Federal Practitioner

Nearly 2 years after a whistleblower alleged that the University of Pittsburgh Medical Center (UPMC) and its head of cardiothoracic surgery participated in billing fraud and dangerous operating room practices, the case has ended in an $8.5 million settlement, the Department of Justice (DOJ) announced.

The lawsuit alleges that James L. Luketich, MD, the longtime chair of the school’s cardiothoracic surgery department, regularly performed up to three complex surgical procedures simultaneously, moving among multiple operating rooms and attending to matters other than patient care. The investigation began after Jonathan D’Cunha, MD, a former UPMC surgeon, raised concerns about his colleague’s surgical scheduling and billing practices.

Dr. Luketich’s overbooking of procedures led to patients enduring hours of medically unnecessary anesthesia time and risking surgical complications, according to court documents.

In addition, the complaint states that these practices violated the False Claims Act, which prohibits “teaching physicians” like Dr. Luketich from billing Medicare and other government health plans for “concurrent surgeries” – regulations federal authorities say UPMC leadership were aware of and the University of Pittsburgh Physicians (UPP), also named in the suit, permitted Dr. Luketich to skirt.

The whistleblower provision of the False Claims Act allows private parties to file an action on behalf of the United States and receive a portion of the recovery to help deter health care fraud, says the DOJ.

The defendants previously asked the court to dismiss the case, but a judge denied the request in June 2022.

Paul Wood, vice president and chief communications officer for UPMC, told this news organization that the lawsuit pertained to Dr. Luketich’s “most complicated, team-based surgical procedures.”

“At issue was compliance with the Centers for Medicare & Medicaid Services’ (CMS’s) Teaching Physician Regulation and related billing guidance as well as with UPMC’s internal surgical policies,” he said.

“While UPMC continues to believe Dr. Luketich’s surgical practice complies with CMS requirements, it has agreed to [the settlement] to avoid the distraction and expense of further litigation,” said Mr. Wood, adding that all parties agree that UPMC can seek clarity from CMS regarding future billing of these surgeries.

Efrem Grail, JD, Dr. Luketich’s attorney, said in an interview that he and Dr. Luketich are pleased that the settlement puts an end to the case and that he hopes the United States will issue “authoritative guidance” on billing regulations for teaching physicians, something medical schools and hospitals have sought for years.

Dr. Luketich, UPMC, and UPP face more legal challenges from a separate medical malpractice lawsuit. In March 2018, Bernadette Fedorka underwent a lung transplant at UPMC. Although Dr. Luketich did not perform the surgery, Ms. Fedorka alleges that his poor leadership caused understaffing of the lung transplant program and contributed to surgical complications, including a 4-inch piece of wire left in her neck.

Ms. Fedorka claims that suboxone impaired Dr. Luketich’s decision-making. He began taking the drug in 2008 to manage the pain from a slipped disc injury after a history of prescription drug abuse. Both UPMC and Dr. Luketich have denied the validity of Ms. Fedorka’s claims.

The malpractice suit centers on a recording of a conversation between Dr. Luketich and David Wilson, MD, who prescribed the suboxone and treated the surgeon’s opioid use disorder for several years. Dr. Luketich has accused former colleagues, Dr. D’Cunha and Lara Schaheen, MD, of illegally recording the private conversation that discussed Dr. Luketich’s suboxone prescription – something both physicians deny.

For the billing fraud case, Dr. Luketich has agreed to complete a corrective action plan and submit to a third-party audit of his Medicare billings for 1 year.

“This is an important settlement and a just conclusion to the United States’ investigation into Dr. Luketich’s surgical and billing practices and UPMC and UPP’s acceptance of those practices,” Acting U.S. Attorney Troy Rivetti said in a statement that, “no medical provider – however renowned – is excepted from scrutiny or above the law.”

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

Nearly 2 years after a whistleblower alleged that the University of Pittsburgh Medical Center (UPMC) and its head of cardiothoracic surgery participated in billing fraud and dangerous operating room practices, the case has ended in an $8.5 million settlement, the Department of Justice (DOJ) announced.

The lawsuit alleges that James L. Luketich, MD, the longtime chair of the school’s cardiothoracic surgery department, regularly performed up to three complex surgical procedures simultaneously, moving among multiple operating rooms and attending to matters other than patient care. The investigation began after Jonathan D’Cunha, MD, a former UPMC surgeon, raised concerns about his colleague’s surgical scheduling and billing practices.

Dr. Luketich’s overbooking of procedures led to patients enduring hours of medically unnecessary anesthesia time and risking surgical complications, according to court documents.

In addition, the complaint states that these practices violated the False Claims Act, which prohibits “teaching physicians” like Dr. Luketich from billing Medicare and other government health plans for “concurrent surgeries” – regulations federal authorities say UPMC leadership were aware of and the University of Pittsburgh Physicians (UPP), also named in the suit, permitted Dr. Luketich to skirt.

The whistleblower provision of the False Claims Act allows private parties to file an action on behalf of the United States and receive a portion of the recovery to help deter health care fraud, says the DOJ.

The defendants previously asked the court to dismiss the case, but a judge denied the request in June 2022.

Paul Wood, vice president and chief communications officer for UPMC, told this news organization that the lawsuit pertained to Dr. Luketich’s “most complicated, team-based surgical procedures.”

“At issue was compliance with the Centers for Medicare & Medicaid Services’ (CMS’s) Teaching Physician Regulation and related billing guidance as well as with UPMC’s internal surgical policies,” he said.

“While UPMC continues to believe Dr. Luketich’s surgical practice complies with CMS requirements, it has agreed to [the settlement] to avoid the distraction and expense of further litigation,” said Mr. Wood, adding that all parties agree that UPMC can seek clarity from CMS regarding future billing of these surgeries.

Efrem Grail, JD, Dr. Luketich’s attorney, said in an interview that he and Dr. Luketich are pleased that the settlement puts an end to the case and that he hopes the United States will issue “authoritative guidance” on billing regulations for teaching physicians, something medical schools and hospitals have sought for years.

Dr. Luketich, UPMC, and UPP face more legal challenges from a separate medical malpractice lawsuit. In March 2018, Bernadette Fedorka underwent a lung transplant at UPMC. Although Dr. Luketich did not perform the surgery, Ms. Fedorka alleges that his poor leadership caused understaffing of the lung transplant program and contributed to surgical complications, including a 4-inch piece of wire left in her neck.

Ms. Fedorka claims that suboxone impaired Dr. Luketich’s decision-making. He began taking the drug in 2008 to manage the pain from a slipped disc injury after a history of prescription drug abuse. Both UPMC and Dr. Luketich have denied the validity of Ms. Fedorka’s claims.

The malpractice suit centers on a recording of a conversation between Dr. Luketich and David Wilson, MD, who prescribed the suboxone and treated the surgeon’s opioid use disorder for several years. Dr. Luketich has accused former colleagues, Dr. D’Cunha and Lara Schaheen, MD, of illegally recording the private conversation that discussed Dr. Luketich’s suboxone prescription – something both physicians deny.

For the billing fraud case, Dr. Luketich has agreed to complete a corrective action plan and submit to a third-party audit of his Medicare billings for 1 year.

“This is an important settlement and a just conclusion to the United States’ investigation into Dr. Luketich’s surgical and billing practices and UPMC and UPP’s acceptance of those practices,” Acting U.S. Attorney Troy Rivetti said in a statement that, “no medical provider – however renowned – is excepted from scrutiny or above the law.”

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

Nearly 2 years after a whistleblower alleged that the University of Pittsburgh Medical Center (UPMC) and its head of cardiothoracic surgery participated in billing fraud and dangerous operating room practices, the case has ended in an $8.5 million settlement, the Department of Justice (DOJ) announced.

The lawsuit alleges that James L. Luketich, MD, the longtime chair of the school’s cardiothoracic surgery department, regularly performed up to three complex surgical procedures simultaneously, moving among multiple operating rooms and attending to matters other than patient care. The investigation began after Jonathan D’Cunha, MD, a former UPMC surgeon, raised concerns about his colleague’s surgical scheduling and billing practices.

Dr. Luketich’s overbooking of procedures led to patients enduring hours of medically unnecessary anesthesia time and risking surgical complications, according to court documents.

In addition, the complaint states that these practices violated the False Claims Act, which prohibits “teaching physicians” like Dr. Luketich from billing Medicare and other government health plans for “concurrent surgeries” – regulations federal authorities say UPMC leadership were aware of and the University of Pittsburgh Physicians (UPP), also named in the suit, permitted Dr. Luketich to skirt.

The whistleblower provision of the False Claims Act allows private parties to file an action on behalf of the United States and receive a portion of the recovery to help deter health care fraud, says the DOJ.

The defendants previously asked the court to dismiss the case, but a judge denied the request in June 2022.

Paul Wood, vice president and chief communications officer for UPMC, told this news organization that the lawsuit pertained to Dr. Luketich’s “most complicated, team-based surgical procedures.”

“At issue was compliance with the Centers for Medicare & Medicaid Services’ (CMS’s) Teaching Physician Regulation and related billing guidance as well as with UPMC’s internal surgical policies,” he said.

“While UPMC continues to believe Dr. Luketich’s surgical practice complies with CMS requirements, it has agreed to [the settlement] to avoid the distraction and expense of further litigation,” said Mr. Wood, adding that all parties agree that UPMC can seek clarity from CMS regarding future billing of these surgeries.

Efrem Grail, JD, Dr. Luketich’s attorney, said in an interview that he and Dr. Luketich are pleased that the settlement puts an end to the case and that he hopes the United States will issue “authoritative guidance” on billing regulations for teaching physicians, something medical schools and hospitals have sought for years.

Dr. Luketich, UPMC, and UPP face more legal challenges from a separate medical malpractice lawsuit. In March 2018, Bernadette Fedorka underwent a lung transplant at UPMC. Although Dr. Luketich did not perform the surgery, Ms. Fedorka alleges that his poor leadership caused understaffing of the lung transplant program and contributed to surgical complications, including a 4-inch piece of wire left in her neck.

Ms. Fedorka claims that suboxone impaired Dr. Luketich’s decision-making. He began taking the drug in 2008 to manage the pain from a slipped disc injury after a history of prescription drug abuse. Both UPMC and Dr. Luketich have denied the validity of Ms. Fedorka’s claims.

The malpractice suit centers on a recording of a conversation between Dr. Luketich and David Wilson, MD, who prescribed the suboxone and treated the surgeon’s opioid use disorder for several years. Dr. Luketich has accused former colleagues, Dr. D’Cunha and Lara Schaheen, MD, of illegally recording the private conversation that discussed Dr. Luketich’s suboxone prescription – something both physicians deny.

For the billing fraud case, Dr. Luketich has agreed to complete a corrective action plan and submit to a third-party audit of his Medicare billings for 1 year.

“This is an important settlement and a just conclusion to the United States’ investigation into Dr. Luketich’s surgical and billing practices and UPMC and UPP’s acceptance of those practices,” Acting U.S. Attorney Troy Rivetti said in a statement that, “no medical provider – however renowned – is excepted from scrutiny or above the law.”

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

Sitting for more than 8 hours per day increases the chances of becoming overweight or obese, unlike sitting for only 4 hours per day, according to a recent Latin American study published in BMC Public Health.

These data come from almost 8,000 people aged 20-65 years (half of whom are women) who participated in the Latin American Study on Nutrition and Health (ELANS). The cross-sectional survey included representative samples from urban populations in Argentina, Brazil, Chile, Colombia, Costa Rica, Ecuador, Peru, and Venezuela. The average time spent sitting was 420 min/d. Ecuador had the lowest time (300 min/day), and Argentina and Peru had the highest (480 min/day).

No amount of sitting time has been associated with a greater health risk, but the World Health Organization recommends that sitting time be minimal.

“We used to believe that any intense physical exercise could compensate for a sedentary life. But now we know that a sedentary lifestyle in general and sitting time in particular have a direct effect and are an independent risk factor for chronic diseases,” said study author Irina Kovalskys, PhD, a pediatric specialist in nutrition and a professor of nutrition at the Catholic University of Argentina, Buenos Aires, and a principal investigator of ELANS.

Dr. Kovalskys stated that the 420-min average sitting time is worrying in a population such as the one studied, in which 60% of adults are obese and there are high rates of cardiometabolic risk factors. She affirmed that it is important to raise awareness among the population and focus on adolescents.

Felipe Lobelo, PhD, is a Colombian physician, an associate professor of global health at Emory University and director of epidemiology at Kaiser Permanente Georgia, both in Atlanta. He did not participate in this study but promotes the concept of exercise in medicine. The activity of the patient must be included in a clinical setting, and improving the level of physical activity can have a positive impact on health prognosis, he said.

“To make public health recommendations or even advise patients, a cutoff point is needed. Guidelines recommend 150 minutes per week of moderate to vigorous physical activity, and some countries have started to indicate that we should be concerned about people’s sitting time. There is still no equivalent to the 150 minutes, therefore, these studies are important, especially in the Latin American population,” said Dr. Lobelo.

He explained that the concept of an increased risk of death or chronic disease because of a lack of physical activity arose in the past 50 years, but only in the past 2 decades have we started thinking about sitting time.

“Spending more than 8 hours sitting per day clearly causes a much higher risk of chronic diseases, including obesity and diabetes. It may be a continuous and progressive association, and the point at which this increase becomes exponential is clearly between 6 and 8 hours of sitting time,” Dr. Lobelo added.

The authors expected to find a linear association with risk for being overweight or obese after 4 hours, but they did not find one. “This study has limitations. Among them was that other indicators were not considered, such as health indicators. Collaborations are starting with other research groups, and other studies are being designed,” said study author Gerson Ferrari, PhD, an associate professor at Santiago de Chile University.
 

Comparing indicators

The Latin American study tried to establish a sitting cutoff time after which the risk of becoming overweight or obese increases. It used three indicators of excess weight: body mass index (BMI), waist circumference, and neck circumference.

Sitting for more than 8 hours increased the chances of excess weight by 10% when measured by BMI and by 13% when neck circumference was used.

Dr. Ferrari stated that the result obtained measuring BMI is the one that should be considered, because it is used in public policy. Neck circumference is a more recent measurement of detection and it is less studied, but it is a valid indicator, with good sensitivity and advantages over others, such as ease of measurement and lack of variation over time.

According to the results of this study, measuring neck circumference may be the most sensitive method of the three. Neck circumference was proportionally greater in people who sat for at least 4, at least 6, and at least 8 hours/day than in those who sat for less than 4, less than 6, and less than 8 hours/day. This relationship was not observed with the other indicators.
 

Broaching the topic

“What is important is uninterrupted sitting time. The recommendation is to break up those sitting times with active periods. Health professionals have already incorporated the concept of moderate to vigorous physical exercise, but nonintense activities are sufficient to reduce sitting time. Yoga may not be vigorous, but it is valuable at reducing sitting time,” said Dr. Kovalskys.

Dr. Ferrari recommended giving patients concrete messages so that they spend as little time possible sitting. “It is better to stand on the bus or the subway even when there is a place to sit. Are you going to talk on the phone? It is better to do it while walking or at least standing instead of sitting.”

A recent literature review conducted by investigators of the University of Birmingham (England) studied the possible molecular and physiologic mechanisms of inactivity time, health consequences, and protection strategies. It offers an evaluation of interventions that can compensate for the immediate negative consequences of inactivity.
 

Physical activity

Some studies suggest that more than 60 min/day of moderate-intensity exercise or more than 150 min/week of moderate to vigorous exercise may be effective at mitigating the increased risk for mortality associated with sitting time, but reduced intensity may not be enough.

Active pauses

Interrupting sitting every 30-60 min to walk or cycle (2-10 min), performing 3 minutes of simple resistance activities every 30 minutes, such as calf or knee lifts, performing intermittent leg movements (1 minute of activity for every 4 minutes of inactivity during a 3-hour protocol session), or pausing to climb stairs (5 minutes every hour) may be beneficial for vascular health. However, not all studies have demonstrated these positive effects, therefore, some populations may need exercise of greater intensity or duration to counteract the negative vascular effects of acute inactivity periods.

Standing workstations

Standing workstations are effective at reducing sitting time in offices but may be ineffective at reducing vascular alterations related to sitting time. Although some experimental studies indicate vascular benefits, epidemiologic studies suggest that long periods of standing can be harmful to vascular health, especially for venous diseases. Recommendations for use should be accompanied by specific regimens on the frequency and duration of the position to attain the maximum benefits and minimize other vascular complications.

One problem that Dr. Lobelo noted is that some doctors ask their patients how active they are, but they do so in a nonstandardized manner. This observation led him to publish, together with the American Heart Association, an article on the importance for health systems of considering physical activity as a vital sign and including it in records in a standardized manner.

He said that “one advantage of having physical activity as a vital sign in patient medical records is that it allows us to identify individuals who are at greater risk.”

Kaiser Permanente asks the following questions: how many minutes of physical activity do you perform regularly per week, and what is the average intensity of that activity? Patients can be classified into the following three groups: those who follow the recommendations, those with almost no activity, and those who perform some physical activity but do not meet the recommended 150 min/week of moderate to vigorous activity.

Recording sitting time is more difficult. Dr. Lobelo indicated that “it is easier for a person to remember how much time they spent running than how long they were sitting.” Regarding the use of technology, he commented that most watches provide a good estimate. Without technology, it can be estimated by asking how much time is spent in the car, on the bus, or in front of the computer or television and then adding up these times.

Dr. Lobelo emphasized that the two behaviors, lack of physical activity and excessive sitting time, have independent associations with health outcomes. But if both are combined, the risk of obesity, diabetes, and cardiovascular diseases is not just added but rather is multiplied. These behaviors contribute to the epidemic of obesity and diabetes, since most people do not follow either of the two recommendations.

“Studies show that of the two behaviors, the more negative for health would be not following the physical activity recommendations,” said Dr. Lobelo. “If the recommendation of 150 min/week of moderate to vigorous physical activity is followed, the associated risk of sitting too much declines by 80%-90%. Additionally, we can prevent, help to manage, and decrease the risk of complications in more than 100 diseases, including infections. During the pandemic, it was observed that more active people had a lower risk of dying or of being hospitalized due to COVID-19 than less active people, independently of other factors, such as hypertension, diabetes, and obesity.”

Moreover, Dr. Lobelo believes in “practicing what you preach” and advocates that doctors become healthy models.

Dr. Lobelo, Dr. Ferrari, and Dr. Kovalskys disclosed no relevant financial relationships.

This article was translated from the Medscape Spanish edition. A version appeared on Medscape.com.

Sitting for more than 8 hours per day increases the chances of becoming overweight or obese, unlike sitting for only 4 hours per day, according to a recent Latin American study published in BMC Public Health.

These data come from almost 8,000 people aged 20-65 years (half of whom are women) who participated in the Latin American Study on Nutrition and Health (ELANS). The cross-sectional survey included representative samples from urban populations in Argentina, Brazil, Chile, Colombia, Costa Rica, Ecuador, Peru, and Venezuela. The average time spent sitting was 420 min/d. Ecuador had the lowest time (300 min/day), and Argentina and Peru had the highest (480 min/day).

No amount of sitting time has been associated with a greater health risk, but the World Health Organization recommends that sitting time be minimal.

“We used to believe that any intense physical exercise could compensate for a sedentary life. But now we know that a sedentary lifestyle in general and sitting time in particular have a direct effect and are an independent risk factor for chronic diseases,” said study author Irina Kovalskys, PhD, a pediatric specialist in nutrition and a professor of nutrition at the Catholic University of Argentina, Buenos Aires, and a principal investigator of ELANS.

Dr. Kovalskys stated that the 420-min average sitting time is worrying in a population such as the one studied, in which 60% of adults are obese and there are high rates of cardiometabolic risk factors. She affirmed that it is important to raise awareness among the population and focus on adolescents.

Felipe Lobelo, PhD, is a Colombian physician, an associate professor of global health at Emory University and director of epidemiology at Kaiser Permanente Georgia, both in Atlanta. He did not participate in this study but promotes the concept of exercise in medicine. The activity of the patient must be included in a clinical setting, and improving the level of physical activity can have a positive impact on health prognosis, he said.

“To make public health recommendations or even advise patients, a cutoff point is needed. Guidelines recommend 150 minutes per week of moderate to vigorous physical activity, and some countries have started to indicate that we should be concerned about people’s sitting time. There is still no equivalent to the 150 minutes, therefore, these studies are important, especially in the Latin American population,” said Dr. Lobelo.

He explained that the concept of an increased risk of death or chronic disease because of a lack of physical activity arose in the past 50 years, but only in the past 2 decades have we started thinking about sitting time.

“Spending more than 8 hours sitting per day clearly causes a much higher risk of chronic diseases, including obesity and diabetes. It may be a continuous and progressive association, and the point at which this increase becomes exponential is clearly between 6 and 8 hours of sitting time,” Dr. Lobelo added.

The authors expected to find a linear association with risk for being overweight or obese after 4 hours, but they did not find one. “This study has limitations. Among them was that other indicators were not considered, such as health indicators. Collaborations are starting with other research groups, and other studies are being designed,” said study author Gerson Ferrari, PhD, an associate professor at Santiago de Chile University.
 

Comparing indicators

The Latin American study tried to establish a sitting cutoff time after which the risk of becoming overweight or obese increases. It used three indicators of excess weight: body mass index (BMI), waist circumference, and neck circumference.

Sitting for more than 8 hours increased the chances of excess weight by 10% when measured by BMI and by 13% when neck circumference was used.

Dr. Ferrari stated that the result obtained measuring BMI is the one that should be considered, because it is used in public policy. Neck circumference is a more recent measurement of detection and it is less studied, but it is a valid indicator, with good sensitivity and advantages over others, such as ease of measurement and lack of variation over time.

According to the results of this study, measuring neck circumference may be the most sensitive method of the three. Neck circumference was proportionally greater in people who sat for at least 4, at least 6, and at least 8 hours/day than in those who sat for less than 4, less than 6, and less than 8 hours/day. This relationship was not observed with the other indicators.
 

Broaching the topic

“What is important is uninterrupted sitting time. The recommendation is to break up those sitting times with active periods. Health professionals have already incorporated the concept of moderate to vigorous physical exercise, but nonintense activities are sufficient to reduce sitting time. Yoga may not be vigorous, but it is valuable at reducing sitting time,” said Dr. Kovalskys.

Dr. Ferrari recommended giving patients concrete messages so that they spend as little time possible sitting. “It is better to stand on the bus or the subway even when there is a place to sit. Are you going to talk on the phone? It is better to do it while walking or at least standing instead of sitting.”

A recent literature review conducted by investigators of the University of Birmingham (England) studied the possible molecular and physiologic mechanisms of inactivity time, health consequences, and protection strategies. It offers an evaluation of interventions that can compensate for the immediate negative consequences of inactivity.
 

Physical activity

Some studies suggest that more than 60 min/day of moderate-intensity exercise or more than 150 min/week of moderate to vigorous exercise may be effective at mitigating the increased risk for mortality associated with sitting time, but reduced intensity may not be enough.

Active pauses

Interrupting sitting every 30-60 min to walk or cycle (2-10 min), performing 3 minutes of simple resistance activities every 30 minutes, such as calf or knee lifts, performing intermittent leg movements (1 minute of activity for every 4 minutes of inactivity during a 3-hour protocol session), or pausing to climb stairs (5 minutes every hour) may be beneficial for vascular health. However, not all studies have demonstrated these positive effects, therefore, some populations may need exercise of greater intensity or duration to counteract the negative vascular effects of acute inactivity periods.

Standing workstations

Standing workstations are effective at reducing sitting time in offices but may be ineffective at reducing vascular alterations related to sitting time. Although some experimental studies indicate vascular benefits, epidemiologic studies suggest that long periods of standing can be harmful to vascular health, especially for venous diseases. Recommendations for use should be accompanied by specific regimens on the frequency and duration of the position to attain the maximum benefits and minimize other vascular complications.

One problem that Dr. Lobelo noted is that some doctors ask their patients how active they are, but they do so in a nonstandardized manner. This observation led him to publish, together with the American Heart Association, an article on the importance for health systems of considering physical activity as a vital sign and including it in records in a standardized manner.

He said that “one advantage of having physical activity as a vital sign in patient medical records is that it allows us to identify individuals who are at greater risk.”

Kaiser Permanente asks the following questions: how many minutes of physical activity do you perform regularly per week, and what is the average intensity of that activity? Patients can be classified into the following three groups: those who follow the recommendations, those with almost no activity, and those who perform some physical activity but do not meet the recommended 150 min/week of moderate to vigorous activity.

Recording sitting time is more difficult. Dr. Lobelo indicated that “it is easier for a person to remember how much time they spent running than how long they were sitting.” Regarding the use of technology, he commented that most watches provide a good estimate. Without technology, it can be estimated by asking how much time is spent in the car, on the bus, or in front of the computer or television and then adding up these times.

Dr. Lobelo emphasized that the two behaviors, lack of physical activity and excessive sitting time, have independent associations with health outcomes. But if both are combined, the risk of obesity, diabetes, and cardiovascular diseases is not just added but rather is multiplied. These behaviors contribute to the epidemic of obesity and diabetes, since most people do not follow either of the two recommendations.

“Studies show that of the two behaviors, the more negative for health would be not following the physical activity recommendations,” said Dr. Lobelo. “If the recommendation of 150 min/week of moderate to vigorous physical activity is followed, the associated risk of sitting too much declines by 80%-90%. Additionally, we can prevent, help to manage, and decrease the risk of complications in more than 100 diseases, including infections. During the pandemic, it was observed that more active people had a lower risk of dying or of being hospitalized due to COVID-19 than less active people, independently of other factors, such as hypertension, diabetes, and obesity.”

Moreover, Dr. Lobelo believes in “practicing what you preach” and advocates that doctors become healthy models.

Dr. Lobelo, Dr. Ferrari, and Dr. Kovalskys disclosed no relevant financial relationships.

This article was translated from the Medscape Spanish edition. A version appeared on Medscape.com.

Sitting for more than 8 hours per day increases the chances of becoming overweight or obese, unlike sitting for only 4 hours per day, according to a recent Latin American study published in BMC Public Health.

These data come from almost 8,000 people aged 20-65 years (half of whom are women) who participated in the Latin American Study on Nutrition and Health (ELANS). The cross-sectional survey included representative samples from urban populations in Argentina, Brazil, Chile, Colombia, Costa Rica, Ecuador, Peru, and Venezuela. The average time spent sitting was 420 min/d. Ecuador had the lowest time (300 min/day), and Argentina and Peru had the highest (480 min/day).

No amount of sitting time has been associated with a greater health risk, but the World Health Organization recommends that sitting time be minimal.

“We used to believe that any intense physical exercise could compensate for a sedentary life. But now we know that a sedentary lifestyle in general and sitting time in particular have a direct effect and are an independent risk factor for chronic diseases,” said study author Irina Kovalskys, PhD, a pediatric specialist in nutrition and a professor of nutrition at the Catholic University of Argentina, Buenos Aires, and a principal investigator of ELANS.

Dr. Kovalskys stated that the 420-min average sitting time is worrying in a population such as the one studied, in which 60% of adults are obese and there are high rates of cardiometabolic risk factors. She affirmed that it is important to raise awareness among the population and focus on adolescents.

Felipe Lobelo, PhD, is a Colombian physician, an associate professor of global health at Emory University and director of epidemiology at Kaiser Permanente Georgia, both in Atlanta. He did not participate in this study but promotes the concept of exercise in medicine. The activity of the patient must be included in a clinical setting, and improving the level of physical activity can have a positive impact on health prognosis, he said.

“To make public health recommendations or even advise patients, a cutoff point is needed. Guidelines recommend 150 minutes per week of moderate to vigorous physical activity, and some countries have started to indicate that we should be concerned about people’s sitting time. There is still no equivalent to the 150 minutes, therefore, these studies are important, especially in the Latin American population,” said Dr. Lobelo.

He explained that the concept of an increased risk of death or chronic disease because of a lack of physical activity arose in the past 50 years, but only in the past 2 decades have we started thinking about sitting time.

“Spending more than 8 hours sitting per day clearly causes a much higher risk of chronic diseases, including obesity and diabetes. It may be a continuous and progressive association, and the point at which this increase becomes exponential is clearly between 6 and 8 hours of sitting time,” Dr. Lobelo added.

The authors expected to find a linear association with risk for being overweight or obese after 4 hours, but they did not find one. “This study has limitations. Among them was that other indicators were not considered, such as health indicators. Collaborations are starting with other research groups, and other studies are being designed,” said study author Gerson Ferrari, PhD, an associate professor at Santiago de Chile University.
 

Comparing indicators

The Latin American study tried to establish a sitting cutoff time after which the risk of becoming overweight or obese increases. It used three indicators of excess weight: body mass index (BMI), waist circumference, and neck circumference.

Sitting for more than 8 hours increased the chances of excess weight by 10% when measured by BMI and by 13% when neck circumference was used.

Dr. Ferrari stated that the result obtained measuring BMI is the one that should be considered, because it is used in public policy. Neck circumference is a more recent measurement of detection and it is less studied, but it is a valid indicator, with good sensitivity and advantages over others, such as ease of measurement and lack of variation over time.

According to the results of this study, measuring neck circumference may be the most sensitive method of the three. Neck circumference was proportionally greater in people who sat for at least 4, at least 6, and at least 8 hours/day than in those who sat for less than 4, less than 6, and less than 8 hours/day. This relationship was not observed with the other indicators.
 

Broaching the topic

“What is important is uninterrupted sitting time. The recommendation is to break up those sitting times with active periods. Health professionals have already incorporated the concept of moderate to vigorous physical exercise, but nonintense activities are sufficient to reduce sitting time. Yoga may not be vigorous, but it is valuable at reducing sitting time,” said Dr. Kovalskys.

Dr. Ferrari recommended giving patients concrete messages so that they spend as little time possible sitting. “It is better to stand on the bus or the subway even when there is a place to sit. Are you going to talk on the phone? It is better to do it while walking or at least standing instead of sitting.”

A recent literature review conducted by investigators of the University of Birmingham (England) studied the possible molecular and physiologic mechanisms of inactivity time, health consequences, and protection strategies. It offers an evaluation of interventions that can compensate for the immediate negative consequences of inactivity.
 

Physical activity

Some studies suggest that more than 60 min/day of moderate-intensity exercise or more than 150 min/week of moderate to vigorous exercise may be effective at mitigating the increased risk for mortality associated with sitting time, but reduced intensity may not be enough.

Active pauses

Interrupting sitting every 30-60 min to walk or cycle (2-10 min), performing 3 minutes of simple resistance activities every 30 minutes, such as calf or knee lifts, performing intermittent leg movements (1 minute of activity for every 4 minutes of inactivity during a 3-hour protocol session), or pausing to climb stairs (5 minutes every hour) may be beneficial for vascular health. However, not all studies have demonstrated these positive effects, therefore, some populations may need exercise of greater intensity or duration to counteract the negative vascular effects of acute inactivity periods.

Standing workstations

Standing workstations are effective at reducing sitting time in offices but may be ineffective at reducing vascular alterations related to sitting time. Although some experimental studies indicate vascular benefits, epidemiologic studies suggest that long periods of standing can be harmful to vascular health, especially for venous diseases. Recommendations for use should be accompanied by specific regimens on the frequency and duration of the position to attain the maximum benefits and minimize other vascular complications.

One problem that Dr. Lobelo noted is that some doctors ask their patients how active they are, but they do so in a nonstandardized manner. This observation led him to publish, together with the American Heart Association, an article on the importance for health systems of considering physical activity as a vital sign and including it in records in a standardized manner.

He said that “one advantage of having physical activity as a vital sign in patient medical records is that it allows us to identify individuals who are at greater risk.”

Kaiser Permanente asks the following questions: how many minutes of physical activity do you perform regularly per week, and what is the average intensity of that activity? Patients can be classified into the following three groups: those who follow the recommendations, those with almost no activity, and those who perform some physical activity but do not meet the recommended 150 min/week of moderate to vigorous activity.

Recording sitting time is more difficult. Dr. Lobelo indicated that “it is easier for a person to remember how much time they spent running than how long they were sitting.” Regarding the use of technology, he commented that most watches provide a good estimate. Without technology, it can be estimated by asking how much time is spent in the car, on the bus, or in front of the computer or television and then adding up these times.

Dr. Lobelo emphasized that the two behaviors, lack of physical activity and excessive sitting time, have independent associations with health outcomes. But if both are combined, the risk of obesity, diabetes, and cardiovascular diseases is not just added but rather is multiplied. These behaviors contribute to the epidemic of obesity and diabetes, since most people do not follow either of the two recommendations.

“Studies show that of the two behaviors, the more negative for health would be not following the physical activity recommendations,” said Dr. Lobelo. “If the recommendation of 150 min/week of moderate to vigorous physical activity is followed, the associated risk of sitting too much declines by 80%-90%. Additionally, we can prevent, help to manage, and decrease the risk of complications in more than 100 diseases, including infections. During the pandemic, it was observed that more active people had a lower risk of dying or of being hospitalized due to COVID-19 than less active people, independently of other factors, such as hypertension, diabetes, and obesity.”

Moreover, Dr. Lobelo believes in “practicing what you preach” and advocates that doctors become healthy models.

Dr. Lobelo, Dr. Ferrari, and Dr. Kovalskys disclosed no relevant financial relationships.

This article was translated from the Medscape Spanish edition. A version appeared on Medscape.com.

Despite the profound shift in guidelines for preventing peanut allergies in infants after the landmark LEAP study, national surveys in 2021 showed that 70% of parents and caregivers said that they hadn’t heard the new recommendations, and fewer than one-third of pediatricians were following them.

Now, in a 5-year National Institutes of Health–funded study called iREACH, researchers are testing whether a two-part intervention, which includes training videos and a clinical decision support tool, helps pediatricians follow the guidelines and ultimately reduces peanut allergy.

Early results from iREACH, presented at the American Academy of Allergy, Asthma, and Immunology 2023 annual meeting in San Antonio, showed mixed results with a sharp rise in clinician knowledge of the guidelines but only a modest increase in their real-world implementation with high-risk infants.

Raising a food-allergic child while working as a pediatrician herself, Ruchi Gupta, MD, MPH, director of the Center for Food Allergy and Asthma Research at Northwestern University, Chicago, understands the importance and challenge of translating published findings into practice.

During a typical 4- to 6-month well-child visit, pediatricians must check the baby’s growth, perform a physical exam, discuss milestones, field questions about sleep and poop and colic and – if they’re up on the latest guidelines – explain why it’s important to feed peanuts early and often.

“Pediatricians get stuff from every single specialty, and guidelines are always changing,” she told this news organization.

The current feeding guidelines, published in 2017 after the landmark LEAP study, switched from “ ‘don’t introduce peanuts until age 3’ to ‘introduce peanuts now,’ ” said Dr. Gupta.

But the recommendations aren’t entirely straightforward. They require pediatricians to make an assessment when the baby is around 4 months old. If the child is high-risk (has severe eczema or an egg allergy), they need a peanut-specific immunoglobulin E (IgE) test. If the test is negative, the pediatrician should encourage peanut introduction. If positive, they should refer the child to an allergist.

“It’s a little complicated,” Dr. Gupta said.

To boost understanding and adherence, Dr. Gupta’s team created the intervention tested in the iREACH study. It includes a set of training videos, a clinical decision support tool that embeds into the electronic health record (EHR) with pop-ups reminding the physician to discuss early introduction, menus for ordering peanut IgE tests or referring to an allergist if needed, and a caregiver handout that explains how to add peanuts to the baby’s diet. (These resources can be found here.)

The study enrolled 290 pediatric clinicians at 30 local practices, examining 18,460 babies from diverse backgrounds, about one-quarter of whom were from families on public insurance. About half of the clinicians received the intervention, whereas the other half served as the control arm.

The training videos seemed effective. Clinicians’ knowledge of the guidelines rose from 72.6% at baseline to 94.5% after the intervention, and their ability to identify severe eczema went up from 63.4% to 97.6%. This translated to 70.4% success with applying the guidelines when presented various clinical scenarios, up from 29% at baseline. These results are in press at JAMA Network Open.

The next set of analyses, preliminary and unpublished, monitored real-world adherence using natural language processing to pull EHR data from 4- and 6-month well-check visits. It was “AI [artificial intelligence] for notes,” Dr. Gupta said.

For low-risk infants, the training and EHR-embedded support tool greatly improved clinician adherence. Eighty percent of clinicians in the intervention arm followed the guidelines, compared with 26% in the control group.

In high-risk infants, the impact was much weaker. Even after the video-based training, only 17% of pediatric clinicians followed the guidelines – that is, ordered a peanut IgE test or referred to an allergist – compared with 8% in the control group.

Why such a low uptake?

Pediatricians are time-pressed. “How do you add [early introduction] to the other 10 or 15 things you want to talk to a parent about at the 4-month visit?” said Jonathan Necheles, MD, MPH, a pediatrician at Children’s Healthcare Associates in Chicago.

It can also be hard to tell if a baby’s eczema is “severe” or “mild to moderate.” The EHR-integrated support tool included a scorecard for judging eczema severity across a range of skin tones. The condition can be hard to recognize in patients of color. “You don’t get the redness in the same way,” said Dr. Necheles, who worked with Dr. Gupta to develop the iREACH intervention.

Curiously, even though the AI analysis found that less than one-fifth of pediatricians put the guidelines into action for high-risk infants, 69% of them recommended peanut introduction.

One interpretation is that busy pediatricians may be “doing the minimum” – introducing the concept of early introduction and telling parents to try it “but not giving any additional sort of guidance as far as who’s high risk, who’s low risk, who should see the allergist, who should get screened,” said Edwin Kim, MD, allergist-immunologist and director of the Food Allergy Initiative at the University of North Carolina at Chapel Hill.

The ultimate impact of iREACH has yet to be seen. “The end goal is, if pediatricians recommend, will parents follow, and will we reduce peanut allergy?” Dr. Gupta said.

Dr. Gupta consults or serves as an advisor for Genentech, Novartis, Aimmune, Allergenis, and Food Allergy Research & Education; receives research funding from Novartis, Genentech, FARE, Melchiorre Family Foundation, and Sunshine Charitable Foundation; and reports ownership interest from Yobee Care. Dr. Necheles reports no financial disclosures. Dr. Kim reports consultancy with Allergy Therapeutics, Belhaven Biopharma, Duke Clinical Research Institute, Genentech, Nutricia, and Revolo; advisory board membership with ALK, Kenota Health, and Ukko; and grant support from the National Institute of Allergy and Infectious Diseases, Immune Tolerance Network, and Food Allergy Research and Education.

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

Despite the profound shift in guidelines for preventing peanut allergies in infants after the landmark LEAP study, national surveys in 2021 showed that 70% of parents and caregivers said that they hadn’t heard the new recommendations, and fewer than one-third of pediatricians were following them.

Now, in a 5-year National Institutes of Health–funded study called iREACH, researchers are testing whether a two-part intervention, which includes training videos and a clinical decision support tool, helps pediatricians follow the guidelines and ultimately reduces peanut allergy.

Early results from iREACH, presented at the American Academy of Allergy, Asthma, and Immunology 2023 annual meeting in San Antonio, showed mixed results with a sharp rise in clinician knowledge of the guidelines but only a modest increase in their real-world implementation with high-risk infants.

Raising a food-allergic child while working as a pediatrician herself, Ruchi Gupta, MD, MPH, director of the Center for Food Allergy and Asthma Research at Northwestern University, Chicago, understands the importance and challenge of translating published findings into practice.

During a typical 4- to 6-month well-child visit, pediatricians must check the baby’s growth, perform a physical exam, discuss milestones, field questions about sleep and poop and colic and – if they’re up on the latest guidelines – explain why it’s important to feed peanuts early and often.

“Pediatricians get stuff from every single specialty, and guidelines are always changing,” she told this news organization.

The current feeding guidelines, published in 2017 after the landmark LEAP study, switched from “ ‘don’t introduce peanuts until age 3’ to ‘introduce peanuts now,’ ” said Dr. Gupta.

But the recommendations aren’t entirely straightforward. They require pediatricians to make an assessment when the baby is around 4 months old. If the child is high-risk (has severe eczema or an egg allergy), they need a peanut-specific immunoglobulin E (IgE) test. If the test is negative, the pediatrician should encourage peanut introduction. If positive, they should refer the child to an allergist.

“It’s a little complicated,” Dr. Gupta said.

To boost understanding and adherence, Dr. Gupta’s team created the intervention tested in the iREACH study. It includes a set of training videos, a clinical decision support tool that embeds into the electronic health record (EHR) with pop-ups reminding the physician to discuss early introduction, menus for ordering peanut IgE tests or referring to an allergist if needed, and a caregiver handout that explains how to add peanuts to the baby’s diet. (These resources can be found here.)

The study enrolled 290 pediatric clinicians at 30 local practices, examining 18,460 babies from diverse backgrounds, about one-quarter of whom were from families on public insurance. About half of the clinicians received the intervention, whereas the other half served as the control arm.

The training videos seemed effective. Clinicians’ knowledge of the guidelines rose from 72.6% at baseline to 94.5% after the intervention, and their ability to identify severe eczema went up from 63.4% to 97.6%. This translated to 70.4% success with applying the guidelines when presented various clinical scenarios, up from 29% at baseline. These results are in press at JAMA Network Open.

The next set of analyses, preliminary and unpublished, monitored real-world adherence using natural language processing to pull EHR data from 4- and 6-month well-check visits. It was “AI [artificial intelligence] for notes,” Dr. Gupta said.

For low-risk infants, the training and EHR-embedded support tool greatly improved clinician adherence. Eighty percent of clinicians in the intervention arm followed the guidelines, compared with 26% in the control group.

In high-risk infants, the impact was much weaker. Even after the video-based training, only 17% of pediatric clinicians followed the guidelines – that is, ordered a peanut IgE test or referred to an allergist – compared with 8% in the control group.

Why such a low uptake?

Pediatricians are time-pressed. “How do you add [early introduction] to the other 10 or 15 things you want to talk to a parent about at the 4-month visit?” said Jonathan Necheles, MD, MPH, a pediatrician at Children’s Healthcare Associates in Chicago.

It can also be hard to tell if a baby’s eczema is “severe” or “mild to moderate.” The EHR-integrated support tool included a scorecard for judging eczema severity across a range of skin tones. The condition can be hard to recognize in patients of color. “You don’t get the redness in the same way,” said Dr. Necheles, who worked with Dr. Gupta to develop the iREACH intervention.

Curiously, even though the AI analysis found that less than one-fifth of pediatricians put the guidelines into action for high-risk infants, 69% of them recommended peanut introduction.

One interpretation is that busy pediatricians may be “doing the minimum” – introducing the concept of early introduction and telling parents to try it “but not giving any additional sort of guidance as far as who’s high risk, who’s low risk, who should see the allergist, who should get screened,” said Edwin Kim, MD, allergist-immunologist and director of the Food Allergy Initiative at the University of North Carolina at Chapel Hill.

The ultimate impact of iREACH has yet to be seen. “The end goal is, if pediatricians recommend, will parents follow, and will we reduce peanut allergy?” Dr. Gupta said.

Dr. Gupta consults or serves as an advisor for Genentech, Novartis, Aimmune, Allergenis, and Food Allergy Research & Education; receives research funding from Novartis, Genentech, FARE, Melchiorre Family Foundation, and Sunshine Charitable Foundation; and reports ownership interest from Yobee Care. Dr. Necheles reports no financial disclosures. Dr. Kim reports consultancy with Allergy Therapeutics, Belhaven Biopharma, Duke Clinical Research Institute, Genentech, Nutricia, and Revolo; advisory board membership with ALK, Kenota Health, and Ukko; and grant support from the National Institute of Allergy and Infectious Diseases, Immune Tolerance Network, and Food Allergy Research and Education.

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

Despite the profound shift in guidelines for preventing peanut allergies in infants after the landmark LEAP study, national surveys in 2021 showed that 70% of parents and caregivers said that they hadn’t heard the new recommendations, and fewer than one-third of pediatricians were following them.

Now, in a 5-year National Institutes of Health–funded study called iREACH, researchers are testing whether a two-part intervention, which includes training videos and a clinical decision support tool, helps pediatricians follow the guidelines and ultimately reduces peanut allergy.

Early results from iREACH, presented at the American Academy of Allergy, Asthma, and Immunology 2023 annual meeting in San Antonio, showed mixed results with a sharp rise in clinician knowledge of the guidelines but only a modest increase in their real-world implementation with high-risk infants.

Raising a food-allergic child while working as a pediatrician herself, Ruchi Gupta, MD, MPH, director of the Center for Food Allergy and Asthma Research at Northwestern University, Chicago, understands the importance and challenge of translating published findings into practice.

During a typical 4- to 6-month well-child visit, pediatricians must check the baby’s growth, perform a physical exam, discuss milestones, field questions about sleep and poop and colic and – if they’re up on the latest guidelines – explain why it’s important to feed peanuts early and often.

“Pediatricians get stuff from every single specialty, and guidelines are always changing,” she told this news organization.

The current feeding guidelines, published in 2017 after the landmark LEAP study, switched from “ ‘don’t introduce peanuts until age 3’ to ‘introduce peanuts now,’ ” said Dr. Gupta.

But the recommendations aren’t entirely straightforward. They require pediatricians to make an assessment when the baby is around 4 months old. If the child is high-risk (has severe eczema or an egg allergy), they need a peanut-specific immunoglobulin E (IgE) test. If the test is negative, the pediatrician should encourage peanut introduction. If positive, they should refer the child to an allergist.

“It’s a little complicated,” Dr. Gupta said.

To boost understanding and adherence, Dr. Gupta’s team created the intervention tested in the iREACH study. It includes a set of training videos, a clinical decision support tool that embeds into the electronic health record (EHR) with pop-ups reminding the physician to discuss early introduction, menus for ordering peanut IgE tests or referring to an allergist if needed, and a caregiver handout that explains how to add peanuts to the baby’s diet. (These resources can be found here.)

The study enrolled 290 pediatric clinicians at 30 local practices, examining 18,460 babies from diverse backgrounds, about one-quarter of whom were from families on public insurance. About half of the clinicians received the intervention, whereas the other half served as the control arm.

The training videos seemed effective. Clinicians’ knowledge of the guidelines rose from 72.6% at baseline to 94.5% after the intervention, and their ability to identify severe eczema went up from 63.4% to 97.6%. This translated to 70.4% success with applying the guidelines when presented various clinical scenarios, up from 29% at baseline. These results are in press at JAMA Network Open.

The next set of analyses, preliminary and unpublished, monitored real-world adherence using natural language processing to pull EHR data from 4- and 6-month well-check visits. It was “AI [artificial intelligence] for notes,” Dr. Gupta said.

For low-risk infants, the training and EHR-embedded support tool greatly improved clinician adherence. Eighty percent of clinicians in the intervention arm followed the guidelines, compared with 26% in the control group.

In high-risk infants, the impact was much weaker. Even after the video-based training, only 17% of pediatric clinicians followed the guidelines – that is, ordered a peanut IgE test or referred to an allergist – compared with 8% in the control group.

Why such a low uptake?

Pediatricians are time-pressed. “How do you add [early introduction] to the other 10 or 15 things you want to talk to a parent about at the 4-month visit?” said Jonathan Necheles, MD, MPH, a pediatrician at Children’s Healthcare Associates in Chicago.

It can also be hard to tell if a baby’s eczema is “severe” or “mild to moderate.” The EHR-integrated support tool included a scorecard for judging eczema severity across a range of skin tones. The condition can be hard to recognize in patients of color. “You don’t get the redness in the same way,” said Dr. Necheles, who worked with Dr. Gupta to develop the iREACH intervention.

Curiously, even though the AI analysis found that less than one-fifth of pediatricians put the guidelines into action for high-risk infants, 69% of them recommended peanut introduction.

One interpretation is that busy pediatricians may be “doing the minimum” – introducing the concept of early introduction and telling parents to try it “but not giving any additional sort of guidance as far as who’s high risk, who’s low risk, who should see the allergist, who should get screened,” said Edwin Kim, MD, allergist-immunologist and director of the Food Allergy Initiative at the University of North Carolina at Chapel Hill.

The ultimate impact of iREACH has yet to be seen. “The end goal is, if pediatricians recommend, will parents follow, and will we reduce peanut allergy?” Dr. Gupta said.

Dr. Gupta consults or serves as an advisor for Genentech, Novartis, Aimmune, Allergenis, and Food Allergy Research & Education; receives research funding from Novartis, Genentech, FARE, Melchiorre Family Foundation, and Sunshine Charitable Foundation; and reports ownership interest from Yobee Care. Dr. Necheles reports no financial disclosures. Dr. Kim reports consultancy with Allergy Therapeutics, Belhaven Biopharma, Duke Clinical Research Institute, Genentech, Nutricia, and Revolo; advisory board membership with ALK, Kenota Health, and Ukko; and grant support from the National Institute of Allergy and Infectious Diseases, Immune Tolerance Network, and Food Allergy Research and Education.

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

Long-term assessment of suicide risk and ideation in older adults may help identify distinct ideation patterns and predict potential future suicidal behavior, new research suggests.

Investigators studied over 300 older adults, assessing suicidal ideation and behavior for up to 14 years at least once annually. They then identified four suicidal ideation profiles.

They found that risk of suicide attempt/death was almost five times greater for chronic severe ideators and more than three times greater for highly variable ideators, compared with fast-remitting ideators. In turn, fast-remitting ideators were at higher risk in comparison to low/nonideators with no attempts or suicide.

Chronic severe ideators also showed the most severe levels of dysfunction across personality, social characteristics, and impulsivity measures, while highly variable and fast-remitting ideators displayed more specific deficits.

“We identified longitudinal ideation profiles that convey differential risk of future suicidal behavior to help clinicians recognize high suicide risk patients for preventing suicide,” said lead author Hanga Galfalvy, PhD, associate professor, department of psychiatry, Columbia University Irving Medical Center, New York.

“Clinicians should repeatedly assess suicidal ideation and ask not only about current ideation but also about the worst ideation since the last visit [because] similar levels of ideation during a single assessment can belong to very different risk profiles,” said Dr. Galfalvy, also a professor of biostatistics and a coinvestigator in the Conte Center for Suicide Prevention at Columbia University.

The study was published online in the Journal of Clinical Psychiatry.
 

Vulnerable population

“Older adults in most countries, including the U.S., are at the highest risk of dying of suicide out of all age groups,” said Dr. Galfalvy. “A significant number of depressed older adults experience thoughts of killing themselves, but fortunately, only a few transition from suicidal thoughts to behavior.”

Senior author Katalin Szanto, MD, professor of psychiatry, University of Pittsburgh, said in an interview that currently established clinical and psychosocial suicide risk factors have “low predictive value and provide little insight into the high suicide rate in the elderly.”

These traditional risk factors “poorly distinguish between suicide ideators and suicide attempters and do not take into consideration the heterogeneity of suicidal behavior,” said Dr. Szanto, principal investigator at the University of Pittsburgh’s Longitudinal research Program in Late-Life Suicide, where the study was conducted.

“Suicidal ideation measured at one time point – current or lifetime – may not be enough to accurately predict suicide risk,” the investigators wrote.

The current study, a collaboration between investigators from the Longitudinal Research Program in Late-Life Suicide and the Conte Center for Suicide Prevention, investigates “profiles of suicidal thoughts and behavior in patients with late-life depression over a longer period of time,” Dr. Galfalvy said.

The researchers used latent profile analysis (LPA) in a cohort of adults with nonpsychotic unipolar depression (aged 50-93 years; n = 337; mean age, 65.12 years) to “identify distinct ideation profiles and their clinical correlates” and to “test the profiles’ association with the risk of suicidal behavior before and during follow-up.”

LPA is “a data-driven method of grouping individuals into subgroups, based on quantitative characteristics,” Dr. Galfalvy explained.

The LPA yielded four profiles of ideation.

Personalized prevention

Of the original cohort, 92 patients died during the follow-up period, with 13 dying of suicide (or suspected suicide).

Over half (60%) of the chronic severe as well as the highly variable groups and almost half (48%) of the fast-remitting group had a history of past suicide attempt – all significantly higher than the low-nonideators (0%).

Despite comparable current ideation severity at baseline, the risk of suicide attempt/death was greater for chronic severe ideators versus fast-remitting ideators, but not greater than for highly variable ideators. On the other hand, highly variable ideators were at greater risk, compared with fast-remitting ideators.

New insight

Commenting on the study, Ari Cuperfain, MD, of the University of Toronto said the study “adds to the nuanced understanding of how changes in suicidal ideation over time can lead to suicidal actions and behavior.”

The study “sheds light on the notion of how older adults who die by suicide can demonstrate a greater degree of premeditated intent relative to younger cohorts, with chronic severe ideators portending the highest risk for suicide in this sample,” added Dr. Cuperfain, who was not involved with the current research.

“Overall, the paper highlights the importance of both screening for current levels of suicidal ideation in addition to the evolution of suicidal ideation in developing a risk assessment and in finding interventions to reduce this risk when it is most prominent,” he stated.

The research was supported by the National Institutes of Health. The authors and Dr. Cuperfain disclosed no relevant financial relationships.

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

Long-term assessment of suicide risk and ideation in older adults may help identify distinct ideation patterns and predict potential future suicidal behavior, new research suggests.

Investigators studied over 300 older adults, assessing suicidal ideation and behavior for up to 14 years at least once annually. They then identified four suicidal ideation profiles.

They found that risk of suicide attempt/death was almost five times greater for chronic severe ideators and more than three times greater for highly variable ideators, compared with fast-remitting ideators. In turn, fast-remitting ideators were at higher risk in comparison to low/nonideators with no attempts or suicide.

Chronic severe ideators also showed the most severe levels of dysfunction across personality, social characteristics, and impulsivity measures, while highly variable and fast-remitting ideators displayed more specific deficits.

“We identified longitudinal ideation profiles that convey differential risk of future suicidal behavior to help clinicians recognize high suicide risk patients for preventing suicide,” said lead author Hanga Galfalvy, PhD, associate professor, department of psychiatry, Columbia University Irving Medical Center, New York.

“Clinicians should repeatedly assess suicidal ideation and ask not only about current ideation but also about the worst ideation since the last visit [because] similar levels of ideation during a single assessment can belong to very different risk profiles,” said Dr. Galfalvy, also a professor of biostatistics and a coinvestigator in the Conte Center for Suicide Prevention at Columbia University.

The study was published online in the Journal of Clinical Psychiatry.
 

Vulnerable population

“Older adults in most countries, including the U.S., are at the highest risk of dying of suicide out of all age groups,” said Dr. Galfalvy. “A significant number of depressed older adults experience thoughts of killing themselves, but fortunately, only a few transition from suicidal thoughts to behavior.”

Senior author Katalin Szanto, MD, professor of psychiatry, University of Pittsburgh, said in an interview that currently established clinical and psychosocial suicide risk factors have “low predictive value and provide little insight into the high suicide rate in the elderly.”

These traditional risk factors “poorly distinguish between suicide ideators and suicide attempters and do not take into consideration the heterogeneity of suicidal behavior,” said Dr. Szanto, principal investigator at the University of Pittsburgh’s Longitudinal research Program in Late-Life Suicide, where the study was conducted.

“Suicidal ideation measured at one time point – current or lifetime – may not be enough to accurately predict suicide risk,” the investigators wrote.

The current study, a collaboration between investigators from the Longitudinal Research Program in Late-Life Suicide and the Conte Center for Suicide Prevention, investigates “profiles of suicidal thoughts and behavior in patients with late-life depression over a longer period of time,” Dr. Galfalvy said.

The researchers used latent profile analysis (LPA) in a cohort of adults with nonpsychotic unipolar depression (aged 50-93 years; n = 337; mean age, 65.12 years) to “identify distinct ideation profiles and their clinical correlates” and to “test the profiles’ association with the risk of suicidal behavior before and during follow-up.”

LPA is “a data-driven method of grouping individuals into subgroups, based on quantitative characteristics,” Dr. Galfalvy explained.

The LPA yielded four profiles of ideation.

Personalized prevention

Of the original cohort, 92 patients died during the follow-up period, with 13 dying of suicide (or suspected suicide).

Over half (60%) of the chronic severe as well as the highly variable groups and almost half (48%) of the fast-remitting group had a history of past suicide attempt – all significantly higher than the low-nonideators (0%).

Despite comparable current ideation severity at baseline, the risk of suicide attempt/death was greater for chronic severe ideators versus fast-remitting ideators, but not greater than for highly variable ideators. On the other hand, highly variable ideators were at greater risk, compared with fast-remitting ideators.

New insight

Commenting on the study, Ari Cuperfain, MD, of the University of Toronto said the study “adds to the nuanced understanding of how changes in suicidal ideation over time can lead to suicidal actions and behavior.”

The study “sheds light on the notion of how older adults who die by suicide can demonstrate a greater degree of premeditated intent relative to younger cohorts, with chronic severe ideators portending the highest risk for suicide in this sample,” added Dr. Cuperfain, who was not involved with the current research.

“Overall, the paper highlights the importance of both screening for current levels of suicidal ideation in addition to the evolution of suicidal ideation in developing a risk assessment and in finding interventions to reduce this risk when it is most prominent,” he stated.

The research was supported by the National Institutes of Health. The authors and Dr. Cuperfain disclosed no relevant financial relationships.

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

Long-term assessment of suicide risk and ideation in older adults may help identify distinct ideation patterns and predict potential future suicidal behavior, new research suggests.

Investigators studied over 300 older adults, assessing suicidal ideation and behavior for up to 14 years at least once annually. They then identified four suicidal ideation profiles.

They found that risk of suicide attempt/death was almost five times greater for chronic severe ideators and more than three times greater for highly variable ideators, compared with fast-remitting ideators. In turn, fast-remitting ideators were at higher risk in comparison to low/nonideators with no attempts or suicide.

Chronic severe ideators also showed the most severe levels of dysfunction across personality, social characteristics, and impulsivity measures, while highly variable and fast-remitting ideators displayed more specific deficits.

“We identified longitudinal ideation profiles that convey differential risk of future suicidal behavior to help clinicians recognize high suicide risk patients for preventing suicide,” said lead author Hanga Galfalvy, PhD, associate professor, department of psychiatry, Columbia University Irving Medical Center, New York.

“Clinicians should repeatedly assess suicidal ideation and ask not only about current ideation but also about the worst ideation since the last visit [because] similar levels of ideation during a single assessment can belong to very different risk profiles,” said Dr. Galfalvy, also a professor of biostatistics and a coinvestigator in the Conte Center for Suicide Prevention at Columbia University.

The study was published online in the Journal of Clinical Psychiatry.
 

Vulnerable population

“Older adults in most countries, including the U.S., are at the highest risk of dying of suicide out of all age groups,” said Dr. Galfalvy. “A significant number of depressed older adults experience thoughts of killing themselves, but fortunately, only a few transition from suicidal thoughts to behavior.”

Senior author Katalin Szanto, MD, professor of psychiatry, University of Pittsburgh, said in an interview that currently established clinical and psychosocial suicide risk factors have “low predictive value and provide little insight into the high suicide rate in the elderly.”

These traditional risk factors “poorly distinguish between suicide ideators and suicide attempters and do not take into consideration the heterogeneity of suicidal behavior,” said Dr. Szanto, principal investigator at the University of Pittsburgh’s Longitudinal research Program in Late-Life Suicide, where the study was conducted.

“Suicidal ideation measured at one time point – current or lifetime – may not be enough to accurately predict suicide risk,” the investigators wrote.

The current study, a collaboration between investigators from the Longitudinal Research Program in Late-Life Suicide and the Conte Center for Suicide Prevention, investigates “profiles of suicidal thoughts and behavior in patients with late-life depression over a longer period of time,” Dr. Galfalvy said.

The researchers used latent profile analysis (LPA) in a cohort of adults with nonpsychotic unipolar depression (aged 50-93 years; n = 337; mean age, 65.12 years) to “identify distinct ideation profiles and their clinical correlates” and to “test the profiles’ association with the risk of suicidal behavior before and during follow-up.”

LPA is “a data-driven method of grouping individuals into subgroups, based on quantitative characteristics,” Dr. Galfalvy explained.

The LPA yielded four profiles of ideation.

Personalized prevention

Of the original cohort, 92 patients died during the follow-up period, with 13 dying of suicide (or suspected suicide).

Over half (60%) of the chronic severe as well as the highly variable groups and almost half (48%) of the fast-remitting group had a history of past suicide attempt – all significantly higher than the low-nonideators (0%).

Despite comparable current ideation severity at baseline, the risk of suicide attempt/death was greater for chronic severe ideators versus fast-remitting ideators, but not greater than for highly variable ideators. On the other hand, highly variable ideators were at greater risk, compared with fast-remitting ideators.

New insight

Commenting on the study, Ari Cuperfain, MD, of the University of Toronto said the study “adds to the nuanced understanding of how changes in suicidal ideation over time can lead to suicidal actions and behavior.”

The study “sheds light on the notion of how older adults who die by suicide can demonstrate a greater degree of premeditated intent relative to younger cohorts, with chronic severe ideators portending the highest risk for suicide in this sample,” added Dr. Cuperfain, who was not involved with the current research.

“Overall, the paper highlights the importance of both screening for current levels of suicidal ideation in addition to the evolution of suicidal ideation in developing a risk assessment and in finding interventions to reduce this risk when it is most prominent,” he stated.

The research was supported by the National Institutes of Health. The authors and Dr. Cuperfain disclosed no relevant financial relationships.

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

NEW ORLEANS – EHR-embedded alerts that a patient with heart failure with reduced ejection fraction (HFrEF) is a great candidate for treatment with a mineralocorticoid receptor antagonist (MRA) more than doubled prescribing of this “pillar” class for HFrEF, compared with control practices that used usual care and no alerts.

That’s according to results of BETTER CARE-HF, a single-center, randomized trial with more than 2,000 patients and involving 180 cardiologists.

“EHR-embedded tools cans be a rapid, low-cost, and high-impact method to increase prescription of life-saving therapies across large populations,” said Amrita Mukhopadhyay, MD, at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.

Mitchel L. Zoler/MDedge News

Her study targeted underprescribing of an MRA – spironolactone or eplerenone (Inspra) – because of its “vastly underprescribed” status in U.S. practice, where roughly two-thirds of patients with HFrEF do not receive an MRA despite clear recommendations from several medical groups that it is an essential part of treatment for most patients with HFrEF. Dr. Mukhopadhyay estimated that more comprehensive prescribing of MRAs to U.S. patients with HFrEF could prevent more than 20,000 deaths annually.

She also explained that the EHR-embedded alert was carefully devised, through interviews with cardiologists and pilot testing, to optimize the nudge so that it was less intrusive but effective for capturing attention and initiating action.

‘Clinically relevant, impressive results’

“This is a really important study, because despite overwhelming evidence for more than a decade favoring MRA use for patients with HFrEF there is an incredibly large treatment gap. MRAs can reduce all-cause death in people with HFrEF by 25%-30%, as well as reduce hospitalizations for heart failure, at a cost of less than $50 a year,” commented Gregg C. Fonarow, MD, interim chief of cardiology at the University of California, Los Angeles. The study showed “very clinically relevant, impressive results” for individualized, patient-specific alerts to prescribe an MRA and order the laboratory tests, particularly for serum potassium levels, needed to safely start the treatment, Dr. Fonarow said in an interview.

The BETTER CARE-HF study ran at more than 60 practices in the New York City region operated by the NYU Langone Health system, which sponsored the study. The trial randomized 180 cardiologists from these practices in a cluster format to one of three study arms: Sixty cardiologists received the EHR-embedded alerts for their relevant patients (755 patients) when the patient was in the physician’s office; another 60 cardiologists received a less tailored, monthly message that flagged all patients with HFrEF in a cardiologist’s practice who remained untreated candidates for MRA intervention (812 patients); and a third arm of 60 cardiologists and their HFrEF patients served as controls where the clinicians received no alert or message (644 patients).

The study included 2,211 patients with HFrEF and not on MRA treatment at baseline who were all identified as good candidates for starting treatment with the class, with no contraindications, no preexisting hyperkalemia, and no advanced-stage renal dysfunction.

The study’s primary outcome was the percentage of patients in each subgroup who received a new prescription for an MRA. This occurred in 29.6% of the patients whose physicians received an alert, in 15.6% of the patients whose physicians received a monthly message, and in 11.7% of patients in the control practices. Statistical analyses showed that the alerts led to a significant 2.53-fold increase in MRA prescribing, while the messages linked with a significant 67% increase in prescribing, compared with the control practices, reported Dr. Mukhopadhyay, a health services researcher at NYU Langone Health in New York. Simultaneously with her report, the results also appeared in the Journal of the American College of Cardiology.

The findings also showed that the alert and message had no significant impact on the prescribing of any other medication classes for HFrEF, compared with the controls. And the alert intervention had minimal adverse effects. While patients in the alert arm showed a significant, 45% relative increase in the incidence of hyperkalemia episodes, compared with control patients (because of a 4.5% absolute increase in hyperkalemia events), the rate of “significant” hyperkalemia with a value of at least 5.5 mmol/L, occurred in 5.0% of patients in the alert group and 5.1% of patients in the control arm.

Potassium testing poses another barrier

Even though the alerts substantially improved MRA prescribing, 70% of patients deemed MRA eligible in the alert subgroup still failed to receive a prescription. One additional barrier specific to MRA prescribing is the need it triggers for serial laboratory testing to monitor serum potassium levels. “Potassium testing generates additional work outside the index visit, which along with the risk for hyperkalemia exists as a barrier,” commented Lee R. Goldberg, MD, a heart failure specialist and professor at the University of Pennsylvania in Philadelphia. “This may be the next aspect to focus on to improve MRA uptake,” he said as a designated discussant for the report.

Mitchel L. Zoler/MDedge News

“It’s not enough to just prompt medication treatment. We also need to prompt appropriate laboratory testing,” noted Dr. Fonarow.

He also said that the approach tested by Dr. Mukhopadhyay could now be expanded to outpatient cardiologists. “The onus is on everyone involved in caring for patients with HFrEF failure to explain why maximum effort is not being made to deploy” all of the guideline-directed medical therapies for the disorder.

EHR alerts “are one way to bridge the prescribing gap, but we need multiple approaches so that all eligible patients receive guideline-directed medical therapy,” Dr. Fonarow said.

BETTER CARE-HF received no commercial funding, and Dr. Mukhopadhyay had no disclosures. Dr. Fonarow has been a consultant to AstraZeneca, Amgen, Cytokinetics, Lilly, Merck, Novartis, and Pfizer. Dr. Goldberg has received personal fees from Abbott, VisCardia, and Zoll/Respircardia.

NEW ORLEANS – EHR-embedded alerts that a patient with heart failure with reduced ejection fraction (HFrEF) is a great candidate for treatment with a mineralocorticoid receptor antagonist (MRA) more than doubled prescribing of this “pillar” class for HFrEF, compared with control practices that used usual care and no alerts.

That’s according to results of BETTER CARE-HF, a single-center, randomized trial with more than 2,000 patients and involving 180 cardiologists.

“EHR-embedded tools cans be a rapid, low-cost, and high-impact method to increase prescription of life-saving therapies across large populations,” said Amrita Mukhopadhyay, MD, at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.

Mitchel L. Zoler/MDedge News

Her study targeted underprescribing of an MRA – spironolactone or eplerenone (Inspra) – because of its “vastly underprescribed” status in U.S. practice, where roughly two-thirds of patients with HFrEF do not receive an MRA despite clear recommendations from several medical groups that it is an essential part of treatment for most patients with HFrEF. Dr. Mukhopadhyay estimated that more comprehensive prescribing of MRAs to U.S. patients with HFrEF could prevent more than 20,000 deaths annually.

She also explained that the EHR-embedded alert was carefully devised, through interviews with cardiologists and pilot testing, to optimize the nudge so that it was less intrusive but effective for capturing attention and initiating action.

‘Clinically relevant, impressive results’

“This is a really important study, because despite overwhelming evidence for more than a decade favoring MRA use for patients with HFrEF there is an incredibly large treatment gap. MRAs can reduce all-cause death in people with HFrEF by 25%-30%, as well as reduce hospitalizations for heart failure, at a cost of less than $50 a year,” commented Gregg C. Fonarow, MD, interim chief of cardiology at the University of California, Los Angeles. The study showed “very clinically relevant, impressive results” for individualized, patient-specific alerts to prescribe an MRA and order the laboratory tests, particularly for serum potassium levels, needed to safely start the treatment, Dr. Fonarow said in an interview.

The BETTER CARE-HF study ran at more than 60 practices in the New York City region operated by the NYU Langone Health system, which sponsored the study. The trial randomized 180 cardiologists from these practices in a cluster format to one of three study arms: Sixty cardiologists received the EHR-embedded alerts for their relevant patients (755 patients) when the patient was in the physician’s office; another 60 cardiologists received a less tailored, monthly message that flagged all patients with HFrEF in a cardiologist’s practice who remained untreated candidates for MRA intervention (812 patients); and a third arm of 60 cardiologists and their HFrEF patients served as controls where the clinicians received no alert or message (644 patients).

The study included 2,211 patients with HFrEF and not on MRA treatment at baseline who were all identified as good candidates for starting treatment with the class, with no contraindications, no preexisting hyperkalemia, and no advanced-stage renal dysfunction.

The study’s primary outcome was the percentage of patients in each subgroup who received a new prescription for an MRA. This occurred in 29.6% of the patients whose physicians received an alert, in 15.6% of the patients whose physicians received a monthly message, and in 11.7% of patients in the control practices. Statistical analyses showed that the alerts led to a significant 2.53-fold increase in MRA prescribing, while the messages linked with a significant 67% increase in prescribing, compared with the control practices, reported Dr. Mukhopadhyay, a health services researcher at NYU Langone Health in New York. Simultaneously with her report, the results also appeared in the Journal of the American College of Cardiology.

The findings also showed that the alert and message had no significant impact on the prescribing of any other medication classes for HFrEF, compared with the controls. And the alert intervention had minimal adverse effects. While patients in the alert arm showed a significant, 45% relative increase in the incidence of hyperkalemia episodes, compared with control patients (because of a 4.5% absolute increase in hyperkalemia events), the rate of “significant” hyperkalemia with a value of at least 5.5 mmol/L, occurred in 5.0% of patients in the alert group and 5.1% of patients in the control arm.

Potassium testing poses another barrier

Even though the alerts substantially improved MRA prescribing, 70% of patients deemed MRA eligible in the alert subgroup still failed to receive a prescription. One additional barrier specific to MRA prescribing is the need it triggers for serial laboratory testing to monitor serum potassium levels. “Potassium testing generates additional work outside the index visit, which along with the risk for hyperkalemia exists as a barrier,” commented Lee R. Goldberg, MD, a heart failure specialist and professor at the University of Pennsylvania in Philadelphia. “This may be the next aspect to focus on to improve MRA uptake,” he said as a designated discussant for the report.

Mitchel L. Zoler/MDedge News

“It’s not enough to just prompt medication treatment. We also need to prompt appropriate laboratory testing,” noted Dr. Fonarow.

He also said that the approach tested by Dr. Mukhopadhyay could now be expanded to outpatient cardiologists. “The onus is on everyone involved in caring for patients with HFrEF failure to explain why maximum effort is not being made to deploy” all of the guideline-directed medical therapies for the disorder.

EHR alerts “are one way to bridge the prescribing gap, but we need multiple approaches so that all eligible patients receive guideline-directed medical therapy,” Dr. Fonarow said.

BETTER CARE-HF received no commercial funding, and Dr. Mukhopadhyay had no disclosures. Dr. Fonarow has been a consultant to AstraZeneca, Amgen, Cytokinetics, Lilly, Merck, Novartis, and Pfizer. Dr. Goldberg has received personal fees from Abbott, VisCardia, and Zoll/Respircardia.

NEW ORLEANS – EHR-embedded alerts that a patient with heart failure with reduced ejection fraction (HFrEF) is a great candidate for treatment with a mineralocorticoid receptor antagonist (MRA) more than doubled prescribing of this “pillar” class for HFrEF, compared with control practices that used usual care and no alerts.

That’s according to results of BETTER CARE-HF, a single-center, randomized trial with more than 2,000 patients and involving 180 cardiologists.

“EHR-embedded tools cans be a rapid, low-cost, and high-impact method to increase prescription of life-saving therapies across large populations,” said Amrita Mukhopadhyay, MD, at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.

Mitchel L. Zoler/MDedge News

Her study targeted underprescribing of an MRA – spironolactone or eplerenone (Inspra) – because of its “vastly underprescribed” status in U.S. practice, where roughly two-thirds of patients with HFrEF do not receive an MRA despite clear recommendations from several medical groups that it is an essential part of treatment for most patients with HFrEF. Dr. Mukhopadhyay estimated that more comprehensive prescribing of MRAs to U.S. patients with HFrEF could prevent more than 20,000 deaths annually.

She also explained that the EHR-embedded alert was carefully devised, through interviews with cardiologists and pilot testing, to optimize the nudge so that it was less intrusive but effective for capturing attention and initiating action.

‘Clinically relevant, impressive results’

“This is a really important study, because despite overwhelming evidence for more than a decade favoring MRA use for patients with HFrEF there is an incredibly large treatment gap. MRAs can reduce all-cause death in people with HFrEF by 25%-30%, as well as reduce hospitalizations for heart failure, at a cost of less than $50 a year,” commented Gregg C. Fonarow, MD, interim chief of cardiology at the University of California, Los Angeles. The study showed “very clinically relevant, impressive results” for individualized, patient-specific alerts to prescribe an MRA and order the laboratory tests, particularly for serum potassium levels, needed to safely start the treatment, Dr. Fonarow said in an interview.

The BETTER CARE-HF study ran at more than 60 practices in the New York City region operated by the NYU Langone Health system, which sponsored the study. The trial randomized 180 cardiologists from these practices in a cluster format to one of three study arms: Sixty cardiologists received the EHR-embedded alerts for their relevant patients (755 patients) when the patient was in the physician’s office; another 60 cardiologists received a less tailored, monthly message that flagged all patients with HFrEF in a cardiologist’s practice who remained untreated candidates for MRA intervention (812 patients); and a third arm of 60 cardiologists and their HFrEF patients served as controls where the clinicians received no alert or message (644 patients).

The study included 2,211 patients with HFrEF and not on MRA treatment at baseline who were all identified as good candidates for starting treatment with the class, with no contraindications, no preexisting hyperkalemia, and no advanced-stage renal dysfunction.

The study’s primary outcome was the percentage of patients in each subgroup who received a new prescription for an MRA. This occurred in 29.6% of the patients whose physicians received an alert, in 15.6% of the patients whose physicians received a monthly message, and in 11.7% of patients in the control practices. Statistical analyses showed that the alerts led to a significant 2.53-fold increase in MRA prescribing, while the messages linked with a significant 67% increase in prescribing, compared with the control practices, reported Dr. Mukhopadhyay, a health services researcher at NYU Langone Health in New York. Simultaneously with her report, the results also appeared in the Journal of the American College of Cardiology.

The findings also showed that the alert and message had no significant impact on the prescribing of any other medication classes for HFrEF, compared with the controls. And the alert intervention had minimal adverse effects. While patients in the alert arm showed a significant, 45% relative increase in the incidence of hyperkalemia episodes, compared with control patients (because of a 4.5% absolute increase in hyperkalemia events), the rate of “significant” hyperkalemia with a value of at least 5.5 mmol/L, occurred in 5.0% of patients in the alert group and 5.1% of patients in the control arm.

Potassium testing poses another barrier

Even though the alerts substantially improved MRA prescribing, 70% of patients deemed MRA eligible in the alert subgroup still failed to receive a prescription. One additional barrier specific to MRA prescribing is the need it triggers for serial laboratory testing to monitor serum potassium levels. “Potassium testing generates additional work outside the index visit, which along with the risk for hyperkalemia exists as a barrier,” commented Lee R. Goldberg, MD, a heart failure specialist and professor at the University of Pennsylvania in Philadelphia. “This may be the next aspect to focus on to improve MRA uptake,” he said as a designated discussant for the report.

Mitchel L. Zoler/MDedge News

“It’s not enough to just prompt medication treatment. We also need to prompt appropriate laboratory testing,” noted Dr. Fonarow.

He also said that the approach tested by Dr. Mukhopadhyay could now be expanded to outpatient cardiologists. “The onus is on everyone involved in caring for patients with HFrEF failure to explain why maximum effort is not being made to deploy” all of the guideline-directed medical therapies for the disorder.

EHR alerts “are one way to bridge the prescribing gap, but we need multiple approaches so that all eligible patients receive guideline-directed medical therapy,” Dr. Fonarow said.

BETTER CARE-HF received no commercial funding, and Dr. Mukhopadhyay had no disclosures. Dr. Fonarow has been a consultant to AstraZeneca, Amgen, Cytokinetics, Lilly, Merck, Novartis, and Pfizer. Dr. Goldberg has received personal fees from Abbott, VisCardia, and Zoll/Respircardia.

NEW ORLEANS – Atorvastatin treatment of patients with lymphoma undergoing treatment with an anthracycline significantly cut the incidence of incident cardiac dysfunction by about two-thirds during 12 months of treatment, in a multicenter, randomized trial with 300 enrolled patients.

“These data support the use of atorvastatin among patients with lymphoma being treated with anthracyclines where prevention of cardiac systolic dysfunction is important,” concluded Tomas G. Neilan, MD, at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.

Mitchel L. Zoler/MDedge News

He highlighted that an important difference between the new study, STOP-CA, and a major prior study with a neutral effect published in 2022, was that STOP-CA “was powered for a major change” in cardiac function as the study’s primary outcome, a decline from baseline in left ventricular ejection fraction (LVEF) of at least 10% that also reduced ejection fraction to less than 55%.

“We can consider these medications [atorvastatin] for patients at higher risk for cardiac toxicity from anthracyclines, such as patients who receive a higher dose of an anthracycline, older patients, people with obesity, and women, commented Anita Deswal, MD, professor and chair of the department of cardiology at the University of Texas MD Anderson Cancer Center, Houston, who was not involved with the study.
 

A basis for an ‘important discussion’ with patients

“For patients receiving higher doses of anthracyclines, the STOP-CA trial says that whether to start a statin for cardiac protection is now an important discussion” for these patients to have with their treating clinicians. ”That was not the case before today,” commented Ronald M. Witteles, MD, a cardiologist and professor who specializes in cardio-oncology at Stanford (Calif.) University.

“For a patient being treated for lymphoma or for another cancer and treated with equal or higher anthracycline doses, such as patients with a sarcoma, this trial’s results at the very least warrant a discussion between physicians and patients to make the decision,” Dr. Witteles, who was not involved in the study, said in an interview. But he also cautioned that “whether an individual patient should take a statin in this scenario is still not a no-brainer. While the trial was positive, it was for an imaging rather than for a clinical endpoint.”

Experts noted that a similar study with the clinical endpoint of heart failure would require both many more randomized patients as well as much longer follow-up. STOP-CA was not powered for this endpoint. During its 12-month duration, a total of 11 patients developed heart failure, with no between group difference.

STOP-CA enrolled adults with lymphoma (Hodgkin or non-Hodgkin) and scheduled to undergo anthracycline treatment at eight U.S. centers and one in Canada, and excluded patients already on statin treatment or those for whom a statin was already indicated. Of the 300 enrolled patients, 286 had 12-month follow-up. Randomization assigned patients to receive either 40 mg daily of atorvastatin or placebo.

Their cumulative, median anthracycline dose was 300 mg/m², which is typical for treating lymphoma, but higher than the typical dose use for patients with breast cancer. At baseline, average LVEF was 63%, and after 12 months this had declined to 59%. Forty-six of the 286 patients assessed after 12 months fulfilled the primary outcome of at least a 10–percentage point reduction from baseline in their LVEF and a decline in LVEF to less than 55%. Researchers used cardiac MR to assess LVEF at baseline, and in most patients at follow-up, but a minority of patients had their follow-up assessments by echocardiography because of logistical issues. Greater than 90% of patients were adherent to their assigned regimen.

Tripled incidence of cardiac dysfunction in placebo patients

The incidence of this outcome was 9% among the patients who received atorvastatin, and 22% among those on placebo, a significant difference. The calculated odds of the primary outcome was 2.9-fold more likely among the patients treated with placebo, compared with those who received atorvastatin, also a significant difference.

The study’s secondary outcome was patients who had at least a 5% drop from baseline in their LVEF and with a LVEF of less than 55% after 12 months. This outcome occurred in 13% of patients treated with atorvastatin and in 29% of those who received placebo, a significant difference.

The atorvastatin and placebo arms showed no significant differences in adverse events during the study, with roughly similar incidence rates for muscle pain, elevated liver enzymes, and renal failure. None of the enrolled patients developed myositis.

Atorvastatin treatment also produced an expected average 37% decline from baseline in levels of LDL cholesterol.

“This was a well-designed and important trial,” said Dr. Witteles. “Anthracyclines remain a mainstay of cancer therapies for a number of malignancies, such as lymphoma and sarcoma, and the cardiac side effects of development of cardiac dysfunction are unequivocally real.”
 

The importance of a clinically meaningful effect

The results especially contrast with the findings from the PREVENT study, published in 2022, which compared a daily, 40-mg atorvastatin treatment with placebo in 279 randomized patients with breast cancer and treated for 24 months. However, patients in PREVENT had a cumulative, median anthracycline dose of 240 mg/m², and the study’s primary outcome was the average change from baseline in LVEF after 24 months of treatment, which was a reduction of 0.08 percentage points in the placebo arm, a nonsignificant difference.

In STOP-CA, the average change in LVEF from baseline was a 1–percentage point reduction in the placebo arm, compared with the atorvastatin-treated patients, a difference that was statistically significant, but “not clinically significant,” said Dr. Neilan, director of the cardio-oncology program at Massachusetts General Hospital, Boston. He cited the good fortune of the STOP-CA investigators when they received a recommendation from reviewers early on to design their study to track a clinically meaningful change in LVEF rather than just looking at the average overall change.

Mitchel L. Zoler/MDedge News

Dr. Deswal also noted that it is unlikely that future studies will examine the efficacy of a statin for preventing LVEF in patients across the range of cancers that are eligible for anthracycline treatment. As a result, she predicted that “we may have to extrapolate” the results from STOP-CA to patients with other cancer types.

STOP-CA received no commercial funding. Dr. Neilan has been a consultant for and received fees from Abbvie, Amgen, Bristol-Myers Squibb, CRC Oncology, Genentech, Roche, and Sanofi, and has received grant funding from AstraZeneca and Bristol Myers Squib. Dr. Deswal and Dr. Witteles had no relevant disclosures.

NEW ORLEANS – Atorvastatin treatment of patients with lymphoma undergoing treatment with an anthracycline significantly cut the incidence of incident cardiac dysfunction by about two-thirds during 12 months of treatment, in a multicenter, randomized trial with 300 enrolled patients.

“These data support the use of atorvastatin among patients with lymphoma being treated with anthracyclines where prevention of cardiac systolic dysfunction is important,” concluded Tomas G. Neilan, MD, at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.

Mitchel L. Zoler/MDedge News

He highlighted that an important difference between the new study, STOP-CA, and a major prior study with a neutral effect published in 2022, was that STOP-CA “was powered for a major change” in cardiac function as the study’s primary outcome, a decline from baseline in left ventricular ejection fraction (LVEF) of at least 10% that also reduced ejection fraction to less than 55%.

“We can consider these medications [atorvastatin] for patients at higher risk for cardiac toxicity from anthracyclines, such as patients who receive a higher dose of an anthracycline, older patients, people with obesity, and women, commented Anita Deswal, MD, professor and chair of the department of cardiology at the University of Texas MD Anderson Cancer Center, Houston, who was not involved with the study.
 

A basis for an ‘important discussion’ with patients

“For patients receiving higher doses of anthracyclines, the STOP-CA trial says that whether to start a statin for cardiac protection is now an important discussion” for these patients to have with their treating clinicians. ”That was not the case before today,” commented Ronald M. Witteles, MD, a cardiologist and professor who specializes in cardio-oncology at Stanford (Calif.) University.

“For a patient being treated for lymphoma or for another cancer and treated with equal or higher anthracycline doses, such as patients with a sarcoma, this trial’s results at the very least warrant a discussion between physicians and patients to make the decision,” Dr. Witteles, who was not involved in the study, said in an interview. But he also cautioned that “whether an individual patient should take a statin in this scenario is still not a no-brainer. While the trial was positive, it was for an imaging rather than for a clinical endpoint.”

Experts noted that a similar study with the clinical endpoint of heart failure would require both many more randomized patients as well as much longer follow-up. STOP-CA was not powered for this endpoint. During its 12-month duration, a total of 11 patients developed heart failure, with no between group difference.

STOP-CA enrolled adults with lymphoma (Hodgkin or non-Hodgkin) and scheduled to undergo anthracycline treatment at eight U.S. centers and one in Canada, and excluded patients already on statin treatment or those for whom a statin was already indicated. Of the 300 enrolled patients, 286 had 12-month follow-up. Randomization assigned patients to receive either 40 mg daily of atorvastatin or placebo.

Their cumulative, median anthracycline dose was 300 mg/m², which is typical for treating lymphoma, but higher than the typical dose use for patients with breast cancer. At baseline, average LVEF was 63%, and after 12 months this had declined to 59%. Forty-six of the 286 patients assessed after 12 months fulfilled the primary outcome of at least a 10–percentage point reduction from baseline in their LVEF and a decline in LVEF to less than 55%. Researchers used cardiac MR to assess LVEF at baseline, and in most patients at follow-up, but a minority of patients had their follow-up assessments by echocardiography because of logistical issues. Greater than 90% of patients were adherent to their assigned regimen.

Tripled incidence of cardiac dysfunction in placebo patients

The incidence of this outcome was 9% among the patients who received atorvastatin, and 22% among those on placebo, a significant difference. The calculated odds of the primary outcome was 2.9-fold more likely among the patients treated with placebo, compared with those who received atorvastatin, also a significant difference.

The study’s secondary outcome was patients who had at least a 5% drop from baseline in their LVEF and with a LVEF of less than 55% after 12 months. This outcome occurred in 13% of patients treated with atorvastatin and in 29% of those who received placebo, a significant difference.

The atorvastatin and placebo arms showed no significant differences in adverse events during the study, with roughly similar incidence rates for muscle pain, elevated liver enzymes, and renal failure. None of the enrolled patients developed myositis.

Atorvastatin treatment also produced an expected average 37% decline from baseline in levels of LDL cholesterol.

“This was a well-designed and important trial,” said Dr. Witteles. “Anthracyclines remain a mainstay of cancer therapies for a number of malignancies, such as lymphoma and sarcoma, and the cardiac side effects of development of cardiac dysfunction are unequivocally real.”
 

The importance of a clinically meaningful effect

The results especially contrast with the findings from the PREVENT study, published in 2022, which compared a daily, 40-mg atorvastatin treatment with placebo in 279 randomized patients with breast cancer and treated for 24 months. However, patients in PREVENT had a cumulative, median anthracycline dose of 240 mg/m², and the study’s primary outcome was the average change from baseline in LVEF after 24 months of treatment, which was a reduction of 0.08 percentage points in the placebo arm, a nonsignificant difference.

In STOP-CA, the average change in LVEF from baseline was a 1–percentage point reduction in the placebo arm, compared with the atorvastatin-treated patients, a difference that was statistically significant, but “not clinically significant,” said Dr. Neilan, director of the cardio-oncology program at Massachusetts General Hospital, Boston. He cited the good fortune of the STOP-CA investigators when they received a recommendation from reviewers early on to design their study to track a clinically meaningful change in LVEF rather than just looking at the average overall change.

Mitchel L. Zoler/MDedge News

Dr. Deswal also noted that it is unlikely that future studies will examine the efficacy of a statin for preventing LVEF in patients across the range of cancers that are eligible for anthracycline treatment. As a result, she predicted that “we may have to extrapolate” the results from STOP-CA to patients with other cancer types.

STOP-CA received no commercial funding. Dr. Neilan has been a consultant for and received fees from Abbvie, Amgen, Bristol-Myers Squibb, CRC Oncology, Genentech, Roche, and Sanofi, and has received grant funding from AstraZeneca and Bristol Myers Squib. Dr. Deswal and Dr. Witteles had no relevant disclosures.

NEW ORLEANS – Atorvastatin treatment of patients with lymphoma undergoing treatment with an anthracycline significantly cut the incidence of incident cardiac dysfunction by about two-thirds during 12 months of treatment, in a multicenter, randomized trial with 300 enrolled patients.

“These data support the use of atorvastatin among patients with lymphoma being treated with anthracyclines where prevention of cardiac systolic dysfunction is important,” concluded Tomas G. Neilan, MD, at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.

Mitchel L. Zoler/MDedge News

He highlighted that an important difference between the new study, STOP-CA, and a major prior study with a neutral effect published in 2022, was that STOP-CA “was powered for a major change” in cardiac function as the study’s primary outcome, a decline from baseline in left ventricular ejection fraction (LVEF) of at least 10% that also reduced ejection fraction to less than 55%.

“We can consider these medications [atorvastatin] for patients at higher risk for cardiac toxicity from anthracyclines, such as patients who receive a higher dose of an anthracycline, older patients, people with obesity, and women, commented Anita Deswal, MD, professor and chair of the department of cardiology at the University of Texas MD Anderson Cancer Center, Houston, who was not involved with the study.
 

A basis for an ‘important discussion’ with patients

“For patients receiving higher doses of anthracyclines, the STOP-CA trial says that whether to start a statin for cardiac protection is now an important discussion” for these patients to have with their treating clinicians. ”That was not the case before today,” commented Ronald M. Witteles, MD, a cardiologist and professor who specializes in cardio-oncology at Stanford (Calif.) University.

“For a patient being treated for lymphoma or for another cancer and treated with equal or higher anthracycline doses, such as patients with a sarcoma, this trial’s results at the very least warrant a discussion between physicians and patients to make the decision,” Dr. Witteles, who was not involved in the study, said in an interview. But he also cautioned that “whether an individual patient should take a statin in this scenario is still not a no-brainer. While the trial was positive, it was for an imaging rather than for a clinical endpoint.”

Experts noted that a similar study with the clinical endpoint of heart failure would require both many more randomized patients as well as much longer follow-up. STOP-CA was not powered for this endpoint. During its 12-month duration, a total of 11 patients developed heart failure, with no between group difference.

STOP-CA enrolled adults with lymphoma (Hodgkin or non-Hodgkin) and scheduled to undergo anthracycline treatment at eight U.S. centers and one in Canada, and excluded patients already on statin treatment or those for whom a statin was already indicated. Of the 300 enrolled patients, 286 had 12-month follow-up. Randomization assigned patients to receive either 40 mg daily of atorvastatin or placebo.

Their cumulative, median anthracycline dose was 300 mg/m², which is typical for treating lymphoma, but higher than the typical dose use for patients with breast cancer. At baseline, average LVEF was 63%, and after 12 months this had declined to 59%. Forty-six of the 286 patients assessed after 12 months fulfilled the primary outcome of at least a 10–percentage point reduction from baseline in their LVEF and a decline in LVEF to less than 55%. Researchers used cardiac MR to assess LVEF at baseline, and in most patients at follow-up, but a minority of patients had their follow-up assessments by echocardiography because of logistical issues. Greater than 90% of patients were adherent to their assigned regimen.

Tripled incidence of cardiac dysfunction in placebo patients

The incidence of this outcome was 9% among the patients who received atorvastatin, and 22% among those on placebo, a significant difference. The calculated odds of the primary outcome was 2.9-fold more likely among the patients treated with placebo, compared with those who received atorvastatin, also a significant difference.

The study’s secondary outcome was patients who had at least a 5% drop from baseline in their LVEF and with a LVEF of less than 55% after 12 months. This outcome occurred in 13% of patients treated with atorvastatin and in 29% of those who received placebo, a significant difference.

The atorvastatin and placebo arms showed no significant differences in adverse events during the study, with roughly similar incidence rates for muscle pain, elevated liver enzymes, and renal failure. None of the enrolled patients developed myositis.

Atorvastatin treatment also produced an expected average 37% decline from baseline in levels of LDL cholesterol.

“This was a well-designed and important trial,” said Dr. Witteles. “Anthracyclines remain a mainstay of cancer therapies for a number of malignancies, such as lymphoma and sarcoma, and the cardiac side effects of development of cardiac dysfunction are unequivocally real.”
 

The importance of a clinically meaningful effect

The results especially contrast with the findings from the PREVENT study, published in 2022, which compared a daily, 40-mg atorvastatin treatment with placebo in 279 randomized patients with breast cancer and treated for 24 months. However, patients in PREVENT had a cumulative, median anthracycline dose of 240 mg/m², and the study’s primary outcome was the average change from baseline in LVEF after 24 months of treatment, which was a reduction of 0.08 percentage points in the placebo arm, a nonsignificant difference.

In STOP-CA, the average change in LVEF from baseline was a 1–percentage point reduction in the placebo arm, compared with the atorvastatin-treated patients, a difference that was statistically significant, but “not clinically significant,” said Dr. Neilan, director of the cardio-oncology program at Massachusetts General Hospital, Boston. He cited the good fortune of the STOP-CA investigators when they received a recommendation from reviewers early on to design their study to track a clinically meaningful change in LVEF rather than just looking at the average overall change.

Mitchel L. Zoler/MDedge News

Dr. Deswal also noted that it is unlikely that future studies will examine the efficacy of a statin for preventing LVEF in patients across the range of cancers that are eligible for anthracycline treatment. As a result, she predicted that “we may have to extrapolate” the results from STOP-CA to patients with other cancer types.

STOP-CA received no commercial funding. Dr. Neilan has been a consultant for and received fees from Abbvie, Amgen, Bristol-Myers Squibb, CRC Oncology, Genentech, Roche, and Sanofi, and has received grant funding from AstraZeneca and Bristol Myers Squib. Dr. Deswal and Dr. Witteles had no relevant disclosures.

A new approach to lowering cholesterol with the use of bempedoic acid (Nexletol, Esperion) brought about a significant reduction in cardiovascular events in patients intolerant to statins in the large phase 3, placebo-controlled CLEAR Outcomes trial.

The drug lowered LDL cholesterol by 21% in the study and reduced the composite primary endpoint, including cardiovascular death, MI, stroke, or coronary revascularization, by 13%; MI was reduced by 23% and coronary revascularization, by 19%.

The drug was also well tolerated in the mixed population of primary and secondary prevention patients unable or unwilling to take statins.

Mitchel L. Zoler/MDedge News

“These findings establish bempedoic acid as an effective approach to reduce major cardiovascular events in statin-intolerant patients,” study chair, Steven E. Nissen, MD, of the Cleveland Clinic concluded.

Dr. Nissen presented the CLEAR Outcomes trial at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.

The study was simultaneously published online in the New England Journal of Medicine. Top-line results were previously reported in December 2022.

Dr. Nissen pointed out that, while in the current study bempedoic acid was studied as monotherapy, he believes the drug will mainly be used in clinical practice in combination with ezetimibe, a combination shown to reduce LDL by 38%. “I think this is how it will be used in clinical practice. So, we can get an almost 40% LDL reduction – that’s about the same as 40 mg simvastatin or 20 mg atorvastatin – without giving a statin. And I think that’s where I see the potential of this therapy,” he said.

Dr. Nissen described statin intolerance as “a vexing problem” that prevents many patients from achieving LDL cholesterol levels associated with cardiovascular benefits.

He explained that bempedoic acid, an adenosine triphosphate citrate lyase inhibitor, inhibits hepatic cholesterol synthesis upstream of hydroxymethylglutaryl coenzyme A reductase, the enzyme inhibited by statins. Bempedoic acid is a prodrug activated in the liver, but not in peripheral tissues, resulting in a low incidence of muscle-related adverse events. Although bempedoic acid is approved for lowering LDL cholesterol, this is the first trial to assess its effects on cardiovascular outcomes.
 

CLEAR Outcomes

The CLEAR Outcomes trial included 13,970 patients (48% women) from 32 countries who were unable or unwilling to take statins owing to unacceptable adverse effects and who had, or were at high risk for, cardiovascular disease. They were randomly assigned to oral bempedoic acid, 180 mg daily, or placebo.

The mean LDL cholesterol level at baseline was 139 mg/dL in both groups, and after 6 months, the reduction in the level was greater with bempedoic acid than with placebo by 29.2 mg/dL (a 21.1% reduction).

The drug was also associated with a 22% reduction in high-sensitivity C-reactive protein.

After a median duration of follow-up of 40.6 months, the incidence of a primary endpoint (cardiovascular death, MI, stroke, or coronary revascularization) was significantly lower (by 13%) with bempedoic acid than with placebo (11.7% vs. 13.3%; hazard ratio, 0.87; P = .004).

The absolute risk reduction was 1.6 percentage points, and the number needed to treat for 40 months to prevent one event was 63.

The secondary composite endpoint of cardiovascular death/stroke/MI was reduced by 15% (8.2% vs. 9.5%; HR, 0.85; P = .006). Fatal or nonfatal MI was reduced by 23% (3.7% vs. 4.8%; HR, 0.77; P = .002), and coronary revascularization was reduced by 19% (6.2% vs. 7.6%; HR, 0.81; P = .001).

Bempedoic acid had no significant effects on fatal or nonfatal stroke, death from cardiovascular causes, and death from any cause.

Subgroup analysis showed similar results across all groups and no difference in treatment effect between men and women.

Adverse events were reported by 25% of patients in both groups, with adverse events leading to discontinuation reported by 10.8% of the bempedoic acid group and 10.4% of the placebo group.

Muscle disorders were reported in 15.0% of the bempedoic acid group versus 15.4% of the placebo group. And there was also no difference in new cases of diabetes (16.1% vs. 17.1%).

Bempedoic acid was associated with small increases in the incidence of gout (3.1% vs. 2.1%) and cholelithiasis (2.2% vs. 1.2%), and also small increases in serum creatinine, uric acid, and hepatic enzyme levels.

In the NEJM article, the authors pointed out that the concept of statin intolerance remains controversial. Some recent studies suggested that reported adverse effects represent an anticipation of harm, often described as the “nocebo” effect.

“Whether real or perceived, statin intolerance remains a vexing clinical problem that can prevent patients who are guideline eligible for statin treatment from reaching LDL cholesterol levels associated with clinical benefits. Accordingly, alternative nonstatin therapies are needed to manage the LDL cholesterol level in these patients,” they wrote.

“Management of patients unable or unwilling to take statins represents a challenging and frustrating clinical issue. Regardless whether this problem represents the ‘nocebo’ effect or actual intolerance, these high-risk patients need effective alternative therapies,” Dr. Nissen concluded. “The CLEAR Outcomes trial provides a sound rationale for use of bempedoic acid to reduce major adverse cardiovascular outcomes in patients intolerant to statins.”
 

‘Compelling findings’

Discussing the trial at the ACC late-breaking clinical trial session, Michelle O’Donoghue, MD, Brigham and Women’s Hospital, Boston, noted that this is the largest trial to date in statin-intolerant patients.

She pointed out that although the issue of statin intolerance remains controversial, adherence to statins is often not good, so this is an important patient population to study.

She said it was “quite remarkable” that 48% of the study were women, adding: “There is still much that we need to understand about why women appear to be less willing or able to tolerate statin therapy.” 

Dr. O’Donoghue concluded that the study showed “compelling findings,” and the event reduction was in line with what would be expected from the LDL cholesterol reduction, further supporting the LDL cholesterol hypothesis. 

She added: “Bempedoic acid is an important addition to our arsenal of nonstatin LDL-lowering therapies. And while it was overall well tolerated, it did not get a complete free pass, as there were some modest safety concerns.”

In an editorial accompanying the NEJM publication, John Alexander, MD, Duke Clinical Research Institute, Durham, N.C., wrote: “The compelling results of the CLEAR Outcomes trial will and should increase the use of bempedoic acid in patients with established atherosclerotic vascular disease and in those at high risk for vascular disease who are unable or unwilling to take statins.”

He warned, however, that it is premature to consider bempedoic acid as an alternative to statins. “Given the overwhelming evidence of the vascular benefits of statins, clinicians should continue their efforts to prescribe them at the maximum tolerated doses for appropriate patients, including those who may have discontinued statins because of presumed side effects.”.

Dr. Alexander also pointed out that although bempedoic acid also reduces the LDL cholesterol level in patients taking statins, the clinical benefits of bempedoic acid added to standard statin therapy are unknown. 

On the observation that bempedoic acid had no observed effect on mortality, he noted that “Many individual trials of statins have also not shown an effect of the agent on mortality; it was only through the meta-analysis of multiple clinical trials that the effects of statins on mortality became clear.”

“Bempedoic acid has now entered the list of evidence-based alternatives to statins for primary and secondary prevention in patients at high cardiovascular risk,” Dr. Alexander concluded. “The benefits of bempedoic acid are now clearer, and it is now our responsibility to translate this information into better primary and secondary prevention for more at-risk patients, who will, as a result, benefit from fewer cardiovascular events.”

In a second editorial, John F. Keaney Jr., MD, Brigham and Women’s Hospital, said the lack of a clear association between bempedoic acid and muscle disorders, new-onset diabetes, or worsening hyperglycemia is “welcome news” for statin-intolerant patients.

But he cautioned that “these data must be interpreted cautiously, because bempedoic acid, when combined with a statin, appears to enhance the occurrence of muscle symptoms. Moreover, bempedoic acid has its own reported side effects, including tendon rupture, increased uric acid levels, gout, and reduced glomerular filtration rate, which are not seen with statin use.”

In terms of drug interactions, Dr. Keaney noted that bempedoic acid can increase the circulating levels of simvastatin and pravastatin, so it should not be used in patients who are receiving these agents at doses above 20 mg and 40 mg, respectively. Similarly, bempedoic acid should not be used with fibrates other than fenofibrate because of concerns regarding cholelithiasis.

“Available data clearly indicate that bempedoic acid can be used as an adjunct to statin and nonstatin therapies (except as noted above) to produce an additional 16%-26% reduction in the LDL cholesterol level,” he added. “However, it is not yet clear to what extent adjunctive bempedoic acid will further reduce the risk of cardiovascular events.”

The CLEAR Outcomes trial was supported by Esperion Therapeutics. Dr. Nissen reported receiving grants from AbbVie, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Esperion, Novartis, and Silence Pharmaceuticals and consultancies with Amgen and Glenmark Pharmaceuticals.

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

A new approach to lowering cholesterol with the use of bempedoic acid (Nexletol, Esperion) brought about a significant reduction in cardiovascular events in patients intolerant to statins in the large phase 3, placebo-controlled CLEAR Outcomes trial.

The drug lowered LDL cholesterol by 21% in the study and reduced the composite primary endpoint, including cardiovascular death, MI, stroke, or coronary revascularization, by 13%; MI was reduced by 23% and coronary revascularization, by 19%.

The drug was also well tolerated in the mixed population of primary and secondary prevention patients unable or unwilling to take statins.

Mitchel L. Zoler/MDedge News

“These findings establish bempedoic acid as an effective approach to reduce major cardiovascular events in statin-intolerant patients,” study chair, Steven E. Nissen, MD, of the Cleveland Clinic concluded.

Dr. Nissen presented the CLEAR Outcomes trial at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.

The study was simultaneously published online in the New England Journal of Medicine. Top-line results were previously reported in December 2022.

Dr. Nissen pointed out that, while in the current study bempedoic acid was studied as monotherapy, he believes the drug will mainly be used in clinical practice in combination with ezetimibe, a combination shown to reduce LDL by 38%. “I think this is how it will be used in clinical practice. So, we can get an almost 40% LDL reduction – that’s about the same as 40 mg simvastatin or 20 mg atorvastatin – without giving a statin. And I think that’s where I see the potential of this therapy,” he said.

Dr. Nissen described statin intolerance as “a vexing problem” that prevents many patients from achieving LDL cholesterol levels associated with cardiovascular benefits.

He explained that bempedoic acid, an adenosine triphosphate citrate lyase inhibitor, inhibits hepatic cholesterol synthesis upstream of hydroxymethylglutaryl coenzyme A reductase, the enzyme inhibited by statins. Bempedoic acid is a prodrug activated in the liver, but not in peripheral tissues, resulting in a low incidence of muscle-related adverse events. Although bempedoic acid is approved for lowering LDL cholesterol, this is the first trial to assess its effects on cardiovascular outcomes.
 

CLEAR Outcomes

The CLEAR Outcomes trial included 13,970 patients (48% women) from 32 countries who were unable or unwilling to take statins owing to unacceptable adverse effects and who had, or were at high risk for, cardiovascular disease. They were randomly assigned to oral bempedoic acid, 180 mg daily, or placebo.

The mean LDL cholesterol level at baseline was 139 mg/dL in both groups, and after 6 months, the reduction in the level was greater with bempedoic acid than with placebo by 29.2 mg/dL (a 21.1% reduction).

The drug was also associated with a 22% reduction in high-sensitivity C-reactive protein.

After a median duration of follow-up of 40.6 months, the incidence of a primary endpoint (cardiovascular death, MI, stroke, or coronary revascularization) was significantly lower (by 13%) with bempedoic acid than with placebo (11.7% vs. 13.3%; hazard ratio, 0.87; P = .004).

The absolute risk reduction was 1.6 percentage points, and the number needed to treat for 40 months to prevent one event was 63.

The secondary composite endpoint of cardiovascular death/stroke/MI was reduced by 15% (8.2% vs. 9.5%; HR, 0.85; P = .006). Fatal or nonfatal MI was reduced by 23% (3.7% vs. 4.8%; HR, 0.77; P = .002), and coronary revascularization was reduced by 19% (6.2% vs. 7.6%; HR, 0.81; P = .001).

Bempedoic acid had no significant effects on fatal or nonfatal stroke, death from cardiovascular causes, and death from any cause.

Subgroup analysis showed similar results across all groups and no difference in treatment effect between men and women.

Adverse events were reported by 25% of patients in both groups, with adverse events leading to discontinuation reported by 10.8% of the bempedoic acid group and 10.4% of the placebo group.

Muscle disorders were reported in 15.0% of the bempedoic acid group versus 15.4% of the placebo group. And there was also no difference in new cases of diabetes (16.1% vs. 17.1%).

Bempedoic acid was associated with small increases in the incidence of gout (3.1% vs. 2.1%) and cholelithiasis (2.2% vs. 1.2%), and also small increases in serum creatinine, uric acid, and hepatic enzyme levels.

In the NEJM article, the authors pointed out that the concept of statin intolerance remains controversial. Some recent studies suggested that reported adverse effects represent an anticipation of harm, often described as the “nocebo” effect.

“Whether real or perceived, statin intolerance remains a vexing clinical problem that can prevent patients who are guideline eligible for statin treatment from reaching LDL cholesterol levels associated with clinical benefits. Accordingly, alternative nonstatin therapies are needed to manage the LDL cholesterol level in these patients,” they wrote.

“Management of patients unable or unwilling to take statins represents a challenging and frustrating clinical issue. Regardless whether this problem represents the ‘nocebo’ effect or actual intolerance, these high-risk patients need effective alternative therapies,” Dr. Nissen concluded. “The CLEAR Outcomes trial provides a sound rationale for use of bempedoic acid to reduce major adverse cardiovascular outcomes in patients intolerant to statins.”
 

‘Compelling findings’

Discussing the trial at the ACC late-breaking clinical trial session, Michelle O’Donoghue, MD, Brigham and Women’s Hospital, Boston, noted that this is the largest trial to date in statin-intolerant patients.

She pointed out that although the issue of statin intolerance remains controversial, adherence to statins is often not good, so this is an important patient population to study.

She said it was “quite remarkable” that 48% of the study were women, adding: “There is still much that we need to understand about why women appear to be less willing or able to tolerate statin therapy.” 

Dr. O’Donoghue concluded that the study showed “compelling findings,” and the event reduction was in line with what would be expected from the LDL cholesterol reduction, further supporting the LDL cholesterol hypothesis. 

She added: “Bempedoic acid is an important addition to our arsenal of nonstatin LDL-lowering therapies. And while it was overall well tolerated, it did not get a complete free pass, as there were some modest safety concerns.”

In an editorial accompanying the NEJM publication, John Alexander, MD, Duke Clinical Research Institute, Durham, N.C., wrote: “The compelling results of the CLEAR Outcomes trial will and should increase the use of bempedoic acid in patients with established atherosclerotic vascular disease and in those at high risk for vascular disease who are unable or unwilling to take statins.”

He warned, however, that it is premature to consider bempedoic acid as an alternative to statins. “Given the overwhelming evidence of the vascular benefits of statins, clinicians should continue their efforts to prescribe them at the maximum tolerated doses for appropriate patients, including those who may have discontinued statins because of presumed side effects.”.

Dr. Alexander also pointed out that although bempedoic acid also reduces the LDL cholesterol level in patients taking statins, the clinical benefits of bempedoic acid added to standard statin therapy are unknown. 

On the observation that bempedoic acid had no observed effect on mortality, he noted that “Many individual trials of statins have also not shown an effect of the agent on mortality; it was only through the meta-analysis of multiple clinical trials that the effects of statins on mortality became clear.”

“Bempedoic acid has now entered the list of evidence-based alternatives to statins for primary and secondary prevention in patients at high cardiovascular risk,” Dr. Alexander concluded. “The benefits of bempedoic acid are now clearer, and it is now our responsibility to translate this information into better primary and secondary prevention for more at-risk patients, who will, as a result, benefit from fewer cardiovascular events.”

In a second editorial, John F. Keaney Jr., MD, Brigham and Women’s Hospital, said the lack of a clear association between bempedoic acid and muscle disorders, new-onset diabetes, or worsening hyperglycemia is “welcome news” for statin-intolerant patients.

But he cautioned that “these data must be interpreted cautiously, because bempedoic acid, when combined with a statin, appears to enhance the occurrence of muscle symptoms. Moreover, bempedoic acid has its own reported side effects, including tendon rupture, increased uric acid levels, gout, and reduced glomerular filtration rate, which are not seen with statin use.”

In terms of drug interactions, Dr. Keaney noted that bempedoic acid can increase the circulating levels of simvastatin and pravastatin, so it should not be used in patients who are receiving these agents at doses above 20 mg and 40 mg, respectively. Similarly, bempedoic acid should not be used with fibrates other than fenofibrate because of concerns regarding cholelithiasis.

“Available data clearly indicate that bempedoic acid can be used as an adjunct to statin and nonstatin therapies (except as noted above) to produce an additional 16%-26% reduction in the LDL cholesterol level,” he added. “However, it is not yet clear to what extent adjunctive bempedoic acid will further reduce the risk of cardiovascular events.”

The CLEAR Outcomes trial was supported by Esperion Therapeutics. Dr. Nissen reported receiving grants from AbbVie, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Esperion, Novartis, and Silence Pharmaceuticals and consultancies with Amgen and Glenmark Pharmaceuticals.

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

A new approach to lowering cholesterol with the use of bempedoic acid (Nexletol, Esperion) brought about a significant reduction in cardiovascular events in patients intolerant to statins in the large phase 3, placebo-controlled CLEAR Outcomes trial.

The drug lowered LDL cholesterol by 21% in the study and reduced the composite primary endpoint, including cardiovascular death, MI, stroke, or coronary revascularization, by 13%; MI was reduced by 23% and coronary revascularization, by 19%.

The drug was also well tolerated in the mixed population of primary and secondary prevention patients unable or unwilling to take statins.

Mitchel L. Zoler/MDedge News

“These findings establish bempedoic acid as an effective approach to reduce major cardiovascular events in statin-intolerant patients,” study chair, Steven E. Nissen, MD, of the Cleveland Clinic concluded.

Dr. Nissen presented the CLEAR Outcomes trial at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.

The study was simultaneously published online in the New England Journal of Medicine. Top-line results were previously reported in December 2022.

Dr. Nissen pointed out that, while in the current study bempedoic acid was studied as monotherapy, he believes the drug will mainly be used in clinical practice in combination with ezetimibe, a combination shown to reduce LDL by 38%. “I think this is how it will be used in clinical practice. So, we can get an almost 40% LDL reduction – that’s about the same as 40 mg simvastatin or 20 mg atorvastatin – without giving a statin. And I think that’s where I see the potential of this therapy,” he said.

Dr. Nissen described statin intolerance as “a vexing problem” that prevents many patients from achieving LDL cholesterol levels associated with cardiovascular benefits.

He explained that bempedoic acid, an adenosine triphosphate citrate lyase inhibitor, inhibits hepatic cholesterol synthesis upstream of hydroxymethylglutaryl coenzyme A reductase, the enzyme inhibited by statins. Bempedoic acid is a prodrug activated in the liver, but not in peripheral tissues, resulting in a low incidence of muscle-related adverse events. Although bempedoic acid is approved for lowering LDL cholesterol, this is the first trial to assess its effects on cardiovascular outcomes.
 

CLEAR Outcomes

The CLEAR Outcomes trial included 13,970 patients (48% women) from 32 countries who were unable or unwilling to take statins owing to unacceptable adverse effects and who had, or were at high risk for, cardiovascular disease. They were randomly assigned to oral bempedoic acid, 180 mg daily, or placebo.

The mean LDL cholesterol level at baseline was 139 mg/dL in both groups, and after 6 months, the reduction in the level was greater with bempedoic acid than with placebo by 29.2 mg/dL (a 21.1% reduction).

The drug was also associated with a 22% reduction in high-sensitivity C-reactive protein.

After a median duration of follow-up of 40.6 months, the incidence of a primary endpoint (cardiovascular death, MI, stroke, or coronary revascularization) was significantly lower (by 13%) with bempedoic acid than with placebo (11.7% vs. 13.3%; hazard ratio, 0.87; P = .004).

The absolute risk reduction was 1.6 percentage points, and the number needed to treat for 40 months to prevent one event was 63.

The secondary composite endpoint of cardiovascular death/stroke/MI was reduced by 15% (8.2% vs. 9.5%; HR, 0.85; P = .006). Fatal or nonfatal MI was reduced by 23% (3.7% vs. 4.8%; HR, 0.77; P = .002), and coronary revascularization was reduced by 19% (6.2% vs. 7.6%; HR, 0.81; P = .001).

Bempedoic acid had no significant effects on fatal or nonfatal stroke, death from cardiovascular causes, and death from any cause.

Subgroup analysis showed similar results across all groups and no difference in treatment effect between men and women.

Adverse events were reported by 25% of patients in both groups, with adverse events leading to discontinuation reported by 10.8% of the bempedoic acid group and 10.4% of the placebo group.

Muscle disorders were reported in 15.0% of the bempedoic acid group versus 15.4% of the placebo group. And there was also no difference in new cases of diabetes (16.1% vs. 17.1%).

Bempedoic acid was associated with small increases in the incidence of gout (3.1% vs. 2.1%) and cholelithiasis (2.2% vs. 1.2%), and also small increases in serum creatinine, uric acid, and hepatic enzyme levels.

In the NEJM article, the authors pointed out that the concept of statin intolerance remains controversial. Some recent studies suggested that reported adverse effects represent an anticipation of harm, often described as the “nocebo” effect.

“Whether real or perceived, statin intolerance remains a vexing clinical problem that can prevent patients who are guideline eligible for statin treatment from reaching LDL cholesterol levels associated with clinical benefits. Accordingly, alternative nonstatin therapies are needed to manage the LDL cholesterol level in these patients,” they wrote.

“Management of patients unable or unwilling to take statins represents a challenging and frustrating clinical issue. Regardless whether this problem represents the ‘nocebo’ effect or actual intolerance, these high-risk patients need effective alternative therapies,” Dr. Nissen concluded. “The CLEAR Outcomes trial provides a sound rationale for use of bempedoic acid to reduce major adverse cardiovascular outcomes in patients intolerant to statins.”
 

‘Compelling findings’

Discussing the trial at the ACC late-breaking clinical trial session, Michelle O’Donoghue, MD, Brigham and Women’s Hospital, Boston, noted that this is the largest trial to date in statin-intolerant patients.

She pointed out that although the issue of statin intolerance remains controversial, adherence to statins is often not good, so this is an important patient population to study.

She said it was “quite remarkable” that 48% of the study were women, adding: “There is still much that we need to understand about why women appear to be less willing or able to tolerate statin therapy.” 

Dr. O’Donoghue concluded that the study showed “compelling findings,” and the event reduction was in line with what would be expected from the LDL cholesterol reduction, further supporting the LDL cholesterol hypothesis. 

She added: “Bempedoic acid is an important addition to our arsenal of nonstatin LDL-lowering therapies. And while it was overall well tolerated, it did not get a complete free pass, as there were some modest safety concerns.”

In an editorial accompanying the NEJM publication, John Alexander, MD, Duke Clinical Research Institute, Durham, N.C., wrote: “The compelling results of the CLEAR Outcomes trial will and should increase the use of bempedoic acid in patients with established atherosclerotic vascular disease and in those at high risk for vascular disease who are unable or unwilling to take statins.”

He warned, however, that it is premature to consider bempedoic acid as an alternative to statins. “Given the overwhelming evidence of the vascular benefits of statins, clinicians should continue their efforts to prescribe them at the maximum tolerated doses for appropriate patients, including those who may have discontinued statins because of presumed side effects.”.

Dr. Alexander also pointed out that although bempedoic acid also reduces the LDL cholesterol level in patients taking statins, the clinical benefits of bempedoic acid added to standard statin therapy are unknown. 

On the observation that bempedoic acid had no observed effect on mortality, he noted that “Many individual trials of statins have also not shown an effect of the agent on mortality; it was only through the meta-analysis of multiple clinical trials that the effects of statins on mortality became clear.”

“Bempedoic acid has now entered the list of evidence-based alternatives to statins for primary and secondary prevention in patients at high cardiovascular risk,” Dr. Alexander concluded. “The benefits of bempedoic acid are now clearer, and it is now our responsibility to translate this information into better primary and secondary prevention for more at-risk patients, who will, as a result, benefit from fewer cardiovascular events.”

In a second editorial, John F. Keaney Jr., MD, Brigham and Women’s Hospital, said the lack of a clear association between bempedoic acid and muscle disorders, new-onset diabetes, or worsening hyperglycemia is “welcome news” for statin-intolerant patients.

But he cautioned that “these data must be interpreted cautiously, because bempedoic acid, when combined with a statin, appears to enhance the occurrence of muscle symptoms. Moreover, bempedoic acid has its own reported side effects, including tendon rupture, increased uric acid levels, gout, and reduced glomerular filtration rate, which are not seen with statin use.”

In terms of drug interactions, Dr. Keaney noted that bempedoic acid can increase the circulating levels of simvastatin and pravastatin, so it should not be used in patients who are receiving these agents at doses above 20 mg and 40 mg, respectively. Similarly, bempedoic acid should not be used with fibrates other than fenofibrate because of concerns regarding cholelithiasis.

“Available data clearly indicate that bempedoic acid can be used as an adjunct to statin and nonstatin therapies (except as noted above) to produce an additional 16%-26% reduction in the LDL cholesterol level,” he added. “However, it is not yet clear to what extent adjunctive bempedoic acid will further reduce the risk of cardiovascular events.”

The CLEAR Outcomes trial was supported by Esperion Therapeutics. Dr. Nissen reported receiving grants from AbbVie, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Esperion, Novartis, and Silence Pharmaceuticals and consultancies with Amgen and Glenmark Pharmaceuticals.

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

NEW ORLEANS – In the first pivotal randomized, controlled trial of a transcatheter device for the repair of severe tricuspid regurgitation, a large reduction in valve dysfunction was associated with substantial improvement in quality of life (QOL) persisting out of 1 year of follow-up, according to results of the TRILUMINATE trial.

Based on the low procedural risks of the repair, the principal investigator, Paul Sorajja, MD, called the results “very clinically meaningful” as he presented the results at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.

Ted Bosworth/MDedge News

Conducted at 65 centers in the United States, Canada, and North America, TRILUMINATE evaluated a transcatheter end-to-end (TEER) repair performed with the TriClip G4 Delivery System (Abbott). The study included two cohorts, both of which will be followed for 5 years. One included patients with very severe tricuspid regurgitation enrolled in a single arm. Data on this cohort is expected later in 2023.

In the randomized portion of the study, 350 patients enrolled with severe tricuspid regurgitation underwent TEER with a clipping device and then were followed on the guideline-directed therapy (GDMT) for heart failure they were receiving at baseline. The control group was managed on GDMT alone.

The primary composite endpoint at 1 year was a composite of death from any cause and/or tricuspid valve surgery, hospitalization for heart failure, and quality of life as measured with the Kansas City Cardiomyopathy questionnaire (KCCQ).
 

Benefit driven by quality of life

For the primary endpoint, the win ratio, a statistical calculation of those who did relative to those who did not benefit, was 1.48, signifying a 48% advantage (P = .02). This was driven almost entirely by the KCCQ endpoint. There was no significant difference death and/or tricuspid valve surgery, which occurred in about 10% of both groups (P = .75) or heart failure hospitalization, which was occurred in slightly more patients randomized to repair (14.9% vs. 12.1%; P = .41).

For KCCQ, the mean increase at 1 year was 12.3 points in the repair group versus 0.6 points (P < .001) in the control group. With an increase of 5-10 points typically considered to be clinically meaningful, the advantage of repair over GDMT at the threshold of 15 points or greater was highly statistically significant (49.7% vs. 26.4%; P < .0001).

This advantage was attributed to control of regurgitation. The proportion achieving moderate or less regurgitation sustained at 1 year was 87% in the repair group versus 4.8% in the GDMT group (P < .0001).

When assessed independent of treatment, KCCQ benefits at 1 year increased in a stepwise fashion as severity of regurgitation was reduced, climbing from 2 points if there was no improvement to 6 points with one grade in improvement and then to 18 points with at least a two-grade improvement.

For regurgitation, “the repair was extremely effective,” said Dr. Sorajja of Allina Health Minneapolis Heart Institute at Abbott Northwestern Hospital, Minneapolis. He added that the degree of regurgitation control in the TRILUMINATE trial “is the highest ever reported.” With previous trials with other transcatheter devices in development, the improvement so far has been on the order of 70%-80%.

For enrollment in TRILUMINATE, patients were required to have at least an intermediate risk of morbidity or mortality from tricuspid valve surgery. Exclusion criteria included a left ventricular ejection fraction (LVEF) less than 20% and severe pulmonary hypertension.

More than 70% of patients had the highest (torrential) or second highest (massive) category of regurgitation on a five-level scale by echocardiography. Almost all the remaining were at the third level (severe).

Of those enrolled, the average age was roughly 78 years. About 55% were women. Nearly 60% were in New York Heart Association class III or IV heart failure and most had significant comorbidities, including hypertension (> 80%), atrial fibrillation (about 90%), and renal disease (35%). Patients with diabetes (16%), chronic obstructive pulmonary disease (10%), and liver disease (7.5%) were represented in lower numbers.
 

Surgery is not necessarily an option

All enrolled patients were considered to be at intermediate or greater risk for mortality with surgical replacement of the tricuspid valve, but Dr. Sorajja pointed out that surgery, which involves valve replacement, is not necessarily an alternative to valve repair. Even in fit patients, the high morbidity, mortality, and extended hospital stay associated with surgical valve replacement makes this procedure unattractive.

In this trial, most patients who underwent the transcatheter procedure were discharged within a day. The safety was excellent, Dr. Sorajja said. Only three patients (1.7%) had a major adverse event. This included two cases of new-onset renal failure and one cardiovascular death. There were no cases of endocarditis requiring surgery or any other type of nonelective cardiovascular surgery, including for any device-related issue.

In the sick population enrolled, Dr. Sorajja characterized the number of adverse events over 1 year as “very low.”

Ted Bosworth/MDedge News

These results are important, according to Kendra Grubb, MD, surgical director of the Structural Heart and Valve Center, Emory University, Atlanta. While she expressed surprise that there was no signal of benefit on hard endpoints at 1 year, she emphasized that “these patients feel terrible,” and they are frustrating to manage because surgery is often contraindicated or impractical.

“Finally, we have something for this group,” she said, noting that the mortality from valve replacement surgery even among patients who are fit enough for surgery to be considered is about 10%.

Ajay Kirtane, MD, director of the Cardiac Catheterization Laboratories at Columbia University, New York, was more circumspect. He agreed that the improvement in QOL was encouraging, but cautioned that QOL is a particularly soft outcome in a nonrandomized trial in which patients may feel better just knowing that there regurgitation has been controlled. He found the lack of benefit on hard outcomes not just surprising but “disappointing.”

Still, he agreed the improvement in QOL is potentially meaningful for a procedure that appears to be relatively safe.

Dr. Sorajja reported financial relationships with Boston Scientific, Edwards Lifesciences, Foldax. 4C Medical, Gore Medtronic, Phillips, Siemens, Shifamed, Vdyne, xDot, and Abbott Structural, which provided funding for this trial. Dr. Grubb reported financial relationships with Abbott Vascular, Ancora Heart, Bioventrix, Boston Scientific, Edwards Lifesciences, 4C Medical, JenaValve, and Medtronic. Dr. Kirtane reported financial relationships with Abbott Vascular, Amgen, Boston Scientific, Chiesi, Medtronic, Opsens, Phillips, ReCor, Regeneron, and Zoll.

NEW ORLEANS – In the first pivotal randomized, controlled trial of a transcatheter device for the repair of severe tricuspid regurgitation, a large reduction in valve dysfunction was associated with substantial improvement in quality of life (QOL) persisting out of 1 year of follow-up, according to results of the TRILUMINATE trial.

Based on the low procedural risks of the repair, the principal investigator, Paul Sorajja, MD, called the results “very clinically meaningful” as he presented the results at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.

Ted Bosworth/MDedge News

Conducted at 65 centers in the United States, Canada, and North America, TRILUMINATE evaluated a transcatheter end-to-end (TEER) repair performed with the TriClip G4 Delivery System (Abbott). The study included two cohorts, both of which will be followed for 5 years. One included patients with very severe tricuspid regurgitation enrolled in a single arm. Data on this cohort is expected later in 2023.

In the randomized portion of the study, 350 patients enrolled with severe tricuspid regurgitation underwent TEER with a clipping device and then were followed on the guideline-directed therapy (GDMT) for heart failure they were receiving at baseline. The control group was managed on GDMT alone.

The primary composite endpoint at 1 year was a composite of death from any cause and/or tricuspid valve surgery, hospitalization for heart failure, and quality of life as measured with the Kansas City Cardiomyopathy questionnaire (KCCQ).
 

Benefit driven by quality of life

For the primary endpoint, the win ratio, a statistical calculation of those who did relative to those who did not benefit, was 1.48, signifying a 48% advantage (P = .02). This was driven almost entirely by the KCCQ endpoint. There was no significant difference death and/or tricuspid valve surgery, which occurred in about 10% of both groups (P = .75) or heart failure hospitalization, which was occurred in slightly more patients randomized to repair (14.9% vs. 12.1%; P = .41).

For KCCQ, the mean increase at 1 year was 12.3 points in the repair group versus 0.6 points (P < .001) in the control group. With an increase of 5-10 points typically considered to be clinically meaningful, the advantage of repair over GDMT at the threshold of 15 points or greater was highly statistically significant (49.7% vs. 26.4%; P < .0001).

This advantage was attributed to control of regurgitation. The proportion achieving moderate or less regurgitation sustained at 1 year was 87% in the repair group versus 4.8% in the GDMT group (P < .0001).

When assessed independent of treatment, KCCQ benefits at 1 year increased in a stepwise fashion as severity of regurgitation was reduced, climbing from 2 points if there was no improvement to 6 points with one grade in improvement and then to 18 points with at least a two-grade improvement.

For regurgitation, “the repair was extremely effective,” said Dr. Sorajja of Allina Health Minneapolis Heart Institute at Abbott Northwestern Hospital, Minneapolis. He added that the degree of regurgitation control in the TRILUMINATE trial “is the highest ever reported.” With previous trials with other transcatheter devices in development, the improvement so far has been on the order of 70%-80%.

For enrollment in TRILUMINATE, patients were required to have at least an intermediate risk of morbidity or mortality from tricuspid valve surgery. Exclusion criteria included a left ventricular ejection fraction (LVEF) less than 20% and severe pulmonary hypertension.

More than 70% of patients had the highest (torrential) or second highest (massive) category of regurgitation on a five-level scale by echocardiography. Almost all the remaining were at the third level (severe).

Of those enrolled, the average age was roughly 78 years. About 55% were women. Nearly 60% were in New York Heart Association class III or IV heart failure and most had significant comorbidities, including hypertension (> 80%), atrial fibrillation (about 90%), and renal disease (35%). Patients with diabetes (16%), chronic obstructive pulmonary disease (10%), and liver disease (7.5%) were represented in lower numbers.
 

Surgery is not necessarily an option

All enrolled patients were considered to be at intermediate or greater risk for mortality with surgical replacement of the tricuspid valve, but Dr. Sorajja pointed out that surgery, which involves valve replacement, is not necessarily an alternative to valve repair. Even in fit patients, the high morbidity, mortality, and extended hospital stay associated with surgical valve replacement makes this procedure unattractive.

In this trial, most patients who underwent the transcatheter procedure were discharged within a day. The safety was excellent, Dr. Sorajja said. Only three patients (1.7%) had a major adverse event. This included two cases of new-onset renal failure and one cardiovascular death. There were no cases of endocarditis requiring surgery or any other type of nonelective cardiovascular surgery, including for any device-related issue.

In the sick population enrolled, Dr. Sorajja characterized the number of adverse events over 1 year as “very low.”

Ted Bosworth/MDedge News

These results are important, according to Kendra Grubb, MD, surgical director of the Structural Heart and Valve Center, Emory University, Atlanta. While she expressed surprise that there was no signal of benefit on hard endpoints at 1 year, she emphasized that “these patients feel terrible,” and they are frustrating to manage because surgery is often contraindicated or impractical.

“Finally, we have something for this group,” she said, noting that the mortality from valve replacement surgery even among patients who are fit enough for surgery to be considered is about 10%.

Ajay Kirtane, MD, director of the Cardiac Catheterization Laboratories at Columbia University, New York, was more circumspect. He agreed that the improvement in QOL was encouraging, but cautioned that QOL is a particularly soft outcome in a nonrandomized trial in which patients may feel better just knowing that there regurgitation has been controlled. He found the lack of benefit on hard outcomes not just surprising but “disappointing.”

Still, he agreed the improvement in QOL is potentially meaningful for a procedure that appears to be relatively safe.

Dr. Sorajja reported financial relationships with Boston Scientific, Edwards Lifesciences, Foldax. 4C Medical, Gore Medtronic, Phillips, Siemens, Shifamed, Vdyne, xDot, and Abbott Structural, which provided funding for this trial. Dr. Grubb reported financial relationships with Abbott Vascular, Ancora Heart, Bioventrix, Boston Scientific, Edwards Lifesciences, 4C Medical, JenaValve, and Medtronic. Dr. Kirtane reported financial relationships with Abbott Vascular, Amgen, Boston Scientific, Chiesi, Medtronic, Opsens, Phillips, ReCor, Regeneron, and Zoll.

NEW ORLEANS – In the first pivotal randomized, controlled trial of a transcatheter device for the repair of severe tricuspid regurgitation, a large reduction in valve dysfunction was associated with substantial improvement in quality of life (QOL) persisting out of 1 year of follow-up, according to results of the TRILUMINATE trial.

Based on the low procedural risks of the repair, the principal investigator, Paul Sorajja, MD, called the results “very clinically meaningful” as he presented the results at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.

Ted Bosworth/MDedge News

Conducted at 65 centers in the United States, Canada, and North America, TRILUMINATE evaluated a transcatheter end-to-end (TEER) repair performed with the TriClip G4 Delivery System (Abbott). The study included two cohorts, both of which will be followed for 5 years. One included patients with very severe tricuspid regurgitation enrolled in a single arm. Data on this cohort is expected later in 2023.

In the randomized portion of the study, 350 patients enrolled with severe tricuspid regurgitation underwent TEER with a clipping device and then were followed on the guideline-directed therapy (GDMT) for heart failure they were receiving at baseline. The control group was managed on GDMT alone.

The primary composite endpoint at 1 year was a composite of death from any cause and/or tricuspid valve surgery, hospitalization for heart failure, and quality of life as measured with the Kansas City Cardiomyopathy questionnaire (KCCQ).
 

Benefit driven by quality of life

For the primary endpoint, the win ratio, a statistical calculation of those who did relative to those who did not benefit, was 1.48, signifying a 48% advantage (P = .02). This was driven almost entirely by the KCCQ endpoint. There was no significant difference death and/or tricuspid valve surgery, which occurred in about 10% of both groups (P = .75) or heart failure hospitalization, which was occurred in slightly more patients randomized to repair (14.9% vs. 12.1%; P = .41).

For KCCQ, the mean increase at 1 year was 12.3 points in the repair group versus 0.6 points (P < .001) in the control group. With an increase of 5-10 points typically considered to be clinically meaningful, the advantage of repair over GDMT at the threshold of 15 points or greater was highly statistically significant (49.7% vs. 26.4%; P < .0001).

This advantage was attributed to control of regurgitation. The proportion achieving moderate or less regurgitation sustained at 1 year was 87% in the repair group versus 4.8% in the GDMT group (P < .0001).

When assessed independent of treatment, KCCQ benefits at 1 year increased in a stepwise fashion as severity of regurgitation was reduced, climbing from 2 points if there was no improvement to 6 points with one grade in improvement and then to 18 points with at least a two-grade improvement.

For regurgitation, “the repair was extremely effective,” said Dr. Sorajja of Allina Health Minneapolis Heart Institute at Abbott Northwestern Hospital, Minneapolis. He added that the degree of regurgitation control in the TRILUMINATE trial “is the highest ever reported.” With previous trials with other transcatheter devices in development, the improvement so far has been on the order of 70%-80%.

For enrollment in TRILUMINATE, patients were required to have at least an intermediate risk of morbidity or mortality from tricuspid valve surgery. Exclusion criteria included a left ventricular ejection fraction (LVEF) less than 20% and severe pulmonary hypertension.

More than 70% of patients had the highest (torrential) or second highest (massive) category of regurgitation on a five-level scale by echocardiography. Almost all the remaining were at the third level (severe).

Of those enrolled, the average age was roughly 78 years. About 55% were women. Nearly 60% were in New York Heart Association class III or IV heart failure and most had significant comorbidities, including hypertension (> 80%), atrial fibrillation (about 90%), and renal disease (35%). Patients with diabetes (16%), chronic obstructive pulmonary disease (10%), and liver disease (7.5%) were represented in lower numbers.
 

Surgery is not necessarily an option

All enrolled patients were considered to be at intermediate or greater risk for mortality with surgical replacement of the tricuspid valve, but Dr. Sorajja pointed out that surgery, which involves valve replacement, is not necessarily an alternative to valve repair. Even in fit patients, the high morbidity, mortality, and extended hospital stay associated with surgical valve replacement makes this procedure unattractive.

In this trial, most patients who underwent the transcatheter procedure were discharged within a day. The safety was excellent, Dr. Sorajja said. Only three patients (1.7%) had a major adverse event. This included two cases of new-onset renal failure and one cardiovascular death. There were no cases of endocarditis requiring surgery or any other type of nonelective cardiovascular surgery, including for any device-related issue.

In the sick population enrolled, Dr. Sorajja characterized the number of adverse events over 1 year as “very low.”

Ted Bosworth/MDedge News

These results are important, according to Kendra Grubb, MD, surgical director of the Structural Heart and Valve Center, Emory University, Atlanta. While she expressed surprise that there was no signal of benefit on hard endpoints at 1 year, she emphasized that “these patients feel terrible,” and they are frustrating to manage because surgery is often contraindicated or impractical.

“Finally, we have something for this group,” she said, noting that the mortality from valve replacement surgery even among patients who are fit enough for surgery to be considered is about 10%.

Ajay Kirtane, MD, director of the Cardiac Catheterization Laboratories at Columbia University, New York, was more circumspect. He agreed that the improvement in QOL was encouraging, but cautioned that QOL is a particularly soft outcome in a nonrandomized trial in which patients may feel better just knowing that there regurgitation has been controlled. He found the lack of benefit on hard outcomes not just surprising but “disappointing.”

Still, he agreed the improvement in QOL is potentially meaningful for a procedure that appears to be relatively safe.

Dr. Sorajja reported financial relationships with Boston Scientific, Edwards Lifesciences, Foldax. 4C Medical, Gore Medtronic, Phillips, Siemens, Shifamed, Vdyne, xDot, and Abbott Structural, which provided funding for this trial. Dr. Grubb reported financial relationships with Abbott Vascular, Ancora Heart, Bioventrix, Boston Scientific, Edwards Lifesciences, 4C Medical, JenaValve, and Medtronic. Dr. Kirtane reported financial relationships with Abbott Vascular, Amgen, Boston Scientific, Chiesi, Medtronic, Opsens, Phillips, ReCor, Regeneron, and Zoll.