The present trial is addressing the question if a biologically distinct subgroup of ischemic stroke patients without known atrial fibrillation at admission, selected by a cut-off level of MRproANP concentration, which represents a underlying increased risk of cardiac thrombogenicity, benefits from direct oral anticoagulation (DOAC) within 7 days of symptom onset versus standard of care (antiplatelet) as preventive treatment.

Three DOACs with marketing authorisation in Switzerland and the EU for the prevention of stroke and systemic embolism in patients with atrial fibrillation can be used. Eligible patients will be randomly assigned to either the standard of care (control) or the experimental (direct start with DOAC) arm with a ratio of 1:1. Each study participant will be observed during a follow up period within one year after index stroke.

Inclusion Criteria:

• Clinical diagnosis of ischemic stroke
• level ≥200pmol/L within 72 hours from symptom onset
• Age ≥ 18 years
• Signed informed consent

Exclusion Criteria:

• History of AF, AF on 12-lead ECG on admission or any AF ≥30 seconds during heart-rhythm monitoring prior to randomization
• Other condition that require anticoagulant therapy (e.g., venous thromboembolism) as per Investigator's judgment including therapeutical dose of low-molecular-weight heparin or heparin
• Strong likelihood to be treated with prolonged (i.e. more than 30 days) dual antiplatelet therapy during the course of the trial (such as coronary stenting, etc.)
• Patients undergoing planned procedures where therapy with a DOAC is a contraindication (e.g. surgery)
• Previous intracranial hemorrhage in the last year
• Evidence of severe cerebral amyloid angiopathy if MRI scan performed
• Chronic kidney disease with creatinin clearance <30ml/min and or subject who requires haemodialysis or peritoneal dialysis
• Known bleeding diathesis (e.g. active peptic ulcer disease , platelet count < 100'000/mm3 or haemoglobin < 9 g/dl or INR ≥ 1.7, documented haemorrhagic tendencies or blood dyscrasias)
• Active infective endocarditis
• CT or MRI evidence of cerebral vasculitis
• Known allergy or intolerance to antiplatelets or DOACs
• Female who is pregnant or lactating or has a positive pregnancy test at time of admission
• Current participation in another drug trial

Blinded endpoint assessment by independent CEC