XARELTO - Real-world Data of Rivaroxaban vs Apixaban in Treatment of Venous Thromboembolism

SUMMARY

• Published studies on real-world data of apixaban vs XARELTO for venous thromboembolism (VTE) treatment are summarized in the following sections:
• Effectiveness and Safety:
  • In a retrospective, observational cohort study performed using the TriNetX Research Network to evaluate treatment effects and the risk-benefit profile of XARELTO and apixaban in patients with acute VTE, statistically significant differences in recurrent VTE were observed between the treatment groups at 6 months, 1 year, and 2 years.¹
  • In a pragmatic, international study with a prospective, randomized, open-label, blinded endpoint (PROBE) design, a significant difference in clinically relevant bleeding was observed between the apixaban and XARELTO groups.²
  • A parallel-group, new-user cohort study performed using 3 United States (US) healthcare claims databases; a registry-based prospective multicenter study performed using data from the SAKURA PE/DVT Registry; and an observational, register-based cohort study of Swedish patients evaluated the effectiveness and safety of apixaban and XARELTO in patients with VTE.^3-5
  • In a systematic review and meta-analysis comparing apixaban and XARELTO in real-world settings, no significant difference was reported in recurrent VTE events between the apixaban and XARELTO groups. Additionally, no difference was found between the 2 groups for events of major, intracranial, gastrointestinal (GI), and hospitalized bleeding and death. However, apixaban users reported a 46% lower risk of minor bleeding than XARELTO users.^6,7
  • Four retrospective cohort analyses were conducted to evaluate the effectiveness and safety of apixaban and XARELTO in newly diagnosed patients with VTE.^8-11 In a separate cohort study, the safety and efficacy of apixaban and XARELTO were assessed in patients with a prior diagnosis of either deep vein thrombosis (DVT) or pulmonary embolism (PE) on or before the anticoagulation start date.¹²
  • In another systematic review of studies comparing apixaban with XARELTO in real-world settings, no difference in VTE recurrence was identified between the 2 treatment groups. Clinically relevant major bleeding occurred in fewer patients in the apixaban group than in the XARELTO group.¹³ A prospective analysis evaluated the efficacy and safety of XARELTO vs apixaban in the treatment of patients with acute VTE.¹⁴
• Specific Populations:
  • Several studies evaluated the efficacy and safety of apixaban and XARELTO for the treatment of VTE in specific patient populations, including patients with active solid tumors, patients with GI cancers, patients with cancer-associated VTE, patients with pancreatic cancer, patients with colorectal cancer, patients with gastric cancer, women of reproductive age, patients with chronic liver disease, Asian patients, young adults, fragile patients, and patients with extremes of body weight.^15-29
• Bleeding Events and Healthcare Utilization:
  • Additional studies summarized below include those analyzing bleeding events^30-32 and a study reporting the impact of anticoagulant choice on healthcare resource utilization.^33-36
• Additional citations identified during a literature search are included in the REFERENCES section for your review.^37-51

CLINICAL DATA

Real-world Evidence

Effectiveness and Safety

Ahmed et al (2026)¹ conducted a retrospective, observational cohort study using the TriNetX Research Network, which contains deidentified electronic medical records, to evaluate treatment effects and risk-benefit profiles of XARELTO and apixaban in patients with acute VTE. A data analysis was performed on April 19, 2026. The study included adults aged ≥18 years with acute VTE, including PE and acute embolism or DVT of the lower or upper extremities.

• The primary outcome was recurrent VTE, defined as a composite of PE and DVT. Secondary outcomes comprised all-cause mortality, composite major bleeding, major bleeding, nonmajor bleeding, GI bleeding, and intracerebral hemorrhage. See Table: Clinical Outcomes at Multiple Follow-up Intervals in the Overall Propensity Score-Matched Acute VTE Population.
• A total of 35,589 patients were identified before propensity score matching, including 26,796 patients receiving apixaban and 8793 patients receiving XARELTO. After propensity score matching, 8247 patients remained in each treatment group.

• Results of subgroup analyses stratified by active cancer and the obesity status are presented in the publication.
• A sensitivity analysis for recurrent VTE showed a recurrence rate of 49.61% in the apixaban group and 49.59% in the XARELTO group at 3 months, with a hazard ratio (HR) of 1.01 (95% confidence interval [CI], 0.97-1.05; log-rank P=0.682).
  • Given the high recurrence rate observed at 3 months, an additional analysis was performed to evaluate events occurring between day 1 and day 30; it revealed a recurrence rate of 42.83% in the apixaban group and 43.3% in the XARELTO group, with an HR of 0.99 (95% CI, 0.95-1.04; log-rank P=0.771).

Castellucci et al (2026)² conducted the Comparison of Bleeding Risk between Rivaroxaban and Apixaban (COBRRA) trial, a pragmatic, international study with a PROBE design. Adults (≥18 years) with symptomatic acute VTE, including acute proximal lower-limb DVT or segmental or more proximal PE, were eligible for enrollment. The study aimed to determine whether apixaban was superior to XARELTO with respect to safety in patients with acute VTE.

• Participants were randomized to receive XARELTO 15 mg twice daily for 21 days followed by 20 mg daily or apixaban 10 mg twice daily for 7 days followed by 5 mg twice daily.
• The primary outcome was clinically relevant bleeding, defined as a composite of major bleeding or clinically relevant nonmajor bleeding. Secondary outcomes included the individual components of the primary outcome, recurrent symptomatic VTE (a composite of recurrent DVT or recurrent PE), death from bleeding, death from recurrent VTE, death from any cause, and medication adherence, which was assessed at each follow-up visit. See Table: Clinical Outcomes During the Trial Period.
• Between December 13, 2017, and January 23, 2025, 2760 patients underwent randomization. In the intention-to-treat analysis, 1355 patients received XARELTO and 1345 patients received apixaban.

• Findings for clinically relevant bleeding were generally consistent across the prespecified subgroups.
• In a sensitivity analysis performed using a generalized linear mixed-effects model, the adjusted marginal relative risk was 0.45 (95% CI, 0.32-0.64) for apixaban vs XARELTO.
• Among patients receiving apixaban, all 5 patients with major bleeding had a decrease in hemoglobin level or blood transfusion. In the XARELTO group, 28 patients with major bleeding had a decrease in hemoglobin level or blood transfusion, while 4 patients experienced bleeding in a critical area or organ.
• No deaths due to bleeding occurred in either treatment group.
• The most common clinically relevant nonmajor bleeding events were vaginal bleeding (2.7%) and GI bleeding (0.6%) in the apixaban group and vaginal bleeding (3.8%), hematuria (1.3%), and GI bleeding (1%) in the XARELTO group.
• No deaths attributed to recurrent VTE occurred in either treatment group.
• Complete medication adherence was reported by 75.1% of patients receiving XARELTO and 65.7% of patients receiving apixaban.
• Serious adverse events unrelated to bleeding or venous thrombosis occurred in 30 patients (2.2%) in the XARELTO group and 36 patients (2.7%) in the apixaban group.

Bea et al (2025)³ conducted a parallel-group, new-user cohort study using 3 US healthcare claims databases: fee-for-service Medicare claims collected by the Centers for Medicare & Medicaid Services (2016-2020), Merative MarketScan (2016-2022), and Optum deidentified Clinformatics Data Mart (2016-2024). The study included adults aged ≥18 years (≥65 years for Medicare) who were initiated on oral anticoagulant therapy within 30 days of discharge for VTE and had at least 365 days of continuous insurance coverage. The objective was to compare the effectiveness and safety of XARELTO, apixaban, and warfarin among individuals with VTE using longitudinal, deidentified administrative healthcare data from publicly and commercially insured US populations.

• The primary effectiveness outcome was hospitalization for recurrent DVT or PE. The primary safety outcome was hospitalization for major bleeding, including intracranial, GI, or other major bleeding events. Secondary outcomes included all-cause mortality and a composite outcome comprising hospitalization for recurrent VTE, hospitalization for major bleeding, and all-cause mortality.
• A total of 163,593 eligible patients were initiated on 1 of the study oral anticoagulants within 30 days of VTE discharge between 2017 and 2024. Of these, 25.7% received XARELTO and 58.5% received apixaban.
• Over a median (interquartile range [IQR]) follow-up of 169 (66-339) days, 3270 hospitalizations for recurrent VTE were identified. Over a median (IQR) follow-up of 169 (67-339) days, 4229 hospitalizations for major bleeding were identified. See Table: Comparative Effectiveness and Safety of XARELTO and Apixaban in Patients With VTE.

• Sensitivity analyses, performed using an intention-to-treat approach, a continuous exposure definition allowing a gap of up to 30 days between refills, or the exclusion of patients with a prior outpatient VTE diagnosis, yielded findings consistent with those of the primary analyses.
  • Using a restricted definition of major bleeding, weighted HR for apixaban vs XARELTO was 0.63 (95% CI, 0.57-0.7).
• Subgroup analyses:
  • Bleeding findings were consistent across sex and frailty subgroups.
  • VTE findings were generally consistent across the assessed subgroups.
  • However, for bleeding, the findings for XARELTO vs warfarin were more pronounced among patients aged <65 years (HR, 0.61; 95% CI, 0.43-0.87) than among those aged ≥65 years (HR, 1.05; 95% CI, 0.95-1.15).
  • In subgroup analyses of all-cause mortality, apixaban and XARELTO were associated with higher mortality compared with warfarin among patients with active cancer.
  • Among patients without cancer, no differences were observed across the 3 treatments.
  • In the prefrail subgroup, mortality was higher with apixaban than with XARELTO.

Migita et al (2025)⁴ conducted a registry-based, prospective, multicenter study using data from the SAKURA PE/DVT REGISTRY (July 2021 to December 2022) to describe the characteristics of patients with VTE treated with individual direct oral anticoagulants (DOACs; XARELTO, apixaban, and edoxaban), assess the incidence of clinical events, and evaluate the effect of DOAC therapy on pulmonary artery (PA) thrombus regression. The secondary objective was to determine whether PA thrombus regression monitoring using early computed tomography (CT), performed 2 weeks after the initiation of intensive XARELTO therapy, could identify patients with significant PA thrombus regression. Eligible patients had acute symptomatic or asymptomatic PE, DVT, or both and received a DOAC for the treatment and prevention of VTE.

• The primary endpoint was the thrombus regression rate in the intrapulmonary artery assessed by early contrast-enhanced CT. Secondary endpoints included clinical events occurring during the follow-up period, comprising recurrent or aggravated symptomatic VTE, PE, DVT, bleeding, vascular events (acute coronary syndrome or ischemic stroke), death from any cause, cancer-related death, and composite clinical events.
• The study included 175 patients with VTE; of these, 111 (63.4%) received XARELTO, 41 (23.4%) received apixaban, and 23 (13.1%) received edoxaban.
• Thrombus regression rate:
  • The median (IQR) interval between acute- and recovery-phase CT scans was 13 (11-14) days, with no significant difference among the XARELTO, apixaban, and edoxaban groups (13 [11-14], 13 [10-14], and 14 [12-15] pg/mL, respectively; P=0.10).
  • Among 153 patients with PE, thrombus measurement was not possible in 9 patients because of poor image quality. PA thrombus analysis using CT was possible in 144 patients during the acute phase and in 142 patients during the recovery phase. Two patients did not undergo recovery-phase CT due to exacerbation of the underlying disease (n=1) and due to an allergy to contrast agents (n=1).
  • A significant difference in the median (IQR) acute-phase PA thrombus amount was observed among the XARELTO, apixaban, and edoxaban groups (6.7 [2.1-15.4], 2.1 [0.7-5.1], and 1.7 [0.4-14] mm³, respectively; P<0.001).
  • The median (IQR) acute-phase intrapulmonary arterial thrombus volume was higher in the XARELTO vs apixaban group (6.7 [2.1-15.4] vs 2.1 [0.7-5.1] mm³; P=0.002) and tended to be higher in the XARELTO vs edoxaban group (6.7 [2.1-15.4] vs 1.7 [0.4-14] mm³; P=0.08).
  • In contrast, no difference in the median (IQR) thrombus regression rate was observed among the XARELTO, apixaban, and edoxaban groups (88.6% [76-99.5], 94.2% [73.9-100], and 94.4% [70-100], respectively; P=0.38).
  • The median thrombus regression rate after approximately 2 weeks of treatment was 89.9%.
• Relationship between clinical events and DOAC therapy:
  • Patients with VTE were followed until December 2023; the median follow-up duration was 13.5 months (IQR, 11.7-17.9).
  • Clinical events in patients with VTE who were treated with DOACs are summarized in Table: Clinical Outcomes of Stratified Patients With VTE by DOACs.
  • A significant difference in major bleeding was observed between the XARELTO and apixaban groups (log-rank P=0.019). Among the 6 patients in the apixaban group who experienced major bleeding, 3 patients experienced an event within 7 days. Only 1 of these patients was receiving intensive apixaban therapy; the other 2 patients had active cancer and were initiated on treatment at a reduced dose at the physician’s discretion.
  • A univariate Cox proportional hazard regression analysis was performed for 22 bleeding events (comprising major and minor bleeding) and 38 composite clinical events. See Table: Predictors of Clinical Events for Patients With VTE in a Univariate Cox Proportional Hazard Regression Analysis.
  • Adjustments in the multivariable Cox proportional hazard regression analyses were based on Model 1 (DOACs [apixaban and edoxaban], with XARELTO as the reference, age, and active cancer) and Model 2 (DOACs [apixaban and edoxaban], with XARELTO as the reference, age, and anemia). See Table: Multivariate Cox Proportional Hazard Regression Analysis of Bleeding and Composite Clinical Events in the Apixaban or Edoxaban Group Compared With XARELTO.

Roupe et al (2025)⁵ conducted an observational, register-based cohort study of Swedish patients aged ≥65 years with a first-time PE or DVT diagnosed between January 1, 2014, and July 1, 2023, who received treatment with XARELTO or apixaban. The study aimed to evaluate whether the bleeding risk among cancer-free patients with VTE aged ≥65 years differed between XARELTO and apixaban treatment. Secondary aims were to compare XARELTO and apixaban in terms of major bleeding risk according to sex and age, as well as all-cause mortality, hospitalization for recurrent PE, bleeding location, and fatal bleeding.

• The primary outcome was major bleeding. Secondary outcomes included all-cause mortality, recurrent PE during treatment, GI bleeding, intracranial bleeding, and fatal bleeding.
• A total of 19,090 patients were included; of these, 7572 patients (39.7%) received XARELTO and 11,518 patients (60.3%) received apixaban.
• During the primary treatment period (0 to 6 months), 284 patients (1.5%) experienced major bleeding events. See Table: Event Rates and Adjusted HRs With 95% CIs for Major Bleeding During Primary and Secondary Treatment.
  • Subgroup analyses of patients receiving full and reduced doses were performed separately; the rate of major bleeding events was higher among XARELTO users than among apixaban users in both dosage groups.
  • The bleeding rate was generally higher in patients receiving reduced-dose vs full-dose therapy.
• During the secondary treatment period (6 months to 5 years), 216 patients (1.9%) experienced major bleeding events. See Table: Event Rates and Adjusted HRs With 95% CIs for Major Bleeding During Primary and Secondary Treatment.
  • Subgroup analyses of full- and reduced-dose treatment groups showed comparable major bleeding rates between XARELTO and apixaban users.
• Propensity score-matched analyses, including 7528 patients in each treatment group, were also conducted. Findings from the matched cohort analyses were similar to those from the main analysis for both the primary and secondary treatment periods.

• Detailed results for secondary outcomes stratified by age (65 to <80 years and ≥80 years) and sex are reported in the publication. For overall results of the secondary outcomes, see Table: Overall Event Rates and Adjusted HRs for All-Cause Mortality, Recurrent PE, GI Bleeding, Intracranial Bleeding, and Fatal Bleeding During Primary and Secondary Treatment.

Liu et al (2022)^6,7 conducted a systematic review and meta-analysis of real-world studies to compare the clinical outcomes between apixaban, XARELTO, edoxaban, and dabigatran in patients with VTE.

• Clinical outcomes included recurrent VTE, death, and different bleeding events, including major, intracranial, GI, hospitalized, and minor bleeding.¹
• Overall, 63,144 patients with VTE from 6 observational studies that reported effectiveness and safety outcomes were included in the meta-analysis.¹
  • No significant difference was reported in recurrent VTE events between the apixaban (n=3011) and XARELTO (n=11,219) groups (odds ratio [OR], 0.65; 95% CI, 0.33-1.27; P=0.22). Additionally, no difference was found between the 2 groups for events of major, intracranial, GI, and hospitalized bleeding and death (P>0.05).
  • Apixaban users reported a 46% lower risk of minor bleeding than XARELTO users (OR, 0.54; 95% CI, 0.37-0.78; P<0.001).
• Adjusted HR was also reported and pooled in the studies.^6,7
  • Apixaban users experienced a significant reduction in the major bleeding (HR, 0.61; P=0.008), minor bleeding (HR, 0.56; P<0.0001), and any bleeding (HR, 0.7; P=0.006) risks compared with XARELTO users.
  • No statistical difference was reported between the 2 groups in recurrent VTE events (HR, 1.02; 95% CI, 0.71-1.47; P=0.93).
  • Based on a study that reported results on death, no difference in the risk of death was found between the apixaban and XARELTO groups (HR, 1.11; 95% CI, 0.87-1.41; P=0.40).

Dawwas et al (2022)⁸ conducted a retrospective, new-user cohort study using the Optum's deidentified Clinformatics^® Data Mart Database to compare the effectiveness and safety of apixaban and XARELTO in patients with VTE with commercial healthcare coverage (excluding dual Medicare enrollment). A subgroup analysis based on age group (<65 and ≥65 years) was also conducted.

• The primary effectiveness outcome was the incidence of recurrent VTE, a composite of DVT and PE. The primary safety outcome was the incidence of bleeding, a composite of GI and intracranial bleeding.
• Overall, 42,143 patients with VTE were included in the cohort.
  • New apixaban users: 15,453
  • New XARELTO users: 15,453
• A total of 387 events of recurrent VTE were observed among 15,453 apixaban users (8.9 events per 100 person-years [PYs]) compared with 478 events among 15,453 XARELTO users (11.2 events per 100 PYs; adjusted marginal HR, 0.78 [95% CI, 0.69-0.9]).
  • Among apixaban vs XARELTO users, the number of events and incidence rate per 100 PYs of DVT were 369 vs 445 and 8.4 vs 10.5 (adjusted marginal HR, 0.84 [95% CI, 0.73-0.97]), respectively, and those of PE were 18 vs 33 and 0.4 vs 0.7 (adjusted marginal HR, 0.56 [95% CI, 0.31-1.01]), respectively.
• A total of 333 events of bleeding were observed among 15,453 apixaban users (7.6 events per 100 PYs) compared with 459 events among 15,453 XARELTO users (10.7 events per 100 PYs; adjusted marginal HR, 0.70 [95% CI, 0.61-0.8]).
  • Among apixaban vs XARELTO users, the number of events and incidence rate per 100 PYs of GI bleeding were 327 vs 423 and 7.0 vs 9.6 (adjusted marginal HR, 0.66 [95% CI, 0.57-0.76]), respectively, and those of intracranial bleeding were 6 vs 6 and 0.1 vs 0.1 (adjusted marginal HR, 0.79 [95% CI, 0.24-2.57]), respectively.
• In a subgroup analysis, the risk of recurrent VTE and bleeding, respectively, was evaluated in 5867 apixaban and XARELTO users, each, who were <65 years old and 9351 apixaban and XARELTO users, each, who were ≥65 years old.
  • The adjusted HR (95% CI) for recurrent VTE and bleeding, respectively, was 0.78 (0.62-0.98; P_interaction=0.64) and 0.77 (0.56-1.06; P_interaction=0.2) in patients aged <65 years and 0.76 (0.64-0.9) and 0.59 (0.50-0.7) in patients aged ≥65 years.

Dawwas et al (2022)⁹ conducted a retrospective new-user cohort study from Optum's deidentified Clinformatics Data Mart Database to analyze and evaluate the effectiveness and safety of apixaban and XARELTO in newly diagnosed patients with VTE between January 1, 2015, and June 30, 2020.

• The primary effectiveness outcome was recurrent VTE, a composite of DVT and PE. The primary safety outcome was a composite of GI and intracranial bleeding.
• A total of 49,900 eligible patients diagnosed with VTE were included in the cohort.
  • New apixaban users: 18,618
  • New XARELTO users: 18,618
• A total of 475 patients had recurrent VTE among 18,618 apixaban users (8.9 events per 100 PYs) compared with 595 patients among 18,618 XARELTO users (11.4 events per 100 PYs; HR, 0.77; 95% CI, 0.69-0.87).
  • The absolute reduction in the probability of recurrent VTE with apixaban compared with XARELTO was 0.006 (95% CI, 0.005-0.011) within 2 months and 0.011 (95% CI, 0.011-0.013) within 6 months of treatment initiation. Results were consistent for apixaban (vs XARELTO) for DVT (HR, 0.85; 95% CI, 0.74-0.97) and PE (HR, 0.59; 95% CI, 0.39-0.91).
• A total of 386 patients experienced GI and intracranial bleeding events among 18,618 apixaban users (7.2 events per 100 PYs) compared with 577 patients among 18,618 XARELTO users (11 events per 100 PYs; HR, 0.6; CI, 0.53-0.69).
  • The absolute reduction in the probability of GI and intracranial bleeding with apixaban compared with XARELTO was 0.011 (95% CI, 0.01-0.011) within 2 months and 0.015 (95% CI, 0.013-0.015) within 6 months of treatment initiation. Results were consistent for apixaban (vs XARELTO) for GI (HR, 0.6; 95% CI, 0.53-0.69) and intracranial (HR, 0.54; 95% CI, 0.14-1.2) bleeding.

Fukasawa et al (2022)¹⁰ conducted a retrospective, new-user cohort study using a nationwide hospital-based administrative database provided by Medical Data Vision Co., Ltd. to compare the effectiveness of DOACs, including apixaban, XARELTO, and edoxaban, in patients with VTE from April 1, 2008, to July 31, 2020. Patients aged 18-99 years who initiated apixaban, XARELTO, and edoxaban between December 21, 2015, and February 2, 2020 (180 days before the end of the study period) were included in the study.

• The primary effectiveness outcome was the incidence of recurrent VTE, defined as a composite of DVT or PE that occurred subsequent to the index VTE.
• The primary safety outcome was the incidence of a composite of GI bleeding or intracranial hemorrhage.
• Of the 6959 patients who were eligible, 1998, 1592, and 3369 patients initiated apixaban, XARELTO, and edoxaban, respectively. After the treatment groups were balanced using the matching weights, 1390, 1172, and 1605 initiators of apixaban, XARELTO, and edoxaban, respectively, were generated.
• Results from the weighted analysis are presented below.
  • Among apixaban vs XARELTO users, the number of events and the adjusted incidence rate per 10,000 person-days of recurrent VTE were 17 vs 19 and 1.4 (95% CI, 0.9-2.3) vs 1.7 (95% CI, 1.1-2.7), respectively.
  • Among apixaban vs XARELTO users, the number of events and the adjusted incidence rate per 10,000 person-days of GI bleeding or intracranial hemorrhage requiring a procedure were 14 vs 11 and 1.2 (95% CI, 0.7-2) vs 1 (95% CI, 0.6-1.8), respectively.
  • Among apixaban vs XARELTO users, the number of events and the adjusted incidence rate per 10,000 person-days of GI bleeding or intracranial hemorrhage requiring a procedure or hospitalization were 36 vs 30 and 3.1 (95% CI, 2.2-4.3) vs 2.8 (95% CI, 2-4), respectively.
  • The adjusted incidence rate ratio (IRR) per 10,000 person-days for recurrent VTE for XARELTO vs apixaban was 1.2 (95% CI, 0.69-2.1).
  • The adjusted IRR per 10,000 person-days for GI bleeding or intracranial hemorrhage requiring a procedure for XARELTO vs apixaban was 0.83 (95% CI, 0.42-1.64).
  • The adjusted IRR per 10,000 person-days for GI bleeding or intracranial hemorrhage requiring a procedure or hospitalization for XARELTO vs apixaban was 0.91 (95% CI, 0.59-1.38).

Dawwas et al (2019)¹¹ conducted a retrospective cohort analysis of data from the Truven Health MarketScan commercial and Medicare Supplement claims databases to analyze and evaluate the effectiveness and safety of apixaban and XARELTO in prevention of recurrent VTE and major bleeding events in newly diagnosed patients with VTE between Jan 1, 2014 and Dec 31, 2016. Patients were excluded if they had used any anticoagulation therapy during the 12-months prior to study treatment.

• Primary efficacy outcome: incidence of recurrent VTE (DVT or pulmonary thrombosis).
• Primary safety outcome: incidence of major bleeding events.
• Secondary safety outcome: incidence of minor bleeding.
• A total of 15,254 patients were included in the cohort.
  • Apixaban users: 3091
  • XARELTO users: 12,163
• The crude incidence of recurrent VTE was 3 per 100 PYs in the apixaban group and 7 per 100 PYs in the XARELTO group.
  • A total of 25 cases of recurrent VTE were reported among apixaban users and 254 cases among XARELTO users.
• The crude incidence of major bleeding was 3 per 100 PYs in the apixaban group and 6 per 100 PYs in the XARELTO group.
  • A total of 28 cases of major bleeding were reported among apixaban users and 188 cases among XARELTO users.
• The use of apixaban compared with XARELTO was associated with a decreased risk of recurrent VTE (HR, 0.37; 95% CI, 0.24-0.55; P<0.0001) and major bleeding events (HR, 0.54; 95% CI, 0.37-0.82; P=0.0031).
• For the secondary safety outcome, the incidence of minor bleeding was 20 per 100 PYs in the apixaban group and 34 per 100 PYs in the XARELTO group.
  • The use of apixaban was associated with lower risk of minor bleeding events than use of XARELTO (HR, 0.57; 95% CI, 0.48-0.67; P<0.0001).

Jin et al (2021)¹² conducted a cohort study analyzing data from the Optum Clinformatics Data Mart Database to assess the safety and efficacy of apixaban and XARELTO for patients with VTE between 2003 and 2019. Patients with a prior diagnosis of either DVT or PE on or before the anticoagulation start date were included in this study. Patients with a prior diagnosis of atrial fibrillation (AF), intracranial hemorrhage, or an unruptured intracranial aneurysm were excluded.

• Primary endpoints: death and hospital readmissions for intracranial hemorrhage, non-intracranial hemorrhage, or recurrent VTE.
• A total of 225,559 patients treated with either warfarin or a DOAC were included; of these, 34,201 received apixaban and 46,007 received XARELTO.
• Apixaban was not associated with improved survival compared to XARELTO (HR, 1.091; 95% CI, 0.843-1.412). Patients receiving apixaban were significantly less likely to experience a hemorrhagic event while on anticoagulation (HR, 0.581; 95% CI, 0.445-0.758).
• Compared with XARELTO, apixaban was associated with a decreased risk of non-intracranial hemorrhage (subdistribution HR [sHR; emergent hemorrhage], 0.56; 95% CI, 0.423-0.741), but not intracranial hemorrhage, and recurrent VTE (sHR, 0.802; 95% CI, 0.651-0.988) risk when adjusting for mortality as a competing risk. This was primarily in emergent readmissions (sHR, 0.515; 95% CI, 0.372-0.711; sHR [emergent recurrent VTE], 0.636; 95% CI, 0.488-0.83).

Aryal et al (2019)¹³ conducted a systematic review of studies to further compare apixaban with XARELTO in patients with acute VTE from multiple studies done in real-world settings.

• Primary efficacy outcome: recurrence of VTE (composite of any recurrent DVT or PE).
• Primary safety outcomes: clinically relevant major bleeding was reported (composite of bleeding requiring intervention or transfusion, cardiac tamponade, or pericardial effusion requiring drainage, retroperitoneal bleeding, intracranial bleed, massive hemoptysis, hemithorax, bleeding requiring extra hospital stay).
• Secondary safety outcomes: minor bleeding.
• Out of 5 selected studies, a total of 45,468 patients were analyzed for the primary efficacy of recurrent VTE and the safety outcomes of major bleeding and minor bleeding events.
• In 3 studies with 24,401 patients, recurrent VTE of up to 6 months occurred in 56 of 4897 patients (1.14%) in the apixaban group and 258 of 19,144 patients (1.35%) in the XARELTO group (rate ratio [RR], 0.89; 95% CI, 0.67-1.19; P=0.45; I²=0%)
• Clinically relevant major bleeding occurred in 85 of 11,559 patients (0.74%) in the apixaban group and 350 of 33,909 patients (1.03%) in the XARELTO group (RR, 0.73; 95% CI, 0.58-0.93; P=0.01; I²=0%).
• In a sensitivity analysis of 3 studies, clinically relevant nonmajor bleeding occurred in 169 of 3417 patients (4.95%) in the apixaban group and 1094 of 12,475 patients (8.77%) in the XARELTO group (RR, 0.59; 95% CI, 0.5-0.7; P=0.01; I²=0%).
• The composite outcomes of major and minor bleeding occurred in 190 of 3417 patients (5.56%) in the apixaban group and 1186 of 12,475 patients (9.51%) in the XARELTO group (RR, 0.6; 95% CI, 0.52-0.7; P=0.01; I²=0%).
• The composite outcomes of VTE and major bleeding occurred in 102 of 4897 patients (2.08%) in the apixaban group and 483 of 19,144 (2.52%) in the XARELTO group (RR, 0.79; 95% CI, 0.58-1.06; P=0.12; I²=38%).

Bott-Kitslaar et al (2019)¹⁴ conducted a prospective analysis to compare efficacy and safety of XARELTO vs apixaban for the treatment of acute VTE in consecutive patients enrolled in the Mayo Thrombophilia Clinic Registry between March 1, 2013 and January 30, 2018.

• Primary efficacy outcome: symptomatic, recurrent, adjudicated VTE; primary safety outcome: major bleeding.
• Secondary safety outcomes: clinically relevant nonmajor bleeding.
• Of the 1696 enrolled patients, 600 (38%) were treated with apixaban (n=302, 50%) or XARELTO (n=298, 50%) within the first 14 days of VTE diagnosis and completed ≥3 months of anticoagulant therapy or had an outcome event.
• Seven (2.3%) apixaban-treated patients and 6 (2%) XARELTO-treated patients experienced recurrent VTE (adjusted HR, 1.4; 95% CI, 0.5-3.8). There was no confirmed or possible fatal PE.
  • At 3 months of follow-up, the VTE recurrence rate for apixaban vs XARELTO was 1% vs 0.7% (P=0.66); at 6 months, the rate was 2.3% vs 1.3% (P=0.37).
• Major bleeding occurred in 11 (3.6%) apixaban-treated patients and 9 (3%) XARELTO-treated patients (adjusted HR, 1.2; 95% CI, 0.5-3.2).
  • The 3-month major bleeding rate was 2% for both apixaban- and XARELTO-treated patients (P=0.98).
• Clinically relevant nonmajor bleeding occurred in 7 (2.3%) apixaban-treated patients and in 20 (6.7%) XARELTO-treated patients (adjusted HR, 0.4; 95% CI, 0.2-0.9).
  • The 3-month clinically relevant nonmajor bleeding rate for apixaban- vs XARELTO-treated patients was 1% vs 3.7% (P=0.03).
• The rates of composite major bleeding or clinically relevant nonmajor bleeding were similar (adjusted HR, 0.6; 95% CI, 0.3-1.2).

Specific Populations

Akgun et al (2026)¹⁵ conducted a study using data from the TriNetX research network to evaluate recurrent VTE and bleeding outcomes in adults with active solid tumors receiving XARELTO (20 mg) or apixaban (5 mg). Active cancer was defined as receipt of chemotherapy, radiation therapy, or cancer surgery within 6 months of cancer diagnosis. Eligible patients experienced acute DVT or PE within 30 days of the cancer index date. Propensity score matching (1:1) was performed with each cohort comprising 5690 patients.

• The primary outcome was recurrent DVT or PE at 1 year. Secondary outcomes were all-cause mortality, intracranial hemorrhage, GI bleeding, anemia, and blood transfusion. See Table: Clinical Outcomes With XARELTO vs Apixaban in Patients With Active Solid Tumors at 1 Year.
• Rates of intracranial hemorrhage and GI bleeding were similar between the XARELTO and apixaban cohorts.

de Matos et al (2026)¹⁶ conducted a systematic review and meta-analysis to evaluate the efficacy and safety of XARELTO vs apixaban in patients with GI cancers.

• Outcomes of interest included recurrent VTE, major bleeding, and clinically relevant nonmajor bleeding. Subgroup analyses were performed for luminal GI cancers (esophageal, gastric, small bowel, and colorectal cancers) and nonluminal hepatopancreatobiliary malignancies. Apixaban served as the intervention and XARELTO as the control.
• A total of 3 observational studies met the inclusion criteria, comprising 996 patients.
• The pooled analysis showed no significant difference in recurrent VTE for apixaban vs XARELTO (OR, 0.8; 95% CI, 0.42-1.51). OR for major bleeding was 0.54 (95% CI, 0.29-1.03), and the difference was not statistically significant. OR for clinically relevant nonmajor bleeding was 0.4 (95% CI, 0.16-1.01).
• Subgroup analyses were conducted according to the tumor location.
  • Among patients with luminal GI cancers, no significant difference in the risk of major bleeding was observed between the treatment groups (OR, 1.23; 95% CI, 0.43-3.5).
  • Among patients with nonluminal GI cancers, the risk of major bleeding was significantly lower with apixaban than with XARELTO (OR, 0.28; 95% CI, 0.08-0.94).
  • For clinically relevant nonmajor bleeding, OR was 0.53 (95% CI, 0.2-1.38) for patients with luminal GI cancers and 0.47 (95% CI, 0.09-2.35) for patients with nonluminal GI cancers; neither comparison reached statistical significance.

Lindhoff-Last et al (2026)¹⁷ reported findings from the prospective, multicenter, noninterventional HEMBLED registry conducted across 8 German outpatient coagulation centers between 2020 and 2024. The study enrolled consecutive menstruating women aged 18 to 50 years with regular menstrual bleeding and objectively confirmed first or recurrent symptomatic VTE who were receiving maintenance therapeutic-dose DOAC therapy (including XARELTO [20 mg once daily], apixaban [5 mg twice daily], dabigatran [150 mg twice daily], or edoxaban [60 mg once daily]) for at least 7 days before study inclusion and were planned to continue on the same therapeutic anticoagulation regimen for at least 4 months after enrollment. Women using hormonal contraceptives or intrauterine devices were excluded. Women who developed VTE while using oral contraceptives were eligible only if hormonal contraception had been discontinued for at least 25 days before inclusion in the registry.

• The primary objective was to evaluate and compare the incidence of heavy menstrual bleeding (HMB) using a modified Pictorial Blood Assessment Chart (PBAC) score.
• The primary outcome was the incidence of HMB at least once during follow-up. Secondary outcomes included the prevalence of von Willebrand’s disease and the association of HMB with von Willebrand’s disease, age, blood group, uterine pathology, iron deficiency, hemoglobin level, and documented nonsteroidal anti-inflammatory drug (NSAID) use.
• At baseline, 45 patients (62%) received apixaban and 19 patients (26%) received XARELTO.
• The mean PBAC score was 145 points (95% CI, 103-204) in the XARELTO group and 93 points (95% CI, 73-118) in the apixaban group. The PBAC score in the XARELTO group was 54% higher than that in the apixaban group (P=0.0193).
  • In a sensitivity analysis excluding 6 patients for whom the anticoagulant was switched before enrollment because of increased menstrual bleeding, the PBAC score in the XARELTO group remained 47% higher than that in the apixaban group (P=0.0426).
  • HMB occurred in 79% of patients receiving XARELTO and in 53% of patients receiving apixaban; the difference did not reach statistical significance (P=0.0913).
  • NSAID use was not significantly associated with the PBAC score (P=0.9548).
  • No significant association was observed between the PBAC score and age, baseline International Society of Thrombosis and Hemostasis (ISTH) bleeding score, iron deficiency, hemoglobin level, uterine myomas, or adenomyosis (P>0.20 for all comparisons).
  • No significant difference was observed between the treatment groups in baseline hemoglobin level (P>0.2) or in changes in hemoglobin over time (P>0.2).
• The mean duration of menstrual bleeding was 6 days (95% CI, 5.2-6.8) with XARELTO and 5.4 days (95% CI, 4.9-5.9) with apixaban. No significant difference was reported between the treatment groups.
• Self-reported intracyclic bleeding was observed in in 0 of 19 patients (0%) receiving XARELTO and 10 of 45 patients (22%) receiving apixaban.
• No significant difference in the ISTH bleeding score was reported between the treatment groups.
  • Additional bleeding events were reported in 3 patients. One patient treated with XARELTO experienced HMB accompanied by blood deposits in the stool; oral iron supplementation was administered, and spontaneous improvement was observed without changes to anticoagulant therapy.

Lutsey et al (2026)¹⁸ conducted a new-user, active-comparator study using a Medicare 20% sample of beneficiaries aged ≥65 years with fee-for-service coverage under Parts A (hospital insurance), B (medical insurance), and D (prescription drug coverage). The study included patients with cancer-associated VTE and compared the risk of death and hospitalized bleeding according to the oral anticoagulant prescribed.

• The outcomes of interest were death and hospitalized bleeding events. See Tables: Association of Choice of Anticoagulant and Hospitalized Bleeding Within 6 Months of Cancer-Associated VTE: Medicare 20% Sample (2011-2019) and Association of Choice of Anticoagulant and Mortality Within 6 Months of Cancer-Associated VTE: Medicare 20% Sample (2011-2019).

Nazzal et al (2026)¹⁹ conducted a study using data from the TriNetX US Collaborative Network (71 healthcare organizations) to evaluate outcomes in adults with pancreatic cancer and VTE treated with XARELTO or apixaban. Propensity score matching was applied to generate balanced treatment cohorts comprising 3282 patients each.

• Outcomes assessed comprised mortality, GI bleeding, intracranial bleeding, recurrent PE, DVT, and stroke. See Table: Efficacy and Safety Outcomes of XARELTO vs Apixaban.

Salameh et al (2026)²⁰ conducted a study using data from the TriNetX US Collaborative Network to evaluate the efficacy and safety of XARELTO and apixaban in adults with colon cancer and VTE. Propensity score matching was applied to create balanced treatment cohorts comprising 5331 patients each.

• Outcomes assessed comprised mortality, GI bleeding, intracranial bleeding, recurrent PE, DVT, and stroke. See Table: Efficacy and Safety Outcomes of XARELTO vs Apixaban.

Zahid et al (2026)²¹ conducted a study using data from the TriNetX US Collaborative Network to compare the efficacy and safety of XARELTO vs apixaban in adults with gastric cancer and VTE. Propensity score matching generated 2 balanced cohorts comprising 1266 patients each.

• Outcomes assessed comprised mortality, upper/lower GI bleeding, intracranial bleeding, recurrent PE, DVT, and stroke. See Table: Efficacy and Safety Outcomes of XARELTO vs Apixaban.

Sarlon-Bartoli et al (2025)²² conducted the French multicenter, cross-sectional, observational GENB-OAC study across 10 hospitals between December 2018 and December 2022. The study prospectively evaluated and compared the prevalence of abnormal uterine bleeding (AUB) among women of reproductive age receiving oral anticoagulants (XARELTO, apixaban, or a vitamin K antagonist [VKA]) for a first or recurrent confirmed VTE as well as among healthy controls. The study also assessed the quality of life (QoL) in these 4 groups and in the general French female population of the same age.

• Eligible participants were women aged ≥18 years who were of reproductive age and had active menstrual cycles and a first or recurrent confirmed VTE that was treated with XARELTO, apixaban, or a VKA, regardless of the time since the VTE event.
• The primary outcome was the proportion of women with major genital bleeding, based on a combination of different AUB assessment methods. Secondary outcomes were the individual components of the primary outcome. See Table: Abnormal Uterine Bleeding and Genital Bleeding Outcomes by Anticoagulant Group. QoL was assessed using the World Health Organization Quality of Life Brief Version (WHOQOL-BREF) questionnaire.
• A total of 445 women were prospectively enrolled, including 123 receiving XARELTO, 122 receiving apixaban, 81 receiving VKAs, and 119 healthy controls.
• The major genital bleeding rate did not differ significantly according to the timing of the VTE event, irrespective of the anticoagulant administered (P=0.52). No significant differences were observed in WHOQOL-BREF domain scores across the 3 oral anticoagulant treatment groups.

Sun et al (2025)²³ conducted a retrospective, new-user cohort study using 2 US administrative claims databases (Medicare claims and commercial claims) to evaluate the safety and effectiveness of XARELTO vs apixaban in adults with cancer-associated VTE. Data were obtained from the Merative MarketScan Research Database (January 2016 to December 2022), which included patients aged 18 to 64 years, and from a 20% random sample of Medicare fee-for-service beneficiaries (January 2016 to December 2020), which included patients aged ≥65 years. Eligible patients had active cancer and had been newly initiated on apixaban or XARELTO within 30 days following an index VTE event.

• Primary outcomes were recurrent VTE leading to hospitalization, major bleeding leading to hospitalization, and clinically relevant nonmajor bleeding leading to hospitalization or an outpatient visit.
• The study included 10,589 patients with cancer-associated VTE, comprising 6097 patients from MarketScan and 4492 Medicare beneficiaries. Overall, 4260 patients (40.2%) were initiated on XARELTO, and 6329 patients (59.8%) were initiated on apixaban.
• At 6 months, the mean follow-up duration was approximately 129 days for XARELTO users and 126 days for apixaban users. During the extended follow-up period, the mean follow-up duration was 342 days for XARELTO users and 289 days for apixaban users, and nearly half of the patients remained on treatment. See Tables: Adjusted Incidence Rates per 100 Person-Years for Clinical Outcomes With XARELTO vs Apixaban and HRs for Major Bleeding, Clinically Relevant Nonmajor Bleeding, and Recurrent VTE With XARELTO vs Apixaban.
• Findings remained consistent in sensitivity analyses that used a 7-day exclusion window rather than the 30-day window for defining recurrent VTE, included or excluded patients with short-term low-molecular-weight heparin use at baseline, and applied an intention-to-treat approach without censoring patients for treatment switching or discontinuation.

Sperry et al (2024)²⁴ conducted a multicenter, retrospective, observational study across 6 academic medical centers that compiled deidentified data from adults aged ≥18 years who received a DOAC (XARELTO, apixaban, dabigatran, or edoxaban) for the treatment of acute VTE between January 1, 2013, and December 31, 2021. Patients were stratified according to the body mass index at the time of index VTE (<40 kg/m² vs ≥40 kg/m²).

• The primary efficacy outcome was recurrent VTE within 12 months of the index event. The primary safety outcome was major bleeding, defined as fatal bleeding, bleeding at a critical site, bleeding associated with a hemoglobin decrease of ≥2 g/dL, or bleeding requiring transfusion of ≥2 units of packed red blood cells according to ISTH criteria. Exploratory secondary outcomes were time to recurrent VTE and time to major bleeding.
• Among the 485 patients included in the study, XARELTO was prescribed in 111 patients (22.9%) and apixaban in 373 patients (76.9%).
• No difference was observed in recurrent VTE in patients treated with XARELTO vs apixaban (6.3% vs 2.9%; unadjusted OR, 0.45; 95% CI, 0.16-1.41); similarly, no difference was observed in major bleeding (4.5% vs 4%; unadjusted OR, 0.89; 95% CI, 0.3-3.2). See Table: Recurrent VTE and Major Bleeding Outcomes by BMI Category.
• Seven of the 89 patients (7.9%) who received the full lead-in dose of XARELTO experienced recurrent VTE, whereas none of the 22 patients who received an alternative dosing strategy experienced recurrent VTE (P>0.05).
• Nine of the 280 patients (3.2%) who received the full lead-in dose of apixaban experienced recurrent VTE, whereas 2 of the 93 patients (2.2%) who received an alternative dosing strategy experienced recurrent VTE (P>0.05).

Lawal et al (2023)²⁵ conducted a retrospective, real-world cohort study using administrative claims from the Optum Clinformatics Data Mart database collected between January 1, 2010, and December 31, 2017. They evaluated the clinical benefit of DOACs (individually and as a class) vs warfarin and compared DOACs with each another in adult patients (aged ≥18 years) with VTE and chronic liver disease who were initiated on DOACs (XARELTO, apixaban, edoxaban, or dabigatran) or warfarin between January 1, 2011, and December 31, 2017, after the first diagnosis of VTE.

• The primary outcome was the net clinical benefit, defined as a composite of hospitalization for recurrent VTE and hospitalization for major bleeding. Secondary effectiveness and safety outcomes comprised all-cause mortality and clinically relevant nonmajor bleeding. See Table: Incidence Rates and Effect Estimates for Clinical Outcomes With Apixaban vs XARELTO in Patients With VTE and Chronic Liver Disease.
• A total of 8477 eligible patients were identified before propensity score matching, including 5337 warfarin initiators (63%) and 3140 DOAC initiators (37%). After propensity score matching, the matched cohorts consisted of the following:
  • Apixaban-XARELTO pairs: 895
  • XARELTO-warfarin pairs: 2161
  • Apixaban-warfarin pairs: 895
  • DOAC-warfarin pairs: 2361

Tsai et al (2022)²⁶ conducted a cohort study using the Chang Gung Research Database to compare the effectiveness and safety of DOACs (XARELTO, apixaban, dabigatran, or edoxaban) in Asian patients who were newly diagnosed and hospitalized with VTE between January 1, 2012, and December 31, 2019.

• The effectiveness and safety clinical outcomes include recurrent VTE and any major bleeding event (intracranial hemorrhage, major GI bleeding, other critical site bleedings, or a hemoglobin decrease of ≥2 g/dL over 24 hours). The primary outcomes were defined as the composite of effectiveness and safety (see Table: Effectiveness and Safety Clinical Outcomes)

DeCamillo et al (2020)²⁷ conducted a multicenter retrospective case series of young adult patients at 2 large academic medical centers, to assess the safety of DOACs for VTE therapy between 2015-2016. Patients between the ages of 18-40 when DOAC was initiated were included in this study.

• The assessments included frequency and percentage of ischemic stroke, recurrent VTE, bleeding events (ISTH defined as major and clinically relevant nonmajor)
• Fifty-seven patients met the eligibility criteria.
• One (1.8%) patient had a recurrent DVT. The DVT occurred about 12 days after initiating XARELTO, and the patient had reported missing 3 doses. No patient experienced an ischemic stroke.
• Seven of the 57 patients (12.3%) experienced a bleeding event. Six of the 7 patients were being treated with XARELTO. The seventh patient was treated with apixaban and experienced HMB that did not qualify as a major or clinically relevant nonmajor bleeding event.
• One (1.8%) bleeding event was categorized as major (patient had heavy menses and required transfusion). The bleeding occurred after 17 days of XARELTO 15 mg twice daily. XARELTO was discontinued in this patient due to the bleeding event and no other anticoagulation therapy was initiated. The other 6 patients experienced clinically relevant nonmajor bleeding events. Two were GI related while the other 4 experienced heavy menses.

Trujillo-Santos et al (2020)²⁸ conducted a prospective study using the Registry of patients with VTE (RIETE) database to compare the rates of the composite of VTE recurrences or major bleeding in fragile patients with VTE using XARELTO or apixaban for initial or long-term therapy. Between January 2013 and October 2019, 14,831 fragile patients with acute VTE were recruited, of which 999 patients received DOACs.

• Overall, 711 patients started XARELTO, and 288 patients started apixaban <48 hours after VTE diagnosis; of these patients, 882 were ≥75 years old, 370 had creatinine clearance ≤50 mL/min, and 92 weighed ≤50 kg. In the XARELTO and apixaban groups, 25% and 40% of patients received nonrecommended doses, respectively.
• When analyzing patients receiving recommended doses (n=705), there were no differences between treatments in the rates of VTE recurrence (RR, 0.99; 95% CI, 0.2-4.92), major bleeding (RR, 1.16; 95% CI, 0.24-5.57), the composite outcome (RR, 1.08; 95% CI, 0.35-3.3), and all-cause death (RR, 0.99; 95% CI, 0.32-3.08).
• Multivariable analysis revealed that patients receiving XARELTO in the entire cohort had a nonsignificantly higher risk for the composite outcome than those receiving apixaban (HR, 1.72; 95% CI, 0.63-4.69). The adjusted HR when only considering patients that received recommended doses was 1.34 (95% CI, 0.35-5.06).

Wysokinski et al (2020)²⁹ compared VTE recurrence and bleeding in patients with extremes in body weights, <60 kg and >120 kg, to patients with body weight between 60 kg and 120 kg, treated with apixaban or XARELTO. Consecutive patients enrolled in the Mayo Clinic VTE Registry between March 1, 2013, and August 10, 2019, with acute VTE were prospectively followed.

• Among 2577 included patients: there were 2124 (82%) with a body weight between 60 to 120 kg (reference bodyweight; RBW), 223 (8.7%) with a body weight <60 kg (low bodyweight; LBW), and 230 (8.9%) with a body weight >120 kg (high bodyweight; HBW).
• The 3-month incidence of major bleeding among patients treated with apixaban or XARELTO was significantly higher (P=0.03) in patients with LBW (4.4%) compared to the RBW group (1.1%) and remained significant at 6 months (4.4% vs 1.4%; P=0.05).
• The 3-month incidence of VTE recurrence among patients treated with apixaban or XARELTO was similar in the LBW and HBW groups compared to the RBW group.
• Among patients receiving XARELTO who had cancer, the HBW group had higher VTE recurrence compared to the RBW group (P=0.01).

Bleeding Events

Mahesri et al (2026)³⁰ conducted a new-user, active-comparator cohort study as part of the RCT-DUPLICATE initiative to emulate the designs and measurements of the COBRRA-VTE and COBRRA-AF trials. The emulations used 3 deidentified US healthcare claims data sources: 2 commercial health insurance claims databases, namely the Optum Clinformatics Data Mart (2004-2020) and IBM MarketScan (2003-2019), and subsets of Medicare Parts A, B, and D (2009-2017) comprising patients dispensed an oral anticoagulant.

• Eligible patients were those aged ≥18 years who had been initiated on XARELTO or apixaban from the date of apixaban approval for VTE (August 21, 2014, for COBRRA-VTE) or AF (December 28, 2012, for COBRRA-AF) through the end of data availability in each database.
  • For the COBRRA-VTE emulation, patients were required to have an inpatient or emergency department diagnosis of VTE within 14 days before or on the cohort-entry date.
• The primary outcome was a composite of major bleeding and clinically relevant nonmajor bleeding. Within each database, apixaban initiators were matched 1:1 with XARELTO initiators using propensity score matching.
• COBRRA-VTE emulation:
  • A total of 41,337 eligible patients with VTE were identified, including 23,424 XARELTO initiators and 17,913 apixaban initiators. The propensity score-matched cohort comprised 14,023 matched pairs. For results of the primary as-treated analysis, see Tables: Composite Major Bleeding and Clinically Relevant Nonmajor Bleeding Outcomes in the COBRRA-VTE Emulation and Database-Specific HRs for the Composite of Major Bleeding and Clinically Relevant Nonmajor Bleeding in the COBRRA-VTE Emulation.
  • In the intention-to-treat analysis, which included 14,079 matched pairs followed for up to 1 year, HR for major or clinically relevant nonmajor bleeding with apixaban vs XARELTO was 0.71 (95% CI, 0.62-0.81).

Howe et al (2019)³¹ studied overall bleeding rates between apixaban (n=716) and XARELTO (n=452) using a retrospective chart review of Veterans between March 15, 2016 to March 15, 2017 from the Richard L. Roudebush VA Medical Center.

• The rates of bleeding for Veterans taking XARELTO or apixaban did not differ significantly (1.95% vs 1.05%, P>0.05). No differences were seen in Veterans receiving XARELTO or apixaban for long term VTE treatment (2.68% vs 0.32%, P>0.05) when further stratified by indication.
• The analysis did not detect any statistically significant differences between apixaban and XARELTO in terms of overall, (ARR, 0.9% per 100 patient-years; 95% CI, 0.58 to 2.38%; P>0.05) major, (ARR, 0.22% per 100 patient-years; 95% CI, 0.74 to 1.17%; P>0.05) or nonmajor clinically relevant (ARR, 0.35% per 100 patient-years; 95% CI, 0.57 to 1.27%; P>0.05) bleeding.
• Rates of bleeding in Veterans taking XARELTO or apixaban for long term VTE treatment (3.97% vs 8.03%, P<0.0001; 0.14% vs 15.51%, P<0.0001) were significantly lower than those reported by the primary literature. GI bleeds were the most common type of clinically relevant bleed in this patient population for both XARELTO (58%) and apixaban (70%).

Lutsey et al (2019)³² characterized the rate of major hospitalized bleeding events associated with the use of apixaban (n=6786), XARELTO (n=30,982), and warfarin (n=46,217) in a retrospective, cohort study. VTE patient health claims data obtained from the MarketScan data warehouse from January 1, 2011, to December 31, 2016, were utilized.

• Of the 83,985 VTE patients, a total of 1944 hospitalized bleeding events occurred during the first 180 days after oral anticoagulation initiation. The cumulative incidence of hospitalized bleeding was lower among new users of apixaban (1.1%) than among new users of XARELTO (2%) or warfarin (2.7%).
• The rate of hospitalized bleeding was lower among apixaban users than among XARELTO (HR, 0.58; 95% CI, 0.41-0.8) or warfarin (HR, 0.68; 95% CI, 0.5-0.92) users.
• Apixaban was associated with lower hospitalized bleeding risk than XARELTO in several sensitivity analyses.

Healthcare Utilization

Ashton et al (2025)³³ conducted a real-world, retrospective, observational study using data from the Mass General Brigham Research Patient Data Registry (MGB RPDR) PE Data Mart (January 2013 to May 2023) to compare the 30-day risk of all-cause hospital readmission among patients with PE treated with XARELTO vs apixaban.

• Eligible adults were those who were hospitalized with ≥1 diagnosis of PE, who were initiated on XARELTO (15 mg or 20 mg) or apixaban, who received the index agent as the first oral anticoagulant prescribed after discharge from the index PE hospitalization, and who had ≥6 months of clinical activity before admission to the index PE hospitalization.
• The study included 686 patients in the XARELTO group and 2207 patients in the apixaban group. The outcome of interest was the risk of all-cause hospital readmission, assessed for up to 90 days following discharge from the index PE hospitalization.
• Patients in the XARELTO group had a significantly lower risk of 30-day all-cause hospital readmission following discharge from the index PE hospitalization compared with patients in the apixaban group. See Table: Risk of All-Cause Hospital Readmission With XARELTO vs Apixaban in Patients With PE.
• Specifically, the risk of all-cause hospital readmission was 26% lower at 30 days, 26% lower at 60 days, and 19% lower at 90 days with XARELTO compared with apixaban following discharge from the index PE hospitalization.

Schaefer et al (2025)³⁴ conducted a registry-based cohort study using Michigan Anticoagulation Quality Improvement Initiative (MAQI²) registry data collected from January 2009 to June 2023 to compare patient characteristics and outcomes among commonly used oral anticoagulants. Eligible patients were aged ≥18 years, were initiated on or switched to an oral anticoagulant for AF and/or VTE, and had at least 3 months of follow-up available.

• Among 13,435 eligible patients, 1395 received XARELTO and 3536 received apixaban. Following propensity score matching, 1395 patients receiving XARELTO were compared with 1395 patients receiving apixaban. For outcomes from propensity score-matched groups, see Table: Adjusted Clinical Event Rates per 100 Patient-Years in Propensity-Matched XARELTO and Apixaban Groups.

• In a sensitivity analysis excluding patients receiving reduced-dose DOAC therapy, the baseline study cohort comprised 12,648 patients. In the propensity score-matched cohorts (1256 patients per group), findings were similar to those of the primary analysis, although the mortality rate for XARELTO vs apixaban was 3.1 vs 2.8 deaths/100 patient-years (P=0.54).
• In a second sensitivity analysis restricted to patients with VTE only, patients with AF alone or AF plus VTE were excluded, resulting in 5646 eligible patients. In the propensity score-matched cohorts (713 patients per group), bleeding patterns were similar to those observed in the primary analysis; however, the rate of major bleeding for XARELTO vs apixaban was 4.4 vs 2.9 major bleeds/100 patient-years (P=0.06). Differences in emergency room visits and mortality were no longer statistically significant.

Lutsey et al (2020)³⁶ evaluated whether in the first 6 months post-VTE diagnosis, healthcare utilization differed whether the patient was prescribed apixaban (n=7673), XARELTO (n=10,414), or warfarin (n=5777) for primary treatment of their VTE event. IBM MarketScan Commercial Claims and Encounters and Medicare Supplemental and Coordination of Benefits databases between 2016 and 2017 were utilized.

• The mean hospitalization rates were 24% lower (IRR, 0.76; 95% CI, 0.69-0.83) for patients prescribed XARELTO and 22% lower (IRR, 0.78; 95% CI, 0.71-0.87) for patients prescribed apixaban, as compared with those prescribed warfarin (IRR, 1 [reference]).
• Healthcare utilization was similar between apixaban and XARELTO users. When comparing apixaban to XARELTO, there were no differences in the number of hospitalizations, days hospitalized, or emergency department visits.
• In a secondary analysis, the IRRs for hospitalized bleeding associated with XARELTO and apixaban were 0.79 (95% CI, 0.54-1.15) and 0.57 (95% CI, 0.38-0.87) as compared to warfarin, respectively. The IRR for hospitalized bleeding days was lower for both apixaban (0.73; 95% CI, 0.36-1.49) and XARELTO (0.58; 95% CI, 0.30-1.14), compared to warfarin.

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, DERWENT^® (and/or other resources, including internal/external databases) was conducted on 21 September 2026.