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
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:
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% This analysis shows that the incidence of adverse surgical events
with rivaroxaban was similar to enoxaparin.
Using general practitioner records and hospital
notes and through direct telephone conversation with patients, we investigated
the accuracy of nine patient-reported complications gathered from
a self-completed questionnaire after elective joint replacement
surgery of the hip and knee. A total of 402 post-discharge complications
were reported after 8546 elective operations that were undertaken
within a three-year period. These were reported by 136 men and 240
women with a mean age of 71.8 years (34 to 93). A total of 319 reported
complications (79.4%; 95% confidence interval 75.4 to 83.3) were
confirmed to be correct. High rates of correct reporting were demonstrated
for infection (94.5%) and the need for further surgery (100%), whereas
the rates of reporting deep-vein thrombosis (DVT), pulmonary embolism,
myocardial infarction and stroke were lower (75% to 84.2%). Dislocation,
peri-prosthetic fractures and nerve palsy had modest rates of correct
reporting (36% to 57.1%). More patients who had knee surgery delivered
incorrect reports of dislocation (p = 0.001) and DVT (p = 0.013). Despite these variations, it appears that post-operative complications
may form part of a larger patient-reported outcome programme after
elective joint replacement surgery.
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 ( Apixaban 2.5 mg twice daily is more effective than enoxaparin
40 mg once daily without increased bleeding.
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.
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.
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.
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
Patients who have undergone total hip or knee replacement (THR and TKR, respectively) are at high risk of venous thromboembolism. We aimed to determine the time courses of both the incidence of venous thromboembolism and effective prophylaxis. Patients with elective primary THR and TKR were enrolled in the multi-national Global Orthopaedic Registry. Data on the incidence of venous thromboembolism and prophylaxis were collected from 6639 THR and 8326 TKR patients. The cumulative incidence of venous thromboembolism within three months of surgery was 1.7% in the THR and 2.3% in the TKR patients. The mean times to venous thromboembolism were 21.5 days ( The risk of venous thromboembolism extends beyond the usual period of hospitalisation, while the duration of prophylaxis is often shorter than this. Practices should be re-assessed to ensure that patients receive appropriate durations of prophylaxis.
