Total knee arthroplasty is a successful procedure with good long-term results. Studies indicate that 15% – 25% of patients are dissatisfied with their total knee arthroplasty. In addition, return to sports activities is significantly lower than total hip arthroplasty with 34% – 42% of patients reporting decreased sports participation after their total knee arthroplasties.

Poor outcomes and failures are often associated with technical errors. These include malalignment and poor ligament balancing. Malalignment has been reported in up to 25% of all revision knee arthroplasties, and instability is responsible for over 20% of failures. Most studies show that proper alignment within 3 degrees is obtained in only 70% – 80% of cases.

Navigation has been shown in many studies to improve alignment. In 2015, Graves examined the Australian Joint Registry and found that computer navigated total knee arthroplasty was associated with a reduced revision rate in patients under 65 years of age. Navigation can improve alignment, but does not provide additional benefits of ligament balance.

Robotic-assisted surgery can assist in many of the variables that influence outcomes of total knee arthroplasty including: implant positioning, soft tissue balance, lower limb alignment, proper sizing.

The data on robotic-assisted unicompartmental arthroplasty is quite promising. Cytech showed that femoral and tibial alignment were both significantly more accurate than manual techniques with three times as many errors with the manually aligned patients. Pearle, et al. compared the cumulative revision rate at two years and showed this rate was significantly lower than data reported in most unicompartmental series, and lower revision rates than both Swedish and Australian registries. He also showed improved satisfaction scores at two years.

Pagnano has noted that optimal alignment may require some deviation from mechanically neutral alignment and individualization may be preferred. This is also likely to be a requirement of more customised or bi-cruciate retaining implant designs. The precision of robotic surgery may be necessary to obtain this individualised component alignment.

While robotic total knee arthroplasty requires further data to prove its value, more precise alignment and ligament balancing is likely to lead to improved outcomes, as Pearl, et al. and the Australian registry have shown.

While it is difficult to predict the future at this time, I believe robotic-assisted total knee arthroplasty is the future and that future begins now.

Instability currently represents the most frequent cause for revision total knee replacement. Instability can be primary from the standpoint of inadequately performed collateral and/or posterior cruciate ligament balancing during primary total knee replacement or it may be secondary to malalignment/loosening which can develop later progressive instability. Revision surgery must take into consideration any component malalignment that may have primarily contributed to instability.

Care should be given to assessing collateral ligament integrity. This can be done during physical examination by radiological stress testing to see if the mediolateral stress of the knee comes to a good endpoint. If there is no sense of a palpable endpoint, then the surgeon must assume structural incompetency of the medial or lateral collateral ligament or both. In posterior cruciate retaining knees, anteroposterior instability must be assessed.

For instability, most revisions will require a posterior cruciate substituting design or a constrained condylar design that is unlinked. However, if the patient displays considerable global instability, a linked, rotating platform constrained total knee replacement design will be required. Recent data has shown that the rotating hinges work quite well in restoring stability to the knee with maintenance of the clinical results over a considerable length of time.

Intramedullary stems should be utilised in most cases when bone integrity is suspect and insufficient. Infection should be ruled out by aspiration and off of antibiotics prior to any revision operation, especially if loosening of the components represents the cause of instability. The surgeon should attempt to restore collateral ligament balance whenever possible as this yields the best clinical result.

Patellofemoral complaints are the common and nagging problem after total knee arthroplasty. Crepitus occurs in 5% to over 20% of knee arthroplasty procedures depending on the type of implant chosen. It is caused by periarticular scar formation with microscopic and gross findings indicating inflammatory fibrous hyperplasia.

Crepitus if often asymptomatic and not painful, but in some cases can cause pain. Patella “Clunk Syndrome” is less common and represents when the peripatella scarring is abundant and forms a nodule which impinges and “catches” on the implant's intercondylar notch. Patella Clunk was more common with early PS designs due to short trochlear grooves with sharp transition into the intercondylar notch. Clunks are very infrequent with modern PS implants. This syndrome has been reported in CR implants as well.

Thorough debridement of the synovium and scarring at the time of arthroplasty is thought to reduce the occurrence of crepitus and clunks. Larger patella with better coverage of the cut bone may also be helpful.

The diagnosis can be made on history and physical exam. X-rays are also helpful to assess patella tracking. MRI or ultrasound can be used to identify and confirm the diagnosis, but this is not mandatory.

Painful crepitus and clunk syndrome that fail conservative management of NSAIDS and physical therapy may require surgery. Both crepitus and clunk can be treated with arthroscopic removal of the peripatella scar. Patella maltracking should also be assessed and treated. While recurrence may occur, it is uncommon.

Deformity correction is a fundamental goal in total knee arthroplasty. Severe valgus deformities often present the surgeon with a complex challenge. These deformities are associated with abnormal bone anatomy, ligament laxity and soft tissue contractures. Distorted bone anatomy is due to bone loss on the lateral femoral condyle, especially posteriorly. To a lesser extent bone loss occurs from the lateral tibia plateau. The AP axis (Whiteside's Line) or epicondylar axis must be used as a rotational landmark in the severely valgus knee. Gap balancing techniques can be helpful in the severely valgus knee, but good extension balance must be obtained before setting femoral rotation with this technique. Coronal alignment is generally corrected to neutral or 2- to 3-degree overcorrection to mild mechanical varus to unload the attenuated medial ligaments.

The goal of soft tissue releases is to obtain rectangular flexion and extension gaps. Soft tissue releases involve the IT band, posterolateral corner/arcuate complex, posterior capsule, LCL, and popliteus tendon. Assessment of which structures is made and then releases are performed. In general, pie crust release of the IT band is sufficient for mild deformity. More severe deformities require release of the posterolateral corner / arcuate and posterior capsule. I prefer a pie crust technique, while Ranawat has described the use of electrocautery to perform these posterior/ posterolateral releases. In most cases the LCL is not released, however, this can be released from the lateral epicondyle, if necessary.

Good ligament balance can be obtained in most cases, however, some cases with severe medial ligament attenuation require additional ligament constraint such as a constrained condylar implant.

The decision to resurface the patella has been well studied. While regional differences exist, the overwhelming choice by most Surgeons in the United States is to resurface the patella. Data supports that this is the correct choice.

Articular cartilage on metal has not been shown to be a good long term bearing surface. Cushner et al. has also shown that cartilage in the arthritic knee has significant pathologic abnormalities. Patella surfacing has excellent long-term results with a low complication rate. Anterior knee pain is a common complaint after knee replacement and is even more common in TKA with un-resurfaced patella. Pakos et al. had more reoperations and greater anterior knee pain when the patella was NOT resurfaced. Parvizi et al. also found less patient satisfaction with un-resurfaced patellas. Meta-analysis results indicate higher revision rates with un-resurfaced patellas. Bilateral knee studies also favor resurfaced patella. Higher revision rates were also confirmed in the Swedish Registry with a 140% higher revision rate in TKA with un-resurfaced patellas In addition, second operations to resurface the patella often are unsuccessful at alleviating pain.

Surgeons who choose not to resurface the patella must accept that their patients will have the same or greater degree of anterior knee pain and a significantly greater risk for reoperation.

Deformity correction is a fundamental goal in total knee arthroplasty. Severe valgus deformities often present the surgeon with a complex challenge. These deformities are associated with abnormal bone anatomy, ligament laxity and soft tissue contractures. Distorted bone anatomy is due to bone loss on the lateral femoral condyle, especially posteriorly. To a lesser extent bone loss occurs from the lateral tibia plateau. The AP Axis (Whiteside's Line) or Epicondylar axis must be used as a rotational landmark in the severely valgus knee. Gap balancing techniques can be helpful in the severely valgus knee, but good extension balance must be obtained before setting femoral rotation with this technique. Coronal alignment is generally corrected to neutral or 2- to 3-degree overcorrection to mild mechanical varus to unload the attenuated medial ligaments.

The goal of soft tissue releases is to obtain rectangular flexion and extension gaps. Soft tissue releases involve the IT band, Posterolateral Corner/Arcuate Complex, Posterior Capsule, LCL, and Popliteus Tendon. Assessment of which structures is made and then releases are performed. In general Pie Crust release of the ITB is sufficient for mild deformity. More severe deformities require release of the Posterolateral Corner/Arcuate Complex and Posterior Capsule. I prefer a pie crust technique, while Ranawat has described the use of electrocautery to perform these posterior/ posterolateral releases. In most cases the LCL is not released, however, this can be released from the lateral epicondyle, if necessary.

Good ligament balance can be obtained in most cases, however, some cases with severe medial ligament attenuation require additional ligament constraint such as a constrained condylar implant.

The decision to resurface the patella has been well studied. While regional differences exist, the overwhelming choice by most surgeons in the United States is to resurface the patella. Data supports that this is the correct choice.

Articular cartilage on metal has not been shown to be a good long term bearing surface. Cushner et al has also shown that cartilage in the arthritic knee has significant pathologic abnormalities.

Patella surfacing has excellent long-term results with a low complication rate. Anterior knee pain is a common complaint after knee replacement and is even more common in TKA with unresurfaced patella. Pakos et al had more reoperations and greater anterior knee pain when the patella was NOT resurfaced. Parvizi et al also found less patient satisfaction with unresurfaced patellas.

Meta-analysis results indicate higher revision rates with unresurfaced patellas. Bilateral knee studies also favor resurfaced patella. Higher revision rates were also confirmed in the Swedish Registry with a 140% higher revision rate in TKA with unresurfaced patellas.

In addition second operations to resurface the patella often are unsuccessful at alleviating pain.

Surgeons who choose not to resurface the patella must accept that their patients will have the same or greater degree of anterior knee pain and a significantly greater risk for reoperation.

Introduction

Positioning of a femoral sizing guide has been cited as being a critical intraoperative step during measured-resection based TKA as it determines femoral component rotation. Consequently, modern femoral sizing guides permit surgeons to ‘dial in’ external rotation when placing the guide. Although this feature facilitates guide placement, its effect on posterior femoral condylar resection and flexion gap stability is unknown. This study examines the effect of rotation on posterior femoral condylar resection among different posterior-referencing TKA designs.

Introduction

Superficial wound complications can occur in up to 10% of total knee arthroplasty (TKA) patients and have been associated with deep infection. The ideal material for TKA closure should fulfill the following requirements: 1) fast intraoperative application, 2) minimal wound complications and discomfort, and 3) can be removed by patients without a home care visit. We present our experience with a novel, non-invasive, removable skin closure system compared to conventional staple closure.

Total knee arthroplasty has been shown to provide relief of pain and improved function; however studies have shown that younger active patients still note limitations in performing higher level activities such as dancing, golfing, skiing and gardening. Journey II BCS is designed to have physiological matching which more accurately reproduces the normal knee anatomy and kinematics. By providing more anatomic restoration of the articular geometry and substituting for both cruciate ligaments, Physiological Matching TKA has been shown, with in-vivo kinematic studies, to better reproduce the normal bending, rollback and rotational motions of knees.

Patient matched instruments are patient specific custom designed cutting blocks. These instruments utilise pre-operative MRI and full leg x-rays to design guides that will position the knee in the desired mechanical alignment. The purpose of these instruments is to increase efficiency and accuracy, and possibly reduce cost.

Efficiency occurs through the elimination of multiple steps compared to the standard operative technique. A single patient matched femoral guide is easily placed and can align the valgus angle with the mechanical axis, and determine the level of resection, rotation, size, and AP position of the implant. A single tibial instrument can determine tibial alignment, depth of resection, slope and rotation. Efficiency also results by eliminating the need for many standard instruments and trays. Implant size is determination pre-operatively so fewer implant trials are necessary.

In summary, this Physiological Matching TKA surgery combines Journey II BCS with patient specific instruments to optimise kinematics, fit and efficiency in order to improve outcomes and patient satisfaction.

Patellofemoral complaints are the common and nagging problem after Total Knee Arthroplasty. Crepitus occurs in 5% to over 20% of knee arthroplasty procedure depending on the type of implant chosen. It is caused by periarticular scar formation with microscopic and gross findings indicating inflammatory fibrous hyperplasia.

Crepitus if often asymptomatic and not painful, but in some cases can cause pain. Patella “Clunk Syndrome” is less common and represents a when the peripatella scarring is abundant and forms a nodule which impinges and “catches” on the implants intercondylar notch. Patella Clunk was more common with early PS designs due to short trochlear grooves with sharp transition into the intercondylar notch. Clunks are very infrequent with modern PS implants. This Syndrome has been reported in CR implants as well.

Thorough debridement of the synovium and scarring at the time of Arthroplasty is thought to reduce the occurrence of crepitus and clunks. Larger patella with better coverage of the cut bone may also be helpful.

The diagnosis can be made on history and physical exam. X-rays are also helpful to assess patella tracking. MRI or ultrasound can be used to identify and confirm the diagnosis but this is not mandatory.

Painful crepitus and clunk syndrome that fail conservative management of NSAIDS and physical therapy may require surgery. Both crepitus and clunk can be treated with arthroscopic removal of the peripatella scar. Patella maltracking should also be assessed and treated. While recurrence may occur it is uncommon.

Instability currently represents the most frequent cause for revision total knee replacement. Instability can be primary from the standpoint of inadequately performed collateral and/or posterior cruciate ligament balancing during primary total knee replacement or it may be secondary to malalignment secondary to loosening which can develop later progressive instability. Revision surgery must take into consideration any component malalignment that may have primarily contributed to instability.

Care should be given to assessing collateral ligament integrity. This can be done during physical examination by radiological stress testing to see if the mediolateral stress of the knee comes to a good endpoint. If there is no sense of a palpable endpoint, then the surgeon must assume structural incompetency of the medial or lateral collateral ligament or both. In posterior cruciate retaining knees, anteroposterior instability must be assessed.

For instability, must revisions will require a posterior cruciate substituting design or a constrained condylar design that are unlinked. However, if the patient displays considerable global instability, a linked, rotating platform constrained total knee replacement design will be required. Recent data has shown that the rotating hinges work quite well in restoring stability to the knee with maintenance of the clinical results over a considerable length of time.

During revision surgery, laminar spreaders may be utilised to assess the flexion and extension spaces after the tibial platform is restored. If a symmetric flexion and extension space are achieved, then the collateral ligaments are intact. Depending on the remaining existing bone stock, a posterior stabilised or constrained condylar unlinked prosthesis may be used for implantation. If there is considerable asymmetry or a large flexion/extension mismatch, then a rotating hinge design should be utilised.

Intramedullary stems should be utilised in most cases when bone integrity is suspect and insufficient. Currently, stems should be placed cementless to permit easier future revision. Cementing the stems is only recommended if there is lack of intramedullary isthmic support. However, revision of fully cemented revision implants may be quite difficult later.

Infection should be ruled out by aspiration off of antibiotics prior to any revision operation, especially if loosening of the components represents the cause of instability. The surgeon should attempt to restore collateral ligament balance whenever possible as this yields the best clinical result.

Deformity correction is a fundamental goal in Total Knee Arthroplasty. Severe valgus deformities often present the surgeon with a complex challenge. These deformities are associated with abnormal bone anatomy, ligament laxity and soft tissue contractures. Distorted bone anatomy is due to bone loss on the lateral femoral condyle, especially posteriorly. To a lesser extent bone loss occurs from the lateral tibia plateau. The AP Axis (Whiteside's Line) or Epicondylar axis must be used as a rotational landmark in the severely valgus knee. Gap balancing techniques can be helpful in the severely valgus knee, but good extension balance must be obtained before setting femoral rotation with this technique. Coronal alignment is generally corrected to neutral or 2 to 3 degree overcorrection to mild mechanical varus to unload the attenuated medial ligaments.

The goal of soft tissue releases is to obtain rectangular flexion and extension gaps. Soft tissue releases involve the IT band, Posterolateral corner/Accurate Complex, Posterior Capsule, LCL, and Popliteus Tendon. Assessment of which structures is made and then releases are performed. In general Pie Crust release of the ITB is sufficient for mild deformity. More severe deformities require release of the Posterolateral corner/Accurate Complex and Posterior Capsule. I prefer a pie crust technique, while Ranawat has described the use of electrocautery to perform these posterior/ posterolateral releases. In most cases the LCL is not released, however, this can be released from the lateral epicondyle if necessary.

Good ligament balance can be obtained in most cases, however, some cases with severe medial ligament attenuation require additional ligament constraint such as a constrained condylar implant.

Total Knee Arthroplasty has proven to be a successful procedure for improving pain and function. Long-term studies have shown survivorship to be 90% or greater at 20 years. Most patients in those studies were over 60 years old. There has been a large increase in patients under 60 years old who are undergoing knee arthroplasty. Younger patients have much greater demands on the artificial articular surfaces. The average 55 year old is likely to perform two to three time as many gait cycles as the average 65 or 70 year old. Long-term studies demonstrate that polyethylene wear is a major cause of long-term failure.

Newer bearing materials such as cross-linked polyethylenes show promise in reducing wear in THA and more recently in TKA. Femoral component material can significantly influence wear. Studies reveal that in vivo femoral component scratching significantly increases polyethylene wear.

Oxidised Zirconium (OxZr) has been shown to significantly reduce polyethylene wear in knee simulators. The ceramic surface has greater lubricity and is harder. We have examined the in vivo performance on Oxidised Zirconium in several studies. These studies reveal that the harder Oxidised Zirconium femoral surface is much more resistant to scratching than CrCo femurs. Retrieval analysis revealed a 12 fold increase in scratching of CrCo femoral components compared to OxZr. Profilometry analysis of matched pairs of femoral components demonstrates that the surfaces of the CrCo implants significantly roughen over time while the OxZr do not significantly change in vivo. These comparative studies also showed less damage to the tibial polyethylene bearings with the OxZr femoral components compared to CrCo.

Extending longevity of TKA requires improved materials to reduced wear. To optimise this, bearing surfaces must be coupled with improvements in both tibial polyethylene and femoral component materials.

Introduction

Oxidized zirconium (OxZr) is used as a ceramic surface for femoral components in total knee arthroplasty (TKA). The aim of this study was to investigate its performance by examining retrieved femoral components and their corresponding PE inserts in matched comparison with conventional chrome/cobalt/molybdenum alloy (CrCoMo).

Rivaroxaban is a novel, oral, once-daily, direct Factor Xa inhibitor in advanced clinical development. RECORD1 was a multinational, randomized, double-blind, double-dummy, phase III study investigating the efficacy and safety of extended thromboprophylaxis with rivaroxaban compared with subcutaneous enoxaparin following THR.

Patients (N=4541) were randomized to receive oral rivaroxaban 10 mg (6–8 hours after surgery and once daily thereafter) or subcutaneous enoxaparin 40 mg (administered the evening before surgery, 6–8 hours after surgery, and once daily thereafter) for 35±4 days. The primary efficacy outcome was the composite of deep vein thrombosis (DVT: symptomatic or detected by mandatory, bilateral venography if asymptomatic), non-fatal pulmonary embolism (PE), and all-cause mortality up to day 36±6. Major venous thromboembolism (VTE), the composite of any DVT, non-fatal PE and VTE-related death, was a secondary outcome. Safety endpoints included major and non-major bleeding while receiving study medication.

Rivaroxaban significantly reduced the incidence of the primary efficacy outcome compared with enoxaparin (1.1% vs 3.7%, respectively; p< 0.001; relative risk reduction [RRR] 70%). Rivaroxaban also significantly reduced the incidence of major VTE compared with enoxaparin (0.2% vs 2.0%, respectively; p< 0.001; RRR 88%). There were no significant differences in the incidence of major bleeding (0.3% vs 0.1%; p=0.178) or non-major bleeding (5.8% vs 5.8%; p=1.000) between rivaroxaban and enoxaparin, respectively. There was no evidence of liver safety issues associated with rivaroxaban.

Thromboprophylaxis with once-daily, oral rivaroxaban was significantly more effective than subcutaneous enoxaparin following THR without an increased risk of bleeding. This trial demonstrates the efficacy and safety of a fixed, unmonitored, once-daily dose of oral rivaroxaban for extended thromboprophylaxis after THR.

Rivaroxaban is a novel, oral, once-daily, direct Factor Xa inhibitor in advanced development for the prevention and treatment of venous thromboembolism (VTE). This study analysed the potential economic benefit attributable to the use of oral rivaroxaban relative to subcutaneous enoxaparin for extended VTE prophylaxis (35±4 days) after total hip replacement (THR). In RECORD1, rivaroxaban reduced the incidence of the composite primary efficacy endpoint (total VTE, including all-cause mortality) by 70%, compared with enoxaparin (p< 0.001). Symptomatic VTE occurred in 0.3% and 0.5% (p=0.22) of patients receiving rivaroxaban and enoxaparin, respectively. Major bleeding was low and similar in both groups: 0.3% and 0.1% (p=0.18), respectively.

Potential savings associated with oral rivaroxaban were based on any reduction in the incidence of symptomatic VTE events, and reduced administration and monitoring costs. Analyses for both the US and the UK included only non-drug costs incurred by the healthcare sector. It was assumed that nurses spent 3 minutes/day administering enoxaparin and training patients to self-inject; assumed duration of hospital stay was 5 days. UK costs (based on the 2007 NICE Guidelines) also included full blood counts (FBCs) every 3 days, for up to 14 days, in patients receiving enoxaparin.

Two analyses were performed: one assumed no difference in the occurrence of symptomatic VTE between treatments; the other assumed that the observed difference was real, but did not reach statistical significance.

In the first analysis, assuming no difference in symptomatic VTE incidence, the total resource cost in the US was $46/patient for enoxaparin and $42.5/patient for rivaroxaban: a saving of $3.5/patient. For the UK, the total resource cost was £33/patient for enoxaparin and £7.5/per patient for rivaroxaban: a saving of £25.5/ patient. Savings were driven by reduced monitoring (FBCs) and administration costs.

In the second analysis, assuming the observed difference in symptomatic VTE incidence was real, the US total resource cost was $57/patient for enoxaparin and $42.5/patient for rivaroxaban: a saving of $14.5/patient. For the UK, the total resource cost was £30/patients for enoxaparin and £7.5/patient for rivaroxaban: a saving of £22.5/patient. Savings were again driven by reduced monitoring and administration costs, and also reduced VTE incidence.

Over 400,000 US patients undergo THR, and ~60,000 patients in England and Wales undergo THR annually. Thus, the potential cumulative cost savings with rivaroxaban are considerable.

Introduction: Venous thromboembolism (VTE) is a common, potentially fatal complication of major orthopaedic surgery. Although pharmacological thromboprophylaxis is recommended following total hip replacement (THR) for a minimum of 10 days, and up to 35 days, its extended use is not universally accepted – an effective, safe and convenient, oral anticoagulant would improve implementation of these recommendations. This trial compared short-term thromboprophylaxis using enoxaparin with extended thromboprophylaxis using rivaroxaban – a once-daily, oral, direct Factor Xa inhibitor – after THR, in the largest, prospective, randomized clinical trial conducted to date for the evaluation of the risk/benefit of extended prophylaxis.

Method: In this global, double-blind trial, 2509 patients undergoing THR were randomized to receive either subcutaneous enoxaparin 40 mg once daily (od), started the evening before surgery and continued for 10–14 days, followed by placebo until day 35±4 (short-term prophylaxis), or oral rivaroxaban 10 mg od, started 6–8 hours after surgery and continuing for 35±4 days (extended prophylaxis). Mandatory, bilateral venography was conducted on day 36±4. The primary efficacy endpoint was the composite of any deep vein thrombosis (DVT), non-fatal pulmonary embolism (PE), and all-cause mortality. The main secondary efficacy endpoint was major VTE (the composite of proximal DVT, non-fatal PE, and VTE-related death). Safety endpoints included the incidence of major and non-major bleeding.

Results: The incidence of the primary efficacy endpoint was significantly reduced with extended thromboprophylaxis with rivaroxaban compared with short-term enoxaparin (2.0% and 9.3%, respectively; p< 0.001; relative risk reduction [RRR] 79%), as was major VTE (0.6% versus 5.1%; p< 0.001; RRR 88%). The incidence of major bleeding was the same in both groups (0.1%). Non-major bleeding was reported in 6.5% of patients who received extended thromboprophylaxis with rivaroxaban and in 5.5% of those treated with short-term enoxaparin.

Conclusion: Extended duration thromboprophylaxis with rivaroxaban is both significantly more effective and adds no disadvantage, in terms of bleeding, when compared with short-term prophylaxis. These data suggest that extended thromboprophylaxis provides substantial benefits to patients undergoing THR and rivaroxaban provides a safe and effective option for this strategy.

Introduction: After total hip replacement (THR), thromboprophylaxis for at least 10 days and for up to 35 days is recommended – yet a convenient, oral anticoagulant is not currently available. Rivaroxaban – a once-daily, oral, direct Factor Xa inhibitor with a predictable clinical profile – is in advanced clinical development. RECORD1, a multinational, randomized, double-blind, double-dummy, phase III study, compared once-daily oral rivaroxaban with subcutaneous enoxaparin for 5 weeks following THR.

Methods: In total, 4541 patients were randomized to receive oral rivaroxaban 10 mg (6–8 hours after surgery and once daily thereafter), or 40 mg enoxaparin (administered subcutaneously the evening before surgery, resumed 6–8 hours after surgery, and continued once daily). Thromboprophylaxis was administered for 35±4 days; mandatory, bilateral venography was conducted the next day. The primary efficacy endpoint was the composite of any deep vein thrombosis (DVT), nonfatal pulmonary embolism (PE), and all-cause mortality. Safety endpoints included major and non-major bleeding during the active treatment period.

Results: The incidence of the composite of DVT, PE, and all-cause mortality was significantly lower for rivaroxaban compared with enoxaparin (1.1% vs 3.7%, respectively; p< 0.001; relative risk reduction [RRR] 70%). The incidence of major VTE was also significantly lower for rivaroxaban compared with enoxaparin (0.2% vs 2.0%, respectively; p< 0.001; RRR 88%). There were no significant differences in the incidence of major bleeding (0.3% vs 0.1%; p=0.178) or non-major bleeding (5.8% vs 5.8%; p=1.000) between rivaroxaban and enoxaparin, respectively. There was no evidence of cardiac or liver safety issues.

Conclusions: Following THR, thromboprophylaxis with once-daily, oral rivaroxaban was shown to be significantly more effective than subcutaneous, once-daily enoxaparin – without an increased risk of bleeding. This trial demonstrates the efficacy and safety of oral rivaroxaban using a fixed, unmonitored, once-daily dose for extended thromboprophylaxis after THR.

Purpose: Thromboprophylaxis is recommended for at least 10 days and up to 35 days following total hip replacement (THR). Rivaroxaban is an oral, direct Factor Xa inhibitor in advanced clinical development that showed promise in early clinical trials. The purpose of this randomized, double-blind, double-dummy, phase III study was to compare the efficacy and safety of oral rivaroxaban with subcutaneous enoxaparin for 5 weeks, to prevent venous thromboembolism (VTE) in patients undergoing primary THR.

Method: Patients received 10 mg rivaroxaban orally 6–8 hours after surgery and once daily thereafter, or 40 mg enoxaparin subcutaneously the evening before surgery (restarting 6–8 hours after surgery), and continued once daily. Thromboprophylaxis was administered for 35±4 days, and mandatory, bilateral venography was conducted the next day. The primary efficacy endpoint was the composite of any deep vein thrombosis (DVT), non-fatal pulmonary embolism (PE), and all-cause mortality. The primary efficacy analysis was a test for non-inferiority, followed by a test for superiority. Safety endpoints included major and non-major bleeding during the active treatment period.

Results: A total of 4541 patients were randomized to receive rivaroxaban or enoxaparin. Rivaroxaban significantly reduced the incidence of the composite of DVT, PE, and all-cause mortality compared with enoxaparin (1.1% vs 3.7%, respectively; p< 0.001; relative risk reduction [RRR] 70%). Rivaroxaban also significantly reduced the incidence of major VTE compared with enoxaparin (0.2% vs 2.0%, respectively; p< 0.001; RRR 88%). There were no significant differences in the incidence of major bleeding (0.3% vs 0.1%; p=0.178) or non-major bleeding (5.8% vs 5.8%; p=1.000) between rivaroxaban and enoxaparin, respectively. There was no evidence of cardiac or liver safety issues.

Conclusion: Oral, once-daily rivaroxaban was significantly more effective than subcutaneous, once-daily enoxaparin for extended thromboprophylaxis following THR. Rivaroxaban was not associated with an increased risk of bleeding and had a similar safety profile to enoxaparin. This trial demonstrated the efficacy and safety of a fixed, unmonitored dose of an oral, direct Factor Xa inhibitor – rivaroxaban – for extended thromboprophylaxis after THR.