Richard J. Friedman

Two phase 3 trials compared 28–35 days of treatment with oral dabigatran 220 mg or 150 mg (RE-NOVATE) or 220 mg (RE-NOVATE II) once daily with subcutaneous enoxaparin 40 mg once daily for prevention of venous thromboembolism (VTE) after elective total hip arthroplasty. This prespecified pooled analysis compared the outcomes for the dabigatran 220 mg dose with enoxaparin, which included 4,374 patients. Total VTE (venographic and symptomatic) plus all-cause mortality (primary efficacy), major VTE (proximal deep vein thrombosis [DVT] or non-fatal pulmonary embolism) plus VTE-related death, and bleeding events were evaluated. Efficacy analysis was based on the modified intention-to-treat (ITT) population and safety analysis was based on all treated patients. The common risk difference (RD) for dabigatran versus enoxaparin was estimated using a fixed effects model. Total VTE and all-cause mortality occurred in 6.8 % (114/1,672) and 7.7 % (129/1,682) (RD:–0.8 %, 95 % confidence interval [CI] –2.6 to 0.9) for dabigatran and enoxaparin, respectively. Major VTE plus VTE-related mortality occurred in 2.7 % (46/1,714) and 4.0 % (69/1,711) (RD: –1.4 %, 95 % CI –2.6 to –0.2) of patients receiving dabigatran 220 mg and enoxaparin, respectively. Major bleeding occurred in 1.7 % (37/2,156) and 1.3 % (27/2,157) (RD: 0.5 %, 95 % CI –0.2 to 1.2), for dabigatran and enoxaparin respectively. Extended prophylaxis with oral dabigatran 220 mg once daily was as effective as enoxaparin 40 mg once daily in reducing the risk of total VTE and all-cause mortality after total hip arthroplasty, with a similar bleeding profile. The clinically relevant outcome of major VTE and VTE-related death was significantly reduced with dabigatran versus enoxaparin. NCT00657150 and NCT00168818

Tudies, we investigated whether allogeneic blood transfusion increases the risk of postoperative infection compared with autologous blood transfusion or no transfusion. Methods: A post hoc analysis of the pooled RECORD data stratified patients into three groups according to the type of blood transfusion that they received: no transfusion (n = 6313), autologous blood transfusion (n = 1902), and allogeneic blood transfusion with or without autologous blood transfusion (n = 3962). The types of postoperative infection were recorded and included lower or upper respiratory tract and lung infection, bone and joint infection, wound inflammation or infection, urinary tract infection, and other infections. Results: The rates of infection in patients receiving no transfusion or autologous blood transfusion were similar; therefore, data from these two groups were combined. The rate of any infection was 9.9% (392 of 3962) in patients receiving allogeneic blood transfusion and 7.9% (646 of 8215) in patients not receiving allogeneic blood transfusion with or without autologous blood transfusion (p = 0.003). The rates of lower or upper respiratory tract and lung infection (2.1% [eighty-five of 3962] versus 1.3% [109 of 8215]; p = 0.002) and of wound inflammation or infection (2.4% [ninety-four of 3962] versus 1.7% [138 of 8215]; p = 0.046) were significantly higher in patients receiving allogeneic blood transfusion compared with patients not receiving allogeneic blood transfusion. When comparing patients who had received allogeneic blood transfusion with those who had not received allogeneic blood transfusion, the rates of bone and joint infection (0.4% [fourteen of 3962] versus 0.2% [eighteen of 8215]; p = 0.056), of urinary tract infection (3.1% [123 of 3962] versus 2.5% [209 of 8215]; p = 0.551), and of other infections (3.0% [120 of 3962] versus 2.7% [225 of 8215]; p = 0.308) were not significantly different. Conclusions: The rates of any infection, lower or upper respiratory tract and lung infection, and wound inflammation or infection were significantly increased after elective total hip or total knee arthroplasty in patients receiving allogeneic blood transfusion compared with those receiving autologous blood transfusion or no blood transfusion. Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence....

: (1) venous thromboembolism (VTE), (2) bleeding, (3) other adverse events, and (4) infections during the early postoperative period (up to 6 to 8 weeks) after THA or TKA? Methods Data from the REgulation of Coagulation in ORthopaedic surgery to prevent Deep vein thrombosis and pulmonary embolism (RECORD) clinical trial program of rivaroxaban for prevention of VTE after THA or TKA were analyzed retrospectively. Data for 12,355 patients were reviewed to identify complication rates in morbidly obese patients (BMI ≥ 40 kg/m2) compared with patients with a BMI less than 40 kg/m2. Explorative analyses compared the rates of asymptomatic deep vein thrombosis (DVT), symptomatic DVT, symptomatic pulmonary embolism, bleeding, and other adverse events by BMI group. Results There were no significant differences in asymptomatic DVT, symptomatic DVT, symptomatic pulmonary embolism, or bleeding, but there were increases in other adverse events (including receipt of blood transfusion, erythema, peripheral edema, diarrhea, gastrointestinal or abdominal pain) and infections (including respiratory tract or lung infections, wound inflammation or infection, and extrasurgical-site infections), in patients with a BMI of 40 kg/m2 or greater compared with patients with a BMI less than 40 kg/m2. Conclusions After THA or TKA, morbid obesity is not associated with an increased risk of VTE or bleeding but is associated with increased early postoperative complications, including erythema, peripheral edema, diarrhea and gastrointestinal or abdominal pain, wound inflammation or infection, extrasurgical-site infections, and respiratory tract or lung infections. Level of Evidence Level III, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence....

With the volume of total hip arthroplasty (THA) procedures performed in the US projected to increase significantly over the next 2 decades, preventing postsurgical complications, such as venous thromboembolism (VTE), has become a critical factor in reducing morbidity and mortality in the orthopaedic setting. Anticoagulation has typically involved the use of subcutaneous agents such as low molecular weight heparin (LMWH) and fondaparinux or oral agents such as warfarin. Despite their efficacy, these agents all have substantial drawbacks and pose adherence challenges for patients and management challenges for orthopaedic surgeons and other providers. The next generation of anticoagulants, which includes the direct thrombin inhibitor dabigatran etexilate and the Factor Xa inhibitors, rivaroxaban, apixaban, and edoxaban, are being used to provide safe and effective oral agents that do not require routine monitoring. Phase III studies involving these agents have shown either noninferiority or superiority over LMWH and have a comparable safety profile.

Patients undergoing total hip or knee arthroplasty should receive anticoagulant therapy because of the high risk of venous thromboembolism. However, many are already taking non-steroidal anti-inflammatory drugs (NSAIDs) or acetylsalicylic acid (ASA) that can have antihaemostatic effects. We assessed the bleeding risk in patients treated with thromboprophylactic dabigatran etexilate, with and without concomitant NSAID or ASA. A post-hoc analysis was undertaken of the pooled data from trials comparing dabigatran etexilate (220 mg and 150 mg once daily) and enoxaparin. Major bleeding event (MBE) rates were determined and odds ratios (ORs) generated for patients who received study treatment plus NSAID (half-life ≤12 hours) or ASA (≤160 mg/day) versus study treatment alone. Relative risks were calculated for comparisons between treatments. Overall, 4,405/8,135 patients (54.1%) received concomitant NSAID and 386/8,135 (4.7%) received ASA.ORs for the comparison with/without concomitant NSAID were 1.05 (95% confidence interval [CI] 0.55–2.01) for 220 mg dabigatran etexilate; 1.19 (0.55–2.55) for 150 mg; and 1.32 (0.67–2.57) for enoxaparin. ORs for the comparison with/without ASA were 1.14 (0.26–5.03); 1.64 (0.36–7.49); and 2.57 (0.83–7.94), respectively. For both NSAIDs and ASA there was no significant difference in bleeding between patients with and without concomitant therapy in any treatment arm. Patients concomitantly taking NSAIDs or ASA have a similar risk of MBE to those taking dabigatran etexilate alone. No significant differences in MBE were detected between dabigatran etexilate and enoxaparin within comedication subgroups, suggesting that no increased major bleeding risk exists when dabigatran etexilate is administered with NSAID or ASA. Investigation performed at multiple centres participating in the RE-MODEL™, RE-NOVATE®, and RE-MOBILIZE® trials.

There has been a shift towards greater use of neuraxial over general anaesthesia for patients undergoing total hip or knee arthroplasty. Furthermore, suggestions that peripheral nerve block may reduce adverse effects have recently been put forward. Although older studies showed a reduction in venous thromboembolism (VTE) with neuraxial compared with general anaesthesia, this difference has not been confirmed in studies using effective current thromboprophylaxis. We used a large data set to investigate the pattern of anaesthesia usage, and whether anaesthesia type affects efficacy and bleeding outcomes of thromboprophylaxis overall, within each treatment group, or for the novel oral anticoagulant dabigatran etexilate versus enoxaparin.

The number of total hip and knee arthroplasties is increasing, with a consequent rise in the number of patients at risk of venous thromboembolism. Each such event is associated with the risk of morbidity and mortality, plus substantial healthcare costs. Consequently, the American College of Chest Physicians guidelines recommend low-molecular-weight heparins, fondaparinux or vitamin K antagonists (usually warfarin) after total hip and knee arthroplasty. However, such agents are also associated with healthcare costs for administration and monitoring. New oral anticoagulants in development may reduce post-arthroplasty symptomatic thromboembolic events and produce potential savings for the healthcare system. This brief article outlines such potential savings with rivaroxaban based on the results of the REgulation of Coagulation in ORthopaedic surgery to prevent Deep vein thrombosis and pulmonary embolism (RECORD) program.

Orthopedics | Orthopedic procedures such as total hip arthroplasty (THA) and total knee arthroplasty (TKA) are among the most beneficial operations in terms of patient outcome and satisfaction. However, THA and TKA patients have a high risk of postoperative venous thromboembolism (VTE), in the form of deep vein thrombosis (DVT) or pulmonary embolism (PE). It is essential for orthopedic surgeons to

Venous thromboembolism is a serious complication after total hip or knee surgery, and there is a well-established clinical need for thromboprophylaxis. However, in a large number of cases adequate administration of thromboprophylaxis does not seem to occur after total joint arthroplasty. A major challenge in the management of thromboprophylaxis is to balance the benefits of treatment with the risks, including bleeding complications. Another potential barrier to the optimal use of thromboprophylaxis could be the inconvenience of currently available agents. Many surgeons therefore adopt a conservative approach towards thromboprophylaxis. Simplifying therapy with more convenient, efficacious, and safe anticoagulants could change attitudes to anticoagulant use and improve adherence to thromboprophylactic guidelines.

Patients undergoing total hip or knee arthroplasty often sustain significant decreases in hemoglobin and hematocrit, despite modern techniques and shorter operating times. Reasons for the blood loss include raw bony surfaces, vascular inflammatory tissue, and fragile vessels in elderly patients. Acute postoperative anemia has numerous deleterious effects on patients, including delayed rehabilitation, exposure to allogeneic blood transfusions, higher complication rates, and increased pain. The ability to limit the amount of postoperative bleeding may reduce the amount of postoperative pain that patients experience, ultimately resulting in greater patient satisfaction and smoother postoperative rehabilitation. This article focuses on intraoperative techniques available to limit bleeding, thereby minimizing pain and the need for postoperative transfusion.