The trial was terminated at the planned interim analysis for futility on July 18, 2023.

The Purpose of this open-label randomized controlled multicenter trial is to evaluate the efficacy and safety of mono-drug therapy with oral anticoagulant compared to combination therapy with antiplatelet drug, in ischemic stroke patients with non-valvular atrial fibrillation and atherothrombosis.

The Purpose of this open-label randomized controlled multicenter trial is to evaluate the efficacy and safety of mono-drug therapy with oral anticoagulant compared to combination therapy with antiplatelet drug, in ischemic stroke patients with non-valvular atrial fibrillation and atherothrombosis. Target sample size is 400. The primary outcome is a composite endpoint of ischemic cardiovascular events (cardiovascular death, ischemic stroke, myocardial infarction, systemic embolism, ischemic events requiring urgent revascularization) and major bleeding defined by the International Society on Thrombosis and Haemostasis(ISTH) criteria within 2 years after randomization.

Inclusion Criteria:

1. Patients with an acute ischemic stroke or TIA from 8 days and up to 360 days from the onset of symptoms

2. Age 20 or older

3. Patients with non-valvular atrial fibrillation (chronic or paroxysmal) who start or continue taking an oral anticoagulant

4. Patients who have one of the following atherothrombotic diseases

   1. A past history of ischemic heart disease (myocardial infarction, angina pectoris, coronary artery bypass graft (CABG), percutaneous coronary intervention (PCI)
   2. A past history of peripheral artery disease (symptomatic peripheral arterial occlusive disease, lower extremity bypass surgery/angioplasty/stenting)
   3. Carotid artery stenosis (symptomatic or asymptomatic (=>50% diameter), a history of carotid artery stenting (CAS) or carotid endarterectomy (CEA))
   4. Intracranial artery stenosis (=>50% stenosis of the diameter of a major intracranial artery: intracranial internal carotid artery, anterior cerebral artery (ACA)-A1 and A2, middle cerebral artery (MCA)-M1 and M2, posterior cerebral artery (PCA)-P1 and P2, vertebral artery, and basilar artery; a history of intracranial stent placement or intracranial bypass surgery)
   5. A past history of atherothrombotic brain infarction, lacunar infarction, or branch atheromatous disease

5. Patients without severe disability (modified Rankin Scale score =<4)

6. Patients who can take oral medications

7. Patients who can receive follow-up survey

8. Provision of written informed consent either directly or by a suitable surrogate

Exclusion Criteria:

1. History of myocardial infarction or acute coronary syndrome within the past 12 months
2. Patients who underwent PCI with drug-eluting stents within the past 12 months or PCI with bare-metal stents within the past 3 months
3. Patients who underwent carotid artery stent placement, intracranial stent placement, or lower extremity stent placement within the past 3 months
4. History of symptomatic intracranial hemorrhage or gastrointestinal bleeding within the past 6 months
5. Hemorrhagic diathesis or blood coagulation disorders
6. Platelet counts <100,000 /mm3 at enrollment.
7. Severe anemia (hemoglobin <7 g/dL)
8. Severe renal failure (creatinine clearance =<15 mL/min) or undergoing chronic hemodialysis.
9. Severe liver dysfunction (Grade B or C of the Child-Pugh classification)
10. Patients with severe disability requires constant nursing care, bedridden (modified Rankin Scale score =5)
11. Pregnant or possibly pregnant women
12. Active cancer
13. Expectation of survival less than 2 years
14. Anticoagulant or antiplatelet is scheduled to be discontinued for more than 4 weeks during the follow-up period
15. Planned revascularization procedure during the follow-up period
16. Patients who are enrolled in other trials
17. Patients judged as inappropriate for this study by investigators