Anticoagulants, Atrial Fibrillation, Obesity
Conditions
Keywords
Medicare, Veterans Affairs, Major Bleeding, Stroke
Brief summary
The overall objective of this analysis is to understand patient characteristics, the use of treatment, and clinical outcomes among obese (overweight) and severely obese patients with non-valvular atrial fibrillation (NVAF) who initiate therapy with OACs (oral anti-coagulants). The aim of this study is to compare all DOACs (direct oral anti-coagulants) to warfarin. However, the primary analysis will be conducted among apixaban vs warfarin patients only. If sample size permits, we will also conduct other DOAC vs warfarin and DOAC vs DOAC analysis.
Interventions
DRUGApixaban
Anticoagulant medication used to treat and prevent blood clots and to prevent stroke in people with nonvalvular atrial fibrillation.
Sponsors
Pfizer
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Obese or severely obese. * Initiated an OAC from July 1, 2013 - December 31, 2017; the first DOAC pharmacy claim date during the identification period will be designated as the index date. The first warfarin prescription date will be designated as the index date for patients without any DOAC claim. * Individuals ≥18 years old as of the index date. * Had 6 months continuous health plan enrollment with medical benefits (Parts A & B) for at least 6 months pre-index date (baseline period). * At least 1 diagnosis of AF prior to or on index date, identified by any medical claim associated with an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code of 427.31 or International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) code of I480-I482, and I4891. * Had body weight or BMI value reported within ±6 months of the index date.
Exclusion criteria
* Had medical claims indicating a diagnosis or procedure of rheumatic mitral valvular heart disease, heart valve replacement/transplant, venous thromboembolism, or transient AF 6 months prior to or on the index date. * Had hip/knee replacement surgery within 6 weeks prior to or on the index date. * Were pregnant during the study period. * Had an OAC prescription during the 6 months pre-index date. * Had follow-up time equal to 0 days. * Had more than one OAC on the index date.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Event Rate Per 100 Participant-Years For First Occurrence of Major Bleeding Events After Index Date in Obese Participants | From first dose of study drug to follow-up period or within 30 days from last prescription date (data collected and observed retrospectively for 3.5 years) | Event rate per 100 participant-years for first occurrence of major bleeding (MB) event after index date in obese participants was reported. MB after index date was identified using hospital claims and occurred anytime during the follow-up period of drug use or within 30 days from the last day of treatment prescription. Index date was defined as date of first DOAC pharmacy claim date during the identification period (July 1, 2013-December 31, 2017 \[3.5 years\]). The first warfarin prescription date was designated as the index date for participants without any DOAC claim. MB events included the composite of gastrointestinal (GI), intracranial hemorrhage (ICH), and other sites. MB was equal to 1 if bleeding event was greater than equal to (\>=) 1. |
| Event Rate Per 100 Participant-Years For First Occurrence of Major Bleeding Events After Index Date in Morbidly Obese Participants | From first dose of study drug to follow-up period or within 30 days from last prescription date (data collected and observed retrospectively for 3.5 years) | Event rate per 100 participant-years for first occurrence of MB event after index date in morbidly obese participants was reported. MB after index date was identified using hospital claims and occurred anytime during the follow-up period of drug use or within 30 days from the last day of treatment prescription. Index date was defined as date of first DOAC pharmacy claim date during the identification period (July 1, 2013-December 31, 2017). The first warfarin prescription date was designated as the index date for participants without any DOAC claim. MB events included the composite of GI, ICH, and other sites. MB was equal to 1 if bleeding event was \>=1. |
| Event Rate Per 100 Participant-Years For First Occurrence of Stroke or Systemic Embolism (SE) Events After Index Date in Obese Participants | From first dose of study drug to follow-up period or within 30 days from last prescription date (data collected and observed retrospectively for 3.5 years) | Event rate per 100 participant-years for first occurrence of stroke or SE events after index date in obese participants was reported. Stroke/SE were identified using hospital claims and occurred anytime during the period of drug use or within 30 days from the last day of treatment prescription. Index date was defined as date of first DOAC pharmacy claim date during the identification period (July 1, 2013-December 31, 2017). The first warfarin prescription date was designated as the index date for participants without any DOAC claim. Stroke events included the composite of any ischemic, any hemorrhagic and SE stroke events. Stroke/SE was equal to 1 if stroke event was \>=1. |
| Event Rate Per 100 Participant-Years For First Occurrence of Stroke or Systemic Embolism (SE) Events After Index Date in Morbidly Obese Participants | From first dose of study drug to follow-up period or within 30 days from last prescription date (data collected and observed retrospectively for 3.5 years) | Event rate per 100 participant-years for first occurrence of stroke or SE events after index date in morbidly obese participants was reported. Stroke/SE were identified using hospital claims and occurred anytime during the period of drug use or within 30 days from the last day of treatment prescription. Index date was defined as date of first DOAC pharmacy claim date during the identification period (July 1, 2013-December 31, 2017). The first warfarin prescription date was designated as the index date for participants without any DOAC claim. Stroke events included the composite of any ischemic, any hemorrhagic and SE stroke events. Stroke/SE was equal to 1 if stroke event was \>=1. |
| Event Rate Per 100 Participant-Years For First Occurrence of Net Clinical Benefit After Index Date in Obese Participants | From first dose of study drug to follow-up period or within 30 days from last prescription date (data collected and observed retrospectively for 3.5 years) | Event rate per 100 participant-years for first occurrence of net clinical benefit after index date in obese participants was reported. For participants with stroke/SE or MB event, net clinical benefit was assessed by evaluating the first hospital claim for a stroke/SE or MB event. The hospital claim occurred anytime during the period of drug use or within 30 days from the last day of supply of treatment prescription. Index date was defined as date of first DOAC pharmacy claim date during the identification period (July 1, 2013-December 31, 2017). The first warfarin prescription date was designated as the index date for participants without any DOAC claim. |
| Event Rate Per 100 Participant-Years For First Occurrence of Net Clinical Benefit After Index Date in Morbidly Obese Participants | From first dose of study drug to follow-up period or within 30 days from last prescription date (data collected and observed retrospectively for 3.5 years) | Event rate per 100 participant-years for first occurrence of net clinical benefit after index date in morbidly obese participants was reported. For participants with stroke/SE or MB event, net clinical benefit was assessed by evaluating the first hospital claim for a stroke/SE or MB event. The hospital claim occurred anytime during the period of drug use or within 30 days from the last day of supply of treatment prescription. Index date was defined as date of first DOAC pharmacy claim date during the identification period (July 1, 2013-December 31, 2017). The first warfarin prescription date was designated as the index date for participants without any DOAC claim. |
| Charlson Comorbidity Index (CCI) | Baseline (6 months prior to index date) | CCI based on various comorbid conditions such as myocardial infarction, CHF, peripheral vascular disease, cerebrovascular disease, dementia, chronic obstructive pulmonary disease, rheumatologic disease, peptic ulcer disease, mild liver disease, diabetes (mild to moderate), diabetes + complications, hemiplegia or paraplegia, renal disease, any malignancy (lymphoma and leukemia), moderate/severe liver disease, metastatic solid tumor, and acquired immune deficiency syndrome (AIDS) were reported. CCI score range was from 0 to 14, where 0= low comorbid condition and 14= high comorbid condition, higher scores indicated more comorbidity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time in Therapeutic Range (TTR) During Follow-up Period | From first dose of study drug to follow-up period or within 30 days from last prescription date (data collected and observed retrospectively for 3.5 years) | TTR was computed using INR values among warfarin participants during the follow-up. TTR was calculated based on the percentage of time a participant remained in therapeutic range evaluated during the entire follow-up period. TTR \>=65 percent (%) was observed as good and TTR less than (\<) 65% was observed as poor. |
Countries
United States
Participant flow
Recruitment details
This was a retrospective population-based registry study. Data for participants diagnosed with non-valvular atrial fibrillation (NVAF) and treated with either oral anticoagulants (OAC \[Warfarin\]) or direct oral anticoagulants (DOAC \[Apixaban, Dabigatran and Rivaroxaban\]) retrieved from the Veterans Affairs (VA) Population and Centre for Medicare and Medicare Services (CMS) database from January 2013 to December 2017.
Pre-assignment details
In this study, inverse probability of treatment weighted (IPTW) method was used in analysis of outcome measures to balance participant's characteristics among reporting groups. Baseline for this study was 6 months prior to the index date. The index date was the date of first prescription for an OAC (Warfarin) or DOAC (Apixaban, Dabigatran, and Rivaroxaban) pharmacy claim during the identification period from July 1, 2013 -December 31, 2017.
Participants by arm
| Arm | Count |
|---|---|
| Warfarin Participants diagnosed with NVAF, who initiated warfarin on the index date, were included in this cohort and their data from July 2013 to December 2017, available in VA and CMS database observed retrospectively. Index date was defined as the date of the first warfarin prescription for participants without any DOAC claim. | 35,051 |
| Apixaban Participants diagnosed with NVAF, who initiated apixaban on the index date, were included in this cohort and their data from July 2013 to December 2017, available in VA and CMS database observed retrospectively. Index date was defined as the date of the first DOAC pharmacy claim date during the identification period (July 1, 2013-December 31, 2017). | 38,756 |
| Dabigatran Participants diagnosed with NVAF, who initiated dabigatran on the index date, were included in this cohort and their data from July 2013 to December 2017, available in VA and CMS database observed retrospectively. Index date was defined as the date of the first DOAC pharmacy claim date during the identification period (July 1, 2013-December 31, 2017). | 12,148 |
| Rivaroxaban Participants diagnosed with NVAF, who initiated rivaroxaban on the index date, were included in this cohort and their data from July 2013 to December 2017, available in VA and CMS database observed retrospectively. Index date was defined as the date of the first DOAC pharmacy claim date during the identification period (July 1, 2013-December 31, 2017). | 21,428 |
| Total | 107,383 |
Baseline characteristics
| Characteristic | Warfarin | Apixaban | Dabigatran | Rivaroxaban | Total |
|---|---|---|---|---|---|
| Age, Customized 18-54 years | 182 Participants | 94 Participants | 88 Participants | 105 Participants | 469 Participants |
| Age, Customized 55-64 years | 1380 Participants | 833 Participants | 580 Participants | 827 Participants | 3620 Participants |
| Age, Customized 65-74 years | 12410 Participants | 13037 Participants | 6873 Participants | 10070 Participants | 42390 Participants |
| Age, Customized 75-79 years | 5817 Participants | 6504 Participants | 1741 Participants | 3472 Participants | 17534 Participants |
| Age, Customized >=80 years | 15262 Participants | 18288 Participants | 2866 Participants | 6954 Participants | 43370 Participants |
| Bariatric Surgery | 130 Participants | 125 Participants | 43 Participants | 93 Participants | 391 Participants |
| Baseline Medication Use ACE/ARB | 13562 Participants | 14295 Participants | 4777 Participants | 8049 Participants | 40683 Participants |
| Baseline Medication Use Anti-platelets | 8686 Participants | 10515 Participants | 2980 Participants | 5141 Participants | 27322 Participants |
| Baseline Medication Use Beta blockers | 18486 Participants | 20198 Participants | 6177 Participants | 11211 Participants | 56072 Participants |
| Baseline Medication Use H2-receptor antagonist | 2268 Participants | 2584 Participants | 695 Participants | 1288 Participants | 6835 Participants |
| Baseline Medication Use NSAIDS | 3819 Participants | 5319 Participants | 1904 Participants | 3388 Participants | 14430 Participants |
| Baseline Medication Use Proton pump inhibitor | 12227 Participants | 13793 Participants | 3896 Participants | 7178 Participants | 37094 Participants |
| Baseline Medication Use Statins | 23095 Participants | 25830 Participants | 7959 Participants | 13901 Participants | 70785 Participants |
| Body Mass Index (BMI) (18.5-24.9) kg/m^2 | 5921 Participants | 6890 Participants | 1586 Participants | 3158 Participants | 17555 Participants |
| Body Mass Index (BMI) <18.5 kg/m^2 | 285 Participants | 296 Participants | 47 Participants | 121 Participants | 749 Participants |
| Body Mass Index (BMI) (25-29) kg/m^2 | 8803 Participants | 10490 Participants | 3041 Participants | 5563 Participants | 27897 Participants |
| Body Mass Index (BMI) (30-39) kg/m^2 | 10293 Participants | 11425 Participants | 4357 Participants | 6923 Participants | 32998 Participants |
| Body Mass Index (BMI) >40 kg/m^2 | 2176 Participants | 1746 Participants | 896 Participants | 1294 Participants | 6112 Participants |
| Body Mass Index (BMI) Missing | 7573 Participants | 7909 Participants | 2221 Participants | 4369 Participants | 22072 Participants |
| Body Weight 100-119 Kg | 7102 Participants | 7830 Participants | 3094 Participants | 4776 Participants | 22802 Participants |
| Body Weight >=120 Kg | 3714 Participants | 3261 Participants | 1614 Participants | 2478 Participants | 11067 Participants |
| Body Weight <=60 Kg | 871 Participants | 1009 Participants | 149 Participants | 359 Participants | 2388 Participants |
| Body Weight 61-99 Kg | 22449 Participants | 25698 Participants | 6924 Participants | 13225 Participants | 68296 Participants |
| Body Weight Missing | 915 Participants | 958 Participants | 367 Participants | 590 Participants | 2830 Participants |
| CHA2DS2-VASc Score 0 | 79 Participants | 70 Participants | 71 Participants | 87 Participants | 307 Participants |
| CHA2DS2-VASc Score 1 | 1280 Participants | 1405 Participants | 886 Participants | 1227 Participants | 4798 Participants |
| CHA2DS2-VASc Score 2 | 4703 Participants | 5764 Participants | 2709 Participants | 4007 Participants | 17183 Participants |
| CHA2DS2-VASc Score 3 | 8196 Participants | 9734 Participants | 3520 Participants | 5718 Participants | 27168 Participants |
| CHA2DS2-VASc Score >=4 | 20793 Participants | 21783 Participants | 4962 Participants | 10389 Participants | 57927 Participants |
| CHADS2 Score 0 | 1424 Participants | 1506 Participants | 944 Participants | 1352 Participants | 5226 Participants |
| CHADS2 Score 1 | 6829 Participants | 7280 Participants | 3640 Participants | 5413 Participants | 23162 Participants |
| CHADS2 Score 2 | 11372 Participants | 12318 Participants | 3985 Participants | 6935 Participants | 34610 Participants |
| CHADS2 Score >=3 | 15426 Participants | 17652 Participants | 3579 Participants | 7728 Participants | 44385 Participants |
| Comorbid Conditions Alcoholism | 11323 Participants | 14181 Participants | 4241 Participants | 7567 Participants | 37312 Participants |
| Comorbid Conditions Anemia and Coagulation Defects | 10572 Participants | 9987 Participants | 2129 Participants | 4640 Participants | 27328 Participants |
| Comorbid Conditions Bleeding History | 6021 Participants | 5564 Participants | 1367 Participants | 2886 Participants | 15838 Participants |
| Comorbid Conditions CHF | 13188 Participants | 12385 Participants | 3025 Participants | 6062 Participants | 34660 Participants |
| Comorbid Conditions Coronary Artery Disease | 19283 Participants | 21041 Participants | 5664 Participants | 10903 Participants | 56891 Participants |
| Comorbid Conditions Diabetes Mellitus | 15527 Participants | 15225 Participants | 4714 Participants | 8453 Participants | 43919 Participants |
| Comorbid Conditions Dyspepsia or Stomach Discomfort | 4322 Participants | 4201 Participants | 1110 Participants | 2438 Participants | 12071 Participants |
| Comorbid Conditions Hypertension | 29689 Participants | 32639 Participants | 10117 Participants | 17961 Participants | 90406 Participants |
| Comorbid Conditions Liver Disease | 1430 Participants | 1388 Participants | 418 Participants | 814 Participants | 4050 Participants |
| Comorbid Conditions Myocardial Infarction | 5344 Participants | 5628 Participants | 1200 Participants | 2841 Participants | 15013 Participants |
| Comorbid Conditions Non-stroke/SE Peripheral Vascular Disease | 8994 Participants | 9560 Participants | 2276 Participants | 4836 Participants | 25666 Participants |
| Comorbid Conditions Peripheral Artery Disease | 8817 Participants | 8927 Participants | 2156 Participants | 4610 Participants | 24510 Participants |
| Comorbid Conditions Renal Disease | 4540 Participants | 8022 Participants | 929 Participants | 2367 Participants | 15858 Participants |
| Comorbid Conditions Stroke/SE | 4468 Participants | 4731 Participants | 1062 Participants | 2186 Participants | 12447 Participants |
| Comorbid Conditions TIA | 2750 Participants | 4508 Participants | 840 Participants | 1807 Participants | 9905 Participants |
| Dose of the Index DOAC Lower Dose (2.5 mg Apixaban, 75 mg Dabigatran, 15 mg Rivaroxaban) | 0 Participants | 8262 Participants | 726 Participants | 4550 Participants | 13538 Participants |
| Dose of the Index DOAC Other Dose (10 mg Rivaroxaban , 110 mg Dabigatran) | 0 Participants | 0 Participants | 11 Participants | 770 Participants | 781 Participants |
| Dose of the Index DOAC Standard Dose (5 mg Apixaban, 150 mg Dabigatran, 20 mg Rivaroxaban) | 0 Participants | 30494 Participants | 11411 Participants | 16108 Participants | 58013 Participants |
| HAS-BLED Score 0 | 135 Participants | 109 Participants | 83 Participants | 130 Participants | 457 Participants |
| HAS-BLED Score 1 | 3859 Participants | 4522 Participants | 1733 Participants | 2770 Participants | 12884 Participants |
| HAS-BLED Score 2 | 11444 Participants | 13675 Participants | 5457 Participants | 8533 Participants | 39109 Participants |
| HAS-BLED Score >=3 | 19613 Participants | 20450 Participants | 4875 Participants | 9995 Participants | 54933 Participants |
| International Normalized Ratio (INR) No | 19747 Participants | 29623 Participants | 8587 Participants | 17451 Participants | 75408 Participants |
| International Normalized Ratio (INR) Yes | 15304 Participants | 9133 Participants | 3561 Participants | 3977 Participants | 31975 Participants |
| Number of Participants Classified According to OAC Index Year 2013 | 5090 Participants | 395 Participants | 974 Participants | 1135 Participants | 7594 Participants |
| Number of Participants Classified According to OAC Index Year 2014 | 9024 Participants | 2548 Participants | 2462 Participants | 3996 Participants | 18030 Participants |
| Number of Participants Classified According to OAC Index Year 2015 | 7770 Participants | 6792 Participants | 2178 Participants | 4370 Participants | 21110 Participants |
| Number of Participants Classified According to OAC Index Year 2016 | 7289 Participants | 12705 Participants | 3336 Participants | 5600 Participants | 28930 Participants |
| Number of Participants Classified According to OAC Index Year 2017 | 5878 Participants | 16316 Participants | 3198 Participants | 6327 Participants | 31719 Participants |
| Number of Participants From Different Regions of United States Midwest | 10498 Participants | 10046 Participants | 3008 Participants | 5858 Participants | 29410 Participants |
| Number of Participants From Different Regions of United States Northeast | 7016 Participants | 6821 Participants | 1887 Participants | 3718 Participants | 19442 Participants |
| Number of Participants From Different Regions of United States Other/Unknown | 152 Participants | 186 Participants | 39 Participants | 93 Participants | 470 Participants |
| Number of Participants From Different Regions of United States South | 11809 Participants | 15311 Participants | 5080 Participants | 8398 Participants | 40598 Participants |
| Number of Participants From Different Regions of United States West | 5576 Participants | 6392 Participants | 2134 Participants | 3361 Participants | 17463 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2086 Participants | 2024 Participants | 621 Participants | 1172 Participants | 5903 Participants |
| Race (NIH/OMB) More than one race | 529 Participants | 654 Participants | 220 Participants | 343 Participants | 1746 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 190 Participants | 231 Participants | 123 Participants | 181 Participants | 725 Participants |
| Race (NIH/OMB) White | 32246 Participants | 35847 Participants | 11184 Participants | 19732 Participants | 99009 Participants |
| Sex: Female, Male Female | 456 Participants | 576 Participants | 139 Participants | 299 Participants | 1470 Participants |
| Sex: Female, Male Male | 34595 Participants | 38180 Participants | 12009 Participants | 21129 Participants | 105913 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 |
Outcome results
Primary
Charlson Comorbidity Index (CCI)
CCI based on various comorbid conditions such as myocardial infarction, CHF, peripheral vascular disease, cerebrovascular disease, dementia, chronic obstructive pulmonary disease, rheumatologic disease, peptic ulcer disease, mild liver disease, diabetes (mild to moderate), diabetes + complications, hemiplegia or paraplegia, renal disease, any malignancy (lymphoma and leukemia), moderate/severe liver disease, metastatic solid tumor, and acquired immune deficiency syndrome (AIDS) were reported. CCI score range was from 0 to 14, where 0= low comorbid condition and 14= high comorbid condition, higher scores indicated more comorbidity.
Time frame: Baseline (6 months prior to index date)
Population: Analysis population included obese or morbidly obese AF participants in the CMS and VA databases with newly prescribed OACs or DOACs between January 1, 2013 and December 31, 2017.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Warfarin | Charlson Comorbidity Index (CCI) | 3.13 Units on a scale | Standard Deviation 2.68 |
| Apixaban | Charlson Comorbidity Index (CCI) | 2.55 Units on a scale | Standard Deviation 2.39 |
| Dabigatran | Charlson Comorbidity Index (CCI) | 2.21 Units on a scale | Standard Deviation 2.18 |
| Rivaroxaban | Charlson Comorbidity Index (CCI) | 2.49 Units on a scale | Standard Deviation 2.37 |
Primary
Event Rate Per 100 Participant-Years For First Occurrence of Major Bleeding Events After Index Date in Morbidly Obese Participants
Event rate per 100 participant-years for first occurrence of MB event after index date in morbidly obese participants was reported. MB after index date was identified using hospital claims and occurred anytime during the follow-up period of drug use or within 30 days from the last day of treatment prescription. Index date was defined as date of first DOAC pharmacy claim date during the identification period (July 1, 2013-December 31, 2017). The first warfarin prescription date was designated as the index date for participants without any DOAC claim. MB events included the composite of GI, ICH, and other sites. MB was equal to 1 if bleeding event was \>=1.
Time frame: From first dose of study drug to follow-up period or within 30 days from last prescription date (data collected and observed retrospectively for 3.5 years)
Population: Morbidly obese participants with or without DOAC treatment diagnosed with NVAF were included in the outcome measure. Analysis performed using IPTW method to balance participant characteristics among reporting groups.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Warfarin | Event Rate Per 100 Participant-Years For First Occurrence of Major Bleeding Events After Index Date in Morbidly Obese Participants | 5.52 Events Per 100 Participant-Years |
| Apixaban | Event Rate Per 100 Participant-Years For First Occurrence of Major Bleeding Events After Index Date in Morbidly Obese Participants | 3.94 Events Per 100 Participant-Years |
Primary
Event Rate Per 100 Participant-Years For First Occurrence of Major Bleeding Events After Index Date in Obese Participants
Event rate per 100 participant-years for first occurrence of major bleeding (MB) event after index date in obese participants was reported. MB after index date was identified using hospital claims and occurred anytime during the follow-up period of drug use or within 30 days from the last day of treatment prescription. Index date was defined as date of first DOAC pharmacy claim date during the identification period (July 1, 2013-December 31, 2017 \[3.5 years\]). The first warfarin prescription date was designated as the index date for participants without any DOAC claim. MB events included the composite of gastrointestinal (GI), intracranial hemorrhage (ICH), and other sites. MB was equal to 1 if bleeding event was greater than equal to (\>=) 1.
Time frame: From first dose of study drug to follow-up period or within 30 days from last prescription date (data collected and observed retrospectively for 3.5 years)
Population: Obese participants with or without DOAC treatment diagnosed with NVAF were included in the outcome measure. Analysis performed using IPTW method to balance participant characteristics among reporting groups.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Warfarin | Event Rate Per 100 Participant-Years For First Occurrence of Major Bleeding Events After Index Date in Obese Participants | 7.27 Events Per 100 Participant-Years |
| Apixaban | Event Rate Per 100 Participant-Years For First Occurrence of Major Bleeding Events After Index Date in Obese Participants | 4.06 Events Per 100 Participant-Years |
Comparison: Cox Proportional Hazards Model was used to compare the risk of MB between cohorts.p-value: <0.00195% CI: [0.54, 0.7]Cox Proportional Hazards Model
Primary
Event Rate Per 100 Participant-Years For First Occurrence of Net Clinical Benefit After Index Date in Morbidly Obese Participants
Event rate per 100 participant-years for first occurrence of net clinical benefit after index date in morbidly obese participants was reported. For participants with stroke/SE or MB event, net clinical benefit was assessed by evaluating the first hospital claim for a stroke/SE or MB event. The hospital claim occurred anytime during the period of drug use or within 30 days from the last day of supply of treatment prescription. Index date was defined as date of first DOAC pharmacy claim date during the identification period (July 1, 2013-December 31, 2017). The first warfarin prescription date was designated as the index date for participants without any DOAC claim.
Time frame: From first dose of study drug to follow-up period or within 30 days from last prescription date (data collected and observed retrospectively for 3.5 years)
Population: Morbidly obese participants with or without DOAC treatment diagnosed with NVAF were included in this outcome measure. Analysis performed using IPTW method to balance participant characteristics among reporting groups.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Warfarin | Event Rate Per 100 Participant-Years For First Occurrence of Net Clinical Benefit After Index Date in Morbidly Obese Participants | 6.48 Event Rate Per 100 Participant-Years |
| Apixaban | Event Rate Per 100 Participant-Years For First Occurrence of Net Clinical Benefit After Index Date in Morbidly Obese Participants | 4.52 Event Rate Per 100 Participant-Years |
Primary
Event Rate Per 100 Participant-Years For First Occurrence of Net Clinical Benefit After Index Date in Obese Participants
Event rate per 100 participant-years for first occurrence of net clinical benefit after index date in obese participants was reported. For participants with stroke/SE or MB event, net clinical benefit was assessed by evaluating the first hospital claim for a stroke/SE or MB event. The hospital claim occurred anytime during the period of drug use or within 30 days from the last day of supply of treatment prescription. Index date was defined as date of first DOAC pharmacy claim date during the identification period (July 1, 2013-December 31, 2017). The first warfarin prescription date was designated as the index date for participants without any DOAC claim.
Time frame: From first dose of study drug to follow-up period or within 30 days from last prescription date (data collected and observed retrospectively for 3.5 years)
Population: Obese participants with or without DOAC treatment diagnosed with NVAF were included in this outcome measure. Analysis performed using IPTW method to balance participant characteristics among reporting groups.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Warfarin | Event Rate Per 100 Participant-Years For First Occurrence of Net Clinical Benefit After Index Date in Obese Participants | 8.44 Event Rate Per 100 Participant-Years |
| Apixaban | Event Rate Per 100 Participant-Years For First Occurrence of Net Clinical Benefit After Index Date in Obese Participants | 5.12 Event Rate Per 100 Participant-Years |
Comparison: Cox Proportional Hazards Model was used to compare the risk of net clinical benefit between cohorts.p-value: <0.00195% CI: [0.6, 0.76]Cox Proportional Hazards Model
Primary
Event Rate Per 100 Participant-Years For First Occurrence of Stroke or Systemic Embolism (SE) Events After Index Date in Morbidly Obese Participants
Event rate per 100 participant-years for first occurrence of stroke or SE events after index date in morbidly obese participants was reported. Stroke/SE were identified using hospital claims and occurred anytime during the period of drug use or within 30 days from the last day of treatment prescription. Index date was defined as date of first DOAC pharmacy claim date during the identification period (July 1, 2013-December 31, 2017). The first warfarin prescription date was designated as the index date for participants without any DOAC claim. Stroke events included the composite of any ischemic, any hemorrhagic and SE stroke events. Stroke/SE was equal to 1 if stroke event was \>=1.
Time frame: From first dose of study drug to follow-up period or within 30 days from last prescription date (data collected and observed retrospectively for 3.5 years)
Population: Morbidly obese participants with or without DOAC treatment diagnosed with NVAF were included in this outcome measure. Analysis performed using IPTW method to balance participant characteristics among reporting groups.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Warfarin | Event Rate Per 100 Participant-Years For First Occurrence of Stroke or Systemic Embolism (SE) Events After Index Date in Morbidly Obese Participants | 1.51 Events Per 100 Participant-Years |
| Apixaban | Event Rate Per 100 Participant-Years For First Occurrence of Stroke or Systemic Embolism (SE) Events After Index Date in Morbidly Obese Participants | 0.92 Events Per 100 Participant-Years |
Primary
Event Rate Per 100 Participant-Years For First Occurrence of Stroke or Systemic Embolism (SE) Events After Index Date in Obese Participants
Event rate per 100 participant-years for first occurrence of stroke or SE events after index date in obese participants was reported. Stroke/SE were identified using hospital claims and occurred anytime during the period of drug use or within 30 days from the last day of treatment prescription. Index date was defined as date of first DOAC pharmacy claim date during the identification period (July 1, 2013-December 31, 2017). The first warfarin prescription date was designated as the index date for participants without any DOAC claim. Stroke events included the composite of any ischemic, any hemorrhagic and SE stroke events. Stroke/SE was equal to 1 if stroke event was \>=1.
Time frame: From first dose of study drug to follow-up period or within 30 days from last prescription date (data collected and observed retrospectively for 3.5 years)
Population: Obese participants with or without DOAC treatment diagnosed with NVAF were included in this outcome measure. Analysis performed using IPTW method to balance participant characteristics among reporting groups.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Warfarin | Event Rate Per 100 Participant-Years For First Occurrence of Stroke or Systemic Embolism (SE) Events After Index Date in Obese Participants | 2.09 Events Per 100 Participant-Years |
| Apixaban | Event Rate Per 100 Participant-Years For First Occurrence of Stroke or Systemic Embolism (SE) Events After Index Date in Obese Participants | 1.51 Events Per 100 Participant-Years |
Comparison: Cox Proportional Hazards Model was used to compare the risk of stroke/SE between cohorts.p-value: 0.08895% CI: [0.66, 1.03]Cox Proportional Hazards Model
Secondary
Time in Therapeutic Range (TTR) During Follow-up Period
TTR was computed using INR values among warfarin participants during the follow-up. TTR was calculated based on the percentage of time a participant remained in therapeutic range evaluated during the entire follow-up period. TTR \>=65 percent (%) was observed as good and TTR less than (\<) 65% was observed as poor.
Time frame: From first dose of study drug to follow-up period or within 30 days from last prescription date (data collected and observed retrospectively for 3.5 years)
Population: TTR was calculated only for the warfarin arm, therefore data was not collected/observed for DOACs cohorts - apixaban, dabigatran, rivaroxaban.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Warfarin | Time in Therapeutic Range (TTR) During Follow-up Period | 14 Percentage of time |