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Dr. Sander van Doorn and Dr. Christian Ruff discuss current and future treatment options for stroke prevention in patients with atrial fibrillation, focusing upon their FRAIL-AF and AZALEA studies. Dr. Sander van Doorn is General Practitioner and PhD at the Julius Center for Health Sciences and Primary Care of the University Medical Center Utrecht of Utrecht University (Netherlands), and author of the FRAIL-AF study that compared vitamin K antagonists (VKA) and direct oral anticoagulants (DOAC) for stroke prevention in frail patients with atrial fibrillation. Dr. Christian T. Ruff is Director of General Cardiology in the Cardiovascular Division at Brigham and Women’s Hospital in Boston, MA, and Associate Professor of Medicine at Harvard Medical School. Dr. Ruff is a Senior Investigator in the Thrombolysis in Myocardial Infarction (TIMI) Study Group, and within the TIMI group, he is principal investigator of the AZALEA study, a large phase 2 study that compared the novel factor XI antagonist abelacimab with rivaroxaban for stroke prevention in atrial fibrillation. The interview was recorded on April 5th, 2024. Moderators: Prof. Marlies Antlanger (Linz, Austria), Prof. Stephan Schirmer (Kaiserslautern, Germany) and Prof. Dr. Gunnar Heine (Frankfurt / Homburg, Germany). Articles discussed: Safety of Switching From a Vitamin K Antagonist to a Non-Vitamin K Antagonist Oral Anticoagulant in Frail Older Patients With Atrial Fibrillation: Results of the FRAIL-AF Randomized Controlled Trial. Joosten LPT, van Doorn S, van de Ven PM, Köhlen BTG, Nierman MC, Koek HL, Hemels MEW, Huisman MV, Kruip M, Faber LM, Wiersma NM, Buding WF, Fijnheer R, Adriaansen HJ, Roes KC, Hoes AW, Rutten FH, Geersing GJ. Circulation 2024 doi: 10.1161/CIRCULATIONAHA.123.066485 Liver-heart cross-talk mediated by coagulation factor XI protects against heart failure. Cao Y et al. Science 2022 doi: 10.1126/science.abn0910 Low-Dose Edoxaban in Very Elderly Patients with Atrial Fibrillation. Okumura K et al.; ELDERCARE-AF Committees and Investigators. N Engl J Med 2020 doi: 10.1056/NEJMoa2012883 Pharmacological targeting of coagulation factor XI mitigates the development of experimental atherosclerosis in low-density lipoprotein receptor-deficient mice. Ngo ATP et al. J Thromb Haemost 2021 doi: 10.1111/jth.15236 A Phase II randomized controlled trial evaluated antithrombotic treatment with fesomersen in patients with kidney failure on hemodialysis. Winkelmayer WC, Lensing AWA, Thadhani RI, Mahaffey KW, Walsh M, Pap ÁF, Willmann S, Thelen K, Hodge S, Solms A, Ingham SJM, Eikelboom J; RE-THINC investigators Kidney Int 2024 doi: 10.1016/j.kint.2024.02.024 Apixaban for Stroke Prevention in Subclinical Atrial Fibrillation. Healey JS et al.; ARTESIA Investigators. N Engl J Med 2023 doi: 10.1056/NEJMoa2310234 Anticoagulation with osocimab in patients with kidney failure undergoing hemodialysis: a randomized phase 2 trial. Weitz JI, Tankó LB, Floege J, Fox KAA, Bhatt DL, Thadhani R, Hung J, Pap ÁF, Kubitza D, Winkelmayer WC; CONVERT Investigators Nat Med 2024 doi: 10.1038/s41591-023-02794-7 KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. Kidney Int 2024 doi: 10.1016/j.kint.2023.10.018 Factor XI Inhibitors: Potential Role in End-Stage Kidney Disease. Ades M, Simard C, Vanassche T, Verhamme P, Eikelboom J, Mavrakanas TA Semin Nephrol 2024 doi: 10.1016/j.semnephrol.2023.151484 Anticoagulation with Edoxaban in Patients with Atrial High-Rate Episodes. Kirchhof P et al.; NOAH-AFNET 6 Investigators. N Engl J Med 2023 doi: 10.1056/NEJMoa2303062 Rivaroxaban in Rheumatic Heart Disease-Associated Atrial Fibrillation. Connolly SJ et al.; INVICTUS Investigators. N Engl J Med 2022 doi: 10.1056/NEJMoa2209051 Direct Oral Anticoagulants in Patients With Active Cancer: A Systematic Review and Meta-Analysis. Sabatino J, De Rosa S, Polimeni A, Sorrentino S, Indolfi C. JACC CardioOncol 2020 doi: 10.1016/j.jaccao.2020.06.001 Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Ruff CT, Giugliano RP, Braunwald E, Hoffman EB, Deenadayalu N, Ezekowitz MD, Camm AJ, Weitz JI, Lewis BS, Parkhomenko A, Yamashita T, Antman EM Lancet 2014 doi: 10.1016/S0140-6736(13)62343-0 Pharmacology and Clinical Development of Factor XI Inhibitors. Greco A, Laudani C, Spagnolo M, Agnello F, Faro DC, Finocchiaro S, Legnazzi M, Mauro MS, Mazzone PM, Occhipinti G, Rochira C, Scalia L, Capodanno D Circulation 2023 doi: 10.1161/CIRCULATIONAHA.122.062353