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

Completed

• Conditions: Non-valvular Atrial Fibrillation
• Interventions: Drug: Warfarin; Drug: Apixaban

• Registration Number: NCT05321810
• Lead Sponsor: Pfizer

Brief Summary

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

Detailed Description

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

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

Study Timeline

• Study First Submitted: 2022-04-03
• Study First Submitted QC: 2022-04-03
• Study First Posted: 2022-04-11
• Study Start: 2022-04-15
• Primary Completion: 2022-04-15
• Study Completion: 2022-04-15
• Status Verified: 2023-03
• Results First Submitted: 2023-03-29
• Results First Submitted QC: 2023-03-29
• Last Update Submitted: 2023-03-29
• Results First Posted: 2024-01-11
• Last Update Posted: 2024-01-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 193565

Inclusion Criteria

Patients must meet all the following selection criteria

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

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Exclusion Criteria

Patients who meet the following exclusion criteria will be excluded from this study

1. 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.
2. Patients with a diagnosis of venous thromboembolism (VTE) during the baseline period
3. Patients who are prescribed any anticoagulants before index date.
4. Patients who are prescribed anticoagulants other than warfarin and apixaban on the index date
5. Patients who are continuously hospitalized due to the first incidence of stroke or other serious diseases.

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Warfarin cohort (Reference)	Warfarin	Patients with NVAF treated with warfarin
Apixaban cohort	Apixaban	Patients with NVAF treated with apixaban

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Pfizer; 🇯🇵 Tokyo, Japan