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:
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
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),
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
The August 2023 Hip & Pelvis Roundup. 360. looks at: Using machine learning to predict venous thromboembolism and
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,
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
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
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
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
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
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
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
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
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
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
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
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
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).
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
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
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.
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
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
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).
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,
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
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
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
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
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
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
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
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
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
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
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,
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
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
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
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
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.
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
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
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