A new study from Japan has become the first randomised controlled trial (RCT) to demonstrate the effectiveness of endovascular mechanical thrombectomy procedures in patients who have severe strokes involving clots in one or more large brain arteries. This preliminary, late-breaking research, which was presented at the International Stroke Conference (ISC 2022; 9–11 February, New Orleans, USA), found that patients who suffer a severe ischaemic stroke may regain far more function if their clots are mechanically removed in addition to standard medical therapy. An increased occurrence of intracranial haemorrhage was, however, also observed in patients who underwent a thrombectomy in the study.
“Our findings confirm that anyone who suffers from stroke should be transferred to a medical facility capable of endovascular therapy as soon as possible,” said senior author of the study Takeshi Morimoto (Hyogo College of Medicine, Nishinomiya, Japan)—who also presented these data at ISC 2022. “The benefit of endovascular therapy is not limited by the severity or region of a stroke. These patients may have the chance to more fully recover from stroke and go back to their previous lives and activity levels.”
In 2018, the American Heart Association (AHA) updated its stroke treatment guidelines to recommend endovascular therapy—which involves clot removal via mechanical thrombectomy—for select stroke patients, with a view to improving their odds of functional recovery. As per an AHA press release, effectiveness of the approach had previously been established for patients whose large-vessel clots disrupted blood flow to fewer areas of the brain. However, clinical experience was mixed for patients with more severe strokes whereby a clot interrupts blood flow to a large area of the brain.
“I have often encountered a dramatic improvement in a patient just after the mechanical clot removal procedure, even when the infarction area was large,” said Shinichi Yoshimura (Hyogo College of Medicine, Nishinomiya, Japan), lead author of the study. “Yet, patients sometimes also experienced severe haemorrhagic transformation [a life-threatening complication that occurs when blood from outside the brain crosses the blood-brain barrier and worsens stroke outcome] after the artery was reopened. So, in Japan, our stroke physicians are always cautious about endovascular therapy when the infarction area is large.”
In this randomised study, which has now also been published in the New England Journal of Medicine, 203 stroke patients (average age of 76 years; 44% women) were treated at 45 hospitals in Japan. Most of these patients (71%) were examined and had magnetic resonance imaging (MRI) or a computed tomography (CT) scan of the brain within six hours after stroke symptoms were first noticed—the timeframe that patients are generally considered eligible for endovascular therapy. The other patients were seen between six and 24 hours after symptoms were noticed, and additional imaging showed areas of the brain that might benefit from prompt treatment.
On imaging, all patients were found to have clots blocking a large artery in the brain—either the internal carotid artery, the proximal middle cerebral artery, or both. The strokes were rated as severe (median score of 22 on the National Institutes of Health Stroke Scale [NIHSS], which assesses a patient’s ability to perform normal functions such as speaking and moving) and involved disrupted blood flow to large areas of the brain (about seven out of 10 regions).
After imaging, the patients were randomly selected to receive either standard medical care for stroke—consisting of providing intravenous fluids, controlling blood pressure and other risk factors, and administering clot-busting medications for select patients at lower risk of bleeding—or standard medical care plus endovascular therapy performed within an hour after imaging. Due to bleeding concerns, intravenous clot-busting medications were sparingly administered to select patients in a similar proportion in both treatment groups (27 of those who received endovascular therapy and 29 who received standard care).
Comparing the 100 patients who received endovascular therapy plus standard care with 102 on standard therapy alone, the analysis found:
- Patients who received endovascular therapy were 2.43 times more likely (31% vs. 13%) to be able to walk without assistance and to have a residual disability rated as none to moderate 90 days later.
- After 90 days, more of the patients (14% vs. 6.9%) who received endovascular therapy were considered functionally independent, meaning they were either able to carry out all their pre-stroke activities or to have a slight disability that did not require daily assistance.
- At 48 hours after treatment, more of the patients (31% vs. 8.8%) who received endovascular therapy had major early neurological improvement (improved ability to talk and move limbs).
In addition, several outcomes were compared to evaluate the safety of adding endovascular therapy to medical treatment, with researchers reporting:
- Within 48 hours, scans revealed that more of the patients who received endovascular therapy had experienced some bleeding within the brain (with or without symptoms), 58% vs. 31%, respectively.
- However, the number of patients who experienced other adverse outcomes was similar in the two treatment groups. The adverse events included brain bleeding within 48 hours that caused a worsening of neurological status (four points or greater worsening on the NIHSS); the need for surgery to relieve pressure on the brain in the first week; death within 90 days; or the recurrence of ischaemic stroke within 90 days.
“The finding of more intracranial bleeding in the patients who received endovascular therapy is very important,” Morimoto added. “However, there were haemorrhages with symptoms and some that caused no symptoms. The haemorrhages with no symptoms were detected on imaging conducted for this study in the endovascular treatment group, not in the standard practice group. Symptomatic intracranial haemorrhage still occurred more commonly among patients in the endovascular group, however, it was not a statistically significant difference from the standard care group.”
The results of this study may not be generalisable to the USA or western countries—because it was conducted in Japan, where there is less use of intravenous thrombolysis than in the USA and other western countries, and where more strokes are imaged with MRI compared to CT, perhaps leading to different estimates of how many brain regions are affected by the stroke, the AHA release states. Due to these differences in treatment protocols, this study’s results may over- or underestimate the effectiveness of endovascular therapy.
The researchers are currently performing sub-analyses to help identify factors that might signal which patients are more likely to have a greater return of function after the treatment. “In addition, tools, devices or rehabilitation methods that could potentially improve the likelihood for similar patients to recover with less disability should be investigated,” Morimoto said.