We examined the risk of thrombotic and major bleeding events in patients undergoing total hip and knee replacement (THR and TKR) treated with thromboprophylaxis, using nationwide population-based databases. We identified 83 756 primary procedures performed between 1997 and 2011. The outcomes were symptomatic venous thromboembolism (VTE), myocardial infarction (MI), stroke, death and major bleeding requiring hospitalisation within 90 days of surgery.

A total of 1114 (1.3%) and 483 (0.6%) patients experienced VTE and bleeding, respectively. The annual risk of VTE varied between 0.9% and 1.6%, and of bleeding between 0.4% and 0.8%. The risk of VTE and bleeding was unchanged over a 15-year period. A total of 0.7% of patients died within 90 days, with a decrease from 1% in 1997 to 0.6% in 2011 (p < 0.001). A high level of comorbidity and general anaesthesia were strong risk factors for both VTE and bleeding, with no difference between THR and TKR patients. The risk of both MI and stroke was 0.5%, which remained unchanged during the study period.

In this cohort study of patients undergoing THR and TKR patients in routine clinical practice, approximately 3% experienced VTE, MI, stroke or bleeding. These risks did not decline during the 15-year study period, but the risk of dying fell substantially.

Cite this article: Bone Joint J 2014;96-B:479–85.

Aims. We investigated the efficacy and safety profile of commonly used venous thromboembolism (VTE) prophylaxis agents following hip and knee arthroplasty. Methods. A systematic search of PubMed, Embase, Cochrane Library, Web of Science, and OrthoSearch was performed. Prophylaxis agents investigated were aspirin (< 325 mg and ≥ 325 mg daily), enoxaparin, dalteparin, fondaparinux, unfractionated heparin, warfarin, rivaroxaban, apixaban, and dabigatran. The primary efficacy outcome of interest was the risk of VTE, whereas the primary safety outcomes of interest were the risk of major bleeding events (MBE) and wound complications (WC). VTE was defined as the confirmed diagnosis of any deep vein thrombosis and/or pulmonary embolism. Network meta-analysis combining direct and indirect evidence was performed. Cluster rank analysis using the surface under cumulative ranking (SUCRA) was applied to compare each intervention group, weighing safety and efficacy outcomes. Results. Of 86 studies eligible studies, cluster rank analysis showed that aspirin < 325 mg daily (SUCRA-VTE 89.3%; SUCRA-MBE 75.3%; SUCRA-WC 71.1%), enoxaparin (SUCRA-VTE 55.7%; SUCRA-MBE 49.8%; SUCRA-WC 45.2%), and dabigatran (SUCRA-VTE 44.9%; SUCRA-MBE 52.0%; SUCRA-WC 41.9%) have an overall satisfactory efficacy and safety profile. Conclusion. We recommend the use of either aspirin < 325 mg daily, enoxaparin, or dabigatran for VTE prophylaxis following hip and knee arthroplasty. Cite this article: Bone Joint J 2024;106-B(9):924–934

Aims. The aim of this study is to compare the effectiveness and safety of thromboprophylactic treatments in patients undergoing primary total knee arthroplasty (TKA). Methods. Using nationwide medical registries, we identified patients with a primary TKA performed in Denmark between 1 January 2013 and 31 December 2018 who received thromboprophylactic treatment. We examined the 90-day risk of venous thromboembolism (VTE), major bleeding, and all-cause mortality following surgery. We used a Cox regression model to compute hazard ratios (HRs) with 95% confidence intervals (CIs) for each outcome, pairwise comparing treatment with dalteparin or dabigatran with rivaroxaban as the reference. The HRs were both computed using a multivariable and a propensity score matched analysis. Results. We identified 27,736 primary TKA patients who received thromboprophylactic treatment (rivaroxaban (n = 18,846); dalteparin (n = 5,767); dabigatran (n = 1,443); tinzaparin (n = 1,372); and enoxaparin (n = 308)). In the adjusted multivariable analysis and compared with rivaroxaban, treatment with dalteparin (HR 0.68 (95% CI 0.49 to 0.92)) or dabigatran (HR 0.31 (95% CI 0.13 to 0.70)) was associated with a decreased risk of VTE. No statistically significant differences were observed for major bleeding or all-cause mortality. The propensity score matched analysis yielded similar results. Conclusion. Treatment with dalteparin or dabigatran was associated with a decreased 90-day risk of VTE following primary TKA surgery compared with treatment with rivaroxaban. Cite this article: Bone Joint J 2021;103-B(10):1571–1577

The April 2023 Oncology Roundup. 360. looks at: Complete tumour necrosis after neoadjuvant chemotherapy defines good responders in patients with Ewing’s sarcoma; Monitoring vascularized fibular autograft: are radiographs enough?; Examining patient perspectives on sarcoma surveillance; The management of sacral tumours; Venous thromboembolism and major bleeding in the clinical course of osteosarcoma and Ewing’s sarcoma; Secondary malignancies after Ewing’s sarcoma: what is the disease burden?; Outcomes of distal radial endoprostheses for tumour reconstruction: a single centre experience over 15 years; Is anaerobic coverage during soft-tissue sarcoma resection needed?; Is anaerobic coverage during soft-tissue sarcoma resection needed?

The August 2023 Hip & Pelvis Roundup. 360. looks at: Using machine learning to predict venous thromboembolism and major bleeding events following total joint arthroplasty; Antibiotic length in revision total hip arthroplasty; Preoperative colonization and worse outcomes; Short stem cemented total hip arthroplasty; What are the outcomes of one- versus two-stage revisions in the UK?; To cement or not to cement? The best approach in hemiarthroplasty; Similar re-revisions in cemented and cementless femoral revisions for periprosthetic femoral fractures in total hip arthroplasty; Are hip precautions still needed?

The primary objective of this study was to establish a safety profile for an all-arthroscopic anatomic glenoid reconstruction via iliac crest autograft augmentation for the treatment of shoulder instability with glenoid bone loss. Short-term clinical and radiological outcomes were also evaluated. This study involved a retrospective analysis of prospectively collected data for 14 patients (male 8, female 6) who were treated for shoulder instability with bone loss using autologous iliac crest bone graft between 2014 and 2018. Of 14 patients, 11 were available for follow-up. The safety profile was established by examining intra-operative and post-operative complications such as neurovascular injuries, infections, major bleeding, and subluxations. Assessment of pre-operative and post-operative Western Ontario Shoulder Instability (WOSI) index, radiographs, and CT scans comprised the evaluation of clinical and radiological outcomes. A good safety profile was observed. There was no occurrence of intraoperative complications, neurovascular injuries, adverse events, or major bleeding. One patient did develop an infection in the neurovascular injuries, adverse events, or major bleeding. One patient did develop an infection in the treated shoulder post-surgery. There were no subluxations or positive apprehension tests on clinical examination post-operatively. Short-term clinical outcomes were seen to be favorable WOSI scores at the most recent follow-up were significantly higher than pre-operative scores, with a mean increase of 39.6 ± 10.60 (p = 0.00055). The average follow-up for CT scan was 4.66 (SD± 2.33) months, where all patients showed bone graft union. Arthroscopic treatment of shoulder instability with bone loss via autologous iliac crest bone graft is shown to be a safe operative procedure that results in favorable short-term clinical and radiological outcomes. Further investigations must be done to evaluate the longevity of these positive health outcomes

A once-daily dose of rivaroxaban 10 mg, an oral, direct Factor Xa inhibitor, was compared with enoxaparin 40 mg subcutaneously once daily for prevention of venous thromboembolism in three studies of patients undergoing elective hip and knee replacement (RECORD programme). A pooled analysis of data from these studies (n = 9581) showed that rivaroxaban was more effective than enoxaparin in reducing the incidence of the composite of symptomatic venous thromboembolism and all-cause mortality at two weeks (0.4% vs 0.8%, respectively, odds ratio 0.44; 95% confidence interval 0.23 to 0.79; p = 0.005), and at the end of the planned medication period (0.5% vs 1.3%, respectively; odds ratio 0.38; 95% confidence interval 0.22 to 0.62; p < 0.001). The rate of major bleeding was similar at two weeks (0.2% for both) and at the end of the planned medication period (0.3% vs 0.2%). Rivaroxaban started six to eight hours after surgery was more effective than enoxaparin started the previous evening in preventing symptomatic venous thromboembolism and all-cause mortality, without increasing major bleeding

Introduction. Rivaroxaban is the first licensed oral direct inhibitor of factor Xa. Recent studies from the RECORD trials suggest rivaroxaban has superior efficacy compared to enoxaparin in preventing venous thromboembolism (VTE) with no significant increase in the major bleeding risk. Concerns remain regarding the incidence of minor bleeding, consequent delayed wound healing and subsequent risk of infection. The aim of this observational study was to assess the incidence of post-operative complications in patients receiving either rivaroxaban or enoxaparin thromboprophylaxis following elective hip and knee arthroplasty. Methods. 258 patients undergoing elective total hip or knee arthroplasty within one NHS Trust were included. 202 subjects (mean age 70.7 years ± 10.0, 43% male) received a daily dose of 10mg of oral rivaroxaban and 56 (mean age 70.9 years ± 9.8, 39% male) had a daily subcutaneous injection of 40 mg of enoxaparin as thromboprophylaxis. Endpoints included VTE (deep vein thrombosis and pulmonary embolism), haemorrhagic wound complications, hospital re-admission, requirement for blood transfusion, minor and major bleeding and death. Results. There were no significant differences in the incidence of deep vein thrombosis, requirement for blood transfusion and readmission rate between rivaroxaban and enoxaparin-treated patients. However, the incidence of minor bleeding (2.0% versus 0%) and haemorrhagic wound complications (4.9% versus 1.8%) were non-significantly higher in the rivaroxaban-treated group. There were no cases of pulmonary embolism, major bleeding or death in either group. Conclusion. Our experience with rivaroxaban in elective hip and knee arthroplasty showed no significant difference in the incidence of VTE or major bleeding. There was, however, a tendency to greater risk of minor bleeding and consequent delayed wound healing affecting both morbidity and delaying discharge. These may predispose patients to a higher risk of wound infection, and thus these issues require further large scale evaluation

Hip and knee arthroplasty has been associated with relatively high rates of thromboembolic events and the majority of UK orthopaedic surgeons use at least one form of prophylaxis. Of the many different subgroups of thromboembolic rates that are commonly presented in the literature, symptomatic proximal deep vein thrombosis (spDVT) and fatal pulmonary embolism (fPE) are perhaps the most important clinical outcomes. To determine the effectiveness of common chemical and mechanical prophylactic methods in preventing spDVT and fPE in patients undergoing primary hip and knee arthroplasty. A systematic review of the literature from 1981 to December 2002 was performed. Predetermined inclusion and exclusion criteria were applied. Studies where more than one method of prophylaxis was used were excluded from analysis. For each individual method of prophylaxis, data was extracted, combined and converted to give estimates of the rates of spDVT, fPE and major bleeding events. Absolute risk reduction estimates for spDVT, fPE and major bleeding events were calculated by comparing the thromboembolic rates for each method of prophylaxis with using no prophylaxis of any kind. 992 studies were identified of which 162 met the inclusion criteria. No method of prophylaxis was statistically significantly more effective at preventing spDVT and fPE than using nothing. There were at least as many major bleeding complications as spDVTs. The number of fPEs prevented was very small. When complications such as major bleeding are considered, the evidence behind the use of any prophylaxis is unconvincing

Introduction: The standard length of hospital stay after total hip arthroplasty (THA) can be as short as 4 days. However, the risk of venous thromboembolism (VTE) extends beyond this period of hospitalization. A pooled analysis of the RECORD1 and RECORD2 studies evaluated the efficacy, safety, and timing of events with rivaroxaban compared with enoxaparin for the prevention of VTE after THA. Methods: Patients (N=7,050) were randomized to receive oral rivaroxaban 10 mg once daily starting postoperatively (for 31–39 days) or subcutaneous enoxaparin 40 mg once daily starting preoperatively (for 31–39 days in RECORD1, and 10–14 days followed by placebo in RECORD2). The primary efficacy endpoint was the composite of symptomatic VTE and all-cause mortality. The safety endpoints were treatment-emergent major bleeding, major bleeding including surgical-site bleeding, major bleeding plus clinically relevant non-major (CRNM) bleeding, and any bleeding. The primary efficacy endpoint was assessed during treatment. The incidence and timing of the safety endpoints were assessed after the first dose of study medication and up to 2 days after the last dose. Results: Rivaroxaban significantly reduced the incidence of symptomatic VTE and all-cause mortality compared with enoxaparin regimens (0.44% vs 1.01%, respectively; p=0.006), with no significant differences in major bleeding (0.2% vs 0.09%; p=0.219) or the composite of major plus CRNM bleeding (3.23% vs 2.61%; p=0.141). Of the symptomatic VTE and all-cause mortality events, 73% and 86% occurred after day 4 with the rivaroxaban and enoxaparin regimens, respectively. For the composite of major plus CRNM bleeding, 48% and 33% of events occurred after day 4 with the rivaroxaban and enoxaparin regimens, respectively. Conclusion: Rivaroxaban significantly reduced symptomatic VTE and all-cause mortality after THA compared with the enoxaparin regimens, with no significant difference in bleeding events. Major plus CRNM bleeding was more likely to occur earlier than day 4, whereas the majority of symptomatic venous thromboembolic events occurred after day 4. These results highlight the relevance of extended duration of thromboprophylaxis after THA as most VTE events occur post-discharge

Introduction: The risk of venous thromboembolism (VTE) remains a major concern beyond the standard period of hospitalization of about 4 days after total knee arthroplasty (TKA). A pooled analysis of the RECORD3 and RECORD4 studies evaluated the efficacy, safety, and timing of events with rivaroxaban compared with enoxaparin for the prevention of VTE after TKA. Methods: Patients (N=5,679) were randomized to receive oral rivaroxaban 10 mg once daily starting postoperatively or subcutaneous enoxaparin 40 mg once daily starting preoperatively (European Union regimen; RECORD3) or enoxaparin 30 mg every 12 hours starting postoperatively (North American regimen; RECORD4) for 10–14 days. The primary efficacy endpoint was the composite of symptomatic VTE and all-cause mortality, and this was analyzed over the treatment period. The safety endpoints were treatment-emergent major bleeding, major bleeding including surgical-site bleeding, major bleeding plus clinically relevant non-major (CRNM) bleeding, and any bleeding. The incidence and timing of the safety endpoints were assessed after the first dose of study medication and up to 2 days after the last dose. Results: Rivaroxaban significantly reduced symptomatic VTE and all-cause mortality compared with enoxaparin regimens (0.73% vs 1.71%, respectively; p=0.001) with no significant differences in major bleeding (0.62% vs 0.36%, p=0.185) or composite of major plus CRNM bleeding (3.13% vs 2.48%, p=0.145). The majority of venous thromboembolic events occurred after day 4 for both regimens (rivaroxaban: 70%; enoxaparin: 68%). For the composite of major plus CRNM bleeding events, 44% occurred after day 4 with rivaroxaban regimens and 38% occurred after day 4 with enoxaparin regimens. Conclusion: Rivaroxaban significantly reduced symptomatic VTE and all-cause mortality compared with enoxaparin regimens after TKA, with no significant difference in bleeding events between regimens. Major plus CRNM bleeding was more likely to occur before day 4, whereas the majority of symptomatic venous thromboembolic events occurred after day 4. These results highlight the importance of continuing thromboprophylaxis beyond the normal time of hospital discharge for TKA

Introduction: Four randomized, double-blind, phase III studies (RECORD1–4) investigated the oral, direct Factor Xa inhibitor rivaroxaban for the prevention of venous thromboembolism (VTE) after major orthopaedic surgery. Patients (N=12,729) were randomized to receive oral rivaroxaban 10 mg once daily or subcutaneous enoxaparin 40 mg once daily (RECORD1–3), or 30 mg twice daily (RECORD4). In RECORD1 and 2, patients undergoing total hip arthroplasty received rivaroxaban for 31–39 days. Enoxaparin was given for 31–39 days in RECORD1, 10–14 days followed by placebo in RECORD2. In RECORD3 and 4, patients undergoing total knee arthroplasty received prophylaxis for 10–14 days. After prophylaxis, all patients were followed up for a further 30–35 days. Rivaroxaban significantly reduced the incidence of the primary efficacy outcome for the individual studies (total VTE; composite of any deep vein thrombosis, non-fatal pulmonary embolism [PE] and all-cause mortality) compared with the enoxaparin regimens, with similar rates of major bleeding. Methods: A pre-specified pooled analysis of all four trials was performed on all randomized patients who received at least one dose of double-blind study medication to evaluate the effect of rivaroxaban on the composite of symptomatic VTE and all-cause mortality (primary outcome for pooled analysis), and bleeding. This outcome was analysed at day 12±2 in the active treatment pool (enoxaparin-controlled in all studies) and in the total study duration pool (including follow-up after treatment). Results: Rivaroxaban significantly reduced the incidence vs enoxaparin of the composite of symptomatic VTE and death (day 12±2: 0.47% vs 0.97%, respectively, p=0.001; total study duration: 0.81% vs 1.6%, respectively, p< 0.001) and the composite of PE and death (day 12±2: 0.19% vs 0.39%, respectively, p=0.049; total study duration: 0.47% vs 0.76%, respectively, p=0.039). The rates of major bleeding with the rivaroxaban and enoxaparin regimens were 0.34% and 0.21%, respectively, p=0.175 at day 12±2 and at total study duration were 0.44% and 0.27%, respectively, p=0.135. Rivaroxaban also reduced the composite of death, infarction, stroke, symptomatic VTE and major bleeding vs enoxaparin (total study duration: 1.6% vs 2.2%, respectively, p=0.006). Conclusion: Rivaroxaban reduced the composites of major clinical outcomes compared with enoxaparin regimens, with similar rates of major bleeding, in patients undergoing major orthopaedic surgery

Background: The recognised risk of post-operative venous thromboembolism (VTE), presenting as deep vein thrombosis (DVT) and/or pulmonary embolism (PE), after elective total hip and knee arthroplasty (THA and TKA) has always made the selection of suitable thromboprophylaxis treatment a clinical priority for orthopaedic surgeons. Over recent years there has been the emergence of new oral direct Factor Xa (FXa) inhibiting anticoagulants, which may replace the widely used low-molecular-weight heparins (LMWHs). Methods: A systematic review of published English-language literature (completed in July 2009) and surgical type meta-analyses were conducted to compare the efficacy (risk of any DVT, PE and all-cause mortality) and safety (risk of major bleeding requiring clinical intervention) of oral direct FXa inhibiting anticoagulants with LMWHs in THA and TKA. Results: Five eligible THA randomised-controlled trials (RCTs) with total of 9286 patients and three eligible TKA RCTs with 6917 patients were identified. The Der-Simonian-Laird random effects model was employed for each meta-analysis and heterogeneity between trials was explored statistically using the Mantel-Haenszel χ. 2. test. The efficacy meta-analysis of THA RCTs revealed an odds ratio (OR) 0.46 (95% confidence interval (c.i.) 0.23, 0.92), which was significantly (P = 0.03) in favour of the oral FXa inhibitors but there was sizable heterogeneity amongst trials (P = 0.0002). Although the safety meta-analysis of THA RCTs showed an increase incidence of major bleeding with the use of oral FXa inhibitors, OR 1.71 (95% c.i. 0.67, 4.39), this risk was not statistically significant (P = 0.26) with little heterogeneity between trials (P = 0.44). The efficacy meta-analysis of TKA RCTs demonstrated an efficacy OR 0.56 (95% c.i. 0.42, 0.73), in favour of the oral FXa inhibitors (P = 0.0001) with no significant heterogeneity (P = 0.21). The safety meta-analysis of TKA RCTs showed an increased occurrence of major bleeding with oral FXa inhibitors, OR 1.79 (95% c.i. 0.83, 3.87), but this was not statistically significant (P = 0.14) and heterogeneity between trials was low (P = 0.54). Conclusions: This review demonstrated an overall better efficacy for oral FXa inhibitors compared with LMWHs in thromboprophylaxis for both THA and TKA. Although it also revealed that oral FXa inhibitors were statistically as safe as LMWHs, there was clinically higher incidence of major bleeding with their use in both THA and TKA. These safety results coupled with the fact that currently no specific antidote exists, highlights the urgent need for further research and large RCTs to prove the clinical safety of all new oral direct FXa inhibiting anticoagulants

Thromboprophylaxis remains a controversial issue and many disagree about the optimum method or even if it is required at all. We present a new method of performing meta-analysis incorporating studies with both experimental and observational study designs. We have developed a model that compares study cohorts of several different methods of thromboprophylaxis with a simulated matched control group whose variance helps to adjust for bias. This allows meaningful comparisons between studies and treatments that have not been directly compared. We performed a systematic review of the literature from 1981 to October 2004. Studies where more than one method of prophylaxis was used were excluded from analysis. For each individual method of prophylaxis, data was extracted, combined and converted to give estimates of the rates of symptomatic, proximal DVT, fatal PE and major bleeding events. We identified 1242 studies of which 203 met the inclusion criteria for further analysis. This represented the results of over fifty thousand studied patients. We expressed the results for the different prophylactic methods as odds ratios compared to no prophylaxis. All methods showed a beneficial effect in reducing VTEs apart from stockings and aspirin which showed an increase in the number of PE events. These results are particularly interesting when viewed from the standpoint of an individual NHS hospital trust that performs around 500 hip and knee replacements per year. Over a 5 year period, the more effective methods of prophylaxis prevented between 15 and 40 symptomatic DVTs and up to 3 fatal PEs compared to no treatment. However, they cause between 8 and 40 more major bleeding events. We do not know the proportion of these major bleeding events that are fatal

Purpose:. Starting February 2012, our institution changed from enoxaparin (Lovenox) to the Factor Xa inhibitor, rivaroxaban (Xarelto) for venous thromboembolism prophylaxis after primary total hip (THA) and total knee arthroplasty (TKA). The purpose of our study was to compare rates of venous thromboembolism and rates of major bleeding between these two medications when used for venous thromboembolism prophylaxis after primary THA and TKA. Methods:. A retrospective review was performed on 1795 patients who underwent THA or TKA at our institution between January 1, 2011 and December 31, 2012. Patients were excluded if they had a bilateral procedure, partial arthroplasty (hip hemiarthroplasty, unicompartmental knee arthroplasty), revision surgery, and cases designated as complex. Patients were excluded if they were on other anticoagulants (dabigatran, aspirin, clopidogrel, warfarin, heparin, fondaparinux), or if pre-operative creatinine was 1.2 or greater. After excluding these patients, there were 1089 patients included in the study. Chart review recorded demographics (age, gender), comorbidities (BMI, ASA, creatinine), surgery performed (primary THA or TKA), length of stay (LOS), venous thromboembolic events (deep venous thrombosis [DVT], pulmonary embolus [PE]), post-operative infections, and major bleeding events (stroke, post-operative bleeding requiring transfusion). Periprosthetic infection rates are also currently being reviewed. T-tests were used to compare continuous variables between treatment groups, and Chi-square tests were used to compare categorical variables between treatment groups (α = 0.05). Results:. There were 779 patients (71.5%) who received enoxaparin and 310 patients (28.5%) who received rivaroxaban during the study period. Demographics of the patients are presented in Table 1. A comparison of venous thromboembolism rates. Pre-operative creatinine was higher in the enoxaparin group (0.81 ± 0.19 vs. 0.72 ± 0.18, p < 0.001). With the numbers available for study, there were no demonstrable differences in DVT (p = 0.400, power = 0.125), PE (p = 0.679, power = 0.066), cerebrovascular events (p = 0.913, power = 0.049), or transfusion rates (p = 0.412, power = 0.121). Conclusion:. To our knowledge this is one of, if not the largest non-industry funded studies comparing these two medications. There were no statistically demonstrable differences between the enoxaparin and rivaroxaban groups in terms of venous thromboembolism or major bleeding complications

Routine prophylaxis is recommended to prevent venous thromboembolism (VTE) – manifesting as deep vein thrombosis (DVT) and/or pulmonary embolism (PE) – in patients undergoing major orthopaedic surgery. Rivaroxaban (BAY 59-7939) is a novel, oral, direct Factor Xa inhibitor in development for the prevention and treatment of VTE. The efficacy and safety of 5–9 days’ prophylaxis with rivaroxaban were investigated in three randomized, double-blind, phase IIb trials in patients undergoing elective, total hip or knee replacement (THR or TKR), relative to subcutaneous enoxaparin. Two trials (one in patients undergoing THR, N=722; and one in patients undergoing TKR, N=621) investigated twice-daily (bid) rivaroxaban (at total daily doses of 5–60 mg); the third (in patients undergoing THR, N=873) investigated once-daily (od) rivaroxaban (at doses of 5, 10, 20, 30 or 40 mg od). Rivaroxaban – at all doses tested – had similar efficacy to enoxaparin in the bid trials. This promising finding was strengthened by the od trial, in which the observed incidences of the primary efficacy endpoint (DVT, non-fatal PE or all-cause mortality) were lower in patients receiving rivaroxaban 5, 10, 20, 30 and 40 mg od (14.9%, 10.6%, 8.5%, 13.5% and 6.4%, respectively) than enoxaparin (25.2%). Although there was no significant dose–response relationship between rivaroxaban and the primary efficacy endpoint in these trials, there was with major VTE (proximal DVT, PE or VTE-related death; p=0.0072) in the od trial (incidences were 8.5%, 2.7%, 0.9%, 1.9% and 1.1% with rivaroxaban 5, 10, 20, 30 and 40 mg od, respectively, vs 2.8% with enoxaparin). Significant dose–response relationships between rivaroxaban and major bleeding were observed in all three trials. In the bid trials, major bleeding rates with rivaroxaban were similar to those with enoxaparin at total daily doses of 5–20 mg. In the od trial, major bleeding occurred in 2.3%, 0.7%, 4.3%, 4.9% and 5.1% of patients receiving rivaroxaban 5, 10, 20, 30 and 40 mg od, respectively, and in 1.9% of those receiving enoxaparin. Rivaroxaban was generally well tolerated in the bid and od trials, and the incidence of nausea and vomiting with early post-operative oral rivaroxaban administration was low for all doses tested. The bid trials suggest that oral rivaroxaban at total daily doses of 5–20 mg may be a safe and effective alternative to enoxaparin for the prevention of VTE after major orthopaedic surgery. The od trial suggests that the more-convenient od regimen is feasible and that 10 mg od, a dose within the range identified by the bid trials, should be investigated further. As a result, oral rivaroxaban 10 mg od is currently being investigated in four phase III trials for the prevention of VTE after major orthopaedic surgery (the RECORD trials)

Aims. This phase II safety study aimed to investigate the bleeding side effect profile in patients treated with Rivaroxaban as a new agent for venous thromboembolism (VTE) prophylaxis following hip or knee arthroplasty. Methods. A retrospective study of complications was conducted in 88 consecutive patients undergoing hip and knee arthroplasty at one centre. Patients received chemical and/or mechanical VTE prophylaxis according to local guidelines. Data was collected from notes and evaluated using Fisher's exact test and t-Test. Significance was determined if p< =0.05. The primary end-point was local wound site oozing or bleeding. Secondary end-points were drop in haemoglobin, drain output and infection. Results. 55 patients were treated with Rivaroxaban, 18 with mechanical prophylaxis only, 10 with Enoxaparin and 5 with aspirin, clopidogrel or warfarin. The Rivaroxaban cohort demonstrated a statistically significant amount of increased major bleeding (24% vs. 0% p=0.03) and wound oozing (27% vs. 0% p=0.02) when compared to patients treated with Enoxaparin. Compared to those treated with other methods of VTE prophylaxis, Rivaroxaban also significantly increased major bleeding (24% vs. 6% p=0.01) and wound oozing (27% vs. 12% p=0.03). The Rivaroxaban cohort demonstrated a significantly larger drop in haemoglobin compared to the combined non-Rivaroxaban group (3.0 vs. 2.4 g/dL p=0.04). There was no significant difference in drain volume or rate of infection between groups. Conclusions. Rivaroxaban appears to cause increased wound site bleeding in comparison to Enoxaparin and other methods of thromboembolism prophylaxis. Further use of Rivaroxaban at this centre was therefore discontinued; however, the small group sizes and retrospective non-randomised design of this study introduce bias and limit the reliability of its findings. Prospective randomised controlled trial focused on wound complications is required to eliminate selection and reporter biases

Patients with hip fracture are at high risk of venous thromboembolism (VTE). Chemical thromboprophylaxis with low molecular weight heparin (LMWH) is associated with a risk of major bleeding in certain patient groups, such as those with renal failure. In these patients, unfractionated heparin should be used. Our aim was to determine the practice of VTE risk assessment in patients admitted with hip fracture against the national guidance, which states that all should have VTE risk assessment on admission. We also assessed the impact of introducing the VTE risk assessment form on prescribing practice of chemical thromboprophylaxis in patients with renal failure. Prospective audit of patients of 50 patients admitted with hip fracture from 4/8/10 with re-audit of 50 patients admitted from 17/2/2011 after introducing the VTE risk assessment form into the hip fracture admissions proforma. Retrospective analysis was undertaken to determine chemical thromboprophylaxis prescribing in patients with eGFR <30ml/min/1.73m. 2. . Patient demographics were comparable in both audit loops, with the mean age being equal (84 years) and an equal majority of female patients (76%). There were similar numbers of patients with eGFR <30ml/min/1.73m. 2. in both audit loops with 8% (n=4) in the initial audit, and 10% (n=5) in the re-audit. Frequency of VTE risk assessment significantly increased from 16% to 86% after including the VTE risk assessment form in the hip fracture proforma (p<0.0001). Despite this, there was no significant reduction in prescribing of LMWH in patients with renal failure with eGFR <30ml/min/1.73m. 2. , (P=0.52). Documentation of VTE risk assessment in patients admitted with hip fracture can be improved by simple measures such as inclusion of the VTE risk assessment form in the admissions proforma. However, this did not result in a reduction of LMWH prescribed in patients with significant renal failure and risk of major bleeding

Hypothesis. Pre-specified pooling of data from the four phase III RECORD studies was conducted to determine whether rivaroxaban significantly reduced the less-frequent clinical endpoint of symptomatic venous thromboembolism (VTE) and all-cause mortality after total hip or knee arthroplasty (THA or TKA, respectively), compared with standard North American and European enoxaparin regimens. Methods and analysis. Patients (n=12,729) received rivaroxaban 10 mg once daily or enoxaparin 40 mg once daily (RECORD1-3) or 30 mg 12-hourly (RECORD4). Thromboprophylaxis was administered for 31-39 days (RECORD1; THA) or 10-14 days (RECORD3 and 4; TKA). RECORD2 (THA) compared 31-39 days' rivaroxaban with 10-14 days' enoxaparin followed by placebo. The pre-specified primary efficacy endpoint in the pooled analysis (composite of symptomatic VTE and all-cause mortality) and adjudicated bleeding events were analysed in the day 12±2 active treatment pool, when all patients had received active drug, and total treatment duration pool, where subgroup analyses were performed. Results. In the day 12±2 active treatment pool, the primary efficacy endpoint occurred in 0.5% of patients receiving rivaroxaban versus 1.0% of patients receiving enoxaparin (p=0.001). Major bleeding occurred in 0.3% versus 0.2% patients respectively (p=0.18) and major plus clinically relevant non-major bleeding occurred in 2.9% versus 2.5% patients respectively (p=0.19). In the total treatment duration pool, rivaroxaban significantly reduced the primary efficacy endpoint compared with enoxaparin regimens 0.6% versus 1.3% patients (p< 0.001) with similar rates of major bleeding. Over the total treatment period, rivaroxaban consistently reduced the primary efficacy endpoint across the pre-specified subgroups (age, gender, body weight, creatinine clearance). Conclusion. Rivaroxaban significantly reduced the composite of clinically important symptomatic VTE and all-cause mortality after THA or TKA compared with subcutaneous enoxaparin regimens in the direct comparison day 12±2 active treatment pool, with no significant differences in bleeding events. These results suggest a positive benefit-risk profile for oral, once-daily rivaroxaban

Introduction. In Japan, edoxaban has been used for the prevention of venous thromboembolism (VTE) after total knee arthroplasty (TKA) since June 2011. Edoxaban is an oral direct factor Xa inhibitor, expected to be more convenient for the postoperative treatment of TKA. Enoxaparin, a II and Xa inhibitor, was approved in Japan for the prevention of VTE in patients undergoing orthopedics surgery from 2008. In this study, the effect for the prevention of VTE after TKA was compared between these two drugs in Japanese patients. Patients and Methods. We studied 42 Japanese patients who underwent TKA from May 2011 to April 2012. The operations were performed under general anesthesia, continuous femoral nerve block, an air tourniquet, and using cements for implant fixation. These patients were divided in two groups, use of 30 mg edoxaban once daily (ED group), and use of 1000 IU of enoxaparin twice daily (EN group). The initial dose was administered between 12 and 21 hours after surgery. We compared the incidence of VTE, bleeding complications, D dimer levels, and hemoglobin (Hb) loss. The screening of VTE was performed by enhanced CT scan screening from the chest to the foot on postoperative day 5 or 6 in all patients. The bleeding complication was divided into major bleeding and minor bleeding with Japanese guideline for the prevention of VTE. D dimer levels and Hb levels were preoperatively and postoperative day 1, 3, 5, 7, and 14. The loss of Hb was calculated from preoperative Hb level minus lowest postoperative Hb level. Results. The following results is showed in the order as ED group, EN group. The incidence of VTE was 45%, 32%, that was higher in ED group (see figure 1). There were almost no differences between both groups about D dimer levels and Hb loss in follow up period (see figure 2, 3). There were no major bleeding in both groups. The incidence of minor bleeding were 20%, 32%, that was higher in EN group (see figure 4). Discussion. We compared the effect of edoxaban and enoxaparin for the prevention of VTE. These two drugs are different way of administration. Edoxaban is administered orally, on the other enoxaparin requires with hypodermic injection. Therefore edoxaban is expected to be more convenient and less complaints than enoxaparin for the prevention of VTE. However our study showed that the use of 30 mg edoxaban once daily was less efficacy than the use of enoxaparin 1000 IU twice daily. The bleeding complication was lower incidence in the edoxaban, thus consideration should be given to the administration dosage of edoxaban to Japanese patients

Introduction: Rivaroxaban is a novel, oral, direct Factor Xa inhibitor in advanced clinical development for the prevention and treatment of thromboembolic disorders. In this phase III trial, the efficacy and safety of thromboprophylaxis with rivaroxaban was compared with enoxaparin in patients undergoing total knee replacement (TKR). Methods: In RECORD3 – a randomized, double-blind trial – patients received rivaroxaban 10 mg 6–8 hours after surgery and once daily (od) thereafter, or enoxaparin 40 mg od beginning the evening before surgery; both were continued for 10–14 days. The primary efficacy outcome was the composite of any deep vein thrombosis (DVT), non-fatal pulmonary embolism (PE) and all-cause mortality. Secondary efficacy outcomes included major venous thromboembolism (VTE; the composite of proximal DVT, PE and VTE -related death) and symptomatic VTE. The primary safety outcome was major bleeding, and other safety outcomes included any on-treatment bleeding and haemorrhagic wound complications (the composite of excessive wound haematoma and surgical-site bleeding). Results: A total of 2531 patients were randomized; 2459 were eligible for inclusion in the safety population and 1702 for the modified intention-to-treat population. The primary efficacy outcome was reported in 9.6% of patients receiving rivaroxaban and 18.9% of patients receiving enoxaparin. This equated to a relative risk reduction of 49% (p< 0.001) with rivaroxaban compared with enoxaparin. The incidence of major VTE was also significantly reduced with rivaroxaban compared with enoxaparin (relative risk reduction 62%, p=0.016). The incidence of symptomatic VTE was significantly lower in the rivaroxaban group than in the enoxaparin group (p=0.005). Major bleeding rates were 0.6% and 0.5% in the rivaroxaban and enoxaparin groups, respectively, and rates of any on-treatment bleeding were 4.9% and 4.8%, respectively. The incidence of haemorrhagic wound complications was 2.1% in the rivaroxaban group and 1.9% in the enoxaparin group. Conclusions: Rivaroxaban was significantly more effective than enoxaparin for the prevention of VTE after TKR, with a similar safety profile. The oral, direct Factor Xa inhibitor rivaroxaban, given as a fixed, unmonitored dose, may have the potential to change clinical practice for thromboprophylaxis after TKR

Purpose: Rivaroxaban is a novel, oral, direct Factor Xa inhibitor in advanced clinical development for the prevention and treatment of thromboembolic disorders. RECORD3 was a phase III trial conducted to compare the efficacy and safety of oral rivaroxaban with subcutaneous enoxaparin for the prevention of venous thromboembolism (VTE) in patients undergoing total knee replacement (TKR). Method: In this randomized, double-blind trial, patients received rivaroxaban 10 mg once daily (od), or enoxaparin 40 mg od. Enoxaparin was initiated the evening before surgery, and rivaroxaban 6–8 hours after surgery; therapy continued for 10–14 days. The primary efficacy outcome was the composite of any deep vein thrombosis (DVT), pulmonary embolism (PE), and all-cause mortality. Secondary efficacy outcomes included major VTE (the composite of proximal DVT, PE, and VTE-related death) and symptomatic VTE. Major bleeding was the primary safety outcome. Other safety outcomes included any on-treatment bleeding and hemorrhagic wound complications (the composite of excessive wound hematoma and surgical-site bleeding). Results: A total of 2531 patients were randomized; 2459 were eligible for inclusion in the safety population and 1702 for the modified intention-to-treat population. The incidence of the primary efficacy outcome was significantly reduced with rivaroxaban compared with enoxaparin (relative risk reduction 49%, p< 0.001). Major VTE occurred in 1.0% and 2.6% of patients receiving rivaroxaban and enoxaparin, respectively (relative risk reduction 62%, p=0.016). The incidence of symptomatic VTE was significantly lower in the rivaroxaban group than in the enoxaparin group (p=0.005). Major bleeding rates were 0.6% and 0.5% in the rivaroxaban and enoxaparin groups, respectively, and rates of any on-treatment bleeding were 4.9% and 4.8%, respectively. The incidence of hemorrhagic wound complications was 2.1% in the rivaroxaban group and 1.9% in the enoxaparin group. Conclusion: Rivaroxaban was significantly more effective than enoxaparin for thromboprophylaxis after TKR. Importantly, the incidence of bleeding was low and similar in both groups. This is the first trial to demonstrate the efficacy and safety of a fixed, unmonitored regimen of an oral, direct Factor Xa inhibitor – rivaroxaban – for thromboprophylaxis after TKR

The oral direct thrombin inhibitor dabigatran etexilate (Pradaxa. ®. ) was recently approved in Europe for the prevention of venous thromboembolism (VTE) in patients undergoing elective total knee or total hip replacement surgery. In the Phase III RE-MODEL (. Eriksson BI et al. . J Thromb Haemost. 2007. ; . 5. : . 2178. –2185. ) and RENOVATE (. Eriksson BI et al. . Lancet. 2007. ; . 370. : . 949. –956. ) clinical trials the safety and efficacy of 220 mg and 150 mg dabigatran etexilate once daily were studied. In both trials these doses were compared with 40 mg subcutaneous enoxaparin. A post hoc pooled analysis was performed in patients with moderate renal impairment (glomerular filtration rate ≥ 30 and < 50 ml/min) who participated in these two trials. The primary efficacy endpoint in both studies and the post hoc analysis was total VTE and all cause mortality; the key pre-specified secondary efficacy endpoint was major VTE and VTE-related mortality. Bleeding events (the primary safety endpoint) were blindly adjudicated and categorised as major bleeding events (MBE), which includes surgical site bleedings. A total of 1825 patients were treated with 220 mg dabigatran etexilate, 1866 with 150 mg dabigatran etexilate and 1848 with 40 mg enoxaparin. Of these, 337 patients had moderate renal impairment. 68% of these patients could be evaluated for the primary efficacy endpoint, 72% for the secondary efficacy endpoint, and all patients were included in the safety and bleeding analyses. The incidence of total VTE and all cause mortality was 17.7% (14/79), 23.5% (16/68) and 27.8% (25/90) in the 220 mg dabigatran etexilate, 150 mg dabigatran etexilate and enoxaparin groups, respectively. When the secondary efficacy endpoint was analysed a similar trend was seen, with a descriptive statistical significance for a lower event rate in the 220 mg group: 1.2% (1/83; p=0.04 vs enoxaparin using Fisher’s exact test), 4.3% (3/70) with 150 mg dabigatran etexilate; and 9.0% (8/89) in the enoxaparin group. MBE occurred in 6/113 patients (5.3%) in the 220 mg dabigatran etexilate-treated group, in none of the patients in the 150 mg dabigatran etexilate-treated group (0/96; p=0.04 vs enoxaparin using Fisher’s exact test), and in 6/128 patients (4.7%) receiving enoxaparin. Of note, 3/6 MBE in the 220 mg group started before oral dabigatran etexilate treatment was initiated. In conclusion, oral 150 mg dabigatran etexilate showed similar efficacy compared with subcutaneous enoxaparin in patients with moderate renal impairment undergoing hip or knee replacement surgery, with an apparently lower rate of major bleeding. As bleeding is a major concern, especially in this population, the 150 mg once daily dose of dabigatran etexilate is currently recommended by EMEA for this group

Continuous neuraxial or deep peripheral nerve blockade used to provide postoperative analgesia after major orthopaedic surgery is associated with a risk of spinal or perineural haematoma, especially in patients concomitantly receiving anticoagulants. Limited data on the use of fondaparinux in surgical patients in whom this procedure is performed are available. The EXPERT trial was an observational international study in patients undergoing major orthopaedic surgery designed to evaluate the overall efficacy and safety of once-daily 2.5 mg fondaparinux initiated 6 to 12 hours post-operatively and administered for 4±1 weeks after surgery. A 48-hour “therapeutic window” was applied in patients in whom a neuraxial/deep peripheral indwelling catheter was placed: one of the planned doses of fondaparinux was omitted, the catheter was removed 36 hours after the previous fondaparinux dose, and the next fondaparinux dose administered 12 hours after catheter removal. The primary endpoints were symptomatic venous thromboembolism (VTE) and major bleeding 5±1 weeks after surgery. These events were validated by an independent adjudication committee. Overall, 5704 patients (mean age ± SD: 66 ± 12 years) were recruited between July 2003 and October 2004. They underwent surgery for total hip replacement (52%, n=2941), knee replacement (40%, n=2263), hip fracture (6%, n=353), or other indications (3%, n=148). Fondaparinux was given for a median of 35 (range: 1–105) days. Many operations (62%) were performed under regional anaesthesia only. A neuraxial or deep peripheral nerve block catheter was placed in 29% (n=1630) of patients. It was removed between one and two days after surgery in 43% (706/1626), and between three and six days after surgery in 57% (920/1626). Overall, the rate of symptomatic VTE was 1.0% (54/5387); it was 0.8% (13/1535) in patients with catheter and 1.1% (41/3852) in patients without catheter, giving an odds ratio of 0.79 (95% CI: 0.42 to 1.49) in favour of patients with a catheter. The upper limit of the 95% CI being below the predetermined non-inferiority margin of 1.75, the efficacy of fondaparinux in patients with a catheter was therefore not inferior to that observed in patients without a catheter. The rate of major bleeding was 0.8% (42/5382) overall, 0.5% (7/1532) in patients with catheter and 0.9% (35/3850) in patients without catheter. No spinal or perineural hematomas or nerve damage were reported. At 5±1 weeks, 23 (0.4%) patients had died. In conclusion, 2.5 mg fondaparinux given daily for 4±1 weeks after major orthopaedic surgery was both effective and safe in routine practice. This benefit-risk ratio was similar in 1630 patients with a neuraxial/ deep peripheral indwelling catheter in whom a 48-hour “therapeutic window” was applied

Little is known about the efficacy of graduated compression stockings in preventing venous thromboembolism after hip surgery. We conducted a prospective, randomised single-blind study to determine whether the addition of compression stockings to fondaparinux conferred any additional benefit. The study included 874 patients, of whom 795 could be evaluated (400 in the fondaparinux group and 395 in the fondaparinux plus compression stocking group). Fondaparinux was given post-operatively for five to nine days, either alone or combined with wearing stockings, which were worn for a mean 42 days (35 to 49). The study outcomes were venous thromboembolism, or sudden death before day 42. Duplex ultrasonography was scheduled within a week of day 42. Safety outcomes were bleeding and death from venous thromboembolism. The prevalence of deep-vein thrombosis was similar in the two groups 5.5% (22 of 400) in the fondaparinux group and 4.8 (19 of 395) in the fondaparinux plus stocking group (odds ratio 0.88, 95% confidence interval 0.46 to 1.65, p = 0.69). Major bleeding occurred in only one patient. The addition of graduated compression stockings to fondaparinux appears to offer no additional benefit over the use of fondaparinux alone

Thromboembolic disease (TED) remains as a major concern for orthopaedic surgeons and is a well-known complication of lower extremity joint replacement procedures. While there is voluminous literature on the topic, it is difficult for the average orthopaedic surgeon to keep up with all the advancements in this area as well as the newer pharmacological options for prophylaxis. To address this, the American Academy of Orthopaedic Surgeons (AAOS) has developed a clinical practice guideline (CPG) in this area to provide treatment recommendations based on the best available evidence. Historically, guidelines for TED prophylaxis have been based largely on randomised controlled trials whose outcome measure was venographically documented deep vein thrombosis (DVT). However, many venographically documented DVTs, particularly those distal to the popliteal vein, are of no clinical consequence. Therefore, in the AAOS CPG the systematic review of the literature was focused on those outcomes that have the most clinical relevance: all-cause mortality, symptomatic or fatal pulmonary embolism (PE), proximal DVT, major bleeding and symptomatic DVT rates. Using these as the clinically important endpoints, it is evident that the extant literature is insufficient to provide definitive guidance in this area and to make specific recommendations about optimal pharmacological prophylaxis. Nonetheless, one strong recommendation has emerged from this systematic review: the guideline recommended against routine post-operative duplex ultrasonography screening of patients who undergo elective hip or knee arthroplasty. Only one risk factor – previous history of TED – had evidence demonstrating a higher risk beyond the risk from elective hip or knee arthroplasty itself (weak recommendation). There was not sufficient evidence that other potential risk factors increase the risk of TED, likely because of the relatively high background risk of elective hip or knee arthroplasty. In addition, there is very little evidence defining populations at increased risk for bleeding and bleeding-associated complications associated with pharmacological prophylaxis. However, the panel did come to a consensus that patients with known bleeding disorders or active liver disease are at an increased risk for post-operative bleeding. In these circumstances, it is recommended that mechanical compressive devices be the primary modality of prophylaxis as pharmacologic prophylaxis may increase the risk of bleeding. There was a moderate strength recommendation for the superiority of neuraxial anesthesia to limit blood loss even though there is no demonstrable effect on the incidence of TED. Finally, there was a moderate grade recommendation that pharmacologic agents (including aspirin) and/or mechanical compression devices be utilised for the prevention of VTE in patients that are undergoing elective hip or knee arthroplasty who are not at elevated risk beyond that of the surgery itself for VTE or bleeding. Clearly there is great need for better evidence with appropriately powered studies that examine the most clinically relevant outcomes in TED prophylaxis

Background. Venous thromboembolism (VTE) is a common, costly, and morbid complication following TJA. Consequently, the current standard of care recommends that all TJA candidates receive some form of thromboprophylaxis postoperatively. Chemoprophylaxis, however, is not without its own risks and has been associated with greater risk of perioperative complications such as major bleeding, infection, stroke, and increased wound drainage. Mechanical compression devices serve as an alternative to chemoprophylaxis. Compression devices are thought to function by decreasing venous stasis and activating fibrinolysis. Intermittent pneumatic compression devices (IPCD) function by providing pressure at a constant cycle; whereas continuous enhanced circulation therapy (CECT) devices such as ActiveCare portable system (Medical Compression Systems, Or Akiva, Israel) function in a synchronized manner with the patient's own respiratory cycles. While both of these systems are widely utilized, there is scarce data comparing their effectiveness as thromboprophylatic agents following TJA. The purpose of this meta-analysis is to comparatively evaluate the efficacy of ActiveCare to IPCDs in the prevention of thromboembolic events following TJA. Methods. A literature search using PubMed, Cochrane, and EMBASE databases were used to identify all articles published between January 2000 and August 2016. Key words used to conduct the search were venous foot pump, intermittent pneumatic compression, total hip arthroplasty/replacement, total knee arthroplasty/replacement, deep vein thrombosis, thromboembolic disease and pulmonary emboli. Two independent investigators carried out the literature review using the PRISMA guidelines (Figure 1). Analysis of risk ratio was performed by evaluation of studies which compared IPCD with any control chemoprophylaxis regiment or ActiveCare with any control chemoprophlaxis regiment. Assessment of heterogeneity and analysis of data were operated by Review Manager 5.3. Results. Our primary search protocol yielded 968 individual studies by both reviewers of which 525 were duplicates. After screening the remaining 443 abstracts for relevancy 357 were excluded, leaving 86 for full text examination. After a thorough evaluation, 60 were further excluded, and a total of 24 studies, published between 2000 and 2014, were included for analysis, representing 9,134 patients. Of these, 13 were randomized controlled trials and 11 were retrospective studies. When compared to control chemoprophylactic groups, the risk ratio (RR) of DVT development was 0.51 (95% CI: 0.39 – 0.67; I. 2. =69%) with NSIPCDs and 0.47 (95% CI: 0.27 – 0.80; I. 2. =0%) with RSCDs. The RR for development of PE in these groups respectively were 0.24 (95% CI: 0.04 – 0.15) versus 0.55 (95% CI: 0.35 – 0.88) (Figure 3). Conclusion. When compared to chemoprophylaxis alone, compression devices appear to reduce the incidence of VTEs following TJA. The addition of mechanical prophylaxis to any chemoprophylactic regimen increased VTED prevention Following a comparative analysis of IPCDs and ActiveCare our study suggests that ActiveCare may be more effective at preventing VTE events, albeit not statistically significant. Thus, our results demonstrate that while both devices are effective thromboprophylactic modalities, more research is warranted to better elucidate the strengths and limitations of compression devices as thromboprophylatic agents. For any figures or tables, please contact the authors directly

Background. This retrospective analysis was prompted by the authors' observation of the relatively high incidence of venous thromboembolism (VTE) in the surgical repair of acute Achilles tendon ruptures. Method. 88 patients were treated surgically for an acute Achilles tendon rupture. No prophylactic anticoagulation was given to any patients. The incidence of VTE was then reviewed retrospectively. Results. Five patients developed symptomatic deep vein thrombosis (5.7%) and one a near-fatal pulmonary embolus (1.1%). There were no major bleeding or cardiovascular adverse events. One patient developed a thrombus of the the lesser saphenous vein (1.1%) and there was one superficial sepsis (1.1%). A temporary peroneal nerve palsy occurred in one patient (1.1%). There were two re-ruptures (2.3%). Conclusion. There is no doubt that thromboprophylaxis must be given to the high risk patient and is also recommended for major orthopaedic surgery. Limited data is available for the use of thromboprophylaxis in foot and ankle surgery. In light of the unacceptably high incidence of venous thromboembolism in this study, the authors suggest that routine venous thromboembolism prophylaxis should be considered for these patients. MULTIPLE DISCLOSURES

The December 2023 Hip & Pelvis Roundup³⁶⁰ looks at: Early hip fracture surgery is safe for patients on direct oral anticoagulants; Time to return to work by occupational class after total hip or knee arthroplasty; Is there a consensus on air travel following hip and knee arthroplasty?; Predicting whether patients will achieve minimal clinically important differences following hip or knee arthroplasty; High-dose dual-antibiotic-loaded cement for hip hemiarthroplasty in the UK (WHiTE 8): a randomized controlled trial; Vitamin E – a positive thing in your poly?; Hydroxapatite-coated femoral stems: is there a difference in fixation?

Rivaroxaban is an oral anticoagulant which has the potential to replace subcutaneous Clexane in post operative prophylaxis of venous thromboembolism following knee replacement. Rivaroxaban has been shown to be at least equivalent to Enoxaparin in the prevention of deep venous thrombosis and pulmonary embolism with a similar rate of major bleeding. However, the morbidity associated with the new product has yet to be fully examined. Our own anecdotal evidence suggests that Rivaroxaban may be associated with poorer knee range of motion, and greater bruising and haemarthrosis. This pilot study aimed to compare these outcomes as well as knee pain and length of hospital stay in patients receiving Rivaroxaban and Enoxaparin following total knee replacement. A controlled before and after study with single blinding was performed. Patients in the ‘Before’ group were given Rivaroxaban (our current protocol). Patients treated in the “After’ group were subjected to our previous protocol (Enoxaparin). Patients were followed up to 6-weeks post surgery. Blinded assessors reviewed range of motion and wound outcomes using a photographic method. Swelling was measured using a standardized technique. Bleeding, pain and length of stay were prospectively recorded. Data analysis is due to be completed in April 2011. Complete results will be available after this time. Discussion: Rivaroxaban was introduced to lessen patient burden as oral administration is presumed to be more acceptable than self-injection of Enoxaparin. It is yet to be determined comprehensively whether the benefits of oral administration outweigh any associated risks. Surgeons must carefully consider the risks and benefits of their choice of venous thrombosis prophylaxis following total knee replacement

The risk of venous thrombo-embolism (VTE) is high in orthopedics. Oral direct factor Xa inhibitors have been introduced to help reduce the incidence of VTE. To reduce post-operative bleeding antifibrinolytics are used. We aimed to ascertain the effect of two drugs on post operative bleeding and transfusion requirements. We prospectively recorded patient demographics, operative details, complications, transfusion incidence and VTE incidence in TKR patients. We also sent out questionnaires to patients asking about wound bleeding and VTE. All patients were given 10mg Rivaroxaban 8 hours post operatively and then OD for 14 or 35 days. Patients given tranexamic acid were given 500mg IV, 5 minutes prior to wound closure at the discretion of the surgeon. VTE was Deep Vein Thrombus or Pulmonary Embolism confirmed by Doppler or CTPA. Minor bleed was categorized as dressing soakage or reported wound leakage, major bleed as hematoma requiring revision within 30 days. 509 patients underwent TKR: 200 (39%) received Rivaroxaban only (Group 1), 296 (58%) also received tranexamic acid (Group 2). 13 (3%) patients had no data available. Five patients had a VTE: 4 (2%) in Group 1, 1 (0.3%) in Group 2 [P<0.05]. 39 patients had a minor bleed: 17 (8.5%) in Group 1, 22 (7.4%) in Group 2 [P=0.5]. 2 patients had major bleeds: 1(0.5%) in Group 1 and 1(0.33%) in Group 2 [P=0.69]. There were 30 blood transfusions: 21 (10.5%) in Group 1, 9 (3%) in Group 2 [P<0.0001]. We have demonstrated a reduced requirement for blood transfusions in the tranexamic acid group. However our results, whilst they show a trend towards decreased minor and major bleeding rates, are not significant and require larger studies looking at wound bleeding and leakage

Introduction. Rivaroxiban is a direct inhibitor of factor Xa, a licensed oral thromboprophylactic agent that is increasingly being adopted for lower limb arthroplasty. Rivaroxiban has been NICE-approved for use in primary hip and knee arthroplasty following the RECORD 4 trials; proving it more effective in preventing venous thrombo-embolic (VTE) events compared to enoxaparin. Enhanced Recovery Programmes (ERP) are designed to enable patients to recover quickly and return home safely within a few days. Methods. We prospectively studied 1223 patients (age- and sex-matched) who underwent lower-limb arthroplasty enrolled in our ERP between March 2010 and December 2011; 454 patients (Group 1) received enoxaparin, 769 patients (Group 2) received rivaroxiban. Patients wore thrombo-embolic stockings for six weeks post surgery. Patients were monitored for thrombo-embolic events and wound-related complications for 42 days post-operatively. Results. 1223 patients underwent lower-limb arthroplasty during our study period. There were similar numbers of THRs and TKRs in each group 230:224 and 370:399. Average length of stay was 4.9 days (range 1–19) in group 1 and 4.5 days (range 2–23) in group 2. The rate of VTE events was the same in both groups (< 1%). In group 1 (enoxaparin), 21(4.6%) of the 454 patients experienced oozing/infected wounds that required further surgical attention. In group 2 (rivaroxiban), 46 (6%) of the 769 patients had wound-related complications, of which 70% were in primary THR patients. Conclusion. Rivaroxabans use in clinical practice has been questioned concerning its wound-related complications. The RECORD 4 trial focused on major bleeding as the primary safety outcome, however we postulate slow post-operative oozing can lead to haematoma formation, increasing the risk of superficial wound and deep infections potentially requiring revision surgery. This study shows an increased wound complication rate in the Rivaroxiban group, highlighting the need for further clinical trials to assess its safety and efficacy

Introduction. Oral factor Xa inhibitors have recently been licensed for use as thromboprophylaxis in arthroplasty surgery. Phase IV trials have proven there efficacy in DVT/PE prevention with comparable rates in major adverse events, including major bleeding. We examined whether the introduction of rivaroxoban, an oral factor Xa inhibitor, increased total blood loss in patients undergoing primary arthroplasty surgery. Methods. Two groups were studied. The intervention group were prescribed rivaroxoban thrombophrophylaxis 6–10 hours post-surgery, and the control group were prescribed low molecular weight heparin (daltaparin 5,000u) 6–10 hours post-surgery. All other factors were kept constant. Pre- and post-operative haemoglobin levels (post-operative day 2) were recorded. Any requirement for transfusion was also documented. Actual drop in haemoglobin levels was compared between the two groups. Results. 91 patients were prescribed rivaroxoban (48 THR and 43 TKR), and 71 were included in the control group (34 THR and 37 TKR). Baseline pre-operative haemoglobin were comparable (p=0.43; 13.0 vs 13.2g/dL), however, post-operative blood loss was significantly increased in the rivaroxoban group (p=< 0.0001; 3.6 vs 2.8g/dL). Total knee replacements had a significant increase in post-operative blood loss in the rivaroxoban group (p=< 0.0001; 3.4 vs 2.6g/dL). Total hip replacement surgery had an increase in total blood loss in the rivaroxoban group, but this did not reach statistical significance (p=0.33; 3.8 vs 3.3g/dL). More patients undergoing TKR required transfusion in the rivaroxoban group (0.07% vs 0.03%). Conclusions. Oral factor Xa inhibitors significantly increase post-operative blood loss in total knee arthroplasty surgery when compared with LMWH. There is a subsequent increased requirement for blood transfusion and the potential complications related to bleeding and transfusion. These factors must be considered and balanced with the ease of oral anticoagulation when introducing these newer agents in arthroplasty patients

Background: Prophylaxis against thromboembolic complications has become routine after major trauma and major orthopaedic surgery. In contrast, it remains an issue for debate whether prophylaxis after minor surgery and immobilization is necessary, even though these treatments are well-known risk factors for deep vein thrombosis (DVT). Objectives: The objective of this study was to evaluate the efficacy of Dalteparin (5,000 U given subcutaneously once daily for six weeks) during lower limb immobilization after surgical treatment of Achilles tendon rupture. Methods: After surgery, 105 consecutive patients were randomized to a placebo-controlled double-blind study to evaluate the efficacy of given thromboprophylaxis. DVT screening using validated color duplex sonography was performed three weeks and six weeks after surgery, and all DVTs were confirmed with phlebography. Results: Primary endpoint analysis was available for 91 patients. DVT was diagnosed in 16/47 patients (34%) in the Dalteparin group and in 16/44 patients (36%) in the placebo group. These figures are not significantly different (p=0.8). Proximal DVT was diagnosed in one patient (2%) in the Dalteparin group and in three patients (6%) in the placebo group (p=0.6). No pulmonary emboli or major bleeding occurred in either of the groups. Conclusions: DVT is common after surgical treatment of Achilles tendon rupture and therefore effective thromboprophylaxis is desirable. Thromboprophylaxis with Dalteparin however, does not affect the incidence of DVT during the immobilization after Achilles tendon rupture surgery. Long-term effects of immobilization, such as the risk for post-thrombotic syndrome, need to be investigated further

On the basis of observations made in recent years, it can be inferred that the incidence of venous thromboembolism (VTE) in Japan is as high as that in Western countries. Since 2007, the use of fondaparinux for the prophylaxis of VTE following lower-limb orthopedic surgery has been approved for Japanese patients. This study was performed with an aim to investigate the safety and efficacy of fondaparinux for the prevention of VTE following hip surgery in Japanese patients. From June 2007 to August 2008, we evaluated 141 consecutive patients (148 hips; average age, 65.6) undergoing total hip replacement (THR), consisted of cementless minimally invasive surgery, and hip fracture surgery (HFS), consisted of open reduction and internal fixation or bipolar hemiarthroplasty. We mainly used 2.5 mg of fondaparinux for a period extending up to 14 days. We estimated the symptomatic VTE and asymptomatic deep-vein thrombosis (DVT) rates in patients by ultrasonography performed on preoperative and postoperative day 3. In addition, we evaluated the pre-operative and postoperative plasma D-dimer levels on days 3, 7, and 14. We determined that both the preoperative and postoperative incidence of symptomatic VTE was 0%. A D-dimer value of 20 ug/ml or higher was not observed on preoperative days 3 and 7; however, this value was observed in 2 hips on postoperative day 14. The incidence of asymptomatic DVT was observed to be 0.8% preoperatively and 4% postoperatively. In particular, the corresponding value following HFS was observed to be 7.7% preoperatively. The incidence of the hemorrhagic event was observed to be 14.9%. Bleeding was mostly observed in the surgical and drainage areas. An overall major bleeding incidence of 0.7% (1 patient) was observed. The corresponding value in patients in whom the administration of fondaparinux was discontinued by day 14 was 18.9%. The study results indicate that fondaparinux is useful in Japanese patients for the prevention of VTE following hip surgery. However, the administration of this drug should be accompanied by additional measures to prevent the associated side effect of bleeding

Rivaroxaban is a novel, oral, once-daily, direct Factor Xa inhibitor in advanced clinical development. RECORD1 was a multinational, randomized, double-blind, double-dummy, phase III study investigating the efficacy and safety of extended thromboprophylaxis with rivaroxaban compared with subcutaneous enoxaparin following THR. Patients (N=4541) were randomized to receive oral rivaroxaban 10 mg (6–8 hours after surgery and once daily thereafter) or subcutaneous enoxaparin 40 mg (administered the evening before surgery, 6–8 hours after surgery, and once daily thereafter) for 35±4 days. The primary efficacy outcome was the composite of deep vein thrombosis (DVT: symptomatic or detected by mandatory, bilateral venography if asymptomatic), non-fatal pulmonary embolism (PE), and all-cause mortality up to day 36±6. Major venous thromboembolism (VTE), the composite of any DVT, non-fatal PE and VTE-related death, was a secondary outcome. Safety endpoints included major and non-major bleeding while receiving study medication. Rivaroxaban significantly reduced the incidence of the primary efficacy outcome compared with enoxaparin (1.1% vs 3.7%, respectively; p< 0.001; relative risk reduction [RRR] 70%). Rivaroxaban also significantly reduced the incidence of major VTE compared with enoxaparin (0.2% vs 2.0%, respectively; p< 0.001; RRR 88%). There were no significant differences in the incidence of major bleeding (0.3% vs 0.1%; p=0.178) or non-major bleeding (5.8% vs 5.8%; p=1.000) between rivaroxaban and enoxaparin, respectively. There was no evidence of liver safety issues associated with rivaroxaban. Thromboprophylaxis with once-daily, oral rivaroxaban was significantly more effective than subcutaneous enoxaparin following THR without an increased risk of bleeding. This trial demonstrates the efficacy and safety of a fixed, unmonitored, once-daily dose of oral rivaroxaban for extended thromboprophylaxis after THR

The purpose of this study was to determine the benefit and risk of NSAID-based prophylaxis for ectopic bone formation amongst patients undergoing total hip replacement (or revision) surgery. A double-blind randomised placebo-controlled clinical trial, stratified by treatment site and surgery (primary or revision), was conducted in 20 orthopaedic surgery centres in Australia and New Zealand. 902 patients, undergoing elective primary or revision total hip replacement surgery, were randomly allocated to 14 days treatment with ibuprofen (1200mg daily) or matching placebo commenced within 24 hours of surgery. Patients were only excluded if there was, in the opinion of the responsible physician, a definite indication or contra-indication for treatment with an NSAID during the 14 day study treatment period. Outcomes were assessed six to 12 months after surgery and included changes in self-reported hip pain and physical function (WOMAC), physical performance measures and radiographic evidence of ectopic bone formation. There was only a 6% loss to follow-up for self-report measures and a 12% loss to follow-up for radiographs. Six to twelve months after surgery, there were no significant differences between the ibuprofen and placebo groups for improvements in hip pain (mean difference, 95% confidence interval: −0.1, −0.4 to 0.2, p=0.6) or physical function (−0.1, −0.4 to 0.2, p=0.5), despite a much reduced risk of ectopic bone formation (relative risk 0.69, 95% confidence interval 0.56 to 0.83) associated with ibuprofen. There was a significantly increased risk of major bleeding complications during the admission period (2.09, 1.00 to 4.39). These data, from the largest-ever trial of prophylaxis against ectopic bone formation, do not support the use of routine NSAIDs-based prophylaxis for patients undergoing total hip replacement surgery

Current orthopedic practice requires consideration of apparently contradictory recommendations regarding VTE prevention among THR/TKR patients. American College of Chest Physicians (ACCP) 8th Clinical Practice Guidelines for the Prevention of Venous Thromboembolism recommend against aspirin for VTE prophylaxis in any patient. 1. The American Academy of Orthopedic Surgeons (AAOS) Guideline recommends pulmonary embolism risk stratification, then implementation of one of many possible courses including the use of aspirin. 2. . We conducted a prospective observational study among consecutive patients presenting for total hip or knee arthroplasty. Pre-operative PE risk stratification was performed at the discretion of the surgeon. Patients identified as usual risk for PE received aspirin. Patients considered being at elevated risk for PE received warfarin. This observational study protocol called for one year of data collection. At approximately 8 months 656 patients were enrolled, and the surgeon principally implementing PE risk stratification and administration of aspirin chose to stop enrolling patients due to a high incidence of pulmonary emboli. One hundred fifty five patients received thromboprophylaxis with aspirin 600 mg PR in the PACU, then 325 mg BID for one month (reduced to 81 mg daily if GI symptoms were present). The remaining 501 patients received an ACCP-based warfarin protocol managed by a pharmacist anticoagulation management service. Our hypothesis is the null hypothesis; that an AAOS-based approach to hromboembolism prevention is not inferior to an ACCP-based approach. The a priori primary endpoints of the AVP Study are clinically overt VTE, DVT, PE, major bleeding, and death. All patients will receive a 90 day follow-up questionnaire in person or by telephone. Additionally, the electronic medical record of Intermountain Healthcare will be interrogated for ICD-9 codes germane to the outcomes of interest. Ninety day follow-up has been completed for approximately 140 patients. The dataset will be locked upon completion of the 90 day follow-up among those patients who last received PE risk stratification and aspirin therapy (data lock early June, 2009). We anticipate preliminary data available for report by July, 2009

Introduction: After total hip replacement (THR), thromboprophylaxis for at least 10 days and for up to 35 days is recommended – yet a convenient, oral anticoagulant is not currently available. Rivaroxaban – a once-daily, oral, direct Factor Xa inhibitor with a predictable clinical profile – is in advanced clinical development. RECORD1, a multinational, randomized, double-blind, double-dummy, phase III study, compared once-daily oral rivaroxaban with subcutaneous enoxaparin for 5 weeks following THR. Methods: In total, 4541 patients were randomized to receive oral rivaroxaban 10 mg (6–8 hours after surgery and once daily thereafter), or 40 mg enoxaparin (administered subcutaneously the evening before surgery, resumed 6–8 hours after surgery, and continued once daily). Thromboprophylaxis was administered for 35±4 days; mandatory, bilateral venography was conducted the next day. The primary efficacy endpoint was the composite of any deep vein thrombosis (DVT), nonfatal pulmonary embolism (PE), and all-cause mortality. Safety endpoints included major and non-major bleeding during the active treatment period. Results: The incidence of the composite of DVT, PE, and all-cause mortality was significantly lower for rivaroxaban compared with enoxaparin (1.1% vs 3.7%, respectively; p< 0.001; relative risk reduction [RRR] 70%). The incidence of major VTE was also significantly lower for rivaroxaban compared with enoxaparin (0.2% vs 2.0%, respectively; p< 0.001; RRR 88%). There were no significant differences in the incidence of major bleeding (0.3% vs 0.1%; p=0.178) or non-major bleeding (5.8% vs 5.8%; p=1.000) between rivaroxaban and enoxaparin, respectively. There was no evidence of cardiac or liver safety issues. Conclusions: Following THR, thromboprophylaxis with once-daily, oral rivaroxaban was shown to be significantly more effective than subcutaneous, once-daily enoxaparin – without an increased risk of bleeding. This trial demonstrates the efficacy and safety of oral rivaroxaban using a fixed, unmonitored, once-daily dose for extended thromboprophylaxis after THR

Aims: We conducted an cost-utility analysis to compare standard (in-hospital) with prolonged (out-of-hospital) enoxaparin prophylaxis after elective total hip and knee replacement. Methods: The perspective was that of a societal healthcare payer, taking Belgium as a case country. The main outcome measure was the incremental cost-utility ratio, reported as the incremental cost per quality-adjusted life year gained (Euro/QALY). Costs for diagnosis and treatment of proximal and distal deep vein thrombosis, pulmonary embolism, postphlebitic syndrome, and major bleeding were obtained from a Delphi panel (orthopaedic surgeons) and the official reimbursement rates (Federal Ministery of Health). QALYs for these health states were based on utility scores as reported in the literature. Results: In the base-case analysis, incremental costs of prolonged prophylaxis amounted 58 Euro and 114 Euro per patient, with an additional gain in QALY of 0.0083 and 0.0018 after total hip and knee replacement, respectively. Thus, a strategy of prolonged enoxaparin prophylaxis was associated with a cost-utility ratio of 6,964 Euro/QALY and 64,907 Euro/QALY after total hip and knee replacement, respectively. Applying a societal willingness-to-pay threshold value of 20,000 Euro/QALY, prolonged enoxaparin prophylaxis is cost-effective after elective total hip replacement. Sensitivity analyses confirmed the general robustness of these findings. Conclusions: After elective total hip or knee replacement, prolonged enoxaparin prophylaxis leads to increased effectiveness at increased cost. Nevertheless, given the additional costs healthcare decision makers in Europe are usually prepared to pay for a gain in effectiveness, prolonged prophylaxis with enoxaparin is cost-effective after total hip replacement

Purpose: A retrospective database analysis was conducted to. determine the extent to which the American College of Chest Physicians (ACCP) guidelines for VTE prophylaxis are followed after total hip replacement (THR) and total knee replacement (TKR) and. evaluate the incidence of VTE for patients receiving and not receiving prophylaxis according to ACCP guidelines (‘ACCP’ and ‘non-ACCP’, respectively). Method: A claims database associated with a large US health plan was linked to the Premier database, which provides details of in-patient medication use. Patients ≥18 years undergoing TKR/THR and enrolled in the health plan 90 days before and 90 days following discharge from hospitalization (or until death) were included. Patients were considered to have received ACCP-guideline prophylaxis if they:. received LMWH, fondaparinux, or VKA following surgery. initiated prophylaxis within one day of surgery (for THR patients) and. were prescribed prophylaxis for a minimum of ten days, or until the occurrence of major bleeding, VTE, or death. In addition, the number of DVTs and PEs occurring in ACCP and non-ACCP patients was recorded. Results: Of the 30,644 eligible patients from the health plan, 3,497 patients were linked to the in-patient database. Except for geographic indicators, there were no significant differences in demographics or baseline co-morbidities between those included and excluded from the final study sample. Of the 3,497 linked patients, 1,395 (40%) received ACCP prophylaxis. The number of DVTs occurring in the ACCP and non-ACCP groups were 28 (2.01%) and 79 (3.76%), suggesting that non-ACCP patients were almost twice as likely as ACCP patients to have a DVT (p=0.0521). The number of PEs occurring in the ACCP and non-ACCP groups were 2 (0.14%) and 25 (1.19%), respectively, suggesting that non-ACCP patients were 8.5 times more likely than ACCP patients to experience a PE (p< 0.0001). Conclusion: This study offers a unique perspective on ‘real-world’ prophylaxis patterns and clinical outcomes in THR/TKR patients. It suggests that 40% of patients received ACCP prophylaxis and that patients not receiving ACCP prophylaxis were almost twice as likely to have a DVT and more than eight times as likely to experience a PE

Introduction: Venous thromboembolism (VTE) after major orthopaedic surgery remains an important clinical problem. Convenient, oral antithrombotic agents that are both safe and effective could improve adherence to guidelines for VTE prevention. Recently, the focus has been on the development of oral agents that target a single step in the coagulation cascade. Factor Xa is the pivotal point in the coagulation cascade, making it a particularly attractive target for anticoagulant drugs. Rivaroxaban is an oral, direct Factor Xa inhibitor. Four international phase III trials (the RECORD programme) are being undertaken to investigate the safety and efficacy of once-daily rivaroxaban for thromboprophylaxis after major orthopaedic surgery. The results of RECORD3 showed that rivaroxaban was more effective than enoxaparin 40 mg once daily after total knee replacement (TKR), with a 48% risk reduction in VTE and all cause mortality. RECORD4 is designed to compare rivaroxaban 10mg once daily with enoxaparin 30 mg every 12 hours for thromboprophylaxis following TKR. Methods: RECORD4 is a prospective, double-blind trial in which approximately 3000 TKR patients worldwide are being studied. Patients are randomized to receive either oral rivaroxaban 10 mg (starting 6–8 hours after surgery and continued once daily), or subcutaneous enoxaparin 30 mg (given every 12 hours and starting 12–24 hours after surgery). Study medication is given for 10–14 days, and mandatory bilateral venography is undertaken the following day. The primary efficacy outcome is a composite of deep vein thrombosis (DVT; symptomatic, or detected by mandatory venography), non-fatal pulmonary embolism (PE), and all-cause mortality. The major secondary efficacy outcome is major VTE (the composite of proximal DVT, PE and VTE-related death). The primary safety outcome is major bleeding. Other safety endpoints include all bleeding events, cardiovascular events and abnormal laboratory parameters. Results: The final results of this trial will be presented. Conclusions: The results of this trial will provide valuable data concerning the use of rivaroxaban for thromboprophylaxis after TKR in the North American setting

Introduction: Pharmacological and mechanical methods are recommended to prevent venous thromboembolism (VTE) following hip replacement (THR). However, data on mechanical methods such as graduated compressive stockings (GCS) are limited. This study examined the efficacy and safety of GCS when added to fondaparinux. Methods: The randomised treatments were 2.5 mg fondaparinux for 5–9 days starting postoperatively alone or with GCS for 42±7 days. The primary efficacy outcome was VTE or sudden death prior to Day 42±7. All patients were to have duplex USS at day 42 + 7. VTE was defined by verified symptomatic VTE or asymptomatic proximal DVT. The main safety outcomes were major and minor bleeding and VTE death. Results: 856 patients were randomised, of which 799 were THR patients. Of these 756 (95%) were evaluable, 377 in the fondaparinux and 379 in the fondaparinux plus GCS groups. Risk factors for thrombosis were recorded (age > 75 in 20%, history of obesity in 21%, cancer in 6% and VTE in 3%). Compliance with GCS was high, with 85% wearing them continuously. The primary efficacy outcome of VTE or sudden death in THR patients was similar in each treatment group, the results were 5.5% in the fondaparinux only group and 5.3% in the fondaparinux with GCS group; odds ratio was 0.96, 95% confidence interval 0.50–1.83, p=0.91. Outcomes were not different for long-length and short-length stockings. Major bleeding occurred in one patient (< 1%), minor bleeding in 6.7%. No VTE deaths were reported. Discussion: The addition of GCS to fondaparinux showed no benefit in thromboprophylaxis over fondaparinux alone in this large study of THR patients. Therefore GCS may not be indicated in patients receiving fondaparinux. Graduated compression stockings are time consuming to measure and fit, inconvenient and expensive; therefore we recommend a reconsideration of this current and commonly used practice in THR

Introduction: Venous thromboembolism (VTE) is a common, potentially fatal complication of major orthopaedic surgery. Although pharmacological thromboprophylaxis is recommended following total hip replacement (THR) for a minimum of 10 days, and up to 35 days, its extended use is not universally accepted – an effective, safe and convenient, oral anticoagulant would improve implementation of these recommendations. This trial compared short-term thromboprophylaxis using enoxaparin with extended thromboprophylaxis using rivaroxaban – a once-daily, oral, direct Factor Xa inhibitor – after THR, in the largest, prospective, randomized clinical trial conducted to date for the evaluation of the risk/benefit of extended prophylaxis. Method: In this global, double-blind trial, 2509 patients undergoing THR were randomized to receive either subcutaneous enoxaparin 40 mg once daily (od), started the evening before surgery and continued for 10–14 days, followed by placebo until day 35±4 (short-term prophylaxis), or oral rivaroxaban 10 mg od, started 6–8 hours after surgery and continuing for 35±4 days (extended prophylaxis). Mandatory, bilateral venography was conducted on day 36±4. The primary efficacy endpoint was the composite of any deep vein thrombosis (DVT), non-fatal pulmonary embolism (PE), and all-cause mortality. The main secondary efficacy endpoint was major VTE (the composite of proximal DVT, non-fatal PE, and VTE-related death). Safety endpoints included the incidence of major and non-major bleeding. Results: The incidence of the primary efficacy endpoint was significantly reduced with extended thromboprophylaxis with rivaroxaban compared with short-term enoxaparin (2.0% and 9.3%, respectively; p< 0.001; relative risk reduction [RRR] 79%), as was major VTE (0.6% versus 5.1%; p< 0.001; RRR 88%). The incidence of major bleeding was the same in both groups (0.1%). Non-major bleeding was reported in 6.5% of patients who received extended thromboprophylaxis with rivaroxaban and in 5.5% of those treated with short-term enoxaparin. Conclusion: Extended duration thromboprophylaxis with rivaroxaban is both significantly more effective and adds no disadvantage, in terms of bleeding, when compared with short-term prophylaxis. These data suggest that extended thromboprophylaxis provides substantial benefits to patients undergoing THR and rivaroxaban provides a safe and effective option for this strategy

Purpose: Thromboprophylaxis is recommended for at least 10 days and up to 35 days following total hip replacement (THR). Rivaroxaban is an oral, direct Factor Xa inhibitor in advanced clinical development that showed promise in early clinical trials. The purpose of this randomized, double-blind, double-dummy, phase III study was to compare the efficacy and safety of oral rivaroxaban with subcutaneous enoxaparin for 5 weeks, to prevent venous thromboembolism (VTE) in patients undergoing primary THR. Method: Patients received 10 mg rivaroxaban orally 6–8 hours after surgery and once daily thereafter, or 40 mg enoxaparin subcutaneously the evening before surgery (restarting 6–8 hours after surgery), and continued once daily. Thromboprophylaxis was administered for 35±4 days, and mandatory, bilateral venography was conducted the next day. The primary efficacy endpoint was the composite of any deep vein thrombosis (DVT), non-fatal pulmonary embolism (PE), and all-cause mortality. The primary efficacy analysis was a test for non-inferiority, followed by a test for superiority. Safety endpoints included major and non-major bleeding during the active treatment period. Results: A total of 4541 patients were randomized to receive rivaroxaban or enoxaparin. Rivaroxaban significantly reduced the incidence of the composite of DVT, PE, and all-cause mortality compared with enoxaparin (1.1% vs 3.7%, respectively; p< 0.001; relative risk reduction [RRR] 70%). Rivaroxaban also significantly reduced the incidence of major VTE compared with enoxaparin (0.2% vs 2.0%, respectively; p< 0.001; RRR 88%). There were no significant differences in the incidence of major bleeding (0.3% vs 0.1%; p=0.178) or non-major bleeding (5.8% vs 5.8%; p=1.000) between rivaroxaban and enoxaparin, respectively. There was no evidence of cardiac or liver safety issues. Conclusion: Oral, once-daily rivaroxaban was significantly more effective than subcutaneous, once-daily enoxaparin for extended thromboprophylaxis following THR. Rivaroxaban was not associated with an increased risk of bleeding and had a similar safety profile to enoxaparin. This trial demonstrated the efficacy and safety of a fixed, unmonitored dose of an oral, direct Factor Xa inhibitor – rivaroxaban – for extended thromboprophylaxis after THR

Purpose: Venous thromboembolism (VTE) is a common, potentially fatal complication of major orthopaedic surgery. Pharmacologic thromboprophylaxis is recommended following total hip replacement (THR) for a minimum of 10 days, and up to 35 days. However, its extended use is not accepted universally – an effective, safe and convenient, oral anticoagulant would improve implementation of these recommendations. This study was conducted to compare short-term thromboprophylaxis with enoxaparin and extended thromboprophylaxis with the novel, oral, direct Factor Xa inhibitor rivaroxaban after THR. This was the largest, prospective, randomized clinical trial conducted to date for the evaluation of the risk/benefit of extended duration thromboprophylaxis. Method: In this global, double-blind trial, 2509 patients undergoing THR were randomized to receive either subcutaneous enoxaparin 40 mg once daily (od), beginning the evening before surgery and continued for 10–14 days, followed by placebo until day 35±4 (short-term prophylaxis); or oral rivaroxaban 10 mg od beginning 6–8 hours after surgery and continuing for 35±4 days (extended prophylaxis). Mandatory, bilateral venography was conducted on day 36±4. The primary efficacy endpoint was the composite of any deep vein thrombosis (DVT), non-fatal pulmonary embolism (PE), and all-cause mortality. The main secondary efficacy endpoint was major VTE; the composite of proximal DVT, non-fatal PE, and VTE-related death. Safety endpoints included the incidence of major and non-major bleeding. Results: Extended thromboprophylaxis with rivaroxaban significantly reduced the incidence of both the primary efficacy endpoint (2.0% versus 9.3%, respectively; p< 0.001; relative risk reduction [RRR] 79%) and major VTE (0.6% versus 5.1%, respectively; p< 0.001; RRR 88%), compared with short-term enoxaparin. The incidence of major bleeding was 0.1% in patients receiving either extended or short-term thromboprophylaxis. Non-major bleeding was reported in 6.5% of patients receiving extended prophylaxis with rivaroxaban and 5.5% of those receiving short-term enoxaparin. Conclusion: Extended duration thromboprophylaxis with rivaroxaban was significantly more effective than short-term enoxaparin for the prevention of VTE in patients undergoing THR. Both regimens were associated with a similar incidence of bleeding. Extended thromboprophylaxis provides substantial benefits for patients undergoing THR and rivaroxaban provides a safe and effective option for this strategy

Background. Thromboembolic disease is a common complication of total hip replacement (THR). The administration of postoperative anticoagulants is therefore highly recommended. The purpose of this study was to compare rivaroxaban with fondaparinux with regards to their safety and effectiveness for the prevention of venous thromboembolic events (VTE) after THR. Methods. We conducted an independent prospective study comparing VTE prevention strategies in two successive series of patients (Groups A and B) undergoing elective unilateral THR. Group A (n=253) received fondaparinux daily 2.5 mg for 10 days, followed by tinzaparin 4500 IU daily for one month. Group B (n=229) received 10 mg rivaroxaban daily for 40 days without platelet monitoring. All surgeries were performed by a single surgeon under general anesthesia using an active blood transfusion-sparing plan. In the absence of contraindications, patients received intra-operative administration of tranexamic acid to reduce postoperative bleeding. Preoperative and postoperative hemoglobin levels were recorded at regular intervals. Bleeding events were documented. The bleeding index was calculated by adding the number of red blood cell units and the difference in the hemoglobin level (in g/dL) between the first morning after the day of surgery and the seventh postoperative day (POD 7). After 5 to 10 days, all patients underwent bilateral lower-extremity duplex ultrasonography to screen for deep venous thrombi. Any clinical symptoms of pulmonary embolism were evaluated with spiral computed tomography lung scans. Clinical evaluation to look for evidence of deep venous thrombi and pulmonary emboli was performed at eight weeks postoperatively. Results. Baseline characteristics between the two groups were comparable. The rate of major bleeding events, proximal deep venous thrombi, and pulmonary emboli was nil in each group. The incidence of blood transfusion was 0.8% in Group A (2 of 253 hips) and 0.4% (1 of 229 hips) in Group B (p=1.0). The bleeding index analysis excluded 8 hips for which the hemoglobin value at POD 7 was not measured. The bleeding index was 1.03 (standard deviation, 0.88) in Group A and 0.8 (standard deviation, 0.80) in Group B (p<0.001). The incidence of bleeding index >2 was 10.5% (27 of 247 hips) in Group A and 3% (7 of 227 hips) in Group B (p<0.001). Discussion. We compared two series of patients treated with THR undertaken with postoperative anticoagulation to prevent VTE. The high level of success these anticoagulant treatments had at preventing VTE in our series could be attributed at least partially to the combination of an active blood-sparing transfusion plan with the use of anticoagulant molecules reported in the literature to be quite potent. Conclusions. This prospective study comparing two anticoagulant regimens in patients treated with THR did not detect any difference with regards to the efficacy of the treatments, although there was significantly less bleeding index in patients who received rivaroxaban

BACKGROUND: Oral DVT prophylaxis not requiring monitoring is an advantage in orthopaedic patients. Dabigatran etexilate is an oral direct thrombin inhibitor undergoing evaluation for the prevention of venous thromboembolic events (VTE) following orthopaedic surgery. METHODS: In a phase III, multicenter, non-inferiority, double-blind study, patients undergoing total knee replacement were randomized to 3 treatments. The patients received 8±2 days of oral dabigatran etexilate, 150 or 220 mg once daily starting with a half dose (i.e.75 or 110 mg) 1–4 hours after surgery, or subcutaneous enoxaparin 40 mg once daily starting 12 hours prior to surgery. The primary efficacy outcome was the composite of total VTE and all causes of mortality during the treatment period. All efficacy and safety outcome events were adjudicated by blinded independent committees. RESULTS: Efficacy could be evaluated for 1541 (75%) treated and operated patients. Total VTE and death occurred in 40.5%, 36.4% and 37.7% of patients assigned to dabigatran etexilate 150 or 220mg once daily or enoxaparin, respectively. Proximal DVT and/ or PE occurred in 3.8%, 2.6% and 3.5% of patients receiving dabigatran 150 or 220mg or enoxaparin, respectively. Three deaths occurred during the treatment period, one in each of the treatment groups. Safety was evaluated for all 2076 patients receiving study treatment. The rate of major bleeding was 1.3%, 1.5% and 1.3% of patients receiving dabigatran 150 or 220mg or enoxaparin. Elevated LFTs (ALT > 3xULN) occurred in 3.7%, 2.8% and 4.0% of the patients treated with 150 and 220 mg dabigatran or enoxaparin during the study. A temporary rise in LFTs was observed during the follow-up period in 0.5% of the patients who had received dabigatran and in 0.4% of the patients who had received enoxaparin. CONCLUSIONS: Non-inferiority for the primary efficacy endpoint was met for both doses of dabigatran etexilate compared to enoxaparin. There was no difference in bleeding rates between the treatment groups. Oral administration of dabigatran etexilate once daily, given early in the postoperative period, was effective and safe for the prevention of total VTE in patients undergoing total knee replacement surgery

Introduction: Four randomized, double-blind phase III studies (RECORD1–4) investigated the oral, direct Factor Xa inhibitor rivaroxaban for the prevention of venous thromboembolism (VTE) after elective total hip and total knee arthroplasty (THA and TKA). Patients (N=12,729) were randomized to receive oral rivaroxaban 10 mg once daily, or subcutaneous enoxaparin 40 mg once daily (RECORD1–3), or 30 mg twice daily (RECORD4). Those undergoing THA received rivaroxaban or enoxaparin for 31–39 days in RECORD1, and rivaroxaban for 31–39 days or enoxaparin for 10–14 days followed by placebo in RECORD2. In RECORD3 and 4 (TKA), prophylaxis was for 10–14 days. Methods: A prespecified pooled analysis of all four studies evaluated the effect of rivaroxaban on the composite of symptomatic VTE and all-cause mortality, and bleeding, relative to enoxaparin. The present subgroup analysis investigated potential drug–drug interactions with concomitant non-steroidal anti-inflammatory drugs (NSAIDs) or acetylsalicylic acid (ASA) – commonly used pain medications known to affect bleeding risk. The risk of on-treatment bleeding in the total study duration pool of all four RECORD studies was investigated. These prespecified analyses focused on on-treatment, adjudicated bleeding events, any bleeding, and the composite of major bleeding and clinically relevant non-major bleeding – after the first tablet intake (rivaroxaban or matching placebo). Co-medication use was evaluated over time. Relative bleeding rates with and without co-medication were calculated separately for the rivaroxaban and enoxaparin/placebo groups. Time after surgery (day of surgery was day 1) was stratified into three periods (days 1–3, days 4–7 and day 7 up to 2 days after the last dose), based on the decreasing risk with time of a first bleeding event after surgery and because prevalence of co-medication use can vary over time. Bleeding rates were recorded for each time period over the at-risk period (the day of surgery until the last day of double-blind study medication intake +2 days or until initial event onset). The ratio of the bleeding rate for co-medication exposed vs unexposed patient-days in the rivaroxaban group was compared with the corresponding rate ratio for the enoxaparin/placebo group for bleeding events (Mantel–Haenszel methods). Results: Concomitant use of ASA in the rivaroxaban groups showed rate ratios similar to those in the enoxaparin/placebo group (1.32 and 1.40, respectively, for any bleeding). Rate ratios were also similar with concomitant use of NSAIDs (1.22 in both groups, for any bleeding). Conclusion: In the RECORD1–4 subanalysis, there was no indication of increased bleeding associated with the use of these co-medications in patients taking rivaroxaban, compared with enoxaparin

Purpose: Thromboembolic events, such as deep vein thrombosis (DVT) and pulmonary embolism (PE), are a serious risk after major orthopaedic surgery. BAY 59-7939 is a novel, oral, direct Factor Xa inhibitor in clinical development for the prevention and treatment of thromboembolic disorders. The efficacy and safety of BAY 59-7939 for thromboprophylaxis have been determined relative to enoxaparin in two clinical trials, one after elective total hip replacement surgery, and one after elective total knee replacement surgery. This pre-specified analysis combines data from two multicenter, multinational, double-blind, dose-ranging studies; the hip surgery trial was performed in Europe, and the knee surgery trial in North America. Methods: Patients (N=1343) were randomized to oral BAY 59-7939 at 2.5, 5, 10, 20, or 30 mg twice daily (bid), or subcutaneous enoxaparin (40 mg once daily starting 12 hours before hip surgery, or 30 mg bid starting 12 hours after knee surgery), continuing until mandatory bilateral venography was performed 5–9 days after surgery. The primary efficacy endpoint was a composite of DVT, PE, and all-cause mortality. The primary safety endpoint was major, post-operative bleeding. Results: The primary efficacy endpoint occurred in 21.6%, 22.9%, 16.1%, 24.4%, and 19.3% of patients receiving BAY 59-7939 2.5, 5, 10, 20, and 30 mg bid, respectively, and 27.8% receiving enoxaparin (n=914). No significant dose–response relationship for efficacy was observed with BAY 59-7939 (P=0.39); this was potentially due to the efficacy achieved with the lower BAY 59-7939 doses. A significant dose–response relationship was observed for major, post-operative bleeding with BAY 59-7939 (P< 0.001), which occurred in 0.9%, 1.3%, 2.1%, 3.9%, and 7.0% of patients receiving BAY 59-7939 2.5, 5, 10, 20, and 30 mg bid, respectively, and 1.7% of patients receiving enoxaparin (n=1317). Conclusions: This analysis showed that BAY 59-7939 has a wide therapeutic window for the prevention of VTE following major orthopaedic surgery, and, at doses of 2.5–10 mg bid, has similar efficacy and safety to the enoxaparin regimens. Funding: Commerical funding. Funding Parties: This study was sponsored by Bayer HealthCare AG

Rivaroxaban is a novel, oral, once-daily, direct Factor Xa inhibitor in advanced development for the prevention and treatment of venous thromboembolism (VTE). This study analysed the potential economic benefit attributable to the use of oral rivaroxaban relative to subcutaneous enoxaparin for extended VTE prophylaxis (35±4 days) after total hip replacement (THR). In RECORD1, rivaroxaban reduced the incidence of the composite primary efficacy endpoint (total VTE, including all-cause mortality) by 70%, compared with enoxaparin (p< 0.001). Symptomatic VTE occurred in 0.3% and 0.5% (p=0.22) of patients receiving rivaroxaban and enoxaparin, respectively. Major bleeding was low and similar in both groups: 0.3% and 0.1% (p=0.18), respectively. Potential savings associated with oral rivaroxaban were based on any reduction in the incidence of symptomatic VTE events, and reduced administration and monitoring costs. Analyses for both the US and the UK included only non-drug costs incurred by the healthcare sector. It was assumed that nurses spent 3 minutes/day administering enoxaparin and training patients to self-inject; assumed duration of hospital stay was 5 days. UK costs (based on the 2007 NICE Guidelines) also included full blood counts (FBCs) every 3 days, for up to 14 days, in patients receiving enoxaparin. Two analyses were performed: one assumed no difference in the occurrence of symptomatic VTE between treatments; the other assumed that the observed difference was real, but did not reach statistical significance. In the first analysis, assuming no difference in symptomatic VTE incidence, the total resource cost in the US was $46/patient for enoxaparin and $42.5/patient for rivaroxaban: a saving of $3.5/patient. For the UK, the total resource cost was £33/patient for enoxaparin and £7.5/per patient for rivaroxaban: a saving of £25.5/ patient. Savings were driven by reduced monitoring (FBCs) and administration costs. In the second analysis, assuming the observed difference in symptomatic VTE incidence was real, the US total resource cost was $57/patient for enoxaparin and $42.5/patient for rivaroxaban: a saving of $14.5/patient. For the UK, the total resource cost was £30/patients for enoxaparin and £7.5/patient for rivaroxaban: a saving of £22.5/patient. Savings were again driven by reduced monitoring and administration costs, and also reduced VTE incidence. Over 400,000 US patients undergo THR, and ~60,000 patients in England and Wales undergo THR annually. Thus, the potential cumulative cost savings with rivaroxaban are considerable

We evaluated the safety and efficacy of a multimodal approach for prophylaxis of thromboembolism after THA, which includes preoperative autologous blood donation; hypotensive epidural anesthesia; intravenous administration of heparin during surgery, before femoral preparation when the thrombogenesis is maximally activated; expeditious surgery, minimizing femoral vein occlusion and blood loss; pneumatic compression; and early mobilization after surgery. 1946 consecutive, non-selected patients (2016 THAs) who received multimodal thromboembolic prophylaxis were followed prospectively for 3 months. Only patients with history of thrombocytopenia (platelet count < 100.000) or adverse reaction to heparin were excluded. The average age was 65 years (14 to 93), ASA classification was 1 in 14%, 2 in 48%, 3 in 37% and 4 in 1% of patients. There was a history of DVT in 86 patients and PE in 35. After surgery, the patients also received pharmacologic prophylaxis for 6 weeks (aspirin 83%; warfarin 17%). The incidence of asymptomatic DVT assessed by ultrasound in the first 198 consecutive patients was 7.1% (14 of 198). The incidence of clinical DVT in the subsequent 1748 patients was 1.8% (32 of 1748). Symptomatic PE occurred in 0.56% (11 of 1946), none of them fatal. The rate of PE in patients receiving aspirin was 0.49% (8 of 1615) and warfarin 0.9% (3 of 331). There was 1 PE among 95 patients with a prior history of PE or DVT (1%). One morbidly obese patient died of a cardiac arrhythmia confirmed by autopsy. There was only one major bleeding complication: one patient with a history of coagulopathy developed hematuria requiring a bladder flush and five units of blood, with an uneventful recovery. No patients developed epidural hematoma following administration of intraoperative heparin. A multimodal approach to prevent thromboembolic disease, showed results that compare favorably with the literature, and with our historic control of 2592 THRs without intraoperative heparin (PE rate of 1%; 0.04% fatal). This multimodal approach appears safe and efficacious as thromboembolic prophylaxis. Our low rate of PE does not support routine anticoagulation prophylaxis with drugs with a significant risk of bleeding

Dabigatran etexilate (Pradaxa. ®. ) is an oral direct thrombin inhibitor that was recently approved in Europe and Canada for the prevention of venous thromboembolism (VTE) in patients undergoing elective total knee replacement or total hip replacement surgery. Two pivotal clinical trials, RE-MODEL (. Eriksson BI et al. . J Thromb Haemost. 2007. ; . 5. : . 2178. –2185. ) and RENOVATE (. Eriksson BI et al. . Lancet. 2007. ; . 370. : . 949. –956. ), studied the efficacy and safety of 220 mg and 150 mg dabigatran etexilate once daily compared with 40 mg subcutaneous enoxaparin. A post hoc pooled analysis was performed in elderly patients (> 75 years) since renal function gradually declines with age. The primary efficacy endpoint was total VTE and all cause mortality and the secondary efficacy endpoint was major VTE and VTE-related mortality. The primary safety endpoint was major bleeding events (MBE), including those occurring at the surgical site. All bleeding events were blindly adjudicated. Of the patients treated with 220 mg dabigatran etexilate (n=1825), 150 mg dabigatran etexilate (n=1866) and enoxaparin (n=1848), 883 patients (16%) were over 75 years. 73% of these elderly patients were evaluable for the primary efficacy endpoint and 75% were evaluable for the secondary efficacy endpoint. All patients > 75 years were evaluable for safety outcomes, including bleeding. The incidence of total VTE and all cause mortality was 20.8% (44/212), 22.6% (49/217), and 27.2% (58/213), respectively, in the three groups. A similar trend was observed for major VTE and VTE-related mortality: 220 mg dabigatran etexilate, 1.9% (4/216, p=0.045 vs enoxaparin using Fisher’s exact test); 150 mg dabigatran etexilate, 4.5% (10/221); enoxaparin, 6.0% (13/218). MBE occurred in 11 of the 295 elderly patients receiving 220 mg dabigatran etexilate (3.7%), 4 of the 282 elderly patients receiving 150 mg dabigatran etexilate (1.4%) and in 9 of the 306 elderly patients taking enoxaparin (2.9%). Notably, 6/11 MBE in the dabigatran 220 mg group and 2/4 MBE in the 150 mg group started before the first dose of treatment. We conclude that in elderly patients (> 75 years) undergoing hip or knee replacement surgery, oral 150 mg dabigatran etexilate exhibited a numerically favourable bleeding profile with no difference in efficacy compared with 40 mg enoxaparin. Because safety, particularly bleeding, is of paramount importance in the elderly, the 150 mg once daily dose of dabigatran etexilate is currently recommended by EMEA for this group

Dabigatran etexilate (Pradaxa. ®. ) is an oral direct thrombin inhibitor that was recently approved in Europe and Canada for the prevention of venous thromboembolism (VTE) in patients undergoing total knee arthroplasty (TKA) or total hip arthroplasty (THA) surgery. In the phase III studies, concomitant administration of selective nonsteroidal anti-inflammatory drugs (NSAIDs with t½≤12 hours) and acetylsalicylic acid (ASA; < 160 mg/day) was allowed during treatment with dabigatran etexilate or enoxaparin. Due to the potential additional anticoagulant activity of these concomitant therapies a separate post hoc analysis was conducted to investigate the bleeding risk in these patients. We analysed the pooled study population (8,135 patients) from the three phase III trials in THA and TKA surgery (RE-MOBILIZE, RE-MODEL and RE-NOVATE) for major bleeding events (MBE). All MBE, which included surgical site bleeds, were assessed by an independent, expert adjudication committee. We report the rates of MBE and odds ratios (with 95% confidence intervals [CI]) for comparison of the subgroup concomitantly treated with NSAID (or ASA) versus the subgroup of patients without concomitant antithrombotically active medication. The overall rate of MBE (with and without NSAIDs and ASA) was 1.4% [CI 1.0–1.9], 1.1% [0.7–1.5] and 1.4% [1.0–2.0] with dabigatran etexilate 220 mg, 150 mg, and enoxaparin, respectively. Of the total population, 57.4% of patients received concomitant antithrombotic treatment: 54.1% received NSAID and 4.7% received ASA. The MBE rate in patients receiving dabigatran etexilate or enoxaparin plus NSAIDs was similar to the rate in patients taking only dabigatran etexilate or enoxaparin; 1.5% vs. 1.4% [OR 1.05; 0.55–2.01] for dabigatran etexilate 220 mg, 1.1% vs. 1.0% [OR 1.19; 0.55–2.55] for dabigatran etexilate 150 mg, and 1.6% vs. 1.2% [OR 1.32; 0.67–2.57] for enoxaparin. A similar pattern was seen in patients concomitantly receiving ASA; in this small group only a few patients with MBE were observed: 2 (1.6%) in the dabigatran etexilate 220 mg group, 2 (1.6%) in the 150 mg group, and 4 (3.0%) in the enoxaparin group. No relevant differences in risk for MBE were detected between treatments by co-medication subgroup or within treatment groups when comparing patients receiving dabigatran etexilate or enoxaparin only versus those concomitantly receiving NSAIDs or ASA. In conclusion, patients concomitantly receiving dabigatran etexilate and NSAIDs (with t½ ≤12 hours) or ASA (< 160 mg/day) have a similar risk of MBE to patients taking only dabigatran etexilate. These data support the use of dabigatran etexilate for the prevention of VTE in patients after THA or TKA, when concomitant use of NSAIDs or ASA (< 160 mg/day) is required

Introduction: Rivaroxaban is a novel, oral, direct Factor Xa inhibitor for the prevention of venous thromboembolism (VTE) after total hip and knee arthroplasty (THA, TKA). The pivotal RECORD trials showed that 35 days’ rivaroxaban significantly reduced total VTE following THA versus both 35-day and 14-day enoxaparin regimens. Following TKA, 14 days’ rivaroxaban significantly reduced total and symptomatic VTE versus 14 days enoxaparin. Major bleeding was similar for rivaroxaban and enoxaparin. An economic model was developed based on these results to assess the cost-effectiveness of rivaroxaban relative to enoxaparin in Sweden. Methods: The incidence of clinical events and resulting consequences on resource use and quality of life were modelled for rivaroxaban and enoxaparin over 5 years. VTE incidence during the prophylaxis period was based upon RECORD2 (THA) and RECORD3 (TKA) and extrapolated out to 90 days following surgery based on published epidemiological data. These trials were used because they best reflect the treatment length currently applied in clinical practice in Sweden. Recurrent VTE and post-thrombotic syndrome (PTS) beyond 90 days were modelled from published clinical data. Literature indicates that 10% of enoxaparin patients require visits from a district nurse following hospital discharge to administer subcutaneous (sc) enoxaparin, a cost not incurred with oral rivaroxaban. The cost associated with clinical events (major bleed, VTE and PTS) and home care visit was derived from published Swedish sources and expressed in Swedish kroner (SEK). Rivaroxaban and enoxaparin costs were included. Results: In THA, 35 days’ rivaroxaban produced an additional cost (SEK 119 [€12.59] per patient) versus 14 days enoxaparin. However, rivaroxaban resulted in a gain of quality-adjusted life years (QALYs) and in fewer symptomatic events per patient relative to enoxaparin. This means an extra cost with rivaroxaban of SEK 29,378 (€3,109) per QALY gained and SEK 3,929 (€416) per symptomatic event avoided. Because the cost for treating a VTE range from SEK 12,000 to 30,000, it is less costly to avoid such an event by using rivaroxaban than treating it once it occurs. In TKA, 14 days’ rivaroxaban produced savings of SEK 873 (€92) per patient versus 14 days’ enoxaparin, as well as an improvement in QALYs and a reduction in symptomatic VTE events. Consequently, rivaroxaban was both more effective and less costly. Extensive sensitivity analyses showed that these results persist in a clear majority of situations. Conclusion: The economic analysis showed that by reducing VTE, and providing an oral alternative to sc enoxaparin, oral rivaroxaban has the potential to significantly improve health outcomes in Sweden at a slightly higher (in THA) or lower (in TKA) cost than existing VTE prophylaxis

Introduction Recent changes in the management of hip fracture surgery patients may have resulted in changes in the epidemiology of venous thromboembolism (VTE). We aimed to determine the incidence of and predictive risk factors for symptomatic VTE and mortality, and the use of VTE prophylaxis, in hip fracture surgery patients. Methods Hip fracture surgery patients were enrolled in 525 hospitals in France between October 1 and November 30, 2002 in this prospective, multicenter, epidemiological study. VTE was assessed by a critical events committee at 3 months. Risk factors were identified using logistic regression. Results Data were from 6860 (97%) of 7019 enrolled patients. Median age was 82 years and 76% were women. 47% were femoral neck and 53% trochanteric or subtrochanteric fractures. All were operated on (osteosynthesis 57%, half prosthesis 35% and THR 8%). Prophylaxis with a low-molecular-weight heparin (LMWH) was administered perioperatively in 97.6% and for at least four weeks in 69.5% (median prophylaxis duration: 6 weeks). The rate of symptomatic VTE at 3 months was 1.34% (95% CI: 1.04– 1.64). There were 16 PE (rate 0.25%) and 3 were fatal. The rate of major bleeding was 1.2%. At 6 months, 1006 patients (14.7%) were dead. Significant risk factors for symptomatic VTE were: history of VTE (OR 2.9), induction of anesthesia until arrival in the recovery room > 2 hrs (OR 2.5), and varicose veins/post-thrombotic syndrome (OR 2.2). LMWH prophylaxis significantly reduced the risk of symptomatic VTE (OR 0.2). Significant predictive factors for mortality were: cancer (OR 2.3), surgical complications requiring re-intervention (OR 1.8), confusion before fracture (OR 1.8), ASA score ≥3 (OR 1.7), BMI ≤18 kg/m2 (OR 1.6), congestive heart failure (OR 1.6), atrial fibrillation (OR 1.6) and age > 80 years (OR 1.1). Conclusions Extended LMWH prophylaxis is applied widely after hip fracture surgery in France. The current rate of postoperative VTE is low. However, a major change in the care of these patients is needed because of the high mortality rate

Aim: Mental disorder has been recognized as one of the troublesome factors in the perioperative management of the patients with total hip arthroplasty. However, precise clinical analysis regarding outcome of efficacy and complication in the surgery has not been reported in detail. Our institute has owed the treatment of the patients with various severe complications in the district of 1.2 million. The patients of hip disability with mental disorders have been introduced for the treatment and managed under co-operation with division of Psychiatry. This study focused on perioperative status and complications of the patients with mental disorders under went total hip arthroplasty. Materials and methods: Retrospective survey included consecutive 354 THAs of the 309 patients performed from January 1986 to December 2006. Reason for the surgery was due to dysplastic osteoarthritis; 251 cases (85.1 %), rheumatoid arthritis; 45 (14.6 %), idiopathic osteonecrosis of femoral head; 12 (3.9 %) and post-traumatic arthritis 1 (0.3 %). The mean age was 61.0 (29–83) years. The rate and status of the patients with mental disorders, their perioperative complications and hospitalization period were analyzed, and compared with those of the patients without disorders. Results: Fifteen patients with mental disorders (4.9 %) received THA and the mean age was 54.8 (34–76) years. Eleven patients (73.3 %) was due to dysplastic osteoarthritis, 3 (20.0 %) to osteonecrosis of the femoral head, and 1 (6.7 %) to rheumatoid arthritis. The disorder was categorized into mood disorder (7 cases), schizophrenia (6), somatoform disorder (1) and alcohol dependence (1). Pain relief was achieved and gait ability was improved in all the patients. Dislocation was found in 3 cases (20.0%), who were all dysplastic osteoarthritis, and which occurred after 8, 30, and 49 days, respectively. One patient had a possibility of implant malposition. Two-thirds was due to inactivity and/or impairments of attention influenced by the psychotic drugs, but not failed into recurrent type of dislocation. The rate was significantly higher than that of the patients without the disorders (2.3%), (p< 0.05). Infection, major bleeding, serious thrombo-embolitic events, and anesthetic complications were not found. Type of psychotropic drug was antideprssant (13 cases), antipsychotic (9), anticholinergic (5), antialcohl(3), antimanic(2) and antiepileptic (1). Their mean number of the drug type was 4.1 in the patients of mental disorders, 4.7 in the patients with dislocation and 3.9 without dislocation, which was significantly high in the patients with dislocation. P< 0.05. Hospitalization period of the patients was 37.2 (8–47) days, which was not significantly different from those of the patients without the disorders; 36.9 (10–94) days P=0.86. Discussion: Postsurgical dislocation was evident finding in the series of the patients with mental disorders. Two thirds seemed to be affected by the medicated drugs, but not failed into recurrent type. Other major complication was not experienced and the treatment was successfully achieved under management under co-operation with division of Psychiatry and rehabilitation unit. THA for the patients with mental disorders contributed to recovery of hip disability

Aims

The optimal management of an infrapopliteal deep venous thrombosis (IDVT) following total knee arthroplasty (TKA) remains unknown. The risk of DVT propagation and symptom progression must be balanced against potential haemorrhagic complications associated with administration of anticoagulation therapy. The current study reports on a cohort of patients diagnosed with IDVT following TKA who were treated with aspirin, followed closely for development of symptoms, and scanned with ultrasound to determine resolution of IDVT.

Aims

Malignancy and surgery are risk factors for venous thromboembolism (VTE). We undertook a systematic review of the literature concerning the prophylactic management of VTE in orthopaedic oncology patients.

Aims

Cementless primary total hip arthroplasty (THA) is associated with risks of bleeding and thromboembolism. Anticoagulants are effective as venous thromboprophylaxis, but with an increased risk of bleeding. Tranexamic acid (TXA) is an efficient antifibrinolytic agent, but the mode and timing of its administration remain controversial. This study aimed to determine whether two intravenous (IV) TXA regimens (a three-hour two-dose (short-TXA) and 11-hour four-dose (long-TXA)) were more effective than placebo in reducing perioperative real blood loss (RBL, between baseline and day 3 postoperatively) in patients undergoing THA who receive rivaroxaban as thromboprophylaxis. The secondary aim was to assess the non-inferiority of the reduction of blood loss of the short protocol versus the long protocol.

The number of arthroplasties being performed increases each year. Patients undergoing an arthroplasty are at risk of venous thromboembolism (VTE) and appropriate prophylaxis has been recommended. However, the optimal protocol and the best agent to minimise VTE under these circumstances are not known. Although many agents may be used, there is a difference in their efficacy and the risk of bleeding. Thus, the selection of a particular agent relies on the balance between the desire to minimise VTE and the attempt to reduce the risk of bleeding, with its undesirable, and occasionally fatal, consequences.

Acetylsalicylic acid (aspirin) is an agent for VTE prophylaxis following arthroplasty. Many studies have shown its efficacy in minimising VTE under these circumstances. It is inexpensive and well-tolerated, and its use does not require routine blood tests. It is also a ‘milder’ agent and unlikely to result in haematoma formation, which may increase both the risk of infection and the need for further surgery. Aspirin is also unlikely to result in persistent wound drainage, which has been shown to be associated with the use of agents such as low-molecular-weight heparin (LMWH) and other more aggressive agents.

The main objective of this review was to summarise the current evidence relating to the efficacy of aspirin as a VTE prophylaxis following arthroplasty, and to address some of the common questions about its use.

There is convincing evidence that, taking all factors into account, aspirin is an effective, inexpensive, and safe form of VTE following arthroplasty in patients without a major risk factor for VTE, such as previous VTE.

Cite this article: Bone Joint J 2017;99-B:1420–30.

Aims

The purpose of this article was to review the current literature pertaining to the use of mobile compression devices (MCDs) for venous thromboembolism (VTE) following total joint arthroplasty (TJA), and to discuss the results of data from our institution.

Aims

Prosthetic joint infection (PJI) remains a serious complication that is associated with high morbidity and costs. The aim of this study was to prepare a systematic review to examine patient-related and perioperative risk factors that can be modified in an attempt to reduce the rate of PJI.

Post-operative complications after total hip or knee replacement can delay recovery, prolong hospitalisation, increase rates of re-admission and, in the most severe cases, lead to long-term disability or even death. In this analysis of pooled data from four large, randomised, phase III clinical trials that compared the oral, direct Factor Xa inhibitor rivaroxaban with subcutaneous enoxaparin for the prevention of venous thromboembolism after total hip or knee replacement (n = 12 729), the incidence of complications, including bleeding and adverse events related to surgery (such as wound infection, wound dehiscence and haemarthrosis) are reported. Interventions and procedures relating to surgery are also compared between the groups. Bleeding events, including excessive wound haematoma and surgical-site bleeding, occurred at similar rates in the rivaroxaban and enoxaparin groups. Over the total study duration, adverse surgical events occurred at a similar rate in the rivaroxaban group compared with the enoxaparin group after total knee replacement (2.26% vs 2.69%, respectively) and total hip replacement (1.48% vs 1.65%, respectively). Blood loss, wound drainage and transfusion requirements were also similar between the two groups.

This analysis shows that the incidence of adverse surgical events with rivaroxaban was similar to enoxaparin.

In order to compare the effect of oral apixaban (a factor Xa inhibitor) with subcutaneous enoxaparin on major venous thromboembolism and major and non-major clinically relevant bleeding after total knee and hip replacement, we conducted a pooled analysis of two previously reported double-blind randomised studies involving 8464 patients. One group received apixaban 2.5 mg twice daily (plus placebo injection) starting 12 to 24 hours after operation, and the other received enoxaparin subcutaneously once daily (and placebo tablets) starting 12 hours (± 3) pre-operatively. Each regimen was continued for 12 days (± 2) after knee and 35 days (± 3) after hip arthroplasty. All outcomes were centrally adjudicated. Major venous thromboembolism occurred in 23 of 3394 (0.7%) evaluable apixaban patients and in 51 of 3394 (1.5%) evaluable enoxaparin patients (risk difference, apixaban minus enoxaparin, -0.8% (95% confidence interval (CI) -1.2 to -0.3); two-sided p = 0.001 for superiority). Major bleeding occurred in 31 of 4174 (0.7%) apixaban patients and 32 of 4167 (0.8%) enoxaparin patients (risk difference -0.02% (95% CI -0.4 to 0.4)). Combined major and clinically relevant non-major bleeding occurred in 182 (4.4%) apixaban patients and 206 (4.9%) enoxaparin patients (risk difference -0.6% (95% CI -1.5 to 0.3)).

Apixaban 2.5 mg twice daily is more effective than enoxaparin 40 mg once daily without increased bleeding.

Following the publication in 2007 of the guidelines from the National Institute for Health and Clinical Excellence (NICE) for prophylaxis against venous thromboembolism (VTE) for patients undergoing surgery, concerns were raised by British orthopaedic surgeons as to the appropriateness of the recommendations for their clinical practice. In order to address these concerns NICE and the British Orthopaedic Association agreed to engage a representative panel of orthopaedic surgeons in the process of developing expanded VTE guidelines applicable to all patients admitted to hospital. The functions of this panel were to review the evidence and to consider the applicability and implications in orthopaedic practice in order to advise the main Guideline Development Group in framing recommendations.

The panel considered both direct and indirect evidence of the safety and efficacy, the cost-effectiveness of prophylaxis and its implication in clinical practice for orthopaedic patients. We describe the process of selection of the orthopaedic panel, the evidence considered and the contribution of the panel to the latest guidelines from NICE on the prophylaxis against VTE, published in January 2010.

The June 2014 Hip & Pelvis Roundup³⁶⁰ looks at: Modular femoral necks: early signs are not good; is corrosion to blame for modular neck failures; metal-on-metal is not quite a closed book; no excess failures in fixation of displaced femoral neck fractures; noise no problem in hip replacement; heterotopic ossification after hip arthroscopy: are NSAIDs the answer?; thrombotic and bleeding events surprisingly low in total joint replacement; and the elephant in the room: complications and surgical volume.

The June 2015 Trauma Roundup³⁶⁰ looks at: HIV-related implant surgery in trauma; Major transfusion under the spotlight; Surgery and mortality in elderly acetabular fractures; Traction pin safety; Obesity and trauma; Salvage of acetabular fixation in the longer term

This study compared the quality of reduction and complication rate when using a standard ilioinguinal approach and the new pararectus approach when treating acetabular fractures surgically. All acetabular fractures that underwent fixation using either approach between February 2005 and September 2014 were retrospectively reviewed and the demographics of the patients, the surgical details and complications were recorded.

A total of 100 patients (69 men, 31 women; mean age 57 years, 18 to 93) who were consecutively treated were included for analysis. The quality of reduction was assessed using standardised measurement of the gaps and steps in the articular surface on pre- and post-operative CT-scans.

There were no significant differences in the demographics of the patients, the surgical details or the complications between the two approaches. A significantly better reduction of the gap, however, was achieved with the pararectus approach (axial: p = 0.025, coronal: p = 0.013, sagittal: p = 0.001).

These data suggest that the pararectus approach is at least equal to, or in the case of reduction of the articular gap, superior to the ilioinguinal approach.

This approach allows direct buttressing of the dome of the acetabulum and the quadrilateral plate, which is particularly favourable in geriatric fracture patterns.

Cite this article: Bone Joint J 2015;97-B:1271-8.

The August 2014 Research Roundup³⁶⁰ looks at: Antibiotic loaded ceramic of use in osteomyelitis; fibronectin implicated in cartilage degeneration; Zinc Chloride accelerates fracture healing in rats; advertisements and false claims; Net Promoter Score: substance or rhetoric?; aspirin for venous thromboembolism prophylaxis and dissection, stress and the soul.

The National Institute for Health and Clinical Excellence (NICE) has thus far relied on historical data and predominantly industry-sponsored trials to provide evidence for venous thromboembolic (VTE) prophylaxis in joint replacement patients. We argue that the NICE guidelines may be reliant on assumptions that are in need of revision. Following the publication of large scale, independent observational studies showing little difference between low-molecular-weight heparins and aspirin, and recent changes to the guidance provided by other international bodies, should NICE reconsider their recommendations?

Cite this article: Bone Joint Res 2014;3:146–9.

We compared thromboembolic events, major haemorrhage and death after total hip replacement in patients receiving either aspirin or low-molecular-weight heparin (LMWH). We analysed data from the National Joint Registry for England and Wales linked to an administrative database of hospital admissions in the English National Health Service. A total of 108 584 patients operated on between April 2003 and September 2008 were included and followed up for 90 days. Multivariable risk modelling and propensity score matching were used to estimate odds ratios (OR) adjusted for baseline risk factors. An OR <  1 indicates that rates are lower with LMWH than with aspirin. In all, 21.1% of patients were prescribed aspirin and 78.9% LMWH. Without adjustment, we found no statistically significant differences. The rate of pulmonary embolism was 0.68% in both groups and 90-day mortality was 0.65% with aspirin and 0.61% with LMWH (OR 0.93; 95% CI 0.77 to 1.11). With risk adjustment, the difference in mortality increased (OR 0.84; 95% CI 0.69 to 1.01). With propensity score matching the mortality difference increased even further to 0.65% with aspirin and 0.51% with LMWH (OR 0.77; 95% CI 0.61 to 0.98). These results should be considered when the conflicting recommendations of existing guidelines for thromboprophylaxis after hip replacement are being addressed.

Recent recommendations by the National Institute for Health and Care Excellence (NICE) suggest that all patients undergoing elective orthopaedic surgery should be assessed for the risk of venous thromboembolism (VTE).

Little is known about the incidence of symptomatic VTE after elective external fixation. We studied a consecutive series of adult patients who had undergone elective Ilizarov surgery without routine pharmacological prophylaxis to establish the incidence of symptomatic VTE.

A review of a prospectively maintained database of consecutive patients who were treated between October 1998 and February 2011 identified 457 frames in 442 adults whose mean age was 42.6 years (16.0 to 84.6). There were 425 lower limb and 32 upper limb frames. The mean duration of treatment was 25.7 weeks (1.6 to 85.3).

According to NICE guidelines all the patients had at least one risk factor for VTE, 246 had two, 172 had three and 31 had four or more.

One patient (0.23%) developed a pulmonary embolus after surgery and was later found to have an inherited thrombophilia. There were 27 deaths, all unrelated to VTE.

The cost of providing VTE prophylaxis according to NICE guidelines in this group of patients would be £89 493.40 (£195.80 per patient) even if the cheapest recommended medication was used.

The rate of symptomatic VTE after Ilizarov surgery was low despite using no pharmacological prophylaxis. This study leads us to question whether NICE guidelines are applicable to these patients.

Cite this article: Bone Joint J 2014;96-B:426–30.

Rivaroxaban has been recommended for routine use as a thromboprophylactic agent in patients undergoing lower-limb arthroplasty. However, trials supporting its use have not fully evaluated the risks of wound complications. This study of 1048 total hip/knee replacements records the rates of return to theatre and infection before and after the change from a low molecular weight heparin (tinzaparin) to rivaroxaban as the agent of chemical thromboprophylaxis in patients undergoing lower-limb arthroplasty. During a period of 13 months, 489 consecutive patients undergoing lower-limb arthroplasty received tinzaparin and the next 559 consecutive patients received rivaroxaban as thromboprophylaxis.

Nine patients in the control (tinzaparin) group (1.8%, 95% confidence interval 0.9 to 3.5) returned to theatre with wound complications within 30 days, compared with 22 patients in the rivaroxaban group (3.94%, 95% confidence interval 2.6 to 5.9). This increase was statistically significant (p = 0.046). The proportion of patients who returned to theatre and became infected remained similar (p = 0.10).

Our study demonstrates the need for further randomised controlled clinical trials to be conducted to assess the safety and efficacy of rivaroxaban in clinical practice, focusing on the surgical complications as well as the potential prevention of venous thromboembolism.

We report an audit of 208 patients with a mean age of 39 years (16 to 65) attending the Orthopaedic Assessment Unit at the Wellington Hospital between January 2006 and December 2007 with an injury of the tendo Achillis requiring immobilisation in a cast. Information on assessment of venous thromboembolism (VTE) risk, prophylactic measures and VTE events for all patients was obtained from the medical records. A VTE risk factor was documented in the records of three (1%) patients. One of the 208 patients received aspirin prophylaxis; none received low molecular weight heparin. In all, 13 patients (6.3%, 95% confidence interval 3.4 to 10.5) developed symptomatic VTE during immobilisation in a cast, including six with a distal deep-vein thrombosis (DVT), four with a proximal DVT, and three with a confirmed pulmonary embolus. This incidence of symptomatic VTE is similar to that reported following elective hip replacement.

We propose that consideration is given to VTE prophylaxis during prolonged immobilisation of the lower limbs in a cast, to ensure that the same level of protection is provided as for patients undergoing elective hip replacement.

The October 2012 Research Roundup³⁶⁰ looks at: whether you can escape your genes; oral prophylaxis for DVT; non-responders and the internet; metal-on-metal, mice and damaged livers; sleeping on the job; cartilage contact stress in the normal human hip; and a perfect reason to subscribe to 360.

The incidence of deep-vein thrombosis and the need for thromboprophylaxis following isolated trauma below the knee is uncertain. We have investigated this with a prospective randomised double-blind controlled trial using low molecular weight heparin with saline injection as placebo in patients aged between 18 and 75 years who had sustained an isolated fracture below the knee which required operative fixation. All patients had surgery within 48 hours of injury and were randomised to receive either the placebo or low molecular weight heparin for 14 days, after which they underwent bilateral lower limb venography, interpreted by three independent radiologists. Further follow-up was undertaken at two, six, eight and 12 weeks.

A total of 238 patients fulfilled all the inclusion criteria, with 127 in the low molecular weight heparin group and 111 in the placebo group, all of whom underwent bilateral venography. There was no statistically significant difference in the incidence of deep-vein thrombosis between those patients treated with low molecular weight heparin or the placebo (p = 0.22). The number of deep-vein thromboses in the two groups was 11 (8.7%) and 14 (12.6%), respectively. Age and the type of fracture were significantly associated with the rate of deep-vein thrombosis (p = 0.001 and p = 0.009, respectively) but gender, comorbidities and the body mass index were not.

The overall incidence of deep-vein thrombosis in this series was 11%. There was no clinical or statistical significant reduction in the incidence of deep-vein thrombosis with the use of thromboprophylaxis. However, we accept that owing to a cessation of funding, recruitment to this trial had to be ended prior to establishing the necessary sample size. Our results cannot, therefore, categorically exclude the possibility that low molecular weight heparin treatment could be beneficial. We recommend a further multicentre trial be undertaken to resolve this matter.

There is currently limited information available on the benefits and risks of extended thromboprophylaxis after hip fracture surgery. SAVE-HIP3 was a randomised, double-blind study conducted to evaluate the efficacy and safety of extended thromboprophylaxis with the ultra-low molecular-weight heparin semuloparin compared with placebo in patients undergoing hip fracture surgery. After a seven- to ten-day open-label run-in phase with semuloparin (20 mg once daily subcutaneously, initiated post-operatively), patients were randomised to once-daily semuloparin (20 mg subcutaneously) or placebo for 19 to 23 additional days. The primary efficacy endpoint was a composite of any venous thromboembolism (VTE; any deep-vein thrombosis and non-fatal pulmonary embolism) or all-cause death until day 24 of the double-blind period. Safety parameters included major and clinically relevant non-major bleeding, laboratory data, and treatment-emergent adverse events (TEAEs). Extended thromboprophylaxis with semuloparin demonstrated a relative risk reduction of 79% in the rate of any VTE or all-cause death compared with placebo (3.9% vs 18.6%, respectively; odds ratio 0.18 (95% confidence interval 0.07 to 0.45), p < 0.001). Two patients in the semuloparin group and none in the placebo group experienced clinically relevant bleeding. TEAE rates were similar in both groups. In conclusion, the SAVE-HIP3 study results demonstrate that patients undergoing hip fracture surgery benefit from extended thromboprophylaxis.

Cite this article: Bone Joint J 2013;95-B:459–66.

Using general practitioner records and hospital notes and through direct telephone conversation with patients, we investigated the accuracy of nine patient-reported complications gathered from a self-completed questionnaire after elective joint replacement surgery of the hip and knee. A total of 402 post-discharge complications were reported after 8546 elective operations that were undertaken within a three-year period. These were reported by 136 men and 240 women with a mean age of 71.8 years (34 to 93). A total of 319 reported complications (79.4%; 95% confidence interval 75.4 to 83.3) were confirmed to be correct. High rates of correct reporting were demonstrated for infection (94.5%) and the need for further surgery (100%), whereas the rates of reporting deep-vein thrombosis (DVT), pulmonary embolism, myocardial infarction and stroke were lower (75% to 84.2%). Dislocation, peri-prosthetic fractures and nerve palsy had modest rates of correct reporting (36% to 57.1%). More patients who had knee surgery delivered incorrect reports of dislocation (p = 0.001) and DVT (p = 0.013).

Despite these variations, it appears that post-operative complications may form part of a larger patient-reported outcome programme after elective joint replacement surgery.

Patients who have undergone total hip or knee replacement (THR and TKR, respectively) are at high risk of venous thromboembolism. We aimed to determine the time courses of both the incidence of venous thromboembolism and effective prophylaxis. Patients with elective primary THR and TKR were enrolled in the multi-national Global Orthopaedic Registry. Data on the incidence of venous thromboembolism and prophylaxis were collected from 6639 THR and 8326 TKR patients.

The cumulative incidence of venous thromboembolism within three months of surgery was 1.7% in the THR and 2.3% in the TKR patients. The mean times to venous thromboembolism were 21.5 days (sd 22.5) for THR, and 9.7 days (sd 14.1) for TKR. It occurred after the median time to discharge in 75% of the THR and 57% of the TKA patients who developed venous thromboembolism. Of those who received recommended forms of prophylaxis, approximately one-quarter (26% of THR and 27% of TKR patients) were not receiving it seven days after surgery, the minimum duration recommended at the time of the study.

The risk of venous thromboembolism extends beyond the usual period of hospitalisation, while the duration of prophylaxis is often shorter than this. Practices should be re-assessed to ensure that patients receive appropriate durations of prophylaxis.

We evaluated the safety and efficacy of total knee replacement in patients receiving continuous warfarin therapy.

We identified 24 consecutive patients receiving long-term warfarin therapy who underwent total knee replacement between 2006 and 2008 and compared them with a group of age- and gender-matched patients not on long-term anticoagulation. Primary observations were changes in haemoglobin, transfusion rates and complications. Secondary observations were fluctuations in the international normalised ratio (INR) and post-operative range of movement.

There was no significant difference between the two groups in pre- or post-operative haemoglobin, incidence of transfusion or incidence of post-operative complications. There were no surgical delays due to a high INR level. The mean change in INR during the peri-operative phase was minimal (mean 0.4; sd 0.7). There was no significant difference in the range of movement between the two groups after day two post-operatively.

Current American College of Chest Physicians guidelines recommend bridging therapy for high-risk patients receiving oral anticoagulation and undergoing major orthopaedic procedures. We have shown that a safe alternative is to continue the steady-state warfarin peri-operatively in patients on long-term anticoagulation requiring total knee replacement.

We performed a meta-analysis of modern total joint replacement (TJR) to determine the post-operative mortality and the cause of death using different thromboprophylactic regimens as follows: 1) no routine chemothromboprophylaxis (NRC); 2) Potent anticoagulation (PA) (unfractionated or low-molecular-weight heparin, ximelagatran, fondaparinux or rivaroxaban); 3) Potent anticoagulation combined (PAC) with regional anaesthesia and/or pneumatic compression devices (PCDs); 4) Warfarin (W); 5) Warfarin combined (WAC) with regional anaesthesia and/or PCD; and 6) Multimodal (MM) prophylaxis, including regional anaesthesia, PCDs and aspirin in low-risk patients. Cause of death was classified as autopsy proven, clinically certain or unknown. Deaths were grouped into cardiopulmonary excluding pulmonary embolism (PE), PE, bleeding-related, gastrointestinal, central nervous system, and others (miscellaneous). Meta-analysis based on fixed effects or random effects models was used for pooling incidence data.

In all, 70 studies were included (99 441 patients; 373 deaths). The mortality was lowest in the MM (0.2%) and WC (0.2%) groups. The most frequent cause of death was cardiopulmonary (47.9%), followed by PE (25.4%) and bleeding (8.9%). The proportion of deaths due to PE was not significantly affected by the thromboprophylaxis regimen (PA, 35.5%; PAC, 28%; MM, 23.2%; and NRC, 16.3%). Fatal bleeding was higher in groups relying on the use of anticoagulation (W, 33.8%; PA, 9.4%; PAC, 10.8%) but the differences were not statistically significant.

Our study demonstrated that the routine use of PA does not reduce the overall mortality or the proportion of deaths due to PE.

Exsanguination is the second most common cause of death in patients who suffer severe trauma. The management of haemodynamically unstable high-energy pelvic injuries remains controversial, as there are no universally accepted guidelines to direct surgeons on the ideal use of pelvic packing or early angio-embolisation. Additionally, the optimal resuscitation strategy, which prevents or halts the progression of the trauma-induced coagulopathy, remains unknown. Although early and aggressive use of blood products in these patients appears to improve survival, over-enthusiastic resuscitative measures may not be the safest strategy.

This paper provides an overview of the classification of pelvic injuries and the current evidence on best-practice management of high-energy pelvic fractures, including resuscitation, transfusion of blood components, monitoring of coagulopathy, and procedural interventions including pre-peritoneal pelvic packing, external fixation and angiographic embolisation.

Cite this article: Bone Joint J 2014; 96-B:1143–54.

Prophylaxis against venous thromboembolism after elective total hip replacement is routinely recommended. Our preference has been to use mechanical prophylaxis without anticoagulant drugs. A randomised controlled trial was performed to evaluate whether the incidence of post-operative venous thromboembolism was reduced by using pharmacological anticoagulation with either fondaparinux or enoxaparin in addition to our prophylactic mechanical regimen. A total of 255 Japanese patients who underwent primary unilateral cementless total hip replacement were randomly assigned to one of three postoperative regimens, namely injection of placebo (saline), fondaparinux or enoxaparin. There were 85 patients in each group. All also received the same mechanical prophylaxis during and after the operation, regardless of their assigned group. The primary measurement of efficacy was the presence of a venous thromboembolic event by day 11, defined as deep-vein thrombosis detected by ultrasonography, documented symptomatic deep-vein thrombosis or documented symptomatic pulmonary embolism. The duration of follow-up was 12 weeks.

The rate of venous thromboembolism was 7.2% with the placebo, 7.1% with fondaparinux and 6.0% with enoxaparin (p = 0.95 for the comparison of all three groups). Our study confirmed the effectiveness and safety of mechanical thromboprophylaxis without the use of anticoagulant drugs after total hip replacement in Japanese patients.

We present seven patients with recurrent haemarthroses after total knee arthroplasty, caused by an inherent platelet function defect. These patients developed painful knee swelling, persistent bleeding and/or wound breakdown, a platelet factor 3 availability defect being identified in all cases. Surgical exploration, with joint debridement, lavage and synovectomy, was performed in four patients who did not improve with conservative therapy. Histopathological examination of synovium revealed a focal synovial reaction with histiocytic infiltration, and occasional foreign-body giant cells. One patient required an early revision because of aseptic loosening of their tibial component. The condition was treated by single-donor platelet transfusions with good results. The diagnosis, management, and relevance of this disorder are discussed.

We report a retrospective review of the incidence of venous thromboembolism in 463 consecutive patients who underwent primary total hip arthroplasty (487 procedures). Treatment included both total hip replacement and hip resurfacing, and the patients were managed without anticoagulants. The thromboprophylaxis regimen included an antiplatelet agent, generally aspirin, hypotensive epidural anaesthesia, elastic compression stockings and early mobilisation. In 258 of these procedures (244 patients) performed in 2005 (cohort A) mechanical compression devices were not used, whereas in 229 (219 patients) performed during 2006 (cohort B) bilateral intermittent pneumatic calf compression was used.

All operations were performed through a posterior mini-incision approach. Patients who required anticoagulation for pre-existing medical problems and those undergoing revision arthroplasty were excluded. Doppler ultrasonographic screening for deep-vein thrombosis was performed in all patients between the fourth and sixth post-operative days. All patients were reviewed at a follow-up clinic six to ten weeks after the operation. In addition, reponse to a questionnaire was obtained at the end of 12 weeks post-operatively.

No symptomatic calf or above-knee deep-vein thrombosis or pulmonary embolism occurred. In 25 patients in cohort A (10.2%) and in ten patients in cohort B (4.6%) asymptomatic calf deep-vein thromboses were detected ultrasonographically. This difference was statistically significant (p = 0.03). The regimen followed by cohort B offers the prospect of a low incidence of venous thromboembolism without subjecting patients to the higher risk of bleeding associated with anticoagulant use.

Heterotopic ossification following joint replacement in the lower limb occurs in 3% to 90% of cases. Higher grades of heterotopic ossification can result in significant limitation of function and can negate the benefits of joint replacement. The understanding of the pathophysiology of this condition has improved in recent years. It would appear to be related to a combination of systemic and local factors, including over-expression of bone morphogenetic protein-4. There is currently little evidence to support the routine use of prophylaxis for heterotopic ossification in arthroplasty patients, but prophylaxis is recommended by some for high-risk patients. Radiotherapy given as one dose of 7 Gy to 8 Gy, either pre-operatively (< four hours before) or post-operatively (within 72 hours of surgery), appears to be more effective than indometacin therapy (75 mg daily for six weeks). In cases of prophylaxis against recurrent heterotopic ossification following excision, recent work has suggested that a combination of radiotherapy and indometacin is effective. Advances in our understanding of this condition may permit the development of newer, safer treatment modalities.

Our aim was to determine the total blood loss associated with surgery for fracture of the hip and to identify risk factors for increased blood loss. We prospectively studied 546 patients with hip fracture. The total blood loss was calculated on the basis of the haemoglobin difference, the number of transfusions and the estimated blood volume. The hidden blood loss, in excess of that observed during surgery, varied from 547 ml (screws/ pins) to 1473 ml (intramedullary hip nail and screw) and was significantly associated with medical complications and increased hospital stay. The type of surgery, treatment with aspirin, intra-operative hypotension and gastro-intestinal bleeding or ulceration were all independent predictors of blood loss.

We conclude that total blood loss after surgery for hip fracture is much greater than that observed intra-operatively. Frequent post-operative measurements of haemoglobin are necessary to avoid anaemia.