Cardiology News

TOPLINE:

The metabolically unhealthy obesity phenotype, with its multiple comorbidities, may be the most practical group of people with obesity to screen for Cushing syndrome rather than all patients with obesity.

METHODOLOGY:

• Obesity is a key clinical feature of Cushing syndrome and shares many overlapping characteristics. An ongoing debate continues about the need to screen patients with obesity for the rare endocrine disease, but phenotypes known as metabolically healthy or unhealthy obesity may help better define an at-risk population.
• To assess the prevalence of Cushing syndrome by metabolic health status, researchers conducted a retrospective study of 1008 patients with obesity (mean age, 40 years; 83% women; body mass index ≥ 30) seen at an endocrinology outpatient clinic in Turkey between December 2020 and June 2022.
• They screened patients for Cushing syndrome with an overnight dexamethasone suppression test (1 mg DST), an oral dexamethasone dose given at 11 PM followed by a fasting blood sample for cortisol measurement the next morning. A serum cortisol level < 1.8 mcg/dL indicated normal suppression.
• Patients were categorized into those with metabolically healthy obesity (n = 229) or metabolically unhealthy obesity (n = 779) based on the absence or presence of comorbidities such as diabetes, prediabetes, coronary artery disease, hypertension, or dyslipidemia.

TAKEAWAY:

• The overall prevalence of Cushing syndrome in the study cohort was 0.2%, with only two patients definitively diagnosed after more tests and the remaining 10 classified as having subclinical hypercortisolism.
• Cortisol levels following the 1 mg DST were higher in the metabolically unhealthy obesity group than in the metabolically healthy obesity group (P = .001).
• Among the 12 patients with unsuppressed levels of cortisol, 11 belonged to the metabolically unhealthy obesity group, indicating a strong association between metabolic health and the levels of cortisol.
• The test demonstrated a specificity of 99% and sensitivity of 100% for screening Cushing syndrome in patients with obesity.

IN PRACTICE:

“Screening all patients with obesity for CS [Cushing syndrome] without considering any associated metabolic conditions appears impractical and unnecessary in everyday clinical practice,” the authors wrote. “However, it may be more reasonable and applicable to selectively screen the patients with obesity having comorbidities such as DM [diabetes mellitus], hypertension, dyslipidemia, or coronary artery disease, which lead to a metabolically unhealthy phenotype, rather than all individuals with obesity,” they added.

SOURCE:

The study, led by Sema Hepsen, Ankara Etlik City Hospital, Department of Endocrinology and Metabolism, Ankara, Turkey, was published online in the International Journal of Obesity.

LIMITATIONS:

The single-center design of the study and inclusion of patients from a single racial group may limit the generalizability of the findings. The retrospective design prevented the retrieval of all relevant data on clinical features and fat distribution.

DISCLOSURES:

The study was supported by an open access funding provided by the Scientific and Technological Research Council of Türkiye. The authors declared no conflicts of interest.

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

TOPLINE:

The metabolically unhealthy obesity phenotype, with its multiple comorbidities, may be the most practical group of people with obesity to screen for Cushing syndrome rather than all patients with obesity.

METHODOLOGY:

• Obesity is a key clinical feature of Cushing syndrome and shares many overlapping characteristics. An ongoing debate continues about the need to screen patients with obesity for the rare endocrine disease, but phenotypes known as metabolically healthy or unhealthy obesity may help better define an at-risk population.
• To assess the prevalence of Cushing syndrome by metabolic health status, researchers conducted a retrospective study of 1008 patients with obesity (mean age, 40 years; 83% women; body mass index ≥ 30) seen at an endocrinology outpatient clinic in Turkey between December 2020 and June 2022.
• They screened patients for Cushing syndrome with an overnight dexamethasone suppression test (1 mg DST), an oral dexamethasone dose given at 11 PM followed by a fasting blood sample for cortisol measurement the next morning. A serum cortisol level < 1.8 mcg/dL indicated normal suppression.
• Patients were categorized into those with metabolically healthy obesity (n = 229) or metabolically unhealthy obesity (n = 779) based on the absence or presence of comorbidities such as diabetes, prediabetes, coronary artery disease, hypertension, or dyslipidemia.

TAKEAWAY:

• The overall prevalence of Cushing syndrome in the study cohort was 0.2%, with only two patients definitively diagnosed after more tests and the remaining 10 classified as having subclinical hypercortisolism.
• Cortisol levels following the 1 mg DST were higher in the metabolically unhealthy obesity group than in the metabolically healthy obesity group (P = .001).
• Among the 12 patients with unsuppressed levels of cortisol, 11 belonged to the metabolically unhealthy obesity group, indicating a strong association between metabolic health and the levels of cortisol.
• The test demonstrated a specificity of 99% and sensitivity of 100% for screening Cushing syndrome in patients with obesity.

IN PRACTICE:

“Screening all patients with obesity for CS [Cushing syndrome] without considering any associated metabolic conditions appears impractical and unnecessary in everyday clinical practice,” the authors wrote. “However, it may be more reasonable and applicable to selectively screen the patients with obesity having comorbidities such as DM [diabetes mellitus], hypertension, dyslipidemia, or coronary artery disease, which lead to a metabolically unhealthy phenotype, rather than all individuals with obesity,” they added.

SOURCE:

The study, led by Sema Hepsen, Ankara Etlik City Hospital, Department of Endocrinology and Metabolism, Ankara, Turkey, was published online in the International Journal of Obesity.

LIMITATIONS:

The single-center design of the study and inclusion of patients from a single racial group may limit the generalizability of the findings. The retrospective design prevented the retrieval of all relevant data on clinical features and fat distribution.

DISCLOSURES:

The study was supported by an open access funding provided by the Scientific and Technological Research Council of Türkiye. The authors declared no conflicts of interest.

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

TOPLINE:

The metabolically unhealthy obesity phenotype, with its multiple comorbidities, may be the most practical group of people with obesity to screen for Cushing syndrome rather than all patients with obesity.

METHODOLOGY:

• Obesity is a key clinical feature of Cushing syndrome and shares many overlapping characteristics. An ongoing debate continues about the need to screen patients with obesity for the rare endocrine disease, but phenotypes known as metabolically healthy or unhealthy obesity may help better define an at-risk population.
• To assess the prevalence of Cushing syndrome by metabolic health status, researchers conducted a retrospective study of 1008 patients with obesity (mean age, 40 years; 83% women; body mass index ≥ 30) seen at an endocrinology outpatient clinic in Turkey between December 2020 and June 2022.
• They screened patients for Cushing syndrome with an overnight dexamethasone suppression test (1 mg DST), an oral dexamethasone dose given at 11 PM followed by a fasting blood sample for cortisol measurement the next morning. A serum cortisol level < 1.8 mcg/dL indicated normal suppression.
• Patients were categorized into those with metabolically healthy obesity (n = 229) or metabolically unhealthy obesity (n = 779) based on the absence or presence of comorbidities such as diabetes, prediabetes, coronary artery disease, hypertension, or dyslipidemia.

TAKEAWAY:

• The overall prevalence of Cushing syndrome in the study cohort was 0.2%, with only two patients definitively diagnosed after more tests and the remaining 10 classified as having subclinical hypercortisolism.
• Cortisol levels following the 1 mg DST were higher in the metabolically unhealthy obesity group than in the metabolically healthy obesity group (P = .001).
• Among the 12 patients with unsuppressed levels of cortisol, 11 belonged to the metabolically unhealthy obesity group, indicating a strong association between metabolic health and the levels of cortisol.
• The test demonstrated a specificity of 99% and sensitivity of 100% for screening Cushing syndrome in patients with obesity.

IN PRACTICE:

“Screening all patients with obesity for CS [Cushing syndrome] without considering any associated metabolic conditions appears impractical and unnecessary in everyday clinical practice,” the authors wrote. “However, it may be more reasonable and applicable to selectively screen the patients with obesity having comorbidities such as DM [diabetes mellitus], hypertension, dyslipidemia, or coronary artery disease, which lead to a metabolically unhealthy phenotype, rather than all individuals with obesity,” they added.

SOURCE:

The study, led by Sema Hepsen, Ankara Etlik City Hospital, Department of Endocrinology and Metabolism, Ankara, Turkey, was published online in the International Journal of Obesity.

LIMITATIONS:

The single-center design of the study and inclusion of patients from a single racial group may limit the generalizability of the findings. The retrospective design prevented the retrieval of all relevant data on clinical features and fat distribution.

DISCLOSURES:

The study was supported by an open access funding provided by the Scientific and Technological Research Council of Türkiye. The authors declared no conflicts of interest.

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

Using a cell phone for at least one call per week is linked to a higher risk for cardiovascular disease (CVD), especially among smokers and patients with diabetes, according to a new UK Biobank analysis.

“We found that a poor sleep pattern, psychological distress, and neuroticism significantly mediated the positive association between weekly mobile phone usage time and the risk for incident CVD, with a mediating proportion of 5.11%, 11.50%, and 2.25%, respectively,” said principal investigator Xianhui Qin, MD, professor of nephrology at Southern Medical University, Guangzhou, China.

Poor sleep patterns and poor mental health could disrupt circadian rhythms and endocrine and metabolic functions, as well as increase inflammation, he explained.

In addition, chronic exposure to radiofrequency electromagnetic fields (RF-EMF) emitted from cell phones could lead to oxidative stress and an inflammatory response. Combined with smoking and diabetes, this exposure “may have a synergistic effect in increasing CVD risk,” Dr. Qin suggested.

The study was published online in the Canadian Journal of Cardiology.
 

Risk Underestimated?

The researchers aimed to examine the association of regular cell phone use with incident CVD and explore the mediating effects of sleep and mental health using linked hospital and mortality records.

Their analysis included 444,027 participants (mean age, 56 years; 44% men) without a history of CVD from the UK Biobank. A total of 378,161 participants were regular cell phone users.

Regular cell phone use was defined as at least one call per week. Weekly use was self-reported as the average time of calls per week during the previous 3 months.

The primary outcome was incident CVD. Secondary outcomes were each component of CVD (ie, coronary heart disease, stroke, atrial fibrillation, and heart failure) and increased carotid intima media thickness (CIMT).

Compared with nonregular cell phone users, regular users were younger, had higher proportions of current smokers and urban residents, and had lower proportions of history of hypertension and diabetes. They also had higher income, Townsend deprivation index, and body mass index, and lower education levels.

During a median follow-up of 12.3 years, 56,181 participants developed incident CVD. Compared with nonregular cell phone users, regular users had a significantly higher risk for incident CVD (hazard ratio, 1.04) and increased CIMT (odds ratio, 1.11).

Among regular cell phone users, the duration of cell phone use and hands-free device/speakerphone use during calls was not significantly associated with incident CVD. Yet a significant and positive dose-response relationship was seen between weekly cell phone usage time and the risk for CVD. The positive association was stronger in current vs noncurrent smokers and people with vs without diabetes.

To different extents, sleep patterns (5.11%), psychologic distress (11.5%), and neuroticism (2.25%) mediated the relationship between weekly cell phone usage time and the risk for incident CVD.

“Our study suggests that despite the advantages of mobile phone use, we should also pay attention to the potential harm of mobile phone use to cardiovascular health,” Dr. Qin said. “Future studies to assess the risk-benefit balance will help promote mobile phone use patterns that are conducive to cardiovascular health.”

Meanwhile, he added, “We encourage measures to reduce time spent on mobile phones to promote the primary prevention of CVD. On the other hand, improving sleep and mental health status may help reduce the higher risk of CVD associated with mobile phone use.”

There are several limitations to the study in addition to its observational nature, which cannot show cause and effect. The questionnaires on cell phone use were restricted to phone calls; other use patterns of cell phones (eg, messaging, watching videos, and browsing the web) were not considered. Although the researchers adjusted for many potential confounders, unmeasured confounding bias (eg, the type of cell phone used and other sources of RF-EMF) cannot be eliminated.
 

Weak Link?

In a comment, Nicholas Grubic, MSc, a PhD student in epidemiology at the University of Toronto, Ontario, Canada, and coauthor of a related editorial, said, “I found it interesting that there was a connection observed between mobile phone use and CVD. However, it is crucial to understand that this link appeared to be much weaker compared with other well-known cardiovascular risk factors, such as smoking, diabetes, and high blood pressure. For now, mobile phone use should not be a major concern for most people.”

Nevertheless, clinicians should encourage patients to practice healthy habits around their screen time, he advised. “This could include limiting mobile phone use before bedtime and taking regular breaks to engage in activities that promote heart health, such as exercising or spending time outdoors.

“For the time being, we probably won’t see mobile phone use included in standard assessments for cardiovascular risk or as a focal point of cardiovascular health promotion initiatives,” he added. Instead, clinicians should “focus on established risk factors that have a stronger impact on patients’ cardiovascular health.”

Nieca Goldberg, MD, a clinical associate professor of medicine at NYU Grossman School of Medicine in New York City and American Heart Association volunteer expert, had a similar message. “You don’t have to go back to using a landline,” she said. “Instead, patients should be more mindful of how much phone use is taking away from their physical activity, keeping them from sleeping, and causing them stress.” Clinicians should also remember to counsel smokers on smoking cessation.

“It would be important for future studies to look at time spent on the phone and the type of activities patients are doing on their phones, such as social media, calls, texts, movies, or streaming TV shows,” she said. “It would be important to see how phone use is leading to a sedentary lifestyle” and what that means for a larger, more diverse population.

The study was supported by the National Key R&D Program, the National Natural Science Foundation of China, and the Outstanding Youth Development Scheme of Nanfang Hospital, Southern Medical University. Dr. Qin, Dr. Grubic, and Dr. Goldberg reported having no relevant financial relationships.

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

Using a cell phone for at least one call per week is linked to a higher risk for cardiovascular disease (CVD), especially among smokers and patients with diabetes, according to a new UK Biobank analysis.

“We found that a poor sleep pattern, psychological distress, and neuroticism significantly mediated the positive association between weekly mobile phone usage time and the risk for incident CVD, with a mediating proportion of 5.11%, 11.50%, and 2.25%, respectively,” said principal investigator Xianhui Qin, MD, professor of nephrology at Southern Medical University, Guangzhou, China.

Poor sleep patterns and poor mental health could disrupt circadian rhythms and endocrine and metabolic functions, as well as increase inflammation, he explained.

In addition, chronic exposure to radiofrequency electromagnetic fields (RF-EMF) emitted from cell phones could lead to oxidative stress and an inflammatory response. Combined with smoking and diabetes, this exposure “may have a synergistic effect in increasing CVD risk,” Dr. Qin suggested.

The study was published online in the Canadian Journal of Cardiology.
 

Risk Underestimated?

The researchers aimed to examine the association of regular cell phone use with incident CVD and explore the mediating effects of sleep and mental health using linked hospital and mortality records.

Their analysis included 444,027 participants (mean age, 56 years; 44% men) without a history of CVD from the UK Biobank. A total of 378,161 participants were regular cell phone users.

Regular cell phone use was defined as at least one call per week. Weekly use was self-reported as the average time of calls per week during the previous 3 months.

The primary outcome was incident CVD. Secondary outcomes were each component of CVD (ie, coronary heart disease, stroke, atrial fibrillation, and heart failure) and increased carotid intima media thickness (CIMT).

Compared with nonregular cell phone users, regular users were younger, had higher proportions of current smokers and urban residents, and had lower proportions of history of hypertension and diabetes. They also had higher income, Townsend deprivation index, and body mass index, and lower education levels.

During a median follow-up of 12.3 years, 56,181 participants developed incident CVD. Compared with nonregular cell phone users, regular users had a significantly higher risk for incident CVD (hazard ratio, 1.04) and increased CIMT (odds ratio, 1.11).

Among regular cell phone users, the duration of cell phone use and hands-free device/speakerphone use during calls was not significantly associated with incident CVD. Yet a significant and positive dose-response relationship was seen between weekly cell phone usage time and the risk for CVD. The positive association was stronger in current vs noncurrent smokers and people with vs without diabetes.

To different extents, sleep patterns (5.11%), psychologic distress (11.5%), and neuroticism (2.25%) mediated the relationship between weekly cell phone usage time and the risk for incident CVD.

“Our study suggests that despite the advantages of mobile phone use, we should also pay attention to the potential harm of mobile phone use to cardiovascular health,” Dr. Qin said. “Future studies to assess the risk-benefit balance will help promote mobile phone use patterns that are conducive to cardiovascular health.”

Meanwhile, he added, “We encourage measures to reduce time spent on mobile phones to promote the primary prevention of CVD. On the other hand, improving sleep and mental health status may help reduce the higher risk of CVD associated with mobile phone use.”

There are several limitations to the study in addition to its observational nature, which cannot show cause and effect. The questionnaires on cell phone use were restricted to phone calls; other use patterns of cell phones (eg, messaging, watching videos, and browsing the web) were not considered. Although the researchers adjusted for many potential confounders, unmeasured confounding bias (eg, the type of cell phone used and other sources of RF-EMF) cannot be eliminated.
 

Weak Link?

In a comment, Nicholas Grubic, MSc, a PhD student in epidemiology at the University of Toronto, Ontario, Canada, and coauthor of a related editorial, said, “I found it interesting that there was a connection observed between mobile phone use and CVD. However, it is crucial to understand that this link appeared to be much weaker compared with other well-known cardiovascular risk factors, such as smoking, diabetes, and high blood pressure. For now, mobile phone use should not be a major concern for most people.”

Nevertheless, clinicians should encourage patients to practice healthy habits around their screen time, he advised. “This could include limiting mobile phone use before bedtime and taking regular breaks to engage in activities that promote heart health, such as exercising or spending time outdoors.

“For the time being, we probably won’t see mobile phone use included in standard assessments for cardiovascular risk or as a focal point of cardiovascular health promotion initiatives,” he added. Instead, clinicians should “focus on established risk factors that have a stronger impact on patients’ cardiovascular health.”

Nieca Goldberg, MD, a clinical associate professor of medicine at NYU Grossman School of Medicine in New York City and American Heart Association volunteer expert, had a similar message. “You don’t have to go back to using a landline,” she said. “Instead, patients should be more mindful of how much phone use is taking away from their physical activity, keeping them from sleeping, and causing them stress.” Clinicians should also remember to counsel smokers on smoking cessation.

“It would be important for future studies to look at time spent on the phone and the type of activities patients are doing on their phones, such as social media, calls, texts, movies, or streaming TV shows,” she said. “It would be important to see how phone use is leading to a sedentary lifestyle” and what that means for a larger, more diverse population.

The study was supported by the National Key R&D Program, the National Natural Science Foundation of China, and the Outstanding Youth Development Scheme of Nanfang Hospital, Southern Medical University. Dr. Qin, Dr. Grubic, and Dr. Goldberg reported having no relevant financial relationships.

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

Using a cell phone for at least one call per week is linked to a higher risk for cardiovascular disease (CVD), especially among smokers and patients with diabetes, according to a new UK Biobank analysis.

“We found that a poor sleep pattern, psychological distress, and neuroticism significantly mediated the positive association between weekly mobile phone usage time and the risk for incident CVD, with a mediating proportion of 5.11%, 11.50%, and 2.25%, respectively,” said principal investigator Xianhui Qin, MD, professor of nephrology at Southern Medical University, Guangzhou, China.

Poor sleep patterns and poor mental health could disrupt circadian rhythms and endocrine and metabolic functions, as well as increase inflammation, he explained.

In addition, chronic exposure to radiofrequency electromagnetic fields (RF-EMF) emitted from cell phones could lead to oxidative stress and an inflammatory response. Combined with smoking and diabetes, this exposure “may have a synergistic effect in increasing CVD risk,” Dr. Qin suggested.

The study was published online in the Canadian Journal of Cardiology.
 

Risk Underestimated?

The researchers aimed to examine the association of regular cell phone use with incident CVD and explore the mediating effects of sleep and mental health using linked hospital and mortality records.

Their analysis included 444,027 participants (mean age, 56 years; 44% men) without a history of CVD from the UK Biobank. A total of 378,161 participants were regular cell phone users.

Regular cell phone use was defined as at least one call per week. Weekly use was self-reported as the average time of calls per week during the previous 3 months.

The primary outcome was incident CVD. Secondary outcomes were each component of CVD (ie, coronary heart disease, stroke, atrial fibrillation, and heart failure) and increased carotid intima media thickness (CIMT).

Compared with nonregular cell phone users, regular users were younger, had higher proportions of current smokers and urban residents, and had lower proportions of history of hypertension and diabetes. They also had higher income, Townsend deprivation index, and body mass index, and lower education levels.

During a median follow-up of 12.3 years, 56,181 participants developed incident CVD. Compared with nonregular cell phone users, regular users had a significantly higher risk for incident CVD (hazard ratio, 1.04) and increased CIMT (odds ratio, 1.11).

Among regular cell phone users, the duration of cell phone use and hands-free device/speakerphone use during calls was not significantly associated with incident CVD. Yet a significant and positive dose-response relationship was seen between weekly cell phone usage time and the risk for CVD. The positive association was stronger in current vs noncurrent smokers and people with vs without diabetes.

To different extents, sleep patterns (5.11%), psychologic distress (11.5%), and neuroticism (2.25%) mediated the relationship between weekly cell phone usage time and the risk for incident CVD.

“Our study suggests that despite the advantages of mobile phone use, we should also pay attention to the potential harm of mobile phone use to cardiovascular health,” Dr. Qin said. “Future studies to assess the risk-benefit balance will help promote mobile phone use patterns that are conducive to cardiovascular health.”

Meanwhile, he added, “We encourage measures to reduce time spent on mobile phones to promote the primary prevention of CVD. On the other hand, improving sleep and mental health status may help reduce the higher risk of CVD associated with mobile phone use.”

There are several limitations to the study in addition to its observational nature, which cannot show cause and effect. The questionnaires on cell phone use were restricted to phone calls; other use patterns of cell phones (eg, messaging, watching videos, and browsing the web) were not considered. Although the researchers adjusted for many potential confounders, unmeasured confounding bias (eg, the type of cell phone used and other sources of RF-EMF) cannot be eliminated.
 

Weak Link?

In a comment, Nicholas Grubic, MSc, a PhD student in epidemiology at the University of Toronto, Ontario, Canada, and coauthor of a related editorial, said, “I found it interesting that there was a connection observed between mobile phone use and CVD. However, it is crucial to understand that this link appeared to be much weaker compared with other well-known cardiovascular risk factors, such as smoking, diabetes, and high blood pressure. For now, mobile phone use should not be a major concern for most people.”

Nevertheless, clinicians should encourage patients to practice healthy habits around their screen time, he advised. “This could include limiting mobile phone use before bedtime and taking regular breaks to engage in activities that promote heart health, such as exercising or spending time outdoors.

“For the time being, we probably won’t see mobile phone use included in standard assessments for cardiovascular risk or as a focal point of cardiovascular health promotion initiatives,” he added. Instead, clinicians should “focus on established risk factors that have a stronger impact on patients’ cardiovascular health.”

Nieca Goldberg, MD, a clinical associate professor of medicine at NYU Grossman School of Medicine in New York City and American Heart Association volunteer expert, had a similar message. “You don’t have to go back to using a landline,” she said. “Instead, patients should be more mindful of how much phone use is taking away from their physical activity, keeping them from sleeping, and causing them stress.” Clinicians should also remember to counsel smokers on smoking cessation.

“It would be important for future studies to look at time spent on the phone and the type of activities patients are doing on their phones, such as social media, calls, texts, movies, or streaming TV shows,” she said. “It would be important to see how phone use is leading to a sedentary lifestyle” and what that means for a larger, more diverse population.

The study was supported by the National Key R&D Program, the National Natural Science Foundation of China, and the Outstanding Youth Development Scheme of Nanfang Hospital, Southern Medical University. Dr. Qin, Dr. Grubic, and Dr. Goldberg reported having no relevant financial relationships.

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

A so-called “oatzempic” diet has been bouncing around the internet posing as a cheap — and available — weight loss alternative to Ozempic.

Fans of the diet, made trendy by TikTok postings and a clever name, claim that an oat-based smoothie helps people quickly shed lots of weight. The smoothie is made by blending 1/2 cup of oats, 1 cup of water, a squeeze of lime, and maybe a dash of cinnamon or other flavoring agents, typically as the first meal of the day, often after fasting, followed by normal meals.

Despite the hype, the oatzempic drink is a far cry from Ozempic (semaglutide), the glucagon-like peptide 1 (GLP-1) medication the Food and Drug Administration has approved only for type 2 diabetes management but used off label for weight loss.

So how do pulverized oats stack up against prescription-based GLP-1s? According to two nutrition experts, they’re not as effective as some TikTok influencers claim. And in people with diabetes, the diet can be dangerous.
 

Nutritionists Answer Questions on Oatzempic

Caroline West Passerrello, EdD, RDN, LDN, an instructor and community coordinator in the School of Health and Rehabilitation Sciences at the University of Pittsburgh, Pennsylvania, and Emma Laing, PhD, RDN, LD, a clinical professor and director of dietetics in the College of Family and Consumer Sciences at the University of Georgia, Athens, talked about this fad in emails.

Can the ‘oatzempic’ diet help people lose weight?

Dr. Passerrello: Oats are particularly high in soluble fiber, and high-fiber foods can increase the natural production of GLPs. But studies are mixed on whether this happens when eating oats.

The high content of soluble beta-glucan fiber in oats and the appetite-suppressing citric acid in lime can potentially promote decreased appetite and increased satiety. But a bowl of oatmeal, though not as trendy, will probably produce the same results.

Is the oatzempic diet safe for people with type 2 diabetes?

Dr. Laing: This diet has the potential to cause harm. The diet and the drug are not similar in mechanism of action or strength of scientific evidence to support their role in diabetes and weight management. There is no evidence that this concoction provides the same outcomes as GLP-1 agonists. Rapid weight loss is unsustainable and can be harmful, and frequent spikes in blood sugar can harm adults and children with diabetes. So the oatzempic diet’s safety depends on the rate of weight loss and the effect on blood sugar. While it provides beta-glucan from oats and citric acid from lime juice, it is missing protein, healthy fats, and other vitamins and minerals that enhance the nutrient content and stabilize blood sugar.

Maintaining relatively consistent, normal-range blood glucose concentrations is key for managing diabetes and lowering the risks for other health complications. Carbohydrate sources consumed on their own can produce greater blood sugar fluctuations than when combined with proteins and fats, which slow carbohydrate digestion speed. So pairing oats with fruits, vegetables, healthy fats, and protein sources enhances the flavor, texture, and nutrient composition of the dish and can help slow the postprandial rise in blood glucose.

In the long term, any restrictive fad diet likely cannot be sustained and increases the risk for malnutrition, metabolic rate slowing to conserve energy, depression, social isolation, or eating disorder.

Additional considerations apply to children, with or without diabetes. Restrictive, extreme diets that promise quick results typically “work” by promoting body water and muscle mass losses. Such diets are not only contraindicated in children, who are undergoing rapid growth and development, but also unsustainable and can lead to physical and psychological problems that carry into adulthood.

What strategies and tactics can physicians use to effectively communicate with their patients about safe and effective diets?

Dr. Laing: Encourage patients to be skeptical of social media trends that seem too good to be true. Many [social media] creators lack the education or professional credentials to offer sound nutrition advice, and their posts could do harm. Explain that individual nutrition needs differ considerably based on age, activity patterns, health conditions, and medications, and one person’s way of eating or success is often not realistic for someone else.

Encourage open dialogue and provide nonjudgmental advice. If the taste of oatzempic intrigues patients, there is likely no harm in experimenting. Work on ensuring their meals are adequate in calories and contain sources of protein and healthy fats to prevent spikes in blood glucose. It’s crucial to communicate that weight loss doesn’t always equate with improved health.

Sharing information from the Academy of Nutrition and Dietetics and the American Diabetes Association can equip patients with tools they can implement under their clinician’s guidance. A provider’s greatest ally in diabetes care is a registered dietitian nutritionist (RDN) who is a Certified Diabetes Care and Education Specialist. RDNs will determine specific energy and nutrient needs and provide medical nutrition therapy such as carbohydrate counting, simplified meal plans, healthy food choices, exchange lists, and behavior strategies to help patients manage their diabetes. Many insurance plans cover these services.

What additional comments would you like to share with clinicians whose patients may ask them about the oatzempic diet?

Dr. Passerrello: What we do consistently matters. If your patient likes the taste of oatzempic in one meal a day, it’s a way to get more oats into their diet, if they focus their other meals on vegetables, fruits, whole grains, lean protein, and unsaturated fats.

Diets are out, and sustainable dietary patterns are in. Diets are one-size-fits-all, whereas a sustainable dietary pattern is individualized based on a person’s goals, medical history, taste preferences, budget, and lifestyle. Visit MyPlate.gov or work with an RDN [visit https://www.eatright.org/find-a-nutrition-expert to find nutritionists near your patients] to determine what a sustainable dietary pattern looks like.

What do clinicians need to know about claims on social media that a related drink — ‘ricezempic’ — aids weight loss?

Dr. Laing: Ricezempic promoters claim that drinking the beverage — typically made by soaking 1/2 cup of uncooked white rice in 1 cup of water and the juice from half a lime, then discarding the rice and drinking the liquid before breakfast — will lead to weight loss because the strained water provides a small dose of resistant starch, which is a source of prebiotics. Studies have shown that ingesting prebiotics may help lower blood cholesterol, improve blood glucose and insulin sensitivity, and benefit digestive function; however, more research is needed to determine specifics and if prebiotics are proven for weight loss.

Does ricezempic work?

Dr. Laing: There is no evidence that this concoction provides the same outcomes as GLP-1 agonists. The diet and the drug are not similar in mechanism of action or strength of scientific evidence to support their role in diabetes and weight management. Even if ricezempic provides a small amount of resistant starch and hydration from the rice water and citric acid from the lime juice, it is missing fiber, protein, healthy fats, and other vitamins and minerals that enhance the nutrient content of a meal or snack and stabilize blood sugar.

What advice do you have for clinicians whose patients with diabetes ask them about ricezempic?

Dr. Laing: I would not suggest that patients rely on ricezempic to support their health. There is no scientific evidence to show that people will lose weight in the short or long term by drinking ricezempic before a meal (or as a meal replacement).

If your patients are aiming to increase their intake of prebiotics, they are naturally found in various vegetables, fruits, whole grains, and seeds and in yogurt and high-fiber breads and cereals. A nutritious eating pattern that includes these foods is most beneficial for health.

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

A so-called “oatzempic” diet has been bouncing around the internet posing as a cheap — and available — weight loss alternative to Ozempic.

Fans of the diet, made trendy by TikTok postings and a clever name, claim that an oat-based smoothie helps people quickly shed lots of weight. The smoothie is made by blending 1/2 cup of oats, 1 cup of water, a squeeze of lime, and maybe a dash of cinnamon or other flavoring agents, typically as the first meal of the day, often after fasting, followed by normal meals.

Despite the hype, the oatzempic drink is a far cry from Ozempic (semaglutide), the glucagon-like peptide 1 (GLP-1) medication the Food and Drug Administration has approved only for type 2 diabetes management but used off label for weight loss.

So how do pulverized oats stack up against prescription-based GLP-1s? According to two nutrition experts, they’re not as effective as some TikTok influencers claim. And in people with diabetes, the diet can be dangerous.
 

Nutritionists Answer Questions on Oatzempic

Caroline West Passerrello, EdD, RDN, LDN, an instructor and community coordinator in the School of Health and Rehabilitation Sciences at the University of Pittsburgh, Pennsylvania, and Emma Laing, PhD, RDN, LD, a clinical professor and director of dietetics in the College of Family and Consumer Sciences at the University of Georgia, Athens, talked about this fad in emails.

Can the ‘oatzempic’ diet help people lose weight?

Dr. Passerrello: Oats are particularly high in soluble fiber, and high-fiber foods can increase the natural production of GLPs. But studies are mixed on whether this happens when eating oats.

The high content of soluble beta-glucan fiber in oats and the appetite-suppressing citric acid in lime can potentially promote decreased appetite and increased satiety. But a bowl of oatmeal, though not as trendy, will probably produce the same results.

Is the oatzempic diet safe for people with type 2 diabetes?

Dr. Laing: This diet has the potential to cause harm. The diet and the drug are not similar in mechanism of action or strength of scientific evidence to support their role in diabetes and weight management. There is no evidence that this concoction provides the same outcomes as GLP-1 agonists. Rapid weight loss is unsustainable and can be harmful, and frequent spikes in blood sugar can harm adults and children with diabetes. So the oatzempic diet’s safety depends on the rate of weight loss and the effect on blood sugar. While it provides beta-glucan from oats and citric acid from lime juice, it is missing protein, healthy fats, and other vitamins and minerals that enhance the nutrient content and stabilize blood sugar.

Maintaining relatively consistent, normal-range blood glucose concentrations is key for managing diabetes and lowering the risks for other health complications. Carbohydrate sources consumed on their own can produce greater blood sugar fluctuations than when combined with proteins and fats, which slow carbohydrate digestion speed. So pairing oats with fruits, vegetables, healthy fats, and protein sources enhances the flavor, texture, and nutrient composition of the dish and can help slow the postprandial rise in blood glucose.

In the long term, any restrictive fad diet likely cannot be sustained and increases the risk for malnutrition, metabolic rate slowing to conserve energy, depression, social isolation, or eating disorder.

Additional considerations apply to children, with or without diabetes. Restrictive, extreme diets that promise quick results typically “work” by promoting body water and muscle mass losses. Such diets are not only contraindicated in children, who are undergoing rapid growth and development, but also unsustainable and can lead to physical and psychological problems that carry into adulthood.

What strategies and tactics can physicians use to effectively communicate with their patients about safe and effective diets?

Dr. Laing: Encourage patients to be skeptical of social media trends that seem too good to be true. Many [social media] creators lack the education or professional credentials to offer sound nutrition advice, and their posts could do harm. Explain that individual nutrition needs differ considerably based on age, activity patterns, health conditions, and medications, and one person’s way of eating or success is often not realistic for someone else.

Encourage open dialogue and provide nonjudgmental advice. If the taste of oatzempic intrigues patients, there is likely no harm in experimenting. Work on ensuring their meals are adequate in calories and contain sources of protein and healthy fats to prevent spikes in blood glucose. It’s crucial to communicate that weight loss doesn’t always equate with improved health.

Sharing information from the Academy of Nutrition and Dietetics and the American Diabetes Association can equip patients with tools they can implement under their clinician’s guidance. A provider’s greatest ally in diabetes care is a registered dietitian nutritionist (RDN) who is a Certified Diabetes Care and Education Specialist. RDNs will determine specific energy and nutrient needs and provide medical nutrition therapy such as carbohydrate counting, simplified meal plans, healthy food choices, exchange lists, and behavior strategies to help patients manage their diabetes. Many insurance plans cover these services.

What additional comments would you like to share with clinicians whose patients may ask them about the oatzempic diet?

Dr. Passerrello: What we do consistently matters. If your patient likes the taste of oatzempic in one meal a day, it’s a way to get more oats into their diet, if they focus their other meals on vegetables, fruits, whole grains, lean protein, and unsaturated fats.

Diets are out, and sustainable dietary patterns are in. Diets are one-size-fits-all, whereas a sustainable dietary pattern is individualized based on a person’s goals, medical history, taste preferences, budget, and lifestyle. Visit MyPlate.gov or work with an RDN [visit https://www.eatright.org/find-a-nutrition-expert to find nutritionists near your patients] to determine what a sustainable dietary pattern looks like.

What do clinicians need to know about claims on social media that a related drink — ‘ricezempic’ — aids weight loss?

Dr. Laing: Ricezempic promoters claim that drinking the beverage — typically made by soaking 1/2 cup of uncooked white rice in 1 cup of water and the juice from half a lime, then discarding the rice and drinking the liquid before breakfast — will lead to weight loss because the strained water provides a small dose of resistant starch, which is a source of prebiotics. Studies have shown that ingesting prebiotics may help lower blood cholesterol, improve blood glucose and insulin sensitivity, and benefit digestive function; however, more research is needed to determine specifics and if prebiotics are proven for weight loss.

Does ricezempic work?

Dr. Laing: There is no evidence that this concoction provides the same outcomes as GLP-1 agonists. The diet and the drug are not similar in mechanism of action or strength of scientific evidence to support their role in diabetes and weight management. Even if ricezempic provides a small amount of resistant starch and hydration from the rice water and citric acid from the lime juice, it is missing fiber, protein, healthy fats, and other vitamins and minerals that enhance the nutrient content of a meal or snack and stabilize blood sugar.

What advice do you have for clinicians whose patients with diabetes ask them about ricezempic?

Dr. Laing: I would not suggest that patients rely on ricezempic to support their health. There is no scientific evidence to show that people will lose weight in the short or long term by drinking ricezempic before a meal (or as a meal replacement).

If your patients are aiming to increase their intake of prebiotics, they are naturally found in various vegetables, fruits, whole grains, and seeds and in yogurt and high-fiber breads and cereals. A nutritious eating pattern that includes these foods is most beneficial for health.

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

A so-called “oatzempic” diet has been bouncing around the internet posing as a cheap — and available — weight loss alternative to Ozempic.

Fans of the diet, made trendy by TikTok postings and a clever name, claim that an oat-based smoothie helps people quickly shed lots of weight. The smoothie is made by blending 1/2 cup of oats, 1 cup of water, a squeeze of lime, and maybe a dash of cinnamon or other flavoring agents, typically as the first meal of the day, often after fasting, followed by normal meals.

Despite the hype, the oatzempic drink is a far cry from Ozempic (semaglutide), the glucagon-like peptide 1 (GLP-1) medication the Food and Drug Administration has approved only for type 2 diabetes management but used off label for weight loss.

So how do pulverized oats stack up against prescription-based GLP-1s? According to two nutrition experts, they’re not as effective as some TikTok influencers claim. And in people with diabetes, the diet can be dangerous.
 

Nutritionists Answer Questions on Oatzempic

Caroline West Passerrello, EdD, RDN, LDN, an instructor and community coordinator in the School of Health and Rehabilitation Sciences at the University of Pittsburgh, Pennsylvania, and Emma Laing, PhD, RDN, LD, a clinical professor and director of dietetics in the College of Family and Consumer Sciences at the University of Georgia, Athens, talked about this fad in emails.

Can the ‘oatzempic’ diet help people lose weight?

Dr. Passerrello: Oats are particularly high in soluble fiber, and high-fiber foods can increase the natural production of GLPs. But studies are mixed on whether this happens when eating oats.

The high content of soluble beta-glucan fiber in oats and the appetite-suppressing citric acid in lime can potentially promote decreased appetite and increased satiety. But a bowl of oatmeal, though not as trendy, will probably produce the same results.

Is the oatzempic diet safe for people with type 2 diabetes?

Dr. Laing: This diet has the potential to cause harm. The diet and the drug are not similar in mechanism of action or strength of scientific evidence to support their role in diabetes and weight management. There is no evidence that this concoction provides the same outcomes as GLP-1 agonists. Rapid weight loss is unsustainable and can be harmful, and frequent spikes in blood sugar can harm adults and children with diabetes. So the oatzempic diet’s safety depends on the rate of weight loss and the effect on blood sugar. While it provides beta-glucan from oats and citric acid from lime juice, it is missing protein, healthy fats, and other vitamins and minerals that enhance the nutrient content and stabilize blood sugar.

Maintaining relatively consistent, normal-range blood glucose concentrations is key for managing diabetes and lowering the risks for other health complications. Carbohydrate sources consumed on their own can produce greater blood sugar fluctuations than when combined with proteins and fats, which slow carbohydrate digestion speed. So pairing oats with fruits, vegetables, healthy fats, and protein sources enhances the flavor, texture, and nutrient composition of the dish and can help slow the postprandial rise in blood glucose.

In the long term, any restrictive fad diet likely cannot be sustained and increases the risk for malnutrition, metabolic rate slowing to conserve energy, depression, social isolation, or eating disorder.

Additional considerations apply to children, with or without diabetes. Restrictive, extreme diets that promise quick results typically “work” by promoting body water and muscle mass losses. Such diets are not only contraindicated in children, who are undergoing rapid growth and development, but also unsustainable and can lead to physical and psychological problems that carry into adulthood.

What strategies and tactics can physicians use to effectively communicate with their patients about safe and effective diets?

Dr. Laing: Encourage patients to be skeptical of social media trends that seem too good to be true. Many [social media] creators lack the education or professional credentials to offer sound nutrition advice, and their posts could do harm. Explain that individual nutrition needs differ considerably based on age, activity patterns, health conditions, and medications, and one person’s way of eating or success is often not realistic for someone else.

Encourage open dialogue and provide nonjudgmental advice. If the taste of oatzempic intrigues patients, there is likely no harm in experimenting. Work on ensuring their meals are adequate in calories and contain sources of protein and healthy fats to prevent spikes in blood glucose. It’s crucial to communicate that weight loss doesn’t always equate with improved health.

Sharing information from the Academy of Nutrition and Dietetics and the American Diabetes Association can equip patients with tools they can implement under their clinician’s guidance. A provider’s greatest ally in diabetes care is a registered dietitian nutritionist (RDN) who is a Certified Diabetes Care and Education Specialist. RDNs will determine specific energy and nutrient needs and provide medical nutrition therapy such as carbohydrate counting, simplified meal plans, healthy food choices, exchange lists, and behavior strategies to help patients manage their diabetes. Many insurance plans cover these services.

What additional comments would you like to share with clinicians whose patients may ask them about the oatzempic diet?

Dr. Passerrello: What we do consistently matters. If your patient likes the taste of oatzempic in one meal a day, it’s a way to get more oats into their diet, if they focus their other meals on vegetables, fruits, whole grains, lean protein, and unsaturated fats.

Diets are out, and sustainable dietary patterns are in. Diets are one-size-fits-all, whereas a sustainable dietary pattern is individualized based on a person’s goals, medical history, taste preferences, budget, and lifestyle. Visit MyPlate.gov or work with an RDN [visit https://www.eatright.org/find-a-nutrition-expert to find nutritionists near your patients] to determine what a sustainable dietary pattern looks like.

What do clinicians need to know about claims on social media that a related drink — ‘ricezempic’ — aids weight loss?

Dr. Laing: Ricezempic promoters claim that drinking the beverage — typically made by soaking 1/2 cup of uncooked white rice in 1 cup of water and the juice from half a lime, then discarding the rice and drinking the liquid before breakfast — will lead to weight loss because the strained water provides a small dose of resistant starch, which is a source of prebiotics. Studies have shown that ingesting prebiotics may help lower blood cholesterol, improve blood glucose and insulin sensitivity, and benefit digestive function; however, more research is needed to determine specifics and if prebiotics are proven for weight loss.

Does ricezempic work?

Dr. Laing: There is no evidence that this concoction provides the same outcomes as GLP-1 agonists. The diet and the drug are not similar in mechanism of action or strength of scientific evidence to support their role in diabetes and weight management. Even if ricezempic provides a small amount of resistant starch and hydration from the rice water and citric acid from the lime juice, it is missing fiber, protein, healthy fats, and other vitamins and minerals that enhance the nutrient content of a meal or snack and stabilize blood sugar.

What advice do you have for clinicians whose patients with diabetes ask them about ricezempic?

Dr. Laing: I would not suggest that patients rely on ricezempic to support their health. There is no scientific evidence to show that people will lose weight in the short or long term by drinking ricezempic before a meal (or as a meal replacement).

If your patients are aiming to increase their intake of prebiotics, they are naturally found in various vegetables, fruits, whole grains, and seeds and in yogurt and high-fiber breads and cereals. A nutritious eating pattern that includes these foods is most beneficial for health.

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

LONDON — Potassium supplementation does not alter the risk for postoperative atrial fibrillation in patients who have undergone cardiac surgery, contrary to expectations and popular clinical practice, new trial results demonstrate.

“The widespread practice of giving patients potassium after bypass heart surgery even though their blood levels are within the normal range can be abandoned,” said Benjamin O’Brien, MD, PhD, director of the Clinic for Cardioanesthesiology and Intensive Care Medicine at Charité Hospital in Berlin, Germany.

Results from the randomized TIGHT-K trial that assessed two levels of potassium supplementation were presented at the annual congress of the European Society of Cardiology.

In the tight-control group, supplementation was provided to maintain high-normal levels of potassium (> 4.5 mEq/L). In the relaxed-control group, supplementation was provided only when potassium levels fell below the low-normal threshold (< 3.6 mEq/L). 
 

Trial Upending Popular Practice

The multinational trial involved 23 centers in Germany and the United Kingdom. All 1690 participants enrolled were scheduled to undergo a coronary artery bypass graft procedure, but Dr. O’Brien said he considers the results of TIGHT-K to be broadly applicable.

“There is no physiological basis to expect a different result in patients undergoing different types of cardiac surgery,” he said.

The primary endpoint was clinically and electrocardiography confirmed new-onset atrial fibrillation that occurred in the 5 days after the bypass procedure.

For the primary atrial fibrillation endpoint, event rates were similar in the tight-control and the relaxed-control groups (26.2% vs 27.8%); the 1.7% difference did not approach statistical significance (P = .44). The difference in dysrhythmias other than atrial fibrillation, although numerically lower in the tight-control group, was also not significant (19.1% vs 21.1%; P = .26).

There were no significant differences in several secondary endpoints, including length of hospital stay and in-patient mortality, but cost, a prespecified secondary endpoint, was approximately $120 lower per patient in the relaxed-control group than in the tight-control group (P < .001).
 

Lowering Cost Across Cardiac Surgeries

During the 5-day follow-up, median potassium levels were higher in the tight-control group. Levels in both groups fell gradually, but essentially in parallel, over the study period, so median potassium levels were always higher in the tight-control group than in the relaxed-control group. At the end of the observation period, mean potassium levels were 4.34 mEq/L in the tight-control group and 4.08 mEq/L in the relaxed-control group.

Prior to the development of atrial fibrillation, participants in the tight-control group received a medium of seven potassium administrations (range, 4-12), whereas those in the relaxed-control group received a medium of zero.

There were no significant differences in episodes in any subgroup evaluated, including those divided by age, sex, baseline left ventricular ejection fraction, and the absence or presence of beta blockers or loop diuretics. A per-protocol analysis also failed to show any advantage for tight potassium control.

Atrial fibrillation occurs in about one third of patients after bypass surgery, as it does after many types of cardiac surgery. Institutions often have strategies in place to reduce the risk after cardiac surgery, and potassium supplementation is one of the most common, despite the lack of supportive evidence, Dr. O’Brien said.
 

Narrow Window for Optimal Potassium Levels

The difference in potassium levels between the tight-control group and the relaxed-control group were modest in this study, said Subodh Verma, MD, a cardiac surgeon at St Michael’s Hospital and professor at the University of Toronto, Ontario, Canada.

However, this is unavoidable and central to the question being posed, Dr. O’Brien pointed out. Because of the risks for both hypokalemia and hyperkalemia, the window for safe supplementation is short. Current practice is to achieve high-normal levels to reduce atrial fibrillation, but TIGHT-K demonstrates this has no benefit.

The conclusion of TIGHT-K is appropriate, said Faiez Zannad, MD, PhD, professor of therapeutics in the Division of Cardiology at the University of Lorraine in Nancy, France, who praised the design and conduct of the study.

He acknowledged an unmet need for effective methods to reduce the risk for atrial fibrillation after cardiac surgery, but the ESC invited discussant said it is now necessary to look at other strategies. Several are under current evaluation, such as supplementary magnesium and the use of sodium-glucose transporter-2 inhibitors.

Although Dr. Zannad encouraged more studies of methods to reduce atrial fibrillation risk after cardiac surgery, he said that TIGHT-K has answered the question of whether potassium supplementation is beneficial.

Potassium supplementation should no longer be offered, he said, which will “reduce healthcare costs and decrease patient risk from an unnecessary intervention.”

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

LONDON — Potassium supplementation does not alter the risk for postoperative atrial fibrillation in patients who have undergone cardiac surgery, contrary to expectations and popular clinical practice, new trial results demonstrate.

“The widespread practice of giving patients potassium after bypass heart surgery even though their blood levels are within the normal range can be abandoned,” said Benjamin O’Brien, MD, PhD, director of the Clinic for Cardioanesthesiology and Intensive Care Medicine at Charité Hospital in Berlin, Germany.

Results from the randomized TIGHT-K trial that assessed two levels of potassium supplementation were presented at the annual congress of the European Society of Cardiology.

In the tight-control group, supplementation was provided to maintain high-normal levels of potassium (> 4.5 mEq/L). In the relaxed-control group, supplementation was provided only when potassium levels fell below the low-normal threshold (< 3.6 mEq/L). 
 

Trial Upending Popular Practice

The multinational trial involved 23 centers in Germany and the United Kingdom. All 1690 participants enrolled were scheduled to undergo a coronary artery bypass graft procedure, but Dr. O’Brien said he considers the results of TIGHT-K to be broadly applicable.

“There is no physiological basis to expect a different result in patients undergoing different types of cardiac surgery,” he said.

The primary endpoint was clinically and electrocardiography confirmed new-onset atrial fibrillation that occurred in the 5 days after the bypass procedure.

For the primary atrial fibrillation endpoint, event rates were similar in the tight-control and the relaxed-control groups (26.2% vs 27.8%); the 1.7% difference did not approach statistical significance (P = .44). The difference in dysrhythmias other than atrial fibrillation, although numerically lower in the tight-control group, was also not significant (19.1% vs 21.1%; P = .26).

There were no significant differences in several secondary endpoints, including length of hospital stay and in-patient mortality, but cost, a prespecified secondary endpoint, was approximately $120 lower per patient in the relaxed-control group than in the tight-control group (P < .001).
 

Lowering Cost Across Cardiac Surgeries

During the 5-day follow-up, median potassium levels were higher in the tight-control group. Levels in both groups fell gradually, but essentially in parallel, over the study period, so median potassium levels were always higher in the tight-control group than in the relaxed-control group. At the end of the observation period, mean potassium levels were 4.34 mEq/L in the tight-control group and 4.08 mEq/L in the relaxed-control group.

Prior to the development of atrial fibrillation, participants in the tight-control group received a medium of seven potassium administrations (range, 4-12), whereas those in the relaxed-control group received a medium of zero.

There were no significant differences in episodes in any subgroup evaluated, including those divided by age, sex, baseline left ventricular ejection fraction, and the absence or presence of beta blockers or loop diuretics. A per-protocol analysis also failed to show any advantage for tight potassium control.

Atrial fibrillation occurs in about one third of patients after bypass surgery, as it does after many types of cardiac surgery. Institutions often have strategies in place to reduce the risk after cardiac surgery, and potassium supplementation is one of the most common, despite the lack of supportive evidence, Dr. O’Brien said.
 

Narrow Window for Optimal Potassium Levels

The difference in potassium levels between the tight-control group and the relaxed-control group were modest in this study, said Subodh Verma, MD, a cardiac surgeon at St Michael’s Hospital and professor at the University of Toronto, Ontario, Canada.

However, this is unavoidable and central to the question being posed, Dr. O’Brien pointed out. Because of the risks for both hypokalemia and hyperkalemia, the window for safe supplementation is short. Current practice is to achieve high-normal levels to reduce atrial fibrillation, but TIGHT-K demonstrates this has no benefit.

The conclusion of TIGHT-K is appropriate, said Faiez Zannad, MD, PhD, professor of therapeutics in the Division of Cardiology at the University of Lorraine in Nancy, France, who praised the design and conduct of the study.

He acknowledged an unmet need for effective methods to reduce the risk for atrial fibrillation after cardiac surgery, but the ESC invited discussant said it is now necessary to look at other strategies. Several are under current evaluation, such as supplementary magnesium and the use of sodium-glucose transporter-2 inhibitors.

Although Dr. Zannad encouraged more studies of methods to reduce atrial fibrillation risk after cardiac surgery, he said that TIGHT-K has answered the question of whether potassium supplementation is beneficial.

Potassium supplementation should no longer be offered, he said, which will “reduce healthcare costs and decrease patient risk from an unnecessary intervention.”

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

LONDON — Potassium supplementation does not alter the risk for postoperative atrial fibrillation in patients who have undergone cardiac surgery, contrary to expectations and popular clinical practice, new trial results demonstrate.

“The widespread practice of giving patients potassium after bypass heart surgery even though their blood levels are within the normal range can be abandoned,” said Benjamin O’Brien, MD, PhD, director of the Clinic for Cardioanesthesiology and Intensive Care Medicine at Charité Hospital in Berlin, Germany.

Results from the randomized TIGHT-K trial that assessed two levels of potassium supplementation were presented at the annual congress of the European Society of Cardiology.

In the tight-control group, supplementation was provided to maintain high-normal levels of potassium (> 4.5 mEq/L). In the relaxed-control group, supplementation was provided only when potassium levels fell below the low-normal threshold (< 3.6 mEq/L). 
 

Trial Upending Popular Practice

The multinational trial involved 23 centers in Germany and the United Kingdom. All 1690 participants enrolled were scheduled to undergo a coronary artery bypass graft procedure, but Dr. O’Brien said he considers the results of TIGHT-K to be broadly applicable.

“There is no physiological basis to expect a different result in patients undergoing different types of cardiac surgery,” he said.

The primary endpoint was clinically and electrocardiography confirmed new-onset atrial fibrillation that occurred in the 5 days after the bypass procedure.

For the primary atrial fibrillation endpoint, event rates were similar in the tight-control and the relaxed-control groups (26.2% vs 27.8%); the 1.7% difference did not approach statistical significance (P = .44). The difference in dysrhythmias other than atrial fibrillation, although numerically lower in the tight-control group, was also not significant (19.1% vs 21.1%; P = .26).

There were no significant differences in several secondary endpoints, including length of hospital stay and in-patient mortality, but cost, a prespecified secondary endpoint, was approximately $120 lower per patient in the relaxed-control group than in the tight-control group (P < .001).
 

Lowering Cost Across Cardiac Surgeries

During the 5-day follow-up, median potassium levels were higher in the tight-control group. Levels in both groups fell gradually, but essentially in parallel, over the study period, so median potassium levels were always higher in the tight-control group than in the relaxed-control group. At the end of the observation period, mean potassium levels were 4.34 mEq/L in the tight-control group and 4.08 mEq/L in the relaxed-control group.

Prior to the development of atrial fibrillation, participants in the tight-control group received a medium of seven potassium administrations (range, 4-12), whereas those in the relaxed-control group received a medium of zero.

There were no significant differences in episodes in any subgroup evaluated, including those divided by age, sex, baseline left ventricular ejection fraction, and the absence or presence of beta blockers or loop diuretics. A per-protocol analysis also failed to show any advantage for tight potassium control.

Atrial fibrillation occurs in about one third of patients after bypass surgery, as it does after many types of cardiac surgery. Institutions often have strategies in place to reduce the risk after cardiac surgery, and potassium supplementation is one of the most common, despite the lack of supportive evidence, Dr. O’Brien said.
 

Narrow Window for Optimal Potassium Levels

The difference in potassium levels between the tight-control group and the relaxed-control group were modest in this study, said Subodh Verma, MD, a cardiac surgeon at St Michael’s Hospital and professor at the University of Toronto, Ontario, Canada.

However, this is unavoidable and central to the question being posed, Dr. O’Brien pointed out. Because of the risks for both hypokalemia and hyperkalemia, the window for safe supplementation is short. Current practice is to achieve high-normal levels to reduce atrial fibrillation, but TIGHT-K demonstrates this has no benefit.

The conclusion of TIGHT-K is appropriate, said Faiez Zannad, MD, PhD, professor of therapeutics in the Division of Cardiology at the University of Lorraine in Nancy, France, who praised the design and conduct of the study.

He acknowledged an unmet need for effective methods to reduce the risk for atrial fibrillation after cardiac surgery, but the ESC invited discussant said it is now necessary to look at other strategies. Several are under current evaluation, such as supplementary magnesium and the use of sodium-glucose transporter-2 inhibitors.

Although Dr. Zannad encouraged more studies of methods to reduce atrial fibrillation risk after cardiac surgery, he said that TIGHT-K has answered the question of whether potassium supplementation is beneficial.

Potassium supplementation should no longer be offered, he said, which will “reduce healthcare costs and decrease patient risk from an unnecessary intervention.”

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

This transcript has been edited for clarity.

Tricia Ward: I’m joined today by Dr. Scott R. Garrison, MD, PhD. He is a professor in the Department of Family Medicine at the University of Alberta in Edmonton, Alberta, Canada, and director of the Pragmatic Trials Collaborative.

You presented two studies at ESC. One is the BedMed study, comparing day vs nighttime dosing of blood pressure therapy. Can you tell us the top-line findings? 
 

BedMed and BedMed-Frail

Dr. Garrison: We were looking to validate an earlier study that suggested a large benefit of taking blood pressure medication at bedtime, as far as reducing major adverse cardiovascular events (MACEs). That was the MAPEC study. They suggested a 60% reduction. The BedMed trial was in hypertensive primary care patients in five Canadian provinces. We randomized well over 3000 patients to bedtime or morning medications. We looked at MACEs — so all-cause death or hospitalizations for acute coronary syndrome, stroke, or heart failure, and a bunch of safety outcomes.

Essentially, we found that it made absolutely no difference whatever time of day you took it in terms of MACEs and it didn’t make any difference to the adverse effects. It was safe to take it at bedtime. But it did not convey any extra cardiovascular benefit.

Ms. Ward: And then you did a second study, called BedMed-Frail. Do you want to tell us the reason you did that?

Dr. Garrison: BedMed-Frail took place in a nursing home population. We believed that it was possible that frail, older adults might have very different risks and benefits, and that they would probably be underrepresented, as they normally are in the main trial. 

We thought that because bedtime blood pressure medications would be theoretically preferentially lowering night pressure, which is already the lowest pressure of the day, that if you were at risk for hypotensive or ischemic adverse events, that might make it worse. We looked at falls and fractures; worsening cognition in case they had vascular dementia; and whether they developed decubitus ulcers (pressure sores) because you need a certain amount of pressure to get past any obstruction — in this case, it’s the weight of your body if you’re lying in bed all the time. 

We also looked at problem behaviors. People who have dementia have what’s called “sundowning,” where agitation and confusion are worse as the evening is going on. We looked at that on the off chance that it had anything to do with blood pressures being lower. And the BedMed-Frail results mirror those of BedMed exactly. So there was no cardiovascular benefit, and in this population, that was largely driven by mortality; one third of these people died every year. 

Ms. Ward: The median age was about 88?

Dr. Garrison: Yes, the median age was 88. There was no cardiovascular mortality advantage to bedtime dosing, but neither was there any signal of safety concerns. 
 

Other Complementary and Conflicting Studies

Ms. Ward: These two studies mirror the TIME study from the United Kingdom.

Dr. Garrison: Yes. We found exactly what TIME found. Our point estimate was pretty much the same. The hazard ratio in the main trial was 0.96. Theirs, I believe, was 0.95. Our findings agree completely with those of TIME and differ substantially from the previous trials that suggested a large benefit.

Ms. Ward: Those previous trials were MAPEC and the Hygia Chronotherapy Trial.

Dr. Garrison: MAPEC was the first one. While we were doing our trial, and while the TIME investigators were doing their trial, both of us trying to validate MAPEC, the same group published another study called Hygia, which also reported a large reduction: a 45% reduction in MACE with bedtime dosing.

Ms. Ward: You didn’t present it, but there was also a meta-analysis presented here by somebody independent.

Dr. Garrison: Yes, Ricky Turgeon. I know Ricky. We gave him patient-level data for his meta-analysis, but I was not otherwise involved. 

Ms. Ward: And the conclusion is the same.

Dr. Garrison: It’s the same. He only found the same five trials: MAPEC, Hygia, TIME, BedMed, and BedMed-Frail. Combining them all together, the CIs still span 1.0, so it didn’t end up being significant. But he also analyzed TIME and the BedMed trials separately — again suggesting that those trials showed no benefit.

Ms. Ward: There was a TIME substudy of night owls vs early risers or morning people, and there was a hint (or whatever you should say for a subanalysis of a neutral trial) that timing might make a difference there.

Dr. Garrison: They recently published, I guess it is a substudy, where they looked at people’s chronotype according to whether you consider yourself an early bird or a night owl. Their assessment was more detailed. They reported that if people were tending toward being early birds and they took their blood pressure medicine in the morning, or if they were night owls and they took it in the evening, that they tended to have statistically significantly better outcomes than the opposite timing. In that analysis, they were only looking at nonfatal myocardial infarction and nonfatal stroke. 

We did ask something that was related. We asked people: “Do we consider yourself more of an early bird or a night owl?” So we do have those data. For what I presented at ESC, we just looked at the primary outcome; we did subgroups according to early bird, night owl, and neither, and that was not statistically significant. It didn’t rule it out. There were some trends in the direction that the TIME group were suggesting. We do intend to do a closer look at that. 

But, you know, they call these “late-breaking trials,” and it really was in our case. We didn’t get the last of our data from the last province until the end of June, so we still are finishing up the analysis of the chronotype portion — so more to come in another month or so.
 

Do What You Like, or Stick to Morning Dosing?

Ms. Ward: For the purposes of people’s take-home message, does this mostly apply to once-daily–dosed antihypertensives?

Dr. Garrison: It was essentially once-daily medicines that were changed. The docs did have the opportunity to consolidate twice-daily meds into once-daily or switch to a different medication. That’s probably the area where adherence was the biggest issue, because it’s largely beta-blockers that were given twice daily at baseline, and they were less likely to want to change. 

At 6 months, 83% of once-daily medications were taken per allocation in the bedtime group and 95% per allocation in the morning group, which was actually pretty good. For angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and calcium-channel blockers, the adherence was excellent. Again, it was beta-blockers taken twice a day where it fell down, and then also diuretics. But if you combine all diuretic medications (ie, pure diuretics and combo agents), still, 75% of them were successful at taking them at bedtime. Only 15% of people switching a diuretic to bedtime dosing actually had problems with nocturia. Most physicians think that they can’t get their patients to take those meds at bedtime, but you can. There’s probably no reason to take it at bedtime, but most people do tolerate it.

Ms. Ward: Is your advice to take it whenever you feel like? I know when TIME came out, Professor George Stergiou, who’s the incoming president of the International Society of Hypertension, said, well, maybe we should stick with the morning, because that’s what most of the trials did. 

Dr. Garrison: I think that›s a perfectly valid point of view, and maybe for a lot of people, that could be the default. There are some people, though, who will have a particular reason why one time is better. For instance, most people have no problems with calcium-channel blockers, but some get ankle swelling and you’re more likely to have that happen if you take them in the morning. Or lots of people want to take all their pills at the same time; blood pressure pills are easy ones to switch the timing of if you’re trying to accomplish that, and if that will help adherence. Basically, whatever time of day you can remember to take it the best is probably the right time.

Ms. Ward: Given where we are today, with your trials and TIME, do you think this is now settled science that it doesn’t make a difference?

Dr. Garrison: I’m probably the wrong person to ask, because I clearly have a bias. I think the methods in the TIME trial are really transparent and solid. I hope that when our papers come out, people will feel the same. You just have to look at the different trials. You need people like Dr. Stergiou to wade through the trials to help you with that.

Ms. Ward: Thank you very much for joining me today and discussing this trial.

Scott R. Garrison, MD, PhD, is Professor, Department of Family Medicine, University of Alberta in Edmonton, Alberta, Canada, and Staff Physician, Department of Family Medicine, Kaye Edmonton Clinic, and he has disclosed receiving research grants from Alberta Innovates (the Alberta Provincial Government) and the Canadian Institutes of Health Research (the Canadian Federal Government).

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

This transcript has been edited for clarity.

Tricia Ward: I’m joined today by Dr. Scott R. Garrison, MD, PhD. He is a professor in the Department of Family Medicine at the University of Alberta in Edmonton, Alberta, Canada, and director of the Pragmatic Trials Collaborative.

You presented two studies at ESC. One is the BedMed study, comparing day vs nighttime dosing of blood pressure therapy. Can you tell us the top-line findings? 
 

BedMed and BedMed-Frail

Dr. Garrison: We were looking to validate an earlier study that suggested a large benefit of taking blood pressure medication at bedtime, as far as reducing major adverse cardiovascular events (MACEs). That was the MAPEC study. They suggested a 60% reduction. The BedMed trial was in hypertensive primary care patients in five Canadian provinces. We randomized well over 3000 patients to bedtime or morning medications. We looked at MACEs — so all-cause death or hospitalizations for acute coronary syndrome, stroke, or heart failure, and a bunch of safety outcomes.

Essentially, we found that it made absolutely no difference whatever time of day you took it in terms of MACEs and it didn’t make any difference to the adverse effects. It was safe to take it at bedtime. But it did not convey any extra cardiovascular benefit.

Ms. Ward: And then you did a second study, called BedMed-Frail. Do you want to tell us the reason you did that?

Dr. Garrison: BedMed-Frail took place in a nursing home population. We believed that it was possible that frail, older adults might have very different risks and benefits, and that they would probably be underrepresented, as they normally are in the main trial. 

We thought that because bedtime blood pressure medications would be theoretically preferentially lowering night pressure, which is already the lowest pressure of the day, that if you were at risk for hypotensive or ischemic adverse events, that might make it worse. We looked at falls and fractures; worsening cognition in case they had vascular dementia; and whether they developed decubitus ulcers (pressure sores) because you need a certain amount of pressure to get past any obstruction — in this case, it’s the weight of your body if you’re lying in bed all the time. 

We also looked at problem behaviors. People who have dementia have what’s called “sundowning,” where agitation and confusion are worse as the evening is going on. We looked at that on the off chance that it had anything to do with blood pressures being lower. And the BedMed-Frail results mirror those of BedMed exactly. So there was no cardiovascular benefit, and in this population, that was largely driven by mortality; one third of these people died every year. 

Ms. Ward: The median age was about 88?

Dr. Garrison: Yes, the median age was 88. There was no cardiovascular mortality advantage to bedtime dosing, but neither was there any signal of safety concerns. 
 

Other Complementary and Conflicting Studies

Ms. Ward: These two studies mirror the TIME study from the United Kingdom.

Dr. Garrison: Yes. We found exactly what TIME found. Our point estimate was pretty much the same. The hazard ratio in the main trial was 0.96. Theirs, I believe, was 0.95. Our findings agree completely with those of TIME and differ substantially from the previous trials that suggested a large benefit.

Ms. Ward: Those previous trials were MAPEC and the Hygia Chronotherapy Trial.

Dr. Garrison: MAPEC was the first one. While we were doing our trial, and while the TIME investigators were doing their trial, both of us trying to validate MAPEC, the same group published another study called Hygia, which also reported a large reduction: a 45% reduction in MACE with bedtime dosing.

Ms. Ward: You didn’t present it, but there was also a meta-analysis presented here by somebody independent.

Dr. Garrison: Yes, Ricky Turgeon. I know Ricky. We gave him patient-level data for his meta-analysis, but I was not otherwise involved. 

Ms. Ward: And the conclusion is the same.

Dr. Garrison: It’s the same. He only found the same five trials: MAPEC, Hygia, TIME, BedMed, and BedMed-Frail. Combining them all together, the CIs still span 1.0, so it didn’t end up being significant. But he also analyzed TIME and the BedMed trials separately — again suggesting that those trials showed no benefit.

Ms. Ward: There was a TIME substudy of night owls vs early risers or morning people, and there was a hint (or whatever you should say for a subanalysis of a neutral trial) that timing might make a difference there.

Dr. Garrison: They recently published, I guess it is a substudy, where they looked at people’s chronotype according to whether you consider yourself an early bird or a night owl. Their assessment was more detailed. They reported that if people were tending toward being early birds and they took their blood pressure medicine in the morning, or if they were night owls and they took it in the evening, that they tended to have statistically significantly better outcomes than the opposite timing. In that analysis, they were only looking at nonfatal myocardial infarction and nonfatal stroke. 

We did ask something that was related. We asked people: “Do we consider yourself more of an early bird or a night owl?” So we do have those data. For what I presented at ESC, we just looked at the primary outcome; we did subgroups according to early bird, night owl, and neither, and that was not statistically significant. It didn’t rule it out. There were some trends in the direction that the TIME group were suggesting. We do intend to do a closer look at that. 

But, you know, they call these “late-breaking trials,” and it really was in our case. We didn’t get the last of our data from the last province until the end of June, so we still are finishing up the analysis of the chronotype portion — so more to come in another month or so.
 

Do What You Like, or Stick to Morning Dosing?

Ms. Ward: For the purposes of people’s take-home message, does this mostly apply to once-daily–dosed antihypertensives?

Dr. Garrison: It was essentially once-daily medicines that were changed. The docs did have the opportunity to consolidate twice-daily meds into once-daily or switch to a different medication. That’s probably the area where adherence was the biggest issue, because it’s largely beta-blockers that were given twice daily at baseline, and they were less likely to want to change. 

At 6 months, 83% of once-daily medications were taken per allocation in the bedtime group and 95% per allocation in the morning group, which was actually pretty good. For angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and calcium-channel blockers, the adherence was excellent. Again, it was beta-blockers taken twice a day where it fell down, and then also diuretics. But if you combine all diuretic medications (ie, pure diuretics and combo agents), still, 75% of them were successful at taking them at bedtime. Only 15% of people switching a diuretic to bedtime dosing actually had problems with nocturia. Most physicians think that they can’t get their patients to take those meds at bedtime, but you can. There’s probably no reason to take it at bedtime, but most people do tolerate it.

Ms. Ward: Is your advice to take it whenever you feel like? I know when TIME came out, Professor George Stergiou, who’s the incoming president of the International Society of Hypertension, said, well, maybe we should stick with the morning, because that’s what most of the trials did. 

Dr. Garrison: I think that›s a perfectly valid point of view, and maybe for a lot of people, that could be the default. There are some people, though, who will have a particular reason why one time is better. For instance, most people have no problems with calcium-channel blockers, but some get ankle swelling and you’re more likely to have that happen if you take them in the morning. Or lots of people want to take all their pills at the same time; blood pressure pills are easy ones to switch the timing of if you’re trying to accomplish that, and if that will help adherence. Basically, whatever time of day you can remember to take it the best is probably the right time.

Ms. Ward: Given where we are today, with your trials and TIME, do you think this is now settled science that it doesn’t make a difference?

Dr. Garrison: I’m probably the wrong person to ask, because I clearly have a bias. I think the methods in the TIME trial are really transparent and solid. I hope that when our papers come out, people will feel the same. You just have to look at the different trials. You need people like Dr. Stergiou to wade through the trials to help you with that.

Ms. Ward: Thank you very much for joining me today and discussing this trial.

Scott R. Garrison, MD, PhD, is Professor, Department of Family Medicine, University of Alberta in Edmonton, Alberta, Canada, and Staff Physician, Department of Family Medicine, Kaye Edmonton Clinic, and he has disclosed receiving research grants from Alberta Innovates (the Alberta Provincial Government) and the Canadian Institutes of Health Research (the Canadian Federal Government).

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

This transcript has been edited for clarity.

Tricia Ward: I’m joined today by Dr. Scott R. Garrison, MD, PhD. He is a professor in the Department of Family Medicine at the University of Alberta in Edmonton, Alberta, Canada, and director of the Pragmatic Trials Collaborative.

You presented two studies at ESC. One is the BedMed study, comparing day vs nighttime dosing of blood pressure therapy. Can you tell us the top-line findings? 
 

BedMed and BedMed-Frail

Dr. Garrison: We were looking to validate an earlier study that suggested a large benefit of taking blood pressure medication at bedtime, as far as reducing major adverse cardiovascular events (MACEs). That was the MAPEC study. They suggested a 60% reduction. The BedMed trial was in hypertensive primary care patients in five Canadian provinces. We randomized well over 3000 patients to bedtime or morning medications. We looked at MACEs — so all-cause death or hospitalizations for acute coronary syndrome, stroke, or heart failure, and a bunch of safety outcomes.

Essentially, we found that it made absolutely no difference whatever time of day you took it in terms of MACEs and it didn’t make any difference to the adverse effects. It was safe to take it at bedtime. But it did not convey any extra cardiovascular benefit.

Ms. Ward: And then you did a second study, called BedMed-Frail. Do you want to tell us the reason you did that?

Dr. Garrison: BedMed-Frail took place in a nursing home population. We believed that it was possible that frail, older adults might have very different risks and benefits, and that they would probably be underrepresented, as they normally are in the main trial. 

We thought that because bedtime blood pressure medications would be theoretically preferentially lowering night pressure, which is already the lowest pressure of the day, that if you were at risk for hypotensive or ischemic adverse events, that might make it worse. We looked at falls and fractures; worsening cognition in case they had vascular dementia; and whether they developed decubitus ulcers (pressure sores) because you need a certain amount of pressure to get past any obstruction — in this case, it’s the weight of your body if you’re lying in bed all the time. 

We also looked at problem behaviors. People who have dementia have what’s called “sundowning,” where agitation and confusion are worse as the evening is going on. We looked at that on the off chance that it had anything to do with blood pressures being lower. And the BedMed-Frail results mirror those of BedMed exactly. So there was no cardiovascular benefit, and in this population, that was largely driven by mortality; one third of these people died every year. 

Ms. Ward: The median age was about 88?

Dr. Garrison: Yes, the median age was 88. There was no cardiovascular mortality advantage to bedtime dosing, but neither was there any signal of safety concerns. 
 

Other Complementary and Conflicting Studies

Ms. Ward: These two studies mirror the TIME study from the United Kingdom.

Dr. Garrison: Yes. We found exactly what TIME found. Our point estimate was pretty much the same. The hazard ratio in the main trial was 0.96. Theirs, I believe, was 0.95. Our findings agree completely with those of TIME and differ substantially from the previous trials that suggested a large benefit.

Ms. Ward: Those previous trials were MAPEC and the Hygia Chronotherapy Trial.

Dr. Garrison: MAPEC was the first one. While we were doing our trial, and while the TIME investigators were doing their trial, both of us trying to validate MAPEC, the same group published another study called Hygia, which also reported a large reduction: a 45% reduction in MACE with bedtime dosing.

Ms. Ward: You didn’t present it, but there was also a meta-analysis presented here by somebody independent.

Dr. Garrison: Yes, Ricky Turgeon. I know Ricky. We gave him patient-level data for his meta-analysis, but I was not otherwise involved. 

Ms. Ward: And the conclusion is the same.

Dr. Garrison: It’s the same. He only found the same five trials: MAPEC, Hygia, TIME, BedMed, and BedMed-Frail. Combining them all together, the CIs still span 1.0, so it didn’t end up being significant. But he also analyzed TIME and the BedMed trials separately — again suggesting that those trials showed no benefit.

Ms. Ward: There was a TIME substudy of night owls vs early risers or morning people, and there was a hint (or whatever you should say for a subanalysis of a neutral trial) that timing might make a difference there.

Dr. Garrison: They recently published, I guess it is a substudy, where they looked at people’s chronotype according to whether you consider yourself an early bird or a night owl. Their assessment was more detailed. They reported that if people were tending toward being early birds and they took their blood pressure medicine in the morning, or if they were night owls and they took it in the evening, that they tended to have statistically significantly better outcomes than the opposite timing. In that analysis, they were only looking at nonfatal myocardial infarction and nonfatal stroke. 

We did ask something that was related. We asked people: “Do we consider yourself more of an early bird or a night owl?” So we do have those data. For what I presented at ESC, we just looked at the primary outcome; we did subgroups according to early bird, night owl, and neither, and that was not statistically significant. It didn’t rule it out. There were some trends in the direction that the TIME group were suggesting. We do intend to do a closer look at that. 

But, you know, they call these “late-breaking trials,” and it really was in our case. We didn’t get the last of our data from the last province until the end of June, so we still are finishing up the analysis of the chronotype portion — so more to come in another month or so.
 

Do What You Like, or Stick to Morning Dosing?

Ms. Ward: For the purposes of people’s take-home message, does this mostly apply to once-daily–dosed antihypertensives?

Dr. Garrison: It was essentially once-daily medicines that were changed. The docs did have the opportunity to consolidate twice-daily meds into once-daily or switch to a different medication. That’s probably the area where adherence was the biggest issue, because it’s largely beta-blockers that were given twice daily at baseline, and they were less likely to want to change. 

At 6 months, 83% of once-daily medications were taken per allocation in the bedtime group and 95% per allocation in the morning group, which was actually pretty good. For angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and calcium-channel blockers, the adherence was excellent. Again, it was beta-blockers taken twice a day where it fell down, and then also diuretics. But if you combine all diuretic medications (ie, pure diuretics and combo agents), still, 75% of them were successful at taking them at bedtime. Only 15% of people switching a diuretic to bedtime dosing actually had problems with nocturia. Most physicians think that they can’t get their patients to take those meds at bedtime, but you can. There’s probably no reason to take it at bedtime, but most people do tolerate it.

Ms. Ward: Is your advice to take it whenever you feel like? I know when TIME came out, Professor George Stergiou, who’s the incoming president of the International Society of Hypertension, said, well, maybe we should stick with the morning, because that’s what most of the trials did. 

Dr. Garrison: I think that›s a perfectly valid point of view, and maybe for a lot of people, that could be the default. There are some people, though, who will have a particular reason why one time is better. For instance, most people have no problems with calcium-channel blockers, but some get ankle swelling and you’re more likely to have that happen if you take them in the morning. Or lots of people want to take all their pills at the same time; blood pressure pills are easy ones to switch the timing of if you’re trying to accomplish that, and if that will help adherence. Basically, whatever time of day you can remember to take it the best is probably the right time.

Ms. Ward: Given where we are today, with your trials and TIME, do you think this is now settled science that it doesn’t make a difference?

Dr. Garrison: I’m probably the wrong person to ask, because I clearly have a bias. I think the methods in the TIME trial are really transparent and solid. I hope that when our papers come out, people will feel the same. You just have to look at the different trials. You need people like Dr. Stergiou to wade through the trials to help you with that.

Ms. Ward: Thank you very much for joining me today and discussing this trial.

Scott R. Garrison, MD, PhD, is Professor, Department of Family Medicine, University of Alberta in Edmonton, Alberta, Canada, and Staff Physician, Department of Family Medicine, Kaye Edmonton Clinic, and he has disclosed receiving research grants from Alberta Innovates (the Alberta Provincial Government) and the Canadian Institutes of Health Research (the Canadian Federal Government).

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

TOPLINE: 

Patients with both rheumatoid arthritis (RA) and atrial fibrillation (AF) have a higher risk for ischemic stroke than those with only AF. They are also less likely to receive oral anticoagulant treatment, which may contribute to this increased stroke risk.

METHODOLOGY:

• Researchers conducted a registry-based retrospective cohort study using the Norwegian Cardio-Rheuma Register to evaluate the risk for ischemic stroke following the diagnosis of AF in patients with or without RA.
• They included 163,595 patients with newly diagnosed AF between 2010 and 2017, of whom 2750 had RA. Patients had to be diagnosed with RA before the diagnosis of AF.
• They also assessed whether patients with RA were less likely to receive oral anticoagulants for stroke prevention within 3 months of AF diagnosis than those without RA.
• The median follow-up time was 2.5 years for patients with RA and 3.0 years for those without RA.
• The primary endpoint was ischemic stroke, which was identified through hospital admissions and visits.

TAKEAWAY:

• At 5 years, patients with both RA and AF showed a higher cumulative incidence of ischemic stroke than those with only AF (7.3% vs 5.0%).
• Among patients with AF, the risk of having a stroke was 25% higher in those with RA than in those without RA (adjusted hazard ratio, 1.25; 95% CI, 1.05-1.50).
• Patients with RA were also less likely to receive treatment with oral anticoagulants than those without RA, driven by concerns over potential interactions with RA medications, bleeding risk, or other factors (adjusted odds ratio, 0.88; 95% CI, 0.80-0.97). 

IN PRACTICE:

“Our study prompts preventive measures such as meticulous cardiovascular risk factor control among patients with RA and AF and raises the question whether the presence of RA should be taken into account when considering OAC [oral anticoagulant] treatment for AF patients,” the authors wrote.

SOURCE:

This study was led by Anne M. Kerola, MD, PhD, Helsinki University Hospital and University of Helsinki in Finland. It was published online in Rheumatology.

LIMITATIONS: 

This study lacked data on smoking, blood pressure measurements, alcohol use, and obesity, which may have affected the comprehensiveness of the findings. The study population was limited to Norway and may not be generalizable to other populations.

DISCLOSURES:

This study was supported by the Olav Thon Foundation, the Research Council of Norway, and the Foundation for Research in Rheumatology. Some authors received speaker fees, participated in advisory boards, served as consultants, or had other ties with some pharmaceutical companies and institutions.

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

TOPLINE: 

Patients with both rheumatoid arthritis (RA) and atrial fibrillation (AF) have a higher risk for ischemic stroke than those with only AF. They are also less likely to receive oral anticoagulant treatment, which may contribute to this increased stroke risk.

METHODOLOGY:

• Researchers conducted a registry-based retrospective cohort study using the Norwegian Cardio-Rheuma Register to evaluate the risk for ischemic stroke following the diagnosis of AF in patients with or without RA.
• They included 163,595 patients with newly diagnosed AF between 2010 and 2017, of whom 2750 had RA. Patients had to be diagnosed with RA before the diagnosis of AF.
• They also assessed whether patients with RA were less likely to receive oral anticoagulants for stroke prevention within 3 months of AF diagnosis than those without RA.
• The median follow-up time was 2.5 years for patients with RA and 3.0 years for those without RA.
• The primary endpoint was ischemic stroke, which was identified through hospital admissions and visits.

TAKEAWAY:

• At 5 years, patients with both RA and AF showed a higher cumulative incidence of ischemic stroke than those with only AF (7.3% vs 5.0%).
• Among patients with AF, the risk of having a stroke was 25% higher in those with RA than in those without RA (adjusted hazard ratio, 1.25; 95% CI, 1.05-1.50).
• Patients with RA were also less likely to receive treatment with oral anticoagulants than those without RA, driven by concerns over potential interactions with RA medications, bleeding risk, or other factors (adjusted odds ratio, 0.88; 95% CI, 0.80-0.97). 

IN PRACTICE:

“Our study prompts preventive measures such as meticulous cardiovascular risk factor control among patients with RA and AF and raises the question whether the presence of RA should be taken into account when considering OAC [oral anticoagulant] treatment for AF patients,” the authors wrote.

SOURCE:

This study was led by Anne M. Kerola, MD, PhD, Helsinki University Hospital and University of Helsinki in Finland. It was published online in Rheumatology.

LIMITATIONS: 

This study lacked data on smoking, blood pressure measurements, alcohol use, and obesity, which may have affected the comprehensiveness of the findings. The study population was limited to Norway and may not be generalizable to other populations.

DISCLOSURES:

This study was supported by the Olav Thon Foundation, the Research Council of Norway, and the Foundation for Research in Rheumatology. Some authors received speaker fees, participated in advisory boards, served as consultants, or had other ties with some pharmaceutical companies and institutions.

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

TOPLINE: 

Patients with both rheumatoid arthritis (RA) and atrial fibrillation (AF) have a higher risk for ischemic stroke than those with only AF. They are also less likely to receive oral anticoagulant treatment, which may contribute to this increased stroke risk.

METHODOLOGY:

• Researchers conducted a registry-based retrospective cohort study using the Norwegian Cardio-Rheuma Register to evaluate the risk for ischemic stroke following the diagnosis of AF in patients with or without RA.
• They included 163,595 patients with newly diagnosed AF between 2010 and 2017, of whom 2750 had RA. Patients had to be diagnosed with RA before the diagnosis of AF.
• They also assessed whether patients with RA were less likely to receive oral anticoagulants for stroke prevention within 3 months of AF diagnosis than those without RA.
• The median follow-up time was 2.5 years for patients with RA and 3.0 years for those without RA.
• The primary endpoint was ischemic stroke, which was identified through hospital admissions and visits.

TAKEAWAY:

• At 5 years, patients with both RA and AF showed a higher cumulative incidence of ischemic stroke than those with only AF (7.3% vs 5.0%).
• Among patients with AF, the risk of having a stroke was 25% higher in those with RA than in those without RA (adjusted hazard ratio, 1.25; 95% CI, 1.05-1.50).
• Patients with RA were also less likely to receive treatment with oral anticoagulants than those without RA, driven by concerns over potential interactions with RA medications, bleeding risk, or other factors (adjusted odds ratio, 0.88; 95% CI, 0.80-0.97). 

IN PRACTICE:

“Our study prompts preventive measures such as meticulous cardiovascular risk factor control among patients with RA and AF and raises the question whether the presence of RA should be taken into account when considering OAC [oral anticoagulant] treatment for AF patients,” the authors wrote.

SOURCE:

This study was led by Anne M. Kerola, MD, PhD, Helsinki University Hospital and University of Helsinki in Finland. It was published online in Rheumatology.

LIMITATIONS: 

This study lacked data on smoking, blood pressure measurements, alcohol use, and obesity, which may have affected the comprehensiveness of the findings. The study population was limited to Norway and may not be generalizable to other populations.

DISCLOSURES:

This study was supported by the Olav Thon Foundation, the Research Council of Norway, and the Foundation for Research in Rheumatology. Some authors received speaker fees, participated in advisory boards, served as consultants, or had other ties with some pharmaceutical companies and institutions.

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

This discussion was recorded on August 2, 2024. This transcript has been edited for clarity. 

Robert D. Glatter, MD: Today, we’ll be discussing the results of a new study published in The Journal of Emergency Medicine, looking at the incidence of delayed intracranial hemorrhage among older patients taking preinjury anticoagulants who present to the emergency department (ED) with blunt head trauma.

Joining me today is the lead author of the study, Dr. Richard Shih, professor of emergency medicine at Florida Atlantic University. Also joining me is Dr. Christina Shenvi, associate professor of emergency medicine at the University of North Carolina (UNC) Chapel Hill, with fellowship training in geriatric emergency medicine. 

Welcome to both of you.

Richard D. Shih, MD: Thanks, Rob. 

Christina L. Shenvi, MD, PhD, MBA: Thanks. Pleasure to be here. 
 

ICH Study Methodology

Dr. Glatter: It’s a pleasure to have you. Rich, this is a great study and targeted toward a population we see daily in the emergency department. I want you to describe your methodology, patient selection, and how you went about organizing your study to look at this important finding of delayed intracranial hemorrhage, especially in those on anticoagulants.

Dr. Shih: This all started for our research team when we first read the 2012 Annals of Emergency Medicine paper. The first author was Vincenzo Menditto, and he looked at a group of patients that had minor head injury, were anticoagulated, and had negative initial head CTs. 

There were about 100 patients, of which about 10 of them did not consent, but they hospitalized all these patients. These were anticoagulated, negative-first head CTs. They hospitalized the patients and then did a routine second CT at about 24 hours. They also followed them for a week, and it turned out a little over 7% of them had delayed head CT. 

We were wondering how many delayed intracranial hemorrhages we had missed because current practice for us was that, if patients had a good physical exam, their head CT was normal, and everything looked good, we would send them home.

Because of that, a number of people across the country wanted to verify those findings from the Menditto study. We tried to design a good study to answer that question. We happen to have a very large geriatric population in Florida, and our ED census is very high for age over 65, at nearly 60%. 

There are two Level I trauma centers in Palm Beach County. We included a second multicenter hospital, and we prospectively enrolled patients. We know the current state of practice is not to routinely do second CTs, so we followed these patients over time and followed their medical records to try to identify delayed bleeding. That’s how we set up our methodology.
 

Is It Safe to Discharge Patients With Trauma After 24 Hours?

Dr. Glatter: For the bulk of these patients with negative head CTs, it’s been my practice that when they’re stable and they look fine and there’s no other apparent, distracting painful trauma, injuries and so forth, they’re safe to discharge. 

The secondary outcome in your study is interesting: the need for neurosurgical intervention in terms of those with delayed intracranial hemorrhage.

Dr. Shih: I do believe that it’s certainly not the problem that Menditto described, which is 7%. There are two other prospective studies that have looked at this issue with delayed bleeding on anticoagulants. Both of these also showed a relatively low rate of delayed bleeding, which is between like 0.2% and 1.0%. In our study, it was 0.4%. 

The difference in the studies is that Menditto and colleagues routinely did 24-hour head CTs. They admitted everybody. For these other studies, routine head CT was not part of it. My bet is that there is a rate of delayed bleeding somewhere in between that seen in the Menditto study and that in all the other studies.

However, talking about significant intracranial hemorrhage, ones that perhaps need neurosurgery, I believe most of them are not significant. There’s some number that do occur, but the vast majority of those probably don’t need neurosurgery. We had 14 delayed bleeds out of 6000 patients with head trauma. One of them ended up requiring neurosurgery, so the answer is not zero, but I don’t think it’s 7% either. 

Dr. Glatter: Dr. Shenvi, I want to bring you into the conversation to talk about your experience at UNC, and how you run things in terms of older patients with blunt head trauma on preinjury anticoagulants.

Dr. Shenvi: Thanks, Rob. I remember when this paper came out showing this 7% rate of delayed bleeding and the question was, “Should we be admitting all these people?” Partly just from an overwhelming need for capacity that that would bring, it just wasn’t practical to say, “We’re going to admit every patient with a negative head CT to the hospital and rescan them.” That would be hundreds or thousands of patients each year in any given facility. 

The other thing is that delayed bleeds don’t always happen just in the first 24 hours. It’s not even a matter of bringing patients into observation for 24 hours, watching them, and rescanning them if they have symptoms. It can occur several days out. That never, in almost any institution that I know of, became standard practice. 

The way that it did change my care was to give good return precautions to patients, to make sure they have somebody with them to say, “Hey, sometimes you can have bleeding several days out after a fall, even though your CT scan here today looks perfect,” and to alert them that if they start having severe headaches, vomiting, or other symptoms of intracranial hemorrhage, that they should come back. 

I don’t think it ever became standard practice, and for good reason, because that was one study. The subsequent studies that Richard mentioned, pretty quickly on the heels of that initial one, showed a much lower rate of delayed ICH with the caveats that the methodology was different. 
 

Shift in Anticoagulants

Dr. Shenvi: One other big change from that original study, and now to Richard’s study, is the shift in anticoagulants. Back in the initial study you mentioned, it was all warfarin. We know from other studies looking at warfarin vs the direct oral anticoagulants (DOACs) that DOACs have lower rates of ICH after a head injury, lower rates of need for neurosurgical intervention, and lower rates of discharge to a skilled nursing facility after an intracranial hemorrhage.

Across the board, we know that the DOACs tend to do better. It’s difficult to compare newer studies because it’s a different medication. It did inform my practice to have an awareness of delayed intracranial hemorrhage so that I warn patients more proactively. 

Dr. Glatter: I haven’t seen a patient on warfarin in years. I don’t know if either of you have, but it’s all DOACs now unless there’s some other reason. That shift is quite apparent.

Dr. Shih: The problem with looking at delayed bleeding for DOACs vs warfarin is the numbers were so low. I think we had 13 people, and seven were in the no-anticoagulant group. The numbers are even lower, so it’s hard to say. 

I just wanted to comment on something that Dr. Shenvi said, and I pretty much agree with everything that she said. Anticoagulants and warfarin, and that Menditto study, have a carryover effect. People group DOACs with warfarin similarly. When a patient is brought in, the first thing they talk about with head trauma is, “Oh, they’re on an anticoagulant” or “They’re not on an anticoagulant.” It’s so ingrained.

I believe that, in emergency medicine, we’re pressed for space and time and we’re not as affected by that 24-hour observation. Maybe many of our surgeons will automatically admit those patients. 

I haven’t seen a guideline from the United States, but there are two international guidelines. One is from Austria from 2019, and one is from Scandinavia. Both recommended 24-hour observation if you’re on an anticoagulant.

There is a bit of controversy left over with that. Hopefully, as more and more of information, like in our study, comes out, people will be a little bit more clear about it. I don’t think there’s a need to routinely admit them. 

I do want to mention that the Menditto study had such a massive impact on everybody. They pointed out one subgroup (and it’s such a small number of patients). They had seven cases of delayed bleeding; four or five of them were within that 24 hours, and a couple were diagnosed later over the next couple days.

Of those seven people, four of them had international normalized ratios (INRs) greater than 3. Of those four patients, I’ve heard people talk about this and recommend, “Okay, that’s the subgroup I would admit.” There’s a toss-up with what to do with DOAC because it’s very hard to tell whether there’s an issue, whether there are problems with their dosing, and whatever. 

We actually recently looked at that. We have a much larger sample than four: close to 300 patients who were on warfarin. We looked at patients who had INRs below 3 and above 3, and we didn’t show a difference. We still don’t believe that warfarin is a big issue with delayed bleeding.
 

Should We Be Asking: ‘Are They on Blood Thinners?’

Dr. Shenvi: One of the interesting trends related to warfarin and the DOACs vs no anticoagulant is that as you mentioned, Dr Shih, the first question out of people’s mouths or the first piece of information emergency medical services gives you when they come in with a patient who’s had a head injury is, “Are they on blood thinners or not?”

Yet, the paradigm is shifting to say it’s not actually the blood thinners themselves that are giving older patients the higher risk for bleeding; it’s age and other comorbidities.

Certainly, if you’re on an anticoagulant and you start to bleed, your prognosis is much worse because the bleeding doesn’t stop. In terms of who has a bleeding event, there’s much less impact of anticoagulation than we used to think. That, in part, may be due to the change from warfarin to other medications.

Some of the experts I’ve talked to who have done the research on this have said, “Well, actually, warfarin was more of a marker for being much older and more frail, because it was primarily prescribed to older patients who have significant heart disease, atrial fibrillation, and so on.” It was more a marker for somebody who is at risk for an intracranial hemorrhage. There are many changes that have happened in the past 10 years with medications and also our understanding. 
 

Challenges in Patient Follow-up

Dr. Glatter: That’s a great point. One thing, Rich, I want to ask you about is in terms of your proxy outcome assessment. When you use that at 14 and 60 days with telephone follow-up and then chart review at 60 and 90 days (because, obviously, everyone can’t get another head CT or it’s difficult to follow patients up), did you find that worked out well in your prospective cohort study, in terms of using that as a proxy, so to speak? 

Dr. Shih: I would say to a certain extent. Unfortunately, we don’t have access to the patients to come back to follow up all of them, and there was obviously a large number of patients in our study. 

The next best thing was that we had dedicated research assistants calling all of the patients at 14 days and 60 days. I’ve certainly read research studies where, when they call them, they get 80%-90% follow-up, but we did not achieve that.

I don’t know if people are more inundated with spam phone calls now, or the older people are just afraid of picking up their phone sometimes with all the scams and so forth. I totally understand, but in all honesty, we only had about a 30%-35% follow-up using that follow-up pathway. 

Then the proxy pathway was to look at their charts at 60 and 90 days. Also, we looked at the Florida death registry, which is pretty good, and then finally, we had both Level I trauma centers in the county that we were in participating. It’s standard practice that if you have an intracranial hemorrhage at a non–Level I trauma center, you would be transferred to a Level I trauma center. That’s the protocol. I know that’s not followed 100% of the time, but that’s part of the proxy follow-up. You could criticize the study for not having closer to 90% actual contact, but that’s the best we could do. 

Dr. Glatter: I think that’s admirable. Using that paradigm of what you described certainly allows the reader to understand the difficulty in assessing patients that don’t get follow-up head CT, and hardly anyone does that, as we know.

To your point of having both Level I trauma centers in the county, that makes it pretty secure. If we’re going to do a study encompassing a similar type of regional aspect, it would be similar.

Dr. Shenvi: I think your proxies, to your credit, were as good as you can get. You can never get a 100% follow-up, but you really looked at all the different avenues by which patients might present, either in the death registry or a Level I center. Well done on that aspect.

 

Determining When to Admit Patients for Observation

Dr. Glatter: In terms of admissions: You admit a patient, then you hear back that this patient should not have been admitted because they had a negative head CT, but you put them in anyway in the sense of delayed bleeding happening or not happening.

It’s interesting. Maybe the insurers will start looking at this in some capacity, based on your study, that because it’s so infrequent that you see delayed bleeding, that admitting someone for any reason whatsoever would be declined. Do you see that being an issue? In other words, [do you see] this leading to a pattern in terms of the payers?

Dr. Shih: Certainly, you could interpret it that way, and that would be unfortunate. The [incidence of] delayed bleeding is definitely not zero. That’s the first thing. 

The second thing is that when you’re dealing with an older population, having some sense that they’re not doing well is an important contributor to trying to fully assess what’s going on — whether or not they have a bleed or whether they’re at risk for falling again and then hitting their head and causing a second bleed, and making sure they can do the activities of daily life. There really should be some room for a physician to say, “They just got here, and we don’t know him that well. There’s something that bothers me about this person” and have the ability to watch them for at least another 24 hours. That’s how I feel. 

Dr. Shenvi: In my location, it would be difficult to try to admit somebody purely for observation for delayed bleeding. I think we would get a lot of pushback on that. The reasons I might admit a patient after a fall with a negative head CT, though, are all the things that, Rob, you alluded to earlier — which are, what made them fall in the first place and were they unable to get up? 

I had this happen just this week. A patient who fell couldn’t get off the ground for 12 hours, and so now she’s dehydrated and delirious with slight rhabdomyolysis. Then you’re admitting them either for the sequelae of the fall that are not related to the intracranial hemorrhage, or the fact that they are so debilitated and deconditioned that they cannot take care of themselves. They need physical therapy. Often, we will have physical and occupational therapists come see them in the ED during business hours and help make an assessment of whether they are safe to go home or whether they fall again. That can give more evidence for the need for admission.

Dr. Glatter: To bring artificial intelligence into this discussion, algorithms that are out there that say, “Push a button and the patient’s safe for discharge.” Well, this argues for a clinical gestalt and a human being to make an assessment because you can use these predictive models, which are coming and they’re going to be here soon, and they already are in some sense. Again, we have to use clinical human judgment. 

Dr. Shih: I agree. 
 

Advice for Primary Care Physicians

Dr. Glatter: What return precautions do you discuss with patients who’ve had blunt head trauma that maybe had a head CT, or even didn’t? What are the main things we’re looking for?

Dr. Shenvi: What I usually tell people is if you start to have a worse headache, nausea or vomiting, any weakness in one area of your body, or vision changes, and if there’s a family member or friend there, I’ll say, “If you notice that they’re acting differently or seem confused, come back.”

Dr. Shih: I agree with what she said, and I’m also going to add one thing. The most important part is they are trying to prevent a subsequent fall. We know that when they’ve fallen and they present to the ED, they’re at even higher risk for falling and reinjuring themselves, and that’s a population that’s already at risk.

One of the secondary studies that we published out of this project was looking at follow-up with their primary care physicians, and there were two things that we wanted to address. The first was, how often did they do it? Then, when they did do it, did their primary care physicians try to address and prevent subsequent falls?

Both the answers are actually bad. Amazingly, just over like 60% followed up. 

In some of our subsequent research, because we’re in the midst of a randomized, controlled trial where we do a home visit, when we initially see these individuals that have fallen, they’ll schedule a home visit for us. Then a week or two later, when we schedule the home visit, many of them cancel because they think, Oh, that was a one-off and it’s not going to happen again. Part of the problem is the patients, because many of them believe that they just slipped and fell and it’s not going to happen again, or they’re not prone to it.

The second issue was when patients did go to a primary care physician, we have found that some primary care physicians believe that falling and injuring themselves is just part of the normal aging process. A percentage of them don’t go over assessment for fall risk or even initiate fall prevention treatments or programs. 

I try to take that time to tell them that this is very common in their age group, and believe it or not, a fall from standing is the way people really injure themselves, and there may be ways to prevent subsequent falls and injuries. 

Dr. Glatter: Absolutely. Do you find that their medications are a contributor in some sense? Say they’re antihypertensive, have issues of orthostasis, or a new medication was added in the last week. 

Dr. Shenvi: It’s all of the above. Sometimes it’s one thing, like they just started tamsulosin for their kidney stone, they stood up, they felt lightheaded, and they fell. Usually, it’s multifactorial with some changes in their gait, vision, balance, reflex time, and strength, plus the medications or the need for assistive devices. Maybe they can’t take care of their home as well as they used to and there are things on the floor. It’s really all of the above.
 

‘Harder to Unlearn Something Than to Learn It’

Dr. Glatter: Would either of you like to add any additional points to the discussion or add a few pearls? 

Dr. Shenvi: This just highlights the challenge of how it’s harder to unlearn something than to learn it, where one study that maybe wasn’t quite looking at what we needed to, or practice and prescribing patterns have changed, so it’s no longer really relevant. 

The things that we learned from that, or the fears that we instilled in our minds of, Uh oh, they could go home and have delayed bleeding, are much harder to unlearn, and it takes more studies to unlearn that idea than it did to actually put it into place. 

I’m glad that your team has done this much larger, prospective study and hopefully will reduce the concern about this entity. 

Dr. Shih: I appreciate that segue. It is amazing that, for paramedics and medical students, the first thing out of their mouth is, “Are they on an anticoagulant?”

In terms of the risk of developing an intracranial hemorrhage, I think it’s much less than the weight we’ve put on it before. However, I believe if they have a bleed, the bleeds are worse. It’s kind of a double-edged sword. It’s still an important factor, but it doesn’t come with the Oh my gosh, they’re on an anticoagulant that everybody thinks about.
 

No. 1 Cause of Traumatic Injury Is a Fall from Standing

Dr. Glatter: These are obviously ground-level falls in most patients and not motor vehicle crashes. That’s an important part in the population that you looked at that should be mentioned clearly. 

Dr. Shih: It’s astonishing. I’ve been a program director for over 20 years, and geriatrics is not well taught in the curriculum. It’s astonishing for many of our trainees and emergency physicians in general that the number-one cause for traumatic injury is a fall from standing.

Certainly, we get patients coming in the trauma center like a 95-year-old person who’s on a ladder putting up his Christmas lights. I’m like, oh my God. 

For the vast majority, it’s closer to 90%, but in our study, for the patients we looked at, it was 80% that fall from standing. That’s the mechanism that causes these bleeds and these major injuries. 

Dr. Shenvi: That’s reflective of what we see, so it’s good that that’s what you looked at also. 

Dr. Glatter: Absolutely. Well, thank you both. This has been a very informative discussion. I appreciate your time, and our readers will certainly benefit from your knowledge and expertise. Thank you again.

Dr. Glatter, assistant professor of emergency medicine at Zucker School of Medicine at Hofstra/Northwell in Hempstead, New York, is a medical adviser for this news organization. He disclosed having no relevant financial conflicts. Dr. Shih is professor of emergency medicine at the Charles E. Schmidt College of Medicine at Florida Atlantic University, Boca Raton. His current grant funding and area of research interest involves geriatric emergency department patients with head injury and fall-related injury. He disclosed receiving a research grant from The Florida Medical Malpractice Joint Underwriting Association Grant for Safety of Health Care Services). Dr. Shenvi, associate professor of emergency medicine at the University of North Carolina at Chapel Hill, disclosed ties with the American College of Emergency Physicians, Institute for Healthcare Improvement, AstraZeneca, and CurvaFix.

A version of this article appeared on Medscape.com.

This discussion was recorded on August 2, 2024. This transcript has been edited for clarity. 

Robert D. Glatter, MD: Today, we’ll be discussing the results of a new study published in The Journal of Emergency Medicine, looking at the incidence of delayed intracranial hemorrhage among older patients taking preinjury anticoagulants who present to the emergency department (ED) with blunt head trauma.

Joining me today is the lead author of the study, Dr. Richard Shih, professor of emergency medicine at Florida Atlantic University. Also joining me is Dr. Christina Shenvi, associate professor of emergency medicine at the University of North Carolina (UNC) Chapel Hill, with fellowship training in geriatric emergency medicine. 

Welcome to both of you.

Richard D. Shih, MD: Thanks, Rob. 

Christina L. Shenvi, MD, PhD, MBA: Thanks. Pleasure to be here. 
 

ICH Study Methodology

Dr. Glatter: It’s a pleasure to have you. Rich, this is a great study and targeted toward a population we see daily in the emergency department. I want you to describe your methodology, patient selection, and how you went about organizing your study to look at this important finding of delayed intracranial hemorrhage, especially in those on anticoagulants.

Dr. Shih: This all started for our research team when we first read the 2012 Annals of Emergency Medicine paper. The first author was Vincenzo Menditto, and he looked at a group of patients that had minor head injury, were anticoagulated, and had negative initial head CTs. 

There were about 100 patients, of which about 10 of them did not consent, but they hospitalized all these patients. These were anticoagulated, negative-first head CTs. They hospitalized the patients and then did a routine second CT at about 24 hours. They also followed them for a week, and it turned out a little over 7% of them had delayed head CT. 

We were wondering how many delayed intracranial hemorrhages we had missed because current practice for us was that, if patients had a good physical exam, their head CT was normal, and everything looked good, we would send them home.

Because of that, a number of people across the country wanted to verify those findings from the Menditto study. We tried to design a good study to answer that question. We happen to have a very large geriatric population in Florida, and our ED census is very high for age over 65, at nearly 60%. 

There are two Level I trauma centers in Palm Beach County. We included a second multicenter hospital, and we prospectively enrolled patients. We know the current state of practice is not to routinely do second CTs, so we followed these patients over time and followed their medical records to try to identify delayed bleeding. That’s how we set up our methodology.
 

Is It Safe to Discharge Patients With Trauma After 24 Hours?

Dr. Glatter: For the bulk of these patients with negative head CTs, it’s been my practice that when they’re stable and they look fine and there’s no other apparent, distracting painful trauma, injuries and so forth, they’re safe to discharge. 

The secondary outcome in your study is interesting: the need for neurosurgical intervention in terms of those with delayed intracranial hemorrhage.

Dr. Shih: I do believe that it’s certainly not the problem that Menditto described, which is 7%. There are two other prospective studies that have looked at this issue with delayed bleeding on anticoagulants. Both of these also showed a relatively low rate of delayed bleeding, which is between like 0.2% and 1.0%. In our study, it was 0.4%. 

The difference in the studies is that Menditto and colleagues routinely did 24-hour head CTs. They admitted everybody. For these other studies, routine head CT was not part of it. My bet is that there is a rate of delayed bleeding somewhere in between that seen in the Menditto study and that in all the other studies.

However, talking about significant intracranial hemorrhage, ones that perhaps need neurosurgery, I believe most of them are not significant. There’s some number that do occur, but the vast majority of those probably don’t need neurosurgery. We had 14 delayed bleeds out of 6000 patients with head trauma. One of them ended up requiring neurosurgery, so the answer is not zero, but I don’t think it’s 7% either. 

Dr. Glatter: Dr. Shenvi, I want to bring you into the conversation to talk about your experience at UNC, and how you run things in terms of older patients with blunt head trauma on preinjury anticoagulants.

Dr. Shenvi: Thanks, Rob. I remember when this paper came out showing this 7% rate of delayed bleeding and the question was, “Should we be admitting all these people?” Partly just from an overwhelming need for capacity that that would bring, it just wasn’t practical to say, “We’re going to admit every patient with a negative head CT to the hospital and rescan them.” That would be hundreds or thousands of patients each year in any given facility. 

The other thing is that delayed bleeds don’t always happen just in the first 24 hours. It’s not even a matter of bringing patients into observation for 24 hours, watching them, and rescanning them if they have symptoms. It can occur several days out. That never, in almost any institution that I know of, became standard practice. 

The way that it did change my care was to give good return precautions to patients, to make sure they have somebody with them to say, “Hey, sometimes you can have bleeding several days out after a fall, even though your CT scan here today looks perfect,” and to alert them that if they start having severe headaches, vomiting, or other symptoms of intracranial hemorrhage, that they should come back. 

I don’t think it ever became standard practice, and for good reason, because that was one study. The subsequent studies that Richard mentioned, pretty quickly on the heels of that initial one, showed a much lower rate of delayed ICH with the caveats that the methodology was different. 
 

Shift in Anticoagulants

Dr. Shenvi: One other big change from that original study, and now to Richard’s study, is the shift in anticoagulants. Back in the initial study you mentioned, it was all warfarin. We know from other studies looking at warfarin vs the direct oral anticoagulants (DOACs) that DOACs have lower rates of ICH after a head injury, lower rates of need for neurosurgical intervention, and lower rates of discharge to a skilled nursing facility after an intracranial hemorrhage.

Across the board, we know that the DOACs tend to do better. It’s difficult to compare newer studies because it’s a different medication. It did inform my practice to have an awareness of delayed intracranial hemorrhage so that I warn patients more proactively. 

Dr. Glatter: I haven’t seen a patient on warfarin in years. I don’t know if either of you have, but it’s all DOACs now unless there’s some other reason. That shift is quite apparent.

Dr. Shih: The problem with looking at delayed bleeding for DOACs vs warfarin is the numbers were so low. I think we had 13 people, and seven were in the no-anticoagulant group. The numbers are even lower, so it’s hard to say. 

I just wanted to comment on something that Dr. Shenvi said, and I pretty much agree with everything that she said. Anticoagulants and warfarin, and that Menditto study, have a carryover effect. People group DOACs with warfarin similarly. When a patient is brought in, the first thing they talk about with head trauma is, “Oh, they’re on an anticoagulant” or “They’re not on an anticoagulant.” It’s so ingrained.

I believe that, in emergency medicine, we’re pressed for space and time and we’re not as affected by that 24-hour observation. Maybe many of our surgeons will automatically admit those patients. 

I haven’t seen a guideline from the United States, but there are two international guidelines. One is from Austria from 2019, and one is from Scandinavia. Both recommended 24-hour observation if you’re on an anticoagulant.

There is a bit of controversy left over with that. Hopefully, as more and more of information, like in our study, comes out, people will be a little bit more clear about it. I don’t think there’s a need to routinely admit them. 

I do want to mention that the Menditto study had such a massive impact on everybody. They pointed out one subgroup (and it’s such a small number of patients). They had seven cases of delayed bleeding; four or five of them were within that 24 hours, and a couple were diagnosed later over the next couple days.

Of those seven people, four of them had international normalized ratios (INRs) greater than 3. Of those four patients, I’ve heard people talk about this and recommend, “Okay, that’s the subgroup I would admit.” There’s a toss-up with what to do with DOAC because it’s very hard to tell whether there’s an issue, whether there are problems with their dosing, and whatever. 

We actually recently looked at that. We have a much larger sample than four: close to 300 patients who were on warfarin. We looked at patients who had INRs below 3 and above 3, and we didn’t show a difference. We still don’t believe that warfarin is a big issue with delayed bleeding.
 

Should We Be Asking: ‘Are They on Blood Thinners?’

Dr. Shenvi: One of the interesting trends related to warfarin and the DOACs vs no anticoagulant is that as you mentioned, Dr Shih, the first question out of people’s mouths or the first piece of information emergency medical services gives you when they come in with a patient who’s had a head injury is, “Are they on blood thinners or not?”

Yet, the paradigm is shifting to say it’s not actually the blood thinners themselves that are giving older patients the higher risk for bleeding; it’s age and other comorbidities.

Certainly, if you’re on an anticoagulant and you start to bleed, your prognosis is much worse because the bleeding doesn’t stop. In terms of who has a bleeding event, there’s much less impact of anticoagulation than we used to think. That, in part, may be due to the change from warfarin to other medications.

Some of the experts I’ve talked to who have done the research on this have said, “Well, actually, warfarin was more of a marker for being much older and more frail, because it was primarily prescribed to older patients who have significant heart disease, atrial fibrillation, and so on.” It was more a marker for somebody who is at risk for an intracranial hemorrhage. There are many changes that have happened in the past 10 years with medications and also our understanding. 
 

Challenges in Patient Follow-up

Dr. Glatter: That’s a great point. One thing, Rich, I want to ask you about is in terms of your proxy outcome assessment. When you use that at 14 and 60 days with telephone follow-up and then chart review at 60 and 90 days (because, obviously, everyone can’t get another head CT or it’s difficult to follow patients up), did you find that worked out well in your prospective cohort study, in terms of using that as a proxy, so to speak? 

Dr. Shih: I would say to a certain extent. Unfortunately, we don’t have access to the patients to come back to follow up all of them, and there was obviously a large number of patients in our study. 

The next best thing was that we had dedicated research assistants calling all of the patients at 14 days and 60 days. I’ve certainly read research studies where, when they call them, they get 80%-90% follow-up, but we did not achieve that.

I don’t know if people are more inundated with spam phone calls now, or the older people are just afraid of picking up their phone sometimes with all the scams and so forth. I totally understand, but in all honesty, we only had about a 30%-35% follow-up using that follow-up pathway. 

Then the proxy pathway was to look at their charts at 60 and 90 days. Also, we looked at the Florida death registry, which is pretty good, and then finally, we had both Level I trauma centers in the county that we were in participating. It’s standard practice that if you have an intracranial hemorrhage at a non–Level I trauma center, you would be transferred to a Level I trauma center. That’s the protocol. I know that’s not followed 100% of the time, but that’s part of the proxy follow-up. You could criticize the study for not having closer to 90% actual contact, but that’s the best we could do. 

Dr. Glatter: I think that’s admirable. Using that paradigm of what you described certainly allows the reader to understand the difficulty in assessing patients that don’t get follow-up head CT, and hardly anyone does that, as we know.

To your point of having both Level I trauma centers in the county, that makes it pretty secure. If we’re going to do a study encompassing a similar type of regional aspect, it would be similar.

Dr. Shenvi: I think your proxies, to your credit, were as good as you can get. You can never get a 100% follow-up, but you really looked at all the different avenues by which patients might present, either in the death registry or a Level I center. Well done on that aspect.

 

Determining When to Admit Patients for Observation

Dr. Glatter: In terms of admissions: You admit a patient, then you hear back that this patient should not have been admitted because they had a negative head CT, but you put them in anyway in the sense of delayed bleeding happening or not happening.

It’s interesting. Maybe the insurers will start looking at this in some capacity, based on your study, that because it’s so infrequent that you see delayed bleeding, that admitting someone for any reason whatsoever would be declined. Do you see that being an issue? In other words, [do you see] this leading to a pattern in terms of the payers?

Dr. Shih: Certainly, you could interpret it that way, and that would be unfortunate. The [incidence of] delayed bleeding is definitely not zero. That’s the first thing. 

The second thing is that when you’re dealing with an older population, having some sense that they’re not doing well is an important contributor to trying to fully assess what’s going on — whether or not they have a bleed or whether they’re at risk for falling again and then hitting their head and causing a second bleed, and making sure they can do the activities of daily life. There really should be some room for a physician to say, “They just got here, and we don’t know him that well. There’s something that bothers me about this person” and have the ability to watch them for at least another 24 hours. That’s how I feel. 

Dr. Shenvi: In my location, it would be difficult to try to admit somebody purely for observation for delayed bleeding. I think we would get a lot of pushback on that. The reasons I might admit a patient after a fall with a negative head CT, though, are all the things that, Rob, you alluded to earlier — which are, what made them fall in the first place and were they unable to get up? 

I had this happen just this week. A patient who fell couldn’t get off the ground for 12 hours, and so now she’s dehydrated and delirious with slight rhabdomyolysis. Then you’re admitting them either for the sequelae of the fall that are not related to the intracranial hemorrhage, or the fact that they are so debilitated and deconditioned that they cannot take care of themselves. They need physical therapy. Often, we will have physical and occupational therapists come see them in the ED during business hours and help make an assessment of whether they are safe to go home or whether they fall again. That can give more evidence for the need for admission.

Dr. Glatter: To bring artificial intelligence into this discussion, algorithms that are out there that say, “Push a button and the patient’s safe for discharge.” Well, this argues for a clinical gestalt and a human being to make an assessment because you can use these predictive models, which are coming and they’re going to be here soon, and they already are in some sense. Again, we have to use clinical human judgment. 

Dr. Shih: I agree. 
 

Advice for Primary Care Physicians

Dr. Glatter: What return precautions do you discuss with patients who’ve had blunt head trauma that maybe had a head CT, or even didn’t? What are the main things we’re looking for?

Dr. Shenvi: What I usually tell people is if you start to have a worse headache, nausea or vomiting, any weakness in one area of your body, or vision changes, and if there’s a family member or friend there, I’ll say, “If you notice that they’re acting differently or seem confused, come back.”

Dr. Shih: I agree with what she said, and I’m also going to add one thing. The most important part is they are trying to prevent a subsequent fall. We know that when they’ve fallen and they present to the ED, they’re at even higher risk for falling and reinjuring themselves, and that’s a population that’s already at risk.

One of the secondary studies that we published out of this project was looking at follow-up with their primary care physicians, and there were two things that we wanted to address. The first was, how often did they do it? Then, when they did do it, did their primary care physicians try to address and prevent subsequent falls?

Both the answers are actually bad. Amazingly, just over like 60% followed up. 

In some of our subsequent research, because we’re in the midst of a randomized, controlled trial where we do a home visit, when we initially see these individuals that have fallen, they’ll schedule a home visit for us. Then a week or two later, when we schedule the home visit, many of them cancel because they think, Oh, that was a one-off and it’s not going to happen again. Part of the problem is the patients, because many of them believe that they just slipped and fell and it’s not going to happen again, or they’re not prone to it.

The second issue was when patients did go to a primary care physician, we have found that some primary care physicians believe that falling and injuring themselves is just part of the normal aging process. A percentage of them don’t go over assessment for fall risk or even initiate fall prevention treatments or programs. 

I try to take that time to tell them that this is very common in their age group, and believe it or not, a fall from standing is the way people really injure themselves, and there may be ways to prevent subsequent falls and injuries. 

Dr. Glatter: Absolutely. Do you find that their medications are a contributor in some sense? Say they’re antihypertensive, have issues of orthostasis, or a new medication was added in the last week. 

Dr. Shenvi: It’s all of the above. Sometimes it’s one thing, like they just started tamsulosin for their kidney stone, they stood up, they felt lightheaded, and they fell. Usually, it’s multifactorial with some changes in their gait, vision, balance, reflex time, and strength, plus the medications or the need for assistive devices. Maybe they can’t take care of their home as well as they used to and there are things on the floor. It’s really all of the above.
 

‘Harder to Unlearn Something Than to Learn It’

Dr. Glatter: Would either of you like to add any additional points to the discussion or add a few pearls? 

Dr. Shenvi: This just highlights the challenge of how it’s harder to unlearn something than to learn it, where one study that maybe wasn’t quite looking at what we needed to, or practice and prescribing patterns have changed, so it’s no longer really relevant. 

The things that we learned from that, or the fears that we instilled in our minds of, Uh oh, they could go home and have delayed bleeding, are much harder to unlearn, and it takes more studies to unlearn that idea than it did to actually put it into place. 

I’m glad that your team has done this much larger, prospective study and hopefully will reduce the concern about this entity. 

Dr. Shih: I appreciate that segue. It is amazing that, for paramedics and medical students, the first thing out of their mouth is, “Are they on an anticoagulant?”

In terms of the risk of developing an intracranial hemorrhage, I think it’s much less than the weight we’ve put on it before. However, I believe if they have a bleed, the bleeds are worse. It’s kind of a double-edged sword. It’s still an important factor, but it doesn’t come with the Oh my gosh, they’re on an anticoagulant that everybody thinks about.
 

No. 1 Cause of Traumatic Injury Is a Fall from Standing

Dr. Glatter: These are obviously ground-level falls in most patients and not motor vehicle crashes. That’s an important part in the population that you looked at that should be mentioned clearly. 

Dr. Shih: It’s astonishing. I’ve been a program director for over 20 years, and geriatrics is not well taught in the curriculum. It’s astonishing for many of our trainees and emergency physicians in general that the number-one cause for traumatic injury is a fall from standing.

Certainly, we get patients coming in the trauma center like a 95-year-old person who’s on a ladder putting up his Christmas lights. I’m like, oh my God. 

For the vast majority, it’s closer to 90%, but in our study, for the patients we looked at, it was 80% that fall from standing. That’s the mechanism that causes these bleeds and these major injuries. 

Dr. Shenvi: That’s reflective of what we see, so it’s good that that’s what you looked at also. 

Dr. Glatter: Absolutely. Well, thank you both. This has been a very informative discussion. I appreciate your time, and our readers will certainly benefit from your knowledge and expertise. Thank you again.

Dr. Glatter, assistant professor of emergency medicine at Zucker School of Medicine at Hofstra/Northwell in Hempstead, New York, is a medical adviser for this news organization. He disclosed having no relevant financial conflicts. Dr. Shih is professor of emergency medicine at the Charles E. Schmidt College of Medicine at Florida Atlantic University, Boca Raton. His current grant funding and area of research interest involves geriatric emergency department patients with head injury and fall-related injury. He disclosed receiving a research grant from The Florida Medical Malpractice Joint Underwriting Association Grant for Safety of Health Care Services). Dr. Shenvi, associate professor of emergency medicine at the University of North Carolina at Chapel Hill, disclosed ties with the American College of Emergency Physicians, Institute for Healthcare Improvement, AstraZeneca, and CurvaFix.

A version of this article appeared on Medscape.com.

This discussion was recorded on August 2, 2024. This transcript has been edited for clarity. 

Robert D. Glatter, MD: Today, we’ll be discussing the results of a new study published in The Journal of Emergency Medicine, looking at the incidence of delayed intracranial hemorrhage among older patients taking preinjury anticoagulants who present to the emergency department (ED) with blunt head trauma.

Joining me today is the lead author of the study, Dr. Richard Shih, professor of emergency medicine at Florida Atlantic University. Also joining me is Dr. Christina Shenvi, associate professor of emergency medicine at the University of North Carolina (UNC) Chapel Hill, with fellowship training in geriatric emergency medicine. 

Welcome to both of you.

Richard D. Shih, MD: Thanks, Rob. 

Christina L. Shenvi, MD, PhD, MBA: Thanks. Pleasure to be here. 
 

ICH Study Methodology

Dr. Glatter: It’s a pleasure to have you. Rich, this is a great study and targeted toward a population we see daily in the emergency department. I want you to describe your methodology, patient selection, and how you went about organizing your study to look at this important finding of delayed intracranial hemorrhage, especially in those on anticoagulants.

Dr. Shih: This all started for our research team when we first read the 2012 Annals of Emergency Medicine paper. The first author was Vincenzo Menditto, and he looked at a group of patients that had minor head injury, were anticoagulated, and had negative initial head CTs. 

There were about 100 patients, of which about 10 of them did not consent, but they hospitalized all these patients. These were anticoagulated, negative-first head CTs. They hospitalized the patients and then did a routine second CT at about 24 hours. They also followed them for a week, and it turned out a little over 7% of them had delayed head CT. 

We were wondering how many delayed intracranial hemorrhages we had missed because current practice for us was that, if patients had a good physical exam, their head CT was normal, and everything looked good, we would send them home.

Because of that, a number of people across the country wanted to verify those findings from the Menditto study. We tried to design a good study to answer that question. We happen to have a very large geriatric population in Florida, and our ED census is very high for age over 65, at nearly 60%. 

There are two Level I trauma centers in Palm Beach County. We included a second multicenter hospital, and we prospectively enrolled patients. We know the current state of practice is not to routinely do second CTs, so we followed these patients over time and followed their medical records to try to identify delayed bleeding. That’s how we set up our methodology.
 

Is It Safe to Discharge Patients With Trauma After 24 Hours?

Dr. Glatter: For the bulk of these patients with negative head CTs, it’s been my practice that when they’re stable and they look fine and there’s no other apparent, distracting painful trauma, injuries and so forth, they’re safe to discharge. 

The secondary outcome in your study is interesting: the need for neurosurgical intervention in terms of those with delayed intracranial hemorrhage.

Dr. Shih: I do believe that it’s certainly not the problem that Menditto described, which is 7%. There are two other prospective studies that have looked at this issue with delayed bleeding on anticoagulants. Both of these also showed a relatively low rate of delayed bleeding, which is between like 0.2% and 1.0%. In our study, it was 0.4%. 

The difference in the studies is that Menditto and colleagues routinely did 24-hour head CTs. They admitted everybody. For these other studies, routine head CT was not part of it. My bet is that there is a rate of delayed bleeding somewhere in between that seen in the Menditto study and that in all the other studies.

However, talking about significant intracranial hemorrhage, ones that perhaps need neurosurgery, I believe most of them are not significant. There’s some number that do occur, but the vast majority of those probably don’t need neurosurgery. We had 14 delayed bleeds out of 6000 patients with head trauma. One of them ended up requiring neurosurgery, so the answer is not zero, but I don’t think it’s 7% either. 

Dr. Glatter: Dr. Shenvi, I want to bring you into the conversation to talk about your experience at UNC, and how you run things in terms of older patients with blunt head trauma on preinjury anticoagulants.

Dr. Shenvi: Thanks, Rob. I remember when this paper came out showing this 7% rate of delayed bleeding and the question was, “Should we be admitting all these people?” Partly just from an overwhelming need for capacity that that would bring, it just wasn’t practical to say, “We’re going to admit every patient with a negative head CT to the hospital and rescan them.” That would be hundreds or thousands of patients each year in any given facility. 

The other thing is that delayed bleeds don’t always happen just in the first 24 hours. It’s not even a matter of bringing patients into observation for 24 hours, watching them, and rescanning them if they have symptoms. It can occur several days out. That never, in almost any institution that I know of, became standard practice. 

The way that it did change my care was to give good return precautions to patients, to make sure they have somebody with them to say, “Hey, sometimes you can have bleeding several days out after a fall, even though your CT scan here today looks perfect,” and to alert them that if they start having severe headaches, vomiting, or other symptoms of intracranial hemorrhage, that they should come back. 

I don’t think it ever became standard practice, and for good reason, because that was one study. The subsequent studies that Richard mentioned, pretty quickly on the heels of that initial one, showed a much lower rate of delayed ICH with the caveats that the methodology was different. 
 

Shift in Anticoagulants

Dr. Shenvi: One other big change from that original study, and now to Richard’s study, is the shift in anticoagulants. Back in the initial study you mentioned, it was all warfarin. We know from other studies looking at warfarin vs the direct oral anticoagulants (DOACs) that DOACs have lower rates of ICH after a head injury, lower rates of need for neurosurgical intervention, and lower rates of discharge to a skilled nursing facility after an intracranial hemorrhage.

Across the board, we know that the DOACs tend to do better. It’s difficult to compare newer studies because it’s a different medication. It did inform my practice to have an awareness of delayed intracranial hemorrhage so that I warn patients more proactively. 

Dr. Glatter: I haven’t seen a patient on warfarin in years. I don’t know if either of you have, but it’s all DOACs now unless there’s some other reason. That shift is quite apparent.

Dr. Shih: The problem with looking at delayed bleeding for DOACs vs warfarin is the numbers were so low. I think we had 13 people, and seven were in the no-anticoagulant group. The numbers are even lower, so it’s hard to say. 

I just wanted to comment on something that Dr. Shenvi said, and I pretty much agree with everything that she said. Anticoagulants and warfarin, and that Menditto study, have a carryover effect. People group DOACs with warfarin similarly. When a patient is brought in, the first thing they talk about with head trauma is, “Oh, they’re on an anticoagulant” or “They’re not on an anticoagulant.” It’s so ingrained.

I believe that, in emergency medicine, we’re pressed for space and time and we’re not as affected by that 24-hour observation. Maybe many of our surgeons will automatically admit those patients. 

I haven’t seen a guideline from the United States, but there are two international guidelines. One is from Austria from 2019, and one is from Scandinavia. Both recommended 24-hour observation if you’re on an anticoagulant.

There is a bit of controversy left over with that. Hopefully, as more and more of information, like in our study, comes out, people will be a little bit more clear about it. I don’t think there’s a need to routinely admit them. 

I do want to mention that the Menditto study had such a massive impact on everybody. They pointed out one subgroup (and it’s such a small number of patients). They had seven cases of delayed bleeding; four or five of them were within that 24 hours, and a couple were diagnosed later over the next couple days.

Of those seven people, four of them had international normalized ratios (INRs) greater than 3. Of those four patients, I’ve heard people talk about this and recommend, “Okay, that’s the subgroup I would admit.” There’s a toss-up with what to do with DOAC because it’s very hard to tell whether there’s an issue, whether there are problems with their dosing, and whatever. 

We actually recently looked at that. We have a much larger sample than four: close to 300 patients who were on warfarin. We looked at patients who had INRs below 3 and above 3, and we didn’t show a difference. We still don’t believe that warfarin is a big issue with delayed bleeding.
 

Should We Be Asking: ‘Are They on Blood Thinners?’

Dr. Shenvi: One of the interesting trends related to warfarin and the DOACs vs no anticoagulant is that as you mentioned, Dr Shih, the first question out of people’s mouths or the first piece of information emergency medical services gives you when they come in with a patient who’s had a head injury is, “Are they on blood thinners or not?”

Yet, the paradigm is shifting to say it’s not actually the blood thinners themselves that are giving older patients the higher risk for bleeding; it’s age and other comorbidities.

Certainly, if you’re on an anticoagulant and you start to bleed, your prognosis is much worse because the bleeding doesn’t stop. In terms of who has a bleeding event, there’s much less impact of anticoagulation than we used to think. That, in part, may be due to the change from warfarin to other medications.

Some of the experts I’ve talked to who have done the research on this have said, “Well, actually, warfarin was more of a marker for being much older and more frail, because it was primarily prescribed to older patients who have significant heart disease, atrial fibrillation, and so on.” It was more a marker for somebody who is at risk for an intracranial hemorrhage. There are many changes that have happened in the past 10 years with medications and also our understanding. 
 

Challenges in Patient Follow-up

Dr. Glatter: That’s a great point. One thing, Rich, I want to ask you about is in terms of your proxy outcome assessment. When you use that at 14 and 60 days with telephone follow-up and then chart review at 60 and 90 days (because, obviously, everyone can’t get another head CT or it’s difficult to follow patients up), did you find that worked out well in your prospective cohort study, in terms of using that as a proxy, so to speak? 

Dr. Shih: I would say to a certain extent. Unfortunately, we don’t have access to the patients to come back to follow up all of them, and there was obviously a large number of patients in our study. 

The next best thing was that we had dedicated research assistants calling all of the patients at 14 days and 60 days. I’ve certainly read research studies where, when they call them, they get 80%-90% follow-up, but we did not achieve that.

I don’t know if people are more inundated with spam phone calls now, or the older people are just afraid of picking up their phone sometimes with all the scams and so forth. I totally understand, but in all honesty, we only had about a 30%-35% follow-up using that follow-up pathway. 

Then the proxy pathway was to look at their charts at 60 and 90 days. Also, we looked at the Florida death registry, which is pretty good, and then finally, we had both Level I trauma centers in the county that we were in participating. It’s standard practice that if you have an intracranial hemorrhage at a non–Level I trauma center, you would be transferred to a Level I trauma center. That’s the protocol. I know that’s not followed 100% of the time, but that’s part of the proxy follow-up. You could criticize the study for not having closer to 90% actual contact, but that’s the best we could do. 

Dr. Glatter: I think that’s admirable. Using that paradigm of what you described certainly allows the reader to understand the difficulty in assessing patients that don’t get follow-up head CT, and hardly anyone does that, as we know.

To your point of having both Level I trauma centers in the county, that makes it pretty secure. If we’re going to do a study encompassing a similar type of regional aspect, it would be similar.

Dr. Shenvi: I think your proxies, to your credit, were as good as you can get. You can never get a 100% follow-up, but you really looked at all the different avenues by which patients might present, either in the death registry or a Level I center. Well done on that aspect.

 

Determining When to Admit Patients for Observation

Dr. Glatter: In terms of admissions: You admit a patient, then you hear back that this patient should not have been admitted because they had a negative head CT, but you put them in anyway in the sense of delayed bleeding happening or not happening.

It’s interesting. Maybe the insurers will start looking at this in some capacity, based on your study, that because it’s so infrequent that you see delayed bleeding, that admitting someone for any reason whatsoever would be declined. Do you see that being an issue? In other words, [do you see] this leading to a pattern in terms of the payers?

Dr. Shih: Certainly, you could interpret it that way, and that would be unfortunate. The [incidence of] delayed bleeding is definitely not zero. That’s the first thing. 

The second thing is that when you’re dealing with an older population, having some sense that they’re not doing well is an important contributor to trying to fully assess what’s going on — whether or not they have a bleed or whether they’re at risk for falling again and then hitting their head and causing a second bleed, and making sure they can do the activities of daily life. There really should be some room for a physician to say, “They just got here, and we don’t know him that well. There’s something that bothers me about this person” and have the ability to watch them for at least another 24 hours. That’s how I feel. 

Dr. Shenvi: In my location, it would be difficult to try to admit somebody purely for observation for delayed bleeding. I think we would get a lot of pushback on that. The reasons I might admit a patient after a fall with a negative head CT, though, are all the things that, Rob, you alluded to earlier — which are, what made them fall in the first place and were they unable to get up? 

I had this happen just this week. A patient who fell couldn’t get off the ground for 12 hours, and so now she’s dehydrated and delirious with slight rhabdomyolysis. Then you’re admitting them either for the sequelae of the fall that are not related to the intracranial hemorrhage, or the fact that they are so debilitated and deconditioned that they cannot take care of themselves. They need physical therapy. Often, we will have physical and occupational therapists come see them in the ED during business hours and help make an assessment of whether they are safe to go home or whether they fall again. That can give more evidence for the need for admission.

Dr. Glatter: To bring artificial intelligence into this discussion, algorithms that are out there that say, “Push a button and the patient’s safe for discharge.” Well, this argues for a clinical gestalt and a human being to make an assessment because you can use these predictive models, which are coming and they’re going to be here soon, and they already are in some sense. Again, we have to use clinical human judgment. 

Dr. Shih: I agree. 
 

Advice for Primary Care Physicians

Dr. Glatter: What return precautions do you discuss with patients who’ve had blunt head trauma that maybe had a head CT, or even didn’t? What are the main things we’re looking for?

Dr. Shenvi: What I usually tell people is if you start to have a worse headache, nausea or vomiting, any weakness in one area of your body, or vision changes, and if there’s a family member or friend there, I’ll say, “If you notice that they’re acting differently or seem confused, come back.”

Dr. Shih: I agree with what she said, and I’m also going to add one thing. The most important part is they are trying to prevent a subsequent fall. We know that when they’ve fallen and they present to the ED, they’re at even higher risk for falling and reinjuring themselves, and that’s a population that’s already at risk.

One of the secondary studies that we published out of this project was looking at follow-up with their primary care physicians, and there were two things that we wanted to address. The first was, how often did they do it? Then, when they did do it, did their primary care physicians try to address and prevent subsequent falls?

Both the answers are actually bad. Amazingly, just over like 60% followed up. 

In some of our subsequent research, because we’re in the midst of a randomized, controlled trial where we do a home visit, when we initially see these individuals that have fallen, they’ll schedule a home visit for us. Then a week or two later, when we schedule the home visit, many of them cancel because they think, Oh, that was a one-off and it’s not going to happen again. Part of the problem is the patients, because many of them believe that they just slipped and fell and it’s not going to happen again, or they’re not prone to it.

The second issue was when patients did go to a primary care physician, we have found that some primary care physicians believe that falling and injuring themselves is just part of the normal aging process. A percentage of them don’t go over assessment for fall risk or even initiate fall prevention treatments or programs. 

I try to take that time to tell them that this is very common in their age group, and believe it or not, a fall from standing is the way people really injure themselves, and there may be ways to prevent subsequent falls and injuries. 

Dr. Glatter: Absolutely. Do you find that their medications are a contributor in some sense? Say they’re antihypertensive, have issues of orthostasis, or a new medication was added in the last week. 

Dr. Shenvi: It’s all of the above. Sometimes it’s one thing, like they just started tamsulosin for their kidney stone, they stood up, they felt lightheaded, and they fell. Usually, it’s multifactorial with some changes in their gait, vision, balance, reflex time, and strength, plus the medications or the need for assistive devices. Maybe they can’t take care of their home as well as they used to and there are things on the floor. It’s really all of the above.
 

‘Harder to Unlearn Something Than to Learn It’

Dr. Glatter: Would either of you like to add any additional points to the discussion or add a few pearls? 

Dr. Shenvi: This just highlights the challenge of how it’s harder to unlearn something than to learn it, where one study that maybe wasn’t quite looking at what we needed to, or practice and prescribing patterns have changed, so it’s no longer really relevant. 

The things that we learned from that, or the fears that we instilled in our minds of, Uh oh, they could go home and have delayed bleeding, are much harder to unlearn, and it takes more studies to unlearn that idea than it did to actually put it into place. 

I’m glad that your team has done this much larger, prospective study and hopefully will reduce the concern about this entity. 

Dr. Shih: I appreciate that segue. It is amazing that, for paramedics and medical students, the first thing out of their mouth is, “Are they on an anticoagulant?”

In terms of the risk of developing an intracranial hemorrhage, I think it’s much less than the weight we’ve put on it before. However, I believe if they have a bleed, the bleeds are worse. It’s kind of a double-edged sword. It’s still an important factor, but it doesn’t come with the Oh my gosh, they’re on an anticoagulant that everybody thinks about.
 

No. 1 Cause of Traumatic Injury Is a Fall from Standing

Dr. Glatter: These are obviously ground-level falls in most patients and not motor vehicle crashes. That’s an important part in the population that you looked at that should be mentioned clearly. 

Dr. Shih: It’s astonishing. I’ve been a program director for over 20 years, and geriatrics is not well taught in the curriculum. It’s astonishing for many of our trainees and emergency physicians in general that the number-one cause for traumatic injury is a fall from standing.

Certainly, we get patients coming in the trauma center like a 95-year-old person who’s on a ladder putting up his Christmas lights. I’m like, oh my God. 

For the vast majority, it’s closer to 90%, but in our study, for the patients we looked at, it was 80% that fall from standing. That’s the mechanism that causes these bleeds and these major injuries. 

Dr. Shenvi: That’s reflective of what we see, so it’s good that that’s what you looked at also. 

Dr. Glatter: Absolutely. Well, thank you both. This has been a very informative discussion. I appreciate your time, and our readers will certainly benefit from your knowledge and expertise. Thank you again.

Dr. Glatter, assistant professor of emergency medicine at Zucker School of Medicine at Hofstra/Northwell in Hempstead, New York, is a medical adviser for this news organization. He disclosed having no relevant financial conflicts. Dr. Shih is professor of emergency medicine at the Charles E. Schmidt College of Medicine at Florida Atlantic University, Boca Raton. His current grant funding and area of research interest involves geriatric emergency department patients with head injury and fall-related injury. He disclosed receiving a research grant from The Florida Medical Malpractice Joint Underwriting Association Grant for Safety of Health Care Services). Dr. Shenvi, associate professor of emergency medicine at the University of North Carolina at Chapel Hill, disclosed ties with the American College of Emergency Physicians, Institute for Healthcare Improvement, AstraZeneca, and CurvaFix.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Hi. I’m Art Caplan. I’m at the Division of Medical Ethics at the NYU Grossman School of Medicine in New York City. 

We have many debates and arguments that are swirling around about the out-of-control costs of Medicare. Many people are arguing we’ve got to trim it and cut back, and many people note that we can’t just go on and on with that kind of expenditure.

People look around for savings. Rightly, we can’t go on with the prices that we’re paying. No system could. We’ll bankrupt ourselves if we don’t drive prices down. 

There’s another area that is driving up cost where, despite the fact that Medicare doesn’t pay for it, we could capture resources and hopefully shift them back to things like Medicare coverage or the insurance of other efficacious procedures. That area is the wellness industry. 

I looked up a number recently, and I was shocked to see that worldwide, $1.8 trillion is being spent on wellness, including billions in the US. Again, Medicare doesn’t pay for that. That’s money coming out of people’s pockets that we could hopefully aim at the payment of things that we know work, not seeing the money drain out to cover bunk, nonsense, and charlatanism.

Does any or most of this stuff work? Do anything? Help anybody? No. We are spending money on charlatans and quacks. The US Food and Drug Administration (FDA), which you might think is the agency that could step in and start to get rid of some of this nonsense, is just too overwhelmed trying to track drugs, devices, and vaccines to give much attention to the wellness industry.

What am I talking about specifically? I’m talking about everything from gut probiotics that are sold in sodas to probiotic facial creams and the Goop industry of Gwyneth Paltrow, where you have people buying things like wellness mats or vaginal eggs that are supposed to maintain gynecologic health.

We’re talking about things like PEMF, or pulse electronic magnetic fields, where you buy a machine and expose yourself to mild magnetic pulses. I went online to look them up, and the machines cost $5000-$50,000. There’s no evidence that it works. By the way, the machines are not only out there as being sold for pain relief and many other things to humans, but also they’re being sold for your pets.

That industry is completely out of control. Wellness interventions, whether it’s transcranial magnetism or all manner of supplements that are sold in health food stores, over and over again, we see a world in which wellness is promoted but no data are introduced to show that any of it helps, works, or does anybody any good.

It may not be all that harmful, but it’s certainly financially toxic to many people who end up spending good amounts of money using these things. I think doctors need to ask patients if they are using any of these things, particularly if they have chronic conditions. They’re likely, many of them, to be seduced by online advertisement to get involved with this stuff because it’s preventive or it’ll help treat some condition that they have. 

The industry is out of control. We’re trying to figure out how to spend money on things we know work in medicine, and yet we continue to tolerate bunk, nonsense, quackery, and charlatanism, just letting it grow and grow and grow in terms of cost.

That’s money that could go elsewhere. That is money that is being taken out of the pockets of patients. They’re doing things that may even delay medical treatment, which won’t really help them, and they are doing things that perhaps might even interfere with medical care that really is known to be beneficial.

I think it’s time to push for more money for the FDA to regulate the wellness side. I think it’s time for the Federal Trade Commission to go after ads that promise health benefits. I think it’s time to have some honest conversations with patients: What are you using? What are you doing? Tell me about it, and here’s why I think you could probably spend your money in a better way. 
 

Dr. Caplan, director, Division of Medical Ethics, New York University Langone Medical Center, New York, disclosed ties with Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position). He serves as a contributing author and adviser for Medscape.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Hi. I’m Art Caplan. I’m at the Division of Medical Ethics at the NYU Grossman School of Medicine in New York City. 

We have many debates and arguments that are swirling around about the out-of-control costs of Medicare. Many people are arguing we’ve got to trim it and cut back, and many people note that we can’t just go on and on with that kind of expenditure.

People look around for savings. Rightly, we can’t go on with the prices that we’re paying. No system could. We’ll bankrupt ourselves if we don’t drive prices down. 

There’s another area that is driving up cost where, despite the fact that Medicare doesn’t pay for it, we could capture resources and hopefully shift them back to things like Medicare coverage or the insurance of other efficacious procedures. That area is the wellness industry. 

I looked up a number recently, and I was shocked to see that worldwide, $1.8 trillion is being spent on wellness, including billions in the US. Again, Medicare doesn’t pay for that. That’s money coming out of people’s pockets that we could hopefully aim at the payment of things that we know work, not seeing the money drain out to cover bunk, nonsense, and charlatanism.

Does any or most of this stuff work? Do anything? Help anybody? No. We are spending money on charlatans and quacks. The US Food and Drug Administration (FDA), which you might think is the agency that could step in and start to get rid of some of this nonsense, is just too overwhelmed trying to track drugs, devices, and vaccines to give much attention to the wellness industry.

What am I talking about specifically? I’m talking about everything from gut probiotics that are sold in sodas to probiotic facial creams and the Goop industry of Gwyneth Paltrow, where you have people buying things like wellness mats or vaginal eggs that are supposed to maintain gynecologic health.

We’re talking about things like PEMF, or pulse electronic magnetic fields, where you buy a machine and expose yourself to mild magnetic pulses. I went online to look them up, and the machines cost $5000-$50,000. There’s no evidence that it works. By the way, the machines are not only out there as being sold for pain relief and many other things to humans, but also they’re being sold for your pets.

That industry is completely out of control. Wellness interventions, whether it’s transcranial magnetism or all manner of supplements that are sold in health food stores, over and over again, we see a world in which wellness is promoted but no data are introduced to show that any of it helps, works, or does anybody any good.

It may not be all that harmful, but it’s certainly financially toxic to many people who end up spending good amounts of money using these things. I think doctors need to ask patients if they are using any of these things, particularly if they have chronic conditions. They’re likely, many of them, to be seduced by online advertisement to get involved with this stuff because it’s preventive or it’ll help treat some condition that they have. 

The industry is out of control. We’re trying to figure out how to spend money on things we know work in medicine, and yet we continue to tolerate bunk, nonsense, quackery, and charlatanism, just letting it grow and grow and grow in terms of cost.

That’s money that could go elsewhere. That is money that is being taken out of the pockets of patients. They’re doing things that may even delay medical treatment, which won’t really help them, and they are doing things that perhaps might even interfere with medical care that really is known to be beneficial.

I think it’s time to push for more money for the FDA to regulate the wellness side. I think it’s time for the Federal Trade Commission to go after ads that promise health benefits. I think it’s time to have some honest conversations with patients: What are you using? What are you doing? Tell me about it, and here’s why I think you could probably spend your money in a better way. 
 

Dr. Caplan, director, Division of Medical Ethics, New York University Langone Medical Center, New York, disclosed ties with Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position). He serves as a contributing author and adviser for Medscape.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Hi. I’m Art Caplan. I’m at the Division of Medical Ethics at the NYU Grossman School of Medicine in New York City. 

We have many debates and arguments that are swirling around about the out-of-control costs of Medicare. Many people are arguing we’ve got to trim it and cut back, and many people note that we can’t just go on and on with that kind of expenditure.

People look around for savings. Rightly, we can’t go on with the prices that we’re paying. No system could. We’ll bankrupt ourselves if we don’t drive prices down. 

There’s another area that is driving up cost where, despite the fact that Medicare doesn’t pay for it, we could capture resources and hopefully shift them back to things like Medicare coverage or the insurance of other efficacious procedures. That area is the wellness industry. 

I looked up a number recently, and I was shocked to see that worldwide, $1.8 trillion is being spent on wellness, including billions in the US. Again, Medicare doesn’t pay for that. That’s money coming out of people’s pockets that we could hopefully aim at the payment of things that we know work, not seeing the money drain out to cover bunk, nonsense, and charlatanism.

Does any or most of this stuff work? Do anything? Help anybody? No. We are spending money on charlatans and quacks. The US Food and Drug Administration (FDA), which you might think is the agency that could step in and start to get rid of some of this nonsense, is just too overwhelmed trying to track drugs, devices, and vaccines to give much attention to the wellness industry.

What am I talking about specifically? I’m talking about everything from gut probiotics that are sold in sodas to probiotic facial creams and the Goop industry of Gwyneth Paltrow, where you have people buying things like wellness mats or vaginal eggs that are supposed to maintain gynecologic health.

We’re talking about things like PEMF, or pulse electronic magnetic fields, where you buy a machine and expose yourself to mild magnetic pulses. I went online to look them up, and the machines cost $5000-$50,000. There’s no evidence that it works. By the way, the machines are not only out there as being sold for pain relief and many other things to humans, but also they’re being sold for your pets.

That industry is completely out of control. Wellness interventions, whether it’s transcranial magnetism or all manner of supplements that are sold in health food stores, over and over again, we see a world in which wellness is promoted but no data are introduced to show that any of it helps, works, or does anybody any good.

It may not be all that harmful, but it’s certainly financially toxic to many people who end up spending good amounts of money using these things. I think doctors need to ask patients if they are using any of these things, particularly if they have chronic conditions. They’re likely, many of them, to be seduced by online advertisement to get involved with this stuff because it’s preventive or it’ll help treat some condition that they have. 

The industry is out of control. We’re trying to figure out how to spend money on things we know work in medicine, and yet we continue to tolerate bunk, nonsense, quackery, and charlatanism, just letting it grow and grow and grow in terms of cost.

That’s money that could go elsewhere. That is money that is being taken out of the pockets of patients. They’re doing things that may even delay medical treatment, which won’t really help them, and they are doing things that perhaps might even interfere with medical care that really is known to be beneficial.

I think it’s time to push for more money for the FDA to regulate the wellness side. I think it’s time for the Federal Trade Commission to go after ads that promise health benefits. I think it’s time to have some honest conversations with patients: What are you using? What are you doing? Tell me about it, and here’s why I think you could probably spend your money in a better way. 
 

Dr. Caplan, director, Division of Medical Ethics, New York University Langone Medical Center, New York, disclosed ties with Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position). He serves as a contributing author and adviser for Medscape.

A version of this article appeared on Medscape.com.

The ABYSS trial found that interruption of beta-blocker therapy in patients after myocardial infarction (MI) was not noninferior to continuing the drugs. 

I will argue why I think it is okay to stop beta-blockers after MI — despite this conclusion. The results of ABYSS are, in fact, similar to REDUCE-AMI, which compared beta-blocker use or nonuse immediately after MI, and found no difference in a composite endpoint of death or MI. 

Translation of the ABYSS trial results to patient care is a case where we must look past the paper’s abstract and conclusions. The key problem is the authors’ choice of primary endpoint, which obscures the correct clinical answer.
 

The ABYSS Trial

ABYSS investigators randomly assigned nearly 3700 patients who had MI and were prescribed a beta-blocker to either continue (control arm) or stop (active arm) the drug at 1 year. 

Patients had to have a left ventricular ejection fraction (LVEF) at least 40%; the median was 60%. 

The composite primary endpoint included death, MI, stroke, or hospitalization for any cardiovascular reason. ABYSS authors chose a noninferiority design. The assumption must have been that the interruption arm offered an easier option for patients — eg, fewer pills. 

Over 3 years, a primary endpoint occurred in 23.8% of the interruption group vs 21.1% in the continuation group. 

In ABYSS, the noninferiority margin was set at a 3% absolute risk increase. The 2.7% absolute risk increase had an upper bound of the 95% CI (worst case) of 5.5% leading to the not-noninferior conclusion (5.5% exceeds the noninferiority margins). 

More simply stated, the primary outcome event rate was higher in the interruption arm. 
 

Does This Mean we Should Continue Beta-Blockers in Post-MI Patients?

This led some to conclude that we should continue beta-blockers. I disagree. To properly interpret the ABYSS trial, you must consider trial procedures, components of the primary endpoint, and then compare ABYSS with REDUCE-AMI. 

It’s also reasonable to have extremely pessimistic prior beliefs about post-MI beta-blockade because the evidence establishing benefit comes from trials conducted before urgent revascularization became the standard therapy. 

ABYSS was a pragmatic open-label trial. The core problem with this design is that one of the components of the primary outcome (hospitalization for cardiovascular reasons) requires clinical judgment — and is therefore susceptible to bias, particularly in an open-label trial. 

This becomes apparent when we look at the components of the primary outcome in the two arms of the trial (interrupt vs continue): 

• For death, the rates were 4.1 and 4.0%
• For MI, the rates were 2.5 and 2.4%
• For stroke, the rates were 1.0% in both arms
• For CV hospitalization, the rates were 18.9% vs 16.6%

The higher rate CV hospitalization alone drove the results of ABYSS. Death, MI, and stroke rates were nearly identical. 

The most common reason for admission to the hospital in this category was for angiography. In fact, the rate of angiography was 2.3% higher in the interruption arm — identical to the rate increase in the CV hospitalization component of the primary endpoint. 

The results of ABYSS, therefore, were driven by higher rates of angiography in the interrupt arm. 

You need not imply malfeasance to speculate that patients who had their beta-blocker stopped might be treated differently regarding hospital admissions or angiography than those who stayed on beta-blockers. Researchers from Imperial College London called such a bias in unblinded trials “subtraction anxiety and faith healing.”

Had the ABYSS investigators chosen the simpler, less bias-prone endpoints of death, MI, or stroke, their results would have been the same as REDUCE-AMI. 
 

My Final Two Conclusions

I would conclude that interruption of beta-blockers at 1 year vs continuation in post-MI patients did not lead to an increase in death, MI, or stroke. 

ABYSS, therefore, is consistent with REDUCE-AMI. Taken together, along with the pessimistic priors, these are important findings because they allow us to stop a medicine and reduce the work of being a patient. 

My second conclusion concerns ways of knowing in medicine. I’ve long felt that randomized controlled trials (RCTs) are the best way to sort out causation. This idea led me to the believe that medicine should have more RCTs rather than follow expert opinion or therapeutic fashion. 

I’ve now modified my love of RCTs — a little. The ABYSS trial is yet another example of the need to be super careful with their design.

Something as seemingly simple as choosing what to measure can alter the way clinicians interpret and use the data. 

So, let’s have (slightly) more trials, but we should be really careful in their design. Slow and careful is the best way to practice medicine. And it’s surely the best way to do research as well.

Dr. Mandrola, clinical electrophysiologist, Baptist Medical Associates, Louisville, Kentucky, has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

The ABYSS trial found that interruption of beta-blocker therapy in patients after myocardial infarction (MI) was not noninferior to continuing the drugs. 

I will argue why I think it is okay to stop beta-blockers after MI — despite this conclusion. The results of ABYSS are, in fact, similar to REDUCE-AMI, which compared beta-blocker use or nonuse immediately after MI, and found no difference in a composite endpoint of death or MI. 

Translation of the ABYSS trial results to patient care is a case where we must look past the paper’s abstract and conclusions. The key problem is the authors’ choice of primary endpoint, which obscures the correct clinical answer.
 

The ABYSS Trial

ABYSS investigators randomly assigned nearly 3700 patients who had MI and were prescribed a beta-blocker to either continue (control arm) or stop (active arm) the drug at 1 year. 

Patients had to have a left ventricular ejection fraction (LVEF) at least 40%; the median was 60%. 

The composite primary endpoint included death, MI, stroke, or hospitalization for any cardiovascular reason. ABYSS authors chose a noninferiority design. The assumption must have been that the interruption arm offered an easier option for patients — eg, fewer pills. 

Over 3 years, a primary endpoint occurred in 23.8% of the interruption group vs 21.1% in the continuation group. 

In ABYSS, the noninferiority margin was set at a 3% absolute risk increase. The 2.7% absolute risk increase had an upper bound of the 95% CI (worst case) of 5.5% leading to the not-noninferior conclusion (5.5% exceeds the noninferiority margins). 

More simply stated, the primary outcome event rate was higher in the interruption arm. 
 

Does This Mean we Should Continue Beta-Blockers in Post-MI Patients?

This led some to conclude that we should continue beta-blockers. I disagree. To properly interpret the ABYSS trial, you must consider trial procedures, components of the primary endpoint, and then compare ABYSS with REDUCE-AMI. 

It’s also reasonable to have extremely pessimistic prior beliefs about post-MI beta-blockade because the evidence establishing benefit comes from trials conducted before urgent revascularization became the standard therapy. 

ABYSS was a pragmatic open-label trial. The core problem with this design is that one of the components of the primary outcome (hospitalization for cardiovascular reasons) requires clinical judgment — and is therefore susceptible to bias, particularly in an open-label trial. 

This becomes apparent when we look at the components of the primary outcome in the two arms of the trial (interrupt vs continue): 

• For death, the rates were 4.1 and 4.0%
• For MI, the rates were 2.5 and 2.4%
• For stroke, the rates were 1.0% in both arms
• For CV hospitalization, the rates were 18.9% vs 16.6%

The higher rate CV hospitalization alone drove the results of ABYSS. Death, MI, and stroke rates were nearly identical. 

The most common reason for admission to the hospital in this category was for angiography. In fact, the rate of angiography was 2.3% higher in the interruption arm — identical to the rate increase in the CV hospitalization component of the primary endpoint. 

The results of ABYSS, therefore, were driven by higher rates of angiography in the interrupt arm. 

You need not imply malfeasance to speculate that patients who had their beta-blocker stopped might be treated differently regarding hospital admissions or angiography than those who stayed on beta-blockers. Researchers from Imperial College London called such a bias in unblinded trials “subtraction anxiety and faith healing.”

Had the ABYSS investigators chosen the simpler, less bias-prone endpoints of death, MI, or stroke, their results would have been the same as REDUCE-AMI. 
 

My Final Two Conclusions

I would conclude that interruption of beta-blockers at 1 year vs continuation in post-MI patients did not lead to an increase in death, MI, or stroke. 

ABYSS, therefore, is consistent with REDUCE-AMI. Taken together, along with the pessimistic priors, these are important findings because they allow us to stop a medicine and reduce the work of being a patient. 

My second conclusion concerns ways of knowing in medicine. I’ve long felt that randomized controlled trials (RCTs) are the best way to sort out causation. This idea led me to the believe that medicine should have more RCTs rather than follow expert opinion or therapeutic fashion. 

I’ve now modified my love of RCTs — a little. The ABYSS trial is yet another example of the need to be super careful with their design.

Something as seemingly simple as choosing what to measure can alter the way clinicians interpret and use the data. 

So, let’s have (slightly) more trials, but we should be really careful in their design. Slow and careful is the best way to practice medicine. And it’s surely the best way to do research as well.

Dr. Mandrola, clinical electrophysiologist, Baptist Medical Associates, Louisville, Kentucky, has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

The ABYSS trial found that interruption of beta-blocker therapy in patients after myocardial infarction (MI) was not noninferior to continuing the drugs. 

I will argue why I think it is okay to stop beta-blockers after MI — despite this conclusion. The results of ABYSS are, in fact, similar to REDUCE-AMI, which compared beta-blocker use or nonuse immediately after MI, and found no difference in a composite endpoint of death or MI. 

Translation of the ABYSS trial results to patient care is a case where we must look past the paper’s abstract and conclusions. The key problem is the authors’ choice of primary endpoint, which obscures the correct clinical answer.
 

The ABYSS Trial

ABYSS investigators randomly assigned nearly 3700 patients who had MI and were prescribed a beta-blocker to either continue (control arm) or stop (active arm) the drug at 1 year. 

Patients had to have a left ventricular ejection fraction (LVEF) at least 40%; the median was 60%. 

The composite primary endpoint included death, MI, stroke, or hospitalization for any cardiovascular reason. ABYSS authors chose a noninferiority design. The assumption must have been that the interruption arm offered an easier option for patients — eg, fewer pills. 

Over 3 years, a primary endpoint occurred in 23.8% of the interruption group vs 21.1% in the continuation group. 

In ABYSS, the noninferiority margin was set at a 3% absolute risk increase. The 2.7% absolute risk increase had an upper bound of the 95% CI (worst case) of 5.5% leading to the not-noninferior conclusion (5.5% exceeds the noninferiority margins). 

More simply stated, the primary outcome event rate was higher in the interruption arm. 
 

Does This Mean we Should Continue Beta-Blockers in Post-MI Patients?

This led some to conclude that we should continue beta-blockers. I disagree. To properly interpret the ABYSS trial, you must consider trial procedures, components of the primary endpoint, and then compare ABYSS with REDUCE-AMI. 

It’s also reasonable to have extremely pessimistic prior beliefs about post-MI beta-blockade because the evidence establishing benefit comes from trials conducted before urgent revascularization became the standard therapy. 

ABYSS was a pragmatic open-label trial. The core problem with this design is that one of the components of the primary outcome (hospitalization for cardiovascular reasons) requires clinical judgment — and is therefore susceptible to bias, particularly in an open-label trial. 

This becomes apparent when we look at the components of the primary outcome in the two arms of the trial (interrupt vs continue): 

• For death, the rates were 4.1 and 4.0%
• For MI, the rates were 2.5 and 2.4%
• For stroke, the rates were 1.0% in both arms
• For CV hospitalization, the rates were 18.9% vs 16.6%

The higher rate CV hospitalization alone drove the results of ABYSS. Death, MI, and stroke rates were nearly identical. 

The most common reason for admission to the hospital in this category was for angiography. In fact, the rate of angiography was 2.3% higher in the interruption arm — identical to the rate increase in the CV hospitalization component of the primary endpoint. 

The results of ABYSS, therefore, were driven by higher rates of angiography in the interrupt arm. 

You need not imply malfeasance to speculate that patients who had their beta-blocker stopped might be treated differently regarding hospital admissions or angiography than those who stayed on beta-blockers. Researchers from Imperial College London called such a bias in unblinded trials “subtraction anxiety and faith healing.”

Had the ABYSS investigators chosen the simpler, less bias-prone endpoints of death, MI, or stroke, their results would have been the same as REDUCE-AMI. 
 

My Final Two Conclusions

I would conclude that interruption of beta-blockers at 1 year vs continuation in post-MI patients did not lead to an increase in death, MI, or stroke. 

ABYSS, therefore, is consistent with REDUCE-AMI. Taken together, along with the pessimistic priors, these are important findings because they allow us to stop a medicine and reduce the work of being a patient. 

My second conclusion concerns ways of knowing in medicine. I’ve long felt that randomized controlled trials (RCTs) are the best way to sort out causation. This idea led me to the believe that medicine should have more RCTs rather than follow expert opinion or therapeutic fashion. 

I’ve now modified my love of RCTs — a little. The ABYSS trial is yet another example of the need to be super careful with their design.

Something as seemingly simple as choosing what to measure can alter the way clinicians interpret and use the data. 

So, let’s have (slightly) more trials, but we should be really careful in their design. Slow and careful is the best way to practice medicine. And it’s surely the best way to do research as well.

Dr. Mandrola, clinical electrophysiologist, Baptist Medical Associates, Louisville, Kentucky, has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

LONDON — It may not be advisable for patients with a history of myocardial infarction and preserved left ventricular function to discontinue long-term beta-blocker therapy, warn investigators.

In the randomized ABYSS trial, although there was no difference in death, MI, or stroke between patients who discontinued and those who continued taking beta-blockers, those who stopped taking the drugs had a higher rate of cardiovascular hospitalization.

Discontinuation was also associated with an increase in blood pressure and heart rate, without any improvement in quality of life.

“We thought we would be able to withdraw beta-blockers safely and that this would result in improved quality of life, but our trial results suggest this is not the case,” said lead investigator Johanne Silvain, MD, PhD, from Pitié-Salpêtrière University Hospital in Paris, who presented the ABYSS findings here at the European Society of Cardiology (ESC) Congress. 

The results, which were simultaneously published online in The New England Journal of Medicine, call into question current guidelines, which suggest that beta-blockers may be discontinued after 1 year in certain patient groups.

Beta-blockers have long been considered the standard of care for patients after MI, but trials showing the benefit of these drugs were conducted before the modern era of myocardial reperfusion and pharmacotherapy, which have led to sharp decreases in the risk for heart failure and for death after MI, Dr. Silvain explained. 

This has led to questions about the add-on benefits of lifelong beta-blocker treatment for patients with MI and a preserved left ventricular ejection fraction and no other primary indication for beta-blocker therapy.
 

The ABYSS Trial

To explore this issue, the open-label, non-inferiority ABYSS trial randomly assigned 3698 patients with a history of MI to the discontinuation or continuation of beta-blocker treatment. All study participants had a left ventricular ejection fraction of at least 40%, were receiving long-term beta-blocker treatment, and had experienced no cardiovascular event in the previous 6 months. 

At a median follow-up of 3 years, the primary endpoint — a composite of death, MI, stroke, and hospitalization for cardiovascular reasons — occurred more often in the discontinuation group than in the continuation group (23.8% vs 21.1%; hazard ratio, 1.16; 95% CI, 1.01-1.33). This did not meet the criteria for non-inferiority of discontinuation, compared with continuation, of beta-blocker therapy (P for non-inferiority = .44).

The difference in event rates between the two groups was driven by cardiovascular hospitalizations, which occurred more often in the discontinuation group than in the continuation group (18.9% vs 16.6%).

Other key results showed that there was no difference in quality of life between the two groups.

However, 6 months after randomization, there were increases in blood pressure and heart rate in the discontinuation group. Systolic blood pressure increased by 3.7 mm Hg and diastolic blood pressure increased by 3.9 mm Hg. Resting heart rate increased by 9.8 beats per minute.

“We were not able to show the non-inferiority of stopping beta-blockers in terms of cardiovascular events, [but we] showed a safety signal with this strategy of an increase in blood pressure and heart rate, with no improvement in quality of life,” Dr. Sylvain said.

“While recent guidelines suggest it may be reasonable to stop beta-blockers in this population, after these results, I will not be stopping these drugs if they are being well tolerated,” he said.

Sylvain said he was surprised that there was not an improvement in quality of life in the group that discontinued beta-blockers. “We are always told that beta-blockers have many side effects, so we expected to see an improvement in quality of life in the patients who stopped these drugs.”

One possible reason for the lack of improvement in quality of life is that the trial participants had been taking beta-blockers for several years. “We may have, therefore, selected patients who tolerate these drugs quite well. Those who had tolerance issues had probably already stopped taking them,” he explained.

In addition, the patient population had relatively high quality-of-life scores at baseline. “They were well treated and the therapies they were taking were well tolerated, so maybe it is difficult to improve quality of life further,” he said.
 

The REDUCE-AMI Trial

The ABYSS results appear at first to differ from results from the recent REDUCE-AMI trial, which failed to show the superiority of beta-blocker therapy, compared with no beta-blocker therapy, in acute MI patients with preserved ejection fraction.

But the REDUCE-AMI primary endpoint was a composite of death from any cause or new myocardial infarction; it did not include cardiovascular hospitalization, which was the main driver of the difference in outcomes in the ABYSS study, Dr. Sylvain pointed out.

“We showed an increase in coronary cases of hospitalization with stopping beta-blockers, and you have to remember that beta-blockers were developed to reduce coronary disease,” he said.
 

‘Slightly Inconclusive’

Jane Armitage, MBBS, University of Oxford, England, the ABYSS discussant for the ESC HOTLINE session, pointed out some limitations of the study, which led her to report that the result was “slightly inconclusive.” 

The open-label design may have allowed some bias regarding the cardiovascular hospitalization endpoint, she said.

“The decision whether to admit a patient to [the] hospital is somewhat subjective and could be influenced by a physician’s knowledge of treatment allocation. That is why, ideally, we prefer blinded trials. I think there are questions there,” she explained.

She also questioned whether the non-inferiority margin could have been increased, given the higher-than-expected event rate.

More data on this issue will come from several trials that are currently ongoing, Dr. Armitage said.

The ABYSS and REDUCE-AMI trials together suggest that it is safe, with respect to serious cardiac events, to stop beta-blocker treatment in MI patients with preserved ejection fraction, writes Tomas Jernberg, MD, PhD, from the Karolinska Institute in Stockholm, Sweden, in an accompanying editorial.

However, “because of the anti-ischemic effects of beta-blockers, an interruption may increase the risk of recurrent angina and the need for rehospitalization,” he adds.

“It is prudent to wait for the results of additional ongoing trials of beta-blockers involving patients with MI and a preserved left ventricular ejection fraction before definitively updating guidelines,” Dr. Jernberg concludes.

The ABYSS trial was funded by the French Ministry of Health and the ACTION Study Group. Dr. Sylvain, Dr. Armitage, and Dr. Jernberg report no relevant financial relationships.

A version of this article appeared on Medscape.com.

LONDON — It may not be advisable for patients with a history of myocardial infarction and preserved left ventricular function to discontinue long-term beta-blocker therapy, warn investigators.

In the randomized ABYSS trial, although there was no difference in death, MI, or stroke between patients who discontinued and those who continued taking beta-blockers, those who stopped taking the drugs had a higher rate of cardiovascular hospitalization.

Discontinuation was also associated with an increase in blood pressure and heart rate, without any improvement in quality of life.

“We thought we would be able to withdraw beta-blockers safely and that this would result in improved quality of life, but our trial results suggest this is not the case,” said lead investigator Johanne Silvain, MD, PhD, from Pitié-Salpêtrière University Hospital in Paris, who presented the ABYSS findings here at the European Society of Cardiology (ESC) Congress. 

The results, which were simultaneously published online in The New England Journal of Medicine, call into question current guidelines, which suggest that beta-blockers may be discontinued after 1 year in certain patient groups.

Beta-blockers have long been considered the standard of care for patients after MI, but trials showing the benefit of these drugs were conducted before the modern era of myocardial reperfusion and pharmacotherapy, which have led to sharp decreases in the risk for heart failure and for death after MI, Dr. Silvain explained. 

This has led to questions about the add-on benefits of lifelong beta-blocker treatment for patients with MI and a preserved left ventricular ejection fraction and no other primary indication for beta-blocker therapy.
 

The ABYSS Trial

To explore this issue, the open-label, non-inferiority ABYSS trial randomly assigned 3698 patients with a history of MI to the discontinuation or continuation of beta-blocker treatment. All study participants had a left ventricular ejection fraction of at least 40%, were receiving long-term beta-blocker treatment, and had experienced no cardiovascular event in the previous 6 months. 

At a median follow-up of 3 years, the primary endpoint — a composite of death, MI, stroke, and hospitalization for cardiovascular reasons — occurred more often in the discontinuation group than in the continuation group (23.8% vs 21.1%; hazard ratio, 1.16; 95% CI, 1.01-1.33). This did not meet the criteria for non-inferiority of discontinuation, compared with continuation, of beta-blocker therapy (P for non-inferiority = .44).

The difference in event rates between the two groups was driven by cardiovascular hospitalizations, which occurred more often in the discontinuation group than in the continuation group (18.9% vs 16.6%).

Other key results showed that there was no difference in quality of life between the two groups.

However, 6 months after randomization, there were increases in blood pressure and heart rate in the discontinuation group. Systolic blood pressure increased by 3.7 mm Hg and diastolic blood pressure increased by 3.9 mm Hg. Resting heart rate increased by 9.8 beats per minute.

“We were not able to show the non-inferiority of stopping beta-blockers in terms of cardiovascular events, [but we] showed a safety signal with this strategy of an increase in blood pressure and heart rate, with no improvement in quality of life,” Dr. Sylvain said.

“While recent guidelines suggest it may be reasonable to stop beta-blockers in this population, after these results, I will not be stopping these drugs if they are being well tolerated,” he said.

Sylvain said he was surprised that there was not an improvement in quality of life in the group that discontinued beta-blockers. “We are always told that beta-blockers have many side effects, so we expected to see an improvement in quality of life in the patients who stopped these drugs.”

One possible reason for the lack of improvement in quality of life is that the trial participants had been taking beta-blockers for several years. “We may have, therefore, selected patients who tolerate these drugs quite well. Those who had tolerance issues had probably already stopped taking them,” he explained.

In addition, the patient population had relatively high quality-of-life scores at baseline. “They were well treated and the therapies they were taking were well tolerated, so maybe it is difficult to improve quality of life further,” he said.
 

The REDUCE-AMI Trial

The ABYSS results appear at first to differ from results from the recent REDUCE-AMI trial, which failed to show the superiority of beta-blocker therapy, compared with no beta-blocker therapy, in acute MI patients with preserved ejection fraction.

But the REDUCE-AMI primary endpoint was a composite of death from any cause or new myocardial infarction; it did not include cardiovascular hospitalization, which was the main driver of the difference in outcomes in the ABYSS study, Dr. Sylvain pointed out.

“We showed an increase in coronary cases of hospitalization with stopping beta-blockers, and you have to remember that beta-blockers were developed to reduce coronary disease,” he said.
 

‘Slightly Inconclusive’

Jane Armitage, MBBS, University of Oxford, England, the ABYSS discussant for the ESC HOTLINE session, pointed out some limitations of the study, which led her to report that the result was “slightly inconclusive.” 

The open-label design may have allowed some bias regarding the cardiovascular hospitalization endpoint, she said.

“The decision whether to admit a patient to [the] hospital is somewhat subjective and could be influenced by a physician’s knowledge of treatment allocation. That is why, ideally, we prefer blinded trials. I think there are questions there,” she explained.

She also questioned whether the non-inferiority margin could have been increased, given the higher-than-expected event rate.

More data on this issue will come from several trials that are currently ongoing, Dr. Armitage said.

The ABYSS and REDUCE-AMI trials together suggest that it is safe, with respect to serious cardiac events, to stop beta-blocker treatment in MI patients with preserved ejection fraction, writes Tomas Jernberg, MD, PhD, from the Karolinska Institute in Stockholm, Sweden, in an accompanying editorial.

However, “because of the anti-ischemic effects of beta-blockers, an interruption may increase the risk of recurrent angina and the need for rehospitalization,” he adds.

“It is prudent to wait for the results of additional ongoing trials of beta-blockers involving patients with MI and a preserved left ventricular ejection fraction before definitively updating guidelines,” Dr. Jernberg concludes.

The ABYSS trial was funded by the French Ministry of Health and the ACTION Study Group. Dr. Sylvain, Dr. Armitage, and Dr. Jernberg report no relevant financial relationships.

A version of this article appeared on Medscape.com.

LONDON — It may not be advisable for patients with a history of myocardial infarction and preserved left ventricular function to discontinue long-term beta-blocker therapy, warn investigators.

In the randomized ABYSS trial, although there was no difference in death, MI, or stroke between patients who discontinued and those who continued taking beta-blockers, those who stopped taking the drugs had a higher rate of cardiovascular hospitalization.

Discontinuation was also associated with an increase in blood pressure and heart rate, without any improvement in quality of life.

“We thought we would be able to withdraw beta-blockers safely and that this would result in improved quality of life, but our trial results suggest this is not the case,” said lead investigator Johanne Silvain, MD, PhD, from Pitié-Salpêtrière University Hospital in Paris, who presented the ABYSS findings here at the European Society of Cardiology (ESC) Congress. 

The results, which were simultaneously published online in The New England Journal of Medicine, call into question current guidelines, which suggest that beta-blockers may be discontinued after 1 year in certain patient groups.

Beta-blockers have long been considered the standard of care for patients after MI, but trials showing the benefit of these drugs were conducted before the modern era of myocardial reperfusion and pharmacotherapy, which have led to sharp decreases in the risk for heart failure and for death after MI, Dr. Silvain explained. 

This has led to questions about the add-on benefits of lifelong beta-blocker treatment for patients with MI and a preserved left ventricular ejection fraction and no other primary indication for beta-blocker therapy.
 

The ABYSS Trial

To explore this issue, the open-label, non-inferiority ABYSS trial randomly assigned 3698 patients with a history of MI to the discontinuation or continuation of beta-blocker treatment. All study participants had a left ventricular ejection fraction of at least 40%, were receiving long-term beta-blocker treatment, and had experienced no cardiovascular event in the previous 6 months. 

At a median follow-up of 3 years, the primary endpoint — a composite of death, MI, stroke, and hospitalization for cardiovascular reasons — occurred more often in the discontinuation group than in the continuation group (23.8% vs 21.1%; hazard ratio, 1.16; 95% CI, 1.01-1.33). This did not meet the criteria for non-inferiority of discontinuation, compared with continuation, of beta-blocker therapy (P for non-inferiority = .44).

The difference in event rates between the two groups was driven by cardiovascular hospitalizations, which occurred more often in the discontinuation group than in the continuation group (18.9% vs 16.6%).

Other key results showed that there was no difference in quality of life between the two groups.

However, 6 months after randomization, there were increases in blood pressure and heart rate in the discontinuation group. Systolic blood pressure increased by 3.7 mm Hg and diastolic blood pressure increased by 3.9 mm Hg. Resting heart rate increased by 9.8 beats per minute.

“We were not able to show the non-inferiority of stopping beta-blockers in terms of cardiovascular events, [but we] showed a safety signal with this strategy of an increase in blood pressure and heart rate, with no improvement in quality of life,” Dr. Sylvain said.

“While recent guidelines suggest it may be reasonable to stop beta-blockers in this population, after these results, I will not be stopping these drugs if they are being well tolerated,” he said.

Sylvain said he was surprised that there was not an improvement in quality of life in the group that discontinued beta-blockers. “We are always told that beta-blockers have many side effects, so we expected to see an improvement in quality of life in the patients who stopped these drugs.”

One possible reason for the lack of improvement in quality of life is that the trial participants had been taking beta-blockers for several years. “We may have, therefore, selected patients who tolerate these drugs quite well. Those who had tolerance issues had probably already stopped taking them,” he explained.

In addition, the patient population had relatively high quality-of-life scores at baseline. “They were well treated and the therapies they were taking were well tolerated, so maybe it is difficult to improve quality of life further,” he said.
 

The REDUCE-AMI Trial

The ABYSS results appear at first to differ from results from the recent REDUCE-AMI trial, which failed to show the superiority of beta-blocker therapy, compared with no beta-blocker therapy, in acute MI patients with preserved ejection fraction.

But the REDUCE-AMI primary endpoint was a composite of death from any cause or new myocardial infarction; it did not include cardiovascular hospitalization, which was the main driver of the difference in outcomes in the ABYSS study, Dr. Sylvain pointed out.

“We showed an increase in coronary cases of hospitalization with stopping beta-blockers, and you have to remember that beta-blockers were developed to reduce coronary disease,” he said.
 

‘Slightly Inconclusive’

Jane Armitage, MBBS, University of Oxford, England, the ABYSS discussant for the ESC HOTLINE session, pointed out some limitations of the study, which led her to report that the result was “slightly inconclusive.” 

The open-label design may have allowed some bias regarding the cardiovascular hospitalization endpoint, she said.

“The decision whether to admit a patient to [the] hospital is somewhat subjective and could be influenced by a physician’s knowledge of treatment allocation. That is why, ideally, we prefer blinded trials. I think there are questions there,” she explained.

She also questioned whether the non-inferiority margin could have been increased, given the higher-than-expected event rate.

More data on this issue will come from several trials that are currently ongoing, Dr. Armitage said.

The ABYSS and REDUCE-AMI trials together suggest that it is safe, with respect to serious cardiac events, to stop beta-blocker treatment in MI patients with preserved ejection fraction, writes Tomas Jernberg, MD, PhD, from the Karolinska Institute in Stockholm, Sweden, in an accompanying editorial.

However, “because of the anti-ischemic effects of beta-blockers, an interruption may increase the risk of recurrent angina and the need for rehospitalization,” he adds.

“It is prudent to wait for the results of additional ongoing trials of beta-blockers involving patients with MI and a preserved left ventricular ejection fraction before definitively updating guidelines,” Dr. Jernberg concludes.

The ABYSS trial was funded by the French Ministry of Health and the ACTION Study Group. Dr. Sylvain, Dr. Armitage, and Dr. Jernberg report no relevant financial relationships.

A version of this article appeared on Medscape.com.