TY - JOUR
T1 - Edoxaban versus Warfarin in high-risk patients with atrial fibrillation
T2 - A comprehensive analysis of high-risk subgroups
AU - Gencer, Baris
AU - Eisen, Alon
AU - Berger, David
AU - Nordio, Francesco
AU - Murphy, Sabina A.
AU - Grip, Laura T.
AU - Chen, Cathy
AU - Lanz, Hans
AU - Ruff, Christian T.
AU - Antman, Elliott M.
AU - Braunwald, Eugene
AU - Giugliano, Robert P.
N1 - Publisher Copyright:
© 2021 The Author(s)
PY - 2022/5
Y1 - 2022/5
N2 - Background: To compare the efficacy and safety of edoxaban vs warfarin in high-risk subgroups. Methods: ENGAGE AF-TIMI 48 was a multicenter randomized, double-blind, controlled trial in 21,105 patients with atrial fibrillation (AF) within 12 months and CHADS2 score >2 randomized to higher-dose edoxaban regimen (HDER) 60 mg/reduced 30 mg, lower-dose edoxaban regimen (LDER) 30 mg/reduced 15 mg, or warfarin, and followed for 2.8 years (median). The primary outcome for this analysis was the net clinical outcome (NCO), a composite of stroke/systemic embolism events, major bleeding, or death. Multivariable risk-stratification analysis was used to categorize patients by the number of high-risk features. Results: The annualized NCO rates in the warfarin arm were highest in patients with malignancy (19.2%), increased fall risk (14.0%), and very-low body weight (13.5%). The NCO rates increased with the numbers of high-risk factors in the warfarin arm: 4.5%, 7.2%, 9.9% and 14.6% in patients with 0 to 1, 2, 3, and >4 risk factors, respectively (Ptrend <0.001). Versus warfarin, HDER was associated with significant reductions of NCO in most of the subgroups: elderly, patients with moderate renal dysfunction, prior stroke/TIA, of Asian race, very-low body weight, concomitant single antiplatelet therapy, and VKA-naïve. With more high-risk features (0->4+), the absolute risk reductions favoring edoxaban over warfarin increased: 0.3%->2.0% for HDER; 0.4%->3.4% for LDER vs warfarin (P = .065 and P < .001, respectively). Conclusions: While underuse of anticoagulation in high-risk patients with AF remains common, substitution of effective and safer alternatives to warfarin, such as edoxaban, represents an opportunity to improve clinical outcomes.
AB - Background: To compare the efficacy and safety of edoxaban vs warfarin in high-risk subgroups. Methods: ENGAGE AF-TIMI 48 was a multicenter randomized, double-blind, controlled trial in 21,105 patients with atrial fibrillation (AF) within 12 months and CHADS2 score >2 randomized to higher-dose edoxaban regimen (HDER) 60 mg/reduced 30 mg, lower-dose edoxaban regimen (LDER) 30 mg/reduced 15 mg, or warfarin, and followed for 2.8 years (median). The primary outcome for this analysis was the net clinical outcome (NCO), a composite of stroke/systemic embolism events, major bleeding, or death. Multivariable risk-stratification analysis was used to categorize patients by the number of high-risk features. Results: The annualized NCO rates in the warfarin arm were highest in patients with malignancy (19.2%), increased fall risk (14.0%), and very-low body weight (13.5%). The NCO rates increased with the numbers of high-risk factors in the warfarin arm: 4.5%, 7.2%, 9.9% and 14.6% in patients with 0 to 1, 2, 3, and >4 risk factors, respectively (Ptrend <0.001). Versus warfarin, HDER was associated with significant reductions of NCO in most of the subgroups: elderly, patients with moderate renal dysfunction, prior stroke/TIA, of Asian race, very-low body weight, concomitant single antiplatelet therapy, and VKA-naïve. With more high-risk features (0->4+), the absolute risk reductions favoring edoxaban over warfarin increased: 0.3%->2.0% for HDER; 0.4%->3.4% for LDER vs warfarin (P = .065 and P < .001, respectively). Conclusions: While underuse of anticoagulation in high-risk patients with AF remains common, substitution of effective and safer alternatives to warfarin, such as edoxaban, represents an opportunity to improve clinical outcomes.
UR - http://www.scopus.com/inward/record.url?scp=85124842361&partnerID=8YFLogxK
U2 - 10.1016/j.ahj.2021.12.017
DO - 10.1016/j.ahj.2021.12.017
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C2 - 34990581
AN - SCOPUS:85124842361
SN - 0002-8703
VL - 247
SP - 24
EP - 32
JO - American Heart Journal
JF - American Heart Journal
ER -