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Lower limb revascularization in CLTI entails a high risk of major adverse limb events (MALE) and major adverse cardiovascular events (MACE). This scientific statement addresses this risk based on a systematic review. A structured literature search was performed, and articles were independently evaluated by two investigators. In total, 1678 articles were identified, of which 34 were included in the final analysis. Only three randomized controlled trials (RCTs) addressed antithrombotic therapy in CLTI following LLR. None of these demonstrated superiority of any antithrombotic regimen over the other. Eight RCTs investigated antithrombotic therapy following LLR in populations with peripheral arterial disease including CLTI subgroups and suggest a benefit of dual antiplatelet therapy on limb events. One large RCT demonstrated that dual pathway inhibition with aspirin and vascular-dose rivaroxaban reduced the risk of MALE, MACE, and unplanned target limb revascularization. Data from 22 observational studies suggest a benefit of dual antiplatelet therapy on overall survival and amputation-free survival after LLR as compared with single antiplatelet therapy. Intensified antithrombotic treatment should be proposed in patients with CLTI following LLR to reduce the risk of MALE and MACE. Randomized controlled trials on antithrombotic therapy in patients with CLTI following LLR are scarce. Dual pathway inhibition is the only regimen for which an RCT demonstrated a reduction of MALE and MACE following LLR. Dual antiplatelet therapy appears to be associated with a reduced risk of MALE in CLTI following LLR.<\/jats:p>","DOI":"10.1093\/eurheartj\/ehaf317","type":"journal-article","created":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T10:48:35Z","timestamp":1747738115000},"page":"2742-2759","source":"Crossref","is-referenced-by-count":8,"title":["Antithrombotic treatment following revascularization for chronic limb-threatening ischaemia: a scientific statement of the European Society of Cardiology Working Group on Aorta and Peripheral Vascular Diseases and the European Society of Cardiology Working Group on Cardiovascular Pharmacotherapy"],"prefix":"10.1093","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6934-5355","authenticated-orcid":false,"given":"Oliver","family":"Schlager","sequence":"first","affiliation":[{"name":"Division of Angiology, Department of Internal Medicine II, Medical University of Vienna , Vienna 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Vascular Medicine, Toulouse University Hospital , Toulouse ,","place":["France"]},{"name":"Unit\u00e9 Mixte de Recherche (UMR) 1301 Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM), RESTORE, Toulouse III\u2013Paul Sabatier University , Toulouse ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3212-8995","authenticated-orcid":false,"given":"Christian","family":"Heiss","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Surrey , Guildford ,","place":["UK"]},{"name":"Vascular Department, Surrey and Sussex Healthcare NHS Trust , Redhill ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7229-9780","authenticated-orcid":false,"given":"Jose","family":"Rodriguez Palomares","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Vall d\u2019Hebron Hospital Universitari, Vall d\u2019Hebron Barcelona Hospital Campus , Barcelona ,","place":["Spain"]},{"name":"Cardiovascular Diseases, Vall d\u2032Hebron Institut de Recerca (VHIR), Vall d\u2019Hebron Barcelona Hospital Campus , Barcelona ,","place":["Spain"]},{"name":"Department of Medicine, Universitat Aut\u00f2noma de Barcelona , Bellaterra ,","place":["Spain"]},{"name":"CIBER de Enfermedades Cardiovasculares, Instituto de Salud Carlos III , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3406-2878","authenticated-orcid":false,"given":"Joao C A","family":"Morais","sequence":"additional","affiliation":[{"name":"ciTechCare\u2014Center for Innovative Care and Health Technology, Polytechnic of Leiria , Leiria 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