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 arth