New Data to Alter Planned ICH Guidelines

ABU DHABI, UAE — In the past 9 months, a surge of new trials related to the management of intracranial hemorrhage (ICH) has led the European Stroke Organisation (ESO) to delay issuing a planned guidelines update.
In a summary of a selection of these studies at the 16th World Stroke Congress (WSC) 2024, Thorsten Steiner, MD, PhD, professor of neurology, University of Heidelberg, Heidelberg, Germany, said that many simply reinforce prior evidence, but he identified several that will change recommendations when they are finally released.
One of these is the ENRICH trial, published in The New England Journal of Medicine earlier this year. The study evaluated devices (BrainPath and Myriad; NICO Corporation) used in minimally invasive surgery (MIS) to reduce hematoma volume by evacuating blood.
In ENRICH, 300 patients with an acute ICH and a hematoma volume between 30 and 80 mL were randomized within 24 hours of the onset of symptoms to device or no surgery. Both groups received guideline-recommended medical management.
The reduced hematoma volume in the surgery group was associated with a lower rate of mortality (9.3% vs 18.0%) and an improved functional outcome, according to Steiner, who led the last set of ESO intracerebral hemorrhage guidelines, issued in 2014.
When incorporated into a meta-analysis of other devices employed in MIS to reduce the hematoma volume, this approach will now be recommended in the next set of guidelines.
“A preliminary phrasing of the recommendation might be that MIS should be considered [for hematoma evacuation] to reduce mortality and improve functional outcomes,” Steiner said.
The SWITCH trial is another recently published study that is going to affect the upcoming ICH guidelines, according to Steiner. In SWITCH, which was stopped early due to a lack of funding, 201 patients with an acute ICH involving the basal ganglia or thalamus were randomized to craniotomy for decompression plus best medical therapy or best medical therapy alone.
Severe adverse events were not more common in the group randomized to craniotomy, but more of the craniotomy patients had a favorable outcome on the primary endpoint of a modified Rankin scale of 5-6 at 180 days, whether evaluated on intention-to-treat (44% vs 58%) or per protocol (47% vs 60%) analysis.
“The preliminary wording of the recommendation is to consider use of decompression craniotomy in selected patients” with deep severe ICH, Steiner said. However, he also anticipates the new guideline to emphasize that craniotomy “should be an interdisciplinary decision” as well as one that involves families and, when possible, patients.
There were also several studies that supported the principle of hematoma reduction in ICH, including the ANNEXA-1 trial and the INTERACT-4 trial.
In ANNEXA-1, 263 patients who had taken a factor Xa inhibitor within 15 hours on an ICH were randomized to receive the factor Xa reversal agent andexanet alfa or usual care. Nearly 90% of patients had a history of atrial fibrillation.
While the primary endpoint was a composite of hematoma volume expansion and a National Institutes of Health Stroke Scale score < 7, the main benefit was driven by hematoma volume reduction, according to Steiner. The reversal agent was accompanied by an increased risk for thrombotic events that did not outweigh a favorable benefit-to-risk ratio. Rather, Steiner suggested the trial adds to the growing evidence that early control of hematoma expansion should be a therapeutic goal in ICH.
The INTERACT4 trial was another such trial supporting the same message. Conducted in China, this study tested the value of initiating control of hypertension in patients with suspected stroke even before reaching the hospital when the type of stroke has not yet been established with imaging. The overall study result was negative, but those with an ICH did have an improved outcome, according to Steiner.
“This was the first trial to show a reduction in the hematoma expansion by early blood pressure control leads to an improved outcome,” Steiner said. Even if this benefit was observed only in a subgroup, he expects this to influence the coming guidelines.
Upcoming results from another randomized study, STOP-MSU, were also involved in the decision to withhold release of the updated ICH guidelines. The question posed by this study was whether initiating tranexamic acid (TA) within 2 hours of an ICH would attenuate hematoma growth relative to a later start.
Ultimately, the study results were neutral in that early TA did not significantly attenuate hematoma size or improve functional outcomes. Despite the fact that STOP-MSU did not support early TA in ICH, Steiner said it would not affect a recommendation to consider routine use of TA on the basis of other positive trials.
Except for the STOP-MSU study, one recurring message from the ICH trials published in 2024 is that intervening quickly almost always reduces risk, Steiner said.
“One signal you see again and again in ICH studies is that the earlier you treat, the better the outcome,” he said.
Santiago Ortega-Gutiérrez, MD, the principal investigator at the Cerebrovascular & Neurointerventional Lab at the University of Iowa, Iowa City, Iowa, underscored this principle.
Participating in the same WSC session devoted to guidelines, Ortega-Gutiérrez reviewed the 2023 American Heart Association/American Stroke Association guidelines for aneurysmal subarachnoid hemorrhage. But it was in the panel discussion that followed that he repeated an old adage.
“Time is brain,” he said, indicating that new methods of delivering effective treatments should be kept in mind for ICH as well as for ischemic stroke. He noted that the delay in the release of the updated ICH guidelines from the ESO allows for new data to provide additional emphasis on this message.
Steiner reported financial relationships with AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, and Pfizer. Ortega-Gutiérrez reported financial relationships with Medtronic, Siemens, and Stryker.
 
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