Tranexamic acid linked to lower death rate in some brain injury patients

A large randomised controlled clinical trial has linked the early use of tranexamic acid to a small fall in the risk of death in a subgroup of traumatic brain injury (TBI) patients.

Tranexamic acid is an off-patent drug used in the management of bleeding trauma patients. Previous studies have shown the benefits of the drug in that population but there is a lack of evidence on its use in TBI patients.

To address the evidence gap, researchers enrolled 12,737 patients with TBI and randomised them to receive tranexamic acid or placebo. The trial began enrolling patients treated within eight hours of injury but cut the time window to three hours mid-study in response to external data suggesting that tranexamic acid is ineffective when treatment is delayed.

More than 70% of participants were treated within three hours of suffering a head injury. Among that group, 18.5% of subjects who received tranexamic acid died as a result of head injuries in the 28 days after treatment, compared to 19.8% in the placebo group.

The difference between the two groups fell short of statistical significance. However, the drug fared better in prespecified subgroup analysis.

Among patients with mild-to-moderate TBI, the death rates in the tranexamic acid and control arms were 5.8% and 7.5%. That difference is statistically significant.

“This hugely exciting new result shows that early treatment with [tranexamic acid] also cuts deaths from head injury. It’s an important breakthrough and the first neuroprotective drug for patients with head injury,” Ian Roberts, professor of clinical trials at the London School of Hygiene & Tropical Medicine, said in a statement. Roberts co-led the study, results from which were published in The Lancet.

Subgroup analyses can generate misleading results, falsely suggesting that a drug works. However, the Lancet study used prespecified subgroups selected on a pathophysiological rationale, suggesting the findings of the tranexamic acid trial may be more reliable than some subgroup analyses.

Even if the subgroups present an accurate picture of the effects of tranexamic acid, the extent of the risk reduction is small. However, given a 2018 study estimated 69 million people worldwide sustain a TBI every year, there is scope for small risk reductions to benefit significant numbers of people.

The case for using tranexamic acid is further strengthened by the lack of any downside to doing so. A course of treatment in the UK costs around £6.20 and, while some studies have linked the drug to an increase in thromboembolic events, the TBI study found no difference in the rates of complications in the treatment and placebo arms.