Stroke

Young stroke patients have an increased risk of being diagnosed with a new cancer in the years following their stroke, a new study shows, raising the possibility that the stroke might be the first manifestation of an underlying cancer.

The data were presented by Jamie Verhoeven, MD, Radboud University Medical Centre, the Netherlands, at the recent European Stroke Organisation Conference 2022.

Dr. Verhoeven noted that 10% of all stroke cases occur in individuals younger than 50 years. During the past few decades, the incidence of stroke in the young has steadily increased, whereas the incidence of stroke in older adults has stabilized or decreased.

“Stroke in the young differs from stroke in older patients, and one of the major differences is that stroke in the young has a higher proportion of cryptogenic stroke, with no clear cause found in over one-third of patients,” she said.

Also, having an active cancer is known to be a risk factor for thrombosis. This association is strongest in venous thrombosis and has been less well investigated in arterial thrombosis, Dr. Verhoeven reported.

Her group aimed to investigate whether in some patients with cryptogenic stroke, this may be the first manifestation of an underlying cancer. “If this hypothesis is true, then it would be more obvious in young patients who have a higher incidence of cryptogenic stroke,” she said.

They performed a population-based observational cohort study using diagnostic ICD codes from the national Hospital Discharge Registry in the Netherlands and the Dutch Population Registry from 1998 to 2019.

Patients with a history of cancer before their first stroke and those with central nervous system cancers at the time of stroke or nonmelanoma skin cancers (which have been shown to have no systemic effects) were excluded.

Reference data came from the Netherlands Comprehensive Cancer Organisation, which collects data on all cancer diagnoses in the country.

The researchers identified 27,616 young stroke patients (age range, 15-49 years; median age, 45 years) and 362,782 older stroke patients (age range, 50 years and older; median age, 76 years).

The cumulative incidence of any cancer at 10 years was 3.7% in the younger group and 8.5% in the older group.

The data were compared with matched peers from the general population. The main outcome measures were cumulative incidence of first-ever cancer after stroke (stratified by stroke subtype, age and sex) and standardized incidence rates.

Results showed that the risk for cancer was higher in the younger age group than in the matched general population.

In this age group, the 1-year risk of any new cancer was 2.6 times higher (95% confidence interval, 2.2-3.1) after ischemic stroke and 5.4 times (95% CI, 3.8-7.3) after intracerebral hemorrhage than in matched peers from the general population.

In contrast, in stroke patients older than 50 years, the 1-year risk for any new cancer was 1.2 times higher than the general population after either ischemic or hemorrhagic stroke.

“The younger patients have a higher risk increase of cancer than older patients, and this risk increase is most evident in the first 1 to 2 years after stroke but remains statistically significant for up to 5 to 8 years later,” Dr. Verhoeven said.

The cancers that were most involved in this risk increase were those of the lower respiratory tract, hematologic cancers, and gastrointestinal cancers.

The main strength of this study was the use of national databases that allowed for a very large sample size, but this brings with it the danger of misclassification of events and the lack of clinical data, Dr. Verhoeven noted.

“Young stroke patients are at increased risk of developing a new cancer in the years following their stroke compared to peers from the general population, but this risk is only marginally increased in the older stroke population,” she concluded.

She pointed out that it is not possible to confirm any causal relation from this study design, but a clear association has been shown.

“We need more studies into this field. We need a large clinical dataset to examine which clinical phenotypes are associated with possible underlying cancers to identify which patients are most at risk. We are already working on this,” she said. “Then it remains to be investigated whether screening for an underlying cancer should be added to the diagnostic workup in young stroke patients.”

Commenting on the study after the presentation, William Whiteley, BM, PhD, a clinical epidemiologist at the University of Edinburgh, Scotland, and a consultant neurologist in NHS Lothian, said it was difficult to know whether the link shown between stroke and cancer was causal, but the effect size in this study was “quite large.”

He pointed out that the associations with bowel and lung cancer could be due to shared risk factors, such as smoking, but he said the finding on a link with hematologic cancers is “interesting.”

Noting that there are links between hematologic cancers and thrombotic events, he said: “People have wondered if that is because of clonal expansion, which has been shown to increase the risk of atherosclerosis, so the question is whether this is some kind of common risk factor here.”

Dr. Verhoeven said she did not believe that shared risk factors fully explained the difference in increased risks between young and older patients.

“It does not fully explain why the risk of cancer is specifically higher in the first 1 to 2 years after the stroke diagnosis. I would think if it was just shared risk factors, the risk increase should remain relatively stable, or even increase due to the build-up of exposure to risk factors over the years,” she said.

Dr. Whiteley said that data like these are “really useful in trying to estimate these associations and it gives us some hypotheses to investigate in smaller mechanistic studies.”

Asked whether these data justify screening younger cryptogenic stroke patients more systematically for cancer, Dr. Whiteley replied: “I think we need some absolute risk estimates for that; for example, what proportion of younger patients would be at risk over the next few years when that screening would make a difference.”

Dr. Verhoeven reports no disclosures.

A version of this article first appeared on Medscape.com.

Young stroke patients have an increased risk of being diagnosed with a new cancer in the years following their stroke, a new study shows, raising the possibility that the stroke might be the first manifestation of an underlying cancer.

The data were presented by Jamie Verhoeven, MD, Radboud University Medical Centre, the Netherlands, at the recent European Stroke Organisation Conference 2022.

Dr. Verhoeven noted that 10% of all stroke cases occur in individuals younger than 50 years. During the past few decades, the incidence of stroke in the young has steadily increased, whereas the incidence of stroke in older adults has stabilized or decreased.

“Stroke in the young differs from stroke in older patients, and one of the major differences is that stroke in the young has a higher proportion of cryptogenic stroke, with no clear cause found in over one-third of patients,” she said.

Also, having an active cancer is known to be a risk factor for thrombosis. This association is strongest in venous thrombosis and has been less well investigated in arterial thrombosis, Dr. Verhoeven reported.

Her group aimed to investigate whether in some patients with cryptogenic stroke, this may be the first manifestation of an underlying cancer. “If this hypothesis is true, then it would be more obvious in young patients who have a higher incidence of cryptogenic stroke,” she said.

They performed a population-based observational cohort study using diagnostic ICD codes from the national Hospital Discharge Registry in the Netherlands and the Dutch Population Registry from 1998 to 2019.

Patients with a history of cancer before their first stroke and those with central nervous system cancers at the time of stroke or nonmelanoma skin cancers (which have been shown to have no systemic effects) were excluded.

Reference data came from the Netherlands Comprehensive Cancer Organisation, which collects data on all cancer diagnoses in the country.

The researchers identified 27,616 young stroke patients (age range, 15-49 years; median age, 45 years) and 362,782 older stroke patients (age range, 50 years and older; median age, 76 years).

The cumulative incidence of any cancer at 10 years was 3.7% in the younger group and 8.5% in the older group.

The data were compared with matched peers from the general population. The main outcome measures were cumulative incidence of first-ever cancer after stroke (stratified by stroke subtype, age and sex) and standardized incidence rates.

Results showed that the risk for cancer was higher in the younger age group than in the matched general population.

In this age group, the 1-year risk of any new cancer was 2.6 times higher (95% confidence interval, 2.2-3.1) after ischemic stroke and 5.4 times (95% CI, 3.8-7.3) after intracerebral hemorrhage than in matched peers from the general population.

In contrast, in stroke patients older than 50 years, the 1-year risk for any new cancer was 1.2 times higher than the general population after either ischemic or hemorrhagic stroke.

“The younger patients have a higher risk increase of cancer than older patients, and this risk increase is most evident in the first 1 to 2 years after stroke but remains statistically significant for up to 5 to 8 years later,” Dr. Verhoeven said.

The cancers that were most involved in this risk increase were those of the lower respiratory tract, hematologic cancers, and gastrointestinal cancers.

The main strength of this study was the use of national databases that allowed for a very large sample size, but this brings with it the danger of misclassification of events and the lack of clinical data, Dr. Verhoeven noted.

“Young stroke patients are at increased risk of developing a new cancer in the years following their stroke compared to peers from the general population, but this risk is only marginally increased in the older stroke population,” she concluded.

She pointed out that it is not possible to confirm any causal relation from this study design, but a clear association has been shown.

“We need more studies into this field. We need a large clinical dataset to examine which clinical phenotypes are associated with possible underlying cancers to identify which patients are most at risk. We are already working on this,” she said. “Then it remains to be investigated whether screening for an underlying cancer should be added to the diagnostic workup in young stroke patients.”

Commenting on the study after the presentation, William Whiteley, BM, PhD, a clinical epidemiologist at the University of Edinburgh, Scotland, and a consultant neurologist in NHS Lothian, said it was difficult to know whether the link shown between stroke and cancer was causal, but the effect size in this study was “quite large.”

He pointed out that the associations with bowel and lung cancer could be due to shared risk factors, such as smoking, but he said the finding on a link with hematologic cancers is “interesting.”

Noting that there are links between hematologic cancers and thrombotic events, he said: “People have wondered if that is because of clonal expansion, which has been shown to increase the risk of atherosclerosis, so the question is whether this is some kind of common risk factor here.”

Dr. Verhoeven said she did not believe that shared risk factors fully explained the difference in increased risks between young and older patients.

“It does not fully explain why the risk of cancer is specifically higher in the first 1 to 2 years after the stroke diagnosis. I would think if it was just shared risk factors, the risk increase should remain relatively stable, or even increase due to the build-up of exposure to risk factors over the years,” she said.

Dr. Whiteley said that data like these are “really useful in trying to estimate these associations and it gives us some hypotheses to investigate in smaller mechanistic studies.”

Asked whether these data justify screening younger cryptogenic stroke patients more systematically for cancer, Dr. Whiteley replied: “I think we need some absolute risk estimates for that; for example, what proportion of younger patients would be at risk over the next few years when that screening would make a difference.”

Dr. Verhoeven reports no disclosures.

A version of this article first appeared on Medscape.com.

Young stroke patients have an increased risk of being diagnosed with a new cancer in the years following their stroke, a new study shows, raising the possibility that the stroke might be the first manifestation of an underlying cancer.

The data were presented by Jamie Verhoeven, MD, Radboud University Medical Centre, the Netherlands, at the recent European Stroke Organisation Conference 2022.

Dr. Verhoeven noted that 10% of all stroke cases occur in individuals younger than 50 years. During the past few decades, the incidence of stroke in the young has steadily increased, whereas the incidence of stroke in older adults has stabilized or decreased.

“Stroke in the young differs from stroke in older patients, and one of the major differences is that stroke in the young has a higher proportion of cryptogenic stroke, with no clear cause found in over one-third of patients,” she said.

Also, having an active cancer is known to be a risk factor for thrombosis. This association is strongest in venous thrombosis and has been less well investigated in arterial thrombosis, Dr. Verhoeven reported.

Her group aimed to investigate whether in some patients with cryptogenic stroke, this may be the first manifestation of an underlying cancer. “If this hypothesis is true, then it would be more obvious in young patients who have a higher incidence of cryptogenic stroke,” she said.

They performed a population-based observational cohort study using diagnostic ICD codes from the national Hospital Discharge Registry in the Netherlands and the Dutch Population Registry from 1998 to 2019.

Patients with a history of cancer before their first stroke and those with central nervous system cancers at the time of stroke or nonmelanoma skin cancers (which have been shown to have no systemic effects) were excluded.

Reference data came from the Netherlands Comprehensive Cancer Organisation, which collects data on all cancer diagnoses in the country.

The researchers identified 27,616 young stroke patients (age range, 15-49 years; median age, 45 years) and 362,782 older stroke patients (age range, 50 years and older; median age, 76 years).

The cumulative incidence of any cancer at 10 years was 3.7% in the younger group and 8.5% in the older group.

The data were compared with matched peers from the general population. The main outcome measures were cumulative incidence of first-ever cancer after stroke (stratified by stroke subtype, age and sex) and standardized incidence rates.

Results showed that the risk for cancer was higher in the younger age group than in the matched general population.

In this age group, the 1-year risk of any new cancer was 2.6 times higher (95% confidence interval, 2.2-3.1) after ischemic stroke and 5.4 times (95% CI, 3.8-7.3) after intracerebral hemorrhage than in matched peers from the general population.

In contrast, in stroke patients older than 50 years, the 1-year risk for any new cancer was 1.2 times higher than the general population after either ischemic or hemorrhagic stroke.

“The younger patients have a higher risk increase of cancer than older patients, and this risk increase is most evident in the first 1 to 2 years after stroke but remains statistically significant for up to 5 to 8 years later,” Dr. Verhoeven said.

The cancers that were most involved in this risk increase were those of the lower respiratory tract, hematologic cancers, and gastrointestinal cancers.

The main strength of this study was the use of national databases that allowed for a very large sample size, but this brings with it the danger of misclassification of events and the lack of clinical data, Dr. Verhoeven noted.

“Young stroke patients are at increased risk of developing a new cancer in the years following their stroke compared to peers from the general population, but this risk is only marginally increased in the older stroke population,” she concluded.

She pointed out that it is not possible to confirm any causal relation from this study design, but a clear association has been shown.

“We need more studies into this field. We need a large clinical dataset to examine which clinical phenotypes are associated with possible underlying cancers to identify which patients are most at risk. We are already working on this,” she said. “Then it remains to be investigated whether screening for an underlying cancer should be added to the diagnostic workup in young stroke patients.”

Commenting on the study after the presentation, William Whiteley, BM, PhD, a clinical epidemiologist at the University of Edinburgh, Scotland, and a consultant neurologist in NHS Lothian, said it was difficult to know whether the link shown between stroke and cancer was causal, but the effect size in this study was “quite large.”

He pointed out that the associations with bowel and lung cancer could be due to shared risk factors, such as smoking, but he said the finding on a link with hematologic cancers is “interesting.”

Noting that there are links between hematologic cancers and thrombotic events, he said: “People have wondered if that is because of clonal expansion, which has been shown to increase the risk of atherosclerosis, so the question is whether this is some kind of common risk factor here.”

Dr. Verhoeven said she did not believe that shared risk factors fully explained the difference in increased risks between young and older patients.

“It does not fully explain why the risk of cancer is specifically higher in the first 1 to 2 years after the stroke diagnosis. I would think if it was just shared risk factors, the risk increase should remain relatively stable, or even increase due to the build-up of exposure to risk factors over the years,” she said.

Dr. Whiteley said that data like these are “really useful in trying to estimate these associations and it gives us some hypotheses to investigate in smaller mechanistic studies.”

Asked whether these data justify screening younger cryptogenic stroke patients more systematically for cancer, Dr. Whiteley replied: “I think we need some absolute risk estimates for that; for example, what proportion of younger patients would be at risk over the next few years when that screening would make a difference.”

Dr. Verhoeven reports no disclosures.

A version of this article first appeared on Medscape.com.

Treatment with the diabetes drug exenatide was associated with a significant decrease in hyperglycemia in acute stroke patients, a new study shows.

The research could offer clinicians an alternative to insulin therapy to treat hyperglycemia and reduce glucose levels, which are elevated in up to 60% of stroke patients and associated with worse outcomes after stroke.

“Use of these diabetes drugs to control glucose in acute stroke has enormous potential,” said lead researcher Christopher Bladin, PhD, professor of neurology at Monash University and Eastern Health Clinical School, Australia.

The findings were presented at the European Stroke Organisation Conference (ESOC) 2022 annual meeting in Lyon, France.
 

A better fix than insulin?

Hyperglycemia is common in stroke patients, including those who have no prior history of diabetes. Among stroke patients with normal blood glucose upon admission, about 30% will develop hyperglycemia within 48 hours of stroke onset.

Previous research suggests that hyperglycemia is a poor prognostic factor in patients with stroke and may reduce the efficacy of reperfusion therapies such as thrombolysis and mechanical thrombectomy.

“We’ve been looking for different ways of treating hyperglycemia for quite some time, and one of the obvious ways is to use insulin therapy,” Dr. Bladin said. “But as we’ve seen from multiple studies, insulin therapy is difficult.”

Insulin treatment is resource-heavy, significantly increases the risk for hypoglycemia, and some studies suggest the therapy isn’t associated with better outcomes.

An advantage to a GLP-1 agonist-like exenatide, Dr. Bladin added, is that it’s glucose-dependent. As the glucose level falls, the drug’s efficacy diminishes. It is delivered via an autoinjector and easy to administer.

A case for more study

To study exenatide’s efficacy in reducing hyperglycemia and improving neurologic outcomes, researchers developed the phase 2, international, multicenter, randomized controlled TEXAIS trial.

The study enrolled 350 patients following an ischemic stroke. Within 9 hours of stroke onset, patients received either standard care or a subcutaneous injection of 5 mg of exenatide twice daily for 5 days.

On admission, 42% of patients had hyperglycemia, defined as blood glucose > 7.0 mmol/L.

The study’s primary outcome was at least an 8-point improvement in National Institutes of Health Stroke Scale (NIHSS) score by 7 days after treatment with exenatide. Although there was a trend toward better scores with exenatide, the score was not significantly different between groups (56.7% with standard care versus 61.2% with exenatide; adjusted odds ratio, 1.22; P = .38).

However, when the researchers examined hyperglycemia frequency, they found significantly lower incidence in patients treated with exenatide (P = .002).

There were no cases of hypoglycemia in either group, and only 4% of the study group reported nausea or vomiting.

“Clearly exenatide is having some benefit in terms of keeping glucose under control, reducing hyperglycemia,” Dr. Bladin said. “It certainly lends itself to a larger phase 3 study which can look at this more completely.”
 

Value to clinicians

Commenting on the findings, Yvonne Chun, PhD, honorary senior clinical lecturer at University of Edinburgh, noted that, even though the study didn’t find a significant association with improved neurological outcomes, the reduced risk for hypoglycemia makes exenatide an attractive alternative to insulin therapy in stroke patients.

“The results are of value to clinicians, as exenatide could potentially be a safer medication to administer than an insulin infusion in acute stroke patients with hyperglycemia,” Dr. Chun said. “There is less risk of hypoglycemia with exenatide compared to standard care.”

However, Dr. Chun noted that more study is needed before exenatide can replace standard care. Dr. Bladin agrees and would like to pursue a phase 3 trial with a modified design to answer questions raised by Dr. Chun and others.

“The next phase could consider changing the primary outcome to an ordinal shift analysis on modified Rankin Scale – a very commonly used primary outcome in stroke clinical trials to assess improvement in disability,” Dr. Chun said. “The primary outcome used in the presented trial – an 8-point improvement on NIHSS – seemed too ambitious and does not inform disability of the patient post stroke.”

Dr. Bladin said he would also like to see the next phase enroll more patients, examine a higher dose of exenatide, and include better stratification of patients with a history of diabetes. Such a trial could yield findings demonstrating the drug’s effectiveness at reducing hyperglycemia and improving outcomes after stroke, he said.

“I can see the day patients will come in with acute stroke, and as they’re coming into the emergency department, they’ll simply get their shot of exenatide because we know it’s safe to use, and it doesn’t cause hypoglycemia,” Dr. Bladin said. “And from the moment that patient arrives the glucose control is underway.”

Dr. Bladin and Dr. Chun reported no relevant financial relationships. Study funding was not disclosed.

A version of this article first appeared on Medscape.com.

Treatment with the diabetes drug exenatide was associated with a significant decrease in hyperglycemia in acute stroke patients, a new study shows.

The research could offer clinicians an alternative to insulin therapy to treat hyperglycemia and reduce glucose levels, which are elevated in up to 60% of stroke patients and associated with worse outcomes after stroke.

“Use of these diabetes drugs to control glucose in acute stroke has enormous potential,” said lead researcher Christopher Bladin, PhD, professor of neurology at Monash University and Eastern Health Clinical School, Australia.

The findings were presented at the European Stroke Organisation Conference (ESOC) 2022 annual meeting in Lyon, France.
 

A better fix than insulin?

Hyperglycemia is common in stroke patients, including those who have no prior history of diabetes. Among stroke patients with normal blood glucose upon admission, about 30% will develop hyperglycemia within 48 hours of stroke onset.

Previous research suggests that hyperglycemia is a poor prognostic factor in patients with stroke and may reduce the efficacy of reperfusion therapies such as thrombolysis and mechanical thrombectomy.

“We’ve been looking for different ways of treating hyperglycemia for quite some time, and one of the obvious ways is to use insulin therapy,” Dr. Bladin said. “But as we’ve seen from multiple studies, insulin therapy is difficult.”

Insulin treatment is resource-heavy, significantly increases the risk for hypoglycemia, and some studies suggest the therapy isn’t associated with better outcomes.

An advantage to a GLP-1 agonist-like exenatide, Dr. Bladin added, is that it’s glucose-dependent. As the glucose level falls, the drug’s efficacy diminishes. It is delivered via an autoinjector and easy to administer.

A case for more study

To study exenatide’s efficacy in reducing hyperglycemia and improving neurologic outcomes, researchers developed the phase 2, international, multicenter, randomized controlled TEXAIS trial.

The study enrolled 350 patients following an ischemic stroke. Within 9 hours of stroke onset, patients received either standard care or a subcutaneous injection of 5 mg of exenatide twice daily for 5 days.

On admission, 42% of patients had hyperglycemia, defined as blood glucose > 7.0 mmol/L.

The study’s primary outcome was at least an 8-point improvement in National Institutes of Health Stroke Scale (NIHSS) score by 7 days after treatment with exenatide. Although there was a trend toward better scores with exenatide, the score was not significantly different between groups (56.7% with standard care versus 61.2% with exenatide; adjusted odds ratio, 1.22; P = .38).

However, when the researchers examined hyperglycemia frequency, they found significantly lower incidence in patients treated with exenatide (P = .002).

There were no cases of hypoglycemia in either group, and only 4% of the study group reported nausea or vomiting.

“Clearly exenatide is having some benefit in terms of keeping glucose under control, reducing hyperglycemia,” Dr. Bladin said. “It certainly lends itself to a larger phase 3 study which can look at this more completely.”
 

Value to clinicians

Commenting on the findings, Yvonne Chun, PhD, honorary senior clinical lecturer at University of Edinburgh, noted that, even though the study didn’t find a significant association with improved neurological outcomes, the reduced risk for hypoglycemia makes exenatide an attractive alternative to insulin therapy in stroke patients.

“The results are of value to clinicians, as exenatide could potentially be a safer medication to administer than an insulin infusion in acute stroke patients with hyperglycemia,” Dr. Chun said. “There is less risk of hypoglycemia with exenatide compared to standard care.”

However, Dr. Chun noted that more study is needed before exenatide can replace standard care. Dr. Bladin agrees and would like to pursue a phase 3 trial with a modified design to answer questions raised by Dr. Chun and others.

“The next phase could consider changing the primary outcome to an ordinal shift analysis on modified Rankin Scale – a very commonly used primary outcome in stroke clinical trials to assess improvement in disability,” Dr. Chun said. “The primary outcome used in the presented trial – an 8-point improvement on NIHSS – seemed too ambitious and does not inform disability of the patient post stroke.”

Dr. Bladin said he would also like to see the next phase enroll more patients, examine a higher dose of exenatide, and include better stratification of patients with a history of diabetes. Such a trial could yield findings demonstrating the drug’s effectiveness at reducing hyperglycemia and improving outcomes after stroke, he said.

“I can see the day patients will come in with acute stroke, and as they’re coming into the emergency department, they’ll simply get their shot of exenatide because we know it’s safe to use, and it doesn’t cause hypoglycemia,” Dr. Bladin said. “And from the moment that patient arrives the glucose control is underway.”

Dr. Bladin and Dr. Chun reported no relevant financial relationships. Study funding was not disclosed.

A version of this article first appeared on Medscape.com.

Treatment with the diabetes drug exenatide was associated with a significant decrease in hyperglycemia in acute stroke patients, a new study shows.

The research could offer clinicians an alternative to insulin therapy to treat hyperglycemia and reduce glucose levels, which are elevated in up to 60% of stroke patients and associated with worse outcomes after stroke.

“Use of these diabetes drugs to control glucose in acute stroke has enormous potential,” said lead researcher Christopher Bladin, PhD, professor of neurology at Monash University and Eastern Health Clinical School, Australia.

The findings were presented at the European Stroke Organisation Conference (ESOC) 2022 annual meeting in Lyon, France.
 

A better fix than insulin?

Hyperglycemia is common in stroke patients, including those who have no prior history of diabetes. Among stroke patients with normal blood glucose upon admission, about 30% will develop hyperglycemia within 48 hours of stroke onset.

Previous research suggests that hyperglycemia is a poor prognostic factor in patients with stroke and may reduce the efficacy of reperfusion therapies such as thrombolysis and mechanical thrombectomy.

“We’ve been looking for different ways of treating hyperglycemia for quite some time, and one of the obvious ways is to use insulin therapy,” Dr. Bladin said. “But as we’ve seen from multiple studies, insulin therapy is difficult.”

Insulin treatment is resource-heavy, significantly increases the risk for hypoglycemia, and some studies suggest the therapy isn’t associated with better outcomes.

An advantage to a GLP-1 agonist-like exenatide, Dr. Bladin added, is that it’s glucose-dependent. As the glucose level falls, the drug’s efficacy diminishes. It is delivered via an autoinjector and easy to administer.

A case for more study

To study exenatide’s efficacy in reducing hyperglycemia and improving neurologic outcomes, researchers developed the phase 2, international, multicenter, randomized controlled TEXAIS trial.

The study enrolled 350 patients following an ischemic stroke. Within 9 hours of stroke onset, patients received either standard care or a subcutaneous injection of 5 mg of exenatide twice daily for 5 days.

On admission, 42% of patients had hyperglycemia, defined as blood glucose > 7.0 mmol/L.

The study’s primary outcome was at least an 8-point improvement in National Institutes of Health Stroke Scale (NIHSS) score by 7 days after treatment with exenatide. Although there was a trend toward better scores with exenatide, the score was not significantly different between groups (56.7% with standard care versus 61.2% with exenatide; adjusted odds ratio, 1.22; P = .38).

However, when the researchers examined hyperglycemia frequency, they found significantly lower incidence in patients treated with exenatide (P = .002).

There were no cases of hypoglycemia in either group, and only 4% of the study group reported nausea or vomiting.

“Clearly exenatide is having some benefit in terms of keeping glucose under control, reducing hyperglycemia,” Dr. Bladin said. “It certainly lends itself to a larger phase 3 study which can look at this more completely.”
 

Value to clinicians

Commenting on the findings, Yvonne Chun, PhD, honorary senior clinical lecturer at University of Edinburgh, noted that, even though the study didn’t find a significant association with improved neurological outcomes, the reduced risk for hypoglycemia makes exenatide an attractive alternative to insulin therapy in stroke patients.

“The results are of value to clinicians, as exenatide could potentially be a safer medication to administer than an insulin infusion in acute stroke patients with hyperglycemia,” Dr. Chun said. “There is less risk of hypoglycemia with exenatide compared to standard care.”

However, Dr. Chun noted that more study is needed before exenatide can replace standard care. Dr. Bladin agrees and would like to pursue a phase 3 trial with a modified design to answer questions raised by Dr. Chun and others.

“The next phase could consider changing the primary outcome to an ordinal shift analysis on modified Rankin Scale – a very commonly used primary outcome in stroke clinical trials to assess improvement in disability,” Dr. Chun said. “The primary outcome used in the presented trial – an 8-point improvement on NIHSS – seemed too ambitious and does not inform disability of the patient post stroke.”

Dr. Bladin said he would also like to see the next phase enroll more patients, examine a higher dose of exenatide, and include better stratification of patients with a history of diabetes. Such a trial could yield findings demonstrating the drug’s effectiveness at reducing hyperglycemia and improving outcomes after stroke, he said.

“I can see the day patients will come in with acute stroke, and as they’re coming into the emergency department, they’ll simply get their shot of exenatide because we know it’s safe to use, and it doesn’t cause hypoglycemia,” Dr. Bladin said. “And from the moment that patient arrives the glucose control is underway.”

Dr. Bladin and Dr. Chun reported no relevant financial relationships. Study funding was not disclosed.

A version of this article first appeared on Medscape.com.

Espresso consumption is associated with higher total cholesterol levels, a population-based, cross-sectional study suggests.

Elevations in serum total cholesterol level were significantly linked to espresso consumption, particularly in men, Åsne Lirhus Svatun, of the Arctic University of Norway, Tromsø, and colleagues reported.

Drinking boiled/plunger coffee was associated with significantly higher serum total cholesterol levels in women and men. There was a significant relationship between filtered coffee consumption and total cholesterol, but only among women, the researchers reported.

SorJongAng/Thinkstock.com

“Doctors could become mindful of asking about coffee consumption when taking up the history of patients with elevated serum cholesterol,” study author Maja-Lisa Løchen, MD, PhD, of the Arctic University of Norway, said in an interview.

“Guiding patients to change from plunger coffee or other unfiltered coffee types to filtered or instant coffee could be a part of a lifestyle intervention to lower serum cholesterol levels.”

The results were published online in the journal Open Heart.

Previous studies of the relationship between serum cholesterol and espresso have had varying outcomes, the researchers noted.

Given that coffee consumption is high worldwide, even slight health effects can have substantial health consequences, the researchers noted. “Coffee was included for the first time in the 2021 ESC [European Society of Cardiology] guidelines on cardiovascular disease prevention in clinical practice. Increased knowledge on espresso coffee’s association with serum cholesterol will improve the recommendations regarding coffee consumption.”

“I don’t think that the findings in this paper are necessarily enough to change any advice about coffee,” said David Kao, MD, an associate professor medicine at the University of Colorado at Denver, Aurora, in commenting on the findings. “This is partly because the most important thing at the end of the day is whether subsequent events like heart attack or stroke increased or decreased. This analysis was not designed to answer that question.”

“If one has to choose between this study, which would suggest to drink less coffee to maintain low cholesterol, and the others, which would suggest increasing coffee consumption might reduce risk of multiple kinds of CVD, one should choose the latter,” Dr. Kao concluded.

In the current study, the investigators assessed 21,083 participants in the Tromsø Study in Northern Norway. The mean age of the participants was 56.4 years. Using multivariable linear regression, the researchers compared the relationship between each level of coffee consumption with no coffee consumption as the reference point and serum total cholesterol as the dependent variable. They tested for sex differences and adjusted for relevant covariates.

The findings indicate that drinking three to five cups of espresso each day was significantly linked with greater serum total cholesterol by 0.16 mmol/L (95% confidence interval, 0.07-0.24) for men and by 0.09 mmol/L (95% CI, 0.01-0.17) for women in comparison with participants who did not drink espresso daily.

Compared with individuals who did not drink plunger/boiled coffee, consumption of six or more cups of plunger/boiled coffee each day was linked with elevated serum total cholesterol levels by 0.23 mmol/L (95% CI, 0.08-0.38) for men and 0.30 mmol/L (95% CI, 0.13-0.48) for women.

Notably, for women but not men, there was an increase in serum total cholesterol of 0.11 mmol/L (95% CI, 0.03-0.19) in association with drinking six or more cups of filtered coffee per day.

When excluding participants who did not drink instant coffee, drinking instant coffee yielded a significant linear pattern for both men and women, but there was not a dose-dependent association.

These data show that sex differences were significant for every coffee type except plunger/boiled coffee, the authors noted.

Limitations of the study include its cross-sectional design; lack of generalizability of the data, given that the cohort primarily consisted of elderly adults and middle-aged White persons; and the fact that the study did not adjust for all confounding variables, the researchers noted.

Also among the study’s limitations were that some data were self-reported, and the missing indicator approach was implemented to assess data, the authors added.

Future research efforts should focus on following this cohort over many years to determine how consumption of various types of coffee is linked with events such as heart failure, stroke, and myocardial infarction. This insight would be important in offering guidance on whether the style of coffee preparation matters, concluded Dr. Kao.

The study was supported by a number of sources, including the Arctic University of Norway and the Northern Norway Regional Health Authority. The study investigators reported no conflicts of interest.

A version of this article first appeared on Medscape.com.

Espresso consumption is associated with higher total cholesterol levels, a population-based, cross-sectional study suggests.

Elevations in serum total cholesterol level were significantly linked to espresso consumption, particularly in men, Åsne Lirhus Svatun, of the Arctic University of Norway, Tromsø, and colleagues reported.

Drinking boiled/plunger coffee was associated with significantly higher serum total cholesterol levels in women and men. There was a significant relationship between filtered coffee consumption and total cholesterol, but only among women, the researchers reported.

SorJongAng/Thinkstock.com

“Doctors could become mindful of asking about coffee consumption when taking up the history of patients with elevated serum cholesterol,” study author Maja-Lisa Løchen, MD, PhD, of the Arctic University of Norway, said in an interview.

“Guiding patients to change from plunger coffee or other unfiltered coffee types to filtered or instant coffee could be a part of a lifestyle intervention to lower serum cholesterol levels.”

The results were published online in the journal Open Heart.

Previous studies of the relationship between serum cholesterol and espresso have had varying outcomes, the researchers noted.

Given that coffee consumption is high worldwide, even slight health effects can have substantial health consequences, the researchers noted. “Coffee was included for the first time in the 2021 ESC [European Society of Cardiology] guidelines on cardiovascular disease prevention in clinical practice. Increased knowledge on espresso coffee’s association with serum cholesterol will improve the recommendations regarding coffee consumption.”

“I don’t think that the findings in this paper are necessarily enough to change any advice about coffee,” said David Kao, MD, an associate professor medicine at the University of Colorado at Denver, Aurora, in commenting on the findings. “This is partly because the most important thing at the end of the day is whether subsequent events like heart attack or stroke increased or decreased. This analysis was not designed to answer that question.”

“If one has to choose between this study, which would suggest to drink less coffee to maintain low cholesterol, and the others, which would suggest increasing coffee consumption might reduce risk of multiple kinds of CVD, one should choose the latter,” Dr. Kao concluded.

In the current study, the investigators assessed 21,083 participants in the Tromsø Study in Northern Norway. The mean age of the participants was 56.4 years. Using multivariable linear regression, the researchers compared the relationship between each level of coffee consumption with no coffee consumption as the reference point and serum total cholesterol as the dependent variable. They tested for sex differences and adjusted for relevant covariates.

The findings indicate that drinking three to five cups of espresso each day was significantly linked with greater serum total cholesterol by 0.16 mmol/L (95% confidence interval, 0.07-0.24) for men and by 0.09 mmol/L (95% CI, 0.01-0.17) for women in comparison with participants who did not drink espresso daily.

Compared with individuals who did not drink plunger/boiled coffee, consumption of six or more cups of plunger/boiled coffee each day was linked with elevated serum total cholesterol levels by 0.23 mmol/L (95% CI, 0.08-0.38) for men and 0.30 mmol/L (95% CI, 0.13-0.48) for women.

Notably, for women but not men, there was an increase in serum total cholesterol of 0.11 mmol/L (95% CI, 0.03-0.19) in association with drinking six or more cups of filtered coffee per day.

When excluding participants who did not drink instant coffee, drinking instant coffee yielded a significant linear pattern for both men and women, but there was not a dose-dependent association.

These data show that sex differences were significant for every coffee type except plunger/boiled coffee, the authors noted.

Limitations of the study include its cross-sectional design; lack of generalizability of the data, given that the cohort primarily consisted of elderly adults and middle-aged White persons; and the fact that the study did not adjust for all confounding variables, the researchers noted.

Also among the study’s limitations were that some data were self-reported, and the missing indicator approach was implemented to assess data, the authors added.

Future research efforts should focus on following this cohort over many years to determine how consumption of various types of coffee is linked with events such as heart failure, stroke, and myocardial infarction. This insight would be important in offering guidance on whether the style of coffee preparation matters, concluded Dr. Kao.

The study was supported by a number of sources, including the Arctic University of Norway and the Northern Norway Regional Health Authority. The study investigators reported no conflicts of interest.

A version of this article first appeared on Medscape.com.

Espresso consumption is associated with higher total cholesterol levels, a population-based, cross-sectional study suggests.

Elevations in serum total cholesterol level were significantly linked to espresso consumption, particularly in men, Åsne Lirhus Svatun, of the Arctic University of Norway, Tromsø, and colleagues reported.

Drinking boiled/plunger coffee was associated with significantly higher serum total cholesterol levels in women and men. There was a significant relationship between filtered coffee consumption and total cholesterol, but only among women, the researchers reported.

SorJongAng/Thinkstock.com

“Doctors could become mindful of asking about coffee consumption when taking up the history of patients with elevated serum cholesterol,” study author Maja-Lisa Løchen, MD, PhD, of the Arctic University of Norway, said in an interview.

“Guiding patients to change from plunger coffee or other unfiltered coffee types to filtered or instant coffee could be a part of a lifestyle intervention to lower serum cholesterol levels.”

The results were published online in the journal Open Heart.

Previous studies of the relationship between serum cholesterol and espresso have had varying outcomes, the researchers noted.

Given that coffee consumption is high worldwide, even slight health effects can have substantial health consequences, the researchers noted. “Coffee was included for the first time in the 2021 ESC [European Society of Cardiology] guidelines on cardiovascular disease prevention in clinical practice. Increased knowledge on espresso coffee’s association with serum cholesterol will improve the recommendations regarding coffee consumption.”

“I don’t think that the findings in this paper are necessarily enough to change any advice about coffee,” said David Kao, MD, an associate professor medicine at the University of Colorado at Denver, Aurora, in commenting on the findings. “This is partly because the most important thing at the end of the day is whether subsequent events like heart attack or stroke increased or decreased. This analysis was not designed to answer that question.”

“If one has to choose between this study, which would suggest to drink less coffee to maintain low cholesterol, and the others, which would suggest increasing coffee consumption might reduce risk of multiple kinds of CVD, one should choose the latter,” Dr. Kao concluded.

In the current study, the investigators assessed 21,083 participants in the Tromsø Study in Northern Norway. The mean age of the participants was 56.4 years. Using multivariable linear regression, the researchers compared the relationship between each level of coffee consumption with no coffee consumption as the reference point and serum total cholesterol as the dependent variable. They tested for sex differences and adjusted for relevant covariates.

The findings indicate that drinking three to five cups of espresso each day was significantly linked with greater serum total cholesterol by 0.16 mmol/L (95% confidence interval, 0.07-0.24) for men and by 0.09 mmol/L (95% CI, 0.01-0.17) for women in comparison with participants who did not drink espresso daily.

Compared with individuals who did not drink plunger/boiled coffee, consumption of six or more cups of plunger/boiled coffee each day was linked with elevated serum total cholesterol levels by 0.23 mmol/L (95% CI, 0.08-0.38) for men and 0.30 mmol/L (95% CI, 0.13-0.48) for women.

Notably, for women but not men, there was an increase in serum total cholesterol of 0.11 mmol/L (95% CI, 0.03-0.19) in association with drinking six or more cups of filtered coffee per day.

When excluding participants who did not drink instant coffee, drinking instant coffee yielded a significant linear pattern for both men and women, but there was not a dose-dependent association.

These data show that sex differences were significant for every coffee type except plunger/boiled coffee, the authors noted.

Limitations of the study include its cross-sectional design; lack of generalizability of the data, given that the cohort primarily consisted of elderly adults and middle-aged White persons; and the fact that the study did not adjust for all confounding variables, the researchers noted.

Also among the study’s limitations were that some data were self-reported, and the missing indicator approach was implemented to assess data, the authors added.

Future research efforts should focus on following this cohort over many years to determine how consumption of various types of coffee is linked with events such as heart failure, stroke, and myocardial infarction. This insight would be important in offering guidance on whether the style of coffee preparation matters, concluded Dr. Kao.

The study was supported by a number of sources, including the Arctic University of Norway and the Northern Norway Regional Health Authority. The study investigators reported no conflicts of interest.

A version of this article first appeared on Medscape.com.

A large percentage of studies in neurology and psychiatry over the past decade have failed to account for differences between the sexes, according to a team of Canadian researchers.

In a survey of more than 3,000 papers published in six neuroscience and psychiatry journals from 2009 to 2019, researchers found that only 5% analyzed sex as a variable.

“Despite the fact there are papers that are using males and females in the studies, they’re not using the males and females in the way that would optimally find the possibility of sex differences,” lead author Liisa A.M. Galea, PhD, told this news organization. Dr. Galea is a professor and distinguished scholar at the Djavad Mowafaghian Center for Brain Health at the University of British Columbia in Vancouver.

The study was published online in Nature Communications.
 

Optimal design uncommon

Differences in how neurologic and psychiatric diseases affect men and women have been well documented. Women, for example, are more susceptible to severe stroke, and men are more prone to cognitive decline with schizophrenia. With Alzheimer’s disease, women typically have more severe cognitive defects.

The researchers surveyed 3,193 papers that included a multitude of studies. Although most of the papers reported studies that included both sexes, only 19% of surveyed studies used what Dr. Galea called an optimal design for the discovery of sex differences. “What I mean by ‘optimally’ is the design of the experiments and the analysis of sex as a variable,” she said. And in 2019, only 5% of the studies used sex as a variable for determining differences between the sexes, the study found.

In the current research, two authors read the methods and results of each study described in each paper, Dr. Galea said. The readers noted whether the paper reported the study sample size and whether the studies used a balanced design. The surveyed journals include Nature Neuroscience, Neuron, Journal of Neuroscience, Molecular Psychiatry, Biological Psychiatry, and Neuropsychopharmacology.
 

‘Not much is changing’

“I had a suspicion that this was happening,” Dr. Galea said. “I didn’t know that it’s so bad, to be fair.” The “good news story,” she said, is that more papers considered sex as a factor in the later years surveyed. In 2019, more than 95% of papers across both disciplines reported participants’ sex, compared with about 70% in 2009. However, less than 20% of the papers in all study years reported studies that used sex optimally to determine differences between the sexes.

“The other thing that shocked me,” Dr. Galea said, “was that even despite the fact that we saw this increase in the number of papers that were using males and females, we didn’t see the sort of corresponding increase in those that were using ‘optimal design’ or ‘optimal analysis,’ ” Dr. Galea said. In 2009, 14% of papers used optimal design and 2% used optimal analysis for determining sex differences. By 2019, those percentages were 19% and 5%, respectively.

But even the papers that used both sexes had shortcomings, the study found. Just over one-third of these papers (34.5%) didn’t use a balanced design. Just over one-quarter (25.9%) didn’t identify the sample size, a shortcoming that marked 18% of these studies in 2009 and 33% in 2019. Fifteen percent of papers examined included studies that used both sexes inconsistently.

“That matters, because other studies have found that about 20% of papers are doing some kind of analysis with sex, but we had a suspicion that a lot of studies would include sex as a covariate,” Dr. Galea said. “Essentially what that does is, you remove that variable from the data. So, any statistical variation due to sex is then gone.

“The problem with that,” she added, “is you’re not actually looking to see if there’s an influence of sex; you’re removing it.”

Dr. Galea noted that this study points to a need for funding agencies to demand that researchers meet their mandates on sex- and gender-based analysis. “Despite the mandates, not much is really changing as far as the analysis or design of experiments, and we need to figure out how to change that,” she said. “We need to figure out how to get researchers more interested to use the power of studying sex differences.”
 

‘Not surprising, but disappointing’

Vladimir Hachinski, MD, professor of neurology and epidemiology at Western University in London, Ont., and former editor in chief of Stroke, told this news organization that women have almost twice the life risk of developing dementia, are at higher risk of stroke below age 35 years, and have more severe strokes and higher rates of disability at any age.

Commenting on the current study, Dr. Hachinski said, “It’s not surprising, but it’s disappointing, because we’ve known the difference for a long time.” He added, “The paper is very important because we were not aware that it was that bad.”

Dr. Hachinski also stated, “This paper needs a lot of reading. It’s a great resource, and it should be highlighted as one of those things that needs to be addressed, because it matters.”

The study was funded by a Natural Sciences and Engineering Research Council of Canada grant and by the British Columbia Women’s Foundation. Dr. Galea and Hachinski had no relevant disclosures.

A version of this article first appeared on Medscape.com.

A large percentage of studies in neurology and psychiatry over the past decade have failed to account for differences between the sexes, according to a team of Canadian researchers.

In a survey of more than 3,000 papers published in six neuroscience and psychiatry journals from 2009 to 2019, researchers found that only 5% analyzed sex as a variable.

“Despite the fact there are papers that are using males and females in the studies, they’re not using the males and females in the way that would optimally find the possibility of sex differences,” lead author Liisa A.M. Galea, PhD, told this news organization. Dr. Galea is a professor and distinguished scholar at the Djavad Mowafaghian Center for Brain Health at the University of British Columbia in Vancouver.

The study was published online in Nature Communications.
 

Optimal design uncommon

Differences in how neurologic and psychiatric diseases affect men and women have been well documented. Women, for example, are more susceptible to severe stroke, and men are more prone to cognitive decline with schizophrenia. With Alzheimer’s disease, women typically have more severe cognitive defects.

The researchers surveyed 3,193 papers that included a multitude of studies. Although most of the papers reported studies that included both sexes, only 19% of surveyed studies used what Dr. Galea called an optimal design for the discovery of sex differences. “What I mean by ‘optimally’ is the design of the experiments and the analysis of sex as a variable,” she said. And in 2019, only 5% of the studies used sex as a variable for determining differences between the sexes, the study found.

In the current research, two authors read the methods and results of each study described in each paper, Dr. Galea said. The readers noted whether the paper reported the study sample size and whether the studies used a balanced design. The surveyed journals include Nature Neuroscience, Neuron, Journal of Neuroscience, Molecular Psychiatry, Biological Psychiatry, and Neuropsychopharmacology.
 

‘Not much is changing’

“I had a suspicion that this was happening,” Dr. Galea said. “I didn’t know that it’s so bad, to be fair.” The “good news story,” she said, is that more papers considered sex as a factor in the later years surveyed. In 2019, more than 95% of papers across both disciplines reported participants’ sex, compared with about 70% in 2009. However, less than 20% of the papers in all study years reported studies that used sex optimally to determine differences between the sexes.

“The other thing that shocked me,” Dr. Galea said, “was that even despite the fact that we saw this increase in the number of papers that were using males and females, we didn’t see the sort of corresponding increase in those that were using ‘optimal design’ or ‘optimal analysis,’ ” Dr. Galea said. In 2009, 14% of papers used optimal design and 2% used optimal analysis for determining sex differences. By 2019, those percentages were 19% and 5%, respectively.

But even the papers that used both sexes had shortcomings, the study found. Just over one-third of these papers (34.5%) didn’t use a balanced design. Just over one-quarter (25.9%) didn’t identify the sample size, a shortcoming that marked 18% of these studies in 2009 and 33% in 2019. Fifteen percent of papers examined included studies that used both sexes inconsistently.

“That matters, because other studies have found that about 20% of papers are doing some kind of analysis with sex, but we had a suspicion that a lot of studies would include sex as a covariate,” Dr. Galea said. “Essentially what that does is, you remove that variable from the data. So, any statistical variation due to sex is then gone.

“The problem with that,” she added, “is you’re not actually looking to see if there’s an influence of sex; you’re removing it.”

Dr. Galea noted that this study points to a need for funding agencies to demand that researchers meet their mandates on sex- and gender-based analysis. “Despite the mandates, not much is really changing as far as the analysis or design of experiments, and we need to figure out how to change that,” she said. “We need to figure out how to get researchers more interested to use the power of studying sex differences.”
 

‘Not surprising, but disappointing’

Vladimir Hachinski, MD, professor of neurology and epidemiology at Western University in London, Ont., and former editor in chief of Stroke, told this news organization that women have almost twice the life risk of developing dementia, are at higher risk of stroke below age 35 years, and have more severe strokes and higher rates of disability at any age.

Commenting on the current study, Dr. Hachinski said, “It’s not surprising, but it’s disappointing, because we’ve known the difference for a long time.” He added, “The paper is very important because we were not aware that it was that bad.”

Dr. Hachinski also stated, “This paper needs a lot of reading. It’s a great resource, and it should be highlighted as one of those things that needs to be addressed, because it matters.”

The study was funded by a Natural Sciences and Engineering Research Council of Canada grant and by the British Columbia Women’s Foundation. Dr. Galea and Hachinski had no relevant disclosures.

A version of this article first appeared on Medscape.com.

A large percentage of studies in neurology and psychiatry over the past decade have failed to account for differences between the sexes, according to a team of Canadian researchers.

In a survey of more than 3,000 papers published in six neuroscience and psychiatry journals from 2009 to 2019, researchers found that only 5% analyzed sex as a variable.

“Despite the fact there are papers that are using males and females in the studies, they’re not using the males and females in the way that would optimally find the possibility of sex differences,” lead author Liisa A.M. Galea, PhD, told this news organization. Dr. Galea is a professor and distinguished scholar at the Djavad Mowafaghian Center for Brain Health at the University of British Columbia in Vancouver.

The study was published online in Nature Communications.
 

Optimal design uncommon

Differences in how neurologic and psychiatric diseases affect men and women have been well documented. Women, for example, are more susceptible to severe stroke, and men are more prone to cognitive decline with schizophrenia. With Alzheimer’s disease, women typically have more severe cognitive defects.

The researchers surveyed 3,193 papers that included a multitude of studies. Although most of the papers reported studies that included both sexes, only 19% of surveyed studies used what Dr. Galea called an optimal design for the discovery of sex differences. “What I mean by ‘optimally’ is the design of the experiments and the analysis of sex as a variable,” she said. And in 2019, only 5% of the studies used sex as a variable for determining differences between the sexes, the study found.

In the current research, two authors read the methods and results of each study described in each paper, Dr. Galea said. The readers noted whether the paper reported the study sample size and whether the studies used a balanced design. The surveyed journals include Nature Neuroscience, Neuron, Journal of Neuroscience, Molecular Psychiatry, Biological Psychiatry, and Neuropsychopharmacology.
 

‘Not much is changing’

“I had a suspicion that this was happening,” Dr. Galea said. “I didn’t know that it’s so bad, to be fair.” The “good news story,” she said, is that more papers considered sex as a factor in the later years surveyed. In 2019, more than 95% of papers across both disciplines reported participants’ sex, compared with about 70% in 2009. However, less than 20% of the papers in all study years reported studies that used sex optimally to determine differences between the sexes.

“The other thing that shocked me,” Dr. Galea said, “was that even despite the fact that we saw this increase in the number of papers that were using males and females, we didn’t see the sort of corresponding increase in those that were using ‘optimal design’ or ‘optimal analysis,’ ” Dr. Galea said. In 2009, 14% of papers used optimal design and 2% used optimal analysis for determining sex differences. By 2019, those percentages were 19% and 5%, respectively.

But even the papers that used both sexes had shortcomings, the study found. Just over one-third of these papers (34.5%) didn’t use a balanced design. Just over one-quarter (25.9%) didn’t identify the sample size, a shortcoming that marked 18% of these studies in 2009 and 33% in 2019. Fifteen percent of papers examined included studies that used both sexes inconsistently.

“That matters, because other studies have found that about 20% of papers are doing some kind of analysis with sex, but we had a suspicion that a lot of studies would include sex as a covariate,” Dr. Galea said. “Essentially what that does is, you remove that variable from the data. So, any statistical variation due to sex is then gone.

“The problem with that,” she added, “is you’re not actually looking to see if there’s an influence of sex; you’re removing it.”

Dr. Galea noted that this study points to a need for funding agencies to demand that researchers meet their mandates on sex- and gender-based analysis. “Despite the mandates, not much is really changing as far as the analysis or design of experiments, and we need to figure out how to change that,” she said. “We need to figure out how to get researchers more interested to use the power of studying sex differences.”
 

‘Not surprising, but disappointing’

Vladimir Hachinski, MD, professor of neurology and epidemiology at Western University in London, Ont., and former editor in chief of Stroke, told this news organization that women have almost twice the life risk of developing dementia, are at higher risk of stroke below age 35 years, and have more severe strokes and higher rates of disability at any age.

Commenting on the current study, Dr. Hachinski said, “It’s not surprising, but it’s disappointing, because we’ve known the difference for a long time.” He added, “The paper is very important because we were not aware that it was that bad.”

Dr. Hachinski also stated, “This paper needs a lot of reading. It’s a great resource, and it should be highlighted as one of those things that needs to be addressed, because it matters.”

The study was funded by a Natural Sciences and Engineering Research Council of Canada grant and by the British Columbia Women’s Foundation. Dr. Galea and Hachinski had no relevant disclosures.

A version of this article first appeared on Medscape.com.

The benefit of endovascular therapy in the treatment of stroke caused by an occlusion of the basilar artery has finally been confirmed in the ATTENTION randomized trial.

The study, conducted in China, showed that endovascular therapy for basilar artery occlusion is associated with higher rates of favorable and independent outcomes, as well as lower overall disability and lower mortality at 90 days, than best medical management alone.

The results were presented by Raul Nogueira, MD, professor of neurology at the University of Pittsburgh School of Medicine, at the European Stroke Organisation Conference (ESOC) 2022, where they were greeted with applause from the audience.

The number needed to treat was just four.

“There were no surprises with secondary endpoints; everything was highly statistically significant,” Dr. Nogueira said.

Specifically, there was a lower rate of overall disability in the shift analysis, with a common odds ratio of 2.8 favoring the intervention.  

Safety results showed an increased risk for symptomatic ICH in the endovascular group (5.3% vs. 0.0%) but, despite that, 90-day mortality was significantly lower in the endovascular group (36.7% vs. 55.3%).

Dr. Nogueira noted a limitation of the study was that it was conducted in China.

“This was a Chinese study and, as Asians are known to have higher rates of intracranial atherosclerotic disease, the overall degree of generalizability of our findings to Western countries needs to be considered,” he commented.

However, subgroup analysis showed no treatment effect modification based on the presence of intracranial atherosclerotic disease, he noted.

Also, the proportion of comorbidities in the ATTENTION trial was similar to that in the BASICS trial, with the same degree of diabetes and atrial fibrillation.

Dr. Nogueira concluded that, in contrast to previous randomized trials of endovascular treatment for basilar artery occlusion, the ATTENTION trial was able to reinforce consecutive enrollment, resulting in a fast recruitment while minimizing crossovers. 

Furthermore, he pointed out that the overall results are consistent with modern era observational studies, large registries, and meta-analysis.

Commenting on the study, Joanna Wardlaw, MD, professor of applied neuroimaging at the University of Edinburgh (Scotland), and chair of the ESOC Planning Group, said: “This is a very important result, since it provides confirmation beyond doubt the benefit of thrombectomy versus medical therapy for basilar artery occlusion stroke up to 12 hours after onset.”

Dr. Wardlaw added: “The trial was large enough to provide clear results and to enable subgroup analyses; no subgroup did not benefit from thrombectomy.”

In a discussion after the presentation, Urs Fischer, MD, chair of the department of neurology at the University Hospital Basel, Switzerland, said he was not surprised by the results of the ATTENTION trial.

“We have been doing thrombectomy in patients with basilar artery occlusion now for 20 years, although trials are extremely important to answer these questions, so now we have some clear evidence,” Dr. Fischer said. “Nevertheless, there are some caveats, as this is an Asian population, but this is a proof of concept, and it is going in the right direction.”

The ATTENTION trial was sponsored by the First Affiliated Hospital of University of Science and Technology of China.

A version of this article first appeared on Medscape.com.

The benefit of endovascular therapy in the treatment of stroke caused by an occlusion of the basilar artery has finally been confirmed in the ATTENTION randomized trial.

The study, conducted in China, showed that endovascular therapy for basilar artery occlusion is associated with higher rates of favorable and independent outcomes, as well as lower overall disability and lower mortality at 90 days, than best medical management alone.

The results were presented by Raul Nogueira, MD, professor of neurology at the University of Pittsburgh School of Medicine, at the European Stroke Organisation Conference (ESOC) 2022, where they were greeted with applause from the audience.

The number needed to treat was just four.

“There were no surprises with secondary endpoints; everything was highly statistically significant,” Dr. Nogueira said.

Specifically, there was a lower rate of overall disability in the shift analysis, with a common odds ratio of 2.8 favoring the intervention.  

Safety results showed an increased risk for symptomatic ICH in the endovascular group (5.3% vs. 0.0%) but, despite that, 90-day mortality was significantly lower in the endovascular group (36.7% vs. 55.3%).

Dr. Nogueira noted a limitation of the study was that it was conducted in China.

“This was a Chinese study and, as Asians are known to have higher rates of intracranial atherosclerotic disease, the overall degree of generalizability of our findings to Western countries needs to be considered,” he commented.

However, subgroup analysis showed no treatment effect modification based on the presence of intracranial atherosclerotic disease, he noted.

Also, the proportion of comorbidities in the ATTENTION trial was similar to that in the BASICS trial, with the same degree of diabetes and atrial fibrillation.

Dr. Nogueira concluded that, in contrast to previous randomized trials of endovascular treatment for basilar artery occlusion, the ATTENTION trial was able to reinforce consecutive enrollment, resulting in a fast recruitment while minimizing crossovers. 

Furthermore, he pointed out that the overall results are consistent with modern era observational studies, large registries, and meta-analysis.

Commenting on the study, Joanna Wardlaw, MD, professor of applied neuroimaging at the University of Edinburgh (Scotland), and chair of the ESOC Planning Group, said: “This is a very important result, since it provides confirmation beyond doubt the benefit of thrombectomy versus medical therapy for basilar artery occlusion stroke up to 12 hours after onset.”

Dr. Wardlaw added: “The trial was large enough to provide clear results and to enable subgroup analyses; no subgroup did not benefit from thrombectomy.”

In a discussion after the presentation, Urs Fischer, MD, chair of the department of neurology at the University Hospital Basel, Switzerland, said he was not surprised by the results of the ATTENTION trial.

“We have been doing thrombectomy in patients with basilar artery occlusion now for 20 years, although trials are extremely important to answer these questions, so now we have some clear evidence,” Dr. Fischer said. “Nevertheless, there are some caveats, as this is an Asian population, but this is a proof of concept, and it is going in the right direction.”

The ATTENTION trial was sponsored by the First Affiliated Hospital of University of Science and Technology of China.

A version of this article first appeared on Medscape.com.

The benefit of endovascular therapy in the treatment of stroke caused by an occlusion of the basilar artery has finally been confirmed in the ATTENTION randomized trial.

The study, conducted in China, showed that endovascular therapy for basilar artery occlusion is associated with higher rates of favorable and independent outcomes, as well as lower overall disability and lower mortality at 90 days, than best medical management alone.

The results were presented by Raul Nogueira, MD, professor of neurology at the University of Pittsburgh School of Medicine, at the European Stroke Organisation Conference (ESOC) 2022, where they were greeted with applause from the audience.

The number needed to treat was just four.

“There were no surprises with secondary endpoints; everything was highly statistically significant,” Dr. Nogueira said.

Specifically, there was a lower rate of overall disability in the shift analysis, with a common odds ratio of 2.8 favoring the intervention.  

Safety results showed an increased risk for symptomatic ICH in the endovascular group (5.3% vs. 0.0%) but, despite that, 90-day mortality was significantly lower in the endovascular group (36.7% vs. 55.3%).

Dr. Nogueira noted a limitation of the study was that it was conducted in China.

“This was a Chinese study and, as Asians are known to have higher rates of intracranial atherosclerotic disease, the overall degree of generalizability of our findings to Western countries needs to be considered,” he commented.

However, subgroup analysis showed no treatment effect modification based on the presence of intracranial atherosclerotic disease, he noted.

Also, the proportion of comorbidities in the ATTENTION trial was similar to that in the BASICS trial, with the same degree of diabetes and atrial fibrillation.

Dr. Nogueira concluded that, in contrast to previous randomized trials of endovascular treatment for basilar artery occlusion, the ATTENTION trial was able to reinforce consecutive enrollment, resulting in a fast recruitment while minimizing crossovers. 

Furthermore, he pointed out that the overall results are consistent with modern era observational studies, large registries, and meta-analysis.

Commenting on the study, Joanna Wardlaw, MD, professor of applied neuroimaging at the University of Edinburgh (Scotland), and chair of the ESOC Planning Group, said: “This is a very important result, since it provides confirmation beyond doubt the benefit of thrombectomy versus medical therapy for basilar artery occlusion stroke up to 12 hours after onset.”

Dr. Wardlaw added: “The trial was large enough to provide clear results and to enable subgroup analyses; no subgroup did not benefit from thrombectomy.”

In a discussion after the presentation, Urs Fischer, MD, chair of the department of neurology at the University Hospital Basel, Switzerland, said he was not surprised by the results of the ATTENTION trial.

“We have been doing thrombectomy in patients with basilar artery occlusion now for 20 years, although trials are extremely important to answer these questions, so now we have some clear evidence,” Dr. Fischer said. “Nevertheless, there are some caveats, as this is an Asian population, but this is a proof of concept, and it is going in the right direction.”

The ATTENTION trial was sponsored by the First Affiliated Hospital of University of Science and Technology of China.

A version of this article first appeared on Medscape.com.

A new study finds clinicians are shifting away from the U.S. Food and Drug Administration–approved combination of warfarin and aspirin after left atrial appendage occlusion (LAAO) with the Watchman device and that adverse events, particularly bleeding, are lower when aspirin is dropped.

Of 31,994 patients successfully implanted with the Watchman 2.5 device in the 3 years after its March 2015 approval, only 1 in 10 received the full postprocedure protocol studied in pivotal trials and codified into the FDA-device approval.

The protocol consisted of aspirin (81-325 mg) indefinitely and warfarin for 45 days. Following transesophageal echocardiography, patients were then maintained on warfarin and aspirin if there was a peridevice leak greater than 5 mm or switched to clopidogrel 75 mg for 6 months if a peridevice leak was ruled out or was 5 mm or less.

Based on the results, drawn from the National Cardiovascular Data Registry (NCDR) LAAO Registry, the most common discharge medications were warfarin and aspirin in 36.9% of patients, followed by a direct oral anticoagulant (DOAC) and aspirin (20.8%), warfarin alone (13.5%), DOAC only (12.3%), and dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor (5%).

“There’s a little bit of practice leading the science in this space,” lead author James V. Freeman, MD, MPH, Yale School of Medicine, New Haven, Conn., told this news organization.

Patients who couldn’t tolerate long-term anticoagulation were excluded from the pivotal trials but are now the patients in whom the device is most often used, because of the Centers for Medicare & Medicaid reimbursement mandate for a relative or absolute contraindication to long-term anticoagulation, he noted.

Not surprisingly, 70% of patients in the registry had history of clinically relevant bleeding, the mean CHA2DS2-VASc score was 4.6, and mean HAS-BLED score was 3. At an average age of 76, they were also older, by years, than those in the clinical trials.

Secular trends at the time also saw the ascendancy of the DOACs relative to warfarin, observed Dr. Freeman. “So I think it’s pretty reasonable for physicians to be considering DOACs rather than warfarin in this context.”
 

Aspirin takes another hit

Results, published May 2 in the Journal of the American College of Cardiology, showed that any adverse event occurred at 45 days in 5.7% of patients discharged on warfarin and aspirin, 4% on warfarin alone, 5.2% on DOAC and aspirin, 3.8% on DOAC only, and 5.5% on DAPT.

Rates of any major adverse event were 4.4%, 3.3%, 4.3%, 3.1%, and 4.2% respectively, and for major bleeding were 3%, 1.8%, 2.8%, 1.7%, and 2.2% respectively. Although patients were similar across treatment groups, those treated with DAPT were slightly older and had more comorbidities, Dr. Freeman said.

In Cox frailty regression, the adjusted risk of any adverse event at 45 days was significantly lower when patients were discharged on warfarin alone (hazard ratio, 0.692; 95% confidence interval, 0.56-0.84) and a DOAC alone (HR, 0.731; 95% CI, 0.57-0.93), compared with warfarin and aspirin. There were no differences among the other groups.

The risk of any major adverse event was also significantly lower with warfarin alone (HR, 0.658; 95% CI, 0.53-0.80) and DOAC alone (HR, 0.767; 95% CI, 0.59-0.98).

At 6 months, rates of any adverse event (HR, 0.814; 95% CI, 0.72-0.93) and any major adverse event (HR, 0.840; 95% CI, 0.73-0.95) were significantly lower only in patients treated with warfarin alone.

“I think if there’s a take-home [message] here, it’s that for a lot of patients there’s good data now to suggest getting rid of the aspirin is a very reasonable thing to do,” Dr. Freeman said.

Further studies are needed in the space, but the results are consistent with those from transcatheter aortic valve replacement studies showing discharge on warfarin or DOAC anticoagulation alone reduces major adverse events without increasing thrombotic events, he said.

“I do think if there’s a strong indication for aspirin – someone has terrible coronary disease – there may be a role for using it,” Dr. Freeman said. But for a lot of these patients, anticoagulation alone without aspirin “may present a big opportunity to mitigate morbidity associated with this procedure.”

Dr. Freeman said he doesn’t expect the findings would be dramatically different with the second-generation Watchman FLX device but noted that randomized data will be forthcoming, as Boston Scientific changed the CHAMPION-AF trial protocol to include DOAC alone without aspirin.

Commenting for this news organization, Domenico Della Rocca, MD, Texas Cardiac Arrhythmia Institute at St. David’s Medical Center, Austin, said the study is a useful overview of post-LAAO therapies in a large population – but not surprising.

“Practice has changed over the years. More and more we are adopting and trusting the DOACs,” he said. “And, we are realizing that dual antiplatelet therapy is so aggressive and antiplatelet therapy alone maybe is not the best choice based on data on activation of coagulation.”

Commenting further, he said “I think it’s too early to suggest being too keen to completely drop aspirin,” noting that 20%-25% of patients have clopidogrel resistance and that the combination of two antiplatelets may be too aggressive a strategy for others.

Dr. Della Rocca and colleagues recently reported favorable long-term results with half-dose DOAC therapy after Watchman implantation and said the team is launching a randomized trial in more than 500 LAAO patients in the United States and Europe later this year. The trial will be comparing a DOAC-based strategy with low-dose apixaban long-term versus clopidogrel and aspirin initially and then switching to 100 mg aspirin long-term.

“We hope that in the next 2-3 years we will have some better answers, but at this point I would say that clopidogrel is kind of an obsolete strategy for appendage closure,” Dr. Della Rocca said.

In an accompanying editorial, David R. Holmes Jr., MD, Mayo Clinic, Rochester, Minn., says “the cornucopia of these specific strategies can be expected to change as practices evolve, as instructions for use broaden and, hopefully, with the results of well-done, scientifically performed trials. This current LAAO Registry report, however, serves as a useful benchmark.”

He cautioned that this is an observational cohort study and that unmeasured imbalances still may affect the ability to identify an unbiased treatment signal. The use of DAPT was also infrequent during the study and “conclusions based on this information are soft.”

The study was funded by the American College of Cardiology National Cardiovascular Data Registry (NCDR), and the National Heart, Lung, and Blood Institute (NHLBI) grants. Dr. Freeman has received salary support from the ACC NCDR and the NHLBI and has received consulting/advisory board fees from Boston Scientific, Medtronic, Janssen Pharmaceuticals, and Biosense Webster.

A version of this article first appeared on Medscape.com.

A new study finds clinicians are shifting away from the U.S. Food and Drug Administration–approved combination of warfarin and aspirin after left atrial appendage occlusion (LAAO) with the Watchman device and that adverse events, particularly bleeding, are lower when aspirin is dropped.

Of 31,994 patients successfully implanted with the Watchman 2.5 device in the 3 years after its March 2015 approval, only 1 in 10 received the full postprocedure protocol studied in pivotal trials and codified into the FDA-device approval.

The protocol consisted of aspirin (81-325 mg) indefinitely and warfarin for 45 days. Following transesophageal echocardiography, patients were then maintained on warfarin and aspirin if there was a peridevice leak greater than 5 mm or switched to clopidogrel 75 mg for 6 months if a peridevice leak was ruled out or was 5 mm or less.

Based on the results, drawn from the National Cardiovascular Data Registry (NCDR) LAAO Registry, the most common discharge medications were warfarin and aspirin in 36.9% of patients, followed by a direct oral anticoagulant (DOAC) and aspirin (20.8%), warfarin alone (13.5%), DOAC only (12.3%), and dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor (5%).

“There’s a little bit of practice leading the science in this space,” lead author James V. Freeman, MD, MPH, Yale School of Medicine, New Haven, Conn., told this news organization.

Patients who couldn’t tolerate long-term anticoagulation were excluded from the pivotal trials but are now the patients in whom the device is most often used, because of the Centers for Medicare & Medicaid reimbursement mandate for a relative or absolute contraindication to long-term anticoagulation, he noted.

Not surprisingly, 70% of patients in the registry had history of clinically relevant bleeding, the mean CHA2DS2-VASc score was 4.6, and mean HAS-BLED score was 3. At an average age of 76, they were also older, by years, than those in the clinical trials.

Secular trends at the time also saw the ascendancy of the DOACs relative to warfarin, observed Dr. Freeman. “So I think it’s pretty reasonable for physicians to be considering DOACs rather than warfarin in this context.”
 

Aspirin takes another hit

Results, published May 2 in the Journal of the American College of Cardiology, showed that any adverse event occurred at 45 days in 5.7% of patients discharged on warfarin and aspirin, 4% on warfarin alone, 5.2% on DOAC and aspirin, 3.8% on DOAC only, and 5.5% on DAPT.

Rates of any major adverse event were 4.4%, 3.3%, 4.3%, 3.1%, and 4.2% respectively, and for major bleeding were 3%, 1.8%, 2.8%, 1.7%, and 2.2% respectively. Although patients were similar across treatment groups, those treated with DAPT were slightly older and had more comorbidities, Dr. Freeman said.

In Cox frailty regression, the adjusted risk of any adverse event at 45 days was significantly lower when patients were discharged on warfarin alone (hazard ratio, 0.692; 95% confidence interval, 0.56-0.84) and a DOAC alone (HR, 0.731; 95% CI, 0.57-0.93), compared with warfarin and aspirin. There were no differences among the other groups.

The risk of any major adverse event was also significantly lower with warfarin alone (HR, 0.658; 95% CI, 0.53-0.80) and DOAC alone (HR, 0.767; 95% CI, 0.59-0.98).

At 6 months, rates of any adverse event (HR, 0.814; 95% CI, 0.72-0.93) and any major adverse event (HR, 0.840; 95% CI, 0.73-0.95) were significantly lower only in patients treated with warfarin alone.

“I think if there’s a take-home [message] here, it’s that for a lot of patients there’s good data now to suggest getting rid of the aspirin is a very reasonable thing to do,” Dr. Freeman said.

Further studies are needed in the space, but the results are consistent with those from transcatheter aortic valve replacement studies showing discharge on warfarin or DOAC anticoagulation alone reduces major adverse events without increasing thrombotic events, he said.

“I do think if there’s a strong indication for aspirin – someone has terrible coronary disease – there may be a role for using it,” Dr. Freeman said. But for a lot of these patients, anticoagulation alone without aspirin “may present a big opportunity to mitigate morbidity associated with this procedure.”

Dr. Freeman said he doesn’t expect the findings would be dramatically different with the second-generation Watchman FLX device but noted that randomized data will be forthcoming, as Boston Scientific changed the CHAMPION-AF trial protocol to include DOAC alone without aspirin.

Commenting for this news organization, Domenico Della Rocca, MD, Texas Cardiac Arrhythmia Institute at St. David’s Medical Center, Austin, said the study is a useful overview of post-LAAO therapies in a large population – but not surprising.

“Practice has changed over the years. More and more we are adopting and trusting the DOACs,” he said. “And, we are realizing that dual antiplatelet therapy is so aggressive and antiplatelet therapy alone maybe is not the best choice based on data on activation of coagulation.”

Commenting further, he said “I think it’s too early to suggest being too keen to completely drop aspirin,” noting that 20%-25% of patients have clopidogrel resistance and that the combination of two antiplatelets may be too aggressive a strategy for others.

Dr. Della Rocca and colleagues recently reported favorable long-term results with half-dose DOAC therapy after Watchman implantation and said the team is launching a randomized trial in more than 500 LAAO patients in the United States and Europe later this year. The trial will be comparing a DOAC-based strategy with low-dose apixaban long-term versus clopidogrel and aspirin initially and then switching to 100 mg aspirin long-term.

“We hope that in the next 2-3 years we will have some better answers, but at this point I would say that clopidogrel is kind of an obsolete strategy for appendage closure,” Dr. Della Rocca said.

In an accompanying editorial, David R. Holmes Jr., MD, Mayo Clinic, Rochester, Minn., says “the cornucopia of these specific strategies can be expected to change as practices evolve, as instructions for use broaden and, hopefully, with the results of well-done, scientifically performed trials. This current LAAO Registry report, however, serves as a useful benchmark.”

He cautioned that this is an observational cohort study and that unmeasured imbalances still may affect the ability to identify an unbiased treatment signal. The use of DAPT was also infrequent during the study and “conclusions based on this information are soft.”

The study was funded by the American College of Cardiology National Cardiovascular Data Registry (NCDR), and the National Heart, Lung, and Blood Institute (NHLBI) grants. Dr. Freeman has received salary support from the ACC NCDR and the NHLBI and has received consulting/advisory board fees from Boston Scientific, Medtronic, Janssen Pharmaceuticals, and Biosense Webster.

A version of this article first appeared on Medscape.com.

A new study finds clinicians are shifting away from the U.S. Food and Drug Administration–approved combination of warfarin and aspirin after left atrial appendage occlusion (LAAO) with the Watchman device and that adverse events, particularly bleeding, are lower when aspirin is dropped.

Of 31,994 patients successfully implanted with the Watchman 2.5 device in the 3 years after its March 2015 approval, only 1 in 10 received the full postprocedure protocol studied in pivotal trials and codified into the FDA-device approval.

The protocol consisted of aspirin (81-325 mg) indefinitely and warfarin for 45 days. Following transesophageal echocardiography, patients were then maintained on warfarin and aspirin if there was a peridevice leak greater than 5 mm or switched to clopidogrel 75 mg for 6 months if a peridevice leak was ruled out or was 5 mm or less.

Based on the results, drawn from the National Cardiovascular Data Registry (NCDR) LAAO Registry, the most common discharge medications were warfarin and aspirin in 36.9% of patients, followed by a direct oral anticoagulant (DOAC) and aspirin (20.8%), warfarin alone (13.5%), DOAC only (12.3%), and dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor (5%).

“There’s a little bit of practice leading the science in this space,” lead author James V. Freeman, MD, MPH, Yale School of Medicine, New Haven, Conn., told this news organization.

Patients who couldn’t tolerate long-term anticoagulation were excluded from the pivotal trials but are now the patients in whom the device is most often used, because of the Centers for Medicare & Medicaid reimbursement mandate for a relative or absolute contraindication to long-term anticoagulation, he noted.

Not surprisingly, 70% of patients in the registry had history of clinically relevant bleeding, the mean CHA2DS2-VASc score was 4.6, and mean HAS-BLED score was 3. At an average age of 76, they were also older, by years, than those in the clinical trials.

Secular trends at the time also saw the ascendancy of the DOACs relative to warfarin, observed Dr. Freeman. “So I think it’s pretty reasonable for physicians to be considering DOACs rather than warfarin in this context.”
 

Aspirin takes another hit

Results, published May 2 in the Journal of the American College of Cardiology, showed that any adverse event occurred at 45 days in 5.7% of patients discharged on warfarin and aspirin, 4% on warfarin alone, 5.2% on DOAC and aspirin, 3.8% on DOAC only, and 5.5% on DAPT.

Rates of any major adverse event were 4.4%, 3.3%, 4.3%, 3.1%, and 4.2% respectively, and for major bleeding were 3%, 1.8%, 2.8%, 1.7%, and 2.2% respectively. Although patients were similar across treatment groups, those treated with DAPT were slightly older and had more comorbidities, Dr. Freeman said.

In Cox frailty regression, the adjusted risk of any adverse event at 45 days was significantly lower when patients were discharged on warfarin alone (hazard ratio, 0.692; 95% confidence interval, 0.56-0.84) and a DOAC alone (HR, 0.731; 95% CI, 0.57-0.93), compared with warfarin and aspirin. There were no differences among the other groups.

The risk of any major adverse event was also significantly lower with warfarin alone (HR, 0.658; 95% CI, 0.53-0.80) and DOAC alone (HR, 0.767; 95% CI, 0.59-0.98).

At 6 months, rates of any adverse event (HR, 0.814; 95% CI, 0.72-0.93) and any major adverse event (HR, 0.840; 95% CI, 0.73-0.95) were significantly lower only in patients treated with warfarin alone.

“I think if there’s a take-home [message] here, it’s that for a lot of patients there’s good data now to suggest getting rid of the aspirin is a very reasonable thing to do,” Dr. Freeman said.

Further studies are needed in the space, but the results are consistent with those from transcatheter aortic valve replacement studies showing discharge on warfarin or DOAC anticoagulation alone reduces major adverse events without increasing thrombotic events, he said.

“I do think if there’s a strong indication for aspirin – someone has terrible coronary disease – there may be a role for using it,” Dr. Freeman said. But for a lot of these patients, anticoagulation alone without aspirin “may present a big opportunity to mitigate morbidity associated with this procedure.”

Dr. Freeman said he doesn’t expect the findings would be dramatically different with the second-generation Watchman FLX device but noted that randomized data will be forthcoming, as Boston Scientific changed the CHAMPION-AF trial protocol to include DOAC alone without aspirin.

Commenting for this news organization, Domenico Della Rocca, MD, Texas Cardiac Arrhythmia Institute at St. David’s Medical Center, Austin, said the study is a useful overview of post-LAAO therapies in a large population – but not surprising.

“Practice has changed over the years. More and more we are adopting and trusting the DOACs,” he said. “And, we are realizing that dual antiplatelet therapy is so aggressive and antiplatelet therapy alone maybe is not the best choice based on data on activation of coagulation.”

Commenting further, he said “I think it’s too early to suggest being too keen to completely drop aspirin,” noting that 20%-25% of patients have clopidogrel resistance and that the combination of two antiplatelets may be too aggressive a strategy for others.

Dr. Della Rocca and colleagues recently reported favorable long-term results with half-dose DOAC therapy after Watchman implantation and said the team is launching a randomized trial in more than 500 LAAO patients in the United States and Europe later this year. The trial will be comparing a DOAC-based strategy with low-dose apixaban long-term versus clopidogrel and aspirin initially and then switching to 100 mg aspirin long-term.

“We hope that in the next 2-3 years we will have some better answers, but at this point I would say that clopidogrel is kind of an obsolete strategy for appendage closure,” Dr. Della Rocca said.

In an accompanying editorial, David R. Holmes Jr., MD, Mayo Clinic, Rochester, Minn., says “the cornucopia of these specific strategies can be expected to change as practices evolve, as instructions for use broaden and, hopefully, with the results of well-done, scientifically performed trials. This current LAAO Registry report, however, serves as a useful benchmark.”

He cautioned that this is an observational cohort study and that unmeasured imbalances still may affect the ability to identify an unbiased treatment signal. The use of DAPT was also infrequent during the study and “conclusions based on this information are soft.”

The study was funded by the American College of Cardiology National Cardiovascular Data Registry (NCDR), and the National Heart, Lung, and Blood Institute (NHLBI) grants. Dr. Freeman has received salary support from the ACC NCDR and the NHLBI and has received consulting/advisory board fees from Boston Scientific, Medtronic, Janssen Pharmaceuticals, and Biosense Webster.

A version of this article first appeared on Medscape.com.

Having had a recent acute febrile illness was associated with an increased risk for ischemic stroke, whereas having received an influenza vaccination was associated with a reduced risk for stroke in a large new case-control study.

“While influenza vaccination is a cost-effective method to prevent influenza, it is also an effective way to reduce the burden of stroke,” said study author Christopher Schwarzbach, MD, of Ludwigshafen (Germany) Hospital.  

“Our results therefore encourage the wider use of influenza vaccination,” he concluded.

Dr. Schwarzbach presented these data from the INTERSTROKE study at the 2022 European Stroke Organisation Conference.

He explained that acute inflammatory disease is thought to increase the risk for cerebrovascular events, and the seasonality of influenza-like illness appears to be associated with the seasonality of cardiovascular and cerebrovascular events. Previous observational studies have also shown a link between influenza vaccination and a reduced risk for stroke.

The current INTERSTROKE study was a large international case-control study conducted between 2007 and 2015 that involved 13,447 cases (patients within 5 days of their first stroke) and a similar number of age- and gender-matched people from 32 countries across the world.

All cases and control subjects were systematically asked whether they had acute febrile illness in the previous 4 weeks and whether they had received an influenza vaccination within the previous year.

Conditional logistical regression was used to quantify the results, with adjustment for 13 different possible confounding factors, including hypertension, activity, smoking, cardiovascular risk factors, and socioeconomic factors.

Results showed that having had an acute febrile illness in the previous 4 weeks was more commonly reported in the patients with an acute ischemic stroke (8.7%) than in control patients (5.6%). After adjustment for confounding factors, this gives an adjusted risk ratio of 1.18, which was of borderline statistical significance (95% confidence limits, 1.01-1.39), Dr. Schwarzbach reported.

The association between recent febrile illness and acute ischemic stroke was stronger when compared with community control subjects (adjusted odds ratio, 2.0), but it was absent when compared with hospital control subjects.

The association was also only apparent in Australia, China, North America, and Western Europe; it was not seen in other parts of the world.

There was no association between acute febrile illness and acute cerebral hemorrhage.
 

Flu vaccine linked to halving of stroke risk

Having received a flu vaccine in the previous year was strongly associated with a lower risk for any type of stroke (aOR, 0.53), ischemic stroke (aOR, 0.57), and hemorrhagic stroke (aOR, 0.34).

Dr. Schwarzbach noted that these results were also consistent in an extended statistical model that included variables that might reflect a willingness to be vaccinated and when compared with both community and hospital-based control subjects.

The strength of the association between influenza vaccination and reduced risk for stroke was similar when compared with either community or hospital control subjects, and was only moderately stronger during than outside the influenza season.

The association was also seen in all regions of the world apart from Africa and South Asia, Dr. Schwarzbach reported, but he noted that vaccination rates in these two regions were extremely low.  

The researchers also found that the magnitude of the associations between flu vaccination and lower risk for stroke were stronger in individuals who had multiple annual vaccinations, with an odds ratio of 0.54 in those who had received a vaccine every year for the previous 5 years, and of 0.79 in those who had received one to four vaccinations in the previous 5 years.
 

Mechanism: Immune stimulation?

Discussing possible mechanisms behind these results, Dr. Schwarzbach noted that the finding that the association with influenza vaccination and reduced stroke risk was independent of seasonality was surprising. “We had expected the protective effect of vaccination to be bigger during the influenza season, but this wasn’t the case.”

He suggested that one explanation might be the inclusion of regions of the world where this seasonality doesn’t exist.

But he pointed out that the finding of a stronger association between flu vaccination and lower stroke risk in those who had received more vaccinations has given rise to another theory: that it is the stimulation of the immune system rather than the protection of infection against influenza that is the key factor.

In an interview with Dr. Schwarzbach, Guillaume Turk, MD, professor of neurology at GHU Paris, pointed out that causal inferences are always difficult in case-control studies and in clinical epidemiology in general.

“What makes you think that this association between influenza vaccination and decreased risk is causal rather than due to unmeasured confounders? For example, patients who received vaccination may have received more medical attention and may have been more aware of the risk factors for stroke,” he asked.  

Dr. Schwarzbach replied: “Yes, this is the issue of healthy user bias, which is always a problem in this type of research and is hard to address.”

“What we tried to do here is to adjust for variables that might influence the willingness of people to get vaccinated,” he added. “These were mainly socioeconomic factors. But, of course, this is something that we can’t rule out.”

Dr. Schwarzbach noted that, for more reliable information on this association, prospective studies are needed.
 

‘A plausible effect’

Discussing the study after the presentation, William Whiteley, BM, PhD, a clinical epidemiologist at the University of Edinburgh and a consultant neurologist in NHS Lothian, said vaccination was a potentially important way to reduce stroke.

“In this study, there was a plausible effect on reducing stroke incidence from vaccination against influenza, and also a plausible increase in the risk of stroke from having a recent febrile illness, which we have seen in other studies,” he commented.

Dr. Whiteley noted that this observation was particularly relevant now because of the COVID-19 pandemic.

“We’ve all been worried about the risk of heart attack and stroke after COVID, where we’ve seen quite early high risks, and we are also optimistic about the effect of vaccination on reducing those incidences. We’ve seen data from the U.K. that there may be around a 20% reduction in risk of stroke from vaccination. So, it’s all quite plausible, but at the moment it’s all based on observational evidence and we really need some randomized evidence,” he said.  

“Vaccination and infections have all sorts of odd confounders,” he added. “People who get vaccines tend to be more healthy than those who don’t get vaccines, so you can start to see quite implausible effects of vaccination on overall mortality, which probably aren’t real, and you probably can’t get rid of that totally with statistical methods.”

Alastair Webb, MD, University of Oxford (England), asked how reliable the current findings were, given that the occurrence of febrile illnesses and receipt of vaccines were all self-reported, and although there was an association for ischemic stroke and febrile illness, this seemed to go in the opposite direction for hemorrhagic stroke. He also noted that the 50% reduction in stroke risk with vaccination in this study seemed “quite a large magnitude of effect.”

Dr. Whiteley replied: “Yes, it is large, but it is promising.” He cited a previous meta-analysis of randomized studies that showed a roughly 25%-35% reduction in vascular events after flu vaccination, but noted that there was a lot of heterogeneity between studies.

“I’m not sure we’re going to see much more randomized evidence, but I think we can probably all agree that having a vaccine against flu or COVID is a good thing for all of us,” Dr. Whiteley concluded.

The INTERSTROKE study was funded by the Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Canadian Stroke Network, Health Research Board Ireland, Swedish Research Council, Swedish Heart and Lung Foundation, The Health & Medical Care Committee of the Regional Executive Board, Region Vastra Gotaland (Sweden), AstraZeneca, Boehringer Ingelheim, Pfizer, MSD, Chest, Heart and Stroke Scotland, and The Stroke Association, with support from The UK Stroke Research Network. The authors reported no relevant disclosures.

A version of this article first appeared on Medscape.com.

Having had a recent acute febrile illness was associated with an increased risk for ischemic stroke, whereas having received an influenza vaccination was associated with a reduced risk for stroke in a large new case-control study.

“While influenza vaccination is a cost-effective method to prevent influenza, it is also an effective way to reduce the burden of stroke,” said study author Christopher Schwarzbach, MD, of Ludwigshafen (Germany) Hospital.  

“Our results therefore encourage the wider use of influenza vaccination,” he concluded.

Dr. Schwarzbach presented these data from the INTERSTROKE study at the 2022 European Stroke Organisation Conference.

He explained that acute inflammatory disease is thought to increase the risk for cerebrovascular events, and the seasonality of influenza-like illness appears to be associated with the seasonality of cardiovascular and cerebrovascular events. Previous observational studies have also shown a link between influenza vaccination and a reduced risk for stroke.

The current INTERSTROKE study was a large international case-control study conducted between 2007 and 2015 that involved 13,447 cases (patients within 5 days of their first stroke) and a similar number of age- and gender-matched people from 32 countries across the world.

All cases and control subjects were systematically asked whether they had acute febrile illness in the previous 4 weeks and whether they had received an influenza vaccination within the previous year.

Conditional logistical regression was used to quantify the results, with adjustment for 13 different possible confounding factors, including hypertension, activity, smoking, cardiovascular risk factors, and socioeconomic factors.

Results showed that having had an acute febrile illness in the previous 4 weeks was more commonly reported in the patients with an acute ischemic stroke (8.7%) than in control patients (5.6%). After adjustment for confounding factors, this gives an adjusted risk ratio of 1.18, which was of borderline statistical significance (95% confidence limits, 1.01-1.39), Dr. Schwarzbach reported.

The association between recent febrile illness and acute ischemic stroke was stronger when compared with community control subjects (adjusted odds ratio, 2.0), but it was absent when compared with hospital control subjects.

The association was also only apparent in Australia, China, North America, and Western Europe; it was not seen in other parts of the world.

There was no association between acute febrile illness and acute cerebral hemorrhage.
 

Flu vaccine linked to halving of stroke risk

Having received a flu vaccine in the previous year was strongly associated with a lower risk for any type of stroke (aOR, 0.53), ischemic stroke (aOR, 0.57), and hemorrhagic stroke (aOR, 0.34).

Dr. Schwarzbach noted that these results were also consistent in an extended statistical model that included variables that might reflect a willingness to be vaccinated and when compared with both community and hospital-based control subjects.

The strength of the association between influenza vaccination and reduced risk for stroke was similar when compared with either community or hospital control subjects, and was only moderately stronger during than outside the influenza season.

The association was also seen in all regions of the world apart from Africa and South Asia, Dr. Schwarzbach reported, but he noted that vaccination rates in these two regions were extremely low.  

The researchers also found that the magnitude of the associations between flu vaccination and lower risk for stroke were stronger in individuals who had multiple annual vaccinations, with an odds ratio of 0.54 in those who had received a vaccine every year for the previous 5 years, and of 0.79 in those who had received one to four vaccinations in the previous 5 years.
 

Mechanism: Immune stimulation?

Discussing possible mechanisms behind these results, Dr. Schwarzbach noted that the finding that the association with influenza vaccination and reduced stroke risk was independent of seasonality was surprising. “We had expected the protective effect of vaccination to be bigger during the influenza season, but this wasn’t the case.”

He suggested that one explanation might be the inclusion of regions of the world where this seasonality doesn’t exist.

But he pointed out that the finding of a stronger association between flu vaccination and lower stroke risk in those who had received more vaccinations has given rise to another theory: that it is the stimulation of the immune system rather than the protection of infection against influenza that is the key factor.

In an interview with Dr. Schwarzbach, Guillaume Turk, MD, professor of neurology at GHU Paris, pointed out that causal inferences are always difficult in case-control studies and in clinical epidemiology in general.

“What makes you think that this association between influenza vaccination and decreased risk is causal rather than due to unmeasured confounders? For example, patients who received vaccination may have received more medical attention and may have been more aware of the risk factors for stroke,” he asked.  

Dr. Schwarzbach replied: “Yes, this is the issue of healthy user bias, which is always a problem in this type of research and is hard to address.”

“What we tried to do here is to adjust for variables that might influence the willingness of people to get vaccinated,” he added. “These were mainly socioeconomic factors. But, of course, this is something that we can’t rule out.”

Dr. Schwarzbach noted that, for more reliable information on this association, prospective studies are needed.
 

‘A plausible effect’

Discussing the study after the presentation, William Whiteley, BM, PhD, a clinical epidemiologist at the University of Edinburgh and a consultant neurologist in NHS Lothian, said vaccination was a potentially important way to reduce stroke.

“In this study, there was a plausible effect on reducing stroke incidence from vaccination against influenza, and also a plausible increase in the risk of stroke from having a recent febrile illness, which we have seen in other studies,” he commented.

Dr. Whiteley noted that this observation was particularly relevant now because of the COVID-19 pandemic.

“We’ve all been worried about the risk of heart attack and stroke after COVID, where we’ve seen quite early high risks, and we are also optimistic about the effect of vaccination on reducing those incidences. We’ve seen data from the U.K. that there may be around a 20% reduction in risk of stroke from vaccination. So, it’s all quite plausible, but at the moment it’s all based on observational evidence and we really need some randomized evidence,” he said.  

“Vaccination and infections have all sorts of odd confounders,” he added. “People who get vaccines tend to be more healthy than those who don’t get vaccines, so you can start to see quite implausible effects of vaccination on overall mortality, which probably aren’t real, and you probably can’t get rid of that totally with statistical methods.”

Alastair Webb, MD, University of Oxford (England), asked how reliable the current findings were, given that the occurrence of febrile illnesses and receipt of vaccines were all self-reported, and although there was an association for ischemic stroke and febrile illness, this seemed to go in the opposite direction for hemorrhagic stroke. He also noted that the 50% reduction in stroke risk with vaccination in this study seemed “quite a large magnitude of effect.”

Dr. Whiteley replied: “Yes, it is large, but it is promising.” He cited a previous meta-analysis of randomized studies that showed a roughly 25%-35% reduction in vascular events after flu vaccination, but noted that there was a lot of heterogeneity between studies.

“I’m not sure we’re going to see much more randomized evidence, but I think we can probably all agree that having a vaccine against flu or COVID is a good thing for all of us,” Dr. Whiteley concluded.

The INTERSTROKE study was funded by the Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Canadian Stroke Network, Health Research Board Ireland, Swedish Research Council, Swedish Heart and Lung Foundation, The Health & Medical Care Committee of the Regional Executive Board, Region Vastra Gotaland (Sweden), AstraZeneca, Boehringer Ingelheim, Pfizer, MSD, Chest, Heart and Stroke Scotland, and The Stroke Association, with support from The UK Stroke Research Network. The authors reported no relevant disclosures.

A version of this article first appeared on Medscape.com.

Having had a recent acute febrile illness was associated with an increased risk for ischemic stroke, whereas having received an influenza vaccination was associated with a reduced risk for stroke in a large new case-control study.

“While influenza vaccination is a cost-effective method to prevent influenza, it is also an effective way to reduce the burden of stroke,” said study author Christopher Schwarzbach, MD, of Ludwigshafen (Germany) Hospital.  

“Our results therefore encourage the wider use of influenza vaccination,” he concluded.

Dr. Schwarzbach presented these data from the INTERSTROKE study at the 2022 European Stroke Organisation Conference.

He explained that acute inflammatory disease is thought to increase the risk for cerebrovascular events, and the seasonality of influenza-like illness appears to be associated with the seasonality of cardiovascular and cerebrovascular events. Previous observational studies have also shown a link between influenza vaccination and a reduced risk for stroke.

The current INTERSTROKE study was a large international case-control study conducted between 2007 and 2015 that involved 13,447 cases (patients within 5 days of their first stroke) and a similar number of age- and gender-matched people from 32 countries across the world.

All cases and control subjects were systematically asked whether they had acute febrile illness in the previous 4 weeks and whether they had received an influenza vaccination within the previous year.

Conditional logistical regression was used to quantify the results, with adjustment for 13 different possible confounding factors, including hypertension, activity, smoking, cardiovascular risk factors, and socioeconomic factors.

Results showed that having had an acute febrile illness in the previous 4 weeks was more commonly reported in the patients with an acute ischemic stroke (8.7%) than in control patients (5.6%). After adjustment for confounding factors, this gives an adjusted risk ratio of 1.18, which was of borderline statistical significance (95% confidence limits, 1.01-1.39), Dr. Schwarzbach reported.

The association between recent febrile illness and acute ischemic stroke was stronger when compared with community control subjects (adjusted odds ratio, 2.0), but it was absent when compared with hospital control subjects.

The association was also only apparent in Australia, China, North America, and Western Europe; it was not seen in other parts of the world.

There was no association between acute febrile illness and acute cerebral hemorrhage.
 

Flu vaccine linked to halving of stroke risk

Having received a flu vaccine in the previous year was strongly associated with a lower risk for any type of stroke (aOR, 0.53), ischemic stroke (aOR, 0.57), and hemorrhagic stroke (aOR, 0.34).

Dr. Schwarzbach noted that these results were also consistent in an extended statistical model that included variables that might reflect a willingness to be vaccinated and when compared with both community and hospital-based control subjects.

The strength of the association between influenza vaccination and reduced risk for stroke was similar when compared with either community or hospital control subjects, and was only moderately stronger during than outside the influenza season.

The association was also seen in all regions of the world apart from Africa and South Asia, Dr. Schwarzbach reported, but he noted that vaccination rates in these two regions were extremely low.  

The researchers also found that the magnitude of the associations between flu vaccination and lower risk for stroke were stronger in individuals who had multiple annual vaccinations, with an odds ratio of 0.54 in those who had received a vaccine every year for the previous 5 years, and of 0.79 in those who had received one to four vaccinations in the previous 5 years.
 

Mechanism: Immune stimulation?

Discussing possible mechanisms behind these results, Dr. Schwarzbach noted that the finding that the association with influenza vaccination and reduced stroke risk was independent of seasonality was surprising. “We had expected the protective effect of vaccination to be bigger during the influenza season, but this wasn’t the case.”

He suggested that one explanation might be the inclusion of regions of the world where this seasonality doesn’t exist.

But he pointed out that the finding of a stronger association between flu vaccination and lower stroke risk in those who had received more vaccinations has given rise to another theory: that it is the stimulation of the immune system rather than the protection of infection against influenza that is the key factor.

In an interview with Dr. Schwarzbach, Guillaume Turk, MD, professor of neurology at GHU Paris, pointed out that causal inferences are always difficult in case-control studies and in clinical epidemiology in general.

“What makes you think that this association between influenza vaccination and decreased risk is causal rather than due to unmeasured confounders? For example, patients who received vaccination may have received more medical attention and may have been more aware of the risk factors for stroke,” he asked.  

Dr. Schwarzbach replied: “Yes, this is the issue of healthy user bias, which is always a problem in this type of research and is hard to address.”

“What we tried to do here is to adjust for variables that might influence the willingness of people to get vaccinated,” he added. “These were mainly socioeconomic factors. But, of course, this is something that we can’t rule out.”

Dr. Schwarzbach noted that, for more reliable information on this association, prospective studies are needed.
 

‘A plausible effect’

Discussing the study after the presentation, William Whiteley, BM, PhD, a clinical epidemiologist at the University of Edinburgh and a consultant neurologist in NHS Lothian, said vaccination was a potentially important way to reduce stroke.

“In this study, there was a plausible effect on reducing stroke incidence from vaccination against influenza, and also a plausible increase in the risk of stroke from having a recent febrile illness, which we have seen in other studies,” he commented.

Dr. Whiteley noted that this observation was particularly relevant now because of the COVID-19 pandemic.

“We’ve all been worried about the risk of heart attack and stroke after COVID, where we’ve seen quite early high risks, and we are also optimistic about the effect of vaccination on reducing those incidences. We’ve seen data from the U.K. that there may be around a 20% reduction in risk of stroke from vaccination. So, it’s all quite plausible, but at the moment it’s all based on observational evidence and we really need some randomized evidence,” he said.  

“Vaccination and infections have all sorts of odd confounders,” he added. “People who get vaccines tend to be more healthy than those who don’t get vaccines, so you can start to see quite implausible effects of vaccination on overall mortality, which probably aren’t real, and you probably can’t get rid of that totally with statistical methods.”

Alastair Webb, MD, University of Oxford (England), asked how reliable the current findings were, given that the occurrence of febrile illnesses and receipt of vaccines were all self-reported, and although there was an association for ischemic stroke and febrile illness, this seemed to go in the opposite direction for hemorrhagic stroke. He also noted that the 50% reduction in stroke risk with vaccination in this study seemed “quite a large magnitude of effect.”

Dr. Whiteley replied: “Yes, it is large, but it is promising.” He cited a previous meta-analysis of randomized studies that showed a roughly 25%-35% reduction in vascular events after flu vaccination, but noted that there was a lot of heterogeneity between studies.

“I’m not sure we’re going to see much more randomized evidence, but I think we can probably all agree that having a vaccine against flu or COVID is a good thing for all of us,” Dr. Whiteley concluded.

The INTERSTROKE study was funded by the Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Canadian Stroke Network, Health Research Board Ireland, Swedish Research Council, Swedish Heart and Lung Foundation, The Health & Medical Care Committee of the Regional Executive Board, Region Vastra Gotaland (Sweden), AstraZeneca, Boehringer Ingelheim, Pfizer, MSD, Chest, Heart and Stroke Scotland, and The Stroke Association, with support from The UK Stroke Research Network. The authors reported no relevant disclosures.

A version of this article first appeared on Medscape.com.

Mild traumatic brain injury (TBI) is linked to a significantly increased risk for a host of subsequent cardiovascular, endocrine, neurologic, and psychiatric disorders, new research shows.

Incidence of hypertension, coronary heart disease, diabetes, stroke, depression, and dementia all began to increase soon after the brain injury and persisted over a decade in both mild and moderate to severe TBI.

Researchers found the multisystem comorbidities in all age groups, including in patients as young as 18. They also found that patients who developed multiple postinjury problems had higher mortality during the decade-long follow-up.

The findings suggest patients with TBI may require longer follow-up and proactive screening for multisystem disease, regardless of age or injury severity.

“The fact that both patients with mild and moderate to severe injuries both had long-term ongoing associations with comorbidities that continued over time and that they are cardiovascular, endocrine, neurologic, and behavioral health oriented was pretty striking,” study author Ross Zafonte, DO, PhD, president of Spaulding Rehab Hospital and professor and chair of physical medicine and rehab at Harvard Medical School, both in Boston, told this news organization.

The study was published online in JAMA Network Open.
 

Injury severity not a factor

An estimated 2.8 million individuals in the United States experience TBI every year. Worldwide, the figure may be as high as 74 million.

Studies have long suggested a link between brain injury and subsequent neurologic disorders, but research suggesting a possible link to cardiovascular and endocrine problems has recently gained attention.

Building on a 2021 study that showed increased incidence of cardiovascular issues following a concussion, the researchers examined medical records of previously healthy patients treated for TBI between 2000 and 2015 who also had at least 1 follow-up visit between 6 months and 10 years after the initial injury.

Researchers analyzed data from 13,053 individuals – 4,351 with mild injury (mTBI), 4351 with moderate to severe injury (msTBI), and 4351 with no TBI. The most common cause of injury was a fall. Patients with sports-related injuries were excluded.

Incidence of hypertension was significantly higher among patients with mTBI (hazard ratio, 2.5; 95% confidence interval, 2.1-2.9) and msTBI (HR, 2.4; 95% CI, 2.0-2.9), compared with the unaffected group. Risk for other cardiovascular problems, including hyperlipidemia, obesity, and coronary artery disease, were also higher in the affected groups.

TBI patients also reported higher incidence of endocrine diseases, including diabetes (mTBI: HR, 1.9; 95% CI, 1.4-2.7; msTBI: HR, 1.9; 95% CI, 1.4-2.6). Elevated risk for ischemic stroke or transient ischemic attack was also increased (mTBI: HR, 2.2; 95% CI, 1.4-3.3; msTBI: HR, 3.6; 95% CI, 2.4-5.3).

Regardless of injury severity, patients with TBI had a higher risk for neurologic and psychiatric diseases, particularly depression, dementia, and psychotic disorders. “This tells us that mild TBI is not clean of events,” Dr. Zafonte said.

Surprising rate of comorbidity in youth

Investigators found increased risk for posttrauma comorbidities in all age groups, but researchers were struck by the high rates in younger patients, aged 18-40. Compared with age-matched individuals with no TBI history, hypertension risk was nearly six times higher in those with mTBI (HR, 5.9; 95% CI, 3.9-9.1) and nearly four times higher in patients with msTBI (HR, 3.9; 95% CI, 2.5-6.1).

Rates of hyperlipidemia and diabetes were also higher in younger patients in the mTBI group and posttraumatic seizures and psychiatric disorders were elevated regardless of TBI severity.

Overall, patients with msTBI, but not those with mTBI, were at higher risk for mortality, compared with the unexposed group (432 deaths [9.9%] vs. 250 deaths [5.7%]; P < .001).

“It’s clear that what we may be dealing with is that it holds up even for the younger people,” Dr. Zafonte said. “We used to think brain injury risk is worse in the severe cases, which it is, and it’s worse later on among those who are older, which it is. But our younger folks don’t get away either.”

While the study offers associations between TBI and multisystem health problems, Dr. Zafonte said it’s impossible to say at this point whether the brain injury caused the increased risk for cardiovascular or endocrine problems. Other organ injuries sustained in the trauma may be a contributing factor.

“Further data is needed to elucidate the mechanism and the causative relationships, which we do not have here,” he said.

Many of the postinjury comorbidities emerged a median of 3.5 years after TBI, regardless of severity. But some of the cardiovascular and psychiatric conditions emerged far sooner than that.

That’s important because research suggests less than half of patients with TBI receive follow-up care.

“It does make sense for folks who are interacting with people who’ve had a TBI to be suspicious of medical comorbidities relatively early on, within the first couple of years,” Dr. Zafonte said.

In an invited commentary, Vijay Krishnamoorthy, MD, MPH, PhD, Duke University, Durham, N.C., and Monica S. Vavilala, MD, University of Washington, Seattle, highlight some of the study’s limitations, including a lack of information on comorbidity severity and the lack of a matched group of patients who experienced non-head trauma.

Despite those limitations, the study offers important information on how TBI may affect organs beyond the brain, they noted.

“These observations, if replicated in future studies, raise intriguing implications in the future care of patients with TBI, including heightened chronic disease-screening measures and possibly enhanced guidelines for chronic extracranial organ system care for patients who experience TBI,” Dr. Krishnamoorthy and Dr. Vavilala wrote.

The study received no specific funding. Dr. Zafonte reported having received personal fees from Springer/Demos, serving on scientific advisory boards for Myomo and OnCare and has received funding from the Football Players Health Study at Harvard, funded in part by the National Football League Players Association. Dr. Krishnamoorthy and Dr. Vavilala disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Mild traumatic brain injury (TBI) is linked to a significantly increased risk for a host of subsequent cardiovascular, endocrine, neurologic, and psychiatric disorders, new research shows.

Incidence of hypertension, coronary heart disease, diabetes, stroke, depression, and dementia all began to increase soon after the brain injury and persisted over a decade in both mild and moderate to severe TBI.

Researchers found the multisystem comorbidities in all age groups, including in patients as young as 18. They also found that patients who developed multiple postinjury problems had higher mortality during the decade-long follow-up.

The findings suggest patients with TBI may require longer follow-up and proactive screening for multisystem disease, regardless of age or injury severity.

“The fact that both patients with mild and moderate to severe injuries both had long-term ongoing associations with comorbidities that continued over time and that they are cardiovascular, endocrine, neurologic, and behavioral health oriented was pretty striking,” study author Ross Zafonte, DO, PhD, president of Spaulding Rehab Hospital and professor and chair of physical medicine and rehab at Harvard Medical School, both in Boston, told this news organization.

The study was published online in JAMA Network Open.
 

Injury severity not a factor

An estimated 2.8 million individuals in the United States experience TBI every year. Worldwide, the figure may be as high as 74 million.

Studies have long suggested a link between brain injury and subsequent neurologic disorders, but research suggesting a possible link to cardiovascular and endocrine problems has recently gained attention.

Building on a 2021 study that showed increased incidence of cardiovascular issues following a concussion, the researchers examined medical records of previously healthy patients treated for TBI between 2000 and 2015 who also had at least 1 follow-up visit between 6 months and 10 years after the initial injury.

Researchers analyzed data from 13,053 individuals – 4,351 with mild injury (mTBI), 4351 with moderate to severe injury (msTBI), and 4351 with no TBI. The most common cause of injury was a fall. Patients with sports-related injuries were excluded.

Incidence of hypertension was significantly higher among patients with mTBI (hazard ratio, 2.5; 95% confidence interval, 2.1-2.9) and msTBI (HR, 2.4; 95% CI, 2.0-2.9), compared with the unaffected group. Risk for other cardiovascular problems, including hyperlipidemia, obesity, and coronary artery disease, were also higher in the affected groups.

TBI patients also reported higher incidence of endocrine diseases, including diabetes (mTBI: HR, 1.9; 95% CI, 1.4-2.7; msTBI: HR, 1.9; 95% CI, 1.4-2.6). Elevated risk for ischemic stroke or transient ischemic attack was also increased (mTBI: HR, 2.2; 95% CI, 1.4-3.3; msTBI: HR, 3.6; 95% CI, 2.4-5.3).

Regardless of injury severity, patients with TBI had a higher risk for neurologic and psychiatric diseases, particularly depression, dementia, and psychotic disorders. “This tells us that mild TBI is not clean of events,” Dr. Zafonte said.

Surprising rate of comorbidity in youth

Investigators found increased risk for posttrauma comorbidities in all age groups, but researchers were struck by the high rates in younger patients, aged 18-40. Compared with age-matched individuals with no TBI history, hypertension risk was nearly six times higher in those with mTBI (HR, 5.9; 95% CI, 3.9-9.1) and nearly four times higher in patients with msTBI (HR, 3.9; 95% CI, 2.5-6.1).

Rates of hyperlipidemia and diabetes were also higher in younger patients in the mTBI group and posttraumatic seizures and psychiatric disorders were elevated regardless of TBI severity.

Overall, patients with msTBI, but not those with mTBI, were at higher risk for mortality, compared with the unexposed group (432 deaths [9.9%] vs. 250 deaths [5.7%]; P < .001).

“It’s clear that what we may be dealing with is that it holds up even for the younger people,” Dr. Zafonte said. “We used to think brain injury risk is worse in the severe cases, which it is, and it’s worse later on among those who are older, which it is. But our younger folks don’t get away either.”

While the study offers associations between TBI and multisystem health problems, Dr. Zafonte said it’s impossible to say at this point whether the brain injury caused the increased risk for cardiovascular or endocrine problems. Other organ injuries sustained in the trauma may be a contributing factor.

“Further data is needed to elucidate the mechanism and the causative relationships, which we do not have here,” he said.

Many of the postinjury comorbidities emerged a median of 3.5 years after TBI, regardless of severity. But some of the cardiovascular and psychiatric conditions emerged far sooner than that.

That’s important because research suggests less than half of patients with TBI receive follow-up care.

“It does make sense for folks who are interacting with people who’ve had a TBI to be suspicious of medical comorbidities relatively early on, within the first couple of years,” Dr. Zafonte said.

In an invited commentary, Vijay Krishnamoorthy, MD, MPH, PhD, Duke University, Durham, N.C., and Monica S. Vavilala, MD, University of Washington, Seattle, highlight some of the study’s limitations, including a lack of information on comorbidity severity and the lack of a matched group of patients who experienced non-head trauma.

Despite those limitations, the study offers important information on how TBI may affect organs beyond the brain, they noted.

“These observations, if replicated in future studies, raise intriguing implications in the future care of patients with TBI, including heightened chronic disease-screening measures and possibly enhanced guidelines for chronic extracranial organ system care for patients who experience TBI,” Dr. Krishnamoorthy and Dr. Vavilala wrote.

The study received no specific funding. Dr. Zafonte reported having received personal fees from Springer/Demos, serving on scientific advisory boards for Myomo and OnCare and has received funding from the Football Players Health Study at Harvard, funded in part by the National Football League Players Association. Dr. Krishnamoorthy and Dr. Vavilala disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Mild traumatic brain injury (TBI) is linked to a significantly increased risk for a host of subsequent cardiovascular, endocrine, neurologic, and psychiatric disorders, new research shows.

Incidence of hypertension, coronary heart disease, diabetes, stroke, depression, and dementia all began to increase soon after the brain injury and persisted over a decade in both mild and moderate to severe TBI.

Researchers found the multisystem comorbidities in all age groups, including in patients as young as 18. They also found that patients who developed multiple postinjury problems had higher mortality during the decade-long follow-up.

The findings suggest patients with TBI may require longer follow-up and proactive screening for multisystem disease, regardless of age or injury severity.

“The fact that both patients with mild and moderate to severe injuries both had long-term ongoing associations with comorbidities that continued over time and that they are cardiovascular, endocrine, neurologic, and behavioral health oriented was pretty striking,” study author Ross Zafonte, DO, PhD, president of Spaulding Rehab Hospital and professor and chair of physical medicine and rehab at Harvard Medical School, both in Boston, told this news organization.

The study was published online in JAMA Network Open.
 

Injury severity not a factor

An estimated 2.8 million individuals in the United States experience TBI every year. Worldwide, the figure may be as high as 74 million.

Studies have long suggested a link between brain injury and subsequent neurologic disorders, but research suggesting a possible link to cardiovascular and endocrine problems has recently gained attention.

Building on a 2021 study that showed increased incidence of cardiovascular issues following a concussion, the researchers examined medical records of previously healthy patients treated for TBI between 2000 and 2015 who also had at least 1 follow-up visit between 6 months and 10 years after the initial injury.

Researchers analyzed data from 13,053 individuals – 4,351 with mild injury (mTBI), 4351 with moderate to severe injury (msTBI), and 4351 with no TBI. The most common cause of injury was a fall. Patients with sports-related injuries were excluded.

Incidence of hypertension was significantly higher among patients with mTBI (hazard ratio, 2.5; 95% confidence interval, 2.1-2.9) and msTBI (HR, 2.4; 95% CI, 2.0-2.9), compared with the unaffected group. Risk for other cardiovascular problems, including hyperlipidemia, obesity, and coronary artery disease, were also higher in the affected groups.

TBI patients also reported higher incidence of endocrine diseases, including diabetes (mTBI: HR, 1.9; 95% CI, 1.4-2.7; msTBI: HR, 1.9; 95% CI, 1.4-2.6). Elevated risk for ischemic stroke or transient ischemic attack was also increased (mTBI: HR, 2.2; 95% CI, 1.4-3.3; msTBI: HR, 3.6; 95% CI, 2.4-5.3).

Regardless of injury severity, patients with TBI had a higher risk for neurologic and psychiatric diseases, particularly depression, dementia, and psychotic disorders. “This tells us that mild TBI is not clean of events,” Dr. Zafonte said.

Surprising rate of comorbidity in youth

Investigators found increased risk for posttrauma comorbidities in all age groups, but researchers were struck by the high rates in younger patients, aged 18-40. Compared with age-matched individuals with no TBI history, hypertension risk was nearly six times higher in those with mTBI (HR, 5.9; 95% CI, 3.9-9.1) and nearly four times higher in patients with msTBI (HR, 3.9; 95% CI, 2.5-6.1).

Rates of hyperlipidemia and diabetes were also higher in younger patients in the mTBI group and posttraumatic seizures and psychiatric disorders were elevated regardless of TBI severity.

Overall, patients with msTBI, but not those with mTBI, were at higher risk for mortality, compared with the unexposed group (432 deaths [9.9%] vs. 250 deaths [5.7%]; P < .001).

“It’s clear that what we may be dealing with is that it holds up even for the younger people,” Dr. Zafonte said. “We used to think brain injury risk is worse in the severe cases, which it is, and it’s worse later on among those who are older, which it is. But our younger folks don’t get away either.”

While the study offers associations between TBI and multisystem health problems, Dr. Zafonte said it’s impossible to say at this point whether the brain injury caused the increased risk for cardiovascular or endocrine problems. Other organ injuries sustained in the trauma may be a contributing factor.

“Further data is needed to elucidate the mechanism and the causative relationships, which we do not have here,” he said.

Many of the postinjury comorbidities emerged a median of 3.5 years after TBI, regardless of severity. But some of the cardiovascular and psychiatric conditions emerged far sooner than that.

That’s important because research suggests less than half of patients with TBI receive follow-up care.

“It does make sense for folks who are interacting with people who’ve had a TBI to be suspicious of medical comorbidities relatively early on, within the first couple of years,” Dr. Zafonte said.

In an invited commentary, Vijay Krishnamoorthy, MD, MPH, PhD, Duke University, Durham, N.C., and Monica S. Vavilala, MD, University of Washington, Seattle, highlight some of the study’s limitations, including a lack of information on comorbidity severity and the lack of a matched group of patients who experienced non-head trauma.

Despite those limitations, the study offers important information on how TBI may affect organs beyond the brain, they noted.

“These observations, if replicated in future studies, raise intriguing implications in the future care of patients with TBI, including heightened chronic disease-screening measures and possibly enhanced guidelines for chronic extracranial organ system care for patients who experience TBI,” Dr. Krishnamoorthy and Dr. Vavilala wrote.

The study received no specific funding. Dr. Zafonte reported having received personal fees from Springer/Demos, serving on scientific advisory boards for Myomo and OnCare and has received funding from the Football Players Health Study at Harvard, funded in part by the National Football League Players Association. Dr. Krishnamoorthy and Dr. Vavilala disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Women with systemic lupus erythematosus (SLE) experience worse outcomes after an acute stroke than does the general population, but men with SLE do not, according to an analysis of the U.S. National Inpatient Sample presented at the annual meeting of the British Society for Rheumatology.

In a study of more than 1.5 million cases of acute stroke recorded in the United States between 2015 and 2018, women with SLE were more likely to be hospitalized for longer and less likely to be routinely discharged into their home environment than were those without SLE. No such association was found for men with SLE.

“The findings imply that primary stroke prevention is of utmost importance, especially in females with SLE,” said Sona Jesenakova, a fourth-year medical student at the University of Aberdeen (Scotland).

“There might be a need to explore more effective and targeted treatment strategies to try and minimize these excessive adverse acute stroke outcomes, especially in females with SLE suffering from stroke,” she suggested.

“Even though males form only a minority of the SLE patient population, some studies have shown that they are prone to suffer from worse disease outcomes,” Ms. Jesenakova said.

Importantly, “male sex has been identified as a risk factor for death early in the course of SLE,” she added, highlighting that sex differences do seem to exist in SLE.

Stroke is an important outcome to look at because people with SLE are known to be at higher risk for developing atherosclerosis, which is a widely known risk factor for ischemic stroke, and with antiphospholipid antibody positivity and uncontrolled disease activity, that risk can be increased. A meta-analysis of older studies has suggested that the risk for death after a stroke is 68% higher in people with SLE than in those without.

To examine the risk for death and other in-hospital outcomes in a more contemporary population, Ms. Jesenakova and associates used data from the National Inpatient Sample, a large, publicly available database that contains inpatient health care information from across the United States. Their sample population consisted of 1,581,430 individuals who had been hospitalized for stroke. Of these, there were 6,100 women and 940 men who had SLE; the remainder served as the ‘no-SLE’ control population.

As might be expected, patients with SLE were about 10 years younger than those without SLE; the median age of women and men with SLE and those without SLE were a respective 60, 61, and 71 years.

There was no difference in the type of stroke between the SLE and no-SLE groups; most had an ischemic stroke (around 89%) rather than a hemorrhagic stroke (around 11%).

The researchers analyzed three key outcomes: mortality at discharge, hospitalization prolonged to a stay of more than 4 days, and routine home discharge, meaning that the patient was able to be discharged home versus more specialist facilities such as a nursing home.

They conducted a multivariate analysis with adjustments made for potential confounding factors such as age, ethnicity, type of stroke, and revascularization treatment. Comorbidities, including major cardiovascular disease, were also accounted for.

Although women with SLE were 21% more likely to die than patients without SLE, men with SLE were 24% less likely to die than was the no-SLE population. However, these differences were not statistically significant.

Women with SLE were 20% more likely to have a prolonged hospital stay and 28% less likely to have a routine home discharge, compared with patients who did not have SLE. The 95% confidence intervals were statistically significant, which was not seen when comparing the same outcomes in men with SLE (odds ratios of 1.06 and 1.18, respectively).

“As for males, even though we didn’t find anything of statistical significance, we have to bear in mind that the sample we had was quite small, and thus these results need to be interpreted with caution,” Ms. Jesenakova said. “We also think that we identified a gap in the current knowledge, and as such, further research is needed to help us understand the influence of male sex on acute stroke outcomes in patients with comorbid SLE.”

The researchers performed a secondary analysis looking at the use of revascularization treatments for ischemic stroke and found that there were no differences between individuals with and without SLE. This analysis considered the use of intravenous thrombolysis and endovascular thrombectomy in just over 1.4 million cases but did not look at sex-specific differences.

Ms. Jesenakova had no conflicts of interest to disclose.

Women with systemic lupus erythematosus (SLE) experience worse outcomes after an acute stroke than does the general population, but men with SLE do not, according to an analysis of the U.S. National Inpatient Sample presented at the annual meeting of the British Society for Rheumatology.

In a study of more than 1.5 million cases of acute stroke recorded in the United States between 2015 and 2018, women with SLE were more likely to be hospitalized for longer and less likely to be routinely discharged into their home environment than were those without SLE. No such association was found for men with SLE.

“The findings imply that primary stroke prevention is of utmost importance, especially in females with SLE,” said Sona Jesenakova, a fourth-year medical student at the University of Aberdeen (Scotland).

“There might be a need to explore more effective and targeted treatment strategies to try and minimize these excessive adverse acute stroke outcomes, especially in females with SLE suffering from stroke,” she suggested.

“Even though males form only a minority of the SLE patient population, some studies have shown that they are prone to suffer from worse disease outcomes,” Ms. Jesenakova said.

Importantly, “male sex has been identified as a risk factor for death early in the course of SLE,” she added, highlighting that sex differences do seem to exist in SLE.

Stroke is an important outcome to look at because people with SLE are known to be at higher risk for developing atherosclerosis, which is a widely known risk factor for ischemic stroke, and with antiphospholipid antibody positivity and uncontrolled disease activity, that risk can be increased. A meta-analysis of older studies has suggested that the risk for death after a stroke is 68% higher in people with SLE than in those without.

To examine the risk for death and other in-hospital outcomes in a more contemporary population, Ms. Jesenakova and associates used data from the National Inpatient Sample, a large, publicly available database that contains inpatient health care information from across the United States. Their sample population consisted of 1,581,430 individuals who had been hospitalized for stroke. Of these, there were 6,100 women and 940 men who had SLE; the remainder served as the ‘no-SLE’ control population.

As might be expected, patients with SLE were about 10 years younger than those without SLE; the median age of women and men with SLE and those without SLE were a respective 60, 61, and 71 years.

There was no difference in the type of stroke between the SLE and no-SLE groups; most had an ischemic stroke (around 89%) rather than a hemorrhagic stroke (around 11%).

The researchers analyzed three key outcomes: mortality at discharge, hospitalization prolonged to a stay of more than 4 days, and routine home discharge, meaning that the patient was able to be discharged home versus more specialist facilities such as a nursing home.

They conducted a multivariate analysis with adjustments made for potential confounding factors such as age, ethnicity, type of stroke, and revascularization treatment. Comorbidities, including major cardiovascular disease, were also accounted for.

Although women with SLE were 21% more likely to die than patients without SLE, men with SLE were 24% less likely to die than was the no-SLE population. However, these differences were not statistically significant.

Women with SLE were 20% more likely to have a prolonged hospital stay and 28% less likely to have a routine home discharge, compared with patients who did not have SLE. The 95% confidence intervals were statistically significant, which was not seen when comparing the same outcomes in men with SLE (odds ratios of 1.06 and 1.18, respectively).

“As for males, even though we didn’t find anything of statistical significance, we have to bear in mind that the sample we had was quite small, and thus these results need to be interpreted with caution,” Ms. Jesenakova said. “We also think that we identified a gap in the current knowledge, and as such, further research is needed to help us understand the influence of male sex on acute stroke outcomes in patients with comorbid SLE.”

The researchers performed a secondary analysis looking at the use of revascularization treatments for ischemic stroke and found that there were no differences between individuals with and without SLE. This analysis considered the use of intravenous thrombolysis and endovascular thrombectomy in just over 1.4 million cases but did not look at sex-specific differences.

Ms. Jesenakova had no conflicts of interest to disclose.

Women with systemic lupus erythematosus (SLE) experience worse outcomes after an acute stroke than does the general population, but men with SLE do not, according to an analysis of the U.S. National Inpatient Sample presented at the annual meeting of the British Society for Rheumatology.

In a study of more than 1.5 million cases of acute stroke recorded in the United States between 2015 and 2018, women with SLE were more likely to be hospitalized for longer and less likely to be routinely discharged into their home environment than were those without SLE. No such association was found for men with SLE.

“The findings imply that primary stroke prevention is of utmost importance, especially in females with SLE,” said Sona Jesenakova, a fourth-year medical student at the University of Aberdeen (Scotland).

“There might be a need to explore more effective and targeted treatment strategies to try and minimize these excessive adverse acute stroke outcomes, especially in females with SLE suffering from stroke,” she suggested.

“Even though males form only a minority of the SLE patient population, some studies have shown that they are prone to suffer from worse disease outcomes,” Ms. Jesenakova said.

Importantly, “male sex has been identified as a risk factor for death early in the course of SLE,” she added, highlighting that sex differences do seem to exist in SLE.

Stroke is an important outcome to look at because people with SLE are known to be at higher risk for developing atherosclerosis, which is a widely known risk factor for ischemic stroke, and with antiphospholipid antibody positivity and uncontrolled disease activity, that risk can be increased. A meta-analysis of older studies has suggested that the risk for death after a stroke is 68% higher in people with SLE than in those without.

To examine the risk for death and other in-hospital outcomes in a more contemporary population, Ms. Jesenakova and associates used data from the National Inpatient Sample, a large, publicly available database that contains inpatient health care information from across the United States. Their sample population consisted of 1,581,430 individuals who had been hospitalized for stroke. Of these, there were 6,100 women and 940 men who had SLE; the remainder served as the ‘no-SLE’ control population.

As might be expected, patients with SLE were about 10 years younger than those without SLE; the median age of women and men with SLE and those without SLE were a respective 60, 61, and 71 years.

There was no difference in the type of stroke between the SLE and no-SLE groups; most had an ischemic stroke (around 89%) rather than a hemorrhagic stroke (around 11%).

The researchers analyzed three key outcomes: mortality at discharge, hospitalization prolonged to a stay of more than 4 days, and routine home discharge, meaning that the patient was able to be discharged home versus more specialist facilities such as a nursing home.

They conducted a multivariate analysis with adjustments made for potential confounding factors such as age, ethnicity, type of stroke, and revascularization treatment. Comorbidities, including major cardiovascular disease, were also accounted for.

Although women with SLE were 21% more likely to die than patients without SLE, men with SLE were 24% less likely to die than was the no-SLE population. However, these differences were not statistically significant.

Women with SLE were 20% more likely to have a prolonged hospital stay and 28% less likely to have a routine home discharge, compared with patients who did not have SLE. The 95% confidence intervals were statistically significant, which was not seen when comparing the same outcomes in men with SLE (odds ratios of 1.06 and 1.18, respectively).

“As for males, even though we didn’t find anything of statistical significance, we have to bear in mind that the sample we had was quite small, and thus these results need to be interpreted with caution,” Ms. Jesenakova said. “We also think that we identified a gap in the current knowledge, and as such, further research is needed to help us understand the influence of male sex on acute stroke outcomes in patients with comorbid SLE.”

The researchers performed a secondary analysis looking at the use of revascularization treatments for ischemic stroke and found that there were no differences between individuals with and without SLE. This analysis considered the use of intravenous thrombolysis and endovascular thrombectomy in just over 1.4 million cases but did not look at sex-specific differences.

Ms. Jesenakova had no conflicts of interest to disclose.

In the placebo-controlled REDUCE-IT trial, icosapent ethyl (IPE) was linked to a significant reduction in major adverse cardiovascular events (MACE) when administered on top of LDL cholesterol control, but a new substudy suggests a greater relative advantage in those with a prior myocardial infarction.

In the study as a whole, IPE (Vascepa, Amarin) was tied to a 20% reduction in CV death (hazard ratio, 0.80; P = .03), but it climbed to a 30% reduction (HR, 0.70; P = .01) in the subgroup with a prior MI, reported a multinational team of investigators led by Prakriti Gaba, MD, a cardiologist at Brigham and Women’s Hospital, Boston.

On the basis of these data, “the imperative to treat patients who have a history of prior MI is even stronger,” said Deepak L. Bhatt, MD, executive director of interventional cardiovascular programs at Brigham and Women’s Hospital.

The principal investigator of REDUCE-IT and a coauthor of this subanalysis, Dr. Bhatt said in an interview, “The significant reduction in cardiovascular mortality, as well as sudden cardiac death and cardiac arrest, really should make physicians strongly consider this therapy in eligible patients.”

The main results of the REDUCE-IT trial were published more than 3 years ago. It enrolled patients with established CV disease or diabetes with additional risk factors who were on a statin and had elevated triglyceride (TG) levels.

A 25% reduction in MACE reported

In those randomized to IPE, there was about a 25% reduction in the primary composite MACE outcome of cardiovascular death, nonfatal MI, nonfatal stroke, revascularization, and unstable angina relative to placebo. About the same relative reduction was achieved in the key secondary endpoint of CV death, nonfatal MI, and nonfatal stroke.

Some guidelines have been changed on the basis of these data. The National Lipid Association, for example, conferred a class 1 recommendation for adding IPE to other appropriate lipid-reducing therapies in any individual 45 years of age or older with atherosclerotic cardiovascular disease.

This new substudy (J Am Coll Cardiol. 2022 Apr 25; doi: 10.1016/j.jacc.2022.02.035), is likely to be influential for those guidelines not yet revised. In the substudy of the prior MI patients, the relative benefit of IPE for the primary and secondary MACE endpoints were of similar magnitude to the overall study population, but events occurred more frequently in the prior-MI subgroup, greatly increasing the statistical power of the advantage.


 

More MACE in prior MI patients

For example, the primary outcome was observed in 22% of the placebo patients in the overall REDUCE-IT analysis but in 26.1% of those with prior MI, so even though the relative risk reduction remained at about 25%, the statistical strength was a hundred-fold greater (P = .00001 vs. P < .001).

For the key secondary composite MACE endpoint, the relative reduction for those with a prior MI was modestly greater than the study as a whole (HR 0.71 vs. HR. 075) but the statistical strength was again magnified in those with a prior MI (P = .00006 vs. P < .001). In those with a prior MI , the advantage of receiving IPE was similar whether or not there had been a prior revascularization.

The 20% lower rate of all-cause mortality among prior MI patients receiving IPE rather than placebo fell just short of statistical significance (HR, 0.80; P = .054). Ischemic events on IPE were reduced by 35% (P = .0000001) and recurrent MI was reduced by 34% (P = .00009).

In the substudy as well as in the REDUCE-IT trial overall, IPE was well tolerated. A slightly higher rate of atrial fibrillation was reported in both.

The REDUCE-IT substudy evaluated 3,693 patients with a history of MI, representing 45% of the 8,179 patients randomized.

IPE, an ethyl ester of the omega-3 polyunsaturated fatty acid, initially attracted attention for its ability to reduce elevated TG. It was hoped this would address reduce residual risk in patients on maximally reduced LDL cholesterol. However, it is suspected that IPE exerts benefits additive to or independent of TG lowering, according to the authors of the REDUCE-IT substudy. These include attenuation of the inflammatory response, release of nitric oxide, and effects that support stabilization of atherosclerotic plaque.

The investigators reported that the pattern of response supports this theory. In the newly reported substudy, the primary event curves that included nonthrombotic events separated at about 1 year, but even curves for CV death and sudden cardiac death were more delayed.

This delay might be explained “by the slow but steady reduction in plaque volume, mitigation of inflammation, improvements in endothelial function, and membrane stabilization,” according to the authors, who cited studies suggesting each of these effects might not be wholly dependent on TG reductions alone.
 

Prior TG-lowering studies disappointing

In fact, several studies evaluating other strategies for TG reductions have been disappointing, according to an accompanying editorial (J Am Coll Cardiol. 2022 Apr 25; doi: 10.1016/j.jacc.2022.03.001). For example, the STRENGTH trial did not show clinical benefits despite a slightly greater reduction in TGs than that shown in REDUCE-IT (19% reduction vs. 18.3%).

Overall, the REDUCE-IT trial and the prior-MI REDUCE-IT substudy show that there is targetable residual risk in high risk patients on statin therapy. One of the authors of the editorial that accompanied the prior-MI substudy of REDUCE-IT, William E. Boden, MD, professor of medicine, Boston University, emphasized this point. On the basis of REDUCE-IT, he said he believes that IPE should be considered to have broad indications as an adjunctive treatment to other lipid-lowering strategies.

“My practice centers on optimizing secondary prevention in high-risk patients who have elevated TG levels despite well-controlled LDL levels on statins, ezetimibe, or even PCSK-9 [proprotein convertase subtilisin/kexin type 9] inhibitors,” Dr. Boden said in an interview. Patients with diabetes are notorious for presenting with this profile of dyslipidemia, but he added that “even nondiabetics with prior MI, acute coronary syndrome, or revascularization will benefit from the addition of IPE to high-potency statins.”

Although the American Heart Association and the American College of Cardiology have not yet updated their guidelines to include IPE, Dr. Boden pointed out that the European Society of Cardiology, the Canadian Cardiovascular Society, and the American Diabetes Society have.

Dr. Bhatt added that there is a clear message from REDUCE-IT that IPE addresses residual risk.

Targeting the subgroup of high-risk patients with elevated TGs “is easy” because they are so readily identifiable, according to Dr. Bhatt, but he said it should be used for any patient that meet the entry criteria used for REDUCE-IT.

“The overall results of REDUCE-IT were robustly positive, so I wouldn’t just use it in patients with prior MI,” Dr. Bhatt said.

Dr. Bhatt reports financial relationships with more than 20 pharmaceutical companies, including Amarin, which provided funding for this trial. Dr. Boden reports no potential conflicts of interest.

In the placebo-controlled REDUCE-IT trial, icosapent ethyl (IPE) was linked to a significant reduction in major adverse cardiovascular events (MACE) when administered on top of LDL cholesterol control, but a new substudy suggests a greater relative advantage in those with a prior myocardial infarction.

In the study as a whole, IPE (Vascepa, Amarin) was tied to a 20% reduction in CV death (hazard ratio, 0.80; P = .03), but it climbed to a 30% reduction (HR, 0.70; P = .01) in the subgroup with a prior MI, reported a multinational team of investigators led by Prakriti Gaba, MD, a cardiologist at Brigham and Women’s Hospital, Boston.

On the basis of these data, “the imperative to treat patients who have a history of prior MI is even stronger,” said Deepak L. Bhatt, MD, executive director of interventional cardiovascular programs at Brigham and Women’s Hospital.

The principal investigator of REDUCE-IT and a coauthor of this subanalysis, Dr. Bhatt said in an interview, “The significant reduction in cardiovascular mortality, as well as sudden cardiac death and cardiac arrest, really should make physicians strongly consider this therapy in eligible patients.”

The main results of the REDUCE-IT trial were published more than 3 years ago. It enrolled patients with established CV disease or diabetes with additional risk factors who were on a statin and had elevated triglyceride (TG) levels.

A 25% reduction in MACE reported

In those randomized to IPE, there was about a 25% reduction in the primary composite MACE outcome of cardiovascular death, nonfatal MI, nonfatal stroke, revascularization, and unstable angina relative to placebo. About the same relative reduction was achieved in the key secondary endpoint of CV death, nonfatal MI, and nonfatal stroke.

Some guidelines have been changed on the basis of these data. The National Lipid Association, for example, conferred a class 1 recommendation for adding IPE to other appropriate lipid-reducing therapies in any individual 45 years of age or older with atherosclerotic cardiovascular disease.

This new substudy (J Am Coll Cardiol. 2022 Apr 25; doi: 10.1016/j.jacc.2022.02.035), is likely to be influential for those guidelines not yet revised. In the substudy of the prior MI patients, the relative benefit of IPE for the primary and secondary MACE endpoints were of similar magnitude to the overall study population, but events occurred more frequently in the prior-MI subgroup, greatly increasing the statistical power of the advantage.


 

More MACE in prior MI patients

For example, the primary outcome was observed in 22% of the placebo patients in the overall REDUCE-IT analysis but in 26.1% of those with prior MI, so even though the relative risk reduction remained at about 25%, the statistical strength was a hundred-fold greater (P = .00001 vs. P < .001).

For the key secondary composite MACE endpoint, the relative reduction for those with a prior MI was modestly greater than the study as a whole (HR 0.71 vs. HR. 075) but the statistical strength was again magnified in those with a prior MI (P = .00006 vs. P < .001). In those with a prior MI , the advantage of receiving IPE was similar whether or not there had been a prior revascularization.

The 20% lower rate of all-cause mortality among prior MI patients receiving IPE rather than placebo fell just short of statistical significance (HR, 0.80; P = .054). Ischemic events on IPE were reduced by 35% (P = .0000001) and recurrent MI was reduced by 34% (P = .00009).

In the substudy as well as in the REDUCE-IT trial overall, IPE was well tolerated. A slightly higher rate of atrial fibrillation was reported in both.

The REDUCE-IT substudy evaluated 3,693 patients with a history of MI, representing 45% of the 8,179 patients randomized.

IPE, an ethyl ester of the omega-3 polyunsaturated fatty acid, initially attracted attention for its ability to reduce elevated TG. It was hoped this would address reduce residual risk in patients on maximally reduced LDL cholesterol. However, it is suspected that IPE exerts benefits additive to or independent of TG lowering, according to the authors of the REDUCE-IT substudy. These include attenuation of the inflammatory response, release of nitric oxide, and effects that support stabilization of atherosclerotic plaque.

The investigators reported that the pattern of response supports this theory. In the newly reported substudy, the primary event curves that included nonthrombotic events separated at about 1 year, but even curves for CV death and sudden cardiac death were more delayed.

This delay might be explained “by the slow but steady reduction in plaque volume, mitigation of inflammation, improvements in endothelial function, and membrane stabilization,” according to the authors, who cited studies suggesting each of these effects might not be wholly dependent on TG reductions alone.
 

Prior TG-lowering studies disappointing

In fact, several studies evaluating other strategies for TG reductions have been disappointing, according to an accompanying editorial (J Am Coll Cardiol. 2022 Apr 25; doi: 10.1016/j.jacc.2022.03.001). For example, the STRENGTH trial did not show clinical benefits despite a slightly greater reduction in TGs than that shown in REDUCE-IT (19% reduction vs. 18.3%).

Overall, the REDUCE-IT trial and the prior-MI REDUCE-IT substudy show that there is targetable residual risk in high risk patients on statin therapy. One of the authors of the editorial that accompanied the prior-MI substudy of REDUCE-IT, William E. Boden, MD, professor of medicine, Boston University, emphasized this point. On the basis of REDUCE-IT, he said he believes that IPE should be considered to have broad indications as an adjunctive treatment to other lipid-lowering strategies.

“My practice centers on optimizing secondary prevention in high-risk patients who have elevated TG levels despite well-controlled LDL levels on statins, ezetimibe, or even PCSK-9 [proprotein convertase subtilisin/kexin type 9] inhibitors,” Dr. Boden said in an interview. Patients with diabetes are notorious for presenting with this profile of dyslipidemia, but he added that “even nondiabetics with prior MI, acute coronary syndrome, or revascularization will benefit from the addition of IPE to high-potency statins.”

Although the American Heart Association and the American College of Cardiology have not yet updated their guidelines to include IPE, Dr. Boden pointed out that the European Society of Cardiology, the Canadian Cardiovascular Society, and the American Diabetes Society have.

Dr. Bhatt added that there is a clear message from REDUCE-IT that IPE addresses residual risk.

Targeting the subgroup of high-risk patients with elevated TGs “is easy” because they are so readily identifiable, according to Dr. Bhatt, but he said it should be used for any patient that meet the entry criteria used for REDUCE-IT.

“The overall results of REDUCE-IT were robustly positive, so I wouldn’t just use it in patients with prior MI,” Dr. Bhatt said.

Dr. Bhatt reports financial relationships with more than 20 pharmaceutical companies, including Amarin, which provided funding for this trial. Dr. Boden reports no potential conflicts of interest.

In the placebo-controlled REDUCE-IT trial, icosapent ethyl (IPE) was linked to a significant reduction in major adverse cardiovascular events (MACE) when administered on top of LDL cholesterol control, but a new substudy suggests a greater relative advantage in those with a prior myocardial infarction.

In the study as a whole, IPE (Vascepa, Amarin) was tied to a 20% reduction in CV death (hazard ratio, 0.80; P = .03), but it climbed to a 30% reduction (HR, 0.70; P = .01) in the subgroup with a prior MI, reported a multinational team of investigators led by Prakriti Gaba, MD, a cardiologist at Brigham and Women’s Hospital, Boston.

On the basis of these data, “the imperative to treat patients who have a history of prior MI is even stronger,” said Deepak L. Bhatt, MD, executive director of interventional cardiovascular programs at Brigham and Women’s Hospital.

The principal investigator of REDUCE-IT and a coauthor of this subanalysis, Dr. Bhatt said in an interview, “The significant reduction in cardiovascular mortality, as well as sudden cardiac death and cardiac arrest, really should make physicians strongly consider this therapy in eligible patients.”

The main results of the REDUCE-IT trial were published more than 3 years ago. It enrolled patients with established CV disease or diabetes with additional risk factors who were on a statin and had elevated triglyceride (TG) levels.

A 25% reduction in MACE reported

In those randomized to IPE, there was about a 25% reduction in the primary composite MACE outcome of cardiovascular death, nonfatal MI, nonfatal stroke, revascularization, and unstable angina relative to placebo. About the same relative reduction was achieved in the key secondary endpoint of CV death, nonfatal MI, and nonfatal stroke.

Some guidelines have been changed on the basis of these data. The National Lipid Association, for example, conferred a class 1 recommendation for adding IPE to other appropriate lipid-reducing therapies in any individual 45 years of age or older with atherosclerotic cardiovascular disease.

This new substudy (J Am Coll Cardiol. 2022 Apr 25; doi: 10.1016/j.jacc.2022.02.035), is likely to be influential for those guidelines not yet revised. In the substudy of the prior MI patients, the relative benefit of IPE for the primary and secondary MACE endpoints were of similar magnitude to the overall study population, but events occurred more frequently in the prior-MI subgroup, greatly increasing the statistical power of the advantage.


 

More MACE in prior MI patients

For example, the primary outcome was observed in 22% of the placebo patients in the overall REDUCE-IT analysis but in 26.1% of those with prior MI, so even though the relative risk reduction remained at about 25%, the statistical strength was a hundred-fold greater (P = .00001 vs. P < .001).

For the key secondary composite MACE endpoint, the relative reduction for those with a prior MI was modestly greater than the study as a whole (HR 0.71 vs. HR. 075) but the statistical strength was again magnified in those with a prior MI (P = .00006 vs. P < .001). In those with a prior MI , the advantage of receiving IPE was similar whether or not there had been a prior revascularization.

The 20% lower rate of all-cause mortality among prior MI patients receiving IPE rather than placebo fell just short of statistical significance (HR, 0.80; P = .054). Ischemic events on IPE were reduced by 35% (P = .0000001) and recurrent MI was reduced by 34% (P = .00009).

In the substudy as well as in the REDUCE-IT trial overall, IPE was well tolerated. A slightly higher rate of atrial fibrillation was reported in both.

The REDUCE-IT substudy evaluated 3,693 patients with a history of MI, representing 45% of the 8,179 patients randomized.

IPE, an ethyl ester of the omega-3 polyunsaturated fatty acid, initially attracted attention for its ability to reduce elevated TG. It was hoped this would address reduce residual risk in patients on maximally reduced LDL cholesterol. However, it is suspected that IPE exerts benefits additive to or independent of TG lowering, according to the authors of the REDUCE-IT substudy. These include attenuation of the inflammatory response, release of nitric oxide, and effects that support stabilization of atherosclerotic plaque.

The investigators reported that the pattern of response supports this theory. In the newly reported substudy, the primary event curves that included nonthrombotic events separated at about 1 year, but even curves for CV death and sudden cardiac death were more delayed.

This delay might be explained “by the slow but steady reduction in plaque volume, mitigation of inflammation, improvements in endothelial function, and membrane stabilization,” according to the authors, who cited studies suggesting each of these effects might not be wholly dependent on TG reductions alone.
 

Prior TG-lowering studies disappointing

In fact, several studies evaluating other strategies for TG reductions have been disappointing, according to an accompanying editorial (J Am Coll Cardiol. 2022 Apr 25; doi: 10.1016/j.jacc.2022.03.001). For example, the STRENGTH trial did not show clinical benefits despite a slightly greater reduction in TGs than that shown in REDUCE-IT (19% reduction vs. 18.3%).

Overall, the REDUCE-IT trial and the prior-MI REDUCE-IT substudy show that there is targetable residual risk in high risk patients on statin therapy. One of the authors of the editorial that accompanied the prior-MI substudy of REDUCE-IT, William E. Boden, MD, professor of medicine, Boston University, emphasized this point. On the basis of REDUCE-IT, he said he believes that IPE should be considered to have broad indications as an adjunctive treatment to other lipid-lowering strategies.

“My practice centers on optimizing secondary prevention in high-risk patients who have elevated TG levels despite well-controlled LDL levels on statins, ezetimibe, or even PCSK-9 [proprotein convertase subtilisin/kexin type 9] inhibitors,” Dr. Boden said in an interview. Patients with diabetes are notorious for presenting with this profile of dyslipidemia, but he added that “even nondiabetics with prior MI, acute coronary syndrome, or revascularization will benefit from the addition of IPE to high-potency statins.”

Although the American Heart Association and the American College of Cardiology have not yet updated their guidelines to include IPE, Dr. Boden pointed out that the European Society of Cardiology, the Canadian Cardiovascular Society, and the American Diabetes Society have.

Dr. Bhatt added that there is a clear message from REDUCE-IT that IPE addresses residual risk.

Targeting the subgroup of high-risk patients with elevated TGs “is easy” because they are so readily identifiable, according to Dr. Bhatt, but he said it should be used for any patient that meet the entry criteria used for REDUCE-IT.

“The overall results of REDUCE-IT were robustly positive, so I wouldn’t just use it in patients with prior MI,” Dr. Bhatt said.

Dr. Bhatt reports financial relationships with more than 20 pharmaceutical companies, including Amarin, which provided funding for this trial. Dr. Boden reports no potential conflicts of interest.