Summary

• Wang et al (2024)¹ conducted a retrospective study comparing the safety and efficacy of XARELTO and edoxaban in patients with lower extremity deep vein thrombosis (DVT). Compared with the edoxaban group, the XARELTO group showed a significant reduction in thrombosis recurrence (P<0.05) as well as lower mortality rates (P<0.05). There was no significant difference in incidence of major bleeding at various sites between the treatment groups (P>0.05).
• Lau et al (2022)² conducted a comparative multinational population-based cohort study in routine clinical practice between direct oral anticoagulants (DOACs [apixaban, dabigatran, edoxaban, and XARELTO]). Data specific to XARELTO vs edoxaban in the United States (US) was available for composite of ischemic stroke and systemic embolism, intracranial hemorrhage (ICH), and gastrointestinal (GI) bleeding in patients diagnosed with atrial fibrillation (AF).
• Lee et al (2019)³ compared the efficacy and safety of XARELTO and edoxaban in patients with nonvalvular atrial fibrillation using data from the Korean National Health Insurance Service. In both standard and reduced dose matching cohorts, XARELTO and edoxaban were associated with similar outcomes for ischemic stroke, ICH, hospitalization for GI bleeding and major bleeding, all-cause death, and the composite outcome (ischemic stroke + ICH + all-cause death).
• Additional citations (eg, indirect comparisons) identified during a literature search are included in the REFERENCES section for your review.^4-17

CLINICAL STUDIES

Deep Vein Thrombosis

Wang et al (2024)¹ conducted a retrospective study that evaluated the safety and efficacy of XARELTO and edoxaban in adult patients with lower extremity DVT.

Study Design/Methods

• Patients subjected to treatment with DOACs for DVT at a hospital were included.
• Primary outcome: mortality rates, incidence of bleeding (defined using International Society of Thrombosis and Hemostasis criteria), and recurrence of thrombosis.
• In the XARELTO group, patients were treated with a standard initial dose of XARELTO 15 mg twice daily for the first 21 days, followed by 20 mg once daily for extended treatment. In the edoxaban group, patients were treated with a standard initial dose of edoxaban 60 mg once daily after initial treatment with a parenteral anticoagulant administered for at least 5 days.

Results

• A total of 406 patients were included in the study.
  • XARELTO group (n=199): age range, 45-66 years; 27.1% were male; and 7.5% had a history of venous thromboembolism (VTE).
  • Edoxaban group (n=207): age range, 59-68 years; 26.6% were male; and 4.8% had a history of VTE.
• Compared with the edoxaban group, the XARELTO group showed a statistically significant reduction in thrombosis recurrence (P<0.05).
• There was no significant difference in incidence of major bleeding at various sites between the treatment groups (P>0.05).
  • After a follow-up of 14 days, the incidence of major bleeding events was 7.0% in the XARELTO group and 10.6% in the edoxaban group.
• The mortality rates were significantly higher in the edoxaban group than in the XARELTO group (P<0.05).

Nonvalvular Atrial Fibrillation

Lau et al (2022)² conducted a comparative multinational population-based cohort study in routine clinical practice between DOACs (apixaban, dabigatran, edoxaban, and XARELTO).

Study Design/Methods

• Patient records from 5 electronic health databases across 4 countries (France, Germany, United Kingdom, and the US) we included in the study.
• The study included patients newly prescribed a DOAC for AF, aged ≥ 18 years-old, and DOAC naïve from 2010 through 2019.
• Patients were followed from start date until the occurrence of the study outcome, discontinuation of treatment (90-day gaps between consecutive prescriptions with the date of discontinuation being the end date of the last prescription), switching to another anticoagulant (apixaban, dabigatran, edoxaban, XARLETO, or warfarin), death, or end of the study.
• Outcomes included: a composite of ischemic stroke and systemic embolism, ICH, GI bleeding, and all-cause mortality.
• Propensity score modeling was utilized to compare patients who differed in treatment but were similar in characteristics.

Results

• Across the 5 electronic health databases, a total of 527,226 patients met the inclusion criteria (edoxaban, n=12,722; and XARELTO, n=172,176).
  • The results presented will focus on XARELTO vs edoxaban from the US and will include US Ambulatory Electronic Medical Records (US AMBEMR). XARELTO vs edoxaban comparison did not meet the pre-specified sample size requirements of      n≥1000 in each group for the US Hospital Charge Data Master (US HOSPITAL) database.¹⁸
• Please see Table: XARELTO vs Edoxaban – US Cohort size, Outcome events, and Hazard Ratios for Propensity Score-Stratified, On-Treatment Approach (US AMBEMR).¹⁸

• For US AMBEMR, all-cause mortality was not estimated as date of death was not available.¹⁸

Lee et al (2019)³ compared the efficacy and safety of XARELTO and edoxaban in patients with nonvalvular atrial fibrillation using data from the Korean National Health Insurance Service.

Study Design/Methods

• Patients who were diagnosed with atrial fibrillation between January 2013 and December 2016 were identified.
• Six clinical outcomes were identified during the study period (January 2014 to December 2016): ischemic stroke, ICH, hospitalization for GI bleeding, hospitalization for major bleeding, all-cause death, and composite outcome of ischemic stroke + ICH + all-cause death.
• In both XARELTO and edoxaban groups, predefined dose reduction criteria were used, because the baseline characteristics of patients taking a reduced dose (XARELTO 15/10 mg and edoxaban 30 mg) might be different from those of patients taking a standard dose (XARELTO 20 mg and edoxaban 60 mg). For separate analysis by dose regimens, both standard (XARELTO 20 mg and edoxaban 60 mg) and reduced dose (XARELTO 15/10 mg and edoxaban 30 mg) groups were matched separately based on propensity scores.
• Hazard ratios (HRs) for the 6 clinical outcomes were analyzed using Cox regression analysis with XARELTO as the reference.
• Subgroup analyses were performed based on patients’ age (<65 years, 65-74 years, and ≥75 years), sex, estimated stroke risk (CHA₂DS₂-VASc scores: 0-2 and ≥3), and renal function (creatinine clearance [CrCl]: ≤50 mL/min and >50 mL/min).
• Subgroup analysis was also performed by patients’ body weight (≤60 kg and >60 kg).
• Additionally, patients with CrCl >95 mL/min were analyzed separately to assess the efficacy and safety of XARELTO and edoxaban in patients with “high normal” renal function.
• A sensitivity analysis was conducted with restriction of the follow-up duration to 6 months because of the shorter follow-up duration of the edoxaban group.
• Another sensitivity analysis was performed among patients who were only enrolled after February 2016 (when edoxaban was introduced into the market).

Results

• After 3:1 propensity score matching, 12,369 XARELTO-treated patients were matched to 4123 edoxaban-treated patients.
• Baseline characteristics were balanced between the 2 groups (mean age, 71±10 years; mean CHA₂DS₂-VASc score, 3.3±1.6; 56% of patients received a reduced dose).
• Among patients with available CrCl value (80% of the population in each group), 654 patients (5%) had moderate renal dysfunction (CrCl ≤50 mL/min).
• The median follow-up duration was 0.8 years (interquartile range [IQR] 0.4-0.9 years) in the XARELTO cohort and 0.3 years (IQR 0.1-0.5 years) in the edoxaban cohort (P<0.001).
• No significant differences were found between edoxaban and XARELTO for all 6 clinical outcomes.
• Detailed data for the number of events and crude incidence rates according to treatment are summarized in Table: Number of Patients with Event and Crude Incidence Rates of 6 Study Outcomes.
• In sensitivity analyses for adjusting the differences in follow-up duration to 6 months, HR trends for all clinical outcomes were similar to the main results.
  • When comparing those with the same period of enrollment, edoxaban showed lower risks of hospitalization for GI bleeding (HR 0.698, 95% confidence interval [CI] 0.546-0.880; P=0.002), hospitalization for major bleeding (HR 0.628, 95% CI 0.384-0.977; P=0.038), all-cause death (HR 0.663, 95% CI 0.443-0.957; P=0.027) and composite outcomes (HR 0.766, 95% CI 0.628-0.927; P=0.005) compared to XARELTO.
• HRs of edoxaban compared to XARELTO were generally consistent in both standard and reduced dose regimens. No significant interaction was found between treatment and dose regimens in all 6 clinical outcomes. Detailed data for the number of events and crude incidence rates according to treatment are summarized in Table: Number of Patients with Event and Crude Incidence Rates of 6 Study Outcomes.
• HRs were generally consistent among subgroups.
• XARELTO and edoxaban showed generally comparable outcomes in both groups stratified by renal function.
  • Although there was no significant interaction between treatment and renal function, edoxaban was associated with lower risk of hospitalization for GI bleeding compared to XARELTO in patients with CrCl >50 mL/min (HR 0.455, 95% CI 0.202-0.887; P=0.034).
• Edoxaban showed better composite outcome than XARELTO in patients with body weight >60 kg, of borderline significance (HR 0.672, 95% CI 0.434-0.998; P=0.049, P for interaction=0.058).

LITERATURE SEARCH

A literature search of MEDLINE^®,EMBASE^®, BIOSIS Previews^®, DERWENT^® (and/or other resources, including internal/external databases) pertaining to this topic was conducted on 08 October 2024.