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XARELTO® (rivaroxaban)

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Real-World Data of XARELTO vs Apixaban in Non-Valvular Atrial Fibrillation

Last Updated: 07/28/2025

SummarY

  • Data from the United States Food and Drug Administration (FDA) Sentinel database (Section: FDA Sentinel Reports) has evaluated the incidence of major bleeding events in groups of patients stratified by age (<65 years and ≥65 years) receiving various direct oral anticoagulants (DOACs; XARELTO, apixaban, dabigatran and edoxaban).1,2
    • For patients aged <65 years:
      • In a comparison of XARELTO vs apixaban, the hazard ratio (HR) was 1.63 (95% confidence interval [CI], 0.99-2.70 by inverse probability of treatment weighted pairwise comparison [IPTW]) for intracranial hemorrhage (ICH), 1.91 (95% CI, 1.56-2.34 by IPTW) for major gastrointestinal (GI) bleeding, and 1.92 (95% CI, 1.54-2.39 by IPTW) for major extracranial bleeding (MEB).1
    • For patients aged ≥65 years:
      • In a comparison of XARELTO vs apixaban, the HR was 1.28 (95% CI, 0.99-1.67 by propensity score matching [PSM]) and 1.23 (95% CI, 0.96-1.58 by IPTW) for ICH, 2.32 (95% CI, 2.07-2.59 by PSM) and 2.35 (95% CI, 2.11-2.61 by IPTW) for major GI bleeding, and 2.29 (95% CI, 2.06-2.55 by PSM) and 2.33 (95% CI, 2.11-2.58 by IPTW) for MEB.2
  • Currently, no randomized, controlled, head-to-head trials evaluating the use of DOACs in nonvalvular atrial fibrillation (NVAF) have been reported in the literature. Data from real-world studies is included in this response and summarized below (Section: Real-World Evidence)
  • Additional studies conducted in the United States (US) have been included in the References section for your review.3-5
  • Additional studies conducted outside of the US have been included in the References section for your review.6-10
  • Systematic review and meta-analyses have been included in the References section for your review.11,12

FDA SEntinel reports

  • As part of its pharmacovigilance Sentinel Initiative, the FDA conducts retrospective analyses of safety data collected from electronic health records of patients receiving FDA-regulated drugs. The results of these analyses are published in Sentinel reports.13
  • Sentinel reports containing data on major bleeding events in patients with NVAF receiving XARELTO are summarized below in Table: Sentinel Bleeding Rates in Patients With NVAF Aged <65 Years and ≥65 Years
    • Each retrospective cohort study evaluated new users of standard-dose apixaban 5 mg twice daily (BID), dabigatran 150 mg BID, and XARELTO 20 mg every day (QD) with a diagnosis of NVAF in the preceding 183 days from the Medicare database between 10/19/2020-2/28/22. Patients with kidney replacement, DVT, PE, joint replacement, mitral stenosis, valve replacement or repair, or receiving dialysis were excluded.1,2

Sentinel Bleeding Rates in Patients With NVAF Aged <65 Years and ≥65 Years
Patients Aged <65 Years
Study Design
Results
Cohorts
HR (95% CI)
MEB
GI Bleeding
ICH
Bradley et al (2024)1
XARELTO vs apixaban by IPTW
(n=57,932 vs 96,057)
1.92
(1.54-2.39)
1.91
(1.56-2.34)
1.63
(0.99-2.70)a
Patients Aged ≥65 Years
Bradley et al (2022)2
XARELTO vs apixaban by IPTW
(n=111,814 vs 77,234)
2.33
(2.11-2.58)
2.35
(2.11-2.61)
1.23
(0.96-1.58)a
XARELTO vs apixaban by PSM
(n=75,889)
2.29
(2.06-2.55)
2.32
(2.07-2.59)
1.28
(0.99-1.67)a
Abbreviations: CI, confidence interval; GI, gastrointestinal; HR, hazard ratio; ICH, intracranial hemorrhage; IPTW, inverse probability of treatment weighted pairwise comparisons; MEB, major extracranial bleeding; NVAF, nonvalvular atrial fibrillation; PSM, propensity score matching.
aStatistical significance was not achieved.

Real-World Evidence

There are no head-to-head randomized clinical trials that directly compare the safety and efficacy of XARELTO and apixaban for the reduction in risk of stroke and systemic embolism (SE) in patients with NVAF. Some limitations of real-world data studies include: 

  • Residual confounding due to unmeasured factors that are either not available in the database or were not accounted for in the statistical analysis.
  • Potential misclassification of exposure and outcomes.
  • Composition of the population may limit the generalizability of the findings.

The following information is primarily comprised of US population studies of real-world evidence data pertaining to XARELTO vs apixaban in NVAF. Summaries of studies conducted outside the US are incorporated for your professional review. Please note, studies conducted outside the US may differ in the patient population(s) and/or medication dose(s) evaluated.


US Population
Study
Patients
Outcomes
Atreja et al (2025)14 
Retrospective, observational study using Fee-for-Service Medicare claims data from the US Centers for Medicare & Medicaid Services database between January 1, 2013, and December 31, 2019
Used IPTW to adjust for baseline differences.
Study Population
Adult patients with a prescription for an oral anticoagulant on or after the first AF diagnosis
Key Demographics
After IPTW weighting,
  • XARELTO
    • Age (mean): 77.84 years
    • 48.76% were male
  • Apixaban
    • Age (mean): 77.71 years
    • 47.76% were male

Study Groups (post PSM)
  • XARELTO (n=267,991)
  • Apixaban (n=486,257)
Apixaban vs XARELTO
HR (95% CI)
P Value
Primary outcomes: stroke/SE (efficacy) and MB (safety)
Stroke/SE
0.88 (0.84-0.92)
<0.0001
   IS
0.93 (0.88-0.97)
0.0012
   Hemorrhagic stroke
0.76 (0.69-0.83)
<0.0001
   SE
0.65 (0.52-0.79)
<0.0001
MB
0.60 (0.58-0.61)
<0.0001
   GI bleeding
0.52 (0.51-0.54)
<0.0001
   ICH
0.86 (0.81-0.92)
<0.0001
   Other
0.68 (0.63-0.72)
<0.0001
Dawwas et al (2025)15 
Retrospective cohort study using healthcare claims data from MarketScan IBM from January 1, 2014, to
December 31, 2021.
Used 1:1 PSM
Study Population
Patients aged ≥65 years with a diagnosis of AF and who were anticoagulant naïve.
Key Demographics
  • XARELTO
    • Age (mean): 77 years
    • 54.2% were male
  • Apixaban
    • Age (mean): 77 years
    • 54% were male

Study Groups (post PSM)
  • XARELTO (n=31,896)
  • Apixaban (n=31,896)

Median follow-up was 219 days in the XARELTO cohort vs 219 days in the apixaban cohort in the matched sample.
XARELTO
Apixaban
Marginal HRa
(95% CI)
Primary outcomes: stroke/SE (efficacy) and GI/ICH bleeding (safety)
Stroke/SE, n
509
391
1.23
(1.08-1.40)
   PY of follow-up
31,216
28,921
   IR per 1000 PY
16.3
13.5
Bleeding events, n
1,129
670
1.60
(1.45-1.76)
   PY of follow-up
30,991
28,892
   IR per 1000 PY
36.4
23.2
Quinlan et al (2025)16 
Retrospective cohort study using the US Medicare Fee-for-Service database between January 1, 2013, and December 31, 2020.
Used PSM
Study Population
Patients aged 50 years or older with a diagnosis of NVAF or flutter.
Key Demographics
  • XARELTO
    • Age (mean): 66.5 years
    • 79.4% were male
  • Apixaban
    • Age (mean): 66.5 years
    • 79.4% were male

Study Groups
  • XARELTO (n=629)
  • Apixaban (n=1547)

Median follow-up was 365 days.
Outcome
Apixaban
XARELTO
HR
(95% CI)
No. of Events
(Incidence per 1000 PY)
Primary outcome: hospitalization for MB
MB
30 (20.05)
21 (42.94)
2.15
(1.18-3.94)
Secondary outcomes
Major GI bleeding
15 (8.57)
14 (28.49)
3.38
(1.57-7.25)
IS
15 (9.69)
<11 (NAb)
NAb
Composite (MB to IS)
42 (27.95)
22 (45.70)
1.64
(0.95-2.86)
Death (all cause)
208 (140.25)
71 (131.75)
0.94
(0.71-1.26)
Lip et al (2024)17 Retrospective study using 4 US commercial claims databases (IQVIA LifeLink PharMetrics Plus, Truven MarketScan Commercial Claims and Encounters, OptumInsight, and the Humana Database) between January 1, 2012 and June 30, 2019.
Used 1:1 PSM
Study Population
Adult patients with NVAF who switched from warfarin to DOACs
Key Demographics
  • Mean age was 72.2 in both apixaban and XARELTO cohorts
  • 56.8% were men in both the cohorts

Study Groups (post PSM)
  • Apixaban (N=12,165)
  • XARELTO (N=12,165)
Apixaban
XARELTO (ref)
HR
(95% CI)
P Value
Primary effectiveness outcome
   Stroke/SE
1.80
2.03
0.88
(0.73-1.07)
0.19
   Ischemic
1.50
1.69
0.89
(0.72-1.09)
0.25
   Hemorrhagic
0.21
0.27
0.81
(0.47-1.38)
0.43
   SE
0.13
0.11
1.12
(0.53-2.38)
0.77
Primary safety outcome
   MB
3.04
5.03
0.60
(0.52-0.68)
<0.0001
   GI
1.62
3.07
0.52
(0.43-0.62)
<0.0001
   ICH
0.55
0.56
0.98
(0.69-1.38)
0.88
   Other bleeding
0.99
1.65
0.59
(0.46-0.74)
<0.0001
Mahesri et al (2024)18
New-user comparative cohort study designed to replicate the COBRA-AF and COBRA-VTE studies
Study Population
Patients with AF or VTE receiving XARELTO or apixaban
Study Groups
  • COBRRA-AF (N=177,866 PSM pairs)
  • COBRRA-VTE (N=14,202 PSM pairs)
Primary outcomes [composite MB and clinically relevant non-MB]
  • COBRRA-AF
    • In patients with AF, the risk of major and clinically relevant non-MB was decreased 31% with apixaban compared to XARELTO (HR, 0.69; 95% CI, 0.66-0.71).
Lawal et al (2023)19 Retrospective cohort study using data from the Optum Clinformatics Data Mart Database between January 2011 and December 2017
Study Population
Patients with AF and chronic liver disease receiving a DOAC or warfarin
Key Demographics
Median age: 72 (64-79) years
Study Groups
  • XARELTO (N=2211)
  • Apixaban (N=2721)
  • Warfarin (N=4421)

Note: Patients who received dabigatran and edoxaban were excluded from the analyses due to their small sample sizes.
No. of Events
(IR/100 PY)c
HR
(95% CI)c
Primary outcomes (hospitalization for IS/SE and MB)
XARELTO (N=2211)
Apixaban (N=2721)
IS/SE
34 (2.6)
21 (1.3)
1.73 (0.91-3.29)
MB
119 (10.3)
98 (6.2)
1.59 (1.18-2.14)
  • The risk of hospitalization for IS/SE was not significantly different with XARELTO vs warfarin (HR, 0.76; 95% CI, 0.47-1.21), but was significantly lower with apixaban vs warfarin (HR, 0.40; 95% CI, 0.19-0.82).
  • The risk of hospitalization for MB was lower with XARELTO vs warfarin (HR, 0.79; 95% CI, 0.62-1.0) and apixaban vs warfarin (HR, 0.60; 95% CI, 0.46-0.78).
Lip et al (2022)20 Retrospective, observational data analysis using 5 insurance databases (Fee-for-Service Medicare data from the US Centers for Medicare & Medicaid Services, the IBM Watson Health MarketScan Commercial Claims and Encounter, the IQVIA PharMetrics Plus™ Database, the Optum Clinformatics™ Data Mart, and the Humana Research Database) between January 1, 2013, and June 30, 2019.
Used 1:1 PSM to adjust for baseline differences.
Study Population
Adult patients with NVAF and a history of bleeding events.
Key Demographics
  • Mean age range: 77-78 years

Study Groups (post PSM)
  • NOAC vs warfarin
    • 37,405 XARELTO-warfarin
    • 50,435 apixaban-warfarin
    • 12,436 dabigatran-warfarin
  • NOAC vs NOAC
    • 35,376 apixaban-XARELTO
    • 12,275 apixaban-dabigatran
    • 12,297 dabigatran-XARELTO

Edoxaban patients were excluded due to the small sample size. Results for apixaban vs dabigatran are not included here but they are presented in the publication.
Comparatord
Refd
No. of Events
(Incidence per 100 PY)
Primary outcomes: stroke/SE (efficacy) and MB (safety)
Apixaban vs XARELTO (ref)
   Stroke/SE
2.24
2.63
HR 0.85 (95% CI 0.76-0.96); P=0.0077
   MB
8.87
13.54
HR 0.64 (95% CI 0.61-0.68); P<0.0001
Dabigatran vs XARELTO (ref)
   Stroke/SE
2.55
2.45
HR 1.04 (95% CI 0.87-1.25); P=0.6749
   MB
10.87
13.27
HR 0.84 (95% CI 0.77-0.92); P<0.0001
  • The unadjusted IRs per 100 PY of stroke/SE, including IS, hemorrhagic stroke, and SE, for XARELTO, apixaban, dabigatran, and warfarin were 2.5, 2.7, 2.6, and 2.9, respectively.
  • Similarly, the unadjusted IRs per 100 PY of MB, including GI bleeding, ICH, and MB at other key sites, for XARELTO, apixaban, dabigatran, and warfarin were 13.4, 9.4, 10.9, and 13.6, respectively.
Ray et al (2021)21 Retrospective cohort analysis of US Medicare program and claims from medical care services from January 1, 2013, and November 30, 2018.
Used IPTW to adjust for baseline differences.
Study Population
Patients aged ≥65 years with a diagnosis of AF or flutter in the past 90 days
Key Demographics
  • XARELTO
    • Age (mean): 77
    • CHA2DS2-VASc (mean): 4.3
  • Apixaban
    • Age (mean): 77
    • CHA2DS2-VASc (mean): 4.3

Study Groups
  • XARELTO (N=227,572)
  • apixaban (N=353,879)

Median follow-up was 174 days (176 for apixaban and 171 days for XARELTO).
Primary outcomes: composite of major ischemic or hemorrhagic events (IS, SE, hemorrhagic stroke, other intracranial bleeding, and fatal extracranial bleeding)
  • Composite of major ischemic/hemorrhagic event HR (95% CI): XARELTO vs apixaban 1.18 (1.12-1.24)
  • IS HR (95% CI): XARELTO vs apixaban 1.12 (1.05-1.21)
  • Hemorrhagic Stroke HR (95% CI): XARELTO vs apixaban 1.48 (1.30-1.70)
  • Other ICH HR (95% CI): XARELTO vs apixaban 1.09 (0.98-1.22)
  • Fatal extracranial bleeding HR (95% CI): XARELTO vs apixaban 1.41 (1.18-1.70)

Secondary outcomes: nonfatal extracranial bleeding and total mortality
  • Nonfatal extracranial bleeding HR (95% CI): XARELTO vs apixaban 2.07 (1.99-2.15)
  • GI bleeding HR (95% CI): XARELTO vs apixaban 2.09 (2.01-2.18)
  • Total mortality HR (95% CI): XARELTO vs apixaban 1.06 (1.02-1.09)
Fralick et al (2020)22
Retrospective, new-user, active-comparator analysis using nationwide US commercial insurance claims database Optum Clinformatics between December 28, 2012 and January 1, 2019.
Used 1:1 PSM to adjust for baseline differences
Study population
Patient’s age ≥18 years with AF/flutter and filled new prescription for XARELTO or apixaban
Key Demographics
  • XARELTO
    • Age (mean): 69 years
    • CHADS2 score ≥2, 44.5%
  • Apixaban
    • Age (mean): 69 years
    • CHADS2 score ≥2, 44.9%

Study Groups (post PSM)
  • XARELTO (N=39,351)
  • Apixaban (N=39,351)

Mean follow-up was 291 days for
XARELTO and 288 days for apixaban
  • Effectiveness: composite of IS or SE (also as separate endpoints)
  • Safety: composite of GI bleeding or ICH (also as separate endpoints), other bleeding
  • After PSM, IR of IS or SE was 6.6/1000 PY for apixaban-treated patients and 8.0/1000 PY for XARELTO-treated patients (HR, 0.82; 95% CI, 0.68-0.98; rate difference, 1.4 fewer events/1000 PY [CI, 0.0-2.7]).
  • Apixaban-treated patients experienced a lower rate of GI bleeding or ICH vs XARELTOtreated patients (12.9/1000 PY vs 21.9/1000 PY, respectively; HR, 0.58; CI, 0.52-0.66; rate difference: 9.0 fewer events/1000 PY [CI, 6.9-11.1]).
Lip et al (2018)23 Retrospective, observational study using
4 US commercial claims databases (the Truven MarketScan Commercial Claims and Encounter and Medicare Supplemental and Coordination of Benefits Database, the IMS PharMetrics Plus Database, the Optum
Clinformatics Data Mart, and the Humana Research Database) and Centers for Medicare and Medicaid Services Medicare data between January 1, 2013 to September 30 2015
Used 1:1 PSM to adjust for baseline differences
(Additional sub-analyses of this study have been conducted and are included in the reference section.24-31)
Study Population
Patients with NVAF newly initiating apixaban, dabigatran, XARELTO, or warfarin
Key Demographics
  • Mean age range in all groups: 72.8-76.1 years
  • 51.3%-57.4% in all groups were men

Study Groups (post PSM)
  • NOAC vs warfarin
    • 100,977 apixaban-warfarin
    • 36,990 dabigatran-warfarin
    • 125,068 XARELTO-warfarin
  • NOAC vs NOAC
    • 37,314 apixaban-dabigatran
    • 107,236 apixaban-XARELTO
    • 37,693 dabigatran-XARELTO

Mean follow-up was 240.1 days for XARELTO and 198.6 days for apixaban.
Note: Results for apixaban vs dabigatran are not presented here but can be found in the publication.
  • Time to first stroke/SE (IS, hemorrhagic stroke, and SE) and time to first MB (GI bleeding, ICH, and MB) at other key sites were outcomes measured.
  • The NOACs, when compared to warfarin, were all associated with lower rates of stroke/SE: apixaban (HR, 0.64; 95% CI, 0.58-0.70), dabigatran (HR, 0.82; 95% CI, 0.71-0.95), and XARELTO (HR, 0.79; 95% CI, 0.73-0.85).
  • In the NOACs compared to warfarin cohort, apixaban (HR, 0.60; 95% CI, 0.56-0.63) and dabigatran (HR 0.71; 95% CI, 0.65-0.78) were associated with lower MB and XARELTO (HR, 1.06; 95% CI, 1.02-1.10) had a higher rate of MB.
  • Rates of stroke/SE and MB across the NOACs differed and are presented below.
Comparator
Ref
HR (95% CI)
No. of Events
(Incidence per 100 PY)
Apixaban vs XARELTO (ref)
   Stroke/SE
710 (1.28)
1008 (1.47)
0.80 (0.73-0.89)
   MB
1948 (3.52)
3981 (5.88)
0.55 (0.53-0.59)
Dabigatran vs XARELTO (ref)
   Stroke/SE
334 (1.42)
309 (1.29)
1.10 (0.95-1.23)
   MB
836 (3.57)
1190 (5.02)
0.71 (0.65-0.78)
Martinez et al (2018)32 Retrospective claims database study using US MarketScan claims data from November 2011 to December 2016.
Used 1:1 PSM analyses to warfarin
Study Population
Frail patientse with NVAF
Key Demographics
  • Median age range:85-86 years in all groups
  • Median CHA2DS2-VASc and modified HAS-BLED scores were 4 and 2 in each individual DOAC vs warfarin analysis.

Study Groups (post PSM)
  • 5270 warfarin-XARELTO
  • 2700 warfarin-apixaban
  • 2784 warfarin-dabigatran

Median follow up was 0.9, 1.8, and 1.4 years for apixaban, dabigatran, and XARELTO, respectively.
  • The primary effectiveness outcome was stroke or SE including IS, hemorrhagic stroke, or SE. The primary safety outcome was MB.
  • At 2 years, neither apixaban nor dabigatran were associated with differences in the hazard of stroke or SE (HR, 0.78; 95% CI, 0.46-1.35 and HR, 0.94; 95% CI, 0.60-1.45) or MB (HR, 0.72; 95% CI, 0.49-1.06 and HR, 0.87; 95% CI, 0.63-1.19) vs warfarin.
  • XARELTO was associated with reduced hazard of stroke or SE at 2 years (HR, 0.68; 95% CI, 0.49-0.95) without significantly altering MB risk (HR, 1.07; 95% CI, 0.811.32).
Coleman et al (2017)33 Retrospective claims database study using
US Truven MarketScan data from January 2012 to June 2015.
Used 1:1 PSM cohorts
Study Population
Adult patients with NVAF and a previous history of IS/TIA newly initiated on a NOAC or warfarin
Key Demographics
  • Median age range: 72-74 years in all groups
  • 51.8%-54% were men in all groups

Study Groups (post PSM)
  • 2514 apixaban vs warfarin
  • 1962 dabigatran vs warfarin
  • 5208 XARELTO vs warfarin

Mean follow-up was 0.5 to 0.6 for all matched cohorts.
  • The primary effectiveness endpoint was a combined endpoint of IS or ICH (including intracerebral, subarachnoid, and other ICH). The primary safety endpoint was MB.
  • Apixaban and dabigatran non-significantly reduced patients’ hazard vs warfarin of the combined endpoint by 30% and 47%, respectively, and had nonsignificant effect on hazards of MB.
  • XARELTO significantly reduced IS/ICH hazard by 55% (P=0.001) and had no statistically significant effect on MB.
  • Abbreviations: AF, atrial fibrillation; CHADS2, congestive heart failure, hypertension, age >75 years, diabetes (all 1 point each) and previous stroke (2 points); CHA2DS2-VASc, congestive heart failure, hypertension, age >75 years (doubled), type 2 diabetes mellitus, previous stroke, TIA or thromboembolism (doubled), vascular disease, age of 65-75 years, and sex; CI, confidence interval; DOAC, direct oral anticoagulant; GI, gastrointestinal; HAS-BLED, Hypertension, abnormal renal/liver function, stroke, bleeding, labile inr, elderly, drugs/alcohol concomitantly; HR, hazard ratio; ICH, intracranial hemorrhage; IPTW, inverse probability of treatment weighting; IR, incidence rate; IS, ischemic stroke; MB, major bleeding; NA, not applicable; NOAC, non-vitamin K oral anticoagulant; NVAF, non-valvular atrial fibrillation; PSM, propensity score matching; PY, person-years; ref, reference; SE, systemic embolism; SES, socioeconomic status; TIA, transient ischemic attack; US, United States; VTE, venous thromboembolism.
    aCox proportional hazards models with time to an event or outcome as the response variable and the drug as the explanatory variable. HR of >1 suggests an increase in the hazard rate of an outcome with XARELTO vs the comparators.
    bThere were insufficient events to calculate a rate for these comparisons.
    cAn IPTW approach, calculated from the propensity score, was utilized to adjust for confounding and balance treatment groups. Valuespresented are after IPTW.
    dPropensity score-matched IRs and HRs of stroke/SE and MB for NOAC comparisons.
    eFrailty status was determined using the Johns Hopkins Claims-based Frailty Indicator score (≥0.20 indicating frailty).





Studies conducted outside the US
Study Objective
Patients
Outcomes
Lip et al (2025)34 
Retrospective cohort study using the French national healthcare database between January 1, 2014, and December 31, 2019.
Study Population
Patients aged ≥18 years, being treatment naïve, having a diagnosis of NVAF, and having a newly initiated anticoagulant treatment
Key Demographics (post PSM)
  • XARELTO
    • Age : 76.6 years
    • 53.4% were male
  • Apixaban
    • Age : 76.9 years
    • 53.2% were male

Study Groups (after PSM)
  • XARELTO (n=88,414)
  • Apixaban (n=88,414)

The mean follow-up duration ranged from 13.0 months to 13.8 months in both cohorts.
Outcomes
Apixaban
(Comparator)
XARELTO
(Ref)
HR (95% CI)
No. of Events
(Incidence per 100 PY)
Primary outcomes (ischemic/hemorrhagic stroke and MB)
MB
2.15
(2.06, 2.24)
3.45
(3.34, 3.57)
0.63
(0.59-0.66)
   GIB
0.76
(0.71, 0.82)
1.42
(1.35, 1.50)
0.54
(0.49-0.59)
   ICH
0.54
(0.50, 0.59)
0.60
(0.56, 0.65)
0.89
(0.80-1.01)
   Bleeding at
   other sites
0.90
(0.84, 0.96)
1.51
(1.44, 1.59)
0.60
(0.55-0.65)
Stroke/SE
1.51
(1.44, 1.59)
1.69
(1.61, 1.77)
0.90
(0.84-0.96)
   SE
0.45
(0.41, 0.49)
0.46
(0.42, 0.51)
0.97
(0.85-1.10)
   Stroke
   (ischemic/
   hemorrhagic)
1.06
(1.00, 1.13)
1.23
(1.16, 1.30)
0.87
(0.80-0.95)
      Ischemic
      stroke
0.80
(0.75, 0.86)
0.90
(0.84, 0.96)
0.90
(0.82-0.99)
      Hemorrhagic
      stroke
0.27
(0.24, 0.31)
0.34
(0.31, 0.38)
0.80
(0.69-0.94)
Douros et al (2024)35 Active-comparator, new-user, population-based cohort study using
the CPRD (UK) and RAMQ (Quebec, Canada) between January 1, 2011 to June 22, 2020 in the CPRD and December 31, 2020 in the RAMQ.
Used IPTW
Study Population
Adult patients with NVAF and liver disease initiating a DOAC or VKA
Key Demographics/Study Groups
Apixaban vs XARELTO
  • 4414 patients were included in the apixaban group (CPRD, N=1696, mean age [SD]: 72.5 [10.6] years; RAMQ, N=2718, mean age [SD]: 75.2 [9.8] years)
  • 2497 patients were included in the XARELTO group (CPRD, N=1264, mean age [SD]: 71.1 [11.1] years; RAMQ, N=1233, mean age [SD]: 71.7 [9.6] years).
Primary outcomes (ischemic stroke/TIA and MB)
Apixabana
XARELTOa
Events/n
Rate per 1000 PY
Events/n
Rate per 1000 PY
Ischemic stroke/TIA
      CPRD (UK)
15/1696
9.17
16/1264
10.64
aHR (95% CI)
0.67 (0.33-1.36)
1.00 (ref)
      RAMQ (Quebec)
76/2718
19.35
37/1233
19.46
aHR (95% CI)
0.92 (0.61-1.37)
1.00 (ref)
MB
      CPRD (UK)
85/1696
53.17
96/1264
66.29
aHR (95% CI)
0.71 (0.53-0.95)
1.00 (ref)
      RAMQ (Quebec)
283/2718
75.05
147/1233
80.90
aHR (95% CI)
0.85 (0.70-1.05)
1.00 (ref)
Secondary outcome (all-cause mortality)36
CPRD (UK)
127/1696
77.09
98/1264
64.55
aHR (95% CI)
0.97 (0.75-1.26)
1.00 (ref)
RAMQ (Quebec)
467/2718
117.12
188/1233
96.95
aHR (95% CI)
0.99 (0.84-1.18)
1.00 (ref)
Talmor-Barkan et al (2023)37 Retrospective, observational study using the Israeli CHS database between January 1, 2014 to January 1, 2020
Used 1:1 PSM
Study Population
Patients aged 20-100 years with AF
Key Demographics
  • Mean age was 76 years in both XARELTO and apixaban groups
  • CHA2DS2-VASc (mean) was 4.1 in both XARELTO and apixaban groups

Study Groups (post PSM)
  • XARELTO (N=15,668)
  • Apixaban (N=15,668)

Note: Results for XARELTO vs dabigatran are not presented here but can be found in the publication.
Outcomesb
XARELTO
Apixaban
HR
(95% CI); P value
Efficacy outcomes
All-cause mortality
15.7/1000 PY
17.5/1000 PY
0.88 (0.78-0.99); 0.037
Ischemic stroke
49.3/1000 PY
55.8/1000 PY
0.92 (0.86-0.99); 0.024
Safety outcomes
ICH
9.4/1000 PY
11.6/1000 PY
0.86 (0.74-1.0); 0.044
GI bleeding
9.5/1000 PY
7.9/1000 PY
1.22 (1.03-1.44); 0.016
Jaksa et al (2022)38 Observational study using THIN database (UK) between July 2014 and December 2020
Used 1:1 PMS
Study Population
Adult patients with NVAF newly initiated on NOACs for stroke prevention
Key Demographics
  • XARELTO
    • Mean (SD) age 76.8 (8.40) years
    • Mean (SD) CHA2DS2VASc score 3.45 (1.09)
  • Apixaban
    • Mean (SD) age 77.1 (8.69) years
    • Mean (SD) CHA2DS2VASc score 3.44 (1.09)

Study groups (post PSM)
  • Apixaban (N=1839)
  • XARELTO (N=1839)

Median follow-up in the ITT population was 779 days (322-1284) in the XARELTO group and 845 (340-1368) days in the apixaban group.
Outcomes
XARELTO
Apixaban
aHR
(95% CI)
Events/N
Rate per 1000 PY
Events/N
Rate per 1000 PY
Primary outcome
Stroke
57/1839
13.48
56/1839
12.47
0.93
(0.64-1.34)


Secondary outcomes
All-cause mortalityc
259/1837
60.81
288/1837
62.72
1.03 (0.87-1.22)
MI
24/1839
5.63
24/1839
5.28
0.95 (0.54-1.68)
TIA
28/1839
6.57
30/1839
6.64
1.03 (0.61-1.72)
MB event
183/1839
45.86
117/1839
26.72
0.60 (0.47-0.75)
Composite of
angina/MI/stroke
96/1839
23.12
97/1839
21.93
0.96
(0.72-1.27)
Andersson et al (2018)39 Historical register-based cohort study using the National Patient Register and the Register of Medicinal Product Statistics (Danish) between July 1, 2013 and March 31, 2016
Used 1:1 PSM
Study Population
Patients aged ≥45 years with a recent diagnosis of NVAF and who were new users of standard dose DOACs
Key Demographics
  • Mean age range: 67.5-72.0 years in all cohorts

Study Groups (post PSM)
  • XARELTO (N=3676) vs apixaban cohort (N=3676)
  • XARELTO (N=2720) vs dabigatran (N=2720) cohort
  • apixaban (N=3235) vs dabigatran (N=3235) cohort

Note: Results for dabigatran vs apixaban are not presented here but can be found in the publication.
  • Primary efficacy outcome: hospital admission with a primary or secondary diagnosis of stroke/SE.
  • Primary safety outcome: hospital admission with a diagnosis of intracranial bleeding, GI bleeding (bleeding ulcer, hematemesis or melena) or other serious bleeding (anemia caused by bleeding, bleeding of unknown origin, bleeding of the respiratory or urinary tract, peritoneal, retinal or orbital bleeding).
Comparator
Ref
HR (95% CI)
Event Rate per 100 PY
Apixaban vs XARELTO (ref) (n=7352)
   Stroke/SE
3.19
2.57
1.25
(0.87-1.79)
   MB
3.37
3.87
0.88
(0.64-1.22)
   Death
5.66
8.11
0.71
(0.56-0.89)
Dabigatran vs XARELTO (ref) (n=5440)
   Stroke/SE
1.54
1.91
1.17
(0.69-1.96)
   MB
2.54
3.57
1.35
(0.91-2.00)
   Death
3.18
5.36
1.61
(1.15-2.26)
Abbreviations: AF, atrial fibrillation; aHR, adjusted hazard ratio; CHA2DS2-VASc, congestive heart failure, hypertension, age >75 years (doubled), type 2 diabetes mellitus, previous stroke, TIA or thromboembolism (doubled), vascular disease, age of 65-75 years, and sex; CHS, Clalit Health Services; CI, confidence interval; CPRD, Clinical Practice Research Datalink; DOAC, direct oral anticoagulant; GI, gastrointestinal; HR, hazard ratio; ICH, intracranial hemorrhage; IPTW, inverse probability of treatment weighting; ITT, intention-to-treat; MB, major bleeding; MI, myocardial infarction; NOAC, non-vitamin K oral anticoagulant; NVAF, non-valvular atrial fibrillation; PSM, propensity score matching; PY, person-years; RAMQ, Régie de l'assurance maladie du Québec; ref, reference; SD, standard deviation; SE, systemic embolism; THIN, The Health Improvement Network; TIA, transient ischemic attack; UK, United Kingdom; US, United States; VKA, vitamin K antagonist.aIPTW was applied based on propensity scores to adjust for potential confounders and covariates.
bEffectiveness outcomes were mortality, ischemic stroke, MI, or SE. Safety outcomes were GI bleeding, ICH, bleeding from other sites, and overall bleeding (GI bleeding, ICH, and bleeding from other sites). Additional results can be found in the publication.
cIn analysis of all-cause mortality, patients were followed until occurrence of outcome (death), end of study period (December 2020) or the later date of end of patient registration and any recorded death within 90 days of end of patient registration. Propensity score matched sample size for analysis of all-cause mortality differs from sample size in analysis of other outcomes because of differences in censoring criteria, which impact a small number of patients' eligibility for inclusion in analysis at the start of follow-up.

LITERATURE SEARCH

A literature search of MEDLINE®, EMBASE®, BIOSIS Previews®, DERWENT® (and/or other resources, including internal/external databases) was conducted on 04 July 2025.

 

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