.; Mele, A.;  \nImbrici, P.; Samarelli, F.;  \nPurgatorio, R.; Dinoi, G.; Correale, M.; Nicolotti, O.; De Luca, A.; Brunetti, N.D.; et al. Pleiotropic Effects of Direct Oral Anticoagulants in Chronic Heart Failure and Atrial Fibrillation:  \nMachine Learning Analysis. Molecules 2024, 29, 2651. [https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.3390/molecules29112651](10.3390/molecules29112651)  \nAcademic Editor: Dmitri B. Kireev  \nReceived: 4 April 2024  \nRevised: 21 May 2024  \nAccepted: 30 May 2024  \nPublished: 4 June 2024  \nCopyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 Department of Pharmacy—Drug Sciences, University of Bari, Via Orabona 4, 70125 Bari, Italy; [drmelemarco@yahoo.it](drmelemarco@yahoo.it) (M.M.); [antonietta.mele@uniba.it](antonietta.mele@uniba.it) (A.M.); [paola.imbrici@uniba.it](paola.imbrici@uniba.it) (P.I.); [francesco.samarelli@uniba.it](francesco.samarelli@uniba.it) (F.S.); [rosa.purgatorio@uniba.it](rosa.purgatorio@uniba.it) (R.P.); [giorgia.dinoi@uniba.it](giorgia.dinoi@uniba.it) (G.D.); [orazio.nicolotti@uniba.it](orazio.nicolotti@uniba.it) (O.N.); [annamaria.deluca@uniba.it](annamaria.deluca@uniba.it) (A.D.L.); [nicola.amoroso@uniba.it](nicola.amoroso@uniba.it) (N.A.)  \n2 Department of Cardiology,“Ospedali Riuniti” University Hospital, Viale Pinto 1, 71100 Foggia, Italy; [michele.correale@libero.it](michele.correale@libero.it)  \n3 Department of Medical and Surgical Sciences, University of Foggia, Viale Pinto 1, 71100 Foggia, Italy; [nd.brunetti@unifg.it](nd.brunetti@unifg.it)  \n4 National Institute of Nuclear Physics, Section of Bari, Via Orabona 4, 70125 Bari, Italy  \n* Correspondence: [antonella.liantonio@uniba.it](antonella.liantonio@uniba.it)[ ](antonella.liantonio@uniba.it)† These authors contributed equally to this work.  \nAbstract: Oral anticoagulant therapy (OAT) for managing atrial fibrillation (AF) encompasses vitamin K antagonists (VKAs, such as warfarin), which was the mainstay of anticoagulation therapy before 2010, and direct-acting oral anticoagulants (DOACs, namely dabigatran etexilate, rivaroxaban, apixaban, edoxaban), approved for the prevention of AF stroke over the last thirteen years. Due to the lower risk of major bleeding associated with DOACs, anticoagulant switching is a common practice in AF patients. Nevertheless, there are issues related to OAT switching that still need to be fully understood, especially for patients in whom AF and heart failure (HF) coexist. Herein, the effective impact of the therapeutic switching from warfarin to DOACs in HF patients with AF, in terms of cardiac remodeling, clinical status, endothelial function and inflammatory biomarkers, was assessed by a machine learning (ML) analysis of a clinical database, which ultimately shed light on the real positive and pleiotropic effects mediated by DOACs in addition to their anticoagulant activity.  \nKeywords: DOACs; heart failure; atrial fibrillation; machine learning  \n1. Introduction  \nAtrial fibrillation (AF) is a frequent arrhythmia in patients with heart failure (HF) . AF prevalence depends on the clinical status of these patients with an incidence that increases along with the severity of HF [1] . The association between AF and HF is easily explainable as these two cond","cbCaijiEmIPo9rEJ","https://ap.wps.com/l/cbCaijiEmIPo9rEJ","pdf",2676167,1,12,"English","en",105,"# Introduction\n## Atrial fibrillation and heart failure relationship\n## Anticoagulation strategies in AF\n## Warfarin versus DOAC mechanisms\n## Safety and efficacy considerations","[{\"question\":\"Why is switching from warfarin to DOACs common in atrial fibrillation patients?\",\"answer\":\"DOACs are associated with a lower risk of major bleeding, which supports frequent anticoagulant switching practice in AF care.\"},{\"question\":\"Which DOACs are addressed in the study and how do they differ from warfarin?\",\"answer\":\"The study considers dabigatran etexilate and factor Xa inhibitors such as apixaban, rivaroxaban, and edoxaban, which act through antithrombin-independent mechanisms, unlike warfarin’s vitamin K pathway inhibition.\"},{\"question\":\"What outcomes does the machine learning analysis evaluate after switching therapy?\",\"answer\":\"It assesses cardiac remodeling, clinical status, endothelial function, and inflammatory biomarkers to characterize pleiotropic effects beyond anticoagulant activity.\"}]","Pleiotropic Effects of Direct Oral Anticoagulants in Chronic Heart Failure and Atrial Fibrillation - Machine Learning Analysis | PDF",1785935318,30,{"code":4,"msg":31,"data":32},"ok",{"site_id":24,"language":23,"slug":33,"title":13,"keywords":34,"description":14,"schema_data":35,"social_meta":86,"head_meta":88,"extra_data":90,"updated_unix":28},"pleiotropic-effects-of-direct-oral-anticoagulants-in-chronic-heart-failure-and-atrial-fibrillation-machine-learning-analysis","",{"@graph":36,"@context":85},[37,54,68],{"@type":38,"itemListElement":39},"BreadcrumbList",[40,44,48,51],{"item":41,"name":42,"@type":43,"position":20},"https://docshare.wps.com","Home","ListItem",{"item":45,"name":46,"@type":43,"position":47},"https://docshare.wps.com/document/","Document",2,{"item":49,"name":12,"@type":43,"position":50},"https://docshare.wps.com/document/research-report/",3,{"item":52,"name":13,"@type":43,"position":53},"https://docshare.wps.com/document/pleiotropic-effects-of-direct-oral-anticoagulants-in-chronic-heart-failure-and-atrial-fibrillation-machine-learning-analysis/126870/",4,{"url":52,"name":13,"@type":55,"author":56,"headline":13,"publisher":58,"fileFormat":61,"inLanguage":23,"description":14,"dateModified":62,"datePublished":62,"encodingFormat":61,"isAccessibleForFree":63,"interactionStatistic":64},"DigitalDocument",{"name":9,"@type":57},"Person",{"url":41,"name":59,"@type":60},"DocShare","Organization","application/pdf","2026-08-05",true,{"@type":65,"interactionType":66,"userInteractionCount":4},"InteractionCounter",{"@type":67},"ViewAction",{"@type":69,"mainEntity":70},"FAQPage",[71,77,81],{"name":72,"@type":73,"acceptedAnswer":74},"Why is switching from warfarin to DOACs common in atrial fibrillation patients?","Question",{"text":75,"@type":76},"DOACs are associated with a lower risk of major bleeding, which supports frequent anticoagulant switching practice in AF care.","Answer",{"name":78,"@type":73,"acceptedAnswer":79},"Which DOACs are addressed in the study and how do they differ from warfarin?",{"text":80,"@type":76},"The study considers dabigatran etexilate and factor Xa inhibitors such as apixaban, rivaroxaban, and edoxaban, which act through antithrombin-independent mechanisms, unlike warfarin’s vitamin K pathway inhibition.",{"name":82,"@type":73,"acceptedAnswer":83},"What outcomes does the machine learning analysis evaluate after switching therapy?",{"text":84,"@type":76},"It assesses cardiac remodeling, clinical status, endothelial function, and inflammatory biomarkers to characterize pleiotropic effects beyond anticoagulant activity.","https://schema.org",{"og:url":52,"og:type":87,"og:title":13,"og:site_name":59,"og:description":14},"article",{"robots":89,"canonical":52},"index,follow",{"doc_id":7,"site_id":24},{"code":4,"msg":5,"data":92},[93,97,101,105,110,115,120,122,127,130,134],{"id":20,"doc_module":4,"doc_module_name":46,"category_name":94,"show_sort_weight":95,"slug":96},"Story & Novel",90,"story-novel",{"id":47,"doc_module":4,"doc_module_name":46,"category_name":98,"show_sort_weight":99,"slug":100},"Literature",80,"literature",{"id":53,"doc_module":4,"doc_module_name":46,"category_name":102,"show_sort_weight":103,"slug":104},"Exam",70,"exam",{"id":106,"doc_module":4,"doc_module_name":46,"category_name":107,"show_sort_weight":108,"slug":109},5,"Comic",60,"comic",{"id":111,"doc_module":4,"doc_module_name":46,"category_name":112,"show_sort_weight":113,"slug":114},6,"Technology",50,"technology",{"id":116,"doc_module":4,"doc_module_name":46,"category_name":117,"show_sort_weight":118,"slug":119},7,"Healthcare",40,"healthcare",{"id":11,"doc_module":4,"doc_module_name":46,"category_name":12,"show_sort_weight":29,"slug":121},"research-report",{"id":123,"doc_module":4,"doc_module_name":46,"category_name":124,"show_sort_weight":125,"slug":126},9,"Religion & Spirituality",20,"religion-spirituality",{"id":125,"doc_module":4,"doc_module_name":46,"category_name":128,"show_sort_weight":125,"slug":129},"World Cup","world-cup",{"id":131,"doc_module":4,"doc_module_name":46,"category_name":132,"show_sort_weight":131,"slug":133},10,"Lifestyle","lifestyle",{"id":135,"doc_module":4,"doc_module_name":46,"category_name":136,"show_sort_weight":106,"slug":137},19,"General","general"]