An Efficacy and Safety Study of Rivaroxaban With Warfarin for the Prevention of Stroke and Non-Central Nervous System Systemic Embolism in Patients With Non-Valvular Atrial Fibrillation

• The Composite Event of Stroke/Non-CNS Systemic Embolism: Primary Efficacy (Non-Inferiority) [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
  The number of patients with the first occurrence of a stroke or non-CNS systemic embolism while on treatment (defined as the time interval from the first dose to the last dose of study drug plus 2 days). The statistical analysis is based on time from randomization to the first occurrence of the event while on treatment.
  
  
• The Composite of Event of Stroke/Non-CNS Systemic Embolism: Primary Efficacy (Superiority) [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
  The number of patients with the first occurrence of a stroke or non-CNS systemic embolism while on treatment (defined as the time interval from the first dose to the last dose of study drug plus 2 days). The statistical analysis is based on time from randomization to the first occurrence of the event while on treatment.
  
  
• The Composite Event of Major/Non-major Clinically Relevant Bleeding Events: Primary Safety [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
  The number of patients with the first occurrence of a major or non-major clinically relevant bleeding event while on treatment. The statistical analysis is based on time from the first dose of study drug to the first occurrence of the event while on treatment.
  
  

• The Composite Event of Stroke/Non-CNS Systemic Embolism/Vascular Death [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
  The number of patients with the first occurrence of a stroke, non-CNS systemic embolism, or vascular death while on treatment. The statistical analysis is based on time from randomization to the first occurrence of the event while on treatment.
  
  
• The Composite Event of Stroke/Non-CNS Systemic Embolism/Myocardial Infarction/Vascular Death [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
  The number of patients with the first occurrence of a stroke, non-CNS systemic embolism, myocardial infarction, or vascular death while on treatment. The statistical analysis is based on time from randomization to the first occurrence of the event while on treatment.
  
  
• The Individual Components of the Composite Primary and Major Secondary Efficacy Outcome Measures: Stroke [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
  The number of patients with the first occurrence of a stroke while on treatment. The statistical analysis is based on time from randomization to the first occurrence of the event while on treatment.
  
  
• The Individual Components of the Composite Primary and Major Secondary Efficacy Outcome Measures: Non-CNS Systemic Embolism [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
  The number of patients with the first occurrence of a non-CNS systemic embolism while on treatment. The statistical analysis is based on time from randomization to the first occurrence of the event while on treatment.
  
  
• The Individual Components of the Composite Primary and Major Secondary Efficacy Outcome Measures: Myocardial Infarction [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
  The number of patients with the first occurrence of a myocardial infarction while on treatment. The statistical analysis is based on time from randomization to the first occurrence of the event while on treatment.
  
  
• The Individual Components of the Composite Primary and Major Secondary Efficacy Outcome Measures: Vascular Death [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
  The number of patients with the occurrence of vascular death while on treatment. The statistical analysis is based on time from randomization to the event while on treatment.
  
  
• All-cause Mortality [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
  The number of patients who died due to any cause while on treatment. The statistical analysis is based on time from randomization to the event while on treatment.
  
  

Patients with non-valvular atrial fibrillation who are at risk for stroke and non-central nervous system (non-CNS) systemic embolism, will be randomized (assigned by chance) to receive treatment with rivaroxaban or warfarin, two different anticoagulants (substances that prevent blood clots). Treatment will be double-blinded (neither the patient nor study staff will know which study drug is assigned to patients during the study). Patients assigned to rivaroxaban will receive rivaroxaban 20 mg orally (p.o.) once daily (OD) plus warfarin placebo p.o. OD titrated to a target sham international normalized ratio (INR) of 2.5. Patients with moderate renal impairment at screening will receive rivaroxaban 15 mg p.o. OD. Patients assigned to warfarin will receive warfarin p.o. OD titrated to a target INR of 2.5 plus rivaroxaban placebo p.o. OD. The maximum expected length of treatment is up to 32 months but may be extended up to 4 years.