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Forty-five circulating proteins in plasma are linked to the risk for myocardial infarction (MI), showed a new study that confirms some known associations and identifies new ones. Several proteins are associated with MI in women but not men, and some proteins linked with MI in both men and women are more strongly associated with MI in women.

“We hope that our study will shed light on pathways in MI,” said principal author Olga Titova, PhD, an epidemiologist at Uppsala University in Uppsala, Sweden. The work was published in the European Heart Journal.

Martha Gulati, MD, a cardiologist and associate director of the Barbra Streisand Women’s Heart Center at Cedars-Sinai Medical Center in Los Angeles and coauthor of an accompanying editorial, said the novel discovery of different patterns between men and women makes this an exciting study. The findings “highlight that sex differences in disease phenotype begin at the molecular level,” she said.

Titova and her team analyzed thousands of patients in two databases — one in Sweden (11,751 patients), the other in the United Kingdom (51,613 patients) — to discover proteins in the patients who went on to have an MI. Using one database to discover biomarkers and a second to replicate the findings is a common approach, said Titova.

Casting a Wide Net to Catch Proteins

The two databases “make findings more generalizable, allow us to confirm robust associations, and help minimize the risk of false positives.” The two databases mean researchers are more confident that the findings can be applied across populations, Titova added.

A total of 44 proteins were associated with later MI in both databases, adjusted for common MI risk factors as well as such factors as education, diet, physical activity, and alcohol intake, Titova explained. An additional protein was included from the first database that was unavailable in the second. Some of the proteins have been found in other studies, and this study confirms the link. Others were new, and a few appear to protect patients from MI.

“Most of the proteins are related to or involved in inflammation and atherosclerosis,” said Titova.

This is the first study to cast such a wide net, Titova pointed out. While several proteins have previously been linked to MI, most earlier studies have focused on specific proteins in populations that already have coronary artery disease or have involved cohorts of men only.

But she stresses that this study poses more questions than it answers. More research is needed to determine how proteins are involved in pathways leading to MI. The study found that some proteins may be mediators of general cardiovascular disease risk, whereas others are involved in mechanisms specifically linked to MI. Many proteins are involved in atherosclerosis, thrombosis, inflammation, immune system–related pathways, injury and tissue repair, coagulation, bone homeostasis, and iron metabolism.

“At this point, some [proteins] appear to be causal, some seem to be an association,” said Titova. It remains to be determined “which are on the causal path, which are potential biomarkers, which are going to shed light on the mechanisms” of MI.

The study took a step toward determining which proteins might be involved in causing MI through an analysis of some protein levels determined by genetics. This found three proteins linked to a higher risk for MI and three linked to a lower risk.

It’s Different for Women

Thirteen of the proteins were linked with later MI in women, either exclusively or more strongly than in men. Many of these associations were replicated in the second database, showing an alignment across populations.

Titova said the reason for the sex difference remains a mystery. “We have to go to the molecular level. It could be a consequence of risk factors affecting the sexes differently or different biology” between men and women.

Gulati, who specializes in women’s heart health, explained, “We know inflammation is much more prevalent in women and is the pathway to cardiovascular disease.” She points out that noncardiac inflammatory diseases are also more prevalent in women. Other biomarkers for inflammation, such as C-reactive protein, are higher in women than in men. She thinks the underlying mechanisms could involve “how we [women] make our proteins and how we respond to hormones.”

By identifying proteins linked to MI in women, the study helps to fill an important gap in our knowledge. “I can’t tell you how many papers don’t even look at sex differences. If we don’t look, we won’t know there are differences,” Gulati said. “In much of our cardiac research, women are underrepresented.”

The findings of this trial and others like it may lead to new approaches to prevention and treatment, Titova and Gulati agreed. Several proteins found in this study that may have a causal link with MI are already targets of drug development, they added.

Titova said other proteins may be useful in the future as biomarkers that indicate a need for preventive action.

Gulati asked, “If we can show some of the proteins are involved in the inflammatory response — if they are causal and we can prevent them upfront — can we reduce the chance of MI?” She and Titova said the many questions remaining should prove a rewarding avenue for research.

A version of this article appeared on Medscape.com.

Forty-five circulating proteins in plasma are linked to the risk for myocardial infarction (MI), showed a new study that confirms some known associations and identifies new ones. Several proteins are associated with MI in women but not men, and some proteins linked with MI in both men and women are more strongly associated with MI in women.

“We hope that our study will shed light on pathways in MI,” said principal author Olga Titova, PhD, an epidemiologist at Uppsala University in Uppsala, Sweden. The work was published in the European Heart Journal.

Martha Gulati, MD, a cardiologist and associate director of the Barbra Streisand Women’s Heart Center at Cedars-Sinai Medical Center in Los Angeles and coauthor of an accompanying editorial, said the novel discovery of different patterns between men and women makes this an exciting study. The findings “highlight that sex differences in disease phenotype begin at the molecular level,” she said.

Titova and her team analyzed thousands of patients in two databases — one in Sweden (11,751 patients), the other in the United Kingdom (51,613 patients) — to discover proteins in the patients who went on to have an MI. Using one database to discover biomarkers and a second to replicate the findings is a common approach, said Titova.

Casting a Wide Net to Catch Proteins

The two databases “make findings more generalizable, allow us to confirm robust associations, and help minimize the risk of false positives.” The two databases mean researchers are more confident that the findings can be applied across populations, Titova added.

A total of 44 proteins were associated with later MI in both databases, adjusted for common MI risk factors as well as such factors as education, diet, physical activity, and alcohol intake, Titova explained. An additional protein was included from the first database that was unavailable in the second. Some of the proteins have been found in other studies, and this study confirms the link. Others were new, and a few appear to protect patients from MI.

“Most of the proteins are related to or involved in inflammation and atherosclerosis,” said Titova.

This is the first study to cast such a wide net, Titova pointed out. While several proteins have previously been linked to MI, most earlier studies have focused on specific proteins in populations that already have coronary artery disease or have involved cohorts of men only.

But she stresses that this study poses more questions than it answers. More research is needed to determine how proteins are involved in pathways leading to MI. The study found that some proteins may be mediators of general cardiovascular disease risk, whereas others are involved in mechanisms specifically linked to MI. Many proteins are involved in atherosclerosis, thrombosis, inflammation, immune system–related pathways, injury and tissue repair, coagulation, bone homeostasis, and iron metabolism.

“At this point, some [proteins] appear to be causal, some seem to be an association,” said Titova. It remains to be determined “which are on the causal path, which are potential biomarkers, which are going to shed light on the mechanisms” of MI.

The study took a step toward determining which proteins might be involved in causing MI through an analysis of some protein levels determined by genetics. This found three proteins linked to a higher risk for MI and three linked to a lower risk.

It’s Different for Women

Thirteen of the proteins were linked with later MI in women, either exclusively or more strongly than in men. Many of these associations were replicated in the second database, showing an alignment across populations.

Titova said the reason for the sex difference remains a mystery. “We have to go to the molecular level. It could be a consequence of risk factors affecting the sexes differently or different biology” between men and women.

Gulati, who specializes in women’s heart health, explained, “We know inflammation is much more prevalent in women and is the pathway to cardiovascular disease.” She points out that noncardiac inflammatory diseases are also more prevalent in women. Other biomarkers for inflammation, such as C-reactive protein, are higher in women than in men. She thinks the underlying mechanisms could involve “how we [women] make our proteins and how we respond to hormones.”

By identifying proteins linked to MI in women, the study helps to fill an important gap in our knowledge. “I can’t tell you how many papers don’t even look at sex differences. If we don’t look, we won’t know there are differences,” Gulati said. “In much of our cardiac research, women are underrepresented.”

The findings of this trial and others like it may lead to new approaches to prevention and treatment, Titova and Gulati agreed. Several proteins found in this study that may have a causal link with MI are already targets of drug development, they added.

Titova said other proteins may be useful in the future as biomarkers that indicate a need for preventive action.

Gulati asked, “If we can show some of the proteins are involved in the inflammatory response — if they are causal and we can prevent them upfront — can we reduce the chance of MI?” She and Titova said the many questions remaining should prove a rewarding avenue for research.

A version of this article appeared on Medscape.com.

Forty-five circulating proteins in plasma are linked to the risk for myocardial infarction (MI), showed a new study that confirms some known associations and identifies new ones. Several proteins are associated with MI in women but not men, and some proteins linked with MI in both men and women are more strongly associated with MI in women.

“We hope that our study will shed light on pathways in MI,” said principal author Olga Titova, PhD, an epidemiologist at Uppsala University in Uppsala, Sweden. The work was published in the European Heart Journal.

Martha Gulati, MD, a cardiologist and associate director of the Barbra Streisand Women’s Heart Center at Cedars-Sinai Medical Center in Los Angeles and coauthor of an accompanying editorial, said the novel discovery of different patterns between men and women makes this an exciting study. The findings “highlight that sex differences in disease phenotype begin at the molecular level,” she said.

Titova and her team analyzed thousands of patients in two databases — one in Sweden (11,751 patients), the other in the United Kingdom (51,613 patients) — to discover proteins in the patients who went on to have an MI. Using one database to discover biomarkers and a second to replicate the findings is a common approach, said Titova.

Casting a Wide Net to Catch Proteins

The two databases “make findings more generalizable, allow us to confirm robust associations, and help minimize the risk of false positives.” The two databases mean researchers are more confident that the findings can be applied across populations, Titova added.

A total of 44 proteins were associated with later MI in both databases, adjusted for common MI risk factors as well as such factors as education, diet, physical activity, and alcohol intake, Titova explained. An additional protein was included from the first database that was unavailable in the second. Some of the proteins have been found in other studies, and this study confirms the link. Others were new, and a few appear to protect patients from MI.

“Most of the proteins are related to or involved in inflammation and atherosclerosis,” said Titova.

This is the first study to cast such a wide net, Titova pointed out. While several proteins have previously been linked to MI, most earlier studies have focused on specific proteins in populations that already have coronary artery disease or have involved cohorts of men only.

But she stresses that this study poses more questions than it answers. More research is needed to determine how proteins are involved in pathways leading to MI. The study found that some proteins may be mediators of general cardiovascular disease risk, whereas others are involved in mechanisms specifically linked to MI. Many proteins are involved in atherosclerosis, thrombosis, inflammation, immune system–related pathways, injury and tissue repair, coagulation, bone homeostasis, and iron metabolism.

“At this point, some [proteins] appear to be causal, some seem to be an association,” said Titova. It remains to be determined “which are on the causal path, which are potential biomarkers, which are going to shed light on the mechanisms” of MI.

The study took a step toward determining which proteins might be involved in causing MI through an analysis of some protein levels determined by genetics. This found three proteins linked to a higher risk for MI and three linked to a lower risk.

It’s Different for Women

Thirteen of the proteins were linked with later MI in women, either exclusively or more strongly than in men. Many of these associations were replicated in the second database, showing an alignment across populations.

Titova said the reason for the sex difference remains a mystery. “We have to go to the molecular level. It could be a consequence of risk factors affecting the sexes differently or different biology” between men and women.

Gulati, who specializes in women’s heart health, explained, “We know inflammation is much more prevalent in women and is the pathway to cardiovascular disease.” She points out that noncardiac inflammatory diseases are also more prevalent in women. Other biomarkers for inflammation, such as C-reactive protein, are higher in women than in men. She thinks the underlying mechanisms could involve “how we [women] make our proteins and how we respond to hormones.”

By identifying proteins linked to MI in women, the study helps to fill an important gap in our knowledge. “I can’t tell you how many papers don’t even look at sex differences. If we don’t look, we won’t know there are differences,” Gulati said. “In much of our cardiac research, women are underrepresented.”

The findings of this trial and others like it may lead to new approaches to prevention and treatment, Titova and Gulati agreed. Several proteins found in this study that may have a causal link with MI are already targets of drug development, they added.

Titova said other proteins may be useful in the future as biomarkers that indicate a need for preventive action.

Gulati asked, “If we can show some of the proteins are involved in the inflammatory response — if they are causal and we can prevent them upfront — can we reduce the chance of MI?” She and Titova said the many questions remaining should prove a rewarding avenue for research.

A version of this article appeared on Medscape.com.

More than two thirds of American counties don’t have an endocrinologist, according to a new analysis by GoodRx, a company that provides discount coupons for medications.

A total of 50 million people who live in the 2168 counties without a practicing endocrinologist are at a higher risk for poor health outcomes, according to the analysis. 

The author reported that individuals who live in endocrinology “deserts” are 12% more likely to die from endocrine-related conditions and have higher rates of diabetes, obesity, and stroke than those who live in counties where there are endocrinologists.

GoodRx’s finely detailed maps show that endocrinologists are clustered on the coasts and around major cities. Many counties have just a single endocrinologist and no pediatric endocrinologists.

Endocrinologists are not flocking to areas with a high type 2 diabetes prevalence — such as southern states, many parts of Texas, and counties with high concentrations of Native Americans or Alaskan Natives.

The maps speak volumes about disparities. In Sabine Parish, Louisiana, which shares a border with east Texas, the adult diabetes prevalence is 14%. The age-adjusted diabetes death rate is 52.6 per 100,000, in a population of 16,936 adults. There are no endocrinologists in that parish and one in a bordering parish.

In the entire state of Alaska, there are a total of two adult endocrinologists — one in Anchorage County and one in Fairbanks County — and two pediatric endocrinologists, both in Anchorage.

Buffalo County, South Dakota, which has no endocrinologists and is dominated by the Crow Creek Reservation, has a diabetes prevalence of 16.6% and a diabetes death rate of 143.3 per 100,000.

Connecticut’s Hartford County, however, has 69 adult endocrinologists and 9 pediatric endocrinologists. The adult diabetes prevalence is 0%, and the death rate is 26.3 per 100,000, in a population of 896,854.

To come up with its maps, GoodRx used population estimates from the 2024 Centers for Disease Control and Prevention (CDC) Places dataset and calculated adult diabetes rates and age-adjusted diabetes-related death rates per 100,000 using the 2024 CDC Places and CDC Wonder datasets. Data on the number of practicing endocrinologists came from HealthLink Dimensions, a company that provides databases for marketing purposes.

Robert Lash, MD, chief medical officer for The Endocrine Society, said that the GoodRx data are not especially new. Endocrinology “deserts” have existed for a decade or more, Lash said.

The GoodRx analysis concluded that a lack of endocrinologists in the “desert” counties directly led to higher death rates in those areas. “This is much more an association that it is causation,” countered Lash, noting that the deserts tend to align with healthcare professional shortage areas.

GoodRx also acknowledged the overlap and said that it could mean less access to primary care. In turn, “many patients may not even receive a diagnosis for endocrine-related conditions, let alone the specialized care they need,” wrote the analyst. “Preventable conditions like diabetes spiral into severe complications.”

Lash said seeking out a primary care doctor is one option for those without access to an endocrinologist. Telemedicine has also helped expand access, said Lash, adding that endocrinologists have been among the more frequent users.

Even so, the shortage of endocrinologists is an ongoing problem, he said. Only about 5000-6000 endocrinologists are actively practicing, estimates The Endocrine Society.

Fewer medical school graduates are choosing endocrinology, in part because of the lack of compensation, said Lash.

The society has begun a push to interest more students. Starting in 2024, The Society awarded grants to 10 medical schools to start endocrinology interest groups. The Medical School Engagement Program also sponsors two students for a VIP-type experience at the annual scientific meeting.

The hope is to boost interest in fellowships, which come after 3 years of internal medicine residency. Currently, there are only about 11 applicants for every 10 fellowship spots, said Lash.

It may be a while before the society’s experiment bears fruit. Those entering medical school in 2024 would not be eligible for fellowship until 2031, noted Lash.

“We’re in this for the long haul,” he said. “We know that this problem is not going to get solved overnight.”

A version of this article appeared on Medscape.com.

More than two thirds of American counties don’t have an endocrinologist, according to a new analysis by GoodRx, a company that provides discount coupons for medications.

A total of 50 million people who live in the 2168 counties without a practicing endocrinologist are at a higher risk for poor health outcomes, according to the analysis. 

The author reported that individuals who live in endocrinology “deserts” are 12% more likely to die from endocrine-related conditions and have higher rates of diabetes, obesity, and stroke than those who live in counties where there are endocrinologists.

GoodRx’s finely detailed maps show that endocrinologists are clustered on the coasts and around major cities. Many counties have just a single endocrinologist and no pediatric endocrinologists.

Endocrinologists are not flocking to areas with a high type 2 diabetes prevalence — such as southern states, many parts of Texas, and counties with high concentrations of Native Americans or Alaskan Natives.

The maps speak volumes about disparities. In Sabine Parish, Louisiana, which shares a border with east Texas, the adult diabetes prevalence is 14%. The age-adjusted diabetes death rate is 52.6 per 100,000, in a population of 16,936 adults. There are no endocrinologists in that parish and one in a bordering parish.

In the entire state of Alaska, there are a total of two adult endocrinologists — one in Anchorage County and one in Fairbanks County — and two pediatric endocrinologists, both in Anchorage.

Buffalo County, South Dakota, which has no endocrinologists and is dominated by the Crow Creek Reservation, has a diabetes prevalence of 16.6% and a diabetes death rate of 143.3 per 100,000.

Connecticut’s Hartford County, however, has 69 adult endocrinologists and 9 pediatric endocrinologists. The adult diabetes prevalence is 0%, and the death rate is 26.3 per 100,000, in a population of 896,854.

To come up with its maps, GoodRx used population estimates from the 2024 Centers for Disease Control and Prevention (CDC) Places dataset and calculated adult diabetes rates and age-adjusted diabetes-related death rates per 100,000 using the 2024 CDC Places and CDC Wonder datasets. Data on the number of practicing endocrinologists came from HealthLink Dimensions, a company that provides databases for marketing purposes.

Robert Lash, MD, chief medical officer for The Endocrine Society, said that the GoodRx data are not especially new. Endocrinology “deserts” have existed for a decade or more, Lash said.

The GoodRx analysis concluded that a lack of endocrinologists in the “desert” counties directly led to higher death rates in those areas. “This is much more an association that it is causation,” countered Lash, noting that the deserts tend to align with healthcare professional shortage areas.

GoodRx also acknowledged the overlap and said that it could mean less access to primary care. In turn, “many patients may not even receive a diagnosis for endocrine-related conditions, let alone the specialized care they need,” wrote the analyst. “Preventable conditions like diabetes spiral into severe complications.”

Lash said seeking out a primary care doctor is one option for those without access to an endocrinologist. Telemedicine has also helped expand access, said Lash, adding that endocrinologists have been among the more frequent users.

Even so, the shortage of endocrinologists is an ongoing problem, he said. Only about 5000-6000 endocrinologists are actively practicing, estimates The Endocrine Society.

Fewer medical school graduates are choosing endocrinology, in part because of the lack of compensation, said Lash.

The society has begun a push to interest more students. Starting in 2024, The Society awarded grants to 10 medical schools to start endocrinology interest groups. The Medical School Engagement Program also sponsors two students for a VIP-type experience at the annual scientific meeting.

The hope is to boost interest in fellowships, which come after 3 years of internal medicine residency. Currently, there are only about 11 applicants for every 10 fellowship spots, said Lash.

It may be a while before the society’s experiment bears fruit. Those entering medical school in 2024 would not be eligible for fellowship until 2031, noted Lash.

“We’re in this for the long haul,” he said. “We know that this problem is not going to get solved overnight.”

A version of this article appeared on Medscape.com.

More than two thirds of American counties don’t have an endocrinologist, according to a new analysis by GoodRx, a company that provides discount coupons for medications.

A total of 50 million people who live in the 2168 counties without a practicing endocrinologist are at a higher risk for poor health outcomes, according to the analysis. 

The author reported that individuals who live in endocrinology “deserts” are 12% more likely to die from endocrine-related conditions and have higher rates of diabetes, obesity, and stroke than those who live in counties where there are endocrinologists.

GoodRx’s finely detailed maps show that endocrinologists are clustered on the coasts and around major cities. Many counties have just a single endocrinologist and no pediatric endocrinologists.

Endocrinologists are not flocking to areas with a high type 2 diabetes prevalence — such as southern states, many parts of Texas, and counties with high concentrations of Native Americans or Alaskan Natives.

The maps speak volumes about disparities. In Sabine Parish, Louisiana, which shares a border with east Texas, the adult diabetes prevalence is 14%. The age-adjusted diabetes death rate is 52.6 per 100,000, in a population of 16,936 adults. There are no endocrinologists in that parish and one in a bordering parish.

In the entire state of Alaska, there are a total of two adult endocrinologists — one in Anchorage County and one in Fairbanks County — and two pediatric endocrinologists, both in Anchorage.

Buffalo County, South Dakota, which has no endocrinologists and is dominated by the Crow Creek Reservation, has a diabetes prevalence of 16.6% and a diabetes death rate of 143.3 per 100,000.

Connecticut’s Hartford County, however, has 69 adult endocrinologists and 9 pediatric endocrinologists. The adult diabetes prevalence is 0%, and the death rate is 26.3 per 100,000, in a population of 896,854.

To come up with its maps, GoodRx used population estimates from the 2024 Centers for Disease Control and Prevention (CDC) Places dataset and calculated adult diabetes rates and age-adjusted diabetes-related death rates per 100,000 using the 2024 CDC Places and CDC Wonder datasets. Data on the number of practicing endocrinologists came from HealthLink Dimensions, a company that provides databases for marketing purposes.

Robert Lash, MD, chief medical officer for The Endocrine Society, said that the GoodRx data are not especially new. Endocrinology “deserts” have existed for a decade or more, Lash said.

The GoodRx analysis concluded that a lack of endocrinologists in the “desert” counties directly led to higher death rates in those areas. “This is much more an association that it is causation,” countered Lash, noting that the deserts tend to align with healthcare professional shortage areas.

GoodRx also acknowledged the overlap and said that it could mean less access to primary care. In turn, “many patients may not even receive a diagnosis for endocrine-related conditions, let alone the specialized care they need,” wrote the analyst. “Preventable conditions like diabetes spiral into severe complications.”

Lash said seeking out a primary care doctor is one option for those without access to an endocrinologist. Telemedicine has also helped expand access, said Lash, adding that endocrinologists have been among the more frequent users.

Even so, the shortage of endocrinologists is an ongoing problem, he said. Only about 5000-6000 endocrinologists are actively practicing, estimates The Endocrine Society.

Fewer medical school graduates are choosing endocrinology, in part because of the lack of compensation, said Lash.

The society has begun a push to interest more students. Starting in 2024, The Society awarded grants to 10 medical schools to start endocrinology interest groups. The Medical School Engagement Program also sponsors two students for a VIP-type experience at the annual scientific meeting.

The hope is to boost interest in fellowships, which come after 3 years of internal medicine residency. Currently, there are only about 11 applicants for every 10 fellowship spots, said Lash.

It may be a while before the society’s experiment bears fruit. Those entering medical school in 2024 would not be eligible for fellowship until 2031, noted Lash.

“We’re in this for the long haul,” he said. “We know that this problem is not going to get solved overnight.”

A version of this article appeared on Medscape.com.

TOPLINE:

COVID-19 survivors show a more pronounced decline in kidney function than those who recover from pneumonia caused by other infections. This decline in kidney function, measured by the estimated glomerular filtration rate (eGFR), is particularly steep among individuals who require hospitalization for COVID-19.

METHODOLOGY:

• SARS-CoV-2, the virus that causes COVID-19, has been associated with acute kidney injury, but its potential impact on long-term kidney function remains unclear.
• Researchers investigated the decline in kidney function after COVID-19 vs pneumonia by including all hospitalized and nonhospitalized adults from the Stockholm Creatinine Measurements Project who had at least one eGFR measurement in the 2 years before a positive COVID-19 test result or pneumonia diagnosis.
• Overall, 134,565 individuals (median age, 51 years; 55.6% women) who had their first SARS-CoV-2 infection between February 2020 and January 2022 were included, of whom 13.3% required hospitalization within 28 days of their first positive COVID-19 test result.
• They were compared with 35,987 patients (median age, 71 years; 53.8% women) who were diagnosed with pneumonia between February 2018 and January 2020; 46.5% of them required hospitalization.
• The primary outcome measure focused on the mean annual change in eGFR slopes before and after each infection; the secondary outcome assessed was the annual change in postinfection eGFR slopes between COVID-19 and pneumonia cases.

TAKEAWAY:

• Before COVID-19, eGFR changes were minimal, but after the infection, the average decline increased to 4.1 (95% CI, 3.8-4.4) mL/min/1.73 m²; however, in the pneumonia cohort, a decline in eGFR was noted both before and after the infection.
• After COVID-19, the mean annual decline in eGFR was 3.4% (95% CI, 3.2%-3.5%), increasing to 5.4% (95% CI, 5.2%-5.6%) for those who were hospitalized.
• In contrast, the pneumonia group experienced an average annual decline of 2.3% (95% CI, 2.1%-2.5%) after the infection, which remained unchanged when analyzing only patients who were hospitalized.
• The risk for a 25% reduction in eGFR was higher in patients with COVID-19 than in those with pneumonia (hazard ratio [HR], 1.19; 95% CI, 1.07-1.34), with the risk being even higher among those who required hospitalization (HR, 1.42; 95% CI, 1.22-1.64).

IN PRACTICE:

“These findings help inform decisions regarding the need to monitor kidney function in survivors of COVID-19 and could have implications for policymakers regarding future healthcare planning and kidney service provision,” the authors wrote.

SOURCE:

This study was led by Viyaasan Mahalingasivam, MPhil, London School of Hygiene & Tropical Medicine, London, England. It was published online in JAMA Network Open.

LIMITATIONS:

This study lacked information on important confounders such as ethnicity and body mass index. The follow-up period was not long enough to fully evaluate the long-term association of COVID-19 with kidney function. Some individuals may have been misclassified as nonhospitalized if their first infection was mild and a subsequent infection required hospitalization.

DISCLOSURES:

This study was supported by grants from the National Institute for Health and Care Research, Njurfonden, Stig and Gunborg Westman Foundation, and the Swedish Research Council. One author reported receiving a Career Development Award from the National Institute for Health and Care Research, and another author reported receiving grants from Njurfonden, Stig and Gunborg Westman Foundation, Swedish Research Council, Swedish Heart Lung Foundation, and Region Stockholm during the conduct of the study.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

COVID-19 survivors show a more pronounced decline in kidney function than those who recover from pneumonia caused by other infections. This decline in kidney function, measured by the estimated glomerular filtration rate (eGFR), is particularly steep among individuals who require hospitalization for COVID-19.

METHODOLOGY:

• SARS-CoV-2, the virus that causes COVID-19, has been associated with acute kidney injury, but its potential impact on long-term kidney function remains unclear.
• Researchers investigated the decline in kidney function after COVID-19 vs pneumonia by including all hospitalized and nonhospitalized adults from the Stockholm Creatinine Measurements Project who had at least one eGFR measurement in the 2 years before a positive COVID-19 test result or pneumonia diagnosis.
• Overall, 134,565 individuals (median age, 51 years; 55.6% women) who had their first SARS-CoV-2 infection between February 2020 and January 2022 were included, of whom 13.3% required hospitalization within 28 days of their first positive COVID-19 test result.
• They were compared with 35,987 patients (median age, 71 years; 53.8% women) who were diagnosed with pneumonia between February 2018 and January 2020; 46.5% of them required hospitalization.
• The primary outcome measure focused on the mean annual change in eGFR slopes before and after each infection; the secondary outcome assessed was the annual change in postinfection eGFR slopes between COVID-19 and pneumonia cases.

TAKEAWAY:

• Before COVID-19, eGFR changes were minimal, but after the infection, the average decline increased to 4.1 (95% CI, 3.8-4.4) mL/min/1.73 m²; however, in the pneumonia cohort, a decline in eGFR was noted both before and after the infection.
• After COVID-19, the mean annual decline in eGFR was 3.4% (95% CI, 3.2%-3.5%), increasing to 5.4% (95% CI, 5.2%-5.6%) for those who were hospitalized.
• In contrast, the pneumonia group experienced an average annual decline of 2.3% (95% CI, 2.1%-2.5%) after the infection, which remained unchanged when analyzing only patients who were hospitalized.
• The risk for a 25% reduction in eGFR was higher in patients with COVID-19 than in those with pneumonia (hazard ratio [HR], 1.19; 95% CI, 1.07-1.34), with the risk being even higher among those who required hospitalization (HR, 1.42; 95% CI, 1.22-1.64).

IN PRACTICE:

“These findings help inform decisions regarding the need to monitor kidney function in survivors of COVID-19 and could have implications for policymakers regarding future healthcare planning and kidney service provision,” the authors wrote.

SOURCE:

This study was led by Viyaasan Mahalingasivam, MPhil, London School of Hygiene & Tropical Medicine, London, England. It was published online in JAMA Network Open.

LIMITATIONS:

This study lacked information on important confounders such as ethnicity and body mass index. The follow-up period was not long enough to fully evaluate the long-term association of COVID-19 with kidney function. Some individuals may have been misclassified as nonhospitalized if their first infection was mild and a subsequent infection required hospitalization.

DISCLOSURES:

This study was supported by grants from the National Institute for Health and Care Research, Njurfonden, Stig and Gunborg Westman Foundation, and the Swedish Research Council. One author reported receiving a Career Development Award from the National Institute for Health and Care Research, and another author reported receiving grants from Njurfonden, Stig and Gunborg Westman Foundation, Swedish Research Council, Swedish Heart Lung Foundation, and Region Stockholm during the conduct of the study.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

COVID-19 survivors show a more pronounced decline in kidney function than those who recover from pneumonia caused by other infections. This decline in kidney function, measured by the estimated glomerular filtration rate (eGFR), is particularly steep among individuals who require hospitalization for COVID-19.

METHODOLOGY:

• SARS-CoV-2, the virus that causes COVID-19, has been associated with acute kidney injury, but its potential impact on long-term kidney function remains unclear.
• Researchers investigated the decline in kidney function after COVID-19 vs pneumonia by including all hospitalized and nonhospitalized adults from the Stockholm Creatinine Measurements Project who had at least one eGFR measurement in the 2 years before a positive COVID-19 test result or pneumonia diagnosis.
• Overall, 134,565 individuals (median age, 51 years; 55.6% women) who had their first SARS-CoV-2 infection between February 2020 and January 2022 were included, of whom 13.3% required hospitalization within 28 days of their first positive COVID-19 test result.
• They were compared with 35,987 patients (median age, 71 years; 53.8% women) who were diagnosed with pneumonia between February 2018 and January 2020; 46.5% of them required hospitalization.
• The primary outcome measure focused on the mean annual change in eGFR slopes before and after each infection; the secondary outcome assessed was the annual change in postinfection eGFR slopes between COVID-19 and pneumonia cases.

TAKEAWAY:

• Before COVID-19, eGFR changes were minimal, but after the infection, the average decline increased to 4.1 (95% CI, 3.8-4.4) mL/min/1.73 m²; however, in the pneumonia cohort, a decline in eGFR was noted both before and after the infection.
• After COVID-19, the mean annual decline in eGFR was 3.4% (95% CI, 3.2%-3.5%), increasing to 5.4% (95% CI, 5.2%-5.6%) for those who were hospitalized.
• In contrast, the pneumonia group experienced an average annual decline of 2.3% (95% CI, 2.1%-2.5%) after the infection, which remained unchanged when analyzing only patients who were hospitalized.
• The risk for a 25% reduction in eGFR was higher in patients with COVID-19 than in those with pneumonia (hazard ratio [HR], 1.19; 95% CI, 1.07-1.34), with the risk being even higher among those who required hospitalization (HR, 1.42; 95% CI, 1.22-1.64).

IN PRACTICE:

“These findings help inform decisions regarding the need to monitor kidney function in survivors of COVID-19 and could have implications for policymakers regarding future healthcare planning and kidney service provision,” the authors wrote.

SOURCE:

This study was led by Viyaasan Mahalingasivam, MPhil, London School of Hygiene & Tropical Medicine, London, England. It was published online in JAMA Network Open.

LIMITATIONS:

This study lacked information on important confounders such as ethnicity and body mass index. The follow-up period was not long enough to fully evaluate the long-term association of COVID-19 with kidney function. Some individuals may have been misclassified as nonhospitalized if their first infection was mild and a subsequent infection required hospitalization.

DISCLOSURES:

This study was supported by grants from the National Institute for Health and Care Research, Njurfonden, Stig and Gunborg Westman Foundation, and the Swedish Research Council. One author reported receiving a Career Development Award from the National Institute for Health and Care Research, and another author reported receiving grants from Njurfonden, Stig and Gunborg Westman Foundation, Swedish Research Council, Swedish Heart Lung Foundation, and Region Stockholm during the conduct of the study.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

John Bolecek, 41, of Richmond, Virginia, was diagnosed with long COVID in May of 2022. While his acute infection was mild, once everyone else in his family had recovered, the heavy fatigue he experienced from the start has never lifted.

“When I wake up in the morning, I feel like I haven’t gone to sleep at all,” Bolecek said. “It’s this super fatigue that’s just never gone away.”

The urban planner who once rode his bike to work daily and spent weekends cycling had to quit working and now can barely get through a light walk before long COVID symptoms of post-exertional malaise, an intense fatigue after previously tolerated physical or mental activity, set in. His unrefreshing sleep, fatigue, and dysautonomia — a disruption of the autonomic nervous system that causes dizziness, heart rate changes, and nausea — have made it nearly impossible to share household duties with his wife. She has to do most of the cooking, cleaning, and tending to their two sons, ages 6 and 8 years.

It’s an increasingly familiar story for those hit with long COVID in their prime, a period of life when young and middle-aged adults are the most productive and the busiest, often in the thick of parenting while also taking care of their aging parents. And it’s a group that is among the hardest hit by long COVID both because of the sheer number of patients with the condition and the mental and financial strain that it’s putting on this age group. According to the Centers for Disease Control and Prevention (CDC), 6.9% of adults aged 18-34 years and 8.9% of adults aged 35-49 years have the disorder compared with 4.1% of older adults aged > 65 years who are the least likely to have long COVID.

In a study published recently in Scientific Reports, researchers found that in a population of California residents with long COVID, older individuals (who were sicker to start) had more severe symptoms associated with the condition. But researchers also found that younger people (aged 18-49 years) were more likely to experience symptoms that reduced their productivity and quality of life. They suggested this is both because they have more to do in a given day and because they have a longer life ahead of them living with a chronic condition.

“Much of California’s population falls within the 18-49 age group, [so] we would expect to see the highest overall burden coming from these individuals,” said lead study author Sophie Zhu, a researcher in the Division of Communicable Disease Control at the California Department of Public Health.

 

The Impact on Work and Life Productivity

Adults and especially those in middle age tend to have a lot of competing stressors during this period of life, said Nisha Viswanathan, MD, director of the UCLA Health Long COVID program. “Patients may need to decrease some of the pressures of life for their health and that can be impossible to do because they have so many other people who are depending on them.”

It’s a different set of circumstances compared with older individuals who may have more severe symptoms because they have underlying conditions. But older Americans are also more likely to be retired and don’t have children who are financially dependent on them. Previous research has shown the burden that long COVID is having on the workforce. A study published in the August 2023 edition of The Lancet Regional Health found that 5.8% of participating patients with long COVID reported occupational changes like moving to part time or remote work, including 1.6% who had completely dropped out of the workforce.

Middle age is also a time of life when patients may not have time to seek the care they need. The chronic nature of long COVID means that treatment can be time consuming and expensive, all of which drains resources from patients who are often supporting spouses, children, and sometimes older parents. A study published in Disability and Health Journal found that patients with long COVID have significantly higher rates of housing instability and financial concerns, such as worries about paying rent or a mortgage, than those without the condition.

 

The Financial Strain of Long COVID

For those who can’t work, the process of applying for long-term disability can also be complicated. That’s especially true for people whose illness keeps them from doing even basic tasks like filling out paperwork and dealing with disability insurance claims. It requires those applying as a result of their long COVID symptoms to show all records connected to long COVID as well as a medical history, the beginning of their symptoms, and their current treatments.

Even then, many patients complain of having their claims rejected, which can be financially disastrous to families already struggling to get by. Still, experts contend that it’s important to understand that as of July 2021, long COVID is considered a disability under the Americans with Disabilities Act (ADA).

“Long COVID is recognized as a disability under Section 504 of the ADA, and yet day after day, we see violations of the ADA for people with long COVID not getting the accommodations that they need in order to work,” said David Putrino, PhD, the Nash Family director of the Cohen Center for Recovery from Complex Chronic Illness at Mount Sinai in New York City and a renowned expert in long COVID.

He added that short- and long-term disability claims are sometimes denied because of a lack of diagnostic testing to prove a patient has the condition. “This is nonsensical and absurd because the CDC does not require a blood test for the diagnosis of long COVID. It’s at your physician’s discretion,” Putrino said.

Viswanathan agreed. She said that for many of her patients, getting long-term disability has been particularly challenging because there’s no blood test for long COVID to prove patients have the condition. “As a result, for many of our patients, especially when they’re young, they may have to return to work in one form or another,” Viswanathan said.

 

The Impact of Long COVID on Quality of Life

What’s worse, the full impact is yet unknown because this is likely an underestimated cohort as many of these patients had mild cases of acute COVID-19 and fewer underlying conditions. For others, their long COVID is undiagnosed.

“Much of the impact on productivity and quality of life for this group remains hidden,” said Ziyad Al-Aly, MD, a global expert on long COVID and chief of research and development at the Veterans Affairs St. Louis Health Care System in Missouri.

Unfortunately, the impact on Bolecek’s life isn’t so hidden. He can’t work, which has been a financial stressor on the family. He spends much of the day in bed so that he can help with a few things when his wife gets home from work. He can’t cycle anymore and, as a result, has lost many of the friends associated with his favorite hobby.

But he remains hopeful, and more than anything else, he’s thankful for his family. His wife and kids have given him the strength to push on even when the days are hard. “I just don’t know where I’d be without them,” Bolecek said.

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

John Bolecek, 41, of Richmond, Virginia, was diagnosed with long COVID in May of 2022. While his acute infection was mild, once everyone else in his family had recovered, the heavy fatigue he experienced from the start has never lifted.

“When I wake up in the morning, I feel like I haven’t gone to sleep at all,” Bolecek said. “It’s this super fatigue that’s just never gone away.”

The urban planner who once rode his bike to work daily and spent weekends cycling had to quit working and now can barely get through a light walk before long COVID symptoms of post-exertional malaise, an intense fatigue after previously tolerated physical or mental activity, set in. His unrefreshing sleep, fatigue, and dysautonomia — a disruption of the autonomic nervous system that causes dizziness, heart rate changes, and nausea — have made it nearly impossible to share household duties with his wife. She has to do most of the cooking, cleaning, and tending to their two sons, ages 6 and 8 years.

It’s an increasingly familiar story for those hit with long COVID in their prime, a period of life when young and middle-aged adults are the most productive and the busiest, often in the thick of parenting while also taking care of their aging parents. And it’s a group that is among the hardest hit by long COVID both because of the sheer number of patients with the condition and the mental and financial strain that it’s putting on this age group. According to the Centers for Disease Control and Prevention (CDC), 6.9% of adults aged 18-34 years and 8.9% of adults aged 35-49 years have the disorder compared with 4.1% of older adults aged > 65 years who are the least likely to have long COVID.

In a study published recently in Scientific Reports, researchers found that in a population of California residents with long COVID, older individuals (who were sicker to start) had more severe symptoms associated with the condition. But researchers also found that younger people (aged 18-49 years) were more likely to experience symptoms that reduced their productivity and quality of life. They suggested this is both because they have more to do in a given day and because they have a longer life ahead of them living with a chronic condition.

“Much of California’s population falls within the 18-49 age group, [so] we would expect to see the highest overall burden coming from these individuals,” said lead study author Sophie Zhu, a researcher in the Division of Communicable Disease Control at the California Department of Public Health.

 

The Impact on Work and Life Productivity

Adults and especially those in middle age tend to have a lot of competing stressors during this period of life, said Nisha Viswanathan, MD, director of the UCLA Health Long COVID program. “Patients may need to decrease some of the pressures of life for their health and that can be impossible to do because they have so many other people who are depending on them.”

It’s a different set of circumstances compared with older individuals who may have more severe symptoms because they have underlying conditions. But older Americans are also more likely to be retired and don’t have children who are financially dependent on them. Previous research has shown the burden that long COVID is having on the workforce. A study published in the August 2023 edition of The Lancet Regional Health found that 5.8% of participating patients with long COVID reported occupational changes like moving to part time or remote work, including 1.6% who had completely dropped out of the workforce.

Middle age is also a time of life when patients may not have time to seek the care they need. The chronic nature of long COVID means that treatment can be time consuming and expensive, all of which drains resources from patients who are often supporting spouses, children, and sometimes older parents. A study published in Disability and Health Journal found that patients with long COVID have significantly higher rates of housing instability and financial concerns, such as worries about paying rent or a mortgage, than those without the condition.

 

The Financial Strain of Long COVID

For those who can’t work, the process of applying for long-term disability can also be complicated. That’s especially true for people whose illness keeps them from doing even basic tasks like filling out paperwork and dealing with disability insurance claims. It requires those applying as a result of their long COVID symptoms to show all records connected to long COVID as well as a medical history, the beginning of their symptoms, and their current treatments.

Even then, many patients complain of having their claims rejected, which can be financially disastrous to families already struggling to get by. Still, experts contend that it’s important to understand that as of July 2021, long COVID is considered a disability under the Americans with Disabilities Act (ADA).

“Long COVID is recognized as a disability under Section 504 of the ADA, and yet day after day, we see violations of the ADA for people with long COVID not getting the accommodations that they need in order to work,” said David Putrino, PhD, the Nash Family director of the Cohen Center for Recovery from Complex Chronic Illness at Mount Sinai in New York City and a renowned expert in long COVID.

He added that short- and long-term disability claims are sometimes denied because of a lack of diagnostic testing to prove a patient has the condition. “This is nonsensical and absurd because the CDC does not require a blood test for the diagnosis of long COVID. It’s at your physician’s discretion,” Putrino said.

Viswanathan agreed. She said that for many of her patients, getting long-term disability has been particularly challenging because there’s no blood test for long COVID to prove patients have the condition. “As a result, for many of our patients, especially when they’re young, they may have to return to work in one form or another,” Viswanathan said.

 

The Impact of Long COVID on Quality of Life

What’s worse, the full impact is yet unknown because this is likely an underestimated cohort as many of these patients had mild cases of acute COVID-19 and fewer underlying conditions. For others, their long COVID is undiagnosed.

“Much of the impact on productivity and quality of life for this group remains hidden,” said Ziyad Al-Aly, MD, a global expert on long COVID and chief of research and development at the Veterans Affairs St. Louis Health Care System in Missouri.

Unfortunately, the impact on Bolecek’s life isn’t so hidden. He can’t work, which has been a financial stressor on the family. He spends much of the day in bed so that he can help with a few things when his wife gets home from work. He can’t cycle anymore and, as a result, has lost many of the friends associated with his favorite hobby.

But he remains hopeful, and more than anything else, he’s thankful for his family. His wife and kids have given him the strength to push on even when the days are hard. “I just don’t know where I’d be without them,” Bolecek said.

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

John Bolecek, 41, of Richmond, Virginia, was diagnosed with long COVID in May of 2022. While his acute infection was mild, once everyone else in his family had recovered, the heavy fatigue he experienced from the start has never lifted.

“When I wake up in the morning, I feel like I haven’t gone to sleep at all,” Bolecek said. “It’s this super fatigue that’s just never gone away.”

The urban planner who once rode his bike to work daily and spent weekends cycling had to quit working and now can barely get through a light walk before long COVID symptoms of post-exertional malaise, an intense fatigue after previously tolerated physical or mental activity, set in. His unrefreshing sleep, fatigue, and dysautonomia — a disruption of the autonomic nervous system that causes dizziness, heart rate changes, and nausea — have made it nearly impossible to share household duties with his wife. She has to do most of the cooking, cleaning, and tending to their two sons, ages 6 and 8 years.

It’s an increasingly familiar story for those hit with long COVID in their prime, a period of life when young and middle-aged adults are the most productive and the busiest, often in the thick of parenting while also taking care of their aging parents. And it’s a group that is among the hardest hit by long COVID both because of the sheer number of patients with the condition and the mental and financial strain that it’s putting on this age group. According to the Centers for Disease Control and Prevention (CDC), 6.9% of adults aged 18-34 years and 8.9% of adults aged 35-49 years have the disorder compared with 4.1% of older adults aged > 65 years who are the least likely to have long COVID.

In a study published recently in Scientific Reports, researchers found that in a population of California residents with long COVID, older individuals (who were sicker to start) had more severe symptoms associated with the condition. But researchers also found that younger people (aged 18-49 years) were more likely to experience symptoms that reduced their productivity and quality of life. They suggested this is both because they have more to do in a given day and because they have a longer life ahead of them living with a chronic condition.

“Much of California’s population falls within the 18-49 age group, [so] we would expect to see the highest overall burden coming from these individuals,” said lead study author Sophie Zhu, a researcher in the Division of Communicable Disease Control at the California Department of Public Health.

 

The Impact on Work and Life Productivity

Adults and especially those in middle age tend to have a lot of competing stressors during this period of life, said Nisha Viswanathan, MD, director of the UCLA Health Long COVID program. “Patients may need to decrease some of the pressures of life for their health and that can be impossible to do because they have so many other people who are depending on them.”

It’s a different set of circumstances compared with older individuals who may have more severe symptoms because they have underlying conditions. But older Americans are also more likely to be retired and don’t have children who are financially dependent on them. Previous research has shown the burden that long COVID is having on the workforce. A study published in the August 2023 edition of The Lancet Regional Health found that 5.8% of participating patients with long COVID reported occupational changes like moving to part time or remote work, including 1.6% who had completely dropped out of the workforce.

Middle age is also a time of life when patients may not have time to seek the care they need. The chronic nature of long COVID means that treatment can be time consuming and expensive, all of which drains resources from patients who are often supporting spouses, children, and sometimes older parents. A study published in Disability and Health Journal found that patients with long COVID have significantly higher rates of housing instability and financial concerns, such as worries about paying rent or a mortgage, than those without the condition.

 

The Financial Strain of Long COVID

For those who can’t work, the process of applying for long-term disability can also be complicated. That’s especially true for people whose illness keeps them from doing even basic tasks like filling out paperwork and dealing with disability insurance claims. It requires those applying as a result of their long COVID symptoms to show all records connected to long COVID as well as a medical history, the beginning of their symptoms, and their current treatments.

Even then, many patients complain of having their claims rejected, which can be financially disastrous to families already struggling to get by. Still, experts contend that it’s important to understand that as of July 2021, long COVID is considered a disability under the Americans with Disabilities Act (ADA).

“Long COVID is recognized as a disability under Section 504 of the ADA, and yet day after day, we see violations of the ADA for people with long COVID not getting the accommodations that they need in order to work,” said David Putrino, PhD, the Nash Family director of the Cohen Center for Recovery from Complex Chronic Illness at Mount Sinai in New York City and a renowned expert in long COVID.

He added that short- and long-term disability claims are sometimes denied because of a lack of diagnostic testing to prove a patient has the condition. “This is nonsensical and absurd because the CDC does not require a blood test for the diagnosis of long COVID. It’s at your physician’s discretion,” Putrino said.

Viswanathan agreed. She said that for many of her patients, getting long-term disability has been particularly challenging because there’s no blood test for long COVID to prove patients have the condition. “As a result, for many of our patients, especially when they’re young, they may have to return to work in one form or another,” Viswanathan said.

 

The Impact of Long COVID on Quality of Life

What’s worse, the full impact is yet unknown because this is likely an underestimated cohort as many of these patients had mild cases of acute COVID-19 and fewer underlying conditions. For others, their long COVID is undiagnosed.

“Much of the impact on productivity and quality of life for this group remains hidden,” said Ziyad Al-Aly, MD, a global expert on long COVID and chief of research and development at the Veterans Affairs St. Louis Health Care System in Missouri.

Unfortunately, the impact on Bolecek’s life isn’t so hidden. He can’t work, which has been a financial stressor on the family. He spends much of the day in bed so that he can help with a few things when his wife gets home from work. He can’t cycle anymore and, as a result, has lost many of the friends associated with his favorite hobby.

But he remains hopeful, and more than anything else, he’s thankful for his family. His wife and kids have given him the strength to push on even when the days are hard. “I just don’t know where I’d be without them,” Bolecek said.

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

TOPLINE:

Doxycycline discharge kits significantly improve guideline-directed treatment and reduce time to definitive treatment in patients with chlamydia who were discharged from the emergency department (ED). 

METHODOLOGY:

• A single-center retrospective chart review included adults with positive chlamydia tests in the ED between 2021 and 2023.
• In total, 98 received doxycycline discharge kits; 72 patients were enrolled before the implementation of discharge kits for comparison.
• There were no differences in symptoms of infection between patients who received and those who did not receive the kit.
• Main outcome was the number of patients who received treatment.
• Secondary outcomes included 90-day return visits for complaints of sexually transmitted infections and time to treatment initiation.

TAKEAWAY:

• Appropriate treatment rates rose significantly post-implementation of the discharge kit (69.1% vs 45.8%; odds ratio, 2.63; P = .002).
• Implementation of the discharge kit also reduced the time to definitive treatment from 22.7 hours to 1.3 hours (P < .001).
• No significant differences in 90-day ED return visits, time to initial treatment in the ED, and doxycycline prescription via culture callback programs between the two groups.

IN PRACTICE:

“Pharmacy-driven doxycycline discharge kits significantly increased guideline-directed treatment and decreased time to treatment for chlamydia infections in the ED population at an urban academic medical center,” the authors wrote. “Overall, this initiative overcame barriers to treatment for a significant public health issue, supporting the need for expansion to other emergency departments across the country.”

SOURCE:

The study was led by Carly Loudermilk, Department of Pharmacy, Louisville, Kentucky, and was published online on November 14, 2024, in The American Journal of Emergency Medicine.

LIMITATIONS:

Retrospective design is the main limitation and lack of insurance fill history in some patients.

DISCLOSURES:

The study received no external funding. The authors disclosed no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Doxycycline discharge kits significantly improve guideline-directed treatment and reduce time to definitive treatment in patients with chlamydia who were discharged from the emergency department (ED). 

METHODOLOGY:

• A single-center retrospective chart review included adults with positive chlamydia tests in the ED between 2021 and 2023.
• In total, 98 received doxycycline discharge kits; 72 patients were enrolled before the implementation of discharge kits for comparison.
• There were no differences in symptoms of infection between patients who received and those who did not receive the kit.
• Main outcome was the number of patients who received treatment.
• Secondary outcomes included 90-day return visits for complaints of sexually transmitted infections and time to treatment initiation.

TAKEAWAY:

• Appropriate treatment rates rose significantly post-implementation of the discharge kit (69.1% vs 45.8%; odds ratio, 2.63; P = .002).
• Implementation of the discharge kit also reduced the time to definitive treatment from 22.7 hours to 1.3 hours (P < .001).
• No significant differences in 90-day ED return visits, time to initial treatment in the ED, and doxycycline prescription via culture callback programs between the two groups.

IN PRACTICE:

“Pharmacy-driven doxycycline discharge kits significantly increased guideline-directed treatment and decreased time to treatment for chlamydia infections in the ED population at an urban academic medical center,” the authors wrote. “Overall, this initiative overcame barriers to treatment for a significant public health issue, supporting the need for expansion to other emergency departments across the country.”

SOURCE:

The study was led by Carly Loudermilk, Department of Pharmacy, Louisville, Kentucky, and was published online on November 14, 2024, in The American Journal of Emergency Medicine.

LIMITATIONS:

Retrospective design is the main limitation and lack of insurance fill history in some patients.

DISCLOSURES:

The study received no external funding. The authors disclosed no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Doxycycline discharge kits significantly improve guideline-directed treatment and reduce time to definitive treatment in patients with chlamydia who were discharged from the emergency department (ED). 

METHODOLOGY:

• A single-center retrospective chart review included adults with positive chlamydia tests in the ED between 2021 and 2023.
• In total, 98 received doxycycline discharge kits; 72 patients were enrolled before the implementation of discharge kits for comparison.
• There were no differences in symptoms of infection between patients who received and those who did not receive the kit.
• Main outcome was the number of patients who received treatment.
• Secondary outcomes included 90-day return visits for complaints of sexually transmitted infections and time to treatment initiation.

TAKEAWAY:

• Appropriate treatment rates rose significantly post-implementation of the discharge kit (69.1% vs 45.8%; odds ratio, 2.63; P = .002).
• Implementation of the discharge kit also reduced the time to definitive treatment from 22.7 hours to 1.3 hours (P < .001).
• No significant differences in 90-day ED return visits, time to initial treatment in the ED, and doxycycline prescription via culture callback programs between the two groups.

IN PRACTICE:

“Pharmacy-driven doxycycline discharge kits significantly increased guideline-directed treatment and decreased time to treatment for chlamydia infections in the ED population at an urban academic medical center,” the authors wrote. “Overall, this initiative overcame barriers to treatment for a significant public health issue, supporting the need for expansion to other emergency departments across the country.”

SOURCE:

The study was led by Carly Loudermilk, Department of Pharmacy, Louisville, Kentucky, and was published online on November 14, 2024, in The American Journal of Emergency Medicine.

LIMITATIONS:

Retrospective design is the main limitation and lack of insurance fill history in some patients.

DISCLOSURES:

The study received no external funding. The authors disclosed no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Coffee consumption is associated with the abundance of the gut bacterium Lawsonibacter asaccharolyticus, suggesting that specific foods can affect the intestinal microbiome.

METHODOLOGY:

• The researchers selected coffee as a model to investigate the interplay between specific foods and the intestinal microbial community.
• They conducted a multicohort, multiomic analysis of US and UK populations with detailed dietary information from 22,867 participants, which they then integrated with public data from 211 cohorts comprising 54,198 participants.
• They conducted various in vitro experiments to expand and validate their findings, including adding coffee to media containing the L asaccharolyticus species that had been isolated from human feces.

TAKEAWAY:

• L asaccharolyticus is highly prevalent, with about fourfold higher average abundance in coffee drinkers, and its growth is stimulated in vitro by coffee supplementation.
• The link between coffee consumption and the microbiome was highly reproducible across different populations (area under the curve, 0.89), driven largely by the presence and abundance of L asaccharolyticus.
• Similar associations were found in analyses of data from 25 countries. The prevalence of the bacterium was high in European countries with high per capita coffee consumption, such as Luxembourg, Denmark, and Sweden, and very low in countries with low per capita coffee consumption, such as China, Argentina, and India.
• Plasma metabolomics on 438 samples identified several metabolites enriched among coffee drinkers, with quinic acid and its potential derivatives associated with both coffee and L asaccharolyticus.

IN PRACTICE:

“Our study provides insights into how the gut microbiome potentially mediates the chemistry — and thus health benefits — of coffee,” the study authors wrote. “The microbial mechanisms underlying the metabolism of coffee are a step towards mapping the role of specific foods on the gut microbiome, and similar patterns of microorganism–food interactions for other dietary elements should be sought with systematic epidemiologic and metagenomic investigations.”

SOURCE:

Paolo Manghi, PhD, University of Trento, Italy, led the study, which was published online in Nature Microbiology.

LIMITATIONS:

The authors relied on food questionnaires to assess coffee intake. The study is observational, and the clinical implications are unknown.

DISCLOSURES:

This work was supported by ZOE, a biotech company, and TwinsUK, an adult twin registry funded by the Wellcome Trust, Medical Research Council, Versus Arthritis, European Union Horizon 2020, Chronic Disease Research Foundation, the National Institute for Health and Care Research — Clinical Research Network and Biomedical Research Centre based at Guy’s and St. Thomas’ NHS Foundation Trust in partnership with King’s College London. Manghi had no competing interests. Several other coauthors reported financial relationships with ZOE, and three are cofounders of the company.

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

TOPLINE:

Coffee consumption is associated with the abundance of the gut bacterium Lawsonibacter asaccharolyticus, suggesting that specific foods can affect the intestinal microbiome.

METHODOLOGY:

• The researchers selected coffee as a model to investigate the interplay between specific foods and the intestinal microbial community.
• They conducted a multicohort, multiomic analysis of US and UK populations with detailed dietary information from 22,867 participants, which they then integrated with public data from 211 cohorts comprising 54,198 participants.
• They conducted various in vitro experiments to expand and validate their findings, including adding coffee to media containing the L asaccharolyticus species that had been isolated from human feces.

TAKEAWAY:

• L asaccharolyticus is highly prevalent, with about fourfold higher average abundance in coffee drinkers, and its growth is stimulated in vitro by coffee supplementation.
• The link between coffee consumption and the microbiome was highly reproducible across different populations (area under the curve, 0.89), driven largely by the presence and abundance of L asaccharolyticus.
• Similar associations were found in analyses of data from 25 countries. The prevalence of the bacterium was high in European countries with high per capita coffee consumption, such as Luxembourg, Denmark, and Sweden, and very low in countries with low per capita coffee consumption, such as China, Argentina, and India.
• Plasma metabolomics on 438 samples identified several metabolites enriched among coffee drinkers, with quinic acid and its potential derivatives associated with both coffee and L asaccharolyticus.

IN PRACTICE:

“Our study provides insights into how the gut microbiome potentially mediates the chemistry — and thus health benefits — of coffee,” the study authors wrote. “The microbial mechanisms underlying the metabolism of coffee are a step towards mapping the role of specific foods on the gut microbiome, and similar patterns of microorganism–food interactions for other dietary elements should be sought with systematic epidemiologic and metagenomic investigations.”

SOURCE:

Paolo Manghi, PhD, University of Trento, Italy, led the study, which was published online in Nature Microbiology.

LIMITATIONS:

The authors relied on food questionnaires to assess coffee intake. The study is observational, and the clinical implications are unknown.

DISCLOSURES:

This work was supported by ZOE, a biotech company, and TwinsUK, an adult twin registry funded by the Wellcome Trust, Medical Research Council, Versus Arthritis, European Union Horizon 2020, Chronic Disease Research Foundation, the National Institute for Health and Care Research — Clinical Research Network and Biomedical Research Centre based at Guy’s and St. Thomas’ NHS Foundation Trust in partnership with King’s College London. Manghi had no competing interests. Several other coauthors reported financial relationships with ZOE, and three are cofounders of the company.

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

TOPLINE:

Coffee consumption is associated with the abundance of the gut bacterium Lawsonibacter asaccharolyticus, suggesting that specific foods can affect the intestinal microbiome.

METHODOLOGY:

• The researchers selected coffee as a model to investigate the interplay between specific foods and the intestinal microbial community.
• They conducted a multicohort, multiomic analysis of US and UK populations with detailed dietary information from 22,867 participants, which they then integrated with public data from 211 cohorts comprising 54,198 participants.
• They conducted various in vitro experiments to expand and validate their findings, including adding coffee to media containing the L asaccharolyticus species that had been isolated from human feces.

TAKEAWAY:

• L asaccharolyticus is highly prevalent, with about fourfold higher average abundance in coffee drinkers, and its growth is stimulated in vitro by coffee supplementation.
• The link between coffee consumption and the microbiome was highly reproducible across different populations (area under the curve, 0.89), driven largely by the presence and abundance of L asaccharolyticus.
• Similar associations were found in analyses of data from 25 countries. The prevalence of the bacterium was high in European countries with high per capita coffee consumption, such as Luxembourg, Denmark, and Sweden, and very low in countries with low per capita coffee consumption, such as China, Argentina, and India.
• Plasma metabolomics on 438 samples identified several metabolites enriched among coffee drinkers, with quinic acid and its potential derivatives associated with both coffee and L asaccharolyticus.

IN PRACTICE:

“Our study provides insights into how the gut microbiome potentially mediates the chemistry — and thus health benefits — of coffee,” the study authors wrote. “The microbial mechanisms underlying the metabolism of coffee are a step towards mapping the role of specific foods on the gut microbiome, and similar patterns of microorganism–food interactions for other dietary elements should be sought with systematic epidemiologic and metagenomic investigations.”

SOURCE:

Paolo Manghi, PhD, University of Trento, Italy, led the study, which was published online in Nature Microbiology.

LIMITATIONS:

The authors relied on food questionnaires to assess coffee intake. The study is observational, and the clinical implications are unknown.

DISCLOSURES:

This work was supported by ZOE, a biotech company, and TwinsUK, an adult twin registry funded by the Wellcome Trust, Medical Research Council, Versus Arthritis, European Union Horizon 2020, Chronic Disease Research Foundation, the National Institute for Health and Care Research — Clinical Research Network and Biomedical Research Centre based at Guy’s and St. Thomas’ NHS Foundation Trust in partnership with King’s College London. Manghi had no competing interests. Several other coauthors reported financial relationships with ZOE, and three are cofounders of the company.

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

The Food and Drug Administration (FDA) has added a boxed warning about liver injury to fezolinetant (Veozah), a drug often prescribed for hot flashes in menopausal women, according to an FDA statement.

The warning is based on data from a postmarketing report of an individual who experienced elevated liver blood test values as well as symptoms of liver injury after approximately 40 days of taking fezolinetant, according to the statement.

The boxed warning is in addition to the existing warning about elevated liver blood test values and requirements for liver blood testing in the prescribing information.

The updated information also includes recommendations to increase the frequency of liver blood testing to monthly testing for 2 months after starting fezolinetant, then following the previous recommendations for testing at 3, 6, and 9 months.

In addition, the new information advises patients to discontinue the drug immediately and contact their prescribing healthcare professional if signs of liver injury occur, according to the statement. These signs may include nausea, vomiting, unusual itching, light-colored stool, jaundice, dark urine, abdominal swelling, or pain in the right upper abdomen.

The risk for liver injury is real, but rare, said Kathryn Marko, MD, assistant professor of obstetrics and gynecology at George Washington University, Washington, DC, in an interview.

Clinicians should advise patients that their liver function will be monitored closely if they take fezolinetant, Marko said. If elevations in liver function tests occur, they often return to normal after stopping the drug.

 

Clinical Implications and Research Gaps

The boxed warning may affect prescribing patterns in that patients or clinicians may fear the risk for liver injury, Marko said. “In addition, patients may be hesitant to start a medication that requires frequent blood test monitoring.” However, many alternative treatments are available for vasomotor symptoms of menopause, including hormonal and nonhormonal therapies, and patients and physicians should work together to come up with the best option for each individual.

“More research is needed to discover new therapies for menopause,” said Marko. “Veozah is unique in its mechanism of action, and it would be wonderful to see more new medications coming down the pipeline.”

Marko had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

The Food and Drug Administration (FDA) has added a boxed warning about liver injury to fezolinetant (Veozah), a drug often prescribed for hot flashes in menopausal women, according to an FDA statement.

The warning is based on data from a postmarketing report of an individual who experienced elevated liver blood test values as well as symptoms of liver injury after approximately 40 days of taking fezolinetant, according to the statement.

The boxed warning is in addition to the existing warning about elevated liver blood test values and requirements for liver blood testing in the prescribing information.

The updated information also includes recommendations to increase the frequency of liver blood testing to monthly testing for 2 months after starting fezolinetant, then following the previous recommendations for testing at 3, 6, and 9 months.

In addition, the new information advises patients to discontinue the drug immediately and contact their prescribing healthcare professional if signs of liver injury occur, according to the statement. These signs may include nausea, vomiting, unusual itching, light-colored stool, jaundice, dark urine, abdominal swelling, or pain in the right upper abdomen.

The risk for liver injury is real, but rare, said Kathryn Marko, MD, assistant professor of obstetrics and gynecology at George Washington University, Washington, DC, in an interview.

Clinicians should advise patients that their liver function will be monitored closely if they take fezolinetant, Marko said. If elevations in liver function tests occur, they often return to normal after stopping the drug.

 

Clinical Implications and Research Gaps

The boxed warning may affect prescribing patterns in that patients or clinicians may fear the risk for liver injury, Marko said. “In addition, patients may be hesitant to start a medication that requires frequent blood test monitoring.” However, many alternative treatments are available for vasomotor symptoms of menopause, including hormonal and nonhormonal therapies, and patients and physicians should work together to come up with the best option for each individual.

“More research is needed to discover new therapies for menopause,” said Marko. “Veozah is unique in its mechanism of action, and it would be wonderful to see more new medications coming down the pipeline.”

Marko had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

The Food and Drug Administration (FDA) has added a boxed warning about liver injury to fezolinetant (Veozah), a drug often prescribed for hot flashes in menopausal women, according to an FDA statement.

The warning is based on data from a postmarketing report of an individual who experienced elevated liver blood test values as well as symptoms of liver injury after approximately 40 days of taking fezolinetant, according to the statement.

The boxed warning is in addition to the existing warning about elevated liver blood test values and requirements for liver blood testing in the prescribing information.

The updated information also includes recommendations to increase the frequency of liver blood testing to monthly testing for 2 months after starting fezolinetant, then following the previous recommendations for testing at 3, 6, and 9 months.

In addition, the new information advises patients to discontinue the drug immediately and contact their prescribing healthcare professional if signs of liver injury occur, according to the statement. These signs may include nausea, vomiting, unusual itching, light-colored stool, jaundice, dark urine, abdominal swelling, or pain in the right upper abdomen.

The risk for liver injury is real, but rare, said Kathryn Marko, MD, assistant professor of obstetrics and gynecology at George Washington University, Washington, DC, in an interview.

Clinicians should advise patients that their liver function will be monitored closely if they take fezolinetant, Marko said. If elevations in liver function tests occur, they often return to normal after stopping the drug.

 

Clinical Implications and Research Gaps

The boxed warning may affect prescribing patterns in that patients or clinicians may fear the risk for liver injury, Marko said. “In addition, patients may be hesitant to start a medication that requires frequent blood test monitoring.” However, many alternative treatments are available for vasomotor symptoms of menopause, including hormonal and nonhormonal therapies, and patients and physicians should work together to come up with the best option for each individual.

“More research is needed to discover new therapies for menopause,” said Marko. “Veozah is unique in its mechanism of action, and it would be wonderful to see more new medications coming down the pipeline.”

Marko had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

For almost 2 decades, antidepressants have carried boxed warnings linking the medications to an increased risk for suicidal thoughts and behaviors in young people. Paradoxically, and for almost as long, evidence suggests these warnings may have led to fewer depression diagnoses, reduced prescriptions, and, ultimately, higher suicide rates.

With mounting evidence of these negative unintended consequences, some clinicians and researchers are urging the Food and Drug Administration (FDA) to consider revising — or even eliminating — boxed warnings on these medications.

The latest report challenging the utility of the 2005 warnings was particularly sobering. Published in October in Health Affairs, the systematic review of studies from 2003 to 2022 showed a 20%-40% decline in physician visits for depression, a 20%-50% decline in antidepressant use, and an abrupt increase in psychotropic drug poisonings and suicides — all after the warnings were added.

“FDA officials should review the totality of evidence and err on the side of caution in acknowledging possible harms of the antidepressant warnings,” lead author Stephen Soumerai, ScD, professor of population medicine at Harvard Medical School at Harvard Pilgrim Health Care Institute, Boston, Massachusetts and colleagues wrote. They called on the FDA to replace the boxed warnings with a routine warning in labeling.

While good prospective data on the risks and benefits of antidepressants in youth were limited when the boxed warnings were instituted, there is more information now, said Jeffrey Strawn, MD, professor of psychiatry and pediatrics at the University of Cincinnati College of Medicine in Ohio. Strawn, whose research on the topic has been cited frequently over the years, said the new evidence suggests it is time for the FDA to reevaluate the warnings.

“I don’t think that they’ve been useful. They’ve actually been harmful,” Strawn told this news organization. “These boxed warnings have decreased physicians’ and other clinicians’ comfort and tendency to prescribe.”

 

Decline in Diagnoses

The FDA issued its first warning about the potential for suicidal thoughts and behavior in children in 2003. After an advisory panel weighed the evidence, the agency added a boxed warning in 2005 to all antidepressants for children younger than 18 years. The warning was expanded in 2007 to include young adults through age 24.

Data suggesting that the warnings have had unintended effects can be found going back to just after they were issued. For instance, in 2009, after rising for years, the rate of new pediatric depression diagnoses fell precipitously after the warning was added, with primary care physicians diagnosing 44% fewer cases.

In 2014, citing evidence of fewer diagnoses and rising psychotropic drug poisonings, Weill Cornell Medicine Professor Richard A. Friedman, MD, called on the FDA in a perspective to remove the boxed warnings.

Strawn and colleagues reported in an often-cited 2014 systematic review and meta-analysis that, in nine trials involving 1673 patients and six medications, antidepressants were superior to placebo, with no increased risk for suicidal thoughts or behavior.

He has also studied adverse effects of the medications, reporting in Pharmacotherapy that suicidality risk might be more likely with some medications, such as paroxetine and venlafaxine, and that it could be influenced by baseline suicidality, among many other factors. A Swedish register study found that risk was highest the month before starting a medication, Strawn and colleagues wrote.

Dara Sakolsky, MD, PhD, associate professor of psychiatry and associate medical director, Services for Teens at Risk at the University of Pittsburgh School of Medicine, Pennsylvania, told this news organization that, because of “these negative unintended consequences,” the FDA should lower the temperature by putting the warnings in labeling.

“It makes sense based on the data that we have at hand now,” said Sakolsky.

 

The Dangers of Untreated Depression

Even with this new information, lingering concerns about earlier studies that pointed to increased suicidality risk may discourage prescribing by primary care physicians and pediatricians, and that worries researchers and psychiatrists.

“My concern is that the risk for suicide and suicidal behavior may be higher in untreated depression than the risk of suicidal thoughts or behaviors from antidepressants,” Jeffrey Bridge, PhD, director of the Center for Suicide Prevention and Research at Nationwide Children’s Hospital, Columbus, Ohio, told this news organization.

Bridge is the lead author of a much-cited 2007 meta-analysis in JAMA that showed that the benefits of antidepressants in children and adolescents appeared to be greater than the risks for suicidality. “The concern about antidepressants must be considered in the context of possible benefit,” wrote Bridge, who also is professor of pediatrics, psychiatry, and behavioral health at Ohio State University College of Medicine, Columbus.

Depression and suicide are a scourge for those younger than 25 years. A 2021 literature review noted that the prevalence of depression — which has been increasing for all Americans — has risen more among adolescents than adults. Depression is “strongly associated with suicide,” the authors wrote.

In 2021, the National Institute of Mental Health reported suicide was the second leading cause of death among 10- to 14-year-olds and the third leading cause of death among those aged 15-24 years.

Suicide kills more kids aged between 10 and 24 years than cancer and all other illnesses combined, John Campo, MD, director of child and adolescent psychiatry at Johns Hopkins University School of Medicine and vice president of psychiatric services at Kennedy Krieger Institute, told this news organization.

Meanwhile, he added, the medications work and clinicians balance risk and benefit in prescribing.

The landmark 2007 Treatment for Adolescents with Depression Study showed that fluoxetine, especially in combination with cognitive-behavioral therapy (CBT), was significantly better than placebo. Since that time, legions of trials have shown the drugs’ effectiveness.

The most effective treatment for teen depression is a combination of CBT and a selective serotonin reuptake inhibitor, said Sakolsky.

“We know that the evidence for that is pretty good,” she said. “On the flip side, we know the risk of having an adverse outcome is pretty low.”

Sakolsky tells patients and families that perhaps 1 in 146 will have a suicidal thought or behavior. “That’s pretty rare when we know how effective these medicines are.” 

Strawn said he always notes that no suicides took place in the trials that led to the warning and stresses that he closely monitors patients. “While the more recent prospective data are reassuring,” the suicidality risk “is something that we still talk about,” he said. He also discusses how some antidepressants seem to increase risk more than others.

For Campo, the discussion is based on his reading of the evidence, not the presence of the FDA warning.

“Based on what we know, I still think it’s fair to proceed with the idea that there is a small, but real risk,” he said. However, “at the same time, the medications might be exceptionally helpful for some kids.”

 

‘What Do We Do Now?’

When the FDA issued its warning in 2005, the agency said it identified the risk for suicidality in a combined analysis of short-term placebo-controlled trials of nine antidepressants. It ultimately included 24 trials involving more than 4400 patients. The risk was highest in the first few months. The average risk for those taking antidepressants was 4%, twice the placebo risk of 2%. There were no suicides in these trials, however.

The trials relied on spontaneous reports of adverse events, not predetermined measures, Campo said. Even so, that 2% difference is “nothing to sneeze at,” he noted.

Bridge’s meta-analysis showed a smaller difference — closer to 0.7%. “But it was still statistically significant,” Campo said. “I have trouble ignoring that.”

The unintended consequences of the warning can’t be studied in a randomized controlled trial. Studies have shown an association but not a direct cause-and-effect relationship between the warning and a decline in treatment and rise in suicides.

But the potential for suicidal thoughts and behavior with antidepressants has been studied prospectively. Some older studies found a significant risk, while more recent trials have not.

While the Health Affairs analysis “certainly makes a strong case,” it is observational data, Campo said.

“The question is, what do we do now in retrospect? Do you say, ‘Never mind. We don’t need the black box warning anymore?’ ” he said. “That would require a pretty careful look.”

The Health Affairs paper “makes me think that there are other areas of research that that need to be completed and done and updated, and then there should be an assessment, a reevaluation from the FDA,” said Bridge. A new meta-analysis “would be very informative,” he said.

 

What’s Next?

When asked about the Health Affairs paper and whether the agency would review the warnings, an FDA spokesperson told this news organization that the agency “does not comment on specific studies but evaluates them as part of the body of evidence to further our understanding about a particular issue and assist in our mission to protect public health.”

Sakolsky said the data clearly point to the damage that the warning has done over the past 2 decades, but that things might be improving. Studies conducted more recently might not have captured some changes in practice.

For instance, she noted, in 2022, the US Preventive Services Task Force recommended screening for major depressive disorder in adolescents aged 12-18 years. In turn, she has seen more patients in her office who were referred by pediatricians who had conducted the screening, said Sakolsky.

Strawn said the time for pontificating is long past due. “We’re withholding medications and other treatments that could potentially be effective for disorders that, in and of themselves, are associated with a significant increase in the risk of suicide.” 

After the FDA instituted the warning, “we were all very nervous,” about the potential fallout, said Campo, adding that a part of him wishes that the warnings had been “more mundane and less dramatic.”

Despite the unintended consequences, “it’s going to be hard to put the genie back in the bottle,” he said.

Campo and Sakolsky reported no relevant financial relationships. Strawn disclosed that his institution has received research funding from the National Institute of Child Health and Human Development, the Patient-Centered Outcomes Research Institute (PCORI), and AbbVie. Bridge reported that he received grant support from the National Institute of Mental Health, Centers for Disease Control and Prevention, and PCORI; is a scientific adviser to Clarigent Health; and is on the Scientific Council of the American Foundation for Suicide Prevention.

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

For almost 2 decades, antidepressants have carried boxed warnings linking the medications to an increased risk for suicidal thoughts and behaviors in young people. Paradoxically, and for almost as long, evidence suggests these warnings may have led to fewer depression diagnoses, reduced prescriptions, and, ultimately, higher suicide rates.

With mounting evidence of these negative unintended consequences, some clinicians and researchers are urging the Food and Drug Administration (FDA) to consider revising — or even eliminating — boxed warnings on these medications.

The latest report challenging the utility of the 2005 warnings was particularly sobering. Published in October in Health Affairs, the systematic review of studies from 2003 to 2022 showed a 20%-40% decline in physician visits for depression, a 20%-50% decline in antidepressant use, and an abrupt increase in psychotropic drug poisonings and suicides — all after the warnings were added.

“FDA officials should review the totality of evidence and err on the side of caution in acknowledging possible harms of the antidepressant warnings,” lead author Stephen Soumerai, ScD, professor of population medicine at Harvard Medical School at Harvard Pilgrim Health Care Institute, Boston, Massachusetts and colleagues wrote. They called on the FDA to replace the boxed warnings with a routine warning in labeling.

While good prospective data on the risks and benefits of antidepressants in youth were limited when the boxed warnings were instituted, there is more information now, said Jeffrey Strawn, MD, professor of psychiatry and pediatrics at the University of Cincinnati College of Medicine in Ohio. Strawn, whose research on the topic has been cited frequently over the years, said the new evidence suggests it is time for the FDA to reevaluate the warnings.

“I don’t think that they’ve been useful. They’ve actually been harmful,” Strawn told this news organization. “These boxed warnings have decreased physicians’ and other clinicians’ comfort and tendency to prescribe.”

 

Decline in Diagnoses

The FDA issued its first warning about the potential for suicidal thoughts and behavior in children in 2003. After an advisory panel weighed the evidence, the agency added a boxed warning in 2005 to all antidepressants for children younger than 18 years. The warning was expanded in 2007 to include young adults through age 24.

Data suggesting that the warnings have had unintended effects can be found going back to just after they were issued. For instance, in 2009, after rising for years, the rate of new pediatric depression diagnoses fell precipitously after the warning was added, with primary care physicians diagnosing 44% fewer cases.

In 2014, citing evidence of fewer diagnoses and rising psychotropic drug poisonings, Weill Cornell Medicine Professor Richard A. Friedman, MD, called on the FDA in a perspective to remove the boxed warnings.

Strawn and colleagues reported in an often-cited 2014 systematic review and meta-analysis that, in nine trials involving 1673 patients and six medications, antidepressants were superior to placebo, with no increased risk for suicidal thoughts or behavior.

He has also studied adverse effects of the medications, reporting in Pharmacotherapy that suicidality risk might be more likely with some medications, such as paroxetine and venlafaxine, and that it could be influenced by baseline suicidality, among many other factors. A Swedish register study found that risk was highest the month before starting a medication, Strawn and colleagues wrote.

Dara Sakolsky, MD, PhD, associate professor of psychiatry and associate medical director, Services for Teens at Risk at the University of Pittsburgh School of Medicine, Pennsylvania, told this news organization that, because of “these negative unintended consequences,” the FDA should lower the temperature by putting the warnings in labeling.

“It makes sense based on the data that we have at hand now,” said Sakolsky.

 

The Dangers of Untreated Depression

Even with this new information, lingering concerns about earlier studies that pointed to increased suicidality risk may discourage prescribing by primary care physicians and pediatricians, and that worries researchers and psychiatrists.

“My concern is that the risk for suicide and suicidal behavior may be higher in untreated depression than the risk of suicidal thoughts or behaviors from antidepressants,” Jeffrey Bridge, PhD, director of the Center for Suicide Prevention and Research at Nationwide Children’s Hospital, Columbus, Ohio, told this news organization.

Bridge is the lead author of a much-cited 2007 meta-analysis in JAMA that showed that the benefits of antidepressants in children and adolescents appeared to be greater than the risks for suicidality. “The concern about antidepressants must be considered in the context of possible benefit,” wrote Bridge, who also is professor of pediatrics, psychiatry, and behavioral health at Ohio State University College of Medicine, Columbus.

Depression and suicide are a scourge for those younger than 25 years. A 2021 literature review noted that the prevalence of depression — which has been increasing for all Americans — has risen more among adolescents than adults. Depression is “strongly associated with suicide,” the authors wrote.

In 2021, the National Institute of Mental Health reported suicide was the second leading cause of death among 10- to 14-year-olds and the third leading cause of death among those aged 15-24 years.

Suicide kills more kids aged between 10 and 24 years than cancer and all other illnesses combined, John Campo, MD, director of child and adolescent psychiatry at Johns Hopkins University School of Medicine and vice president of psychiatric services at Kennedy Krieger Institute, told this news organization.

Meanwhile, he added, the medications work and clinicians balance risk and benefit in prescribing.

The landmark 2007 Treatment for Adolescents with Depression Study showed that fluoxetine, especially in combination with cognitive-behavioral therapy (CBT), was significantly better than placebo. Since that time, legions of trials have shown the drugs’ effectiveness.

The most effective treatment for teen depression is a combination of CBT and a selective serotonin reuptake inhibitor, said Sakolsky.

“We know that the evidence for that is pretty good,” she said. “On the flip side, we know the risk of having an adverse outcome is pretty low.”

Sakolsky tells patients and families that perhaps 1 in 146 will have a suicidal thought or behavior. “That’s pretty rare when we know how effective these medicines are.” 

Strawn said he always notes that no suicides took place in the trials that led to the warning and stresses that he closely monitors patients. “While the more recent prospective data are reassuring,” the suicidality risk “is something that we still talk about,” he said. He also discusses how some antidepressants seem to increase risk more than others.

For Campo, the discussion is based on his reading of the evidence, not the presence of the FDA warning.

“Based on what we know, I still think it’s fair to proceed with the idea that there is a small, but real risk,” he said. However, “at the same time, the medications might be exceptionally helpful for some kids.”

 

‘What Do We Do Now?’

When the FDA issued its warning in 2005, the agency said it identified the risk for suicidality in a combined analysis of short-term placebo-controlled trials of nine antidepressants. It ultimately included 24 trials involving more than 4400 patients. The risk was highest in the first few months. The average risk for those taking antidepressants was 4%, twice the placebo risk of 2%. There were no suicides in these trials, however.

The trials relied on spontaneous reports of adverse events, not predetermined measures, Campo said. Even so, that 2% difference is “nothing to sneeze at,” he noted.

Bridge’s meta-analysis showed a smaller difference — closer to 0.7%. “But it was still statistically significant,” Campo said. “I have trouble ignoring that.”

The unintended consequences of the warning can’t be studied in a randomized controlled trial. Studies have shown an association but not a direct cause-and-effect relationship between the warning and a decline in treatment and rise in suicides.

But the potential for suicidal thoughts and behavior with antidepressants has been studied prospectively. Some older studies found a significant risk, while more recent trials have not.

While the Health Affairs analysis “certainly makes a strong case,” it is observational data, Campo said.

“The question is, what do we do now in retrospect? Do you say, ‘Never mind. We don’t need the black box warning anymore?’ ” he said. “That would require a pretty careful look.”

The Health Affairs paper “makes me think that there are other areas of research that that need to be completed and done and updated, and then there should be an assessment, a reevaluation from the FDA,” said Bridge. A new meta-analysis “would be very informative,” he said.

 

What’s Next?

When asked about the Health Affairs paper and whether the agency would review the warnings, an FDA spokesperson told this news organization that the agency “does not comment on specific studies but evaluates them as part of the body of evidence to further our understanding about a particular issue and assist in our mission to protect public health.”

Sakolsky said the data clearly point to the damage that the warning has done over the past 2 decades, but that things might be improving. Studies conducted more recently might not have captured some changes in practice.

For instance, she noted, in 2022, the US Preventive Services Task Force recommended screening for major depressive disorder in adolescents aged 12-18 years. In turn, she has seen more patients in her office who were referred by pediatricians who had conducted the screening, said Sakolsky.

Strawn said the time for pontificating is long past due. “We’re withholding medications and other treatments that could potentially be effective for disorders that, in and of themselves, are associated with a significant increase in the risk of suicide.” 

After the FDA instituted the warning, “we were all very nervous,” about the potential fallout, said Campo, adding that a part of him wishes that the warnings had been “more mundane and less dramatic.”

Despite the unintended consequences, “it’s going to be hard to put the genie back in the bottle,” he said.

Campo and Sakolsky reported no relevant financial relationships. Strawn disclosed that his institution has received research funding from the National Institute of Child Health and Human Development, the Patient-Centered Outcomes Research Institute (PCORI), and AbbVie. Bridge reported that he received grant support from the National Institute of Mental Health, Centers for Disease Control and Prevention, and PCORI; is a scientific adviser to Clarigent Health; and is on the Scientific Council of the American Foundation for Suicide Prevention.

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

For almost 2 decades, antidepressants have carried boxed warnings linking the medications to an increased risk for suicidal thoughts and behaviors in young people. Paradoxically, and for almost as long, evidence suggests these warnings may have led to fewer depression diagnoses, reduced prescriptions, and, ultimately, higher suicide rates.

With mounting evidence of these negative unintended consequences, some clinicians and researchers are urging the Food and Drug Administration (FDA) to consider revising — or even eliminating — boxed warnings on these medications.

The latest report challenging the utility of the 2005 warnings was particularly sobering. Published in October in Health Affairs, the systematic review of studies from 2003 to 2022 showed a 20%-40% decline in physician visits for depression, a 20%-50% decline in antidepressant use, and an abrupt increase in psychotropic drug poisonings and suicides — all after the warnings were added.

“FDA officials should review the totality of evidence and err on the side of caution in acknowledging possible harms of the antidepressant warnings,” lead author Stephen Soumerai, ScD, professor of population medicine at Harvard Medical School at Harvard Pilgrim Health Care Institute, Boston, Massachusetts and colleagues wrote. They called on the FDA to replace the boxed warnings with a routine warning in labeling.

While good prospective data on the risks and benefits of antidepressants in youth were limited when the boxed warnings were instituted, there is more information now, said Jeffrey Strawn, MD, professor of psychiatry and pediatrics at the University of Cincinnati College of Medicine in Ohio. Strawn, whose research on the topic has been cited frequently over the years, said the new evidence suggests it is time for the FDA to reevaluate the warnings.

“I don’t think that they’ve been useful. They’ve actually been harmful,” Strawn told this news organization. “These boxed warnings have decreased physicians’ and other clinicians’ comfort and tendency to prescribe.”

 

Decline in Diagnoses

The FDA issued its first warning about the potential for suicidal thoughts and behavior in children in 2003. After an advisory panel weighed the evidence, the agency added a boxed warning in 2005 to all antidepressants for children younger than 18 years. The warning was expanded in 2007 to include young adults through age 24.

Data suggesting that the warnings have had unintended effects can be found going back to just after they were issued. For instance, in 2009, after rising for years, the rate of new pediatric depression diagnoses fell precipitously after the warning was added, with primary care physicians diagnosing 44% fewer cases.

In 2014, citing evidence of fewer diagnoses and rising psychotropic drug poisonings, Weill Cornell Medicine Professor Richard A. Friedman, MD, called on the FDA in a perspective to remove the boxed warnings.

Strawn and colleagues reported in an often-cited 2014 systematic review and meta-analysis that, in nine trials involving 1673 patients and six medications, antidepressants were superior to placebo, with no increased risk for suicidal thoughts or behavior.

He has also studied adverse effects of the medications, reporting in Pharmacotherapy that suicidality risk might be more likely with some medications, such as paroxetine and venlafaxine, and that it could be influenced by baseline suicidality, among many other factors. A Swedish register study found that risk was highest the month before starting a medication, Strawn and colleagues wrote.

Dara Sakolsky, MD, PhD, associate professor of psychiatry and associate medical director, Services for Teens at Risk at the University of Pittsburgh School of Medicine, Pennsylvania, told this news organization that, because of “these negative unintended consequences,” the FDA should lower the temperature by putting the warnings in labeling.

“It makes sense based on the data that we have at hand now,” said Sakolsky.

 

The Dangers of Untreated Depression

Even with this new information, lingering concerns about earlier studies that pointed to increased suicidality risk may discourage prescribing by primary care physicians and pediatricians, and that worries researchers and psychiatrists.

“My concern is that the risk for suicide and suicidal behavior may be higher in untreated depression than the risk of suicidal thoughts or behaviors from antidepressants,” Jeffrey Bridge, PhD, director of the Center for Suicide Prevention and Research at Nationwide Children’s Hospital, Columbus, Ohio, told this news organization.

Bridge is the lead author of a much-cited 2007 meta-analysis in JAMA that showed that the benefits of antidepressants in children and adolescents appeared to be greater than the risks for suicidality. “The concern about antidepressants must be considered in the context of possible benefit,” wrote Bridge, who also is professor of pediatrics, psychiatry, and behavioral health at Ohio State University College of Medicine, Columbus.

Depression and suicide are a scourge for those younger than 25 years. A 2021 literature review noted that the prevalence of depression — which has been increasing for all Americans — has risen more among adolescents than adults. Depression is “strongly associated with suicide,” the authors wrote.

In 2021, the National Institute of Mental Health reported suicide was the second leading cause of death among 10- to 14-year-olds and the third leading cause of death among those aged 15-24 years.

Suicide kills more kids aged between 10 and 24 years than cancer and all other illnesses combined, John Campo, MD, director of child and adolescent psychiatry at Johns Hopkins University School of Medicine and vice president of psychiatric services at Kennedy Krieger Institute, told this news organization.

Meanwhile, he added, the medications work and clinicians balance risk and benefit in prescribing.

The landmark 2007 Treatment for Adolescents with Depression Study showed that fluoxetine, especially in combination with cognitive-behavioral therapy (CBT), was significantly better than placebo. Since that time, legions of trials have shown the drugs’ effectiveness.

The most effective treatment for teen depression is a combination of CBT and a selective serotonin reuptake inhibitor, said Sakolsky.

“We know that the evidence for that is pretty good,” she said. “On the flip side, we know the risk of having an adverse outcome is pretty low.”

Sakolsky tells patients and families that perhaps 1 in 146 will have a suicidal thought or behavior. “That’s pretty rare when we know how effective these medicines are.” 

Strawn said he always notes that no suicides took place in the trials that led to the warning and stresses that he closely monitors patients. “While the more recent prospective data are reassuring,” the suicidality risk “is something that we still talk about,” he said. He also discusses how some antidepressants seem to increase risk more than others.

For Campo, the discussion is based on his reading of the evidence, not the presence of the FDA warning.

“Based on what we know, I still think it’s fair to proceed with the idea that there is a small, but real risk,” he said. However, “at the same time, the medications might be exceptionally helpful for some kids.”

 

‘What Do We Do Now?’

When the FDA issued its warning in 2005, the agency said it identified the risk for suicidality in a combined analysis of short-term placebo-controlled trials of nine antidepressants. It ultimately included 24 trials involving more than 4400 patients. The risk was highest in the first few months. The average risk for those taking antidepressants was 4%, twice the placebo risk of 2%. There were no suicides in these trials, however.

The trials relied on spontaneous reports of adverse events, not predetermined measures, Campo said. Even so, that 2% difference is “nothing to sneeze at,” he noted.

Bridge’s meta-analysis showed a smaller difference — closer to 0.7%. “But it was still statistically significant,” Campo said. “I have trouble ignoring that.”

The unintended consequences of the warning can’t be studied in a randomized controlled trial. Studies have shown an association but not a direct cause-and-effect relationship between the warning and a decline in treatment and rise in suicides.

But the potential for suicidal thoughts and behavior with antidepressants has been studied prospectively. Some older studies found a significant risk, while more recent trials have not.

While the Health Affairs analysis “certainly makes a strong case,” it is observational data, Campo said.

“The question is, what do we do now in retrospect? Do you say, ‘Never mind. We don’t need the black box warning anymore?’ ” he said. “That would require a pretty careful look.”

The Health Affairs paper “makes me think that there are other areas of research that that need to be completed and done and updated, and then there should be an assessment, a reevaluation from the FDA,” said Bridge. A new meta-analysis “would be very informative,” he said.

 

What’s Next?

When asked about the Health Affairs paper and whether the agency would review the warnings, an FDA spokesperson told this news organization that the agency “does not comment on specific studies but evaluates them as part of the body of evidence to further our understanding about a particular issue and assist in our mission to protect public health.”

Sakolsky said the data clearly point to the damage that the warning has done over the past 2 decades, but that things might be improving. Studies conducted more recently might not have captured some changes in practice.

For instance, she noted, in 2022, the US Preventive Services Task Force recommended screening for major depressive disorder in adolescents aged 12-18 years. In turn, she has seen more patients in her office who were referred by pediatricians who had conducted the screening, said Sakolsky.

Strawn said the time for pontificating is long past due. “We’re withholding medications and other treatments that could potentially be effective for disorders that, in and of themselves, are associated with a significant increase in the risk of suicide.” 

After the FDA instituted the warning, “we were all very nervous,” about the potential fallout, said Campo, adding that a part of him wishes that the warnings had been “more mundane and less dramatic.”

Despite the unintended consequences, “it’s going to be hard to put the genie back in the bottle,” he said.

Campo and Sakolsky reported no relevant financial relationships. Strawn disclosed that his institution has received research funding from the National Institute of Child Health and Human Development, the Patient-Centered Outcomes Research Institute (PCORI), and AbbVie. Bridge reported that he received grant support from the National Institute of Mental Health, Centers for Disease Control and Prevention, and PCORI; is a scientific adviser to Clarigent Health; and is on the Scientific Council of the American Foundation for Suicide Prevention.

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

TOPLINE:

Age-standardized mortality rates for hepatocellular carcinoma (HCC) in the United States are expected to rise from 5.03 per 100,000 persons in 2022 to 6.39 per 100,000 persons by 2040. Alcohol-associated liver disease (ALD) will likely become the leading cause of HCC-related mortality by 2026, and metabolic dysfunction–associated steatotic liver disease (MASLD) is projected to become the second leading cause by 2032, a new analysis found. 

METHODOLOGY:

• HCC accounts for 75%-85% of primary liver cancers and most liver cancer deaths. Researchers have observed an upward trend in the incidence of and mortality from HCC in the past 2 decades.
• This cross-sectional study analyzed 188,280 HCC-related deaths among adults aged 25 and older to determine trends in mortality rates and project age-standardized mortality rates through 2040. Data came from the National Vital Statistics System database from 2006 to 2022.
• Researchers stratified mortality data by etiology of liver disease (ALD, hepatitis B virus, hepatitis C virus, and MASLD), age groups (25-64 or 65 and older years), sex, and race/ethnicity.
• Demographic data showed that 77.4% of deaths occurred in men, 55.6% in individuals aged 65 years or older, and 62.3% in White individuals.

TAKEAWAY:

• Overall, the age-standardized mortality rate for HCC-related deaths increased from 3.65 per 100,000 persons in 2006 to 5.03 in 2022 and was projected to increase to 6.39 per 100,000 persons by 2040.
• Sex- and age-related disparities were substantial. Men had much higher rates of HCC-related mortality than women (8.15 vs 2.33 per 100,000 persons), with a projected rate among men of 9.78 per 100,000 persons by 2040. HCC-related mortality rates for people aged 65 years or older were 10 times higher than for those aged 25-64 years (18.37 vs 1.79 per 100,000 persons) in 2022 and was projected to reach 32.81 per 100,000 persons by 2040 in the older group.
• Although hepatitis C virus–related deaths were projected to decline from 0.69 to 0.03 per 100,000 persons by 2034, ALD- and MASLD-related deaths showed increasing trends, with both projected to become the two leading causes of HCC-related mortality in the next few years.
• Racial disparities were also evident. By 2040, the American Indian/Alaska Native population showed the highest increase in projected HCC-related mortality rates, which went from 5.46 per 100,000 persons in 2006 to a project increase to 14.71 per 100,000 persons.

IN PRACTICE:

“HCC mortality was projected to continue increasing in the US, primarily due to rising rates of deaths attributable to ALD and MASLD,” the authors wrote. 

This “study highlights the importance of addressing these conditions to decrease the burden of liver disease and liver disease mortality in the future,” Emad Qayed, MD, MPH, Emory University School of Medicine, Atlanta, wrote in an accompanying editorial.

SOURCE:

The study was led by Sikai Qiu, MM, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China, and was published online in JAMA Network Open.
 

LIMITATIONS:

The National Vital Statistics System database used in this study captured only mortality data without access to detailed clinical records or individual medical histories. Researchers could not analyze socioeconomic factors or individual-level risk factors owing to data anonymization requirements. Additionally, the inclusion of the COVID-19 pandemic period could have influenced observed trends and reliability of future projections.
 

DISCLOSURES:

This study was supported by grants from the National Natural Science Foundation of China. Several authors reported receiving consulting fees, speaking fees, or research support from various sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Age-standardized mortality rates for hepatocellular carcinoma (HCC) in the United States are expected to rise from 5.03 per 100,000 persons in 2022 to 6.39 per 100,000 persons by 2040. Alcohol-associated liver disease (ALD) will likely become the leading cause of HCC-related mortality by 2026, and metabolic dysfunction–associated steatotic liver disease (MASLD) is projected to become the second leading cause by 2032, a new analysis found. 

METHODOLOGY:

• HCC accounts for 75%-85% of primary liver cancers and most liver cancer deaths. Researchers have observed an upward trend in the incidence of and mortality from HCC in the past 2 decades.
• This cross-sectional study analyzed 188,280 HCC-related deaths among adults aged 25 and older to determine trends in mortality rates and project age-standardized mortality rates through 2040. Data came from the National Vital Statistics System database from 2006 to 2022.
• Researchers stratified mortality data by etiology of liver disease (ALD, hepatitis B virus, hepatitis C virus, and MASLD), age groups (25-64 or 65 and older years), sex, and race/ethnicity.
• Demographic data showed that 77.4% of deaths occurred in men, 55.6% in individuals aged 65 years or older, and 62.3% in White individuals.

TAKEAWAY:

• Overall, the age-standardized mortality rate for HCC-related deaths increased from 3.65 per 100,000 persons in 2006 to 5.03 in 2022 and was projected to increase to 6.39 per 100,000 persons by 2040.
• Sex- and age-related disparities were substantial. Men had much higher rates of HCC-related mortality than women (8.15 vs 2.33 per 100,000 persons), with a projected rate among men of 9.78 per 100,000 persons by 2040. HCC-related mortality rates for people aged 65 years or older were 10 times higher than for those aged 25-64 years (18.37 vs 1.79 per 100,000 persons) in 2022 and was projected to reach 32.81 per 100,000 persons by 2040 in the older group.
• Although hepatitis C virus–related deaths were projected to decline from 0.69 to 0.03 per 100,000 persons by 2034, ALD- and MASLD-related deaths showed increasing trends, with both projected to become the two leading causes of HCC-related mortality in the next few years.
• Racial disparities were also evident. By 2040, the American Indian/Alaska Native population showed the highest increase in projected HCC-related mortality rates, which went from 5.46 per 100,000 persons in 2006 to a project increase to 14.71 per 100,000 persons.

IN PRACTICE:

“HCC mortality was projected to continue increasing in the US, primarily due to rising rates of deaths attributable to ALD and MASLD,” the authors wrote. 

This “study highlights the importance of addressing these conditions to decrease the burden of liver disease and liver disease mortality in the future,” Emad Qayed, MD, MPH, Emory University School of Medicine, Atlanta, wrote in an accompanying editorial.

SOURCE:

The study was led by Sikai Qiu, MM, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China, and was published online in JAMA Network Open.
 

LIMITATIONS:

The National Vital Statistics System database used in this study captured only mortality data without access to detailed clinical records or individual medical histories. Researchers could not analyze socioeconomic factors or individual-level risk factors owing to data anonymization requirements. Additionally, the inclusion of the COVID-19 pandemic period could have influenced observed trends and reliability of future projections.
 

DISCLOSURES:

This study was supported by grants from the National Natural Science Foundation of China. Several authors reported receiving consulting fees, speaking fees, or research support from various sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Age-standardized mortality rates for hepatocellular carcinoma (HCC) in the United States are expected to rise from 5.03 per 100,000 persons in 2022 to 6.39 per 100,000 persons by 2040. Alcohol-associated liver disease (ALD) will likely become the leading cause of HCC-related mortality by 2026, and metabolic dysfunction–associated steatotic liver disease (MASLD) is projected to become the second leading cause by 2032, a new analysis found. 

METHODOLOGY:

• HCC accounts for 75%-85% of primary liver cancers and most liver cancer deaths. Researchers have observed an upward trend in the incidence of and mortality from HCC in the past 2 decades.
• This cross-sectional study analyzed 188,280 HCC-related deaths among adults aged 25 and older to determine trends in mortality rates and project age-standardized mortality rates through 2040. Data came from the National Vital Statistics System database from 2006 to 2022.
• Researchers stratified mortality data by etiology of liver disease (ALD, hepatitis B virus, hepatitis C virus, and MASLD), age groups (25-64 or 65 and older years), sex, and race/ethnicity.
• Demographic data showed that 77.4% of deaths occurred in men, 55.6% in individuals aged 65 years or older, and 62.3% in White individuals.

TAKEAWAY:

• Overall, the age-standardized mortality rate for HCC-related deaths increased from 3.65 per 100,000 persons in 2006 to 5.03 in 2022 and was projected to increase to 6.39 per 100,000 persons by 2040.
• Sex- and age-related disparities were substantial. Men had much higher rates of HCC-related mortality than women (8.15 vs 2.33 per 100,000 persons), with a projected rate among men of 9.78 per 100,000 persons by 2040. HCC-related mortality rates for people aged 65 years or older were 10 times higher than for those aged 25-64 years (18.37 vs 1.79 per 100,000 persons) in 2022 and was projected to reach 32.81 per 100,000 persons by 2040 in the older group.
• Although hepatitis C virus–related deaths were projected to decline from 0.69 to 0.03 per 100,000 persons by 2034, ALD- and MASLD-related deaths showed increasing trends, with both projected to become the two leading causes of HCC-related mortality in the next few years.
• Racial disparities were also evident. By 2040, the American Indian/Alaska Native population showed the highest increase in projected HCC-related mortality rates, which went from 5.46 per 100,000 persons in 2006 to a project increase to 14.71 per 100,000 persons.

IN PRACTICE:

“HCC mortality was projected to continue increasing in the US, primarily due to rising rates of deaths attributable to ALD and MASLD,” the authors wrote. 

This “study highlights the importance of addressing these conditions to decrease the burden of liver disease and liver disease mortality in the future,” Emad Qayed, MD, MPH, Emory University School of Medicine, Atlanta, wrote in an accompanying editorial.

SOURCE:

The study was led by Sikai Qiu, MM, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China, and was published online in JAMA Network Open.
 

LIMITATIONS:

The National Vital Statistics System database used in this study captured only mortality data without access to detailed clinical records or individual medical histories. Researchers could not analyze socioeconomic factors or individual-level risk factors owing to data anonymization requirements. Additionally, the inclusion of the COVID-19 pandemic period could have influenced observed trends and reliability of future projections.
 

DISCLOSURES:

This study was supported by grants from the National Natural Science Foundation of China. Several authors reported receiving consulting fees, speaking fees, or research support from various sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

An individual’s estimated risk of having a heart attack or stroke in the next 10 years is widely used to guide preventative medication prescriptions with statins or antihypertensive drugs in those who have not yet had such an event.

To estimate that risk, doctors use equations that include different risk factors, such as age, cholesterol levels, and blood pressure. The current equations, known as the pooled cohort equations, are considered to be outdated as they were developed in 2013 based on population data from the 1960s and 70s. A new set of risk equations — known as the PREVENT equations — were developed by the American Heart Association (AHA) in 2023, and are based on a more contemporary population. It is anticipated that AHA will recommend these new risk equations be used in clinical practice in the next primary prevention guidelines.

But could these new risk equations do more harm than good?

Two recent studies found that applying the PREVENT risk equations to the US population results in a much lower overall level of risk compared with the pooled cohort equations. And, if the current threshold for starting statin treatment — which is an estimated 7.5% risk of having a heart attack or stroke in the next 10 years — is kept the same, this would result in many fewer patients being eligible for statin treatment.

As cardiovascular risk is also used to guide antihypertensive treatment, the new risk equations would also result in fewer people with borderline high blood pressure being eligible for those medications.

This has raised concerns in the medical community, where there is a widespread view that many more people would benefit from primary prevention treatment, and that anything that may cause fewer people to receive these medications would be harmful. 

“I believe the new equations more accurately predict the risk of the current US population, but we need to be aware of what effect that may have on use of statins,” said Tim Anderson, MD, who studies healthcare delivery at the University of Pittsburgh in Pennsylvania and is lead author of one of the studies evaluating the equations.

Anderson told this news organization that the pooled cohort equations have long been viewed as problematic. 

“Because these equations were based on cohorts from the 1960s and 70s, it is believed they overestimate the current population’s risk of MI and stroke as the burden of disease has shifted in the intervening 50-60 years,” he said.

 

Current Equations Overestimate Risk

The new equations are based on more recent, representative, and diverse cohorts that capture a wider spectrum of the population in terms of race, ethnicity, and socioeconomic status. They also include factors that are now known to be relevant to cardiovascular risk, such as chronic kidney disease.

Anderson compared how the two sets of equations estimated risk of cardiovascular disease in the next 10 years in the US population using the NHANES survey — a large nationally representative survey conducted between 2017 and 2020. 

He found that the pooled cohort equations estimated the population average 10-year risk of cardiovascular disease to be about 8%, but the PREVENT equations estimated it at just over 4%.

“The new equations estimate that the middle-aged US population have almost half the level of risk of MI and stroke over next 10 years compared with the equations used currently. So, we will substantially change risk estimates if the new equations are introduced into practice,” Anderson said. 

The study found that, if the PREVENT equations are adopted in the next set of primary prevention guidelines and the current threshold of a 7.5% risk of having an MI or stroke in the next 10 years is maintained as the starting point for statin treatment, then 17.3 million adults who were previously recommended primary prevention statin therapy would no longer be eligible.

A second, similar study, conducted by a different team of US researchers, estimated that using PREVENT would decrease the number of US adults receiving or recommended for statin therapy by 14.3 million and antihypertensive therapy by 2.62 million.

The researchers, led by James A. Diao, MD, from Harvard Medical School, Boston, Massachusetts, also suggested that over 10 years, reductions in treatment eligibility could result in an estimated 107,000 additional MI or stroke events.

Anderson points out that using the new equations would not affect the highest-risk patients. “They are still going to be high risk whichever equations are used. If you smoke a pack of cigarettes a day, have very high blood pressure or cholesterol and are older, then you are high risk. That part hasn’t changed. These people will qualify for statin treatment many times over with both sets of guidelines,” he said. 

Rather it will be the large population at moderate risk of cardiovascular disease that will be affected, with far fewer of these individuals likely to get statins.

“If you are on the fence about whether to take a statin or not and you’re currently just on the threshold where they might be recommended then these new equations could mean that you’ll be less likely to be offered them,” he said. “Using the new equations may result in a delay of a couple of years to have that conversation.”

 

A Red Flag

Steve Nissen, MD, a cardiologist at the Cleveland Clinic in Ohio, is not a fan of cardiovascular risk equations in general. He points out that less than half of those currently eligible for statins are actually treated. And he believes the studies suggesting fewer people will be eligible with the new risk equations raise a red flag on whether they should be used.

“Anything that may result in fewer people being treated is a huge problem,” he told this news organization. “We have abundant evidence that we should be treating more people, not fewer people. Every study we have done has shown benefit with statins.”

The risk calculators were initially developed to limit use of statins and other medications to high-risk patients, he said, but now that we know more about safety of these drugs, it’s clear that the risks are almost nonexistent. 

“We really need something else to guide the prescription of statins,” said Nissen.

Nissen suggests the risk calculators and guidelines have resulted in undertreatment of the population because they lack nuance and put too much emphasis on age. We should be more interested in reducing the lifetime risk of cardiovascular events, he said. “Calculators don’t do a good job of that. Their time horizons are too short. Young people with a family history of cardiovascular disease may have a low 10-year risk on a risk calculator but their lifetime risk is elevated, and as such, they should be considered for statin treatment. We need to find a more nuanced approach to understanding the lifetime risk of individuals,” he said. 

Nissen said risk calculators can be useful in high-risk patients to help demonstrate their need for treatment. “I can show them the calculator and that they have a 20% chance of an event — that can help convince them to take a statin.” 

But at the lower end of the risk scale, “all it does is keep patients who should be getting treatment from having that treatment.”

Nissen said changing the risk calculator won’t affect how he treats patients. “I use judgment to decide who to treat based on scientific literature and the patient in front of me. We will engage in a discussion and make a shared decision on what is the best course of action. Calculators will never be a substitute for medical judgment,” he said.

 

Equations Don’t Decide

Sadiya Khan, MD, a cardiologist at Northwestern University, Evanston, Illinois, and lead author of the PREVENT equations, told this news organization that it is important to put this discussion into context.

“The two recent papers do a good job of describing differences in predictive risk between the two sets of equations but that’s where they stop,” she said. “The translation from that to the decision on who should or should not be on statins or other medications is a step too far.”

Clinical guidelines will need to be updated to take the PREVENT equations into account, as Khan argued in a JAMA editorial. So it is not clear whether the current 7.5% 10-year risk figure will remain the threshold to start treatment. Khan anticipates the guidelines committee will have to re-evaluate that threshold.

“The 7.5% risk threshold was advised in the 2013 guidelines, based on what we knew then about the balance between benefit and harm and with the knowledge that the risk equations overestimated risk,” she said. “We now have a lot more data on the safety of statin therapy. We see this frequently in preventive care. Treatments often becomes more widespread in time and use expands into lower-risk patients.”

She also pointed out that the current primary prevention guidelines encourage consideration of other factors, not just predictive risk scores, when thinking about starting statins, including very high LDL cholesterol, family history, and apo B and Lp(a) levels.

“The recommendation on who would qualify for statin therapy is not based on one number,” she said. “It is based on many considerations, including both qualitative and quantitative factors, and discussions between the patient and the doctor. It is not a straightforward yes or no based on a 7.5% risk threshold.”

The equations, she said, should only be viewed as the first step in the process, and she said she agrees with Nissen that when applying the equations, doctors need to use additional data from each individual patient to make a judgment. “Equations do not decide who gets treated. Clinical practice guidelines do that.” 

Khan also agreed with Nissen that more effort is needed to identify longer term cardiovascular risk in younger people, and so the PREVENT equations include 30-year risk estimates.

“I totally agree that we need to start earlier in having these prevention conversations. The PREVENT model starts at age 30 which is 10 years earlier than the pooled cohort equations and they add a 30-year time horizon as well as the 10-year period for these discussions on predicted risk estimates,” she said. “We need to make sure we are not missing risk in young adults just because we are waiting for them to get into some arbitrary age category.”

Khan says she believes that, used correctly, the new equations will not limit access to statins or other cardiovascular treatments. “Because they are a more accurate reflection of risk in the contemporary population, the new PREVENT equations should identify the correct patients to be treated, within the confines of knowing that no risk prediction equation is perfect,” she said. “And if everything else is considered as well, not just the numbers in the risk equations, it shouldn’t result in fewer patients being treated.”

Anderson reported receiving grants from the American Heart Association, the American College of Cardiology, and the US Deprescribing Research Network. Nissen is leading a development program for a nonprescription low dose of rosuvastatin. He is also involved in trials of a new cholesterol lowering drug, obicetrapib, and on trials on drugs that lower Lp(a). Khan reported receiving grants from the American Heart Association and National Heart, Lung, and Blood Institute.

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

An individual’s estimated risk of having a heart attack or stroke in the next 10 years is widely used to guide preventative medication prescriptions with statins or antihypertensive drugs in those who have not yet had such an event.

To estimate that risk, doctors use equations that include different risk factors, such as age, cholesterol levels, and blood pressure. The current equations, known as the pooled cohort equations, are considered to be outdated as they were developed in 2013 based on population data from the 1960s and 70s. A new set of risk equations — known as the PREVENT equations — were developed by the American Heart Association (AHA) in 2023, and are based on a more contemporary population. It is anticipated that AHA will recommend these new risk equations be used in clinical practice in the next primary prevention guidelines.

But could these new risk equations do more harm than good?

Two recent studies found that applying the PREVENT risk equations to the US population results in a much lower overall level of risk compared with the pooled cohort equations. And, if the current threshold for starting statin treatment — which is an estimated 7.5% risk of having a heart attack or stroke in the next 10 years — is kept the same, this would result in many fewer patients being eligible for statin treatment.

As cardiovascular risk is also used to guide antihypertensive treatment, the new risk equations would also result in fewer people with borderline high blood pressure being eligible for those medications.

This has raised concerns in the medical community, where there is a widespread view that many more people would benefit from primary prevention treatment, and that anything that may cause fewer people to receive these medications would be harmful. 

“I believe the new equations more accurately predict the risk of the current US population, but we need to be aware of what effect that may have on use of statins,” said Tim Anderson, MD, who studies healthcare delivery at the University of Pittsburgh in Pennsylvania and is lead author of one of the studies evaluating the equations.

Anderson told this news organization that the pooled cohort equations have long been viewed as problematic. 

“Because these equations were based on cohorts from the 1960s and 70s, it is believed they overestimate the current population’s risk of MI and stroke as the burden of disease has shifted in the intervening 50-60 years,” he said.

 

Current Equations Overestimate Risk

The new equations are based on more recent, representative, and diverse cohorts that capture a wider spectrum of the population in terms of race, ethnicity, and socioeconomic status. They also include factors that are now known to be relevant to cardiovascular risk, such as chronic kidney disease.

Anderson compared how the two sets of equations estimated risk of cardiovascular disease in the next 10 years in the US population using the NHANES survey — a large nationally representative survey conducted between 2017 and 2020. 

He found that the pooled cohort equations estimated the population average 10-year risk of cardiovascular disease to be about 8%, but the PREVENT equations estimated it at just over 4%.

“The new equations estimate that the middle-aged US population have almost half the level of risk of MI and stroke over next 10 years compared with the equations used currently. So, we will substantially change risk estimates if the new equations are introduced into practice,” Anderson said. 

The study found that, if the PREVENT equations are adopted in the next set of primary prevention guidelines and the current threshold of a 7.5% risk of having an MI or stroke in the next 10 years is maintained as the starting point for statin treatment, then 17.3 million adults who were previously recommended primary prevention statin therapy would no longer be eligible.

A second, similar study, conducted by a different team of US researchers, estimated that using PREVENT would decrease the number of US adults receiving or recommended for statin therapy by 14.3 million and antihypertensive therapy by 2.62 million.

The researchers, led by James A. Diao, MD, from Harvard Medical School, Boston, Massachusetts, also suggested that over 10 years, reductions in treatment eligibility could result in an estimated 107,000 additional MI or stroke events.

Anderson points out that using the new equations would not affect the highest-risk patients. “They are still going to be high risk whichever equations are used. If you smoke a pack of cigarettes a day, have very high blood pressure or cholesterol and are older, then you are high risk. That part hasn’t changed. These people will qualify for statin treatment many times over with both sets of guidelines,” he said. 

Rather it will be the large population at moderate risk of cardiovascular disease that will be affected, with far fewer of these individuals likely to get statins.

“If you are on the fence about whether to take a statin or not and you’re currently just on the threshold where they might be recommended then these new equations could mean that you’ll be less likely to be offered them,” he said. “Using the new equations may result in a delay of a couple of years to have that conversation.”

 

A Red Flag

Steve Nissen, MD, a cardiologist at the Cleveland Clinic in Ohio, is not a fan of cardiovascular risk equations in general. He points out that less than half of those currently eligible for statins are actually treated. And he believes the studies suggesting fewer people will be eligible with the new risk equations raise a red flag on whether they should be used.

“Anything that may result in fewer people being treated is a huge problem,” he told this news organization. “We have abundant evidence that we should be treating more people, not fewer people. Every study we have done has shown benefit with statins.”

The risk calculators were initially developed to limit use of statins and other medications to high-risk patients, he said, but now that we know more about safety of these drugs, it’s clear that the risks are almost nonexistent. 

“We really need something else to guide the prescription of statins,” said Nissen.

Nissen suggests the risk calculators and guidelines have resulted in undertreatment of the population because they lack nuance and put too much emphasis on age. We should be more interested in reducing the lifetime risk of cardiovascular events, he said. “Calculators don’t do a good job of that. Their time horizons are too short. Young people with a family history of cardiovascular disease may have a low 10-year risk on a risk calculator but their lifetime risk is elevated, and as such, they should be considered for statin treatment. We need to find a more nuanced approach to understanding the lifetime risk of individuals,” he said. 

Nissen said risk calculators can be useful in high-risk patients to help demonstrate their need for treatment. “I can show them the calculator and that they have a 20% chance of an event — that can help convince them to take a statin.” 

But at the lower end of the risk scale, “all it does is keep patients who should be getting treatment from having that treatment.”

Nissen said changing the risk calculator won’t affect how he treats patients. “I use judgment to decide who to treat based on scientific literature and the patient in front of me. We will engage in a discussion and make a shared decision on what is the best course of action. Calculators will never be a substitute for medical judgment,” he said.

 

Equations Don’t Decide

Sadiya Khan, MD, a cardiologist at Northwestern University, Evanston, Illinois, and lead author of the PREVENT equations, told this news organization that it is important to put this discussion into context.

“The two recent papers do a good job of describing differences in predictive risk between the two sets of equations but that’s where they stop,” she said. “The translation from that to the decision on who should or should not be on statins or other medications is a step too far.”

Clinical guidelines will need to be updated to take the PREVENT equations into account, as Khan argued in a JAMA editorial. So it is not clear whether the current 7.5% 10-year risk figure will remain the threshold to start treatment. Khan anticipates the guidelines committee will have to re-evaluate that threshold.

“The 7.5% risk threshold was advised in the 2013 guidelines, based on what we knew then about the balance between benefit and harm and with the knowledge that the risk equations overestimated risk,” she said. “We now have a lot more data on the safety of statin therapy. We see this frequently in preventive care. Treatments often becomes more widespread in time and use expands into lower-risk patients.”

She also pointed out that the current primary prevention guidelines encourage consideration of other factors, not just predictive risk scores, when thinking about starting statins, including very high LDL cholesterol, family history, and apo B and Lp(a) levels.

“The recommendation on who would qualify for statin therapy is not based on one number,” she said. “It is based on many considerations, including both qualitative and quantitative factors, and discussions between the patient and the doctor. It is not a straightforward yes or no based on a 7.5% risk threshold.”

The equations, she said, should only be viewed as the first step in the process, and she said she agrees with Nissen that when applying the equations, doctors need to use additional data from each individual patient to make a judgment. “Equations do not decide who gets treated. Clinical practice guidelines do that.” 

Khan also agreed with Nissen that more effort is needed to identify longer term cardiovascular risk in younger people, and so the PREVENT equations include 30-year risk estimates.

“I totally agree that we need to start earlier in having these prevention conversations. The PREVENT model starts at age 30 which is 10 years earlier than the pooled cohort equations and they add a 30-year time horizon as well as the 10-year period for these discussions on predicted risk estimates,” she said. “We need to make sure we are not missing risk in young adults just because we are waiting for them to get into some arbitrary age category.”

Khan says she believes that, used correctly, the new equations will not limit access to statins or other cardiovascular treatments. “Because they are a more accurate reflection of risk in the contemporary population, the new PREVENT equations should identify the correct patients to be treated, within the confines of knowing that no risk prediction equation is perfect,” she said. “And if everything else is considered as well, not just the numbers in the risk equations, it shouldn’t result in fewer patients being treated.”

Anderson reported receiving grants from the American Heart Association, the American College of Cardiology, and the US Deprescribing Research Network. Nissen is leading a development program for a nonprescription low dose of rosuvastatin. He is also involved in trials of a new cholesterol lowering drug, obicetrapib, and on trials on drugs that lower Lp(a). Khan reported receiving grants from the American Heart Association and National Heart, Lung, and Blood Institute.

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

An individual’s estimated risk of having a heart attack or stroke in the next 10 years is widely used to guide preventative medication prescriptions with statins or antihypertensive drugs in those who have not yet had such an event.

To estimate that risk, doctors use equations that include different risk factors, such as age, cholesterol levels, and blood pressure. The current equations, known as the pooled cohort equations, are considered to be outdated as they were developed in 2013 based on population data from the 1960s and 70s. A new set of risk equations — known as the PREVENT equations — were developed by the American Heart Association (AHA) in 2023, and are based on a more contemporary population. It is anticipated that AHA will recommend these new risk equations be used in clinical practice in the next primary prevention guidelines.

But could these new risk equations do more harm than good?

Two recent studies found that applying the PREVENT risk equations to the US population results in a much lower overall level of risk compared with the pooled cohort equations. And, if the current threshold for starting statin treatment — which is an estimated 7.5% risk of having a heart attack or stroke in the next 10 years — is kept the same, this would result in many fewer patients being eligible for statin treatment.

As cardiovascular risk is also used to guide antihypertensive treatment, the new risk equations would also result in fewer people with borderline high blood pressure being eligible for those medications.

This has raised concerns in the medical community, where there is a widespread view that many more people would benefit from primary prevention treatment, and that anything that may cause fewer people to receive these medications would be harmful. 

“I believe the new equations more accurately predict the risk of the current US population, but we need to be aware of what effect that may have on use of statins,” said Tim Anderson, MD, who studies healthcare delivery at the University of Pittsburgh in Pennsylvania and is lead author of one of the studies evaluating the equations.

Anderson told this news organization that the pooled cohort equations have long been viewed as problematic. 

“Because these equations were based on cohorts from the 1960s and 70s, it is believed they overestimate the current population’s risk of MI and stroke as the burden of disease has shifted in the intervening 50-60 years,” he said.

 

Current Equations Overestimate Risk

The new equations are based on more recent, representative, and diverse cohorts that capture a wider spectrum of the population in terms of race, ethnicity, and socioeconomic status. They also include factors that are now known to be relevant to cardiovascular risk, such as chronic kidney disease.

Anderson compared how the two sets of equations estimated risk of cardiovascular disease in the next 10 years in the US population using the NHANES survey — a large nationally representative survey conducted between 2017 and 2020. 

He found that the pooled cohort equations estimated the population average 10-year risk of cardiovascular disease to be about 8%, but the PREVENT equations estimated it at just over 4%.

“The new equations estimate that the middle-aged US population have almost half the level of risk of MI and stroke over next 10 years compared with the equations used currently. So, we will substantially change risk estimates if the new equations are introduced into practice,” Anderson said. 

The study found that, if the PREVENT equations are adopted in the next set of primary prevention guidelines and the current threshold of a 7.5% risk of having an MI or stroke in the next 10 years is maintained as the starting point for statin treatment, then 17.3 million adults who were previously recommended primary prevention statin therapy would no longer be eligible.

A second, similar study, conducted by a different team of US researchers, estimated that using PREVENT would decrease the number of US adults receiving or recommended for statin therapy by 14.3 million and antihypertensive therapy by 2.62 million.

The researchers, led by James A. Diao, MD, from Harvard Medical School, Boston, Massachusetts, also suggested that over 10 years, reductions in treatment eligibility could result in an estimated 107,000 additional MI or stroke events.

Anderson points out that using the new equations would not affect the highest-risk patients. “They are still going to be high risk whichever equations are used. If you smoke a pack of cigarettes a day, have very high blood pressure or cholesterol and are older, then you are high risk. That part hasn’t changed. These people will qualify for statin treatment many times over with both sets of guidelines,” he said. 

Rather it will be the large population at moderate risk of cardiovascular disease that will be affected, with far fewer of these individuals likely to get statins.

“If you are on the fence about whether to take a statin or not and you’re currently just on the threshold where they might be recommended then these new equations could mean that you’ll be less likely to be offered them,” he said. “Using the new equations may result in a delay of a couple of years to have that conversation.”

 

A Red Flag

Steve Nissen, MD, a cardiologist at the Cleveland Clinic in Ohio, is not a fan of cardiovascular risk equations in general. He points out that less than half of those currently eligible for statins are actually treated. And he believes the studies suggesting fewer people will be eligible with the new risk equations raise a red flag on whether they should be used.

“Anything that may result in fewer people being treated is a huge problem,” he told this news organization. “We have abundant evidence that we should be treating more people, not fewer people. Every study we have done has shown benefit with statins.”

The risk calculators were initially developed to limit use of statins and other medications to high-risk patients, he said, but now that we know more about safety of these drugs, it’s clear that the risks are almost nonexistent. 

“We really need something else to guide the prescription of statins,” said Nissen.

Nissen suggests the risk calculators and guidelines have resulted in undertreatment of the population because they lack nuance and put too much emphasis on age. We should be more interested in reducing the lifetime risk of cardiovascular events, he said. “Calculators don’t do a good job of that. Their time horizons are too short. Young people with a family history of cardiovascular disease may have a low 10-year risk on a risk calculator but their lifetime risk is elevated, and as such, they should be considered for statin treatment. We need to find a more nuanced approach to understanding the lifetime risk of individuals,” he said. 

Nissen said risk calculators can be useful in high-risk patients to help demonstrate their need for treatment. “I can show them the calculator and that they have a 20% chance of an event — that can help convince them to take a statin.” 

But at the lower end of the risk scale, “all it does is keep patients who should be getting treatment from having that treatment.”

Nissen said changing the risk calculator won’t affect how he treats patients. “I use judgment to decide who to treat based on scientific literature and the patient in front of me. We will engage in a discussion and make a shared decision on what is the best course of action. Calculators will never be a substitute for medical judgment,” he said.

 

Equations Don’t Decide

Sadiya Khan, MD, a cardiologist at Northwestern University, Evanston, Illinois, and lead author of the PREVENT equations, told this news organization that it is important to put this discussion into context.

“The two recent papers do a good job of describing differences in predictive risk between the two sets of equations but that’s where they stop,” she said. “The translation from that to the decision on who should or should not be on statins or other medications is a step too far.”

Clinical guidelines will need to be updated to take the PREVENT equations into account, as Khan argued in a JAMA editorial. So it is not clear whether the current 7.5% 10-year risk figure will remain the threshold to start treatment. Khan anticipates the guidelines committee will have to re-evaluate that threshold.

“The 7.5% risk threshold was advised in the 2013 guidelines, based on what we knew then about the balance between benefit and harm and with the knowledge that the risk equations overestimated risk,” she said. “We now have a lot more data on the safety of statin therapy. We see this frequently in preventive care. Treatments often becomes more widespread in time and use expands into lower-risk patients.”

She also pointed out that the current primary prevention guidelines encourage consideration of other factors, not just predictive risk scores, when thinking about starting statins, including very high LDL cholesterol, family history, and apo B and Lp(a) levels.

“The recommendation on who would qualify for statin therapy is not based on one number,” she said. “It is based on many considerations, including both qualitative and quantitative factors, and discussions between the patient and the doctor. It is not a straightforward yes or no based on a 7.5% risk threshold.”

The equations, she said, should only be viewed as the first step in the process, and she said she agrees with Nissen that when applying the equations, doctors need to use additional data from each individual patient to make a judgment. “Equations do not decide who gets treated. Clinical practice guidelines do that.” 

Khan also agreed with Nissen that more effort is needed to identify longer term cardiovascular risk in younger people, and so the PREVENT equations include 30-year risk estimates.

“I totally agree that we need to start earlier in having these prevention conversations. The PREVENT model starts at age 30 which is 10 years earlier than the pooled cohort equations and they add a 30-year time horizon as well as the 10-year period for these discussions on predicted risk estimates,” she said. “We need to make sure we are not missing risk in young adults just because we are waiting for them to get into some arbitrary age category.”

Khan says she believes that, used correctly, the new equations will not limit access to statins or other cardiovascular treatments. “Because they are a more accurate reflection of risk in the contemporary population, the new PREVENT equations should identify the correct patients to be treated, within the confines of knowing that no risk prediction equation is perfect,” she said. “And if everything else is considered as well, not just the numbers in the risk equations, it shouldn’t result in fewer patients being treated.”

Anderson reported receiving grants from the American Heart Association, the American College of Cardiology, and the US Deprescribing Research Network. Nissen is leading a development program for a nonprescription low dose of rosuvastatin. He is also involved in trials of a new cholesterol lowering drug, obicetrapib, and on trials on drugs that lower Lp(a). Khan reported receiving grants from the American Heart Association and National Heart, Lung, and Blood Institute.

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