Atrial Fibrillation
Conditions
Brief summary
The objective is to assess the safety and effectiveness of new dabigatran and warfarin patients diagnosed with NVAF in the US DoD population.
Detailed description
Study Design: Retrospective
Interventions
None listed
Sponsors
Boehringer Ingelheim
Study design
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients must be continuously enrolled in a health plan during the pre-index period; * Patients must have at least one inpatient, or one physician office visit, emergency room visit with a diagnosis of AF (ICD-9-CM diagnosis code: 427.31in any position) on the index date or during the pre-index period; * Patients must have a prescription for dabigatran or warfarin (this first prescription will be the index date); * Patients must be treatment naive from all OAC use prior to first dabigatran or warfarin prescription; * Aged 18-89 on the index date;
Exclusion criteria
* Patients with valvular procedures related to the baseline AF diagnosis will be excluded; * Patients with transient causes of AF such as hyperthyroidism, any cardiac surgery, pericarditis, mycoarditis, pulmonary embolism within 3 months prior to their first diagnosis of AF;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Stroke (Hemorrhagic, Ischemic) | From October 1, 2009 through July 31, 2013 (the study period) | Event rate of stroke (hemorrhagic, ischemic). Variables in the final propensity score model: age, gender index year, baseline CHADS(2) score (Congestive heart failure, Hypertension, Age ≥75 years, Diabetes mellitus, Prior Stroke or transient ischemic attack (TIA) or Thromboembolism), baseline CHA(2)DS(2)-VASc score (Congestive heart failure, Hypertension, Age ≥75 years (doubled), Diabetes mellitus, Stroke (doubled), Vascular disease, Age 65-74 years, Sex category), baseline HAS-BLED score (Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile International Normalized Ratio, Elderly, Drugs/alcohol concomitantly), baseline use of several medications and presence of several baseline co-morbidities. The 12-month period prior to and including the index date was defined as the baseline period. Patients were required to have an NVAF diagnosis during this baseline period. |
| Major Bleeding | From October 1, 2009 through July 31, 2013 (the study period) | Event rate of major bleeding. The 12-month period prior to and including the index date was defined as the baseline period. Patients were required to have an NVAF diagnosis during this baseline period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Major Intracranial Bleeding | From October 1, 2009 through July 31, 2013 (the study period). | Event rate of major intracranial bleeding. The 12-month period prior to and including the index date was defined as the baseline period. Patients were required to have an NVAF diagnosis during this baseline period. |
| Major Extracranial Bleeding | From October 1, 2009 through July 31, 2013 (the study period). | Event rate of major extracranial bleeding. The 12-month period prior to and including the index date was defined as the baseline period. Patients were required to have an NVAF diagnosis during this baseline period. |
| Major GI Bleeding | From October 1, 2009 through July 31, 2013 (the study period). | Event rate of major gastrointestinal (GI) bleeding. The 12-month period prior to and including the index date was defined as the baseline period. Patients were required to have an NVAF diagnosis during this baseline period. |
| Major Upper GI Bleeding | From October 1, 2009 through July 31, 2013 (the study period). | Event rate of major upper gastrointestinal (GI) bleeding. The 12-month period prior to and including the index date was defined as the baseline period. Patients were required to have an NVAF diagnosis during this baseline period. |
| Major Lower GI Bleeding | From October 1, 2009 through July 31, 2013 (the study period). | Event rate of major lower gastrointestinal (GI) bleeding. The 12-month period prior to and including the index date was defined as the baseline period. Patients were required to have an NVAF diagnosis during this baseline period. |
| Major Urogenital Bleeding | From October 1, 2009 through July 31, 2013 (the study period). | Event rate of major urogenital bleeding. The 12-month period prior to and including the index date was defined as the baseline period. Patients were required to have an NVAF diagnosis during this baseline period. |
| Ischemic Stroke | From October 1, 2009 through July 31, 2013 (the study period) | Event rate of ischemic stroke. The 12-month period prior to and including the index date was defined as the baseline period. Patients were required to have an NVAF diagnosis during this baseline period. |
| Transient Ischemic Attack | From October 1, 2009 through July 31, 2013 (the study period). | Event rate of transient ischemic attacks. The 12-month period prior to and including the index date was defined as the baseline period. Patients were required to have an NVAF diagnosis during this baseline period. |
| Myocardial Infarction | From October 1, 2009 through July 31, 2013 (the study period). | Event rate of myocardial infarction. The 12-month period prior to and including the index date was defined as the baseline period. Patients were required to have an NVAF diagnosis during this baseline period. |
| Venous Thromboembolism | From October 1, 2009 through July 31, 2013 (the study period). | Event rate of venous thromboembolism. The 12-month period prior to and including the index date was defined as the baseline period. Patients were required to have an NVAF diagnosis during this baseline period. |
| Deep Vein Thrombosis | From October 1, 2009 through July 31, 2013 (the study period). | Event rate of deep vein thrombosis. The 12-month period prior to and including the index date was defined as the baseline period. Patients were required to have an NVAF diagnosis during this baseline period. |
| Pulmonary Embolism | From October 1, 2009 through July 31, 2013 (the study period). | Event rate of pulmonary embolism. The 12-month period prior to and including the index date was defined as the baseline period. Patients were required to have an NVAF diagnosis during this baseline period. |
| Death | From October 1, 2009 through July 31, 2013 (the study period). | Event rate of death, due to any cause. The 12-month period prior to and including the index date was defined as the baseline period. Patients were required to have an NVAF diagnosis during this baseline period. |
| Major Other Bleeding | From October 1, 2009 through July 31, 2013 (the study period). | Event rate of major other bleeding. The 12-month period prior to and including the index date was defined as the baseline period. Patients were required to have an NVAF diagnosis during this baseline period. |
| Hemorrhagic Stroke | From October 1, 2009 through July 31, 2013 (the study period). | Event rate of hemorrhagic stroke. The 12-month period prior to and including the index date was defined as the baseline period. Patients were required to have an NVAF diagnosis during this baseline period. |
Countries
United States
Participant flow
Recruitment details
Existing data cohort design with propensity score matching (PSM). Variables included in the final propensity score model were: age, gender index year, baseline CHADS(2) score, baseline CHA(2)DS(2)-VASc score, baseline HAS-BLED score, baseline use of several medications and presence of several baseline co-morbidities.
Participants by arm
| Arm | Count |
|---|---|
| Dabigatran Oral anticoagulant treatment-naive non-valvular atrial fibrillation (NVAF) patients aged 18-89 with their first prescription claim for dabigatran (either FDA-approved dose) during the study identification period (1 October 2010 and 31 July 2012). | 12,793 |
| Warfarin Oral anticoagulant treatment-naive non-valvular atrial fibrillation (NVAF) patients aged 18-89 with their first prescription claim for warfarin during the study identification period (1 October 2010 and 31 July 2012). | 12,793 |
| Total | 25,586 |
Baseline characteristics
| Characteristic | Dabigatran | Warfarin | Total |
|---|---|---|---|
| Age, Continuous | 73.8 years STANDARD_DEVIATION 9.3 | 74.0 years STANDARD_DEVIATION 9 | 73.9 years STANDARD_DEVIATION 9.2 |
| Sex: Female, Male Female | 5277 Participants | 5253 Participants | 10530 Participants |
| Sex: Female, Male Male | 7516 Participants | 7540 Participants | 15056 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
Major Bleeding
Event rate of major bleeding. The 12-month period prior to and including the index date was defined as the baseline period. Patients were required to have an NVAF diagnosis during this baseline period.
Time frame: From October 1, 2009 through July 31, 2013 (the study period)
Population: All patients in the post-propensity score matching cohort
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dabigatran | Major Bleeding | 30.84 Events per 1000 person-years |
| Warfarin | Major Bleeding | 37.04 Events per 1000 person-years |
95% CI: [0.71, 0.98]
Primary
Stroke (Hemorrhagic, Ischemic)
Event rate of stroke (hemorrhagic, ischemic). Variables in the final propensity score model: age, gender index year, baseline CHADS(2) score (Congestive heart failure, Hypertension, Age ≥75 years, Diabetes mellitus, Prior Stroke or transient ischemic attack (TIA) or Thromboembolism), baseline CHA(2)DS(2)-VASc score (Congestive heart failure, Hypertension, Age ≥75 years (doubled), Diabetes mellitus, Stroke (doubled), Vascular disease, Age 65-74 years, Sex category), baseline HAS-BLED score (Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile International Normalized Ratio, Elderly, Drugs/alcohol concomitantly), baseline use of several medications and presence of several baseline co-morbidities. The 12-month period prior to and including the index date was defined as the baseline period. Patients were required to have an NVAF diagnosis during this baseline period.
Time frame: From October 1, 2009 through July 31, 2013 (the study period)
Population: All patients in the post-propensity score matching cohort
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dabigatran | Stroke (Hemorrhagic, Ischemic) | 9.15 Events per 1000 person-years |
| Warfarin | Stroke (Hemorrhagic, Ischemic) | 13.19 Events per 1000 person-years |
95% CI: [0.52, 0.92]
Secondary
Death
Event rate of death, due to any cause. The 12-month period prior to and including the index date was defined as the baseline period. Patients were required to have an NVAF diagnosis during this baseline period.
Time frame: From October 1, 2009 through July 31, 2013 (the study period).
Population: All patients in the post-propensity score matching cohort
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dabigatran | Death | 31.28 Events per 1000 person-years |
| Warfarin | Death | 52.41 Events per 1000 person-years |
95% CI: [0.52, 0.69]
Secondary
Deep Vein Thrombosis
Event rate of deep vein thrombosis. The 12-month period prior to and including the index date was defined as the baseline period. Patients were required to have an NVAF diagnosis during this baseline period.
Time frame: From October 1, 2009 through July 31, 2013 (the study period).
Population: All patients in the post-propensity score matching cohort
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dabigatran | Deep Vein Thrombosis | 0.58 Events per 1000 person-years |
| Warfarin | Deep Vein Thrombosis | 1.31 Events per 1000 person-years |
95% CI: [0.16, 1.21]
Secondary
Hemorrhagic Stroke
Event rate of hemorrhagic stroke. The 12-month period prior to and including the index date was defined as the baseline period. Patients were required to have an NVAF diagnosis during this baseline period.
Time frame: From October 1, 2009 through July 31, 2013 (the study period).
Population: All patients in the post-propensity score matching cohort
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dabigatran | Hemorrhagic Stroke | 0.77 Events per 1000 person-years |
| Warfarin | Hemorrhagic Stroke | 2.50 Events per 1000 person-years |
95% CI: [0.13, 0.7]
Secondary
Ischemic Stroke
Event rate of ischemic stroke. The 12-month period prior to and including the index date was defined as the baseline period. Patients were required to have an NVAF diagnosis during this baseline period.
Time frame: From October 1, 2009 through July 31, 2013 (the study period)
Population: All patients in the post-propensity score matching cohort
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dabigatran | Ischemic Stroke | 8.48 Events per 1000 person-years |
| Warfarin | Ischemic Stroke | 10.69 Events per 1000 person-years |
95% CI: [0.59, 1.07]
Secondary
Major Extracranial Bleeding
Event rate of major extracranial bleeding. The 12-month period prior to and including the index date was defined as the baseline period. Patients were required to have an NVAF diagnosis during this baseline period.
Time frame: From October 1, 2009 through July 31, 2013 (the study period).
Population: All patients in the post-propensity score matching cohort
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dabigatran | Major Extracranial Bleeding | 28.13 Events per 1000 person-years |
| Warfarin | Major Extracranial Bleeding | 31.30 Events per 1000 person-years |
95% CI: [0.76, 1.07]
Secondary
Major GI Bleeding
Event rate of major gastrointestinal (GI) bleeding. The 12-month period prior to and including the index date was defined as the baseline period. Patients were required to have an NVAF diagnosis during this baseline period.
Time frame: From October 1, 2009 through July 31, 2013 (the study period).
Population: All patients in the post-propensity score matching cohort
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dabigatran | Major GI Bleeding | 25.40 Events per 1000 person-years |
| Warfarin | Major GI Bleeding | 23.69 Events per 1000 person-years |
95% CI: [0.89, 1.3]
Secondary
Major Intracranial Bleeding
Event rate of major intracranial bleeding. The 12-month period prior to and including the index date was defined as the baseline period. Patients were required to have an NVAF diagnosis during this baseline period.
Time frame: From October 1, 2009 through July 31, 2013 (the study period).
Population: All patients in the post-propensity score matching cohort
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dabigatran | Major Intracranial Bleeding | 2.69 Events per 1000 person-years |
| Warfarin | Major Intracranial Bleeding | 5.65 Events per 1000 person-years |
95% CI: [0.3, 0.77]
Secondary
Major Lower GI Bleeding
Event rate of major lower gastrointestinal (GI) bleeding. The 12-month period prior to and including the index date was defined as the baseline period. Patients were required to have an NVAF diagnosis during this baseline period.
Time frame: From October 1, 2009 through July 31, 2013 (the study period).
Population: All patients in the post-propensity score matching cohort
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dabigatran | Major Lower GI Bleeding | 20.25 Events per 1000 person-years |
| Warfarin | Major Lower GI Bleeding | 16.38 Events per 1000 person-years |
95% CI: [0.99, 1.54]
Secondary
Major Other Bleeding
Event rate of major other bleeding. The 12-month period prior to and including the index date was defined as the baseline period. Patients were required to have an NVAF diagnosis during this baseline period.
Time frame: From October 1, 2009 through July 31, 2013 (the study period).
Population: All patients in the post-propensity score matching cohort
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dabigatran | Major Other Bleeding | 1.92 Events per 1000 person-years |
| Warfarin | Major Other Bleeding | 5.13 Events per 1000 person-years |
95% CI: [0.22, 0.64]
Secondary
Major Upper GI Bleeding
Event rate of major upper gastrointestinal (GI) bleeding. The 12-month period prior to and including the index date was defined as the baseline period. Patients were required to have an NVAF diagnosis during this baseline period.
Time frame: From October 1, 2009 through July 31, 2013 (the study period).
Population: All patients in the post-propensity score matching cohort
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dabigatran | Major Upper GI Bleeding | 5.48 Events per 1000 person-years |
| Warfarin | Major Upper GI Bleeding | 7.63 Events per 1000 person-years |
95% CI: [0.5, 1.03]
Secondary
Major Urogenital Bleeding
Event rate of major urogenital bleeding. The 12-month period prior to and including the index date was defined as the baseline period. Patients were required to have an NVAF diagnosis during this baseline period.
Time frame: From October 1, 2009 through July 31, 2013 (the study period).
Population: All patients in the post-propensity score matching cohort
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dabigatran | Major Urogenital Bleeding | 1.06 Events per 1000 person-years |
| Warfarin | Major Urogenital Bleeding | 3.02 Events per 1000 person-years |
95% CI: [0.17, 0.72]
Secondary
Myocardial Infarction
Event rate of myocardial infarction. The 12-month period prior to and including the index date was defined as the baseline period. Patients were required to have an NVAF diagnosis during this baseline period.
Time frame: From October 1, 2009 through July 31, 2013 (the study period).
Population: All patients in the post-propensity score matching cohort
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dabigatran | Myocardial Infarction | 5.09 Events per 1000 person-years |
| Warfarin | Myocardial Infarction | 7.77 Events per 1000 person-years |
95% CI: [0.45, 0.95]
Secondary
Pulmonary Embolism
Event rate of pulmonary embolism. The 12-month period prior to and including the index date was defined as the baseline period. Patients were required to have an NVAF diagnosis during this baseline period.
Time frame: From October 1, 2009 through July 31, 2013 (the study period).
Population: All patients in the post-propensity score matching cohort
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dabigatran | Pulmonary Embolism | 0.77 Events per 1000 person-years |
| Warfarin | Pulmonary Embolism | 0.79 Events per 1000 person-years |
95% CI: [0.34, 2.81]
Secondary
Transient Ischemic Attack
Event rate of transient ischemic attacks. The 12-month period prior to and including the index date was defined as the baseline period. Patients were required to have an NVAF diagnosis during this baseline period.
Time frame: From October 1, 2009 through July 31, 2013 (the study period).
Population: All patients in the post-propensity score matching cohort
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dabigatran | Transient Ischemic Attack | 4.62 Events per 1000 person-years |
| Warfarin | Transient Ischemic Attack | 5.53 Events per 1000 person-years |
95% CI: [0.55, 1.26]
Secondary
Venous Thromboembolism
Event rate of venous thromboembolism. The 12-month period prior to and including the index date was defined as the baseline period. Patients were required to have an NVAF diagnosis during this baseline period.
Time frame: From October 1, 2009 through July 31, 2013 (the study period).
Population: All patients in the post-propensity score matching cohort
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dabigatran | Venous Thromboembolism | 1.34 Events per 1000 person-years |
| Warfarin | Venous Thromboembolism | 2.10 Events per 1000 person-years |
95% CI: [0.31, 1.31]