Aims. The aim of this study was to evaluate the healthcare costs and benefits of enoxaparin compared to aspirin in the prevention of symptomatic venous thromboembolism (VTE) after total hip arthroplasty (THA) or total knee arthroplasty (TKA) using data from the CRISTAL trial. Methods. This trial-based economic analysis reports value for money as incremental cost per quality-adjusted life-year (QALY) gained in 2022 Australian dollars, compared to a single threshold value of AUD$70,000 per QALY. Event costs were estimated based on occurrence of VTEs and bleeds, and on published guidelines for treatment. Unit costs were taken from Australian sources. QALYs were estimated using CRISTAL six-month follow-up data. Sensitivity analyses are presented that vary the cost of VTE treatment, and extend the analyses to two years. Results. The CRISTAL trial found that enoxaparin was more effective than aspirin in preventing symptomatic VTE within 90 days of THA or TKA (risk difference 1.97% (95% confidence interval (CI) 0.54% to 3.41%; p = 0.007)). The additional cost after a THA or TKA was AUD$83 (95% CI 68 to 97) for enoxaparin, and enoxaparin resulted in an additional 0.002 QALYs (95% CI -0.002 to 0.005). Incremental cost per QALY gained was AUD$50,567 (95% CI 15,513, dominated) for enoxaparin. We can be 60% confident that the incremental cost per QALY does not exceed the willingness-to-pay threshold of AUD$70,000. Increasing the cost of VTE treatment and extension of costs and consequences to two years suggested greater confidence that enoxaparin is good value for money (70% and 63% confidence, respectively). Conclusion. This analysis provides strong evidence that enoxaparin thromboprophylaxis following THA or TKA reduced VTEs, but weak evidence of net economic benefits over aspirin. If the value of avoiding VTEs is high, and there is a strong likelihood of VTE-related health impairments, we can be more confident that enoxaparin is cost-effective compared to aspirin. Cite this article: Bone Joint J 2024;106-B(6):589–595

In order to compare the effect of oral apixaban (a factor Xa inhibitor) with subcutaneous enoxaparin on major venous thromboembolism and major and non-major clinically relevant bleeding after total knee and hip replacement, we conducted a pooled analysis of two previously reported double-blind randomised studies involving 8464 patients. One group received apixaban 2.5 mg twice daily (plus placebo injection) starting 12 to 24 hours after operation, and the other received enoxaparin subcutaneously once daily (and placebo tablets) starting 12 hours (± 3) pre-operatively. Each regimen was continued for 12 days (. ± . 2) after knee and 35 days (. ± . 3) after hip arthroplasty. All outcomes were centrally adjudicated. Major venous thromboembolism occurred in 23 of 3394 (0.7%) evaluable apixaban patients and in 51 of 3394 (1.5%) evaluable enoxaparin patients (risk difference, apixaban minus enoxaparin, -0.8% (95% confidence interval (CI) -1.2 to -0.3); two-sided p = 0.001 for superiority). Major bleeding occurred in 31 of 4174 (0.7%) apixaban patients and 32 of 4167 (0.8%) enoxaparin patients (risk difference -0.02% (95% CI -0.4 to 0.4)). Combined major and clinically relevant non-major bleeding occurred in 182 (4.4%) apixaban patients and 206 (4.9%) enoxaparin patients (risk difference -0.6% (95% CI -1.5 to 0.3)). Apixaban 2.5 mg twice daily is more effective than enoxaparin 40 mg once daily without increased bleeding

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

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

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

Prophylaxis against venous thromboembolism after elective total hip replacement is routinely recommended. Our preference has been to use mechanical prophylaxis without anticoagulant drugs. A randomised controlled trial was performed to evaluate whether the incidence of post-operative venous thromboembolism was reduced by using pharmacological anticoagulation with either fondaparinux or enoxaparin in addition to our prophylactic mechanical regimen. A total of 255 Japanese patients who underwent primary unilateral cementless total hip replacement were randomly assigned to one of three postoperative regimens, namely injection of placebo (saline), fondaparinux or enoxaparin. There were 85 patients in each group. All also received the same mechanical prophylaxis during and after the operation, regardless of their assigned group. The primary measurement of efficacy was the presence of a venous thromboembolic event by day 11, defined as deep-vein thrombosis detected by ultrasonography, documented symptomatic deep-vein thrombosis or documented symptomatic pulmonary embolism. The duration of follow-up was 12 weeks. The rate of venous thromboembolism was 7.2% with the placebo, 7.1% with fondaparinux and 6.0% with enoxaparin (p = 0.95 for the comparison of all three groups). Our study confirmed the effectiveness and safety of mechanical thromboprophylaxis without the use of anticoagulant drugs after total hip replacement in Japanese patients

After total hip (THR) or knee replacement (TKR), there is still an appreciable risk of developing deep-vein thrombosis despite prophylaxis with low-molecular-weight heparin (LMWH). In a prospective, randomised study we examined the efficacy of LMWH in combination with intermittent pneumatic compression in patients undergoing primary unilateral THR or TKR. We administered 40 mg of enoxaparin daily to 131 patients combined with either the use of intermittent pneumatic compression or the wearing of graduated compression stockings. Compression ultrasonography showed no evidence of thrombosis after LMWH and intermittent pneumatic compression. In the group with LMWH and compression stockings the prevalence of thrombosis was 28.6% (40% after TKR, 14% after THR). This difference was significant (p < 0.0001). In the early post-operative phase after THR and TKR, combined prophylaxis with LMWH and intermittent pneumatic compression is more effective than LMWH used with graduated compression stockings

Aims

The aims of this study were to determine the indications and frequency of ordering a CT pulmonary angiography (CTPA) following primary arthroplasty of the hip and knee, and to determine the number of positive scans in these patients, the location of emboli and the outcome for patients undergoing CTPA.

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

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

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

Since the introduction of the National Institute for Health and Care Excellence (NICE) guidelines on thromboprophylaxis and the use of extended thromboprophylaxis with new oral agents, there have been reports of complications arising as a result of their use. We have looked at the incidence of wound complications after the introduction of dabigatran for thromboprophylaxis in our unit.

We investigated the rate of venous thromboembolism and wound leakage in 1728 patients undergoing primary joint replacement, both before and after the introduction of dabigatran, and following its subsequent withdrawal from our unit.

We found that the use of dabigatran led to a significant increase in post-operative wound leakage (20% with dabigatran, 5% with a multimodal regimen; p < 0.001), which also resulted in an increased duration of hospital stay. The rate of thromboembolism in patients receiving dabigatran was higher (1.3%) than in those receiving the multimodal thromboprophylaxis regimen, including low molecular weight heparin as an inpatient and the extended use of aspirin (0.3%, p = 0.047). We have ceased the use of dabigatran for thromboprophylaxis in these patients.

Cite this article: Bone Joint J 2014;96-B:122–6.

Tranexamic acid is a fibrinolytic inhibitor which reduces blood loss in total knee replacement. We examined the effect on blood loss of a standardised intravenous bolus dose of 1 g of tranexamic acid, given at the induction of anaesthesia in patients undergoing total hip replacement and tested the potential prothrombotic effect by undertaking routine venography. In all, 36 patients received 1 g of tranexamic acid, and 37 no tranexamic acid. Blood loss was measured directly per-operatively and indirectly post-operatively.

Tranexamic acid reduced the early post-operative blood loss and total blood loss (p = 0.03 and p = 0.008, respectively) but not the intraoperative blood loss. The tranexamic acid group required fewer transfusions (p = 0.03) and had no increased incidence of deep-vein thrombosis. The reduction in early post-operative blood loss was more marked in women (p = 0.05), in whom this effect was dose-related (r = −0.793).

Our study showed that the administration of a standardised pre-operative bolus of 1 g of tranexamic acid was cost-effective in reducing the blood loss and transfusion requirements after total hip replacement, especially in women.

We randomised 120 patients who were undergoing either primary total hip or knee arthroplasty to receive either ferrous sulphate or a placebo for three weeks after surgery. The level of haemoglobin and absolute reticulocyte count were measured at one and five days, and three and six weeks after operation. Ninety-nine patients (ferrous sulphate 50, placebo 49) completed the study. The two groups differed only in the treatment administered.

Recovery of level of haemoglobin was similar at five days and three weeks and returned to 85% of the pre-operative level, irrespective of the treatment group. A small, albeit greater recovery in the level of haemoglobin was identified at six weeks in the ferrous sulphate group in both men (ferrous sulphate 5%, placebo 1.5%) and women (ferrous sulphate 6%, placebo 3%). The clinical significance of this is questionable and may be outweighed by the high incidence of reported side effects of oral iron and the cost of the medication. Administration of iron supplements after elective total hip or total knee arthroplasty does not appear to be worthwhile.