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

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.

• Authors: Giuseppe Boriani, Christian T Ruff, Julia F Kuder, Minggao Shi, Hans J Lanz, Elliott M Antman, Eugene Braunwald, Robert P Giugliano
• Journal: Thrombosis and haemostasis (Thromb Haemost) Vol. 121 Issue 2 Pg. 140-149 (Feb 2021) ISSN: 2567-689X [Electronic] Germany
• PMID: 32920808 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial)
• Copyright: Thieme. All rights reserved.

Chemical References

• Anticoagulants
• Factor Xa Inhibitors
• Pyridines
• Thiazoles
• Warfarin
• edoxaban

Topics

• Aged
• Aged, 80 and over
• Anticoagulants (pharmacokinetics, therapeutic use)
• Atrial Fibrillation (drug therapy)
• Body Weight
• Double-Blind Method
• Factor Xa Inhibitors (pharmacokinetics, therapeutic use)
• Female
• Humans
• Male
• Middle Aged
• Pyridines (pharmacokinetics, therapeutic use)
• Thiazoles (pharmacokinetics, therapeutic use)
• Treatment Outcome
• Warfarin (pharmacokinetics, therapeutic use)