Incidence and Predictors of Worsening Renal Function in Edoxaban-Treated Atrial Fibrillation Patients Within ETNA-AF-Europe Registry.

Background: Managing patients with atrial fibrillation (AF) and worsening renal function (WRF) remains a clinical challenge due to the need of dose adjustment of non-vitamin K antagonist oral anticoagulants.
Objectives: To determine the incidence of WRF in patients with AF treated with edoxaban, the association of WRF with clinical outcomes, and predictors of WRF and clinical outcomes in these patients.
Methods: This is a subanalysis of the Edoxaban Treatment in routiNe clinical prActice for patients with non-valvular Atrial Fibrillation in Europe study (NCT02944019), an observational study of edoxaban-treated patients with AF. WRF was defined as a ≥25% reduction in creatinine clearance between baseline and 2 years.
Results: Of the 9,054 patients included (69% of the total 13,133 enrolled), most did not experience WRF (90.3%) during the first 2 years of follow-up. WRF occurred in 9.7% of patients. Patients with WRF had significantly higher rates of all-cause death (3.88%/y vs 1.88%/y; P  < 0.0001), cardiovascular death (2.09%/y vs 0.92%/y; P  < 0.0001), and major bleeding (1.51%/y vs 0.98%/y; P  = 0.0463) compared with those without WRF. Rates of intracranial hemorrhage (0.18%/y vs 0.18%/y) and of any stroke/systemic embolic events were low (0.90%/y vs 0.69%/y; P  = 0.3161) in both subgroups. The strongest predictors of WRF were a high CHA ₂ DS ₂ -VASc score, high baseline creatinine clearance, low body weight, and older age. Most predictors of WRF were also predictors of clinical outcomes.
Conclusions: WRF occurred in approximately 10% of edoxaban-treated AF patients. Rates of death and major bleeding were significantly higher in patients with WRF than without. Stroke events were low in both subgroups.
Competing Interests: This study was funded by 10.13039/501100022274Daiichi Sankyo Europe GmbH, Munich, Germany. Dr Gwechenberger has received personal fees (lectures, advisory boards, research grants) and travel grants from Daiichi Sankyo, Boehringer Ingelheim, Bayer, Abbott, Biotronik, Boston, Medtronic, and Sorin. Dr Barón-Esquivias has received honoraria for presentations and/or consultancy fees and/or research grants from Boehringer Ingelheim, Bayer, Daiichi Sankyo, Pfizer-Bristol-Myers-Squibb, and Biotronik. Dr de Vries has received nonfinancial support from Daiichi Sankyo for other research projects related to the ETNA-AF-Europe registry, and speaker fees from Bristol Myers Squibb. He is also being considered for the adjudication committee of the LIMIT & DANCE trials, which are sponsored by the Population Health Research Institute (PHRI). Dr Siller-Matula has received speaker or consultant fees from Chiesi, Biosensors, Boston Scientific, P&F, Boehringer Ingelheim, and Daiichi Sankyo not related to the submitted work. Dr de Groot reports personal fees from Daiichi Sankyo during the conduct of the study; grants from Abbott, Atricure, Bayer, Boston Scientific, Daiichi Sankyo, Johnson & Johnson, and Medtronic; personal fees from Atricure, Bayer, berlin-Chemie, Daiichi Sankyo, Johnson & Johnson, Medtronic, Menarini, Novartis, and Servier; and other from RhythmCARE outside the submitted work. Dr Manu was an employee of Daiichi Sankyo Europe GmbH, Munich, Germany (at the time of development of the manuscript). Dr Souza is an employee of Daiichi Sankyo Europe GmbH, Munich, Germany. Dr Wienerroither is an employee of Daiichi Sankyo Austria GmbH, Vienna, Austria. Dr Pecen has received fees and honoraria from Daiichi-Sankyo, SOTIO, and Beckman Coulter. Dr De Caterina reports grants, personal fees and nonfinancial support from Daiichi Sankyo, during the conduct of the study; and reports consulting fees, honoraria and research funding from: AstraZeneca, Boehringer Ingelheim, Bayer, BMS/Pfizer, Daiichi Sankyo, Janssen, Milestone, Novartis, Merck, Portola, Sanofi, Menarini, Guidotti, and Roche, outside the submitted work. Dr Kirchhof receives research support for basic, translational, and clinical research projects from European Union Big-Data@Heart (grant agreement EU IMI 116 074); CATCH ME (grant agreement ID: 633 196); AFFECT-EU (grant agreement ID: 847 770); Leducq foundation, Medical Research Council (UK); German Centre for Cardiovascular Research supported by the German Ministry of Education and Research; from several drug and device companies active in atrial fibrillation and has received honoraria from several such companies in the past but not in the last 3 years. He is listed as inventor on 2 patents held by University of Birmingham (Atrial Fibrillation Therapy WO 2 015 140 571, Markers for Atrial Fibrillation WO 2 016 012 783) and is employed as Director of the Department of Cardiology, University Heart and Vascular Centre UKE Hamburg and Professor of Cardiovascular Medicine (part-time), University of Birmingham, UK. He is also Speaker of the board of AFNET, Germany, and Board member of the ESC.
(© 2024 The Authors.)