Tranexamic acid in traumatic brain injury: systematic review and meta-analysis trumps a large clinical trial?
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EDITORIAL
Tranexamic acid in traumatic brain injury: systematic review and meta‑analysis trumps a large clinical trial? Andrew I. R. Maas1* , Ewout W. Steyerberg2,3 and Giuseppe Citerio4 © 2020 Springer-Verlag GmbH Germany, part of Springer Nature
Tranexamic acid (TXA) is a cheap, old antifibrinolytic agent that has been extensively tested in several settings where bleeding is a concern, including trauma and surgery, with variable results. In severely injured patients, when administered within the first 3 h following injury, TXA reduces overall mortality and death due to bleeding. The evidence in acute traumatic brain injury (TBI) is uncertain. In this issue of Intensive Care Medicine, Al Lawati et al. [1] present a well conducted, state-of the art systematic review (SR) and meta-analysis on the efficacy and safety of tranexamic acid (TXA) in acute TBI. They included nine RCTs that enrolled 14,846 patients. No statistically significant differences were found between patients treated with TXA and placebo groups for mortality, long term outcome, hematoma expansion and risk of adverse events. This is a somewhat different conclusion than the trumpeted interpretation of the CRASH-3 trial collaborators on the results of their large pragmatic RCT on TXA in TBI [2]. Only small differences were reported in CRASH-3 between the TXA and placebo groups in the primary efficacy analysis. Emphasis was placed on a pre-specified sensitivity analysis that excluded the most severe patients. This secondary analysis showed a marginally significant reduction in number of head-injury related deaths (n = 40 in 7637 patients) between the TXA and placebo groups (RR 0.89; 95% CI 0.80–1.00). Their interpretation that “treatment within 3 h of injury reduces head-injury related death” was broadly picked up *Correspondence: [email protected] 1 Department of Neurosurgery, Antwerp University Hospital and University of Antwerp, Wilrijkstraat 10, 2650 Edegem, Belgium Full author information is available at the end of the article
by the media and many clinicians across the world have now included the early use of TXA in the treatment of TBI. Caution against this media hype was expressed in an editorial published in this journal [3]. Only an uncertain and small benefit of early administration of TXA was found in a recent RCT on the effect of out-of-hospital administration of TXA on 6-month functional outcome in 966 patients with moderate or severe TBI [4]. Al Lawati et al. [1] are careful in formulating their conclusions, stating only that results do not support strong directives, either for giving TXA, or against giving TXA. This diplomatic phrasing is likely induced by the impact of the CRASH-3 trial results on clinical practice. The evidence-based pyramid positions systematic reviews and meta-analysis at the top the pyramid (Fig. 1) and the findings of a SR and meta-analysis override those of a large clinical trial [5]. In this case, however, the overall effect sizes for all-cause mortality in the current meta-analysis and in CRASH-3 were very
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