Atrial Fibrillation
Conditions
Brief summary
This cohort study is the sequential expansion of the comparative effectiveness study of oral anticoagulants and plans to identify initiators of oral anticoagulants using electronic claims data from a commercial insurance database to quantify associations between anticoagulant choice (warfarin and dabigatran) and the occurrence of selected outcomes in patients with non-valvular atrial fibrillation at risk for stroke.
Interventions
None listed
Sponsors
Boehringer Ingelheim
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* A recorded diagnosis of atrial fibrillation. * Initiation of anticoagulant medication (dabigatran (or other new oral anticoagulants as they become available) or warfarin). * At least 18 years of age on the date of anticoagulant initiation. * Congestive Heart Failure, Hypertension, Age \> 75, Diabetes Mellitus, Prior Stroke or Transient Ischemic Attack, Vascular Disease, Age 65-74, Sex Category (CHA2DS2-VASc) score at least 1
Exclusion criteria
* Patients with missing or ambiguous age or sex information. * Patients with evidence of valvular disease. * Patients with less than 12 months enrolment preceding the date of anticoagulant initiation * Patients with a dispensing of any oral anticoagulant during the 12 months preceding the date of anticoagulant initiation * Patients with a nursing home stay during the 12 months preceding the date of anticoagulant initiation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Stroke (Hemorrhagic, Ischemic, or Stroke of Uncertain Classification) | From October 2010 to September 2015 (the study period) | The rate of overall stroke (hemorrhagic, ischemic or stroke of uncertain classification ) in patients who are matched on propensity score and calendar quarter of initiation. Event rates were calculated as the total number of patients in each treatment group who had the outcome during follow-up divided by the total person-years at risk in the cohort. The outcome definition includes following: As primary International Classification of Diseases, Ninth Revision (ICD-9) discharge diagnosis (Dx): 431.x Intracerebral hemorrhage (ICH), 433.x1 Occlusion and stenosis of precerebral arteries with cerebral infarction, 434.x1 Occlusion and stenosis of cerebral arteries with cerebral infarction, 436.x Acute, but ill-defined cerebrovascular events. |
| Major Bleeding | From October 2010 to September 2015 (the study period) | The rate of major bleeding (Major intracranial bleeding and major extracranial bleed ) in patients who are matched on propensity score and calendar quarter of initiation. Event rates were calculated as the total number of patients in each treatment group who had the outcome during follow-up divided by the total person-years at risk in the cohort. For outcome definitions please refer the descriptions section of outcome 8 (major intracranial bleeding) and outcome 9 (major extracranial bleeding). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ischemic Stroke | From October 2010 to September 2015 (the study period) | The rate of ischemic stroke in patients who are matched on propensity score and calendar quarter of initiation. Event rates were calculated as the total number of patients in each treatment group who had the outcome during follow-up divided by the total person-years at risk in the cohort. The outcome definition includes following: As primary ICD-9 discharge diagnosis (Dx): 433.x1 Occlusion and stenosis of precerebral arteries with cerebral infarction, ICD-9 Dx 434.x1 Occlusion and stenosis of cerebral arteries with cerebral infarction |
| Hemorrhagic Stroke | From October 2010 to September 2015 (the study period) | The rate of hemorrhagic in patients who are matched on propensity score and calendar quarter of initiation. Event rates were calculated as the total number of patients in each treatment group who had the outcome during follow-up divided by the total person-years at risk in the cohort. The outcome definition includes following: As primary ICD-9 discharge diagnosis (Dx): 431.x Intracerebral hemorrhage (ICH) |
| Stroke Uncertain Classification | From October 2010 to September 2015 (the study period) | The rate of stroke uncertain classification in patients who are matched on propensity score and calendar quarter of initiation. Event rates were calculated as the total number of patients in each treatment group who had the outcome during follow-up divided by the total person-years at risk in the cohort. The outcome definition includes following: As primary ICD-9 discharge diagnosis (Dx): ICD-9 Dx code 436.x (acute, but ill-defined cerebrovascular disease). |
| Major Intracranial Bleeding | From October 2010 to September 2015 (the study period) | The rate of major intracranial bleeding in patients who are matched on propensity score and calendar quarter of initiation. Event rates were calculated as the total number of patients in each treatment group who had the outcome during follow-up divided by the total person-years at risk in the cohort. The outcome definition includes following: ICD-9 diagnosis: 430.x Subarachnoid hemorrhage (SAH), 431.x Intracerebral hemorrhage (ICH), 432.x other and unspecified intracranial hemorrhage including 432.1x - subdural hemorrhage |
| Major Extra-cranial Bleeding | From October 2010 to September 2015 (the study period) | The rate of major extracranial bleeding (Major upper GI bleed, major lower and unspecified GI bleed, major urogenital bleed, major other bleed) in patients who are matched on propensity score and calendar quarter of initiation. Event rates were calculated as total number of patients in each treatment group who had the outcome during follow-up divided by the total person-years at risk in the cohort. For outcome definitions please refer the descriptions section of outcome 11 (Major upper gastrointestinal bleeding), outcome 12 (Major lower gastrointestinal bleeding), outcome 13 (Major urogenital bleeding) and outcome 14 (Other major bleeding). |
| Major Gastrointestinal (GI) Bleeding | From October 2010 to September 2015 (the study period) | The rate of major gastrointestinal (GI) bleeding (Major upper GI bleeding, major lower/unspecified GI bleeding) in patients who are matched on propensity score and calendar quarter of initiation. Event rates were calculated as the total number of patients in each treatment group who had the outcome during follow-up divided by the total person-years at risk in the cohort. For outcome definitions please refer the descriptions section of outcome 11 (Major upper gastrointestinal bleeding) and outcome 12 (Major lower gastrointestinal bleeding). |
| Major Upper Gastrointestinal Bleeding | From October 2010 to September 2015 (the study period) | The rate of Major upper gastrointestinal bleeding in patients who are matched on propensity score and calendar quarter of initiation. Event rates were calculated as the total number of patients in each treatment group who had the outcome during follow-up divided by the total person-years at risk in the cohort. The outcome definition includes following: ICD-9 diagnoses: 531.0x, 531.2x, 531.4x, 531.6x, 532.0x, 532.2x, 532.4x, 532.6x, 533.0x, 533.2x, 533.4x, 533.6x, 534.0x, 534.2x, 534.4x, 534.6x, 578.0 OR ICD-9 procedure code 44.43 (endoscopic control of gastric or duodenal bleeding) OR Current Procedural Terminology (CPT) code 43255 (upper gastrointestinal endoscopy including esophagus, stomach, and either the duodenum and/or jejunum as appropriate with control of bleeding, any method). |
| Stroke or Systemic Embolism | From October 2010 to September 2015 (the study period) | The rate of stroke (hemorrhagic, ischemic or stroke of uncertain classification ) or systemic embolism in patients matched on propensity scores and calendar quarter of initiation. Event rates were calculated as the total number of patients in each treatment group who had the outcome during follow-up divided by the total person-years at risk in the cohort. For outcome definitions please refer the descriptions section of outcome 4 (Systemic embolism), outcome 5 (Ischemic stroke), outcome 6 (Hemorrhagic stroke) and outcome 7 (Stroke uncertain classification). |
| Major Urogenital Bleeding | From October 2010 to September 2015 (the study period) | The rate of major urogenital bleeding in patients who are matched on propensity score and calendar quarter of initiation. Event rates were calculated as the total number of patients in each treatment group who had the outcome during follow-up divided by the total person-years at risk in the cohort. The outcome definition includes following: ICD-9 diagnoses: Hematuria: ICD-9 Dx: 599.7, Excessive/frequent menstruation: ICD-9 Dx 626.2x and secondary diagnosis indicating acute bleeding: anemia (280.0, 285.1, 285.9). Across databases, only one event for dabigatran versus no event among warfarin initiators observed. Across database, four events for rivaroxaban versus no event among warfarin initiators observed. Across database, no events for apixaban and warfarin observed. Therefore HR estimate is not possible. |
| Other Major Bleeding | From October 2010 to September 2015 (the study period) | The rate of Other major bleeding in patients who are matched on propensity score and calendar quarter of initiation. Event rates were calculated as the total number of patients in each treatment group who had the outcome during follow-up divided by the total person-years at risk in the cohort. The outcome definition includes following: Other major bleeds: Hemathrosis: 719.1x, Hemopericardium: 423.0x, Hemoptysis: 786.3x, Epistaxis: 784.7x, Hemorrhage not specified 459.0x, Acute posthemorrhagic anemia 285.1x |
| Transient Ischemic Attack (TIA) | From October 2010 to September 2015 (the study period) | The rate of Transient Ischemic Attack (TIA) in patients who are matched on propensity score and calendar quarter of initiation. Event rates were calculated as the total number of patients in each treatment group who had the outcome during follow-up divided by the total person-years at risk in the cohort. The outcome definition includes following: ICD-9 Dx code 435.xx (transient cerebral ischemia) as the principal (primary) discharge diagnosis |
| Myocardial Infarction (MI) | From October 2010 to September 2015 (the study period) | The rate of Myocardial infarction (MI) in patients who are matched on propensity score and calendar quarter of initiation. Event rates were calculated as the total number of patients in each treatment group who had the outcome during follow-up divided by the total person-years at risk in the cohort. The outcome definition includes following: ICD-9 Dx 410.X (acute myocardial infarction) excluding 410.x2 (subsequent episode of care), as the principal (primary) or the next (secondary) diagnosis AND a length of stay (LOS) between 3-180 days, or death if LOS is \< 3 days |
| Venous Thromboembolism (VTE) | From October 2010 to September 2015 (the study period) | The rate of Venous Thromboembolism (VTE) in patients who are matched on propensity score and calendar quarter of initiation. Event rates were calculated as the total number of patients in each treatment group who had the outcome during follow-up divided by the total person-years at risk in the cohort. For outcome definitions please refer the descriptions section of outcome 18 (Deep vein thrombosis (DVT)) and outcome 19 (Pulmonary Embolism (PE)). |
| Deep Vein Thrombosis (DVT) | From October 2010 to September 2015 (the study period) | The rate of DVT in patients who are matched on propensity score and calendar quarter of initiation. Event rates were calculated as the total number of patients in each treatment group who had the outcome during follow-up divided by the total person-years at risk in the cohort. The outcome definition includes following: Validated algorithm: ICD-9 451.1x, ICD-9 451.2x,ICD-9 451.81, ICD-9 451.9x, ICD-9 453.1x, ICD-9 453.2x, ICD-9 453.8x, ICD-9 453.9x ; Not in the validated algorithm but will be included following Mini-Sentinel recommendation for VTE outcome: ICD-9 453.40 (Venous embolism and thrombosis of unspecified deep vessels of lower extremity (includes DVT), ICD-9 453.41 (Venous embolism and thrombosis of deep vessels of proximal lower extremity (includes femoral, iliac, popliteal, thigh, and upper leg), ICD-9 453.42 (Venous embolism and thrombosis of deep vessels of distal lower extremity (includes calf, lower leg, peroneal, and tibia), ICD-9 453.0 (Hepatic vein thrombosis) |
| Pulmonary Embolism (PE) | From October 2010 to September 2015 (the study period) | The rate of Pulmonary Embolism (PE) in patients who are matched on propensity score and calendar quarter of initiation. Event rates were calculated as the total number of patients in each treatment group who had the outcome during follow-up divided by the total person-years at risk in the cohort. The outcome definition includes following: ICD-9 415.1x (pulmonary embolism and infarction) |
| Major Lower Gastrointestinal Bleeding | From October 2010 to September 2015 (the study period) | The rate of lower gastrointestinal bleeding in patients who are matched on propensity score and calendar quarter of initiation. Event rates were calculated as the total number of patients in each treatment group who had the outcome during follow-up divided by the total person-years at risk in the cohort. The outcome definition includes following: Lower GI/unspecified GI site bleeds :Diverticulosis of small intestine with hemorrhage: 562.02, Diverticulitis of small intestine with hemorrhage: 562.03, Diverticulosis of colon with hemorrhage: 562.12, Diverticulitis of colon with hemorrhage: 562.13, Hemorrhage of rectum and anus: 569.3x, Angiodysplasia of intestine with hemorrhage: 569.85, Blood in stool: 578.1x, Hemorrhage of GI tract, unspecified: 578.9 |
| Systemic Embolism | From October 2010 to September 2015 (the study period) | The rate of systemic embolism in patients who are matched on propensity score and calendar quarter of initiation. Event rates were calculated as the total number of patients in each treatment group who had the outcome during follow-up divided by the total person-years at risk in the cohort. The outcome definition includes following: ICD-9 Diagnoses: 444.x Arterial embolism. |
Countries
United States
Participant flow
Recruitment details
Data for the patients included in this cohort study arose from two de-identified research databases, US MarketScan and Optum Research Database
Pre-assignment details
In this non-interventional study based on existing data, no patients were screened.
Participants by arm
| Arm | Count |
|---|---|
| Optum Clinformatics - Dabigatran Patients with non- valvular atrial fibrillation (NVAF) and new initiators of dabigatran, during October 2010 to September 2015 who were enrolled for a minimum of 12 months in Optum Clinformatics database before treatment initiation | 7,668 |
| Optum Clinformatics - Warfarin Patients with non- valvular atrial fibrillation (NVAF) and new initiators of warfarin, during October 2010 to September 2015 who were enrolled for a minimum of 12 months in Optum Clinformatics database before treatment initiation | 26,149 |
| Optum Clinformatics - Rivaroxaban Patients with non- valvular atrial fibrillation (NVAF) and new initiators of rivaroxaban, during July 2011 to September 2015 who were enrolled for a minimum of 12 months in Optum Clinformatics database before treatment initiation | 14,852 |
| Optum Clinformatics - Apixaban Patients with non- valvular atrial fibrillation (NVAF) and new initiators of apixaban, during January 2013 to September 2015 who were enrolled for a minimum of 12 months in Optum Clinformatics database before treatment initiation | 9,112 |
| MarketScan - Dabigatran Patients with non- valvular atrial fibrillation (NVAF) and new initiators of dabigatran, during October 2010 to September 2015 who were enrolled for a minimum of 12 months in MarketScan before treatment initiation | 27,456 |
| MarketScan - Warfarin Patients with non- valvular atrial fibrillation (NVAF) and new initiators of warfarin, during October 2010 to September 2015 who were enrolled for a minimum of 12 months in MarketScan before treatment initiation | 76,055 |
| MarketScan - Rivaroxaban Patients with non- valvular atrial fibrillation (NVAF) and new initiators of rivaroxaban, during July 2011 to September 2015 who were enrolled for a minimum of 12 months in MarketScan before treatment initiation | 40,207 |
| MarketScan - Apixaban Patients with non- valvular atrial fibrillation (NVAF) and new initiators of apixaban, during January 2013 to September 2015 who were enrolled for a minimum of 12 months in MarketScan before treatment initiation | 19,729 |
| Total | 221,228 |
Baseline characteristics
| Characteristic | Optum Clinformatics - Dabigatran | Optum Clinformatics - Warfarin | Optum Clinformatics - Rivaroxaban | Optum Clinformatics - Apixaban | MarketScan - Dabigatran | MarketScan - Warfarin | MarketScan - Rivaroxaban | MarketScan - Apixaban | Total |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 63.9 Years STANDARD_DEVIATION 11.3 | 69.9 Years STANDARD_DEVIATION 11.8 | 68.0 Years STANDARD_DEVIATION 11.9 | 71.9 Years STANDARD_DEVIATION 11.2 | 67.1 Years STANDARD_DEVIATION 12.1 | 71.0 Years STANDARD_DEVIATION 12.1 | 67.6 Years STANDARD_DEVIATION 12.2 | 69.4 Years STANDARD_DEVIATION 12.3 | 69.2 Years STANDARD_DEVIATION 12.2 |
| Race and Ethnicity Not Collected | — | — | — | — | — | — | — | — | 0 Participants |
| Sex: Female, Male Female | 2315 Participants | 10143 Participants | 5483 Participants | 3911 Participants | 9774 Participants | 29693 Participants | 15014 Participants | 7747 Participants | 84080 Participants |
| Sex: Female, Male Male | 5353 Participants | 16006 Participants | 9369 Participants | 5201 Participants | 17682 Participants | 46362 Participants | 25193 Participants | 11982 Participants | 137148 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 |
Outcome results
Primary
Major Bleeding
The rate of major bleeding (Major intracranial bleeding and major extracranial bleed ) in patients who are matched on propensity score and calendar quarter of initiation. Event rates were calculated as the total number of patients in each treatment group who had the outcome during follow-up divided by the total person-years at risk in the cohort. For outcome definitions please refer the descriptions section of outcome 8 (major intracranial bleeding) and outcome 9 (major extracranial bleeding).
Time frame: From October 2010 to September 2015 (the study period)
Population: Patients with non-valvular atrial fibrillation (NVAF) and new initiators of dabigatran and warfarin during October 2010 to September 2015 who were enrolled for a minimum of 12 months in Optum Clinformatics database or MarketScan before treatment initiation and matched on propensity scores (PS). Primary analysis represented an 'as treated' approach.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Optum Clinformatics - Dabigatran vs. Warfarin (Dabigatran) | Major Bleeding | 2.43 Incidence rate per 100 person-years |
| Optum Clinformatics - Dabigatran vs. Warfarin (Warfarin) | Major Bleeding | 5.23 Incidence rate per 100 person-years |
| MarketScan - Dabigatran vs. Warfarin (Dabigatran) | Major Bleeding | 4.36 Incidence rate per 100 person-years |
| MarketScan - Dabigatran vs. Warfarin (Warfarin) | Major Bleeding | 6.06 Incidence rate per 100 person-years |
| Optum Clinformatics - Rivaroxaban vs. Warfarin (Rivaroxaban) | Major Bleeding | 6.2 Incidence rate per 100 person-years |
| Optum Clinformatics - Rivaroxaban vs. Warfarin (Warfarin) | Major Bleeding | 6.3 Incidence rate per 100 person-years |
| MarketScan - Rivaroxaban vs. Warfarin (Rivaroxaban) | Major Bleeding | 6.9 Incidence rate per 100 person-years |
| MarketScan - Rivaroxaban vs. Warfarin (Warfarin) | Major Bleeding | 7.5 Incidence rate per 100 person-years |
| Optum Clinformatics - Apixaban vs. Warfarin (Apixaban) | Major Bleeding | 3.33 Incidence rate per 100 person-years |
| Optum Clinformatics - Apixaban vs. Warfarin (Warfarin) | Major Bleeding | 6.83 Incidence rate per 100 person-years |
| MarketScan - Apixaban vs. Warfarin (Apixaban) | Major Bleeding | 4.25 Incidence rate per 100 person-years |
| MarketScan - Apixaban vs. Warfarin (Warfarin) | Major Bleeding | 7.96 Incidence rate per 100 person-years |
Comparison: Optum Clinformatic-Dabigatran vs. Warfarin (as reference group).95% CI: [0.38, 0.69]Regression, Cox
Comparison: MarketScan-Dabigatran vs. Warfarin (as reference group).95% CI: [0.68, 0.86]Regression, Cox
Comparison: This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic-Dabigatran vs. Warfarin (as reference group).95% CI: [0.65, 0.8]Regression, Cox
Comparison: Optum Clinformatic- Rivaroxaban vs. Warfarin (as reference group).95% CI: [0.88, 1.26]Regression, Cox
Comparison: MarketScan-Rivaroxaban vs. Warfarin (as reference group).95% CI: [0.92, 1.12]Regression, Cox
Comparison: This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic- Rivaroxaban vs. Warfarin (as reference group).95% CI: [0.94, 1.12]Regression, Cox
Comparison: Optum Clinformatic- Apixaban vs. Warfarin (as reference group).95% CI: [0.39, 0.66]Regression, Cox
Comparison: MarketScan-Apixaban vs. Warfarin (as reference group).95% CI: [0.49, 0.68]Regression, Cox
Comparison: This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic- Apixaban vs. Warfarin (as reference group).95% CI: [0.49, 0.64]Regression, Cox
Primary
Stroke (Hemorrhagic, Ischemic, or Stroke of Uncertain Classification)
The rate of overall stroke (hemorrhagic, ischemic or stroke of uncertain classification ) in patients who are matched on propensity score and calendar quarter of initiation. Event rates were calculated as the total number of patients in each treatment group who had the outcome during follow-up divided by the total person-years at risk in the cohort. The outcome definition includes following: As primary International Classification of Diseases, Ninth Revision (ICD-9) discharge diagnosis (Dx): 431.x Intracerebral hemorrhage (ICH), 433.x1 Occlusion and stenosis of precerebral arteries with cerebral infarction, 434.x1 Occlusion and stenosis of cerebral arteries with cerebral infarction, 436.x Acute, but ill-defined cerebrovascular events.
Time frame: From October 2010 to September 2015 (the study period)
Population: Patients with non-valvular atrial fibrillation (NVAF) and new initiators of dabigatran and warfarin during October 2010 to September 2015 who were enrolled for a minimum of 12 months in Optum Clinformatics database or MarketScan before treatment initiation and matched on propensity scores (PS). Primary analysis represented an 'as treated' approach.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Optum Clinformatics - Dabigatran vs. Warfarin (Dabigatran) | Stroke (Hemorrhagic, Ischemic, or Stroke of Uncertain Classification) | 0.90 Incidence rate per 100 person-years |
| Optum Clinformatics - Dabigatran vs. Warfarin (Warfarin) | Stroke (Hemorrhagic, Ischemic, or Stroke of Uncertain Classification) | 1.01 Incidence rate per 100 person-years |
| MarketScan - Dabigatran vs. Warfarin (Dabigatran) | Stroke (Hemorrhagic, Ischemic, or Stroke of Uncertain Classification) | 0.64 Incidence rate per 100 person-years |
| MarketScan - Dabigatran vs. Warfarin (Warfarin) | Stroke (Hemorrhagic, Ischemic, or Stroke of Uncertain Classification) | 0.99 Incidence rate per 100 person-years |
| Optum Clinformatics - Rivaroxaban vs. Warfarin (Rivaroxaban) | Stroke (Hemorrhagic, Ischemic, or Stroke of Uncertain Classification) | 0.80 Incidence rate per 100 person-years |
| Optum Clinformatics - Rivaroxaban vs. Warfarin (Warfarin) | Stroke (Hemorrhagic, Ischemic, or Stroke of Uncertain Classification) | 1.02 Incidence rate per 100 person-years |
| MarketScan - Rivaroxaban vs. Warfarin (Rivaroxaban) | Stroke (Hemorrhagic, Ischemic, or Stroke of Uncertain Classification) | 0.78 Incidence rate per 100 person-years |
| MarketScan - Rivaroxaban vs. Warfarin (Warfarin) | Stroke (Hemorrhagic, Ischemic, or Stroke of Uncertain Classification) | 1.09 Incidence rate per 100 person-years |
| Optum Clinformatics - Apixaban vs. Warfarin (Apixaban) | Stroke (Hemorrhagic, Ischemic, or Stroke of Uncertain Classification) | 1.08 Incidence rate per 100 person-years |
| Optum Clinformatics - Apixaban vs. Warfarin (Warfarin) | Stroke (Hemorrhagic, Ischemic, or Stroke of Uncertain Classification) | 1.26 Incidence rate per 100 person-years |
| MarketScan - Apixaban vs. Warfarin (Apixaban) | Stroke (Hemorrhagic, Ischemic, or Stroke of Uncertain Classification) | 0.62 Incidence rate per 100 person-years |
| MarketScan - Apixaban vs. Warfarin (Warfarin) | Stroke (Hemorrhagic, Ischemic, or Stroke of Uncertain Classification) | 1.16 Incidence rate per 100 person-years |
Comparison: Optum Clinformatic-Dabigatran vs. Warfarin (as reference group).95% CI: [0.57, 1.76]Regression, Cox
Comparison: MarketScan-Dabigatran vs. Warfarin (as reference group).95% CI: [0.52, 0.94]Regression, Cox
Comparison: This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic-Dabigatran vs. Warfarin (as reference group).95% CI: [0.58, 0.98]Regression, Cox
Comparison: Optum Clinformatic- Rivaroxaban vs. Warfarin (as reference group).95% CI: [0.53, 1.35]Regression, Cox
Comparison: MarketScan-Rivaroxaban vs. Warfarin (as reference group).95% CI: [0.57, 0.98]Regression, Cox
Comparison: This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic- Rivaroxaban vs. Warfarin (as reference group).95% CI: [0.61, 0.98]Regression, Cox
Comparison: Optum Clinformatic- Apixaban vs. Warfarin (as reference group).95% CI: [0.53, 1.51]Regression, Cox
Comparison: MarketScan-Apixaban vs. Warfarin (as reference group).95% CI: [0.38, 0.89]Regression, Cox
Comparison: This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic- Apixaban vs. Warfarin (as reference group).95% CI: [0.5, 0.96]Regression, Cox
Secondary
Deep Vein Thrombosis (DVT)
The rate of DVT in patients who are matched on propensity score and calendar quarter of initiation. Event rates were calculated as the total number of patients in each treatment group who had the outcome during follow-up divided by the total person-years at risk in the cohort. The outcome definition includes following: Validated algorithm: ICD-9 451.1x, ICD-9 451.2x,ICD-9 451.81, ICD-9 451.9x, ICD-9 453.1x, ICD-9 453.2x, ICD-9 453.8x, ICD-9 453.9x ; Not in the validated algorithm but will be included following Mini-Sentinel recommendation for VTE outcome: ICD-9 453.40 (Venous embolism and thrombosis of unspecified deep vessels of lower extremity (includes DVT), ICD-9 453.41 (Venous embolism and thrombosis of deep vessels of proximal lower extremity (includes femoral, iliac, popliteal, thigh, and upper leg), ICD-9 453.42 (Venous embolism and thrombosis of deep vessels of distal lower extremity (includes calf, lower leg, peroneal, and tibia), ICD-9 453.0 (Hepatic vein thrombosis)
Time frame: From October 2010 to September 2015 (the study period)
Population: Patients with non-valvular atrial fibrillation (NVAF) and new initiators of dabigatran and warfarin during October 2010 to September 2015 who were enrolled for a minimum of 12 months in Optum Clinformatics database or MarketScan before treatment initiation and matched on propensity scores (PS). Primary analysis represented an 'as treated' approach.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Optum Clinformatics - Dabigatran vs. Warfarin (Dabigatran) | Deep Vein Thrombosis (DVT) | 0.46 Incidence rate per 100 person-years |
| Optum Clinformatics - Dabigatran vs. Warfarin (Warfarin) | Deep Vein Thrombosis (DVT) | 0.78 Incidence rate per 100 person-years |
| MarketScan - Dabigatran vs. Warfarin (Dabigatran) | Deep Vein Thrombosis (DVT) | 0.78 Incidence rate per 100 person-years |
| MarketScan - Dabigatran vs. Warfarin (Warfarin) | Deep Vein Thrombosis (DVT) | 1.09 Incidence rate per 100 person-years |
| Optum Clinformatics - Rivaroxaban vs. Warfarin (Rivaroxaban) | Deep Vein Thrombosis (DVT) | 0.41 Incidence rate per 100 person-years |
| Optum Clinformatics - Rivaroxaban vs. Warfarin (Warfarin) | Deep Vein Thrombosis (DVT) | 0.75 Incidence rate per 100 person-years |
Comparison: This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic-Dabigatran vs. Warfarin (as reference group).95% CI: [0.47, 0.88]Regression, Cox
Comparison: This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic- Rivaroxaban vs. Warfarin (as reference group).95% CI: [0.65, 1.04]Regression, Cox
Comparison: This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic- Apixaban vs. Warfarin (as reference group).95% CI: [0.39, 0.92]Regression, Cox
Secondary
Hemorrhagic Stroke
The rate of hemorrhagic in patients who are matched on propensity score and calendar quarter of initiation. Event rates were calculated as the total number of patients in each treatment group who had the outcome during follow-up divided by the total person-years at risk in the cohort. The outcome definition includes following: As primary ICD-9 discharge diagnosis (Dx): 431.x Intracerebral hemorrhage (ICH)
Time frame: From October 2010 to September 2015 (the study period)
Population: Patients with non-valvular atrial fibrillation (NVAF) and new initiators of dabigatran and warfarin during October 2010 to September 2015 who were enrolled for a minimum of 12 months in Optum Clinformatics database or MarketScan before treatment initiation and matched on propensity scores (PS). Primary analysis represented an 'as treated' approach.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Optum Clinformatics - Dabigatran vs. Warfarin (Dabigatran) | Hemorrhagic Stroke | 0.07 Incidence rate per 100 person-years |
| Optum Clinformatics - Dabigatran vs. Warfarin (Warfarin) | Hemorrhagic Stroke | 0.19 Incidence rate per 100 person-years |
| MarketScan - Dabigatran vs. Warfarin (Dabigatran) | Hemorrhagic Stroke | 0.18 Incidence rate per 100 person-years |
| MarketScan - Dabigatran vs. Warfarin (Warfarin) | Hemorrhagic Stroke | 0.18 Incidence rate per 100 person-years |
| Optum Clinformatics - Rivaroxaban vs. Warfarin (Rivaroxaban) | Hemorrhagic Stroke | 0.15 Incidence rate per 100 person-years |
| Optum Clinformatics - Rivaroxaban vs. Warfarin (Warfarin) | Hemorrhagic Stroke | 0.18 Incidence rate per 100 person-years |
Comparison: This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic-Dabigatran vs. Warfarin (as reference group).95% CI: [0.18, 0.78]Regression, Cox
Comparison: This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic- Rivaroxaban vs. Warfarin (as reference group).95% CI: [0.58, 1.72]Regression, Cox
Comparison: This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic- Apixaban vs. Warfarin (as reference group).95% CI: [0.38, 1.87]Regression, Cox
Secondary
Ischemic Stroke
The rate of ischemic stroke in patients who are matched on propensity score and calendar quarter of initiation. Event rates were calculated as the total number of patients in each treatment group who had the outcome during follow-up divided by the total person-years at risk in the cohort. The outcome definition includes following: As primary ICD-9 discharge diagnosis (Dx): 433.x1 Occlusion and stenosis of precerebral arteries with cerebral infarction, ICD-9 Dx 434.x1 Occlusion and stenosis of cerebral arteries with cerebral infarction
Time frame: From October 2010 to September 2015 (the study period)
Population: Patients with non-valvular atrial fibrillation (NVAF) and new initiators of dabigatran and warfarin during October 2010 to September 2015 who were enrolled for a minimum of 12 months in Optum Clinformatics database or MarketScan before treatment initiation and matched on propensity scores (PS). Primary analysis represented an 'as treated' approach.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Optum Clinformatics - Dabigatran vs. Warfarin (Dabigatran) | Ischemic Stroke | 0.63 Incidence rate per 100 person-years |
| Optum Clinformatics - Dabigatran vs. Warfarin (Warfarin) | Ischemic Stroke | 0.80 Incidence rate per 100 person-years |
| MarketScan - Dabigatran vs. Warfarin (Dabigatran) | Ischemic Stroke | 0.63 Incidence rate per 100 person-years |
| MarketScan - Dabigatran vs. Warfarin (Warfarin) | Ischemic Stroke | 0.90 Incidence rate per 100 person-years |
| Optum Clinformatics - Rivaroxaban vs. Warfarin (Rivaroxaban) | Ischemic Stroke | 0.61 Incidence rate per 100 person-years |
| Optum Clinformatics - Rivaroxaban vs. Warfarin (Warfarin) | Ischemic Stroke | 1.03 Incidence rate per 100 person-years |
Comparison: This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic- Apixaban vs. Warfarin (as reference group).95% CI: [0.45, 0.94]Regression, Cox
Comparison: This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic-Dabigatran vs. Warfarin (as reference group).95% CI: [0.63, 1.12]Regression, Cox
Comparison: This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic- Rivaroxaban vs. Warfarin (as reference group).95% CI: [0.57, 0.96]Regression, Cox
Secondary
Major Extra-cranial Bleeding
The rate of major extracranial bleeding (Major upper GI bleed, major lower and unspecified GI bleed, major urogenital bleed, major other bleed) in patients who are matched on propensity score and calendar quarter of initiation. Event rates were calculated as total number of patients in each treatment group who had the outcome during follow-up divided by the total person-years at risk in the cohort. For outcome definitions please refer the descriptions section of outcome 11 (Major upper gastrointestinal bleeding), outcome 12 (Major lower gastrointestinal bleeding), outcome 13 (Major urogenital bleeding) and outcome 14 (Other major bleeding).
Time frame: From October 2010 to September 2015 (the study period)
Population: Patients with non-valvular atrial fibrillation (NVAF) and new initiators of dabigatran and warfarin during October 2010 to September 2015 who were enrolled for a minimum of 12 months in Optum Clinformatics database or MarketScan before treatment initiation and matched on propensity scores (PS). Primary analysis represented an 'as treated' approach.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Optum Clinformatics - Dabigatran vs. Warfarin (Dabigatran) | Major Extra-cranial Bleeding | 3.78 Incidence rate per 100 person-years |
| Optum Clinformatics - Dabigatran vs. Warfarin (Warfarin) | Major Extra-cranial Bleeding | 5.37 Incidence rate per 100 person-years |
| MarketScan - Dabigatran vs. Warfarin (Dabigatran) | Major Extra-cranial Bleeding | 6.31 Incidence rate per 100 person-years |
| MarketScan - Dabigatran vs. Warfarin (Warfarin) | Major Extra-cranial Bleeding | 6.54 Incidence rate per 100 person-years |
| Optum Clinformatics - Rivaroxaban vs. Warfarin (Rivaroxaban) | Major Extra-cranial Bleeding | 3.51 Incidence rate per 100 person-years |
| Optum Clinformatics - Rivaroxaban vs. Warfarin (Warfarin) | Major Extra-cranial Bleeding | 6.92 Incidence rate per 100 person-years |
Comparison: This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic-Dabigatran vs. Warfarin (as reference group).95% CI: [0.67, 0.84]Regression, Cox
Comparison: This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic- Rivaroxaban vs. Warfarin (as reference group).95% CI: [0.97, 1.16]Regression, Cox
Comparison: This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic- Apixaban vs. Warfarin (as reference group).95% CI: [0.47, 0.63]Regression, Cox
Secondary
Major Gastrointestinal (GI) Bleeding
The rate of major gastrointestinal (GI) bleeding (Major upper GI bleeding, major lower/unspecified GI bleeding) in patients who are matched on propensity score and calendar quarter of initiation. Event rates were calculated as the total number of patients in each treatment group who had the outcome during follow-up divided by the total person-years at risk in the cohort. For outcome definitions please refer the descriptions section of outcome 11 (Major upper gastrointestinal bleeding) and outcome 12 (Major lower gastrointestinal bleeding).
Time frame: From October 2010 to September 2015 (the study period)
Population: Patients with non-valvular atrial fibrillation (NVAF) and new initiators of dabigatran and warfarin during October 2010 to September 2015 who were enrolled for a minimum of 12 months in Optum Clinformatics database or MarketScan before treatment initiation and matched on propensity scores (PS). Primary analysis represented an 'as treated' approach.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Optum Clinformatics - Dabigatran vs. Warfarin (Dabigatran) | Major Gastrointestinal (GI) Bleeding | 2.39 Incidence rate per 100 person-years |
| Optum Clinformatics - Dabigatran vs. Warfarin (Warfarin) | Major Gastrointestinal (GI) Bleeding | 2.82 Incidence rate per 100 person-years |
| MarketScan - Dabigatran vs. Warfarin (Dabigatran) | Major Gastrointestinal (GI) Bleeding | 3.82 Incidence rate per 100 person-years |
| MarketScan - Dabigatran vs. Warfarin (Warfarin) | Major Gastrointestinal (GI) Bleeding | 3.43 Incidence rate per 100 person-years |
| Optum Clinformatics - Rivaroxaban vs. Warfarin (Rivaroxaban) | Major Gastrointestinal (GI) Bleeding | 1.99 Incidence rate per 100 person-years |
| Optum Clinformatics - Rivaroxaban vs. Warfarin (Warfarin) | Major Gastrointestinal (GI) Bleeding | 3.59 Incidence rate per 100 person-years |
Comparison: This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic-Dabigatran vs. Warfarin (as reference group).95% CI: [0.77, 1.04]Regression, Cox
Comparison: This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic- Rivaroxaban vs. Warfarin (as reference group).95% CI: [1.07, 1.36]Regression, Cox
Comparison: This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic- Apixaban vs. Warfarin (as reference group).95% CI: [0.48, 0.72]Regression, Cox
Secondary
Major Intracranial Bleeding
The rate of major intracranial bleeding in patients who are matched on propensity score and calendar quarter of initiation. Event rates were calculated as the total number of patients in each treatment group who had the outcome during follow-up divided by the total person-years at risk in the cohort. The outcome definition includes following: ICD-9 diagnosis: 430.x Subarachnoid hemorrhage (SAH), 431.x Intracerebral hemorrhage (ICH), 432.x other and unspecified intracranial hemorrhage including 432.1x - subdural hemorrhage
Time frame: From October 2010 to September 2015 (the study period)
Population: Patients with non-valvular atrial fibrillation (NVAF) and new initiators of dabigatran and warfarin during October 2010 to September 2015 who were enrolled for a minimum of 12 months in Optum Clinformatics database or MarketScan before treatment initiation and matched on propensity scores (PS). Primary analysis represented an 'as treated' approach.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Optum Clinformatics - Dabigatran vs. Warfarin (Dabigatran) | Major Intracranial Bleeding | 0.21 Incidence rate per 100 person-years |
| Optum Clinformatics - Dabigatran vs. Warfarin (Warfarin) | Major Intracranial Bleeding | 0.58 Incidence rate per 100 person-years |
| MarketScan - Dabigatran vs. Warfarin (Dabigatran) | Major Intracranial Bleeding | 0.44 Incidence rate per 100 person-years |
| MarketScan - Dabigatran vs. Warfarin (Warfarin) | Major Intracranial Bleeding | 0.66 Incidence rate per 100 person-years |
| Optum Clinformatics - Rivaroxaban vs. Warfarin (Rivaroxaban) | Major Intracranial Bleeding | 0.45 Incidence rate per 100 person-years |
| Optum Clinformatics - Rivaroxaban vs. Warfarin (Warfarin) | Major Intracranial Bleeding | 0.69 Incidence rate per 100 person-years |
Comparison: This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic-Dabigatran vs. Warfarin (as reference group).95% CI: [0.25, 0.59]Regression, Cox
Comparison: This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic- Rivaroxaban vs. Warfarin (as reference group).95% CI: [0.51, 0.95]Regression, Cox
Comparison: This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic- Apixaban vs. Warfarin (as reference group).95% CI: [0.43, 1.03]Regression, Cox
Secondary
Major Lower Gastrointestinal Bleeding
The rate of lower gastrointestinal bleeding in patients who are matched on propensity score and calendar quarter of initiation. Event rates were calculated as the total number of patients in each treatment group who had the outcome during follow-up divided by the total person-years at risk in the cohort. The outcome definition includes following: Lower GI/unspecified GI site bleeds :Diverticulosis of small intestine with hemorrhage: 562.02, Diverticulitis of small intestine with hemorrhage: 562.03, Diverticulosis of colon with hemorrhage: 562.12, Diverticulitis of colon with hemorrhage: 562.13, Hemorrhage of rectum and anus: 569.3x, Angiodysplasia of intestine with hemorrhage: 569.85, Blood in stool: 578.1x, Hemorrhage of GI tract, unspecified: 578.9
Time frame: From October 2010 to September 2015 (the study period)
Population: Patients with non-valvular atrial fibrillation (NVAF) and new initiators of dabigatran and warfarin during October 2010 to September 2015 who were enrolled for a minimum of 12 months in Optum Clinformatics database or MarketScan before treatment initiation and matched on propensity scores (PS). Primary analysis represented an 'as treated' approach.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Optum Clinformatics - Dabigatran vs. Warfarin (Dabigatran) | Major Lower Gastrointestinal Bleeding | 2.18 Incidence rate per 100 person-years |
| Optum Clinformatics - Dabigatran vs. Warfarin (Warfarin) | Major Lower Gastrointestinal Bleeding | 2.48 Incidence rate per 100 person-years |
| MarketScan - Dabigatran vs. Warfarin (Dabigatran) | Major Lower Gastrointestinal Bleeding | 3.40 Incidence rate per 100 person-years |
| MarketScan - Dabigatran vs. Warfarin (Warfarin) | Major Lower Gastrointestinal Bleeding | 3.09 Incidence rate per 100 person-years |
| Optum Clinformatics - Rivaroxaban vs. Warfarin (Rivaroxaban) | Major Lower Gastrointestinal Bleeding | 1.61 Incidence rate per 100 person-years |
| Optum Clinformatics - Rivaroxaban vs. Warfarin (Warfarin) | Major Lower Gastrointestinal Bleeding | 3.17 Incidence rate per 100 person-years |
Comparison: This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic-Dabigatran vs. Warfarin (as reference group).95% CI: [0.79, 1.08]Regression, Cox
Comparison: This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic- Rivaroxaban vs. Warfarin (as reference group).95% CI: [1.05, 1.35]Regression, Cox
Comparison: This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic- Apixaban vs. Warfarin (as reference group).95% CI: [0.44, 0.67]Regression, Cox
Secondary
Major Upper Gastrointestinal Bleeding
The rate of Major upper gastrointestinal bleeding in patients who are matched on propensity score and calendar quarter of initiation. Event rates were calculated as the total number of patients in each treatment group who had the outcome during follow-up divided by the total person-years at risk in the cohort. The outcome definition includes following: ICD-9 diagnoses: 531.0x, 531.2x, 531.4x, 531.6x, 532.0x, 532.2x, 532.4x, 532.6x, 533.0x, 533.2x, 533.4x, 533.6x, 534.0x, 534.2x, 534.4x, 534.6x, 578.0 OR ICD-9 procedure code 44.43 (endoscopic control of gastric or duodenal bleeding) OR Current Procedural Terminology (CPT) code 43255 (upper gastrointestinal endoscopy including esophagus, stomach, and either the duodenum and/or jejunum as appropriate with control of bleeding, any method).
Time frame: From October 2010 to September 2015 (the study period)
Population: Patients with non-valvular atrial fibrillation (NVAF) and new initiators of dabigatran and warfarin during October 2010 to September 2015 who were enrolled for a minimum of 12 months in Optum Clinformatics database or MarketScan before treatment initiation and matched on propensity scores (PS). Primary analysis represented an 'as treated' approach.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Optum Clinformatics - Dabigatran vs. Warfarin (Dabigatran) | Major Upper Gastrointestinal Bleeding | 0.51 Incidence rate per 100 person-years |
| Optum Clinformatics - Dabigatran vs. Warfarin (Warfarin) | Major Upper Gastrointestinal Bleeding | 0.90 Incidence rate per 100 person-years |
| MarketScan - Dabigatran vs. Warfarin (Dabigatran) | Major Upper Gastrointestinal Bleeding | 0.99 Incidence rate per 100 person-years |
| MarketScan - Dabigatran vs. Warfarin (Warfarin) | Major Upper Gastrointestinal Bleeding | 0.88 Incidence rate per 100 person-years |
| Optum Clinformatics - Rivaroxaban vs. Warfarin (Rivaroxaban) | Major Upper Gastrointestinal Bleeding | 0.64 Incidence rate per 100 person-years |
| Optum Clinformatics - Rivaroxaban vs. Warfarin (Warfarin) | Major Upper Gastrointestinal Bleeding | 0.89 Incidence rate per 100 person-years |
Comparison: This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic-Dabigatran vs. Warfarin (as reference group).95% CI: [0.44, 0.8]Regression, Cox
Comparison: This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic- Rivaroxaban vs. Warfarin (as reference group).95% CI: [0.98, 1.57]Regression, Cox
Comparison: This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic- Apixaban vs. Warfarin (as reference group).95% CI: [0.54, 1.14]Regression, Cox
Secondary
Major Urogenital Bleeding
The rate of major urogenital bleeding in patients who are matched on propensity score and calendar quarter of initiation. Event rates were calculated as the total number of patients in each treatment group who had the outcome during follow-up divided by the total person-years at risk in the cohort. The outcome definition includes following: ICD-9 diagnoses: Hematuria: ICD-9 Dx: 599.7, Excessive/frequent menstruation: ICD-9 Dx 626.2x and secondary diagnosis indicating acute bleeding: anemia (280.0, 285.1, 285.9). Across databases, only one event for dabigatran versus no event among warfarin initiators observed. Across database, four events for rivaroxaban versus no event among warfarin initiators observed. Across database, no events for apixaban and warfarin observed. Therefore HR estimate is not possible.
Time frame: From October 2010 to September 2015 (the study period)
Population: Patients with non-valvular atrial fibrillation (NVAF) and new initiators of dabigatran and warfarin during October 2010 to September 2015 who were enrolled for a minimum of 12 months in Optum Clinformatics database or MarketScan before treatment initiation and matched on propensity scores (PS). Primary analysis represented an 'as treated' approach.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Optum Clinformatics - Dabigatran vs. Warfarin (Dabigatran) | Major Urogenital Bleeding | 0.01 Incidence rate per 100 person-years |
| Optum Clinformatics - Dabigatran vs. Warfarin (Warfarin) | Major Urogenital Bleeding | 0.00 Incidence rate per 100 person-years |
| MarketScan - Dabigatran vs. Warfarin (Dabigatran) | Major Urogenital Bleeding | 0.02 Incidence rate per 100 person-years |
| MarketScan - Dabigatran vs. Warfarin (Warfarin) | Major Urogenital Bleeding | 0.00 Incidence rate per 100 person-years |
| Optum Clinformatics - Rivaroxaban vs. Warfarin (Rivaroxaban) | Major Urogenital Bleeding | 0.00 Incidence rate per 100 person-years |
| Optum Clinformatics - Rivaroxaban vs. Warfarin (Warfarin) | Major Urogenital Bleeding | 0.00 Incidence rate per 100 person-years |
Secondary
Myocardial Infarction (MI)
The rate of Myocardial infarction (MI) in patients who are matched on propensity score and calendar quarter of initiation. Event rates were calculated as the total number of patients in each treatment group who had the outcome during follow-up divided by the total person-years at risk in the cohort. The outcome definition includes following: ICD-9 Dx 410.X (acute myocardial infarction) excluding 410.x2 (subsequent episode of care), as the principal (primary) or the next (secondary) diagnosis AND a length of stay (LOS) between 3-180 days, or death if LOS is \< 3 days
Time frame: From October 2010 to September 2015 (the study period)
Population: Patients with non-valvular atrial fibrillation (NVAF) and new initiators of dabigatran and warfarin during October 2010 to September 2015 who were enrolled for a minimum of 12 months in Optum Clinformatics database or MarketScan before treatment initiation and matched on propensity scores (PS). Primary analysis represented an 'as treated' approach.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Optum Clinformatics - Dabigatran vs. Warfarin (Dabigatran) | Myocardial Infarction (MI) | 0.48 Incidence rate per 100 person-years |
| Optum Clinformatics - Dabigatran vs. Warfarin (Warfarin) | Myocardial Infarction (MI) | 0.60 Incidence rate per 100 person-years |
| MarketScan - Dabigatran vs. Warfarin (Dabigatran) | Myocardial Infarction (MI) | 0.53 Incidence rate per 100 person-years |
| MarketScan - Dabigatran vs. Warfarin (Warfarin) | Myocardial Infarction (MI) | 0.65 Incidence rate per 100 person-years |
| Optum Clinformatics - Rivaroxaban vs. Warfarin (Rivaroxaban) | Myocardial Infarction (MI) | 0.57 Incidence rate per 100 person-years |
| Optum Clinformatics - Rivaroxaban vs. Warfarin (Warfarin) | Myocardial Infarction (MI) | 0.74 Incidence rate per 100 person-years |
Comparison: This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic-Dabigatran vs. Warfarin (as reference group).95% CI: [0.6, 1.15]Regression, Cox
Comparison: This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic- Rivaroxaban vs. Warfarin (as reference group).95% CI: [0.63, 1.14]Regression, Cox
Comparison: This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic- Apixaban vs. Warfarin (as reference group).95% CI: [0.53, 1.18]Regression, Cox
Secondary
Other Major Bleeding
The rate of Other major bleeding in patients who are matched on propensity score and calendar quarter of initiation. Event rates were calculated as the total number of patients in each treatment group who had the outcome during follow-up divided by the total person-years at risk in the cohort. The outcome definition includes following: Other major bleeds: Hemathrosis: 719.1x, Hemopericardium: 423.0x, Hemoptysis: 786.3x, Epistaxis: 784.7x, Hemorrhage not specified 459.0x, Acute posthemorrhagic anemia 285.1x
Time frame: From October 2010 to September 2015 (the study period)
Population: Patients with non-valvular atrial fibrillation (NVAF) and new initiators of dabigatran and warfarin during October 2010 to September 2015 who were enrolled for a minimum of 12 months in Optum Clinformatics database or MarketScan before treatment initiation and matched on propensity scores (PS). Primary analysis represented an 'as treated' approach.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Optum Clinformatics - Dabigatran vs. Warfarin (Dabigatran) | Other Major Bleeding | 2.32 Incidence rate per 100 person-years |
| Optum Clinformatics - Dabigatran vs. Warfarin (Warfarin) | Other Major Bleeding | 3.65 Incidence rate per 100 person-years |
| MarketScan - Dabigatran vs. Warfarin (Dabigatran) | Other Major Bleeding | 4.33 Incidence rate per 100 person-years |
| MarketScan - Dabigatran vs. Warfarin (Warfarin) | Other Major Bleeding | 4.59 Incidence rate per 100 person-years |
| Optum Clinformatics - Rivaroxaban vs. Warfarin (Rivaroxaban) | Other Major Bleeding | 2.54 Incidence rate per 100 person-years |
| Optum Clinformatics - Rivaroxaban vs. Warfarin (Warfarin) | Other Major Bleeding | 4.86 Incidence rate per 100 person-years |
Comparison: This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic-Dabigatran vs. Warfarin (as reference group).95% CI: [0.59, 78]Regression, Cox
Comparison: This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic- Rivaroxaban vs. Warfarin (as reference group).95% CI: [0.93, 1.16]Regression, Cox
Comparison: This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic- Apixaban vs. Warfarin (as reference group).95% CI: [0.47, 0.67]Regression, Cox
Secondary
Pulmonary Embolism (PE)
The rate of Pulmonary Embolism (PE) in patients who are matched on propensity score and calendar quarter of initiation. Event rates were calculated as the total number of patients in each treatment group who had the outcome during follow-up divided by the total person-years at risk in the cohort. The outcome definition includes following: ICD-9 415.1x (pulmonary embolism and infarction)
Time frame: From October 2010 to September 2015 (the study period)
Population: Patients with non-valvular atrial fibrillation (NVAF) and new initiators of dabigatran and warfarin during October 2010 to September 2015 who were enrolled for a minimum of 12 months in Optum Clinformatics database or MarketScan before treatment initiation and matched on propensity scores (PS). Primary analysis represented an 'as treated' approach.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Optum Clinformatics - Dabigatran vs. Warfarin (Dabigatran) | Pulmonary Embolism (PE) | 0.29 Incidence rate per 100 person-years |
| Optum Clinformatics - Dabigatran vs. Warfarin (Warfarin) | Pulmonary Embolism (PE) | 0.46 Incidence rate per 100 person-years |
| MarketScan - Dabigatran vs. Warfarin (Dabigatran) | Pulmonary Embolism (PE) | 0.54 Incidence rate per 100 person-years |
| MarketScan - Dabigatran vs. Warfarin (Warfarin) | Pulmonary Embolism (PE) | 0.81 Incidence rate per 100 person-years |
| Optum Clinformatics - Rivaroxaban vs. Warfarin (Rivaroxaban) | Pulmonary Embolism (PE) | 0.22 Incidence rate per 100 person-years |
| Optum Clinformatics - Rivaroxaban vs. Warfarin (Warfarin) | Pulmonary Embolism (PE) | 0.62 Incidence rate per 100 person-years |
Comparison: This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic- Dabigatran vs. Warfarin (as reference group).95% CI: [0.47, 1.04]Regression, Cox
Comparison: This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic- Rivaroxaban vs. Warfarin (as reference group).95% CI: [0.6, 1.05]Regression, Cox
Comparison: This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic- Apixaban vs. Warfarin (as reference group).95% CI: [0.24, 0.73]Regression, Cox
Secondary
Stroke or Systemic Embolism
The rate of stroke (hemorrhagic, ischemic or stroke of uncertain classification ) or systemic embolism in patients matched on propensity scores and calendar quarter of initiation. Event rates were calculated as the total number of patients in each treatment group who had the outcome during follow-up divided by the total person-years at risk in the cohort. For outcome definitions please refer the descriptions section of outcome 4 (Systemic embolism), outcome 5 (Ischemic stroke), outcome 6 (Hemorrhagic stroke) and outcome 7 (Stroke uncertain classification).
Time frame: From October 2010 to September 2015 (the study period)
Population: Patients with non-valvular atrial fibrillation (NVAF) and new initiators of dabigatran and warfarin during October 2010 to September 2015 who were enrolled for a minimum of 12 months in Optum Clinformatics database or MarketScan before treatment initiation and matched on propensity scores (PS). Primary analysis represented an 'as treated' approach.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Optum Clinformatics - Dabigatran vs. Warfarin (Dabigatran) | Stroke or Systemic Embolism | 0.92 Incidence rate per 100 person-years |
| Optum Clinformatics - Dabigatran vs. Warfarin (Warfarin) | Stroke or Systemic Embolism | 1.13 Incidence rate per 100 person-years |
| MarketScan - Dabigatran vs. Warfarin (Dabigatran) | Stroke or Systemic Embolism | 1.00 Incidence rate per 100 person-years |
| MarketScan - Dabigatran vs. Warfarin (Warfarin) | Stroke or Systemic Embolism | 1.29 Incidence rate per 100 person-years |
| Optum Clinformatics - Rivaroxaban vs. Warfarin (Rivaroxaban) | Stroke or Systemic Embolism | 0.81 Incidence rate per 100 person-years |
| Optum Clinformatics - Rivaroxaban vs. Warfarin (Warfarin) | Stroke or Systemic Embolism | 1.36 Incidence rate per 100 person-years |
Comparison: This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic-Dabigatran vs. Warfarin (as reference group).95% CI: [0.69, 1.11]Regression, Cox
Comparison: This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic- Rivaroxaban vs. Warfarin (as reference group).95% CI: [0.66, 1.02]Regression, Cox
Comparison: This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic- Apixaban vs. Warfarin (as reference group).95% CI: [0.47, 0.88]Regression, Cox
Secondary
Stroke Uncertain Classification
The rate of stroke uncertain classification in patients who are matched on propensity score and calendar quarter of initiation. Event rates were calculated as the total number of patients in each treatment group who had the outcome during follow-up divided by the total person-years at risk in the cohort. The outcome definition includes following: As primary ICD-9 discharge diagnosis (Dx): ICD-9 Dx code 436.x (acute, but ill-defined cerebrovascular disease).
Time frame: From October 2010 to September 2015 (the study period)
Population: Patients with non-valvular atrial fibrillation (NVAF) and new initiators of dabigatran and warfarin during October 2010 to September 2015 who were enrolled for a minimum of 12 months in Optum Clinformatics database or MarketScan before treatment initiation and matched on propensity scores (PS). Primary analysis represented an 'as treated' approach.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Optum Clinformatics - Dabigatran vs. Warfarin (Dabigatran) | Stroke Uncertain Classification | 0.00 Incidence rate per 100 person-years |
| Optum Clinformatics - Dabigatran vs. Warfarin (Warfarin) | Stroke Uncertain Classification | 0.00 Incidence rate per 100 person-years |
| MarketScan - Dabigatran vs. Warfarin (Dabigatran) | Stroke Uncertain Classification | 0.00 Incidence rate per 100 person-years |
| MarketScan - Dabigatran vs. Warfarin (Warfarin) | Stroke Uncertain Classification | 0.00 Incidence rate per 100 person-years |
| Optum Clinformatics - Rivaroxaban vs. Warfarin (Rivaroxaban) | Stroke Uncertain Classification | 0.00 Incidence rate per 100 person-years |
| Optum Clinformatics - Rivaroxaban vs. Warfarin (Warfarin) | Stroke Uncertain Classification | 0.00 Incidence rate per 100 person-years |
Secondary
Systemic Embolism
The rate of systemic embolism in patients who are matched on propensity score and calendar quarter of initiation. Event rates were calculated as the total number of patients in each treatment group who had the outcome during follow-up divided by the total person-years at risk in the cohort. The outcome definition includes following: ICD-9 Diagnoses: 444.x Arterial embolism.
Time frame: From October 2010 to September 2015 (the study period)
Population: Patients with non-valvular atrial fibrillation (NVAF) and new initiators of dabigatran and warfarin during October 2010 to September 2015 who were enrolled for a minimum of 12 months in Optum Clinformatics database or MarketScan before treatment initiation and matched on propensity scores (PS). Primary analysis represented an 'as treated' approach.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Optum Clinformatics - Dabigatran vs. Warfarin (Dabigatran) | Systemic Embolism | 0.23 Incidence rate per 100 person-years |
| Optum Clinformatics - Dabigatran vs. Warfarin (Warfarin) | Systemic Embolism | 0.14 Incidence rate per 100 person-years |
| MarketScan - Dabigatran vs. Warfarin (Dabigatran) | Systemic Embolism | 0.21 Incidence rate per 100 person-years |
| MarketScan - Dabigatran vs. Warfarin (Warfarin) | Systemic Embolism | 0.22 Incidence rate per 100 person-years |
| Optum Clinformatics - Rivaroxaban vs. Warfarin (Rivaroxaban) | Systemic Embolism | 0.05 Incidence rate per 100 person-years |
| Optum Clinformatics - Rivaroxaban vs. Warfarin (Warfarin) | Systemic Embolism | 0.17 Incidence rate per 100 person-years |
Comparison: This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic-Dabigatran vs. Warfarin (as reference group).95% CI: [1.03, 3.3]Regression, Cox
Comparison: This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic- Rivaroxaban vs. Warfarin (as reference group).95% CI: [0.65, 1.71]Regression, Cox
Comparison: This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic- Apixaban vs. Warfarin (as reference group).95% CI: [0.1, 0.96]Regression, Cox
Secondary
Transient Ischemic Attack (TIA)
The rate of Transient Ischemic Attack (TIA) in patients who are matched on propensity score and calendar quarter of initiation. Event rates were calculated as the total number of patients in each treatment group who had the outcome during follow-up divided by the total person-years at risk in the cohort. The outcome definition includes following: ICD-9 Dx code 435.xx (transient cerebral ischemia) as the principal (primary) discharge diagnosis
Time frame: From October 2010 to September 2015 (the study period)
Population: Patients with non-valvular atrial fibrillation (NVAF) and new initiators of dabigatran and warfarin during October 2010 to September 2015 who were enrolled for a minimum of 12 months in Optum Clinformatics database or MarketScan before treatment initiation and matched on propensity scores (PS). Primary analysis represented an 'as treated' approach.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Optum Clinformatics - Dabigatran vs. Warfarin (Dabigatran) | Transient Ischemic Attack (TIA) | 0.21 Incidence rate per 100 person-years |
| Optum Clinformatics - Dabigatran vs. Warfarin (Warfarin) | Transient Ischemic Attack (TIA) | 0.43 Incidence rate per 100 person-years |
| MarketScan - Dabigatran vs. Warfarin (Dabigatran) | Transient Ischemic Attack (TIA) | 0.26 Incidence rate per 100 person-years |
| MarketScan - Dabigatran vs. Warfarin (Warfarin) | Transient Ischemic Attack (TIA) | 0.31 Incidence rate per 100 person-years |
| Optum Clinformatics - Rivaroxaban vs. Warfarin (Rivaroxaban) | Transient Ischemic Attack (TIA) | 0.22 Incidence rate per 100 person-years |
| Optum Clinformatics - Rivaroxaban vs. Warfarin (Warfarin) | Transient Ischemic Attack (TIA) | 0.32 Incidence rate per 100 person-years |
Comparison: This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic-Dabigatran vs. Warfarin (as reference group).95% CI: [0.34, 0.82]Regression, Cox
Comparison: This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic- Rivaroxaban vs. Warfarin (as reference group).95% CI: [0.55, 1.29]Regression, Cox
Comparison: This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic- Apixaban vs. Warfarin (as reference group).95% CI: [0.41, 1.42]Regression, Cox
Secondary
Venous Thromboembolism (VTE)
The rate of Venous Thromboembolism (VTE) in patients who are matched on propensity score and calendar quarter of initiation. Event rates were calculated as the total number of patients in each treatment group who had the outcome during follow-up divided by the total person-years at risk in the cohort. For outcome definitions please refer the descriptions section of outcome 18 (Deep vein thrombosis (DVT)) and outcome 19 (Pulmonary Embolism (PE)).
Time frame: From October 2010 to September 2015 (the study period)
Population: Patients with non-valvular atrial fibrillation (NVAF) and new initiators of dabigatran and warfarin during October 2010 to September 2015 who were enrolled for a minimum of 12 months in Optum Clinformatics database or MarketScan before treatment initiation and matched on propensity scores (PS). Primary analysis represented an 'as treated' approach.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Optum Clinformatics - Dabigatran vs. Warfarin (Dabigatran) | Venous Thromboembolism (VTE) | 0.67 Incidence rate per 100 person-years |
| Optum Clinformatics - Dabigatran vs. Warfarin (Warfarin) | Venous Thromboembolism (VTE) | 1.14 Incidence rate per 100 person-years |
| MarketScan - Dabigatran vs. Warfarin (Dabigatran) | Venous Thromboembolism (VTE) | 1.20 Incidence rate per 100 person-years |
| MarketScan - Dabigatran vs. Warfarin (Warfarin) | Venous Thromboembolism (VTE) | 1.65 Incidence rate per 100 person-years |
| Optum Clinformatics - Rivaroxaban vs. Warfarin (Rivaroxaban) | Venous Thromboembolism (VTE) | 0.57 Incidence rate per 100 person-years |
| Optum Clinformatics - Rivaroxaban vs. Warfarin (Warfarin) | Venous Thromboembolism (VTE) | 1.21 Incidence rate per 100 person-years |
Comparison: This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic-Rivaroxaban vs. Warfarin (as reference group).95% CI: [0.69, 1.01]Regression, Cox
Comparison: This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic-Dabigatran vs. Warfarin (as reference group).95% CI: [0.5, 0.84]Regression, Cox
Comparison: This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic- Apixaban vs. Warfarin (as reference group).95% CI: [0.37, 0.76]Regression, Cox