Acute Cerebrovascular Conditions · Coagulopathy and Bleeding · Intracerebral Haemorrhage · Pharmacology · Subarachnoid Haemorrhage

TICH-2: No Benefit From TXA in ICH. What Now?

Tranexamic acid (TXA) has been held as something of a wonder drug. It’s cheap, largely demonstrated to be safe and has been given a role in a number of settings. The 2013 CRASH-2 trial showed improved survival in trauma with bleeding, and thus became one of the most widely cited publications in traumatology and emergency medicine. Several other studies of TXA in a number of haemorrhagic conditions have shown promising results, and at least one large multicentre trial is ongoing. The WOMAN trial, published in 2017, demonstrated a favourable effect on mortality in postpartum bleeding. A relatively small, but well-wrought trial by a Swedish group indicated improved outcomes in subarachnoid haemorrhage. CRASH-3 investigators are in the process of enrolling patients to evaluate the effect of TXA in traumatic intracranial bleeding.

With all that in mind, hopes have been high that TXA would also have a beneficial effect on patient-important outcomes in spontaneous intracerebral haemorrhage (ICH). In 2013 Sprigg and colleagues published the Tranexamic acid for hyperacute primary IntraCerebral Haemorrhage (TICH) trial. Her group enrolled a small number of patients in a feasibility study, demonstrating that TXA seemed safe to administer to ICH patients.

The purpose of the subsequent TICH-2 study was to evaluate the efficacy of the drug in a randomised placebo-controlled prospective trial. Published fairly recently in the Lancet, the study failed to show that TXA was superior to placebo for the primary outcome (90 day functional status).

“In this trial of tranexamic acid versus placebo after acute intracerebral haemorrhage, there was no significant difference between the groups in the primary outcome of functional status at day 90. However, in the tranexamic acid group, we detected significant reductions in the prespecified secondary outcomes of early death, haematoma expansion, and serious adverse events, consistent with tranexamic acid having an antifibrinolytic effect after intracerebral haemorrhage.”

In conclusion, the evidence is still insufficient to recommend empirical administration of TXA for ICH. However, the safety profile of the drug (e.g. no increased incidence of thromboembolism) is such that this should not deter from attempting to identify subgroups of patients who might benefit from anti-fibrinolytic treatment. While several smaller TXA-trials for ICH are ongoing, settling these issues would ultimately require a much larger RCT. For more insight, please also take a look at this recent commentary in the Lancet.

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