SIMPLAAFY Clinical Trial

Inclusion Criteria:

* Subject is of legal age to participate in the study per the laws of their respective geography.
* Subject is an acceptable candidate for a WATCHMAN FLX Pro device per the approved Instructions for Use.
* Subject is deemed to be suitable for all protocol defined drug regimens in the control and both test arms.
* The subject or legal representative is able to understand and willing to provide written informed consent to participate in the trial.
* The subject is able and willing to return for required follow-up visits and examinations.

Exclusion Criteria:

* Subject's device implant procedure was aborted (i.e., failed implant).
* Subject has a device margin residual leak \> 0mm at time of implant.
* Occurrence of complications (major bleeding, systemic embolism, stroke, pericardial effusion requiring intervention) during the implant procedure, post-procedure, or prior to randomization.
* Subject has a contraindication to one of the three protocol defined drug regimens.
* Subject requires long-term anticoagulation therapy for reason other than AF-related stroke risk reduction or requires chronic P2Y12 inhibitor therapy.
* Subject has known history of severe liver disease including cirrhosis with a Child-Pugh classification C or D.
* Subject with known hypercoagulability disorder, mechanical heart valve, rheumatic heart disease, or recurrent deep vein thrombosis.
* Subject has intracardiac thrombus, LAA sludge, or dense spontaneous echo contrast (SEC) observed during pre-implant imaging.
* Subject has Modified Rankin Score of ≥ 3 at baseline.
* Subject has left ventricular ejection fraction (LVEF) \< 30%.
* Subject with known amyloid cardiomyopathy.
* Platelet count ≤ 100,000 x 109/L.
* Subject has an estimated glomerular filtration rate (eGFR) \< 30 ml/min (chronic kidney disease stage IV or V) or is on dialysis.
* Subject has a stroke (of any cause, whether ischemic or hemorrhagic) within 30 days prior to implant or prior to randomization.
* Subject has a documented myocardial infarction (MI) as either a non-ST elevation MI (NSTEMI) or as an ST-elevation MI (STEMI), with or without intervention, within 30 days prior to implant or prior to randomization.
* Subject had or is planning to have any cardiac or non-cardiac intervention or surgical procedure within 30 days prior to or 6-months after implant (including, but not limited to, cardioversion, percutaneous coronary intervention, cardiac ablation, cataract surgery, etc.).
* Subject has a major bleeding event per International Society on Thrombosis and Haemostasis (ISTH) definitions within the 30 days prior to implant or prior to randomization. Lack of resolution of related clinical sequelae or planned and pending interventions to resolve bleeding/bleeding source are a further exclusion regardless of timing of the bleeding event.
* Subject has an active bleed.
* Subject has a cardiac tumor.
* Subject has signs/symptoms of acute or chronic pericarditis.
* Subject has an active infection.
* There is evidence of tamponade physiology.
* Subject has New York Heart Association Class IV congestive heart failure at the time of implant or prior to randomization.
* Subject is currently enrolled in another investigational study, except if the subject is participating in a mandatory governmental registry, or a purely observational registry with no associated treatment.
* Subject is of childbearing potential and is, or plans to become, pregnant during the time of the study.
* Subject has a documented life expectancy of less than 12 months.