CRASH-3: a win for patients with traumatic brain injury

Clinical assessment of the antifibrinolytic drug tranexamic acid to reduce TBI-associated mortality is logical, particularly in view of the mortality reductions observed with tranexamic acid use in polytrauma patients without TBI12 and in women with post-partum haemorrhage.13 In The Lancet, the CRASH-3 trial collaborators14 report the results of a randomised, placebo-controlled trial of 12 737 adults with TBI (mean age 41·7 years [SD 19·0]; 80% men, 20% women). The use of 28-day head injury-related mortality as the primary endpoint probably biased the treatment effect towards the null because tranexamic acid is most likely to benefit patients with TBI with intracranial bleeding at risk of early mortality, whereas late deaths are unlikely to be affected by tranexamic acid. Future studies of tranexamic acid or other haemostatic interventions should reflect what is physiologically plausible and focus on endpoints of early bleeding-related death that clearly link intervention to outcome. vm/Getty Images In the CRASH-3 trial, tranexamic acid appears to be safe in patients with TBI, but as acknowledged by the authors, a clot-stabilising intervention such as tranexamic acid might cause an increase in risk of venous thromboembolism that was not captured in the study.