{"id":"82081537b50f","type":"article","url":"https://hartvaat.nl/2019/07/16/edoxaban-versus-warfarine-bij-af-met-leverziekte-engage-af-timi-48/","title":"Edoxaban versus warfarine bij AF met leverziekte: ENGAGE AF-TIMI 48","title_en":"Edoxaban Versus Warfarin in Patients With Atrial Fibrillation and History of Liver Disease.","category":"atriumfibrilleren","category_label":"Atriumfibrilleren","professions":["apotheker","cardioloog"],"tags":[],"journal":"Journal of the American College of Cardiology","doi":"10.1016/j.jacc.2019.04.061","source_url":"https://doi.org/10.1016/j.jacc.2019.04.061","authors":["Arman Qamar","Elliott M Antman","Christian T Ruff","Francesco Nordio","Sabina A Murphy","Laura T Grip","Norton J Greenberger","Ophelia Q P Yin","Youngsook Choi","Hans J Lanz","Michele F Mercuri","Eugene Braunwald","Robert P Giugliano"],"significance":5,"published":"2019-07-16","source_date":"2019-07-16","image":"","kennis":["https://hartvaat.nl/kennis/antistolling/edoxaban/","https://hartvaat.nl/kennis/antistolling/doac-versus-vka-keuze/"],"congress":"","summary_en":"This ENGAGE AF-TIMI 48 subanalysis showed that edoxaban maintains its favorable profile compared with warfarin in AF patients with liver disease, a population traditionally excluded from anticoagulation trials.","created":"2026-07-03T10:28:02Z","updated":"2026-07-03T13:27:14Z","licence":"Citeer vrij, met bronvermelding en een link naar hartvaat.nl (de url van het record). Samenvattingen zijn redactioneel werk van HartVaat; de oorspronkelijke publicaties blijven van hun uitgevers (doi). Geen medisch advies.","body_markdown":"ENGAGE AF-TIMI 48 subanalyse bij AF-patiënten met een voorgeschiedenis van leverziekte.","abstract_original":"BACKGROUND: Patients with liver disease have increased risk of thrombosis and bleeding but are typically excluded from trials of direct oral anticoagulant agents. OBJECTIVES: This study evaluated the pharmacokinetics (PK), pharmacodynamics (PD), clinical efficacy and safety of edoxaban versus warfarin in patients with atrial fibrillation (AF) and history of liver disease. METHODS: ENGAGE AF-TIMI 48 (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis In Myocardial Infarction Study 48) was a randomized, double-blind trial comparing edoxaban with warfarin in patients with AF followed for 2.8 years. History of liver disease was defined as investigator-reported liver disease or >2-fold transaminase elevation at randomization. The primary efficacy and safety endpoints of stroke or systemic embolic event (SSEE) and major bleeding were assessed stratified by history of liver disease. PK/PD assessments of edoxaban included endogenous and extrinsic factor Xa activity and edoxaban concentration. RESULTS: Among 21,105 patients, 1,083 (5.1%) had a history of liver disease; they had a higher prevalence of many comorbidities. The adjusted risks of SSEE were similar (adjusted hazard ratio [HRadj]: 0.90; 95% confidence interval [CI]: 0.67 to 1.22; p = 0.50), but major bleeding was more common in patients with liver disease (HRadj: 1.38; 95% CI: 1.10 to 1.74; p = 0.005). There were no significant differences in PK/PD assessment of edoxaban in patients with versus without liver disease. The HRs for higher-dose edoxaban versus warfarin for SSEE were 0.86 (95% CI: 0.73 to 1.01) in patients without and 1.11 (95% CI: 0.54 to 2.30) with liver disease (p for interaction [pint] = 0.47), major bleeding 0.80 (95% CI: 0.70 to 0.91) in patients without and 0.91 (95% CI: 0.56 to 1.47) with liver disease (pint = 0.63). There were no significant differences in hepatic adverse events between the 2 treatment groups. CONCLUSIONS: Among patients with AF receiving oral anticoagulation, bleeding, but not thromboembolic events, was increased in patients with liver disease. A history of liver disease did not alter the relative efficacy and safety of edoxaban compared with warfarin. Hepatic adverse events were similar between edoxaban and warfarin."}