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

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

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