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It contrasts SWEDEHEART registry outcomes for On-X versus other bileaflet prostheses, reviews guideline changes shaped by PROACT, and highlights LOWERING-IT trial results in low-risk non-On-X patients. The letter argues that current recommendations rely on limited trials and historical cohorts, and describes the LIMIT randomized study as a large event-driven platform to test a unified lower INR strategy while maintaining thromboembolic protection.",{"@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/lower-international-normalized-ratio-anticoagulation-in-patients-with-mechanical-valves-needs-robust-evaluation-letter-to-the-editor/456618/",{"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/lower-international-normalized-ratio-anticoagulation-in-patients-with-mechanical-valves-needs-robust-evaluation-letter-to-the-editor/456618.png","ImageObject",300,407,{"name":92,"@type":93},"acoobca","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-09","2026-09-30",true,{"@type":102,"interactionType":103,"userInteractionCount":44},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What outcomes does the SWEDEHEART analysis compare for different mechanical aortic valves?","Question",{"text":112,"@type":113},"It compares long-term bleeding and thromboembolic outcomes influenced by INR targets, including cumulative major bleeding and thromboembolic event rates for On-X versus other mechanical valves.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How did the PROACT trial influence INR recommendations for On-X valves?",{"text":117,"@type":113},"PROACT supported reduced-intensity warfarin (INR 1.5–2.0) plus aspirin as noninferior for major clinical outcomes with fewer bleeding events, leading to guideline options for a lower INR strategy in specified On-X patients.",{"name":119,"@type":110,"acceptedAnswer":120},"What is the purpose and design of the LIMIT trial?",{"text":121,"@type":113},"LIMIT is a multicentre randomized prospective open-label blinded-end-point trial enrolling 2,625 patients with bileaflet aortic valves to test whether lower INR targets reduce major bleeding while preserving protection against thromboembolism.","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},456618,1791240091,{"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":44,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":8,"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":81,"preview_page_count":4},3985747870733,"https://ap-avatar.wpscdn.com/davatar_a8503ba1806abce46bf441b54a3ca4cd","Interdisciplinary CardioVascular and Thoracic Surgery 2025, 40(12), ivaf283 LETTER TO THE EDITOR  \n[https://doi.org/10.1093/icvts/ivaf283](https://doi.org/10.1093/icvts/ivaf283) Advance Access publication 1 December 2025  \nLower International Normalized Ratio Anticoagulation in Patients with Mechanical Valves Needs Robust Evaluation  \nReceived: October 6, 2025; Accepted: November 15, 2025  \nTo the Editor,  \nWe read with great interest the SWEDEHEART analysis1 by Lu et al evaluating long-term outcomes after mechanical aortic valve replacement. This large, nationwide registry-based study provides real-world data on bleeding and thromboembolic complications in contemporary practice, both of which are influenced by international normalized ratio (INR) targets. At 8 years, patients with an On-X prosthesis experienced cumulative incidences of 7.2% for major bleeding and 7.3% for thromboembolic events versus 7.0% and 6.4% for patients with other mechanical valves. Importantly, these outcomes did not differ meaningfully between On-X and other bileaflet prostheses, challenging the assumption that On-X valves’ design confers distinctive protection against thrombosis. These event rates underscore the persistent risks associated with lifelong anticoagulation in patients with mechanical valves.  \nGuideline recommendations have evolved in response to the PROACT trial.2 This trial showed that reduced-intensity warfarin (INR 1.5-2.0) plus aspirin was noninferior to standard therapy in patients with On-X aortic valves, with fewer bleeding events. On this basis, the 2017 ACC/AHA focused update introduced a Class IIb option for a lower INR in On-X aortic valves without additional risk factors, and in 2020, the full guideline formalized this recommendation with clearer parameters, including initiation 3 months post-surgery with concomitant aspirin. However, Lu et al’s findings suggest that similar outcomes may be expected across different models of bileaflet prostheses. They added that use of the lower INR target for On-X valves may have been inconsistent in routine care, and INR data were not available to assess adherence.  \nThe LOWERING-IT trial further suggested that the benefits of reduced-intensity anticoagulation are not confined to On-X valves.3 In 396 low-risk patients with non-On-X bileaflet aortic valves, targeting INR 1.5-2.5 was noninferior to 2.0-3.0 for thromboembolism and significantly reduced bleeding over more than 2,000 patient-years of follow-up. Despite these findings, current recommendations remain based on small trials and historical cohorts. In an international survey, we found that most clinicians recognized these limitations and were willing to randomize their patients to lower INR strategies.4  \nWhat is now required is a large, rigorously designed randomized trial, and the LIMIT trial (NCT03636295) has been developed to provide this evidence.5 LIMIT is a multicentre, randomized, prospective open-label blinded-end-point trial that will enroll 2,625 patients with bileaflet aortic valves worldwide. Eligible participants must be at least 3 months post-surgery and are randomized 1:1 to a low INR target (1.5-2.5) or to current guideline-recommended ranges. With sequential primary outcomes of noninferiority for thromboembolism and superiority for major bleeding, LIMIT is positioned to determine whether reduced-intensity anticoagulation can be safely extended  \nbeyond On-X valves. As of September 24, 2025, 869 patients have been enrolled in LIMIT. With an event-driven approach, LIMIT will definitively establish whether a unified, lower INR strategy for all bileaflet prostheses can reduce lifelong bleeding complications while preserving protection against thromboembolic events.  \nFUNDING  \nNone declared.  \nCONFLICTS OF INTEREST  \nDrs. Belley-Cote and Whitlock are the principal investigators of the LIMIT trial. They have received grant funding from Abbott. Dr. Belley-Cote has received consulting fees from Trimedic Therapeuticsand ","cbCaifsZik74ElJE","https://ap.wps.com/l/cbCaifsZik74ElJE","pdf",175159,"English","# Letter to the Editor\n## Rationale and prior evidence (SWEDEHEART, PROACT, LOWERING-IT)\n## Need for robust randomized evidence (LIMIT trial design and enrollment)\n## Funding and conflicts of interest\n## References","[{\"question\":\"What outcomes does the SWEDEHEART analysis compare for different mechanical aortic valves?\",\"answer\":\"It compares long-term bleeding and thromboembolic outcomes influenced by INR targets, including cumulative major bleeding and thromboembolic event rates for On-X versus other mechanical valves.\"},{\"question\":\"How did the PROACT trial influence INR recommendations for On-X valves?\",\"answer\":\"PROACT supported reduced-intensity warfarin (INR 1.5–2.0) plus aspirin as noninferior for major clinical outcomes with fewer bleeding events, leading to guideline options for a lower INR strategy in specified On-X patients.\"},{\"question\":\"What is the purpose and design of the LIMIT trial?\",\"answer\":\"LIMIT is a multicentre randomized prospective open-label blinded-end-point trial enrolling 2,625 patients with bileaflet aortic valves to test whether lower INR targets reduce major bleeding while preserving protection against thromboembolism.\"}]","Lower International Normalized Ratio Anticoagulation in Patients with Mechanical Valves Needs Robust Evaluation - Letter to the Editor | PDF",1790746527]