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Sequential Expansion of Comparative Effectiveness of Anticoagulants

Sponsor
Boehringer Ingelheim (Industry)
Overall Status
Completed
CT.gov ID
NCT02081807
Collaborator
(none)
221,228
Enrollment
1
Location
43.9
Actual Duration (Months)
5043.9
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase

    Study Design

    Study Type:
    Observational
    Actual Enrollment :
    221228 participants
    Observational Model:
    Cohort
    Time Perspective:
    Retrospective
    Official Title:
    Sequential Expansion of Comparative Effectiveness of Oral Anticoagulants: A Cohort Study
    Actual Study Start Date :
    Mar 7, 2014
    Actual Primary Completion Date :
    Nov 1, 2017
    Actual Study Completion Date :
    Nov 1, 2017

    Arms and Interventions

    Arm Intervention/Treatment
    Dabigatran
    Warfarin

    Outcome Measures

    Primary Outcome Measures

    1. 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.

    2. 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 Outcome Measures

    1. 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).

    2. 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.

    3. 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

    4. 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)

    5. 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).

    6. 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

    7. 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).

    8. 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).

    9. 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).

    10. 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

    11. 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.

    12. 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

    13. 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

    14. 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

    15. 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)).

    16. 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)

    17. 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)

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Brigham and Women's Hospital Boston Massachusetts United States 02120

    Sponsors and Collaborators

    • Boehringer Ingelheim

    Investigators

    • Study Chair: Boehringer Ingelheim, Boehringer Ingelheim

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Boehringer Ingelheim
    ClinicalTrials.gov Identifier:
    NCT02081807
    Other Study ID Numbers:
    • 1160.207
    First Posted:
    Mar 7, 2014
    Last Update Posted:
    Oct 2, 2019
    Last Verified:
    Sep 1, 2019
    Additional relevant MeSH terms:
    Atrial Fibrillation

    Study Results

    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 Detail In this non-interventional study based on existing data, no patients were screened.
    Arm/Group Title Optum Clinformatics - Dabigatran Optum Clinformatics - Warfarin Optum Clinformatics - Rivaroxaban Optum Clinformatics - Apixaban MarketScan - Dabigatran MarketScan - Warfarin MarketScan - Rivaroxaban MarketScan - Apixaban
    Arm/Group Description 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 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 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 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 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 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 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 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
    Period Title: Overall Study
    STARTED 7668 26149 14852 9112 27456 76055 40207 19729
    COMPLETED 7668 26149 14852 9112 27456 76055 40207 19729
    NOT COMPLETED 0 0 0 0 0 0 0 0

    Baseline Characteristics

    Arm/Group Title Optum Clinformatics - Dabigatran Optum Clinformatics - Warfarin Optum Clinformatics - Rivaroxaban Optum Clinformatics - Apixaban MarketScan - Dabigatran MarketScan - Warfarin MarketScan - Rivaroxaban MarketScan - Apixaban Total
    Arm/Group Description 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 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 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 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 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 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 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 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 Total of all reporting groups
    Overall Participants 7668 26149 14852 9112 27456 76055 40207 19729 221228
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    63.9
    (11.3)
    69.9
    (11.8)
    68.0
    (11.9)
    71.9
    (11.2)
    67.1
    (12.1)
    71.0
    (12.1)
    67.6
    (12.2)
    69.4
    (12.3)
    69.2
    (12.2)
    Sex: Female, Male (Count of Participants)
    Female
    2315
    30.2%
    10143
    38.8%
    5483
    36.9%
    3911
    42.9%
    9774
    35.6%
    29693
    39%
    15014
    37.3%
    7747
    39.3%
    84080
    38%
    Male
    5353
    69.8%
    16006
    61.2%
    9369
    63.1%
    5201
    57.1%
    17682
    64.4%
    46362
    61%
    25193
    62.7%
    11982
    60.7%
    137148
    62%
    Race and Ethnicity Not Collected (Count of Participants)
    Count of Participants [Participants]
    0
    0%

    Outcome Measures

    1. Primary Outcome
    Title Stroke (Hemorrhagic, Ischemic, or Stroke of Uncertain Classification)
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Optum Clinformatics - Dabigatran vs. Warfarin (Dabigatran) Optum Clinformatics - Dabigatran vs. Warfarin (Warfarin) MarketScan - Dabigatran vs. Warfarin (Dabigatran) MarketScan - Dabigatran vs. Warfarin (Warfarin) Optum Clinformatics - Rivaroxaban vs. Warfarin (Rivaroxaban) Optum Clinformatics - Rivaroxaban vs. Warfarin (Warfarin) MarketScan - Rivaroxaban vs. Warfarin (Rivaroxaban) MarketScan - Rivaroxaban vs. Warfarin (Warfarin) Optum Clinformatics - Apixaban vs. Warfarin (Apixaban) Optum Clinformatics - Apixaban vs. Warfarin (Warfarin) MarketScan - Apixaban vs. Warfarin (Apixaban) MarketScan - Apixaban vs. Warfarin (Warfarin)
    Arm/Group Description 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 and matched on propensity scores with 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 and matched on propensity scores with 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 and matched on propensity scores with 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 and matched on propensity scores with dabigatran 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 and matched on propensity scores with warfarin Patients with non- valvular atrial fibrillation (NVAF) and new initiators of warfarin, during July 2011 to September 2015 who were enrolled for a minimum of 12 months in Optum Clinformatics database before treatment initiation and matched on propensity scores with 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 and matched on propensity scores with warfarin Patients with non- valvular atrial fibrillation (NVAF) and new initiators of warfarin, during July 2011 to September 2015 who were enrolled for a minimum of 12 months in MarketScan before treatment initiation and matched on propensity scores with rivaroxaban 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 and matched on propensity scores with warfarin Patients with non- valvular atrial fibrillation (NVAF) and new initiators of warfarin, during January 2013 to September 2015 who were enrolled for a minimum of 12 months in Optum Clinformatics database before treatment initiation and matched on propensity scores with 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 and matched on propensity scores with warfarin Patients with non- valvular atrial fibrillation (NVAF) and new initiators of warfarin, during January 2013 to September 2015 who were enrolled for a minimum of 12 months in MarketScan before treatment initiation and matched on propensity scores with apixaban
    Measure Participants 6125 6125 23323 23323 10373 10373 25147 25147 7065 7065 12523 12523
    Number (95% Confidence Interval) [Incidence rate per 100 person-years]
    0.90
    1.01
    0.64
    0.99
    0.80
    1.02
    0.78
    1.09
    1.08
    1.26
    0.62
    1.16
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Optum Clinformatics - Dabigatran vs. Warfarin (Dabigatran), Optum Clinformatics - Dabigatran vs. Warfarin (Warfarin)
    Comments Optum Clinformatic-Dabigatran vs. Warfarin (as reference group).
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.00
    Confidence Interval (2-Sided) 95%
    0.57 to 1.76
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection MarketScan - Dabigatran vs. Warfarin (Dabigatran), MarketScan - Dabigatran vs. Warfarin (Warfarin)
    Comments MarketScan-Dabigatran vs. Warfarin (as reference group).
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.69
    Confidence Interval (2-Sided) 95%
    0.52 to 0.94
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Optum Clinformatics - Dabigatran vs. Warfarin (Dabigatran), Optum Clinformatics - Dabigatran vs. Warfarin (Warfarin), MarketScan - Dabigatran vs. Warfarin (Dabigatran), MarketScan - Dabigatran vs. Warfarin (Warfarin)
    Comments This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic-Dabigatran vs. Warfarin (as reference group).
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.75
    Confidence Interval (2-Sided) 95%
    0.58 to 0.98
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Optum Clinformatics - Rivaroxaban vs. Warfarin (Rivaroxaban), Optum Clinformatics - Rivaroxaban vs. Warfarin (Warfarin)
    Comments Optum Clinformatic- Rivaroxaban vs. Warfarin (as reference group).
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.84
    Confidence Interval (2-Sided) 95%
    0.53 to 1.35
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection MarketScan - Rivaroxaban vs. Warfarin (Rivaroxaban), MarketScan - Rivaroxaban vs. Warfarin (Warfarin)
    Comments MarketScan-Rivaroxaban vs. Warfarin (as reference group).
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.75
    Confidence Interval (2-Sided) 95%
    0.57 to 0.98
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Optum Clinformatics - Rivaroxaban vs. Warfarin (Rivaroxaban), Optum Clinformatics - Rivaroxaban vs. Warfarin (Warfarin), MarketScan - Rivaroxaban vs. Warfarin (Rivaroxaban), MarketScan - Rivaroxaban vs. Warfarin (Warfarin)
    Comments This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic- Rivaroxaban vs. Warfarin (as reference group).
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.77
    Confidence Interval (2-Sided) 95%
    0.61 to 0.98
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Optum Clinformatics - Apixaban vs. Warfarin (Apixaban), Optum Clinformatics - Apixaban vs. Warfarin (Warfarin)
    Comments Optum Clinformatic- Apixaban vs. Warfarin (as reference group).
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.90
    Confidence Interval (2-Sided) 95%
    0.53 to 1.51
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection MarketScan - Apixaban vs. Warfarin (Apixaban), MarketScan - Apixaban vs. Warfarin (Warfarin)
    Comments MarketScan-Apixaban vs. Warfarin (as reference group).
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.58
    Confidence Interval (2-Sided) 95%
    0.38 to 0.89
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Optum Clinformatics - Apixaban vs. Warfarin (Apixaban), Optum Clinformatics - Apixaban vs. Warfarin (Warfarin), MarketScan - Apixaban vs. Warfarin (Apixaban), MarketScan - Apixaban vs. Warfarin (Warfarin)
    Comments This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic- Apixaban vs. Warfarin (as reference group).
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.69
    Confidence Interval (2-Sided) 95%
    0.50 to 0.96
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Primary Outcome
    Title Major Bleeding
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Optum Clinformatics - Dabigatran vs. Warfarin (Dabigatran) Optum Clinformatics - Dabigatran vs. Warfarin (Warfarin) MarketScan - Dabigatran vs. Warfarin (Dabigatran) MarketScan - Dabigatran vs. Warfarin (Warfarin) Optum Clinformatics - Rivaroxaban vs. Warfarin (Rivaroxaban) Optum Clinformatics - Rivaroxaban vs. Warfarin (Warfarin) MarketScan - Rivaroxaban vs. Warfarin (Rivaroxaban) MarketScan - Rivaroxaban vs. Warfarin (Warfarin) Optum Clinformatics - Apixaban vs. Warfarin (Apixaban) Optum Clinformatics - Apixaban vs. Warfarin (Warfarin) MarketScan - Apixaban vs. Warfarin (Apixaban) MarketScan - Apixaban vs. Warfarin (Warfarin)
    Arm/Group Description 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 and matched on propensity scores with 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 and matched on propensity scores with 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 and matched on propensity scores with 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 and matched on propensity scores with dabigatran 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 and matched on propensity scores with warfarin Patients with non- valvular atrial fibrillation (NVAF) and new initiators of warfarin, during July 2011 to September 2015 who were enrolled for a minimum of 12 months in Optum Clinformatics database before treatment initiation and matched on propensity scores with 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 and matched on propensity scores with warfarin Patients with non- valvular atrial fibrillation (NVAF) and new initiators of warfarin, during July 2011 to September 2015 who were enrolled for a minimum of 12 months in MarketScan before treatment initiation and matched on propensity scores with rivaroxaban 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 and matched on propensity scores with warfarin Patients with non- valvular atrial fibrillation (NVAF) and new initiators of warfarin, during January 2013 to September 2015 who were enrolled for a minimum of 12 months in Optum Clinformatics database before treatment initiation and matched on propensity scores with 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 and matched on propensity scores with warfarin Patients with non- valvular atrial fibrillation (NVAF) and new initiators of warfarin, during January 2013 to September 2015 who were enrolled for a minimum of 12 months in MarketScan before treatment initiation and matched on propensity scores with apixaban
    Measure Participants 6125 6125 23323 23323 10373 10373 25147 25147 7065 7065 12523 12523
    Number (95% Confidence Interval) [Incidence rate per 100 person-years]
    2.43
    5.23
    4.36
    6.06
    6.2
    6.3
    6.9
    7.5
    3.33
    6.83
    4.25
    7.96
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Optum Clinformatics - Dabigatran vs. Warfarin (Dabigatran), Optum Clinformatics - Dabigatran vs. Warfarin (Warfarin)
    Comments Optum Clinformatic-Dabigatran vs. Warfarin (as reference group).
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.51
    Confidence Interval (2-Sided) 95%
    0.38 to 0.69
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection MarketScan - Dabigatran vs. Warfarin (Dabigatran), MarketScan - Dabigatran vs. Warfarin (Warfarin)
    Comments MarketScan-Dabigatran vs. Warfarin (as reference group).
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.76
    Confidence Interval (2-Sided) 95%
    0.68 to 0.86
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Optum Clinformatics - Dabigatran vs. Warfarin (Dabigatran), Optum Clinformatics - Dabigatran vs. Warfarin (Warfarin), MarketScan - Dabigatran vs. Warfarin (Dabigatran), MarketScan - Dabigatran vs. Warfarin (Warfarin)
    Comments This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic-Dabigatran vs. Warfarin (as reference group).
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.72
    Confidence Interval (2-Sided) 95%
    0.65 to 0.80
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Optum Clinformatics - Rivaroxaban vs. Warfarin (Rivaroxaban), Optum Clinformatics - Rivaroxaban vs. Warfarin (Warfarin)
    Comments Optum Clinformatic- Rivaroxaban vs. Warfarin (as reference group).
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.06
    Confidence Interval (2-Sided) 95%
    0.88 to 1.26
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection MarketScan - Rivaroxaban vs. Warfarin (Rivaroxaban), MarketScan - Rivaroxaban vs. Warfarin (Warfarin)
    Comments MarketScan-Rivaroxaban vs. Warfarin (as reference group).
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.01
    Confidence Interval (2-Sided) 95%
    0.92 to 1.12
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Optum Clinformatics - Rivaroxaban vs. Warfarin (Rivaroxaban), Optum Clinformatics - Rivaroxaban vs. Warfarin (Warfarin), MarketScan - Rivaroxaban vs. Warfarin (Rivaroxaban), MarketScan - Rivaroxaban vs. Warfarin (Warfarin)
    Comments This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic- Rivaroxaban vs. Warfarin (as reference group).
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.02
    Confidence Interval (2-Sided) 95%
    0.94 to 1.12
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Optum Clinformatics - Apixaban vs. Warfarin (Apixaban), Optum Clinformatics - Apixaban vs. Warfarin (Warfarin)
    Comments Optum Clinformatic- Apixaban vs. Warfarin (as reference group).
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.51
    Confidence Interval (2-Sided) 95%
    0.39 to 0.66
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection MarketScan - Apixaban vs. Warfarin (Apixaban), MarketScan - Apixaban vs. Warfarin (Warfarin)
    Comments MarketScan-Apixaban vs. Warfarin (as reference group).
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.58
    Confidence Interval (2-Sided) 95%
    0.49 to 0.68
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Optum Clinformatics - Apixaban vs. Warfarin (Apixaban), Optum Clinformatics - Apixaban vs. Warfarin (Warfarin), MarketScan - Apixaban vs. Warfarin (Apixaban), MarketScan - Apixaban vs. Warfarin (Warfarin)
    Comments This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic- Apixaban vs. Warfarin (as reference group).
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.56
    Confidence Interval (2-Sided) 95%
    0.49 to 0.64
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    3. Secondary Outcome
    Title Stroke or Systemic Embolism
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Dabigatran vs. Warfarin (Dabigatran) Dabigatran vs. Warfarin (Warfarin) Rivaroxaban vs. Warfarin (Rivaroxaban) Rivaroxaban vs. Warfarin (Warfarin) Apixaban vs. Warfarin (Apixaban) Apixaban vs. Warfarin (Warfarin)
    Arm/Group Description 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 or MarketScan before treatment initiation and matched on propensity scores with 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 or MarketScan before treatment initiation and matched on propensity scores with dabigatran 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 or MarketScan before treatment initiation and matched on propensity scores with warfarin Patients with non- valvular atrial fibrillation (NVAF) and new initiators of warfarin, during July 2011 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 with rivaroxaban 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 or MarketScan before treatment initiation and matched on propensity scores with warfarin Patients with non- valvular atrial fibrillation (NVAF) and new initiators of warfarin, during January 2013 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 with apixaban
    Measure Participants 29448 29448 35520 35520 19588 19588
    Number (95% Confidence Interval) [Incidence rate per 100 person-years]
    0.92
    1.13
    1.00
    1.29
    0.81
    1.36
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Optum Clinformatics - Dabigatran vs. Warfarin (Dabigatran), Optum Clinformatics - Dabigatran vs. Warfarin (Warfarin)
    Comments This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic-Dabigatran vs. Warfarin (as reference group).
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.87
    Confidence Interval (2-Sided) 95%
    0.69 to 1.11
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection MarketScan - Dabigatran vs. Warfarin (Dabigatran), MarketScan - Dabigatran vs. Warfarin (Warfarin)
    Comments This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic- Rivaroxaban vs. Warfarin (as reference group).
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.82
    Confidence Interval (2-Sided) 95%
    0.66 to 1.02
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Optum Clinformatics - Rivaroxaban vs. Warfarin (Rivaroxaban), Optum Clinformatics - Rivaroxaban vs. Warfarin (Warfarin)
    Comments This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic- Apixaban vs. Warfarin (as reference group).
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.64
    Confidence Interval (2-Sided) 95%
    0.47 to 0.88
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    4. Secondary Outcome
    Title Systemic Embolism
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Dabigatran vs. Warfarin (Dabigatran) Dabigatran vs. Warfarin (Warfarin) Rivaroxaban vs. Warfarin (Rivaroxaban) Rivaroxaban vs. Warfarin (Warfarin) Apixaban vs. Warfarin (Apixaban) Apixaban vs. Warfarin (Warfarin)
    Arm/Group Description 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 or MarketScan before treatment initiation and matched on propensity scores with 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 or MarketScan before treatment initiation and matched on propensity scores with dabigatran 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 or MarketScan before treatment initiation and matched on propensity scores with warfarin Patients with non- valvular atrial fibrillation (NVAF) and new initiators of warfarin, during July 2011 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 with rivaroxaban 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 or MarketScan before treatment initiation and matched on propensity scores with warfarin Patients with non- valvular atrial fibrillation (NVAF) and new initiators of warfarin, during January 2013 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 with apixaban
    Measure Participants 29448 29448 35520 35520 19588 19588
    Number (95% Confidence Interval) [Incidence rate per 100 person-years]
    0.23
    0.14
    0.21
    0.22
    0.05
    0.17
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Optum Clinformatics - Dabigatran vs. Warfarin (Dabigatran), Optum Clinformatics - Dabigatran vs. Warfarin (Warfarin)
    Comments This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic-Dabigatran vs. Warfarin (as reference group).
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.85
    Confidence Interval (2-Sided) 95%
    1.03 to 3.30
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection MarketScan - Dabigatran vs. Warfarin (Dabigatran), MarketScan - Dabigatran vs. Warfarin (Warfarin)
    Comments This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic- Rivaroxaban vs. Warfarin (as reference group).
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.05
    Confidence Interval (2-Sided) 95%
    0.65 to 1.71
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Optum Clinformatics - Rivaroxaban vs. Warfarin (Rivaroxaban), Optum Clinformatics - Rivaroxaban vs. Warfarin (Warfarin)
    Comments This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic- Apixaban vs. Warfarin (as reference group).
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.31
    Confidence Interval (2-Sided) 95%
    0.10 to 0.96
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    5. Secondary Outcome
    Title Ischemic Stroke
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Dabigatran vs. Warfarin (Dabigatran) Dabigatran vs. Warfarin (Warfarin) Rivaroxaban vs. Warfarin (Rivaroxaban) Rivaroxaban vs. Warfarin (Warfarin) Apixaban vs. Warfarin (Apixaban) Apixaban vs. Warfarin (Warfarin)
    Arm/Group Description 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 or MarketScan before treatment initiation and matched on propensity scores with 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 or MarketScan before treatment initiation and matched on propensity scores with dabigatran 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 or MarketScan before treatment initiation and matched on propensity scores with warfarin Patients with non- valvular atrial fibrillation (NVAF) and new initiators of warfarin, during July 2011 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 with rivaroxaban 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 or MarketScan before treatment initiation and matched on propensity scores with warfarin Patients with non- valvular atrial fibrillation (NVAF) and new initiators of warfarin, during January 2013 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 with apixaban
    Measure Participants 29448 29448 35520 35520 19588 19588
    Number (95% Confidence Interval) [Incidence rate per 100 person-years]
    0.63
    0.80
    0.63
    0.90
    0.61
    1.03
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Optum Clinformatics - Dabigatran vs. Warfarin (Dabigatran), Optum Clinformatics - Dabigatran vs. Warfarin (Warfarin)
    Comments This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic-Dabigatran vs. Warfarin (as reference group).
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.84
    Confidence Interval (2-Sided) 95%
    0.63 to 1.12
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection MarketScan - Dabigatran vs. Warfarin (Dabigatran), MarketScan - Dabigatran vs. Warfarin (Warfarin)
    Comments This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic- Rivaroxaban vs. Warfarin (as reference group).
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.74
    Confidence Interval (2-Sided) 95%
    0.57 to 0.96
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Optum Clinformatics - Rivaroxaban vs. Warfarin (Rivaroxaban), Optum Clinformatics - Rivaroxaban vs. Warfarin (Warfarin)
    Comments This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic- Apixaban vs. Warfarin (as reference group).
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.65
    Confidence Interval (2-Sided) 95%
    0.45 to 0.94
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    6. Secondary Outcome
    Title Hemorrhagic Stroke
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Dabigatran vs. Warfarin (Dabigatran) Dabigatran vs. Warfarin (Warfarin) Rivaroxaban vs. Warfarin (Rivaroxaban) Rivaroxaban vs. Warfarin (Warfarin) Apixaban vs. Warfarin (Apixaban) Apixaban vs. Warfarin (Warfarin)
    Arm/Group Description 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 or MarketScan before treatment initiation and matched on propensity scores with 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 or MarketScan before treatment initiation and matched on propensity scores with dabigatran 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 or MarketScan before treatment initiation and matched on propensity scores with warfarin Patients with non- valvular atrial fibrillation (NVAF) and new initiators of warfarin, during July 2011 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 with rivaroxaban 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 or MarketScan before treatment initiation and matched on propensity scores with warfarin Patients with non- valvular atrial fibrillation (NVAF) and new initiators of warfarin, during January 2013 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 with apixaban
    Measure Participants 29448 29448 35520 35520 19588 19588
    Number (95% Confidence Interval) [Incidence rate per 100 person-years]
    0.07
    0.19
    0.18
    0.18
    0.15
    0.18
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Optum Clinformatics - Dabigatran vs. Warfarin (Dabigatran), Optum Clinformatics - Dabigatran vs. Warfarin (Warfarin)
    Comments This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic-Dabigatran vs. Warfarin (as reference group).
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.37
    Confidence Interval (2-Sided) 95%
    0.18 to 0.78
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection MarketScan - Dabigatran vs. Warfarin (Dabigatran), MarketScan - Dabigatran vs. Warfarin (Warfarin)
    Comments This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic- Rivaroxaban vs. Warfarin (as reference group).
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.00
    Confidence Interval (2-Sided) 95%
    0.58 to 1.72
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Optum Clinformatics - Rivaroxaban vs. Warfarin (Rivaroxaban), Optum Clinformatics - Rivaroxaban vs. Warfarin (Warfarin)
    Comments This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic- Apixaban vs. Warfarin (as reference group).
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.85
    Confidence Interval (2-Sided) 95%
    0.38 to 1.87
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    7. Secondary Outcome
    Title Stroke Uncertain Classification
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Dabigatran vs. Warfarin (Dabigatran) Dabigatran vs. Warfarin (Warfarin) Rivaroxaban vs. Warfarin (Rivaroxaban) Rivaroxaban vs. Warfarin (Warfarin) Apixaban vs. Warfarin (Apixaban) Apixaban vs. Warfarin (Warfarin)
    Arm/Group Description 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 or MarketScan before treatment initiation and matched on propensity scores with 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 or MarketScan before treatment initiation and matched on propensity scores with dabigatran 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 or MarketScan before treatment initiation and matched on propensity scores with warfarin Patients with non- valvular atrial fibrillation (NVAF) and new initiators of warfarin, during July 2011 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 with rivaroxaban 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 or MarketScan before treatment initiation and matched on propensity scores with warfarin Patients with non- valvular atrial fibrillation (NVAF) and new initiators of warfarin, during January 2013 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 with apixaban
    Measure Participants 29448 29448 35520 35520 19588 19588
    Number (95% Confidence Interval) [Incidence rate per 100 person-years]
    0.00
    0.00
    0.00
    0.00
    0.00
    0.00
    8. Secondary Outcome
    Title Major Intracranial Bleeding
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Dabigatran vs. Warfarin (Dabigatran) Dabigatran vs. Warfarin (Warfarin) Rivaroxaban vs. Warfarin (Rivaroxaban) Rivaroxaban vs. Warfarin (Warfarin) Apixaban vs. Warfarin (Apixaban) Apixaban vs. Warfarin (Warfarin)
    Arm/Group Description 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 or MarketScan before treatment initiation and matched on propensity scores with 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 or MarketScan before treatment initiation and matched on propensity scores with dabigatran 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 or MarketScan before treatment initiation and matched on propensity scores with warfarin Patients with non- valvular atrial fibrillation (NVAF) and new initiators of warfarin, during July 2011 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 with rivaroxaban 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 or MarketScan before treatment initiation and matched on propensity scores with warfarin Patients with non- valvular atrial fibrillation (NVAF) and new initiators of warfarin, during January 2013 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 with apixaban
    Measure Participants 29448 29448 35520 35520 19588 19588
    Number (95% Confidence Interval) [Incidence rate per 100 person-years]
    0.21
    0.58
    0.44
    0.66
    0.45
    0.69
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Optum Clinformatics - Dabigatran vs. Warfarin (Dabigatran), Optum Clinformatics - Dabigatran vs. Warfarin (Warfarin)
    Comments This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic-Dabigatran vs. Warfarin (as reference group).
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.39
    Confidence Interval (2-Sided) 95%
    0.25 to 0.59
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection MarketScan - Dabigatran vs. Warfarin (Dabigatran), MarketScan - Dabigatran vs. Warfarin (Warfarin)
    Comments This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic- Rivaroxaban vs. Warfarin (as reference group).
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.70
    Confidence Interval (2-Sided) 95%
    0.51 to 0.95
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Optum Clinformatics - Rivaroxaban vs. Warfarin (Rivaroxaban), Optum Clinformatics - Rivaroxaban vs. Warfarin (Warfarin)
    Comments This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic- Apixaban vs. Warfarin (as reference group).
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.67
    Confidence Interval (2-Sided) 95%
    0.43 to 1.03
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    9. Secondary Outcome
    Title Major Extra-cranial Bleeding
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Dabigatran vs. Warfarin (Dabigatran) Dabigatran vs. Warfarin (Warfarin) Rivaroxaban vs. Warfarin (Rivaroxaban) Rivaroxaban vs. Warfarin (Warfarin) Apixaban vs. Warfarin (Apixaban) Apixaban vs. Warfarin (Warfarin)
    Arm/Group Description 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 or MarketScan before treatment initiation and matched on propensity scores with 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 or MarketScan before treatment initiation and matched on propensity scores with dabigatran 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 or MarketScan before treatment initiation and matched on propensity scores with warfarin Patients with non- valvular atrial fibrillation (NVAF) and new initiators of warfarin, during July 2011 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 with rivaroxaban 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 or MarketScan before treatment initiation and matched on propensity scores with warfarin Patients with non- valvular atrial fibrillation (NVAF) and new initiators of warfarin, during January 2013 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 with apixaban
    Measure Participants 29448 29448 35520 35520 19588 19588
    Number (95% Confidence Interval) [Incidence rate per 100 person-years]
    3.78
    5.37
    6.31
    6.54
    3.51
    6.92
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Optum Clinformatics - Dabigatran vs. Warfarin (Dabigatran), Optum Clinformatics - Dabigatran vs. Warfarin (Warfarin)
    Comments This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic-Dabigatran vs. Warfarin (as reference group).
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.75
    Confidence Interval (2-Sided) 95%
    0.67 to 0.84
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection MarketScan - Dabigatran vs. Warfarin (Dabigatran), MarketScan - Dabigatran vs. Warfarin (Warfarin)
    Comments This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic- Rivaroxaban vs. Warfarin (as reference group).
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.06
    Confidence Interval (2-Sided) 95%
    0.97 to 1.16
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Optum Clinformatics - Rivaroxaban vs. Warfarin (Rivaroxaban), Optum Clinformatics - Rivaroxaban vs. Warfarin (Warfarin)
    Comments This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic- Apixaban vs. Warfarin (as reference group).
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.54
    Confidence Interval (2-Sided) 95%
    0.47 to 0.63
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    10. Secondary Outcome
    Title Major Gastrointestinal (GI) Bleeding
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Dabigatran vs. Warfarin (Dabigatran) Dabigatran vs. Warfarin (Warfarin) Rivaroxaban vs. Warfarin (Rivaroxaban) Rivaroxaban vs. Warfarin (Warfarin) Apixaban vs. Warfarin (Apixaban) Apixaban vs. Warfarin (Warfarin)
    Arm/Group Description 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 or MarketScan before treatment initiation and matched on propensity scores with 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 or MarketScan before treatment initiation and matched on propensity scores with dabigatran 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 or MarketScan before treatment initiation and matched on propensity scores with warfarin Patients with non- valvular atrial fibrillation (NVAF) and new initiators of warfarin, during July 2011 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 with rivaroxaban 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 or MarketScan before treatment initiation and matched on propensity scores with warfarin Patients with non- valvular atrial fibrillation (NVAF) and new initiators of warfarin, during January 2013 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 with apixaban
    Measure Participants 29448 29448 35520 35520 19588 19588
    Number (95% Confidence Interval) [Incidence rate per 100 person-years]
    2.39
    2.82
    3.82
    3.43
    1.99
    3.59
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Optum Clinformatics - Dabigatran vs. Warfarin (Dabigatran), Optum Clinformatics - Dabigatran vs. Warfarin (Warfarin)
    Comments This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic-Dabigatran vs. Warfarin (as reference group).
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.89
    Confidence Interval (2-Sided) 95%
    0.77 to 1.04
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection MarketScan - Dabigatran vs. Warfarin (Dabigatran), MarketScan - Dabigatran vs. Warfarin (Warfarin)
    Comments This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic- Rivaroxaban vs. Warfarin (as reference group).
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.21
    Confidence Interval (2-Sided) 95%
    1.07 to 1.36
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Optum Clinformatics - Rivaroxaban vs. Warfarin (Rivaroxaban), Optum Clinformatics - Rivaroxaban vs. Warfarin (Warfarin)
    Comments This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic- Apixaban vs. Warfarin (as reference group).
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.59
    Confidence Interval (2-Sided) 95%
    0.48 to 0.72
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    11. Secondary Outcome
    Title Major Upper Gastrointestinal Bleeding
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Dabigatran vs. Warfarin (Dabigatran) Dabigatran vs. Warfarin (Warfarin) Rivaroxaban vs. Warfarin (Rivaroxaban) Rivaroxaban vs. Warfarin (Warfarin) Apixaban vs. Warfarin (Apixaban) Apixaban vs. Warfarin (Warfarin)
    Arm/Group Description 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 or MarketScan before treatment initiation and matched on propensity scores with 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 or MarketScan before treatment initiation and matched on propensity scores with dabigatran 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 or MarketScan before treatment initiation and matched on propensity scores with warfarin Patients with non- valvular atrial fibrillation (NVAF) and new initiators of warfarin, during July 2011 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 with rivaroxaban 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 or MarketScan before treatment initiation and matched on propensity scores with warfarin Patients with non- valvular atrial fibrillation (NVAF) and new initiators of warfarin, during January 2013 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 with apixaban
    Measure Participants 29448 29448 35520 35520 19588 19588
    Number (95% Confidence Interval) [Incidence rate per 100 person-years]
    0.51
    0.90
    0.99
    0.88
    0.64
    0.89
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Optum Clinformatics - Dabigatran vs. Warfarin (Dabigatran), Optum Clinformatics - Dabigatran vs. Warfarin (Warfarin)
    Comments This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic-Dabigatran vs. Warfarin (as reference group).
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.60
    Confidence Interval (2-Sided) 95%
    0.44 to 0.80
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection MarketScan - Dabigatran vs. Warfarin (Dabigatran), MarketScan - Dabigatran vs. Warfarin (Warfarin)
    Comments This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic- Rivaroxaban vs. Warfarin (as reference group).
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.24
    Confidence Interval (2-Sided) 95%
    0.98 to 1.57
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Optum Clinformatics - Rivaroxaban vs. Warfarin (Rivaroxaban), Optum Clinformatics - Rivaroxaban vs. Warfarin (Warfarin)
    Comments This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic- Apixaban vs. Warfarin (as reference group).
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.79
    Confidence Interval (2-Sided) 95%
    0.54 to 1.14
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    12. Secondary Outcome
    Title Major Lower Gastrointestinal Bleeding
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Dabigatran vs. Warfarin (Dabigatran) Dabigatran vs. Warfarin (Warfarin) Rivaroxaban vs. Warfarin (Rivaroxaban) Rivaroxaban vs. Warfarin (Warfarin) Apixaban vs. Warfarin (Apixaban) Apixaban vs. Warfarin (Warfarin)
    Arm/Group Description 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 or MarketScan before treatment initiation and matched on propensity scores with 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 or MarketScan before treatment initiation and matched on propensity scores with dabigatran 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 or MarketScan before treatment initiation and matched on propensity scores with warfarin Patients with non- valvular atrial fibrillation (NVAF) and new initiators of warfarin, during July 2011 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 with rivaroxaban 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 or MarketScan before treatment initiation and matched on propensity scores with warfarin Patients with non- valvular atrial fibrillation (NVAF) and new initiators of warfarin, during January 2013 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 with apixaban
    Measure Participants 29448 29448 35520 35520 19588 19588
    Number (95% Confidence Interval) [Incidence rate per 100 person-years]
    2.18
    2.48
    3.40
    3.09
    1.61
    3.17
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Optum Clinformatics - Dabigatran vs. Warfarin (Dabigatran), Optum Clinformatics - Dabigatran vs. Warfarin (Warfarin)
    Comments This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic-Dabigatran vs. Warfarin (as reference group).
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.93
    Confidence Interval (2-Sided) 95%
    0.79 to 1.08
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection MarketScan - Dabigatran vs. Warfarin (Dabigatran), MarketScan - Dabigatran vs. Warfarin (Warfarin)
    Comments This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic- Rivaroxaban vs. Warfarin (as reference group).
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.19
    Confidence Interval (2-Sided) 95%
    1.05 to 1.35
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Optum Clinformatics - Rivaroxaban vs. Warfarin (Rivaroxaban), Optum Clinformatics - Rivaroxaban vs. Warfarin (Warfarin)
    Comments This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic- Apixaban vs. Warfarin (as reference group).
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.54
    Confidence Interval (2-Sided) 95%
    0.44 to 0.67
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    13. Secondary Outcome
    Title Major Urogenital Bleeding
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Dabigatran vs. Warfarin (Dabigatran) Dabigatran vs. Warfarin (Warfarin) Rivaroxaban vs. Warfarin (Rivaroxaban) Rivaroxaban vs. Warfarin (Warfarin) Apixaban vs. Warfarin (Apixaban) Apixaban vs. Warfarin (Warfarin)
    Arm/Group Description 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 or MarketScan before treatment initiation and matched on propensity scores with 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 or MarketScan before treatment initiation and matched on propensity scores with dabigatran 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 or MarketScan before treatment initiation and matched on propensity scores with warfarin Patients with non- valvular atrial fibrillation (NVAF) and new initiators of warfarin, during July 2011 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 with rivaroxaban 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 or MarketScan before treatment initiation and matched on propensity scores with warfarin Patients with non- valvular atrial fibrillation (NVAF) and new initiators of warfarin, during January 2013 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 with apixaban
    Measure Participants 29448 29448 35520 35520 19588 19588
    Number (95% Confidence Interval) [Incidence rate per 100 person-years]
    0.01
    0.00
    0.02
    0.00
    0.00
    0.00
    14. Secondary Outcome
    Title Other Major Bleeding
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Dabigatran vs. Warfarin (Dabigatran) Dabigatran vs. Warfarin (Warfarin) Rivaroxaban vs. Warfarin (Rivaroxaban) Rivaroxaban vs. Warfarin (Warfarin) Apixaban vs. Warfarin (Apixaban) Apixaban vs. Warfarin (Warfarin)
    Arm/Group Description 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 or MarketScan before treatment initiation and matched on propensity scores with 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 or MarketScan before treatment initiation and matched on propensity scores with dabigatran 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 or MarketScan before treatment initiation and matched on propensity scores with warfarin Patients with non- valvular atrial fibrillation (NVAF) and new initiators of warfarin, during July 2011 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 with rivaroxaban 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 or MarketScan before treatment initiation and matched on propensity scores with warfarin Patients with non- valvular atrial fibrillation (NVAF) and new initiators of warfarin, during January 2013 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 with apixaban
    Measure Participants 29448 29448 35520 35520 19588 19588
    Number (95% Confidence Interval) [Incidence rate per 100 person-years]
    2.32
    3.65
    4.33
    4.59
    2.54
    4.86
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Optum Clinformatics - Dabigatran vs. Warfarin (Dabigatran), Optum Clinformatics - Dabigatran vs. Warfarin (Warfarin)
    Comments This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic-Dabigatran vs. Warfarin (as reference group).
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.68
    Confidence Interval (2-Sided) 95%
    0.59 to 078
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection MarketScan - Dabigatran vs. Warfarin (Dabigatran), MarketScan - Dabigatran vs. Warfarin (Warfarin)
    Comments This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic- Rivaroxaban vs. Warfarin (as reference group).
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.04
    Confidence Interval (2-Sided) 95%
    0.93 to 1.16
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Optum Clinformatics - Rivaroxaban vs. Warfarin (Rivaroxaban), Optum Clinformatics - Rivaroxaban vs. Warfarin (Warfarin)
    Comments This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic- Apixaban vs. Warfarin (as reference group).
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.56
    Confidence Interval (2-Sided) 95%
    0.47 to 0.67
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    15. Secondary Outcome
    Title Transient Ischemic Attack (TIA)
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Dabigatran vs. Warfarin (Dabigatran) Dabigatran vs. Warfarin (Warfarin) Rivaroxaban vs. Warfarin (Rivaroxaban) Rivaroxaban vs. Warfarin (Warfarin) Apixaban vs. Warfarin (Apixaban) Apixaban vs. Warfarin (Warfarin)
    Arm/Group Description 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 or MarketScan before treatment initiation and matched on propensity scores with 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 or MarketScan before treatment initiation and matched on propensity scores with dabigatran 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 or MarketScan before treatment initiation and matched on propensity scores with warfarin Patients with non- valvular atrial fibrillation (NVAF) and new initiators of warfarin, during July 2011 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 with rivaroxaban 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 or MarketScan before treatment initiation and matched on propensity scores with warfarin Patients with non- valvular atrial fibrillation (NVAF) and new initiators of warfarin, during January 2013 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 with apixaban
    Measure Participants 29448 29448 35520 35520 19588 19588
    Number (95% Confidence Interval) [Incidence rate per 100 person-years]
    0.21
    0.43
    0.26
    0.31
    0.22
    0.32
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Optum Clinformatics - Dabigatran vs. Warfarin (Dabigatran), Optum Clinformatics - Dabigatran vs. Warfarin (Warfarin)
    Comments This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic-Dabigatran vs. Warfarin (as reference group).
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.53
    Confidence Interval (2-Sided) 95%
    0.34 to 0.82
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection MarketScan - Dabigatran vs. Warfarin (Dabigatran), MarketScan - Dabigatran vs. Warfarin (Warfarin)
    Comments This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic- Rivaroxaban vs. Warfarin (as reference group).
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.84
    Confidence Interval (2-Sided) 95%
    0.55 to 1.29
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Optum Clinformatics - Rivaroxaban vs. Warfarin (Rivaroxaban), Optum Clinformatics - Rivaroxaban vs. Warfarin (Warfarin)
    Comments This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic- Apixaban vs. Warfarin (as reference group).
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.76
    Confidence Interval (2-Sided) 95%
    0.41 to 1.42
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    16. Secondary Outcome
    Title Myocardial Infarction (MI)
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Dabigatran vs. Warfarin (Dabigatran) Dabigatran vs. Warfarin (Warfarin) Rivaroxaban vs. Warfarin (Rivaroxaban) Rivaroxaban vs. Warfarin (Warfarin) Apixaban vs. Warfarin (Apixaban) Apixaban vs. Warfarin (Warfarin)
    Arm/Group Description 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 or MarketScan before treatment initiation and matched on propensity scores with 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 or MarketScan before treatment initiation and matched on propensity scores with dabigatran 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 or MarketScan before treatment initiation and matched on propensity scores with warfarin Patients with non- valvular atrial fibrillation (NVAF) and new initiators of warfarin, during July 2011 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 with rivaroxaban 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 or MarketScan before treatment initiation and matched on propensity scores with warfarin Patients with non- valvular atrial fibrillation (NVAF) and new initiators of warfarin, during January 2013 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 with apixaban
    Measure Participants 29448 29448 35520 35520 19588 19588
    Number (95% Confidence Interval) [Incidence rate per 100 person-years]
    0.48
    0.60
    0.53
    0.65
    0.57
    0.74
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Optum Clinformatics - Dabigatran vs. Warfarin (Dabigatran), Optum Clinformatics - Dabigatran vs. Warfarin (Warfarin)
    Comments This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic-Dabigatran vs. Warfarin (as reference group).
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.83
    Confidence Interval (2-Sided) 95%
    0.60 to 1.15
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection MarketScan - Dabigatran vs. Warfarin (Dabigatran), MarketScan - Dabigatran vs. Warfarin (Warfarin)
    Comments This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic- Rivaroxaban vs. Warfarin (as reference group).
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.85
    Confidence Interval (2-Sided) 95%
    0.63 to 1.14
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Optum Clinformatics - Rivaroxaban vs. Warfarin (Rivaroxaban), Optum Clinformatics - Rivaroxaban vs. Warfarin (Warfarin)
    Comments This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic- Apixaban vs. Warfarin (as reference group).
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.79
    Confidence Interval (2-Sided) 95%
    0.53 to 1.18
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    17. Secondary Outcome
    Title Venous Thromboembolism (VTE)
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Dabigatran vs. Warfarin (Dabigatran) Dabigatran vs. Warfarin (Warfarin) Rivaroxaban vs. Warfarin (Rivaroxaban) Rivaroxaban vs. Warfarin (Warfarin) Apixaban vs. Warfarin (Apixaban) Apixaban vs. Warfarin (Warfarin)
    Arm/Group Description 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 or MarketScan before treatment initiation and matched on propensity scores with 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 or MarketScan before treatment initiation and matched on propensity scores with dabigatran 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 or MarketScan before treatment initiation and matched on propensity scores with warfarin Patients with non- valvular atrial fibrillation (NVAF) and new initiators of warfarin, during July 2011 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 with rivaroxaban 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 or MarketScan before treatment initiation and matched on propensity scores with warfarin Patients with non- valvular atrial fibrillation (NVAF) and new initiators of warfarin, during January 2013 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 with apixaban
    Measure Participants 29448 29448 35520 35520 19588 19588
    Number (95% Confidence Interval) [Incidence rate per 100 person-years]
    0.67
    1.14
    1.20
    1.65
    0.57
    1.21
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Optum Clinformatics - Dabigatran vs. Warfarin (Dabigatran), Optum Clinformatics - Dabigatran vs. Warfarin (Warfarin)
    Comments This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic-Dabigatran vs. Warfarin (as reference group).
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.65
    Confidence Interval (2-Sided) 95%
    0.50 to 0.84
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection MarketScan - Dabigatran vs. Warfarin (Dabigatran), MarketScan - Dabigatran vs. Warfarin (Warfarin)
    Comments This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic-Rivaroxaban vs. Warfarin (as reference group).
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.84
    Confidence Interval (2-Sided) 95%
    0.69 to 1.01
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Optum Clinformatics - Rivaroxaban vs. Warfarin (Rivaroxaban), Optum Clinformatics - Rivaroxaban vs. Warfarin (Warfarin)
    Comments This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic- Apixaban vs. Warfarin (as reference group).
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.53
    Confidence Interval (2-Sided) 95%
    0.37 to 0.76
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    18. Secondary Outcome
    Title Deep Vein Thrombosis (DVT)
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Dabigatran vs. Warfarin (Dabigatran) Dabigatran vs. Warfarin (Warfarin) Rivaroxaban vs. Warfarin (Rivaroxaban) Rivaroxaban vs. Warfarin (Warfarin) Apixaban vs. Warfarin (Apixaban) Apixaban vs. Warfarin (Warfarin)
    Arm/Group Description 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 or MarketScan before treatment initiation and matched on propensity scores with 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 or MarketScan before treatment initiation and matched on propensity scores with dabigatran 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 or MarketScan before treatment initiation and matched on propensity scores with warfarin Patients with non- valvular atrial fibrillation (NVAF) and new initiators of warfarin, during July 2011 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 with rivaroxaban 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 or MarketScan before treatment initiation and matched on propensity scores with warfarin Patients with non- valvular atrial fibrillation (NVAF) and new initiators of warfarin, during January 2013 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 with apixaban
    Measure Participants 29448 29448 35520 35520 19588 19588
    Number (95% Confidence Interval) [Incidence rate per 100 person-years]
    0.46
    0.78
    0.78
    1.09
    0.41
    0.75
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Optum Clinformatics - Dabigatran vs. Warfarin (Dabigatran), Optum Clinformatics - Dabigatran vs. Warfarin (Warfarin)
    Comments This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic-Dabigatran vs. Warfarin (as reference group).
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.65
    Confidence Interval (2-Sided) 95%
    0.47 to 0.88
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection MarketScan - Dabigatran vs. Warfarin (Dabigatran), MarketScan - Dabigatran vs. Warfarin (Warfarin)
    Comments This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic- Rivaroxaban vs. Warfarin (as reference group).
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.82
    Confidence Interval (2-Sided) 95%
    0.65 to 1.04
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Optum Clinformatics - Rivaroxaban vs. Warfarin (Rivaroxaban), Optum Clinformatics - Rivaroxaban vs. Warfarin (Warfarin)
    Comments This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic- Apixaban vs. Warfarin (as reference group).
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.60
    Confidence Interval (2-Sided) 95%
    0.39 to 0.92
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    19. Secondary Outcome
    Title Pulmonary Embolism (PE)
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Dabigatran vs. Warfarin (Dabigatran) Dabigatran vs. Warfarin (Warfarin) Rivaroxaban vs. Warfarin (Rivaroxaban) Rivaroxaban vs. Warfarin (Warfarin) Apixaban vs. Warfarin (Apixaban) Apixaban vs. Warfarin (Warfarin)
    Arm/Group Description 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 or MarketScan before treatment initiation and matched on propensity scores with 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 or MarketScan before treatment initiation and matched on propensity scores with dabigatran 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 or MarketScan before treatment initiation and matched on propensity scores with warfarin Patients with non- valvular atrial fibrillation (NVAF) and new initiators of warfarin, during July 2011 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 with rivaroxaban 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 or MarketScan before treatment initiation and matched on propensity scores with warfarin Patients with non- valvular atrial fibrillation (NVAF) and new initiators of warfarin, during January 2013 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 with apixaban
    Measure Participants 29448 29448 35520 35520 19588 19588
    Number (95% Confidence Interval) [Incidence rate per 100 person-years]
    0.29
    0.46
    0.54
    0.81
    0.22
    0.62
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Optum Clinformatics - Dabigatran vs. Warfarin (Dabigatran), Optum Clinformatics - Dabigatran vs. Warfarin (Warfarin)
    Comments This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic- Dabigatran vs. Warfarin (as reference group).
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.70
    Confidence Interval (2-Sided) 95%
    0.47 to 1.04
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection MarketScan - Dabigatran vs. Warfarin (Dabigatran), MarketScan - Dabigatran vs. Warfarin (Warfarin)
    Comments This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic- Rivaroxaban vs. Warfarin (as reference group).
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.79
    Confidence Interval (2-Sided) 95%
    0.60 to 1.05
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Optum Clinformatics - Rivaroxaban vs. Warfarin (Rivaroxaban), Optum Clinformatics - Rivaroxaban vs. Warfarin (Warfarin)
    Comments This is a pooled analysis involving data from both MarketScan and Optum databases. MarketScan and Optum Clinformatic- Apixaban vs. Warfarin (as reference group).
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.42
    Confidence Interval (2-Sided) 95%
    0.24 to 0.73
    Parameter Dispersion Type:
    Value:
    Estimation Comments

    Adverse Events

    Time Frame Individual safety reporting was not applicable for this study
    Adverse Event Reporting Description This was an observational study based on existing data (secondary data use); all patient data are de-identified and analyzed in aggregate. Individual patient safety related information was not captured during this study; therefore the individual safety reporting was not applicable for this study.
    Arm/Group Title Optum Clinformatics - Dabigatran Optum Clinformatics - Warfarin Optum Clinformatics - Rivaroxaban Optum Clinformatics - Apixaban MarketScan - Dabigatran MarketScan - Warfarin MarketScan - Rivaroxaban MarketScan - Apixaban
    Arm/Group Description 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 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 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 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 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 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 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 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
    All Cause Mortality
    Optum Clinformatics - Dabigatran Optum Clinformatics - Warfarin Optum Clinformatics - Rivaroxaban Optum Clinformatics - Apixaban MarketScan - Dabigatran MarketScan - Warfarin MarketScan - Rivaroxaban MarketScan - Apixaban
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/0 (NaN) 0/0 (NaN) 0/0 (NaN) 0/0 (NaN) 0/0 (NaN) 0/0 (NaN) 0/0 (NaN) 0/0 (NaN)
    Serious Adverse Events
    Optum Clinformatics - Dabigatran Optum Clinformatics - Warfarin Optum Clinformatics - Rivaroxaban Optum Clinformatics - Apixaban MarketScan - Dabigatran MarketScan - Warfarin MarketScan - Rivaroxaban MarketScan - Apixaban
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/0 (NaN) 0/0 (NaN) 0/0 (NaN) 0/0 (NaN) 0/0 (NaN) 0/0 (NaN) 0/0 (NaN) 0/0 (NaN)
    Other (Not Including Serious) Adverse Events
    Optum Clinformatics - Dabigatran Optum Clinformatics - Warfarin Optum Clinformatics - Rivaroxaban Optum Clinformatics - Apixaban MarketScan - Dabigatran MarketScan - Warfarin MarketScan - Rivaroxaban MarketScan - Apixaban
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/0 (NaN) 0/0 (NaN) 0/0 (NaN) 0/0 (NaN) 0/0 (NaN) 0/0 (NaN) 0/0 (NaN) 0/0 (NaN)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.

    Results Point of Contact

    Name/Title Boehringer Ingelheim, Call Center
    Organization Boehringer Ingelheim
    Phone 1-800-243-0127
    Email clintriage.rdg@boehringer-ingelheim.com
    Responsible Party:
    Boehringer Ingelheim
    ClinicalTrials.gov Identifier:
    NCT02081807
    Other Study ID Numbers:
    • 1160.207
    First Posted:
    Mar 7, 2014
    Last Update Posted:
    Oct 2, 2019
    Last Verified:
    Sep 1, 2019