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International Stroke Conference

Access daily, concise peer-reviewed reports from the International Stroke Conference selected by the Neurology Today editors.

Friday, March 19, 2021

Two different treatment approaches for stroke patients with large vessel occlusion—direct endovascular thrombectomy (EVT) compared with standard care comprising tissue plasminogen activator (tPA) before EVT—showed no differences in outcomes, according to two different studies presented at the International Stroke Conference 2021.

MR CLEAN-NO IV, which was performed in Europe, and SHRINE, conducted mainly in Asia, failed to support direct endovascular therapy as a better treatment. Both trials were also unable to prove the surgery was non-inferior to standard care, reported Yvo Roos, MD, PhD, professor of neurology at the Amsterdam University Medical Center.

 “We did not show superiority or non-inferiority of direct endovascular treatment over intravenous alteplase followed by endovascular treatment. We found similar hemorrhage rates with or without intravenous alteplase administration before endovascular treatment," said Dr. Roos.

In 2015, the benefit of endovascular intervention in acute stroke involving occlusions of large arteries was proven as an addition to alteplase administration within a therapeutic window, noted Dr. Roos. The question since has been if alteplase is needed at all in these cases. Studies have hinted that not using alteplase resulted in the same outcome as using the tissue plasminogen activator, he added.

But, Dr. Roos said, the MR CLEAN-NO IV trial failed to prove that.

Just over 49 percent of the 273 patients assigned to direct endovascular intervention achieved a zero to two score on the modified Rankin Scale at discharge, compared with 51.1 percent among the 266 patients who first received alteplase before undergoing the EVT. The 5 percent greater risk for direct endovascular therapy in the latter group was not statistically significant.

The results did not prove superiority (95% CI 0.65-1.38). The pre-specified margin of non-inferiority was 0.80, indicating that non-inferiority could not be proven either, noted Dr. Roos.

The SHRINE trial had similar results, reported Raul Nogueira, MD, professor of neurology, neurosurgery, and radiology at Emory University in Atlanta.

Dr. Nogueira noted that the trial only applied to centers that could provide thrombectomy-capable services with a fast workflow—not community hospital stroke centers. The SHRINE trial pooled the results of two major trials (SKIP and DEVT) that were conducted in Asia. While the trials hinted that there was a benefit to direct EVT without alteplase on board, the researchers were concerned that the limitations and size of the trial didn't provide a complete picture.

In this trial, the researchers pre-specified that to satisfy non-inferiority hypothesis, the lower boundary of the 95% confidence interval for the primary outcome—a 90-day modified Rankin Score of zero to two—needed to exceed 0.85 in the endovascular group compared to the bridging group, those who received alteplase before endovascular intervention.

In this case, the outcome favored endovascular therapy (adjusted odds ratio 1.23; 95% CI 084-1.92), falling outside the pre-specified margin (p=0.06).

“These studies clearly show that it doesn't matter whether you have tPA first when you perform endovascular procedures on stroke patients," said Louise McCullough, MD, PhD, the Roy M. and Phyllis Gough Huffington Distinguished Chair and professor of neurology at the University of Texas Health Science Center in Houston. “However, I would never withhold tPA unless there was a very clear reason not to such as if the patient had a high rate of bleeding." 

“My preference is always to give a lytic until it is proven that it hurts somebody to do that," Dr. McCullough said. “There are definitely more groin hematomas but the risk of not giving them anything and letting them infarct in some sort of disaster is too big of a risk for me."

Dr. McCullough said one unanswered question is whether one should be using alteplase or tenecteplase. “I think eventually we will shift to tenecteplase because of its ease of use," she said.

Dr. Roos disclosed relationships with industry through the Collaboration for New Treatments of Acute Stroke, which includes non-governmental organizations, government organizations, as well as Medtronic and Top Sector Life Sciences. He is also a shareholder of Nico Lab. Dr. Nogueira disclosed relationships with Stryker Neurovascular, Medtronic, Cerenovus, Phenox, Anaconda, Genentech, Biogen, Prolong Pharmaceuticals, IschemaView, Brainomix, Corindus Vascular Robotics, Vesalio, Viz-AI, Ceretrieve, and Sensome. Dr. McCullough had no disclosures.

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ISC Abstract LB3: LeCouffe NE, Kappelhof M, Treurniet KM, et al, for the MR CLEAN-NO IV Investigators. Intravenous thrombolysis followed by endovascular thrombectomy versus direct endovascular thrombectomy: A randomized controlled trial.

ISC Abstract LB4: Nogueira RG, Kimura K, Matsumaru Y, et al. Systemic thrombolysis randomization in endovascular stroke therapy (SHRINE) collaboration.

Friday, March 19, 2021

An insertable cardiac monitor detected a higher rate of atrial fibrillation (AF) in patients after stroke than routine treatment, according to results presented at the International Stroke Conference 2021.

Among the 242 patients who were fitted with an insertable cardiac monitor, the detection rate for AF was 12.2 percent compared with 1.8 percent in the 250 control group patients, who received standard of care monitoring (hazard ratio 7.41; p<0.001), reported Lee Schwamm, MD, executive vice chairman of neurology at Massachusetts General Hospital/Harvard Medical School.

“We know from many other studies that once established, AF tends to increase in frequency and duration over time," he said. “Therefore, long-term insertable cardiac monitoring should be considered for ischemic stroke patients regardless of the presumed cause of the index stroke."

For the study, Dr. Schwamm and colleagues provided the stroke patients with standard-of-care telemetry while in the hospital and then randomized them to either routine post-discharge monitoring—which could consist of an occasional EKG, Holter monitor, or another infrequent external monitor—versus an insertable cardiac monitor.

The study population included mostly patients over the age of 60 with a presumed large or small vessel occlusion for whom AF was not suspected, and they had to be enrolled in the STROKE AF study within 10 days of experiencing the qualifying stroke. The primary outcome was the AF rate after one year detected by the insertable cardiac monitor group or the standard-of-care group.

“The number of patients monitored to detect one case of atrial fibrillation is eight patients in the insertable cardiac monitor group compared with 56 needed to detect a case of atrial fibrillation in the standard-of-care group," Dr. Schwamm explained.

“In the insertable cardiac monitor patients, there was no meaningful difference in the rate of atrial fibrillation between patients with large vessel disease compared with those with small vessel disease, even though the mechanism of stroke in these patients is believed to be different," he said.

The AF episodes that were reported were not trivial, brief incidents, Dr. Schwamm noted, adding that an estimated 55 percent of patients had an episode that lasted one hour or longer.

Dr. Schwamm said that in the study, when AF was detected, patients who had been on aspirin were then switched to stronger anticoagulants to prevent recurrent stroke. Although the study was not powered to determine if monitoring any subsequent changes in medication prevented recurrent strokes, 15 patients or 6.7 percent of those on the monitor had experienced a recurrent brain attack after 12 months compared with 23 or 9.8 percent of those patients being treated with standard-of-care.

Commenting on the study, Philip  B. Gorelick, MD, MPH, FAAN, adjunct professor of neurology at Northwestern University Feinberg School of Medicine in Chicago, and professor of translational neurosciences at Michigan State University College of Human Medicine in Grand Rapids, said: “A main message from the study is that, about one of eight patients with stroke subtypes in which one does not expect to detect AF, may have or eventually have AF," Dr. Gorelick told Neurology Today At the Meetings.

“Therefore, clinicians should be aware of the long-term risk of AF in these patients, and consider obtaining long-term AF insertable cardiac monitoring, especially if these persons may be at high risk of atrial fibrillation based on a screening score such as the CHADS2VASC score," he said.

“Further follow-up of the cohorts is needed as is information about potential cost and cost-effectiveness of the strategy," Dr. Gorelick said.

Dr. Schwamm disclosed relationships with Medtronic, Penumbra, LifeImage, Medscape, Genentech, Diffusion Pharmaceuticals, and Boehringer-Ingleheim. Dr. Gorelick had no relevant relationships with industry.


For More Information:

ISC Abstract LB6: Schwamm LH, Kamel H, Granger CB, et al. Stroke AF: Atrial fibrillation in non-cardioembolic stroke of presumed known origin.

Friday, March 19, 2021

A stent retriever that an operator can expand and contract mid-procedure resulted in a revascularization rate better than that seen in the trials of already approved, self-expanding stents, according to data presented at the International Stroke Conference.

The devices, called Tigertrievers—which have not yet been approved by the US Food and Drug Administration (FDA)—also resulted in lower levels of disability after three months compared to standard retrievers in the study of acute ischemic stroke patients with large vessel occlusion, researchers said. The study was funded by the device manufacturer, Rapid Medical.

An independent expert said the device has potential but more data are needed.

When using the devices, the operator can slide a button to either widen or compress the wire netting area, to align the device with the vessel dimensions and to adjust the radial force as needed for penetration of the clot and to minimize tension on the vessel wall.

The device was developed to improve upon self-expanding retrievers currently in the marketplace, which have not achieved successful reperfusion about 27 percent of the time, said Jeffrey L. Saver, MD, FAAN, professor of neurology at the David Geffen School of Medicine at UCLA.

Researchers enrolled 160 patients in a lead-in phase and a main phase of the study. Sixteen of the sites were in the US, and one was in Israel, where a single patient was enrolled. Eighty percent of patients had a modified Rankin score of zero before their stroke. Almost all of the others had a score of one.

The investigators compared outcomes to the pivotal trials for the existing stent retrievers already on the market, including the Solitaire and Trevo retrievers.

The patients treated with the operator-adjustable stent retriever had successful revascularization—a grade of 2b or better on the modified Thrombolysis in Cerebral Infarction (TICI) scale—in 84.6 percent of cases, after one to three passes. In the trials of the self-expanding stent retrievers on the market, 73.4 percent had this outcome.

This met a superiority threshold (p=0.0001), said co-primary investigator Rishi Gupta, MD, a vascular neurologist at the Wellstar Health System in Atlanta. In 57.8 percent of the adjustable retriever cases, successful revascularization was achieved on the first pass.

At 90 days, 58 percent of the patients treated with the adjustable retriever had an mRS of zero to two, considered a good outcome. In the trials of the retrievers already on the market, 43 percent had this outcome.

Symptomatic intracranial hemorrhage at 24 hours or mortality at 90 days was seen in 18.1 percent of the adjustable retriever patients, compared to 20.4 percent of those in the trials of the retrievers already on the market, Dr. Saver said.

“The Tigertriever is a highly effective and safe device to remove thrombus in patients with large vessel occlusion who are eligible for mechanical thrombectomy," Dr. Gupta said.

Pooja Khatri, MD, MSc, FAAN, professor of neurology and director of the vascular neurology division at the University of Cincinnati, said the findings show potential, but she reserved judgment about the device.

“The device looks reasonably safe and efficacious," Dr. Khatri said. “It shows potential for being better than prior devices, but that is hard to know with any certainty at this point.  The comparison to historical controls is an apples-to-oranges comparison."

She added that outcomes tend to improve over time, and that analyses that go beyond strictly what is needed for FDA approval are needed.

“We will want to see more analyses ultimately, such as comparison to historical controls with adjustment for important prognostic variables, ideally at the patient level with advanced methods," Dr. Khatri said. “The real-world experiences of our interventional colleagues will be critical, too, of course."

Dr. Khatri said she hoped re-occlusion rates could be reported in the future, imagining that the device could reduce re-occlusion rates due to the control of radial force and less vessel wall damage, but could also increase it if the operator applies too much radial force.

Investigators said they will be able to explore this using vessel imaging studies done at 24 hours.

Dr. Saver disclosed receiving hourly payments and travel reimbursement for service as a scientific consultant advising on rigorous trial design and conduct for Medtronic, Cerenovus, Stryker, Boehringer Ingelheim, and Abbott. Dr. Khatri disclosed that her department has received funds from Cerenovus (grant), Lumosa (consulting), and Diamedica (consulting) on her behalf. She also received funds from Bayer (trial lead), UpToDate (royalties), and Basking (consulting).

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ISC Abstract LB10: Saver JL, Gupta R, Gross B, et al. A new class of radially-adjustable stentrievers for acute ischemic stroke: Primary results of the multicenter Tiger trial.

Friday, March 19, 2021

Stroke patients treated by mobile stroke units received faster treatment and had better outcomes compared to patients who arrived in the standard way to emergency departments (EDs), according to results presented at the International Stroke Conference 2021.

James C. Grotta, MD, FAAN, director of stroke research at the Memorial Hermann-Texas Medical Center and the primary author of the study, said the findings demonstrate the benefits of mobile stroke units, adding to the evidence base that could lead to reimbursement to make their use more widespread.

“A mobile stroke unit is a primary stroke center, basically," Dr. Grotta told Neurology Today At the Meetings. “We get everything done that needs to be done at a primary stroke center."

Mobile units are ambulances equipped to treat patients on board with tissue plasminogen activator (tPA), with a vascular neurologist on board and the ability to do a CT scan and CT angiogram.

In the BEST-MSU study, mobile stroke units were deployed to 911 stroke calls for one week, and patients were treated on board or via telemedicine if they were deemed tPA-eligible. On alternating weeks, the units were not deployed, but staff met the EMS squad and determined whether the patient was tPA-eligible when they arrived on scene, so that the two arms included the same kinds of patients.

In the mobile stroke units, 33 percent of patients were treated during the first 60 minutes—the so-called “golden hour"—compared with just 3 percent of patients treated the standard way; in addition, 97.1 percent of those who were tPA-eligible received tPA in the mobile stroke unit group, compared to 79.1 percent of those in the standard treatment group. Most of that difference, Dr. Grotta said, was probably due to a greater inclination and willingness to use tPA by the mobile stroke unit vascular neurologist, compared to physicians in the ED.

Researchers used a utility-weighted modified Rankin score (uw-mRS), which takes into account patient perceptions about the levels of disability on the scale. For instance, an improvement from four to three—going from being unable to walk to being able to walk—is considered more significant than one to zero—non-significant symptoms versus no symptoms at all. At three months, there was a 0.07 difference in uw-mRS in favor of the mobile stroke unit group (p=0.002).

Based on these results, for every 100 patients treated with a mobile unit rather than standard management, 27 would have less final disability and 11 more will be disability-free, he said.

In the study, the units were used in fairly metropolitan areas, such as Los Angeles and Memphis, Dr. Grotta said, adding the value in rural areas remains to be seen.

Researchers will continue to assess health care utilization related to mobile stroke units for a year. But he said that if a mobile unit is active about half the time it treats 100 patients a year, resulting in 10 more patients completely recovering, that would likely more than cover the cost of the operating units.

“Even with a back-of-the-envelope calculation, I would predict that it's cost-effective to the health care system," he continued.

Commenting on the study, Robert J. Adams, MD, professor of neurology at the Medical University of South Carolina, said the data from this and other studies signal support for more frequent use of mobile stroke units.

“The data are consistent that earlier treatment leads to better outcomes, unless there are more hemorrhages," Dr. Adams told Neurology Today At the Meetings. “This study shows earlier treatment and a qualitative benefit, which is the ability for us to get experience in the 'golden hour.' We have very little data in that time domain. In my mind, these data—and I have been doing this since before there were stroke systems of care, prior to tPA and prior to the stroke certification effort—clearly provide a 'go' signal. These units should be part of the stroke treatment ecosystem."

Using the mobile stroke unit as a primary stroke center “surrogate" in an area with a high stroke rate but no hospital might be a way to increase its value, he said.

“The unit could be placed there more of the time and defer the community cost of building a facility primarily to treat stroke, for example," Dr. Adams said. “Another way to look at this would be for there to be a hefty surcharge to insurance carriers when the unit is used, to increase its ability to generate funds to defer its cost."

Dr. Grotta disclosed receiving a grant for research from Frazer Ltd and Genentech. Dr. Adams disclosed receiving consulting fees from Global Blood Products, a company that makes treatment for sickle cell disease. He has also received travel expenses from Zeriscope, Inc., a company that make mobile telemedicine platforms.

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ISC Abstract LB2: Grotta JC, Parker S, Bowry R, et al. Benefits of stroke treatment delivered by a mobile stroke unit compared to standard management by emergency medical services (BEST-MSU Study).

Friday, March 19, 2021

The gap between the frequency with which people of color receive endovascular therapy (EVT) after stroke, and how often their White counterparts receive it, has closed somewhat since the publication of guidelines encouraging use of EVT in 2015, according to findings presented at the International Stroke Conference 2021. But, the findings show disparities in use of the procedure remain.

Using data from the American Heart Association's Get With the Guidelines-Stroke database, researchers found 14 percent of eligible patients—about 42,000 out of about 303,000—received EVT over the eight-year period studied, ending in 2019. For all patients, the trend for use of EVT increased steadily over that period.

Before 2015, when the guidelines on EVT were updated following trials showing the clinical benefits of the therapy, 32 percent fewer Black patients received EVT than Whites. That gap closed in the period of 2015 and after, when 15 percent fewer Black patients received EVT; still the differences between Blacks and Whites were statistically significant (p<0.0001).

“This is good news but there is work that remains to be done," said Faheem Sheriff, MD, assistant professor of neurology at Texas Tech University Health Sciences Center.

Rates of discharge to hospice or inpatient mortality were better for Blacks compared to Whites both before 2015 and the period of 2015 and later—with an odds ratio of 0.60 and 0.61, respectively—but the scores on tests of function and rates of ambulation were no different for the groups.

At 90 days, the rate of good functional outcomes for Blacks in the period of 2015 and after was 16 percent lower than that of Whites, a statistically significant difference (p=0.006). Before 2015, that difference was 20 percent, which at the time was not a statistically significant difference. In the period 2015 and later, Asians had a 20 percent lower rate of a good functional outcome at 90 days compared to Whites, also significant (p=0.034).

Factors likely contributing to the disparity in EVT use, Dr. Sheriff said, are systemic racism at the structural and provider level, lower use of ambulance services and later arrival to centers capable of performing EVT, lack of awareness of stroke symptoms, and mistrust of the health care system due to historic inequalities.

“There needs to be concerted efforts to convert these observations of racial and ethnic disparities into actions," he said. “Such a life-saving therapy needs to be more uniformly distributed and more uniformly available to ensure that the benefits are available to all groups."

The conference program director, Louise McCullough, MD, PhD, the Roy M. and Phyllis Gough Huffington Distinguished Chair and professor of neurology​ at the​ University of Texas Health Sciences Center at Houston, said that even though disparities remain, the data tell a “great news story."

“We're paying attention to it, and we're measuring it," Dr. McCullough said. “The fact that the gap has narrowed so much in the past five years is also really, really encouraging."

Deeper understanding of hurdles will be important in continuing to make progress, she said.

“I think it will be very important to engage the communities, go to where the people are, to really do education, get community buy-in, making sure that our most vulnerable populations are well-represented and we hear what they're saying, what their barriers are," she said. For instance, in underserved populations, people may not be inclined to call an ambulance because they will be “stuck with a very large bill," Dr. McCullough said.

Dr. Sheriff said that as attempts are made to continue to narrow the gap in EVT utilization, it's important to understand how the gains were accomplished in the first place, so that the gains are not lost.

“I think it's a good news story and I think we need to capitalize upon it," he said. He stressed the importance of “race- and ethnicity-specific awareness, where you target all parts of the community but tailor it to socioeconomic factors and cultural factors to boost uptake."​

“Those educational campaigns, in my opinion," he said, “have had the greatest impact in terms of utilization of all stroke therapies, endovascular therapy included."

Drs. Sheriff and McCullough had no disclosures.

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ISC Abstract LB9: Sheriff F, Xu H, Cruz-Flores S, et al. National temporal tends in endovascular therapy (EVT) utilization and outcomes according to race and ethnicity: Findings from Get With the Guidelines (GWTG)-stroke.