Stroke

TOPLINE: 

Among patients hospitalized with a first ischemic stroke, 80% were rehospitalized, primarily because of subsequent primary cardiovascular and cerebrovascular diagnoses.

METHODOLOGY:

• To gather information on post-stroke hospital admission, investigators followed 1412 participants (mean age, 72.4 years; 52.1% women, 35.3% Black individuals) from the Atherosclerosis Risk in Communities (ARIC) study who were living in Maryland, Minnesota, North Carolina, and Mississippi.
• Participants were recruited between 1987 and 1989 when they were 45-64 years old and were followed on an annual and then semiannual basis from the index discharge until discharge after their second hospitalization, death, or end of the study in December 2019.
• Specific diagnoses for each hospitalization were based on hospital records, discharge diagnoses, and annual and semiannual phone interviews.

TAKEAWAY: 

• During the study period, 1143 hospitalizations occurred over 41,849 person-months.
• 81% of participants were hospitalized over a maximum of 26.6 years of follow-up. Primary cardiovascular and cerebrovascular diagnoses were reported for half of readmissions.
• Over the follow-up period, compared with cardioembolic stroke, readmission risk was lower for thrombotic/lacunar stroke (adjusted hazard ratio [aHR], 0.82; 95% CI, 0.71-0.95) and hemorrhagic stroke (aHR, 0.74; 95% CI, 0.58-0.93). However, when adjusting for atrial fibrillation and competing risk for death, there were no significant differences between stroke subtypes.
• Compared with cardioembolic stroke, thrombotic/lacunar stroke was associated with lower readmission risk within 1 month (aHR, 0.66; 95% CI, 0.46-0.93) and from 1 month to 1 year (aHR, 0.78; 95% CI, 0.62-0.97), and hemorrhagic stroke was associated with lower risk from 1 month to 1 year (aHR, 0.60; 95% CI, 0.41-0.87).

IN PRACTICE:

“These results suggest that prevention strategies focused on cardiovascular and cerebrovascular health warrant further investigation, especially within the first year after incident stroke and perhaps particularly among individuals with an incident cardioembolic stroke,” the authors wrote.

SOURCE:

Kelly Sloane, MD, of the University of Pennsylvania Perelman School of Medicine in Philadelphia, led the study along with colleagues at the National Institute of Neurological Disorders and Stroke, Johns Hopkins University in Baltimore, and the University of North Carolina, Chapel Hill. The article was published online on January 5 in Neurology.

LIMITATIONS:

The ARIC study classification of stroke subtype grouped embolic strokes of undetermined source as thrombotic strokes, and investigators were unable to distinguish between the groups. In addition, there was no way to measure stroke severity, which could have played a role in readmission risk.

DISCLOSURES:

The study was funded by the National Heart, Lung, and Blood Institute, the National Institute of Neurological Disorders and Stroke, and the National Institutes of Health.

A version of this article appeared on Medscape.com.

TOPLINE: 

Among patients hospitalized with a first ischemic stroke, 80% were rehospitalized, primarily because of subsequent primary cardiovascular and cerebrovascular diagnoses.

METHODOLOGY:

• To gather information on post-stroke hospital admission, investigators followed 1412 participants (mean age, 72.4 years; 52.1% women, 35.3% Black individuals) from the Atherosclerosis Risk in Communities (ARIC) study who were living in Maryland, Minnesota, North Carolina, and Mississippi.
• Participants were recruited between 1987 and 1989 when they were 45-64 years old and were followed on an annual and then semiannual basis from the index discharge until discharge after their second hospitalization, death, or end of the study in December 2019.
• Specific diagnoses for each hospitalization were based on hospital records, discharge diagnoses, and annual and semiannual phone interviews.

TAKEAWAY: 

• During the study period, 1143 hospitalizations occurred over 41,849 person-months.
• 81% of participants were hospitalized over a maximum of 26.6 years of follow-up. Primary cardiovascular and cerebrovascular diagnoses were reported for half of readmissions.
• Over the follow-up period, compared with cardioembolic stroke, readmission risk was lower for thrombotic/lacunar stroke (adjusted hazard ratio [aHR], 0.82; 95% CI, 0.71-0.95) and hemorrhagic stroke (aHR, 0.74; 95% CI, 0.58-0.93). However, when adjusting for atrial fibrillation and competing risk for death, there were no significant differences between stroke subtypes.
• Compared with cardioembolic stroke, thrombotic/lacunar stroke was associated with lower readmission risk within 1 month (aHR, 0.66; 95% CI, 0.46-0.93) and from 1 month to 1 year (aHR, 0.78; 95% CI, 0.62-0.97), and hemorrhagic stroke was associated with lower risk from 1 month to 1 year (aHR, 0.60; 95% CI, 0.41-0.87).

IN PRACTICE:

“These results suggest that prevention strategies focused on cardiovascular and cerebrovascular health warrant further investigation, especially within the first year after incident stroke and perhaps particularly among individuals with an incident cardioembolic stroke,” the authors wrote.

SOURCE:

Kelly Sloane, MD, of the University of Pennsylvania Perelman School of Medicine in Philadelphia, led the study along with colleagues at the National Institute of Neurological Disorders and Stroke, Johns Hopkins University in Baltimore, and the University of North Carolina, Chapel Hill. The article was published online on January 5 in Neurology.

LIMITATIONS:

The ARIC study classification of stroke subtype grouped embolic strokes of undetermined source as thrombotic strokes, and investigators were unable to distinguish between the groups. In addition, there was no way to measure stroke severity, which could have played a role in readmission risk.

DISCLOSURES:

The study was funded by the National Heart, Lung, and Blood Institute, the National Institute of Neurological Disorders and Stroke, and the National Institutes of Health.

A version of this article appeared on Medscape.com.

TOPLINE: 

Among patients hospitalized with a first ischemic stroke, 80% were rehospitalized, primarily because of subsequent primary cardiovascular and cerebrovascular diagnoses.

METHODOLOGY:

• To gather information on post-stroke hospital admission, investigators followed 1412 participants (mean age, 72.4 years; 52.1% women, 35.3% Black individuals) from the Atherosclerosis Risk in Communities (ARIC) study who were living in Maryland, Minnesota, North Carolina, and Mississippi.
• Participants were recruited between 1987 and 1989 when they were 45-64 years old and were followed on an annual and then semiannual basis from the index discharge until discharge after their second hospitalization, death, or end of the study in December 2019.
• Specific diagnoses for each hospitalization were based on hospital records, discharge diagnoses, and annual and semiannual phone interviews.

TAKEAWAY: 

• During the study period, 1143 hospitalizations occurred over 41,849 person-months.
• 81% of participants were hospitalized over a maximum of 26.6 years of follow-up. Primary cardiovascular and cerebrovascular diagnoses were reported for half of readmissions.
• Over the follow-up period, compared with cardioembolic stroke, readmission risk was lower for thrombotic/lacunar stroke (adjusted hazard ratio [aHR], 0.82; 95% CI, 0.71-0.95) and hemorrhagic stroke (aHR, 0.74; 95% CI, 0.58-0.93). However, when adjusting for atrial fibrillation and competing risk for death, there were no significant differences between stroke subtypes.
• Compared with cardioembolic stroke, thrombotic/lacunar stroke was associated with lower readmission risk within 1 month (aHR, 0.66; 95% CI, 0.46-0.93) and from 1 month to 1 year (aHR, 0.78; 95% CI, 0.62-0.97), and hemorrhagic stroke was associated with lower risk from 1 month to 1 year (aHR, 0.60; 95% CI, 0.41-0.87).

IN PRACTICE:

“These results suggest that prevention strategies focused on cardiovascular and cerebrovascular health warrant further investigation, especially within the first year after incident stroke and perhaps particularly among individuals with an incident cardioembolic stroke,” the authors wrote.

SOURCE:

Kelly Sloane, MD, of the University of Pennsylvania Perelman School of Medicine in Philadelphia, led the study along with colleagues at the National Institute of Neurological Disorders and Stroke, Johns Hopkins University in Baltimore, and the University of North Carolina, Chapel Hill. The article was published online on January 5 in Neurology.

LIMITATIONS:

The ARIC study classification of stroke subtype grouped embolic strokes of undetermined source as thrombotic strokes, and investigators were unable to distinguish between the groups. In addition, there was no way to measure stroke severity, which could have played a role in readmission risk.

DISCLOSURES:

The study was funded by the National Heart, Lung, and Blood Institute, the National Institute of Neurological Disorders and Stroke, and the National Institutes of Health.

A version of this article appeared on Medscape.com.

TOPLINE:

Patients undergoing transcatheter aortic valve replacement (TAVR) have a higher risk for stroke for up to 2 years compared with an age- and sex-matched population, after which their risks are comparable, results of a large Swiss registry study suggest.

METHODOLOGY:

• The study included 11,957 patients from the prospective SwissTAVI Registry, an ongoing mandatory cohort study enrolling consecutive patients undergoing TAVR in Switzerland.
• The study population, which had a mean age of 81.8 years and mean Society of Thoracic Surgeons Predicted Risk of Mortality (STS PROM) of 4.62, with 11.8% having a history of cerebrovascular accident (CVA) and 32.3% a history of atrial fibrillation, underwent TAVR at 15 centers between February 2011 and June 2021.
• The primary outcome was the incidence of stroke, with secondary outcomes including the incidence of CVA, a composite of stroke and transient ischemic attack (TIA).
• Researchers calculated standardized stroke ratios (SSRs) and compared stroke trends in patients undergoing TAVR with those of an age- and sex-matched general population in Switzerland derived from the 2019 Global Burden of Disease (GBD) study.

TAKEAWAY:

• The 30-day incidence rates of CVA and stroke were 3.3% and 3.0%, respectively, with the highest risk within the first 48 hours post TAVR, accounting for 69% of these events.
• After excluding 30-day events, the 1-year incidence rates of CVA and stroke were 1.7% and 1.4%, respectively, followed by an annual stroke incidence of 1.2%, 0.8%, 0.9%, and 0.7% in the second, third, fourth, and fifth years post TAVR, respectively.
• Only increased age and moderate/severe paravalvular leakage (PVL) at discharge were associated with an increased risk for early stroke (up to 30 days post TAVR), whereas dyslipidemia and history of atrial fibrillation and of CVA were associated with an increased risk for late stroke (30 days to 5 years after TAVR).
• SSR in the study population returned to a level comparable to that expected in the general Swiss population after 2 years and through to 5 years post-TAVR.

IN PRACTICE:

Although the study results “are reassuring” with respect to stroke risk beyond 2 years post TAVR, “our findings underscore the continued efforts of stroke-prevention measures” early and longer term, wrote the authors.

In an accompanying editorial, Lauge Østergaard, MD, PhD, Department of Cardiology, University of Copenhagen, Denmark, noted the study suggests reduced PVL could lower the risk for early stroke following TAVR and “highlights how assessment of usual risk factors (dyslipidemia and atrial fibrillation) could help reduce the burden of stroke in the long term.”

SOURCE:

The study was carried out by Taishi Okuno, MD, Department of Cardiology, Bern University Hospital, University of Bern, Switzerland, and colleagues. It was published online in the Journal of the American College of Cardiology (JACC): Cardiovascular Interventions.

LIMITATIONS:

The study couldn’t investigate the association between antithrombotic regimens and the risk for CVA. Definitions of CVA in the SwissTAVI Registry might differ from those used in the GBD study from which the matched population data were derived. The general population wasn’t matched on comorbidities usually associated with elevated stroke risk, which may have led to underestimation of stroke. As the mean age in the study was 82 years, results may not be extrapolated to a younger population.

DISCLOSURES:

The SwissTAVI registry is supported by the Swiss Heart Foundation, Swiss Working Group of Interventional Cardiology and Acute Coronary Syndromes, Medtronic, Edwards Lifesciences, Boston Scientific/Symetis, JenaValve, and St. Jude Medical. Dr. Okuno has no relevant conflicts of interest; see paper for disclosures of other study authors. Dr. Østergaard has received an independent research grant from the Novo Nordisk Foundation.

A version of this article appeared on Medscape.com.

TOPLINE:

Patients undergoing transcatheter aortic valve replacement (TAVR) have a higher risk for stroke for up to 2 years compared with an age- and sex-matched population, after which their risks are comparable, results of a large Swiss registry study suggest.

METHODOLOGY:

• The study included 11,957 patients from the prospective SwissTAVI Registry, an ongoing mandatory cohort study enrolling consecutive patients undergoing TAVR in Switzerland.
• The study population, which had a mean age of 81.8 years and mean Society of Thoracic Surgeons Predicted Risk of Mortality (STS PROM) of 4.62, with 11.8% having a history of cerebrovascular accident (CVA) and 32.3% a history of atrial fibrillation, underwent TAVR at 15 centers between February 2011 and June 2021.
• The primary outcome was the incidence of stroke, with secondary outcomes including the incidence of CVA, a composite of stroke and transient ischemic attack (TIA).
• Researchers calculated standardized stroke ratios (SSRs) and compared stroke trends in patients undergoing TAVR with those of an age- and sex-matched general population in Switzerland derived from the 2019 Global Burden of Disease (GBD) study.

TAKEAWAY:

• The 30-day incidence rates of CVA and stroke were 3.3% and 3.0%, respectively, with the highest risk within the first 48 hours post TAVR, accounting for 69% of these events.
• After excluding 30-day events, the 1-year incidence rates of CVA and stroke were 1.7% and 1.4%, respectively, followed by an annual stroke incidence of 1.2%, 0.8%, 0.9%, and 0.7% in the second, third, fourth, and fifth years post TAVR, respectively.
• Only increased age and moderate/severe paravalvular leakage (PVL) at discharge were associated with an increased risk for early stroke (up to 30 days post TAVR), whereas dyslipidemia and history of atrial fibrillation and of CVA were associated with an increased risk for late stroke (30 days to 5 years after TAVR).
• SSR in the study population returned to a level comparable to that expected in the general Swiss population after 2 years and through to 5 years post-TAVR.

IN PRACTICE:

Although the study results “are reassuring” with respect to stroke risk beyond 2 years post TAVR, “our findings underscore the continued efforts of stroke-prevention measures” early and longer term, wrote the authors.

In an accompanying editorial, Lauge Østergaard, MD, PhD, Department of Cardiology, University of Copenhagen, Denmark, noted the study suggests reduced PVL could lower the risk for early stroke following TAVR and “highlights how assessment of usual risk factors (dyslipidemia and atrial fibrillation) could help reduce the burden of stroke in the long term.”

SOURCE:

The study was carried out by Taishi Okuno, MD, Department of Cardiology, Bern University Hospital, University of Bern, Switzerland, and colleagues. It was published online in the Journal of the American College of Cardiology (JACC): Cardiovascular Interventions.

LIMITATIONS:

The study couldn’t investigate the association between antithrombotic regimens and the risk for CVA. Definitions of CVA in the SwissTAVI Registry might differ from those used in the GBD study from which the matched population data were derived. The general population wasn’t matched on comorbidities usually associated with elevated stroke risk, which may have led to underestimation of stroke. As the mean age in the study was 82 years, results may not be extrapolated to a younger population.

DISCLOSURES:

The SwissTAVI registry is supported by the Swiss Heart Foundation, Swiss Working Group of Interventional Cardiology and Acute Coronary Syndromes, Medtronic, Edwards Lifesciences, Boston Scientific/Symetis, JenaValve, and St. Jude Medical. Dr. Okuno has no relevant conflicts of interest; see paper for disclosures of other study authors. Dr. Østergaard has received an independent research grant from the Novo Nordisk Foundation.

A version of this article appeared on Medscape.com.

TOPLINE:

Patients undergoing transcatheter aortic valve replacement (TAVR) have a higher risk for stroke for up to 2 years compared with an age- and sex-matched population, after which their risks are comparable, results of a large Swiss registry study suggest.

METHODOLOGY:

• The study included 11,957 patients from the prospective SwissTAVI Registry, an ongoing mandatory cohort study enrolling consecutive patients undergoing TAVR in Switzerland.
• The study population, which had a mean age of 81.8 years and mean Society of Thoracic Surgeons Predicted Risk of Mortality (STS PROM) of 4.62, with 11.8% having a history of cerebrovascular accident (CVA) and 32.3% a history of atrial fibrillation, underwent TAVR at 15 centers between February 2011 and June 2021.
• The primary outcome was the incidence of stroke, with secondary outcomes including the incidence of CVA, a composite of stroke and transient ischemic attack (TIA).
• Researchers calculated standardized stroke ratios (SSRs) and compared stroke trends in patients undergoing TAVR with those of an age- and sex-matched general population in Switzerland derived from the 2019 Global Burden of Disease (GBD) study.

TAKEAWAY:

• The 30-day incidence rates of CVA and stroke were 3.3% and 3.0%, respectively, with the highest risk within the first 48 hours post TAVR, accounting for 69% of these events.
• After excluding 30-day events, the 1-year incidence rates of CVA and stroke were 1.7% and 1.4%, respectively, followed by an annual stroke incidence of 1.2%, 0.8%, 0.9%, and 0.7% in the second, third, fourth, and fifth years post TAVR, respectively.
• Only increased age and moderate/severe paravalvular leakage (PVL) at discharge were associated with an increased risk for early stroke (up to 30 days post TAVR), whereas dyslipidemia and history of atrial fibrillation and of CVA were associated with an increased risk for late stroke (30 days to 5 years after TAVR).
• SSR in the study population returned to a level comparable to that expected in the general Swiss population after 2 years and through to 5 years post-TAVR.

IN PRACTICE:

Although the study results “are reassuring” with respect to stroke risk beyond 2 years post TAVR, “our findings underscore the continued efforts of stroke-prevention measures” early and longer term, wrote the authors.

In an accompanying editorial, Lauge Østergaard, MD, PhD, Department of Cardiology, University of Copenhagen, Denmark, noted the study suggests reduced PVL could lower the risk for early stroke following TAVR and “highlights how assessment of usual risk factors (dyslipidemia and atrial fibrillation) could help reduce the burden of stroke in the long term.”

SOURCE:

The study was carried out by Taishi Okuno, MD, Department of Cardiology, Bern University Hospital, University of Bern, Switzerland, and colleagues. It was published online in the Journal of the American College of Cardiology (JACC): Cardiovascular Interventions.

LIMITATIONS:

The study couldn’t investigate the association between antithrombotic regimens and the risk for CVA. Definitions of CVA in the SwissTAVI Registry might differ from those used in the GBD study from which the matched population data were derived. The general population wasn’t matched on comorbidities usually associated with elevated stroke risk, which may have led to underestimation of stroke. As the mean age in the study was 82 years, results may not be extrapolated to a younger population.

DISCLOSURES:

The SwissTAVI registry is supported by the Swiss Heart Foundation, Swiss Working Group of Interventional Cardiology and Acute Coronary Syndromes, Medtronic, Edwards Lifesciences, Boston Scientific/Symetis, JenaValve, and St. Jude Medical. Dr. Okuno has no relevant conflicts of interest; see paper for disclosures of other study authors. Dr. Østergaard has received an independent research grant from the Novo Nordisk Foundation.

A version of this article appeared on Medscape.com.

ORLANDO — Combining an enzyme-inducing antiseizure medication with a direct-acting oral anticoagulant (DOAC) does not significantly increase the risk of thromboembolic events in patients with epilepsy, preliminary results of a new study show.

These new data are important, “particularly when we’re talking about a more global perspective, given the vital role of enzyme-inducing antiseizure medications in epilepsy care across many middle- and low-income countries where they may be the only readily available treatment options,” said study investigator Emily K. Acton, PhD candidate in epidemiology and a medical student, University of Pennsylvania Perelman School of Medicine, Philadelphia, and University of Illinois College of Medicine, Chicago. 

The findings also suggest that use of enzyme-inducing antiseizure medication with DOACs may be associated with a reduction in major bleeding events, although Ms. Acton stressed this requires more research.

The findings were presented at the American Epilepsy Society annual meeting.
 

Important Implications

Enzyme-inducing antiseizure medications may induce key drug metabolizing enzymes that result in wide-ranging interactions, Ms. Acton told this news organization. “But, in many cases, the clinical significance of these pharmacokinetic interactions is not completely understood.”

This has important implications for managing anticoagulation, said Ms. Acton. “The ease of DOAC use, and growing evidence of the drugs’ safety and efficacy compared to vitamin K antagonists, has led to widespread shifts in clinical practice towards DOACs.”

Due to the relative novelty of DOACs, their interaction profiles have been less than complete, she explained. Evidence that enzyme-inducing antiseizure medications may reduce absorption and accelerate metabolism of DOACs, potentially lowering DOAC levels and elevating thromboembolism risk, comes mainly from in vitro and animal studies.

“Research in humans is lacking and complicated in interpretation by inconsistent findings and methodological limitations,” she said.

The investigators wanted to address the “clinical uncertainty” surrounding the real-world relevance of enzyme-inducing antiseizure medications and DOAC interactions but conducting a randomized trial “would be neither feasible nor ethical,” said Ms. Acton. 

Using healthcare claims data from October 2010 to September 2021, the researchers conducted an active comparator, new-user cohort study among a nationally representative sample of adults with epilepsy who had been co-prescribed these drugs. 

They compared thromboembolic and major bleeding event rates between exposure to DOACs with enzyme-inducing antiseizure medications vs exposure to DOACs with non-enzyme inducing antiseizure medications.

Enzyme-inducing antiseizure medications included in the study were carbamazepine, oxcarbazepine, phenobarbital, phenytoin, primidone, and topiramate. Non-enzyme-inducing antiseizure medications included gabapentin, lacosamide, lamotrigine, levetiracetam, and pregabalin.

The researchers used data-adaptive high-dimensional propensity score matching to control for “hundreds and hundreds” of observed confounders, and proxies for unobserved confounders, said Ms. Acton. They identified outcomes based on validated diagnostic coding algorithms for thromboembolic and major bleeding events and estimated adjusted hazard ratios (aHRs) using Cox proportional hazard models with robust variance estimators to account for clustering within matched pairs.
 

Reduced Risk of Major Bleeding 

Outcomes were analyzed in three separate cohorts. These included patients on DOACs for any indication (indication-agnostic); those on DOACs for atrial fibrillation (AF); and those taking DOACs for deep vein thrombus/pulmonary embolism (DVT/PE).

In the indication-agnostic analysis, the investigators examined thromboembolic events among 5989 episodes in patients taking both DOACs and enzyme-inducing antiseizure medications, compared witha reference group of 14,671 episodes in patients taking DOACs and non-enzyme-inducing antiseizure medications.

The reference group was generally older and had a greater prevalence of a number of major comorbidities compared with the exposed group, noted Ms. Acton.

For the indication-agnostic analysis, the aHR was 1.11 (95% CI 0.89-1.39). Results were similar for the AF indication (aHR 1.10; 95% CI 0.82-1.46) and for the DVT/PE indication (aHR 1.11; 95% CI 0.81-1.51).

“This research provides large-scale, real-world evidence enzyme-inducing antiseizure medication use alongside DOACs does not significantly elevate risk of thromboembolic events among a nationally representative epilepsy population,” said Ms. Acton.

However, “it’s always important to consider risk factors for thromboembolic and bleeding events at the level of the individual patient,” she added.

With respect to major bleeding events, there was a slightly reduced risk in the exposed group, specifically in the analysis of subjects with atrial fibrillation, where the aHR was 0.63 (95% CI 0.44-0.89).

“A potential explanation may be pharmacokinetic interaction with enzyme-inducing antiseizure medications occurring to a degree that lowers DOAC levels without necessarily negating therapeutic effects,” said Ms. Acton.

However, she cautioned that more research is needed.

As for the differential potency among the various enzyme-inducing antiseizure medications studied, Ms. Acton said results from a secondary analysis in the atrial fibrillation assessment that removed the potentially less potent enzyme inducers, oxcarbazepine and topiramate, didn’t significantly change the study results.
 

‘Really Great News’

Commenting on the findings for this news organization, epilepsy expert Daniel M. Goldenholz, MD, PhD, assistant professor of Neurology, Harvard Beth Israel Deaconess Medical Center, Boston, Massachusetts, said the finding of no meaningful difference between DOAC plus enzyme-inducing medications vs DOACs plus non-enzyme-inducing medications is encouraging.

“This study asks a very important question at the population level and appropriately tries to control for present and hidden factors using a propensity matching approach,” he said.

The fact that the data support no difference in terms of thromboembolic events “is really great news” for patients taking an enzyme-inducing antiseizure medication who need to use a DOAC, he said.

While some patients or clinicians might consider transitioning off an enzyme-inducing antiseizure medication, this can lead to new side effects and potentially higher drug costs. “Knowing that a transition may be unnecessary is exciting,” said Dr. Goldenholz.

However, he’s concerned the 1.5-year observation period may not be long enough to see a true effect of these drug combinations.

He also noted that due to the “theoretical higher risk,” patients combining DOACs with enzyme-inducing drugs typically need extra monitoring, which may be less practical outside the US. This suggests “the result may not necessarily generalize outside high-income countries,” he said.

Dr. Goldenholz emphasized that the data are preliminary. “As always, I look forward to a full peer-reviewed study before forming final conclusions.”

The study was supported by the US Department of Health and Human Services’ National Institute of Neurological Disorders and Stroke.

Ms. Acton and Dr. Goldenholz report no relevant financial relationships.

A version of this article appeared on Medscape.com.

ORLANDO — Combining an enzyme-inducing antiseizure medication with a direct-acting oral anticoagulant (DOAC) does not significantly increase the risk of thromboembolic events in patients with epilepsy, preliminary results of a new study show.

These new data are important, “particularly when we’re talking about a more global perspective, given the vital role of enzyme-inducing antiseizure medications in epilepsy care across many middle- and low-income countries where they may be the only readily available treatment options,” said study investigator Emily K. Acton, PhD candidate in epidemiology and a medical student, University of Pennsylvania Perelman School of Medicine, Philadelphia, and University of Illinois College of Medicine, Chicago. 

The findings also suggest that use of enzyme-inducing antiseizure medication with DOACs may be associated with a reduction in major bleeding events, although Ms. Acton stressed this requires more research.

The findings were presented at the American Epilepsy Society annual meeting.
 

Important Implications

Enzyme-inducing antiseizure medications may induce key drug metabolizing enzymes that result in wide-ranging interactions, Ms. Acton told this news organization. “But, in many cases, the clinical significance of these pharmacokinetic interactions is not completely understood.”

This has important implications for managing anticoagulation, said Ms. Acton. “The ease of DOAC use, and growing evidence of the drugs’ safety and efficacy compared to vitamin K antagonists, has led to widespread shifts in clinical practice towards DOACs.”

Due to the relative novelty of DOACs, their interaction profiles have been less than complete, she explained. Evidence that enzyme-inducing antiseizure medications may reduce absorption and accelerate metabolism of DOACs, potentially lowering DOAC levels and elevating thromboembolism risk, comes mainly from in vitro and animal studies.

“Research in humans is lacking and complicated in interpretation by inconsistent findings and methodological limitations,” she said.

The investigators wanted to address the “clinical uncertainty” surrounding the real-world relevance of enzyme-inducing antiseizure medications and DOAC interactions but conducting a randomized trial “would be neither feasible nor ethical,” said Ms. Acton. 

Using healthcare claims data from October 2010 to September 2021, the researchers conducted an active comparator, new-user cohort study among a nationally representative sample of adults with epilepsy who had been co-prescribed these drugs. 

They compared thromboembolic and major bleeding event rates between exposure to DOACs with enzyme-inducing antiseizure medications vs exposure to DOACs with non-enzyme inducing antiseizure medications.

Enzyme-inducing antiseizure medications included in the study were carbamazepine, oxcarbazepine, phenobarbital, phenytoin, primidone, and topiramate. Non-enzyme-inducing antiseizure medications included gabapentin, lacosamide, lamotrigine, levetiracetam, and pregabalin.

The researchers used data-adaptive high-dimensional propensity score matching to control for “hundreds and hundreds” of observed confounders, and proxies for unobserved confounders, said Ms. Acton. They identified outcomes based on validated diagnostic coding algorithms for thromboembolic and major bleeding events and estimated adjusted hazard ratios (aHRs) using Cox proportional hazard models with robust variance estimators to account for clustering within matched pairs.
 

Reduced Risk of Major Bleeding 

Outcomes were analyzed in three separate cohorts. These included patients on DOACs for any indication (indication-agnostic); those on DOACs for atrial fibrillation (AF); and those taking DOACs for deep vein thrombus/pulmonary embolism (DVT/PE).

In the indication-agnostic analysis, the investigators examined thromboembolic events among 5989 episodes in patients taking both DOACs and enzyme-inducing antiseizure medications, compared witha reference group of 14,671 episodes in patients taking DOACs and non-enzyme-inducing antiseizure medications.

The reference group was generally older and had a greater prevalence of a number of major comorbidities compared with the exposed group, noted Ms. Acton.

For the indication-agnostic analysis, the aHR was 1.11 (95% CI 0.89-1.39). Results were similar for the AF indication (aHR 1.10; 95% CI 0.82-1.46) and for the DVT/PE indication (aHR 1.11; 95% CI 0.81-1.51).

“This research provides large-scale, real-world evidence enzyme-inducing antiseizure medication use alongside DOACs does not significantly elevate risk of thromboembolic events among a nationally representative epilepsy population,” said Ms. Acton.

However, “it’s always important to consider risk factors for thromboembolic and bleeding events at the level of the individual patient,” she added.

With respect to major bleeding events, there was a slightly reduced risk in the exposed group, specifically in the analysis of subjects with atrial fibrillation, where the aHR was 0.63 (95% CI 0.44-0.89).

“A potential explanation may be pharmacokinetic interaction with enzyme-inducing antiseizure medications occurring to a degree that lowers DOAC levels without necessarily negating therapeutic effects,” said Ms. Acton.

However, she cautioned that more research is needed.

As for the differential potency among the various enzyme-inducing antiseizure medications studied, Ms. Acton said results from a secondary analysis in the atrial fibrillation assessment that removed the potentially less potent enzyme inducers, oxcarbazepine and topiramate, didn’t significantly change the study results.
 

‘Really Great News’

Commenting on the findings for this news organization, epilepsy expert Daniel M. Goldenholz, MD, PhD, assistant professor of Neurology, Harvard Beth Israel Deaconess Medical Center, Boston, Massachusetts, said the finding of no meaningful difference between DOAC plus enzyme-inducing medications vs DOACs plus non-enzyme-inducing medications is encouraging.

“This study asks a very important question at the population level and appropriately tries to control for present and hidden factors using a propensity matching approach,” he said.

The fact that the data support no difference in terms of thromboembolic events “is really great news” for patients taking an enzyme-inducing antiseizure medication who need to use a DOAC, he said.

While some patients or clinicians might consider transitioning off an enzyme-inducing antiseizure medication, this can lead to new side effects and potentially higher drug costs. “Knowing that a transition may be unnecessary is exciting,” said Dr. Goldenholz.

However, he’s concerned the 1.5-year observation period may not be long enough to see a true effect of these drug combinations.

He also noted that due to the “theoretical higher risk,” patients combining DOACs with enzyme-inducing drugs typically need extra monitoring, which may be less practical outside the US. This suggests “the result may not necessarily generalize outside high-income countries,” he said.

Dr. Goldenholz emphasized that the data are preliminary. “As always, I look forward to a full peer-reviewed study before forming final conclusions.”

The study was supported by the US Department of Health and Human Services’ National Institute of Neurological Disorders and Stroke.

Ms. Acton and Dr. Goldenholz report no relevant financial relationships.

A version of this article appeared on Medscape.com.

ORLANDO — Combining an enzyme-inducing antiseizure medication with a direct-acting oral anticoagulant (DOAC) does not significantly increase the risk of thromboembolic events in patients with epilepsy, preliminary results of a new study show.

These new data are important, “particularly when we’re talking about a more global perspective, given the vital role of enzyme-inducing antiseizure medications in epilepsy care across many middle- and low-income countries where they may be the only readily available treatment options,” said study investigator Emily K. Acton, PhD candidate in epidemiology and a medical student, University of Pennsylvania Perelman School of Medicine, Philadelphia, and University of Illinois College of Medicine, Chicago. 

The findings also suggest that use of enzyme-inducing antiseizure medication with DOACs may be associated with a reduction in major bleeding events, although Ms. Acton stressed this requires more research.

The findings were presented at the American Epilepsy Society annual meeting.
 

Important Implications

Enzyme-inducing antiseizure medications may induce key drug metabolizing enzymes that result in wide-ranging interactions, Ms. Acton told this news organization. “But, in many cases, the clinical significance of these pharmacokinetic interactions is not completely understood.”

This has important implications for managing anticoagulation, said Ms. Acton. “The ease of DOAC use, and growing evidence of the drugs’ safety and efficacy compared to vitamin K antagonists, has led to widespread shifts in clinical practice towards DOACs.”

Due to the relative novelty of DOACs, their interaction profiles have been less than complete, she explained. Evidence that enzyme-inducing antiseizure medications may reduce absorption and accelerate metabolism of DOACs, potentially lowering DOAC levels and elevating thromboembolism risk, comes mainly from in vitro and animal studies.

“Research in humans is lacking and complicated in interpretation by inconsistent findings and methodological limitations,” she said.

The investigators wanted to address the “clinical uncertainty” surrounding the real-world relevance of enzyme-inducing antiseizure medications and DOAC interactions but conducting a randomized trial “would be neither feasible nor ethical,” said Ms. Acton. 

Using healthcare claims data from October 2010 to September 2021, the researchers conducted an active comparator, new-user cohort study among a nationally representative sample of adults with epilepsy who had been co-prescribed these drugs. 

They compared thromboembolic and major bleeding event rates between exposure to DOACs with enzyme-inducing antiseizure medications vs exposure to DOACs with non-enzyme inducing antiseizure medications.

Enzyme-inducing antiseizure medications included in the study were carbamazepine, oxcarbazepine, phenobarbital, phenytoin, primidone, and topiramate. Non-enzyme-inducing antiseizure medications included gabapentin, lacosamide, lamotrigine, levetiracetam, and pregabalin.

The researchers used data-adaptive high-dimensional propensity score matching to control for “hundreds and hundreds” of observed confounders, and proxies for unobserved confounders, said Ms. Acton. They identified outcomes based on validated diagnostic coding algorithms for thromboembolic and major bleeding events and estimated adjusted hazard ratios (aHRs) using Cox proportional hazard models with robust variance estimators to account for clustering within matched pairs.
 

Reduced Risk of Major Bleeding 

Outcomes were analyzed in three separate cohorts. These included patients on DOACs for any indication (indication-agnostic); those on DOACs for atrial fibrillation (AF); and those taking DOACs for deep vein thrombus/pulmonary embolism (DVT/PE).

In the indication-agnostic analysis, the investigators examined thromboembolic events among 5989 episodes in patients taking both DOACs and enzyme-inducing antiseizure medications, compared witha reference group of 14,671 episodes in patients taking DOACs and non-enzyme-inducing antiseizure medications.

The reference group was generally older and had a greater prevalence of a number of major comorbidities compared with the exposed group, noted Ms. Acton.

For the indication-agnostic analysis, the aHR was 1.11 (95% CI 0.89-1.39). Results were similar for the AF indication (aHR 1.10; 95% CI 0.82-1.46) and for the DVT/PE indication (aHR 1.11; 95% CI 0.81-1.51).

“This research provides large-scale, real-world evidence enzyme-inducing antiseizure medication use alongside DOACs does not significantly elevate risk of thromboembolic events among a nationally representative epilepsy population,” said Ms. Acton.

However, “it’s always important to consider risk factors for thromboembolic and bleeding events at the level of the individual patient,” she added.

With respect to major bleeding events, there was a slightly reduced risk in the exposed group, specifically in the analysis of subjects with atrial fibrillation, where the aHR was 0.63 (95% CI 0.44-0.89).

“A potential explanation may be pharmacokinetic interaction with enzyme-inducing antiseizure medications occurring to a degree that lowers DOAC levels without necessarily negating therapeutic effects,” said Ms. Acton.

However, she cautioned that more research is needed.

As for the differential potency among the various enzyme-inducing antiseizure medications studied, Ms. Acton said results from a secondary analysis in the atrial fibrillation assessment that removed the potentially less potent enzyme inducers, oxcarbazepine and topiramate, didn’t significantly change the study results.
 

‘Really Great News’

Commenting on the findings for this news organization, epilepsy expert Daniel M. Goldenholz, MD, PhD, assistant professor of Neurology, Harvard Beth Israel Deaconess Medical Center, Boston, Massachusetts, said the finding of no meaningful difference between DOAC plus enzyme-inducing medications vs DOACs plus non-enzyme-inducing medications is encouraging.

“This study asks a very important question at the population level and appropriately tries to control for present and hidden factors using a propensity matching approach,” he said.

The fact that the data support no difference in terms of thromboembolic events “is really great news” for patients taking an enzyme-inducing antiseizure medication who need to use a DOAC, he said.

While some patients or clinicians might consider transitioning off an enzyme-inducing antiseizure medication, this can lead to new side effects and potentially higher drug costs. “Knowing that a transition may be unnecessary is exciting,” said Dr. Goldenholz.

However, he’s concerned the 1.5-year observation period may not be long enough to see a true effect of these drug combinations.

He also noted that due to the “theoretical higher risk,” patients combining DOACs with enzyme-inducing drugs typically need extra monitoring, which may be less practical outside the US. This suggests “the result may not necessarily generalize outside high-income countries,” he said.

Dr. Goldenholz emphasized that the data are preliminary. “As always, I look forward to a full peer-reviewed study before forming final conclusions.”

The study was supported by the US Department of Health and Human Services’ National Institute of Neurological Disorders and Stroke.

Ms. Acton and Dr. Goldenholz report no relevant financial relationships.

A version of this article appeared on Medscape.com.

The mechanisms underlying poststroke depression (PSD), a common and debilitating complication of stroke, are unclear. Is it neurobiological, psychosocial, or both?

Two studies offer new insight into this question. In the first, investigators systematically reviewed studies comparing stroke and non-stroke participants with depression and found the groups were similar in most dimensions of depressive symptoms. But surprisingly, anhedonia was less severe in patients with PSD compared with non-stroke controls, and those with PSD also showed greater emotional dysregulation.

“Our findings support previous recommendations that clinicians should adapt the provision of psychological support to the specific needs and difficulties of stroke survivors,” said lead author Joshua Blake, DClinPsy, lecturer in clinical psychology, University of East Anglia, Norwich, United Kingdom.

The study was published online in Neuropsychology Review

A second study used a machine learning algorithm to analyze blood samples from adults who had suffered a stroke, determining whether plasma protein data could predict mood and identifying potential proteins associated with mood in these patients.

“We can now look at a stroke survivor’s blood and predict their mood,” senior author Marion Buckwalter, MD, PhD, professor of neurology and neurosurgery at Stanford Medicine, California, said in a news release. “This means there is a genuine association between what’s happening in the blood and what’s happening with a person’s mood. It also means that, down the road, we may be able to develop new treatments for PSD.”

The study was published in November 2023 in Brain, Behavior, and Immunity.
 

‘Surprising’ Findings

“There has long been uncertainty over whether PSD might differ in its causes, phenomenology, and treatability, due to the presence of brain injury, related biological changes, and the psychosocial context unique to this population,” Dr. Blake said. “We felt that understanding symptomatologic similarities and differences would constructively contribute to this debate.”

The researchers reviewed 12 papers that sampled both stroke and non-stroke participants. “We compared profiles of depression symptoms, correlation strengths of individual depression symptoms with general depression, and latent item severity,” Dr. Blake reported.

They extracted 38 symptoms from five standardized depression tools and then organized the symptoms into nine dimensions.

They found mostly nonsignificant differences between patients with PSD and non-stroke controls in most dimensions, including negative affect, negative cognitions, somatic features, anxiety/worry, and suicidal ideation. Those with PSD more frequently had cognitive impairment, and “work inhibition” was more common in PSD.

But the most striking finding was greater severity/prevalence of emotional dysregulation in PSD vs non-stroke depression and also less anhedonia.

Dr. Blake acknowledged being “surprised.”

One possible explanation is that stroke recovery “appears to be a highly emotional journey, with extreme findings of both positive and negative emotions reported by survivors as they psychologically adjust,” which might be protective against anhedonia, he suggested.

Moreover, neurologically driven emotional dysregulation “may similarly reduce experiences of anhedonia.”

However, there was a “considerable risk of bias in many of the included studies, meaning it’s important that these findings are experimentally confirmed before stronger conclusions about phenomenological differences can be drawn,” he cautioned.
 

Common, Undertreated

Dr. Buckwalter said her team was motivated to conduct the research because PSD is among the top problems reported by chronic stroke patients, and for most, it is not adequately treated.

However, “despite the high prevalence of PSD, it is very poorly studied in the chronic time period.” In particular, PSD isn’t “well understood at a molecular level.”

She added that inflammation is a “promising candidate” as a mechanism, since neuroinflammation occurs in the stroke scar for decades, and chronic peripheral inflammation can produce neuroinflammation. Aberrant immune activation has also been implicated in major depression without stroke. But large studies with broad panels of plasma biomarkers are lacking in PSD.

To address this gap, the researchers used a proteomic approach. They recruited 85 chronic stroke patients (mean age, 65 years [interquartile range, 55-71], 41.2% female, 65.9% White, 17.6% Asian, and 0% Black) from the Stanford Stroke Recovery Program. Participants were between 5 months and 9 years after an ischemic stroke.

They analyzed a comprehensive panel of 1196 proteins in plasma samples, applying a machine learning algorithm to see whether the plasma protein levels “could be used to predict mood scores, using either the proteomics data alone or adding age and time since stroke.” The proteomics data were then incorporated into multivariable regression models, along with relevant clinical features, to ascertain the model’s predictive ability.

Mood was assessed using the Stroke Impact Scale mood questionnaire, with participants’ mood dichotomized into better mood (> 63) or worse mood (≤ 63).
 

‘Beautiful Mechanistic Model’

Machine learning verified a relationship between plasma proteomic data and mood, with the most accurate prediction occurring when the researchers added age and time since the stroke to the analysis.

Independent univariate analyses identified 202 proteins that were most highly correlated with mood in PSD. These were then organized into functional groups, including immune proteins, integrins, growth factors, synaptic function proteins, serotonin activity-related proteins, and cell death and stress-related functional groupings.

Although no single protein could predict depression, significant changes in levels of several proteins were found in PSD patients. A high proportion (45%) were proteins previously implicated in major depression, “likely providing a link to the underlying mechanisms of chronic PSD,” the authors stated.

Moreover, 80% of correlated immune proteins were higher in the plasma of people with worse mood, and several immune proteins known to have anti-inflammatory effects were reduced in those with worse mood.

And several pro-inflammatory cytokines were implicated. For example, interleukin 6, which has been extensively studied as a potential plasma marker of major depression in non-stroke cohorts, was significantly elevated in patients with worse mood after stroke (P = .0325), «implicating a broadly overactive immune system in PSD.»

“We demonstrated for the first time that we can use plasma protein measurements to predict mood in people with chronic stroke,” Dr. Buckwalter summarized. “This means there is a biological correlate of mood but [it] doesn’t tell us causality.”

To tease out causality, the researchers used their own data, as well as information from a literature review of previous studies, to assemble a model of how the immune response following a stroke could change both serotonin and brain plasticity.

“We used the most highly correlated proteins to construct a beautiful mechanistic model of how poststroke depression may work and how it may relate to mechanisms in major depression,” Dr. Buckwalter said.

The model “posits an increased inflammatory response that leads to decreased tryptophan, serotonin, and less synaptic function, all of which contribute to symptoms of depression.”

Currently, selective serotonin reuptake inhibitors represent the “best treatment” for people with PSD, but “unfortunately they don’t work for many patients,” Dr. Buckwalter noted. The findings “provide clues as to other molecular targets that are candidates novel therapies for poststroke depression.”

Dr. Blake commented that the proteomic study “complements the work by us and others interested in understanding PSD.”

Mood disorders “must be understood in terms of the dynamic relationships between structural neurological alterations, cellular and microbiological changes, psychological processes, and the person’s interactions with their social landscape,” Dr. Blake said.
 

New Treatments on the Horizon?

Gustavo C. Medeiros, MD, assistant professor, Department of Psychiatry, of the University of Maryland School of Medicine, Baltimore, said that knowing which individuals are more likely to develop PSD “allows treatment teams to implement earlier and more intensive interventions in those who are at higher risk.”

The findings [of the proteomic study] may also “help clarify the neurobiological correlates of PSD…[which] may help the development of new treatments that target these neurobiological changes,” said Dr. Medeiros, who wasn’t involved with either study.

However, he warned, “we should interpret their results with caution due to methodological reasons, including the relatively small sample size.”

Also commenting, Bruce Ovbiagele, MD, MSc, MAS, MBA, MLS, professor of neurology, UCSF Weill Institute for Neurosciences, California, said the proteomic study has some “clear limitations,” including the lack of Black or African American patients in the cohort, which limits generalizability, “since we know that Black and African American people are disproportionately affected by stroke and have very high rates of PSD and very severe presentation.”

The study by Dr. Blake et al. “was interesting because the phenotype of depressive symptoms after stroke differs from what’s seen in the general population, and the authors figured out a way to better understand the nuances of such differences,” said Dr. Ovbiagele, who wasn’t involved with either study.

He said he was also surprised by the finding regarding anhedonia and suggested that the findings be replicated in a study directly comparing patients with PSD and patients with depression from the general population.

The study by Bidoki et al. was funded by AHA/Paul Allen Foundation, the Leducq Stroke-IMPaCT Transatlantic Network of Excellence (MSB), the Wu Tsai Neurosciences Institute (MSB), the Alfred E. Mann Foundation (NA), and an Alzheimer’s Association Research Fellowship to one of the authors. No source of funding was listed for the study by Dr. Blake et al. The authors of both studies, Dr. Medeiros and Dr. Ovbiagele, declare no relevant financial relationships.

A version of this article appeared on Medscape.com.

The mechanisms underlying poststroke depression (PSD), a common and debilitating complication of stroke, are unclear. Is it neurobiological, psychosocial, or both?

Two studies offer new insight into this question. In the first, investigators systematically reviewed studies comparing stroke and non-stroke participants with depression and found the groups were similar in most dimensions of depressive symptoms. But surprisingly, anhedonia was less severe in patients with PSD compared with non-stroke controls, and those with PSD also showed greater emotional dysregulation.

“Our findings support previous recommendations that clinicians should adapt the provision of psychological support to the specific needs and difficulties of stroke survivors,” said lead author Joshua Blake, DClinPsy, lecturer in clinical psychology, University of East Anglia, Norwich, United Kingdom.

The study was published online in Neuropsychology Review

A second study used a machine learning algorithm to analyze blood samples from adults who had suffered a stroke, determining whether plasma protein data could predict mood and identifying potential proteins associated with mood in these patients.

“We can now look at a stroke survivor’s blood and predict their mood,” senior author Marion Buckwalter, MD, PhD, professor of neurology and neurosurgery at Stanford Medicine, California, said in a news release. “This means there is a genuine association between what’s happening in the blood and what’s happening with a person’s mood. It also means that, down the road, we may be able to develop new treatments for PSD.”

The study was published in November 2023 in Brain, Behavior, and Immunity.
 

‘Surprising’ Findings

“There has long been uncertainty over whether PSD might differ in its causes, phenomenology, and treatability, due to the presence of brain injury, related biological changes, and the psychosocial context unique to this population,” Dr. Blake said. “We felt that understanding symptomatologic similarities and differences would constructively contribute to this debate.”

The researchers reviewed 12 papers that sampled both stroke and non-stroke participants. “We compared profiles of depression symptoms, correlation strengths of individual depression symptoms with general depression, and latent item severity,” Dr. Blake reported.

They extracted 38 symptoms from five standardized depression tools and then organized the symptoms into nine dimensions.

They found mostly nonsignificant differences between patients with PSD and non-stroke controls in most dimensions, including negative affect, negative cognitions, somatic features, anxiety/worry, and suicidal ideation. Those with PSD more frequently had cognitive impairment, and “work inhibition” was more common in PSD.

But the most striking finding was greater severity/prevalence of emotional dysregulation in PSD vs non-stroke depression and also less anhedonia.

Dr. Blake acknowledged being “surprised.”

One possible explanation is that stroke recovery “appears to be a highly emotional journey, with extreme findings of both positive and negative emotions reported by survivors as they psychologically adjust,” which might be protective against anhedonia, he suggested.

Moreover, neurologically driven emotional dysregulation “may similarly reduce experiences of anhedonia.”

However, there was a “considerable risk of bias in many of the included studies, meaning it’s important that these findings are experimentally confirmed before stronger conclusions about phenomenological differences can be drawn,” he cautioned.
 

Common, Undertreated

Dr. Buckwalter said her team was motivated to conduct the research because PSD is among the top problems reported by chronic stroke patients, and for most, it is not adequately treated.

However, “despite the high prevalence of PSD, it is very poorly studied in the chronic time period.” In particular, PSD isn’t “well understood at a molecular level.”

She added that inflammation is a “promising candidate” as a mechanism, since neuroinflammation occurs in the stroke scar for decades, and chronic peripheral inflammation can produce neuroinflammation. Aberrant immune activation has also been implicated in major depression without stroke. But large studies with broad panels of plasma biomarkers are lacking in PSD.

To address this gap, the researchers used a proteomic approach. They recruited 85 chronic stroke patients (mean age, 65 years [interquartile range, 55-71], 41.2% female, 65.9% White, 17.6% Asian, and 0% Black) from the Stanford Stroke Recovery Program. Participants were between 5 months and 9 years after an ischemic stroke.

They analyzed a comprehensive panel of 1196 proteins in plasma samples, applying a machine learning algorithm to see whether the plasma protein levels “could be used to predict mood scores, using either the proteomics data alone or adding age and time since stroke.” The proteomics data were then incorporated into multivariable regression models, along with relevant clinical features, to ascertain the model’s predictive ability.

Mood was assessed using the Stroke Impact Scale mood questionnaire, with participants’ mood dichotomized into better mood (> 63) or worse mood (≤ 63).
 

‘Beautiful Mechanistic Model’

Machine learning verified a relationship between plasma proteomic data and mood, with the most accurate prediction occurring when the researchers added age and time since the stroke to the analysis.

Independent univariate analyses identified 202 proteins that were most highly correlated with mood in PSD. These were then organized into functional groups, including immune proteins, integrins, growth factors, synaptic function proteins, serotonin activity-related proteins, and cell death and stress-related functional groupings.

Although no single protein could predict depression, significant changes in levels of several proteins were found in PSD patients. A high proportion (45%) were proteins previously implicated in major depression, “likely providing a link to the underlying mechanisms of chronic PSD,” the authors stated.

Moreover, 80% of correlated immune proteins were higher in the plasma of people with worse mood, and several immune proteins known to have anti-inflammatory effects were reduced in those with worse mood.

And several pro-inflammatory cytokines were implicated. For example, interleukin 6, which has been extensively studied as a potential plasma marker of major depression in non-stroke cohorts, was significantly elevated in patients with worse mood after stroke (P = .0325), «implicating a broadly overactive immune system in PSD.»

“We demonstrated for the first time that we can use plasma protein measurements to predict mood in people with chronic stroke,” Dr. Buckwalter summarized. “This means there is a biological correlate of mood but [it] doesn’t tell us causality.”

To tease out causality, the researchers used their own data, as well as information from a literature review of previous studies, to assemble a model of how the immune response following a stroke could change both serotonin and brain plasticity.

“We used the most highly correlated proteins to construct a beautiful mechanistic model of how poststroke depression may work and how it may relate to mechanisms in major depression,” Dr. Buckwalter said.

The model “posits an increased inflammatory response that leads to decreased tryptophan, serotonin, and less synaptic function, all of which contribute to symptoms of depression.”

Currently, selective serotonin reuptake inhibitors represent the “best treatment” for people with PSD, but “unfortunately they don’t work for many patients,” Dr. Buckwalter noted. The findings “provide clues as to other molecular targets that are candidates novel therapies for poststroke depression.”

Dr. Blake commented that the proteomic study “complements the work by us and others interested in understanding PSD.”

Mood disorders “must be understood in terms of the dynamic relationships between structural neurological alterations, cellular and microbiological changes, psychological processes, and the person’s interactions with their social landscape,” Dr. Blake said.
 

New Treatments on the Horizon?

Gustavo C. Medeiros, MD, assistant professor, Department of Psychiatry, of the University of Maryland School of Medicine, Baltimore, said that knowing which individuals are more likely to develop PSD “allows treatment teams to implement earlier and more intensive interventions in those who are at higher risk.”

The findings [of the proteomic study] may also “help clarify the neurobiological correlates of PSD…[which] may help the development of new treatments that target these neurobiological changes,” said Dr. Medeiros, who wasn’t involved with either study.

However, he warned, “we should interpret their results with caution due to methodological reasons, including the relatively small sample size.”

Also commenting, Bruce Ovbiagele, MD, MSc, MAS, MBA, MLS, professor of neurology, UCSF Weill Institute for Neurosciences, California, said the proteomic study has some “clear limitations,” including the lack of Black or African American patients in the cohort, which limits generalizability, “since we know that Black and African American people are disproportionately affected by stroke and have very high rates of PSD and very severe presentation.”

The study by Dr. Blake et al. “was interesting because the phenotype of depressive symptoms after stroke differs from what’s seen in the general population, and the authors figured out a way to better understand the nuances of such differences,” said Dr. Ovbiagele, who wasn’t involved with either study.

He said he was also surprised by the finding regarding anhedonia and suggested that the findings be replicated in a study directly comparing patients with PSD and patients with depression from the general population.

The study by Bidoki et al. was funded by AHA/Paul Allen Foundation, the Leducq Stroke-IMPaCT Transatlantic Network of Excellence (MSB), the Wu Tsai Neurosciences Institute (MSB), the Alfred E. Mann Foundation (NA), and an Alzheimer’s Association Research Fellowship to one of the authors. No source of funding was listed for the study by Dr. Blake et al. The authors of both studies, Dr. Medeiros and Dr. Ovbiagele, declare no relevant financial relationships.

A version of this article appeared on Medscape.com.

The mechanisms underlying poststroke depression (PSD), a common and debilitating complication of stroke, are unclear. Is it neurobiological, psychosocial, or both?

Two studies offer new insight into this question. In the first, investigators systematically reviewed studies comparing stroke and non-stroke participants with depression and found the groups were similar in most dimensions of depressive symptoms. But surprisingly, anhedonia was less severe in patients with PSD compared with non-stroke controls, and those with PSD also showed greater emotional dysregulation.

“Our findings support previous recommendations that clinicians should adapt the provision of psychological support to the specific needs and difficulties of stroke survivors,” said lead author Joshua Blake, DClinPsy, lecturer in clinical psychology, University of East Anglia, Norwich, United Kingdom.

The study was published online in Neuropsychology Review

A second study used a machine learning algorithm to analyze blood samples from adults who had suffered a stroke, determining whether plasma protein data could predict mood and identifying potential proteins associated with mood in these patients.

“We can now look at a stroke survivor’s blood and predict their mood,” senior author Marion Buckwalter, MD, PhD, professor of neurology and neurosurgery at Stanford Medicine, California, said in a news release. “This means there is a genuine association between what’s happening in the blood and what’s happening with a person’s mood. It also means that, down the road, we may be able to develop new treatments for PSD.”

The study was published in November 2023 in Brain, Behavior, and Immunity.
 

‘Surprising’ Findings

“There has long been uncertainty over whether PSD might differ in its causes, phenomenology, and treatability, due to the presence of brain injury, related biological changes, and the psychosocial context unique to this population,” Dr. Blake said. “We felt that understanding symptomatologic similarities and differences would constructively contribute to this debate.”

The researchers reviewed 12 papers that sampled both stroke and non-stroke participants. “We compared profiles of depression symptoms, correlation strengths of individual depression symptoms with general depression, and latent item severity,” Dr. Blake reported.

They extracted 38 symptoms from five standardized depression tools and then organized the symptoms into nine dimensions.

They found mostly nonsignificant differences between patients with PSD and non-stroke controls in most dimensions, including negative affect, negative cognitions, somatic features, anxiety/worry, and suicidal ideation. Those with PSD more frequently had cognitive impairment, and “work inhibition” was more common in PSD.

But the most striking finding was greater severity/prevalence of emotional dysregulation in PSD vs non-stroke depression and also less anhedonia.

Dr. Blake acknowledged being “surprised.”

One possible explanation is that stroke recovery “appears to be a highly emotional journey, with extreme findings of both positive and negative emotions reported by survivors as they psychologically adjust,” which might be protective against anhedonia, he suggested.

Moreover, neurologically driven emotional dysregulation “may similarly reduce experiences of anhedonia.”

However, there was a “considerable risk of bias in many of the included studies, meaning it’s important that these findings are experimentally confirmed before stronger conclusions about phenomenological differences can be drawn,” he cautioned.
 

Common, Undertreated

Dr. Buckwalter said her team was motivated to conduct the research because PSD is among the top problems reported by chronic stroke patients, and for most, it is not adequately treated.

However, “despite the high prevalence of PSD, it is very poorly studied in the chronic time period.” In particular, PSD isn’t “well understood at a molecular level.”

She added that inflammation is a “promising candidate” as a mechanism, since neuroinflammation occurs in the stroke scar for decades, and chronic peripheral inflammation can produce neuroinflammation. Aberrant immune activation has also been implicated in major depression without stroke. But large studies with broad panels of plasma biomarkers are lacking in PSD.

To address this gap, the researchers used a proteomic approach. They recruited 85 chronic stroke patients (mean age, 65 years [interquartile range, 55-71], 41.2% female, 65.9% White, 17.6% Asian, and 0% Black) from the Stanford Stroke Recovery Program. Participants were between 5 months and 9 years after an ischemic stroke.

They analyzed a comprehensive panel of 1196 proteins in plasma samples, applying a machine learning algorithm to see whether the plasma protein levels “could be used to predict mood scores, using either the proteomics data alone or adding age and time since stroke.” The proteomics data were then incorporated into multivariable regression models, along with relevant clinical features, to ascertain the model’s predictive ability.

Mood was assessed using the Stroke Impact Scale mood questionnaire, with participants’ mood dichotomized into better mood (> 63) or worse mood (≤ 63).
 

‘Beautiful Mechanistic Model’

Machine learning verified a relationship between plasma proteomic data and mood, with the most accurate prediction occurring when the researchers added age and time since the stroke to the analysis.

Independent univariate analyses identified 202 proteins that were most highly correlated with mood in PSD. These were then organized into functional groups, including immune proteins, integrins, growth factors, synaptic function proteins, serotonin activity-related proteins, and cell death and stress-related functional groupings.

Although no single protein could predict depression, significant changes in levels of several proteins were found in PSD patients. A high proportion (45%) were proteins previously implicated in major depression, “likely providing a link to the underlying mechanisms of chronic PSD,” the authors stated.

Moreover, 80% of correlated immune proteins were higher in the plasma of people with worse mood, and several immune proteins known to have anti-inflammatory effects were reduced in those with worse mood.

And several pro-inflammatory cytokines were implicated. For example, interleukin 6, which has been extensively studied as a potential plasma marker of major depression in non-stroke cohorts, was significantly elevated in patients with worse mood after stroke (P = .0325), «implicating a broadly overactive immune system in PSD.»

“We demonstrated for the first time that we can use plasma protein measurements to predict mood in people with chronic stroke,” Dr. Buckwalter summarized. “This means there is a biological correlate of mood but [it] doesn’t tell us causality.”

To tease out causality, the researchers used their own data, as well as information from a literature review of previous studies, to assemble a model of how the immune response following a stroke could change both serotonin and brain plasticity.

“We used the most highly correlated proteins to construct a beautiful mechanistic model of how poststroke depression may work and how it may relate to mechanisms in major depression,” Dr. Buckwalter said.

The model “posits an increased inflammatory response that leads to decreased tryptophan, serotonin, and less synaptic function, all of which contribute to symptoms of depression.”

Currently, selective serotonin reuptake inhibitors represent the “best treatment” for people with PSD, but “unfortunately they don’t work for many patients,” Dr. Buckwalter noted. The findings “provide clues as to other molecular targets that are candidates novel therapies for poststroke depression.”

Dr. Blake commented that the proteomic study “complements the work by us and others interested in understanding PSD.”

Mood disorders “must be understood in terms of the dynamic relationships between structural neurological alterations, cellular and microbiological changes, psychological processes, and the person’s interactions with their social landscape,” Dr. Blake said.
 

New Treatments on the Horizon?

Gustavo C. Medeiros, MD, assistant professor, Department of Psychiatry, of the University of Maryland School of Medicine, Baltimore, said that knowing which individuals are more likely to develop PSD “allows treatment teams to implement earlier and more intensive interventions in those who are at higher risk.”

The findings [of the proteomic study] may also “help clarify the neurobiological correlates of PSD…[which] may help the development of new treatments that target these neurobiological changes,” said Dr. Medeiros, who wasn’t involved with either study.

However, he warned, “we should interpret their results with caution due to methodological reasons, including the relatively small sample size.”

Also commenting, Bruce Ovbiagele, MD, MSc, MAS, MBA, MLS, professor of neurology, UCSF Weill Institute for Neurosciences, California, said the proteomic study has some “clear limitations,” including the lack of Black or African American patients in the cohort, which limits generalizability, “since we know that Black and African American people are disproportionately affected by stroke and have very high rates of PSD and very severe presentation.”

The study by Dr. Blake et al. “was interesting because the phenotype of depressive symptoms after stroke differs from what’s seen in the general population, and the authors figured out a way to better understand the nuances of such differences,” said Dr. Ovbiagele, who wasn’t involved with either study.

He said he was also surprised by the finding regarding anhedonia and suggested that the findings be replicated in a study directly comparing patients with PSD and patients with depression from the general population.

The study by Bidoki et al. was funded by AHA/Paul Allen Foundation, the Leducq Stroke-IMPaCT Transatlantic Network of Excellence (MSB), the Wu Tsai Neurosciences Institute (MSB), the Alfred E. Mann Foundation (NA), and an Alzheimer’s Association Research Fellowship to one of the authors. No source of funding was listed for the study by Dr. Blake et al. The authors of both studies, Dr. Medeiros and Dr. Ovbiagele, declare no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE: 

Dual antiplatelet therapy (DAPT) with clopidogrel-aspirin given within 72 hours of a mild ischemic stroke or a high-risk transient ischemic attack (TIA) shows a greater risk reduction for new stroke than aspirin alone, although with a higher bleeding risk.

METHODOLOGY:

• The INSPIRES, a double-blind, placebo-controlled trial, involved patients with mild ischemic stroke or high-risk TIA of presumed atherosclerotic cause who had not undergone thrombolysis or thrombectomy.
• A total of 6100 patients were randomly assigned to receive clopidogrel plus aspirin or matching clopidogrel placebo plus aspirin within 72 hours after symptom onset.
• The occurrence of any new stroke (ischemic or hemorrhagic) within 90 days was the primary efficacy outcome.
• The primary safety outcome was moderate to severe bleeding, also assessed within 90 days.

TAKEAWAY:

• Within 24 hours of symptom onset, 12.8% of patients were assigned to each treatment group, and the remaining 87.2% were assigned within the time window of 24-72 hours.
• (7.3% vs 9.2%; marginal estimated hazard ratio [HR], 0.79; P =.008).
• The risk of a composite cardiovascular event and ischemic stroke were also 20%-25% lower with aspirin-clopidogrel combo vs aspirin alone.
• Moderate to severe bleeding was low in both groups (<1%), but the risk was double in patients who received DAPT vs aspirin alone (HR, 2.08; P =.03).

IN PRACTICE:

In an accompanying editorial, Anthony S. Kim, MD from the UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, commented, “The current trial provides evidence to support expanding the time window for dual antiplatelet therapy to 72 hours.” He also warned against administering DAPT to “patients with heightened bleeding risks, such as those with a history of cerebral or systemic hemorrhage.”

SOURCE:

Yilong Wang, MD, PhD, who held positions in the Department of Neurology, Beijing Tiantan Hospital, and several other institutions, was the corresponding author of this study. This study was published online December 28 in the New England Journal of Medicine.

LIMITATIONS:

• Patients with stroke of presumed cardioembolic origin, those with moderate or severe stroke, and those who had undergone thrombolysis or thrombectomy were excluded from this study.
• Of the enrolled participants, 98.5% belonged to the Han Chinese ethnic group.

DISCLOSURES:

This study was supported by grants from the National Natural Science Foundation of China, the National Key R&D Program of China, and other sources. Some authors declared receiving grants or contracts or serving as consultants in various sources.

A version of this article appeared on Medscape.com.

TOPLINE: 

Dual antiplatelet therapy (DAPT) with clopidogrel-aspirin given within 72 hours of a mild ischemic stroke or a high-risk transient ischemic attack (TIA) shows a greater risk reduction for new stroke than aspirin alone, although with a higher bleeding risk.

METHODOLOGY:

• The INSPIRES, a double-blind, placebo-controlled trial, involved patients with mild ischemic stroke or high-risk TIA of presumed atherosclerotic cause who had not undergone thrombolysis or thrombectomy.
• A total of 6100 patients were randomly assigned to receive clopidogrel plus aspirin or matching clopidogrel placebo plus aspirin within 72 hours after symptom onset.
• The occurrence of any new stroke (ischemic or hemorrhagic) within 90 days was the primary efficacy outcome.
• The primary safety outcome was moderate to severe bleeding, also assessed within 90 days.

TAKEAWAY:

• Within 24 hours of symptom onset, 12.8% of patients were assigned to each treatment group, and the remaining 87.2% were assigned within the time window of 24-72 hours.
• (7.3% vs 9.2%; marginal estimated hazard ratio [HR], 0.79; P =.008).
• The risk of a composite cardiovascular event and ischemic stroke were also 20%-25% lower with aspirin-clopidogrel combo vs aspirin alone.
• Moderate to severe bleeding was low in both groups (<1%), but the risk was double in patients who received DAPT vs aspirin alone (HR, 2.08; P =.03).

IN PRACTICE:

In an accompanying editorial, Anthony S. Kim, MD from the UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, commented, “The current trial provides evidence to support expanding the time window for dual antiplatelet therapy to 72 hours.” He also warned against administering DAPT to “patients with heightened bleeding risks, such as those with a history of cerebral or systemic hemorrhage.”

SOURCE:

Yilong Wang, MD, PhD, who held positions in the Department of Neurology, Beijing Tiantan Hospital, and several other institutions, was the corresponding author of this study. This study was published online December 28 in the New England Journal of Medicine.

LIMITATIONS:

• Patients with stroke of presumed cardioembolic origin, those with moderate or severe stroke, and those who had undergone thrombolysis or thrombectomy were excluded from this study.
• Of the enrolled participants, 98.5% belonged to the Han Chinese ethnic group.

DISCLOSURES:

This study was supported by grants from the National Natural Science Foundation of China, the National Key R&D Program of China, and other sources. Some authors declared receiving grants or contracts or serving as consultants in various sources.

A version of this article appeared on Medscape.com.

TOPLINE: 

Dual antiplatelet therapy (DAPT) with clopidogrel-aspirin given within 72 hours of a mild ischemic stroke or a high-risk transient ischemic attack (TIA) shows a greater risk reduction for new stroke than aspirin alone, although with a higher bleeding risk.

METHODOLOGY:

• The INSPIRES, a double-blind, placebo-controlled trial, involved patients with mild ischemic stroke or high-risk TIA of presumed atherosclerotic cause who had not undergone thrombolysis or thrombectomy.
• A total of 6100 patients were randomly assigned to receive clopidogrel plus aspirin or matching clopidogrel placebo plus aspirin within 72 hours after symptom onset.
• The occurrence of any new stroke (ischemic or hemorrhagic) within 90 days was the primary efficacy outcome.
• The primary safety outcome was moderate to severe bleeding, also assessed within 90 days.

TAKEAWAY:

• Within 24 hours of symptom onset, 12.8% of patients were assigned to each treatment group, and the remaining 87.2% were assigned within the time window of 24-72 hours.
• (7.3% vs 9.2%; marginal estimated hazard ratio [HR], 0.79; P =.008).
• The risk of a composite cardiovascular event and ischemic stroke were also 20%-25% lower with aspirin-clopidogrel combo vs aspirin alone.
• Moderate to severe bleeding was low in both groups (<1%), but the risk was double in patients who received DAPT vs aspirin alone (HR, 2.08; P =.03).

IN PRACTICE:

In an accompanying editorial, Anthony S. Kim, MD from the UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, commented, “The current trial provides evidence to support expanding the time window for dual antiplatelet therapy to 72 hours.” He also warned against administering DAPT to “patients with heightened bleeding risks, such as those with a history of cerebral or systemic hemorrhage.”

SOURCE:

Yilong Wang, MD, PhD, who held positions in the Department of Neurology, Beijing Tiantan Hospital, and several other institutions, was the corresponding author of this study. This study was published online December 28 in the New England Journal of Medicine.

LIMITATIONS:

• Patients with stroke of presumed cardioembolic origin, those with moderate or severe stroke, and those who had undergone thrombolysis or thrombectomy were excluded from this study.
• Of the enrolled participants, 98.5% belonged to the Han Chinese ethnic group.

DISCLOSURES:

This study was supported by grants from the National Natural Science Foundation of China, the National Key R&D Program of China, and other sources. Some authors declared receiving grants or contracts or serving as consultants in various sources.

A version of this article appeared on Medscape.com.

TOPLINE:

Removing race and incorporating social determinants of health (SDOH) into the pooled cohort risk equations (PCEs) for predicting atherosclerotic cardiovascular disease (ASCVD) outcomes made no difference to patients’ risk scores.

METHODOLOGY:

• Primary prevention guidelines recommend using risk prediction algorithms to assess the 10-year ASCVD risk, with the currently recommended PCEs including race.
• Researchers evaluated the incremental value of revised risk prediction equations excluding race and introducing SDOH in 11,638 participants from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort.
• Participants were aged between 45 and 79 years, had no history of ASCVD, and were not taking statins.
• Participants were followed up to 10 years for incident ASCVD, including myocardial infarction, coronary heart disease death, and fatal and nonfatal stroke.

TAKEAWAY:

• Risk prediction equations performed similarly in race- and sex-stratified PCEs (C-statistic [95% CI])
• Black female: 0.71 (0.68-0.75); Black male: 0.68 (0.64-0.73); White female: 0.77 (0.74-0.80); White male: 0.68 (0.65-0.71)
• Race-free sex-specific PCEs yielded similar discrimination as race- and sex-stratified PCEs (C-statistic [95% CI]):
• Black female: 0.71 (0.67-0.75); Black male: 0.68 (0.63-0.72); White female: 0.76 (0.73-0.80); White male: 0.68 (0.65-0.71)
• The addition of SDOH to race-free sex-specific PCEs did not improve model performance (C-statistic [95% CI]):
• Black female: 0.72 (0.68-0.76); Black male: 0.68 (0.64-0.72); White female: 0.77 (0.74-0.80); White male: 0.68 (0.65-0.71)

IN PRACTICE:

“The major takeaway is we need to rethink the idea of race in cardiovascular risk prediction,” lead author Arnab Ghosh, MD, assistant professor of medicine at Weill Cornell Medical College and a hospitalist at New York-Presbyterian/Weill Cornell Medical Center, said in a press release.

“It’s essential for clinicians and scientists to consider how to appropriately address the health effects of race as a social construct, which has contributed to health disparities in cardiovascular outcomes,” Dr. Ghosh added.

SOURCE:

The study led by Dr. Ghosh was published online on December 6, 2023, in JAMA Cardiology with an Editor’s Note.

LIMITATIONS:

The study required informed consent for inclusion, which may have led to selection bias.

The REGARDS cohort’s SDOH may not have captured all social and socioeconomic influences on ASCVD outcomes.

DISCLOSURES:

The research was funded by the National Institute of Neurological Disorders and Stroke and the National Institute on Aging of the National Institutes of Health, Department of Health and Human Services, and others. Some authors declared receiving funding, grants, or personal fees from various sources.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Removing race and incorporating social determinants of health (SDOH) into the pooled cohort risk equations (PCEs) for predicting atherosclerotic cardiovascular disease (ASCVD) outcomes made no difference to patients’ risk scores.

METHODOLOGY:

• Primary prevention guidelines recommend using risk prediction algorithms to assess the 10-year ASCVD risk, with the currently recommended PCEs including race.
• Researchers evaluated the incremental value of revised risk prediction equations excluding race and introducing SDOH in 11,638 participants from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort.
• Participants were aged between 45 and 79 years, had no history of ASCVD, and were not taking statins.
• Participants were followed up to 10 years for incident ASCVD, including myocardial infarction, coronary heart disease death, and fatal and nonfatal stroke.

TAKEAWAY:

• Risk prediction equations performed similarly in race- and sex-stratified PCEs (C-statistic [95% CI])
• Black female: 0.71 (0.68-0.75); Black male: 0.68 (0.64-0.73); White female: 0.77 (0.74-0.80); White male: 0.68 (0.65-0.71)
• Race-free sex-specific PCEs yielded similar discrimination as race- and sex-stratified PCEs (C-statistic [95% CI]):
• Black female: 0.71 (0.67-0.75); Black male: 0.68 (0.63-0.72); White female: 0.76 (0.73-0.80); White male: 0.68 (0.65-0.71)
• The addition of SDOH to race-free sex-specific PCEs did not improve model performance (C-statistic [95% CI]):
• Black female: 0.72 (0.68-0.76); Black male: 0.68 (0.64-0.72); White female: 0.77 (0.74-0.80); White male: 0.68 (0.65-0.71)

IN PRACTICE:

“The major takeaway is we need to rethink the idea of race in cardiovascular risk prediction,” lead author Arnab Ghosh, MD, assistant professor of medicine at Weill Cornell Medical College and a hospitalist at New York-Presbyterian/Weill Cornell Medical Center, said in a press release.

“It’s essential for clinicians and scientists to consider how to appropriately address the health effects of race as a social construct, which has contributed to health disparities in cardiovascular outcomes,” Dr. Ghosh added.

SOURCE:

The study led by Dr. Ghosh was published online on December 6, 2023, in JAMA Cardiology with an Editor’s Note.

LIMITATIONS:

The study required informed consent for inclusion, which may have led to selection bias.

The REGARDS cohort’s SDOH may not have captured all social and socioeconomic influences on ASCVD outcomes.

DISCLOSURES:

The research was funded by the National Institute of Neurological Disorders and Stroke and the National Institute on Aging of the National Institutes of Health, Department of Health and Human Services, and others. Some authors declared receiving funding, grants, or personal fees from various sources.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Removing race and incorporating social determinants of health (SDOH) into the pooled cohort risk equations (PCEs) for predicting atherosclerotic cardiovascular disease (ASCVD) outcomes made no difference to patients’ risk scores.

METHODOLOGY:

• Primary prevention guidelines recommend using risk prediction algorithms to assess the 10-year ASCVD risk, with the currently recommended PCEs including race.
• Researchers evaluated the incremental value of revised risk prediction equations excluding race and introducing SDOH in 11,638 participants from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort.
• Participants were aged between 45 and 79 years, had no history of ASCVD, and were not taking statins.
• Participants were followed up to 10 years for incident ASCVD, including myocardial infarction, coronary heart disease death, and fatal and nonfatal stroke.

TAKEAWAY:

• Risk prediction equations performed similarly in race- and sex-stratified PCEs (C-statistic [95% CI])
• Black female: 0.71 (0.68-0.75); Black male: 0.68 (0.64-0.73); White female: 0.77 (0.74-0.80); White male: 0.68 (0.65-0.71)
• Race-free sex-specific PCEs yielded similar discrimination as race- and sex-stratified PCEs (C-statistic [95% CI]):
• Black female: 0.71 (0.67-0.75); Black male: 0.68 (0.63-0.72); White female: 0.76 (0.73-0.80); White male: 0.68 (0.65-0.71)
• The addition of SDOH to race-free sex-specific PCEs did not improve model performance (C-statistic [95% CI]):
• Black female: 0.72 (0.68-0.76); Black male: 0.68 (0.64-0.72); White female: 0.77 (0.74-0.80); White male: 0.68 (0.65-0.71)

IN PRACTICE:

“The major takeaway is we need to rethink the idea of race in cardiovascular risk prediction,” lead author Arnab Ghosh, MD, assistant professor of medicine at Weill Cornell Medical College and a hospitalist at New York-Presbyterian/Weill Cornell Medical Center, said in a press release.

“It’s essential for clinicians and scientists to consider how to appropriately address the health effects of race as a social construct, which has contributed to health disparities in cardiovascular outcomes,” Dr. Ghosh added.

SOURCE:

The study led by Dr. Ghosh was published online on December 6, 2023, in JAMA Cardiology with an Editor’s Note.

LIMITATIONS:

The study required informed consent for inclusion, which may have led to selection bias.

The REGARDS cohort’s SDOH may not have captured all social and socioeconomic influences on ASCVD outcomes.

DISCLOSURES:

The research was funded by the National Institute of Neurological Disorders and Stroke and the National Institute on Aging of the National Institutes of Health, Department of Health and Human Services, and others. Some authors declared receiving funding, grants, or personal fees from various sources.
 

A version of this article appeared on Medscape.com.

A multicomponent exercise program that includes strength, aerobic, agility, and balance training exercises is cost-effective and results in improved cognition among stroke survivors, compared with a balance and tone control group, according to a new analysis.

On the other hand, a program consisting of cognitive and social enrichment activities that includes memory, brain training, and group social games entailed higher costs, compared with the balance and tone group, which included stretches, deep breathing and relaxation techniques, posture education, and core control exercises.

“Cognitive impairment is experienced in approximately one-third of stroke survivors,” study author Jennifer Davis, PhD, a Canada research chair in applied health economics and assistant professor of management at the University of British Columbia in Kelowna, said in an interview.

“The economic evaluation of the exercise intervention demonstrated that the multicomponent exercise program provided good value for the money when comparing costs and cognitive outcomes,” she said. However, “impacts on health-related quality of life were not observed.”

The study was published online November 30 in JAMA Network Open. 
 

Comparing Three Approaches

Despite improved care, patients with stroke often face challenges with physical function, cognitive abilities, and quality of life, the authors wrote. Among older adults, in particular, cognitive deficits remain prevalent and are associated with increased risks for dementia, mortality, and increased burdens for patients, caregivers, and health systems.

Numerous interventions have shown promise for post-stroke cognitive rehabilitation, including exercise and cognitive training, the authors wrote. Research hasn’t indicated which programs offer the most efficient or cost-effective options, however.

Dr. Davis and colleagues conducted an economic evaluation alongside the Vitality study, a three-group randomized clinical trial that examined the efficacy of improving cognitive function among patients with chronic stroke through a multicomponent exercise program, cognitive and social enrichment activities, or a control group with balance and tone activities. 

The economic evaluation team included a cost-effectiveness analysis (based on incremental cost per cognitive function change) and a cost-utility analysis (incremental cost per quality-adjusted life-year [QALY] gained). The researchers used a cost-effectiveness threshold of CAD $50,000 (Canadian dollars) per QALY for the cost-utility analysis, which was based on precedent treatment in Canada.

The clinical trial included 120 community-dwelling adults aged 55 years and older who had a stroke at least 12 months before the study. Based in the Vancouver metropolitan area, participants were randomly assigned to twice-weekly, 60-minute classes led by trained instructors for 26 weeks. The mean age was 71 years, and 62% of participants were men.

Exercise Effective

Overall, the balance and tone control group had the lowest delivery cost at CAD $777 per person, followed by CAD $1090 per person for the exercise group and CAD $1492 per person for the cognitive and social enrichment group.

After the 6-month intervention, the mean cognitive scores were –0.192 for the exercise group, –0.184 for the cognitive and social enrichment group, and –0.171 for the balance and tone group, indicating better cognitive function across all three groups.

In the cost-effectiveness analysis, the exercise intervention was costlier but more effective than the control group, with an incremental cost-effectiveness ratio (ICER) of CAD –$8823.

In the cost-utility analysis, the exercise intervention was cost saving (less costly and more effective), compared with the control group, with an ICER of CAD –$3381 per QALY gained at the end of the intervention and an ICER of CAD –$154,198 per QALY gained at the end of the 12-month follow-up period. The cognitive and social enrichment program was more costly and more effective than the control group, with an ICER of CAD $101,687 per QALY gained at the end of the intervention and an ICER of CAD $331,306 per QALY gained at the end of the follow-up period.

In additional analyses, the exercise group had the lowest healthcare resource utilization due to lower healthcare costs for physician visits and lab tests.

“This study provides initial data that suggests multicomponent exercise may be a cost-effective solution for combating cognitive decline among stroke survivors,” said Dr. Davis.

Overall, exercise was cost-effective for improving cognitive function but not quality of life among participants. The clinical trial was powered to detect changes in cognitive function rather than quality of life, so it lacked statistical power to detect differences in quality of life, said Dr. Davis.

Exercise programs and cognitive and social enrichment programs show promise for improving cognitive function after stroke, the authors wrote, though future research should focus on optimizing cost-effectiveness and enhancing health-related quality of life.

Considering Additional Benefits

Commenting on the study, Alan Tam, MD, a physiatrist at the Toronto Rehabilitation Institute’s Brain Rehabilitation Program, said, “The authors show that within the timeframe of their analysis, there is a trend to cost-effectiveness for the cognitive intervention being offered.” Dr. Tam did not participate in the research.

“However, the finding is not robust, as less than 50% of their simulations would meet their acceptability level they have defined,” he said. “Given that most of the cost of the intervention is up front, but the benefits are likely lifelong, potentially taking the 12-month analysis to a lifetime analysis would show more significant findings.”

Dr. Tam researches factors associated with brain injury rehabilitation and has explored the cost-effectiveness of a high-intensity outpatient stroke rehabilitation program.

“Presenting this type of work is important,” he said. “While there are interventions that do not meet our definition of statistical significance, especially in the rehabilitation world, there can still be a benefit for patients and health systems.”

The primary study was funded by the Canadian Institutes of Health Research (CIHR) and the Jack Brown and Family Alzheimer Research Foundation Society. Dr. Davis reported receiving grants from the CIHR and Michael Smith Health Research BC during the conduct of the study. Dr. Tam reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

A multicomponent exercise program that includes strength, aerobic, agility, and balance training exercises is cost-effective and results in improved cognition among stroke survivors, compared with a balance and tone control group, according to a new analysis.

On the other hand, a program consisting of cognitive and social enrichment activities that includes memory, brain training, and group social games entailed higher costs, compared with the balance and tone group, which included stretches, deep breathing and relaxation techniques, posture education, and core control exercises.

“Cognitive impairment is experienced in approximately one-third of stroke survivors,” study author Jennifer Davis, PhD, a Canada research chair in applied health economics and assistant professor of management at the University of British Columbia in Kelowna, said in an interview.

“The economic evaluation of the exercise intervention demonstrated that the multicomponent exercise program provided good value for the money when comparing costs and cognitive outcomes,” she said. However, “impacts on health-related quality of life were not observed.”

The study was published online November 30 in JAMA Network Open. 
 

Comparing Three Approaches

Despite improved care, patients with stroke often face challenges with physical function, cognitive abilities, and quality of life, the authors wrote. Among older adults, in particular, cognitive deficits remain prevalent and are associated with increased risks for dementia, mortality, and increased burdens for patients, caregivers, and health systems.

Numerous interventions have shown promise for post-stroke cognitive rehabilitation, including exercise and cognitive training, the authors wrote. Research hasn’t indicated which programs offer the most efficient or cost-effective options, however.

Dr. Davis and colleagues conducted an economic evaluation alongside the Vitality study, a three-group randomized clinical trial that examined the efficacy of improving cognitive function among patients with chronic stroke through a multicomponent exercise program, cognitive and social enrichment activities, or a control group with balance and tone activities. 

The economic evaluation team included a cost-effectiveness analysis (based on incremental cost per cognitive function change) and a cost-utility analysis (incremental cost per quality-adjusted life-year [QALY] gained). The researchers used a cost-effectiveness threshold of CAD $50,000 (Canadian dollars) per QALY for the cost-utility analysis, which was based on precedent treatment in Canada.

The clinical trial included 120 community-dwelling adults aged 55 years and older who had a stroke at least 12 months before the study. Based in the Vancouver metropolitan area, participants were randomly assigned to twice-weekly, 60-minute classes led by trained instructors for 26 weeks. The mean age was 71 years, and 62% of participants were men.

Exercise Effective

Overall, the balance and tone control group had the lowest delivery cost at CAD $777 per person, followed by CAD $1090 per person for the exercise group and CAD $1492 per person for the cognitive and social enrichment group.

After the 6-month intervention, the mean cognitive scores were –0.192 for the exercise group, –0.184 for the cognitive and social enrichment group, and –0.171 for the balance and tone group, indicating better cognitive function across all three groups.

In the cost-effectiveness analysis, the exercise intervention was costlier but more effective than the control group, with an incremental cost-effectiveness ratio (ICER) of CAD –$8823.

In the cost-utility analysis, the exercise intervention was cost saving (less costly and more effective), compared with the control group, with an ICER of CAD –$3381 per QALY gained at the end of the intervention and an ICER of CAD –$154,198 per QALY gained at the end of the 12-month follow-up period. The cognitive and social enrichment program was more costly and more effective than the control group, with an ICER of CAD $101,687 per QALY gained at the end of the intervention and an ICER of CAD $331,306 per QALY gained at the end of the follow-up period.

In additional analyses, the exercise group had the lowest healthcare resource utilization due to lower healthcare costs for physician visits and lab tests.

“This study provides initial data that suggests multicomponent exercise may be a cost-effective solution for combating cognitive decline among stroke survivors,” said Dr. Davis.

Overall, exercise was cost-effective for improving cognitive function but not quality of life among participants. The clinical trial was powered to detect changes in cognitive function rather than quality of life, so it lacked statistical power to detect differences in quality of life, said Dr. Davis.

Exercise programs and cognitive and social enrichment programs show promise for improving cognitive function after stroke, the authors wrote, though future research should focus on optimizing cost-effectiveness and enhancing health-related quality of life.

Considering Additional Benefits

Commenting on the study, Alan Tam, MD, a physiatrist at the Toronto Rehabilitation Institute’s Brain Rehabilitation Program, said, “The authors show that within the timeframe of their analysis, there is a trend to cost-effectiveness for the cognitive intervention being offered.” Dr. Tam did not participate in the research.

“However, the finding is not robust, as less than 50% of their simulations would meet their acceptability level they have defined,” he said. “Given that most of the cost of the intervention is up front, but the benefits are likely lifelong, potentially taking the 12-month analysis to a lifetime analysis would show more significant findings.”

Dr. Tam researches factors associated with brain injury rehabilitation and has explored the cost-effectiveness of a high-intensity outpatient stroke rehabilitation program.

“Presenting this type of work is important,” he said. “While there are interventions that do not meet our definition of statistical significance, especially in the rehabilitation world, there can still be a benefit for patients and health systems.”

The primary study was funded by the Canadian Institutes of Health Research (CIHR) and the Jack Brown and Family Alzheimer Research Foundation Society. Dr. Davis reported receiving grants from the CIHR and Michael Smith Health Research BC during the conduct of the study. Dr. Tam reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

A multicomponent exercise program that includes strength, aerobic, agility, and balance training exercises is cost-effective and results in improved cognition among stroke survivors, compared with a balance and tone control group, according to a new analysis.

On the other hand, a program consisting of cognitive and social enrichment activities that includes memory, brain training, and group social games entailed higher costs, compared with the balance and tone group, which included stretches, deep breathing and relaxation techniques, posture education, and core control exercises.

“Cognitive impairment is experienced in approximately one-third of stroke survivors,” study author Jennifer Davis, PhD, a Canada research chair in applied health economics and assistant professor of management at the University of British Columbia in Kelowna, said in an interview.

“The economic evaluation of the exercise intervention demonstrated that the multicomponent exercise program provided good value for the money when comparing costs and cognitive outcomes,” she said. However, “impacts on health-related quality of life were not observed.”

The study was published online November 30 in JAMA Network Open. 
 

Comparing Three Approaches

Despite improved care, patients with stroke often face challenges with physical function, cognitive abilities, and quality of life, the authors wrote. Among older adults, in particular, cognitive deficits remain prevalent and are associated with increased risks for dementia, mortality, and increased burdens for patients, caregivers, and health systems.

Numerous interventions have shown promise for post-stroke cognitive rehabilitation, including exercise and cognitive training, the authors wrote. Research hasn’t indicated which programs offer the most efficient or cost-effective options, however.

Dr. Davis and colleagues conducted an economic evaluation alongside the Vitality study, a three-group randomized clinical trial that examined the efficacy of improving cognitive function among patients with chronic stroke through a multicomponent exercise program, cognitive and social enrichment activities, or a control group with balance and tone activities. 

The economic evaluation team included a cost-effectiveness analysis (based on incremental cost per cognitive function change) and a cost-utility analysis (incremental cost per quality-adjusted life-year [QALY] gained). The researchers used a cost-effectiveness threshold of CAD $50,000 (Canadian dollars) per QALY for the cost-utility analysis, which was based on precedent treatment in Canada.

The clinical trial included 120 community-dwelling adults aged 55 years and older who had a stroke at least 12 months before the study. Based in the Vancouver metropolitan area, participants were randomly assigned to twice-weekly, 60-minute classes led by trained instructors for 26 weeks. The mean age was 71 years, and 62% of participants were men.

Exercise Effective

Overall, the balance and tone control group had the lowest delivery cost at CAD $777 per person, followed by CAD $1090 per person for the exercise group and CAD $1492 per person for the cognitive and social enrichment group.

After the 6-month intervention, the mean cognitive scores were –0.192 for the exercise group, –0.184 for the cognitive and social enrichment group, and –0.171 for the balance and tone group, indicating better cognitive function across all three groups.

In the cost-effectiveness analysis, the exercise intervention was costlier but more effective than the control group, with an incremental cost-effectiveness ratio (ICER) of CAD –$8823.

In the cost-utility analysis, the exercise intervention was cost saving (less costly and more effective), compared with the control group, with an ICER of CAD –$3381 per QALY gained at the end of the intervention and an ICER of CAD –$154,198 per QALY gained at the end of the 12-month follow-up period. The cognitive and social enrichment program was more costly and more effective than the control group, with an ICER of CAD $101,687 per QALY gained at the end of the intervention and an ICER of CAD $331,306 per QALY gained at the end of the follow-up period.

In additional analyses, the exercise group had the lowest healthcare resource utilization due to lower healthcare costs for physician visits and lab tests.

“This study provides initial data that suggests multicomponent exercise may be a cost-effective solution for combating cognitive decline among stroke survivors,” said Dr. Davis.

Overall, exercise was cost-effective for improving cognitive function but not quality of life among participants. The clinical trial was powered to detect changes in cognitive function rather than quality of life, so it lacked statistical power to detect differences in quality of life, said Dr. Davis.

Exercise programs and cognitive and social enrichment programs show promise for improving cognitive function after stroke, the authors wrote, though future research should focus on optimizing cost-effectiveness and enhancing health-related quality of life.

Considering Additional Benefits

Commenting on the study, Alan Tam, MD, a physiatrist at the Toronto Rehabilitation Institute’s Brain Rehabilitation Program, said, “The authors show that within the timeframe of their analysis, there is a trend to cost-effectiveness for the cognitive intervention being offered.” Dr. Tam did not participate in the research.

“However, the finding is not robust, as less than 50% of their simulations would meet their acceptability level they have defined,” he said. “Given that most of the cost of the intervention is up front, but the benefits are likely lifelong, potentially taking the 12-month analysis to a lifetime analysis would show more significant findings.”

Dr. Tam researches factors associated with brain injury rehabilitation and has explored the cost-effectiveness of a high-intensity outpatient stroke rehabilitation program.

“Presenting this type of work is important,” he said. “While there are interventions that do not meet our definition of statistical significance, especially in the rehabilitation world, there can still be a benefit for patients and health systems.”

The primary study was funded by the Canadian Institutes of Health Research (CIHR) and the Jack Brown and Family Alzheimer Research Foundation Society. Dr. Davis reported receiving grants from the CIHR and Michael Smith Health Research BC during the conduct of the study. Dr. Tam reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Repairing patent foramen ovale (PFO) and other right-to-left shunt disorders for the prevention of migraine has generated mixed results, but the potential for these repairs also includes reducing the risk of stroke, according to a discussion at the 2023 Scottsdale Headache Symposium.

In two clinical trials evaluating whether PFO closure reduces migraine risk, the primary endpoints were not met, but a signal of benefit on secondary endpoints and the association between PFO, migraine, and stroke are among the reasons that PFO closure should be reevaluated, according to Andrew Charles MD, Director of the Goldberg Migraine Program, University of California, Los Angeles.

UCLA

One Intervention, Two Potential Benefits

Fixing these defects is therefore at least theoretically attractive for preventing both migraine and stroke, but Dr. Charles said the opportunity for preventing both migraine and stroke is most attractive in migraine patients who have additional stroke risk factors.

Use of oral contraceptives, which produce a hypercoagulable state, is an example.

“Are these the people we should really be thinking about if they have PFO and migraine, particularly migraine with aura?” Dr. Charles asked.

The association between right-to-left shunts and migraine is strong. Although PFO is common, presenting in 20%-25% of the adult population, it has been found in up to 50% of individuals who have migraine with aura. In patients with migraine but no aura, the prevalence of PFO has been estimated to be approximately 35% or still somewhat elevated relative to the general population.
 

Primary Endpoint Missed in Clinical Trials

The question of whether risk of migraine can be reduced with repair of PFO or other right-to-left shunts remains unresolved. In two high-quality randomized trials undertaken in PFO repair, neither met its primary endpoint. In one of these, called PRIMA, which was terminated early for slow enrollment, the reduction in mean headache attacks was not significant relative to medical therapy.

In the second, called PREMIUM, device closure of PFO also failed to significantly reduce migraine attacks over sham procedure although it was associated with complete migraine remission (10% vs 1%).

A pooled analysis of these two studies that was conducted subsequently concluded that PFO closure reduces mean monthly migraine days (-3.1 vs. -1.9 days; P = -.02) and increases the likelihood of complete migraine cessation (9% vs. 0.7%; P < .001), but Dr. Charles pointed out the primary endpoint was migraine attacks not migraine days, so other analyses can only be considered hypothesis-generating.

There are several reasons to relook at the relationship between migraine and PFO but the potential to prevent both migraine and stroke with PFO closure could be one of the most important.

Several years ago, Dr. Charles and his coinvestigators from UCLA evaluated more than 700 ischemic strokes. Of these, 127 strokes were characterized as cryptogenic because of lack of another identifiable etiology. While 59% of these patients had PFO, which is several times higher than the general population, the prevalence of PFO in patients with a cryptogenic stroke and a history of migraine was 79% in this published study.

“So, in this group of patients who did not have any other clear cause for a stroke, a diagnosis of PFO was very much overrepresented,” Dr. Charles said.
 

Migraine Days Might Be a Better Endpoint

For patients with migraine who have risk factors for stroke, this makes PFO closure an attractive intervention, but a positive randomized trial is needed. Several are underway. Importantly, the trials now enrolling are using migraine days, which was significantly reduced in both PREMIUM and PRIMA, rather than migraine attacks as the primary endpoint.

“Migraine days is now accepted by the Food and Drug Administration as a criterion of benefit,” reported Jonathan Tobis, MD, Research Director, Interventional Cardiology, UCLA David Geffen School of Medicine, Los Angeles.

He explained that the FDA insisted on migraine attacks as the endpoint for the PREMIUM trial, but this was a far more challenging endpoint on which to show a statistical benefit. He emphasized that a new set of trials will now test efficacy on the basis of migraine days.

One of these trials, called RELIEF, which is randomizing patients to device closure of PFO or a sham procedure. Both groups are receiving clopidogrel or prasugrel based on a previous observation that patients who respond to these drugs are also more likely to respond to PFO closure.

Another trial, called COMPETE-2, is comparing PFO closure with a device to aspirin plus a sham closure. This trial is ongoing in China.

Stroke is not being evaluated as an endpoint in either trial, but Dr. Charles suggested that this does warrant attention.

“I would also just put it out there that, apart from simply migraine, this is a therapeutic approach that we might actually think about in terms of helping to prevent stroke in our migraine patients,” he said.

Senior author of a recent meta-analysis of trials evaluating PFO closure and control of migraine, Ling Liu, MD, Department of Neurology, University of Sichuan, Chengdu, China, agreed that PFO closure for the treatment of migraine deserves “a reevaluation.”

In his meta-analysis of three randomized trials, one pooled study, and eight retrospective case series with 1,165 patients, PFO closure was associated with a nearly 75% reduction (odds ratio [OR], 0.259; P = .0048) reduction in migraine days and 50% increase in resolution of migraine in patients with a history of migraine with aura (OR, 1.586; P = .227).

The incidence of stroke was not evaluated in this meta-analysis, but Dr. Liu believes that the evidence of reducing the burden of migraine with PFO closure is compelling. Given the evidence from this meta-analysis that PFO closure is safe, Dr. Liu maintained that a definitive trial is needed “especially for migraine with frequent aura.”

As an interventional cardiologist, Dr. Tobis said that when PFO closures is performed for prevention of stroke in patients with migraine, it often leads to reduced migraine activity and, in some cases, elimination of migraine. Like others, he believes new analyses should be conducted.

“Everyone involved in this field believes there is something there,” Dr. Tobis said. The missing link is a clinical trial to confirm it.

Dr. Charles and Dr. Liu report no potential conflicts of interest. Dr. Tobis reports a financial relationship with Holistick Medical.

Repairing patent foramen ovale (PFO) and other right-to-left shunt disorders for the prevention of migraine has generated mixed results, but the potential for these repairs also includes reducing the risk of stroke, according to a discussion at the 2023 Scottsdale Headache Symposium.

In two clinical trials evaluating whether PFO closure reduces migraine risk, the primary endpoints were not met, but a signal of benefit on secondary endpoints and the association between PFO, migraine, and stroke are among the reasons that PFO closure should be reevaluated, according to Andrew Charles MD, Director of the Goldberg Migraine Program, University of California, Los Angeles.

UCLA

One Intervention, Two Potential Benefits

Fixing these defects is therefore at least theoretically attractive for preventing both migraine and stroke, but Dr. Charles said the opportunity for preventing both migraine and stroke is most attractive in migraine patients who have additional stroke risk factors.

Use of oral contraceptives, which produce a hypercoagulable state, is an example.

“Are these the people we should really be thinking about if they have PFO and migraine, particularly migraine with aura?” Dr. Charles asked.

The association between right-to-left shunts and migraine is strong. Although PFO is common, presenting in 20%-25% of the adult population, it has been found in up to 50% of individuals who have migraine with aura. In patients with migraine but no aura, the prevalence of PFO has been estimated to be approximately 35% or still somewhat elevated relative to the general population.
 

Primary Endpoint Missed in Clinical Trials

The question of whether risk of migraine can be reduced with repair of PFO or other right-to-left shunts remains unresolved. In two high-quality randomized trials undertaken in PFO repair, neither met its primary endpoint. In one of these, called PRIMA, which was terminated early for slow enrollment, the reduction in mean headache attacks was not significant relative to medical therapy.

In the second, called PREMIUM, device closure of PFO also failed to significantly reduce migraine attacks over sham procedure although it was associated with complete migraine remission (10% vs 1%).

A pooled analysis of these two studies that was conducted subsequently concluded that PFO closure reduces mean monthly migraine days (-3.1 vs. -1.9 days; P = -.02) and increases the likelihood of complete migraine cessation (9% vs. 0.7%; P < .001), but Dr. Charles pointed out the primary endpoint was migraine attacks not migraine days, so other analyses can only be considered hypothesis-generating.

There are several reasons to relook at the relationship between migraine and PFO but the potential to prevent both migraine and stroke with PFO closure could be one of the most important.

Several years ago, Dr. Charles and his coinvestigators from UCLA evaluated more than 700 ischemic strokes. Of these, 127 strokes were characterized as cryptogenic because of lack of another identifiable etiology. While 59% of these patients had PFO, which is several times higher than the general population, the prevalence of PFO in patients with a cryptogenic stroke and a history of migraine was 79% in this published study.

“So, in this group of patients who did not have any other clear cause for a stroke, a diagnosis of PFO was very much overrepresented,” Dr. Charles said.
 

Migraine Days Might Be a Better Endpoint

For patients with migraine who have risk factors for stroke, this makes PFO closure an attractive intervention, but a positive randomized trial is needed. Several are underway. Importantly, the trials now enrolling are using migraine days, which was significantly reduced in both PREMIUM and PRIMA, rather than migraine attacks as the primary endpoint.

“Migraine days is now accepted by the Food and Drug Administration as a criterion of benefit,” reported Jonathan Tobis, MD, Research Director, Interventional Cardiology, UCLA David Geffen School of Medicine, Los Angeles.

He explained that the FDA insisted on migraine attacks as the endpoint for the PREMIUM trial, but this was a far more challenging endpoint on which to show a statistical benefit. He emphasized that a new set of trials will now test efficacy on the basis of migraine days.

One of these trials, called RELIEF, which is randomizing patients to device closure of PFO or a sham procedure. Both groups are receiving clopidogrel or prasugrel based on a previous observation that patients who respond to these drugs are also more likely to respond to PFO closure.

Another trial, called COMPETE-2, is comparing PFO closure with a device to aspirin plus a sham closure. This trial is ongoing in China.

Stroke is not being evaluated as an endpoint in either trial, but Dr. Charles suggested that this does warrant attention.

“I would also just put it out there that, apart from simply migraine, this is a therapeutic approach that we might actually think about in terms of helping to prevent stroke in our migraine patients,” he said.

Senior author of a recent meta-analysis of trials evaluating PFO closure and control of migraine, Ling Liu, MD, Department of Neurology, University of Sichuan, Chengdu, China, agreed that PFO closure for the treatment of migraine deserves “a reevaluation.”

In his meta-analysis of three randomized trials, one pooled study, and eight retrospective case series with 1,165 patients, PFO closure was associated with a nearly 75% reduction (odds ratio [OR], 0.259; P = .0048) reduction in migraine days and 50% increase in resolution of migraine in patients with a history of migraine with aura (OR, 1.586; P = .227).

The incidence of stroke was not evaluated in this meta-analysis, but Dr. Liu believes that the evidence of reducing the burden of migraine with PFO closure is compelling. Given the evidence from this meta-analysis that PFO closure is safe, Dr. Liu maintained that a definitive trial is needed “especially for migraine with frequent aura.”

As an interventional cardiologist, Dr. Tobis said that when PFO closures is performed for prevention of stroke in patients with migraine, it often leads to reduced migraine activity and, in some cases, elimination of migraine. Like others, he believes new analyses should be conducted.

“Everyone involved in this field believes there is something there,” Dr. Tobis said. The missing link is a clinical trial to confirm it.

Dr. Charles and Dr. Liu report no potential conflicts of interest. Dr. Tobis reports a financial relationship with Holistick Medical.

Repairing patent foramen ovale (PFO) and other right-to-left shunt disorders for the prevention of migraine has generated mixed results, but the potential for these repairs also includes reducing the risk of stroke, according to a discussion at the 2023 Scottsdale Headache Symposium.

In two clinical trials evaluating whether PFO closure reduces migraine risk, the primary endpoints were not met, but a signal of benefit on secondary endpoints and the association between PFO, migraine, and stroke are among the reasons that PFO closure should be reevaluated, according to Andrew Charles MD, Director of the Goldberg Migraine Program, University of California, Los Angeles.

UCLA

One Intervention, Two Potential Benefits

Fixing these defects is therefore at least theoretically attractive for preventing both migraine and stroke, but Dr. Charles said the opportunity for preventing both migraine and stroke is most attractive in migraine patients who have additional stroke risk factors.

Use of oral contraceptives, which produce a hypercoagulable state, is an example.

“Are these the people we should really be thinking about if they have PFO and migraine, particularly migraine with aura?” Dr. Charles asked.

The association between right-to-left shunts and migraine is strong. Although PFO is common, presenting in 20%-25% of the adult population, it has been found in up to 50% of individuals who have migraine with aura. In patients with migraine but no aura, the prevalence of PFO has been estimated to be approximately 35% or still somewhat elevated relative to the general population.
 

Primary Endpoint Missed in Clinical Trials

The question of whether risk of migraine can be reduced with repair of PFO or other right-to-left shunts remains unresolved. In two high-quality randomized trials undertaken in PFO repair, neither met its primary endpoint. In one of these, called PRIMA, which was terminated early for slow enrollment, the reduction in mean headache attacks was not significant relative to medical therapy.

In the second, called PREMIUM, device closure of PFO also failed to significantly reduce migraine attacks over sham procedure although it was associated with complete migraine remission (10% vs 1%).

A pooled analysis of these two studies that was conducted subsequently concluded that PFO closure reduces mean monthly migraine days (-3.1 vs. -1.9 days; P = -.02) and increases the likelihood of complete migraine cessation (9% vs. 0.7%; P < .001), but Dr. Charles pointed out the primary endpoint was migraine attacks not migraine days, so other analyses can only be considered hypothesis-generating.

There are several reasons to relook at the relationship between migraine and PFO but the potential to prevent both migraine and stroke with PFO closure could be one of the most important.

Several years ago, Dr. Charles and his coinvestigators from UCLA evaluated more than 700 ischemic strokes. Of these, 127 strokes were characterized as cryptogenic because of lack of another identifiable etiology. While 59% of these patients had PFO, which is several times higher than the general population, the prevalence of PFO in patients with a cryptogenic stroke and a history of migraine was 79% in this published study.

“So, in this group of patients who did not have any other clear cause for a stroke, a diagnosis of PFO was very much overrepresented,” Dr. Charles said.
 

Migraine Days Might Be a Better Endpoint

For patients with migraine who have risk factors for stroke, this makes PFO closure an attractive intervention, but a positive randomized trial is needed. Several are underway. Importantly, the trials now enrolling are using migraine days, which was significantly reduced in both PREMIUM and PRIMA, rather than migraine attacks as the primary endpoint.

“Migraine days is now accepted by the Food and Drug Administration as a criterion of benefit,” reported Jonathan Tobis, MD, Research Director, Interventional Cardiology, UCLA David Geffen School of Medicine, Los Angeles.

He explained that the FDA insisted on migraine attacks as the endpoint for the PREMIUM trial, but this was a far more challenging endpoint on which to show a statistical benefit. He emphasized that a new set of trials will now test efficacy on the basis of migraine days.

One of these trials, called RELIEF, which is randomizing patients to device closure of PFO or a sham procedure. Both groups are receiving clopidogrel or prasugrel based on a previous observation that patients who respond to these drugs are also more likely to respond to PFO closure.

Another trial, called COMPETE-2, is comparing PFO closure with a device to aspirin plus a sham closure. This trial is ongoing in China.

Stroke is not being evaluated as an endpoint in either trial, but Dr. Charles suggested that this does warrant attention.

“I would also just put it out there that, apart from simply migraine, this is a therapeutic approach that we might actually think about in terms of helping to prevent stroke in our migraine patients,” he said.

Senior author of a recent meta-analysis of trials evaluating PFO closure and control of migraine, Ling Liu, MD, Department of Neurology, University of Sichuan, Chengdu, China, agreed that PFO closure for the treatment of migraine deserves “a reevaluation.”

In his meta-analysis of three randomized trials, one pooled study, and eight retrospective case series with 1,165 patients, PFO closure was associated with a nearly 75% reduction (odds ratio [OR], 0.259; P = .0048) reduction in migraine days and 50% increase in resolution of migraine in patients with a history of migraine with aura (OR, 1.586; P = .227).

The incidence of stroke was not evaluated in this meta-analysis, but Dr. Liu believes that the evidence of reducing the burden of migraine with PFO closure is compelling. Given the evidence from this meta-analysis that PFO closure is safe, Dr. Liu maintained that a definitive trial is needed “especially for migraine with frequent aura.”

As an interventional cardiologist, Dr. Tobis said that when PFO closures is performed for prevention of stroke in patients with migraine, it often leads to reduced migraine activity and, in some cases, elimination of migraine. Like others, he believes new analyses should be conducted.

“Everyone involved in this field believes there is something there,” Dr. Tobis said. The missing link is a clinical trial to confirm it.

Dr. Charles and Dr. Liu report no potential conflicts of interest. Dr. Tobis reports a financial relationship with Holistick Medical.

TOPLINE:

Left atrial appendage closure was associated with about half as many disabling or fatal strokes and lower mortality after a stroke, compared with dual oral anticoagulant therapy in patients with atrial fibrillation (AFib), new observational research shows.

METHODOLOGY:

• The retrospective registry analysis included 447 adult patients with nonvalvular AFib, mean age 74 years, who were hospitalized with an ischemic stroke, 322 of whom were receiving direct oral anticoagulant (DOAC) therapy, mostly (84%) apixaban or rivaroxaban, and 125 were treated with left atrial appendage closure (LAAC), almost all (97%) with Watchman or Watchman-FLX devices.
• All patients received standard stroke care, monitoring, and treatment as well as physical therapy/rehabilitation.
• For the primary outcome, researchers used the modified Rankin Scale (mRS) to determine disabling (mRS score of 3-5) and fatal (mRS score of 6) strokes at discharge and at 3 months.
• The study adjusted for age, smoking, paroxysmal AFib, prior major bleeding, prior hemorrhagic stroke, medication adherence, and other risk factors.

TAKEAWAY:

• The incidence of disabling or fatal IS was significantly lower with LAAC versus with DOAC at discharge (38.3% vs. 70.3%; P < .001) and at 3 months (33.3% vs. 56.2%; P < .001), even though the LAAC group had more baseline comorbidity, for example, older age, more smokers, and more prior major bleeding.
• There was no significant difference in mortality between groups during hospitalization, but at 3 months, mortality was lower in the LAAC group (14.7% vs. 32.1%; P = .002).
• Multivariate linear regression analysis showed LAAC independently predicted more favorable mRS at discharge (2.8) and 3 months (1.4) (both P < .001) and was associated with less all-cause death at 3 months (odds ratio, 0.28; 95% confidence interval, 0.12-0.64; P = .002).
• Including those that excluded the 14.4% of LAAC patients who also received DOAC therapy, sensitivity analyses patients who got reduced dose DOACs and nonadherent patients yielded nearly identical outcomes to the full cohort analysis.

IN PRACTICE:

“Despite a higher baseline risk profile, patients treated with LAAC who developed IS had better outcomes than those receiving DOAC prophylaxis,” the authors conclude, adding that several ongoing prospective trials could, “shed light on the mechanism(s) responsible for differences in stroke severity.”

SOURCE:

The study was conducted by Mohit K. Turagam, MD, Icahn School of Medicine at Mount Sinai, New York, and colleagues. It was published online in JACC: Clinical Electrophysiology.

LIMITATIONS:

Despite sensitivity analyses and adjustment for risk factors, selection bias, missing data, and other confounding factors could have affected outcomes. The study didn’t evaluate recurrent IS or type and intensity of rehabilitation on outcomes. Lack of imaging data comparing stroke infarct size and volume limits understanding of exact mechanism driving higher stroke severity with DOACs. Because patients who died before reaching hospital weren’t captured in the registry, the actual mortality may be higher than reported.

DISCLOSURES:

Dr. Turagam has served as a consultant for Biosense Webster and Sanofi.

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

TOPLINE:

Left atrial appendage closure was associated with about half as many disabling or fatal strokes and lower mortality after a stroke, compared with dual oral anticoagulant therapy in patients with atrial fibrillation (AFib), new observational research shows.

METHODOLOGY:

• The retrospective registry analysis included 447 adult patients with nonvalvular AFib, mean age 74 years, who were hospitalized with an ischemic stroke, 322 of whom were receiving direct oral anticoagulant (DOAC) therapy, mostly (84%) apixaban or rivaroxaban, and 125 were treated with left atrial appendage closure (LAAC), almost all (97%) with Watchman or Watchman-FLX devices.
• All patients received standard stroke care, monitoring, and treatment as well as physical therapy/rehabilitation.
• For the primary outcome, researchers used the modified Rankin Scale (mRS) to determine disabling (mRS score of 3-5) and fatal (mRS score of 6) strokes at discharge and at 3 months.
• The study adjusted for age, smoking, paroxysmal AFib, prior major bleeding, prior hemorrhagic stroke, medication adherence, and other risk factors.

TAKEAWAY:

• The incidence of disabling or fatal IS was significantly lower with LAAC versus with DOAC at discharge (38.3% vs. 70.3%; P < .001) and at 3 months (33.3% vs. 56.2%; P < .001), even though the LAAC group had more baseline comorbidity, for example, older age, more smokers, and more prior major bleeding.
• There was no significant difference in mortality between groups during hospitalization, but at 3 months, mortality was lower in the LAAC group (14.7% vs. 32.1%; P = .002).
• Multivariate linear regression analysis showed LAAC independently predicted more favorable mRS at discharge (2.8) and 3 months (1.4) (both P < .001) and was associated with less all-cause death at 3 months (odds ratio, 0.28; 95% confidence interval, 0.12-0.64; P = .002).
• Including those that excluded the 14.4% of LAAC patients who also received DOAC therapy, sensitivity analyses patients who got reduced dose DOACs and nonadherent patients yielded nearly identical outcomes to the full cohort analysis.

IN PRACTICE:

“Despite a higher baseline risk profile, patients treated with LAAC who developed IS had better outcomes than those receiving DOAC prophylaxis,” the authors conclude, adding that several ongoing prospective trials could, “shed light on the mechanism(s) responsible for differences in stroke severity.”

SOURCE:

The study was conducted by Mohit K. Turagam, MD, Icahn School of Medicine at Mount Sinai, New York, and colleagues. It was published online in JACC: Clinical Electrophysiology.

LIMITATIONS:

Despite sensitivity analyses and adjustment for risk factors, selection bias, missing data, and other confounding factors could have affected outcomes. The study didn’t evaluate recurrent IS or type and intensity of rehabilitation on outcomes. Lack of imaging data comparing stroke infarct size and volume limits understanding of exact mechanism driving higher stroke severity with DOACs. Because patients who died before reaching hospital weren’t captured in the registry, the actual mortality may be higher than reported.

DISCLOSURES:

Dr. Turagam has served as a consultant for Biosense Webster and Sanofi.

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

TOPLINE:

Left atrial appendage closure was associated with about half as many disabling or fatal strokes and lower mortality after a stroke, compared with dual oral anticoagulant therapy in patients with atrial fibrillation (AFib), new observational research shows.

METHODOLOGY:

• The retrospective registry analysis included 447 adult patients with nonvalvular AFib, mean age 74 years, who were hospitalized with an ischemic stroke, 322 of whom were receiving direct oral anticoagulant (DOAC) therapy, mostly (84%) apixaban or rivaroxaban, and 125 were treated with left atrial appendage closure (LAAC), almost all (97%) with Watchman or Watchman-FLX devices.
• All patients received standard stroke care, monitoring, and treatment as well as physical therapy/rehabilitation.
• For the primary outcome, researchers used the modified Rankin Scale (mRS) to determine disabling (mRS score of 3-5) and fatal (mRS score of 6) strokes at discharge and at 3 months.
• The study adjusted for age, smoking, paroxysmal AFib, prior major bleeding, prior hemorrhagic stroke, medication adherence, and other risk factors.

TAKEAWAY:

• The incidence of disabling or fatal IS was significantly lower with LAAC versus with DOAC at discharge (38.3% vs. 70.3%; P < .001) and at 3 months (33.3% vs. 56.2%; P < .001), even though the LAAC group had more baseline comorbidity, for example, older age, more smokers, and more prior major bleeding.
• There was no significant difference in mortality between groups during hospitalization, but at 3 months, mortality was lower in the LAAC group (14.7% vs. 32.1%; P = .002).
• Multivariate linear regression analysis showed LAAC independently predicted more favorable mRS at discharge (2.8) and 3 months (1.4) (both P < .001) and was associated with less all-cause death at 3 months (odds ratio, 0.28; 95% confidence interval, 0.12-0.64; P = .002).
• Including those that excluded the 14.4% of LAAC patients who also received DOAC therapy, sensitivity analyses patients who got reduced dose DOACs and nonadherent patients yielded nearly identical outcomes to the full cohort analysis.

IN PRACTICE:

“Despite a higher baseline risk profile, patients treated with LAAC who developed IS had better outcomes than those receiving DOAC prophylaxis,” the authors conclude, adding that several ongoing prospective trials could, “shed light on the mechanism(s) responsible for differences in stroke severity.”

SOURCE:

The study was conducted by Mohit K. Turagam, MD, Icahn School of Medicine at Mount Sinai, New York, and colleagues. It was published online in JACC: Clinical Electrophysiology.

LIMITATIONS:

Despite sensitivity analyses and adjustment for risk factors, selection bias, missing data, and other confounding factors could have affected outcomes. The study didn’t evaluate recurrent IS or type and intensity of rehabilitation on outcomes. Lack of imaging data comparing stroke infarct size and volume limits understanding of exact mechanism driving higher stroke severity with DOACs. Because patients who died before reaching hospital weren’t captured in the registry, the actual mortality may be higher than reported.

DISCLOSURES:

Dr. Turagam has served as a consultant for Biosense Webster and Sanofi.

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

The American Heart Association (AHA) has unveiled a new heart disease risk calculator that aims to estimate an individual’s long-term risk for cardiovascular disease (CVD).

The new Predicting Risk of CVD Events (PREVENT) calculator is the first risk calculator that combines measures of cardiovascular, kidney, and metabolic health to estimate risk for CVD.

It follows an AHA presidential advisory and scientific statement published in October, formally defining cardiovascular-kidney-metabolic (CKM) syndrome.

The PREVENT calculator also “starts earlier and goes longer” than the pooled cohort equations (PCE), Sadiya Khan, MD, MSc, chair of the statement writing committee, told this news organization.

PREVENT is for use in adults aged 30-79 years and estimates the 10- and 30-year risk of total CVD including, for the first time, heart failure. The PCE were designed to assess 10-year risk of only myocardial infarction and stroke and only in adults aged 40-79 years.

“The new PREVENT equations are important for doctors because they allow us to start conversations earlier and more comprehensively and accurately calculate risk for our patients,” said Dr. Khan, preventive cardiologist at Northwestern Medicine and associate professor at Northwestern University in Chicago.

“We want to support clinicians in starting these conversations around optimizing CKM health earlier and begin to engage in discussions on ways to optimize health,” Dr. Khan added.

The AHA scientific statement on the PREVENT calculator, with Dr. Khan as lead author, was published online in Circulation, with an accompanying article that describes development and validation of the tool. 

Going beyond the PCE

The new calculator was developed using health information from more than 6 million adults from diverse racial and ethnic, socioeconomic, and geographic backgrounds.

In addition to blood pressure and cholesterol levels, the PREVENT equations allow for inclusion of hemoglobin A1c, if necessary, to monitor metabolic health.

It also includes estimated glomerular filtration rate (eGFR), a measure of kidney function, and allows for use of albumin excretion to monitor kidney disease to further individualize risk assessment and help inform personalized treatment options.

The new calculator also asks about tobacco use and use of medications for CVD risk factors and factors in age and sex, and it removes race from the risk calculations.

“The inclusion of race in risk prediction may imply that differences by race are not modifiable and may reify race as a biological construct, which may worsen health disparities. Therefore, it was decided a priori not to include race as a predictor in the development of PREVENT,” the writing group said.

They emphasized that the PREVENT calculator has similar accuracy among varied racial and ethnic groups.

The equations include an option to use the Social Deprivation Index, which incorporates measures of adverse social determinants of health such as education, poverty, unemployment, and factors based on a person’s environment.

The PREVENT equations are a “critical first step” toward including CKM health and social factors in risk prediction for CVD, Dr. Khan said in a news release.

“We are working on finalizing the online tool and it should be available soon – hopefully in a few weeks,” Dr. Khan told this news organization.
 

Knowledge gaps

The scientific statement lists several knowledge gaps and areas for more research. These include:

• Incorporating “net benefit” to identify the expected benefit of treatment recommendations based on an individual’s level of risk.
• Collecting more data from people of diverse race and ethnic backgrounds to better represent the increasing diversity in the United States. The number of Hispanic and Asian people included in the PREVENT datasets is lower than national estimates in the general U.S. population, so risk estimations in these populations may be less precise.
• Expanding the collection, reporting, and standardization of social determinants of health data, such as individual information rather than neighborhood information.
• Expanding risk assessment and prevention to earlier in life (childhood and/or adolescence) and in key life periods, such as during the peripartum period, since adverse pregnancy outcomes are associated with increased CVD risk.
• Investigating whether predicting adverse kidney outcomes, particularly among people with and without type 2 diabetes, may further optimize cardiovascular risk prediction.

The scientific statement was prepared by the volunteer writing group on behalf of the AHA. Dr. Khan reports no relevant financial relationships.

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

The American Heart Association (AHA) has unveiled a new heart disease risk calculator that aims to estimate an individual’s long-term risk for cardiovascular disease (CVD).

The new Predicting Risk of CVD Events (PREVENT) calculator is the first risk calculator that combines measures of cardiovascular, kidney, and metabolic health to estimate risk for CVD.

It follows an AHA presidential advisory and scientific statement published in October, formally defining cardiovascular-kidney-metabolic (CKM) syndrome.

The PREVENT calculator also “starts earlier and goes longer” than the pooled cohort equations (PCE), Sadiya Khan, MD, MSc, chair of the statement writing committee, told this news organization.

PREVENT is for use in adults aged 30-79 years and estimates the 10- and 30-year risk of total CVD including, for the first time, heart failure. The PCE were designed to assess 10-year risk of only myocardial infarction and stroke and only in adults aged 40-79 years.

“The new PREVENT equations are important for doctors because they allow us to start conversations earlier and more comprehensively and accurately calculate risk for our patients,” said Dr. Khan, preventive cardiologist at Northwestern Medicine and associate professor at Northwestern University in Chicago.

“We want to support clinicians in starting these conversations around optimizing CKM health earlier and begin to engage in discussions on ways to optimize health,” Dr. Khan added.

The AHA scientific statement on the PREVENT calculator, with Dr. Khan as lead author, was published online in Circulation, with an accompanying article that describes development and validation of the tool. 

Going beyond the PCE

The new calculator was developed using health information from more than 6 million adults from diverse racial and ethnic, socioeconomic, and geographic backgrounds.

In addition to blood pressure and cholesterol levels, the PREVENT equations allow for inclusion of hemoglobin A1c, if necessary, to monitor metabolic health.

It also includes estimated glomerular filtration rate (eGFR), a measure of kidney function, and allows for use of albumin excretion to monitor kidney disease to further individualize risk assessment and help inform personalized treatment options.

The new calculator also asks about tobacco use and use of medications for CVD risk factors and factors in age and sex, and it removes race from the risk calculations.

“The inclusion of race in risk prediction may imply that differences by race are not modifiable and may reify race as a biological construct, which may worsen health disparities. Therefore, it was decided a priori not to include race as a predictor in the development of PREVENT,” the writing group said.

They emphasized that the PREVENT calculator has similar accuracy among varied racial and ethnic groups.

The equations include an option to use the Social Deprivation Index, which incorporates measures of adverse social determinants of health such as education, poverty, unemployment, and factors based on a person’s environment.

The PREVENT equations are a “critical first step” toward including CKM health and social factors in risk prediction for CVD, Dr. Khan said in a news release.

“We are working on finalizing the online tool and it should be available soon – hopefully in a few weeks,” Dr. Khan told this news organization.
 

Knowledge gaps

The scientific statement lists several knowledge gaps and areas for more research. These include:

• Incorporating “net benefit” to identify the expected benefit of treatment recommendations based on an individual’s level of risk.
• Collecting more data from people of diverse race and ethnic backgrounds to better represent the increasing diversity in the United States. The number of Hispanic and Asian people included in the PREVENT datasets is lower than national estimates in the general U.S. population, so risk estimations in these populations may be less precise.
• Expanding the collection, reporting, and standardization of social determinants of health data, such as individual information rather than neighborhood information.
• Expanding risk assessment and prevention to earlier in life (childhood and/or adolescence) and in key life periods, such as during the peripartum period, since adverse pregnancy outcomes are associated with increased CVD risk.
• Investigating whether predicting adverse kidney outcomes, particularly among people with and without type 2 diabetes, may further optimize cardiovascular risk prediction.

The scientific statement was prepared by the volunteer writing group on behalf of the AHA. Dr. Khan reports no relevant financial relationships.

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

The American Heart Association (AHA) has unveiled a new heart disease risk calculator that aims to estimate an individual’s long-term risk for cardiovascular disease (CVD).

The new Predicting Risk of CVD Events (PREVENT) calculator is the first risk calculator that combines measures of cardiovascular, kidney, and metabolic health to estimate risk for CVD.

It follows an AHA presidential advisory and scientific statement published in October, formally defining cardiovascular-kidney-metabolic (CKM) syndrome.

The PREVENT calculator also “starts earlier and goes longer” than the pooled cohort equations (PCE), Sadiya Khan, MD, MSc, chair of the statement writing committee, told this news organization.

PREVENT is for use in adults aged 30-79 years and estimates the 10- and 30-year risk of total CVD including, for the first time, heart failure. The PCE were designed to assess 10-year risk of only myocardial infarction and stroke and only in adults aged 40-79 years.

“The new PREVENT equations are important for doctors because they allow us to start conversations earlier and more comprehensively and accurately calculate risk for our patients,” said Dr. Khan, preventive cardiologist at Northwestern Medicine and associate professor at Northwestern University in Chicago.

“We want to support clinicians in starting these conversations around optimizing CKM health earlier and begin to engage in discussions on ways to optimize health,” Dr. Khan added.

The AHA scientific statement on the PREVENT calculator, with Dr. Khan as lead author, was published online in Circulation, with an accompanying article that describes development and validation of the tool. 

Going beyond the PCE

The new calculator was developed using health information from more than 6 million adults from diverse racial and ethnic, socioeconomic, and geographic backgrounds.

In addition to blood pressure and cholesterol levels, the PREVENT equations allow for inclusion of hemoglobin A1c, if necessary, to monitor metabolic health.

It also includes estimated glomerular filtration rate (eGFR), a measure of kidney function, and allows for use of albumin excretion to monitor kidney disease to further individualize risk assessment and help inform personalized treatment options.

The new calculator also asks about tobacco use and use of medications for CVD risk factors and factors in age and sex, and it removes race from the risk calculations.

“The inclusion of race in risk prediction may imply that differences by race are not modifiable and may reify race as a biological construct, which may worsen health disparities. Therefore, it was decided a priori not to include race as a predictor in the development of PREVENT,” the writing group said.

They emphasized that the PREVENT calculator has similar accuracy among varied racial and ethnic groups.

The equations include an option to use the Social Deprivation Index, which incorporates measures of adverse social determinants of health such as education, poverty, unemployment, and factors based on a person’s environment.

The PREVENT equations are a “critical first step” toward including CKM health and social factors in risk prediction for CVD, Dr. Khan said in a news release.

“We are working on finalizing the online tool and it should be available soon – hopefully in a few weeks,” Dr. Khan told this news organization.
 

Knowledge gaps

The scientific statement lists several knowledge gaps and areas for more research. These include:

• Incorporating “net benefit” to identify the expected benefit of treatment recommendations based on an individual’s level of risk.
• Collecting more data from people of diverse race and ethnic backgrounds to better represent the increasing diversity in the United States. The number of Hispanic and Asian people included in the PREVENT datasets is lower than national estimates in the general U.S. population, so risk estimations in these populations may be less precise.
• Expanding the collection, reporting, and standardization of social determinants of health data, such as individual information rather than neighborhood information.
• Expanding risk assessment and prevention to earlier in life (childhood and/or adolescence) and in key life periods, such as during the peripartum period, since adverse pregnancy outcomes are associated with increased CVD risk.
• Investigating whether predicting adverse kidney outcomes, particularly among people with and without type 2 diabetes, may further optimize cardiovascular risk prediction.

The scientific statement was prepared by the volunteer writing group on behalf of the AHA. Dr. Khan reports no relevant financial relationships.

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