Real-world outcomes of edoxaban-treated AF patients

Two-year follow-up analysis of the Global ETNA-AF program showed low annualized clinical event rates for any stroke and major bleeding in AF patients treated with edoxaban at baseline in daily clinical practice, consistent with the 1-year follow-up findings.

This summary is based on the publication of De Caterina R, Unverdorben M, Chen C, et al. - Two-Year Follow-Up of Patients With Atrial Fibrillation Receiving Edoxaban in Routine Clinical Practice: Results From the Global ETNA-AF Program. Clin Cardiol. 2025 Feb;48(3):e70091. doi: 10.1002/clc.70091.

Introduction and methods

Background

RCT and real-world data have shown that DOACs reduce the risk of thromboembolic events in patients with AF compared with VKAs and have similar or lower bleeding risk [1-5]. Still, long-term data demonstrating their effectiveness and safety in daily clinical practice and in diverse patient populations are needed. Analysis of the Global ETNA-AF (Edoxaban Treatment in routiNe clinical practice in patients with nonvalvular Atrial Fibrillation) program indicated AF patients treated with edoxaban in routine care in Asia and Europe showed low incidences of stroke, intracranial hemorrhage, and other major bleeding events (all <2%) at 1 year [6].

Aim of the study

In a 2-year analysis of the Global ETNA-AF program, the authors investigated the effectiveness and safety of edoxaban in AF patients in daily clinical practice, globally and by region.

Methods

The Global ETNA-AF program integrates data of AF patients treated with edoxaban at baseline from several prospective, observational, noninterventional studies in Europe (Germany, Austria, Switzerland, Belgium, Italy, Spain, the UK, Ireland, the Netherlands, and Portugal), Japan, and non-Japanese Asian regions (Hong Kong, South Korea, Taiwan, and Thailand) [7]. The current analysis comprised 26,805 patients: 13,164 (49.1%) from Europe, 10,342 (38.6%) from Japan, and 3299 (12.3%) from non-Japanese Asian regions. Annualized clinical event rates were assessed in the first year and conditionally in patients who were event-free ≤12 months in the second year.

Outcomes

Effectiveness endpoints were all-cause mortality, CV death, MI, any stroke (ischemic stroke and hemorrhagic stroke), ischemic stroke, TIA, hemorrhagic stroke, and systemic embolic events. Safety endpoints included major bleeding, intracranial hemorrhage, major gastrointestinal (GI) bleeding, clinically relevant nonmajor bleeding, and minor bleeding, according to the International Society on Thrombosis and Haemostasis definitions.

Main results

Incidences over 2 years

• At baseline, European patients displayed the highest burden of comorbidities, including hypertension, COPD, MI, and peripheral artery disease, compared with patients in Japan and non-Japanese Asian regions (all P<0.0001).
• Over the 2-year follow-up period, the global annualized clinical event rate was 3.11% (95%CI: 2.95%–3.27%) for all-cause mortality, 0.79% (95%CI: 0.71%–0.87%) for CV death, 0.88% (95%CI: 0.80%–0.97%) for any stroke, 0.70% (95%CI: 0.63%–0.78%) for ischemic stroke, and 0.15% (95%CI: 0.12%–0.19%) for hemorrhagic stroke.
• At the 2-year follow-up, the global annualized event rate was 1.11% (95%CI: 1.02%–1.21%) for major bleeding, 0.27% (95%CI: 0.23%–0.32%) for intracranial hemorrhage and 0.41% (95%CI: 0.36%–0.48%) for major GI bleeding.
• When analyzed by region, the annualized event rate for 2-year all-cause mortality was numerically highest in Europe (3.94%; 95%CI: 3.70%–4.20%) and lowest in non-Japanese Asian regions (1.81%; 95%CI: 1.50%–2.18%).
• In contrast, the annualized event rate over 2 years for any stroke was highest in Japan (1.17%; 95%CI: 1.01%–1.35%) and lowest in Europe (0.63%; 95%CI: 0.54%–0.74%), as was that for major bleeding (1.38%; 95%CI: 1.21%–1.58% vs. 0.94%; 95%CI: 0.83%–1.07%).

Incidences in first and second year

• Globally, the annualized event rates in the first year and second year were 3.05% (95%CI: 2.84%–3.27%) and 3.18% (95%CI: 2.95%–3.43%), respectively, for all-cause mortality; 0.84% (95%CI: 0.73%–0.96%) and 0.73% (95%CI: 0.63%–0.86%), respectively, for CV death; 1.06% (95%CI: 0.94%–1.19%) and 0.65% (95%CI: 0.55%–0.77%), respectively, for any stroke; and 0.83% (95%CI: 0.73%–0.95%) and 0.54% (95%CI: 0.45%–0.65%), respectively, for ischemic stroke.
• The global annualized event rates in the first and second year were 1.31% (95%CI: 1.18%–1.45%) and 0.86% (95%CI: 0.74%–1.00%), respectively, for major bleeding; 0.32% (95%CI: 0.26%–0.40%) and 0.21% (95%CI: 0.16%–0.28%), respectively, for intracranial hemorrhage; and 0.47% (95%CI: 0.39%–0.56%) and 0.34% (95%CI: 0.27%–0.43%), respectively, for major GI bleeding.

Conclusion

This 2-year follow-up analysis of the Global ETNA-AF program showed low annualized clinical event rates for any stroke (0.9%) and major bleeding (1.1%) in AF patients treated with edoxaban at baseline in daily clinical practice. These rates were slightly lower in the second year than in the first year. Differences in annualized event rates for all-cause mortality, any stroke, and major bleeding were observed between Europe, Japan, and non-Japanese Asian regions, which “may reflect variations in baseline characteristics,” according to the authors.

Find this article online at Clin Cardiol.

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