Proven once-daily* stroke risk reduction1,2

Demonstrated clinical outcomes in an obesity subgroup and consistent real-world evidence in patients who have NVAF and obesity3,4

*Taken with evening meal.

NVAF = nonvalvular atrial fibrillation; SE = systemic embolism.

Updated AF Guideline

Guideline for atrial fibrillation (AF)

2023 ACC/AHA/ACCP/HRS guideline recommends XARELTO®

as an option for eligible patients with AF,† with no age limitations for older adults5

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†XARELTO® is indicated to reduce the risk of stroke and systemic embolism in adult patients with nonvalvular atrial fibrillation. The use of XARELTO® is not recommended in patients with prosthetic heart valves. While no longer using the "valvular" and "nonvalvular" classifications of AF and concluding that those terms are obsolete, the 2023 Guideline for the Diagnosis and Management of Atrial Fibrillation notes that DOACs are currently recommended as first-line therapy over warfarin in patients with AF (except those with moderate to severe mitral stenosis or mechanical heart valve recipients).

ACC = American College of Cardiology; ACCP = American College of Clinical Pharmacy; AF = atrial fibrillation; AHA = American Heart Association; DOAC = direct oral anticoagulant; HRS = Heart Rhythm Society; NVAF = nonvalvular atrial fibrillation.

Efficacy in ROCKET AF

Effectively reduced risk of stroke/SE vs warfarin1

Noninferior stroke/SE risk reduction in ITT population (N=14,171)*†

Efficacy in ROCKET AF: noninferior stroke/systemic embolism (SE) risk reduction in intent-to-treat (ITT) population
  • Stroke or SE event rates per 100 patient-years were 2.4 in patients taking warfarin and 2.1 in patients taking XARELTO®
  • XARELTO® demonstrated noninferiority vs warfarin, but superiority was not established. There are limited data on the relative effectiveness of XARELTO® and warfarin in reducing the risk of stroke and SE when warfarin therapy is well controlled

Stroke risk reduction in patients taking ≥1 dose (N=14,143)1¶

Efficacy in ROCKET AF: stroke risk reduction in patients taking >=1 dose
  • Stroke or SE event rates per 100 patient-years were 2.2 in patients taking warfarin and 1.7 in patients taking XARELTO®1
  • A superiority analysis was conducted in the safety population during treatment (safety, as-treated population), which included patients who received at least 1 dose of study drug and were followed for events, while they were receiving treatment or within 2 days after discontinuation1
  • XARELTO® demonstrated noninferiority versus warfarin, but superiority was seen in the safety, as-treated population. There are limited data on the relative effectiveness of XARELTO® and warfarin in reducing the risk of stroke and SE when warfarin therapy is well controlled1
  • The conventional method for establishing superiority is in the ITT population using data from all patients who were randomized to treatment, and this analysis did not support the superiority of XARELTO® to warfarin6

*Primary efficacy endpoint data are shown for all randomized patients followed to site notification that the study would end (ITT population).

†Superiority was achieved in the safety, as-treated population in a secondary analysis of patients taking at least 1 dose of XARELTO®. The ITT population demonstrated noninferiority.

‡A 12% RRR in stroke or SE was observed in patients receiving XARELTO® (n=269) vs warfarin (n=306) (HR=0.88 (95% CI: 0.74-1.03); P<0.001 for noninferiority): RRR was calculated using 1 minus the HR.

§Not statistically significant.

IIARR = 2.4% - 2.1% = 0.3%.

¶Superiority was achieved in the safety, as-treated population in a secondary analysis of patients taking at least 1 dose of XARELTO®. The ITT population demonstrated noninferiority.

#A 21% RRR in stroke or SE was observed in patients receiving XARELTO® (n=189) vs warfarin (n=243); HR=0.79 (95% CI: 0.65-0.95); P=0.02; RRR was calculated using 1 minus the HR.

**ARR = 2.2% - 1.7% = 0.5%.

AF = atrial fibrillation; ARR = absolute risk reduction; CI = confidence interval; HR = hazard ratio; ITT = intent-to-treat; RRR = relative risk reduction; SE = systemic embolism.

Efficacy in ROCKET AF obesity subgroup

Stroke/SE events with XARELTO® and warfarin in NVAF
patients with obesity vs patients with normal weight3

A ROCKET AF subgroup analysis of patients with obesity vs patients with normal weight (n=8495)

Efficacy in ROCKET AF obesity subgroup: stroke/systemic embolism (SE) events with XARELTO® (rivaroxaban) and Warfarin in nonvalvular atrial fibrillation (NVAF) patients with obesity versus patients with normal weight
  • Stroke and SE event rates per 100 patient-years were 2.93 in the normal-weight group (reference group), 2.28 in the overweight group (adjusted HR=0.81; 95% CI: 0.66-0.99), and 1.88 in the obese group (adjusted HR=0.69; 95% CI: 0.55-0.86)3
  • 37% of patients in the ROCKET AF trial had obesity and 13% had a BMI >35 kg/m2
  • Patients with a BMI ≥30 kg/m2 had a mean CHADS2 score of 3.5 and a median age of 70 years3,7

AF = atrial fibrillation; BMI = body mass index; CHADS₂ = congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke (double weight); CI = confidence interval; HR = hazard ratio; NVAF = nonvalvular atrial fibrillation; SE = systemic embolism.

Real-world evidence

Effectiveness in patients with NVAF and obesity*

Rates of stroke/SE across BMI classes4

Rates of stroke/SE vs warfarin†

Effectiveness in patients with nonvalvular atrial fibrillation (NVAF) and obesity: rates of stroke/systemic embolism (SE) across BMI classes

*Patients were identified as obese based on a BMI measurement of ≥30 kg/m2.

†Due to differences in study design, patient populations, definitions of outcomes, and data collection methods, the results of real-world studies are not intended for direct comparisons with clinical trials.

‡RRR = (1 - 0.83) x 100% = 17%.

§ARR = 1.88% - 1.20% = 0.68%.

ARR = absolute risk reduction; BMI = body mass index; CI = confidence interval; EHR = electronic health record; HR = hazard ratio; INR = international normalized ratio; ITT = intent-to-treat; NVAF = nonvalvular atrial fibrillation; OAC = oral anticoagulant; RRR = relative risk reduction; RWE = real-world evidence; SE = systemic embolism; US = United States.

Real-world evidence

One of the longest average follow-up periods comparing XARELTO® and Eliquis®* in patients with NVAF (average follow-up period of >2 years)8,9†

Effectiveness outcomes

XARELTO® vs Eliquis®: Differences seen in ischemic stroke8‡

XARELTO® (rivaroxaban) vs Eliquis®: differences seen in ischemic stroke

XARELTO® was associated with an ischemic stroke rate of 49.3 vs 55.8 for Eliquis® per 1000 person-years

Note: Due to differences in study design, patient populations, definitions of outcomes, and data collection methods, the results of real-world studies are not intended for direct comparisons with clinical trials.

Talmor-Barkan et al: a head-to-head nationwide (in Israel), retrospective, observational study of DOAC treatment in NVAF, published in the European Heart Journal - Cardiovascular Pharmacotherapy and not funded by industry

*Eliquis® (apixaban) is a registered trademark of Bristol-Myers Squibb Company.

†Based on the total person-years and matched number of patients, the approximate mean follow-up period per at-risk patient was calculated as >2 years.

‡The order of the pairwise comparisons was not prespecified, and no adjustments for multiplicity were made.

§8% RRR was calculated using 1 minus the HR.

II6.5 ARR was calculated as 55.8 - 49.3.

¶Only the largest cohort comparison group is shown. The smaller cohort comparisons between apixaban and dabigatran and between rivaroxaban and dabigatran can be reviewed in the study publication.

CI = confidence interval; HR = hazard ratio; RWE = real-world evidence.

Safety in ROCKET AF

Proven safety profile vs warfarin10

Bleeding events (on treatment plus 2 days) vs warfarin*
Clinical endpointXARELTO® %/Yr | (n/N)Warfarin %/Yr | (n/N)HR (95% CI)
Major bleeding*3.6(395/7111)3.5(386/7125)1.04(0.90-1.20)
ICH†0.5(55/7111)0.7(84/7125)0.67(0.47-0.93)
Hemorrhagic stroke‡0.3(36/7111)0.5(58/7125)0.63(0.42-0.96)
Other ICH0.2(19/7111)0.2(26/7125)0.74(0.41-1.34)
GI bleeding§2.0(221/7111)1.2(140/7125)1.61(1.30-1.99)
Fatal bleedingII0.2(27/7111)0.5(55/7125)0.50(0.31-0.79)
ICH0.2(24/7111)0.4(42/7125)0.58(0.35-0.96)
Non-intracranial0.0(3/7111)0.1(13/7125)0.23(0.07-0.32)

*Major bleeding was defined as clinically overt bleeding associated with hemoglobin decrease ≥2 g/dL, transfusion of ≥2 units of packed red blood cells or whole blood, bleeding at a critical site, or with fatal outcomes (ISTH criteria).11

†Intracranial bleeding events included intraparenchymal, intraventricular, subdural, subarachnoid, and/or epidural hematoma.

‡Hemorrhagic stroke in this table specifically refers to nontraumatic intraparenchymal and/or intraventricular hematoma in patients on treatment plus 2 days.

§GI bleeding events included upper GI, lower GI, and rectal bleeding.

IIFatal bleeding is adjudicated death with the primary cause of death from bleeding.

GI = gastrointestinal; ICH = intracranial hemorrhage; ISTH = International Society on Thrombosis and Haemostasis.

Safety in ROCKET AF obesity subgroup

Outcomes for XARELTO® vs warfarin across BMI subgroups in ROCKET AF ITT population3

XARELTO® vs warfarin by BMI subgroups in the ITT population
Major or NMCRBBMI weightXARELTO®WarfarinHR (95% CI)
Normal 18.50-24.99 kg/m20.97 (0.84-1.13)
Overweight 25.00-29.99 kg/m21.18 (1.05-1.33)
Obese ≥30.00 kg/m20.93 (0.82-1.04)
Major BleedingNormal 18.50-24.99 kg/m20.92 (0.69-1.24)
Overweight 25.00-29.99 kg/m21.05 (0.84-1.31)
Obese ≥30.00 kg/m21.15 (0.91-1.45)

AF = atrial fibrillation; BMI = body mass index; CDC = Centers for Disease Control and Prevention; HR = hazard ratio; ITT = intent-to-treat; NMCRB = nonmajor clinically relevant bleeding.

Real-world evidence

Patients with NVAF and obesity*

Rates of major bleeding† across BMI classes4

Rates of major bleeding vs warfarin‡

Graph of patients with nonvalvular atrial fibrillation (NVAF) and obesity: rates of major bleeding across BMI classesGraph of patients with nonvalvular atrial fibrillation (NVAF) and obesity: rates of major bleeding across BMI classes

Study limitations:

  • An EHR entry indicating initiation/use of an OAC does not guarantee a patient took it or allow for assessment of adherence or persistence, due to the lack of prescription claims data. Therefore, the analyses performed used an ITT approach
  • Nonrandomized studies can be impacted by confounding, misclassification, and sampling biases
  • Study findings were most generalizable to US population given the database used
  • Time in therapeutic INR was not calculated for warfarin patients
  • Additional analyses based on dose were not done due to the lack of INR data/therapeutic target range and the small proportion of rivaroxaban patients that were prescribed a low dose
  • The database did not cover all institutions and therefore follow-up events may have been missed
  • Investigation of the potential impact of socioeconomic status and patients’ actual incomes on study outcomes was not possible
  • Reliable mortality data was not available

*Patients were identified as having obesity based on a BMI measurement of >30 kg/m2.

†Major bleeding was defined by the validated Cunningham algorithm.

‡Due to differences in study design, patient populations, definitions of outcomes, and data collection methods, the results of real-world studies are not intended for direct comparisons with clinical trials.

§RRR = (1 - 0.82) x 100% = 18%.

IIARR = 3.88% - 2.46% = 1.42%.

ARR = absolute risk reduction; BMI = body mass index; CI = confidence interval; EHR = electronic health record; HR = hazard ratio; INR = international normalized ratio; ITT = intent-to-treat; NVAF = nonvalvular atrial fibrillation; OAC = oral anticoagulant; RRR = relative risk reduction; RWE = real-world evidence; US = United States.

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One of the longest average follow-up periods comparing XARELTO® and Eliquis® in patients with NVAF (average follow-up period of >2 years)8,9*

Safety outcomes

XARELTO® vs Eliquis®: Differences seen in bleeding risks8†
Outcomes‡Event Rate (per 1000 person-years)Favors XARELTO®Favors Eliquis®HR (95% CI)
Overall bleeding XARELTO®: n=15,654 Eliquis®: n=15,631No differences were observed in overall bleeding rates1.02 (0.92-1.13)
Intracranial hemorrhage XARELTO®: n=15,654 Eliquis®: n=15,633XARELTO® was associated with an ICH rate of 9.4 vs 11.6 for Eliquis® per 1000 person-years0.86 (0.74-1.00)
Gastrointestinal bleeding XARELTO®: n=15,668 Eliquis®: n=15,667XARELTO® was associated with a GI bleeding rate of 9.5 vs 7.9 for Eliquis® per 1000 person-years1.22 (1.03-1.44)
Bleeding, other XARELTO®: n=15,668 Eliquis®: n=15,667No differences were observed in other bleeding rates1.18 (0.94-1.48)

*Based on the total person-years and matched number of patients, the approximate mean follow-up period per at-risk patient was calculated as >2 years.

†The order of the pairwise comparisons was not prespecified, and no adjustments for multiplicity were made.

‡Only the largest cohort comparison group is shown. The smaller cohort comparisons between apixaban and dabigatran and between rivaroxaban and dabigatran can be reviewed in the study publication.

CI = confidence interval; GI = gastrointestinal; HR = hazard ratio; ICH = intracranial hemorrhage; RWE = real-world evidence.

Dosing

Reducing stroke/SE risk

XARELTO® (rivaroxaban) tablet 20 mg

20 mg

Taken once daily with the evening meal in patients with
CrCl >50 mL/min

OR

XARELTO® (rivaroxaban) tablet 15 mg

15 mg

Taken once daily with the evening meal in patients with
CrCl ≤50 mL/min

Tablets shown not actual size.

Renal dosing
considerations

Periodically assess renal function as clinically indicated (ie, more frequently in situations in which renal function may decline) and adjust therapy accordingly. Consider dose adjustment or discontinuation of XARELTO® in patients who develop acute renal failure while on XARELTO®.

 

Patients with CrCl <30 mL/min were not studied, but administration of XARELTO® is expected to result in serum concentrations of rivaroxaban similar to those in patients with moderate renal impairment (CrCl 30 to <50 mL/min).

See section 8.6 of the Prescribing Information for additional information

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Once-daily XARELTO® (rivaroxaban): 365 fewer doses over 1 year
Once-daily* XARELTO® carries a lower pill burden than Eliquis®10,12
*Taken with the evening meal.

CrCl = creatinine clearance; NVAF = nonvalvular atrial fibrillation; SE = systemic embolism.

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REFERENCES: 1. Patel MR, Mahaffey KW, Garg J, et al; and the ROCKET AF Steering Committee, ROCKET AF Investigators. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365(10):883-891. 2. Kubitza D, Becka M, Voith B, Zuehlsdorf M, Wensing G. Safety, pharmacodynamics, and pharmacokinetics of single doses of BAY 59-7939, an oral, direct factor Xa inhibitor. Clin Pharmacol Ther. 2005;78(4):412-421. 3. Balla SR, Cyr DD, Lokhnygina Y, et al. Relation of risk of stroke in patients with atrial fibrillation to body mass index (from patients treated with rivaroxaban and warfarin in the rivaroxaban once daily oral direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and embolism trial in atrial fibrillation trial). Am J Cardiol. 2017;119(12):1989-1996. 4. Costa OS, Beyer-Westendorf J, Ashton V, et al. Effectiveness and safety of rivaroxaban versus warfarin in obese nonvalvular atrial fibrillation patients: analysis of electronic health record data. Curr Med Res Opin. 2020;36(7):1081-1088. 5. Joglar JA, Chung MK, Armbruster AL, et al. 2023 ACC/AHA/ACCP/HRS Guideline for the diagnosis and management of atrial fibrillation: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2024;83(1):109-279. 6. Lesaffre E. Superiority, equivalence, and non-inferiority trials. Bull NYU Hosp Jt Dis. 2008;66(2):150-154.
7. Data on file. Janssen Pharmaceuticals, Inc. 8. Talmor-Barkan, Yacovzada N-S, Rossman H, et al. Head-to-head efficacy and safety of rivaroxaban, apixaban, and dabigatran in an observational nationwide targeted trial. J Eur Heart Cardiovasc Pharmacother. 2022;9(1):26-37. 9. Data on file. Janssen Pharmaceuticals, Inc. 10. XARELTO® [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals, Inc. 11. Online supplement to: Patel MR, Mahaffey KW, Garg J; ROCKET AF Investigators. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365(10):883-891. 12. Eliquis® [prescribing information]. Princeton, NJ and New York, NY: Bristol-Myers Squibb Company and Pfizer, Inc.; 2021.