Oral Anticoagulation Versus Left Atrial Appendage Occlusion Added to Direct Oral Anticoagulation in Patients with Stroke Despite Oral

Inclusion Criteria:

• Cardioembolic* Ischemic stroke despite OAC or DOAC within the last 6 months.

• Documented AF (either valvular or non-valvular AF).

• LAA suitable for closure (if LAA thrombus, just distal).

• Functional status at inclusion with no severe disability (mRS<4).

• No contraindication for LAA assessment by CT or 3D-TEE.

• >18 years

• Life expectancy >1year

• Able to understand written consent prior to the trial inclusion.

• Able and willing to return for follow-up visits and tests.

Exclusion Criteria:

• Absolute contraindication to OAC/DOAC.

• Non-compliance of OAC/DOAC >24 hours within the last week before the index stroke (>1 dose per - - Antagonist Vit K and >2 doses per DOAC).

• Lacunar Ischemic Stroke.

• Symptomatic carotid disease (defined as > 50% lumen diameter narrowing on CTA, MRA,or TCD with symptoms of ipsilateral transient or visual TIA evidenced by amaurosisfugax, ipsilateral hemispheric TIAs or ipsilateral stroke); if subject has a historyof carotid stent or endarterectomy the subject is eligible if there is < 50% lumendiameter narrowing.

• Planned cardiac intervention or surgery, which is invasive or requires sedation oranesthesia, within 3 months following randomization, other than study-relatedprocedures such as LAAO and cardiac imaging (if applicable).

• In the opinion of the investigator, is considered at high risk for generalanesthesia and general anesthesia is planned for the study procedure.

• Non-treated patent foramen ovale (PFO) or PFO closure device implanted.

• Inferior vena cava filter.

• Has any of the customary contraindications for a percutaneous catheterizationprocedure (e.g. subject is too small to accommodate the ICE probe (if planned) orrequired catheters, or subject has - active infection or bleeding disorder).

• Customary contraindications for TEE/TOE (e.g., presence of esophageal varices,esophageal stricture, or history of esophageal cancer).

• Underwent catheter ablation for AF or atrial flutter within 60 days prior torandomization.

• Experienced myocardial infarction within 90 days prior to randomization.

• New York Heart Association Class IV Congestive Heart Failure.

• Left ventricular ejection fraction ≤ 30% (per most recent assessment).

• LAA is obliterated or surgically ligated.

• Thrombocytopenia (defined as < 50,000 platelets per microliter (<50 x 109/L) oranemia (defined as hemoglobin < 10 g/dL) requiring transfusions.

• Hypersensitivity to any portion of the device material or individual components ofthe Amulet LAA occluder device (e.g., nickel allergy).

• Allergy to contrast media if the patient needs angio-CT and cannot undergo TEE/TOE.

• Actively enrolled in, or plans to enroll in, a concurrent clinical study in whichthe active treatment arm may confound the results of this trial.

• Is pregnant or breastfeeding, or pregnancy is planned during the course of theinvestigation.

• Active endocarditis or other infection producing bacteremia.

• Presence of other anatomic or comorbid conditions, or other medical, social, orpsychological conditions that, in the Investigator's opinion, could limit thesubject's ability to participate in clinical investigation or to comply with followup requirements, or impact the scientific soundness of the clinical investigationresults.