Detailed results from three randomised controlled trials (RCTs) evaluating middle meningeal artery (MMA) embolisation in the treatment of chronic subdural haematoma (cSDH) have been published in the New England Journal of Medicine (NEJM). With key initial data from each having been presented at the 2024 International Stroke Conference (ISC; 7–9 February, Phoenix, USA), EMBOLISE, STEM and MAGIC-MT were made available in NEJM on 20 November.
“Already quite common in older adults, by 2030, chronic subdural haematomas are expected to be the most common cranial neurosurgical disease in the world,” said EMBOLISE study co-lead author Jason Davies (University at Buffalo, Buffalo, USA). “We are changing the way that we are treating this very common disease. We are changing subdural haematoma from being a disease that commonly requires multiple surgeries to a disease that can be better treated with a simple, minimally invasive procedure that produces better outcomes.”
“This trial provides evidence that adding MMA embolisation should be a new standard of care for one of the most common neurosurgical conditions we see,” added co-lead author Jared Knopman (Weill Cornell Medicine, New York City, USA).
Led by co-principal investigators Davies and Knopman, the trial followed 400 participants (average age, 72 years) at 39 community and academic hospitals with chronic/subacute SDH between December 2020 and August 2023. Some 197 of these patients were randomised to the treatment group to undergo embolisation plus surgery, and 203 were randomised to the control group to receive surgery only. The treatment group saw patients undergo MMA embolisation using the endovascularly administered Onyx liquid embolic agent (Medtronic).
“For the last century, doctors have treated symptomatic subdural haematomas the same way; with surgery to create a small hole in the skull [burr-hole procedure] or removing a small section of skull to drain the blood [craniotomy],” Knopman commented.
“Right now, the problem is that—in up to 20% of these patients who require surgery—the haematoma will come back, so they have to undergo another craniotomy,” Davies added, outlining the need for a more effective and less invasive solution in cSDH treatment. “Every time they go back to the OR [operating room], it’s going to cause that patient more pain and suffering. It’s no fun to have to get a hole in the head. It increases the risk of infection, and contributes to an increase in morbidity and mortality, in addition to higher healthcare costs. So, we really want to reduce the number of times they go back to the OR.”
EMBOLISE’s final results revealed that cSDH patients in the treatment group ultimately achieved a dramatic, threefold reduction in repeat operations as compared to those in the control group. Haematoma recurrence or progression leading to another surgery within 90 days of the initial surgery occurred at a rate of approximately 4% in the treatment group compared to 11.3% in the control group. In addition, serious adverse events attributed to the MMA embolisation procedure occurred in 2% of patients who received it.
“The problem we wanted to address was whether or not we could change the way we treat this disease that’s very common in the elderly,” Davies noted. “Our study found a threefold reduction in the rates of recurrence. So, for every hundred patients who undergo treatment for this disease, we’ve reduced the number of recurrences from about 11 to about four.”
“In addition to demonstrating the role that the middle meningeal artery plays in the formation and recurrence of subdural haematomas, we have discovered an entirely new facet about the brain that has gone unknown and untreated for decades,” Knopman stated.
According to investigators, the next phase in the EMBOLISE trial involves patients who do not require surgery initially, and it will assess whether ‘up-front’ MMA embolisation can lead to patients—for example, those with larger cSDHs—avoiding the need for surgery in the first place.
“If we embolise these patients early, we may decrease the number who need to be taken to surgery later,” Knopman added.
STEM, another of the RCTs published in NEJM earlier this week, has shown that adjunctive MMA embolisation resulted in a lower risk of treatment failure compared to standard treatment alone—including surgical or medical management—without resulting in an increased incidence of disabling stroke or death in the short term, in symptomatic cSDH patients.
“This pivotal trial provides critical information to guide how we are treating our cSDH patients,” said co-principal investigator David Fiorella (Stony Brook University Medical Center, Stony Brook, USA). “STEM results show that the addition of MMA embolisation to either surgical or medical management reduces the incidence of recurrence or additional procedures, which is critical for this largely geriatric patient population.”
The international, prospective, multicentre STEM trial enrolled 310 patients, and compared those who received MMA embolisation with the Squid liquid embolic agent (Balt) as an adjunct to standard surgical or medical management against those who did not. The addition of embolisation showed a significant reduction in treatment failures, with a rate of 36% in the standard management group compared to only 16% in the embolisation group. Furthermore, the embolisation procedures did not increase rates of major adverse events or deaths.
“Embolisation of the MMA has rapidly evolved towards becoming the standard of care for patients suffering with cSDH,” stated co-principal investigator Adam Arthur (University of Tennessee Health Sciences Center, Memphis, USA). “These data confirm that the paradigm shift we have been seeing in clinical practice over the last few years is the most appropriate approach for these patients and can reduce treatment failures with this challenging disease state.”
A recent press release from Balt reiterates the EMBOLISE investigators’ sentiments that cSDH is a common disease primarily affecting older adults, and notes that a 2015 Veterans Affairs (VA) study found a prevalence rate of 79.4 per 100,000 persons. The authors predicted that the incidence rate of cSDH in the USA across ageing VA and civilian populations will reach 121.4 and 17.4 cases per 100,000 persons, respectively, by 2030—at which time approximately 60,000 cases of cSDH will occur each year in the country.
“The publication of the STEM trial in the New England Journal of Medicine highlights the importance of this prospective trial for this patient population,” said Balt chief executive officer (CEO) Pascal Girin. “We are very proud to have sponsored the STEM study, and look forward to continuing to invest in clinical research to advance the care of neurovascular patients and to bring the innovative Balt portfolio of products to market.”
The third and final recently published NEJM study—MAGIC-MT—was an open-label, multicentre RCT involving 722 symptomatic non-acute SDH patients in China. Patients were assigned to undergo burr-hole drainage or receive non-surgical treatment at physician discretion, with patients in each group then randomly assigned 1:1 to undergo MMA embolisation using Onyx or to receive usual care. According to Ying Mao (Fudan University, Shanghai, China) and the other MAGIC-MT investigators, patients whose condition warranted craniotomy were excluded. Their primary endpoint was symptomatic recurrence or progression of the SDH within 90 days after randomisation, while secondary endpoints included clinical and imaging outcomes, and the main safety endpoint was any serious adverse event, including death.
Some 360 patients were assigned to the embolisation group and 362 to the usual-care group in MAGIC-MT. Burr-hole drainage was performed in 78.3% of the enrolled patients and, among the patients who underwent burr-hole drainage, the procedure occurred after embolisation 99.6% of the time. Symptomatic SDH recurrence or progression within 90 days occurred in 24 patients (6.7%) in the embolisation group and 36 (9.9%) in the usual-care group, resulting in a between-group difference of −3.3 percentage points (95% confidence interval [CI], −7.4–0.8; p=0.1). In addition, the incidence of serious adverse events was lower in the embolisation group than in the usual-care group (6.7% vs 11.6%; p=0.02).
“Among patients with symptomatic non-acute subdural haematoma—of whom 78% underwent burr-hole drainage—middle meningeal artery embolisation resulted in a 90-day incidence of symptomatic recurrence or progression, similar to that with usual care, but was associated with a lower incidence of serious adverse events,” Mao and colleagues conclude, writing in NEJM.
Alongside these three landmark RCTs, NEJM has also published an accompanying editorial authored by Peter Kan (University of Texas Medical Branch, Galveston, USA), which discusses the present role of MMA embolisation in cSDH treatment paradigms.
