• Recruitment of the target population within 2 years [ Time Frame: 2 years from start of trial ]
• At least 80% of randomized participants remain in the trial and on the allocated study treatment at the end of the 26-week study period. [ Time Frame: 26 weeks ]

• Proportion of patients randomized to warfarin achieving a Time in the Therapeutic Range (TTR) >65%. [ Time Frame: 26 weeks ]
• >95% of randomized patients adhere to the enrollment criteria with respect to atrial fibrillation or atrial flutter [ Time Frame: End of trial ]
  Through adjudication of ECGs or other cardiac diagnostics
• Major bleeding [ Time Frame: 26 weeks ]
  As defined by the International Society of Thrombosis and Haemostasis (ISTH)
• Clinically relevant non-major bleeding [ Time Frame: 26 weeks ]
  As defined by the International Society of Thrombosis and Haemostasis (ISTH)
• Stroke and systemic embolism [ Time Frame: 26 weeks ]
• All cause mortality [ Time Frame: 26 weeks ]
• Non-fatal myocardial infarction [ Time Frame: 26 weeks ]
• Vascular events not related to dialysis access [ Time Frame: 26 weeks ]
• Events of special interest related to dialysis access, the dialysis procedure or the oral anticoagulants [ Time Frame: 26 weeks ]
  Thrombosis of fistula or graft; fistula or graft abandonment; thrombosis of dialysis catheter; red blood cell transfusions; calciphylaxis

• Time in the Therapeutic Range [ Time Frame: 26 weeks ]
  Proportion of patients randomized to warfarin achieving a Time in the Therapeutic Range (TTR) >65%.
• >95% of enrolled patients meet enrollment criteria with respect to atrial fibrillation [ Time Frame: End of trial ]
  Through adjudication of ECGs or other cardiac diagnostics
• Major bleeding [ Time Frame: 26 weeks ]
  As defined by the International Society of Thrombosis and Haemostasis (ISTH)
• Clinically relevant non-major bleeding [ Time Frame: 26 weeks ]
  As defined by the International Society of Thrombosis and Haemostasis (ISTH)
• Stroke and systemic embolism [ Time Frame: 26 weeks ]
• All-cause mortality, [ Time Frame: 26 weeks ]
• Non-fatal myocardial infarction [ Time Frame: 26 weeks ]
• Vascular events not related to dialysis access [ Time Frame: 26 weeks ]
• Events of special interest related to dialysis access, the dialysis procedure or the oral anticoagulants [ Time Frame: 26 weeks ]
  Thrombosis of fistula or graft; fistula or graft abandonment; thrombosis of dialysis catheter; red blood cell transfusions; calciphylaxis

• Atrial Fibrillation
• End Stage Renal Failure on Dialysis

• Drug: Warfarin
  Individuals randomized to this arm will be exposed to dose-adjusted daily warfarin targeting an international normalized ratio (INR) of 2.0-3.0.
  Other Name: Coumadin
• Drug: Apixaban
  Individuals randomized to this arm will receive apixaban 5 mg twice daily (a reduced dose of 2.5 mg twice daily will be given to selected participants).
  Other Name: Eliquis
• Other: No oral anticoagulation
  No oral anticoagulation

• Experimental: Warfarin
  Individuals randomized to this arm will be exposed to dose-adjusted daily warfarin targeting an international normalized ratio (INR) of 2.0-3.0.
  Intervention: Drug: Warfarin
• Active Comparator: Apixaban
  Individuals randomized to this arm will receive apixaban 5 mg twice daily (a reduced dose of 2.5 mg twice daily will be given to selected participants).
  Intervention: Drug: Apixaban
• Active Comparator: No oral anticoagulation
  Individuals in this arm will be exposed to a treatment strategy in which no oral anticoagulation is prescribed.
  Intervention: Other: No oral anticoagulation

Inclusion Criteria:

1. Age ≥ 18 years.
2. Receiving maintenance hemodialysis or peritoneal dialysis for > 90 days.

3. History of AF or atrial flutter as defined by:

   (i) AF or atrial flutter on a 12 lead ECG at enrollment, and not due to a reversible cause, or (ii) AF or atrial flutter documented on two separate occasions, not due to a reversible cause, at least 1 day apart prior to enrollment. AF or atrial flutter may be documented by ECG, or as an episode lasting at least 30 seconds on a rhythm strip or Holter recording, or more than 30 minutes if using pacemaker or implantable cardioverter defibrillator (ICD) recordings, or (iii) AF or atrial flutter documented on one occasion, not due to a reversible cause, prior to enrollment and being treated with an oral anticoagulant for AF or atrial flutter at enrollment. [AF or atrial flutter may be documented by ECG, or as an episode lasting at least 30 seconds on a rhythm strip or Holter recording, or more than 30 minutes if using pacemaker or implantable cardioverter defibrillator (ICD) recordings, or mentioned in the medical record], or (iv) AF or atrial flutter documented on one occasion on ECG, not due to a reversible cause, prior to enrollment and at least one more episode of AF or atrial flutter mentioned in the medical record, or (v) AF or atrial flutter documented on one occasion in a cardiologist report, not due to a reversible condition, prior to enrollment.

4. Satisfying CHADS-65 criteria: i) Age ≥65 or ii) Age <65 and one of: hypertension, diabetes mellitus, congestive heart failure, stroke/transient ischemic attack or peripheral embolism.

Exclusion Criteria:

1. Moderate or severe mitral stenosis.
2. Conditions other than non-valvular atrial fibrillation that require oral anticoagulation, such as mechanical prosthetic valve, deep venous thrombosis, or pulmonary embolism.
3. Need for aspirin at a dose > 165 mg a day, or need for aspirin in combination with P2Y12 antagonist therapy.
4. Need for an interacting drug which precludes the safe use of apixaban.
5. Life expectancy < 6 months.
6. Scheduled live-donor kidney transplant in the next 6 months.
7. A woman who is pregnant or breastfeeding or unwilling to pursue methods of contraception if < 12 months since the last menstrual period.
8. Co-enrollment in a clinical trial where the intervention is deemed to interfere with the adherence, safety or efficacy of the intervention provided herein.
9. Patient's attending physician(s) (e.g., nephrologist and/or cardiologist and/or neurologist) believes that oral anticoagulation is absolutely mandated.
10. Patient's attending physician(s) (e.g., nephrologist and/or cardiologist and/or neurologist) believes that oral anticoagulation is absolutely contraindicated.

• Canadian Institutes of Health Research (CIHR)
• The George Institute for Global Health (Sydney, Australia)