User login
Tranexamic Acid May Benefit Patients With Stroke
Patients with intracerebral hemorrhage may benefit from receiving a drug currently used to treat blood loss from major trauma and bleeding after childbirth, according to an international trial.
The study, led by experts at the University of Nottingham in the United Kingdom and funded by the National Institute for Health Research (NIHR) Health Technology Assessment Program, found that giving tranexamic acid to people who had had intracerebral hemorrhage reduced the number of deaths in the early days following the stroke. It also found that the amount of bleeding in the brain and number of associated serious complications were lower in the patients who had received tranexamic acid treatment.
However, the investigators found no difference in the number of people who were left disabled or had died at three months after their stroke (ie, the study’s primary outcome). The researchers believe that further study is needed on larger groups of patients to enable them to fully understand the potential benefits.
Nikola Sprigg, MD, Professor of Stroke Medicine at the Stroke Trials Unit in the university’s Division of Clinical Neuroscience, led the trial. “Tranexamic acid is cheap, costing less than £15 per patient, and widely available, so it has the potential for reducing death and disability across the world,” she said.
“While we failed to show significant benefits three months after stroke, the reduction in early deaths, amount of bleeding on the brain, and serious complications are signs that this drug may be of benefit in the future. More trials are needed, particularly focusing on giving treatment as soon as possible after the start of bleeding in this emergency condition,” Dr. Sprigg added.
Approximately 15% of all strokes in the UK—affecting around 22,000 people every year—are hemorrhagic and lead to permanent damage. While all people with acute stroke benefit from treatment on a stroke unit, there is currently no specific treatment for hemorrhagic stroke. Many people with hemorrhagic stroke die within a few days. Those who do survive are often left with debilitating disabilities, including paralysis and an inability to speak.
A previous small pilot study by the University of Nottingham and funded by the university and the Stroke Association concluded that a larger study was needed to accurately assess the effectiveness of tranexamic acid. The drug was chosen for the study after previous research showed that it was successful in stopping bleeding in people involved in car accidents.
For the latest trial, people who were diagnosed with bleeding on the brain, confirmed by CT scan, were offered the chance to take part in the study. When the person was too ill to decide, permission was asked of their family or close friends. When no family members were available, a doctor unconnected with the study decided whether the patient should take part.
The five-year TICH-2 trial recruited more than 2,000 patients from 124 hospitals in 12 countries between 2013 and 2017. They were randomly sorted into two patient groups. One received tranexamic acid within eight hours of stroke, and the other was given a saline placebo. In the UK, more than 80 hospitals took part in the study with support from the NIHR clinical research network.
CT scans of the patients’ brains were performed at 24 hours after their stroke, and patients’ progress was monitored and measured at day two and day seven after their stroke. The final follow-up was performed at 90 days.
Tranexamic acid did not improve the outcome for patients after 90 days; there was no significant difference in the number of patients who had subsequently died or had been left with disabilities between the tranexamic acid and placebo groups at three months.
In the tranexamic acid group, however, there were fewer deaths by day seven following the stroke. At day two, fewer people on tranexamic acid experienced a worsening of the bleed on their brain, and they had smaller amounts of blood in the brain, compared with their control group counterparts. Also, the number of patients who had associated serious complications such as pneumonia and brain swelling was lower in the group that had received tranexamic acid treatment, compared with controls.
The trial also found evidence that tranexamic acid might be more effective in patients with lower blood pressure. Participants with blood pressure lower than 170 mm Hg had a more favorable outcome than those with blood pressure of 170 mm Hg and above. Other studies have confirmed that the sooner tranexamic acid is given, the more effective it is. The ideal is to administer the drug within three hours of bleeding onset, according to the researchers. In this study, one-third of patients were given treatment within three hours of stroke onset.
As a result, the researchers have highlighted the need for further studies to find out whether giving an earlier dose of tranexamic acid might be beneficial for patients.
Combination Therapy May Prevent Stroke
Results from an international clinical trial of more than 4,880 participants show that combining clopidogrel and aspirin following a small stroke or experiencing minor stroke symptoms decreases the risk of a new stroke, heart attack, or other ischemic event within 90 days. The combination therapy was also associated with an increase in major bleeding, although many of those episodes were nonfatal and did not occur in the brain. The results were published in the New England Journal of Medicine. The study was supported by the National Institute of Neurological Disorders and Stroke (NINDS), a part of NIH.
“These findings are likely to have a global effect on clinical practice, as these drugs are easily available in many hospitals and clinics,” said Walter Koroshetz, MD, Director of NINDS. “As the benefit of the combination was concentrated in the first two weeks, while risk of bleeding was constant over 90 days, it may be especially valuable in acute management of a minor ischemic stroke or transient ischemic attack (TIA).”
The Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) clinical trial follows an earlier study that showed benefits of this drug combination in a Chinese population. POINT was conducted to see whether the benefits could be expanded to a more diverse group of patients.
The study, led by S. Claiborne Johnston, MD, PhD, Dean and Professor of Neurology at Dell Medical School at the University of Texas at Austin, included patients who had had either a minor stroke or a TIA, in which blood supply to a part of the brain is briefly stopped and can be a risk factor for a larger stroke. Study participants were given clopidogrel and aspirin or aspirin alone to see whether the combination therapy could prevent a larger stroke within three months.
Dr. Johnston’s team found that the combination of clopidogrel and aspirin prevented more ischemic events, such as stroke and heart attack, compared with aspirin alone. The results showed that 5% of patients in the combination therapy group and 6.5% of patients taking only aspirin had such an event within 90 days. The combination therapy was associated with a greater risk of major bleeding or hemorrhage than aspirin alone, however. In the aspirin-only group, 0.4% of patients suffered a major hemorrhage, but 0.9% of patients taking clopidogrel and aspirin had severe bleeding.
The findings suggest that for 1,000 patients, clopidogrel plus aspirin would prevent 15 ischemic attacks, but may cause five instances of major hemorrhage. The majority of these hemorrhages occurred outside of the brain and were not fatal.
“We saw a real benefit with the combination therapy, but that treatment does come with a risk,” said Dr. Johnston. “Overall, the risk of severe bleeding was very small, but it was not zero.”
The study was stopped early because the combination therapy was found to be more effective than aspirin alone in preventing severe strokes, but also due to the risk of severe hemorrhage.
Clopidogrel and aspirin prevent platelets from sticking together and forming clots in blood vessels, although they work in different ways. Aspirin blocks molecules that activate the clotting process, while clopidogrel prevents a specific chemical from attaching to a receptor.
“Each year, strokes cause millions of disabilities around the world, and preventing many of those would lead to not only tremendous health savings, but also to improved quality of life for many individuals and their families,” said Dr. Johnston.
POINT was supported by NINDS’s Neurological Emergencies Treatment Trials (NETT) Network, a system of research institutions dedicated to emergency issues such as stroke.
More research is needed to investigate ways to lower the risk of bleeding and examine the impact of treatment timing on outcomes. In addition, future studies may help identify similar drugs that are associated with fewer adverse events.
Simple Scan Still Effective in Deciding Stroke Treatment
A study led by a neurologist from McGovern Medical School at the University of Texas Health Science Center at Houston (UTHealth) showed that a CT scan could be sufficient for determining thrombectomy treatment in stroke.
Thrombectomy has been shown to be an effective treatment for improving clinical outcomes in stroke up to 24 hours from onset. Stroke is the leading cause of long-term disability and the fourth leading cause of death globally. Imaging must be done to determine the location of the clot and whether the patient is a good candidate for thrombectomy. Physicians use noncontrast simple CT or CT perfusion to see the area.
“The results show that simple imaging, while not perfect, may be good enough. This basic technique is faster, which means patients could potentially be treated more quickly,” said Amrou Sarraj, MD, Associate Professor of Neurology at McGovern Medical School at UTHealth. “The advanced imaging of CT perfusion is not available everywhere, so this could open up the door to identify more people for potential treatment, especially in remote areas.”
Dr. Sarraj was the principal investigator of the study, Optimizing Patient Selection for Endovascular Treatment in Acute Ischemic Stroke (SELECT). The clinical trial enrolled 445 patients who received both simple and advanced imaging at nine academic health centers across the US from January 2016 to February 2018.
The results showed that patients who were treated based on simple imaging had identical clinical outcomes to those treated based on advanced imaging. In addition, those patients who had a good imaging profile (ie, a smaller area of dead brain tissue) had the same clinical outcomes, regardless of which imaging was used.
“If those treated using simple imaging can do as well as those treated by CT perfusion, this is an extremely important breakthrough that warrants further exploration and testing because it could broaden the number of patients having and benefiting from thrombectomy,” said Dr. Sarraj, who is also director of UTHealth’s vascular neurology fellowship program and an attending physician at Memorial Hermann-Texas Medical Center.
The study also revealed that 42% of patients who were excluded from thrombectomy by one of the imaging profiles, but had a good profile on the other type of imaging, had positive clinical outcomes.
“Our results should not be interpreted [to indicate] that advanced perfusion images are not necessary or should not be acquired at all, as they still identified a group of patients that may be treated with thrombectomy when CT alone was not enough. The numbers involved are significant because 17.6% of patients could have been excluded from having surgery if the CT or CT perfusion were relied on alone, so there is a real opportunity here to help more people if both forms of imaging are available,” Dr. Sarraj said.
The study did not randomize patient selection by simple imaging versus advanced imaging. “Although this was the first large cohort study with prespecified imaging criteria, analyses, and objectives to look at imaging type selection, there is room for further refinement to truly test our initial findings and see if they are more affirmative and conclusive,” Dr. Sarraj said.
Thrombolysis May Be Appropriate in Wake-Up Stroke
The randomized controlled WAKE-UP trial, a phase III study of 503 patients with acute stroke of unknown time of symptom onset, assessed whether or not advanced imaging can be used to increase the number of patients eligible for potent clot-busting drugs to include patients waking with a stroke.
The WAKE-UP study showed that in patients with stroke and unknown time of symptom onset and an MRI pattern demonstrating DWI-FLAIR-mismatch, indicating a likely recent time of onset, treatment with alteplase resulted in a better functional outcome at 90 days in an additional 11% of treated patients, compared with placebo, despite an increased risk of intracerebral hemorrhage. The effect size of MRI-guided thrombolysis in stroke with unknown time of symptom onset is comparable to the effect size of thrombolysis administered at less than 4.5 hours. The researchers observed a trend towards an increased risk of early death, however.
The joint lead investigators of WAKE-UP commented on the results. “These data represent a paradigm shift in the treatment of stroke patients with an unknown time of symptom onset,” said Professor Christian Gerloff, MD, Director of Neurology at University Hospital Hamburg-Eppendorf in Germany. “It is the first positive trial of IV thrombolysis relying on patient selection by advanced brain imaging without information on time of symptom onset.”
“MRI-guided IV thrombolysis represents an effective treatment option for stroke patients with unknown [time of] symptom onset, especially for those with minor or moderate stroke who are not eligible for mechanical thrombectomy,” said Götz Thomalla, MD, Executive Senior Physician at University Hospital Hamburg-Eppendorf.
Tranexamic Acid May Benefit Patients With Stroke
Patients with intracerebral hemorrhage may benefit from receiving a drug currently used to treat blood loss from major trauma and bleeding after childbirth, according to an international trial.
The study, led by experts at the University of Nottingham in the United Kingdom and funded by the National Institute for Health Research (NIHR) Health Technology Assessment Program, found that giving tranexamic acid to people who had had intracerebral hemorrhage reduced the number of deaths in the early days following the stroke. It also found that the amount of bleeding in the brain and number of associated serious complications were lower in the patients who had received tranexamic acid treatment.
However, the investigators found no difference in the number of people who were left disabled or had died at three months after their stroke (ie, the study’s primary outcome). The researchers believe that further study is needed on larger groups of patients to enable them to fully understand the potential benefits.
Nikola Sprigg, MD, Professor of Stroke Medicine at the Stroke Trials Unit in the university’s Division of Clinical Neuroscience, led the trial. “Tranexamic acid is cheap, costing less than £15 per patient, and widely available, so it has the potential for reducing death and disability across the world,” she said.
“While we failed to show significant benefits three months after stroke, the reduction in early deaths, amount of bleeding on the brain, and serious complications are signs that this drug may be of benefit in the future. More trials are needed, particularly focusing on giving treatment as soon as possible after the start of bleeding in this emergency condition,” Dr. Sprigg added.
Approximately 15% of all strokes in the UK—affecting around 22,000 people every year—are hemorrhagic and lead to permanent damage. While all people with acute stroke benefit from treatment on a stroke unit, there is currently no specific treatment for hemorrhagic stroke. Many people with hemorrhagic stroke die within a few days. Those who do survive are often left with debilitating disabilities, including paralysis and an inability to speak.
A previous small pilot study by the University of Nottingham and funded by the university and the Stroke Association concluded that a larger study was needed to accurately assess the effectiveness of tranexamic acid. The drug was chosen for the study after previous research showed that it was successful in stopping bleeding in people involved in car accidents.
For the latest trial, people who were diagnosed with bleeding on the brain, confirmed by CT scan, were offered the chance to take part in the study. When the person was too ill to decide, permission was asked of their family or close friends. When no family members were available, a doctor unconnected with the study decided whether the patient should take part.
The five-year TICH-2 trial recruited more than 2,000 patients from 124 hospitals in 12 countries between 2013 and 2017. They were randomly sorted into two patient groups. One received tranexamic acid within eight hours of stroke, and the other was given a saline placebo. In the UK, more than 80 hospitals took part in the study with support from the NIHR clinical research network.
CT scans of the patients’ brains were performed at 24 hours after their stroke, and patients’ progress was monitored and measured at day two and day seven after their stroke. The final follow-up was performed at 90 days.
Tranexamic acid did not improve the outcome for patients after 90 days; there was no significant difference in the number of patients who had subsequently died or had been left with disabilities between the tranexamic acid and placebo groups at three months.
In the tranexamic acid group, however, there were fewer deaths by day seven following the stroke. At day two, fewer people on tranexamic acid experienced a worsening of the bleed on their brain, and they had smaller amounts of blood in the brain, compared with their control group counterparts. Also, the number of patients who had associated serious complications such as pneumonia and brain swelling was lower in the group that had received tranexamic acid treatment, compared with controls.
The trial also found evidence that tranexamic acid might be more effective in patients with lower blood pressure. Participants with blood pressure lower than 170 mm Hg had a more favorable outcome than those with blood pressure of 170 mm Hg and above. Other studies have confirmed that the sooner tranexamic acid is given, the more effective it is. The ideal is to administer the drug within three hours of bleeding onset, according to the researchers. In this study, one-third of patients were given treatment within three hours of stroke onset.
As a result, the researchers have highlighted the need for further studies to find out whether giving an earlier dose of tranexamic acid might be beneficial for patients.
Combination Therapy May Prevent Stroke
Results from an international clinical trial of more than 4,880 participants show that combining clopidogrel and aspirin following a small stroke or experiencing minor stroke symptoms decreases the risk of a new stroke, heart attack, or other ischemic event within 90 days. The combination therapy was also associated with an increase in major bleeding, although many of those episodes were nonfatal and did not occur in the brain. The results were published in the New England Journal of Medicine. The study was supported by the National Institute of Neurological Disorders and Stroke (NINDS), a part of NIH.
“These findings are likely to have a global effect on clinical practice, as these drugs are easily available in many hospitals and clinics,” said Walter Koroshetz, MD, Director of NINDS. “As the benefit of the combination was concentrated in the first two weeks, while risk of bleeding was constant over 90 days, it may be especially valuable in acute management of a minor ischemic stroke or transient ischemic attack (TIA).”
The Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) clinical trial follows an earlier study that showed benefits of this drug combination in a Chinese population. POINT was conducted to see whether the benefits could be expanded to a more diverse group of patients.
The study, led by S. Claiborne Johnston, MD, PhD, Dean and Professor of Neurology at Dell Medical School at the University of Texas at Austin, included patients who had had either a minor stroke or a TIA, in which blood supply to a part of the brain is briefly stopped and can be a risk factor for a larger stroke. Study participants were given clopidogrel and aspirin or aspirin alone to see whether the combination therapy could prevent a larger stroke within three months.
Dr. Johnston’s team found that the combination of clopidogrel and aspirin prevented more ischemic events, such as stroke and heart attack, compared with aspirin alone. The results showed that 5% of patients in the combination therapy group and 6.5% of patients taking only aspirin had such an event within 90 days. The combination therapy was associated with a greater risk of major bleeding or hemorrhage than aspirin alone, however. In the aspirin-only group, 0.4% of patients suffered a major hemorrhage, but 0.9% of patients taking clopidogrel and aspirin had severe bleeding.
The findings suggest that for 1,000 patients, clopidogrel plus aspirin would prevent 15 ischemic attacks, but may cause five instances of major hemorrhage. The majority of these hemorrhages occurred outside of the brain and were not fatal.
“We saw a real benefit with the combination therapy, but that treatment does come with a risk,” said Dr. Johnston. “Overall, the risk of severe bleeding was very small, but it was not zero.”
The study was stopped early because the combination therapy was found to be more effective than aspirin alone in preventing severe strokes, but also due to the risk of severe hemorrhage.
Clopidogrel and aspirin prevent platelets from sticking together and forming clots in blood vessels, although they work in different ways. Aspirin blocks molecules that activate the clotting process, while clopidogrel prevents a specific chemical from attaching to a receptor.
“Each year, strokes cause millions of disabilities around the world, and preventing many of those would lead to not only tremendous health savings, but also to improved quality of life for many individuals and their families,” said Dr. Johnston.
POINT was supported by NINDS’s Neurological Emergencies Treatment Trials (NETT) Network, a system of research institutions dedicated to emergency issues such as stroke.
More research is needed to investigate ways to lower the risk of bleeding and examine the impact of treatment timing on outcomes. In addition, future studies may help identify similar drugs that are associated with fewer adverse events.
Simple Scan Still Effective in Deciding Stroke Treatment
A study led by a neurologist from McGovern Medical School at the University of Texas Health Science Center at Houston (UTHealth) showed that a CT scan could be sufficient for determining thrombectomy treatment in stroke.
Thrombectomy has been shown to be an effective treatment for improving clinical outcomes in stroke up to 24 hours from onset. Stroke is the leading cause of long-term disability and the fourth leading cause of death globally. Imaging must be done to determine the location of the clot and whether the patient is a good candidate for thrombectomy. Physicians use noncontrast simple CT or CT perfusion to see the area.
“The results show that simple imaging, while not perfect, may be good enough. This basic technique is faster, which means patients could potentially be treated more quickly,” said Amrou Sarraj, MD, Associate Professor of Neurology at McGovern Medical School at UTHealth. “The advanced imaging of CT perfusion is not available everywhere, so this could open up the door to identify more people for potential treatment, especially in remote areas.”
Dr. Sarraj was the principal investigator of the study, Optimizing Patient Selection for Endovascular Treatment in Acute Ischemic Stroke (SELECT). The clinical trial enrolled 445 patients who received both simple and advanced imaging at nine academic health centers across the US from January 2016 to February 2018.
The results showed that patients who were treated based on simple imaging had identical clinical outcomes to those treated based on advanced imaging. In addition, those patients who had a good imaging profile (ie, a smaller area of dead brain tissue) had the same clinical outcomes, regardless of which imaging was used.
“If those treated using simple imaging can do as well as those treated by CT perfusion, this is an extremely important breakthrough that warrants further exploration and testing because it could broaden the number of patients having and benefiting from thrombectomy,” said Dr. Sarraj, who is also director of UTHealth’s vascular neurology fellowship program and an attending physician at Memorial Hermann-Texas Medical Center.
The study also revealed that 42% of patients who were excluded from thrombectomy by one of the imaging profiles, but had a good profile on the other type of imaging, had positive clinical outcomes.
“Our results should not be interpreted [to indicate] that advanced perfusion images are not necessary or should not be acquired at all, as they still identified a group of patients that may be treated with thrombectomy when CT alone was not enough. The numbers involved are significant because 17.6% of patients could have been excluded from having surgery if the CT or CT perfusion were relied on alone, so there is a real opportunity here to help more people if both forms of imaging are available,” Dr. Sarraj said.
The study did not randomize patient selection by simple imaging versus advanced imaging. “Although this was the first large cohort study with prespecified imaging criteria, analyses, and objectives to look at imaging type selection, there is room for further refinement to truly test our initial findings and see if they are more affirmative and conclusive,” Dr. Sarraj said.
Thrombolysis May Be Appropriate in Wake-Up Stroke
The randomized controlled WAKE-UP trial, a phase III study of 503 patients with acute stroke of unknown time of symptom onset, assessed whether or not advanced imaging can be used to increase the number of patients eligible for potent clot-busting drugs to include patients waking with a stroke.
The WAKE-UP study showed that in patients with stroke and unknown time of symptom onset and an MRI pattern demonstrating DWI-FLAIR-mismatch, indicating a likely recent time of onset, treatment with alteplase resulted in a better functional outcome at 90 days in an additional 11% of treated patients, compared with placebo, despite an increased risk of intracerebral hemorrhage. The effect size of MRI-guided thrombolysis in stroke with unknown time of symptom onset is comparable to the effect size of thrombolysis administered at less than 4.5 hours. The researchers observed a trend towards an increased risk of early death, however.
The joint lead investigators of WAKE-UP commented on the results. “These data represent a paradigm shift in the treatment of stroke patients with an unknown time of symptom onset,” said Professor Christian Gerloff, MD, Director of Neurology at University Hospital Hamburg-Eppendorf in Germany. “It is the first positive trial of IV thrombolysis relying on patient selection by advanced brain imaging without information on time of symptom onset.”
“MRI-guided IV thrombolysis represents an effective treatment option for stroke patients with unknown [time of] symptom onset, especially for those with minor or moderate stroke who are not eligible for mechanical thrombectomy,” said Götz Thomalla, MD, Executive Senior Physician at University Hospital Hamburg-Eppendorf.
Tranexamic Acid May Benefit Patients With Stroke
Patients with intracerebral hemorrhage may benefit from receiving a drug currently used to treat blood loss from major trauma and bleeding after childbirth, according to an international trial.
The study, led by experts at the University of Nottingham in the United Kingdom and funded by the National Institute for Health Research (NIHR) Health Technology Assessment Program, found that giving tranexamic acid to people who had had intracerebral hemorrhage reduced the number of deaths in the early days following the stroke. It also found that the amount of bleeding in the brain and number of associated serious complications were lower in the patients who had received tranexamic acid treatment.
However, the investigators found no difference in the number of people who were left disabled or had died at three months after their stroke (ie, the study’s primary outcome). The researchers believe that further study is needed on larger groups of patients to enable them to fully understand the potential benefits.
Nikola Sprigg, MD, Professor of Stroke Medicine at the Stroke Trials Unit in the university’s Division of Clinical Neuroscience, led the trial. “Tranexamic acid is cheap, costing less than £15 per patient, and widely available, so it has the potential for reducing death and disability across the world,” she said.
“While we failed to show significant benefits three months after stroke, the reduction in early deaths, amount of bleeding on the brain, and serious complications are signs that this drug may be of benefit in the future. More trials are needed, particularly focusing on giving treatment as soon as possible after the start of bleeding in this emergency condition,” Dr. Sprigg added.
Approximately 15% of all strokes in the UK—affecting around 22,000 people every year—are hemorrhagic and lead to permanent damage. While all people with acute stroke benefit from treatment on a stroke unit, there is currently no specific treatment for hemorrhagic stroke. Many people with hemorrhagic stroke die within a few days. Those who do survive are often left with debilitating disabilities, including paralysis and an inability to speak.
A previous small pilot study by the University of Nottingham and funded by the university and the Stroke Association concluded that a larger study was needed to accurately assess the effectiveness of tranexamic acid. The drug was chosen for the study after previous research showed that it was successful in stopping bleeding in people involved in car accidents.
For the latest trial, people who were diagnosed with bleeding on the brain, confirmed by CT scan, were offered the chance to take part in the study. When the person was too ill to decide, permission was asked of their family or close friends. When no family members were available, a doctor unconnected with the study decided whether the patient should take part.
The five-year TICH-2 trial recruited more than 2,000 patients from 124 hospitals in 12 countries between 2013 and 2017. They were randomly sorted into two patient groups. One received tranexamic acid within eight hours of stroke, and the other was given a saline placebo. In the UK, more than 80 hospitals took part in the study with support from the NIHR clinical research network.
CT scans of the patients’ brains were performed at 24 hours after their stroke, and patients’ progress was monitored and measured at day two and day seven after their stroke. The final follow-up was performed at 90 days.
Tranexamic acid did not improve the outcome for patients after 90 days; there was no significant difference in the number of patients who had subsequently died or had been left with disabilities between the tranexamic acid and placebo groups at three months.
In the tranexamic acid group, however, there were fewer deaths by day seven following the stroke. At day two, fewer people on tranexamic acid experienced a worsening of the bleed on their brain, and they had smaller amounts of blood in the brain, compared with their control group counterparts. Also, the number of patients who had associated serious complications such as pneumonia and brain swelling was lower in the group that had received tranexamic acid treatment, compared with controls.
The trial also found evidence that tranexamic acid might be more effective in patients with lower blood pressure. Participants with blood pressure lower than 170 mm Hg had a more favorable outcome than those with blood pressure of 170 mm Hg and above. Other studies have confirmed that the sooner tranexamic acid is given, the more effective it is. The ideal is to administer the drug within three hours of bleeding onset, according to the researchers. In this study, one-third of patients were given treatment within three hours of stroke onset.
As a result, the researchers have highlighted the need for further studies to find out whether giving an earlier dose of tranexamic acid might be beneficial for patients.
Combination Therapy May Prevent Stroke
Results from an international clinical trial of more than 4,880 participants show that combining clopidogrel and aspirin following a small stroke or experiencing minor stroke symptoms decreases the risk of a new stroke, heart attack, or other ischemic event within 90 days. The combination therapy was also associated with an increase in major bleeding, although many of those episodes were nonfatal and did not occur in the brain. The results were published in the New England Journal of Medicine. The study was supported by the National Institute of Neurological Disorders and Stroke (NINDS), a part of NIH.
“These findings are likely to have a global effect on clinical practice, as these drugs are easily available in many hospitals and clinics,” said Walter Koroshetz, MD, Director of NINDS. “As the benefit of the combination was concentrated in the first two weeks, while risk of bleeding was constant over 90 days, it may be especially valuable in acute management of a minor ischemic stroke or transient ischemic attack (TIA).”
The Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) clinical trial follows an earlier study that showed benefits of this drug combination in a Chinese population. POINT was conducted to see whether the benefits could be expanded to a more diverse group of patients.
The study, led by S. Claiborne Johnston, MD, PhD, Dean and Professor of Neurology at Dell Medical School at the University of Texas at Austin, included patients who had had either a minor stroke or a TIA, in which blood supply to a part of the brain is briefly stopped and can be a risk factor for a larger stroke. Study participants were given clopidogrel and aspirin or aspirin alone to see whether the combination therapy could prevent a larger stroke within three months.
Dr. Johnston’s team found that the combination of clopidogrel and aspirin prevented more ischemic events, such as stroke and heart attack, compared with aspirin alone. The results showed that 5% of patients in the combination therapy group and 6.5% of patients taking only aspirin had such an event within 90 days. The combination therapy was associated with a greater risk of major bleeding or hemorrhage than aspirin alone, however. In the aspirin-only group, 0.4% of patients suffered a major hemorrhage, but 0.9% of patients taking clopidogrel and aspirin had severe bleeding.
The findings suggest that for 1,000 patients, clopidogrel plus aspirin would prevent 15 ischemic attacks, but may cause five instances of major hemorrhage. The majority of these hemorrhages occurred outside of the brain and were not fatal.
“We saw a real benefit with the combination therapy, but that treatment does come with a risk,” said Dr. Johnston. “Overall, the risk of severe bleeding was very small, but it was not zero.”
The study was stopped early because the combination therapy was found to be more effective than aspirin alone in preventing severe strokes, but also due to the risk of severe hemorrhage.
Clopidogrel and aspirin prevent platelets from sticking together and forming clots in blood vessels, although they work in different ways. Aspirin blocks molecules that activate the clotting process, while clopidogrel prevents a specific chemical from attaching to a receptor.
“Each year, strokes cause millions of disabilities around the world, and preventing many of those would lead to not only tremendous health savings, but also to improved quality of life for many individuals and their families,” said Dr. Johnston.
POINT was supported by NINDS’s Neurological Emergencies Treatment Trials (NETT) Network, a system of research institutions dedicated to emergency issues such as stroke.
More research is needed to investigate ways to lower the risk of bleeding and examine the impact of treatment timing on outcomes. In addition, future studies may help identify similar drugs that are associated with fewer adverse events.
Simple Scan Still Effective in Deciding Stroke Treatment
A study led by a neurologist from McGovern Medical School at the University of Texas Health Science Center at Houston (UTHealth) showed that a CT scan could be sufficient for determining thrombectomy treatment in stroke.
Thrombectomy has been shown to be an effective treatment for improving clinical outcomes in stroke up to 24 hours from onset. Stroke is the leading cause of long-term disability and the fourth leading cause of death globally. Imaging must be done to determine the location of the clot and whether the patient is a good candidate for thrombectomy. Physicians use noncontrast simple CT or CT perfusion to see the area.
“The results show that simple imaging, while not perfect, may be good enough. This basic technique is faster, which means patients could potentially be treated more quickly,” said Amrou Sarraj, MD, Associate Professor of Neurology at McGovern Medical School at UTHealth. “The advanced imaging of CT perfusion is not available everywhere, so this could open up the door to identify more people for potential treatment, especially in remote areas.”
Dr. Sarraj was the principal investigator of the study, Optimizing Patient Selection for Endovascular Treatment in Acute Ischemic Stroke (SELECT). The clinical trial enrolled 445 patients who received both simple and advanced imaging at nine academic health centers across the US from January 2016 to February 2018.
The results showed that patients who were treated based on simple imaging had identical clinical outcomes to those treated based on advanced imaging. In addition, those patients who had a good imaging profile (ie, a smaller area of dead brain tissue) had the same clinical outcomes, regardless of which imaging was used.
“If those treated using simple imaging can do as well as those treated by CT perfusion, this is an extremely important breakthrough that warrants further exploration and testing because it could broaden the number of patients having and benefiting from thrombectomy,” said Dr. Sarraj, who is also director of UTHealth’s vascular neurology fellowship program and an attending physician at Memorial Hermann-Texas Medical Center.
The study also revealed that 42% of patients who were excluded from thrombectomy by one of the imaging profiles, but had a good profile on the other type of imaging, had positive clinical outcomes.
“Our results should not be interpreted [to indicate] that advanced perfusion images are not necessary or should not be acquired at all, as they still identified a group of patients that may be treated with thrombectomy when CT alone was not enough. The numbers involved are significant because 17.6% of patients could have been excluded from having surgery if the CT or CT perfusion were relied on alone, so there is a real opportunity here to help more people if both forms of imaging are available,” Dr. Sarraj said.
The study did not randomize patient selection by simple imaging versus advanced imaging. “Although this was the first large cohort study with prespecified imaging criteria, analyses, and objectives to look at imaging type selection, there is room for further refinement to truly test our initial findings and see if they are more affirmative and conclusive,” Dr. Sarraj said.
Thrombolysis May Be Appropriate in Wake-Up Stroke
The randomized controlled WAKE-UP trial, a phase III study of 503 patients with acute stroke of unknown time of symptom onset, assessed whether or not advanced imaging can be used to increase the number of patients eligible for potent clot-busting drugs to include patients waking with a stroke.
The WAKE-UP study showed that in patients with stroke and unknown time of symptom onset and an MRI pattern demonstrating DWI-FLAIR-mismatch, indicating a likely recent time of onset, treatment with alteplase resulted in a better functional outcome at 90 days in an additional 11% of treated patients, compared with placebo, despite an increased risk of intracerebral hemorrhage. The effect size of MRI-guided thrombolysis in stroke with unknown time of symptom onset is comparable to the effect size of thrombolysis administered at less than 4.5 hours. The researchers observed a trend towards an increased risk of early death, however.
The joint lead investigators of WAKE-UP commented on the results. “These data represent a paradigm shift in the treatment of stroke patients with an unknown time of symptom onset,” said Professor Christian Gerloff, MD, Director of Neurology at University Hospital Hamburg-Eppendorf in Germany. “It is the first positive trial of IV thrombolysis relying on patient selection by advanced brain imaging without information on time of symptom onset.”
“MRI-guided IV thrombolysis represents an effective treatment option for stroke patients with unknown [time of] symptom onset, especially for those with minor or moderate stroke who are not eligible for mechanical thrombectomy,” said Götz Thomalla, MD, Executive Senior Physician at University Hospital Hamburg-Eppendorf.
