Clinical Endocrinology News

Florida’s two main medical bodies have voted to stop gender-affirming treatment of children, including the use of puberty blockers, cross-sex hormones, and surgery, other than in minors who are already receiving such care.

The move, which is unprecedented, makes Florida one of several U.S. states to restrict gender-affirming care for adolescents, but the first to do so via an administrative process, through the actions of its Board of Medicine and Board of Osteopathic Medicine.

“I appreciate the integrity of the Boards for ruling in the best interest of children in Florida despite facing tremendous pressure to permit these unproven and risky treatments,” Florida Surgeon General Joseph Ladapo, MD, PhD, said in a statement.

In a statement, The Endocrine Society criticizes the decision as “blatantly discriminatory” and not based on medical evidence.

During a meeting on Oct. 28 that involved testimonies from doctors, parents of transgender children, detransitioners, and patients, board members referred to similar changes in Europe, where some countries have pushed psychotherapy instead of surgery or hormone treatment.

Then, on Nov. 4, the boards each set slightly different instructions, with the Board of Osteopathic Medicine voting to restrict care for new patients but allowing an exception for children enrolled in clinical studies, which “must include long-term longitudinal assessments of the patients’ physiologic and psychologic outcomes,” according to the Florida Department of Health.

The Board of Medicine did not allow the latter.

The proposed rules are open to public comment before finalization.

Arkansas was the first state to enact such a ban on gender-affirming care, with Republican lawmakers in 2021 overriding GOP Gov. Asa Hutchinson’s veto of the legislation. Alabama Republicans in 2022 approved legislation to outlaw gender-affirming medications for transgender youths. Both laws have been paused amid unfolding legal battles, according to Associated Press.

Oklahoma Gov. Kevin Stitt, a Republican, signed a bill in October that bars federal funds earmarked for the University of Oklahoma Medical Center from being used for gender reassignment treatments for minors. Gov. Stitt also called for the legislature to ban some of those gender reassignment treatments statewide when it returns in February.

Top Tennessee Republicans also have vowed to push for strict antitransgender policies. The state already bans doctors from providing gender-confirming hormone treatment to prepubescent minors. To date, no one has legally challenged the law as medical experts maintain no doctor in Tennessee does so.

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

Florida’s two main medical bodies have voted to stop gender-affirming treatment of children, including the use of puberty blockers, cross-sex hormones, and surgery, other than in minors who are already receiving such care.

The move, which is unprecedented, makes Florida one of several U.S. states to restrict gender-affirming care for adolescents, but the first to do so via an administrative process, through the actions of its Board of Medicine and Board of Osteopathic Medicine.

“I appreciate the integrity of the Boards for ruling in the best interest of children in Florida despite facing tremendous pressure to permit these unproven and risky treatments,” Florida Surgeon General Joseph Ladapo, MD, PhD, said in a statement.

In a statement, The Endocrine Society criticizes the decision as “blatantly discriminatory” and not based on medical evidence.

During a meeting on Oct. 28 that involved testimonies from doctors, parents of transgender children, detransitioners, and patients, board members referred to similar changes in Europe, where some countries have pushed psychotherapy instead of surgery or hormone treatment.

Then, on Nov. 4, the boards each set slightly different instructions, with the Board of Osteopathic Medicine voting to restrict care for new patients but allowing an exception for children enrolled in clinical studies, which “must include long-term longitudinal assessments of the patients’ physiologic and psychologic outcomes,” according to the Florida Department of Health.

The Board of Medicine did not allow the latter.

The proposed rules are open to public comment before finalization.

Arkansas was the first state to enact such a ban on gender-affirming care, with Republican lawmakers in 2021 overriding GOP Gov. Asa Hutchinson’s veto of the legislation. Alabama Republicans in 2022 approved legislation to outlaw gender-affirming medications for transgender youths. Both laws have been paused amid unfolding legal battles, according to Associated Press.

Oklahoma Gov. Kevin Stitt, a Republican, signed a bill in October that bars federal funds earmarked for the University of Oklahoma Medical Center from being used for gender reassignment treatments for minors. Gov. Stitt also called for the legislature to ban some of those gender reassignment treatments statewide when it returns in February.

Top Tennessee Republicans also have vowed to push for strict antitransgender policies. The state already bans doctors from providing gender-confirming hormone treatment to prepubescent minors. To date, no one has legally challenged the law as medical experts maintain no doctor in Tennessee does so.

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

Florida’s two main medical bodies have voted to stop gender-affirming treatment of children, including the use of puberty blockers, cross-sex hormones, and surgery, other than in minors who are already receiving such care.

The move, which is unprecedented, makes Florida one of several U.S. states to restrict gender-affirming care for adolescents, but the first to do so via an administrative process, through the actions of its Board of Medicine and Board of Osteopathic Medicine.

“I appreciate the integrity of the Boards for ruling in the best interest of children in Florida despite facing tremendous pressure to permit these unproven and risky treatments,” Florida Surgeon General Joseph Ladapo, MD, PhD, said in a statement.

In a statement, The Endocrine Society criticizes the decision as “blatantly discriminatory” and not based on medical evidence.

During a meeting on Oct. 28 that involved testimonies from doctors, parents of transgender children, detransitioners, and patients, board members referred to similar changes in Europe, where some countries have pushed psychotherapy instead of surgery or hormone treatment.

Then, on Nov. 4, the boards each set slightly different instructions, with the Board of Osteopathic Medicine voting to restrict care for new patients but allowing an exception for children enrolled in clinical studies, which “must include long-term longitudinal assessments of the patients’ physiologic and psychologic outcomes,” according to the Florida Department of Health.

The Board of Medicine did not allow the latter.

The proposed rules are open to public comment before finalization.

Arkansas was the first state to enact such a ban on gender-affirming care, with Republican lawmakers in 2021 overriding GOP Gov. Asa Hutchinson’s veto of the legislation. Alabama Republicans in 2022 approved legislation to outlaw gender-affirming medications for transgender youths. Both laws have been paused amid unfolding legal battles, according to Associated Press.

Oklahoma Gov. Kevin Stitt, a Republican, signed a bill in October that bars federal funds earmarked for the University of Oklahoma Medical Center from being used for gender reassignment treatments for minors. Gov. Stitt also called for the legislature to ban some of those gender reassignment treatments statewide when it returns in February.

Top Tennessee Republicans also have vowed to push for strict antitransgender policies. The state already bans doctors from providing gender-confirming hormone treatment to prepubescent minors. To date, no one has legally challenged the law as medical experts maintain no doctor in Tennessee does so.

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

Who watches the ED staff?

We heard a really great joke recently, one we simply have to share.

A man in Seattle went to a therapist. “I’m depressed,” he says. “Depressed, overworked, and lonely.”

Chinnapong/iStock/Getty Images

“Oh dear, that sounds quite serious,” the therapist replies. “Tell me all about it.”

“Life just seems so harsh and cruel,” the man explains. “The pandemic has caused 300,000 health care workers across the country to leave the industry.”

“Such as the doctor typically filling this role in the joke,” the therapist, who is not licensed to prescribe medicine, nods.

“Exactly! And with so many respiratory viruses circulating and COVID still hanging around, emergency departments all over the country are facing massive backups. People are waiting outside the hospital for hours, hoping a bed will open up. Things got so bad at a hospital near Seattle in October that a nurse called 911 on her own ED. Told the 911 operator to send the fire department to help out, since they were ‘drowning’ and ‘in dire straits.’ They had 45 patients waiting and only five nurses to take care of them.”

“That is quite serious,” the therapist says, scribbling down unseen notes.

“The fire chief did send a crew out, and they cleaned rooms, changed beds, and took vitals for 90 minutes until the crisis passed,” the man says. “But it’s only a matter of time before it happens again. The hospital president said they have 300 open positions, and literally no one has applied to work in the emergency department. Not one person.”

“And how does all this make you feel?” the therapist asks.

“I feel all alone,” the man says. “This world feels so threatening, like no one cares, and I have no idea what will come next. It’s so vague and uncertain.”

“Ah, I think I have a solution for you,” the therapist says. “Go to the emergency department at St. Michael Medical Center in Silverdale, near Seattle. They’ll get your bad mood all settled, and they’ll prescribe you the medicine you need to relax.”

The man bursts into tears. “You don’t understand,” he says. “I am the emergency department at St. Michael Medical Center.”

Good joke. Everybody laugh. Roll on snare drum. Curtains.

Myth buster: Supplements for cholesterol lowering

When it comes to that nasty low-density lipoprotein cholesterol, some people swear by supplements over statins as a holistic approach. Well, we’re busting the myth that those heart-healthy supplements are even effective in comparison.

Sally Kubetin/MDedge News

Which supplements are we talking about? These six are always on sale at the pharmacy: fish oil, cinnamon, garlic, turmeric, plant sterols, and red yeast rice.

In a study presented at the recent American Heart Association scientific sessions, researchers compared these supplements’ effectiveness in lowering LDL cholesterol with low-dose rosuvastatin or placebo among 199 adults aged 40-75 years who didn’t have a personal history of cardiovascular disease.

Participants who took the statin for 28 days had an average of 24% decrease in total cholesterol and a 38% reduction in LDL cholesterol, while 28 days’ worth of the supplements did no better than the placebo in either measure. Compared with placebo, the plant sterols supplement notably lowered HDL cholesterol and the garlic supplement notably increased LDL cholesterol.

Even though there are other studies showing the validity of plant sterols and red yeast rice to lower LDL cholesterol, author Luke J. Laffin, MD, of the Cleveland Clinic noted that this study shows how supplement results can vary and that more research is needed to see the effect they truly have on cholesterol over time.

So, should you stop taking or recommending supplements for heart health or healthy cholesterol levels? Well, we’re not going to come to your house and raid your medicine cabinet, but the authors of this study are definitely not saying that you should rely on them.

Consider this myth mostly busted.
 

COVID dept. of unintended consequences, part 2

The surveillance testing programs conducted in the first year of the pandemic were, in theory, meant to keep everyone safer. Someone, apparently, forgot to explain that to the students of the University of Wyoming and the University of Idaho.

Luis Alvarez/Getty Images

We’re all familiar with the drill: Students at the two schools had to undergo frequent COVID screening to keep the virus from spreading, thereby making everyone safer. Duck your head now, because here comes the unintended consequence.

The students who didn’t get COVID eventually, and perhaps not so surprisingly, “perceived that the mandatory testing policy decreased their risk of contracting COVID-19, and … this perception led to higher participation in COVID-risky events,” Chian Jones Ritten, PhD, and associates said in PNAS Nexus.

They surveyed 757 students from the Univ. of Washington and 517 from the Univ. of Idaho and found that those who were tested more frequently perceived that they were less likely to contract the virus. Those respondents also more frequently attended indoor gatherings, both small and large, and spent more time in restaurants and bars.

The investigators did not mince words: “From a public health standpoint, such behavior is problematic.”

Current parents/participants in the workforce might have other ideas about an appropriate response to COVID.

At this point, we probably should mention that appropriation is the second-most sincere form of flattery.

Who watches the ED staff?

We heard a really great joke recently, one we simply have to share.

A man in Seattle went to a therapist. “I’m depressed,” he says. “Depressed, overworked, and lonely.”

Chinnapong/iStock/Getty Images

“Oh dear, that sounds quite serious,” the therapist replies. “Tell me all about it.”

“Life just seems so harsh and cruel,” the man explains. “The pandemic has caused 300,000 health care workers across the country to leave the industry.”

“Such as the doctor typically filling this role in the joke,” the therapist, who is not licensed to prescribe medicine, nods.

“Exactly! And with so many respiratory viruses circulating and COVID still hanging around, emergency departments all over the country are facing massive backups. People are waiting outside the hospital for hours, hoping a bed will open up. Things got so bad at a hospital near Seattle in October that a nurse called 911 on her own ED. Told the 911 operator to send the fire department to help out, since they were ‘drowning’ and ‘in dire straits.’ They had 45 patients waiting and only five nurses to take care of them.”

“That is quite serious,” the therapist says, scribbling down unseen notes.

“The fire chief did send a crew out, and they cleaned rooms, changed beds, and took vitals for 90 minutes until the crisis passed,” the man says. “But it’s only a matter of time before it happens again. The hospital president said they have 300 open positions, and literally no one has applied to work in the emergency department. Not one person.”

“And how does all this make you feel?” the therapist asks.

“I feel all alone,” the man says. “This world feels so threatening, like no one cares, and I have no idea what will come next. It’s so vague and uncertain.”

“Ah, I think I have a solution for you,” the therapist says. “Go to the emergency department at St. Michael Medical Center in Silverdale, near Seattle. They’ll get your bad mood all settled, and they’ll prescribe you the medicine you need to relax.”

The man bursts into tears. “You don’t understand,” he says. “I am the emergency department at St. Michael Medical Center.”

Good joke. Everybody laugh. Roll on snare drum. Curtains.

Myth buster: Supplements for cholesterol lowering

When it comes to that nasty low-density lipoprotein cholesterol, some people swear by supplements over statins as a holistic approach. Well, we’re busting the myth that those heart-healthy supplements are even effective in comparison.

Sally Kubetin/MDedge News

Which supplements are we talking about? These six are always on sale at the pharmacy: fish oil, cinnamon, garlic, turmeric, plant sterols, and red yeast rice.

In a study presented at the recent American Heart Association scientific sessions, researchers compared these supplements’ effectiveness in lowering LDL cholesterol with low-dose rosuvastatin or placebo among 199 adults aged 40-75 years who didn’t have a personal history of cardiovascular disease.

Participants who took the statin for 28 days had an average of 24% decrease in total cholesterol and a 38% reduction in LDL cholesterol, while 28 days’ worth of the supplements did no better than the placebo in either measure. Compared with placebo, the plant sterols supplement notably lowered HDL cholesterol and the garlic supplement notably increased LDL cholesterol.

Even though there are other studies showing the validity of plant sterols and red yeast rice to lower LDL cholesterol, author Luke J. Laffin, MD, of the Cleveland Clinic noted that this study shows how supplement results can vary and that more research is needed to see the effect they truly have on cholesterol over time.

So, should you stop taking or recommending supplements for heart health or healthy cholesterol levels? Well, we’re not going to come to your house and raid your medicine cabinet, but the authors of this study are definitely not saying that you should rely on them.

Consider this myth mostly busted.
 

COVID dept. of unintended consequences, part 2

The surveillance testing programs conducted in the first year of the pandemic were, in theory, meant to keep everyone safer. Someone, apparently, forgot to explain that to the students of the University of Wyoming and the University of Idaho.

Luis Alvarez/Getty Images

We’re all familiar with the drill: Students at the two schools had to undergo frequent COVID screening to keep the virus from spreading, thereby making everyone safer. Duck your head now, because here comes the unintended consequence.

The students who didn’t get COVID eventually, and perhaps not so surprisingly, “perceived that the mandatory testing policy decreased their risk of contracting COVID-19, and … this perception led to higher participation in COVID-risky events,” Chian Jones Ritten, PhD, and associates said in PNAS Nexus.

They surveyed 757 students from the Univ. of Washington and 517 from the Univ. of Idaho and found that those who were tested more frequently perceived that they were less likely to contract the virus. Those respondents also more frequently attended indoor gatherings, both small and large, and spent more time in restaurants and bars.

The investigators did not mince words: “From a public health standpoint, such behavior is problematic.”

Current parents/participants in the workforce might have other ideas about an appropriate response to COVID.

At this point, we probably should mention that appropriation is the second-most sincere form of flattery.

Who watches the ED staff?

We heard a really great joke recently, one we simply have to share.

A man in Seattle went to a therapist. “I’m depressed,” he says. “Depressed, overworked, and lonely.”

Chinnapong/iStock/Getty Images

“Oh dear, that sounds quite serious,” the therapist replies. “Tell me all about it.”

“Life just seems so harsh and cruel,” the man explains. “The pandemic has caused 300,000 health care workers across the country to leave the industry.”

“Such as the doctor typically filling this role in the joke,” the therapist, who is not licensed to prescribe medicine, nods.

“Exactly! And with so many respiratory viruses circulating and COVID still hanging around, emergency departments all over the country are facing massive backups. People are waiting outside the hospital for hours, hoping a bed will open up. Things got so bad at a hospital near Seattle in October that a nurse called 911 on her own ED. Told the 911 operator to send the fire department to help out, since they were ‘drowning’ and ‘in dire straits.’ They had 45 patients waiting and only five nurses to take care of them.”

“That is quite serious,” the therapist says, scribbling down unseen notes.

“The fire chief did send a crew out, and they cleaned rooms, changed beds, and took vitals for 90 minutes until the crisis passed,” the man says. “But it’s only a matter of time before it happens again. The hospital president said they have 300 open positions, and literally no one has applied to work in the emergency department. Not one person.”

“And how does all this make you feel?” the therapist asks.

“I feel all alone,” the man says. “This world feels so threatening, like no one cares, and I have no idea what will come next. It’s so vague and uncertain.”

“Ah, I think I have a solution for you,” the therapist says. “Go to the emergency department at St. Michael Medical Center in Silverdale, near Seattle. They’ll get your bad mood all settled, and they’ll prescribe you the medicine you need to relax.”

The man bursts into tears. “You don’t understand,” he says. “I am the emergency department at St. Michael Medical Center.”

Good joke. Everybody laugh. Roll on snare drum. Curtains.

Myth buster: Supplements for cholesterol lowering

When it comes to that nasty low-density lipoprotein cholesterol, some people swear by supplements over statins as a holistic approach. Well, we’re busting the myth that those heart-healthy supplements are even effective in comparison.

Sally Kubetin/MDedge News

Which supplements are we talking about? These six are always on sale at the pharmacy: fish oil, cinnamon, garlic, turmeric, plant sterols, and red yeast rice.

In a study presented at the recent American Heart Association scientific sessions, researchers compared these supplements’ effectiveness in lowering LDL cholesterol with low-dose rosuvastatin or placebo among 199 adults aged 40-75 years who didn’t have a personal history of cardiovascular disease.

Participants who took the statin for 28 days had an average of 24% decrease in total cholesterol and a 38% reduction in LDL cholesterol, while 28 days’ worth of the supplements did no better than the placebo in either measure. Compared with placebo, the plant sterols supplement notably lowered HDL cholesterol and the garlic supplement notably increased LDL cholesterol.

Even though there are other studies showing the validity of plant sterols and red yeast rice to lower LDL cholesterol, author Luke J. Laffin, MD, of the Cleveland Clinic noted that this study shows how supplement results can vary and that more research is needed to see the effect they truly have on cholesterol over time.

So, should you stop taking or recommending supplements for heart health or healthy cholesterol levels? Well, we’re not going to come to your house and raid your medicine cabinet, but the authors of this study are definitely not saying that you should rely on them.

Consider this myth mostly busted.
 

COVID dept. of unintended consequences, part 2

The surveillance testing programs conducted in the first year of the pandemic were, in theory, meant to keep everyone safer. Someone, apparently, forgot to explain that to the students of the University of Wyoming and the University of Idaho.

Luis Alvarez/Getty Images

We’re all familiar with the drill: Students at the two schools had to undergo frequent COVID screening to keep the virus from spreading, thereby making everyone safer. Duck your head now, because here comes the unintended consequence.

The students who didn’t get COVID eventually, and perhaps not so surprisingly, “perceived that the mandatory testing policy decreased their risk of contracting COVID-19, and … this perception led to higher participation in COVID-risky events,” Chian Jones Ritten, PhD, and associates said in PNAS Nexus.

They surveyed 757 students from the Univ. of Washington and 517 from the Univ. of Idaho and found that those who were tested more frequently perceived that they were less likely to contract the virus. Those respondents also more frequently attended indoor gatherings, both small and large, and spent more time in restaurants and bars.

The investigators did not mince words: “From a public health standpoint, such behavior is problematic.”

Current parents/participants in the workforce might have other ideas about an appropriate response to COVID.

At this point, we probably should mention that appropriation is the second-most sincere form of flattery.

People with subclinical hyperthyroidism are at 34% greater risk of experiencing a fracture compared with those with normal thyroid function, new research shows.

The finding, from a study of nearly 11,000 middle-aged men and women followed for a median of 2 decades, “highlights a potential role for more aggressive screening and monitoring of patients with subclinical hyperthyroidism to prevent bone mineral disease,” the researchers wrote.

Primary care physicians “should be more aware of the risks for fracture among persons with subclinical hyperthyroidism in the ambulatory setting,” Natalie R. Daya, a PhD student in epidemiology at Johns Hopkins Bloomberg School of Public Health, Baltimore, and first author of the study, told this news organization.

Ms. Daya and her colleagues published their findings in JAMA Network Open.

 

Building on earlier findings

The results agree with previous work, including a meta-analysis of 13 prospective cohort studies of 70,289 primarily White individuals with an average age of 64 years, which found that subclinical hyperthyroidism was associated with a modestly increased risk for fractures, the researchers noted.

“Our study extends these findings to a younger, community-based cohort that included both Black and White participants, included extensive adjustment for potential confounders, and had a longer follow-up period (median follow-up of 21 years vs. 12 years),” they wrote.

The study included 10,946 participants in the Atherosclerosis Risk in Communities Study who were recruited in Washington County, Maryland; Forsyth County, North Carolina; Jackson, Mississippi; and the suburbs of Minneapolis.

Baseline thyroid function was measured in blood samples collected during the second visit, which occurred between 1990 and 1992. No participants in the new analysis took thyroid medications or had a history of hospitalization for fractures at baseline, and all identified as Black or White. The mean age was 57 years, 24% were Black, and 54.3% were female.

Subclinical hyperthyroidism was defined as a thyrotropin level less than 0.56 mIU/L; subclinical hypothyroidism as a thyrotropin level greater than 5.1 mIU/L; and normal thyroid function as a thyrotropin level between 0.56 and 5.1 mIU/L, with normal free thyroxine levels of 0.85-1.4 ng/dL.

The vast majority (93%) of participants had normal thyroid function, 2.6% had subclinical hyperthyroidism, and 4.4% had subclinical hypothyroidism, according to the researchers.

Median follow-up was 21 years. The researchers identified 3,556 incident fractures, detected with hospitalization discharge codes through 2019 and inpatient and Medicare claims data through 2018, for a rate of 167.1 per 10,000 person-years.

Adjusted hazard ratios for fracture were 1.34 (95% confidence interval [CI], 1.09-1.65) for people with subclinical hyperthyroidism and 0.90 (95% CI, 0.77-1.05) for those with subclinical hypothyroidism, compared with those with normal thyroid function.

Most fractures occurred in either the hip (14.1%) or spine (13.8%), according to the researchers.

Limitations included a lack of thyroid function data during the follow-up period and lack of data on bone mineral density, the researchers wrote.
 

‘An important risk factor’

Endocrinologist Michael McClung, MD, founding and emeritus director of the Oregon Osteoporosis Center, Portland, who was not involved in the study, pointed out that both subclinical hypothyroidism and subclinical hyperthyroidism have been linked to greater risk for cardiovascular disease as well as fracture.

The new paper underscores that subclinical hyperthyroidism “should be included as an important risk factor” for fracture as well as cardiovascular risk, Dr. McClung said in an interview. In considering whether to treat osteoporosis, subclinical hyperthyroidism “may be enough to tip the balance in favor of pharmacological therapy,” he added.

Thyroid-stimulating hormone (TSH) tests to assess thyroid function are typically ordered only if a patient has symptoms of hyperthyroidism or hypothyroidism, Ms. Daya said. Depending on the cause and severity of a low TSH level, a physician may prescribe methimazole or radioactive iodine therapy to reduce the production of thyroxine, she said.

However, well-designed studies are needed to evaluate whether treatment of subclinical thyroid dysfunction reduces the risk for fracture or cardiovascular problems and assess downsides such as side effects, costs, and psychological harm, Dr. McClung noted.

The U.S. Preventive Services Task Force concluded in 2015 that the data were insufficient to recommend screening for thyroid dysfunction in adults without symptoms. As of a year ago, no new evidence has emerged to support an update, according to the task force’s website.

“Until those studies are available, selective screening of thyroid function should be considered in all patients undergoing risk assessment for cardiovascular disease or skeletal health,” Dr. McClung said.

The Atherosclerosis Risk in Communities Study has been funded by the National Heart, Lung, and Blood Institute of the National Institutes of Health (NIH) and the U.S. Department of Health and Human Services. Ms. Daya and four study authors reported receiving NIH grants during the study period. Dr. McClung reported no relevant financial conflicts of interest.

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

People with subclinical hyperthyroidism are at 34% greater risk of experiencing a fracture compared with those with normal thyroid function, new research shows.

The finding, from a study of nearly 11,000 middle-aged men and women followed for a median of 2 decades, “highlights a potential role for more aggressive screening and monitoring of patients with subclinical hyperthyroidism to prevent bone mineral disease,” the researchers wrote.

Primary care physicians “should be more aware of the risks for fracture among persons with subclinical hyperthyroidism in the ambulatory setting,” Natalie R. Daya, a PhD student in epidemiology at Johns Hopkins Bloomberg School of Public Health, Baltimore, and first author of the study, told this news organization.

Ms. Daya and her colleagues published their findings in JAMA Network Open.

 

Building on earlier findings

The results agree with previous work, including a meta-analysis of 13 prospective cohort studies of 70,289 primarily White individuals with an average age of 64 years, which found that subclinical hyperthyroidism was associated with a modestly increased risk for fractures, the researchers noted.

“Our study extends these findings to a younger, community-based cohort that included both Black and White participants, included extensive adjustment for potential confounders, and had a longer follow-up period (median follow-up of 21 years vs. 12 years),” they wrote.

The study included 10,946 participants in the Atherosclerosis Risk in Communities Study who were recruited in Washington County, Maryland; Forsyth County, North Carolina; Jackson, Mississippi; and the suburbs of Minneapolis.

Baseline thyroid function was measured in blood samples collected during the second visit, which occurred between 1990 and 1992. No participants in the new analysis took thyroid medications or had a history of hospitalization for fractures at baseline, and all identified as Black or White. The mean age was 57 years, 24% were Black, and 54.3% were female.

Subclinical hyperthyroidism was defined as a thyrotropin level less than 0.56 mIU/L; subclinical hypothyroidism as a thyrotropin level greater than 5.1 mIU/L; and normal thyroid function as a thyrotropin level between 0.56 and 5.1 mIU/L, with normal free thyroxine levels of 0.85-1.4 ng/dL.

The vast majority (93%) of participants had normal thyroid function, 2.6% had subclinical hyperthyroidism, and 4.4% had subclinical hypothyroidism, according to the researchers.

Median follow-up was 21 years. The researchers identified 3,556 incident fractures, detected with hospitalization discharge codes through 2019 and inpatient and Medicare claims data through 2018, for a rate of 167.1 per 10,000 person-years.

Adjusted hazard ratios for fracture were 1.34 (95% confidence interval [CI], 1.09-1.65) for people with subclinical hyperthyroidism and 0.90 (95% CI, 0.77-1.05) for those with subclinical hypothyroidism, compared with those with normal thyroid function.

Most fractures occurred in either the hip (14.1%) or spine (13.8%), according to the researchers.

Limitations included a lack of thyroid function data during the follow-up period and lack of data on bone mineral density, the researchers wrote.
 

‘An important risk factor’

Endocrinologist Michael McClung, MD, founding and emeritus director of the Oregon Osteoporosis Center, Portland, who was not involved in the study, pointed out that both subclinical hypothyroidism and subclinical hyperthyroidism have been linked to greater risk for cardiovascular disease as well as fracture.

The new paper underscores that subclinical hyperthyroidism “should be included as an important risk factor” for fracture as well as cardiovascular risk, Dr. McClung said in an interview. In considering whether to treat osteoporosis, subclinical hyperthyroidism “may be enough to tip the balance in favor of pharmacological therapy,” he added.

Thyroid-stimulating hormone (TSH) tests to assess thyroid function are typically ordered only if a patient has symptoms of hyperthyroidism or hypothyroidism, Ms. Daya said. Depending on the cause and severity of a low TSH level, a physician may prescribe methimazole or radioactive iodine therapy to reduce the production of thyroxine, she said.

However, well-designed studies are needed to evaluate whether treatment of subclinical thyroid dysfunction reduces the risk for fracture or cardiovascular problems and assess downsides such as side effects, costs, and psychological harm, Dr. McClung noted.

The U.S. Preventive Services Task Force concluded in 2015 that the data were insufficient to recommend screening for thyroid dysfunction in adults without symptoms. As of a year ago, no new evidence has emerged to support an update, according to the task force’s website.

“Until those studies are available, selective screening of thyroid function should be considered in all patients undergoing risk assessment for cardiovascular disease or skeletal health,” Dr. McClung said.

The Atherosclerosis Risk in Communities Study has been funded by the National Heart, Lung, and Blood Institute of the National Institutes of Health (NIH) and the U.S. Department of Health and Human Services. Ms. Daya and four study authors reported receiving NIH grants during the study period. Dr. McClung reported no relevant financial conflicts of interest.

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

People with subclinical hyperthyroidism are at 34% greater risk of experiencing a fracture compared with those with normal thyroid function, new research shows.

The finding, from a study of nearly 11,000 middle-aged men and women followed for a median of 2 decades, “highlights a potential role for more aggressive screening and monitoring of patients with subclinical hyperthyroidism to prevent bone mineral disease,” the researchers wrote.

Primary care physicians “should be more aware of the risks for fracture among persons with subclinical hyperthyroidism in the ambulatory setting,” Natalie R. Daya, a PhD student in epidemiology at Johns Hopkins Bloomberg School of Public Health, Baltimore, and first author of the study, told this news organization.

Ms. Daya and her colleagues published their findings in JAMA Network Open.

 

Building on earlier findings

The results agree with previous work, including a meta-analysis of 13 prospective cohort studies of 70,289 primarily White individuals with an average age of 64 years, which found that subclinical hyperthyroidism was associated with a modestly increased risk for fractures, the researchers noted.

“Our study extends these findings to a younger, community-based cohort that included both Black and White participants, included extensive adjustment for potential confounders, and had a longer follow-up period (median follow-up of 21 years vs. 12 years),” they wrote.

The study included 10,946 participants in the Atherosclerosis Risk in Communities Study who were recruited in Washington County, Maryland; Forsyth County, North Carolina; Jackson, Mississippi; and the suburbs of Minneapolis.

Baseline thyroid function was measured in blood samples collected during the second visit, which occurred between 1990 and 1992. No participants in the new analysis took thyroid medications or had a history of hospitalization for fractures at baseline, and all identified as Black or White. The mean age was 57 years, 24% were Black, and 54.3% were female.

Subclinical hyperthyroidism was defined as a thyrotropin level less than 0.56 mIU/L; subclinical hypothyroidism as a thyrotropin level greater than 5.1 mIU/L; and normal thyroid function as a thyrotropin level between 0.56 and 5.1 mIU/L, with normal free thyroxine levels of 0.85-1.4 ng/dL.

The vast majority (93%) of participants had normal thyroid function, 2.6% had subclinical hyperthyroidism, and 4.4% had subclinical hypothyroidism, according to the researchers.

Median follow-up was 21 years. The researchers identified 3,556 incident fractures, detected with hospitalization discharge codes through 2019 and inpatient and Medicare claims data through 2018, for a rate of 167.1 per 10,000 person-years.

Adjusted hazard ratios for fracture were 1.34 (95% confidence interval [CI], 1.09-1.65) for people with subclinical hyperthyroidism and 0.90 (95% CI, 0.77-1.05) for those with subclinical hypothyroidism, compared with those with normal thyroid function.

Most fractures occurred in either the hip (14.1%) or spine (13.8%), according to the researchers.

Limitations included a lack of thyroid function data during the follow-up period and lack of data on bone mineral density, the researchers wrote.
 

‘An important risk factor’

Endocrinologist Michael McClung, MD, founding and emeritus director of the Oregon Osteoporosis Center, Portland, who was not involved in the study, pointed out that both subclinical hypothyroidism and subclinical hyperthyroidism have been linked to greater risk for cardiovascular disease as well as fracture.

The new paper underscores that subclinical hyperthyroidism “should be included as an important risk factor” for fracture as well as cardiovascular risk, Dr. McClung said in an interview. In considering whether to treat osteoporosis, subclinical hyperthyroidism “may be enough to tip the balance in favor of pharmacological therapy,” he added.

Thyroid-stimulating hormone (TSH) tests to assess thyroid function are typically ordered only if a patient has symptoms of hyperthyroidism or hypothyroidism, Ms. Daya said. Depending on the cause and severity of a low TSH level, a physician may prescribe methimazole or radioactive iodine therapy to reduce the production of thyroxine, she said.

However, well-designed studies are needed to evaluate whether treatment of subclinical thyroid dysfunction reduces the risk for fracture or cardiovascular problems and assess downsides such as side effects, costs, and psychological harm, Dr. McClung noted.

The U.S. Preventive Services Task Force concluded in 2015 that the data were insufficient to recommend screening for thyroid dysfunction in adults without symptoms. As of a year ago, no new evidence has emerged to support an update, according to the task force’s website.

“Until those studies are available, selective screening of thyroid function should be considered in all patients undergoing risk assessment for cardiovascular disease or skeletal health,” Dr. McClung said.

The Atherosclerosis Risk in Communities Study has been funded by the National Heart, Lung, and Blood Institute of the National Institutes of Health (NIH) and the U.S. Department of Health and Human Services. Ms. Daya and four study authors reported receiving NIH grants during the study period. Dr. McClung reported no relevant financial conflicts of interest.

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

Use of a combination antihypertensive product containing quarter doses of four different drugs could be an effective strategy to get patients to target blood pressures in one step, a new study suggests. 

The study, QUARTET-USA, showed a reduction in BP of almost 5 mm Hg more than the comparator of one antihypertensive agent at standard dose over the 12-week follow-up period in patients with mild to moderate hypertension.

The QUARTET-USA study was presented at the American Heart Association scientific sessions by Mark Huffman, MD, professor of medicine at Washington University in St. Louis. 

It builds on a previous trial, QUARTET, conducted in Australia, which first showed benefits with this approach.

In the new U.S. study, which was considerably smaller than the Australian trial, the four-drug combination, including candesartan, amlodipine, indapamide, and bisoprolol, led to a –4.8/–4.9 mm Hg greater reduction in BP from baseline to 12 weeks, compared with standard-dose candesartan monotherapy.

Differences in systolic BP were not statistically significant, which is likely because of limited power related to the sample size, Dr. Huffman noted.

Adverse events were more common in the four-drug intervention group, but the rate of discontinuation was higher in the comparator group. No severe adverse events were deemed related to the study drug.

“The direction and magnitude of [the] blood pressure–lowering effect were similar between the previous Australian study and this American study, despite different populations with lower baseline blood pressure in the current study, thus strengthening the case for this new approach,” Dr. Huffman concluded.

“The two studies together show that the approach of using four drugs in quarter doses is more effective in lowering blood pressure than a single standard dose antihypertensive agent and has an acceptable safely profile,” he said in an interview.

He said the four-drug combination could be an effective way of getting patients to target without multiple appointments.

“If you think about how many visits to the doctor’s office it takes to get patients to goal blood pressures, this combination gets patients down to new guideline target levels in one step, whereas in the SPRINT trial it took three or more visits to get down to these levels. And in practice we lose people – they don’t come back,” he said.

Dr. Huffman explained that the rationale for the study was the persistently low hypertension control rate, which demonstrates the need for a new approach.

The previous Australian QUARTET study suggested that ultra–low-dose combination therapy has a favorable balance between blood pressure–lowering effect, tolerability, and adherence.

That study, conducted in 591 patients and reported in 2021, demonstrated a greater BP-lowering effect with a four-drug combination at quarter doses (irbesartan 37.5 mg, amlodipine 1.25 mg, indapamide 0.625 mg, bisoprolol 2.5 mg) at 12 weeks, compared with irbesartan 150 mg daily. Systolic BP was reduced by more than 6.9 mm Hg and diastolic BP by 5.8 mm Hg than full-dose irbesartan alone, both significant differences.

The current study, QUARTET-USA, aimed to see if a similar strategy could produce comparable results in a U.S. population.

The U.S. study included 62 patients from the Access Community Health Network, Chicago, who were either treatment naive with BPs above 140/90 mm Hg, or already taking antihypertensive monotherapy with BPs above 130/85 mm Hg.

The mean systolic BP at baseline was 138 mm Hg and the mean diastolic pressure was 84 mm Hg.

Study participants were mainly from ethnic minorities (90% Hispanic or Black) and over half were from low-income households (annual household income less than $25,000).

They were randomly assigned to daily administration of a four-drug combination at quarter doses (candesartan 2 mg, amlodipine 1.25 mg, indapamide 0.625 mg, bisoprolol 2.5 mg) or a full dose of candesartan 8 mg (the comparator arm).

Amlodipine 5 mg daily could be added on to treatment if BP remained above 130/80 mm Hg at 6 weeks. This occurred in 18% of the study group versus 53% of the comparator group.

Results showed that at 12 weeks the adjusted mean change in systolic BP weeks was –4.8 mm Hg (95% CI,–10.7 to 1.2), and the adjusted mean change in diastolic BP was –4.9 mm Hg (95% CI, –8.6 to –1.1) in the four-drug combination group, compared with the comparator arm.

Average BPs at the end of 12-week study period were 121 mm Hg systolic and 73 mm Hg diastolic in the four-drug intervention group, compared with 124 mm Hg systolic and 77 mm Hg diastolic in the comparator group.

Any adverse events that were possibly related to drug therapy occurred in 25% of the intervention group versus 10% of the comparator group. But adverse events leading to discontinuation occurred in 6.3% of the study group versus 26.7% of patients in the comparator arm.

“New approaches are needed to achieve lower blood pressure targets, especially for patients and communities with a high burden of hypertension and hypertension-related diseases. QUARTET-USA was the first trial of a four-drug, ultra–low-dose, blood pressure–lowering combination therapy in the U.S.,” Dr. Huffman said.

“We showed reductions in blood pressure similar in magnitude to those in the Australian study. It is useful to know that the direction of the effect is similar across varied populations. Now that we have that signal of efficacy and tolerability, we can move to actually getting it into the hands of patients and providers,” he added.

Noting that further studies will be required to attain marketing authorization, Dr. Huffman suggested that a pharmaceutical company would need to complete that process.

“These are promising results for companies who may be interested in partnering,” he said.

‘A more efficient approach’ 

LaPrincess C. Brewer, MD, assistant professor of medicine at the Mayo Clinic, Rochester, Minn., and discussant of the study, said the QUARTET-USA study suggests the four-drug, low-dose combination shows promise in lowering BP, compared with the standard dose, and while the reduction in systolic BP was not quite significant, it was clinically meaningful.

“Most U.S. adults with hypertension do not have it under control. This is due to unfavorable social and structural determinants of health which limit adherence to antihypertensive medication,” Dr. Brewer noted.  

From a patient point of view, the multiple visits needed to attain goals are a burden and there is also the issue of clinical inertia and lack of medication intensification by clinicians, she commented. 

“Of patients with uncontrolled hypertension, 40% are taking just one antihypertensive medication, so up-front, low-dose combination therapy is likely a more efficient approach,” she said.

“This study builds the evidence base for the need for tailored interventions that address the social determinants of health and the intentional prioritization of diverse population in clinical trials,” Dr. Brewer concluded.

QUARTET was an investigator-initiated study, Dr. Huffman reported a pending patent for a heart failure polypill. The George Institute for Global Health, Sydney, Australia, where Huffman has a secondary appointment, has a patent, license, and has received investment funding with intent to commercialize fixed-dose combination therapy. Dr. Brewer reported research support from the National Institutes of Health, Centers for Disease Control and Prevention, American Heart Association, and Bristol-Meyers Squibb Foundation.

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

Use of a combination antihypertensive product containing quarter doses of four different drugs could be an effective strategy to get patients to target blood pressures in one step, a new study suggests. 

The study, QUARTET-USA, showed a reduction in BP of almost 5 mm Hg more than the comparator of one antihypertensive agent at standard dose over the 12-week follow-up period in patients with mild to moderate hypertension.

The QUARTET-USA study was presented at the American Heart Association scientific sessions by Mark Huffman, MD, professor of medicine at Washington University in St. Louis. 

It builds on a previous trial, QUARTET, conducted in Australia, which first showed benefits with this approach.

In the new U.S. study, which was considerably smaller than the Australian trial, the four-drug combination, including candesartan, amlodipine, indapamide, and bisoprolol, led to a –4.8/–4.9 mm Hg greater reduction in BP from baseline to 12 weeks, compared with standard-dose candesartan monotherapy.

Differences in systolic BP were not statistically significant, which is likely because of limited power related to the sample size, Dr. Huffman noted.

Adverse events were more common in the four-drug intervention group, but the rate of discontinuation was higher in the comparator group. No severe adverse events were deemed related to the study drug.

“The direction and magnitude of [the] blood pressure–lowering effect were similar between the previous Australian study and this American study, despite different populations with lower baseline blood pressure in the current study, thus strengthening the case for this new approach,” Dr. Huffman concluded.

“The two studies together show that the approach of using four drugs in quarter doses is more effective in lowering blood pressure than a single standard dose antihypertensive agent and has an acceptable safely profile,” he said in an interview.

He said the four-drug combination could be an effective way of getting patients to target without multiple appointments.

“If you think about how many visits to the doctor’s office it takes to get patients to goal blood pressures, this combination gets patients down to new guideline target levels in one step, whereas in the SPRINT trial it took three or more visits to get down to these levels. And in practice we lose people – they don’t come back,” he said.

Dr. Huffman explained that the rationale for the study was the persistently low hypertension control rate, which demonstrates the need for a new approach.

The previous Australian QUARTET study suggested that ultra–low-dose combination therapy has a favorable balance between blood pressure–lowering effect, tolerability, and adherence.

That study, conducted in 591 patients and reported in 2021, demonstrated a greater BP-lowering effect with a four-drug combination at quarter doses (irbesartan 37.5 mg, amlodipine 1.25 mg, indapamide 0.625 mg, bisoprolol 2.5 mg) at 12 weeks, compared with irbesartan 150 mg daily. Systolic BP was reduced by more than 6.9 mm Hg and diastolic BP by 5.8 mm Hg than full-dose irbesartan alone, both significant differences.

The current study, QUARTET-USA, aimed to see if a similar strategy could produce comparable results in a U.S. population.

The U.S. study included 62 patients from the Access Community Health Network, Chicago, who were either treatment naive with BPs above 140/90 mm Hg, or already taking antihypertensive monotherapy with BPs above 130/85 mm Hg.

The mean systolic BP at baseline was 138 mm Hg and the mean diastolic pressure was 84 mm Hg.

Study participants were mainly from ethnic minorities (90% Hispanic or Black) and over half were from low-income households (annual household income less than $25,000).

They were randomly assigned to daily administration of a four-drug combination at quarter doses (candesartan 2 mg, amlodipine 1.25 mg, indapamide 0.625 mg, bisoprolol 2.5 mg) or a full dose of candesartan 8 mg (the comparator arm).

Amlodipine 5 mg daily could be added on to treatment if BP remained above 130/80 mm Hg at 6 weeks. This occurred in 18% of the study group versus 53% of the comparator group.

Results showed that at 12 weeks the adjusted mean change in systolic BP weeks was –4.8 mm Hg (95% CI,–10.7 to 1.2), and the adjusted mean change in diastolic BP was –4.9 mm Hg (95% CI, –8.6 to –1.1) in the four-drug combination group, compared with the comparator arm.

Average BPs at the end of 12-week study period were 121 mm Hg systolic and 73 mm Hg diastolic in the four-drug intervention group, compared with 124 mm Hg systolic and 77 mm Hg diastolic in the comparator group.

Any adverse events that were possibly related to drug therapy occurred in 25% of the intervention group versus 10% of the comparator group. But adverse events leading to discontinuation occurred in 6.3% of the study group versus 26.7% of patients in the comparator arm.

“New approaches are needed to achieve lower blood pressure targets, especially for patients and communities with a high burden of hypertension and hypertension-related diseases. QUARTET-USA was the first trial of a four-drug, ultra–low-dose, blood pressure–lowering combination therapy in the U.S.,” Dr. Huffman said.

“We showed reductions in blood pressure similar in magnitude to those in the Australian study. It is useful to know that the direction of the effect is similar across varied populations. Now that we have that signal of efficacy and tolerability, we can move to actually getting it into the hands of patients and providers,” he added.

Noting that further studies will be required to attain marketing authorization, Dr. Huffman suggested that a pharmaceutical company would need to complete that process.

“These are promising results for companies who may be interested in partnering,” he said.

‘A more efficient approach’ 

LaPrincess C. Brewer, MD, assistant professor of medicine at the Mayo Clinic, Rochester, Minn., and discussant of the study, said the QUARTET-USA study suggests the four-drug, low-dose combination shows promise in lowering BP, compared with the standard dose, and while the reduction in systolic BP was not quite significant, it was clinically meaningful.

“Most U.S. adults with hypertension do not have it under control. This is due to unfavorable social and structural determinants of health which limit adherence to antihypertensive medication,” Dr. Brewer noted.  

From a patient point of view, the multiple visits needed to attain goals are a burden and there is also the issue of clinical inertia and lack of medication intensification by clinicians, she commented. 

“Of patients with uncontrolled hypertension, 40% are taking just one antihypertensive medication, so up-front, low-dose combination therapy is likely a more efficient approach,” she said.

“This study builds the evidence base for the need for tailored interventions that address the social determinants of health and the intentional prioritization of diverse population in clinical trials,” Dr. Brewer concluded.

QUARTET was an investigator-initiated study, Dr. Huffman reported a pending patent for a heart failure polypill. The George Institute for Global Health, Sydney, Australia, where Huffman has a secondary appointment, has a patent, license, and has received investment funding with intent to commercialize fixed-dose combination therapy. Dr. Brewer reported research support from the National Institutes of Health, Centers for Disease Control and Prevention, American Heart Association, and Bristol-Meyers Squibb Foundation.

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

Use of a combination antihypertensive product containing quarter doses of four different drugs could be an effective strategy to get patients to target blood pressures in one step, a new study suggests. 

The study, QUARTET-USA, showed a reduction in BP of almost 5 mm Hg more than the comparator of one antihypertensive agent at standard dose over the 12-week follow-up period in patients with mild to moderate hypertension.

The QUARTET-USA study was presented at the American Heart Association scientific sessions by Mark Huffman, MD, professor of medicine at Washington University in St. Louis. 

It builds on a previous trial, QUARTET, conducted in Australia, which first showed benefits with this approach.

In the new U.S. study, which was considerably smaller than the Australian trial, the four-drug combination, including candesartan, amlodipine, indapamide, and bisoprolol, led to a –4.8/–4.9 mm Hg greater reduction in BP from baseline to 12 weeks, compared with standard-dose candesartan monotherapy.

Differences in systolic BP were not statistically significant, which is likely because of limited power related to the sample size, Dr. Huffman noted.

Adverse events were more common in the four-drug intervention group, but the rate of discontinuation was higher in the comparator group. No severe adverse events were deemed related to the study drug.

“The direction and magnitude of [the] blood pressure–lowering effect were similar between the previous Australian study and this American study, despite different populations with lower baseline blood pressure in the current study, thus strengthening the case for this new approach,” Dr. Huffman concluded.

“The two studies together show that the approach of using four drugs in quarter doses is more effective in lowering blood pressure than a single standard dose antihypertensive agent and has an acceptable safely profile,” he said in an interview.

He said the four-drug combination could be an effective way of getting patients to target without multiple appointments.

“If you think about how many visits to the doctor’s office it takes to get patients to goal blood pressures, this combination gets patients down to new guideline target levels in one step, whereas in the SPRINT trial it took three or more visits to get down to these levels. And in practice we lose people – they don’t come back,” he said.

Dr. Huffman explained that the rationale for the study was the persistently low hypertension control rate, which demonstrates the need for a new approach.

The previous Australian QUARTET study suggested that ultra–low-dose combination therapy has a favorable balance between blood pressure–lowering effect, tolerability, and adherence.

That study, conducted in 591 patients and reported in 2021, demonstrated a greater BP-lowering effect with a four-drug combination at quarter doses (irbesartan 37.5 mg, amlodipine 1.25 mg, indapamide 0.625 mg, bisoprolol 2.5 mg) at 12 weeks, compared with irbesartan 150 mg daily. Systolic BP was reduced by more than 6.9 mm Hg and diastolic BP by 5.8 mm Hg than full-dose irbesartan alone, both significant differences.

The current study, QUARTET-USA, aimed to see if a similar strategy could produce comparable results in a U.S. population.

The U.S. study included 62 patients from the Access Community Health Network, Chicago, who were either treatment naive with BPs above 140/90 mm Hg, or already taking antihypertensive monotherapy with BPs above 130/85 mm Hg.

The mean systolic BP at baseline was 138 mm Hg and the mean diastolic pressure was 84 mm Hg.

Study participants were mainly from ethnic minorities (90% Hispanic or Black) and over half were from low-income households (annual household income less than $25,000).

They were randomly assigned to daily administration of a four-drug combination at quarter doses (candesartan 2 mg, amlodipine 1.25 mg, indapamide 0.625 mg, bisoprolol 2.5 mg) or a full dose of candesartan 8 mg (the comparator arm).

Amlodipine 5 mg daily could be added on to treatment if BP remained above 130/80 mm Hg at 6 weeks. This occurred in 18% of the study group versus 53% of the comparator group.

Results showed that at 12 weeks the adjusted mean change in systolic BP weeks was –4.8 mm Hg (95% CI,–10.7 to 1.2), and the adjusted mean change in diastolic BP was –4.9 mm Hg (95% CI, –8.6 to –1.1) in the four-drug combination group, compared with the comparator arm.

Average BPs at the end of 12-week study period were 121 mm Hg systolic and 73 mm Hg diastolic in the four-drug intervention group, compared with 124 mm Hg systolic and 77 mm Hg diastolic in the comparator group.

Any adverse events that were possibly related to drug therapy occurred in 25% of the intervention group versus 10% of the comparator group. But adverse events leading to discontinuation occurred in 6.3% of the study group versus 26.7% of patients in the comparator arm.

“New approaches are needed to achieve lower blood pressure targets, especially for patients and communities with a high burden of hypertension and hypertension-related diseases. QUARTET-USA was the first trial of a four-drug, ultra–low-dose, blood pressure–lowering combination therapy in the U.S.,” Dr. Huffman said.

“We showed reductions in blood pressure similar in magnitude to those in the Australian study. It is useful to know that the direction of the effect is similar across varied populations. Now that we have that signal of efficacy and tolerability, we can move to actually getting it into the hands of patients and providers,” he added.

Noting that further studies will be required to attain marketing authorization, Dr. Huffman suggested that a pharmaceutical company would need to complete that process.

“These are promising results for companies who may be interested in partnering,” he said.

‘A more efficient approach’ 

LaPrincess C. Brewer, MD, assistant professor of medicine at the Mayo Clinic, Rochester, Minn., and discussant of the study, said the QUARTET-USA study suggests the four-drug, low-dose combination shows promise in lowering BP, compared with the standard dose, and while the reduction in systolic BP was not quite significant, it was clinically meaningful.

“Most U.S. adults with hypertension do not have it under control. This is due to unfavorable social and structural determinants of health which limit adherence to antihypertensive medication,” Dr. Brewer noted.  

From a patient point of view, the multiple visits needed to attain goals are a burden and there is also the issue of clinical inertia and lack of medication intensification by clinicians, she commented. 

“Of patients with uncontrolled hypertension, 40% are taking just one antihypertensive medication, so up-front, low-dose combination therapy is likely a more efficient approach,” she said.

“This study builds the evidence base for the need for tailored interventions that address the social determinants of health and the intentional prioritization of diverse population in clinical trials,” Dr. Brewer concluded.

QUARTET was an investigator-initiated study, Dr. Huffman reported a pending patent for a heart failure polypill. The George Institute for Global Health, Sydney, Australia, where Huffman has a secondary appointment, has a patent, license, and has received investment funding with intent to commercialize fixed-dose combination therapy. Dr. Brewer reported research support from the National Institutes of Health, Centers for Disease Control and Prevention, American Heart Association, and Bristol-Meyers Squibb Foundation.

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

This year Medscape surveyed more than 2,300 physicians about how they prioritized various social issues. Around half of them rated climate change among their five most important issues. Slightly lower percentages of doctors prioritized domestic violence and immigration/refugee policies that highly, and about 40% did so regarding reproductive rights in the United States.

Survey responses and comments left on the Physicians’ Views on Today’s Divisive Social Issues 2022 report provide insights into doctors’ attitudes and thinking about these four social challenges.
 

Relevance of climate change to health care

In the Medscape report, 61% of physicians described themselves as “very concerned” or “concerned” about climate change, and about 7 in 10 agreed with the statement that it should be a top worldwide priority. “Climate change is the most pressing issue of this century,” a psychiatrist respondent wrote.

What about direct effects on patients’ health? An internist worried that rising temperatures will cause “pathogens to spread and infect disadvantaged people who do not have health access and have immunocompromised conditions.” A family medicine physician predicted “more weather disasters, more asthma, more hormonal changes, and more obesity.”

However, physician viewpoints ran the gamut with an issue that has become politically and emotionally charged. Descriptions such as “overblown,” “hysteria,” “hoax,” and “farce” were used. “Climate change is a natural phenomenon under God’s purview,” an emergency medicine physician said.

And there was some middle-ground thinking. “It’s overstated but quite real,” a pediatrician respondent wrote. Added an ophthalmologist: “It has gone on for ages. We must work to decrease man-made conditions that affect climate change, but it must be done in an intelligent fashion.”
 

Domestic violence: What physicians can do

About 7 in 10 physicians surveyed by Medscape said they don’t think the United States is adequately tackling domestic violence. “It is underrecognized and ignored,” a psychiatrist respondent argued. The problem is “rampant and unacceptable, pushed into a closet and normalized, with associated shame,” an emergency medicine doctor wrote.

Many respondents noted that physicians are under a mandate to report abuse of or a suspicious injury to a patient. Some shared anecdotes about how they reported action they had taken when they suspected it. “I’ve told patients who may be in dangerous situations that I’m a safe person and provide a safe space,” a radiologist added. An internist said, “I’ve recently started to ask about safety at home during triage on every patient.”

Other doctors bemoaned a lack of adequate education on detecting and managing domestic violence and abuse. “Domestic violence is often not recognized by health care providers,” a psychiatrist respondent observed.
 

Expanding legal immigration

In the Medscape report, 34% of physicians felt U.S. immigration/refugee policies need to be tougher, while 28% said they are too restrictive, and about a fifth saw them as appropriate.

“As an immigrant, I can tell you that the system is flawed and needs a complete overhaul, which will take a bipartisan effort,” an endocrinologist respondent wrote.

A number of respondents argued that it’s critical to simplify the process of obtaining U.S. citizenship so that fewer will feel forced to enter the country illegally. “For a country that relies very heavily on immigrants to sustain our health care system, we behave like idiots in denying safe harbor,” a nephrologist asserted.

A neurologist concurred. “Legal immigration needs to be encouraged. It should be easier to exchange visitor or student visa to immigrant visa in order to retain talent in the health care and technology fields, which would alleviate the shortage of workers in health care.”
 

Reproductive rights: No easy answers

Medscape’s survey was conducted before the U.S. Supreme Court in June reversed Roe v. Wade. In the report, 71% of physicians described themselves as very to somewhat concerned about women’s reproductive rights, but their viewpoints became nuanced after that. “There is a big disparity among physicians on this topic,” an oncologist respondent wrote.

At one end of the spectrum, 3% of doctors felt that abortions should never be permitted. “The human baby in the womb is an independent person with the right to life,” a pathologist said. At the other end, nearly one-fourth of physicians believed abortion should be accessible under all circumstances, regardless of trimester or reason. “I am just here to support the woman and make her decision a reality,” an internist said.

While saying an abortion should be granted after “fetal viability” only “in extenuating circumstances,” an ob.gyn. respondent said she is “extremely concerned” about attacks on abortion rights. “Some of us are old enough to remember women coming to the ER in extremis after illegal procedures, prior to Roe v. Wade.”

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

This year Medscape surveyed more than 2,300 physicians about how they prioritized various social issues. Around half of them rated climate change among their five most important issues. Slightly lower percentages of doctors prioritized domestic violence and immigration/refugee policies that highly, and about 40% did so regarding reproductive rights in the United States.

Survey responses and comments left on the Physicians’ Views on Today’s Divisive Social Issues 2022 report provide insights into doctors’ attitudes and thinking about these four social challenges.
 

Relevance of climate change to health care

In the Medscape report, 61% of physicians described themselves as “very concerned” or “concerned” about climate change, and about 7 in 10 agreed with the statement that it should be a top worldwide priority. “Climate change is the most pressing issue of this century,” a psychiatrist respondent wrote.

What about direct effects on patients’ health? An internist worried that rising temperatures will cause “pathogens to spread and infect disadvantaged people who do not have health access and have immunocompromised conditions.” A family medicine physician predicted “more weather disasters, more asthma, more hormonal changes, and more obesity.”

However, physician viewpoints ran the gamut with an issue that has become politically and emotionally charged. Descriptions such as “overblown,” “hysteria,” “hoax,” and “farce” were used. “Climate change is a natural phenomenon under God’s purview,” an emergency medicine physician said.

And there was some middle-ground thinking. “It’s overstated but quite real,” a pediatrician respondent wrote. Added an ophthalmologist: “It has gone on for ages. We must work to decrease man-made conditions that affect climate change, but it must be done in an intelligent fashion.”
 

Domestic violence: What physicians can do

About 7 in 10 physicians surveyed by Medscape said they don’t think the United States is adequately tackling domestic violence. “It is underrecognized and ignored,” a psychiatrist respondent argued. The problem is “rampant and unacceptable, pushed into a closet and normalized, with associated shame,” an emergency medicine doctor wrote.

Many respondents noted that physicians are under a mandate to report abuse of or a suspicious injury to a patient. Some shared anecdotes about how they reported action they had taken when they suspected it. “I’ve told patients who may be in dangerous situations that I’m a safe person and provide a safe space,” a radiologist added. An internist said, “I’ve recently started to ask about safety at home during triage on every patient.”

Other doctors bemoaned a lack of adequate education on detecting and managing domestic violence and abuse. “Domestic violence is often not recognized by health care providers,” a psychiatrist respondent observed.
 

Expanding legal immigration

In the Medscape report, 34% of physicians felt U.S. immigration/refugee policies need to be tougher, while 28% said they are too restrictive, and about a fifth saw them as appropriate.

“As an immigrant, I can tell you that the system is flawed and needs a complete overhaul, which will take a bipartisan effort,” an endocrinologist respondent wrote.

A number of respondents argued that it’s critical to simplify the process of obtaining U.S. citizenship so that fewer will feel forced to enter the country illegally. “For a country that relies very heavily on immigrants to sustain our health care system, we behave like idiots in denying safe harbor,” a nephrologist asserted.

A neurologist concurred. “Legal immigration needs to be encouraged. It should be easier to exchange visitor or student visa to immigrant visa in order to retain talent in the health care and technology fields, which would alleviate the shortage of workers in health care.”
 

Reproductive rights: No easy answers

Medscape’s survey was conducted before the U.S. Supreme Court in June reversed Roe v. Wade. In the report, 71% of physicians described themselves as very to somewhat concerned about women’s reproductive rights, but their viewpoints became nuanced after that. “There is a big disparity among physicians on this topic,” an oncologist respondent wrote.

At one end of the spectrum, 3% of doctors felt that abortions should never be permitted. “The human baby in the womb is an independent person with the right to life,” a pathologist said. At the other end, nearly one-fourth of physicians believed abortion should be accessible under all circumstances, regardless of trimester or reason. “I am just here to support the woman and make her decision a reality,” an internist said.

While saying an abortion should be granted after “fetal viability” only “in extenuating circumstances,” an ob.gyn. respondent said she is “extremely concerned” about attacks on abortion rights. “Some of us are old enough to remember women coming to the ER in extremis after illegal procedures, prior to Roe v. Wade.”

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

This year Medscape surveyed more than 2,300 physicians about how they prioritized various social issues. Around half of them rated climate change among their five most important issues. Slightly lower percentages of doctors prioritized domestic violence and immigration/refugee policies that highly, and about 40% did so regarding reproductive rights in the United States.

Survey responses and comments left on the Physicians’ Views on Today’s Divisive Social Issues 2022 report provide insights into doctors’ attitudes and thinking about these four social challenges.
 

Relevance of climate change to health care

In the Medscape report, 61% of physicians described themselves as “very concerned” or “concerned” about climate change, and about 7 in 10 agreed with the statement that it should be a top worldwide priority. “Climate change is the most pressing issue of this century,” a psychiatrist respondent wrote.

What about direct effects on patients’ health? An internist worried that rising temperatures will cause “pathogens to spread and infect disadvantaged people who do not have health access and have immunocompromised conditions.” A family medicine physician predicted “more weather disasters, more asthma, more hormonal changes, and more obesity.”

However, physician viewpoints ran the gamut with an issue that has become politically and emotionally charged. Descriptions such as “overblown,” “hysteria,” “hoax,” and “farce” were used. “Climate change is a natural phenomenon under God’s purview,” an emergency medicine physician said.

And there was some middle-ground thinking. “It’s overstated but quite real,” a pediatrician respondent wrote. Added an ophthalmologist: “It has gone on for ages. We must work to decrease man-made conditions that affect climate change, but it must be done in an intelligent fashion.”
 

Domestic violence: What physicians can do

About 7 in 10 physicians surveyed by Medscape said they don’t think the United States is adequately tackling domestic violence. “It is underrecognized and ignored,” a psychiatrist respondent argued. The problem is “rampant and unacceptable, pushed into a closet and normalized, with associated shame,” an emergency medicine doctor wrote.

Many respondents noted that physicians are under a mandate to report abuse of or a suspicious injury to a patient. Some shared anecdotes about how they reported action they had taken when they suspected it. “I’ve told patients who may be in dangerous situations that I’m a safe person and provide a safe space,” a radiologist added. An internist said, “I’ve recently started to ask about safety at home during triage on every patient.”

Other doctors bemoaned a lack of adequate education on detecting and managing domestic violence and abuse. “Domestic violence is often not recognized by health care providers,” a psychiatrist respondent observed.
 

Expanding legal immigration

In the Medscape report, 34% of physicians felt U.S. immigration/refugee policies need to be tougher, while 28% said they are too restrictive, and about a fifth saw them as appropriate.

“As an immigrant, I can tell you that the system is flawed and needs a complete overhaul, which will take a bipartisan effort,” an endocrinologist respondent wrote.

A number of respondents argued that it’s critical to simplify the process of obtaining U.S. citizenship so that fewer will feel forced to enter the country illegally. “For a country that relies very heavily on immigrants to sustain our health care system, we behave like idiots in denying safe harbor,” a nephrologist asserted.

A neurologist concurred. “Legal immigration needs to be encouraged. It should be easier to exchange visitor or student visa to immigrant visa in order to retain talent in the health care and technology fields, which would alleviate the shortage of workers in health care.”
 

Reproductive rights: No easy answers

Medscape’s survey was conducted before the U.S. Supreme Court in June reversed Roe v. Wade. In the report, 71% of physicians described themselves as very to somewhat concerned about women’s reproductive rights, but their viewpoints became nuanced after that. “There is a big disparity among physicians on this topic,” an oncologist respondent wrote.

At one end of the spectrum, 3% of doctors felt that abortions should never be permitted. “The human baby in the womb is an independent person with the right to life,” a pathologist said. At the other end, nearly one-fourth of physicians believed abortion should be accessible under all circumstances, regardless of trimester or reason. “I am just here to support the woman and make her decision a reality,” an internist said.

While saying an abortion should be granted after “fetal viability” only “in extenuating circumstances,” an ob.gyn. respondent said she is “extremely concerned” about attacks on abortion rights. “Some of us are old enough to remember women coming to the ER in extremis after illegal procedures, prior to Roe v. Wade.”

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

Staying mentally healthy is essential for everyone, and it’s vital for physicians. As medical professionals, you’re continually exposed to overwork, burnout, stressful situations, and challenging ethical decisions. Yet seeking help for mental health care may be last on your to-do list – or completely off your radar.

That’s sad and dangerous, since the American College of Emergency Physicians said 300-400 physicians die by suicide each year, and the stigma keeps 69% of female physicians from seeking mental health care, according to a prepandemic study.

In the 2022 Medscape Physician Suicide Report, 11% of female doctors and 9% of male doctors said they have had thoughts of suicide, and 64% experienced colloquial depression (feeling down, sad, or blue).

What’s more, physicians are typically seen as strong and capable and are often put on a pedestal by loved ones, patients, and the public and thought of as superhuman. No wonder it isn’t easy when you need to take time away to decompress and treat your mental well-being.

“There is a real fear for physicians when it comes to getting mental health care,” said Emil Tsai, MD, PhD, MAS, professor at the department of psychiatry and behavioral sciences at the University of California, Los Angeles, and an internationally reputed scientist in neurosciences and brain disorders.

The fear, said Dr. Tsai, comes from the stigma of mental health issues, potential repercussions to employment, and conceivable medical board suspension or revocation of your medical license.

Dr. Tsai said in an interview that to combat anxiety about “punishment” that many physicians fear when seeking care for their mental health, we must allow physicians to take time away from their day-to-day patient care for respite and treatment without reprisal.

Since the medical profession is high stress and has a high depression and suicide rate, finding solutions is imperative. And physicians must feel supported enough to seek treatment when needed. So how can we normalize seeking mental health care among physicians?
 

Get honest about stress and burnout

The only way to normalize any behavior is to be open and candid, Dr. Tsai said in an interview. The mental health conversation must occur across the board, not just within the medical profession.

“The greatest thing we can do to try and lift the burden that we place on physicians is to be willing to talk and be honest about the stress that physicians deal with and the importance of everyone feeling free to seek treatment and rest to strengthen their mental health,” said Dr. Tsai.

The more we talk about mental health and its treatment, the more we lessen the stigma, said Dr. Tsai. That could be more employer-employee check-ins, counseling as part of physician wellness, and programs structured so as not to construe a penal system.

“Mental health in the medical profession is a big issue and one that has to be met with the same compassion and care as it should be for any patient. We have annual physical checkups. Why don’t we offer annual mental health checkups for all, physicians included?” asked Dr. Tsai.
 

Evaluate the workload

Elizabeth Lombardo, PhD, psychologist, coach, and global keynote speaker, thinks that health care employers should reexamine their physicians’ workloads to see if they’re contributing to mental health issues.

The conversation on mental health in the workplace shouldn’t be about whether a certain person can handle stressors that are “normal” for health care settings. Instead, workplace managers in health care institutions should redefine workloads to ensure that physicians aren’t too heavily burdened with responsibilities that can cause overwork, burnout, and mental health problems,” she said.
 

Lessen the stigma

Even when physicians want to seek help for their psychological struggles, they may be weary of how their colleagues would react if they knew.

Raffaello Antonino, MD, clinical director at Therapy Central in London, said several underlying fears may exist at a physician’s core that prevent them from seeking care – being seen as weak, being judged as unfit to practice medicine, and the notion that “something is wrong with them.”

Dr. Antonino said we need to understand that physicians face challenges of bereavement and trauma derived from losing patients and the inability to save someone’s life. “These issues can easily develop into an accumulation of difficult, unprocessed emotions, later arising in symptoms and signs of PTSD, anxiety, and depression.”

Education is the best way to end this stigma, just like with any form of prejudice and stereotypes. For instance, we know that health care professionals are at risk of developing burnout. So, educating physicians on the symptoms and management of burnout and its consequences and prevention strategies is a must.

“Imagine what could happen if there were regular opportunities to work through the day’s events before signing out from a shift. The idea that individual weekly therapy is the only way to relieve mental distress is false,” said Lori McIsaac Bewsher, MSW, RSW, a trauma therapist and owner of a trauma-focused mental health clinic in New Brunswick.

“There are ways of integrating individual care into our doctor’s offices and hospitals that can be brief, effective, and confidential. The best way to introduce these interventions is early and collectively; no one is immune to the potential impact of exposure to trauma. The earlier these interventions can be accessed, the better the outcomes for everyone,” she said.

Dr. Antonino suggests, perhaps in the future, organizations can have “burnout checks” or mental health wellness checks for physicians akin to how we also have quick examinations for various physical ailments. What if physicians regularly answered a 10-question mental health survey as part of a burnout or trauma prevention strategy?

“Theirs is a profession and an identity which is often linked with a sense of strength, leadership and [benevolent] power: adjectives, which on the surface one might see as incompatible with what instead, unfortunately, and wrongly, may be associated with mental health issues,” said Dr. Antonino.
 

Keep it private

When it comes to removing the stigma from mental health care and treatment for physicians, privacy is top of mind. There needs to be some form of privacy protection for physicians who seek professional help for mental health reasons. Dr. Lombardo said physicians need to have the choice to keep their mental health journeys private. “Ideally, normalization should mean openly conversing about mental health, but for physicians, it can be a matter of life or death for their career, so the choice to remain private is something that should be afforded to them.”

Along those lines, the American Medical Association is pushing for system changes in legislative and regulatory arenas to support the mental health of practicing physicians, residents, and medical students. The organization is also urging health systems and state medical licensing bodies to remove questions on their applications that ask about prior treatment for mental health conditions.

Among many programs across the country, the Foundation of the Pennsylvania Medical Society has also created a Physicians’ Health Program, which provides confidential assessment, counseling, and referral services for physicians with mental health concerns.

“All of these initiatives are important in helping to destigmatize mental health issues among physicians,” said Harold Hong, MD, a board-certified psychiatrist in Raleigh, N.C.
 

Hail the benefits of treatment

Dr. Hong said to continue to destigmatize mental health among physicians and normalize its treatment, we not only have to emphasize how attending to mental health has individual benefits but also how it helps us help our patients.

“One key aspect that perhaps underpins this issue is the still present separation between mental and physical health, between mind and body, Dr. Hong said in an interview. “Feeling sad or angry or anxious should become a fact of life, a characteristic of being human, just like catching a cold or breaking a leg.”

It’s a normalization that, perhaps more than anything else, can lead the way for improving physicians’ mental health outcomes while also improving them for the rest of society. When society can finally see the health and well-being of someone in both their psychological and physical status, some of the stigmas may dissipate, and perhaps more physicians’ lives can be saved.

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

Staying mentally healthy is essential for everyone, and it’s vital for physicians. As medical professionals, you’re continually exposed to overwork, burnout, stressful situations, and challenging ethical decisions. Yet seeking help for mental health care may be last on your to-do list – or completely off your radar.

That’s sad and dangerous, since the American College of Emergency Physicians said 300-400 physicians die by suicide each year, and the stigma keeps 69% of female physicians from seeking mental health care, according to a prepandemic study.

In the 2022 Medscape Physician Suicide Report, 11% of female doctors and 9% of male doctors said they have had thoughts of suicide, and 64% experienced colloquial depression (feeling down, sad, or blue).

What’s more, physicians are typically seen as strong and capable and are often put on a pedestal by loved ones, patients, and the public and thought of as superhuman. No wonder it isn’t easy when you need to take time away to decompress and treat your mental well-being.

“There is a real fear for physicians when it comes to getting mental health care,” said Emil Tsai, MD, PhD, MAS, professor at the department of psychiatry and behavioral sciences at the University of California, Los Angeles, and an internationally reputed scientist in neurosciences and brain disorders.

The fear, said Dr. Tsai, comes from the stigma of mental health issues, potential repercussions to employment, and conceivable medical board suspension or revocation of your medical license.

Dr. Tsai said in an interview that to combat anxiety about “punishment” that many physicians fear when seeking care for their mental health, we must allow physicians to take time away from their day-to-day patient care for respite and treatment without reprisal.

Since the medical profession is high stress and has a high depression and suicide rate, finding solutions is imperative. And physicians must feel supported enough to seek treatment when needed. So how can we normalize seeking mental health care among physicians?
 

Get honest about stress and burnout

The only way to normalize any behavior is to be open and candid, Dr. Tsai said in an interview. The mental health conversation must occur across the board, not just within the medical profession.

“The greatest thing we can do to try and lift the burden that we place on physicians is to be willing to talk and be honest about the stress that physicians deal with and the importance of everyone feeling free to seek treatment and rest to strengthen their mental health,” said Dr. Tsai.

The more we talk about mental health and its treatment, the more we lessen the stigma, said Dr. Tsai. That could be more employer-employee check-ins, counseling as part of physician wellness, and programs structured so as not to construe a penal system.

“Mental health in the medical profession is a big issue and one that has to be met with the same compassion and care as it should be for any patient. We have annual physical checkups. Why don’t we offer annual mental health checkups for all, physicians included?” asked Dr. Tsai.
 

Evaluate the workload

Elizabeth Lombardo, PhD, psychologist, coach, and global keynote speaker, thinks that health care employers should reexamine their physicians’ workloads to see if they’re contributing to mental health issues.

The conversation on mental health in the workplace shouldn’t be about whether a certain person can handle stressors that are “normal” for health care settings. Instead, workplace managers in health care institutions should redefine workloads to ensure that physicians aren’t too heavily burdened with responsibilities that can cause overwork, burnout, and mental health problems,” she said.
 

Lessen the stigma

Even when physicians want to seek help for their psychological struggles, they may be weary of how their colleagues would react if they knew.

Raffaello Antonino, MD, clinical director at Therapy Central in London, said several underlying fears may exist at a physician’s core that prevent them from seeking care – being seen as weak, being judged as unfit to practice medicine, and the notion that “something is wrong with them.”

Dr. Antonino said we need to understand that physicians face challenges of bereavement and trauma derived from losing patients and the inability to save someone’s life. “These issues can easily develop into an accumulation of difficult, unprocessed emotions, later arising in symptoms and signs of PTSD, anxiety, and depression.”

Education is the best way to end this stigma, just like with any form of prejudice and stereotypes. For instance, we know that health care professionals are at risk of developing burnout. So, educating physicians on the symptoms and management of burnout and its consequences and prevention strategies is a must.

“Imagine what could happen if there were regular opportunities to work through the day’s events before signing out from a shift. The idea that individual weekly therapy is the only way to relieve mental distress is false,” said Lori McIsaac Bewsher, MSW, RSW, a trauma therapist and owner of a trauma-focused mental health clinic in New Brunswick.

“There are ways of integrating individual care into our doctor’s offices and hospitals that can be brief, effective, and confidential. The best way to introduce these interventions is early and collectively; no one is immune to the potential impact of exposure to trauma. The earlier these interventions can be accessed, the better the outcomes for everyone,” she said.

Dr. Antonino suggests, perhaps in the future, organizations can have “burnout checks” or mental health wellness checks for physicians akin to how we also have quick examinations for various physical ailments. What if physicians regularly answered a 10-question mental health survey as part of a burnout or trauma prevention strategy?

“Theirs is a profession and an identity which is often linked with a sense of strength, leadership and [benevolent] power: adjectives, which on the surface one might see as incompatible with what instead, unfortunately, and wrongly, may be associated with mental health issues,” said Dr. Antonino.
 

Keep it private

When it comes to removing the stigma from mental health care and treatment for physicians, privacy is top of mind. There needs to be some form of privacy protection for physicians who seek professional help for mental health reasons. Dr. Lombardo said physicians need to have the choice to keep their mental health journeys private. “Ideally, normalization should mean openly conversing about mental health, but for physicians, it can be a matter of life or death for their career, so the choice to remain private is something that should be afforded to them.”

Along those lines, the American Medical Association is pushing for system changes in legislative and regulatory arenas to support the mental health of practicing physicians, residents, and medical students. The organization is also urging health systems and state medical licensing bodies to remove questions on their applications that ask about prior treatment for mental health conditions.

Among many programs across the country, the Foundation of the Pennsylvania Medical Society has also created a Physicians’ Health Program, which provides confidential assessment, counseling, and referral services for physicians with mental health concerns.

“All of these initiatives are important in helping to destigmatize mental health issues among physicians,” said Harold Hong, MD, a board-certified psychiatrist in Raleigh, N.C.
 

Hail the benefits of treatment

Dr. Hong said to continue to destigmatize mental health among physicians and normalize its treatment, we not only have to emphasize how attending to mental health has individual benefits but also how it helps us help our patients.

“One key aspect that perhaps underpins this issue is the still present separation between mental and physical health, between mind and body, Dr. Hong said in an interview. “Feeling sad or angry or anxious should become a fact of life, a characteristic of being human, just like catching a cold or breaking a leg.”

It’s a normalization that, perhaps more than anything else, can lead the way for improving physicians’ mental health outcomes while also improving them for the rest of society. When society can finally see the health and well-being of someone in both their psychological and physical status, some of the stigmas may dissipate, and perhaps more physicians’ lives can be saved.

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

Staying mentally healthy is essential for everyone, and it’s vital for physicians. As medical professionals, you’re continually exposed to overwork, burnout, stressful situations, and challenging ethical decisions. Yet seeking help for mental health care may be last on your to-do list – or completely off your radar.

That’s sad and dangerous, since the American College of Emergency Physicians said 300-400 physicians die by suicide each year, and the stigma keeps 69% of female physicians from seeking mental health care, according to a prepandemic study.

In the 2022 Medscape Physician Suicide Report, 11% of female doctors and 9% of male doctors said they have had thoughts of suicide, and 64% experienced colloquial depression (feeling down, sad, or blue).

What’s more, physicians are typically seen as strong and capable and are often put on a pedestal by loved ones, patients, and the public and thought of as superhuman. No wonder it isn’t easy when you need to take time away to decompress and treat your mental well-being.

“There is a real fear for physicians when it comes to getting mental health care,” said Emil Tsai, MD, PhD, MAS, professor at the department of psychiatry and behavioral sciences at the University of California, Los Angeles, and an internationally reputed scientist in neurosciences and brain disorders.

The fear, said Dr. Tsai, comes from the stigma of mental health issues, potential repercussions to employment, and conceivable medical board suspension or revocation of your medical license.

Dr. Tsai said in an interview that to combat anxiety about “punishment” that many physicians fear when seeking care for their mental health, we must allow physicians to take time away from their day-to-day patient care for respite and treatment without reprisal.

Since the medical profession is high stress and has a high depression and suicide rate, finding solutions is imperative. And physicians must feel supported enough to seek treatment when needed. So how can we normalize seeking mental health care among physicians?
 

Get honest about stress and burnout

The only way to normalize any behavior is to be open and candid, Dr. Tsai said in an interview. The mental health conversation must occur across the board, not just within the medical profession.

“The greatest thing we can do to try and lift the burden that we place on physicians is to be willing to talk and be honest about the stress that physicians deal with and the importance of everyone feeling free to seek treatment and rest to strengthen their mental health,” said Dr. Tsai.

The more we talk about mental health and its treatment, the more we lessen the stigma, said Dr. Tsai. That could be more employer-employee check-ins, counseling as part of physician wellness, and programs structured so as not to construe a penal system.

“Mental health in the medical profession is a big issue and one that has to be met with the same compassion and care as it should be for any patient. We have annual physical checkups. Why don’t we offer annual mental health checkups for all, physicians included?” asked Dr. Tsai.
 

Evaluate the workload

Elizabeth Lombardo, PhD, psychologist, coach, and global keynote speaker, thinks that health care employers should reexamine their physicians’ workloads to see if they’re contributing to mental health issues.

The conversation on mental health in the workplace shouldn’t be about whether a certain person can handle stressors that are “normal” for health care settings. Instead, workplace managers in health care institutions should redefine workloads to ensure that physicians aren’t too heavily burdened with responsibilities that can cause overwork, burnout, and mental health problems,” she said.
 

Lessen the stigma

Even when physicians want to seek help for their psychological struggles, they may be weary of how their colleagues would react if they knew.

Raffaello Antonino, MD, clinical director at Therapy Central in London, said several underlying fears may exist at a physician’s core that prevent them from seeking care – being seen as weak, being judged as unfit to practice medicine, and the notion that “something is wrong with them.”

Dr. Antonino said we need to understand that physicians face challenges of bereavement and trauma derived from losing patients and the inability to save someone’s life. “These issues can easily develop into an accumulation of difficult, unprocessed emotions, later arising in symptoms and signs of PTSD, anxiety, and depression.”

Education is the best way to end this stigma, just like with any form of prejudice and stereotypes. For instance, we know that health care professionals are at risk of developing burnout. So, educating physicians on the symptoms and management of burnout and its consequences and prevention strategies is a must.

“Imagine what could happen if there were regular opportunities to work through the day’s events before signing out from a shift. The idea that individual weekly therapy is the only way to relieve mental distress is false,” said Lori McIsaac Bewsher, MSW, RSW, a trauma therapist and owner of a trauma-focused mental health clinic in New Brunswick.

“There are ways of integrating individual care into our doctor’s offices and hospitals that can be brief, effective, and confidential. The best way to introduce these interventions is early and collectively; no one is immune to the potential impact of exposure to trauma. The earlier these interventions can be accessed, the better the outcomes for everyone,” she said.

Dr. Antonino suggests, perhaps in the future, organizations can have “burnout checks” or mental health wellness checks for physicians akin to how we also have quick examinations for various physical ailments. What if physicians regularly answered a 10-question mental health survey as part of a burnout or trauma prevention strategy?

“Theirs is a profession and an identity which is often linked with a sense of strength, leadership and [benevolent] power: adjectives, which on the surface one might see as incompatible with what instead, unfortunately, and wrongly, may be associated with mental health issues,” said Dr. Antonino.
 

Keep it private

When it comes to removing the stigma from mental health care and treatment for physicians, privacy is top of mind. There needs to be some form of privacy protection for physicians who seek professional help for mental health reasons. Dr. Lombardo said physicians need to have the choice to keep their mental health journeys private. “Ideally, normalization should mean openly conversing about mental health, but for physicians, it can be a matter of life or death for their career, so the choice to remain private is something that should be afforded to them.”

Along those lines, the American Medical Association is pushing for system changes in legislative and regulatory arenas to support the mental health of practicing physicians, residents, and medical students. The organization is also urging health systems and state medical licensing bodies to remove questions on their applications that ask about prior treatment for mental health conditions.

Among many programs across the country, the Foundation of the Pennsylvania Medical Society has also created a Physicians’ Health Program, which provides confidential assessment, counseling, and referral services for physicians with mental health concerns.

“All of these initiatives are important in helping to destigmatize mental health issues among physicians,” said Harold Hong, MD, a board-certified psychiatrist in Raleigh, N.C.
 

Hail the benefits of treatment

Dr. Hong said to continue to destigmatize mental health among physicians and normalize its treatment, we not only have to emphasize how attending to mental health has individual benefits but also how it helps us help our patients.

“One key aspect that perhaps underpins this issue is the still present separation between mental and physical health, between mind and body, Dr. Hong said in an interview. “Feeling sad or angry or anxious should become a fact of life, a characteristic of being human, just like catching a cold or breaking a leg.”

It’s a normalization that, perhaps more than anything else, can lead the way for improving physicians’ mental health outcomes while also improving them for the rest of society. When society can finally see the health and well-being of someone in both their psychological and physical status, some of the stigmas may dissipate, and perhaps more physicians’ lives can be saved.

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

The National Resident Matching Program’s (NRMP) decision to nix a proposal for a 2-day medical resident matching process has left some students scratching their heads about why the organization discounted the opinions of the majority of respondents – mostly medical students, residents, and fellows – who supported the change.

The program’s decision comes after nearly 3 months of feedback from the public, medical students, and education community. Although about 60% of public respondents believed the change could reduce stress and allow students more time for momentous career decisions, the program’s board of directors decided the disadvantages were “of greater consequence,” according to a Oct. 28 statement.

Those disadvantages included introducing application or interview behaviors that could increase students’ stress; potentially identifying partially matched or unmatched applicants, which could lead to bias; and extending the match process time for those applicants.

In addition, members of 12 medical education and student organizations raised other concerns, such as the proposed change not addressing high application numbers, according to the statement. NRMP has reported record numbers of applicants over the past few years, typically with more applicants than available program slots.

“While the testimony gave nod to the positive aspects of the proposal ... there was substantially more concern voiced about the potential negative consequences identified in the public comments,” NRMP President and CEO Donna L. Lamb, DHSc, MBA, BSN, told this news organization. Some of those issues could not be addressed without further study, so the board decided not to proceed with the proposal, she explained.

The proposal would have separated the Main Residency Match into two phases and replaced the Supplemental Offer and Acceptance Program (SOAP), in which unmatched or partially matched applicants apply for unfilled residency positions. Under the proposed change, each phase would have operated the same way, from rank order lists and using a matching algorithm to a pair of Match Days instead of a single day.

The two-phase process would have given students who didn’t match more time to carefully weigh residency programs – they can apply to up to 45 placements as part of SOAP – that will guide their career path for the next few years, PGY-1 intern Asim A., who asked not to be identified further, told this news organization. The alternative is a hasty decision once students learn which residency spots are available, he added. “Applicants would have breathing room to make a more informed decision.”

Asim, who is Canadian, said he is participating in a transitional year in internal medicine in the hopes of being matched into internal medicine or psychiatry. He said Canada’s two-phase match is a “lot less stressful” than the U.S. system.

Meanwhile, students on Reddit’s medical school community also questioned NRMP’s decision.

“A significant majority of those surveyed thought it would be beneficial. But NRMP decides to not go through with it,” one Reddit user wrote. Another posted, “The one thing that could have improved the match and they chose not to do it.”

Others supported the decision to retain a 1-day match.

“I think this was the right call,” Bryan Carmody, MD, an outspoken medical education blogger, tweeted after learning of NRMP’s decision. Dr. Carmody, a pediatric nephrologist, previously expressed to this news organization misgivings about whether the two-phase match would make it difficult for programs to thoroughly review candidates and vice versa. He was concerned that it would compress the interview season and pressure programs to rapidly review applicants and conduct interviews.

More than 8,000 people responded to the public survey that began in August and ran for a month. Nearly two-thirds of the respondents (60%) were students, residents, or fellows. About 25% included faculty, program directors, and staff. Among the survey findings, respondents were equally divided between whether the two-phase match would be modestly advantageous (30%) or significantly advantageous (30%) compared to 20% who viewed it as modestly or significantly disadvantageous.

The NRMP said it would continue engaging with the community through focus groups and other means to improve the match experience and transition to residency.

“It is important to remember that a proposal is just that,” Dr. Lamb told this news orgnization, “an opportunity to discuss the pros and cons of an idea or framework ... and to mitigate unwanted consequences determined to be detrimental to learners and programs.”

The NRMP will involve the community in future discussions “to continue to give learners a voice,” she said.

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

The National Resident Matching Program’s (NRMP) decision to nix a proposal for a 2-day medical resident matching process has left some students scratching their heads about why the organization discounted the opinions of the majority of respondents – mostly medical students, residents, and fellows – who supported the change.

The program’s decision comes after nearly 3 months of feedback from the public, medical students, and education community. Although about 60% of public respondents believed the change could reduce stress and allow students more time for momentous career decisions, the program’s board of directors decided the disadvantages were “of greater consequence,” according to a Oct. 28 statement.

Those disadvantages included introducing application or interview behaviors that could increase students’ stress; potentially identifying partially matched or unmatched applicants, which could lead to bias; and extending the match process time for those applicants.

In addition, members of 12 medical education and student organizations raised other concerns, such as the proposed change not addressing high application numbers, according to the statement. NRMP has reported record numbers of applicants over the past few years, typically with more applicants than available program slots.

“While the testimony gave nod to the positive aspects of the proposal ... there was substantially more concern voiced about the potential negative consequences identified in the public comments,” NRMP President and CEO Donna L. Lamb, DHSc, MBA, BSN, told this news organization. Some of those issues could not be addressed without further study, so the board decided not to proceed with the proposal, she explained.

The proposal would have separated the Main Residency Match into two phases and replaced the Supplemental Offer and Acceptance Program (SOAP), in which unmatched or partially matched applicants apply for unfilled residency positions. Under the proposed change, each phase would have operated the same way, from rank order lists and using a matching algorithm to a pair of Match Days instead of a single day.

The two-phase process would have given students who didn’t match more time to carefully weigh residency programs – they can apply to up to 45 placements as part of SOAP – that will guide their career path for the next few years, PGY-1 intern Asim A., who asked not to be identified further, told this news organization. The alternative is a hasty decision once students learn which residency spots are available, he added. “Applicants would have breathing room to make a more informed decision.”

Asim, who is Canadian, said he is participating in a transitional year in internal medicine in the hopes of being matched into internal medicine or psychiatry. He said Canada’s two-phase match is a “lot less stressful” than the U.S. system.

Meanwhile, students on Reddit’s medical school community also questioned NRMP’s decision.

“A significant majority of those surveyed thought it would be beneficial. But NRMP decides to not go through with it,” one Reddit user wrote. Another posted, “The one thing that could have improved the match and they chose not to do it.”

Others supported the decision to retain a 1-day match.

“I think this was the right call,” Bryan Carmody, MD, an outspoken medical education blogger, tweeted after learning of NRMP’s decision. Dr. Carmody, a pediatric nephrologist, previously expressed to this news organization misgivings about whether the two-phase match would make it difficult for programs to thoroughly review candidates and vice versa. He was concerned that it would compress the interview season and pressure programs to rapidly review applicants and conduct interviews.

More than 8,000 people responded to the public survey that began in August and ran for a month. Nearly two-thirds of the respondents (60%) were students, residents, or fellows. About 25% included faculty, program directors, and staff. Among the survey findings, respondents were equally divided between whether the two-phase match would be modestly advantageous (30%) or significantly advantageous (30%) compared to 20% who viewed it as modestly or significantly disadvantageous.

The NRMP said it would continue engaging with the community through focus groups and other means to improve the match experience and transition to residency.

“It is important to remember that a proposal is just that,” Dr. Lamb told this news orgnization, “an opportunity to discuss the pros and cons of an idea or framework ... and to mitigate unwanted consequences determined to be detrimental to learners and programs.”

The NRMP will involve the community in future discussions “to continue to give learners a voice,” she said.

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

The National Resident Matching Program’s (NRMP) decision to nix a proposal for a 2-day medical resident matching process has left some students scratching their heads about why the organization discounted the opinions of the majority of respondents – mostly medical students, residents, and fellows – who supported the change.

The program’s decision comes after nearly 3 months of feedback from the public, medical students, and education community. Although about 60% of public respondents believed the change could reduce stress and allow students more time for momentous career decisions, the program’s board of directors decided the disadvantages were “of greater consequence,” according to a Oct. 28 statement.

Those disadvantages included introducing application or interview behaviors that could increase students’ stress; potentially identifying partially matched or unmatched applicants, which could lead to bias; and extending the match process time for those applicants.

In addition, members of 12 medical education and student organizations raised other concerns, such as the proposed change not addressing high application numbers, according to the statement. NRMP has reported record numbers of applicants over the past few years, typically with more applicants than available program slots.

“While the testimony gave nod to the positive aspects of the proposal ... there was substantially more concern voiced about the potential negative consequences identified in the public comments,” NRMP President and CEO Donna L. Lamb, DHSc, MBA, BSN, told this news organization. Some of those issues could not be addressed without further study, so the board decided not to proceed with the proposal, she explained.

The proposal would have separated the Main Residency Match into two phases and replaced the Supplemental Offer and Acceptance Program (SOAP), in which unmatched or partially matched applicants apply for unfilled residency positions. Under the proposed change, each phase would have operated the same way, from rank order lists and using a matching algorithm to a pair of Match Days instead of a single day.

The two-phase process would have given students who didn’t match more time to carefully weigh residency programs – they can apply to up to 45 placements as part of SOAP – that will guide their career path for the next few years, PGY-1 intern Asim A., who asked not to be identified further, told this news organization. The alternative is a hasty decision once students learn which residency spots are available, he added. “Applicants would have breathing room to make a more informed decision.”

Asim, who is Canadian, said he is participating in a transitional year in internal medicine in the hopes of being matched into internal medicine or psychiatry. He said Canada’s two-phase match is a “lot less stressful” than the U.S. system.

Meanwhile, students on Reddit’s medical school community also questioned NRMP’s decision.

“A significant majority of those surveyed thought it would be beneficial. But NRMP decides to not go through with it,” one Reddit user wrote. Another posted, “The one thing that could have improved the match and they chose not to do it.”

Others supported the decision to retain a 1-day match.

“I think this was the right call,” Bryan Carmody, MD, an outspoken medical education blogger, tweeted after learning of NRMP’s decision. Dr. Carmody, a pediatric nephrologist, previously expressed to this news organization misgivings about whether the two-phase match would make it difficult for programs to thoroughly review candidates and vice versa. He was concerned that it would compress the interview season and pressure programs to rapidly review applicants and conduct interviews.

More than 8,000 people responded to the public survey that began in August and ran for a month. Nearly two-thirds of the respondents (60%) were students, residents, or fellows. About 25% included faculty, program directors, and staff. Among the survey findings, respondents were equally divided between whether the two-phase match would be modestly advantageous (30%) or significantly advantageous (30%) compared to 20% who viewed it as modestly or significantly disadvantageous.

The NRMP said it would continue engaging with the community through focus groups and other means to improve the match experience and transition to residency.

“It is important to remember that a proposal is just that,” Dr. Lamb told this news orgnization, “an opportunity to discuss the pros and cons of an idea or framework ... and to mitigate unwanted consequences determined to be detrimental to learners and programs.”

The NRMP will involve the community in future discussions “to continue to give learners a voice,” she said.

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

CHICAGO – In patients with chronic limb-threatening ischemia (CLTI) and a usable saphenous vein segment, a surgical procedure leads to better outcomes than an endovascular approach, according results of the multinational randomized BEST-CLI trial.

In that study, conducted with two cohorts, the advantage of surgery was limited to the group with an available saphenous vein, but in this group the advantage over an endovascular approach was substantial, according to Alik Farber, MD, chief of vascular and endovascular surgery at Boston University.

Ted Bosworth/MDedge News

“Bypass with adequate saphenous vein should be offered as a first-line treatment option for suitable candidates with CLTI as part of fully informed, shared decision-making,” Dr. Farber stated in presenting the results at the annual scientific sessions of the American Heart Association.

The study pursued two hypotheses, which is why CLTI patients were divided into two cohorts. For cohort 1, which was limited to CLTI patients with an available saphenous vein, it was predicted that surgery would be better than an endovascular approach. For cohort 2, which enrolled patients who needed an alternative conduit, the hypothesis was that endovascular procedures would prove superior.

The study confirmed the first hypothesis, but there was no difference between the two approaches for the composite primary outcome of major adverse limb events (MALE) in the second cohort.
 

Saphenous vein availability determined cohort

Candidates for the BEST-CLI (Best Endovascular versus Best Surgical Therapy in Patients with CLTI) trial had to have CLTI producing severe ischemia and to be judged by both surgeons and cardiovascular specialists to be candidates for both types of interventions. Eligible patients were then enrolled in cohort 1 if the saphenous vein was considered the best conduit on imaging. If not, they were enrolled in cohort 2.

Patients were randomized to undergo surgical or endovascular repair only after the cohort was assigned. The primary composite MALE endpoint consisted of an adjudicated first major reintervention, such as new bypass or thrombectomy, an above-the-ankle amputation, or death from any cause.

In cohort 1, the primary composite MALE endpoint was reached in 42.6% of those in surgical arm and 57.4% in the endovascular arm, translating into a 32% relative risk reduction (hazard ratio, 0.68; P < .001) in favor of surgery at the end of a median of 2.7 years of follow-up.

The main advantage was the difference in reinterventions. The lower rate in the surgical group (9.2% vs. 23.5%), translated into a 65% relative risk reduction for this endpoint (HR, 035; P < .001).

The reduction in above-ankle amputations in the surgical group (10.4% vs. 14.9%) was also significant (HR, 0.73; P = .04), but the reduction in all-cause mortality (33.0% vs. 37.6%) was not (HR, 0.98; P = .81).

BEST-CLI involved 150 sites in North America, Europe, and New Zealand. Cohort 1, which randomized 1,434 patients, was the larger of the two. In the second cohort, only 396 patients were randomized, which Dr. Farber said “might have been underpowered.”

The results were published in the New England Journal of Medicine simultaneously with presentation of the results at the meeting.

After a median follow-up of 1.6 years in cohort 2, the slightly lower proportion of patients who reached the composite MALE endpoint in the surgical group relative to the endovascular group (42.8% vs. 47.7%) did not translate into a significant advantage (HR, 0.79; P = .12).

For the individual components, the lower rate of reinterventions in the surgical arm (14.4% vs. 25.6%) did reach statistical significance (HR, 0.47; P = .002), but both amputation (14.9% vs. 14.1%) and all-cause death (26.3% vs. 24.1%) were numerically but not significantly higher in the surgical group.

The primary safety endpoint was major adverse cardiovascular events (MACE). This was not significantly different in either cohort. There were also no major differences between groups in the risk of perioperative complications.

Level 1 evidence provided for intervention choice

Overall, BEST-CLI showed that both surgical and endovascular revascularizations are effective and safe, according to Dr. Farber. As a result, he suggested that both can be considered even if a saphenous vein is available when specific patient characteristics make one more attractive than another.

Yet, in a general population with an available saphenous vein, these data provide “level 1 evidence” that a surgical approach should be the dominant choice, he added.

Ted Bosworth/MDedge News

A quality of life (QOL) substudy of BEST-CLI did not challenge this conclusion. Rather, the main finding was that restoring circulation by either approach has a major favorable impact on patient well-being, according to Matthew Menard, MD, codirector of endovascular surgery at Brigham and Women’s Hospital, Boston.

In this substudy, presented separately from the primary BEST-CLI results, that analysis confirmed that baseline QOL was extremely poor, whether measured with a disease specific instrument such as VascuQol, or generic instruments, such as SF-12.

Surgical or endovascular treatment produced clinically meaningful and sustained improvements in every QOL measure employed, according to Dr. Menard, and this was true in either cohort.
 

Results not necessarily relevant to all

These data are likely relevant to the patients evaluated, but “it is important to consider who made it into this trial,” according to Naomi M. Hamburg, MD, section chief of vascular biology at Boston University.

Ted Bosworth/MDedge News

Not least, patients had to be candidates for either surgical or endovascular repair to get into the study, omitting those patients not deemed by the investigators to be suited for either.

In addition, Dr. Hamburg pointed out that there was a low enrollment of Blacks (20%) and women (28%), two groups for whom CTLI is a common condition.

Lastly, Dr Hamburg questioned whether specific types of anatomy might be better suited to one procedure relative to another, a variable not considered in this study. Reassured by Dr. Farber that this will be explored in subsequent analyses of BEST-CLI data, Dr. Hamburg expressed interest in learning the results.

Dr. Hamburg was among those who spoke about the growing urgency to optimize strategies for early diagnosis and treatment of CTLI. She plugged the PAD National Action Plan as one of the efforts to thwart the coming wave of CTLI expected from the steep climb in the prevalence of diabetes in the United States.

Dr. Farber reported a financial relationship with Sanifit Therapeutics. The study was funded by the National Heart, Lung, and Blood Institute, but received additional support from multiple pharmaceutical companies. Dr. Menard reported a financial relationship with Janssen Pharmaceuticals. Dr. Hamburg reported financial relationships with Acceleron Pharma, Merck, NovoNordisk, and Sanifit.

CHICAGO – In patients with chronic limb-threatening ischemia (CLTI) and a usable saphenous vein segment, a surgical procedure leads to better outcomes than an endovascular approach, according results of the multinational randomized BEST-CLI trial.

In that study, conducted with two cohorts, the advantage of surgery was limited to the group with an available saphenous vein, but in this group the advantage over an endovascular approach was substantial, according to Alik Farber, MD, chief of vascular and endovascular surgery at Boston University.

Ted Bosworth/MDedge News

“Bypass with adequate saphenous vein should be offered as a first-line treatment option for suitable candidates with CLTI as part of fully informed, shared decision-making,” Dr. Farber stated in presenting the results at the annual scientific sessions of the American Heart Association.

The study pursued two hypotheses, which is why CLTI patients were divided into two cohorts. For cohort 1, which was limited to CLTI patients with an available saphenous vein, it was predicted that surgery would be better than an endovascular approach. For cohort 2, which enrolled patients who needed an alternative conduit, the hypothesis was that endovascular procedures would prove superior.

The study confirmed the first hypothesis, but there was no difference between the two approaches for the composite primary outcome of major adverse limb events (MALE) in the second cohort.
 

Saphenous vein availability determined cohort

Candidates for the BEST-CLI (Best Endovascular versus Best Surgical Therapy in Patients with CLTI) trial had to have CLTI producing severe ischemia and to be judged by both surgeons and cardiovascular specialists to be candidates for both types of interventions. Eligible patients were then enrolled in cohort 1 if the saphenous vein was considered the best conduit on imaging. If not, they were enrolled in cohort 2.

Patients were randomized to undergo surgical or endovascular repair only after the cohort was assigned. The primary composite MALE endpoint consisted of an adjudicated first major reintervention, such as new bypass or thrombectomy, an above-the-ankle amputation, or death from any cause.

In cohort 1, the primary composite MALE endpoint was reached in 42.6% of those in surgical arm and 57.4% in the endovascular arm, translating into a 32% relative risk reduction (hazard ratio, 0.68; P < .001) in favor of surgery at the end of a median of 2.7 years of follow-up.

The main advantage was the difference in reinterventions. The lower rate in the surgical group (9.2% vs. 23.5%), translated into a 65% relative risk reduction for this endpoint (HR, 035; P < .001).

The reduction in above-ankle amputations in the surgical group (10.4% vs. 14.9%) was also significant (HR, 0.73; P = .04), but the reduction in all-cause mortality (33.0% vs. 37.6%) was not (HR, 0.98; P = .81).

BEST-CLI involved 150 sites in North America, Europe, and New Zealand. Cohort 1, which randomized 1,434 patients, was the larger of the two. In the second cohort, only 396 patients were randomized, which Dr. Farber said “might have been underpowered.”

The results were published in the New England Journal of Medicine simultaneously with presentation of the results at the meeting.

After a median follow-up of 1.6 years in cohort 2, the slightly lower proportion of patients who reached the composite MALE endpoint in the surgical group relative to the endovascular group (42.8% vs. 47.7%) did not translate into a significant advantage (HR, 0.79; P = .12).

For the individual components, the lower rate of reinterventions in the surgical arm (14.4% vs. 25.6%) did reach statistical significance (HR, 0.47; P = .002), but both amputation (14.9% vs. 14.1%) and all-cause death (26.3% vs. 24.1%) were numerically but not significantly higher in the surgical group.

The primary safety endpoint was major adverse cardiovascular events (MACE). This was not significantly different in either cohort. There were also no major differences between groups in the risk of perioperative complications.

Level 1 evidence provided for intervention choice

Overall, BEST-CLI showed that both surgical and endovascular revascularizations are effective and safe, according to Dr. Farber. As a result, he suggested that both can be considered even if a saphenous vein is available when specific patient characteristics make one more attractive than another.

Yet, in a general population with an available saphenous vein, these data provide “level 1 evidence” that a surgical approach should be the dominant choice, he added.

Ted Bosworth/MDedge News

A quality of life (QOL) substudy of BEST-CLI did not challenge this conclusion. Rather, the main finding was that restoring circulation by either approach has a major favorable impact on patient well-being, according to Matthew Menard, MD, codirector of endovascular surgery at Brigham and Women’s Hospital, Boston.

In this substudy, presented separately from the primary BEST-CLI results, that analysis confirmed that baseline QOL was extremely poor, whether measured with a disease specific instrument such as VascuQol, or generic instruments, such as SF-12.

Surgical or endovascular treatment produced clinically meaningful and sustained improvements in every QOL measure employed, according to Dr. Menard, and this was true in either cohort.
 

Results not necessarily relevant to all

These data are likely relevant to the patients evaluated, but “it is important to consider who made it into this trial,” according to Naomi M. Hamburg, MD, section chief of vascular biology at Boston University.

Ted Bosworth/MDedge News

Not least, patients had to be candidates for either surgical or endovascular repair to get into the study, omitting those patients not deemed by the investigators to be suited for either.

In addition, Dr. Hamburg pointed out that there was a low enrollment of Blacks (20%) and women (28%), two groups for whom CTLI is a common condition.

Lastly, Dr Hamburg questioned whether specific types of anatomy might be better suited to one procedure relative to another, a variable not considered in this study. Reassured by Dr. Farber that this will be explored in subsequent analyses of BEST-CLI data, Dr. Hamburg expressed interest in learning the results.

Dr. Hamburg was among those who spoke about the growing urgency to optimize strategies for early diagnosis and treatment of CTLI. She plugged the PAD National Action Plan as one of the efforts to thwart the coming wave of CTLI expected from the steep climb in the prevalence of diabetes in the United States.

Dr. Farber reported a financial relationship with Sanifit Therapeutics. The study was funded by the National Heart, Lung, and Blood Institute, but received additional support from multiple pharmaceutical companies. Dr. Menard reported a financial relationship with Janssen Pharmaceuticals. Dr. Hamburg reported financial relationships with Acceleron Pharma, Merck, NovoNordisk, and Sanifit.

CHICAGO – In patients with chronic limb-threatening ischemia (CLTI) and a usable saphenous vein segment, a surgical procedure leads to better outcomes than an endovascular approach, according results of the multinational randomized BEST-CLI trial.

In that study, conducted with two cohorts, the advantage of surgery was limited to the group with an available saphenous vein, but in this group the advantage over an endovascular approach was substantial, according to Alik Farber, MD, chief of vascular and endovascular surgery at Boston University.

Ted Bosworth/MDedge News

“Bypass with adequate saphenous vein should be offered as a first-line treatment option for suitable candidates with CLTI as part of fully informed, shared decision-making,” Dr. Farber stated in presenting the results at the annual scientific sessions of the American Heart Association.

The study pursued two hypotheses, which is why CLTI patients were divided into two cohorts. For cohort 1, which was limited to CLTI patients with an available saphenous vein, it was predicted that surgery would be better than an endovascular approach. For cohort 2, which enrolled patients who needed an alternative conduit, the hypothesis was that endovascular procedures would prove superior.

The study confirmed the first hypothesis, but there was no difference between the two approaches for the composite primary outcome of major adverse limb events (MALE) in the second cohort.
 

Saphenous vein availability determined cohort

Candidates for the BEST-CLI (Best Endovascular versus Best Surgical Therapy in Patients with CLTI) trial had to have CLTI producing severe ischemia and to be judged by both surgeons and cardiovascular specialists to be candidates for both types of interventions. Eligible patients were then enrolled in cohort 1 if the saphenous vein was considered the best conduit on imaging. If not, they were enrolled in cohort 2.

Patients were randomized to undergo surgical or endovascular repair only after the cohort was assigned. The primary composite MALE endpoint consisted of an adjudicated first major reintervention, such as new bypass or thrombectomy, an above-the-ankle amputation, or death from any cause.

In cohort 1, the primary composite MALE endpoint was reached in 42.6% of those in surgical arm and 57.4% in the endovascular arm, translating into a 32% relative risk reduction (hazard ratio, 0.68; P < .001) in favor of surgery at the end of a median of 2.7 years of follow-up.

The main advantage was the difference in reinterventions. The lower rate in the surgical group (9.2% vs. 23.5%), translated into a 65% relative risk reduction for this endpoint (HR, 035; P < .001).

The reduction in above-ankle amputations in the surgical group (10.4% vs. 14.9%) was also significant (HR, 0.73; P = .04), but the reduction in all-cause mortality (33.0% vs. 37.6%) was not (HR, 0.98; P = .81).

BEST-CLI involved 150 sites in North America, Europe, and New Zealand. Cohort 1, which randomized 1,434 patients, was the larger of the two. In the second cohort, only 396 patients were randomized, which Dr. Farber said “might have been underpowered.”

The results were published in the New England Journal of Medicine simultaneously with presentation of the results at the meeting.

After a median follow-up of 1.6 years in cohort 2, the slightly lower proportion of patients who reached the composite MALE endpoint in the surgical group relative to the endovascular group (42.8% vs. 47.7%) did not translate into a significant advantage (HR, 0.79; P = .12).

For the individual components, the lower rate of reinterventions in the surgical arm (14.4% vs. 25.6%) did reach statistical significance (HR, 0.47; P = .002), but both amputation (14.9% vs. 14.1%) and all-cause death (26.3% vs. 24.1%) were numerically but not significantly higher in the surgical group.

The primary safety endpoint was major adverse cardiovascular events (MACE). This was not significantly different in either cohort. There were also no major differences between groups in the risk of perioperative complications.

Level 1 evidence provided for intervention choice

Overall, BEST-CLI showed that both surgical and endovascular revascularizations are effective and safe, according to Dr. Farber. As a result, he suggested that both can be considered even if a saphenous vein is available when specific patient characteristics make one more attractive than another.

Yet, in a general population with an available saphenous vein, these data provide “level 1 evidence” that a surgical approach should be the dominant choice, he added.

Ted Bosworth/MDedge News

A quality of life (QOL) substudy of BEST-CLI did not challenge this conclusion. Rather, the main finding was that restoring circulation by either approach has a major favorable impact on patient well-being, according to Matthew Menard, MD, codirector of endovascular surgery at Brigham and Women’s Hospital, Boston.

In this substudy, presented separately from the primary BEST-CLI results, that analysis confirmed that baseline QOL was extremely poor, whether measured with a disease specific instrument such as VascuQol, or generic instruments, such as SF-12.

Surgical or endovascular treatment produced clinically meaningful and sustained improvements in every QOL measure employed, according to Dr. Menard, and this was true in either cohort.
 

Results not necessarily relevant to all

These data are likely relevant to the patients evaluated, but “it is important to consider who made it into this trial,” according to Naomi M. Hamburg, MD, section chief of vascular biology at Boston University.

Ted Bosworth/MDedge News

Not least, patients had to be candidates for either surgical or endovascular repair to get into the study, omitting those patients not deemed by the investigators to be suited for either.

In addition, Dr. Hamburg pointed out that there was a low enrollment of Blacks (20%) and women (28%), two groups for whom CTLI is a common condition.

Lastly, Dr Hamburg questioned whether specific types of anatomy might be better suited to one procedure relative to another, a variable not considered in this study. Reassured by Dr. Farber that this will be explored in subsequent analyses of BEST-CLI data, Dr. Hamburg expressed interest in learning the results.

Dr. Hamburg was among those who spoke about the growing urgency to optimize strategies for early diagnosis and treatment of CTLI. She plugged the PAD National Action Plan as one of the efforts to thwart the coming wave of CTLI expected from the steep climb in the prevalence of diabetes in the United States.

Dr. Farber reported a financial relationship with Sanifit Therapeutics. The study was funded by the National Heart, Lung, and Blood Institute, but received additional support from multiple pharmaceutical companies. Dr. Menard reported a financial relationship with Janssen Pharmaceuticals. Dr. Hamburg reported financial relationships with Acceleron Pharma, Merck, NovoNordisk, and Sanifit.

Among people with nonalcoholic fatty liver disease (NAFLD), the fibrosis progression rate was higher among those who also had diabetes, according to new findings presented at the annual meeting of the American Association for the Study of Liver Diseases.

NAFLD patients with type 2 diabetes progressed by one stage about every 6 years, compared with one stage about every 8 years among patients without diabetes, said Daniel Huang, MBBS, a visiting scholar at the University of California San Diego (UCSD) NAFLD Research Center and a transplant hepatologist at National University Hospital in Singapore.

“We now know that fibrosis stage is a major determinant of liver-related outcomes in NAFLD, as well as overall mortality,” he said. “Liver fibrosis progresses by approximately one stage every 7 years for individuals with NASH (nonalcoholic steatohepatitis).”

Recent UCSD data have indicated that about 14% of patients over age 50 with type 2 diabetes have NAFLD with advanced fibrosis, he noted. Previous studies have shown that diabetes is associated with higher rates of advanced fibrosis, cirrhosis, and hepatocellular carcinoma, but limited data exist around whether the fibrosis progression rate is higher among diabetics.
 

National study cohort

Dr. Huang and colleagues conducted a multicenter, multiethnic prospective cohort study within the NASH Clinical Research Network consortium to examine the fibrosis progression rate and the fibrosis regression rate among patients with or without diabetes. The study included adult participants at eight sites across the United States who had biopsy-confirmed NAFLD and available paired liver biopsies that were at least 1 year apart.

Clinical and laboratory data were obtained at enrollment and prospectively at 48-week intervals and recorded at the time of any liver biopsies. A central pathology committee conducted the liver histology assessment, and the entire pathology committee was blinded to clinical data and the sequence of liver biopsy. The fibrosis progression and regression rates were defined as the change in fibrosis stage over time between biopsies, measured in years.

The study comprised 447 adult participants with NAFLD: 208 patients with type 2 diabetes and 239 patients without diabetes, Dr. Huang said. The mean age was 51, and the mean body mass index was 34.7. The patients with diabetes were more likely to be older, to be women, and to have metabolic syndrome, NASH, and a higher fibrosis stage.

Notably, the median HbA1c among patients with diabetes was 6.8%, indicating a cohort with fairly well-controlled blood sugar. The median time between biopsies was 3.3 years.
 

Difference in progression, not regression

Overall, 151 participants (34%) experienced fibrosis progression, the primary study outcome. In a secondary outcome, 102 participants (23%) had fibrosis regression. The remaining 194 participants (43%) had no change in fibrosis stage. About 26% of patients with types 2 diabetes progressed to advanced fibrosis, as compared with 14.1% of patients without diabetes.

Among all those with fibrosis progression, the rate was 0.15 stages per year, with an average progression rate of one stage over 6.7 years. For patients with diabetes, the progression rate was significantly higher at 0.17 stages per year, compared with 0.13 stages per year among patients without diabetes, Dr. Huang said. That translated to an average progression of one stage over 5.9 years for patients with diabetes and 7.7 years for patients without diabetes.

In contrast, the regression rate was similar between those with or without diabetes at baseline, at –0.13 stages per year for those with diabetes versus –0.14 stages per year for those without diabetes. The similar outcome translated to an average regression of one stage over 7.7 years among those with diabetes and 7.1 years among those without diabetes.

Type 2 diabetes was an independent predictor of fibrosis progression in NAFLD, in both unadjusted and multivariable adjusted models, including baseline fibrosis stage, Dr. Huang said. In addition, patients with diabetes had a significantly higher cumulative incidence of fibrosis progression at 4 years (23% versus 19%), 8 years (59% versus 49%), and 12 years (93% versus 76%).

The research team didn’t find a significant difference in HbA1c as a predictor of fibrosis progression when using a cutoff of 7%.

“It is possible that poor glycemic control may accelerate fibrosis further, but we need studies to validate this,” Dr. Huang said. “These data have important implications for clinical practice and clinical trial design. Patients with NAFLD and diabetes may require more frequent monitoring for disease progression.”

The NASH Clinical Research Network consortium is sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Huang has served on an advisory board for Eisai. The other authors declared various research support and advisory roles with numerous pharmaceutical companies.

Among people with nonalcoholic fatty liver disease (NAFLD), the fibrosis progression rate was higher among those who also had diabetes, according to new findings presented at the annual meeting of the American Association for the Study of Liver Diseases.

NAFLD patients with type 2 diabetes progressed by one stage about every 6 years, compared with one stage about every 8 years among patients without diabetes, said Daniel Huang, MBBS, a visiting scholar at the University of California San Diego (UCSD) NAFLD Research Center and a transplant hepatologist at National University Hospital in Singapore.

“We now know that fibrosis stage is a major determinant of liver-related outcomes in NAFLD, as well as overall mortality,” he said. “Liver fibrosis progresses by approximately one stage every 7 years for individuals with NASH (nonalcoholic steatohepatitis).”

Recent UCSD data have indicated that about 14% of patients over age 50 with type 2 diabetes have NAFLD with advanced fibrosis, he noted. Previous studies have shown that diabetes is associated with higher rates of advanced fibrosis, cirrhosis, and hepatocellular carcinoma, but limited data exist around whether the fibrosis progression rate is higher among diabetics.
 

National study cohort

Dr. Huang and colleagues conducted a multicenter, multiethnic prospective cohort study within the NASH Clinical Research Network consortium to examine the fibrosis progression rate and the fibrosis regression rate among patients with or without diabetes. The study included adult participants at eight sites across the United States who had biopsy-confirmed NAFLD and available paired liver biopsies that were at least 1 year apart.

Clinical and laboratory data were obtained at enrollment and prospectively at 48-week intervals and recorded at the time of any liver biopsies. A central pathology committee conducted the liver histology assessment, and the entire pathology committee was blinded to clinical data and the sequence of liver biopsy. The fibrosis progression and regression rates were defined as the change in fibrosis stage over time between biopsies, measured in years.

The study comprised 447 adult participants with NAFLD: 208 patients with type 2 diabetes and 239 patients without diabetes, Dr. Huang said. The mean age was 51, and the mean body mass index was 34.7. The patients with diabetes were more likely to be older, to be women, and to have metabolic syndrome, NASH, and a higher fibrosis stage.

Notably, the median HbA1c among patients with diabetes was 6.8%, indicating a cohort with fairly well-controlled blood sugar. The median time between biopsies was 3.3 years.
 

Difference in progression, not regression

Overall, 151 participants (34%) experienced fibrosis progression, the primary study outcome. In a secondary outcome, 102 participants (23%) had fibrosis regression. The remaining 194 participants (43%) had no change in fibrosis stage. About 26% of patients with types 2 diabetes progressed to advanced fibrosis, as compared with 14.1% of patients without diabetes.

Among all those with fibrosis progression, the rate was 0.15 stages per year, with an average progression rate of one stage over 6.7 years. For patients with diabetes, the progression rate was significantly higher at 0.17 stages per year, compared with 0.13 stages per year among patients without diabetes, Dr. Huang said. That translated to an average progression of one stage over 5.9 years for patients with diabetes and 7.7 years for patients without diabetes.

In contrast, the regression rate was similar between those with or without diabetes at baseline, at –0.13 stages per year for those with diabetes versus –0.14 stages per year for those without diabetes. The similar outcome translated to an average regression of one stage over 7.7 years among those with diabetes and 7.1 years among those without diabetes.

Type 2 diabetes was an independent predictor of fibrosis progression in NAFLD, in both unadjusted and multivariable adjusted models, including baseline fibrosis stage, Dr. Huang said. In addition, patients with diabetes had a significantly higher cumulative incidence of fibrosis progression at 4 years (23% versus 19%), 8 years (59% versus 49%), and 12 years (93% versus 76%).

The research team didn’t find a significant difference in HbA1c as a predictor of fibrosis progression when using a cutoff of 7%.

“It is possible that poor glycemic control may accelerate fibrosis further, but we need studies to validate this,” Dr. Huang said. “These data have important implications for clinical practice and clinical trial design. Patients with NAFLD and diabetes may require more frequent monitoring for disease progression.”

The NASH Clinical Research Network consortium is sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Huang has served on an advisory board for Eisai. The other authors declared various research support and advisory roles with numerous pharmaceutical companies.

Among people with nonalcoholic fatty liver disease (NAFLD), the fibrosis progression rate was higher among those who also had diabetes, according to new findings presented at the annual meeting of the American Association for the Study of Liver Diseases.

NAFLD patients with type 2 diabetes progressed by one stage about every 6 years, compared with one stage about every 8 years among patients without diabetes, said Daniel Huang, MBBS, a visiting scholar at the University of California San Diego (UCSD) NAFLD Research Center and a transplant hepatologist at National University Hospital in Singapore.

“We now know that fibrosis stage is a major determinant of liver-related outcomes in NAFLD, as well as overall mortality,” he said. “Liver fibrosis progresses by approximately one stage every 7 years for individuals with NASH (nonalcoholic steatohepatitis).”

Recent UCSD data have indicated that about 14% of patients over age 50 with type 2 diabetes have NAFLD with advanced fibrosis, he noted. Previous studies have shown that diabetes is associated with higher rates of advanced fibrosis, cirrhosis, and hepatocellular carcinoma, but limited data exist around whether the fibrosis progression rate is higher among diabetics.
 

National study cohort

Dr. Huang and colleagues conducted a multicenter, multiethnic prospective cohort study within the NASH Clinical Research Network consortium to examine the fibrosis progression rate and the fibrosis regression rate among patients with or without diabetes. The study included adult participants at eight sites across the United States who had biopsy-confirmed NAFLD and available paired liver biopsies that were at least 1 year apart.

Clinical and laboratory data were obtained at enrollment and prospectively at 48-week intervals and recorded at the time of any liver biopsies. A central pathology committee conducted the liver histology assessment, and the entire pathology committee was blinded to clinical data and the sequence of liver biopsy. The fibrosis progression and regression rates were defined as the change in fibrosis stage over time between biopsies, measured in years.

The study comprised 447 adult participants with NAFLD: 208 patients with type 2 diabetes and 239 patients without diabetes, Dr. Huang said. The mean age was 51, and the mean body mass index was 34.7. The patients with diabetes were more likely to be older, to be women, and to have metabolic syndrome, NASH, and a higher fibrosis stage.

Notably, the median HbA1c among patients with diabetes was 6.8%, indicating a cohort with fairly well-controlled blood sugar. The median time between biopsies was 3.3 years.
 

Difference in progression, not regression

Overall, 151 participants (34%) experienced fibrosis progression, the primary study outcome. In a secondary outcome, 102 participants (23%) had fibrosis regression. The remaining 194 participants (43%) had no change in fibrosis stage. About 26% of patients with types 2 diabetes progressed to advanced fibrosis, as compared with 14.1% of patients without diabetes.

Among all those with fibrosis progression, the rate was 0.15 stages per year, with an average progression rate of one stage over 6.7 years. For patients with diabetes, the progression rate was significantly higher at 0.17 stages per year, compared with 0.13 stages per year among patients without diabetes, Dr. Huang said. That translated to an average progression of one stage over 5.9 years for patients with diabetes and 7.7 years for patients without diabetes.

In contrast, the regression rate was similar between those with or without diabetes at baseline, at –0.13 stages per year for those with diabetes versus –0.14 stages per year for those without diabetes. The similar outcome translated to an average regression of one stage over 7.7 years among those with diabetes and 7.1 years among those without diabetes.

Type 2 diabetes was an independent predictor of fibrosis progression in NAFLD, in both unadjusted and multivariable adjusted models, including baseline fibrosis stage, Dr. Huang said. In addition, patients with diabetes had a significantly higher cumulative incidence of fibrosis progression at 4 years (23% versus 19%), 8 years (59% versus 49%), and 12 years (93% versus 76%).

The research team didn’t find a significant difference in HbA1c as a predictor of fibrosis progression when using a cutoff of 7%.

“It is possible that poor glycemic control may accelerate fibrosis further, but we need studies to validate this,” Dr. Huang said. “These data have important implications for clinical practice and clinical trial design. Patients with NAFLD and diabetes may require more frequent monitoring for disease progression.”

The NASH Clinical Research Network consortium is sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Huang has served on an advisory board for Eisai. The other authors declared various research support and advisory roles with numerous pharmaceutical companies.

CHICAGO – None of six commercial dietary supplements widely promoted and taken for lowering LDL cholesterol did the job any better than placebo in a randomized trial of adults without cardiovascular disease but at increased cardiovascular risk.

In contrast, those who took the low dose of a high-potency statin in the eight-arm comparative study showed a significant 38% drop in LDL cholesterol levels over 28 days, a performance that blew away the six supplements containing fish oil, cinnamon, garlic, turmeric, plant sterols, or red yeast rice.

The supplements showed little or no effect on any measured lipid biomarkers, which also included total cholesterol and triglycerides, or C-reactive protein (CRP), which reflects systemic inflammation.

The findings undercut the widespread heart-health marketing claims for such supplements and could potentially restore faith in statins for the many patients looking for alternatives, researchers say.

“We all see patients that have their medication lists littered with dietary supplements,” observed Luke J. Laffin, MD, of the Cleveland Clinic Foundation. And it’s more than just heart patients who use them.

Almost $50 billion is spent on dietary supplements annually in the United States, and recent data suggest that more than three-fourths of the population use them, 18% of those based on specious heart-health claims, Dr. Laffin said in a Nov. 6 presentation at the American Heart Association scientific sessions.

The findings of the Supplements, Placebo, or Rosuvastatin Study (SPORT) and how they are framed for the public “are important for public health,” he said.

“As cardiologists, primary care doctors, and others, we really should use these results to have evidence-based discussions with patients” regarding the value of even low-dose statins and the supplements’ “lack of benefit,” said Dr. Laffin, lead author on the SPORT publication, which was published the same day in the Journal of the American College of Cardiology.

Patients assigned to low-dose rosuvastatin showed a mean 24.4% drop in total cholesterol levels over 28 days, the study’s primary endpoint. That differed from the placebo group and those for each supplement at P < .001.

They also averaged a 19.2% decrease in serum triglycerides, P < .05 for all group comparisons. None of the six supplements was significantly different from placebo for change in levels of either total cholesterol or triglycerides.

Nor were there significant differences in adverse events across the groups; there were no adverse changes in liver or kidney function tests or glucose levels; and there were no signs of musculoskeletal symptoms, the published report notes.
 

How to message the results

The SPORT trial is valuable for “addressing the void of data on supplements and cardiovascular health,” Chiadi E. Ndumele, MD, PhD, Johns Hopkins University, Baltimore, said as the invited discussant following Dr. Laffin’s presentation.

But they also send a reassuring message about statins, he noted. In a recent study of statin-nonadherent patients, 80% “were worried about statin side effects as the primary reason for not taking their statin, and 72% preferred using natural supplements instead of taking their prescription therapy,” Dr. Ndumele said. “The reason for this is clearly mistrust, misinformation, and a lack of evidence.”

The next step, he proposed, should be to get the study’s positive message about statins to the public, and especially patients “who are hesitant about statin use.” The current study “underscores the fact that using a low dose of a high-potency statin is associated with a very, very low risk of side effects.”

At a media briefing on SPORT, Amit Khera, MD, agreed the randomized trial provides some needed evidence that can be discussed with patients. “If someone’s coming to see me for cholesterol, we can say definitively now, at least there is data that these [supplements] don’t help your cholesterol and statins do.” Dr. Khera directs the preventive cardiology program at University of Texas Southwestern Medical Center, Dallas.

“I think for those who are there very specifically to lower their cholesterol, hopefully this will resonate,” he said.

“I personally didn’t see a lot of harms in using these supplements. But I also didn’t see any benefits,” Dr. Khera told this news organization.

“Now, if you’re taking them for other reasons, so be it. But if you need to lower your cholesterol for cardiovascular health reasons,” he said, “you need to know that they are minimally to not effective at all.”

But such supplements still “are not without harm,” Dr. Laffin proposed at the press conference. For example, they have potential for drug-drug interactions, “not only with cardiovascular medicines, but those taken for other reasons,” he said. “There are 90,000 supplements on the market in the United States today, and there are all kinds of potential safety issues associated with them.”

In patient discussions, Dr. Laffin said, “I do not think it’s good enough to say, you can waste your money [on supplements] as long as you’re taking your statin. These can actually be harmful in certain situations.”

SPORT, described as a single-center study, randomly assigned 199 participants from “throughout the Cleveland Clinic Health System in northeast Ohio” to one of the eight treatment groups. The investigators were blinded to treatment assignments, Dr. Laffin reported.
 

High adherence

Entry criteria included age 40 to 75 years with no history of cardiovascular disease, LDL-cholesterol from 70 to 189 mg/dL, and a 5%-20% 10-year risk of atherosclerotic cardiovascular disease by the pooled cohort equations. The predominantly White cohort averaged 64.4 years in age and 59% were women.

They were assigned to receive rosuvastatin 5 mg daily, placebo, or daily doses of supplements, with 25 patients per group, except the fish-oil group, which comprised 24 patients.

The daily supplement dosages were 2,400 mg for fish oil (Nature Made); 2,400 mg for cinnamon (NutriFlair), 5,000 mcg allicin for the garlic (Garlique), 4,500 mg for turmeric curcumin (BioSchwartz), 1,600 mg plant sterols (CholestOff Plus, Nature Made), and 2,400 mg red yeast rice (Arazo Nutrition).

Adherence to the assigned regimens was high, Dr. Laffin said, given that only four participants took less than 70% of their assigned doses.

Levels of LDL cholesterol in the statin group fell by 37.9% in 28 days, and by 35.2% relative to the placebo group (P < .001 for both differences), whereas any changes in LDL cholesterol among patients taking the most supplements were not significantly different from the placebo group. Of note, LDL cholesterol levels rose 7.8% (P = .01) compared with placebo among the group assigned to the garlic supplement.

Rosuvastatin had no apparent effect on HDL cholesterol levels, nor did most of the supplements; but such levels in patients taking the plant sterol supplement decreased by 7.1% (P = .02) compared to placebo and by 4% (P = .01) compared to the statin group.

None of the noncontrol groups, including those assigned to rosuvastatin, showed significant changes in high-sensitivity CRP levels compared with the placebo group. The lack of rosuvastatin effect on the inflammatory biomarker, the researchers speculated, is probably explained by the statins’ low dose as well as the limited size of the trial population.

There were two serious adverse events, including one deep venous thrombosis in the placebo group and a liver adenocarcinoma in a patient assigned to fish oil who “had not yet taken any of the study drug at the time of the serious adverse event,” the published report notes.
It remains open whether any of the assigned regimens could show different results over the long term, Dr. Laffin said. The SPORT trial’s 28-day duration, he said, “may not have fully captured the impact of supplements on lipid and inflammatory biomarkers.”

Nor is it known whether the supplements can potentially affect clinical outcomes. But “you could make an argument that it would be unethical” to randomize similar patients to a placebo-controlled, cardiovascular outcomes trial comparing the same six supplements and a statin.

Dr. Laffin has disclosed consulting or serving on a steering committee for Medtronic, Lilly, Mineralys Therapeutics, AstraZeneca, and Crispr Therapeutics; receiving research funding from AstraZeneca; and having ownership interest in LucidAct Health and Gordy Health. Dr. Ndumele and Dr. Khera have reported no relevant financial relationships.

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

CHICAGO – None of six commercial dietary supplements widely promoted and taken for lowering LDL cholesterol did the job any better than placebo in a randomized trial of adults without cardiovascular disease but at increased cardiovascular risk.

In contrast, those who took the low dose of a high-potency statin in the eight-arm comparative study showed a significant 38% drop in LDL cholesterol levels over 28 days, a performance that blew away the six supplements containing fish oil, cinnamon, garlic, turmeric, plant sterols, or red yeast rice.

The supplements showed little or no effect on any measured lipid biomarkers, which also included total cholesterol and triglycerides, or C-reactive protein (CRP), which reflects systemic inflammation.

The findings undercut the widespread heart-health marketing claims for such supplements and could potentially restore faith in statins for the many patients looking for alternatives, researchers say.

“We all see patients that have their medication lists littered with dietary supplements,” observed Luke J. Laffin, MD, of the Cleveland Clinic Foundation. And it’s more than just heart patients who use them.

Almost $50 billion is spent on dietary supplements annually in the United States, and recent data suggest that more than three-fourths of the population use them, 18% of those based on specious heart-health claims, Dr. Laffin said in a Nov. 6 presentation at the American Heart Association scientific sessions.

The findings of the Supplements, Placebo, or Rosuvastatin Study (SPORT) and how they are framed for the public “are important for public health,” he said.

“As cardiologists, primary care doctors, and others, we really should use these results to have evidence-based discussions with patients” regarding the value of even low-dose statins and the supplements’ “lack of benefit,” said Dr. Laffin, lead author on the SPORT publication, which was published the same day in the Journal of the American College of Cardiology.

Patients assigned to low-dose rosuvastatin showed a mean 24.4% drop in total cholesterol levels over 28 days, the study’s primary endpoint. That differed from the placebo group and those for each supplement at P < .001.

They also averaged a 19.2% decrease in serum triglycerides, P < .05 for all group comparisons. None of the six supplements was significantly different from placebo for change in levels of either total cholesterol or triglycerides.

Nor were there significant differences in adverse events across the groups; there were no adverse changes in liver or kidney function tests or glucose levels; and there were no signs of musculoskeletal symptoms, the published report notes.
 

How to message the results

The SPORT trial is valuable for “addressing the void of data on supplements and cardiovascular health,” Chiadi E. Ndumele, MD, PhD, Johns Hopkins University, Baltimore, said as the invited discussant following Dr. Laffin’s presentation.

But they also send a reassuring message about statins, he noted. In a recent study of statin-nonadherent patients, 80% “were worried about statin side effects as the primary reason for not taking their statin, and 72% preferred using natural supplements instead of taking their prescription therapy,” Dr. Ndumele said. “The reason for this is clearly mistrust, misinformation, and a lack of evidence.”

The next step, he proposed, should be to get the study’s positive message about statins to the public, and especially patients “who are hesitant about statin use.” The current study “underscores the fact that using a low dose of a high-potency statin is associated with a very, very low risk of side effects.”

At a media briefing on SPORT, Amit Khera, MD, agreed the randomized trial provides some needed evidence that can be discussed with patients. “If someone’s coming to see me for cholesterol, we can say definitively now, at least there is data that these [supplements] don’t help your cholesterol and statins do.” Dr. Khera directs the preventive cardiology program at University of Texas Southwestern Medical Center, Dallas.

“I think for those who are there very specifically to lower their cholesterol, hopefully this will resonate,” he said.

“I personally didn’t see a lot of harms in using these supplements. But I also didn’t see any benefits,” Dr. Khera told this news organization.

“Now, if you’re taking them for other reasons, so be it. But if you need to lower your cholesterol for cardiovascular health reasons,” he said, “you need to know that they are minimally to not effective at all.”

But such supplements still “are not without harm,” Dr. Laffin proposed at the press conference. For example, they have potential for drug-drug interactions, “not only with cardiovascular medicines, but those taken for other reasons,” he said. “There are 90,000 supplements on the market in the United States today, and there are all kinds of potential safety issues associated with them.”

In patient discussions, Dr. Laffin said, “I do not think it’s good enough to say, you can waste your money [on supplements] as long as you’re taking your statin. These can actually be harmful in certain situations.”

SPORT, described as a single-center study, randomly assigned 199 participants from “throughout the Cleveland Clinic Health System in northeast Ohio” to one of the eight treatment groups. The investigators were blinded to treatment assignments, Dr. Laffin reported.
 

High adherence

Entry criteria included age 40 to 75 years with no history of cardiovascular disease, LDL-cholesterol from 70 to 189 mg/dL, and a 5%-20% 10-year risk of atherosclerotic cardiovascular disease by the pooled cohort equations. The predominantly White cohort averaged 64.4 years in age and 59% were women.

They were assigned to receive rosuvastatin 5 mg daily, placebo, or daily doses of supplements, with 25 patients per group, except the fish-oil group, which comprised 24 patients.

The daily supplement dosages were 2,400 mg for fish oil (Nature Made); 2,400 mg for cinnamon (NutriFlair), 5,000 mcg allicin for the garlic (Garlique), 4,500 mg for turmeric curcumin (BioSchwartz), 1,600 mg plant sterols (CholestOff Plus, Nature Made), and 2,400 mg red yeast rice (Arazo Nutrition).

Adherence to the assigned regimens was high, Dr. Laffin said, given that only four participants took less than 70% of their assigned doses.

Levels of LDL cholesterol in the statin group fell by 37.9% in 28 days, and by 35.2% relative to the placebo group (P < .001 for both differences), whereas any changes in LDL cholesterol among patients taking the most supplements were not significantly different from the placebo group. Of note, LDL cholesterol levels rose 7.8% (P = .01) compared with placebo among the group assigned to the garlic supplement.

Rosuvastatin had no apparent effect on HDL cholesterol levels, nor did most of the supplements; but such levels in patients taking the plant sterol supplement decreased by 7.1% (P = .02) compared to placebo and by 4% (P = .01) compared to the statin group.

None of the noncontrol groups, including those assigned to rosuvastatin, showed significant changes in high-sensitivity CRP levels compared with the placebo group. The lack of rosuvastatin effect on the inflammatory biomarker, the researchers speculated, is probably explained by the statins’ low dose as well as the limited size of the trial population.

There were two serious adverse events, including one deep venous thrombosis in the placebo group and a liver adenocarcinoma in a patient assigned to fish oil who “had not yet taken any of the study drug at the time of the serious adverse event,” the published report notes.
It remains open whether any of the assigned regimens could show different results over the long term, Dr. Laffin said. The SPORT trial’s 28-day duration, he said, “may not have fully captured the impact of supplements on lipid and inflammatory biomarkers.”

Nor is it known whether the supplements can potentially affect clinical outcomes. But “you could make an argument that it would be unethical” to randomize similar patients to a placebo-controlled, cardiovascular outcomes trial comparing the same six supplements and a statin.

Dr. Laffin has disclosed consulting or serving on a steering committee for Medtronic, Lilly, Mineralys Therapeutics, AstraZeneca, and Crispr Therapeutics; receiving research funding from AstraZeneca; and having ownership interest in LucidAct Health and Gordy Health. Dr. Ndumele and Dr. Khera have reported no relevant financial relationships.

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

CHICAGO – None of six commercial dietary supplements widely promoted and taken for lowering LDL cholesterol did the job any better than placebo in a randomized trial of adults without cardiovascular disease but at increased cardiovascular risk.

In contrast, those who took the low dose of a high-potency statin in the eight-arm comparative study showed a significant 38% drop in LDL cholesterol levels over 28 days, a performance that blew away the six supplements containing fish oil, cinnamon, garlic, turmeric, plant sterols, or red yeast rice.

The supplements showed little or no effect on any measured lipid biomarkers, which also included total cholesterol and triglycerides, or C-reactive protein (CRP), which reflects systemic inflammation.

The findings undercut the widespread heart-health marketing claims for such supplements and could potentially restore faith in statins for the many patients looking for alternatives, researchers say.

“We all see patients that have their medication lists littered with dietary supplements,” observed Luke J. Laffin, MD, of the Cleveland Clinic Foundation. And it’s more than just heart patients who use them.

Almost $50 billion is spent on dietary supplements annually in the United States, and recent data suggest that more than three-fourths of the population use them, 18% of those based on specious heart-health claims, Dr. Laffin said in a Nov. 6 presentation at the American Heart Association scientific sessions.

The findings of the Supplements, Placebo, or Rosuvastatin Study (SPORT) and how they are framed for the public “are important for public health,” he said.

“As cardiologists, primary care doctors, and others, we really should use these results to have evidence-based discussions with patients” regarding the value of even low-dose statins and the supplements’ “lack of benefit,” said Dr. Laffin, lead author on the SPORT publication, which was published the same day in the Journal of the American College of Cardiology.

Patients assigned to low-dose rosuvastatin showed a mean 24.4% drop in total cholesterol levels over 28 days, the study’s primary endpoint. That differed from the placebo group and those for each supplement at P < .001.

They also averaged a 19.2% decrease in serum triglycerides, P < .05 for all group comparisons. None of the six supplements was significantly different from placebo for change in levels of either total cholesterol or triglycerides.

Nor were there significant differences in adverse events across the groups; there were no adverse changes in liver or kidney function tests or glucose levels; and there were no signs of musculoskeletal symptoms, the published report notes.
 

How to message the results

The SPORT trial is valuable for “addressing the void of data on supplements and cardiovascular health,” Chiadi E. Ndumele, MD, PhD, Johns Hopkins University, Baltimore, said as the invited discussant following Dr. Laffin’s presentation.

But they also send a reassuring message about statins, he noted. In a recent study of statin-nonadherent patients, 80% “were worried about statin side effects as the primary reason for not taking their statin, and 72% preferred using natural supplements instead of taking their prescription therapy,” Dr. Ndumele said. “The reason for this is clearly mistrust, misinformation, and a lack of evidence.”

The next step, he proposed, should be to get the study’s positive message about statins to the public, and especially patients “who are hesitant about statin use.” The current study “underscores the fact that using a low dose of a high-potency statin is associated with a very, very low risk of side effects.”

At a media briefing on SPORT, Amit Khera, MD, agreed the randomized trial provides some needed evidence that can be discussed with patients. “If someone’s coming to see me for cholesterol, we can say definitively now, at least there is data that these [supplements] don’t help your cholesterol and statins do.” Dr. Khera directs the preventive cardiology program at University of Texas Southwestern Medical Center, Dallas.

“I think for those who are there very specifically to lower their cholesterol, hopefully this will resonate,” he said.

“I personally didn’t see a lot of harms in using these supplements. But I also didn’t see any benefits,” Dr. Khera told this news organization.

“Now, if you’re taking them for other reasons, so be it. But if you need to lower your cholesterol for cardiovascular health reasons,” he said, “you need to know that they are minimally to not effective at all.”

But such supplements still “are not without harm,” Dr. Laffin proposed at the press conference. For example, they have potential for drug-drug interactions, “not only with cardiovascular medicines, but those taken for other reasons,” he said. “There are 90,000 supplements on the market in the United States today, and there are all kinds of potential safety issues associated with them.”

In patient discussions, Dr. Laffin said, “I do not think it’s good enough to say, you can waste your money [on supplements] as long as you’re taking your statin. These can actually be harmful in certain situations.”

SPORT, described as a single-center study, randomly assigned 199 participants from “throughout the Cleveland Clinic Health System in northeast Ohio” to one of the eight treatment groups. The investigators were blinded to treatment assignments, Dr. Laffin reported.
 

High adherence

Entry criteria included age 40 to 75 years with no history of cardiovascular disease, LDL-cholesterol from 70 to 189 mg/dL, and a 5%-20% 10-year risk of atherosclerotic cardiovascular disease by the pooled cohort equations. The predominantly White cohort averaged 64.4 years in age and 59% were women.

They were assigned to receive rosuvastatin 5 mg daily, placebo, or daily doses of supplements, with 25 patients per group, except the fish-oil group, which comprised 24 patients.

The daily supplement dosages were 2,400 mg for fish oil (Nature Made); 2,400 mg for cinnamon (NutriFlair), 5,000 mcg allicin for the garlic (Garlique), 4,500 mg for turmeric curcumin (BioSchwartz), 1,600 mg plant sterols (CholestOff Plus, Nature Made), and 2,400 mg red yeast rice (Arazo Nutrition).

Adherence to the assigned regimens was high, Dr. Laffin said, given that only four participants took less than 70% of their assigned doses.

Levels of LDL cholesterol in the statin group fell by 37.9% in 28 days, and by 35.2% relative to the placebo group (P < .001 for both differences), whereas any changes in LDL cholesterol among patients taking the most supplements were not significantly different from the placebo group. Of note, LDL cholesterol levels rose 7.8% (P = .01) compared with placebo among the group assigned to the garlic supplement.

Rosuvastatin had no apparent effect on HDL cholesterol levels, nor did most of the supplements; but such levels in patients taking the plant sterol supplement decreased by 7.1% (P = .02) compared to placebo and by 4% (P = .01) compared to the statin group.

None of the noncontrol groups, including those assigned to rosuvastatin, showed significant changes in high-sensitivity CRP levels compared with the placebo group. The lack of rosuvastatin effect on the inflammatory biomarker, the researchers speculated, is probably explained by the statins’ low dose as well as the limited size of the trial population.

There were two serious adverse events, including one deep venous thrombosis in the placebo group and a liver adenocarcinoma in a patient assigned to fish oil who “had not yet taken any of the study drug at the time of the serious adverse event,” the published report notes.
It remains open whether any of the assigned regimens could show different results over the long term, Dr. Laffin said. The SPORT trial’s 28-day duration, he said, “may not have fully captured the impact of supplements on lipid and inflammatory biomarkers.”

Nor is it known whether the supplements can potentially affect clinical outcomes. But “you could make an argument that it would be unethical” to randomize similar patients to a placebo-controlled, cardiovascular outcomes trial comparing the same six supplements and a statin.

Dr. Laffin has disclosed consulting or serving on a steering committee for Medtronic, Lilly, Mineralys Therapeutics, AstraZeneca, and Crispr Therapeutics; receiving research funding from AstraZeneca; and having ownership interest in LucidAct Health and Gordy Health. Dr. Ndumele and Dr. Khera have reported no relevant financial relationships.

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