Source: CRASH-2 trial collaborators, 2010. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomized, placebo-controlled trial. Lancet. 2010 Jul 3;376(9734):23-32.
Efficacy Endpoints: All-cause mortality and bleeding-related mortality
Harm Endpoints: Vascular occlusive events, requirement for transfusion of blood products
Narrative: Injuries, particularly associated with motor vehicle accidents, represent a substantial cause of premature death worldwide. Approximately one-third of in hospital deaths due to trauma are directly attributed to haemorrhage. In addition, multi-organ failure can also be partially attributed to blood loss and its sequelae. To date, studies have been carried out examining the role of anti-fibrinolytic agents in elective surgery, however little research has been carried out examining the role of these drugs in trauma.
Benefits: This trial enrolled 20211 adult trauma patients from 274 hospitals across 40 countries. The trial showed that early intervention with a standardized regimen of tranexamic acid administered intravenously can significantly reduce all cause mortality as well as mortality due to bleeding.
Harms: No increase in rates of vascular occlusive events were noted, the adverse event of most concern related to administration of this drug.
Caveats: One caveat concerns internal validity. Given the drug’s reported mechanism of action, there are inconsistent findings. There was no difference between treatment and placebo groups in the rates of vascular occlusive events. While it is reassuring that a large systematic review of anti-fibrinolytic agents in surgery1 corroborates these safety findings for tranexamic acid, the authors note that observational studies of a similar agent, aprotinin, revealed increases in thrombotic events after early trials had reported no difference. Along the same lines, while it was expected that transfusion rates should decrease in patients treated with tranexamic acid, there was no significant difference between groups. However transfusion decisions are subjective and mortality was higher in the control arm, potentially reducing the opportunities for transfusion in that group.
For external validity, the study sample was a sick trauma cohort. Enrollment was limited to those with signs of significant hemorrhage or for those in whom a high suspicion of hemorrhage existed. Accordingly, about a third of the patients were in shock on presentation, systolic BP < 90 mm Hg, and about a third had a GCS between 3 and 8. This is consistent with the high mortality (1 in 6 dead at 1 month). The NNT cited above may be be significantly higher (less benefit) in a lower risk population. Second, many of the recruiting centres lacked sophisticated trauma systems that are well resourced with imaging and high tech surgical care. It is possible that the benefits of this drug would be lost in a more modern context.
Still, the drug is inexpensive and, based on this data, demonstrated no associated adverse effects, so its use should be considered in trauma patients with hemorrhagic shock or at high risk for bleeding.
Author: Kyle McCoy
Published/Updated: March 11, 2011
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