10 Late-Breaking Science presentations highlight Closing Main Event
Late-Breaking Science presented during Friday’s Closing Main Event revealed that:
- Embolization as an adjunct to surgery for subacute and chronic subdural hematoma reduces reoperation.
- MAGIC-MT confirmed MMA embolization better than surgery alone for chronic subdural hematoma in large population.
- STEM showed significant benefit for embolization in chronic subdural hematoma versus best medical/surgical care.
- STOP-CAD showed anticoagulation can reduce ischemic risk following cervical artery dissection.
- A novel monoclonal antibody selectively blocks blood-brain barrier disruption by VEGF following ischemic stroke in nonhuman primates.
- CHABLIS-T II showed better reperfusion for tenecteplase versus conventional medical treatment for large vessel occlusion.
- Smartphone app can detect stroke with 99% sensitivity.
- RAISE demonstrated superior functional outcomes for reteplase versus alteplase.
- INSPIRES showed significant benefit from DAPT + immediate, intensive statin therapy for mild ischemic stroke/TIA.
- SELECT2 confirmed one-year safety, efficacy of thrombectomy for large core ischemic stroke.
The EMBOLISE, MAGIC-MT and STEM Late-Breaking Science presentations studied different aspects of embolization versus surgical care.
EMBOLISE
The largest U.S.-based randomized trial exploring embolization for subacute and chronic subdural hematoma (SDH) showed a significantly lower rate of recurrence or progression compared to surgery, 4.1% versus 11.3%, p=0.0081. The Onyx™ Liquid Embolic System also showed noninferiority in the deterioration of neurologic function versus surgery, 11.8% versus 9.8%, p<0.0001, with no difference in 90-day mortality between the two groups. Onyx™, an ethylene vinyl alcohol copolymer dissolved in dimethyl sulfoxide, is currently approved for the treatment of cerebral arteriovenous malformations.
Jason Davies, MD, PhD
“One of the challenges of conducting this trial was dealing with a frail elderly population, especially in the middle of the pandemic” said Jason Davies, MD, PhD, associate professor of neurosurgery and biomedical informatics at the State University of New York at Buffalo. “Tracking patients down for follow-up is always a challenge, and these were compounded by the various COVID-era restrictions that many of our sites faced.”
The Embolization of the Middle Meningeal Artery with ONYX™ Liquid Embolic System for Subacute and Chronic Subdural Hematoma (EMBOLISE) trial randomized 400 patients across 39 U.S. centers to receive surgery with adjunctive middle meningeal artery (MMA) embolization, the experimental group, or surgery alone. The mean age of patients was about 72 years and 27% were female.
The primary endpoint was the rate of hematoma recurrence/progression requiring surgical drainage between the two arms. Secondary endpoints included clinical, radiographical and health economic outcomes. Safety evaluations included rates of neurological death and device- or procedure-related adverse events.
There were no Onyx™ device-related adverse events through 90 days, Dr. Davies reported, and the experimental group had fewer serious adverse events related to surgery compared to the surgery-only group at 30 days, 15.7% versus 21.7%. The rates of neurological death at 90 days were similar, 4.6% in the experimental group versus 2.0% in the surgical group, p=0.17. None of the neurological deaths in the experimental group were related to the Onyx™ device or the MMA embolization procedure.
“There have been a lot of small institutional studies and case series that have used a variety of different embolic agents, plastic particles, glues, gelatin sponges, liquid agents, and so far it seems that whatever agent you use, patients do better with embolization,” Dr. Davies said. “There are a number of concurrent randomized trials using some of these different agents, and we look forward to seeing the results of those. We still have an observational arm active with patients who don’t immediately require surgery to see if embolization can prevent them from undergoing surgery. I think surgery is going to become dramatically less common for SDH.”
Middle meningeal artery embolization superior to surgery to prevent recurrent chronic subdural hematoma
The largest clinical trial to date comparing middle meningeal artery (MMA) embolization to conventional surgical treatment for chronic subdural hematoma (CSDH) found that MMA embolization reduced the rate of recurrence/progression by 4.93% versus surgery alone (95% CI -9.37 to -0.63, p=0.02). MMA embolization also showed fewer adverse events, odds ratio 0.54 (95% CI 0.32-0.92, p=0.02) with no significant difference in mortality.
“Among patients with symptomatic non-acute subdural hematoma, the addition of middle meningeal artery embolization is superior to usual care alone, producing less hematoma recurrence or progression, or death, within 90 days,” said Ying Mao, MD, PhD, professor of neurosurgery, Huashan Hospital, Fudan University in Shanghai, China.
Ying Mao, MD, PhD
CSDH accounts for about 10% of all intracranial hematomas, Dr. Mao said, with an annual incidence of 3-5.4/100,000. Despite high incidence, high recurrence and high mortality, clinicians have just three treatment options: drug treatment with atorvastatin, surgery or MMA embolization. The managing non-acute SDH using liquid materials; a Chinese randomized trial of MMA Treatment (MAGIC-MT) compared MMA embolization to surgery, either as a standalone procedure or as an adjunct to surgery versus surgery alone. None of the previously published studies of MMA embolism were randomized controlled trials.
MAGIC-MT randomized 722 patients at 31 centers across China, 365 to MMA embolization and 362 to conventional treatment. A total of 281 patients in the MMA embolization group also underwent surgery. Patients’ median age was 68-70 years and about 83% were male.
The primary outcome was symptomatic recurrence or progression of subdural hematoma (SDH) or death within 90 days of randomization. Safety endpoints included serious adverse events and SDH-related mortality at 90 and 360 days, and severe surgery-related complications at 30 days.
The benefit of MMA embolization over usual care was more pronounced in patients who received embolization alone, without surgery, OR=0.34 (95% CI 0.126-0.934) and those without known head trauma, OR=0.42 (95% CI 0.193-0.926).
Dr. Mao noted that the results of MAGIC-MT need confirmation in further clinical trials.
Positive results for novel liquid embolic to treat chronic subdural hematoma
Embolization of the middle meningeal artery is an increasingly common approach to the treatment of chronic subdural hematoma (CSDH). A variety of mechanical and occlusive materials are in use, including liquid embolic agents. Initial results for Squid, a novel liquid embolic, showed an odds ratio of 3.60 (95% CI 1.91-6.78, p=0.0001) for reduction in SDH recurrence or re-accumulation compared to standard medical and surgical care. This was accomplished without a significant increase in stroke or death compared to the control group.
Adam Arthur, MD, MPH
“We have been treating subdural hematoma largely the same way for at least 7,000 years,” said Adam Arthur, MD, MPH, chair of neurosurgery at the University of Tennessee Health Sciences Center and Semmes-Murphy Neurologic and Spine Institute. “We have radiocarbon-dated skulls with holes that are pretty much the exact size and shape of skull openings we currently make. About 10 years ago, researchers started to consider taking an endovascular route and sealing off the abnormally fragile blood vessels growing from the inside of the dura that give rise to these chronic hematomas.”
Squid is an ethylene vinyl alcohol copolymer that has been in use in Europe for more than a decade but is an investigational device in the United States. Like other liquid embolics, it precipitates upon exposure to blood in an outside-in pattern to form a sponge-like gel that blocks blood vessels.
The SQUID Trial for the Embolization of the Middle Meningeal Artery for Treatment of Chronic Subdural Hematoma (STEM) randomized a total of 310 patients with cSDH at centers in Europe and the United States to Squid versus standard of care, the treatment team’s choice of medical or surgical treatment. The primary outcome was treatment failure, defined as the occurrence of residual or re-accumulation of SDH ≥10 mm, reoperation or surgical rescue after the index procedure, any new, major disabling stroke, myocardial infarction or death from any neurological cause within 180 days of intervention. The primary safety endpoint was major disabling stroke or death.
At six months, the treatment arm of the study had 15.2% treatment failures versus 39.2% for standard of care, OR=3.60 (95% CI 1.91-6.78, p=0.0001). Subgroup analysis showed that while MMA embolization had a nonsignificant benefit compared to surgery (OR=2.4 95% CI 0.97-6.03, p=0.058), embolization was dramatically better than non-surgical management, OR=6.1 (95% CI 2.43-15.4, p=0.0001).
“This evidence should change clinical practice,” Dr. Arthur said. “Clinical practice may already be changing because this is a very forward-thinking area of medicine. Articles in the literature demonstrate that physicians have already begun using this treatment even though randomized controlled trials were not done yet.”
30-day anticoagulation may reduce ischemic stroke risk following cervical artery dissection
A large retrospective study of anticoagulation versus antiplatelet therapy following cervical artery dissection (CAD) suggests that 30 days of anticoagulation may reduce ischemic stroke events without increased bleeding risk. Extending anticoagulation beyond 30 days increases the risk of hemorrhage.
“Cervical artery dissection accounts for about 2% of strokes but is one of the most common causes of stroke and disability in the younger population,” said Shadi Yaghi, MD, associate professor of neurology at Brown University Alpert Medical School. “Knowing the best treatment strategy for these younger patients would have a significant clinical impact.”
Shadi Yaghi, MD
Dr. Yaghi is also co-director of the Rhode Island Hospital Comprehensive Stroke Center and director of Vascular Neurology at Lifespan.
The STOP-CAD study included 3,631 patients presenting at 63 acute hospitals across 16 countries who were diagnosed with CAD without major trauma and confirmed by imaging. A total of 402 patients were treated with anticoagulation, 2,453 with antiplatelet therapy, and 781 received both treatments.
Patients had a mean age of 47 years and 54% were male.
Anticoagulation was either parenteral with heparin or low molecular weight heparin or oral with a vitamin K antagonist or a direct acting oral anticoagulant. Antiplatelet treatment was either dual or single agent therapy.
The primary outcomes were ischemic stroke and major hemorrhage during follow-up up to 180 days after CAD diagnosis.
There were 162 ischemic strokes (4.4%) and 28 major hemorrhages (0.8%) within 180 days. Most of the ischemic strokes, 87%, occurred within the first 30 days.
Anticoagulation showed a numeric, non-significant trend for lower risk of ischemic stroke at 30 days, HR=0.68, 95% CI 0.44-1.05 (p=0.084). There was no difference in the risk for stroke between the anticoagulation and antiplatelet therapy within 180 days, HR=0.83, 95% CI 0.56-1.21 (p=0.239). Anticoagulation was also associated with a significant risk of major hemorrhage at 180 days, HR= 7.46, 95% CI 1.83-30.33 (p=0.005) but not at 30 days, HR=1.11, 95% CI 0.40-3.08 (p=0.841).
Interaction analysis found a significant association between anticoagulation and occlusive dissection for reduced risk of ischemic stroke, HR=0.40, 95% CI 0.18-0.89 (p for interaction=0.009). There was no reduction in risk for ischemic stroke with non-occlusive dissections, HR=1.23, 95% CI 0.77-1.98.
Dr. Yaghi noted that STOP-CAD findings are similar to TREAT-CAD and CADISS findings of fewer ischemic events and more frequent major bleeding events with anticoagulation versus antiplatelet therapy.
“The most important message from STOP-CAD is that if you are anticoagulating after a cervical arterial dissection, consider stopping after 30 days to lower the risk of bleeding,” he said. “Patients who had an occlusive dissection had the most benefit from anticoagulation.”
New mAb selectively blocks blood-brain barrier disruption of VEGF to reduce ischemic stroke volume, edema, necrosis in animal models
Vascular endothelial growth factor A (VEGF) plays a dual role in ischemic stroke, producing pro-angiogenic neuroprotective effects and disrupting the blood-brain barrier (BBB) to promote vasogenic edema and an influx of protein-rich extravasate into the brain parenchyma. A novel monoclonal antibody, anti-Sdc2, selectively blocks BBB effects and reduces vasogenic edema in mice and non-human primates without affecting the neuroprotective effects of VEGF following ischemic stroke.
“VEGF is a potent inducer of BBB disruption and vasogenic edema and is upregulated in stroke,” said Federico Corti, PhD, associate research scientist in Prof. Michael Simons’ laboratory at Yale University School of Medicine. “VEGF disrupts the BBB to allow reactive oxygen species and other blood-borne substances to infiltrate into the parenchyma. That BBB disruption, in addition to ischemic conditions that already exist, physically deteriorates, and worsens the effects of ischemia beyond the ischemic core into the penumbra and farther to produce additional necrosis in the parenchyma. Anti-Sdc2 antibodies produced significant reductions in stroke volume, edema, and necrosis as long as 72 hours post-stroke in our models.”
Federico Corti, PhD
VEGF is the key endothelial growth factor that regulates capillary bed growth and expansion, maintains survival of existing blood vessels. VEGF has long been recognized as a potent inducer of vascular permeability in the brain and other vascularized tissues, Dr. Corti said. Although there are several other biologic substances that can induce vascular leak, VEGF is the principal regulator of vascular permeability in injury and ischemia settings.
The vascular and neuroprotective effects of VEGF rule out the use of currently available anti-VEGF drugs, such as bevacizumab and aflibercept, that inhibit all of its functions. The effects of VEGF on BBB persist for days, perhaps longer. Anti-Sdc2 selectively regulates the vascular permeability effects of VEGF while leaving its vascular protective and neuroprotective signaling pathways intact.
Anti-Sdc2 completely blocks VEGF-induced breakdown of BBB and vasogenic edema following induced stroke in mice. A fully humanized version mAb was tested in African green monkeys following ischemic stroke induced by mid-MCA ligation for three hours. Anti-Sdc2 or vehicle was administered at the time of reperfusion (early treatment) or three hours post-reperfusion (delayed treatment). Stroke volume was assessed by MRI at baseline, 24 hours and 72 hours.
The early treatment group showed a 58.1% reduction in stroke volume at 24 hours and 33.8% at 72 hours versus vehicle. The delayed treatment group showed a 91.3% reduction in stroke volume at 24 hours and 55.5% at 72 hours. Histological analysis confirmed significant reductions in edema and necrosis in both treatment groups.
“Vasogenic edema begins within hours of an ischemic stroke, but continues to increase over at least a week, offering an extended therapeutic window,” Dr. Corti said. “Our findings suggest that anti-Sdc2 promotes neuroprotection after ischemic stroke and suggest it could be useful in patients undergoing early perfusion as well as outside current reperfusion window guidelines.”
Tenecteplase beats best medical treatment for large vessel occlusion up to 24 hours after acute ischemic stroke
Initial results of the CHABLIS-T II trial showed tenecteplase was more effective for major reperfusion following acute ischemic stroke with large vessel occlusion up to 24 hours after last known well versus conventional medical treatments. Compared to clinician’s choice of aspirin, tissue plasminogen activator, urokinase or thrombectomy, intravenous tenecteplase demonstrated a 3-fold higher rate of reperfusion without symptomatic intracranial hemorrhage, adjusted relative risk (aRR)=3.0 (95% CI 1.5-5.7, p=0.001). There were no significant differences in hemorrhage or clinical efficacy between the groups.
“One of the most surprising aspects is that tenecteplase showed such significant advantage over the best medical treatment regarding reperfusion with a relatively low risk of hemorrhagic events,” said Xin Cheng, MD, PhD, associate professor of neurology at Huashan Hospital at Fudan University in Shanghai, China. “However, the advantage of reperfusion did not translate into a smaller volume of infarct growth and a better clinical outcome. Detailed post-hoc analysis is warranted to further explore this discrepancy.”
Tenecteplase has already been shown to be non-inferior to the usual thrombolytic agent, alteplase, in acute ischemic stroke when given within 4.5 hours of last known well, Dr. Cheng said, and has largely replaced alteplase for ease of administration, a single bolus versus a 60-minute infusion. But there have been no positive findings for tenecteplase in patients with large vessel occlusion beyond the 4.5-hour window, possibly due to the effects of endovascular treatment.
Xin Cheng, MD, PhD
CHABLIS-T II randomized 224 acute ischemic stroke patients to a single weight-based bolus of tenecteplase (111 patients) versus clinician’s treatment of choice (113 patients) at 23 stroke centers across China. All patients had large vessel occlusion and favorable penumbral profile confirmed by imaging. The primary outcome was achieving major reperfusion without symptomatic intracranial hemorrhage at 24-48 hours after randomization.
Secondary outcomes included recanalization, infarct growth, major neurological improvements, change in National Institutes of Health Stroke Scale score, hemorrhagic transformation at 24-48 hours, systematic bleeding at discharge, modified Rankin Scale (mRS) 0-1, mRS 0-2, mRS 5-6, mRS distribution and Barthel index at 90 days.
The primary outcome occurred in 33.3% of tenecteplase patients versus 10.6% of best medical treatment patients, Dr. Cheng reported. Tenecteplase resulted in a superior rate of recanalization, 35.1% versus 14.2%.
“We hope that this trial can encourage the use of tenecteplase in acute stroke patients beyond the 4.5-hour time window, especially for patients in areas without access to endovascular treatment,” Dr. Cheng said. “Thrombolysis with tenecteplase in the extended time window with simplified imaging selection might be worthwhile for future trials.”
FAST-based smartphone app can reliably detect stroke
The FAST acronym — Face, Arm, Speech, Time to call 911 — has been used to promote stroke detection with minimal results. A novel smartphone app based on machine learning, FAST-AI, can detect stroke based solely on facial imaging, a few words of speech and arm movement as captured by device sensors with 99% sensitivity and 90% sensitivity.
“Despite the efforts of multiple organizations, FAST has not led to a significant increase in stroke recognition, because it relies of human intelligence to remember the acronym and to apply it,” said Radoslav I. Raychev, MD, associate professor of neurology at the University of California Los Angeles. “We decided to automate FAST using smartphones because they are extremely common in peoples’ day-to-day routines across the world.
Radoslav I. Raychev, MD
Researchers worked with 400 stroke patients and 71 healthy controls at five metropolitan stroke centers to correlate visual data across 90 landmark facial points, arm movement as measured by phone accelerometers and gyroscopes, and recorded voice patterns with neurological impressions of stroke versus no stroke and stroke versus Bell’s palsy. All of the tests for stroke patients were conducted within 72 hours of symptom onset.
The facial model has been trained to detect asymmetry and can identify which side of the face has been affected by stroke with 92% sensitivity and 78% specificity. The model can also distinguish asymmetry due to stroke from asymmetry due to Bell’s palsy.
The arm movement model detects any significant variance in motion direction, height and acceleration of a smartphone held in each hand successively and raised up and down again with 78% sensitivity and 79% specificity. Differences in the measured movements can be analyzed to detect arm weakness irrespective of grip strength or smartphone orientation.
The speech model uses extracted Mel-frequency cepstrum coefficients that represent the short-term power spectrum of sounds, including speech. Normal speech and slurred speech produce markedly different cepstrums that can be captured automatically with 75% sensitivity and 75% specificity.
Most of the stroke patients, 70%, were used to train the machine learning algorithms. The remainder were used to test and validate the algorithms against neurologists’ clinical impressions.
The initial results were achieved using speakers of Bulgarian, Dr. Raychev said. The next step is to expand the speech algorithm to English, Spanish and other common global languages as steps toward developing a language-independent model.
“Our first iteration will be a clinician aid and rolled out to EMTs, paramedics and other responders to expand their neurological examination capabilities,” he said. “Our ultimate goal is to develop platform-independent, consumer-facing technology that can be used any time there is any question or concern of a stroke by active self-testing, or even as an ambient monitoring tool in smart home systems, autonomous driving vehicles, video conferencing and more.”
Reteplase superior to alteplase for thrombolysis following acute ischemic stroke
The largest head-to-head trial to date of reteplase versus alteplase for intravenous thrombolysis following acute ischemic stroke showed clear superiority in functional outcomes for a double fixed-dose bolus of reteplase over weight-based dosing of alteplase. In this trial, reteplase showed a 9.0% improvement in modified Rankin Scale (mRS) of 0-1 at 90 days compared to alteplase. Reteplase also showed higher bleeding rates compared to alteplase and similar 90-day mortality. Reteplase is currently indicated for acute myocardial infarction.
“The demand for intravenous thrombolysis in acute ischemic stroke has significantly increased with the continuous improvement of stroke care quality,” said Yongjun Wang, MD, PhD, professor, chief neurologist and president of Beijing Tian Tan Hospital at China National Clinical Research Center for Neurological Diseases in Beijing, China. “There is an ongoing need to extend reperfusion therapy to a larger proportion of patients. Reteplase, which is more convenient and cost-effective, has superior efficacy and comparable fatality safety profiles as compared to alteplase. These overall findings should encourage the administration of reteplase in appropriate patients with acute ischemic stroke.”
Reteplase has a five-fold longer plasma half-life compared to alteplase, 14-18 minutes versus 3-4 minutes, Dr. Wang noted. This longer half-life allows reteplase to be administered as a fixed-dose bolus rather than the weight-based infusion used for alteplase. The fixed-dose bolus regimen is more convenient and can be administered more quickly because individualized dosing calculations are not needed.
The Reteplase versus Alteplase for Acute Ischemic Stroke (RAISE) trial randomized a total of 698 patients to reteplase and 698 patients to alteplase, a total of 1,396 patients at 62 centers across China. Efficacy results are based on a modified intention-to-treat population of 1,396 patients, 698 in each arm, while the safety population included 1,399 patients, 700 in the reteplase arm and 699 in the alteplase arm. 
Yongjun Wang, MD, PhD
Patients were enrolled and treated within 4.5 hours of symptom. A double bolus of reteplase is used for acute myocardial infarction to minimize early reocclusion of the infarct-related artery; RAISE used a similar double-bolus regimen.
The primary outcome was the proportion of patients with mRS of 0-1 90 days after treatment. Safety outcomes included all-cause mortality, percentage of patients with symptomatic intracranial hemorrhage (sICH) and other bleeding events .
The primary outcome, mRS of 0-1, was seen in 80.1% of the reteplase arm versus 71.1% of the alteplase arm, risk ratio (RR)=1.13 (95% CI, 1.03 - 1.23). sICH was observed in 2.4% of patients in the reteplase group and 2.1% of patients in the alteplase group within 36 hours from disease onset, RR=1.131 (95% CI 0.54 - 2.75). There were significantly higher rates of intracranial hemorrhage in the reteplase arm, 7.7% versus 4.9%, and clinical related non-massive hemorrhage, 5.4% versus 2.4%, and no difference in all-cause mortality at 90 days.
“Considering reteplase’s better efficacy, it is worthwhile to assess the efficacy and safety of intravenous reteplase with an extended time window from 4.5 hours to 24 hours,” Dr. Wang said. “Potential future research also includes identifying patients who are at higher risk of bleeding with reteplase.”
Intensive statin + DATP improves functional outcomes, secondary prevention after mild ischemic stroke or TIA
Global guidelines recommend dual antiplatelet therapy (DAPT) for secondary stroke prevention in individuals following a minor ischemic stroke or high-risk transient ischemic attack (TIA), but the risk of recurrent stroke remains high, as much as 12.5% at one year. Guidelines also recommend intensive statin therapy for secondary stroke prevention. The largest trial to combine both intensive statins and DAPT showed the combination reduced the risk of recurrent stroke by 24% and the risk of poor functional outcomes by 28% versus aspirin and delayed intensive statins. Combination therapy also increased the risk of moderate-to-severe bleeding.
“Patients within 72 hours of mild ischemic stroke or TIA of presumed atherosclerotic cause can benefit from the combination of clopidogrel-aspirin DATP and immediate intensive statin treatment,” said Yuesong Pan, MD, PhD, China National Clinical Research Center for Neurological Diseases at Beijing Tiantan Hospital at Capital Medical University in Beijing, China. “Nevertheless, the observed increase of moderate-to-severe bleeding should be considered when combined treatment is administered in clinical practice.”
Yuesong Pan, MD, PhD
The Intensive Statin and Antiplatelet Therapy for High-risk Intracranial or Extracranial Atherosclerosis (INSPIRES) trial randomized a total of 6,100 patients to a 2x2 factorial design of clopidogrel plus aspirin or aspirin along with immediate intensive statin or delayed intensive statin across 222 hospitals in China from September 2018 to October 2022. All of the patients were within 72 hours of a mild ischemic stroke (NIHSS score ≤5) or high-risk TIA (ABCD score ≥4) of presumed atherosclerotic cause.
The primary endpoint was the incidence of new stroke within 90 days with poor functional outcome as a key secondary endpoint. Moderate-to-severe bleeding was the primary safety outcome.
Among patients in the DAPT + immediate intensive statin group, 7.6% had a new stroke within 90 days versus 9.9% in the aspirin + delayed intensive statin group, HR=0.76 (95% CI 0.60-0.97, p=0.03). Poor functional outcomes were documented in 9.5% and 12.5% of the groups, respectively, HR=0.72 (95% CI 0.57-0.90). Moderate-to-severe bleeding occurred in 1.1% and 0.5% of the groups respectively (p=0.047).
Reduction in stroke risk was driven largely by the clopidogrel-aspirin combination, Dr. Pan said, as was the increase in bleeding risk.
“Secondary analysis suggested that the improvement in functional outcomes at 90 days might be partially achieved due to the neuroprotective effects of immediate statin administration,” he said. “However, this needs further validation.”
One-year results show thrombectomy safe, effective for large-core ischemic strokes
The SELECT2 trial of endovascular thrombectomy (EVT) to treat ischemic strokes with large cores was stopped early for efficacy and 90-day results showed significant clinical and quality-of-life benefits. One-year follow-up data confirmed the procedure is more effective than medical management alone for improved modified Rankin Scale (mRS) score distribution, functional independence, independent ambulation, and quality-of-life scores for mobility, depression, social domains and cognitive domains. There was no difference in mortality between EVT versus medical therapy alone. 
Amrou Sarraj, MD, FAHA
“These results, in conjunction with the primary results from all large core trials, establish the efficacy and safety of thrombectomy in patients with large-core strokes,” said Amrou Sarraj, MD, FAHA, FSVIN, professor of neurology at Case Western Reserve University School of Medicine, the George M. Humphrey II Endowed Chair at the University Hospitals Neurological Institute, and director of the University Hospitals Comprehensive Stroke Center and Stroke Systems. “Efforts are already ongoing to include the thrombectomy procedure as a standard of care in upcoming societal guidelines. These results also characterize the need to capture long-term outcomes in a population that may demonstrate continued improvement in clinical outcomes.”
SELECT2 randomized 178 patients to EVT versus 174 patients to medical management at 31 hospitals in Australia, Europe, North America and New Zealand within 24 hours of onset of ischemic stroke due to proximal occlusion of the internal carotid artery or the first segment of the middle cerebral artery. All patients had a large ischemic core on non-contrast CT (ASPECTS of 3-5) or measuring ≥mL on CT-perfusion/MRI. Patients were randomized and treated between October 2019 and September 2022. One-year follow-up was completed for 93% of patients in October 2023.
Thrombectomy showed a significantly improved mRS distribution, Wilcoxon-Mann-Whitney probability of superiority=0.59 (95% CI 0.53-0.64, p=0.0019) and generalized odds ratio=1.43 (95% CI 1.14-1.78) versus medical management. Thrombectomy patients were also likely to achieve functional independence, risk ratio (RR)=3.7 (95% CI 1.90-5.80) and independent ambulation, RR=1.88 (95% CI 1.36 -2.59) versus medical management.
Mortality at one year was similar, 45% for EVT and 52% medical management, RR=0.89 (95% CI 0.71-1.11). Dr. Sarraj reported that results from both the as-treated and per-protocol populations were supportive of the primary conclusions.
“These results provide the first confirmation of long-term benefits of thrombectomy in patients with large-core strokes and are consistent with similar long-term benefits in those with small-core strokes,” he said. “Now that the long-term outcomes of thrombectomy are established, our goals are to further identify and characterize key elements of thrombectomy treatment effects, including prognostication of outcomes, identifying patients who can further benefit from potential reperfusion and other adjunct therapies such as neuroprotection to further support individualized decision making.”
SELECT2 was published simultaneously in The Lancet.
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