Non-valvular Atrial Fibrillation
Conditions
Keywords
Stroke, Apixaban, Warfarin
Brief summary
The objective of this study is to investigate safety and effectiveness of apixaban compared to warfarin in very elderly patients with Non-valvular atrial fibrillation (NVAF). In addition to the absolute age, effects on higher age-related risk factors on relative risk of apixaban to warfarin is also investigated through subgroup analyses.
Detailed description
This is a retrospective non-intervention observational study to evaluate the difference in safety and effectiveness between apixaban and warfarin using a database provided by Medical Data Vision Co. Ltd. (MDV Co. Ltd.). Eligible patients will be extracted from the database and allocated to the pre-defined cohorts based on the actual age, age of NVAF diagnosis and types of anticoagulant therapy. Patient characteristics will be balanced by an Inverse probability of treatment weighting (IPTW) method, and risk of stroke/SE (primary effectiveness endpoint) and major bleeding (primary safety endpoint) will be compared.
Interventions
DRUGApixaban
This is observational study and the patients in the apixaban cohort include those who are exposed to apixaban in the real world settings.
DRUGWarfarin
This is observational study and the patients in the warfarin cohort include those who are exposed to warfarin in the real world settings.
Sponsors
Pfizer
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
80 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients must meet all the following inclusion criteria to be eligible for inclusion in the study. 1. 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. 2. 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 3. No use of the any Oral anticoagulants (OAC)s during the baseline period (the 180 days before the index date) 4. Age of 18 years or older on the index date. 5. Index date is at age 80 or older
Exclusion criteria
* Patients meeting any of the following criteria will not be included in the study: 1. 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 2. Having a cardiac surgery procedure record during the baseline period 3. Having a joint replacement procedure record during the baseline period 4. Having a procedure of prosthetic heart valve during the baseline period 5. Having a diagnosis of venous thromboembolism during the baseline period 6. Female patients with pregnancy during the follow-up period 7. Patients prescribed off-label doses of OACs (per Japanese package insert of each OAC) or patients treated with OAC but in off-label or contraindicated manners.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence Rate (Per 1,000 Participant-Year) of Composite of Stroke and Systemic Embolism (SE): Balanced Cohorts | Follow-up period during data observation period from 26-Feb-2013 to 31-Dec-2021 (approximately 8 years 10 months); extracted data evaluated in approximately 3.5 months 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 ischemic and hemorrhagic stroke. International Classification of Diseases 10th Revision (ICD-10) diagnosis code was used to label the events. Index date was defined as a date when participants initiated warfarin or apixaban. Follow-up period: the next day of the index date till occurrence of target outcome, discontinuation of the warfarin or apixaban, switching from the warfarin or apixaban, withdrawal from the database, whichever observed first. |
| Incidence Rate (Per 1,000 Participant-Year) of Major Bleeding: Balanced Cohorts | Follow-up period during data observation period from 26-Feb-2013 to 31-Dec-2021 (approximately 8 years 10 months); extracted data evaluated in approximately 3.5 months 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. ICD-10 diagnosis code was used to label the events. Index date was defined as a date when participants initiated warfarin or apixaban. Follow-up period: the next day of the index date till occurrence of target outcome, discontinuation of the warfarin or apixaban, switching from the warfarin or apixaban, withdrawal from the database, whichever observed first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence Rate (Per 1,000 Participant-Year) of Intracranial Hemorrhage: Balanced Cohorts | Follow-up period during data observation period from 26-Feb-2013 to 31-Dec-2021 (approximately 8 years 10 months); extracted data evaluated in approximately 3.5 months of this study | Incidence rate per 1000 participant-years for the first occurrence of intracranial hemorrhage event after index date was reported. ICD-10 diagnosis code was used to label the events. Index date was defined as a date when participants initiated warfarin or apixaban. Follow-up period: the next day of the index date till occurrence of target outcome, discontinuation of the warfarin or apixaban, switching from warfarin or apixaban, withdrawal from the database, whichever observed first. |
| Incidence Rate (Per 1,000 Participant-Year) of Cardiogenic Cerebral Embolism: Balanced Cohorts | Follow-up period during data observation period from 26-Feb-2013 to 31-Dec-2021 (approximately 8 years 10 months); extracted data evaluated in approximately 3.5 months of this study | Incidence rate per 1000 participant-years for the first occurrence of cardiogenic cerebral embolism events after index date was reported. ICD-10 diagnosis code was used to label the events. Index date was defined as a date when participants initiated warfarin or apixaban. Follow-up period: the next day of the index date till occurrence of target outcome, discontinuation of the warfarin or apixaban, switching from warfarin or apixaban, withdrawal from the database, whichever observed first. |
| Incidence Rate (Per 1,000 Participant-Year) of Intraocular Bleeding: Balanced Cohorts | Follow-up period during data observation period from 26-Feb-2013 to 31-Dec-2021 (approximately 8 years 10 months); extracted data evaluated in approximately 3.5 months of this study | Incidence rate per 1000 participant-years for the first occurrence of intraocular bleeding event after index date was reported. ICD-10 diagnosis code was used to label the events. Index date was defined as a date when participants initiated warfarin or apixaban. Follow-up period: the next day of the index date till occurrence of target outcome, discontinuation of the warfarin or apixaban, switching from warfarin or apixaban, withdrawal from the database, whichever observed first. |
| Incidence Rate (Per 1,000 Participant-Year) of Gastrointestinal Bleeding: Balanced Cohorts | Follow-up period during data observation period from 26-Feb-2013 to 31-Dec-2021 (approximately 8 years 10 months); extracted data evaluated in approximately 3.5 months of this study | Incidence rate per 1000 participant-years for the first occurrence of major GI bleeding event after index date was reported. ICD-10 diagnosis code was used to label the events. Index date was defined as a date when participants initiated warfarin or apixaban. Follow-up period: the next day of the index date till occurrence of target outcome, discontinuation of the warfarin or apixaban, switching from warfarin or apixaban, withdrawal from the database, whichever observed first. |
| Incidence Rate (Per 1,000 Participant-Year) of Ischemic Stroke (Cerebral Infarction): Balanced Cohorts | Follow-up period during data observation period from 26-Feb-2013 to 31-Dec-2021 (approximately 8 years 10 months); extracted data evaluated in approximately 3.5 months of this study | Incidence rate per 1000 participant-years for the first occurrence of ischemic stroke event after index date was reported. ICD-10 diagnosis code was used to label the events. Index date was defined as a date when participants initiated warfarin or apixaban. Follow-up period: the next day of the index date till occurrence of target outcome, discontinuation of the warfarin or apixaban, switching from warfarin or apixaban, withdrawal from the database, whichever observed first. |
Countries
Japan
Participant flow
Recruitment details
Data of participants who received apixaban or warfarin (80 years or older) after getting diagnosed with non-valvular atrial fibrillation (NVAF) 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 26-Feb-2013 to 31-Dec-2021. Extracted data was evaluated for objectives of this study in approximately 3.5 months of this study.
Participants by arm
| Arm | Count |
|---|---|
| Warfarin Cohort Participants included in this cohort were those who received warfarin in real world practice after getting diagnosed with NVAF. Data of the participants included were retrieved from MDV database and was observed retrospectively in this study. | 39,936 |
| Apixaban Cohort Participants included in this cohort were those who received apixaban in real world practice after getting diagnosed with NVAF. Data of the participants included were retrieved from MDV database and was observed retrospectively in this study. | 37,878 |
| Total | 77,814 |
Baseline characteristics
| Characteristic | Warfarin Cohort | Apixaban Cohort | Total |
|---|---|---|---|
| Age, Continuous | 85.3 Years STANDARD_DEVIATION 4.15 | 85.7 Years STANDARD_DEVIATION 4.22 | 85.5 Years STANDARD_DEVIATION 4.19 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Sex: Female, Male Female | 18804 Participants | 19171 Participants | 37975 Participants |
| Sex: Female, Male Male | 21132 Participants | 18707 Participants | 39839 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 1,000 Participant-Year) of Composite of Stroke and Systemic Embolism (SE): 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 ischemic and hemorrhagic stroke. International Classification of Diseases 10th Revision (ICD-10) diagnosis code was used to label the events. Index date was defined as a date when participants initiated warfarin or apixaban. Follow-up period: the next day of the index date till occurrence of target outcome, discontinuation of the warfarin or apixaban, switching from the warfarin or apixaban, withdrawal from the database, whichever observed first.
Time frame: Follow-up period during data observation period from 26-Feb-2013 to 31-Dec-2021 (approximately 8 years 10 months); extracted data evaluated in approximately 3.5 months of this study
Population: Eligible participants registered on MDV database, whose data was observed in the study. Analysis was performed using inverse probability treatment weighting with stabilized weights (s-IPTW) method to balance participant characteristics among reporting groups. Here, Overall Number of Participants Analyzed is the number of participants after application of s-IPTW method to raw numbers and is different from the actual participants included in the reporting arm.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Warfarin: Balanced Cohort | Incidence Rate (Per 1,000 Participant-Year) of Composite of Stroke and Systemic Embolism (SE): Balanced Cohorts | 75.227 Events Per 1000 Participant-Years |
| Apixaban: Balanced Cohort | Incidence Rate (Per 1,000 Participant-Year) of Composite of Stroke and Systemic Embolism (SE): Balanced Cohorts | 55.801 Events Per 1000 Participant-Years |
p-value: <0.00195% CI: [0.711, 0.798]Log Rank
Primary
Incidence Rate (Per 1,000 Participant-Year) of Major Bleeding: 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. ICD-10 diagnosis code was used to label the events. Index date was defined as a date when participants initiated warfarin or apixaban. Follow-up period: the next day of the index date till occurrence of target outcome, discontinuation of the warfarin or apixaban, switching from the warfarin or apixaban, withdrawal from the database, whichever observed first.
Time frame: Follow-up period during data observation period from 26-Feb-2013 to 31-Dec-2021 (approximately 8 years 10 months); extracted data evaluated in approximately 3.5 months of this study
Population: Eligible participants registered on MDV database, whose data was observed in the study. Analysis was performed using s-IPTW method to balance participant characteristics among reporting groups. Here, Overall Number of Participants Analyzed is the number of participants after application of s-IPTW method to raw numbers and is different from the actual participants included in the reporting arm.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Warfarin: Balanced Cohort | Incidence Rate (Per 1,000 Participant-Year) of Major Bleeding: Balanced Cohorts | 25.328 Events Per 1000 Participant-Years |
| Apixaban: Balanced Cohort | Incidence Rate (Per 1,000 Participant-Year) of Major Bleeding: Balanced Cohorts | 17.306 Events Per 1000 Participant-Years |
p-value: <0.00195% CI: [0.622, 0.76]Log Rank
Secondary
Incidence Rate (Per 1,000 Participant-Year) of Cardiogenic Cerebral Embolism: Balanced Cohorts
Incidence rate per 1000 participant-years for the first occurrence of cardiogenic cerebral embolism events after index date was reported. ICD-10 diagnosis code was used to label the events. Index date was defined as a date when participants initiated warfarin or apixaban. Follow-up period: the next day of the index date till occurrence of target outcome, discontinuation of the warfarin or apixaban, switching from warfarin or apixaban, withdrawal from the database, whichever observed first.
Time frame: Follow-up period during data observation period from 26-Feb-2013 to 31-Dec-2021 (approximately 8 years 10 months); extracted data evaluated in approximately 3.5 months of this study
Population: Eligible participants registered on MDV database, whose data was observed in the study. Analysis was performed using s-IPTW method to balance participant characteristics among reporting groups. Here, Overall Number of Participants Analyzed is the number of participants after application of s-IPTW method to raw numbers and is different from the actual participants included in the reporting arm.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Warfarin: Balanced Cohort | Incidence Rate (Per 1,000 Participant-Year) of Cardiogenic Cerebral Embolism: Balanced Cohorts | 21.386 Events Per 1000 Participant-Years |
| Apixaban: Balanced Cohort | Incidence Rate (Per 1,000 Participant-Year) of Cardiogenic Cerebral Embolism: Balanced Cohorts | 13.473 Events Per 1000 Participant-Years |
p-value: <0.00195% CI: [0.57, 0.714]Log Rank
Secondary
Incidence Rate (Per 1,000 Participant-Year) of Gastrointestinal Bleeding: Balanced Cohorts
Incidence rate per 1000 participant-years for the first occurrence of major GI bleeding event after index date was reported. ICD-10 diagnosis code was used to label the events. Index date was defined as a date when participants initiated warfarin or apixaban. Follow-up period: the next day of the index date till occurrence of target outcome, discontinuation of the warfarin or apixaban, switching from warfarin or apixaban, withdrawal from the database, whichever observed first.
Time frame: Follow-up period during data observation period from 26-Feb-2013 to 31-Dec-2021 (approximately 8 years 10 months); extracted data evaluated in approximately 3.5 months of this study
Population: Eligible participants registered on MDV database, whose data was observed in the study. Analysis was performed using s-IPTW method to balance participant characteristics among reporting groups. Here, Overall Number of Participants Analyzed is the number of participants after application of s-IPTW method to raw numbers and is different from the actual participants included in the reporting arm.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Warfarin: Balanced Cohort | Incidence Rate (Per 1,000 Participant-Year) of Gastrointestinal Bleeding: Balanced Cohorts | 42.641 Events Per 1000 Participant-Years |
| Apixaban: Balanced Cohort | Incidence Rate (Per 1,000 Participant-Year) of Gastrointestinal Bleeding: Balanced Cohorts | 36.595 Events Per 1000 Participant-Years |
p-value: <0.00195% CI: [0.807, 0.934]Log Rank
Secondary
Incidence Rate (Per 1,000 Participant-Year) of Intracranial Hemorrhage: Balanced Cohorts
Incidence rate per 1000 participant-years for the first occurrence of intracranial hemorrhage event after index date was reported. ICD-10 diagnosis code was used to label the events. Index date was defined as a date when participants initiated warfarin or apixaban. Follow-up period: the next day of the index date till occurrence of target outcome, discontinuation of the warfarin or apixaban, switching from warfarin or apixaban, withdrawal from the database, whichever observed first.
Time frame: Follow-up period during data observation period from 26-Feb-2013 to 31-Dec-2021 (approximately 8 years 10 months); extracted data evaluated in approximately 3.5 months of this study
Population: Eligible participants registered on MDV database, whose data was observed in the study. Analysis was performed using s-IPTW method to balance participant characteristics among reporting groups. Here, Overall Number of Participants Analyzed is the number of participants after application of s-IPTW method to raw numbers and is different from the actual participants included in the reporting arm.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Warfarin: Balanced Cohort | Incidence Rate (Per 1,000 Participant-Year) of Intracranial Hemorrhage: Balanced Cohorts | 20.787 Events Per 1000 Participant-Years |
| Apixaban: Balanced Cohort | Incidence Rate (Per 1,000 Participant-Year) of Intracranial Hemorrhage: Balanced Cohorts | 13.138 Events Per 1000 Participant-Years |
p-value: <0.00195% CI: [0.57, 0.715]Log Rank
Secondary
Incidence Rate (Per 1,000 Participant-Year) of Intraocular Bleeding: Balanced Cohorts
Incidence rate per 1000 participant-years for the first occurrence of intraocular bleeding event after index date was reported. ICD-10 diagnosis code was used to label the events. Index date was defined as a date when participants initiated warfarin or apixaban. Follow-up period: the next day of the index date till occurrence of target outcome, discontinuation of the warfarin or apixaban, switching from warfarin or apixaban, withdrawal from the database, whichever observed first.
Time frame: Follow-up period during data observation period from 26-Feb-2013 to 31-Dec-2021 (approximately 8 years 10 months); extracted data evaluated in approximately 3.5 months of this study
Population: Eligible participants registered on MDV database, whose data was observed in the study. Analysis was performed using s-IPTW method to balance participant characteristics among reporting groups. Here, Overall Number of Participants Analyzed is the number of participants after application of s-IPTW method to raw numbers and is different from the actual participants included in the reporting arm.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Warfarin: Balanced Cohort | Incidence Rate (Per 1,000 Participant-Year) of Intraocular Bleeding: Balanced Cohorts | 4.224 Events Per 1000 Participant-Years |
| Apixaban: Balanced Cohort | Incidence Rate (Per 1,000 Participant-Year) of Intraocular Bleeding: Balanced Cohorts | 2.682 Events Per 1000 Participant-Years |
p-value: <0.00195% CI: [0.503, 0.83]Log Rank
Secondary
Incidence Rate (Per 1,000 Participant-Year) of Ischemic Stroke (Cerebral Infarction): Balanced Cohorts
Incidence rate per 1000 participant-years for the first occurrence of ischemic stroke event after index date was reported. ICD-10 diagnosis code was used to label the events. Index date was defined as a date when participants initiated warfarin or apixaban. Follow-up period: the next day of the index date till occurrence of target outcome, discontinuation of the warfarin or apixaban, switching from warfarin or apixaban, withdrawal from the database, whichever observed first.
Time frame: Follow-up period during data observation period from 26-Feb-2013 to 31-Dec-2021 (approximately 8 years 10 months); extracted data evaluated in approximately 3.5 months of this study
Population: Eligible participants registered on MDV database, whose data was observed in the study. Analysis was performed using s-IPTW method to balance participant characteristics among reporting groups. Here, Overall Number of Participants Analyzed is the number of participants after application of s-IPTW method to raw numbers and is different from the actual participants included in the reporting arm.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Warfarin: Balanced Cohort | Incidence Rate (Per 1,000 Participant-Year) of Ischemic Stroke (Cerebral Infarction): Balanced Cohorts | 39.607 Events Per 1000 Participant-Years |
| Apixaban: Balanced Cohort | Incidence Rate (Per 1,000 Participant-Year) of Ischemic Stroke (Cerebral Infarction): Balanced Cohorts | 33.279 Events Per 1000 Participant-Years |
p-value: <0.00195% CI: [0.791, 0.922]Log Rank