Non-valvular Atrial FibrillationNCT05321810

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

An observational study of Non-valvular Atrial Fibrillation, run by Pfizer at 1 site in Japan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial 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… Read more about this study

Who is it for?: Ages 20 years and older
Conditions the study is for: Non-valvular Atrial Fibrillation
What is being tested?: Apixaban and Warfarin
How many people: 193,565 participants
Where: 1 siteJapan
Study dates: 15 Apr 2022to 15 Apr 2022
Phase: Observational
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 20 years and older
All sexes
No healthy volunteers
Adult, Older adult

Study population: Secondary prevention patients who are newly diagnosed with NVAF and initiate anticoagulation therapy with warfarin or apixaban.

Who may be able to join

Patients must meet all the following selection criteria
Patients registered in the Medical Data Vision (MDV) database 2008 though 2021.
Patients newly with non-valvular atrial fibrillation
Patients who newly receive warfarin or apixaban after diagnosis of NVAF
Age 20 years or older on the index date
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.

Who cannot join

Patients who meet the following exclusion criteria will be excluded from this study
Patients with a diagnosis of valvular AF (standard disease code: 8846941), postoperative AF (8847772), AF associated with mechanical valve malfunction (T82.0), mechanical complication of heart valve prosthesis (T82.0), or rheumatic AF (I05-I09) during the baseline period.
Patients with a diagnosis of venous thromboembolism (VTE) during the baseline period
Patients who are prescribed any anticoagulants before index date.
Patients who are prescribed anticoagulants other than warfarin and apixaban on the index date
Patients who are continuously hospitalized due to the first incidence of stroke or other serious diseases.

Trial locations and contacts

1 site in 1 country.

Japan1 site

Pfizer
Tokyo

Other trials in Japan

About this study

Official title: 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

Read the 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.

Conditions: Non-valvular Atrial Fibrillation
Being tested: Apixaban, Warfarin
Keywords: Non-valvular atrial fibrillation, Stroke, Apixaban, Warfarin, Secondary prevention
Medical subject headings: Stroke

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

Study groups in NCT05321810
Study group	Role	What they receive
Warfarin cohort (Reference)		Patients with NVAF treated with warfarin Receives: Drug: Warfarin
Apixaban cohort		Patients with NVAF treated with apixaban Receives: Drug: Apixaban

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: During follow up period (Data collected between 2008 to 2021 [approximately 13 years])
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".
Measured: 0 month
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".
Measured: 6 months
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".
Measured: 12 months
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".
Measured: 18 months
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".
Measured: 24 months
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".
Measured: 0 month
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".
Measured: 6 months
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".
Measured: 12 months
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".
Measured: 18 months
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".
Measured: 24 months
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.
Measured: During follow up period (Data collected between 2008 to 2021 [approximately 13 years])
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).
Measured: 0 month
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).
Measured: 6 months
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).
Measured: 12 months
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).
Measured: 18 months
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).
Measured: 24 months
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).
Measured: 0 month
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).
Measured: 6 months
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).
Measured: 12 months
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).
Measured: 18 months
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).
Measured: 24 months

Secondary outcomes (15)

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.
Measured: During follow up period (Data collected between 2008 to 2021 [approximately 13 years])
Time Course of Proportion of Incidence of Recurrent Cardiogenic Cerebral Embolism-Free Participants: Secondary Prevention (Balanced) Cohorts
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 ".
Measured: 0 month, 6 months, 12 months, 18 months and 24 months
Number of Participants With Risk of Recurrent Cardiogenic Cerebral Embolism: Secondary Prevention (Balanced) Cohorts
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".
Measured: 0 month, 6 months, 12 months, 18 months and 24 months
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.
Measured: During Follow up period (Data collected between 2008 to 2021 [approximately 13 years])
Time Course of Proportion of Incidence of Recurrent Cerebral Infarction-Free Participants: Secondary Prevention (Balanced) Cohorts
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".
Measured: 0 month, 6 months, 12 months, 18 months and 24 months
Number of Participants With Risk of Recurrent Cerebral Infarction: Secondary Prevention (Balanced) Cohorts
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".
Measured: 0 month, 6 months, 12 months, 18 months and 24 months
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.
Measured: During follow up period (Data collected between 2008 to 2021 [approximately 13 years])
Time Course of Proportion of Incidence of Intracranial Hemorrhage-Free Participants: Secondary Prevention (Balanced) Cohorts
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).
Measured: 0 month, 6 months, 12 months, 18 months and 24 months
Number of Participants With Risk of Intracranial Hemorrhage: Secondary Prevention (Balanced) Cohorts
In this outcome measure, number of participants with risk of intracranial hemorrhage was reported.
Measured: 0 month, 6 months, 12 months, 18 months and 24 months
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.
Measured: During follow up period (Data collected between 2008 to 2021 [approximately 13 years])
Time Course of Proportion of Incidence of Gastrointestinal Bleeding-Free Participants: Secondary Prevention (Balanced) Cohorts
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).
Measured: 0 month, 6 months, 12 months, 18 months and 24 months
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.
Measured: 0 month, 6 months, 12 months, 18 months and 24 months
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.
Measured: During follow up period (Data collected between 2008 to 2021 [approximately 13 years])
Time Course of Proportion of Incidence of Intraocular Bleeding-Free Participants: Secondary Prevention (Balanced) Cohorts
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).
Measured: 0 month, 6 months, 12 months, 18 months and 24 months
Number of Participants With Risk of Intraocular Bleeding: Secondary Prevention (Balanced) Cohorts
In this outcome measure, number of participants with risk of intraocular bleeding was reported.
Measured: 0 month, 6 months, 12 months, 18 months and 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

15 Apr 202215 Apr 2022

First posted11 Apr 2022
Study start15 Apr 2022
Primary completion15 Apr 2022
Study completion15 Apr 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Non-valvular Atrial FibrillationStudies of the same condition, open and under way.
More trials run by PfizerThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Observational
Observational model: Cohort
Time perspective: Retrospective
Enrolment: 193,565 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05321810
Sponsor's protocol ID: B0661176
Other IDs: Secondary prevention
Status last verified: Mar 2023
First submitted: 3 Apr 2022
Last updated: 11 Jan 2024
Results posted: Yes, on ClinicalTrials.gov
Individual data sharing: No: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Non Valvular Atrial Fibrillation

All Non-valvular Atrial Fibrillation trials

Study at a glance

From the registry record, last updated by the sponsor on 11 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: 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
ClinicalTrials.gov ID: NCT05321810
Acronym / sponsor ID: B0661176
Conditions: Non-valvular Atrial Fibrillation
Keywords: Non-valvular atrial fibrillation, Stroke, Apixaban, Warfarin, Secondary prevention
Study type: Observational
Recruitment status: Completed
Enrolment: 193,565 participants (actual)
Lead sponsor: PfizerIndustry (pharma, biotech, devices)
Study start: 15 Apr 2022 (actual)
Primary completion: 15 Apr 2022 (actual)
Study completion: 15 Apr 2022 (actual)
First posted: 11 Apr 2022 (actual)
Results: Posted 11 Jan 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

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.

Study design

Observational model: Cohort
Time perspective: Retrospective
Number of arms: 2

Arm	Type	Receives
Warfarin cohort (Reference)	–	Drug: WarfarinPatients with NVAF treated with warfarin
Apixaban cohort	–	Drug: ApixabanPatients with NVAF treated with apixaban

Who may qualify

Ages: 20 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult
Study population: Secondary prevention patients who are newly diagnosed with NVAF and initiate anticoagulation therapy with warfarin or apixaban.

Key inclusion criteria (6 listed)

Patients must meet all the following selection criteria
Patients registered in the Medical Data Vision (MDV) database 2008 though 2021.
Patients newly with non-valvular atrial fibrillation
Patients who newly receive warfarin or apixaban after diagnosis of NVAF
Age 20 years or older on the index date

Key exclusion criteria (6 listed)

Patients who meet the following exclusion criteria will be excluded from this study
Patients with a diagnosis of valvular AF (standard disease code: 8846941), postoperative AF (8847772), AF associated with mechanical valve malfunction (T82.0), mechanical complication of heart valve prosthesis (T82.0), or rheumatic AF (I05-I09) during the baseline period.
Patients with a diagnosis of venous thromboembolism (VTE) during the baseline period
Patients who are prescribed any anticoagulants before index date.
Patients who are prescribed anticoagulants other than warfarin and apixaban on the index date

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
ApixabanThis is observational study and the patients in the apixaban cohort include those who are exposed to apixaban in the real world settings.	Drug	Apixaban cohort
WarfarinThis is observational study and the patients in the warfarin cohort include those who are exposed to warfarin in the real world settings.	Drug	Warfarin cohort (Reference)

Primary outcome

Incidence Rate of a Composite of Recurrent Stroke or Systemic Embolism (SE) During the Follow-up Period: Secondary Prevention (Balanced) Cohort
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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".
Number of Participants With Risk of a Composite of Recurrent Stroke or SE at 0 Month: Secondary Prevention (Balanced) Cohorts
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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).
Number of Participants With Risk of Major Bleeding at 24 Months: Secondary Prevention (Balanced) Cohorts
Time frame: 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).

15 secondary outcomes

Incidence Rate of Recurrent Cardiogenic Cerebral Embolism During the Follow-up Period: Secondary Prevention (Balanced) Cohorts
Time frame: During follow up period (Data collected between 2008 to 2021 [approximately 13 years])
Time Course of Proportion of Incidence of Recurrent Cardiogenic Cerebral Embolism-Free Participants: Secondary Prevention (Balanced) Cohorts
Time frame: 0 month, 6 months, 12 months, 18 months and 24 months
Number of Participants With Risk of Recurrent Cardiogenic Cerebral Embolism: Secondary Prevention (Balanced) Cohorts
Time frame: 0 month, 6 months, 12 months, 18 months and 24 months
Incidence Rate of Recurrent Cerebral Infarction During the Follow-up Period: Secondary Prevention (Balanced) Cohorts
Time frame: During Follow up period (Data collected between 2008 to 2021 [approximately 13 years])
Time Course of Proportion of Incidence of Recurrent Cerebral Infarction-Free Participants: Secondary Prevention (Balanced) Cohorts
Time frame: 0 month, 6 months, 12 months, 18 months and 24 months
Number of Participants With Risk of Recurrent Cerebral Infarction: Secondary Prevention (Balanced) Cohorts
Time frame: 0 month, 6 months, 12 months, 18 months and 24 months
Incidence Rate of Intracranial Hemorrhage During the Follow-up Period: Secondary Prevention (Balanced) Cohorts
Time frame: During follow up period (Data collected between 2008 to 2021 [approximately 13 years])
Time Course of Proportion of Incidence of Intracranial Hemorrhage-Free Participants: Secondary Prevention (Balanced) Cohorts
Time frame: 0 month, 6 months, 12 months, 18 months and 24 months
Number of Participants With Risk of Intracranial Hemorrhage: Secondary Prevention (Balanced) Cohorts
Time frame: 0 month, 6 months, 12 months, 18 months and 24 months
Incidence Rate of Gastrointestinal Bleeding During the Follow-up Period: Secondary Prevention (Balanced) Cohorts
Time frame: During follow up period (Data collected between 2008 to 2021 [approximately 13 years])
Time Course of Proportion of Incidence of Gastrointestinal Bleeding-Free Participants: Secondary Prevention (Balanced) Cohorts
Time frame: 0 month, 6 months, 12 months, 18 months and 24 months
Number of Participants With Risk of Gastrointestinal Bleeding: Secondary Prevention (Balanced) Cohorts
Time frame: 0 month, 6 months, 12 months, 18 months and 24 months
Incidence Rate of Intraocular Bleeding During the Follow-up Period: Secondary Prevention (Balanced) Cohorts
Time frame: During follow up period (Data collected between 2008 to 2021 [approximately 13 years])
Time Course of Proportion of Incidence of Intraocular Bleeding-Free Participants: Secondary Prevention (Balanced) Cohorts
Time frame: 0 month, 6 months, 12 months, 18 months and 24 months
Number of Participants With Risk of Intraocular Bleeding: Secondary Prevention (Balanced) Cohorts
Time frame: 0 month, 6 months, 12 months, 18 months and 24 months

Results and safety

Results posted to the registry on 11 Jan 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Primary Prevention Cohort: Apixaban	57,560	57,560
Primary Prevention Cohort: Warfarin	90,636	90,636
Secondary Prevention Cohort: Apixaban	18,216	18,216
Secondary Prevention Cohort: Warfarin	27,153	27,153

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

Time frame: During follow up period (Data collected between 2008 to 2021 [approximately 13 years]). Number (95% Confidence Interval). Unit: Events Per 1000 Participant-Years

Measure	Secondary Prevention Cohort (Balanced): Apixaban n = 7796	Secondary Prevention Cohort (Balanced): Warfarin n = 11601
Value	41.217 (36.274 to 46.834)	50.581 (45.658 to 56.034)

Population analysed: 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).

Primary outcome: 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

Time frame: 0 month. Number (95% Confidence Interval). Unit: Probability of being event free

Measure	Secondary Prevention Cohort (Balanced): Apixaban n = 7796	Secondary Prevention Cohort (Balanced): Warfarin n = 11601
Value	1.000 (1.000 to 1.000)	1.000 (1.000 to 1.000)

Primary outcome: 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

Time frame: 6 months. Number (95% Confidence Interval). Unit: Probability of being event free

Measure	Secondary Prevention Cohort (Balanced): Apixaban n = 7796	Secondary Prevention Cohort (Balanced): Warfarin n = 11601
Value	0.971 (0.966 to 0.976)	0.967 (0.961 to 0.972)

Primary outcome: 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

Time frame: 12 months. Number (95% Confidence Interval). Unit: Probability of being event free

Measure	Secondary Prevention Cohort (Balanced): Apixaban n = 7796	Secondary Prevention Cohort (Balanced): Warfarin n = 11601
Value	0.953 (0.946 to 0.960)	0.948 (0.938 to 0.956)

15 secondary outcomes are reported in the full results.

Adverse events

Time frame: Not applicable as safety data were not collected during the study.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Secondary Prevention Cohort: Apixaban	0 of 0	0 of 0	0
Secondary Prevention Cohort: Warfarin	0 of 0	0 of 0	0

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 11 Jan 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
To obtain contact information for a study center near you, click here.Link provided by the sponsor.
Individual participant dataSharing planned: No. Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Pfizer CT.gov Call Center study director

Pfizer

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

An observational study of Non-valvular Atrial Fibrillation, run by Pfizer at 1 site in Japan.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 11 Jan 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence Rate of a Composite of Recurrent Stroke or Systemic Embolism (SE) During the Follow-up Period: Secondary Prevention (Balanced) Cohort (time frame: During follow up period (Data collected between 2008 to 2021 [approximately 13 years])). The study lists 22 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05321810.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jan 2024.