Thromb Haemost
DOI: 10.1055/s-0040-1716540
Coagulation and Fibrinolysis

Edoxaban versus Warfarin in Patients with Atrial Fibrillation at the Extremes of Body Weight: An Analysis from the ENGAGE AF-TIMI 48 Trial

Giuseppe Boriani
1  Cardiology Division, Department of Biomedical, Metabolic and Neural Sciences, University of Modena & Reggio Emilia, Modena University Hospital, Modena, Italy
,
Christian T. Ruff
2  TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital and Department of Medicine, Harvard Medical School, Boston, Massachusetts, United States
,
Julia F. Kuder
2  TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital and Department of Medicine, Harvard Medical School, Boston, Massachusetts, United States
,
Minggao Shi
3  Daiichi Sankyo Inc., Basking Ridge, New Jersey, United States
,
Hans J. Lanz
4  Daiichi Sankyo Europe GmbH, Munich, Germany
,
Elliott M. Antman
2  TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital and Department of Medicine, Harvard Medical School, Boston, Massachusetts, United States
,
Eugene Braunwald
2  TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital and Department of Medicine, Harvard Medical School, Boston, Massachusetts, United States
,
Robert P. Giugliano
2  TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital and Department of Medicine, Harvard Medical School, Boston, Massachusetts, United States
› Author Affiliations

Abstract

Background The effects of anticoagulants at extremes of body weight (BW) are not well described. The aim of this study was to analyze the pharmacokinetics/pharmacodynamics and clinical outcomes in patients randomized to warfarin, higher dose edoxaban (HDER), and lower dose edoxaban (LDER) regimens at extremes of BW in ENGAGE AF-TIMI 48.

Methods and Results We analyzed three BW groups: low BW (LBW: <5th percentile, ≤55 kg, N = 1,082), middle BW (MBW: 45th–55th percentile, 79.8–84 kg, N = 2,153), and high BW (HBW: >95th percentile, ≥120 kg, N = 1,093). In the warfarin arm, LBW patients had higher rates of stroke/systemic embolism (SSE: 6.5 vs. 4.7 in MBW vs. 1.6% in HBW, P trend < 0.001), major bleeding (MB: 9.3 vs. 7.7 vs. 6.5%, P trend = 0.08), and worse net clinical outcome of systemic embolic event, MB, or death (31.5 vs. 19.1 vs. 16.0%, P trend < 0.0001). The time-in-therapeutic range with warfarin was lowest in LBW patients (63.0 vs. 69.3 vs. 70.1% patients, P trend < 0.001). The pharmacokinetic/pharmacodynamic profile of edoxaban was consistent across BW groups. The risk of SSE was similar between HDER and warfarin for each of the three weight groups (P int = 0.52, P int-trend = 0.86). MB was reduced by LDER versus warfarin (P int = 0.061, P int-trend = 0.023), especially in LBW patients. Net clinical outcomes were improved by HDER versus warfarin (P int = 0.087, P int-trend = 0.027), especially in LBW patients.

Conclusion Patients with LBW in ENGAGE AF-TIMI 48 had in general a more fragile clinical status and poorer international normalized ratio control. The pharmacokinetic/pharmacodynamic profile of edoxaban was consistent across extremes of BW, resulting in similar efficacy compared with warfarin, while major or clinically relevant non-MB and net outcomes were most favorable with edoxaban as compared to warfarin in LBW patients.

Supplementary Material



Publication History

Received: 29 April 2020

Accepted: 03 August 2020

Publication Date:
13 September 2020 (online)

Georg Thieme Verlag KG
Stuttgart · New York