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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)

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

Last Updated: 09/19/2024

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 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 direct oral anticoagulants (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)
	Cohorts	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
Bradley et al (2022)²	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 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
Mahesri et al (2024)¹⁴ 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-major bleeding) COBRRA-AF In patients with AF, the risk of major and clinically relevant non-major bleeding was decreased 31% with apixaban compared to XARELTO (HR, 0.69; 95% CI, 0.66-0.71).
Lawal et al (2023)¹⁵ 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)^a						HR (95% CI)^a
		Primary outcomes (hospitalization for ischemic stroke/SE and major bleeding)			XARELTO (N=2211)			Apixaban (N=2721)			HR (95% CI)^a
		Ischemic stroke/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 ischemic stroke/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 major bleeding 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)¹⁶ Retrospective, observational data analysis using 5 insurance databases (Fee-for-Service Medicare data from the U.S. 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.				Comparator^b			Ref^b
					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 incidence rates per 100 PY of stroke/SE, including ischemic stroke, hemorrhagic stroke, and SE, for XARELTO, apixaban, dabigatran, and warfarin were 2.5, 2.7, 2.6, and 2.9, respectively. Similarly, the unadjusted incidence rates per 100 PY of major bleeding, including GI bleeding, ICH, and major bleeding 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)¹⁷ 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) Ischemic Stroke 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)¹⁸ 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 propensity score matching, incidence rate of ischemic stroke 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)¹⁹ 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.²⁰^-²⁷)	Study Population Patients with NVAF newly initiating apixaban, dabigatran, rivaroxaban, 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 (ischemic stroke, hemorrhagic stroke, and SE) and time to first MB (gastrointestinal bleeding, intracranial hemorrhage 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 major bleeding and XARELTO (HR, 1.06; 95% CI, 1.02-1.10) had a higher rate of major bleeding. Rates of stroke/SE and major bleeding across the NOACs differed and are presented below.
			Comparator				Ref			HR (95% CI)
			No. of Events (Incidence per 100 PY)							HR (95% CI)
		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)²⁸ 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 patients with NVAF Frailty status was determined using the Johns Hopkins Claims-based Frailty Indicator score (≥0.20 indicating frailty) 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 ischemic stroke, hemorrhagic stroke, or SE. The primary safety outcome was major bleeding. 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 major bleeding (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 major bleeding risk (HR, 1.07; 95% CI, 0.811.32).
Coleman et al (2017)²⁹ 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 ischemic stroke/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 ischemic stroke or ICH (including intracerebral, subarachnoid, and other ICH). The primary safety endpoint was major bleeding. 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 major bleeding. XARELTO significantly reduced ischemic stroke/ICH hazard by 55% (P=0.001) and had no statistically significant effect on major bleeding.
Lip et al (2024)³⁰ Retrospective study using 4 US commercial claims databases (IQVIA LifeLink PharMetrics Plus, Truven MarketScan Commercial Claims and Encounters, OptumInsight, and the Humana Database) between 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
		Major bleeding		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
Abbreviations: AF, atrial fibrillation; BMI, body mass index; , CHADS₂,congestive heart failure, hypertension, age > 75 years, diabetes (all 1 point each); previous stroke (2 points); CHA₂DS₂-VASc ,congestive heart failure, hypertension, age >75 years (doubled), type 2 diabetes mellitus, previous stroke, transient ischemic attack or thromboembolism (doubled), vascular disease, age of 65-75 years, and sex; CI, confidence interval; GI, gastrointestinal; HR, hazard ratio; IPTW, inverse probability of treatment weighting; IR, incidence rate; IS, ischemic stroke; MB, major bleeding; MI, myocardial infarction; NACE, net adverse clinical event; NOAC, non-vitamin K oral anticoagulant; NVAF, non-valvular atrial fibrillation; PSM, propensity score matching; PY, person-years; ref, reference; SE, systemic embolism; TIA, transient ischemic attack^aAn inverse probability of treatment weighting approach, calculated from the propensity score, was utilized to adjust for confounding and balance treatment groups. Valuespresented are after IPTW.^bPropensity score-matched incidence rates and hazard ratios of stroke/SE and major bleeding for NOAC comparisons.^cFrailty 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
Talmor-Barkan et al (2023)³¹ Retrospective, observational study using the Israeli Clalit Health Services (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.	Outcomes^a		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)³² Observational study using The Health Improvement Network (THIN) database (United Kingdome) 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)
		Outcomes	Events/N		Rate per 1000 PY		Events/N	Rate per 1000 PY		aHR (95% CI)
		Primary outcome
		Stroke	57/1839		13.48		56/1839	12.47		0.93 (0.64-1.34)
		Secondary outcomes
		All-cause mortality^b	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)
		Major bleeding 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)³³ 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							HR (95% CI)
		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)
Douros et al (2024)³⁴ Active-comparator, new-user, population-based cohort study using the Clinical Practice Research Datalink [CPRD]) (United Kingdom) and the R´egie de l'assurance maladie du Qu´ebec [RAMQ]) (Quebec Canada) between January 1, 2011 to June 22, 2020 in the CPRD and December 31, 2020 in the RAMQ. Used inverse probability of treatment weighting	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)
			Apixaban^c					XARELTO^c
			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 (reference)
		RAMQ (Quebec)	76/2718				19.35	37/1233			19.46
		aHR (95% CI)	0.92 (0.61-1.37)					1.00 (reference)
		Major Bleeding
		CPRD (UK)	85/1696				53.17	96/1264			66.29
		aHR (95% CI)	0.71 (0.53-0.95)					1.00 (reference)
		RAMQ (Quebec)	283/2718				75.05	147/1233			80.90
		aHR (95% CI)	0.85 (0.70-1.05)					1.00 (reference)
		Secondary outcome (all-cause mortality)³⁵
		CPRD (UK)	127/1696				77.09	98/1264			64.55
		aHR (95% CI)	0.97 (0.75-1.26)					1.00 (reference)
		RAMQ (Quebec)	467/2718				117.12	188/1233			96.95
		aHR (95% CI)	0.99 (0.84-1.18)					1.00 (reference)
Abbreviations: aHR, adjusted hazard ratio; CI, confidence interval; DOAC, direct acting oral anticoagulant; GI, gastrointestinal; ICH, intracranial hemorrhage; ITT, intention-to-treat; MB, major bleeding; MI, myocardial infarction; NVAF, non-valvular atrial fibrillation; PSM, propensity score matching; PY, person-years; ref, reference; RMST (T=3y), restricted mean survival time from baseline to 3 years; SE, systemic embolism; TIA, transient ischemic attack.^aEffectiveness 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. ^bIn 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.^cInverse probability of treatment weighting (IPTW) was applied based on propensity scores to adjust for potential confounders and covariates.

LITERATURE SEARCH

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, DERWENT^® (and/or other resources, including internal/external databases) was conducted on 29 July 2024.

References

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