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Blood transfusions linked to intracerebral hemorrhage risk
In an exploratory analysis, patients receiving red blood cell transfusions from donors who later developed multiple spontaneous ICHs, and were assumed to have CAA, were at a significantly increased risk of developing spontaneous ICH themselves.
“This may suggest a transfusion-transmissible agent associated with some types of spontaneous ICH, although the findings may be susceptible to selection bias and residual confounding, and further research is needed to investigate if transfusion transmission of CAA might explain this association,” the investigators noted.
“We do not think that the findings motivate a change in practice, and we should not let these results discourage otherwise indicated blood transfusion,” said lead author Jingcheng Zhao, MD, PhD, with Karolinska University Hospital Solna, Stockholm.
The study was published online in the Journal of the American Medical Association.
Novel finding
Recent evidence suggests that CAA exhibits “prion-like” transmissivity, with reports of transmission through cadaveric pituitary hormone contaminated with amyloid-beta and tau protein, dura mater grafts, and possibly neurosurgical instruments.
CAA, which is characterized by the deposition of amyloid protein in the brain, is the second most common cause of spontaneous ICH.
The researchers hypothesized that transfusion transmission of CAA may manifest through an increased risk for spontaneous ICH among transfusion recipients given blood from a donor with spontaneous ICH. To explore this hypothesis, they analyzed national registry data from Sweden and Denmark for ICH in recipients of red blood cell transfusion from donors who themselves had ICH over the years after their blood donations, with the assumption that donors with two or more ICHs would likely have CAA.
The cohort included nearly 760,000 individuals in Sweden (median age, 65 years; 59% women) and 330,000 in Denmark (median age, 64 years; 58% women), with a median follow-up of 5.8 and 6.1 years, respectively.
Receiving red blood cell transfusions from donors who later developed multiple spontaneous ICHs was associated with a greater than twofold increased risk of developing spontaneous ICH, compared with receiving a transfusion from donors without subsequent ICH (hazard ratio, 2.73; P < .001 in the Swedish cohort and HR, 2.32; P = .04 in the Danish cohort).
“The observed increased risk of spontaneous ICH associated with receiving a red blood cell transfusion from a donor who later developed multiple spontaneous ICHs, corresponding to a 30-year cumulative incidence difference of 2.3%, is a novel finding,” the researchers wrote.
There was no increase in post-transfusion ICH risk among recipients whose donors had a single post–blood-donation ICH.
The findings were robust to several of the sensitivity analyses.
A “negative” control analysis of post-transfusion ischemic stroke (instead of ICH) found no increased risk among recipients of blood from donors who had single or multiple ICHs.
This study provides “exploratory evidence of possible transfusion-transmission of a factor that causes ICHs, but more research is needed to confirm and to understand the mechanism,” said Dr. Zhao.
The researchers noted that they did not directly assess CAA but expect it would be more common among donors who develop multiple spontaneous ICHs, “as CAA-related ICH has been reported to have a 7-fold increase for recurrent ICHs, compared with non–CAA-related ICH.”
Worrisome finding or false alarm?
In an accompanying editorial, Steven Greenberg, MD, PhD, with the department of neurology, Harvard Medical School, Boston, said there are “good reasons to treat the possibility of CAA transmission via blood transfusion seriously – and good reasons to remain skeptical, at least for the present.”
“Powerful” arguments in support of the findings include the robust study methodology and the “striking” similarity in results from the two registries, which argues against a chance finding. Another is the negative control with ischemic stroke as the outcome, which argues against unsuspected confounding-causing associations with all types of stroke, Dr. Greenberg noted.
Arguments for remaining “unconvinced” of the association center on the weakness of evidence for a plausible biological mechanism for the finding, he points out. Another is the short-time course of ICHs after blood transfusion, which is “quite challenging to explain,” Dr. Greenberg said. Nearly half of the ICHs among blood recipients occurred within 5 years of transfusion, which is “dramatically” faster than the 30- to 40-year interval reported between neurosurgical exposure to cadaveric tissue and first ICH, he added.
Another related “mechanistic reservation” is the plausibility that a transmissible species of amyloid-beta could travel from blood to brain in sufficient quantities to trigger advanced CAA or Alzheimer disease pathology, he wrote.
He added the current study leaves him “squarely at the corner of anxiety and skepticism.”
With more than 10 million units of blood transfused in the United States each year, even a modest increase in risk for future brain hemorrhages or dementia conferred by “an uncommon – but as of now undetectable – donor trait would represent a substantial public health concern,” Dr. Greenberg wrote.
“From the standpoint of scientific plausibility, however, even this well-conducted analysis is at risk of representing a false alarm,” he cautioned.
Looking ahead, Dr. Greenberg said one clear direction is independent replication, ideally with datasets in which donor and recipient dementia can be reliably ascertained to assess the possibility of Alzheimer’s disease as well as CAA transmissibility.
“The other challenge is for experimental biologists to consider the alternative possibility of transfusion-related acceleration of downstream steps in the CAA-ICH pathway, such as the vessel remodeling by which amyloid beta–laden vessels proceed to rupture and bleed.”
“The current study is not yet a reason for alarm, certainly not a reason to avoid otherwise indicated blood transfusion, but it is a strong call for more scientific digging,” Dr. Greenberg concluded.
The study was funded by grants from the Karolinska Institute, the Swedish Research Council, and Region Stockholm. Dr. Zhao and Dr. Greenberg report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In an exploratory analysis, patients receiving red blood cell transfusions from donors who later developed multiple spontaneous ICHs, and were assumed to have CAA, were at a significantly increased risk of developing spontaneous ICH themselves.
“This may suggest a transfusion-transmissible agent associated with some types of spontaneous ICH, although the findings may be susceptible to selection bias and residual confounding, and further research is needed to investigate if transfusion transmission of CAA might explain this association,” the investigators noted.
“We do not think that the findings motivate a change in practice, and we should not let these results discourage otherwise indicated blood transfusion,” said lead author Jingcheng Zhao, MD, PhD, with Karolinska University Hospital Solna, Stockholm.
The study was published online in the Journal of the American Medical Association.
Novel finding
Recent evidence suggests that CAA exhibits “prion-like” transmissivity, with reports of transmission through cadaveric pituitary hormone contaminated with amyloid-beta and tau protein, dura mater grafts, and possibly neurosurgical instruments.
CAA, which is characterized by the deposition of amyloid protein in the brain, is the second most common cause of spontaneous ICH.
The researchers hypothesized that transfusion transmission of CAA may manifest through an increased risk for spontaneous ICH among transfusion recipients given blood from a donor with spontaneous ICH. To explore this hypothesis, they analyzed national registry data from Sweden and Denmark for ICH in recipients of red blood cell transfusion from donors who themselves had ICH over the years after their blood donations, with the assumption that donors with two or more ICHs would likely have CAA.
The cohort included nearly 760,000 individuals in Sweden (median age, 65 years; 59% women) and 330,000 in Denmark (median age, 64 years; 58% women), with a median follow-up of 5.8 and 6.1 years, respectively.
Receiving red blood cell transfusions from donors who later developed multiple spontaneous ICHs was associated with a greater than twofold increased risk of developing spontaneous ICH, compared with receiving a transfusion from donors without subsequent ICH (hazard ratio, 2.73; P < .001 in the Swedish cohort and HR, 2.32; P = .04 in the Danish cohort).
“The observed increased risk of spontaneous ICH associated with receiving a red blood cell transfusion from a donor who later developed multiple spontaneous ICHs, corresponding to a 30-year cumulative incidence difference of 2.3%, is a novel finding,” the researchers wrote.
There was no increase in post-transfusion ICH risk among recipients whose donors had a single post–blood-donation ICH.
The findings were robust to several of the sensitivity analyses.
A “negative” control analysis of post-transfusion ischemic stroke (instead of ICH) found no increased risk among recipients of blood from donors who had single or multiple ICHs.
This study provides “exploratory evidence of possible transfusion-transmission of a factor that causes ICHs, but more research is needed to confirm and to understand the mechanism,” said Dr. Zhao.
The researchers noted that they did not directly assess CAA but expect it would be more common among donors who develop multiple spontaneous ICHs, “as CAA-related ICH has been reported to have a 7-fold increase for recurrent ICHs, compared with non–CAA-related ICH.”
Worrisome finding or false alarm?
In an accompanying editorial, Steven Greenberg, MD, PhD, with the department of neurology, Harvard Medical School, Boston, said there are “good reasons to treat the possibility of CAA transmission via blood transfusion seriously – and good reasons to remain skeptical, at least for the present.”
“Powerful” arguments in support of the findings include the robust study methodology and the “striking” similarity in results from the two registries, which argues against a chance finding. Another is the negative control with ischemic stroke as the outcome, which argues against unsuspected confounding-causing associations with all types of stroke, Dr. Greenberg noted.
Arguments for remaining “unconvinced” of the association center on the weakness of evidence for a plausible biological mechanism for the finding, he points out. Another is the short-time course of ICHs after blood transfusion, which is “quite challenging to explain,” Dr. Greenberg said. Nearly half of the ICHs among blood recipients occurred within 5 years of transfusion, which is “dramatically” faster than the 30- to 40-year interval reported between neurosurgical exposure to cadaveric tissue and first ICH, he added.
Another related “mechanistic reservation” is the plausibility that a transmissible species of amyloid-beta could travel from blood to brain in sufficient quantities to trigger advanced CAA or Alzheimer disease pathology, he wrote.
He added the current study leaves him “squarely at the corner of anxiety and skepticism.”
With more than 10 million units of blood transfused in the United States each year, even a modest increase in risk for future brain hemorrhages or dementia conferred by “an uncommon – but as of now undetectable – donor trait would represent a substantial public health concern,” Dr. Greenberg wrote.
“From the standpoint of scientific plausibility, however, even this well-conducted analysis is at risk of representing a false alarm,” he cautioned.
Looking ahead, Dr. Greenberg said one clear direction is independent replication, ideally with datasets in which donor and recipient dementia can be reliably ascertained to assess the possibility of Alzheimer’s disease as well as CAA transmissibility.
“The other challenge is for experimental biologists to consider the alternative possibility of transfusion-related acceleration of downstream steps in the CAA-ICH pathway, such as the vessel remodeling by which amyloid beta–laden vessels proceed to rupture and bleed.”
“The current study is not yet a reason for alarm, certainly not a reason to avoid otherwise indicated blood transfusion, but it is a strong call for more scientific digging,” Dr. Greenberg concluded.
The study was funded by grants from the Karolinska Institute, the Swedish Research Council, and Region Stockholm. Dr. Zhao and Dr. Greenberg report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In an exploratory analysis, patients receiving red blood cell transfusions from donors who later developed multiple spontaneous ICHs, and were assumed to have CAA, were at a significantly increased risk of developing spontaneous ICH themselves.
“This may suggest a transfusion-transmissible agent associated with some types of spontaneous ICH, although the findings may be susceptible to selection bias and residual confounding, and further research is needed to investigate if transfusion transmission of CAA might explain this association,” the investigators noted.
“We do not think that the findings motivate a change in practice, and we should not let these results discourage otherwise indicated blood transfusion,” said lead author Jingcheng Zhao, MD, PhD, with Karolinska University Hospital Solna, Stockholm.
The study was published online in the Journal of the American Medical Association.
Novel finding
Recent evidence suggests that CAA exhibits “prion-like” transmissivity, with reports of transmission through cadaveric pituitary hormone contaminated with amyloid-beta and tau protein, dura mater grafts, and possibly neurosurgical instruments.
CAA, which is characterized by the deposition of amyloid protein in the brain, is the second most common cause of spontaneous ICH.
The researchers hypothesized that transfusion transmission of CAA may manifest through an increased risk for spontaneous ICH among transfusion recipients given blood from a donor with spontaneous ICH. To explore this hypothesis, they analyzed national registry data from Sweden and Denmark for ICH in recipients of red blood cell transfusion from donors who themselves had ICH over the years after their blood donations, with the assumption that donors with two or more ICHs would likely have CAA.
The cohort included nearly 760,000 individuals in Sweden (median age, 65 years; 59% women) and 330,000 in Denmark (median age, 64 years; 58% women), with a median follow-up of 5.8 and 6.1 years, respectively.
Receiving red blood cell transfusions from donors who later developed multiple spontaneous ICHs was associated with a greater than twofold increased risk of developing spontaneous ICH, compared with receiving a transfusion from donors without subsequent ICH (hazard ratio, 2.73; P < .001 in the Swedish cohort and HR, 2.32; P = .04 in the Danish cohort).
“The observed increased risk of spontaneous ICH associated with receiving a red blood cell transfusion from a donor who later developed multiple spontaneous ICHs, corresponding to a 30-year cumulative incidence difference of 2.3%, is a novel finding,” the researchers wrote.
There was no increase in post-transfusion ICH risk among recipients whose donors had a single post–blood-donation ICH.
The findings were robust to several of the sensitivity analyses.
A “negative” control analysis of post-transfusion ischemic stroke (instead of ICH) found no increased risk among recipients of blood from donors who had single or multiple ICHs.
This study provides “exploratory evidence of possible transfusion-transmission of a factor that causes ICHs, but more research is needed to confirm and to understand the mechanism,” said Dr. Zhao.
The researchers noted that they did not directly assess CAA but expect it would be more common among donors who develop multiple spontaneous ICHs, “as CAA-related ICH has been reported to have a 7-fold increase for recurrent ICHs, compared with non–CAA-related ICH.”
Worrisome finding or false alarm?
In an accompanying editorial, Steven Greenberg, MD, PhD, with the department of neurology, Harvard Medical School, Boston, said there are “good reasons to treat the possibility of CAA transmission via blood transfusion seriously – and good reasons to remain skeptical, at least for the present.”
“Powerful” arguments in support of the findings include the robust study methodology and the “striking” similarity in results from the two registries, which argues against a chance finding. Another is the negative control with ischemic stroke as the outcome, which argues against unsuspected confounding-causing associations with all types of stroke, Dr. Greenberg noted.
Arguments for remaining “unconvinced” of the association center on the weakness of evidence for a plausible biological mechanism for the finding, he points out. Another is the short-time course of ICHs after blood transfusion, which is “quite challenging to explain,” Dr. Greenberg said. Nearly half of the ICHs among blood recipients occurred within 5 years of transfusion, which is “dramatically” faster than the 30- to 40-year interval reported between neurosurgical exposure to cadaveric tissue and first ICH, he added.
Another related “mechanistic reservation” is the plausibility that a transmissible species of amyloid-beta could travel from blood to brain in sufficient quantities to trigger advanced CAA or Alzheimer disease pathology, he wrote.
He added the current study leaves him “squarely at the corner of anxiety and skepticism.”
With more than 10 million units of blood transfused in the United States each year, even a modest increase in risk for future brain hemorrhages or dementia conferred by “an uncommon – but as of now undetectable – donor trait would represent a substantial public health concern,” Dr. Greenberg wrote.
“From the standpoint of scientific plausibility, however, even this well-conducted analysis is at risk of representing a false alarm,” he cautioned.
Looking ahead, Dr. Greenberg said one clear direction is independent replication, ideally with datasets in which donor and recipient dementia can be reliably ascertained to assess the possibility of Alzheimer’s disease as well as CAA transmissibility.
“The other challenge is for experimental biologists to consider the alternative possibility of transfusion-related acceleration of downstream steps in the CAA-ICH pathway, such as the vessel remodeling by which amyloid beta–laden vessels proceed to rupture and bleed.”
“The current study is not yet a reason for alarm, certainly not a reason to avoid otherwise indicated blood transfusion, but it is a strong call for more scientific digging,” Dr. Greenberg concluded.
The study was funded by grants from the Karolinska Institute, the Swedish Research Council, and Region Stockholm. Dr. Zhao and Dr. Greenberg report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
From JAMA
Low-dose steroids may not increase cardiovascular risk in rheumatoid arthritis
A daily prednisolone dose of 5 mg or higher is associated with increased risk for major adverse cardiovascular events (MACE) among patients with rheumatoid arthritis (RA), data suggest. Patients taking daily doses below this threshold did not appear to have an increased risk of MACE, compared with those not taking glucocorticoids (GCs).
Other studies of GCs and CV risk among RA patients have yielded conflicting results, especially for low-dose GCs. Findings from a 2020 study published in PLOS Medicine suggested that patients who had several immune-mediated inflammatory diseases – including RA – and who took less than a 5-mg prednisolone-equivalent dose daily had 74% higher risk for all-cause CVD, compared with nonusers. But results from a 2021 study published in Annals of the Rheumatic Diseases suggested that a daily prednisone dose of 4 mg or less did not increase cardiovascular events over a period of 6 months to 1 year.
These contradictory results were “primarily due to incomplete control of confounding variables, such as failure to adjust for C-reactive protein (CRP) levels,” Dr. Tam said. “Our study aimed to use a big data analytical approach to determine the effect of systemic GC dose and duration on the risk of major adverse cardiovascular events in patients with RA, while controlling for systemic inflammation, traditional CV risk factors, and other therapies.”
Is there a ‘safe’ dose for glucocorticoids?
To analyze this relationship, Dr. Lam and colleagues used the Hospital Authority Data Collaboration Laboratory, a citywide health care database. The investigators recruited patients with RA who had no history of MACE from 2006 to 2015 and followed them until the end of 2018. The primary outcome was the first occurrence of a MACE, defined as a composite of myocardial infarction (MI), unstable angina, ischemic or hemorrhagic cerebrovascular accident, transient ischemic attack, and CV death.
The study was published in Annals of the Rheumatic Diseases.
The analysis included 12,233 patients with RA and had over 105,826 person-years of follow-up. The average follow-up time was 8.7 years. During the study period, 860 patients had their first MACE. After controlling for confounding factors, a daily prednisolone dose of 5 mg or higher doubled the risk for MACE, compared with GC nonusers. MACE risk increased by 7% per month.
Long-term glucocorticoid use discouraged
Daily doses of less than 5 mg were not associated with higher MACE risk, but more research is necessary to understand whether these low doses are clinically efficacious, Dr. Tam said. “The study results suggest that a very-low-dose GC (less than 5 mg prednisolone daily) may be cardiovascular risk–neutral. However, further evaluation is needed to determine whether this dose is therapeutic. Other potential side effects, such as bone loss, increased infection risk, dyslipidemia, and hyperglycemia, should also be considered.”
Both the American College of Rheumatology and the European Alliance of Associations for Rheumatology acknowledge that short-term GCs may be necessary for some RA patients, but they emphasize using the smallest necessary dose for the shortest period possible because of the known toxicity of GCs.
“We recommend stopping GCs as soon as it is clinically feasible, in line with previous recommendations, until these issues are investigated further,” Dr. Tam added.
Dr. Bartels agreed that long-term use of GCs should be avoided if possible, even at lower doses, because although CV risk may be less of an issue, studies have shown an increased risk for infection even at GC doses of less than 5 mg a day.
How might risk increase with dose?
While the study showed a distinct difference in risk with doses of prednisolone higher and lower than 5 mg, more information on how risk increases with dose could be useful, said Beth Wallace, MD, an assistant professor in internal medicine at the University of Michigan, Ann Arbor, and a staff rheumatologist at the VA Ann Arbor Healthcare Center. She was also unaffiliated with the research. “If someone is on 5-10 mg ... how much better is that than being on 10-20 mg or being on 20-30 mg?” she asked. While these study findings are “very important,” she said, it would be useful to know the risk associated with 7.5 mg vs. a higher dose.
But even in this relatively healthy population in Hong Kong, “taking more than 5 mg of prednisolone doubles the risk of cardiovascular disease,” Dr. Wallace added. This is important for clinicians to know, especially if they are more cautious about prescribing steroids to older or sicker patients but are “using [the drugs] a little more indiscriminately in younger people and healthier people.”
The study did not receive outside funding. Dr. Tam and Dr. Bartels report no relevant financial relationships. Dr. Wallace has received a grant from the Department of Veterans Affairs Administration to study steroid tapering in RA.
A version of this article first appeared on Medscape.com.
A daily prednisolone dose of 5 mg or higher is associated with increased risk for major adverse cardiovascular events (MACE) among patients with rheumatoid arthritis (RA), data suggest. Patients taking daily doses below this threshold did not appear to have an increased risk of MACE, compared with those not taking glucocorticoids (GCs).
Other studies of GCs and CV risk among RA patients have yielded conflicting results, especially for low-dose GCs. Findings from a 2020 study published in PLOS Medicine suggested that patients who had several immune-mediated inflammatory diseases – including RA – and who took less than a 5-mg prednisolone-equivalent dose daily had 74% higher risk for all-cause CVD, compared with nonusers. But results from a 2021 study published in Annals of the Rheumatic Diseases suggested that a daily prednisone dose of 4 mg or less did not increase cardiovascular events over a period of 6 months to 1 year.
These contradictory results were “primarily due to incomplete control of confounding variables, such as failure to adjust for C-reactive protein (CRP) levels,” Dr. Tam said. “Our study aimed to use a big data analytical approach to determine the effect of systemic GC dose and duration on the risk of major adverse cardiovascular events in patients with RA, while controlling for systemic inflammation, traditional CV risk factors, and other therapies.”
Is there a ‘safe’ dose for glucocorticoids?
To analyze this relationship, Dr. Lam and colleagues used the Hospital Authority Data Collaboration Laboratory, a citywide health care database. The investigators recruited patients with RA who had no history of MACE from 2006 to 2015 and followed them until the end of 2018. The primary outcome was the first occurrence of a MACE, defined as a composite of myocardial infarction (MI), unstable angina, ischemic or hemorrhagic cerebrovascular accident, transient ischemic attack, and CV death.
The study was published in Annals of the Rheumatic Diseases.
The analysis included 12,233 patients with RA and had over 105,826 person-years of follow-up. The average follow-up time was 8.7 years. During the study period, 860 patients had their first MACE. After controlling for confounding factors, a daily prednisolone dose of 5 mg or higher doubled the risk for MACE, compared with GC nonusers. MACE risk increased by 7% per month.
Long-term glucocorticoid use discouraged
Daily doses of less than 5 mg were not associated with higher MACE risk, but more research is necessary to understand whether these low doses are clinically efficacious, Dr. Tam said. “The study results suggest that a very-low-dose GC (less than 5 mg prednisolone daily) may be cardiovascular risk–neutral. However, further evaluation is needed to determine whether this dose is therapeutic. Other potential side effects, such as bone loss, increased infection risk, dyslipidemia, and hyperglycemia, should also be considered.”
Both the American College of Rheumatology and the European Alliance of Associations for Rheumatology acknowledge that short-term GCs may be necessary for some RA patients, but they emphasize using the smallest necessary dose for the shortest period possible because of the known toxicity of GCs.
“We recommend stopping GCs as soon as it is clinically feasible, in line with previous recommendations, until these issues are investigated further,” Dr. Tam added.
Dr. Bartels agreed that long-term use of GCs should be avoided if possible, even at lower doses, because although CV risk may be less of an issue, studies have shown an increased risk for infection even at GC doses of less than 5 mg a day.
How might risk increase with dose?
While the study showed a distinct difference in risk with doses of prednisolone higher and lower than 5 mg, more information on how risk increases with dose could be useful, said Beth Wallace, MD, an assistant professor in internal medicine at the University of Michigan, Ann Arbor, and a staff rheumatologist at the VA Ann Arbor Healthcare Center. She was also unaffiliated with the research. “If someone is on 5-10 mg ... how much better is that than being on 10-20 mg or being on 20-30 mg?” she asked. While these study findings are “very important,” she said, it would be useful to know the risk associated with 7.5 mg vs. a higher dose.
But even in this relatively healthy population in Hong Kong, “taking more than 5 mg of prednisolone doubles the risk of cardiovascular disease,” Dr. Wallace added. This is important for clinicians to know, especially if they are more cautious about prescribing steroids to older or sicker patients but are “using [the drugs] a little more indiscriminately in younger people and healthier people.”
The study did not receive outside funding. Dr. Tam and Dr. Bartels report no relevant financial relationships. Dr. Wallace has received a grant from the Department of Veterans Affairs Administration to study steroid tapering in RA.
A version of this article first appeared on Medscape.com.
A daily prednisolone dose of 5 mg or higher is associated with increased risk for major adverse cardiovascular events (MACE) among patients with rheumatoid arthritis (RA), data suggest. Patients taking daily doses below this threshold did not appear to have an increased risk of MACE, compared with those not taking glucocorticoids (GCs).
Other studies of GCs and CV risk among RA patients have yielded conflicting results, especially for low-dose GCs. Findings from a 2020 study published in PLOS Medicine suggested that patients who had several immune-mediated inflammatory diseases – including RA – and who took less than a 5-mg prednisolone-equivalent dose daily had 74% higher risk for all-cause CVD, compared with nonusers. But results from a 2021 study published in Annals of the Rheumatic Diseases suggested that a daily prednisone dose of 4 mg or less did not increase cardiovascular events over a period of 6 months to 1 year.
These contradictory results were “primarily due to incomplete control of confounding variables, such as failure to adjust for C-reactive protein (CRP) levels,” Dr. Tam said. “Our study aimed to use a big data analytical approach to determine the effect of systemic GC dose and duration on the risk of major adverse cardiovascular events in patients with RA, while controlling for systemic inflammation, traditional CV risk factors, and other therapies.”
Is there a ‘safe’ dose for glucocorticoids?
To analyze this relationship, Dr. Lam and colleagues used the Hospital Authority Data Collaboration Laboratory, a citywide health care database. The investigators recruited patients with RA who had no history of MACE from 2006 to 2015 and followed them until the end of 2018. The primary outcome was the first occurrence of a MACE, defined as a composite of myocardial infarction (MI), unstable angina, ischemic or hemorrhagic cerebrovascular accident, transient ischemic attack, and CV death.
The study was published in Annals of the Rheumatic Diseases.
The analysis included 12,233 patients with RA and had over 105,826 person-years of follow-up. The average follow-up time was 8.7 years. During the study period, 860 patients had their first MACE. After controlling for confounding factors, a daily prednisolone dose of 5 mg or higher doubled the risk for MACE, compared with GC nonusers. MACE risk increased by 7% per month.
Long-term glucocorticoid use discouraged
Daily doses of less than 5 mg were not associated with higher MACE risk, but more research is necessary to understand whether these low doses are clinically efficacious, Dr. Tam said. “The study results suggest that a very-low-dose GC (less than 5 mg prednisolone daily) may be cardiovascular risk–neutral. However, further evaluation is needed to determine whether this dose is therapeutic. Other potential side effects, such as bone loss, increased infection risk, dyslipidemia, and hyperglycemia, should also be considered.”
Both the American College of Rheumatology and the European Alliance of Associations for Rheumatology acknowledge that short-term GCs may be necessary for some RA patients, but they emphasize using the smallest necessary dose for the shortest period possible because of the known toxicity of GCs.
“We recommend stopping GCs as soon as it is clinically feasible, in line with previous recommendations, until these issues are investigated further,” Dr. Tam added.
Dr. Bartels agreed that long-term use of GCs should be avoided if possible, even at lower doses, because although CV risk may be less of an issue, studies have shown an increased risk for infection even at GC doses of less than 5 mg a day.
How might risk increase with dose?
While the study showed a distinct difference in risk with doses of prednisolone higher and lower than 5 mg, more information on how risk increases with dose could be useful, said Beth Wallace, MD, an assistant professor in internal medicine at the University of Michigan, Ann Arbor, and a staff rheumatologist at the VA Ann Arbor Healthcare Center. She was also unaffiliated with the research. “If someone is on 5-10 mg ... how much better is that than being on 10-20 mg or being on 20-30 mg?” she asked. While these study findings are “very important,” she said, it would be useful to know the risk associated with 7.5 mg vs. a higher dose.
But even in this relatively healthy population in Hong Kong, “taking more than 5 mg of prednisolone doubles the risk of cardiovascular disease,” Dr. Wallace added. This is important for clinicians to know, especially if they are more cautious about prescribing steroids to older or sicker patients but are “using [the drugs] a little more indiscriminately in younger people and healthier people.”
The study did not receive outside funding. Dr. Tam and Dr. Bartels report no relevant financial relationships. Dr. Wallace has received a grant from the Department of Veterans Affairs Administration to study steroid tapering in RA.
A version of this article first appeared on Medscape.com.
FROM ANNALS OF THE RHEUMATIC DISEASES
Thrombectomy improves outcomes in pediatric stroke
A matched case-control study followed 52 patients in Canada and Australia with acute stroke and assessed functional outcomes at 3 months for those who received thrombectomy, compared with those who did not. Patients receiving the procedure had significantly improved clinical outcomes (odds ratio [OR], 3.76). The procedure is the standard of care for adults with large vessel occlusion (LVO) stroke, but limited data exist for children.
“In the absence of a randomized trial, this case-control study demonstrates better clinical outcomes with thrombectomy than medical management for pediatric patients aged 2 to 18 years with anterior circulation LVO stroke,” the authors concluded. The study was published in JAMA Neurology.
Improved results
Untreated LVO stroke is associated with poor outcomes, indicated in this study with scoring based on the modified Rankin Scale. Based on this scoring, 53.8% of patients who were managed conservatively had poor outcomes (moderate disability or greater) at 3 months, confirming previous findings. The data were drawn from five hospitals in Australia and Canada between January 2011 and April 2022.
Removing blood clots with mechanical thrombectomy resulted in improved outcomes 3 months after stroke for the patients included in the study, compared with the neuroprotective measures of medical therapy alone. The improved outcomes persisted in the final available follow-up (OR, 3.65).
In adults, thrombectomy has previously been demonstrated to be a safe and effective treatment for LVO stroke and is currently the standard of care. This study sought to expand the data for pediatric patients, for whom stroke is rarer and difficult to diagnose.
The authors cautioned, however, that the outcomes are from hospitals with pediatric neurology expertise and should not be generalized to settings without specialists.
Case-control study
While previous population-based studies of children with LVO stroke found that conservative treatment was associated with poor outcomes, these studies may include significant selection bias. The investigators chose to conduct the case-control study as an alternative to a randomized control trial, which would require withholding treatment from some patients and would not be considered ethical.
The study included 26 patients in each cohort, either receiving mechanical thrombectomy or medical treatment alone. The investigators matched patients by site and side of occlusion, age, and sex. Cases that could not be matched by site of occlusion, the primary criterion, were excluded.
With this methodology, the investigators reduced the impact of selection bias with the aim of providing “the next highest level of comparative evidence,” they stated in the study. However, they also noted that, without randomization, there is likely still some selection bias present.
The two cohorts were not significantly different based on factors such as sex or age. All patients in the study presented within 24 hours of symptom onset, with most eligible for thrombectomy by adult standards. There was a difference between the two cohorts in the timing of arrival to a dedicated hospital and imaging. “Our triage, imaging, and decision-making pathways require streamlining,” the authors concluded, regarding the difference.
‘A heterogeneous condition’
In a comment, Ratika Srivastava, MD, a pediatric neurologist at the University of Alberta, Edmonton, said she was glad to see a well-designed study dedicated to pediatric stroke. Neurologists have traditionally extrapolated from research on adult stroke due to the rarity of pediatric stroke and difficulty of diagnosis.
While physicians have previously relied on findings in adults, stroke presents differently in children. “The challenge is that it’s such a heterogeneous condition,” said Dr. Srivastava, who was not involved in the study. In children, stroke may have several different etiologies, such as a lesion in the heart or arterial disease. “Sometimes it’s amenable to taking the clot out and sometimes it’s not. So you have to figure out: Are they a good candidate for thrombectomy?” This study helps demonstrate that thrombectomy is a good option for some children with LVO stroke, she said.
The study was independently supported. Dr. Srivastava reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A matched case-control study followed 52 patients in Canada and Australia with acute stroke and assessed functional outcomes at 3 months for those who received thrombectomy, compared with those who did not. Patients receiving the procedure had significantly improved clinical outcomes (odds ratio [OR], 3.76). The procedure is the standard of care for adults with large vessel occlusion (LVO) stroke, but limited data exist for children.
“In the absence of a randomized trial, this case-control study demonstrates better clinical outcomes with thrombectomy than medical management for pediatric patients aged 2 to 18 years with anterior circulation LVO stroke,” the authors concluded. The study was published in JAMA Neurology.
Improved results
Untreated LVO stroke is associated with poor outcomes, indicated in this study with scoring based on the modified Rankin Scale. Based on this scoring, 53.8% of patients who were managed conservatively had poor outcomes (moderate disability or greater) at 3 months, confirming previous findings. The data were drawn from five hospitals in Australia and Canada between January 2011 and April 2022.
Removing blood clots with mechanical thrombectomy resulted in improved outcomes 3 months after stroke for the patients included in the study, compared with the neuroprotective measures of medical therapy alone. The improved outcomes persisted in the final available follow-up (OR, 3.65).
In adults, thrombectomy has previously been demonstrated to be a safe and effective treatment for LVO stroke and is currently the standard of care. This study sought to expand the data for pediatric patients, for whom stroke is rarer and difficult to diagnose.
The authors cautioned, however, that the outcomes are from hospitals with pediatric neurology expertise and should not be generalized to settings without specialists.
Case-control study
While previous population-based studies of children with LVO stroke found that conservative treatment was associated with poor outcomes, these studies may include significant selection bias. The investigators chose to conduct the case-control study as an alternative to a randomized control trial, which would require withholding treatment from some patients and would not be considered ethical.
The study included 26 patients in each cohort, either receiving mechanical thrombectomy or medical treatment alone. The investigators matched patients by site and side of occlusion, age, and sex. Cases that could not be matched by site of occlusion, the primary criterion, were excluded.
With this methodology, the investigators reduced the impact of selection bias with the aim of providing “the next highest level of comparative evidence,” they stated in the study. However, they also noted that, without randomization, there is likely still some selection bias present.
The two cohorts were not significantly different based on factors such as sex or age. All patients in the study presented within 24 hours of symptom onset, with most eligible for thrombectomy by adult standards. There was a difference between the two cohorts in the timing of arrival to a dedicated hospital and imaging. “Our triage, imaging, and decision-making pathways require streamlining,” the authors concluded, regarding the difference.
‘A heterogeneous condition’
In a comment, Ratika Srivastava, MD, a pediatric neurologist at the University of Alberta, Edmonton, said she was glad to see a well-designed study dedicated to pediatric stroke. Neurologists have traditionally extrapolated from research on adult stroke due to the rarity of pediatric stroke and difficulty of diagnosis.
While physicians have previously relied on findings in adults, stroke presents differently in children. “The challenge is that it’s such a heterogeneous condition,” said Dr. Srivastava, who was not involved in the study. In children, stroke may have several different etiologies, such as a lesion in the heart or arterial disease. “Sometimes it’s amenable to taking the clot out and sometimes it’s not. So you have to figure out: Are they a good candidate for thrombectomy?” This study helps demonstrate that thrombectomy is a good option for some children with LVO stroke, she said.
The study was independently supported. Dr. Srivastava reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A matched case-control study followed 52 patients in Canada and Australia with acute stroke and assessed functional outcomes at 3 months for those who received thrombectomy, compared with those who did not. Patients receiving the procedure had significantly improved clinical outcomes (odds ratio [OR], 3.76). The procedure is the standard of care for adults with large vessel occlusion (LVO) stroke, but limited data exist for children.
“In the absence of a randomized trial, this case-control study demonstrates better clinical outcomes with thrombectomy than medical management for pediatric patients aged 2 to 18 years with anterior circulation LVO stroke,” the authors concluded. The study was published in JAMA Neurology.
Improved results
Untreated LVO stroke is associated with poor outcomes, indicated in this study with scoring based on the modified Rankin Scale. Based on this scoring, 53.8% of patients who were managed conservatively had poor outcomes (moderate disability or greater) at 3 months, confirming previous findings. The data were drawn from five hospitals in Australia and Canada between January 2011 and April 2022.
Removing blood clots with mechanical thrombectomy resulted in improved outcomes 3 months after stroke for the patients included in the study, compared with the neuroprotective measures of medical therapy alone. The improved outcomes persisted in the final available follow-up (OR, 3.65).
In adults, thrombectomy has previously been demonstrated to be a safe and effective treatment for LVO stroke and is currently the standard of care. This study sought to expand the data for pediatric patients, for whom stroke is rarer and difficult to diagnose.
The authors cautioned, however, that the outcomes are from hospitals with pediatric neurology expertise and should not be generalized to settings without specialists.
Case-control study
While previous population-based studies of children with LVO stroke found that conservative treatment was associated with poor outcomes, these studies may include significant selection bias. The investigators chose to conduct the case-control study as an alternative to a randomized control trial, which would require withholding treatment from some patients and would not be considered ethical.
The study included 26 patients in each cohort, either receiving mechanical thrombectomy or medical treatment alone. The investigators matched patients by site and side of occlusion, age, and sex. Cases that could not be matched by site of occlusion, the primary criterion, were excluded.
With this methodology, the investigators reduced the impact of selection bias with the aim of providing “the next highest level of comparative evidence,” they stated in the study. However, they also noted that, without randomization, there is likely still some selection bias present.
The two cohorts were not significantly different based on factors such as sex or age. All patients in the study presented within 24 hours of symptom onset, with most eligible for thrombectomy by adult standards. There was a difference between the two cohorts in the timing of arrival to a dedicated hospital and imaging. “Our triage, imaging, and decision-making pathways require streamlining,” the authors concluded, regarding the difference.
‘A heterogeneous condition’
In a comment, Ratika Srivastava, MD, a pediatric neurologist at the University of Alberta, Edmonton, said she was glad to see a well-designed study dedicated to pediatric stroke. Neurologists have traditionally extrapolated from research on adult stroke due to the rarity of pediatric stroke and difficulty of diagnosis.
While physicians have previously relied on findings in adults, stroke presents differently in children. “The challenge is that it’s such a heterogeneous condition,” said Dr. Srivastava, who was not involved in the study. In children, stroke may have several different etiologies, such as a lesion in the heart or arterial disease. “Sometimes it’s amenable to taking the clot out and sometimes it’s not. So you have to figure out: Are they a good candidate for thrombectomy?” This study helps demonstrate that thrombectomy is a good option for some children with LVO stroke, she said.
The study was independently supported. Dr. Srivastava reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JAMA NEUROLOGY
LAAO tied to fewer post-fall bleeds than DOACs in AF
Left atrial appendage occlusion (LAAO) is associated with fewer injuries and less bleeding from falls than anticoagulant medications in patients with atrial fibrillation (AF) and a previous stroke, a new cohort study suggests.
Investigators prospectively followed more than 1,250 patients with AF and a previous ischemic stroke. Approximately half underwent LAAO, while the other half were treated with direct oral anticoagulants (DOACs). Patients were followed for close to 2 years.
Slightly more than 20% of patients fell during that period in each group, and , who were not taking anticoagulants. The risk for a major bleed, including an intracranial bleed, was 70% lower in the LAAO group.
LAAO has previously been considered for people at risk of bleeding events – for example, those with gastrointestinal (GI) bleeds, bruising, or intracranial bleeding – but had not yet been studied in those at risk for falls, coauthor Moussa Mansour, MD, professor of medicine, Harvard Medical School, and director of the Atrial Fibrillation Program at Massachusetts General Hospital, Boston, said in an interview.
This is the first study to focus on LAAO specifically for those at risk for falling and demonstrated that the LAAO has utility in this population as well, which is important because the U.S. population is an aging population, and at advanced ages, “people’s balance becomes unsteady and they are at high risk of falling,” he said.
The findings were published online as a research letter in the Journal of the American College of Cardiology.
Multidisciplinary collaboration
“More than one in five of our neurology patients with AF fall – many with devastating consequences – making stroke prevention extremely challenging,” senior author MingMing Ning, MD, MMsc, associate professor of neurology, Harvard Medical School, and director of the Cardio-Neurology and the Clinical Proteomics Research Center at Massachusetts General Hospital, Boston, said in an interview.
“There is a dire need to tailor treatment to keep our patients safe while preventing future strokes,” she said.
Anticoagulants are effective in stroke prevention in these patients but are associated with a higher risk for major bleeding, especially after a fall.
The current prospective observational study recruited 1,266 stroke patients who were treated either with LAAO or DOACs (n = 570 and 696, respectively). Patients were followed for a median of 1.8 years (IQR: 0.9-3.0).
During the follow-up period, 22.6% of LAAO-treated patients and 22.7% of DOAC-treated patients sustained a fall (mean age 78.9 years, 57.4% male and 79.1 years, 52.5% male respectively).
Fall severity, evaluated via the Injury Severity Score, was less in the LAAO vs. the DOAC group, with ISS scores of 1 (IQR 1-4) vs. 4 (IQR 1.75-9).
LAAO was associated with significantly reduced severity of fall-related injuries (OR, –1.09, 95% confidence interval [CI], –1.52 to –0.66; P < .001) – a finding that remained statistically significant after adjustment for confounders such as age, sex, and comorbidities contributing to fall risk, such as hypertension, hyperlipidemia, and diabetes.
The incidence of major trauma (defined as ISS >15) was lower in the LAAO group, compared to the DOAC group (0.8% vs. 6.3%, respectively, P = .026), and LAAO-treated patients had a shorter length of hospital stay, with fewer LAAO patients compared with DOAC patients staying in the hospital for more than 3 days (17% vs. 29.1%, respectively, P = .018).
The risk for major post-fall bleeding was lower in the LAAO vs. the DOAC group (4.7% vs. 15.2%, AOR, 0.29; 95% CI, 0.11-0.73; P = .009) – a finding that included intracranial bleeding (3.1% vs. 9.5%; AOR, 0.29; 95% CI, 0.09-0.90; P = .033).
“Many people are living to advanced ages, where their balance becomes unsteady, and in addition, we have an increase in the prevalence of AF because people are living longer and it’s a disease of the elderly, because we have more hypertension, and we also have more tools to diagnose AF. It’s almost a ‘perfect storm’ situation, and we need effective interventions in this population,” said Dr. Mansour.
Before the study, people at risk for falling were not being considered for LAAO; but now, “we believe they should be considered,” he added. “And although people in the current study had all experienced an ischemic stroke, any patient at risk of a fall will potentially benefit.”
Beyond demonstrating the role of LAAO in reducing the risk of post-fall bleeding injuries, the study – which was conducted by specialists in neurology and cardiology among other fields – highlights the importance of multidisciplinary collaboration, which is “key” for effective stroke prevention, Dr. Ning said.
She emphasized that “we need to learn from our patients and tailor treatment to their needs. A patient’s risk of falling, lifestyle, and medication adherence are all important for individualizing care and improving quality of life.”
Better option
Commenting for this article, Andrea Natale, MD, executive medical director, Texas Cardiac Arrhythmia Institute at St. David’s Medical Center, Austin, said the authors “should be commended for this prospective study on real-world patients that has yielded highly meaningful data from a clinical standpoint.”
Dr. Natale, who was not involved with the study, said it has “several strong points,” such as a fairly large sample size, exclusive population with a history of AF-related stroke, long follow-up duration, evaluation of fall incidents by blinded experts, and severity of fall assessed by a validated questionnaire.
“This is the first study that directly compared the outcomes of traumatic fall in patients receiving LAAO vs. DOAC,” he said. “Given that history of fall is an independent predictor of bleeding and death, the study findings by Deng et al. offer the hope for a safer life with the LAAO option in the aging, fall-prone AF population.”
The take-home message is that, in patients with history of stroke, LAAO “is a better option, in terms of significantly reduced injury severity and shortened hospital length of stay after traumatic falls,” Dr. Natale said.
This study was supported in part by research grants from Boston Scientific, the Leducq Foundation, and the National Institutes of Health. The authors reported no relevant financial relationships. Dr. Natale is a consultant for Abbott, Baylis, Biosense Webster, Biotronik, Boston Scientific, and Medtronic.
A version of this article appeared on Medscape.com.
Left atrial appendage occlusion (LAAO) is associated with fewer injuries and less bleeding from falls than anticoagulant medications in patients with atrial fibrillation (AF) and a previous stroke, a new cohort study suggests.
Investigators prospectively followed more than 1,250 patients with AF and a previous ischemic stroke. Approximately half underwent LAAO, while the other half were treated with direct oral anticoagulants (DOACs). Patients were followed for close to 2 years.
Slightly more than 20% of patients fell during that period in each group, and , who were not taking anticoagulants. The risk for a major bleed, including an intracranial bleed, was 70% lower in the LAAO group.
LAAO has previously been considered for people at risk of bleeding events – for example, those with gastrointestinal (GI) bleeds, bruising, or intracranial bleeding – but had not yet been studied in those at risk for falls, coauthor Moussa Mansour, MD, professor of medicine, Harvard Medical School, and director of the Atrial Fibrillation Program at Massachusetts General Hospital, Boston, said in an interview.
This is the first study to focus on LAAO specifically for those at risk for falling and demonstrated that the LAAO has utility in this population as well, which is important because the U.S. population is an aging population, and at advanced ages, “people’s balance becomes unsteady and they are at high risk of falling,” he said.
The findings were published online as a research letter in the Journal of the American College of Cardiology.
Multidisciplinary collaboration
“More than one in five of our neurology patients with AF fall – many with devastating consequences – making stroke prevention extremely challenging,” senior author MingMing Ning, MD, MMsc, associate professor of neurology, Harvard Medical School, and director of the Cardio-Neurology and the Clinical Proteomics Research Center at Massachusetts General Hospital, Boston, said in an interview.
“There is a dire need to tailor treatment to keep our patients safe while preventing future strokes,” she said.
Anticoagulants are effective in stroke prevention in these patients but are associated with a higher risk for major bleeding, especially after a fall.
The current prospective observational study recruited 1,266 stroke patients who were treated either with LAAO or DOACs (n = 570 and 696, respectively). Patients were followed for a median of 1.8 years (IQR: 0.9-3.0).
During the follow-up period, 22.6% of LAAO-treated patients and 22.7% of DOAC-treated patients sustained a fall (mean age 78.9 years, 57.4% male and 79.1 years, 52.5% male respectively).
Fall severity, evaluated via the Injury Severity Score, was less in the LAAO vs. the DOAC group, with ISS scores of 1 (IQR 1-4) vs. 4 (IQR 1.75-9).
LAAO was associated with significantly reduced severity of fall-related injuries (OR, –1.09, 95% confidence interval [CI], –1.52 to –0.66; P < .001) – a finding that remained statistically significant after adjustment for confounders such as age, sex, and comorbidities contributing to fall risk, such as hypertension, hyperlipidemia, and diabetes.
The incidence of major trauma (defined as ISS >15) was lower in the LAAO group, compared to the DOAC group (0.8% vs. 6.3%, respectively, P = .026), and LAAO-treated patients had a shorter length of hospital stay, with fewer LAAO patients compared with DOAC patients staying in the hospital for more than 3 days (17% vs. 29.1%, respectively, P = .018).
The risk for major post-fall bleeding was lower in the LAAO vs. the DOAC group (4.7% vs. 15.2%, AOR, 0.29; 95% CI, 0.11-0.73; P = .009) – a finding that included intracranial bleeding (3.1% vs. 9.5%; AOR, 0.29; 95% CI, 0.09-0.90; P = .033).
“Many people are living to advanced ages, where their balance becomes unsteady, and in addition, we have an increase in the prevalence of AF because people are living longer and it’s a disease of the elderly, because we have more hypertension, and we also have more tools to diagnose AF. It’s almost a ‘perfect storm’ situation, and we need effective interventions in this population,” said Dr. Mansour.
Before the study, people at risk for falling were not being considered for LAAO; but now, “we believe they should be considered,” he added. “And although people in the current study had all experienced an ischemic stroke, any patient at risk of a fall will potentially benefit.”
Beyond demonstrating the role of LAAO in reducing the risk of post-fall bleeding injuries, the study – which was conducted by specialists in neurology and cardiology among other fields – highlights the importance of multidisciplinary collaboration, which is “key” for effective stroke prevention, Dr. Ning said.
She emphasized that “we need to learn from our patients and tailor treatment to their needs. A patient’s risk of falling, lifestyle, and medication adherence are all important for individualizing care and improving quality of life.”
Better option
Commenting for this article, Andrea Natale, MD, executive medical director, Texas Cardiac Arrhythmia Institute at St. David’s Medical Center, Austin, said the authors “should be commended for this prospective study on real-world patients that has yielded highly meaningful data from a clinical standpoint.”
Dr. Natale, who was not involved with the study, said it has “several strong points,” such as a fairly large sample size, exclusive population with a history of AF-related stroke, long follow-up duration, evaluation of fall incidents by blinded experts, and severity of fall assessed by a validated questionnaire.
“This is the first study that directly compared the outcomes of traumatic fall in patients receiving LAAO vs. DOAC,” he said. “Given that history of fall is an independent predictor of bleeding and death, the study findings by Deng et al. offer the hope for a safer life with the LAAO option in the aging, fall-prone AF population.”
The take-home message is that, in patients with history of stroke, LAAO “is a better option, in terms of significantly reduced injury severity and shortened hospital length of stay after traumatic falls,” Dr. Natale said.
This study was supported in part by research grants from Boston Scientific, the Leducq Foundation, and the National Institutes of Health. The authors reported no relevant financial relationships. Dr. Natale is a consultant for Abbott, Baylis, Biosense Webster, Biotronik, Boston Scientific, and Medtronic.
A version of this article appeared on Medscape.com.
Left atrial appendage occlusion (LAAO) is associated with fewer injuries and less bleeding from falls than anticoagulant medications in patients with atrial fibrillation (AF) and a previous stroke, a new cohort study suggests.
Investigators prospectively followed more than 1,250 patients with AF and a previous ischemic stroke. Approximately half underwent LAAO, while the other half were treated with direct oral anticoagulants (DOACs). Patients were followed for close to 2 years.
Slightly more than 20% of patients fell during that period in each group, and , who were not taking anticoagulants. The risk for a major bleed, including an intracranial bleed, was 70% lower in the LAAO group.
LAAO has previously been considered for people at risk of bleeding events – for example, those with gastrointestinal (GI) bleeds, bruising, or intracranial bleeding – but had not yet been studied in those at risk for falls, coauthor Moussa Mansour, MD, professor of medicine, Harvard Medical School, and director of the Atrial Fibrillation Program at Massachusetts General Hospital, Boston, said in an interview.
This is the first study to focus on LAAO specifically for those at risk for falling and demonstrated that the LAAO has utility in this population as well, which is important because the U.S. population is an aging population, and at advanced ages, “people’s balance becomes unsteady and they are at high risk of falling,” he said.
The findings were published online as a research letter in the Journal of the American College of Cardiology.
Multidisciplinary collaboration
“More than one in five of our neurology patients with AF fall – many with devastating consequences – making stroke prevention extremely challenging,” senior author MingMing Ning, MD, MMsc, associate professor of neurology, Harvard Medical School, and director of the Cardio-Neurology and the Clinical Proteomics Research Center at Massachusetts General Hospital, Boston, said in an interview.
“There is a dire need to tailor treatment to keep our patients safe while preventing future strokes,” she said.
Anticoagulants are effective in stroke prevention in these patients but are associated with a higher risk for major bleeding, especially after a fall.
The current prospective observational study recruited 1,266 stroke patients who were treated either with LAAO or DOACs (n = 570 and 696, respectively). Patients were followed for a median of 1.8 years (IQR: 0.9-3.0).
During the follow-up period, 22.6% of LAAO-treated patients and 22.7% of DOAC-treated patients sustained a fall (mean age 78.9 years, 57.4% male and 79.1 years, 52.5% male respectively).
Fall severity, evaluated via the Injury Severity Score, was less in the LAAO vs. the DOAC group, with ISS scores of 1 (IQR 1-4) vs. 4 (IQR 1.75-9).
LAAO was associated with significantly reduced severity of fall-related injuries (OR, –1.09, 95% confidence interval [CI], –1.52 to –0.66; P < .001) – a finding that remained statistically significant after adjustment for confounders such as age, sex, and comorbidities contributing to fall risk, such as hypertension, hyperlipidemia, and diabetes.
The incidence of major trauma (defined as ISS >15) was lower in the LAAO group, compared to the DOAC group (0.8% vs. 6.3%, respectively, P = .026), and LAAO-treated patients had a shorter length of hospital stay, with fewer LAAO patients compared with DOAC patients staying in the hospital for more than 3 days (17% vs. 29.1%, respectively, P = .018).
The risk for major post-fall bleeding was lower in the LAAO vs. the DOAC group (4.7% vs. 15.2%, AOR, 0.29; 95% CI, 0.11-0.73; P = .009) – a finding that included intracranial bleeding (3.1% vs. 9.5%; AOR, 0.29; 95% CI, 0.09-0.90; P = .033).
“Many people are living to advanced ages, where their balance becomes unsteady, and in addition, we have an increase in the prevalence of AF because people are living longer and it’s a disease of the elderly, because we have more hypertension, and we also have more tools to diagnose AF. It’s almost a ‘perfect storm’ situation, and we need effective interventions in this population,” said Dr. Mansour.
Before the study, people at risk for falling were not being considered for LAAO; but now, “we believe they should be considered,” he added. “And although people in the current study had all experienced an ischemic stroke, any patient at risk of a fall will potentially benefit.”
Beyond demonstrating the role of LAAO in reducing the risk of post-fall bleeding injuries, the study – which was conducted by specialists in neurology and cardiology among other fields – highlights the importance of multidisciplinary collaboration, which is “key” for effective stroke prevention, Dr. Ning said.
She emphasized that “we need to learn from our patients and tailor treatment to their needs. A patient’s risk of falling, lifestyle, and medication adherence are all important for individualizing care and improving quality of life.”
Better option
Commenting for this article, Andrea Natale, MD, executive medical director, Texas Cardiac Arrhythmia Institute at St. David’s Medical Center, Austin, said the authors “should be commended for this prospective study on real-world patients that has yielded highly meaningful data from a clinical standpoint.”
Dr. Natale, who was not involved with the study, said it has “several strong points,” such as a fairly large sample size, exclusive population with a history of AF-related stroke, long follow-up duration, evaluation of fall incidents by blinded experts, and severity of fall assessed by a validated questionnaire.
“This is the first study that directly compared the outcomes of traumatic fall in patients receiving LAAO vs. DOAC,” he said. “Given that history of fall is an independent predictor of bleeding and death, the study findings by Deng et al. offer the hope for a safer life with the LAAO option in the aging, fall-prone AF population.”
The take-home message is that, in patients with history of stroke, LAAO “is a better option, in terms of significantly reduced injury severity and shortened hospital length of stay after traumatic falls,” Dr. Natale said.
This study was supported in part by research grants from Boston Scientific, the Leducq Foundation, and the National Institutes of Health. The authors reported no relevant financial relationships. Dr. Natale is a consultant for Abbott, Baylis, Biosense Webster, Biotronik, Boston Scientific, and Medtronic.
A version of this article appeared on Medscape.com.
FROM THE JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
Daily aspirin for stroke prevention in healthy elderly should be avoided
according to results from a large randomized trial.
The findings, published in JAMA Network Open, bolster recommendations published in 2022 by the U.S. Preventive Services Task Force against daily aspirin for primary prevention of stroke in older adults and add to a mounting consensus that it should be avoided in the healthy elderly, for whom bleeding risks outweigh potential benefits.
Stroke was a preplanned secondary outcome of the Aspirin in Reducing Events in the Elderly (ASPREE) trial, which randomized 19,114 community-living people in Australia and the United States (56% women, 91% White) to 100 mg. daily aspirin or placebo. Participants were aged 70 and older, with the exception of U.S. Black and Hispanic individuals, who could be as young as 65. Participants did not have disability or known cardiovascular disease at baseline, and blood pressure was adequately controlled.
ASPEE findings
In 2018 the ASPREE authors, led by John McNeil, PhD, of Monash University, Melbourne, published their findings that aspirin did not reduce mortality or cardiovascular events (including stroke) in the same large cohort.
The new analysis, led by Geoffrey Cloud, MB, BS, of Monash University, focuses on stroke and intracranial bleeding outcomes. At 5 years’ follow up, the ASPREE investigators saw no significant reduction in ischemic stroke incidence associated with aspirin (hazard ratio, 0.89; 95% confidence interval, 0.71-1.11), while incidence of all types of intracranial bleeding, including hemorrhagic stroke, was significantly increased (HR, 1.38; 95% CI, 1.03-1.84).
Altogether 108 of participants taking aspirin (1.1%) experienced some form of intracranial bleeding (subdural, extradural, and/or subarachnoid), compared with 79 (0.8%) in the placebo group. Aspirin-treated patients also saw more hemorrhagic stroke (0.5% vs. 0.4%). As the ASPREE investigators had reported in an earlier paper, upper gastrointestinal bleeding occurred in significantly more aspirin-treated patients than those on placebo (HR, 1.87; 95% CI, 1.32-2.66).
“These outcomes may alter the balance of risks and benefits of an antiplatelet drug, especially if given to individuals at low risk in a primary prevention setting. This concern is relevant given the high stroke risk in older individuals, worldwide increases in populations of older individuals, and the importance of evaluating preventive strategies in this age group,” the investigators wrote.
The investigators cited the study’s large size as a strength while noting among its weaknesses that fewer stroke and bleeding events occurred during follow-up than expected, and that not all ischemic stroke events among older participants were thoroughly investigated.
Patients need to know their risk
In an interview, Shlee Song, MD, director of the stroke center at Cedars-Sinai, Los Angeles, said that the new ASPREE findings underscore the importance of careful communication with patients and their families, who may be confused about which risk group they belong to and either cease taking aspirin when it is in fact indicated, or take it when it could harm them.
“We need to be clear for our patients whether these results are relevant to them or not,” Dr. Song said. “People with a history of ischemic stroke need to know aspirin therapy is helpful in reducing risk of another stroke.”
Some patients may come to believe that because their stroke occurred a long time ago, they are in a lower-risk group. “But people need to understand that with a history of a heart attack or stroke, you’re always a separate group,” Dr. Song said. “Our job is also surveillance screening – have you had a fall this past year? Have you had a change in bowel movements? The bleeding events seen in ASPREE include bleeding in the head and bleeding in the gut.”
A key issue to stress with patients, Dr. Song said, is blood pressure management. “Patients might take aspirin because a family member had a stroke, without controlling blood pressure first. That could be the perfect storm for a head bleed: uncontrolled hypertension and an antiplatelet agent.”
The ASPREE study was funded by the National Institutes of Health in the United States and Monash University and the Victorian Cancer Agency in Australia. Three coauthors reported receiving funding or fees from drug manufacturers. Dr. Song disclosed no financial conflicts related to her comments.
according to results from a large randomized trial.
The findings, published in JAMA Network Open, bolster recommendations published in 2022 by the U.S. Preventive Services Task Force against daily aspirin for primary prevention of stroke in older adults and add to a mounting consensus that it should be avoided in the healthy elderly, for whom bleeding risks outweigh potential benefits.
Stroke was a preplanned secondary outcome of the Aspirin in Reducing Events in the Elderly (ASPREE) trial, which randomized 19,114 community-living people in Australia and the United States (56% women, 91% White) to 100 mg. daily aspirin or placebo. Participants were aged 70 and older, with the exception of U.S. Black and Hispanic individuals, who could be as young as 65. Participants did not have disability or known cardiovascular disease at baseline, and blood pressure was adequately controlled.
ASPEE findings
In 2018 the ASPREE authors, led by John McNeil, PhD, of Monash University, Melbourne, published their findings that aspirin did not reduce mortality or cardiovascular events (including stroke) in the same large cohort.
The new analysis, led by Geoffrey Cloud, MB, BS, of Monash University, focuses on stroke and intracranial bleeding outcomes. At 5 years’ follow up, the ASPREE investigators saw no significant reduction in ischemic stroke incidence associated with aspirin (hazard ratio, 0.89; 95% confidence interval, 0.71-1.11), while incidence of all types of intracranial bleeding, including hemorrhagic stroke, was significantly increased (HR, 1.38; 95% CI, 1.03-1.84).
Altogether 108 of participants taking aspirin (1.1%) experienced some form of intracranial bleeding (subdural, extradural, and/or subarachnoid), compared with 79 (0.8%) in the placebo group. Aspirin-treated patients also saw more hemorrhagic stroke (0.5% vs. 0.4%). As the ASPREE investigators had reported in an earlier paper, upper gastrointestinal bleeding occurred in significantly more aspirin-treated patients than those on placebo (HR, 1.87; 95% CI, 1.32-2.66).
“These outcomes may alter the balance of risks and benefits of an antiplatelet drug, especially if given to individuals at low risk in a primary prevention setting. This concern is relevant given the high stroke risk in older individuals, worldwide increases in populations of older individuals, and the importance of evaluating preventive strategies in this age group,” the investigators wrote.
The investigators cited the study’s large size as a strength while noting among its weaknesses that fewer stroke and bleeding events occurred during follow-up than expected, and that not all ischemic stroke events among older participants were thoroughly investigated.
Patients need to know their risk
In an interview, Shlee Song, MD, director of the stroke center at Cedars-Sinai, Los Angeles, said that the new ASPREE findings underscore the importance of careful communication with patients and their families, who may be confused about which risk group they belong to and either cease taking aspirin when it is in fact indicated, or take it when it could harm them.
“We need to be clear for our patients whether these results are relevant to them or not,” Dr. Song said. “People with a history of ischemic stroke need to know aspirin therapy is helpful in reducing risk of another stroke.”
Some patients may come to believe that because their stroke occurred a long time ago, they are in a lower-risk group. “But people need to understand that with a history of a heart attack or stroke, you’re always a separate group,” Dr. Song said. “Our job is also surveillance screening – have you had a fall this past year? Have you had a change in bowel movements? The bleeding events seen in ASPREE include bleeding in the head and bleeding in the gut.”
A key issue to stress with patients, Dr. Song said, is blood pressure management. “Patients might take aspirin because a family member had a stroke, without controlling blood pressure first. That could be the perfect storm for a head bleed: uncontrolled hypertension and an antiplatelet agent.”
The ASPREE study was funded by the National Institutes of Health in the United States and Monash University and the Victorian Cancer Agency in Australia. Three coauthors reported receiving funding or fees from drug manufacturers. Dr. Song disclosed no financial conflicts related to her comments.
according to results from a large randomized trial.
The findings, published in JAMA Network Open, bolster recommendations published in 2022 by the U.S. Preventive Services Task Force against daily aspirin for primary prevention of stroke in older adults and add to a mounting consensus that it should be avoided in the healthy elderly, for whom bleeding risks outweigh potential benefits.
Stroke was a preplanned secondary outcome of the Aspirin in Reducing Events in the Elderly (ASPREE) trial, which randomized 19,114 community-living people in Australia and the United States (56% women, 91% White) to 100 mg. daily aspirin or placebo. Participants were aged 70 and older, with the exception of U.S. Black and Hispanic individuals, who could be as young as 65. Participants did not have disability or known cardiovascular disease at baseline, and blood pressure was adequately controlled.
ASPEE findings
In 2018 the ASPREE authors, led by John McNeil, PhD, of Monash University, Melbourne, published their findings that aspirin did not reduce mortality or cardiovascular events (including stroke) in the same large cohort.
The new analysis, led by Geoffrey Cloud, MB, BS, of Monash University, focuses on stroke and intracranial bleeding outcomes. At 5 years’ follow up, the ASPREE investigators saw no significant reduction in ischemic stroke incidence associated with aspirin (hazard ratio, 0.89; 95% confidence interval, 0.71-1.11), while incidence of all types of intracranial bleeding, including hemorrhagic stroke, was significantly increased (HR, 1.38; 95% CI, 1.03-1.84).
Altogether 108 of participants taking aspirin (1.1%) experienced some form of intracranial bleeding (subdural, extradural, and/or subarachnoid), compared with 79 (0.8%) in the placebo group. Aspirin-treated patients also saw more hemorrhagic stroke (0.5% vs. 0.4%). As the ASPREE investigators had reported in an earlier paper, upper gastrointestinal bleeding occurred in significantly more aspirin-treated patients than those on placebo (HR, 1.87; 95% CI, 1.32-2.66).
“These outcomes may alter the balance of risks and benefits of an antiplatelet drug, especially if given to individuals at low risk in a primary prevention setting. This concern is relevant given the high stroke risk in older individuals, worldwide increases in populations of older individuals, and the importance of evaluating preventive strategies in this age group,” the investigators wrote.
The investigators cited the study’s large size as a strength while noting among its weaknesses that fewer stroke and bleeding events occurred during follow-up than expected, and that not all ischemic stroke events among older participants were thoroughly investigated.
Patients need to know their risk
In an interview, Shlee Song, MD, director of the stroke center at Cedars-Sinai, Los Angeles, said that the new ASPREE findings underscore the importance of careful communication with patients and their families, who may be confused about which risk group they belong to and either cease taking aspirin when it is in fact indicated, or take it when it could harm them.
“We need to be clear for our patients whether these results are relevant to them or not,” Dr. Song said. “People with a history of ischemic stroke need to know aspirin therapy is helpful in reducing risk of another stroke.”
Some patients may come to believe that because their stroke occurred a long time ago, they are in a lower-risk group. “But people need to understand that with a history of a heart attack or stroke, you’re always a separate group,” Dr. Song said. “Our job is also surveillance screening – have you had a fall this past year? Have you had a change in bowel movements? The bleeding events seen in ASPREE include bleeding in the head and bleeding in the gut.”
A key issue to stress with patients, Dr. Song said, is blood pressure management. “Patients might take aspirin because a family member had a stroke, without controlling blood pressure first. That could be the perfect storm for a head bleed: uncontrolled hypertension and an antiplatelet agent.”
The ASPREE study was funded by the National Institutes of Health in the United States and Monash University and the Victorian Cancer Agency in Australia. Three coauthors reported receiving funding or fees from drug manufacturers. Dr. Song disclosed no financial conflicts related to her comments.
FROM JAMA NETWORK OPEN
Research casts doubt on value of daily aspirin for healthy adults
Daily use of low-dose aspirin offers no significant protection against stroke and was linked to a higher rate of bleeding in the brain, according to new research published in JAMA.
The research matches other evidence advising that healthy older adults without a history of heart conditions or warning signs of stroke should not take low-dose aspirin.
The findings also support the recommendation from the U.S. Preventive Services Task Force that low-dose aspirin should not be prescribed for preventing a first heart attack or stroke in healthy older adults, The New York Times reported.
“We can be very emphatic that healthy people who are not on aspirin and do not have multiple risk factors should not be starting it now,” said Randall Stafford, MD, of Stanford (Calif.) University, who was not involved in the study, in the Times.
It’s not as clear for others, he said.
“The longer you’ve been on aspirin and the more risk factors you have for heart attacks and strokes, the murkier it gets,” he said.
Some cardiac and stroke experts say daily aspirin should remain part of the regimen for people who have had a heart attack or stroke.
The JAMA report was based on data from a randomized control trial of 19,000 people from Australia and America. Participants were over the age of 70 and did not have heart disease.
The data covered an average of almost 4.7 years and revealed that aspirin lowered the rate of ischemic stroke but not significantly. An ischemic stroke happens when a clot forms in a blood vessel that sends blood to the brain.
There was also a 38% higher rate of brain bleeds for people who took aspirin daily, compared with those who took a placebo.
The Times wrote, “In the past, some doctors regarded aspirin as something of a wonder drug, capable of protecting healthy patients against a future heart attack or stroke. But recent studies have shown that the powerful drug has limited protective power among people who have not yet had such an event, and it comes with dangerous side effects.”
A version of this article first appeared on WebMD.com.
Daily use of low-dose aspirin offers no significant protection against stroke and was linked to a higher rate of bleeding in the brain, according to new research published in JAMA.
The research matches other evidence advising that healthy older adults without a history of heart conditions or warning signs of stroke should not take low-dose aspirin.
The findings also support the recommendation from the U.S. Preventive Services Task Force that low-dose aspirin should not be prescribed for preventing a first heart attack or stroke in healthy older adults, The New York Times reported.
“We can be very emphatic that healthy people who are not on aspirin and do not have multiple risk factors should not be starting it now,” said Randall Stafford, MD, of Stanford (Calif.) University, who was not involved in the study, in the Times.
It’s not as clear for others, he said.
“The longer you’ve been on aspirin and the more risk factors you have for heart attacks and strokes, the murkier it gets,” he said.
Some cardiac and stroke experts say daily aspirin should remain part of the regimen for people who have had a heart attack or stroke.
The JAMA report was based on data from a randomized control trial of 19,000 people from Australia and America. Participants were over the age of 70 and did not have heart disease.
The data covered an average of almost 4.7 years and revealed that aspirin lowered the rate of ischemic stroke but not significantly. An ischemic stroke happens when a clot forms in a blood vessel that sends blood to the brain.
There was also a 38% higher rate of brain bleeds for people who took aspirin daily, compared with those who took a placebo.
The Times wrote, “In the past, some doctors regarded aspirin as something of a wonder drug, capable of protecting healthy patients against a future heart attack or stroke. But recent studies have shown that the powerful drug has limited protective power among people who have not yet had such an event, and it comes with dangerous side effects.”
A version of this article first appeared on WebMD.com.
Daily use of low-dose aspirin offers no significant protection against stroke and was linked to a higher rate of bleeding in the brain, according to new research published in JAMA.
The research matches other evidence advising that healthy older adults without a history of heart conditions or warning signs of stroke should not take low-dose aspirin.
The findings also support the recommendation from the U.S. Preventive Services Task Force that low-dose aspirin should not be prescribed for preventing a first heart attack or stroke in healthy older adults, The New York Times reported.
“We can be very emphatic that healthy people who are not on aspirin and do not have multiple risk factors should not be starting it now,” said Randall Stafford, MD, of Stanford (Calif.) University, who was not involved in the study, in the Times.
It’s not as clear for others, he said.
“The longer you’ve been on aspirin and the more risk factors you have for heart attacks and strokes, the murkier it gets,” he said.
Some cardiac and stroke experts say daily aspirin should remain part of the regimen for people who have had a heart attack or stroke.
The JAMA report was based on data from a randomized control trial of 19,000 people from Australia and America. Participants were over the age of 70 and did not have heart disease.
The data covered an average of almost 4.7 years and revealed that aspirin lowered the rate of ischemic stroke but not significantly. An ischemic stroke happens when a clot forms in a blood vessel that sends blood to the brain.
There was also a 38% higher rate of brain bleeds for people who took aspirin daily, compared with those who took a placebo.
The Times wrote, “In the past, some doctors regarded aspirin as something of a wonder drug, capable of protecting healthy patients against a future heart attack or stroke. But recent studies have shown that the powerful drug has limited protective power among people who have not yet had such an event, and it comes with dangerous side effects.”
A version of this article first appeared on WebMD.com.
FROM JAMA
Global burden of brain disorders surpasses cardiovascular disease and cancer
– at huge cost to health care systems and society, an analysis of data from the most recent Global Burden of Disease (GBD) study shows.
“The burden of brain conditions will increase as populations continue to grow and age,” said study presenter Shayla Smith, MPH, an epidemiologist at the Institute for Health Metrics and Evaluation, the University of Washington, Seattle, in a press release.
“By 2050, more than 50 million people will be aged 65-79,” she explained, adding that the COVID-19 pandemic “has also influenced the prevalence of mental disorders globally, as people were forced to isolate and social networks broke down.”
Other factors related to brain disorders, she noted, include education level, obesity, and smoking.
“There’s still research to be done on what is the most effective way to maintain brain health, but some literature suggests a healthy brain can be achieved through a healthy lifestyle of managing conditions such as high blood pressure and diabetes, limiting alcohol consumption and smoking, prioritizing sleep, eating healthy, and staying physically and mentally active,” said Ms. Smith.
The findings were presented at the annual meeting of the Congress of the European Academy of Neurology.
An ‘ambitious exercise’
Coinvestigator Xaviera Steele, also from the IHME, told press conference attendees that the institute was established at the University of Washington in 2007 with the aim of “standardizing the measurement of health outcomes around the world and for all health conditions.”
A central part of that is the GBD study, “which is a very ambitious exercise in descriptive epidemiology in an effort to systematically quantify health loss” due to disease, injury, and risk factors over time, stratified by country, region, age, and sex. In addition, researchers are mapping and projecting trends over the next century and are estimating disease expenditure by country, by type of expense, and by condition “to derive a health care access and quality score for each health system in the world,” Ms. Steele said.
They are also estimating exposure to risk factors, how those risk factors contribute to health burden, and associated health outcomes by race and ethnicity to reflect the “disparities that we know are very prevalent in countries such as the United States.” From that work, Ms. Steele said that brain health and related conditions “do emerge as one of the more pressing challenges of the 21st century.”
Increase in dementia, mental health conditions
The data, which were gathered from 200,000 sources by the IHME, indicate that the number of individuals aged 65 years or older will increase by 350% by 2100. Ms. Steele underlined that “policy action will be needed to help families, who will struggle to provide high-quality care for their loved ones with dementia at a reasonable cost.”
The IHME calculates that in Europe health care spending on Alzheimer’s disease will increase by 226% between 2015 and 2040.
Turning to other conditions, Ms. Steele showed that since 1990, the number of individuals living with anxiety in the European region has increased by 14%, while the number living with depressive disorders has gone up by 13%.
Worldwide, the figures are even starker. Depression is estimated to affect 300 million people across the globe, which represents a 71% increase since 1990. The number of strokes increased by 95% over the same period.
Nevertheless, the “impact of brain conditions such as stroke has decreased since the 1990s due to improved treatments available,” Ms. Smith noted in the press release.
To estimate the toll caused by brain conditions, including neurologic disorders, mental disorders, cerebrovascular disease, brain cancer, brain injuries, and select infectious conditions, the researchers calculated disability-adjusted life years (DALYs).
This, Ms. Smith explained in her presentation, “captures the morbidity and mortality associated with brain conditions” and is adjusted for patient location, age, and sex.
The investigators found that, globally, brain conditions accounted for more than 15% of all health loss in 2021, at 406 DALYs – more than the 206 million DALYs that were associated with cancer, and the 402 million that were linked to cardiovascular disease.
This health loss is associated with a $1.22 trillion loss in income for people living with health disorders worldwide and accounts for $1.14 trillion in direct health care costs.
The burden of mental disorders, neurologic conditions, and stroke is expected to increase dramatically between now and 2050, said Ms. Smith, who noted that health loss linked to brain conditions is higher in younger patients. This will create “new challenges for health systems, employers, patients, and families,” she said in the press release.
“Our goal is to see an improved prevention and treatment landscape for other brain conditions and reverse the growing health loss that we are currently forecasting.”
Worrying increase in stroke
Jurgita Valaikiene, MD, PhD, center of neurology, clinic of neurology and neurosurgery, Vilnius (Lithuania) University Faculty of Medicine, who chaired the session, was taken aback by the findings, particularly by the worldwide increase in stroke cases.
“I work in stroke,” she said, and “we spend a lot of time on the diagnosis of stroke” and its prevention. “We try to be faster, to catch asymptomatic stenosis in the neck or head, and to apply the best medical treatment to avoid a stroke. But despite that, the numbers are increasing. I understand the population is getting older ... but still it’s a huge number.”
Dr. Valaikiene pointed out that stroke is not necessarily a condition of aging, insofar as increasing age “is not related directly to stenosis in the neck. “For example, we can have healthier vessels in older age and unhealthy vessels, with high-grade stenosis, in someone aged 30 or 40 years.”
“There are a lot of risk factors, such as smoking, physical activity, and so on. It depends on the individual,” she added.
The study was funded by the Institute for Health Metrics and Evaluation at the University of Washington. The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
– at huge cost to health care systems and society, an analysis of data from the most recent Global Burden of Disease (GBD) study shows.
“The burden of brain conditions will increase as populations continue to grow and age,” said study presenter Shayla Smith, MPH, an epidemiologist at the Institute for Health Metrics and Evaluation, the University of Washington, Seattle, in a press release.
“By 2050, more than 50 million people will be aged 65-79,” she explained, adding that the COVID-19 pandemic “has also influenced the prevalence of mental disorders globally, as people were forced to isolate and social networks broke down.”
Other factors related to brain disorders, she noted, include education level, obesity, and smoking.
“There’s still research to be done on what is the most effective way to maintain brain health, but some literature suggests a healthy brain can be achieved through a healthy lifestyle of managing conditions such as high blood pressure and diabetes, limiting alcohol consumption and smoking, prioritizing sleep, eating healthy, and staying physically and mentally active,” said Ms. Smith.
The findings were presented at the annual meeting of the Congress of the European Academy of Neurology.
An ‘ambitious exercise’
Coinvestigator Xaviera Steele, also from the IHME, told press conference attendees that the institute was established at the University of Washington in 2007 with the aim of “standardizing the measurement of health outcomes around the world and for all health conditions.”
A central part of that is the GBD study, “which is a very ambitious exercise in descriptive epidemiology in an effort to systematically quantify health loss” due to disease, injury, and risk factors over time, stratified by country, region, age, and sex. In addition, researchers are mapping and projecting trends over the next century and are estimating disease expenditure by country, by type of expense, and by condition “to derive a health care access and quality score for each health system in the world,” Ms. Steele said.
They are also estimating exposure to risk factors, how those risk factors contribute to health burden, and associated health outcomes by race and ethnicity to reflect the “disparities that we know are very prevalent in countries such as the United States.” From that work, Ms. Steele said that brain health and related conditions “do emerge as one of the more pressing challenges of the 21st century.”
Increase in dementia, mental health conditions
The data, which were gathered from 200,000 sources by the IHME, indicate that the number of individuals aged 65 years or older will increase by 350% by 2100. Ms. Steele underlined that “policy action will be needed to help families, who will struggle to provide high-quality care for their loved ones with dementia at a reasonable cost.”
The IHME calculates that in Europe health care spending on Alzheimer’s disease will increase by 226% between 2015 and 2040.
Turning to other conditions, Ms. Steele showed that since 1990, the number of individuals living with anxiety in the European region has increased by 14%, while the number living with depressive disorders has gone up by 13%.
Worldwide, the figures are even starker. Depression is estimated to affect 300 million people across the globe, which represents a 71% increase since 1990. The number of strokes increased by 95% over the same period.
Nevertheless, the “impact of brain conditions such as stroke has decreased since the 1990s due to improved treatments available,” Ms. Smith noted in the press release.
To estimate the toll caused by brain conditions, including neurologic disorders, mental disorders, cerebrovascular disease, brain cancer, brain injuries, and select infectious conditions, the researchers calculated disability-adjusted life years (DALYs).
This, Ms. Smith explained in her presentation, “captures the morbidity and mortality associated with brain conditions” and is adjusted for patient location, age, and sex.
The investigators found that, globally, brain conditions accounted for more than 15% of all health loss in 2021, at 406 DALYs – more than the 206 million DALYs that were associated with cancer, and the 402 million that were linked to cardiovascular disease.
This health loss is associated with a $1.22 trillion loss in income for people living with health disorders worldwide and accounts for $1.14 trillion in direct health care costs.
The burden of mental disorders, neurologic conditions, and stroke is expected to increase dramatically between now and 2050, said Ms. Smith, who noted that health loss linked to brain conditions is higher in younger patients. This will create “new challenges for health systems, employers, patients, and families,” she said in the press release.
“Our goal is to see an improved prevention and treatment landscape for other brain conditions and reverse the growing health loss that we are currently forecasting.”
Worrying increase in stroke
Jurgita Valaikiene, MD, PhD, center of neurology, clinic of neurology and neurosurgery, Vilnius (Lithuania) University Faculty of Medicine, who chaired the session, was taken aback by the findings, particularly by the worldwide increase in stroke cases.
“I work in stroke,” she said, and “we spend a lot of time on the diagnosis of stroke” and its prevention. “We try to be faster, to catch asymptomatic stenosis in the neck or head, and to apply the best medical treatment to avoid a stroke. But despite that, the numbers are increasing. I understand the population is getting older ... but still it’s a huge number.”
Dr. Valaikiene pointed out that stroke is not necessarily a condition of aging, insofar as increasing age “is not related directly to stenosis in the neck. “For example, we can have healthier vessels in older age and unhealthy vessels, with high-grade stenosis, in someone aged 30 or 40 years.”
“There are a lot of risk factors, such as smoking, physical activity, and so on. It depends on the individual,” she added.
The study was funded by the Institute for Health Metrics and Evaluation at the University of Washington. The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
– at huge cost to health care systems and society, an analysis of data from the most recent Global Burden of Disease (GBD) study shows.
“The burden of brain conditions will increase as populations continue to grow and age,” said study presenter Shayla Smith, MPH, an epidemiologist at the Institute for Health Metrics and Evaluation, the University of Washington, Seattle, in a press release.
“By 2050, more than 50 million people will be aged 65-79,” she explained, adding that the COVID-19 pandemic “has also influenced the prevalence of mental disorders globally, as people were forced to isolate and social networks broke down.”
Other factors related to brain disorders, she noted, include education level, obesity, and smoking.
“There’s still research to be done on what is the most effective way to maintain brain health, but some literature suggests a healthy brain can be achieved through a healthy lifestyle of managing conditions such as high blood pressure and diabetes, limiting alcohol consumption and smoking, prioritizing sleep, eating healthy, and staying physically and mentally active,” said Ms. Smith.
The findings were presented at the annual meeting of the Congress of the European Academy of Neurology.
An ‘ambitious exercise’
Coinvestigator Xaviera Steele, also from the IHME, told press conference attendees that the institute was established at the University of Washington in 2007 with the aim of “standardizing the measurement of health outcomes around the world and for all health conditions.”
A central part of that is the GBD study, “which is a very ambitious exercise in descriptive epidemiology in an effort to systematically quantify health loss” due to disease, injury, and risk factors over time, stratified by country, region, age, and sex. In addition, researchers are mapping and projecting trends over the next century and are estimating disease expenditure by country, by type of expense, and by condition “to derive a health care access and quality score for each health system in the world,” Ms. Steele said.
They are also estimating exposure to risk factors, how those risk factors contribute to health burden, and associated health outcomes by race and ethnicity to reflect the “disparities that we know are very prevalent in countries such as the United States.” From that work, Ms. Steele said that brain health and related conditions “do emerge as one of the more pressing challenges of the 21st century.”
Increase in dementia, mental health conditions
The data, which were gathered from 200,000 sources by the IHME, indicate that the number of individuals aged 65 years or older will increase by 350% by 2100. Ms. Steele underlined that “policy action will be needed to help families, who will struggle to provide high-quality care for their loved ones with dementia at a reasonable cost.”
The IHME calculates that in Europe health care spending on Alzheimer’s disease will increase by 226% between 2015 and 2040.
Turning to other conditions, Ms. Steele showed that since 1990, the number of individuals living with anxiety in the European region has increased by 14%, while the number living with depressive disorders has gone up by 13%.
Worldwide, the figures are even starker. Depression is estimated to affect 300 million people across the globe, which represents a 71% increase since 1990. The number of strokes increased by 95% over the same period.
Nevertheless, the “impact of brain conditions such as stroke has decreased since the 1990s due to improved treatments available,” Ms. Smith noted in the press release.
To estimate the toll caused by brain conditions, including neurologic disorders, mental disorders, cerebrovascular disease, brain cancer, brain injuries, and select infectious conditions, the researchers calculated disability-adjusted life years (DALYs).
This, Ms. Smith explained in her presentation, “captures the morbidity and mortality associated with brain conditions” and is adjusted for patient location, age, and sex.
The investigators found that, globally, brain conditions accounted for more than 15% of all health loss in 2021, at 406 DALYs – more than the 206 million DALYs that were associated with cancer, and the 402 million that were linked to cardiovascular disease.
This health loss is associated with a $1.22 trillion loss in income for people living with health disorders worldwide and accounts for $1.14 trillion in direct health care costs.
The burden of mental disorders, neurologic conditions, and stroke is expected to increase dramatically between now and 2050, said Ms. Smith, who noted that health loss linked to brain conditions is higher in younger patients. This will create “new challenges for health systems, employers, patients, and families,” she said in the press release.
“Our goal is to see an improved prevention and treatment landscape for other brain conditions and reverse the growing health loss that we are currently forecasting.”
Worrying increase in stroke
Jurgita Valaikiene, MD, PhD, center of neurology, clinic of neurology and neurosurgery, Vilnius (Lithuania) University Faculty of Medicine, who chaired the session, was taken aback by the findings, particularly by the worldwide increase in stroke cases.
“I work in stroke,” she said, and “we spend a lot of time on the diagnosis of stroke” and its prevention. “We try to be faster, to catch asymptomatic stenosis in the neck or head, and to apply the best medical treatment to avoid a stroke. But despite that, the numbers are increasing. I understand the population is getting older ... but still it’s a huge number.”
Dr. Valaikiene pointed out that stroke is not necessarily a condition of aging, insofar as increasing age “is not related directly to stenosis in the neck. “For example, we can have healthier vessels in older age and unhealthy vessels, with high-grade stenosis, in someone aged 30 or 40 years.”
“There are a lot of risk factors, such as smoking, physical activity, and so on. It depends on the individual,” she added.
The study was funded by the Institute for Health Metrics and Evaluation at the University of Washington. The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Women with atrial fibrillation more likely to develop dementia
New data suggest a significantly stronger link in women compared with men between atrial fibrillation (AF) and mild cognitive impairment (MCI) and dementia.
“Our findings imply that women with AF may be at higher risk for MCI and dementia with potentially more rapid disease progression from normal cognition to MCI or dementia than women without AF or men with and without AF,” wrote authors of a new study led by Kathryn A. Wood, PhD, RN, Neil Hodgson Woodruff School of Nursing at Emory University in Atlanta.
The findings were published online in Alzheimer’s & Dementia.
Researchers used the National Alzheimer’s Coordinating Center data with 43,630 patients and analyzed sex differences between men and women with AF and their performance on neuropsychological tests and cognitive disease progression.
Higher odds of dementia, MCI in women
According to the paper, AF is associated with higher odds of dementia (odds ratio [OR], 3.00; 95% confidence interval [CI], 1.22-7.37) in women and MCI in women (OR, 3.43; 95% CI, 1.55-7.55) compared with men.
Women with AF and normal cognition at baseline had a higher risk of disease progression (hazard ratio [HR], 1.26; 95% CI, 1.06-1.50) from normal to MCI and from MCI to vascular dementia (HR, 3.27; 95% CI, 1.89-5.65) than that of men with AF or men and women without AF.
AF is a major public health problem linked with stroke and heart failure, and is an independent risk factor of increased mortality. It is associated with higher risk of cognitive impairment and dementia independent of stroke history.
Cognitive screening for AF patients
The authors wrote that cognitive screening, especially in women, should be part of yearly cardiology visits for patients with AF to help identify early those at highest risk for cognitive disease.
T. Jared Bunch, MD, professor of medicine in the division of cardiovascular medicine at University of Utah in Salt Lake City, said in an interview, “We have learned that how we treat atrial fibrillation can influence risk.”
First, he said, outcomes, including brain health, are better when rhythm control approaches are used within the first year of diagnosis.
“Restoring a normal heart rhythm improves brain perfusion and cognitive function. Next, aggressive rhythm control – such as catheter ablation – is associated with much lower long-term risks of dementia in the [patients]. Finally, early and effective use of anticoagulation in patients with atrial fibrillation lowers risk of stroke, dementia, and cognitive decline.”
Several factors unknown
Dr. Bunch said there are some unknowns in the study, such as how long patients were in atrial fibrillation.
He said one way to address the inequities is to refer women earlier as women are often referred later in disease to specialty care, which can have consequences.
He said it is not known how many people underwent early and effective rhythm control.
“Women also are less likely to receive catheter ablation, a cardioversion, or be placed on antiarrhythmic drugs,” said Dr. Bunch, who was not part of the study. “These also represent potential opportunities to improve outcomes by treating the rhythm in a similar and aggressive manner in both men and women.”
Also unknown is how many people were on effective oral anticoagulation, Dr. Bunch noted.
The study importantly highlights a significant problem surrounding the care of women with AF, he said, but there are strategies to improve outcomes.
In addition to earlier screening and referral for women, providers should recognize that men and women may present differently with different AF symptoms. He added that physicians should offer catheter ablation, the most effective treatment, equally to men and women who are candidates.
In all people, he said, it’s important “to start anticoagulation very early in the disease to lower the risk of micro- and macrothrombotic events that lead to poor brain health and function.”
The study authors and Dr. Bunch declared no relevant financial relationships.
New data suggest a significantly stronger link in women compared with men between atrial fibrillation (AF) and mild cognitive impairment (MCI) and dementia.
“Our findings imply that women with AF may be at higher risk for MCI and dementia with potentially more rapid disease progression from normal cognition to MCI or dementia than women without AF or men with and without AF,” wrote authors of a new study led by Kathryn A. Wood, PhD, RN, Neil Hodgson Woodruff School of Nursing at Emory University in Atlanta.
The findings were published online in Alzheimer’s & Dementia.
Researchers used the National Alzheimer’s Coordinating Center data with 43,630 patients and analyzed sex differences between men and women with AF and their performance on neuropsychological tests and cognitive disease progression.
Higher odds of dementia, MCI in women
According to the paper, AF is associated with higher odds of dementia (odds ratio [OR], 3.00; 95% confidence interval [CI], 1.22-7.37) in women and MCI in women (OR, 3.43; 95% CI, 1.55-7.55) compared with men.
Women with AF and normal cognition at baseline had a higher risk of disease progression (hazard ratio [HR], 1.26; 95% CI, 1.06-1.50) from normal to MCI and from MCI to vascular dementia (HR, 3.27; 95% CI, 1.89-5.65) than that of men with AF or men and women without AF.
AF is a major public health problem linked with stroke and heart failure, and is an independent risk factor of increased mortality. It is associated with higher risk of cognitive impairment and dementia independent of stroke history.
Cognitive screening for AF patients
The authors wrote that cognitive screening, especially in women, should be part of yearly cardiology visits for patients with AF to help identify early those at highest risk for cognitive disease.
T. Jared Bunch, MD, professor of medicine in the division of cardiovascular medicine at University of Utah in Salt Lake City, said in an interview, “We have learned that how we treat atrial fibrillation can influence risk.”
First, he said, outcomes, including brain health, are better when rhythm control approaches are used within the first year of diagnosis.
“Restoring a normal heart rhythm improves brain perfusion and cognitive function. Next, aggressive rhythm control – such as catheter ablation – is associated with much lower long-term risks of dementia in the [patients]. Finally, early and effective use of anticoagulation in patients with atrial fibrillation lowers risk of stroke, dementia, and cognitive decline.”
Several factors unknown
Dr. Bunch said there are some unknowns in the study, such as how long patients were in atrial fibrillation.
He said one way to address the inequities is to refer women earlier as women are often referred later in disease to specialty care, which can have consequences.
He said it is not known how many people underwent early and effective rhythm control.
“Women also are less likely to receive catheter ablation, a cardioversion, or be placed on antiarrhythmic drugs,” said Dr. Bunch, who was not part of the study. “These also represent potential opportunities to improve outcomes by treating the rhythm in a similar and aggressive manner in both men and women.”
Also unknown is how many people were on effective oral anticoagulation, Dr. Bunch noted.
The study importantly highlights a significant problem surrounding the care of women with AF, he said, but there are strategies to improve outcomes.
In addition to earlier screening and referral for women, providers should recognize that men and women may present differently with different AF symptoms. He added that physicians should offer catheter ablation, the most effective treatment, equally to men and women who are candidates.
In all people, he said, it’s important “to start anticoagulation very early in the disease to lower the risk of micro- and macrothrombotic events that lead to poor brain health and function.”
The study authors and Dr. Bunch declared no relevant financial relationships.
New data suggest a significantly stronger link in women compared with men between atrial fibrillation (AF) and mild cognitive impairment (MCI) and dementia.
“Our findings imply that women with AF may be at higher risk for MCI and dementia with potentially more rapid disease progression from normal cognition to MCI or dementia than women without AF or men with and without AF,” wrote authors of a new study led by Kathryn A. Wood, PhD, RN, Neil Hodgson Woodruff School of Nursing at Emory University in Atlanta.
The findings were published online in Alzheimer’s & Dementia.
Researchers used the National Alzheimer’s Coordinating Center data with 43,630 patients and analyzed sex differences between men and women with AF and their performance on neuropsychological tests and cognitive disease progression.
Higher odds of dementia, MCI in women
According to the paper, AF is associated with higher odds of dementia (odds ratio [OR], 3.00; 95% confidence interval [CI], 1.22-7.37) in women and MCI in women (OR, 3.43; 95% CI, 1.55-7.55) compared with men.
Women with AF and normal cognition at baseline had a higher risk of disease progression (hazard ratio [HR], 1.26; 95% CI, 1.06-1.50) from normal to MCI and from MCI to vascular dementia (HR, 3.27; 95% CI, 1.89-5.65) than that of men with AF or men and women without AF.
AF is a major public health problem linked with stroke and heart failure, and is an independent risk factor of increased mortality. It is associated with higher risk of cognitive impairment and dementia independent of stroke history.
Cognitive screening for AF patients
The authors wrote that cognitive screening, especially in women, should be part of yearly cardiology visits for patients with AF to help identify early those at highest risk for cognitive disease.
T. Jared Bunch, MD, professor of medicine in the division of cardiovascular medicine at University of Utah in Salt Lake City, said in an interview, “We have learned that how we treat atrial fibrillation can influence risk.”
First, he said, outcomes, including brain health, are better when rhythm control approaches are used within the first year of diagnosis.
“Restoring a normal heart rhythm improves brain perfusion and cognitive function. Next, aggressive rhythm control – such as catheter ablation – is associated with much lower long-term risks of dementia in the [patients]. Finally, early and effective use of anticoagulation in patients with atrial fibrillation lowers risk of stroke, dementia, and cognitive decline.”
Several factors unknown
Dr. Bunch said there are some unknowns in the study, such as how long patients were in atrial fibrillation.
He said one way to address the inequities is to refer women earlier as women are often referred later in disease to specialty care, which can have consequences.
He said it is not known how many people underwent early and effective rhythm control.
“Women also are less likely to receive catheter ablation, a cardioversion, or be placed on antiarrhythmic drugs,” said Dr. Bunch, who was not part of the study. “These also represent potential opportunities to improve outcomes by treating the rhythm in a similar and aggressive manner in both men and women.”
Also unknown is how many people were on effective oral anticoagulation, Dr. Bunch noted.
The study importantly highlights a significant problem surrounding the care of women with AF, he said, but there are strategies to improve outcomes.
In addition to earlier screening and referral for women, providers should recognize that men and women may present differently with different AF symptoms. He added that physicians should offer catheter ablation, the most effective treatment, equally to men and women who are candidates.
In all people, he said, it’s important “to start anticoagulation very early in the disease to lower the risk of micro- and macrothrombotic events that lead to poor brain health and function.”
The study authors and Dr. Bunch declared no relevant financial relationships.
FROM ALZHEIMER’S & DEMENTIA
Are periodontitis, stroke, and Alzheimer’s disease linked?
MADRID –
The Spanish Society of Dentistry and Osseointegration (SEPA) and the Spanish Society of Neurology (SEN) recently released a report with the latest data on this topic. The report reviews, updates, and presents the most recent scientific evidence regarding this link. It also provides practical recommendations that, on the basis of the evidence, should be applied in dental clinics and neurology centers.
As Yago Leira, DDS, PhD, periodontist and coordinator of the SEPA-SEN working group, told this news organization, “The main takeaway from this scientific report is that patients with periodontitis are at nearly twice the risk of developing Alzheimer’s disease and at triple the risk of ischemic stroke.”
Data from the report show that individuals with periodontitis are at 2.8 times’ higher risk of ischemic stroke. The available evidence regarding hemorrhagic stroke, however, is conflicting.
How does this dental condition affect the course of cardiovascular disease? Observational studies have shown that those who have had an ischemic stroke and have a confirmed diagnosis of periodontitis are at greater risk of suffering a recurrent vascular event, worse neurologic deficit, and postictal depression than are patients without periodontitis.
Immune‐mediated inflammation
As far as its link to Alzheimer’s disease, meta-analyses of epidemiologic studies show that periodontitis is associated with a 1.7 times greater risk of this type of dementia and that the risk triples among patients with more serious forms of periodontitis.
Likewise, studies suggest that individuals with dementia or neurocognitive impairment are at a greater risk of suffering periodontitis. Other studies indicate that individuals with periodontitis have worse outcomes on various neuropsychological tests of cognitive function.
The current report presents the evidence from three clearly defined perspectives: The epidemiologic association between periodontitis and these neurologic diseases, the biological mechanisms that may explain this link, and interventional studies of dental treatment as a means of preventing stroke and Alzheimer’s disease.
“There is a possible biological explanation for these epidemiological findings. The report concludes that the low-grade chronic, systemic, immune-mediated inflammatory response induced by the bacteria and their endotoxins and the proinflammatory mediators circulating through the blood contributes to various biological processes that are involved in neurological impairment and cerebral ischemia,” said Dr. Leira, one of the report’s authors.
Ana Frank, MD, PhD, another author of this study, is head of the neurology department at the La Paz University Hospital in Madrid and a member of the SEPA-SEN group. She said in an interview that the main biological mechanism in stroke and Alzheimer’s disease is chronic exposure of the entire brain (vasculature, neurons, and astrocytes) to the harmful effects of periodontal infection. “Although low in intensity, this [exposure] is sufficient to set off a series of events that eventually lead to vascular endothelial injury, changes to neurons and astrocytes, and damage to the neuropil.”
As far as the evidence of an epidemiologic association between periodontitis and both neurologic diseases, Dr. Frank cited the exponential increase in risk brought on by periodontitis. She said that further epidemiologic studies are necessary to gain a better understanding of the magnitude of the problem.
A preventive alternative?
Dr. Leira cited evidence that periodontal treatment could provide a means of preventing stroke and dementia. He pointed out that numerous population studies have observed various oral health interventions (e.g., periodic dental prophylaxis or periodontal treatment) and regular dental visits to reduce the risk of developing dementia and stroke. “However, we don’t currently have randomized clinical trials that were designed to investigate whether periodontal treatment may be a primary or a secondary preventive measure against these neurological conditions.”
According to Dr. Leira, “There are currently several research groups in the United States and Europe, including ours, that are performing clinical trials to assess the impact of periodontal treatment on recurrent vascular events in patients with cerebrovascular disease.
“On the other hand, there are various interventional studies underway that are evaluating the potential effect of periodontal treatment on cognitive function in patients with dementia. Along these lines, there appear to be encouraging results from the 1-year follow-up in the GAIN study, which was a phase 2/3 clinical trial testing atuzaginstat. Atuzaginstat is an inhibitor of gingipain, the endotoxin produced by Porphyromonas gingivalis, which is one of the bacteria thought to be responsible for periodontitis. The drug reduces neurocognitive impairment in patients with high levels of antibodies against this periodontal pathogen.”
Toward clinical practice
The report has a practical focus. The intention is that this evidence will make its way into recommendations for dentists to implement in clinical practice, especially with elderly patients or patients with risk factors for stroke.
In this regard, Dr. Leira said, “On one hand, dentists have to know how to approach patients who have already suffered a stroke (most of whom have vascular risk factors like diabetes and hypertension), many of whom have polypharmacy and are [taking] certain drugs like blood thinners that could negatively impact various dental procedures. In such cases, it is important to maintain direct contact with a neurologist, since these patients ought to be treated with a multidisciplinary approach.
“On the other hand, each patient who comes to the dental office and has a diagnosis of periodontitis could be screened to identify potential vascular risk factors, even though the definitive diagnosis would need to be given by a specialist physician. To this end, SEPA is carrying out the Promosalud (“Health Promotion”) project, which will soon be applied in a large number of dental clinics in Spain,” added Dr. Leira.
“Lastly, specialists in odontology must understand the potential positive benefits surrounding systemic vascular inflammation that periodontal treatment could provide, including, for example, metabolic control and lowering blood pressure.”
For patients with cognitive impairment, the authors of the report recommended adhering to the following steps during dental visits: Inform the patient and the patient’s caregiver about the importance of good dental hygiene and monitor for any signs of infection or dental disease; address pain in every patient with cognitive impairment and dental problems, especially those with agitation, even if the patient isn’t specifically complaining of pain (also, try not to give opioids); finally, avoid sedation as much as possible and use the smallest effective dose if it becomes necessary.
Prescribe oral hygiene
Regarding recommendations that neurologists should follow during consultations in light of the link between these diseases and periodontitis, Dr. Frank said, “Regardless of how old our patients are, I believe it’s important to emphasize the importance of practicing good oral and dental hygiene. It’s a good strategy to put this in writing in medical reports, alongside the usual recommendations about healthy lifestyle habits and monitoring for diseases like high blood pressure, diabetes, or dyslipidemia. These, among other factors like smoking, a sedentary lifestyle, alcoholism, and other drug addictions, are vascular risk factors and are therefore risk factors for stroke and dementia.”
According to Dr. Frank, the public is largely unaware of the relationship between periodontitis and incident neurologic diseases. “We still have a long way to go before we can say that the public is aware of this potential link. And not just the public, either. I believe we must stress among our colleagues and among health care professionals in general the importance of promoting dental health to improve people’s overall health.”
In this regard, Dr. Leira emphasized the authors’ intention to make this report available not only to oral health and neurologic health care professionals but also to primary care physicians and nurses so that patients with cerebrovascular disease or Alzheimer’s disease and their caregivers can develop a greater awareness and thereby improve prevention.
“This study will also provide the scientific basis to support the SEPA-SEN working group as they implement their future activities and projects,” Dr. Leira concluded.
Dr. Leira and Dr. Frank have disclosed no relevant financial relationships.
This article was translated from the Medscape Spanish Edition. A version of this article appeared on Medscape.com.
MADRID –
The Spanish Society of Dentistry and Osseointegration (SEPA) and the Spanish Society of Neurology (SEN) recently released a report with the latest data on this topic. The report reviews, updates, and presents the most recent scientific evidence regarding this link. It also provides practical recommendations that, on the basis of the evidence, should be applied in dental clinics and neurology centers.
As Yago Leira, DDS, PhD, periodontist and coordinator of the SEPA-SEN working group, told this news organization, “The main takeaway from this scientific report is that patients with periodontitis are at nearly twice the risk of developing Alzheimer’s disease and at triple the risk of ischemic stroke.”
Data from the report show that individuals with periodontitis are at 2.8 times’ higher risk of ischemic stroke. The available evidence regarding hemorrhagic stroke, however, is conflicting.
How does this dental condition affect the course of cardiovascular disease? Observational studies have shown that those who have had an ischemic stroke and have a confirmed diagnosis of periodontitis are at greater risk of suffering a recurrent vascular event, worse neurologic deficit, and postictal depression than are patients without periodontitis.
Immune‐mediated inflammation
As far as its link to Alzheimer’s disease, meta-analyses of epidemiologic studies show that periodontitis is associated with a 1.7 times greater risk of this type of dementia and that the risk triples among patients with more serious forms of periodontitis.
Likewise, studies suggest that individuals with dementia or neurocognitive impairment are at a greater risk of suffering periodontitis. Other studies indicate that individuals with periodontitis have worse outcomes on various neuropsychological tests of cognitive function.
The current report presents the evidence from three clearly defined perspectives: The epidemiologic association between periodontitis and these neurologic diseases, the biological mechanisms that may explain this link, and interventional studies of dental treatment as a means of preventing stroke and Alzheimer’s disease.
“There is a possible biological explanation for these epidemiological findings. The report concludes that the low-grade chronic, systemic, immune-mediated inflammatory response induced by the bacteria and their endotoxins and the proinflammatory mediators circulating through the blood contributes to various biological processes that are involved in neurological impairment and cerebral ischemia,” said Dr. Leira, one of the report’s authors.
Ana Frank, MD, PhD, another author of this study, is head of the neurology department at the La Paz University Hospital in Madrid and a member of the SEPA-SEN group. She said in an interview that the main biological mechanism in stroke and Alzheimer’s disease is chronic exposure of the entire brain (vasculature, neurons, and astrocytes) to the harmful effects of periodontal infection. “Although low in intensity, this [exposure] is sufficient to set off a series of events that eventually lead to vascular endothelial injury, changes to neurons and astrocytes, and damage to the neuropil.”
As far as the evidence of an epidemiologic association between periodontitis and both neurologic diseases, Dr. Frank cited the exponential increase in risk brought on by periodontitis. She said that further epidemiologic studies are necessary to gain a better understanding of the magnitude of the problem.
A preventive alternative?
Dr. Leira cited evidence that periodontal treatment could provide a means of preventing stroke and dementia. He pointed out that numerous population studies have observed various oral health interventions (e.g., periodic dental prophylaxis or periodontal treatment) and regular dental visits to reduce the risk of developing dementia and stroke. “However, we don’t currently have randomized clinical trials that were designed to investigate whether periodontal treatment may be a primary or a secondary preventive measure against these neurological conditions.”
According to Dr. Leira, “There are currently several research groups in the United States and Europe, including ours, that are performing clinical trials to assess the impact of periodontal treatment on recurrent vascular events in patients with cerebrovascular disease.
“On the other hand, there are various interventional studies underway that are evaluating the potential effect of periodontal treatment on cognitive function in patients with dementia. Along these lines, there appear to be encouraging results from the 1-year follow-up in the GAIN study, which was a phase 2/3 clinical trial testing atuzaginstat. Atuzaginstat is an inhibitor of gingipain, the endotoxin produced by Porphyromonas gingivalis, which is one of the bacteria thought to be responsible for periodontitis. The drug reduces neurocognitive impairment in patients with high levels of antibodies against this periodontal pathogen.”
Toward clinical practice
The report has a practical focus. The intention is that this evidence will make its way into recommendations for dentists to implement in clinical practice, especially with elderly patients or patients with risk factors for stroke.
In this regard, Dr. Leira said, “On one hand, dentists have to know how to approach patients who have already suffered a stroke (most of whom have vascular risk factors like diabetes and hypertension), many of whom have polypharmacy and are [taking] certain drugs like blood thinners that could negatively impact various dental procedures. In such cases, it is important to maintain direct contact with a neurologist, since these patients ought to be treated with a multidisciplinary approach.
“On the other hand, each patient who comes to the dental office and has a diagnosis of periodontitis could be screened to identify potential vascular risk factors, even though the definitive diagnosis would need to be given by a specialist physician. To this end, SEPA is carrying out the Promosalud (“Health Promotion”) project, which will soon be applied in a large number of dental clinics in Spain,” added Dr. Leira.
“Lastly, specialists in odontology must understand the potential positive benefits surrounding systemic vascular inflammation that periodontal treatment could provide, including, for example, metabolic control and lowering blood pressure.”
For patients with cognitive impairment, the authors of the report recommended adhering to the following steps during dental visits: Inform the patient and the patient’s caregiver about the importance of good dental hygiene and monitor for any signs of infection or dental disease; address pain in every patient with cognitive impairment and dental problems, especially those with agitation, even if the patient isn’t specifically complaining of pain (also, try not to give opioids); finally, avoid sedation as much as possible and use the smallest effective dose if it becomes necessary.
Prescribe oral hygiene
Regarding recommendations that neurologists should follow during consultations in light of the link between these diseases and periodontitis, Dr. Frank said, “Regardless of how old our patients are, I believe it’s important to emphasize the importance of practicing good oral and dental hygiene. It’s a good strategy to put this in writing in medical reports, alongside the usual recommendations about healthy lifestyle habits and monitoring for diseases like high blood pressure, diabetes, or dyslipidemia. These, among other factors like smoking, a sedentary lifestyle, alcoholism, and other drug addictions, are vascular risk factors and are therefore risk factors for stroke and dementia.”
According to Dr. Frank, the public is largely unaware of the relationship between periodontitis and incident neurologic diseases. “We still have a long way to go before we can say that the public is aware of this potential link. And not just the public, either. I believe we must stress among our colleagues and among health care professionals in general the importance of promoting dental health to improve people’s overall health.”
In this regard, Dr. Leira emphasized the authors’ intention to make this report available not only to oral health and neurologic health care professionals but also to primary care physicians and nurses so that patients with cerebrovascular disease or Alzheimer’s disease and their caregivers can develop a greater awareness and thereby improve prevention.
“This study will also provide the scientific basis to support the SEPA-SEN working group as they implement their future activities and projects,” Dr. Leira concluded.
Dr. Leira and Dr. Frank have disclosed no relevant financial relationships.
This article was translated from the Medscape Spanish Edition. A version of this article appeared on Medscape.com.
MADRID –
The Spanish Society of Dentistry and Osseointegration (SEPA) and the Spanish Society of Neurology (SEN) recently released a report with the latest data on this topic. The report reviews, updates, and presents the most recent scientific evidence regarding this link. It also provides practical recommendations that, on the basis of the evidence, should be applied in dental clinics and neurology centers.
As Yago Leira, DDS, PhD, periodontist and coordinator of the SEPA-SEN working group, told this news organization, “The main takeaway from this scientific report is that patients with periodontitis are at nearly twice the risk of developing Alzheimer’s disease and at triple the risk of ischemic stroke.”
Data from the report show that individuals with periodontitis are at 2.8 times’ higher risk of ischemic stroke. The available evidence regarding hemorrhagic stroke, however, is conflicting.
How does this dental condition affect the course of cardiovascular disease? Observational studies have shown that those who have had an ischemic stroke and have a confirmed diagnosis of periodontitis are at greater risk of suffering a recurrent vascular event, worse neurologic deficit, and postictal depression than are patients without periodontitis.
Immune‐mediated inflammation
As far as its link to Alzheimer’s disease, meta-analyses of epidemiologic studies show that periodontitis is associated with a 1.7 times greater risk of this type of dementia and that the risk triples among patients with more serious forms of periodontitis.
Likewise, studies suggest that individuals with dementia or neurocognitive impairment are at a greater risk of suffering periodontitis. Other studies indicate that individuals with periodontitis have worse outcomes on various neuropsychological tests of cognitive function.
The current report presents the evidence from three clearly defined perspectives: The epidemiologic association between periodontitis and these neurologic diseases, the biological mechanisms that may explain this link, and interventional studies of dental treatment as a means of preventing stroke and Alzheimer’s disease.
“There is a possible biological explanation for these epidemiological findings. The report concludes that the low-grade chronic, systemic, immune-mediated inflammatory response induced by the bacteria and their endotoxins and the proinflammatory mediators circulating through the blood contributes to various biological processes that are involved in neurological impairment and cerebral ischemia,” said Dr. Leira, one of the report’s authors.
Ana Frank, MD, PhD, another author of this study, is head of the neurology department at the La Paz University Hospital in Madrid and a member of the SEPA-SEN group. She said in an interview that the main biological mechanism in stroke and Alzheimer’s disease is chronic exposure of the entire brain (vasculature, neurons, and astrocytes) to the harmful effects of periodontal infection. “Although low in intensity, this [exposure] is sufficient to set off a series of events that eventually lead to vascular endothelial injury, changes to neurons and astrocytes, and damage to the neuropil.”
As far as the evidence of an epidemiologic association between periodontitis and both neurologic diseases, Dr. Frank cited the exponential increase in risk brought on by periodontitis. She said that further epidemiologic studies are necessary to gain a better understanding of the magnitude of the problem.
A preventive alternative?
Dr. Leira cited evidence that periodontal treatment could provide a means of preventing stroke and dementia. He pointed out that numerous population studies have observed various oral health interventions (e.g., periodic dental prophylaxis or periodontal treatment) and regular dental visits to reduce the risk of developing dementia and stroke. “However, we don’t currently have randomized clinical trials that were designed to investigate whether periodontal treatment may be a primary or a secondary preventive measure against these neurological conditions.”
According to Dr. Leira, “There are currently several research groups in the United States and Europe, including ours, that are performing clinical trials to assess the impact of periodontal treatment on recurrent vascular events in patients with cerebrovascular disease.
“On the other hand, there are various interventional studies underway that are evaluating the potential effect of periodontal treatment on cognitive function in patients with dementia. Along these lines, there appear to be encouraging results from the 1-year follow-up in the GAIN study, which was a phase 2/3 clinical trial testing atuzaginstat. Atuzaginstat is an inhibitor of gingipain, the endotoxin produced by Porphyromonas gingivalis, which is one of the bacteria thought to be responsible for periodontitis. The drug reduces neurocognitive impairment in patients with high levels of antibodies against this periodontal pathogen.”
Toward clinical practice
The report has a practical focus. The intention is that this evidence will make its way into recommendations for dentists to implement in clinical practice, especially with elderly patients or patients with risk factors for stroke.
In this regard, Dr. Leira said, “On one hand, dentists have to know how to approach patients who have already suffered a stroke (most of whom have vascular risk factors like diabetes and hypertension), many of whom have polypharmacy and are [taking] certain drugs like blood thinners that could negatively impact various dental procedures. In such cases, it is important to maintain direct contact with a neurologist, since these patients ought to be treated with a multidisciplinary approach.
“On the other hand, each patient who comes to the dental office and has a diagnosis of periodontitis could be screened to identify potential vascular risk factors, even though the definitive diagnosis would need to be given by a specialist physician. To this end, SEPA is carrying out the Promosalud (“Health Promotion”) project, which will soon be applied in a large number of dental clinics in Spain,” added Dr. Leira.
“Lastly, specialists in odontology must understand the potential positive benefits surrounding systemic vascular inflammation that periodontal treatment could provide, including, for example, metabolic control and lowering blood pressure.”
For patients with cognitive impairment, the authors of the report recommended adhering to the following steps during dental visits: Inform the patient and the patient’s caregiver about the importance of good dental hygiene and monitor for any signs of infection or dental disease; address pain in every patient with cognitive impairment and dental problems, especially those with agitation, even if the patient isn’t specifically complaining of pain (also, try not to give opioids); finally, avoid sedation as much as possible and use the smallest effective dose if it becomes necessary.
Prescribe oral hygiene
Regarding recommendations that neurologists should follow during consultations in light of the link between these diseases and periodontitis, Dr. Frank said, “Regardless of how old our patients are, I believe it’s important to emphasize the importance of practicing good oral and dental hygiene. It’s a good strategy to put this in writing in medical reports, alongside the usual recommendations about healthy lifestyle habits and monitoring for diseases like high blood pressure, diabetes, or dyslipidemia. These, among other factors like smoking, a sedentary lifestyle, alcoholism, and other drug addictions, are vascular risk factors and are therefore risk factors for stroke and dementia.”
According to Dr. Frank, the public is largely unaware of the relationship between periodontitis and incident neurologic diseases. “We still have a long way to go before we can say that the public is aware of this potential link. And not just the public, either. I believe we must stress among our colleagues and among health care professionals in general the importance of promoting dental health to improve people’s overall health.”
In this regard, Dr. Leira emphasized the authors’ intention to make this report available not only to oral health and neurologic health care professionals but also to primary care physicians and nurses so that patients with cerebrovascular disease or Alzheimer’s disease and their caregivers can develop a greater awareness and thereby improve prevention.
“This study will also provide the scientific basis to support the SEPA-SEN working group as they implement their future activities and projects,” Dr. Leira concluded.
Dr. Leira and Dr. Frank have disclosed no relevant financial relationships.
This article was translated from the Medscape Spanish Edition. A version of this article appeared on Medscape.com.
Ticagrelor may reduce brain lesions after carotid stenting
MUNICH – secondary endpoint results of the PRECISE-MRI trial suggest.
More than 200 patients with carotid artery stenosis underwent MRI and were randomized to ticagrelor or clopidogrel before undergoing CAS. They then had two follow-up MRIs to assess the presence of emergent ischemic lesions.
Although the trial, which was stopped early, failed to show a difference between the two treatments in the primary endpoint – occurrence of at least one ischemic lesion – it did show that ticagrelor was associated with significant reductions in secondary endpoints including the total number and total volume of new lesions.
There were also significantly fewer cases of a composite of adverse clinical events with ticagrelor versus clopidogrel, but no difference in rates of hemorrhagic bleeds.
The research was presented at the annual European Stroke Organisation Conference .
Highlighting the failure of the trial to meet its primary endpoint, study presenter Leo Bonati, MD, head of the Stroke Center, Rena Rheinfelden, University Hospital Basel (Switzerland), pointed out that the proportion of patients with one or more ischemic brain lesions was “much higher than expected.”
Based on the secondary outcomes, the study nevertheless indicates that, “compared with clopidogrel, ticagrelor reduces the total burden of ischemic brain lesions occurring during CAS,” he said.
Ticagrelor is therefore a “safe alternative to clopidogrel as an add-on to aspirin to cover carotid artery stent procedures.”
Dr. Bonati cautioned, however, that the findings are preliminary.
‘Promising’ results
Session cochair Else Charlotte Sandset, MD, PhD, a consultant neurologist in the stroke unit, department of neurology, Oslo University Hospital, called the results “interesting” and “promising.”
She said in an interview that they “also provide us with an additional option” in the management of patients undergoing CAS.
Dr. Sandset suggested that “it may have been a little bit hard to prove the primary endpoint” chosen for the trial, but believes that the secondary endpoint results “are very interesting.”
“Of course, we would need more data and further trials to provide some reassurance that we can use ticagrelor in this fashion,” she said.
Major complication
Dr. Bonati began by noting that the major procedural complication of CAS is embolic stroke, but this may be prevented with optimized antiplatelet therapy.
Previous studies have shown that ticagrelor is superior to clopidogrel as an add-on to aspirin in reducing rates of major adverse cardiovascular events in acute coronary syndrome patients undergoing percutaneous coronary intervention.
Adding the drug to aspirin is also superior to aspirin alone in preventing recurrent stroke in patients with minor stroke or transient ischemic attack, Dr. Bonati said.
To examine whether ticagrelor is superior to clopidogrel as an add-on to aspirin in preventing ischemic brain lesions during CAS, the team conducted a randomized, open, active-controlled trial.
They recruited patients with ≥ 50% symptomatic or asymptomatic carotid stenosis undergoing CAS in line with local guidelines and performed a baseline MRI scan and clinical examination.
The patients were then randomized to ticagrelor or clopidogrel plus aspirin 1-3 days before undergoing CAS. A second MRI and clinical examination, as well as an ultrasound scan, was performed at 1 to 3 days post-CAS, with a third set of examinations performed at 28-32 days after the procedure.
The study included 14 sites in Belgium, Germany, Italy, the Netherlands, Switzerland, and the United Kingdom. Enrollment was stopped after 209 of the originally planned 370 patients, “due to slow recruitment and a lack of further funding,” Dr. Bonati said.
Of those, 207 patients were included in the intention-to-treat safety analysis, and 172 in the per-protocol efficacy analysis.
The mean age of the patients was 69.0-69.5 years in the two treatment groups, and 67%-71% were male. Dr. Bonati noted that 52%-55% of the patients had symptomatic stenosis, and that in 83%-88% the stenosis was severe.
The majority (79%-82%) of patients had hypertension, alongside hypercholesterolemia, at 76% in both treatment groups.
Dr. Bonati showed that there was no significant difference in the primary efficacy outcome of the presence of at least new ischemic brain lesion on the second or third MRI, at 74.7% for patients given ticagrelor versus 79.8% with clopidogrel, or a relative risk of 0.94 (95% confidence interval, 0.79-1.10; P = .43).
However, there was a significant reduction in the number of new ischemic lesions, at a median of 2 (interquartile range, 0.5-5.5) with ticagrelor versus 3 with clopidogrel (IQR, 1-8), or an exponential beta value of 0.63 (95% CI, 0.42-0.95; P = .027).
Ticagrelor was also associated with a significant reduction in the total volume of lesions, at a median of 66 mcL (IQR, 2.5-2.19) versus 91 mcL (IQR, 25-394) for clopidogrel, or an exponential beta value of 0.30 (95% CI, 0.10-0.92; P = .030).
Patients assigned to ticagrelor also had a significantly lower rate of the primary clinical safety outcome, a composite of stroke, myocardial infarction, major bleeding, or cardiovascular death, at 2.9% versus 7.8% (relative risk, 0.36; 95% CI, 0.08-1.20). This was driven by a reduction in rates of post-CAS stroke.
Dr. Bonati noted that there was no significant difference in the presence of at least one hemorrhagic lesion after CAS, at 42.7% with ticagrelor and 47.6% in the clopidogrel group (RR, 0.90; 95% CI, 0.63-1.26).
There was also a similar rate of microbleeds between the two treatment groups, at 36.6% in patients given ticagrelor and 47.6% in those assigned to clopidogrel.
The study was investigator initiated and funded by an unrestricted research grant from AstraZeneca. No relevant financial relationships were declared.
A version of this article first appeared on Medscape.com.
MUNICH – secondary endpoint results of the PRECISE-MRI trial suggest.
More than 200 patients with carotid artery stenosis underwent MRI and were randomized to ticagrelor or clopidogrel before undergoing CAS. They then had two follow-up MRIs to assess the presence of emergent ischemic lesions.
Although the trial, which was stopped early, failed to show a difference between the two treatments in the primary endpoint – occurrence of at least one ischemic lesion – it did show that ticagrelor was associated with significant reductions in secondary endpoints including the total number and total volume of new lesions.
There were also significantly fewer cases of a composite of adverse clinical events with ticagrelor versus clopidogrel, but no difference in rates of hemorrhagic bleeds.
The research was presented at the annual European Stroke Organisation Conference .
Highlighting the failure of the trial to meet its primary endpoint, study presenter Leo Bonati, MD, head of the Stroke Center, Rena Rheinfelden, University Hospital Basel (Switzerland), pointed out that the proportion of patients with one or more ischemic brain lesions was “much higher than expected.”
Based on the secondary outcomes, the study nevertheless indicates that, “compared with clopidogrel, ticagrelor reduces the total burden of ischemic brain lesions occurring during CAS,” he said.
Ticagrelor is therefore a “safe alternative to clopidogrel as an add-on to aspirin to cover carotid artery stent procedures.”
Dr. Bonati cautioned, however, that the findings are preliminary.
‘Promising’ results
Session cochair Else Charlotte Sandset, MD, PhD, a consultant neurologist in the stroke unit, department of neurology, Oslo University Hospital, called the results “interesting” and “promising.”
She said in an interview that they “also provide us with an additional option” in the management of patients undergoing CAS.
Dr. Sandset suggested that “it may have been a little bit hard to prove the primary endpoint” chosen for the trial, but believes that the secondary endpoint results “are very interesting.”
“Of course, we would need more data and further trials to provide some reassurance that we can use ticagrelor in this fashion,” she said.
Major complication
Dr. Bonati began by noting that the major procedural complication of CAS is embolic stroke, but this may be prevented with optimized antiplatelet therapy.
Previous studies have shown that ticagrelor is superior to clopidogrel as an add-on to aspirin in reducing rates of major adverse cardiovascular events in acute coronary syndrome patients undergoing percutaneous coronary intervention.
Adding the drug to aspirin is also superior to aspirin alone in preventing recurrent stroke in patients with minor stroke or transient ischemic attack, Dr. Bonati said.
To examine whether ticagrelor is superior to clopidogrel as an add-on to aspirin in preventing ischemic brain lesions during CAS, the team conducted a randomized, open, active-controlled trial.
They recruited patients with ≥ 50% symptomatic or asymptomatic carotid stenosis undergoing CAS in line with local guidelines and performed a baseline MRI scan and clinical examination.
The patients were then randomized to ticagrelor or clopidogrel plus aspirin 1-3 days before undergoing CAS. A second MRI and clinical examination, as well as an ultrasound scan, was performed at 1 to 3 days post-CAS, with a third set of examinations performed at 28-32 days after the procedure.
The study included 14 sites in Belgium, Germany, Italy, the Netherlands, Switzerland, and the United Kingdom. Enrollment was stopped after 209 of the originally planned 370 patients, “due to slow recruitment and a lack of further funding,” Dr. Bonati said.
Of those, 207 patients were included in the intention-to-treat safety analysis, and 172 in the per-protocol efficacy analysis.
The mean age of the patients was 69.0-69.5 years in the two treatment groups, and 67%-71% were male. Dr. Bonati noted that 52%-55% of the patients had symptomatic stenosis, and that in 83%-88% the stenosis was severe.
The majority (79%-82%) of patients had hypertension, alongside hypercholesterolemia, at 76% in both treatment groups.
Dr. Bonati showed that there was no significant difference in the primary efficacy outcome of the presence of at least new ischemic brain lesion on the second or third MRI, at 74.7% for patients given ticagrelor versus 79.8% with clopidogrel, or a relative risk of 0.94 (95% confidence interval, 0.79-1.10; P = .43).
However, there was a significant reduction in the number of new ischemic lesions, at a median of 2 (interquartile range, 0.5-5.5) with ticagrelor versus 3 with clopidogrel (IQR, 1-8), or an exponential beta value of 0.63 (95% CI, 0.42-0.95; P = .027).
Ticagrelor was also associated with a significant reduction in the total volume of lesions, at a median of 66 mcL (IQR, 2.5-2.19) versus 91 mcL (IQR, 25-394) for clopidogrel, or an exponential beta value of 0.30 (95% CI, 0.10-0.92; P = .030).
Patients assigned to ticagrelor also had a significantly lower rate of the primary clinical safety outcome, a composite of stroke, myocardial infarction, major bleeding, or cardiovascular death, at 2.9% versus 7.8% (relative risk, 0.36; 95% CI, 0.08-1.20). This was driven by a reduction in rates of post-CAS stroke.
Dr. Bonati noted that there was no significant difference in the presence of at least one hemorrhagic lesion after CAS, at 42.7% with ticagrelor and 47.6% in the clopidogrel group (RR, 0.90; 95% CI, 0.63-1.26).
There was also a similar rate of microbleeds between the two treatment groups, at 36.6% in patients given ticagrelor and 47.6% in those assigned to clopidogrel.
The study was investigator initiated and funded by an unrestricted research grant from AstraZeneca. No relevant financial relationships were declared.
A version of this article first appeared on Medscape.com.
MUNICH – secondary endpoint results of the PRECISE-MRI trial suggest.
More than 200 patients with carotid artery stenosis underwent MRI and were randomized to ticagrelor or clopidogrel before undergoing CAS. They then had two follow-up MRIs to assess the presence of emergent ischemic lesions.
Although the trial, which was stopped early, failed to show a difference between the two treatments in the primary endpoint – occurrence of at least one ischemic lesion – it did show that ticagrelor was associated with significant reductions in secondary endpoints including the total number and total volume of new lesions.
There were also significantly fewer cases of a composite of adverse clinical events with ticagrelor versus clopidogrel, but no difference in rates of hemorrhagic bleeds.
The research was presented at the annual European Stroke Organisation Conference .
Highlighting the failure of the trial to meet its primary endpoint, study presenter Leo Bonati, MD, head of the Stroke Center, Rena Rheinfelden, University Hospital Basel (Switzerland), pointed out that the proportion of patients with one or more ischemic brain lesions was “much higher than expected.”
Based on the secondary outcomes, the study nevertheless indicates that, “compared with clopidogrel, ticagrelor reduces the total burden of ischemic brain lesions occurring during CAS,” he said.
Ticagrelor is therefore a “safe alternative to clopidogrel as an add-on to aspirin to cover carotid artery stent procedures.”
Dr. Bonati cautioned, however, that the findings are preliminary.
‘Promising’ results
Session cochair Else Charlotte Sandset, MD, PhD, a consultant neurologist in the stroke unit, department of neurology, Oslo University Hospital, called the results “interesting” and “promising.”
She said in an interview that they “also provide us with an additional option” in the management of patients undergoing CAS.
Dr. Sandset suggested that “it may have been a little bit hard to prove the primary endpoint” chosen for the trial, but believes that the secondary endpoint results “are very interesting.”
“Of course, we would need more data and further trials to provide some reassurance that we can use ticagrelor in this fashion,” she said.
Major complication
Dr. Bonati began by noting that the major procedural complication of CAS is embolic stroke, but this may be prevented with optimized antiplatelet therapy.
Previous studies have shown that ticagrelor is superior to clopidogrel as an add-on to aspirin in reducing rates of major adverse cardiovascular events in acute coronary syndrome patients undergoing percutaneous coronary intervention.
Adding the drug to aspirin is also superior to aspirin alone in preventing recurrent stroke in patients with minor stroke or transient ischemic attack, Dr. Bonati said.
To examine whether ticagrelor is superior to clopidogrel as an add-on to aspirin in preventing ischemic brain lesions during CAS, the team conducted a randomized, open, active-controlled trial.
They recruited patients with ≥ 50% symptomatic or asymptomatic carotid stenosis undergoing CAS in line with local guidelines and performed a baseline MRI scan and clinical examination.
The patients were then randomized to ticagrelor or clopidogrel plus aspirin 1-3 days before undergoing CAS. A second MRI and clinical examination, as well as an ultrasound scan, was performed at 1 to 3 days post-CAS, with a third set of examinations performed at 28-32 days after the procedure.
The study included 14 sites in Belgium, Germany, Italy, the Netherlands, Switzerland, and the United Kingdom. Enrollment was stopped after 209 of the originally planned 370 patients, “due to slow recruitment and a lack of further funding,” Dr. Bonati said.
Of those, 207 patients were included in the intention-to-treat safety analysis, and 172 in the per-protocol efficacy analysis.
The mean age of the patients was 69.0-69.5 years in the two treatment groups, and 67%-71% were male. Dr. Bonati noted that 52%-55% of the patients had symptomatic stenosis, and that in 83%-88% the stenosis was severe.
The majority (79%-82%) of patients had hypertension, alongside hypercholesterolemia, at 76% in both treatment groups.
Dr. Bonati showed that there was no significant difference in the primary efficacy outcome of the presence of at least new ischemic brain lesion on the second or third MRI, at 74.7% for patients given ticagrelor versus 79.8% with clopidogrel, or a relative risk of 0.94 (95% confidence interval, 0.79-1.10; P = .43).
However, there was a significant reduction in the number of new ischemic lesions, at a median of 2 (interquartile range, 0.5-5.5) with ticagrelor versus 3 with clopidogrel (IQR, 1-8), or an exponential beta value of 0.63 (95% CI, 0.42-0.95; P = .027).
Ticagrelor was also associated with a significant reduction in the total volume of lesions, at a median of 66 mcL (IQR, 2.5-2.19) versus 91 mcL (IQR, 25-394) for clopidogrel, or an exponential beta value of 0.30 (95% CI, 0.10-0.92; P = .030).
Patients assigned to ticagrelor also had a significantly lower rate of the primary clinical safety outcome, a composite of stroke, myocardial infarction, major bleeding, or cardiovascular death, at 2.9% versus 7.8% (relative risk, 0.36; 95% CI, 0.08-1.20). This was driven by a reduction in rates of post-CAS stroke.
Dr. Bonati noted that there was no significant difference in the presence of at least one hemorrhagic lesion after CAS, at 42.7% with ticagrelor and 47.6% in the clopidogrel group (RR, 0.90; 95% CI, 0.63-1.26).
There was also a similar rate of microbleeds between the two treatment groups, at 36.6% in patients given ticagrelor and 47.6% in those assigned to clopidogrel.
The study was investigator initiated and funded by an unrestricted research grant from AstraZeneca. No relevant financial relationships were declared.
A version of this article first appeared on Medscape.com.
FROM ESOC 2023