Safety and Effectiveness of Apixaban Compared to Warfarin in Secondary Prevention in Patients With Atrial Fibrillation

Safety and Effectiveness of Apixaban Compared to Warfarin in Secondary Prevention in Patients With NVAF With a History of Stroke or Transient Ischemic Attack - a Nationwide Retrospective Observational Study Using Claims Data in Japan

Status

Completed

Phases

Unknown

Study type

Observational

Source

ClinicalTrials.gov

Registry ID

NCT05321810

Enrollment

193565

Registered

2022-04-11

Start date

2022-04-15

Completion date

2022-04-15

Last updated

2024-01-11

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Non-valvular Atrial Fibrillation

Keywords

Non-valvular atrial fibrillation, Stroke, Apixaban, Warfarin, Secondary prevention

Brief summary

The purpose of this study are 1) to characterize the primary and secondary prevention patients, 2) to calculate incidence rates of stroke/SE or major bleeding in each cohort and 3) to investigate for Japanese secondary prevention patients as Real World Evidence (RWE) on the effectiveness and safety of apixaban compared to warfarin in patients with non-valvular atrial fibrillation (NVAF).

Detailed description

Japanese population has shown to have higher rate of incidence of stroke and stroke mortality is also higher. Patients with a history of ischemic stroke are at high risk of recurrence and require more rigorous management to prevent recurrence. The same is true for patients with non-valvular atrial fibrillation (NVAF) and treatment with anticoagulants reduces the risk of recurrent embolic stroke. However, some patients still suffer from recurrent embolic and/or ischemic stroke even if they are on anticoagulants for secondary prevention. In addition to the recurrent stroke, risk of bleeding is also higher in the patients with a history of stroke because they are often chronically treated with antiplatelet agents to prevent recurrence after cerebral infarction and with an anticoagulant after embolic stroke. Concomitant use of anticoagulant and anti-platelet agents is sometimes necessary if patients with AF experience cerebral infarction and the risk of bleedings largely enhances in these patients. Thus, patients in secondary prevention are at higher risk of both recurrent ischemic stroke and more effective and safer antithrombotic therapy should take this into account. The purpose of this study are 1) to characterize the primary and secondary prevention patients, 2) to calculate incidence rates of stroke/SE or major bleeding in each cohort and 3) to investigate for Japanese secondary prevention patients as RWE on the effectiveness and safety of apixaban compared to warfarin in patients NVAF.

Interventions

DRUGApixaban

This is observational study and the patients in the apixaban cohort include those who are exposed to apixaban in the real world settings.

DRUGWarfarin

This is observational study and the patients in the warfarin cohort include those who are exposed to warfarin in the real world settings.

Study design

Observational model

COHORT

Time perspective

RETROSPECTIVE

Eligibility

Sex/Gender

ALL

Age

20 Years to No maximum

Healthy volunteers

Inclusion criteria

Patients must meet all the following selection criteria 1. Patients registered in the Medical Data Vision (MDV) database 2008 though 2021. 2. Patients newly with non-valvular atrial fibrillation 3. Patients who newly receive warfarin or apixaban after diagnosis of NVAF 4. Age 20 years or older on the index date 5. Patients who have a history of stroke or transient ischemic attack (TIA) are inclusion criteria only for secondary prevention cohort, otherwise patients will be concluded in the primary prevention cohort.

Exclusion criteria

Patients who meet the following

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants With Risk of Major Bleeding at 24 Months: Secondary Prevention (Balanced) Cohorts	24 months	In this outcome measure, number of participants with risk of major bleeding at 24 months was reported. Major bleeding, was defined as any bleeding which required hospitalization for treatment (the primary reason for the hospitalization was to treat the bleeding).
Number of Participants With Risk of a Composite of Recurrent Stroke or SE at 0 Month: Secondary Prevention (Balanced) Cohorts	0 month	In this outcome measure, number of participants with risk of a composite of recurrent stroke (ischemic and hemorrhagic stroke)/SE at 0 month was reported. Recurrent meant once participants were discharged from the hospital and became outpatients and then rehospitalized due to stroke or SE.
Number of Participants With Risk of a Composite of Recurrent Stroke or SE at 6 Months: Secondary Prevention (Balanced) Cohorts	6 months	In this outcome measure, number of participants with risk of a composite of recurrent stroke (ischemic and hemorrhagic stroke)/SE at 6 months was reported. Recurrent meant once participants were discharged from the hospital and became outpatients and then rehospitalized due to stroke or SE.
Number of Participants With Risk of a Composite of Recurrent Stroke or SE at 12 Months: Secondary Prevention (Balanced) Cohorts	12 months	In this outcome measure, number of participants with risk of a composite of recurrent stroke (ischemic and hemorrhagic stroke)/SE at 12 months was reported. Recurrent meant once participants were discharged from the hospital and became outpatients and then rehospitalized due to stroke or SE.
Number of Participants With Risk of a Composite of Recurrent Stroke or SE at 18 Months: Secondary Prevention (Balanced) Cohorts	18 months	In this outcome measure, number of participants with risk of a composite of recurrent stroke (ischemic and hemorrhagic stroke)/SE at 18 months was reported. Recurrent meant once participants were discharged from the hospital and became outpatients and then rehospitalized due to stroke or SE.
Number of Participants With Risk of a Composite of Recurrent Stroke or SE at 24 Months: Secondary Prevention (Balanced) Cohorts	24 months	In this outcome measure, number of participants with risk of a composite of recurrent stroke (ischemic and hemorrhagic stroke)/SE at 24 months was reported. Recurrent meant once participants were discharged from the hospital and became outpatients and then rehospitalized due to stroke or SE.
Incidence Rate of Major Bleeding During the Follow-up Period: Secondary Prevention (Balanced) Cohorts	During follow up period (Data collected between 2008 to 2021 [approximately 13 years])	Incidence rate was reported as events per 1,000 participant-years. First occurrence of major bleeding after index date during the follow-up period was considered. Major bleeding, was defined as any bleeding which required hospitalization for treatment (the primary reason for the hospitalization was to treat the bleeding). Index date was defined as the next day of the day when participants diagnosed with NVAF initiated warfarin or apixaban. The follow up period was the period until the first observation of the earlier of the following from index date: until discontinuation of index OAC, switch of OAC, lack of records, occurrence of stroke, SE, or hemorrhagic events, or elapsing of 2 years from index date.
Time Course of Proportion of Incidence of Major Bleeding-Free Participants at 0 Month: Secondary Prevention (Balanced) Cohorts	0 month	In this outcome measure, probability of participants being event-free at 0 month was reported, which was estimated by using a Kaplan-Meier method. (Here, event meant major bleeding). Major bleeding, was defined as any bleeding which required hospitalization for treatment (the primary reason for the hospitalization was to treat the bleeding).
Time Course of Proportion of Incidence of Major Bleeding-Free Participants at 6 Months: Secondary Prevention (Balanced) Cohorts	6 months	In this outcome measure, probability of participants being event-free at 6 months was reported, which was estimated by using a Kaplan-Meier method. (Here, event meant major bleeding). Major bleeding, was defined as any bleeding which required hospitalization for treatment (the primary reason for the hospitalization was to treat the bleeding).
Time Course of Proportion of Incidence of Major Bleeding-Free Participants at 12 Months: Secondary Prevention (Balanced) Cohorts	12 months	In this outcome measure, probability of participants being event-free at 12 months was reported, which was estimated by using a Kaplan-Meier method. (Here, event meant major bleeding). Major bleeding, was defined as any bleeding which required hospitalization for treatment (the primary reason for the hospitalization was to treat the bleeding).
Time Course of Proportion of Incidence of Major Bleeding-Free Participants at 18 Months: Secondary Prevention (Balanced) Cohorts	18 months	In this outcome measure, probability of participants being event-free at 18 months was reported, which was estimated by using a Kaplan-Meier method. (Here, event meant major bleeding). Major bleeding, was defined as any bleeding which required hospitalization for treatment (the primary reason for the hospitalization was to treat the bleeding).
Time Course of Proportion of Incidence of Major Bleeding-Free Participants at 24 Months: Secondary Prevention (Balanced) Cohorts	24 months	In this outcome measure, probability of participants being event-free at 24 months was reported, which was estimated by using a Kaplan-Meier method. (Here, event meant major bleeding). Major bleeding, was defined as any bleeding which required hospitalization for treatment (the primary reason for the hospitalization was to treat the bleeding).
Number of Participants With Risk of Major Bleeding at 0 Month: Secondary Prevention (Balanced) Cohorts	0 month	In this outcome measure, number of participants with risk of major bleeding at 0 month was reported. Major bleeding, was defined as any bleeding which required hospitalization for treatment (the primary reason for the hospitalization was to treat the bleeding).
Number of Participants With Risk of Major Bleeding at 6 Months: Secondary Prevention (Balanced) Cohorts	6 months	In this outcome measure, number of participants with risk of major bleeding at 6 months was reported. Major bleeding, was defined as any bleeding which required hospitalization for treatment (the primary reason for the hospitalization was to treat the bleeding).
Number of Participants With Risk of Major Bleeding at 12 Months: Secondary Prevention (Balanced) Cohorts	12 months	In this outcome measure, number of participants with risk of major bleeding at 12 months was reported. Major bleeding, was defined as any bleeding which required hospitalization for treatment (the primary reason for the hospitalization was to treat the bleeding).
Number of Participants With Risk of Major Bleeding at 18 Months: Secondary Prevention (Balanced) Cohorts	18 months	In this outcome measure, number of participants with risk of major bleeding at 18 months was reported. Major bleeding, was defined as any bleeding which required hospitalization for treatment (the primary reason for the hospitalization was to treat the bleeding).
Incidence Rate of a Composite of Recurrent Stroke or Systemic Embolism (SE) During the Follow-up Period: Secondary Prevention (Balanced) Cohort	During follow up period (Data collected between 2008 to 2021 [approximately 13 years])	Incidence rate was reported as events per 1,000 participant-years. First occurrence of recurrent stroke or SE events after index date during the follow-up period were considered. Recurrent meant once participants were discharged from the hospital and became outpatients and then rehospitalized due to stroke or SE. Index date was defined as the next day of the day when participants diagnosed with NVAF initiated warfarin or apixaban. The follow up period was the period until the first observation of the earlier of the following from index date: until discontinuation of index oral anticoagulants (OAC), switch of OAC, lack of records, occurrence of stroke, SE, or hemorrhagic events, or elapsing of 2 years from index date.
Time Course of Proportion of the Incidence of a Composite of Recurrent Stroke or Systemic Embolism (SE)-Free Participants at 0 Month: Secondary Prevention (Balanced) Cohorts	0 month	In this outcome measure, probability of participants being event-free at 0 month was reported, which was estimated by using a Kaplan-Meier method. (Here, event meant recurrent stroke or systemic embolism). Recurrent meant once participants were discharged from the hospital and became outpatients and then rehospitalized due to stroke or SE.
Time Course of Proportion of the Incidence of a Composite of Recurrent Stroke or Systemic Embolism (SE)-Free Participants at 6 Months: Secondary Prevention (Balanced) Cohorts	6 months	In this outcome measure, probability of participants being event-free at 6 months was reported, which was estimated by using a Kaplan-Meier method. (Here, event meant recurrent stroke or systemic embolism). Recurrent meant once participants were discharged from the hospital and became outpatients and then rehospitalized due to stroke or SE.
Time Course of Proportion of the Incidence of a Composite of Recurrent Stroke or Systemic Embolism (SE)-Free Participants at 12 Months: Secondary Prevention (Balanced) Cohorts	12 months	In this outcome measure, probability of participants being event-free at 12 months was reported, which was estimated by using a Kaplan-Meier method. (Here, event meant recurrent stroke or systemic embolism). Recurrent meant once participants were discharged from the hospital and became outpatients and then rehospitalized due to stroke or SE.
Time Course of Proportion of the Incidence of a Composite of Recurrent Stroke or Systemic Embolism (SE)-Free Participants at 18 Months: Secondary Prevention (Balanced) Cohorts	18 months	In this outcome measure, probability of participants being event-free at 18 months was reported, which was estimated by using a Kaplan-Meier method. (Here, event meant recurrent stroke or systemic embolism). Recurrent meant once participants were discharged from the hospital and became outpatients and then rehospitalized due to stroke or SE.
Time Course of Proportion of the Incidence of a Composite of Recurrent Stroke or Systemic Embolism (SE)-Free Participants at 24 Months: Secondary Prevention (Balanced) Cohorts	24 months	In this outcome measure, probability of participants being event-free at 24 months was reported, which was estimated by using a Kaplan-Meier method. (Here, event meant recurrent stroke or systemic embolism). Recurrent meant once participants were discharged from the hospital and became outpatients and then rehospitalized due to stroke or SE.

Secondary

Measure	Time frame	Description
Time Course of Proportion of Incidence of Recurrent Cardiogenic Cerebral Embolism-Free Participants: Secondary Prevention (Balanced) Cohorts	0 month, 6 months, 12 months, 18 months and 24 months	In this outcome measure, probability of participants being event-free at specified time points was reported, which was estimated by using a Kaplan-Meier method. (Here, event meant recurrent cardiogenic cerebral embolism). Recurrent meant once participants were discharged from the hospital and became outpatients and then rehospitalized due to cardiogenic cerebral embolism .
Number of Participants With Risk of Recurrent Cardiogenic Cerebral Embolism: Secondary Prevention (Balanced) Cohorts	0 month, 6 months, 12 months, 18 months and 24 months	In this outcome measure, number of participants with risk of recurrent cardiogenic cerebral embolism was reported. Recurrent meant once participants were discharged from the hospital and became outpatients and then rehospitalized due to cardiogenic cerebral embolism.
Incidence Rate of Recurrent Cerebral Infarction During the Follow-up Period: Secondary Prevention (Balanced) Cohorts	During Follow up period (Data collected between 2008 to 2021 [approximately 13 years])	Incidence rate was reported as events per 1,000 participant-years. First occurrence of recurrent cerebral infarction after index date during the follow-up period were considered. Recurrent meant once participants were discharged from the hospital and became outpatients and then rehospitalized due to cerebral infarction. Index date was defined as the next day of the day when participants diagnosed with NVAF initiated warfarin or apixaban. The follow up period was the period until the first observation of the earlier of the following from index date: until discontinuation of index OAC, switch of OAC, lack of records, occurrence of stroke, SE, or hemorrhagic events, or elapsing of 2 years from index date.
Time Course of Proportion of Incidence of Recurrent Cerebral Infarction-Free Participants: Secondary Prevention (Balanced) Cohorts	0 month, 6 months, 12 months, 18 months and 24 months	In this outcome measure, probability of participants being event-free at specified time points was reported, which was estimated by using a Kaplan-Meier method. (Here, event meant recurrent cerebral infarction). Recurrent meant once participants were discharged from the hospital and became outpatients and then rehospitalized due to cerebral infarction.
Number of Participants With Risk of Recurrent Cerebral Infarction: Secondary Prevention (Balanced) Cohorts	0 month, 6 months, 12 months, 18 months and 24 months	In this outcome measure, number of participants with risk of recurrent cerebral infarction was reported. Recurrent meant once participants were discharged from the hospital and became outpatients and then rehospitalized due to cerebral infarction.
Incidence Rate of Intracranial Hemorrhage During the Follow-up Period: Secondary Prevention (Balanced) Cohorts	During follow up period (Data collected between 2008 to 2021 [approximately 13 years])	Incidence rate was reported as events per 1,000 participant-years. First occurrence of intracranial hemorrhage after index date during the follow-up period were considered. Index date was defined as the next day of the day when participants diagnosed with NVAF initiated warfarin or apixaban. The follow up period was the period until the first observation of the earlier of the following from index date: until discontinuation of index OAC, switch of OAC, lack of records, occurrence of stroke, SE, or hemorrhagic events, or elapsing of 2 years from index date.
Time Course of Proportion of Incidence of Intracranial Hemorrhage-Free Participants: Secondary Prevention (Balanced) Cohorts	0 month, 6 months, 12 months, 18 months and 24 months	In this outcome measure, probability of participants being event-free at specified time points was reported, which was estimated by using a Kaplan-Meier method. (Here, event meant intracranial hemorrhage).
Number of Participants With Risk of Intracranial Hemorrhage: Secondary Prevention (Balanced) Cohorts	0 month, 6 months, 12 months, 18 months and 24 months	In this outcome measure, number of participants with risk of intracranial hemorrhage was reported.
Incidence Rate of Gastrointestinal Bleeding During the Follow-up Period: Secondary Prevention (Balanced) Cohorts	During follow up period (Data collected between 2008 to 2021 [approximately 13 years])	Incidence rate was reported as events per 1,000 participant-years. First occurrence of gastrointestinal bleeding after index date during the follow-up period were considered. Index date was defined as the next day of the day when participants diagnosed with NVAF initiated warfarin or apixaban. The follow up period was the period until the first observation of the earlier of the following from index date: until discontinuation of index OAC, switch of OAC, lack of records, occurrence of stroke, SE, or hemorrhagic events, or elapsing of 2 years from index date.
Time Course of Proportion of Incidence of Gastrointestinal Bleeding-Free Participants: Secondary Prevention (Balanced) Cohorts	0 month, 6 months, 12 months, 18 months and 24 months	In this outcome measure, probability of participants being event-free at specified time points was reported, which was estimated by using a Kaplan-Meier method. (Here, event meant gastrointestinal bleeding).
Number of Participants With Risk of Gastrointestinal Bleeding: Secondary Prevention (Balanced) Cohorts	0 month, 6 months, 12 months, 18 months and 24 months	In this outcome measure, number of participants with risk of gastrointestinal bleeding was reported.
Incidence Rate of Intraocular Bleeding During the Follow-up Period: Secondary Prevention (Balanced) Cohorts	During follow up period (Data collected between 2008 to 2021 [approximately 13 years])	Incidence rate was reported as events per 1,000 participant-years. First occurrence of intraocular bleeding after index date during the follow-up period were considered. Index date was defined as the next day of the day when participants diagnosed with NVAF initiated warfarin or apixaban. The follow up period was the period until the first observation of the earlier of the following from index date: until discontinuation of index OAC, switch of OAC, lack of records, occurrence of stroke, SE, or hemorrhagic events, or elapsing of 2 years from index date.
Time Course of Proportion of Incidence of Intraocular Bleeding-Free Participants: Secondary Prevention (Balanced) Cohorts	0 month, 6 months, 12 months, 18 months and 24 months	In this outcome measure, probability of participants being event-free at specified time points was reported, which was estimated by using a Kaplan-Meier method. (Here, event meant intraocular bleeding).
Number of Participants With Risk of Intraocular Bleeding: Secondary Prevention (Balanced) Cohorts	0 month, 6 months, 12 months, 18 months and 24 months	In this outcome measure, number of participants with risk of intraocular bleeding was reported.
Incidence Rate of Recurrent Cardiogenic Cerebral Embolism During the Follow-up Period: Secondary Prevention (Balanced) Cohorts	During follow up period (Data collected between 2008 to 2021 [approximately 13 years])	Incidence rate was reported as events per 1,000 participant-years. First occurrence of recurrent cardiogenic cerebral embolism after index date during the follow-up period were considered. Recurrent meant once participants were discharged from the hospital and became outpatients and then rehospitalized due to cardiogenic cerebral embolism. Index date was defined as the next day of the day when participants diagnosed with NVAF initiated warfarin or apixaban. The follow up period was the period until the first observation of the earlier of the following from index date: until discontinuation of index OAC, switch of OAC, lack of records, occurrence of stroke, SE, or hemorrhagic events, or elapsing of 2 years from index date.

Countries

Japan

Participant flow

Recruitment details

Data of participants diagnosed with non-valvular atrial fibrillation (NVAF) who were newly treated with warfarin or apixaban and were registered in Medical Data Vision (MDV) database during 2008 to 2021 (13 years) were included in this retrospective observational study.

Pre-assignment details

In this study, inverse probability of treatment weighted (IPTW) method was used in analysis of outcome measures to balance participant's characteristics between warfarin and apixaban cohorts (secondary prevention cohort). To avoid sample size inflation and to ensure appropriate estimation of variances, stabilized IPTW (s-IPTW) was used.

Participants by arm

Arm	Count
Primary Prevention Cohort: Apixaban Participants without prior diagnosis of stroke who were newly diagnosed with NVAF and initiated apixaban were included in this study cohort.	57,560
Primary Prevention Cohort: Warfarin Participants without prior diagnosis of stroke who were newly diagnosed with NVAF and initiated warfarin were included in this study cohort.	90,636
Secondary Prevention Cohort: Apixaban Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated apixaban were included in this study cohort.	18,216
Secondary Prevention Cohort: Warfarin Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated warfarin were included in this study cohort.	27,153
Total	193,565

Baseline characteristics

Characteristic	Total	Primary Prevention Cohort: Apixaban	Primary Prevention Cohort: Warfarin	Secondary Prevention Cohort: Apixaban	Secondary Prevention Cohort: Warfarin
Age, Customized 66 years to less than or equal to 75 years	57272 Participants	16219 Participants	28392 Participants	4557 Participants	8104 Participants
Age, Customized Greater than 75 years	108212 Participants	33565 Participants	46449 Participants	12279 Participants	15919 Participants
Age, Customized Less than or equal to 65 years	28081 Participants	7776 Participants	15795 Participants	1380 Participants	3130 Participants
Race and Ethnicity Not Collected	0 Participants	—	—	—	—
Sex: Female, Male Female	71382 Participants	22759 Participants	32232 Participants	6938 Participants	9453 Participants
Sex: Female, Male Male	122183 Participants	34801 Participants	58404 Participants	11278 Participants	17700 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 0	0 / 0
other Total, other adverse events	0 / 0	0 / 0
serious Total, serious adverse events	0 / 0	0 / 0

Outcome results

Primary

Incidence Rate of a Composite of Recurrent Stroke or Systemic Embolism (SE) During the Follow-up Period: Secondary Prevention (Balanced) Cohort

Incidence rate was reported as events per 1,000 participant-years. First occurrence of recurrent stroke or SE events after index date during the follow-up period were considered. Recurrent meant once participants were discharged from the hospital and became outpatients and then rehospitalized due to stroke or SE. Index date was defined as the next day of the day when participants diagnosed with NVAF initiated warfarin or apixaban. The follow up period was the period until the first observation of the earlier of the following from index date: until discontinuation of index oral anticoagulants (OAC), switch of OAC, lack of records, occurrence of stroke, SE, or hemorrhagic events, or elapsing of 2 years from index date.

Time frame: During follow up period (Data collected between 2008 to 2021 [approximately 13 years])

Population: Full analysis set included all eligible participants. Analysis was performed using sIPTW method to balance participant characteristics among reporting groups. sIPTW method created balanced virtual groups and hence overall number of participants analyzed is different from numbers in participant flow (not balanced).

Arm	Measure	Value (NUMBER)
Secondary Prevention Cohort (Balanced): Apixaban	Incidence Rate of a Composite of Recurrent Stroke or Systemic Embolism (SE) During the Follow-up Period: Secondary Prevention (Balanced) Cohort	41.217 Events Per 1000 Participant-Years
Secondary Prevention Cohort (Balanced): Warfarin	Incidence Rate of a Composite of Recurrent Stroke or Systemic Embolism (SE) During the Follow-up Period: Secondary Prevention (Balanced) Cohort	50.581 Events Per 1000 Participant-Years

Primary

Incidence Rate of Major Bleeding During the Follow-up Period: Secondary Prevention (Balanced) Cohorts

Incidence rate was reported as events per 1,000 participant-years. First occurrence of major bleeding after index date during the follow-up period was considered. Major bleeding, was defined as any bleeding which required hospitalization for treatment (the primary reason for the hospitalization was to treat the bleeding). Index date was defined as the next day of the day when participants diagnosed with NVAF initiated warfarin or apixaban. The follow up period was the period until the first observation of the earlier of the following from index date: until discontinuation of index OAC, switch of OAC, lack of records, occurrence of stroke, SE, or hemorrhagic events, or elapsing of 2 years from index date.

Time frame: During follow up period (Data collected between 2008 to 2021 [approximately 13 years])

Arm	Measure	Value (NUMBER)
Secondary Prevention Cohort (Balanced): Apixaban	Incidence Rate of Major Bleeding During the Follow-up Period: Secondary Prevention (Balanced) Cohorts	28.351 Events Per 1000 Participant-Years
Secondary Prevention Cohort (Balanced): Warfarin	Incidence Rate of Major Bleeding During the Follow-up Period: Secondary Prevention (Balanced) Cohorts	39.083 Events Per 1000 Participant-Years

Primary

Number of Participants With Risk of a Composite of Recurrent Stroke or SE at 0 Month: Secondary Prevention (Balanced) Cohorts

In this outcome measure, number of participants with risk of a composite of recurrent stroke (ischemic and hemorrhagic stroke)/SE at 0 month was reported. Recurrent meant once participants were discharged from the hospital and became outpatients and then rehospitalized due to stroke or SE.

Time frame: 0 month

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Secondary Prevention Cohort (Balanced): Apixaban	Number of Participants With Risk of a Composite of Recurrent Stroke or SE at 0 Month: Secondary Prevention (Balanced) Cohorts	7796 Participants
Secondary Prevention Cohort (Balanced): Warfarin	Number of Participants With Risk of a Composite of Recurrent Stroke or SE at 0 Month: Secondary Prevention (Balanced) Cohorts	11601 Participants

Primary

Number of Participants With Risk of a Composite of Recurrent Stroke or SE at 12 Months: Secondary Prevention (Balanced) Cohorts

In this outcome measure, number of participants with risk of a composite of recurrent stroke (ischemic and hemorrhagic stroke)/SE at 12 months was reported. Recurrent meant once participants were discharged from the hospital and became outpatients and then rehospitalized due to stroke or SE.

Time frame: 12 months

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Secondary Prevention Cohort (Balanced): Apixaban	Number of Participants With Risk of a Composite of Recurrent Stroke or SE at 12 Months: Secondary Prevention (Balanced) Cohorts	1426 Participants
Secondary Prevention Cohort (Balanced): Warfarin	Number of Participants With Risk of a Composite of Recurrent Stroke or SE at 12 Months: Secondary Prevention (Balanced) Cohorts	1670 Participants

Primary

Number of Participants With Risk of a Composite of Recurrent Stroke or SE at 18 Months: Secondary Prevention (Balanced) Cohorts

In this outcome measure, number of participants with risk of a composite of recurrent stroke (ischemic and hemorrhagic stroke)/SE at 18 months was reported. Recurrent meant once participants were discharged from the hospital and became outpatients and then rehospitalized due to stroke or SE.

Time frame: 18 months

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Secondary Prevention Cohort (Balanced): Apixaban	Number of Participants With Risk of a Composite of Recurrent Stroke or SE at 18 Months: Secondary Prevention (Balanced) Cohorts	1095 Participants
Secondary Prevention Cohort (Balanced): Warfarin	Number of Participants With Risk of a Composite of Recurrent Stroke or SE at 18 Months: Secondary Prevention (Balanced) Cohorts	1272 Participants

Primary

Number of Participants With Risk of a Composite of Recurrent Stroke or SE at 24 Months: Secondary Prevention (Balanced) Cohorts

In this outcome measure, number of participants with risk of a composite of recurrent stroke (ischemic and hemorrhagic stroke)/SE at 24 months was reported. Recurrent meant once participants were discharged from the hospital and became outpatients and then rehospitalized due to stroke or SE.

Time frame: 24 months

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Secondary Prevention Cohort (Balanced): Apixaban	Number of Participants With Risk of a Composite of Recurrent Stroke or SE at 24 Months: Secondary Prevention (Balanced) Cohorts	845 Participants
Secondary Prevention Cohort (Balanced): Warfarin	Number of Participants With Risk of a Composite of Recurrent Stroke or SE at 24 Months: Secondary Prevention (Balanced) Cohorts	1024 Participants

Comparison: Statistical analysis has been presented for all time points from 0 to 24 months.p-value: 0.01395% CI: [0.69, 0.957]t-test, 2 sided

Primary

Number of Participants With Risk of a Composite of Recurrent Stroke or SE at 6 Months: Secondary Prevention (Balanced) Cohorts

In this outcome measure, number of participants with risk of a composite of recurrent stroke (ischemic and hemorrhagic stroke)/SE at 6 months was reported. Recurrent meant once participants were discharged from the hospital and became outpatients and then rehospitalized due to stroke or SE.

Time frame: 6 months

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Secondary Prevention Cohort (Balanced): Apixaban	Number of Participants With Risk of a Composite of Recurrent Stroke or SE at 6 Months: Secondary Prevention (Balanced) Cohorts	2061 Participants
Secondary Prevention Cohort (Balanced): Warfarin	Number of Participants With Risk of a Composite of Recurrent Stroke or SE at 6 Months: Secondary Prevention (Balanced) Cohorts	2393 Participants

Primary

Number of Participants With Risk of Major Bleeding at 0 Month: Secondary Prevention (Balanced) Cohorts

In this outcome measure, number of participants with risk of major bleeding at 0 month was reported. Major bleeding, was defined as any bleeding which required hospitalization for treatment (the primary reason for the hospitalization was to treat the bleeding).

Time frame: 0 month

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Secondary Prevention Cohort (Balanced): Apixaban	Number of Participants With Risk of Major Bleeding at 0 Month: Secondary Prevention (Balanced) Cohorts	7796 Participants
Secondary Prevention Cohort (Balanced): Warfarin	Number of Participants With Risk of Major Bleeding at 0 Month: Secondary Prevention (Balanced) Cohorts	11601 Participants

Primary

Number of Participants With Risk of Major Bleeding at 12 Months: Secondary Prevention (Balanced) Cohorts

In this outcome measure, number of participants with risk of major bleeding at 12 months was reported. Major bleeding, was defined as any bleeding which required hospitalization for treatment (the primary reason for the hospitalization was to treat the bleeding).

Time frame: 12 months

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Secondary Prevention Cohort (Balanced): Apixaban	Number of Participants With Risk of Major Bleeding at 12 Months: Secondary Prevention (Balanced) Cohorts	1448 Participants
Secondary Prevention Cohort (Balanced): Warfarin	Number of Participants With Risk of Major Bleeding at 12 Months: Secondary Prevention (Balanced) Cohorts	1685 Participants

Primary

Number of Participants With Risk of Major Bleeding at 18 Months: Secondary Prevention (Balanced) Cohorts

In this outcome measure, number of participants with risk of major bleeding at 18 months was reported. Major bleeding, was defined as any bleeding which required hospitalization for treatment (the primary reason for the hospitalization was to treat the bleeding).

Time frame: 18 months

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Secondary Prevention Cohort (Balanced): Apixaban	Number of Participants With Risk of Major Bleeding at 18 Months: Secondary Prevention (Balanced) Cohorts	1110 Participants
Secondary Prevention Cohort (Balanced): Warfarin	Number of Participants With Risk of Major Bleeding at 18 Months: Secondary Prevention (Balanced) Cohorts	1283 Participants

Primary

Number of Participants With Risk of Major Bleeding at 24 Months: Secondary Prevention (Balanced) Cohorts

In this outcome measure, number of participants with risk of major bleeding at 24 months was reported. Major bleeding, was defined as any bleeding which required hospitalization for treatment (the primary reason for the hospitalization was to treat the bleeding).

Time frame: 24 months

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Secondary Prevention Cohort (Balanced): Apixaban	Number of Participants With Risk of Major Bleeding at 24 Months: Secondary Prevention (Balanced) Cohorts	850 Participants
Secondary Prevention Cohort (Balanced): Warfarin	Number of Participants With Risk of Major Bleeding at 24 Months: Secondary Prevention (Balanced) Cohorts	1028 Participants

Comparison: Statistical analysis has been presented for all time points from 0 to 24 months.p-value: 0.00195% CI: [0.599, 0.881]t-test, 2 sided

Primary

Number of Participants With Risk of Major Bleeding at 6 Months: Secondary Prevention (Balanced) Cohorts

In this outcome measure, number of participants with risk of major bleeding at 6 months was reported. Major bleeding, was defined as any bleeding which required hospitalization for treatment (the primary reason for the hospitalization was to treat the bleeding).

Time frame: 6 months

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Secondary Prevention Cohort (Balanced): Apixaban	Number of Participants With Risk of Major Bleeding at 6 Months: Secondary Prevention (Balanced) Cohorts	2081 Participants
Secondary Prevention Cohort (Balanced): Warfarin	Number of Participants With Risk of Major Bleeding at 6 Months: Secondary Prevention (Balanced) Cohorts	2412 Participants

Primary

Time Course of Proportion of Incidence of Major Bleeding-Free Participants at 0 Month: Secondary Prevention (Balanced) Cohorts

In this outcome measure, probability of participants being event-free at 0 month was reported, which was estimated by using a Kaplan-Meier method. (Here, event meant major bleeding). Major bleeding, was defined as any bleeding which required hospitalization for treatment (the primary reason for the hospitalization was to treat the bleeding).

Time frame: 0 month

Arm	Measure	Value (NUMBER)
Secondary Prevention Cohort (Balanced): Apixaban	Time Course of Proportion of Incidence of Major Bleeding-Free Participants at 0 Month: Secondary Prevention (Balanced) Cohorts	1.000 Probability of being event free
Secondary Prevention Cohort (Balanced): Warfarin	Time Course of Proportion of Incidence of Major Bleeding-Free Participants at 0 Month: Secondary Prevention (Balanced) Cohorts	1.000 Probability of being event free

Primary

Time Course of Proportion of Incidence of Major Bleeding-Free Participants at 12 Months: Secondary Prevention (Balanced) Cohorts

In this outcome measure, probability of participants being event-free at 12 months was reported, which was estimated by using a Kaplan-Meier method. (Here, event meant major bleeding). Major bleeding, was defined as any bleeding which required hospitalization for treatment (the primary reason for the hospitalization was to treat the bleeding).

Time frame: 12 months

Arm	Measure	Value (NUMBER)
Secondary Prevention Cohort (Balanced): Apixaban	Time Course of Proportion of Incidence of Major Bleeding-Free Participants at 12 Months: Secondary Prevention (Balanced) Cohorts	0.968 Probability of being event free
Secondary Prevention Cohort (Balanced): Warfarin	Time Course of Proportion of Incidence of Major Bleeding-Free Participants at 12 Months: Secondary Prevention (Balanced) Cohorts	0.963 Probability of being event free

Primary

Time Course of Proportion of Incidence of Major Bleeding-Free Participants at 18 Months: Secondary Prevention (Balanced) Cohorts

In this outcome measure, probability of participants being event-free at 18 months was reported, which was estimated by using a Kaplan-Meier method. (Here, event meant major bleeding). Major bleeding, was defined as any bleeding which required hospitalization for treatment (the primary reason for the hospitalization was to treat the bleeding).

Time frame: 18 months

Arm	Measure	Value (NUMBER)
Secondary Prevention Cohort (Balanced): Apixaban	Time Course of Proportion of Incidence of Major Bleeding-Free Participants at 18 Months: Secondary Prevention (Balanced) Cohorts	0.958 Probability of being event free
Secondary Prevention Cohort (Balanced): Warfarin	Time Course of Proportion of Incidence of Major Bleeding-Free Participants at 18 Months: Secondary Prevention (Balanced) Cohorts	0.949 Probability of being event free

Primary

Time Course of Proportion of Incidence of Major Bleeding-Free Participants at 24 Months: Secondary Prevention (Balanced) Cohorts

In this outcome measure, probability of participants being event-free at 24 months was reported, which was estimated by using a Kaplan-Meier method. (Here, event meant major bleeding). Major bleeding, was defined as any bleeding which required hospitalization for treatment (the primary reason for the hospitalization was to treat the bleeding).

Time frame: 24 months

Arm	Measure	Value (NUMBER)
Secondary Prevention Cohort (Balanced): Apixaban	Time Course of Proportion of Incidence of Major Bleeding-Free Participants at 24 Months: Secondary Prevention (Balanced) Cohorts	0.948 Probability of being event free
Secondary Prevention Cohort (Balanced): Warfarin	Time Course of Proportion of Incidence of Major Bleeding-Free Participants at 24 Months: Secondary Prevention (Balanced) Cohorts	0.932 Probability of being event free

Comparison: Statistical analysis has been presented for all time points from 0 to 24 months.p-value: 0.002Log Rank

Primary

Time Course of Proportion of Incidence of Major Bleeding-Free Participants at 6 Months: Secondary Prevention (Balanced) Cohorts

In this outcome measure, probability of participants being event-free at 6 months was reported, which was estimated by using a Kaplan-Meier method. (Here, event meant major bleeding). Major bleeding, was defined as any bleeding which required hospitalization for treatment (the primary reason for the hospitalization was to treat the bleeding).

Time frame: 6 months

Arm	Measure	Value (NUMBER)
Secondary Prevention Cohort (Balanced): Apixaban	Time Course of Proportion of Incidence of Major Bleeding-Free Participants at 6 Months: Secondary Prevention (Balanced) Cohorts	0.983 Probability of being event free
Secondary Prevention Cohort (Balanced): Warfarin	Time Course of Proportion of Incidence of Major Bleeding-Free Participants at 6 Months: Secondary Prevention (Balanced) Cohorts	0.976 Probability of being event free

Primary

Time Course of Proportion of the Incidence of a Composite of Recurrent Stroke or Systemic Embolism (SE)-Free Participants at 0 Month: Secondary Prevention (Balanced) Cohorts

In this outcome measure, probability of participants being event-free at 0 month was reported, which was estimated by using a Kaplan-Meier method. (Here, event meant recurrent stroke or systemic embolism). Recurrent meant once participants were discharged from the hospital and became outpatients and then rehospitalized due to stroke or SE.

Time frame: 0 month

Arm	Measure	Value (NUMBER)
Secondary Prevention Cohort (Balanced): Apixaban	Time Course of Proportion of the Incidence of a Composite of Recurrent Stroke or Systemic Embolism (SE)-Free Participants at 0 Month: Secondary Prevention (Balanced) Cohorts	1.000 Probability of being event free
Secondary Prevention Cohort (Balanced): Warfarin	Time Course of Proportion of the Incidence of a Composite of Recurrent Stroke or Systemic Embolism (SE)-Free Participants at 0 Month: Secondary Prevention (Balanced) Cohorts	1.000 Probability of being event free

Primary

Time Course of Proportion of the Incidence of a Composite of Recurrent Stroke or Systemic Embolism (SE)-Free Participants at 12 Months: Secondary Prevention (Balanced) Cohorts

In this outcome measure, probability of participants being event-free at 12 months was reported, which was estimated by using a Kaplan-Meier method. (Here, event meant recurrent stroke or systemic embolism). Recurrent meant once participants were discharged from the hospital and became outpatients and then rehospitalized due to stroke or SE.

Time frame: 12 months

Arm	Measure	Value (NUMBER)
Secondary Prevention Cohort (Balanced): Apixaban	Time Course of Proportion of the Incidence of a Composite of Recurrent Stroke or Systemic Embolism (SE)-Free Participants at 12 Months: Secondary Prevention (Balanced) Cohorts	0.953 Probability of being event free
Secondary Prevention Cohort (Balanced): Warfarin	Time Course of Proportion of the Incidence of a Composite of Recurrent Stroke or Systemic Embolism (SE)-Free Participants at 12 Months: Secondary Prevention (Balanced) Cohorts	0.948 Probability of being event free

Primary

Time Course of Proportion of the Incidence of a Composite of Recurrent Stroke or Systemic Embolism (SE)-Free Participants at 18 Months: Secondary Prevention (Balanced) Cohorts

In this outcome measure, probability of participants being event-free at 18 months was reported, which was estimated by using a Kaplan-Meier method. (Here, event meant recurrent stroke or systemic embolism). Recurrent meant once participants were discharged from the hospital and became outpatients and then rehospitalized due to stroke or SE.

Time frame: 18 months

Arm	Measure	Value (NUMBER)
Secondary Prevention Cohort (Balanced): Apixaban	Time Course of Proportion of the Incidence of a Composite of Recurrent Stroke or Systemic Embolism (SE)-Free Participants at 18 Months: Secondary Prevention (Balanced) Cohorts	0.942 Probability of being event free
Secondary Prevention Cohort (Balanced): Warfarin	Time Course of Proportion of the Incidence of a Composite of Recurrent Stroke or Systemic Embolism (SE)-Free Participants at 18 Months: Secondary Prevention (Balanced) Cohorts	0.932 Probability of being event free

Primary

Time Course of Proportion of the Incidence of a Composite of Recurrent Stroke or Systemic Embolism (SE)-Free Participants at 24 Months: Secondary Prevention (Balanced) Cohorts

In this outcome measure, probability of participants being event-free at 24 months was reported, which was estimated by using a Kaplan-Meier method. (Here, event meant recurrent stroke or systemic embolism). Recurrent meant once participants were discharged from the hospital and became outpatients and then rehospitalized due to stroke or SE.

Time frame: 24 months

Arm	Measure	Value (NUMBER)
Secondary Prevention Cohort (Balanced): Apixaban	Time Course of Proportion of the Incidence of a Composite of Recurrent Stroke or Systemic Embolism (SE)-Free Participants at 24 Months: Secondary Prevention (Balanced) Cohorts	0.933 Probability of being event free
Secondary Prevention Cohort (Balanced): Warfarin	Time Course of Proportion of the Incidence of a Composite of Recurrent Stroke or Systemic Embolism (SE)-Free Participants at 24 Months: Secondary Prevention (Balanced) Cohorts	0.915 Probability of being event free

Comparison: Statistical analysis has been presented for all time points from 0 to 24 months.p-value: 0.016Log Rank

Primary

Time Course of Proportion of the Incidence of a Composite of Recurrent Stroke or Systemic Embolism (SE)-Free Participants at 6 Months: Secondary Prevention (Balanced) Cohorts

In this outcome measure, probability of participants being event-free at 6 months was reported, which was estimated by using a Kaplan-Meier method. (Here, event meant recurrent stroke or systemic embolism). Recurrent meant once participants were discharged from the hospital and became outpatients and then rehospitalized due to stroke or SE.

Time frame: 6 months

Arm	Measure	Value (NUMBER)
Secondary Prevention Cohort (Balanced): Apixaban	Time Course of Proportion of the Incidence of a Composite of Recurrent Stroke or Systemic Embolism (SE)-Free Participants at 6 Months: Secondary Prevention (Balanced) Cohorts	0.971 Probability of being event free
Secondary Prevention Cohort (Balanced): Warfarin	Time Course of Proportion of the Incidence of a Composite of Recurrent Stroke or Systemic Embolism (SE)-Free Participants at 6 Months: Secondary Prevention (Balanced) Cohorts	0.967 Probability of being event free

Secondary

Incidence Rate of Gastrointestinal Bleeding During the Follow-up Period: Secondary Prevention (Balanced) Cohorts

Incidence rate was reported as events per 1,000 participant-years. First occurrence of gastrointestinal bleeding after index date during the follow-up period were considered. Index date was defined as the next day of the day when participants diagnosed with NVAF initiated warfarin or apixaban. The follow up period was the period until the first observation of the earlier of the following from index date: until discontinuation of index OAC, switch of OAC, lack of records, occurrence of stroke, SE, or hemorrhagic events, or elapsing of 2 years from index date.

Time frame: During follow up period (Data collected between 2008 to 2021 [approximately 13 years])

Arm	Measure	Value (NUMBER)
Secondary Prevention Cohort (Balanced): Apixaban	Incidence Rate of Gastrointestinal Bleeding During the Follow-up Period: Secondary Prevention (Balanced) Cohorts	47.634 Events Per 1000 Participant-Years
Secondary Prevention Cohort (Balanced): Warfarin	Incidence Rate of Gastrointestinal Bleeding During the Follow-up Period: Secondary Prevention (Balanced) Cohorts	47.876 Events Per 1000 Participant-Years

Secondary

Incidence Rate of Intracranial Hemorrhage During the Follow-up Period: Secondary Prevention (Balanced) Cohorts

Incidence rate was reported as events per 1,000 participant-years. First occurrence of intracranial hemorrhage after index date during the follow-up period were considered. Index date was defined as the next day of the day when participants diagnosed with NVAF initiated warfarin or apixaban. The follow up period was the period until the first observation of the earlier of the following from index date: until discontinuation of index OAC, switch of OAC, lack of records, occurrence of stroke, SE, or hemorrhagic events, or elapsing of 2 years from index date.

Time frame: During follow up period (Data collected between 2008 to 2021 [approximately 13 years])

Arm	Measure	Value (NUMBER)
Secondary Prevention Cohort (Balanced): Apixaban	Incidence Rate of Intracranial Hemorrhage During the Follow-up Period: Secondary Prevention (Balanced) Cohorts	38.214 Events Per 1000 Participant-Years
Secondary Prevention Cohort (Balanced): Warfarin	Incidence Rate of Intracranial Hemorrhage During the Follow-up Period: Secondary Prevention (Balanced) Cohorts	44.868 Events Per 1000 Participant-Years

Secondary

Incidence Rate of Intraocular Bleeding During the Follow-up Period: Secondary Prevention (Balanced) Cohorts

Incidence rate was reported as events per 1,000 participant-years. First occurrence of intraocular bleeding after index date during the follow-up period were considered. Index date was defined as the next day of the day when participants diagnosed with NVAF initiated warfarin or apixaban. The follow up period was the period until the first observation of the earlier of the following from index date: until discontinuation of index OAC, switch of OAC, lack of records, occurrence of stroke, SE, or hemorrhagic events, or elapsing of 2 years from index date.

Time frame: During follow up period (Data collected between 2008 to 2021 [approximately 13 years])

Arm	Measure	Value (NUMBER)
Secondary Prevention Cohort (Balanced): Apixaban	Incidence Rate of Intraocular Bleeding During the Follow-up Period: Secondary Prevention (Balanced) Cohorts	3.748 Events Per 1000 Participant-Years
Secondary Prevention Cohort (Balanced): Warfarin	Incidence Rate of Intraocular Bleeding During the Follow-up Period: Secondary Prevention (Balanced) Cohorts	8.627 Events Per 1000 Participant-Years

Secondary

Incidence Rate of Recurrent Cardiogenic Cerebral Embolism During the Follow-up Period: Secondary Prevention (Balanced) Cohorts

Incidence rate was reported as events per 1,000 participant-years. First occurrence of recurrent cardiogenic cerebral embolism after index date during the follow-up period were considered. Recurrent meant once participants were discharged from the hospital and became outpatients and then rehospitalized due to cardiogenic cerebral embolism. Index date was defined as the next day of the day when participants diagnosed with NVAF initiated warfarin or apixaban. The follow up period was the period until the first observation of the earlier of the following from index date: until discontinuation of index OAC, switch of OAC, lack of records, occurrence of stroke, SE, or hemorrhagic events, or elapsing of 2 years from index date.

Time frame: During follow up period (Data collected between 2008 to 2021 [approximately 13 years])

Arm	Measure	Value (NUMBER)
Secondary Prevention Cohort (Balanced): Apixaban	Incidence Rate of Recurrent Cardiogenic Cerebral Embolism During the Follow-up Period: Secondary Prevention (Balanced) Cohorts	10.355 Events Per 1000 Participant-Years
Secondary Prevention Cohort (Balanced): Warfarin	Incidence Rate of Recurrent Cardiogenic Cerebral Embolism During the Follow-up Period: Secondary Prevention (Balanced) Cohorts	17.893 Events Per 1000 Participant-Years

Secondary

Incidence Rate of Recurrent Cerebral Infarction During the Follow-up Period: Secondary Prevention (Balanced) Cohorts

Incidence rate was reported as events per 1,000 participant-years. First occurrence of recurrent cerebral infarction after index date during the follow-up period were considered. Recurrent meant once participants were discharged from the hospital and became outpatients and then rehospitalized due to cerebral infarction. Index date was defined as the next day of the day when participants diagnosed with NVAF initiated warfarin or apixaban. The follow up period was the period until the first observation of the earlier of the following from index date: until discontinuation of index OAC, switch of OAC, lack of records, occurrence of stroke, SE, or hemorrhagic events, or elapsing of 2 years from index date.

Time frame: During Follow up period (Data collected between 2008 to 2021 [approximately 13 years])

Arm	Measure	Value (NUMBER)
Secondary Prevention Cohort (Balanced): Apixaban	Incidence Rate of Recurrent Cerebral Infarction During the Follow-up Period: Secondary Prevention (Balanced) Cohorts	15.481 Events Per 1000 Participant-Years
Secondary Prevention Cohort (Balanced): Warfarin	Incidence Rate of Recurrent Cerebral Infarction During the Follow-up Period: Secondary Prevention (Balanced) Cohorts	13.430 Events Per 1000 Participant-Years

Secondary

Number of Participants With Risk of Gastrointestinal Bleeding: Secondary Prevention (Balanced) Cohorts

In this outcome measure, number of participants with risk of gastrointestinal bleeding was reported.