Ultra-Early Tranexamic Acid of No Benefit for Subarachnoid Hemorrhage

By Marilynn Larkin

January 18, 2021

NEW YORK (Reuters Health) - In patients with subarachnoid hemorrhage due to a ruptured aneurysm, ultra-early, short-term tranexamic acid (TXA) did not improve clinical outcomes in a multicenter, randomized controlled trial.

"The use of TXA in patients who have endured a subarachnoid hemorrhage has been a matter of debate for decades," Dr. Rene Post of the University of Amsterdam told Reuters Health by email, "We could now convincingly demonstrate that TXA does not improve the clinical outcomes in these patients at six months' follow-up."

"What surprised us," he said, "was that we did not find a significant reduction in the occurrence of rebleedings between the treatment groups, whereas this was always said to be the main reason for its use."

"Our study showed that in half of the patients the aneurysm was secured within 14 hours," he noted. "This early aneurysm treatment shortens the time window in which a rebleeding can occur, and thus the time window in which TXA can be effective. Secondly, we know that half of the rebleeds occur within three hours. Yet, despite ultra-early initiation of TXA treatment, the reduction of rebleeds was apparently not soon enough in our study to prevent a considerable amount of rebleedings."

"A second conspicuous finding is that an excellent clinical outcome, defined as an mRS score of 0.2, as opposed to the primary outcome (mRS score 0.3), was significantly lower in the TXA group," he added. "So, one may surmise that treatment with TXA could even be harmful. TXA treatment should therefore not be advised and removed from (inter)national guidelines."

As reported in The Lancet, Dr. Post and colleagues randomly assigned 955 patients with subarachnoid hemorrhage (mean age, 58; about 68% women) to TXA or usual care.

TXA was started immediately after diagnosis: 1 g bolus, followed by continuous infusion of 1 g every 8 h, and stopped immediately before aneurysm treatment, or 24 h after the start of the medication, whichever came first.

The primary endpoint was clinical outcome at six months, assessed by the modified Rankin Scale: good (0-3) or poor (4-6).

In the intention-to-treat analysis, 60% of patients in the TXA group had a good outcome versus 64% of controls (treatment center-adjusted odds ratio 0.86).

Rebleeding occurred after randomization and before aneurysm treatment in 10% of TXA patients and 14% of controls (OR, 0.71). Other serious adverse events - e.g., hydrocephalus, delayed cerebral ischemia, complications of aneurysm treatment - were comparable between groups.

The authors state, "Despite weak evidence for a reduction in rebleeds in the tranexamic acid treatment group compared with the control group in our study, this did not result in improved clinical outcome."

Dr. Alejandro Rabinstein of Mayo Clinic in Rochester, Minnesota, author of a related editorial, commented by email to Reuters Health, "Many clinicians with experience in subarachnoid hemorrhage, including myself, had been using very brief courses of TXA for prevention of rebleeding - just 1-3 doses in most cases, given the impetus for early aneurysm treatment, which now should even be more emphasized."

"The results of this trial are therefore practice-changing for many of us," he said. "I do think future guidelines will change based on this trial."

"As to idea of a single dose in patients presenting very early to hospitals without capabilities for aneurysm treatment and whose treatment will consequently be delayed until after patient transfer, I think that such approach is not unreasonable," he added. "Yet, it is not supported by the results of this trial (and) I would be very surprised if a trial on a single dose of TXA were funded in the future."

SOURCE: https://bit.ly/3qoX40p The Lancet, online December 21, 2020.

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