Atrial Fibrillation
Conditions
Brief summary
Investigators are building an empirical evidence base for real world data through large-scale replication of randomized controlled trials. The investigators' goal is to understand for what types of clinical questions real world data analyses can be conducted with confidence and how to implement such studies.
Detailed description
This is a non-randomized, non-interventional study that is part of the RCT DUPLICATE initiative (www.rctduplicate.org) of the Brigham and Women's Hospital, Harvard Medical School. It is intended to replicate, as closely as possible in healthcare insurance claims data, the trial listed below/above. Although many features of the trial cannot be directly replicated in healthcare claims, key design features, including outcomes, exposures, and inclusion/exclusion criteria, were selected to proxy those features from the trial. Randomization is also not replicable in healthcare claims data but was proxied through a statistical balancing of measured covariates through standard practice. Investigators assume that the RCT provides the reference standard treatment effect estimate and that failure to replicate RCT findings is indicative of the inadequacy of the healthcare claims data for replication for a range of possible reasons and does not provide information on the validity of the original RCT finding.
Interventions
DRUGRivaroxaban
Any rivaroxaban dispensing claim is used as the reference group
DRUGApixaban
Any apixaban dispensing claim is used as the exposure group
Sponsors
Brigham and Women's Hospital
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
* At least 18 years of age * Non-valvular atrial fibrillation
Exclusion criteria
* Prior anticoagulant use \[Day -180, Day 0\] * Stage 4 or 5 chronic kidney disease or end-stage renal disease \[Day -180, Day 0\] * Dialysis or renal transplant \[Day -180, Day 0\] * Recent major or clinically relevant non-major bleeding \[Day -180, Day 0\] * Other indications for anticoagulation (DVT, PE, or prosthetic heart valve) \[Day -180, Day 0\] * Use of an antiplatelet \[Day -180, Day 0\] * Significant liver disease and coagulopathy \[Day -180, Day 0\] * Use of CYP3A4 or P-gp inhibitors or inducers \[Day -180, Day 0\] * Pregnancy or breastfeeding \[Day -180, Day 0\] * Cancer \[Day -180, Day 0\] * Bypass surgery, obesity, or the use of a weight loss or appetite suppressor \[Day -180, Day 0\] * Mitral stenosis with or without insufficiency, mitral rheumatic insufficiency, and other/unspecified mitral valve disorders \[Day -180, Day 0\]
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Major Bleeding or Clinically Relevant Non-major Bleeding Events | Through study completion or censoring, up to 365 days | Claims-based algorithm: incidence of major bleeding or clinically relevant non-major bleeding events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Clinically Relevant Non-major Bleeding | Through study completion or censoring, up to 365 days | Claims-based algorithm: Incidence of clinically relevant non-major bleeding |
| Incidence of All-cause Mortality | Through study completion or censoring, up to 365 days | Claims-based algorithm: Incidence of all-cause mortality |
| Incidence of Major Bleeding | Through study completion or censoring, up to 365 days | Claims-based algorithm: Incidence of major bleeding |
| Incidence of Extracranial Bleeding | Through study completion or censoring, up to 365 days | Claims-based algorithm: Incidence of extracranial bleeding (any position) |
| Incidence of Intracranial Bleeding | Through study completion or censoring, up to 365 days | Claims-based algorithm: Incidence of intracranial bleeding (any position) |
| Incidence of Stroke | Through study completion or censoring, up to 365 days | Claims-based algorithm: Incidence of stroke |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Rivaroxaban Reference group
Rivaroxaban: Any rivaroxaban dispensing claim is used as the reference group | 176 |
| Apixaban Exposure group
Apixaban: Any apixaban dispensing claim is used as the exposure group | 176 |
| Total | 352 |
Baseline characteristics
| Characteristic | Rivaroxaban | Apixaban | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 150,714 Participants | 150,659 Participants | 301373 Participants |
| Age, Categorical Between 18 and 65 years | 26,276 Participants | 26,331 Participants | 52607 Participants |
| Age, Continuous | 73.91 years STANDARD_DEVIATION 9.65 | 73.88 years STANDARD_DEVIATION 9.75 | 73.90 years STANDARD_DEVIATION 9.7 |
| Race/Ethnicity, Customized Asian | 2,554 Participants | 2,554 Participants | 5108 Participants |
| Race/Ethnicity, Customized Black | 7,016 Participants | 7,011 Participants | 14027 Participants |
| Race/Ethnicity, Customized Hispanic | 4,140 Participants | 4,162 Participants | 8302 Participants |
| Race/Ethnicity, Customized N/A | 30,904 Participants | 30,907 Participants | 61811 Participants |
| Race/Ethnicity, Customized North American Native | 326 Participants | 332 Participants | 658 Participants |
| Race/Ethnicity, Customized Other | 1,283 Participants | 1,283 Participants | 2566 Participants |
| Race/Ethnicity, Customized Unknown/Missing | 2,830 Participants | 2,792 Participants | 5622 Participants |
| Race/Ethnicity, Customized White | 127,937 Participants | 127,949 Participants | 255886 Participants |
| Region of Enrollment United States | 176,990 participants | 176,990 participants | 353980 participants |
| Sex: Female, Male Female | 88,058 Participants | 88,018 Participants | 176076 Participants |
| Sex: Female, Male Male | 88,932 Participants | 88,972 Participants | 177904 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1,958 / 176,990 | 1,840 / 176,990 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
Incidence of Major Bleeding or Clinically Relevant Non-major Bleeding Events
Claims-based algorithm: incidence of major bleeding or clinically relevant non-major bleeding events
Time frame: Through study completion or censoring, up to 365 days
Population: Propensity score matched population across 3 databases
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rivaroxaban | Incidence of Major Bleeding or Clinically Relevant Non-major Bleeding Events | 9.2 No. of new events per 100 person-years |
| Apixaban | Incidence of Major Bleeding or Clinically Relevant Non-major Bleeding Events | 6.4 No. of new events per 100 person-years |
Comparison: Hazard ratio95% CI: [0.66, 0.71]
Secondary
Incidence of All-cause Mortality
Claims-based algorithm: Incidence of all-cause mortality
Time frame: Through study completion or censoring, up to 365 days
Population: Propensity score matched population across 3 databases
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rivaroxaban | Incidence of All-cause Mortality | 2.7 No. of new events per 100 person-years |
| Apixaban | Incidence of All-cause Mortality | 2.4 No. of new events per 100 person-years |
Secondary
Incidence of Clinically Relevant Non-major Bleeding
Claims-based algorithm: Incidence of clinically relevant non-major bleeding
Time frame: Through study completion or censoring, up to 365 days
Population: Propensity score matched population across 3 databases
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rivaroxaban | Incidence of Clinically Relevant Non-major Bleeding | 8.7 No. of new events per 100 person-years |
| Apixaban | Incidence of Clinically Relevant Non-major Bleeding | 5.9 No. of new events per 100 person-years |
Secondary
Incidence of Extracranial Bleeding
Claims-based algorithm: Incidence of extracranial bleeding (any position)
Time frame: Through study completion or censoring, up to 365 days
Population: Propensity score matched population across 3 databases
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rivaroxaban | Incidence of Extracranial Bleeding | 3.6 No. of new events per 100 person-years |
| Apixaban | Incidence of Extracranial Bleeding | 2.1 No. of new events per 100 person-years |
Secondary
Incidence of Intracranial Bleeding
Claims-based algorithm: Incidence of intracranial bleeding (any position)
Time frame: Through study completion or censoring, up to 365 days
Population: Propensity score matched. population across 3 databases
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rivaroxaban | Incidence of Intracranial Bleeding | 0.4 No. of new events per 100 person-years |
| Apixaban | Incidence of Intracranial Bleeding | 0.3 No. of new events per 100 person-years |
Secondary
Incidence of Major Bleeding
Claims-based algorithm: Incidence of major bleeding
Time frame: Through study completion or censoring, up to 365 days
Population: Propensity score matched population across 3 databases
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rivaroxaban | Incidence of Major Bleeding | 4.0 No. of new events per 100 person-years |
| Apixaban | Incidence of Major Bleeding | 2.4 No. of new events per 100 person-years |
Secondary
Incidence of Stroke
Claims-based algorithm: Incidence of stroke
Time frame: Through study completion or censoring, up to 365 days
Population: Propensity score matched population across 3 databases
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rivaroxaban | Incidence of Stroke | 1.1 No. of new events per 100 person-years |
| Apixaban | Incidence of Stroke | 0.9 No. of new events per 100 person-years |