Key Inclusion Criteria:
- Has AF or flutter (paroxysmal or persistent), not felt to be secondary to a reversible cause, and an indication for indefinite anticoagulation treatment as described in the protocol
- Meets one of the following:
- CHA2DS2-VA [C: Congestive heart failure; H: Hypertension; A2: Age ≥75 years (double points); D: Diabetes mellitus; S2: Stroke or TIA or Thromboembolism (double points); V: Vascular disease; A: Age 65-74 years] score ≥2 and Oral Anticoagulant (OAC) naïve or
- CHA2DS2-VA score ≥3 or
- CHA2DS2-VA score of 2 and at least 1 enrichment criteria as described in the protocol
- Must have a Prothrombin Time/International Normalization Ratio (PT/INR) <2.5 at the time of randomization if taking warfarin or another Vitamin K Antagonist (VKA)
Key Exclusion Criteria:
- Has a mechanical heart valve prosthesis (Note: transcatheter aortic valve replacement is not an exclusion)
- Has known moderate-to-severe mitral stenosis
- Has had successful ablation therapy or Left Atrial Appendage (LAA) occlusion/exclusion, or planned ablation or LAA occlusion/exclusion as described in the protocol
- Had an ischemic stroke within 2 days prior to randomization
- Has Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) estimated Glomerular Filtration Rate (eGFR) <15 mL/min/1.73m^2 within 14 days prior to randomization or on dialysis or expected to be started as described in the protocol
- Has a history of central nervous system bleeding within 30 days prior to randomization
Note: Other protocol-defined Inclusion/ Exclusion criteria apply