Real-world Evidence of XARELTO - Prophylaxis of Deep Vein Thrombosis in Patients Undergoing Knee or Hip Replacement Surgery

Summary

• The XAMOS study demonstrated that XARELTO was associated with lower incidences of symptomatic thromboembolic events compared with standard of care (SoC), without significant increases in major bleeding events.^1-4
• A retrospective analysis using data from the TriNetX Research Network showed that, following primary total hip arthroplasty (THA), low-dose aspirin (LDA; 81 mg) was associated with 90-day venous thromboembolism (VTE) outcomes comparable to those with XARELTO across both high- and low-risk patient cohorts, with no statistically significant differences in deep vein thrombosis (DVT; high-risk patients: odds ratio [OR], 1.19; 95% confidence interval [CI], 0.66-2.16; P=0.56) or pulmonary embolism (PE; OR, 0.94; 95% CI, 0.48-1.82; P=0.84). Similarly, in the low-risk patients, XARELTO-only and LDA-only regimens also did not exhibit statistically significant differences in the incidence of DVT or PE events.⁵
• A retrospective study of 1164 patients undergoing primary total knee arthroplasty (TKA; n=244) or THA (n=920) reported 3 thrombosis and 121 hematomas among patients receiving XARELTO (n=974) and 2 thrombosis and 25 hematomas among patients receiving aspirin (n=190). A multivariate machine-learning (ML) analysis showed an OR for bleeding risk of 0.96 (95% CI, 0.70-1.31; P=1.00) for XARELTO and 1.04 (95% CI, 0.76-1.43; P=1.00) for aspirin.⁶
• A hospital-based prospective comparative study conducted at BGSGIMS, Bengaluru, India between December 2022 and December 2024 included 30 patients undergoing total knee replacement (TKR). Of these, 12 patients received XARELTO (administered for 3 days preoperatively and 10 days postoperatively) and 18 patients received ecosprin (administered for 1 week preoperatively and 4 weeks postoperatively).Major bleeding was reported in 2 patients (1 in each treatment group), and minor bleeding was reported in 10 of 30 patients, with a higher incidence observed in patients receiving XARELTO compared with ecosprin. No cases of venous thromboembolism or pulmonary embolism were observed.⁷
• A retrospective cohort study using Eastern Health Surgery Program electronic health record data included 180 patients undergoing elective THA, of whom 27 (15%) received XARELTO (10 mg once daily) and 153 (85%) received acetylsalicylic acid (ASA; most commonly 325 mg once daily; longer duration). Postoperative VTE was not reported in the XARELTO group, whereas 3 patients (2.0%) in the ASA group experienced VTE; no major bleeding events were reported in either group during the 90-day follow-up.⁸
• A randomized prospective observational study conducted at the MIMS General Hospital, Nellimarla, India, between June 2023 and December 2024 included 50 patients undergoing TKA (n=32) or THA (n=18) who received XARELTO or aspirin for venous thromboembolism prophylaxis. DVT was reported in 3 patients (1 in the XARELTO group and 2 in the aspirin group); no PE events were observed. Major bleeding was reported in 3 patients (all in the XARELTO group), and clinically significant minor bleeding was reported in 5 patients (3 in the XARELTO group and 2 in the aspirin group).⁹
• A retrospective cohort study performed using the Premier Healthcare Database identified 161,585 patients undergoing elective THA or TKA, including 41,899 receiving XARELTO alone and 119,686 receiving XARELTO+tranexamic acid (TXA).¹⁰
  • Univariate regression analyses showed that, compared with XARELTO alone, XARELTO+TXA was associated with lower rates of aggregate bleeding complications (20.6% vs 26.6%; OR, 0.715; P<0.001), transfusion (1.5% vs 4.1%; OR, 0.357; P<0.001), acute anemia (19.8% vs 25.3%; OR, 0.727; P<0.001), and hemorrhage (0.3% vs 0.4%; OR, 0.757; P<0.001), with no difference in hematoma (0.4% vs 0.4%; P=0.295). Multivariable regression analyses confirmed lower rates for aggregate bleeding complications (adjusted odds ratio [aOR], 0.72), transfusion (aOR, 0.39), acute anemia (aOR, 0.73), and hemorrhage (aOR, 0.81), with no significant difference in hematoma (aOR, 0.99).¹⁰
  • Similarly, thromboembolic outcomes were lower with XARELTO + TXA in univariate regression analyses, including DVT (0.9% vs 1.3%; OR, 0.71; P<0.001), PE (0.6% vs 0.8%; OR, 0.73; P<0.001), stroke (0.1% vs 0.2%; OR, 0.70; P=0.009), and myocardial infarction (0.2% vs 0.3%; OR, 0.71; P=0.003), while multivariable regression analyses confirmed lower rates for DVT (aOR, 0.79; P<0.001) and PE (aOR, 0.80; P=0.012).¹⁰
• A retrospective cohort study performed using the Premier Healthcare Database included 5607 adults undergoing aseptic, both-component revision total hip arthroplasty (rTHA; 2016-2023); of these, 2617 patients received XARELTO and 2990 patients received apixaban.¹¹
  • In the XARELTO cohort, initiation on postoperative day 0 (POD 0) versus POD 1 showed similar rates of bleeding outcomes, including aggregate bleeding complications (38.29% vs 39.82%), transfusion (10.03% vs 11.51%), acute anemia (34.28% vs 31.97%), hematoma (2.01% vs 1.26%), and hemorrhage (1.17% vs 1.09%), with no significant differences observed in univariate and multivariable analyses (aggregate: OR,1.066; aOR,0.996; transfusion: OR,1.355; aOR,1.250; acute anemia: OR,1.100; aOR,1.016; hematoma: OR,0.712; aOR,1.070; hemorrhage: OR,1.059; aOR ,0.855).¹¹
  • Similarly, thromboembolic outcomes were comparable between groups, with rates of DVT (1.34% vs 1.09%), PE (0.84% vs 0.59%), stroke (0.33% vs 0.20%), and myocardial infarction (0.17% vs 0.45%), and no significant differences in univariate or multivariable analyses (DVT: OR, 0.812; aOR ,0.879; PE: OR, 0.709; aOR, 0.836; stroke: OR, 0.592; aOR, 1.356; myocardial infarction: OR, 2.673; aOR, 1.293).¹¹
  • In the apixaban cohort, higher rates of aggregate bleeding complications (OR, 0.793; aOR, 0.865), transfusion (OR, 0.572; aOR, 0.702), and acute anemia (OR, 0.795; aOR, 0.890) were observed with POD 0 versus POD 1, with no differences for hematoma or hemorrhage. Rates for thromboembolic outcomes were comparable for DVT, PE, and stroke, whereas myocardial infarction was lower with POD 1 initiation and remained consistently reduced after multivariable analysis (aOR, 0.338).¹¹
• A single-center retrospective study of 2511 patients undergoing primary unilateral THA/TKA (2018-2023) compared the following half-dose vs full-dose DVT prophylaxis regimens: enoxaparin sodium 2000 IU followed by XARELTO 5 mg (n=1246) vs enoxaparin sodium 4000 IU followed by XARELTO 10 mg (n=640). DVT occurred in 11 (0.8%) patients in the half-dose group and 8 (1.3%) patients in the full-dose group (P=0.648), with a TKA subgroup rate of 0.7% vs 1.2% (P=0.679) and a THA subgroup rate of 1.0% vs 1.4% (P=0.773). No PE or mortality events were reported in either group.¹²
• A retrospective study conducted using data from a national healthcare claims database showed that 2.5% and 1.4% of patients in the XARELTO group experienced postoperative VTE and transfusion, respectively, within 90 days of THA. XARELTO was associated with a higher odds of VTE vs aspirin (P<0.0001).¹³
• A retrospective study conducted using data from a national healthcare claims database compared the incidence of postoperative VTE and bleeding by underlying risk factors in patients who underwent primary THA or TKA. It showed that the cumulative 90-day postoperative incidence of VTE and bleeding was 1.86% and 5.33%, respectively. A multivariate analysis showed that the 30-day incidence of VTE and bleeding was lower with aspirin vs XARELTO (P≤0.001).¹⁴
• A real-world study conducted using data from the EPOC (Evidence Based Processes and Outcomes of Care) study compared the effectiveness and safety of aspirin vs low-molecular-weight heparin (LMWH) and direct oral anticoagulants (DOACs) (XARELTO) in patients who underwent elective THA or TKA for osteoarthritis. It showed that 2.4% of patients receiving DOACs and 1.6% of patients receiving aspirin reported symptomatic VTE within 90 days of the operation. The use of prophylactic DOACs was not associated with a significant difference in the 90-day postoperative symptomatic VTE rate as compared to prophylactic aspirin.¹⁵
• A retrospective cohort study in patients who underwent primary elective THA or TKA reported the 90-day risk of postoperative prothrombotic complications and bleeding events with XARELTO vs aspirin and XARELTO vs enoxaparin.¹⁶
  • Patients who received XARELTO after TKA had a higher risk of DVT (P=0.022) and combined bleeding (P<0.001) outcomes than those who received aspirin. Similarly, XARELTO was associated with an increased risk of DVT (P=0.457) and combined bleeding (P<0.001) outcomes than enoxaparin.¹⁶
  • Patients who received XARELTO after THA had a higher risk of DVT (P=0.602) and combined bleeding (P<0.001) outcomes than those who received aspirin. XARELTO and enoxaparin showed a similar DVT risk (P=0.251); however, XARELTO was associated with a higher risk of combined bleeding (P<0.001) events than enoxaparin.¹⁶
• A prospective cohort study conducted in patients who underwent THA and TKA reported a significantly lower incidence of symptomatic DVT in the XARELTO group compared with the dabigatran group (0.3% vs 2.2%; P<0.01). Major bleeding was reported in 1.4%, 1.2%, and 0.8% of patients in the XARELTO, dabigatran, and apixaban groups, respectively.¹⁷
• A retrospective study showed that the overall VTE rates in patients who underwent hip and knee replacement surgery were 1.04% and 0.66% in the inpatient enoxaparin and extended aspirin groups and the modified XARELTO group, respectively.¹⁸
• A nationwide claims database analysis including patients who underwent hip arthroplasty showed that DVT occurred more frequently in the aspirin group compared with the XARELTO group (1.3% vs 0.5%; P<0.013), and major bleeding events were similar between the XARELTO and aspirin groups (2.1% vs 1.9%, respectively; P=0.579).¹⁹
• A retrospective, postmarketing safety surveillance study evaluating major bleeding in patients who underwent total hip replacement (THR) or TKR and received XARELTO showed that the incidence proportion of clinically relevant bleeds based on exploratory analyses of inpatient secondary diagnosis codes or emergency department visits was 0.46% and 0.21%, respectively.²⁰
• Postmarketing safety data evaluating XARELTO use in patients undergoing THR and/or TKR procedures showed major bleeding rates to be 0.04%.²¹
• Additional citations for review have been included in the REFERENCES section.^22,23

Real-World EVIDENCE

The XAMOS (XArelto^® in the prophylaxis of post-surgical venous thromboembolism after elective Major Orthopedic Surgery of hip or knee)^1-4 study was an international, noninterventional, observational, open-label study that assessed the efficacy and safety of XARELTO in daily clinical practice for prophylaxis of VTE in patients after elective THR or TKR.

Inclusion/exclusion criteria: consecutive adult patients (≥18 years of age) undergoing elective THR/TKR (or hip fracture surgery where indicated) were included in the study. Patients were prescribed pharmacological VTE prophylaxis by their treating physician and provided written consent where necessary. Patients were excluded based on the approved local product information.

Study design: the study enrolled 17,701 patients to receive XARELTO or SoC for thromboprophylaxis. Current SoC included LMWHs, fondaparinux, and vitamin K antagonists. The type and dose of the drug, as well as the duration of treatment, was to be determined by the attending physician. Enrolled patients were from 37 countries and 252 centers. Data was collected at the start of therapy, at hospital discharge, 1 week after therapy completion, and 3 months after surgery. Bleeding and other adverse events (AEs) were considered treatment-emergent if the event started on or after the day of the first dose and up to 2 days after the last dose of a VTE prophylactic drug. Serious AEs were followed until a final outcome was obtained.

Outcome measures: the main outcome measures were symptomatic thromboembolic events, bleeding events, uncommon AEs, and mortality. Additional outcome measures included convenience of treatment, health care resource use, compliance, use in special populations such as those with renal impairment, and the use of certain concomitant medications.

Results: a total of 17,413 patients were included in the safety population (XARELTO, n=8778; SoC, n=8635). Demographics of the patient population are presented in Table: Demographic Data. In the SoC group, most patients (81.7%) received LMWHs.

The most commonly reported comorbidity was hypertension (XARELTO, 49.5%; SoC, 53.0%), followed by hypercholesterolemia (XARELTO, 10.6%; SoC, 10.8%), and diabetes mellitus (XARELTO, 10.5%; SoC, 11.7%).²

Compared with SoC, patients receiving XARELTO had a lower incidence of symptomatic thromboembolic events (arterial and venous). The incidences of treatment-emergent bleeding events in the safety populations were similar, as represented in Table: Incidence of Thromboembolic and Other Treatment-Emergent Events.

Hepatic disorders occurred in 46 and 37 patients in the XARELTO (0.52%) and SoC (0.43%) treatment groups, respectively (OR, 1.22; 95% CI, 0.79-1.89). Thrombocytopenia occurred in 7 and 20 patients in the XARELTO and SoC treatment groups, respectively (OR, 0.34; 95% CI, 0.15-0.81). Mortality was low in both groups (0.1% vs 0.1%, respectively) and was not related to treatment.

Wound complications: there was no significant difference in the incidence of treatment-emergent postoperative wound infection or wound hemorrhage between the groups. The incidence of treatment-emergent, postprocedural wound discharge was higher in the XARELTO group than in the SoC group (0.4% vs 0.1%, respectively; OR, 3.65; 95% CI, 1.78-8.24).

The Rating of Health Care Utilization based on patient reporting is presented in Table: Rating of Health Care Utilization.

Concomitant platelet aggregation inhibitor (PAI) users had higher incidences of total symptomatic thromboembolic events than the nonusers in both the treatment groups. The incidence of VTE events was higher in the PAI users vs the nonusers within the SoC group compared with the XARELTO group.

The incidence of total symptomatic thromboembolic events was similar between nonsteroidal anti-inflammatory drug (NSAID) users and nonusers in the XARELTO and SoC groups. XARELTO was associated with a lower incidence of total symptomatic thromboembolic and symptomatic VTE events (0.89% and 0.23%, respectively). See Table: Incidence of Thromboembolic and Treatment-Emergent Bleeding Events in Patients With or Without Concomitant Use of PAIs and NSAIDs.

Tummala et al (2026)⁵ conducted a retrospective analysis using data from the TriNetX Research Network to assess the safety and efficacy of LDA for VTE prophylaxis following primary THA, stratified by patient VTE risk profiles. The study examined contemporary patterns of chemoprophylaxis utilization and compared 90-day VTE incidence and major postoperative outcomes, including bleeding complications, infections, healthcare utilization, and mortality, among patients receiving LDA and those receiving alternative anticoagulant therapies.

• Evaluated prophylactic regimens included LDA (81 mg), high-dose aspirin (325 mg), warfarin, LMWH, factor Xa inhibitors, and direct thrombin inhibitors. Additional subgroup analyses compared outcomes among patients who received LDA monotherapy and those who received either XARELTO alone, or with combination prophylactic regimens consisting of LDA plus other anticoagulants
• Among high-risk patients, comparisons between XARELTO-only and LDA-only regimens prophylaxis demonstrated no statistically significant differences in the incidence of DVT (OR, 1.19; 95% CI, 0.66-2.16; P=0.56) or PE (OR, 0.94; 95% CI, 0.48-1.82; P=0.84), indicating comparable efficacy between the 2 monotherapy approaches. Similarly, in the low-risk cohort, XARELTO-only and LDA-only regimens also did not exhibit statistically significant differences in the incidence of DVT or PE events. See Table: 90-Day Outcomes: Low-Dose Aspirin Only vs XARELTO.

Emelianov et al (2026)⁶ conducted a retrospective study using multivariate ML models to assess the effects of XARELTO and aspirin, administered alone or in combination with ketorolac or celecoxib, on the risk of hematoma and thrombosis.

• The analysis included 1,164 patients who underwent primary TKA (n=244) or THA (n=920). Among patients treated with XARELTO (n=974), 3 thrombosis and 121 hematomas were reported; among patients treated with aspirin (n=190), 2 thrombosis and 25 hematomas were reported.
• A multivariate machine-learning analysis showed minimal difference in bleeding risk between XARELTO (OR, 0.96; 95% CI, 0.70-1.31; P=1.00) and aspirin (OR, 1.04; 95% CI, 0.76-1.43; P=1.00).

Bhargav et al (2025)⁷ conducted a hospital-based prospective comparative study to evaluate the efficacy of XARELTO and ecosprin for the prevention of DVT in post-TKR patients at BGSGIMS, Bengaluru, India over a 2-year period (December 2022 to December 2024).

• Patients received either XARELTO or ecosprin pre- and postoperatively and were assessed for the signs of DVT and PE postoperatively.
• A total of 30 patients were included in the analysis. Of these, 12 patients received XARELTO (administered for 3 days preoperatively and 10 days postoperatively) and 18 patients received ecosprin (administered for 1 week preoperatively and 4 weeks postoperatively).
• Overall, 2 patients experienced major bleeding events, with 1 case reported in each treatment group. Minor bleeding was reported in 10 of 30 patients, with a higher incidence observed in patients receiving XARELTO compared with ecosprin. No cases of VTE or PE were reported.

Norman et al (2025)⁸ conducted a retrospective cohort study to compare postoperative outcomes and prescribing patterns of XARELTO and ASA in adults undergoing elective THA, using data from Eastern Health Surgery Program electronic health records.

• The analysis included 180 patients; of these, 27 (15%) received XARELTO and 153 (85%) received ASA. ASA was most commonly prescribed at a dose of 325 mg once daily, whereas XARELTO was administered at 10 mg once daily; treatment duration was longer in the ASA group.
• Postoperative VTE was not reported in the XARELTO group, whereas 3 (2.0%) patients in the ASA group experienced VTE. No major bleeding events occurred in either treatment group during the 90-day postoperative follow-up period.

Palavalasa et al (2025)⁹ conducted a randomized prospective observational study to compare the effectiveness of XARELTO and aspirin in preventing VTE following TKA or THA. The study included male and female patients who underwent TKA or THA at the MIMS General Hospital, Nellimarla, India over an 18-month period (June 2023 to December 2024).

• A total of 50 patients were enrolled; of these, 32 underwent TKA and 18 underwent THA. Patients received either XARELTO or aspirin for venous thromboembolism prophylaxis. DVT was reported in 3 patients (1 patient in the XARELTO group and 2 patients in the aspirin group). No cases of PE were reported in either treatment group.
• Major bleeding events occurred in 3 patients in the XARELTO group; no major bleeding events were reported in the aspirin group. Clinically significant minor bleeding was reported in 5 patients (3 cases in the XARELTO group and 2 cases in the aspirin group).

Palmer et al (2025)¹⁰ conducted a retrospective cohort study using the Premier Healthcare Database to compare VTE and bleeding outcomes in patients receiving XARELTO alone vs XARELTO+TXA following elective THA or TKA.

• A total of 161,585 patients were identified, including 41,899 (25.9%) patients who received XARELTO alone and 119,686 (74.1%) patients who received XARELTO+TXA. Univariate regression analyses reported aggregate bleeding complications in 26.6% versus 20.6% of patients receiving XARELTO alone and XARELTO+TXA, respectively (OR, 0.715; P<0.001), transfusion in 4.1% versus 1.5% (OR, 0.357; P<0.001), acute anemia in 25.3% versus 19.8% (OR, 0.727; P<0.001), hemorrhage in 0.4% versus 0.3% (OR, 0.757; P<0.001), and hematoma in 0.4% versus 0.4% (P=0.295) within 90 days postoperatively. Multivariable regression analyses adjusting for confounders reported lower rates with XARELTO+TXA for aggregate bleeding complications (aOR, 0.72; 95% CI, 0.70-0.74; P<0.001), transfusion (aOR, 0.39; 95% CI, 0.36-0.42; P<0.001), acute anemia (aOR, 0.73; 95% CI, 0.71-0.75; P<0.001), and hemorrhage (aOR, 0.81; 95% CI, 0.67-0.99; P<0.001). No significant difference was observed for hematoma (aOR, 0.99; 95% CI, 0.82-1.18; P=0.815). See Table: Differences in Bleeding Complications Between the XARELTO and XARELTO+TXA Cohorts.
• Univariate regression analyses reported DVT in 1.3% versus 0.9% of patients receiving XARELTO alone and XARELTO+TXA, respectively (OR, 0.71; P<0.001), PE in 0.8% versus 0.6% (OR, 0.73; P<0.001), stroke in 0.2% versus 0.1% (OR, 0.70; P=0.009), and myocardial infarction in 0.3% versus 0.2% (OR, 0.71; P=0.003).Multivariable regression analyses reported lower rates with XARELTO + TXA for DVT (aOR, 0.79; 95% CI, 0.71-0.87; P<0.001) and PE (aOR, 0.80; 95% CI, 0.70-0.91; P=0.012).See Table: Differences in Thromboembolic Complications Between the XARELTO and XARELTO+TXA Cohorts.

Telang et al (2025)¹¹ compared postoperative bleeding and thromboembolic complications rates among patients receiving XARELTO or apixaban for VTE prophylaxis following rTHA on POD 0 compared to POD 1. Using the Premier Healthcare Database, adults (≥18 years) who underwent aseptic, both-component rTHA between January 1, 2016, and December 31, 2023, were identified.

• A total of 5,607 patients were included; of these, 2,617 (46.67%) received XARELTO and 2,990 (53.33%) received apixaban. In the XARELTO cohort, rates for POD 0 versus POD 1 were 38.29% versus 39.82% for aggregate bleeding complications, 10.03% versus 11.51% for transfusion, 34.28% versus 31.97% for acute anemia, 2.01% versus 1.26% for hematoma, and 1.17% versus 1.09% for hemorrhage. Univariate and multivariable analyses showed no significant differences between patients who received anticoagulation on POD 0 versus POD 1 for aggregate bleeding complications (OR: 1.066; aOR: 0.996), transfusion (OR: 1.355; aOR: 1.250), acute anemia (OR: 1.100; aOR: 1.016), hematoma (OR: 0.712; aOR: 1.070), or hemorrhage (OR: 1.059; aOR: 0.855). In the apixaban cohort, univariate and multivariable analyses showed higher rates with POD 0 versus POD 1 for aggregate bleeding complications (OR: 0.793; aOR: 0.865), transfusion (OR: 0.572; aOR: 0.702), and acute anemia (OR: 0.795; aOR: 0.890), with no differences for hematoma or hemorrhage. See Tables: Rates and Univariate Analysis of Bleeding Outcomes and Multivariable Analysis of Bleeding Outcomes.
• In the XARELTO cohort, rates for POD 0 versus POD 1 were 1.34% versus 1.09% for DVT, 0.84% versus 0.59% for PE, 0.33% versus 0.20% for stroke, and 0.17% versus 0.45% for myocardial infarction. Univariate and multivariable analyses showed no significant differences for DVT (OR: 0.812; aOR: 0.879), PE (OR: 0.709; aOR: 0.836), stroke (OR: 0.592; aOR: 1.356), or myocardial infarction (OR: 2.673; aOR: 1.293). In the apixaban cohort, POD 0 versus POD 1 groups had comparable rates of DVT, PE, and stroke on both univariate and multivariable analyses. However, patients who received apixaban on POD 1 had a lower rate of myocardial infarction compared with POD 0, and this difference persisted after multivariable analysis (aOR: 0.338). See Tables: Rates and Univariate Analysis of Venous Thromboembolic Outcomes and Multivariable Analysis of Venous Thromboembolic Outcomes.

Wang et al (2025)¹² conducted a single-center retrospective study to compare the effectiveness and safety of full-dose vs half-dose anticoagulant regimens for DVT prophylaxis following total joint arthroplasty. A total of 1886 patients who underwent primary unilateral THA or TKA for hip or knee joint disease unresponsive to conservative treatment between 2018 and 2023 were included.

• Patients in the full-dose group received enoxaparin sodium SC injection 0.4 mL (4000 IU) once every 24 hours, starting at 8 hours after surgery, for 48 hours; this was followed by XARELTO PO 10 mg once daily from POD 3 for 14 days. The half-dose group received enoxaparin sodium 0.2 mL (2000 IU) and XARELTO 5 mg using the same schedule.
• DVT occurred in 11 patients (0.8%) in the half-dose group and in 8 patients (1.3%) in the full-dose group; this difference was not significant (P=0.648). In subgroup analyses, the DVT incidence in the half-dose versus full-dose group was 0.7% (4/543) versus 1.2% (4/344) in the TKA subgroup and 1.0% (7/703) vs 1.4% (4/296) in the THA subgroup, with no significant differences in DVT between half-dose and full-dose regimens observed (P=0.679 for TKA; P=0.773 for THA). No cases of PE or mortality were reported in either treatment group.

Moore et al (2024)¹³ conducted a retrospective study using data from a national healthcare claims database to evaluate the incidence of 90-day postoperative VTE and transfusions with prophylactic XARELTO, aspirin, dabigatran, enoxaparin, and warfarin in patients who underwent primary THA (January 01, 2016 to December 31, 2022).

• Of all patients who underwent primary THA, 11,790 received XARELTO, 36,346 received aspirin, 11,380 received enoxaparin, 13,065 received dabigatran, and 6326 received warfarin.
• Among patients receiving XARELTO, 290 (2.5%) and 170 (1.4%) reported postoperative VTE and transfusion within 90 days of THA, respectively. See Table: Incidence of 90-Day Postoperative VTE and Transfusions.
• XARELTO was associated with a higher odds of VTE vs aspirin (P<0.0001). See Table: Odds of 90-Day Postoperative VTE and Transfusions.

Simon et al (2023)¹⁴  conducted a retrospective analysis of data from a national healthcare claims database to compare the incidence of postoperative VTE and bleeding by underlying risk factors in patients who underwent primary THA or TKA (January 01, 2017 to December 31, 2019). Using propensity score matching, these outcomes were also compared for DOACs vs aspirin.

• Of the 29,264 patients who underwent primary THA or TKA, 7068 (24.2%) received XARELTO, 10,082 (34.5%) received aspirin, 5764 (19.7%) received enoxaparin, 3253 (11.1%) received apixaban, and 3097 (10.6%) received warfarin.
• At 30 and 90 days, the cumulative incidence of VTE was 1.19% (95% CI, 1.06-1.32) and 1.86% (95% CI, 1.70-2.02), respectively.
• At 30 and 90 days, the cumulative incidence of bleeding was 3.43% (95% CI, 3.22-3.64) and 5.33% (95% CI, 5.07-5.59), respectively.
• A multivariate analysis showed that at 30 days, the incidence of VTE (OR, 2.00; 95% CI, 1.47-2.74; P<0.001) and bleeding (OR, 1.38; 95% CI, 1.15-1.66; P=0.001) was lower with aspirin vs XARELTO.
• The propensity score-matched cumulative incidences of VTE and bleeding after 30 and 90 days of DOACs vs aspirin are shown in Table: PSM Analysis of Postoperative VTE and Bleeding.

Sidhu et al (2023)¹⁵ conducted a real-world analysis using data from the EPOC study (a multicenter, prospective, observational, cohort study) to evaluate the effectiveness and safety of aspirin vs LMWH and DOACs (XARELTO) after elective THA or TKA for osteoarthritis.

• Of 1867 eligible patients, 170 (9%) received DOACs, 365 (20%) received aspirin, 762 (41%) received LMWH, and 482 (26%) received LMWH and aspirin.
• At 90 days, the rate of symptomatic VTE was 2.4% with DOACs, 1.6% with aspirin (P=0.6), and 2.7% for the entire cohort. See Table: Primary and Secondary Outcomes Within 90 Days.
• Univariate and multivariate analyses showed that the use of prophylactic DOACs was not associated with a significant difference in the 90-day postoperative symptomatic VTE rate as compared to prophylactic aspirin. See Table: Univariate and Multivariate Analysis for Rate of Symptomatic VTE Within 90 Days.

Piple et al (2023)¹⁶ conducted a retrospective cohort study that compared the efficacy and safety of XARELTO with those of aspirin or enoxaparin for VTE prophylaxis in patients who underwent primary elective THA or TKA (January 01, 2015, to December 31, 2020).

• Of the 802,524 patients who underwent primary elective TKA, 86,721 (10.8%) received XARELTO, 408,038 (50.8%) received aspirin, and 108,377 (13.5%) received enoxaparin.
  • After controlling for potential confounding factors, patients who received XARELTO after TKA had a higher risk of combined prothrombotic (P=0.061) and bleeding (P<0.001) outcomes than those who received aspirin. Similarly, XARELTO was associated with an increased risk of combined prothrombotic (P=0.499) and bleeding (P<0.001) outcomes than enoxaparin.
• Of the 445,570 patients who underwent primary elective THA, 42,469 (9.5%) received XARELTO, 242,876 (54.5%) received aspirin, and 59,727 (13.4%) received enoxaparin.
  • After controlling for potential confounding factors, patients who received XARELTO after THA had a higher risk of combined prothrombotic (P=0.775) and bleeding (P<0.001) outcomes than those who received aspirin. However, XARELTO was associated with a lower risk of combined prothrombotic (P=0.036), but a higher risk of combined bleeding (P<0.001) outcomes than enoxaparin.
• Data regarding the 90-day risk of postoperative prothrombotic complications and bleeding events with XARELTO vs aspirin and enoxaparin in patients who underwent TKA are summarized in Table: Differences in the Risk of 90-Day Outcomes With XARELTO vs Aspirin and XARELTO vs Enoxaparin in Patients Who Underwent TKA.
• Data regarding the 90-day risk of postoperative prothrombotic complications and bleeding events with XARELTO vs aspirin and enoxaparin in patients who underwent THA are summarized in Table: Differences in the Risk of 90-Day Outcomes With XARELTO vs Aspirin and XARELTO vs Enoxaparin in Patients Who Underwent THA.

Highcock et al (2020)¹⁷ conducted a prospective cohort study to evaluate the efficacy and safety of XARELTO, dabigatran, and apixaban in patients who underwent THA and TKA.

• Overall, 2431 patients were included, of whom 911 received dabigatran (October 1, 2011 to April 30, 2012), 720 received apixaban (June 1, 2013 to January 1, 2014), and 800 received XARELTO (January 2, 2015 to November 10, 2015).
• Overall, 1127 and 1304 patients underwent THA and TKA, respectively.
• A statistically significant reduction in VTE was observed in the XARELTO group vs the dabigatran group (0.8% vs 3%; P<0.01) and the apixaban group (0.8% vs 2.1%; P<0.01).
  • A lower rate of symptomatic DVT was observed in the XARELTO group vs the dabigatran group (0.3% vs 2.2%; relative risk [RR], 0.11; 95% CI, 0.03-0.49; P<0.01) and the apixaban group (0.3% vs 0.8%; RR, 0.30; 95% CI, 0.06-1.48; P=0.14).
  • A low rate of symptomatic PE was observed in the XARELTO (0.5%), dabigatran (0.8%), and apixaban (1.3%) groups.
• Major bleeding in the XARELTO vs dabigatran vs apixaban group was observed in 1.4% vs 1.2% vs 0.8% of patients, respectively.
• Wound problems in the XARELTO vs dabigatran vs apixaban group were observed in 2.8% vs 1.1% vs 3.6% of patients, respectively.

Ní Cheallaigh et al (2020)¹⁸ conducted a retrospective cohort study to evaluate the efficacy and safety of aspirin compared with enoxaparin or XARELTO for the prevention of VTE following hip and knee replacement surgery.

• All patients who underwent elective primary TKR or THR in a large orthopedic hospital in Ireland between January 1, 2010 and June 30, 2016, were included.
• VTE rates in the 6 months following surgery were compared between patients receiving extended aspirin and those receiving inpatient enoxaparin or a modified XARELTO regimen (enoxaparin 40 mg once daily initiated 12 hours postoperatively for 3 doses followed by XARELTO 10 mg once daily for 14 days [TKR] or 35 days [THR]).
• Of the 6945 patients admitted during the study period, 6548 were eligible for inclusion. The mean age was 65.4 years, the mean body mass index was 30.3 kg/m², 55.3% of patients were female, and 55.8% underwent THR.
• The overall VTE rate was 0.99% (65/6548). The VTE rate in both the inpatient enoxaparin group (n=961) and extended aspirin group (n=3460) was 1.04%, while the VTE rate in the modified XARELTO group (n=1212) was 0.66% (P=0.154).
• A noninferiority analysis showed the extended aspirin regimen to be equivalent to the modified XARELTO regimen (unadjusted VTE risk difference comparing the extended aspirin regimen to the modified XARELTO regimen was 0.38%).
• A history of VTE was the only significant demographic risk factor for postoperative VTE (0.87% vs 3.54%; P=0.0002).

Kim et al (2019)¹⁹ conducted a nationwide claims database analysis to evaluate the efficacy and safety of XARELTO vs aspirin as thromboprophylaxis in real-world Korean patients who underwent hip arthroplasty.

• Patients aged ≥18 years with ≥1 hip arthroplasty (including total and partial hip replacements and hip replacement revisions) during the period of July 2009 to June 2013 were identified from the Health Insurance Review and Assessment (HIRA) claims database.
• Patients were 1:1 propensity score-matched (aspirin, n=2071; XARELTO, n=2071) to minimize selection bias and potential confounding factors.
• In the aspirin cohort, 65.7% of patients received >3-week treatment; in the XARELTO cohort, 31.7% received >3-week treatment.
• Aspirin was associated with a significantly higher incidence of overall VTE within 90 days after surgery compared with XARELTO (1.6% vs 0.6%; RR reduction, 59.4%; P<0.004).
  • DVT occurred more frequently with aspirin than with XARELTO (1.3% vs 0.5%; P<0.013), but PE occurred at similar rates between the 2 groups.
• Major bleeding events were similar among XARELTO- and aspirin-treated patients (2.1% vs 1.9%, respectively; P=0.579).

POST-MARKETING SAFETY SURVEILLANCE

Kwong et al (2017)²⁰ conducted an interim analysis at 2.5 years of an ongoing, 5-year, observational, retrospective, postmarketing safety surveillance study utilizing the United States Department of Defense healthcare database to evaluate major bleeding in patients who had undergone THR or TKR and were treated with XARELTO postoperatively.

• Patients who had received a THR, TKR, or both between January 1, 2013, to June 30, 2015, with incident XARELTO exposure within 2 days prior to surgery through the respective guideline-recommended length of treatment were included.
• Of the 12,429 XARELTO users identified during the 2.5-year study period who received THR and/or TKR surgery, 9 users experienced the primary efficacy outcome of major bleeding (2 after THR and 7 after TKR) based on the Cunningham algorithm. The bleeding incidence proportion in those with THR only was 0.05% (95% CI, 0.0-0.12) and was 0.09% (95% CI, 0.02-0.16) for those with TKR only.
• Based on exploratory analyses of inpatient secondary diagnosis codes or emergency department visits, the incidence proportion of clinically relevant bleeds (not considered major bleeding events in primary analysis) was 0.46% (95% CI, 0.34-0.58) and 0.21% (95% CI, 0.13-0.29), respectively.
• Major bleeding patients were more likely to be younger than those without major bleeding (63.1 vs 67.3 years) and male (55.6% vs 43.2%). Comorbidities were more prevalent in the major bleeding cohort compared with the nonmajor bleeding group. The most commonly reported comorbidities were hypertension (77.8% vs 53.6%) and coronary heart disease (44.4% vs 10.9%).
• No patients experienced a fatal outcome while hospitalized.
• This was a retrospective study using data originally collected for electronic medical record and accounting/claims purposes. Study results of major bleeding incidence rates and comparisons between major bleeding and nonmajor bleeding patients are limited by the small representation of major bleeding events, use of pharmacy records that capture drug dispensing information rather than actual administration of the drug, varying surgeon skill, and inherent limitations of the databases.

Tamayo et al (2014)²¹ conducted a retrospective, observational study evaluating longitudinal safety data of XARELTO in patients undergoing THR and/or TKR procedures. The data presented below represents the first 18 months (January 2013 - June 2014) of this ongoing, 5-year observational study.

• Of the 7977 patients evaluated in the THR/TKR cohort, 3 (0.04%; 95% CI, 0-0.09) experienced a major bleeding event, of which 1 (33.3%) had a gastrointestinal hemorrhage and 2 (66.6%) had unspecified major bleeding. There were no reported deaths.
• In the THR/TKR cohort, the mean age of those who experienced major bleeding was higher than those that did not bleed (70.7 and 66.7 years for major and nonmajor bleeding, respectively).

LITERATURE SEARCH

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, Derwent^® (and/or other resources, including internal/external databases) was conducted on 08 April 2026.