麻豆传媒

PHOENIX -- For chronic or subacute subdural hematoma, embolization of the middle meningeal artery (MMA) reduced recurrence, three randomized trials showed.

Two trials with the Onyx liquid embolic system and one with the Squid liquid embolic system were reported with what one presenter called "very consistent" findings at the closing late-breaking science session of the American Stroke Association International Stroke Conference.

The approach has been used sporadically off-label for subdural hematoma, although familiar to neurointerventionalists due to use in dural arteriovenous fistulas and arteriovenous malformation, noted session co-moderator Tudor G. Jovin, MD, of the Cooper Neurological Institute in Camden, New Jersey.

"This is big news, these three trials, because they are establishing this procedure as a standard of care," he told 麻豆传媒. "Level one evidence was lacking, and I think this will change practice and change guidelines."

"I would draw the analogy with the thrombectomy trials of 2015. There were some centers that were doing it, but it wasn't the standard of care," he said. "It's going to be as impactful as the 2015 trials have been for thrombectomy."

Surgical treatment with craniotomy or by drilling a burr hole to drain the hematoma appears to have been in use for thousands of years, based on . Conservative medical management with treatments like tranexamic acid administration, steroids, or statins is common as well.

However, post-surgical recurrence rates are up to 20% in many series. A recent showed a 36% nonsuccess rate for conservative therapy.

"As that fluid has accumulated on the surface of the brain, you tend to develop membranes," noted Jason Davies, MD, PhD, of the State University of New York at Buffalo. "You have inflammatory cells that come in that have a pro-angiogenic role. You start to get ingrowth of neovascularity from the overlying dura, and those vessels tend to be relatively poorly formed and to be leaky. And so what happens is that these membranes start having repeated microhemorrhages, fluid exudates, and they really take on a life of their own."

"So the thought is, if we can devascularize these membranes by interrupting the blood vessels, we can dry up the membranes, interrupt that cycle, and hopefully reduce the recurrence rates and improve clinical outcomes for the patient," he explained.

Onyx Results

Davies reported interim results from the EMBOLISE trial cohort undergoing surgical management. The trial -- designed to support an application to the FDA for an expanded indication -- also has an arm that randomized patients who elected conservative management without surgery; that data will be reported at a later date.

In the surgical cohort, subdural hematoma recurrence or progression requiring surgical drainage through 90 days occurred in 4.1% of patients randomized to embolization with the Onyx liquid embolization system, compared with 11.3% treated with surgery alone (RR 0.36, 95% CI 0.11-0.80, P=0.0081).

The number needed to treat was about 14, or just 12 in a modified intent-to-treat analysis excluding patients treated outside the protocol.

Deterioration in neurologic function was similar between groups (11.9% and 9.8%, respectively, P=0.0022 for non-inferiority).

The surgical cohort in the trial included 400 patients at 60 centers across the U.S. Inclusion criteria required a premorbid modified Rankin Score (mRS) of 0-3, diagnosis of subacute or chronic subdural hematoma on MRI or CT imaging with corroborating clinical symptoms, and characteristics that ruled out observation alone. Radial access and local anesthesia were encouraged for the procedure.

All embolization procedures achieved technical success for the target vessel, with 1.1% reflux to non-target vessels. Serious adverse events (AEs) related to the embolization procedure occurred in 2% of patients within 30 days, but none of the four cases were deemed related to Onyx.

Neurologic death in the first 90 days were more than twice as common in the embolization group (4.6% vs 2.0%), but almost all were due to the subdural hematoma without any related to Onyx or the embolization procedure. No ipsilateral visual complications or serious intracerebral hemorrhage related to Onyx or the embolization procedure occurred either.

One limitation was about 10% of missed clinic visits at 90-day follow-up given the timing of the trial around the COVID-19 pandemic (December 2020 to August 2023) with a fairly frail, elderly population. The average age was around 71 in the study.

"We believe MMA embolization should be considered as an adjunct for patients who undergo surgical drainage of chronic or subacute subdural hematomas," concluded co-presenter Jared Knopman, MD, of Weill Cornell Medicine in New York City. "We're very excited by these results."

MAGIC-MT

A second trial from China, MAGIC-MT, also showed a 4.93-percentage point reduction in symptomatic recurrence or progression of subdural hematoma or death within 90 days after randomization to MMA embolization using Onyx compared with locally determined care management alone (7.2% vs 12.2%, P=0.02).

Ying Mao, MD, PhD, of Huashan Hospital and Fudan University in Shanghai, reported that the trial included 727 symptomatic non-acute subdural hematoma patients with a shift in midline structure or deformation of local cerebral cortex. It had inclusion criteria similar to the EMBOLIZE trial, Mao noted. It likewise allowed local doctors to decide on conservative management or burr hole drainage, however both groups were randomized into the same trial cohort, unlike EMBOLIZE.

Symptomatic subdural hematoma recurrence (maximum thickness >10 mm) or re-operation within 90 days was numerically less common with embolization in the 78% of patients who underwent burr-hole drainage (4.7% vs 5.2%).

For those managed conservatively, symptomatic subdural hematoma progression showed a larger impact of embolization, with rates of 1.7% versus 4.7%. Other factors associated with a larger treatment effect were known head trauma, smaller midline shift, and smaller hematoma volume.

Safety findings actually showed significantly fewer serious AEs within 90 days in the embolization group (6.7% vs 11.6%, P=0.02). Embolization-related complications occurred in 0.8% of patients, with one case of facial nerve paralysis and two of contrast agent allergy.

SQUID Results

A novel liquid embolization system, dubbed Squid, more than tripled the likelihood of treatment success compared with standard management, reported Adam Arthur, MD, of Semmes-Murphey Neurological Clinic in Memphis, Tennessee, who called the results "very consistent" with what had already been presented at the late-breaking science session.

Embolization with Squid yielded a 15.5% failure rate within 180 days compared with 39.2% using standard management alone (OR 3.60, 95% CI 1.91-6.78) when failure was defined three ways: residual or re-accumulation to at least a 10-mm thick hematoma, re-operation or surgical rescue, or any new major event (disabling stroke, myocardial infarction, or death from any neurological cause).

Notably, patients who had MMA embolization along with conservative management actually had a lower risk of treatment failure than those who got surgery alone (19.1% vs 25.4%). The lowest risk was seen in those who got the combined surgery-plus-embolization strategy (12.3%), whereas fully 59.2% had failure with non-surgical management alone.

The STEM pivotal trial randomized 310 patients (stratified by surgical management, which 189 elected, or non-surgical care).

Participants were ages 30 and older and had premorbid mRS 0-1 in the prior 12 months. Their chronic subdural hematoma needed to be symptomatic and measure at least 10 mm at its thickest point and exert local cortical flattening or midline shift.

No deaths in the trial were attributed to the procedure or device, and 30-day all-cause mortality was similar between treatment arms. The only major disabling stroke occurred in the control group.

Of the other endpoints for which data will be reported later, Arthur noted that mRS shift, hospital length of stay, and neurocognitive scores will be of particular interest.

"Again, we're looking at an older patient population and trying to help them to maintain independence and maintain cognitive competence later in life," he concluded.