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Predictors of ICH after thrombectomy identified
(ICH), new research suggests. In a study of nearly 600 patients undergoing thrombectomy, investigators combined a modified Thrombolysis in Cerebral Ischemia (TICI) score, an Alberta Stroke Program Early Computed Tomography Score (ASPECTS), and glucose levels (the “TAG score”) to predict risk. Results showed that each unit increase in the combination score was associated with a significant, nearly twofold greater likelihood of symptomatic ICH.
“It is very easy” to calculate the new score in a clinical setting, lead author Mayra Johana Montalvo Perero, MD, Department of Neurology, Brown University and Rhode Island Hospital, Providence, said. “You just need three variables.”
The findings were presented online as part of the 2020 American Academy of Neurology Science Highlights.
Limited data
High TAG scores are associated with symptomatic ICH in patients receiving mechanical thrombectomy, Dr. Montalvo Perero and colleagues said.
Although clinical predictors of symptomatic ICH are well established, “there is limited data in patients who underwent mechanical thrombectomy,” the researchers noted.
To learn more, they assessed 578 patients (52% women; mean age, 73 years) who had mechanical thrombectomy for acute ischemic stroke at a comprehensive stroke center. Within this cohort, 19 patients (3.3%) developed symptomatic ICH.
The investigators compared clinical and radiographic findings between patients who experienced symptomatic ICH and those who did not.
The TICI score emerged as a predictor when each unit decrease in this score was associated with greater risk for symptomatic ICH (odds ratio, 5.13; 95% confidence interval, 1.84-14.29; P = .002).
Each one-point decrease in the ASPECTS score also predicted increased risk (OR, 1.52; 95% CI, 1.1-2.0; P = .003).
“The main driver is the size of the stroke core, which is correlated with the ASPECTS score,” Dr. Montalvo Perero said.
Each 10 mg/dL increase in glucose level also correlated with increased risk (OR, 1.07; 95% CI, 1.01-1.13; P = .018).
Twice the risk
The investigators then combined these three independent variables into a weighted TAG score based on a multivariate analysis. Each unit increase in this composite score was associated with increased risk of symptomatic ICH (OR, 1.98; 95% CI, 1.48-2.66; P < .001).
There was no association between patients who received tissue plasminogen activator (tPA) and risk of symptomatic ICH, which Dr. Montalvo Perero said was surprising.
However, “that may be due to a small number” of patients with symptomatic ICH included in the study, she said. “Therefore, that would be an interesting question to ask in future studies with bigger cohorts.”
Larger studies are also needed to validate this scoring system and to test strategies to reduce risk of symptomatic ICH and make thrombectomy safer in patients with elevated TAG scores, Dr. Montalvo Perero said.
A step in the right direction?
Commenting on the study, Jeremy Payne, MD, PhD, director of the Stroke Center at Banner Health’s University Medicine Neuroscience Institute in Phoenix, Arizona, noted the importance of predicting which patients might have secondary bleeding after interventional treatment of a large vessel occlusion stroke
“In aggregate, the role of endovascular thrombectomy is quite clear, but we still struggle to predict at the individual patient level who will benefit,” said Dr. Payne, who was not involved with the research.
Transfer and treatment of these patients also carries an economic cost. “Just getting patients to our center, where about 80% of the complex stroke patients come by helicopter, costs upwards of $30,000,” Dr. Payne said. “The financial argument isn’t one we like to talk much about, but we’re committing to spending probably $100,000-$200,000 on each person’s care.”
This study “attempts to address an important issue,” he said.
Predicting who is more likely to benefit leads to the assumption that if that were to happen, “we could skip all the rigamarole of helicopters and procedures, avoid the extra expense and particularly not make things worse than they already are,” explained Dr. Payne.
Potential limitations include that this is a single-center study and is based on an analysis of 19 patients out of 578. As a result, it is not clear that these findings will necessarily be generalizable to other centers, said Dr. Payne.
The TICI and ASPECTS “are pretty obvious markers of risk,” he noted. “The glucose levels, however, are more subtly interesting.”
He also pointed out that an association between diabetes and worse stroke outcomes is well established.
“The mechanisms are poorly understood, but the role of glucose keeps popping up as a potential marker of risk, and so it’s interesting that it bubbles up in their work too,” Dr. Payne said.
Furthermore, unlike TICI and ASPECTS, glucose levels are modifiable.
“Overall, then, we will continue to study this,” Dr. Payne said. “It’s very important to refine our ability to predict which patients may receive benefit versus harm from such procedures, and this is a step in the right direction.”
Some findings were also published December 2019 in the Journal of Neurology, Neurosurgery & Psychiatry.
Montalvo Perero and Payne have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
SOURCE: Motalvo Perero MJ et al. AAN 2020, Abstract S20.001.
(ICH), new research suggests. In a study of nearly 600 patients undergoing thrombectomy, investigators combined a modified Thrombolysis in Cerebral Ischemia (TICI) score, an Alberta Stroke Program Early Computed Tomography Score (ASPECTS), and glucose levels (the “TAG score”) to predict risk. Results showed that each unit increase in the combination score was associated with a significant, nearly twofold greater likelihood of symptomatic ICH.
“It is very easy” to calculate the new score in a clinical setting, lead author Mayra Johana Montalvo Perero, MD, Department of Neurology, Brown University and Rhode Island Hospital, Providence, said. “You just need three variables.”
The findings were presented online as part of the 2020 American Academy of Neurology Science Highlights.
Limited data
High TAG scores are associated with symptomatic ICH in patients receiving mechanical thrombectomy, Dr. Montalvo Perero and colleagues said.
Although clinical predictors of symptomatic ICH are well established, “there is limited data in patients who underwent mechanical thrombectomy,” the researchers noted.
To learn more, they assessed 578 patients (52% women; mean age, 73 years) who had mechanical thrombectomy for acute ischemic stroke at a comprehensive stroke center. Within this cohort, 19 patients (3.3%) developed symptomatic ICH.
The investigators compared clinical and radiographic findings between patients who experienced symptomatic ICH and those who did not.
The TICI score emerged as a predictor when each unit decrease in this score was associated with greater risk for symptomatic ICH (odds ratio, 5.13; 95% confidence interval, 1.84-14.29; P = .002).
Each one-point decrease in the ASPECTS score also predicted increased risk (OR, 1.52; 95% CI, 1.1-2.0; P = .003).
“The main driver is the size of the stroke core, which is correlated with the ASPECTS score,” Dr. Montalvo Perero said.
Each 10 mg/dL increase in glucose level also correlated with increased risk (OR, 1.07; 95% CI, 1.01-1.13; P = .018).
Twice the risk
The investigators then combined these three independent variables into a weighted TAG score based on a multivariate analysis. Each unit increase in this composite score was associated with increased risk of symptomatic ICH (OR, 1.98; 95% CI, 1.48-2.66; P < .001).
There was no association between patients who received tissue plasminogen activator (tPA) and risk of symptomatic ICH, which Dr. Montalvo Perero said was surprising.
However, “that may be due to a small number” of patients with symptomatic ICH included in the study, she said. “Therefore, that would be an interesting question to ask in future studies with bigger cohorts.”
Larger studies are also needed to validate this scoring system and to test strategies to reduce risk of symptomatic ICH and make thrombectomy safer in patients with elevated TAG scores, Dr. Montalvo Perero said.
A step in the right direction?
Commenting on the study, Jeremy Payne, MD, PhD, director of the Stroke Center at Banner Health’s University Medicine Neuroscience Institute in Phoenix, Arizona, noted the importance of predicting which patients might have secondary bleeding after interventional treatment of a large vessel occlusion stroke
“In aggregate, the role of endovascular thrombectomy is quite clear, but we still struggle to predict at the individual patient level who will benefit,” said Dr. Payne, who was not involved with the research.
Transfer and treatment of these patients also carries an economic cost. “Just getting patients to our center, where about 80% of the complex stroke patients come by helicopter, costs upwards of $30,000,” Dr. Payne said. “The financial argument isn’t one we like to talk much about, but we’re committing to spending probably $100,000-$200,000 on each person’s care.”
This study “attempts to address an important issue,” he said.
Predicting who is more likely to benefit leads to the assumption that if that were to happen, “we could skip all the rigamarole of helicopters and procedures, avoid the extra expense and particularly not make things worse than they already are,” explained Dr. Payne.
Potential limitations include that this is a single-center study and is based on an analysis of 19 patients out of 578. As a result, it is not clear that these findings will necessarily be generalizable to other centers, said Dr. Payne.
The TICI and ASPECTS “are pretty obvious markers of risk,” he noted. “The glucose levels, however, are more subtly interesting.”
He also pointed out that an association between diabetes and worse stroke outcomes is well established.
“The mechanisms are poorly understood, but the role of glucose keeps popping up as a potential marker of risk, and so it’s interesting that it bubbles up in their work too,” Dr. Payne said.
Furthermore, unlike TICI and ASPECTS, glucose levels are modifiable.
“Overall, then, we will continue to study this,” Dr. Payne said. “It’s very important to refine our ability to predict which patients may receive benefit versus harm from such procedures, and this is a step in the right direction.”
Some findings were also published December 2019 in the Journal of Neurology, Neurosurgery & Psychiatry.
Montalvo Perero and Payne have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
SOURCE: Motalvo Perero MJ et al. AAN 2020, Abstract S20.001.
(ICH), new research suggests. In a study of nearly 600 patients undergoing thrombectomy, investigators combined a modified Thrombolysis in Cerebral Ischemia (TICI) score, an Alberta Stroke Program Early Computed Tomography Score (ASPECTS), and glucose levels (the “TAG score”) to predict risk. Results showed that each unit increase in the combination score was associated with a significant, nearly twofold greater likelihood of symptomatic ICH.
“It is very easy” to calculate the new score in a clinical setting, lead author Mayra Johana Montalvo Perero, MD, Department of Neurology, Brown University and Rhode Island Hospital, Providence, said. “You just need three variables.”
The findings were presented online as part of the 2020 American Academy of Neurology Science Highlights.
Limited data
High TAG scores are associated with symptomatic ICH in patients receiving mechanical thrombectomy, Dr. Montalvo Perero and colleagues said.
Although clinical predictors of symptomatic ICH are well established, “there is limited data in patients who underwent mechanical thrombectomy,” the researchers noted.
To learn more, they assessed 578 patients (52% women; mean age, 73 years) who had mechanical thrombectomy for acute ischemic stroke at a comprehensive stroke center. Within this cohort, 19 patients (3.3%) developed symptomatic ICH.
The investigators compared clinical and radiographic findings between patients who experienced symptomatic ICH and those who did not.
The TICI score emerged as a predictor when each unit decrease in this score was associated with greater risk for symptomatic ICH (odds ratio, 5.13; 95% confidence interval, 1.84-14.29; P = .002).
Each one-point decrease in the ASPECTS score also predicted increased risk (OR, 1.52; 95% CI, 1.1-2.0; P = .003).
“The main driver is the size of the stroke core, which is correlated with the ASPECTS score,” Dr. Montalvo Perero said.
Each 10 mg/dL increase in glucose level also correlated with increased risk (OR, 1.07; 95% CI, 1.01-1.13; P = .018).
Twice the risk
The investigators then combined these three independent variables into a weighted TAG score based on a multivariate analysis. Each unit increase in this composite score was associated with increased risk of symptomatic ICH (OR, 1.98; 95% CI, 1.48-2.66; P < .001).
There was no association between patients who received tissue plasminogen activator (tPA) and risk of symptomatic ICH, which Dr. Montalvo Perero said was surprising.
However, “that may be due to a small number” of patients with symptomatic ICH included in the study, she said. “Therefore, that would be an interesting question to ask in future studies with bigger cohorts.”
Larger studies are also needed to validate this scoring system and to test strategies to reduce risk of symptomatic ICH and make thrombectomy safer in patients with elevated TAG scores, Dr. Montalvo Perero said.
A step in the right direction?
Commenting on the study, Jeremy Payne, MD, PhD, director of the Stroke Center at Banner Health’s University Medicine Neuroscience Institute in Phoenix, Arizona, noted the importance of predicting which patients might have secondary bleeding after interventional treatment of a large vessel occlusion stroke
“In aggregate, the role of endovascular thrombectomy is quite clear, but we still struggle to predict at the individual patient level who will benefit,” said Dr. Payne, who was not involved with the research.
Transfer and treatment of these patients also carries an economic cost. “Just getting patients to our center, where about 80% of the complex stroke patients come by helicopter, costs upwards of $30,000,” Dr. Payne said. “The financial argument isn’t one we like to talk much about, but we’re committing to spending probably $100,000-$200,000 on each person’s care.”
This study “attempts to address an important issue,” he said.
Predicting who is more likely to benefit leads to the assumption that if that were to happen, “we could skip all the rigamarole of helicopters and procedures, avoid the extra expense and particularly not make things worse than they already are,” explained Dr. Payne.
Potential limitations include that this is a single-center study and is based on an analysis of 19 patients out of 578. As a result, it is not clear that these findings will necessarily be generalizable to other centers, said Dr. Payne.
The TICI and ASPECTS “are pretty obvious markers of risk,” he noted. “The glucose levels, however, are more subtly interesting.”
He also pointed out that an association between diabetes and worse stroke outcomes is well established.
“The mechanisms are poorly understood, but the role of glucose keeps popping up as a potential marker of risk, and so it’s interesting that it bubbles up in their work too,” Dr. Payne said.
Furthermore, unlike TICI and ASPECTS, glucose levels are modifiable.
“Overall, then, we will continue to study this,” Dr. Payne said. “It’s very important to refine our ability to predict which patients may receive benefit versus harm from such procedures, and this is a step in the right direction.”
Some findings were also published December 2019 in the Journal of Neurology, Neurosurgery & Psychiatry.
Montalvo Perero and Payne have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
SOURCE: Motalvo Perero MJ et al. AAN 2020, Abstract S20.001.
AAN 2020
COVID-19: Are acute stroke patients avoiding emergency care?
(EDs).
Stroke specialists in New Orleans, Chicago, Seattle, and elsewhere told Medscape Medical News they are seeing a precipitous drop in the number of acute strokes at their institutions – and not just in the number of milder cases. Doctors on Twitter are sharing similar reports and are using social media to highlight this issue.
Gabriel Vidal, MD, a vascular and interventional neurologist at the Ochsner Medical Center, New Orleans, Louisiana, said there are “definitely” fewer patients with stroke and transient ischemic attack (TIA) seeking care at his facility and others throughout the New Orleans area, which has been hard hit by COVID-19.
“Even in Louisiana, we have a very large 53-hospital telestroke network, and the number of consults has diminished greatly,” Vidal added.
In Chicago, emergency medical service activations for patients with suspected strokes are down about 30%, Shyam Prabhakaran, MD, professor and chair of neurology at the University of Chicago Biological Sciences, Illinois, told Medscape Medical News.
“It appears to be that mild stroke and TIA patients may be more likely to stay at home and seek alternative care rather than come to the ED,” Prabhakaran said. However, “the severe strokes may be less affected and continue to come to emergency departments.”
“Getting the Word Out”
That may not be the whole story in Seattle, Washington, where a stroke specialist at Harborview Medical Center reported a drop in patients across the stroke-severity spectrum.
Some patients with milder strokes no longer come to Harborview for a comprehensive evaluation and workup, but that is only “a partial explanation,” said David Tirschwell, MD, medical director of comprehensive stroke care at the University of Washington (UW) Medicine Stroke Center at Harborview and a professor of neurology at UW.
“The thrombectomies are down also,” he added. “It’s hard to have great numbers in real time, but it’s probably safe to say it’s at least a 50% reduction in the number of admissions.”
As a stroke referral center, his institution is seeing fewer local cases and referrals from outside hospitals. “I think both of those sources for admissions of stroke cases are down,” Tirschwell said.
Recognizing the seriousness of forgoing essential care for acute stroke, neurologists, institutions, and medical groups are taking to social media to potentially save lives.
“Across our @FLStrokeReg we are seeing less patients with #stroke symptoms coming to our hospitals. We need to get the word out that our teams are working hard to safely provide care when needed during #COVID19,” tweeted Ralph Sacco, MD, chief and professor of neurology, University of Miami Miller School of Medicine in South Florida.
Although Florida Stroke Registry data are not publicly available, anecdotal reports suggest that stroke admissions are down among many hospitals, Sacco told Medscape Medical News.
Furthermore, this is not a phenomenon only in the United States. “This has also been reported in other nations hit by COVID-19,” he said.
China is a prime example. There, many stroke centers have shown reduced functioning “because of fear of in-hospital cross infection and lack of experienced stroke care experts,” Jing Zhao, MD, PhD, and colleagues write in an editorial published online March 31 in Stroke.
Preliminary data show that “thrombectomies in Shanghai decreased by 50% in the first month after the Spring Festival compared with the same period in 2019,” write the editorialists, who are from Kings College London and the University of Pennsylvania in Philadelphia.
“Although the control of the COVID-19 is very important, at the same time, the management of stroke must not be neglected,” they add.
“Over 9000 new stroke cases occur each day in China alone. It cannot be right that treatment for one potentially curable disease is euthanized at the expense of another.”
Fear Factor?
The reasons individuals who may have experienced a stroke are avoiding emergency care is unclear at the moment. “I’m not really sure anyone really understands why, quite honestly,” Tirschwell said.
Until survey data or other data emerge, many experts are assuming that fear of COVID-19 is trumping other medical concerns, including emergency treatment of stroke.
“We believe this could represent patients being fearful to come to medical facilities with stroke-like symptoms, given the COVID-19 pandemic,” said Sacco, who is also incoming editor-in-chief of Stroke.
The BBC has been getting the word out in the United Kingdom via social media, with a tweet to “Dial 999 for stroke emergencies despite coronavirus.”
The World Stroke Campaign is also using Twitter to emphasize the need for urgent stroke care when appropriate:
“Don’t let concerns about COVID19 prevent you from seeking emergency treatment for stroke. If you spot the signs of stroke act FAST. Get emergency medical assistance,” the group urged in a tweet.
Don’t Hesitate
The American Heart Association (AHA) has addressed this troubling trend as well.
“People with serious symptoms shouldn’t ignore them,” Sarah Perlman, MD, associate professor of emergency medicine at the University of Colorado School of Medicine, Denver, states in an article on the AHA website.
Perlman added that some individuals who have signs of stroke and heart disease may hesitate to seek care because of fear that they are adding to an overburdened healthcare staff and system. However, she dismissed those concerns outright.
“If you’re experiencing warning signs of a heart attack or stroke, call 911,” she said. “Clearly, if there’s an emergency, we are available and capable and eager to take care of you.”
This article first appeared on Medscape.com.
(EDs).
Stroke specialists in New Orleans, Chicago, Seattle, and elsewhere told Medscape Medical News they are seeing a precipitous drop in the number of acute strokes at their institutions – and not just in the number of milder cases. Doctors on Twitter are sharing similar reports and are using social media to highlight this issue.
Gabriel Vidal, MD, a vascular and interventional neurologist at the Ochsner Medical Center, New Orleans, Louisiana, said there are “definitely” fewer patients with stroke and transient ischemic attack (TIA) seeking care at his facility and others throughout the New Orleans area, which has been hard hit by COVID-19.
“Even in Louisiana, we have a very large 53-hospital telestroke network, and the number of consults has diminished greatly,” Vidal added.
In Chicago, emergency medical service activations for patients with suspected strokes are down about 30%, Shyam Prabhakaran, MD, professor and chair of neurology at the University of Chicago Biological Sciences, Illinois, told Medscape Medical News.
“It appears to be that mild stroke and TIA patients may be more likely to stay at home and seek alternative care rather than come to the ED,” Prabhakaran said. However, “the severe strokes may be less affected and continue to come to emergency departments.”
“Getting the Word Out”
That may not be the whole story in Seattle, Washington, where a stroke specialist at Harborview Medical Center reported a drop in patients across the stroke-severity spectrum.
Some patients with milder strokes no longer come to Harborview for a comprehensive evaluation and workup, but that is only “a partial explanation,” said David Tirschwell, MD, medical director of comprehensive stroke care at the University of Washington (UW) Medicine Stroke Center at Harborview and a professor of neurology at UW.
“The thrombectomies are down also,” he added. “It’s hard to have great numbers in real time, but it’s probably safe to say it’s at least a 50% reduction in the number of admissions.”
As a stroke referral center, his institution is seeing fewer local cases and referrals from outside hospitals. “I think both of those sources for admissions of stroke cases are down,” Tirschwell said.
Recognizing the seriousness of forgoing essential care for acute stroke, neurologists, institutions, and medical groups are taking to social media to potentially save lives.
“Across our @FLStrokeReg we are seeing less patients with #stroke symptoms coming to our hospitals. We need to get the word out that our teams are working hard to safely provide care when needed during #COVID19,” tweeted Ralph Sacco, MD, chief and professor of neurology, University of Miami Miller School of Medicine in South Florida.
Although Florida Stroke Registry data are not publicly available, anecdotal reports suggest that stroke admissions are down among many hospitals, Sacco told Medscape Medical News.
Furthermore, this is not a phenomenon only in the United States. “This has also been reported in other nations hit by COVID-19,” he said.
China is a prime example. There, many stroke centers have shown reduced functioning “because of fear of in-hospital cross infection and lack of experienced stroke care experts,” Jing Zhao, MD, PhD, and colleagues write in an editorial published online March 31 in Stroke.
Preliminary data show that “thrombectomies in Shanghai decreased by 50% in the first month after the Spring Festival compared with the same period in 2019,” write the editorialists, who are from Kings College London and the University of Pennsylvania in Philadelphia.
“Although the control of the COVID-19 is very important, at the same time, the management of stroke must not be neglected,” they add.
“Over 9000 new stroke cases occur each day in China alone. It cannot be right that treatment for one potentially curable disease is euthanized at the expense of another.”
Fear Factor?
The reasons individuals who may have experienced a stroke are avoiding emergency care is unclear at the moment. “I’m not really sure anyone really understands why, quite honestly,” Tirschwell said.
Until survey data or other data emerge, many experts are assuming that fear of COVID-19 is trumping other medical concerns, including emergency treatment of stroke.
“We believe this could represent patients being fearful to come to medical facilities with stroke-like symptoms, given the COVID-19 pandemic,” said Sacco, who is also incoming editor-in-chief of Stroke.
The BBC has been getting the word out in the United Kingdom via social media, with a tweet to “Dial 999 for stroke emergencies despite coronavirus.”
The World Stroke Campaign is also using Twitter to emphasize the need for urgent stroke care when appropriate:
“Don’t let concerns about COVID19 prevent you from seeking emergency treatment for stroke. If you spot the signs of stroke act FAST. Get emergency medical assistance,” the group urged in a tweet.
Don’t Hesitate
The American Heart Association (AHA) has addressed this troubling trend as well.
“People with serious symptoms shouldn’t ignore them,” Sarah Perlman, MD, associate professor of emergency medicine at the University of Colorado School of Medicine, Denver, states in an article on the AHA website.
Perlman added that some individuals who have signs of stroke and heart disease may hesitate to seek care because of fear that they are adding to an overburdened healthcare staff and system. However, she dismissed those concerns outright.
“If you’re experiencing warning signs of a heart attack or stroke, call 911,” she said. “Clearly, if there’s an emergency, we are available and capable and eager to take care of you.”
This article first appeared on Medscape.com.
(EDs).
Stroke specialists in New Orleans, Chicago, Seattle, and elsewhere told Medscape Medical News they are seeing a precipitous drop in the number of acute strokes at their institutions – and not just in the number of milder cases. Doctors on Twitter are sharing similar reports and are using social media to highlight this issue.
Gabriel Vidal, MD, a vascular and interventional neurologist at the Ochsner Medical Center, New Orleans, Louisiana, said there are “definitely” fewer patients with stroke and transient ischemic attack (TIA) seeking care at his facility and others throughout the New Orleans area, which has been hard hit by COVID-19.
“Even in Louisiana, we have a very large 53-hospital telestroke network, and the number of consults has diminished greatly,” Vidal added.
In Chicago, emergency medical service activations for patients with suspected strokes are down about 30%, Shyam Prabhakaran, MD, professor and chair of neurology at the University of Chicago Biological Sciences, Illinois, told Medscape Medical News.
“It appears to be that mild stroke and TIA patients may be more likely to stay at home and seek alternative care rather than come to the ED,” Prabhakaran said. However, “the severe strokes may be less affected and continue to come to emergency departments.”
“Getting the Word Out”
That may not be the whole story in Seattle, Washington, where a stroke specialist at Harborview Medical Center reported a drop in patients across the stroke-severity spectrum.
Some patients with milder strokes no longer come to Harborview for a comprehensive evaluation and workup, but that is only “a partial explanation,” said David Tirschwell, MD, medical director of comprehensive stroke care at the University of Washington (UW) Medicine Stroke Center at Harborview and a professor of neurology at UW.
“The thrombectomies are down also,” he added. “It’s hard to have great numbers in real time, but it’s probably safe to say it’s at least a 50% reduction in the number of admissions.”
As a stroke referral center, his institution is seeing fewer local cases and referrals from outside hospitals. “I think both of those sources for admissions of stroke cases are down,” Tirschwell said.
Recognizing the seriousness of forgoing essential care for acute stroke, neurologists, institutions, and medical groups are taking to social media to potentially save lives.
“Across our @FLStrokeReg we are seeing less patients with #stroke symptoms coming to our hospitals. We need to get the word out that our teams are working hard to safely provide care when needed during #COVID19,” tweeted Ralph Sacco, MD, chief and professor of neurology, University of Miami Miller School of Medicine in South Florida.
Although Florida Stroke Registry data are not publicly available, anecdotal reports suggest that stroke admissions are down among many hospitals, Sacco told Medscape Medical News.
Furthermore, this is not a phenomenon only in the United States. “This has also been reported in other nations hit by COVID-19,” he said.
China is a prime example. There, many stroke centers have shown reduced functioning “because of fear of in-hospital cross infection and lack of experienced stroke care experts,” Jing Zhao, MD, PhD, and colleagues write in an editorial published online March 31 in Stroke.
Preliminary data show that “thrombectomies in Shanghai decreased by 50% in the first month after the Spring Festival compared with the same period in 2019,” write the editorialists, who are from Kings College London and the University of Pennsylvania in Philadelphia.
“Although the control of the COVID-19 is very important, at the same time, the management of stroke must not be neglected,” they add.
“Over 9000 new stroke cases occur each day in China alone. It cannot be right that treatment for one potentially curable disease is euthanized at the expense of another.”
Fear Factor?
The reasons individuals who may have experienced a stroke are avoiding emergency care is unclear at the moment. “I’m not really sure anyone really understands why, quite honestly,” Tirschwell said.
Until survey data or other data emerge, many experts are assuming that fear of COVID-19 is trumping other medical concerns, including emergency treatment of stroke.
“We believe this could represent patients being fearful to come to medical facilities with stroke-like symptoms, given the COVID-19 pandemic,” said Sacco, who is also incoming editor-in-chief of Stroke.
The BBC has been getting the word out in the United Kingdom via social media, with a tweet to “Dial 999 for stroke emergencies despite coronavirus.”
The World Stroke Campaign is also using Twitter to emphasize the need for urgent stroke care when appropriate:
“Don’t let concerns about COVID19 prevent you from seeking emergency treatment for stroke. If you spot the signs of stroke act FAST. Get emergency medical assistance,” the group urged in a tweet.
Don’t Hesitate
The American Heart Association (AHA) has addressed this troubling trend as well.
“People with serious symptoms shouldn’t ignore them,” Sarah Perlman, MD, associate professor of emergency medicine at the University of Colorado School of Medicine, Denver, states in an article on the AHA website.
Perlman added that some individuals who have signs of stroke and heart disease may hesitate to seek care because of fear that they are adding to an overburdened healthcare staff and system. However, she dismissed those concerns outright.
“If you’re experiencing warning signs of a heart attack or stroke, call 911,” she said. “Clearly, if there’s an emergency, we are available and capable and eager to take care of you.”
This article first appeared on Medscape.com.
National Watchman registry reports impressive procedural safety
Early results from the massive National Cardiovascular Data Registry Left Atrial Appendage Occlusion Registry indicate that the rollout of the Watchman device into routine clinical practice is going smoothly, with a higher implant success rate and a substantially lower in-hospital complication rate than that seen in the pivotal randomized clinical trials, James V. Freeman, MD, reported at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. The meeting was conducted online after its cancellation because of the COVID-19 pandemic.
These real-world results are particularly impressive because the 38,158 registry participants were on average significantly older and sicker than were patients in the clinical trials. They were at higher risk of both stroke and bleeding, yet they fared better in terms of procedural safety, observed Dr. Freeman, an electrophysiologist and director of the Yale University Atrial Fibrillation Center in New Haven, Conn.
“You always worry that once you get outside of the clinical trials setting and you roll out to a large number of centers, including some that are relatively low volume, that you’re going to start to see higher rates of complications. And overall, broadly speaking, the rates of adverse events were quite reassuring,” he said.
The registry, maintained by the ACC, serves as the postmarketing surveillance tool mandated by the Food and Drug Administration and Centers for Medicare & Medicaid Services. The 38,158 participants make this registry the world’s largest patient experience with the Watchman device by many orders of magnitude. Dr. Freeman’s report included patients enrolled during 2016-2018 who were treated at 495 hospitals by 1,318 physician interventionalists. CMS reimbursement requires participation in the registry, which captures more than 95% of all Watchman procedures done in the United States. Although Dr. Freeman presented only the acute in-hospital outcomes, active follow-up for adverse events and medical therapy will be conducted at 45 days, 6 months, and 1 and 2 years.
Participants in the Left Atrial Appendage Occlusion (LAAO) Registry averaged 76.1 years of age, which is 2-4 years older than patients in the pivotal PROTECT-AF and PREVAIL trials or the 1,025-patient EWOLUTION registry. The LAAO Registry participants had a mean CHA2DS2-VASc score of 4.6, compared with 3.4 in PROTECT-AF and 3.8 in PREVAIL. Their mean HAS BLED score was 3.0. Thirty percent had a prior ischemic stroke or transient ischemic attack, 12% had a prior intracranial hemorrhage, and 69% had a history of clinically relevant bleeding. Thirty percent had heart failure, 92% were hypertensive, and 30% had diabetes.
“The take home here is that these patients were at moderate to high risk of stroke and they also carried a high risk of bleeding and therefore had some relative contraindication to anticoagulation,” according to the cardiologist. “The patient population overall is really in accordance with the CMS guidance. We’re not seeing a lot of patients who are getting this device for a lifestyle indication. Most of these patients are really stuck between a rock and a hard place.”
Most hospitals offering the Watchman did 10-40 cases per year. The median annual physician volume was 12 cases. However, there was substantial variation in both hospital and physician volumes.
The device was deployed in 93% of procedures attempted; roughly half of cancellations were cause by LAAO thrombus detected on the day of the procedure. The acute procedural success rate when the device was deployed was 98.3%, compared with 90.9% in PROTECT-AF and 95.1% in PREVAIL. The rate of device margin residual leak of 5 mm or more among registry participants with an acutely successful procedure was 0.2%.
The rate of any major in-hospital complication in the LAAO Registry was 2.16%, the most common of which was pericardial effusion requiring intervention, which occurred in 1.39% of cases. The major bleeding rate was 1.25%. The stroke/transient ischemic attack rate was 0.17%. Systemic arterial embolism was a rare event, occurring in less than 0.01% of patients, as was acute MI, with an incidence of 0.04%. Device embolization occurred in 0.07% of patients.
By comparison, the 7-day rate of pericardial effusion requiring intervention was 4.0% in PROTECT-AF and 1.9% in PREVAIL, with procedure-related stroke rates of 1.1% and 0.7%, respectively, and device embolization rates of 0.4% and 0.7%. The major bleeding rate in PROTECT-AF was 3.5%, nearly triple that in the real-world registry.
Discussant Mark A. Estes, MD, characterized the acute outcomes in the LAAO Registry as “an improvement – a considerable improvement – over some of the early data in PREVAIL and PROTECT-AF.” He credited this to the “very robust validation procedure” the Watchman closure device has undergone, which included the clinical trials, regulatory requirements for training and patient selection, and mandatory reporting of outcomes in the registry.
He noted that a lot is happening now with the Watchman device. There are a couple of dozen prospective clinical trials, including one on the Watchman versus direct oral anticoagulant (DOAC) therapy and another on left atrial ablation plus left atrial appendage closure versus a DOAC. A new-generation Watchman device, the Watchman FLX, is approved in Europe and undergoing an ongoing FDA-mandated approval trial in the United States.
“It has a lot of technical advantages,” according to Dr. Estes, an electrophysiologist and professor of medicine at the University of Pittsburgh.
Current guidelines give LAAO a class IIb rating, meaning it “could be considered” in patients with atrial fibrillation at increased risk of stroke who have a contraindication to long-term anticoagulation. Dr. Estes asked: Does the LAAO Registry data warrant a rating upgrade to a stronger recommendation?
Dr. Freeman replied that the new data should allay the guideline writers’ and government regulators’ concerns regarding acute procedural safety. But that’s only part of the picture. He and his coinvestigators are busy gathering data on intermediate-term outcomes, analyzing the impact of various strategies for periprocedural and long-term management of antiplatelet and anticoagulant medications with an eye toward identifying best practices, and investigating the relationship between procedural volume and outcomes, information, which could have an impact on the next iteration of the guidelines.
Simultaneous with his presentation at ACC 2020, the study was published online (J Am Coll Cardiol. 2020 Mar 13;75[13]1503-18).
In an accompanying editorial, Dhanunjaya Lakkireddy, MD, commented that an important contribution of the LAAO Registry is its inclusion of an enormous number of patients with contraindications to oral anticoagulation, a population excluded from the PROTECT-AF and PREVAIL randomized trials.
The short-term results of the registry suggest a relaxation of the current strict requirement for surgical backup during Watchman procedures is in order, added Dr. Lakkireddy, professor of medicine at the University of Missouri, Columbia, and medical director of the Kansas City Heart Rhythm Institute (J Am Coll Cardiol. 2020 Mar 13;75[13]:1519-22).
Dr. Freeman reported serving as a consultant to Boston Scientific, which markets the Watchman, as well as to Medtronic, Janssen, and Biosense Webster.
SOURCE: Freeman JF. ACC 2020, Abstract 409-10.
Early results from the massive National Cardiovascular Data Registry Left Atrial Appendage Occlusion Registry indicate that the rollout of the Watchman device into routine clinical practice is going smoothly, with a higher implant success rate and a substantially lower in-hospital complication rate than that seen in the pivotal randomized clinical trials, James V. Freeman, MD, reported at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. The meeting was conducted online after its cancellation because of the COVID-19 pandemic.
These real-world results are particularly impressive because the 38,158 registry participants were on average significantly older and sicker than were patients in the clinical trials. They were at higher risk of both stroke and bleeding, yet they fared better in terms of procedural safety, observed Dr. Freeman, an electrophysiologist and director of the Yale University Atrial Fibrillation Center in New Haven, Conn.
“You always worry that once you get outside of the clinical trials setting and you roll out to a large number of centers, including some that are relatively low volume, that you’re going to start to see higher rates of complications. And overall, broadly speaking, the rates of adverse events were quite reassuring,” he said.
The registry, maintained by the ACC, serves as the postmarketing surveillance tool mandated by the Food and Drug Administration and Centers for Medicare & Medicaid Services. The 38,158 participants make this registry the world’s largest patient experience with the Watchman device by many orders of magnitude. Dr. Freeman’s report included patients enrolled during 2016-2018 who were treated at 495 hospitals by 1,318 physician interventionalists. CMS reimbursement requires participation in the registry, which captures more than 95% of all Watchman procedures done in the United States. Although Dr. Freeman presented only the acute in-hospital outcomes, active follow-up for adverse events and medical therapy will be conducted at 45 days, 6 months, and 1 and 2 years.
Participants in the Left Atrial Appendage Occlusion (LAAO) Registry averaged 76.1 years of age, which is 2-4 years older than patients in the pivotal PROTECT-AF and PREVAIL trials or the 1,025-patient EWOLUTION registry. The LAAO Registry participants had a mean CHA2DS2-VASc score of 4.6, compared with 3.4 in PROTECT-AF and 3.8 in PREVAIL. Their mean HAS BLED score was 3.0. Thirty percent had a prior ischemic stroke or transient ischemic attack, 12% had a prior intracranial hemorrhage, and 69% had a history of clinically relevant bleeding. Thirty percent had heart failure, 92% were hypertensive, and 30% had diabetes.
“The take home here is that these patients were at moderate to high risk of stroke and they also carried a high risk of bleeding and therefore had some relative contraindication to anticoagulation,” according to the cardiologist. “The patient population overall is really in accordance with the CMS guidance. We’re not seeing a lot of patients who are getting this device for a lifestyle indication. Most of these patients are really stuck between a rock and a hard place.”
Most hospitals offering the Watchman did 10-40 cases per year. The median annual physician volume was 12 cases. However, there was substantial variation in both hospital and physician volumes.
The device was deployed in 93% of procedures attempted; roughly half of cancellations were cause by LAAO thrombus detected on the day of the procedure. The acute procedural success rate when the device was deployed was 98.3%, compared with 90.9% in PROTECT-AF and 95.1% in PREVAIL. The rate of device margin residual leak of 5 mm or more among registry participants with an acutely successful procedure was 0.2%.
The rate of any major in-hospital complication in the LAAO Registry was 2.16%, the most common of which was pericardial effusion requiring intervention, which occurred in 1.39% of cases. The major bleeding rate was 1.25%. The stroke/transient ischemic attack rate was 0.17%. Systemic arterial embolism was a rare event, occurring in less than 0.01% of patients, as was acute MI, with an incidence of 0.04%. Device embolization occurred in 0.07% of patients.
By comparison, the 7-day rate of pericardial effusion requiring intervention was 4.0% in PROTECT-AF and 1.9% in PREVAIL, with procedure-related stroke rates of 1.1% and 0.7%, respectively, and device embolization rates of 0.4% and 0.7%. The major bleeding rate in PROTECT-AF was 3.5%, nearly triple that in the real-world registry.
Discussant Mark A. Estes, MD, characterized the acute outcomes in the LAAO Registry as “an improvement – a considerable improvement – over some of the early data in PREVAIL and PROTECT-AF.” He credited this to the “very robust validation procedure” the Watchman closure device has undergone, which included the clinical trials, regulatory requirements for training and patient selection, and mandatory reporting of outcomes in the registry.
He noted that a lot is happening now with the Watchman device. There are a couple of dozen prospective clinical trials, including one on the Watchman versus direct oral anticoagulant (DOAC) therapy and another on left atrial ablation plus left atrial appendage closure versus a DOAC. A new-generation Watchman device, the Watchman FLX, is approved in Europe and undergoing an ongoing FDA-mandated approval trial in the United States.
“It has a lot of technical advantages,” according to Dr. Estes, an electrophysiologist and professor of medicine at the University of Pittsburgh.
Current guidelines give LAAO a class IIb rating, meaning it “could be considered” in patients with atrial fibrillation at increased risk of stroke who have a contraindication to long-term anticoagulation. Dr. Estes asked: Does the LAAO Registry data warrant a rating upgrade to a stronger recommendation?
Dr. Freeman replied that the new data should allay the guideline writers’ and government regulators’ concerns regarding acute procedural safety. But that’s only part of the picture. He and his coinvestigators are busy gathering data on intermediate-term outcomes, analyzing the impact of various strategies for periprocedural and long-term management of antiplatelet and anticoagulant medications with an eye toward identifying best practices, and investigating the relationship between procedural volume and outcomes, information, which could have an impact on the next iteration of the guidelines.
Simultaneous with his presentation at ACC 2020, the study was published online (J Am Coll Cardiol. 2020 Mar 13;75[13]1503-18).
In an accompanying editorial, Dhanunjaya Lakkireddy, MD, commented that an important contribution of the LAAO Registry is its inclusion of an enormous number of patients with contraindications to oral anticoagulation, a population excluded from the PROTECT-AF and PREVAIL randomized trials.
The short-term results of the registry suggest a relaxation of the current strict requirement for surgical backup during Watchman procedures is in order, added Dr. Lakkireddy, professor of medicine at the University of Missouri, Columbia, and medical director of the Kansas City Heart Rhythm Institute (J Am Coll Cardiol. 2020 Mar 13;75[13]:1519-22).
Dr. Freeman reported serving as a consultant to Boston Scientific, which markets the Watchman, as well as to Medtronic, Janssen, and Biosense Webster.
SOURCE: Freeman JF. ACC 2020, Abstract 409-10.
Early results from the massive National Cardiovascular Data Registry Left Atrial Appendage Occlusion Registry indicate that the rollout of the Watchman device into routine clinical practice is going smoothly, with a higher implant success rate and a substantially lower in-hospital complication rate than that seen in the pivotal randomized clinical trials, James V. Freeman, MD, reported at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. The meeting was conducted online after its cancellation because of the COVID-19 pandemic.
These real-world results are particularly impressive because the 38,158 registry participants were on average significantly older and sicker than were patients in the clinical trials. They were at higher risk of both stroke and bleeding, yet they fared better in terms of procedural safety, observed Dr. Freeman, an electrophysiologist and director of the Yale University Atrial Fibrillation Center in New Haven, Conn.
“You always worry that once you get outside of the clinical trials setting and you roll out to a large number of centers, including some that are relatively low volume, that you’re going to start to see higher rates of complications. And overall, broadly speaking, the rates of adverse events were quite reassuring,” he said.
The registry, maintained by the ACC, serves as the postmarketing surveillance tool mandated by the Food and Drug Administration and Centers for Medicare & Medicaid Services. The 38,158 participants make this registry the world’s largest patient experience with the Watchman device by many orders of magnitude. Dr. Freeman’s report included patients enrolled during 2016-2018 who were treated at 495 hospitals by 1,318 physician interventionalists. CMS reimbursement requires participation in the registry, which captures more than 95% of all Watchman procedures done in the United States. Although Dr. Freeman presented only the acute in-hospital outcomes, active follow-up for adverse events and medical therapy will be conducted at 45 days, 6 months, and 1 and 2 years.
Participants in the Left Atrial Appendage Occlusion (LAAO) Registry averaged 76.1 years of age, which is 2-4 years older than patients in the pivotal PROTECT-AF and PREVAIL trials or the 1,025-patient EWOLUTION registry. The LAAO Registry participants had a mean CHA2DS2-VASc score of 4.6, compared with 3.4 in PROTECT-AF and 3.8 in PREVAIL. Their mean HAS BLED score was 3.0. Thirty percent had a prior ischemic stroke or transient ischemic attack, 12% had a prior intracranial hemorrhage, and 69% had a history of clinically relevant bleeding. Thirty percent had heart failure, 92% were hypertensive, and 30% had diabetes.
“The take home here is that these patients were at moderate to high risk of stroke and they also carried a high risk of bleeding and therefore had some relative contraindication to anticoagulation,” according to the cardiologist. “The patient population overall is really in accordance with the CMS guidance. We’re not seeing a lot of patients who are getting this device for a lifestyle indication. Most of these patients are really stuck between a rock and a hard place.”
Most hospitals offering the Watchman did 10-40 cases per year. The median annual physician volume was 12 cases. However, there was substantial variation in both hospital and physician volumes.
The device was deployed in 93% of procedures attempted; roughly half of cancellations were cause by LAAO thrombus detected on the day of the procedure. The acute procedural success rate when the device was deployed was 98.3%, compared with 90.9% in PROTECT-AF and 95.1% in PREVAIL. The rate of device margin residual leak of 5 mm or more among registry participants with an acutely successful procedure was 0.2%.
The rate of any major in-hospital complication in the LAAO Registry was 2.16%, the most common of which was pericardial effusion requiring intervention, which occurred in 1.39% of cases. The major bleeding rate was 1.25%. The stroke/transient ischemic attack rate was 0.17%. Systemic arterial embolism was a rare event, occurring in less than 0.01% of patients, as was acute MI, with an incidence of 0.04%. Device embolization occurred in 0.07% of patients.
By comparison, the 7-day rate of pericardial effusion requiring intervention was 4.0% in PROTECT-AF and 1.9% in PREVAIL, with procedure-related stroke rates of 1.1% and 0.7%, respectively, and device embolization rates of 0.4% and 0.7%. The major bleeding rate in PROTECT-AF was 3.5%, nearly triple that in the real-world registry.
Discussant Mark A. Estes, MD, characterized the acute outcomes in the LAAO Registry as “an improvement – a considerable improvement – over some of the early data in PREVAIL and PROTECT-AF.” He credited this to the “very robust validation procedure” the Watchman closure device has undergone, which included the clinical trials, regulatory requirements for training and patient selection, and mandatory reporting of outcomes in the registry.
He noted that a lot is happening now with the Watchman device. There are a couple of dozen prospective clinical trials, including one on the Watchman versus direct oral anticoagulant (DOAC) therapy and another on left atrial ablation plus left atrial appendage closure versus a DOAC. A new-generation Watchman device, the Watchman FLX, is approved in Europe and undergoing an ongoing FDA-mandated approval trial in the United States.
“It has a lot of technical advantages,” according to Dr. Estes, an electrophysiologist and professor of medicine at the University of Pittsburgh.
Current guidelines give LAAO a class IIb rating, meaning it “could be considered” in patients with atrial fibrillation at increased risk of stroke who have a contraindication to long-term anticoagulation. Dr. Estes asked: Does the LAAO Registry data warrant a rating upgrade to a stronger recommendation?
Dr. Freeman replied that the new data should allay the guideline writers’ and government regulators’ concerns regarding acute procedural safety. But that’s only part of the picture. He and his coinvestigators are busy gathering data on intermediate-term outcomes, analyzing the impact of various strategies for periprocedural and long-term management of antiplatelet and anticoagulant medications with an eye toward identifying best practices, and investigating the relationship between procedural volume and outcomes, information, which could have an impact on the next iteration of the guidelines.
Simultaneous with his presentation at ACC 2020, the study was published online (J Am Coll Cardiol. 2020 Mar 13;75[13]1503-18).
In an accompanying editorial, Dhanunjaya Lakkireddy, MD, commented that an important contribution of the LAAO Registry is its inclusion of an enormous number of patients with contraindications to oral anticoagulation, a population excluded from the PROTECT-AF and PREVAIL randomized trials.
The short-term results of the registry suggest a relaxation of the current strict requirement for surgical backup during Watchman procedures is in order, added Dr. Lakkireddy, professor of medicine at the University of Missouri, Columbia, and medical director of the Kansas City Heart Rhythm Institute (J Am Coll Cardiol. 2020 Mar 13;75[13]:1519-22).
Dr. Freeman reported serving as a consultant to Boston Scientific, which markets the Watchman, as well as to Medtronic, Janssen, and Biosense Webster.
SOURCE: Freeman JF. ACC 2020, Abstract 409-10.
FROM ACC 2020
Cardiovascular disease is implicated in link between air pollution and dementia
Virtually all of the association between air pollution and dementia seemed to occur through the presence or the development of cardiovascular disease, which suggests a need to optimize treatment of concurrent cardiovascular disease and risk-factor control in older adults at higher risk for dementia and living in polluted urban areas, said lead author Giulia Grande, MD, a researcher at the Aging Research Center, Karolinska Institutet and Stockholm University, in Solna, Sweden.
In the longitudinal, population-based cohort study, investigators studied 2,927 randomly selected residents in a district of Stockholm who were aged 60 years or older (mean, 74.1 years), lived at home or in institutions, and were free of dementia at baseline (March 2001 through August 2004).
The investigators assessed the participants’ exposure to two major air pollutants – particulate matter ≤2.5 mcm and nitrogen oxide – yearly starting in 1990, from outdoor levels at their residential addresses. Both pollutants are generated by road traffic, among other sources.
Results reported in JAMA Neurology showed that, with a mean follow-up of 6.01 years, 12.4% of the older adults received a dementia diagnosis.
Dementia risk increased with the level of air pollutants at their residential address in the past, with strongest associations seen for exposure in the preceding 5 years: The hazard ratio (HR) for dementia was 1.54 for an interquartile range difference of 0.88 mcg/m3 in particulate matter ≤2.5 mcm and 1.14 for an interquartile range difference of 8.35 mcg/m3 in nitrogen oxide during that time period.
Of note, the study cohort lived in an area having “comparatively good ambient air quality” in which restrictions on air pollution have increased in recent decades, Dr. Grande and coinvestigators noted. “Interestingly, the higher limit reported herein is not only below the current European limit for fine particulate matter but also below the US standard. In other words, we were able to establish harmful effects at levels below current standards,” they wrote.
In analyses of effect modification, the elevation of risk related to particulate matter ≤2.5 mcm exposure and nitrogen oxide exposure was significantly greater among older adults who had heart failure (HRs, 1.93 and 1.43, respectively). Risk was marginally greater among those with ischemic heart disease (HRs, 1.67 and 1.36, respectively).
Analyses of potential mediators showed that preceding stroke accounted for the largest share of all dementia cases related to particulate matter ≤2.5 mcm exposure, at 49.4%.
The stronger association for exposure in the past 5 years is noteworthy for the big picture, they added. “From a policy point of view, this result is encouraging because it might imply that reducing air pollutant levels today could yield better outcomes already in the shorter term, reinforcing the need for appropriately set air quality standards,” they said.
Dr. Grande disclosed no relevant conflicts of interest. The study was funded by the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K); the Swedish Ministry of Health and Social Affairs; the participating County Councils and Municipalities; the Swedish Research Council; funding for doctoral education from the Karolinska Institutet; and the Swedish Research Council for Health, Working Life and Welfare.
SOURCE: Grande G et al. JAMA Neurol. 2020. doi:10.1001/jamaneurol.2019.4914.
Virtually all of the association between air pollution and dementia seemed to occur through the presence or the development of cardiovascular disease, which suggests a need to optimize treatment of concurrent cardiovascular disease and risk-factor control in older adults at higher risk for dementia and living in polluted urban areas, said lead author Giulia Grande, MD, a researcher at the Aging Research Center, Karolinska Institutet and Stockholm University, in Solna, Sweden.
In the longitudinal, population-based cohort study, investigators studied 2,927 randomly selected residents in a district of Stockholm who were aged 60 years or older (mean, 74.1 years), lived at home or in institutions, and were free of dementia at baseline (March 2001 through August 2004).
The investigators assessed the participants’ exposure to two major air pollutants – particulate matter ≤2.5 mcm and nitrogen oxide – yearly starting in 1990, from outdoor levels at their residential addresses. Both pollutants are generated by road traffic, among other sources.
Results reported in JAMA Neurology showed that, with a mean follow-up of 6.01 years, 12.4% of the older adults received a dementia diagnosis.
Dementia risk increased with the level of air pollutants at their residential address in the past, with strongest associations seen for exposure in the preceding 5 years: The hazard ratio (HR) for dementia was 1.54 for an interquartile range difference of 0.88 mcg/m3 in particulate matter ≤2.5 mcm and 1.14 for an interquartile range difference of 8.35 mcg/m3 in nitrogen oxide during that time period.
Of note, the study cohort lived in an area having “comparatively good ambient air quality” in which restrictions on air pollution have increased in recent decades, Dr. Grande and coinvestigators noted. “Interestingly, the higher limit reported herein is not only below the current European limit for fine particulate matter but also below the US standard. In other words, we were able to establish harmful effects at levels below current standards,” they wrote.
In analyses of effect modification, the elevation of risk related to particulate matter ≤2.5 mcm exposure and nitrogen oxide exposure was significantly greater among older adults who had heart failure (HRs, 1.93 and 1.43, respectively). Risk was marginally greater among those with ischemic heart disease (HRs, 1.67 and 1.36, respectively).
Analyses of potential mediators showed that preceding stroke accounted for the largest share of all dementia cases related to particulate matter ≤2.5 mcm exposure, at 49.4%.
The stronger association for exposure in the past 5 years is noteworthy for the big picture, they added. “From a policy point of view, this result is encouraging because it might imply that reducing air pollutant levels today could yield better outcomes already in the shorter term, reinforcing the need for appropriately set air quality standards,” they said.
Dr. Grande disclosed no relevant conflicts of interest. The study was funded by the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K); the Swedish Ministry of Health and Social Affairs; the participating County Councils and Municipalities; the Swedish Research Council; funding for doctoral education from the Karolinska Institutet; and the Swedish Research Council for Health, Working Life and Welfare.
SOURCE: Grande G et al. JAMA Neurol. 2020. doi:10.1001/jamaneurol.2019.4914.
Virtually all of the association between air pollution and dementia seemed to occur through the presence or the development of cardiovascular disease, which suggests a need to optimize treatment of concurrent cardiovascular disease and risk-factor control in older adults at higher risk for dementia and living in polluted urban areas, said lead author Giulia Grande, MD, a researcher at the Aging Research Center, Karolinska Institutet and Stockholm University, in Solna, Sweden.
In the longitudinal, population-based cohort study, investigators studied 2,927 randomly selected residents in a district of Stockholm who were aged 60 years or older (mean, 74.1 years), lived at home or in institutions, and were free of dementia at baseline (March 2001 through August 2004).
The investigators assessed the participants’ exposure to two major air pollutants – particulate matter ≤2.5 mcm and nitrogen oxide – yearly starting in 1990, from outdoor levels at their residential addresses. Both pollutants are generated by road traffic, among other sources.
Results reported in JAMA Neurology showed that, with a mean follow-up of 6.01 years, 12.4% of the older adults received a dementia diagnosis.
Dementia risk increased with the level of air pollutants at their residential address in the past, with strongest associations seen for exposure in the preceding 5 years: The hazard ratio (HR) for dementia was 1.54 for an interquartile range difference of 0.88 mcg/m3 in particulate matter ≤2.5 mcm and 1.14 for an interquartile range difference of 8.35 mcg/m3 in nitrogen oxide during that time period.
Of note, the study cohort lived in an area having “comparatively good ambient air quality” in which restrictions on air pollution have increased in recent decades, Dr. Grande and coinvestigators noted. “Interestingly, the higher limit reported herein is not only below the current European limit for fine particulate matter but also below the US standard. In other words, we were able to establish harmful effects at levels below current standards,” they wrote.
In analyses of effect modification, the elevation of risk related to particulate matter ≤2.5 mcm exposure and nitrogen oxide exposure was significantly greater among older adults who had heart failure (HRs, 1.93 and 1.43, respectively). Risk was marginally greater among those with ischemic heart disease (HRs, 1.67 and 1.36, respectively).
Analyses of potential mediators showed that preceding stroke accounted for the largest share of all dementia cases related to particulate matter ≤2.5 mcm exposure, at 49.4%.
The stronger association for exposure in the past 5 years is noteworthy for the big picture, they added. “From a policy point of view, this result is encouraging because it might imply that reducing air pollutant levels today could yield better outcomes already in the shorter term, reinforcing the need for appropriately set air quality standards,” they said.
Dr. Grande disclosed no relevant conflicts of interest. The study was funded by the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K); the Swedish Ministry of Health and Social Affairs; the participating County Councils and Municipalities; the Swedish Research Council; funding for doctoral education from the Karolinska Institutet; and the Swedish Research Council for Health, Working Life and Welfare.
SOURCE: Grande G et al. JAMA Neurol. 2020. doi:10.1001/jamaneurol.2019.4914.
FROM JAMA NEUROLOGY
Renal denervation shown safe and effective in pivotal trial
Catheter-based renal denervation took a step closer to attaining legitimacy as a nonpharmacologic treatment for hypertension with presentation of the primary results of the SPYRAL HTN-OFF MED pivotal trial at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. The meeting was conducted online after its cancellation because of the COVID-19 pandemic.
“We saw clinically meaningful blood pressure reductions at 3 months,” reported Michael Boehm, MD, chief of cardiology at Saarland University Hospital in Homburg, Germany.
That’s encouraging news, as renal denervation (RDN) was nearly abandoned as a potential treatment for hypertension in the wake of the unexpectedly negative results of the SYMPLICITY HTN-3 trial (N Engl J Med. 2014;370:1393-401). However, post hoc analysis of the trial revealed significant shortcomings in design and execution, and a more rigorous development program for the percutaneous device-based therapy is well underway.
The SPYRAL HTN-OFF MED pivotal trial was designed under Food and Drug Administration guidance to show whether RDN reduces blood pressure in patients with untreated hypertension. The prospective study included 331 off-medication patients in nine countries who were randomized to RDN or a sham procedure, then followed in double-blind fashion for 3 months.
The primary outcome was change in 24-hour ambulatory systolic blood pressure from baseline to 3 months. From a mean baseline 24-hour ambulatory blood pressure of 151.4/98 mm Hg, patients in the RDN group averaged a 4.7 mm Hg decrease in 24-hour SBP, which was 4 mm Hg more than in sham-treated controls. Statistically, this translated to a greater than 99.9% probability that RDN was superior to sham therapy. The RDN group also experienced a mean 3.7–mm Hg reduction in 24-hour DBP, compared with a 0.8–mm Hg decrease in controls.
Office SBP – the secondary endpoint – decreased by a mean of 9.2 mm Hg with RDN, compared with 2.5 mm Hg in controls.
These results probably understate the true antihypertensive effect of RDN for two reasons, Dr. Boehm noted. For one, previous studies have shown that the magnitude of blood pressure lowering continues to increase for up to 1-2 years following the procedure, whereas the off-medication assessment in SPYRAL HTN-OFF MED ended at 3 months for ethical and safety reasons. Also, 17% of patients in the control arm were withdrawn from the study and placed on antihypertensive medication because their office SBP reached 180 mm Hg or more, as compared to 9.6% of the RDN group.
A key finding was that RDN lowered blood pressure around the clock, including nighttime and early morning, the hours of greatest cardiovascular risk and a time when some antihypertensive medications are less effective at blood pressure control, the cardiologist observed.
The RDN safety picture was reassuring, with no strokes, myocardial infarctions, major bleeding, or acute deterioration in kidney function.
A surprising finding was that, even though participants underwent blood and urine testing for the presence of antihypertensive drugs at baseline to ensure they were off medication, and were told they would be retested at 3 months, 5%-9% nonetheless tested positive at the second test.
That elicited a comment from session chair Richard A. Chazal, MD, of Fort Myers, Fla.: “I must say, as a clinician who sometimes has trouble getting his patients to take antihypertensives, it’s fascinating that some of the people that you asked not to take the medications were taking them.”
While the primary outcome in SPYRAL HTN-OFF MED was the 3-month reduction in blood pressure while off of antihypertensive medication, the ongoing second phase of the trial may have greater clinical relevance. At 3 months, participants are being placed on antihypertensive medication and uptitrated to target, with unblinding at 6 months. The purpose is to see how many RDN recipients don’t need antihypertensive drugs, as well as whether those that do require less medication than the patients who didn’t undergo RDN.
Dr. Boehm characterized RDN as a work in progress. Two major limitations that are the focus of intense research are the lack of a predictor as to which patients are most likely to respond to what is after all an invasive procedure, and the current inability intraprocedurally to tell if sufficient RDN has been achieved.
“Frankly speaking, there is no technology during the procedure to see how efficacious the procedure was,” he explained.
Discussant Dhanunaja Lakkireddy, MD, deemed the mean 4.7–mm Hg reduction in 24-hour SBP “reasonably impressive – that’s actually a pretty good number for an antihypertensive clinical trial.” He was also favorably impressed by RDN’s safety in a 44-site study.
“The drops in blood pressure are not enough to really make a case for renal denervation to be a standalone therapy. But adding it as an adjunct to standard medications may be a very reasonable strategy to adopt. This is a fantastic signal for something that can be brought along as a long-term add-on to antihypertensive medications,” commented Dr. Lakkireddy, chair of the ACC Electrophysiology Council and medical director of the Kansas City Heart Rhythm Institute.
Simultaneous with Dr. Boehm’s presentation, the SPYRAL HTN-OFF MED Pivotal Trial details were published online (Lancet 2020 Mar 29. doi: 10.1016/S0140-6736(20)30554-7).
The study was sponsored by Medtronic. Dr. Boehm reported serving as a consultant to that company and Abbott, Amgen, Astra, Boehringer-Ingelheim, Cytokinetics, Novartis, ReCor, Servier, and Vifor.
SOURCE: Boehm M. ACC 2020, Abstract 406-15.
Catheter-based renal denervation took a step closer to attaining legitimacy as a nonpharmacologic treatment for hypertension with presentation of the primary results of the SPYRAL HTN-OFF MED pivotal trial at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. The meeting was conducted online after its cancellation because of the COVID-19 pandemic.
“We saw clinically meaningful blood pressure reductions at 3 months,” reported Michael Boehm, MD, chief of cardiology at Saarland University Hospital in Homburg, Germany.
That’s encouraging news, as renal denervation (RDN) was nearly abandoned as a potential treatment for hypertension in the wake of the unexpectedly negative results of the SYMPLICITY HTN-3 trial (N Engl J Med. 2014;370:1393-401). However, post hoc analysis of the trial revealed significant shortcomings in design and execution, and a more rigorous development program for the percutaneous device-based therapy is well underway.
The SPYRAL HTN-OFF MED pivotal trial was designed under Food and Drug Administration guidance to show whether RDN reduces blood pressure in patients with untreated hypertension. The prospective study included 331 off-medication patients in nine countries who were randomized to RDN or a sham procedure, then followed in double-blind fashion for 3 months.
The primary outcome was change in 24-hour ambulatory systolic blood pressure from baseline to 3 months. From a mean baseline 24-hour ambulatory blood pressure of 151.4/98 mm Hg, patients in the RDN group averaged a 4.7 mm Hg decrease in 24-hour SBP, which was 4 mm Hg more than in sham-treated controls. Statistically, this translated to a greater than 99.9% probability that RDN was superior to sham therapy. The RDN group also experienced a mean 3.7–mm Hg reduction in 24-hour DBP, compared with a 0.8–mm Hg decrease in controls.
Office SBP – the secondary endpoint – decreased by a mean of 9.2 mm Hg with RDN, compared with 2.5 mm Hg in controls.
These results probably understate the true antihypertensive effect of RDN for two reasons, Dr. Boehm noted. For one, previous studies have shown that the magnitude of blood pressure lowering continues to increase for up to 1-2 years following the procedure, whereas the off-medication assessment in SPYRAL HTN-OFF MED ended at 3 months for ethical and safety reasons. Also, 17% of patients in the control arm were withdrawn from the study and placed on antihypertensive medication because their office SBP reached 180 mm Hg or more, as compared to 9.6% of the RDN group.
A key finding was that RDN lowered blood pressure around the clock, including nighttime and early morning, the hours of greatest cardiovascular risk and a time when some antihypertensive medications are less effective at blood pressure control, the cardiologist observed.
The RDN safety picture was reassuring, with no strokes, myocardial infarctions, major bleeding, or acute deterioration in kidney function.
A surprising finding was that, even though participants underwent blood and urine testing for the presence of antihypertensive drugs at baseline to ensure they were off medication, and were told they would be retested at 3 months, 5%-9% nonetheless tested positive at the second test.
That elicited a comment from session chair Richard A. Chazal, MD, of Fort Myers, Fla.: “I must say, as a clinician who sometimes has trouble getting his patients to take antihypertensives, it’s fascinating that some of the people that you asked not to take the medications were taking them.”
While the primary outcome in SPYRAL HTN-OFF MED was the 3-month reduction in blood pressure while off of antihypertensive medication, the ongoing second phase of the trial may have greater clinical relevance. At 3 months, participants are being placed on antihypertensive medication and uptitrated to target, with unblinding at 6 months. The purpose is to see how many RDN recipients don’t need antihypertensive drugs, as well as whether those that do require less medication than the patients who didn’t undergo RDN.
Dr. Boehm characterized RDN as a work in progress. Two major limitations that are the focus of intense research are the lack of a predictor as to which patients are most likely to respond to what is after all an invasive procedure, and the current inability intraprocedurally to tell if sufficient RDN has been achieved.
“Frankly speaking, there is no technology during the procedure to see how efficacious the procedure was,” he explained.
Discussant Dhanunaja Lakkireddy, MD, deemed the mean 4.7–mm Hg reduction in 24-hour SBP “reasonably impressive – that’s actually a pretty good number for an antihypertensive clinical trial.” He was also favorably impressed by RDN’s safety in a 44-site study.
“The drops in blood pressure are not enough to really make a case for renal denervation to be a standalone therapy. But adding it as an adjunct to standard medications may be a very reasonable strategy to adopt. This is a fantastic signal for something that can be brought along as a long-term add-on to antihypertensive medications,” commented Dr. Lakkireddy, chair of the ACC Electrophysiology Council and medical director of the Kansas City Heart Rhythm Institute.
Simultaneous with Dr. Boehm’s presentation, the SPYRAL HTN-OFF MED Pivotal Trial details were published online (Lancet 2020 Mar 29. doi: 10.1016/S0140-6736(20)30554-7).
The study was sponsored by Medtronic. Dr. Boehm reported serving as a consultant to that company and Abbott, Amgen, Astra, Boehringer-Ingelheim, Cytokinetics, Novartis, ReCor, Servier, and Vifor.
SOURCE: Boehm M. ACC 2020, Abstract 406-15.
Catheter-based renal denervation took a step closer to attaining legitimacy as a nonpharmacologic treatment for hypertension with presentation of the primary results of the SPYRAL HTN-OFF MED pivotal trial at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. The meeting was conducted online after its cancellation because of the COVID-19 pandemic.
“We saw clinically meaningful blood pressure reductions at 3 months,” reported Michael Boehm, MD, chief of cardiology at Saarland University Hospital in Homburg, Germany.
That’s encouraging news, as renal denervation (RDN) was nearly abandoned as a potential treatment for hypertension in the wake of the unexpectedly negative results of the SYMPLICITY HTN-3 trial (N Engl J Med. 2014;370:1393-401). However, post hoc analysis of the trial revealed significant shortcomings in design and execution, and a more rigorous development program for the percutaneous device-based therapy is well underway.
The SPYRAL HTN-OFF MED pivotal trial was designed under Food and Drug Administration guidance to show whether RDN reduces blood pressure in patients with untreated hypertension. The prospective study included 331 off-medication patients in nine countries who were randomized to RDN or a sham procedure, then followed in double-blind fashion for 3 months.
The primary outcome was change in 24-hour ambulatory systolic blood pressure from baseline to 3 months. From a mean baseline 24-hour ambulatory blood pressure of 151.4/98 mm Hg, patients in the RDN group averaged a 4.7 mm Hg decrease in 24-hour SBP, which was 4 mm Hg more than in sham-treated controls. Statistically, this translated to a greater than 99.9% probability that RDN was superior to sham therapy. The RDN group also experienced a mean 3.7–mm Hg reduction in 24-hour DBP, compared with a 0.8–mm Hg decrease in controls.
Office SBP – the secondary endpoint – decreased by a mean of 9.2 mm Hg with RDN, compared with 2.5 mm Hg in controls.
These results probably understate the true antihypertensive effect of RDN for two reasons, Dr. Boehm noted. For one, previous studies have shown that the magnitude of blood pressure lowering continues to increase for up to 1-2 years following the procedure, whereas the off-medication assessment in SPYRAL HTN-OFF MED ended at 3 months for ethical and safety reasons. Also, 17% of patients in the control arm were withdrawn from the study and placed on antihypertensive medication because their office SBP reached 180 mm Hg or more, as compared to 9.6% of the RDN group.
A key finding was that RDN lowered blood pressure around the clock, including nighttime and early morning, the hours of greatest cardiovascular risk and a time when some antihypertensive medications are less effective at blood pressure control, the cardiologist observed.
The RDN safety picture was reassuring, with no strokes, myocardial infarctions, major bleeding, or acute deterioration in kidney function.
A surprising finding was that, even though participants underwent blood and urine testing for the presence of antihypertensive drugs at baseline to ensure they were off medication, and were told they would be retested at 3 months, 5%-9% nonetheless tested positive at the second test.
That elicited a comment from session chair Richard A. Chazal, MD, of Fort Myers, Fla.: “I must say, as a clinician who sometimes has trouble getting his patients to take antihypertensives, it’s fascinating that some of the people that you asked not to take the medications were taking them.”
While the primary outcome in SPYRAL HTN-OFF MED was the 3-month reduction in blood pressure while off of antihypertensive medication, the ongoing second phase of the trial may have greater clinical relevance. At 3 months, participants are being placed on antihypertensive medication and uptitrated to target, with unblinding at 6 months. The purpose is to see how many RDN recipients don’t need antihypertensive drugs, as well as whether those that do require less medication than the patients who didn’t undergo RDN.
Dr. Boehm characterized RDN as a work in progress. Two major limitations that are the focus of intense research are the lack of a predictor as to which patients are most likely to respond to what is after all an invasive procedure, and the current inability intraprocedurally to tell if sufficient RDN has been achieved.
“Frankly speaking, there is no technology during the procedure to see how efficacious the procedure was,” he explained.
Discussant Dhanunaja Lakkireddy, MD, deemed the mean 4.7–mm Hg reduction in 24-hour SBP “reasonably impressive – that’s actually a pretty good number for an antihypertensive clinical trial.” He was also favorably impressed by RDN’s safety in a 44-site study.
“The drops in blood pressure are not enough to really make a case for renal denervation to be a standalone therapy. But adding it as an adjunct to standard medications may be a very reasonable strategy to adopt. This is a fantastic signal for something that can be brought along as a long-term add-on to antihypertensive medications,” commented Dr. Lakkireddy, chair of the ACC Electrophysiology Council and medical director of the Kansas City Heart Rhythm Institute.
Simultaneous with Dr. Boehm’s presentation, the SPYRAL HTN-OFF MED Pivotal Trial details were published online (Lancet 2020 Mar 29. doi: 10.1016/S0140-6736(20)30554-7).
The study was sponsored by Medtronic. Dr. Boehm reported serving as a consultant to that company and Abbott, Amgen, Astra, Boehringer-Ingelheim, Cytokinetics, Novartis, ReCor, Servier, and Vifor.
SOURCE: Boehm M. ACC 2020, Abstract 406-15.
REPORTING FROM ACC 20
Intracranial artery stenting shows promising 1-year results
LOS ANGELES –
One-year after 129 patients received an intracranial stent that’s already on the U.S. market for treating severe atherosclerotic disease following an ischemic stroke, their incidence of death or repeat stroke was 9%, low enough to suggest benefit compared with historic control patients who were medically managed and had a 12% 1-year rate of death or stroke. This signal of incremental benefit from intracranial stenting may help spark renewed interest in an intervention that was largely forsaken in recent years because of safety concerns.
Assessing restenosis frequency
“Stenting seemed to confer some protection against severe or fatal strokes” in a study that provided “the largest 1-year follow-up of stenting” for intracranial atherosclerotic disease, the trigger for roughly 10% of all U.S. stroke cases, Michael J. Alexander, MD, said at the International Stroke Conference, sponsored by the American Heart Association.
What 1-year follow-up highlighted was the restenosis frequency, based on imaging follow-up for 107 of these 129 patients who had received a Wingspan nitinol, self-expanding stent. Seven patients developed symptomatic restenosis in the region of stent placement, and another 11 patients had asymptomatic restenosis that occluded at least 70% of the stented artery, a total 1-year restenosis rate of 18/107 (17%), reported Dr. Alexander, professor of neurosurgery and director of the Neurovascular Center at Cedars-Sinai Medical Center in Los Angeles. The mean time to detection of restenosis was 5 months, with a range of 1-11 months.
Intracranial stenting falls out of favor
The tested Wingspan stent first received Food and Drug Administration approval for intracranial artery placement in 2005, and then in August 2012 the agency tightened the labeled indication to a much smaller, more specifically defined group of patients: those 22-80 years old, with 70%-99% stenosis in a cerebral artery, with a history of at least two strokes, with stent placement timed more than 7 days following the most recent stroke, and refractory to medical therapy. This 2012 label change came in response to a concerning rate of periprocedural complications in patients who received intracrania artery stents as part of a study reported in 2011 that included many patients with clinical characteristics that fell outside the limits the agency later set in 2012. Results from the SAMMPRIS (Stenting vs. Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis) trial showed that among 451 randomized patients the 224 assigned to stenting had a 15% 30-day rate of death or stroke, compared with a 6% rate among control patients who did not receive a stent, a statistically significant difference that led to early stopping of the trial (New Engl J Med. 2011 Sep 15;365[11]:993-1003). At least half of the patients who received a stent in SAMMPRIS were 7 or fewer days out from their index event, a majority had either a single prior stroke or transient ischemic attack as their index event, and many had not been established as refractory to medical management.
The SAMMPRIS results and the subsequent relabeling of the Wingspan stent by the FDA had two consequences. First came a steep drop in the use of intracranial stenting. After SAMMPRIS, vascular neurologists “abandoned the stent; no one does intracranial stenting” today, commented Louise D. McCullough, MD, professor and chair of neurology at the University of Texas Health Science Center at Houston. The second consequence was an FDA mandate to run a new randomized study to reassess the periprocedural complications when clinicians placed the Wingspan intracranial stent in patients who fully matched the revised 2012 labeling.
That mandated study was the WEAVE (Post Market Surveillance Study of the Wingspan Stent System) trial, which enrolled 152 patients at 24 U.S. sites in a single-arm study, and found a 2.6% rate of death or stroke during the 30 days following intervention that beat the 4% benchmark rate prespecified in the trial’s design (Stroke. 2019 Apr;50[4]:889-94). The WEAVE findings provided even more evidence of the need for the tight labeling the device received in 2012. A safety communication from the FDA in April 2019 noted that an additional 46 patients received an intracranial artery stent during WEAVE despite falling outside the 2012 labeled indications, and this off-label group had a 24% incidence of periprocedural complications, compared with the 2.6% rate in the on-label group. The FDA’s statement reaffirmed the labeling restrictions and highlighted additional cautions and recommendations for using the device.
The WOVEN study
The 1-year follow-up of the WEAVE patients, an extension called the WOVEN (Wingspan One Year Vascular Imaging Events and Neurologic Outcomes) study, was investigator initiated with no commercial funding and included 129 of the original on-label patients (85%) at 15 of the original 24 participating centers.
In addition to the data collected in WOVEN on restenosis rates, follow-up tallied seven patients with a stroke in the vascular territory of the stent during the period that began 30 days after the procedure (when the WEAVE follow-up finished) and continued through 12 months, with no neurologic deaths. When combined with the 4 periprocedural events that occurred during WEAVE, the final WOVEN tally was 11 total events in 129 patients followed for 1 year (9%). Because WEAVE and WOVEN included no control patients, Dr. Alexander compared this 1-year incidence rate with the 12% rate among medically managed control patients in SAMMPRIS.
According to Dr. Alexander, the next step in the path to rehabilitating a clinical role for intracranial stenting is a new randomized study that compares stenting used exclusively to the 2012 labeling with medical management in high-risk patients, those with hemodynamic compromise.
Encouraging data, but is it compelling?
“There may be a benefit” from intracranial stenting, but “we need a larger trial to convince people” said Dr. McCullough. The WEAVE and new WOVEN findings provide a “signal that stenting may be better than medical therapy, but this was only in just over 100 patients. We’ll need a larger study,” she said in an interview. The findings also reinforced that restenosis remains a challenge for intracranial artery stenting.
“Intracranial atherosclerosis is very difficult to treat, and we need new strategies for these patients.” The WEAVE and WOVEN results “suggest that while the restenosis rate may be high, it may also be manageable.” Delaying stent placement to no sooner than 8 days after a stroke may be a key step for improving safety, but new approaches are also need to minimize the restenosis risk, Dr. McCullough noted.
WEAVE was sponsored by Stryker Neurovascular, the company that markets the Wingspan intracranial artery stent. WOVEN received no commercial funding. Dr. Alexander has been a consultant to Stryker Neurovascular. Dr. McCullough had no disclosures.
SOURCE: Alexander MJ et al. International Stroke Conference, Abstract LB4.
LOS ANGELES –
One-year after 129 patients received an intracranial stent that’s already on the U.S. market for treating severe atherosclerotic disease following an ischemic stroke, their incidence of death or repeat stroke was 9%, low enough to suggest benefit compared with historic control patients who were medically managed and had a 12% 1-year rate of death or stroke. This signal of incremental benefit from intracranial stenting may help spark renewed interest in an intervention that was largely forsaken in recent years because of safety concerns.
Assessing restenosis frequency
“Stenting seemed to confer some protection against severe or fatal strokes” in a study that provided “the largest 1-year follow-up of stenting” for intracranial atherosclerotic disease, the trigger for roughly 10% of all U.S. stroke cases, Michael J. Alexander, MD, said at the International Stroke Conference, sponsored by the American Heart Association.
What 1-year follow-up highlighted was the restenosis frequency, based on imaging follow-up for 107 of these 129 patients who had received a Wingspan nitinol, self-expanding stent. Seven patients developed symptomatic restenosis in the region of stent placement, and another 11 patients had asymptomatic restenosis that occluded at least 70% of the stented artery, a total 1-year restenosis rate of 18/107 (17%), reported Dr. Alexander, professor of neurosurgery and director of the Neurovascular Center at Cedars-Sinai Medical Center in Los Angeles. The mean time to detection of restenosis was 5 months, with a range of 1-11 months.
Intracranial stenting falls out of favor
The tested Wingspan stent first received Food and Drug Administration approval for intracranial artery placement in 2005, and then in August 2012 the agency tightened the labeled indication to a much smaller, more specifically defined group of patients: those 22-80 years old, with 70%-99% stenosis in a cerebral artery, with a history of at least two strokes, with stent placement timed more than 7 days following the most recent stroke, and refractory to medical therapy. This 2012 label change came in response to a concerning rate of periprocedural complications in patients who received intracrania artery stents as part of a study reported in 2011 that included many patients with clinical characteristics that fell outside the limits the agency later set in 2012. Results from the SAMMPRIS (Stenting vs. Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis) trial showed that among 451 randomized patients the 224 assigned to stenting had a 15% 30-day rate of death or stroke, compared with a 6% rate among control patients who did not receive a stent, a statistically significant difference that led to early stopping of the trial (New Engl J Med. 2011 Sep 15;365[11]:993-1003). At least half of the patients who received a stent in SAMMPRIS were 7 or fewer days out from their index event, a majority had either a single prior stroke or transient ischemic attack as their index event, and many had not been established as refractory to medical management.
The SAMMPRIS results and the subsequent relabeling of the Wingspan stent by the FDA had two consequences. First came a steep drop in the use of intracranial stenting. After SAMMPRIS, vascular neurologists “abandoned the stent; no one does intracranial stenting” today, commented Louise D. McCullough, MD, professor and chair of neurology at the University of Texas Health Science Center at Houston. The second consequence was an FDA mandate to run a new randomized study to reassess the periprocedural complications when clinicians placed the Wingspan intracranial stent in patients who fully matched the revised 2012 labeling.
That mandated study was the WEAVE (Post Market Surveillance Study of the Wingspan Stent System) trial, which enrolled 152 patients at 24 U.S. sites in a single-arm study, and found a 2.6% rate of death or stroke during the 30 days following intervention that beat the 4% benchmark rate prespecified in the trial’s design (Stroke. 2019 Apr;50[4]:889-94). The WEAVE findings provided even more evidence of the need for the tight labeling the device received in 2012. A safety communication from the FDA in April 2019 noted that an additional 46 patients received an intracranial artery stent during WEAVE despite falling outside the 2012 labeled indications, and this off-label group had a 24% incidence of periprocedural complications, compared with the 2.6% rate in the on-label group. The FDA’s statement reaffirmed the labeling restrictions and highlighted additional cautions and recommendations for using the device.
The WOVEN study
The 1-year follow-up of the WEAVE patients, an extension called the WOVEN (Wingspan One Year Vascular Imaging Events and Neurologic Outcomes) study, was investigator initiated with no commercial funding and included 129 of the original on-label patients (85%) at 15 of the original 24 participating centers.
In addition to the data collected in WOVEN on restenosis rates, follow-up tallied seven patients with a stroke in the vascular territory of the stent during the period that began 30 days after the procedure (when the WEAVE follow-up finished) and continued through 12 months, with no neurologic deaths. When combined with the 4 periprocedural events that occurred during WEAVE, the final WOVEN tally was 11 total events in 129 patients followed for 1 year (9%). Because WEAVE and WOVEN included no control patients, Dr. Alexander compared this 1-year incidence rate with the 12% rate among medically managed control patients in SAMMPRIS.
According to Dr. Alexander, the next step in the path to rehabilitating a clinical role for intracranial stenting is a new randomized study that compares stenting used exclusively to the 2012 labeling with medical management in high-risk patients, those with hemodynamic compromise.
Encouraging data, but is it compelling?
“There may be a benefit” from intracranial stenting, but “we need a larger trial to convince people” said Dr. McCullough. The WEAVE and new WOVEN findings provide a “signal that stenting may be better than medical therapy, but this was only in just over 100 patients. We’ll need a larger study,” she said in an interview. The findings also reinforced that restenosis remains a challenge for intracranial artery stenting.
“Intracranial atherosclerosis is very difficult to treat, and we need new strategies for these patients.” The WEAVE and WOVEN results “suggest that while the restenosis rate may be high, it may also be manageable.” Delaying stent placement to no sooner than 8 days after a stroke may be a key step for improving safety, but new approaches are also need to minimize the restenosis risk, Dr. McCullough noted.
WEAVE was sponsored by Stryker Neurovascular, the company that markets the Wingspan intracranial artery stent. WOVEN received no commercial funding. Dr. Alexander has been a consultant to Stryker Neurovascular. Dr. McCullough had no disclosures.
SOURCE: Alexander MJ et al. International Stroke Conference, Abstract LB4.
LOS ANGELES –
One-year after 129 patients received an intracranial stent that’s already on the U.S. market for treating severe atherosclerotic disease following an ischemic stroke, their incidence of death or repeat stroke was 9%, low enough to suggest benefit compared with historic control patients who were medically managed and had a 12% 1-year rate of death or stroke. This signal of incremental benefit from intracranial stenting may help spark renewed interest in an intervention that was largely forsaken in recent years because of safety concerns.
Assessing restenosis frequency
“Stenting seemed to confer some protection against severe or fatal strokes” in a study that provided “the largest 1-year follow-up of stenting” for intracranial atherosclerotic disease, the trigger for roughly 10% of all U.S. stroke cases, Michael J. Alexander, MD, said at the International Stroke Conference, sponsored by the American Heart Association.
What 1-year follow-up highlighted was the restenosis frequency, based on imaging follow-up for 107 of these 129 patients who had received a Wingspan nitinol, self-expanding stent. Seven patients developed symptomatic restenosis in the region of stent placement, and another 11 patients had asymptomatic restenosis that occluded at least 70% of the stented artery, a total 1-year restenosis rate of 18/107 (17%), reported Dr. Alexander, professor of neurosurgery and director of the Neurovascular Center at Cedars-Sinai Medical Center in Los Angeles. The mean time to detection of restenosis was 5 months, with a range of 1-11 months.
Intracranial stenting falls out of favor
The tested Wingspan stent first received Food and Drug Administration approval for intracranial artery placement in 2005, and then in August 2012 the agency tightened the labeled indication to a much smaller, more specifically defined group of patients: those 22-80 years old, with 70%-99% stenosis in a cerebral artery, with a history of at least two strokes, with stent placement timed more than 7 days following the most recent stroke, and refractory to medical therapy. This 2012 label change came in response to a concerning rate of periprocedural complications in patients who received intracrania artery stents as part of a study reported in 2011 that included many patients with clinical characteristics that fell outside the limits the agency later set in 2012. Results from the SAMMPRIS (Stenting vs. Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis) trial showed that among 451 randomized patients the 224 assigned to stenting had a 15% 30-day rate of death or stroke, compared with a 6% rate among control patients who did not receive a stent, a statistically significant difference that led to early stopping of the trial (New Engl J Med. 2011 Sep 15;365[11]:993-1003). At least half of the patients who received a stent in SAMMPRIS were 7 or fewer days out from their index event, a majority had either a single prior stroke or transient ischemic attack as their index event, and many had not been established as refractory to medical management.
The SAMMPRIS results and the subsequent relabeling of the Wingspan stent by the FDA had two consequences. First came a steep drop in the use of intracranial stenting. After SAMMPRIS, vascular neurologists “abandoned the stent; no one does intracranial stenting” today, commented Louise D. McCullough, MD, professor and chair of neurology at the University of Texas Health Science Center at Houston. The second consequence was an FDA mandate to run a new randomized study to reassess the periprocedural complications when clinicians placed the Wingspan intracranial stent in patients who fully matched the revised 2012 labeling.
That mandated study was the WEAVE (Post Market Surveillance Study of the Wingspan Stent System) trial, which enrolled 152 patients at 24 U.S. sites in a single-arm study, and found a 2.6% rate of death or stroke during the 30 days following intervention that beat the 4% benchmark rate prespecified in the trial’s design (Stroke. 2019 Apr;50[4]:889-94). The WEAVE findings provided even more evidence of the need for the tight labeling the device received in 2012. A safety communication from the FDA in April 2019 noted that an additional 46 patients received an intracranial artery stent during WEAVE despite falling outside the 2012 labeled indications, and this off-label group had a 24% incidence of periprocedural complications, compared with the 2.6% rate in the on-label group. The FDA’s statement reaffirmed the labeling restrictions and highlighted additional cautions and recommendations for using the device.
The WOVEN study
The 1-year follow-up of the WEAVE patients, an extension called the WOVEN (Wingspan One Year Vascular Imaging Events and Neurologic Outcomes) study, was investigator initiated with no commercial funding and included 129 of the original on-label patients (85%) at 15 of the original 24 participating centers.
In addition to the data collected in WOVEN on restenosis rates, follow-up tallied seven patients with a stroke in the vascular territory of the stent during the period that began 30 days after the procedure (when the WEAVE follow-up finished) and continued through 12 months, with no neurologic deaths. When combined with the 4 periprocedural events that occurred during WEAVE, the final WOVEN tally was 11 total events in 129 patients followed for 1 year (9%). Because WEAVE and WOVEN included no control patients, Dr. Alexander compared this 1-year incidence rate with the 12% rate among medically managed control patients in SAMMPRIS.
According to Dr. Alexander, the next step in the path to rehabilitating a clinical role for intracranial stenting is a new randomized study that compares stenting used exclusively to the 2012 labeling with medical management in high-risk patients, those with hemodynamic compromise.
Encouraging data, but is it compelling?
“There may be a benefit” from intracranial stenting, but “we need a larger trial to convince people” said Dr. McCullough. The WEAVE and new WOVEN findings provide a “signal that stenting may be better than medical therapy, but this was only in just over 100 patients. We’ll need a larger study,” she said in an interview. The findings also reinforced that restenosis remains a challenge for intracranial artery stenting.
“Intracranial atherosclerosis is very difficult to treat, and we need new strategies for these patients.” The WEAVE and WOVEN results “suggest that while the restenosis rate may be high, it may also be manageable.” Delaying stent placement to no sooner than 8 days after a stroke may be a key step for improving safety, but new approaches are also need to minimize the restenosis risk, Dr. McCullough noted.
WEAVE was sponsored by Stryker Neurovascular, the company that markets the Wingspan intracranial artery stent. WOVEN received no commercial funding. Dr. Alexander has been a consultant to Stryker Neurovascular. Dr. McCullough had no disclosures.
SOURCE: Alexander MJ et al. International Stroke Conference, Abstract LB4.
REPORTING FROM ISC 2020
ICH survival lags in the community setting
LOS ANGELES – Although recent findings from circumscribed patient populations enrolled in intervention studies have shown improved survival rates in patients with a recent intracerebral hemorrhagic stroke, data from a large, observational study in the Netherlands suggested a much darker real-world picture, with a 6-month mortality of 64% identified in a total cohort of nearly 15,000 people followed prospectively starting in 1990.
In striking contrast to the survival pattern over time of patients in the same Dutch study who had a first acute ischemic stroke, which showed a statistically significant and meaningful cut in mortality for ischemic stroke patients during the 25-year period examined, survival rates for patients during the first months following a first intracerebral hemorrhage (ICH) stayed flat during 1991-2015, Reem Waziry, MD, said at the International Stroke Conference sponsored by the American Heart Association.
“The promising treatment advances [applied to patients] in the recent ICH trials may not be reflected in community-based treatment,” suggested Dr. Waziry, a research and teaching fellow in clinical epidemiology at the Harvard School of Public Health in Boston.
The data she reported came from the Rotterdam Study, which followed unselected, older people in the Rotterdam community with no stroke history, and during 25 years of monitoring identified 162 incident ICH strokes and 988 acute ischemic strokes. Concurrently with Dr. Waziry’s talk at the conference, the data she reported were published in Stroke. The data she reported also showed that, during the 25 years studied, mortality at 3 years following a first ICH stroke rose to 73% on average.
During her talk, Dr. Waziry also presented an unpublished comparison of the 64% 6-month mortality in the Rotterdam Study with the 3- to 6-month mortality reported in the control arms of four recent, randomized intervention trials, including the MISTIE III trial. Among the four randomized trials Dr. Waziry selected to make this post-hoc comparison, the study with the highest mortality among control patients was MISTIE III, which showed about 25% mortality after 6 months. In contrast, the 19% 6-month mortality among ischemic stroke patients in the Rotterdam Study was roughly similar to the mortality seem in the control arms of some recent studies of interventions for patients with acute ischemic stroke.
The Rotterdam Study receives no commercial funding. Dr. Waziry had no disclosures.
SOURCE: Waziry R et al. ISC 2020, Abstract LB14.
LOS ANGELES – Although recent findings from circumscribed patient populations enrolled in intervention studies have shown improved survival rates in patients with a recent intracerebral hemorrhagic stroke, data from a large, observational study in the Netherlands suggested a much darker real-world picture, with a 6-month mortality of 64% identified in a total cohort of nearly 15,000 people followed prospectively starting in 1990.
In striking contrast to the survival pattern over time of patients in the same Dutch study who had a first acute ischemic stroke, which showed a statistically significant and meaningful cut in mortality for ischemic stroke patients during the 25-year period examined, survival rates for patients during the first months following a first intracerebral hemorrhage (ICH) stayed flat during 1991-2015, Reem Waziry, MD, said at the International Stroke Conference sponsored by the American Heart Association.
“The promising treatment advances [applied to patients] in the recent ICH trials may not be reflected in community-based treatment,” suggested Dr. Waziry, a research and teaching fellow in clinical epidemiology at the Harvard School of Public Health in Boston.
The data she reported came from the Rotterdam Study, which followed unselected, older people in the Rotterdam community with no stroke history, and during 25 years of monitoring identified 162 incident ICH strokes and 988 acute ischemic strokes. Concurrently with Dr. Waziry’s talk at the conference, the data she reported were published in Stroke. The data she reported also showed that, during the 25 years studied, mortality at 3 years following a first ICH stroke rose to 73% on average.
During her talk, Dr. Waziry also presented an unpublished comparison of the 64% 6-month mortality in the Rotterdam Study with the 3- to 6-month mortality reported in the control arms of four recent, randomized intervention trials, including the MISTIE III trial. Among the four randomized trials Dr. Waziry selected to make this post-hoc comparison, the study with the highest mortality among control patients was MISTIE III, which showed about 25% mortality after 6 months. In contrast, the 19% 6-month mortality among ischemic stroke patients in the Rotterdam Study was roughly similar to the mortality seem in the control arms of some recent studies of interventions for patients with acute ischemic stroke.
The Rotterdam Study receives no commercial funding. Dr. Waziry had no disclosures.
SOURCE: Waziry R et al. ISC 2020, Abstract LB14.
LOS ANGELES – Although recent findings from circumscribed patient populations enrolled in intervention studies have shown improved survival rates in patients with a recent intracerebral hemorrhagic stroke, data from a large, observational study in the Netherlands suggested a much darker real-world picture, with a 6-month mortality of 64% identified in a total cohort of nearly 15,000 people followed prospectively starting in 1990.
In striking contrast to the survival pattern over time of patients in the same Dutch study who had a first acute ischemic stroke, which showed a statistically significant and meaningful cut in mortality for ischemic stroke patients during the 25-year period examined, survival rates for patients during the first months following a first intracerebral hemorrhage (ICH) stayed flat during 1991-2015, Reem Waziry, MD, said at the International Stroke Conference sponsored by the American Heart Association.
“The promising treatment advances [applied to patients] in the recent ICH trials may not be reflected in community-based treatment,” suggested Dr. Waziry, a research and teaching fellow in clinical epidemiology at the Harvard School of Public Health in Boston.
The data she reported came from the Rotterdam Study, which followed unselected, older people in the Rotterdam community with no stroke history, and during 25 years of monitoring identified 162 incident ICH strokes and 988 acute ischemic strokes. Concurrently with Dr. Waziry’s talk at the conference, the data she reported were published in Stroke. The data she reported also showed that, during the 25 years studied, mortality at 3 years following a first ICH stroke rose to 73% on average.
During her talk, Dr. Waziry also presented an unpublished comparison of the 64% 6-month mortality in the Rotterdam Study with the 3- to 6-month mortality reported in the control arms of four recent, randomized intervention trials, including the MISTIE III trial. Among the four randomized trials Dr. Waziry selected to make this post-hoc comparison, the study with the highest mortality among control patients was MISTIE III, which showed about 25% mortality after 6 months. In contrast, the 19% 6-month mortality among ischemic stroke patients in the Rotterdam Study was roughly similar to the mortality seem in the control arms of some recent studies of interventions for patients with acute ischemic stroke.
The Rotterdam Study receives no commercial funding. Dr. Waziry had no disclosures.
SOURCE: Waziry R et al. ISC 2020, Abstract LB14.
REPORTING FROM ISC 2020
Get With the Guidelines – Stroke targets ICH
The Get With the Guidelines – Stroke program is finally turning its attention to hemorrhagic strokes after having spurred improved patient management performance from participating U.S. stroke centers since its start in 2003 with a focus on acute ischemic stroke.
The advisers who craft policy for Get With the Guidelines – Stroke (GWTG–S) are planning to launch a pilot program later in 2020 that will initiate data monitoring and quality improvement aimed at optimizing care for patients following an intracerebral hemorrhage (ICH) starting at 15 U.S. stroke centers, with announcement of these 15 participating centers expected later in 2020. The program will start by targeting nine specific, evidence-based, key aspects of the acute management of ICH patients, said Kevin N. Sheth, MD, professor of neurology and neurosurgery, and chief of neurocritical care and emergency neurology at Yale University in New Haven, Conn, and a volunteer expert who is part of the team developing the ICH initiative.
According to Dr. Sheth, the nine imperatives of acute ICH care that the program plans to monitor at participating centers are:
- Obtain a baseline severity score.
- Identify etiology as spontaneous or treatment related.
- Perform coagulopathy reversal or anticoagulant reversal.
- Administer venous thromboembolism prophylaxis.
- Apply dysphagia screening within 24 hours, and delay oral intake until patient passes dysphagia screen.
- Provide patient management in a multidisciplinary stroke or ICU unit.
- Prescribe appropriate blood pressure treatment at discharge.
- Perform assessment for rehabilitation.
- Avoid prescribing corticosteroids and other contraindicated drugs.
GWTG–S is adopting these metrics for assessing the acute care of ICH patients based largely on the recommendations of an expert 2018 panel organized by the American Heart Association and American Stroke. Association that proposed a set of performance measures for the care of ICH patients. This set of performance measures served as the primary basis for designing the new GWTG–S program, along with considerations of feasibility for collecting data on these measures, Dr. Sheth said in an interview. “We hope to make it easy” for centers to collect the data needed to participate.
The existing GWTG–S program is now 17-years old, and has spread to nearly 2,400 U.S. stroke centers as of early 2020, but the time has come to broaden its reach to patients with ICH and the programs that treat these patients, Dr. Sheth said. After years of nihilism about the prospects for patients following an ICH stroke, survival rates have increased, presenting “an opportunity to optimize care, for quality improvement,” he explained. “It’s a huge shift.” ICH patients “do better than we used to think.”
The Get With the Guidelines – Stroke program is finally turning its attention to hemorrhagic strokes after having spurred improved patient management performance from participating U.S. stroke centers since its start in 2003 with a focus on acute ischemic stroke.
The advisers who craft policy for Get With the Guidelines – Stroke (GWTG–S) are planning to launch a pilot program later in 2020 that will initiate data monitoring and quality improvement aimed at optimizing care for patients following an intracerebral hemorrhage (ICH) starting at 15 U.S. stroke centers, with announcement of these 15 participating centers expected later in 2020. The program will start by targeting nine specific, evidence-based, key aspects of the acute management of ICH patients, said Kevin N. Sheth, MD, professor of neurology and neurosurgery, and chief of neurocritical care and emergency neurology at Yale University in New Haven, Conn, and a volunteer expert who is part of the team developing the ICH initiative.
According to Dr. Sheth, the nine imperatives of acute ICH care that the program plans to monitor at participating centers are:
- Obtain a baseline severity score.
- Identify etiology as spontaneous or treatment related.
- Perform coagulopathy reversal or anticoagulant reversal.
- Administer venous thromboembolism prophylaxis.
- Apply dysphagia screening within 24 hours, and delay oral intake until patient passes dysphagia screen.
- Provide patient management in a multidisciplinary stroke or ICU unit.
- Prescribe appropriate blood pressure treatment at discharge.
- Perform assessment for rehabilitation.
- Avoid prescribing corticosteroids and other contraindicated drugs.
GWTG–S is adopting these metrics for assessing the acute care of ICH patients based largely on the recommendations of an expert 2018 panel organized by the American Heart Association and American Stroke. Association that proposed a set of performance measures for the care of ICH patients. This set of performance measures served as the primary basis for designing the new GWTG–S program, along with considerations of feasibility for collecting data on these measures, Dr. Sheth said in an interview. “We hope to make it easy” for centers to collect the data needed to participate.
The existing GWTG–S program is now 17-years old, and has spread to nearly 2,400 U.S. stroke centers as of early 2020, but the time has come to broaden its reach to patients with ICH and the programs that treat these patients, Dr. Sheth said. After years of nihilism about the prospects for patients following an ICH stroke, survival rates have increased, presenting “an opportunity to optimize care, for quality improvement,” he explained. “It’s a huge shift.” ICH patients “do better than we used to think.”
The Get With the Guidelines – Stroke program is finally turning its attention to hemorrhagic strokes after having spurred improved patient management performance from participating U.S. stroke centers since its start in 2003 with a focus on acute ischemic stroke.
The advisers who craft policy for Get With the Guidelines – Stroke (GWTG–S) are planning to launch a pilot program later in 2020 that will initiate data monitoring and quality improvement aimed at optimizing care for patients following an intracerebral hemorrhage (ICH) starting at 15 U.S. stroke centers, with announcement of these 15 participating centers expected later in 2020. The program will start by targeting nine specific, evidence-based, key aspects of the acute management of ICH patients, said Kevin N. Sheth, MD, professor of neurology and neurosurgery, and chief of neurocritical care and emergency neurology at Yale University in New Haven, Conn, and a volunteer expert who is part of the team developing the ICH initiative.
According to Dr. Sheth, the nine imperatives of acute ICH care that the program plans to monitor at participating centers are:
- Obtain a baseline severity score.
- Identify etiology as spontaneous or treatment related.
- Perform coagulopathy reversal or anticoagulant reversal.
- Administer venous thromboembolism prophylaxis.
- Apply dysphagia screening within 24 hours, and delay oral intake until patient passes dysphagia screen.
- Provide patient management in a multidisciplinary stroke or ICU unit.
- Prescribe appropriate blood pressure treatment at discharge.
- Perform assessment for rehabilitation.
- Avoid prescribing corticosteroids and other contraindicated drugs.
GWTG–S is adopting these metrics for assessing the acute care of ICH patients based largely on the recommendations of an expert 2018 panel organized by the American Heart Association and American Stroke. Association that proposed a set of performance measures for the care of ICH patients. This set of performance measures served as the primary basis for designing the new GWTG–S program, along with considerations of feasibility for collecting data on these measures, Dr. Sheth said in an interview. “We hope to make it easy” for centers to collect the data needed to participate.
The existing GWTG–S program is now 17-years old, and has spread to nearly 2,400 U.S. stroke centers as of early 2020, but the time has come to broaden its reach to patients with ICH and the programs that treat these patients, Dr. Sheth said. After years of nihilism about the prospects for patients following an ICH stroke, survival rates have increased, presenting “an opportunity to optimize care, for quality improvement,” he explained. “It’s a huge shift.” ICH patients “do better than we used to think.”
Recent treatment advances brighten prospects for intracerebral hemorrhage patients
LOS ANGELES – Intracerebral hemorrhage (ICH) appears to be not nearly as uniformly devastating to patients as its reputation suggests. Recent study results documented unexpectedly decent recovery prospects for hemorrhagic stroke patients assessed after 1 year who were earlier considered moderately severe or severely disabled based on their 30-day status. And these data provide further support for the growing impression among clinicians that a way forward for improving outcomes even more is with a “gentle” surgical intervention designed to substantially reduce ICH clot volume.
“Historically, there’s been a lot of nihilism around these patients. Intracerebral hemorrhage has always been the deadliest stroke type, but one of the great advances of the past 10-20 years is that ICH survival has improved. Patients do better than we used to think,” said Kevin N. Sheth, MD, professor of neurology and neurosurgery, and chief of neurocritical care and emergency neurology at Yale University in New Haven, Conn. “Even though ICH remains a difficult disease, this change has two big implications,” Dr. Sheth said in an interview during the International Stroke Conference sponsored by the American Heart Association. First, increased ICH survival offers an opportunity to expand the reach of recent management advances through quality improvement programs that emphasize new strategies that work better and incentivize delivery of these successful strategies to more patients.
The second implication is simply a growing number of ICH survivors, expanding the population of patients who stand to gain from these new management strategies. Dr. Sheth is working with the Get With the Guidelines – Stroke program, a quality-improvement program begun in 2003 and until now aimed at patients with acute ischemic stroke, to develop a 15-site pilot program planned to start in 2020 that will begin implementing and studying a Get With the Guidelines – Stroke quality-improvement program focused on patients with an ICH. The current conception of a quality measurement and improvement program like Get with the Guidelines – Stroke for patients with ICH stems from an important, earlier milestone in the emergence of effective ICH treatments, the 2018 publication of performance measures for ICH care that identified nine key management steps for assessing quality of care and documented the evidence behind them.
“Evidence for optimal treatment of ICH has lagged behind that for ischemic stroke, and consequently, metrics specific to ICH care have not been widely promulgated,” said the authors of the 2018 ICH performance measures, a panel that included Dr. Sheth. “However, numerous more recent studies and clinical trials of various medical and surgical interventions for ICH have been published and form the basis of evidence-based guidelines for the management of ICH,” they explained.
MISTIE III showcases better ICH outcomes
Perhaps the most dramatic recent evidence of brighter prospects for ICH patients came in data collected during the MISTIE III (Minimally Invasive Surgery with Thrombolysis in Intracerebral Hemorrhage Evacuation III) trial, which randomized 506 ICH patients with a hematoma of at least 30 mL to standard care or to a “gentle” clot-reduction protocol using a small-bore catheter placed with stereotactic guidance to both evacuate clot and introduce a serial infusion of alteplase into the clot to try to shrink its volume to less than 15 mL. The study’s results showed a neutral effect for the primary outcome, the incidence of recovery to a modified Rankin Scale (mRS) score of 0-3 at 1 year after entry, which occurred in 45% of the surgically treated patients and 41% of the controls in a modified intention-to-treat analysis that included 499 of the randomized patients, a difference that did not reach statistical significance.
However, when the analysis focused on the 146 of 247 patients (59%) randomized to surgical plus lytic intervention who underwent the procedure and actually had their clot volume reduced to 15 mL or less per protocol, the adjusted incidence of the primary endpoint was double that of patients who underwent the procedure but failed to have their residual clot reduced to this size. A similar doubling of good outcomes occurred when MISTIE patients had their residual clot cut to 20 mL or less, compared with those who didn’t reach this, with the differences in both analyses statistically significant. The actual rates showed patients with clot cut to 15 mL or less having a 53% rate of a mRS score of 0-3 after 1 year, compared with 33% of patients who received the intervention but had their residual clot remain above 15 mL.
The MISTIE III investigators looked at their data to try to get better insight into the outcome of all “poor prognosis” patients in the study regardless of their treatment arm assignment, and how patients and their family members made decisions for withdrawal of life-sustaining therapy. In MISTIE III, 61 patients had withdrawal of life-sustaining treatment (WoLST), with more than 40% of the WoLST occurring with patients randomized to the intervention arm including 10 patients treated to a residual clot volume of 15 mL or less. To quantify the disease severity in these 61 patients, the researchers applied a six-item formula at 30 days after the stroke, a metric their 2019 report described in detail. They then used these severity scores to identify 104 matched patients who were alive at 30 days and remained on life-sustaining treatment to see their 1-year outcomes. At 30 days, the 104 matched patients included 82 (79%) with a mRS score of 5 (severe disability) and 22 patients (21%) with a mRS score of 4 (moderately severe disability). Overall, an mRS score of 4 or 5 was quite prevalent 30 days after the stroke, with 87% of the patients treated with the MISTIE intervention and 90% of the control patients having this degree of disability at 30 days.
When the MISTIE III investigators followed these patients for a year, they made an unexpected finding: A substantial incidence of patients whose condition had improved since day 30. One year out, 40 (39%) of these 104 patients had improved to a mRS score of 1-3, including 10 (10%) with a mRS score of 1 or 2. Another indicator of the reasonable outcome many of these patients achieved was that after 1 year 69% were living at home.
“Our data show that many ICH subjects with clinical factors that suggest ‘poor prognosis,’ when given time, can achieve a favorable outcome and return home,” concluded Noeleen Ostapkovich, who presented these results at the Stroke Conference.
She cited these findings as potentially helpful for refining the information given to patients and families on the prognosis for ICH patients at about 30 days after their event, the usual time for assessment. “These patients looked like they weren’t going to do well after 30 days, but by 365 days they had improved physically and in their ability to care for themselves at home,” noted Ms. Ostapkovich, a researcher in the Brain Injury Outcomes Clinical Trial Coordinating Center of Johns Hopkins University in Baltimore.
A message for acute-care clinicians
She and her colleagues highlighted the implications these new findings have for clinical decision making in the first weeks after an ICH.
“Acute-care physicians see these patients at day 30, not at day 365, so it’s important that they have a clear picture of what these patients could look like a year later. It’s an important message,” Ms. Ostapkovich said in an interview.
In fact, a colleague of hers at Johns Hopkins ran an analysis that looked at factors that contributed to families opting for WoLST for 61 of the MISTIE III patients, and found that 38 family groups (62%) cited the anticipated outcome of the patient in a dependent state as their primary reason for opting for WoLST, Lourdes J. Carhuapoma reported in a separate talk at the conference.
“The main message is that many patients with significant ICH did well and recovered despite having very poor prognostic factors at 30 days, but it took more time. A concern is that the [prognostic] information families receive may be wrong. There is a disconnect,” between what families get told to expect and what actually happens, said Ms. Carhuapoma, an acute care nurse practitioner at Johns Hopkins.
“When physicians, nurses, and family members get together” to discuss ICH patients like these after 30 days, “they see the glass as empty. But the real message is that the glass is half full,” summed up Daniel F. Hanley, MD, lead investigator of MISTIE III and professor of neurology at Johns Hopkins. “These data show a large amount of improvement between 30 and 180 days.” The 104 patients with exclusively mRS scores of 4 or 5 at day 30 had a 30% incidence of improvement to an mRS score of 2 or 3 after 180 days, on their way to a 39% rate of mRS scores of 1-3 at 1 year.
An additional analysis that has not yet been presented showed that the “strongest predictor” of whether or not patients who presented with a mRS score of 4 or 5 after 30 days improved their status at 1 year was if their residual hematoma volume shrank to 15 mL or less, Dr. Hanley said in an interview. “It’s not rocket science. If you had to choose between a 45-mL hematoma and less than 15 mL, which would you choose? What’s new here is how this recovery can play out,” taking 180 days or longer in some patients to become apparent.
More evidence needed to prove MISTIE’s hypothesis
According to Dr. Hanley, the MISTIE III findings have begun to influence practice despite its neutral primary finding, with more attention being paid to reducing residual clot volume following an ICH. And evidence continues to mount that more aggressive minimization of hematoma size can have an important effect on outcomes. For example, another study presented at the conference assessed the incremental change in prognostic accuracy when the ICH score, a five-item formula for estimating the prognosis of an ICH patient, substituted a precise quantification of residual hematoma volume rather than the original, dichotomous entry for either a hematoma volume of 30 mL or greater, or less than 30 mL, and when the severity score also quantified intraventricular hemorrhage (IVH) volume rather than simply designating IVH as present or absent.
Using data from 933 patients who had been enrolled in either MISTIE III or in another study of hematoma volume reduction, CLEAR III, the analysis showed that including specific quantification of both residual ICH volume as well as residual IVH volume improved the area under the receiver operating characteristic curve of the ICH score as a prognostic assessment from 0.70 to 0.75 in the intervention arms of the two trials, and from 0.60 to 0.68 in the two combined control arms, Adam de Havenon, MD, reported in a talk at the conference. “These data show that quantifying ICH and IVH volume improves mortality prognostication,” concluded Dr. de Havenon, a vascular and stroke neurologist at the University of Utah in Salt Lake City.
Furthermore, it’s “certainly evidence for the importance of volume reduction,” he said during discussion of his talk. “The MISTIE procedure can reset patients” so that their outcomes become more like patients with much smaller clot volumes even if they start with large hematomas. “In our experience, if the volume is reduced to 5 mL, there is real benefit regardless of how big the clot was initially,” Dr. de Havenon said.
But the neutral result for the MISTIE III primary endpoint will, for the time being, hobble application of this concept and keep the MISTIE intervention from rising to a level I recommendation until greater evidence for its efficacy comes out.
“It’s been known for many years that clot size matters when it comes to ICH. The MISTIE team has made a very compelling case that [reducing clot volume] is a very reasonable hypothesis, but we must continue to acquire data that can confirm it,” Dr. Sheth commented.
Dr. Sheth’s institution receives research funding from Novartis and Bard for studies that Dr. Sheth helps run. The MISTIE III study received the alteplase used in the study at no cost from Genentech. Ms. Ostapkovich and Ms. Carhuapoma had no disclosures. Dr. Hanley has received personal fees from BrainScope, Medtronic, Neurotrope, Op2Lysis, and Portola. Dr. de Havenon has received research funding from Regeneron.
LOS ANGELES – Intracerebral hemorrhage (ICH) appears to be not nearly as uniformly devastating to patients as its reputation suggests. Recent study results documented unexpectedly decent recovery prospects for hemorrhagic stroke patients assessed after 1 year who were earlier considered moderately severe or severely disabled based on their 30-day status. And these data provide further support for the growing impression among clinicians that a way forward for improving outcomes even more is with a “gentle” surgical intervention designed to substantially reduce ICH clot volume.
“Historically, there’s been a lot of nihilism around these patients. Intracerebral hemorrhage has always been the deadliest stroke type, but one of the great advances of the past 10-20 years is that ICH survival has improved. Patients do better than we used to think,” said Kevin N. Sheth, MD, professor of neurology and neurosurgery, and chief of neurocritical care and emergency neurology at Yale University in New Haven, Conn. “Even though ICH remains a difficult disease, this change has two big implications,” Dr. Sheth said in an interview during the International Stroke Conference sponsored by the American Heart Association. First, increased ICH survival offers an opportunity to expand the reach of recent management advances through quality improvement programs that emphasize new strategies that work better and incentivize delivery of these successful strategies to more patients.
The second implication is simply a growing number of ICH survivors, expanding the population of patients who stand to gain from these new management strategies. Dr. Sheth is working with the Get With the Guidelines – Stroke program, a quality-improvement program begun in 2003 and until now aimed at patients with acute ischemic stroke, to develop a 15-site pilot program planned to start in 2020 that will begin implementing and studying a Get With the Guidelines – Stroke quality-improvement program focused on patients with an ICH. The current conception of a quality measurement and improvement program like Get with the Guidelines – Stroke for patients with ICH stems from an important, earlier milestone in the emergence of effective ICH treatments, the 2018 publication of performance measures for ICH care that identified nine key management steps for assessing quality of care and documented the evidence behind them.
“Evidence for optimal treatment of ICH has lagged behind that for ischemic stroke, and consequently, metrics specific to ICH care have not been widely promulgated,” said the authors of the 2018 ICH performance measures, a panel that included Dr. Sheth. “However, numerous more recent studies and clinical trials of various medical and surgical interventions for ICH have been published and form the basis of evidence-based guidelines for the management of ICH,” they explained.
MISTIE III showcases better ICH outcomes
Perhaps the most dramatic recent evidence of brighter prospects for ICH patients came in data collected during the MISTIE III (Minimally Invasive Surgery with Thrombolysis in Intracerebral Hemorrhage Evacuation III) trial, which randomized 506 ICH patients with a hematoma of at least 30 mL to standard care or to a “gentle” clot-reduction protocol using a small-bore catheter placed with stereotactic guidance to both evacuate clot and introduce a serial infusion of alteplase into the clot to try to shrink its volume to less than 15 mL. The study’s results showed a neutral effect for the primary outcome, the incidence of recovery to a modified Rankin Scale (mRS) score of 0-3 at 1 year after entry, which occurred in 45% of the surgically treated patients and 41% of the controls in a modified intention-to-treat analysis that included 499 of the randomized patients, a difference that did not reach statistical significance.
However, when the analysis focused on the 146 of 247 patients (59%) randomized to surgical plus lytic intervention who underwent the procedure and actually had their clot volume reduced to 15 mL or less per protocol, the adjusted incidence of the primary endpoint was double that of patients who underwent the procedure but failed to have their residual clot reduced to this size. A similar doubling of good outcomes occurred when MISTIE patients had their residual clot cut to 20 mL or less, compared with those who didn’t reach this, with the differences in both analyses statistically significant. The actual rates showed patients with clot cut to 15 mL or less having a 53% rate of a mRS score of 0-3 after 1 year, compared with 33% of patients who received the intervention but had their residual clot remain above 15 mL.
The MISTIE III investigators looked at their data to try to get better insight into the outcome of all “poor prognosis” patients in the study regardless of their treatment arm assignment, and how patients and their family members made decisions for withdrawal of life-sustaining therapy. In MISTIE III, 61 patients had withdrawal of life-sustaining treatment (WoLST), with more than 40% of the WoLST occurring with patients randomized to the intervention arm including 10 patients treated to a residual clot volume of 15 mL or less. To quantify the disease severity in these 61 patients, the researchers applied a six-item formula at 30 days after the stroke, a metric their 2019 report described in detail. They then used these severity scores to identify 104 matched patients who were alive at 30 days and remained on life-sustaining treatment to see their 1-year outcomes. At 30 days, the 104 matched patients included 82 (79%) with a mRS score of 5 (severe disability) and 22 patients (21%) with a mRS score of 4 (moderately severe disability). Overall, an mRS score of 4 or 5 was quite prevalent 30 days after the stroke, with 87% of the patients treated with the MISTIE intervention and 90% of the control patients having this degree of disability at 30 days.
When the MISTIE III investigators followed these patients for a year, they made an unexpected finding: A substantial incidence of patients whose condition had improved since day 30. One year out, 40 (39%) of these 104 patients had improved to a mRS score of 1-3, including 10 (10%) with a mRS score of 1 or 2. Another indicator of the reasonable outcome many of these patients achieved was that after 1 year 69% were living at home.
“Our data show that many ICH subjects with clinical factors that suggest ‘poor prognosis,’ when given time, can achieve a favorable outcome and return home,” concluded Noeleen Ostapkovich, who presented these results at the Stroke Conference.
She cited these findings as potentially helpful for refining the information given to patients and families on the prognosis for ICH patients at about 30 days after their event, the usual time for assessment. “These patients looked like they weren’t going to do well after 30 days, but by 365 days they had improved physically and in their ability to care for themselves at home,” noted Ms. Ostapkovich, a researcher in the Brain Injury Outcomes Clinical Trial Coordinating Center of Johns Hopkins University in Baltimore.
A message for acute-care clinicians
She and her colleagues highlighted the implications these new findings have for clinical decision making in the first weeks after an ICH.
“Acute-care physicians see these patients at day 30, not at day 365, so it’s important that they have a clear picture of what these patients could look like a year later. It’s an important message,” Ms. Ostapkovich said in an interview.
In fact, a colleague of hers at Johns Hopkins ran an analysis that looked at factors that contributed to families opting for WoLST for 61 of the MISTIE III patients, and found that 38 family groups (62%) cited the anticipated outcome of the patient in a dependent state as their primary reason for opting for WoLST, Lourdes J. Carhuapoma reported in a separate talk at the conference.
“The main message is that many patients with significant ICH did well and recovered despite having very poor prognostic factors at 30 days, but it took more time. A concern is that the [prognostic] information families receive may be wrong. There is a disconnect,” between what families get told to expect and what actually happens, said Ms. Carhuapoma, an acute care nurse practitioner at Johns Hopkins.
“When physicians, nurses, and family members get together” to discuss ICH patients like these after 30 days, “they see the glass as empty. But the real message is that the glass is half full,” summed up Daniel F. Hanley, MD, lead investigator of MISTIE III and professor of neurology at Johns Hopkins. “These data show a large amount of improvement between 30 and 180 days.” The 104 patients with exclusively mRS scores of 4 or 5 at day 30 had a 30% incidence of improvement to an mRS score of 2 or 3 after 180 days, on their way to a 39% rate of mRS scores of 1-3 at 1 year.
An additional analysis that has not yet been presented showed that the “strongest predictor” of whether or not patients who presented with a mRS score of 4 or 5 after 30 days improved their status at 1 year was if their residual hematoma volume shrank to 15 mL or less, Dr. Hanley said in an interview. “It’s not rocket science. If you had to choose between a 45-mL hematoma and less than 15 mL, which would you choose? What’s new here is how this recovery can play out,” taking 180 days or longer in some patients to become apparent.
More evidence needed to prove MISTIE’s hypothesis
According to Dr. Hanley, the MISTIE III findings have begun to influence practice despite its neutral primary finding, with more attention being paid to reducing residual clot volume following an ICH. And evidence continues to mount that more aggressive minimization of hematoma size can have an important effect on outcomes. For example, another study presented at the conference assessed the incremental change in prognostic accuracy when the ICH score, a five-item formula for estimating the prognosis of an ICH patient, substituted a precise quantification of residual hematoma volume rather than the original, dichotomous entry for either a hematoma volume of 30 mL or greater, or less than 30 mL, and when the severity score also quantified intraventricular hemorrhage (IVH) volume rather than simply designating IVH as present or absent.
Using data from 933 patients who had been enrolled in either MISTIE III or in another study of hematoma volume reduction, CLEAR III, the analysis showed that including specific quantification of both residual ICH volume as well as residual IVH volume improved the area under the receiver operating characteristic curve of the ICH score as a prognostic assessment from 0.70 to 0.75 in the intervention arms of the two trials, and from 0.60 to 0.68 in the two combined control arms, Adam de Havenon, MD, reported in a talk at the conference. “These data show that quantifying ICH and IVH volume improves mortality prognostication,” concluded Dr. de Havenon, a vascular and stroke neurologist at the University of Utah in Salt Lake City.
Furthermore, it’s “certainly evidence for the importance of volume reduction,” he said during discussion of his talk. “The MISTIE procedure can reset patients” so that their outcomes become more like patients with much smaller clot volumes even if they start with large hematomas. “In our experience, if the volume is reduced to 5 mL, there is real benefit regardless of how big the clot was initially,” Dr. de Havenon said.
But the neutral result for the MISTIE III primary endpoint will, for the time being, hobble application of this concept and keep the MISTIE intervention from rising to a level I recommendation until greater evidence for its efficacy comes out.
“It’s been known for many years that clot size matters when it comes to ICH. The MISTIE team has made a very compelling case that [reducing clot volume] is a very reasonable hypothesis, but we must continue to acquire data that can confirm it,” Dr. Sheth commented.
Dr. Sheth’s institution receives research funding from Novartis and Bard for studies that Dr. Sheth helps run. The MISTIE III study received the alteplase used in the study at no cost from Genentech. Ms. Ostapkovich and Ms. Carhuapoma had no disclosures. Dr. Hanley has received personal fees from BrainScope, Medtronic, Neurotrope, Op2Lysis, and Portola. Dr. de Havenon has received research funding from Regeneron.
LOS ANGELES – Intracerebral hemorrhage (ICH) appears to be not nearly as uniformly devastating to patients as its reputation suggests. Recent study results documented unexpectedly decent recovery prospects for hemorrhagic stroke patients assessed after 1 year who were earlier considered moderately severe or severely disabled based on their 30-day status. And these data provide further support for the growing impression among clinicians that a way forward for improving outcomes even more is with a “gentle” surgical intervention designed to substantially reduce ICH clot volume.
“Historically, there’s been a lot of nihilism around these patients. Intracerebral hemorrhage has always been the deadliest stroke type, but one of the great advances of the past 10-20 years is that ICH survival has improved. Patients do better than we used to think,” said Kevin N. Sheth, MD, professor of neurology and neurosurgery, and chief of neurocritical care and emergency neurology at Yale University in New Haven, Conn. “Even though ICH remains a difficult disease, this change has two big implications,” Dr. Sheth said in an interview during the International Stroke Conference sponsored by the American Heart Association. First, increased ICH survival offers an opportunity to expand the reach of recent management advances through quality improvement programs that emphasize new strategies that work better and incentivize delivery of these successful strategies to more patients.
The second implication is simply a growing number of ICH survivors, expanding the population of patients who stand to gain from these new management strategies. Dr. Sheth is working with the Get With the Guidelines – Stroke program, a quality-improvement program begun in 2003 and until now aimed at patients with acute ischemic stroke, to develop a 15-site pilot program planned to start in 2020 that will begin implementing and studying a Get With the Guidelines – Stroke quality-improvement program focused on patients with an ICH. The current conception of a quality measurement and improvement program like Get with the Guidelines – Stroke for patients with ICH stems from an important, earlier milestone in the emergence of effective ICH treatments, the 2018 publication of performance measures for ICH care that identified nine key management steps for assessing quality of care and documented the evidence behind them.
“Evidence for optimal treatment of ICH has lagged behind that for ischemic stroke, and consequently, metrics specific to ICH care have not been widely promulgated,” said the authors of the 2018 ICH performance measures, a panel that included Dr. Sheth. “However, numerous more recent studies and clinical trials of various medical and surgical interventions for ICH have been published and form the basis of evidence-based guidelines for the management of ICH,” they explained.
MISTIE III showcases better ICH outcomes
Perhaps the most dramatic recent evidence of brighter prospects for ICH patients came in data collected during the MISTIE III (Minimally Invasive Surgery with Thrombolysis in Intracerebral Hemorrhage Evacuation III) trial, which randomized 506 ICH patients with a hematoma of at least 30 mL to standard care or to a “gentle” clot-reduction protocol using a small-bore catheter placed with stereotactic guidance to both evacuate clot and introduce a serial infusion of alteplase into the clot to try to shrink its volume to less than 15 mL. The study’s results showed a neutral effect for the primary outcome, the incidence of recovery to a modified Rankin Scale (mRS) score of 0-3 at 1 year after entry, which occurred in 45% of the surgically treated patients and 41% of the controls in a modified intention-to-treat analysis that included 499 of the randomized patients, a difference that did not reach statistical significance.
However, when the analysis focused on the 146 of 247 patients (59%) randomized to surgical plus lytic intervention who underwent the procedure and actually had their clot volume reduced to 15 mL or less per protocol, the adjusted incidence of the primary endpoint was double that of patients who underwent the procedure but failed to have their residual clot reduced to this size. A similar doubling of good outcomes occurred when MISTIE patients had their residual clot cut to 20 mL or less, compared with those who didn’t reach this, with the differences in both analyses statistically significant. The actual rates showed patients with clot cut to 15 mL or less having a 53% rate of a mRS score of 0-3 after 1 year, compared with 33% of patients who received the intervention but had their residual clot remain above 15 mL.
The MISTIE III investigators looked at their data to try to get better insight into the outcome of all “poor prognosis” patients in the study regardless of their treatment arm assignment, and how patients and their family members made decisions for withdrawal of life-sustaining therapy. In MISTIE III, 61 patients had withdrawal of life-sustaining treatment (WoLST), with more than 40% of the WoLST occurring with patients randomized to the intervention arm including 10 patients treated to a residual clot volume of 15 mL or less. To quantify the disease severity in these 61 patients, the researchers applied a six-item formula at 30 days after the stroke, a metric their 2019 report described in detail. They then used these severity scores to identify 104 matched patients who were alive at 30 days and remained on life-sustaining treatment to see their 1-year outcomes. At 30 days, the 104 matched patients included 82 (79%) with a mRS score of 5 (severe disability) and 22 patients (21%) with a mRS score of 4 (moderately severe disability). Overall, an mRS score of 4 or 5 was quite prevalent 30 days after the stroke, with 87% of the patients treated with the MISTIE intervention and 90% of the control patients having this degree of disability at 30 days.
When the MISTIE III investigators followed these patients for a year, they made an unexpected finding: A substantial incidence of patients whose condition had improved since day 30. One year out, 40 (39%) of these 104 patients had improved to a mRS score of 1-3, including 10 (10%) with a mRS score of 1 or 2. Another indicator of the reasonable outcome many of these patients achieved was that after 1 year 69% were living at home.
“Our data show that many ICH subjects with clinical factors that suggest ‘poor prognosis,’ when given time, can achieve a favorable outcome and return home,” concluded Noeleen Ostapkovich, who presented these results at the Stroke Conference.
She cited these findings as potentially helpful for refining the information given to patients and families on the prognosis for ICH patients at about 30 days after their event, the usual time for assessment. “These patients looked like they weren’t going to do well after 30 days, but by 365 days they had improved physically and in their ability to care for themselves at home,” noted Ms. Ostapkovich, a researcher in the Brain Injury Outcomes Clinical Trial Coordinating Center of Johns Hopkins University in Baltimore.
A message for acute-care clinicians
She and her colleagues highlighted the implications these new findings have for clinical decision making in the first weeks after an ICH.
“Acute-care physicians see these patients at day 30, not at day 365, so it’s important that they have a clear picture of what these patients could look like a year later. It’s an important message,” Ms. Ostapkovich said in an interview.
In fact, a colleague of hers at Johns Hopkins ran an analysis that looked at factors that contributed to families opting for WoLST for 61 of the MISTIE III patients, and found that 38 family groups (62%) cited the anticipated outcome of the patient in a dependent state as their primary reason for opting for WoLST, Lourdes J. Carhuapoma reported in a separate talk at the conference.
“The main message is that many patients with significant ICH did well and recovered despite having very poor prognostic factors at 30 days, but it took more time. A concern is that the [prognostic] information families receive may be wrong. There is a disconnect,” between what families get told to expect and what actually happens, said Ms. Carhuapoma, an acute care nurse practitioner at Johns Hopkins.
“When physicians, nurses, and family members get together” to discuss ICH patients like these after 30 days, “they see the glass as empty. But the real message is that the glass is half full,” summed up Daniel F. Hanley, MD, lead investigator of MISTIE III and professor of neurology at Johns Hopkins. “These data show a large amount of improvement between 30 and 180 days.” The 104 patients with exclusively mRS scores of 4 or 5 at day 30 had a 30% incidence of improvement to an mRS score of 2 or 3 after 180 days, on their way to a 39% rate of mRS scores of 1-3 at 1 year.
An additional analysis that has not yet been presented showed that the “strongest predictor” of whether or not patients who presented with a mRS score of 4 or 5 after 30 days improved their status at 1 year was if their residual hematoma volume shrank to 15 mL or less, Dr. Hanley said in an interview. “It’s not rocket science. If you had to choose between a 45-mL hematoma and less than 15 mL, which would you choose? What’s new here is how this recovery can play out,” taking 180 days or longer in some patients to become apparent.
More evidence needed to prove MISTIE’s hypothesis
According to Dr. Hanley, the MISTIE III findings have begun to influence practice despite its neutral primary finding, with more attention being paid to reducing residual clot volume following an ICH. And evidence continues to mount that more aggressive minimization of hematoma size can have an important effect on outcomes. For example, another study presented at the conference assessed the incremental change in prognostic accuracy when the ICH score, a five-item formula for estimating the prognosis of an ICH patient, substituted a precise quantification of residual hematoma volume rather than the original, dichotomous entry for either a hematoma volume of 30 mL or greater, or less than 30 mL, and when the severity score also quantified intraventricular hemorrhage (IVH) volume rather than simply designating IVH as present or absent.
Using data from 933 patients who had been enrolled in either MISTIE III or in another study of hematoma volume reduction, CLEAR III, the analysis showed that including specific quantification of both residual ICH volume as well as residual IVH volume improved the area under the receiver operating characteristic curve of the ICH score as a prognostic assessment from 0.70 to 0.75 in the intervention arms of the two trials, and from 0.60 to 0.68 in the two combined control arms, Adam de Havenon, MD, reported in a talk at the conference. “These data show that quantifying ICH and IVH volume improves mortality prognostication,” concluded Dr. de Havenon, a vascular and stroke neurologist at the University of Utah in Salt Lake City.
Furthermore, it’s “certainly evidence for the importance of volume reduction,” he said during discussion of his talk. “The MISTIE procedure can reset patients” so that their outcomes become more like patients with much smaller clot volumes even if they start with large hematomas. “In our experience, if the volume is reduced to 5 mL, there is real benefit regardless of how big the clot was initially,” Dr. de Havenon said.
But the neutral result for the MISTIE III primary endpoint will, for the time being, hobble application of this concept and keep the MISTIE intervention from rising to a level I recommendation until greater evidence for its efficacy comes out.
“It’s been known for many years that clot size matters when it comes to ICH. The MISTIE team has made a very compelling case that [reducing clot volume] is a very reasonable hypothesis, but we must continue to acquire data that can confirm it,” Dr. Sheth commented.
Dr. Sheth’s institution receives research funding from Novartis and Bard for studies that Dr. Sheth helps run. The MISTIE III study received the alteplase used in the study at no cost from Genentech. Ms. Ostapkovich and Ms. Carhuapoma had no disclosures. Dr. Hanley has received personal fees from BrainScope, Medtronic, Neurotrope, Op2Lysis, and Portola. Dr. de Havenon has received research funding from Regeneron.
REPORTING FROM ISC 2020
Researchers develop score to predict risk of stroke among migraineurs with aura
LOS ANGELES – The study on which the risk score is based was presented at the International Stroke Conference sponsored by the American Heart Association. Migraine with aura, for which younger women are at higher risk, increases the risk of ischemic stroke. “With our new risk-prediction tool, we could start identifying those at higher risk, treat their risk factors, and lower their risk of stroke,” said Souvik Sen, MD, MPH, professor and chair of neurology at the University of South Carolina in Columbia, in a press release.
Risk groups significantly discriminated stroke risk
To create the score, Dr. Sen and colleagues examined data from the ARIC (Atherosclerosis Risk in Communities) cohort, which includes community-dwelling people in Forsyth County, N.C.; Jackson, Miss.; Washington County, Md.; and the suburbs of Minneapolis. Researchers have been following the participants since 1987. From this population, Dr. Sen and colleagues identified 429 participants with a history of migraine with aura. Most of these participants were women aged 50-59 years at their first visit. The researchers analyzed the association between potential risk factors and ischemic stroke using Cox proportional hazards analysis.
Of the 429 participants, 31 had an ischemic stroke during a follow-up period of 20 years. Dr. Sen’s group created a risk score by identifying five risk factors for stroke and assigning them points in proportion to their influence (i.e., their regression coefficients). They assigned diabetes mellitus – 7 points; age older than 65 years – 5 points; heart rate variability (i.e., the standard deviation of all normal-to-normal RR intervals) – 3 points; hypertension – 3 points – and sex – 1 point. Then the researchers calculated risk scores for each patient and defined a low-risk group (from 0-4 points), a moderate-risk group (5-10 points), and a high-risk group (11-21 points).
After 18 years of follow-up, the incidence of stroke was 3% in the low-risk group, 8% in the moderate-risk group, and 34% in the high-risk group. The hazard ratio for ischemic stroke in the high-risk group, compared with the low-risk group, was 7.35. Kaplan Meier curves indicated that the risk-stratification groups significantly discriminated stroke risk among the sample. The risk score should be validated in an independent population cohort, said the investigators.
Dr. Sen and colleagues did not report any funding for this study. Investigators reported receiving grants from the National Institutes of Health, the American Heart Association, and the American Academy of Neurology.
Score may leave important variables unexamined
One mechanism through which migraine increases the risk of stroke is the constriction of blood vessels, said Louis R. Caplan, MD, professor of neurology at Harvard Medical School in Boston and member of the editorial advisory board of Neurology Reviews. Triptans, which many patients use to treat migraine, also cause vasoconstriction. In addition, migraine increases blood coagulation.
Although the risk score developed by Dr. Sen and colleagues accounts for various comorbidities, it may not apply equally to all patients. “As I understand it, they’re just using migraine with aura as a single factor,” said Dr. Caplan. Variables such as prolonged aura, frequent episodes, and aura-related deficit are associated with increased risk of stroke, but the risk score does not examine these factors.
Patients with severe, long-lasting attacks or attacks that involve weakness or aphasia should receive prophylactic treatment to prevent vasoconstriction, such as verapamil (Verelan), said Dr. Caplan. Antithrombotic agents such as aspirin also may be appropriate prophylaxis. Whether effective treatment of migraine with aura decreases the risk of stroke remains unknown.
SOURCE: Trivedi T et al. ISC 2020. Abstract WMP117.
LOS ANGELES – The study on which the risk score is based was presented at the International Stroke Conference sponsored by the American Heart Association. Migraine with aura, for which younger women are at higher risk, increases the risk of ischemic stroke. “With our new risk-prediction tool, we could start identifying those at higher risk, treat their risk factors, and lower their risk of stroke,” said Souvik Sen, MD, MPH, professor and chair of neurology at the University of South Carolina in Columbia, in a press release.
Risk groups significantly discriminated stroke risk
To create the score, Dr. Sen and colleagues examined data from the ARIC (Atherosclerosis Risk in Communities) cohort, which includes community-dwelling people in Forsyth County, N.C.; Jackson, Miss.; Washington County, Md.; and the suburbs of Minneapolis. Researchers have been following the participants since 1987. From this population, Dr. Sen and colleagues identified 429 participants with a history of migraine with aura. Most of these participants were women aged 50-59 years at their first visit. The researchers analyzed the association between potential risk factors and ischemic stroke using Cox proportional hazards analysis.
Of the 429 participants, 31 had an ischemic stroke during a follow-up period of 20 years. Dr. Sen’s group created a risk score by identifying five risk factors for stroke and assigning them points in proportion to their influence (i.e., their regression coefficients). They assigned diabetes mellitus – 7 points; age older than 65 years – 5 points; heart rate variability (i.e., the standard deviation of all normal-to-normal RR intervals) – 3 points; hypertension – 3 points – and sex – 1 point. Then the researchers calculated risk scores for each patient and defined a low-risk group (from 0-4 points), a moderate-risk group (5-10 points), and a high-risk group (11-21 points).
After 18 years of follow-up, the incidence of stroke was 3% in the low-risk group, 8% in the moderate-risk group, and 34% in the high-risk group. The hazard ratio for ischemic stroke in the high-risk group, compared with the low-risk group, was 7.35. Kaplan Meier curves indicated that the risk-stratification groups significantly discriminated stroke risk among the sample. The risk score should be validated in an independent population cohort, said the investigators.
Dr. Sen and colleagues did not report any funding for this study. Investigators reported receiving grants from the National Institutes of Health, the American Heart Association, and the American Academy of Neurology.
Score may leave important variables unexamined
One mechanism through which migraine increases the risk of stroke is the constriction of blood vessels, said Louis R. Caplan, MD, professor of neurology at Harvard Medical School in Boston and member of the editorial advisory board of Neurology Reviews. Triptans, which many patients use to treat migraine, also cause vasoconstriction. In addition, migraine increases blood coagulation.
Although the risk score developed by Dr. Sen and colleagues accounts for various comorbidities, it may not apply equally to all patients. “As I understand it, they’re just using migraine with aura as a single factor,” said Dr. Caplan. Variables such as prolonged aura, frequent episodes, and aura-related deficit are associated with increased risk of stroke, but the risk score does not examine these factors.
Patients with severe, long-lasting attacks or attacks that involve weakness or aphasia should receive prophylactic treatment to prevent vasoconstriction, such as verapamil (Verelan), said Dr. Caplan. Antithrombotic agents such as aspirin also may be appropriate prophylaxis. Whether effective treatment of migraine with aura decreases the risk of stroke remains unknown.
SOURCE: Trivedi T et al. ISC 2020. Abstract WMP117.
LOS ANGELES – The study on which the risk score is based was presented at the International Stroke Conference sponsored by the American Heart Association. Migraine with aura, for which younger women are at higher risk, increases the risk of ischemic stroke. “With our new risk-prediction tool, we could start identifying those at higher risk, treat their risk factors, and lower their risk of stroke,” said Souvik Sen, MD, MPH, professor and chair of neurology at the University of South Carolina in Columbia, in a press release.
Risk groups significantly discriminated stroke risk
To create the score, Dr. Sen and colleagues examined data from the ARIC (Atherosclerosis Risk in Communities) cohort, which includes community-dwelling people in Forsyth County, N.C.; Jackson, Miss.; Washington County, Md.; and the suburbs of Minneapolis. Researchers have been following the participants since 1987. From this population, Dr. Sen and colleagues identified 429 participants with a history of migraine with aura. Most of these participants were women aged 50-59 years at their first visit. The researchers analyzed the association between potential risk factors and ischemic stroke using Cox proportional hazards analysis.
Of the 429 participants, 31 had an ischemic stroke during a follow-up period of 20 years. Dr. Sen’s group created a risk score by identifying five risk factors for stroke and assigning them points in proportion to their influence (i.e., their regression coefficients). They assigned diabetes mellitus – 7 points; age older than 65 years – 5 points; heart rate variability (i.e., the standard deviation of all normal-to-normal RR intervals) – 3 points; hypertension – 3 points – and sex – 1 point. Then the researchers calculated risk scores for each patient and defined a low-risk group (from 0-4 points), a moderate-risk group (5-10 points), and a high-risk group (11-21 points).
After 18 years of follow-up, the incidence of stroke was 3% in the low-risk group, 8% in the moderate-risk group, and 34% in the high-risk group. The hazard ratio for ischemic stroke in the high-risk group, compared with the low-risk group, was 7.35. Kaplan Meier curves indicated that the risk-stratification groups significantly discriminated stroke risk among the sample. The risk score should be validated in an independent population cohort, said the investigators.
Dr. Sen and colleagues did not report any funding for this study. Investigators reported receiving grants from the National Institutes of Health, the American Heart Association, and the American Academy of Neurology.
Score may leave important variables unexamined
One mechanism through which migraine increases the risk of stroke is the constriction of blood vessels, said Louis R. Caplan, MD, professor of neurology at Harvard Medical School in Boston and member of the editorial advisory board of Neurology Reviews. Triptans, which many patients use to treat migraine, also cause vasoconstriction. In addition, migraine increases blood coagulation.
Although the risk score developed by Dr. Sen and colleagues accounts for various comorbidities, it may not apply equally to all patients. “As I understand it, they’re just using migraine with aura as a single factor,” said Dr. Caplan. Variables such as prolonged aura, frequent episodes, and aura-related deficit are associated with increased risk of stroke, but the risk score does not examine these factors.
Patients with severe, long-lasting attacks or attacks that involve weakness or aphasia should receive prophylactic treatment to prevent vasoconstriction, such as verapamil (Verelan), said Dr. Caplan. Antithrombotic agents such as aspirin also may be appropriate prophylaxis. Whether effective treatment of migraine with aura decreases the risk of stroke remains unknown.
SOURCE: Trivedi T et al. ISC 2020. Abstract WMP117.
REPORTING FROM ISC 2020