Summary

• Two randomized double-blind studies (RECORD1 and RECORD2) compared the efficacy and safety of oral XARELTO 10 mg once daily to enoxaparin 40 mg subcutaneous (SC) once daily for venous thromboembolism (VTE) prevention in patients undergoing total hip arthroplasty (THA).^1-3
• In RECORD1, the primary efficacy endpoint (composite of any deep vein thrombosis [DVT], nonfatal pulmonary embolism [PE], and all-cause mortality) occurred in 1.1% of patients receiving XARELTO compared to 3.7% of patients receiving enoxaparin, (P<0.001). The rate of major bleeding was similar in both groups (0.3% with XARELTO vs 0.1% with enoxaparin; P=0.18).²
• In RECORD2, the primary efficacy endpoint (composite of any DVT, nonfatal PE, and allcause mortality) occurred in 2% of patients receiving the extended regimen (ie, 5 weeks) of XARELTO compared to 9.3% of patients receiving the short-term regimen (ie, 2 weeks) of enoxaparin, (P<0.0001). Major bleeding occurred in 0.1% of patients in both treatment groups.³
• A randomized controlled trial (RCT) evaluated the efficacy and safety of XARELTO and aspirin 100 mg twice daily (BID) in the prevention of VTE in patients undergoing THA.⁴
  • The Doppler DVT rate was not statistically significant in the aspirin vs XARELTO groups (8.8% vs 8.3%; P=0.91).
  • Major bleeding events were reported in 2.9% of patients in the aspirin group and 8.3% of patients in the XARELTO group.
• A randomized, double-blind, controlled trial (EPCAT II) compared the efficacy and safety of XARELTO 10 mg once daily to aspirin 81 mg once daily for extended VTE prophylaxis in patients undergoing total knee replacement (TKR) or total hip replacement (THR). Patients received an initial daily dose of XARELTO 10 mg for 5 days postop then randomized to continue XARELTO 10 mg daily or switch to aspirin 81 mg daily for an additional 30 days for hip arthroplasty.⁵
  • Patients having THA saw DVT or PE in 0.55% (5/905) in the XARELTO group and 0.44% (4/902) in the aspirin group (P=1.00).
  • Major bleeding in the total hip subgroup was 0.33% in the XARELTO group and 0.33% in the aspirin group (P=1.00).
• A systematic review and network meta-analysis of 61 articles evaluated the efficacy of anticoagulants for VTE prevention after THA or TKA. The results showed that XARELTO had better efficacy for DVT prevention than dabigatran (relative risk [RR], 0.58; 95% confidence interval [CI], 0.49-0.69), low-molecular-weight heparin (LMWH; RR, 0.57; 95% CI, 0.50-0.65), aspirin (RR, 0.55; 95% CI, 0.39-0.77), unfractionated heparin (UFH; RR, 0.52; 95% CI, 0.43-0.64), and warfarin (RR, 0.32; 95% CI, 0.250.40).⁶
• A systematic review and meta-analysis of 11 randomized controlled trials compared the efficacy and safety of XARELTO with those of enoxaparin for thromboprophylaxis after THA. XARELTO-treated patients showed a significantly lower risk of total VTE and all-cause mortality (pooled risk ratio, 0.58; 95% CI, 0.34-0.99) than enoxaparin-treated patients.⁷
• A systematic review and network meta-analysis of 25 randomized controlled trials compared the efficacy and safety of new oral anticoagulants (NOACs) with those of nonNOACs for VTE prophylaxis after THA and TKA. The results showed that XARELTO was superior to non-NOACs (RR, 0.56; 95% CI, 0.38-0.81) and more effective than dabigatran (RR, 2.31; 95% CI, 1.31-4.06) for VTE prevention.⁸
• A systematic review and meta-analysis of 8 randomized controlled trials compared the efficacy and safety of XARELTO with those of enoxaparin for VTE prevention after THA or TKA. The results showed that XARELTO-treated patients had significantly lower rates of major VTE (P=0.009) and DVT (P<0.0001) than enoxaparin-treated patients.⁹
• An additional RCT,¹⁰ pooled and meta-analyses,^8,9,11-25 and observational, retrospective, cohort studies^26-31 identified during a literature search are included in the REFERENCES section for your review.

CLINICAL STUDIES

RECORD Studies

As part of the phase 3 RECORD (REgulation of Coagulation in ORthopaedic surgery to prevent Deep vein thrombosis and pulmonary embolism) program, RECORD1² and RECORD2³ assessed the efficacy and safety of oral XARELTO 10 mg once daily relative to enoxaparin 40 mg SC once daily for VTE prevention in patients undergoing elective THA. XARELTO was started 6 to 8 hours after surgery. Enoxaparin was started 12 hours before surgery and restarted 6 to 8 hours after wound closure. Efficacy and safety outcomes were the same for both trials.

Efficacy and Safety Endpoints for the RECORD Studies

Efficacy Outcomes

• Primary efficacy outcome: DVT, nonfatal PE, all-cause mortality
• Main secondary efficacy outcome: major VTE (proximal DVT, nonfatal PE, and VTE-related mortality)
• Other efficacy outcomes: symptomatic VTE during treatment and follow-up, DVT (any, proximal, distal)

Safety Outcomes

• Primary safety outcome: major bleeding starting after the first blinded dose and up to 2 days after last dose
  • Bleeding that was fatal, into a critical organ, required re-operation
  • Clinically overt extra-surgical site bleeding associated with a fall in hemoglobin of ≥2 g/dL or the infusion of ≥2 units of blood
• Other safety outcomes: Any bleeding*, nonmajor bleeding*, hemorrhagic wound complications*, cardiovascular adverse events, liver enzyme levels (*occurring between start of treatment and up to 2 days after last dose [“on-treatment”])

RECORD1

RECORD1² evaluated the efficacy and safety of oral XARELTO 10 mg once daily compared to enoxaparin 40 mg SC once daily for extended VTE prophylaxis in patients undergoing elective THA. Placebo tablets or injection were also administered. Treatments were administered for an average of 35 days (range, 31 to 39). Bilateral venography was performed 1 day after the last dose of study drug (ie, day 36 [range 32 to 40]), or earlier if the patient was symptomatic. Patients returned for a follow-up visit 30 to 35 days after the last dose of study drug.

• Primary efficacy analysis was to test for noninferiority in the per-protocol population and for superiority in the modified intent-to-treat (mITT) population.
  • The per-protocol population included those patients who had no major protocol violations.
  • The mITT population consisted of patients who had undergone surgery, had taken the study drug, and who had an adequate VTE assessment.
• A total of 4541 patients were randomized: 3029 were included in the per-protocol population (XARELTO, n=1537; enoxaparin, n=1492); 3153 were included in the mITT population (XARELTO, n=1595; enoxaparin, n=1558).
• Results demonstrated that XARELTO was significantly more effective than enoxaparin for prevention of VTE (see Table: Efficacy Results for RECORD1).
• There were no significant differences in bleeding rates between both groups (see Table: Safety Results for RECORD1).
  • Adverse event rates between XARELTO and enoxaparin were similar. Death during the active treatment period occurred in 4 patients in each treatment group.
  • Cardiovascular events (eg, cardiovascular death, myocardial infarction, ischemic stroke) were similar between treatment groups.
  • Increases in alanine aminotransferase (ALT) levels greater than 3 times the upper limit of normal (ULN) were reported in 2.0% (43/2128) of XARELTO-treated patients and 2.7% (57/2129) of enoxaparin-treated patients. All the abnormal enzyme elevations resolved by the end of the follow-up period.
• XARELTO was significantly more effective for extended thromboprophylaxis (5 weeks) than enoxaparin in patients undergoing THA. Both treatments had similar rates of bleeding and other adverse events.

RECORD2

RECORD2 evaluated the efficacy and safety of an extended thromboprophylaxis regimen of oral XARELTO 10 mg once daily compared to a short-term thromboprophylaxis regimen of SC injections of enoxaparin 40 mg once daily. XARELTO was given for a total 31 to 39 days; patients also received placebo SC injections for 10 to 14 days. Enoxaparin was administered for 10 to 14 days and placebo tablets were administered for 31 to 39 days. Bilateral venography was performed 1 day after the last dose of study medication (ie, day 32 to 40). Patients returned for a follow-up visit 30 to 35 days after the last dose of study drug.³

• The objective was to determine whether 5 weeks of prophylaxis with XARELTO was superior to 2 weeks of prophylaxis with enoxaparin, assessed in the mITT population (defined as patients who received 1 dose of study drug, had undergone planned surgery and had an adequate VTE assessment).
• A total of 2509 patients were randomized: 1733 patients (XARELTO, n=864; enoxaparin, n=869) were included in the mITT population for primary efficacy.
• Extended prophylaxis with XARELTO was significantly more effective than short-term prophylaxis with enoxaparin for prevention of VTE (see Table: Efficacy Results for RECORD2).
  • The primary efficacy outcome occurred in 17/864 patients receiving the extended regimen of XARELTO (2.0%; 95% CI, 1.2-3.1) compared to 81/869 patients receiving the short-term regimen enoxaparin (9.3%; 95% CI, 7.5-‍11.5), constituting an absolute risk reduction (ARR) of 7.3% (P<0.0001).
  • The secondary efficacy outcome of major VTE occurred in 6/961 patients receiving XARELTO (0.6%; 95% CI, 0.2-1.4) compared to 49/962 patients receiving enoxaparin (5.1%; 95% CI, 3.8-6.7), constituting an ARR of 4.5% (P<0.0001).
• Bleeding rates were similar for patients receiving extended thromboprophylaxis with XARELTO compared to those receiving short-term thromboprophylaxis with enoxaparin (see Table: Safety Results for RECORD2).
  • Major bleeding occurred in <0.1% of patients receiving XARELTO and enoxaparin. Requirements for blood transfusions and the amount of blood transfused were comparable between treatment groups.
  • Adverse event rates between patients receiving long-term thromboprophylaxis with XARELTO and those receiving short-term thromboprophylaxis with enoxaparin were similar. Death during the active treatment period occurred in 2 patients receiving XARELTO (both due to cardiovascular causes) and 6 patients receiving enoxaparin (1 due to PE, 4 unrelated to VTE, and 1 unexplained).
  • Cardiovascular events were similar between treatment groups.
  • Increases in ALT levels greater than 3 times the ULN was reported in 1.6% (19/1167) of XARELTO-treated patients and 4.7% (55/1164) of enoxaparintreated patients. All the abnormal enzyme elevations occurring with XARELTO resolved by the end of the follow-up period.
• Extended thromboprophylaxis with XARELTO was significantly more effective than shortterm thromboprophylaxis with enoxaparin plus placebo for prevention of VTE in patients undergoing elective THA, with similar safety and bleeding rates.

Prospective RCT Conducted in Chinese Patients

Ren et al (2021)⁴ conducted an RCT to evaluate the efficacy and safety of XARELTO and aspirin 100 mg BID in the prevention of VTE in patients undergoing THA.

• A total of 70 patients who underwent THA between January 2019 and 2020 were included, of whom 36 received XARELTO and 34 received aspirin.
• Adult patients undergoing unilateral primary THA with ≥1 week of aspirin cessation before surgery were eligible. Exclusion criteria included patients with a history of VTE, active malignancy, known prothrombotic conditions, or those requiring extended antithrombotic therapy for pre-existing conditions.
• Patient characteristics at baseline were similar in both XARELTO and aspirin groups.

Primary Outcomes

• The Doppler DVT rate was not statistically significant in the aspirin vs XARELTO group (8.8% vs 8.3%; P=0.91).
• The median total blood loss was not statistically significant in the aspirin vs XARELTO group (944.9 mL [interquartile range (IQR), 658.5-1137.8 mL] vs 978.3 mL [IQR, 747.41740.6 mL]; P=0.12).

Secondary Outcomes

• The median Harris score on postoperative day 30 or day 90 was not statistically significant in the aspirin vs XARELTO group (day 30, 81.0 [IQR, 78.8-83.0] vs 81.0 [IQR, 79.3-83.0]; P=0.67; day 90, 90.0 [IQR, 89.0-92.0] vs 91.5 [IQR, 88.3-92.8]; P=0.44).
• Complications within postoperative day 90 in the aspirin vs XARELTO groups included gastrointestinal adverse events (2.9% vs 5.6%; P=0.29), bleeding events (2.9% vs 8.3%; P=0.33), DVT events (8.8% vs 8.3%; P=0.91), systematic complications (0% vs 2.8%; P=0.33), and wound complications (2.9% vs 0%; P=0.30).

Postmarketing Study

EPCAT II

EPCAT II (Extended Venous Thromboembolism Prophylaxis Comparing XARELTO to Aspirin Following Total Hip and Knee Arthroplasty II), a randomized, double-blind, controlled study, evaluated the efficacy and safety of extended VTE prophylaxis in patients undergoing TKR or THR. XARELTO 10 mg once daily was compared to aspirin 81 mg once daily after XARELTO 10 mg was given once daily for 5 days postop.⁵

• A total of 3424 patients were enrolled, 1620 patients underwent total knee arthroplasty (TKA) and 1804 underwent THA. Both subgroups were followed for 90 days.
• All patients were initially dosed with XARELTO 10 mg once daily for 5 days postop then randomized to continue XARELTO 10 mg once daily or switched to aspirin 81 mg once daily for 9 days if having TKA or 30 days if having THA.
• Patients undergoing elective unilateral primary or revision knee or arthroplasty were eligible. Taking long-term aspirin at a dose of less than 100 mg per day was permitted. Exclusion criteria included hip or lower limb fracture in the previous 3 months, metastatic cancer, creatinine clearance <30 mL/min, and the need for long-term anticoagulation.^5,32
• Characteristics of the patients at baseline were similar in both XARELTO and aspirin groups.

Primary Outcomes

• DVT or PE, the primary efficacy endpoint, was similar in both groups, 0.70% (12/1717) in the XARELTO group and 0.64% (11/1707) in the aspirin group (0.06%; 95% CI, -0.55 to 0.66). Aspirin was found to be noninferior (P<0.001) but not superior (P=0.84).
  • Patients having TKA experienced DVT or PE in 0.86% (7/815) in the XARELTO group and 0.87% (7/805) in the aspirin group (P=1.00).
  • Patients having THA experienced DVT or PE in 0.55% (5/905) in the XARELTO group and 0.44% (4/902) in the aspirin group (P=1.00).
• Major bleeding was 0.29% in the XARELTO group and 0.47% in the aspirin group (difference, 0.18%; 95% CI -0.65 to 0.29, P=0.42) and clinically important bleeding was 0.99% in the XARELTO group and 1.29% in the aspirin group (difference, 0.30%; 95% CI -1.07 to 0.47, P=0.43).
  • Major bleeding in the total knee subgroup was 0.25% in the XARELTO group and 0.62% in the aspirin group (P=0.29).
  • Major bleeding in the total hip subgroup was 0.33% in the XARELTO group and 0.33% in the aspirin group (P=1.00).

Systematic Reviews and Meta-Analyses

Huang et al (2023)⁶ conducted a systematic review and network meta-analysis of 61 articles to evaluate the efficacy of anticoagulants for VTE prevention after THA or TKA.

• The following 11 anticoagulants were included in the analysis: XARELTO, apixaban, aspirin, betrixaban, dabigatran, darexaban, edoxaban, fondaparinux, LMWH, UFH, and warfarin.
• The DVT outcome was assessed using 61 articles containing 67 studies.
  • XARELTO (P=0.731) showed better efficacy for DVT prevention than dabigatran (RR, 0.58; 95% CI, 0.49-0.69; P=0.392), LMWH (RR, 0.57; 95% CI, 0.50-0.65; P=0.358), aspirin (RR, 0.55; 95% CI, 0.39-0.77; P=0.310), UFH (RR, 0.52; 95% CI, 0.430.64; P=0.233), and warfarin (RR, 0.32; 95% CI, 0.250.40; P=0.033).
• Safety results were not provided.

Wang et al (2023)⁷ conducted a systematic review and meta-analysis of 11 randomized controlled trials to compare the efficacy and safety of XARELTO with those of enoxaparin for thromboprophylaxis after THA.

• Overall, 9057 patients were included in the analysis, with sample sizes ranging from 262209 and 26-2224 in the XARELTO and enoxaparin groups, respectively.
  • The age ranges in the XARELTO and enoxaparin groups were 42.9-67.0 and 40.165.6 years, respectively.
  • Patients were prescribed a standard dose of 40 mg enoxaparin in all the studies and a standard dose of 10 mg XARELTO in the majority of the studies, except 3 that used varying XARELTO doses ranging from 5 to 40 mg.
• Overall, 11 studies reported VTE, all-cause mortality, and DVT events, 8 studies reported major VTE events, and 7 studies reported symptomatic VTE events in patients receiving XARELTO or enoxaparin after THA.
  • XARELTO-treated patients showed a significantly lower risk of total VTE and all-cause mortality (pooled risk ratio, 0.58; 95% CI, 0.34-0.99), major VTE (pooled risk ratio, 0.37; 95% CI, 0.150.90), and symptomatic VTE (pooled risk ratio, 0.51; 95% CI, 0.300.87; I²=0%) than enoxaparin-treated patients. However, no significant difference was observed between the treatment groups in terms of DVT (pooled risk ratio, 0.57; 95% CI, 0.32-1.02).
• Overall, 10 studies reported major bleeding and total bleeding events, 9 studies reported clinically relevant nonmajor bleeding (CRNMB) events, 4 studies reported drugrelated adverse events, and 8 studies reported minor bleeding events and wound infection rates in patients receiving XARELTO or enoxaparin after THA.
  • No significant differences were observed between the treatment groups in terms of major bleeding events (pooled risk ratio, 1.18; 95% CI, 0.77-1.80; I²=0%), total bleeding events (pooled risk ratio, 1.12; 95% CI, 0.93-1.34; I²=8.1%), CRNMB events (pooled risk ratio, 1.22; 95% CI, 0.93-1.61; I²=1.1%), minor bleeding events (pooled risk ratio, 0.97; 95% CI, 0.76-1.23; I²=0%), drug-related AEs (pooled risk ratio, 0.99; 95% CI, 0.87-1.12; I²=0%), and wound infection rates (pooled risk ratio, 1.11; 95% CI, 0.58-2.14; I²=0%).

Alfarhan (2022)²² conducted a systematic review and meta-analysis of 9 RCTs that investigated the clinical efficacy and safety of enoxaparin compared with newer oral anticoagulants, including XARELTO, in the prevention of VTE in patients who underwent THR (N=24,584; XARELTO, n=5137).

• A reduction in the risk of symptomatic VTE was observed with XARELTO compared with enoxaparin (RR, 0.46%; 95% CI, 0.32-0.77; P=0.001).
• A reduction in the risk of symptomatic DVT was observed with XARELTO compared with enoxaparin (RR, 0.42%; 95% CI, 0.24-0.69; P<0.05), while a nonsignificant trend was observed for symptomatic PE (RR, 0.87%; 95% CI, 0.34-2.53; P=0.78).
• XARELTO also reduced the risk of total VTE or all-cause fatality (RR, 0.54%; 95% CI, 0.400.82; P<0.05) and major VTE or VTE-related mortality (RR, 0.39%; 95% CI, 0.190.80; P<0.05).
• In comparison with enoxaparin, there was no association between the varying risks of symptomatic PE (RR, 0.67%; 95% CI, 0.32-1.45; P=0.29) or DVT (RR, 0.84%; 95% CI, 0.21-3.61; P=0.79) and XARELTO.
• A non-significant trend towards an increase in the risk of clinically relevant bleeding (RR, 1.23%; 95% CI, 1.03-1.48; P=0.37) and major bleeding was observed with XARELTO compared with enoxaparin.
• Based on an indirect comparison between XARELTO, apixaban, and dabigatran, a reduced risk of VTE was observed with XARELTO (Table: Indirect Comparisons Between XARELTO, Apixaban, and Dabigatran).

Yi et al (2022)⁸ conducted a systematic review and network meta-analysis of 25 randomized controlled trials to compare the efficacy and safety of NOACs with those of nonNOACs for VTE prophylaxis after THA and TKA.

• Overall, 42,994 patients were included in the analysis, of whom 22,882 and 20,112 were in the NOAC (including XARELTO [n=11], apixaban [n=4], dabigatran [n=7], edoxaban [n=3], and betrixaban [n=1]) and non-NOAC (including placebo [n=1], enoxaparin [n=19], nadroparin [n=1], aspirin [n=3], and TB-402 [n=1]) groups, respectively.
  • The mean age was 64.06 years, and 59.92% of patients were female.
• XARELTO was superior to non-NOACs (RR, 0.65; 95% CI, 0.52-0.81) and more effective than dabigatran (RR, 2.28; 95% CI, 1.26-4.12) for DVT prevention.
• Results from a direct comparison of the efficacy and safety outcomes between XARELTO and non-NOACs are summarized in Table: Efficacy and Safety Outcomes Between XARELTO and Non-NOACs.
• Results from a network comparison of the efficacy and safety outcomes among different NOACs are summarized in Table: Efficacy and Safety Outcomes Among Different NOACs.

Xu et al (2022)⁹ conducted a systematic review and meta-analysis of 8 randomized controlled trials to compare the efficacy and safety of XARELTO with those of enoxaparin for VTE prevention after THA or TKA.

• Overall, 13,384 patients were included in the analysis, of whom 6629 received XARELTO and 6755 received enoxaparin.
  • The median age was 70.9 years, and 60.8% and 59.3% of patients were female in the XARELTO and enoxaparin groups, respectively.
  • Patients were initiated on XARELTO 10 mg once daily and progressed to twice daily doses for 539 days. Similarly, patients were prescribed enoxaparin ranging from 30 to 40 mg either once or twice daily for 5-39 days.
  • The follow-up duration was 9-75 days.
• Overall, 8 studies reported major VTE and DVT events in patients receiving XARELTO or enoxaparin after THA or TKA.
  • XARELTO resulted in significantly lower rates of major VTE (RR, 0.40; 95% CI, 0.200.80; I²=67%; P=0.009) and DVT (RR, 0.49; 95% CI, 0.34-0.69; I²=76%; P<0.0001) than enoxaparin.
• Overall, 8 studies reported major bleeding, any bleeding, and transfusion events in patients receiving XARELTO or enoxaparin after THA or TKA.
  • No significant difference was observed between the treatment groups in terms of major bleeding (RR, 1.62; 95% CI, 0.91-2.89; I²=0%; P=0.1), any bleeding (RR, 1.10; 95% CI, 0.97-1.24; I²=0%; P=0.14), and transfusion events (RR, 1.04; 95% CI, 0.97-1.10; I²=56%; P=0.27).
• Overall, 4 studies reported all-cause mortality events, 8 studies reported wound complications, and 5 studies reported reoperation rates in patients receiving XARELTO or enoxaparin after THA or TKA.
  • No significant difference was observed between the treatment groups in terms of allcause mortality events (RR, 0.79; 95% CI, 0.35-1.77; I²=0%; P=0.57), wound complications (RR, 0.98; 95% CI, 0.75-1.27; I²=0%; P=0.87), and reoperation rates (RR, 1.94; 95% CI, 0.81-4.60; I²=0%; P=0.14).

Feng et al (2021)²⁰ conducted a systematic review and meta-analysis of 53 RCTs that ranked the efficacy and safety of 19 anticoagulants, including XARELTO, in the prevention of VTE in patients who underwent TKA or THA (N=45,067).

• XARELTO was effective in preventing VTE as compared with enoxaparin (risk difference [RD], 0.07; 95% credible interval, 0.06-0.08).
• XARELTO tended toward an increased risk of bleeding as compared with enoxaparin (RD, 0.00; 95% credible interval, -0.01 to 0.00).

Hu et al (2021)²¹ conducted a meta-analysis of 7 studies (5 RCTs and 2 retrospective studies) to determine the efficacy and safety of aspirin compared with XARELTO for the prevention of VTE in patients who underwent TKA, THA, or hip fracture surgery.

• In 6 studies, a statistically significant difference in postoperative VTE was not observed in the XARELTO vs aspirin group (39 vs 53 events; RR, 0.75; 95% CI, 0.501.11; P=0.15).
• In 4 studies, a statistically significant difference in major bleeding was not observed in the XARELTO vs aspirin group (12 vs 11 events; RR, 0.94, 95% CI, 0.45-2.37; P=0.94).
• In 5 studies, the incidence of nonmajor bleeding was higher in the XARELTO vs aspirin group (120 vs 95 events; RR, 1.29; 95% CI, 1.05-1.58; P=0.02).
• In 2 studies, no difference in mortality was observed in the XARELTO vs aspirin group
  (1 vs 1 death; RR, 0.88; 95% CI, 0.12-6.44; P=0.90).

Liu et al (2019)³³ conducted a systematic review and meta-analysis of 13 randomized, controlled trials to determine the efficacy and safety of XARELTO (10 mg once daily) for prevention of thrombotic events following THA and TKA.

• Of the 13 randomized, controlled trials, 6 included patients that underwent THA, 5 included patients that underwent TKA, and 2 included patients that underwent either THA or TKA.
• The overall rates of VTE events, DVT, PE, and death were 1%, 6%, <1%, and <1%, respectively, for patients receiving treatment with XARELTO following THA and TKA.
• A subgroup analysis demonstrated that XARELTO had superior effects in THA patients (THA subgroup, incidence of DVT: 4%; TKA subgroup, incidence of DVT: 8%).
• A pooled analysis of bleeding events showed that the overall rates of major bleeding events (bleeding that was fatal, occurred in a critical organ, or required additional surgeries, or clinically overt bleeding that was associated with a drop in hemoglobin of ≥2 g/dL or resulted in transfusion of ≥2 units of blood) and nonmajor bleeding events were <1% and 3%, respectively.

LITERATURE SEARCH

A literature search of OVID MEDLINE^®, Embase^®, BIOSIS Previews^®, Derwent Drug File (and/or other resources, including internal/external databases) pertaining to this topic was conducted on 21 May 2024.