User login
‘Striking’ differences in BP when wrong cuff size is used
Strong new evidence on the need to use an appropriately sized cuff in blood pressure measurement has come from the cross-sectional randomized trial Cuff(SZ).
The study found that in people in whom a small adult cuff was appropriate, systolic BP readings were on average 3.6 mm Hg lower when a regular adult size cuff was used.
However, systolic readings were on average 4.8 mm Hg higher when a regular cuff was used in people who required a large adult cuff and 19.5 mm Hg higher in those needing an extra-large cuff based on their mid-arm circumference.
The diastolic readings followed a similar pattern (-1.3 mm Hg, 1.8 mm Hg, and 7.4 mm Hg, respectively).
“We found that using the regular adult cuff in all individuals had striking differences in blood pressure,” lead author Tammy M. Brady, MD, PhD, Johns Hopkins University School of Medicine, Baltimore, told this news organization. “And that has a lot of clinical implications.”
She noted, for example, that people who required an extra-large cuff and were measured with a regular cuff had an average BP of 144/86.7 mm Hg, which is in the stage 2 hypertension range. But when the correct size cuff was used, the average BP was 124.5/79.3 mm Hg, or in the prehypertensive range.
Overall, the overestimation of BP due to using too small a cuff misclassified 39% of people as being hypertensive, while the underestimation of BP due to using a cuff that was too large missed 22% of people with hypertension.
“So, I think clinicians really need to have a renewed emphasis on cuff size, especially in populations where obesity is highly prevalent and many of their patients require extra-large cuffs, because those are the populations that are most impacted by mis-cuffing,” Dr. Brady said.
The findings were presented in an E-poster at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health (EPI/Lifestyle) 2022 conference sponsored by the American Heart Association.
Willie Lawrence, MD, chair of the AHA’s National Hypertension Control Initiative Advisory Committee, said in an interview that the magnitude of inaccuracy observed by the researchers “makes this a very, very important study.”
“Is it the first of its kind, no, but it’s incredibly important because it was so well done, and it comes at a time when people are once again dealing with issues around equity, and this study can have a significant impact on the state of hypertension in diverse communities,” said Dr. Lawrence, a cardiologist with Spectrum Health Lakeland, Benton Harbor, Michigan.
Previous studies examining the issue were older, had few participants, and used mercury sphygmomanometers instead of automated devices, which are typically recommended by professional societies for screening hypertension in adults, Dr. Brady explained.
For the Cuff Size Blood Pressure Measurement trial, 195 adults recruited from the community underwent 2 to 3 sets of 3 BP readings, 30 seconds apart, with an automated and validated device (Welch Allyn ProB 2000) using a BP cuff that was appropriated sized, one size lower, and one size higher. The order of cuff sizes was randomized. Before each set, patients walked for 2 minutes, followed by 5 minutes of rest to eliminate the potential effect of longer resting periods between tests on the results. The room was also kept quiet and participants were asked not to speak or use a smart phone.
Participants had a mean age of 54 years, 34% were male, 68% were Black, and 36% had a body mass index of at least 30 kg/m2, meeting the criteria for obesity.
Roughly one-half had a self-reported hypertension diagnosis, 31% had a systolic BP of 130 mm Hg or greater, and 26% had a diastolic BP of 80 mm Hg or greater.
Based on arm circumference (mean, 34 cm), the appropriate adult cuff size was small (20-25 cm) in 18%, regular (25.1-32 cm) in 28%, large (32.1-40 cm) in 34%, and extra-large (40.1-55 cm) in 21%.
Dr. Brady pointed out that the most recent hypertension guidelines detail sources of inaccuracy in BP measurement and say that if too small a cuff size is used, the blood pressure could be different by 2 to 11 mm Hg. “And what we show, is it can be anywhere from 5 to 20 mm Hg. So, I think that’s a significant difference from what studies have shown so far and is going to be very surprising to clinicians.”
A 2019 AHA scientific statement on the measurement of blood pressure stresses the importance of cuff size, and last year, the American Medical Association launched a new initiative to standardize training in BP measurement for future physicians and health care professionals.
Previous work also showed that children as young as 3 to 5 years of age often require an adult cuff size, and those in the 12- to 15-year age group may need an extra-large cuff, or what is often referred to as a thigh cuff, said Dr. Brady, who is also the medical director of the pediatric hypertension program at Johns Hopkins Children’s Center.
“Part of the problem is that many physicians aren’t often the one doing the measurement and that others may not be as in tune with some of these data and initiatives,” she said.
Other barriers are cost and availability. Offices and clinics don’t routinely stock multiple cuff sizes in exam rooms, and devices sold over the counter typically come with a regular adult cuff, Dr. Brady said. An extra cuff could add $25 to $50 on top of the $25 to $50 for the device for the growing number of patients measuring BP remotely.
“During the pandemic, I was trying to do telemedicine with my hypertensive patients, but the children who had significant obesity couldn’t afford or find blood pressure devices that had a cuff that was big enough for them,” she said. “It just wasn’t something that they could get. So I think people just don’t recognize how important this is.”
A version of this article first appeared on Medscape.com.
Strong new evidence on the need to use an appropriately sized cuff in blood pressure measurement has come from the cross-sectional randomized trial Cuff(SZ).
The study found that in people in whom a small adult cuff was appropriate, systolic BP readings were on average 3.6 mm Hg lower when a regular adult size cuff was used.
However, systolic readings were on average 4.8 mm Hg higher when a regular cuff was used in people who required a large adult cuff and 19.5 mm Hg higher in those needing an extra-large cuff based on their mid-arm circumference.
The diastolic readings followed a similar pattern (-1.3 mm Hg, 1.8 mm Hg, and 7.4 mm Hg, respectively).
“We found that using the regular adult cuff in all individuals had striking differences in blood pressure,” lead author Tammy M. Brady, MD, PhD, Johns Hopkins University School of Medicine, Baltimore, told this news organization. “And that has a lot of clinical implications.”
She noted, for example, that people who required an extra-large cuff and were measured with a regular cuff had an average BP of 144/86.7 mm Hg, which is in the stage 2 hypertension range. But when the correct size cuff was used, the average BP was 124.5/79.3 mm Hg, or in the prehypertensive range.
Overall, the overestimation of BP due to using too small a cuff misclassified 39% of people as being hypertensive, while the underestimation of BP due to using a cuff that was too large missed 22% of people with hypertension.
“So, I think clinicians really need to have a renewed emphasis on cuff size, especially in populations where obesity is highly prevalent and many of their patients require extra-large cuffs, because those are the populations that are most impacted by mis-cuffing,” Dr. Brady said.
The findings were presented in an E-poster at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health (EPI/Lifestyle) 2022 conference sponsored by the American Heart Association.
Willie Lawrence, MD, chair of the AHA’s National Hypertension Control Initiative Advisory Committee, said in an interview that the magnitude of inaccuracy observed by the researchers “makes this a very, very important study.”
“Is it the first of its kind, no, but it’s incredibly important because it was so well done, and it comes at a time when people are once again dealing with issues around equity, and this study can have a significant impact on the state of hypertension in diverse communities,” said Dr. Lawrence, a cardiologist with Spectrum Health Lakeland, Benton Harbor, Michigan.
Previous studies examining the issue were older, had few participants, and used mercury sphygmomanometers instead of automated devices, which are typically recommended by professional societies for screening hypertension in adults, Dr. Brady explained.
For the Cuff Size Blood Pressure Measurement trial, 195 adults recruited from the community underwent 2 to 3 sets of 3 BP readings, 30 seconds apart, with an automated and validated device (Welch Allyn ProB 2000) using a BP cuff that was appropriated sized, one size lower, and one size higher. The order of cuff sizes was randomized. Before each set, patients walked for 2 minutes, followed by 5 minutes of rest to eliminate the potential effect of longer resting periods between tests on the results. The room was also kept quiet and participants were asked not to speak or use a smart phone.
Participants had a mean age of 54 years, 34% were male, 68% were Black, and 36% had a body mass index of at least 30 kg/m2, meeting the criteria for obesity.
Roughly one-half had a self-reported hypertension diagnosis, 31% had a systolic BP of 130 mm Hg or greater, and 26% had a diastolic BP of 80 mm Hg or greater.
Based on arm circumference (mean, 34 cm), the appropriate adult cuff size was small (20-25 cm) in 18%, regular (25.1-32 cm) in 28%, large (32.1-40 cm) in 34%, and extra-large (40.1-55 cm) in 21%.
Dr. Brady pointed out that the most recent hypertension guidelines detail sources of inaccuracy in BP measurement and say that if too small a cuff size is used, the blood pressure could be different by 2 to 11 mm Hg. “And what we show, is it can be anywhere from 5 to 20 mm Hg. So, I think that’s a significant difference from what studies have shown so far and is going to be very surprising to clinicians.”
A 2019 AHA scientific statement on the measurement of blood pressure stresses the importance of cuff size, and last year, the American Medical Association launched a new initiative to standardize training in BP measurement for future physicians and health care professionals.
Previous work also showed that children as young as 3 to 5 years of age often require an adult cuff size, and those in the 12- to 15-year age group may need an extra-large cuff, or what is often referred to as a thigh cuff, said Dr. Brady, who is also the medical director of the pediatric hypertension program at Johns Hopkins Children’s Center.
“Part of the problem is that many physicians aren’t often the one doing the measurement and that others may not be as in tune with some of these data and initiatives,” she said.
Other barriers are cost and availability. Offices and clinics don’t routinely stock multiple cuff sizes in exam rooms, and devices sold over the counter typically come with a regular adult cuff, Dr. Brady said. An extra cuff could add $25 to $50 on top of the $25 to $50 for the device for the growing number of patients measuring BP remotely.
“During the pandemic, I was trying to do telemedicine with my hypertensive patients, but the children who had significant obesity couldn’t afford or find blood pressure devices that had a cuff that was big enough for them,” she said. “It just wasn’t something that they could get. So I think people just don’t recognize how important this is.”
A version of this article first appeared on Medscape.com.
Strong new evidence on the need to use an appropriately sized cuff in blood pressure measurement has come from the cross-sectional randomized trial Cuff(SZ).
The study found that in people in whom a small adult cuff was appropriate, systolic BP readings were on average 3.6 mm Hg lower when a regular adult size cuff was used.
However, systolic readings were on average 4.8 mm Hg higher when a regular cuff was used in people who required a large adult cuff and 19.5 mm Hg higher in those needing an extra-large cuff based on their mid-arm circumference.
The diastolic readings followed a similar pattern (-1.3 mm Hg, 1.8 mm Hg, and 7.4 mm Hg, respectively).
“We found that using the regular adult cuff in all individuals had striking differences in blood pressure,” lead author Tammy M. Brady, MD, PhD, Johns Hopkins University School of Medicine, Baltimore, told this news organization. “And that has a lot of clinical implications.”
She noted, for example, that people who required an extra-large cuff and were measured with a regular cuff had an average BP of 144/86.7 mm Hg, which is in the stage 2 hypertension range. But when the correct size cuff was used, the average BP was 124.5/79.3 mm Hg, or in the prehypertensive range.
Overall, the overestimation of BP due to using too small a cuff misclassified 39% of people as being hypertensive, while the underestimation of BP due to using a cuff that was too large missed 22% of people with hypertension.
“So, I think clinicians really need to have a renewed emphasis on cuff size, especially in populations where obesity is highly prevalent and many of their patients require extra-large cuffs, because those are the populations that are most impacted by mis-cuffing,” Dr. Brady said.
The findings were presented in an E-poster at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health (EPI/Lifestyle) 2022 conference sponsored by the American Heart Association.
Willie Lawrence, MD, chair of the AHA’s National Hypertension Control Initiative Advisory Committee, said in an interview that the magnitude of inaccuracy observed by the researchers “makes this a very, very important study.”
“Is it the first of its kind, no, but it’s incredibly important because it was so well done, and it comes at a time when people are once again dealing with issues around equity, and this study can have a significant impact on the state of hypertension in diverse communities,” said Dr. Lawrence, a cardiologist with Spectrum Health Lakeland, Benton Harbor, Michigan.
Previous studies examining the issue were older, had few participants, and used mercury sphygmomanometers instead of automated devices, which are typically recommended by professional societies for screening hypertension in adults, Dr. Brady explained.
For the Cuff Size Blood Pressure Measurement trial, 195 adults recruited from the community underwent 2 to 3 sets of 3 BP readings, 30 seconds apart, with an automated and validated device (Welch Allyn ProB 2000) using a BP cuff that was appropriated sized, one size lower, and one size higher. The order of cuff sizes was randomized. Before each set, patients walked for 2 minutes, followed by 5 minutes of rest to eliminate the potential effect of longer resting periods between tests on the results. The room was also kept quiet and participants were asked not to speak or use a smart phone.
Participants had a mean age of 54 years, 34% were male, 68% were Black, and 36% had a body mass index of at least 30 kg/m2, meeting the criteria for obesity.
Roughly one-half had a self-reported hypertension diagnosis, 31% had a systolic BP of 130 mm Hg or greater, and 26% had a diastolic BP of 80 mm Hg or greater.
Based on arm circumference (mean, 34 cm), the appropriate adult cuff size was small (20-25 cm) in 18%, regular (25.1-32 cm) in 28%, large (32.1-40 cm) in 34%, and extra-large (40.1-55 cm) in 21%.
Dr. Brady pointed out that the most recent hypertension guidelines detail sources of inaccuracy in BP measurement and say that if too small a cuff size is used, the blood pressure could be different by 2 to 11 mm Hg. “And what we show, is it can be anywhere from 5 to 20 mm Hg. So, I think that’s a significant difference from what studies have shown so far and is going to be very surprising to clinicians.”
A 2019 AHA scientific statement on the measurement of blood pressure stresses the importance of cuff size, and last year, the American Medical Association launched a new initiative to standardize training in BP measurement for future physicians and health care professionals.
Previous work also showed that children as young as 3 to 5 years of age often require an adult cuff size, and those in the 12- to 15-year age group may need an extra-large cuff, or what is often referred to as a thigh cuff, said Dr. Brady, who is also the medical director of the pediatric hypertension program at Johns Hopkins Children’s Center.
“Part of the problem is that many physicians aren’t often the one doing the measurement and that others may not be as in tune with some of these data and initiatives,” she said.
Other barriers are cost and availability. Offices and clinics don’t routinely stock multiple cuff sizes in exam rooms, and devices sold over the counter typically come with a regular adult cuff, Dr. Brady said. An extra cuff could add $25 to $50 on top of the $25 to $50 for the device for the growing number of patients measuring BP remotely.
“During the pandemic, I was trying to do telemedicine with my hypertensive patients, but the children who had significant obesity couldn’t afford or find blood pressure devices that had a cuff that was big enough for them,” she said. “It just wasn’t something that they could get. So I think people just don’t recognize how important this is.”
A version of this article first appeared on Medscape.com.
Robotic transcranial Doppler improves PFO detection after stroke
in a new study.
Being far easier to perform than regular transcranial Doppler ultrasound, it’s hoped that use of the robotic device will enable many more patients to undergo the more sensitive transcranial screening modality and increase the number of shunts identified.
“I believe robot-assisted transcranial Doppler ultrasound can fill the gap between the gold standard transcranial Doppler and transthoracic echocardiography, which is the current standard of care,” said lead author Mark Rubin, MD.
Dr. Rubin, who is assistant professor of neurology at University of Tennessee Health Science Center, Memphis, presented results of the BUBL study at the International Stroke Conference (ISC) 2022, where they were greeted with applause from the floor.
An improvement in the current standard of care
Dr. Rubin explained that patients with suspected embolic stroke are routinely screened for shunts in the heart, such as patent foramen ovale (PFO), that allow blood to flow from the right chamber to the left chamber and can lead to clots from the venous system, accessing the arterial system, then traveling to the brain and causing a stroke.
The current standard of care in screening for such shunts is the use of transthoracic echocardiography (TTE), a widely available and easy to perform, non-invasive procedure. “But we have known for decades that TTE does not pick up these shunts very well. With a sensitivity of only around 45%, it identifies less than half of the patients affected,” Dr. Rubin noted.
The more sensitive transesophageal echocardiography (TEE) gives much better results, but it is an invasive and unpleasant procedure with the ultrasound probe being passed down the throat, and the patient needing to be sedated, so it’s not appropriate for everyone, he noted.
“Transcranial Doppler ultrasound (TCD) also gives excellent results, with a sensitivity of about 96% for detecting PFO, but this procedure is difficult to perform and requires a great deal of skill in placing the probes in the right position and interpreting the signal,” Dr. Rubin said. “TCD has been around for decades, but it hasn’t caught on, as it is too difficult to do. It takes a lot of time to learn the technique.”
“With the robotic-assisted transcranial Doppler device, we can achieve the sensitivity of TCD without needing expert operators. This should vastly improve accessibility to this technology,” he said. “With such technology we can make significant strides into more accurate diagnoses on the cause of stroke, which should lead to better preventive treatments in those found to have right-to-left shunts.”
Robotic detection of shunts
For the BUBL study, the robotic TCD technique was compared with the standard TTE in 129 patients who had a diagnosis of presumed embolic stroke or transient ischemic attack (TIA), with all patients undergoing both procedures.
The robotic TCD device resembles a giant pair of headphones containing the ultrasound probes, which are attached to a frame. In the study, it was operated by a health care professional without TCD skills. Each ultrasound probe independently scans the temporal area autonomously – with angling and positive pressure against the scalp akin to a sonographer – to find and optimize bilateral middle cerebral artery signals, Dr. Rubin explained.
The primary endpoint was the detection of a right-to-left shunt. This occurred in 82 of the 129 patients (63.6%) with the robotic TCD device but in only 27 patients (20.9%) when TTE was used. This gives an absolute difference of 42.6% (95% confidence interval, 28.6%-56.7%; P < .001), which Dr. Rubin described as “astounding.”
However, he said he was not surprised by these results.
“In my experience with transcranial Doppler, I find shunts in patients every day that have not been seen with transthoracic echo,” he commented.
He noted that a previous meta-analysis has suggested a similar difference between TCD and transthoracic echo, but the current study provides prospectively collected data produced in a clinical trial setting and is therefore more reliable.
“What I hope comes from this is that more patients will be able to undergo transcranial Doppler, which is a far superior screening technique for identifying right-to-left shunts. There is so much evidence to support the use of transcranial Doppler, but with this new artificial-intelligence robotic device, we don’t need an expert to use it,” Dr. Rubin said.
He explained that finding a right-to-left shunt in stroke patients is particularly important, as it can direct treatment strategies to reduce future risk of recurrent strokes.
“If a patient has a large shunt, then they have a high risk of having another stroke, and the PFO should be closed.”
In this study, the robotic-assisted TCD detected three times as many large shunts that were considered “intervenable,” compared with transthoracic echo, identifying these shunts in 35 patients (27%) compared to just 13 (10%) with TTE.
“Of the 35 patients with intervenable shunts detected with robotic transcranial Doppler, TTE was completely negative in 18 of them and only suggested a small shunt in the others. So, the standard of care (TTE) missed half the patients with intervenable PFOs,” Dr. Rubin reported.
Study should ‘dramatically change’ practice
Commenting on the study, Patrick Lyden, MD, professor of physiology and neuroscience and of neurology, University of Southern California, Los Angeles, said: “Most clinicians hesitate to use transcranial Doppler given the need for specialized technical expertise to obtain a reliable result. This study showed that a robotic transcranial Doppler device – which can be applied by any cardiac non-invasive lab technician – provides reliable and rigorous data.”
He added: “This result will dramatically change the typical evaluation of patients with suspected PFO: In place of an invasive transesophageal echo that requires anesthesia and a cardiologist, most patients can have a non-invasive, robotic-guided transcranial Doppler and get the same diagnostic benefit.”
Dr. Lyden also pointed out that the cost of TCD is typically one-tenth that of TEE, although he said the cost of the robotic guided TCD “is not clear.”
A representative of the company that makes the robotic assisted device, NovaSignal, says the cost of the equipment is approximately $250,000, but “understanding the importance of the technology, we work with each hospital to meet their unique needs.”
The company adds that it currently has “over 45 commercial solutions deployed across 25 centers with 3-4 times growth expected year over year.”
The study was supported by NovaSignal, the company which makes the robotic device. Dr. Rubin reports acting as a consultant for the NovaSignal.
A version of this article first appeared on Medscape.com.
in a new study.
Being far easier to perform than regular transcranial Doppler ultrasound, it’s hoped that use of the robotic device will enable many more patients to undergo the more sensitive transcranial screening modality and increase the number of shunts identified.
“I believe robot-assisted transcranial Doppler ultrasound can fill the gap between the gold standard transcranial Doppler and transthoracic echocardiography, which is the current standard of care,” said lead author Mark Rubin, MD.
Dr. Rubin, who is assistant professor of neurology at University of Tennessee Health Science Center, Memphis, presented results of the BUBL study at the International Stroke Conference (ISC) 2022, where they were greeted with applause from the floor.
An improvement in the current standard of care
Dr. Rubin explained that patients with suspected embolic stroke are routinely screened for shunts in the heart, such as patent foramen ovale (PFO), that allow blood to flow from the right chamber to the left chamber and can lead to clots from the venous system, accessing the arterial system, then traveling to the brain and causing a stroke.
The current standard of care in screening for such shunts is the use of transthoracic echocardiography (TTE), a widely available and easy to perform, non-invasive procedure. “But we have known for decades that TTE does not pick up these shunts very well. With a sensitivity of only around 45%, it identifies less than half of the patients affected,” Dr. Rubin noted.
The more sensitive transesophageal echocardiography (TEE) gives much better results, but it is an invasive and unpleasant procedure with the ultrasound probe being passed down the throat, and the patient needing to be sedated, so it’s not appropriate for everyone, he noted.
“Transcranial Doppler ultrasound (TCD) also gives excellent results, with a sensitivity of about 96% for detecting PFO, but this procedure is difficult to perform and requires a great deal of skill in placing the probes in the right position and interpreting the signal,” Dr. Rubin said. “TCD has been around for decades, but it hasn’t caught on, as it is too difficult to do. It takes a lot of time to learn the technique.”
“With the robotic-assisted transcranial Doppler device, we can achieve the sensitivity of TCD without needing expert operators. This should vastly improve accessibility to this technology,” he said. “With such technology we can make significant strides into more accurate diagnoses on the cause of stroke, which should lead to better preventive treatments in those found to have right-to-left shunts.”
Robotic detection of shunts
For the BUBL study, the robotic TCD technique was compared with the standard TTE in 129 patients who had a diagnosis of presumed embolic stroke or transient ischemic attack (TIA), with all patients undergoing both procedures.
The robotic TCD device resembles a giant pair of headphones containing the ultrasound probes, which are attached to a frame. In the study, it was operated by a health care professional without TCD skills. Each ultrasound probe independently scans the temporal area autonomously – with angling and positive pressure against the scalp akin to a sonographer – to find and optimize bilateral middle cerebral artery signals, Dr. Rubin explained.
The primary endpoint was the detection of a right-to-left shunt. This occurred in 82 of the 129 patients (63.6%) with the robotic TCD device but in only 27 patients (20.9%) when TTE was used. This gives an absolute difference of 42.6% (95% confidence interval, 28.6%-56.7%; P < .001), which Dr. Rubin described as “astounding.”
However, he said he was not surprised by these results.
“In my experience with transcranial Doppler, I find shunts in patients every day that have not been seen with transthoracic echo,” he commented.
He noted that a previous meta-analysis has suggested a similar difference between TCD and transthoracic echo, but the current study provides prospectively collected data produced in a clinical trial setting and is therefore more reliable.
“What I hope comes from this is that more patients will be able to undergo transcranial Doppler, which is a far superior screening technique for identifying right-to-left shunts. There is so much evidence to support the use of transcranial Doppler, but with this new artificial-intelligence robotic device, we don’t need an expert to use it,” Dr. Rubin said.
He explained that finding a right-to-left shunt in stroke patients is particularly important, as it can direct treatment strategies to reduce future risk of recurrent strokes.
“If a patient has a large shunt, then they have a high risk of having another stroke, and the PFO should be closed.”
In this study, the robotic-assisted TCD detected three times as many large shunts that were considered “intervenable,” compared with transthoracic echo, identifying these shunts in 35 patients (27%) compared to just 13 (10%) with TTE.
“Of the 35 patients with intervenable shunts detected with robotic transcranial Doppler, TTE was completely negative in 18 of them and only suggested a small shunt in the others. So, the standard of care (TTE) missed half the patients with intervenable PFOs,” Dr. Rubin reported.
Study should ‘dramatically change’ practice
Commenting on the study, Patrick Lyden, MD, professor of physiology and neuroscience and of neurology, University of Southern California, Los Angeles, said: “Most clinicians hesitate to use transcranial Doppler given the need for specialized technical expertise to obtain a reliable result. This study showed that a robotic transcranial Doppler device – which can be applied by any cardiac non-invasive lab technician – provides reliable and rigorous data.”
He added: “This result will dramatically change the typical evaluation of patients with suspected PFO: In place of an invasive transesophageal echo that requires anesthesia and a cardiologist, most patients can have a non-invasive, robotic-guided transcranial Doppler and get the same diagnostic benefit.”
Dr. Lyden also pointed out that the cost of TCD is typically one-tenth that of TEE, although he said the cost of the robotic guided TCD “is not clear.”
A representative of the company that makes the robotic assisted device, NovaSignal, says the cost of the equipment is approximately $250,000, but “understanding the importance of the technology, we work with each hospital to meet their unique needs.”
The company adds that it currently has “over 45 commercial solutions deployed across 25 centers with 3-4 times growth expected year over year.”
The study was supported by NovaSignal, the company which makes the robotic device. Dr. Rubin reports acting as a consultant for the NovaSignal.
A version of this article first appeared on Medscape.com.
in a new study.
Being far easier to perform than regular transcranial Doppler ultrasound, it’s hoped that use of the robotic device will enable many more patients to undergo the more sensitive transcranial screening modality and increase the number of shunts identified.
“I believe robot-assisted transcranial Doppler ultrasound can fill the gap between the gold standard transcranial Doppler and transthoracic echocardiography, which is the current standard of care,” said lead author Mark Rubin, MD.
Dr. Rubin, who is assistant professor of neurology at University of Tennessee Health Science Center, Memphis, presented results of the BUBL study at the International Stroke Conference (ISC) 2022, where they were greeted with applause from the floor.
An improvement in the current standard of care
Dr. Rubin explained that patients with suspected embolic stroke are routinely screened for shunts in the heart, such as patent foramen ovale (PFO), that allow blood to flow from the right chamber to the left chamber and can lead to clots from the venous system, accessing the arterial system, then traveling to the brain and causing a stroke.
The current standard of care in screening for such shunts is the use of transthoracic echocardiography (TTE), a widely available and easy to perform, non-invasive procedure. “But we have known for decades that TTE does not pick up these shunts very well. With a sensitivity of only around 45%, it identifies less than half of the patients affected,” Dr. Rubin noted.
The more sensitive transesophageal echocardiography (TEE) gives much better results, but it is an invasive and unpleasant procedure with the ultrasound probe being passed down the throat, and the patient needing to be sedated, so it’s not appropriate for everyone, he noted.
“Transcranial Doppler ultrasound (TCD) also gives excellent results, with a sensitivity of about 96% for detecting PFO, but this procedure is difficult to perform and requires a great deal of skill in placing the probes in the right position and interpreting the signal,” Dr. Rubin said. “TCD has been around for decades, but it hasn’t caught on, as it is too difficult to do. It takes a lot of time to learn the technique.”
“With the robotic-assisted transcranial Doppler device, we can achieve the sensitivity of TCD without needing expert operators. This should vastly improve accessibility to this technology,” he said. “With such technology we can make significant strides into more accurate diagnoses on the cause of stroke, which should lead to better preventive treatments in those found to have right-to-left shunts.”
Robotic detection of shunts
For the BUBL study, the robotic TCD technique was compared with the standard TTE in 129 patients who had a diagnosis of presumed embolic stroke or transient ischemic attack (TIA), with all patients undergoing both procedures.
The robotic TCD device resembles a giant pair of headphones containing the ultrasound probes, which are attached to a frame. In the study, it was operated by a health care professional without TCD skills. Each ultrasound probe independently scans the temporal area autonomously – with angling and positive pressure against the scalp akin to a sonographer – to find and optimize bilateral middle cerebral artery signals, Dr. Rubin explained.
The primary endpoint was the detection of a right-to-left shunt. This occurred in 82 of the 129 patients (63.6%) with the robotic TCD device but in only 27 patients (20.9%) when TTE was used. This gives an absolute difference of 42.6% (95% confidence interval, 28.6%-56.7%; P < .001), which Dr. Rubin described as “astounding.”
However, he said he was not surprised by these results.
“In my experience with transcranial Doppler, I find shunts in patients every day that have not been seen with transthoracic echo,” he commented.
He noted that a previous meta-analysis has suggested a similar difference between TCD and transthoracic echo, but the current study provides prospectively collected data produced in a clinical trial setting and is therefore more reliable.
“What I hope comes from this is that more patients will be able to undergo transcranial Doppler, which is a far superior screening technique for identifying right-to-left shunts. There is so much evidence to support the use of transcranial Doppler, but with this new artificial-intelligence robotic device, we don’t need an expert to use it,” Dr. Rubin said.
He explained that finding a right-to-left shunt in stroke patients is particularly important, as it can direct treatment strategies to reduce future risk of recurrent strokes.
“If a patient has a large shunt, then they have a high risk of having another stroke, and the PFO should be closed.”
In this study, the robotic-assisted TCD detected three times as many large shunts that were considered “intervenable,” compared with transthoracic echo, identifying these shunts in 35 patients (27%) compared to just 13 (10%) with TTE.
“Of the 35 patients with intervenable shunts detected with robotic transcranial Doppler, TTE was completely negative in 18 of them and only suggested a small shunt in the others. So, the standard of care (TTE) missed half the patients with intervenable PFOs,” Dr. Rubin reported.
Study should ‘dramatically change’ practice
Commenting on the study, Patrick Lyden, MD, professor of physiology and neuroscience and of neurology, University of Southern California, Los Angeles, said: “Most clinicians hesitate to use transcranial Doppler given the need for specialized technical expertise to obtain a reliable result. This study showed that a robotic transcranial Doppler device – which can be applied by any cardiac non-invasive lab technician – provides reliable and rigorous data.”
He added: “This result will dramatically change the typical evaluation of patients with suspected PFO: In place of an invasive transesophageal echo that requires anesthesia and a cardiologist, most patients can have a non-invasive, robotic-guided transcranial Doppler and get the same diagnostic benefit.”
Dr. Lyden also pointed out that the cost of TCD is typically one-tenth that of TEE, although he said the cost of the robotic guided TCD “is not clear.”
A representative of the company that makes the robotic assisted device, NovaSignal, says the cost of the equipment is approximately $250,000, but “understanding the importance of the technology, we work with each hospital to meet their unique needs.”
The company adds that it currently has “over 45 commercial solutions deployed across 25 centers with 3-4 times growth expected year over year.”
The study was supported by NovaSignal, the company which makes the robotic device. Dr. Rubin reports acting as a consultant for the NovaSignal.
A version of this article first appeared on Medscape.com.
FROM ISC 2022
Liquid embolism of AVM tied to high cure rate
new observational data suggest. In a prospective, real-world study of more than 100 patients, use of the Onyx system was associated with a cure rate of 86% for cAVMs smaller than 3 cm.
“Endovascular treatment using Onyx is able to achieve, on its own, a very efficient cure rate with a low morbidity and mortality rate,” said investigator Laurent Spelle, MD, PhD, professor of neuroradiology at Paris-Saclay University and chair of NEURI, the Brain Vascular Center, Bicêtre Hospital, also in Paris.
Dr. Spelle presented the findings at the International Stroke Conference sponsored by the American Heart Association.
Prospective, multicenter study
Currently, the main treatment options for cAVM are embolization, neurosurgery, and radiosurgery. The Onyx liquid system, one method of providing embolization, uses a biocompatible ethylene vinyl alcohol copolymer.
It has been used in Europe for 22 years as a curative treatment and as a treatment before radiosurgery or neurosurgery. In the United States, Onyx is indicated for presurgical and preradiotherapy treatment only.
For this analysis, the researchers conducted a prospective, multicenter study to evaluate the long-term safety and efficacy of Onyx for the embolization of cAVM as curative treatment or preoperative preparation.
They enrolled 165 patients in the nonrandomized, observational study, which was conducted at 15 hospitals in France. Eligible participants had an untreated cAVM.
Patients were assigned to one of three groups, according to the hospital’s standard of care. One group underwent embolization with Onyx as curative treatment, one received Onyx as preparation for neurosurgery, and one underwent embolization with Onyx as preparation for radiosurgery.
The study’s safety endpoints were device- and procedure-related serious adverse events at 1 month after each embolization. The efficacy endpoints were recovery at 12 months after the last embolization or neurosurgery, or at a minimum of 36 months after radiosurgery.
The researchers defined morbidity as a worsening of modified Rankin Scale score of 2 or more points for patients presenting with baseline mRS of 0 or 1, or a worsening of 1 or more points for patients with an mRS of 2 or greater at baseline. An independent clinical events committee and core laboratory adjudicated the results.
‘A fantastic result’
In all, 140 patients were prospectively included, and 212 embolization procedures were performed. The population’s mean age was 41.4 years, and 60% of participants were men. About 61% of patients presented with symptoms, the most common of which were progressive neurologic deficit (41.2%) and headache (36.5%).
Approximately 64% of the cAVMs were ruptured. Most (75.7%) were smaller than 3 cm, and the remainder were between 3 and 6 cm. Most patients (59.3%) did not have an aneurysm.
Eight (3.8%) adverse events were associated with the use of Onyx. The rate of procedure-related neurologic serious adverse events was 7.1% within 1 month post embolization. Three deaths occurred (2.1%), one of which was considered device or procedure related.
A total of 87 patients underwent embolization alone, 14 of whom did not complete the study (2 died, 5 were lost to follow-up, and 7 withdrew). Of the 73 who completed the study, 58 (79.5%) had complete occlusion and full recovery at last follow-up. An additional 6.8% had 99% occlusion.
In addition, 3.4% of the population had significant morbidity, and 18.4% presented at baseline with mRS scores of 3-5. Of the latter group, 81.3% had mRS scores of 0-2 at last visit.
Of 21 patients who underwent subsequent neurosurgery, 18 completed follow-up. Of this group, 94.4% had complete occlusion. Of 32 patients receiving subsequent radiosurgery, 54.8% had complete occlusion, which was “a little bit disappointing,” said Dr. Spelle.
Overall, most patients (92.9%) had improved or stable mRS score. The overall mortality rate was 2.9%, and the rate of significant morbidity was 4.3%.
The rate of improved or stable mRS score was 94.3% for patients who underwent embolization alone, 85.7% for patients who also underwent neurosurgery, and 93.75% for patients who also underwent radiosurgery.
The mortality rate was 3.4% for patients who underwent embolization alone, 4.8% for patients who also underwent neurosurgery, and 0% for patients who also underwent radiosurgery.
The rate of significant morbidity was 2.3% for patients who underwent embolization alone, 9.5% for those who also underwent neurosurgery, and 6.25% for those who also underwent radiosurgery.
“We knew that this treatment was very effective, but this effectiveness was only known in a limited number of centers with a very high level of expertise,” said Dr. Spelle. “We were very pleasantly surprised that a larger-scale, multicenter study conducted in 15 different hospitals in France could achieve such a fantastic result.”
The study sites, however, were all departments in university hospitals with great experience in endovascular treatment of cAVM, he added.
Effective in unruptured AVMs?
Commenting on the findings, Mitchell Elkind, MD, professor of neurology and epidemiology, Columbia University, New York, said: “Arteriovenous malformations remain a relatively uncommon but serious cerebrovascular disorder. Any additional tool in the armamentarium to treat these lesions is welcome.”
The study results are encouraging, said Dr. Elkind, who was not involved in the study. They suggest that Onyx embolization can play an important role in the care of these patients. The treatment is associated with “low morbidity and excellent efficacy, particularly in combination with other surgical and radiographic approaches.”
The lack of a direct comparison with alternative embolization materials is a limitation of the study, however. “It is hard to compare Onyx to other agents based on these results,” said Dr. Elkind.
“It is also notable that one-third of the patients in the study had unruptured AVMs, which at least in one randomized trial, ARUBA, were not clearly shown to benefit from an intervention at all,” he continued.
It would have been valuable for the researchers to stratify the study results by ruptured versus unruptured AVMs, Dr. Elkind said.
The study was funded by Medtronic. Dr. Spelle reported receiving honoraria from the company. Dr. Elkind disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
new observational data suggest. In a prospective, real-world study of more than 100 patients, use of the Onyx system was associated with a cure rate of 86% for cAVMs smaller than 3 cm.
“Endovascular treatment using Onyx is able to achieve, on its own, a very efficient cure rate with a low morbidity and mortality rate,” said investigator Laurent Spelle, MD, PhD, professor of neuroradiology at Paris-Saclay University and chair of NEURI, the Brain Vascular Center, Bicêtre Hospital, also in Paris.
Dr. Spelle presented the findings at the International Stroke Conference sponsored by the American Heart Association.
Prospective, multicenter study
Currently, the main treatment options for cAVM are embolization, neurosurgery, and radiosurgery. The Onyx liquid system, one method of providing embolization, uses a biocompatible ethylene vinyl alcohol copolymer.
It has been used in Europe for 22 years as a curative treatment and as a treatment before radiosurgery or neurosurgery. In the United States, Onyx is indicated for presurgical and preradiotherapy treatment only.
For this analysis, the researchers conducted a prospective, multicenter study to evaluate the long-term safety and efficacy of Onyx for the embolization of cAVM as curative treatment or preoperative preparation.
They enrolled 165 patients in the nonrandomized, observational study, which was conducted at 15 hospitals in France. Eligible participants had an untreated cAVM.
Patients were assigned to one of three groups, according to the hospital’s standard of care. One group underwent embolization with Onyx as curative treatment, one received Onyx as preparation for neurosurgery, and one underwent embolization with Onyx as preparation for radiosurgery.
The study’s safety endpoints were device- and procedure-related serious adverse events at 1 month after each embolization. The efficacy endpoints were recovery at 12 months after the last embolization or neurosurgery, or at a minimum of 36 months after radiosurgery.
The researchers defined morbidity as a worsening of modified Rankin Scale score of 2 or more points for patients presenting with baseline mRS of 0 or 1, or a worsening of 1 or more points for patients with an mRS of 2 or greater at baseline. An independent clinical events committee and core laboratory adjudicated the results.
‘A fantastic result’
In all, 140 patients were prospectively included, and 212 embolization procedures were performed. The population’s mean age was 41.4 years, and 60% of participants were men. About 61% of patients presented with symptoms, the most common of which were progressive neurologic deficit (41.2%) and headache (36.5%).
Approximately 64% of the cAVMs were ruptured. Most (75.7%) were smaller than 3 cm, and the remainder were between 3 and 6 cm. Most patients (59.3%) did not have an aneurysm.
Eight (3.8%) adverse events were associated with the use of Onyx. The rate of procedure-related neurologic serious adverse events was 7.1% within 1 month post embolization. Three deaths occurred (2.1%), one of which was considered device or procedure related.
A total of 87 patients underwent embolization alone, 14 of whom did not complete the study (2 died, 5 were lost to follow-up, and 7 withdrew). Of the 73 who completed the study, 58 (79.5%) had complete occlusion and full recovery at last follow-up. An additional 6.8% had 99% occlusion.
In addition, 3.4% of the population had significant morbidity, and 18.4% presented at baseline with mRS scores of 3-5. Of the latter group, 81.3% had mRS scores of 0-2 at last visit.
Of 21 patients who underwent subsequent neurosurgery, 18 completed follow-up. Of this group, 94.4% had complete occlusion. Of 32 patients receiving subsequent radiosurgery, 54.8% had complete occlusion, which was “a little bit disappointing,” said Dr. Spelle.
Overall, most patients (92.9%) had improved or stable mRS score. The overall mortality rate was 2.9%, and the rate of significant morbidity was 4.3%.
The rate of improved or stable mRS score was 94.3% for patients who underwent embolization alone, 85.7% for patients who also underwent neurosurgery, and 93.75% for patients who also underwent radiosurgery.
The mortality rate was 3.4% for patients who underwent embolization alone, 4.8% for patients who also underwent neurosurgery, and 0% for patients who also underwent radiosurgery.
The rate of significant morbidity was 2.3% for patients who underwent embolization alone, 9.5% for those who also underwent neurosurgery, and 6.25% for those who also underwent radiosurgery.
“We knew that this treatment was very effective, but this effectiveness was only known in a limited number of centers with a very high level of expertise,” said Dr. Spelle. “We were very pleasantly surprised that a larger-scale, multicenter study conducted in 15 different hospitals in France could achieve such a fantastic result.”
The study sites, however, were all departments in university hospitals with great experience in endovascular treatment of cAVM, he added.
Effective in unruptured AVMs?
Commenting on the findings, Mitchell Elkind, MD, professor of neurology and epidemiology, Columbia University, New York, said: “Arteriovenous malformations remain a relatively uncommon but serious cerebrovascular disorder. Any additional tool in the armamentarium to treat these lesions is welcome.”
The study results are encouraging, said Dr. Elkind, who was not involved in the study. They suggest that Onyx embolization can play an important role in the care of these patients. The treatment is associated with “low morbidity and excellent efficacy, particularly in combination with other surgical and radiographic approaches.”
The lack of a direct comparison with alternative embolization materials is a limitation of the study, however. “It is hard to compare Onyx to other agents based on these results,” said Dr. Elkind.
“It is also notable that one-third of the patients in the study had unruptured AVMs, which at least in one randomized trial, ARUBA, were not clearly shown to benefit from an intervention at all,” he continued.
It would have been valuable for the researchers to stratify the study results by ruptured versus unruptured AVMs, Dr. Elkind said.
The study was funded by Medtronic. Dr. Spelle reported receiving honoraria from the company. Dr. Elkind disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
new observational data suggest. In a prospective, real-world study of more than 100 patients, use of the Onyx system was associated with a cure rate of 86% for cAVMs smaller than 3 cm.
“Endovascular treatment using Onyx is able to achieve, on its own, a very efficient cure rate with a low morbidity and mortality rate,” said investigator Laurent Spelle, MD, PhD, professor of neuroradiology at Paris-Saclay University and chair of NEURI, the Brain Vascular Center, Bicêtre Hospital, also in Paris.
Dr. Spelle presented the findings at the International Stroke Conference sponsored by the American Heart Association.
Prospective, multicenter study
Currently, the main treatment options for cAVM are embolization, neurosurgery, and radiosurgery. The Onyx liquid system, one method of providing embolization, uses a biocompatible ethylene vinyl alcohol copolymer.
It has been used in Europe for 22 years as a curative treatment and as a treatment before radiosurgery or neurosurgery. In the United States, Onyx is indicated for presurgical and preradiotherapy treatment only.
For this analysis, the researchers conducted a prospective, multicenter study to evaluate the long-term safety and efficacy of Onyx for the embolization of cAVM as curative treatment or preoperative preparation.
They enrolled 165 patients in the nonrandomized, observational study, which was conducted at 15 hospitals in France. Eligible participants had an untreated cAVM.
Patients were assigned to one of three groups, according to the hospital’s standard of care. One group underwent embolization with Onyx as curative treatment, one received Onyx as preparation for neurosurgery, and one underwent embolization with Onyx as preparation for radiosurgery.
The study’s safety endpoints were device- and procedure-related serious adverse events at 1 month after each embolization. The efficacy endpoints were recovery at 12 months after the last embolization or neurosurgery, or at a minimum of 36 months after radiosurgery.
The researchers defined morbidity as a worsening of modified Rankin Scale score of 2 or more points for patients presenting with baseline mRS of 0 or 1, or a worsening of 1 or more points for patients with an mRS of 2 or greater at baseline. An independent clinical events committee and core laboratory adjudicated the results.
‘A fantastic result’
In all, 140 patients were prospectively included, and 212 embolization procedures were performed. The population’s mean age was 41.4 years, and 60% of participants were men. About 61% of patients presented with symptoms, the most common of which were progressive neurologic deficit (41.2%) and headache (36.5%).
Approximately 64% of the cAVMs were ruptured. Most (75.7%) were smaller than 3 cm, and the remainder were between 3 and 6 cm. Most patients (59.3%) did not have an aneurysm.
Eight (3.8%) adverse events were associated with the use of Onyx. The rate of procedure-related neurologic serious adverse events was 7.1% within 1 month post embolization. Three deaths occurred (2.1%), one of which was considered device or procedure related.
A total of 87 patients underwent embolization alone, 14 of whom did not complete the study (2 died, 5 were lost to follow-up, and 7 withdrew). Of the 73 who completed the study, 58 (79.5%) had complete occlusion and full recovery at last follow-up. An additional 6.8% had 99% occlusion.
In addition, 3.4% of the population had significant morbidity, and 18.4% presented at baseline with mRS scores of 3-5. Of the latter group, 81.3% had mRS scores of 0-2 at last visit.
Of 21 patients who underwent subsequent neurosurgery, 18 completed follow-up. Of this group, 94.4% had complete occlusion. Of 32 patients receiving subsequent radiosurgery, 54.8% had complete occlusion, which was “a little bit disappointing,” said Dr. Spelle.
Overall, most patients (92.9%) had improved or stable mRS score. The overall mortality rate was 2.9%, and the rate of significant morbidity was 4.3%.
The rate of improved or stable mRS score was 94.3% for patients who underwent embolization alone, 85.7% for patients who also underwent neurosurgery, and 93.75% for patients who also underwent radiosurgery.
The mortality rate was 3.4% for patients who underwent embolization alone, 4.8% for patients who also underwent neurosurgery, and 0% for patients who also underwent radiosurgery.
The rate of significant morbidity was 2.3% for patients who underwent embolization alone, 9.5% for those who also underwent neurosurgery, and 6.25% for those who also underwent radiosurgery.
“We knew that this treatment was very effective, but this effectiveness was only known in a limited number of centers with a very high level of expertise,” said Dr. Spelle. “We were very pleasantly surprised that a larger-scale, multicenter study conducted in 15 different hospitals in France could achieve such a fantastic result.”
The study sites, however, were all departments in university hospitals with great experience in endovascular treatment of cAVM, he added.
Effective in unruptured AVMs?
Commenting on the findings, Mitchell Elkind, MD, professor of neurology and epidemiology, Columbia University, New York, said: “Arteriovenous malformations remain a relatively uncommon but serious cerebrovascular disorder. Any additional tool in the armamentarium to treat these lesions is welcome.”
The study results are encouraging, said Dr. Elkind, who was not involved in the study. They suggest that Onyx embolization can play an important role in the care of these patients. The treatment is associated with “low morbidity and excellent efficacy, particularly in combination with other surgical and radiographic approaches.”
The lack of a direct comparison with alternative embolization materials is a limitation of the study, however. “It is hard to compare Onyx to other agents based on these results,” said Dr. Elkind.
“It is also notable that one-third of the patients in the study had unruptured AVMs, which at least in one randomized trial, ARUBA, were not clearly shown to benefit from an intervention at all,” he continued.
It would have been valuable for the researchers to stratify the study results by ruptured versus unruptured AVMs, Dr. Elkind said.
The study was funded by Medtronic. Dr. Spelle reported receiving honoraria from the company. Dr. Elkind disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ISC 2022
Tenecteplase for stroke thrombolysis up to 24 hours?
, a new trial from China suggests.
The phase 2a CHABLIS trial was presented at the International Stroke Conference by Xin Cheng, MD, associate professor of neurology at the Huashan Hospital of Fudan University and the National Center for Neurological Disorders in Shanghai, China.
“These results are the first to be reported with tenecteplase in the extended time window and suggest that it may be feasible to extend the time window of intravenous thrombolysis to 24 hours after last known well through perfusion imaging selection,” she concluded at the conference presented by the American Stroke Association, a division of the American Heart Association.
Dr. Cheng noted that alteplase (tissue plasminogen activator) is the standard of care for thrombolysis in stroke, with a time window of up to 4.5 hours after stroke onset. However, the recent EXTEND trial suggested benefit of alteplase in patients who were between 4.5 and 9 hours of stroke onset and who had hypoperfused but salvageable regions of brain detected on automated perfusion imaging.
Tenecteplase is a genetically modified variant of alteplase. It has received regulatory approval for treatment of myocardial infarction. Dr. Cheng said there is increasing interest in tenecteplase as an alternative to alteplase, mainly because of its practical advantages (single bolus, rather than 1-hour infusion) and its having a number of hypothetical advantages over alteplase, including greater fibrin specificity and lesser likelihood of fibrinogen depletion.
Until now, studies of tenecteplase in stroke have included patients in the traditional time window, which has been no longer than 6 hours from stroke onset, she added.
For the current CHABLIS trial, the Chinese researchers investigated the use of tenecteplase administered to ischemic stroke patients at 4.5-24 hours from time of their being last seen well who were selected by significant penumbral mismatch on perfusion imaging. The trial included 86 patients who had an anterior large-vessel occlusion or severe stenosis identified on head and neck CT angiography and penumbral mismatch on CT perfusion imaging. They were randomized to one of two doses of tenecteplase, 0.25 mg/kg or 0.32 mg/kg.
The primary outcome was the achievement of reperfusion without symptomatic intracranial hemorrhage at 24-48 hours after thrombolysis. This occurred in 32% of the 0.25-mg/kg group versus 23.3% of the 0.32-mg/kg group.
Recanalization at 4-6 hours occurred in 44% of both groups.
In terms of neurologic outcomes, an excellent functional outcome, defined as a Modified Rankin Scale (mRS) score of 0-1 at 90 days, was achieved in 28% of the 0.25-mg/kg group and 49% of the 0.32-mg/kg group. A good functional outcome (mRS, 0-2) occurred in 46% of the 0.25-mg/kg group versus 60% of the 0.32-mg/kg group.
Limitations of the study included a small sample size and the lack of a control group. In addition, the study included only Chinese patients, who are known to have different stroke etiologies in comparison with White patients, Dr. Cheng noted.
In the subset of patients who received tenecteplase and who underwent endovascular therapy, fewer patients (8.8%) reached the primary outcome measure of reperfusion without symptomatic ICH, compared with those who received only tenecteplase (40.4%).
“In our study, tenecteplase seems to be quite effective and safe in patients who do not need endovascular therapy,” Dr. Cheng said. “More research is needed to understand why tenecteplase was less effective in restoring blood flow and more likely to result in symptomatic brain bleeding among those who had endovascular therapy.”
The researchers have now started a phase 2b trial, CHABLIS-2. This is a randomized, multicenter, controlled, open-label study of the 0.25-mg/kg dose of tenecteplase.
Commenting on the current study at an ISC press conference, Tudor G. Jovin, MD, chair of neurology at Cooper University Hospital, Cherry Hill, New Jersey, said: “This is very important study looking at the question of using thrombolysis out to 24 hours, and it does suggest a benefit, but we don’t know the best dose yet.”
He noted that his hospital system has already switched from alteplase to tenecteplase in the treatment of stroke, and several other centers are also making this switch. “In our center, we use the 0.25-mg/kg dose, but we don’t routinely treat patients beyond the 4.5-hour time window,” Dr. Jovin reported.
“The signals are there for a longer treatment window,” he said. “But this study was not aiming to directly answer whether tenecteplase is better than no treatment or alteplase, or its use with endovascular therapy.”
Noting that there are similar randomized trials ongoing in the United States and other countries exploring the same doses of tenecteplase, he said he thought the “dose and approach is applicable to U.S. practice.”
The CHABLIS study was funded by national key research and development program of China from the Science and Technology Ministry. Tenecteplase was provided by Guangzhou Recomgen Biotech.
A version of this article first appeared on Medscape.com.
, a new trial from China suggests.
The phase 2a CHABLIS trial was presented at the International Stroke Conference by Xin Cheng, MD, associate professor of neurology at the Huashan Hospital of Fudan University and the National Center for Neurological Disorders in Shanghai, China.
“These results are the first to be reported with tenecteplase in the extended time window and suggest that it may be feasible to extend the time window of intravenous thrombolysis to 24 hours after last known well through perfusion imaging selection,” she concluded at the conference presented by the American Stroke Association, a division of the American Heart Association.
Dr. Cheng noted that alteplase (tissue plasminogen activator) is the standard of care for thrombolysis in stroke, with a time window of up to 4.5 hours after stroke onset. However, the recent EXTEND trial suggested benefit of alteplase in patients who were between 4.5 and 9 hours of stroke onset and who had hypoperfused but salvageable regions of brain detected on automated perfusion imaging.
Tenecteplase is a genetically modified variant of alteplase. It has received regulatory approval for treatment of myocardial infarction. Dr. Cheng said there is increasing interest in tenecteplase as an alternative to alteplase, mainly because of its practical advantages (single bolus, rather than 1-hour infusion) and its having a number of hypothetical advantages over alteplase, including greater fibrin specificity and lesser likelihood of fibrinogen depletion.
Until now, studies of tenecteplase in stroke have included patients in the traditional time window, which has been no longer than 6 hours from stroke onset, she added.
For the current CHABLIS trial, the Chinese researchers investigated the use of tenecteplase administered to ischemic stroke patients at 4.5-24 hours from time of their being last seen well who were selected by significant penumbral mismatch on perfusion imaging. The trial included 86 patients who had an anterior large-vessel occlusion or severe stenosis identified on head and neck CT angiography and penumbral mismatch on CT perfusion imaging. They were randomized to one of two doses of tenecteplase, 0.25 mg/kg or 0.32 mg/kg.
The primary outcome was the achievement of reperfusion without symptomatic intracranial hemorrhage at 24-48 hours after thrombolysis. This occurred in 32% of the 0.25-mg/kg group versus 23.3% of the 0.32-mg/kg group.
Recanalization at 4-6 hours occurred in 44% of both groups.
In terms of neurologic outcomes, an excellent functional outcome, defined as a Modified Rankin Scale (mRS) score of 0-1 at 90 days, was achieved in 28% of the 0.25-mg/kg group and 49% of the 0.32-mg/kg group. A good functional outcome (mRS, 0-2) occurred in 46% of the 0.25-mg/kg group versus 60% of the 0.32-mg/kg group.
Limitations of the study included a small sample size and the lack of a control group. In addition, the study included only Chinese patients, who are known to have different stroke etiologies in comparison with White patients, Dr. Cheng noted.
In the subset of patients who received tenecteplase and who underwent endovascular therapy, fewer patients (8.8%) reached the primary outcome measure of reperfusion without symptomatic ICH, compared with those who received only tenecteplase (40.4%).
“In our study, tenecteplase seems to be quite effective and safe in patients who do not need endovascular therapy,” Dr. Cheng said. “More research is needed to understand why tenecteplase was less effective in restoring blood flow and more likely to result in symptomatic brain bleeding among those who had endovascular therapy.”
The researchers have now started a phase 2b trial, CHABLIS-2. This is a randomized, multicenter, controlled, open-label study of the 0.25-mg/kg dose of tenecteplase.
Commenting on the current study at an ISC press conference, Tudor G. Jovin, MD, chair of neurology at Cooper University Hospital, Cherry Hill, New Jersey, said: “This is very important study looking at the question of using thrombolysis out to 24 hours, and it does suggest a benefit, but we don’t know the best dose yet.”
He noted that his hospital system has already switched from alteplase to tenecteplase in the treatment of stroke, and several other centers are also making this switch. “In our center, we use the 0.25-mg/kg dose, but we don’t routinely treat patients beyond the 4.5-hour time window,” Dr. Jovin reported.
“The signals are there for a longer treatment window,” he said. “But this study was not aiming to directly answer whether tenecteplase is better than no treatment or alteplase, or its use with endovascular therapy.”
Noting that there are similar randomized trials ongoing in the United States and other countries exploring the same doses of tenecteplase, he said he thought the “dose and approach is applicable to U.S. practice.”
The CHABLIS study was funded by national key research and development program of China from the Science and Technology Ministry. Tenecteplase was provided by Guangzhou Recomgen Biotech.
A version of this article first appeared on Medscape.com.
, a new trial from China suggests.
The phase 2a CHABLIS trial was presented at the International Stroke Conference by Xin Cheng, MD, associate professor of neurology at the Huashan Hospital of Fudan University and the National Center for Neurological Disorders in Shanghai, China.
“These results are the first to be reported with tenecteplase in the extended time window and suggest that it may be feasible to extend the time window of intravenous thrombolysis to 24 hours after last known well through perfusion imaging selection,” she concluded at the conference presented by the American Stroke Association, a division of the American Heart Association.
Dr. Cheng noted that alteplase (tissue plasminogen activator) is the standard of care for thrombolysis in stroke, with a time window of up to 4.5 hours after stroke onset. However, the recent EXTEND trial suggested benefit of alteplase in patients who were between 4.5 and 9 hours of stroke onset and who had hypoperfused but salvageable regions of brain detected on automated perfusion imaging.
Tenecteplase is a genetically modified variant of alteplase. It has received regulatory approval for treatment of myocardial infarction. Dr. Cheng said there is increasing interest in tenecteplase as an alternative to alteplase, mainly because of its practical advantages (single bolus, rather than 1-hour infusion) and its having a number of hypothetical advantages over alteplase, including greater fibrin specificity and lesser likelihood of fibrinogen depletion.
Until now, studies of tenecteplase in stroke have included patients in the traditional time window, which has been no longer than 6 hours from stroke onset, she added.
For the current CHABLIS trial, the Chinese researchers investigated the use of tenecteplase administered to ischemic stroke patients at 4.5-24 hours from time of their being last seen well who were selected by significant penumbral mismatch on perfusion imaging. The trial included 86 patients who had an anterior large-vessel occlusion or severe stenosis identified on head and neck CT angiography and penumbral mismatch on CT perfusion imaging. They were randomized to one of two doses of tenecteplase, 0.25 mg/kg or 0.32 mg/kg.
The primary outcome was the achievement of reperfusion without symptomatic intracranial hemorrhage at 24-48 hours after thrombolysis. This occurred in 32% of the 0.25-mg/kg group versus 23.3% of the 0.32-mg/kg group.
Recanalization at 4-6 hours occurred in 44% of both groups.
In terms of neurologic outcomes, an excellent functional outcome, defined as a Modified Rankin Scale (mRS) score of 0-1 at 90 days, was achieved in 28% of the 0.25-mg/kg group and 49% of the 0.32-mg/kg group. A good functional outcome (mRS, 0-2) occurred in 46% of the 0.25-mg/kg group versus 60% of the 0.32-mg/kg group.
Limitations of the study included a small sample size and the lack of a control group. In addition, the study included only Chinese patients, who are known to have different stroke etiologies in comparison with White patients, Dr. Cheng noted.
In the subset of patients who received tenecteplase and who underwent endovascular therapy, fewer patients (8.8%) reached the primary outcome measure of reperfusion without symptomatic ICH, compared with those who received only tenecteplase (40.4%).
“In our study, tenecteplase seems to be quite effective and safe in patients who do not need endovascular therapy,” Dr. Cheng said. “More research is needed to understand why tenecteplase was less effective in restoring blood flow and more likely to result in symptomatic brain bleeding among those who had endovascular therapy.”
The researchers have now started a phase 2b trial, CHABLIS-2. This is a randomized, multicenter, controlled, open-label study of the 0.25-mg/kg dose of tenecteplase.
Commenting on the current study at an ISC press conference, Tudor G. Jovin, MD, chair of neurology at Cooper University Hospital, Cherry Hill, New Jersey, said: “This is very important study looking at the question of using thrombolysis out to 24 hours, and it does suggest a benefit, but we don’t know the best dose yet.”
He noted that his hospital system has already switched from alteplase to tenecteplase in the treatment of stroke, and several other centers are also making this switch. “In our center, we use the 0.25-mg/kg dose, but we don’t routinely treat patients beyond the 4.5-hour time window,” Dr. Jovin reported.
“The signals are there for a longer treatment window,” he said. “But this study was not aiming to directly answer whether tenecteplase is better than no treatment or alteplase, or its use with endovascular therapy.”
Noting that there are similar randomized trials ongoing in the United States and other countries exploring the same doses of tenecteplase, he said he thought the “dose and approach is applicable to U.S. practice.”
The CHABLIS study was funded by national key research and development program of China from the Science and Technology Ministry. Tenecteplase was provided by Guangzhou Recomgen Biotech.
A version of this article first appeared on Medscape.com.
FROM ISC 2022
Tirofiban does not improve outcomes of endovascular treatment in stroke
, new data suggest.
In a randomized, phase 3 trial of more than 900 patients with acute ischemic stroke who underwent endovascular treatment, the median Modified Rankin Scale (mRS) score at 90 days was 3 both in patients who received tirofiban and those who received placebo.
“There was treatment-effect modification by stroke etiology, where patients with large-artery atherosclerosis [LAA] seemed to benefit from the treatment,” said investigator Raul Nogueira, MD, director of the University of Pittsburgh Medical Center Stroke Institute, during his presentation. “Tirofiban may improve endovascular treatment outcomes in LAA strokes. This obviously requires further investigation in future trials to confirm these findings.”
Results of the RESCUE BT trial were presented at the hybrid International Stroke Conference (ISC) 2022, which was held in New Orleans, Louisiana, and online.
Multicenter trial
Endovascular treatment greatly increases the rate of reperfusion and improves functional outcomes in patients with large-vessel occlusion stroke, the researchers note. But mechanical thrombectomy devices may injure the vessel wall, which can lead to clot formation and vessel reocclusion.
Platelet inhibition is a potential tactic for improving outcomes in this setting. Tirofiban, a glycoprotein IIb/IIIa receptor inhibitor, is a reversible antiplatelet drug with a rapid onset of action and a short half-life. The drug’s safety and efficacy in acute coronary syndrome are well established. There has been little evidence to date, however, on whether tirofiban improves outcomes among patients with large-vessel occlusion stroke.
The investigators conducted the Endovascular Treatment With Versus Without Tirofiban for Stroke Patients With Large Vessel Occlusion (RESCUE BT) trial to evaluate the safety and efficacy of IV tirofiban therapy before endovascular treatment in patients with large-vessel occlusion stroke. They recruited consecutive patients at 55 thrombectomy-capable hospitals in China.
Eligible patients were aged 18 years or older and presented within 24 hours of the time they were last seen when well. Baseline National Institutes of Health Stroke Scale (NIHSS) score was required to be 30 or lower, and all patients were required to have plans to undergo endovascular treatment. Eligible patients also had a baseline Alberta Stroke Program Early CT Score of 6 or greater.
Patients were randomized in groups of equal size to placebo or tirofiban and stratified by NIHSS score and occlusion site. Tirofiban was administered in a 10-mcg/kg bolus followed by continuous infusion (0.15 mcg/kg per min) for 24 hours. All patients underwent rapid endovascular treatment.
At the 20th hour after treatment initiation, antiplatelets were administered orally. IV study drug was stopped at the 24th hour.
The study’s primary endpoint was disability level, as measured by overall distribution of the 90-day mRS score. The primary safety endpoints were symptomatic intracranial hemorrhage (ICH) at 48 hours and mortality at 90 days.
Increased ICH risk
The investigators screened 1,970 patients and enrolled 950 into their study. The population’s median age was 67 years, and 58.8% of participants were men. In all, 463 participants were randomly assigned to tirofiban, and 485 to placebo. Two patients withdrew consent, and none were lost to follow-up.
Baseline characteristics were well balanced in both groups. One difference, however, was that large-vessel occlusion was less prevalent in the tirofiban group (42.6%) than in the control group (49.1%).
The primary endpoint did not differ between treatment groups. The adjusted common odds ratio was 1.09 (P = .46). “There is perhaps a sign that there is maybe a favorable effect of tirofiban,” said Dr. Nogueira. “However, this did not reach statistical significance.”
The rates of symptomatic ICH and mortality at 90 days did not differ significantly between groups. There was a trend toward a higher rate of symptomatic ICH in the tirofiban group, however. Moreover, the rate of any ICH was 34.9% in the tirofiban group and 28.0% in the control group (P = .02).
In prespecified subgroup analysis, the researchers found that, among patients with large-vessel occlusion, the adjusted common odds ratio was 1.43 favoring tirofiban treatment. No other subgroups showed significant differences.
“In the intention-to-treat analysis, tirofiban did not improve clinical outcomes in the overall study population,” said Dr. Nogueira. “It did increase the rate of any ICH and potentially increased the rate of symptomatic ICH as well.”
The ongoing RESCUE BT2 trial is examining the safety and efficacy of tirofiban in patients with acute ischemic stroke with non–large-vessel occlusion. As of Jan. 20, 781 patients had been assigned randomly to treatment, said Dr. Nogueira.
Patient selection crucial
Louise McCullough, MD, PhD, professor and chair of neurology at the University of Texas Health Science Center at Houston, said that the study was well designed.
“The concern with any kind of platelet therapy or adjunctive therapy is hemorrhage,” said Dr. McCullough, who was not involved in the research. The results in the overall population support this concern.
The location of the trial sites may have influenced the results. “It was a multicenter trial, but it was predominantly done in Asia, and we know that there are higher levels of intracranial atherosclerosis in that population,” said Dr. McCullough.
The results indicate a potential benefit of tirofiban in patients with large-vessel occlusion, yet this finding raises practical questions. “It’s often difficult to know if these patients have atherosclerosis until you’re actually in the vessel,” said Dr. McCullough.
The findings may not have immediate practical implications. “I don’t think that in routine clinical practice it’s something that we would offer until we can decide how safe it is,” said Dr. McCullough. The question will be how to select the populations in whom the drug will have the most efficacy.
The study was funded by the National Natural Science Foundation of China, Army Medical University, and Lunan Pharmaceutical Group, the manufacturer of tirofiban. Dr. Nogueira reported holding stock in Brainomix, Viz-AI, Corindus Vascular Robotics, Vesalio, Viz-AI, and Ceretrieve. He has received research support from Corindus Vascular Robotics. Dr. Nogueira reported other financial relationships related to Stryker Neurovascular, Medtronic, Cerenovus, and Phenox. Dr. McCullough has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new data suggest.
In a randomized, phase 3 trial of more than 900 patients with acute ischemic stroke who underwent endovascular treatment, the median Modified Rankin Scale (mRS) score at 90 days was 3 both in patients who received tirofiban and those who received placebo.
“There was treatment-effect modification by stroke etiology, where patients with large-artery atherosclerosis [LAA] seemed to benefit from the treatment,” said investigator Raul Nogueira, MD, director of the University of Pittsburgh Medical Center Stroke Institute, during his presentation. “Tirofiban may improve endovascular treatment outcomes in LAA strokes. This obviously requires further investigation in future trials to confirm these findings.”
Results of the RESCUE BT trial were presented at the hybrid International Stroke Conference (ISC) 2022, which was held in New Orleans, Louisiana, and online.
Multicenter trial
Endovascular treatment greatly increases the rate of reperfusion and improves functional outcomes in patients with large-vessel occlusion stroke, the researchers note. But mechanical thrombectomy devices may injure the vessel wall, which can lead to clot formation and vessel reocclusion.
Platelet inhibition is a potential tactic for improving outcomes in this setting. Tirofiban, a glycoprotein IIb/IIIa receptor inhibitor, is a reversible antiplatelet drug with a rapid onset of action and a short half-life. The drug’s safety and efficacy in acute coronary syndrome are well established. There has been little evidence to date, however, on whether tirofiban improves outcomes among patients with large-vessel occlusion stroke.
The investigators conducted the Endovascular Treatment With Versus Without Tirofiban for Stroke Patients With Large Vessel Occlusion (RESCUE BT) trial to evaluate the safety and efficacy of IV tirofiban therapy before endovascular treatment in patients with large-vessel occlusion stroke. They recruited consecutive patients at 55 thrombectomy-capable hospitals in China.
Eligible patients were aged 18 years or older and presented within 24 hours of the time they were last seen when well. Baseline National Institutes of Health Stroke Scale (NIHSS) score was required to be 30 or lower, and all patients were required to have plans to undergo endovascular treatment. Eligible patients also had a baseline Alberta Stroke Program Early CT Score of 6 or greater.
Patients were randomized in groups of equal size to placebo or tirofiban and stratified by NIHSS score and occlusion site. Tirofiban was administered in a 10-mcg/kg bolus followed by continuous infusion (0.15 mcg/kg per min) for 24 hours. All patients underwent rapid endovascular treatment.
At the 20th hour after treatment initiation, antiplatelets were administered orally. IV study drug was stopped at the 24th hour.
The study’s primary endpoint was disability level, as measured by overall distribution of the 90-day mRS score. The primary safety endpoints were symptomatic intracranial hemorrhage (ICH) at 48 hours and mortality at 90 days.
Increased ICH risk
The investigators screened 1,970 patients and enrolled 950 into their study. The population’s median age was 67 years, and 58.8% of participants were men. In all, 463 participants were randomly assigned to tirofiban, and 485 to placebo. Two patients withdrew consent, and none were lost to follow-up.
Baseline characteristics were well balanced in both groups. One difference, however, was that large-vessel occlusion was less prevalent in the tirofiban group (42.6%) than in the control group (49.1%).
The primary endpoint did not differ between treatment groups. The adjusted common odds ratio was 1.09 (P = .46). “There is perhaps a sign that there is maybe a favorable effect of tirofiban,” said Dr. Nogueira. “However, this did not reach statistical significance.”
The rates of symptomatic ICH and mortality at 90 days did not differ significantly between groups. There was a trend toward a higher rate of symptomatic ICH in the tirofiban group, however. Moreover, the rate of any ICH was 34.9% in the tirofiban group and 28.0% in the control group (P = .02).
In prespecified subgroup analysis, the researchers found that, among patients with large-vessel occlusion, the adjusted common odds ratio was 1.43 favoring tirofiban treatment. No other subgroups showed significant differences.
“In the intention-to-treat analysis, tirofiban did not improve clinical outcomes in the overall study population,” said Dr. Nogueira. “It did increase the rate of any ICH and potentially increased the rate of symptomatic ICH as well.”
The ongoing RESCUE BT2 trial is examining the safety and efficacy of tirofiban in patients with acute ischemic stroke with non–large-vessel occlusion. As of Jan. 20, 781 patients had been assigned randomly to treatment, said Dr. Nogueira.
Patient selection crucial
Louise McCullough, MD, PhD, professor and chair of neurology at the University of Texas Health Science Center at Houston, said that the study was well designed.
“The concern with any kind of platelet therapy or adjunctive therapy is hemorrhage,” said Dr. McCullough, who was not involved in the research. The results in the overall population support this concern.
The location of the trial sites may have influenced the results. “It was a multicenter trial, but it was predominantly done in Asia, and we know that there are higher levels of intracranial atherosclerosis in that population,” said Dr. McCullough.
The results indicate a potential benefit of tirofiban in patients with large-vessel occlusion, yet this finding raises practical questions. “It’s often difficult to know if these patients have atherosclerosis until you’re actually in the vessel,” said Dr. McCullough.
The findings may not have immediate practical implications. “I don’t think that in routine clinical practice it’s something that we would offer until we can decide how safe it is,” said Dr. McCullough. The question will be how to select the populations in whom the drug will have the most efficacy.
The study was funded by the National Natural Science Foundation of China, Army Medical University, and Lunan Pharmaceutical Group, the manufacturer of tirofiban. Dr. Nogueira reported holding stock in Brainomix, Viz-AI, Corindus Vascular Robotics, Vesalio, Viz-AI, and Ceretrieve. He has received research support from Corindus Vascular Robotics. Dr. Nogueira reported other financial relationships related to Stryker Neurovascular, Medtronic, Cerenovus, and Phenox. Dr. McCullough has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new data suggest.
In a randomized, phase 3 trial of more than 900 patients with acute ischemic stroke who underwent endovascular treatment, the median Modified Rankin Scale (mRS) score at 90 days was 3 both in patients who received tirofiban and those who received placebo.
“There was treatment-effect modification by stroke etiology, where patients with large-artery atherosclerosis [LAA] seemed to benefit from the treatment,” said investigator Raul Nogueira, MD, director of the University of Pittsburgh Medical Center Stroke Institute, during his presentation. “Tirofiban may improve endovascular treatment outcomes in LAA strokes. This obviously requires further investigation in future trials to confirm these findings.”
Results of the RESCUE BT trial were presented at the hybrid International Stroke Conference (ISC) 2022, which was held in New Orleans, Louisiana, and online.
Multicenter trial
Endovascular treatment greatly increases the rate of reperfusion and improves functional outcomes in patients with large-vessel occlusion stroke, the researchers note. But mechanical thrombectomy devices may injure the vessel wall, which can lead to clot formation and vessel reocclusion.
Platelet inhibition is a potential tactic for improving outcomes in this setting. Tirofiban, a glycoprotein IIb/IIIa receptor inhibitor, is a reversible antiplatelet drug with a rapid onset of action and a short half-life. The drug’s safety and efficacy in acute coronary syndrome are well established. There has been little evidence to date, however, on whether tirofiban improves outcomes among patients with large-vessel occlusion stroke.
The investigators conducted the Endovascular Treatment With Versus Without Tirofiban for Stroke Patients With Large Vessel Occlusion (RESCUE BT) trial to evaluate the safety and efficacy of IV tirofiban therapy before endovascular treatment in patients with large-vessel occlusion stroke. They recruited consecutive patients at 55 thrombectomy-capable hospitals in China.
Eligible patients were aged 18 years or older and presented within 24 hours of the time they were last seen when well. Baseline National Institutes of Health Stroke Scale (NIHSS) score was required to be 30 or lower, and all patients were required to have plans to undergo endovascular treatment. Eligible patients also had a baseline Alberta Stroke Program Early CT Score of 6 or greater.
Patients were randomized in groups of equal size to placebo or tirofiban and stratified by NIHSS score and occlusion site. Tirofiban was administered in a 10-mcg/kg bolus followed by continuous infusion (0.15 mcg/kg per min) for 24 hours. All patients underwent rapid endovascular treatment.
At the 20th hour after treatment initiation, antiplatelets were administered orally. IV study drug was stopped at the 24th hour.
The study’s primary endpoint was disability level, as measured by overall distribution of the 90-day mRS score. The primary safety endpoints were symptomatic intracranial hemorrhage (ICH) at 48 hours and mortality at 90 days.
Increased ICH risk
The investigators screened 1,970 patients and enrolled 950 into their study. The population’s median age was 67 years, and 58.8% of participants were men. In all, 463 participants were randomly assigned to tirofiban, and 485 to placebo. Two patients withdrew consent, and none were lost to follow-up.
Baseline characteristics were well balanced in both groups. One difference, however, was that large-vessel occlusion was less prevalent in the tirofiban group (42.6%) than in the control group (49.1%).
The primary endpoint did not differ between treatment groups. The adjusted common odds ratio was 1.09 (P = .46). “There is perhaps a sign that there is maybe a favorable effect of tirofiban,” said Dr. Nogueira. “However, this did not reach statistical significance.”
The rates of symptomatic ICH and mortality at 90 days did not differ significantly between groups. There was a trend toward a higher rate of symptomatic ICH in the tirofiban group, however. Moreover, the rate of any ICH was 34.9% in the tirofiban group and 28.0% in the control group (P = .02).
In prespecified subgroup analysis, the researchers found that, among patients with large-vessel occlusion, the adjusted common odds ratio was 1.43 favoring tirofiban treatment. No other subgroups showed significant differences.
“In the intention-to-treat analysis, tirofiban did not improve clinical outcomes in the overall study population,” said Dr. Nogueira. “It did increase the rate of any ICH and potentially increased the rate of symptomatic ICH as well.”
The ongoing RESCUE BT2 trial is examining the safety and efficacy of tirofiban in patients with acute ischemic stroke with non–large-vessel occlusion. As of Jan. 20, 781 patients had been assigned randomly to treatment, said Dr. Nogueira.
Patient selection crucial
Louise McCullough, MD, PhD, professor and chair of neurology at the University of Texas Health Science Center at Houston, said that the study was well designed.
“The concern with any kind of platelet therapy or adjunctive therapy is hemorrhage,” said Dr. McCullough, who was not involved in the research. The results in the overall population support this concern.
The location of the trial sites may have influenced the results. “It was a multicenter trial, but it was predominantly done in Asia, and we know that there are higher levels of intracranial atherosclerosis in that population,” said Dr. McCullough.
The results indicate a potential benefit of tirofiban in patients with large-vessel occlusion, yet this finding raises practical questions. “It’s often difficult to know if these patients have atherosclerosis until you’re actually in the vessel,” said Dr. McCullough.
The findings may not have immediate practical implications. “I don’t think that in routine clinical practice it’s something that we would offer until we can decide how safe it is,” said Dr. McCullough. The question will be how to select the populations in whom the drug will have the most efficacy.
The study was funded by the National Natural Science Foundation of China, Army Medical University, and Lunan Pharmaceutical Group, the manufacturer of tirofiban. Dr. Nogueira reported holding stock in Brainomix, Viz-AI, Corindus Vascular Robotics, Vesalio, Viz-AI, and Ceretrieve. He has received research support from Corindus Vascular Robotics. Dr. Nogueira reported other financial relationships related to Stryker Neurovascular, Medtronic, Cerenovus, and Phenox. Dr. McCullough has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ISC 2022
Mixed results for cardiologists in stroke thrombectomy
Outcomes were mixed among ischemic stroke patients with large vessel occlusion who underwent thrombectomy by an interventional cardiologist as part of a multidisciplinary stroke team, in a single-center, prospective study from Poland.
Results from the 2-year experience show mechanical thrombectomy took longer when carried out by interventional cardiologists than by vascular surgeons and neuroradiologists (120 minutes vs. 105 minutes; P = .020).
The procedures were also less likely to achieve angiographic success, defined as a Thrombolysis in Cerebral Infarction (TICI) scale score of 2b or 3 (55.7% vs. 71.7%; P = .013), reported Krystian Wita, MD, PhD, Medical University of Silesia, Katowice, Poland, and colleagues.
The differences in duration and recanalization require further attention, they noted, and are related to a learning curve, more time dedicated to decision-making and, in some cases, needing a second opinion. Cardiologists performed 80 procedures compared with 116 for vascular surgeons and 52 for neuroradiologists, and treated twice as many patients with a previous stroke (13.9% vs. 6.5%).
Still, the interventional cardiologist- and noncardiologist-treated groups had similar functional independence at 3 months, defined by a modified Rankin Scale (mRS) score of 0 to 2 (44.4% vs. 54.8%; P = .275). Mortality was also similar at 3 months (31.3% vs. 28.0%; P = .595).
“This is the first analysis to prove the noninferiority of the cardiology services in the treatment of stroke with mechanical thrombectomy,” the authors reported in JACC: Cardiovascular Interventions.
But commenting for this news organization, J Mocco, MD, senior vice chair of neurosurgery and director of the Cerebrovascular Center at Mount Sinai Health System, New York, said this study isn’t designed as a noninferiority trial, is “grossly underpowered,” and the comparator cohort is not a gold standard comparator cohort.
“More importantly, they show that the cardiologists got significantly worse technical results and took longer, and we know that technical outcomes and the time to treatment are the two strongest predictors of outcome, which completely correlates with the fact that patients had 11% worse outcomes overall,” he said.
“It’s dumbfounding to me that this has been presented as evidence [that] an interventional cardiologist should be performing thrombectomy,” added Dr. Mocco, president-elect of the Society of NeuroInterventional Surgery.
Dr. Wita and coauthor Andrzej Kulach, MD, PhD, also with the Medical University of Silesia, told this news organization that timing is critical in mechanical thrombectomy (MT) and the sooner it’s performed, the better. But it cannot be performed by just any interventional cardiologist (IC).
“The IC must be trained in the procedure and cooperate with the neurologist to get good results,” they said. “We would like to stress that it is not a procedure for any cath lab and any cardiologist on duty. A network of cardiologists trained in MT must be organized and the stroke teams developed for the local unit to make the strategy reasonable and safe.”
The study was conducted from 2019 to 2020 and to participate, interventional cardiologists had to have performed a minimum of 700 angioplasties and 1,500 coronary angiographies and undergone complex training in thrombectomy, including 14-day training in a reference center and certified courses on a phantom and an animal model. They were also experienced in carotid angioplasty and participated as the second operators in neurointerventions.
“Considering the cardiologists are acting here in a multidisciplinary team led by neurologists, the findings are not surprising,” Dr. Wita and Dr. Kulach said. “What was surprising, is a certain level of skepticism among neurologists when cardiologists are to be involved in the procedure. We hope the quality of cardiology services will help to get over it.”
Major thrombectomy trials such as PRAGUE-16 have supported a role for interventional cardiologists to help meet demand for stroke thrombectomy. Dr. Wita and Dr. Kulach said there’s a lack of trained neuroradiologists and developed infrastructure for thrombectomy, whereas there’s a sufficient network of catheterization laboratories and trained cardiologists who could be involved.
The take-home message from the study, they said, is to “use the existing infrastructure to optimize the treatment of stroke. Building one from the very beginning is more time and resources-consuming.”
Dr. Mocco said a physician’s training is not a factor in the pathway to neurointerventional expertise, as long as they’re willing to put in the appropriate amount of specialization and training.
“There’s no way this represents a turf war or the neurology community somehow protecting its space, which is often used as a distraction, just like the idea that there’s not enough people,” he said. “It’s just not the case. Neurointervention is the most multispecialty space that I’m aware of.”
In the United States, at least, the problem isn’t a lack of resources or people to provide the service, but in getting patients to the correct hospitals, Dr. Mocco said. “We don’t have regionalized stroke care in the United States for the most part, so patients go to any hospital that says they provide stroke care rather than necessarily being triaged to capable centers that can provide the care.”
A 2021 Medicare analysis by Dr. Mocco and colleagues found that higher physician and hospital stroke thrombectomy volumes were associated with lower inpatient mortality and better outcomes.
Efforts are underway to regionalize care and delivery of patients in Los Angeles County and New York City, for example, where ambulances preferentially take patients with suspected large vessel occlusion to thrombectomy-capable stroke centers certified by independent organizations, Dr. Mocco said. In New York, “they’ve shown it has improved outcomes.”
Estêvão Carvalho de Campos Martins, MD, Hospital de Força Aérea do Galeão, Rio de Janeiro, and Fernando Luiz de Melo Bernardi, MD, Hospital Regional do Oeste, Chapecó, Brazil, noted in an accompanying editorial that the observational study is “hypothesis-generating only” and that the disconnect between technical and clinical outcomes is due to a type II error of low power.
They suggest that collaboration between specialties will be “essential for defining the optimal training program, so that ICs can reach solid procedural results.
“The accumulated experience with virtual simulation-based training for stroke could act as an educational accelerator but should be inserted in a prespecified program,” the editorialists said. “How to train and how to insert ICs into [an] MT interdisciplinary team is the current debate; meanwhile ICs are here, and many of them already contributing.”
Dr. Mocco is the principal investigator on research trials funded by Stryker Neurovascular, Microvention, and Penumbra; and is an investor in Cerebrotech, Imperative Care, Endostream, Viseon, BlinkTBI, Myra Medical, Serenity, Vastrax, NTI, RIST, Viz.ai , Synchron, Radical, and Truvic. He serves, or has recently served, as a consultant for: Cerebrotech, Viseon, Endostream, Vastrax, RIST, Synchron, Viz.ai , Perflow, and CVAid. Dr. Carvalho de Campos Martins and Dr. Luiz de Melo Bernardi have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Outcomes were mixed among ischemic stroke patients with large vessel occlusion who underwent thrombectomy by an interventional cardiologist as part of a multidisciplinary stroke team, in a single-center, prospective study from Poland.
Results from the 2-year experience show mechanical thrombectomy took longer when carried out by interventional cardiologists than by vascular surgeons and neuroradiologists (120 minutes vs. 105 minutes; P = .020).
The procedures were also less likely to achieve angiographic success, defined as a Thrombolysis in Cerebral Infarction (TICI) scale score of 2b or 3 (55.7% vs. 71.7%; P = .013), reported Krystian Wita, MD, PhD, Medical University of Silesia, Katowice, Poland, and colleagues.
The differences in duration and recanalization require further attention, they noted, and are related to a learning curve, more time dedicated to decision-making and, in some cases, needing a second opinion. Cardiologists performed 80 procedures compared with 116 for vascular surgeons and 52 for neuroradiologists, and treated twice as many patients with a previous stroke (13.9% vs. 6.5%).
Still, the interventional cardiologist- and noncardiologist-treated groups had similar functional independence at 3 months, defined by a modified Rankin Scale (mRS) score of 0 to 2 (44.4% vs. 54.8%; P = .275). Mortality was also similar at 3 months (31.3% vs. 28.0%; P = .595).
“This is the first analysis to prove the noninferiority of the cardiology services in the treatment of stroke with mechanical thrombectomy,” the authors reported in JACC: Cardiovascular Interventions.
But commenting for this news organization, J Mocco, MD, senior vice chair of neurosurgery and director of the Cerebrovascular Center at Mount Sinai Health System, New York, said this study isn’t designed as a noninferiority trial, is “grossly underpowered,” and the comparator cohort is not a gold standard comparator cohort.
“More importantly, they show that the cardiologists got significantly worse technical results and took longer, and we know that technical outcomes and the time to treatment are the two strongest predictors of outcome, which completely correlates with the fact that patients had 11% worse outcomes overall,” he said.
“It’s dumbfounding to me that this has been presented as evidence [that] an interventional cardiologist should be performing thrombectomy,” added Dr. Mocco, president-elect of the Society of NeuroInterventional Surgery.
Dr. Wita and coauthor Andrzej Kulach, MD, PhD, also with the Medical University of Silesia, told this news organization that timing is critical in mechanical thrombectomy (MT) and the sooner it’s performed, the better. But it cannot be performed by just any interventional cardiologist (IC).
“The IC must be trained in the procedure and cooperate with the neurologist to get good results,” they said. “We would like to stress that it is not a procedure for any cath lab and any cardiologist on duty. A network of cardiologists trained in MT must be organized and the stroke teams developed for the local unit to make the strategy reasonable and safe.”
The study was conducted from 2019 to 2020 and to participate, interventional cardiologists had to have performed a minimum of 700 angioplasties and 1,500 coronary angiographies and undergone complex training in thrombectomy, including 14-day training in a reference center and certified courses on a phantom and an animal model. They were also experienced in carotid angioplasty and participated as the second operators in neurointerventions.
“Considering the cardiologists are acting here in a multidisciplinary team led by neurologists, the findings are not surprising,” Dr. Wita and Dr. Kulach said. “What was surprising, is a certain level of skepticism among neurologists when cardiologists are to be involved in the procedure. We hope the quality of cardiology services will help to get over it.”
Major thrombectomy trials such as PRAGUE-16 have supported a role for interventional cardiologists to help meet demand for stroke thrombectomy. Dr. Wita and Dr. Kulach said there’s a lack of trained neuroradiologists and developed infrastructure for thrombectomy, whereas there’s a sufficient network of catheterization laboratories and trained cardiologists who could be involved.
The take-home message from the study, they said, is to “use the existing infrastructure to optimize the treatment of stroke. Building one from the very beginning is more time and resources-consuming.”
Dr. Mocco said a physician’s training is not a factor in the pathway to neurointerventional expertise, as long as they’re willing to put in the appropriate amount of specialization and training.
“There’s no way this represents a turf war or the neurology community somehow protecting its space, which is often used as a distraction, just like the idea that there’s not enough people,” he said. “It’s just not the case. Neurointervention is the most multispecialty space that I’m aware of.”
In the United States, at least, the problem isn’t a lack of resources or people to provide the service, but in getting patients to the correct hospitals, Dr. Mocco said. “We don’t have regionalized stroke care in the United States for the most part, so patients go to any hospital that says they provide stroke care rather than necessarily being triaged to capable centers that can provide the care.”
A 2021 Medicare analysis by Dr. Mocco and colleagues found that higher physician and hospital stroke thrombectomy volumes were associated with lower inpatient mortality and better outcomes.
Efforts are underway to regionalize care and delivery of patients in Los Angeles County and New York City, for example, where ambulances preferentially take patients with suspected large vessel occlusion to thrombectomy-capable stroke centers certified by independent organizations, Dr. Mocco said. In New York, “they’ve shown it has improved outcomes.”
Estêvão Carvalho de Campos Martins, MD, Hospital de Força Aérea do Galeão, Rio de Janeiro, and Fernando Luiz de Melo Bernardi, MD, Hospital Regional do Oeste, Chapecó, Brazil, noted in an accompanying editorial that the observational study is “hypothesis-generating only” and that the disconnect between technical and clinical outcomes is due to a type II error of low power.
They suggest that collaboration between specialties will be “essential for defining the optimal training program, so that ICs can reach solid procedural results.
“The accumulated experience with virtual simulation-based training for stroke could act as an educational accelerator but should be inserted in a prespecified program,” the editorialists said. “How to train and how to insert ICs into [an] MT interdisciplinary team is the current debate; meanwhile ICs are here, and many of them already contributing.”
Dr. Mocco is the principal investigator on research trials funded by Stryker Neurovascular, Microvention, and Penumbra; and is an investor in Cerebrotech, Imperative Care, Endostream, Viseon, BlinkTBI, Myra Medical, Serenity, Vastrax, NTI, RIST, Viz.ai , Synchron, Radical, and Truvic. He serves, or has recently served, as a consultant for: Cerebrotech, Viseon, Endostream, Vastrax, RIST, Synchron, Viz.ai , Perflow, and CVAid. Dr. Carvalho de Campos Martins and Dr. Luiz de Melo Bernardi have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Outcomes were mixed among ischemic stroke patients with large vessel occlusion who underwent thrombectomy by an interventional cardiologist as part of a multidisciplinary stroke team, in a single-center, prospective study from Poland.
Results from the 2-year experience show mechanical thrombectomy took longer when carried out by interventional cardiologists than by vascular surgeons and neuroradiologists (120 minutes vs. 105 minutes; P = .020).
The procedures were also less likely to achieve angiographic success, defined as a Thrombolysis in Cerebral Infarction (TICI) scale score of 2b or 3 (55.7% vs. 71.7%; P = .013), reported Krystian Wita, MD, PhD, Medical University of Silesia, Katowice, Poland, and colleagues.
The differences in duration and recanalization require further attention, they noted, and are related to a learning curve, more time dedicated to decision-making and, in some cases, needing a second opinion. Cardiologists performed 80 procedures compared with 116 for vascular surgeons and 52 for neuroradiologists, and treated twice as many patients with a previous stroke (13.9% vs. 6.5%).
Still, the interventional cardiologist- and noncardiologist-treated groups had similar functional independence at 3 months, defined by a modified Rankin Scale (mRS) score of 0 to 2 (44.4% vs. 54.8%; P = .275). Mortality was also similar at 3 months (31.3% vs. 28.0%; P = .595).
“This is the first analysis to prove the noninferiority of the cardiology services in the treatment of stroke with mechanical thrombectomy,” the authors reported in JACC: Cardiovascular Interventions.
But commenting for this news organization, J Mocco, MD, senior vice chair of neurosurgery and director of the Cerebrovascular Center at Mount Sinai Health System, New York, said this study isn’t designed as a noninferiority trial, is “grossly underpowered,” and the comparator cohort is not a gold standard comparator cohort.
“More importantly, they show that the cardiologists got significantly worse technical results and took longer, and we know that technical outcomes and the time to treatment are the two strongest predictors of outcome, which completely correlates with the fact that patients had 11% worse outcomes overall,” he said.
“It’s dumbfounding to me that this has been presented as evidence [that] an interventional cardiologist should be performing thrombectomy,” added Dr. Mocco, president-elect of the Society of NeuroInterventional Surgery.
Dr. Wita and coauthor Andrzej Kulach, MD, PhD, also with the Medical University of Silesia, told this news organization that timing is critical in mechanical thrombectomy (MT) and the sooner it’s performed, the better. But it cannot be performed by just any interventional cardiologist (IC).
“The IC must be trained in the procedure and cooperate with the neurologist to get good results,” they said. “We would like to stress that it is not a procedure for any cath lab and any cardiologist on duty. A network of cardiologists trained in MT must be organized and the stroke teams developed for the local unit to make the strategy reasonable and safe.”
The study was conducted from 2019 to 2020 and to participate, interventional cardiologists had to have performed a minimum of 700 angioplasties and 1,500 coronary angiographies and undergone complex training in thrombectomy, including 14-day training in a reference center and certified courses on a phantom and an animal model. They were also experienced in carotid angioplasty and participated as the second operators in neurointerventions.
“Considering the cardiologists are acting here in a multidisciplinary team led by neurologists, the findings are not surprising,” Dr. Wita and Dr. Kulach said. “What was surprising, is a certain level of skepticism among neurologists when cardiologists are to be involved in the procedure. We hope the quality of cardiology services will help to get over it.”
Major thrombectomy trials such as PRAGUE-16 have supported a role for interventional cardiologists to help meet demand for stroke thrombectomy. Dr. Wita and Dr. Kulach said there’s a lack of trained neuroradiologists and developed infrastructure for thrombectomy, whereas there’s a sufficient network of catheterization laboratories and trained cardiologists who could be involved.
The take-home message from the study, they said, is to “use the existing infrastructure to optimize the treatment of stroke. Building one from the very beginning is more time and resources-consuming.”
Dr. Mocco said a physician’s training is not a factor in the pathway to neurointerventional expertise, as long as they’re willing to put in the appropriate amount of specialization and training.
“There’s no way this represents a turf war or the neurology community somehow protecting its space, which is often used as a distraction, just like the idea that there’s not enough people,” he said. “It’s just not the case. Neurointervention is the most multispecialty space that I’m aware of.”
In the United States, at least, the problem isn’t a lack of resources or people to provide the service, but in getting patients to the correct hospitals, Dr. Mocco said. “We don’t have regionalized stroke care in the United States for the most part, so patients go to any hospital that says they provide stroke care rather than necessarily being triaged to capable centers that can provide the care.”
A 2021 Medicare analysis by Dr. Mocco and colleagues found that higher physician and hospital stroke thrombectomy volumes were associated with lower inpatient mortality and better outcomes.
Efforts are underway to regionalize care and delivery of patients in Los Angeles County and New York City, for example, where ambulances preferentially take patients with suspected large vessel occlusion to thrombectomy-capable stroke centers certified by independent organizations, Dr. Mocco said. In New York, “they’ve shown it has improved outcomes.”
Estêvão Carvalho de Campos Martins, MD, Hospital de Força Aérea do Galeão, Rio de Janeiro, and Fernando Luiz de Melo Bernardi, MD, Hospital Regional do Oeste, Chapecó, Brazil, noted in an accompanying editorial that the observational study is “hypothesis-generating only” and that the disconnect between technical and clinical outcomes is due to a type II error of low power.
They suggest that collaboration between specialties will be “essential for defining the optimal training program, so that ICs can reach solid procedural results.
“The accumulated experience with virtual simulation-based training for stroke could act as an educational accelerator but should be inserted in a prespecified program,” the editorialists said. “How to train and how to insert ICs into [an] MT interdisciplinary team is the current debate; meanwhile ICs are here, and many of them already contributing.”
Dr. Mocco is the principal investigator on research trials funded by Stryker Neurovascular, Microvention, and Penumbra; and is an investor in Cerebrotech, Imperative Care, Endostream, Viseon, BlinkTBI, Myra Medical, Serenity, Vastrax, NTI, RIST, Viz.ai , Synchron, Radical, and Truvic. He serves, or has recently served, as a consultant for: Cerebrotech, Viseon, Endostream, Vastrax, RIST, Synchron, Viz.ai , Perflow, and CVAid. Dr. Carvalho de Campos Martins and Dr. Luiz de Melo Bernardi have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
DOACs comparable to warfarin in CVT
and are less likely to result in major bleeding, a retrospective study suggests.
The ACTION CVT study was presented at the International Stroke Conference (ISC) 2022 by Ekaterina Bakradze, MD, assistant professor of neurology at the University of Alabama at Birmingham.
It was also simultaneously published online in Stroke.
“This real-world data supports use of direct oral anticoagulant drugs as a reasonable alternative to warfarin in patients with cerebral venous thrombosis,” Dr. Bakradze concluded.
But she added that because this study was based on retrospective observational data, the findings should be interpreted with caution and require confirmation by larger prospective studies.
Two such studies are now underway: the Direct Oral Anticoagulants in the Treatment of Cerebral Venous Thrombosis (DOAC-CVT) study and the randomized Study of Rivaroxaban for Cerebral Venous Thrombosis (SECRET) trial.
Dr. Bakradze explained that cerebral venous thrombosis is a less common cause of stroke and occurs more often in women and younger patients, with a median age of 37 years. Current recommended treatment consists of heparin followed by oral anticoagulation.
She noted that although randomized trials and current guidelines indicate that DOACs are a preferred alternative to warfarin for the treatment of patients with venous thromboembolism, there are limited data on their use in patients with CVT.
A small, randomized trial (RESPECT-CVT) showed no significant difference in efficacy and safety outcomes between dabigatran and warfarin in patients with cerebral venous thrombosis, but with only 120 patients, this trial was too small for definite answers to this question.
A better understanding of this issue is important, because the mechanisms underlying cerebral venous thrombosis and other thromboembolism and their subsequent risks may differ, Dr. Bakradze said.
As randomized trials in patients with cerebral venous thrombosis are difficult to perform because the condition has a low incidence and low event rates, the researchers decided to look at this question with a large retrospective multicenter study.
The ACTION-CVT study involved 845 consecutive patients with cerebral venous thrombosis over 6 years (from January 2015 and December 2020) from 27 centers in Italy, New Zealand, Switzerland, and the United States. Patients were identified from medical records with diagnostic codes and confirmed with imaging.
The primary predictor in the study was oral anticoagulant type (DOAC vs. warfarin). Study outcomes were abstracted by individual sites through review of all available medical records.
The primary outcome was recurrent venous thrombosis (venous thromboembolism or cerebral venous thrombosis) during follow-up. Imaging outcomes based on recanalization status on last venous imaging study abstracted from radiology reports were also reported.
The safety outcome was major hemorrhage, defined as new or worsening intracranial hemorrhage (ICH), or major extracranial hemorrhage. Results were adjusted for age, sex, and relevant medical conditions.
The mean age of the patients included was 44.8 years, 64.7% were women, 33% received DOAC only, 51.8% received warfarin only, and 15.1% received both treatments at different times.
Results showed that during a median follow-up of 345 days, there were 5.68 recurrent venous thrombosis events, 3.77 major hemorrhages, and 1.84 deaths per 100 patient-years.
Among 525 patients who met recanalization analysis inclusion criteria, 36.6% had complete, 48.2% had partial, and 15.2% had no recanalization.
When compared with warfarin, DOAC treatment was associated with similar risk for recurrent venous thrombosis (adjusted hazard ratio, 0.94; 95% confidence interval, 0.51-1.73; P = .84), death (aHR, 0.71, 95% CI, 0.24-2.08; P = .53), and rate of partial/complete recanalization (aHR, 0.92, 95% CI, 0.48-1.73; P = .79).
But patients who received a DOAC had a significantly lower rate of major hemorrhage (aHR, 0.35; 95% CI, 0.15-0.81; P = .02).
When examined separately, the occurrence of ICH per 100 patient-years was much lower among the patients prescribed DOACs than those who were prescribed warfarin (1.52 vs. 3.51), whereas the occurrence of major bleeding outside the brain was similar (0.91 vs. 1.15).
Similar efficacy, better safety
Commenting on the study at an ISC press conference, Mitchell Elkind, MD, immediate past president of the American Heart Association/American Stroke Association and professor of neurology at Columbia University, New York, said: “The community has been concerned about extending the use of these new direct-acting oral anticoagulant drugs to cerebral venous thrombosis, but this study suggests that these patients may benefit from these new agents too.”
Tudor Jovin, MD, chair of neurology at Cooper University Hospital, Cherry Hill, New Jersey, also commented: “This study confirms what we already know from other indications about these DOAC drugs: that they have similar efficacy to warfarin but a better safety profile. These results are really spot on with that. These drugs are also much easier and more convenient to use than warfarin.”
“This is a great step forward,” he added. “Only 30% of patients in this study received DOACs, reflecting the fact that clinicians may be a little reluctant to use them in this condition. But this study now has the potential to change practice.”
In an editorial accompanying the publication in Stroke, Johnathon Gorman, MD, and Thalia Field, MD, from the Vancouver Stroke Program at the University of British Columbia, say that despite its methodological limitations, the ACTION-CVT study “provides added value to the current state of knowledge by virtue of its size and ‘real world’ setting that is reflective of how DOACs are being used to manage CVT in current clinical practice.”
They point out that although baseline characteristics between the DOAC and warfarin groups were similar, the possibility of confounding cannot be excluded, and “other characteristics not easily captured in a retrospective study may sway anticoagulation strategy.”
They acknowledge, however, that an additional propensity score analysis “provides reassurance that the groups are reasonably balanced, adjusting for variables associated with recurrent cerebral venous thrombosis, recanalization, and hemorrhage.”
The editorialists conclude that ACTION-CVT gives additional reassurance for DOACs as an alternative approach to warfarin as a treatment for cerebral venous thrombosis and for the shifts in clinical practice that are already occurring at many centers.
The study was partially supported by the Italian Ministry of Health Ricerca Corrente–IRCCS MultiMedica. Dr. Bakradze reports no disclosures. Dr. Field is the principal investigator of the SECRET trial, which received in-kind study medication from Bayer Canada. She reports honoraria from HLS Therapeutics outside the submitted work and is on the board of Destine Health. The other editorialist reports no conflicts.
A version of this article first appeared on Medscape.com.
and are less likely to result in major bleeding, a retrospective study suggests.
The ACTION CVT study was presented at the International Stroke Conference (ISC) 2022 by Ekaterina Bakradze, MD, assistant professor of neurology at the University of Alabama at Birmingham.
It was also simultaneously published online in Stroke.
“This real-world data supports use of direct oral anticoagulant drugs as a reasonable alternative to warfarin in patients with cerebral venous thrombosis,” Dr. Bakradze concluded.
But she added that because this study was based on retrospective observational data, the findings should be interpreted with caution and require confirmation by larger prospective studies.
Two such studies are now underway: the Direct Oral Anticoagulants in the Treatment of Cerebral Venous Thrombosis (DOAC-CVT) study and the randomized Study of Rivaroxaban for Cerebral Venous Thrombosis (SECRET) trial.
Dr. Bakradze explained that cerebral venous thrombosis is a less common cause of stroke and occurs more often in women and younger patients, with a median age of 37 years. Current recommended treatment consists of heparin followed by oral anticoagulation.
She noted that although randomized trials and current guidelines indicate that DOACs are a preferred alternative to warfarin for the treatment of patients with venous thromboembolism, there are limited data on their use in patients with CVT.
A small, randomized trial (RESPECT-CVT) showed no significant difference in efficacy and safety outcomes between dabigatran and warfarin in patients with cerebral venous thrombosis, but with only 120 patients, this trial was too small for definite answers to this question.
A better understanding of this issue is important, because the mechanisms underlying cerebral venous thrombosis and other thromboembolism and their subsequent risks may differ, Dr. Bakradze said.
As randomized trials in patients with cerebral venous thrombosis are difficult to perform because the condition has a low incidence and low event rates, the researchers decided to look at this question with a large retrospective multicenter study.
The ACTION-CVT study involved 845 consecutive patients with cerebral venous thrombosis over 6 years (from January 2015 and December 2020) from 27 centers in Italy, New Zealand, Switzerland, and the United States. Patients were identified from medical records with diagnostic codes and confirmed with imaging.
The primary predictor in the study was oral anticoagulant type (DOAC vs. warfarin). Study outcomes were abstracted by individual sites through review of all available medical records.
The primary outcome was recurrent venous thrombosis (venous thromboembolism or cerebral venous thrombosis) during follow-up. Imaging outcomes based on recanalization status on last venous imaging study abstracted from radiology reports were also reported.
The safety outcome was major hemorrhage, defined as new or worsening intracranial hemorrhage (ICH), or major extracranial hemorrhage. Results were adjusted for age, sex, and relevant medical conditions.
The mean age of the patients included was 44.8 years, 64.7% were women, 33% received DOAC only, 51.8% received warfarin only, and 15.1% received both treatments at different times.
Results showed that during a median follow-up of 345 days, there were 5.68 recurrent venous thrombosis events, 3.77 major hemorrhages, and 1.84 deaths per 100 patient-years.
Among 525 patients who met recanalization analysis inclusion criteria, 36.6% had complete, 48.2% had partial, and 15.2% had no recanalization.
When compared with warfarin, DOAC treatment was associated with similar risk for recurrent venous thrombosis (adjusted hazard ratio, 0.94; 95% confidence interval, 0.51-1.73; P = .84), death (aHR, 0.71, 95% CI, 0.24-2.08; P = .53), and rate of partial/complete recanalization (aHR, 0.92, 95% CI, 0.48-1.73; P = .79).
But patients who received a DOAC had a significantly lower rate of major hemorrhage (aHR, 0.35; 95% CI, 0.15-0.81; P = .02).
When examined separately, the occurrence of ICH per 100 patient-years was much lower among the patients prescribed DOACs than those who were prescribed warfarin (1.52 vs. 3.51), whereas the occurrence of major bleeding outside the brain was similar (0.91 vs. 1.15).
Similar efficacy, better safety
Commenting on the study at an ISC press conference, Mitchell Elkind, MD, immediate past president of the American Heart Association/American Stroke Association and professor of neurology at Columbia University, New York, said: “The community has been concerned about extending the use of these new direct-acting oral anticoagulant drugs to cerebral venous thrombosis, but this study suggests that these patients may benefit from these new agents too.”
Tudor Jovin, MD, chair of neurology at Cooper University Hospital, Cherry Hill, New Jersey, also commented: “This study confirms what we already know from other indications about these DOAC drugs: that they have similar efficacy to warfarin but a better safety profile. These results are really spot on with that. These drugs are also much easier and more convenient to use than warfarin.”
“This is a great step forward,” he added. “Only 30% of patients in this study received DOACs, reflecting the fact that clinicians may be a little reluctant to use them in this condition. But this study now has the potential to change practice.”
In an editorial accompanying the publication in Stroke, Johnathon Gorman, MD, and Thalia Field, MD, from the Vancouver Stroke Program at the University of British Columbia, say that despite its methodological limitations, the ACTION-CVT study “provides added value to the current state of knowledge by virtue of its size and ‘real world’ setting that is reflective of how DOACs are being used to manage CVT in current clinical practice.”
They point out that although baseline characteristics between the DOAC and warfarin groups were similar, the possibility of confounding cannot be excluded, and “other characteristics not easily captured in a retrospective study may sway anticoagulation strategy.”
They acknowledge, however, that an additional propensity score analysis “provides reassurance that the groups are reasonably balanced, adjusting for variables associated with recurrent cerebral venous thrombosis, recanalization, and hemorrhage.”
The editorialists conclude that ACTION-CVT gives additional reassurance for DOACs as an alternative approach to warfarin as a treatment for cerebral venous thrombosis and for the shifts in clinical practice that are already occurring at many centers.
The study was partially supported by the Italian Ministry of Health Ricerca Corrente–IRCCS MultiMedica. Dr. Bakradze reports no disclosures. Dr. Field is the principal investigator of the SECRET trial, which received in-kind study medication from Bayer Canada. She reports honoraria from HLS Therapeutics outside the submitted work and is on the board of Destine Health. The other editorialist reports no conflicts.
A version of this article first appeared on Medscape.com.
and are less likely to result in major bleeding, a retrospective study suggests.
The ACTION CVT study was presented at the International Stroke Conference (ISC) 2022 by Ekaterina Bakradze, MD, assistant professor of neurology at the University of Alabama at Birmingham.
It was also simultaneously published online in Stroke.
“This real-world data supports use of direct oral anticoagulant drugs as a reasonable alternative to warfarin in patients with cerebral venous thrombosis,” Dr. Bakradze concluded.
But she added that because this study was based on retrospective observational data, the findings should be interpreted with caution and require confirmation by larger prospective studies.
Two such studies are now underway: the Direct Oral Anticoagulants in the Treatment of Cerebral Venous Thrombosis (DOAC-CVT) study and the randomized Study of Rivaroxaban for Cerebral Venous Thrombosis (SECRET) trial.
Dr. Bakradze explained that cerebral venous thrombosis is a less common cause of stroke and occurs more often in women and younger patients, with a median age of 37 years. Current recommended treatment consists of heparin followed by oral anticoagulation.
She noted that although randomized trials and current guidelines indicate that DOACs are a preferred alternative to warfarin for the treatment of patients with venous thromboembolism, there are limited data on their use in patients with CVT.
A small, randomized trial (RESPECT-CVT) showed no significant difference in efficacy and safety outcomes between dabigatran and warfarin in patients with cerebral venous thrombosis, but with only 120 patients, this trial was too small for definite answers to this question.
A better understanding of this issue is important, because the mechanisms underlying cerebral venous thrombosis and other thromboembolism and their subsequent risks may differ, Dr. Bakradze said.
As randomized trials in patients with cerebral venous thrombosis are difficult to perform because the condition has a low incidence and low event rates, the researchers decided to look at this question with a large retrospective multicenter study.
The ACTION-CVT study involved 845 consecutive patients with cerebral venous thrombosis over 6 years (from January 2015 and December 2020) from 27 centers in Italy, New Zealand, Switzerland, and the United States. Patients were identified from medical records with diagnostic codes and confirmed with imaging.
The primary predictor in the study was oral anticoagulant type (DOAC vs. warfarin). Study outcomes were abstracted by individual sites through review of all available medical records.
The primary outcome was recurrent venous thrombosis (venous thromboembolism or cerebral venous thrombosis) during follow-up. Imaging outcomes based on recanalization status on last venous imaging study abstracted from radiology reports were also reported.
The safety outcome was major hemorrhage, defined as new or worsening intracranial hemorrhage (ICH), or major extracranial hemorrhage. Results were adjusted for age, sex, and relevant medical conditions.
The mean age of the patients included was 44.8 years, 64.7% were women, 33% received DOAC only, 51.8% received warfarin only, and 15.1% received both treatments at different times.
Results showed that during a median follow-up of 345 days, there were 5.68 recurrent venous thrombosis events, 3.77 major hemorrhages, and 1.84 deaths per 100 patient-years.
Among 525 patients who met recanalization analysis inclusion criteria, 36.6% had complete, 48.2% had partial, and 15.2% had no recanalization.
When compared with warfarin, DOAC treatment was associated with similar risk for recurrent venous thrombosis (adjusted hazard ratio, 0.94; 95% confidence interval, 0.51-1.73; P = .84), death (aHR, 0.71, 95% CI, 0.24-2.08; P = .53), and rate of partial/complete recanalization (aHR, 0.92, 95% CI, 0.48-1.73; P = .79).
But patients who received a DOAC had a significantly lower rate of major hemorrhage (aHR, 0.35; 95% CI, 0.15-0.81; P = .02).
When examined separately, the occurrence of ICH per 100 patient-years was much lower among the patients prescribed DOACs than those who were prescribed warfarin (1.52 vs. 3.51), whereas the occurrence of major bleeding outside the brain was similar (0.91 vs. 1.15).
Similar efficacy, better safety
Commenting on the study at an ISC press conference, Mitchell Elkind, MD, immediate past president of the American Heart Association/American Stroke Association and professor of neurology at Columbia University, New York, said: “The community has been concerned about extending the use of these new direct-acting oral anticoagulant drugs to cerebral venous thrombosis, but this study suggests that these patients may benefit from these new agents too.”
Tudor Jovin, MD, chair of neurology at Cooper University Hospital, Cherry Hill, New Jersey, also commented: “This study confirms what we already know from other indications about these DOAC drugs: that they have similar efficacy to warfarin but a better safety profile. These results are really spot on with that. These drugs are also much easier and more convenient to use than warfarin.”
“This is a great step forward,” he added. “Only 30% of patients in this study received DOACs, reflecting the fact that clinicians may be a little reluctant to use them in this condition. But this study now has the potential to change practice.”
In an editorial accompanying the publication in Stroke, Johnathon Gorman, MD, and Thalia Field, MD, from the Vancouver Stroke Program at the University of British Columbia, say that despite its methodological limitations, the ACTION-CVT study “provides added value to the current state of knowledge by virtue of its size and ‘real world’ setting that is reflective of how DOACs are being used to manage CVT in current clinical practice.”
They point out that although baseline characteristics between the DOAC and warfarin groups were similar, the possibility of confounding cannot be excluded, and “other characteristics not easily captured in a retrospective study may sway anticoagulation strategy.”
They acknowledge, however, that an additional propensity score analysis “provides reassurance that the groups are reasonably balanced, adjusting for variables associated with recurrent cerebral venous thrombosis, recanalization, and hemorrhage.”
The editorialists conclude that ACTION-CVT gives additional reassurance for DOACs as an alternative approach to warfarin as a treatment for cerebral venous thrombosis and for the shifts in clinical practice that are already occurring at many centers.
The study was partially supported by the Italian Ministry of Health Ricerca Corrente–IRCCS MultiMedica. Dr. Bakradze reports no disclosures. Dr. Field is the principal investigator of the SECRET trial, which received in-kind study medication from Bayer Canada. She reports honoraria from HLS Therapeutics outside the submitted work and is on the board of Destine Health. The other editorialist reports no conflicts.
A version of this article first appeared on Medscape.com.
From ISC 2022
Stroke risk is highest right after COVID infection
, new research shows.
The study among Medicare beneficiaries with COVID-19 also showed that stroke risk is higher for relatively young older adults, those aged 65 to 74 years, and those without a history of stroke.
The study highlights the impact COVID-19 has on the cardiovascular system, said study author Quanhe Yang, PhD, senior scientist, Division for Heart Disease and Stroke Prevention, Centers for Disease Control and Prevention, Atlanta.
“Clinicians and patients should understand that stroke might be one of the very important clinical consequences of COVID-19.”
The study was presented during the hybrid International Stroke Conference held in New Orleans and online. The meeting was presented by the American Stroke Association, a division of the American Heart Association.
Stroke is the fifth leading cause of death in the U.S. As an increasing number of people become infected with COVID-19, “it’s important to determine if there’s a relationship between COVID and the risk of stroke,” said Dr. Yang.
Findings from prior research examining the link between stroke and COVID-19 have been inconsistent, he noted. Some studies found an association while others did not, and in still others, the association was not as strong as expected.
Many factors may contribute to these inconsistent findings, said Dr. Yang, including differences in study design, inclusion criteria, comparison groups, sample sizes, and countries where the research was carried out. Dr. Yang pointed out that many of these studies were done in the early stages of the pandemic or didn’t include older adults, the population most at risk for stroke.
The current study included 19,553 Medicare beneficiaries aged 65 years and older diagnosed with COVID-19 and hospitalized with acute ischemic stroke. The median age at diagnosis of COVID-19 was 80.5 years, 57.5% were women, and more than 75% were non-Hispanic Whites.
To ensure the stroke occurred after a COVID infection, researchers used a self-controlled case series study design, a “within person” comparison between the risk period and the control period.
They divided the study period (Jan. 1, 2019 to Feb. 28, 2021) into the exposure or stroke risk periods after the COVID diagnosis (0-3 days; 4-7 days; 8-15 days; and 15-28 days) and control periods.
Strokes that occurred 7 days before or 28 days after a COVID diagnosis served as a control period. “Any stroke that occurred outside the risk window is in the control period,” explained Dr. Yang.
He added that the control period provides a baseline. “Without COVID-19, this is what I would expect” in terms of the number of strokes.
To estimate the incidence rate ratio (IRR), investigators compared the incidence of acute ischemic stroke in the various risk periods with control periods.
The IRR was 10.97 (95% confidence interval, 10.30-11.68) at 0-3 days. The risk then quickly declined but stayed higher than the control period. The IRRs were: 1.59 (95% CI, 1.35-1.87) at 4-7 days; 1.23 (95% CI, 1.07-1.41) at 8-14 days; and 1.06 (95% CI, 0.95-1.18) at 15-28 days.
The temporary increase in stroke risk early after an infection isn’t novel; the pattern has been observed with influenza, respiratory infections, and shingles, said Dr. Yang. “But COVID-19 appears to be particularly risky.”
Although the mechanism driving the early increased stroke risk isn’t fully understood, it’s likely tied to an “exaggerated inflammatory response,” said Dr. Yang. This can trigger the cascade of events setting the stage for a stroke – a hypercoagulation state leading to the formation of blood clots that then block arteries to the brain, he said.
It’s also possible the infection directly affects endothelial cells, leading to rupture of plaque, again blocking arteries and raising stroke risks, added Dr. Yang.
The association was stronger among younger beneficiaries, aged 65 to 74 years, compared with those 85 years and older, a finding Dr. Yang said was somewhat surprising. But he noted other studies have found stroke patients with COVID are younger than stroke patients without COVID – by some 5 to 6 years.
“If COVID-19 disproportionately affects younger patients, that may explain the stronger association,” said Dr. Yang. “Stroke risk increases tremendously with age, so if you’re a younger age, your baseline stroke risk is lower.”
The association was also stronger among beneficiaries without a history of stroke. Again, this could be related to the stronger association among younger patients who are less likely to have suffered a stroke. The association was largely consistent across sex and race/ethnicities.
Dr. Yang stressed that the findings need to be confirmed with further studies.
The study was carried out before widespread use of vaccinations in the U.S. Once those data are available, Dr. Yang and his colleagues plan to determine if vaccinations modify the association between COVID-19 and stroke risk.
The new results contribute to the mounting evidence that a COVID-19 infection “can actually affect multiple human organs structurally or functionally in addition to the impact on [the] respiratory system,” said Dr. Yang.
Some dates of COVID-19 diagnoses may be incorrect due to limited test availability, particularly early in the pandemic. Another limitation of the study was possible misclassification from the use of Medicare real-time preliminary claims.
In a provided statement, Louise D. McCullough, MD, PhD, chair of the ISC 2022 and professor and chair of neurology, McGovern Medical School, University of Texas Health Science Center at Houston, noted that the study focused on older adults because it was examining Medicare beneficiaries.
“But everyone is likely at risk for stroke after COVID,” she said. “Any infection is linked to stroke risk, probably because any infection will cause inflammation, and inflammation can cause clots or thrombus, which is the cause of stroke.”
There was no outside funding for the study. No relevant conflicts of interest were disclosed.
A version of this article first appeared on Medscape.com.
, new research shows.
The study among Medicare beneficiaries with COVID-19 also showed that stroke risk is higher for relatively young older adults, those aged 65 to 74 years, and those without a history of stroke.
The study highlights the impact COVID-19 has on the cardiovascular system, said study author Quanhe Yang, PhD, senior scientist, Division for Heart Disease and Stroke Prevention, Centers for Disease Control and Prevention, Atlanta.
“Clinicians and patients should understand that stroke might be one of the very important clinical consequences of COVID-19.”
The study was presented during the hybrid International Stroke Conference held in New Orleans and online. The meeting was presented by the American Stroke Association, a division of the American Heart Association.
Stroke is the fifth leading cause of death in the U.S. As an increasing number of people become infected with COVID-19, “it’s important to determine if there’s a relationship between COVID and the risk of stroke,” said Dr. Yang.
Findings from prior research examining the link between stroke and COVID-19 have been inconsistent, he noted. Some studies found an association while others did not, and in still others, the association was not as strong as expected.
Many factors may contribute to these inconsistent findings, said Dr. Yang, including differences in study design, inclusion criteria, comparison groups, sample sizes, and countries where the research was carried out. Dr. Yang pointed out that many of these studies were done in the early stages of the pandemic or didn’t include older adults, the population most at risk for stroke.
The current study included 19,553 Medicare beneficiaries aged 65 years and older diagnosed with COVID-19 and hospitalized with acute ischemic stroke. The median age at diagnosis of COVID-19 was 80.5 years, 57.5% were women, and more than 75% were non-Hispanic Whites.
To ensure the stroke occurred after a COVID infection, researchers used a self-controlled case series study design, a “within person” comparison between the risk period and the control period.
They divided the study period (Jan. 1, 2019 to Feb. 28, 2021) into the exposure or stroke risk periods after the COVID diagnosis (0-3 days; 4-7 days; 8-15 days; and 15-28 days) and control periods.
Strokes that occurred 7 days before or 28 days after a COVID diagnosis served as a control period. “Any stroke that occurred outside the risk window is in the control period,” explained Dr. Yang.
He added that the control period provides a baseline. “Without COVID-19, this is what I would expect” in terms of the number of strokes.
To estimate the incidence rate ratio (IRR), investigators compared the incidence of acute ischemic stroke in the various risk periods with control periods.
The IRR was 10.97 (95% confidence interval, 10.30-11.68) at 0-3 days. The risk then quickly declined but stayed higher than the control period. The IRRs were: 1.59 (95% CI, 1.35-1.87) at 4-7 days; 1.23 (95% CI, 1.07-1.41) at 8-14 days; and 1.06 (95% CI, 0.95-1.18) at 15-28 days.
The temporary increase in stroke risk early after an infection isn’t novel; the pattern has been observed with influenza, respiratory infections, and shingles, said Dr. Yang. “But COVID-19 appears to be particularly risky.”
Although the mechanism driving the early increased stroke risk isn’t fully understood, it’s likely tied to an “exaggerated inflammatory response,” said Dr. Yang. This can trigger the cascade of events setting the stage for a stroke – a hypercoagulation state leading to the formation of blood clots that then block arteries to the brain, he said.
It’s also possible the infection directly affects endothelial cells, leading to rupture of plaque, again blocking arteries and raising stroke risks, added Dr. Yang.
The association was stronger among younger beneficiaries, aged 65 to 74 years, compared with those 85 years and older, a finding Dr. Yang said was somewhat surprising. But he noted other studies have found stroke patients with COVID are younger than stroke patients without COVID – by some 5 to 6 years.
“If COVID-19 disproportionately affects younger patients, that may explain the stronger association,” said Dr. Yang. “Stroke risk increases tremendously with age, so if you’re a younger age, your baseline stroke risk is lower.”
The association was also stronger among beneficiaries without a history of stroke. Again, this could be related to the stronger association among younger patients who are less likely to have suffered a stroke. The association was largely consistent across sex and race/ethnicities.
Dr. Yang stressed that the findings need to be confirmed with further studies.
The study was carried out before widespread use of vaccinations in the U.S. Once those data are available, Dr. Yang and his colleagues plan to determine if vaccinations modify the association between COVID-19 and stroke risk.
The new results contribute to the mounting evidence that a COVID-19 infection “can actually affect multiple human organs structurally or functionally in addition to the impact on [the] respiratory system,” said Dr. Yang.
Some dates of COVID-19 diagnoses may be incorrect due to limited test availability, particularly early in the pandemic. Another limitation of the study was possible misclassification from the use of Medicare real-time preliminary claims.
In a provided statement, Louise D. McCullough, MD, PhD, chair of the ISC 2022 and professor and chair of neurology, McGovern Medical School, University of Texas Health Science Center at Houston, noted that the study focused on older adults because it was examining Medicare beneficiaries.
“But everyone is likely at risk for stroke after COVID,” she said. “Any infection is linked to stroke risk, probably because any infection will cause inflammation, and inflammation can cause clots or thrombus, which is the cause of stroke.”
There was no outside funding for the study. No relevant conflicts of interest were disclosed.
A version of this article first appeared on Medscape.com.
, new research shows.
The study among Medicare beneficiaries with COVID-19 also showed that stroke risk is higher for relatively young older adults, those aged 65 to 74 years, and those without a history of stroke.
The study highlights the impact COVID-19 has on the cardiovascular system, said study author Quanhe Yang, PhD, senior scientist, Division for Heart Disease and Stroke Prevention, Centers for Disease Control and Prevention, Atlanta.
“Clinicians and patients should understand that stroke might be one of the very important clinical consequences of COVID-19.”
The study was presented during the hybrid International Stroke Conference held in New Orleans and online. The meeting was presented by the American Stroke Association, a division of the American Heart Association.
Stroke is the fifth leading cause of death in the U.S. As an increasing number of people become infected with COVID-19, “it’s important to determine if there’s a relationship between COVID and the risk of stroke,” said Dr. Yang.
Findings from prior research examining the link between stroke and COVID-19 have been inconsistent, he noted. Some studies found an association while others did not, and in still others, the association was not as strong as expected.
Many factors may contribute to these inconsistent findings, said Dr. Yang, including differences in study design, inclusion criteria, comparison groups, sample sizes, and countries where the research was carried out. Dr. Yang pointed out that many of these studies were done in the early stages of the pandemic or didn’t include older adults, the population most at risk for stroke.
The current study included 19,553 Medicare beneficiaries aged 65 years and older diagnosed with COVID-19 and hospitalized with acute ischemic stroke. The median age at diagnosis of COVID-19 was 80.5 years, 57.5% were women, and more than 75% were non-Hispanic Whites.
To ensure the stroke occurred after a COVID infection, researchers used a self-controlled case series study design, a “within person” comparison between the risk period and the control period.
They divided the study period (Jan. 1, 2019 to Feb. 28, 2021) into the exposure or stroke risk periods after the COVID diagnosis (0-3 days; 4-7 days; 8-15 days; and 15-28 days) and control periods.
Strokes that occurred 7 days before or 28 days after a COVID diagnosis served as a control period. “Any stroke that occurred outside the risk window is in the control period,” explained Dr. Yang.
He added that the control period provides a baseline. “Without COVID-19, this is what I would expect” in terms of the number of strokes.
To estimate the incidence rate ratio (IRR), investigators compared the incidence of acute ischemic stroke in the various risk periods with control periods.
The IRR was 10.97 (95% confidence interval, 10.30-11.68) at 0-3 days. The risk then quickly declined but stayed higher than the control period. The IRRs were: 1.59 (95% CI, 1.35-1.87) at 4-7 days; 1.23 (95% CI, 1.07-1.41) at 8-14 days; and 1.06 (95% CI, 0.95-1.18) at 15-28 days.
The temporary increase in stroke risk early after an infection isn’t novel; the pattern has been observed with influenza, respiratory infections, and shingles, said Dr. Yang. “But COVID-19 appears to be particularly risky.”
Although the mechanism driving the early increased stroke risk isn’t fully understood, it’s likely tied to an “exaggerated inflammatory response,” said Dr. Yang. This can trigger the cascade of events setting the stage for a stroke – a hypercoagulation state leading to the formation of blood clots that then block arteries to the brain, he said.
It’s also possible the infection directly affects endothelial cells, leading to rupture of plaque, again blocking arteries and raising stroke risks, added Dr. Yang.
The association was stronger among younger beneficiaries, aged 65 to 74 years, compared with those 85 years and older, a finding Dr. Yang said was somewhat surprising. But he noted other studies have found stroke patients with COVID are younger than stroke patients without COVID – by some 5 to 6 years.
“If COVID-19 disproportionately affects younger patients, that may explain the stronger association,” said Dr. Yang. “Stroke risk increases tremendously with age, so if you’re a younger age, your baseline stroke risk is lower.”
The association was also stronger among beneficiaries without a history of stroke. Again, this could be related to the stronger association among younger patients who are less likely to have suffered a stroke. The association was largely consistent across sex and race/ethnicities.
Dr. Yang stressed that the findings need to be confirmed with further studies.
The study was carried out before widespread use of vaccinations in the U.S. Once those data are available, Dr. Yang and his colleagues plan to determine if vaccinations modify the association between COVID-19 and stroke risk.
The new results contribute to the mounting evidence that a COVID-19 infection “can actually affect multiple human organs structurally or functionally in addition to the impact on [the] respiratory system,” said Dr. Yang.
Some dates of COVID-19 diagnoses may be incorrect due to limited test availability, particularly early in the pandemic. Another limitation of the study was possible misclassification from the use of Medicare real-time preliminary claims.
In a provided statement, Louise D. McCullough, MD, PhD, chair of the ISC 2022 and professor and chair of neurology, McGovern Medical School, University of Texas Health Science Center at Houston, noted that the study focused on older adults because it was examining Medicare beneficiaries.
“But everyone is likely at risk for stroke after COVID,” she said. “Any infection is linked to stroke risk, probably because any infection will cause inflammation, and inflammation can cause clots or thrombus, which is the cause of stroke.”
There was no outside funding for the study. No relevant conflicts of interest were disclosed.
A version of this article first appeared on Medscape.com.
FROM ISC 2022
AHA statement reviews marijuana’s effects on brain health
Medicinal and recreational marijuana use has become common across the country, warranting greater awareness among clinicians about any potential adverse effects of marijuana on brain health, a new American Heart Association scientific statement concludes.
although the specific adverse effects have not been well defined, the statement authors said.
Fernando D. Testai, MD, PhD, professor of neurology and rehabilitation at the University of Illinois at Chicago, led the writing panel for the statement, published online Feb. 10, 2022, in Stroke.
Numerous research studies challenge the idea that marijuana use is harmless, and instead demonstrate that cannabis, especially tetrahydrocannabinol (THC), has adverse effects on brain health, Dr. Testai and colleagues noted.
“Social media tends to overemphasize the beneficial effects of marijuana. However, its ultimate effect on brain health is still to be established. Physicians should provide periodic and unbiased education to their patients about the known and unknown ramifications of consuming cannabinoids,” Dr. Testai said.
Findings collected from animal studies demonstrate that THC interferes with normal development of signaling pathways and hinders synaptic plasticity. The authors also pointed out that these studies show connections between neurons are affected in the short term, whereas in the long haul, this contributes to changes in how neuronal networks work.
“Personally, the most striking point is the epidemiological data that indicate that the use of marijuana is widespread in the general population, and this starts early in life, particularly during adolescence,” Dr. Testai told this news organization.
Dr. Testai also noted that pregnant women are using cannabis for nausea and vomiting. Other data on prenatal exposure to cannabis show that THC hinders the signaling mechanism of the endocannabinoid system during development and ontogenesis, which ultimately leads to abnormal neurotransmission.
“Prenatal THC affects neuroanatomic areas associated with cognition and emotional regulation, including the prefrontal cortex, limbic system, and ventral tegmentum of the midbrain,” the researchers added.
The writing panel also found that marijuana use had effects on human cognition:
- Acute marijuana use affects impulsivity, memory, and behavioral disinhibition, they noted, that “can affect performance in real-world activities,” such as driving. The long-term effects of cannabis on cognition are “less well established.”
- Neuroimaging research has highlighted structural changes in the brain, but these data are inconsistent.
- Functional MRI studies show cannabis users may experience functional changes in regions of the brain that play a role in cognition, particularly with prolonged use.
The statement also addresses studies assessing the effects of marijuana use on cerebrovascular risk and disease, which show:
- A relation between cannabis use and increased risk for stroke.
- Frequency and other trends of cannabis use may raise stroke risk.
- Cannabis users often smoke cigarettes, which is an important factor in the association between cannabis use and stroke risk.
Looking ahead, public health initiatives are needed to increase awareness among the public about the negative effects of marijuana use. Other efforts may include setting standards regarding the concentrations of biologically active ingredients and warning notices on available formulations, the group concluded.
The document was prepared on behalf of the AHA Stroke Brain Health Science Subcommittee of the Stroke Council; Council on Arteriosclerosis, Thrombosis, and Vascular Biology; Council on Cardiovascular and Stroke Nursing; Council on Lifestyle and Cardiometabolic Health; and Council on Peripheral Vascular Disease.
The American Academy of Neurology “affirms the value of this statement as an educational tool for neurologists,” the document notes.
Dr. Testai reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Medicinal and recreational marijuana use has become common across the country, warranting greater awareness among clinicians about any potential adverse effects of marijuana on brain health, a new American Heart Association scientific statement concludes.
although the specific adverse effects have not been well defined, the statement authors said.
Fernando D. Testai, MD, PhD, professor of neurology and rehabilitation at the University of Illinois at Chicago, led the writing panel for the statement, published online Feb. 10, 2022, in Stroke.
Numerous research studies challenge the idea that marijuana use is harmless, and instead demonstrate that cannabis, especially tetrahydrocannabinol (THC), has adverse effects on brain health, Dr. Testai and colleagues noted.
“Social media tends to overemphasize the beneficial effects of marijuana. However, its ultimate effect on brain health is still to be established. Physicians should provide periodic and unbiased education to their patients about the known and unknown ramifications of consuming cannabinoids,” Dr. Testai said.
Findings collected from animal studies demonstrate that THC interferes with normal development of signaling pathways and hinders synaptic plasticity. The authors also pointed out that these studies show connections between neurons are affected in the short term, whereas in the long haul, this contributes to changes in how neuronal networks work.
“Personally, the most striking point is the epidemiological data that indicate that the use of marijuana is widespread in the general population, and this starts early in life, particularly during adolescence,” Dr. Testai told this news organization.
Dr. Testai also noted that pregnant women are using cannabis for nausea and vomiting. Other data on prenatal exposure to cannabis show that THC hinders the signaling mechanism of the endocannabinoid system during development and ontogenesis, which ultimately leads to abnormal neurotransmission.
“Prenatal THC affects neuroanatomic areas associated with cognition and emotional regulation, including the prefrontal cortex, limbic system, and ventral tegmentum of the midbrain,” the researchers added.
The writing panel also found that marijuana use had effects on human cognition:
- Acute marijuana use affects impulsivity, memory, and behavioral disinhibition, they noted, that “can affect performance in real-world activities,” such as driving. The long-term effects of cannabis on cognition are “less well established.”
- Neuroimaging research has highlighted structural changes in the brain, but these data are inconsistent.
- Functional MRI studies show cannabis users may experience functional changes in regions of the brain that play a role in cognition, particularly with prolonged use.
The statement also addresses studies assessing the effects of marijuana use on cerebrovascular risk and disease, which show:
- A relation between cannabis use and increased risk for stroke.
- Frequency and other trends of cannabis use may raise stroke risk.
- Cannabis users often smoke cigarettes, which is an important factor in the association between cannabis use and stroke risk.
Looking ahead, public health initiatives are needed to increase awareness among the public about the negative effects of marijuana use. Other efforts may include setting standards regarding the concentrations of biologically active ingredients and warning notices on available formulations, the group concluded.
The document was prepared on behalf of the AHA Stroke Brain Health Science Subcommittee of the Stroke Council; Council on Arteriosclerosis, Thrombosis, and Vascular Biology; Council on Cardiovascular and Stroke Nursing; Council on Lifestyle and Cardiometabolic Health; and Council on Peripheral Vascular Disease.
The American Academy of Neurology “affirms the value of this statement as an educational tool for neurologists,” the document notes.
Dr. Testai reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Medicinal and recreational marijuana use has become common across the country, warranting greater awareness among clinicians about any potential adverse effects of marijuana on brain health, a new American Heart Association scientific statement concludes.
although the specific adverse effects have not been well defined, the statement authors said.
Fernando D. Testai, MD, PhD, professor of neurology and rehabilitation at the University of Illinois at Chicago, led the writing panel for the statement, published online Feb. 10, 2022, in Stroke.
Numerous research studies challenge the idea that marijuana use is harmless, and instead demonstrate that cannabis, especially tetrahydrocannabinol (THC), has adverse effects on brain health, Dr. Testai and colleagues noted.
“Social media tends to overemphasize the beneficial effects of marijuana. However, its ultimate effect on brain health is still to be established. Physicians should provide periodic and unbiased education to their patients about the known and unknown ramifications of consuming cannabinoids,” Dr. Testai said.
Findings collected from animal studies demonstrate that THC interferes with normal development of signaling pathways and hinders synaptic plasticity. The authors also pointed out that these studies show connections between neurons are affected in the short term, whereas in the long haul, this contributes to changes in how neuronal networks work.
“Personally, the most striking point is the epidemiological data that indicate that the use of marijuana is widespread in the general population, and this starts early in life, particularly during adolescence,” Dr. Testai told this news organization.
Dr. Testai also noted that pregnant women are using cannabis for nausea and vomiting. Other data on prenatal exposure to cannabis show that THC hinders the signaling mechanism of the endocannabinoid system during development and ontogenesis, which ultimately leads to abnormal neurotransmission.
“Prenatal THC affects neuroanatomic areas associated with cognition and emotional regulation, including the prefrontal cortex, limbic system, and ventral tegmentum of the midbrain,” the researchers added.
The writing panel also found that marijuana use had effects on human cognition:
- Acute marijuana use affects impulsivity, memory, and behavioral disinhibition, they noted, that “can affect performance in real-world activities,” such as driving. The long-term effects of cannabis on cognition are “less well established.”
- Neuroimaging research has highlighted structural changes in the brain, but these data are inconsistent.
- Functional MRI studies show cannabis users may experience functional changes in regions of the brain that play a role in cognition, particularly with prolonged use.
The statement also addresses studies assessing the effects of marijuana use on cerebrovascular risk and disease, which show:
- A relation between cannabis use and increased risk for stroke.
- Frequency and other trends of cannabis use may raise stroke risk.
- Cannabis users often smoke cigarettes, which is an important factor in the association between cannabis use and stroke risk.
Looking ahead, public health initiatives are needed to increase awareness among the public about the negative effects of marijuana use. Other efforts may include setting standards regarding the concentrations of biologically active ingredients and warning notices on available formulations, the group concluded.
The document was prepared on behalf of the AHA Stroke Brain Health Science Subcommittee of the Stroke Council; Council on Arteriosclerosis, Thrombosis, and Vascular Biology; Council on Cardiovascular and Stroke Nursing; Council on Lifestyle and Cardiometabolic Health; and Council on Peripheral Vascular Disease.
The American Academy of Neurology “affirms the value of this statement as an educational tool for neurologists,” the document notes.
Dr. Testai reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM STROKE
Can periodontal treatment reduce cardiovascular events in stroke patients?
The first randomized trial to investigate whether periodontal treatment can reduce future risk of cardiovascular events or stroke suggests some promise with this strategy.
The PREMIERS study, which was conducted in patients with a recent stroke or transient ischemic attack (TIA) who also had gum disease, did not show a statistically significant difference between intensive periodontal treatment and standard treatment in the rate of recurrent stroke, myocardial infarction (MI), or death in the 1-year follow-up, although there was a strong trend toward benefit in the intensive group.
Both groups had a much lower event rate compared with a historical control group made up of similar patients.
In addition, the number of dental visits significantly correlated with a reduction in the composite event rate in the study.
“My take-home message from this study is that periodontal treatment does appear to impact cardiovascular outcomes in stroke/TIA patients,” said lead author Souvik Sen, MD, MPH, professor of neurology at the University of South Carolina School of Medicine.
“Even standard periodontal care – a dental cleaning every 3 months – was beneficial.”
Dr. Sen presented the study at the hybrid International Stroke Conference (ISC), taking place in New Orleans and virtually.
“This was a very ambitious study, and it turned out to be very underpowered for the comparisons involved, but I was impressed that we saw such a strong trend toward benefit in the intensive group,” he said at the meeting, presented by the American Stroke Association, a division of the American Heart Association.
Dr. Sen explained that they initially set out to compare periodontal treatment with no treatment, but they were unable to have a control group who received no treatment for ethical reasons, so they ended up comparing standard treatment with intensive treatment.
“We probably needed a study of twice the size for that comparison. But our results are encouraging, and we now plan to do a larger study,” he said.
Dr. Sen reported that gum disease (periodontitis) is extremely prevalent, occurring in around half the U.S. population. It is particularly prevalent in the southeastern part of the United States, known as the “Stroke Belt” because of a much higher incidence of stroke compared with the rest of the country. Gum disease is known to be associated with an increased risk of cardiovascular events and stroke.
For the study, 280 patients from the Stroke Belt area with a recent stroke or TIA and periodontal disease were randomly assigned to standard periodontal treatment or intensive periodontal treatment and followed for 1 year.
Standard treatment was composed of regular (every 3 months) supragingival removal of plaque and calculus; patients were also given a regular toothbrush and advice about dental care.
The intensive group received supragingival and subgingival removal of plaque and calculus (also every 3 months), extraction of hopeless teeth, locally delivered antibiotics. In addition, patients were given an electric toothbrush, mouthwash, and an air flosser for dental care.
All patients received comprehensive conventional stroke risk factor treatment.
The study had an adaptive randomization design to ensure both groups were balanced in terms of age, stroke causes, race, socioeconomic status, and stroke risk factors.
Results showed that after 1 year of follow-up, the primary outcome (stroke/myocardial infarction/death) had occurred in 7.7% of the intensive treatment group versus 12.3% of the standard care group, giving a hazard ratio of 0.65 (95% confidence interval, 0.30-1.38; P = .26).
But both groups had a much lower rate of recurrent events, compared with a historical control group which showed a 1-year rate of stroke/MI/death of 24%. The historical controls were part of an observational study that the same group of researchers conducted previously in a similar population.
In both standard treatment and intensive treatment groups, the combined number of dental visits strongly correlated with a reduction in cardiovascular events. Of the study participants, 65% attended all five visits, 25% attended two to four, and 10% did not attend any after the baseline assessment.
Those who attended all visits in the year had a rate of stroke/MI/death at 1 year of 8%. And those who did not attend any further visits after the baseline visit had an event rate of 25% at 1-year follow-up, which Dr. Sen noted was very similar to that of the historical controls. The P value for this trend was “very significant” (P = .0017), he said.
Secondary outcomes showed a reduction in blood pressure, A1c levels, carotid intima-media thickness, and better lipid profiles in all patients who underwent treatment – in both standard treatment and intensive treatment.
A new part of routine post-stroke care?
“Previous data on how gum disease and periodontal treatment relates to cardiovascular outcomes have all come from observational studies. They have shown that regular dental care is associated with reduced incidence of future cardiovascular events. But until now, we haven’t had any randomized data,” Dr. Sen noted.
He believes advice on oral and dental care should be part of routine clinical practice for patients who have suffered stroke. “This is not something we currently think about, but it could make a big difference in future event rates.”
Dr. Sen said the current study had raised interest in the topic, and his presentation was received with enthusiasm from the audience.
“We are in South Carolina in the Stroke Belt. Previous studies have shown that gum disease is very prevalent in this area. People in this area have a high risk of stroke, but we don’t know all the attributable risk factors. The traditional stroke risk factors do not seem to account for all the excess risk,” Dr. Sen said. “Periodontal disease could be one of the additional risk factors that accounts for the increased stroke risk in this population.”
“I believe doctors treating stroke patients should advise that they pay particular attention to oral care and visit the dentist frequently for periodontal treatment if they have gum disease. It is very unusual for people to get regular dental cleaning. They don’t understand that they need to do this,” he said.
But he acknowledges that larger studies are needed to show statistically significant results to be able to achieve a strong recommendation in the secondary prevention clinical guidelines.
“Even in individuals who haven’t had a stroke or cardiovascular event, population-based observational studies clearly show that gum infection is linked to future risk of myocardial infarction and stroke and that regular dental care (one or more visits per year) can reduce this risk. I don’t think we can do a randomized trial in the general population – that would need enormous numbers. We will have to rely on the observational studies here,” he added.
‘Promising’ results
Commenting on the current study, Louise McCullough, MD, ISC 2022 program chair, said she thought the results were promising.
“There was no difference in the intensive cleaning group versus standard cleaning, but the number of events was small, so it was underpowered to see differences. I think the main take home point is that both groups that came for dental visits had a much lower risk of another event than the group that did not show up for follow-up,” said Dr. McCullough, chair of the department of neurology, McGovern Medical School, University of Texas Health Science Center, Houston. “Clearly, seeing a provider made a difference. It is likely that contact with a dentist, getting blood pressure checked, etc., made a dramatic difference.”
The study was funded by the National Institute of Minority Health Disparity, Phillips Oral Healthcare, and Orapharma (which provided the study antibiotic medication).
A version of this article first appeared on Medscape.com.
The first randomized trial to investigate whether periodontal treatment can reduce future risk of cardiovascular events or stroke suggests some promise with this strategy.
The PREMIERS study, which was conducted in patients with a recent stroke or transient ischemic attack (TIA) who also had gum disease, did not show a statistically significant difference between intensive periodontal treatment and standard treatment in the rate of recurrent stroke, myocardial infarction (MI), or death in the 1-year follow-up, although there was a strong trend toward benefit in the intensive group.
Both groups had a much lower event rate compared with a historical control group made up of similar patients.
In addition, the number of dental visits significantly correlated with a reduction in the composite event rate in the study.
“My take-home message from this study is that periodontal treatment does appear to impact cardiovascular outcomes in stroke/TIA patients,” said lead author Souvik Sen, MD, MPH, professor of neurology at the University of South Carolina School of Medicine.
“Even standard periodontal care – a dental cleaning every 3 months – was beneficial.”
Dr. Sen presented the study at the hybrid International Stroke Conference (ISC), taking place in New Orleans and virtually.
“This was a very ambitious study, and it turned out to be very underpowered for the comparisons involved, but I was impressed that we saw such a strong trend toward benefit in the intensive group,” he said at the meeting, presented by the American Stroke Association, a division of the American Heart Association.
Dr. Sen explained that they initially set out to compare periodontal treatment with no treatment, but they were unable to have a control group who received no treatment for ethical reasons, so they ended up comparing standard treatment with intensive treatment.
“We probably needed a study of twice the size for that comparison. But our results are encouraging, and we now plan to do a larger study,” he said.
Dr. Sen reported that gum disease (periodontitis) is extremely prevalent, occurring in around half the U.S. population. It is particularly prevalent in the southeastern part of the United States, known as the “Stroke Belt” because of a much higher incidence of stroke compared with the rest of the country. Gum disease is known to be associated with an increased risk of cardiovascular events and stroke.
For the study, 280 patients from the Stroke Belt area with a recent stroke or TIA and periodontal disease were randomly assigned to standard periodontal treatment or intensive periodontal treatment and followed for 1 year.
Standard treatment was composed of regular (every 3 months) supragingival removal of plaque and calculus; patients were also given a regular toothbrush and advice about dental care.
The intensive group received supragingival and subgingival removal of plaque and calculus (also every 3 months), extraction of hopeless teeth, locally delivered antibiotics. In addition, patients were given an electric toothbrush, mouthwash, and an air flosser for dental care.
All patients received comprehensive conventional stroke risk factor treatment.
The study had an adaptive randomization design to ensure both groups were balanced in terms of age, stroke causes, race, socioeconomic status, and stroke risk factors.
Results showed that after 1 year of follow-up, the primary outcome (stroke/myocardial infarction/death) had occurred in 7.7% of the intensive treatment group versus 12.3% of the standard care group, giving a hazard ratio of 0.65 (95% confidence interval, 0.30-1.38; P = .26).
But both groups had a much lower rate of recurrent events, compared with a historical control group which showed a 1-year rate of stroke/MI/death of 24%. The historical controls were part of an observational study that the same group of researchers conducted previously in a similar population.
In both standard treatment and intensive treatment groups, the combined number of dental visits strongly correlated with a reduction in cardiovascular events. Of the study participants, 65% attended all five visits, 25% attended two to four, and 10% did not attend any after the baseline assessment.
Those who attended all visits in the year had a rate of stroke/MI/death at 1 year of 8%. And those who did not attend any further visits after the baseline visit had an event rate of 25% at 1-year follow-up, which Dr. Sen noted was very similar to that of the historical controls. The P value for this trend was “very significant” (P = .0017), he said.
Secondary outcomes showed a reduction in blood pressure, A1c levels, carotid intima-media thickness, and better lipid profiles in all patients who underwent treatment – in both standard treatment and intensive treatment.
A new part of routine post-stroke care?
“Previous data on how gum disease and periodontal treatment relates to cardiovascular outcomes have all come from observational studies. They have shown that regular dental care is associated with reduced incidence of future cardiovascular events. But until now, we haven’t had any randomized data,” Dr. Sen noted.
He believes advice on oral and dental care should be part of routine clinical practice for patients who have suffered stroke. “This is not something we currently think about, but it could make a big difference in future event rates.”
Dr. Sen said the current study had raised interest in the topic, and his presentation was received with enthusiasm from the audience.
“We are in South Carolina in the Stroke Belt. Previous studies have shown that gum disease is very prevalent in this area. People in this area have a high risk of stroke, but we don’t know all the attributable risk factors. The traditional stroke risk factors do not seem to account for all the excess risk,” Dr. Sen said. “Periodontal disease could be one of the additional risk factors that accounts for the increased stroke risk in this population.”
“I believe doctors treating stroke patients should advise that they pay particular attention to oral care and visit the dentist frequently for periodontal treatment if they have gum disease. It is very unusual for people to get regular dental cleaning. They don’t understand that they need to do this,” he said.
But he acknowledges that larger studies are needed to show statistically significant results to be able to achieve a strong recommendation in the secondary prevention clinical guidelines.
“Even in individuals who haven’t had a stroke or cardiovascular event, population-based observational studies clearly show that gum infection is linked to future risk of myocardial infarction and stroke and that regular dental care (one or more visits per year) can reduce this risk. I don’t think we can do a randomized trial in the general population – that would need enormous numbers. We will have to rely on the observational studies here,” he added.
‘Promising’ results
Commenting on the current study, Louise McCullough, MD, ISC 2022 program chair, said she thought the results were promising.
“There was no difference in the intensive cleaning group versus standard cleaning, but the number of events was small, so it was underpowered to see differences. I think the main take home point is that both groups that came for dental visits had a much lower risk of another event than the group that did not show up for follow-up,” said Dr. McCullough, chair of the department of neurology, McGovern Medical School, University of Texas Health Science Center, Houston. “Clearly, seeing a provider made a difference. It is likely that contact with a dentist, getting blood pressure checked, etc., made a dramatic difference.”
The study was funded by the National Institute of Minority Health Disparity, Phillips Oral Healthcare, and Orapharma (which provided the study antibiotic medication).
A version of this article first appeared on Medscape.com.
The first randomized trial to investigate whether periodontal treatment can reduce future risk of cardiovascular events or stroke suggests some promise with this strategy.
The PREMIERS study, which was conducted in patients with a recent stroke or transient ischemic attack (TIA) who also had gum disease, did not show a statistically significant difference between intensive periodontal treatment and standard treatment in the rate of recurrent stroke, myocardial infarction (MI), or death in the 1-year follow-up, although there was a strong trend toward benefit in the intensive group.
Both groups had a much lower event rate compared with a historical control group made up of similar patients.
In addition, the number of dental visits significantly correlated with a reduction in the composite event rate in the study.
“My take-home message from this study is that periodontal treatment does appear to impact cardiovascular outcomes in stroke/TIA patients,” said lead author Souvik Sen, MD, MPH, professor of neurology at the University of South Carolina School of Medicine.
“Even standard periodontal care – a dental cleaning every 3 months – was beneficial.”
Dr. Sen presented the study at the hybrid International Stroke Conference (ISC), taking place in New Orleans and virtually.
“This was a very ambitious study, and it turned out to be very underpowered for the comparisons involved, but I was impressed that we saw such a strong trend toward benefit in the intensive group,” he said at the meeting, presented by the American Stroke Association, a division of the American Heart Association.
Dr. Sen explained that they initially set out to compare periodontal treatment with no treatment, but they were unable to have a control group who received no treatment for ethical reasons, so they ended up comparing standard treatment with intensive treatment.
“We probably needed a study of twice the size for that comparison. But our results are encouraging, and we now plan to do a larger study,” he said.
Dr. Sen reported that gum disease (periodontitis) is extremely prevalent, occurring in around half the U.S. population. It is particularly prevalent in the southeastern part of the United States, known as the “Stroke Belt” because of a much higher incidence of stroke compared with the rest of the country. Gum disease is known to be associated with an increased risk of cardiovascular events and stroke.
For the study, 280 patients from the Stroke Belt area with a recent stroke or TIA and periodontal disease were randomly assigned to standard periodontal treatment or intensive periodontal treatment and followed for 1 year.
Standard treatment was composed of regular (every 3 months) supragingival removal of plaque and calculus; patients were also given a regular toothbrush and advice about dental care.
The intensive group received supragingival and subgingival removal of plaque and calculus (also every 3 months), extraction of hopeless teeth, locally delivered antibiotics. In addition, patients were given an electric toothbrush, mouthwash, and an air flosser for dental care.
All patients received comprehensive conventional stroke risk factor treatment.
The study had an adaptive randomization design to ensure both groups were balanced in terms of age, stroke causes, race, socioeconomic status, and stroke risk factors.
Results showed that after 1 year of follow-up, the primary outcome (stroke/myocardial infarction/death) had occurred in 7.7% of the intensive treatment group versus 12.3% of the standard care group, giving a hazard ratio of 0.65 (95% confidence interval, 0.30-1.38; P = .26).
But both groups had a much lower rate of recurrent events, compared with a historical control group which showed a 1-year rate of stroke/MI/death of 24%. The historical controls were part of an observational study that the same group of researchers conducted previously in a similar population.
In both standard treatment and intensive treatment groups, the combined number of dental visits strongly correlated with a reduction in cardiovascular events. Of the study participants, 65% attended all five visits, 25% attended two to four, and 10% did not attend any after the baseline assessment.
Those who attended all visits in the year had a rate of stroke/MI/death at 1 year of 8%. And those who did not attend any further visits after the baseline visit had an event rate of 25% at 1-year follow-up, which Dr. Sen noted was very similar to that of the historical controls. The P value for this trend was “very significant” (P = .0017), he said.
Secondary outcomes showed a reduction in blood pressure, A1c levels, carotid intima-media thickness, and better lipid profiles in all patients who underwent treatment – in both standard treatment and intensive treatment.
A new part of routine post-stroke care?
“Previous data on how gum disease and periodontal treatment relates to cardiovascular outcomes have all come from observational studies. They have shown that regular dental care is associated with reduced incidence of future cardiovascular events. But until now, we haven’t had any randomized data,” Dr. Sen noted.
He believes advice on oral and dental care should be part of routine clinical practice for patients who have suffered stroke. “This is not something we currently think about, but it could make a big difference in future event rates.”
Dr. Sen said the current study had raised interest in the topic, and his presentation was received with enthusiasm from the audience.
“We are in South Carolina in the Stroke Belt. Previous studies have shown that gum disease is very prevalent in this area. People in this area have a high risk of stroke, but we don’t know all the attributable risk factors. The traditional stroke risk factors do not seem to account for all the excess risk,” Dr. Sen said. “Periodontal disease could be one of the additional risk factors that accounts for the increased stroke risk in this population.”
“I believe doctors treating stroke patients should advise that they pay particular attention to oral care and visit the dentist frequently for periodontal treatment if they have gum disease. It is very unusual for people to get regular dental cleaning. They don’t understand that they need to do this,” he said.
But he acknowledges that larger studies are needed to show statistically significant results to be able to achieve a strong recommendation in the secondary prevention clinical guidelines.
“Even in individuals who haven’t had a stroke or cardiovascular event, population-based observational studies clearly show that gum infection is linked to future risk of myocardial infarction and stroke and that regular dental care (one or more visits per year) can reduce this risk. I don’t think we can do a randomized trial in the general population – that would need enormous numbers. We will have to rely on the observational studies here,” he added.
‘Promising’ results
Commenting on the current study, Louise McCullough, MD, ISC 2022 program chair, said she thought the results were promising.
“There was no difference in the intensive cleaning group versus standard cleaning, but the number of events was small, so it was underpowered to see differences. I think the main take home point is that both groups that came for dental visits had a much lower risk of another event than the group that did not show up for follow-up,” said Dr. McCullough, chair of the department of neurology, McGovern Medical School, University of Texas Health Science Center, Houston. “Clearly, seeing a provider made a difference. It is likely that contact with a dentist, getting blood pressure checked, etc., made a dramatic difference.”
The study was funded by the National Institute of Minority Health Disparity, Phillips Oral Healthcare, and Orapharma (which provided the study antibiotic medication).
A version of this article first appeared on Medscape.com.
FROM ISC 2022