Aspirin versus enoxaparin for the initial prevention of venous thromboembolism following elective arthroplasty of the hip or knee: A systematic review and meta-analysis.

Aspirin is perceived to be non-inferior to enoxaparin, a low-molecular-weight heparin, for the prevention of venous thromboembolism (VTE) following elective arthroplasty of the hip or knee and is recommended in clinical guidelines internationally. Previous systematic reviews of aspirin as VTE prophylaxis have been limited by the inclusion of heterogenous studies where aspirin is commenced after the initial high-risk postoperative period. The purpose of this systematic review and meta-analysis was to compare the efficacy and associated harms of aspirin and enoxaparin when used as VTE prophylaxis in the initial postoperative period following elective arthroplasty of the hip or knee. We sought to: (1) to compare the use of aspirin versus enoxaparin following elective joint replacement of the hip or knee on the primary outcomes of incidence of VTE and mortality up to 3 months postoperatively and (2) assess the efficacy of aspirin with respect to secondary outcomes such as major or minor bleeding events. We hypothesised that aspirin would have equivalent efficacy for the prevention of VTE when used as initial prophylactic agent, without increasing harm from bleeding events. We searched Pubmed, Embase, Medline and Cochrane Central for randomized controlled trials reporting the primary outcomes of VTE incidence and mortality. Secondary outcomes included major (compromise of organ, limb or muscle function requiring unplanned re-operation) and minor bleeding events (wound ooze, minor bleed, infection). Included trials underwent a risk of bias and quality of evidence assessment using the GRADE criteria. Four trials involving 1507 participants who underwent elective lower limb arthroplasty were included. We did not detect a significant difference in overall VTE rates when comparing aspirin versus enoxaparin (RR, 0.84; 95% CI: 0.41 to 1.75; p=0.65). Mortality was reported by one study and no events were recorded. There were no significant differences in the rates of all major (RR, 0.84; 95% CI: 0.08 to 9.16) or minor (RR, 0.77; 95% CI: 0.34 to 1.72) bleeding events between the aspirin and enoxaparin groups. Included trials demonstrated a significant risk of bias, and Low to Very Low quality of evidence for primary outcomes, and Moderate to Very Low for secondary outcomes. There is currently a lack of high quality randomised controlled trials supporting the use of aspirin as VTE chemoprophylaxis in the initial postoperative period for both total hip and total knee arthroplasty. The results of this meta-analysis provide cautious endorsement for the position that aspirin is likely a safe alternative to enoxaparin for TKA patients as part of a multimodal enhanced recovery protocol, but care is advised for THA patients owing to a lack of data from trials. Current evidence from randomized controlled trials is generally of low quality, and does not estimate critical event data for VTE incidence or mortality, as well as major and minor bleeding events with sufficient certainty. PROSPERO Registration CRD42018110784. II, systematic review.

Farey JE ，An VVG ，Sidhu V ，Karunaratne S ，Harris IA ... -  《Orthopaedics & Traumatology-Surgery & Research》

Safety and effectiveness of aspirin and enoxaparin for venous thromboembolism prophylaxis after total hip and knee arthroplasty: a systematic review.

Patients undergoing total hip arthroplasty (THA) or total knee arthroplasty (TKA) are at risk of venous thromboembolism (VTE). Australian orthopaedic guidelines recommend aspirin and low-molecular-weight heparin (e.g. enoxaparin) for VTE prophylaxis; however, there is debate in the international literature around the use of aspirin as VTE prophylaxis. This review assesses the risks and benefits of aspirin compared to enoxaparin as VTE prophylaxis for patients undergoing THA or TKA. A systematic review was conducted to identify relevant randomized controlled trials. Studies comparing enoxaparin, aspirin and/or placebo for VTE prophylaxis in THA or TKA patients were included. Network meta-analysis (NMA) was performed to calculate risk ratios (RRs) and confidence intervals (CIs). Quality appraisal was conducted by assessing risk of bias and the strength of the evidence. Nine randomized controlled trials were eligible for inclusion. The NMA found no statistically significant differences for the investigated outcomes: total DVT rates (RR = 1.21, 95% CI 0.86, 1.72), symptomatic pulmonary embolism (PE) rates (RR = 1.02, 95% CI 0.02, 50.86), major haemorrhage (RR = 0.97, 95% CI 0.02, 50.99) and wound complication (RR = 0.73, 95% CI 0.17, 3.20). The occurrence of PE was rare. Due to limited data, sub-group analysis was not possible. The overall quality of evidence in the NMA is considered to be very low. This review did not find statistically significant differences between aspirin and enoxaparin. Future studies should identify more evidence, particularly for rare outcomes such as PE, as this might help decision-makers to get consensus on the use of aspirin as VTE prophylaxis.

Nadi S ，Vreugdenburg TD ，Atukorale Y ，Ma N ，Maddern G ，Rovers M ... -  《-》

Anticoagulants (extended duration) for prevention of venous thromboembolism following total hip or knee replacement or hip fracture repair.

Forster R ，Stewart M 《Cochrane Database of Systematic Reviews》

Clinical Effectiveness and Safety of Aspirin for Venous Thromboembolism Prophylaxis After Total Hip and Knee Replacement: A Systematic Review and Meta-analysis of Randomized Clinical Trials.

Matharu GS ，Kunutsor SK ，Judge A ，Blom AW ，Whitehouse MR ... -  《-》

Effect of Aspirin vs Enoxaparin on Symptomatic Venous Thromboembolism in Patients Undergoing Hip or Knee Arthroplasty: The CRISTAL Randomized Trial.

CRISTAL Study Group ，Sidhu VS ，Kelly TL ，Pratt N ，Graves SE ，Buchbinder R ，Adie S ，Cashman K ，Ackerman I ，Bastiras D ，Brighton R ，Burns AWR ，Chong BH ，Clavisi O ，Cripps M ，Dekkers M ，de Steiger R ，Dixon M ，Ellis A ，Griffith EC ，Hale D ，Hansen A ，Harris A ，Hau R ，Horsley M ，James D ，Khorshid O ，Kuo L ，Lewis P ，Lieu D ，Lorimer M ，MacDessi S ，McCombe P ，McDougall C ，Mulford J ，Naylor JM ，Page RS ，Radovanovic J ，Solomon M ，Sorial R ，Summersell P ，Tran P ，Walter WL ，Webb S ，Wilson C ，Wysocki D ，Harris IA ... -  《-》