Trial Outcomes & Findings for Safety and Effectiveness of Apixaban Compared to Warfarin in Secondary Prevention in Patients With Atrial Fibrillation (NCT NCT05321810)

Results Overview

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.

Recruitment status

COMPLETED

Target enrollment

193565 participants

Primary outcome timeframe

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

Results posted on

2024-01-11

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	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.	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.	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.	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.
Overall Study STARTED	57560	90636	18216	27153
Overall Study COMPLETED	57560	90636	18216	27153
Overall Study NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Primary Prevention Cohort: Apixaban n=57560 Participants Participants without prior diagnosis of stroke who were newly diagnosed with NVAF and initiated apixaban were included in this study cohort.	Primary Prevention Cohort: Warfarin n=90636 Participants Participants without prior diagnosis of stroke who were newly diagnosed with NVAF and initiated warfarin were included in this study cohort.	Secondary Prevention Cohort: Apixaban n=18216 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated apixaban were included in this study cohort.	Secondary Prevention Cohort: Warfarin n=27153 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated warfarin were included in this study cohort.	Total n=193565 Participants Total of all reporting groups
Age, Customized Less than or equal to 65 years	7776 Participants n=57560 Participants	15795 Participants n=90636 Participants	1380 Participants n=18216 Participants	3130 Participants n=27153 Participants	28081 Participants n=193565 Participants
Age, Customized 66 years to less than or equal to 75 years	16219 Participants n=57560 Participants	28392 Participants n=90636 Participants	4557 Participants n=18216 Participants	8104 Participants n=27153 Participants	57272 Participants n=193565 Participants
Age, Customized Greater than 75 years	33565 Participants n=57560 Participants	46449 Participants n=90636 Participants	12279 Participants n=18216 Participants	15919 Participants n=27153 Participants	108212 Participants n=193565 Participants
Sex: Female, Male Female	22759 Participants n=57560 Participants	32232 Participants n=90636 Participants	6938 Participants n=18216 Participants	9453 Participants n=27153 Participants	71382 Participants n=193565 Participants
Sex: Female, Male Male	34801 Participants n=57560 Participants	58404 Participants n=90636 Participants	11278 Participants n=18216 Participants	17700 Participants n=27153 Participants	122183 Participants n=193565 Participants
Race and Ethnicity Not Collected	—	—	—	—	0 Participants Race and Ethnicity were not collected from any participant.

PRIMARY outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure	Secondary Prevention Cohort (Balanced): Apixaban n=7796 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated apixaban on the index date and were balanced using sIPTW method.	Secondary Prevention Cohort (Balanced): Warfarin n=11601 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated warfarin on the index date and were balanced using sIPTW method.
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 Interval 36.274 to 46.834	50.581 Events Per 1000 Participant-Years Interval 45.658 to 56.034

PRIMARY outcome

Timeframe: 0 month

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).

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".

Outcome measures

Outcome measures
Measure	Secondary Prevention Cohort (Balanced): Apixaban n=7796 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated apixaban on the index date and were balanced using sIPTW method.	Secondary Prevention Cohort (Balanced): Warfarin n=11601 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated warfarin on the index date and were balanced using sIPTW method.
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 Interval 1.0 to 1.0	1.000 Probability of being event free Interval 1.0 to 1.0

PRIMARY outcome

Timeframe: 6 months

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).

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".

Outcome measures

Outcome measures
Measure	Secondary Prevention Cohort (Balanced): Apixaban n=7796 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated apixaban on the index date and were balanced using sIPTW method.	Secondary Prevention Cohort (Balanced): Warfarin n=11601 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated warfarin on the index date and were balanced using sIPTW method.
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 Interval 0.966 to 0.976	0.967 Probability of being event free Interval 0.961 to 0.972

PRIMARY outcome

Timeframe: 12 months

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).

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".

Outcome measures

Outcome measures
Measure	Secondary Prevention Cohort (Balanced): Apixaban n=7796 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated apixaban on the index date and were balanced using sIPTW method.	Secondary Prevention Cohort (Balanced): Warfarin n=11601 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated warfarin on the index date and were balanced using sIPTW method.
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 Interval 0.946 to 0.96	0.948 Probability of being event free Interval 0.938 to 0.956

PRIMARY outcome

Timeframe: 18 months

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).

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".

Outcome measures

Outcome measures
Measure	Secondary Prevention Cohort (Balanced): Apixaban n=7796 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated apixaban on the index date and were balanced using sIPTW method.	Secondary Prevention Cohort (Balanced): Warfarin n=11601 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated warfarin on the index date and were balanced using sIPTW method.
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 Interval 0.933 to 0.951	0.932 Probability of being event free Interval 0.92 to 0.943

PRIMARY outcome

Timeframe: 24 months

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).

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".

Outcome measures

Outcome measures
Measure	Secondary Prevention Cohort (Balanced): Apixaban n=7796 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated apixaban on the index date and were balanced using sIPTW method.	Secondary Prevention Cohort (Balanced): Warfarin n=11601 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated warfarin on the index date and were balanced using sIPTW method.
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 Interval 0.921 to 0.942	0.915 Probability of being event free Interval 0.9 to 0.928

PRIMARY outcome

Timeframe: 0 month

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).

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".

Outcome measures

Outcome measures
Measure	Secondary Prevention Cohort (Balanced): Apixaban n=7796 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated apixaban on the index date and were balanced using sIPTW method.	Secondary Prevention Cohort (Balanced): Warfarin n=11601 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated warfarin on the index date and were balanced using sIPTW method.
Number of Participants With Risk of a Composite of Recurrent Stroke or SE at 0 Month: Secondary Prevention (Balanced) Cohorts	7796 Participants	11601 Participants

PRIMARY outcome

Timeframe: 6 months

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).

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".

Outcome measures

Outcome measures
Measure	Secondary Prevention Cohort (Balanced): Apixaban n=7796 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated apixaban on the index date and were balanced using sIPTW method.	Secondary Prevention Cohort (Balanced): Warfarin n=11601 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated warfarin on the index date and were balanced using sIPTW method.
Number of Participants With Risk of a Composite of Recurrent Stroke or SE at 6 Months: Secondary Prevention (Balanced) Cohorts	2061 Participants	2393 Participants

PRIMARY outcome

Timeframe: 12 months

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).

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".

Outcome measures

Outcome measures
Measure	Secondary Prevention Cohort (Balanced): Apixaban n=7796 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated apixaban on the index date and were balanced using sIPTW method.	Secondary Prevention Cohort (Balanced): Warfarin n=11601 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated warfarin on the index date and were balanced using sIPTW method.
Number of Participants With Risk of a Composite of Recurrent Stroke or SE at 12 Months: Secondary Prevention (Balanced) Cohorts	1426 Participants	1670 Participants

PRIMARY outcome

Timeframe: 18 months

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).

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".

Outcome measures

Outcome measures
Measure	Secondary Prevention Cohort (Balanced): Apixaban n=7796 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated apixaban on the index date and were balanced using sIPTW method.	Secondary Prevention Cohort (Balanced): Warfarin n=11601 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated warfarin on the index date and were balanced using sIPTW method.
Number of Participants With Risk of a Composite of Recurrent Stroke or SE at 18 Months: Secondary Prevention (Balanced) Cohorts	1095 Participants	1272 Participants

PRIMARY outcome

Timeframe: 24 months

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).

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".

Outcome measures

Outcome measures
Measure	Secondary Prevention Cohort (Balanced): Apixaban n=7796 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated apixaban on the index date and were balanced using sIPTW method.	Secondary Prevention Cohort (Balanced): Warfarin n=11601 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated warfarin on the index date and were balanced using sIPTW method.
Number of Participants With Risk of a Composite of Recurrent Stroke or SE at 24 Months: Secondary Prevention (Balanced) Cohorts	845 Participants	1024 Participants

PRIMARY outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure	Secondary Prevention Cohort (Balanced): Apixaban n=7796 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated apixaban on the index date and were balanced using sIPTW method.	Secondary Prevention Cohort (Balanced): Warfarin n=11601 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated warfarin on the index date and were balanced using sIPTW method.
Incidence Rate of Major Bleeding During the Follow-up Period: Secondary Prevention (Balanced) Cohorts	28.351 Events Per 1000 Participant-Years Interval 24.318 to 33.054	39.083 Events Per 1000 Participant-Years Interval 34.793 to 43.903

PRIMARY outcome

Timeframe: 0 month

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).

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).

Outcome measures

Outcome measures
Measure	Secondary Prevention Cohort (Balanced): Apixaban n=7796 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated apixaban on the index date and were balanced using sIPTW method.	Secondary Prevention Cohort (Balanced): Warfarin n=11601 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated warfarin on the index date and were balanced using sIPTW method.
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 Interval 1.0 to 1.0	1.000 Probability of being event free Interval 1.0 to 1.0

PRIMARY outcome

Timeframe: 6 months

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).

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).

Outcome measures

Outcome measures
Measure	Secondary Prevention Cohort (Balanced): Apixaban n=7796 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated apixaban on the index date and were balanced using sIPTW method.	Secondary Prevention Cohort (Balanced): Warfarin n=11601 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated warfarin on the index date and were balanced using sIPTW method.
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 Interval 0.979 to 0.986	0.976 Probability of being event free Interval 0.97 to 0.98

PRIMARY outcome

Timeframe: 12 months

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).

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).

Outcome measures

Outcome measures
Measure	Secondary Prevention Cohort (Balanced): Apixaban n=7796 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated apixaban on the index date and were balanced using sIPTW method.	Secondary Prevention Cohort (Balanced): Warfarin n=11601 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated warfarin on the index date and were balanced using sIPTW method.
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 Interval 0.961 to 0.974	0.963 Probability of being event free Interval 0.955 to 0.97

PRIMARY outcome

Timeframe: 18 months

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).

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).

Outcome measures

Outcome measures
Measure	Secondary Prevention Cohort (Balanced): Apixaban n=7796 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated apixaban on the index date and were balanced using sIPTW method.	Secondary Prevention Cohort (Balanced): Warfarin n=11601 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated warfarin on the index date and were balanced using sIPTW method.
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 Interval 0.95 to 0.966	0.949 Probability of being event free Interval 0.938 to 0.958

PRIMARY outcome

Timeframe: 24 months

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).

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).

Outcome measures

Outcome measures
Measure	Secondary Prevention Cohort (Balanced): Apixaban n=7796 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated apixaban on the index date and were balanced using sIPTW method.	Secondary Prevention Cohort (Balanced): Warfarin n=11601 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated warfarin on the index date and were balanced using sIPTW method.
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 Interval 0.937 to 0.957	0.932 Probability of being event free Interval 0.918 to 0.944

PRIMARY outcome

Timeframe: 0 month

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).

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).

Outcome measures

Outcome measures
Measure	Secondary Prevention Cohort (Balanced): Apixaban n=7796 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated apixaban on the index date and were balanced using sIPTW method.	Secondary Prevention Cohort (Balanced): Warfarin n=11601 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated warfarin on the index date and were balanced using sIPTW method.
Number of Participants With Risk of Major Bleeding at 0 Month: Secondary Prevention (Balanced) Cohorts	7796 Participants	11601 Participants

PRIMARY outcome

Timeframe: 6 months

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).

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).

Outcome measures

Outcome measures
Measure	Secondary Prevention Cohort (Balanced): Apixaban n=7796 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated apixaban on the index date and were balanced using sIPTW method.	Secondary Prevention Cohort (Balanced): Warfarin n=11601 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated warfarin on the index date and were balanced using sIPTW method.
Number of Participants With Risk of Major Bleeding at 6 Months: Secondary Prevention (Balanced) Cohorts	2081 Participants	2412 Participants

PRIMARY outcome

Timeframe: 12 months

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).

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).

Outcome measures

Outcome measures
Measure	Secondary Prevention Cohort (Balanced): Apixaban n=7796 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated apixaban on the index date and were balanced using sIPTW method.	Secondary Prevention Cohort (Balanced): Warfarin n=11601 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated warfarin on the index date and were balanced using sIPTW method.
Number of Participants With Risk of Major Bleeding at 12 Months: Secondary Prevention (Balanced) Cohorts	1448 Participants	1685 Participants

PRIMARY outcome

Timeframe: 18 months

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).

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).

Outcome measures

Outcome measures
Measure	Secondary Prevention Cohort (Balanced): Apixaban n=7796 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated apixaban on the index date and were balanced using sIPTW method.	Secondary Prevention Cohort (Balanced): Warfarin n=11601 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated warfarin on the index date and were balanced using sIPTW method.
Number of Participants With Risk of Major Bleeding at 18 Months: Secondary Prevention (Balanced) Cohorts	1110 Participants	1283 Participants

PRIMARY outcome

Timeframe: 24 months

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).

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).

Outcome measures

Outcome measures
Measure	Secondary Prevention Cohort (Balanced): Apixaban n=7796 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated apixaban on the index date and were balanced using sIPTW method.	Secondary Prevention Cohort (Balanced): Warfarin n=11601 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated warfarin on the index date and were balanced using sIPTW method.
Number of Participants With Risk of Major Bleeding at 24 Months: Secondary Prevention (Balanced) Cohorts	850 Participants	1028 Participants

SECONDARY outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure	Secondary Prevention Cohort (Balanced): Apixaban n=7796 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated apixaban on the index date and were balanced using sIPTW method.	Secondary Prevention Cohort (Balanced): Warfarin n=11601 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated warfarin on the index date and were balanced using sIPTW method.
Incidence Rate of Recurrent Cardiogenic Cerebral Embolism During the Follow-up Period: Secondary Prevention (Balanced) Cohorts	10.355 Events Per 1000 Participant-Years Interval 8.043 to 13.332	17.893 Events Per 1000 Participant-Years Interval 15.086 to 21.222

SECONDARY outcome

Timeframe: 0 month, 6 months, 12 months, 18 months and 24 months

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).

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 ".

Outcome measures

Outcome measures
Measure	Secondary Prevention Cohort (Balanced): Apixaban n=7796 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated apixaban on the index date and were balanced using sIPTW method.	Secondary Prevention Cohort (Balanced): Warfarin n=11601 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated warfarin on the index date and were balanced using sIPTW method.
Time Course of Proportion of Incidence of Recurrent Cardiogenic Cerebral Embolism-Free Participants: Secondary Prevention (Balanced) Cohorts 6 Months	0.991 Probability of being event free Interval 0.987 to 0.993	0.989 Probability of being event free Interval 0.985 to 0.992
Time Course of Proportion of Incidence of Recurrent Cardiogenic Cerebral Embolism-Free Participants: Secondary Prevention (Balanced) Cohorts 24 Months	0.981 Probability of being event free Interval 0.975 to 0.986	0.967 Probability of being event free Interval 0.957 to 0.975
Time Course of Proportion of Incidence of Recurrent Cardiogenic Cerebral Embolism-Free Participants: Secondary Prevention (Balanced) Cohorts 0 Month	1.000 Probability of being event free Interval 1.0 to 1.0	1.000 Probability of being event free Interval 1.0 to 1.0
Time Course of Proportion of Incidence of Recurrent Cardiogenic Cerebral Embolism-Free Participants: Secondary Prevention (Balanced) Cohorts 12 Months	0.988 Probability of being event free Interval 0.983 to 0.991	0.981 Probability of being event free Interval 0.974 to 0.986
Time Course of Proportion of Incidence of Recurrent Cardiogenic Cerebral Embolism-Free Participants: Secondary Prevention (Balanced) Cohorts 18 Months	0.984 Probability of being event free Interval 0.978 to 0.988	0.971 Probability of being event free Interval 0.962 to 0.978

SECONDARY outcome

Timeframe: 0 month, 6 months, 12 months, 18 months and 24 months

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).

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".

Outcome measures

Outcome measures
Measure	Secondary Prevention Cohort (Balanced): Apixaban n=7796 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated apixaban on the index date and were balanced using sIPTW method.	Secondary Prevention Cohort (Balanced): Warfarin n=11601 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated warfarin on the index date and were balanced using sIPTW method.
Number of Participants With Risk of Recurrent Cardiogenic Cerebral Embolism: Secondary Prevention (Balanced) Cohorts 0 Month	7796 Participants	11601 Participants
Number of Participants With Risk of Recurrent Cardiogenic Cerebral Embolism: Secondary Prevention (Balanced) Cohorts 6 Months	2088 Participants	2427 Participants
Number of Participants With Risk of Recurrent Cardiogenic Cerebral Embolism: Secondary Prevention (Balanced) Cohorts 12 Months	1460 Participants	1701 Participants
Number of Participants With Risk of Recurrent Cardiogenic Cerebral Embolism: Secondary Prevention (Balanced) Cohorts 18 Months	1119 Participants	1293 Participants
Number of Participants With Risk of Recurrent Cardiogenic Cerebral Embolism: Secondary Prevention (Balanced) Cohorts 24 Months	863 Participants	1047 Participants

SECONDARY outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure	Secondary Prevention Cohort (Balanced): Apixaban n=7796 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated apixaban on the index date and were balanced using sIPTW method.	Secondary Prevention Cohort (Balanced): Warfarin n=11601 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated warfarin on the index date and were balanced using sIPTW method.
Incidence Rate of Recurrent Cerebral Infarction During the Follow-up Period: Secondary Prevention (Balanced) Cohorts	15.481 Events Per 1000 Participant-Years Interval 12.581 to 19.048	13.430 Events Per 1000 Participant-Years Interval 11.026 to 16.358

SECONDARY outcome

Timeframe: 0 month, 6 months, 12 months, 18 months and 24 months

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).

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".

Outcome measures

Outcome measures
Measure	Secondary Prevention Cohort (Balanced): Apixaban n=7796 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated apixaban on the index date and were balanced using sIPTW method.	Secondary Prevention Cohort (Balanced): Warfarin n=11601 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated warfarin on the index date and were balanced using sIPTW method.
Time Course of Proportion of Incidence of Recurrent Cerebral Infarction-Free Participants: Secondary Prevention (Balanced) Cohorts 0 Month	1.000 Probability of being event free Interval 1.0 to 1.0	1.000 Probability of being event free Interval 1.0 to 1.0
Time Course of Proportion of Incidence of Recurrent Cerebral Infarction-Free Participants: Secondary Prevention (Balanced) Cohorts 6 Months	0.990 Probability of being event free Interval 0.987 to 0.992	0.989 Probability of being event free Interval 0.985 to 0.992
Time Course of Proportion of Incidence of Recurrent Cerebral Infarction-Free Participants: Secondary Prevention (Balanced) Cohorts 12 Months	0.981 Probability of being event free Interval 0.976 to 0.986	0.984 Probability of being event free Interval 0.978 to 0.988
Time Course of Proportion of Incidence of Recurrent Cerebral Infarction-Free Participants: Secondary Prevention (Balanced) Cohorts 18 Months	0.976 Probability of being event free Interval 0.97 to 0.982	0.980 Probability of being event free Interval 0.973 to 0.986
Time Course of Proportion of Incidence of Recurrent Cerebral Infarction-Free Participants: Secondary Prevention (Balanced) Cohorts 24 Months	0.973 Probability of being event free Interval 0.965 to 0.979	0.977 Probability of being event free Interval 0.968 to 0.983

SECONDARY outcome

Timeframe: 0 month, 6 months, 12 months, 18 months and 24 months

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).

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".

Outcome measures

Outcome measures
Measure	Secondary Prevention Cohort (Balanced): Apixaban n=7796 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated apixaban on the index date and were balanced using sIPTW method.	Secondary Prevention Cohort (Balanced): Warfarin n=11601 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated warfarin on the index date and were balanced using sIPTW method.
Number of Participants With Risk of Recurrent Cerebral Infarction: Secondary Prevention (Balanced) Cohorts 0 Month	7796 Participants	11601 Participants
Number of Participants With Risk of Recurrent Cerebral Infarction: Secondary Prevention (Balanced) Cohorts 6 Months	2082 Participants	2414 Participants
Number of Participants With Risk of Recurrent Cerebral Infarction: Secondary Prevention (Balanced) Cohorts 12 Months	1447 Participants	1691 Participants
Number of Participants With Risk of Recurrent Cerebral Infarction: Secondary Prevention (Balanced) Cohorts 18 Months	1110 Participants	1293 Participants
Number of Participants With Risk of Recurrent Cerebral Infarction: Secondary Prevention (Balanced) Cohorts 24 Months	856 Participants	1046 Participants

SECONDARY outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure	Secondary Prevention Cohort (Balanced): Apixaban n=7796 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated apixaban on the index date and were balanced using sIPTW method.	Secondary Prevention Cohort (Balanced): Warfarin n=11601 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated warfarin on the index date and were balanced using sIPTW method.
Incidence Rate of Intracranial Hemorrhage During the Follow-up Period: Secondary Prevention (Balanced) Cohorts	38.214 Events Per 1000 Participant-Years Interval 33.476 to 43.623	44.868 Events Per 1000 Participant-Years Interval 40.251 to 50.015

SECONDARY outcome

Timeframe: 0 month, 6 months, 12 months, 18 months and 24 months

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).

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).

Outcome measures

Outcome measures
Measure	Secondary Prevention Cohort (Balanced): Apixaban n=7796 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated apixaban on the index date and were balanced using sIPTW method.	Secondary Prevention Cohort (Balanced): Warfarin n=11601 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated warfarin on the index date and were balanced using sIPTW method.
Time Course of Proportion of Incidence of Intracranial Hemorrhage-Free Participants: Secondary Prevention (Balanced) Cohorts 0 Month	1.000 Probability of being event free Interval 1.0 to 1.0	1.000 Probability of being event free Interval 1.0 to 1.0
Time Course of Proportion of Incidence of Intracranial Hemorrhage-Free Participants: Secondary Prevention (Balanced) Cohorts 6 Months	0.974 Probability of being event free Interval 0.969 to 0.978	0.969 Probability of being event free Interval 0.963 to 0.973
Time Course of Proportion of Incidence of Intracranial Hemorrhage-Free Participants: Secondary Prevention (Balanced) Cohorts 12 Months	0.959 Probability of being event free Interval 0.951 to 0.965	0.958 Probability of being event free Interval 0.95 to 0.965
Time Course of Proportion of Incidence of Intracranial Hemorrhage-Free Participants: Secondary Prevention (Balanced) Cohorts 18 Months	0.952 Probability of being event free Interval 0.943 to 0.959	0.951 Probability of being event free Interval 0.941 to 0.959
Time Course of Proportion of Incidence of Intracranial Hemorrhage-Free Participants: Secondary Prevention (Balanced) Cohorts 24 Months	0.944 Probability of being event free Interval 0.934 to 0.952	0.936 Probability of being event free Interval 0.924 to 0.947

SECONDARY outcome

Timeframe: 0 month, 6 months, 12 months, 18 months and 24 months

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).

In this outcome measure, number of participants with risk of intracranial hemorrhage was reported.

Outcome measures

Outcome measures
Measure	Secondary Prevention Cohort (Balanced): Apixaban n=7796 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated apixaban on the index date and were balanced using sIPTW method.	Secondary Prevention Cohort (Balanced): Warfarin n=11601 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated warfarin on the index date and were balanced using sIPTW method.
Number of Participants With Risk of Intracranial Hemorrhage: Secondary Prevention (Balanced) Cohorts 0 Month	7796 Participants	11601 Participants
Number of Participants With Risk of Intracranial Hemorrhage: Secondary Prevention (Balanced) Cohorts 6 Months	2069 Participants	2401 Participants
Number of Participants With Risk of Intracranial Hemorrhage: Secondary Prevention (Balanced) Cohorts 12 Months	1434 Participants	1675 Participants
Number of Participants With Risk of Intracranial Hemorrhage: Secondary Prevention (Balanced) Cohorts 18 Months	1106 Participants	1279 Participants
Number of Participants With Risk of Intracranial Hemorrhage: Secondary Prevention (Balanced) Cohorts 24 Months	854 Participants	1029 Participants

SECONDARY outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure	Secondary Prevention Cohort (Balanced): Apixaban n=7796 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated apixaban on the index date and were balanced using sIPTW method.	Secondary Prevention Cohort (Balanced): Warfarin n=11601 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated warfarin on the index date and were balanced using sIPTW method.
Incidence Rate of Gastrointestinal Bleeding During the Follow-up Period: Secondary Prevention (Balanced) Cohorts	47.634 Events Per 1000 Participant-Years Interval 42.257 to 53.696	47.876 Events Per 1000 Participant-Years Interval 43.07 to 53.219

SECONDARY outcome

Timeframe: 0 month, 6 months, 12 months, 18 months and 24 months

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).

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).

Outcome measures

Outcome measures
Measure	Secondary Prevention Cohort (Balanced): Apixaban n=7796 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated apixaban on the index date and were balanced using sIPTW method.	Secondary Prevention Cohort (Balanced): Warfarin n=11601 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated warfarin on the index date and were balanced using sIPTW method.
Time Course of Proportion of Incidence of Gastrointestinal Bleeding-Free Participants: Secondary Prevention (Balanced) Cohorts 0 Month	1.000 Probability of being event free Interval 1.0 to 1.0	1.000 Probability of being event free Interval 1.0 to 1.0
Time Course of Proportion of Incidence of Gastrointestinal Bleeding-Free Participants: Secondary Prevention (Balanced) Cohorts 6 Months	0.969 Probability of being event free Interval 0.964 to 0.974	0.968 Probability of being event free Interval 0.962 to 0.974
Time Course of Proportion of Incidence of Gastrointestinal Bleeding-Free Participants: Secondary Prevention (Balanced) Cohorts 12 Months	0.953 Probability of being event free Interval 0.945 to 0.959	0.954 Probability of being event free Interval 0.945 to 0.962
Time Course of Proportion of Incidence of Gastrointestinal Bleeding-Free Participants: Secondary Prevention (Balanced) Cohorts 18 Months	0.931 Probability of being event free Interval 0.92 to 0.941	0.931 Probability of being event free Interval 0.918 to 0.942
Time Course of Proportion of Incidence of Gastrointestinal Bleeding-Free Participants: Secondary Prevention (Balanced) Cohorts 24 Months	0.918 Probability of being event free Interval 0.905 to 0.929	0.915 Probability of being event free Interval 0.899 to 0.928

SECONDARY outcome

Timeframe: 0 month, 6 months, 12 months, 18 months and 24 months

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).

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

Outcome measures

Outcome measures
Measure	Secondary Prevention Cohort (Balanced): Apixaban n=7796 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated apixaban on the index date and were balanced using sIPTW method.	Secondary Prevention Cohort (Balanced): Warfarin n=11601 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated warfarin on the index date and were balanced using sIPTW method.
Number of Participants With Risk of Gastrointestinal Bleeding: Secondary Prevention (Balanced) Cohorts 24 Months	828 Participants	1007 Participants
Number of Participants With Risk of Gastrointestinal Bleeding: Secondary Prevention (Balanced) Cohorts 0 Month	7796 Participants	11601 Participants
Number of Participants With Risk of Gastrointestinal Bleeding: Secondary Prevention (Balanced) Cohorts 6 Months	2047 Participants	2381 Participants
Number of Participants With Risk of Gastrointestinal Bleeding: Secondary Prevention (Balanced) Cohorts 12 Months	1424 Participants	1664 Participants
Number of Participants With Risk of Gastrointestinal Bleeding: Secondary Prevention (Balanced) Cohorts 18 Months	1085 Participants	1257 Participants

SECONDARY outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure	Secondary Prevention Cohort (Balanced): Apixaban n=7796 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated apixaban on the index date and were balanced using sIPTW method.	Secondary Prevention Cohort (Balanced): Warfarin n=11601 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated warfarin on the index date and were balanced using sIPTW method.
Incidence Rate of Intraocular Bleeding During the Follow-up Period: Secondary Prevention (Balanced) Cohorts	3.748 Events Per 1000 Participant-Years Interval 2.463 to 5.704	8.627 Events Per 1000 Participant-Years Interval 6.741 to 11.04

SECONDARY outcome

Timeframe: 0 month, 6 months, 12 months, 18 months and 24 months

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).

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).

Outcome measures

Outcome measures
Measure	Secondary Prevention Cohort (Balanced): Apixaban n=7796 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated apixaban on the index date and were balanced using sIPTW method.	Secondary Prevention Cohort (Balanced): Warfarin n=11601 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated warfarin on the index date and were balanced using sIPTW method.
Time Course of Proportion of Incidence of Intraocular Bleeding-Free Participants: Secondary Prevention (Balanced) Cohorts 0 Month	1.000 Probability of being event free Interval 1.0 to 1.0	1.000 Probability of being event free Interval 1.0 to 1.0
Time Course of Proportion of Incidence of Intraocular Bleeding-Free Participants: Secondary Prevention (Balanced) Cohorts 6 Months	0.998 Probability of being event free Interval 0.996 to 0.999	0.995 Probability of being event free Interval 0.992 to 0.997
Time Course of Proportion of Incidence of Intraocular Bleeding-Free Participants: Secondary Prevention (Balanced) Cohorts 12 Months	0.995 Probability of being event free Interval 0.992 to 0.997	0.991 Probability of being event free Interval 0.986 to 0.994
Time Course of Proportion of Incidence of Intraocular Bleeding-Free Participants: Secondary Prevention (Balanced) Cohorts 18 Months	0.992 Probability of being event free Interval 0.987 to 0.995	0.987 Probability of being event free Interval 0.98 to 0.991
Time Course of Proportion of Incidence of Intraocular Bleeding-Free Participants: Secondary Prevention (Balanced) Cohorts 24 Months	0.991 Probability of being event free Interval 0.986 to 0.995	0.985 Probability of being event free Interval 0.977 to 0.99

SECONDARY outcome

Timeframe: 0 month, 6 months, 12 months, 18 months and 24 months

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).

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

Outcome measures

Outcome measures
Measure	Secondary Prevention Cohort (Balanced): Apixaban n=7796 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated apixaban on the index date and were balanced using sIPTW method.	Secondary Prevention Cohort (Balanced): Warfarin n=11601 Participants Participants with prior diagnosis of stroke who were newly diagnosed with NVAF and initiated warfarin on the index date and were balanced using sIPTW method.
Number of Participants With Risk of Intraocular Bleeding: Secondary Prevention (Balanced) Cohorts 0 Month	7796 Participants	11601 Participants
Number of Participants With Risk of Intraocular Bleeding: Secondary Prevention (Balanced) Cohorts 6 Months	2097 Participants	2428 Participants
Number of Participants With Risk of Intraocular Bleeding: Secondary Prevention (Balanced) Cohorts 12 Months	1462 Participants	1691 Participants
Number of Participants With Risk of Intraocular Bleeding: Secondary Prevention (Balanced) Cohorts 18 Months	1118 Participants	1285 Participants
Number of Participants With Risk of Intraocular Bleeding: Secondary Prevention (Balanced) Cohorts 24 Months	863 Participants	1040 Participants

Adverse Events

Secondary Prevention Cohort: Apixaban

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Secondary Prevention Cohort: Warfarin

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

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Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Publication restrictions are in place

Restriction type: OTHER