Rivaroxaban Versus Aspirin in Secondary Prevention of Stroke and Prevention of Systemic Embolism in Patients With Recent Embolic Stroke of Undetermined Source (ESUS)

Major bleeding event (as per ISTH), defined as bleeding event that met at least one of following: fatal bleeding; symptomatic bleeding in a critical area or organ (intraarticular, intramuscular with compartment syndrome, intraocular, intraspinal, pericardial, or retroperitoneal); symptomatic intracranial haemorrhage; clinically overt bleeding associated with a recent decrease in the hemoglobin level of greater than or equal to (\>=) 2 grams per decilitre (g/dL) (20 grams per liter \[g/L\]; 1.24 millimoles per liter \[mmol/L\]) compared to the most recent hemoglobin value available before the event; clinically overt bleeding leading to transfusion of 2 or more units of packed red blood cells or whole blood. The results were based on classification of events that have been positively adjudicated as major bleeding events. Incidence rate estimated as number of subjects with incident events divided by cumulative at-risk time, where subject is no longer at risk once an incident event occurred.

Time frame: From randomization until the efficacy cut-off date (median 326 days)

Population: Intention-to-treat analysis set included all randomized participants. Participants who were evaluable for this measure at given time period for the arm were included in the category.

Components of composite efficacy outcome (adjudicated) includes stroke (ischemic, hemorrhagic, and undefined stroke, TIA with positive neuroimaging) and systemic embolism. Incidence rate estimated as number of participants with incident events divided by cumulative at-risk time, where participant is no longer at risk once an incident event occurred.

Time frame: From randomization until the efficacy cut-off date (median 326 days)

Population: Intention-to-treat analysis set included all randomized participants. Participants who were evaluable for this measure at given time period for the arm were included in the category.

All-cause mortality includes all deaths of participants due to any cause.

Time frame: From randomization until the efficacy cut-off date (median 326 days)

Population: Intention-to-treat analysis set included all randomized participants. Participants who were evaluable for this measure at given time period for the arm were included in the category.

Incidence rate estimated as number of participants with incident events divided by cumulative at-risk time, where participant is no longer at risk once an incident event occurred. Cardiovascular death includes death due to hemorrhage and death with undetermined/unknown cause. Systemic embolism is defined as abrupt vascular insufficiency associated with clinical or radiological evidence of arterial occlusion in the absence of other likely mechanisms. The diagnosis of myocardial infarction requires the combination of: 1)evidence of myocardial necrosis (either changes in cardiac biomarkers or post-mortem pathological findings); and 2)supporting information derived from the clinical presentation, electrocardiographic changes, or the results of myocardial or coronary artery imaging.

Time frame: From randomization until the efficacy cut-off date (median 326 days)

Population: Intention-to-treat analysis set included all randomized participants. Participants who were evaluable for this measure at given time period for the arm were included in the category.

Non-major clinically relevant bleeding was defined as non-major overt bleeding but required medical attention (example: hospitalization, medical treatment for bleeding), and/or was associated with the study drug interruption of more than 14 days. The results were based on the outcome events at or after randomization until the efficacy cut-off date. Incidence rate estimated as number of participants with incident events divided by cumulative at-risk time, where participant is no longer at risk once an incident event occurred.

Time frame: From randomization until the efficacy cut-off date (median 326 days)

Population: Intention-to-treat analysis set included all randomized participants. Participants who were evaluable for this measure at given time period for the arm were included in the category.

Intracranial hemorrhage included all bleeding events that occurred in intracerebral, sub arachnoidal as well as subdural or epidural sites. The below table displays results for all randomized participants and the outcomes at or after randomization until the efficacy cut-off date. Incidence rate estimated as number of participants with incident events divided by cumulative at-risk time, where participant is no longer at risk once an incident event occurred.

Time frame: From randomization until the efficacy cut-off date (median 326 days)

Population: Intention-to-treat analysis set included all randomized participants. Participants who were evaluable for this measure at given time period for the arm were included in the category.

Life-threatening bleeding was defined as a subset of major bleeding that met at least one of the following criteria: 1) fatal bleeding; 2) symptomatic intracranial haemorrhage; 3) reduction in hemoglobin of at least 5 g/dl (50 g/l; 3.10 mmol/L); 4) transfusion of at least 4 units of packed red cells or whole blood; 5) associated with hypotension requiring the use of intravenous inotropic agents; 6) necessitated surgical intervention. Incidence rate estimated as number of participants with incident events divided by cumulative at-risk time, where participant is no longer at risk once an incident event occurred.

Time frame: From randomization until the efficacy cut-off date (median 326 days)

Population: Intention-to-treat analysis set included all randomized participants. Participants who were evaluable for this measure at given time period for the arm were included in the category.

Disabling stroke is defined as stroke with modified Rankin score (mRS) greater than or equal to (\>=) 4 as assessed by investigator. mRS spans 0-6, running from perfect health to death. A score of 0-3 indicates functional status ranging from no symptoms to moderate disability (defined in the mRS as requiring some help, but able to walk without assistance); mRS 4-6 indicates functional status ranging from moderately severe disability (unable to walk or to attend to own bodily needs without assistance)through to death. CV death includes death due to hemorrhage and death with undetermined/unknown cause. Diagnosis of myocardial infarction requires combination of: 1) evidence of myocardial necrosis either changes in cardiac biomarkers or post-mortem pathological findings); 2) supporting information derived from clinical presentation, electrocardiographic changes, or results of myocardial or coronary artery imaging.

Time frame: From randomization until the efficacy cut-off date (median 326 days)

Population: Intention-to-treat analysis set included all randomized participants. Participants who were evaluable for this measure at given time period for the arm were included in the category.