Replication of the ROCKET-AF Anticoagulant Trial in Healthcare Claims Data
Conditions: Atrial Fibrillation
Sponsor: Brigham and Women's Hospital

Rivaroxaban versus Warfarin in Patients with 
Atrial Fibrillation (ROCKET AF Trial) 
DUPLICATE-ROCKET AF 
September 14, 2021 
NCT04593056 

Effectiveness research with Real World Data to support FDA’s regulatory decision making 
 
 
ϭ
1. RCT DeƚailƐ 
 
1.1 Title 
Riǀaƌoǆaban ǀeƌƐƵƐ Waƌfaƌin in PaƚienƚƐ ǁiƚh Aƚƌial Fibƌillaƚion ;ROCKET AF ƚƌialͿ 
 
1.2 Intended aim(s) 
To compare the risk of stroke or systemic embolism in nonvalvular atrial fibrillation (AF) patients at increased risk for stroke 
with rivaroxaban versus warfarin use.  
 
1.3 Primary endpoint for replication 
The primary outcome of the study was composite of stroke (ischemic or hemorrhage) and systemic embolism.  
 
1.3.1 Required power for primary endpoint and noninferiority margin (if applicable) 
The test was designed for noninferiority.  The most conservative approach was chosen, selecting the lower limit, ϭ.ϰϲ to 
obtain a ϵϱй power with a ϭ-sided α equal to 0.0Ϯϱ.  With expected study duration was ϰ0 months, project event rate of 
Ϯ.ϯй per ϭ00 patient years in the warfarin group, and ϭϰй annual attrition rate, ϰ0ϱ events were selected as the 
prespecified target to ensure a robust statistical result.  
 
1.4 Secondary endpoint for replication (assay sensitivity) and RCT finding 
Major bleeding; HR с ϭ.0ϰ (ϵϱй CI 0.ϵ0-ϭ.Ϯ0) 
 
1.5 Trial estimate 
HR с 0.ϳϵ (ϵϱй CI 0.ϲϲ-0.ϵϲ) comparing rivaroxaban vs warfarin (Patel et al., Ϯ0ϭϭ) 
 
2. PeƌƐon ƌeƐƉonƐible foƌ imƉlemenƚaƚion of ƌeƉlicaƚion in Aeƚion 
Dureshahwar Jawaid, MPH, Ajinkya Pawar, Ph.D., and Hemin Lee, MD, MPH implemented the study design in the Aetion Evidence 
Platform. They are not responsible for the validity of the design and analytic choices. All implementation steps are recorded and 
the implementation history is archived in the platform.   
 
3. Daƚa SoƵƌce;ƐͿ 
United/Optum, Truven/MarketScan, Medicare  

Effectiveness research with Real World Data to support FDA’s regulatory decision making!
!
!
Ϯ
#
&" SƚƵdǇ DeƐign Diagƌam#
The study design diagram visualizes key aspects of the longitudinal study design for expedited review.!
!
!"#$%%&'"()*++'++&'"(),-".$,
/*0+)123456)57
8$9*#-*('):++'++&'"();-".$,
/*0+)123456)57
;*+<$=();-".$,
>?$)@-9*#$A*B*")$#);*#C*#-"D
/*0+)123456)237
E?8F)G)H)IJ)KG)/A)$C):L)+'M*#*('.)B0)*()%'*+()3N).*0+)
/*0+)12IOP6)57
8$<$#()!"(#0)/*(')>/*0)5D
1/-+M'"+*(-$")$C)@-9*#$A*B*")Q@
;*#C*#-"7
R-&'
!"#$%&'!$(%)(*'– +,-./0'12'0+314'+/543-103,6
L$%%$,)SM);-".$,
/*0+)136)T'"+$#*7
E?8FSUEQ?)T#-('#-*),-".$,)>E?8FD
:V')K34)0#+
/*0+)123456)57
!W8FJ X-(#*%)+('"$+-+6)Y#$+(<'(-T)<'*#()9*%9'6):(#-*%)
&0A$&*6)F'C()9'"(#-T=%*#)(<#$&B=+6):T(-9')
'".$T*#.-(-+)*".):T(-9')-"('#"*%)B%''.-"V
/*0+)123456)57
/*0)5
5+371+8',90-,7/:;<=
•
!"#$%&
•
!'("&)*+,&)-$.*()
I?8F)IZ: U(#$['6)U0+('&-T)'&B$%-+&6)$#)RE:
/*0+)12:%%)/*(*6)57
!W8FJ)\-+($#0)$C)&*]$#)+=#V'#06)\'&$##<*V-T).-+$#.'#6)
E"(#*T#*"-*%)"'$M%*+&6):^)&*%C$#&*(-$"6)8'#'B#*%)*"'=#0+&6)
*".)R<#$&B$T0($M'"-*
/*0+)12I56)57
('-"&#>)$&%'?)$@")$(
•
/++0##&1+&,$2,$0"+$)&
•
3&4"5
•
!"4#",$2,466*"*$14.,789$(0#&
•
716,$2,*16&8,&89$(0#&
•
3*(&1#$..)&1"
•
!9&+*2*&6,34"&,#&4+5&6
•
!:*"+5,;:*"5*1,+$)94#*($1,<#9=
•
>0#(*1<,5$)&,46)*((*$1
E?8F)N8J)Age >75
E?8F)NZJ)\("
/*0+)123456)57
I?8F)N/: R3/X)$#)RG/X
/*0+)12:%%)/*(*6)57
E?8F)NJ)!-(<'#)
E?8FN)$#)G)$#)&$#')
$C)N:)– N/
!W8FJ X*%-V"*"()<0M'#('"+-$")$#)\0M'#('"+-9')T#-+-+
/*0+)123456)57
!W8FJ)U(#$[')M%=+).-+*B%-"V)
+(#$[')'CC'T(+
/*0+12_56)57
!W8FJ)RE:)
/*0+)12I6)57
0 1
7
!W8FJ Y!6)/^R)*".)(#'*(&'"(),-(<)*+M-#-").$+')K355&V)
1/*0+)123456)57
I?8F)N: U(#$['6)U0+('&-T)'&B$%-+&6)$#)RE:
/*0+)12:%%)/*(*6)57
!W8FJ)R#'*(&'"(),-(<)
C-B#-"$%0(-T)*V'"(+)
/*0+)12356)57
!W8FJ)R#'*(&'"(),-(<)*+M-#-")`)
(<-'"$M0#-.-"'+)$#)8*"V#'%$#
/*0+)12P6)57
I?8F)N:: \L)*".a$#)F^!L
/*0+)12:%%)/*(*6)57
!W8FJ :"'&-*6)Y#'V"*"T06)Z#'*+(C''.-"V6)b"$,")\E^)
-"C'T(-$"6)8b/)+(*V')NaPa!U@/6)/-*%0+-+6)F-9'#).-+'*+'6)
88E)Kc356):%T$<$%)$#).#=V)*B=+'6)*".)?$"2T$&M%-*"T'
/*0+)123456)57
!W8FJ)R#'*(&'"(),-(<)
8dZ)-"<-B-($#+)a)8dZ)
-".=T'#+
/*0+)12N6)57

Effectiveness research with Real World Data to support FDA’s regulatory decision making 
 
 
ϯ
 
5. Cohoƌƚ Idenƚificaƚion  
 
5.1 Cohort Summary 
This study will involve a new user, parallel group, propensity score-matched, retrospective cohort study design comparing 
rivaroxaban (at a daily dose of Ϯ0mg or ϭϱ mg) to warfarin users. The patients will be required to have continuous enrollment 
during baseline period of ϭϴ0 days before initiation of rivaroxaban or warfarin (index date). We will restrict the analyses to 
patients with a diagnosis of atrial fibrillation with risk factors for stroke or systemic embolism. 
 
5.2 Important steps for cohort formation 
 New users (defined as no use in ϭϴ0 days prior to index date) of an exposure and a comparator drug will be identified. 
 
5.2.1 Eligible cohort entry dates 
      Rivaroxaban was approved for non-valvular atrial fibrillation on November ϰ, Ϯ0ϭϭ. 
x For Marketscan: November ϰ, Ϯ0ϭϭ -December ϯϭ, Ϯ0ϭϴ (end of data availability). 
x For Medicare: November ϰ, Ϯ0ϭϭ -December ϯϭ, Ϯ0ϭϳ (end of data availability).  
x For Optum: November ϰ, Ϯ0ϭϭ -December ϯϭ, Ϯ0ϭϵ (end of data availability). 
 
5.2.2 Specify inclusion/exclusion criteria for cohort entry and define the index date 
Inclusion and exclusion criteria were adapted from the trial as closely as possible. Definitions for all inclusion/exclusion are provided 
in AƉƉendiǆ A and are summarized in the flowcharts below. 
 
5.3 Flowchart of the study cohort assembly 
For rivaroxaban vs. warfarin 
  
Optum 
Truven 
Medicare 
  
Less 
Excluded 
Patients 
Remaining 
Patients 
Less 
Excluded 
Patients 
Remaining 
Patients 
Less 
Excluded 
Patients 
Remaining 
Patients 
All patients 
  
ϳϱ,ϴϵϰ,ϲϰϮ 
  
Ϯ00,Ϯ0ϯ,ϵ0ϴ 
  
ϲ,ϴϴϲ,ϵ0ϴ 
Did not meet cohort entry criteria 
-ϳϰ,ϵϲ0,ϮϴϮ 
ϵϯϰ,ϯϲ0 
-ϭϵϵ,0ϳϯ,ϴϭϮ 
ϭ,ϭϯ0,0ϵϲ 
-Ϯ,0Ϯϴ,ϰϲϭ 
ϰ,ϴϱϴ,ϰϰϳ 
Excluded due to insufficient enrollment 
-ϵϮ,ϯ0ϭ 
ϴϰϮ,0ϱϵ 
-ϵϱ,0ϵϭ 
ϭ,0ϯϱ,00ϱ 
-ϭ,ϱϱϭ,ϭϭϰ 
ϯ,ϯ0ϳ,ϯϯϯ 

Effectiveness research with Real World Data to support FDA’s regulatory decision making 
 
 
ϰ
Excluded due to prior use of referent 
-ϰϴϮ,ϯϵϴ 
ϯϱϵ,ϲϲϭ 
-ϲϮϮ,ϱϯϴ 
ϰϭϮ,ϰϲϳ 
-Ϯ,0ϴ0,0ϲϵ 
ϭ,ϮϮϳ,Ϯϲϰ 
Excluded due to prior use of exposure 
-Ϯ0ϱ,ϱϲϱ 
ϭϱϰ,0ϵϲ 
-Ϯ0ϰ,ϰϮϱ 
Ϯ0ϴ,0ϰϮ 
-ϲϲ0,ϳϵϲ 
ϱϲϲ,ϰϲϴ 
Excluded because patient qualified in >1 exposure category 
-ϳ 
ϭϱϰ,0ϴϵ 
-Ϯϲ 
Ϯ0ϴ,0ϭϲ 
-ϴϭ 
ϱϲϲ,ϯϴϳ 
Excluded based on Age 
-ϲϮϰ 
ϭϱϯ,ϰϲϱ 
0 
Ϯ0ϴ,0ϭϲ 
-ϭϱϱ 
ϱϲϲ,ϮϯϮ 
Excluded based on Gender 
0 
ϭϱϯ,ϰϲϱ 
0 
Ϯ0ϴ,0ϭϲ 
0 
ϱϲϲ,ϮϯϮ 
Excluded based on Inclusion #1 - Age >=18 
-ϴϲ 
ϭϱϯ,ϯϳϵ 
-Ϯϲϰ 
Ϯ0ϳ,ϳϱϮ 
-ϲϱ 
ϱϲϲ,ϭϲϳ 
Excluded based on Inclusion #2 & 3 - Atrial fibrillation 
-ϴϯ,ϰϯϴ 
ϲϵ,ϵϰϭ 
-ϭϮϵ,ϭϳϮ 
ϳϴ,ϱϴ0 
-ϯϰϴ,ϱϮϭ 
Ϯϭϳ,ϲϰϲ 
Excluded based on Inclusion #4 
-ϭϯ,Ϯϵϳ 
ϱϲ,ϲϰϰ 
-ϭϲ,0ϰϲ 
ϲϮ,ϱϯϰ 
-ϯϲ,ϭϯϲ 
ϭϴϭ,ϱϭ0 
Excluded based on Exclusion #1a - Mitral stenosis 
-Ϯϳϱ 
ϱϲ,ϯϲϵ 
-ϭϱϰ 
ϲϮ,ϯϴ0 
-ϯϵϵ 
ϭϴϭ,ϭϭϭ 
Excluded based on Exclusion #1b - Prosthetic heart valve 
-ϭ,Ϯϯϴ 
ϱϱ,ϭϯϭ 
-ϳϴϵ 
ϲϭ,ϱϵϭ 
-ϯ,0ϭϲ 
ϭϳϴ,0ϵϱ 
Excluded based on Exclusion #1e - atrial myxoma or left ventricular 
thrombus 
-ϭϱϴ 
ϱϰ,ϵϳϯ 
-ϯϱ 
ϲϭ,ϱϱϲ 
-Ϯϯϰ 
ϭϳϳ,ϴϲϭ 
Excluded based on Exclusion #1f - Active infective endocarditis 
-Ϯϳϵ 
ϱϰ,ϲϵϰ 
-ϭϯϴ 
ϲϭ,ϰϭϴ 
-ϰ0ϭ 
ϭϳϳ,ϰϲ0 
Excluded based on Exclusion #2a - Active bleeding or bleeding history 
-ϯ,ϰϭϯ 
ϱϭ,Ϯϴϭ 
-Ϯ,ϳϭϲ 
ϱϴ,ϳ0Ϯ 
-ϴ,Ϯϱϲ 
ϭϲϵ,Ϯ0ϰ 
Excluded based on Exclusion #2b.1 - Major Surgery 
-ϭ,ϱϲϰ 
ϰϵ,ϳϭϳ 
-ϭ,ϱϲϭ 
ϱϳ,ϭϰϭ 
-ϲ,ϰϴϰ 
ϭϲϮ,ϳϮ0 
Excluded based on Exclusion #2b.2 - Bleeding diathesis 
-ϭ,Ϯϯϱ 
ϰϴ,ϰϴϮ 
-ϴϴϱ 
ϱϲ,Ϯϱϲ 
-ϯ,ϴϯϮ 
ϭϱϴ,ϴϴϴ 
Excluded based on Exclusion #2b.3 - Intracranial neoplasm, AV 
malformation, cerebral aneurysm 
-Ϯϱϵ 
ϰϴ,ϮϮϯ 
-Ϯϴϯ 
ϱϱ,ϵϳϯ 
-ϰϮϮ 
ϭϱϴ,ϰϲϲ 
Excluded based on Exclusion #2d - Thrombocytopenia 
0 
ϰϴ,ϮϮϯ 
0 
ϱϱ,ϵϳϯ 
0 
ϭϱϴ,ϰϲϲ 
Excluded based on Exclusion #2e - Uncontrolled hypertension 
-ϰϳ 
ϰϴ,ϭϳϲ 
-ϭ0ϱ 
ϱϱ,ϴϲϴ 
-ϯ00 
ϭϱϴ,ϭϲϲ 
Excluded based on Exclusion #3a.1 - stroke plus disabling stroke effects 
-Ϯϱϳ 
ϰϳ,ϵϭϵ 
-ϭϱϮ 
ϱϱ,ϳϭϲ 
-ϴϰϳ 
ϭϱϳ,ϯϭϵ 
Excluded based on Exclusion # 3a.2 - stroke 
-ϭ0ϯ 
ϰϳ,ϴϭϲ 
-ϴϴ 
ϱϱ,ϲϮϴ 
-ϲϰϮ 
ϭϱϲ,ϲϳϳ 
Excluded based on Exclusion #3b - TIA 
-ϭϳ 
ϰϳ,ϳϵϵ 
-Ϯϱ 
ϱϱ,ϲ0ϯ 
-ϭϮϯ 
ϭϱϲ,ϱϱϰ 
Excluded based on Exclusion #3c - DVT & PE  
-ϭ,0ϵϱ 
ϰϲ,ϳ0ϰ 
-ϴϱϯ 
ϱϰ,ϳϱ0 
-ϯ,ϭϴϱ 
ϭϱϯ,ϯϲϵ 
Excluded based on Exclusion #3d.1 - Use of aspirin > 100 mg, #3d.2 - 
Use of fibrinolytic agents, #3d.3 - Use of Aspirin + thienopyridines, 
#3d.4 - Use of cangrelor, #3f – Use of CYP inhibitors, #3g - Use of CYP 
inducers 
-ϭ,0Ϯ0 
ϰϱ,ϲϴϰ 
-ϭ,0Ϯϰ 
ϱϯ,ϳϮϲ 
-ϰ,ϱ0ϯ 
ϭϰϴ,ϴϲϲ 
Excluded based on Exclusion #3h – Anemia & #3i - Pregnancy 
-ϭ,ϯϴϮ 
ϰϰ,ϯ0Ϯ 
-ϭ,Ϯϵϰ 
ϱϮ,ϰϯϮ 
-ϲ,ϵϰ0 
ϭϰϭ,ϵϮϲ 
Excluded based on Exclusion #3k - HIV infection 
-ϭϯ 
ϰϰ,Ϯϴϵ 
-ϳ 
ϱϮ,ϰϮϱ 
-ϭϮ 
ϭϰϭ,ϵϭϰ 

Effectiveness research with Real World Data to support FDA’s regulatory decision making 
 
 
ϱ
Excluded based on Exclusion #3l - Severe renal impairment 
-ϯ,Ϯϴϭ 
ϰϭ,00ϴ 
-Ϯ,0ϭϮ 
ϱ0,ϰϭϯ 
-ϳ,ϯϵϭ 
ϭϯϰ,ϱϮϯ 
Excluded based on Exclusion #3m - Liver disease 
-ϭϵϮ 
ϰ0,ϴϭϲ 
-ϭϳ0 
ϱ0,Ϯϰϯ 
-ϰϲϲ 
ϭϯϰ,0ϱϳ 
Excluded based on Exclusion #4a - CCI (180 days)- ICD9 and ICD10 v2 
-ϰ0 
ϰ0,ϳϳϲ 
-ϯϭ 
ϱ0,ϮϭϮ 
-ϰ00 
ϭϯϯ,ϲϱϳ 
Excluded based on Exclusion #4b - drug addiction or alcohol abuse 
-ϭϱϳ 
ϰ0,ϲϭϵ 
-ϭ0ϲ 
ϱ0,ϭ0ϲ 
-Ϯϯϭ 
ϭϯϯ,ϰϮϲ 
Excluded based on Exclusion #4f - Non-compliance 
-ϭϱ 
ϰ0,ϲ0ϰ 
-Ϯϭ 
ϱ0,0ϴϱ 
-ϭϵϲ 
ϭϯϯ,Ϯϯ0 
Final cohort 
  
ϰϬ͕ϲϬϰ 
  
ϱϬ͕Ϭϴϱ 
  
ϭϯϯ͕ϮϯϬ 
Due to CMS cell suppression policy, all values less than ϭϭ are denoted with ** 
* Medicare database includes all patients using a novel oral anticoagulant and a subset of patients using warfarin during Ϯ0ϭϭ-Ϯ0ϭϳ. 
 
6. VaƌiableƐ  
 
6.1 Exposure-related variables:  
 
Study drug:  
The study exposure of interest is initiation of rivaroxaban. Initiation will be defined by no use of rivaroxaban or a comparator in the 
prior 6 months before treatment initiation (washout period). 
 
Comparator agents- 
x Initiators of rivaroxaban will be compared to initiators of- 
o Warfarin 
 
6.2 Covariates: 
x Age 
x Sex 
x Combined Comorbidity Index (CCI), measured over the baseline covariate assessment period, defined as ϭϴ0 days prior to 
and including index date 
 
Covariates listed above represent only a small subset of covariates that will ultimately be controlled for in the design and 
analysis. We use the covariates above only for initial feasibility analyses to judge whether there is likely to be sufficient 
overlap between treatment groups to proceed with the study. Remaining covariates are defined only after the study has 
passed the initial feasibility analysis and the initial power assessment and are listed in Table ϭ (AƉƉendiǆ B).  

Effectiveness research with Real World Data to support FDA’s regulatory decision making 
 
 
ϲ
 
6.3 Outcome variables and study follow-up:  
 
6.3.1 Outcome variables 
 
Primary Effectiveness outcomes of interest (definitions provided in Appendix A):  
x Primary outcome: stroke (hemorrhagic, ischemic) and systemic embolism  
x Secondary outcome: Individual components 
o Hospital admission for stroke (principal diagnosis position) 
o Hospital admission for systemic embolism (principal diagnosis position) 
 
Control outcomes of interest (control outcomes only serve to assess aspects of study validity but are not further interpreted):  
1. Major bleeding 
 
6.3.2 Study follow-up 
Both as-treated (AT) and intention-to-treat (ITT) analyses will be conducted with treatment defined as the index drug on day of 
cohort entry. Because adherence in the real-world databases is expected to be much worse than in the trial, the AT analysis is the 
primary analysis, as it targets the relative hazard of outcomes on treatment. 
 
For the as-treated analyses, the follow-up will start the day after initiation of rivaroxaban and comparator and will continue until the 
earliest date of the following events: 
x The first occurrence of the outcome of interest, unless otherwise specified for selected outcomes,  
x The date of end of continuous registration in the database, 
x End of the study period, 
x Measured death event occurs, 
x Nursing home admission 
o Nursing home admissions are considered a censoring event because the data sources utilized typically provide little to 
no data on a patient, particularly on drug utilization, after admission. We will utilize this as an exclusion reason for 
cohorts for the same reason. 

Effectiveness research with Real World Data to support FDA’s regulatory decision making 
 
 
ϳ
x The date of drug discontinuation, defined as the date of the last continuous treatment episode of the index drug 
(rivaroxaban and comparator) plus a defined grace period (i.e., 10 days after the end of the last prescription’s days’ supply in 
main analyses). 
x  The date of augmentation or switching from exposure to comparator or vice versa or augmentation/switching to any other 
NOAC (e.g. switching from rivaroxaban or warfarin to apixaban would be a censoring event); 
o A dosage change on the index treatment does not fulfill this criterion 
o An added treatment that is not part of the exposure or comparator group does not fulfill this criterion  
 
 
For the intention-to-treat (ITT) analyses, the censoring based on the augmentation/switching and treatment discontinuation 
will be replaced with a maximum allowed follow-up time of 365 days.  
 
 
7. Iniƚial FeaƐibiliƚǇ AnalǇƐiƐ  
Aetion report name: 
 
For rivaroxaban vs. warfarin  
Optum- https://bwh-dope.aetion.com/projects/details/ϭϯϭ0/results/ϱϴ0ϱϰ/result/0 
Truven- https://bwh-dope.aetion.com/projects/details/ϭϯϭϯ/results/ϱϴ0ϱϱ/result/0 
Medicare- https://bwh-dope.aetion.com/projects/details/ϭϯϰϭ/results/ϱϴ0ϱϴ/result/0  
 
Date conducted: 0ϵ/0Ϯ/Ϯ0Ϯ0 
 
Complete Aetion feasibility analysis using age, sex, and CCI as the only covariates and the primary endpoint (Section ϲ.ϯ.ϭ) as the 
outcome. No measures of association will be computed nor will incidence rates stratified by treatment group. 
 
x Report patient characteristics by treatment group 
x Report summary parameters of study population 
x Report median follow-up time by treatment group 
x Report reasons for censoring in the overall study population 
 
 

Effectiveness research with Real World Data to support FDA’s regulatory decision making 
 
 
ϴ
8. Iniƚial Poǁeƌ AƐƐeƐƐmenƚ 
 
Aetion report name: 
For rivaroxaban vs. warfarin 
Optum- https://bwh-dope.aetion.com/projects/details/ϭϯϭ0/results/ϱϴ0ϱϲ/result/0  
Truven- https://bwh-dope.aetion.com/projects/details/ϭϯϭϯ/results/ϱϴ0ϱϳ/result/0  
Medicare- https://bwh-dope.aetion.com/projects/details/ϭϯϰϭ/results/ϱϴ0ϱϵ/result/0  
 
 
Date conducted: 0ϵ/0Ϯ/Ϯ0Ϯ0 
 
In order to complete the initial power analysis, the dummy outcome of a ϵ0-day gap in database enrollment will be used. This 
outcome is used to ensure that no information on the comparative risks of the outcomes of interest are available at this stage. 
Complete a ϭ:ϭ PS-matched comparative analysis using this outcome. PS should include only ϯ covariates: age, sex, and combined 
comorbidity index. Power calculations are based on the formulas from Chow et al. (Ϯ00ϴ). 
 
x Stop analyses until feasibility and power are reviewed by primary investigators and FDA. Reviewers evaluate the results of the 
analyses described above in Sections ϳ and ϴ, including numbers of patients, patient characteristics, follow-up time, and reasons 
for censoring by treatment group, as well as overall rates of outcomes and study power. These parameters are re-evaluated and 
reported in the subsequent sections, after incorporating feedback and refining the protocol. 
 
Reviewed by PI: 
Jessica Franklin 
Date reviewed: 
ϲ/ϯ/Ϯ0 
Reviewed by FDA: 
Ken Quinto 
Date reviewed: 
ϲ/ϯ0/Ϯ0 
Reasons for stopping 
analysis (if required): 
 
 
9. Balance AƐƐeƐƐmenƚ 
 
Aetion report name: 
Optum- https://bwh-dope.aetion.com/projects/details/ϭϯϭ0/results/ϱϳϵϯϯ/result/0  
Marketscan- https://bwh-dope.aetion.com/projects/details/ϭϯϭϯ/results/ϱϳϵϯϰ/result/0  
Medicare- https://bwh-dope.aetion.com/projects/details/ϭϯϰϭ/results/ϱϳϵϴϭ/result/0  

Effectiveness research with Real World Data to support FDA’s regulatory decision making 
 
 
ϵ
 
Date conducted: ϴ/Ϯϳ/Ϯ0Ϯ0 (Medicare ϴ/ϯ0/Ϯ0Ϯ0) 
 
After review of initial feasibility and power analyses, complete creation of the remaining covariates (see Table ϭ below for list of 
covariates). Again, using the dummy outcome of a ϵ0-day gap in database enrollment, complete a ϭ:ϭ PS-matched analysis. The PS 
should include the complete list of covariates (excluding laboratory values, which are missing in some patients). 
 
x Provide plot of PS distributions stratified by treatment group. 
 
Note- Please refer to AƉƉendiǆ B.  
 
x Report covariate balance after matching. 
 
Note- For Table ϭ, please refer to AƉƉendiǆ B.  
 
x Report reasons for censoring by treatment group. 
  
Overall 
Referent 
Exposure 
Dummy Outcome 
0 (0.00%) 
0 (0.00%) 
0 (0.00%) 
Death 
1,879 (1.83%) 
946 (1.84%) 
933 (1.82%) 
Start of an additional exposure 
3,238 (3.15%) 
1,642 (3.20%) 
1,596 (3.11%) 
End of index exposure 
71,983 (70.13%) 
36,022 (70.19%) 
35,961 
(70.07%) 
Specified date reached (Dec 
17/Dec 18/Dec 19) 
6,822 (6.65%) 
3,196 (6.23%) 
3,626 (7.07%) 
End of patient enrollment 
5,237 (5.10%) 
2,408 (4.69%) 
2,829 (5.51%) 
Switch to other NOACs (for 
censoring) + nursing home 
admission 
13,477 (13.13%) 
7,104 (13.84%) 
6,373 (12.42%) 
 
 
 

Effectiveness research with Real World Data to support FDA’s regulatory decision making 
 
 
ϭ0
x Report follow-up time by treatment group. 
Median Follow-Up Time (Days) [IQR] 
Patient Group 
Optum 
Truven 
Medicare 
Overall Patient Population 
98 [38-209] 
98 [44-236] 
98 [38-206] 
Referent 
98 [38-190] 
98 [44-192] 
98 [38-188] 
Exposure 
98 [38-231] 
119 [44-281] 
98 [38-228] 
 
x Report overall risk of the primary outcome. 
  
Optum 
MarketScan 
Medicare 
Pooled 
Risk per 1,000 patients 
ϳ.00 
ϳ.ϯϯ 
ϭϮ.0ϱ 
ϭ0.0ϴ 
 
 
10. Final Poǁeƌ AƐƐeƐƐmenƚ 
 
Date conducted:  
 
x Re-calculate power in the appropriate excel table, using the revised number of matched patients from the PS-match in Section ϵ. 
All other parameters in the table should be the same as in Section ϴ. 
 
For rivaroxaban vs. warfarin 
 
 
 
 
 
 
 
 
 
 
 
 

Effectiveness research with Real World Data to support FDA’s regulatory decision making 
 
 
ϭϭ
o Pooled 
 
Superiority Analysis
Number of patients matched
102,636
Reference
51,318
Exposed
51,318
Risk per 1,000 patients
10.08
Desired HR from RCT
0.79
Alpha (2-sided)
0.05
Number of events expected
1034.57088
Power
0.966450516
Non-inferiority Analysis
Number of patients matched
102,636
Reference
51,318
Exposed
51,318
Risk per 1,000 patients
10.08
Assumed HR from RCT
1
Alpha (2-sided)
0.05
Non-inferiority margin
1.46
Number of events expected
1034.57088
Power
0.999981559 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Effectiveness research with Real World Data to support FDA’s regulatory decision making 
 
 
ϭϮ
 
 
o Optum 
Superiority Analysis
Number of patients matched
17,900
Reference
8,950
Exposed
8,950
Risk per 1,000 patients
7.00
Desired HR from RCT
0.79
Alpha (2-sided)
0.05
Number of events expected
125.3
Power
0.261393559
Non-inferiority Analysis
Number of patients matched
17,900
Reference
8,950
Exposed
8,950
Risk per 1,000 patients
7.00
Assumed HR from RCT
1
Alpha (2-sided)
0.05
Non-inferiority margin
1.46
Number of events expected
125.3
Power
0.562809862 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Effectiveness research with Real World Data to support FDA’s regulatory decision making 
 
 
ϭϯ
 
o MarketScan 
Superiority Analysis
Number of patients matched
22,600
Reference
11,300
Exposed
11,300
Risk per 1,000 patients
7.33
Desired HR from RCT
0.79
Alpha (2-sided)
0.05
Number of events expected
165.658
Power
0.329138572
Non-inferiority Analysis
Number of patients matched
22,600
Reference
11,300
Exposed
11,300
Risk per 1,000 patients
7.33
Assumed HR from RCT
1
Alpha (2-sided)
0.05
Non-inferiority margin
1.46
Number of events expected
165.658
Power
0.682759594 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Effectiveness research with Real World Data to support FDA’s regulatory decision making 
 
 
ϭϰ
 
o Medicare 
 
Superiority Analysis
Number of patients matched
62,136
Reference
31,068
Exposed
31,068
Risk per 1,000 patients
12.05
Desired HR from RCT
0.79
Alpha (2-sided)
0.05
Number of events expected
748.7388
Power
0.897079133
Non-inferiority Analysis
Number of patients matched
62,136
Reference
31,068
Exposed
31,068
Risk per 1,000 patients
12.05
Assumed HR from RCT
1
Alpha (2-sided)
0.05
Non-inferiority margin
1.46
Number of events expected
748.7388
Power
0.999353731 
 
x Stop analyses until balance and final power assessment are reviewed by primary investigators, FDA, and assigned members of 
advisory board. 
Reviewed by PI: 
Jessica Franklin 
Date reviewed: 
ϵ/ϴ/Ϯ0 
Reviewed by FDA: 
Ken Quinto 
Date reviewed: 
ϵ/Ϯϵ/Ϯ0 
Reasons for stopping 
analysis (if required): 
 
 
11. SƚƵdǇ Confidence and ConceƌnƐ 
 
Deadline for voting on study confidence and listing concerns: 
Date votes and concerns are summarized:    
 
x If final feasibility and power analyses are reviewed and approved, proceed to the remaining protocol steps. 

Effectiveness research with Real World Data to support FDA’s regulatory decision making 
 
 
ϭϱ
x All study team and advisory board members that review this protocol should at this stage provide their level of confidence for the 
success of the RWD study in the Google Form. This form also provides space for reviewers to list any concerns that they feel may 
contribute to a failure to replicate the findings of the RCT, including differences in study populations, poor measurement of study 
variables, or residual confounding. All responses will be kept confidential and individual-level results will only be shared with the 
individual respondent. 
x After the deadline for voting has passed, provide the distribution of responses and summarize all concerns here. 
 
12. RegiƐƚeƌ ƐƚƵdǇ Ɖƌoƚocol on clinicalTƌialƐ͘goǀ 
 
Date conducted:    
 
x Register the study on clinicalTrials.gov and upload this document. 
 
13. ComƉaƌaƚiǀe AnalǇƐeƐ 
 
Aetion report name: 
Date conducted:    
 
13.1 
For primary analysis:  
 
13.2 
For sensitivity analyses: 
 
 
14.  ReƋƵeƐƚed ReƐƵlƚƐ  
 
14.1 
Table ϭ: Baseline characteristics before and after adjustment 
 
Vaƌiable 
 
Befoƌe adjƵƐƚmenƚ 
Afƚeƌ adjƵƐƚmenƚ 
Refeƌenƚ 
EǆƉoƐƵƌe 
Sƚd͘ diff͘ 
Refeƌenƚ 
EǆƉoƐƵƌe 
Sƚd͘ diff͘ 
Number of patients 
 
 
- 
 
 
- 
Age categories 
 
 
 
 
 
 
… 
 
 
 
 
 
 

Effectiveness research with Real World Data to support FDA’s regulatory decision making 
 
 
ϭϲ
 
 
14.2 
Table Ϯ: Follow-up time 
 
Patient Group 
Median Follow-Up Time (Days) [IQR] 
Overall Patient Population 
 
Referent 
 
Exposure 
 
 
14.3 
Table ϯ: Censoring events 
 
 
Overall 
Referent 
Exposure 
Outcome 
 
 
 
Death 
 
 
 
Start of an additional exposure 
 
 
 
End of index exposure 
 
 
 
Specified date reached 
 
 
 
End of patient data 
 
 
 
End of patient enrollment 
 
 
 
… 
 
 
 
 
14.4 
Table ϰ: Results from primary analyses; 
 
AnalǇƐiƐ 
No͘ eǆƉoƐed eǀenƚƐ 
No͘ ƌefeƌenƚ eǀenƚƐ 
EǆƉoƐed ƌaƚe 
Refeƌenƚ ƌaƚe 
HR ;ϵϱй CIͿ 
Crude 
 
 
 
 
 
Analysis ϭ 
 
 
 
 
 
Analysis Ϯ 
 
 
 
 
 
... 
 
 
 
 
 
HR, Hazard Ratio; CI, Confidence Interval. 
14.5 
Table ϱ: Results from secondary analyses; 

Effectiveness research with Real World Data to support FDA’s regulatory decision making 
 
 
ϭϳ
15.  RefeƌenceƐ 
 
 
Chow S, Shao J, Wang H. Ϯ00ϴ.  Sample Siǌe CalcƵlaƚions in Clinical Research. Ϯnd Ed. Chapman & Hall/CRC Biostatistics Series. Ɖage 
ϭϳϳ 
 
Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, Breithardt G, Halperin JL, Hankey GJ, Piccini JP, Becker RC. Rivaroxaban 
versus warfarin in nonvalvular atrial fibrillation. New England Journal of Medicine. 2011; 365(10):883-91. 
 
 
 
 

# ROCKET-AF trial definitions 
Implementation in routine care
References/Rationale
Color coding
Please see the following Google Drive for further details or any missing information: 
https://drive.google.com/open?id=1WD618wrywYjEaXzfLTcuK-VCcnb6b-gV
Criteria
ICD-10 codes are not listed in this document because of excel cell size limitations and 
excessive number of ICD-10 codes. Full ICD-10 code lists will be available in the above 
Google Drive Folder (link above). ICD-9 to ICD-10 code conversions were completed using 
a SAS macro that implements forward/ backward mapping based on the CMS ICD-9 to ICD-
10 mapping: https://www.nber.org/data/icd9-icd-10-cm-and-pcs-crosswalk-general-
equivalence-mapping.html
Adequate mapping in claims
Rivaroxaban vs. Warfarin
Rivaroxaban 20mg OR 15mg daily (if low GFR)  vs. adjusted-dose warfarin
Intermediate mapping in claims
Poor mapping or cannot be measured in claims 
Primary endpoint of stroke (ischemic or hemorrhagic) and systemic embolism. 
Measured 1 day after drug initiation in primary diagnosis position specified below and 
inpatient care setting:
Stroke:
ICD-9 discharge diagnosis codes:
430.xx  Subarachnoid hemorrhage (SAH)
431.xx  Intracerebral hemorrhage (ICH)
433.x1  Occlusion and stenosis of precerebral arteries with cerebral infarction
434.xx (excluding 434.x0)  Occlusion and stenosis of cerebral arteries with cerebral 
infarction
436.x  Acute, but ill-defined cerebrovascular events
Systemic embolism:
ICD-9 discharge diagnosis code: 444.xx Arterial embolism
ICD-10 discharge diagnosis code: I74.x Arterial embolism and thrombosis 
For stroke:
PPV of 85% or higher for ischemic stroke
PPV ranging from 80% to 98% for hemorrhagic stroke
➜[Andrade SE, Harrold LR, Tjia J, et al. A systematic review of validated methods 
for identifying cerebrovascular accident or transient ischemic attack using 
administrative data. Pharmacoepidemiology and Drug Safety 2012;21 Suppl 1:100-
28.]
➜[Tirschwell DL, Longstreth WT, Jr. Validating administrative data in stroke 
research. Stroke; a journal of cerebral circulation 2002;33:2465-70.]
➜[Roumie CL, Mitchel E, Gideon PS, Varas-Lorenzo C, Castellsague J, Griffin MR. 
Validation of ICD-9 codes with a high positive predictive value for incident strokes 
resulting in hospitalization using Medicaid health data. Pharmacoepidemiology and 
drug safety 2008;17:20-6.]
Can't be measured in claims but not important for the 
analysis
1 Men or women aged ≥18 years
Measured on the day of drug initiation:
Age >=18 
2
Non-valvular Atrial fibrillation
Atrial fibrillation must be documented by ECG evidence (e.g., 12-lead ECG, rhythm strip, Holter, pacemaker interrogation) within 
30 days before randomization. 
In addition, subjects must have medical evidence of atrial fibrillation within 1 year before and at least one day before the 
qualifying ECG evidence. This could be obtained from a notation in the subject's record (e.g., medical chart, hospital discharge 
summary).
Measured 12 months prior to and including day of drug initiation, with >2 diagnoses 
separated by at least 14 days, in any diagnosis position and inpatient or outpatient care 
setting:
Atrial fibrillation:
ICD-9 diagnosis: 427.31
ICD-10 diagnosis: I48.0x, I48.1x, I48.2x, I48.9x 
3
Non-valvular Atrial fibrillation
Subjects with newly diagnosed atrial fibrillation are eligible provided that:
 – there is evidence that the atrial fibrillation is non-valvular
 – cardioversion is not planned 
 – there is ECG evidence on 2 occasions 24 hours apart demonstrating atrial fibrillation
For Inclusion Criteria 4
It is either 
A) History of ischemic stroke or TIA or arterial embolism 
-OR-
B) 2 of the following 4
        1) Heart failure 
          2) Hypertension 
       3) Age >=75 
         4) Diabetes
4 History of prior ischemic stroke, TIA or non-CNS systemic embolism believed to be cardioembolic in
origin 
Measured any time prior to and including day of drug initiation in any diagnosis position 
and inpatient or outpatient care setting:
Ischemic stroke:  
ICD-9 diagnosis: 433.x, 434. x, 436.xx
TIA:
ICD-9 diagnosis: 435.xx  
Systemic embolism: 
ICD-9 diagnosis: 444.xx
Patorno, Elisabetta et al. "Cardiovascular outcomes associated with canagliflozin 
versus other non-gliflozin antidiabetic drugs: population based cohort study." BMJ 
2018;360:k119 http://dx.doi.org/10.1136/bmj.k119
Patorno, Elisabetta et al. "Empagliflozin and the Risk of Heart Failure Hospitalization 
in Routine Clinical Care: A First Analysis from the Empagliflozin Comparative 
Effectiveness and Safety (EMPRISE) Study."  Circulation. 2019 Apr 8. doi: 
10.1161/CIRCULATIONAHA.118.039177
OR 2 or more of the following risk factors
4a – Heart failure and/or left ventricular ejection fraction ≤35%
Measured anytime prior to and including day of drug initiation in any diagnosis position 
and inpatient or outpatient care setting:
Heart failure:
ICD-9 diagnosis:
428.x, 398.91, 402.01, 402.11, 402.91, 404.01, 404.11, 404.91, 404.03, 404.13, 404.93
Patorno, Elisabetta et al. "Cardiovascular outcomes associated with canagliflozin 
versus other non-gliflozin antidiabetic drugs: population based cohort study." BMJ 
2018;360:k119 http://dx.doi.org/10.1136/bmj.k119
Patorno, Elisabetta et al. "Empagliflozin and the Risk of Heart Failure Hospitalization 
in Routine Clinical Care: A First Analysis from the Empagliflozin Comparative 
Effectiveness and Safety (EMPRISE) Study."  Circulation. 2019 Apr 8. doi: 
10.1161/CIRCULATIONAHA.118.039177
PRIMARY OUTCOME
Trial details- Primary indication, 4a- Unintended S with label change  HR = 0.79 (95% CI 0.66–0.96)
EXPOSURE vs. COMPARISON
INCLUSION CRITERIA
Appendix A

4b
– Hypertension (defined as use of antihypertensive medications within 6 months before the
screening visit or persistent systolic blood pressure above 140 mmHg or diastolic blood pressure
above 90 mmHg)
Measured 180 days prior to and inlcuding day of drug initiation in any diagnosis position 
and inpatient or outpatient care setting:
Hypertension:
ICD-9 diagnosis: 401.x – 405.x 
Plus following medication use within 6 months: 
Refer to the 'Hypertension meds' sheet for list of medications
Patorno, Elisabetta et al. "Cardiovascular outcomes associated with canagliflozin 
versus other non-gliflozin antidiabetic drugs: population based cohort study." BMJ 
2018;360:k119 http://dx.doi.org/10.1136/bmj.k119
Patorno, Elisabetta et al. "Empagliflozin and the Risk of Heart Failure Hospitalization 
in Routine Clinical Care: A First Analysis from the Empagliflozin Comparative 
Effectiveness and Safety (EMPRISE) Study."  Circulation. 2019 Apr 8. doi: 
10.1161/CIRCULATIONAHA.118.039177
4c – Age ≥75 years
Measured at the time of drug initiation:
Age ≥75 years
4d – Diabetes mellitus (defined as a history of type 1 or type 2 diabetes mellitus or use of antidiabetic
medications within 6 months before screening visit) 
Measured any time prior to and including day of drug initiation in diagnosis position and 
inpatient or outpatient care setting:
DM type 2:
ICD-9 diagnosis: 250.x0 or 250.x2
ICD-10 diagnosis: E11.x
DM type 1:
ICD-9 diagnosis: 250.x1 or 250.x3
ICD-10 diagnosis: E10.x
-OR-
Following drug dispensing within 6 months of drug intiation: 
Refer to the 'Diabetes meds' sheet for list of DM Drugs
Patorno, Elisabetta et al. "Cardiovascular outcomes associated with canagliflozin 
versus other non-gliflozin antidiabetic drugs: population based cohort study." BMJ 
2018;360:k119 http://dx.doi.org/10.1136/bmj.k119
Patorno, Elisabetta et al. "Empagliflozin and the Risk of Heart Failure Hospitalization 
in Routine Clinical Care: A First Analysis from the Empagliflozin Comparative 
Effectiveness and Safety (EMPRISE) Study."  Circulation. 2019 Apr 8. doi: 
10.1161/CIRCULATIONAHA.118.039177
5
Female subjects must be postmenopausal (for at least 2 years), surgically sterile, abstinent, or, if sexually active, be practicing 
an effective method of birth control (e.g., prescription oral contraceptives, contraceptive injections, intrauterine device, double-
barrier method, contraceptive patch, male partner sterilization) before entry and throughout the study; and, for those of 
childbearing potential, have a negative serum β-hCG pregnancy test at screening.
N/A
We will incorporate this by excluding 'pregnant' women below. 
6 Subjects must have signed an informed consent document indicating that they understand the purpose of and procedures 
required for the study and are willing to participate in the study
N/A
7
In order to participate in the optional pharmacogenomic component, subjects must have signed the informed consent for DNA 
research document indicating willingness to participate in the pharmacogenomics component of the study (where local 
regulations permit)
N/A
1 Cardiac-Related Conditions
1a Hemodynamically significant mitral valve stenosis
Measured 180 days prior to and including day of drug initiation in any diagnosis position 
and inpatient or outpatient care setting:
Mitral stenosis:
ICD-9 diagnosis: 396.0x, 396.1x
ICD-10 diagnosis: I34.2x, I05.1x, I05.2x
1b  Prosthetic heart valve (annuloplasty with or without prosthetic ring, commissurotomy and/or valvuloplasty are permitted)
Measured 180 days prior to and including day of drug initiation in any diagnosis position 
and inpatient or outpatient care setting:
ICD-9 diagnosis: V43.3x
ICD-10 diagnosis: Z95.2x
CPT procedure: (TAVR with prosthetic valve) 
33361, 33362, 33363, 33364, 33365, 33366, 33367, 33368, 33369, 33477,
0483T, 0484T, 0569T, 0570T
1c  Planned cardioversion (electrical or pharmacological) 
N/A
Will not capture 'planned' procedures
1d Transient atrial fibrillation caused by a reversible disorder (e.g., thyrotoxicosis, PE, recent surgery, MI)
N/A
Transient AF would not be well captured in claims. 
Joshi, Kirti K et al. “Postoperative atrial fibrillation in patients undergoing non-
cardiac non-thoracic surgery: A practical approach for the hospitalist.” Hospital 
practice (1995) vol. 43,4 (2015): 235-44. doi:10.1080/21548331.2015.1096181
1e  Known presence of atrial myxoma or left ventricular thrombus 
Measured 180 days prior to and including day of drug initiation in any diagnosis position 
and inpatient or outpatient care setting:
Atrial myxoma:
ICD-9 diagnosis: 212.7 (Benign neoplasm of heart)
ICD-10 diagnosis: D15.1 (Benign neoplasm of heart)
Left ventricular thrombus:
ICD-10 diagnosis: I51.3 (Intracardiac thrombosis) 
EXCLUSION CRITERIA
Appendix A

1f Active endocarditis
Measured 180 days prior to and including day of drug initiation in any diagnosis position 
and inpatient or outpatient care setting:
Endocarditis:
ICD-9 diagnosis: 421.xx , 424.9x
ICD-10 diagnosis: I33.xx, I38.xx, I39.xx  
Tan, Charlie et al. “Accuracy of administrative data for identification of patients with 
infective endocarditis.” International journal of cardiology vol. 224 (2016): 162-164. 
doi:10.1016/j.ijcard.2016.09.030
2 Hemorrhage Risk-Related Criteria
2a  Active internal bleeding 
Measured 180 days prior to and including day of drug initiation in any diagnosis position 
and inpatient or outpatient care setting: 
Refer to the 'Bleeding' sheet for detailed codes(includes GI bleeding, intracranial, intra-
articular bleeding mentioned in exclusion 2b)
2b
 History of or condition associated with increased bleeding risk including, but not limited to:
– Major surgical procedure or trauma within 30 days before the randomization visit
– Clinically significant gastrointestinal bleeding within 6 months before the randomization visit
– History of intracranial, intraocular, spinal, or atraumatic intra-articular bleeding
– Chronic hemorrhagic disorder
– Known intracranial neoplasm, arteriovenous malformation, or aneurysm 
 Measured 30 days prior to and including day of drug initiation in diagnosis position and 
inpatient or outpatient care setting:
1) Major surgery:
Major surgery selected from procedure codes range 40.x- 84.x 
-OR- 
2) Hemorrhagic disorder (Bleeding diathesis)
286.x Coagulation defects
287.x Purpura and other hemorrhagic conditions
-OR-
3) Intracranial neoplasm, AV malformation, aneurysm
Intracranial neoplasm
ICD-9 diagnosis: 225.xx 
ICD-10 diagnosis: D33.xx
AV malformation 
ICD-9 diagnosis:  747.81 
ICD-10 diagnosis: Q28.2x
Cerebral aneurysm:
ICD-9 diagnosis: 437.3x
ICD-10 diagnosis: I67.1
 
2c Planned invasive procedure with potential for uncontrolled bleeding, including major surgery
N/A
2d Platelet count < <90,000/μL at the screening visit 
Measured 30 days prior to and including day of drug initiation in any diagnosis position 
and inpatient or outpatient care setting:
Thrombocytopenia:
ICD-9 diagnosis: 287.3x, 287.4x, 287.5x
2e Sustained uncontrolled hypertension: systolic blood pressure ≥180 mmHg or diastolic blood pressure ≥100
mmHg 
Measured 180 days prior to and including day of drug initiation in any diagnosis position 
and Inpatient care or ED setting:
Malignant hypertension: 
ICD-9 diagnosis: 401.0x 
Hypertensive urgency/Hypertensive crisis: 
ICD-10 diagnosis: I16.xx 
3 Concomitant Conditions and Therapies
3a Severe, disabling stroke (modified Rankin score of 4 to 5, inclusive) within 3 months or any stroke within
14 days before the randomization visit 
1) Measured 90 days prior to and including day of drug initiation in position and care 
setting specified below:
Stroke(primary diagnosis position, inpatient care setting):
ICD-9 diagnosis: 430.xx, 431.xx, 433.xx, 434.xx, 436.xx,
-PLUS-
Disabling stroke effects (any position, any care setting, with 7-83 days between the 
strokes) 
ICD-9 diagnosis: 438.xx Late effects of cerebrovascular disease
ICD-10 diagnosis: 
I69.xx Sequelae of cerebrovascular disease (hemiplegia etc); 
Z73.6x Limitation of activities due to disability
2) Measured 14 days prior to and including day of drug initiation in primary diagnosis 
position and inpatient care setting: 
Stroke:
ICD-9 diagnosis: 430.xx, 431.xx, 433.xx, 434.xx, 436.xx
Patorno, Elisabetta et al. "Cardiovascular outcomes associated with canagliflozin 
versus other non-gliflozin antidiabetic drugs: population based cohort study." BMJ 
2018;360:k119 http://dx.doi.org/10.1136/bmj.k119
Patorno, Elisabetta et al. "Empagliflozin and the Risk of Heart Failure Hospitalization 
in Routine Clinical Care: A First Analysis from the Empagliflozin Comparative 
Effectiveness and Safety (EMPRISE) Study."  Circulation. 2019 Apr 8. doi: 
10.1161/CIRCULATIONAHA.118.039177
3b Transient ischemic attack within 3 days before the randomization visit
Measured 3 days prior to and including day of drug initiation in primary diagnosis position 
and inpatient care or ED setting:
TIA:
ICD-9 diagnosis: 435.xx
Appendix A

3c Indication for anticoagulant therapy for a condition other than atrial fibrillation (e.g., VTE) 
Measured 180 days prior to and including day of drug initiation in any diagnosis position 
and inpatient or outpatient care setting:
1) Pulmonary embolism (PE):
ICD-9 diagnosis: 415.xx
ICD-10 diagnosis: I26.xx, 
2) Deep vein thrombosis (DVT):
ICD-9 diagnosis: 451.xx, 453.xx
ICD-10 diagnosis: I26.xx, I80.xx, I81.xx, I82.xx, I26.xx
3d
Treatment with:
– Aspirin >100 mg daily
– Aspirin in combination with thienopyridines within 5 days before randomization
– Intravenous antiplatelets within 5 days before randomization
– Fibrinolytics within 10 days before randomization
– Note: Aspirin ≤100 mg monotherapy is allowed and thienopyridine monotherapy is allowed. 
Measured 180 days prior to and including day of drug initiation:
Aspirin dose >100mg: (Only prescription use is captured.)
Measured 10 days prior to and including day of drug initiation:
Fibrinolytic agents:
Alteplase, reteplase, tenecteplase, streptokinase, urokinase
Measured 5 days prior to and including day of drug initiation:
Aspirin (any dose) + thienopyridines (clopidogrel or prasugrel or ticlopidine)
Measured 5 days prior to and including day of drug initiation:
Cangrelor
3e Anticipated need for chronic treatment with a non-steroidal anti-inflammatory drug 
3f Systemic treatment with a strong inhibitor of cytochrome P450 3A4, such as ketoconazole or protease
inhibitors, within 4 days before randomization, or planned treatment during the time period of the study 
3g
Treatment with a strong inducer of cytochrome P450 3A4, such as rifampin/rifampicin, within 4 days
before randomization, or planned treatment during the time period of the study 
3h Anemia (hemoglobin <10 g/dL) at the screening visit
Measured 180 days prior to and including day of drug initiation in any diagnosis position 
and inpatient or outpatient care setting:
Anemia (non-deficiency/neoplastic/chemotherapy/hemorrhagic assoicated):
ICD-9 diagnosis: 282.x, 283.x, 284.x, 285.0, 285.2 (acute posthemorrhagic anemia), 285.22 
(anemia of neoplastic disease), 285.3 (antineoplastic chemotherapy induced anemia)
ICD-10 diagnosis: D55 - D62, D63.0 
3i Pregnancy or breast-feeding
Measured 180 days prior to and including day of drug initiation in any diagnosis position 
and inpatient or outpatient care setting:
Refer to the 'Pregnancy' sheet.
3j Any other contraindication to warfarin 
N/A
3k Known HIV infection at time of screening 
Following diagnosis or drugs measured 180 days prior to and including day of drug 
initiation in any diagnosis position and inpatient or outpatient care setting:
HIV Infection:
042 Human immunodeficiency virus [HIV] disease
079.53 Human immunodeficiency virus, type 2 [HIV-2]
V08 Asymptomatic human immunodeficiency virus [HIV] infection status
-OR- 
Filled prescription for HIV treatment 180 days prior to drug initiation:
Refer to the 'HIV treatment' sheet for list of treatments
Patorno, Elisabetta et al. "Cardiovascular outcomes associated with canagliflozin 
versus other non-gliflozin antidiabetic drugs: population based cohort study." BMJ 
2018;360:k119 http://dx.doi.org/10.1136/bmj.k119
Patorno, Elisabetta et al. "Empagliflozin and the Risk of Heart Failure Hospitalization 
in Routine Clinical Care: A First Analysis from the Empagliflozin Comparative 
Effectiveness and Safety (EMPRISE) Study."  Circulation. 2019 Apr 8. doi: 
10.1161/CIRCULATIONAHA.118.039177
Measured 4 days prior to and including day of drug initiation as a dispensing of the 
following: 
CYP inhibitors (selected):
ketoconazole, metronidazole, amiodarone, cimetidine, omeprazole, fluoxetine, indinavir, 
ritonavir
CYP inducers (selected):
carbamazepine, phenytoin, rifampin/rifampicin, phenobarbital
Appendix A

3l Calculated CLCR <30 mL/min at the screening visit (refer to Attachment 4 for calculating CLCR)
Measured 180 days prior to and including day of drug initiation in any diagnosis position 
and inpatient or outpatient care setting:
CKD stage 4/5/ESRD:
ICD-9 diagnosis: 585.4x, 585.5x, 585.6x
ICD-10 diagnosis: N18.4x, N18.5x, N18.6x 
-OR- 
Dialysis/ Renal transplant:
Refer to the 'Dialysis' sheet for list of codes
3m Known significant liver disease (e.g., acute clinical hepatitis, chronic active hepatitis, cirrhosis), or ALT >3x the ULN 
Measured 180 days prior to and including day of drug initiation in any 
diagnosis/procedure position and inpatient or outpatient care setting:
Liver disease: 
ICD-9 diagnosis:
070.xx, 570.xx- 573.xx 
456.0x-456.2x, 576.8x, 782.4x, 789.5x 
ICD-9 procedure:
39.1x, 42.91 
4 Study Participation and Follow-up-Related Criteria
4a Serious concomitant illness associated with a life expectancy of less than 2 years 
Measured 180 days prior to and including day of drug initiation:
CCI>=10
4b Drug addiction or alcohol abuse within 3 years before the randomization visit 
Measured 180 days prior to and including day of drug initiation in any diagnosis position 
and inpatient or outpatient care setting:
Alcohol abuse or dependence:
291.xx, 303.xx, 305.0x, 571.0x, 571.1x, 571.2x, 571.3x, 357.5x, 425.5x, E860.0x, V11.3x
Drug abuse or dependence:
292.xx, 304.xx, 305.2x-305.9x, 648.3x
Patorno, Elisabetta et al. "Cardiovascular outcomes associated with canagliflozin 
versus other non-gliflozin antidiabetic drugs: population based cohort study." BMJ 
2018;360:k119 http://dx.doi.org/10.1136/bmj.k119
Patorno, Elisabetta et al. "Empagliflozin and the Risk of Heart Failure Hospitalization 
in Routine Clinical Care: A First Analysis from the Empagliflozin Comparative 
Effectiveness and Safety (EMPRISE) Study."  Circulation. 2019 Apr 8. doi: 
10.1161/CIRCULATIONAHA.118.039177
4c Have received an experimental drug or used an experimental medical device within 30 days before the
planned start of treatment 
N/A 
4d Previous randomization in the present study or other study of rivaroxaban
N/A
4e
Known allergy or hypersensitivity to any component of rivaroxaban, warfarin or placebo excipients
(includes lactose, microcrystalline cellulose, magnesium stearate, hypromellose, macrogol, croscarmellose
sodium, sodium lauryl sulfate, titanium oxide/ferric oxide red, titanium dioxide/ferric oxide red, anhydrous
lactose, pregelatinized starch, FD&C Red #6 barium lake, FD&C Yellow #10 aluminum lake, FD&C Blue
#1 aluminum lake, FD&C Yellow #6 aluminum lake, cornstarch, lactose monohydrate) 
N/A
4f Inability or unwillingness to comply with study-related procedures 
Measured 180 days hospitalization prior to and including day of drug initiation in any 
diagnosis position and inpatient or outpatient care setting:
Non-compliance: 
ICD-9 diagnosis:
V15.81 PERSONAL HISTORY OF NONCOMPLIANCE WITH MEDICAL TREATMENT 
PRESENTING HAZARDS TO HEALTH;
V45.12 NONCOMPLIANCE WITH RENAL DIALYSIS
4g
Employees of the investigator or study center, with direct involvement in the proposed study or other
studies under the direction of that investigator or study center, as well as family members of the employees
or the investigator. 
N/A
Appendix A

Trial ID 
pNDA27
Trial Name (with web links)
ROCKET AF
Trial Name (with pdf links)
ROCKET AF
NCT
NCT00403767 
Trial category
Primary indication
Therapeutic Area
Cardiology/Vascular Diseases
Study batch
NOACs
RCT Category  
4a- Unintended S with label change
Brand Name
Xarelto 
Generic Name
rivaroxaban
Sponsor
 Janssen Pharmaceuticals
Year
2011
Measurable endpoint
Primary endpoint of stroke and systemic embolism
Exposure
Rivaroxaban
Comparator
Warfarin
Population
patients with nonvalvular atrial fibrillation who were at increased risk 
for stroke
Trial finding
HR = 0.79 (95% CI 0.66–0.96)
 No. of Patients 
                                                                                                        14,264 
Non-inferiority margin
HR = 1.46
Power
0.95 power of 95% to calculate a noninferiority margin of 1.46 with a 
one-sided alpha level of 0.025.
Blinding
Double-blinded
Statistical Method
Alternative hypothesis of non-inferiority (NI) by a NI margin of 1.46 in 
hazard ratio (HR) based on on-treatment data from the per protocol 
population. The required number of primary efficacy endpoint events 
was determined based on the following assumptions: NI margin of 
1.46, 1-sided alpha of 0.025, power of >95% when true HR is 1, and 
exponential distributions. The margin was selected based on clinical 
appropriateness and quantitative analysis of relevant studies in Hart et 
al.
Approval indication
 For the reduction in the risk of stroke and systemic embolism 
resulting from atrial fibrillation
Appendix A

Dialysis codes
ESRD, defined as 2 codes (either inpatient or outpatient), separated by at least 30 days 
Codes include:
- ICD9 prox codes: 
39.95, Hemodialysis
54.98, Peritoneal dialysis
- ICD9 dx codes: 
585.5x, Chronic kidney disease, Stage V (for ESRD with no mention of dialysis) 
585.6x, End stage renal disease (for ESRD with dialysis) 
V56.0x, encounter for dialysis NOS
V56.8x, encounter for peritoneal dialysis
V45.1x, renal dialysis status
- CPT4 codes: 
90957, 90960, ESRD related services monthly, for patients 12-19 and 20 years of age and older; with 4 or more face-to-face physician visits per 
month
90958, 90961, ESRD related services monthly, for patients 12-19 and 20 years of age and older; with 2-3 face-to-face physician visits per month
90959, 90962, ESRD related services monthly, for patients 12-19 and 20 years of age and older; with 1 face-to-face physician visit per month
90920, 90921, ESRD related services per full month; for patients 12-19 and twenty years of age and over
90924, 90925, ESRD related services (less than full month), per day; for patients 12-19 and twenty years of age and over
90935, Hemodialysis procedure with single physician evaluation
90937, Hemodialysis procedure requiring repeated evaluation(s) with or without substantial revision of dialysis prescription
90945, Dialysis procedure other than hemodialysis (eg, peritoneal dialysis, hemofiltration, or other continuous renal replacement therapies), 
with single physician evaluation
90947, Dialysis procedure other than hemodialysis (eg, peritoneal dialysis, hemofiltration, or other continuous renal replacement therapies) 
requiring repeated physician evaluations, with or without substantial revision of dialysis prescription
90965, 90966, ESRD related services for home dialysis per full month, for patients 12-19 and 20 years of age and older
90969, 90970, ESRD related services for dialysis less than a full month of service, per day; for patients 12-19 and 20 years of age and older
90989, Dialysis training, patient, including helper where applicable, any mode, completed course
90993, Dialysis training, patient, including helper where applicable, any mode, course not completed, per training session
90999, Unlisted dialysis procedure, inpatient or outpatient
99512, Home visit for hemodialysis
- HCPCS codes:
G0257, Unscheduled or emergency dialysis treatment for ESRD patient in a hospital outpatient dept. that is not certified as an ESRD facility 
G0314, G0317, ESRD related services during the course of treatment, for patients 12-19 and 20 yrs of age an over to include monitoring for the 
adequacy of nutrition, etc. w/4 or more physician visit per month
G0315, G0318, ESRD related services during the course of treatment, for patients 12-19 and 20yrs of age and over to include monitoring for the 
adequacy of nutrition etc w/2 or 3 physician visit per month
Appendix A

adequacy of nutrition, etc. w/2 or 3 physician visit per month
G0316, G0319, ESRD related services during the course of treatment, for patients 12-19 and 20 yrs of age and over to include monitoring for the 
adequacy of nutrition, etc. w/1 physician visit per month
G0322, G0323, ESRD related services for home dialysis patients per full month: for patients 12-19 and 20 yrs of age and over to include 
monitoring for adequacy of nutrition and etc.
G0326, G0327, ESRD related services for home dialysis (less than full month), per day; for patients 12-19 and 20 yrs of age and over
S9335, Home therapy, hemodialysis; administrative services, professional pharmacy services, care coordination, and all necessary supplies and 
equipment (drugs and nursing services coded separately), per diem
S9339, Home therapy, peritoneal dialysis, administrative services, care coordination and all necessary supplies and equipment, per diem
OR
Kidney transplant, defined as either 1 inpatient or 1 outpatient code
Codes include:
-ICD9 dx codes:
V42.0x, Kidney transplant status
996.81 Complications of transplanted kidney
-ICD9 prox codes: 
55.6x, Transplant of kidney (Exclude 55.61)
- CPT4 codes:
50360, Renal allotransplantation, implantation, graft, w/o donor & recipient nephrectomy
50365 Renal allotransplantation implantation graft w/ donor & recipient nephrectomy
Appendix A

Bleeding Codes
423.0 - (ICD9) HEMOPERICARDIUM
430 - (ICD9) SUBARACHNOID HEMORRHAGE
431 - (ICD9) INTRACEREBRAL HEMORRHAGE
432.0 - (ICD9) NONTRAUMATIC EXTRADURAL HEMORRHAGE
432.1 - (ICD9) SUBDURAL HEMORRHAGE
432.9 - (ICD9) UNSPECIFIED INTRACRANIAL HEMORRHAGE
459.0 - (ICD9) HEMORRHAGE UNSPECIFIED
531.0 - (ICD9) ACUTE GASTRIC ULCER WITH HEMORRHAGE
531.00 - (ICD9) ACUTE GASTRIC ULCER WITH HEMORRHAGE WITHOUT OBSTRUCTION
531.01 - (ICD9) ACUTE GASTRIC ULCER WITH HEMORRHAGE WITH OBSTRUCTION
531.2 - (ICD9) ACUTE GASTRIC ULCER WITH HEMORRHAGE AND PERFORATION
531.20 - (ICD9) ACUTE GASTRIC ULCER WITH HEMORRHAGE AND PERFORATION WITHOUT OBSTRUCTION
531.21 - (ICD9) ACUTE GASTRIC ULCER WITH HEMORRHAGE AND PERFORATION WITH OBSTRUCTION
531.4 - (ICD9) CHRONIC OR UNSPECIFIED GASTRIC ULCER WITH HEMORRHAGE
531.40 - (ICD9) CHRONIC OR UNSPECIFIED GASTRIC ULCER WITH HEMORRHAGE WITHOUT OBSTRUCTION
531.41 - (ICD9) CHRONIC OR UNSPECIFIED GASTRIC ULCER WITH HEMORRHAGE WITH OBSTRUCTION
531.6 - (ICD9) CHRONIC OR UNSPECIFIED GASTRIC ULCER WITH HEMORRHAGE AND PERFORATION
531.60 - (ICD9) CHRONIC OR UNSPECIFIED GASTRIC ULCER WITH HEMORRHAGE AND PERFORATION WITHOUT OBSTRUCTION
531.61 - (ICD9) CHRONIC OR UNSPECIFIED GASTRIC ULCER WITH HEMORRHAGE AND PERFORATION WITH OBSTRUCTION
532.0 - (ICD9) ACUTE DUODENAL ULCER WITH HEMORRHAGE
532.00 - (ICD9) ACUTE DUODENAL ULCER WITH HEMORRHAGE WITHOUT OBSTRUCTION
532.01 - (ICD9) ACUTE DUODENAL ULCER WITH HEMORRHAGE WITH OBSTRUCTION
532.2 - (ICD9) ACUTE DUODENAL ULCER WITH HEMORRHAGE AND PERFORATION
532.20 - (ICD9) ACUTE DUODENAL ULCER WITH HEMORRHAGE AND PERFORATION WITHOUT OBSTRUCTION
532.21 - (ICD9) ACUTE DUODENAL ULCER WITH HEMORRHAGE AND PERFORATION WITH OBSTRUCTION
532.4 - (ICD9) CHRONIC OR UNSPECIFIED DUODENAL ULCER WITH HEMORRHAGE
532.40 - (ICD9) CHRONIC OR UNSPECIFIED DUODENAL ULCER WITH HEMORRHAGE WITHOUT OBSTRUCTION
532.41 - (ICD9) CHRONIC OR UNSPECIFIED DUODENAL ULCER WITH HEMORRHAGE WITH OBSTRUCTION
532.6 - (ICD9) CHRONIC OR UNSPECIFIED DUODENAL ULCER WITH HEMORRHAGE AND PERFORATION
532.60 - (ICD9) CHRONIC OR UNSPECIFIED DUODENAL ULCER WITH HEMORRHAGE AND PERFORATION WITHOUT OBSTRUCTION
532.61 - (ICD9) CHRONIC OR UNSPECIFIED DUODENAL ULCER WITH HEMORRHAGE AND PERFORATION WITH OBSTRUCTION
533.0 - (ICD9) ACUTE PEPTIC ULCER OF UNSPECIFIED SITE WITH HEMORRHAGE
533.00 - (ICD9) ACUTE PEPTIC ULCER OF UNSPECIFIED SITE WITH HEMORRHAGE WITHOUT OBSTRUCTION
533.01 - (ICD9) ACUTE PEPTIC ULCER OF UNSPECIFIED SITE WITH HEMORRHAGE WITH OBSTRUCTION
533.2 - (ICD9) ACUTE PEPTIC ULCER OF UNSPECIFIED SITE WITH HEMORRHAGE AND PERFORATION
533.20 - (ICD9) ACUTE PEPTIC ULCER OF UNSPECIFIED SITE WITH HEMORRHAGE AND PERFORATION WITHOUT OBSTRUCTION
533.21 - (ICD9) ACUTE PEPTIC ULCER OF UNSPECIFIED SITE WITH HEMORRHAGE AND PERFORATION WITH OBSTRUCTION
533.4 - (ICD9) CHRONIC OR UNSPECIFIED PEPTIC ULCER OF UNSPECIFIED SITE WITH HEMORRHAGE
533.40 - (ICD9) CHRONIC OR UNSPECIFIED PEPTIC ULCER OF UNSPECIFIED SITE WITH HEMORRHAGE WITHOUT OBSTRUCTION
Appendix A

(
)
533.41 - (ICD9) CHRONIC OR UNSPECIFIED PEPTIC ULCER OF UNSPECIFIED SITE WITH HEMORRHAGE WITH OBSTRUCTION
533.6 - (ICD9) CHRONIC OR UNSPECIFIED PEPTIC ULCER OF UNSPECIFIED SITE WITH HEMORRHAGE AND PERFORATION
533.60 - (ICD9) CHRONIC OR UNSPECIFIED PEPTIC ULCER OF UNSPECIFIED SITE WITH HEMORRHAGE AND PERFORATION WITHOUT OBSTRUCTION
533.61 - (ICD9) CHRONIC OR UNSPECIFIED PEPTIC ULCER OF UNSPECIFIED SITE WITH HEMORRHAGE AND PERFORATION WITH OBSTRUCTION
534.0 - (ICD9) ACUTE GASTROJEJUNAL ULCER WITH HEMORRHAGE
534.00 - (ICD9) ACUTE GASTROJEJUNAL ULCER WITH HEMORRHAGE WITHOUT OBSTRUCTION
534.01 - (ICD9) ACUTE GASTROJEJUNAL ULCER WITH HEMORRHAGE WITH OBSTRUCTION
534.2 - (ICD9) ACUTE GASTROJEJUNAL ULCER WITH HEMORRHAGE AND PERFORATION
534.20 - (ICD9) ACUTE GASTROJEJUNAL ULCER WITH HEMORRHAGE AND PERFORATION WITHOUT OBSTRUCTION
534.21 - (ICD9) ACUTE GASTROJEJUNAL ULCER WITH HEMORRHAGE AND PERFORATION WITH OBSTRUCTION
534.4 - (ICD9) CHRONIC OR UNSPECIFIED GASTROJEJUNAL ULCER WITH HEMORRHAGE
534.40 - (ICD9) CHRONIC OR UNSPECIFIED GASTROJEJUNAL ULCER WITH HEMORRHAGE WITHOUT OBSTRUCTION
534.41 - (ICD9) CHRONIC OR UNSPECIFIED GASTROJEJUNAL ULCER WITH HEMORRHAGE WITH OBSTRUCTION
534.6 - (ICD9) CHRONIC OR UNSPECIFIED GASTROJEJUNAL ULCER WITH HEMORRHAGE AND PERFORATION
534.60 - (ICD9) CHRONIC OR UNSPECIFIED GASTROJEJUNAL ULCER WITH HEMORRHAGE AND PERFORATION WITHOUT OBSTRUCTION
534.61 - (ICD9) CHRONIC OR UNSPECIFIED GASTROJEJUNAL ULCER WITH HEMORRHAGE AND PERFORATION WITH OBSTRUCTION
562.02 - (ICD9) DIVERTICULOSIS OF SMALL INTESTINE WITH HEMORRHAGE
562.03 - (ICD9) DIVERTICULITIS OF SMALL INTESTINE WITH HEMORRHAGE
562.12 - (ICD9) DIVERTICULOSIS OF COLON WITH HEMORRHAGE
562.13 - (ICD9) DIVERTICULITIS OF COLON WITH HEMORRHAGE
568.81 - (ICD9) HEMOPERITONEUM (NONTRAUMATIC)
569.3 - (ICD9) HEMORRHAGE OF RECTUM AND ANUS
569.83 - (ICD9) PERFORATION OF INTESTINE
569.85 - (ICD9) ANGIODYSPLASIA OF INTESTINE WITH HEMORRHAGE
569.86 - (ICD9) DIEULAFOY LESION (HEMORRHAGIC) OF INTESTINE
578.0 - (ICD9) HEMATEMESIS
578.1 - (ICD9) BLOOD IN STOOL
578.9 - (ICD9) HEMORRHAGE OF GASTROINTESTINAL TRACT UNSPECIFIED
719.1 - (ICD9) HEMARTHROSIS
719.10 - (ICD9) HEMARTHROSIS SITE UNSPECIFIED
719.11 - (ICD9) HERARTHROSIS INVOLVING SHOULDER REGION
719.12 - (ICD9) HEMARTHORSIS INVOLVING UPPER ARM
719.13 - (ICD9) HEMARTHROSIS INVOLVING FOREARM
719.14 - (ICD9) HEMARTHROSIS INVOLVING HAND
719.15 - (ICD9) HEMARTHROSIS INVOLVING PELVIC REGION AND THIGH
719.16 - (ICD9) HEMARTHROSIS INVOLVING LOWER LEG
719.17 - (ICD9) HEMARTHROSIS INVOLVING ANKLE AND FOOT
719 18
(ICD9) HEMARTHROSIS INVOLVING OTHER SPECIFIED SITES
Appendix A

719.18 - (ICD9) HEMARTHROSIS INVOLVING OTHER SPECIFIED SITES
719.19 - (ICD9) HEMARTHROSIS INVOLVING MULTIPLE SITES
I31.2 - (ICD10) Hemopericardium, not elsewhere classified
I60.00 - (ICD10) Nontraumatic subarachnoid hemorrhage from unspecified carotid siphon and bifurcation
I60.01 - (ICD10) Nontraumatic subarachnoid hemorrhage from right carotid siphon and bifurcation
I60.02 - (ICD10) Nontraumatic subarachnoid hemorrhage from left carotid siphon and bifurcation
I60.10 - (ICD10) Nontraumatic subarachnoid hemorrhage from unspecified middle cerebral artery
I60.11 - (ICD10) Nontraumatic subarachnoid hemorrhage from right middle cerebral artery
I60.12 - (ICD10) Nontraumatic subarachnoid hemorrhage from left middle cerebral artery
I60.2 - (ICD10) Nontraumatic subarachnoid hemorrhage from anterior communicating artery
I60.30 - (ICD10) Nontraumatic subarachnoid hemorrhage from unspecified posterior communicating artery
I60.31 - (ICD10) Nontraumatic subarachnoid hemorrhage from right posterior communicating artery
I60.32 - (ICD10) Nontraumatic subarachnoid hemorrhage from left posterior communicating artery
I60.4 - (ICD10) Nontraumatic subarachnoid hemorrhage from basilar artery
I60.50 - (ICD10) Nontraumatic subarachnoid hemorrhage from unspecified vertebral artery
I60.51 - (ICD10) Nontraumatic subarachnoid hemorrhage from right vertebral artery
I60.52 - (ICD10) Nontraumatic subarachnoid hemorrhage from left vertebral artery
I60.6 - (ICD10) Nontraumatic subarachnoid hemorrhage from other intracranial arteries
I60.7 - (ICD10) Nontraumatic subarachnoid hemorrhage from unspecified intracranial artery
I60.8 - (ICD10) Other nontraumatic subarachnoid hemorrhage
I60.9 - (ICD10) Nontraumatic subarachnoid hemorrhage, unspecified
I61.0 - (ICD10) Nontraumatic intracerebral hemorrhage in hemisphere, subcortical
I61.1 - (ICD10) Nontraumatic intracerebral hemorrhage in hemisphere, cortical
I61.2 - (ICD10) Nontraumatic intracerebral hemorrhage in hemisphere, unspecified
I61.3 - (ICD10) Nontraumatic intracerebral hemorrhage in brain stem
I61.4 - (ICD10) Nontraumatic intracerebral hemorrhage in cerebellum
I61.5 - (ICD10) Nontraumatic intracerebral hemorrhage, intraventricular
I61.6 - (ICD10) Nontraumatic intracerebral hemorrhage, multiple localized
I61.8 - (ICD10) Other nontraumatic intracerebral hemorrhage
I61.9 - (ICD10) Nontraumatic intracerebral hemorrhage, unspecified
I62.00 - (ICD10) Nontraumatic subdural hemorrhage, unspecified
I62.01 - (ICD10) Nontraumatic acute subdural hemorrhage
I62.02 - (ICD10) Nontraumatic subacute subdural hemorrhage
I62.03 - (ICD10) Nontraumatic chronic subdural hemorrhage
I62.1 - (ICD10) Nontraumatic extradural hemorrhage
I62.9 - (ICD10) Nontraumatic intracranial hemorrhage, unspecified
K25.0 - (ICD10) Acute gastric ulcer with hemorrhage
K25.2 - (ICD10) Acute gastric ulcer with both hemorrhage and perforation
K25.4 - (ICD10) Chronic or unspecified gastric ulcer with hemorrhage
Appendix A

(
)
p
g
g
K25.6 - (ICD10) Chronic or unspecified gastric ulcer with both hemorrhage and perforation
K26.0 - (ICD10) Acute duodenal ulcer with hemorrhage
K26.2 - (ICD10) Acute duodenal ulcer with both hemorrhage and perforation
K26.4 - (ICD10) Chronic or unspecified duodenal ulcer with hemorrhage
K26.6 - (ICD10) Chronic or unspecified duodenal ulcer with both hemorrhage and perforation
K27.0 - (ICD10) Acute peptic ulcer, site unspecified, with hemorrhage
K27.2 - (ICD10) Acute peptic ulcer, site unspecified, with both hemorrhage and perforation
K27.4 - (ICD10) Chronic or unspecified peptic ulcer, site unspecified, with hemorrhage
K27.6 - (ICD10) Chronic or unspecified peptic ulcer, site unspecified, with both hemorrhage and perforation
K28.0 - (ICD10) Acute gastrojejunal ulcer with hemorrhage
K28.2 - (ICD10) Acute gastrojejunal ulcer with both hemorrhage and perforation
K28.4 - (ICD10) Chronic or unspecified gastrojejunal ulcer with hemorrhage
K28.6 - (ICD10) Chronic or unspecified gastrojejunal ulcer with both hemorrhage and perforation
K55.21 - (ICD10) Angiodysplasia of colon with hemorrhage
K56.60 - (ICD10) Unspecified intestinal obstruction
K57.01 - (ICD10) Diverticulitis of small intestine with perforation and abscess with bleeding
K57.11 - (ICD10) Diverticulosis of small intestine without perforation or abscess with bleeding
K57.13 - (ICD10) Diverticulitis of small intestine without perforation or abscess with bleeding
K57.21 - (ICD10) Diverticulitis of large intestine with perforation and abscess with bleeding
K57.31 - (ICD10) Diverticulosis of large intestine without perforation or abscess with bleeding
K57.33 - (ICD10) Diverticulitis of large intestine without perforation or abscess with bleeding
K57.41 - (ICD10) Diverticulitis of both small and large intestine with perforation and abscess with bleeding
K57.51 - (ICD10) Diverticulosis of both small and large intestine without perforation or abscess with bleeding
K57.53 - (ICD10) Diverticulitis of both small and large intestine without perforation or abscess with bleeding
K57.81 - (ICD10) Diverticulitis of intestine, part unspecified, with perforation and abscess with bleeding
K57.91 - (ICD10) Diverticulosis of intestine, part unspecified, without perforation or abscess with bleeding
K57.93 - (ICD10) Diverticulitis of intestine, part unspecified, without perforation or abscess with bleeding
K62.5 - (ICD10) Hemorrhage of anus and rectum
K63.1 - (ICD10) Perforation of intestine (nontraumatic)
K63 81
(ICD10) Di
l f
l
i
f i t
ti
Appendix A

K63.81 - (ICD10) Dieulafoy lesion of intestine
K66.1 - (ICD10) Hemoperitoneum
K92.0 - (ICD10) Hematemesis
K92.1 - (ICD10) Melena
K92.2 - (ICD10) Gastrointestinal hemorrhage, unspecified
M25.00 - (ICD10) Hemarthrosis, unspecified joint
M25.011 - (ICD10) Hemarthrosis, right shoulder
M25.012 - (ICD10) Hemarthrosis, left shoulder
M25.019 - (ICD10) Hemarthrosis, unspecified shoulder
M25.021 - (ICD10) Hemarthrosis, right elbow
M25.022 - (ICD10) Hemarthrosis, left elbow
M25.029 - (ICD10) Hemarthrosis, unspecified elbow
M25.031 - (ICD10) Hemarthrosis, right wrist
M25.032 - (ICD10) Hemarthrosis, left wrist
M25.039 - (ICD10) Hemarthrosis, unspecified wrist
M25.041 - (ICD10) Hemarthrosis, right hand
M25.042 - (ICD10) Hemarthrosis, left hand
M25.049 - (ICD10) Hemarthrosis, unspecified hand
M25.051 - (ICD10) Hemarthrosis, right hip
M25.052 - (ICD10) Hemarthrosis, left hip
M25.059 - (ICD10) Hemarthrosis, unspecified hip
Appendix A

M25.059  (ICD10) Hemarthrosis, unspecified hip
M25.061 - (ICD10) Hemarthrosis, right knee
M25.062 - (ICD10) Hemarthrosis, left knee
M25.069 - (ICD10) Hemarthrosis, unspecified knee
M25.071 - (ICD10) Hemarthrosis, right ankle
M25.072 - (ICD10) Hemarthrosis, left ankle
M25.073 - (ICD10) Hemarthrosis, unspecified ankle
M25.074 - (ICD10) Hemarthrosis, right foot
M25.075 - (ICD10) Hemarthrosis, left foot
M25.076 - (ICD10) Hemarthrosis, unspecified foot
M25.08 - (ICD10) Hemarthrosis, other specified site
R58 - (ICD10) Hemorrhage, not elsewhere classified
Legacy Attribute - Procedure Code (Any Confinement Position):
0W.3P8ZZ - (ICD10) 0W3P8ZZ, Control Bleeding in Gastrointestinal Tract, Via Natural or Artificial Opening Endoscopic
44.43 - (ICD9) ENDOSCOPIC CONTROL OF GASTRIC OR DUODENAL BLEEDING
Appendix A

HIV Treatment
Abacavir 
Amprenavir 
Atazanavir 
Darunavir 
Delavirdine 
Didanosine
Efavirenz 
Emtricitabine 
Enfuvirtide 
Etravirine 
Fosamprenavir 
Indinavir 
Lamivudine-Zidovudine
Maraviroc 
Nelfinavir 
Nevirapine 
Raltegravir 
Rilpivirine 
Ritonavir 
Ritonavir-Lopinavir                 
Saquinavir
Stavudine
Tipranavir 
Zalcitabine 
Zidovudine
Appendix A

Diabetes Medications
ALOGLIPTIN BENZOATE/PIOGLITAZONE HCL
DAPAGLIFLOZIN PROPANEDIOL
DAPAGLIFLOZIN PROPANEDIOL/SAXAGLIPTIN HCL
ERTUGLIFLOZIN PIDOLATE
EXENATIDE MICROSPHERES
INSULIN ASPART PROTAMINE HUMAN/INSULIN ASPART
INSULIN DETEMIR
INSULIN GLARGINE,HUMAN RECOMBINANT ANALOG/LIXISENATIDE
INSULIN NPH HUMAN AND INSULIN REGULAR HUMAN SEMI-SYNTHETIC
INSULIN ZINC HUMAN RECOMBINANT
LIXISENATIDE
PIOGLITAZONE HCL/GLIMEPIRIDE
REPAGLINIDE/METFORMIN HCL
ALOGLIPTIN BENZOATE
CANAGLIFLOZIN
CANAGLIFLOZIN/METFORMIN HCL
DULAGLUTIDE
INSULIN DEGLUDEC
INSULIN,PORK PURIFIED
LINAGLIPTIN
ROSIGLITAZONE MALEATE/GLIMEPIRIDE
SAXAGLIPTIN HCL/METFORMIN HCL
ALBIGLUTIDE
DAPAGLIFLOZIN PROPANEDIOL/METFORMIN HCL
ERTUGLIFLOZIN PIDOLATE/METFORMIN HCL
EXENATIDE
INSULIN ASPART
Appendix A

MIGLITOL
PRAMLINTIDE ACETATE
SEMAGLUTIDE
EMPAGLIFLOZIN
INSULIN LISPRO PROTAMINE AND INSULIN LISPRO
INSULIN ZINC EXTENDED HUMAN RECOMBINANT
SAXAGLIPTIN HCL
EMPAGLIFLOZIN/LINAGLIPTIN
ERTUGLIFLOZIN PIDOLATE/SITAGLIPTIN PHOSPHATE
INSULIN DEGLUDEC/LIRAGLUTIDE
LIRAGLUTIDE
ALOGLIPTIN BENZOATE/METFORMIN HCL
INSULIN LISPRO
EMPAGLIFLOZIN/METFORMIN HCL
LINAGLIPTIN/METFORMIN HCL
INSULIN GLARGINE,HUMAN RECOMBINANT ANALOG
NATEGLINIDE
SITAGLIPTIN PHOSPHATE
INSULIN GLULISINE
ROSIGLITAZONE MALEATE/METFORMIN HCL
SITAGLIPTIN PHOSPHATE/METFORMIN HCL
INSULIN NPH HUMAN ISOPHANE/INSULIN REGULAR, HUMAN
INSULIN REGULAR, HUMAN
GLIPIZIDE/METFORMIN HCL
PIOGLITAZONE HCL/METFORMIN HCL
REPAGLINIDE
ACETOHEXAMIDE
Appendix A

ROSIGLITAZONE MALEATE
ACARBOSE
GLYBURIDE,MICRONIZED
TOLBUTAMIDE
GLYBURIDE/METFORMIN HCL
GLIMEPIRIDE
PIOGLITAZONE HCL
TOLAZAMIDE
CHLORPROPAMIDE
GLYBURIDE
GLIPIZIDE
METFORMIN HCL
Appendix A

ACE inhibitor
Benazepril, captopril, enalapril, fosinopril, lisinopril, 
moexipril, perindopril, quinapril, ramipril, trandolapril
ARB
Azilsartan, candesartan, eprosartan, irbesartan, losartan, 
olmesartan, telmisartan, valsartan
Beta blocker
Acebutolol, atenolol, betaxolol, bisoprolol, carteolol, 
carvedilol, esmolol, labetalol, metoprolol tartrate, metoprolol 
succinate, propranolol, penbutolol, pindolol, nadolol, 
nebivolol, sotalol, timolol
Calcium channel blocker
Diltiazem, mibefradil, verapamil, amlodipine, clevidipine, 
bepridil, felodipine, isradipine, nicardipine, nifedipine, 
nimodipine, nisoldipine
Other hypertension drugs
Doxazosin, eplerenone, prazosin, terazosin, clonidine, 
guanabenz, guanadrel, guanethidine, guanfacine, 
hydralazine, methyldopa, metyrosine, reserpine, minoxidil, 
aliskiren 
Thiazides
Benzthiazide, chlorothiazide, chlorthalidone, cyclothiazide, 
hydrochlorothiazide, hydroflumethiazide, indapamide, 
methyclothiazide, metolazone, polythiazide, quinethazone, 
trichlormethiazide, bendroflumethiazide
Loop diuretics
Furosemide, bumetanide, torsemide, ethacrynic acid
Other diuretics
Amiloride, eplerenone, spironolactone, triamterene
Hypertension medications
Appendix A

Pregnancy 
Diagnosis codes 
650   NORMAL DELIVERY
660   OBSTRUCTED LABOR
661   ABNORMALITY OF FORCES OF LABOR
662   LONG LABOR
663   UMBILICAL CORD COMPLICATIONS DURING LABOR AND DELIVERY
664   TRAUMA TO PERINEUM AND VULVA DURING DELIVERY
665   OTHER OBSTETRICAL TRAUMA
667   RETAINED PLACENTA OR MEMBRANES WITHOUT HEMORRHAGE
668   COMPLICATIONS OF THE ADMINISTRATION OF ANESTHETIC OR OTHER SEDATION IN LABOR AND DELIVERY
669.94   UNSPECIFIED COMPLICATION OF LABOR AND DELIVERY POSTPARTUM CONDITION OR COMPLICATION
V24   POSTPARTUM CARE AND EXAMINATION
V24.0   POSTPARTUM CARE AND EXAMINATION IMMEDIATELY AFTER DELIVERY
V24.1   POSTPARTUM CARE AND EXAMINATION OF LACTATING MOTHER
V24.2   ROUTINE POSTPARTUM FOLLOW
V27   OUTCOME OF DELIVERY
V27.0   MOTHER WITH SINGLE LIVEBORN
V27.1   MOTHER WITH SINGLE STILLBORN+A2:J81
V27.2   MOTHER WITH TWINS BOTH LIVEBORN
V27.3   MOTHER WITH TWINS ONE LIVEBORN AND ONE STILLBORN
V27.4   MOTHER WITH TWINS BOTH STILLBORN
V27.5   MOTHER WITH OTHER MULTIPLE BIRTH ALL LIVEBORN
V27.6   MOTHER WITH OTHER MULTIPLE BIRTH SOME LIVEBORN
V27.7   MOTHER WITH OTHER MULTIPLE BIRTH ALL STILLBORN
V27.9   MOTHER WITH UNSPECIFIED OUTCOME OF DELIVERY
Procedure codes 
72.0   LOW FORCEPS OPERATION
72.1   LOW FORCEPS OPERATION WITH EPISIOTOMY
72.2   MID FORCEPS OPERATION
72.21   MID FORCEPS OPERATION WITH EPISIOTOMY
72.29   OTHER MID FORCEPS OPERATION
72.3   HIGH FORCEPS OPERATION
Appendix A

72.31   HIGH FORCEPS OPERATION WITH EPISIOTOMY
72.39   OTHER HIGH FORCEPS OPERATION
72.4   FORCEPS ROTATION OF FETAL HEAD
72.5   BREECH EXTRACTION
72.51   PARTIAL BREECH EXTRACTION WITH FORCEPS TO AFTERCOMING HEAD
72.52   OTHER PARTIAL BREECH EXTRACTION
72.53   TOTAL BREECH EXTRACTION WITH FORCEPS TO AFTERCOMING HEAD
72.54   OTHER TOTAL BREECH EXTRACTION
72.6   FORCEPS APPLICATION TO AFTERCOMING HEAD
72.7   VACUUM EXTRACTION
72.71   VACUUM EXTRACTION WITH EPISIOTOMY
72.79   OTHER VACUUM EXTRACTION
72.8   OTHER SPECIFIED INSTRUMENTAL DELIVERY
72.9   UNSPECIFIED INSTRUMENTAL DELIVERY
73.0   ARTIFICIAL RUPTURE OF MEMBRANES
73.01   INDUCTION OF LABOR BY ARTIFICIAL RUPTURE OF MEMBRANES
73.09   OTHER ARTIFICIAL RUPTURE OF MEMBRANES
73.1   OTHER SURGICAL INDUCTION OF LABOR
73.2   INTERNAL AND COMBINED VERSION AND EXTRACTION
73.21   INTERNAL AND COMBINED VERSION WITHOUT EXTRACTION
73.22   INTERNAL AND COMBINED VERSION WITH EXTRACTION
73.3   FAILED FORCEPS
73.4   MEDICAL INDUCTION OF LABOR
73.5   MANUALLY ASSISTED DELIVERY
73.51   MANUAL ROTATION OF FETAL HEAD
73.59   OTHER MANUALLY ASSISTED DELIVERY
73.6   EPISIOTOMY
73.8   OPERATIONS ON FETUS TO FACILITATE DELIVERY
73.9   OTHER OPERATIONS ASSISTING DELIVERY
73.91   EXTERNAL VERSION ASSISTING DELIVERY
73.92   REPLACEMENT OF PROLAPSED UMBILICAL CORD
73.93   INCISION OF CERVIX TO ASSIST DELIVERY
73.94   PUBIOTOMY TO ASSIST DELIVERY
73.99   OTHER OPERATIONS ASSISTING DELIVERY
74.0   CLASSICAL CESAREAN SECTION
Appendix A

74.1   LOW CERVICAL CESAREAN SECTION
74.2   EXTRAPERITONEAL CESAREAN SECTION
74.3   REMOVAL OF EXTRATUBAL ECTOPIC PREGNANCY
74.4   CESAREAN SECTION OF OTHER SPECIFIED TYPE
74.9   CESAREAN SECTION OF UNSPECIFIED TYPE
74.91   HYSTEROTOMY TO TERMINATE PREGNANCY
74.99   OTHER CESAREAN SECTION OF UNSPECIFIED TYPE
75.4   MANUAL REMOVAL OF RETAINED PLACENTA
75.5   REPAIR OF CURRENT OBSTETRIC LACERATION OF UTERUS
75.6   REPAIR OF OTHER CURRENT OBSTETRIC LACERATION
75.7   MANUAL EXPLORATION OF UTERINE CAVITY, POSTPARTUM
75.9   OTHER OBSTETRIC OPERATIONS
Appendix A

AFTER PS MATCHING
BEFORE PS MATCHING
Optum
MarketScan
Medicare
The c-statistics for the propensity score model, pre-matching was 0.861. The post-matching c-statistic 
was 0.536.
The c-statistics for the propensity score model, pre-matching was 0.85. The post-matching c-
statistic was 0.537.
The c-statistics for the propensity score model, pre-matching was 0.839. The post-matching c-statistic 
was 0.524.
Appendix B: Rivaroxaban vs Warfarin

Variable
 Reference- warfarin 
 Exposure - rivaroxaban 
(15 or 20 mg) 
St. Diff.
 Reference- warfarin 
 Exposure - rivaroxaban 
(15 or 20 mg) 
St. Diff.
 Reference- warfarin 
 Exposure - 
rivaroxaban (15 or 
St. Diff.
 Reference- warfarin 
 Exposure - rivaroxaban 
(15 or 20 mg) 
St. Diff.
Number of patients
                                          25,701                                           14,869 
32,295
                                         
17,748
                                         
92,403
                                       
40,652
                       
                                       150,399                                           73,269 
Age
...mean (sd)
76.81 (7.78)
74.48 (9.36)
0.27
76.99 (10.15)
72.74 (11.18)
0.40
79.76 (7.99)
78.49 (8.07)
0.16
78.66 (8.47)
76.28 (9.18)
0.27
...median [IQR]
78.00 [73.00, 82.00]
76.00 [69.00, 82.00]
0.23
79.00 [72.00, 84.00]
75.00 [64.00, 81.00]
0.37
80.00 [76.00, 85.00]9.00 [74.00, 84.00]
0.12
79.44 (8.47)
77.42 (9.18)
0.23
Age categories without zero category
...18 - 54; n (%)
395 (1.5%)
556 (3.7%)
-0.14
906 (2.8%)
1,010 (5.7%)
-0.14
738 (0.8%)
423 (1.0%)
-0.02
2,039 (1.4%)
1989 (2.7%)
-0.09
...55 - 64; n (%)
1,596 (6.2%)
1,657 (11.1%)
-0.17
3,653 (11.3%)
3,754 (21.2%)
-0.27
2,322 (2.5%)
1,256 (3.1%)
-0.04
7,571 (5.0%)
6,667 (9.1%)
-0.16
...65 - 74; n (%)
5,501 (21.4%)
3,823 (25.7%)
-0.10
5,619 (17.4%)
3,840 (21.6%)
-0.11
16,731 (18.1%)
9,029 (22.2%)
-0.10
27,851 (18.5%)
16,692 (22.8%)
-0.11
...>= 75; n (%)
18,209 (70.8%)
8,833 (59.4%)
0.24
22,117 (68.5%)
9,144 (51.5%)
0.35
72,612 (78.6%)
29,944 (73.7%)
0.12
112,938 (75.1%)
47,921 (65.4%)
0.21
Gender without zero category- United
...Males; n (%)
13,338 (51.9%)
7,726 (52.0%)
0.00
17,422 (53.9%)
9,827 (55.4%)
-0.03
39,860 (43.1%)
16,739 (41.2%)
0.04
70,620 (47.0%)
34,292 (46.8%)
0.00
...Females; n (%)
12,363 (48.1%)
7,143 (48.0%)
0.00
14,873 (46.1%)
7,921 (44.6%)
0.03
52,543 (56.9%)
23,913 (58.8%)
-0.04
79,779 (53.0%)
38,977 (53.2%)
0.00
Race 
...White; n (%)
85,842 (92.9%)
36,882 (90.7%)
85,842 (92.9%)
36,882 (90.7%)
0.00
...Black; n (%)
3,514 (3.8%)
1,923 (4.7%)
3,514 (3.8%)
1,923 (4.7%)
0.00
...Asian; n (%)
767 (0.8%)
513 (1.3%)
767 (0.8%)
513 (1.3%)
0.00
...Hispanic; n (%)
998 (1.1%)
596 (1.5%)
998 (1.1%)
596 (1.5%)
0.00
...North American Native; n (%)
339 (0.4%)
159 (0.4%)
339 (0.4%)
159 (0.4%)
0.00
...Other/Unknown; n (%)
943 (1.0%)
579 (1.4%)
943 (1.0%)
579 (1.4%)
0.00
Region without zero category- United v3 (lumping 
missing&other category with West)
...Northeast; n (%)
3,626 (14.1%)
2,178 (14.6%)
-0.01
7,778 (24.1%)
4,155 (23.4%)
0.02
21,665 (23.4%)
8,259 (20.3%)
0.08
33,069 (22.0%)
14,592 (19.9%)
0.05
...South; n (%)
8,341 (32.5%)
6,178 (41.5%)
-0.19
10,408 (32.2%)
4,919 (27.7%)
0.10
28,585 (30.9%)
16,109 (39.6%)
-0.18
47,334 (31.5%)
27,206 (37.1%)
-0.12
...Midwest; n (%)
5,845 (22.7%)
2,875 (19.3%)
0.08
8,928 (27.6%)
6,242 (35.2%)
-0.16
27,907 (30.2%)
10,396 (25.6%)
0.10
42,680 (28.4%)
19,513 (26.6%)
0.04
...West; n (%)
7,889 (30.7%)
3,638 (24.5%)
0.14
5,055 (15.7%)
2,317 (13.1%)
0.07
14,246 (15.4%)
5,888 (14.5%)
0.03
27,190 (18.1%)
11,843 (16.2%)
0.05
...Unknown+missing; n (%)
N/A
N/A
#VALUE!
126 (0.4%)
115 (0.6%)
-0.03
N/A
N/A
#VALUE!
126 (0.4%)
115 (0.6%)
-0.03
CV Covariates
Ischemic heart disease; n (%)
9,344 (36.4%)
5,576 (37.5%)
-0.02
11,325 (35.1%)
6,317 (35.6%)
-0.01
37,684 (40.8%)
17,950 (44.2%)
-0.07
58,353 (38.8%)
29,843 (40.7%)
-0.04
Acute MI; n (%)
682 (2.7%)
450 (3.0%)
-0.02
729 (2.3%)
476 (2.7%)
-0.03
2,949 (3.2%)
1,572 (3.9%)
-0.04
4360 (2.9%)
2498 (3.4%)
-0.03
ACS/unstable angina; n (%)
582 (2.3%)
465 (3.1%)
-0.05
680 (2.1%)
509 (2.9%)
-0.05
2,657 (2.9%)
1,599 (3.9%)
-0.06
3919 (2.6%)
2573 (3.5%)
-0.05
Old MI; n (%)
1,268 (4.9%)
859 (5.8%)
-0.04
949 (2.9%)
543 (3.1%)
-0.01
6,575 (7.1%)
3,525 (8.7%)
-0.06
8792 (5.8%)
4927 (6.7%)
-0.04
Stable angina; n (%)
1,103 (4.3%)
862 (5.8%)
-0.07
1,016 (3.1%)
756 (4.3%)
-0.06
3,424 (3.7%)
2,051 (5.0%)
-0.06
5,543 (3.7%)
3,669 (5.0%)
-0.06
Coronary atherosclerosis and other forms of chronic 
ischemic heart disease; n (%)
8,620 (33.5%)
5,100 (34.3%)
-0.02
10,565 (32.7%)
5,774 (32.5%)
0.00
35,060 (37.9%)
16,501 (40.6%)
-0.06
54,245 (36.1%)
27,375 (37.4%)
-0.03
Other atherosclerosis with ICD10 v2 Copy; n (%)
459 (1.8%)
229 (1.5%)
0.02
612 (1.9%)
282 (1.6%)
0.02
1,748 (1.9%)
698 (1.7%)
0.02
2819 (1.9%)
1209 (1.7%)
0.02
Previous cardiac procedure (CABG or PTCA or Stent) 
v4; n (%)
210 (0.8%)
147 (1.0%)
-0.02
294 (0.9%)
131 (0.7%)
0.02
1,098 (1.2%)
509 (1.3%)
-0.01
1602 (1.1%)
787 (1.1%)
0.00
History of CABG or PTCA; n (%)
2,059 (8.0%)
1,491 (10.0%)
-0.07
1,375 (4.3%)
879 (5.0%)
-0.03
12,032 (13.0%)
6,338 (15.6%)
-0.07
15,466 (10.3%)
8,708 (11.9%)
-0.05
Any stroke; n (%)
4,563 (17.8%)
3,218 (21.6%)
-0.10
5,295 (16.4%)
3,292 (18.5%)
-0.06
18,172 (19.7%)
9,000 (22.1%)
-0.06
28,030 (18.6%)
15,510 (21.2%)
-0.07
Ischemic stroke (w and w/o mention of cerebral 
infarction); n (%)
4,563 (17.8%)
3,218 (21.6%)
-0.10
5,295 (16.4%)
3,292 (18.5%)
-0.06
18,114 (19.6%)
8,981 (22.1%)
-0.06
27,972 (18.6%)
15,491 (21.1%)
-0.06
Hemorrhagic stroke; n (%)
0 (0.0%)
0 (0.0%)
#DIV/0!
0 (0.0%)
0 (0.0%)
#DIV/0!
226 (0.2%)
97 (0.2%)
0.00
226 (0.2%)
97 (0.1%)
0.03
TIA; n (%)
1,646 (6.4%)
1,300 (8.7%)
-0.09
1,863 (5.8%)
1,452 (8.2%)
-0.09
5,231 (5.7%)
2,791 (6.9%)
-0.05
8740 (5.8%)
5543 (7.6%)
-0.07
Other cerebrovascular disease; n (%)
887 (3.5%)
674 (4.5%)
-0.05
944 (2.9%)
581 (3.3%)
-0.02
4,120 (4.5%)
2,059 (5.1%)
-0.03
5951 (4.0%)
3314 (4.5%)
-0.02
Late effects of cerebrovascular disease; n (%)
992 (3.9%)
563 (3.8%)
0.01
948 (2.9%)
445 (2.5%)
0.02
5,242 (5.7%)
2,344 (5.8%)
0.00
7182 (4.8%)
3352 (4.6%)
0.01
Cerebrovascular procedure; n (%)
36 (0.1%)
24 (0.2%)
-0.03
56 (0.2%)
32 (0.2%)
0.00
255 (0.3%)
138 (0.3%)
0.00
347 (0.2%)
194 (0.3%)
-0.02
Heart failure (CHF); n (%)
6,985 (27.2%)
3,669 (24.7%)
0.06
8,000 (24.8%)
3,790 (21.4%)
0.08
33,361 (36.1%)
15,107 (37.2%)
-0.02
48,346 (32.1%)
22,566 (30.8%)
0.03
Peripheral Vascular Disease (PVD) or PVD Surgery v2; 
n (%)
2,542 (9.9%)
1,530 (10.3%)
-0.01
2,939 (9.1%)
1,390 (7.8%)
0.05
10,824 (11.7%)
4,854 (11.9%)
-0.01
16,305 (10.8%)
7,774 (10.6%)
0.01
Atrial fibrillation; n (%)
24,905 (96.9%)
14,554 (97.9%)
-0.06
30,559 (94.6%)
17,422 (98.2%)
-0.19
89,565 (96.9%)
39,491 (97.1%)
-0.01
145,029 (96.4%)
71,467 (97.5%)
-0.06
Other cardiac dysrhythmia; n (%)
13,569 (52.8%)
10,907 (73.4%)
-0.44
10,549 (32.7%)
8,843 (49.8%)
-0.35
44,238 (47.9%)
24,562 (60.4%)
-0.25
68,356 (45.4%)
44,312 (60.5%)
-0.31
Cardiac conduction disorders; n (%)
2,156 (8.4%)
1,560 (10.5%)
-0.07
2,075 (6.4%)
1,362 (7.7%)
-0.05
8,105 (8.8%)
4,354 (10.7%)
-0.06
12336 (8.2%)
7276 (9.9%)
-0.06
Other CVD; n (%)
8,898 (34.6%)
5,631 (37.9%)
-0.07
10,301 (31.9%)
6,111 (34.4%)
-0.05
32,880 (35.6%)
15,926 (39.2%)
-0.07
52,079 (34.6%)
27,668 (37.8%)
-0.07
Diabetes-related complications
Diabetic retinopathy; n (%)
509 (2.0%)
251 (1.7%)
0.02
567 (1.8%)
234 (1.3%)
0.04
1,748 (1.9%)
714 (1.8%)
0.01
2,824 (1.9%)
1,199 (1.6%)
0.02
Diabetes with other ophthalmic manifestations; n 
(%)
38 (0.1%)
37 (0.2%)
-0.03
433 (1.3%)
168 (0.9%)
0.04
1,127 (1.2%)
458 (1.1%)
0.01
1598 (1.1%)
663 (0.9%)
0.02
Retinal detachment, vitreous hemorrhage, 
vitrectomy; n (%)
48 (0.2%)
35 (0.2%)
0.00
81 (0.3%)
35 (0.2%)
0.02
175 (0.2%)
76 (0.2%)
0.00
304 (0.2%)
146 (0.2%)
0.00
Retinal laser coagulation therapy; n (%)
33 (0.1%)
14 (0.1%)
0.00
84 (0.3%)
27 (0.2%)
0.02
179 (0.2%)
76 (0.2%)
0.00
296 (0.2%)
117 (0.2%)
0.00
Occurrence of Diabetic Neuropathy v2 Copy; n (%)
1,737 (6.8%)
892 (6.0%)
0.03
1,633 (5.1%)
840 (4.7%)
0.02
6,290 (6.8%)
2,868 (7.1%)
-0.01
9660 (6.4%)
4600 (6.3%)
0.00
Unmatched
Optum
MarketScan
Medicare
POOLED
Appendix B: Rivaroxaban vs Warfarin

Occurrence of diabetic nephropathy V3 with ICD10 
Copy; n (%)
0 (0.0%)
0 (0.0%)
#DIV/0!
0 (0.0%)
0 (0.0%)
#DIV/0!
1,264 (1.4%)
565 (1.4%)
0.00
1,264 (0.8%)
565 (0.8%)
0.00
Hypoglycemia v2; n (%)
267 (1.0%)
118 (0.8%)
0.02
460 (1.4%)
194 (1.1%)
0.03
2,229 (2.4%)
1,198 (2.9%)
-0.03
2956 (2.0%)
1510 (2.1%)
-0.01
Hyperglycemia; n (%)
1,205 (4.7%)
912 (6.1%)
-0.06
701 (2.2%)
569 (3.2%)
-0.06
4,983 (5.4%)
2,695 (6.6%)
-0.05
6889 (4.6%)
4176 (5.7%)
-0.05
Disorders of fluid electrolyte and acid-base balance; n 
(%)
2,379 (9.3%)
1,624 (10.9%)
-0.05
2,276 (7.0%)
1,498 (8.4%)
-0.05
11,714 (12.7%)
5,125 (12.6%)
0.00
16369 (10.9%)
8247 (11.3%)
-0.01
Diabetic ketoacidosis; n (%)
28 (0.1%)
24 (0.2%)
-0.03
35 (0.1%)
24 (0.1%)
0.00
168 (0.2%)
81 (0.2%)
0.00
231 (0.2%)
129 (0.2%)
0.00
Hyperosmolar hyperglycemic nonketotic syndrome 
(HONK); n (%)
26 (0.1%)
23 (0.2%)
-0.03
25 (0.1%)
19 (0.1%)
0.00
147 (0.2%)
86 (0.2%)
0.00
198 (0.1%)
128 (0.2%)
-0.03
Diabetes with peripheral circulatory disorders with 
ICD-10 v2 Copy; n (%)
863 (3.4%)
413 (2.8%)
0.03
810 (2.5%)
339 (1.9%)
0.04
4,632 (5.0%)
1,893 (4.7%)
0.01
6305 (4.2%)
2645 (3.6%)
0.03
Diabetic Foot; n (%)
641 (2.5%)
259 (1.7%)
0.06
864 (2.7%)
329 (1.9%)
0.05
4,161 (4.5%)
1,511 (3.7%)
0.04
5666 (3.8%)
2099 (2.9%)
0.05
Gangrene v2; n (%)
32 (0.1%)
25 (0.2%)
-0.03
53 (0.2%)
14 (0.1%)
0.03
251 (0.3%)
80 (0.2%)
0.02
336 (0.2%)
119 (0.2%)
0.00
Lower extremity amputation; n (%)
103 (0.4%)
47 (0.3%)
0.02
66 (0.2%)
33 (0.2%)
0.00
577 (0.6%)
221 (0.5%)
0.01
746 (0.5%)
301 (0.4%)
0.01
Osteomyelitis; n (%)
89 (0.3%)
43 (0.3%)
0.00
130 (0.4%)
65 (0.4%)
0.00
642 (0.7%)
264 (0.6%)
0.01
861 (0.6%)
372 (0.5%)
0.01
Skin infections v2; n (%)
1,508 (5.9%)
777 (5.2%)
0.03
2,170 (6.7%)
1,006 (5.7%)
0.04
7,041 (7.6%)
2,925 (7.2%)
0.02
10719 (7.1%)
4708 (6.4%)
0.03
Erectile dysfunction; n (%)
400 (1.6%)
301 (2.0%)
-0.03
363 (1.1%)
327 (1.8%)
-0.06
577 (0.6%)
320 (0.8%)
-0.02
1340 (0.9%)
948 (1.3%)
-0.04
Diabetes with unspecified complication; n (%)
345 (1.3%)
282 (1.9%)
-0.05
355 (1.1%)
254 (1.4%)
-0.03
1,374 (1.5%)
754 (1.9%)
-0.03
2074 (1.4%)
1290 (1.8%)
-0.03
Diabetes mellitus without mention of complications; 
n (%)
9,288 (36.1%)
5,120 (34.4%)
0.04
10,733 (33.2%)
6,006 (33.8%)
-0.01
40,275 (43.6%)
18,008 (44.3%)
-0.01
60,296 (40.1%)
29,134 (39.8%)
0.01
Hypertension: 1 inpatient or 2 outpatient claims 
within 365 days; n (%)
21,744 (84.6%)
12,927 (86.9%)
-0.07
23,292 (72.1%)
14,059 (79.2%)
-0.17
85,616 (92.7%)
38,411 (94.5%)
-0.07
130,652 (86.9%)
65,397 (89.3%)
-0.07
Hyperlipidemia v2; n (%)
15,725 (61.2%)
9,844 (66.2%)
-0.10
14,454 (44.8%)
9,966 (56.2%)
-0.23
53,237 (57.6%)
26,192 (64.4%)
-0.14
83,416 (55.5%)
46,002 (62.8%)
-0.15
Edema; n (%)
2,694 (10.5%)
1,703 (11.5%)
-0.03
2,678 (8.3%)
1,441 (8.1%)
0.01
10,081 (10.9%)
4,546 (11.2%)
-0.01
15453 (10.3%)
7690 (10.5%)
-0.01
Renal Dysfunction (non-diabetic) v2; n (%)
17 (0.1%)
7 (0.0%)
0.04
19 (0.1%)
12 (0.1%)
0.00
4,118 (4.5%)
1,550 (3.8%)
0.04
4,154 (2.8%)
1,569 (2.1%)
0.05
Occurrence of acute renal disease v2; n (%)
13 (0.1%)
6 (0.0%)
0.04
19 (0.1%)
12 (0.1%)
0.00
466 (0.5%)
199 (0.5%)
0.00
498 (0.3%)
217 (0.3%)
0.00
Occurrence of chronic renal insufficiency; n (%)
0 (0.0%)
0 (0.0%)
#DIV/0!
0 (0.0%)
0 (0.0%)
#DIV/0!
2,595 (2.8%)
832 (2.0%)
0.05
2,595 (1.7%)
832 (1.1%)
0.05
Chronic kidney disease v2; n (%)
0 (0.0%)
0 (0.0%)
#DIV/0!
0 (0.0%)
0 (0.0%)
#DIV/0!
2,451 (2.7%)
775 (1.9%)
0.05
2,451 (1.6%)
775 (1.1%)
0.04
CKD Stage 3-4; n (%)
0 (0.0%)
0 (0.0%)
#DIV/0!
0 (0.0%)
0 (0.0%)
#DIV/0!
1,885 (2.0%)
538 (1.3%)
0.05
1,885 (1.3%)
538 (0.7%)
0.06
Occurrence of hypertensive nephropathy; n (%)
0 (0.0%)
0 (0.0%)
#DIV/0!
0 (0.0%)
0 (0.0%)
#DIV/0!
530 (0.6%)
239 (0.6%)
0.00
#VALUE!
239 (0.3%)
#VALUE!
Occurrence of miscellaneous renal insufficiency v2; n 
(%)
1 (0.0%)
1 (0.0%)
#DIV/0!
0 (0.0%)
0 (0.0%)
#DIV/0!
1,435 (1.6%)
642 (1.6%)
0.00
1,436 (1.0%)
643 (0.9%)
0.01
Glaucoma or cataracts v2; n (%)
5,562 (21.6%)
3,146 (21.2%)
0.01
7,173 (22.2%)
3,770 (21.2%)
0.02
1,558 (1.7%)
741 (1.8%)
-0.01
14,293 (9.5%)
7,657 (10.5%)
-0.03
Cellulitis or abscess of toe; n (%)
337 (1.3%)
241 (1.6%)
-0.03
280 (0.9%)
179 (1.0%)
-0.01
3,729 (4.0%)
1,328 (3.3%)
0.04
4346 (2.9%)
1748 (2.4%)
0.03
Foot ulcer; n (%)
650 (2.5%)
262 (1.8%)
0.05
891 (2.8%)
336 (1.9%)
0.06
78 (0.1%)
47 (0.1%)
0.00
1619 (1.1%)
645 (0.9%)
0.02
Bladder stones; n (%)
23 (0.1%)
12 (0.1%)
0.00
28 (0.1%)
15 (0.1%)
0.00
1,249 (1.4%)
656 (1.6%)
-0.02
1300 (0.9%)
683 (0.9%)
0.00
Kidney stones; n (%)
197 (0.8%)
170 (1.1%)
-0.03
297 (0.9%)
201 (1.1%)
-0.02
14,547 (15.7%)
6,671 (16.4%)
-0.02
15041 (10.0%)
7042 (9.6%)
0.01
Urinary tract infections (UTIs); n (%)
2,316 (9.0%)
1,299 (8.7%)
0.01
2,410 (7.5%)
1,240 (7.0%)
0.02
33,456 (36.2%)
16,172 (39.8%)
-0.07
38,182 (25.4%)
18,711 (25.5%)
0.00
Dipstick urinalysis; n (%)
6,881 (26.8%)
4,590 (30.9%)
-0.09
6,443 (20.0%)
4,127 (23.3%)
-0.08
14,331 (15.5%)
6,373 (15.7%)
-0.01
27,655 (18.4%)
15,090 (20.6%)
-0.06
Non-dipstick urinalysis; n (%)
3,469 (13.5%)
2,020 (13.6%)
0.00
1,948 (6.0%)
1,256 (7.1%)
-0.04
3,642 (3.9%)
1,643 (4.0%)
-0.01
9,059 (6.0%)
4,919 (6.7%)
-0.03
Urine function test; n (%)
661 (2.6%)
362 (2.4%)
0.01
1,148 (3.6%)
580 (3.3%)
0.02
1,909 (2.1%)
900 (2.2%)
-0.01
3718 (2.5%)
1842 (2.5%)
0.00
Cytology; n (%)
219 (0.9%)
155 (1.0%)
-0.01
382 (1.2%)
167 (0.9%)
0.03
1,916 (2.1%)
842 (2.1%)
0.00
2517 (1.7%)
1164 (1.6%)
0.01
Cystoscopy; n (%)
257 (1.0%)
131 (0.9%)
0.01
504 (1.6%)
210 (1.2%)
0.03
#REF!
#REF!
#REF!
#REF!
#REF!
#REF!
Other Covariates
Liver disease; n (%)
0 (0.0%)
0 (0.0%)
#DIV/0!
0 (0.0%)
0 (0.0%)
#DIV/0!
938 (1.0%)
501 (1.2%)
-0.02
938 (0.6%)
501 (0.7%)
-0.01
Osteoarthritis; n (%)
4,861 (18.9%)
3,135 (21.1%)
-0.06
5,140 (15.9%)
3,000 (16.9%)
-0.03
20,522 (22.2%)
10,442 (25.7%)
-0.08
30523 (20.3%)
16577 (22.6%)
-0.06
Other arthritis, arthropathies and musculoskeletal 
pain; n (%)
9,456 (36.8%)
6,010 (40.4%)
-0.07
11,557 (35.8%)
6,608 (37.2%)
-0.03
37,694 (40.8%)
17,578 (43.2%)
-0.05
58707 (39.0%)
30196 (41.2%)
-0.04
Dorsopathies; n (%)
5,242 (20.4%)
3,469 (23.3%)
-0.07
5,958 (18.4%)
3,826 (21.6%)
-0.08
20,625 (22.3%)
10,095 (24.8%)
-0.06
31825 (21.2%)
17390 (23.7%)
-0.06
Fractures; n (%)
1,067 (4.2%)
569 (3.8%)
0.02
1,475 (4.6%)
655 (3.7%)
0.05
5,670 (6.1%)
2,346 (5.8%)
0.01
8212 (5.5%)
3570 (4.9%)
0.03
Falls v2; n (%)
1,290 (5.0%)
750 (5.0%)
0.00
625 (1.9%)
333 (1.9%)
0.00
2,916 (3.2%)
1,273 (3.1%)
0.01
4831 (3.2%)
2356 (3.2%)
0.00
Osteoporosis; n (%)
2,120 (8.2%)
1,174 (7.9%)
0.01
2,196 (6.8%)
977 (5.5%)
0.05
9,398 (10.2%)
4,284 (10.5%)
-0.01
13714 (9.1%)
6435 (8.8%)
0.01
Hyperthyroidism; n (%)
301 (1.2%)
190 (1.3%)
-0.01
262 (0.8%)
192 (1.1%)
-0.03
1,116 (1.2%)
562 (1.4%)
-0.02
1679 (1.1%)
944 (1.3%)
-0.02
Hypothyroidism v2; n (%)
4,578 (17.8%)
2,866 (19.3%)
-0.04
3,919 (12.1%)
2,552 (14.4%)
-0.07
14,603 (15.8%)
5,985 (14.7%)
0.03
23100 (15.4%)
11403 (15.6%)
-0.01
Other disorders of thyroid gland V2; n (%)
785 (3.1%)
608 (4.1%)
-0.05
861 (2.7%)
677 (3.8%)
-0.06
3,132 (3.4%)
1,569 (3.9%)
-0.03
4778 (3.2%)
2854 (3.9%)
-0.04
Depression; n (%)
1,966 (7.6%)
1,253 (8.4%)
-0.03
1,876 (5.8%)
1,092 (6.2%)
-0.02
9,551 (10.3%)
4,998 (12.3%)
-0.06
13393 (8.9%)
7343 (10.0%)
-0.04
Anxiety; n (%)
1,921 (7.5%)
1,548 (10.4%)
-0.10
1,417 (4.4%)
1,206 (6.8%)
-0.10
7,883 (8.5%)
4,932 (12.1%)
-0.12
11221 (7.5%)
7686 (10.5%)
-0.10
Sleep_Disorder; n (%)
2,242 (8.7%)
1,139 (7.7%)
0.04
3,395 (10.5%)
2,017 (11.4%)
-0.03
8,029 (8.7%)
3,474 (8.5%)
0.01
13666 (9.1%)
6630 (9.0%)
0.00
Dementia; n (%)
1,801 (7.0%)
1,125 (7.6%)
-0.02
1,911 (5.9%)
830 (4.7%)
0.05
8,977 (9.7%)
4,265 (10.5%)
-0.03
12689 (8.4%)
6220 (8.5%)
0.00
Delirium; n (%)
416 (1.6%)
261 (1.8%)
-0.02
521 (1.6%)
228 (1.3%)
0.03
2,706 (2.9%)
1,367 (3.4%)
-0.03
3643 (2.4%)
1856 (2.5%)
-0.01
Psychosis; n (%)
319 (1.2%)
176 (1.2%)
0.00
441 (1.4%)
190 (1.1%)
0.03
2,089 (2.3%)
961 (2.4%)
-0.01
2849 (1.9%)
1327 (1.8%)
0.01
Obesity; n (%)
2,962 (11.5%)
2,712 (18.2%)
-0.19
2,363 (7.3%)
2,324 (13.1%)
-0.19
11,623 (12.6%)
6,894 (17.0%)
-0.12
16948 (11.3%)
11930 (16.3%)
-0.15
Overweight; n (%)
887 (3.5%)
894 (6.0%)
-0.12
356 (1.1%)
426 (2.4%)
-0.10
2,338 (2.5%)
1,512 (3.7%)
-0.07
3581 (2.4%)
2832 (3.9%)
-0.09
Smoking; n (%)
3,155 (12.3%)
2,794 (18.8%)
-0.18
1,598 (4.9%)
1,423 (8.0%)
-0.13
19,504 (21.1%)
11,882 (29.2%)
-0.19
24257 (16.1%)
16099 (22.0%)
-0.15
Alcohol abuse or dependence; n (%)
0 (0.0%)
0 (0.0%)
#DIV/0!
0 (0.0%)
0 (0.0%)
#DIV/0!
51 (0.1%)
32 (0.1%)
0.00
51 (0.0%)
32 (0.0%)
#DIV/0!
Drug abuse or dependence; n (%)
0 (0.0%)
0 (0.0%)
#DIV/0!
0 (0.0%)
0 (0.0%)
#DIV/0!
123 (0.1%)
108 (0.3%)
-0.04
123 (0.1%)
108 (0.1%)
0.00
Appendix B: Rivaroxaban vs Warfarin

COPD; n (%)
4,309 (16.8%)
2,430 (16.3%)
0.01
4,571 (14.2%)
2,352 (13.3%)
0.03
18,074 (19.6%)
8,952 (22.0%)
-0.06
26954 (17.9%)
13734 (18.7%)
-0.02
Asthma; n (%)
1,542 (6.0%)
1,081 (7.3%)
-0.05
1,625 (5.0%)
1,171 (6.6%)
-0.07
6,360 (6.9%)
3,495 (8.6%)
-0.06
9527 (6.3%)
5747 (7.8%)
-0.06
Obstructive sleep apnea; n (%)
2,457 (9.6%)
1,923 (12.9%)
-0.10
2,936 (9.1%)
2,260 (12.7%)
-0.12
7,564 (8.2%)
4,077 (10.0%)
-0.06
12957 (8.6%)
8260 (11.3%)
-0.09
Pneumonia; n (%)
1,531 (6.0%)
901 (6.1%)
0.00
1,914 (5.9%)
1,034 (5.8%)
0.00
8,764 (9.5%)
4,313 (10.6%)
-0.04
12209 (8.1%)
6248 (8.5%)
-0.01
Imaging; n (%)
36 (0.1%)
27 (0.2%)
-0.03
44 (0.1%)
15 (0.1%)
0.00
3,729 (4.0%)
1,328 (3.3%)
0.04
3809 (2.5%)
1370 (1.9%)
0.04
Other Medications
Use of ACE inhibitors; n (%)
9,773 (38.0%)
5,230 (35.2%)
0.06
11,540 (35.7%)
6,215 (35.0%)
0.01
35,261 (38.2%)
15,477 (38.1%)
0.00
56574 (37.6%)
26922 (36.7%)
0.02
Use of ARBs; n (%)
5,359 (20.9%)
3,889 (26.2%)
-0.13
7,683 (23.8%)
4,892 (27.6%)
-0.09
20,854 (22.6%)
10,920 (26.9%)
-0.10
33896 (22.5%)
19701 (26.9%)
-0.10
Use of Loop Diuretics - United; n (%)
7,760 (30.2%)
3,674 (24.7%)
0.12
10,702 (33.1%)
3,963 (22.3%)
0.24
40,069 (43.4%)
15,255 (37.5%)
0.12
58531 (38.9%)
22892 (31.2%)
0.16
Use of other diuretics- United; n (%)
1,535 (6.0%)
731 (4.9%)
0.05
2,341 (7.2%)
878 (4.9%)
0.10
7,877 (8.5%)
2,806 (6.9%)
0.06
11753 (7.8%)
4415 (6.0%)
0.07
Use of nitrates-United; n (%)
2,055 (8.0%)
1,038 (7.0%)
0.04
3,094 (9.6%)
1,354 (7.6%)
0.07
10,921 (11.8%)
4,642 (11.4%)
0.01
16070 (10.7%)
7034 (9.6%)
0.04
Use of other hypertension drugs; n (%)
2,028 (7.9%)
1,125 (7.6%)
0.01
2,574 (8.0%)
1,303 (7.3%)
0.03
7,958 (8.6%)
3,455 (8.5%)
0.00
12560 (8.4%)
5883 (8.0%)
0.01
Use of digoxin- United; n (%)
4,005 (15.6%)
1,311 (8.8%)
0.21
6,378 (19.7%)
1,975 (11.1%)
0.24
17,796 (19.3%)
5,477 (13.5%)
0.16
28179 (18.7%)
8763 (12.0%)
0.19
Use of Anti-arrhythmics; n (%)
2,453 (9.5%)
2,071 (13.9%)
-0.14
3,881 (12.0%)
2,847 (16.0%)
-0.12
10,257 (11.1%)
6,110 (15.0%)
-0.12
16591 (11.0%)
11028 (15.1%)
-0.12
Use of COPD/asthma meds- United; n (%)
4,206 (16.4%)
2,858 (19.2%)
-0.07
5,916 (18.3%)
3,513 (19.8%)
-0.04
18,597 (20.1%)
9,406 (23.1%)
-0.07
28719 (19.1%)
15777 (21.5%)
-0.06
Use of statins; n (%)
15,187 (59.1%)
9,008 (60.6%)
-0.03
19,252 (59.6%)
10,616 (59.8%)
0.00
56,100 (60.7%)
25,111 (61.8%)
-0.02
90539 (60.2%)
44735 (61.1%)
-0.02
Use of other lipid-lowering drugs; n (%)
1,698 (6.6%)
959 (6.4%)
0.01
3,164 (9.8%)
1,658 (9.3%)
0.02
6,803 (7.4%)
2,989 (7.4%)
0.00
11665 (7.8%)
5606 (7.7%)
0.00
Use of antiplatelet agents; n (%)
2,667 (10.4%)
2,234 (15.0%)
-0.14
4,187 (13.0%)
2,985 (16.8%)
-0.11
12,151 (13.2%)
7,088 (17.4%)
-0.12
19005 (12.6%)
12307 (16.8%)
-0.12
Use of heparin and other low-molecular weight 
heparins; n (%)
1,027 (4.0%)
48 (0.3%)
0.26
13 (0.0%)
2 (0.0%)
#DIV/0!
5,378 (5.8%)
271 (0.7%)
0.29
6418 (4.3%)
321 (0.4%)
0.26
Use of NSAIDs; n (%)
2,211 (8.6%)
1,854 (12.5%)
-0.13
2,679 (8.3%)
2,192 (12.4%)
-0.13
8,445 (9.1%)
5,496 (13.5%)
-0.14
13335 (8.9%)
9542 (13.0%)
-0.13
Use of oral corticosteroids; n (%)
4,525 (17.6%)
3,114 (20.9%)
-0.08
5,871 (18.2%)
3,585 (20.2%)
-0.05
20,413 (22.1%)
10,417 (25.6%)
-0.08
30809 (20.5%)
17116 (23.4%)
-0.07
Use of bisphosphonate (United); n (%)
1,032 (4.0%)
504 (3.4%)
0.03
1,328 (4.1%)
488 (2.7%)
0.08
3,634 (3.9%)
1,530 (3.8%)
0.01
5994 (4.0%)
2522 (3.4%)
0.03
Use of opioids- United; n (%)
5,799 (22.6%)
3,261 (21.9%)
0.02
7,739 (24.0%)
4,176 (23.5%)
0.01
25,851 (28.0%)
11,903 (29.3%)
-0.03
39389 (26.2%)
19340 (26.4%)
0.00
Use of antidepressants; n (%)
4,895 (19.0%)
3,065 (20.6%)
-0.04
6,023 (18.6%)
3,323 (18.7%)
0.00
22,801 (24.7%)
10,978 (27.0%)
-0.05
33719 (22.4%)
17366 (23.7%)
-0.03
Use of antipsychotics; n (%)
375 (1.5%)
238 (1.6%)
-0.01
504 (1.6%)
250 (1.4%)
0.02
2,418 (2.6%)
1,335 (3.3%)
-0.04
3297 (2.2%)
1823 (2.5%)
-0.02
Use of anticonvulsants; n (%)
2,989 (11.6%)
1,777 (12.0%)
-0.01
3,445 (10.7%)
1,742 (9.8%)
0.03
13,599 (14.7%)
6,653 (16.4%)
-0.05
20033 (13.3%)
10172 (13.9%)
-0.02
Use of lithium- United; n (%)
13 (0.1%)
12 (0.1%)
0.00
23 (0.1%)
18 (0.1%)
0.00
29 (0.0%)
30 (0.1%)
-0.04
65 (0.0%)
60 (0.1%)
-0.04
Use of Benzos- United; n (%)
2,295 (8.9%)
1,810 (12.2%)
-0.11
4,007 (12.4%)
2,389 (13.5%)
-0.03
10,742 (11.6%)
6,233 (15.3%)
-0.11
17044 (11.3%)
10432 (14.2%)
-0.09
Use of anxiolytics/hypnotics- United; n (%)
1,231 (4.8%)
865 (5.8%)
-0.04
2,019 (6.3%)
1,221 (6.9%)
-0.02
5,918 (6.4%)
3,005 (7.4%)
-0.04
9168 (6.1%)
5091 (6.9%)
-0.03
Use of dementia meds- United; n (%)
988 (3.8%)
571 (3.8%)
0.00
1,481 (4.6%)
546 (3.1%)
0.08
5,159 (5.6%)
2,315 (5.7%)
0.00
7628 (5.1%)
3432 (4.7%)
0.02
Use of antiparkinsonian meds- United; n (%)
695 (2.7%)
399 (2.7%)
0.00
923 (2.9%)
441 (2.5%)
0.02
3,529 (3.8%)
1,659 (4.1%)
-0.02
5147 (3.4%)
2499 (3.4%)
0.00
Any use of pramlintide; n (%)
3 (0.0%)
3 (0.0%)
#DIV/0!
4 (0.0%)
2 (0.0%)
#DIV/0!
**
**
#VALUE!
#VALUE!
#VALUE!
#VALUE!
Any use of 1st generation sulfonylureas; n (%)
1 (0.0%)
0 (0.0%)
#DIV/0!
14 (0.0%)
1 (0.0%)
#DIV/0!
**
**
#VALUE!
#VALUE!
#VALUE!
0.00
Entresto (sacubitril/valsartan); n (%)
64 (0.2%)
67 (0.5%)
-0.05
18 (0.1%)
29 (0.2%)
-0.03
87 (0.1%)
88 (0.2%)
-0.03
169 (0.1%)
184 (0.3%)
0.00
Labs
                                          57,996                                           32,617 
Lab values- HbA1c (%) v3; n (%)
3,444 (13.4%)
2,695 (18.1%)
-0.13
456 (1.4%)
242 (1.4%)
0.00
N/A
N/A
#VALUE!
3,900 (6.7%)
2,937 (9.0%)
-0.09
Lab values- HbA1c (%) (within 3 months) v3; n (%)
2,217 (8.6%)
1,747 (11.7%)
-0.10
321 (1.0%)
170 (1.0%)
0.00
N/A
N/A
#VALUE!
2,538 (4.4%)
1,917 (5.9%)
-0.07
Lab values- HbA1c (%) (within 6 months) v3; n (%)
3,444 (13.4%)
2,695 (18.1%)
-0.13
456 (1.4%)
242 (1.4%)
0.00
N/A
N/A
#VALUE!
3,900 (6.7%)
2,937 (9.0%)
-0.09
Lab values- BNP; n (%)
401 (1.6%)
281 (1.9%)
-0.02
35 (0.1%)
28 (0.2%)
-0.03
N/A
N/A
#VALUE!
436 (0.8%)
309 (0.9%)
-0.01
Lab values- BNP (within 3 months); n (%)
281 (1.1%)
224 (1.5%)
-0.04
28 (0.1%)
18 (0.1%)
0.00
N/A
N/A
#VALUE!
309 (0.5%)
242 (0.7%)
-0.03
Lab values- BNP (within 6 months); n (%)
401 (1.6%)
281 (1.9%)
-0.02
35 (0.1%)
28 (0.2%)
-0.03
N/A
N/A
#VALUE!
436 (0.8%)
309 (0.9%)
-0.01
Lab values- BUN (mg/dl); n (%)
6,014 (23.4%)
4,675 (31.4%)
-0.18
409 (1.3%)
390 (2.2%)
-0.07
N/A
N/A
#VALUE!
6,423 (11.1%)
5,065 (15.5%)
-0.13
Lab values- BUN (mg/dl) (within 3 months); n (%)
4,107 (16.0%)
3,320 (22.3%)
-0.16
282 (0.9%)
290 (1.6%)
-0.06
N/A
N/A
#VALUE!
4,389 (7.6%)
3,610 (11.1%)
-0.12
Lab values- BUN (mg/dl) (within 6 months); n (%)
6,014 (23.4%)
4,675 (31.4%)
-0.18
409 (1.3%)
390 (2.2%)
-0.07
N/A
N/A
#VALUE!
6,423 (11.1%)
5,065 (15.5%)
-0.13
Lab values- Creatinine (mg/dl) v2; n (%)
6,112 (23.8%)
4,840 (32.6%)
-0.20
423 (1.3%)
412 (2.3%)
-0.08
N/A
N/A
#VALUE!
6,535 (11.3%)
5,252 (16.1%)
-0.14
Lab values- Creatinine (mg/dl) (within 3 months) v2; 
n (%)
4,168 (16.2%)
3,454 (23.2%)
-0.18
293 (0.9%)
308 (1.7%)
-0.07
N/A
N/A
#VALUE!
4,461 (7.7%)
3,762 (11.5%)
-0.13
Lab values- Creatinine (mg/dl) (within 6 months) v2; 
n (%)
6,112 (23.8%)
4,840 (32.6%)
-0.20
423 (1.3%)
412 (2.3%)
-0.08
N/A
N/A
#VALUE!
6,535 (11.3%)
5,252 (16.1%)
-0.14
Lab values- HDL level (mg/dl); n (%)
4,306 (16.8%)
3,409 (22.9%)
-0.15
373 (1.2%)
270 (1.5%)
-0.03
N/A
N/A
#VALUE!
4,679 (8.1%)
3,679 (11.3%)
-0.11
Lab values- HDL level (mg/dl) (within 3 months); n (%)
2,689 (10.5%)
2,126 (14.3%)
-0.12
251 (0.8%)
181 (1.0%)
-0.02
N/A
N/A
#VALUE!
2,940 (5.1%)
2,307 (7.1%)
-0.08
Lab values- HDL level (mg/dl) (within 6 months); n (%)
4,306 (16.8%)
3,409 (22.9%)
-0.15
373 (1.2%)
270 (1.5%)
-0.03
N/A
N/A
#VALUE!
4,679 (8.1%)
3,679 (11.3%)
-0.11
Lab values- LDL level (mg/dl) v2; n (%)
4,523 (17.6%)
3,538 (23.8%)
-0.15
452 (1.4%)
279 (1.6%)
-0.02
N/A
N/A
#VALUE!
4,975 (8.6%)
3,817 (11.7%)
-0.10
Lab values- LDL level (mg/dl) (within 3 months) v2; n 
(%)
2,835 (11.0%)
2,212 (14.9%)
-0.12
296 (0.9%)
185 (1.0%)
-0.01
N/A
N/A
#VALUE!
3,131 (5.4%)
2,397 (7.3%)
-0.08
Lab values- LDL level (mg/dl) (within 6 months) v2; n 
(%)
4,523 (17.6%)
3,538 (23.8%)
-0.15
452 (1.4%)
279 (1.6%)
-0.02
N/A
N/A
#VALUE!
4,975 (8.6%)
3,817 (11.7%)
-0.10
Lab values- NT-proBNP; n (%)
48 (0.2%)
41 (0.3%)
-0.02
5 (0.0%)
4 (0.0%)
#DIV/0!
N/A
N/A
#VALUE!
53 (0.1%)
45 (0.1%)
0.00
Lab values- NT-proBNP (within 3 months); n (%)
37 (0.1%)
34 (0.2%)
-0.03
2 (0.0%)
3 (0.0%)
#DIV/0!
N/A
N/A
#VALUE!
39 (0.1%)
37 (0.1%)
-
Lab values- NT-proBNP (within 6 months); n (%)
48 (0.2%)
41 (0.3%)
-0.02
5 (0.0%)
4 (0.0%)
#DIV/0!
N/A
N/A
#VALUE!
53 (0.1%)
45 (0.1%)
-
Lab values- Total cholesterol (mg/dl) v2; n (%)
4,382 (17.0%)
3,446 (23.2%)
-0.16
372 (1.2%)
269 (1.5%)
-0.03
N/A
N/A
#VALUE!
4,754 (8.2%)
3,715 (11.4%)
-0.11
Lab values- Total cholesterol (mg/dl) (within 3 
months) v2; n (%)
2,738 (10.7%)
2,151 (14.5%)
-0.11
246 (0.8%)
180 (1.0%)
-0.02
N/A
N/A
#VALUE!
2,984 (5.1%)
2,331 (7.1%)
-0.08
Appendix B: Rivaroxaban vs Warfarin

Lab values- Total cholesterol (mg/dl) (within 6 
months) v2; n (%)
4,382 (17.0%)
3,446 (23.2%)
-0.16
372 (1.2%)
269 (1.5%)
-0.03
N/A
N/A
#VALUE!
4,754 (8.2%)
3,715 (11.4%)
-0.11
Lab values- Triglyceride level (mg/dl); n (%)
4,300 (16.7%)
3,427 (23.0%)
-0.16
358 (1.1%)
271 (1.5%)
-0.04
N/A
N/A
#VALUE!
4,658 (8.0%)
3,698 (11.3%)
-0.11
Lab values- Triglyceride level (mg/dl) (within 3 
months); n (%)
2,685 (10.4%)
2,139 (14.4%)
-0.12
240 (0.7%)
182 (1.0%)
-0.03
N/A
N/A
#VALUE!
2,925 (5.0%)
2,321 (7.1%)
-0.09
Lab values- Triglyceride level (mg/dl) (within 6 
months); n (%)
4,300 (16.7%)
3,427 (23.0%)
-0.16
358 (1.1%)
271 (1.5%)
-0.04
N/A
N/A
#VALUE!
4,658 (8.0%)
3,698 (11.3%)
-0.11
Lab result number- HbA1c (%) mean (only 2 to 20 
included) v4
3,412
                                            
2,685
                                            
365
                                                
233
                                                
N/A
N/A
                                             3,777                                              2,918 
...mean (sd)
6.57 (1.15)
6.43 (1.14)
0.12
6.95 (1.39)
6.74 (1.22)
0.16
N/A
N/A
#VALUE!
6.61 (1.18)
6.45 (1.15)
0.14
...median [IQR]
6.30 [5.90, 7.00]
6.20 [5.70, 6.80]
0.09
6.55 [6.05, 7.50]
6.50 [6.00, 7.20]
0.04
N/A
N/A
#VALUE!
6.32 (1.18)
6.22 (1.15)
0.09
...Missing; n (%)
22,289 (86.7%)
12,184 (81.9%)
0.13
31,930 (98.9%)
17,515 (98.7%)
0.02
N/A
N/A
#VALUE!
54,219 (93.5%)
29,699 (91.1%)
0.09
Lab result number- BNP mean v2
401
                                                
281
                                                
35
                                                   
28
                                                   
N/A
N/A
                                                 436                                                  309 
...mean (sd)
321.38 (381.79)
308.78 (481.63)
0.03
534.56 (854.48)
412.18 (586.24)
0.17
N/A
N/A
#VALUE!
338.49 (438.16)
318.15 (492.53)
0.04
...median [IQR]
217.00 [123.80, 376.80]
197.00 [93.20, 325.50]
0.05
187.50 [119.00, 531.25]
148.90 [93.00, 375.75]
0.05
N/A
N/A
#VALUE!
214.63 (438.16)
192.64 (492.53)
0.05
...Missing; n (%)
25,300 (98.4%)
14,588 (98.1%)
0.02
32,260 (99.9%)
17,720 (99.8%)
0.03
N/A
N/A
#VALUE!
57,560 (99.2%)
32,308 (99.1%)
0.01
Lab result number- BUN (mg/dl) mean v2
                                             6,014                                              4,675 
                                                 409                                                  390 
N/A
N/A
                                             6,423                                              5,065 
...mean (sd)
18.98 (7.10)
17.84 (5.88)
0.17
19.26 (8.32)
1,005.73 (11,839.99)
-0.12
N/A
N/A
#VALUE!
19.00 (7.18)
93.91 (3282.21)
-0.03
...median [IQR]
18.00 [14.33, 22.00]
17.00 [14.00, 21.00]
0.15
18.00 [15.00, 22.00]
17.90 [15.00, 22.50]
0.00
N/A
N/A
#VALUE!
18.00 (7.18)
#VALUE!
#VALUE!
...Missing; n (%)
19,687 (76.6%)
10,194 (68.6%)
0.18
31,886 (98.7%)
17,358 (97.8%)
0.07
N/A
N/A
#VALUE!
51,573 (88.9%)
27,552 (84.5%)
0.13
Lab result number- Creatinine (mg/dl) mean (only 0.1 
to 15 included) v3
                                             6,060                                              4,790 
                                                 413                                                  403 
N/A
N/A
                                             6,473                                              5,193 
...mean (sd)
1.00 (0.26)
0.95 (0.23)
0.20
1.03 (0.29)
0.97 (0.23)
0.23
N/A
N/A
#VALUE!
1.00 (0.26)
0.95 (0.23)
0.20
...median [IQR]
0.96 [0.82, 1.12]
0.93 [0.80, 1.07]
0.12
0.99 [0.84, 1.17]
0.96 [0.81, 1.10]
0.11
N/A
N/A
#VALUE!
0.96 (0.26)
0.93 (0.23)
0.12
...Missing; n (%)
19,641 (76.4%)
10,079 (67.8%)
0.19
31,882 (98.7%)
17,345 (97.7%)
0.08
N/A
N/A
#VALUE!
51,523 (88.8%)
27,424 (84.1%)
0.14
Lab result number- HDL level (mg/dl) mean (only 
=<5000 included) v2
                                             4,306                                              3,409 
                                                 373                                                  269 
N/A
N/A
                                             4,679                                              3,678 
...mean (sd)
51.05 (16.15)
52.83 (16.13)
-0.11
44.36 (16.11)
46.29 (16.99)
-0.12
N/A
N/A
#VALUE!
50.52 (16.15)
52.35 (16.20)
-0.11
...median [IQR]
48.50 [40.00, 60.00]
50.00 [41.67, 62.00]
-0.09
44.00 [34.75, 52.00]
45.00 [37.00, 55.00]
-0.06
N/A
N/A
#VALUE!
48.14 (16.15)
49.63 (16.20)
-0.09
...Missing; n (%)
21,395 (83.2%)
11,460 (77.1%)
0.15
31,922 (98.8%)
17,479 (98.5%)
0.03
N/A
N/A
#VALUE!
53,317 (91.9%)
28,939 (88.7%)
0.11
Lab result number- LDL level (mg/dl) mean (only 
=<5000 included) v2
                                             4,420                                              3,473 
                                                 367                                                  269 
N/A
N/A
                                             4,787                                              3,742 
...mean (sd)
85.74 (33.20)
87.86 (33.40)
-0.06
81.43 (33.48)
87.95 (39.03)
-0.18
N/A
N/A
#VALUE!
85.41 (33.22)
87.87 (33.84)
-0.07
...median [IQR]
81.00 [64.00, 104.00]
84.00 [64.00, 106.00]
-0.09
79.00 [62.00, 101.00]
86.00 [64.00, 110.25]
-0.19
N/A
N/A
#VALUE!
80.85 (33.22)
84.14 (33.84)
-0.10
...Missing; n (%)
21,281 (82.8%)
11,396 (76.6%)
0.15
31,928 (98.9%)
17,479 (98.5%)
0.04
N/A
N/A
#VALUE!
53,209 (91.7%)
28,875 (88.5%)
0.11
Lab result number- Total cholesterol (mg/dl) mean 
(only =<5000 included) v2
                                             4,379                                              3,443 
                                                 372                                                  267 
N/A
N/A
                                             4,751                                              3,710 
...mean (sd)
162.98 (40.62)
166.15 (40.57)
-0.08
153.52 (43.84)
161.18 (52.03)
-0.16
N/A
N/A
#VALUE!
162.24 (40.88)
165.79 (41.50)
-0.09
...median [IQR]
158.50 [135.50, 186.00]
162.00 [138.00, 189.00]
-0.09
154.00 [133.00, 176.00]
159.00 [131.00, 191.00]
-0.10
N/A
N/A
#VALUE!
158.15 (40.88)
161.78 (41.50)
-0.09
...Missing; n (%)
21,322 (83.0%)
11,426 (76.8%)
0.16
31,923 (98.8%)
17,481 (98.5%)
0.03
N/A
N/A
#VALUE!
53,245 (91.8%)
28,907 (88.6%)
0.11
Lab result number- Triglyceride level (mg/dl) mean 
(only =<5000 included) v2
                                             4,300                                              3,427 
                                                 358                                                  270 
N/A
N/A
                                             4,658                                              3,697 
...mean (sd)
130.55 (80.73)
125.44 (72.65)
0.07
143.25 (85.57)
128.35 (78.86)
0.18
N/A
N/A
#VALUE!
131.53 (81.12)
125.65 (73.13)
0.08
...median [IQR]
113.00 [82.00, 154.00]
107.00 [80.00, 152.00]
0.08
126.00 [88.00, 179.00]
117.50 [79.75, 157.50]
0.10
N/A
N/A
#VALUE!
114.00 (81.12)
107.77 (73.13)
0.08
...Missing; n (%)
21,401 (83.3%)
11,442 (77.0%)
0.16
31,937 (98.9%)
17,478 (98.5%)
0.04
N/A
N/A
#VALUE!
53,338 (92.0%)
28,920 (88.7%)
0.11
Lab result number- Hemoglobin mean (only >0 
included)
                                             4,383                                              3,561 
                                                 284                                                  285 
N/A
N/A
                                             4,667                                              3,846 
...mean (sd)
13.66 (1.55)
13.78 (1.61)
-0.08
13.12 (2.32)
815.42 (10,013.02)
-0.11
N/A
N/A
#VALUE!
13.63 (1.61)
73.18 (2722.01)
-0.03
...median [IQR]
13.60 [12.70, 14.70]
13.80 [12.76, 14.82]
-0.13
13.40 [12.30, 14.47]
14.00 [12.80, 14.90]
0.00
N/A
N/A
#VALUE!
13.59 (1.61)
#VALUE!
#VALUE!
...Missing; n (%)
21,318 (82.9%)
11,308 (76.1%)
0.17
32,011 (99.1%)
17,463 (98.4%)
0.06
N/A
N/A
#VALUE!
53,329 (92.0%)
28,771 (88.2%)
0.13
Lab result number- Serum sodium mean (only > 90 
and < 190 included)
                                             5,895                                              4,582 
                                                 341                                                  365 
N/A
N/A
                                             6,236                                              4,947 
...mean (sd)
140.05 (2.96)
140.27 (2.94)
-0.07
139.62 (3.02)
139.71 (2.77)
-0.03
N/A
N/A
#VALUE!
140.03 (2.96)
140.23 (2.93)
-0.07
...median [IQR]
140.00 [138.50, 142.00]
140.50 [139.00, 142.00]
-0.17
140.00 [138.00, 141.00]
140.00 [138.00, 142.00]
0.00
N/A
N/A
#VALUE!
140.00 (2.96)
140.46 (2.93)
-0.16
...Missing; n (%)
19,806 (77.1%)
10,287 (69.2%)
0.18
31,954 (98.9%)
17,383 (97.9%)
0.08
N/A
N/A
#VALUE!
51,760 (89.2%)
27,670 (84.8%)
0.13
Lab result number- Albumin mean (only >0 and <=10 
included)
                                             5,206                                              4,061 
                                                 263                                                  286 
N/A
N/A
                                             5,469                                              4,347 
...mean (sd)
4.14 (0.32)
4.19 (0.33)
-0.15
4.01 (0.70)
4.09 (0.59)
-0.12
N/A
N/A
#VALUE!
4.13 (0.35)
4.18 (0.35)
-0.14
...median [IQR]
4.15 [3.95, 4.35]
4.20 [4.00, 4.40]
-0.15
4.10 [3.83, 4.35]
4.20 [4.00, 4.40]
-0.15
N/A
N/A
#VALUE!
4.15 (0.35)
4.20 (0.35)
-0.14
...Missing; n (%)
20,495 (79.7%)
10,808 (72.7%)
0.16
32,032 (99.2%)
17,462 (98.4%)
0.07
N/A
N/A
#VALUE!
52,527 (90.6%)
28,270 (86.7%)
0.12
Lab result number- Glucose (fasting or random) mean 
(only 10-1000 included)
                                             5,816                                              4,563 
                                                 336                                                  362 
N/A
N/A
                                             6,152                                              4,925 
...mean (sd)
113.88 (37.92)
112.94 (36.12)
0.03
128.18 (55.83)
129.74 (45.68)
-0.03
N/A
N/A
#VALUE!
114.66 (39.11)
114.17 (36.91)
0.01
...median [IQR]
103.00 [92.00, 122.00]
103.00 [93.00, 121.00]
0.00
114.00 [97.00, 138.94]
117.00 [100.00, 143.08]
-0.06
N/A
N/A
#VALUE!
103.60 (39.11)
104.03 (36.91)
-0.01
...Missing; n (%)
19,885 (77.4%)
10,306 (69.3%)
0.18
31,959 (99.0%)
17,386 (98.0%)
0.08
N/A
N/A
#VALUE!
51,844 (89.4%)
27,692 (84.9%)
0.13
Lab result number- Potassium mean (only 1-7 
included)
                                             6,075                                              4,778 
                                                 402                                                  377 
N/A
N/A
                                             6,477                                              5,155 
Appendix B: Rivaroxaban vs Warfarin

...mean (sd)
4.35 (0.44)
4.38 (0.44)
-0.07
4.33 (0.42)
4.34 (0.41)
-0.02
N/A
N/A
#VALUE!
4.35 (0.44)
4.38 (0.44)
-0.07
...median [IQR]
4.30 [4.10, 4.60]
4.40 [4.10, 4.65]
-0.23
4.30 [4.10, 4.60]
4.30 [4.10, 4.60]
0.00
N/A
N/A
#VALUE!
4.30 (0.44)
4.39 (0.44)
-0.20
...Missing; n (%)
19,626 (76.4%)
10,091 (67.9%)
0.19
31,893 (98.8%)
17,371 (97.9%)
0.07
N/A
N/A
#VALUE!
51,519 (88.8%)
27,462 (84.2%)
0.13
Comorbidity Scores
CCI (180 days)- ICD9 and ICD10 v2
...mean (sd)
3.37 (1.73)
3.44 (1.71)
-0.04
3.01 (1.67)
3.08 (1.56)
-0.04
2.87 (2.10)
2.90 (2.09)
-0.01
2.99 (1.95)
3.05 (1.90)
-0.03
...median [IQR]
3.00 [2.00, 4.00]
3.00 [2.00, 5.00]
0.00
3.00 [2.00, 4.00]
3.00 [2.00, 4.00]
0.00
3.00 [1.00, 4.00]
3.00 [1.00, 4.00]
0.00
3.00 (1.95)
3.00 (1.90)
0.00
Non-Frailty; n (%)
13,921 (54.2%)
8,405 (56.5%)
-0.05
16,295 (50.5%)
9,068 (51.1%)
-0.01
2,130 (2.3%)
887 (2.2%)
0.01
32,346 (21.5%)
18,360 (25.1%)
-0.09
Frailty Score (mean): Empirical Version 365 days, v2
...mean (sd)
0.19 (0.06)
0.19 (0.06)
0.00
0.19 (0.05)
0.18 (0.05)
0.20
18.75 (12.79)
17.17 (12.78)
0.12
11.59 (10.03)
9.61 (9.52)
0.20
...median [IQR]
0.18 [0.15, 0.22]
0.18 [0.15, 0.21]
0.00
0.18 [0.15, 0.21]
0.17 [0.15, 0.20]
0.20
16.16 [9.68, 25.10]14.51 [8.15, 23.26]
0.13
10.00 (10.03)
8.13 (9.52)
0.19
Healthcare Utilization
Any hospitalization; n (%)
5,289 (20.6%)
3,814 (25.7%)
-0.12
7,942 (24.6%)
5,601 (31.6%)
-0.16
35,792 (38.7%)
20,776 (51.1%)
-0.25
49,023 (32.6%)
30,191 (41.2%)
-0.18
Any hospitalization within prior 30 days; n (%)
3,558 (13.8%)
2,423 (16.3%)
-0.07
4,737 (14.7%)
3,876 (21.8%)
-0.18
21,828 (23.6%)
13,998 (34.4%)
-0.24
30123 (20.0%)
20297 (27.7%)
-0.18
Any hospitalization during prior 31-180 days; n (%)
2,003 (7.8%)
1,604 (10.8%)
-0.10
3,530 (10.9%)
1,982 (11.2%)
-0.01
16,767 (18.1%)
8,551 (21.0%)
-0.07
22300 (14.8%)
12137 (16.6%)
-0.05
Endocrinologist Visit; n (%)
745 (2.9%)
496 (3.3%)
-0.02
1,051 (3.3%)
737 (4.2%)
-0.05
4,770 (5.2%)
2,301 (5.7%)
-0.02
6566 (4.4%)
3534 (4.8%)
-0.02
Endocrinologist Visit (30 days prior); n (%)
254 (1.0%)
165 (1.1%)
-0.01
343 (1.1%)
253 (1.4%)
-0.03
1,441 (1.6%)
779 (1.9%)
-0.02
2038 (1.4%)
1197 (1.6%)
-0.02
Endocrinologist Visit (31 to 180 days prior); n (%)
614 (2.4%)
412 (2.8%)
-0.03
903 (2.8%)
621 (3.5%)
-0.04
4,153 (4.5%)
1,951 (4.8%)
-0.01
5670 (3.8%)
2984 (4.1%)
-0.02
Internal medicine/family medicine visits; n (%)
22,697 (88.3%)
12,893 (86.7%)
0.05
25,755 (79.7%)
14,625 (82.4%)
-0.07
79,393 (85.9%)
36,147 (88.9%)
-0.09
127845 (85.0%)
63665 (86.9%)
-0.05
Internal medicine/family medicine visits (30 days 
prior) v2; n (%)
16,026 (62.4%)
8,775 (59.0%)
0.07
16,896 (52.3%)
10,186 (57.4%)
-0.10
53,989 (58.4%)
26,439 (65.0%)
-0.14
86911 (57.8%)
45400 (62.0%)
-0.09
Internal medicine/family medicine visits (31 to 180 
days prior) v2; n (%)
20,181 (78.5%)
11,309 (76.1%)
0.06
23,468 (72.7%)
12,754 (71.9%)
0.02
70,359 (76.1%)
31,172 (76.7%)
-0.01
114008 (75.8%)
55235 (75.4%)
0.01
Cardiologist visit; n (%)
17,320 (67.4%)
12,047 (81.0%)
-0.31
17,116 (53.0%)
11,195 (63.1%)
-0.21
71,688 (77.6%)
35,047 (86.2%)
-0.22
106124 (70.6%)
58289 (79.6%)
-0.21
Number of Cardiologist visits (30 days prior); n (%)
12,102 (47.1%)
9,678 (65.1%)
-0.37
10,270 (31.8%)
9,109 (51.3%)
-0.40
46,370 (50.2%)
27,902 (68.6%)
-0.38
68742 (45.7%)
46689 (63.7%)
-0.37
Number of Cardiologist visits (31 to 180 days prior); 
n (%)
11,899 (46.3%)
7,468 (50.2%)
-0.08
13,333 (41.3%)
6,899 (38.9%)
0.05
52,530 (56.8%)
21,981 (54.1%)
0.05
77762 (51.7%)
36348 (49.6%)
0.04
Electrocardiogram v2; n (%)
16,445 (64.0%)
12,125 (81.5%)
-0.40
19,397 (60.1%)
14,074 (79.3%)
-0.43
66,036 (71.5%)
35,363 (87.0%)
-0.39
101878 (67.7%)
61562 (84.0%)
-0.39
Use of glucose test strips; n (%)
348 (1.4%)
227 (1.5%)
-0.01
334 (1.0%)
217 (1.2%)
-0.02
1,863 (2.0%)
1,006 (2.5%)
-0.03
2545 (1.7%)
1450 (2.0%)
-0.02
Dialysis; n (%)
3 (0.0%)
0 (0.0%)
#DIV/0!
0 (0.0%)
0 (0.0%)
#DIV/0!
**
**
#VALUE!
#VALUE!
#VALUE!
#VALUE!
number of different/distinct medication 
prescriptions
...mean (sd)
8.98 (4.25)
9.52 (4.58)
-0.12
9.50 (4.46)
9.73 (4.60)
-0.05
10.36 (4.52)
11.16 (4.98)
-0.17
9.94 (4.46)
10.48 (4.81)
0.00
...median [IQR]
8.00 [6.00, 11.00]
9.00 [6.00, 12.00]
-0.23
9.00 [6.00, 12.00]
9.00 [6.00, 12.00]
0.00
10.00 [7.00, 13.00]10.00 [8.00, 14.00]
0.00
5.45 (5.28)
6.43 (5.46)
0.00
Number of Hospitalizations
...mean (sd)
0.23 (0.50)
0.29 (0.55)
-0.11
0.27 (0.50)
0.35 (0.54)
-0.15
0.49 (0.72)
0.64 (0.76)
-0.20
0.40 (0.64)
0.50 (0.67)
0.00
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 1.00]
0.00
0.00 [0.00, 0.00]
0.00 [0.00, 1.00]
0.00
0.00 [0.00, 1.00]
1.00 [0.00, 1.00]
-1.35
0.00 (0.72)
0.24 (0.74)
0.00
Number of hospital days
...mean (sd)
1.17 (3.39)
1.27 (3.31)
-0.03
1.47 (4.58)
1.48 (3.36)
0.00
2.99 (6.48)
3.45 (6.68)
-0.07
2.35 (5.68)
2.53 (5.45)
0.00
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 1.00]
0.00
0.00 [0.00, 0.00]
0.00 [0.00, 2.00]
0.00
0.00 [0.00, 4.00]
2.00 [0.00, 5.00]
-0.30
0.00 (6.38)
0.48 (5.77)
0.00
Number of Emergency Department (ED) visits v3
...mean (sd)
0.60 (1.20)
0.81 (1.47)
-0.16
0.43 (1.72)
0.69 (2.35)
-0.13
1.08 (1.75)
1.38 (1.98)
-0.16
0.86 (1.66)
1.10 (1.99)
0.00
...median [IQR]
0.00 [0.00, 1.00]
0.00 [0.00, 1.00]
0.00
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 [0.00, 2.00]
1.00 [0.00, 2.00]
-0.54
0.00 (1.99)
0.24 (2.38)
0.00
Number of Office visits
...mean (sd)
5.56 (4.39)
5.73 (3.98)
-0.04
6.45 (5.08)
5.89 (4.11)
0.12
13.98 (13.90)
13.94 (13.20)
0.00
10.92 (11.29)
10.32 (10.20)
0.00
...median [IQR]
5.00 [2.00, 8.00]
5.00 [3.00, 8.00]
0.00
5.00 [3.00, 9.00]
5.00 [3.00, 8.00]
0.00
10.00 [5.00, 19.00]11.00 [5.00, 18.00]
-0.07
4.08 (11.74)
4.89 (10.45)
0.00
Number of Endocrinologist visits
...mean (sd)
0.11 (1.11)
0.13 (1.11)
-0.02
0.12 (1.01)
0.16 (1.25)
-0.04
0.26 (1.93)
0.27 (1.84)
-0.01
0.20 (1.65)
0.21 (1.58)
0.00
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 (1.77)
0.00 (1.73)
0.00
Number of internal medicine/family medicine visits
...mean (sd)
10.42 (12.51)
9.05 (11.93)
0.11
8.01 (11.59)
7.29 (10.23)
0.07
9.70 (11.61)
9.63 (10.82)
0.01
9.46 (11.76)
8.95 (10.92)
0.00
...median [IQR]
7.00 [2.00, 14.00]
6.00 [2.00, 12.00]
0.08
4.00 [1.00, 10.00]
4.00 [1.00, 9.00]
0.00
6.00 [2.00, 13.00] 7.00 [3.00, 13.00]
-0.09
3.34 (13.86)
3.88 (12.32)
0.00
Number of Cardiologist visits
...mean (sd)
4.23 (5.80)
5.24 (5.92)
-0.17
3.14 (5.45)
3.46 (4.82)
-0.06
5.69 (7.71)
6.37 (7.97)
-0.09
4.89 (6.97)
5.44 (6.93)
0.00
...median [IQR]
2.00 [0.00, 6.00]
4.00 [1.00, 7.00]
-0.34
1.00 [0.00, 4.00]
2.00 [0.00, 5.00]
-0.19
3.00 [1.00, 8.00]
4.00 [2.00, 9.00]
-0.13
1.20 (7.78)
2.27 (7.43)
0.00
Number electrocardiograms received v2
...mean (sd)
1.62 (2.18)
2.42 (2.58)
-0.33
1.36 (1.88)
1.99 (2.05)
-0.32
2.05 (2.35)
2.85 (2.57)
-0.32
1.83 (2.23)
2.55 (2.46)
0.00
...median [IQR]
1.00 [0.00, 2.00]
2.00 [1.00, 3.00]
-0.42
1.00 [0.00, 2.00]
1.00 [1.00, 3.00]
0.00
1.00 [0.00, 3.00]
2.00 [1.00, 4.00]
-0.41
0.60 (2.53)
1.13 (2.71)
0.00
Number of HbA1c tests ordered
...mean (sd)
0.46 (0.73)
0.49 (0.73)
-0.04
0.21 (0.54)
0.27 (0.59)
-0.11
0.57 (0.81)
0.59 (0.82)
-0.02
0.47 (0.75)
0.49 (0.75)
0.00
...median [IQR]
0.00 [0.00, 1.00]
0.00 [0.00, 1.00]
0.00
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 [0.00, 1.00]
0.00 [0.00, 1.00]
0.00
0.00 (0.82)
0.00 (0.82)
0.00
Number of glucose tests ordered
...mean (sd)
0.19 (1.94)
0.20 (0.86)
-0.01
0.13 (0.81)
0.15 (0.84)
-0.02
0.20 (0.94)
0.23 (0.75)
-0.04
0.18 (1.15)
0.20 (0.80)
0.00
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 (1.26)
0.00 (0.92)
0.00
Number of lipid tests ordered
...mean (sd)
0.63 (0.82)
0.71 (0.84)
-0.10
0.27 (0.68)
0.40 (0.88)
-0.17
0.66 (0.77)
0.72 (0.80)
-0.08
0.57 (0.76)
0.64 (0.83)
0.00
Appendix B: Rivaroxaban vs Warfarin

...median [IQR]
0.00 [0.00, 1.00]
1.00 [0.00, 1.00]
-1.20
0.00 [0.00, 0.00]
0.00 [0.00, 1.00]
0.00
1.00 [0.00, 1.00]
1.00 [0.00, 1.00]
0.00
0.21 (0.87)
0.45 (0.96)
0.00
Number of creatinine tests ordered
...mean (sd)
0.07 (0.39)
0.07 (0.34)
0.00
0.06 (0.36)
0.05 (0.29)
0.03
0.12 (0.49)
0.11 (0.43)
0.02
0.10 (0.45)
0.09 (0.38)
0.00
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 (0.50)
0.00 (0.42)
0.00
Number of BUN tests ordered
...mean (sd)
0.04 (0.32)
0.04 (0.26)
0.00
0.04 (0.27)
0.03 (0.23)
0.04
0.08 (0.40)
0.07 (0.33)
0.03
0.06 (0.36)
0.05 (0.29)
0.00
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 (0.40)
0.00 (0.32)
0.00
Number of tests for microalbuminuria
...mean (sd)
0.22 (0.66)
0.22 (0.66)
0.00
0.09 (0.42)
0.11 (0.47)
-0.04
0.16 (0.48)
0.17 (0.49)
-0.02
0.16 (0.50)
0.17 (0.52)
0.00
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 (0.57)
0.00 (0.59)
0.00
Total N distinct ICD9/ICD10 diagnoses at the 3rd 
digit level Copy
...mean (sd)
5.69 (7.91)
8.77 (9.30)
-0.36
2.78 (5.59)
4.42 (6.78)
-0.26
9.07 (11.13)
11.98 (12.28)
-0.25
7.14 (9.67)
9.50 (10.60)
0.00
...median [IQR]
3.00 [0.00, 9.00]
7.00 [0.00, 13.00]
-0.46
0.00 [0.00, 3.00]
1.00 [0.00, 7.00]
-0.16
5.00 [0.00, 15.00] 9.00 [0.00, 19.00]
-0.34
1.59 (10.30)
3.84 (11.26)
0.00
For PS
Hemorrhagic stroke+Other cerebrovascular 
disease+Cerebrovascular procedure (for PS); n (%)
912 (3.5%)
691 (4.6%)
-0.06
986 (3.1%)
607 (3.4%)
-0.02
4,474 (4.8%)
2,233 (5.5%)
-0.03
6372 (4.2%)
3531 (4.8%)
-0.03
Occurrence of creatinine tests ordered (for PS); n (%)
1,338 (5.2%)
824 (5.5%)
-0.01
1,445 (4.5%)
732 (4.1%)
0.02
8,254 (8.9%)
3,521 (8.7%)
0.01
11037 (7.3%)
5077 (6.9%)
0.02
Occurrence of BUN tests ordered (for PS); n (%)
824 (3.2%)
492 (3.3%)
-0.01
873 (2.7%)
479 (2.7%)
0.00
5,372 (5.8%)
2,228 (5.5%)
0.01
7069 (4.7%)
3199 (4.4%)
0.01
Occurrence of chronic renal insufficiency w/o CKD 
(for PS) v2; n (%)
0 (0.0%)
0 (0.0%)
#DIV/0!
0 (0.0%)
0 (0.0%)
#DIV/0!
682 (0.7%)
243 (0.6%)
0.01
682 (0.5%)
243 (0.3%)
0.03
Chronic kidney disease Stage 1-2 (for PS); n (%)
0 (0.0%)
0 (0.0%)
#DIV/0!
0 (0.0%)
0 (0.0%)
#DIV/0!
0
0
#VALUE!
#VALUE!
#VALUE!
#VALUE!
Chronic kidney disease Stage 3-6 (for PS); n (%)
0 (0.0%)
0 (0.0%)
#DIV/0!
0 (0.0%)
0 (0.0%)
#DIV/0!
1,912 (2.1%)
547 (1.3%)
0.06
1912 (1.3%)
547 (0.7%)
0.06
Bladder stones+Kidney stones (for PS); n (%)
210 (0.8%)
179 (1.2%)
-0.04
313 (1.0%)
209 (1.2%)
-0.02
1,291 (1.4%)
685 (1.7%)
-0.02
1814 (1.2%)
1073 (1.5%)
-0.03
Diabetes with peripheral circulatory 
disorders+Gangrene+Osteomyelitis(for PS) v3 with 
ICD10 Copy; n (%)
943 (3.7%)
452 (3.0%)
0.04
939 (2.9%)
397 (2.2%)
0.04
5,228 (5.7%)
2,132 (5.2%)
0.02
7110 (4.7%)
2981 (4.1%)
0.03
Alcohol abuse or dependence+Drug abuse or 
dependence (for PS); n (%)
0 (0.0%)
0 (0.0%)
#DIV/0!
0 (0.0%)
0 (0.0%)
#DIV/0!
173 (0.2%)
139 (0.3%)
-0.02
173 (0.1%)
139 (0.2%)
-0.03
Diabetes with other ophthalmic 
manifestations+Retinal detachment, vitreous 
hemorrhage, vitrectomy+Retinal laser coagulation 
therapy (for PS); n (%)
115 (0.4%)
84 (0.6%)
-0.03
555 (1.7%)
220 (1.2%)
0.04
1,437 (1.6%)
593 (1.5%)
0.01
2107 (1.4%)
897 (1.2%)
0.02
Other atherosclerosis+Cardiac conduction 
disorders+Other CVD (for PS) v2 Copy; n (%)
10,167 (39.6%)
6,504 (43.7%)
-0.08
11,709 (36.3%)
6,953 (39.2%)
-0.06
37,639 (40.7%)
18,343 (45.1%)
-0.09
59515 (39.6%)
31800 (43.4%)
-0.08
Previous cardiac procedure (CABG or PTCA or Stent) + 
History of CABG or PTCA (for PS) v3; n (%)
2,140 (8.3%)
1,535 (10.3%)
-0.07
1,558 (4.8%)
947 (5.3%)
-0.02
12,496 (13.5%)
6,545 (16.1%)
-0.07
16194 (10.8%)
9027 (12.3%)
-0.05
Hyperthyroidism + Hypothyroidism + Other disorders 
of thyroid gland (for PS); n (%)
5,181 (20.2%)
3,309 (22.3%)
-0.05
4,641 (14.4%)
3,058 (17.2%)
-0.08
16,724 (18.1%)
6,901 (17.0%)
0.03
26546 (17.7%)
13268 (18.1%)
-0.01
Delirium + Psychosis (for PS); n (%)
679 (2.6%)
400 (2.7%)
-0.01
861 (2.7%)
369 (2.1%)
0.04
4,298 (4.7%)
2,093 (5.1%)
-0.02
5838 (3.9%)
2862 (3.9%)
0.00
Any use of Meglitinides (for PS); n (%)
56 (0.2%)
43 (0.3%)
-0.02
166 (0.5%)
80 (0.5%)
0.00
460 (0.5%)
200 (0.5%)
0.00
682 (0.5%)
323 (0.4%)
0.01
Any use of AGIs (for PS); n (%)
24 (0.1%)
10 (0.1%)
0.00
46 (0.1%)
12 (0.1%)
0.00
139 (0.2%)
57 (0.1%)
0.03
209 (0.1%)
79 (0.1%)
0.00
CKD stage 3-6 + dialysis (for PS); n (%)
3 (0.0%)
1 (0.0%)
#DIV/0!
1 (0.0%)
0 (0.0%)
#DIV/0!
1,917 (2.1%)
549 (1.4%)
0.05
1921 (1.3%)
550 (0.8%)
0.05
Use of thiazide- United; n (%)
3,246 (12.6%)
1,792 (12.1%)
0.02
3,732 (11.6%)
2,078 (11.7%)
0.00
11,852 (12.8%)
5,583 (13.7%)
-0.03
18830 (12.5%)
9453 (12.9%)
-0.01
Use of beta blockers; n (%)
17,651 (68.7%)
10,352 (69.6%)
-0.02
22,255 (68.9%)
12,673 (71.4%)
-0.05
67,017 (72.5%)
30,360 (74.7%)
-0.05
106923 (71.1%)
53385 (72.9%)
-0.04
Use of calcium channel blockers; n (%)
9,670 (37.6%)
6,047 (40.7%)
-0.06
12,176 (37.7%)
7,379 (41.6%)
-0.08
37,046 (40.1%)
18,250 (44.9%)
-0.10
58892 (39.2%)
31676 (43.2%)
-0.08
All antidiabetic medications except Insulin; n (%)
6,249 (24.3%)
3,472 (23.4%)
0.02
7,734 (23.9%)
4,459 (25.1%)
-0.03
26,614 (28.8%)
12,216 (30.1%)
-0.03
40597 (27.0%)
20147 (27.5%)
-0.01
DM Medications - Insulin Copy; n (%)
1,395 (5.4%)
653 (4.4%)
0.05
2,314 (7.2%)
1,089 (6.1%)
0.04
6,547 (7.1%)
2,810 (6.9%)
0.01
10256 (6.8%)
4552 (6.2%)
0.02
Use of Low Intensity Statins; n (%)
9,654 (37.6%)
4,898 (32.9%)
0.10
11,758 (36.4%)
5,834 (32.9%)
0.07
35,863 (38.8%)
14,698 (36.2%)
0.05
57275 (38.1%)
25430 (34.7%)
0.07
Use of High Intensity Statins; n (%)
5,758 (22.4%)
4,335 (29.2%)
-0.16
7,351 (22.8%)
4,764 (26.8%)
-0.09
21,260 (23.0%)
11,124 (27.4%)
-0.10
34369 (22.9%)
20223 (27.6%)
-0.11
Malignant hypertension; n (%)
1,402 (5.5%)
605 (4.1%)
0.07
14,434 (44.7%)
7,875 (44.4%)
0.01
24,773 (26.8%)
11,920 (29.3%)
-0.06
40609 (27.0%)
20400 (27.8%)
-0.02
Cardiovascular stress test; n (%)
119 (0.5%)
72 (0.5%)
0.00
232 (0.7%)
126 (0.7%)
0.00
901 (1.0%)
384 (0.9%)
0.01
1252 (0.8%)
582 (0.8%)
0.00
Echocardiogram; n (%)
9,046 (35.2%)
7,241 (48.7%)
-0.28
11,883 (36.8%)
9,419 (53.1%)
-0.33
41,768 (45.2%)
25,031 (61.6%)
-0.33
62697 (41.7%)
41691 (56.9%)
-0.31
Number of BNP tests
...mean (sd)
0.13 (0.49)
0.16 (0.53)
-0.06
0.08 (0.45)
0.10 (0.40)
-0.05
0.24 (0.66)
0.27 (0.66)
-0.05
0.19 (0.59)
0.21 (0.58)
-0.03
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 (0.66)
0.00 (0.62)
0.00
Number of Cardiac biomarkers tests (tropnin, CK-MBs, Myoglobin, CPK)
...mean (sd)
0.37 (1.26)
0.57 (1.61)
-0.14
0.27 (1.17)
0.47 (1.53)
-0.15
0.31 (0.65)
0.42 (0.75)
-0.16
0.31 (0.91)
0.46 (1.19)
0.00
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 [0.00, 0.00]
0.00 [0.00, 1.00]
0.00
0.00 (1.17)
0.00 (1.46)
0.00
Number of Ambulatory Blood pressure monitoring tests
...mean (sd)
0.00 (0.03)
0.00 (0.03)
0.00
0.00 (0.04)
0.00 (0.05)
0.00
0.00 (0.03)
0.00 (0.04)
0.00
0.00 (0.03)
0.00 (0.04)
0.00
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 (0.04)
0.00 (0.05)
0.00
N of days on antihypertensive medications during baseline
0
0
Appendix B: Rivaroxaban vs Warfarin

...mean (sd)
138.54 (63.34)
137.54 (63.50)
0.02
140.38 (63.02)
137.96 (64.23)
0.04
147.39 (56.03)
147.97 (55.26)
-0.01
144.37 (58.88)
143.43 (59.26)
0.00
...median [IQR]
174.00 [120.00, 181.00]
173.00 [116.00, 181.00]
0.02
177.00 [126.00, 181.00]
174.00 [119.00, 181.00]
0.05
177.00 [144.00, 181.00] 0 [145.00, 181.00]
0.02
105.75 (71.09)
119.89 (69.29)
0.00
N of days in database anytime prior
0
0
...mean (sd)
1,959.27 (1,297.23)
2,058.84 (1,433.06)
-0.07
2,420.20 (1,291.48)
2,541.09 (1,409.03)
-0.09
953.45 (634.65)
823.51 (522.94)
0.22
1440.28 (945.08)
1490.25 (1024.40)
0.00
...median [IQR]
1,776.00 [827.00, 
2,836.00]
1,720.00 [832.00, 
3,097.00]
0.0466.00 [1,252.00, 3,479.00]11.00 [1,278.00, 3,708.75]
0.04716.00 [478.00, 1,286.00] 0 [490.00, 961.00]
0.09
1008.23 (1248.91)
1117.65 (1292.30)
0.00
Mean Copay for per prescription cost (charges in U.S. $) (180-1 day prior)
0
0
...mean (sd)
28.47 (41.39)
29.22 (39.66)
-0.02
19.16 (19.36)
18.88 (20.59)
0.01
121.51 (113.74)
117.02 (103.79)
0.04
83.63 (91.22)
75.43 (79.99)
0.00
...median [IQR]
17.87 [8.00, 34.79]
18.85 [7.82, 36.19]
-0.02
15.00 [7.40, 25.46]
14.01 [6.55, 25.02]
0.05
99.09 [70.50, 141.51] 40 [68.67, 135.00]
0.03
27.55 (92.04)
30.33 (80.82)
0.00
...Missing; n (%)
697 (2.7%)
299 (2.0%)
0.05
831 (2.6%)
341 (1.9%)
0.05
1,655 (1.8%)
476 (1.2%)
0.05
3183 (2.1%)
1116 (1.5%)
0.05
Colonoscopy; n (%)
640 (2.5%)
432 (2.9%)
-0.02
868 (2.7%)
644 (3.6%)
-0.05
2,623 (2.8%)
1,364 (3.4%)
-0.03
4131 (2.7%)
2440 (3.3%)
-0.04
Fecal occult blood (FOB) test; n (%)
754 (2.9%)
493 (3.3%)
-0.02
598 (1.9%)
404 (2.3%)
-0.03
2,177 (2.4%)
1,058 (2.6%)
-0.01
3529 (2.3%)
1955 (2.7%)
-0.03
Flu vaccine; n (%)
5,240 (20.4%)
2,802 (18.8%)
0.04
4,338 (13.4%)
2,190 (12.3%)
0.03
30,438 (32.9%)
13,288 (32.7%)
0.00
40016 (26.6%)
18280 (24.9%)
0.04
Mammogram; n (%)
2,062 (8.0%)
1,374 (9.2%)
-0.04
1,495 (4.6%)
1,054 (5.9%)
-0.06
8,045 (8.7%)
3,965 (9.8%)
-0.04
11602 (7.7%)
6393 (8.7%)
-0.04
Pap smear; n (%)
305 (1.2%)
250 (1.7%)
-0.04
405 (1.3%)
358 (2.0%)
-0.05
1,287 (1.4%)
814 (2.0%)
-0.05
1997 (1.3%)
1422 (1.9%)
-0.05
Pneumonia vaccine; n (%)
3,034 (11.8%)
2,543 (17.1%)
-0.15
1,406 (4.4%)
1,266 (7.1%)
-0.12
14,621 (15.8%)
8,703 (21.4%)
-0.14
19061 (12.7%)
12512 (17.1%)
-0.12
PSA test or Prostate exam for DRE; n (%)
2,967 (11.5%)
2,054 (13.8%)
-0.07
1,970 (6.1%)
1,552 (8.7%)
-0.10
9,178 (9.9%)
4,445 (10.9%)
-0.03
14115 (9.4%)
8051 (11.0%)
-0.05
Bone mineral density; n (%)
805 (3.1%)
532 (3.6%)
-0.03
452 (1.4%)
276 (1.6%)
-0.02
3,027 (3.3%)
1,480 (3.6%)
-0.02
4284 (2.8%)
2288 (3.1%)
-0.02
Use of Sympatomimetic agents; n (%)
51 (0.2%)
60 (0.4%)
-0.04
104 (0.3%)
95 (0.5%)
-0.03
205 (0.2%)
119 (0.3%)
-0.02
360 (0.2%)
274 (0.4%)
-0.04
Use of CNS stimulants; n (%)
48 (0.2%)
45 (0.3%)
-0.02
111 (0.3%)
93 (0.5%)
-0.03
163 (0.2%)
109 (0.3%)
-0.02
322 (0.2%)
247 (0.3%)
-0.02
Use of estrogens, progestins, androgens; n (%)
559 (2.2%)
471 (3.2%)
-0.06
1,035 (3.2%)
806 (4.5%)
-0.07
2,155 (2.3%)
1,280 (3.1%)
-0.05
3749 (2.5%)
2557 (3.5%)
-0.06
Use of Angiogenesis inhibitors; n (%)
6 (0.0%)
4 (0.0%)
#DIV/0!
10 (0.0%)
5 (0.0%)
#DIV/0!
24 (0.0%)
14 (0.0%)
#DIV/0!
40 (0.0%)
23 (0.0%)
#DIV/0!
Use of Oral Immunosuppressants; n (%)
5 (0.0%)
1 (0.0%)
#DIV/0!
21 (0.1%)
7 (0.0%)
0.04
24 (0.0%)
**
#VALUE!
50 (0.0%)
#VALUE!
#VALUE!
Use of fondaparinux or Bivalirudin; n (%)
13 (0.1%)
1 (0.0%)
0.04
14 (0.0%)
3 (0.0%)
#DIV/0!
43 (0.0%)
11 (0.0%)
#DIV/0!
70 (0.0%)
15 (0.0%)
#DIV/0!
Use of other direct thrombin inhibitors (lepirudin, 
desirudin, argatroban); n (%)
0 (0.0%)
0 (0.0%)
#DIV/0!
0 (0.0%)
0 (0.0%)
#DIV/0!
0 (0.0%)
0 (0.0%)
#DIV/0!
0 (0.0%)
0 (0.0%)
#DIV/0!
Use of Ticagrelor ON CED; n (%)
18 (0.1%)
40 (0.3%)
-0.04
29 (0.1%)
29 (0.2%)
-0.03
30 (0.0%)
19 (0.0%)
#DIV/0!
77 (0.1%)
88 (0.1%)
0.00
Use of Ticagrelor; n (%)
33 (0.1%)
68 (0.5%)
-0.07
38 (0.1%)
48 (0.3%)
-0.04
208 (0.2%)
143 (0.4%)
-0.04
279 (0.2%)
259 (0.4%)
-0.04
Number of D-dimer tests
...mean (sd)
0.02 (0.17)
0.03 (0.21)
-0.05
0.01 (0.13)
0.03 (0.20)
-0.12
0.03 (0.19)
0.05 (0.23)
-0.09
0.02 (0.18)
0.04 (0.22)
0.00
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 (0.19)
0.00 (0.25)
0.00
Numbe of CRP, high-sensitivity CRP tests
...mean (sd)
0.05 (0.33)
0.07 (0.36)
-0.06
0.03 (0.23)
0.04 (0.27)
-0.04
0.08 (0.42)
0.10 (0.47)
-0.04
0.06 (0.37)
0.08 (0.41)
0.00
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 (0.40)
0.00 (0.44)
0.00
Number of PT or aPTTt tests
...mean (sd)
2.81 (4.00)
0.46 (1.30)
0.79
2.00 (3.43)
0.37 (1.15)
0.64
3.70 (4.84)
0.42 (1.13)
0.93
3.18 (4.43)
0.42 (1.17)
0.01
...median [IQR]
1.00 [0.00, 5.00]
0.00 [0.00, 0.00]
0.34
0.00 [0.00, 3.00]
0.00 [0.00, 0.00]
0.00
1.00 [0.00, 6.00]
0.00 [0.00, 1.00]
0.28
0.39 (4.94)
0.00 (1.34)
0.00
Number of Bleeding time tests
...mean (sd)
0.00 (0.01)
0.00 (0.00)
0.00
0.00 (0.00)
0.00 (0.02)
0.00
0.00 (0.01)
0.00 (0.01)
0.00
0.00 (0.01)
0.00 (0.01)
0.00
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 (0.01)
0.00 (0.02)
0.00
HAS-BLED Score (ICD-9 and ICD-10), 180 days
...mean (sd)
3.32 (0.71)
3.41 (0.80)
-0.12
3.23 (0.72)
3.24 (0.80)
-0.01
3.49 (0.71)
3.58 (0.74)
-0.12
3.41 (0.71)
3.46 (0.77)
0.00
...median [IQR]
3.00 [3.00, 4.00]
3.00 [3.00, 4.00]
0.00
3.00 [3.00, 4.00]
3.00 [3.00, 4.00]
0.00
3.00 [3.00, 4.00]
3.00 [3.00, 4.00]
0.00
1.80 (0.85)
2.06 (0.89)
0.00
N of Generic name drugs
...mean (sd)
18.50 (14.88)
18.50 (15.49)
0.00
14.58 (9.95)
14.60 (10.87)
0.00
19.40 (13.61)
20.44 (15.43)
-0.07
18.21 (13.15)
18.63 (14.47)
0.00
...median [IQR]
15.00 [9.00, 23.00]
15.00 [8.00, 24.00]
0.00
13.00 [8.00, 19.00]
12.00 [7.00, 19.00]
0.10
16.00 [10.00, 25.00]7.00 [10.00, 26.00]
-0.07
8.79 (14.58)
10.07 (15.70)
0.00
N of Brand name drugs
...mean (sd)
3.32 (4.93)
4.72 (5.32)
-0.27
4.08 (4.53)
5.12 (4.82)
-0.22
3.85 (5.03)
5.57 (6.03)
-0.31
3.81 (4.91)
5.29 (5.62)
0.00
...median [IQR]
2.00 [0.00, 5.00]
3.00 [1.00, 6.00]
-0.19
3.00 [1.00, 6.00]
4.00 [2.00, 7.00]
-0.21
2.00 [0.00, 6.00]
4.00 [2.00, 7.00]
-0.36
1.42 (5.68)
2.55 (6.23)
0.00
Use of clopidogrel ; n (%)
2,022 (7.9%)
1,719 (11.6%)
-0.12
2,811 (8.7%)
2,115 (11.9%)
-0.11
9,421 (10.2%)
5,719 (14.1%)
-0.12
14254 (9.5%)
9553 (13.0%)
-0.11
Systemic embolism; n (%)
223 (0.9%)
121 (0.8%)
0.01
237 (0.7%)
128 (0.7%)
0.00
1,013 (1.1%)
386 (0.9%)
0.02
1473 (1.0%)
635 (0.9%)
0.01
DVT; n (%)
93 (0.4%)
40 (0.3%)
0.02
90 (0.3%)
33 (0.2%)
0.02
1,966 (2.1%)
738 (1.8%)
0.02
2149 (1.4%)
811 (1.1%)
0.03
PE; n (%)
1 (0.0%)
1 (0.0%)
#DIV/0!
0 (0.0%)
0 (0.0%)
#DIV/0!
481 (0.5%)
186 (0.5%)
0.00
482 (0.3%)
187 (0.3%)
0.00
Diabetes: 1 inpatient or 2 outpatient claims within 
183 days ; n (%)
9,210 (35.8%)
4,979 (33.5%)
0.05
10,556 (32.7%)
5,685 (32.0%)
0.01
41,545 (45.0%)
18,260 (44.9%)
0.00
61311 (40.8%)
28924 (39.5%)
0.03
Intracranial or retroperitoneal hemorrhage: 1 
inpatient or 2 outpatient claims within 183 days ; n 
(%)
42 (0.2%)
20 (0.1%)
0.03
72 (0.2%)
20 (0.1%)
0.03
326 (0.4%)
114 (0.3%)
0.02
440 (0.3%)
154 (0.2%)
0.02
Peptic Ulcer Disease; n (%)
3,489 (13.6%)
2,703 (18.2%)
-0.13
2,889 (8.9%)
2,207 (12.4%)
-0.11
16,513 (17.9%)
9,656 (23.8%)
-0.15
22891 (15.2%)
14566 (19.9%)
-0.12
Upper GI bleed; n (%)
0 (0.0%)
0 (0.0%)
#DIV/0!
0 (0.0%)
0 (0.0%)
#DIV/0!
86 (0.1%)
31 (0.1%)
0.00
86 (0.1%)
31 (0.0%)
0.04
Lower/ unspecified GI bleed; n (%)
0 (0.0%)
0 (0.0%)
#DIV/0!
0 (0.0%)
0 (0.0%)
#DIV/0!
1,049 (1.1%)
509 (1.3%)
-0.02
1049 (0.7%)
509 (0.7%)
0.00
Urogenital bleed; n (%)
0 (0.0%)
1 (0.0%)
#DIV/0!
0 (0.0%)
0 (0.0%)
#DIV/0!
1,725 (1.9%)
729 (1.8%)
0.01
1725 (1.1%)
730 (1.0%)
0.01
Other bleeds; n (%)
4 (0.0%)
3 (0.0%)
#DIV/0!
0 (0.0%)
1 (0.0%)
#DIV/0!
969 (1.0%)
399 (1.0%)
0.00
973 (0.6%)
403 (0.6%)
0.00
Prior cancer; n (%)
2,927 (11.4%)
2,127 (14.3%)
-0.09
3,033 (9.4%)
1,750 (9.9%)
-0.02
11,109 (12.0%)
5,640 (13.9%)
-0.06
17069 (11.3%)
9517 (13.0%)
-0.05
Aspirin; n (%)
139 (0.5%)
154 (1.0%)
-0.06
357 (1.1%)
314 (1.8%)
-0.06
418 (0.5%)
266 (0.7%)
-0.03
914 (0.6%)
734 (1.0%)
-0.04
Appendix B: Rivaroxaban vs Warfarin

Aspirin/dipyridamole; n (%)
73 (0.3%)
55 (0.4%)
-0.02
159 (0.5%)
118 (0.7%)
-0.03
374 (0.4%)
237 (0.6%)
-0.03
606 (0.4%)
410 (0.6%)
-0.03
Other antiplatelet agents; n (%)
151 (0.6%)
69 (0.5%)
0.01
182 (0.6%)
103 (0.6%)
0.00
601 (0.7%)
289 (0.7%)
0.00
934 (0.6%)
461 (0.6%)
0.00
PGP inhibitors; n (%)
10,770 (41.9%)
6,482 (43.6%)
-0.03
14,437 (44.7%)
8,199 (46.2%)
-0.03
44,650 (48.3%)
20,953 (51.5%)
-0.06
69857 (46.4%)
35634 (48.6%)
-0.04
Other gastroprotective agents; n (%)
182 (0.7%)
140 (0.9%)
-0.02
301 (0.9%)
204 (1.1%)
-0.02
1,082 (1.2%)
671 (1.7%)
-0.04
1565 (1.0%)
1015 (1.4%)
-0.04
Number of lipid tests ordered
...mean (sd)
0.63 (0.82)
0.71 (0.84)
-0.10
0.27 (0.68)
0.40 (0.88)
-0.17
0.69 (0.83)
0.76 (0.89)
-0.08
0.59 (0.80)
0.66 (0.88)
0.00
...median [IQR]
0.00 [0.00, 1.00]
1.00 [0.00, 1.00]
-1.20
0.00 [0.00, 0.00]
0.00 [0.00, 1.00]
0.00
1.00 [0.00, 1.00]
1.00 [0.00, 1.00]
0.00
0.21 (0.91)
0.45 (1.01)
0.00
Proton pump inhibitor; n (%)
4,768 (18.6%)
3,236 (21.8%)
-0.08
6,352 (19.7%)
3,979 (22.4%)
-0.07
23,264 (25.2%)
11,663 (28.7%)
-0.08
34384 (22.9%)
18878 (25.8%)
-0.07
H2 receptor antagonist; n (%)
1,060 (4.1%)
632 (4.3%)
-0.01
1,125 (3.5%)
684 (3.9%)
-0.02
5,503 (6.0%)
2,836 (7.0%)
-0.04
7688 (5.1%)
4152 (5.7%)
-0.03
Vitamin K therapy; n (%)
20 (0.1%)
4 (0.0%)
0.04
57 (0.2%)
4 (0.0%)
0.06
119 (0.1%)
**
#VALUE!
196 (0.1%)
#VALUE!
#VALUE!
Number of neurologist visits
...mean (sd)
0.29 (1.48)
0.36 (1.49)
-0.05
0.23 (1.34)
0.27 (1.34)
-0.03
0.49 (2.00)
0.54 (2.01)
-0.02
0.40 (1.79)
0.44 (1.77)
0.00
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 (1.98)
0.00 (1.92)
0.00
Number of INR (prothrombin) tests ordered
...mean (sd)
2.68 (3.90)
0.29 (0.92)
0.84
1.90 (3.33)
0.23 (0.81)
0.69
3.68 (4.80)
0.39 (1.09)
0.95
3.13 (4.37)
0.33 (0.99)
0.01
...median [IQR]
1.00 [0.00, 5.00]
0.00 [0.00, 0.00]
0.35
0.00 [0.00, 2.00]
0.00 [0.00, 0.00]
0.00
1.00 [0.00, 6.00]
0.00 [0.00, 1.00]
0.29
0.39 (4.85)
0.00 (1.09)
0.00
Treating prescriber - Cardiologist; n (%)
12,149 (47.3%)
9,745 (65.5%)
-0.37
12,028 (37.2%)
10,681 (60.2%)
-0.47
46,370 (50.2%)
27,902 (68.6%)
-0.38
70547 (46.9%)
48328 (66.0%)
-0.39
Treating prescriber - Primary Care Physician; n (%)
16,835 (65.5%)
9,464 (63.6%)
0.04
9,639 (29.8%)
5,942 (33.5%)
-0.08
25,268 (27.3%)
12,084 (29.7%)
-0.05
51742 (34.4%)
27490 (37.5%)
-0.06
Treating prescriber - Other; n (%)
21,098 (82.1%)
12,821 (86.2%)
-0.11
24,503 (75.9%)
14,433 (81.3%)
-0.13
77,468 (83.8%)
36,185 (89.0%)
-0.15
123069 (81.8%)
63439 (86.6%)
-0.13
Alpha blockers; n (%)
3,114 (12.1%)
1,816 (12.2%)
0.00
4,170 (12.9%)
2,035 (11.5%)
0.04
11,524 (12.5%)
5,009 (12.3%)
0.01
18808 (12.5%)
8860 (12.1%)
0.01
CHADS2 score, 180 days, V
...mean (sd)
2.22 (1.17)
1.98 (1.19)
0.20
2.23 (1.18)
2.05 (1.20)
0.15
3.80 (1.61)
3.62 (1.65)
0.11
3.19 (1.46)
2.91 (1.47)
0.00
...median [IQR]
2.00 [1.00, 3.00]
2.00 [1.00, 3.00]
0.00
2.00 [1.00, 3.00]
2.00 [1.00, 3.00]
0.00
4.00 [3.00, 5.00]
3.00 [2.00, 5.00]
0.61
1.63 (1.64)
1.62 (1.61)
0.00
Use of Prasugrel; n (%)
43 (0.2%)
58 (0.4%)
-0.04
69 (0.2%)
88 (0.5%)
-0.05
**
**
#VALUE!
#VALUE!
#VALUE!
#VALUE!
Use of Loop Diuretics+other diuretics+other 
hypertension drugs; n (%)
9,459 (36.8%)
4,643 (31.2%)
0.12
12,825 (39.7%)
5,131 (28.9%)
0.23
45,778 (49.5%)
17,784 (43.7%)
0.12
68062 (45.3%)
27558 (37.6%)
0.16
Commercial vs Medicare Advantage- Business Type 
Code - CORRECT ONE - OPTUM
...Commercial; n (%)
3,292 (12.8%)
3244 (21.8%)
-0.24
27,877 (86.3%)
13,057 (73.6%)
0.32
-
-
#VALUE!
31,169 (53.7%)
16,301 (50.0%)
0.07
...Medicare Advantage; n (%)
22,409 (87.2%)
11625 (78.2%)
0.24
4,418 (13.7%)
4,691 (26.4%)
-0.32
-
-
#VALUE!
26,827 (46.3%)
16,316 (50.0%)
-0.07
Commercial vs Medicare Advantage- Business Type 
Code
...COM = COMMERCIAL; n (%)
3,292 (12.8%)
3,244 (21.8%)
-0.24
-
-
-
-
#VALUE!
3,292 (12.8%)
3,244 (21.8%)
-0.24
...MCR = MEDICARE; n (%)
22,409 (87.2%)
11,625 (78.2%)
0.24
-
-
-
-
#VALUE!
22,409 (87.2%)
11,625 (78.2%)
0.24
...MCD = MEDICAID; n (%)
0 (0.0%)
0 (0.0%)
#DIV/0!
-
-
-
-
#VALUE!
0 (0.0%)
0 (0.0%)
#DIV/0!
...NONE = NO BUSINESS LINE CODE (added in 2015); n 
(%)
0 (0.0%)
0 (0.0%)
#DIV/0!
-
-
-
-
#VALUE!
0 (0.0%)
0 (0.0%)
#DIV/0!
...UNK = UNKNOWN (added in 2015); n (%)
0 (0.0%)
0 (0.0%)
#DIV/0!
-
-
-
-
#VALUE!
0 (0.0%)
0 (0.0%)
#DIV/0!
Commercial vs Medicare Advantage- Data Type
...1 - Fee For Service; n (%)
-
-
3,872 (12.0%)
4,189 (23.6%)
-0.31
-
-
3,872 (12.0%)
4,189 (23.6%)
-0.31
...2 - Encounter; n (%)
-
-
546 (1.7%)
502 (2.8%)
-0.07
-
-
546 (1.7%)
502 (2.8%)
-0.07
...3 - Medicare; n (%)
-
-
25,005 (77.4%)
12,039 (67.8%)
0.22
-
-
25,005 (77.4%)
12,039 (67.8%)
0.22
...4 - Medicare Encounter; n (%)
-
-
2,872 (8.9%)
1,018 (5.7%)
0.12
-
-
2,872 (8.9%)
1,018 (5.7%)
0.12
Metropolitan Statistical Area - Urban (any MSA) vs 
Rural (non-MSA)
0
0
0.00
...Urban; n (%)
-
-
24,996 (77.4%)
12,798 (72.1%)
0.12
-
-
24,996 (77.4%)
12,798 (72.1%)
0.12
...Rural; n (%)
-
-
490 (1.5%)
680 (3.8%)
-0.14
-
-
490 (1.5%)
680 (3.8%)
-0.14
...Unknown/Missing; n (%)
-
-
6,809 (21.1%)
4,270 (24.1%)
-0.07
-
-
6,809 (21.1%)
4,270 (24.1%)
-0.07
Due to CMS cell suppression policy, all values less than 11 are 
denoted with **
Appendix B: Rivaroxaban vs Warfarin

Variable
Reference- warfarin
Exposure - rivaroxaban 
(15 or 20 mg)
St. Diff.
Reference- warfarin
Exposure - rivaroxaban 
(15 or 20 mg)
St. Diff.
Reference- warfarin
Exposure - rivaroxaban 
(15 or 20 mg)
St. Diff.
 Reference- warfarin 
 Exposure - rivaroxaban 
(15 or 20 mg) 
St. Diff.
Number of patients
8,950
                                            
8,950
                                            
11,300
                                         
11,300
                                         
31,068
                                         
31,068
                                         
                                          51,318                                           51,318 
Age
...mean (sd)
75.84 (8.34)
75.85 (8.57)
0.00
75.02 (10.73)
75.15 (10.38)
-0.01
78.73 (8.21)
78.77 (8.02)
0.00
77.41 (8.85)
77.46 (8.69)
-0.01
...median [IQR]
77.00 [71.00, 82.00]
77.00 [71.00, 82.00]
0.00
77.00 [68.00, 83.00]
77.00 [68.00, 83.00]
0.00
79.00 [74.00, 84.00]
79.00 [74.00, 84.00]
0.00
78.21 (8.85)
78.21 (8.69)
0.00
Age categories without zero category
...18 - 54; n (%)
198 (2.2%)
212 (2.4%)
-0.01
484 (4.3%)
371 (3.3%)
0.05
310 (1.0%)
298 (1.0%)
0.00
992 (1.9%)
881 (1.7%)
0.02
...55 - 64; n (%)
682 (7.6%)
723 (8.1%)
-0.02
1,629 (14.4%)
1,717 (15.2%)
-0.02
998 (3.2%)
923 (3.0%)
0.01
3,309 (6.4%)
3,363 (6.6%)
-0.01
...65 - 74; n (%)
2,239 (25.0%)
2,150 (24.0%)
0.02
2,325 (20.6%)
2,352 (20.8%)
0.00
6,715 (21.6%)
6,584 (21.2%)
0.01
11,279 (22.0%)
11,086 (21.6%)
0.01
...>= 75; n (%)
5,831 (65.2%)
5,865 (65.5%)
-0.01
6,862 (60.7%)
6,860 (60.7%)
0.00
23,045 (74.2%)
23,263 (74.9%)
-0.02
35,738 (69.6%)
35,988 (70.1%)
-0.01
Gender without zero category- United
...Males; n (%)
4,473 (50.0%)
4,535 (50.7%)
-0.01
6,033 (53.4%)
6,030 (53.4%)
0.00
12,637 (40.7%)
12,722 (40.9%)
0.00
23,143 (45.1%)
23,287 (45.4%)
-0.01
...Females; n (%)
4,477 (50.0%)
4,415 (49.3%)
0.01
5,267 (46.6%)
5,270 (46.6%)
0.00
18,431 (59.3%)
18,346 (59.1%)
0.00
28,175 (54.9%)
28,031 (54.6%)
0.01
Race 
...White; n (%)
28,382 (91.4%)
28,419 (91.5%)
28,382 (91.4%)
28,419 (91.5%)
0.00
...Black; n (%)
1,389 (4.5%)
1,354 (4.4%)
1,389 (4.5%)
1,354 (4.4%)
0.00
...Asian; n (%)
339 (1.1%)
333 (1.1%)
339 (1.1%)
333 (1.1%)
0.00
...Hispanic; n (%)
433 (1.4%)
421 (1.4%)
433 (1.4%)
421 (1.4%)
0.00
...North American Native; n (%)
133 (0.4%)
136 (0.4%)
133 (0.4%)
136 (0.4%)
0.00
...Other/Unknown; n (%)
392 (1.3%)
405 (1.3%)
392 (1.3%)
405 (1.3%)
0.00
Region without zero category- United v3 (lumping 
missing&other category with West)
...Northeast; n (%)
1,313 (14.7%)
1,310 (14.6%)
0.00
2,698 (23.9%)
2,762 (24.4%)
-0.01
6,528 (21.0%)
6,476 (20.8%)
0.00
10,539 (20.5%)
10,548 (20.6%)
0.00
...South; n (%)
3,278 (36.6%)
3,242 (36.2%)
0.01
3,425 (30.3%)
3,431 (30.4%)
0.00
11,305 (36.4%)
11,225 (36.1%)
0.01
18,008 (35.1%)
17,898 (34.9%)
0.00
...Midwest; n (%)
1,900 (21.2%)
1,902 (21.3%)
0.00
3,502 (31.0%)
3,436 (30.4%)
0.01
8,521 (27.4%)
8,630 (27.8%)
-0.01
13,923 (27.1%)
13,968 (27.2%)
0.00
...West; n (%)
2,459 (27.5%)
2,496 (27.9%)
-0.01
1,619 (14.3%)
1,608 (14.2%)
0.00
4,714 (15.2%)
4,737 (15.2%)
0.00
8,792 (17.1%)
8,841 (17.2%)
0.00
...Unknown+missing; n (%)
N/A
N/A
#VALUE!
56 (0.5%)
63 (0.6%)
-0.01
N/A
N/A
#VALUE!
56 (0.5%)
63 (0.6%)
-0.01
CV Covariates
Ischemic heart disease; n (%)
3,345 (37.4%)
3,391 (37.9%)
-0.01
4,174 (36.9%)
4,143 (36.7%)
0.00
13,673 (44.0%)
13,547 (43.6%)
0.01
21,192 (41.3%)
21,081 (41.1%)
0.00
Acute MI; n (%)
283 (3.2%)
286 (3.2%)
0.00
335 (3.0%)
321 (2.8%)
0.01
1,279 (4.1%)
1,279 (4.1%)
0.00
1897 (3.7%)
1886 (3.7%)
0.00
ACS/unstable angina; n (%)
260 (2.9%)
272 (3.0%)
-0.01
329 (2.9%)
314 (2.8%)
0.01
1,247 (4.0%)
1,204 (3.9%)
0.01
1836 (3.6%)
1790 (3.5%)
0.01
Old MI; n (%)
511 (5.7%)
520 (5.8%)
0.00
367 (3.2%)
368 (3.3%)
-0.01
2,737 (8.8%)
2,639 (8.5%)
0.01
3615 (7.0%)
3527 (6.9%)
0.00
Stable angina; n (%)
482 (5.4%)
502 (5.6%)
-0.01
456 (4.0%)
438 (3.9%)
0.01
1,541 (5.0%)
1,478 (4.8%)
0.01
2,479 (4.8%)
2,418 (4.7%)
0.00
Coronary atherosclerosis and other forms of chronic 
ischemic heart disease; n (%)
3,067 (34.3%)
3,086 (34.5%)
0.00
3,851 (34.1%)
3,793 (33.6%)
0.01
12,563 (40.4%)
12,456 (40.1%)
0.01
19,481 (38.0%)
19,335 (37.7%)
0.01
Other atherosclerosis with ICD10 v2 Copy; n (%)
142 (1.6%)
152 (1.7%)
-0.01
210 (1.9%)
212 (1.9%)
0.00
545 (1.8%)
561 (1.8%)
0.00
897 (1.7%)
925 (1.8%)
-0.01
Previous cardiac procedure (CABG or PTCA or Stent) 
v4; n (%)
119 (1.3%)
70 (0.8%)
0.05
164 (1.5%)
94 (0.8%)
0.07
581 (1.9%)
386 (1.2%)
0.06
864 (1.7%)
550 (1.1%)
0.05
History of CABG or PTCA; n (%)
862 (9.6%)
877 (9.8%)
-0.01
539 (4.8%)
614 (5.4%)
-0.03
4,822 (15.5%)
4,833 (15.6%)
0.00
6,223 (12.1%)
6,324 (12.3%)
-0.01
Any stroke; n (%)
1,763 (19.7%)
1,721 (19.2%)
0.01
2,030 (18.0%)
2,018 (17.9%)
0.00
6,768 (21.8%)
6,728 (21.7%)
0.00
10,561 (20.6%)
10,467 (20.4%)
0.00
Ischemic stroke (w and w/o mention of cerebral 
infarction); n (%)
1,763 (19.7%)
1,721 (19.2%)
0.01
2,030 (18.0%)
2,018 (17.9%)
0.00
6,754 (21.7%)
6,712 (21.6%)
0.00
10,547 (20.6%)
10,451 (20.4%)
0.00
Hemorrhagic stroke; n (%)
0 (0.0%)
0 (0.0%)
#DIV/0!
0 (0.0%)
0 (0.0%)
#DIV/0!
84 (0.3%)
82 (0.3%)
0.00
084 (0.2%)
82 (0.2%)
0.00
TIA; n (%)
691 (7.7%)
671 (7.5%)
0.01
830 (7.3%)
826 (7.3%)
0.00
2,093 (6.7%)
2,090 (6.7%)
0.00
3614 (7.0%)
3587 (7.0%)
0.00
Other cerebrovascular disease; n (%)
373 (4.2%)
358 (4.0%)
0.01
361 (3.2%)
359 (3.2%)
0.00
1,630 (5.2%)
1,585 (5.1%)
0.00
2364 (4.6%)
2302 (4.5%)
0.00
Late effects of cerebrovascular disease; n (%)
364 (4.1%)
365 (4.1%)
0.00
300 (2.7%)
293 (2.6%)
0.01
1,876 (6.0%)
1,871 (6.0%)
0.00
2540 (4.9%)
2529 (4.9%)
0.00
Cerebrovascular procedure; n (%)
14 (0.2%)
11 (0.1%)
0.03
20 (0.2%)
22 (0.2%)
0.00
100 (0.3%)
89 (0.3%)
0.00
134 (0.3%)
122 (0.2%)
0.02
Heart failure (CHF); n (%)
2,372 (26.5%)
2,375 (26.5%)
0.00
2,676 (23.7%)
2,699 (23.9%)
0.00
11,720 (37.7%)
11,670 (37.6%)
0.00
16,768 (32.7%)
16,744 (32.6%)
0.00
Peripheral Vascular Disease (PVD) or PVD Surgery v2; 
n (%)
912 (10.2%)
920 (10.3%)
0.00
1,016 (9.0%)
1,004 (8.9%)
0.00
3,753 (12.1%)
3,694 (11.9%)
0.01
5,681 (11.1%)
5,618 (10.9%)
0.01
Atrial fibrillation; n (%)
8,698 (97.2%)
8,704 (97.3%)
-0.01
11,051 (97.8%)
11,001 (97.4%)
0.03
30,164 (97.1%)
30,159 (97.1%)
0.00
49,913 (97.3%)
49,864 (97.2%)
0.01
Other cardiac dysrhythmia; n (%)
5,962 (66.6%)
5,864 (65.5%)
0.02
4,868 (43.1%)
4,794 (42.4%)
0.01
17,844 (57.4%)
17,748 (57.1%)
0.01
28,674 (55.9%)
28,406 (55.4%)
0.01
Cardiac conduction disorders; n (%)
923 (10.3%)
893 (10.0%)
0.01
908 (8.0%)
884 (7.8%)
0.01
3,351 (10.8%)
3,266 (10.5%)
0.01
5182 (10.1%)
5043 (9.8%)
0.01
Other CVD; n (%)
3,376 (37.7%)
3,320 (37.1%)
0.01
3,973 (35.2%)
3,931 (34.8%)
0.01
12,375 (39.8%)
12,267 (39.5%)
0.01
19,724 (38.4%)
19,518 (38.0%)
0.01
Diabetes-related complications
Diabetic retinopathy; n (%)
147 (1.6%)
162 (1.8%)
-0.02
161 (1.4%)
170 (1.5%)
-0.01
537 (1.7%)
554 (1.8%)
-0.01
#VALUE!
886 (1.7%)
#VALUE!
Diabetes with other ophthalmic manifestations; n 
(%)
15 (0.2%)
19 (0.2%)
0.00
139 (1.2%)
123 (1.1%)
0.01
356 (1.1%)
355 (1.1%)
0.00
510 (1.0%)
497 (1.0%)
0.00
Retinal detachment, vitreous hemorrhage, 
vitrectomy; n (%)
16 (0.2%)
21 (0.2%)
0.00
26 (0.2%)
21 (0.2%)
0.00
55 (0.2%)
65 (0.2%)
0.00
097 (0.2%)
107 (0.2%)
0.00
Retinal laser coagulation therapy; n (%)
12 (0.1%)
7 (0.1%)
0.00
27 (0.2%)
21 (0.2%)
0.00
61 (0.2%)
60 (0.2%)
0.00
100 (0.2%)
88 (0.2%)
0.00
Occurrence of Diabetic Neuropathy v2 Copy; n (%)
558 (6.2%)
583 (6.5%)
-0.01
534 (4.7%)
551 (4.9%)
-0.01
2,148 (6.9%)
2,163 (7.0%)
0.00
3240 (6.3%)
3297 (6.4%)
0.00
Occurrence of diabetic nephropathy V3 with ICD10 
Copy; n (%)
0 (0.0%)
0 (0.0%)
#DIV/0!
0 (0.0%)
0 (0.0%)
#DIV/0!
401 (1.3%)
415 (1.3%)
0.00
401 (0.8%)
415 (0.8%)
0.00
Hypoglycemia v2; n (%)
68 (0.8%)
85 (0.9%)
-0.01
146 (1.3%)
140 (1.2%)
0.01
850 (2.7%)
854 (2.7%)
0.00
1064 (2.1%)
1079 (2.1%)
0.00
 PS-matched
MarketScan
Medicare
POOLED
Optum
Appendix B: Rivaroxaban vs Warfarin

Hyperglycemia; n (%)
506 (5.7%)
490 (5.5%)
0.01
309 (2.7%)
294 (2.6%)
0.01
2,020 (6.5%)
1,960 (6.3%)
0.01
2835 (5.5%)
2744 (5.3%)
0.01
Disorders of fluid electrolyte and acid-base balance; n 
(%)
1,013 (11.3%)
976 (10.9%)
0.01
959 (8.5%)
934 (8.3%)
0.01
4,247 (13.7%)
4,163 (13.4%)
0.01
6219 (12.1%)
6073 (11.8%)
0.01
Diabetic ketoacidosis; n (%)
12 (0.1%)
15 (0.2%)
-0.03
18 (0.2%)
16 (0.1%)
0.03
67 (0.2%)
61 (0.2%)
0.00
97 (0.2%)
92 (0.2%)
0.00
Hyperosmolar hyperglycemic nonketotic syndrome 
(HONK); n (%)
7 (0.1%)
15 (0.2%)
-0.03
11 (0.1%)
9 (0.1%)
0.00
55 (0.2%)
58 (0.2%)
0.00
73 (0.1%)
82 (0.2%)
-0.03
Diabetes with peripheral circulatory disorders with 
ICD-10 v2 Copy; n (%)
290 (3.2%)
248 (2.8%)
0.02
248 (2.2%)
241 (2.1%)
0.01
1,408 (4.5%)
1,448 (4.7%)
-0.01
1946 (3.8%)
1937 (3.8%)
0.00
Diabetic Foot; n (%)
199 (2.2%)
181 (2.0%)
0.01
245 (2.2%)
242 (2.1%)
0.01
1,221 (3.9%)
1,196 (3.8%)
0.01
1665 (3.2%)
1619 (3.2%)
0.00
Gangrene v2; n (%)
10 (0.1%)
18 (0.2%)
-0.03
15 (0.1%)
9 (0.1%)
0.00
73 (0.2%)
66 (0.2%)
0.00
098 (0.2%)
93 (0.2%)
0.00
Lower extremity amputation; n (%)
40 (0.4%)
36 (0.4%)
0.00
16 (0.1%)
21 (0.2%)
-0.03
193 (0.6%)
163 (0.5%)
0.01
249 (0.5%)
220 (0.4%)
0.01
Osteomyelitis; n (%)
31 (0.3%)
29 (0.3%)
0.00
42 (0.4%)
47 (0.4%)
0.00
194 (0.6%)
207 (0.7%)
-0.01
267 (0.5%)
283 (0.6%)
-0.01
Skin infections v2; n (%)
480 (5.4%)
496 (5.5%)
0.00
706 (6.2%)
697 (6.2%)
0.00
2,223 (7.2%)
2,259 (7.3%)
0.00
3409 (6.6%)
3452 (6.7%)
0.00
Erectile dysfunction; n (%)
161 (1.8%)
156 (1.7%)
0.01
172 (1.5%)
179 (1.6%)
-0.01
238 (0.8%)
233 (0.7%)
0.01
571 (1.1%)
568 (1.1%)
0.00
Diabetes with unspecified complication; n (%)
144 (1.6%)
150 (1.7%)
-0.01
137 (1.2%)
137 (1.2%)
0.00
545 (1.8%)
515 (1.7%)
0.01
826 (1.6%)
802 (1.6%)
0.00
Diabetes mellitus without mention of complications; 
n (%)
3,162 (35.3%)
3,150 (35.2%)
0.00
3,738 (33.1%)
3,747 (33.2%)
0.00
13,515 (43.5%)
13,644 (43.9%)
-0.01
20,415 (39.8%)
20,541 (40.0%)
0.00
Hypertension: 1 inpatient or 2 outpatient claims 
within 365 days; n (%)
7,782 (86.9%)
7,761 (86.7%)
0.01
8,716 (77.1%)
8,716 (77.1%)
0.00
29,357 (94.5%)
29,270 (94.2%)
0.01
45,855 (89.4%)
45,747 (89.1%)
0.01
Hyperlipidemia v2; n (%)
5,766 (64.4%)
5,800 (64.8%)
-0.01
5,868 (51.9%)
5,812 (51.4%)
0.01
19,778 (63.7%)
19,631 (63.2%)
0.01
31,412 (61.2%)
31,243 (60.9%)
0.01
Edema; n (%)
1,034 (11.6%)
1,057 (11.8%)
-0.01
1,013 (9.0%)
960 (8.5%)
0.02
3,510 (11.3%)
3,503 (11.3%)
0.00
5557 (10.8%)
5520 (10.8%)
0.00
Renal Dysfunction (non-diabetic) v2; n (%)
4 (0.0%)
4 (0.0%)
#DIV/0!
11 (0.1%)
12 (0.1%)
0.00
1,202 (3.9%)
1,189 (3.8%)
0.01
1217 (2.4%)
1205 (2.3%)
0.01
Occurrence of acute renal disease v2; n (%)
3 (0.0%)
3 (0.0%)
#DIV/0!
11 (0.1%)
12 (0.1%)
0.00
162 (0.5%)
150 (0.5%)
0.00
176 (0.3%)
165 (0.3%)
0.00
Occurrence of chronic renal insufficiency; n (%)
0 (0.0%)
0 (0.0%)
#DIV/0!
0 (0.0%)
0 (0.0%)
#DIV/0!
666 (2.1%)
671 (2.2%)
-0.01
666 (1.3%)
671 (1.3%)
0.00
Chronic kidney disease v2; n (%)
0 (0.0%)
0 (0.0%)
#DIV/0!
0 (0.0%)
0 (0.0%)
#DIV/0!
629 (2.0%)
629 (2.0%)
0.00
629 (1.2%)
629 (1.2%)
0.00
CKD Stage 3-4; n (%)
0 (0.0%)
0 (0.0%)
#DIV/0!
0 (0.0%)
0 (0.0%)
#DIV/0!
458 (1.5%)
438 (1.4%)
0.01
458 (0.9%)
438 (0.9%)
0.00
Occurrence of hypertensive nephropathy; n (%)
0 (0.0%)
0 (0.0%)
#DIV/0!
0 (0.0%)
0 (0.0%)
#DIV/0!
184 (0.6%)
174 (0.6%)
0.00
184 (0.4%)
174 (0.3%)
0.02
Occurrence of miscellaneous renal insufficiency v2; n 
(%)
1 (0.0%)
1 (0.0%)
#DIV/0!
0 (0.0%)
0 (0.0%)
#DIV/0!
470 (1.5%)
471 (1.5%)
0.00
471 (0.9%)
472 (0.9%)
0.00
Glaucoma or cataracts v2; n (%)
1,894 (21.2%)
1,900 (21.2%)
0.00
2,536 (22.4%)
2,439 (21.6%)
0.02
6,537 (21.0%)
6,644 (21.4%)
-0.01
10,967 (21.4%)
10,983 (21.4%)
0.00
Cellulitis or abscess of toe; n (%)
118 (1.3%)
139 (1.6%)
-0.03
108 (1.0%)
111 (1.0%)
0.00
576 (1.9%)
566 (1.8%)
0.01
802 (1.6%)
816 (1.6%)
0.00
Foot ulcer; n (%)
202 (2.3%)
183 (2.0%)
0.02
254 (2.2%)
247 (2.2%)
0.00
1,089 (3.5%)
1,063 (3.4%)
0.01
1545 (3.0%)
1493 (2.9%)
0.01
Bladder stones; n (%)
4 (0.0%)
8 (0.1%)
-0.04
10 (0.1%)
11 (0.1%)
0.00
32 (0.1%)
38 (0.1%)
0.00
46 (0.1%)
57 (0.1%)
0.00
Kidney stones; n (%)
82 (0.9%)
90 (1.0%)
-0.01
115 (1.0%)
120 (1.1%)
-0.01
471 (1.5%)
470 (1.5%)
0.00
668 (1.3%)
680 (1.3%)
0.00
Urinary tract infections (UTIs); n (%)
863 (9.6%)
811 (9.1%)
0.02
866 (7.7%)
893 (7.9%)
-0.01
5,140 (16.5%)
5,099 (16.4%)
0.00
6,869 (13.4%)
6,803 (13.3%)
0.00
Dipstick urinalysis; n (%)
2,549 (28.5%)
2,577 (28.8%)
-0.01
2,309 (20.4%)
2,468 (21.8%)
-0.03
11,599 (37.3%)
12,095 (38.9%)
-0.03
16,457 (32.1%)
17,140 (33.4%)
-0.03
Non-dipstick urinalysis; n (%)
1,254 (14.0%)
1,189 (13.3%)
0.02
693 (6.1%)
660 (5.8%)
0.01
4,879 (15.7%)
4,740 (15.3%)
0.01
6,826 (13.3%)
6,589 (12.8%)
0.01
Urine function test; n (%)
241 (2.7%)
209 (2.3%)
0.03
443 (3.9%)
383 (3.4%)
0.03
1,175 (3.8%)
1,210 (3.9%)
-0.01
1859 (3.6%)
1802 (3.5%)
0.01
Cytology; n (%)
75 (0.8%)
105 (1.2%)
-0.04
128 (1.1%)
111 (1.0%)
0.01
613 (2.0%)
709 (2.3%)
-0.02
816 (1.6%)
925 (1.8%)
-0.02
Cystoscopy; n (%)
88 (1.0%)
77 (0.9%)
0.01
182 (1.6%)
136 (1.2%)
0.03
622 (2.0%)
648 (2.1%)
-0.01
892 (1.7%)
861 (1.7%)
0.00
Other Covariates
Liver disease; n (%)
0 (0.0%)
0 (0.0%)
#DIV/0!
0 (0.0%)
0 (0.0%)
#DIV/0!
366 (1.2%)
348 (1.1%)
0.01
366 (0.7%)
348 (0.7%)
0.00
Osteoarthritis; n (%)
1,847 (20.6%)
1,844 (20.6%)
0.00
1,933 (17.1%)
1,954 (17.3%)
-0.01
7,796 (25.1%)
7,776 (25.0%)
0.00
11576 (22.6%)
11574 (22.6%)
0.00
Other arthritis, arthropathies and musculoskeletal 
pain; n (%)
3,488 (39.0%)
3,487 (39.0%)
0.00
4,219 (37.3%)
4,209 (37.2%)
0.00
13,347 (43.0%)
13,256 (42.7%)
0.01
21054 (41.0%)
20952 (40.8%)
0.00
Dorsopathies; n (%)
1,992 (22.3%)
2,023 (22.6%)
-0.01
2,342 (20.7%)
2,342 (20.7%)
0.00
7,506 (24.2%)
7,495 (24.1%)
0.00
11840 (23.1%)
11860 (23.1%)
0.00
Fractures; n (%)
349 (3.9%)
340 (3.8%)
0.01
447 (4.0%)
480 (4.2%)
-0.01
1,787 (5.8%)
1,785 (5.7%)
0.00
2583 (5.0%)
2605 (5.1%)
0.00
Falls v2; n (%)
473 (5.3%)
478 (5.3%)
0.00
232 (2.1%)
227 (2.0%)
0.01
992 (3.2%)
1,011 (3.3%)
-0.01
1697 (3.3%)
1716 (3.3%)
0.00
Osteoporosis; n (%)
768 (8.6%)
746 (8.3%)
0.01
702 (6.2%)
709 (6.3%)
0.00
3,282 (10.6%)
3,320 (10.7%)
0.00
4752 (9.3%)
4775 (9.3%)
0.00
Hyperthyroidism; n (%)
124 (1.4%)
103 (1.2%)
0.02
109 (1.0%)
111 (1.0%)
0.00
430 (1.4%)
440 (1.4%)
0.00
663 (1.3%)
654 (1.3%)
0.00
Hypothyroidism v2; n (%)
1,709 (19.1%)
1,709 (19.1%)
0.00
1,606 (14.2%)
1,556 (13.8%)
0.01
4,788 (15.4%)
4,787 (15.4%)
0.00
8103 (15.8%)
8052 (15.7%)
0.00
Other disorders of thyroid gland V2; n (%)
334 (3.7%)
325 (3.6%)
0.01
373 (3.3%)
400 (3.5%)
-0.01
1,184 (3.8%)
1,157 (3.7%)
0.01
1891 (3.7%)
1882 (3.7%)
0.00
Depression; n (%)
753 (8.4%)
771 (8.6%)
-0.01
695 (6.2%)
716 (6.3%)
0.00
3,844 (12.4%)
3,846 (12.4%)
0.00
5292 (10.3%)
5333 (10.4%)
0.00
Anxiety; n (%)
874 (9.8%)
866 (9.7%)
0.00
659 (5.8%)
673 (6.0%)
-0.01
3,598 (11.6%)
3,556 (11.4%)
0.01
5131 (10.0%)
5095 (9.9%)
0.00
Sleep_Disorder; n (%)
726 (8.1%)
736 (8.2%)
0.00
1,294 (11.5%)
1,277 (11.3%)
0.01
2,776 (8.9%)
2,753 (8.9%)
0.00
4796 (9.3%)
4766 (9.3%)
0.00
Dementia; n (%)
684 (7.6%)
653 (7.3%)
0.01
618 (5.5%)
610 (5.4%)
0.00
3,305 (10.6%)
3,289 (10.6%)
0.00
4607 (9.0%)
4552 (8.9%)
0.00
Delirium; n (%)
171 (1.9%)
170 (1.9%)
0.00
164 (1.5%)
174 (1.5%)
0.00
1,074 (3.5%)
1,042 (3.4%)
0.01
1409 (2.7%)
1386 (2.7%)
0.00
Psychosis; n (%)
126 (1.4%)
117 (1.3%)
0.01
136 (1.2%)
142 (1.3%)
-0.01
734 (2.4%)
737 (2.4%)
0.00
996 (1.9%)
996 (1.9%)
0.00
Obesity; n (%)
1,384 (15.5%)
1,388 (15.5%)
0.00
1,122 (9.9%)
1,195 (10.6%)
-0.02
5,082 (16.4%)
4,996 (16.1%)
0.01
7588 (14.8%)
7579 (14.8%)
0.00
Overweight; n (%)
423 (4.7%)
421 (4.7%)
0.00
190 (1.7%)
179 (1.6%)
0.01
988 (3.2%)
1,015 (3.3%)
-0.01
1601 (3.1%)
1615 (3.1%)
0.00
Smoking; n (%)
1,515 (16.9%)
1,472 (16.4%)
0.01
801 (7.1%)
817 (7.2%)
0.00
8,813 (28.4%)
8,655 (27.9%)
0.01
11129 (21.7%)
10944 (21.3%)
0.01
Alcohol abuse or dependence; n (%)
0 (0.0%)
0 (0.0%)
#DIV/0!
0 (0.0%)
0 (0.0%)
#DIV/0!
24 (0.1%)
22 (0.1%)
0.00
24 (0.0%)
22 (0.0%)
#DIV/0!
Drug abuse or dependence; n (%)
0 (0.0%)
0 (0.0%)
#DIV/0!
0 (0.0%)
0 (0.0%)
#DIV/0!
72 (0.2%)
62 (0.2%)
0.00
72 (0.1%)
62 (0.1%)
0.00
COPD; n (%)
1,561 (17.4%)
1,567 (17.5%)
0.00
1,692 (15.0%)
1,671 (14.8%)
0.01
6,895 (22.2%)
6,863 (22.1%)
0.00
10148 (19.8%)
10101 (19.7%)
0.00
Asthma; n (%)
627 (7.0%)
613 (6.8%)
0.01
701 (6.2%)
692 (6.1%)
0.00
2,585 (8.3%)
2,551 (8.2%)
0.00
3913 (7.6%)
3856 (7.5%)
0.00
Obstructive sleep apnea; n (%)
1,002 (11.2%)
991 (11.1%)
0.00
1,245 (11.0%)
1,186 (10.5%)
0.02
3,001 (9.7%)
2,961 (9.5%)
0.01
5248 (10.2%)
5138 (10.0%)
0.01
Pneumonia; n (%)
583 (6.5%)
564 (6.3%)
0.01
757 (6.7%)
774 (6.8%)
0.00
3,435 (11.1%)
3,386 (10.9%)
0.01
4775 (9.3%)
4724 (9.2%)
0.00
Imaging; n (%)
13 (0.1%)
12 (0.1%)
0.00
17 (0.2%)
14 (0.1%)
0.03
166 (0.5%)
132 (0.4%)
0.01
196 (0.4%)
158 (0.3%)
0.02
Other Medications
Appendix B: Rivaroxaban vs Warfarin

Use of ACE inhibitors; n (%)
3,302 (36.9%)
3,351 (37.4%)
-0.01
4,037 (35.7%)
4,053 (35.9%)
0.00
12,056 (38.8%)
12,104 (39.0%)
0.00
19395 (37.8%)
19508 (38.0%)
0.00
Use of ARBs; n (%)
2,148 (24.0%)
2,097 (23.4%)
0.01
2,946 (26.1%)
2,929 (25.9%)
0.00
7,885 (25.4%)
7,901 (25.4%)
0.00
12979 (25.3%)
12927 (25.2%)
0.00
Use of Loop Diuretics - United; n (%)
2,452 (27.4%)
2,457 (27.5%)
0.00
3,074 (27.2%)
2,962 (26.2%)
0.02
12,075 (38.9%)
12,145 (39.1%)
0.00
17601 (34.3%)
17564 (34.2%)
0.00
Use of other diuretics- United; n (%)
499 (5.6%)
452 (5.1%)
0.02
678 (6.0%)
628 (5.6%)
0.02
2,204 (7.1%)
2,206 (7.1%)
0.00
3381 (6.6%)
3286 (6.4%)
0.01
Use of nitrates-United; n (%)
721 (8.1%)
639 (7.1%)
0.04
1,067 (9.4%)
937 (8.3%)
0.04
3,909 (12.6%)
3,522 (11.3%)
0.04
5697 (11.1%)
5098 (9.9%)
0.04
Use of other hypertension drugs; n (%)
658 (7.4%)
690 (7.7%)
-0.01
798 (7.1%)
953 (8.4%)
-0.05
2,616 (8.4%)
2,741 (8.8%)
-0.01
4072 (7.9%)
4384 (8.5%)
-0.02
Use of digoxin- United; n (%)
1,060 (11.8%)
907 (10.1%)
0.05
1,932 (17.1%)
1,413 (12.5%)
0.13
4,898 (15.8%)
4,232 (13.6%)
0.06
7890 (15.4%)
6552 (12.8%)
0.07
Use of Anti-arrhythmics; n (%)
1,039 (11.6%)
1,022 (11.4%)
0.01
1,549 (13.7%)
1,578 (14.0%)
-0.01
3,969 (12.8%)
4,042 (13.0%)
-0.01
6557 (12.8%)
6642 (12.9%)
0.00
Use of COPD/asthma meds- United; n (%)
1,652 (18.5%)
1,660 (18.5%)
0.00
2,257 (20.0%)
2,211 (19.6%)
0.01
7,164 (23.1%)
6,884 (22.2%)
0.02
11073 (21.6%)
10755 (21.0%)
0.01
Use of statins; n (%)
5,403 (60.4%)
5,381 (60.1%)
0.01
6,725 (59.5%)
6,779 (60.0%)
-0.01
18,970 (61.1%)
19,049 (61.3%)
0.00
31098 (60.6%)
31209 (60.8%)
0.00
Use of other lipid-lowering drugs; n (%)
561 (6.3%)
570 (6.4%)
0.00
1,042 (9.2%)
1,077 (9.5%)
-0.01
2,197 (7.1%)
2,209 (7.1%)
0.00
3800 (7.4%)
3856 (7.5%)
0.00
Use of antiplatelet agents; n (%)
1,266 (14.1%)
1,275 (14.2%)
0.00
1,925 (17.0%)
1,862 (16.5%)
0.01
5,449 (17.5%)
5,400 (17.4%)
0.00
8640 (16.8%)
8537 (16.6%)
0.01
Use of heparin and other low-molecular weight 
heparins; n (%)
28 (0.3%)
48 (0.5%)
-0.03
1 (0.0%)
2 (0.0%)
#DIV/0!
191 (0.6%)
270 (0.9%)
-0.03
220 (0.4%)
320 (0.6%)
-0.03
Use of NSAIDs; n (%)
1,022 (11.4%)
1,003 (11.2%)
0.01
1,228 (10.9%)
1,245 (11.0%)
0.00
3,906 (12.6%)
3,909 (12.6%)
0.00
6156 (12.0%)
6157 (12.0%)
0.00
Use of oral corticosteroids; n (%)
1,770 (19.8%)
1,758 (19.6%)
0.01
2,198 (19.5%)
2,216 (19.6%)
0.00
7,748 (24.9%)
7,700 (24.8%)
0.00
11716 (22.8%)
11674 (22.7%)
0.00
Use of bisphosphonate (United); n (%)
341 (3.8%)
337 (3.8%)
0.00
381 (3.4%)
380 (3.4%)
0.00
1,209 (3.9%)
1,234 (4.0%)
-0.01
1931 (3.8%)
1951 (3.8%)
0.00
Use of opioids- United; n (%)
2,033 (22.7%)
2,065 (23.1%)
-0.01
2,709 (24.0%)
2,735 (24.2%)
0.00
9,005 (29.0%)
8,989 (28.9%)
0.00
13747 (26.8%)
13789 (26.9%)
0.00
Use of antidepressants; n (%)
1,849 (20.7%)
1,855 (20.7%)
0.00
2,139 (18.9%)
2,136 (18.9%)
0.00
8,280 (26.7%)
8,229 (26.5%)
0.00
12268 (23.9%)
12220 (23.8%)
0.00
Use of antipsychotics; n (%)
157 (1.8%)
157 (1.8%)
0.00
161 (1.4%)
157 (1.4%)
0.00
956 (3.1%)
931 (3.0%)
0.01
1274 (2.5%)
1245 (2.4%)
0.01
Use of anticonvulsants; n (%)
1,091 (12.2%)
1,112 (12.4%)
-0.01
1,164 (10.3%)
1,145 (10.1%)
0.01
4,966 (16.0%)
4,964 (16.0%)
0.00
7221 (14.1%)
7221 (14.1%)
0.00
Use of lithium- United; n (%)
4 (0.0%)
6 (0.1%)
-0.04
10 (0.1%)
12 (0.1%)
0.00
**
23 (0.1%)
#VALUE!
#VALUE!
41 (0.1%)
#VALUE!
Use of Benzos- United; n (%)
1,012 (11.3%)
1,061 (11.9%)
-0.02
1,532 (13.6%)
1,498 (13.3%)
0.01
4,482 (14.4%)
4,481 (14.4%)
0.00
7026 (13.7%)
7040 (13.7%)
0.00
Use of anxiolytics/hypnotics- United; n (%)
479 (5.4%)
469 (5.2%)
0.01
743 (6.6%)
762 (6.7%)
0.00
2,166 (7.0%)
2,139 (6.9%)
0.00
3388 (6.6%)
3370 (6.6%)
0.00
Use of dementia meds- United; n (%)
340 (3.8%)
346 (3.9%)
-0.01
407 (3.6%)
409 (3.6%)
0.00
1,688 (5.4%)
1,700 (5.5%)
0.00
2435 (4.7%)
2455 (4.8%)
0.00
Use of antiparkinsonian meds- United; n (%)
236 (2.6%)
245 (2.7%)
-0.01
317 (2.8%)
306 (2.7%)
0.01
1,223 (3.9%)
1,253 (4.0%)
-0.01
1776 (3.5%)
1804 (3.5%)
0.00
Any use of pramlintide; n (%)
1 (0.0%)
3 (0.0%)
#DIV/0!
2 (0.0%)
1 (0.0%)
#DIV/0!
**
**
#VALUE!
#VALUE!
#VALUE!
#VALUE!
Any use of 1st generation sulfonylureas; n (%)
0 (0.0%)
0 (0.0%)
#DIV/0!
1 (0.0%)
0 (0.0%)
#DIV/0!
**
**
#VALUE!
#VALUE!
#VALUE!
0.00
Entresto (sacubitril/valsartan); n (%)
38 (0.4%)
22 (0.2%)
0.04
15 (0.1%)
6 (0.1%)
0.00
35 (0.1%)
43 (0.1%)
0.00
88 (0.2%)
71 (0.1%)
0.00
Labs
                                          20,250                                           20,250 
Lab values- HbA1c (%) v3; n (%)
1,433 (16.0%)
1,474 (16.5%)
-0.01
137 (1.2%)
124 (1.1%)
0.01
N/A
N/A
#VALUE!
1,570 (7.8%)
1,598 (7.9%)
0.00
Lab values- HbA1c (%) (within 3 months) v3; n (%)
941 (10.5%)
955 (10.7%)
-0.01
98 (0.9%)
89 (0.8%)
0.01
N/A
N/A
#VALUE!
1,039 (5.1%)
1,044 (5.2%)
0.00
Lab values- HbA1c (%) (within 6 months) v3; n (%)
1,433 (16.0%)
1,474 (16.5%)
-0.01
137 (1.2%)
124 (1.1%)
0.01
N/A
N/A
#VALUE!
1,570 (7.8%)
1,598 (7.9%)
0.00
Lab values- BNP; n (%)
154 (1.7%)
168 (1.9%)
-0.02
18 (0.2%)
16 (0.1%)
0.03
N/A
N/A
#VALUE!
172 (0.8%)
184 (0.9%)
-0.01
Lab values- BNP (within 3 months); n (%)
114 (1.3%)
132 (1.5%)
-0.02
16 (0.1%)
11 (0.1%)
0.00
N/A
N/A
#VALUE!
130 (0.6%)
143 (0.7%)
-0.01
Lab values- BNP (within 6 months); n (%)
154 (1.7%)
168 (1.9%)
-0.02
18 (0.2%)
16 (0.1%)
0.03
N/A
N/A
#VALUE!
172 (0.8%)
184 (0.9%)
-0.01
Lab values- BUN (mg/dl); n (%)
2,374 (26.5%)
2,650 (29.6%)
-0.07
167 (1.5%)
206 (1.8%)
-0.02
N/A
N/A
#VALUE!
2,541 (12.5%)
2,856 (14.1%)
-0.05
Lab values- BUN (mg/dl) (within 3 months); n (%)
1,640 (18.3%)
1,900 (21.2%)
-0.07
121 (1.1%)
156 (1.4%)
-0.03
N/A
N/A
#VALUE!
1,761 (8.7%)
2,056 (10.2%)
-0.05
Lab values- BUN (mg/dl) (within 6 months); n (%)
2,374 (26.5%)
2,650 (29.6%)
-0.07
167 (1.5%)
206 (1.8%)
-0.02
N/A
N/A
#VALUE!
2,541 (12.5%)
2,856 (14.1%)
-0.05
Lab values- Creatinine (mg/dl) v2; n (%)
2,429 (27.1%)
2,743 (30.6%)
-0.08
171 (1.5%)
220 (1.9%)
-0.03
N/A
N/A
#VALUE!
2,600 (12.8%)
2,963 (14.6%)
-0.05
Lab values- Creatinine (mg/dl) (within 3 months) v2; 
n (%)
1,676 (18.7%)
1,980 (22.1%)
-0.08
124 (1.1%)
168 (1.5%)
-0.04
N/A
N/A
#VALUE!
1,800 (8.9%)
2,148 (10.6%)
-0.06
Lab values- Creatinine (mg/dl) (within 6 months) v2; 
n (%)
2,429 (27.1%)
2,743 (30.6%)
-0.08
171 (1.5%)
220 (1.9%)
-0.03
N/A
N/A
#VALUE!
2,600 (12.8%)
2,963 (14.6%)
-0.05
Lab values- HDL level (mg/dl); n (%)
1,739 (19.4%)
1,872 (20.9%)
-0.04
123 (1.1%)
132 (1.2%)
-0.01
N/A
N/A
#VALUE!
1,862 (9.2%)
2,004 (9.9%)
-0.02
Lab values- HDL level (mg/dl) (within 3 months); n (%)
1,100 (12.3%)
1,168 (13.1%)
-0.02
87 (0.8%)
90 (0.8%)
0.00
N/A
N/A
#VALUE!
1,187 (5.9%)
1,258 (6.2%)
-0.01
Lab values- HDL level (mg/dl) (within 6 months); n (%)
1,739 (19.4%)
1,872 (20.9%)
-0.04
123 (1.1%)
132 (1.2%)
-0.01
N/A
N/A
#VALUE!
1,862 (9.2%)
2,004 (9.9%)
-0.02
Lab values- LDL level (mg/dl) v2; n (%)
1,819 (20.3%)
1,948 (21.8%)
-0.04
146 (1.3%)
140 (1.2%)
0.01
N/A
N/A
#VALUE!
1,965 (9.7%)
2,088 (10.3%)
-0.02
Lab values- LDL level (mg/dl) (within 3 months) v2; n 
(%)
1,160 (13.0%)
1,220 (13.6%)
-0.02
104 (0.9%)
94 (0.8%)
0.01
N/A
N/A
#VALUE!
1,264 (6.2%)
1,314 (6.5%)
-0.01
Lab values- LDL level (mg/dl) (within 6 months) v2; n 
(%)
1,819 (20.3%)
1,948 (21.8%)
-0.04
146 (1.3%)
140 (1.2%)
0.01
N/A
N/A
#VALUE!
1,965 (9.7%)
2,088 (10.3%)
-0.02
Lab values- NT-proBNP; n (%)
15 (0.2%)
22 (0.2%)
0.00
5 (0.0%)
2 (0.0%)
#DIV/0!
N/A
N/A
#VALUE!
20 (0.1%)
24 (0.1%)
0.00
Lab values- NT-proBNP (within 3 months); n (%)
13 (0.1%)
19 (0.2%)
-0.03
2 (0.0%)
1 (0.0%)
#DIV/0!
N/A
N/A
#VALUE!
15 (0.1%)
20 (0.1%)
-
Lab values- NT-proBNP (within 6 months); n (%)
15 (0.2%)
22 (0.2%)
0.00
5 (0.0%)
2 (0.0%)
#DIV/0!
N/A
N/A
#VALUE!
20 (0.1%)
24 (0.1%)
-
Lab values- Total cholesterol (mg/dl) v2; n (%)
1,765 (19.7%)
1,886 (21.1%)
-0.03
119 (1.1%)
131 (1.2%)
-0.01
N/A
N/A
#VALUE!
1,884 (9.3%)
2,017 (10.0%)
-0.02
Lab values- Total cholesterol (mg/dl) (within 3 
months) v2; n (%)
1,122 (12.5%)
1,179 (13.2%)
-0.02
83 (0.7%)
89 (0.8%)
-0.01
N/A
N/A
#VALUE!
1,205 (6.0%)
1,268 (6.3%)
-0.01
Lab values- Total cholesterol (mg/dl) (within 6 
months) v2; n (%)
1,765 (19.7%)
1,886 (21.1%)
-0.03
119 (1.1%)
131 (1.2%)
-0.01
N/A
N/A
#VALUE!
1,884 (9.3%)
2,017 (10.0%)
-0.02
Lab values- Triglyceride level (mg/dl); n (%)
1,734 (19.4%)
1,874 (20.9%)
-0.04
121 (1.1%)
132 (1.2%)
-0.01
N/A
N/A
#VALUE!
1,855 (9.2%)
2,006 (9.9%)
-0.02
Lab values- Triglyceride level (mg/dl) (within 3 
months); n (%)
1,100 (12.3%)
1,170 (13.1%)
-0.02
86 (0.8%)
90 (0.8%)
0.00
N/A
N/A
#VALUE!
1,186 (5.9%)
1,260 (6.2%)
-0.01
Lab values- Triglyceride level (mg/dl) (within 6 
months); n (%)
1,734 (19.4%)
1,874 (20.9%)
-0.04
121 (1.1%)
132 (1.2%)
-0.01
N/A
N/A
#VALUE!
1,855 (9.2%)
2,006 (9.9%)
-0.02
Lab result number- HbA1c (%) mean (only 2 to 20 
included) v4
1,416
                                            
1,466
                                            
122
                                                
122
                                                
N/A
N/A
                                             1,538                                              1,588 
Appendix B: Rivaroxaban vs Warfarin

...mean (sd)
6.48 (1.08)
6.51 (1.20)
-0.03
6.91 (1.38)
6.62 (1.12)
0.23
N/A
N/A
#VALUE!
6.51 (1.11)
6.52 (1.19)
-0.01
...median [IQR]
6.20 [5.80, 6.90]
6.20 [5.80, 6.90]
0.00
6.50 [6.00, 7.53]
6.50 [6.00, 7.20]
0.00
N/A
N/A
#VALUE!
6.22 (1.11)
6.22 (1.19)
0.00
...Missing; n (%)
7,534 (84.2%)
7,484 (83.6%)
0.02
11,178 (98.9%)
11,178 (98.9%)
0.00
N/A
N/A
#VALUE!
18,712 (92.4%)
18,662 (92.2%)
0.01
Lab result number- BNP mean v2
154
                                                
168
                                                
18
                                                   
16
                                                   
N/A
N/A
                                                 172                                                  184 
...mean (sd)
341.80 (493.50)
331.40 (517.59)
0.02
513.00 (1,035.89)
408.20 (481.08)
0.13
N/A
N/A
#VALUE!
359.72 (573.09)
338.08 (516.10)
0.04
...median [IQR]
208.70 [104.59, 362.50]
225.62 [98.17, 371.25]
-0.03
148.50 [52.00, 353.00]
237.25 [100.00, 415.75]
-0.11
N/A
N/A
#VALUE!
202.40 (573.09)
226.63 (516.10)
-0.04
...Missing; n (%)
8,796 (98.3%)
8,782 (98.1%)
0.02
11,282 (99.8%)
11,284 (99.9%)
-0.03
N/A
N/A
#VALUE!
20,078 (99.2%)
20,066 (99.1%)
0.01
Lab result number- BUN (mg/dl) mean v2
                                             2,374                                              2,650 
                                                 167                                                  206 
N/A
N/A
                                             2,541                                              2,856 
...mean (sd)
18.15 (6.34)
18.15 (6.10)
0.00
17.73 (6.63)
20.03 (6.83)
-0.34
N/A
N/A
#VALUE!
18.12 (6.36)
18.29 (6.16)
-0.03
...median [IQR]
17.00 [14.00, 21.00]
17.00 [14.00, 21.00]
0.00
17.50 [14.00, 21.00]
18.38 [16.00, 23.00]
-0.13
N/A
N/A
#VALUE!
17.03 (6.36)
17.10 (6.16)
-0.01
...Missing; n (%)
6,576 (73.5%)
6,300 (70.4%)
0.07
11,133 (98.5%)
11,094 (98.2%)
0.02
N/A
N/A
#VALUE!
17,709 (87.5%)
17,394 (85.9%)
0.05
Lab result number- Creatinine (mg/dl) mean (only 0.1 
to 15 included) v3
                                             2,407                                              2,715 
                                                 166                                                  218 
N/A
N/A
                                             2,573                                              2,933 
...mean (sd)
0.97 (0.24)
0.96 (0.24)
0.04
0.98 (0.22)
1.00 (0.24)
-0.09
N/A
N/A
#VALUE!
0.97 (0.24)
0.96 (0.24)
0.04
...median [IQR]
0.94 [0.80, 1.10]
0.94 [0.81, 1.09]
0.00
0.98 [0.82, 1.11]
0.99 [0.81, 1.14]
-0.04
N/A
N/A
#VALUE!
0.94 (0.24)
0.94 (0.24)
0.00
...Missing; n (%)
6,543 (73.1%)
6,235 (69.7%)
0.08
11,134 (98.5%)
11,082 (98.1%)
0.03
N/A
N/A
#VALUE!
17,677 (87.3%)
17,317 (85.5%)
0.05
Lab result number- HDL level (mg/dl) mean (only 
=<5000 included) v2
                                             1,739                                              1,872 
                                                 123                                                  132 
N/A
N/A
                                             1,862                                              2,004 
...mean (sd)
51.74 (16.26)
52.61 (16.33)
-0.05
44.07 (17.47)
48.84 (15.34)
-0.29
N/A
N/A
#VALUE!
51.23 (16.35)
52.36 (16.27)
-0.07
...median [IQR]
49.50 [40.00, 60.00]
50.00 [41.00, 62.00]
-0.03
43.00 [34.00, 52.00]
48.75 [37.00, 57.00]
-0.35
N/A
N/A
#VALUE!
49.07 (16.35)
49.92 (16.27)
-0.05
...Missing; n (%)
7,211 (80.6%)
7,078 (79.1%)
0.04
11,177 (98.9%)
11,168 (98.8%)
0.01
N/A
N/A
#VALUE!
18,388 (90.8%)
18,246 (90.1%)
0.02
Lab result number- LDL level (mg/dl) mean (only 
=<5000 included) v2
                                             1,776                                              1,911 
                                                 120                                                  137 
N/A
N/A
                                             1,896                                              2,048 
...mean (sd)
88.73 (32.54)
86.79 (32.88)
0.06
83.58 (33.64)
88.09 (35.90)
-0.13
N/A
N/A
#VALUE!
88.40 (32.62)
86.88 (33.10)
0.05
...median [IQR]
85.00 [67.00, 108.00]
83.00 [64.00, 104.00]
0.06
81.00 [62.25, 103.38]
84.00 [64.00, 113.00]
-0.09
N/A
N/A
#VALUE!
84.75 (32.62)
83.07 (33.10)
0.05
...Missing; n (%)
7,174 (80.2%)
7,039 (78.6%)
0.04
11,180 (98.9%)
11,163 (98.8%)
0.01
N/A
N/A
#VALUE!
18,354 (90.6%)
18,202 (89.9%)
0.02
Lab result number- Total cholesterol (mg/dl) mean 
(only =<5000 included) v2
                                             1,763                                              1,884 
                                                 119                                                  131 
N/A
N/A
                                             1,882                                              2,015 
...mean (sd)
165.93 (40.58)
165.05 (40.64)
0.02
155.14 (47.10)
162.30 (41.22)
-0.16
N/A
N/A
#VALUE!
165.25 (41.03)
164.87 (40.69)
0.01
...median [IQR]
161.00 [139.00, 190.00]
161.00 [137.00, 188.00]
0.00
158.00 [134.00, 184.00]
159.00 [131.00, 194.00]
-0.02
N/A
N/A
#VALUE!
160.81 (41.03)
160.87 (40.69)
0.00
...Missing; n (%)
7,187 (80.3%)
7,066 (78.9%)
0.03
11,181 (98.9%)
11,169 (98.8%)
0.01
N/A
N/A
#VALUE!
18,368 (90.7%)
18,235 (90.0%)
0.02
Lab result number- Triglyceride level (mg/dl) mean 
(only =<5000 included) v2
                                             1,734                                              1,874 
                                                 121                                                  132 
N/A
N/A
                                             1,855                                              2,006 
...mean (sd)
128.92 (81.96)
125.55 (76.48)
0.04
134.40 (74.12)
124.14 (58.72)
0.15
N/A
N/A
#VALUE!
129.28 (81.50)
125.46 (75.47)
0.05
...median [IQR]
112.00 [82.38, 151.62]
107.00 [79.00, 149.25]
0.06
116.50 [84.50, 179.00]
117.00 [78.25, 150.00]
-0.01
N/A
N/A
#VALUE!
112.29 (81.50)
107.66 (75.47)
0.06
...Missing; n (%)
7,216 (80.6%)
7,076 (79.1%)
0.04
11,179 (98.9%)
11,168 (98.8%)
0.01
N/A
N/A
#VALUE!
18,395 (90.8%)
18,244 (90.1%)
0.02
Lab result number- Hemoglobin mean (only >0 
included)
                                             1,772                                              2,003 
                                                 127                                                  147 
N/A
N/A
                                             1,899                                              2,150 
...mean (sd)
13.68 (1.53)
13.75 (1.63)
-0.04
13.23 (2.25)
13.71 (1.67)
-0.24
N/A
N/A
#VALUE!
13.65 (1.59)
13.75 (1.63)
-0.06
...median [IQR]
13.65 [12.70, 14.70]
13.80 [12.75, 14.80]
-0.09
13.40 [12.30, 14.60]
13.80 [12.70, 14.70]
-0.20
N/A
N/A
#VALUE!
13.63 (1.59)
13.80 (1.63)
-0.11
...Missing; n (%)
7,178 (80.2%)
6,947 (77.6%)
0.06
11,173 (98.9%)
11,153 (98.7%)
0.02
N/A
N/A
#VALUE!
18,351 (90.6%)
18,100 (89.4%)
0.04
Lab result number- Serum sodium mean (only > 90 
and < 190 included)
                                             2,338                                              2,577 
                                                 154                                                  188 
N/A
N/A
                                             2,492                                              2,765 
...mean (sd)
140.09 (3.01)
140.14 (2.99)
-0.02
139.54 (2.88)
139.92 (2.69)
-0.14
N/A
N/A
#VALUE!
140.06 (3.00)
140.13 (2.97)
-0.02
...median [IQR]
140.00 [138.50, 142.00]
140.00 [139.00, 142.00]
0.00
140.00 [138.00, 141.00]
140.00 [138.00, 142.00]
0.00
N/A
N/A
#VALUE!
140.00 (3.00)
140.00 (2.97)
0.00
...Missing; n (%)
6,612 (73.9%)
6,373 (71.2%)
0.06
11,146 (98.6%)
11,112 (98.3%)
0.02
N/A
N/A
#VALUE!
17,758 (87.7%)
17,485 (86.3%)
0.04
Lab result number- Albumin mean (only >0 and <=10 
included)
                                             2,092                                              2,243 
                                                 112                                                  146 
N/A
N/A
                                             2,204                                              2,389 
...mean (sd)
4.17 (0.32)
4.18 (0.33)
-0.03
4.01 (0.84)
4.12 (0.36)
-0.17
N/A
N/A
#VALUE!
4.16 (0.36)
4.18 (0.33)
-0.06
...median [IQR]
4.20 [4.00, 4.40]
4.20 [4.00, 4.40]
0.00
4.20 [3.90, 4.40]
4.10 [3.90, 4.40]
0.15
N/A
N/A
#VALUE!
4.20 (0.36)
4.19 (0.33)
0.03
...Missing; n (%)
6,858 (76.6%)
6,707 (74.9%)
0.04
11,188 (99.0%)
11,154 (98.7%)
0.03
N/A
N/A
#VALUE!
18,046 (89.1%)
17,861 (88.2%)
0.03
Lab result number- Glucose (fasting or random) mean 
(only 10-1000 included)
                                             2,309                                              2,565 
                                                 153                                                  186 
N/A
N/A
                                             2,462                                              2,751 
...mean (sd)
113.45 (35.98)
113.73 (37.41)
-0.01
126.15 (58.00)
126.78 (41.66)
-0.01
N/A
N/A
#VALUE!
114.24 (37.72)
114.61 (37.72)
-0.01
...median [IQR]
103.00 [93.00, 121.00]
103.00 [93.00, 122.50]
0.00
113.00 [95.00, 135.00]
116.00 [100.00, 142.00]
-0.06
N/A
N/A
#VALUE!
103.62 (37.72)
103.88 (37.72)
-0.01
...Missing; n (%)
6,641 (74.2%)
6,385 (71.3%)
0.07
11,147 (98.6%)
11,114 (98.4%)
0.02
N/A
N/A
#VALUE!
17,788 (87.8%)
17,499 (86.4%)
0.04
Lab result number- Potassium mean (only 1-7 
included)
                                             2,403                                              2,703 
                                                 159                                                  203 
N/A
N/A
                                             2,562                                              2,906 
...mean (sd)
4.37 (0.43)
4.37 (0.46)
0.00
4.36 (0.45)
4.36 (0.43)
0.00
N/A
N/A
#VALUE!
4.37 (0.43)
4.37 (0.46)
0.00
...median [IQR]
4.40 [4.10, 4.60]
4.40 [4.10, 4.60]
0.00
4.30 [4.10, 4.60]
4.37 [4.10, 4.70]
-0.16
N/A
N/A
#VALUE!
4.39 (0.43)
4.40 (0.46)
-0.02
...Missing; n (%)
6,547 (73.2%)
6,247 (69.8%)
0.08
11,141 (98.6%)
11,097 (98.2%)
0.03
N/A
N/A
#VALUE!
17,688 (87.3%)
17,344 (85.6%)
0.05
Comorbidity Scores
CCI (180 days)- ICD9 and ICD10 v2
...mean (sd)
3.47 (1.71)
3.48 (1.74)
-0.01
3.15 (1.62)
3.13 (1.62)
0.01
2.92 (2.09)
2.91 (2.09)
0.00
3.07 (1.93)
3.06 (1.94)
0.01
...median [IQR]
3.00 [2.00, 5.00]
3.00 [2.00, 5.00]
0.00
3.00 [2.00, 4.00]
3.00 [2.00, 4.00]
0.00
3.00 [1.00, 4.00]
3.00 [1.00, 4.00]
0.00
3.00 (1.93)
3.00 (1.94)
0.00
Non-Frailty; n (%)
4,818 (53.8%)
4,943 (55.2%)
-0.03
5,684 (50.3%)
5,645 (50.0%)
0.01
834 (2.7%)
697 (2.2%)
0.03
11,336 (22.1%)
11,285 (22.0%)
0.00
Frailty Score (mean): Empirical Version 365 days, v2
...mean (sd)
0.19 (0.06)
0.19 (0.06)
0.00
0.19 (0.05)
0.19 (0.05)
0.00
17.22 (12.51)
17.23 (12.93)
0.00
10.50 (9.73)
10.51 (10.06)
0.00
...median [IQR]
0.18 [0.15, 0.22]
0.18 [0.15, 0.22]
0.00
0.18 [0.15, 0.21]
0.18 [0.15, 0.21]
0.00
14.67 [8.34, 23.41]
14.52 [8.06, 23.40]
0.01
8.95 (9.73)
8.86 (10.06)
0.01
Appendix B: Rivaroxaban vs Warfarin

Healthcare Utilization
Any hospitalization; n (%)
2,257 (25.2%)
2,314 (25.9%)
-0.02
3,579 (31.7%)
3,582 (31.7%)
0.00
15,976 (51.4%)
15,922 (51.2%)
0.00
21,812 (42.5%)
21,818 (42.5%)
0.00
Any hospitalization within prior 30 days; n (%)
1,520 (17.0%)
1,514 (16.9%)
0.00
2,456 (21.7%)
2,479 (21.9%)
0.00
11,249 (36.2%)
11,049 (35.6%)
0.01
15225 (29.7%)
15042 (29.3%)
0.01
Any hospitalization during prior 31-180 days; n (%)
866 (9.7%)
932 (10.4%)
-0.02
1,279 (11.3%)
1,268 (11.2%)
0.00
6,194 (19.9%)
6,196 (19.9%)
0.00
8339 (16.2%)
8396 (16.4%)
-0.01
Endocrinologist Visit; n (%)
286 (3.2%)
266 (3.0%)
0.01
424 (3.8%)
440 (3.9%)
-0.01
1,662 (5.3%)
1,637 (5.3%)
0.00
2372 (4.6%)
2343 (4.6%)
0.00
Endocrinologist Visit (30 days prior); n (%)
101 (1.1%)
81 (0.9%)
0.02
153 (1.4%)
150 (1.3%)
0.01
557 (1.8%)
540 (1.7%)
0.01
811 (1.6%)
771 (1.5%)
0.01
Endocrinologist Visit (31 to 180 days prior); n (%)
232 (2.6%)
224 (2.5%)
0.01
361 (3.2%)
372 (3.3%)
-0.01
1,406 (4.5%)
1,384 (4.5%)
0.00
1999 (3.9%)
1980 (3.9%)
0.00
Internal medicine/family medicine visits; n (%)
7,789 (87.0%)
7,872 (88.0%)
-0.03
9,294 (82.2%)
9,180 (81.2%)
0.03
27,136 (87.3%)
27,571 (88.7%)
-0.04
44219 (86.2%)
44623 (87.0%)
-0.02
Internal medicine/family medicine visits (30 days 
prior) v2; n (%)
5,509 (61.6%)
5,525 (61.7%)
0.00
6,399 (56.6%)
6,455 (57.1%)
-0.01
20,182 (65.0%)
20,407 (65.7%)
-0.01
32090 (62.5%)
32387 (63.1%)
-0.01
Internal medicine/family medicine visits (31 to 180 
days prior) v2; n (%)
6,784 (75.8%)
6,904 (77.1%)
-0.03
8,254 (73.0%)
8,060 (71.3%)
0.04
23,086 (74.3%)
23,526 (75.7%)
-0.03
38124 (74.3%)
38490 (75.0%)
-0.02
Cardiologist visit; n (%)
6,799 (76.0%)
6,934 (77.5%)
-0.04
6,695 (59.2%)
6,471 (57.3%)
0.04
26,281 (84.6%)
26,471 (85.2%)
-0.02
39775 (77.5%)
39876 (77.7%)
0.00
Number of Cardiologist visits (30 days prior); n (%)
5,531 (61.8%)
5,397 (60.3%)
0.03
4,970 (44.0%)
4,973 (44.0%)
0.00
21,163 (68.1%)
20,800 (66.9%)
0.03
31664 (61.7%)
31170 (60.7%)
0.02
Number of Cardiologist visits (31 to 180 days prior); 
n (%)
4,189 (46.8%)
4,233 (47.3%)
-0.01
4,502 (39.8%)
4,157 (36.8%)
0.06
16,385 (52.7%)
16,402 (52.8%)
0.00
25076 (48.9%)
24792 (48.3%)
0.01
Electrocardiogram v2; n (%)
6,802 (76.0%)
7,027 (78.5%)
-0.06
8,084 (71.5%)
8,613 (76.2%)
-0.11
26,290 (84.6%)
26,741 (86.1%)
-0.04
41176 (80.2%)
42381 (82.6%)
-0.06
Use of glucose test strips; n (%)
109 (1.2%)
124 (1.4%)
-0.02
114 (1.0%)
136 (1.2%)
-0.02
685 (2.2%)
746 (2.4%)
-0.01
908 (1.8%)
1006 (2.0%)
-0.01
Dialysis; n (%)
0 (0.0%)
0 (0.0%)
#DIV/0!
0 (0.0%)
0 (0.0%)
#DIV/0!
**
**
#VALUE!
#VALUE!
#VALUE!
#VALUE!
number of different/distinct medication 
prescriptions
...mean (sd)
9.41 (4.42)
9.45 (4.50)
-0.01
9.77 (4.56)
9.76 (4.56)
0.00
10.93 (4.76)
10.95 (4.85)
0.00
10.41 (4.66)
10.43 (4.73)
0.00
...median [IQR]
9.00 [6.00, 12.00]
9.00 [6.00, 12.00]
0.00
9.00 [7.00, 12.00]
9.00 [7.00, 12.00]
0.00
10.00 [8.00, 14.00]
10.00 [8.00, 14.00]
0.00
5.75 (5.45)
5.75 (5.51)
0.00
Number of Hospitalizations
...mean (sd)
0.29 (0.55)
0.29 (0.54)
0.00
0.35 (0.54)
0.35 (0.55)
0.00
0.65 (0.76)
0.64 (0.76)
0.01
0.52 (0.68)
0.52 (0.68)
0.00
...median [IQR]
0.00 [0.00, 1.00]
0.00 [0.00, 1.00]
0.00
0.00 [0.00, 1.00]
0.00 [0.00, 1.00]
0.00
1.00 [0.00, 1.00]
1.00 [0.00, 1.00]
0.00
0.22 (0.76)
0.22 (0.76)
0.00
Number of hospital days
...mean (sd)
1.34 (3.03)
1.35 (3.73)
0.00
1.66 (3.30)
1.62 (3.81)
0.01
3.67 (5.72)
3.57 (7.18)
0.02
2.82 (4.88)
2.75 (6.07)
0.01
...median [IQR]
0.00 [0.00, 1.00]
0.00 [0.00, 1.00]
0.00
0.00 [0.00, 3.00]
0.00 [0.00, 3.00]
0.00
2.00 [0.00, 5.00]
2.00 [0.00, 5.00]
0.00
0.44 (5.29)
0.44 (6.51)
0.00
Number of Emergency Department (ED) visits v3
...mean (sd)
0.74 (1.32)
0.75 (1.35)
-0.01
0.64 (2.28)
0.63 (2.03)
0.00
1.31 (1.95)
1.31 (1.82)
0.00
1.06 (1.94)
1.06 (1.80)
0.00
...median [IQR]
0.00 [0.00, 1.00]
0.00 [0.00, 1.00]
0.00
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
1.00 [0.00, 2.00]
1.00 [0.00, 2.00]
0.00
0.22 (2.40)
0.22 (2.20)
0.00
Number of Office visits
...mean (sd)
5.46 (4.17)
5.47 (3.88)
0.00
5.89 (4.44)
5.82 (4.17)
0.02
13.22 (13.02)
13.19 (12.41)
0.00
10.25 (10.49)
10.22 (9.98)
0.00
...median [IQR]
5.00 [3.00, 7.00]
5.00 [3.00, 7.00]
0.00
5.00 [3.00, 8.00]
5.00 [3.00, 8.00]
0.00
10.00 [5.00, 17.00]
10.00 [5.00, 17.75]
0.00
4.17 (10.84)
4.17 (10.31)
0.00
Number of Endocrinologist visits
...mean (sd)
0.13 (1.20)
0.11 (0.94)
0.02
0.15 (1.19)
0.16 (1.21)
-0.01
0.26 (1.91)
0.25 (1.78)
0.01
0.21 (1.66)
0.21 (1.55)
0.00
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 (1.82)
0.00 (1.72)
0.00
Number of internal medicine/family medicine visits
...mean (sd)
9.10 (11.33)
9.29 (12.40)
-0.02
7.60 (11.04)
7.50 (10.85)
0.01
9.55 (10.63)
9.49 (10.61)
0.01
9.04 (10.85)
9.02 (10.99)
0.00
...median [IQR]
6.00 [2.00, 12.00]
6.00 [2.00, 12.00]
0.00
4.00 [1.00, 9.00]
4.00 [1.00, 9.00]
0.00
7.00 [2.00, 13.00]
7.00 [3.00, 13.00]
0.00
3.47 (12.83)
3.47 (12.89)
0.00
Number of Cardiologist visits
...mean (sd)
4.73 (5.69)
4.68 (5.48)
0.01
3.10 (4.72)
3.09 (4.65)
0.00
6.14 (7.31)
6.06 (6.74)
0.01
5.22 (6.55)
5.17 (6.12)
0.01
...median [IQR]
3.00 [1.00, 7.00]
3.00 [1.00, 7.00]
0.00
1.00 [0.00, 4.00]
1.00 [0.00, 4.00]
0.00
4.00 [1.00, 8.00]
4.00 [2.00, 8.00]
0.00
1.62 (7.18)
1.62 (6.77)
0.00
Number electrocardiograms received v2
...mean (sd)
2.14 (2.51)
2.15 (2.32)
0.00
1.78 (2.15)
1.77 (1.83)
0.01
2.70 (2.61)
2.69 (2.43)
0.00
2.40 (2.50)
2.39 (2.29)
0.00
...median [IQR]
1.00 [1.00, 3.00]
2.00 [1.00, 3.00]
-0.41
1.00 [0.00, 2.00]
1.00 [1.00, 2.00]
0.00
2.00 [1.00, 4.00]
2.00 [1.00, 4.00]
0.00
0.83 (2.83)
1.01 (2.56)
-0.07
Number of HbA1c tests ordered
...mean (sd)
0.46 (0.73)
0.46 (0.72)
0.00
0.21 (0.54)
0.22 (0.55)
-0.02
0.57 (0.81)
0.57 (0.80)
0.00
0.47 (0.74)
0.47 (0.74)
0.00
...median [IQR]
0.00 [0.00, 1.00]
0.00 [0.00, 1.00]
0.00
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 [0.00, 1.00]
0.00 [0.00, 1.00]
0.00
0.00 (0.82)
0.00 (0.81)
0.00
Number of glucose tests ordered
...mean (sd)
0.21 (2.91)
0.19 (0.82)
0.01
0.13 (0.61)
0.14 (0.89)
-0.01
0.22 (1.26)
0.22 (0.72)
0.00
0.20 (1.59)
0.20 (0.78)
0.00
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 (1.63)
0.00 (0.95)
0.00
Number of lipid tests ordered
...mean (sd)
0.66 (0.84)
0.65 (0.79)
0.01
0.29 (0.74)
0.30 (0.70)
-0.01
0.69 (0.77)
0.69 (0.78)
0.00
0.60 (0.78)
0.60 (0.76)
0.00
...median [IQR]
0.00 [0.00, 1.00]
0.00 [0.00, 1.00]
0.00
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
1.00 [0.00, 1.00]
1.00 [0.00, 1.00]
0.00
0.22 (0.90)
0.22 (0.88)
0.00
Number of creatinine tests ordered
...mean (sd)
0.07 (0.36)
0.07 (0.32)
0.00
0.05 (0.32)
0.05 (0.29)
0.00
0.12 (0.45)
0.11 (0.43)
0.02
0.10 (0.41)
0.09 (0.39)
0.02
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 (0.46)
0.00 (0.43)
0.00
Number of BUN tests ordered
...mean (sd)
0.04 (0.28)
0.04 (0.24)
0.00
0.03 (0.25)
0.03 (0.23)
0.00
0.08 (0.37)
0.07 (0.33)
0.03
0.06 (0.33)
0.06 (0.30)
0.00
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 (0.37)
0.00 (0.33)
0.00
Number of tests for microalbuminuria
...mean (sd)
0.22 (0.66)
0.22 (0.66)
0.00
0.09 (0.43)
0.09 (0.41)
0.00
0.17 (0.50)
0.16 (0.47)
0.02
0.16 (0.52)
0.16 (0.50)
0.00
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 (0.58)
0.00 (0.56)
0.00
Total N distinct ICD9/ICD10 diagnoses at the 3rd 
digit level Copy
...mean (sd)
7.69 (8.86)
7.57 (8.88)
0.01
3.87 (6.60)
3.82 (6.57)
0.01
11.49 (12.00)
11.34 (12.10)
0.01
9.15 (10.51)
9.03 (10.58)
0.01
...median [IQR]
5.00 [0.00, 12.00]
5.00 [0.00, 11.00]
0.00
0.00 [0.00, 5.00]
0.00 [0.00, 5.00]
0.00
8.00 [0.00, 19.00]
8.00 [0.00, 18.00]
0.00
2.63 (11.28)
2.63 (11.34)
0.00
Appendix B: Rivaroxaban vs Warfarin

For PS
Hemorrhagic stroke+Other cerebrovascular 
disease+Cerebrovascular procedure (for PS); n (%)
381 (4.3%)
367 (4.1%)
0.01
377 (3.3%)
377 (3.3%)
0.00
1,762 (5.7%)
1,706 (5.5%)
0.01
2520 (4.9%)
2450 (4.8%)
0.00
Occurrence of creatinine tests ordered (for PS); n (%)
464 (5.2%)
473 (5.3%)
0.00
438 (3.9%)
457 (4.0%)
-0.01
2,763 (8.9%)
2,675 (8.6%)
0.01
3665 (7.1%)
3605 (7.0%)
0.00
Occurrence of BUN tests ordered (for PS); n (%)
267 (3.0%)
278 (3.1%)
-0.01
277 (2.5%)
302 (2.7%)
-0.01
1,749 (5.6%)
1,667 (5.4%)
0.01
2293 (4.5%)
2247 (4.4%)
0.00
Occurrence of chronic renal insufficiency w/o CKD 
(for PS) v2; n (%)
0 (0.0%)
0 (0.0%)
#DIV/0!
0 (0.0%)
0 (0.0%)
#DIV/0!
189 (0.6%)
195 (0.6%)
0.00
189 (0.4%)
195 (0.4%)
0.00
Chronic kidney disease Stage 1-2 (for PS); n (%)
0 (0.0%)
0 (0.0%)
#DIV/0!
0 (0.0%)
0 (0.0%)
#DIV/0!
0
0
#VALUE!
#VALUE!
#VALUE!
#VALUE!
Chronic kidney disease Stage 3-6 (for PS); n (%)
0 (0.0%)
0 (0.0%)
#DIV/0!
0 (0.0%)
0 (0.0%)
#DIV/0!
463 (1.5%)
446 (1.4%)
0.01
463 (0.9%)
446 (0.9%)
0.00
Bladder stones+Kidney stones (for PS); n (%)
84 (0.9%)
97 (1.1%)
-0.02
122 (1.1%)
126 (1.1%)
0.00
487 (1.6%)
494 (1.6%)
0.00
693 (1.4%)
717 (1.4%)
0.00
Diabetes with peripheral circulatory 
disorders+Gangrene+Osteomyelitis(for PS) v3 with 
ICD10 Copy; n (%)
318 (3.6%)
275 (3.1%)
0.03
291 (2.6%)
284 (2.5%)
0.01
1,587 (5.1%)
1,640 (5.3%)
-0.01
2196 (4.3%)
2199 (4.3%)
0.00
Alcohol abuse or dependence+Drug abuse or 
dependence (for PS); n (%)
0 (0.0%)
0 (0.0%)
#DIV/0!
0 (0.0%)
0 (0.0%)
#DIV/0!
95 (0.3%)
84 (0.3%)
0.00
95 (0.2%)
84 (0.2%)
0.00
Diabetes with other ophthalmic 
manifestations+Retinal detachment, vitreous 
hemorrhage, vitrectomy+Retinal laser coagulation 
therapy (for PS); n (%)
42 (0.5%)
46 (0.5%)
0.00
174 (1.5%)
156 (1.4%)
0.01
458 (1.5%)
465 (1.5%)
0.00
674 (1.3%)
667 (1.3%)
0.00
Other atherosclerosis+Cardiac conduction 
disorders+Other CVD (for PS) v2 Copy; n (%)
3,857 (43.1%)
3,825 (42.7%)
0.01
4,510 (39.9%)
4,497 (39.8%)
0.00
14,213 (45.7%)
14,081 (45.3%)
0.01
22580 (44.0%)
22403 (43.7%)
0.01
Previous cardiac procedure (CABG or PTCA or Stent) + 
History of CABG or PTCA (for PS) v3; n (%)
905 (10.1%)
895 (10.0%)
0.00
640 (5.7%)
662 (5.9%)
-0.01
5,079 (16.3%)
4,997 (16.1%)
0.01
6624 (12.9%)
6554 (12.8%)
0.00
Hyperthyroidism + Hypothyroidism + Other disorders 
of thyroid gland (for PS); n (%)
1,955 (21.8%)
1,944 (21.7%)
0.00
1,893 (16.8%)
1,850 (16.4%)
0.01
5,526 (17.8%)
5,502 (17.7%)
0.00
9374 (18.3%)
9296 (18.1%)
0.01
Delirium + Psychosis (for PS); n (%)
279 (3.1%)
261 (2.9%)
0.01
275 (2.4%)
274 (2.4%)
0.00
1,619 (5.2%)
1,599 (5.1%)
0.00
2173 (4.2%)
2134 (4.2%)
0.00
Any use of Meglitinides (for PS); n (%)
23 (0.3%)
20 (0.2%)
0.02
55 (0.5%)
62 (0.5%)
0.00
155 (0.5%)
145 (0.5%)
0.00
233 (0.5%)
227 (0.4%)
0.01
Any use of AGIs (for PS); n (%)
10 (0.1%)
7 (0.1%)
0.00
19 (0.2%)
12 (0.1%)
0.03
42 (0.1%)
42 (0.1%)
0.00
71 (0.1%)
61 (0.1%)
0.00
CKD stage 3-6 + dialysis (for PS); n (%)
0 (0.0%)
0 (0.0%)
#DIV/0!
1 (0.0%)
0 (0.0%)
#DIV/0!
466 (1.5%)
448 (1.4%)
0.01
467 (0.9%)
448 (0.9%)
0.00
Use of thiazide; n (%)
1,119 (12.5%)
1,137 (12.7%)
-0.01
1,374 (12.2%)
1,344 (11.9%)
0.01
4,321 (13.9%)
4,262 (13.7%)
0.01
6814 (13.3%)
6743 (13.1%)
0.01
Use of beta blockers; n (%)
6,279 (70.2%)
6,292 (70.3%)
0.00
8,046 (71.2%)
7,986 (70.7%)
0.01
23,273 (74.9%)
23,216 (74.7%)
0.00
37598 (73.3%)
37494 (73.1%)
0.00
Use of calcium channel blockers; n (%)
3,638 (40.6%)
3,637 (40.6%)
0.00
4,634 (41.0%)
4,646 (41.1%)
0.00
13,887 (44.7%)
13,904 (44.8%)
0.00
22159 (43.2%)
22187 (43.2%)
0.00
All antidiabetic medications except Insulin; n (%)
2,126 (23.8%)
2,148 (24.0%)
0.00
2,739 (24.2%)
2,739 (24.2%)
0.00
9,074 (29.2%)
9,159 (29.5%)
-0.01
13939 (27.2%)
14046 (27.4%)
0.00
DM Medications - Insulin Copy; n (%)
430 (4.8%)
441 (4.9%)
0.00
738 (6.5%)
730 (6.5%)
0.00
2,444 (7.9%)
1,954 (6.3%)
0.06
3612 (7.0%)
3125 (6.1%)
0.04
Use of Low Intensity Statins; n (%)
3,159 (35.3%)
3,116 (34.8%)
0.01
3,741 (33.1%)
3,933 (34.8%)
-0.04
11,556 (37.2%)
11,429 (36.8%)
0.01
18456 (36.0%)
18478 (36.0%)
0.00
Use of High Intensity Statins; n (%)
2,354 (26.3%)
2,408 (26.9%)
-0.01
2,939 (26.0%)
2,814 (24.9%)
0.03
7,959 (25.6%)
8,167 (26.3%)
-0.02
13252 (25.8%)
13389 (26.1%)
-0.01
Malignant hypertension; n (%)
463 (5.2%)
450 (5.0%)
0.01
5,386 (47.7%)
5,398 (47.8%)
0.00
9,493 (30.6%)
9,631 (31.0%)
-0.01
15342 (29.9%)
15479 (30.2%)
-0.01
Cardiovascular stress test; n (%)
38 (0.4%)
40 (0.4%)
0.00
84 (0.7%)
73 (0.6%)
0.01
312 (1.0%)
270 (0.9%)
0.01
434 (0.8%)
383 (0.7%)
0.01
Echocardiogram; n (%)
3,953 (44.2%)
4,195 (46.9%)
-0.05
5,226 (46.2%)
5,820 (51.5%)
-0.11
18,321 (59.0%)
19,059 (61.3%)
-0.05
27500 (53.6%)
29074 (56.7%)
-0.06
Number of BNP tests
...mean (sd)
0.15 (0.52)
0.15 (0.53)
0.00
0.08 (0.40)
0.09 (0.40)
-0.03
0.25 (0.65)
0.27 (0.66)
-0.03
0.20 (0.58)
0.21 (0.59)
0.00
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 (0.63)
0.00 (0.64)
0.00
Number of Cardiac biomarkers tests (tropnin, CK-MBs, Myoglobin, CPK)
...mean (sd)
0.45 (1.43)
0.49 (1.47)
-0.03
0.32 (1.24)
0.39 (1.40)
-0.05
0.36 (0.71)
0.41 (0.73)
-0.07
0.37 (1.00)
0.42 (1.06)
0.00
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 [0.00, 1.00]
0.00 [0.00, 1.00]
0.00
0.00 (1.26)
0.00 (1.37)
0.00
Number of Ambulatory Blood pressure monitoring tests
...mean (sd)
0.00 (0.04)
0.00 (0.04)
0.00
0.00 (0.03)
0.00 (0.04)
0.00
0.00 (0.03)
0.00 (0.04)
0.00
0.00 (0.03)
0.00 (0.04)
0.00
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 (0.04)
0.00 (0.05)
0.00
N of days on antihypertensive medications during baseline
...mean (sd)
139.61 (62.26)
137.95 (63.30)
0.03
139.79 (63.30)
139.00 (63.70)
0.01
147.57 (55.78)
147.35 (55.84)
0.00
144.47 (58.67)
143.87 (58.99)
0.00
...median [IQR]
174.00 [123.00, 181.00]
174.00 [117.00, 181.00]
0.00
176.00 [125.00, 181.00]
175.00 [121.00, 181.00]
0.02
176.00 [144.00, 181.00]
176.00 [144.00, 181.00]
0.00
107.85 (70.61)
107.63 (71.01)
0.00
N of days in database anytime prior
...mean (sd)
2,041.05 (1,371.23)
2,042.84 (1,399.19)
0.00
2,552.38 (1,366.73)
2,530.20 (1,365.03)
0.02
811.15 (547.72)
817.84 (520.25)
-0.01
1409.06 (959.60)
1408.54 (956.85)
0.00
...median [IQR]
1,782.50 [856.75, 
3,039.00]
1,747.50 [822.00, 
3,082.00]
0.0398.50 [1,338.00, 3,690.00]84.00 [1,285.00, 3,667.00]
0.01
634.00 [462.00, 963.00]
649.00 [484.00, 971.00]
-0.03
1022.66 (1280.79)
1016.66 (1278.03)
0.00
Mean Copay for per prescription cost (charges in U.S. $) (180-1 day prior)
...mean (sd)
29.02 (37.48)
29.19 (41.67)
0.00
18.71 (20.72)
18.78 (20.05)
0.00
117.00 (89.10)
118.16 (110.23)
-0.01
80.01 (71.73)
80.76 (88.02)
0.00
...median [IQR]
18.33 [7.69, 36.56]
18.77 [8.00, 35.85]
-0.01
14.04 [6.59, 24.85]
14.11 [6.77, 25.00]
0.00
95.83 [68.28, 137.63]
95.81 [68.80, 135.71]
0.00
27.39 (72.88)
27.48 (88.90)
0.00
...Missing; n (%)
194 (2.2%)
201 (2.2%)
0.00
227 (2.0%)
242 (2.1%)
-0.01
403 (1.3%)
429 (1.4%)
-0.01
824 (1.6%)
872 (1.7%)
-0.01
Colonoscopy; n (%)
235 (2.6%)
238 (2.7%)
-0.01
344 (3.0%)
357 (3.2%)
-0.01
1,007 (3.2%)
974 (3.1%)
0.01
1586 (3.1%)
1569 (3.1%)
0.00
Fecal occult blood (FOB) test; n (%)
274 (3.1%)
282 (3.2%)
-0.01
218 (1.9%)
214 (1.9%)
0.00
787 (2.5%)
777 (2.5%)
0.00
1279 (2.5%)
1273 (2.5%)
0.00
Flu vaccine; n (%)
1,648 (18.4%)
1,646 (18.4%)
0.00
1,355 (12.0%)
1,349 (11.9%)
0.00
10,078 (32.4%)
10,060 (32.4%)
0.00
13081 (25.5%)
13055 (25.4%)
0.00
Mammogram; n (%)
810 (9.1%)
798 (8.9%)
0.01
591 (5.2%)
554 (4.9%)
0.01
2,951 (9.5%)
2,947 (9.5%)
0.00
4352 (8.5%)
4299 (8.4%)
0.00
Pap smear; n (%)
131 (1.5%)
130 (1.5%)
0.00
179 (1.6%)
183 (1.6%)
0.00
515 (1.7%)
531 (1.7%)
0.00
825 (1.6%)
844 (1.6%)
0.00
Appendix B: Rivaroxaban vs Warfarin

Pneumonia vaccine; n (%)
1,307 (14.6%)
1,287 (14.4%)
0.01
660 (5.8%)
672 (5.9%)
0.00
6,181 (19.9%)
6,107 (19.7%)
0.01
8148 (15.9%)
8066 (15.7%)
0.01
PSA test or Prostate exam for DRE; n (%)
1,089 (12.2%)
1,079 (12.1%)
0.00
739 (6.5%)
749 (6.6%)
0.00
3,184 (10.2%)
3,210 (10.3%)
0.00
5012 (9.8%)
5038 (9.8%)
0.00
Bone mineral density; n (%)
309 (3.5%)
299 (3.3%)
0.01
168 (1.5%)
158 (1.4%)
0.01
1,103 (3.6%)
1,076 (3.5%)
0.01
1580 (3.1%)
1533 (3.0%)
0.01
Use of Sympatomimetic agents; n (%)
23 (0.3%)
24 (0.3%)
0.00
50 (0.4%)
51 (0.5%)
-0.01
76 (0.2%)
91 (0.3%)
-0.02
149 (0.3%)
166 (0.3%)
0.00
Use of CNS stimulants; n (%)
23 (0.3%)
25 (0.3%)
0.00
49 (0.4%)
49 (0.4%)
0.00
82 (0.3%)
68 (0.2%)
0.02
154 (0.3%)
142 (0.3%)
0.00
Use of estrogens, progestins, androgens; n (%)
250 (2.8%)
225 (2.5%)
0.02
456 (4.0%)
456 (4.0%)
0.00
856 (2.8%)
904 (2.9%)
-0.01
1562 (3.0%)
1585 (3.1%)
-0.01
Use of Angiogenesis inhibitors; n (%)
1 (0.0%)
1 (0.0%)
#DIV/0!
4 (0.0%)
3 (0.0%)
#DIV/0!
**
12 (0.0%)
#VALUE!
#VALUE!
16 (0.0%)
#VALUE!
Use of Oral Immunosuppressants; n (%)
1 (0.0%)
1 (0.0%)
#DIV/0!
6 (0.1%)
2 (0.0%)
0.04
**
**
#VALUE!
#VALUE!
#VALUE!
#VALUE!
Use of fondaparinux or Bivalirudin; n (%)
4 (0.0%)
1 (0.0%)
#DIV/0!
3 (0.0%)
3 (0.0%)
#DIV/0!
**
11 (0.0%)
#VALUE!
#VALUE!
15 (0.0%)
#VALUE!
Use of other direct thrombin inhibitors (lepirudin, des
0 (0.0%)
0 (0.0%)
#DIV/0!
0 (0.0%)
0 (0.0%)
#DIV/0!
0 (0.0%)
0 (0.0%)
#DIV/0!
0 (0.0%)
0 (0.0%)
#DIV/0!
Use of Ticagrelor ON CED; n (%)
10 (0.1%)
14 (0.2%)
-0.03
21 (0.2%)
13 (0.1%)
0.03
12 (0.0%)
15 (0.0%)
#DIV/0!
43 (0.1%)
42 (0.1%)
0.00
Use of Ticagrelor; n (%)
22 (0.2%)
26 (0.3%)
-0.02
24 (0.2%)
18 (0.2%)
0.00
110 (0.4%)
101 (0.3%)
0.02
156 (0.3%)
145 (0.3%)
0.00
Number of D-dimer tests
...mean (sd)
0.03 (0.21)
0.03 (0.19)
0.00
0.02 (0.16)
0.02 (0.17)
0.00
0.05 (0.23)
0.05 (0.23)
0.00
0.04 (0.21)
0.04 (0.21)
0.00
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 (0.23)
0.00 (0.24)
0.00
Numbe of CRP, high-sensitivity CRP tests
...mean (sd)
0.06 (0.35)
0.06 (0.30)
0.00
0.03 (0.22)
0.03 (0.24)
0.00
0.09 (0.41)
0.09 (0.45)
0.00
0.07 (0.37)
0.07 (0.39)
0.00
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 (0.39)
0.00 (0.42)
0.00
Number of PT or aPTTt tests
...mean (sd)
0.52 (1.32)
0.48 (1.43)
0.03
0.39 (1.18)
0.37 (1.20)
0.02
0.49 (1.24)
0.48 (1.25)
0.01
0.47 (1.24)
0.46 (1.27)
0.00
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 [0.00, 1.00]
0.00 [0.00, 1.00]
0.00
0.00 (1.44)
0.00 (1.47)
0.00
Number of Bleeding time tests
...mean (sd)
0.00 (0.00)
0.00 (0.00)
#DIV/0!
0.00 (0.00)
0.00 (0.00)
#DIV/0!
0.00 (0.01)
0.00 (0.01)
0.00
0.00 (0.01)
0.00 (0.01)
0.00
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
#DIV/0!
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
#DIV/0!
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 (0.01)
0.00 (0.01)
0.00
HAS-BLED Score (ICD-9 and ICD-10), 180 days
...mean (sd)
3.41 (0.76)
3.40 (0.76)
0.01
3.29 (0.77)
3.29 (0.76)
0.00
3.56 (0.74)
3.55 (0.73)
0.01
3.47 (0.75)
3.47 (0.74)
0.00
...median [IQR]
3.00 [3.00, 4.00]
3.00 [3.00, 4.00]
0.00
3.00 [3.00, 4.00]
3.00 [3.00, 4.00]
0.00
3.00 [3.00, 4.00]
3.00 [3.00, 4.00]
0.00
1.84 (0.89)
1.84 (0.88)
0.00
N of Generic name drugs
...mean (sd)
19.22 (14.62)
19.38 (16.57)
-0.01
14.89 (10.15)
14.82 (11.14)
0.01
20.43 (14.14)
20.47 (15.60)
0.00
19.00 (13.45)
19.04 (14.92)
0.00
...median [IQR]
16.00 [10.00, 24.00]
15.00 [9.00, 25.00]
0.06
13.00 [8.00, 19.00]
12.00 [7.00, 19.00]
0.09
17.00 [11.00, 26.00]
17.00 [10.00, 26.00]
0.00
9.40 (14.86)
9.00 (16.44)
0.00
N of Brand name drugs
...mean (sd)
4.15 (6.18)
4.22 (4.32)
-0.01
4.70 (5.32)
4.76 (4.21)
-0.01
4.78 (6.13)
4.92 (5.14)
-0.02
4.65 (5.97)
4.76 (4.81)
0.00
...median [IQR]
2.00 [0.00, 6.00]
3.00 [1.00, 6.00]
-0.19
3.00 [1.00, 7.00]
4.00 [2.00, 7.00]
-0.21
3.00 [1.00, 7.00]
3.00 [1.00, 7.00]
0.00
1.67 (6.82)
2.06 (5.48)
0.00
Use of clopidogrel ; n (%)
1,027 (11.5%)
1,017 (11.4%)
0.00
1,382 (12.2%)
1,356 (12.0%)
0.01
4,482 (14.4%)
4,428 (14.3%)
0.00
6891 (13.4%)
6801 (13.3%)
0.00
Systemic embolism; n (%)
70 (0.8%)
67 (0.7%)
0.01
87 (0.8%)
86 (0.8%)
0.00
324 (1.0%)
306 (1.0%)
0.00
481 (0.9%)
459 (0.9%)
0.00
DVT; n (%)
23 (0.3%)
29 (0.3%)
0.00
25 (0.2%)
24 (0.2%)
0.00
562 (1.8%)
559 (1.8%)
0.00
610 (1.2%)
612 (1.2%)
0.00
PE; n (%)
0 (0.0%)
0 (0.0%)
#DIV/0!
0 (0.0%)
0 (0.0%)
#DIV/0!
144 (0.5%)
141 (0.5%)
0.00
144 (0.3%)
141 (0.3%)
0.00
Diabetes: 1 inpatient or 2 outpatient claims within 18
3,058 (34.2%)
3,112 (34.8%)
-0.01
3,583 (31.7%)
3,591 (31.8%)
0.00
13,784 (44.4%)
13,855 (44.6%)
0.00
20425 (39.8%)
20558 (40.1%)
-0.01
Intracranial or retroperitoneal hemorrhage: 1 inpatien
13 (0.1%)
12 (0.1%)
0.00
15 (0.1%)
17 (0.2%)
-0.03
101 (0.3%)
99 (0.3%)
0.00
129 (0.3%)
128 (0.2%)
0.02
Peptic Ulcer Disease; n (%)
1,514 (16.9%)
1,506 (16.8%)
0.00
1,294 (11.5%)
1,278 (11.3%)
0.01
7,115 (22.9%)
7,038 (22.7%)
0.00
9923 (19.3%)
9822 (19.1%)
0.01
Upper GI bleed; n (%)
0 (0.0%)
0 (0.0%)
#DIV/0!
0 (0.0%)
0 (0.0%)
#DIV/0!
22 (0.1%)
26 (0.1%)
0.00
22 (0.0%)
26 (0.1%)
-0.04
Lower/ unspecified GI bleed; n (%)
0 (0.0%)
0 (0.0%)
#DIV/0!
0 (0.0%)
0 (0.0%)
#DIV/0!
395 (1.3%)
385 (1.2%)
0.01
395 (0.8%)
385 (0.8%)
0.00
Urogenital bleed; n (%)
0 (0.0%)
1 (0.0%)
#DIV/0!
0 (0.0%)
0 (0.0%)
#DIV/0!
527 (1.7%)
533 (1.7%)
0.00
527 (1.0%)
534 (1.0%)
0.00
Other bleeds; n (%)
1 (0.0%)
1 (0.0%)
#DIV/0!
0 (0.0%)
0 (0.0%)
#DIV/0!
328 (1.1%)
314 (1.0%)
0.01
329 (0.6%)
315 (0.6%)
0.00
Prior cancer; n (%)
1,130 (12.6%)
1,119 (12.5%)
0.00
1,106 (9.8%)
1,063 (9.4%)
0.01
4,090 (13.2%)
4,060 (13.1%)
0.00
6326 (12.3%)
6242 (12.2%)
0.00
Aspirin; n (%)
68 (0.8%)
71 (0.8%)
0.00
186 (1.6%)
184 (1.6%)
0.00
201 (0.6%)
201 (0.6%)
0.00
455 (0.9%)
456 (0.9%)
0.00
Aspirin/dipyridamole; n (%)
37 (0.4%)
32 (0.4%)
0.00
79 (0.7%)
75 (0.7%)
0.00
180 (0.6%)
185 (0.6%)
0.00
296 (0.6%)
292 (0.6%)
0.00
Other antiplatelet agents; n (%)
48 (0.5%)
46 (0.5%)
0.00
62 (0.5%)
71 (0.6%)
-0.01
215 (0.7%)
224 (0.7%)
0.00
325 (0.6%)
341 (0.7%)
-0.01
PGP inhibitors; n (%)
3,868 (43.2%)
3,887 (43.4%)
0.00
5,184 (45.9%)
5,203 (46.0%)
0.00
15,745 (50.7%)
15,746 (50.7%)
0.00
24797 (48.3%)
24836 (48.4%)
0.00
Other gastroprotective agents; n (%)
81 (0.9%)
86 (1.0%)
-0.01
125 (1.1%)
122 (1.1%)
0.00
461 (1.5%)
459 (1.5%)
0.00
667 (1.3%)
667 (1.3%)
0.00
Number of lipid tests ordered
...mean (sd)
0.66 (0.84)
0.65 (0.79)
0.01
0.29 (0.74)
0.30 (0.70)
-0.01
0.72 (0.84)
0.72 (0.84)
0.00
0.61 (0.82)
0.62 (0.80)
0.00
...median [IQR]
0.00 [0.00, 1.00]
0.00 [0.00, 1.00]
0.00
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
1.00 [0.00, 1.00]
1.00 [0.00, 1.00]
0.00
0.22 (0.94)
0.22 (0.91)
0.00
Proton pump inhibitor; n (%)
1,891 (21.1%)
1,928 (21.5%)
-0.01
2,511 (22.2%)
2,460 (21.8%)
0.01
8,637 (27.8%)
8,657 (27.9%)
0.00
13039 (25.4%)
13045 (25.4%)
0.00
H2 receptor antagonist; n (%)
406 (4.5%)
402 (4.5%)
0.00
429 (3.8%)
425 (3.8%)
0.00
2,128 (6.8%)
2,152 (6.9%)
0.00
2963 (5.8%)
2979 (5.8%)
0.00
Vitamin K therapy; n (%)
4 (0.0%)
3 (0.0%)
#DIV/0!
5 (0.0%)
4 (0.0%)
#DIV/0!
**
**
#VALUE!
#VALUE!
#VALUE!
#VALUE!
Number of neurologist visits
...mean (sd)
0.32 (1.39)
0.31 (1.36)
0.01
0.25 (1.17)
0.25 (1.37)
0.00
0.55 (2.12)
0.54 (2.05)
0.00
0.44 (1.83)
0.44 (1.81)
0.00
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 (1.97)
0.00 (2.00)
0.00
Number of INR (prothrombin) tests ordered
...mean (sd)
0.37 (1.01)
0.33 (1.10)
0.04
0.28 (0.89)
0.26 (0.93)
0.02
0.47 (1.19)
0.46 (1.21)
0.01
0.41 (1.10)
0.39 (1.13)
0.00
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 [0.00, 1.00]
0.00 [0.00, 1.00]
0.00
0.00 (1.23)
0.00 (1.27)
0.00
Treating prescriber - Cardiologist; n (%)
5,550 (62.0%)
5,429 (60.7%)
0.03
5,961 (52.8%)
5,881 (52.0%)
0.02
21,163 (68.1%)
20,800 (66.9%)
0.03
32674 (63.7%)
32110 (62.6%)
0.02
Treating prescriber - Primary Care Physician; n (%)
5,841 (65.3%)
5,877 (65.7%)
-0.01
3,792 (33.6%)
3,789 (33.5%)
0.00
9,315 (30.0%)
9,328 (30.0%)
0.00
18948 (36.9%)
18994 (37.0%)
0.00
Treating prescriber - Other; n (%)
7,646 (85.4%)
7,591 (84.8%)
0.02
9,048 (80.1%)
8,979 (79.5%)
0.01
27,784 (89.4%)
27,618 (88.9%)
0.02
44478 (86.7%)
44188 (86.1%)
0.02
Appendix B: Rivaroxaban vs Warfarin

Alpha blockers; n (%)
1,102 (12.3%)
1,081 (12.1%)
0.01
1,377 (12.2%)
1,405 (12.4%)
-0.01
3,766 (12.1%)
3,807 (12.3%)
-0.01
6245 (12.2%)
6293 (12.3%)
0.00
CHADS2 score, 180 days, V
...mean (sd)
2.10 (1.19)
2.11 (1.19)
-0.01
2.19 (1.18)
2.20 (1.19)
-0.01
3.73 (1.65)
3.73 (1.64)
0.00
3.11 (1.48)
3.11 (1.48)
0.00
...median [IQR]
2.00 [1.00, 3.00]
2.00 [1.00, 3.00]
0.00
2.00 [1.00, 3.00]
2.00 [1.00, 3.00]
0.00
3.00 [3.00, 5.00]
3.00 [3.00, 5.00]
0.00
1.45 (1.65)
1.45 (1.65)
0.00
Use of Prasugrel; n (%)
25 (0.3%)
24 (0.3%)
0.00
40 (0.4%)
30 (0.3%)
0.02
**
**
#VALUE!
#VALUE!
#VALUE!
#VALUE!
Use of Loop Diuretics+other diuretics+other hypertens
3,023 (33.8%)
3,035 (33.9%)
0.00
3,753 (33.2%)
3,790 (33.5%)
-0.01
13,931 (44.8%)
14,150 (45.5%)
-0.01
20707 (40.4%)
20975 (40.9%)
-0.01
Commercial vs Medicare Advantage- Business Type Code - CORRECT ONE - OPTUM
0
0
...Commercial; n (%)
1461 (16.3%)
1463 (16.3%)
0.00
9,248 (81.8%)
9,258 (81.9%)
0.00
-
-
#VALUE!
10,709 (52.9%)
10,721 (52.9%)
0.00
...Medicare Advantage; n (%)
7,489 (83.7%)
7487 (83.7%)
0.00
2,052 (18.2%)
2,042 (18.1%)
0.00
-
-
#VALUE!
9,541 (47.1%)
9,529 (47.1%)
0.00
Commercial vs Medicare Advantage- Business Type Code
...COM = COMMERCIAL; n (%)
1,461 (16.3%)
1,463 (16.3%)
0.00
-
-
#VALUE!
-
-
#VALUE!
1,461 (16.3%)
1,463 (16.3%)
0.00
...MCR = MEDICARE; n (%)
7,489 (83.7%)
7,487 (83.7%)
0.00
-
-
#VALUE!
-
-
#VALUE!
7,489 (83.7%)
7,487 (83.7%)
0.00
...MCD = MEDICAID; n (%)
0 (0.0%)
0 (0.0%)
#DIV/0!
-
-
#VALUE!
-
-
#VALUE!
0 (0.0%)
0 (0.0%)
#DIV/0!
...NONE = NO BUSINESS LINE CODE (added in 2015); n (
0 (0.0%)
0 (0.0%)
#DIV/0!
-
-
#VALUE!
-
-
#VALUE!
0 (0.0%)
0 (0.0%)
#DIV/0!
...UNK = UNKNOWN (added in 2015); n (%)
0 (0.0%)
0 (0.0%)
#DIV/0!
-
-
#VALUE!
-
-
#VALUE!
0 (0.0%)
0 (0.0%)
#DIV/0!
Commercial vs Medicare Advantage- Data Type
-
-
0
0
-
-
...1 - Fee For Service; n (%)
-
-
1,803 (16.0%)
1,817 (16.1%)
-
-
1,803 (16.0%)
1,817 (16.1%)
0.00
...2 - Encounter; n (%)
-
-
249 (2.2%)
225 (2.0%)
-
-
249 (2.2%)
225 (2.0%)
0.00
...3 - Medicare; n (%)
-
-
8,539 (75.6%)
8,523 (75.4%)
-
-
8,539 (75.6%)
8,523 (75.4%)
0.00
...4 - Medicare Encounter; n (%)
-
-
709 (6.3%)
735 (6.5%)
-
-
709 (6.3%)
735 (6.5%)
0.00
Metropolitan Statistical Area - Urban (any MSA) vs Rural (non-MSA)
0
0
0.00
...Urban; n (%)
-
-
8,353 (73.9%)
8,402 (74.4%)
-
-
8,353 (73.9%)
8,402 (74.4%)
0.00
...Rural; n (%)
-
-
295 (2.6%)
286 (2.5%)
-
-
295 (2.6%)
286 (2.5%)
0.00
...Unknown/Missing; n (%)
-
-
2,652 (23.5%)
2,612 (23.1%)
-
-
2,652 (23.5%)
2,612 (23.1%)
0.00
Due to CMS cell suppression policy, all values less than 11 are denoted 
with **
Appendix B: Rivaroxaban vs Warfarin