Association of diabetes mellitus status and clinical outcomes of edoxaban in patients with atrial fibrillation: a sub-analysis from the ETNA-AF Asian registry
T F Chao, E K Choi, H F Tse, S Kiatchoosakun, M Clasen, J Van Zyl, M Unverdorben, J GoagAbstract
Introduction
Diabetes mellitus (DM) and atrial fibrillation (AF) share thrombosis-related mechanisms, resulting in an increased risk of thromboembolic stroke and systemic embolic events (SEE). However, DM patients also present with vascular complications and comorbidities that may influence bleeding risk, particularly in the context of anticoagulation therapy.
Purpose
To describe the association between DM status with clinical outcomes during a 2-year follow-up in patients with AF on edoxaban at baseline (BL).
Methods
ETNA-AF-ASCA is a prospective, observational, non-interventional study of patients with AF from South Korea/Taiwan, Thailand, and Hong Kong receiving edoxaban at BL. Clinical outcomes were characterised using annualised event rates (AERs; %/year) and Kaplan-Meier (KM) curves and stratified by DM status (no DM; DM: DM on insulin and DM not on insulin). In this exploratory analysis, Cox proportional hazards regression with stepwise selected adjustment assessed differences in outcomes according to the DM status. Variables with P<0.20 in univariable analyses were included as candidate variables for adjustment.
Results
Among 3299 patients on edoxaban at BL, 987 (29.9%) had DM, of whom 65 (7.0%) were insulin-treated. Patients with DM had higher CHA2DS2-VASc scores, and more frequently presented with hypertension and coronary heart disease compared with without diabetes (Table 1). AERs for ischaemic stroke (IS)/transient ischaemic attack (TIA)/SEE were 1.1%/yr in without DM, 1.5%/yr with DM not on insulin, and 0.8%/yr with DM on insulin. Major bleeding AERs were 0.9%/yr, 1.8%, and 0.0%/yr; and all-cause death (ACD) were 1.5%/yr, 2.4%/yr, and 2.5%/yr (Figure 1). Adjusted multivariable analysis revealed DM was independently associated with an increased risk of major gastrointestinal (GI) bleeding (HR [95% CI]: 2.97 [1.32–6.69], P=0.009) and net clinical outcome (NCO) defined as IS/SEE, major bleeding or ACD (1.37 [1.01–1.87], P=0.046) compared with no DM. Additionally, a numerical higher risk of major bleeding (1.70 [0.99–2.92], P=0.054) and cardiovascular mortality (2.36 [1.00–5.55], P=0.050) was observed in patients with vs. without DM. No significant differences were observed for IS alone (1.29 [0.69–2.41], P=0.432) and IS/TIA/SEE (0.84 [0.46–1.54], P=0.570). Comparison of patients with DM not on insulin with those with no DM yielded similar results.
Conclusions
In this analysis of patients with AF treated with edoxaban, DM was independently associated with significantly higher risks of major GI bleeding and NCO compared to those without DM. Despite the well-established association between DM and increased thromboembolic stroke risk, our findings did not demonstrate a significant increase in IS alone or IS/TIA/SEE among DM patients receiving edoxaban compared with without DM.