Study in Japan Compares Mechanical Thrombectomy to Standard Therapy in Severe Stroke

February 9, 2022—The American Stroke Association (ASA) announced findings demonstrating that stroke patients previously considered unlikely to survive without severe disability may regain far more function if the blood clots causing ischemic stroke are mechanically removed in addition to standard medical therapy. The preliminary late-breaking research was presented at the ASA’s International Stroke Conference 2022 held February 9-11 both virtually and in person in New Orleans, Louisiana.

According to ASA, the new study in Japan is the first randomized controlled trial to demonstrate the effectiveness of endovascular therapy in patients who have severe strokes involving clots in one or more large brain arteries. ASA noted that the 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.

Shinichi Yoshimura, MD, Professor of Medicine in the Department of Neurosurgery at Hyogo College of Medicine in Nishinomiya, Japan, is the lead author of the study. Takeshi Morimoto, MD, Professor of Medicine in the Department of Clinical Epidemiology at Hyogo College of Medicine, is the study’s senior author.

The study examined blockages that affected more core brain areas—specifically, blockages that scored 3 to 5. The current United States stroke guidelines recommend conducting endovascular therapy for core areas 6 to 9, advised ASA.

As summarized in the ASA press release, this randomized study was composed of 203 stroke patients (average age, 76 years; 44% women) who were treated at 45 hospitals in Japan. Most patients (71%) were examined and had MRI or CT scan of the brain within 6 hours after stroke symptoms were first noticed. The other patients were seen between 6 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 the internal carotid artery, the proximal middle cerebral artery, or both. The strokes were rated as severe (median 22 on the National Institutes of Health NIH Stroke Scale [NIHSS]) and involved disrupted blood flow to large areas of the brain (approximately seven of ten regions).

After imaging, the patients were randomly selected to receive either standard medical care for stroke or standard medical care plus endovascular mechanical thrombectomy performed within 1 hour after imaging. Because of bleeding concerns, intravenous thrombolytic medication was sparingly administered to select patients in a similar proportion in both treatment groups (27 of those received endovascular therapy, and 29 received standard care).

Comparing the 100 patients who received endovascular therapy with the 102 on standard therapy alone, the analysis found the following:

• 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 who received endovascular therapy (14% vs 6.9%) were considered functionally independent (either able to carry out all prestroke activities or a slight disability that did not require daily assistance).
• At 48 hours after treatment, more of the patients who received endovascular therapy (31% vs 8.8%) had major early neurological improvement (improved ability to talk and move limbs).

Additionally, the investigators reported the following outcomes of the safety of adding endovascular therapy versus medical treatment:

• 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% versus 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 (≥ 4 points worsening on the NIHSS), the need for surgery to relieve pressure on the brain in the first week, death within 90 days, or recurrence of ischemic stroke within 90 days.

“I have often encountered a dramatic improvement in a patient just after the mechanical clot removal procedure, even when the infarction area was large,” commented Dr. Yoshimura in the ASA press release. “Yet, patients sometimes also experienced severe hemorrhagic transformation after the artery was reopened. So in Japan, our stroke physicians are always cautious about endovascular therapy when the infarction area is large.”

Dr. Morimoto added, “Our findings confirm that anyone who suffers from stroke should be transferred to a medical facility capable of endovascular therapy as soon as possible. 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.”

Dr. Morimoto continued, “The finding of more intracranial bleeding in the patients who received endovascular therapy is very important. However, there were hemorrhages with symptoms and some that caused no symptoms. The hemorrhages with no symptoms were detected on imaging conducted for this study in the endovascular treatment group, not in the standard practice group. Symptomatic intracranial hemorrhage still occurred more commonly among patients in the endovascular group; however, it was not a statistically significant difference from the standard care group.”

The ASA press release stated that the results of this study may not be generalizable to the United States or western countries because the study was conducted in Japan, where there is less use of intravenous thrombolysis than in the United States and other western countries, and where more strokes are imaged with MRI than CT (perhaps leading to different estimates of how many brain regions are affected by the stroke). Because of these differences in treatment protocols, this study’s results may over- or underestimate the effectiveness of endovascular therapy.

Finally, the ASA advised that the investigators are currently performing subanalyses 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,” stated Dr. Morimoto in the ASA press release.