Edoxaban vs. Warfarin in High-risk Patients with Atrial Fibrillation: A Comprehensive Analysis of High-Risk Subgroups.

Gencer, Baris; Eisen, Alon; Berger, David; Nordio, Francesco; Murphy, Sabina A; Grip, Laura T; Chen, Cathy; Lanz, Hans; Ruff, Christian T; Antman, Elliott M; Braunwald, Eugene; Giugliano, Robert P (2022). Edoxaban vs. Warfarin in High-risk Patients with Atrial Fibrillation: A Comprehensive Analysis of High-Risk Subgroups. American Heart Journal, 247, pp. 24-32. Elsevier 10.1016/j.ahj.2021.12.017

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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 the highest in patients with malignancy (19.2%), increased fall risk (14.0%), and very-low body weight (13.5%). The NCO rates increased with numbers of high-risk factors in the warfarin arm: 4.5%, 7.2%, 9.9% and 14.6% in patients with 0-1, 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=0.065 and P<0.001, respectively).

CONCLUSION

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.

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