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Possible obesity effect detected in cancer death rates
“By integrating 20 years of cancer mortality data, we demonstrated that trends in obesity-associated cancer mortality showed signs of recent deceleration, consistent with recent findings for heart disease mortality,” Christy L. Avery, PhD, and associates wrote in JAMA Network Open.
Improvements in mortality related to heart disease slowed after 2011, a phenomenon that has been associated with rising obesity rates. The age-adjusted mortality rate (AAMR) declined at an average of 3.8 deaths per 100,000 persons from 1999 to 2011 but only 0.7 deaths per 100,000 from 2011 to 2018, based on data from the Centers for Disease Control and Prevention’s Wide-Ranging Online Data for Epidemiologic Research (WONDER).
To understand trends in cancer mortality and their possible connection with obesity, data for 1999-2018 from the WONDER database were divided into obesity-associated and non–obesity-associated categories and compared with heart disease mortality, they explained. The database included more than 50 million deaths that matched inclusion criteria.
The analysis showed there was difference between obesity-associated and non–obesity-associated cancers that was obscured when all cancer deaths were considered together. The average annual change in AAMR for obesity-associated cancers slowed from –1.19 deaths per 100,000 in 1999-2011 to –0.83 in 2011-2018, Dr. Avery and associates reported.
For non–obesity-associated cancers, the annual change in AAMR increased from –1.62 per 100,000 for 1999-2011 to –2.29 for 2011-2018, following the trend for all cancers: –1.48 per 100,000 during 1999-2011 and –1.77 in 2011-2018, they said.
“The largest mortality decreases were observed for melanoma of the skin and lung cancer, two cancers not associated with obesity. For obesity-associated cancers, stable or increasing mortality rates have been observed for liver and pancreatic cancer among both men and women as well as for uterine cancer among women,” the investigators wrote.
Demographically, however, the slowing improvement in mortality for obesity-associated cancers did not follow the trend for heart disease. The deceleration for cancer was more pronounced for women and for non-Hispanic Whites and not seen at all in non-Hispanic Asian/Pacific Islander individuals. “For heart disease, evidence of a deceleration was consistent across sex, race, and ethnicity,” they said.
There are “longstanding disparities in obesity” among various populations in the United States, and the recent trend of obesity occurring earlier in life may be having an effect. “Whether the findings of decelerating mortality rates potentially signal a changing profile of cancer and heart disease mortality as the consequences of the obesity epidemic are realized remains to be seen,” they concluded.
The investigators reported receiving grants from the National Institutes of Health during the conduct of the study, but no other disclosures were reported.
“By integrating 20 years of cancer mortality data, we demonstrated that trends in obesity-associated cancer mortality showed signs of recent deceleration, consistent with recent findings for heart disease mortality,” Christy L. Avery, PhD, and associates wrote in JAMA Network Open.
Improvements in mortality related to heart disease slowed after 2011, a phenomenon that has been associated with rising obesity rates. The age-adjusted mortality rate (AAMR) declined at an average of 3.8 deaths per 100,000 persons from 1999 to 2011 but only 0.7 deaths per 100,000 from 2011 to 2018, based on data from the Centers for Disease Control and Prevention’s Wide-Ranging Online Data for Epidemiologic Research (WONDER).
To understand trends in cancer mortality and their possible connection with obesity, data for 1999-2018 from the WONDER database were divided into obesity-associated and non–obesity-associated categories and compared with heart disease mortality, they explained. The database included more than 50 million deaths that matched inclusion criteria.
The analysis showed there was difference between obesity-associated and non–obesity-associated cancers that was obscured when all cancer deaths were considered together. The average annual change in AAMR for obesity-associated cancers slowed from –1.19 deaths per 100,000 in 1999-2011 to –0.83 in 2011-2018, Dr. Avery and associates reported.
For non–obesity-associated cancers, the annual change in AAMR increased from –1.62 per 100,000 for 1999-2011 to –2.29 for 2011-2018, following the trend for all cancers: –1.48 per 100,000 during 1999-2011 and –1.77 in 2011-2018, they said.
“The largest mortality decreases were observed for melanoma of the skin and lung cancer, two cancers not associated with obesity. For obesity-associated cancers, stable or increasing mortality rates have been observed for liver and pancreatic cancer among both men and women as well as for uterine cancer among women,” the investigators wrote.
Demographically, however, the slowing improvement in mortality for obesity-associated cancers did not follow the trend for heart disease. The deceleration for cancer was more pronounced for women and for non-Hispanic Whites and not seen at all in non-Hispanic Asian/Pacific Islander individuals. “For heart disease, evidence of a deceleration was consistent across sex, race, and ethnicity,” they said.
There are “longstanding disparities in obesity” among various populations in the United States, and the recent trend of obesity occurring earlier in life may be having an effect. “Whether the findings of decelerating mortality rates potentially signal a changing profile of cancer and heart disease mortality as the consequences of the obesity epidemic are realized remains to be seen,” they concluded.
The investigators reported receiving grants from the National Institutes of Health during the conduct of the study, but no other disclosures were reported.
“By integrating 20 years of cancer mortality data, we demonstrated that trends in obesity-associated cancer mortality showed signs of recent deceleration, consistent with recent findings for heart disease mortality,” Christy L. Avery, PhD, and associates wrote in JAMA Network Open.
Improvements in mortality related to heart disease slowed after 2011, a phenomenon that has been associated with rising obesity rates. The age-adjusted mortality rate (AAMR) declined at an average of 3.8 deaths per 100,000 persons from 1999 to 2011 but only 0.7 deaths per 100,000 from 2011 to 2018, based on data from the Centers for Disease Control and Prevention’s Wide-Ranging Online Data for Epidemiologic Research (WONDER).
To understand trends in cancer mortality and their possible connection with obesity, data for 1999-2018 from the WONDER database were divided into obesity-associated and non–obesity-associated categories and compared with heart disease mortality, they explained. The database included more than 50 million deaths that matched inclusion criteria.
The analysis showed there was difference between obesity-associated and non–obesity-associated cancers that was obscured when all cancer deaths were considered together. The average annual change in AAMR for obesity-associated cancers slowed from –1.19 deaths per 100,000 in 1999-2011 to –0.83 in 2011-2018, Dr. Avery and associates reported.
For non–obesity-associated cancers, the annual change in AAMR increased from –1.62 per 100,000 for 1999-2011 to –2.29 for 2011-2018, following the trend for all cancers: –1.48 per 100,000 during 1999-2011 and –1.77 in 2011-2018, they said.
“The largest mortality decreases were observed for melanoma of the skin and lung cancer, two cancers not associated with obesity. For obesity-associated cancers, stable or increasing mortality rates have been observed for liver and pancreatic cancer among both men and women as well as for uterine cancer among women,” the investigators wrote.
Demographically, however, the slowing improvement in mortality for obesity-associated cancers did not follow the trend for heart disease. The deceleration for cancer was more pronounced for women and for non-Hispanic Whites and not seen at all in non-Hispanic Asian/Pacific Islander individuals. “For heart disease, evidence of a deceleration was consistent across sex, race, and ethnicity,” they said.
There are “longstanding disparities in obesity” among various populations in the United States, and the recent trend of obesity occurring earlier in life may be having an effect. “Whether the findings of decelerating mortality rates potentially signal a changing profile of cancer and heart disease mortality as the consequences of the obesity epidemic are realized remains to be seen,” they concluded.
The investigators reported receiving grants from the National Institutes of Health during the conduct of the study, but no other disclosures were reported.
FROM JAMA NETWORK OPEN
A simple new definition for ‘metabolically healthy obesity’?
Scientists have proposed a simple new definition for “metabolically healthy obesity” to identify individuals who do not have an increased risk of cardiovascular disease (CVD) death and total mortality.
The team – led by Anika Zembic, MPH, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany – performed an assessment of anthropometric and metabolic risk factors as well as mortality data from two cohorts that “yielded a simple definition to categorize participants with obesity as metabolically healthy or unhealthy.”
They defined “metabolically healthy” as systolic blood pressure <130 mm Hg and no use of blood pressure-lowering medication; waist-to-hip ratio <0.95 (in women) and <1.03 (in men); and no prevalent type 2 diabetes.
Based on this new definition, 42% of participants in the third U.S. National Health and Nutrition Examination Survey (NHANES-III) and 19% of participants in the UK Biobank study had metabolically healthy obesity and did not have an increased risk for CVD mortality and total mortality compared with individuals with metabolically healthy normal weight.
“People with a phenotype defined as metabolically unhealthy using this definition had significantly higher hazard ratios for [CVD] mortality and total mortality irrespective of body mass index category, and people with phenotypes defined as having metabolically healthy obesity displayed no increased risk,” the researchers noted in their article, published May 7 in JAMA Network Open.
“Our new definition may be important not only to stratify risk of mortality in people with obesity, but also in people with overweight and normal weight,” they concluded.
Thirty different definitions of ‘metabolically healthy obesity’
“To date, there is no universally accepted standard for defining [metabolically healthy obesity] and more than 30 different definitions have been used to operationalize the phenotypes in studies,” which may explain the “continued unresolved debate” about outcomes in patients with metabolically unhealthy obesity, Ayana K. April-Sanders, PhD, and Carlos J. Rodriguez, MD, MPH, from Albert Einstein College of Medicine, New York, wrote in an accompanying commentary.
The current study, they noted, suggests that waist-to-hip ratio is a better measure of central adiposity than waist circumference, and that the effect of dyslipidemia on CVD mortality may be weaker among individuals with obesity.
However, the findings may not be generalizable to other CVD outcomes, they cautioned.
And importantly, some individuals with metabolically healthy obesity will likely transition to unhealthy obesity over time due to weight gain, aging, and lack of physical activity.
Therefore, “the present study provides a prototype of how that definition can be derived, but more rigorous tests and evidence using similar techniques are needed, particularly in prospective studies,” according to Dr. April-Sanders and Dr. Rodriguez.
They call for more research to establish a standardized definition of metabolically healthy obesity and then, using that definition, to determine the prevalence of healthy and unhealthy obesity and identify factors that preserve healthy obesity.
Definition developed from NHANES cohort, validated in UK biobank
Ms. Zembic and colleagues explained that previous definitions for metabolically healthy obesity were mainly based on the absence of either metabolic syndrome or insulin resistance, but some individuals with obesity but without metabolic disease still have increased risks of CVD mortality and total mortality.
To develop a more precise definition of metabolically healthy obesity, the researchers analyzed data from 12,341 individuals in the United States who participated in NHANES-III, conducted between 1988 and 1994. The individuals were a mean age of 42 and 51% were women, and they were followed for an average of 14.5 years.
The researchers validated this definition using data from 374,079 individuals in the population-based UK Biobank cohort who were assessed in 2006 to 2010. Those individuals were a mean age of 56 and 55% were women, and they were followed for a mean of 7.8 years.
The combination of systolic blood pressure and waist-to-hip ratio had the strongest association with CVD mortality and total mortality, and the prevalence of type 2 diabetes was also associated with greater risk.
Regardless of BMI, all groups of metabolically unhealthy individuals had increased risks of CVD mortality and total mortality.
The study and some of the researchers were supported by grants from the German Federal Ministry of Education and Research.
A version of this article first appeared on Medscape.com.
Scientists have proposed a simple new definition for “metabolically healthy obesity” to identify individuals who do not have an increased risk of cardiovascular disease (CVD) death and total mortality.
The team – led by Anika Zembic, MPH, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany – performed an assessment of anthropometric and metabolic risk factors as well as mortality data from two cohorts that “yielded a simple definition to categorize participants with obesity as metabolically healthy or unhealthy.”
They defined “metabolically healthy” as systolic blood pressure <130 mm Hg and no use of blood pressure-lowering medication; waist-to-hip ratio <0.95 (in women) and <1.03 (in men); and no prevalent type 2 diabetes.
Based on this new definition, 42% of participants in the third U.S. National Health and Nutrition Examination Survey (NHANES-III) and 19% of participants in the UK Biobank study had metabolically healthy obesity and did not have an increased risk for CVD mortality and total mortality compared with individuals with metabolically healthy normal weight.
“People with a phenotype defined as metabolically unhealthy using this definition had significantly higher hazard ratios for [CVD] mortality and total mortality irrespective of body mass index category, and people with phenotypes defined as having metabolically healthy obesity displayed no increased risk,” the researchers noted in their article, published May 7 in JAMA Network Open.
“Our new definition may be important not only to stratify risk of mortality in people with obesity, but also in people with overweight and normal weight,” they concluded.
Thirty different definitions of ‘metabolically healthy obesity’
“To date, there is no universally accepted standard for defining [metabolically healthy obesity] and more than 30 different definitions have been used to operationalize the phenotypes in studies,” which may explain the “continued unresolved debate” about outcomes in patients with metabolically unhealthy obesity, Ayana K. April-Sanders, PhD, and Carlos J. Rodriguez, MD, MPH, from Albert Einstein College of Medicine, New York, wrote in an accompanying commentary.
The current study, they noted, suggests that waist-to-hip ratio is a better measure of central adiposity than waist circumference, and that the effect of dyslipidemia on CVD mortality may be weaker among individuals with obesity.
However, the findings may not be generalizable to other CVD outcomes, they cautioned.
And importantly, some individuals with metabolically healthy obesity will likely transition to unhealthy obesity over time due to weight gain, aging, and lack of physical activity.
Therefore, “the present study provides a prototype of how that definition can be derived, but more rigorous tests and evidence using similar techniques are needed, particularly in prospective studies,” according to Dr. April-Sanders and Dr. Rodriguez.
They call for more research to establish a standardized definition of metabolically healthy obesity and then, using that definition, to determine the prevalence of healthy and unhealthy obesity and identify factors that preserve healthy obesity.
Definition developed from NHANES cohort, validated in UK biobank
Ms. Zembic and colleagues explained that previous definitions for metabolically healthy obesity were mainly based on the absence of either metabolic syndrome or insulin resistance, but some individuals with obesity but without metabolic disease still have increased risks of CVD mortality and total mortality.
To develop a more precise definition of metabolically healthy obesity, the researchers analyzed data from 12,341 individuals in the United States who participated in NHANES-III, conducted between 1988 and 1994. The individuals were a mean age of 42 and 51% were women, and they were followed for an average of 14.5 years.
The researchers validated this definition using data from 374,079 individuals in the population-based UK Biobank cohort who were assessed in 2006 to 2010. Those individuals were a mean age of 56 and 55% were women, and they were followed for a mean of 7.8 years.
The combination of systolic blood pressure and waist-to-hip ratio had the strongest association with CVD mortality and total mortality, and the prevalence of type 2 diabetes was also associated with greater risk.
Regardless of BMI, all groups of metabolically unhealthy individuals had increased risks of CVD mortality and total mortality.
The study and some of the researchers were supported by grants from the German Federal Ministry of Education and Research.
A version of this article first appeared on Medscape.com.
Scientists have proposed a simple new definition for “metabolically healthy obesity” to identify individuals who do not have an increased risk of cardiovascular disease (CVD) death and total mortality.
The team – led by Anika Zembic, MPH, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany – performed an assessment of anthropometric and metabolic risk factors as well as mortality data from two cohorts that “yielded a simple definition to categorize participants with obesity as metabolically healthy or unhealthy.”
They defined “metabolically healthy” as systolic blood pressure <130 mm Hg and no use of blood pressure-lowering medication; waist-to-hip ratio <0.95 (in women) and <1.03 (in men); and no prevalent type 2 diabetes.
Based on this new definition, 42% of participants in the third U.S. National Health and Nutrition Examination Survey (NHANES-III) and 19% of participants in the UK Biobank study had metabolically healthy obesity and did not have an increased risk for CVD mortality and total mortality compared with individuals with metabolically healthy normal weight.
“People with a phenotype defined as metabolically unhealthy using this definition had significantly higher hazard ratios for [CVD] mortality and total mortality irrespective of body mass index category, and people with phenotypes defined as having metabolically healthy obesity displayed no increased risk,” the researchers noted in their article, published May 7 in JAMA Network Open.
“Our new definition may be important not only to stratify risk of mortality in people with obesity, but also in people with overweight and normal weight,” they concluded.
Thirty different definitions of ‘metabolically healthy obesity’
“To date, there is no universally accepted standard for defining [metabolically healthy obesity] and more than 30 different definitions have been used to operationalize the phenotypes in studies,” which may explain the “continued unresolved debate” about outcomes in patients with metabolically unhealthy obesity, Ayana K. April-Sanders, PhD, and Carlos J. Rodriguez, MD, MPH, from Albert Einstein College of Medicine, New York, wrote in an accompanying commentary.
The current study, they noted, suggests that waist-to-hip ratio is a better measure of central adiposity than waist circumference, and that the effect of dyslipidemia on CVD mortality may be weaker among individuals with obesity.
However, the findings may not be generalizable to other CVD outcomes, they cautioned.
And importantly, some individuals with metabolically healthy obesity will likely transition to unhealthy obesity over time due to weight gain, aging, and lack of physical activity.
Therefore, “the present study provides a prototype of how that definition can be derived, but more rigorous tests and evidence using similar techniques are needed, particularly in prospective studies,” according to Dr. April-Sanders and Dr. Rodriguez.
They call for more research to establish a standardized definition of metabolically healthy obesity and then, using that definition, to determine the prevalence of healthy and unhealthy obesity and identify factors that preserve healthy obesity.
Definition developed from NHANES cohort, validated in UK biobank
Ms. Zembic and colleagues explained that previous definitions for metabolically healthy obesity were mainly based on the absence of either metabolic syndrome or insulin resistance, but some individuals with obesity but without metabolic disease still have increased risks of CVD mortality and total mortality.
To develop a more precise definition of metabolically healthy obesity, the researchers analyzed data from 12,341 individuals in the United States who participated in NHANES-III, conducted between 1988 and 1994. The individuals were a mean age of 42 and 51% were women, and they were followed for an average of 14.5 years.
The researchers validated this definition using data from 374,079 individuals in the population-based UK Biobank cohort who were assessed in 2006 to 2010. Those individuals were a mean age of 56 and 55% were women, and they were followed for a mean of 7.8 years.
The combination of systolic blood pressure and waist-to-hip ratio had the strongest association with CVD mortality and total mortality, and the prevalence of type 2 diabetes was also associated with greater risk.
Regardless of BMI, all groups of metabolically unhealthy individuals had increased risks of CVD mortality and total mortality.
The study and some of the researchers were supported by grants from the German Federal Ministry of Education and Research.
A version of this article first appeared on Medscape.com.
Dr. Topol talks: COVID-19 variants are innocent until proven guilty
Editor in Chief of this news organization Eric Topol, MD, founder and director of the Scripps Research Translational Institute in La Jolla, Calif., and professor of molecular medicine, has been closely following COVID-19 data since the pandemic began. He spoke with writer Miriam E. Tucker about the latest on SARS-CoV-2 variants and their impact on vaccine efficacy. The conversation serves as a follow-up to his April 13, 2021, New York Times opinion piece, in which he advised readers that “all variants are innocent until proven guilty.”
You have expressed overall confidence in the efficacy of the vaccines thus far despite the emergence of variants, with some caveats. How do you see the current situation?
The Centers for Disease Control and Prevention has designated five “variants of concern,” but only three of them are real concerns – B.1.1.7, first detected in the United Kingdom; P.1, in Brazil and Japan; and B.1.351, in South Africa. Yet, all three are susceptible to our current vaccines.
The U.K. B.1.1.7 is the worst variant of all because it’s hypertransmissible, so I call it a “superspreader strain.” It also causes more severe illness independent of the spread, so it’s a double whammy. It’s clear that it also causes more deaths. The only arguable point is whether it’s 30% or 50% more deaths, but regardless, it’s more lethal and more transmissible.
The B.1.1.7 is going to be the dominant strain worldwide. It could develop new mutations within it that could come back to haunt us. We must keep watch.
But for now, it’s fully responsive to all the vaccines, which is great because if we didn’t have them, we wouldn’t have gotten through this U.S. pandemic like we have, and neither would Israel and the United Kingdom and other countries that have been able to get out of the crisis. We met the enemy and put it in check.
As for the South Africa variant of concern, B.1.351, we just got some encouraging news showing that it›s very responsive to the Pfizer/BioNTech mRNA vaccine in large numbers of people. The study was conducted in Qatar following that country’s mass immunization campaign in which a total of 385,853 people had received at least one vaccine dose and 265,410 had completed the two doses as of March 31, 2021.
At 2 weeks past the second dose, the vaccine was 75% effective at preventing any documented infection with the B.1.351 variant and 89.5% effective against B.1.1.7. The vaccine’s effectiveness against severe, critical, or fatal COVID-19 was greater than 97.4% for all circulating strains in Qatar, where B.1.1.7 and B.1.351 are most prominent.
We also know that B.1.351 is very responsive to the Johnson & Johnson vaccine and the Novavax [vaccine in development] to a lesser degree. It is the most immune-evading variant we’ve seen thus far, with the highest likelihood of providing some vaccine resistance, yet not enough to interfere with vaccination campaigns. So that’s great news.
The caveats here are that you definitely need two doses of the mRNA vaccines to combat the B.1.351 variant. Also, the AstraZeneca vaccine failed to prevent it in South Africa. However, that study was hard to judge because it was underpowered for number of people with mild infections. So, it didn’t look as if it had any efficacy, but maybe it would if tested in a real trial.
The P.1 (Brazil) variant is the second-highest concern after B.1.1.7 because it’s the only one in the United States that’s still headed up. It seems to be competing a bit with B.1.1.7 here. We know it was associated with the crisis in Brazil, in Chile, and some other South American countries. It has some immune escape, but not as bad as B.1.351. It also appears to have somewhat greater transmissibility but not as much as B.1.1.7.
With P.1, we just don’t know enough yet. It was difficult to assess in Brazil because they were in the midst of a catastrophe – like India is now – and you don’t know how much of it is dragged by the catastrophe vs driving it.
We have to respond to P.1 carefully. There are some good data that it does respond to the Chinese vaccine Sinovac and the AstraZeneca vaccine, and it appears to respond to the others as well, based on serum studies. So it doesn’t look like vaccines will be the worry with this variant. Rather, it could be competing with B.1.1.7 and could lead to breakthrough infections in vaccinated people or reinfections in unvaccinated people who had COVID-19. We need several more weeks to sort it out.
Although the B.1.427 and B.1.429 variants initially seen in California remain on the CDC’s concern list, I’m not worried about them.
You mentioned the current COVID-19 crisis in India, where a new variant has been described as a “double mutant,” but on Twitter you called it a “scariant.” Why?
First of all, the B.1.617 variant isn’t a double mutant. It has 15 mutations. It’s a stupid term, focusing on two mutations which largely have been put aside as to concern. One of them is the L452R, which is the same as one of the California variants, and that hasn’t proved to be particularly serious or concerning. The other is the 484Q, and it’s not clear whether that has any function.
The B.1.617 is not the driver of the catastrophe in India. It may be contributing a small amount, but it has been overhyped as the double mutant that’s causing it all. Adding to that are what I call “scariant” headlines here in the United States when a few cases of that variant have been seen.
I coined the term scariant in early February because it was a pretty clear trend. People don’t know what variants are. They know a little bit about mutations but not variants, and they’re scared. A few variants are concerning, but we keep learning more and more things to decrease the concern. That’s why I wrote the New York Times op-ed, to try to provide some reassurance, since there’s such paranoia.
Do you think booster vaccinations will be necessary? If so, will those be of the original vaccines or new ones that incorporate the variants?
As we go forward, there’s still potential for new variants that we haven’t seen yet that combine the worst of all features – transmissibility and immune evasion – especially since we have a world where COVID-19 is unchecked. So, we’re not out of it yet, but at least for the moment, we have vaccines that are capable of protecting against all variants.
In most people, the immune response against SARS-CoV-2 is very durable and strong and may well last for years. With the most closely related SARS-CoV-1, people still had immune responses up to 18 years later. However, some people will have less robust vaccine responses, including the elderly and the immunocompromised. If they don’t have great responses to the vaccine to start with, over time they’re likely to become more vulnerable, especially if they’re exposed to the variants with some degree of immune evasion.
I think we need to study these individuals post vaccination. A lot of people fit into those categories, including seniors, people being treated for cancer or autoimmune conditions, or post organ transplant. We could set up a prospective study to see whether they develop symptomatic COVID-19 and if so, from what – the original strain, B.1.1.7, or the newer variants.
That’s where I think booster shots may be needed. They may not be necessary across the board, but perhaps just in these special subgroups.
All of the current vaccines can be tweaked to include new variants, but the need for that is uncertain as of now. Moderna is working on a so-called bivalent vaccine that includes the original SARS-CoV-2 strain plus the B.1.351 variant, but it isn’t clear that that’s going to be necessary.
Currently, at least 200 COVID-19 vaccines are in development. There will be vaccines you can inhale, room temperature mRNA vaccines, and potentially even oral vaccines.
In the near future, Novavax is close, and there will likely be a two-dose Johnson & Johnson version that has the same potency as the mRNA vaccines. There are a lot of moving parts here.
There may be a step down in efficacy from mRNA to the others, though, and that shouldn’t be discounted. All of the available vaccines so far protect very well against severe disease and death, but some are less effective against mild to moderate infections, which may then lead to long COVID. We don’t yet know whether those who get mild infection post vaccination can still get long COVID.
What do you think it will take to achieve herd immunity?
I prefer the term “containment.” It’s quantitative. If you get to an infection rate of less than 1 in 100,000 people, as they’ve done in Israel, with 0.8 per 100,000, then you have the virus in check, and there will be very little spread when it’s at that controlled rate, with no outbreaks. The United States is currently at about 15 per 100,000. California is at 4. That still has to get lower.
It will be a challenge to get to President Biden’s goal of having 70% of U.S. adults given at least one dose by July 4. We’re now at about 57%. To get that next 13% of adults is going to take an all-out effort: mobile units, going to homes, making it ultraconvenient, education for people with safety concerns, incentivization, and days off.
We also need to get employers, universities, and health systems to get to the mandatory level. We haven’t done that yet. Some universities have mandated it for students, faculty, and staff. We need it in more health care systems. Right now, we only have a couple. We mandate flu shots, and flu is nothing, compared with COVID-19. And the COVID-19 vaccine is far more efficacious – flu shots are 40% efficacious, while these are 95%. COVID-19 is a tenfold more lethal and serious disease, and much more spreadable.
People are using the lack of full licensure by the Food and Drug Administration – as opposed to emergency use authorization – as an excuse not to get vaccinated. A biologics license application takes time to approve. Meanwhile, we have hundreds of millions of doses that have been well tolerated and incredibly effective.
Another aspect to consider regarding containment is that about 110 million Americans have already had COVID-19, even though only about 30 million cases have been confirmed. Most of these people have immune protection, although it’s not as good as if they have one vaccine dose. But they have enough protection to be part of the story here of the wall against COVID-19 and will help us get through this.
That’s a silver lining of having an unchecked epidemic for the entire year of 2020. The good part is that’s helping to get us to achieve an incredible level of containment when we haven’t even been close. Right now, we’re as good as the country has been in the pandemic, but we still have a long gap to get down to that 1 per 100,000. That’s what we should be working toward, and we can get there.
A version of this article first appeared on Medscape.com.
Editor in Chief of this news organization Eric Topol, MD, founder and director of the Scripps Research Translational Institute in La Jolla, Calif., and professor of molecular medicine, has been closely following COVID-19 data since the pandemic began. He spoke with writer Miriam E. Tucker about the latest on SARS-CoV-2 variants and their impact on vaccine efficacy. The conversation serves as a follow-up to his April 13, 2021, New York Times opinion piece, in which he advised readers that “all variants are innocent until proven guilty.”
You have expressed overall confidence in the efficacy of the vaccines thus far despite the emergence of variants, with some caveats. How do you see the current situation?
The Centers for Disease Control and Prevention has designated five “variants of concern,” but only three of them are real concerns – B.1.1.7, first detected in the United Kingdom; P.1, in Brazil and Japan; and B.1.351, in South Africa. Yet, all three are susceptible to our current vaccines.
The U.K. B.1.1.7 is the worst variant of all because it’s hypertransmissible, so I call it a “superspreader strain.” It also causes more severe illness independent of the spread, so it’s a double whammy. It’s clear that it also causes more deaths. The only arguable point is whether it’s 30% or 50% more deaths, but regardless, it’s more lethal and more transmissible.
The B.1.1.7 is going to be the dominant strain worldwide. It could develop new mutations within it that could come back to haunt us. We must keep watch.
But for now, it’s fully responsive to all the vaccines, which is great because if we didn’t have them, we wouldn’t have gotten through this U.S. pandemic like we have, and neither would Israel and the United Kingdom and other countries that have been able to get out of the crisis. We met the enemy and put it in check.
As for the South Africa variant of concern, B.1.351, we just got some encouraging news showing that it›s very responsive to the Pfizer/BioNTech mRNA vaccine in large numbers of people. The study was conducted in Qatar following that country’s mass immunization campaign in which a total of 385,853 people had received at least one vaccine dose and 265,410 had completed the two doses as of March 31, 2021.
At 2 weeks past the second dose, the vaccine was 75% effective at preventing any documented infection with the B.1.351 variant and 89.5% effective against B.1.1.7. The vaccine’s effectiveness against severe, critical, or fatal COVID-19 was greater than 97.4% for all circulating strains in Qatar, where B.1.1.7 and B.1.351 are most prominent.
We also know that B.1.351 is very responsive to the Johnson & Johnson vaccine and the Novavax [vaccine in development] to a lesser degree. It is the most immune-evading variant we’ve seen thus far, with the highest likelihood of providing some vaccine resistance, yet not enough to interfere with vaccination campaigns. So that’s great news.
The caveats here are that you definitely need two doses of the mRNA vaccines to combat the B.1.351 variant. Also, the AstraZeneca vaccine failed to prevent it in South Africa. However, that study was hard to judge because it was underpowered for number of people with mild infections. So, it didn’t look as if it had any efficacy, but maybe it would if tested in a real trial.
The P.1 (Brazil) variant is the second-highest concern after B.1.1.7 because it’s the only one in the United States that’s still headed up. It seems to be competing a bit with B.1.1.7 here. We know it was associated with the crisis in Brazil, in Chile, and some other South American countries. It has some immune escape, but not as bad as B.1.351. It also appears to have somewhat greater transmissibility but not as much as B.1.1.7.
With P.1, we just don’t know enough yet. It was difficult to assess in Brazil because they were in the midst of a catastrophe – like India is now – and you don’t know how much of it is dragged by the catastrophe vs driving it.
We have to respond to P.1 carefully. There are some good data that it does respond to the Chinese vaccine Sinovac and the AstraZeneca vaccine, and it appears to respond to the others as well, based on serum studies. So it doesn’t look like vaccines will be the worry with this variant. Rather, it could be competing with B.1.1.7 and could lead to breakthrough infections in vaccinated people or reinfections in unvaccinated people who had COVID-19. We need several more weeks to sort it out.
Although the B.1.427 and B.1.429 variants initially seen in California remain on the CDC’s concern list, I’m not worried about them.
You mentioned the current COVID-19 crisis in India, where a new variant has been described as a “double mutant,” but on Twitter you called it a “scariant.” Why?
First of all, the B.1.617 variant isn’t a double mutant. It has 15 mutations. It’s a stupid term, focusing on two mutations which largely have been put aside as to concern. One of them is the L452R, which is the same as one of the California variants, and that hasn’t proved to be particularly serious or concerning. The other is the 484Q, and it’s not clear whether that has any function.
The B.1.617 is not the driver of the catastrophe in India. It may be contributing a small amount, but it has been overhyped as the double mutant that’s causing it all. Adding to that are what I call “scariant” headlines here in the United States when a few cases of that variant have been seen.
I coined the term scariant in early February because it was a pretty clear trend. People don’t know what variants are. They know a little bit about mutations but not variants, and they’re scared. A few variants are concerning, but we keep learning more and more things to decrease the concern. That’s why I wrote the New York Times op-ed, to try to provide some reassurance, since there’s such paranoia.
Do you think booster vaccinations will be necessary? If so, will those be of the original vaccines or new ones that incorporate the variants?
As we go forward, there’s still potential for new variants that we haven’t seen yet that combine the worst of all features – transmissibility and immune evasion – especially since we have a world where COVID-19 is unchecked. So, we’re not out of it yet, but at least for the moment, we have vaccines that are capable of protecting against all variants.
In most people, the immune response against SARS-CoV-2 is very durable and strong and may well last for years. With the most closely related SARS-CoV-1, people still had immune responses up to 18 years later. However, some people will have less robust vaccine responses, including the elderly and the immunocompromised. If they don’t have great responses to the vaccine to start with, over time they’re likely to become more vulnerable, especially if they’re exposed to the variants with some degree of immune evasion.
I think we need to study these individuals post vaccination. A lot of people fit into those categories, including seniors, people being treated for cancer or autoimmune conditions, or post organ transplant. We could set up a prospective study to see whether they develop symptomatic COVID-19 and if so, from what – the original strain, B.1.1.7, or the newer variants.
That’s where I think booster shots may be needed. They may not be necessary across the board, but perhaps just in these special subgroups.
All of the current vaccines can be tweaked to include new variants, but the need for that is uncertain as of now. Moderna is working on a so-called bivalent vaccine that includes the original SARS-CoV-2 strain plus the B.1.351 variant, but it isn’t clear that that’s going to be necessary.
Currently, at least 200 COVID-19 vaccines are in development. There will be vaccines you can inhale, room temperature mRNA vaccines, and potentially even oral vaccines.
In the near future, Novavax is close, and there will likely be a two-dose Johnson & Johnson version that has the same potency as the mRNA vaccines. There are a lot of moving parts here.
There may be a step down in efficacy from mRNA to the others, though, and that shouldn’t be discounted. All of the available vaccines so far protect very well against severe disease and death, but some are less effective against mild to moderate infections, which may then lead to long COVID. We don’t yet know whether those who get mild infection post vaccination can still get long COVID.
What do you think it will take to achieve herd immunity?
I prefer the term “containment.” It’s quantitative. If you get to an infection rate of less than 1 in 100,000 people, as they’ve done in Israel, with 0.8 per 100,000, then you have the virus in check, and there will be very little spread when it’s at that controlled rate, with no outbreaks. The United States is currently at about 15 per 100,000. California is at 4. That still has to get lower.
It will be a challenge to get to President Biden’s goal of having 70% of U.S. adults given at least one dose by July 4. We’re now at about 57%. To get that next 13% of adults is going to take an all-out effort: mobile units, going to homes, making it ultraconvenient, education for people with safety concerns, incentivization, and days off.
We also need to get employers, universities, and health systems to get to the mandatory level. We haven’t done that yet. Some universities have mandated it for students, faculty, and staff. We need it in more health care systems. Right now, we only have a couple. We mandate flu shots, and flu is nothing, compared with COVID-19. And the COVID-19 vaccine is far more efficacious – flu shots are 40% efficacious, while these are 95%. COVID-19 is a tenfold more lethal and serious disease, and much more spreadable.
People are using the lack of full licensure by the Food and Drug Administration – as opposed to emergency use authorization – as an excuse not to get vaccinated. A biologics license application takes time to approve. Meanwhile, we have hundreds of millions of doses that have been well tolerated and incredibly effective.
Another aspect to consider regarding containment is that about 110 million Americans have already had COVID-19, even though only about 30 million cases have been confirmed. Most of these people have immune protection, although it’s not as good as if they have one vaccine dose. But they have enough protection to be part of the story here of the wall against COVID-19 and will help us get through this.
That’s a silver lining of having an unchecked epidemic for the entire year of 2020. The good part is that’s helping to get us to achieve an incredible level of containment when we haven’t even been close. Right now, we’re as good as the country has been in the pandemic, but we still have a long gap to get down to that 1 per 100,000. That’s what we should be working toward, and we can get there.
A version of this article first appeared on Medscape.com.
Editor in Chief of this news organization Eric Topol, MD, founder and director of the Scripps Research Translational Institute in La Jolla, Calif., and professor of molecular medicine, has been closely following COVID-19 data since the pandemic began. He spoke with writer Miriam E. Tucker about the latest on SARS-CoV-2 variants and their impact on vaccine efficacy. The conversation serves as a follow-up to his April 13, 2021, New York Times opinion piece, in which he advised readers that “all variants are innocent until proven guilty.”
You have expressed overall confidence in the efficacy of the vaccines thus far despite the emergence of variants, with some caveats. How do you see the current situation?
The Centers for Disease Control and Prevention has designated five “variants of concern,” but only three of them are real concerns – B.1.1.7, first detected in the United Kingdom; P.1, in Brazil and Japan; and B.1.351, in South Africa. Yet, all three are susceptible to our current vaccines.
The U.K. B.1.1.7 is the worst variant of all because it’s hypertransmissible, so I call it a “superspreader strain.” It also causes more severe illness independent of the spread, so it’s a double whammy. It’s clear that it also causes more deaths. The only arguable point is whether it’s 30% or 50% more deaths, but regardless, it’s more lethal and more transmissible.
The B.1.1.7 is going to be the dominant strain worldwide. It could develop new mutations within it that could come back to haunt us. We must keep watch.
But for now, it’s fully responsive to all the vaccines, which is great because if we didn’t have them, we wouldn’t have gotten through this U.S. pandemic like we have, and neither would Israel and the United Kingdom and other countries that have been able to get out of the crisis. We met the enemy and put it in check.
As for the South Africa variant of concern, B.1.351, we just got some encouraging news showing that it›s very responsive to the Pfizer/BioNTech mRNA vaccine in large numbers of people. The study was conducted in Qatar following that country’s mass immunization campaign in which a total of 385,853 people had received at least one vaccine dose and 265,410 had completed the two doses as of March 31, 2021.
At 2 weeks past the second dose, the vaccine was 75% effective at preventing any documented infection with the B.1.351 variant and 89.5% effective against B.1.1.7. The vaccine’s effectiveness against severe, critical, or fatal COVID-19 was greater than 97.4% for all circulating strains in Qatar, where B.1.1.7 and B.1.351 are most prominent.
We also know that B.1.351 is very responsive to the Johnson & Johnson vaccine and the Novavax [vaccine in development] to a lesser degree. It is the most immune-evading variant we’ve seen thus far, with the highest likelihood of providing some vaccine resistance, yet not enough to interfere with vaccination campaigns. So that’s great news.
The caveats here are that you definitely need two doses of the mRNA vaccines to combat the B.1.351 variant. Also, the AstraZeneca vaccine failed to prevent it in South Africa. However, that study was hard to judge because it was underpowered for number of people with mild infections. So, it didn’t look as if it had any efficacy, but maybe it would if tested in a real trial.
The P.1 (Brazil) variant is the second-highest concern after B.1.1.7 because it’s the only one in the United States that’s still headed up. It seems to be competing a bit with B.1.1.7 here. We know it was associated with the crisis in Brazil, in Chile, and some other South American countries. It has some immune escape, but not as bad as B.1.351. It also appears to have somewhat greater transmissibility but not as much as B.1.1.7.
With P.1, we just don’t know enough yet. It was difficult to assess in Brazil because they were in the midst of a catastrophe – like India is now – and you don’t know how much of it is dragged by the catastrophe vs driving it.
We have to respond to P.1 carefully. There are some good data that it does respond to the Chinese vaccine Sinovac and the AstraZeneca vaccine, and it appears to respond to the others as well, based on serum studies. So it doesn’t look like vaccines will be the worry with this variant. Rather, it could be competing with B.1.1.7 and could lead to breakthrough infections in vaccinated people or reinfections in unvaccinated people who had COVID-19. We need several more weeks to sort it out.
Although the B.1.427 and B.1.429 variants initially seen in California remain on the CDC’s concern list, I’m not worried about them.
You mentioned the current COVID-19 crisis in India, where a new variant has been described as a “double mutant,” but on Twitter you called it a “scariant.” Why?
First of all, the B.1.617 variant isn’t a double mutant. It has 15 mutations. It’s a stupid term, focusing on two mutations which largely have been put aside as to concern. One of them is the L452R, which is the same as one of the California variants, and that hasn’t proved to be particularly serious or concerning. The other is the 484Q, and it’s not clear whether that has any function.
The B.1.617 is not the driver of the catastrophe in India. It may be contributing a small amount, but it has been overhyped as the double mutant that’s causing it all. Adding to that are what I call “scariant” headlines here in the United States when a few cases of that variant have been seen.
I coined the term scariant in early February because it was a pretty clear trend. People don’t know what variants are. They know a little bit about mutations but not variants, and they’re scared. A few variants are concerning, but we keep learning more and more things to decrease the concern. That’s why I wrote the New York Times op-ed, to try to provide some reassurance, since there’s such paranoia.
Do you think booster vaccinations will be necessary? If so, will those be of the original vaccines or new ones that incorporate the variants?
As we go forward, there’s still potential for new variants that we haven’t seen yet that combine the worst of all features – transmissibility and immune evasion – especially since we have a world where COVID-19 is unchecked. So, we’re not out of it yet, but at least for the moment, we have vaccines that are capable of protecting against all variants.
In most people, the immune response against SARS-CoV-2 is very durable and strong and may well last for years. With the most closely related SARS-CoV-1, people still had immune responses up to 18 years later. However, some people will have less robust vaccine responses, including the elderly and the immunocompromised. If they don’t have great responses to the vaccine to start with, over time they’re likely to become more vulnerable, especially if they’re exposed to the variants with some degree of immune evasion.
I think we need to study these individuals post vaccination. A lot of people fit into those categories, including seniors, people being treated for cancer or autoimmune conditions, or post organ transplant. We could set up a prospective study to see whether they develop symptomatic COVID-19 and if so, from what – the original strain, B.1.1.7, or the newer variants.
That’s where I think booster shots may be needed. They may not be necessary across the board, but perhaps just in these special subgroups.
All of the current vaccines can be tweaked to include new variants, but the need for that is uncertain as of now. Moderna is working on a so-called bivalent vaccine that includes the original SARS-CoV-2 strain plus the B.1.351 variant, but it isn’t clear that that’s going to be necessary.
Currently, at least 200 COVID-19 vaccines are in development. There will be vaccines you can inhale, room temperature mRNA vaccines, and potentially even oral vaccines.
In the near future, Novavax is close, and there will likely be a two-dose Johnson & Johnson version that has the same potency as the mRNA vaccines. There are a lot of moving parts here.
There may be a step down in efficacy from mRNA to the others, though, and that shouldn’t be discounted. All of the available vaccines so far protect very well against severe disease and death, but some are less effective against mild to moderate infections, which may then lead to long COVID. We don’t yet know whether those who get mild infection post vaccination can still get long COVID.
What do you think it will take to achieve herd immunity?
I prefer the term “containment.” It’s quantitative. If you get to an infection rate of less than 1 in 100,000 people, as they’ve done in Israel, with 0.8 per 100,000, then you have the virus in check, and there will be very little spread when it’s at that controlled rate, with no outbreaks. The United States is currently at about 15 per 100,000. California is at 4. That still has to get lower.
It will be a challenge to get to President Biden’s goal of having 70% of U.S. adults given at least one dose by July 4. We’re now at about 57%. To get that next 13% of adults is going to take an all-out effort: mobile units, going to homes, making it ultraconvenient, education for people with safety concerns, incentivization, and days off.
We also need to get employers, universities, and health systems to get to the mandatory level. We haven’t done that yet. Some universities have mandated it for students, faculty, and staff. We need it in more health care systems. Right now, we only have a couple. We mandate flu shots, and flu is nothing, compared with COVID-19. And the COVID-19 vaccine is far more efficacious – flu shots are 40% efficacious, while these are 95%. COVID-19 is a tenfold more lethal and serious disease, and much more spreadable.
People are using the lack of full licensure by the Food and Drug Administration – as opposed to emergency use authorization – as an excuse not to get vaccinated. A biologics license application takes time to approve. Meanwhile, we have hundreds of millions of doses that have been well tolerated and incredibly effective.
Another aspect to consider regarding containment is that about 110 million Americans have already had COVID-19, even though only about 30 million cases have been confirmed. Most of these people have immune protection, although it’s not as good as if they have one vaccine dose. But they have enough protection to be part of the story here of the wall against COVID-19 and will help us get through this.
That’s a silver lining of having an unchecked epidemic for the entire year of 2020. The good part is that’s helping to get us to achieve an incredible level of containment when we haven’t even been close. Right now, we’re as good as the country has been in the pandemic, but we still have a long gap to get down to that 1 per 100,000. That’s what we should be working toward, and we can get there.
A version of this article first appeared on Medscape.com.
Infective endocarditis with stroke after TAVR has ‘dismal’ prognosis
Patients who suffer a stroke during hospitalization for infective endocarditis (IE) after transcatheter aortic valve replacement (TAVR) have a dismal prognosis, with more than half dying during the index hospitalization and two-thirds within the first year, a new study shows.
The study – the first to evaluate stroke as an IE-related complication following TAVR in a large multicenter cohort – is published in the May 11 issue of the Journal of the American College of Cardiology.
The authors, led by David del Val, MD, Quebec Heart & Lung Institute, Quebec City, explain that IE after TAVR is a rare but serious complication associated with a high mortality rate. Neurologic events, especially stroke, remain one of the most common and potentially disabling IE-related complications, but until now, no study has attempted to evaluate the predictors of stroke and outcomes in patients with IE following TAVR.
For the current study, the authors analyzed data from the Infectious Endocarditis after TAVR International Registry, including 569 patients who developed definite IE following TAVR from 59 centers in 11 countries.
Patients who experienced a stroke during IE admission were compared with patients who did not have a stroke.
Results showed that 57 patients (10%) had a stroke during IE hospitalization, with no differences in the causative microorganism between groups. Stroke patients had higher rates of acute renal failure, systemic embolization, and persistent bacteremia.
Factors associated with a higher risk for stroke during the index IE hospitalization included stroke before IE, moderate or higher residual aortic regurgitation after TAVR, balloon-expandable valves, IE within 30 days after TAVR, and vegetation size greater than 8 mm.
The stroke rate was 3.1% in patients with none of these risk factors; 6.1% with one risk factor; 13.1% with two risk factors; 28.9% with three risk factors, and 60% with four risk factors.
“The presence of such factors (particularly in combination) may be considered for determining an earlier and more aggressive (medical or surgical) treatment in these patients,” the researchers say.
IE patients with stroke had higher rates of in-hospital mortality (54.4% vs. 28.7%) and overall mortality at 1 year (66.3% vs. 45.6%).
Surgery rates were low (25%) even in the presence of stroke and failed to improve outcomes in this population.
Noting that consensus guidelines for managing patients with IE recommend surgery along with antibiotic treatment for patients developing systemic embolism, particularly stroke, the researchers say their findings suggest that such surgery recommendations may not be extrapolated to TAVR-IE patients, and specific guidelines are warranted for this particular population.
Furthermore, the possibility of early surgery in those patients with factors increasing the risk for stroke should be evaluated in future studies.
The authors note that TAVR has revolutionized the treatment of aortic stenosis and is currently moving toward less complex and younger patients with lower surgical risk. Despite the relatively low incidence of IE after TAVR, the number of procedures is expected to grow exponentially, increasing the number of patients at risk of developing this life-threatening complication. Therefore, detailed knowledge of this disease and its complications is essential to improve outcomes.
They point out that the 10% rate of stroke found in this study is substantially lower, compared with the largest surgical prosthetic-valve infective endocarditis registries, but they suggest that the unique clinical profile of TAVR patients may lead to an underdiagnosis of stroke, with a high proportion of elderly patients who more frequently present with nonspecific symptoms.
They conclude that “IE post-TAVR is associated with a poor prognosis with high in-hospital and late mortality rates. Our study reveals that patients with IE after TAVR complicated by stroke showed an even worse prognosis.”
“The progressive implementation of advanced imaging modalities for early IE diagnosis, especially nuclear imaging, may translate into a better prognosis in coming years. Close attention should be paid to early recognition of stroke-associated factors to improve clinical outcomes,” they add.
In an accompanying editorial, Vuyisile Nkomo, MD, Daniel DeSimone, MD, and William Miranda, MD, Mayo Clinic, Rochester, Minn., say the current study “highlights the devastating consequences of IE after TAVR and the even worse consequences when IE was associated with stroke.”
This points to the critical importance of efforts to prevent IE with appropriate antibiotic prophylaxis and addressing potential sources of infection (for example, dental screening) before invasive cardiac procedures.
“Patient education is critical in regard to recognizing early signs and symptoms of IE. In particular, patients must be informed to obtain blood cultures with any episode of fever, as identification of bacteremia is critical in the diagnosis of IE,” the editorialists comment.
Endocarditis should also be suspected in afebrile patients with increasing transcatheter heart valve gradients or new or worsening regurgitation, they state.
Multimodality imaging is important for the early diagnosis of IE to facilitate prompt antibiotic treatment and potentially decrease the risk for IE complications, especially systemic embolization, they add.
“Despite the unequivocal advances in the safety and periprocedural complications of TAVR, IE with and without stroke in this TAVR population remains a dreadful complication,” they conclude.
Dr. Del Val was supported by a research grant from the Fundación Alfonso Martin Escudero. The editorialists have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Patients who suffer a stroke during hospitalization for infective endocarditis (IE) after transcatheter aortic valve replacement (TAVR) have a dismal prognosis, with more than half dying during the index hospitalization and two-thirds within the first year, a new study shows.
The study – the first to evaluate stroke as an IE-related complication following TAVR in a large multicenter cohort – is published in the May 11 issue of the Journal of the American College of Cardiology.
The authors, led by David del Val, MD, Quebec Heart & Lung Institute, Quebec City, explain that IE after TAVR is a rare but serious complication associated with a high mortality rate. Neurologic events, especially stroke, remain one of the most common and potentially disabling IE-related complications, but until now, no study has attempted to evaluate the predictors of stroke and outcomes in patients with IE following TAVR.
For the current study, the authors analyzed data from the Infectious Endocarditis after TAVR International Registry, including 569 patients who developed definite IE following TAVR from 59 centers in 11 countries.
Patients who experienced a stroke during IE admission were compared with patients who did not have a stroke.
Results showed that 57 patients (10%) had a stroke during IE hospitalization, with no differences in the causative microorganism between groups. Stroke patients had higher rates of acute renal failure, systemic embolization, and persistent bacteremia.
Factors associated with a higher risk for stroke during the index IE hospitalization included stroke before IE, moderate or higher residual aortic regurgitation after TAVR, balloon-expandable valves, IE within 30 days after TAVR, and vegetation size greater than 8 mm.
The stroke rate was 3.1% in patients with none of these risk factors; 6.1% with one risk factor; 13.1% with two risk factors; 28.9% with three risk factors, and 60% with four risk factors.
“The presence of such factors (particularly in combination) may be considered for determining an earlier and more aggressive (medical or surgical) treatment in these patients,” the researchers say.
IE patients with stroke had higher rates of in-hospital mortality (54.4% vs. 28.7%) and overall mortality at 1 year (66.3% vs. 45.6%).
Surgery rates were low (25%) even in the presence of stroke and failed to improve outcomes in this population.
Noting that consensus guidelines for managing patients with IE recommend surgery along with antibiotic treatment for patients developing systemic embolism, particularly stroke, the researchers say their findings suggest that such surgery recommendations may not be extrapolated to TAVR-IE patients, and specific guidelines are warranted for this particular population.
Furthermore, the possibility of early surgery in those patients with factors increasing the risk for stroke should be evaluated in future studies.
The authors note that TAVR has revolutionized the treatment of aortic stenosis and is currently moving toward less complex and younger patients with lower surgical risk. Despite the relatively low incidence of IE after TAVR, the number of procedures is expected to grow exponentially, increasing the number of patients at risk of developing this life-threatening complication. Therefore, detailed knowledge of this disease and its complications is essential to improve outcomes.
They point out that the 10% rate of stroke found in this study is substantially lower, compared with the largest surgical prosthetic-valve infective endocarditis registries, but they suggest that the unique clinical profile of TAVR patients may lead to an underdiagnosis of stroke, with a high proportion of elderly patients who more frequently present with nonspecific symptoms.
They conclude that “IE post-TAVR is associated with a poor prognosis with high in-hospital and late mortality rates. Our study reveals that patients with IE after TAVR complicated by stroke showed an even worse prognosis.”
“The progressive implementation of advanced imaging modalities for early IE diagnosis, especially nuclear imaging, may translate into a better prognosis in coming years. Close attention should be paid to early recognition of stroke-associated factors to improve clinical outcomes,” they add.
In an accompanying editorial, Vuyisile Nkomo, MD, Daniel DeSimone, MD, and William Miranda, MD, Mayo Clinic, Rochester, Minn., say the current study “highlights the devastating consequences of IE after TAVR and the even worse consequences when IE was associated with stroke.”
This points to the critical importance of efforts to prevent IE with appropriate antibiotic prophylaxis and addressing potential sources of infection (for example, dental screening) before invasive cardiac procedures.
“Patient education is critical in regard to recognizing early signs and symptoms of IE. In particular, patients must be informed to obtain blood cultures with any episode of fever, as identification of bacteremia is critical in the diagnosis of IE,” the editorialists comment.
Endocarditis should also be suspected in afebrile patients with increasing transcatheter heart valve gradients or new or worsening regurgitation, they state.
Multimodality imaging is important for the early diagnosis of IE to facilitate prompt antibiotic treatment and potentially decrease the risk for IE complications, especially systemic embolization, they add.
“Despite the unequivocal advances in the safety and periprocedural complications of TAVR, IE with and without stroke in this TAVR population remains a dreadful complication,” they conclude.
Dr. Del Val was supported by a research grant from the Fundación Alfonso Martin Escudero. The editorialists have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Patients who suffer a stroke during hospitalization for infective endocarditis (IE) after transcatheter aortic valve replacement (TAVR) have a dismal prognosis, with more than half dying during the index hospitalization and two-thirds within the first year, a new study shows.
The study – the first to evaluate stroke as an IE-related complication following TAVR in a large multicenter cohort – is published in the May 11 issue of the Journal of the American College of Cardiology.
The authors, led by David del Val, MD, Quebec Heart & Lung Institute, Quebec City, explain that IE after TAVR is a rare but serious complication associated with a high mortality rate. Neurologic events, especially stroke, remain one of the most common and potentially disabling IE-related complications, but until now, no study has attempted to evaluate the predictors of stroke and outcomes in patients with IE following TAVR.
For the current study, the authors analyzed data from the Infectious Endocarditis after TAVR International Registry, including 569 patients who developed definite IE following TAVR from 59 centers in 11 countries.
Patients who experienced a stroke during IE admission were compared with patients who did not have a stroke.
Results showed that 57 patients (10%) had a stroke during IE hospitalization, with no differences in the causative microorganism between groups. Stroke patients had higher rates of acute renal failure, systemic embolization, and persistent bacteremia.
Factors associated with a higher risk for stroke during the index IE hospitalization included stroke before IE, moderate or higher residual aortic regurgitation after TAVR, balloon-expandable valves, IE within 30 days after TAVR, and vegetation size greater than 8 mm.
The stroke rate was 3.1% in patients with none of these risk factors; 6.1% with one risk factor; 13.1% with two risk factors; 28.9% with three risk factors, and 60% with four risk factors.
“The presence of such factors (particularly in combination) may be considered for determining an earlier and more aggressive (medical or surgical) treatment in these patients,” the researchers say.
IE patients with stroke had higher rates of in-hospital mortality (54.4% vs. 28.7%) and overall mortality at 1 year (66.3% vs. 45.6%).
Surgery rates were low (25%) even in the presence of stroke and failed to improve outcomes in this population.
Noting that consensus guidelines for managing patients with IE recommend surgery along with antibiotic treatment for patients developing systemic embolism, particularly stroke, the researchers say their findings suggest that such surgery recommendations may not be extrapolated to TAVR-IE patients, and specific guidelines are warranted for this particular population.
Furthermore, the possibility of early surgery in those patients with factors increasing the risk for stroke should be evaluated in future studies.
The authors note that TAVR has revolutionized the treatment of aortic stenosis and is currently moving toward less complex and younger patients with lower surgical risk. Despite the relatively low incidence of IE after TAVR, the number of procedures is expected to grow exponentially, increasing the number of patients at risk of developing this life-threatening complication. Therefore, detailed knowledge of this disease and its complications is essential to improve outcomes.
They point out that the 10% rate of stroke found in this study is substantially lower, compared with the largest surgical prosthetic-valve infective endocarditis registries, but they suggest that the unique clinical profile of TAVR patients may lead to an underdiagnosis of stroke, with a high proportion of elderly patients who more frequently present with nonspecific symptoms.
They conclude that “IE post-TAVR is associated with a poor prognosis with high in-hospital and late mortality rates. Our study reveals that patients with IE after TAVR complicated by stroke showed an even worse prognosis.”
“The progressive implementation of advanced imaging modalities for early IE diagnosis, especially nuclear imaging, may translate into a better prognosis in coming years. Close attention should be paid to early recognition of stroke-associated factors to improve clinical outcomes,” they add.
In an accompanying editorial, Vuyisile Nkomo, MD, Daniel DeSimone, MD, and William Miranda, MD, Mayo Clinic, Rochester, Minn., say the current study “highlights the devastating consequences of IE after TAVR and the even worse consequences when IE was associated with stroke.”
This points to the critical importance of efforts to prevent IE with appropriate antibiotic prophylaxis and addressing potential sources of infection (for example, dental screening) before invasive cardiac procedures.
“Patient education is critical in regard to recognizing early signs and symptoms of IE. In particular, patients must be informed to obtain blood cultures with any episode of fever, as identification of bacteremia is critical in the diagnosis of IE,” the editorialists comment.
Endocarditis should also be suspected in afebrile patients with increasing transcatheter heart valve gradients or new or worsening regurgitation, they state.
Multimodality imaging is important for the early diagnosis of IE to facilitate prompt antibiotic treatment and potentially decrease the risk for IE complications, especially systemic embolization, they add.
“Despite the unequivocal advances in the safety and periprocedural complications of TAVR, IE with and without stroke in this TAVR population remains a dreadful complication,” they conclude.
Dr. Del Val was supported by a research grant from the Fundación Alfonso Martin Escudero. The editorialists have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
VARC-3 sets goalpost for future aortic valve trials
The newly updated Valve Academic Research Consortium 3 (VARC-3) definitions and endpoints proposed for transcatheter and surgical aortic valve replacement (TAVR/SAVR) research aim to add more granularity and a patient focus to a rapidly evolving field, the authors say.
Work began in 2016 to update definitions in the document to be more contemporary, as TAVR matured over the last 10 years to include younger, lower-risk patients and began moving to long-term outcomes, lead author Philippe Généreux, MD, said in an interview.
“The main change in VARC-3 is really that we tried to define not only procedural outcome, both for TAVR and aortic valve replacement performed by surgery, but also more the long-term outcomes mainly based on the patient – so quality of life, bioprosthetic valve failure, how do we define a valve failure, and also the need for rehospitalization,” he said.
However, soon after the VARC-3 document was published on April 19, 2021, in the European Heart Journal and Journal of the American College of Cardiology, surgeons took to social media to highlight the writing committee’s financial ties to industry and to suggest some definitions were shaped to favor transcatheter approaches.
“There’s no doubt that the coauthors who participated in these guidelines are experts; nobody would argue about that but what we can argue, and I’m 100% sure about, is that we have experts outside the payroll of industry who are excellent and can be part of this guideline drafting in an unbiased way,” Victor Dayan, MD, adjunct professor of cardiac surgery, National Institute of Cardiac Surgery, Montevideo, Uruguay, said in an interview.
Although the American College of Physicians recommends guideline committee members with moderate- or high-level conflicts of interest recuse themselves from authorship, he noted that one author has received more than $2 million in fees from industry in the past 4-5 years.
In all, 20 of 23 authors were involved in PARTNER, SURTAVI, and PORTICO, and several also write clinical guidelines for the American College of Cardiology and American Heart Association. “So we have the same authors that are judge, jury, and attorney for these issues,” Dr. Dayan said.
In a comment, J. Rafael Sádaba, MD, PhD, interim secretary general for the European Association for Cardio-Thoracic Surgery, pointed out that only three committee members are surgeons and that author disclosures took up nearly a full page of the document. “Surely they would be able to find very capable physicians with far less conflicts of interest.”
Dr. Sádaba said the question to him is why professional societies like ACC and AHA don’t define the endpoints for the clinical trials that will inform their guidelines.
“One could say these people are there because they’re good scientists, trialists, but one at least has to ask why is this happening. Why are these people setting the rules for the trials they’re running?” said Dr. Sádaba, of the Royal Navarre Hospital, Pamplona, Spain.
Dr. Généreux dismissed the Twitter comments as coming from a handful of people who engage in conspiracy theories. The VARC-3 document, he said, was created with input from 75 experts, including Food and Drug Administration officials, and the final document was reviewed by the FDA and underwent rigorous peer review prior to publication.
“The question is: do you believe there is bias when people are involved in studies driven by the industry? Well, this is where we derive our science in this field,” he said. “We are very transparent and disclose our conflicts of interest [COI].”
Commenting further, Dr. Généreux added, “this was a very well-balanced group and to imply that because we work with industry, we don’t have the best interest of the patient in mind is wrong.”
Editor in chief of the EHJ, Filippo Crea, MD, PhD, Catholic University, Rome, said in an comment that “it is not surprising that most of the authors have experience in TAVR trials. All of the authors have carefully disclosed their COIs.”
He noted that the EHJ and JACC copublished the first VARC consensus in 2011, VARC-2 1 year later, and that VARC-3 was reviewed by four external reviewers and two editors and was accepted for publication after two revisions.
Asked about a shot on social media that the EHJ had long ago “sold its soul” to be the scientific “arm” of industry, Dr. Crea said allegations need to be substantiated by facts.
“The wide adoption of VARC definitions implies that they have been well accepted by the scientific community and that they have stood the test of time,” Dr. Crea said. “EHJ has a history of publishing high-quality science. We welcome robust arguments that may challenge previously published work. Readers who perceive gaps are encouraged to provide a detailed challenge and engage with the journal.”
Defining hospitalizations
One of the surgeons’ biggest concerns is that VARC-3 now defines hospitalization or rehospitalization as “any admission after the index hospitalization or study enrollment” for at least 24 hours, including an ED stay.
VARC-2 and SURTAVI defined hospitalizations as those for valve-related symptoms or worsening heart failure, whereas the newly reformulated definition of hospitalization was part of the main composite endpoint in the PARTNER-3 trial, along with stroke and mortality, that drove the superiority of TAVR over SAVR at 1 year for low-risk patients, Dr. Dayan noted.
“It’s not uncommon for patients who have cardiac surgery to come back for issues related to wound healing or mild pulmonary edema for a day or 2, and if you include these hospitalizations in the primary endpoint, it will dilute the real benefit of SAVR versus TAVR, which is mortality and stroke,” he added.
In choosing the broader definition, Dr. Généreux said they borrowed from heart failure studies that take a granular approach and account for every hospitalization, be it for a medication change or adjustment. “We cannot pick and choose which hospitalization we are going to consider or ignore.”
VARC-3 proposes criteria for identifying and diagnosing hypoattenuated leaflet thickening (HALT) and reduced leaflet motion and features a detailed chart of the new classification scheme for bioprosthetic valve dysfunction and failure.
Bioprosthetic valve dysfunction includes structural valve deterioration, nonstructural valve dysfunction (including abnormalities not intrinsic to the valve such as paravalvular regurgitation or prosthesis-patient mismatch), thrombosis, and endocarditis. VARC-3 proposes a five-class grading system for paravalvular regurgitation (mild, mild-moderate, moderate, moderate-severe, severe).
The document updates what the authors called a “previously vague definition” of valve thrombosis proposed in 2011 to now include “clinically significant” prosthetic valve thrombosis. This requires clinical sequelae of a thromboembolic event (stroke, transient ischemic attack, retinal occlusion, or other evidence of thromboembolism) or worsening valve stenosis/regurgitation and either hemodynamic valve deterioration stage 2 or 3 or confirmatory imaging (CT evidence of HALT or transesophageal echocardiographic findings). In the absence of symptoms/clinical sequelae, valve thrombosis (subclinical) can be diagnosed if there is hemodynamic valve deterioration stage 3 and confirmatory imaging.
Bioprosthetic valve failure is divided into three stages, with stage 1 taking into account clinical factors along with valve dysfunction, stage 2 being reintervention, and stage 3 being valve-related death.
“For us, bioprosthesis valve failure is not only the need for reintervention, but it’s also mortality, it’s also a significant increase in gradient or the occurrence of paravalvular leak,” said Dr. Généreux, of the Morristown (N.J.) Medical Center. “So it’s much more clinical.”
Stroke, myocardial infarction
VARC-3 provides detailed definitions of neurologic events and, in an attempt to harmonize with the Neurologic Academic Research Consortium, recommends combining assessment of neurologic symptoms with tissue-based criteria (pathology or neuroimaging, ideally diffusion-weighted MRI) to define stroke and other central nervous system injury.
It also recommends that assessment be performed 30-90 days after a neurologic event and that assessment of neurologic deficits for cerebral embolic protection trials be performed by a neurologist.
VARC-3 endorses the fourth Universal Definition of Myocardial Infarction for MI types 1-3, 4B, and 4C.
For periprocedural MI after percutaneous coronary intervention (PCI), coronary bypass graft surgery, TAVR, and SAVR, however, it endorses the modified Society for Cardiovascular Angiography and Interventions and Academic Research Consortium-2 definition, which uses troponin or creatine kinase-MB thresholds.
“Given that most current and future studies related to AVR strategies will involve long-term follow-up, with patients frequently suffering from coronary artery disease, VARC-3 believes that these definitions will allow the most appropriate characterization and classification of types of MI occurring in this population,” the committee wrote.
The decision comes after last year’s controversy surrounding the Abbott-sponsored EXCEL trial, which used a modified version of the SCAI definition for periprocedural MI as part of its primary composite endpoint of death, stroke, and MI.
Initial reports showed nearly twice the rate of periprocedural MI with cardiac surgery as with PCI, but after a BBC investigation involving leaked data and an onslaught of criticism from surgeons, later results using the third universal definition showed surgery had the advantage.
The debacle frayed relations between surgeons and interventionalists and prompted EACTS to withdraw its support for treatment recommendations for left main coronary artery disease.
Dr. Dayan applauded VARC-3 for incorporating more detailed information on stroke and neurologic events, but said the use of the SCAI definition in the final published document is in “total disregard” to the controversy generated among surgeons and interventionalists.
“The main concern for surgeons is defining periprocedural MI just by biochemical definitions, without any additional criteria like ECG, angiographic,” he said. “This is totally new and goes against what surgeons have been advocating for years around EXCEL.”
Dr. Sádaba was troubled by the definitions of MI and hospitalization, but also questioned other changes, like lumping vascular complications together with access-related complications. “The sense is a lot of what they’ve put here favors one type of intervention over the other.”
Dr. Généreux reported receiving consultant fees from Abbott Vascular, Abiomed, Boston Scientific, Cardinal Health, Cardiovascular System, Edwards Lifesciences, Medtronic, Opsens, Siemens, SoundBite Medical Solutions, Sig.Num, Saranas, Teleflex, Tryton Medical, and has equity in Pi-Cardia, Sig.Num, SoundBite Medical Solutions, Saranas, and Puzzle Medical. Dr. Crea reported receiving personal fees from Novartis, Bristol-Myers Squibb, Amgen, and AstraZeneca, and is a member of the advisory board of GlyCardial Diagnostics. Dr. Dayan and Dr. Sádaba reported no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
The newly updated Valve Academic Research Consortium 3 (VARC-3) definitions and endpoints proposed for transcatheter and surgical aortic valve replacement (TAVR/SAVR) research aim to add more granularity and a patient focus to a rapidly evolving field, the authors say.
Work began in 2016 to update definitions in the document to be more contemporary, as TAVR matured over the last 10 years to include younger, lower-risk patients and began moving to long-term outcomes, lead author Philippe Généreux, MD, said in an interview.
“The main change in VARC-3 is really that we tried to define not only procedural outcome, both for TAVR and aortic valve replacement performed by surgery, but also more the long-term outcomes mainly based on the patient – so quality of life, bioprosthetic valve failure, how do we define a valve failure, and also the need for rehospitalization,” he said.
However, soon after the VARC-3 document was published on April 19, 2021, in the European Heart Journal and Journal of the American College of Cardiology, surgeons took to social media to highlight the writing committee’s financial ties to industry and to suggest some definitions were shaped to favor transcatheter approaches.
“There’s no doubt that the coauthors who participated in these guidelines are experts; nobody would argue about that but what we can argue, and I’m 100% sure about, is that we have experts outside the payroll of industry who are excellent and can be part of this guideline drafting in an unbiased way,” Victor Dayan, MD, adjunct professor of cardiac surgery, National Institute of Cardiac Surgery, Montevideo, Uruguay, said in an interview.
Although the American College of Physicians recommends guideline committee members with moderate- or high-level conflicts of interest recuse themselves from authorship, he noted that one author has received more than $2 million in fees from industry in the past 4-5 years.
In all, 20 of 23 authors were involved in PARTNER, SURTAVI, and PORTICO, and several also write clinical guidelines for the American College of Cardiology and American Heart Association. “So we have the same authors that are judge, jury, and attorney for these issues,” Dr. Dayan said.
In a comment, J. Rafael Sádaba, MD, PhD, interim secretary general for the European Association for Cardio-Thoracic Surgery, pointed out that only three committee members are surgeons and that author disclosures took up nearly a full page of the document. “Surely they would be able to find very capable physicians with far less conflicts of interest.”
Dr. Sádaba said the question to him is why professional societies like ACC and AHA don’t define the endpoints for the clinical trials that will inform their guidelines.
“One could say these people are there because they’re good scientists, trialists, but one at least has to ask why is this happening. Why are these people setting the rules for the trials they’re running?” said Dr. Sádaba, of the Royal Navarre Hospital, Pamplona, Spain.
Dr. Généreux dismissed the Twitter comments as coming from a handful of people who engage in conspiracy theories. The VARC-3 document, he said, was created with input from 75 experts, including Food and Drug Administration officials, and the final document was reviewed by the FDA and underwent rigorous peer review prior to publication.
“The question is: do you believe there is bias when people are involved in studies driven by the industry? Well, this is where we derive our science in this field,” he said. “We are very transparent and disclose our conflicts of interest [COI].”
Commenting further, Dr. Généreux added, “this was a very well-balanced group and to imply that because we work with industry, we don’t have the best interest of the patient in mind is wrong.”
Editor in chief of the EHJ, Filippo Crea, MD, PhD, Catholic University, Rome, said in an comment that “it is not surprising that most of the authors have experience in TAVR trials. All of the authors have carefully disclosed their COIs.”
He noted that the EHJ and JACC copublished the first VARC consensus in 2011, VARC-2 1 year later, and that VARC-3 was reviewed by four external reviewers and two editors and was accepted for publication after two revisions.
Asked about a shot on social media that the EHJ had long ago “sold its soul” to be the scientific “arm” of industry, Dr. Crea said allegations need to be substantiated by facts.
“The wide adoption of VARC definitions implies that they have been well accepted by the scientific community and that they have stood the test of time,” Dr. Crea said. “EHJ has a history of publishing high-quality science. We welcome robust arguments that may challenge previously published work. Readers who perceive gaps are encouraged to provide a detailed challenge and engage with the journal.”
Defining hospitalizations
One of the surgeons’ biggest concerns is that VARC-3 now defines hospitalization or rehospitalization as “any admission after the index hospitalization or study enrollment” for at least 24 hours, including an ED stay.
VARC-2 and SURTAVI defined hospitalizations as those for valve-related symptoms or worsening heart failure, whereas the newly reformulated definition of hospitalization was part of the main composite endpoint in the PARTNER-3 trial, along with stroke and mortality, that drove the superiority of TAVR over SAVR at 1 year for low-risk patients, Dr. Dayan noted.
“It’s not uncommon for patients who have cardiac surgery to come back for issues related to wound healing or mild pulmonary edema for a day or 2, and if you include these hospitalizations in the primary endpoint, it will dilute the real benefit of SAVR versus TAVR, which is mortality and stroke,” he added.
In choosing the broader definition, Dr. Généreux said they borrowed from heart failure studies that take a granular approach and account for every hospitalization, be it for a medication change or adjustment. “We cannot pick and choose which hospitalization we are going to consider or ignore.”
VARC-3 proposes criteria for identifying and diagnosing hypoattenuated leaflet thickening (HALT) and reduced leaflet motion and features a detailed chart of the new classification scheme for bioprosthetic valve dysfunction and failure.
Bioprosthetic valve dysfunction includes structural valve deterioration, nonstructural valve dysfunction (including abnormalities not intrinsic to the valve such as paravalvular regurgitation or prosthesis-patient mismatch), thrombosis, and endocarditis. VARC-3 proposes a five-class grading system for paravalvular regurgitation (mild, mild-moderate, moderate, moderate-severe, severe).
The document updates what the authors called a “previously vague definition” of valve thrombosis proposed in 2011 to now include “clinically significant” prosthetic valve thrombosis. This requires clinical sequelae of a thromboembolic event (stroke, transient ischemic attack, retinal occlusion, or other evidence of thromboembolism) or worsening valve stenosis/regurgitation and either hemodynamic valve deterioration stage 2 or 3 or confirmatory imaging (CT evidence of HALT or transesophageal echocardiographic findings). In the absence of symptoms/clinical sequelae, valve thrombosis (subclinical) can be diagnosed if there is hemodynamic valve deterioration stage 3 and confirmatory imaging.
Bioprosthetic valve failure is divided into three stages, with stage 1 taking into account clinical factors along with valve dysfunction, stage 2 being reintervention, and stage 3 being valve-related death.
“For us, bioprosthesis valve failure is not only the need for reintervention, but it’s also mortality, it’s also a significant increase in gradient or the occurrence of paravalvular leak,” said Dr. Généreux, of the Morristown (N.J.) Medical Center. “So it’s much more clinical.”
Stroke, myocardial infarction
VARC-3 provides detailed definitions of neurologic events and, in an attempt to harmonize with the Neurologic Academic Research Consortium, recommends combining assessment of neurologic symptoms with tissue-based criteria (pathology or neuroimaging, ideally diffusion-weighted MRI) to define stroke and other central nervous system injury.
It also recommends that assessment be performed 30-90 days after a neurologic event and that assessment of neurologic deficits for cerebral embolic protection trials be performed by a neurologist.
VARC-3 endorses the fourth Universal Definition of Myocardial Infarction for MI types 1-3, 4B, and 4C.
For periprocedural MI after percutaneous coronary intervention (PCI), coronary bypass graft surgery, TAVR, and SAVR, however, it endorses the modified Society for Cardiovascular Angiography and Interventions and Academic Research Consortium-2 definition, which uses troponin or creatine kinase-MB thresholds.
“Given that most current and future studies related to AVR strategies will involve long-term follow-up, with patients frequently suffering from coronary artery disease, VARC-3 believes that these definitions will allow the most appropriate characterization and classification of types of MI occurring in this population,” the committee wrote.
The decision comes after last year’s controversy surrounding the Abbott-sponsored EXCEL trial, which used a modified version of the SCAI definition for periprocedural MI as part of its primary composite endpoint of death, stroke, and MI.
Initial reports showed nearly twice the rate of periprocedural MI with cardiac surgery as with PCI, but after a BBC investigation involving leaked data and an onslaught of criticism from surgeons, later results using the third universal definition showed surgery had the advantage.
The debacle frayed relations between surgeons and interventionalists and prompted EACTS to withdraw its support for treatment recommendations for left main coronary artery disease.
Dr. Dayan applauded VARC-3 for incorporating more detailed information on stroke and neurologic events, but said the use of the SCAI definition in the final published document is in “total disregard” to the controversy generated among surgeons and interventionalists.
“The main concern for surgeons is defining periprocedural MI just by biochemical definitions, without any additional criteria like ECG, angiographic,” he said. “This is totally new and goes against what surgeons have been advocating for years around EXCEL.”
Dr. Sádaba was troubled by the definitions of MI and hospitalization, but also questioned other changes, like lumping vascular complications together with access-related complications. “The sense is a lot of what they’ve put here favors one type of intervention over the other.”
Dr. Généreux reported receiving consultant fees from Abbott Vascular, Abiomed, Boston Scientific, Cardinal Health, Cardiovascular System, Edwards Lifesciences, Medtronic, Opsens, Siemens, SoundBite Medical Solutions, Sig.Num, Saranas, Teleflex, Tryton Medical, and has equity in Pi-Cardia, Sig.Num, SoundBite Medical Solutions, Saranas, and Puzzle Medical. Dr. Crea reported receiving personal fees from Novartis, Bristol-Myers Squibb, Amgen, and AstraZeneca, and is a member of the advisory board of GlyCardial Diagnostics. Dr. Dayan and Dr. Sádaba reported no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
The newly updated Valve Academic Research Consortium 3 (VARC-3) definitions and endpoints proposed for transcatheter and surgical aortic valve replacement (TAVR/SAVR) research aim to add more granularity and a patient focus to a rapidly evolving field, the authors say.
Work began in 2016 to update definitions in the document to be more contemporary, as TAVR matured over the last 10 years to include younger, lower-risk patients and began moving to long-term outcomes, lead author Philippe Généreux, MD, said in an interview.
“The main change in VARC-3 is really that we tried to define not only procedural outcome, both for TAVR and aortic valve replacement performed by surgery, but also more the long-term outcomes mainly based on the patient – so quality of life, bioprosthetic valve failure, how do we define a valve failure, and also the need for rehospitalization,” he said.
However, soon after the VARC-3 document was published on April 19, 2021, in the European Heart Journal and Journal of the American College of Cardiology, surgeons took to social media to highlight the writing committee’s financial ties to industry and to suggest some definitions were shaped to favor transcatheter approaches.
“There’s no doubt that the coauthors who participated in these guidelines are experts; nobody would argue about that but what we can argue, and I’m 100% sure about, is that we have experts outside the payroll of industry who are excellent and can be part of this guideline drafting in an unbiased way,” Victor Dayan, MD, adjunct professor of cardiac surgery, National Institute of Cardiac Surgery, Montevideo, Uruguay, said in an interview.
Although the American College of Physicians recommends guideline committee members with moderate- or high-level conflicts of interest recuse themselves from authorship, he noted that one author has received more than $2 million in fees from industry in the past 4-5 years.
In all, 20 of 23 authors were involved in PARTNER, SURTAVI, and PORTICO, and several also write clinical guidelines for the American College of Cardiology and American Heart Association. “So we have the same authors that are judge, jury, and attorney for these issues,” Dr. Dayan said.
In a comment, J. Rafael Sádaba, MD, PhD, interim secretary general for the European Association for Cardio-Thoracic Surgery, pointed out that only three committee members are surgeons and that author disclosures took up nearly a full page of the document. “Surely they would be able to find very capable physicians with far less conflicts of interest.”
Dr. Sádaba said the question to him is why professional societies like ACC and AHA don’t define the endpoints for the clinical trials that will inform their guidelines.
“One could say these people are there because they’re good scientists, trialists, but one at least has to ask why is this happening. Why are these people setting the rules for the trials they’re running?” said Dr. Sádaba, of the Royal Navarre Hospital, Pamplona, Spain.
Dr. Généreux dismissed the Twitter comments as coming from a handful of people who engage in conspiracy theories. The VARC-3 document, he said, was created with input from 75 experts, including Food and Drug Administration officials, and the final document was reviewed by the FDA and underwent rigorous peer review prior to publication.
“The question is: do you believe there is bias when people are involved in studies driven by the industry? Well, this is where we derive our science in this field,” he said. “We are very transparent and disclose our conflicts of interest [COI].”
Commenting further, Dr. Généreux added, “this was a very well-balanced group and to imply that because we work with industry, we don’t have the best interest of the patient in mind is wrong.”
Editor in chief of the EHJ, Filippo Crea, MD, PhD, Catholic University, Rome, said in an comment that “it is not surprising that most of the authors have experience in TAVR trials. All of the authors have carefully disclosed their COIs.”
He noted that the EHJ and JACC copublished the first VARC consensus in 2011, VARC-2 1 year later, and that VARC-3 was reviewed by four external reviewers and two editors and was accepted for publication after two revisions.
Asked about a shot on social media that the EHJ had long ago “sold its soul” to be the scientific “arm” of industry, Dr. Crea said allegations need to be substantiated by facts.
“The wide adoption of VARC definitions implies that they have been well accepted by the scientific community and that they have stood the test of time,” Dr. Crea said. “EHJ has a history of publishing high-quality science. We welcome robust arguments that may challenge previously published work. Readers who perceive gaps are encouraged to provide a detailed challenge and engage with the journal.”
Defining hospitalizations
One of the surgeons’ biggest concerns is that VARC-3 now defines hospitalization or rehospitalization as “any admission after the index hospitalization or study enrollment” for at least 24 hours, including an ED stay.
VARC-2 and SURTAVI defined hospitalizations as those for valve-related symptoms or worsening heart failure, whereas the newly reformulated definition of hospitalization was part of the main composite endpoint in the PARTNER-3 trial, along with stroke and mortality, that drove the superiority of TAVR over SAVR at 1 year for low-risk patients, Dr. Dayan noted.
“It’s not uncommon for patients who have cardiac surgery to come back for issues related to wound healing or mild pulmonary edema for a day or 2, and if you include these hospitalizations in the primary endpoint, it will dilute the real benefit of SAVR versus TAVR, which is mortality and stroke,” he added.
In choosing the broader definition, Dr. Généreux said they borrowed from heart failure studies that take a granular approach and account for every hospitalization, be it for a medication change or adjustment. “We cannot pick and choose which hospitalization we are going to consider or ignore.”
VARC-3 proposes criteria for identifying and diagnosing hypoattenuated leaflet thickening (HALT) and reduced leaflet motion and features a detailed chart of the new classification scheme for bioprosthetic valve dysfunction and failure.
Bioprosthetic valve dysfunction includes structural valve deterioration, nonstructural valve dysfunction (including abnormalities not intrinsic to the valve such as paravalvular regurgitation or prosthesis-patient mismatch), thrombosis, and endocarditis. VARC-3 proposes a five-class grading system for paravalvular regurgitation (mild, mild-moderate, moderate, moderate-severe, severe).
The document updates what the authors called a “previously vague definition” of valve thrombosis proposed in 2011 to now include “clinically significant” prosthetic valve thrombosis. This requires clinical sequelae of a thromboembolic event (stroke, transient ischemic attack, retinal occlusion, or other evidence of thromboembolism) or worsening valve stenosis/regurgitation and either hemodynamic valve deterioration stage 2 or 3 or confirmatory imaging (CT evidence of HALT or transesophageal echocardiographic findings). In the absence of symptoms/clinical sequelae, valve thrombosis (subclinical) can be diagnosed if there is hemodynamic valve deterioration stage 3 and confirmatory imaging.
Bioprosthetic valve failure is divided into three stages, with stage 1 taking into account clinical factors along with valve dysfunction, stage 2 being reintervention, and stage 3 being valve-related death.
“For us, bioprosthesis valve failure is not only the need for reintervention, but it’s also mortality, it’s also a significant increase in gradient or the occurrence of paravalvular leak,” said Dr. Généreux, of the Morristown (N.J.) Medical Center. “So it’s much more clinical.”
Stroke, myocardial infarction
VARC-3 provides detailed definitions of neurologic events and, in an attempt to harmonize with the Neurologic Academic Research Consortium, recommends combining assessment of neurologic symptoms with tissue-based criteria (pathology or neuroimaging, ideally diffusion-weighted MRI) to define stroke and other central nervous system injury.
It also recommends that assessment be performed 30-90 days after a neurologic event and that assessment of neurologic deficits for cerebral embolic protection trials be performed by a neurologist.
VARC-3 endorses the fourth Universal Definition of Myocardial Infarction for MI types 1-3, 4B, and 4C.
For periprocedural MI after percutaneous coronary intervention (PCI), coronary bypass graft surgery, TAVR, and SAVR, however, it endorses the modified Society for Cardiovascular Angiography and Interventions and Academic Research Consortium-2 definition, which uses troponin or creatine kinase-MB thresholds.
“Given that most current and future studies related to AVR strategies will involve long-term follow-up, with patients frequently suffering from coronary artery disease, VARC-3 believes that these definitions will allow the most appropriate characterization and classification of types of MI occurring in this population,” the committee wrote.
The decision comes after last year’s controversy surrounding the Abbott-sponsored EXCEL trial, which used a modified version of the SCAI definition for periprocedural MI as part of its primary composite endpoint of death, stroke, and MI.
Initial reports showed nearly twice the rate of periprocedural MI with cardiac surgery as with PCI, but after a BBC investigation involving leaked data and an onslaught of criticism from surgeons, later results using the third universal definition showed surgery had the advantage.
The debacle frayed relations between surgeons and interventionalists and prompted EACTS to withdraw its support for treatment recommendations for left main coronary artery disease.
Dr. Dayan applauded VARC-3 for incorporating more detailed information on stroke and neurologic events, but said the use of the SCAI definition in the final published document is in “total disregard” to the controversy generated among surgeons and interventionalists.
“The main concern for surgeons is defining periprocedural MI just by biochemical definitions, without any additional criteria like ECG, angiographic,” he said. “This is totally new and goes against what surgeons have been advocating for years around EXCEL.”
Dr. Sádaba was troubled by the definitions of MI and hospitalization, but also questioned other changes, like lumping vascular complications together with access-related complications. “The sense is a lot of what they’ve put here favors one type of intervention over the other.”
Dr. Généreux reported receiving consultant fees from Abbott Vascular, Abiomed, Boston Scientific, Cardinal Health, Cardiovascular System, Edwards Lifesciences, Medtronic, Opsens, Siemens, SoundBite Medical Solutions, Sig.Num, Saranas, Teleflex, Tryton Medical, and has equity in Pi-Cardia, Sig.Num, SoundBite Medical Solutions, Saranas, and Puzzle Medical. Dr. Crea reported receiving personal fees from Novartis, Bristol-Myers Squibb, Amgen, and AstraZeneca, and is a member of the advisory board of GlyCardial Diagnostics. Dr. Dayan and Dr. Sádaba reported no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
Nutritional support may be lifesaving in heart failure
Personalized nutritional support for adults hospitalized with chronic heart failure and deemed to be at high nutritional risk reduced the risk of death or adverse cardiovascular events, compared with standard hospital food, new research indicates.
The Swiss EFFORT trial focused on patients with chronic heart failure and high risk of malnutrition defined by low body mass index, weight loss, and low food intake upon hospital admission.
“This high-risk group of chronic heart failure patients showed a significant improvement in mortality over 30 and 180 days, as well as other clinical outcomes, when individualized nutritional support interventions were offered to patients,” Philipp Schuetz, MD, MPH, Kantonsspital Aarau, Switzerland, said in an interview.
“While monitoring the nutritional status should be done also in outpatient settings by [general practitioners], malnutrition screening upon hospital admission may help to identify high-risk patients with high risk for nutritional status deterioration during the hospital stay who will benefit from nutritional assessment and treatment,” said Dr. Schuetz.
The study was published online May 3 in the Journal of the American College of Cardiology.
It’s not all about salt
The findings are based on a prespecified secondary analysis of outcomes in 645 patients (median age, 78.8 years, 52% men) hospitalized with chronic heart failure who participated in the open-label EFFORT study.
One-third of patients were hospitalized for acute decompensated heart failure and two-thirds had chronic heart failure and other acute medical illnesses requiring hospitalization.
All patients were at risk of malnutrition based on a Nutritional Risk Screening (NRS) score of 3 points or higher. They were randomly allocated 1:1 to individualized nutritional support to reach energy, protein, and micronutrient goals or usual hospital food (control group).
By 30 days, 27 of 321 patients (8.4%) receiving nutritional support had died compared with 48 of 324 patients (14.8%) in the control group (adjusted odds ratio [OR]: 0.44; 95% confidence interval, 0.26-0.75; P = .002)
Patients with high nutritional risk (NRS >4 points) showed the most benefit from nutritional support.
Compared with patients with moderate nutritional risk scores (NRS score 3-4), those with high nutritional risk (NRS >4) had a highly significant 65% increased mortality risk over 180 days.
The individual component of the NRS with the strongest association with mortality was low food intake in the week before hospitalization.
Patients who received nutritional support in the hospital also had a lower risk for major cardiovascular events at 30 days (17.4% vs. 26.9%; OR, 0.50; 95% CI, 0.34-0.75; P = .001).
“Historically, cardiologists and internists caring for patients with heart failure have mainly focused on salt-restrictive diets to reduce blood volume and thus optimize heart function. Yet, reduction of salt intake has not been shown to effectively improve clinical outcome but may, on the contrary, increase the risk of malnutrition as low-salt diets are often not tasty,” Dr. Schuetz said.
“Our data suggest that we should move our focus away from salt-restrictive diets to high-protein diets to cover individual nutritional goals in this high-risk group of patients, which includes screening, assessment, and nutritional support by dietitians,” Dr. Schuetz said.
In a linked editorial, Sheldon Gottlieb, MD, Johns Hopkins University, Baltimore, said there has been “relatively little attention” paid to the role of diet in heart failure other than recommending reduced salt intake.
In fact, in the 2021 American College of Cardiology expert consensus recommendations for optimizing heart failure treatment, roughly five words are devoted to diet and exercise and there is no mention of nutrition assessment by a dietitian, he points out.
“This study adds another tile to the still-fragmentary mosaic picture of the patient with heart failure at nutritional risk who might benefit from nutritional support,” Dr. Dr. Gottlieb wrote.
“ ‘Good medical care’ dictates that all hospitalized patients deserve to have a standardized nutritional assessment; the challenge remains: how to determine which patient with heart failure at nutritional risk will benefit by medical nutrition therapy,” Dr. Gottlieb said.
The Swiss National Science Foundation and the Research Council of the Kantonsspital Aarau provided funding for the trial. Dr. Schuetz’s institution has previously received unrestricted grant money unrelated to this project from Nestle Health Science and Abbott Nutrition. Dr. Gottlieb owns a federal trademark for the “Greens, Beans, and Leans” diet, and has a pending federal trademark for “FLOATS”: flax + oats cereal.
A version of this article first appeared on Medscape.com.
Personalized nutritional support for adults hospitalized with chronic heart failure and deemed to be at high nutritional risk reduced the risk of death or adverse cardiovascular events, compared with standard hospital food, new research indicates.
The Swiss EFFORT trial focused on patients with chronic heart failure and high risk of malnutrition defined by low body mass index, weight loss, and low food intake upon hospital admission.
“This high-risk group of chronic heart failure patients showed a significant improvement in mortality over 30 and 180 days, as well as other clinical outcomes, when individualized nutritional support interventions were offered to patients,” Philipp Schuetz, MD, MPH, Kantonsspital Aarau, Switzerland, said in an interview.
“While monitoring the nutritional status should be done also in outpatient settings by [general practitioners], malnutrition screening upon hospital admission may help to identify high-risk patients with high risk for nutritional status deterioration during the hospital stay who will benefit from nutritional assessment and treatment,” said Dr. Schuetz.
The study was published online May 3 in the Journal of the American College of Cardiology.
It’s not all about salt
The findings are based on a prespecified secondary analysis of outcomes in 645 patients (median age, 78.8 years, 52% men) hospitalized with chronic heart failure who participated in the open-label EFFORT study.
One-third of patients were hospitalized for acute decompensated heart failure and two-thirds had chronic heart failure and other acute medical illnesses requiring hospitalization.
All patients were at risk of malnutrition based on a Nutritional Risk Screening (NRS) score of 3 points or higher. They were randomly allocated 1:1 to individualized nutritional support to reach energy, protein, and micronutrient goals or usual hospital food (control group).
By 30 days, 27 of 321 patients (8.4%) receiving nutritional support had died compared with 48 of 324 patients (14.8%) in the control group (adjusted odds ratio [OR]: 0.44; 95% confidence interval, 0.26-0.75; P = .002)
Patients with high nutritional risk (NRS >4 points) showed the most benefit from nutritional support.
Compared with patients with moderate nutritional risk scores (NRS score 3-4), those with high nutritional risk (NRS >4) had a highly significant 65% increased mortality risk over 180 days.
The individual component of the NRS with the strongest association with mortality was low food intake in the week before hospitalization.
Patients who received nutritional support in the hospital also had a lower risk for major cardiovascular events at 30 days (17.4% vs. 26.9%; OR, 0.50; 95% CI, 0.34-0.75; P = .001).
“Historically, cardiologists and internists caring for patients with heart failure have mainly focused on salt-restrictive diets to reduce blood volume and thus optimize heart function. Yet, reduction of salt intake has not been shown to effectively improve clinical outcome but may, on the contrary, increase the risk of malnutrition as low-salt diets are often not tasty,” Dr. Schuetz said.
“Our data suggest that we should move our focus away from salt-restrictive diets to high-protein diets to cover individual nutritional goals in this high-risk group of patients, which includes screening, assessment, and nutritional support by dietitians,” Dr. Schuetz said.
In a linked editorial, Sheldon Gottlieb, MD, Johns Hopkins University, Baltimore, said there has been “relatively little attention” paid to the role of diet in heart failure other than recommending reduced salt intake.
In fact, in the 2021 American College of Cardiology expert consensus recommendations for optimizing heart failure treatment, roughly five words are devoted to diet and exercise and there is no mention of nutrition assessment by a dietitian, he points out.
“This study adds another tile to the still-fragmentary mosaic picture of the patient with heart failure at nutritional risk who might benefit from nutritional support,” Dr. Dr. Gottlieb wrote.
“ ‘Good medical care’ dictates that all hospitalized patients deserve to have a standardized nutritional assessment; the challenge remains: how to determine which patient with heart failure at nutritional risk will benefit by medical nutrition therapy,” Dr. Gottlieb said.
The Swiss National Science Foundation and the Research Council of the Kantonsspital Aarau provided funding for the trial. Dr. Schuetz’s institution has previously received unrestricted grant money unrelated to this project from Nestle Health Science and Abbott Nutrition. Dr. Gottlieb owns a federal trademark for the “Greens, Beans, and Leans” diet, and has a pending federal trademark for “FLOATS”: flax + oats cereal.
A version of this article first appeared on Medscape.com.
Personalized nutritional support for adults hospitalized with chronic heart failure and deemed to be at high nutritional risk reduced the risk of death or adverse cardiovascular events, compared with standard hospital food, new research indicates.
The Swiss EFFORT trial focused on patients with chronic heart failure and high risk of malnutrition defined by low body mass index, weight loss, and low food intake upon hospital admission.
“This high-risk group of chronic heart failure patients showed a significant improvement in mortality over 30 and 180 days, as well as other clinical outcomes, when individualized nutritional support interventions were offered to patients,” Philipp Schuetz, MD, MPH, Kantonsspital Aarau, Switzerland, said in an interview.
“While monitoring the nutritional status should be done also in outpatient settings by [general practitioners], malnutrition screening upon hospital admission may help to identify high-risk patients with high risk for nutritional status deterioration during the hospital stay who will benefit from nutritional assessment and treatment,” said Dr. Schuetz.
The study was published online May 3 in the Journal of the American College of Cardiology.
It’s not all about salt
The findings are based on a prespecified secondary analysis of outcomes in 645 patients (median age, 78.8 years, 52% men) hospitalized with chronic heart failure who participated in the open-label EFFORT study.
One-third of patients were hospitalized for acute decompensated heart failure and two-thirds had chronic heart failure and other acute medical illnesses requiring hospitalization.
All patients were at risk of malnutrition based on a Nutritional Risk Screening (NRS) score of 3 points or higher. They were randomly allocated 1:1 to individualized nutritional support to reach energy, protein, and micronutrient goals or usual hospital food (control group).
By 30 days, 27 of 321 patients (8.4%) receiving nutritional support had died compared with 48 of 324 patients (14.8%) in the control group (adjusted odds ratio [OR]: 0.44; 95% confidence interval, 0.26-0.75; P = .002)
Patients with high nutritional risk (NRS >4 points) showed the most benefit from nutritional support.
Compared with patients with moderate nutritional risk scores (NRS score 3-4), those with high nutritional risk (NRS >4) had a highly significant 65% increased mortality risk over 180 days.
The individual component of the NRS with the strongest association with mortality was low food intake in the week before hospitalization.
Patients who received nutritional support in the hospital also had a lower risk for major cardiovascular events at 30 days (17.4% vs. 26.9%; OR, 0.50; 95% CI, 0.34-0.75; P = .001).
“Historically, cardiologists and internists caring for patients with heart failure have mainly focused on salt-restrictive diets to reduce blood volume and thus optimize heart function. Yet, reduction of salt intake has not been shown to effectively improve clinical outcome but may, on the contrary, increase the risk of malnutrition as low-salt diets are often not tasty,” Dr. Schuetz said.
“Our data suggest that we should move our focus away from salt-restrictive diets to high-protein diets to cover individual nutritional goals in this high-risk group of patients, which includes screening, assessment, and nutritional support by dietitians,” Dr. Schuetz said.
In a linked editorial, Sheldon Gottlieb, MD, Johns Hopkins University, Baltimore, said there has been “relatively little attention” paid to the role of diet in heart failure other than recommending reduced salt intake.
In fact, in the 2021 American College of Cardiology expert consensus recommendations for optimizing heart failure treatment, roughly five words are devoted to diet and exercise and there is no mention of nutrition assessment by a dietitian, he points out.
“This study adds another tile to the still-fragmentary mosaic picture of the patient with heart failure at nutritional risk who might benefit from nutritional support,” Dr. Dr. Gottlieb wrote.
“ ‘Good medical care’ dictates that all hospitalized patients deserve to have a standardized nutritional assessment; the challenge remains: how to determine which patient with heart failure at nutritional risk will benefit by medical nutrition therapy,” Dr. Gottlieb said.
The Swiss National Science Foundation and the Research Council of the Kantonsspital Aarau provided funding for the trial. Dr. Schuetz’s institution has previously received unrestricted grant money unrelated to this project from Nestle Health Science and Abbott Nutrition. Dr. Gottlieb owns a federal trademark for the “Greens, Beans, and Leans” diet, and has a pending federal trademark for “FLOATS”: flax + oats cereal.
A version of this article first appeared on Medscape.com.
Who can call themselves ‘doctor’? The debate heats up
Who Should Get to Be Called ‘Doctor’? shows. The topic has clearly struck a nerve, since a record number of respondents – over 12,000 – voted in the poll.
Most physicians think it’s appropriate for people with other doctorate degrees such as a PhD or EdD to call themselves ‘doctor,’ although slightly more than half said it depends on the context.
The controversy over who gets to be called a doctor was reignited when a Wall Street Journal opinion piece criticized First Lady Jill Biden, EdD, for wanting to be called “Dr Biden.” The piece also challenged the idea that having a PhD is worth the honorific of ‘doctor.’
Medical ethicist Arthur Caplan, PhD, disagreed with that viewpoint, saying the context matters. For example, he prefers to be called “professor” when he’s introduced to the public rather than “doctor” to avoid any confusion about his professional status.
More than 12,000 clinicians including physicians, medical students, nurses, pharmacists, and other health care professionals responded to the poll. The non-MD clinicians were the most likely to say it was always appropriate to be called “doctor” while physicians were the least likely.
Context matters
Large percentages of clinicians – 54% of doctors, 62% of medical students, and 41% of nurses – said that the context matters for being called “doctor.’’
“I earned my PhD in 1995 and my MD in 2000. I think it is contextual. In a research or University setting, “Dr.” seems appropriate for a PhD. That same person in public should probably not hold themselves out as “Dr.” So, maybe MDs and DOs can choose, while others maintain the title in their specific setting.”
Some readers proposed that people with MDs call themselves physicians rather than doctors. Said one: “Anyone with a terminal doctorate degree has the right to use the word doctor. As a physician when someone asks what I do, I say: ‘I am a physician.’ Problem solved. There can only be one physician but there are many types of doctors.”
Physicians and nurses differed most in their views. Just 24% of physicians said it was always appropriate for people with other doctorate degrees to call themselves doctor whereas about an equal number (22%) thought it was never appropriate.
In contrast, 43% of nurses (including advance practice nurses) said it was always appropriate for people with non-MD doctorates to be called doctor. Only 16% said it’s never appropriate.
This difference may reflect the growing number of nurses with doctorate degrees, either a DNP or PhD, who want to be called doctor in clinical settings.
Age made a difference too. Only 16% of physicians younger than age 45 said it was always appropriate for people with non-MD doctorate degrees to be called doctor, compared with 27% of physicians aged 45 and up.
Medical students (31%) were also more likely than physicians to say it was always appropriate for non-MD doctorates to use the title “doctor” and 64% said it depends on the context. This was noteworthy because twice as many medical students as physicians (16% vs. 8%) said they work in academia, research, or military government settings.
Too many ‘doctors’ confuse the public
Physicians (70%) were also more likely to say it was always or often confusing for the public to hear someone without a medical degree addressed as “doctor.” Only 6% of physicians thought it was never or rarely confusing.
Nurses disagreed. Just 45% said that it was always or often confusing while 16% said it was never or rarely confusing.
Medical students were more aligned with physicians on this issue – 60% said it was always or often confusing to the public and just 10% said it was never or rarely confusing.
One reader commented, “The problem is the confusion the ‘doctor’ title causes for patients, especially in a hospital setting. Is the ‘doctor’ a physician, a pharmacist, a psychologist, a nurse, etc., etc.? We need to think not of our own egos but if and how the confusion about this plethora of titles may be hindering good patient care.”
These concerns are not unfounded. The American Medical Association reported in its Truth in Advertising campaign that “patients mistake physicians with nonphysician providers” based on an online survey of 802 adults in 2018. The participants thought these specialists were MDs: dentists (61%), podiatrists (67%), optometrists (47%), psychologists (43%), doctors of nursing (39%), and chiropractors (27%).
The AMA has advocated that states pass the “Health Care Professional Transparency Act,” which New Jersey has enacted. The law requires all health care professionals dealing with patients to wear a name tag that clearly identifies their licensure. Health care professionals must also display their education, training, and licensure in their office.
A version of this article first appeared on Medscape.com.
Who Should Get to Be Called ‘Doctor’? shows. The topic has clearly struck a nerve, since a record number of respondents – over 12,000 – voted in the poll.
Most physicians think it’s appropriate for people with other doctorate degrees such as a PhD or EdD to call themselves ‘doctor,’ although slightly more than half said it depends on the context.
The controversy over who gets to be called a doctor was reignited when a Wall Street Journal opinion piece criticized First Lady Jill Biden, EdD, for wanting to be called “Dr Biden.” The piece also challenged the idea that having a PhD is worth the honorific of ‘doctor.’
Medical ethicist Arthur Caplan, PhD, disagreed with that viewpoint, saying the context matters. For example, he prefers to be called “professor” when he’s introduced to the public rather than “doctor” to avoid any confusion about his professional status.
More than 12,000 clinicians including physicians, medical students, nurses, pharmacists, and other health care professionals responded to the poll. The non-MD clinicians were the most likely to say it was always appropriate to be called “doctor” while physicians were the least likely.
Context matters
Large percentages of clinicians – 54% of doctors, 62% of medical students, and 41% of nurses – said that the context matters for being called “doctor.’’
“I earned my PhD in 1995 and my MD in 2000. I think it is contextual. In a research or University setting, “Dr.” seems appropriate for a PhD. That same person in public should probably not hold themselves out as “Dr.” So, maybe MDs and DOs can choose, while others maintain the title in their specific setting.”
Some readers proposed that people with MDs call themselves physicians rather than doctors. Said one: “Anyone with a terminal doctorate degree has the right to use the word doctor. As a physician when someone asks what I do, I say: ‘I am a physician.’ Problem solved. There can only be one physician but there are many types of doctors.”
Physicians and nurses differed most in their views. Just 24% of physicians said it was always appropriate for people with other doctorate degrees to call themselves doctor whereas about an equal number (22%) thought it was never appropriate.
In contrast, 43% of nurses (including advance practice nurses) said it was always appropriate for people with non-MD doctorates to be called doctor. Only 16% said it’s never appropriate.
This difference may reflect the growing number of nurses with doctorate degrees, either a DNP or PhD, who want to be called doctor in clinical settings.
Age made a difference too. Only 16% of physicians younger than age 45 said it was always appropriate for people with non-MD doctorate degrees to be called doctor, compared with 27% of physicians aged 45 and up.
Medical students (31%) were also more likely than physicians to say it was always appropriate for non-MD doctorates to use the title “doctor” and 64% said it depends on the context. This was noteworthy because twice as many medical students as physicians (16% vs. 8%) said they work in academia, research, or military government settings.
Too many ‘doctors’ confuse the public
Physicians (70%) were also more likely to say it was always or often confusing for the public to hear someone without a medical degree addressed as “doctor.” Only 6% of physicians thought it was never or rarely confusing.
Nurses disagreed. Just 45% said that it was always or often confusing while 16% said it was never or rarely confusing.
Medical students were more aligned with physicians on this issue – 60% said it was always or often confusing to the public and just 10% said it was never or rarely confusing.
One reader commented, “The problem is the confusion the ‘doctor’ title causes for patients, especially in a hospital setting. Is the ‘doctor’ a physician, a pharmacist, a psychologist, a nurse, etc., etc.? We need to think not of our own egos but if and how the confusion about this plethora of titles may be hindering good patient care.”
These concerns are not unfounded. The American Medical Association reported in its Truth in Advertising campaign that “patients mistake physicians with nonphysician providers” based on an online survey of 802 adults in 2018. The participants thought these specialists were MDs: dentists (61%), podiatrists (67%), optometrists (47%), psychologists (43%), doctors of nursing (39%), and chiropractors (27%).
The AMA has advocated that states pass the “Health Care Professional Transparency Act,” which New Jersey has enacted. The law requires all health care professionals dealing with patients to wear a name tag that clearly identifies their licensure. Health care professionals must also display their education, training, and licensure in their office.
A version of this article first appeared on Medscape.com.
Who Should Get to Be Called ‘Doctor’? shows. The topic has clearly struck a nerve, since a record number of respondents – over 12,000 – voted in the poll.
Most physicians think it’s appropriate for people with other doctorate degrees such as a PhD or EdD to call themselves ‘doctor,’ although slightly more than half said it depends on the context.
The controversy over who gets to be called a doctor was reignited when a Wall Street Journal opinion piece criticized First Lady Jill Biden, EdD, for wanting to be called “Dr Biden.” The piece also challenged the idea that having a PhD is worth the honorific of ‘doctor.’
Medical ethicist Arthur Caplan, PhD, disagreed with that viewpoint, saying the context matters. For example, he prefers to be called “professor” when he’s introduced to the public rather than “doctor” to avoid any confusion about his professional status.
More than 12,000 clinicians including physicians, medical students, nurses, pharmacists, and other health care professionals responded to the poll. The non-MD clinicians were the most likely to say it was always appropriate to be called “doctor” while physicians were the least likely.
Context matters
Large percentages of clinicians – 54% of doctors, 62% of medical students, and 41% of nurses – said that the context matters for being called “doctor.’’
“I earned my PhD in 1995 and my MD in 2000. I think it is contextual. In a research or University setting, “Dr.” seems appropriate for a PhD. That same person in public should probably not hold themselves out as “Dr.” So, maybe MDs and DOs can choose, while others maintain the title in their specific setting.”
Some readers proposed that people with MDs call themselves physicians rather than doctors. Said one: “Anyone with a terminal doctorate degree has the right to use the word doctor. As a physician when someone asks what I do, I say: ‘I am a physician.’ Problem solved. There can only be one physician but there are many types of doctors.”
Physicians and nurses differed most in their views. Just 24% of physicians said it was always appropriate for people with other doctorate degrees to call themselves doctor whereas about an equal number (22%) thought it was never appropriate.
In contrast, 43% of nurses (including advance practice nurses) said it was always appropriate for people with non-MD doctorates to be called doctor. Only 16% said it’s never appropriate.
This difference may reflect the growing number of nurses with doctorate degrees, either a DNP or PhD, who want to be called doctor in clinical settings.
Age made a difference too. Only 16% of physicians younger than age 45 said it was always appropriate for people with non-MD doctorate degrees to be called doctor, compared with 27% of physicians aged 45 and up.
Medical students (31%) were also more likely than physicians to say it was always appropriate for non-MD doctorates to use the title “doctor” and 64% said it depends on the context. This was noteworthy because twice as many medical students as physicians (16% vs. 8%) said they work in academia, research, or military government settings.
Too many ‘doctors’ confuse the public
Physicians (70%) were also more likely to say it was always or often confusing for the public to hear someone without a medical degree addressed as “doctor.” Only 6% of physicians thought it was never or rarely confusing.
Nurses disagreed. Just 45% said that it was always or often confusing while 16% said it was never or rarely confusing.
Medical students were more aligned with physicians on this issue – 60% said it was always or often confusing to the public and just 10% said it was never or rarely confusing.
One reader commented, “The problem is the confusion the ‘doctor’ title causes for patients, especially in a hospital setting. Is the ‘doctor’ a physician, a pharmacist, a psychologist, a nurse, etc., etc.? We need to think not of our own egos but if and how the confusion about this plethora of titles may be hindering good patient care.”
These concerns are not unfounded. The American Medical Association reported in its Truth in Advertising campaign that “patients mistake physicians with nonphysician providers” based on an online survey of 802 adults in 2018. The participants thought these specialists were MDs: dentists (61%), podiatrists (67%), optometrists (47%), psychologists (43%), doctors of nursing (39%), and chiropractors (27%).
The AMA has advocated that states pass the “Health Care Professional Transparency Act,” which New Jersey has enacted. The law requires all health care professionals dealing with patients to wear a name tag that clearly identifies their licensure. Health care professionals must also display their education, training, and licensure in their office.
A version of this article first appeared on Medscape.com.
Moderna announces first data showing efficacy of COVID-19 vaccine booster in development
among people already vaccinated for COVID-19, according to first results released May 5.
Furthermore, data from the company’s ongoing phase 2 study show the variant-specific booster, known as mRNA-1273.351, achieved higher antibody titers against the B.1.351 variant than did a booster with the original Moderna vaccine.
“We are encouraged by these new data, which reinforce our confidence that our booster strategy should be protective against these newly detected variants. The strong and rapid boost in titers to levels above primary vaccination also clearly demonstrates the ability of mRNA-1273 to induce immune memory,” Stéphane Bancel, chief executive officer of Moderna, said in a statement.
The phase 2 study researchers also are evaluating a multivariant booster that is a 50/50 mix of mRNA-1273.351 and mRNA-1273, the initial vaccine given Food and Drug Administration emergency use authorization, in a single vial.
Unlike the two-dose regimen with the original vaccine, the boosters are administered as a single dose immunization.
The trial participants received a booster 6-8 months after primary vaccination. Titers to the wild-type SARS-CoV-2 virus remained high and detectable in 37 out of 40 participants. However, prior to the booster, titers against the two variants of concern, B.1.351 and P.1, were lower, with about half of participants showing undetectable levels.
In contrast, 2 weeks after a booster with the original vaccine or the B.1.351 strain-specific product, pseudovirus neutralizing titers were boosted in all participants and all variants tested.
“Following [the] boost, geometric mean titers against the wild-type, B.1.351, and P.1 variants increased to levels similar to or higher than the previously reported peak titers against the ancestral (D614G) strain following primary vaccination,” the company stated.
Both mRNA-1273.351 and mRNA-1273 booster doses were generally well tolerated, the company reported. Safety and tolerability were generally comparable to those reported after the second dose of the original vaccine. Most adverse events were mild to moderate, with injection site pain most common in both groups. Participants also reported fatigue, headache, myalgia, and arthralgia.
The company plans to release data shortly on the booster efficacy at additional time points beyond 2 weeks for mRNA-1273.351, a lower-dose booster with mRNA-1272/351, as well as data on the multivariant mRNA vaccine booster.
In addition to the company’s phase 2 study, the National Institute of Allergy and Infectious Diseases is conducting a separate phase 1 study of mRNA-1273.351.
A version of this article first appeared on Medscape.com.
among people already vaccinated for COVID-19, according to first results released May 5.
Furthermore, data from the company’s ongoing phase 2 study show the variant-specific booster, known as mRNA-1273.351, achieved higher antibody titers against the B.1.351 variant than did a booster with the original Moderna vaccine.
“We are encouraged by these new data, which reinforce our confidence that our booster strategy should be protective against these newly detected variants. The strong and rapid boost in titers to levels above primary vaccination also clearly demonstrates the ability of mRNA-1273 to induce immune memory,” Stéphane Bancel, chief executive officer of Moderna, said in a statement.
The phase 2 study researchers also are evaluating a multivariant booster that is a 50/50 mix of mRNA-1273.351 and mRNA-1273, the initial vaccine given Food and Drug Administration emergency use authorization, in a single vial.
Unlike the two-dose regimen with the original vaccine, the boosters are administered as a single dose immunization.
The trial participants received a booster 6-8 months after primary vaccination. Titers to the wild-type SARS-CoV-2 virus remained high and detectable in 37 out of 40 participants. However, prior to the booster, titers against the two variants of concern, B.1.351 and P.1, were lower, with about half of participants showing undetectable levels.
In contrast, 2 weeks after a booster with the original vaccine or the B.1.351 strain-specific product, pseudovirus neutralizing titers were boosted in all participants and all variants tested.
“Following [the] boost, geometric mean titers against the wild-type, B.1.351, and P.1 variants increased to levels similar to or higher than the previously reported peak titers against the ancestral (D614G) strain following primary vaccination,” the company stated.
Both mRNA-1273.351 and mRNA-1273 booster doses were generally well tolerated, the company reported. Safety and tolerability were generally comparable to those reported after the second dose of the original vaccine. Most adverse events were mild to moderate, with injection site pain most common in both groups. Participants also reported fatigue, headache, myalgia, and arthralgia.
The company plans to release data shortly on the booster efficacy at additional time points beyond 2 weeks for mRNA-1273.351, a lower-dose booster with mRNA-1272/351, as well as data on the multivariant mRNA vaccine booster.
In addition to the company’s phase 2 study, the National Institute of Allergy and Infectious Diseases is conducting a separate phase 1 study of mRNA-1273.351.
A version of this article first appeared on Medscape.com.
among people already vaccinated for COVID-19, according to first results released May 5.
Furthermore, data from the company’s ongoing phase 2 study show the variant-specific booster, known as mRNA-1273.351, achieved higher antibody titers against the B.1.351 variant than did a booster with the original Moderna vaccine.
“We are encouraged by these new data, which reinforce our confidence that our booster strategy should be protective against these newly detected variants. The strong and rapid boost in titers to levels above primary vaccination also clearly demonstrates the ability of mRNA-1273 to induce immune memory,” Stéphane Bancel, chief executive officer of Moderna, said in a statement.
The phase 2 study researchers also are evaluating a multivariant booster that is a 50/50 mix of mRNA-1273.351 and mRNA-1273, the initial vaccine given Food and Drug Administration emergency use authorization, in a single vial.
Unlike the two-dose regimen with the original vaccine, the boosters are administered as a single dose immunization.
The trial participants received a booster 6-8 months after primary vaccination. Titers to the wild-type SARS-CoV-2 virus remained high and detectable in 37 out of 40 participants. However, prior to the booster, titers against the two variants of concern, B.1.351 and P.1, were lower, with about half of participants showing undetectable levels.
In contrast, 2 weeks after a booster with the original vaccine or the B.1.351 strain-specific product, pseudovirus neutralizing titers were boosted in all participants and all variants tested.
“Following [the] boost, geometric mean titers against the wild-type, B.1.351, and P.1 variants increased to levels similar to or higher than the previously reported peak titers against the ancestral (D614G) strain following primary vaccination,” the company stated.
Both mRNA-1273.351 and mRNA-1273 booster doses were generally well tolerated, the company reported. Safety and tolerability were generally comparable to those reported after the second dose of the original vaccine. Most adverse events were mild to moderate, with injection site pain most common in both groups. Participants also reported fatigue, headache, myalgia, and arthralgia.
The company plans to release data shortly on the booster efficacy at additional time points beyond 2 weeks for mRNA-1273.351, a lower-dose booster with mRNA-1272/351, as well as data on the multivariant mRNA vaccine booster.
In addition to the company’s phase 2 study, the National Institute of Allergy and Infectious Diseases is conducting a separate phase 1 study of mRNA-1273.351.
A version of this article first appeared on Medscape.com.
Hypertension worsened by commonly used prescription meds
Nearly half of these American adults had hypertension, and in this subgroup, 18.5% reported using a prescription drug known to increase blood pressure. The most widely used class of agents with this effect was antidepressants, used by 8.7%; followed by nonsteroidal anti-inflammatory drugs (NSAIDs), used by 6.5%; steroids, 1.9%; estrogens, 1.7%; and several other agents each used by fewer than 1% of the study cohort, John Vitarello, MD, said during a press briefing on reports from the upcoming annual scientific sessions of the American College of Cardiology.
He and his associates estimated that this use of prescription drugs known to raise blood pressure could be what stands in the way of some 560,000-2.2 million Americans from having their hypertension under control, depending on the exact blood pressure impact that various pressure-increasing drugs have and presuming that half of those on blood pressure increasing agents could stop them and switch to alternative agents, said Dr. Vitarello, a researcher at Beth Israel Deaconess Medical Center in Boston.
He also highlighted that the study assessed only prescription drugs and did not examine OTC drug use, which may be especially relevant for the many people who regularly take NSAIDs.
“Clinicians should review the prescription and OTC drug use of patients with hypertension and consider stopping drugs that increase blood pressure or switching the patient to alternatives” that are blood pressure neutral, Dr. Vitarello said during the briefing. He cautioned that maintaining hypertensive patients on agents that raise their blood pressure can result in “prescribing cascades” where taking drugs that boost blood pressure results in need for intensified antihypertensive treatment.
An opportunity for NSAID alternatives
“This study hopefully raises awareness that there is a very high use of medications that increase blood pressure, and use of OTC agents could increase the rate even higher” said Eugene Yang, MD, a cardiologist and codirector of the Cardiovascular Wellness and Prevention Program of the University of Washington, Seattle. Substituting for certain antidepressant agents may often not be realistic, but an opportunity exists for reducing NSAID use, a class also linked with an increased risk for bleeding and other adverse effects, Dr. Yang said during the briefing. Minimizing use of NSAIDs including ibuprofen and naproxen use “is something to think about,” he suggested.
“The effect of NSAIDs on blood pressure is not well studied and can vary from person to person” noted Dr. Vitarello, who added that higher NSAID dosages and more prolonged use likely increase the risk for an adverse effect on blood pressure. One reasonable option is to encourage patients to use an alternative class of pain reliever such as acetaminophen.
It remains “a challenge” to discern differences in adverse blood pressure effects, and in all adverse cardiovascular effects among different NSAIDs, said Dr. Yang. Results from “some studies show that certain NSAIDs may be safer, but other studies did not. We need to be very careful using NSAIDs because, on average, they increase blood pressure by about 3 mm Hg. We need to be mindful to try to prescribe alternative agents, like acetaminophen.”
A decade of data from NHANES
The analysis run by Dr. Vitarello and associates used data from 27,599 American adults included in the NHANES during 2009-2018, and focused on the 44% who either had an average blood pressure measurement of at least 130/80 mm Hg or reported having ever been told by a clinician that they had hypertension. The NHANES assessments included the prescription medications taken by each participant. The prevalence of using at least one prescription drug known to raise blood pressure was 24% among women and 14% among men, and 4% of those with hypertension were on two or more pressure-increasing agents.
The researchers based their identification of pressure-increasing prescription drugs on the list included in the 2017 guideline for managing high blood pressure from the American College of Cardiology and American Heart Association. This list specifies that the antidepressants that raise blood pressure are the monoamine oxidase inhibitors, serotonin norepinephrine reuptake inhibitors, and tricyclic antidepressants.
Dr. Vitarello and Dr. Yang had no disclosures.
Nearly half of these American adults had hypertension, and in this subgroup, 18.5% reported using a prescription drug known to increase blood pressure. The most widely used class of agents with this effect was antidepressants, used by 8.7%; followed by nonsteroidal anti-inflammatory drugs (NSAIDs), used by 6.5%; steroids, 1.9%; estrogens, 1.7%; and several other agents each used by fewer than 1% of the study cohort, John Vitarello, MD, said during a press briefing on reports from the upcoming annual scientific sessions of the American College of Cardiology.
He and his associates estimated that this use of prescription drugs known to raise blood pressure could be what stands in the way of some 560,000-2.2 million Americans from having their hypertension under control, depending on the exact blood pressure impact that various pressure-increasing drugs have and presuming that half of those on blood pressure increasing agents could stop them and switch to alternative agents, said Dr. Vitarello, a researcher at Beth Israel Deaconess Medical Center in Boston.
He also highlighted that the study assessed only prescription drugs and did not examine OTC drug use, which may be especially relevant for the many people who regularly take NSAIDs.
“Clinicians should review the prescription and OTC drug use of patients with hypertension and consider stopping drugs that increase blood pressure or switching the patient to alternatives” that are blood pressure neutral, Dr. Vitarello said during the briefing. He cautioned that maintaining hypertensive patients on agents that raise their blood pressure can result in “prescribing cascades” where taking drugs that boost blood pressure results in need for intensified antihypertensive treatment.
An opportunity for NSAID alternatives
“This study hopefully raises awareness that there is a very high use of medications that increase blood pressure, and use of OTC agents could increase the rate even higher” said Eugene Yang, MD, a cardiologist and codirector of the Cardiovascular Wellness and Prevention Program of the University of Washington, Seattle. Substituting for certain antidepressant agents may often not be realistic, but an opportunity exists for reducing NSAID use, a class also linked with an increased risk for bleeding and other adverse effects, Dr. Yang said during the briefing. Minimizing use of NSAIDs including ibuprofen and naproxen use “is something to think about,” he suggested.
“The effect of NSAIDs on blood pressure is not well studied and can vary from person to person” noted Dr. Vitarello, who added that higher NSAID dosages and more prolonged use likely increase the risk for an adverse effect on blood pressure. One reasonable option is to encourage patients to use an alternative class of pain reliever such as acetaminophen.
It remains “a challenge” to discern differences in adverse blood pressure effects, and in all adverse cardiovascular effects among different NSAIDs, said Dr. Yang. Results from “some studies show that certain NSAIDs may be safer, but other studies did not. We need to be very careful using NSAIDs because, on average, they increase blood pressure by about 3 mm Hg. We need to be mindful to try to prescribe alternative agents, like acetaminophen.”
A decade of data from NHANES
The analysis run by Dr. Vitarello and associates used data from 27,599 American adults included in the NHANES during 2009-2018, and focused on the 44% who either had an average blood pressure measurement of at least 130/80 mm Hg or reported having ever been told by a clinician that they had hypertension. The NHANES assessments included the prescription medications taken by each participant. The prevalence of using at least one prescription drug known to raise blood pressure was 24% among women and 14% among men, and 4% of those with hypertension were on two or more pressure-increasing agents.
The researchers based their identification of pressure-increasing prescription drugs on the list included in the 2017 guideline for managing high blood pressure from the American College of Cardiology and American Heart Association. This list specifies that the antidepressants that raise blood pressure are the monoamine oxidase inhibitors, serotonin norepinephrine reuptake inhibitors, and tricyclic antidepressants.
Dr. Vitarello and Dr. Yang had no disclosures.
Nearly half of these American adults had hypertension, and in this subgroup, 18.5% reported using a prescription drug known to increase blood pressure. The most widely used class of agents with this effect was antidepressants, used by 8.7%; followed by nonsteroidal anti-inflammatory drugs (NSAIDs), used by 6.5%; steroids, 1.9%; estrogens, 1.7%; and several other agents each used by fewer than 1% of the study cohort, John Vitarello, MD, said during a press briefing on reports from the upcoming annual scientific sessions of the American College of Cardiology.
He and his associates estimated that this use of prescription drugs known to raise blood pressure could be what stands in the way of some 560,000-2.2 million Americans from having their hypertension under control, depending on the exact blood pressure impact that various pressure-increasing drugs have and presuming that half of those on blood pressure increasing agents could stop them and switch to alternative agents, said Dr. Vitarello, a researcher at Beth Israel Deaconess Medical Center in Boston.
He also highlighted that the study assessed only prescription drugs and did not examine OTC drug use, which may be especially relevant for the many people who regularly take NSAIDs.
“Clinicians should review the prescription and OTC drug use of patients with hypertension and consider stopping drugs that increase blood pressure or switching the patient to alternatives” that are blood pressure neutral, Dr. Vitarello said during the briefing. He cautioned that maintaining hypertensive patients on agents that raise their blood pressure can result in “prescribing cascades” where taking drugs that boost blood pressure results in need for intensified antihypertensive treatment.
An opportunity for NSAID alternatives
“This study hopefully raises awareness that there is a very high use of medications that increase blood pressure, and use of OTC agents could increase the rate even higher” said Eugene Yang, MD, a cardiologist and codirector of the Cardiovascular Wellness and Prevention Program of the University of Washington, Seattle. Substituting for certain antidepressant agents may often not be realistic, but an opportunity exists for reducing NSAID use, a class also linked with an increased risk for bleeding and other adverse effects, Dr. Yang said during the briefing. Minimizing use of NSAIDs including ibuprofen and naproxen use “is something to think about,” he suggested.
“The effect of NSAIDs on blood pressure is not well studied and can vary from person to person” noted Dr. Vitarello, who added that higher NSAID dosages and more prolonged use likely increase the risk for an adverse effect on blood pressure. One reasonable option is to encourage patients to use an alternative class of pain reliever such as acetaminophen.
It remains “a challenge” to discern differences in adverse blood pressure effects, and in all adverse cardiovascular effects among different NSAIDs, said Dr. Yang. Results from “some studies show that certain NSAIDs may be safer, but other studies did not. We need to be very careful using NSAIDs because, on average, they increase blood pressure by about 3 mm Hg. We need to be mindful to try to prescribe alternative agents, like acetaminophen.”
A decade of data from NHANES
The analysis run by Dr. Vitarello and associates used data from 27,599 American adults included in the NHANES during 2009-2018, and focused on the 44% who either had an average blood pressure measurement of at least 130/80 mm Hg or reported having ever been told by a clinician that they had hypertension. The NHANES assessments included the prescription medications taken by each participant. The prevalence of using at least one prescription drug known to raise blood pressure was 24% among women and 14% among men, and 4% of those with hypertension were on two or more pressure-increasing agents.
The researchers based their identification of pressure-increasing prescription drugs on the list included in the 2017 guideline for managing high blood pressure from the American College of Cardiology and American Heart Association. This list specifies that the antidepressants that raise blood pressure are the monoamine oxidase inhibitors, serotonin norepinephrine reuptake inhibitors, and tricyclic antidepressants.
Dr. Vitarello and Dr. Yang had no disclosures.
FROM ACC 2021
Exercise plus liraglutide better for maintaining weight loss than either strategy alone
For persons with obesity who lost a substantial amount of weight on a low-calorie diet, the combination of exercise and medication significantly improved weight-loss maintenance, and more so than either strategy alone, according to results of a randomized, head-to-head trial.
A year after starting moderate to vigorous exercise coupled with liraglutide treatment, study participants had a weight loss 9.5 kg more than those who received placebo and usual activity, study results show.
Reductions in both weight and fat loss seen with exercise and liraglutide was roughly twice as much as what was achieved at 1 year with the strategies of liraglutide or exercise alone, according to authors of the study, which appears in the New England Journal of Medicine .
Although the findings may not apply to those who can’t or won’t perform moderate to vigorous exercise, the intervention in this study was nevertheless feasible in this group of persons with obesity who had a very low level of fitness, according to the authors.
Hope for healthy weight loss maintenance
Investigator Signe S. Torekov, PhD, said in an interview that these results provide hope that more-intensive exercise regimens, with or without medication, can be useful and well accepted among individuals struggling with obesity.
“When we started our study, we were told, ‘you are never going to have people with obesity exercising that much, and for that long’ – but people were actually very happy about the exercise,” said Dr. Torekov, a professor in the department of biomedical sciences at the University of Copenhagen.
“If you actually set up a program where people are monitored and you have a feedback system, then exercise is an excellent component in obesity treatment that should be much more actively used – not only for its weight-lowering component, but also for improving health and quality of life,” she said in an interview.
Weight-management specialist John D. Clark, MD, PhD, said results of this study can be used to help inform patients about how successful different strategies incorporating exercise and medication may be following initial weight loss.
“When patients plateau on a consistent, calorie-restricted dietary plan, we can educate them and manage expectations about what options may be available to them after their initial weight loss,” said Dr. Clark, of the University of Texas, Dallas.
“If the patient’s goal specifically is weight loss at all costs, then I may suggest, ‘let’s consider liraglutide or liraglutide in combination with exercise,’ ” he said in an interview. “Exercise improves body composition, even if it may not on its own be as successful in the next phase of their weight-loss journey, as shown in this study.”
Obesity and weight-loss challenges
Although it’s not uncommon for obese patients to lose a large amount of weight, keeping the weight off is frequently a challenge unless the patient follows a structured weight maintenance program, according to Dr. Torekov and coauthors.
The rapid weight regain seen in many obese patients could be a result of reductions in total energy expenditure or increased appetite. Exercise is one strategy to sustain weight loss, though according to the authors, very few studies have looked at exercise in isolation to quantify its contribution to maintenance.
Accordingly, the present study sought to determine whether exercise, medication, or the combination thereof works best to keep weight off.
The study incorporated liraglutide, a GLP-1 receptor agonist indicated for chronic weight management, along with a reduced-calorie diet and increased physical activity, in adults with elevated body mass index and at least one weight-related comorbidity.
The investigator-initiated phase 3 trial included 215 adults with a body mass index of 32-43. Individuals with type 2 diabetes were excluded. All participants followed an 8-week, low-calorie diet comprising 800 calories per day.
Participants who lost 5% or more of their body weight were then randomized to 1 year of exercise plus liraglutide, exercise plus placebo, usual activity plus liraglutide, or usual activity plus placebo.
The exercise program – which was structured but flexible, according to investigators – included group exercise sessions that incorporated 30 minutes of indoor cycling and 15 minutes of circuit training 2 days each week. Participants wore heart rate monitors during exercise to make sure they reached targets for moderate to vigorous intensity.
Instructors trained in exercise physiology planned and monitored individualized exercise programs for each participant in the exercise-medication or exercise-only arms of the study.
Participants in all groups attended 12 one-on-one consultations where body weight was measured and dietetic support was provided.
Weight loss with exercise and medication
Out of 215 individuals enrolled in the study, 195 lost at least 5% of body weight and continued on to the randomized portion, the investigators reported. During the diet phase, they lost a mean of 13.1 kg, translating into a 12% mean reduction in body weight.
The mean frequency of exercise was 2.4 times per week in the exercise-plus-medication group and 2.5 times per week in the exercise-only group. About one-third of the exercise took place in the group sessions, and there was no difference in relative intensity between group and individual exercise regimens, the investigators said.
Individuals in the exercise plus medication group continued to lose more weight, such that, at the end of 1 year, the weight loss decreased even further, by a mean of –3.4 kg. By contrast, weight increased by a mean of 6.1 kg for the placebo group, adding up to a treatment difference of –9.5 kg (95% confidence interval, –13.1 to –5.9; P < .001), according to the report.
That treatment effect was also seen, but more muted, in the exercise- and liraglutide-only groups, at –4.1 kg and –6.8 kg, respectively.
A significant treatment effect was observed for exercise plus liraglutide, compared with exercise alone, at –5.4 kg (P = .004), while the treatment effect for the combination versus liraglutide alone was not significant at –2.7 kg (P = .13), the data show.
Body-fat reduction at 52 weeks was –3.9 percentage points for exercise plus liraglutide as compared with placebo, or roughly twice the reductions seen in the exercise- and liraglutide-alone groups, the investigators said, adding that the combination preserved lean mass.
Reductions in hemoglobin A1c, which are generally thought to reduce diabetes risk, were reduced in both the liraglutide and liraglutide-exercise combination group, according to their report.
The research was supported in part by grants from the Novo Nordisk Foundation.
For persons with obesity who lost a substantial amount of weight on a low-calorie diet, the combination of exercise and medication significantly improved weight-loss maintenance, and more so than either strategy alone, according to results of a randomized, head-to-head trial.
A year after starting moderate to vigorous exercise coupled with liraglutide treatment, study participants had a weight loss 9.5 kg more than those who received placebo and usual activity, study results show.
Reductions in both weight and fat loss seen with exercise and liraglutide was roughly twice as much as what was achieved at 1 year with the strategies of liraglutide or exercise alone, according to authors of the study, which appears in the New England Journal of Medicine .
Although the findings may not apply to those who can’t or won’t perform moderate to vigorous exercise, the intervention in this study was nevertheless feasible in this group of persons with obesity who had a very low level of fitness, according to the authors.
Hope for healthy weight loss maintenance
Investigator Signe S. Torekov, PhD, said in an interview that these results provide hope that more-intensive exercise regimens, with or without medication, can be useful and well accepted among individuals struggling with obesity.
“When we started our study, we were told, ‘you are never going to have people with obesity exercising that much, and for that long’ – but people were actually very happy about the exercise,” said Dr. Torekov, a professor in the department of biomedical sciences at the University of Copenhagen.
“If you actually set up a program where people are monitored and you have a feedback system, then exercise is an excellent component in obesity treatment that should be much more actively used – not only for its weight-lowering component, but also for improving health and quality of life,” she said in an interview.
Weight-management specialist John D. Clark, MD, PhD, said results of this study can be used to help inform patients about how successful different strategies incorporating exercise and medication may be following initial weight loss.
“When patients plateau on a consistent, calorie-restricted dietary plan, we can educate them and manage expectations about what options may be available to them after their initial weight loss,” said Dr. Clark, of the University of Texas, Dallas.
“If the patient’s goal specifically is weight loss at all costs, then I may suggest, ‘let’s consider liraglutide or liraglutide in combination with exercise,’ ” he said in an interview. “Exercise improves body composition, even if it may not on its own be as successful in the next phase of their weight-loss journey, as shown in this study.”
Obesity and weight-loss challenges
Although it’s not uncommon for obese patients to lose a large amount of weight, keeping the weight off is frequently a challenge unless the patient follows a structured weight maintenance program, according to Dr. Torekov and coauthors.
The rapid weight regain seen in many obese patients could be a result of reductions in total energy expenditure or increased appetite. Exercise is one strategy to sustain weight loss, though according to the authors, very few studies have looked at exercise in isolation to quantify its contribution to maintenance.
Accordingly, the present study sought to determine whether exercise, medication, or the combination thereof works best to keep weight off.
The study incorporated liraglutide, a GLP-1 receptor agonist indicated for chronic weight management, along with a reduced-calorie diet and increased physical activity, in adults with elevated body mass index and at least one weight-related comorbidity.
The investigator-initiated phase 3 trial included 215 adults with a body mass index of 32-43. Individuals with type 2 diabetes were excluded. All participants followed an 8-week, low-calorie diet comprising 800 calories per day.
Participants who lost 5% or more of their body weight were then randomized to 1 year of exercise plus liraglutide, exercise plus placebo, usual activity plus liraglutide, or usual activity plus placebo.
The exercise program – which was structured but flexible, according to investigators – included group exercise sessions that incorporated 30 minutes of indoor cycling and 15 minutes of circuit training 2 days each week. Participants wore heart rate monitors during exercise to make sure they reached targets for moderate to vigorous intensity.
Instructors trained in exercise physiology planned and monitored individualized exercise programs for each participant in the exercise-medication or exercise-only arms of the study.
Participants in all groups attended 12 one-on-one consultations where body weight was measured and dietetic support was provided.
Weight loss with exercise and medication
Out of 215 individuals enrolled in the study, 195 lost at least 5% of body weight and continued on to the randomized portion, the investigators reported. During the diet phase, they lost a mean of 13.1 kg, translating into a 12% mean reduction in body weight.
The mean frequency of exercise was 2.4 times per week in the exercise-plus-medication group and 2.5 times per week in the exercise-only group. About one-third of the exercise took place in the group sessions, and there was no difference in relative intensity between group and individual exercise regimens, the investigators said.
Individuals in the exercise plus medication group continued to lose more weight, such that, at the end of 1 year, the weight loss decreased even further, by a mean of –3.4 kg. By contrast, weight increased by a mean of 6.1 kg for the placebo group, adding up to a treatment difference of –9.5 kg (95% confidence interval, –13.1 to –5.9; P < .001), according to the report.
That treatment effect was also seen, but more muted, in the exercise- and liraglutide-only groups, at –4.1 kg and –6.8 kg, respectively.
A significant treatment effect was observed for exercise plus liraglutide, compared with exercise alone, at –5.4 kg (P = .004), while the treatment effect for the combination versus liraglutide alone was not significant at –2.7 kg (P = .13), the data show.
Body-fat reduction at 52 weeks was –3.9 percentage points for exercise plus liraglutide as compared with placebo, or roughly twice the reductions seen in the exercise- and liraglutide-alone groups, the investigators said, adding that the combination preserved lean mass.
Reductions in hemoglobin A1c, which are generally thought to reduce diabetes risk, were reduced in both the liraglutide and liraglutide-exercise combination group, according to their report.
The research was supported in part by grants from the Novo Nordisk Foundation.
For persons with obesity who lost a substantial amount of weight on a low-calorie diet, the combination of exercise and medication significantly improved weight-loss maintenance, and more so than either strategy alone, according to results of a randomized, head-to-head trial.
A year after starting moderate to vigorous exercise coupled with liraglutide treatment, study participants had a weight loss 9.5 kg more than those who received placebo and usual activity, study results show.
Reductions in both weight and fat loss seen with exercise and liraglutide was roughly twice as much as what was achieved at 1 year with the strategies of liraglutide or exercise alone, according to authors of the study, which appears in the New England Journal of Medicine .
Although the findings may not apply to those who can’t or won’t perform moderate to vigorous exercise, the intervention in this study was nevertheless feasible in this group of persons with obesity who had a very low level of fitness, according to the authors.
Hope for healthy weight loss maintenance
Investigator Signe S. Torekov, PhD, said in an interview that these results provide hope that more-intensive exercise regimens, with or without medication, can be useful and well accepted among individuals struggling with obesity.
“When we started our study, we were told, ‘you are never going to have people with obesity exercising that much, and for that long’ – but people were actually very happy about the exercise,” said Dr. Torekov, a professor in the department of biomedical sciences at the University of Copenhagen.
“If you actually set up a program where people are monitored and you have a feedback system, then exercise is an excellent component in obesity treatment that should be much more actively used – not only for its weight-lowering component, but also for improving health and quality of life,” she said in an interview.
Weight-management specialist John D. Clark, MD, PhD, said results of this study can be used to help inform patients about how successful different strategies incorporating exercise and medication may be following initial weight loss.
“When patients plateau on a consistent, calorie-restricted dietary plan, we can educate them and manage expectations about what options may be available to them after their initial weight loss,” said Dr. Clark, of the University of Texas, Dallas.
“If the patient’s goal specifically is weight loss at all costs, then I may suggest, ‘let’s consider liraglutide or liraglutide in combination with exercise,’ ” he said in an interview. “Exercise improves body composition, even if it may not on its own be as successful in the next phase of their weight-loss journey, as shown in this study.”
Obesity and weight-loss challenges
Although it’s not uncommon for obese patients to lose a large amount of weight, keeping the weight off is frequently a challenge unless the patient follows a structured weight maintenance program, according to Dr. Torekov and coauthors.
The rapid weight regain seen in many obese patients could be a result of reductions in total energy expenditure or increased appetite. Exercise is one strategy to sustain weight loss, though according to the authors, very few studies have looked at exercise in isolation to quantify its contribution to maintenance.
Accordingly, the present study sought to determine whether exercise, medication, or the combination thereof works best to keep weight off.
The study incorporated liraglutide, a GLP-1 receptor agonist indicated for chronic weight management, along with a reduced-calorie diet and increased physical activity, in adults with elevated body mass index and at least one weight-related comorbidity.
The investigator-initiated phase 3 trial included 215 adults with a body mass index of 32-43. Individuals with type 2 diabetes were excluded. All participants followed an 8-week, low-calorie diet comprising 800 calories per day.
Participants who lost 5% or more of their body weight were then randomized to 1 year of exercise plus liraglutide, exercise plus placebo, usual activity plus liraglutide, or usual activity plus placebo.
The exercise program – which was structured but flexible, according to investigators – included group exercise sessions that incorporated 30 minutes of indoor cycling and 15 minutes of circuit training 2 days each week. Participants wore heart rate monitors during exercise to make sure they reached targets for moderate to vigorous intensity.
Instructors trained in exercise physiology planned and monitored individualized exercise programs for each participant in the exercise-medication or exercise-only arms of the study.
Participants in all groups attended 12 one-on-one consultations where body weight was measured and dietetic support was provided.
Weight loss with exercise and medication
Out of 215 individuals enrolled in the study, 195 lost at least 5% of body weight and continued on to the randomized portion, the investigators reported. During the diet phase, they lost a mean of 13.1 kg, translating into a 12% mean reduction in body weight.
The mean frequency of exercise was 2.4 times per week in the exercise-plus-medication group and 2.5 times per week in the exercise-only group. About one-third of the exercise took place in the group sessions, and there was no difference in relative intensity between group and individual exercise regimens, the investigators said.
Individuals in the exercise plus medication group continued to lose more weight, such that, at the end of 1 year, the weight loss decreased even further, by a mean of –3.4 kg. By contrast, weight increased by a mean of 6.1 kg for the placebo group, adding up to a treatment difference of –9.5 kg (95% confidence interval, –13.1 to –5.9; P < .001), according to the report.
That treatment effect was also seen, but more muted, in the exercise- and liraglutide-only groups, at –4.1 kg and –6.8 kg, respectively.
A significant treatment effect was observed for exercise plus liraglutide, compared with exercise alone, at –5.4 kg (P = .004), while the treatment effect for the combination versus liraglutide alone was not significant at –2.7 kg (P = .13), the data show.
Body-fat reduction at 52 weeks was –3.9 percentage points for exercise plus liraglutide as compared with placebo, or roughly twice the reductions seen in the exercise- and liraglutide-alone groups, the investigators said, adding that the combination preserved lean mass.
Reductions in hemoglobin A1c, which are generally thought to reduce diabetes risk, were reduced in both the liraglutide and liraglutide-exercise combination group, according to their report.
The research was supported in part by grants from the Novo Nordisk Foundation.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE