Non-valvular Atrial Fibrillation
Conditions
Brief summary
* The purpose of this study is to compare effectiveness and safety of warfarin and apixaban among non-valvular atrial fibrillation (NVAF) patients at higher chance of bleeding using a Japanese nation-wide administrative claims database. * Atrial fibrillation (AF) is characterized by a fast, irregular heartbeat which can cause blood to pool in the atria and increase the chance of the formation of blood clots. * An anticoagulation therapy is a critical treatment to prevent thromboembolism in NVAF patients. * Apixaban was demonstrated superiority compared to warfarin in preventing stroke or systemic embolism, caused less bleeding, and resulted in lower mortality in patients with AF in Phase 3 clinical trial. * Previously we have shown that bleeding risks as well as stroke/SE risks are less in real world clinical practice in Japan compared to warfarin. However there are limited apixaban data for Japanese NVAF patients with high bleeding risk(s). * This study will evaluate the risk of stroke/systemic embolism as well as the risk of bleeding in the real world settings in Japanese patients with NVAF who has higher chance of bleeding
Interventions
None listed
Sponsors
Pfizer
Study design
Observational model
OTHER
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosed with atrial fibrillation (AF) anytime in the baseline period or on the index date, also have definitive diagnosis of AF anytime in the baseline period, on the index date, or post-index period. * Prescribed apixaban or warfarin on or after the day of AF diagnosis. The first observed prescription will be used to identify the patient's index date and treatment cohort * No use of the any oral anticoagulants (OACs) during the baseline period (the 180 days before the index date) * Age of 18 years or older on the index date
Exclusion criteria
* Having a diagnosis of valvular atrial fibrillation, post-operative atrial fibrillation, rheumatic atrial fibrillation or mechanical-valvular atrial fibrillation during the baseline and post-index period * Having a procedure of prosthetic heart valve during the baseline period * Having a cardiac surgery procedure record during the baseline period * Having a diagnosis of venous thromboembolism during the baseline period * Having a hemodialysis during the baseline period * Female patients with pregnancy during the baseline and follow-up period * Patients prescribed apixaban other than approved daily dose (\<5 mg or \>10 mg) * Patients prescribed OACs during baseline period
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence Rate Per 1000 Participant-Years For First Occurrence of Composite Stroke and Systemic Embolism (SE) Events After Index Date: Balanced Cohorts | Follow-up period during data observation period from Mar 2011 to Jun 2021 (approximately 10 years 4 months); extracted data evaluated in approximately 1 month of this study | Incidence rate per 1000 participant-years for the first occurrence of composite stroke and SE events after index date was reported. Stroke events included the composite of any ischemic and any hemorrhagic stroke events (excluding non-traumatic extradural hemorrhage). Stroke after index date not including the index date was identified using hospital claims which had a stroke diagnosis code as the first listed International Classification of Diseases 10th Revision (ICD-10) diagnosis code. SE after index date not including the index date was identified using hospital claims which had a SE diagnosis code as the first listed ICD-10 diagnosis code. Index date: date when participants initiated warfarin or apixaban. Follow-up period: from next day of the index date till occurrence of target outcome event, discontinuation of apixaban or warfarin; switching from apixaban or warfarin; withdrawal from the database, whichever occurred first. |
| Incidence Rate Per 1000 Participant-Years For First Occurrence of Major Bleeding Event After Index Date: Balanced Cohorts | Follow-up period during data observation period from Mar 2011 to Jun 2021 (approximately 10 years 4 months); extracted data evaluated in approximately 1 month of this study | Incidence rate per 1000 participant-years for the first occurrence of major bleeding event after index date was reported. Major bleeding was defined as any bleeding that required hospitalization for treatment. Major bleeding after index date was identified using hospital claims which had a bleeding diagnosis code as the first listed ICD-10 or disease code. Index date: date when participants initiated warfarin or apixaban. Follow-up period: from next day of the index date till occurrence of target outcome event, discontinuation of apixaban or warfarin; switching from apixaban or warfarin; withdrawal from the database, whichever occurred first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence Rate Per 1000 Participant-Years For First Occurrence of Systemic Embolism (SE) Event After Index Date: Balanced Cohorts | Follow-up period during data observation period from Mar 2011 to Jun 2021 (approximately 10 years 4 months); extracted data evaluated in approximately 1 month of this study | Incidence rate per 1000 participant-years for the first occurrence of SE event after index date was reported. SE after index date not including the index date was identified using hospital claims which had a SE diagnosis code as the first listed ICD-10 diagnosis code. Index date: date when participants initiated warfarin or apixaban. Follow-up period: from next day of the index date till occurrence of target outcome event, discontinuation of apixaban or warfarin; switching from apixaban or warfarin; withdrawal from the database, whichever occurred first. |
| Incidence Rate Per 1000 Participant-Years For First Occurrence of Ischemic Stroke Event After Index Date: Balanced Cohorts | Follow-up period during data observation period from Mar 2011 to Jun 2021 (approximately 10 years 4 months); extracted data evaluated in approximately 1 month of this study | Incidence rate per 1000 participant-years for the first occurrence of ischemic stroke event after index date was reported. Ischemic stroke after index date not including the index date was identified using hospital claims which had an ischemic stroke diagnosis code as the first listed ICD-10 diagnosis code. Index date: date when participants initiated warfarin or apixaban. Follow-up period: from next day of the index date till occurrence of target outcome event, discontinuation of apixaban or warfarin; switching from apixaban or warfarin; withdrawal from the database, whichever occurred first. |
| Incidence Rate Per 1000 Participant-Years For First Occurrence of Major Gastrointestinal (GI) Bleeding Event After Index Date: Balanced Cohorts | Follow-up period during data observation period from Mar 2011 to Jun 2021 (approximately 10 years 4 months); extracted data evaluated in approximately 1 month of this study | Incidence rate per 1000 participant-years for the first occurrence of major GI bleeding event after index date was reported. Any GI bleeding after index date was identified using hospital claims which had a GI bleeding diagnosis code as the first listed ICD-10 or disease code. Index date: date when participants initiated warfarin or apixaban. Follow-up period: from next day of the index date till occurrence of target outcome event, discontinuation of apixaban or warfarin; switching from apixaban or warfarin; withdrawal from the database, whichever occurred first. |
| Incidence Rate Per 1000 Participant-Years For First Occurrence of Major Intracranial Bleeding Event After Index Date: Balanced Cohorts | Follow-up period during data observation period from Mar 2011 to Jun 2021 (approximately 10 years 4 months); extracted data evaluated in approximately 1 month of this study | Incidence rate per 1000 participant-years for the first occurrence of major intracranial bleeding event after index date was reported. Major intracranial bleeding after index date was identified using hospital claims which had an intracranial bleeding diagnosis code as the first listed ICD-10 or disease code. Index date: date when participants initiated warfarin or apixaban. Follow-up period: from next day of the index date till occurrence of target outcome event, discontinuation of apixaban or warfarin; switching from apixaban or warfarin; withdrawal from the database, whichever occurred first. |
| Incidence Rate Per 1000 Participant-Years For First Occurrence of Hemorrhagic Stroke Event After Index Date: Balanced Cohorts | Follow-up period during data observation period from Mar 2011 to Jun 2021 (approximately 10 years 4 months); extracted data evaluated in approximately 1 month of this study | Incidence rate per 1000 participant-years for the first occurrence of hemorrhagic stroke event after index date was reported. Hemorrhagic stroke after index date not including the index date was identified using hospital claims which had a hemorrhagic stroke diagnosis code as the first listed ICD-10 diagnosis code. Index date: date when participants initiated warfarin or apixaban. Follow-up period: from next day of the index date till occurrence of target outcome event, discontinuation of apixaban or warfarin; switching from apixaban or warfarin; withdrawal from the database, whichever occurred first. |
Countries
Japan
Participant flow
Recruitment details
Data of participants diagnosed with non-valvular atrial fibrillation (NVAF) who were newly prescribed apixaban or warfarin with at least one high bleeding risk factor were observed in this retrospective observational study.
Pre-assignment details
Data of eligible participants were extracted from Medical Data Vision Company Limited (MDV Co. Ltd.) database for duration of 01-Mar-2011 to 30-Jun-2021. Extracted data was evaluated for objectives of this study in approximately 1 month of this study.
Participants by arm
| Arm | Count |
|---|---|
| Apixaban Participants diagnosed with NVAF, who newly initiated apixaban, were included in this cohort. Data from 01-Mar-2011 to 30-Jun-2021, available in MDV database was observed retrospectively. | 72,095 |
| Warfarin Participants diagnosed with NVAF, who newly initiated warfarin, were included in this cohort. Data from 01-Mar-2011 to 30-Jun-2021, available in MDV database was observed retrospectively. | 48,627 |
| Total | 120,722 |
Baseline characteristics
| Characteristic | Warfarin | Total | Apixaban |
|---|---|---|---|
| Age, Customized <= 64 years | 4030 Participants | 8501 Participants | 4471 Participants |
| Age, Customized 65-69 years | 3855 Participants | 8833 Participants | 4978 Participants |
| Age, Customized 70-79 years | 14749 Participants | 35370 Participants | 20621 Participants |
| Age, Customized 80-89 years | 20677 Participants | 54244 Participants | 33567 Participants |
| Age, Customized =>90 years | 5316 Participants | 13774 Participants | 8458 Participants |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Sex: Female, Male Female | 19856 Participants | 51642 Participants | 31786 Participants |
| Sex: Female, Male Male | 28771 Participants | 69080 Participants | 40309 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
Incidence Rate Per 1000 Participant-Years For First Occurrence of Composite Stroke and Systemic Embolism (SE) Events After Index Date: Balanced Cohorts
Incidence rate per 1000 participant-years for the first occurrence of composite stroke and SE events after index date was reported. Stroke events included the composite of any ischemic and any hemorrhagic stroke events (excluding non-traumatic extradural hemorrhage). Stroke after index date not including the index date was identified using hospital claims which had a stroke diagnosis code as the first listed International Classification of Diseases 10th Revision (ICD-10) diagnosis code. SE after index date not including the index date was identified using hospital claims which had a SE diagnosis code as the first listed ICD-10 diagnosis code. Index date: date when participants initiated warfarin or apixaban. Follow-up period: from next day of the index date till occurrence of target outcome event, discontinuation of apixaban or warfarin; switching from apixaban or warfarin; withdrawal from the database, whichever occurred first.
Time frame: Follow-up period during data observation period from Mar 2011 to Jun 2021 (approximately 10 years 4 months); extracted data evaluated in approximately 1 month of this study
Population: Eligible participants registered on MDV database, whose data was observed in the study. Analysis performed using Inverse probability treatment weighting (IPTW) method to balance participant characteristics among reporting groups. Here, Overall Number of Participants Analyzed is the number of participants after application of IPTW method to raw numbers and is different from the actual participants included in the reporting arm.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban: Balanced Cohort | Incidence Rate Per 1000 Participant-Years For First Occurrence of Composite Stroke and Systemic Embolism (SE) Events After Index Date: Balanced Cohorts | 61.352 Events Per 1000 Participant-Years |
| Warfarin: Balanced Cohort | Incidence Rate Per 1000 Participant-Years For First Occurrence of Composite Stroke and Systemic Embolism (SE) Events After Index Date: Balanced Cohorts | 75.078 Events Per 1000 Participant-Years |
p-value: <0.00195% CI: [0.719, 0.787]COX Proportional Hazards Regression
Primary
Incidence Rate Per 1000 Participant-Years For First Occurrence of Major Bleeding Event After Index Date: Balanced Cohorts
Incidence rate per 1000 participant-years for the first occurrence of major bleeding event after index date was reported. Major bleeding was defined as any bleeding that required hospitalization for treatment. Major bleeding after index date was identified using hospital claims which had a bleeding diagnosis code as the first listed ICD-10 or disease code. Index date: date when participants initiated warfarin or apixaban. Follow-up period: from next day of the index date till occurrence of target outcome event, discontinuation of apixaban or warfarin; switching from apixaban or warfarin; withdrawal from the database, whichever occurred first.
Time frame: Follow-up period during data observation period from Mar 2011 to Jun 2021 (approximately 10 years 4 months); extracted data evaluated in approximately 1 month of this study
Population: Eligible participants registered on MDV database, whose data was observed in the study. Analysis performed using IPTW method to balance participant characteristics among reporting groups. Here, Overall Number of Participants Analyzed is the number of participants after application of IPTW method to raw numbers and is different from the actual participants included in the reporting arm.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban: Balanced Cohort | Incidence Rate Per 1000 Participant-Years For First Occurrence of Major Bleeding Event After Index Date: Balanced Cohorts | 16.788 Events Per 1000 Participant-Years |
| Warfarin: Balanced Cohort | Incidence Rate Per 1000 Participant-Years For First Occurrence of Major Bleeding Event After Index Date: Balanced Cohorts | 21.329 Events Per 1000 Participant-Years |
p-value: <0.00195% CI: [0.687, 0.813]COX Proportional Hazards Regression
Secondary
Incidence Rate Per 1000 Participant-Years For First Occurrence of Hemorrhagic Stroke Event After Index Date: Balanced Cohorts
Incidence rate per 1000 participant-years for the first occurrence of hemorrhagic stroke event after index date was reported. Hemorrhagic stroke after index date not including the index date was identified using hospital claims which had a hemorrhagic stroke diagnosis code as the first listed ICD-10 diagnosis code. Index date: date when participants initiated warfarin or apixaban. Follow-up period: from next day of the index date till occurrence of target outcome event, discontinuation of apixaban or warfarin; switching from apixaban or warfarin; withdrawal from the database, whichever occurred first.
Time frame: Follow-up period during data observation period from Mar 2011 to Jun 2021 (approximately 10 years 4 months); extracted data evaluated in approximately 1 month of this study
Population: Eligible participants registered on MDV database, whose data was observed in the study. Analysis performed using IPTW method to balance participant characteristics among reporting groups. Here, Overall Number of Participants Analyzed is the number of participants after application of IPTW method to raw numbers and is different from the actual participants included in the reporting arm.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban: Balanced Cohort | Incidence Rate Per 1000 Participant-Years For First Occurrence of Hemorrhagic Stroke Event After Index Date: Balanced Cohorts | 9.384 Events Per 1000 Participant-Years |
| Warfarin: Balanced Cohort | Incidence Rate Per 1000 Participant-Years For First Occurrence of Hemorrhagic Stroke Event After Index Date: Balanced Cohorts | 9.266 Events Per 1000 Participant-Years |
p-value: 0.37895% CI: [0.842, 1.067]COX Proportional Hazards Regression
Secondary
Incidence Rate Per 1000 Participant-Years For First Occurrence of Ischemic Stroke Event After Index Date: Balanced Cohorts
Incidence rate per 1000 participant-years for the first occurrence of ischemic stroke event after index date was reported. Ischemic stroke after index date not including the index date was identified using hospital claims which had an ischemic stroke diagnosis code as the first listed ICD-10 diagnosis code. Index date: date when participants initiated warfarin or apixaban. Follow-up period: from next day of the index date till occurrence of target outcome event, discontinuation of apixaban or warfarin; switching from apixaban or warfarin; withdrawal from the database, whichever occurred first.
Time frame: Follow-up period during data observation period from Mar 2011 to Jun 2021 (approximately 10 years 4 months); extracted data evaluated in approximately 1 month of this study
Population: Eligible participants registered on MDV database, whose data was observed in the study. Analysis performed using IPTW method to balance participant characteristics among reporting groups. Here, Overall Number of Participants Analyzed is the number of participants after application of IPTW method to raw numbers and is different from the actual participants included in the reporting arm.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban: Balanced Cohort | Incidence Rate Per 1000 Participant-Years For First Occurrence of Ischemic Stroke Event After Index Date: Balanced Cohorts | 49.038 Events Per 1000 Participant-Years |
| Warfarin: Balanced Cohort | Incidence Rate Per 1000 Participant-Years For First Occurrence of Ischemic Stroke Event After Index Date: Balanced Cohorts | 48.917 Events Per 1000 Participant-Years |
p-value: <0.00195% CI: [0.862, 0.958]COX Proportional Hazards Regression
Secondary
Incidence Rate Per 1000 Participant-Years For First Occurrence of Major Gastrointestinal (GI) Bleeding Event After Index Date: Balanced Cohorts
Incidence rate per 1000 participant-years for the first occurrence of major GI bleeding event after index date was reported. Any GI bleeding after index date was identified using hospital claims which had a GI bleeding diagnosis code as the first listed ICD-10 or disease code. Index date: date when participants initiated warfarin or apixaban. Follow-up period: from next day of the index date till occurrence of target outcome event, discontinuation of apixaban or warfarin; switching from apixaban or warfarin; withdrawal from the database, whichever occurred first.
Time frame: Follow-up period during data observation period from Mar 2011 to Jun 2021 (approximately 10 years 4 months); extracted data evaluated in approximately 1 month of this study
Population: Eligible participants registered on MDV database, whose data was observed in the study. Analysis performed using IPTW method to balance participant characteristics among reporting groups. Here, Overall Number of Participants Analyzed is the number of participants after application of IPTW method to raw numbers and is different from the actual participants included in the reporting arm.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban: Balanced Cohort | Incidence Rate Per 1000 Participant-Years For First Occurrence of Major Gastrointestinal (GI) Bleeding Event After Index Date: Balanced Cohorts | 36.836 Events Per 1000 Participant-Years |
| Warfarin: Balanced Cohort | Incidence Rate Per 1000 Participant-Years For First Occurrence of Major Gastrointestinal (GI) Bleeding Event After Index Date: Balanced Cohorts | 36.943 Events Per 1000 Participant-Years |
p-value: 0.02295% CI: [0.877, 0.99]COX Proportional Hazards Regression
Secondary
Incidence Rate Per 1000 Participant-Years For First Occurrence of Major Intracranial Bleeding Event After Index Date: Balanced Cohorts
Incidence rate per 1000 participant-years for the first occurrence of major intracranial bleeding event after index date was reported. Major intracranial bleeding after index date was identified using hospital claims which had an intracranial bleeding diagnosis code as the first listed ICD-10 or disease code. Index date: date when participants initiated warfarin or apixaban. Follow-up period: from next day of the index date till occurrence of target outcome event, discontinuation of apixaban or warfarin; switching from apixaban or warfarin; withdrawal from the database, whichever occurred first.
Time frame: Follow-up period during data observation period from Mar 2011 to Jun 2021 (approximately 10 years 4 months); extracted data evaluated in approximately 1 month of this study
Population: Eligible participants registered on MDV database, whose data was observed in the study. Analysis performed using IPTW method to balance participant characteristics among reporting groups. Here, Overall Number of Participants Analyzed is the number of participants after application of IPTW method to raw numbers and is different from the actual participants included in the reporting arm.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban: Balanced Cohort | Incidence Rate Per 1000 Participant-Years For First Occurrence of Major Intracranial Bleeding Event After Index Date: Balanced Cohorts | 14.490 Events Per 1000 Participant-Years |
| Warfarin: Balanced Cohort | Incidence Rate Per 1000 Participant-Years For First Occurrence of Major Intracranial Bleeding Event After Index Date: Balanced Cohorts | 17.507 Events Per 1000 Participant-Years |
p-value: <0.00195% CI: [0.7, 0.84]COX Proportional Hazards Regression
Secondary
Incidence Rate Per 1000 Participant-Years For First Occurrence of Systemic Embolism (SE) Event After Index Date: Balanced Cohorts
Incidence rate per 1000 participant-years for the first occurrence of SE event after index date was reported. SE after index date not including the index date was identified using hospital claims which had a SE diagnosis code as the first listed ICD-10 diagnosis code. Index date: date when participants initiated warfarin or apixaban. Follow-up period: from next day of the index date till occurrence of target outcome event, discontinuation of apixaban or warfarin; switching from apixaban or warfarin; withdrawal from the database, whichever occurred first.
Time frame: Follow-up period during data observation period from Mar 2011 to Jun 2021 (approximately 10 years 4 months); extracted data evaluated in approximately 1 month of this study
Population: Eligible participants registered on MDV database, whose data was observed in the study. Analysis performed using IPTW method to balance participant characteristics among reporting groups. Here, Overall Number of Participants Analyzed is the number of participants after application of IPTW method to raw numbers and is different from the actual participants included in the reporting arm.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban: Balanced Cohort | Incidence Rate Per 1000 Participant-Years For First Occurrence of Systemic Embolism (SE) Event After Index Date: Balanced Cohorts | 5.285 Events Per 1000 Participant-Years |
| Warfarin: Balanced Cohort | Incidence Rate Per 1000 Participant-Years For First Occurrence of Systemic Embolism (SE) Event After Index Date: Balanced Cohorts | 18.923 Events Per 1000 Participant-Years |
p-value: <0.00195% CI: [0.229, 0.294]COX Proportional Hazards Regression