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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
Tenecteplase for stroke linked to reduced ICH risk
preliminary results from a large, multicenter registry study suggest.
“In clinical practice where centers are using tenecteplase, we’re seeing that the rate of symptomatic hemorrhage after getting a thrombolytic is half that with tenecteplase than with alteplase,” said lead author Steven J. Warach, MD, PhD, professor of neurology at Dell Medical School, University of Texas, Austin.
“For clinicians who have switched or are considering switching to tenecteplase, I think these results are very reassuring,” he said at the International Stroke Conference, presented by the American Stroke Association, a division of the American Heart Association.
Tenecteplase is a relatively new agent that is approved by the U.S. Food and Drug Administration to treat myocardial infarction but not ischemic stroke, although clinicians sometimes use it off-label for this purpose. American Heart Association guidelines recommend tenecteplase might be reasonable to consider for ischemic stroke in select patients.
The current standard of care for stroke is alteplase, which has been approved for this indication since 1996.
Five randomized clinical trials comparing the two thrombolytics weren’t large enough to make definitive conclusions about differences, said Dr. Warach. “The event rate for serious bleeding into the brain was thankfully low in both groups.”
Results from a meta-analysis that combined data from those five trials were also not definitive. “Numerically, it looked like the rate was lower for tenecteplase, but the sample size was just too low to make any statistically confident statement.”
However, tenecteplase has practical advantages over alteplase. Tenecteplase is a single bolus injection lasting 5 seconds while alteplase is administered by injection followed by an hour-long infusion.
Given these potential advantages, some centers have changed their practice and started using the newer drug beginning in July 2018.
The current study used an ongoing large registry to compare rates of symptomatic intracranial hemorrhage in patients treated with either of these drugs. The registry includes data collected July 2018 to June 2021 from various hospitals and programs in New Zealand, Australia, and the U.S.
Symptomatic intracranial hemorrhage was defined as a severe bleed causing pressure on the brain, extensive swelling, and worsening by at least four points on the National Institutes of Health Stroke Scale (NIHSS).
Researchers abstracted data from the various registries. As not all centers record data in the same format, statisticians then “cleaned” or harmonized the data to make it more standardized, said Dr. Warach.
They controlled for factors known to put a patient at higher risk for symptomatic hemorrhage, including age, sex, baseline NIHSS, and time to treatment.
Dr. Warach noted that at baseline, the tenecteplase group had higher values on most of these factors “that would predict intracranial hemorrhage.”
In an earlier analysis of 7,891 patients, the tenecteplase group was older (73 vs. 70 years; P < .001), less likely to be female (44.1% vs. 48.7%; P = .001), and had higher NIHSS scores (9 vs. 7; P < .001).
Also, a greater percentage of those in the tenecteplase group underwent mechanical thrombectomy (36.7% vs. 18.0%; P < .001). Dr. Warach explained that some centers would opt for tenecteplase if they knew the patient was a candidate for thrombectomy “because that was where the data was clearly strong and positive.”
An updated analysis included 9,238 patients – 7,313 who received alteplase and 1,925 tenecteplase. In the updated unadjusted analysis, the symptomatic intracranial hemorrhage rate was 3.6% for alteplase and 1.8% for tenecteplase (odds ratio, 0.49; P < .001). The adjusted OR was 0.42 (P < .001.)
The difference was even greater in those who underwent thrombectomy. For patients undergoing this procedure after a thrombolytic, the symptomatic intracranial hemorrhage rate was 5.9% for alteplase and 2.4% for tenecteplase.
“That even in those higher-risk patients we’re seeing an even greater difference is promising,” said Dr. Warach.
He and his colleagues plan to assess other potential benefits of tenecteplase, for example, the time it takes for patients to recover, “once we have all the data standardized and cleaned.”
Results of three large phase 3 trials comparing the two thrombolytics are expected within the next year or two, said Dr. Warach.
Joseph Broderick, MD, professor and director of the UC Gardner Neuroscience Institute, director of the National Coordinating Center for NIH’s StrokeNet, and professor of medicine at the University of Cincinnati College of Medicine, Cincinnati, stressed that for both drugs, speed is of the utmost importance to protect the brain.
“No matter which of these drugs is going to be used, the key thing is that they have to be used as quickly as possible,” he said.
Also important is imaging the brain before administering either of these medications to ensure the issue is an ischemic stroke and not an intracerebral hemorrhage, said Dr. Broderick. “If you have a broken blood vessel, you want to seal the leak, not break up the clot and make the bleeding worse.”
Dr. Warach receives payment as chair of the safety committee of another Genentech study comparing tenecteplase versus placebo in patients with large vessel occlusion whose stroke began more than 4.5 hours before treatment.
A version of this article first appeared on Medscape.com.
preliminary results from a large, multicenter registry study suggest.
“In clinical practice where centers are using tenecteplase, we’re seeing that the rate of symptomatic hemorrhage after getting a thrombolytic is half that with tenecteplase than with alteplase,” said lead author Steven J. Warach, MD, PhD, professor of neurology at Dell Medical School, University of Texas, Austin.
“For clinicians who have switched or are considering switching to tenecteplase, I think these results are very reassuring,” he said at the International Stroke Conference, presented by the American Stroke Association, a division of the American Heart Association.
Tenecteplase is a relatively new agent that is approved by the U.S. Food and Drug Administration to treat myocardial infarction but not ischemic stroke, although clinicians sometimes use it off-label for this purpose. American Heart Association guidelines recommend tenecteplase might be reasonable to consider for ischemic stroke in select patients.
The current standard of care for stroke is alteplase, which has been approved for this indication since 1996.
Five randomized clinical trials comparing the two thrombolytics weren’t large enough to make definitive conclusions about differences, said Dr. Warach. “The event rate for serious bleeding into the brain was thankfully low in both groups.”
Results from a meta-analysis that combined data from those five trials were also not definitive. “Numerically, it looked like the rate was lower for tenecteplase, but the sample size was just too low to make any statistically confident statement.”
However, tenecteplase has practical advantages over alteplase. Tenecteplase is a single bolus injection lasting 5 seconds while alteplase is administered by injection followed by an hour-long infusion.
Given these potential advantages, some centers have changed their practice and started using the newer drug beginning in July 2018.
The current study used an ongoing large registry to compare rates of symptomatic intracranial hemorrhage in patients treated with either of these drugs. The registry includes data collected July 2018 to June 2021 from various hospitals and programs in New Zealand, Australia, and the U.S.
Symptomatic intracranial hemorrhage was defined as a severe bleed causing pressure on the brain, extensive swelling, and worsening by at least four points on the National Institutes of Health Stroke Scale (NIHSS).
Researchers abstracted data from the various registries. As not all centers record data in the same format, statisticians then “cleaned” or harmonized the data to make it more standardized, said Dr. Warach.
They controlled for factors known to put a patient at higher risk for symptomatic hemorrhage, including age, sex, baseline NIHSS, and time to treatment.
Dr. Warach noted that at baseline, the tenecteplase group had higher values on most of these factors “that would predict intracranial hemorrhage.”
In an earlier analysis of 7,891 patients, the tenecteplase group was older (73 vs. 70 years; P < .001), less likely to be female (44.1% vs. 48.7%; P = .001), and had higher NIHSS scores (9 vs. 7; P < .001).
Also, a greater percentage of those in the tenecteplase group underwent mechanical thrombectomy (36.7% vs. 18.0%; P < .001). Dr. Warach explained that some centers would opt for tenecteplase if they knew the patient was a candidate for thrombectomy “because that was where the data was clearly strong and positive.”
An updated analysis included 9,238 patients – 7,313 who received alteplase and 1,925 tenecteplase. In the updated unadjusted analysis, the symptomatic intracranial hemorrhage rate was 3.6% for alteplase and 1.8% for tenecteplase (odds ratio, 0.49; P < .001). The adjusted OR was 0.42 (P < .001.)
The difference was even greater in those who underwent thrombectomy. For patients undergoing this procedure after a thrombolytic, the symptomatic intracranial hemorrhage rate was 5.9% for alteplase and 2.4% for tenecteplase.
“That even in those higher-risk patients we’re seeing an even greater difference is promising,” said Dr. Warach.
He and his colleagues plan to assess other potential benefits of tenecteplase, for example, the time it takes for patients to recover, “once we have all the data standardized and cleaned.”
Results of three large phase 3 trials comparing the two thrombolytics are expected within the next year or two, said Dr. Warach.
Joseph Broderick, MD, professor and director of the UC Gardner Neuroscience Institute, director of the National Coordinating Center for NIH’s StrokeNet, and professor of medicine at the University of Cincinnati College of Medicine, Cincinnati, stressed that for both drugs, speed is of the utmost importance to protect the brain.
“No matter which of these drugs is going to be used, the key thing is that they have to be used as quickly as possible,” he said.
Also important is imaging the brain before administering either of these medications to ensure the issue is an ischemic stroke and not an intracerebral hemorrhage, said Dr. Broderick. “If you have a broken blood vessel, you want to seal the leak, not break up the clot and make the bleeding worse.”
Dr. Warach receives payment as chair of the safety committee of another Genentech study comparing tenecteplase versus placebo in patients with large vessel occlusion whose stroke began more than 4.5 hours before treatment.
A version of this article first appeared on Medscape.com.
preliminary results from a large, multicenter registry study suggest.
“In clinical practice where centers are using tenecteplase, we’re seeing that the rate of symptomatic hemorrhage after getting a thrombolytic is half that with tenecteplase than with alteplase,” said lead author Steven J. Warach, MD, PhD, professor of neurology at Dell Medical School, University of Texas, Austin.
“For clinicians who have switched or are considering switching to tenecteplase, I think these results are very reassuring,” he said at the International Stroke Conference, presented by the American Stroke Association, a division of the American Heart Association.
Tenecteplase is a relatively new agent that is approved by the U.S. Food and Drug Administration to treat myocardial infarction but not ischemic stroke, although clinicians sometimes use it off-label for this purpose. American Heart Association guidelines recommend tenecteplase might be reasonable to consider for ischemic stroke in select patients.
The current standard of care for stroke is alteplase, which has been approved for this indication since 1996.
Five randomized clinical trials comparing the two thrombolytics weren’t large enough to make definitive conclusions about differences, said Dr. Warach. “The event rate for serious bleeding into the brain was thankfully low in both groups.”
Results from a meta-analysis that combined data from those five trials were also not definitive. “Numerically, it looked like the rate was lower for tenecteplase, but the sample size was just too low to make any statistically confident statement.”
However, tenecteplase has practical advantages over alteplase. Tenecteplase is a single bolus injection lasting 5 seconds while alteplase is administered by injection followed by an hour-long infusion.
Given these potential advantages, some centers have changed their practice and started using the newer drug beginning in July 2018.
The current study used an ongoing large registry to compare rates of symptomatic intracranial hemorrhage in patients treated with either of these drugs. The registry includes data collected July 2018 to June 2021 from various hospitals and programs in New Zealand, Australia, and the U.S.
Symptomatic intracranial hemorrhage was defined as a severe bleed causing pressure on the brain, extensive swelling, and worsening by at least four points on the National Institutes of Health Stroke Scale (NIHSS).
Researchers abstracted data from the various registries. As not all centers record data in the same format, statisticians then “cleaned” or harmonized the data to make it more standardized, said Dr. Warach.
They controlled for factors known to put a patient at higher risk for symptomatic hemorrhage, including age, sex, baseline NIHSS, and time to treatment.
Dr. Warach noted that at baseline, the tenecteplase group had higher values on most of these factors “that would predict intracranial hemorrhage.”
In an earlier analysis of 7,891 patients, the tenecteplase group was older (73 vs. 70 years; P < .001), less likely to be female (44.1% vs. 48.7%; P = .001), and had higher NIHSS scores (9 vs. 7; P < .001).
Also, a greater percentage of those in the tenecteplase group underwent mechanical thrombectomy (36.7% vs. 18.0%; P < .001). Dr. Warach explained that some centers would opt for tenecteplase if they knew the patient was a candidate for thrombectomy “because that was where the data was clearly strong and positive.”
An updated analysis included 9,238 patients – 7,313 who received alteplase and 1,925 tenecteplase. In the updated unadjusted analysis, the symptomatic intracranial hemorrhage rate was 3.6% for alteplase and 1.8% for tenecteplase (odds ratio, 0.49; P < .001). The adjusted OR was 0.42 (P < .001.)
The difference was even greater in those who underwent thrombectomy. For patients undergoing this procedure after a thrombolytic, the symptomatic intracranial hemorrhage rate was 5.9% for alteplase and 2.4% for tenecteplase.
“That even in those higher-risk patients we’re seeing an even greater difference is promising,” said Dr. Warach.
He and his colleagues plan to assess other potential benefits of tenecteplase, for example, the time it takes for patients to recover, “once we have all the data standardized and cleaned.”
Results of three large phase 3 trials comparing the two thrombolytics are expected within the next year or two, said Dr. Warach.
Joseph Broderick, MD, professor and director of the UC Gardner Neuroscience Institute, director of the National Coordinating Center for NIH’s StrokeNet, and professor of medicine at the University of Cincinnati College of Medicine, Cincinnati, stressed that for both drugs, speed is of the utmost importance to protect the brain.
“No matter which of these drugs is going to be used, the key thing is that they have to be used as quickly as possible,” he said.
Also important is imaging the brain before administering either of these medications to ensure the issue is an ischemic stroke and not an intracerebral hemorrhage, said Dr. Broderick. “If you have a broken blood vessel, you want to seal the leak, not break up the clot and make the bleeding worse.”
Dr. Warach receives payment as chair of the safety committee of another Genentech study comparing tenecteplase versus placebo in patients with large vessel occlusion whose stroke began more than 4.5 hours before treatment.
A version of this article first appeared on Medscape.com.
FROM ISC 2022
‘Remarkable’ benefit with intra-arterial tPA after stroke thrombectomy: CHOICE
in a new study.
The phase 2b CHOICE study was presented at the International Stroke Conference by Ángel Chamorro, MD, University of Barcelona, who received a round of applause as the results were revealed.
The study was also published online in JAMA to coincide with the presentation at the ISC.
The main results showed a remarkable and significant 18.4% absolute increase in the number of patients achieving an excellent neurologic outcome, defined as modified Rankin Scale (mRS) score of 0-1, after treatment with intra-arterial alteplase immediately following thrombectomy. This was despite the fact that the study was stopped early because of difficulty obtaining placebo supplies during the pandemic, having only enrolled 121 of the planned 200 patients.
This benefit was achieved without any increase in intracranial hemorrhage, which Dr. Chamorro described as “reassuring.”
He explained that although mechanical thrombectomy gives a high rate of successful reperfusion, only about 27% of patients achieve complete freedom of disability (mRS 0-1) at 3 months. He suggested that this may be the result of impaired reperfusion of the microcirculation despite complete recanalization of the occluded vessel.
The researchers postulated that thrombi could persist within the microcirculation in patients with normal or nearly normal cerebral angiograms at the end of thrombectomy and that these smaller thrombi may be dissolved by a dose of intra-arterial thrombolysis.
‘Dramatic and exciting results’
The CHOICE study was greeted with enthusiasm from commentators at the ISC meeting, which was presented by the American Stroke Association, a division of the American Heart Association. Louise McCullough, MD, chair of the late-breaking science session at which the study was presented and ISC program chair, described the results as “very dramatic and very exciting.”
“The CHOICE trial is going to be a highlight of the meeting because it could change care now,” Dr. McCullough said. “By just giving a little adjunctive tPA after the main clot is out, everybody seems to benefit, and there was no increased risk in bleeding. I think that’s the one that people are going to take back to their practice. But it was a very small trial, so you have to be cautious.”
And Peter Panagos, MD, professor of emergency medicine and neurology at Washington University School of Medicine, St. Louis, said: “It’s great to see this study. The 18% treatment effect is very impressive.”
Dr. Panagos added: “This study addresses a well-described finding from many of the interventional trials, that despite excellent outcomes in recanalization, patients don’t do as well as predicted. The thought is that either re-stenosis or propagation of smaller clots downstream from the original clot in small-caliber vessels [is what] causes additional, unintended damage. The use of intra-arterial thrombolysis after recanalization may assist in dissolving those smaller, downstream clots and debris and improve outcomes.”
But he pointed out that enthusiasm over these results must be matched with some concerns, including the small study size and wide confidence intervals – so larger, randomized studies will be required to confirm and change current clinical practice.
An abbreviated phase 2b trial
The CHOICE trial was conducted in seven centers in Catalonia, Spain.
For the study, patients with large vessel occlusion acute ischemic stroke treated with thrombectomy within 24 hours after stroke onset and who had achieved successful reperfusion (an expanded TICI angiographic score of 2b50 to 3) were randomly assigned to receive intra-arterial alteplase (0.225 mg/kg; maximum dose, 22.5 mg) infused over 15 to 30 minutes or placebo.
Because of the lack of continued availability of placebo supplies, the study had to be stopped early after 121 patients were enrolled (65 alteplase; 56 placebo), and after a few dropouts who did not receive treatment, the analysis was performed on 61 patients who received alteplase and 52 given placebo.
Results showed that the proportion of patients with an mRS score of 0 or 1 at 90 days was 59% (36/61) with alteplase and 40.4% (21/52) with placebo (adjusted risk difference, 18.4%; 95% confidence interval, 0.3%-36.4%; P = .047).
The proportion of patients with symptomatic intracranial hemorrhage within 24 hours was 0% with alteplase and 3.8% with placebo (risk difference, −3.8%; 95% CI, −13.2% to 2.5%).
Mortality at 90 days was 8% with alteplase and 15% with placebo (risk difference, −7.2%; 95% CI, −19.2% to 4.8%).
The improved clinical outcomes in the alteplase group were seen despite only minor differences between the treatment groups in angiographic scores or in other surrogate imaging, Dr. Chamorro pointed out, suggesting that the improved functional outcome may be explained by an amelioration in the microcirculatory reperfusion.
He said the study also supported the safety of intra-arterial alteplase infusion for 15-30 minutes at the dose used. Of note, 60% of the study population had also received IV alteplase before thrombectomy.
In the JAMA study, the authors report that current guidelines recommend that all eligible patients receive intravenous alteplase before thrombectomy, and the results of this trial do not contradict this recommendation.
“The study results support the safety of adjunct intra-arterial alteplase in patients with successful reperfusion at the end of thrombectomy, including in patients treated previously with intravenous alteplase, although the findings on effectiveness should be interpreted as preliminary, requiring replication before any recommendations for practice change,” they concluded.
Dr. Chamorro said that his group was now planning a second larger trial, CHOICE-2.
In an accompanying editorial in JAMA, Pooja Khatri, MD, MSc, University of Cincinnati, said “the 18% treatment effect observed in this 113-patient trial is remarkable.”
However, she cautions that consideration of its clinical implications must be tempered because of the lack of precision of the effect estimate, given wide 95% confidence intervals, the small sample size, and the observation that trials with early termination are well known to overestimate treatment effect.
But she acknowledges that the results suggest “that additional reperfusion therapy may be warranted after relatively successful mechanical thrombectomy of large vessel occlusions, whether to treat the residual primary thrombus, more distal arterial occlusions, or perhaps even microthromboses.”
Dr. Khatri noted that this approach runs counter to the recent movement to consider bypass of intravenous alteplase altogether in thrombectomy-eligible patients and suggests that additional or perhaps more targeted thrombolysis will be the most beneficial approach.
Further studies testing current thrombolytic agents, novel clot-dissolving agents, and other adjunctive antithrombotic and anti-inflammatory agents are needed, she concluded.
A version of this article first appeared on Medscape.com.
in a new study.
The phase 2b CHOICE study was presented at the International Stroke Conference by Ángel Chamorro, MD, University of Barcelona, who received a round of applause as the results were revealed.
The study was also published online in JAMA to coincide with the presentation at the ISC.
The main results showed a remarkable and significant 18.4% absolute increase in the number of patients achieving an excellent neurologic outcome, defined as modified Rankin Scale (mRS) score of 0-1, after treatment with intra-arterial alteplase immediately following thrombectomy. This was despite the fact that the study was stopped early because of difficulty obtaining placebo supplies during the pandemic, having only enrolled 121 of the planned 200 patients.
This benefit was achieved without any increase in intracranial hemorrhage, which Dr. Chamorro described as “reassuring.”
He explained that although mechanical thrombectomy gives a high rate of successful reperfusion, only about 27% of patients achieve complete freedom of disability (mRS 0-1) at 3 months. He suggested that this may be the result of impaired reperfusion of the microcirculation despite complete recanalization of the occluded vessel.
The researchers postulated that thrombi could persist within the microcirculation in patients with normal or nearly normal cerebral angiograms at the end of thrombectomy and that these smaller thrombi may be dissolved by a dose of intra-arterial thrombolysis.
‘Dramatic and exciting results’
The CHOICE study was greeted with enthusiasm from commentators at the ISC meeting, which was presented by the American Stroke Association, a division of the American Heart Association. Louise McCullough, MD, chair of the late-breaking science session at which the study was presented and ISC program chair, described the results as “very dramatic and very exciting.”
“The CHOICE trial is going to be a highlight of the meeting because it could change care now,” Dr. McCullough said. “By just giving a little adjunctive tPA after the main clot is out, everybody seems to benefit, and there was no increased risk in bleeding. I think that’s the one that people are going to take back to their practice. But it was a very small trial, so you have to be cautious.”
And Peter Panagos, MD, professor of emergency medicine and neurology at Washington University School of Medicine, St. Louis, said: “It’s great to see this study. The 18% treatment effect is very impressive.”
Dr. Panagos added: “This study addresses a well-described finding from many of the interventional trials, that despite excellent outcomes in recanalization, patients don’t do as well as predicted. The thought is that either re-stenosis or propagation of smaller clots downstream from the original clot in small-caliber vessels [is what] causes additional, unintended damage. The use of intra-arterial thrombolysis after recanalization may assist in dissolving those smaller, downstream clots and debris and improve outcomes.”
But he pointed out that enthusiasm over these results must be matched with some concerns, including the small study size and wide confidence intervals – so larger, randomized studies will be required to confirm and change current clinical practice.
An abbreviated phase 2b trial
The CHOICE trial was conducted in seven centers in Catalonia, Spain.
For the study, patients with large vessel occlusion acute ischemic stroke treated with thrombectomy within 24 hours after stroke onset and who had achieved successful reperfusion (an expanded TICI angiographic score of 2b50 to 3) were randomly assigned to receive intra-arterial alteplase (0.225 mg/kg; maximum dose, 22.5 mg) infused over 15 to 30 minutes or placebo.
Because of the lack of continued availability of placebo supplies, the study had to be stopped early after 121 patients were enrolled (65 alteplase; 56 placebo), and after a few dropouts who did not receive treatment, the analysis was performed on 61 patients who received alteplase and 52 given placebo.
Results showed that the proportion of patients with an mRS score of 0 or 1 at 90 days was 59% (36/61) with alteplase and 40.4% (21/52) with placebo (adjusted risk difference, 18.4%; 95% confidence interval, 0.3%-36.4%; P = .047).
The proportion of patients with symptomatic intracranial hemorrhage within 24 hours was 0% with alteplase and 3.8% with placebo (risk difference, −3.8%; 95% CI, −13.2% to 2.5%).
Mortality at 90 days was 8% with alteplase and 15% with placebo (risk difference, −7.2%; 95% CI, −19.2% to 4.8%).
The improved clinical outcomes in the alteplase group were seen despite only minor differences between the treatment groups in angiographic scores or in other surrogate imaging, Dr. Chamorro pointed out, suggesting that the improved functional outcome may be explained by an amelioration in the microcirculatory reperfusion.
He said the study also supported the safety of intra-arterial alteplase infusion for 15-30 minutes at the dose used. Of note, 60% of the study population had also received IV alteplase before thrombectomy.
In the JAMA study, the authors report that current guidelines recommend that all eligible patients receive intravenous alteplase before thrombectomy, and the results of this trial do not contradict this recommendation.
“The study results support the safety of adjunct intra-arterial alteplase in patients with successful reperfusion at the end of thrombectomy, including in patients treated previously with intravenous alteplase, although the findings on effectiveness should be interpreted as preliminary, requiring replication before any recommendations for practice change,” they concluded.
Dr. Chamorro said that his group was now planning a second larger trial, CHOICE-2.
In an accompanying editorial in JAMA, Pooja Khatri, MD, MSc, University of Cincinnati, said “the 18% treatment effect observed in this 113-patient trial is remarkable.”
However, she cautions that consideration of its clinical implications must be tempered because of the lack of precision of the effect estimate, given wide 95% confidence intervals, the small sample size, and the observation that trials with early termination are well known to overestimate treatment effect.
But she acknowledges that the results suggest “that additional reperfusion therapy may be warranted after relatively successful mechanical thrombectomy of large vessel occlusions, whether to treat the residual primary thrombus, more distal arterial occlusions, or perhaps even microthromboses.”
Dr. Khatri noted that this approach runs counter to the recent movement to consider bypass of intravenous alteplase altogether in thrombectomy-eligible patients and suggests that additional or perhaps more targeted thrombolysis will be the most beneficial approach.
Further studies testing current thrombolytic agents, novel clot-dissolving agents, and other adjunctive antithrombotic and anti-inflammatory agents are needed, she concluded.
A version of this article first appeared on Medscape.com.
in a new study.
The phase 2b CHOICE study was presented at the International Stroke Conference by Ángel Chamorro, MD, University of Barcelona, who received a round of applause as the results were revealed.
The study was also published online in JAMA to coincide with the presentation at the ISC.
The main results showed a remarkable and significant 18.4% absolute increase in the number of patients achieving an excellent neurologic outcome, defined as modified Rankin Scale (mRS) score of 0-1, after treatment with intra-arterial alteplase immediately following thrombectomy. This was despite the fact that the study was stopped early because of difficulty obtaining placebo supplies during the pandemic, having only enrolled 121 of the planned 200 patients.
This benefit was achieved without any increase in intracranial hemorrhage, which Dr. Chamorro described as “reassuring.”
He explained that although mechanical thrombectomy gives a high rate of successful reperfusion, only about 27% of patients achieve complete freedom of disability (mRS 0-1) at 3 months. He suggested that this may be the result of impaired reperfusion of the microcirculation despite complete recanalization of the occluded vessel.
The researchers postulated that thrombi could persist within the microcirculation in patients with normal or nearly normal cerebral angiograms at the end of thrombectomy and that these smaller thrombi may be dissolved by a dose of intra-arterial thrombolysis.
‘Dramatic and exciting results’
The CHOICE study was greeted with enthusiasm from commentators at the ISC meeting, which was presented by the American Stroke Association, a division of the American Heart Association. Louise McCullough, MD, chair of the late-breaking science session at which the study was presented and ISC program chair, described the results as “very dramatic and very exciting.”
“The CHOICE trial is going to be a highlight of the meeting because it could change care now,” Dr. McCullough said. “By just giving a little adjunctive tPA after the main clot is out, everybody seems to benefit, and there was no increased risk in bleeding. I think that’s the one that people are going to take back to their practice. But it was a very small trial, so you have to be cautious.”
And Peter Panagos, MD, professor of emergency medicine and neurology at Washington University School of Medicine, St. Louis, said: “It’s great to see this study. The 18% treatment effect is very impressive.”
Dr. Panagos added: “This study addresses a well-described finding from many of the interventional trials, that despite excellent outcomes in recanalization, patients don’t do as well as predicted. The thought is that either re-stenosis or propagation of smaller clots downstream from the original clot in small-caliber vessels [is what] causes additional, unintended damage. The use of intra-arterial thrombolysis after recanalization may assist in dissolving those smaller, downstream clots and debris and improve outcomes.”
But he pointed out that enthusiasm over these results must be matched with some concerns, including the small study size and wide confidence intervals – so larger, randomized studies will be required to confirm and change current clinical practice.
An abbreviated phase 2b trial
The CHOICE trial was conducted in seven centers in Catalonia, Spain.
For the study, patients with large vessel occlusion acute ischemic stroke treated with thrombectomy within 24 hours after stroke onset and who had achieved successful reperfusion (an expanded TICI angiographic score of 2b50 to 3) were randomly assigned to receive intra-arterial alteplase (0.225 mg/kg; maximum dose, 22.5 mg) infused over 15 to 30 minutes or placebo.
Because of the lack of continued availability of placebo supplies, the study had to be stopped early after 121 patients were enrolled (65 alteplase; 56 placebo), and after a few dropouts who did not receive treatment, the analysis was performed on 61 patients who received alteplase and 52 given placebo.
Results showed that the proportion of patients with an mRS score of 0 or 1 at 90 days was 59% (36/61) with alteplase and 40.4% (21/52) with placebo (adjusted risk difference, 18.4%; 95% confidence interval, 0.3%-36.4%; P = .047).
The proportion of patients with symptomatic intracranial hemorrhage within 24 hours was 0% with alteplase and 3.8% with placebo (risk difference, −3.8%; 95% CI, −13.2% to 2.5%).
Mortality at 90 days was 8% with alteplase and 15% with placebo (risk difference, −7.2%; 95% CI, −19.2% to 4.8%).
The improved clinical outcomes in the alteplase group were seen despite only minor differences between the treatment groups in angiographic scores or in other surrogate imaging, Dr. Chamorro pointed out, suggesting that the improved functional outcome may be explained by an amelioration in the microcirculatory reperfusion.
He said the study also supported the safety of intra-arterial alteplase infusion for 15-30 minutes at the dose used. Of note, 60% of the study population had also received IV alteplase before thrombectomy.
In the JAMA study, the authors report that current guidelines recommend that all eligible patients receive intravenous alteplase before thrombectomy, and the results of this trial do not contradict this recommendation.
“The study results support the safety of adjunct intra-arterial alteplase in patients with successful reperfusion at the end of thrombectomy, including in patients treated previously with intravenous alteplase, although the findings on effectiveness should be interpreted as preliminary, requiring replication before any recommendations for practice change,” they concluded.
Dr. Chamorro said that his group was now planning a second larger trial, CHOICE-2.
In an accompanying editorial in JAMA, Pooja Khatri, MD, MSc, University of Cincinnati, said “the 18% treatment effect observed in this 113-patient trial is remarkable.”
However, she cautions that consideration of its clinical implications must be tempered because of the lack of precision of the effect estimate, given wide 95% confidence intervals, the small sample size, and the observation that trials with early termination are well known to overestimate treatment effect.
But she acknowledges that the results suggest “that additional reperfusion therapy may be warranted after relatively successful mechanical thrombectomy of large vessel occlusions, whether to treat the residual primary thrombus, more distal arterial occlusions, or perhaps even microthromboses.”
Dr. Khatri noted that this approach runs counter to the recent movement to consider bypass of intravenous alteplase altogether in thrombectomy-eligible patients and suggests that additional or perhaps more targeted thrombolysis will be the most beneficial approach.
Further studies testing current thrombolytic agents, novel clot-dissolving agents, and other adjunctive antithrombotic and anti-inflammatory agents are needed, she concluded.
A version of this article first appeared on Medscape.com.
FROM ISC 2022
New stroke risk score developed for COVID patients
Researchers have developed a quick and easy scoring system to predict which hospitalized COVID-19 patients are more at risk for stroke.
“The system is simple. You can calculate the points in 5 seconds and then predict the chances the patient will have a stroke,” Alexander E. Merkler, MD, assistant professor of neurology at Weill Cornell Medical College/NewYork-Presbyterian Hospital, and lead author of a study of the system, told this news organization.
The new system will allow clinicians to stratify patients and lead to closer monitoring of those at highest risk for stroke, said Dr. Merkler.
The study was presented during the International Stroke Conference, presented by the American Stroke Association, a division of the American Heart Association.
Some, but not all, studies suggest COVID-19 increases the risk of stroke and worsens stroke outcomes, and the association isn’t clear, investigators note.
Researchers used the American Heart Association Get With the Guidelines COVID-19 cardiovascular disease registry for this analysis. They evaluated 21,420 adult patients (mean age 61 years, 54% men), who were hospitalized with COVID-19 at 122 centers from March 2020 to March 2021.
Investigators tapped into the vast amounts of data in this registry on different variables, including demographics, comorbidities, and lab values.
The outcome was a cerebrovascular event, defined as any ischemic or hemorrhagic stroke, transient ischemic attack (TIA), or cerebral vein thrombosis. Of the total hospitalized COVID-19 population, 312 (1.5%) had a cerebrovascular event.
Researchers first used standard statistical models to determine which risk factors are most associated with the development of stroke. They identified six such factors:
- history of stroke
- no fever at the time of hospital admission
- no history of pulmonary disease
- high white blood cell count
- history of hypertension
- high systolic blood pressure at the time of hospital admission
That the list of risk factors included absence of fever and no history of pulmonary disease was somewhat surprising, said Dr. Merkler, but there may be possible explanations, he added.
A high fever is an inflammatory response, and perhaps patients who aren’t responding appropriately “could be sicker in general and have a poor immune system, and thereby be at increased risk for stroke,” said Dr. Merkler.
In the case of pulmonary disease, patients without a history who are admitted for COVID “may have an extremely high burden of COVID, or are extremely sick, and that’s why they’re at higher risk for stroke.”
The scoring system assigns points for each variable, with more points conferring a higher risk of stroke. For example, someone who has 0-1 points has 0.2% risk of having a stroke, and someone with 4-6 points has 2% to 3% risk, said Dr. Merkler.
“So, we’re talking about a 10- to 15-fold increased risk of having a stroke with 4 to 6 versus 0 to 1 variables.”
The accuracy of the risk stratification score (C-statistic of 0.66; 95% confidence interval, 0.60-0.72) is “fairly good or modestly good,” said Dr. Merkler.
A patient with a score of 5 or 6 may need more vigilant monitoring to make sure symptoms are caught early and therapies such as thrombolytics and thrombectomy are readily available, he added.
Researchers also used a sophisticated machine-learning approach where a computer takes all the variables and identifies the best algorithm to predict stroke.
“The machine-learning algorithm was basically just as good as our standard model; it was almost identical,” said Dr. Merkler.
Outside of COVID, other scoring systems are used to predict stroke. For example, the ABCD2 score uses various factors to predict risk of recurrent stroke.
Philip B. Gorelick, MD, adjunct professor, Northwestern University Feinberg School of Medicine, Chicago, said the results are promising, as they may lead to identifying modifiable factors to prevent stroke.
Dr. Gorelick noted that the authors identified risk factors to predict risk of stroke “after an extensive analysis of baseline factors that included an internal validation process.”
The finding that no fever and no history of pulmonary disease were included in those risk factors was “unexpected,” said Dr. Gorelick, who is also medical director of the Hauenstein Neuroscience Center in Grand Rapids, Michigan. “This may reflect the baseline timing of data collection.”
He added further validation of the results in other data sets “will be useful to determine the consistency of the predictive model and its potential value in general practice.”
Louise D. McCullough, MD, PhD, professor and chair of neurology, McGovern Medical School, The University of Texas Health Science Center, Houston, said the association between stroke risk and COVID exposure “has been very unclear.”
“Some people find a very strong association between stroke and COVID, some do not,” said Dr. McCullough, who served as the chair of the ISC 2022 meeting.
This new study looking at a risk stratification model for COVID patients was “very nicely done,” she added.
“They used the American Heart Association Get With The Guidelines COVID registry, which was an amazing feat that was done very quickly by the AHA to establish COVID reporting in the Get With The Guidelines data, allowing us to really look at other factors related to stroke that are in this unique database.”
The study received funding support from the American Stroke Association. Dr. Merkler has received funding from the American Heart Association and the Leon Levy Foundation. Dr. Gorelick was not involved in the study and has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Researchers have developed a quick and easy scoring system to predict which hospitalized COVID-19 patients are more at risk for stroke.
“The system is simple. You can calculate the points in 5 seconds and then predict the chances the patient will have a stroke,” Alexander E. Merkler, MD, assistant professor of neurology at Weill Cornell Medical College/NewYork-Presbyterian Hospital, and lead author of a study of the system, told this news organization.
The new system will allow clinicians to stratify patients and lead to closer monitoring of those at highest risk for stroke, said Dr. Merkler.
The study was presented during the International Stroke Conference, presented by the American Stroke Association, a division of the American Heart Association.
Some, but not all, studies suggest COVID-19 increases the risk of stroke and worsens stroke outcomes, and the association isn’t clear, investigators note.
Researchers used the American Heart Association Get With the Guidelines COVID-19 cardiovascular disease registry for this analysis. They evaluated 21,420 adult patients (mean age 61 years, 54% men), who were hospitalized with COVID-19 at 122 centers from March 2020 to March 2021.
Investigators tapped into the vast amounts of data in this registry on different variables, including demographics, comorbidities, and lab values.
The outcome was a cerebrovascular event, defined as any ischemic or hemorrhagic stroke, transient ischemic attack (TIA), or cerebral vein thrombosis. Of the total hospitalized COVID-19 population, 312 (1.5%) had a cerebrovascular event.
Researchers first used standard statistical models to determine which risk factors are most associated with the development of stroke. They identified six such factors:
- history of stroke
- no fever at the time of hospital admission
- no history of pulmonary disease
- high white blood cell count
- history of hypertension
- high systolic blood pressure at the time of hospital admission
That the list of risk factors included absence of fever and no history of pulmonary disease was somewhat surprising, said Dr. Merkler, but there may be possible explanations, he added.
A high fever is an inflammatory response, and perhaps patients who aren’t responding appropriately “could be sicker in general and have a poor immune system, and thereby be at increased risk for stroke,” said Dr. Merkler.
In the case of pulmonary disease, patients without a history who are admitted for COVID “may have an extremely high burden of COVID, or are extremely sick, and that’s why they’re at higher risk for stroke.”
The scoring system assigns points for each variable, with more points conferring a higher risk of stroke. For example, someone who has 0-1 points has 0.2% risk of having a stroke, and someone with 4-6 points has 2% to 3% risk, said Dr. Merkler.
“So, we’re talking about a 10- to 15-fold increased risk of having a stroke with 4 to 6 versus 0 to 1 variables.”
The accuracy of the risk stratification score (C-statistic of 0.66; 95% confidence interval, 0.60-0.72) is “fairly good or modestly good,” said Dr. Merkler.
A patient with a score of 5 or 6 may need more vigilant monitoring to make sure symptoms are caught early and therapies such as thrombolytics and thrombectomy are readily available, he added.
Researchers also used a sophisticated machine-learning approach where a computer takes all the variables and identifies the best algorithm to predict stroke.
“The machine-learning algorithm was basically just as good as our standard model; it was almost identical,” said Dr. Merkler.
Outside of COVID, other scoring systems are used to predict stroke. For example, the ABCD2 score uses various factors to predict risk of recurrent stroke.
Philip B. Gorelick, MD, adjunct professor, Northwestern University Feinberg School of Medicine, Chicago, said the results are promising, as they may lead to identifying modifiable factors to prevent stroke.
Dr. Gorelick noted that the authors identified risk factors to predict risk of stroke “after an extensive analysis of baseline factors that included an internal validation process.”
The finding that no fever and no history of pulmonary disease were included in those risk factors was “unexpected,” said Dr. Gorelick, who is also medical director of the Hauenstein Neuroscience Center in Grand Rapids, Michigan. “This may reflect the baseline timing of data collection.”
He added further validation of the results in other data sets “will be useful to determine the consistency of the predictive model and its potential value in general practice.”
Louise D. McCullough, MD, PhD, professor and chair of neurology, McGovern Medical School, The University of Texas Health Science Center, Houston, said the association between stroke risk and COVID exposure “has been very unclear.”
“Some people find a very strong association between stroke and COVID, some do not,” said Dr. McCullough, who served as the chair of the ISC 2022 meeting.
This new study looking at a risk stratification model for COVID patients was “very nicely done,” she added.
“They used the American Heart Association Get With The Guidelines COVID registry, which was an amazing feat that was done very quickly by the AHA to establish COVID reporting in the Get With The Guidelines data, allowing us to really look at other factors related to stroke that are in this unique database.”
The study received funding support from the American Stroke Association. Dr. Merkler has received funding from the American Heart Association and the Leon Levy Foundation. Dr. Gorelick was not involved in the study and has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Researchers have developed a quick and easy scoring system to predict which hospitalized COVID-19 patients are more at risk for stroke.
“The system is simple. You can calculate the points in 5 seconds and then predict the chances the patient will have a stroke,” Alexander E. Merkler, MD, assistant professor of neurology at Weill Cornell Medical College/NewYork-Presbyterian Hospital, and lead author of a study of the system, told this news organization.
The new system will allow clinicians to stratify patients and lead to closer monitoring of those at highest risk for stroke, said Dr. Merkler.
The study was presented during the International Stroke Conference, presented by the American Stroke Association, a division of the American Heart Association.
Some, but not all, studies suggest COVID-19 increases the risk of stroke and worsens stroke outcomes, and the association isn’t clear, investigators note.
Researchers used the American Heart Association Get With the Guidelines COVID-19 cardiovascular disease registry for this analysis. They evaluated 21,420 adult patients (mean age 61 years, 54% men), who were hospitalized with COVID-19 at 122 centers from March 2020 to March 2021.
Investigators tapped into the vast amounts of data in this registry on different variables, including demographics, comorbidities, and lab values.
The outcome was a cerebrovascular event, defined as any ischemic or hemorrhagic stroke, transient ischemic attack (TIA), or cerebral vein thrombosis. Of the total hospitalized COVID-19 population, 312 (1.5%) had a cerebrovascular event.
Researchers first used standard statistical models to determine which risk factors are most associated with the development of stroke. They identified six such factors:
- history of stroke
- no fever at the time of hospital admission
- no history of pulmonary disease
- high white blood cell count
- history of hypertension
- high systolic blood pressure at the time of hospital admission
That the list of risk factors included absence of fever and no history of pulmonary disease was somewhat surprising, said Dr. Merkler, but there may be possible explanations, he added.
A high fever is an inflammatory response, and perhaps patients who aren’t responding appropriately “could be sicker in general and have a poor immune system, and thereby be at increased risk for stroke,” said Dr. Merkler.
In the case of pulmonary disease, patients without a history who are admitted for COVID “may have an extremely high burden of COVID, or are extremely sick, and that’s why they’re at higher risk for stroke.”
The scoring system assigns points for each variable, with more points conferring a higher risk of stroke. For example, someone who has 0-1 points has 0.2% risk of having a stroke, and someone with 4-6 points has 2% to 3% risk, said Dr. Merkler.
“So, we’re talking about a 10- to 15-fold increased risk of having a stroke with 4 to 6 versus 0 to 1 variables.”
The accuracy of the risk stratification score (C-statistic of 0.66; 95% confidence interval, 0.60-0.72) is “fairly good or modestly good,” said Dr. Merkler.
A patient with a score of 5 or 6 may need more vigilant monitoring to make sure symptoms are caught early and therapies such as thrombolytics and thrombectomy are readily available, he added.
Researchers also used a sophisticated machine-learning approach where a computer takes all the variables and identifies the best algorithm to predict stroke.
“The machine-learning algorithm was basically just as good as our standard model; it was almost identical,” said Dr. Merkler.
Outside of COVID, other scoring systems are used to predict stroke. For example, the ABCD2 score uses various factors to predict risk of recurrent stroke.
Philip B. Gorelick, MD, adjunct professor, Northwestern University Feinberg School of Medicine, Chicago, said the results are promising, as they may lead to identifying modifiable factors to prevent stroke.
Dr. Gorelick noted that the authors identified risk factors to predict risk of stroke “after an extensive analysis of baseline factors that included an internal validation process.”
The finding that no fever and no history of pulmonary disease were included in those risk factors was “unexpected,” said Dr. Gorelick, who is also medical director of the Hauenstein Neuroscience Center in Grand Rapids, Michigan. “This may reflect the baseline timing of data collection.”
He added further validation of the results in other data sets “will be useful to determine the consistency of the predictive model and its potential value in general practice.”
Louise D. McCullough, MD, PhD, professor and chair of neurology, McGovern Medical School, The University of Texas Health Science Center, Houston, said the association between stroke risk and COVID exposure “has been very unclear.”
“Some people find a very strong association between stroke and COVID, some do not,” said Dr. McCullough, who served as the chair of the ISC 2022 meeting.
This new study looking at a risk stratification model for COVID patients was “very nicely done,” she added.
“They used the American Heart Association Get With The Guidelines COVID registry, which was an amazing feat that was done very quickly by the AHA to establish COVID reporting in the Get With The Guidelines data, allowing us to really look at other factors related to stroke that are in this unique database.”
The study received funding support from the American Stroke Association. Dr. Merkler has received funding from the American Heart Association and the Leon Levy Foundation. Dr. Gorelick was not involved in the study and has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ISC 2022
Novel drug targets raised Lp(a): topline results released
Topline results from the phase 1 APOLLO study of SLN360, a short interfering ribonucleic acid (siRNA) targeting lipoprotein(a), showed it significantly reduced Lp(a) in a dose-dependent manner from 46% to up to 98%.
Reductions of up to 81% were maintained out to 150 days, according to a release from the developer of the drug, Silence Therapeutics.
High Lp(a) affects about one in five people worldwide and is a genetic risk factor for cardiovascular disease. There are no approved medications that selectively lower Lp(a), and levels cannot be significantly modified through lifestyle changes or any approved medications.
SLN360 is a siRNA that is designed to lower Lp(a) production by using the body’s natural process of RNA interference to target and silence messenger RNA transcribed from the LPA gene in liver cells.
The first-in-human APOLLO trial evaluated 32 patients with serum Lp(a) concentrations of at least 150 nmol/L and no cardiovascular disease who received a single subcutaneous dose of SLN360 (30 mg, 100 mg, less than or equal to 300 mg, or less than or equal to 600 mg) or placebo and were followed for up to 150 days.
No clinically important safety concerns were identified, although low-grade adverse events at the injection site occurred, most prominently at the highest dose, according to the company.
Study follow-up has been extended to 1 year. Patient enrollment continues in the multiple-ascending dose portion of the phase 1 study in patients with high Lp(a) and a confirmed history of stable atherosclerotic cardiovascular disease, the company statement notes.
Detailed results from APOLLO will be presented in a late-breaking clinical trials session at the American College of Cardiology Annual Scientific Session on April 3 by principal investigator Steven E. Nissen, MD, Cleveland Clinic.
A version of this article first appeared on Medscape.com.
Topline results from the phase 1 APOLLO study of SLN360, a short interfering ribonucleic acid (siRNA) targeting lipoprotein(a), showed it significantly reduced Lp(a) in a dose-dependent manner from 46% to up to 98%.
Reductions of up to 81% were maintained out to 150 days, according to a release from the developer of the drug, Silence Therapeutics.
High Lp(a) affects about one in five people worldwide and is a genetic risk factor for cardiovascular disease. There are no approved medications that selectively lower Lp(a), and levels cannot be significantly modified through lifestyle changes or any approved medications.
SLN360 is a siRNA that is designed to lower Lp(a) production by using the body’s natural process of RNA interference to target and silence messenger RNA transcribed from the LPA gene in liver cells.
The first-in-human APOLLO trial evaluated 32 patients with serum Lp(a) concentrations of at least 150 nmol/L and no cardiovascular disease who received a single subcutaneous dose of SLN360 (30 mg, 100 mg, less than or equal to 300 mg, or less than or equal to 600 mg) or placebo and were followed for up to 150 days.
No clinically important safety concerns were identified, although low-grade adverse events at the injection site occurred, most prominently at the highest dose, according to the company.
Study follow-up has been extended to 1 year. Patient enrollment continues in the multiple-ascending dose portion of the phase 1 study in patients with high Lp(a) and a confirmed history of stable atherosclerotic cardiovascular disease, the company statement notes.
Detailed results from APOLLO will be presented in a late-breaking clinical trials session at the American College of Cardiology Annual Scientific Session on April 3 by principal investigator Steven E. Nissen, MD, Cleveland Clinic.
A version of this article first appeared on Medscape.com.
Topline results from the phase 1 APOLLO study of SLN360, a short interfering ribonucleic acid (siRNA) targeting lipoprotein(a), showed it significantly reduced Lp(a) in a dose-dependent manner from 46% to up to 98%.
Reductions of up to 81% were maintained out to 150 days, according to a release from the developer of the drug, Silence Therapeutics.
High Lp(a) affects about one in five people worldwide and is a genetic risk factor for cardiovascular disease. There are no approved medications that selectively lower Lp(a), and levels cannot be significantly modified through lifestyle changes or any approved medications.
SLN360 is a siRNA that is designed to lower Lp(a) production by using the body’s natural process of RNA interference to target and silence messenger RNA transcribed from the LPA gene in liver cells.
The first-in-human APOLLO trial evaluated 32 patients with serum Lp(a) concentrations of at least 150 nmol/L and no cardiovascular disease who received a single subcutaneous dose of SLN360 (30 mg, 100 mg, less than or equal to 300 mg, or less than or equal to 600 mg) or placebo and were followed for up to 150 days.
No clinically important safety concerns were identified, although low-grade adverse events at the injection site occurred, most prominently at the highest dose, according to the company.
Study follow-up has been extended to 1 year. Patient enrollment continues in the multiple-ascending dose portion of the phase 1 study in patients with high Lp(a) and a confirmed history of stable atherosclerotic cardiovascular disease, the company statement notes.
Detailed results from APOLLO will be presented in a late-breaking clinical trials session at the American College of Cardiology Annual Scientific Session on April 3 by principal investigator Steven E. Nissen, MD, Cleveland Clinic.
A version of this article first appeared on Medscape.com.
‘Substantial’ CVD risks, burden up to a year after COVID-19
People who have had COVID-19 have an increased risk for, and 12-month burden of, cardiovascular disease (CVD) that is substantial and spans an array of cardiovascular disorders, a deep dive into federal data suggests.
“I went into this thinking that this is most likely happening in people to start with who have a higher risk of cardiovascular disorders, smokers, people with high BMI, diabetes, but what we found is something different,” Ziyad Al-Aly, MD, said in an interview. “It’s evident in people at high risk, but it was also as clear as the sun even in people who have no cardiovascular risk whatsoever.”
Rates were increased in younger adults, never smokers, White and Black people, and males and females, he said. “So the risk confirmed by the SARS-CoV-2 virus seems to spare almost no one.”
Although cardiovascular outcomes increased with the severity of the acute infection, the excess risks and burdens were also evident in those who never required hospitalization, a group that represents the majority of people with COVID-19, observed Dr. Al-Aly, who directs the Clinical Epidemiology Center at the Veterans Affairs St. Louis Health Care System.
“This study is very important because it underscores not just the acute cardiovascular risk associated with COVID but the increased risk of chronic cardiovascular outcomes as well,” cardiologist C. Michael Gibson, MD, professor of medicine, Harvard Medical School, Boston, said in an interview. “Given the number of patients in the U.S. who have been infected with COVID, this could represent a significant chronic burden on the health care system, particularly as health care professionals leave the profession.”
For the study, the investigators used national VA databases to build a cohort of 153,760 veterans who were alive 30 days after testing positive for COVID-19 between March 1, 2020, and January 2021. They were compared with a contemporary cohort of 5.6 million veterans with no evidence of SARS-CoV-2 infection and a historical cohort of 5.8 million veterans using the system in 2017 prior to the pandemic. Median follow-up was 347, 348, and 347 days, respectively.
As reported in Nature Medicine, the risk for a major adverse cardiovascular event, a composite of myocardial infarction, stroke, and all-cause mortality, was 4% higher in people who had been infected with COVID-19 than in those who had not.
“People say 4% is small, but actually it’s really, really big if you think about it in the context of the huge number of people who have had COVID-19 in the United States, and also globally,” Dr. Al-Aly said.
Compared with the contemporary control group, people who had COVID-19 had an increased risk (hazard ratio [HR]) and burden per 1,000 people at 1 year for the following cardiovascular outcomes:
- Stroke: HR, 1.52; burden, 4.03
- Transient ischemic attack: HR, 1.49; burden, 1.84
- Dysrhythmias: HR, 1.69; burden, 19.86
- Ischemic heart disease: HR, 1.66; burden, 7.28
- Heart failure: HR, 1.72; burden, 11.61
- Nonischemic cardiomyopathy: HR, 1.62; burden 3.56
- Pulmonary embolism: HR, 2.93; burden, 5.47
- Deep vein thrombosis: HR, 2.09; burden, 4.18
- Pericarditis: HR, 1.85, burden, 0.98
- Myocarditis: HR, 5.38; burden, 0.31
Recent reports have raised concerns about an association between COVID-19 vaccines and myocarditis and pericarditis, particularly in young males. Although very few of the participants were vaccinated prior to becoming infected, as vaccines were not yet widely available, the researchers performed two analyses censoring participants at the time of the first dose of any COVID-19 vaccine and adjusting for vaccination as a time-varying covariate.
The absolute numbers of myocarditis and pericarditis were still higher than the contemporary and historical cohorts. These numbers are much larger than those reported for myocarditis after vaccines, which are generally around 40 cases per 1 million people, observed Dr. Al-Aly.
The overall results were also consistent when compared with the historical control subjects.
“What we’re seeing in our report and others is that SARS-CoV-2 can leave a sort of scar or imprint on people, and some of these conditions are likely chronic conditions,” Dr. Al-Aly said. “So you’re going to have a generation of people who will bear the scar of COVID for their lifetime and I think that requires recognition and attention, so we’re aware of the magnitude of the problem and prepared to deal with it.”
With more than 76 million COVID-19 cases in the United States, that effort will likely have to be at the federal level, similar to President Joe Biden’s recent relaunch of the “Cancer Moonshot,” he added. “We need a greater and broader recognition at the federal level to try and recognize that when you have an earthquake, you don’t just deal with the earthquake when the earth is shaking, but you also need to deal with the aftermath.”
Dr. Gibson pointed out that this was a study of predominantly males and, thus, it’s unclear if the results can be extended to females. Nevertheless, he added, “long COVID may include outcomes beyond the central nervous system and we should educate patients about the risk of late cardiovascular outcomes.”
The authors noted the largely White, male cohort may limit generalizability of the findings. Other limitations include the possibility that some people may have had COVID-19 but were not tested, the datasets lacked information on cause of death, and possible residual confounding not accounted for in the adjusted analyses.
The research was funded by the U.S. Department of Veterans Affairs and two American Society of Nephrology and Kidney Cure fellowship awards. The authors declared no competing interests. Dr. Gibson reports having no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
People who have had COVID-19 have an increased risk for, and 12-month burden of, cardiovascular disease (CVD) that is substantial and spans an array of cardiovascular disorders, a deep dive into federal data suggests.
“I went into this thinking that this is most likely happening in people to start with who have a higher risk of cardiovascular disorders, smokers, people with high BMI, diabetes, but what we found is something different,” Ziyad Al-Aly, MD, said in an interview. “It’s evident in people at high risk, but it was also as clear as the sun even in people who have no cardiovascular risk whatsoever.”
Rates were increased in younger adults, never smokers, White and Black people, and males and females, he said. “So the risk confirmed by the SARS-CoV-2 virus seems to spare almost no one.”
Although cardiovascular outcomes increased with the severity of the acute infection, the excess risks and burdens were also evident in those who never required hospitalization, a group that represents the majority of people with COVID-19, observed Dr. Al-Aly, who directs the Clinical Epidemiology Center at the Veterans Affairs St. Louis Health Care System.
“This study is very important because it underscores not just the acute cardiovascular risk associated with COVID but the increased risk of chronic cardiovascular outcomes as well,” cardiologist C. Michael Gibson, MD, professor of medicine, Harvard Medical School, Boston, said in an interview. “Given the number of patients in the U.S. who have been infected with COVID, this could represent a significant chronic burden on the health care system, particularly as health care professionals leave the profession.”
For the study, the investigators used national VA databases to build a cohort of 153,760 veterans who were alive 30 days after testing positive for COVID-19 between March 1, 2020, and January 2021. They were compared with a contemporary cohort of 5.6 million veterans with no evidence of SARS-CoV-2 infection and a historical cohort of 5.8 million veterans using the system in 2017 prior to the pandemic. Median follow-up was 347, 348, and 347 days, respectively.
As reported in Nature Medicine, the risk for a major adverse cardiovascular event, a composite of myocardial infarction, stroke, and all-cause mortality, was 4% higher in people who had been infected with COVID-19 than in those who had not.
“People say 4% is small, but actually it’s really, really big if you think about it in the context of the huge number of people who have had COVID-19 in the United States, and also globally,” Dr. Al-Aly said.
Compared with the contemporary control group, people who had COVID-19 had an increased risk (hazard ratio [HR]) and burden per 1,000 people at 1 year for the following cardiovascular outcomes:
- Stroke: HR, 1.52; burden, 4.03
- Transient ischemic attack: HR, 1.49; burden, 1.84
- Dysrhythmias: HR, 1.69; burden, 19.86
- Ischemic heart disease: HR, 1.66; burden, 7.28
- Heart failure: HR, 1.72; burden, 11.61
- Nonischemic cardiomyopathy: HR, 1.62; burden 3.56
- Pulmonary embolism: HR, 2.93; burden, 5.47
- Deep vein thrombosis: HR, 2.09; burden, 4.18
- Pericarditis: HR, 1.85, burden, 0.98
- Myocarditis: HR, 5.38; burden, 0.31
Recent reports have raised concerns about an association between COVID-19 vaccines and myocarditis and pericarditis, particularly in young males. Although very few of the participants were vaccinated prior to becoming infected, as vaccines were not yet widely available, the researchers performed two analyses censoring participants at the time of the first dose of any COVID-19 vaccine and adjusting for vaccination as a time-varying covariate.
The absolute numbers of myocarditis and pericarditis were still higher than the contemporary and historical cohorts. These numbers are much larger than those reported for myocarditis after vaccines, which are generally around 40 cases per 1 million people, observed Dr. Al-Aly.
The overall results were also consistent when compared with the historical control subjects.
“What we’re seeing in our report and others is that SARS-CoV-2 can leave a sort of scar or imprint on people, and some of these conditions are likely chronic conditions,” Dr. Al-Aly said. “So you’re going to have a generation of people who will bear the scar of COVID for their lifetime and I think that requires recognition and attention, so we’re aware of the magnitude of the problem and prepared to deal with it.”
With more than 76 million COVID-19 cases in the United States, that effort will likely have to be at the federal level, similar to President Joe Biden’s recent relaunch of the “Cancer Moonshot,” he added. “We need a greater and broader recognition at the federal level to try and recognize that when you have an earthquake, you don’t just deal with the earthquake when the earth is shaking, but you also need to deal with the aftermath.”
Dr. Gibson pointed out that this was a study of predominantly males and, thus, it’s unclear if the results can be extended to females. Nevertheless, he added, “long COVID may include outcomes beyond the central nervous system and we should educate patients about the risk of late cardiovascular outcomes.”
The authors noted the largely White, male cohort may limit generalizability of the findings. Other limitations include the possibility that some people may have had COVID-19 but were not tested, the datasets lacked information on cause of death, and possible residual confounding not accounted for in the adjusted analyses.
The research was funded by the U.S. Department of Veterans Affairs and two American Society of Nephrology and Kidney Cure fellowship awards. The authors declared no competing interests. Dr. Gibson reports having no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
People who have had COVID-19 have an increased risk for, and 12-month burden of, cardiovascular disease (CVD) that is substantial and spans an array of cardiovascular disorders, a deep dive into federal data suggests.
“I went into this thinking that this is most likely happening in people to start with who have a higher risk of cardiovascular disorders, smokers, people with high BMI, diabetes, but what we found is something different,” Ziyad Al-Aly, MD, said in an interview. “It’s evident in people at high risk, but it was also as clear as the sun even in people who have no cardiovascular risk whatsoever.”
Rates were increased in younger adults, never smokers, White and Black people, and males and females, he said. “So the risk confirmed by the SARS-CoV-2 virus seems to spare almost no one.”
Although cardiovascular outcomes increased with the severity of the acute infection, the excess risks and burdens were also evident in those who never required hospitalization, a group that represents the majority of people with COVID-19, observed Dr. Al-Aly, who directs the Clinical Epidemiology Center at the Veterans Affairs St. Louis Health Care System.
“This study is very important because it underscores not just the acute cardiovascular risk associated with COVID but the increased risk of chronic cardiovascular outcomes as well,” cardiologist C. Michael Gibson, MD, professor of medicine, Harvard Medical School, Boston, said in an interview. “Given the number of patients in the U.S. who have been infected with COVID, this could represent a significant chronic burden on the health care system, particularly as health care professionals leave the profession.”
For the study, the investigators used national VA databases to build a cohort of 153,760 veterans who were alive 30 days after testing positive for COVID-19 between March 1, 2020, and January 2021. They were compared with a contemporary cohort of 5.6 million veterans with no evidence of SARS-CoV-2 infection and a historical cohort of 5.8 million veterans using the system in 2017 prior to the pandemic. Median follow-up was 347, 348, and 347 days, respectively.
As reported in Nature Medicine, the risk for a major adverse cardiovascular event, a composite of myocardial infarction, stroke, and all-cause mortality, was 4% higher in people who had been infected with COVID-19 than in those who had not.
“People say 4% is small, but actually it’s really, really big if you think about it in the context of the huge number of people who have had COVID-19 in the United States, and also globally,” Dr. Al-Aly said.
Compared with the contemporary control group, people who had COVID-19 had an increased risk (hazard ratio [HR]) and burden per 1,000 people at 1 year for the following cardiovascular outcomes:
- Stroke: HR, 1.52; burden, 4.03
- Transient ischemic attack: HR, 1.49; burden, 1.84
- Dysrhythmias: HR, 1.69; burden, 19.86
- Ischemic heart disease: HR, 1.66; burden, 7.28
- Heart failure: HR, 1.72; burden, 11.61
- Nonischemic cardiomyopathy: HR, 1.62; burden 3.56
- Pulmonary embolism: HR, 2.93; burden, 5.47
- Deep vein thrombosis: HR, 2.09; burden, 4.18
- Pericarditis: HR, 1.85, burden, 0.98
- Myocarditis: HR, 5.38; burden, 0.31
Recent reports have raised concerns about an association between COVID-19 vaccines and myocarditis and pericarditis, particularly in young males. Although very few of the participants were vaccinated prior to becoming infected, as vaccines were not yet widely available, the researchers performed two analyses censoring participants at the time of the first dose of any COVID-19 vaccine and adjusting for vaccination as a time-varying covariate.
The absolute numbers of myocarditis and pericarditis were still higher than the contemporary and historical cohorts. These numbers are much larger than those reported for myocarditis after vaccines, which are generally around 40 cases per 1 million people, observed Dr. Al-Aly.
The overall results were also consistent when compared with the historical control subjects.
“What we’re seeing in our report and others is that SARS-CoV-2 can leave a sort of scar or imprint on people, and some of these conditions are likely chronic conditions,” Dr. Al-Aly said. “So you’re going to have a generation of people who will bear the scar of COVID for their lifetime and I think that requires recognition and attention, so we’re aware of the magnitude of the problem and prepared to deal with it.”
With more than 76 million COVID-19 cases in the United States, that effort will likely have to be at the federal level, similar to President Joe Biden’s recent relaunch of the “Cancer Moonshot,” he added. “We need a greater and broader recognition at the federal level to try and recognize that when you have an earthquake, you don’t just deal with the earthquake when the earth is shaking, but you also need to deal with the aftermath.”
Dr. Gibson pointed out that this was a study of predominantly males and, thus, it’s unclear if the results can be extended to females. Nevertheless, he added, “long COVID may include outcomes beyond the central nervous system and we should educate patients about the risk of late cardiovascular outcomes.”
The authors noted the largely White, male cohort may limit generalizability of the findings. Other limitations include the possibility that some people may have had COVID-19 but were not tested, the datasets lacked information on cause of death, and possible residual confounding not accounted for in the adjusted analyses.
The research was funded by the U.S. Department of Veterans Affairs and two American Society of Nephrology and Kidney Cure fellowship awards. The authors declared no competing interests. Dr. Gibson reports having no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
Does endovascular therapy benefit strokes with larger ischemic cores?
The RESCUE-JAPAN LIMIT trial was presented at the International Stroke Conference by Shinichi Yoshimura, MD, Hyogo College of Medicine, Nishinomiya, Japan. The study was also published online in the New England Journal of Medicine to coincide with its presentation at the ISC meeting.
The trial showed that among patients with acute stroke and a large ischemic brain region, functional outcomes at 90 days were better with endovascular therapy and medical care than with medical care alone.
Patients who received endovascular therapy were more than twice as likely to have a good functional outcome, defined as a modified Rankin scale (mRS) score of 0-3 at 90 days, than those who received medical care alone.
While the rate of intracranial hemorrhage increased with endovascular therapy, authors of the study and outside commentators suggested that the benefit appeared to outweigh the risk. “Our results provide strong evidence that endovascular therapy improves patient outcomes when the infarct area is large,” Dr. Yoshimura concluded at the meeting, presented by the American Stroke Association, a division of the American Heart Association.
Commenting on the study at an ISC press conference, Tudor Jovin, MD, chair of neurology at Cooper University Hospital, Cherry Hill, New Jersey, said: “The question of strokes with a large core stroke being an exclusion criteria for endovascular therapy is arguably one of the hottest topics the field is facing at this time. There are several randomized trials ongoing aiming to answer this question.”
“The RESCUE-JAPAN trial is the first of these trials to report and shed some light on this issue,” Dr. Jovin added. “The results appear to show that these patients with large core infarcts have just as much benefit from endovascular therapy as patients with smaller infarcts.”
Dr. Jovin described these findings as encouraging but also surprising. “When these large core randomized trials were planned, there was a belief that there would be benefit at some level. But what is surprising to me is that in this trial the benefit was similar to that seen in trials in patients with moderate or small core infarcts. This begs the question of whether we should care about the size of the infarct when we are considering taking these patients for thrombectomy,” he said.
Confirmation needed
On whether this will change practice, Dr. Jovin cautioned that this was just one study with a relatively small number of patients. “I think it is important that all the other randomized trials ongoing should continue so that we have a definitive answer to this question,” he said.
In his presentation, Dr. Yoshimura explained that current guidelines recommended endovascular therapy for patients with large cerebral vessel occlusion and a small or moderate infarct size – an ASPECTS score (Alberta Stroke Program Early Computed Tomographic Score) of 6 or higher. The ASPECTS score has a scale of 1-10, with lower values indicating larger infarction.
The RESCUE-JAPAN LIMIT study included 203 patients with occlusion of large cerebral vessels and sizable strokes on imaging, as indicated by an ASPECTS score of 3 to 5.
Patients were randomly assigned to receive endovascular therapy with medical care (endovascular-therapy group) or medical therapy alone (medical-care group) within 6 hours after they were last known to be well or within 24 hours if there was no early change on fluid-attenuated inversion recovery images indicating that the infarction was recent.
The percentage of patients with a good outcome as defined by an mRS score of 0 to 3 at 90 days, the primary outcome, was 31.0% in the endovascular-therapy group and 12.7% in the medical-care group (relative risk, 2.43; 95% confidence interval, 1.35 to 4.37; P = .002).
Secondary outcomes were mRS scores of 0 to 2 and 0 to 1, an ordinal shift across the range of mRS scores toward a better outcome at 90 days, and an improvement of at least 8 points in the National Institutes of Health Stroke Scale (NIHSS) score (range, 0 to 42, with higher scores indicating greater deficit) at 48 hours.
An mRS score of 0 to 2 was seen in 14% of patients in the endovascular-therapy group and 6.9% in the medical-care group (RR, 2.04; 95% CI, 0.86 to 4.84), and an mRS score of 0 to 1 was reported in 5% of the endovascular group versus 2.9% of the medical group (RR, 1.70; 95% CI, 0.42 to 6.93).
The ordinal shift across the range of mRS scores also favored endovascular therapy (common odds ratio, 2.42; 95% CI, 1.46 to 4.01).
An improvement of at least 8 points on the NIHSS score at 48 hours was observed in 31.0% of the patients in the endovascular-therapy group and 8.8% of those in the medical-care group (RR, 3.51; 95% CI, 1.76 to 7.00).
In terms of safety, any intracranial hemorrhage occurred in 58.0% of patients in the endovascular group and 31.4% of those in the medical therapy group (RR, 1.85; 95% CI, 1.33 to 2.58; P < .001).
There was also a trend toward an increase in symptomatic intracranial hemorrhage in the endovascular group (9% vs. 4.9%), but this did not reach significance (RR, 1.84; 95% CI, 0.64 to 5.29; P = .25).
In the NEJM paper, the authors pointed out that the ASPECTS value in most of the patients in this study was determined with the use of diffusion-weighted MRI, as MRI is widely used in Japan for the diagnosis of acute ischemic stroke. They noted that differences between ASPECTS values based on CT results and those based on diffusion-weighted MRI results should be considered in the interpretation of the results and that previous studies have suggested that an ASPECTS value determined with the use of diffusion-weighted MRI may be one level lower than that determined with the use of CT.
They also noted that there was a relatively low use of thrombolysis in the trial (27% to 29%), which may have altered the outcomes in both groups and disadvantaged the medical-care group. However, they add that most guidelines recommend against the use of thrombolysis when there is extensive ischemic change on imaging.
Risk/benefit trade-off
Commenting on the trade-off between benefits and risks in the study, Dr. Jovin said the increase in intracranial hemorrhage seen in the endovascular group was similar to that seen in other situations.
“This is not really any different from what is seen when giving tPA [tissue plasminogen activator] to stroke patients or when performing thrombectomy in small or moderate core strokes – we know that intracranial hemorrhage is the price to pay,” he stated.
“While the increase in symptomatic intracranial hemorrhage was nonsignificant, the trend is very clear, and I believe it is real,” Dr. Jovin said. “But I think what matters – and what matters to patients – is that there is a much higher chance of having a good outcome with endovascular therapy. I think most patients will accept the extra risk of intracranial hemorrhage if there is an even higher chance of having a better neurological outcome. This is no different to the approach that we take when we treat patients with IV tPA.”
Dr. Jovin pointed out that the RESCUE-JAPAN study did not include the largest core infarcts (ASPECTS score 0-1), but he added that these very large core infarcts are quite rare – especially in patients in the early time window.
He concluded that the study provided important information but cautioned that, with just 200 patients, the findings needed confirmation from other randomized trials that are ongoing.
Also speaking at the 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 previous trials had established endovascular therapy for patients with large cerebral artery occlusions who have primarily preserved brain tissue and small infarct cores.
“We have picked off the low-lying fruit – the patients with small areas of infarcted brain. But perhaps most patients do not fit into this category and now we are seeing trials addressing these groups,” he said. “This initial study suggests that these patients with larger core infarcts can indeed still benefit from this therapy tremendously.”
The RESCUE-JAPAN LIMIT study was supported in part by the Mihara Cerebrovascular Disorder Research Promotion Fund and the Japanese Society for Neuroendovascular Therapy. There was no industry involvement. Dr. Yoshimura reported research grants from Stryker, Siemens Healthineers, Bristol-Myers Squibb, Sanofi, Eisai, Daiichi Sankyo, Teijin Pharma, Chugai Pharmaceutical, HEALIOS, Asahi Kasei Medical, Kowa, and CSL Behring; and lecturer fees from Stryker, Medtronic, Johnson & Johnson, Kaneka, Terumo, Biomedical Solutions, Boehringer-Ingelheim, Daiichi Sankyo, Bayer, and Bristol-Meyers Squibb.
A version of this article first appeared on Medscape.com.
The RESCUE-JAPAN LIMIT trial was presented at the International Stroke Conference by Shinichi Yoshimura, MD, Hyogo College of Medicine, Nishinomiya, Japan. The study was also published online in the New England Journal of Medicine to coincide with its presentation at the ISC meeting.
The trial showed that among patients with acute stroke and a large ischemic brain region, functional outcomes at 90 days were better with endovascular therapy and medical care than with medical care alone.
Patients who received endovascular therapy were more than twice as likely to have a good functional outcome, defined as a modified Rankin scale (mRS) score of 0-3 at 90 days, than those who received medical care alone.
While the rate of intracranial hemorrhage increased with endovascular therapy, authors of the study and outside commentators suggested that the benefit appeared to outweigh the risk. “Our results provide strong evidence that endovascular therapy improves patient outcomes when the infarct area is large,” Dr. Yoshimura concluded at the meeting, presented by the American Stroke Association, a division of the American Heart Association.
Commenting on the study at an ISC press conference, Tudor Jovin, MD, chair of neurology at Cooper University Hospital, Cherry Hill, New Jersey, said: “The question of strokes with a large core stroke being an exclusion criteria for endovascular therapy is arguably one of the hottest topics the field is facing at this time. There are several randomized trials ongoing aiming to answer this question.”
“The RESCUE-JAPAN trial is the first of these trials to report and shed some light on this issue,” Dr. Jovin added. “The results appear to show that these patients with large core infarcts have just as much benefit from endovascular therapy as patients with smaller infarcts.”
Dr. Jovin described these findings as encouraging but also surprising. “When these large core randomized trials were planned, there was a belief that there would be benefit at some level. But what is surprising to me is that in this trial the benefit was similar to that seen in trials in patients with moderate or small core infarcts. This begs the question of whether we should care about the size of the infarct when we are considering taking these patients for thrombectomy,” he said.
Confirmation needed
On whether this will change practice, Dr. Jovin cautioned that this was just one study with a relatively small number of patients. “I think it is important that all the other randomized trials ongoing should continue so that we have a definitive answer to this question,” he said.
In his presentation, Dr. Yoshimura explained that current guidelines recommended endovascular therapy for patients with large cerebral vessel occlusion and a small or moderate infarct size – an ASPECTS score (Alberta Stroke Program Early Computed Tomographic Score) of 6 or higher. The ASPECTS score has a scale of 1-10, with lower values indicating larger infarction.
The RESCUE-JAPAN LIMIT study included 203 patients with occlusion of large cerebral vessels and sizable strokes on imaging, as indicated by an ASPECTS score of 3 to 5.
Patients were randomly assigned to receive endovascular therapy with medical care (endovascular-therapy group) or medical therapy alone (medical-care group) within 6 hours after they were last known to be well or within 24 hours if there was no early change on fluid-attenuated inversion recovery images indicating that the infarction was recent.
The percentage of patients with a good outcome as defined by an mRS score of 0 to 3 at 90 days, the primary outcome, was 31.0% in the endovascular-therapy group and 12.7% in the medical-care group (relative risk, 2.43; 95% confidence interval, 1.35 to 4.37; P = .002).
Secondary outcomes were mRS scores of 0 to 2 and 0 to 1, an ordinal shift across the range of mRS scores toward a better outcome at 90 days, and an improvement of at least 8 points in the National Institutes of Health Stroke Scale (NIHSS) score (range, 0 to 42, with higher scores indicating greater deficit) at 48 hours.
An mRS score of 0 to 2 was seen in 14% of patients in the endovascular-therapy group and 6.9% in the medical-care group (RR, 2.04; 95% CI, 0.86 to 4.84), and an mRS score of 0 to 1 was reported in 5% of the endovascular group versus 2.9% of the medical group (RR, 1.70; 95% CI, 0.42 to 6.93).
The ordinal shift across the range of mRS scores also favored endovascular therapy (common odds ratio, 2.42; 95% CI, 1.46 to 4.01).
An improvement of at least 8 points on the NIHSS score at 48 hours was observed in 31.0% of the patients in the endovascular-therapy group and 8.8% of those in the medical-care group (RR, 3.51; 95% CI, 1.76 to 7.00).
In terms of safety, any intracranial hemorrhage occurred in 58.0% of patients in the endovascular group and 31.4% of those in the medical therapy group (RR, 1.85; 95% CI, 1.33 to 2.58; P < .001).
There was also a trend toward an increase in symptomatic intracranial hemorrhage in the endovascular group (9% vs. 4.9%), but this did not reach significance (RR, 1.84; 95% CI, 0.64 to 5.29; P = .25).
In the NEJM paper, the authors pointed out that the ASPECTS value in most of the patients in this study was determined with the use of diffusion-weighted MRI, as MRI is widely used in Japan for the diagnosis of acute ischemic stroke. They noted that differences between ASPECTS values based on CT results and those based on diffusion-weighted MRI results should be considered in the interpretation of the results and that previous studies have suggested that an ASPECTS value determined with the use of diffusion-weighted MRI may be one level lower than that determined with the use of CT.
They also noted that there was a relatively low use of thrombolysis in the trial (27% to 29%), which may have altered the outcomes in both groups and disadvantaged the medical-care group. However, they add that most guidelines recommend against the use of thrombolysis when there is extensive ischemic change on imaging.
Risk/benefit trade-off
Commenting on the trade-off between benefits and risks in the study, Dr. Jovin said the increase in intracranial hemorrhage seen in the endovascular group was similar to that seen in other situations.
“This is not really any different from what is seen when giving tPA [tissue plasminogen activator] to stroke patients or when performing thrombectomy in small or moderate core strokes – we know that intracranial hemorrhage is the price to pay,” he stated.
“While the increase in symptomatic intracranial hemorrhage was nonsignificant, the trend is very clear, and I believe it is real,” Dr. Jovin said. “But I think what matters – and what matters to patients – is that there is a much higher chance of having a good outcome with endovascular therapy. I think most patients will accept the extra risk of intracranial hemorrhage if there is an even higher chance of having a better neurological outcome. This is no different to the approach that we take when we treat patients with IV tPA.”
Dr. Jovin pointed out that the RESCUE-JAPAN study did not include the largest core infarcts (ASPECTS score 0-1), but he added that these very large core infarcts are quite rare – especially in patients in the early time window.
He concluded that the study provided important information but cautioned that, with just 200 patients, the findings needed confirmation from other randomized trials that are ongoing.
Also speaking at the 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 previous trials had established endovascular therapy for patients with large cerebral artery occlusions who have primarily preserved brain tissue and small infarct cores.
“We have picked off the low-lying fruit – the patients with small areas of infarcted brain. But perhaps most patients do not fit into this category and now we are seeing trials addressing these groups,” he said. “This initial study suggests that these patients with larger core infarcts can indeed still benefit from this therapy tremendously.”
The RESCUE-JAPAN LIMIT study was supported in part by the Mihara Cerebrovascular Disorder Research Promotion Fund and the Japanese Society for Neuroendovascular Therapy. There was no industry involvement. Dr. Yoshimura reported research grants from Stryker, Siemens Healthineers, Bristol-Myers Squibb, Sanofi, Eisai, Daiichi Sankyo, Teijin Pharma, Chugai Pharmaceutical, HEALIOS, Asahi Kasei Medical, Kowa, and CSL Behring; and lecturer fees from Stryker, Medtronic, Johnson & Johnson, Kaneka, Terumo, Biomedical Solutions, Boehringer-Ingelheim, Daiichi Sankyo, Bayer, and Bristol-Meyers Squibb.
A version of this article first appeared on Medscape.com.
The RESCUE-JAPAN LIMIT trial was presented at the International Stroke Conference by Shinichi Yoshimura, MD, Hyogo College of Medicine, Nishinomiya, Japan. The study was also published online in the New England Journal of Medicine to coincide with its presentation at the ISC meeting.
The trial showed that among patients with acute stroke and a large ischemic brain region, functional outcomes at 90 days were better with endovascular therapy and medical care than with medical care alone.
Patients who received endovascular therapy were more than twice as likely to have a good functional outcome, defined as a modified Rankin scale (mRS) score of 0-3 at 90 days, than those who received medical care alone.
While the rate of intracranial hemorrhage increased with endovascular therapy, authors of the study and outside commentators suggested that the benefit appeared to outweigh the risk. “Our results provide strong evidence that endovascular therapy improves patient outcomes when the infarct area is large,” Dr. Yoshimura concluded at the meeting, presented by the American Stroke Association, a division of the American Heart Association.
Commenting on the study at an ISC press conference, Tudor Jovin, MD, chair of neurology at Cooper University Hospital, Cherry Hill, New Jersey, said: “The question of strokes with a large core stroke being an exclusion criteria for endovascular therapy is arguably one of the hottest topics the field is facing at this time. There are several randomized trials ongoing aiming to answer this question.”
“The RESCUE-JAPAN trial is the first of these trials to report and shed some light on this issue,” Dr. Jovin added. “The results appear to show that these patients with large core infarcts have just as much benefit from endovascular therapy as patients with smaller infarcts.”
Dr. Jovin described these findings as encouraging but also surprising. “When these large core randomized trials were planned, there was a belief that there would be benefit at some level. But what is surprising to me is that in this trial the benefit was similar to that seen in trials in patients with moderate or small core infarcts. This begs the question of whether we should care about the size of the infarct when we are considering taking these patients for thrombectomy,” he said.
Confirmation needed
On whether this will change practice, Dr. Jovin cautioned that this was just one study with a relatively small number of patients. “I think it is important that all the other randomized trials ongoing should continue so that we have a definitive answer to this question,” he said.
In his presentation, Dr. Yoshimura explained that current guidelines recommended endovascular therapy for patients with large cerebral vessel occlusion and a small or moderate infarct size – an ASPECTS score (Alberta Stroke Program Early Computed Tomographic Score) of 6 or higher. The ASPECTS score has a scale of 1-10, with lower values indicating larger infarction.
The RESCUE-JAPAN LIMIT study included 203 patients with occlusion of large cerebral vessels and sizable strokes on imaging, as indicated by an ASPECTS score of 3 to 5.
Patients were randomly assigned to receive endovascular therapy with medical care (endovascular-therapy group) or medical therapy alone (medical-care group) within 6 hours after they were last known to be well or within 24 hours if there was no early change on fluid-attenuated inversion recovery images indicating that the infarction was recent.
The percentage of patients with a good outcome as defined by an mRS score of 0 to 3 at 90 days, the primary outcome, was 31.0% in the endovascular-therapy group and 12.7% in the medical-care group (relative risk, 2.43; 95% confidence interval, 1.35 to 4.37; P = .002).
Secondary outcomes were mRS scores of 0 to 2 and 0 to 1, an ordinal shift across the range of mRS scores toward a better outcome at 90 days, and an improvement of at least 8 points in the National Institutes of Health Stroke Scale (NIHSS) score (range, 0 to 42, with higher scores indicating greater deficit) at 48 hours.
An mRS score of 0 to 2 was seen in 14% of patients in the endovascular-therapy group and 6.9% in the medical-care group (RR, 2.04; 95% CI, 0.86 to 4.84), and an mRS score of 0 to 1 was reported in 5% of the endovascular group versus 2.9% of the medical group (RR, 1.70; 95% CI, 0.42 to 6.93).
The ordinal shift across the range of mRS scores also favored endovascular therapy (common odds ratio, 2.42; 95% CI, 1.46 to 4.01).
An improvement of at least 8 points on the NIHSS score at 48 hours was observed in 31.0% of the patients in the endovascular-therapy group and 8.8% of those in the medical-care group (RR, 3.51; 95% CI, 1.76 to 7.00).
In terms of safety, any intracranial hemorrhage occurred in 58.0% of patients in the endovascular group and 31.4% of those in the medical therapy group (RR, 1.85; 95% CI, 1.33 to 2.58; P < .001).
There was also a trend toward an increase in symptomatic intracranial hemorrhage in the endovascular group (9% vs. 4.9%), but this did not reach significance (RR, 1.84; 95% CI, 0.64 to 5.29; P = .25).
In the NEJM paper, the authors pointed out that the ASPECTS value in most of the patients in this study was determined with the use of diffusion-weighted MRI, as MRI is widely used in Japan for the diagnosis of acute ischemic stroke. They noted that differences between ASPECTS values based on CT results and those based on diffusion-weighted MRI results should be considered in the interpretation of the results and that previous studies have suggested that an ASPECTS value determined with the use of diffusion-weighted MRI may be one level lower than that determined with the use of CT.
They also noted that there was a relatively low use of thrombolysis in the trial (27% to 29%), which may have altered the outcomes in both groups and disadvantaged the medical-care group. However, they add that most guidelines recommend against the use of thrombolysis when there is extensive ischemic change on imaging.
Risk/benefit trade-off
Commenting on the trade-off between benefits and risks in the study, Dr. Jovin said the increase in intracranial hemorrhage seen in the endovascular group was similar to that seen in other situations.
“This is not really any different from what is seen when giving tPA [tissue plasminogen activator] to stroke patients or when performing thrombectomy in small or moderate core strokes – we know that intracranial hemorrhage is the price to pay,” he stated.
“While the increase in symptomatic intracranial hemorrhage was nonsignificant, the trend is very clear, and I believe it is real,” Dr. Jovin said. “But I think what matters – and what matters to patients – is that there is a much higher chance of having a good outcome with endovascular therapy. I think most patients will accept the extra risk of intracranial hemorrhage if there is an even higher chance of having a better neurological outcome. This is no different to the approach that we take when we treat patients with IV tPA.”
Dr. Jovin pointed out that the RESCUE-JAPAN study did not include the largest core infarcts (ASPECTS score 0-1), but he added that these very large core infarcts are quite rare – especially in patients in the early time window.
He concluded that the study provided important information but cautioned that, with just 200 patients, the findings needed confirmation from other randomized trials that are ongoing.
Also speaking at the 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 previous trials had established endovascular therapy for patients with large cerebral artery occlusions who have primarily preserved brain tissue and small infarct cores.
“We have picked off the low-lying fruit – the patients with small areas of infarcted brain. But perhaps most patients do not fit into this category and now we are seeing trials addressing these groups,” he said. “This initial study suggests that these patients with larger core infarcts can indeed still benefit from this therapy tremendously.”
The RESCUE-JAPAN LIMIT study was supported in part by the Mihara Cerebrovascular Disorder Research Promotion Fund and the Japanese Society for Neuroendovascular Therapy. There was no industry involvement. Dr. Yoshimura reported research grants from Stryker, Siemens Healthineers, Bristol-Myers Squibb, Sanofi, Eisai, Daiichi Sankyo, Teijin Pharma, Chugai Pharmaceutical, HEALIOS, Asahi Kasei Medical, Kowa, and CSL Behring; and lecturer fees from Stryker, Medtronic, Johnson & Johnson, Kaneka, Terumo, Biomedical Solutions, Boehringer-Ingelheim, Daiichi Sankyo, Bayer, and Bristol-Meyers Squibb.
A version of this article first appeared on Medscape.com.
FROM ISC 2022
Chronic marijuana use linked to recurrent stroke
, new observational research suggests. “Our analysis shows young marijuana users with a history of stroke or transient ischemic attack remain at significantly high risk for future strokes,” said lead study author Akhil Jain, MD, a resident physician at Mercy Fitzgerald Hospital in Darby, Pennsylvania.
“It’s essential to raise awareness among young adults about the impact of chronic habitual use of marijuana, especially if they have established cardiovascular risk factors or previous stroke.”
The study will be presented during the International Stroke Conference, presented by the American Stroke Association, a division of the American Heart Association.
An increasing number of jurisdictions are allowing marijuana use. To date, 18 states and the District of Columbia have legalized recreational cannabis use, the investigators noted.
Research suggests cannabis use disorder – defined as the chronic habitual use of cannabis – is more prevalent in the young adult population. But Dr. Jain said the population of marijuana users is “a changing dynamic.”
Cannabis use has been linked to an increased risk for first-time stroke or transient ischemic attack (TIA). Traditional stroke risk factors include hypertension, diabetes, and diseases related to blood vessels or blood circulation, including atherosclerosis.
Young adults might have additional stroke risk factors, such as behavioral habits like substance abuse, low physical activity, and smoking, oral contraceptives use among females, and brain infections, especially in the immunocompromised, said Dr. Jain.
Research from the American Heart Association shows stroke rates are increasing among adults 18 to 45 years of age. Each year, young adults account for up to 15% of strokes in the United States.
Prevalence and risk for recurrent stroke in patients with previous stroke or TIA in cannabis users have not been clearly established, the researchers pointed out.
A higher rate of recurrent stroke
For this new study, Dr. Jain and colleagues used data from the National Inpatient Sample from October 2015 to December 2017. They identified hospitalizations among young adults 18 to 45 years of age with a previous history of stroke or TIA.
They then grouped these patients into those with cannabis use disorder (4,690) and those without cannabis use disorder (156,700). The median age in both cohorts was 37 years.
The analysis did not include those who were considered in remission from cannabis use disorder.
Results showed that 6.9% of those with cannabis use disorder were hospitalized for a recurrent stroke, compared with 5.4% of those without cannabis use disorder (P < .001).
After adjustment for demographic factors (age, sex, race, household income), and pre-existing conditions, patients with cannabis use disorder were 48% more likely to be hospitalized for recurrent stroke than those without cannabis use disorder (odds ratio, 1.48; 95% confidence interval, 1.28-1.71; P < .001).
Compared with the group without cannabis use disorder, the cannabis use disorder group had more men (55.2% vs. 40.2%), more African American people (44.6% vs. 37.2%), and more use of tobacco (73.9% vs. 39.6%) and alcohol (16.5% vs. 3.6%). They also had a greater percentage of chronic obstructive pulmonary disease, depression, and psychoses.
But a smaller percentage of those with cannabis use disorder had hypertension (51.3% vs. 55.6%; P = .001) and diabetes (16.3% vs. 22.7%; P < .001), which is an “interesting” finding, said Dr. Jain.
“We observed that even with a lower rate of cardiovascular risk factors, after controlling for all the risk factors, we still found the cannabis users had a higher rate of recurrent stroke.”
He noted this was a retrospective study without a control group. “If both groups had comparable hypertension, then this risk might actually be more evident,” said Dr. Jain. “We need a prospective study with comparable groups.”
Living in low-income neighborhoods and in northeast and southern regions of the United States was also more common in the cannabis use disorder group.
Hypothesis-generating research
The study did not investigate the possible mechanisms by which marijuana use might increase stroke risk, but Dr. Jain speculated that these could include factors such as impaired blood vessel function, changes in blood supply, an increased tendency of blood clotting, impaired energy production in brain cells, and an imbalance between molecules that harm healthy tissue and the antioxidant defenses that neutralize them.
As cannabis use may pose a different risk for a new stroke, as opposed a previous stroke, Dr. Jain said it would be interesting to study the amount of “residual function deficit” experienced with the first stroke.
The new study represents “foundational research” upon which other research teams can build, said Dr. Jain. “Our study is hypothesis-generating research for a future prospective randomized controlled trial.”
A limitation of the study is that it did not consider the effect of various doses, duration, and forms of cannabis abuse, or use of medicinal cannabis or other drugs.
Robert L. Page II, PharmD, professor, departments of clinical pharmacy and physical medicine/rehabilitation, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, provided a comment on this new research.
A cannabis use disorder diagnosis provides “specific criteria” with regard to chronicity of use and reflects “more of a physical and psychological dependence upon cannabis,” said Dr. Page, who chaired the writing group for the AHA 2020 cannabis and cardiovascular disease scientific statement.
He explained what sets people with cannabis use disorder apart from “run-of-the-mill” recreational cannabis users is that “these are individuals who use a cannabis product, whether it’s smoking it, vaping it, or consuming it via an edible, and are using it on a regular basis, in a chronic fashion.”
The study received no outside funding. The authors report no relevant disclosures.
A version of this article first appeared on Medscape.com.
, new observational research suggests. “Our analysis shows young marijuana users with a history of stroke or transient ischemic attack remain at significantly high risk for future strokes,” said lead study author Akhil Jain, MD, a resident physician at Mercy Fitzgerald Hospital in Darby, Pennsylvania.
“It’s essential to raise awareness among young adults about the impact of chronic habitual use of marijuana, especially if they have established cardiovascular risk factors or previous stroke.”
The study will be presented during the International Stroke Conference, presented by the American Stroke Association, a division of the American Heart Association.
An increasing number of jurisdictions are allowing marijuana use. To date, 18 states and the District of Columbia have legalized recreational cannabis use, the investigators noted.
Research suggests cannabis use disorder – defined as the chronic habitual use of cannabis – is more prevalent in the young adult population. But Dr. Jain said the population of marijuana users is “a changing dynamic.”
Cannabis use has been linked to an increased risk for first-time stroke or transient ischemic attack (TIA). Traditional stroke risk factors include hypertension, diabetes, and diseases related to blood vessels or blood circulation, including atherosclerosis.
Young adults might have additional stroke risk factors, such as behavioral habits like substance abuse, low physical activity, and smoking, oral contraceptives use among females, and brain infections, especially in the immunocompromised, said Dr. Jain.
Research from the American Heart Association shows stroke rates are increasing among adults 18 to 45 years of age. Each year, young adults account for up to 15% of strokes in the United States.
Prevalence and risk for recurrent stroke in patients with previous stroke or TIA in cannabis users have not been clearly established, the researchers pointed out.
A higher rate of recurrent stroke
For this new study, Dr. Jain and colleagues used data from the National Inpatient Sample from October 2015 to December 2017. They identified hospitalizations among young adults 18 to 45 years of age with a previous history of stroke or TIA.
They then grouped these patients into those with cannabis use disorder (4,690) and those without cannabis use disorder (156,700). The median age in both cohorts was 37 years.
The analysis did not include those who were considered in remission from cannabis use disorder.
Results showed that 6.9% of those with cannabis use disorder were hospitalized for a recurrent stroke, compared with 5.4% of those without cannabis use disorder (P < .001).
After adjustment for demographic factors (age, sex, race, household income), and pre-existing conditions, patients with cannabis use disorder were 48% more likely to be hospitalized for recurrent stroke than those without cannabis use disorder (odds ratio, 1.48; 95% confidence interval, 1.28-1.71; P < .001).
Compared with the group without cannabis use disorder, the cannabis use disorder group had more men (55.2% vs. 40.2%), more African American people (44.6% vs. 37.2%), and more use of tobacco (73.9% vs. 39.6%) and alcohol (16.5% vs. 3.6%). They also had a greater percentage of chronic obstructive pulmonary disease, depression, and psychoses.
But a smaller percentage of those with cannabis use disorder had hypertension (51.3% vs. 55.6%; P = .001) and diabetes (16.3% vs. 22.7%; P < .001), which is an “interesting” finding, said Dr. Jain.
“We observed that even with a lower rate of cardiovascular risk factors, after controlling for all the risk factors, we still found the cannabis users had a higher rate of recurrent stroke.”
He noted this was a retrospective study without a control group. “If both groups had comparable hypertension, then this risk might actually be more evident,” said Dr. Jain. “We need a prospective study with comparable groups.”
Living in low-income neighborhoods and in northeast and southern regions of the United States was also more common in the cannabis use disorder group.
Hypothesis-generating research
The study did not investigate the possible mechanisms by which marijuana use might increase stroke risk, but Dr. Jain speculated that these could include factors such as impaired blood vessel function, changes in blood supply, an increased tendency of blood clotting, impaired energy production in brain cells, and an imbalance between molecules that harm healthy tissue and the antioxidant defenses that neutralize them.
As cannabis use may pose a different risk for a new stroke, as opposed a previous stroke, Dr. Jain said it would be interesting to study the amount of “residual function deficit” experienced with the first stroke.
The new study represents “foundational research” upon which other research teams can build, said Dr. Jain. “Our study is hypothesis-generating research for a future prospective randomized controlled trial.”
A limitation of the study is that it did not consider the effect of various doses, duration, and forms of cannabis abuse, or use of medicinal cannabis or other drugs.
Robert L. Page II, PharmD, professor, departments of clinical pharmacy and physical medicine/rehabilitation, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, provided a comment on this new research.
A cannabis use disorder diagnosis provides “specific criteria” with regard to chronicity of use and reflects “more of a physical and psychological dependence upon cannabis,” said Dr. Page, who chaired the writing group for the AHA 2020 cannabis and cardiovascular disease scientific statement.
He explained what sets people with cannabis use disorder apart from “run-of-the-mill” recreational cannabis users is that “these are individuals who use a cannabis product, whether it’s smoking it, vaping it, or consuming it via an edible, and are using it on a regular basis, in a chronic fashion.”
The study received no outside funding. The authors report no relevant disclosures.
A version of this article first appeared on Medscape.com.
, new observational research suggests. “Our analysis shows young marijuana users with a history of stroke or transient ischemic attack remain at significantly high risk for future strokes,” said lead study author Akhil Jain, MD, a resident physician at Mercy Fitzgerald Hospital in Darby, Pennsylvania.
“It’s essential to raise awareness among young adults about the impact of chronic habitual use of marijuana, especially if they have established cardiovascular risk factors or previous stroke.”
The study will be presented during the International Stroke Conference, presented by the American Stroke Association, a division of the American Heart Association.
An increasing number of jurisdictions are allowing marijuana use. To date, 18 states and the District of Columbia have legalized recreational cannabis use, the investigators noted.
Research suggests cannabis use disorder – defined as the chronic habitual use of cannabis – is more prevalent in the young adult population. But Dr. Jain said the population of marijuana users is “a changing dynamic.”
Cannabis use has been linked to an increased risk for first-time stroke or transient ischemic attack (TIA). Traditional stroke risk factors include hypertension, diabetes, and diseases related to blood vessels or blood circulation, including atherosclerosis.
Young adults might have additional stroke risk factors, such as behavioral habits like substance abuse, low physical activity, and smoking, oral contraceptives use among females, and brain infections, especially in the immunocompromised, said Dr. Jain.
Research from the American Heart Association shows stroke rates are increasing among adults 18 to 45 years of age. Each year, young adults account for up to 15% of strokes in the United States.
Prevalence and risk for recurrent stroke in patients with previous stroke or TIA in cannabis users have not been clearly established, the researchers pointed out.
A higher rate of recurrent stroke
For this new study, Dr. Jain and colleagues used data from the National Inpatient Sample from October 2015 to December 2017. They identified hospitalizations among young adults 18 to 45 years of age with a previous history of stroke or TIA.
They then grouped these patients into those with cannabis use disorder (4,690) and those without cannabis use disorder (156,700). The median age in both cohorts was 37 years.
The analysis did not include those who were considered in remission from cannabis use disorder.
Results showed that 6.9% of those with cannabis use disorder were hospitalized for a recurrent stroke, compared with 5.4% of those without cannabis use disorder (P < .001).
After adjustment for demographic factors (age, sex, race, household income), and pre-existing conditions, patients with cannabis use disorder were 48% more likely to be hospitalized for recurrent stroke than those without cannabis use disorder (odds ratio, 1.48; 95% confidence interval, 1.28-1.71; P < .001).
Compared with the group without cannabis use disorder, the cannabis use disorder group had more men (55.2% vs. 40.2%), more African American people (44.6% vs. 37.2%), and more use of tobacco (73.9% vs. 39.6%) and alcohol (16.5% vs. 3.6%). They also had a greater percentage of chronic obstructive pulmonary disease, depression, and psychoses.
But a smaller percentage of those with cannabis use disorder had hypertension (51.3% vs. 55.6%; P = .001) and diabetes (16.3% vs. 22.7%; P < .001), which is an “interesting” finding, said Dr. Jain.
“We observed that even with a lower rate of cardiovascular risk factors, after controlling for all the risk factors, we still found the cannabis users had a higher rate of recurrent stroke.”
He noted this was a retrospective study without a control group. “If both groups had comparable hypertension, then this risk might actually be more evident,” said Dr. Jain. “We need a prospective study with comparable groups.”
Living in low-income neighborhoods and in northeast and southern regions of the United States was also more common in the cannabis use disorder group.
Hypothesis-generating research
The study did not investigate the possible mechanisms by which marijuana use might increase stroke risk, but Dr. Jain speculated that these could include factors such as impaired blood vessel function, changes in blood supply, an increased tendency of blood clotting, impaired energy production in brain cells, and an imbalance between molecules that harm healthy tissue and the antioxidant defenses that neutralize them.
As cannabis use may pose a different risk for a new stroke, as opposed a previous stroke, Dr. Jain said it would be interesting to study the amount of “residual function deficit” experienced with the first stroke.
The new study represents “foundational research” upon which other research teams can build, said Dr. Jain. “Our study is hypothesis-generating research for a future prospective randomized controlled trial.”
A limitation of the study is that it did not consider the effect of various doses, duration, and forms of cannabis abuse, or use of medicinal cannabis or other drugs.
Robert L. Page II, PharmD, professor, departments of clinical pharmacy and physical medicine/rehabilitation, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, provided a comment on this new research.
A cannabis use disorder diagnosis provides “specific criteria” with regard to chronicity of use and reflects “more of a physical and psychological dependence upon cannabis,” said Dr. Page, who chaired the writing group for the AHA 2020 cannabis and cardiovascular disease scientific statement.
He explained what sets people with cannabis use disorder apart from “run-of-the-mill” recreational cannabis users is that “these are individuals who use a cannabis product, whether it’s smoking it, vaping it, or consuming it via an edible, and are using it on a regular basis, in a chronic fashion.”
The study received no outside funding. The authors report no relevant disclosures.
A version of this article first appeared on Medscape.com.
FROM ISC 2022