Compared with placebo, tranexamic acid did not reduce hematoma growth in patients with intracerebral hemorrhage (ICH), a new study shows.
In the randomized controlled trial, the rate of hematoma expansion was 40.4% among patients who received tranexamic acid and 41.5% among those who received placebo. The degree of disability at 90 days also did not differ between treatment arms.
“Our work has once again shown that tranexamic acid is safe in spontaneous ICH,” Jingyi Liu, MD, a physician in the neurocritical care unit at Beijing Tiantan Hospital, Capital Medical University, Beijing, China, told Medscape Medical News. “Larger studies with more specified population are needed to further assess safety and efficacy of tranexamic acid in patients with ICH.”
The findings were presented at the European Stroke Organization Conference (ESOC) 2021, which was held online. They were also published online June 28 in Stroke and Vascular Neurology.
Imaging-Based Patient Selection
ICH is often fatal and entails a high risk for disability, the researchers write. Approximately 40% of patients with ICH die within a month of onset, and about two thirds of patients do not achieve long-term functional independence.
Intracerebral hematoma expansion is predictive of poor clinical outcome in ICH. Data indicate that tranexamic acid, an antifibrinolytic agent, reduces hematoma expansion. But evidence of a clinical benefit of tranexamic acid has been elusive, they note.
This lack of observed benefit may result from the inappropriate selection of research participants. The emergence of imaging biomarkers may help address this potential problem. In recent years, the blend sign and the black hole sign on noncontrast CT, as well as the spot sign on CT angiography, have been associated with higher risk for hematoma expansion and worse clinical outcome, the researchers write.
Between January 2015 and March 2020, the investigators enrolled consecutive patients with acute primary spontaneous ICH into their prospective study. Eligible patients presented at any of 10 stroke centers in China. They had the spot sign, blend sign, or black hole sign at admission and were able to receive treatment within 8 hours of onset.
The investigators randomly assigned patients in equal groups to receive placebo (0.9% NaCl) or tranexamic acid. Patients and study investigators were blinded to treatment assignment. Treatment was administered as an intravenous infusion over 8 hours.
The study’s primary endpoint was intracerebral hematoma expansion by 24 hours after start of treatment. Expansion was defined as an increase of >6 mL or a growth of >33% from baseline. Secondary endpoints included poor clinical outcome, defined as a Modified Rankin Scale (mRS) score of 4 to 6, and all-cause mortality, both at 90 days.
No Differences in Disability
The investigators enrolled 171 patients in their study; 24-hour CT images were available for 169 of them. Follow-up data at 90 days were available for 164 patients.
The mean age of the patients was 55.9 years, and 72.5% of participants were men. At baseline, the mean ICH volume was 23.7 mL, and the median hematoma volume was 19.8 mL.
All patients received treatment within 8 hours. Hematoma expansion occurred in 40.9% of patients overall; 34.9% had a poor clinical outcome.
The investigators found no significant difference between treatment arms in the rate of hematoma expansion. This outcome occurred in 40.4% of the tranexamic acid group and 41.5% of the placebo group (odds ratio, 0.96; P = .89).
In addition, the researchers found no significant difference in the distribution of mRS scores at day 90 (P = .70). The rate of all-cause mortality at 90 days was lower in the tranexamic acid group (8.1%) than in the control group (10.0%), but this difference was not statistically significant (P = .71).
Potential Clotting Risk
One reason for the lack of observed benefit with tranexamic acid may be an inappropriate sample size, said Liu. Patient recruitment was difficult, especially in centers that used the spot sign as an inclusion criterion.
“We think a positive result could be seen in a substantially larger sample size,” said Liu. “Furthermore, we infer from our subgroup analysis that a more specified patient selection and shorter treatment window may be required for better effect.”
In some of their subgroup analyses, the researchers found a trend toward an increased effect in patients with moderate-size hematoma who received treatment in an earlier window. “That could be the targeted population for future studies,” said Liu. “We are working on further analysis of the population and possibly international collaboration.”
But tranexamic acid also entails risks, said Louis R. Caplan, MD, professor of neurology at Harvard Medical School, Boston, Massachusetts, who commented on the findings for Medscape Medical News. “Tranexamic acid works on the thrombolytic system, so it increases clotting, and it does have a risk in people who are older and have risk factors for coronary disease and pulmonary embolism.”
As in ischemic stroke, time to treatment is a crucial consideration. Patients with ICH may receive treatment within 5 or 6 hours of onset, but most hemorrhages have reached their maximum size at that point. “The number of people that you can actually help by reducing the size is small,” said Caplan. “And then reducing the size in most hemorrhages doesn’t make any clinical difference.”
Stereotactic drainage, in which fluid is physically removed, is more likely to lead to long-term improvement for some patients with hemorrhage than limiting expansion, said Caplan. “That seems to be a more promising therapy,” he added.
The study was supported by the National Key R&D program of China, the National Natural Science Foundation of China, the National Natural Science Foundation of China, the National Natural Science Foundation of China, and the Beijing Science and Technology Commission. Liu and Caplan have disclosed no relevant financial relationshps.
European Stroke Organisation Conference (ESOC) 2021: Presented September 1, 2021.
Stroke Vasc Neurol. Published online June 28, 2021. Full text
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