Medical inquiries

Connect with my medical science liaison

Chat live

Available Monday - Friday 9AM - 4:30PM ET

Call me now

Available Monday - Friday 9AM - 7:30PM ET

Email your inquiry

Call 1-800-526-7736

Available Monday - Friday 9AM - 8PM ET

Live video

Available Monday - Friday 9AM - 4:30PM ET

This information is intended for US healthcare professionals to access current scientific information about J&J Innovative Medicine products. It is prepared by Medical Information and is not intended for promotional purposes, nor to provide medical advice.

XARELTO® (rivaroxaban)

Medical Information

+ Save link

Adverse Event - Comparison of Major Bleeding Events in Patients With NVAF Receiving DOACs

Last Updated: 09/10/2024

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 DOACs.¹^,²
- For patients aged <65 years, data have been summarized in Table: Sentinel Bleeding Rates in Patients With NVAF 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) for intracranial hemorrhage (ICH), 1.91 (95% CI, 1.56-2.34) for major gastrointestinal (GI) bleeding, and 1.92 (95% CI, 1.54-2.39) for major extracranial bleeding (MEB).¹
  - In a comparison of XARELTO vs dabigatran, the HR was 1.18 (95% CI, 0.52-2.67) for ICH, 1.32 (95% CI, 0.89-1.96) for major GI bleeding, and 1.42 (95% CI, 0.98-2.07) for MEB.¹
- For patients aged ≥65 years, data have been summarized in Table: Sentinel Bleeding Rates in Patients With NVAF Aged ≥65 Years.
  - In a comparison of XARELTO vs apixaban, the HR was 1.28 (95% CI, 0.99-1.67) and 1.23 (95% CI, 0.96-1.58; by inverse probability of treatment weighted pairwise comparison [IPTW]) for ICH, 2.32 (95% CI, 2.07-2.59) and 2.35 (95% CI, 2.11-2.61; by IPTW) for major GI bleeding, and 2.29 (95% CI, 2.06-2.55) and 2.33 (95% CI, 2.11-2.58; by IPTW) for MEB.²
  - In a comparison of XARELTO vs dabigatran, the HR was 1.67 (95% CI, 1.29-2.17) and 1.58 (95% CI, 1.23-2.03; by IPTW) for ICH, 1.17 (95% CI, 1.08-1.28) and 1.16 (95% CI, 1.07-1.25; by IPTW) for major GI bleeding, and 1.21 (95% CI, 1.12-1.32) and 1.20 (95% CI, 1.11-1.30; by IPTW) for MEB.²
Currently, no randomized, controlled, head-to-head trials evaluating the use of direct oral anticoagulants (DOACs) in nonvalvular atrial fibrillation (NVAF) have been reported in the literature. Data from real-world studies (Table: Summary of Bleeding Events in Select Real-World Studies) is included in this response. Systematic reviews and meta-analyses identified during literature review are included in the references section.³^-⁶

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.⁷
Sentinel reports containing data on major bleeding events in patients with NVAF receiving XARELTO are summarized below. Each 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.¹^,²

Sentinel Bleeding Rates in Patients With NVAF Aged <65 Years¹

Bradley et al (2024)¹
Study Design	Results
	Cohorts	HR (95% CI) by IPTW
	Cohorts	MEB	GI Bleeding	ICH
Retrospective new-user cohort study among standard dose NOAC users Data source: Medicare Outcomes: Incidence of MEB, GI bleeding, and ICH Duration: 10/19/2020-2/28/2022 Patients with kidney replacement, DVT, PE, joint replacement, mitral stenosis, valve replacement or repair, or receiving dialysis were excluded.	XARELTO vs apixaban (n=57,932 vs 96,057)	1.92 (1.54-2.39)	1.91 (1.56-2.34)	1.63 (0.99-2.70)
	XARELTO vs dabigatran (n=57,399 vs 20,188)	1.42 (0.98-2.07)^a	1.32 (0.89-1.96)^a	1.18 (0.52-2.67)^a
Abbreviations: CI, confidence interval; DVT, deep vein thrombosis, GI, gastrointestinal; HR, hazard ratio; ICH, intracranial hemorrhage; IPTW, inverse probability of treatment weighted pairwise comparisons; MEB, major extracranial bleeding; NOAC, non-vitamin K antagonist oral anticoagulants; NVAF, nonvalvular atrial fibrillation; PE, pulmonary embolism. ^aStatistical significance was not achieved.

Sentinel Bleeding Rates in Patients With NVAF Aged ≥65 Years²

Bradley et al (2022)²
Study Design	Results
	Cohorts	HR (95% CI)
	Cohorts	MEB	Major GI Bleeding	ICH
Retrospective new-user cohort study Outcomes: Risk of MEB, GI bleeding, ICH, and thromboembolic stroke using IPTW vs PSM Duration: 10/19/2010-9/30/2015 Patients with kidney replacement, DVT, PE, joint replacement, mitral stenosis, valve replacement or repair, or receiving dialysis were excluded.	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
	XARELTO vs dabigatran by IPTW (n=110,111 vs 84,481)	1.20 (1.11-1.30)	1.16 (1.07-1.25)	1.58 (1.23-2.03)
	XARELTO vs dabigatran by PSM (n=82,326)	1.21 (1.12-1.32)	1.17 (1.08-1.28)	1.67 (1.29-2.17)
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

Some key limitations of the real-world data summarized below include⁸^,⁹:
- 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 outcomes.
- Composition of the population may limit the generalizability of the findings.

Summary of Bleeding Events in Select Real-World Studies¹⁰^-³²

Author (Year)	Methods				Results
Author (Year)	Study Design (Number of Patients on XARELTO)	Data Source^a	Key Outcomes	Study Duration	Bleeding event	HR (95% CI; P-Value^b)
XARELTO vs Apixaban
Talmor-Barkan (2023)¹⁰	Retrospective, nationwide, PSM-based observational study (n=15,682)	Clalit Health Services database (Israel)	Efficacy: mortality, ischemic stroke, myocardial infarction, or systemic embolism Safety: GI bleeding, ICH, bleeding from other sites, and overall bleeding^d	1/1/2014-1/1/2020	Overall bleeding	1.02 (0.92-1.13; P=0.652)
					ICH	0.86 (0.74-1.0; P=0.044)
					GI	1.22 (1.03-1.44; P=0.016)
					Other bleeding	1.18 (0.94-1.48; P=0.163)
Ray et al (2021)¹¹	Retrospective cohort study (n=227,572)	Medicare database	Major ischemic (stroke/systemic embolism) or hemorrhagic (ICH/other intracranial bleeding/fatal extracranial bleeding leading to death ≤30 days of onset) events	1/1/2013-11/30/2018	Fatal extracranial bleeding	1.41 (1.18-1.70)
					Nonfatal extracranial bleeding	2.07 (1.99-2.15)
					Other ICH	1.09 (0.98-1.22)
					GI bleeding	2.09 (2.01-2.18)
Graham et al (2019)¹²	Retrospective new-user cohort study (n=106,389)	Medicare database	Incidence of hospitalized MEB^c, GI bleeding, ICH, and thromboembolic stroke^d	10/2010-9/2015	MEB	2.70 (2.38-3.05)
					GI bleeding	2.83 (2.47-3.25)
					ICH	1.21 (0.94-1.55)
Tepper et al (2018)¹³	Retrospective claims observational cohort study (n=30,529)	Truven MarketScan Commercial Claims database Encounter and Medicare Supplemental & Coordination of Benefits Early View database	Comparative safety including MB, defined using patient claims data	1/1/2013-10/31/2014	Any inpatient MB	1.43 (1.17-1.74; P<0.01)
					Inpatient ICH	1.29 (0.71-2.35; P=0.41)
					Inpatient GI bleeding	1.51 (1.18-1.92; P<0.01)
					Other inpatient MB	1.58 (1.13-2.22; P<0.01)
Amin et al (2017)¹⁴	Real-world data comparison study (n=20,804)	Medicare database	Risks of stroke or systemic embolism Risk of MB	1/1/2013-12/31/2014	MB	2.17 (1.91-2.48; P<0.0001)
Lip et al (2016)¹⁵	Retrospective cohort study (n=17,860)	MarketScan commercial database Medicare supplemental database	Risk of a first MB event^d	1/1/2012-9/30/2014	MB	2.05 (1.50-2.79)
Lip et al (2015)¹⁶	Retrospective cohort study (n=10,050)	MarketScan commercial database Medicare supplemental database	MB risk, defined as bleeding requiring hospitalization and inpatient/outpatient bleeding	1/1/2013-12/31/2013	Inpatient MB	2.19 (1.26-2.79; P=0.0052)
Lip et al (2015)¹⁶	Retrospective cohort study (n=10,050)			1/1/2013-12/31/2013	Outpatient or inpatient MB	1.70 (1.26-2.29; P=0.0006)
Lin et al (2015)¹⁷	Real-world study (n=6,407)	Humedica de-identified Electronic Health Record data	Bleeding rates^d	1/1/2013-6/30/2014	MB	1.46 (1.23-1.75)
Deitelzweig et al (2015)¹⁸	Real-world study (67.4% of 9150 total patients)	IQVIA PharMetrics Plus database	Bleeding All-cause hospitalization Economic outcomes	1/2012-1/2014	MB	1.8 (1.4-2.2; P<0.0001)
Apixaban vs XARELTO
Mahesri et al (2024)³¹	New-user comparative cohort study designed to replicate the COBRA-AF and COBRA-VTE studies COBRRA-AF (n=177,866) COBRRA-VTE (n=14,292)	Optum Clinformatics Merative Marketscan Medicare	Composite MB and clinically relevant non-major bleeding	2003-2019	MB and clinically relevant non-major bleeding (PSM)	COBRRA-AF 0.69 (0.66-0.71) COBRRA-VTE 0.67 (0.58-0.78)
Jaksa et al (2022)¹⁹	Comparative cohort study (n=1,985)	The Health Improvement Network database (UK)	Ischemic or hemorrhagic stroke and MB, defined as a composite of major ICH, GI bleeding, and urogenital bleeding per Read Medical Codes and ICD-10-CM diagnosis codes	7/1/2014-12/31/2020	MB	0.60 (0.47-0.75)
Lip et al (2022)²⁰	Retrospective observational study (n=38,246)	Medicare database IBM Watson Health MarketScan Commercial Claims and Encounter database IQVIA PharMetrics Plus database Optum Clinformatics Data Mart database Humana Research database	Effectiveness: stroke or systemic embolism Safety: GI bleeding, ICH, MB in other sites, defined by predefined diagnosis codes	1/1/2013-6/30/2019	MB in other sites	0.51 (0.46-0.57; P<0.0001)
					ICH	0.97 (0.82-1.15; P=0.7284)
					GI bleeding	0.64 (0.59-0.68; P<0.0001)
Fralick et al (2020)²¹	Retrospective new-user cohort study (n=40,706)	Optum Clinformatics Data Mart database	Effectiveness: ischemic stroke or systemic embolism Safety: ICH or GI bleeding, defined by primary diagnosis codes	12/28/2012-1/1/2019	Pooled ICH or GI bleeding (PSM)	0.58 (0.52-0.66)
					GI bleeding (PSM)	0.52 (0.45-0.59)
					ICH (PSM)	0.91 (0.71-1.18)
Ganse et al (2020)²²	Observational study (31.1% of 321,501 total patients)	Claims data from the National Health System (France)	Effectiveness: stroke, systemic thromboembolic events Safety: MB events leading to hospitalization^e All-cause mortality	1/2014-12/2016	Other MB	0.64 (0.57-0.71)
					ICH	0.87 (0.75-1.01)
					GI bleeding	0.63 (0.56-0.70)
Lip et al (2018)²³	Retrospective observational study (n=153,002)	Medicare database Four commercial claims databases	Time to first stroke or systemic embolism (including ischemic and hemorrhagic stroke) Time to first MB (including GI bleeding, ICH, MB at other key sites)^e	1/1/2013-9/30/2015	MB	0.55 (0.53-0.59)
Andersson et al (2018)²⁴	Historical register-based cohort study (n=3,676)	National Patient Register Register of Medicinal Product Statistics Register of Medicinal Product Statistics (Denmark)	Effectiveness: stroke or systemic embolism Safety: any MB, defined as a hospital admission with a diagnosis of intracranial bleeding, GI bleeding, or other serious bleeding	7/1/2013-3/31/2016	MB	0.88 (0.64-1.22)
Deitelzweig et al (2017)²⁵	Retrospective cohort study^f	Optum Clinformatics Data Mart database MarketScan database IQVIA PharMetrics Plus database Humana Research database	Risks of stroke or systemic embolism Risk of MB, identified using the first listed diagnosis of inpatient claims	1/1/2013-9/30/2015	MB	0.61 (0.56-0.67; P<0.001)
Amin et al (2015)²⁶	Retrospective study (n=8,740)	Optum Research database	Risk of MB^c Health care costs	1/1/2013-31/12/2014	MB	0.69 (0.59-0.81)
Noseworthy et al (2016)²⁷	Retrospective study^f	Administrative claims data from Optum Labs Data Warehouse	Effectiveness: stroke and systemic embolism Safety: first inpatient admission for MB, including GI bleeding, intracranial bleeding, and bleeding from other sites	10/1/2010-2/28/2015	MB	0.39 (0.28-0.54; P<0.001)
Amin et al (2015)²⁸	Real-world data comparison study (n=13,370)	A large national commercial and Medicare advantage insurance database	Stroke risk reduction MB^c risk reduction Related medical costs	1/1/2013-12/31/2014	MB	0.71 (0.62-0.82)
Katayama et al (2024)³²	Retrospective observational cohort study (n=97,320)	Medical, prescription and DPC claims from NDB	Effectiveness: stroke or systemic embolism Safety: clinically significant bleeding^g(any fatal bleeding or bleeding in a critical area/organ including ICH)	3/2015-2/2019	Clinically significant bleeding	0.95 (0.93-0.97; log rank P= 0.0005)
XARELTO vs Dabigatran
Talmor-Barkan (2023)¹⁰	Retrospective, nationwide, PSM-based observational study (n=15,682)	Clalit Health Services database (Israel)	Efficacy: mortality, ischemic stroke, myocardial infarction, or systemic embolism Safety: GI bleeding, ICH, bleeding from other sites, and overall bleeding^d	1/1/2014-1/1/2020	Overall bleeding	0.93 (0.79-1.09; P=0.353)
					ICH	0.81 (0.64-1.02; P=0.065)
					GI bleeding	1.11 (0.86-1.44; P=0.447)
					Other bleeding	0.99 (0.65-1.5; P=0.964)
Graham et al (2019)¹²	Retrospective new-user cohort study (n=106,389)	Medicare database	Incidence of hospitalized MEB^c, GI bleeding, ICH, and thromboembolic stroke^d	10/2010-9/2015	MEB	1.32 (1.21-1.45)
					GI bleeding	1.27 (1.16-1.40)
					ICH	1.71 (1.35-2.17)
Andersson et al (2018)²⁴	Historical register-based cohort study (n=3,676)	National Patient Register Register of Medicinal Product Statistics Register of Medicinal Product Statistics (Denmark)	Effectiveness: stroke or systemic embolism Safety: any MB, defined as a hospital admission with a diagnosis of intracranial bleeding, GI bleeding, or other serious bleeding	7/1/2013-3/31/2016	MB	1.35 (0.91-2.00)
Graham et al (2016)²⁹	Retrospective new-user cohort study (n=66,651)	Medicare database	Risks of thromboembolic stroke, ICH, MEB (defined as fatal bleeding event, a hospitalized bleeding event requiring transfusion, or hospitalization with hemorrhage into an extracranial critical site)^d	11/4/2011-6/30/2014	MEB	1.48 (1.32-1.67; P<0.001)
					ICH	1.65 (1.20-2.26; P=0.002)
					GI bleeding	1.40 (1.23-1.59 P<0.001)
Noseworthy et al (2016)²⁷	Retrospective study^f	Administrative claims data from Optum Labs Data Warehouse	Effectiveness: stroke and systemic embolism Safety: first inpatient admission for MB, including GI bleeding, intracranial bleeding, and bleeding from other sites	10/1/2010-2/28/2015	MB	1.30 (1.10-1.53; P<0.01)
Dabigatran vs XARELTO
Lip et al (2022)²⁰	Retrospective observational study (n=38,246)	Medicare IBM Watson Health MarketScan Commercial Claims and Encounter database IQVIA PharMetrics Plus database Optum Clinformatics Data Mart Humana Research database	Effectiveness: stroke or systemic embolism Safety: GI bleeding, ICH, MB in other sites, defined by predefined diagnosis codes	1/1/2013-6/30/2019	MB in other sites	0.92 (0.79-1.07; P=0.2577)
					ICH	0.89 (0.67-1.17; P=0.4020)
					GI bleeding	0.81 (0.73-0.90; P<0.0001)
Villines et al (2019)³⁰	Retrospective cohort study (n=12,763)	US Department of Defense Military Health System database	Efficacy: hemorrhagic or ischemic stroke Safety: MB including hemorrhagic stroke, major intracranial bleeding, or MEB^d	7/2011-6/2016	MB	0.82 (0.70-0.97; P=0.018)
Lip et al (2018)²³	Retrospective observational study (n=153,002)	Medicare database Four commercial claims databases	Time to first stroke or systemic embolism (including ischemic and hemorrhagic stroke) Time to first MB (including GI bleeding, ICH, MB at other key sites)^e	1/1/2013-9/30/2015	MB	0.71 (0.65-0.78)
Deitelzweig et al (2017)²⁵	Retrospective cohort study^f	Optum Clinformatics Data Mart database MarketScan database IQVIA PharMetrics Plus database Humana Research database	Risks of stroke or systemic embolism and MB, identified using the first listed diagnosis of inpatient claims	1/1/2013-9/30/2015	MB	0.73 (0.63-0.84; P<0.001)
Katayama et al (2024)³²	Retrospective observational cohort study (n=97,320)	Medical, prescription and DPC claims from NDB	Effectiveness: stroke or systemic embolism Safety: clinically significant bleeding^g(any fatal bleeding or bleeding in a critical area/organ including ICH)	3/2015-2/2019	Clinically significant bleeding	1.04 (1.01-1.07; log rank P= 0.2152)
XARELTO vs Edoxaban
Katayama et al (2024)³²	Retrospective observational cohort study (n=97,320)	Medical, prescription and DPC claims from NDB	Effectiveness: stroke or systemic embolism Safety: clinically significant bleeding^g(any fatal bleeding or bleeding in a critical area/organ including ICH)	3/2015-2/2019	Clinically significant bleeding	0.99 (0.97-1.01; log rank P= 0.5778)
Abbreviations: CI, confidence interval; DPC, Diagnosis Procedure Combination; GI, gastrointestinal; HR, hazard ratio; ICD-9-CM, International Classification of Diseases, 9^th Revision, Clinical Modification; ICH, intracranial hemorrhage; MB, major bleeding; MEB, major extracranial bleeding; NDB, National Database of Health Insurance Claims and Specific Health Checkups of Japan; PSM, propensity score matching; UK, United Kingdom; US, United States.^aAll databases are based in the US, unless otherwise specified. ^bP-values are reported only wherever available. ^cBased on the Cunningham algorithm.^dDefined using ICD-9-CM diagnosis codes used in hospital claims. ^eDefined by hospital discharge diagnoses.^fn value is not separately reported for the XARELTO cohort.^gDefined using International Society on Thrombosis and Haemostasis criteria.

LITERATURE SEARCH

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) pertaining to this topic was conducted on 30 August 2024.

References

Show

1	Bradley MC, Simon AL, Kolonoski J, et al. Comparative bleeding risks among NOAC users for nonvalvular atrial fibrillation aged <65 years in the Sentinel System. Poster presented at: International Conference on Pharmacoepidemiology & Therapeutic Risk Management (ICPE); August 24-28, 2024; Berlin, Germany.
2	Bradley MC, Menzin T, Kolonoski J, et al. Inverse probability treatment weighting versus propensity score matching in the Sentinel system: a test case. Poster presented at: International Conference on Pharmacoepidemiology & Therapeutic Risk Management (ICPE); August 26-28, 2022; Copenhagen, Denmark.
3	Deitelzweig S, Farmer C, Luo X, et al. Comparison of major bleeding risk in patients with non-valvular atrial fibrillation receiving direct oral anticoagulants in the real-world setting: a network meta-analysis. Curr Med Res Opin. 2018;34(3):487-498.
4	Li G, Lip GYH, Holbrook A, et al. Direct comparative effectiveness and safety between non-vitamin K antagonist oral anticoagulants for stroke prevention in nonvalvular atrial fibrillation: a systematic review and meta-analysis of observational studies. Eur J Epidemiol. 2019;34(2):173-190.
5	Mamas MA, Batson S, Pollock KG, et al. Meta-analysis comparing apixaban versus rivaroxaban for management of patients with nonvalvular atrial fibrillation. Am J Cardiol. 2022;166:58-64.
6	Durand M, Schnitzer ME, Pang M, et al. Effectiveness and safety among direct oral anticoagulants in nonvalvular atrial fibrillation: a multi‐database cohort study with meta‐analysis. Br J Clin Pharmacol. 2021;87(6):2589-2601.
7	FDA’s Sentinel Initiative. Accessed 2024-03-29. Available via: https://www.fda.gov/safety/fdas-sentinel-initiative
8	De Lusignan S, Crawford L, Munro N. Creating and using real-world evidence to answer questions about clinical effectiveness. J Innov Health Inform. 2015;22(3):368-373.
9	Nallamothu BK, Hayward RA, Bates ER. Beyond the randomized clinical trial: the role of effectiveness studies in evaluating cardiovascular therapies. Circulation. 2008;118(12):1294-1303.
10	Talmor-Barkan Y, Yacovzada NS, Rossman H, et al. Head-to-head efficacy and safety of rivaroxaban, apixaban, and dabigatran in an observational nationwide targeted trial. Eur Heart J Cardiovasc Pharmacother. 2022;9(1):26-37.
11	Ray WA, Chung CP, Stein CM, et al. Association of rivaroxaban vs apixaban with major ischemic or hemorrhagic events in patients with atrial fibrillation. JAMA. 2021;326(23):2395-2404.
12	Graham DJ, Baro E, Zhang R, et al. Comparative stroke, bleeding, and mortality risks in older Medicare patients treated with oral anticoagulants for nonvalvular atrial fibrillation. Am J Med. 2019;132(5):596-604.
13	Tepper PG, Mardekian J, Masseria C, et al. Real-world comparison of bleeding risks among non-valvular atrial fibrillation patients prescribed apixaban, dabigatran, or rivaroxaban. PLoS One. 2018;13(11):e0205989.
14	Amin AN, Keshishian A, Trocio J, et al. Risk of stroke and major bleeding for dabigatran, rivaroxaban, and warfarin compared to apixaban among non-valvular atrial fibrillation patients in the United States Medicare population [abstract]. Circulation. 2017;136(1). Abstract 15949.
15	Lip GYH, Keshishian A, Kamble S, et al. Real world comparison of major bleeding risk among non-valvular atrial fibrillation patients newly initiated on apixaban, warfarin, dabigatran or rivaroxaban: a 1:1 propensity-score matched analysis [abstract]. J Am Coll Cardiol. 2016;67(13). Abstract 882.
16	Lip GYH, Pan X, Kamble S, et al. Real world comparison of major bleeding risk among non-valvular atrial fibrillation patients newly initiated on apixaban, dabigatran, rivaroxaban or warfarin [abstract]. Eur Heart J. 2015;36(1):1085. Abstract 6217.
17	Lin I, Masseria C, Mardekian J, et al. Real-world bleeding risk among non-valvular atrial fibrillation (NVAF) patients prescribed apixaban, dabigatran, rivaroxaban and warfarin: analysis of electronic health records [abstract]. Eur Heart J. 2015;36(1):1084. Abstract 6215.
18	Deitelzweig S, Bruno A, Tate N, et al. Major bleeding, hospitalisation rates and healthcare costs among non-valvular atrial fibrillation patients naive to oral anticoagulation and newly treated with novel oral anticoagulants [abstract]. Eur Heart J. 2015;36(1):338. Abstract 1971.
19	Jaksa A, Gibbs L, Kent S, et al. Using primary care data to assess comparative effectiveness and safety of apixaban and rivaroxaban in patients with nonvalvular atrial fibrillation in the UK: an observational cohort study. BMJ Open. 2022;12(10):e064662.
20	Lip GYH, Keshishian A, Kang A, et al. Effectiveness and safety of oral anticoagulants in non-valvular atrial fibrillation patients with prior bleeding events: a retrospective analysis of administrative claims databases. J Thromb Thrombolysis. 2022;54(1):33-46.
21	Fralick M, Colacci M, Schneeweiss S, et al. Effectiveness and safety of apixaban compared with rivaroxaban for patients with atrial fibrillation in routine practice a cohort study. Ann Intern Med. 2020;172(7):463-473.
22	Ganse EV, Danchin N, Mahé I, et al. Comparative safety and effectiveness of oral anticoagulants in nonvalvular atrial fibrillation: the NAXOS study. Stroke. 2020;51(7):2066-2075.
23	Lip GYH, Keshishian A, Li X, et al. Effectiveness and safety of oral anticoagulants among nonvalvular atrial fibrillation patients: the ARISTOPHANES study. Stroke. 2018;49(12):2933-2944.
24	Andersson NW, Svanström H, Lund M, et al. Comparative effectiveness and safety of apixaban, dabigatran, and rivaroxaban in patients with non-valvular atrial fibrillation. Int J Cardiol. 2018;268:113-119.
25	Deitelzweig S, Keshishian A, Li X, et al. Effectiveness and safety of apixaban, dabigatran, and rivaroxaban among non-valvular atrial fibrillation patients: a propensity score matched analysis of four large databases [abstract]. Circulation. 2017;136. Abstract 16462.
26	Amin AN, Keshishian A, Xie L, et al. Comparison of major-bleeding risk and health care costs among treatment-naïve non-valvular atrial fibrillation patients initiating apixaban, dabigatran, rivaroxaban or warfarin [abstract]. Circulation. 2015;132(Suppl. 3). Abstract 19672.
27	Noseworthy PA, Yao X, Abraham NS, et al. Direct comparison of dabigatran, rivaroxaban, and apixaban for effectiveness and safety in nonvalvular atrial fibrillation. Chest. 2016;150(6):1302-1312.
28	Amin AN, Keshishian A, Xie L, et al. Early comparison of major bleeding, stroke and associated medical costs among treatment-naive non-valvular atrial fibrillation patients initiating apixaban, dabigatran, rivaroxaban or warfarin. Blood. 2015;126(23):745.
29	Graham DJ, Reichman ME, Wernecke M, et al. Stroke, bleeding, and mortality risks in elderly medicare beneficiaries treated with dabigatran or rivaroxaban for nonvalvular atrial fibrillation. JAMA Intern Med. 2016;176(11):1662-1671.
30	Villines TC, Ahmad A, Petrini M, et al. Comparative safety and effectiveness of dabigatran vs. rivaroxaban and apixaban in patients with non-valvular atrial fibrillation: a retrospective study from a large healthcare system. Eur Heart J Cardiovasc Pharmacother. 2019;5(2):80-90.
31	Mahesri M, Schneeiweiss S, Lin KJ, et al. Predicting findings of two on-going phase IV randomized trials of direct oral anticoagulants: an RCT-DUPLICATE study. Poster presented at: International Society for Pharmacoepidemiology (ISPE); August 26, 2024; Berlin, Germany.
32	Katayama S, Aoki Y, Akita A, et al. Direct comparison of the effectiveness and safety among direct oral anticoagulants and warfarin in Japanese patients: nationwide cohort study in Japan. [Epub ahead of print]. 2024. doi:10.1002/cpt.3331.