Intracranial Haemorrhage and Haemorrhagic Stroke in Patients with Atrial Fibrillation on Edoxaban in ETNA-AF-Europe

Background/Objectives: ETNA-AF-Europe was a post-authorization, prospective, non-interventional study evaluating edoxaban in atrial fibrillation (AF). Here, we assessed annualized rates of intracranial haemorrhage, haemorrhagic stroke, and ischaemic stroke in subpopulations of edoxaban-treated patients with AF. Methods: We assessed overall annualized adjudicated event rates over 4 years, including subpopulations stratified by age, renal/hepatic impairment, chronic concomitant anti-platelet use, and CHA2DS2-VASc score. Results: Overall, 13,164 patients were included, with a median (interquartile range) age of 75.0 (68.0, 80.0) years. Overall annualized intracranial haemorrhage rates were 0.18%/year and remained ≤0.24%/year in high-risk subpopulations, with minor rate increases observed with age (<65 years: 0.07%/year, ≥65–<75 years: 0.16%/year, ≥75 years: 0.23%/year) and CHA2DS2-VASc score (0–1: 0.04%/year, 2–4: 0.19%/year, >4: 0.24%/year). Overall annualized haemorrhagic stroke rates were 0.08%/year and remained ≤0.10%/year in high-risk subpopulations, with minor rate increases observed with age (<65 years: 0.06%/year, ≥65–<75 years: 0.08%/year, ≥75 years: 0.09%/year) and CHA2DS2-VASc score (0–1: 0.00%/year, 2–4: 0.09%/year, >4: 0.10%/year). Overall annualized ischaemic stroke rates were 0.49%/year and remained ≤1.05%/year in high-risk subpopulations; however, rates increased notably with age (<65 years: 0.21%/year, ≥65–<75 years: 0.34%/year, ≥75 years: 0.68%/year) and CHA2DS2VASc score (0–1: 0.15%/year, 2–4: 0.43%/year, >4: 1.05%/year). Conclusions: Annualized intracranial haemorrhage, haemorrhagic stroke, and ischaemic stroke rates in ETNA-AF-Europe were low and demonstrated no meaningful increases with renal/hepatic impairment and chronic concomitant antiplatelet use. Minor rate increases observed with higher CHA2DS2-VASc scores and increasing age were much less steep for haemorrhagic stroke than for ischaemic stroke.