User login
Cardiology News is an independent news source that provides cardiologists with timely and relevant news and commentary about clinical developments and the impact of health care policy on cardiology and the cardiologist's practice. Cardiology News Digital Network is the online destination and multimedia properties of Cardiology News, the independent news publication for cardiologists. Cardiology news is the leading source of news and commentary about clinical developments in cardiology as well as health care policy and regulations that affect the cardiologist's practice. Cardiology News Digital Network is owned by Frontline Medical Communications.
Noise in medicine
A 26-year-old woman who reports a history of acyclovir-resistant herpes complains of a recurring, stinging rash around her mouth. Topical tacrolimus made it worse, she said. On exam, she has somewhat grouped pustules on her cutaneous lip. I mentioned her to colleagues, saying: “I’ve a patient with acyclovir-resistant herpes who isn’t improving on high-dose Valtrex.” They proffered a few alternative diagnoses and treatment recommendations. I tried several to no avail.
(it is after all only one condition). Nobel Prize–winning economist Daniel Kahneman, PhD, with two other authors, has written a brilliant book about this cognitive unreliability called “Noise: A Flaw in Human Judgment” (New York: Hachette Book Group, 2021).
Both bias and noise create trouble for us. Although biases get more attention, noise is both more prevalent and insidious. In a 2016 article, Dr. Kahneman and coauthors use a bathroom scale as an analogy to explain the difference. “We would say that the scale is biased if its readings are generally either too high or too low. A scale that consistently underestimates true weight by exactly 4 pounds is seriously biased but free of noise. A scale that gives two different readings when you step on it twice is noisy.” In the case presented, “measurements” by me and my colleagues were returning different “readings.” There is one true diagnosis and best treatment, yet because of noise, we waste time and resources by not getting it right the first time.
There is also evidence of bias in this case. For example, there’s probably some confirmation bias: The patient said she has a history of antiviral-resistant herpes; therefore, her rash might appear to be herpes. Also there might be salience bias: it’s easy to see how prominent pustules might be herpes simplex virus. Noise is an issue in many misdiagnoses, but trickier to see. In most instances, we don’t have the opportunity to get multiple assessments of the same case. When examined though, interrater reliability in medicine is often found to be shockingly low, an indication of how much noise there is in our clinical judgments. This leads to waste, frustration – and can even be dangerous when we’re trying to diagnose cancers such as melanoma, lung, or breast cancer.
Dr. Kahneman and colleagues have excellent recommendations on how to reduce noise, such as tips for good decision hygiene (e.g., using differential diagnoses) and using algorithms (e.g., calculating Apgar or LACE scores). I also liked their strategy of aggregating expert opinions. Fascinatingly, averaging multiple independent assessments is mathematically guaranteed to reduce noise. (God, I love economists). This is true of measurements and opinions: If you use 100 judgments for a case, you reduce noise by 90% (the noise is divided by the square root of the number of judgments averaged). So 20 colleagues’ opinions would reduce noise by almost 80%. However, those 20 opinions must be independent to avoid spurious agreement. (Again, math for the win.)
I showed photos of my patient to a few other dermatologists. They independently returned the same result: perioral dermatitis. This was the correct diagnosis and reminded me why grand rounds and tumor boards are such a great help. Multiple, independent assessments are more likely to get it right than just one opinion because we are canceling out the noise. But remember, grand rounds has to be old-school style – no looking at your coresident answers before giving yours!
Our patient cleared after restarting her topical tacrolimus and a bit of doxycycline. Credit the wisdom of the crowd. Reassuringly though, Dr. Kahneman also shows that expertise does matter in minimizing error. So that fellowship you did was still a great idea.
Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. He reports having no conflicts of interest. Write to him at [email protected].
A 26-year-old woman who reports a history of acyclovir-resistant herpes complains of a recurring, stinging rash around her mouth. Topical tacrolimus made it worse, she said. On exam, she has somewhat grouped pustules on her cutaneous lip. I mentioned her to colleagues, saying: “I’ve a patient with acyclovir-resistant herpes who isn’t improving on high-dose Valtrex.” They proffered a few alternative diagnoses and treatment recommendations. I tried several to no avail.
(it is after all only one condition). Nobel Prize–winning economist Daniel Kahneman, PhD, with two other authors, has written a brilliant book about this cognitive unreliability called “Noise: A Flaw in Human Judgment” (New York: Hachette Book Group, 2021).
Both bias and noise create trouble for us. Although biases get more attention, noise is both more prevalent and insidious. In a 2016 article, Dr. Kahneman and coauthors use a bathroom scale as an analogy to explain the difference. “We would say that the scale is biased if its readings are generally either too high or too low. A scale that consistently underestimates true weight by exactly 4 pounds is seriously biased but free of noise. A scale that gives two different readings when you step on it twice is noisy.” In the case presented, “measurements” by me and my colleagues were returning different “readings.” There is one true diagnosis and best treatment, yet because of noise, we waste time and resources by not getting it right the first time.
There is also evidence of bias in this case. For example, there’s probably some confirmation bias: The patient said she has a history of antiviral-resistant herpes; therefore, her rash might appear to be herpes. Also there might be salience bias: it’s easy to see how prominent pustules might be herpes simplex virus. Noise is an issue in many misdiagnoses, but trickier to see. In most instances, we don’t have the opportunity to get multiple assessments of the same case. When examined though, interrater reliability in medicine is often found to be shockingly low, an indication of how much noise there is in our clinical judgments. This leads to waste, frustration – and can even be dangerous when we’re trying to diagnose cancers such as melanoma, lung, or breast cancer.
Dr. Kahneman and colleagues have excellent recommendations on how to reduce noise, such as tips for good decision hygiene (e.g., using differential diagnoses) and using algorithms (e.g., calculating Apgar or LACE scores). I also liked their strategy of aggregating expert opinions. Fascinatingly, averaging multiple independent assessments is mathematically guaranteed to reduce noise. (God, I love economists). This is true of measurements and opinions: If you use 100 judgments for a case, you reduce noise by 90% (the noise is divided by the square root of the number of judgments averaged). So 20 colleagues’ opinions would reduce noise by almost 80%. However, those 20 opinions must be independent to avoid spurious agreement. (Again, math for the win.)
I showed photos of my patient to a few other dermatologists. They independently returned the same result: perioral dermatitis. This was the correct diagnosis and reminded me why grand rounds and tumor boards are such a great help. Multiple, independent assessments are more likely to get it right than just one opinion because we are canceling out the noise. But remember, grand rounds has to be old-school style – no looking at your coresident answers before giving yours!
Our patient cleared after restarting her topical tacrolimus and a bit of doxycycline. Credit the wisdom of the crowd. Reassuringly though, Dr. Kahneman also shows that expertise does matter in minimizing error. So that fellowship you did was still a great idea.
Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. He reports having no conflicts of interest. Write to him at [email protected].
A 26-year-old woman who reports a history of acyclovir-resistant herpes complains of a recurring, stinging rash around her mouth. Topical tacrolimus made it worse, she said. On exam, she has somewhat grouped pustules on her cutaneous lip. I mentioned her to colleagues, saying: “I’ve a patient with acyclovir-resistant herpes who isn’t improving on high-dose Valtrex.” They proffered a few alternative diagnoses and treatment recommendations. I tried several to no avail.
(it is after all only one condition). Nobel Prize–winning economist Daniel Kahneman, PhD, with two other authors, has written a brilliant book about this cognitive unreliability called “Noise: A Flaw in Human Judgment” (New York: Hachette Book Group, 2021).
Both bias and noise create trouble for us. Although biases get more attention, noise is both more prevalent and insidious. In a 2016 article, Dr. Kahneman and coauthors use a bathroom scale as an analogy to explain the difference. “We would say that the scale is biased if its readings are generally either too high or too low. A scale that consistently underestimates true weight by exactly 4 pounds is seriously biased but free of noise. A scale that gives two different readings when you step on it twice is noisy.” In the case presented, “measurements” by me and my colleagues were returning different “readings.” There is one true diagnosis and best treatment, yet because of noise, we waste time and resources by not getting it right the first time.
There is also evidence of bias in this case. For example, there’s probably some confirmation bias: The patient said she has a history of antiviral-resistant herpes; therefore, her rash might appear to be herpes. Also there might be salience bias: it’s easy to see how prominent pustules might be herpes simplex virus. Noise is an issue in many misdiagnoses, but trickier to see. In most instances, we don’t have the opportunity to get multiple assessments of the same case. When examined though, interrater reliability in medicine is often found to be shockingly low, an indication of how much noise there is in our clinical judgments. This leads to waste, frustration – and can even be dangerous when we’re trying to diagnose cancers such as melanoma, lung, or breast cancer.
Dr. Kahneman and colleagues have excellent recommendations on how to reduce noise, such as tips for good decision hygiene (e.g., using differential diagnoses) and using algorithms (e.g., calculating Apgar or LACE scores). I also liked their strategy of aggregating expert opinions. Fascinatingly, averaging multiple independent assessments is mathematically guaranteed to reduce noise. (God, I love economists). This is true of measurements and opinions: If you use 100 judgments for a case, you reduce noise by 90% (the noise is divided by the square root of the number of judgments averaged). So 20 colleagues’ opinions would reduce noise by almost 80%. However, those 20 opinions must be independent to avoid spurious agreement. (Again, math for the win.)
I showed photos of my patient to a few other dermatologists. They independently returned the same result: perioral dermatitis. This was the correct diagnosis and reminded me why grand rounds and tumor boards are such a great help. Multiple, independent assessments are more likely to get it right than just one opinion because we are canceling out the noise. But remember, grand rounds has to be old-school style – no looking at your coresident answers before giving yours!
Our patient cleared after restarting her topical tacrolimus and a bit of doxycycline. Credit the wisdom of the crowd. Reassuringly though, Dr. Kahneman also shows that expertise does matter in minimizing error. So that fellowship you did was still a great idea.
Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. He reports having no conflicts of interest. Write to him at [email protected].
New AHA guidance targets obesity-related hypertension
Whereas previous scientific statements from the American Heart Association have addressed how diet, physical activity, and weight control can help prevent and manage hypertension, a new AHA statement focuses on obesity-related hypertension.
The document, which was published online Sept. 20, 2021, in Hypertension, also identifies knowledge gaps and suggests future research directions.
“Given [that] obesity is a major risk factor for hypertension, and hypertension is one of the greatest (if not the greatest) attributable risk factors for most cardiovascular diseases, we thought it was important to focus on weight loss strategies and update what we know about the treatment options that are available to treat obesity hypertension,” writing group chair Michael E. Hall, MD, told this news organization.
“Medical and surgical strategies may help with long-term weight and blood pressure improvement, in addition to a heart-healthy diet and physical activity,” he noted in a press release from the AHA. “We often don’t consider medications or metabolic surgery until after there has been target organ damage, such as heart injury or having a stroke.”
However, by acting earlier, “we may be able to prevent these complications,” added Dr. Hall, associate division director for cardiovascular diseases at the University of Mississippi Medical Center in Jackson.
“This is not a call for greater use of one specific therapy,” he clarified. “However, we do know that more aggressive treatments including antiobesity medications or metabolic surgery are underutilized.”
According to Dr. Hall, “we treat the secondary problem [i.e., the hypertension or diabetes], but we are not treating the root cause [obesity] as aggressively.”
“Hopefully this statement will increase awareness that there are several [treatment] options [and] bring attention to this major health issue,” he said.
He added that the most important question, in his mind, is how best to tackle obesity among children and adolescents to lower their risk of hypertension and other associated complications.
The statement is aimed at both primary care providers and specialists.
Diet, physical activity help, but weight regain common
Losing 5%-10% of body weight can lead to a more than 5–mm Hg reduction in systolic blood pressure and a 4–mm Hg reduction in diastolic blood pressure, the statement notes. Losing 10 kg may lower systolic blood pressure by 5-20 mm Hg.
To manage weight, control hypertension, and reduce the risk of cardiovascular disease, guidelines recommend the Mediterranean diet or the Dietary Approaches to Stop Hypertension (DASH) diet, which both emphasize fruits, vegetables, legumes, nuts, and seeds, with moderate intake of fish, seafood, poultry, and dairy, and low intake of red and processed meats and sweets. The Mediterranean diet also includes olive oil and moderate consumption of (mainly red) wine.
The effect of intermittent fasting on blood pressure control is not clear, the statement noted.
It added that typically 150-225 minutes and 225-420 minutes of physical activity per week can produce weight loss of 2-3 kg or 5-7.5 kg respectively, and 200-300 minutes of physical activity per week is needed to maintain this weight loss.
“Successful weight-loss maintenance over years therefore typically requires high levels of [physical activity] and limited sedentary time, frequent weight monitoring, and high levels of dietary restraint,” and weight regain is common, the authors summarize.
Other options to address obesity, hypertension
Weight-loss pharmacotherapies and metabolic surgery are other options to treat obesity and lower hypertension.
The statement reports that four drugs are approved by the Food and Drug Administration for long-term weight loss: Orlistat (Xenical, Alli), phentermine/topiramate extended release (Qsymia), naltrexone/bupropion (Contrave), and liraglutide 3.0 mg (Saxenda). On June 4, the FDA approved a fifth drug, semaglutide (Wegovy).
The long-term effects of antiobesity medications on blood pressure are mixed.
However, “prescription rates for these drugs remain low, likely because of limited insurance coverage and low levels of clinical proficiency with treating obesity,” Dr. Hall and colleagues write.
Metabolic surgery could be a weight loss option for certain patients, and it is associated with blood pressure lowering.
In the 100-patient Gastric Bypass to Treat Obese Patients With Steady Hypertension (GATEWAY) trial, published in Circulation in 2018, more patients in the Roux-en-Y gastric-bypass group than the control group (84% vs. 13%) met the primary outcome of a 30% or greater reduction in the number of blood pressure-lowering medications at 12 months while maintaining an office blood pressure less than 140/90 mm Hg.
Unanswered questions, future research directions
In 2015-2016, an estimated 18.5% of U.S. children and adolescents aged 2-19 years had obesity, the statement notes. Children with obesity have a twofold increased risk of incident hypertension, and those with severe obesity have an over fourfold increased risk of this outcome, compared with children who have a healthy weight.
Dr. Hall and colleagues emphasized that, “as the prevalence of obesity continues to increase, hypertension and associated cardiorenal diseases will also increase unless more effective strategies to prevent and treat obesity are developed.”
They identified 17 unanswered questions (knowledge gaps) that can guide the direction of future research. These include:
- What new strategies and science-based guidelines are needed to curb the growing evidence of childhood obesity?
- Does intentional weight loss with pharmacotherapy or metabolic surgery in childhood and early adulthood prevent hypertension and subsequent target organ damage in later life?
- What is the optimal amount of time that clinicians should allow before recommending more aggressive weight management strategies (that is, antiobesity medications or metabolic surgery) or hypertension strategies beyond lifestyle changes?
“To me,” Dr. Hall said, “addressing childhood obesity hypertension and determining optimal timing of antiobesity therapies are the most important [issues]. Certainly, these therapies (i.e., diets, medications, surgeries) have some risks, but we don’t have a clear understanding if their benefits outweigh these risks in younger obese people or whether initiating these therapies before the onset of target organ damage such as heart failure” outweigh the risks.
Dr. Hall has reported no relevant financial relationships. Disclosures for the other authors are listed with the article.
A version of this article first appeared on Medscape.com.
Whereas previous scientific statements from the American Heart Association have addressed how diet, physical activity, and weight control can help prevent and manage hypertension, a new AHA statement focuses on obesity-related hypertension.
The document, which was published online Sept. 20, 2021, in Hypertension, also identifies knowledge gaps and suggests future research directions.
“Given [that] obesity is a major risk factor for hypertension, and hypertension is one of the greatest (if not the greatest) attributable risk factors for most cardiovascular diseases, we thought it was important to focus on weight loss strategies and update what we know about the treatment options that are available to treat obesity hypertension,” writing group chair Michael E. Hall, MD, told this news organization.
“Medical and surgical strategies may help with long-term weight and blood pressure improvement, in addition to a heart-healthy diet and physical activity,” he noted in a press release from the AHA. “We often don’t consider medications or metabolic surgery until after there has been target organ damage, such as heart injury or having a stroke.”
However, by acting earlier, “we may be able to prevent these complications,” added Dr. Hall, associate division director for cardiovascular diseases at the University of Mississippi Medical Center in Jackson.
“This is not a call for greater use of one specific therapy,” he clarified. “However, we do know that more aggressive treatments including antiobesity medications or metabolic surgery are underutilized.”
According to Dr. Hall, “we treat the secondary problem [i.e., the hypertension or diabetes], but we are not treating the root cause [obesity] as aggressively.”
“Hopefully this statement will increase awareness that there are several [treatment] options [and] bring attention to this major health issue,” he said.
He added that the most important question, in his mind, is how best to tackle obesity among children and adolescents to lower their risk of hypertension and other associated complications.
The statement is aimed at both primary care providers and specialists.
Diet, physical activity help, but weight regain common
Losing 5%-10% of body weight can lead to a more than 5–mm Hg reduction in systolic blood pressure and a 4–mm Hg reduction in diastolic blood pressure, the statement notes. Losing 10 kg may lower systolic blood pressure by 5-20 mm Hg.
To manage weight, control hypertension, and reduce the risk of cardiovascular disease, guidelines recommend the Mediterranean diet or the Dietary Approaches to Stop Hypertension (DASH) diet, which both emphasize fruits, vegetables, legumes, nuts, and seeds, with moderate intake of fish, seafood, poultry, and dairy, and low intake of red and processed meats and sweets. The Mediterranean diet also includes olive oil and moderate consumption of (mainly red) wine.
The effect of intermittent fasting on blood pressure control is not clear, the statement noted.
It added that typically 150-225 minutes and 225-420 minutes of physical activity per week can produce weight loss of 2-3 kg or 5-7.5 kg respectively, and 200-300 minutes of physical activity per week is needed to maintain this weight loss.
“Successful weight-loss maintenance over years therefore typically requires high levels of [physical activity] and limited sedentary time, frequent weight monitoring, and high levels of dietary restraint,” and weight regain is common, the authors summarize.
Other options to address obesity, hypertension
Weight-loss pharmacotherapies and metabolic surgery are other options to treat obesity and lower hypertension.
The statement reports that four drugs are approved by the Food and Drug Administration for long-term weight loss: Orlistat (Xenical, Alli), phentermine/topiramate extended release (Qsymia), naltrexone/bupropion (Contrave), and liraglutide 3.0 mg (Saxenda). On June 4, the FDA approved a fifth drug, semaglutide (Wegovy).
The long-term effects of antiobesity medications on blood pressure are mixed.
However, “prescription rates for these drugs remain low, likely because of limited insurance coverage and low levels of clinical proficiency with treating obesity,” Dr. Hall and colleagues write.
Metabolic surgery could be a weight loss option for certain patients, and it is associated with blood pressure lowering.
In the 100-patient Gastric Bypass to Treat Obese Patients With Steady Hypertension (GATEWAY) trial, published in Circulation in 2018, more patients in the Roux-en-Y gastric-bypass group than the control group (84% vs. 13%) met the primary outcome of a 30% or greater reduction in the number of blood pressure-lowering medications at 12 months while maintaining an office blood pressure less than 140/90 mm Hg.
Unanswered questions, future research directions
In 2015-2016, an estimated 18.5% of U.S. children and adolescents aged 2-19 years had obesity, the statement notes. Children with obesity have a twofold increased risk of incident hypertension, and those with severe obesity have an over fourfold increased risk of this outcome, compared with children who have a healthy weight.
Dr. Hall and colleagues emphasized that, “as the prevalence of obesity continues to increase, hypertension and associated cardiorenal diseases will also increase unless more effective strategies to prevent and treat obesity are developed.”
They identified 17 unanswered questions (knowledge gaps) that can guide the direction of future research. These include:
- What new strategies and science-based guidelines are needed to curb the growing evidence of childhood obesity?
- Does intentional weight loss with pharmacotherapy or metabolic surgery in childhood and early adulthood prevent hypertension and subsequent target organ damage in later life?
- What is the optimal amount of time that clinicians should allow before recommending more aggressive weight management strategies (that is, antiobesity medications or metabolic surgery) or hypertension strategies beyond lifestyle changes?
“To me,” Dr. Hall said, “addressing childhood obesity hypertension and determining optimal timing of antiobesity therapies are the most important [issues]. Certainly, these therapies (i.e., diets, medications, surgeries) have some risks, but we don’t have a clear understanding if their benefits outweigh these risks in younger obese people or whether initiating these therapies before the onset of target organ damage such as heart failure” outweigh the risks.
Dr. Hall has reported no relevant financial relationships. Disclosures for the other authors are listed with the article.
A version of this article first appeared on Medscape.com.
Whereas previous scientific statements from the American Heart Association have addressed how diet, physical activity, and weight control can help prevent and manage hypertension, a new AHA statement focuses on obesity-related hypertension.
The document, which was published online Sept. 20, 2021, in Hypertension, also identifies knowledge gaps and suggests future research directions.
“Given [that] obesity is a major risk factor for hypertension, and hypertension is one of the greatest (if not the greatest) attributable risk factors for most cardiovascular diseases, we thought it was important to focus on weight loss strategies and update what we know about the treatment options that are available to treat obesity hypertension,” writing group chair Michael E. Hall, MD, told this news organization.
“Medical and surgical strategies may help with long-term weight and blood pressure improvement, in addition to a heart-healthy diet and physical activity,” he noted in a press release from the AHA. “We often don’t consider medications or metabolic surgery until after there has been target organ damage, such as heart injury or having a stroke.”
However, by acting earlier, “we may be able to prevent these complications,” added Dr. Hall, associate division director for cardiovascular diseases at the University of Mississippi Medical Center in Jackson.
“This is not a call for greater use of one specific therapy,” he clarified. “However, we do know that more aggressive treatments including antiobesity medications or metabolic surgery are underutilized.”
According to Dr. Hall, “we treat the secondary problem [i.e., the hypertension or diabetes], but we are not treating the root cause [obesity] as aggressively.”
“Hopefully this statement will increase awareness that there are several [treatment] options [and] bring attention to this major health issue,” he said.
He added that the most important question, in his mind, is how best to tackle obesity among children and adolescents to lower their risk of hypertension and other associated complications.
The statement is aimed at both primary care providers and specialists.
Diet, physical activity help, but weight regain common
Losing 5%-10% of body weight can lead to a more than 5–mm Hg reduction in systolic blood pressure and a 4–mm Hg reduction in diastolic blood pressure, the statement notes. Losing 10 kg may lower systolic blood pressure by 5-20 mm Hg.
To manage weight, control hypertension, and reduce the risk of cardiovascular disease, guidelines recommend the Mediterranean diet or the Dietary Approaches to Stop Hypertension (DASH) diet, which both emphasize fruits, vegetables, legumes, nuts, and seeds, with moderate intake of fish, seafood, poultry, and dairy, and low intake of red and processed meats and sweets. The Mediterranean diet also includes olive oil and moderate consumption of (mainly red) wine.
The effect of intermittent fasting on blood pressure control is not clear, the statement noted.
It added that typically 150-225 minutes and 225-420 minutes of physical activity per week can produce weight loss of 2-3 kg or 5-7.5 kg respectively, and 200-300 minutes of physical activity per week is needed to maintain this weight loss.
“Successful weight-loss maintenance over years therefore typically requires high levels of [physical activity] and limited sedentary time, frequent weight monitoring, and high levels of dietary restraint,” and weight regain is common, the authors summarize.
Other options to address obesity, hypertension
Weight-loss pharmacotherapies and metabolic surgery are other options to treat obesity and lower hypertension.
The statement reports that four drugs are approved by the Food and Drug Administration for long-term weight loss: Orlistat (Xenical, Alli), phentermine/topiramate extended release (Qsymia), naltrexone/bupropion (Contrave), and liraglutide 3.0 mg (Saxenda). On June 4, the FDA approved a fifth drug, semaglutide (Wegovy).
The long-term effects of antiobesity medications on blood pressure are mixed.
However, “prescription rates for these drugs remain low, likely because of limited insurance coverage and low levels of clinical proficiency with treating obesity,” Dr. Hall and colleagues write.
Metabolic surgery could be a weight loss option for certain patients, and it is associated with blood pressure lowering.
In the 100-patient Gastric Bypass to Treat Obese Patients With Steady Hypertension (GATEWAY) trial, published in Circulation in 2018, more patients in the Roux-en-Y gastric-bypass group than the control group (84% vs. 13%) met the primary outcome of a 30% or greater reduction in the number of blood pressure-lowering medications at 12 months while maintaining an office blood pressure less than 140/90 mm Hg.
Unanswered questions, future research directions
In 2015-2016, an estimated 18.5% of U.S. children and adolescents aged 2-19 years had obesity, the statement notes. Children with obesity have a twofold increased risk of incident hypertension, and those with severe obesity have an over fourfold increased risk of this outcome, compared with children who have a healthy weight.
Dr. Hall and colleagues emphasized that, “as the prevalence of obesity continues to increase, hypertension and associated cardiorenal diseases will also increase unless more effective strategies to prevent and treat obesity are developed.”
They identified 17 unanswered questions (knowledge gaps) that can guide the direction of future research. These include:
- What new strategies and science-based guidelines are needed to curb the growing evidence of childhood obesity?
- Does intentional weight loss with pharmacotherapy or metabolic surgery in childhood and early adulthood prevent hypertension and subsequent target organ damage in later life?
- What is the optimal amount of time that clinicians should allow before recommending more aggressive weight management strategies (that is, antiobesity medications or metabolic surgery) or hypertension strategies beyond lifestyle changes?
“To me,” Dr. Hall said, “addressing childhood obesity hypertension and determining optimal timing of antiobesity therapies are the most important [issues]. Certainly, these therapies (i.e., diets, medications, surgeries) have some risks, but we don’t have a clear understanding if their benefits outweigh these risks in younger obese people or whether initiating these therapies before the onset of target organ damage such as heart failure” outweigh the risks.
Dr. Hall has reported no relevant financial relationships. Disclosures for the other authors are listed with the article.
A version of this article first appeared on Medscape.com.
FDA approves Abbott’s Portico valve for TAVR
The Food and Drug Administration has approved the Portico with FlexNav (Abbott) transcatheter aortic valve replacement (TAVR) system for patients with “symptomatic, severe aortic stenosis who are at high or extreme risk for open-heart surgery,” the company has announced.
The approval indication is in line with the entry criteria of PORTICO IDE, the investigational device exemption trial from which the FDA largely made its decision.
With the self-expanding Portico valve, Abbott joins two other companies with TAVR valves on the U.S. market: Medtronic with the self-expanding Corevalve Evolut (Medtronic) line, and Edwards Lifesciences with its Sapien (Edwards Lifesciences) valves, both of which can be used in patients at low surgical risk.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration has approved the Portico with FlexNav (Abbott) transcatheter aortic valve replacement (TAVR) system for patients with “symptomatic, severe aortic stenosis who are at high or extreme risk for open-heart surgery,” the company has announced.
The approval indication is in line with the entry criteria of PORTICO IDE, the investigational device exemption trial from which the FDA largely made its decision.
With the self-expanding Portico valve, Abbott joins two other companies with TAVR valves on the U.S. market: Medtronic with the self-expanding Corevalve Evolut (Medtronic) line, and Edwards Lifesciences with its Sapien (Edwards Lifesciences) valves, both of which can be used in patients at low surgical risk.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration has approved the Portico with FlexNav (Abbott) transcatheter aortic valve replacement (TAVR) system for patients with “symptomatic, severe aortic stenosis who are at high or extreme risk for open-heart surgery,” the company has announced.
The approval indication is in line with the entry criteria of PORTICO IDE, the investigational device exemption trial from which the FDA largely made its decision.
With the self-expanding Portico valve, Abbott joins two other companies with TAVR valves on the U.S. market: Medtronic with the self-expanding Corevalve Evolut (Medtronic) line, and Edwards Lifesciences with its Sapien (Edwards Lifesciences) valves, both of which can be used in patients at low surgical risk.
A version of this article first appeared on Medscape.com.
Refined heart rate cutoffs may improve prognostic value of acute PE scoring systems
In patients with acute pulmonary embolism, using cutoff values other than 110 beats per minute might improve the prognostic value of heart rate at admission, a recent observational study suggests.
For identifying low-risk patients, a cutoff of 80 bpm increased the sensitivity of the simplified Pulmonary Embolism Severity Index (sPESI) from about 94% to nearly 99% among nonhypotensive patients with acute symptomatic pulmonary embolism (PE), according to results of the large, registry-based study.
Similarly, using a 140-bpm cutoff increased the specificity of the Bova score for identifying intermediate-high–risk patients from about 93% to 98% in the study, which was recently published in the journal CHEST.
“Although standard dichotomization of HR [i.e., HR less than 110 vs. greater than 110 bpm] may be useful for guideline recommendations, our results will allow for more accuracy regarding clinical decision-making,” wrote lead author Ana Jaureguízar, MD, of the University of Alcalá in Madrid, on behalf of the RIETE (Registro Informatizado de la Enfermedad TromboEmbólica) investigators.
Intuitive findings inform future research
These observational findings are intuitive and do at least have the potential to inform the design of future randomized clinical trials, according to Albert J. Polito, MD, chief of the division of pulmonary medicine and medical director for the lung center at Mercy Medical Center in Baltimore.
“In medicine, there is a spectrum of risk,” Dr. Polito said in an interview. “While we love our cutoffs, which in this case has traditionally always been that 110 beats per minute for heart rate, it makes sense that there would be some range of risks of bad outcomes.”
Building on the observations of the present study, subsequent prospective randomized studies could potentially aim to determine, for example, when thrombolytic therapy should be considered in nonhypotensive patients with acute PE and higher heart rates.
“It would not be easy to design, but it’s a straightforward question to ask whether patients with the highest heart rates are the ones who potentially might benefit the most from thrombolytic therapy,” Dr. Polito said.
Value of alternative HR cutoffs
Heart rate is a simple and easily available vital sign that is clearly linked to prognosis in patients with pulmonary embolism, authors of the RIETE registry study say in their report. Accordingly, a heart rate threshold of 110 bpm has made its way into scoring systems that seek to identify low-risk patients, such as the sPESI, and those focused on identifying higher-risk patients, such as the Bova score.
However, it has not been clear whether alternative HR cutoffs would improve upon the 110-bpm threshold, they added. At the low-risk end, more accurate scoring systems could optimize the selection of patients for home treatment, while at the intermediate-high–risk end, they could better select patients for close monitoring or advanced PE treatments.
Better granularity on heart rate risks?
To better define the prognostic value of different heart rate thresholds, investigators analyzed data from RIETE, a large, ongoing, multinational prospective registry including patients with objectively confirmed acute venous thromboembolism.
For 44,331 consecutive nonhypotensive symptomatic PEs, the overall rate of 30-day all-cause mortality was 5.1%, and the 30-day PE-related mortality was 1.9%, the authors report.
Significantly poorer outcomes were seen in patients with higher heart rates as compared to patients in the 80-99 bpm range, they also found. As compared to that reference range, odds ratios for 30-day all-cause death ranged from 1.5 for heart rates of 100-109, up to 2.4 for those with heart rates of 140 bpm or greater.
Likewise, patients with higher heart rates had a 1.7- to 2.4-fold greater risk of 30-day PE-related death as compared to the 80- to 99-bpm reference range, while patients with lower heart rates had lesser risk, the data published in CHEST show.
Toward refinement of prognostic scoring
Next, investigators sought to refine the prognostic scoring systems for low-risk PE (sPESI) and intermediate-high–risk PE (Bova).
For sPESI, they found that dropping the cutoff value from 110 to 100 bpm increased the sensitivity of the score from 93.4% to 95.3%. Going down even further to 80 bpm increased sensitivity to 98.8%, according to the report.
By going down from 110 to 80 bpm, the proportion of patients defined as low-risk dropped from 35% to 12%, according to the investigators.
For the Bova score, increasing the cutoff value from 110 to 120 bpm likewise increased specificity from 93.2% to 95%, while going up even further to 140 bpm increased specificity to 98.0%, the report shows.
In sensitivity analyses, the findings were not impacted by excluding younger patients, those who received reperfusion therapies, or those with atrial fibrillation, according to the study findings.
Potential implications for clinical practice
Taken together, these findings could serve as a resource to inform discussions regarding PE management that include whether home therapy or use of thrombolytic therapy is appropriate, investigators said in their report.
“For instance, among low-risk sPESI patients, those with borderline tachycardia [i.e., a heart rate between 100-109 bpm] might benefit from initial hospital observation for trending,” they wrote.
Dr. Jaureguízar reported no disclosures. One coinvestigator reported funding support from the Institute of Health Carlos III (ISCIII) and the European Development Regional Fund (ERDF). One coinvestigator reported consulting in litigation involving two models of inferior vena cava filters.
Dr. Polito reported no disclosures.
In patients with acute pulmonary embolism, using cutoff values other than 110 beats per minute might improve the prognostic value of heart rate at admission, a recent observational study suggests.
For identifying low-risk patients, a cutoff of 80 bpm increased the sensitivity of the simplified Pulmonary Embolism Severity Index (sPESI) from about 94% to nearly 99% among nonhypotensive patients with acute symptomatic pulmonary embolism (PE), according to results of the large, registry-based study.
Similarly, using a 140-bpm cutoff increased the specificity of the Bova score for identifying intermediate-high–risk patients from about 93% to 98% in the study, which was recently published in the journal CHEST.
“Although standard dichotomization of HR [i.e., HR less than 110 vs. greater than 110 bpm] may be useful for guideline recommendations, our results will allow for more accuracy regarding clinical decision-making,” wrote lead author Ana Jaureguízar, MD, of the University of Alcalá in Madrid, on behalf of the RIETE (Registro Informatizado de la Enfermedad TromboEmbólica) investigators.
Intuitive findings inform future research
These observational findings are intuitive and do at least have the potential to inform the design of future randomized clinical trials, according to Albert J. Polito, MD, chief of the division of pulmonary medicine and medical director for the lung center at Mercy Medical Center in Baltimore.
“In medicine, there is a spectrum of risk,” Dr. Polito said in an interview. “While we love our cutoffs, which in this case has traditionally always been that 110 beats per minute for heart rate, it makes sense that there would be some range of risks of bad outcomes.”
Building on the observations of the present study, subsequent prospective randomized studies could potentially aim to determine, for example, when thrombolytic therapy should be considered in nonhypotensive patients with acute PE and higher heart rates.
“It would not be easy to design, but it’s a straightforward question to ask whether patients with the highest heart rates are the ones who potentially might benefit the most from thrombolytic therapy,” Dr. Polito said.
Value of alternative HR cutoffs
Heart rate is a simple and easily available vital sign that is clearly linked to prognosis in patients with pulmonary embolism, authors of the RIETE registry study say in their report. Accordingly, a heart rate threshold of 110 bpm has made its way into scoring systems that seek to identify low-risk patients, such as the sPESI, and those focused on identifying higher-risk patients, such as the Bova score.
However, it has not been clear whether alternative HR cutoffs would improve upon the 110-bpm threshold, they added. At the low-risk end, more accurate scoring systems could optimize the selection of patients for home treatment, while at the intermediate-high–risk end, they could better select patients for close monitoring or advanced PE treatments.
Better granularity on heart rate risks?
To better define the prognostic value of different heart rate thresholds, investigators analyzed data from RIETE, a large, ongoing, multinational prospective registry including patients with objectively confirmed acute venous thromboembolism.
For 44,331 consecutive nonhypotensive symptomatic PEs, the overall rate of 30-day all-cause mortality was 5.1%, and the 30-day PE-related mortality was 1.9%, the authors report.
Significantly poorer outcomes were seen in patients with higher heart rates as compared to patients in the 80-99 bpm range, they also found. As compared to that reference range, odds ratios for 30-day all-cause death ranged from 1.5 for heart rates of 100-109, up to 2.4 for those with heart rates of 140 bpm or greater.
Likewise, patients with higher heart rates had a 1.7- to 2.4-fold greater risk of 30-day PE-related death as compared to the 80- to 99-bpm reference range, while patients with lower heart rates had lesser risk, the data published in CHEST show.
Toward refinement of prognostic scoring
Next, investigators sought to refine the prognostic scoring systems for low-risk PE (sPESI) and intermediate-high–risk PE (Bova).
For sPESI, they found that dropping the cutoff value from 110 to 100 bpm increased the sensitivity of the score from 93.4% to 95.3%. Going down even further to 80 bpm increased sensitivity to 98.8%, according to the report.
By going down from 110 to 80 bpm, the proportion of patients defined as low-risk dropped from 35% to 12%, according to the investigators.
For the Bova score, increasing the cutoff value from 110 to 120 bpm likewise increased specificity from 93.2% to 95%, while going up even further to 140 bpm increased specificity to 98.0%, the report shows.
In sensitivity analyses, the findings were not impacted by excluding younger patients, those who received reperfusion therapies, or those with atrial fibrillation, according to the study findings.
Potential implications for clinical practice
Taken together, these findings could serve as a resource to inform discussions regarding PE management that include whether home therapy or use of thrombolytic therapy is appropriate, investigators said in their report.
“For instance, among low-risk sPESI patients, those with borderline tachycardia [i.e., a heart rate between 100-109 bpm] might benefit from initial hospital observation for trending,” they wrote.
Dr. Jaureguízar reported no disclosures. One coinvestigator reported funding support from the Institute of Health Carlos III (ISCIII) and the European Development Regional Fund (ERDF). One coinvestigator reported consulting in litigation involving two models of inferior vena cava filters.
Dr. Polito reported no disclosures.
In patients with acute pulmonary embolism, using cutoff values other than 110 beats per minute might improve the prognostic value of heart rate at admission, a recent observational study suggests.
For identifying low-risk patients, a cutoff of 80 bpm increased the sensitivity of the simplified Pulmonary Embolism Severity Index (sPESI) from about 94% to nearly 99% among nonhypotensive patients with acute symptomatic pulmonary embolism (PE), according to results of the large, registry-based study.
Similarly, using a 140-bpm cutoff increased the specificity of the Bova score for identifying intermediate-high–risk patients from about 93% to 98% in the study, which was recently published in the journal CHEST.
“Although standard dichotomization of HR [i.e., HR less than 110 vs. greater than 110 bpm] may be useful for guideline recommendations, our results will allow for more accuracy regarding clinical decision-making,” wrote lead author Ana Jaureguízar, MD, of the University of Alcalá in Madrid, on behalf of the RIETE (Registro Informatizado de la Enfermedad TromboEmbólica) investigators.
Intuitive findings inform future research
These observational findings are intuitive and do at least have the potential to inform the design of future randomized clinical trials, according to Albert J. Polito, MD, chief of the division of pulmonary medicine and medical director for the lung center at Mercy Medical Center in Baltimore.
“In medicine, there is a spectrum of risk,” Dr. Polito said in an interview. “While we love our cutoffs, which in this case has traditionally always been that 110 beats per minute for heart rate, it makes sense that there would be some range of risks of bad outcomes.”
Building on the observations of the present study, subsequent prospective randomized studies could potentially aim to determine, for example, when thrombolytic therapy should be considered in nonhypotensive patients with acute PE and higher heart rates.
“It would not be easy to design, but it’s a straightforward question to ask whether patients with the highest heart rates are the ones who potentially might benefit the most from thrombolytic therapy,” Dr. Polito said.
Value of alternative HR cutoffs
Heart rate is a simple and easily available vital sign that is clearly linked to prognosis in patients with pulmonary embolism, authors of the RIETE registry study say in their report. Accordingly, a heart rate threshold of 110 bpm has made its way into scoring systems that seek to identify low-risk patients, such as the sPESI, and those focused on identifying higher-risk patients, such as the Bova score.
However, it has not been clear whether alternative HR cutoffs would improve upon the 110-bpm threshold, they added. At the low-risk end, more accurate scoring systems could optimize the selection of patients for home treatment, while at the intermediate-high–risk end, they could better select patients for close monitoring or advanced PE treatments.
Better granularity on heart rate risks?
To better define the prognostic value of different heart rate thresholds, investigators analyzed data from RIETE, a large, ongoing, multinational prospective registry including patients with objectively confirmed acute venous thromboembolism.
For 44,331 consecutive nonhypotensive symptomatic PEs, the overall rate of 30-day all-cause mortality was 5.1%, and the 30-day PE-related mortality was 1.9%, the authors report.
Significantly poorer outcomes were seen in patients with higher heart rates as compared to patients in the 80-99 bpm range, they also found. As compared to that reference range, odds ratios for 30-day all-cause death ranged from 1.5 for heart rates of 100-109, up to 2.4 for those with heart rates of 140 bpm or greater.
Likewise, patients with higher heart rates had a 1.7- to 2.4-fold greater risk of 30-day PE-related death as compared to the 80- to 99-bpm reference range, while patients with lower heart rates had lesser risk, the data published in CHEST show.
Toward refinement of prognostic scoring
Next, investigators sought to refine the prognostic scoring systems for low-risk PE (sPESI) and intermediate-high–risk PE (Bova).
For sPESI, they found that dropping the cutoff value from 110 to 100 bpm increased the sensitivity of the score from 93.4% to 95.3%. Going down even further to 80 bpm increased sensitivity to 98.8%, according to the report.
By going down from 110 to 80 bpm, the proportion of patients defined as low-risk dropped from 35% to 12%, according to the investigators.
For the Bova score, increasing the cutoff value from 110 to 120 bpm likewise increased specificity from 93.2% to 95%, while going up even further to 140 bpm increased specificity to 98.0%, the report shows.
In sensitivity analyses, the findings were not impacted by excluding younger patients, those who received reperfusion therapies, or those with atrial fibrillation, according to the study findings.
Potential implications for clinical practice
Taken together, these findings could serve as a resource to inform discussions regarding PE management that include whether home therapy or use of thrombolytic therapy is appropriate, investigators said in their report.
“For instance, among low-risk sPESI patients, those with borderline tachycardia [i.e., a heart rate between 100-109 bpm] might benefit from initial hospital observation for trending,” they wrote.
Dr. Jaureguízar reported no disclosures. One coinvestigator reported funding support from the Institute of Health Carlos III (ISCIII) and the European Development Regional Fund (ERDF). One coinvestigator reported consulting in litigation involving two models of inferior vena cava filters.
Dr. Polito reported no disclosures.
FROM CHEST
COVID-19 claims more than 675,000 U.S. lives, surpassing the 1918 flu
, according to data collected by Johns Hopkins University.
Although the raw numbers match, epidemiologists point out that 675,000 deaths in 1918 was a much greater proportion of the population. In 1918, the U.S. population was 105 million, less than one third of what it is today.
The AIDS pandemic of the 1980s remains the deadliest of the 20th Century, claiming the lives of 700,000 Americans. But at our current pace of 2,000 COVID deaths a day, we could quickly eclipse that death toll, too.
Even though the 1918 epidemic is often called the “Spanish Flu,” there is no universal consensus regarding where the virus originated, according to the Centers for Disease Control and Prevention.
Still, the almost incomprehensible loss harkens back to a time when medicine and technology were far less advanced than they are today.
In 1918, the United States didn’t have access to a vaccine, or near real-time tools to trace the spread and communicate the threat.
In some ways, the United States has failed to learn from the mistakes of the past.
There are many similarities between the two pandemics. In the spring of 1918, when the first wave of influenza hit, the United States and its allies were nearing victory in Europe in World War I. Just this summer the United States has ended its longest war, the conflict in Afghanistan, as COVID cases surge.
In both pandemics, hospitals and funeral homes were overrun and makeshift clinics were opened where space was available. Mask mandates were installed; schools, churches, and theaters closed; and social distancing was encouraged.
As is the case today, different jurisdictions took different steps to fight the pandemic and some were more successful than others.
According to History.com, in 1918, Philadelphia’s mayor said a popular annual parade could be held, and an estimated 200,000 people attended. In less than 2 weeks, more than 1,000 local residents were dead. But in St. Louis, public gatherings were banned, schools and theaters closed, and the death toll there was one eighth of Philadelphia’s.
Just as in 1918, America has at times continued to fan the flames of the epidemic by relaxing restrictions too quickly and relying on unproven treatments. Poor communication allowed younger people to feel that they wouldn’t necessarily face the worst consequences of the virus, contributing to a false sense of security in the age group that was fueling the spread.
“A lot of the mistakes that we definitely fell into in 1918, we hoped we wouldn’t fall into in 2020,” epidemiologist Stephen Kissler, PhD, of the Harvard T.H. Chan School of Public Health, told CNN. “We did.”
A version of this article first appeared on Medscape.com.
, according to data collected by Johns Hopkins University.
Although the raw numbers match, epidemiologists point out that 675,000 deaths in 1918 was a much greater proportion of the population. In 1918, the U.S. population was 105 million, less than one third of what it is today.
The AIDS pandemic of the 1980s remains the deadliest of the 20th Century, claiming the lives of 700,000 Americans. But at our current pace of 2,000 COVID deaths a day, we could quickly eclipse that death toll, too.
Even though the 1918 epidemic is often called the “Spanish Flu,” there is no universal consensus regarding where the virus originated, according to the Centers for Disease Control and Prevention.
Still, the almost incomprehensible loss harkens back to a time when medicine and technology were far less advanced than they are today.
In 1918, the United States didn’t have access to a vaccine, or near real-time tools to trace the spread and communicate the threat.
In some ways, the United States has failed to learn from the mistakes of the past.
There are many similarities between the two pandemics. In the spring of 1918, when the first wave of influenza hit, the United States and its allies were nearing victory in Europe in World War I. Just this summer the United States has ended its longest war, the conflict in Afghanistan, as COVID cases surge.
In both pandemics, hospitals and funeral homes were overrun and makeshift clinics were opened where space was available. Mask mandates were installed; schools, churches, and theaters closed; and social distancing was encouraged.
As is the case today, different jurisdictions took different steps to fight the pandemic and some were more successful than others.
According to History.com, in 1918, Philadelphia’s mayor said a popular annual parade could be held, and an estimated 200,000 people attended. In less than 2 weeks, more than 1,000 local residents were dead. But in St. Louis, public gatherings were banned, schools and theaters closed, and the death toll there was one eighth of Philadelphia’s.
Just as in 1918, America has at times continued to fan the flames of the epidemic by relaxing restrictions too quickly and relying on unproven treatments. Poor communication allowed younger people to feel that they wouldn’t necessarily face the worst consequences of the virus, contributing to a false sense of security in the age group that was fueling the spread.
“A lot of the mistakes that we definitely fell into in 1918, we hoped we wouldn’t fall into in 2020,” epidemiologist Stephen Kissler, PhD, of the Harvard T.H. Chan School of Public Health, told CNN. “We did.”
A version of this article first appeared on Medscape.com.
, according to data collected by Johns Hopkins University.
Although the raw numbers match, epidemiologists point out that 675,000 deaths in 1918 was a much greater proportion of the population. In 1918, the U.S. population was 105 million, less than one third of what it is today.
The AIDS pandemic of the 1980s remains the deadliest of the 20th Century, claiming the lives of 700,000 Americans. But at our current pace of 2,000 COVID deaths a day, we could quickly eclipse that death toll, too.
Even though the 1918 epidemic is often called the “Spanish Flu,” there is no universal consensus regarding where the virus originated, according to the Centers for Disease Control and Prevention.
Still, the almost incomprehensible loss harkens back to a time when medicine and technology were far less advanced than they are today.
In 1918, the United States didn’t have access to a vaccine, or near real-time tools to trace the spread and communicate the threat.
In some ways, the United States has failed to learn from the mistakes of the past.
There are many similarities between the two pandemics. In the spring of 1918, when the first wave of influenza hit, the United States and its allies were nearing victory in Europe in World War I. Just this summer the United States has ended its longest war, the conflict in Afghanistan, as COVID cases surge.
In both pandemics, hospitals and funeral homes were overrun and makeshift clinics were opened where space was available. Mask mandates were installed; schools, churches, and theaters closed; and social distancing was encouraged.
As is the case today, different jurisdictions took different steps to fight the pandemic and some were more successful than others.
According to History.com, in 1918, Philadelphia’s mayor said a popular annual parade could be held, and an estimated 200,000 people attended. In less than 2 weeks, more than 1,000 local residents were dead. But in St. Louis, public gatherings were banned, schools and theaters closed, and the death toll there was one eighth of Philadelphia’s.
Just as in 1918, America has at times continued to fan the flames of the epidemic by relaxing restrictions too quickly and relying on unproven treatments. Poor communication allowed younger people to feel that they wouldn’t necessarily face the worst consequences of the virus, contributing to a false sense of security in the age group that was fueling the spread.
“A lot of the mistakes that we definitely fell into in 1918, we hoped we wouldn’t fall into in 2020,” epidemiologist Stephen Kissler, PhD, of the Harvard T.H. Chan School of Public Health, told CNN. “We did.”
A version of this article first appeared on Medscape.com.
EMPEROR-Preserved: Empagliflozin’s HFpEF efficacy catalyzes a heart failure redefinition
Groundbreaking results from the EMPEROR-Preserved trial did more than establish for the first time that a drug, empagliflozin, has clearly proven efficacy for treating patients with heart failure with preserved ejection fraction (HFpEF). The results also helped catalyze a paradigm shift in how heart failure thought leaders think about the role of ejection fraction for making important distinctions among patients with heart failure.
EMPEROR-Preserved may also be the final nail in the coffin for defining patients with heart failure as having HFpEF or heart failure with reduced ejection fraction (HFrEF).
This new consensus essentially throws out left ventricular ejection fraction (EF) as the key metric for matching patients to heart failure treatments. Experts have instead begun suggesting a more unified treatment approach for all heart failure patients regardless of their EF.
‘Forget about ejection fraction’
“We encourage you to forget about ejection fraction,” declared Milton Packer, MD, during discussion at a session of the annual scientific meeting of the Heart Failure Society of America. “We certainly encourage you to forget about an ejection fraction of less than 40%” as having special significance,” added Dr. Packer, a lead investigator for both the EMPEROR-Reduced and EMPEROR-Preserved trials (which researchers combined in a unified analysis with a total of 9,718 patients with heart failure called EMPEROR-Pooled), and a heart failure researcher at Baylor University Medical Center in Dallas.
“The 40% ejection fraction divide is artificial. It was created in 2003 as part of a trial design, but it has no physiological significance,” Dr. Packer explained. A much better way to distinguish systolic and diastolic heart failure is by strain assessment rather than by ejection fraction. “Strain is a measure of myocardial shortening, a measure of what the heart does. Ejection fraction is a measure of volume,” said Dr. Packer. “Sign me up to get rid of ejection fraction,” he added.
“Ejection fraction is not as valuable as we thought for distinguishing the therapeutic benefit” of heart failure drugs, agreed Marvin A. Konstam, MD, professor of medicine at Tufts University and chief physician executive of the CardioVascular Center of Tufts Medical Center, both in Boston, who spoke during a different session at the meeting.
“It would easier if we didn’t spend time parsing this number,” ejection fraction, commented Clyde W. Yancy, MD, professor of medicine and chief of cardiology at Northwestern Medicine in Chicago. “Wouldn’t it be easier if we said that every patient with heart failure needs to receive one agent from each of the four [pillar] drug classes, and put them in a polypill” at reduced dosages, he proposed, envisioning one potential consequence of jettisoning ejection fraction.
The four pillar drug classes, recently identified as essential for patients with HFrEF but until now not endorsed for patients with HFpEF, are the sodium-glucose cotransporter 2 (SGLT2) inhibitors, such as empagliflozin (Jardiance); an angiotensin receptor blocker neprilysin inhibitor compound such as sacubitril/valsartan (Entresto); beta-blockers; and mineralocorticoid receptor antagonists such as spironolactone and eplerenone.
An opportunity for ‘simpler and easier’ treatments
“This is an opportunity to disrupt the way we’ve been doing things and think about something that is simpler and easier,” said Dr. Yancy, who chaired some of the panels serially formed by the American Heart Association and American College of Cardiology to write guidelines for treating heart failure. “An approach that would be easier to implement without worrying about staggering the start of each drug class and an incessant focus on titrating individual elements and taking 6 months to get to a certain place.”
Results from EMPEROR-Preserved and the combined EMPEROR-Pooled analysis triggered these paradigm-shifting sentiments by showing clear evidence that treatment with empagliflozin exerts consistent benefit – and is consistently safe – for patients with heart failure across a spectrum of EFs, from less than 25% to 64%, though its performance in patients with HFpEF and EFs of 65% or greater in the EMPEROR-Preserved trial remains unclear.
The consequence is that clinicians should feel comfortable prescribing empagliflozin to most patients with heart failure without regard to EF, even patients with EF values in the mid-60% range.
The EMPEROR-Preserved results showed a clear signal of attenuated benefit among patients with an EF of 65% or greater “on a population basis,” stressed Dr. Packer. “But on an individual basis, ejection fraction is not that reproducible, so measuring ejection fraction will not help you determine whom to treat or not treat. “
“There is significant variability” measuring EF using the most common modality, echocardiography, noted Javed Butler, MD, an EMPEROR coinvestigator who also spoke at the meeting session. A person with a measured EF of 65% could actually have a value that may be as low as 58% or as high as about 72%, noted Dr. Butler, who is professor and chair of medicine at the University of Mississippi, Jackson. The upshot is that any patient diagnosed with heart failure should receive an SGLT2 inhibitor “irrespective of their ejection fraction,” Dr. Butler advised.
“Ejection fraction is very crude, and probably not sufficient to identify a phenotype,” for treatment, said Dr. Yancy. “The real takeaway may be that we need to revisit what we call HFrEF, and then let that be the new standard for treatment.”
“Is [an EF of] 60% the new 40%?” asked Dr. Packer, implying that the answer was yes.
Results from several trials suggest redefining HFrEF
The idea that patients without traditionally defined HFrEF – an EF of 40% or less – could also benefit from other classes of heart failure drugs has been gestating for a while, and then rose to a new level with the August 2021 report of results from EMPEROR-Preserved. Two years ago, in September 2019, Dr. Butler, Dr. Packer, and a third colleague advanced the notion of redefining HFrEF by raising the ejection fraction ceiling in a published commentary.
They cited the experience with the angiotensin receptor blocker candesartan in a post hoc analysis of data collected in the CHARM-Preserved trial, which showed a strong signal of benefit in the subgroup of patients with EFs of 41%-49%, but not in those with an EF of 50% or higher. This finding prompted Dr. Konstam to express doubts about relying on EF to define heart failure subgroups in trials and guide management in a commentary published more than 3 years ago.
Another crack in the traditional EF framework came from analysis of results from the TOPCAT trial that tested spironolactone as a treatment for patients with HFpEF, according to the 2019 opinion published by Dr. Butler and Dr. Packer. Once again a post hoc analysis, this time using data from TOPCAT, suggested a benefit from the mineralocorticoid receptor antagonist spironolactone in patients with heart failure and an EF of 45%-49% (45% was the minimum EF for enrollment into the study).
Recently, data from a third trial that tested sacubitril/valsartan in patients with HFpEF, PARAGON-HF, showed benefit among patients with EFs below the study median of 57%. This finding led the Food and Drug Administration in February 2021 to amend its initial approval for sacubitril/valsartan by removing a specific EF ceiling from the drug’s indication and instead saying that patient’s receiving the drug should have a “below normal” EF.
Writing in a recent commentary, Dr. Yancy called the FDA’s action on sacubitril/valsartan “reasonable,” and that the subgroup assessment of data from the PARAGON-HF trial creates a “new, reasonably evidence-based therapy for HFpEF.” He also predicted that guideline-writing panels will “likely align with a permissive statement of indication” for sacubitril/valsartan in patients with HFpEF, especially those with EFs of less than 57%.
The idea of using an SGLT2 inhibitor like empagliflozin on all heart failure patients, and also adding agents like sacubitril/valsartan and spironolactone in patients with HFpEF and EFs in the mid-50% range or lower may take some time to catch on, but it already has one influential advocate.
“If a patient has HFpEF with an EF of less than 55%, use quadruple-class therapy,” summed up Dr. Butler during the HFSA session, while also suggesting prescribing an SGLT2 inhibitor to essentially all patients with heart failure regardless of their EF.
The EMPEROR-Preserved and EMPEROR-Reduced trials and the EMPEROR-Pooled analysis were sponsored by Boehringer Ingelheim and Lilly, the companies that jointly market empagliflozin (Jardiance). Dr. Packer has had financial relationships with BI and Lilly and numerous other companies. Dr. Konstam has served on data monitoring committees for trials funded by Boehringer Ingelheim and by Amgen, Luitpold, and Pfizer, and has been a consultant to Arena, LivaNova, Merck, SC Pharma, and Takeda. Dr. Yancy had no disclosures. Dr. Butler has had financial relationships with Boehringer Ingelheim and numerous other companies.
Groundbreaking results from the EMPEROR-Preserved trial did more than establish for the first time that a drug, empagliflozin, has clearly proven efficacy for treating patients with heart failure with preserved ejection fraction (HFpEF). The results also helped catalyze a paradigm shift in how heart failure thought leaders think about the role of ejection fraction for making important distinctions among patients with heart failure.
EMPEROR-Preserved may also be the final nail in the coffin for defining patients with heart failure as having HFpEF or heart failure with reduced ejection fraction (HFrEF).
This new consensus essentially throws out left ventricular ejection fraction (EF) as the key metric for matching patients to heart failure treatments. Experts have instead begun suggesting a more unified treatment approach for all heart failure patients regardless of their EF.
‘Forget about ejection fraction’
“We encourage you to forget about ejection fraction,” declared Milton Packer, MD, during discussion at a session of the annual scientific meeting of the Heart Failure Society of America. “We certainly encourage you to forget about an ejection fraction of less than 40%” as having special significance,” added Dr. Packer, a lead investigator for both the EMPEROR-Reduced and EMPEROR-Preserved trials (which researchers combined in a unified analysis with a total of 9,718 patients with heart failure called EMPEROR-Pooled), and a heart failure researcher at Baylor University Medical Center in Dallas.
“The 40% ejection fraction divide is artificial. It was created in 2003 as part of a trial design, but it has no physiological significance,” Dr. Packer explained. A much better way to distinguish systolic and diastolic heart failure is by strain assessment rather than by ejection fraction. “Strain is a measure of myocardial shortening, a measure of what the heart does. Ejection fraction is a measure of volume,” said Dr. Packer. “Sign me up to get rid of ejection fraction,” he added.
“Ejection fraction is not as valuable as we thought for distinguishing the therapeutic benefit” of heart failure drugs, agreed Marvin A. Konstam, MD, professor of medicine at Tufts University and chief physician executive of the CardioVascular Center of Tufts Medical Center, both in Boston, who spoke during a different session at the meeting.
“It would easier if we didn’t spend time parsing this number,” ejection fraction, commented Clyde W. Yancy, MD, professor of medicine and chief of cardiology at Northwestern Medicine in Chicago. “Wouldn’t it be easier if we said that every patient with heart failure needs to receive one agent from each of the four [pillar] drug classes, and put them in a polypill” at reduced dosages, he proposed, envisioning one potential consequence of jettisoning ejection fraction.
The four pillar drug classes, recently identified as essential for patients with HFrEF but until now not endorsed for patients with HFpEF, are the sodium-glucose cotransporter 2 (SGLT2) inhibitors, such as empagliflozin (Jardiance); an angiotensin receptor blocker neprilysin inhibitor compound such as sacubitril/valsartan (Entresto); beta-blockers; and mineralocorticoid receptor antagonists such as spironolactone and eplerenone.
An opportunity for ‘simpler and easier’ treatments
“This is an opportunity to disrupt the way we’ve been doing things and think about something that is simpler and easier,” said Dr. Yancy, who chaired some of the panels serially formed by the American Heart Association and American College of Cardiology to write guidelines for treating heart failure. “An approach that would be easier to implement without worrying about staggering the start of each drug class and an incessant focus on titrating individual elements and taking 6 months to get to a certain place.”
Results from EMPEROR-Preserved and the combined EMPEROR-Pooled analysis triggered these paradigm-shifting sentiments by showing clear evidence that treatment with empagliflozin exerts consistent benefit – and is consistently safe – for patients with heart failure across a spectrum of EFs, from less than 25% to 64%, though its performance in patients with HFpEF and EFs of 65% or greater in the EMPEROR-Preserved trial remains unclear.
The consequence is that clinicians should feel comfortable prescribing empagliflozin to most patients with heart failure without regard to EF, even patients with EF values in the mid-60% range.
The EMPEROR-Preserved results showed a clear signal of attenuated benefit among patients with an EF of 65% or greater “on a population basis,” stressed Dr. Packer. “But on an individual basis, ejection fraction is not that reproducible, so measuring ejection fraction will not help you determine whom to treat or not treat. “
“There is significant variability” measuring EF using the most common modality, echocardiography, noted Javed Butler, MD, an EMPEROR coinvestigator who also spoke at the meeting session. A person with a measured EF of 65% could actually have a value that may be as low as 58% or as high as about 72%, noted Dr. Butler, who is professor and chair of medicine at the University of Mississippi, Jackson. The upshot is that any patient diagnosed with heart failure should receive an SGLT2 inhibitor “irrespective of their ejection fraction,” Dr. Butler advised.
“Ejection fraction is very crude, and probably not sufficient to identify a phenotype,” for treatment, said Dr. Yancy. “The real takeaway may be that we need to revisit what we call HFrEF, and then let that be the new standard for treatment.”
“Is [an EF of] 60% the new 40%?” asked Dr. Packer, implying that the answer was yes.
Results from several trials suggest redefining HFrEF
The idea that patients without traditionally defined HFrEF – an EF of 40% or less – could also benefit from other classes of heart failure drugs has been gestating for a while, and then rose to a new level with the August 2021 report of results from EMPEROR-Preserved. Two years ago, in September 2019, Dr. Butler, Dr. Packer, and a third colleague advanced the notion of redefining HFrEF by raising the ejection fraction ceiling in a published commentary.
They cited the experience with the angiotensin receptor blocker candesartan in a post hoc analysis of data collected in the CHARM-Preserved trial, which showed a strong signal of benefit in the subgroup of patients with EFs of 41%-49%, but not in those with an EF of 50% or higher. This finding prompted Dr. Konstam to express doubts about relying on EF to define heart failure subgroups in trials and guide management in a commentary published more than 3 years ago.
Another crack in the traditional EF framework came from analysis of results from the TOPCAT trial that tested spironolactone as a treatment for patients with HFpEF, according to the 2019 opinion published by Dr. Butler and Dr. Packer. Once again a post hoc analysis, this time using data from TOPCAT, suggested a benefit from the mineralocorticoid receptor antagonist spironolactone in patients with heart failure and an EF of 45%-49% (45% was the minimum EF for enrollment into the study).
Recently, data from a third trial that tested sacubitril/valsartan in patients with HFpEF, PARAGON-HF, showed benefit among patients with EFs below the study median of 57%. This finding led the Food and Drug Administration in February 2021 to amend its initial approval for sacubitril/valsartan by removing a specific EF ceiling from the drug’s indication and instead saying that patient’s receiving the drug should have a “below normal” EF.
Writing in a recent commentary, Dr. Yancy called the FDA’s action on sacubitril/valsartan “reasonable,” and that the subgroup assessment of data from the PARAGON-HF trial creates a “new, reasonably evidence-based therapy for HFpEF.” He also predicted that guideline-writing panels will “likely align with a permissive statement of indication” for sacubitril/valsartan in patients with HFpEF, especially those with EFs of less than 57%.
The idea of using an SGLT2 inhibitor like empagliflozin on all heart failure patients, and also adding agents like sacubitril/valsartan and spironolactone in patients with HFpEF and EFs in the mid-50% range or lower may take some time to catch on, but it already has one influential advocate.
“If a patient has HFpEF with an EF of less than 55%, use quadruple-class therapy,” summed up Dr. Butler during the HFSA session, while also suggesting prescribing an SGLT2 inhibitor to essentially all patients with heart failure regardless of their EF.
The EMPEROR-Preserved and EMPEROR-Reduced trials and the EMPEROR-Pooled analysis were sponsored by Boehringer Ingelheim and Lilly, the companies that jointly market empagliflozin (Jardiance). Dr. Packer has had financial relationships with BI and Lilly and numerous other companies. Dr. Konstam has served on data monitoring committees for trials funded by Boehringer Ingelheim and by Amgen, Luitpold, and Pfizer, and has been a consultant to Arena, LivaNova, Merck, SC Pharma, and Takeda. Dr. Yancy had no disclosures. Dr. Butler has had financial relationships with Boehringer Ingelheim and numerous other companies.
Groundbreaking results from the EMPEROR-Preserved trial did more than establish for the first time that a drug, empagliflozin, has clearly proven efficacy for treating patients with heart failure with preserved ejection fraction (HFpEF). The results also helped catalyze a paradigm shift in how heart failure thought leaders think about the role of ejection fraction for making important distinctions among patients with heart failure.
EMPEROR-Preserved may also be the final nail in the coffin for defining patients with heart failure as having HFpEF or heart failure with reduced ejection fraction (HFrEF).
This new consensus essentially throws out left ventricular ejection fraction (EF) as the key metric for matching patients to heart failure treatments. Experts have instead begun suggesting a more unified treatment approach for all heart failure patients regardless of their EF.
‘Forget about ejection fraction’
“We encourage you to forget about ejection fraction,” declared Milton Packer, MD, during discussion at a session of the annual scientific meeting of the Heart Failure Society of America. “We certainly encourage you to forget about an ejection fraction of less than 40%” as having special significance,” added Dr. Packer, a lead investigator for both the EMPEROR-Reduced and EMPEROR-Preserved trials (which researchers combined in a unified analysis with a total of 9,718 patients with heart failure called EMPEROR-Pooled), and a heart failure researcher at Baylor University Medical Center in Dallas.
“The 40% ejection fraction divide is artificial. It was created in 2003 as part of a trial design, but it has no physiological significance,” Dr. Packer explained. A much better way to distinguish systolic and diastolic heart failure is by strain assessment rather than by ejection fraction. “Strain is a measure of myocardial shortening, a measure of what the heart does. Ejection fraction is a measure of volume,” said Dr. Packer. “Sign me up to get rid of ejection fraction,” he added.
“Ejection fraction is not as valuable as we thought for distinguishing the therapeutic benefit” of heart failure drugs, agreed Marvin A. Konstam, MD, professor of medicine at Tufts University and chief physician executive of the CardioVascular Center of Tufts Medical Center, both in Boston, who spoke during a different session at the meeting.
“It would easier if we didn’t spend time parsing this number,” ejection fraction, commented Clyde W. Yancy, MD, professor of medicine and chief of cardiology at Northwestern Medicine in Chicago. “Wouldn’t it be easier if we said that every patient with heart failure needs to receive one agent from each of the four [pillar] drug classes, and put them in a polypill” at reduced dosages, he proposed, envisioning one potential consequence of jettisoning ejection fraction.
The four pillar drug classes, recently identified as essential for patients with HFrEF but until now not endorsed for patients with HFpEF, are the sodium-glucose cotransporter 2 (SGLT2) inhibitors, such as empagliflozin (Jardiance); an angiotensin receptor blocker neprilysin inhibitor compound such as sacubitril/valsartan (Entresto); beta-blockers; and mineralocorticoid receptor antagonists such as spironolactone and eplerenone.
An opportunity for ‘simpler and easier’ treatments
“This is an opportunity to disrupt the way we’ve been doing things and think about something that is simpler and easier,” said Dr. Yancy, who chaired some of the panels serially formed by the American Heart Association and American College of Cardiology to write guidelines for treating heart failure. “An approach that would be easier to implement without worrying about staggering the start of each drug class and an incessant focus on titrating individual elements and taking 6 months to get to a certain place.”
Results from EMPEROR-Preserved and the combined EMPEROR-Pooled analysis triggered these paradigm-shifting sentiments by showing clear evidence that treatment with empagliflozin exerts consistent benefit – and is consistently safe – for patients with heart failure across a spectrum of EFs, from less than 25% to 64%, though its performance in patients with HFpEF and EFs of 65% or greater in the EMPEROR-Preserved trial remains unclear.
The consequence is that clinicians should feel comfortable prescribing empagliflozin to most patients with heart failure without regard to EF, even patients with EF values in the mid-60% range.
The EMPEROR-Preserved results showed a clear signal of attenuated benefit among patients with an EF of 65% or greater “on a population basis,” stressed Dr. Packer. “But on an individual basis, ejection fraction is not that reproducible, so measuring ejection fraction will not help you determine whom to treat or not treat. “
“There is significant variability” measuring EF using the most common modality, echocardiography, noted Javed Butler, MD, an EMPEROR coinvestigator who also spoke at the meeting session. A person with a measured EF of 65% could actually have a value that may be as low as 58% or as high as about 72%, noted Dr. Butler, who is professor and chair of medicine at the University of Mississippi, Jackson. The upshot is that any patient diagnosed with heart failure should receive an SGLT2 inhibitor “irrespective of their ejection fraction,” Dr. Butler advised.
“Ejection fraction is very crude, and probably not sufficient to identify a phenotype,” for treatment, said Dr. Yancy. “The real takeaway may be that we need to revisit what we call HFrEF, and then let that be the new standard for treatment.”
“Is [an EF of] 60% the new 40%?” asked Dr. Packer, implying that the answer was yes.
Results from several trials suggest redefining HFrEF
The idea that patients without traditionally defined HFrEF – an EF of 40% or less – could also benefit from other classes of heart failure drugs has been gestating for a while, and then rose to a new level with the August 2021 report of results from EMPEROR-Preserved. Two years ago, in September 2019, Dr. Butler, Dr. Packer, and a third colleague advanced the notion of redefining HFrEF by raising the ejection fraction ceiling in a published commentary.
They cited the experience with the angiotensin receptor blocker candesartan in a post hoc analysis of data collected in the CHARM-Preserved trial, which showed a strong signal of benefit in the subgroup of patients with EFs of 41%-49%, but not in those with an EF of 50% or higher. This finding prompted Dr. Konstam to express doubts about relying on EF to define heart failure subgroups in trials and guide management in a commentary published more than 3 years ago.
Another crack in the traditional EF framework came from analysis of results from the TOPCAT trial that tested spironolactone as a treatment for patients with HFpEF, according to the 2019 opinion published by Dr. Butler and Dr. Packer. Once again a post hoc analysis, this time using data from TOPCAT, suggested a benefit from the mineralocorticoid receptor antagonist spironolactone in patients with heart failure and an EF of 45%-49% (45% was the minimum EF for enrollment into the study).
Recently, data from a third trial that tested sacubitril/valsartan in patients with HFpEF, PARAGON-HF, showed benefit among patients with EFs below the study median of 57%. This finding led the Food and Drug Administration in February 2021 to amend its initial approval for sacubitril/valsartan by removing a specific EF ceiling from the drug’s indication and instead saying that patient’s receiving the drug should have a “below normal” EF.
Writing in a recent commentary, Dr. Yancy called the FDA’s action on sacubitril/valsartan “reasonable,” and that the subgroup assessment of data from the PARAGON-HF trial creates a “new, reasonably evidence-based therapy for HFpEF.” He also predicted that guideline-writing panels will “likely align with a permissive statement of indication” for sacubitril/valsartan in patients with HFpEF, especially those with EFs of less than 57%.
The idea of using an SGLT2 inhibitor like empagliflozin on all heart failure patients, and also adding agents like sacubitril/valsartan and spironolactone in patients with HFpEF and EFs in the mid-50% range or lower may take some time to catch on, but it already has one influential advocate.
“If a patient has HFpEF with an EF of less than 55%, use quadruple-class therapy,” summed up Dr. Butler during the HFSA session, while also suggesting prescribing an SGLT2 inhibitor to essentially all patients with heart failure regardless of their EF.
The EMPEROR-Preserved and EMPEROR-Reduced trials and the EMPEROR-Pooled analysis were sponsored by Boehringer Ingelheim and Lilly, the companies that jointly market empagliflozin (Jardiance). Dr. Packer has had financial relationships with BI and Lilly and numerous other companies. Dr. Konstam has served on data monitoring committees for trials funded by Boehringer Ingelheim and by Amgen, Luitpold, and Pfizer, and has been a consultant to Arena, LivaNova, Merck, SC Pharma, and Takeda. Dr. Yancy had no disclosures. Dr. Butler has had financial relationships with Boehringer Ingelheim and numerous other companies.
FROM HFSA 2021
A new weight loss threshold for T2d remission after bariatric surgery?
Patients with type 2 diabetes who underwent bariatric surgery commonly experienced remission, but there was little increase in rates of remission above a threshold of 20% total weight loss (TWL), according to a retrospective analysis of 5,928 patients with diabetes in an integrated health care system in Southern California.
The findings should reassure physicians and patients that surgery will be beneficial, according to lead author Karen Coleman, PhD, professor of health systems science at Kaiser Permanente Southern California.
Dr. Coleman has heard from many physicians saying they recommend against bariatric surgery because of concerns that patients gain weight back and therefore won’t get a long-term benefit, but this is not supported by the literature. “Hundreds of articles at this point show that this simply is not true. In addition, providers seem to think about bariatric surgery as an ‘all or none’ treatment. Gaining any weight back means that patients ‘fail.’ Weight regain is a normal part of massive weight loss; however, maintaining a certain amount of weight loss still provides benefits for patients, especially those with cardiovascular conditions like diabetes,” said Dr. Coleman.
Most patients lose 20%-30% of their body weight after bariatric surgery, but they don’t have to lose that much to see an improvement in type 2 diabetes (T2D). In addition, if patients lose that much or more, and then gain some weight back, it doesn’t eliminate benefit. “Although we did not measure weight regain, a corollary statement is that patients can regain some of the weight they lose, but if they stay around 20% of their total weight lost, then their diabetes still remits,” said Dr. Coleman.
In the past, some standards to treat severe weight loss and metabolic disease called for 50% or more TWL. More recent standards target a 30% threshold. “We want physicians to understand that they need to have more reasonable expectations of weight loss with surgery and that these reasonable expectations still result in profound improvements in cardiovascular risk, death, and quality of life. A 20% TWL threshold is easier for these patients to get to, and like other patients, they still get the benefit. So even if these patients may not have as much weight loss they can still benefit from the surgery for their diabetes,” Dr. Coleman added.
Physicians have long assumed that the effect of bariatric surgery on T2D remission is tied to weight loss, but this has been tested only recently. Previous studies found a link and suggested that 25% TWL may be the needed threshold, but more data are needed, especially for sleeve gastrectomy.
In the current study, published in Diabetes Care, 73% of patients were female. Mean age was 49.8 years, and mean body mass index was 43.8 kg/m2. Fifty-seven percent underwent Roux-en-Y gastric bypass (RYGB). Follow-up averaged 5.9 years. Overall, 71% of patients had an initial remission of their diabetes (72% RYGB, 70% sleeve). The average time to remission was 1.0 years. The researchers categorized participants by percentage TWL. Compared with the 0%-5% group, each 5% increase in TWL was linked with a greater likelihood of achieving remission: 5%-10%, hazard ratio 1.22 (P = .23); 10%-15%, HR 1.97 (95% confidence interval, 1.47-2.64); 15%-20%, HR 2.33 (95% CI, 1.74-3.11); 20%-25%, HR 2.81 (95% CI, 2.11-3.75); 25%-30%, HR 2.88 (95% CI, 2.16-3.83); >30%, HR, 2.92 (95% CI, 2.19-3.88). Categories above 25% TWL had remission rates similar to those of the 20%-25% group. Those in the over 20% TWL group who were taking insulin at the time of surgery had better odds of T2D remission than did those in the 0%-5% TWL group who were not taking insulin (HR, 2.18; 95% CI, 1.64-2.88).
The study is a useful addition to the literature on the topic, according to W. Timothy Garvey, MD, director of the diabetes research center at the University of Alabama at Birmingham. “This tends to quantify it a little bit more than people might have had before,” he said.
Dr. Garvey noted that there were wide error bars in the outcomes grouped by TWL, and suggested that individual results of surgery may vary widely. “There are plenty of individuals in each of those bins that will require more weight loss for remission or less weight loss. That’s just the average of people in that weight loss category. So if a clinician is going to use this information, they need to take it with a grain of salt and realize that, just because they reach that 20% weight loss threshold, it doesn’t mean that their patient is going to go into remission. As a loose guide, as something to shoot for, I think this is valuable,” he added.
Dr. Coleman recommended that physicians not wait too long to suggest bariatric surgery, since patients are likely to have better outcomes if they are healthier going in. “Bariatric surgery is by far the most effective long-term treatment we have for severe obesity and we should be treating it as a secondary prevention strategy, not a last resort to save people’s lives. Bariatric surgery cannot regrow the cells in the pancreas that make insulin. So if we wait until patients with type 2 diabetes are insulin dependent to offer bariatric surgery, we are compromising the great effect surgery can have for them,” said Dr. Coleman.
Patients with type 2 diabetes who underwent bariatric surgery commonly experienced remission, but there was little increase in rates of remission above a threshold of 20% total weight loss (TWL), according to a retrospective analysis of 5,928 patients with diabetes in an integrated health care system in Southern California.
The findings should reassure physicians and patients that surgery will be beneficial, according to lead author Karen Coleman, PhD, professor of health systems science at Kaiser Permanente Southern California.
Dr. Coleman has heard from many physicians saying they recommend against bariatric surgery because of concerns that patients gain weight back and therefore won’t get a long-term benefit, but this is not supported by the literature. “Hundreds of articles at this point show that this simply is not true. In addition, providers seem to think about bariatric surgery as an ‘all or none’ treatment. Gaining any weight back means that patients ‘fail.’ Weight regain is a normal part of massive weight loss; however, maintaining a certain amount of weight loss still provides benefits for patients, especially those with cardiovascular conditions like diabetes,” said Dr. Coleman.
Most patients lose 20%-30% of their body weight after bariatric surgery, but they don’t have to lose that much to see an improvement in type 2 diabetes (T2D). In addition, if patients lose that much or more, and then gain some weight back, it doesn’t eliminate benefit. “Although we did not measure weight regain, a corollary statement is that patients can regain some of the weight they lose, but if they stay around 20% of their total weight lost, then their diabetes still remits,” said Dr. Coleman.
In the past, some standards to treat severe weight loss and metabolic disease called for 50% or more TWL. More recent standards target a 30% threshold. “We want physicians to understand that they need to have more reasonable expectations of weight loss with surgery and that these reasonable expectations still result in profound improvements in cardiovascular risk, death, and quality of life. A 20% TWL threshold is easier for these patients to get to, and like other patients, they still get the benefit. So even if these patients may not have as much weight loss they can still benefit from the surgery for their diabetes,” Dr. Coleman added.
Physicians have long assumed that the effect of bariatric surgery on T2D remission is tied to weight loss, but this has been tested only recently. Previous studies found a link and suggested that 25% TWL may be the needed threshold, but more data are needed, especially for sleeve gastrectomy.
In the current study, published in Diabetes Care, 73% of patients were female. Mean age was 49.8 years, and mean body mass index was 43.8 kg/m2. Fifty-seven percent underwent Roux-en-Y gastric bypass (RYGB). Follow-up averaged 5.9 years. Overall, 71% of patients had an initial remission of their diabetes (72% RYGB, 70% sleeve). The average time to remission was 1.0 years. The researchers categorized participants by percentage TWL. Compared with the 0%-5% group, each 5% increase in TWL was linked with a greater likelihood of achieving remission: 5%-10%, hazard ratio 1.22 (P = .23); 10%-15%, HR 1.97 (95% confidence interval, 1.47-2.64); 15%-20%, HR 2.33 (95% CI, 1.74-3.11); 20%-25%, HR 2.81 (95% CI, 2.11-3.75); 25%-30%, HR 2.88 (95% CI, 2.16-3.83); >30%, HR, 2.92 (95% CI, 2.19-3.88). Categories above 25% TWL had remission rates similar to those of the 20%-25% group. Those in the over 20% TWL group who were taking insulin at the time of surgery had better odds of T2D remission than did those in the 0%-5% TWL group who were not taking insulin (HR, 2.18; 95% CI, 1.64-2.88).
The study is a useful addition to the literature on the topic, according to W. Timothy Garvey, MD, director of the diabetes research center at the University of Alabama at Birmingham. “This tends to quantify it a little bit more than people might have had before,” he said.
Dr. Garvey noted that there were wide error bars in the outcomes grouped by TWL, and suggested that individual results of surgery may vary widely. “There are plenty of individuals in each of those bins that will require more weight loss for remission or less weight loss. That’s just the average of people in that weight loss category. So if a clinician is going to use this information, they need to take it with a grain of salt and realize that, just because they reach that 20% weight loss threshold, it doesn’t mean that their patient is going to go into remission. As a loose guide, as something to shoot for, I think this is valuable,” he added.
Dr. Coleman recommended that physicians not wait too long to suggest bariatric surgery, since patients are likely to have better outcomes if they are healthier going in. “Bariatric surgery is by far the most effective long-term treatment we have for severe obesity and we should be treating it as a secondary prevention strategy, not a last resort to save people’s lives. Bariatric surgery cannot regrow the cells in the pancreas that make insulin. So if we wait until patients with type 2 diabetes are insulin dependent to offer bariatric surgery, we are compromising the great effect surgery can have for them,” said Dr. Coleman.
Patients with type 2 diabetes who underwent bariatric surgery commonly experienced remission, but there was little increase in rates of remission above a threshold of 20% total weight loss (TWL), according to a retrospective analysis of 5,928 patients with diabetes in an integrated health care system in Southern California.
The findings should reassure physicians and patients that surgery will be beneficial, according to lead author Karen Coleman, PhD, professor of health systems science at Kaiser Permanente Southern California.
Dr. Coleman has heard from many physicians saying they recommend against bariatric surgery because of concerns that patients gain weight back and therefore won’t get a long-term benefit, but this is not supported by the literature. “Hundreds of articles at this point show that this simply is not true. In addition, providers seem to think about bariatric surgery as an ‘all or none’ treatment. Gaining any weight back means that patients ‘fail.’ Weight regain is a normal part of massive weight loss; however, maintaining a certain amount of weight loss still provides benefits for patients, especially those with cardiovascular conditions like diabetes,” said Dr. Coleman.
Most patients lose 20%-30% of their body weight after bariatric surgery, but they don’t have to lose that much to see an improvement in type 2 diabetes (T2D). In addition, if patients lose that much or more, and then gain some weight back, it doesn’t eliminate benefit. “Although we did not measure weight regain, a corollary statement is that patients can regain some of the weight they lose, but if they stay around 20% of their total weight lost, then their diabetes still remits,” said Dr. Coleman.
In the past, some standards to treat severe weight loss and metabolic disease called for 50% or more TWL. More recent standards target a 30% threshold. “We want physicians to understand that they need to have more reasonable expectations of weight loss with surgery and that these reasonable expectations still result in profound improvements in cardiovascular risk, death, and quality of life. A 20% TWL threshold is easier for these patients to get to, and like other patients, they still get the benefit. So even if these patients may not have as much weight loss they can still benefit from the surgery for their diabetes,” Dr. Coleman added.
Physicians have long assumed that the effect of bariatric surgery on T2D remission is tied to weight loss, but this has been tested only recently. Previous studies found a link and suggested that 25% TWL may be the needed threshold, but more data are needed, especially for sleeve gastrectomy.
In the current study, published in Diabetes Care, 73% of patients were female. Mean age was 49.8 years, and mean body mass index was 43.8 kg/m2. Fifty-seven percent underwent Roux-en-Y gastric bypass (RYGB). Follow-up averaged 5.9 years. Overall, 71% of patients had an initial remission of their diabetes (72% RYGB, 70% sleeve). The average time to remission was 1.0 years. The researchers categorized participants by percentage TWL. Compared with the 0%-5% group, each 5% increase in TWL was linked with a greater likelihood of achieving remission: 5%-10%, hazard ratio 1.22 (P = .23); 10%-15%, HR 1.97 (95% confidence interval, 1.47-2.64); 15%-20%, HR 2.33 (95% CI, 1.74-3.11); 20%-25%, HR 2.81 (95% CI, 2.11-3.75); 25%-30%, HR 2.88 (95% CI, 2.16-3.83); >30%, HR, 2.92 (95% CI, 2.19-3.88). Categories above 25% TWL had remission rates similar to those of the 20%-25% group. Those in the over 20% TWL group who were taking insulin at the time of surgery had better odds of T2D remission than did those in the 0%-5% TWL group who were not taking insulin (HR, 2.18; 95% CI, 1.64-2.88).
The study is a useful addition to the literature on the topic, according to W. Timothy Garvey, MD, director of the diabetes research center at the University of Alabama at Birmingham. “This tends to quantify it a little bit more than people might have had before,” he said.
Dr. Garvey noted that there were wide error bars in the outcomes grouped by TWL, and suggested that individual results of surgery may vary widely. “There are plenty of individuals in each of those bins that will require more weight loss for remission or less weight loss. That’s just the average of people in that weight loss category. So if a clinician is going to use this information, they need to take it with a grain of salt and realize that, just because they reach that 20% weight loss threshold, it doesn’t mean that their patient is going to go into remission. As a loose guide, as something to shoot for, I think this is valuable,” he added.
Dr. Coleman recommended that physicians not wait too long to suggest bariatric surgery, since patients are likely to have better outcomes if they are healthier going in. “Bariatric surgery is by far the most effective long-term treatment we have for severe obesity and we should be treating it as a secondary prevention strategy, not a last resort to save people’s lives. Bariatric surgery cannot regrow the cells in the pancreas that make insulin. So if we wait until patients with type 2 diabetes are insulin dependent to offer bariatric surgery, we are compromising the great effect surgery can have for them,” said Dr. Coleman.
FROM DIABETES CARE
Moderna vaccine more effective than Pfizer and J&J
the Centers for Disease Control and Protection has said.
“Among U.S. adults without immunocompromising conditions, vaccine effectiveness against COVID-19 hospitalization during March 11–Aug. 15, 2021, was higher for the Moderna vaccine (93%) than the Pfizer-BioNTech vaccine (88%) and the Janssen vaccine (71%),” the agency’s Morbidity and Mortality Weekly Report said. Janssen refers to the Johnson & Johnson vaccine.
The CDC said the data could help people make informed decisions.
“Understanding differences in VE [vaccine effectiveness] by vaccine product can guide individual choices and policy recommendations regarding vaccine boosters. All Food and Drug Administration–approved or authorized COVID-19 vaccines provide substantial protection against COVID-19 hospitalization,” the report said.
The study also broke down effectiveness for longer periods. Moderna came out on top again.
After 120 days, the Moderna vaccine provided 92% effectiveness against hospitalization, whereas the Pfizer vaccine’s effectiveness dropped to 77%, the CDC said. There was no similar calculation for the Johnson & Johnson vaccine.
The CDC studied 3,689 adults at 21 hospitals in 18 states who got the two-shot Pfizer or Moderna vaccine or the one-shot Johnson & Johnson vaccine between March and August.
The agency noted some factors that could have come into play.
“Differences in vaccine effectiveness between the Moderna and Pfizer-BioNTech vaccine might be due to higher mRNA content in the Moderna vaccine, differences in timing between doses (3 weeks for Pfizer-BioNTech vs. 4 weeks for Moderna), or possible differences between groups that received each vaccine that were not accounted for in the analysis,” the report said.
The CDC noted limitations in the findings. Children, immunocompromised adults, and vaccine effectiveness against COVID-19 that did not result in hospitalization were not studied.
Other studies have shown all three U.S. vaccines provide a high rate of protection against coronavirus.
A version of this article first appeared on WebMD.com.
the Centers for Disease Control and Protection has said.
“Among U.S. adults without immunocompromising conditions, vaccine effectiveness against COVID-19 hospitalization during March 11–Aug. 15, 2021, was higher for the Moderna vaccine (93%) than the Pfizer-BioNTech vaccine (88%) and the Janssen vaccine (71%),” the agency’s Morbidity and Mortality Weekly Report said. Janssen refers to the Johnson & Johnson vaccine.
The CDC said the data could help people make informed decisions.
“Understanding differences in VE [vaccine effectiveness] by vaccine product can guide individual choices and policy recommendations regarding vaccine boosters. All Food and Drug Administration–approved or authorized COVID-19 vaccines provide substantial protection against COVID-19 hospitalization,” the report said.
The study also broke down effectiveness for longer periods. Moderna came out on top again.
After 120 days, the Moderna vaccine provided 92% effectiveness against hospitalization, whereas the Pfizer vaccine’s effectiveness dropped to 77%, the CDC said. There was no similar calculation for the Johnson & Johnson vaccine.
The CDC studied 3,689 adults at 21 hospitals in 18 states who got the two-shot Pfizer or Moderna vaccine or the one-shot Johnson & Johnson vaccine between March and August.
The agency noted some factors that could have come into play.
“Differences in vaccine effectiveness between the Moderna and Pfizer-BioNTech vaccine might be due to higher mRNA content in the Moderna vaccine, differences in timing between doses (3 weeks for Pfizer-BioNTech vs. 4 weeks for Moderna), or possible differences between groups that received each vaccine that were not accounted for in the analysis,” the report said.
The CDC noted limitations in the findings. Children, immunocompromised adults, and vaccine effectiveness against COVID-19 that did not result in hospitalization were not studied.
Other studies have shown all three U.S. vaccines provide a high rate of protection against coronavirus.
A version of this article first appeared on WebMD.com.
the Centers for Disease Control and Protection has said.
“Among U.S. adults without immunocompromising conditions, vaccine effectiveness against COVID-19 hospitalization during March 11–Aug. 15, 2021, was higher for the Moderna vaccine (93%) than the Pfizer-BioNTech vaccine (88%) and the Janssen vaccine (71%),” the agency’s Morbidity and Mortality Weekly Report said. Janssen refers to the Johnson & Johnson vaccine.
The CDC said the data could help people make informed decisions.
“Understanding differences in VE [vaccine effectiveness] by vaccine product can guide individual choices and policy recommendations regarding vaccine boosters. All Food and Drug Administration–approved or authorized COVID-19 vaccines provide substantial protection against COVID-19 hospitalization,” the report said.
The study also broke down effectiveness for longer periods. Moderna came out on top again.
After 120 days, the Moderna vaccine provided 92% effectiveness against hospitalization, whereas the Pfizer vaccine’s effectiveness dropped to 77%, the CDC said. There was no similar calculation for the Johnson & Johnson vaccine.
The CDC studied 3,689 adults at 21 hospitals in 18 states who got the two-shot Pfizer or Moderna vaccine or the one-shot Johnson & Johnson vaccine between March and August.
The agency noted some factors that could have come into play.
“Differences in vaccine effectiveness between the Moderna and Pfizer-BioNTech vaccine might be due to higher mRNA content in the Moderna vaccine, differences in timing between doses (3 weeks for Pfizer-BioNTech vs. 4 weeks for Moderna), or possible differences between groups that received each vaccine that were not accounted for in the analysis,” the report said.
The CDC noted limitations in the findings. Children, immunocompromised adults, and vaccine effectiveness against COVID-19 that did not result in hospitalization were not studied.
Other studies have shown all three U.S. vaccines provide a high rate of protection against coronavirus.
A version of this article first appeared on WebMD.com.
Transfusions, readmissions higher for patients with CLL after cardiac surgery
Patients with chronic lymphocytic leukemia have similar outcomes following cardiac operations as patients without CLL, but commonly require more blood transfusions, according to the results of retrospective cohort study using the 2010-2017 Nationwide Readmissions Database (NRD).
The researchers assessed all adult patients undergoing elective coronary artery bypass grafting, valve repair, or valve replacement as identified using the NRD.
Patients were stratified by history of CLL and the incidence of in-hospital mortality, perioperative complications, blood transfusions, and readmission within 90 days were examined. A 3:1 nearest-neighbor matching was performed between patients with and without CLL for all primary and secondary outcomes of interest, according to the report, published online in Annals of Thoracic Surgery.
Comparable results
A total of 1,250,882 patients in the database were found who underwent cardiac operations. Of these, 0.23% had a diagnosis of CLL. Among 11,237 propensity-matched patients, those with CLL had similar rates of in-hospital mortality (3.8% vs. 2.6%, P = .08) and perioperative complications (33.4% vs. 33.6%, P = .92), compared with their non-CLL counterparts. However, the incidence of infection was comparable (8.5% vs. 9.4%, P = .38).
However, patients with CLL required blood transfusions more frequently (33.7% vs. 28.4%, P = .003) than did patients without CLL. In addition, patients with CLL were more likely to be readmitted within 90 days of discharge, compared with their counterparts, and “respiratory reasons, including pneumonia, contributed significantly to the readmission burden in this cohort,” the researchers, led by Josef Madrigal, BS, of the University of California, Los Angeles, stated.
“The inherent risk of transfusion and the possible benefits of blood conservation interventions must be considered in this patient population. Increased risk of rehospitalization in patients with CLL suggests the need for measures aimed at mitigating the risk of respiratory complications,” the researchers concluded.
There were no conflicts of interest reported in the article.
Patients with chronic lymphocytic leukemia have similar outcomes following cardiac operations as patients without CLL, but commonly require more blood transfusions, according to the results of retrospective cohort study using the 2010-2017 Nationwide Readmissions Database (NRD).
The researchers assessed all adult patients undergoing elective coronary artery bypass grafting, valve repair, or valve replacement as identified using the NRD.
Patients were stratified by history of CLL and the incidence of in-hospital mortality, perioperative complications, blood transfusions, and readmission within 90 days were examined. A 3:1 nearest-neighbor matching was performed between patients with and without CLL for all primary and secondary outcomes of interest, according to the report, published online in Annals of Thoracic Surgery.
Comparable results
A total of 1,250,882 patients in the database were found who underwent cardiac operations. Of these, 0.23% had a diagnosis of CLL. Among 11,237 propensity-matched patients, those with CLL had similar rates of in-hospital mortality (3.8% vs. 2.6%, P = .08) and perioperative complications (33.4% vs. 33.6%, P = .92), compared with their non-CLL counterparts. However, the incidence of infection was comparable (8.5% vs. 9.4%, P = .38).
However, patients with CLL required blood transfusions more frequently (33.7% vs. 28.4%, P = .003) than did patients without CLL. In addition, patients with CLL were more likely to be readmitted within 90 days of discharge, compared with their counterparts, and “respiratory reasons, including pneumonia, contributed significantly to the readmission burden in this cohort,” the researchers, led by Josef Madrigal, BS, of the University of California, Los Angeles, stated.
“The inherent risk of transfusion and the possible benefits of blood conservation interventions must be considered in this patient population. Increased risk of rehospitalization in patients with CLL suggests the need for measures aimed at mitigating the risk of respiratory complications,” the researchers concluded.
There were no conflicts of interest reported in the article.
Patients with chronic lymphocytic leukemia have similar outcomes following cardiac operations as patients without CLL, but commonly require more blood transfusions, according to the results of retrospective cohort study using the 2010-2017 Nationwide Readmissions Database (NRD).
The researchers assessed all adult patients undergoing elective coronary artery bypass grafting, valve repair, or valve replacement as identified using the NRD.
Patients were stratified by history of CLL and the incidence of in-hospital mortality, perioperative complications, blood transfusions, and readmission within 90 days were examined. A 3:1 nearest-neighbor matching was performed between patients with and without CLL for all primary and secondary outcomes of interest, according to the report, published online in Annals of Thoracic Surgery.
Comparable results
A total of 1,250,882 patients in the database were found who underwent cardiac operations. Of these, 0.23% had a diagnosis of CLL. Among 11,237 propensity-matched patients, those with CLL had similar rates of in-hospital mortality (3.8% vs. 2.6%, P = .08) and perioperative complications (33.4% vs. 33.6%, P = .92), compared with their non-CLL counterparts. However, the incidence of infection was comparable (8.5% vs. 9.4%, P = .38).
However, patients with CLL required blood transfusions more frequently (33.7% vs. 28.4%, P = .003) than did patients without CLL. In addition, patients with CLL were more likely to be readmitted within 90 days of discharge, compared with their counterparts, and “respiratory reasons, including pneumonia, contributed significantly to the readmission burden in this cohort,” the researchers, led by Josef Madrigal, BS, of the University of California, Los Angeles, stated.
“The inherent risk of transfusion and the possible benefits of blood conservation interventions must be considered in this patient population. Increased risk of rehospitalization in patients with CLL suggests the need for measures aimed at mitigating the risk of respiratory complications,” the researchers concluded.
There were no conflicts of interest reported in the article.
FROM THE ANNALS OF THORACIC SURGERY
FDA panel backs Pfizer's COVID booster for 65 and older, those at high risk
An expert panel that advises the Food and Drug Administration on its regulatory decisions voted Sept. 17 against recommending third doses of Pfizer’s COVID-19 vaccine for younger Americans.
But they didn’t kill the idea of booster shots completely.
In a dramatic, last-minute pivot, the 18 members of the FDA’s Vaccines and Related Biological Products Advisory Committee unanimously voted to recommend the FDA make boosters available for seniors and others at high risk of severe outcomes from COVID-19, including health care workers.
The 16-2 vote was a rebuttal to Pfizer’s initial request. The company had asked the FDA to allow it to offer third doses to all Americans over the age of 16 at least six months after their second shot.
The company requested an amendment to the full approval the FDA granted in August. That is the typical way boosters are authorized in the U.S., but it requires a higher bar of evidence and more regulatory scrutiny than the agency had been able to give since Pfizer filed for the change just days after its vaccine was granted full approval.
The committee’s actions were also a rebuff to the Biden administration, which announced before the FDA approved them that boosters would be rolled out to the general public Sept. 20. The announcement triggered the resignations of two of the agency’s top vaccine reviewers, who both participated in the Sept. 17 meeting.
After initially voting against Pfizer’s request to amend its license, the committee then worked on the fly with FDA officials to craft a strategy that would allow third doses to be offered under an emergency use authorization (EUA).
An EUA requires a lower standard of evidence and is more specific. It will restrict third doses to a more defined population than a change to the license would. It will also require Pfizer to continue to monitor the safety of third doses as they begin to be administered.
“This should demonstrate to the public that the members of this committee are independent of the FDA and that we do, in fact, bring our voices to the table when we are asked to serve on this committee,” said Archana Chattergee, MD, a pediatric infectious disease specialist who is dean of the Chicago Medical School at Rosalind Franklin University in Illinois.
The FDA doesn’t have to follow the committee’s recommendation, but almost certainly will, though regulators said they may still make some changes.
“We are not bound at FDA by your vote, we can tweak this,” said Peter Marks, MD, director of the Center for Biologics Evaluation and Research at the FDA. Dr. Marks participated in the meeting and helped to draft the revised proposal.
If the FDA issues the recommended EUA, a council of independent advisors to the CDC will make specific recommendations about how the third doses should be given. After the CDC director weighs in, boosters will begin rolling out to the public.
Moderna submitted data to the FDA on Sept. 1 in support of adding a booster dose to its regimen. The agency has not yet scheduled a public review of that data.
The Biden administration is prepared to administer shots as soon as they get the green light, Surgeon General Vivek Murthy, MD, said at a White House briefing earlier Sept. 17.
"This process is consistent with what we outlined in August where our goals were to stay ahead of the virus," Dr. Murthy said. "Our goal then and now is to protect the health and well-being of the public. As soon as the FDA and CDC complete their evaluations, we will be ready to move forward accordingly."
He added, "We've used this time since our August announcement to communicate and coordinate with pharmacy partners, nursing homes, states, and localities."
White House COVID-19 Response Coordinator Jeff Zients said vaccine supply is "in good shape for all Americans to get boosters as recommended."
Taking cues from Israel
In considering Pfizer’s original request, the committee overwhelmingly felt that they didn’t have enough information to say that the benefits of an additional dose of vaccine in 16- and 17-year-olds would outweigh its risk. Teens have the highest risk of rare heart inflammation after vaccination, a side effect known as myocarditis. It is not known how the vaccines are causing these cases of heart swelling. Most who have been diagnosed with the condition have recovered, though some have needed hospital care.
Pfizer didn’t include 16- and 17-year-olds in its studies of boosters, which included about 300 people between the ages of 18 and 55. The company acknowledged that gap in its data but pointed to FDA guidance that said evidence from adults could be extrapolated to teens.
“We don’t know that much about risks,” said committee member Eric Rubin, MD, who is editor-in-chief of the New England Journal of Medicine.
Much of the data on the potential benefits and harms of third Pfizer doses comes from Israel, which first began rolling out boosters to older adults in July.
In a highly anticipated presentation, Sharon Alroy-Preis, Israel’s director of public health services, joined the meeting to describe Israel’s experience with boosters.
Israel began to see a third surge of COVID-19 cases in December.
“This was after having two waves and two lockdowns,” Ms. Alroy-Preis said. By the third surge, she said, Israelis were tired.
“We decided on a lockdown, but the compliance of the public wasn’t as it was in the previous two waves,” she said.
Then the vaccine arrived. Israel started vaccinations as soon as the FDA approved it, and they quickly vaccinated a high percentage of their population, about 3 months faster than the rest of the world.
All vaccinations are reported and tracked by the Ministry of Health, so the country is able to keep close tabs on how well the shots are working.
As vaccines rolled out, cases fell dramatically. The pandemic seemed to be behind them. Delta arrived in March. By June, their cases were doubling every 10 days, despite about 80% of their most vulnerable adults being fully vaccinated, she said.
Most concerning was that about 60% of severe cases were breakthrough cases in fully vaccinated individuals.
“We had to stop and figure out, was this a Delta issue,” she said. “Or was this a waning immunity issue.”
“We had some clue that it might not be the Delta variant, at least not alone,” she said.
People who had originally been first in line for the vaccines, seniors and health care workers, were having the highest rates of breakthrough infections. People further away from their second dose were more likely to get a breakthrough infection.
Ms. Alroy-Preis said that if they had not started booster doses in July, their hospitals would have been overwhelmed. They had projected that they would have 2,000 cases in the hospital each day.
Boosters have helped to flatten the curve, though they are still seeing a significant number of infections.
Data from Israel presented at the meeting show boosters are largely safe and effective at reducing severe outcomes in seniors. Israeli experience also showed that third doses, which generate very high levels of neutralizing antibodies—the first and fastest line of the body’s immune defense - -may also slow transmission of the virus.
Key differences in the U.S.
The benefit of slowing down the explosive spread of a highly contagious virus was tantalizing, but many members noted that circumstances in Israel are very different than in the United States. Israel went into its current Delta surge already having high levels of vaccination in its population. They also relied on the Pfizer vaccine almost exclusively for their campaign.
The United States used a different mix of vaccines – Pfizer, Moderna, and Johnson & Johnson -- and doesn’t have the same high level of vaccination coverage of its population.
In the United States, transmission is mainly being driven by unvaccinated people, Dr. Rubin noted.
“That really means the primary benefit is going to be in reducing disease,” he said, “And we know the people who are going to benefit from that … and those are the kinds of people the FDA has already approved a third dose for,” he said, referring to those with underlying health conditions.
But Israel only began vaccinating younger people a few weeks ago. Most are still within a window where rare risks like myocarditis could appear, Rubin noted.
He and other members of the committee said they wished they had more information about the safety of third doses in younger adults.
“We don’t have that right now, and I don’t think I would be comfortable giving it to a 16-year-old,” he said.
At the same time, the primary benefit for third doses would be in preventing severe disease, and overall, data from the United States and other countries show that two doses of the vaccines remain highly effective at preventing hospitalization and death.
Asked why Israel began to see more severe cases in fully vaccinated people, the CDC’s Sara Oliver, MD, a disease detective with the CDC, said it was probably due to a mix of factors including the fact that Israel defines severe cases a little differently.
In the United States, a severe case is generally a person who has to be hospitalized or who has died from the infection. In Israel, a person with a severe case is someone who has an elevated respiratory rate and someone who has a blood oxygen level less than 94%. In the United States, that kind of patient wouldn’t necessarily be hospitalized.
In the end, one of the two committee members who wanted full approval for Pfizer’s third doses said he was satisfied with the outcome.
Mark Sawyer, MD, a professor of pediatrics and infectious disease at the University of California at San Diego, said he voted yes on the first question because he thought full approval was the best way to give doctors the flexibility to prescribe the shots to vulnerable individuals.
“I’m really glad we authorized a vaccine for a third dose, and I plan to go out and get my vaccine this afternoon,” Dr. Sawyer said, noting that he was at high risk as a health care provider.
This article was updated 9/19/21.
A version of this article first appeared on Medscape.com.
An expert panel that advises the Food and Drug Administration on its regulatory decisions voted Sept. 17 against recommending third doses of Pfizer’s COVID-19 vaccine for younger Americans.
But they didn’t kill the idea of booster shots completely.
In a dramatic, last-minute pivot, the 18 members of the FDA’s Vaccines and Related Biological Products Advisory Committee unanimously voted to recommend the FDA make boosters available for seniors and others at high risk of severe outcomes from COVID-19, including health care workers.
The 16-2 vote was a rebuttal to Pfizer’s initial request. The company had asked the FDA to allow it to offer third doses to all Americans over the age of 16 at least six months after their second shot.
The company requested an amendment to the full approval the FDA granted in August. That is the typical way boosters are authorized in the U.S., but it requires a higher bar of evidence and more regulatory scrutiny than the agency had been able to give since Pfizer filed for the change just days after its vaccine was granted full approval.
The committee’s actions were also a rebuff to the Biden administration, which announced before the FDA approved them that boosters would be rolled out to the general public Sept. 20. The announcement triggered the resignations of two of the agency’s top vaccine reviewers, who both participated in the Sept. 17 meeting.
After initially voting against Pfizer’s request to amend its license, the committee then worked on the fly with FDA officials to craft a strategy that would allow third doses to be offered under an emergency use authorization (EUA).
An EUA requires a lower standard of evidence and is more specific. It will restrict third doses to a more defined population than a change to the license would. It will also require Pfizer to continue to monitor the safety of third doses as they begin to be administered.
“This should demonstrate to the public that the members of this committee are independent of the FDA and that we do, in fact, bring our voices to the table when we are asked to serve on this committee,” said Archana Chattergee, MD, a pediatric infectious disease specialist who is dean of the Chicago Medical School at Rosalind Franklin University in Illinois.
The FDA doesn’t have to follow the committee’s recommendation, but almost certainly will, though regulators said they may still make some changes.
“We are not bound at FDA by your vote, we can tweak this,” said Peter Marks, MD, director of the Center for Biologics Evaluation and Research at the FDA. Dr. Marks participated in the meeting and helped to draft the revised proposal.
If the FDA issues the recommended EUA, a council of independent advisors to the CDC will make specific recommendations about how the third doses should be given. After the CDC director weighs in, boosters will begin rolling out to the public.
Moderna submitted data to the FDA on Sept. 1 in support of adding a booster dose to its regimen. The agency has not yet scheduled a public review of that data.
The Biden administration is prepared to administer shots as soon as they get the green light, Surgeon General Vivek Murthy, MD, said at a White House briefing earlier Sept. 17.
"This process is consistent with what we outlined in August where our goals were to stay ahead of the virus," Dr. Murthy said. "Our goal then and now is to protect the health and well-being of the public. As soon as the FDA and CDC complete their evaluations, we will be ready to move forward accordingly."
He added, "We've used this time since our August announcement to communicate and coordinate with pharmacy partners, nursing homes, states, and localities."
White House COVID-19 Response Coordinator Jeff Zients said vaccine supply is "in good shape for all Americans to get boosters as recommended."
Taking cues from Israel
In considering Pfizer’s original request, the committee overwhelmingly felt that they didn’t have enough information to say that the benefits of an additional dose of vaccine in 16- and 17-year-olds would outweigh its risk. Teens have the highest risk of rare heart inflammation after vaccination, a side effect known as myocarditis. It is not known how the vaccines are causing these cases of heart swelling. Most who have been diagnosed with the condition have recovered, though some have needed hospital care.
Pfizer didn’t include 16- and 17-year-olds in its studies of boosters, which included about 300 people between the ages of 18 and 55. The company acknowledged that gap in its data but pointed to FDA guidance that said evidence from adults could be extrapolated to teens.
“We don’t know that much about risks,” said committee member Eric Rubin, MD, who is editor-in-chief of the New England Journal of Medicine.
Much of the data on the potential benefits and harms of third Pfizer doses comes from Israel, which first began rolling out boosters to older adults in July.
In a highly anticipated presentation, Sharon Alroy-Preis, Israel’s director of public health services, joined the meeting to describe Israel’s experience with boosters.
Israel began to see a third surge of COVID-19 cases in December.
“This was after having two waves and two lockdowns,” Ms. Alroy-Preis said. By the third surge, she said, Israelis were tired.
“We decided on a lockdown, but the compliance of the public wasn’t as it was in the previous two waves,” she said.
Then the vaccine arrived. Israel started vaccinations as soon as the FDA approved it, and they quickly vaccinated a high percentage of their population, about 3 months faster than the rest of the world.
All vaccinations are reported and tracked by the Ministry of Health, so the country is able to keep close tabs on how well the shots are working.
As vaccines rolled out, cases fell dramatically. The pandemic seemed to be behind them. Delta arrived in March. By June, their cases were doubling every 10 days, despite about 80% of their most vulnerable adults being fully vaccinated, she said.
Most concerning was that about 60% of severe cases were breakthrough cases in fully vaccinated individuals.
“We had to stop and figure out, was this a Delta issue,” she said. “Or was this a waning immunity issue.”
“We had some clue that it might not be the Delta variant, at least not alone,” she said.
People who had originally been first in line for the vaccines, seniors and health care workers, were having the highest rates of breakthrough infections. People further away from their second dose were more likely to get a breakthrough infection.
Ms. Alroy-Preis said that if they had not started booster doses in July, their hospitals would have been overwhelmed. They had projected that they would have 2,000 cases in the hospital each day.
Boosters have helped to flatten the curve, though they are still seeing a significant number of infections.
Data from Israel presented at the meeting show boosters are largely safe and effective at reducing severe outcomes in seniors. Israeli experience also showed that third doses, which generate very high levels of neutralizing antibodies—the first and fastest line of the body’s immune defense - -may also slow transmission of the virus.
Key differences in the U.S.
The benefit of slowing down the explosive spread of a highly contagious virus was tantalizing, but many members noted that circumstances in Israel are very different than in the United States. Israel went into its current Delta surge already having high levels of vaccination in its population. They also relied on the Pfizer vaccine almost exclusively for their campaign.
The United States used a different mix of vaccines – Pfizer, Moderna, and Johnson & Johnson -- and doesn’t have the same high level of vaccination coverage of its population.
In the United States, transmission is mainly being driven by unvaccinated people, Dr. Rubin noted.
“That really means the primary benefit is going to be in reducing disease,” he said, “And we know the people who are going to benefit from that … and those are the kinds of people the FDA has already approved a third dose for,” he said, referring to those with underlying health conditions.
But Israel only began vaccinating younger people a few weeks ago. Most are still within a window where rare risks like myocarditis could appear, Rubin noted.
He and other members of the committee said they wished they had more information about the safety of third doses in younger adults.
“We don’t have that right now, and I don’t think I would be comfortable giving it to a 16-year-old,” he said.
At the same time, the primary benefit for third doses would be in preventing severe disease, and overall, data from the United States and other countries show that two doses of the vaccines remain highly effective at preventing hospitalization and death.
Asked why Israel began to see more severe cases in fully vaccinated people, the CDC’s Sara Oliver, MD, a disease detective with the CDC, said it was probably due to a mix of factors including the fact that Israel defines severe cases a little differently.
In the United States, a severe case is generally a person who has to be hospitalized or who has died from the infection. In Israel, a person with a severe case is someone who has an elevated respiratory rate and someone who has a blood oxygen level less than 94%. In the United States, that kind of patient wouldn’t necessarily be hospitalized.
In the end, one of the two committee members who wanted full approval for Pfizer’s third doses said he was satisfied with the outcome.
Mark Sawyer, MD, a professor of pediatrics and infectious disease at the University of California at San Diego, said he voted yes on the first question because he thought full approval was the best way to give doctors the flexibility to prescribe the shots to vulnerable individuals.
“I’m really glad we authorized a vaccine for a third dose, and I plan to go out and get my vaccine this afternoon,” Dr. Sawyer said, noting that he was at high risk as a health care provider.
This article was updated 9/19/21.
A version of this article first appeared on Medscape.com.
An expert panel that advises the Food and Drug Administration on its regulatory decisions voted Sept. 17 against recommending third doses of Pfizer’s COVID-19 vaccine for younger Americans.
But they didn’t kill the idea of booster shots completely.
In a dramatic, last-minute pivot, the 18 members of the FDA’s Vaccines and Related Biological Products Advisory Committee unanimously voted to recommend the FDA make boosters available for seniors and others at high risk of severe outcomes from COVID-19, including health care workers.
The 16-2 vote was a rebuttal to Pfizer’s initial request. The company had asked the FDA to allow it to offer third doses to all Americans over the age of 16 at least six months after their second shot.
The company requested an amendment to the full approval the FDA granted in August. That is the typical way boosters are authorized in the U.S., but it requires a higher bar of evidence and more regulatory scrutiny than the agency had been able to give since Pfizer filed for the change just days after its vaccine was granted full approval.
The committee’s actions were also a rebuff to the Biden administration, which announced before the FDA approved them that boosters would be rolled out to the general public Sept. 20. The announcement triggered the resignations of two of the agency’s top vaccine reviewers, who both participated in the Sept. 17 meeting.
After initially voting against Pfizer’s request to amend its license, the committee then worked on the fly with FDA officials to craft a strategy that would allow third doses to be offered under an emergency use authorization (EUA).
An EUA requires a lower standard of evidence and is more specific. It will restrict third doses to a more defined population than a change to the license would. It will also require Pfizer to continue to monitor the safety of third doses as they begin to be administered.
“This should demonstrate to the public that the members of this committee are independent of the FDA and that we do, in fact, bring our voices to the table when we are asked to serve on this committee,” said Archana Chattergee, MD, a pediatric infectious disease specialist who is dean of the Chicago Medical School at Rosalind Franklin University in Illinois.
The FDA doesn’t have to follow the committee’s recommendation, but almost certainly will, though regulators said they may still make some changes.
“We are not bound at FDA by your vote, we can tweak this,” said Peter Marks, MD, director of the Center for Biologics Evaluation and Research at the FDA. Dr. Marks participated in the meeting and helped to draft the revised proposal.
If the FDA issues the recommended EUA, a council of independent advisors to the CDC will make specific recommendations about how the third doses should be given. After the CDC director weighs in, boosters will begin rolling out to the public.
Moderna submitted data to the FDA on Sept. 1 in support of adding a booster dose to its regimen. The agency has not yet scheduled a public review of that data.
The Biden administration is prepared to administer shots as soon as they get the green light, Surgeon General Vivek Murthy, MD, said at a White House briefing earlier Sept. 17.
"This process is consistent with what we outlined in August where our goals were to stay ahead of the virus," Dr. Murthy said. "Our goal then and now is to protect the health and well-being of the public. As soon as the FDA and CDC complete their evaluations, we will be ready to move forward accordingly."
He added, "We've used this time since our August announcement to communicate and coordinate with pharmacy partners, nursing homes, states, and localities."
White House COVID-19 Response Coordinator Jeff Zients said vaccine supply is "in good shape for all Americans to get boosters as recommended."
Taking cues from Israel
In considering Pfizer’s original request, the committee overwhelmingly felt that they didn’t have enough information to say that the benefits of an additional dose of vaccine in 16- and 17-year-olds would outweigh its risk. Teens have the highest risk of rare heart inflammation after vaccination, a side effect known as myocarditis. It is not known how the vaccines are causing these cases of heart swelling. Most who have been diagnosed with the condition have recovered, though some have needed hospital care.
Pfizer didn’t include 16- and 17-year-olds in its studies of boosters, which included about 300 people between the ages of 18 and 55. The company acknowledged that gap in its data but pointed to FDA guidance that said evidence from adults could be extrapolated to teens.
“We don’t know that much about risks,” said committee member Eric Rubin, MD, who is editor-in-chief of the New England Journal of Medicine.
Much of the data on the potential benefits and harms of third Pfizer doses comes from Israel, which first began rolling out boosters to older adults in July.
In a highly anticipated presentation, Sharon Alroy-Preis, Israel’s director of public health services, joined the meeting to describe Israel’s experience with boosters.
Israel began to see a third surge of COVID-19 cases in December.
“This was after having two waves and two lockdowns,” Ms. Alroy-Preis said. By the third surge, she said, Israelis were tired.
“We decided on a lockdown, but the compliance of the public wasn’t as it was in the previous two waves,” she said.
Then the vaccine arrived. Israel started vaccinations as soon as the FDA approved it, and they quickly vaccinated a high percentage of their population, about 3 months faster than the rest of the world.
All vaccinations are reported and tracked by the Ministry of Health, so the country is able to keep close tabs on how well the shots are working.
As vaccines rolled out, cases fell dramatically. The pandemic seemed to be behind them. Delta arrived in March. By June, their cases were doubling every 10 days, despite about 80% of their most vulnerable adults being fully vaccinated, she said.
Most concerning was that about 60% of severe cases were breakthrough cases in fully vaccinated individuals.
“We had to stop and figure out, was this a Delta issue,” she said. “Or was this a waning immunity issue.”
“We had some clue that it might not be the Delta variant, at least not alone,” she said.
People who had originally been first in line for the vaccines, seniors and health care workers, were having the highest rates of breakthrough infections. People further away from their second dose were more likely to get a breakthrough infection.
Ms. Alroy-Preis said that if they had not started booster doses in July, their hospitals would have been overwhelmed. They had projected that they would have 2,000 cases in the hospital each day.
Boosters have helped to flatten the curve, though they are still seeing a significant number of infections.
Data from Israel presented at the meeting show boosters are largely safe and effective at reducing severe outcomes in seniors. Israeli experience also showed that third doses, which generate very high levels of neutralizing antibodies—the first and fastest line of the body’s immune defense - -may also slow transmission of the virus.
Key differences in the U.S.
The benefit of slowing down the explosive spread of a highly contagious virus was tantalizing, but many members noted that circumstances in Israel are very different than in the United States. Israel went into its current Delta surge already having high levels of vaccination in its population. They also relied on the Pfizer vaccine almost exclusively for their campaign.
The United States used a different mix of vaccines – Pfizer, Moderna, and Johnson & Johnson -- and doesn’t have the same high level of vaccination coverage of its population.
In the United States, transmission is mainly being driven by unvaccinated people, Dr. Rubin noted.
“That really means the primary benefit is going to be in reducing disease,” he said, “And we know the people who are going to benefit from that … and those are the kinds of people the FDA has already approved a third dose for,” he said, referring to those with underlying health conditions.
But Israel only began vaccinating younger people a few weeks ago. Most are still within a window where rare risks like myocarditis could appear, Rubin noted.
He and other members of the committee said they wished they had more information about the safety of third doses in younger adults.
“We don’t have that right now, and I don’t think I would be comfortable giving it to a 16-year-old,” he said.
At the same time, the primary benefit for third doses would be in preventing severe disease, and overall, data from the United States and other countries show that two doses of the vaccines remain highly effective at preventing hospitalization and death.
Asked why Israel began to see more severe cases in fully vaccinated people, the CDC’s Sara Oliver, MD, a disease detective with the CDC, said it was probably due to a mix of factors including the fact that Israel defines severe cases a little differently.
In the United States, a severe case is generally a person who has to be hospitalized or who has died from the infection. In Israel, a person with a severe case is someone who has an elevated respiratory rate and someone who has a blood oxygen level less than 94%. In the United States, that kind of patient wouldn’t necessarily be hospitalized.
In the end, one of the two committee members who wanted full approval for Pfizer’s third doses said he was satisfied with the outcome.
Mark Sawyer, MD, a professor of pediatrics and infectious disease at the University of California at San Diego, said he voted yes on the first question because he thought full approval was the best way to give doctors the flexibility to prescribe the shots to vulnerable individuals.
“I’m really glad we authorized a vaccine for a third dose, and I plan to go out and get my vaccine this afternoon,” Dr. Sawyer said, noting that he was at high risk as a health care provider.
This article was updated 9/19/21.
A version of this article first appeared on Medscape.com.