Real-world use and clinical outcomes among patients with atrial fibrillation using low-dose edoxaban and apixaban in Italy

Low-dose direct oral anticoagulants (DOACs) are indicated to mitigate bleeding risk during thromboprophylaxis for certain patients with atrial fibrillation (AF). No randomised clinical trials have directly compared outcomes with low-dose edoxaban vs apixaban; thus, assessing clinical outcomes with these treatments in routine clinical practice is important for informing patient management in this setting.

With strong evidence for the overall clinical benefit of low-dose edoxaban (the most recently approved DOAC in Italy), we aimed to evaluate its composite real-world clinical benefit in Italian patients with AF compared with low-dose apixaban (a formulation of the most prescribed DOAC in Italy) using a retrospective cohort study.

Adult patients with AF who received their first DOAC prescription as low-dose edoxaban (30 mg once daily) or apixaban (2.5 mg twice daily) between January 2016 and December 2021 were identified from the Italian IQVIA® Longitudinal Patient Database (comprises patient consultation and treatment data from general practitioners). To avoid bias from patients who switched to a low dose from the standard dose after an adverse event, patients who received any DOAC within 12 months prior to the new prescription were excluded. Clinical outcomes (ischaemic stroke or systemic embolism and any major bleeding) were compared using propensity-score matching between the edoxaban and apixaban groups. The weighted risks associated with clinical outcomes were calculated and hazard ratios (HRs) with 95% confidence intervals (CIs) reported.

In total, 2661 patients were identified, with 46.1% (n = 1226) using edoxaban 30 mg and 53.9% (n = 1435) using apixaban 2.5 mg (Table). Most patients were female (edoxaban, 65.9%; apixaban, 63.4%) and aged ≥75 years (edoxaban, 90.3%; apixaban, 96.0%). Incidence rates per 100 person-years before matching for ischaemic stroke or systemic embolism were 4.85 for edoxaban and 6.22 for apixaban; incidence rates per 100 person-years before matching for any major bleeding were 1.10 for edoxaban and 1.42 for apixaban. After adjusting for patient characteristics, each cohort comprised 1144 patients. Adjusted risk of ischaemic stroke or systemic embolism was significantly lower for edoxaban vs apixaban (HR, 0.68; 95% CI, 0.47–0.98; P <0.05; Figure). There was no significant difference in the adjusted risk of major bleeding between edoxaban and apixaban (HR, 0.83; 95% CI, 0.36–1.92; P = 0.7).

In routine clinical practice in Italy, most patients with AF who received low-dose edoxaban or apixaban were female and aged ≥75 years. Among these patients, low-dose edoxaban was associated with lower rates of ischaemic stroke and systemic embolism with no increased risk for major bleeding compared with low-dose apixaban.

EHRA 2025 HEOR low-dose Table