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

Non-valvular Atrial Fibrillation Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05321810
• Other study ID #: B0661176
• Secondary ID: Secondary preven
• Status: Completed
• Start date: April 15, 2022
• Est. completion date: April 15, 2022

Study information

• Verified date: March 2023
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical 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 compared to warfarin in patients with non-valvular atrial fibrillation (NVAF).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 193565
• Est. completion date: April 15, 2022
• Est. primary completion date: April 15, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

Inclusion Criteria:

Patients must meet all the following selection criteria

1. Patients registered in the Medical Data Vision (MDV) database 2008 though 2021.

2. Patients newly with non-valvular atrial fibrillation

3. Patients who newly receive warfarin or apixaban after diagnosis of NVAF

4. Age 20 years or older on the index date

5. Patients who have a history of stroke or transient ischemic attack (TIA) are inclusion criteria only for secondary prevention cohort, otherwise patients will be concluded in the primary prevention cohort. Exclusion Criteria: Patients who meet the following 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.

Related Conditions & MeSH terms

• Atrial Fibrillation
• Non-valvular Atrial Fibrillation

Intervention

Drug:
• Apixaban
This is observational study and the patients in the apixaban cohort include those who are exposed to apixaban in the real world settings.
• Warfarin
This is observational study and the patients in the warfarin cohort include those who are exposed to warfarin in the real world settings.

Locations

Country	Name	City	State
Japan	Pfizer	Tokyo

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

Japan, 

Outcome

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

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