Tranexamic Acid in Total Knee Arthroplasty: Mixed Treatment Comparisons and Recursive Cumulative Meta-Analysis of Randomized, Controlled Trials and Cohort Studies

Tranexamic acid (TXA) has been shown to be effective in patients with total knee arthroplasty (TKA) in clinical studies with no consensus with regard to the most appropriate route of administration. We conducted a network meta-analysis to compare the evidence available on efficacy and safety of TXA in TKA. Electronic databases were searched for randomized, clinical trials and cohort studies that evaluated TXA in TKA. Publication bias, risk of bias and inconsistencies were assessed. Direct and indirect comparisons were carried out for blood transfusion rate and incidence of thrombotic complications. Sensitivity analyses and grading of evidence were performed for key comparisons. A cumulative meta-analysis was conducted for comparisons that had a minimum of 10 included studies. A total of 19 studies with 8916 participants were pooled for this network meta-analysis. No inconsistencies and publication bias were observed. Low risk of bias was observed for the majority of the included studies. When compared to placebo, the pooled estimates for mixed treatment analyses favoured (in the order of higher ranking) the combined pre-operative oral and topical TXA, intra-operative intravenous TXA with topical TXA, pre-operative intravenous TXA, intra-operative and post-operative intravenous TXA, intra-operative intravenous bolus and topical TXA. Additionally, combined intravenous and topical TXA performed better than topical TXA alone. No significant changes were observed in the sensitivity analyses. No significant differences were observed in the risk of thrombotic complications between the interventions. TXA is efficacious and safe in patients with TKA. The combined topical and intra-operative intravenous TXA may perform better.