EdoxabaN for IntraCranial Hemorrhage Survivors with Atrial Fibrillation (ENRICH-AF)

Inclusion Criteria:

1. Written informed consent provided

2. Age ≥45 years, at the time of signing the informed consent

3. Previous intracranial hemorrhage (symptomatic, spontaneous and non-traumaticnon-lobar intraparenchymal or intraventricular hemorrhage, and symptomaticspontaneous or non-penetrating traumatic subdural hemorrhages) on or offantithrombotic therapy

4. Documented atrial fibrillation (paroxysmal, persistent, permanent)

5. CHA2DS2-VASc score ≥2

Exclusion Criteria:

1. Recent intracranial hemorrhage (within 14 days)

2. Secondary macrovascular, neoplastic or infectious causes of intracranial hemorrhage (except for antithrombotic treatment or non-penetrating traumatic subduralhemorrhages)

3. Isolated subarachnoid hemorrhage (convexity or basal); subarachnoid blood trackingonto convexity secondary to an intraventricular hemorrhage or as part of amulticompartment bleed in cases of traumatic subdural hemorrhages are eligible

4. Need for ongoing oral anticoagulant therapy for indication other than AF (e.g.mechanical heart valve, venous thromboembolic disease)

5. Need for ongoing antiplatelet therapy for indication where edoxaban would not be asuitable substitute

6. Plans for left atrial appendage occlusion

7. Estimated creatinine clearance (CrCl) < 15 mL/min

8. Platelet count less than 100,000mm3 at enrollment or other bleeding diathesis

9. Persistent, uncontrolled hypertension (systolic BP averaging >150 mmHg)

10. Chronic use of NSAID

11. Clinically significant active bleeding, including gastrointestinal bleeding

12. Lesions or conditions at increased risk of clinically significant bleeding, e.g.active peptic ulcer disease with recent bleeding, patients with spontaneous oracquired impairment of hemostasis

13. Antiphospholipid antibody syndrome

14. Hepatic disease associated with coagulopathy and clinically relevant bleeding risk

15. Known hypersensitivity to edoxaban

16. Estimated inability to adhere to study procedures

17. Pregnancy or breastfeeding

18. Estimated life expectancy < 6 months at the time of enrollment

19. Close affiliation with the investigational site; e.g. a close relative for theinvestigator, dependent person (e.g., employee or student of the investigationalsite)

20. Lobar intraparenchymal hemorrhage

• Post menopausal female subjects must be amenorrheic for ≥12 months prior toscreening or ≥6 weeks post-surgical bilateral oophorectomy (with or withouthysterectomy) prior to screening. Women of childbearing potential must havenegative serum pregnancy test within 7 days prior to randomization or urinepregnancy testing within 24 hours of randomization. Heterosexually active womenof childbearing potential must use highly effective methods of contraceptionfor 32 days after discontinuation (duration of study drug plus 30 days durationof one ovulatory cycle).