Cardiology

For smokers, deaths with a cardiovascular or cancer-related cause, or ones that can be attributed to a respiratory disease such as chronic obstructive pulmonary disease, are significantly more common than for nonsmokers. It is widely recognized that stopping smoking leads to a reduction in mortality risk. To make reliable statements on the timeline of this reduction, researchers analyzed interview data and death rates from 438,015 adult US citizens from 1997 to the end of 2019.

The analyses show that it takes 30 years for the mortality risk of ex-smokers to resemble that of people who never regularly smoked. Blake Thomson, PhD, and Fahrad Islami, MD, PhD, both members of the Department of Surveillance and Health Equity Science of the American Cancer Society in Atlanta, Georgia, published their results as a research letter in JAMA Internal Medicine.
 

After Smoking Cessation

Overall, 11,860 cardiovascular, 10,935 cancer-related, and 2,060 respiratory-related deaths were considered from over 5 million patient years. Taken from these figures, the mortality risks of continuous smokers were 2.3 times (cardiovascular), 3.4 times (cancer-related), and 13.3 times (respiratory-related) higher than those of continuous nonsmokers.

Within 10 years of stopping smoking, the following occurred:

• The cardiovascular mortality risk fell by 1.47 times, compared with nonsmokers (by 36% compared with smokers).
• The cancer-related mortality risk fell by 2.13 times, compared with nonsmokers (by 47% compared with smokers).
• The respiratory-related mortality risk fell by 6.35 times, compared with nonsmokers (by 43% compared with smokers).

In the second decade after stopping smoking, the risk dropped even further. The researchers observed the following trends:

• The cardiovascular mortality risk fell by 1.26 times.
• The cancer-related mortality risk fell by 1.59 times.
• The respiratory-related mortality risk fell by 3.63 times — each time compared with nonsmokers.

During the third decade after stopping smoking, the risk continued to decrease. The trends were as follows:

• The cardiovascular mortality risk fell by 1.07 times.
• The cancer-related mortality risk fell by 1.34 times.
• The respiratory-related mortality risk fell by 2.34 times, compared with nonsmokers.

30 Years Later

Only after more than 30 years of not smoking was the cardiovascular-related mortality risk 0.96 and, therefore, no longer significant. Compared with nonsmokers, the cancer-related mortality risk was 1.16, and the respiratory-related mortality risk was 1.31.

Therefore, former smokers can reduce their cardiovascular mortality risk by 100%, the cancer-related by 93%, and the respiratory-related mortality risk by 97%.

The result reinforces earlier analyses on the reduction in mortality risks by stopping smoking, with fewer participants. Smokers, therefore, benefit more the longer that they can refrain from using tobacco. “The earlier in life that smoking is given up, the better,” the authors wrote. But even in the first 10 years, the mortality risks examined decreased by a statistically significant 36% (cardiovascular) to 47% (cancer-related).
 

An Underestimation?

One disadvantage of the study is that the participants’ data were collected using personal questionnaires. For this reason, participants may have reported their tobacco consumption as being lower than it was, particularly because these questionnaires are often answered in hindsight, the authors pointed out.

In addition, some of the participants who reported stopping smoking completely may have only reduced their consumption. However, both circumstances would cause the results of the analysis to be even clearer, compared with reality, and therefore better.

This article was translated from the Medscape German edition.

A version of this article appeared on Medscape.com.

For smokers, deaths with a cardiovascular or cancer-related cause, or ones that can be attributed to a respiratory disease such as chronic obstructive pulmonary disease, are significantly more common than for nonsmokers. It is widely recognized that stopping smoking leads to a reduction in mortality risk. To make reliable statements on the timeline of this reduction, researchers analyzed interview data and death rates from 438,015 adult US citizens from 1997 to the end of 2019.

The analyses show that it takes 30 years for the mortality risk of ex-smokers to resemble that of people who never regularly smoked. Blake Thomson, PhD, and Fahrad Islami, MD, PhD, both members of the Department of Surveillance and Health Equity Science of the American Cancer Society in Atlanta, Georgia, published their results as a research letter in JAMA Internal Medicine.
 

After Smoking Cessation

Overall, 11,860 cardiovascular, 10,935 cancer-related, and 2,060 respiratory-related deaths were considered from over 5 million patient years. Taken from these figures, the mortality risks of continuous smokers were 2.3 times (cardiovascular), 3.4 times (cancer-related), and 13.3 times (respiratory-related) higher than those of continuous nonsmokers.

Within 10 years of stopping smoking, the following occurred:

• The cardiovascular mortality risk fell by 1.47 times, compared with nonsmokers (by 36% compared with smokers).
• The cancer-related mortality risk fell by 2.13 times, compared with nonsmokers (by 47% compared with smokers).
• The respiratory-related mortality risk fell by 6.35 times, compared with nonsmokers (by 43% compared with smokers).

In the second decade after stopping smoking, the risk dropped even further. The researchers observed the following trends:

• The cardiovascular mortality risk fell by 1.26 times.
• The cancer-related mortality risk fell by 1.59 times.
• The respiratory-related mortality risk fell by 3.63 times — each time compared with nonsmokers.

During the third decade after stopping smoking, the risk continued to decrease. The trends were as follows:

• The cardiovascular mortality risk fell by 1.07 times.
• The cancer-related mortality risk fell by 1.34 times.
• The respiratory-related mortality risk fell by 2.34 times, compared with nonsmokers.

30 Years Later

Only after more than 30 years of not smoking was the cardiovascular-related mortality risk 0.96 and, therefore, no longer significant. Compared with nonsmokers, the cancer-related mortality risk was 1.16, and the respiratory-related mortality risk was 1.31.

Therefore, former smokers can reduce their cardiovascular mortality risk by 100%, the cancer-related by 93%, and the respiratory-related mortality risk by 97%.

The result reinforces earlier analyses on the reduction in mortality risks by stopping smoking, with fewer participants. Smokers, therefore, benefit more the longer that they can refrain from using tobacco. “The earlier in life that smoking is given up, the better,” the authors wrote. But even in the first 10 years, the mortality risks examined decreased by a statistically significant 36% (cardiovascular) to 47% (cancer-related).
 

An Underestimation?

One disadvantage of the study is that the participants’ data were collected using personal questionnaires. For this reason, participants may have reported their tobacco consumption as being lower than it was, particularly because these questionnaires are often answered in hindsight, the authors pointed out.

In addition, some of the participants who reported stopping smoking completely may have only reduced their consumption. However, both circumstances would cause the results of the analysis to be even clearer, compared with reality, and therefore better.

This article was translated from the Medscape German edition.

A version of this article appeared on Medscape.com.

For smokers, deaths with a cardiovascular or cancer-related cause, or ones that can be attributed to a respiratory disease such as chronic obstructive pulmonary disease, are significantly more common than for nonsmokers. It is widely recognized that stopping smoking leads to a reduction in mortality risk. To make reliable statements on the timeline of this reduction, researchers analyzed interview data and death rates from 438,015 adult US citizens from 1997 to the end of 2019.

The analyses show that it takes 30 years for the mortality risk of ex-smokers to resemble that of people who never regularly smoked. Blake Thomson, PhD, and Fahrad Islami, MD, PhD, both members of the Department of Surveillance and Health Equity Science of the American Cancer Society in Atlanta, Georgia, published their results as a research letter in JAMA Internal Medicine.
 

After Smoking Cessation

Overall, 11,860 cardiovascular, 10,935 cancer-related, and 2,060 respiratory-related deaths were considered from over 5 million patient years. Taken from these figures, the mortality risks of continuous smokers were 2.3 times (cardiovascular), 3.4 times (cancer-related), and 13.3 times (respiratory-related) higher than those of continuous nonsmokers.

Within 10 years of stopping smoking, the following occurred:

• The cardiovascular mortality risk fell by 1.47 times, compared with nonsmokers (by 36% compared with smokers).
• The cancer-related mortality risk fell by 2.13 times, compared with nonsmokers (by 47% compared with smokers).
• The respiratory-related mortality risk fell by 6.35 times, compared with nonsmokers (by 43% compared with smokers).

In the second decade after stopping smoking, the risk dropped even further. The researchers observed the following trends:

• The cardiovascular mortality risk fell by 1.26 times.
• The cancer-related mortality risk fell by 1.59 times.
• The respiratory-related mortality risk fell by 3.63 times — each time compared with nonsmokers.

During the third decade after stopping smoking, the risk continued to decrease. The trends were as follows:

• The cardiovascular mortality risk fell by 1.07 times.
• The cancer-related mortality risk fell by 1.34 times.
• The respiratory-related mortality risk fell by 2.34 times, compared with nonsmokers.

30 Years Later

Only after more than 30 years of not smoking was the cardiovascular-related mortality risk 0.96 and, therefore, no longer significant. Compared with nonsmokers, the cancer-related mortality risk was 1.16, and the respiratory-related mortality risk was 1.31.

Therefore, former smokers can reduce their cardiovascular mortality risk by 100%, the cancer-related by 93%, and the respiratory-related mortality risk by 97%.

The result reinforces earlier analyses on the reduction in mortality risks by stopping smoking, with fewer participants. Smokers, therefore, benefit more the longer that they can refrain from using tobacco. “The earlier in life that smoking is given up, the better,” the authors wrote. But even in the first 10 years, the mortality risks examined decreased by a statistically significant 36% (cardiovascular) to 47% (cancer-related).
 

An Underestimation?

One disadvantage of the study is that the participants’ data were collected using personal questionnaires. For this reason, participants may have reported their tobacco consumption as being lower than it was, particularly because these questionnaires are often answered in hindsight, the authors pointed out.

In addition, some of the participants who reported stopping smoking completely may have only reduced their consumption. However, both circumstances would cause the results of the analysis to be even clearer, compared with reality, and therefore better.

This article was translated from the Medscape German edition.

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.

Systematically biased artificial intelligence (AI) models did not improve clinicians’ accuracy in diagnosing hospitalized patients, based on data from more than 450 clinicians.

“Artificial Intelligence (AI) could support clinicians in their diagnostic decisions of hospitalized patients but could also be biased and cause potential harm,” said Sarah Jabbour, MSE, a PhD candidate in computer science and engineering at the University of Michigan, Ann Arbor, in an interview.

“Regulatory guidance has suggested that the use of AI explanations could mitigate these harms, but the effectiveness of using AI explanations has not been established,” she said.

To examine whether AI explanations can be effective in mitigating the potential harms of systemic bias in AI models, Ms. Jabbour and colleagues conducted a randomized clinical vignette survey study. The survey was administered between April 2022 and January 2023 across 13 states, and the study population included hospitalist physicians, nurse practitioners, and physician assistants. The results were published in JAMA.

Participants were randomized to AI predictions with AI explanations (226 clinicians) or without AI explanations (231 clinicians).

The primary outcome was diagnostic accuracy for pneumonia, heart failure, and chronic obstructive pulmonary disease, defined as the number of correct diagnoses over the total number of assessments, the researchers wrote.

The clinicians viewed nine clinical vignettes of patients hospitalized with acute respiratory failure, including their presenting symptoms, physical examination, laboratory results, and chest radiographs. Clinicians viewed two vignettes with no AI model input to establish baseline diagnostic accuracy. They made three assessments in each vignette, one for each diagnosis. The order of the vignettes was two without AI predictions (to establish baseline diagnostic accuracy), six with AI predictions, and one with a clinical consultation by a hypothetical colleague. The vignettes included standard and systematically biased AI models.

The baseline diagnostic accuracy was 73% for the diagnoses of pneumonia, heart failure, and chronic obstructive pulmonary disease. Clinicians’ accuracy increased by 2.9% when they viewed a standard diagnostic AI model without explanations and by 4.4% when they viewed models with AI explanations.

However, clinicians’ accuracy decreased by 11.3% after viewing systematically biased AI model predictions without explanations compared with baseline, and biased AI model predictions with explanations decreased accuracy by 9.1%.

The decrease in accuracy with systematically biased AI predictions without explanations was mainly attributable to a decrease in the participants’ diagnostic specificity, the researchers noted, but the addition of explanations did little to improve it, the researchers said.

Potentially Useful but Still Imperfect

The findings were limited by several factors including the use of a web-based survey, which differs from surveys in a clinical setting, the researchers wrote. Other limitations included the younger than average study population, and the focus on the clinicians making treatment decisions, vs other clinicians who might have a better understanding of the AI explanations.

“In our study, explanations were presented in a way that were considered to be obvious, where the AI model was completely focused on areas of the chest X-rays unrelated to the clinical condition,” Ms. Jabbour told this news organization. “We hypothesized that if presented with such explanations, the participants in our study would notice that the model was behaving incorrectly and not rely on its predictions. This was surprisingly not the case, and the explanations when presented alongside biased AI predictions had seemingly no effect in mitigating clinicians’ overreliance on biased AI,” she said.

“AI is being developed at an extraordinary rate, and our study shows that it has the potential to improve clinical decision-making. At the same time, it could harm clinical decision-making when biased,” Ms. Jabbour said. “We must be thoughtful about how to carefully integrate AI into clinical workflows, with the goal of improving clinical care while not introducing systematic errors or harming patients,” she added.

Looking ahead, “There are several potential research areas that could be explored,” said Ms. Jabbour. “Researchers should focus on careful validation of AI models to identify biased model behavior prior to deployment. AI researchers should also continue including and communicating with clinicians during the development of AI tools to better understand clinicians’ needs and how they interact with AI,” she said. “This is not an exhaustive list of research directions, and it will take much discussion between experts across disciplines such as AI, human computer interaction, and medicine to ultimately deploy AI safely into clinical care.”

Don’t Overestimate AI

“With the increasing use of artificial intelligence and machine learning in other spheres, there has been an increase in interest in exploring how they can be utilized to improve clinical outcomes,” said Suman Pal, MD, assistant professor in the division of hospital medicine at the University of New Mexico, Albuquerque, in an interview. “However, concerns remain regarding the possible harms and ways to mitigate them,” said Dr. Pal, who was not involved in the current study.

In the current study, “It was interesting to note that explanations did not significantly mitigate the decrease in clinician accuracy from systematically biased AI model predictions,” Dr. Pal said.

“For the clinician, the findings of this study caution against overreliance on AI in clinical decision-making, especially because of the risk of exacerbating existing health disparities due to systemic inequities in existing literature,” Dr. Pal told this news organization.

“Additional research is needed to explore how clinicians can be better trained in identifying both the utility and the limitations of AI and into methods of validation and continuous quality checks with integration of AI into clinical workflows,” he noted.

The study was funded by the National Heart, Lung, and Blood Institute. The researchers had no financial conflicts to disclose. Dr. Pal had no financial conflicts to disclose.

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

Systematically biased artificial intelligence (AI) models did not improve clinicians’ accuracy in diagnosing hospitalized patients, based on data from more than 450 clinicians.

“Artificial Intelligence (AI) could support clinicians in their diagnostic decisions of hospitalized patients but could also be biased and cause potential harm,” said Sarah Jabbour, MSE, a PhD candidate in computer science and engineering at the University of Michigan, Ann Arbor, in an interview.

“Regulatory guidance has suggested that the use of AI explanations could mitigate these harms, but the effectiveness of using AI explanations has not been established,” she said.

To examine whether AI explanations can be effective in mitigating the potential harms of systemic bias in AI models, Ms. Jabbour and colleagues conducted a randomized clinical vignette survey study. The survey was administered between April 2022 and January 2023 across 13 states, and the study population included hospitalist physicians, nurse practitioners, and physician assistants. The results were published in JAMA.

Participants were randomized to AI predictions with AI explanations (226 clinicians) or without AI explanations (231 clinicians).

The primary outcome was diagnostic accuracy for pneumonia, heart failure, and chronic obstructive pulmonary disease, defined as the number of correct diagnoses over the total number of assessments, the researchers wrote.

The clinicians viewed nine clinical vignettes of patients hospitalized with acute respiratory failure, including their presenting symptoms, physical examination, laboratory results, and chest radiographs. Clinicians viewed two vignettes with no AI model input to establish baseline diagnostic accuracy. They made three assessments in each vignette, one for each diagnosis. The order of the vignettes was two without AI predictions (to establish baseline diagnostic accuracy), six with AI predictions, and one with a clinical consultation by a hypothetical colleague. The vignettes included standard and systematically biased AI models.

The baseline diagnostic accuracy was 73% for the diagnoses of pneumonia, heart failure, and chronic obstructive pulmonary disease. Clinicians’ accuracy increased by 2.9% when they viewed a standard diagnostic AI model without explanations and by 4.4% when they viewed models with AI explanations.

However, clinicians’ accuracy decreased by 11.3% after viewing systematically biased AI model predictions without explanations compared with baseline, and biased AI model predictions with explanations decreased accuracy by 9.1%.

The decrease in accuracy with systematically biased AI predictions without explanations was mainly attributable to a decrease in the participants’ diagnostic specificity, the researchers noted, but the addition of explanations did little to improve it, the researchers said.

Potentially Useful but Still Imperfect

The findings were limited by several factors including the use of a web-based survey, which differs from surveys in a clinical setting, the researchers wrote. Other limitations included the younger than average study population, and the focus on the clinicians making treatment decisions, vs other clinicians who might have a better understanding of the AI explanations.

“In our study, explanations were presented in a way that were considered to be obvious, where the AI model was completely focused on areas of the chest X-rays unrelated to the clinical condition,” Ms. Jabbour told this news organization. “We hypothesized that if presented with such explanations, the participants in our study would notice that the model was behaving incorrectly and not rely on its predictions. This was surprisingly not the case, and the explanations when presented alongside biased AI predictions had seemingly no effect in mitigating clinicians’ overreliance on biased AI,” she said.

“AI is being developed at an extraordinary rate, and our study shows that it has the potential to improve clinical decision-making. At the same time, it could harm clinical decision-making when biased,” Ms. Jabbour said. “We must be thoughtful about how to carefully integrate AI into clinical workflows, with the goal of improving clinical care while not introducing systematic errors or harming patients,” she added.

Looking ahead, “There are several potential research areas that could be explored,” said Ms. Jabbour. “Researchers should focus on careful validation of AI models to identify biased model behavior prior to deployment. AI researchers should also continue including and communicating with clinicians during the development of AI tools to better understand clinicians’ needs and how they interact with AI,” she said. “This is not an exhaustive list of research directions, and it will take much discussion between experts across disciplines such as AI, human computer interaction, and medicine to ultimately deploy AI safely into clinical care.”

Don’t Overestimate AI

“With the increasing use of artificial intelligence and machine learning in other spheres, there has been an increase in interest in exploring how they can be utilized to improve clinical outcomes,” said Suman Pal, MD, assistant professor in the division of hospital medicine at the University of New Mexico, Albuquerque, in an interview. “However, concerns remain regarding the possible harms and ways to mitigate them,” said Dr. Pal, who was not involved in the current study.

In the current study, “It was interesting to note that explanations did not significantly mitigate the decrease in clinician accuracy from systematically biased AI model predictions,” Dr. Pal said.

“For the clinician, the findings of this study caution against overreliance on AI in clinical decision-making, especially because of the risk of exacerbating existing health disparities due to systemic inequities in existing literature,” Dr. Pal told this news organization.

“Additional research is needed to explore how clinicians can be better trained in identifying both the utility and the limitations of AI and into methods of validation and continuous quality checks with integration of AI into clinical workflows,” he noted.

The study was funded by the National Heart, Lung, and Blood Institute. The researchers had no financial conflicts to disclose. Dr. Pal had no financial conflicts to disclose.

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

Systematically biased artificial intelligence (AI) models did not improve clinicians’ accuracy in diagnosing hospitalized patients, based on data from more than 450 clinicians.

“Artificial Intelligence (AI) could support clinicians in their diagnostic decisions of hospitalized patients but could also be biased and cause potential harm,” said Sarah Jabbour, MSE, a PhD candidate in computer science and engineering at the University of Michigan, Ann Arbor, in an interview.

“Regulatory guidance has suggested that the use of AI explanations could mitigate these harms, but the effectiveness of using AI explanations has not been established,” she said.

To examine whether AI explanations can be effective in mitigating the potential harms of systemic bias in AI models, Ms. Jabbour and colleagues conducted a randomized clinical vignette survey study. The survey was administered between April 2022 and January 2023 across 13 states, and the study population included hospitalist physicians, nurse practitioners, and physician assistants. The results were published in JAMA.

Participants were randomized to AI predictions with AI explanations (226 clinicians) or without AI explanations (231 clinicians).

The primary outcome was diagnostic accuracy for pneumonia, heart failure, and chronic obstructive pulmonary disease, defined as the number of correct diagnoses over the total number of assessments, the researchers wrote.

The clinicians viewed nine clinical vignettes of patients hospitalized with acute respiratory failure, including their presenting symptoms, physical examination, laboratory results, and chest radiographs. Clinicians viewed two vignettes with no AI model input to establish baseline diagnostic accuracy. They made three assessments in each vignette, one for each diagnosis. The order of the vignettes was two without AI predictions (to establish baseline diagnostic accuracy), six with AI predictions, and one with a clinical consultation by a hypothetical colleague. The vignettes included standard and systematically biased AI models.

The baseline diagnostic accuracy was 73% for the diagnoses of pneumonia, heart failure, and chronic obstructive pulmonary disease. Clinicians’ accuracy increased by 2.9% when they viewed a standard diagnostic AI model without explanations and by 4.4% when they viewed models with AI explanations.

However, clinicians’ accuracy decreased by 11.3% after viewing systematically biased AI model predictions without explanations compared with baseline, and biased AI model predictions with explanations decreased accuracy by 9.1%.

The decrease in accuracy with systematically biased AI predictions without explanations was mainly attributable to a decrease in the participants’ diagnostic specificity, the researchers noted, but the addition of explanations did little to improve it, the researchers said.

Potentially Useful but Still Imperfect

The findings were limited by several factors including the use of a web-based survey, which differs from surveys in a clinical setting, the researchers wrote. Other limitations included the younger than average study population, and the focus on the clinicians making treatment decisions, vs other clinicians who might have a better understanding of the AI explanations.

“In our study, explanations were presented in a way that were considered to be obvious, where the AI model was completely focused on areas of the chest X-rays unrelated to the clinical condition,” Ms. Jabbour told this news organization. “We hypothesized that if presented with such explanations, the participants in our study would notice that the model was behaving incorrectly and not rely on its predictions. This was surprisingly not the case, and the explanations when presented alongside biased AI predictions had seemingly no effect in mitigating clinicians’ overreliance on biased AI,” she said.

“AI is being developed at an extraordinary rate, and our study shows that it has the potential to improve clinical decision-making. At the same time, it could harm clinical decision-making when biased,” Ms. Jabbour said. “We must be thoughtful about how to carefully integrate AI into clinical workflows, with the goal of improving clinical care while not introducing systematic errors or harming patients,” she added.

Looking ahead, “There are several potential research areas that could be explored,” said Ms. Jabbour. “Researchers should focus on careful validation of AI models to identify biased model behavior prior to deployment. AI researchers should also continue including and communicating with clinicians during the development of AI tools to better understand clinicians’ needs and how they interact with AI,” she said. “This is not an exhaustive list of research directions, and it will take much discussion between experts across disciplines such as AI, human computer interaction, and medicine to ultimately deploy AI safely into clinical care.”

Don’t Overestimate AI

“With the increasing use of artificial intelligence and machine learning in other spheres, there has been an increase in interest in exploring how they can be utilized to improve clinical outcomes,” said Suman Pal, MD, assistant professor in the division of hospital medicine at the University of New Mexico, Albuquerque, in an interview. “However, concerns remain regarding the possible harms and ways to mitigate them,” said Dr. Pal, who was not involved in the current study.

In the current study, “It was interesting to note that explanations did not significantly mitigate the decrease in clinician accuracy from systematically biased AI model predictions,” Dr. Pal said.

“For the clinician, the findings of this study caution against overreliance on AI in clinical decision-making, especially because of the risk of exacerbating existing health disparities due to systemic inequities in existing literature,” Dr. Pal told this news organization.

“Additional research is needed to explore how clinicians can be better trained in identifying both the utility and the limitations of AI and into methods of validation and continuous quality checks with integration of AI into clinical workflows,” he noted.

The study was funded by the National Heart, Lung, and Blood Institute. The researchers had no financial conflicts to disclose. Dr. Pal had no financial conflicts to disclose.

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

Adults who used thiazide diuretics for hypertension were more likely than were those who used nonthiazide agents to develop hyponatremia within 2 years of starting treatment, a new study of more than 180,000 people has found.

Although thiazide diuretics generally are well-tolerated in the routine treatment of uncomplicated hypertension, severe adverse effects are possible, and their frequency has not been examined, according to Niklas Worm Andersson, MD, of Statens Serum Institut, in Copenhagen, Denmark, and his colleagues.

“Thiazide diuretics are commonly used drugs for the treatment of uncomplicated hypertension, and hyponatremia is a known potential side effect to thiazide treatment, but the frequency of this adverse event is inconsistently reported across drug labels,” Dr. Andersson told this news organization.

Product labels for thiazide diuretics list hyponatremia as a potential adverse event that can occur rarely (defined as a range from less than 1 in 10,000 to less than 1 in 100 individuals), but the extent of the burden is unclear given the wide range of symptoms of the condition, the researchers write. 

In a study published in Annals of Internal Medicine, Dr. Andersson and his colleagues reviewed data from population-based registries in Denmark of adults aged 40 years or older with uncomplicated hypertension, no recent prescriptions for antihypertensives, and no previous history of hyponatremia. They emulated two target trials. One trial compared the incidence of hyponatremia in new users of bendroflumethiazide (BFZ) vs a calcium-channel blocker (CCB). The other emulation compared the incidence of hyponatremia in new users of hydrochlorothiazide (HCTZ) plus a renin-angiotensin system (RAS) inhibitor vs a RAS inhibitor without HCTZ. 

The primary outcome was hyponatremia, defined as blood sodium < 130 mmol/L, within 2 years of starting treatment. 

The 2-year incidence of hyponatremia for the two thiazide diuretics was 3.83% for BFZ and 3.51% for HCTZ-RAS inhibitor. The risk difference in the incidence of hyponatremia was 1.35% for BFZ vs CCB and 1.38% for HCTZ-RAS inhibitor vs RAS inhibitor, the researchers reported. 

The study population included 37,786 new users of BFZ who were compared with 44,963 new users of CCBs as well as 11,943 new users of HCTZ-RAS inhibitors who were compared with 85,784 new users of RAS inhibitors only. 

Overall, older age and a greater number of comorbidities increased the cumulative hyponatremia in new users of thiazide-based hypertensives. The risk differences among individuals aged 80 years or older were 4.80% in the BFZ vs CCB study and 5.52% in the HCTZ-RAS inhibitor vs RAS inhibitor study. Among participants with three or more comorbidities, the risk differences in the two studies were 5.24% and 2.91%, respectively, Dr. Andersson’s group found.

The findings were limited by several factors, mainly the potential for confounding on the basis of the assumption that filled prescriptions equaled drug use, the researchers noted. Other limitations included the focus on new users and a Danish population only, which might limit generalizability, and a lack of data on blood pressure measures.

However, the results suggest a greater risk for hyponatremia with thiazide diuretics than what the drug labels indicate, especially early in treatment, the researchers concluded.

 

Data Reinforce Need for Vigilance in the Clinic

“Our findings highlight the continued need for clinical awareness and monitoring of this adverse drug reaction; particularly during the first months of treatment, in persons who are older or who have comorbidities,” Dr. Andersson told this news organization. “Further mapping of potential subpopulations at risk in terms of specific comorbidities is important to improve the prevention of this adverse event.”

“The thiazide diuretics have been recommended as first-line therapy for hypertension, and it was important to evaluate the potential development of hyponatremia, especially in the older patients given the potentially serious health effects caused by hyponatremia,” said Noel Deep, MD, a general internist in private practice in Antigo, Wisconsin. Dr. Deep, who was not involved in the study, also serves as chief medical officer and a staff physician at Aspirus Langlade Hospital in Antigo. 

The current study findings were not surprising, Dr. Deep added. “I have seen this occur in my patients, especially in the older female patients,” he said. “The results reinforce my practice of monitoring the electrolytes and renal function in 1-2 weeks after starting a thiazide diuretic, and then at regular intervals.”

In practice, clinicians should be aware of the potential development of hyponatremia and monitor and address the electrolyte abnormalities, Dr. Deep said. “While thiazide and thiazide-like diuretics are an important component of our treatment options for patients with hypertension and other conditions, we should also ensure that we are cognizant of and address the potential side effects or electrolyte imbalances caused by the medications.” 

The study was funded by the Independent Research Fund Denmark, Helsefonden, Dagmar Marshalls Fond, Gangstedfonden, A.P. Møller and Chastine Mc-Kinney Møller Foundation, Brødrene Hartmanns Fond, and Snedkermester Sophus Jacobsen og hustru Astrid Jacobsens Fond.

The researchers had no financial conflicts to disclose. Dr. Deep had no financial conflicts to disclose.

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

Adults who used thiazide diuretics for hypertension were more likely than were those who used nonthiazide agents to develop hyponatremia within 2 years of starting treatment, a new study of more than 180,000 people has found.

Although thiazide diuretics generally are well-tolerated in the routine treatment of uncomplicated hypertension, severe adverse effects are possible, and their frequency has not been examined, according to Niklas Worm Andersson, MD, of Statens Serum Institut, in Copenhagen, Denmark, and his colleagues.

“Thiazide diuretics are commonly used drugs for the treatment of uncomplicated hypertension, and hyponatremia is a known potential side effect to thiazide treatment, but the frequency of this adverse event is inconsistently reported across drug labels,” Dr. Andersson told this news organization.

Product labels for thiazide diuretics list hyponatremia as a potential adverse event that can occur rarely (defined as a range from less than 1 in 10,000 to less than 1 in 100 individuals), but the extent of the burden is unclear given the wide range of symptoms of the condition, the researchers write. 

In a study published in Annals of Internal Medicine, Dr. Andersson and his colleagues reviewed data from population-based registries in Denmark of adults aged 40 years or older with uncomplicated hypertension, no recent prescriptions for antihypertensives, and no previous history of hyponatremia. They emulated two target trials. One trial compared the incidence of hyponatremia in new users of bendroflumethiazide (BFZ) vs a calcium-channel blocker (CCB). The other emulation compared the incidence of hyponatremia in new users of hydrochlorothiazide (HCTZ) plus a renin-angiotensin system (RAS) inhibitor vs a RAS inhibitor without HCTZ. 

The primary outcome was hyponatremia, defined as blood sodium < 130 mmol/L, within 2 years of starting treatment. 

The 2-year incidence of hyponatremia for the two thiazide diuretics was 3.83% for BFZ and 3.51% for HCTZ-RAS inhibitor. The risk difference in the incidence of hyponatremia was 1.35% for BFZ vs CCB and 1.38% for HCTZ-RAS inhibitor vs RAS inhibitor, the researchers reported. 

The study population included 37,786 new users of BFZ who were compared with 44,963 new users of CCBs as well as 11,943 new users of HCTZ-RAS inhibitors who were compared with 85,784 new users of RAS inhibitors only. 

Overall, older age and a greater number of comorbidities increased the cumulative hyponatremia in new users of thiazide-based hypertensives. The risk differences among individuals aged 80 years or older were 4.80% in the BFZ vs CCB study and 5.52% in the HCTZ-RAS inhibitor vs RAS inhibitor study. Among participants with three or more comorbidities, the risk differences in the two studies were 5.24% and 2.91%, respectively, Dr. Andersson’s group found.

The findings were limited by several factors, mainly the potential for confounding on the basis of the assumption that filled prescriptions equaled drug use, the researchers noted. Other limitations included the focus on new users and a Danish population only, which might limit generalizability, and a lack of data on blood pressure measures.

However, the results suggest a greater risk for hyponatremia with thiazide diuretics than what the drug labels indicate, especially early in treatment, the researchers concluded.

 

Data Reinforce Need for Vigilance in the Clinic

“Our findings highlight the continued need for clinical awareness and monitoring of this adverse drug reaction; particularly during the first months of treatment, in persons who are older or who have comorbidities,” Dr. Andersson told this news organization. “Further mapping of potential subpopulations at risk in terms of specific comorbidities is important to improve the prevention of this adverse event.”

“The thiazide diuretics have been recommended as first-line therapy for hypertension, and it was important to evaluate the potential development of hyponatremia, especially in the older patients given the potentially serious health effects caused by hyponatremia,” said Noel Deep, MD, a general internist in private practice in Antigo, Wisconsin. Dr. Deep, who was not involved in the study, also serves as chief medical officer and a staff physician at Aspirus Langlade Hospital in Antigo. 

The current study findings were not surprising, Dr. Deep added. “I have seen this occur in my patients, especially in the older female patients,” he said. “The results reinforce my practice of monitoring the electrolytes and renal function in 1-2 weeks after starting a thiazide diuretic, and then at regular intervals.”

In practice, clinicians should be aware of the potential development of hyponatremia and monitor and address the electrolyte abnormalities, Dr. Deep said. “While thiazide and thiazide-like diuretics are an important component of our treatment options for patients with hypertension and other conditions, we should also ensure that we are cognizant of and address the potential side effects or electrolyte imbalances caused by the medications.” 

The study was funded by the Independent Research Fund Denmark, Helsefonden, Dagmar Marshalls Fond, Gangstedfonden, A.P. Møller and Chastine Mc-Kinney Møller Foundation, Brødrene Hartmanns Fond, and Snedkermester Sophus Jacobsen og hustru Astrid Jacobsens Fond.

The researchers had no financial conflicts to disclose. Dr. Deep had no financial conflicts to disclose.

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

Adults who used thiazide diuretics for hypertension were more likely than were those who used nonthiazide agents to develop hyponatremia within 2 years of starting treatment, a new study of more than 180,000 people has found.

Although thiazide diuretics generally are well-tolerated in the routine treatment of uncomplicated hypertension, severe adverse effects are possible, and their frequency has not been examined, according to Niklas Worm Andersson, MD, of Statens Serum Institut, in Copenhagen, Denmark, and his colleagues.

“Thiazide diuretics are commonly used drugs for the treatment of uncomplicated hypertension, and hyponatremia is a known potential side effect to thiazide treatment, but the frequency of this adverse event is inconsistently reported across drug labels,” Dr. Andersson told this news organization.

Product labels for thiazide diuretics list hyponatremia as a potential adverse event that can occur rarely (defined as a range from less than 1 in 10,000 to less than 1 in 100 individuals), but the extent of the burden is unclear given the wide range of symptoms of the condition, the researchers write. 

In a study published in Annals of Internal Medicine, Dr. Andersson and his colleagues reviewed data from population-based registries in Denmark of adults aged 40 years or older with uncomplicated hypertension, no recent prescriptions for antihypertensives, and no previous history of hyponatremia. They emulated two target trials. One trial compared the incidence of hyponatremia in new users of bendroflumethiazide (BFZ) vs a calcium-channel blocker (CCB). The other emulation compared the incidence of hyponatremia in new users of hydrochlorothiazide (HCTZ) plus a renin-angiotensin system (RAS) inhibitor vs a RAS inhibitor without HCTZ. 

The primary outcome was hyponatremia, defined as blood sodium < 130 mmol/L, within 2 years of starting treatment. 

The 2-year incidence of hyponatremia for the two thiazide diuretics was 3.83% for BFZ and 3.51% for HCTZ-RAS inhibitor. The risk difference in the incidence of hyponatremia was 1.35% for BFZ vs CCB and 1.38% for HCTZ-RAS inhibitor vs RAS inhibitor, the researchers reported. 

The study population included 37,786 new users of BFZ who were compared with 44,963 new users of CCBs as well as 11,943 new users of HCTZ-RAS inhibitors who were compared with 85,784 new users of RAS inhibitors only. 

Overall, older age and a greater number of comorbidities increased the cumulative hyponatremia in new users of thiazide-based hypertensives. The risk differences among individuals aged 80 years or older were 4.80% in the BFZ vs CCB study and 5.52% in the HCTZ-RAS inhibitor vs RAS inhibitor study. Among participants with three or more comorbidities, the risk differences in the two studies were 5.24% and 2.91%, respectively, Dr. Andersson’s group found.

The findings were limited by several factors, mainly the potential for confounding on the basis of the assumption that filled prescriptions equaled drug use, the researchers noted. Other limitations included the focus on new users and a Danish population only, which might limit generalizability, and a lack of data on blood pressure measures.

However, the results suggest a greater risk for hyponatremia with thiazide diuretics than what the drug labels indicate, especially early in treatment, the researchers concluded.

 

Data Reinforce Need for Vigilance in the Clinic

“Our findings highlight the continued need for clinical awareness and monitoring of this adverse drug reaction; particularly during the first months of treatment, in persons who are older or who have comorbidities,” Dr. Andersson told this news organization. “Further mapping of potential subpopulations at risk in terms of specific comorbidities is important to improve the prevention of this adverse event.”

“The thiazide diuretics have been recommended as first-line therapy for hypertension, and it was important to evaluate the potential development of hyponatremia, especially in the older patients given the potentially serious health effects caused by hyponatremia,” said Noel Deep, MD, a general internist in private practice in Antigo, Wisconsin. Dr. Deep, who was not involved in the study, also serves as chief medical officer and a staff physician at Aspirus Langlade Hospital in Antigo. 

The current study findings were not surprising, Dr. Deep added. “I have seen this occur in my patients, especially in the older female patients,” he said. “The results reinforce my practice of monitoring the electrolytes and renal function in 1-2 weeks after starting a thiazide diuretic, and then at regular intervals.”

In practice, clinicians should be aware of the potential development of hyponatremia and monitor and address the electrolyte abnormalities, Dr. Deep said. “While thiazide and thiazide-like diuretics are an important component of our treatment options for patients with hypertension and other conditions, we should also ensure that we are cognizant of and address the potential side effects or electrolyte imbalances caused by the medications.” 

The study was funded by the Independent Research Fund Denmark, Helsefonden, Dagmar Marshalls Fond, Gangstedfonden, A.P. Møller and Chastine Mc-Kinney Møller Foundation, Brødrene Hartmanns Fond, and Snedkermester Sophus Jacobsen og hustru Astrid Jacobsens Fond.

The researchers had no financial conflicts to disclose. Dr. Deep had no financial conflicts to disclose.

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

The relationship between alcohol consumption and cardiovascular disease (CVD) may be more nuanced than previously thought, with evidence emerging that alcohol use may both increase and decrease the risk for CVD.

The answer may depend on the presence of circulating metabolites of alcohol, some of which may be beneficial while others may be harmful, new research suggests. 

“We adopted an association analysis, looking at 60 metabolites produced during or after alcohol has been metabolized, to see whether those metabolites can link alcohol consumption with CVD,” senior author Jiantao Ma, PhD, MBBS, assistant professor, Division of Nutrition Epidemiology and Data Science, Friedman School, Tufts University, Boston, Massachusetts, said in an interview.

“We found that the relationship is quite complex, with some metabolites showing protective effects against CVD and others showing harmful effects,” said Dr. Ma. “This opens the door for future research because we think that these molecules can help [us] understand the mechanism of the relationship between alcohol and CVD.”

The study was published online in BMC Medicine.

J-Shaped Relationship?

Previous research has painted a confusing picture of the relationship between alcohol consumption and CVD. For example, some studies have suggested that moderate levels of drinking may be hazardous to cardiac health, while others have pointed to potential cardioprotective effects.

Nevertheless, “according to the latest ACC/AHA guidelines regarding alcohol consumption and its relationship to CVD, there is no level of alcohol use that is deemed safe and considered acceptable,” Saurabh Sharma, MD, program director, Internal Medicine Residency Program, and clinical assistant professor of cardiology, Geisinger Commonwealth School of Medicine, Scranton, Pennsylvania, said in an interview.

Older observational data suggested a “J-shaped” relationship between alcohol consumption and cardiovascular risk, such that a low to moderate amount might reduce risk, while higher amounts increase it, said Dr. Sharma, a member of the American College of Cardiology (ACC) Prevention of Cardiovascular Diseases Council.

“But it’s essential to note that these findings were based on observational studies. No randomized controlled trials have provided conclusive evidence supporting the idea that moderate alcohol consumption actively reduces cardiovascular risk,” he said.

The current study is also observational, but it shines a somewhat different spotlight on the subject by examining alcohol consumption–related metabolites, said Dr. Ma — that is, small molecules that are the intermediates or end-products of metabolism in many cellular processes. 

Some recent research “shows that alcohol may be harmful or at least has no beneficial effect in CVD prevention,” he said. “Our motivation was to analyze the association using metabolites, genetics, and epigenetics, because we think that these molecules may help us understand some of the mechanisms that underlie the relationship between alcohol consumption and CVD, and partially answer the question of whether alcohol may be harmful or helpful.” 

Caution Warranted

Although some previous studies have looked at metabolites, most analyzed alcohol consumption measured at a single time point, “which may not represent habitual or long-term alcohol consumption,” the researchers note. 

The team used data derived from 2458 Framingham Heart Study Offspring participants (mean age, 56 ± 9.3 years at the fifth examination; 52% female), calculating the cumulative average alcohol consumption from total intake of beer, wine, and liquor over an average 20-year period. Most participants were overweight, close to one fifth were current smokers, and 636 developed CVD over the study period.

Participants were assessed every 4-8 years, with metabolites measured during the fifth examination. 

Linear models were used to investigate the association of alcohol consumption with 211 plasma metabolites, adjusting for a variety of potential confounders, including age, sex, batch, smoking, diet, physical activity, body mass index, and familial relationship.

Sixty metabolites associated with cumulative average alcohol consumption were identified (P < .00024), after adjustment for confounders. Of these, 40 displayed positive associations with the cumulative average alcohol consumption, with the most significant metabolite being cholesteryl palmitoleate (CE16:1), a plasma cholesteryl ester involved with cholesterol metabolism.

One gram per day of higher alcohol consumption was associated with a higher-level CE16:1 in the blood (b = .023). Several other phosphatidylcholine metabolites were also positively associated with alcohol consumption.

On the other hand, 20 metabolites were negatively associated with alcohol consumption, with triacylglycerol 54:4 (TAG 54:4) displaying the most significant association (b = –.017).

The alcoholic beverages were not equal when it came to association with metabolites: 19 metabolites were significantly associated with the cumulative average consumption of beer, 30 with wine, and 32 with liquor. Seven were significantly associated with the cumulative consumption of all three types of drinks.

The researchers conducted survival analysis that identified 10 alcohol-associated metabolites associated with differential CVD risks, after adjusting for confounders. They also built two alcohol consumption–weighted metabolite scores using these 10 metabolites. After adjustment for confounders including CVD risk factors, the two scores had “comparable but opposite” associations with incident CVD, HR 1.11 (95% CI, 1.02-1.21) vs 0.88 (0.78-0.98; both P values = .02). 

“We found that seven metabolites were harmful, while three were beneficial, “ Dr. Ma reported. 

Dr. Ma cautioned that association “doesn’t represent causation.” On the basis of the findings, however, “we can hypothesize that if you drink a moderate amount of alcohol, you can either increase or decrease your risk of CVD.”

For people with cardiac conditions, “it would be [wise to be] cautious in recommending alcohol consumption,” he said. “For people without cardiac conditions, I would follow the recommendations of the AHA. If people don’t already drink alcohol, we don’t recommend that you start drinking it; and if you already drink, we’d recommend keeping it minimal.”

He cautioned that this is “only one study and we need more research if we are to generate a clearer message to the patient.” At present, perhaps the best message to patients is “to be cautious and warn them that there are potentially harmful effects,” he said.

Mendelian Randomization?

Dr. Sharma, who was not involved in the study, emphasized that it’s “crucial” to recognize that the study “does not alter the established understanding that any level of alcohol consumption poses harm to the heart,” and that “any amount of alcohol consumption has the potential to elevate triglyceride levels, thereby contributing to the increased risk of cardiovascular complications.”

Previously reported cardioprotective benefits “are likely influenced by confounding factors, such as lifestyle and sociodemographic elements,” he speculated. 

He noted that observational studies “encounter challenges in disentangling the influence of factors like obesity, lack of exercise, and tobacco use” as well as reverse causality.

“To overcome these limitations, Mendelian randomization emerges as a robust method,” he suggested. “This approach utilizes measured genetic variations with known functions to investigate the causal effect of a modifiable exposure on disease within the framework of observational studies.”

Notably, certain studies using this approach, including one by Larsson and colleagues, and another by Biddinger and associates, “have provided valuable insights by establishing a clear and causal relationship between alcohol consumption and CVD,” he said. 

The study was funded by the National Institute of Health’s National Institute on Alcohol Abuse and Alcoholism. Data collection in the Framingham Heart Study was supported by the National Heart, Lung, and Blood Institute. Dr. Ma and coauthors and Dr. Sharma disclosed no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

The relationship between alcohol consumption and cardiovascular disease (CVD) may be more nuanced than previously thought, with evidence emerging that alcohol use may both increase and decrease the risk for CVD.

The answer may depend on the presence of circulating metabolites of alcohol, some of which may be beneficial while others may be harmful, new research suggests. 

“We adopted an association analysis, looking at 60 metabolites produced during or after alcohol has been metabolized, to see whether those metabolites can link alcohol consumption with CVD,” senior author Jiantao Ma, PhD, MBBS, assistant professor, Division of Nutrition Epidemiology and Data Science, Friedman School, Tufts University, Boston, Massachusetts, said in an interview.

“We found that the relationship is quite complex, with some metabolites showing protective effects against CVD and others showing harmful effects,” said Dr. Ma. “This opens the door for future research because we think that these molecules can help [us] understand the mechanism of the relationship between alcohol and CVD.”

The study was published online in BMC Medicine.

J-Shaped Relationship?

Previous research has painted a confusing picture of the relationship between alcohol consumption and CVD. For example, some studies have suggested that moderate levels of drinking may be hazardous to cardiac health, while others have pointed to potential cardioprotective effects.

Nevertheless, “according to the latest ACC/AHA guidelines regarding alcohol consumption and its relationship to CVD, there is no level of alcohol use that is deemed safe and considered acceptable,” Saurabh Sharma, MD, program director, Internal Medicine Residency Program, and clinical assistant professor of cardiology, Geisinger Commonwealth School of Medicine, Scranton, Pennsylvania, said in an interview.

Older observational data suggested a “J-shaped” relationship between alcohol consumption and cardiovascular risk, such that a low to moderate amount might reduce risk, while higher amounts increase it, said Dr. Sharma, a member of the American College of Cardiology (ACC) Prevention of Cardiovascular Diseases Council.

“But it’s essential to note that these findings were based on observational studies. No randomized controlled trials have provided conclusive evidence supporting the idea that moderate alcohol consumption actively reduces cardiovascular risk,” he said.

The current study is also observational, but it shines a somewhat different spotlight on the subject by examining alcohol consumption–related metabolites, said Dr. Ma — that is, small molecules that are the intermediates or end-products of metabolism in many cellular processes. 

Some recent research “shows that alcohol may be harmful or at least has no beneficial effect in CVD prevention,” he said. “Our motivation was to analyze the association using metabolites, genetics, and epigenetics, because we think that these molecules may help us understand some of the mechanisms that underlie the relationship between alcohol consumption and CVD, and partially answer the question of whether alcohol may be harmful or helpful.” 

Caution Warranted

Although some previous studies have looked at metabolites, most analyzed alcohol consumption measured at a single time point, “which may not represent habitual or long-term alcohol consumption,” the researchers note. 

The team used data derived from 2458 Framingham Heart Study Offspring participants (mean age, 56 ± 9.3 years at the fifth examination; 52% female), calculating the cumulative average alcohol consumption from total intake of beer, wine, and liquor over an average 20-year period. Most participants were overweight, close to one fifth were current smokers, and 636 developed CVD over the study period.

Participants were assessed every 4-8 years, with metabolites measured during the fifth examination. 

Linear models were used to investigate the association of alcohol consumption with 211 plasma metabolites, adjusting for a variety of potential confounders, including age, sex, batch, smoking, diet, physical activity, body mass index, and familial relationship.

Sixty metabolites associated with cumulative average alcohol consumption were identified (P < .00024), after adjustment for confounders. Of these, 40 displayed positive associations with the cumulative average alcohol consumption, with the most significant metabolite being cholesteryl palmitoleate (CE16:1), a plasma cholesteryl ester involved with cholesterol metabolism.

One gram per day of higher alcohol consumption was associated with a higher-level CE16:1 in the blood (b = .023). Several other phosphatidylcholine metabolites were also positively associated with alcohol consumption.

On the other hand, 20 metabolites were negatively associated with alcohol consumption, with triacylglycerol 54:4 (TAG 54:4) displaying the most significant association (b = –.017).

The alcoholic beverages were not equal when it came to association with metabolites: 19 metabolites were significantly associated with the cumulative average consumption of beer, 30 with wine, and 32 with liquor. Seven were significantly associated with the cumulative consumption of all three types of drinks.

The researchers conducted survival analysis that identified 10 alcohol-associated metabolites associated with differential CVD risks, after adjusting for confounders. They also built two alcohol consumption–weighted metabolite scores using these 10 metabolites. After adjustment for confounders including CVD risk factors, the two scores had “comparable but opposite” associations with incident CVD, HR 1.11 (95% CI, 1.02-1.21) vs 0.88 (0.78-0.98; both P values = .02). 

“We found that seven metabolites were harmful, while three were beneficial, “ Dr. Ma reported. 

Dr. Ma cautioned that association “doesn’t represent causation.” On the basis of the findings, however, “we can hypothesize that if you drink a moderate amount of alcohol, you can either increase or decrease your risk of CVD.”

For people with cardiac conditions, “it would be [wise to be] cautious in recommending alcohol consumption,” he said. “For people without cardiac conditions, I would follow the recommendations of the AHA. If people don’t already drink alcohol, we don’t recommend that you start drinking it; and if you already drink, we’d recommend keeping it minimal.”

He cautioned that this is “only one study and we need more research if we are to generate a clearer message to the patient.” At present, perhaps the best message to patients is “to be cautious and warn them that there are potentially harmful effects,” he said.

Mendelian Randomization?

Dr. Sharma, who was not involved in the study, emphasized that it’s “crucial” to recognize that the study “does not alter the established understanding that any level of alcohol consumption poses harm to the heart,” and that “any amount of alcohol consumption has the potential to elevate triglyceride levels, thereby contributing to the increased risk of cardiovascular complications.”

Previously reported cardioprotective benefits “are likely influenced by confounding factors, such as lifestyle and sociodemographic elements,” he speculated. 

He noted that observational studies “encounter challenges in disentangling the influence of factors like obesity, lack of exercise, and tobacco use” as well as reverse causality.

“To overcome these limitations, Mendelian randomization emerges as a robust method,” he suggested. “This approach utilizes measured genetic variations with known functions to investigate the causal effect of a modifiable exposure on disease within the framework of observational studies.”

Notably, certain studies using this approach, including one by Larsson and colleagues, and another by Biddinger and associates, “have provided valuable insights by establishing a clear and causal relationship between alcohol consumption and CVD,” he said. 

The study was funded by the National Institute of Health’s National Institute on Alcohol Abuse and Alcoholism. Data collection in the Framingham Heart Study was supported by the National Heart, Lung, and Blood Institute. Dr. Ma and coauthors and Dr. Sharma disclosed no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

The relationship between alcohol consumption and cardiovascular disease (CVD) may be more nuanced than previously thought, with evidence emerging that alcohol use may both increase and decrease the risk for CVD.

The answer may depend on the presence of circulating metabolites of alcohol, some of which may be beneficial while others may be harmful, new research suggests. 

“We adopted an association analysis, looking at 60 metabolites produced during or after alcohol has been metabolized, to see whether those metabolites can link alcohol consumption with CVD,” senior author Jiantao Ma, PhD, MBBS, assistant professor, Division of Nutrition Epidemiology and Data Science, Friedman School, Tufts University, Boston, Massachusetts, said in an interview.

“We found that the relationship is quite complex, with some metabolites showing protective effects against CVD and others showing harmful effects,” said Dr. Ma. “This opens the door for future research because we think that these molecules can help [us] understand the mechanism of the relationship between alcohol and CVD.”

The study was published online in BMC Medicine.

J-Shaped Relationship?

Previous research has painted a confusing picture of the relationship between alcohol consumption and CVD. For example, some studies have suggested that moderate levels of drinking may be hazardous to cardiac health, while others have pointed to potential cardioprotective effects.

Nevertheless, “according to the latest ACC/AHA guidelines regarding alcohol consumption and its relationship to CVD, there is no level of alcohol use that is deemed safe and considered acceptable,” Saurabh Sharma, MD, program director, Internal Medicine Residency Program, and clinical assistant professor of cardiology, Geisinger Commonwealth School of Medicine, Scranton, Pennsylvania, said in an interview.

Older observational data suggested a “J-shaped” relationship between alcohol consumption and cardiovascular risk, such that a low to moderate amount might reduce risk, while higher amounts increase it, said Dr. Sharma, a member of the American College of Cardiology (ACC) Prevention of Cardiovascular Diseases Council.

“But it’s essential to note that these findings were based on observational studies. No randomized controlled trials have provided conclusive evidence supporting the idea that moderate alcohol consumption actively reduces cardiovascular risk,” he said.

The current study is also observational, but it shines a somewhat different spotlight on the subject by examining alcohol consumption–related metabolites, said Dr. Ma — that is, small molecules that are the intermediates or end-products of metabolism in many cellular processes. 

Some recent research “shows that alcohol may be harmful or at least has no beneficial effect in CVD prevention,” he said. “Our motivation was to analyze the association using metabolites, genetics, and epigenetics, because we think that these molecules may help us understand some of the mechanisms that underlie the relationship between alcohol consumption and CVD, and partially answer the question of whether alcohol may be harmful or helpful.” 

Caution Warranted

Although some previous studies have looked at metabolites, most analyzed alcohol consumption measured at a single time point, “which may not represent habitual or long-term alcohol consumption,” the researchers note. 

The team used data derived from 2458 Framingham Heart Study Offspring participants (mean age, 56 ± 9.3 years at the fifth examination; 52% female), calculating the cumulative average alcohol consumption from total intake of beer, wine, and liquor over an average 20-year period. Most participants were overweight, close to one fifth were current smokers, and 636 developed CVD over the study period.

Participants were assessed every 4-8 years, with metabolites measured during the fifth examination. 

Linear models were used to investigate the association of alcohol consumption with 211 plasma metabolites, adjusting for a variety of potential confounders, including age, sex, batch, smoking, diet, physical activity, body mass index, and familial relationship.

Sixty metabolites associated with cumulative average alcohol consumption were identified (P < .00024), after adjustment for confounders. Of these, 40 displayed positive associations with the cumulative average alcohol consumption, with the most significant metabolite being cholesteryl palmitoleate (CE16:1), a plasma cholesteryl ester involved with cholesterol metabolism.

One gram per day of higher alcohol consumption was associated with a higher-level CE16:1 in the blood (b = .023). Several other phosphatidylcholine metabolites were also positively associated with alcohol consumption.

On the other hand, 20 metabolites were negatively associated with alcohol consumption, with triacylglycerol 54:4 (TAG 54:4) displaying the most significant association (b = –.017).

The alcoholic beverages were not equal when it came to association with metabolites: 19 metabolites were significantly associated with the cumulative average consumption of beer, 30 with wine, and 32 with liquor. Seven were significantly associated with the cumulative consumption of all three types of drinks.

The researchers conducted survival analysis that identified 10 alcohol-associated metabolites associated with differential CVD risks, after adjusting for confounders. They also built two alcohol consumption–weighted metabolite scores using these 10 metabolites. After adjustment for confounders including CVD risk factors, the two scores had “comparable but opposite” associations with incident CVD, HR 1.11 (95% CI, 1.02-1.21) vs 0.88 (0.78-0.98; both P values = .02). 

“We found that seven metabolites were harmful, while three were beneficial, “ Dr. Ma reported. 

Dr. Ma cautioned that association “doesn’t represent causation.” On the basis of the findings, however, “we can hypothesize that if you drink a moderate amount of alcohol, you can either increase or decrease your risk of CVD.”

For people with cardiac conditions, “it would be [wise to be] cautious in recommending alcohol consumption,” he said. “For people without cardiac conditions, I would follow the recommendations of the AHA. If people don’t already drink alcohol, we don’t recommend that you start drinking it; and if you already drink, we’d recommend keeping it minimal.”

He cautioned that this is “only one study and we need more research if we are to generate a clearer message to the patient.” At present, perhaps the best message to patients is “to be cautious and warn them that there are potentially harmful effects,” he said.

Mendelian Randomization?

Dr. Sharma, who was not involved in the study, emphasized that it’s “crucial” to recognize that the study “does not alter the established understanding that any level of alcohol consumption poses harm to the heart,” and that “any amount of alcohol consumption has the potential to elevate triglyceride levels, thereby contributing to the increased risk of cardiovascular complications.”

Previously reported cardioprotective benefits “are likely influenced by confounding factors, such as lifestyle and sociodemographic elements,” he speculated. 

He noted that observational studies “encounter challenges in disentangling the influence of factors like obesity, lack of exercise, and tobacco use” as well as reverse causality.

“To overcome these limitations, Mendelian randomization emerges as a robust method,” he suggested. “This approach utilizes measured genetic variations with known functions to investigate the causal effect of a modifiable exposure on disease within the framework of observational studies.”

Notably, certain studies using this approach, including one by Larsson and colleagues, and another by Biddinger and associates, “have provided valuable insights by establishing a clear and causal relationship between alcohol consumption and CVD,” he said. 

The study was funded by the National Institute of Health’s National Institute on Alcohol Abuse and Alcoholism. Data collection in the Framingham Heart Study was supported by the National Heart, Lung, and Blood Institute. Dr. Ma and coauthors and Dr. Sharma disclosed no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

Use of pharmacomechanical catheter-directory thrombolysis significantly reduced the number of pulmonary artery branches with total or subtotal occlusions in patients with acute pulmonary embolism, based on data from more than 100 individuals.

Reduced distal vascular volume is a significant predictor of 30-day and 90-day mortality in acute pulmonary embolism (PE) patients, and pulmonary obstruction is often the cause, wrote Riyaz Bashir, MD, of Temple University, Philadelphia, Pennsylvania, and colleagues.

Some studies of catheter-based treatments have shown a reduction in pulmonary artery (PA) obstruction in PE patients, but the impact has been modest, the researchers said.

“The recently published RESCUE (Recombinant tPA by Endovascular Administration for the Treatment of Submassive PE Using CDT for the Reduction of Thrombus Burden) trial showed a 35.9% reduction in PA obstruction using the Refined Modified Miller Index (RMMI), the largest reduction of all published catheter studies with core lab measurement, with similar doses of tissue plasminogen activator (tPA),” the researchers wrote.

The Bashir endovascular catheter was designed to maximize thrombus reduction via a pharmacomechanical infusion. The catheter features an expandable basket of 6 nitinol-reinforced infusion limbs.

“There are three crucial goals that we want to accomplish in patients who have a severe pulmonary embolism,” Dr. Bashir said in an interview. “Those include, in the order of importance, survival, recovery of right ventricular function, and resolution of blocked pulmonary arteries; both segmental and proximal pulmonary arteries,” he said.

Most previous studies have focused on the first two goals, but they still need to evaluate the resolution of PA blockages carefully, said Dr. Bashir. “In our clinical practice, we have seen a large number of patients who develop debilitating shortness of breath from these blockages. We decided to carefully evaluate these blockages before and after pharmacomechanical catheter-directed thrombolysis with the Bashir endovascular catheter using the core lab data from the RESCUE study,” he said.

In the current study published in JACC: Advances), the researchers used baseline and 48-hour posttreatment contrast-enhanced chest computed tomography angiography of adult PE patients with right ventricular dilatation.

The study population included 107 adults with acute intermediate-risk PE who were treated with pharmacomechanical catheter-directory thrombolysis (PM-CDT) at 18 sites in the United States. Of these, 98 had intermediate high-risk PE with elevated troponin and/or brain-type natriuretic peptide (BNP) levels and 102 had bilateral PE.

The primary endpoint was the change in the number of segmental and proximal PA branches with total or subtotal occlusions (defined as > 65%) after 48 hours compared to baseline. Occlusions were assessed using McNemar’s test.

Patients with bilateral PE received two Bashir catheters; those with unilateral PE received one catheter each.

Each patient received a pulse spray of 2 mg of recombinant tPA (r-tPA) into each lung, followed by 5 mg of r-tPA over 5 hours; the total dose was 7 mg of r-tPA for patients with unilateral PEs and 14 mg for those with bilateral PEs, the researchers said. The median times for catheter placement and total procedure were 15 minutes and 54 minutes, respectively.

The number of segmental PA branches with total or subtotal occlusions decreased significantly, from 40.5% at baseline to 11.7% at 48 hours, and proximal PA branch total or subtotal occlusions decreased significantly, from 28.7% at baseline to 11.0% at 48 hours (P < 0.0001 for both).

The magnitude of the reductions in both total and subtotal occlusions of segmental arteries was significantly correlated with the extent of right ventricle recovery (measured by the reduction in right ventricular/left ventricular ratio) with a correlation coefficient of 0.287 (P = .0026); however, this correlation was not observed in the proximal PA arteries (correlation coefficient 0.132, P = .173).

One major bleeding event occurred within 72 hours in a patient who also experienced a device-related left common iliac vein thrombosis while not taking anticoagulation medication, and one death unrelated to PE occurred within 30 days.

“The two findings that surprised me include, first, a more than 70% reduction in total and subtotal occlusions in the segmental arteries with such a low dose of r-tPA and, second, the resolution of the blockages was seen not only in the arteries where the device was placed but also at remote sites away from the location of the catheter,” Dr. Bashir told this news organization.

The findings were limited by several factors including the lack of long-term clinical follow-up outcomes data and lack of comparison groups who underwent other treatments.

However, “This study implies that we now have a safe therapy for these patients that improves survival and right ventricular recovery in addition to dramatically improving blocked pulmonary arteries,” Dr. Bashir said.

As for additional research, “we need all the current and future prospective pulmonary embolism studies to include an assessment of pulmonary artery blockage resolution as an essential endpoint,” he said.
 

Catheter Expands Treatment Options

The current study, a subgroup analysis of the RESCUE trial, was one of the first to examine the impact of catheter-directed lysis on distal occlusions, study coauthor Parth M. Rali, MD, said in an interview.

To this point, literature has been limited to evaluation for proximal disease, said Dr. Rali, director of thoracic surgery and medicine and part of the Pulmonary Embolism Response Team at Temple University Hospital, Philadelphia.

Dr. Rali said he was encouraged to see confirmation that the BEC catheter, because of its design, works in patients with proximal or distal occlusive disease.

In clinical practice, “the catheter provides an additional option for care in patients with multiple distal occlusive disease when a systemic tissue plasminogen activator (tPA), may put patient at high bleeding risk,” Dr. Rali said.

Looking ahead, a prospective, observational multicenter study would be useful to validate the findings from the post hoc analysis of the current study, he noted.

The study was sponsored by the National Heart, Lung, and Blood Institute, Commonwealth of Pennsylvania, and Thrombolex Inc., a medical device company developing interventional catheter-based therapies for the rapid and effective treatment of acute venous thromboembolic disorders. Dr. Bashir is a cofounder and has an equity interest in Thrombolex Inc. Dr. Rali disclosed serving as a consultant for Thrombolex, Inari Medical, Viz AI, and ThinkSono.

Use of pharmacomechanical catheter-directory thrombolysis significantly reduced the number of pulmonary artery branches with total or subtotal occlusions in patients with acute pulmonary embolism, based on data from more than 100 individuals.

Reduced distal vascular volume is a significant predictor of 30-day and 90-day mortality in acute pulmonary embolism (PE) patients, and pulmonary obstruction is often the cause, wrote Riyaz Bashir, MD, of Temple University, Philadelphia, Pennsylvania, and colleagues.

Some studies of catheter-based treatments have shown a reduction in pulmonary artery (PA) obstruction in PE patients, but the impact has been modest, the researchers said.

“The recently published RESCUE (Recombinant tPA by Endovascular Administration for the Treatment of Submassive PE Using CDT for the Reduction of Thrombus Burden) trial showed a 35.9% reduction in PA obstruction using the Refined Modified Miller Index (RMMI), the largest reduction of all published catheter studies with core lab measurement, with similar doses of tissue plasminogen activator (tPA),” the researchers wrote.

The Bashir endovascular catheter was designed to maximize thrombus reduction via a pharmacomechanical infusion. The catheter features an expandable basket of 6 nitinol-reinforced infusion limbs.

“There are three crucial goals that we want to accomplish in patients who have a severe pulmonary embolism,” Dr. Bashir said in an interview. “Those include, in the order of importance, survival, recovery of right ventricular function, and resolution of blocked pulmonary arteries; both segmental and proximal pulmonary arteries,” he said.

Most previous studies have focused on the first two goals, but they still need to evaluate the resolution of PA blockages carefully, said Dr. Bashir. “In our clinical practice, we have seen a large number of patients who develop debilitating shortness of breath from these blockages. We decided to carefully evaluate these blockages before and after pharmacomechanical catheter-directed thrombolysis with the Bashir endovascular catheter using the core lab data from the RESCUE study,” he said.

In the current study published in JACC: Advances), the researchers used baseline and 48-hour posttreatment contrast-enhanced chest computed tomography angiography of adult PE patients with right ventricular dilatation.

The study population included 107 adults with acute intermediate-risk PE who were treated with pharmacomechanical catheter-directory thrombolysis (PM-CDT) at 18 sites in the United States. Of these, 98 had intermediate high-risk PE with elevated troponin and/or brain-type natriuretic peptide (BNP) levels and 102 had bilateral PE.

The primary endpoint was the change in the number of segmental and proximal PA branches with total or subtotal occlusions (defined as > 65%) after 48 hours compared to baseline. Occlusions were assessed using McNemar’s test.

Patients with bilateral PE received two Bashir catheters; those with unilateral PE received one catheter each.

Each patient received a pulse spray of 2 mg of recombinant tPA (r-tPA) into each lung, followed by 5 mg of r-tPA over 5 hours; the total dose was 7 mg of r-tPA for patients with unilateral PEs and 14 mg for those with bilateral PEs, the researchers said. The median times for catheter placement and total procedure were 15 minutes and 54 minutes, respectively.

The number of segmental PA branches with total or subtotal occlusions decreased significantly, from 40.5% at baseline to 11.7% at 48 hours, and proximal PA branch total or subtotal occlusions decreased significantly, from 28.7% at baseline to 11.0% at 48 hours (P < 0.0001 for both).

The magnitude of the reductions in both total and subtotal occlusions of segmental arteries was significantly correlated with the extent of right ventricle recovery (measured by the reduction in right ventricular/left ventricular ratio) with a correlation coefficient of 0.287 (P = .0026); however, this correlation was not observed in the proximal PA arteries (correlation coefficient 0.132, P = .173).

One major bleeding event occurred within 72 hours in a patient who also experienced a device-related left common iliac vein thrombosis while not taking anticoagulation medication, and one death unrelated to PE occurred within 30 days.

“The two findings that surprised me include, first, a more than 70% reduction in total and subtotal occlusions in the segmental arteries with such a low dose of r-tPA and, second, the resolution of the blockages was seen not only in the arteries where the device was placed but also at remote sites away from the location of the catheter,” Dr. Bashir told this news organization.

The findings were limited by several factors including the lack of long-term clinical follow-up outcomes data and lack of comparison groups who underwent other treatments.

However, “This study implies that we now have a safe therapy for these patients that improves survival and right ventricular recovery in addition to dramatically improving blocked pulmonary arteries,” Dr. Bashir said.

As for additional research, “we need all the current and future prospective pulmonary embolism studies to include an assessment of pulmonary artery blockage resolution as an essential endpoint,” he said.
 

Catheter Expands Treatment Options

The current study, a subgroup analysis of the RESCUE trial, was one of the first to examine the impact of catheter-directed lysis on distal occlusions, study coauthor Parth M. Rali, MD, said in an interview.

To this point, literature has been limited to evaluation for proximal disease, said Dr. Rali, director of thoracic surgery and medicine and part of the Pulmonary Embolism Response Team at Temple University Hospital, Philadelphia.

Dr. Rali said he was encouraged to see confirmation that the BEC catheter, because of its design, works in patients with proximal or distal occlusive disease.

In clinical practice, “the catheter provides an additional option for care in patients with multiple distal occlusive disease when a systemic tissue plasminogen activator (tPA), may put patient at high bleeding risk,” Dr. Rali said.

Looking ahead, a prospective, observational multicenter study would be useful to validate the findings from the post hoc analysis of the current study, he noted.

The study was sponsored by the National Heart, Lung, and Blood Institute, Commonwealth of Pennsylvania, and Thrombolex Inc., a medical device company developing interventional catheter-based therapies for the rapid and effective treatment of acute venous thromboembolic disorders. Dr. Bashir is a cofounder and has an equity interest in Thrombolex Inc. Dr. Rali disclosed serving as a consultant for Thrombolex, Inari Medical, Viz AI, and ThinkSono.

Use of pharmacomechanical catheter-directory thrombolysis significantly reduced the number of pulmonary artery branches with total or subtotal occlusions in patients with acute pulmonary embolism, based on data from more than 100 individuals.

Reduced distal vascular volume is a significant predictor of 30-day and 90-day mortality in acute pulmonary embolism (PE) patients, and pulmonary obstruction is often the cause, wrote Riyaz Bashir, MD, of Temple University, Philadelphia, Pennsylvania, and colleagues.

Some studies of catheter-based treatments have shown a reduction in pulmonary artery (PA) obstruction in PE patients, but the impact has been modest, the researchers said.

“The recently published RESCUE (Recombinant tPA by Endovascular Administration for the Treatment of Submassive PE Using CDT for the Reduction of Thrombus Burden) trial showed a 35.9% reduction in PA obstruction using the Refined Modified Miller Index (RMMI), the largest reduction of all published catheter studies with core lab measurement, with similar doses of tissue plasminogen activator (tPA),” the researchers wrote.

The Bashir endovascular catheter was designed to maximize thrombus reduction via a pharmacomechanical infusion. The catheter features an expandable basket of 6 nitinol-reinforced infusion limbs.

“There are three crucial goals that we want to accomplish in patients who have a severe pulmonary embolism,” Dr. Bashir said in an interview. “Those include, in the order of importance, survival, recovery of right ventricular function, and resolution of blocked pulmonary arteries; both segmental and proximal pulmonary arteries,” he said.

Most previous studies have focused on the first two goals, but they still need to evaluate the resolution of PA blockages carefully, said Dr. Bashir. “In our clinical practice, we have seen a large number of patients who develop debilitating shortness of breath from these blockages. We decided to carefully evaluate these blockages before and after pharmacomechanical catheter-directed thrombolysis with the Bashir endovascular catheter using the core lab data from the RESCUE study,” he said.

In the current study published in JACC: Advances), the researchers used baseline and 48-hour posttreatment contrast-enhanced chest computed tomography angiography of adult PE patients with right ventricular dilatation.

The study population included 107 adults with acute intermediate-risk PE who were treated with pharmacomechanical catheter-directory thrombolysis (PM-CDT) at 18 sites in the United States. Of these, 98 had intermediate high-risk PE with elevated troponin and/or brain-type natriuretic peptide (BNP) levels and 102 had bilateral PE.

The primary endpoint was the change in the number of segmental and proximal PA branches with total or subtotal occlusions (defined as > 65%) after 48 hours compared to baseline. Occlusions were assessed using McNemar’s test.

Patients with bilateral PE received two Bashir catheters; those with unilateral PE received one catheter each.

Each patient received a pulse spray of 2 mg of recombinant tPA (r-tPA) into each lung, followed by 5 mg of r-tPA over 5 hours; the total dose was 7 mg of r-tPA for patients with unilateral PEs and 14 mg for those with bilateral PEs, the researchers said. The median times for catheter placement and total procedure were 15 minutes and 54 minutes, respectively.

The number of segmental PA branches with total or subtotal occlusions decreased significantly, from 40.5% at baseline to 11.7% at 48 hours, and proximal PA branch total or subtotal occlusions decreased significantly, from 28.7% at baseline to 11.0% at 48 hours (P < 0.0001 for both).

The magnitude of the reductions in both total and subtotal occlusions of segmental arteries was significantly correlated with the extent of right ventricle recovery (measured by the reduction in right ventricular/left ventricular ratio) with a correlation coefficient of 0.287 (P = .0026); however, this correlation was not observed in the proximal PA arteries (correlation coefficient 0.132, P = .173).

One major bleeding event occurred within 72 hours in a patient who also experienced a device-related left common iliac vein thrombosis while not taking anticoagulation medication, and one death unrelated to PE occurred within 30 days.

“The two findings that surprised me include, first, a more than 70% reduction in total and subtotal occlusions in the segmental arteries with such a low dose of r-tPA and, second, the resolution of the blockages was seen not only in the arteries where the device was placed but also at remote sites away from the location of the catheter,” Dr. Bashir told this news organization.

The findings were limited by several factors including the lack of long-term clinical follow-up outcomes data and lack of comparison groups who underwent other treatments.

However, “This study implies that we now have a safe therapy for these patients that improves survival and right ventricular recovery in addition to dramatically improving blocked pulmonary arteries,” Dr. Bashir said.

As for additional research, “we need all the current and future prospective pulmonary embolism studies to include an assessment of pulmonary artery blockage resolution as an essential endpoint,” he said.
 

Catheter Expands Treatment Options

The current study, a subgroup analysis of the RESCUE trial, was one of the first to examine the impact of catheter-directed lysis on distal occlusions, study coauthor Parth M. Rali, MD, said in an interview.

To this point, literature has been limited to evaluation for proximal disease, said Dr. Rali, director of thoracic surgery and medicine and part of the Pulmonary Embolism Response Team at Temple University Hospital, Philadelphia.

Dr. Rali said he was encouraged to see confirmation that the BEC catheter, because of its design, works in patients with proximal or distal occlusive disease.

In clinical practice, “the catheter provides an additional option for care in patients with multiple distal occlusive disease when a systemic tissue plasminogen activator (tPA), may put patient at high bleeding risk,” Dr. Rali said.

Looking ahead, a prospective, observational multicenter study would be useful to validate the findings from the post hoc analysis of the current study, he noted.

The study was sponsored by the National Heart, Lung, and Blood Institute, Commonwealth of Pennsylvania, and Thrombolex Inc., a medical device company developing interventional catheter-based therapies for the rapid and effective treatment of acute venous thromboembolic disorders. Dr. Bashir is a cofounder and has an equity interest in Thrombolex Inc. Dr. Rali disclosed serving as a consultant for Thrombolex, Inari Medical, Viz AI, and ThinkSono.

A digital stethoscope that uses artificial intelligence (AI) is better at detecting heart murmurs associated with clinically significant valvular heart disease (VHD) than is a primary care physician (PCP) using a traditional stethoscope, a new study shows.

The results suggest collecting relevant sounds through a stethoscope (auscultation) using AI-powered technology is an important primary care tool to detect VHD, study author Moshe A. Rancier, MD, medical director, Massachusetts General Brigham Community Physicians, Lawrence, Massachusetts, said in an interview.

“Incorporating this AI-assisted device into the primary care exam will help identify patients at risk for VHD earlier and eventually decrease costs in our healthcare system,” he said, because timely detection could avoid emergency room visits and surgeries.

The findings were presented at the annual scientific sessions of the American Heart Association.
 

VHD Common

Clinically significant VHD, indicating structural damage to heart valves, affects 1 in 10 adults older than 65 years. Patients may be asymptomatic or present to their PCP with an unspecific symptom like fatigue or malaise.

If VHD is undiagnosed and left untreated, patients could develop more severe symptoms, even be at risk for death, and their quality of life is significantly affected, said Dr. Rancier.

Cardiac auscultation, the current point-of-care clinical standard, has relatively low sensitivity for detecting VHD, leaving most patients undiagnosed.

The deep learning–based AI tool uses sound data to detect cardiac murmurs associated with clinically significant VHD. The device used in the study (Eko; Eko Health) is approved by the US Food and Drug Administration and is on the market.

The tool identifies background sounds that might affect the evaluation. “If there’s any noise or breath sounds, it tells me this is not a good heart sound, and asks me to record again,” said Dr. Rancier.

A doctor using the AI-assisted stethoscope carries out the auscultation exam with the sound data captured by a smartphone or tablet and sent to the AI server. “I get an answer in a second as to if there’s a murmur or not,” said Dr. Rancier.

Not only that, but the tool can determine if it’s a systolic or diastolic murmur, he added.
 

Real-World Population

The study enrolled a “real-world” population of 368 patients, median age 70 years, 61% female, 70% White, and 18% Hispanic without a prior VHD diagnosis or history of murmur, from three primary care clinics in Queens, New York, and Lawrence and Haverhill, Massachusetts. 

About 79% of the cohort had hypertension, 68% had dyslipidemia, and 38% had diabetes, “which aligns with the population in the US,” said Dr. Rancier.

Each study participant had a regular exam carried out by Dr. Rancier using a traditional stethoscope to detect murmurs and an exam by a technician with a digital stethoscope that collected phonocardiogram (PCG) data for analysis by AI.

In addition, each patient received an echocardiogram 1-2 weeks later to confirm whether clinically significant VHD was present. An expert panel of cardiologists also reviewed the patient’s PCG recordings to confirm the presence of audible murmurs.

Dr. Rancier and the expert panel were blinded to AI and echocardiogram results.

Researchers calculated performance metrics for both PCP auscultation and the AI in detecting audible VHD.

The study showed that AI improved sensitivity to detect audible VHD by over twofold compared with PCP auscultation (94.1% vs 41.2%), with limited impact on specificity (84.5% vs 95.5%).

Dr. Rancier stressed the importance of sensitivity because clinicians tend to under-detect murmurs. “You don’t want to miss those patients because the consequences of undiagnosed VHD are dire.”

The AI tool identified 22 patients with moderate or greater VHD who were previously undiagnosed, whereas PCPs identified eight previously undiagnosed patients with VHD.

Dr. Rancier sees this tool being used beyond primary care, perhaps by emergency room personnel.

The authors plan to follow study participants and assess outcomes at for 6-12 months. They also aim to include more patients to increase the study’s power.
 

Expanding the Technology

They are also interested to see whether the technology can determine which valve is affected; for example, whether the issue is aortic stenosis or mitral regurgitation.

A limitation of the study was its small sample size.

Commenting on the findings, Dan Roden, MD, professor of medicine, pharmacology, and biomedical informatics, senior vice president for personalized medicine at Vanderbilt University Medical Center, Nashville, Tennessee, and chair of the American Heart Association Council on Genomic and Precision Medicine, noted that it demonstrated the AI-based stethoscope “did extraordinarily well” in predicting VHD. 

“I see this as an emerging technology — using an AI-enabled stethoscope and perhaps combining it with other imaging modalities, like an AI-enabled echocardiogram built into your stethoscope,” said Dr. Roden.

“Use of these new tools to detect the presence of valvular disease, as well as the extent of valvular disease and the extent of other kinds of heart disease, will likely help to transform CVD care.” 

The study was funded by Eko Health Inc. Dr. Rancier and Dr. Roden have no relevant conflicts of interest. 
 

A version of this article appeared on Medscape.com.

A digital stethoscope that uses artificial intelligence (AI) is better at detecting heart murmurs associated with clinically significant valvular heart disease (VHD) than is a primary care physician (PCP) using a traditional stethoscope, a new study shows.

The results suggest collecting relevant sounds through a stethoscope (auscultation) using AI-powered technology is an important primary care tool to detect VHD, study author Moshe A. Rancier, MD, medical director, Massachusetts General Brigham Community Physicians, Lawrence, Massachusetts, said in an interview.

“Incorporating this AI-assisted device into the primary care exam will help identify patients at risk for VHD earlier and eventually decrease costs in our healthcare system,” he said, because timely detection could avoid emergency room visits and surgeries.

The findings were presented at the annual scientific sessions of the American Heart Association.
 

VHD Common

Clinically significant VHD, indicating structural damage to heart valves, affects 1 in 10 adults older than 65 years. Patients may be asymptomatic or present to their PCP with an unspecific symptom like fatigue or malaise.

If VHD is undiagnosed and left untreated, patients could develop more severe symptoms, even be at risk for death, and their quality of life is significantly affected, said Dr. Rancier.

Cardiac auscultation, the current point-of-care clinical standard, has relatively low sensitivity for detecting VHD, leaving most patients undiagnosed.

The deep learning–based AI tool uses sound data to detect cardiac murmurs associated with clinically significant VHD. The device used in the study (Eko; Eko Health) is approved by the US Food and Drug Administration and is on the market.

The tool identifies background sounds that might affect the evaluation. “If there’s any noise or breath sounds, it tells me this is not a good heart sound, and asks me to record again,” said Dr. Rancier.

A doctor using the AI-assisted stethoscope carries out the auscultation exam with the sound data captured by a smartphone or tablet and sent to the AI server. “I get an answer in a second as to if there’s a murmur or not,” said Dr. Rancier.

Not only that, but the tool can determine if it’s a systolic or diastolic murmur, he added.
 

Real-World Population

The study enrolled a “real-world” population of 368 patients, median age 70 years, 61% female, 70% White, and 18% Hispanic without a prior VHD diagnosis or history of murmur, from three primary care clinics in Queens, New York, and Lawrence and Haverhill, Massachusetts. 

About 79% of the cohort had hypertension, 68% had dyslipidemia, and 38% had diabetes, “which aligns with the population in the US,” said Dr. Rancier.

Each study participant had a regular exam carried out by Dr. Rancier using a traditional stethoscope to detect murmurs and an exam by a technician with a digital stethoscope that collected phonocardiogram (PCG) data for analysis by AI.

In addition, each patient received an echocardiogram 1-2 weeks later to confirm whether clinically significant VHD was present. An expert panel of cardiologists also reviewed the patient’s PCG recordings to confirm the presence of audible murmurs.

Dr. Rancier and the expert panel were blinded to AI and echocardiogram results.

Researchers calculated performance metrics for both PCP auscultation and the AI in detecting audible VHD.

The study showed that AI improved sensitivity to detect audible VHD by over twofold compared with PCP auscultation (94.1% vs 41.2%), with limited impact on specificity (84.5% vs 95.5%).

Dr. Rancier stressed the importance of sensitivity because clinicians tend to under-detect murmurs. “You don’t want to miss those patients because the consequences of undiagnosed VHD are dire.”

The AI tool identified 22 patients with moderate or greater VHD who were previously undiagnosed, whereas PCPs identified eight previously undiagnosed patients with VHD.

Dr. Rancier sees this tool being used beyond primary care, perhaps by emergency room personnel.

The authors plan to follow study participants and assess outcomes at for 6-12 months. They also aim to include more patients to increase the study’s power.
 

Expanding the Technology

They are also interested to see whether the technology can determine which valve is affected; for example, whether the issue is aortic stenosis or mitral regurgitation.

A limitation of the study was its small sample size.

Commenting on the findings, Dan Roden, MD, professor of medicine, pharmacology, and biomedical informatics, senior vice president for personalized medicine at Vanderbilt University Medical Center, Nashville, Tennessee, and chair of the American Heart Association Council on Genomic and Precision Medicine, noted that it demonstrated the AI-based stethoscope “did extraordinarily well” in predicting VHD. 

“I see this as an emerging technology — using an AI-enabled stethoscope and perhaps combining it with other imaging modalities, like an AI-enabled echocardiogram built into your stethoscope,” said Dr. Roden.

“Use of these new tools to detect the presence of valvular disease, as well as the extent of valvular disease and the extent of other kinds of heart disease, will likely help to transform CVD care.” 

The study was funded by Eko Health Inc. Dr. Rancier and Dr. Roden have no relevant conflicts of interest. 
 

A version of this article appeared on Medscape.com.

A digital stethoscope that uses artificial intelligence (AI) is better at detecting heart murmurs associated with clinically significant valvular heart disease (VHD) than is a primary care physician (PCP) using a traditional stethoscope, a new study shows.

The results suggest collecting relevant sounds through a stethoscope (auscultation) using AI-powered technology is an important primary care tool to detect VHD, study author Moshe A. Rancier, MD, medical director, Massachusetts General Brigham Community Physicians, Lawrence, Massachusetts, said in an interview.

“Incorporating this AI-assisted device into the primary care exam will help identify patients at risk for VHD earlier and eventually decrease costs in our healthcare system,” he said, because timely detection could avoid emergency room visits and surgeries.

The findings were presented at the annual scientific sessions of the American Heart Association.
 

VHD Common

Clinically significant VHD, indicating structural damage to heart valves, affects 1 in 10 adults older than 65 years. Patients may be asymptomatic or present to their PCP with an unspecific symptom like fatigue or malaise.

If VHD is undiagnosed and left untreated, patients could develop more severe symptoms, even be at risk for death, and their quality of life is significantly affected, said Dr. Rancier.

Cardiac auscultation, the current point-of-care clinical standard, has relatively low sensitivity for detecting VHD, leaving most patients undiagnosed.

The deep learning–based AI tool uses sound data to detect cardiac murmurs associated with clinically significant VHD. The device used in the study (Eko; Eko Health) is approved by the US Food and Drug Administration and is on the market.

The tool identifies background sounds that might affect the evaluation. “If there’s any noise or breath sounds, it tells me this is not a good heart sound, and asks me to record again,” said Dr. Rancier.

A doctor using the AI-assisted stethoscope carries out the auscultation exam with the sound data captured by a smartphone or tablet and sent to the AI server. “I get an answer in a second as to if there’s a murmur or not,” said Dr. Rancier.

Not only that, but the tool can determine if it’s a systolic or diastolic murmur, he added.
 

Real-World Population

The study enrolled a “real-world” population of 368 patients, median age 70 years, 61% female, 70% White, and 18% Hispanic without a prior VHD diagnosis or history of murmur, from three primary care clinics in Queens, New York, and Lawrence and Haverhill, Massachusetts. 

About 79% of the cohort had hypertension, 68% had dyslipidemia, and 38% had diabetes, “which aligns with the population in the US,” said Dr. Rancier.

Each study participant had a regular exam carried out by Dr. Rancier using a traditional stethoscope to detect murmurs and an exam by a technician with a digital stethoscope that collected phonocardiogram (PCG) data for analysis by AI.

In addition, each patient received an echocardiogram 1-2 weeks later to confirm whether clinically significant VHD was present. An expert panel of cardiologists also reviewed the patient’s PCG recordings to confirm the presence of audible murmurs.

Dr. Rancier and the expert panel were blinded to AI and echocardiogram results.

Researchers calculated performance metrics for both PCP auscultation and the AI in detecting audible VHD.

The study showed that AI improved sensitivity to detect audible VHD by over twofold compared with PCP auscultation (94.1% vs 41.2%), with limited impact on specificity (84.5% vs 95.5%).

Dr. Rancier stressed the importance of sensitivity because clinicians tend to under-detect murmurs. “You don’t want to miss those patients because the consequences of undiagnosed VHD are dire.”

The AI tool identified 22 patients with moderate or greater VHD who were previously undiagnosed, whereas PCPs identified eight previously undiagnosed patients with VHD.

Dr. Rancier sees this tool being used beyond primary care, perhaps by emergency room personnel.

The authors plan to follow study participants and assess outcomes at for 6-12 months. They also aim to include more patients to increase the study’s power.
 

Expanding the Technology

They are also interested to see whether the technology can determine which valve is affected; for example, whether the issue is aortic stenosis or mitral regurgitation.

A limitation of the study was its small sample size.

Commenting on the findings, Dan Roden, MD, professor of medicine, pharmacology, and biomedical informatics, senior vice president for personalized medicine at Vanderbilt University Medical Center, Nashville, Tennessee, and chair of the American Heart Association Council on Genomic and Precision Medicine, noted that it demonstrated the AI-based stethoscope “did extraordinarily well” in predicting VHD. 

“I see this as an emerging technology — using an AI-enabled stethoscope and perhaps combining it with other imaging modalities, like an AI-enabled echocardiogram built into your stethoscope,” said Dr. Roden.

“Use of these new tools to detect the presence of valvular disease, as well as the extent of valvular disease and the extent of other kinds of heart disease, will likely help to transform CVD care.” 

The study was funded by Eko Health Inc. Dr. Rancier and Dr. Roden have no relevant conflicts of interest. 
 

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.

In a new report, the Midwest Institute for Clinical and Economic Review’s (ICER) Comparative Effectiveness Public Advisory Council concluded that the Merck drug sotatercept, currently under review by the US Food and Drug Administration (FDA), has a high certainty of at least a small net health benefit to patients with pulmonary arterial hypertension (PAH) when added to background therapy. The limited availability of evidence means that the benefit could range from minimal to substantial, according to the authors. 

Sotatercept, administered by injection every 3 weeks, is a first-in-class activin signaling inhibitor. It counters cell proliferation and decreases inflammation in vessel walls, which may lead to improved pulmonary blood flow. The US FDA is considering it for approval through a biologics license application, with a decision expected by March 26, 2024.

There remains a great deal of uncertainty surrounding the long-term benefits of sotatercept. It’s possible that the drug is disease-modifying, but there isn’t yet any proof, according to Greg Curfman, MD, who attended a virtual ICER public meeting on December 1 that summarized the report and accepted public comments. “I’m still wondering the extent to which disease-modifying issue here is more aspirational at this point than really documented,” said Dr. Curfman, who is an associated professor of medicine at Harvard Medical School and executive editor of the Journal of the American Medical Association.

Current PAH treatment consists of vasodilators, including phosphodiesterase-5 inhibitors (PDE5i), guanylate cyclase stimulators, endothelin receptor antagonists (ERA), prostacyclin analogues (prostanoids), and a prostacyclin receptor agonist. The 2022 European Society of Cardiology and the European Respiratory Society clinical practice guideline recommends that low- and intermediate-risk patients should be started on ERA/PDE5i combination therapy, while high-risk patients should also be given an intravenous or subcutaneous prostacyclin analogue, referred to as triple therapy.

Sotatercept’s regulatory approval hinges on the phase 3 STELLAR trial, which included 323 patients with World Health Organization functional class (WHO-FC) II and III PAH who were randomized to 0.75 mg/kg sotatercept in addition to background double or triple therapy, or background therapy alone. The mean age was 48 years, and the mean time since diagnosis was 8.8 years. About 40% received infused prostacyclin therapy at baseline. At 24 weeks, the median change in 6-min walking distance (6mWD) was 40.8 m longer in the sotatercept group. More patients in the sotatercept group experienced WHO-FC improvement (29.4% vs 13.8%). Those in the sotatercept group also experienced an 84% reduction in risk for clinical worsening or death. PAH-specific quality of life scales did not show a difference between the two groups. Open-label extension trials have shown that benefits are maintained for up to 2 years. Adverse events likely related to sotatercept included telangiectasias, increased hemoglobin levels, and bleeding events.

Along with its benefits, the report authors suggest that the subcutaneous delivery of sotatercept may be less burdensome to patients than some other PAH treatments, especially inhaled and intravenous prostanoids. “However, uncertainty remains about sotatercept’s efficacy in sicker populations and in those with connective tissue disease, and about the durability of effect,” the authors wrote.

A lack of long-term data leaves open the question of its effect on mortality and unknown adverse effects.

Using a de novo decision analytic model, the authors estimated that sotatercept treatment would lead to a longer time without symptoms at rest and more quality-adjusted life years, life years, and equal value life years. They determined the health benefit price benchmark for sotatercept to be between $18,700 and $36,200 per year. “The long-term conventional cost-effectiveness of sotatercept is largely dependent on the long-term effect of sotatercept on improving functional class and slowing the worsening in functional class; however, controlled trial evidence for sotatercept is limited to 24 weeks. Long-term data are necessary to reduce the uncertainty in sotatercept’s long-term effect on improving functional class and slowing the worsening in functional class,” the authors wrote. 

During the online meeting, Dr. Curfman took note of the fact that the STELLAR trial reported a median value of increase in 6mWD, rather than a mean, and the 40-m improvement is close to the value accepted as clinically meaningful. “So that tells us that half the patients had less than a clinically important improvement in the six-minute walk distance. We should be putting that in perspective,” said Dr. Curfman.

Another attendee pointed out that the open-label PULSAR extension trial showed that the proportion of patients in the sotatercept arm who were functional class I rose from 7.5% at the end of the trial to 20.6% at the end of the open-label period and wondered if that could be a sign of disease-modifying activity. “I think that’s a remarkable piece of data. I don’t recall seeing that in any other open label [trial of a PAH therapy] — that much of an improvement in getting to our best functional status,” said Marc Simon, MD, professor of medicine and director of the Pulmonary Hypertension Center at the University of California, San Francisco, who was a coauthor of the report.

Dr. Curfman has no relevant financial disclosures. Dr. Simon has consulted for Merck.

A version of this article appeared on Medscape.com.

In a new report, the Midwest Institute for Clinical and Economic Review’s (ICER) Comparative Effectiveness Public Advisory Council concluded that the Merck drug sotatercept, currently under review by the US Food and Drug Administration (FDA), has a high certainty of at least a small net health benefit to patients with pulmonary arterial hypertension (PAH) when added to background therapy. The limited availability of evidence means that the benefit could range from minimal to substantial, according to the authors. 

Sotatercept, administered by injection every 3 weeks, is a first-in-class activin signaling inhibitor. It counters cell proliferation and decreases inflammation in vessel walls, which may lead to improved pulmonary blood flow. The US FDA is considering it for approval through a biologics license application, with a decision expected by March 26, 2024.

There remains a great deal of uncertainty surrounding the long-term benefits of sotatercept. It’s possible that the drug is disease-modifying, but there isn’t yet any proof, according to Greg Curfman, MD, who attended a virtual ICER public meeting on December 1 that summarized the report and accepted public comments. “I’m still wondering the extent to which disease-modifying issue here is more aspirational at this point than really documented,” said Dr. Curfman, who is an associated professor of medicine at Harvard Medical School and executive editor of the Journal of the American Medical Association.

Current PAH treatment consists of vasodilators, including phosphodiesterase-5 inhibitors (PDE5i), guanylate cyclase stimulators, endothelin receptor antagonists (ERA), prostacyclin analogues (prostanoids), and a prostacyclin receptor agonist. The 2022 European Society of Cardiology and the European Respiratory Society clinical practice guideline recommends that low- and intermediate-risk patients should be started on ERA/PDE5i combination therapy, while high-risk patients should also be given an intravenous or subcutaneous prostacyclin analogue, referred to as triple therapy.

Sotatercept’s regulatory approval hinges on the phase 3 STELLAR trial, which included 323 patients with World Health Organization functional class (WHO-FC) II and III PAH who were randomized to 0.75 mg/kg sotatercept in addition to background double or triple therapy, or background therapy alone. The mean age was 48 years, and the mean time since diagnosis was 8.8 years. About 40% received infused prostacyclin therapy at baseline. At 24 weeks, the median change in 6-min walking distance (6mWD) was 40.8 m longer in the sotatercept group. More patients in the sotatercept group experienced WHO-FC improvement (29.4% vs 13.8%). Those in the sotatercept group also experienced an 84% reduction in risk for clinical worsening or death. PAH-specific quality of life scales did not show a difference between the two groups. Open-label extension trials have shown that benefits are maintained for up to 2 years. Adverse events likely related to sotatercept included telangiectasias, increased hemoglobin levels, and bleeding events.

Along with its benefits, the report authors suggest that the subcutaneous delivery of sotatercept may be less burdensome to patients than some other PAH treatments, especially inhaled and intravenous prostanoids. “However, uncertainty remains about sotatercept’s efficacy in sicker populations and in those with connective tissue disease, and about the durability of effect,” the authors wrote.

A lack of long-term data leaves open the question of its effect on mortality and unknown adverse effects.

Using a de novo decision analytic model, the authors estimated that sotatercept treatment would lead to a longer time without symptoms at rest and more quality-adjusted life years, life years, and equal value life years. They determined the health benefit price benchmark for sotatercept to be between $18,700 and $36,200 per year. “The long-term conventional cost-effectiveness of sotatercept is largely dependent on the long-term effect of sotatercept on improving functional class and slowing the worsening in functional class; however, controlled trial evidence for sotatercept is limited to 24 weeks. Long-term data are necessary to reduce the uncertainty in sotatercept’s long-term effect on improving functional class and slowing the worsening in functional class,” the authors wrote. 

During the online meeting, Dr. Curfman took note of the fact that the STELLAR trial reported a median value of increase in 6mWD, rather than a mean, and the 40-m improvement is close to the value accepted as clinically meaningful. “So that tells us that half the patients had less than a clinically important improvement in the six-minute walk distance. We should be putting that in perspective,” said Dr. Curfman.

Another attendee pointed out that the open-label PULSAR extension trial showed that the proportion of patients in the sotatercept arm who were functional class I rose from 7.5% at the end of the trial to 20.6% at the end of the open-label period and wondered if that could be a sign of disease-modifying activity. “I think that’s a remarkable piece of data. I don’t recall seeing that in any other open label [trial of a PAH therapy] — that much of an improvement in getting to our best functional status,” said Marc Simon, MD, professor of medicine and director of the Pulmonary Hypertension Center at the University of California, San Francisco, who was a coauthor of the report.

Dr. Curfman has no relevant financial disclosures. Dr. Simon has consulted for Merck.

A version of this article appeared on Medscape.com.

In a new report, the Midwest Institute for Clinical and Economic Review’s (ICER) Comparative Effectiveness Public Advisory Council concluded that the Merck drug sotatercept, currently under review by the US Food and Drug Administration (FDA), has a high certainty of at least a small net health benefit to patients with pulmonary arterial hypertension (PAH) when added to background therapy. The limited availability of evidence means that the benefit could range from minimal to substantial, according to the authors. 

Sotatercept, administered by injection every 3 weeks, is a first-in-class activin signaling inhibitor. It counters cell proliferation and decreases inflammation in vessel walls, which may lead to improved pulmonary blood flow. The US FDA is considering it for approval through a biologics license application, with a decision expected by March 26, 2024.

There remains a great deal of uncertainty surrounding the long-term benefits of sotatercept. It’s possible that the drug is disease-modifying, but there isn’t yet any proof, according to Greg Curfman, MD, who attended a virtual ICER public meeting on December 1 that summarized the report and accepted public comments. “I’m still wondering the extent to which disease-modifying issue here is more aspirational at this point than really documented,” said Dr. Curfman, who is an associated professor of medicine at Harvard Medical School and executive editor of the Journal of the American Medical Association.

Current PAH treatment consists of vasodilators, including phosphodiesterase-5 inhibitors (PDE5i), guanylate cyclase stimulators, endothelin receptor antagonists (ERA), prostacyclin analogues (prostanoids), and a prostacyclin receptor agonist. The 2022 European Society of Cardiology and the European Respiratory Society clinical practice guideline recommends that low- and intermediate-risk patients should be started on ERA/PDE5i combination therapy, while high-risk patients should also be given an intravenous or subcutaneous prostacyclin analogue, referred to as triple therapy.

Sotatercept’s regulatory approval hinges on the phase 3 STELLAR trial, which included 323 patients with World Health Organization functional class (WHO-FC) II and III PAH who were randomized to 0.75 mg/kg sotatercept in addition to background double or triple therapy, or background therapy alone. The mean age was 48 years, and the mean time since diagnosis was 8.8 years. About 40% received infused prostacyclin therapy at baseline. At 24 weeks, the median change in 6-min walking distance (6mWD) was 40.8 m longer in the sotatercept group. More patients in the sotatercept group experienced WHO-FC improvement (29.4% vs 13.8%). Those in the sotatercept group also experienced an 84% reduction in risk for clinical worsening or death. PAH-specific quality of life scales did not show a difference between the two groups. Open-label extension trials have shown that benefits are maintained for up to 2 years. Adverse events likely related to sotatercept included telangiectasias, increased hemoglobin levels, and bleeding events.

Along with its benefits, the report authors suggest that the subcutaneous delivery of sotatercept may be less burdensome to patients than some other PAH treatments, especially inhaled and intravenous prostanoids. “However, uncertainty remains about sotatercept’s efficacy in sicker populations and in those with connective tissue disease, and about the durability of effect,” the authors wrote.

A lack of long-term data leaves open the question of its effect on mortality and unknown adverse effects.

Using a de novo decision analytic model, the authors estimated that sotatercept treatment would lead to a longer time without symptoms at rest and more quality-adjusted life years, life years, and equal value life years. They determined the health benefit price benchmark for sotatercept to be between $18,700 and $36,200 per year. “The long-term conventional cost-effectiveness of sotatercept is largely dependent on the long-term effect of sotatercept on improving functional class and slowing the worsening in functional class; however, controlled trial evidence for sotatercept is limited to 24 weeks. Long-term data are necessary to reduce the uncertainty in sotatercept’s long-term effect on improving functional class and slowing the worsening in functional class,” the authors wrote. 

During the online meeting, Dr. Curfman took note of the fact that the STELLAR trial reported a median value of increase in 6mWD, rather than a mean, and the 40-m improvement is close to the value accepted as clinically meaningful. “So that tells us that half the patients had less than a clinically important improvement in the six-minute walk distance. We should be putting that in perspective,” said Dr. Curfman.

Another attendee pointed out that the open-label PULSAR extension trial showed that the proportion of patients in the sotatercept arm who were functional class I rose from 7.5% at the end of the trial to 20.6% at the end of the open-label period and wondered if that could be a sign of disease-modifying activity. “I think that’s a remarkable piece of data. I don’t recall seeing that in any other open label [trial of a PAH therapy] — that much of an improvement in getting to our best functional status,” said Marc Simon, MD, professor of medicine and director of the Pulmonary Hypertension Center at the University of California, San Francisco, who was a coauthor of the report.

Dr. Curfman has no relevant financial disclosures. Dr. Simon has consulted for Merck.

A version of this article appeared on Medscape.com.

TOPLINE:

Adults diagnosed with coronary heart disease (CHD) are at an increased risk for dementia, including all-cause dementia, Alzheimer›s disease (AD), and vascular dementia (VD), with the risk highest — at 36% — if onset is before age 45, results of a large observational study show.

METHODOLOGY:

• The study included 432,667 of the more than 500,000 participants in the UK Biobank, with a mean age of 56.9 years, 50,685 (11.7%) of whom had CHD and 50,445 had data on age at CHD onset.
• Researchers divided participants into three groups according to age at CHD onset (below 45 years, 45-59 years, and 60 years and older), and carried out a propensity score matching analysis.
• Outcomes included all-cause dementia, AD, and VD.
• Covariates included age, sex, race, educational level, body mass index, low-density lipoprotein cholesterol, smoking status, alcohol intake, exercise, depressed mood, hypertension, diabetes, statin use, and apolipoprotein E4 status.

TAKEAWAY:

• During a median follow-up of 12.8 years, researchers identified 5876 cases of all-cause dementia, 2540 cases of AD, and 1220 cases of VD.
• Fully adjusted models showed participants with CHD had significantly higher risks than those without CHD of developing all-cause dementia (hazard ratio [HR], 1.36; 95% CI, 1.28-1.45; P < .001), AD (HR, 1.13; 95% CI, 1.02-1.24; P = .019), and VD (HR, 1.78; 95% CI, 1.56-2.02; P < .001). The higher risk for VD suggests CHD has a more profound influence on neuropathologic changes involved in this dementia type, said the authors.
• Those with CHD diagnosed at a younger age had higher risks of developing dementia (HR per 10-year decrease in age, 1.25; 95% CI, 1.20-1.30 for all-cause dementia, 1.29; 95% CI, 1.20-1.38 for AD, and 1.22; 95% CI, 1.13-1.31 for VD; P for all < .001).
• Propensity score matching analysis showed patients with CHD had significantly higher risks for dementia compared with matched controls, with the highest risk seen in patients diagnosed before age 45 (HR, 2.40; 95% CI, 1.79-3.20; P < .001), followed by those diagnosed between 45 and 59 years (HR, 1.46; 95% CI, 1.32-1.62; P < .001) and at or above 60 years (HR, 1.11; 95% CI, 1.03-1.19; P = .005), with similar results for AD and VD.

IN PRACTICE:

The findings suggest “additional attention should be paid to the cognitive status of patients with CHD, especially the ones diagnosed with CHD at a young age,” the authors conclude, noting that “timely intervention, such as cognitive training, could be implemented once signs of cognitive deteriorations are detected.”

SOURCE:

The study was conducted by Jie Liang, BS, School of Nursing, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, and colleagues. It was published online on November 29, 2023, in the Journal of the American Heart Association.

LIMITATIONS:

As this is an observational study, it can’t conclude a causal relationship. Although the authors adjusted for many potential confounders, unknown risk factors that also contribute to CHD can’t be ruled out. As the study excluded 69,744 participants, selection bias is possible. The study included a mostly White population.

DISCLOSURES:

The study was supported by the National Natural Science Foundation of China, the Non-Profit Central Research Institute Fund of the Chinese Academy of Medical Sciences, and the China Medical Board. The authors have no relevant conflicts of interest.

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

TOPLINE:

Adults diagnosed with coronary heart disease (CHD) are at an increased risk for dementia, including all-cause dementia, Alzheimer›s disease (AD), and vascular dementia (VD), with the risk highest — at 36% — if onset is before age 45, results of a large observational study show.

METHODOLOGY:

• The study included 432,667 of the more than 500,000 participants in the UK Biobank, with a mean age of 56.9 years, 50,685 (11.7%) of whom had CHD and 50,445 had data on age at CHD onset.
• Researchers divided participants into three groups according to age at CHD onset (below 45 years, 45-59 years, and 60 years and older), and carried out a propensity score matching analysis.
• Outcomes included all-cause dementia, AD, and VD.
• Covariates included age, sex, race, educational level, body mass index, low-density lipoprotein cholesterol, smoking status, alcohol intake, exercise, depressed mood, hypertension, diabetes, statin use, and apolipoprotein E4 status.

TAKEAWAY:

• During a median follow-up of 12.8 years, researchers identified 5876 cases of all-cause dementia, 2540 cases of AD, and 1220 cases of VD.
• Fully adjusted models showed participants with CHD had significantly higher risks than those without CHD of developing all-cause dementia (hazard ratio [HR], 1.36; 95% CI, 1.28-1.45; P < .001), AD (HR, 1.13; 95% CI, 1.02-1.24; P = .019), and VD (HR, 1.78; 95% CI, 1.56-2.02; P < .001). The higher risk for VD suggests CHD has a more profound influence on neuropathologic changes involved in this dementia type, said the authors.
• Those with CHD diagnosed at a younger age had higher risks of developing dementia (HR per 10-year decrease in age, 1.25; 95% CI, 1.20-1.30 for all-cause dementia, 1.29; 95% CI, 1.20-1.38 for AD, and 1.22; 95% CI, 1.13-1.31 for VD; P for all < .001).
• Propensity score matching analysis showed patients with CHD had significantly higher risks for dementia compared with matched controls, with the highest risk seen in patients diagnosed before age 45 (HR, 2.40; 95% CI, 1.79-3.20; P < .001), followed by those diagnosed between 45 and 59 years (HR, 1.46; 95% CI, 1.32-1.62; P < .001) and at or above 60 years (HR, 1.11; 95% CI, 1.03-1.19; P = .005), with similar results for AD and VD.

IN PRACTICE:

The findings suggest “additional attention should be paid to the cognitive status of patients with CHD, especially the ones diagnosed with CHD at a young age,” the authors conclude, noting that “timely intervention, such as cognitive training, could be implemented once signs of cognitive deteriorations are detected.”

SOURCE:

The study was conducted by Jie Liang, BS, School of Nursing, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, and colleagues. It was published online on November 29, 2023, in the Journal of the American Heart Association.

LIMITATIONS:

As this is an observational study, it can’t conclude a causal relationship. Although the authors adjusted for many potential confounders, unknown risk factors that also contribute to CHD can’t be ruled out. As the study excluded 69,744 participants, selection bias is possible. The study included a mostly White population.

DISCLOSURES:

The study was supported by the National Natural Science Foundation of China, the Non-Profit Central Research Institute Fund of the Chinese Academy of Medical Sciences, and the China Medical Board. The authors have no relevant conflicts of interest.

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

TOPLINE:

Adults diagnosed with coronary heart disease (CHD) are at an increased risk for dementia, including all-cause dementia, Alzheimer›s disease (AD), and vascular dementia (VD), with the risk highest — at 36% — if onset is before age 45, results of a large observational study show.

METHODOLOGY:

• The study included 432,667 of the more than 500,000 participants in the UK Biobank, with a mean age of 56.9 years, 50,685 (11.7%) of whom had CHD and 50,445 had data on age at CHD onset.
• Researchers divided participants into three groups according to age at CHD onset (below 45 years, 45-59 years, and 60 years and older), and carried out a propensity score matching analysis.
• Outcomes included all-cause dementia, AD, and VD.
• Covariates included age, sex, race, educational level, body mass index, low-density lipoprotein cholesterol, smoking status, alcohol intake, exercise, depressed mood, hypertension, diabetes, statin use, and apolipoprotein E4 status.

TAKEAWAY:

• During a median follow-up of 12.8 years, researchers identified 5876 cases of all-cause dementia, 2540 cases of AD, and 1220 cases of VD.
• Fully adjusted models showed participants with CHD had significantly higher risks than those without CHD of developing all-cause dementia (hazard ratio [HR], 1.36; 95% CI, 1.28-1.45; P < .001), AD (HR, 1.13; 95% CI, 1.02-1.24; P = .019), and VD (HR, 1.78; 95% CI, 1.56-2.02; P < .001). The higher risk for VD suggests CHD has a more profound influence on neuropathologic changes involved in this dementia type, said the authors.
• Those with CHD diagnosed at a younger age had higher risks of developing dementia (HR per 10-year decrease in age, 1.25; 95% CI, 1.20-1.30 for all-cause dementia, 1.29; 95% CI, 1.20-1.38 for AD, and 1.22; 95% CI, 1.13-1.31 for VD; P for all < .001).
• Propensity score matching analysis showed patients with CHD had significantly higher risks for dementia compared with matched controls, with the highest risk seen in patients diagnosed before age 45 (HR, 2.40; 95% CI, 1.79-3.20; P < .001), followed by those diagnosed between 45 and 59 years (HR, 1.46; 95% CI, 1.32-1.62; P < .001) and at or above 60 years (HR, 1.11; 95% CI, 1.03-1.19; P = .005), with similar results for AD and VD.

IN PRACTICE:

The findings suggest “additional attention should be paid to the cognitive status of patients with CHD, especially the ones diagnosed with CHD at a young age,” the authors conclude, noting that “timely intervention, such as cognitive training, could be implemented once signs of cognitive deteriorations are detected.”

SOURCE:

The study was conducted by Jie Liang, BS, School of Nursing, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, and colleagues. It was published online on November 29, 2023, in the Journal of the American Heart Association.

LIMITATIONS:

As this is an observational study, it can’t conclude a causal relationship. Although the authors adjusted for many potential confounders, unknown risk factors that also contribute to CHD can’t be ruled out. As the study excluded 69,744 participants, selection bias is possible. The study included a mostly White population.

DISCLOSURES:

The study was supported by the National Natural Science Foundation of China, the Non-Profit Central Research Institute Fund of the Chinese Academy of Medical Sciences, and the China Medical Board. The authors have no relevant conflicts of interest.

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