Chemical prophylaxis is known to reduce the venographic prevalence of deep-vein thrombosis (DVT) after total knee replacement (TKR), but it is uncertain whether this affects the incidence of symptoms. Further analysis depends on the basic epidemiology of thromboembolic symptoms. We therefore studied the pattern of such symptoms in a consecutive series of 1000 patients with primary TKR, with particular reference to risk factors and prophylaxis.

We reviewed all the clinical records and contacted all the patients individually, noting risk factors, prophylaxis, symptomatic pulmonary embolus (PE) or DVT and its timing, death and its causes, and all complications. All the patients wore antiembolism stockings, 83% had regional anaesthesia and 33.9% had chemical prophylaxis.

One patient died from PE on the day of surgery, having had no prophylaxis giving a rate of 0.1% (95% CI 0.003% to 0.56%). Symptomatic, radiologically confirmed thromboembolism (VTE) was common with a rate of 10.6% (95% CI 8.7% to 12.5%). There was a similar incidence of VTE in those with and without chemical prophylaxis (10.1% v 10.5%, RR 0.96, NS). VTE was more common in patients with risk factors (15.1% v 9.5%, RR 1.59, p = 0.02) and tended to occur earlier in this group (median day of onset 5 v 7, p = 0.01). Chemical prophylaxis did not reduce the frequency of symptomatic thromboembolism in either those with risk factors (RR 0.81, p = 0.5) or those without them (RR 0.94, p = 0.8). Haematoma or wound dehiscence was more common in those having chemical prophylaxis (11.9% v 6.9%; RR 1.73 95% CI 1.16 to 2.60). Readmission for symptomatic, radio-logically confirmed thromboembolism involved 1.1% of patients (95% CI 0.55% to 2.1%). Four patients were readmitted with proven non-fatal PE and six with proven DVT (the latest on day 40).

Our results show that the main risk factor for thromboembolism was TKR itself; chemical prophylaxis did not reduce the incidence of symptomatic thromboembolism but gave an increased perception of side-effects. New prophylactic methods or combinations of methods are needed, with their efficacy compared by randomised controlled studies of both the clinical and the radiological effect.

Aims

We investigated the efficacy and safety profile of commonly used venous thromboembolism (VTE) prophylaxis agents following hip and knee arthroplasty.

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.

We performed a meta-analysis of modern total joint replacement (TJR) to determine the post-operative mortality and the cause of death using different thromboprophylactic regimens as follows: 1) no routine chemothromboprophylaxis (NRC); 2) Potent anticoagulation (PA) (unfractionated or low-molecular-weight heparin, ximelagatran, fondaparinux or rivaroxaban); 3) Potent anticoagulation combined (PAC) with regional anaesthesia and/or pneumatic compression devices (PCDs); 4) Warfarin (W); 5) Warfarin combined (WAC) with regional anaesthesia and/or PCD; and 6) Multimodal (MM) prophylaxis, including regional anaesthesia, PCDs and aspirin in low-risk patients. Cause of death was classified as autopsy proven, clinically certain or unknown. Deaths were grouped into cardiopulmonary excluding pulmonary embolism (PE), PE, bleeding-related, gastrointestinal, central nervous system, and others (miscellaneous). Meta-analysis based on fixed effects or random effects models was used for pooling incidence data.

In all, 70 studies were included (99 441 patients; 373 deaths). The mortality was lowest in the MM (0.2%) and WC (0.2%) groups. The most frequent cause of death was cardiopulmonary (47.9%), followed by PE (25.4%) and bleeding (8.9%). The proportion of deaths due to PE was not significantly affected by the thromboprophylaxis regimen (PA, 35.5%; PAC, 28%; MM, 23.2%; and NRC, 16.3%). Fatal bleeding was higher in groups relying on the use of anticoagulation (W, 33.8%; PA, 9.4%; PAC, 10.8%) but the differences were not statistically significant.

Our study demonstrated that the routine use of PA does not reduce the overall mortality or the proportion of deaths due to PE.

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.