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FIRE a win for physiology-guided MI complete revascularization in older patients
(MVD) in a large, randomized trial.
In the study with more than 1,400 patients, CR was guided by assessments of the functional effect of coronary lesions other than the MI culprit, a process that selects or excludes the lesions, regardless of angiographic profile, as targets for percutaneous coronary intervention (PCI).
Such physiology-guided CR led to a significant 27% drop in risk for a composite primary endpoint over 1 year in the trial, called FIRE (Functional Assessment in Elderly MI Patients with Multivessel Disease), compared with the culprit-only approach. The endpoint included death, MI, stroke, or ischemia-driven revascularization.
Risk for cardiovascular (CV) death or MI fell by 36% in the trial, and all-cause mortality declined 30%. The differences were significant, although the study wasn’t powered for those secondary endpoints. Safety outcomes were similar for the two revascularization approaches.
FIRE was noteworthy for entering only patients with ST-segment elevation or non–ST-segment elevation MI (STEMI or NSTEMI) who were age 75 years or older, a higher-risk age group poorly represented in earlier CR trials. Such patients in practice are usually managed with the culprit lesion–only approach because of a lack of good evidence supporting CR, observed Simone Biscaglia, MD, the study’s principal investigator.
“This is the first trial actually showing a benefit” from physiology-guided CR in older patients with acute MI that is similar to what the strategy can offer younger patients, said Dr. Biscaglia, from Azienda Ospedaliera Universitaria S. Anna, Ferrara, Italy.
Biscaglia made the comments at a media briefing on FIRE held during the annual congress of the European Society of Cardiology, where he presented the study. He is also lead author on its publication in the New England Journal of Medicine.
“This is a remarkable trial that adds substantially to prior studies that examined the topic of complete versus culprit-only revascularization,” Deepak L. Bhatt, MD, MPH, Icahn School of Medicine at Mount Sinai, New York, said in an interview.
It shows “quite clearly” that physiology-guided CR is superior to the culprit-only approach in patients with acute MI, said Dr. Bhatt, who is also director of Mount Sinai Heart at Mount Sinai Hospital and not connected to FIRE.
The primary findings applied to a range of different patient subgroups, including those older than 80. That’s important, he said, because “it is sometimes incorrectly assumed that patients who are older may not benefit from complete revascularization in this setting.”
And the trial’s finding of reduced risk for CV death or MI in the CR group “really should make the complete revascularization approach the standard of care in MI patients without contraindications,” Dr. Bhatt said. And certainly, “age per se should no longer be considered a contraindication.”
“First and foremost, the FIRE trial confirms the benefit of complete revascularization that has been observed in previous trials and provides additional evidence for this approach in older patients,” wrote the author of an editorial accompanying the published report.
The mortality reduction with CR at 1 years “is particularly notable” and underscores that CR should be considered in all patients with acute MI, “regardless of age,” wrote Shamir R. Mehta, MD, McMaster University, Hamilton, Ont., and Hamilton Health Sciences.
Dr. Mehta was principal investigator for the 2019 COMPLETE trial, which made the case for CR, guided by standard angiography, in patients with MVD and STEMI; their age averaged about 62 years.
FIRE definitely ought to sway practice toward greater use of physiology-guided CR regardless of age, observed Vijay Kunadian, MBBS, MD, invited discussant for the Biscaglia presentation. “My oldest patient is 98,” she said, “and it is beneficial without a doubt.”
But Dr. Kunadian, from Newcastle (England) University, said that the trial results can’t be generalized to all older patients. That’s because their outcomes after CR could vary depending on, for example, their different frailties or comorbidities, cognition, or CV history. “So, there is an absolute need to individualize care.”
FIRE enrolled patients 75 years or older with MVD, about 64% male, who had been admitted with acute STEMI or NSTEMI at 34 sites in Italy, Spain, and Poland. All underwent successful culprit-lesion PCI using, as “strongly” recommended, the same model of sirolimus-eluting stent.
Patients were randomly assigned to physiology-guided CR of nonculprit lesions, at the same session or at least during the same hospitalization, or to no further revascularization: 720 and 725 patients, respectively.
The hazard ratio for the composite primary outcome, CR versus culprit-only PCI was 0.73 (95% confidence interval, 0.57-0.93; P = .01). The benefit was driven by reductions in three individual components of the primary endpoint: death, MI, and revascularization, but not stroke.
The HR for CV death or MI was 0.64 (95% CI, 0.47-0.88) and for death from any cause was 0.70 (95% CI, 0.51-0.96).
There was no significant difference in the primary safety outcome, a composite of contrast-related acute kidney injury, stroke, or Bleeding Academic Research Consortium grade 3 to 5 bleeding at 1 year. The rates were 22.5% in those assigned to CR and 20.4% in the culprit-only group.
The functional effect of individual lesions was assessed by either of two methods, crossing them with a standard “pressure wire” or by angiographic derivation of their quantitative flow ratio.
The choice was “left to operator discretion,” Dr. Biscaglia said in an interview, “because we wanted to mirror clinical practice at the participating centers.” Still, the CR primary benefit was independent of the physiology-guidance method.
FIRE’s sponsor – the nonprofit Consorzio Futuro in Ricerca, Italy – received grant support from Sahajanand Medical Technologies, Medis Medical Imaging systems, Eukon, Siemens Healthineers, General Electric Healthcare, and Insight Lifetech. Dr. Biscaglia had no other disclosures. Dr. Mehta reported receiving grants from Abbott Vascular and personal fees from Amgen, Janssen, and Bristol Myers Squibb. Dr. Bhatt reported numerous disclosures with various companies and organizations. Dr. Kunadian had no disclosures.
A version of this article first appeared on Medscape.com.
(MVD) in a large, randomized trial.
In the study with more than 1,400 patients, CR was guided by assessments of the functional effect of coronary lesions other than the MI culprit, a process that selects or excludes the lesions, regardless of angiographic profile, as targets for percutaneous coronary intervention (PCI).
Such physiology-guided CR led to a significant 27% drop in risk for a composite primary endpoint over 1 year in the trial, called FIRE (Functional Assessment in Elderly MI Patients with Multivessel Disease), compared with the culprit-only approach. The endpoint included death, MI, stroke, or ischemia-driven revascularization.
Risk for cardiovascular (CV) death or MI fell by 36% in the trial, and all-cause mortality declined 30%. The differences were significant, although the study wasn’t powered for those secondary endpoints. Safety outcomes were similar for the two revascularization approaches.
FIRE was noteworthy for entering only patients with ST-segment elevation or non–ST-segment elevation MI (STEMI or NSTEMI) who were age 75 years or older, a higher-risk age group poorly represented in earlier CR trials. Such patients in practice are usually managed with the culprit lesion–only approach because of a lack of good evidence supporting CR, observed Simone Biscaglia, MD, the study’s principal investigator.
“This is the first trial actually showing a benefit” from physiology-guided CR in older patients with acute MI that is similar to what the strategy can offer younger patients, said Dr. Biscaglia, from Azienda Ospedaliera Universitaria S. Anna, Ferrara, Italy.
Biscaglia made the comments at a media briefing on FIRE held during the annual congress of the European Society of Cardiology, where he presented the study. He is also lead author on its publication in the New England Journal of Medicine.
“This is a remarkable trial that adds substantially to prior studies that examined the topic of complete versus culprit-only revascularization,” Deepak L. Bhatt, MD, MPH, Icahn School of Medicine at Mount Sinai, New York, said in an interview.
It shows “quite clearly” that physiology-guided CR is superior to the culprit-only approach in patients with acute MI, said Dr. Bhatt, who is also director of Mount Sinai Heart at Mount Sinai Hospital and not connected to FIRE.
The primary findings applied to a range of different patient subgroups, including those older than 80. That’s important, he said, because “it is sometimes incorrectly assumed that patients who are older may not benefit from complete revascularization in this setting.”
And the trial’s finding of reduced risk for CV death or MI in the CR group “really should make the complete revascularization approach the standard of care in MI patients without contraindications,” Dr. Bhatt said. And certainly, “age per se should no longer be considered a contraindication.”
“First and foremost, the FIRE trial confirms the benefit of complete revascularization that has been observed in previous trials and provides additional evidence for this approach in older patients,” wrote the author of an editorial accompanying the published report.
The mortality reduction with CR at 1 years “is particularly notable” and underscores that CR should be considered in all patients with acute MI, “regardless of age,” wrote Shamir R. Mehta, MD, McMaster University, Hamilton, Ont., and Hamilton Health Sciences.
Dr. Mehta was principal investigator for the 2019 COMPLETE trial, which made the case for CR, guided by standard angiography, in patients with MVD and STEMI; their age averaged about 62 years.
FIRE definitely ought to sway practice toward greater use of physiology-guided CR regardless of age, observed Vijay Kunadian, MBBS, MD, invited discussant for the Biscaglia presentation. “My oldest patient is 98,” she said, “and it is beneficial without a doubt.”
But Dr. Kunadian, from Newcastle (England) University, said that the trial results can’t be generalized to all older patients. That’s because their outcomes after CR could vary depending on, for example, their different frailties or comorbidities, cognition, or CV history. “So, there is an absolute need to individualize care.”
FIRE enrolled patients 75 years or older with MVD, about 64% male, who had been admitted with acute STEMI or NSTEMI at 34 sites in Italy, Spain, and Poland. All underwent successful culprit-lesion PCI using, as “strongly” recommended, the same model of sirolimus-eluting stent.
Patients were randomly assigned to physiology-guided CR of nonculprit lesions, at the same session or at least during the same hospitalization, or to no further revascularization: 720 and 725 patients, respectively.
The hazard ratio for the composite primary outcome, CR versus culprit-only PCI was 0.73 (95% confidence interval, 0.57-0.93; P = .01). The benefit was driven by reductions in three individual components of the primary endpoint: death, MI, and revascularization, but not stroke.
The HR for CV death or MI was 0.64 (95% CI, 0.47-0.88) and for death from any cause was 0.70 (95% CI, 0.51-0.96).
There was no significant difference in the primary safety outcome, a composite of contrast-related acute kidney injury, stroke, or Bleeding Academic Research Consortium grade 3 to 5 bleeding at 1 year. The rates were 22.5% in those assigned to CR and 20.4% in the culprit-only group.
The functional effect of individual lesions was assessed by either of two methods, crossing them with a standard “pressure wire” or by angiographic derivation of their quantitative flow ratio.
The choice was “left to operator discretion,” Dr. Biscaglia said in an interview, “because we wanted to mirror clinical practice at the participating centers.” Still, the CR primary benefit was independent of the physiology-guidance method.
FIRE’s sponsor – the nonprofit Consorzio Futuro in Ricerca, Italy – received grant support from Sahajanand Medical Technologies, Medis Medical Imaging systems, Eukon, Siemens Healthineers, General Electric Healthcare, and Insight Lifetech. Dr. Biscaglia had no other disclosures. Dr. Mehta reported receiving grants from Abbott Vascular and personal fees from Amgen, Janssen, and Bristol Myers Squibb. Dr. Bhatt reported numerous disclosures with various companies and organizations. Dr. Kunadian had no disclosures.
A version of this article first appeared on Medscape.com.
(MVD) in a large, randomized trial.
In the study with more than 1,400 patients, CR was guided by assessments of the functional effect of coronary lesions other than the MI culprit, a process that selects or excludes the lesions, regardless of angiographic profile, as targets for percutaneous coronary intervention (PCI).
Such physiology-guided CR led to a significant 27% drop in risk for a composite primary endpoint over 1 year in the trial, called FIRE (Functional Assessment in Elderly MI Patients with Multivessel Disease), compared with the culprit-only approach. The endpoint included death, MI, stroke, or ischemia-driven revascularization.
Risk for cardiovascular (CV) death or MI fell by 36% in the trial, and all-cause mortality declined 30%. The differences were significant, although the study wasn’t powered for those secondary endpoints. Safety outcomes were similar for the two revascularization approaches.
FIRE was noteworthy for entering only patients with ST-segment elevation or non–ST-segment elevation MI (STEMI or NSTEMI) who were age 75 years or older, a higher-risk age group poorly represented in earlier CR trials. Such patients in practice are usually managed with the culprit lesion–only approach because of a lack of good evidence supporting CR, observed Simone Biscaglia, MD, the study’s principal investigator.
“This is the first trial actually showing a benefit” from physiology-guided CR in older patients with acute MI that is similar to what the strategy can offer younger patients, said Dr. Biscaglia, from Azienda Ospedaliera Universitaria S. Anna, Ferrara, Italy.
Biscaglia made the comments at a media briefing on FIRE held during the annual congress of the European Society of Cardiology, where he presented the study. He is also lead author on its publication in the New England Journal of Medicine.
“This is a remarkable trial that adds substantially to prior studies that examined the topic of complete versus culprit-only revascularization,” Deepak L. Bhatt, MD, MPH, Icahn School of Medicine at Mount Sinai, New York, said in an interview.
It shows “quite clearly” that physiology-guided CR is superior to the culprit-only approach in patients with acute MI, said Dr. Bhatt, who is also director of Mount Sinai Heart at Mount Sinai Hospital and not connected to FIRE.
The primary findings applied to a range of different patient subgroups, including those older than 80. That’s important, he said, because “it is sometimes incorrectly assumed that patients who are older may not benefit from complete revascularization in this setting.”
And the trial’s finding of reduced risk for CV death or MI in the CR group “really should make the complete revascularization approach the standard of care in MI patients without contraindications,” Dr. Bhatt said. And certainly, “age per se should no longer be considered a contraindication.”
“First and foremost, the FIRE trial confirms the benefit of complete revascularization that has been observed in previous trials and provides additional evidence for this approach in older patients,” wrote the author of an editorial accompanying the published report.
The mortality reduction with CR at 1 years “is particularly notable” and underscores that CR should be considered in all patients with acute MI, “regardless of age,” wrote Shamir R. Mehta, MD, McMaster University, Hamilton, Ont., and Hamilton Health Sciences.
Dr. Mehta was principal investigator for the 2019 COMPLETE trial, which made the case for CR, guided by standard angiography, in patients with MVD and STEMI; their age averaged about 62 years.
FIRE definitely ought to sway practice toward greater use of physiology-guided CR regardless of age, observed Vijay Kunadian, MBBS, MD, invited discussant for the Biscaglia presentation. “My oldest patient is 98,” she said, “and it is beneficial without a doubt.”
But Dr. Kunadian, from Newcastle (England) University, said that the trial results can’t be generalized to all older patients. That’s because their outcomes after CR could vary depending on, for example, their different frailties or comorbidities, cognition, or CV history. “So, there is an absolute need to individualize care.”
FIRE enrolled patients 75 years or older with MVD, about 64% male, who had been admitted with acute STEMI or NSTEMI at 34 sites in Italy, Spain, and Poland. All underwent successful culprit-lesion PCI using, as “strongly” recommended, the same model of sirolimus-eluting stent.
Patients were randomly assigned to physiology-guided CR of nonculprit lesions, at the same session or at least during the same hospitalization, or to no further revascularization: 720 and 725 patients, respectively.
The hazard ratio for the composite primary outcome, CR versus culprit-only PCI was 0.73 (95% confidence interval, 0.57-0.93; P = .01). The benefit was driven by reductions in three individual components of the primary endpoint: death, MI, and revascularization, but not stroke.
The HR for CV death or MI was 0.64 (95% CI, 0.47-0.88) and for death from any cause was 0.70 (95% CI, 0.51-0.96).
There was no significant difference in the primary safety outcome, a composite of contrast-related acute kidney injury, stroke, or Bleeding Academic Research Consortium grade 3 to 5 bleeding at 1 year. The rates were 22.5% in those assigned to CR and 20.4% in the culprit-only group.
The functional effect of individual lesions was assessed by either of two methods, crossing them with a standard “pressure wire” or by angiographic derivation of their quantitative flow ratio.
The choice was “left to operator discretion,” Dr. Biscaglia said in an interview, “because we wanted to mirror clinical practice at the participating centers.” Still, the CR primary benefit was independent of the physiology-guidance method.
FIRE’s sponsor – the nonprofit Consorzio Futuro in Ricerca, Italy – received grant support from Sahajanand Medical Technologies, Medis Medical Imaging systems, Eukon, Siemens Healthineers, General Electric Healthcare, and Insight Lifetech. Dr. Biscaglia had no other disclosures. Dr. Mehta reported receiving grants from Abbott Vascular and personal fees from Amgen, Janssen, and Bristol Myers Squibb. Dr. Bhatt reported numerous disclosures with various companies and organizations. Dr. Kunadian had no disclosures.
A version of this article first appeared on Medscape.com.
FROM THE ESC CONGRESS 2023
ESC backs SGLT2 inhibitor plus GLP-1 in diabetes with high CVD risk
AMSTERDAM – The era of guidelines that recommended treatment with either a sodium-glucose cotransporter-2 (SGLT-2) inhibitor or a glucagonlike peptide-1 (GLP-1) receptor agonist in people with type 2 diabetes mellitus and established cardiovascular disease (CVD) ended with new recommendations from the European Society of Cardiology that call for starting both classes simultaneously.
said Darren K. McGuire, MD, at the annual congress of the European Society of Cardiology.
The society’s new guidelines for managing CVD in patients with diabetes, released on Aug. 25 and presented in several sessions at the Congress, also break with the past by calling for starting treatment with both an SGLT-2 inhibitor and a GLP-1 receptor agonist without regard to a person’s existing level of glucose control, including their current and target hemoglobin A1c levels, and regardless of background therapy, added Dr. McGuire, a cardiologist and professor at the UT Southwestern Medical Center in Dallas and a member of the ESC panel that wrote the new guidelines.
Instead, the new guidance calls for starting both drug classes promptly in people diagnosed with type 2 diabetes and established atherosclerotic CVD.
Both the previous ESC guidelines from 2019 as well as the current Standards of Care for 2023 document from the American Diabetes Association call for using one class or the other, but they hedge on combined treatment as discretionary.
Different mechanisms mean additive benefits
“With increasing numbers of patients with type 2 diabetes in trials for SGLT-2 inhibitors or GLP-1 receptor agonists who were also on the other drug class, we’ve done large, stratified analyses that suggest no treatment-effect modification” when people received agents from both drug classes, Dr. McGuire explained in an interview. “While we don’t understand the mechanisms of action of these drugs for CVD, we’ve become very confident that they use different mechanisms” that appear to have at least partially additive effects.
“Their benefits for CVD risk reduction are completely independent of their glucose effects. They are cardiology drugs,” Dr. McGuire added.
The new ESC guidelines highlight two other clinical settings where people with type 2 diabetes should receive an SGLT-2 inhibitor regardless of their existing level of glucose control and any other medical treatment: people with heart failure and people with chronic kidney disease (CKD) based on a depressed estimated glomerular filtration rate and an elevated urine albumin-to-creatinine ratio.
Nephropathy was considered by the ESC’s guideline panel to confer risk that is similar to that of established atherosclerotic CVD, Dr. McGuire said.
The guidelines also, for the first time for ESC recommendations, made treatment with finerenone (Kerendia, Bayer) a class 1 level A recommendation for people with type 2 diabetes and CKD.
SCORE2-Diabetes risk estimator
Another major change in the new ESC guideline revision is introduction of a CVD risk calculator intended to estimate the risk among people with type 2 diabetes but without established CVD, heart failure, or CKD.
Called the SCORE2-Diabetes risk estimator, it calculates a person’s 10-year risk for CVD and includes adjustment based on the European region where a person lives; it also tallies different risk levels for women and for men.
The researchers who developed the SCORE2-Diabetes calculator used data from nearly 230,000 people to devise the tool and then validated it with data from an additional 217,000 Europeans with type 2 diabetes.
Key features of the calculator include its use of routinely collected clinical values, such as age, sex, systolic blood pressure, smoking status, serum cholesterol levels, age at diabetes diagnosis, hemoglobin A1c level, and estimated glomerular filtration rate.
“For the first time we have a clear score to categorize risk” in people with type 2 diabetes and identify who needs more aggressive treatment to prevent CVD development,” said Emanuele Di Angelantonio, MD, PhD, deputy director of the cardiovascular epidemiology unit at the University of Cambridge (England).
The guidelines say that people who have a low (< 5%) or moderate (5%-9%) 10-year risk for CVD are possible candidates for metformin treatment. Those with high (10%-19%) or very high (≥ 20%) risk are possible candidates for treatment with metformin and/or an SGLT-2 inhibitor and/or a GLP-1 receptor agonist, said Dr. Di Angelantonio during his talk at the congress on the new risk score.
“The risk score is a good addition” because it estimates future CVD risk better and more systematically than usual practice, which generally relies on no systematic tool, said Naveed Sattar, PhD, professor of metabolic medicine at the University of Glasgow (Scotland) and also a member of the guideline-writing panel.
The new risk score “is a reasonable way” to identify people without CVD but at elevated risk who might benefit from treatment with a relatively expensive drug, such as an SGLT-2 inhibitor, Dr. Sattar said in an interview. “It doesn’t rely on any fancy biomarkers or imaging, and it takes about 30 seconds to calculate. It’s not perfect, but it gets the job done,” and it will increase the number of people with type 2 diabetes who will receive an SGLT-2 inhibitor, he predicted.
Dr. McGuire has been a consultant to Altimmune, Applied Therapeutics, AstraZeneca, Bayer, Boehringer-Ingelheim, Intercept, Lexion, Lilly, Merck, New Amsterdam, and Pfizer. Dr. Di Angelantonio had no disclosures. Dr. Sattar has been a consultant to Abbott, Amgen, AstraZeneca, Boehringer Ingelheim, Lilly, Novartis, Novo Nordisk, Pfizer, and Roche Diagnostics.
A version of this article appeared on Medscape.com.
AMSTERDAM – The era of guidelines that recommended treatment with either a sodium-glucose cotransporter-2 (SGLT-2) inhibitor or a glucagonlike peptide-1 (GLP-1) receptor agonist in people with type 2 diabetes mellitus and established cardiovascular disease (CVD) ended with new recommendations from the European Society of Cardiology that call for starting both classes simultaneously.
said Darren K. McGuire, MD, at the annual congress of the European Society of Cardiology.
The society’s new guidelines for managing CVD in patients with diabetes, released on Aug. 25 and presented in several sessions at the Congress, also break with the past by calling for starting treatment with both an SGLT-2 inhibitor and a GLP-1 receptor agonist without regard to a person’s existing level of glucose control, including their current and target hemoglobin A1c levels, and regardless of background therapy, added Dr. McGuire, a cardiologist and professor at the UT Southwestern Medical Center in Dallas and a member of the ESC panel that wrote the new guidelines.
Instead, the new guidance calls for starting both drug classes promptly in people diagnosed with type 2 diabetes and established atherosclerotic CVD.
Both the previous ESC guidelines from 2019 as well as the current Standards of Care for 2023 document from the American Diabetes Association call for using one class or the other, but they hedge on combined treatment as discretionary.
Different mechanisms mean additive benefits
“With increasing numbers of patients with type 2 diabetes in trials for SGLT-2 inhibitors or GLP-1 receptor agonists who were also on the other drug class, we’ve done large, stratified analyses that suggest no treatment-effect modification” when people received agents from both drug classes, Dr. McGuire explained in an interview. “While we don’t understand the mechanisms of action of these drugs for CVD, we’ve become very confident that they use different mechanisms” that appear to have at least partially additive effects.
“Their benefits for CVD risk reduction are completely independent of their glucose effects. They are cardiology drugs,” Dr. McGuire added.
The new ESC guidelines highlight two other clinical settings where people with type 2 diabetes should receive an SGLT-2 inhibitor regardless of their existing level of glucose control and any other medical treatment: people with heart failure and people with chronic kidney disease (CKD) based on a depressed estimated glomerular filtration rate and an elevated urine albumin-to-creatinine ratio.
Nephropathy was considered by the ESC’s guideline panel to confer risk that is similar to that of established atherosclerotic CVD, Dr. McGuire said.
The guidelines also, for the first time for ESC recommendations, made treatment with finerenone (Kerendia, Bayer) a class 1 level A recommendation for people with type 2 diabetes and CKD.
SCORE2-Diabetes risk estimator
Another major change in the new ESC guideline revision is introduction of a CVD risk calculator intended to estimate the risk among people with type 2 diabetes but without established CVD, heart failure, or CKD.
Called the SCORE2-Diabetes risk estimator, it calculates a person’s 10-year risk for CVD and includes adjustment based on the European region where a person lives; it also tallies different risk levels for women and for men.
The researchers who developed the SCORE2-Diabetes calculator used data from nearly 230,000 people to devise the tool and then validated it with data from an additional 217,000 Europeans with type 2 diabetes.
Key features of the calculator include its use of routinely collected clinical values, such as age, sex, systolic blood pressure, smoking status, serum cholesterol levels, age at diabetes diagnosis, hemoglobin A1c level, and estimated glomerular filtration rate.
“For the first time we have a clear score to categorize risk” in people with type 2 diabetes and identify who needs more aggressive treatment to prevent CVD development,” said Emanuele Di Angelantonio, MD, PhD, deputy director of the cardiovascular epidemiology unit at the University of Cambridge (England).
The guidelines say that people who have a low (< 5%) or moderate (5%-9%) 10-year risk for CVD are possible candidates for metformin treatment. Those with high (10%-19%) or very high (≥ 20%) risk are possible candidates for treatment with metformin and/or an SGLT-2 inhibitor and/or a GLP-1 receptor agonist, said Dr. Di Angelantonio during his talk at the congress on the new risk score.
“The risk score is a good addition” because it estimates future CVD risk better and more systematically than usual practice, which generally relies on no systematic tool, said Naveed Sattar, PhD, professor of metabolic medicine at the University of Glasgow (Scotland) and also a member of the guideline-writing panel.
The new risk score “is a reasonable way” to identify people without CVD but at elevated risk who might benefit from treatment with a relatively expensive drug, such as an SGLT-2 inhibitor, Dr. Sattar said in an interview. “It doesn’t rely on any fancy biomarkers or imaging, and it takes about 30 seconds to calculate. It’s not perfect, but it gets the job done,” and it will increase the number of people with type 2 diabetes who will receive an SGLT-2 inhibitor, he predicted.
Dr. McGuire has been a consultant to Altimmune, Applied Therapeutics, AstraZeneca, Bayer, Boehringer-Ingelheim, Intercept, Lexion, Lilly, Merck, New Amsterdam, and Pfizer. Dr. Di Angelantonio had no disclosures. Dr. Sattar has been a consultant to Abbott, Amgen, AstraZeneca, Boehringer Ingelheim, Lilly, Novartis, Novo Nordisk, Pfizer, and Roche Diagnostics.
A version of this article appeared on Medscape.com.
AMSTERDAM – The era of guidelines that recommended treatment with either a sodium-glucose cotransporter-2 (SGLT-2) inhibitor or a glucagonlike peptide-1 (GLP-1) receptor agonist in people with type 2 diabetes mellitus and established cardiovascular disease (CVD) ended with new recommendations from the European Society of Cardiology that call for starting both classes simultaneously.
said Darren K. McGuire, MD, at the annual congress of the European Society of Cardiology.
The society’s new guidelines for managing CVD in patients with diabetes, released on Aug. 25 and presented in several sessions at the Congress, also break with the past by calling for starting treatment with both an SGLT-2 inhibitor and a GLP-1 receptor agonist without regard to a person’s existing level of glucose control, including their current and target hemoglobin A1c levels, and regardless of background therapy, added Dr. McGuire, a cardiologist and professor at the UT Southwestern Medical Center in Dallas and a member of the ESC panel that wrote the new guidelines.
Instead, the new guidance calls for starting both drug classes promptly in people diagnosed with type 2 diabetes and established atherosclerotic CVD.
Both the previous ESC guidelines from 2019 as well as the current Standards of Care for 2023 document from the American Diabetes Association call for using one class or the other, but they hedge on combined treatment as discretionary.
Different mechanisms mean additive benefits
“With increasing numbers of patients with type 2 diabetes in trials for SGLT-2 inhibitors or GLP-1 receptor agonists who were also on the other drug class, we’ve done large, stratified analyses that suggest no treatment-effect modification” when people received agents from both drug classes, Dr. McGuire explained in an interview. “While we don’t understand the mechanisms of action of these drugs for CVD, we’ve become very confident that they use different mechanisms” that appear to have at least partially additive effects.
“Their benefits for CVD risk reduction are completely independent of their glucose effects. They are cardiology drugs,” Dr. McGuire added.
The new ESC guidelines highlight two other clinical settings where people with type 2 diabetes should receive an SGLT-2 inhibitor regardless of their existing level of glucose control and any other medical treatment: people with heart failure and people with chronic kidney disease (CKD) based on a depressed estimated glomerular filtration rate and an elevated urine albumin-to-creatinine ratio.
Nephropathy was considered by the ESC’s guideline panel to confer risk that is similar to that of established atherosclerotic CVD, Dr. McGuire said.
The guidelines also, for the first time for ESC recommendations, made treatment with finerenone (Kerendia, Bayer) a class 1 level A recommendation for people with type 2 diabetes and CKD.
SCORE2-Diabetes risk estimator
Another major change in the new ESC guideline revision is introduction of a CVD risk calculator intended to estimate the risk among people with type 2 diabetes but without established CVD, heart failure, or CKD.
Called the SCORE2-Diabetes risk estimator, it calculates a person’s 10-year risk for CVD and includes adjustment based on the European region where a person lives; it also tallies different risk levels for women and for men.
The researchers who developed the SCORE2-Diabetes calculator used data from nearly 230,000 people to devise the tool and then validated it with data from an additional 217,000 Europeans with type 2 diabetes.
Key features of the calculator include its use of routinely collected clinical values, such as age, sex, systolic blood pressure, smoking status, serum cholesterol levels, age at diabetes diagnosis, hemoglobin A1c level, and estimated glomerular filtration rate.
“For the first time we have a clear score to categorize risk” in people with type 2 diabetes and identify who needs more aggressive treatment to prevent CVD development,” said Emanuele Di Angelantonio, MD, PhD, deputy director of the cardiovascular epidemiology unit at the University of Cambridge (England).
The guidelines say that people who have a low (< 5%) or moderate (5%-9%) 10-year risk for CVD are possible candidates for metformin treatment. Those with high (10%-19%) or very high (≥ 20%) risk are possible candidates for treatment with metformin and/or an SGLT-2 inhibitor and/or a GLP-1 receptor agonist, said Dr. Di Angelantonio during his talk at the congress on the new risk score.
“The risk score is a good addition” because it estimates future CVD risk better and more systematically than usual practice, which generally relies on no systematic tool, said Naveed Sattar, PhD, professor of metabolic medicine at the University of Glasgow (Scotland) and also a member of the guideline-writing panel.
The new risk score “is a reasonable way” to identify people without CVD but at elevated risk who might benefit from treatment with a relatively expensive drug, such as an SGLT-2 inhibitor, Dr. Sattar said in an interview. “It doesn’t rely on any fancy biomarkers or imaging, and it takes about 30 seconds to calculate. It’s not perfect, but it gets the job done,” and it will increase the number of people with type 2 diabetes who will receive an SGLT-2 inhibitor, he predicted.
Dr. McGuire has been a consultant to Altimmune, Applied Therapeutics, AstraZeneca, Bayer, Boehringer-Ingelheim, Intercept, Lexion, Lilly, Merck, New Amsterdam, and Pfizer. Dr. Di Angelantonio had no disclosures. Dr. Sattar has been a consultant to Abbott, Amgen, AstraZeneca, Boehringer Ingelheim, Lilly, Novartis, Novo Nordisk, Pfizer, and Roche Diagnostics.
A version of this article appeared on Medscape.com.
AT ESC CONGRESS 2023
Acoramidis shows encouraging results in ATTR cardiomyopathy
AMSTERDAM –
The drug, acoramidis (BridgeBio Pharma), showed a significant reduction, compared with placebo, in the primary endpoint, a hierarchical analysis of all-cause mortality, cumulative frequency of cardiovascular hospitalizations, and change from baseline in N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) and 6-minute walking distance, in the ATTRibute-CM trial.
The combination of all-cause mortality/cardiovascular hospitalization was also significantly reduced.
The trial was presented at the annual congress of the European Society of Cardiology by Julian Gillmore, MD, head of the University College London Centre for Amyloidosis.
“ATTRibute-CM was a robustly positive trial, showing benefits across the board for acoramidis, and suggest the tantalizing possibility of genuine clinical improvements,” Dr. Gillmore concluded.
ATTR-CM is a debilitating and progressive condition that increases mortality and reduces quality of life. Although this form of cardiomyopathy was considered to be very rare not long ago, improvements in imaging techniques and treatment developments have resulted in an upsurge in diagnosis throughout the world, and the disease is being diagnosed at an earlier stage, Dr. Gillmore noted.
ATTR-CM results from aggregation and deposition of transthyretin amyloid fibrils in the heart and various tissues. Acoramidis stabilizes the TTR tetramer and avoids the production of the fibrils.
Another similar drug, tafamidis (Vyndaqel, Vyndamax, Pfizer), was approved by the Food and Drug Administration in 2019 for ATTR-CM and is now available in several counties, including Japan and Europe.
BridgeBio Pharma is planning to file for FDA approval for acoramidis toward the end of 2023 and in other countries in 2024, Dr. Gillmore reported.
“It will be a huge benefit to patients to have another effective drug available,” he said.
Tafamidis also showed impressive results with its pivotal trial – ATTR-ACT – including a significant reduction in all-cause mortality, which was not seen in the ATTRibute-CM trial with acoramidis.
Asked about this, Dr. Gillmore replied: “It is difficult to comment on comparison with tafamidis as there isn’t a head-to-head trial. All I can say is that these results with acoramidis are fantastically encouraging, and I think we are going to have two effective drugs to treat this progressive and fatal condition.”
He elaborated that the difference in all-cause mortality results between the trials was “entirely consistent” with differences in the trial populations, with the ATTRibute-CM trial recruiting much lower-risk patients, in line with the earlier diagnosis of the condition that is now occurring.
“The survival in the placebo group in the ATTRibute study was greater than that in the treatment group in the ATTR-ACT study. So, it’s not all that surprising, given the reduced number of events, that mortality alone was not statistically significant in ATTRibute. What is important is that the trend in mortality was in the right direction, with an impressive risk reduction,” Dr. Gillmore noted.
“Incredibly, survival at 30 months and hospitalization rates among patients receiving acoramidis approached that of age-matched individuals who do not have ATTR,” he added.
Noting that more patients in the placebo group started taking tafamidis during the trial, Dr. Gillmore suggested that this would be expected to dilute the treatment effect of acoramidis.
“To have such a strongly positive study despite the change in the patient population and drop-in use of tafamidis is incredibly powerful,” he concluded.
ATTRibute trial
The randomized double-blind ATTRibute-CM trial included 632 patients with ATTR-CM and New York Heart Association class I-III heart failure.
They were randomly assigned 2:1 to acoramidis (800 mg twice daily) or placebo, with a follow-up of 30 months. After the first 12 months, tafamidis was permitted if available. This was more prevalent in the placebo arm (22% vs. 14%).
The trial met the primary endpoint – a hierarchical analysis of all-cause mortality, cumulative frequency of cardiovascular hospitalizations, and change from baseline in NT-proBNP and 6-minute walking distance – with a win ratio of 1.8, which was highly statistically significant (P < .0001).
Results were consistent across all components of the primary endpoint and across all subgroups, Dr. Gillmore reported.
“Importantly, 58% of the win ratio ties were broken by the first two components of the hierarchical analysis – all-cause mortality and cardiovascular hospitalizations – and a separate analysis of these two components alone was also statistically significant,” he noted.
A trend was seen toward a treatment effect on all-cause mortality favoring acoramidis, with an 81% survival rate in the treated group, representing an absolute risk reduction of 6.4 percentage points and a relative risk reduction of 25%.
Of the deaths reported in the study, 78% were cardiovascular in nature. Cardiovascular death also showed a trend favoring treatment with the study drug (14.9% in the acoramidis group vs. 21.3% in the placebo group), giving an absolute risk reduction of 6.4 percentage points and a relative risk reduction of 30%.
Acoramidis was also associated with 50% reduction in cardiovascular hospitalizations, which was highly significant (P < .0001).
A treatment effect was also seen in terms of functional status; at 30 months, the difference in 6-minute walk distance between the groups was 40 meters, a “highly statistically significant improvement and clinically important difference, Dr. Gillmore said. Improvement from baseline occurred in 40% of the acoramidis group versus 22% of the placebo group.
Acoramidis recipients showed a blunting of the progressive rise of NT-proBNP, which Dr. Gillmore noted has been shown to be strongly associated with outcomes, with 45% of the acoramidis treated patients showing an improvement in NT-proBNP levels, compared with 9% of placebo group.
There was also a relative preservation of quality of life in the acoramidis group consistent with the separation of NT-proBNP curves, he added.
“Consistent with the mechanism of action and preclinical data showing near-complete stabilization of TTR at therapeutic drug concentrations, serum TTR (an in vivo reflection of TTR stabilization) was promptly and persistently elevated in patients receiving acoramidis,” Dr. Gillmore said.
Safety data showed that treatment-related adverse events were equal between the two groups, and there were fewer treatment emergent serious adverse events in the acoramidis group. The drug was said to be “generally well tolerated, with no findings of potential clinical concern.”
Second primary endpoint not significant
Discussant of the study at the ESC Hotline session, Thibaud Damy, MD, Hospital Henri Mondor, Paris East Creteil University, pointed out that a second primary endpoint of the study, change from baseline to month 12 in the 6-minute walking test, did not significantly differ between acoramidis and placebo.
Dr. Damy also highlighted the significant all-cause mortality reduction seen with tafamidis in ATTR-ACT but not achieved with acoramidis in ATTRibute.
He agreed with Dr. Gillmore’s interpretation that this was probably stemmed from the ATTRibute trial recruiting lower-risk patients, pointing out that patients in this trial had lower levels of NT-proBNP and less severe heart failure.
“It is clear that there is a place for acoramidis in patients with ATTR-CM,” Dr. Damy concluded, adding that many other treatments are in development.
The ATTribute trial was supported by BridgeBio Pharma. Dr. Gillmore reported advisory/consultant roles with BridgeBio, Alnylam, Ionis, AstraZeneca, Intellia, Pfizer, ATTRalus, and Lycia.
A version of this article first appeared on Medscape.com.
AMSTERDAM –
The drug, acoramidis (BridgeBio Pharma), showed a significant reduction, compared with placebo, in the primary endpoint, a hierarchical analysis of all-cause mortality, cumulative frequency of cardiovascular hospitalizations, and change from baseline in N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) and 6-minute walking distance, in the ATTRibute-CM trial.
The combination of all-cause mortality/cardiovascular hospitalization was also significantly reduced.
The trial was presented at the annual congress of the European Society of Cardiology by Julian Gillmore, MD, head of the University College London Centre for Amyloidosis.
“ATTRibute-CM was a robustly positive trial, showing benefits across the board for acoramidis, and suggest the tantalizing possibility of genuine clinical improvements,” Dr. Gillmore concluded.
ATTR-CM is a debilitating and progressive condition that increases mortality and reduces quality of life. Although this form of cardiomyopathy was considered to be very rare not long ago, improvements in imaging techniques and treatment developments have resulted in an upsurge in diagnosis throughout the world, and the disease is being diagnosed at an earlier stage, Dr. Gillmore noted.
ATTR-CM results from aggregation and deposition of transthyretin amyloid fibrils in the heart and various tissues. Acoramidis stabilizes the TTR tetramer and avoids the production of the fibrils.
Another similar drug, tafamidis (Vyndaqel, Vyndamax, Pfizer), was approved by the Food and Drug Administration in 2019 for ATTR-CM and is now available in several counties, including Japan and Europe.
BridgeBio Pharma is planning to file for FDA approval for acoramidis toward the end of 2023 and in other countries in 2024, Dr. Gillmore reported.
“It will be a huge benefit to patients to have another effective drug available,” he said.
Tafamidis also showed impressive results with its pivotal trial – ATTR-ACT – including a significant reduction in all-cause mortality, which was not seen in the ATTRibute-CM trial with acoramidis.
Asked about this, Dr. Gillmore replied: “It is difficult to comment on comparison with tafamidis as there isn’t a head-to-head trial. All I can say is that these results with acoramidis are fantastically encouraging, and I think we are going to have two effective drugs to treat this progressive and fatal condition.”
He elaborated that the difference in all-cause mortality results between the trials was “entirely consistent” with differences in the trial populations, with the ATTRibute-CM trial recruiting much lower-risk patients, in line with the earlier diagnosis of the condition that is now occurring.
“The survival in the placebo group in the ATTRibute study was greater than that in the treatment group in the ATTR-ACT study. So, it’s not all that surprising, given the reduced number of events, that mortality alone was not statistically significant in ATTRibute. What is important is that the trend in mortality was in the right direction, with an impressive risk reduction,” Dr. Gillmore noted.
“Incredibly, survival at 30 months and hospitalization rates among patients receiving acoramidis approached that of age-matched individuals who do not have ATTR,” he added.
Noting that more patients in the placebo group started taking tafamidis during the trial, Dr. Gillmore suggested that this would be expected to dilute the treatment effect of acoramidis.
“To have such a strongly positive study despite the change in the patient population and drop-in use of tafamidis is incredibly powerful,” he concluded.
ATTRibute trial
The randomized double-blind ATTRibute-CM trial included 632 patients with ATTR-CM and New York Heart Association class I-III heart failure.
They were randomly assigned 2:1 to acoramidis (800 mg twice daily) or placebo, with a follow-up of 30 months. After the first 12 months, tafamidis was permitted if available. This was more prevalent in the placebo arm (22% vs. 14%).
The trial met the primary endpoint – a hierarchical analysis of all-cause mortality, cumulative frequency of cardiovascular hospitalizations, and change from baseline in NT-proBNP and 6-minute walking distance – with a win ratio of 1.8, which was highly statistically significant (P < .0001).
Results were consistent across all components of the primary endpoint and across all subgroups, Dr. Gillmore reported.
“Importantly, 58% of the win ratio ties were broken by the first two components of the hierarchical analysis – all-cause mortality and cardiovascular hospitalizations – and a separate analysis of these two components alone was also statistically significant,” he noted.
A trend was seen toward a treatment effect on all-cause mortality favoring acoramidis, with an 81% survival rate in the treated group, representing an absolute risk reduction of 6.4 percentage points and a relative risk reduction of 25%.
Of the deaths reported in the study, 78% were cardiovascular in nature. Cardiovascular death also showed a trend favoring treatment with the study drug (14.9% in the acoramidis group vs. 21.3% in the placebo group), giving an absolute risk reduction of 6.4 percentage points and a relative risk reduction of 30%.
Acoramidis was also associated with 50% reduction in cardiovascular hospitalizations, which was highly significant (P < .0001).
A treatment effect was also seen in terms of functional status; at 30 months, the difference in 6-minute walk distance between the groups was 40 meters, a “highly statistically significant improvement and clinically important difference, Dr. Gillmore said. Improvement from baseline occurred in 40% of the acoramidis group versus 22% of the placebo group.
Acoramidis recipients showed a blunting of the progressive rise of NT-proBNP, which Dr. Gillmore noted has been shown to be strongly associated with outcomes, with 45% of the acoramidis treated patients showing an improvement in NT-proBNP levels, compared with 9% of placebo group.
There was also a relative preservation of quality of life in the acoramidis group consistent with the separation of NT-proBNP curves, he added.
“Consistent with the mechanism of action and preclinical data showing near-complete stabilization of TTR at therapeutic drug concentrations, serum TTR (an in vivo reflection of TTR stabilization) was promptly and persistently elevated in patients receiving acoramidis,” Dr. Gillmore said.
Safety data showed that treatment-related adverse events were equal between the two groups, and there were fewer treatment emergent serious adverse events in the acoramidis group. The drug was said to be “generally well tolerated, with no findings of potential clinical concern.”
Second primary endpoint not significant
Discussant of the study at the ESC Hotline session, Thibaud Damy, MD, Hospital Henri Mondor, Paris East Creteil University, pointed out that a second primary endpoint of the study, change from baseline to month 12 in the 6-minute walking test, did not significantly differ between acoramidis and placebo.
Dr. Damy also highlighted the significant all-cause mortality reduction seen with tafamidis in ATTR-ACT but not achieved with acoramidis in ATTRibute.
He agreed with Dr. Gillmore’s interpretation that this was probably stemmed from the ATTRibute trial recruiting lower-risk patients, pointing out that patients in this trial had lower levels of NT-proBNP and less severe heart failure.
“It is clear that there is a place for acoramidis in patients with ATTR-CM,” Dr. Damy concluded, adding that many other treatments are in development.
The ATTribute trial was supported by BridgeBio Pharma. Dr. Gillmore reported advisory/consultant roles with BridgeBio, Alnylam, Ionis, AstraZeneca, Intellia, Pfizer, ATTRalus, and Lycia.
A version of this article first appeared on Medscape.com.
AMSTERDAM –
The drug, acoramidis (BridgeBio Pharma), showed a significant reduction, compared with placebo, in the primary endpoint, a hierarchical analysis of all-cause mortality, cumulative frequency of cardiovascular hospitalizations, and change from baseline in N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) and 6-minute walking distance, in the ATTRibute-CM trial.
The combination of all-cause mortality/cardiovascular hospitalization was also significantly reduced.
The trial was presented at the annual congress of the European Society of Cardiology by Julian Gillmore, MD, head of the University College London Centre for Amyloidosis.
“ATTRibute-CM was a robustly positive trial, showing benefits across the board for acoramidis, and suggest the tantalizing possibility of genuine clinical improvements,” Dr. Gillmore concluded.
ATTR-CM is a debilitating and progressive condition that increases mortality and reduces quality of life. Although this form of cardiomyopathy was considered to be very rare not long ago, improvements in imaging techniques and treatment developments have resulted in an upsurge in diagnosis throughout the world, and the disease is being diagnosed at an earlier stage, Dr. Gillmore noted.
ATTR-CM results from aggregation and deposition of transthyretin amyloid fibrils in the heart and various tissues. Acoramidis stabilizes the TTR tetramer and avoids the production of the fibrils.
Another similar drug, tafamidis (Vyndaqel, Vyndamax, Pfizer), was approved by the Food and Drug Administration in 2019 for ATTR-CM and is now available in several counties, including Japan and Europe.
BridgeBio Pharma is planning to file for FDA approval for acoramidis toward the end of 2023 and in other countries in 2024, Dr. Gillmore reported.
“It will be a huge benefit to patients to have another effective drug available,” he said.
Tafamidis also showed impressive results with its pivotal trial – ATTR-ACT – including a significant reduction in all-cause mortality, which was not seen in the ATTRibute-CM trial with acoramidis.
Asked about this, Dr. Gillmore replied: “It is difficult to comment on comparison with tafamidis as there isn’t a head-to-head trial. All I can say is that these results with acoramidis are fantastically encouraging, and I think we are going to have two effective drugs to treat this progressive and fatal condition.”
He elaborated that the difference in all-cause mortality results between the trials was “entirely consistent” with differences in the trial populations, with the ATTRibute-CM trial recruiting much lower-risk patients, in line with the earlier diagnosis of the condition that is now occurring.
“The survival in the placebo group in the ATTRibute study was greater than that in the treatment group in the ATTR-ACT study. So, it’s not all that surprising, given the reduced number of events, that mortality alone was not statistically significant in ATTRibute. What is important is that the trend in mortality was in the right direction, with an impressive risk reduction,” Dr. Gillmore noted.
“Incredibly, survival at 30 months and hospitalization rates among patients receiving acoramidis approached that of age-matched individuals who do not have ATTR,” he added.
Noting that more patients in the placebo group started taking tafamidis during the trial, Dr. Gillmore suggested that this would be expected to dilute the treatment effect of acoramidis.
“To have such a strongly positive study despite the change in the patient population and drop-in use of tafamidis is incredibly powerful,” he concluded.
ATTRibute trial
The randomized double-blind ATTRibute-CM trial included 632 patients with ATTR-CM and New York Heart Association class I-III heart failure.
They were randomly assigned 2:1 to acoramidis (800 mg twice daily) or placebo, with a follow-up of 30 months. After the first 12 months, tafamidis was permitted if available. This was more prevalent in the placebo arm (22% vs. 14%).
The trial met the primary endpoint – a hierarchical analysis of all-cause mortality, cumulative frequency of cardiovascular hospitalizations, and change from baseline in NT-proBNP and 6-minute walking distance – with a win ratio of 1.8, which was highly statistically significant (P < .0001).
Results were consistent across all components of the primary endpoint and across all subgroups, Dr. Gillmore reported.
“Importantly, 58% of the win ratio ties were broken by the first two components of the hierarchical analysis – all-cause mortality and cardiovascular hospitalizations – and a separate analysis of these two components alone was also statistically significant,” he noted.
A trend was seen toward a treatment effect on all-cause mortality favoring acoramidis, with an 81% survival rate in the treated group, representing an absolute risk reduction of 6.4 percentage points and a relative risk reduction of 25%.
Of the deaths reported in the study, 78% were cardiovascular in nature. Cardiovascular death also showed a trend favoring treatment with the study drug (14.9% in the acoramidis group vs. 21.3% in the placebo group), giving an absolute risk reduction of 6.4 percentage points and a relative risk reduction of 30%.
Acoramidis was also associated with 50% reduction in cardiovascular hospitalizations, which was highly significant (P < .0001).
A treatment effect was also seen in terms of functional status; at 30 months, the difference in 6-minute walk distance between the groups was 40 meters, a “highly statistically significant improvement and clinically important difference, Dr. Gillmore said. Improvement from baseline occurred in 40% of the acoramidis group versus 22% of the placebo group.
Acoramidis recipients showed a blunting of the progressive rise of NT-proBNP, which Dr. Gillmore noted has been shown to be strongly associated with outcomes, with 45% of the acoramidis treated patients showing an improvement in NT-proBNP levels, compared with 9% of placebo group.
There was also a relative preservation of quality of life in the acoramidis group consistent with the separation of NT-proBNP curves, he added.
“Consistent with the mechanism of action and preclinical data showing near-complete stabilization of TTR at therapeutic drug concentrations, serum TTR (an in vivo reflection of TTR stabilization) was promptly and persistently elevated in patients receiving acoramidis,” Dr. Gillmore said.
Safety data showed that treatment-related adverse events were equal between the two groups, and there were fewer treatment emergent serious adverse events in the acoramidis group. The drug was said to be “generally well tolerated, with no findings of potential clinical concern.”
Second primary endpoint not significant
Discussant of the study at the ESC Hotline session, Thibaud Damy, MD, Hospital Henri Mondor, Paris East Creteil University, pointed out that a second primary endpoint of the study, change from baseline to month 12 in the 6-minute walking test, did not significantly differ between acoramidis and placebo.
Dr. Damy also highlighted the significant all-cause mortality reduction seen with tafamidis in ATTR-ACT but not achieved with acoramidis in ATTRibute.
He agreed with Dr. Gillmore’s interpretation that this was probably stemmed from the ATTRibute trial recruiting lower-risk patients, pointing out that patients in this trial had lower levels of NT-proBNP and less severe heart failure.
“It is clear that there is a place for acoramidis in patients with ATTR-CM,” Dr. Damy concluded, adding that many other treatments are in development.
The ATTribute trial was supported by BridgeBio Pharma. Dr. Gillmore reported advisory/consultant roles with BridgeBio, Alnylam, Ionis, AstraZeneca, Intellia, Pfizer, ATTRalus, and Lycia.
A version of this article first appeared on Medscape.com.
AT THE ESC CONGRESS 2023
Pulsed field ablation challenges conventional devices in AFib
in a head-to-head trial, an outcome that might favor PFA in the context of other considerations.
“The take-home message is that this is a new technology that has important safety benefits. Patients do not have to worry about the possibility – albeit rare – of esophageal fistulae and other problems. It is faster with at least the same efficacy,” reported Vivek Y. Reddy MD, director of cardiac arrhythmia services, Mount Sinai Hospital, New York.
As opposed to conventional catheter-based thermal ablation, which isolates pulmonary veins harboring AF triggers by heating or freezing the tissue, PFA uses microsecond high-voltage electrical fields to produce cellular necrosis. It is largely nonthermal, Dr. Reddy said.
New device might spare adjacent tissue
In experimental studies, PFA has demonstrated a high degree of ablative specificity, limiting effects on adjacent tissues, such as the esophagus and phrenic nerve, he explained.
Several previous clinical studies support the specificity of the PFA ablative effect, but the ADVENT trial, which Dr. Reddy presented Aug. 27 at the annual congress of the European Society of Cardiology, is the first trial in which patients have been randomly assigned to PFA or catheter-based ablation.
The study was published online in the New England Journal of Medicine simultaneously with the ESC presentation.
The primary efficacy endpoint was the absence of a composite of endpoints indicating incomplete ablation. These included an initial procedural failure, atrial tachyarrhythmias arising after a 3-month blanking period, subsequent use of antiarrhythmic drugs, cardioversion, or repeat ablation. The primary safety endpoint involved a composite of procedure-related adverse events.
The 607 patients enrolled in this trial had AF refractory to at least one antiarrhythmic drug class. They were randomly assigned in a 1:1 ratio to PFA with a catheter system (Farapulse–Boston Scientific) or to thermal ablation.
Of the thermal approaches, radiofrequency or cryoablation was permitted, but each center was required to use just one for the control arm. For the comparison to PFA, outcomes for the two thermal techniques, which were used in similar proportions of patients, were combined based on previous evidence that these approaches perform similarly.
At 1 year, 73.3% of patients in the PFA group and 71.3% of those in the control group met the primary outcome, meaning none of the events signaling ablation failure occurred. The numeric advantage of PFA confirmed noninferiority, although an evaluation of superiority for efficacy, which was triggered by the advantage of PFA, was not significant.
As predicted by previous studies, stratification of thermal ablation approaches showed that outcomes were similar, although the proportion of patients who remained free of events at 1 year was numerically higher in the cryoablation group relative to the radiofrequency group (73.6% vs. 69.2%).
An adverse safety event occurred in 2.1% of those who underwent PFA and in 1.5% of those who underwent thermal ablation. This 0.6–percentage point difference placed PFA well within the boundary of noninferiority for safety.
Of notable events, the only death in this study occurred in the PFA group, and the only stroke occurred in the control group. Phrenic nerve palsies occurred only in the control group (2 vs. 0) while pericarditis was seen only in the PFA group (2 vs. 0). One case of pulmonary edema occurred in each group.
“Catheter ablation is quite safe and effective,” said Dr. Reddy, explaining why this comparison was conducted on the basis of noninferiority.
Dr. Reddy emphasized that noninferiority for PFA was achieved by operators with little or no experience with this technology, whereas the catheter ablations were delivered by operators who typically had previously performed hundreds of interventions.
“With experience, one would expect even better rates of success. This is the floor,” Dr. Reddy said.
Procedure time faster with PFA
Despite working with a new technology, the mean procedure performance time with PFA was faster (105 vs. 123 minutes) even though mean fluoroscopy time was longer (21.1 vs 13.9 minutes). Dr. Reddy considers the difference in procedure time a meaningful demonstration of the efficiency of PFA.
“When you look at procedure performance, it is remarkable that the procedure times were statistically significantly shorter for a first-use technology in the hands of multiple operators,” Dr. Reddy said.
There was also a statistically significant advantage for PFA regarding change in the mean pulmonary vein cross-sectional area following the procedures (0.9% vs. 12%). Dr. Reddy acknowledged that small changes in pulmonary vein dimension are not clinically meaningful, but this result “gets at the question of whether we can achieve ablation without tissue proliferation that we see with conventional ablation.”
Overall, Dr. Reddy believes that the data from ADVENT provide several reasons “to get excited about PFA,” including the efficiency of this technique in the context of at least similar efficacy but a potential for fewer adverse events.
The ESC-invited discussant, Samuel Kiil Sørensen, MD, Gentofte University Hospital, Copenhagen, agreed that the ADVENT data support PFA as an alternative to thermal ablation. He suggested that the shorter procedure times are clinically meaningful given comparable safety and efficacy.
“Which property of PFA justifies noninferiority?” he asked. “Many of the complications of AF ablation are not specific to the energy modality. The devastating complications from damage to the esophagus, pulmonary veins, and phrenic nerve that the PFA technology may eliminate are rare, so they would not be expected to change the overall complication rate in a [randomized controlled trial] of realistic size.”
However, he suggested PFA might still prove to be an incremental advance for AF. He cited previous evidence that supports the specificity of its ablative activity and emphasized that ADVENT tested a first-generation device that might not capture the full advantages of the PFA technology.
The trial was supported by Farapulse–Boston Scientific. Dr. Reddy reports financial relationships with more than 30 pharmaceutical or device manufacturers, including Farapulse–Boston Scientific. Dr. Sørensen reports financial relationships with Medtronic and Biosense Webster.
A version of this article first appeared on Medscape.com.
in a head-to-head trial, an outcome that might favor PFA in the context of other considerations.
“The take-home message is that this is a new technology that has important safety benefits. Patients do not have to worry about the possibility – albeit rare – of esophageal fistulae and other problems. It is faster with at least the same efficacy,” reported Vivek Y. Reddy MD, director of cardiac arrhythmia services, Mount Sinai Hospital, New York.
As opposed to conventional catheter-based thermal ablation, which isolates pulmonary veins harboring AF triggers by heating or freezing the tissue, PFA uses microsecond high-voltage electrical fields to produce cellular necrosis. It is largely nonthermal, Dr. Reddy said.
New device might spare adjacent tissue
In experimental studies, PFA has demonstrated a high degree of ablative specificity, limiting effects on adjacent tissues, such as the esophagus and phrenic nerve, he explained.
Several previous clinical studies support the specificity of the PFA ablative effect, but the ADVENT trial, which Dr. Reddy presented Aug. 27 at the annual congress of the European Society of Cardiology, is the first trial in which patients have been randomly assigned to PFA or catheter-based ablation.
The study was published online in the New England Journal of Medicine simultaneously with the ESC presentation.
The primary efficacy endpoint was the absence of a composite of endpoints indicating incomplete ablation. These included an initial procedural failure, atrial tachyarrhythmias arising after a 3-month blanking period, subsequent use of antiarrhythmic drugs, cardioversion, or repeat ablation. The primary safety endpoint involved a composite of procedure-related adverse events.
The 607 patients enrolled in this trial had AF refractory to at least one antiarrhythmic drug class. They were randomly assigned in a 1:1 ratio to PFA with a catheter system (Farapulse–Boston Scientific) or to thermal ablation.
Of the thermal approaches, radiofrequency or cryoablation was permitted, but each center was required to use just one for the control arm. For the comparison to PFA, outcomes for the two thermal techniques, which were used in similar proportions of patients, were combined based on previous evidence that these approaches perform similarly.
At 1 year, 73.3% of patients in the PFA group and 71.3% of those in the control group met the primary outcome, meaning none of the events signaling ablation failure occurred. The numeric advantage of PFA confirmed noninferiority, although an evaluation of superiority for efficacy, which was triggered by the advantage of PFA, was not significant.
As predicted by previous studies, stratification of thermal ablation approaches showed that outcomes were similar, although the proportion of patients who remained free of events at 1 year was numerically higher in the cryoablation group relative to the radiofrequency group (73.6% vs. 69.2%).
An adverse safety event occurred in 2.1% of those who underwent PFA and in 1.5% of those who underwent thermal ablation. This 0.6–percentage point difference placed PFA well within the boundary of noninferiority for safety.
Of notable events, the only death in this study occurred in the PFA group, and the only stroke occurred in the control group. Phrenic nerve palsies occurred only in the control group (2 vs. 0) while pericarditis was seen only in the PFA group (2 vs. 0). One case of pulmonary edema occurred in each group.
“Catheter ablation is quite safe and effective,” said Dr. Reddy, explaining why this comparison was conducted on the basis of noninferiority.
Dr. Reddy emphasized that noninferiority for PFA was achieved by operators with little or no experience with this technology, whereas the catheter ablations were delivered by operators who typically had previously performed hundreds of interventions.
“With experience, one would expect even better rates of success. This is the floor,” Dr. Reddy said.
Procedure time faster with PFA
Despite working with a new technology, the mean procedure performance time with PFA was faster (105 vs. 123 minutes) even though mean fluoroscopy time was longer (21.1 vs 13.9 minutes). Dr. Reddy considers the difference in procedure time a meaningful demonstration of the efficiency of PFA.
“When you look at procedure performance, it is remarkable that the procedure times were statistically significantly shorter for a first-use technology in the hands of multiple operators,” Dr. Reddy said.
There was also a statistically significant advantage for PFA regarding change in the mean pulmonary vein cross-sectional area following the procedures (0.9% vs. 12%). Dr. Reddy acknowledged that small changes in pulmonary vein dimension are not clinically meaningful, but this result “gets at the question of whether we can achieve ablation without tissue proliferation that we see with conventional ablation.”
Overall, Dr. Reddy believes that the data from ADVENT provide several reasons “to get excited about PFA,” including the efficiency of this technique in the context of at least similar efficacy but a potential for fewer adverse events.
The ESC-invited discussant, Samuel Kiil Sørensen, MD, Gentofte University Hospital, Copenhagen, agreed that the ADVENT data support PFA as an alternative to thermal ablation. He suggested that the shorter procedure times are clinically meaningful given comparable safety and efficacy.
“Which property of PFA justifies noninferiority?” he asked. “Many of the complications of AF ablation are not specific to the energy modality. The devastating complications from damage to the esophagus, pulmonary veins, and phrenic nerve that the PFA technology may eliminate are rare, so they would not be expected to change the overall complication rate in a [randomized controlled trial] of realistic size.”
However, he suggested PFA might still prove to be an incremental advance for AF. He cited previous evidence that supports the specificity of its ablative activity and emphasized that ADVENT tested a first-generation device that might not capture the full advantages of the PFA technology.
The trial was supported by Farapulse–Boston Scientific. Dr. Reddy reports financial relationships with more than 30 pharmaceutical or device manufacturers, including Farapulse–Boston Scientific. Dr. Sørensen reports financial relationships with Medtronic and Biosense Webster.
A version of this article first appeared on Medscape.com.
in a head-to-head trial, an outcome that might favor PFA in the context of other considerations.
“The take-home message is that this is a new technology that has important safety benefits. Patients do not have to worry about the possibility – albeit rare – of esophageal fistulae and other problems. It is faster with at least the same efficacy,” reported Vivek Y. Reddy MD, director of cardiac arrhythmia services, Mount Sinai Hospital, New York.
As opposed to conventional catheter-based thermal ablation, which isolates pulmonary veins harboring AF triggers by heating or freezing the tissue, PFA uses microsecond high-voltage electrical fields to produce cellular necrosis. It is largely nonthermal, Dr. Reddy said.
New device might spare adjacent tissue
In experimental studies, PFA has demonstrated a high degree of ablative specificity, limiting effects on adjacent tissues, such as the esophagus and phrenic nerve, he explained.
Several previous clinical studies support the specificity of the PFA ablative effect, but the ADVENT trial, which Dr. Reddy presented Aug. 27 at the annual congress of the European Society of Cardiology, is the first trial in which patients have been randomly assigned to PFA or catheter-based ablation.
The study was published online in the New England Journal of Medicine simultaneously with the ESC presentation.
The primary efficacy endpoint was the absence of a composite of endpoints indicating incomplete ablation. These included an initial procedural failure, atrial tachyarrhythmias arising after a 3-month blanking period, subsequent use of antiarrhythmic drugs, cardioversion, or repeat ablation. The primary safety endpoint involved a composite of procedure-related adverse events.
The 607 patients enrolled in this trial had AF refractory to at least one antiarrhythmic drug class. They were randomly assigned in a 1:1 ratio to PFA with a catheter system (Farapulse–Boston Scientific) or to thermal ablation.
Of the thermal approaches, radiofrequency or cryoablation was permitted, but each center was required to use just one for the control arm. For the comparison to PFA, outcomes for the two thermal techniques, which were used in similar proportions of patients, were combined based on previous evidence that these approaches perform similarly.
At 1 year, 73.3% of patients in the PFA group and 71.3% of those in the control group met the primary outcome, meaning none of the events signaling ablation failure occurred. The numeric advantage of PFA confirmed noninferiority, although an evaluation of superiority for efficacy, which was triggered by the advantage of PFA, was not significant.
As predicted by previous studies, stratification of thermal ablation approaches showed that outcomes were similar, although the proportion of patients who remained free of events at 1 year was numerically higher in the cryoablation group relative to the radiofrequency group (73.6% vs. 69.2%).
An adverse safety event occurred in 2.1% of those who underwent PFA and in 1.5% of those who underwent thermal ablation. This 0.6–percentage point difference placed PFA well within the boundary of noninferiority for safety.
Of notable events, the only death in this study occurred in the PFA group, and the only stroke occurred in the control group. Phrenic nerve palsies occurred only in the control group (2 vs. 0) while pericarditis was seen only in the PFA group (2 vs. 0). One case of pulmonary edema occurred in each group.
“Catheter ablation is quite safe and effective,” said Dr. Reddy, explaining why this comparison was conducted on the basis of noninferiority.
Dr. Reddy emphasized that noninferiority for PFA was achieved by operators with little or no experience with this technology, whereas the catheter ablations were delivered by operators who typically had previously performed hundreds of interventions.
“With experience, one would expect even better rates of success. This is the floor,” Dr. Reddy said.
Procedure time faster with PFA
Despite working with a new technology, the mean procedure performance time with PFA was faster (105 vs. 123 minutes) even though mean fluoroscopy time was longer (21.1 vs 13.9 minutes). Dr. Reddy considers the difference in procedure time a meaningful demonstration of the efficiency of PFA.
“When you look at procedure performance, it is remarkable that the procedure times were statistically significantly shorter for a first-use technology in the hands of multiple operators,” Dr. Reddy said.
There was also a statistically significant advantage for PFA regarding change in the mean pulmonary vein cross-sectional area following the procedures (0.9% vs. 12%). Dr. Reddy acknowledged that small changes in pulmonary vein dimension are not clinically meaningful, but this result “gets at the question of whether we can achieve ablation without tissue proliferation that we see with conventional ablation.”
Overall, Dr. Reddy believes that the data from ADVENT provide several reasons “to get excited about PFA,” including the efficiency of this technique in the context of at least similar efficacy but a potential for fewer adverse events.
The ESC-invited discussant, Samuel Kiil Sørensen, MD, Gentofte University Hospital, Copenhagen, agreed that the ADVENT data support PFA as an alternative to thermal ablation. He suggested that the shorter procedure times are clinically meaningful given comparable safety and efficacy.
“Which property of PFA justifies noninferiority?” he asked. “Many of the complications of AF ablation are not specific to the energy modality. The devastating complications from damage to the esophagus, pulmonary veins, and phrenic nerve that the PFA technology may eliminate are rare, so they would not be expected to change the overall complication rate in a [randomized controlled trial] of realistic size.”
However, he suggested PFA might still prove to be an incremental advance for AF. He cited previous evidence that supports the specificity of its ablative activity and emphasized that ADVENT tested a first-generation device that might not capture the full advantages of the PFA technology.
The trial was supported by Farapulse–Boston Scientific. Dr. Reddy reports financial relationships with more than 30 pharmaceutical or device manufacturers, including Farapulse–Boston Scientific. Dr. Sørensen reports financial relationships with Medtronic and Biosense Webster.
A version of this article first appeared on Medscape.com.
FROM THE ESC CONGRESS 2023
ECMO for shock in acute MI won’t help, may harm: ECLS-SHOCK
Patients with acute myocardial infarction (MI) and shock are often put on extracorporeal membrane oxygenation (ECMO) support before heading to the catheterization laboratory. But the practice, done routinely, doesn’t have much backing from randomized trials. Now it’s being challenged by one of the largest such studies to explore the issue.
ECMO-managed patients, moreover, had sharply increased risks for moderate and severe bleeding and vascular complications.
A challenge to common practice
The results undercut guidelines that promote mechanical circulatory support in MI-related cardiogenic shock primarily based on observational data, and they argue against what’s become common practice, said Holger Thiele, MD, Heart Center Leipzig, University of Leipzig, Germany.
Such use of ECMO could well offer some type of advantage in MI-related shock, but the data so far don’t show it, Dr. Thiele said at a press conference on the new study, called ECLS-SHOCK, at the annual congress of the European Society of Cardiology in Amsterdam. He formally presented the trial at the meeting and is lead author on its simultaneous publication in The New England Journal of Medicine.
Almost half of the trial’s patients died, whether or not they had been put on ECMO. All-cause mortality at 30 days, the primary endpoint, was about the same, at 47.8% and 49.0% for the ECMO and usual-care groups, respectively.
Meanwhile, Dr. Thiele reported, risks for moderate or severe bleeding more than doubled and serious peripheral vascular complications almost tripled with addition of ECMO support.
The findings, he noted, are consistent with a new meta-analysis of trials testing ECMO in MI-related shock that also showed increases in bleeding with survival gains using the devices. Dr. Thiele is senior author on that report, published in The Lancet to coincide with his ECLS-SHOCK presentation.
Would any subgroups benefit?
Importantly, he said in an interview, ECMO’s failure to improve 30-day survival in the trial probably applies across the spectrum of patients with MI-related shock. Subgroup analyses in both ECLS-SHOCK and the meta-analysis didn’t identify any groups that benefit, Dr. Thiele observed.
For example, there were no significant differences for the primary outcome by age, sex, whether the MI was ST-segment elevation MI or non–ST-segment elevation MI or anterior or nonanterior, or whether the patient had diabetes.
If there is a subgroup in MI-related shock that is likely to benefit from the intervention with lower mortality, he said, “it’s less than 1%, if you ask me.”
An accompanying editorial essentially agreed, arguing that ECLS-SHOCK contests the intervention’s broad application in MI-related shock without shedding light on any selective benefits.
“Will the results of the ECLS-SHOCK trial change current clinical practice? If the goal of [ECMO] is to improve 30-day mortality, these data should steer interventional and critical care cardiologists away from its early routine implementation for all or even most patients with myocardial infarction and cardiogenic shock,” the editorialists say.
“There will be some patients in this population for whom [ECMO] is necessary and lifesaving, but the results of the ECLS-SHOCK trial do not tell us which ones,” write Jane A. Leopold, MD, Brigham and Women’s Hospital, Boston, and Darren B. Taichman, MD, PhD, Penn Presbyterian Medical Center, Philadelphia.
“For now, the best course may be to reserve the early initiation of [ECMO] for those patients with infarct-related cardiogenic shock in whom the likely benefits more clearly outweigh the potential harms. We need further studies to tell us who they are,” write Dr. Leopold and Dr. Taichman, who are deputy editors with The New England Journal of Medicine.
ECLS-SHOCK randomly assigned 420 patients with acute MI complicated by shock and slated for coronary revascularization to receive standard care with or without early ECMO at 44 centers in Germany and Slovenia. Their median age was 63 years, and about 81% were men.
The relative risk for death from any cause, ECMO vs. usual care, was flatly nonsignificant at 0.98 (95% confidence interval, 0.80-1.19; P = .81).
ECMO came at the cost of significantly more cases of the primary safety endpoint, moderate or severe bleeding by Bleeding Academic Research Consortium criteria. That endpoint was met by 23.4% of ECMO patients and 9.6% of the control group, for an RR of 2.44 (95% CI, 1.50-3.95).
Rates of stroke or systemic embolization were nonsignificantly different at 3.8% and 2.9%, respectively (RR, 1.33; 95% CI, 0.47-3.76).
Speaking with this news organization, Sripal Bangalore, MD, MHA, pointed out that only 5.8% of the ECMO group but about 32% of those managed with usual care received some form of left ventricular (LV) unloading therapy.
Such measures can include atrial septostomy or the addition of an intra-aortic balloon pump or percutaneous LV-assist pump.
Given that ECMO increases afterload, “which is physiologically detrimental in patients with an ongoing MI, one is left to wonder if the results would have been different with greater use of LV unloading,” said Dr. Bangalore, of NYU Langone Health, New York, who isn’t associated with ECLS-SHOCK.
Also, he pointed out, about 78% of the trial’s patients had experienced some degree of cardiopulmonary resuscitation despite exclusion of anyone who had undergone it for more than 45 minutes. That may make the study more generalizable but also harder to show a benefit from ECMO. “The overall prognosis of that subset of patients despite heroic efforts is bleak at best.”
Dr. Thiele had no disclosures; statements for the other authors can be found at nejm.org. Dr. Bangalore has previously disclosed financial relationships with Abbott Vascular, Amgen, Biotronik, Inari, Pfizer, Reata, and Truvic. Dr. Leopold reports grants from Astellas and personal fees from United Therapeutics, Abbott Vascular, and North America Thrombosis Forum. Dr. Leopold and Dr. Taichman both report employment by The New England Journal of Medicine.
A version of this article appeared on Medscape.com.
Patients with acute myocardial infarction (MI) and shock are often put on extracorporeal membrane oxygenation (ECMO) support before heading to the catheterization laboratory. But the practice, done routinely, doesn’t have much backing from randomized trials. Now it’s being challenged by one of the largest such studies to explore the issue.
ECMO-managed patients, moreover, had sharply increased risks for moderate and severe bleeding and vascular complications.
A challenge to common practice
The results undercut guidelines that promote mechanical circulatory support in MI-related cardiogenic shock primarily based on observational data, and they argue against what’s become common practice, said Holger Thiele, MD, Heart Center Leipzig, University of Leipzig, Germany.
Such use of ECMO could well offer some type of advantage in MI-related shock, but the data so far don’t show it, Dr. Thiele said at a press conference on the new study, called ECLS-SHOCK, at the annual congress of the European Society of Cardiology in Amsterdam. He formally presented the trial at the meeting and is lead author on its simultaneous publication in The New England Journal of Medicine.
Almost half of the trial’s patients died, whether or not they had been put on ECMO. All-cause mortality at 30 days, the primary endpoint, was about the same, at 47.8% and 49.0% for the ECMO and usual-care groups, respectively.
Meanwhile, Dr. Thiele reported, risks for moderate or severe bleeding more than doubled and serious peripheral vascular complications almost tripled with addition of ECMO support.
The findings, he noted, are consistent with a new meta-analysis of trials testing ECMO in MI-related shock that also showed increases in bleeding with survival gains using the devices. Dr. Thiele is senior author on that report, published in The Lancet to coincide with his ECLS-SHOCK presentation.
Would any subgroups benefit?
Importantly, he said in an interview, ECMO’s failure to improve 30-day survival in the trial probably applies across the spectrum of patients with MI-related shock. Subgroup analyses in both ECLS-SHOCK and the meta-analysis didn’t identify any groups that benefit, Dr. Thiele observed.
For example, there were no significant differences for the primary outcome by age, sex, whether the MI was ST-segment elevation MI or non–ST-segment elevation MI or anterior or nonanterior, or whether the patient had diabetes.
If there is a subgroup in MI-related shock that is likely to benefit from the intervention with lower mortality, he said, “it’s less than 1%, if you ask me.”
An accompanying editorial essentially agreed, arguing that ECLS-SHOCK contests the intervention’s broad application in MI-related shock without shedding light on any selective benefits.
“Will the results of the ECLS-SHOCK trial change current clinical practice? If the goal of [ECMO] is to improve 30-day mortality, these data should steer interventional and critical care cardiologists away from its early routine implementation for all or even most patients with myocardial infarction and cardiogenic shock,” the editorialists say.
“There will be some patients in this population for whom [ECMO] is necessary and lifesaving, but the results of the ECLS-SHOCK trial do not tell us which ones,” write Jane A. Leopold, MD, Brigham and Women’s Hospital, Boston, and Darren B. Taichman, MD, PhD, Penn Presbyterian Medical Center, Philadelphia.
“For now, the best course may be to reserve the early initiation of [ECMO] for those patients with infarct-related cardiogenic shock in whom the likely benefits more clearly outweigh the potential harms. We need further studies to tell us who they are,” write Dr. Leopold and Dr. Taichman, who are deputy editors with The New England Journal of Medicine.
ECLS-SHOCK randomly assigned 420 patients with acute MI complicated by shock and slated for coronary revascularization to receive standard care with or without early ECMO at 44 centers in Germany and Slovenia. Their median age was 63 years, and about 81% were men.
The relative risk for death from any cause, ECMO vs. usual care, was flatly nonsignificant at 0.98 (95% confidence interval, 0.80-1.19; P = .81).
ECMO came at the cost of significantly more cases of the primary safety endpoint, moderate or severe bleeding by Bleeding Academic Research Consortium criteria. That endpoint was met by 23.4% of ECMO patients and 9.6% of the control group, for an RR of 2.44 (95% CI, 1.50-3.95).
Rates of stroke or systemic embolization were nonsignificantly different at 3.8% and 2.9%, respectively (RR, 1.33; 95% CI, 0.47-3.76).
Speaking with this news organization, Sripal Bangalore, MD, MHA, pointed out that only 5.8% of the ECMO group but about 32% of those managed with usual care received some form of left ventricular (LV) unloading therapy.
Such measures can include atrial septostomy or the addition of an intra-aortic balloon pump or percutaneous LV-assist pump.
Given that ECMO increases afterload, “which is physiologically detrimental in patients with an ongoing MI, one is left to wonder if the results would have been different with greater use of LV unloading,” said Dr. Bangalore, of NYU Langone Health, New York, who isn’t associated with ECLS-SHOCK.
Also, he pointed out, about 78% of the trial’s patients had experienced some degree of cardiopulmonary resuscitation despite exclusion of anyone who had undergone it for more than 45 minutes. That may make the study more generalizable but also harder to show a benefit from ECMO. “The overall prognosis of that subset of patients despite heroic efforts is bleak at best.”
Dr. Thiele had no disclosures; statements for the other authors can be found at nejm.org. Dr. Bangalore has previously disclosed financial relationships with Abbott Vascular, Amgen, Biotronik, Inari, Pfizer, Reata, and Truvic. Dr. Leopold reports grants from Astellas and personal fees from United Therapeutics, Abbott Vascular, and North America Thrombosis Forum. Dr. Leopold and Dr. Taichman both report employment by The New England Journal of Medicine.
A version of this article appeared on Medscape.com.
Patients with acute myocardial infarction (MI) and shock are often put on extracorporeal membrane oxygenation (ECMO) support before heading to the catheterization laboratory. But the practice, done routinely, doesn’t have much backing from randomized trials. Now it’s being challenged by one of the largest such studies to explore the issue.
ECMO-managed patients, moreover, had sharply increased risks for moderate and severe bleeding and vascular complications.
A challenge to common practice
The results undercut guidelines that promote mechanical circulatory support in MI-related cardiogenic shock primarily based on observational data, and they argue against what’s become common practice, said Holger Thiele, MD, Heart Center Leipzig, University of Leipzig, Germany.
Such use of ECMO could well offer some type of advantage in MI-related shock, but the data so far don’t show it, Dr. Thiele said at a press conference on the new study, called ECLS-SHOCK, at the annual congress of the European Society of Cardiology in Amsterdam. He formally presented the trial at the meeting and is lead author on its simultaneous publication in The New England Journal of Medicine.
Almost half of the trial’s patients died, whether or not they had been put on ECMO. All-cause mortality at 30 days, the primary endpoint, was about the same, at 47.8% and 49.0% for the ECMO and usual-care groups, respectively.
Meanwhile, Dr. Thiele reported, risks for moderate or severe bleeding more than doubled and serious peripheral vascular complications almost tripled with addition of ECMO support.
The findings, he noted, are consistent with a new meta-analysis of trials testing ECMO in MI-related shock that also showed increases in bleeding with survival gains using the devices. Dr. Thiele is senior author on that report, published in The Lancet to coincide with his ECLS-SHOCK presentation.
Would any subgroups benefit?
Importantly, he said in an interview, ECMO’s failure to improve 30-day survival in the trial probably applies across the spectrum of patients with MI-related shock. Subgroup analyses in both ECLS-SHOCK and the meta-analysis didn’t identify any groups that benefit, Dr. Thiele observed.
For example, there were no significant differences for the primary outcome by age, sex, whether the MI was ST-segment elevation MI or non–ST-segment elevation MI or anterior or nonanterior, or whether the patient had diabetes.
If there is a subgroup in MI-related shock that is likely to benefit from the intervention with lower mortality, he said, “it’s less than 1%, if you ask me.”
An accompanying editorial essentially agreed, arguing that ECLS-SHOCK contests the intervention’s broad application in MI-related shock without shedding light on any selective benefits.
“Will the results of the ECLS-SHOCK trial change current clinical practice? If the goal of [ECMO] is to improve 30-day mortality, these data should steer interventional and critical care cardiologists away from its early routine implementation for all or even most patients with myocardial infarction and cardiogenic shock,” the editorialists say.
“There will be some patients in this population for whom [ECMO] is necessary and lifesaving, but the results of the ECLS-SHOCK trial do not tell us which ones,” write Jane A. Leopold, MD, Brigham and Women’s Hospital, Boston, and Darren B. Taichman, MD, PhD, Penn Presbyterian Medical Center, Philadelphia.
“For now, the best course may be to reserve the early initiation of [ECMO] for those patients with infarct-related cardiogenic shock in whom the likely benefits more clearly outweigh the potential harms. We need further studies to tell us who they are,” write Dr. Leopold and Dr. Taichman, who are deputy editors with The New England Journal of Medicine.
ECLS-SHOCK randomly assigned 420 patients with acute MI complicated by shock and slated for coronary revascularization to receive standard care with or without early ECMO at 44 centers in Germany and Slovenia. Their median age was 63 years, and about 81% were men.
The relative risk for death from any cause, ECMO vs. usual care, was flatly nonsignificant at 0.98 (95% confidence interval, 0.80-1.19; P = .81).
ECMO came at the cost of significantly more cases of the primary safety endpoint, moderate or severe bleeding by Bleeding Academic Research Consortium criteria. That endpoint was met by 23.4% of ECMO patients and 9.6% of the control group, for an RR of 2.44 (95% CI, 1.50-3.95).
Rates of stroke or systemic embolization were nonsignificantly different at 3.8% and 2.9%, respectively (RR, 1.33; 95% CI, 0.47-3.76).
Speaking with this news organization, Sripal Bangalore, MD, MHA, pointed out that only 5.8% of the ECMO group but about 32% of those managed with usual care received some form of left ventricular (LV) unloading therapy.
Such measures can include atrial septostomy or the addition of an intra-aortic balloon pump or percutaneous LV-assist pump.
Given that ECMO increases afterload, “which is physiologically detrimental in patients with an ongoing MI, one is left to wonder if the results would have been different with greater use of LV unloading,” said Dr. Bangalore, of NYU Langone Health, New York, who isn’t associated with ECLS-SHOCK.
Also, he pointed out, about 78% of the trial’s patients had experienced some degree of cardiopulmonary resuscitation despite exclusion of anyone who had undergone it for more than 45 minutes. That may make the study more generalizable but also harder to show a benefit from ECMO. “The overall prognosis of that subset of patients despite heroic efforts is bleak at best.”
Dr. Thiele had no disclosures; statements for the other authors can be found at nejm.org. Dr. Bangalore has previously disclosed financial relationships with Abbott Vascular, Amgen, Biotronik, Inari, Pfizer, Reata, and Truvic. Dr. Leopold reports grants from Astellas and personal fees from United Therapeutics, Abbott Vascular, and North America Thrombosis Forum. Dr. Leopold and Dr. Taichman both report employment by The New England Journal of Medicine.
A version of this article appeared on Medscape.com.
FROM ESC CONGRESS 2023
Number of people with long COVID could be vastly underestimated
It’s been estimated that up to one-third of people who survive acute SARS-CoV-2 infection will suffer a post-viral syndrome with lingering neurologic and other symptoms – now known as long COVID or neurological postacute sequelae of SARS-CoV-2 infection (Neuro-PASC).
However, Researchers found a significant proportion of patients in their small study who had never tested positive for COVID-19 but who were having symptoms of long COVID nevertheless showed evidence of immune responses consistent with previous exposure.
“We estimate that millions of people got COVID in the U.S. during the first year of the pandemic and then developed long COVID, yet they did not get a positive COVID diagnosis because of testing limitations,” Igor J. Koralnik, MD, of Northwestern Medicine Comprehensive COVID-19 Center in Chicago, said in an interview.
He noted that many post-COVID-19 clinics in the United States don’t accept people with long COVID symptoms who do not have a positive test result.
Patients with long COVID symptoms but without laboratory evidence of prior infection, “who have often been rejected and stigmatized, should feel vindicated by the results of our study,” Dr. Koralnik said.
“We think that those patients deserve the same clinical care as those with a positive test, as well as inclusion in research studies. This is what we are doing at Northwestern Medicine’s Comprehensive COVID[-19] Center,” Dr. Koralnik added.
The study was published online in the journal Neurology: Neuroimmunology & Neuroinflammation.
Delayed care
The researchers measured SARS-CoV-2-specific humoral and cell-mediated immune responses against nucleocapsid protein and spike proteins, which indicate a prior COVID-19 infection, in 29 patients with post-viral syndrome after suspected COVID-19, including neurologic symptoms such as cognitive impairment, headache, and fatigue, but who did not have a confirmed positive COVID-19 test.
They did the same in 32 age- and sex-matched COVID long haulers with confirmed Neuro-PASC and 18 healthy controls with none of the symptoms of long COVID and no known exposure to SARS-CoV-2 or positive test result.
They found that 12 of the 29 patients (41%) with post-viral syndrome (but no positive COVID-19 test) had detectable humoral and cellular immune responses consistent with prior exposure to SARS-CoV-2. Three-quarters harbored antinucleocapsid and 50% harbored antispike responses.
“Our data suggest that at least 4 million people with post-viral syndrome similar to long COVID may indeed have detectable immune responses to support a COVID diagnosis,” Dr. Koralnik said in a news release.
The 12 patients with post-viral syndrome but without a confirmed COVID-19 test had neurologic symptoms similar to those of patients with confirmed Neuro-PASC.
However, lack of a confirmed COVID-19 diagnosis likely contributed to the 5-month delay in the median time from symptom onset to clinic visit, the researchers said. They were evaluated at a median of 10.7 months vs. 5.4 months for Neuro-PASC patients.
Dr. Koralnik said in an interview that the “most important take-home message” of the study is that patients with post-viral syndrome often present with clinical manifestations similar to those of confirmed patients with Neuro-PASC, suggesting that a positive result by commercially available SARS-CoV-2 diagnostic test should not be a prerequisite for accessing care.
Patients with post-viral syndrome may benefit from the same clinical care as confirmed patients with Neuro-PASC, and the absence of a positive SARS-CoV-2 test should not preclude or delay treatment, he added.
A version of this article first appeared on Medscape.com .
This article was updated 8/28/23.
It’s been estimated that up to one-third of people who survive acute SARS-CoV-2 infection will suffer a post-viral syndrome with lingering neurologic and other symptoms – now known as long COVID or neurological postacute sequelae of SARS-CoV-2 infection (Neuro-PASC).
However, Researchers found a significant proportion of patients in their small study who had never tested positive for COVID-19 but who were having symptoms of long COVID nevertheless showed evidence of immune responses consistent with previous exposure.
“We estimate that millions of people got COVID in the U.S. during the first year of the pandemic and then developed long COVID, yet they did not get a positive COVID diagnosis because of testing limitations,” Igor J. Koralnik, MD, of Northwestern Medicine Comprehensive COVID-19 Center in Chicago, said in an interview.
He noted that many post-COVID-19 clinics in the United States don’t accept people with long COVID symptoms who do not have a positive test result.
Patients with long COVID symptoms but without laboratory evidence of prior infection, “who have often been rejected and stigmatized, should feel vindicated by the results of our study,” Dr. Koralnik said.
“We think that those patients deserve the same clinical care as those with a positive test, as well as inclusion in research studies. This is what we are doing at Northwestern Medicine’s Comprehensive COVID[-19] Center,” Dr. Koralnik added.
The study was published online in the journal Neurology: Neuroimmunology & Neuroinflammation.
Delayed care
The researchers measured SARS-CoV-2-specific humoral and cell-mediated immune responses against nucleocapsid protein and spike proteins, which indicate a prior COVID-19 infection, in 29 patients with post-viral syndrome after suspected COVID-19, including neurologic symptoms such as cognitive impairment, headache, and fatigue, but who did not have a confirmed positive COVID-19 test.
They did the same in 32 age- and sex-matched COVID long haulers with confirmed Neuro-PASC and 18 healthy controls with none of the symptoms of long COVID and no known exposure to SARS-CoV-2 or positive test result.
They found that 12 of the 29 patients (41%) with post-viral syndrome (but no positive COVID-19 test) had detectable humoral and cellular immune responses consistent with prior exposure to SARS-CoV-2. Three-quarters harbored antinucleocapsid and 50% harbored antispike responses.
“Our data suggest that at least 4 million people with post-viral syndrome similar to long COVID may indeed have detectable immune responses to support a COVID diagnosis,” Dr. Koralnik said in a news release.
The 12 patients with post-viral syndrome but without a confirmed COVID-19 test had neurologic symptoms similar to those of patients with confirmed Neuro-PASC.
However, lack of a confirmed COVID-19 diagnosis likely contributed to the 5-month delay in the median time from symptom onset to clinic visit, the researchers said. They were evaluated at a median of 10.7 months vs. 5.4 months for Neuro-PASC patients.
Dr. Koralnik said in an interview that the “most important take-home message” of the study is that patients with post-viral syndrome often present with clinical manifestations similar to those of confirmed patients with Neuro-PASC, suggesting that a positive result by commercially available SARS-CoV-2 diagnostic test should not be a prerequisite for accessing care.
Patients with post-viral syndrome may benefit from the same clinical care as confirmed patients with Neuro-PASC, and the absence of a positive SARS-CoV-2 test should not preclude or delay treatment, he added.
A version of this article first appeared on Medscape.com .
This article was updated 8/28/23.
It’s been estimated that up to one-third of people who survive acute SARS-CoV-2 infection will suffer a post-viral syndrome with lingering neurologic and other symptoms – now known as long COVID or neurological postacute sequelae of SARS-CoV-2 infection (Neuro-PASC).
However, Researchers found a significant proportion of patients in their small study who had never tested positive for COVID-19 but who were having symptoms of long COVID nevertheless showed evidence of immune responses consistent with previous exposure.
“We estimate that millions of people got COVID in the U.S. during the first year of the pandemic and then developed long COVID, yet they did not get a positive COVID diagnosis because of testing limitations,” Igor J. Koralnik, MD, of Northwestern Medicine Comprehensive COVID-19 Center in Chicago, said in an interview.
He noted that many post-COVID-19 clinics in the United States don’t accept people with long COVID symptoms who do not have a positive test result.
Patients with long COVID symptoms but without laboratory evidence of prior infection, “who have often been rejected and stigmatized, should feel vindicated by the results of our study,” Dr. Koralnik said.
“We think that those patients deserve the same clinical care as those with a positive test, as well as inclusion in research studies. This is what we are doing at Northwestern Medicine’s Comprehensive COVID[-19] Center,” Dr. Koralnik added.
The study was published online in the journal Neurology: Neuroimmunology & Neuroinflammation.
Delayed care
The researchers measured SARS-CoV-2-specific humoral and cell-mediated immune responses against nucleocapsid protein and spike proteins, which indicate a prior COVID-19 infection, in 29 patients with post-viral syndrome after suspected COVID-19, including neurologic symptoms such as cognitive impairment, headache, and fatigue, but who did not have a confirmed positive COVID-19 test.
They did the same in 32 age- and sex-matched COVID long haulers with confirmed Neuro-PASC and 18 healthy controls with none of the symptoms of long COVID and no known exposure to SARS-CoV-2 or positive test result.
They found that 12 of the 29 patients (41%) with post-viral syndrome (but no positive COVID-19 test) had detectable humoral and cellular immune responses consistent with prior exposure to SARS-CoV-2. Three-quarters harbored antinucleocapsid and 50% harbored antispike responses.
“Our data suggest that at least 4 million people with post-viral syndrome similar to long COVID may indeed have detectable immune responses to support a COVID diagnosis,” Dr. Koralnik said in a news release.
The 12 patients with post-viral syndrome but without a confirmed COVID-19 test had neurologic symptoms similar to those of patients with confirmed Neuro-PASC.
However, lack of a confirmed COVID-19 diagnosis likely contributed to the 5-month delay in the median time from symptom onset to clinic visit, the researchers said. They were evaluated at a median of 10.7 months vs. 5.4 months for Neuro-PASC patients.
Dr. Koralnik said in an interview that the “most important take-home message” of the study is that patients with post-viral syndrome often present with clinical manifestations similar to those of confirmed patients with Neuro-PASC, suggesting that a positive result by commercially available SARS-CoV-2 diagnostic test should not be a prerequisite for accessing care.
Patients with post-viral syndrome may benefit from the same clinical care as confirmed patients with Neuro-PASC, and the absence of a positive SARS-CoV-2 test should not preclude or delay treatment, he added.
A version of this article first appeared on Medscape.com .
This article was updated 8/28/23.
FROM NEUROLOGY, NEUROIMMUNOLOGY & NEUROINFLAMMATION
AAP’s hearing test clinical update is the first since 2009
The update is the first since 2009.
The AAP’s clinical report was published online in Pediatrics.
Charles Bower, MD, with the department of otolaryngology at Arkansas Children’s Hospital in Little Rock, led the research team representing AAP’s Committee on Practice and Ambulatory Medicine, section on otolaryngology and head and neck surgery.
The report details how primary care clinicians can detect changes in hearing status by age.
Eliminating terms such as ‘failed’ or ‘impairment’
A key change in this report is that it no longer uses terms such as “loss,” “failed,” or “impairment,” “to reflect that children who are deaf or hard of hearing (D/HH) are equal, healthy, and whole,” the authors wrote.
The report’s recommendations are based on the literature and engagement with deaf and hard of hearing professionals and partner organizations, such as the National Association of the Deaf, working with the AAP Early Hearing Detection and Intervention program.
Birth to 5 a critical time
The authors noted that early medical support for hearing is especially important between birth and 5 years of age. That span is a critical time for brain and language development.
Parents and caregivers are often the first to notice a child’s inattention or erratic responses to sound, they wrote, and it’s important to address these concerns with a pediatrician even if the child has passed a newborn hearing test after birth.
Among recommendations in the update:
- All children should have an objective, evidence-based risk assessment for changes in hearing.
- Children at all ages should have prompt screening if there is clinical or caregiver concern about hearing.
- A child who screens positive for atypical hearing in one or both ears should be referred to an audiologist for diagnostic consultation and testing.
- Because standard testing for children with developmental or behavioral health conditions may be impossible or inaccurate, referral may be more appropriate to audiology for electrophysiological hearing testing using auditory brainstem response (ABR) with sedation.
- To prevent false negatives and to avoid delays in identification, access to language, and support, screening tests should not be repeated more than once before referral to audiology.
Additional recommendations
The report authors pointed out that genetic causes may affect hearing and may show up beyond the newborn period.
They wrote that congenital cytomegalovirus (cCMV) infection is the most common infectious cause of childhood sensorineural hearing change and accounts for 25% of deaf and hard of hearing children at age 4.
Meningitis and otitis media also are leading causes of a change in hearing.
Judith E.C. Lieu, MD, MSPH, professor, program director and vice-chair for education in the department of otolaryngology and head and neck surgery at Washington University in St. Louis, who was not part of the research team, said screening recommendations have not changed much in the update, but she highlighted some points.
She noted that tympanometry is not listed as a method of hearing screening in primary care.
“I agree that tympanogram is not a hearing screening. It is an adjunct to look at middle ear function, but that doesn’t necessarily mean it looks for hearing,” she said.
Dr. Lieu says she does take issue with the stated length of one of the tests in the paper. She said she is concerned that the pure-tone audiometry test for ages 4 through adolescence is listed as taking 30 minutes in a primary care setting. She said she worries that pediatricians will be put off by reading that it is a 30-minute test.
“Honestly, in my experience, it doesn’t take 30 minutes. Maybe 10 minutes,” she said. “I don’t know any pediatrician who could devote 30 minutes to one screening test.”
Development milestones have been adjusted
Also different in these recommendations are the developmental and speech milestones updated according to the most recent AAP information, Dr. Lieu said. Though the new milestones don’t change by much, they are important to note, she said, such as updated guidance on when to be concerned about speech delay.
She said she wished the guidance included more about hearing loss in older children.
The report authors stated that about 1 to 3 per 1,000 children have atypical hearing at birth and similar numbers become deaf or hard of hearing later in childhood.
But Dr. Lieu says that statistic may give the wrong impression about frequency of atypical hearing.
“Hearing loss increases during childhood,” she pointed out. “By the time they hit about age 18, about 15% of kids have some kind of hearing loss.”
“I don’t think it’s made clear to pediatricians that this is not 1 or 2 in a thousand children – this happens much more frequently,” she said.
The report authors and Dr. Lieu report no relevant financial relationships.
The update is the first since 2009.
The AAP’s clinical report was published online in Pediatrics.
Charles Bower, MD, with the department of otolaryngology at Arkansas Children’s Hospital in Little Rock, led the research team representing AAP’s Committee on Practice and Ambulatory Medicine, section on otolaryngology and head and neck surgery.
The report details how primary care clinicians can detect changes in hearing status by age.
Eliminating terms such as ‘failed’ or ‘impairment’
A key change in this report is that it no longer uses terms such as “loss,” “failed,” or “impairment,” “to reflect that children who are deaf or hard of hearing (D/HH) are equal, healthy, and whole,” the authors wrote.
The report’s recommendations are based on the literature and engagement with deaf and hard of hearing professionals and partner organizations, such as the National Association of the Deaf, working with the AAP Early Hearing Detection and Intervention program.
Birth to 5 a critical time
The authors noted that early medical support for hearing is especially important between birth and 5 years of age. That span is a critical time for brain and language development.
Parents and caregivers are often the first to notice a child’s inattention or erratic responses to sound, they wrote, and it’s important to address these concerns with a pediatrician even if the child has passed a newborn hearing test after birth.
Among recommendations in the update:
- All children should have an objective, evidence-based risk assessment for changes in hearing.
- Children at all ages should have prompt screening if there is clinical or caregiver concern about hearing.
- A child who screens positive for atypical hearing in one or both ears should be referred to an audiologist for diagnostic consultation and testing.
- Because standard testing for children with developmental or behavioral health conditions may be impossible or inaccurate, referral may be more appropriate to audiology for electrophysiological hearing testing using auditory brainstem response (ABR) with sedation.
- To prevent false negatives and to avoid delays in identification, access to language, and support, screening tests should not be repeated more than once before referral to audiology.
Additional recommendations
The report authors pointed out that genetic causes may affect hearing and may show up beyond the newborn period.
They wrote that congenital cytomegalovirus (cCMV) infection is the most common infectious cause of childhood sensorineural hearing change and accounts for 25% of deaf and hard of hearing children at age 4.
Meningitis and otitis media also are leading causes of a change in hearing.
Judith E.C. Lieu, MD, MSPH, professor, program director and vice-chair for education in the department of otolaryngology and head and neck surgery at Washington University in St. Louis, who was not part of the research team, said screening recommendations have not changed much in the update, but she highlighted some points.
She noted that tympanometry is not listed as a method of hearing screening in primary care.
“I agree that tympanogram is not a hearing screening. It is an adjunct to look at middle ear function, but that doesn’t necessarily mean it looks for hearing,” she said.
Dr. Lieu says she does take issue with the stated length of one of the tests in the paper. She said she is concerned that the pure-tone audiometry test for ages 4 through adolescence is listed as taking 30 minutes in a primary care setting. She said she worries that pediatricians will be put off by reading that it is a 30-minute test.
“Honestly, in my experience, it doesn’t take 30 minutes. Maybe 10 minutes,” she said. “I don’t know any pediatrician who could devote 30 minutes to one screening test.”
Development milestones have been adjusted
Also different in these recommendations are the developmental and speech milestones updated according to the most recent AAP information, Dr. Lieu said. Though the new milestones don’t change by much, they are important to note, she said, such as updated guidance on when to be concerned about speech delay.
She said she wished the guidance included more about hearing loss in older children.
The report authors stated that about 1 to 3 per 1,000 children have atypical hearing at birth and similar numbers become deaf or hard of hearing later in childhood.
But Dr. Lieu says that statistic may give the wrong impression about frequency of atypical hearing.
“Hearing loss increases during childhood,” she pointed out. “By the time they hit about age 18, about 15% of kids have some kind of hearing loss.”
“I don’t think it’s made clear to pediatricians that this is not 1 or 2 in a thousand children – this happens much more frequently,” she said.
The report authors and Dr. Lieu report no relevant financial relationships.
The update is the first since 2009.
The AAP’s clinical report was published online in Pediatrics.
Charles Bower, MD, with the department of otolaryngology at Arkansas Children’s Hospital in Little Rock, led the research team representing AAP’s Committee on Practice and Ambulatory Medicine, section on otolaryngology and head and neck surgery.
The report details how primary care clinicians can detect changes in hearing status by age.
Eliminating terms such as ‘failed’ or ‘impairment’
A key change in this report is that it no longer uses terms such as “loss,” “failed,” or “impairment,” “to reflect that children who are deaf or hard of hearing (D/HH) are equal, healthy, and whole,” the authors wrote.
The report’s recommendations are based on the literature and engagement with deaf and hard of hearing professionals and partner organizations, such as the National Association of the Deaf, working with the AAP Early Hearing Detection and Intervention program.
Birth to 5 a critical time
The authors noted that early medical support for hearing is especially important between birth and 5 years of age. That span is a critical time for brain and language development.
Parents and caregivers are often the first to notice a child’s inattention or erratic responses to sound, they wrote, and it’s important to address these concerns with a pediatrician even if the child has passed a newborn hearing test after birth.
Among recommendations in the update:
- All children should have an objective, evidence-based risk assessment for changes in hearing.
- Children at all ages should have prompt screening if there is clinical or caregiver concern about hearing.
- A child who screens positive for atypical hearing in one or both ears should be referred to an audiologist for diagnostic consultation and testing.
- Because standard testing for children with developmental or behavioral health conditions may be impossible or inaccurate, referral may be more appropriate to audiology for electrophysiological hearing testing using auditory brainstem response (ABR) with sedation.
- To prevent false negatives and to avoid delays in identification, access to language, and support, screening tests should not be repeated more than once before referral to audiology.
Additional recommendations
The report authors pointed out that genetic causes may affect hearing and may show up beyond the newborn period.
They wrote that congenital cytomegalovirus (cCMV) infection is the most common infectious cause of childhood sensorineural hearing change and accounts for 25% of deaf and hard of hearing children at age 4.
Meningitis and otitis media also are leading causes of a change in hearing.
Judith E.C. Lieu, MD, MSPH, professor, program director and vice-chair for education in the department of otolaryngology and head and neck surgery at Washington University in St. Louis, who was not part of the research team, said screening recommendations have not changed much in the update, but she highlighted some points.
She noted that tympanometry is not listed as a method of hearing screening in primary care.
“I agree that tympanogram is not a hearing screening. It is an adjunct to look at middle ear function, but that doesn’t necessarily mean it looks for hearing,” she said.
Dr. Lieu says she does take issue with the stated length of one of the tests in the paper. She said she is concerned that the pure-tone audiometry test for ages 4 through adolescence is listed as taking 30 minutes in a primary care setting. She said she worries that pediatricians will be put off by reading that it is a 30-minute test.
“Honestly, in my experience, it doesn’t take 30 minutes. Maybe 10 minutes,” she said. “I don’t know any pediatrician who could devote 30 minutes to one screening test.”
Development milestones have been adjusted
Also different in these recommendations are the developmental and speech milestones updated according to the most recent AAP information, Dr. Lieu said. Though the new milestones don’t change by much, they are important to note, she said, such as updated guidance on when to be concerned about speech delay.
She said she wished the guidance included more about hearing loss in older children.
The report authors stated that about 1 to 3 per 1,000 children have atypical hearing at birth and similar numbers become deaf or hard of hearing later in childhood.
But Dr. Lieu says that statistic may give the wrong impression about frequency of atypical hearing.
“Hearing loss increases during childhood,” she pointed out. “By the time they hit about age 18, about 15% of kids have some kind of hearing loss.”
“I don’t think it’s made clear to pediatricians that this is not 1 or 2 in a thousand children – this happens much more frequently,” she said.
The report authors and Dr. Lieu report no relevant financial relationships.
FROM PEDIATRICS
National Practitioner Data Bank should go public, group says
arguing that extra public scrutiny could pressure state medical boards to be more aggressive watchdogs.
Public Citizen’s report includes an analysis of how frequently medical boards sanctioned physicians in 2019, 2020, and 2021. These sanctions include license revocations, suspensions, voluntary surrenders of licenses, and limitations on practice while under investigation.
The report used data from the National Practitioner Data Bank (NPDB), a federal repository of reports about state licensure, discipline, and certification actions as well as medical malpractice payments. The database is closed to the public, but hospitals, malpractice insurers, and investigators can query it.
According to Public Citizen’s calculations, states most likely to take serious disciplinary action against physicians were:
- Michigan: 1.74 serious disciplinary actions per 1,000 physicians per year
- Ohio: 1.61
- North Dakota: 1.60
- Colorado: 1.55
- Arizona: 1.53
- The states least likely to do so were:
- Nevada: 0.24 serious disciplinary actions per 1,000 physicians per year
- New Hampshire: 0.25
- Georgia: 0.27
- Indiana: 0.28
- Nebraska: 0.32
- California, the largest U.S. state by both population and number of physicians, landed near the middle, ranking 27th with a rate of 0.83 serious actions per 1,000 physicians, Public Citizen said.
“There is no evidence that physicians in any state are, overall, more or less likely to be incompetent or miscreant than the physicians in any other state,” said Robert Oshel, PhD, a former NPDB associate director for research and an author of the report.
The differences instead reflect variations in boards’ enforcement of medical practice laws, domination of licensing boards by physicians, and inadequate budgets, he noted.
Public Citizen said Congress should change federal law to let members of the public get information from the NPDB to do a background check on physicians whom they are considering seeing or are already seeing. This would not only help individuals but also would spur state licensing boards to do their own checks with the NPDB, the group said.
“If licensing boards routinely queried the NPDB, they would not be faulted by the public and state legislators for not knowing about malpractice payments or disciplinary actions affecting their licensees and therefore not taking reasonable actions concerning their licensees found to have poor records,” the report said.
Questioning NPDB access for consumers
Michelle Mello, JD, PhD, a professor of law and health policy at Stanford (Calif.) University, has studied the current applications of the NPDB. In 2019, she published an article in The New England Journal of Medicine examining changes in practice patterns for clinicians who faced multiple malpractice claims.
Dr. Mello questioned what benefit consumers would get from direct access to the NPDB’s information.
“It provides almost no context for the information it reports, making it even harder for patients to make sense of what they see there,” Dr. Mello said in an interview.
Hospitals are already required to routinely query the NPDB. This legal requirement should be expanded to include licensing boards, which the report called “the last line of defense for the public from incompetent and miscreant physicians,” Public Citizen said.
“Ideally, this amendment should include free continuous query access by medical boards for all their licensees,” the report said. “In the absence of any action by Congress, individual state legislatures should require their licensing boards to query all their licensees or enroll in continuous query, as a few states already do.”
The Federation of State Medical Boards agreed with some of the other suggestions Public Citizen offered in the report. The two concur on the need for increased funding to state medical boards to ensure that they have adequate resources and staffing to fulfill their duties, FSMB said in a statement.
But FSMB disagreed with Public Citizens’ approach to ranking boards, saying it could mislead. The report lacks context about how boards’ funding and authority vary, Humayun Chaudhry, DO, FSMB’s chief executive officer, said. He also questioned the decision to focus only on serious disciplinary actions.
“The Public Citizen report does not take into account the wide range of disciplinary steps boards can take such as letters of reprimand or fines, which are often enough to stop problem behaviors – preempting further problems in the future,” Dr. Chaudhry said.
D.C. gets worst rating
The District of Columbia earned the worst mark in the Public Citizen ranking, holding the 51st spot, the same place it held in the group’s similar ranking on actions taken in the 2017-2019 period. There were 0.19 serious disciplinary actions per 1,000 physicians a year in Washington, Public Citizen said.
In an email to this news organization, Dr. Oshel said that the Public Citizen analysis focused on the number of licensed physicians in each state and D.C. that can be obtained and compared reliably. It avoided using the term “practicing physicians” owing in part to doubts about the reliability of these counts, he said.
As many as 20% of physicians nationwide are focused primarily on work outside of clinical care, Dr. Oshel estimated. In D.C., perhaps 40% of physicians may fall into this category. Of the more than 13,700 physicians licensed in D.C., there may be only about 8,126 actively practicing, according to Dr. Oshel.
But even using that lower estimate of practicing physicians would only raise D.C.’s ranking to 46, signaling a need for stepped-up enforcement, Dr. Oshel said.
“[Whether it’s] 46th or 51st, both are bad,” Dr. Oshel said.
A version of this article first appeared on Medscape.com.
arguing that extra public scrutiny could pressure state medical boards to be more aggressive watchdogs.
Public Citizen’s report includes an analysis of how frequently medical boards sanctioned physicians in 2019, 2020, and 2021. These sanctions include license revocations, suspensions, voluntary surrenders of licenses, and limitations on practice while under investigation.
The report used data from the National Practitioner Data Bank (NPDB), a federal repository of reports about state licensure, discipline, and certification actions as well as medical malpractice payments. The database is closed to the public, but hospitals, malpractice insurers, and investigators can query it.
According to Public Citizen’s calculations, states most likely to take serious disciplinary action against physicians were:
- Michigan: 1.74 serious disciplinary actions per 1,000 physicians per year
- Ohio: 1.61
- North Dakota: 1.60
- Colorado: 1.55
- Arizona: 1.53
- The states least likely to do so were:
- Nevada: 0.24 serious disciplinary actions per 1,000 physicians per year
- New Hampshire: 0.25
- Georgia: 0.27
- Indiana: 0.28
- Nebraska: 0.32
- California, the largest U.S. state by both population and number of physicians, landed near the middle, ranking 27th with a rate of 0.83 serious actions per 1,000 physicians, Public Citizen said.
“There is no evidence that physicians in any state are, overall, more or less likely to be incompetent or miscreant than the physicians in any other state,” said Robert Oshel, PhD, a former NPDB associate director for research and an author of the report.
The differences instead reflect variations in boards’ enforcement of medical practice laws, domination of licensing boards by physicians, and inadequate budgets, he noted.
Public Citizen said Congress should change federal law to let members of the public get information from the NPDB to do a background check on physicians whom they are considering seeing or are already seeing. This would not only help individuals but also would spur state licensing boards to do their own checks with the NPDB, the group said.
“If licensing boards routinely queried the NPDB, they would not be faulted by the public and state legislators for not knowing about malpractice payments or disciplinary actions affecting their licensees and therefore not taking reasonable actions concerning their licensees found to have poor records,” the report said.
Questioning NPDB access for consumers
Michelle Mello, JD, PhD, a professor of law and health policy at Stanford (Calif.) University, has studied the current applications of the NPDB. In 2019, she published an article in The New England Journal of Medicine examining changes in practice patterns for clinicians who faced multiple malpractice claims.
Dr. Mello questioned what benefit consumers would get from direct access to the NPDB’s information.
“It provides almost no context for the information it reports, making it even harder for patients to make sense of what they see there,” Dr. Mello said in an interview.
Hospitals are already required to routinely query the NPDB. This legal requirement should be expanded to include licensing boards, which the report called “the last line of defense for the public from incompetent and miscreant physicians,” Public Citizen said.
“Ideally, this amendment should include free continuous query access by medical boards for all their licensees,” the report said. “In the absence of any action by Congress, individual state legislatures should require their licensing boards to query all their licensees or enroll in continuous query, as a few states already do.”
The Federation of State Medical Boards agreed with some of the other suggestions Public Citizen offered in the report. The two concur on the need for increased funding to state medical boards to ensure that they have adequate resources and staffing to fulfill their duties, FSMB said in a statement.
But FSMB disagreed with Public Citizens’ approach to ranking boards, saying it could mislead. The report lacks context about how boards’ funding and authority vary, Humayun Chaudhry, DO, FSMB’s chief executive officer, said. He also questioned the decision to focus only on serious disciplinary actions.
“The Public Citizen report does not take into account the wide range of disciplinary steps boards can take such as letters of reprimand or fines, which are often enough to stop problem behaviors – preempting further problems in the future,” Dr. Chaudhry said.
D.C. gets worst rating
The District of Columbia earned the worst mark in the Public Citizen ranking, holding the 51st spot, the same place it held in the group’s similar ranking on actions taken in the 2017-2019 period. There were 0.19 serious disciplinary actions per 1,000 physicians a year in Washington, Public Citizen said.
In an email to this news organization, Dr. Oshel said that the Public Citizen analysis focused on the number of licensed physicians in each state and D.C. that can be obtained and compared reliably. It avoided using the term “practicing physicians” owing in part to doubts about the reliability of these counts, he said.
As many as 20% of physicians nationwide are focused primarily on work outside of clinical care, Dr. Oshel estimated. In D.C., perhaps 40% of physicians may fall into this category. Of the more than 13,700 physicians licensed in D.C., there may be only about 8,126 actively practicing, according to Dr. Oshel.
But even using that lower estimate of practicing physicians would only raise D.C.’s ranking to 46, signaling a need for stepped-up enforcement, Dr. Oshel said.
“[Whether it’s] 46th or 51st, both are bad,” Dr. Oshel said.
A version of this article first appeared on Medscape.com.
arguing that extra public scrutiny could pressure state medical boards to be more aggressive watchdogs.
Public Citizen’s report includes an analysis of how frequently medical boards sanctioned physicians in 2019, 2020, and 2021. These sanctions include license revocations, suspensions, voluntary surrenders of licenses, and limitations on practice while under investigation.
The report used data from the National Practitioner Data Bank (NPDB), a federal repository of reports about state licensure, discipline, and certification actions as well as medical malpractice payments. The database is closed to the public, but hospitals, malpractice insurers, and investigators can query it.
According to Public Citizen’s calculations, states most likely to take serious disciplinary action against physicians were:
- Michigan: 1.74 serious disciplinary actions per 1,000 physicians per year
- Ohio: 1.61
- North Dakota: 1.60
- Colorado: 1.55
- Arizona: 1.53
- The states least likely to do so were:
- Nevada: 0.24 serious disciplinary actions per 1,000 physicians per year
- New Hampshire: 0.25
- Georgia: 0.27
- Indiana: 0.28
- Nebraska: 0.32
- California, the largest U.S. state by both population and number of physicians, landed near the middle, ranking 27th with a rate of 0.83 serious actions per 1,000 physicians, Public Citizen said.
“There is no evidence that physicians in any state are, overall, more or less likely to be incompetent or miscreant than the physicians in any other state,” said Robert Oshel, PhD, a former NPDB associate director for research and an author of the report.
The differences instead reflect variations in boards’ enforcement of medical practice laws, domination of licensing boards by physicians, and inadequate budgets, he noted.
Public Citizen said Congress should change federal law to let members of the public get information from the NPDB to do a background check on physicians whom they are considering seeing or are already seeing. This would not only help individuals but also would spur state licensing boards to do their own checks with the NPDB, the group said.
“If licensing boards routinely queried the NPDB, they would not be faulted by the public and state legislators for not knowing about malpractice payments or disciplinary actions affecting their licensees and therefore not taking reasonable actions concerning their licensees found to have poor records,” the report said.
Questioning NPDB access for consumers
Michelle Mello, JD, PhD, a professor of law and health policy at Stanford (Calif.) University, has studied the current applications of the NPDB. In 2019, she published an article in The New England Journal of Medicine examining changes in practice patterns for clinicians who faced multiple malpractice claims.
Dr. Mello questioned what benefit consumers would get from direct access to the NPDB’s information.
“It provides almost no context for the information it reports, making it even harder for patients to make sense of what they see there,” Dr. Mello said in an interview.
Hospitals are already required to routinely query the NPDB. This legal requirement should be expanded to include licensing boards, which the report called “the last line of defense for the public from incompetent and miscreant physicians,” Public Citizen said.
“Ideally, this amendment should include free continuous query access by medical boards for all their licensees,” the report said. “In the absence of any action by Congress, individual state legislatures should require their licensing boards to query all their licensees or enroll in continuous query, as a few states already do.”
The Federation of State Medical Boards agreed with some of the other suggestions Public Citizen offered in the report. The two concur on the need for increased funding to state medical boards to ensure that they have adequate resources and staffing to fulfill their duties, FSMB said in a statement.
But FSMB disagreed with Public Citizens’ approach to ranking boards, saying it could mislead. The report lacks context about how boards’ funding and authority vary, Humayun Chaudhry, DO, FSMB’s chief executive officer, said. He also questioned the decision to focus only on serious disciplinary actions.
“The Public Citizen report does not take into account the wide range of disciplinary steps boards can take such as letters of reprimand or fines, which are often enough to stop problem behaviors – preempting further problems in the future,” Dr. Chaudhry said.
D.C. gets worst rating
The District of Columbia earned the worst mark in the Public Citizen ranking, holding the 51st spot, the same place it held in the group’s similar ranking on actions taken in the 2017-2019 period. There were 0.19 serious disciplinary actions per 1,000 physicians a year in Washington, Public Citizen said.
In an email to this news organization, Dr. Oshel said that the Public Citizen analysis focused on the number of licensed physicians in each state and D.C. that can be obtained and compared reliably. It avoided using the term “practicing physicians” owing in part to doubts about the reliability of these counts, he said.
As many as 20% of physicians nationwide are focused primarily on work outside of clinical care, Dr. Oshel estimated. In D.C., perhaps 40% of physicians may fall into this category. Of the more than 13,700 physicians licensed in D.C., there may be only about 8,126 actively practicing, according to Dr. Oshel.
But even using that lower estimate of practicing physicians would only raise D.C.’s ranking to 46, signaling a need for stepped-up enforcement, Dr. Oshel said.
“[Whether it’s] 46th or 51st, both are bad,” Dr. Oshel said.
A version of this article first appeared on Medscape.com.
‘Patients fail’ despite benefits of sustained weight loss
Don’t look for the publication of a study detailing the probability of blood pressure reduction to normotensive among adults with hypertension who aren’t offered pharmacotherapy in a JAMA journal. It’s not because hypertension doesn’t respond to intentional behavior change. On the contrary, it absolutely does, but when it comes to hypertension, physicians don’t require patients to fail to manage their hypertension through personal responsibility before medications are discussed and involved.
Not so, of course, with obesity.
A few weeks ago a paper was published in JAMA Network Open entitled “Probability of 5% or greater weight loss or BMI reduction to healthy weight among adults with overweight or obesity,” which authors, peer reviewers, and editors deemed worthy of publication. Now, to be fair, it might be worthy of publication if the call to action and thrust of the paper was to chastise physicians for not offering patients effective treatments; the medical education system for failing to teach physicians how to effectively manage obesity; or, if medication is being offered, addressing the barriers to its use. Instead, the main thrust was that patients are failing to help themselves despite the known health benefits of sustained weight loss.
It’s not at all surprising that, despite known benefits, sustained weight loss without pharmacotherapy or surgery is elusive. Just as with virtually every other chronic noncommunicable disease with lifestyle levers, intentional behavior change as treatment – which, by definition for chronic diseases, needs to be employed in perpetuity – requires wide-ranging degrees of privilege and is not a reasonable expectation. And if outcomes from the FREEE trial are applicable broadly, this may be true even if the behavior change required is minimal, the cost is free, and the motivation is large.
The FREEE trial studied whether cost had a role to play in why so many people, even after a myocardial infarction, don’t follow through with the simplest of intentional behavior changes – taking prescribed medications – by providing free medications known to reduce the risk of having a second MI to study participants who had just suffered an MI.
Results showed that, although the group receiving free medications were taking more of them than the group that had a copay for them, at 1.5 years post-MI, only 41% of those receiving all their medications for free were taking them.
And what of those who have a copay? This study found that fewer than 30% of Medicare beneficiaries 65-74 years of age who were hospitalized for heart attacks filled their new statin prescriptions within 90 days of discharge. That the vast majority of patients who’d had actual heart attacks didn’t even take on the behavior change of simply filling their prescription for, let alone taking, a medication shown to reduce their risk of having another heart attack, speaks to the folly of believing that knowledge drives behavior change.
The message is that And yet here we have a paper that concludes with the inference of surprise that few people, without treatment, lost clinically meaningful amounts of weight “despite the known benefits of clinically meaningful weight loss.”
While this paper does suggest in passing that yes, maybe we should offer effective treatments to patients with obesity, medicine needs to stop framing obesity as some surprising personal-responsibility knowledge gap and instead focus on the real problems at hand: the barriers to physicians treating obesity as they do every other chronic noncommunicable disease; why, unlike hypertension, for example, primary care providers are generally not well trained in its effective management; and why those who aren’t, despite obesity’s prevalence and impact, don’t see it as worthwhile to go out of their way to learn.
Dr. Freedhoff is an associate professor in the department of family medicine at the University of Ottawa (Ont.) and medical director of the Bariatric Medical Institute, also in Ottawa. He reported conflicts of interest with Constant Health, Novo Nordisk, and Weighty Matters.
A version of this article first appeared on Medscape.com.
Don’t look for the publication of a study detailing the probability of blood pressure reduction to normotensive among adults with hypertension who aren’t offered pharmacotherapy in a JAMA journal. It’s not because hypertension doesn’t respond to intentional behavior change. On the contrary, it absolutely does, but when it comes to hypertension, physicians don’t require patients to fail to manage their hypertension through personal responsibility before medications are discussed and involved.
Not so, of course, with obesity.
A few weeks ago a paper was published in JAMA Network Open entitled “Probability of 5% or greater weight loss or BMI reduction to healthy weight among adults with overweight or obesity,” which authors, peer reviewers, and editors deemed worthy of publication. Now, to be fair, it might be worthy of publication if the call to action and thrust of the paper was to chastise physicians for not offering patients effective treatments; the medical education system for failing to teach physicians how to effectively manage obesity; or, if medication is being offered, addressing the barriers to its use. Instead, the main thrust was that patients are failing to help themselves despite the known health benefits of sustained weight loss.
It’s not at all surprising that, despite known benefits, sustained weight loss without pharmacotherapy or surgery is elusive. Just as with virtually every other chronic noncommunicable disease with lifestyle levers, intentional behavior change as treatment – which, by definition for chronic diseases, needs to be employed in perpetuity – requires wide-ranging degrees of privilege and is not a reasonable expectation. And if outcomes from the FREEE trial are applicable broadly, this may be true even if the behavior change required is minimal, the cost is free, and the motivation is large.
The FREEE trial studied whether cost had a role to play in why so many people, even after a myocardial infarction, don’t follow through with the simplest of intentional behavior changes – taking prescribed medications – by providing free medications known to reduce the risk of having a second MI to study participants who had just suffered an MI.
Results showed that, although the group receiving free medications were taking more of them than the group that had a copay for them, at 1.5 years post-MI, only 41% of those receiving all their medications for free were taking them.
And what of those who have a copay? This study found that fewer than 30% of Medicare beneficiaries 65-74 years of age who were hospitalized for heart attacks filled their new statin prescriptions within 90 days of discharge. That the vast majority of patients who’d had actual heart attacks didn’t even take on the behavior change of simply filling their prescription for, let alone taking, a medication shown to reduce their risk of having another heart attack, speaks to the folly of believing that knowledge drives behavior change.
The message is that And yet here we have a paper that concludes with the inference of surprise that few people, without treatment, lost clinically meaningful amounts of weight “despite the known benefits of clinically meaningful weight loss.”
While this paper does suggest in passing that yes, maybe we should offer effective treatments to patients with obesity, medicine needs to stop framing obesity as some surprising personal-responsibility knowledge gap and instead focus on the real problems at hand: the barriers to physicians treating obesity as they do every other chronic noncommunicable disease; why, unlike hypertension, for example, primary care providers are generally not well trained in its effective management; and why those who aren’t, despite obesity’s prevalence and impact, don’t see it as worthwhile to go out of their way to learn.
Dr. Freedhoff is an associate professor in the department of family medicine at the University of Ottawa (Ont.) and medical director of the Bariatric Medical Institute, also in Ottawa. He reported conflicts of interest with Constant Health, Novo Nordisk, and Weighty Matters.
A version of this article first appeared on Medscape.com.
Don’t look for the publication of a study detailing the probability of blood pressure reduction to normotensive among adults with hypertension who aren’t offered pharmacotherapy in a JAMA journal. It’s not because hypertension doesn’t respond to intentional behavior change. On the contrary, it absolutely does, but when it comes to hypertension, physicians don’t require patients to fail to manage their hypertension through personal responsibility before medications are discussed and involved.
Not so, of course, with obesity.
A few weeks ago a paper was published in JAMA Network Open entitled “Probability of 5% or greater weight loss or BMI reduction to healthy weight among adults with overweight or obesity,” which authors, peer reviewers, and editors deemed worthy of publication. Now, to be fair, it might be worthy of publication if the call to action and thrust of the paper was to chastise physicians for not offering patients effective treatments; the medical education system for failing to teach physicians how to effectively manage obesity; or, if medication is being offered, addressing the barriers to its use. Instead, the main thrust was that patients are failing to help themselves despite the known health benefits of sustained weight loss.
It’s not at all surprising that, despite known benefits, sustained weight loss without pharmacotherapy or surgery is elusive. Just as with virtually every other chronic noncommunicable disease with lifestyle levers, intentional behavior change as treatment – which, by definition for chronic diseases, needs to be employed in perpetuity – requires wide-ranging degrees of privilege and is not a reasonable expectation. And if outcomes from the FREEE trial are applicable broadly, this may be true even if the behavior change required is minimal, the cost is free, and the motivation is large.
The FREEE trial studied whether cost had a role to play in why so many people, even after a myocardial infarction, don’t follow through with the simplest of intentional behavior changes – taking prescribed medications – by providing free medications known to reduce the risk of having a second MI to study participants who had just suffered an MI.
Results showed that, although the group receiving free medications were taking more of them than the group that had a copay for them, at 1.5 years post-MI, only 41% of those receiving all their medications for free were taking them.
And what of those who have a copay? This study found that fewer than 30% of Medicare beneficiaries 65-74 years of age who were hospitalized for heart attacks filled their new statin prescriptions within 90 days of discharge. That the vast majority of patients who’d had actual heart attacks didn’t even take on the behavior change of simply filling their prescription for, let alone taking, a medication shown to reduce their risk of having another heart attack, speaks to the folly of believing that knowledge drives behavior change.
The message is that And yet here we have a paper that concludes with the inference of surprise that few people, without treatment, lost clinically meaningful amounts of weight “despite the known benefits of clinically meaningful weight loss.”
While this paper does suggest in passing that yes, maybe we should offer effective treatments to patients with obesity, medicine needs to stop framing obesity as some surprising personal-responsibility knowledge gap and instead focus on the real problems at hand: the barriers to physicians treating obesity as they do every other chronic noncommunicable disease; why, unlike hypertension, for example, primary care providers are generally not well trained in its effective management; and why those who aren’t, despite obesity’s prevalence and impact, don’t see it as worthwhile to go out of their way to learn.
Dr. Freedhoff is an associate professor in the department of family medicine at the University of Ottawa (Ont.) and medical director of the Bariatric Medical Institute, also in Ottawa. He reported conflicts of interest with Constant Health, Novo Nordisk, and Weighty Matters.
A version of this article first appeared on Medscape.com.
Liraglutide fixes learning limit tied to insulin resistance
A single injection of the GLP-1 receptor agonist liraglutide led to short-term normalization of associative learning in people with obesity and insulin resistance, a finding that suggests say the authors of a recent report in Nature Metabolism.
“We demonstrated that dopamine-driven associative learning about external sensory cues crucially depends on metabolic signaling,” said Marc Tittgemeyer, PhD, professor at the Max Planck Institute for Metabolism Research in Cologne, Germany, and senior author of the study. Study participants with impaired insulin sensitivity “exhibited a reduced amplitude of behavioral updating that was normalized” by a single subcutaneous injection of 0.6 mg of liraglutide (the starting daily dose for liraglutide for weight loss, available as Saxenda, Novo Nordisk) given the evening before testing.
The findings, from 30 adults with normal insulin sensitivity and normal weight and 24 adults with impaired insulin sensitivity and obesity, suggest that metabolic signals, particularly ones that promote energy restoration in a setting of energy deprivation caused by insulin or a glucagon-like peptide-1 (GLP-1) receptor agonist, “profoundly influence neuronal processing,” said Dr. Tittgemeyer. The findings suggest that impaired metabolic signaling such as occurs with insulin resistance in people with obesity can cause deficiencies in associative learning.
‘Liraglutide can normalize learning of associations’
“We show that in people with obesity, disrupted circuit mechanisms lead to impaired learning about sensory associations,” Dr. Tittgemeyer said in an interview. “The information provided by sensory systems that the brain must interpret to select a behavioral response are ‘off tune’ ” in these individuals.
“This is rather consequential for understanding food-intake behaviors. Modern obesity treatments, such as liraglutide, can normalize learning of associations and thereby render people susceptible again for sensory signals and make them more prone to react to subliminal interactions, such as weight-normalizing diets and conscious eating,” he added.
The normalization in associative learning that one dose of liraglutide produced in people with obesity “fits with studies showing that these drugs restore a normal feeling of satiety, causing people to eat less and therefore lose weight,” he explained.
Dr. Tittgemeyer noted that this effect is likely shared by other agents in the GLP-1 receptor agonist class, such as semaglutide (Ozempic, Wegovy, Novo Nordisk) but is likely not an effect when agents agonize receptors to other nutrient-stimulated hormones such as glucagon and the glucose-dependent insulinotropic polypeptide.
The findings “show that liraglutide restores associative learning in participants with greater insulin resistance,” a “highly relevant” discovery, commented Nils B. Kroemer, PhD, head of the section of medical psychology at the University of Bonn, Germany, who was not involved with this research, in a written statement.
The study run by Dr. Tittgemeyer and his associates included 54 healthy adult volunteers whom they assessed for insulin sensitivity with their homeostasis model assessment of insulin resistance. The researchers divided the cohort into groups; one group included 24 people with impaired insulin sensitivity, and one included 30 with normal insulin sensitivity. The average body mass index (BMI) of the normal sensitivity group was about 24 kg/m2; in the insulin-resistant subgroup, BMI averaged about 33 kg/m2.
The associative learning task tested the ability of participants to learn associations between auditory cues (a high or low tone) and a subsequent visual outcome (a picture of a face or a house). During each associative learning session, participants also underwent functional MRI of the brain.
Liraglutide treatment leveled learning
The results showed that the learning rate was significantly lower in the subgroup with impaired insulin sensitivity, compared with those with normal insulin sensitivity following treatment with a placebo injection. This indicates a decreased adaptation of learning to predictability variations in individuals with impaired insulin sensitivity.
In contrast, treatment with a single dose of liraglutide significantly enhanced the learning rate in the group with impaired insulin sensitivity but significantly reduced the learning rate in the group with normal insulin sensitivity. Liraglutide’s effect was twice as large in the group with impaired insulin sensitivity than in the group with normal insulin sensitivity, and these opposing effects of liraglutide resulted in a convergence of the two groups’ adaptive learning rates so that there wasn’t any significant between-group difference following liraglutide treatment.
After analyzing the functional MRI data along with the learning results, the researchers concluded that liraglutide normalized learning in individuals with impaired insulin sensitivity by enhancing adaptive prediction error encoding in the brain’s ventral striatum and mesocortical projection sites.
This apparent ability of GLP-1 analogues to correct this learning deficit in people with impaired insulin sensitivity and obesity has implications regarding potential benefit for people with other pathologies characterized by impaired dopaminergic function and associated with metabolic impairments, such as psychosis, Parkinson’s disease, and depression, the researchers say.
“The fascinating thing about GLP-1 receptor agonists is that they have an additional mechanism that relates to anti-inflammatory effects, especially for alleviating cell stress,” said Dr. Tittgemeyer. “Many ongoing clinical trials are assessing their effects in neuropsychiatric diseases,” he noted.
The study received no commercial funding. Dr. Tittgemyer and most of his coauthors had no disclosures. One coauthor had several disclosures, which are detailed in the report. Dr. Kroemer had no disclosures.
A version of this article first appeared on Medscape.com.
A single injection of the GLP-1 receptor agonist liraglutide led to short-term normalization of associative learning in people with obesity and insulin resistance, a finding that suggests say the authors of a recent report in Nature Metabolism.
“We demonstrated that dopamine-driven associative learning about external sensory cues crucially depends on metabolic signaling,” said Marc Tittgemeyer, PhD, professor at the Max Planck Institute for Metabolism Research in Cologne, Germany, and senior author of the study. Study participants with impaired insulin sensitivity “exhibited a reduced amplitude of behavioral updating that was normalized” by a single subcutaneous injection of 0.6 mg of liraglutide (the starting daily dose for liraglutide for weight loss, available as Saxenda, Novo Nordisk) given the evening before testing.
The findings, from 30 adults with normal insulin sensitivity and normal weight and 24 adults with impaired insulin sensitivity and obesity, suggest that metabolic signals, particularly ones that promote energy restoration in a setting of energy deprivation caused by insulin or a glucagon-like peptide-1 (GLP-1) receptor agonist, “profoundly influence neuronal processing,” said Dr. Tittgemeyer. The findings suggest that impaired metabolic signaling such as occurs with insulin resistance in people with obesity can cause deficiencies in associative learning.
‘Liraglutide can normalize learning of associations’
“We show that in people with obesity, disrupted circuit mechanisms lead to impaired learning about sensory associations,” Dr. Tittgemeyer said in an interview. “The information provided by sensory systems that the brain must interpret to select a behavioral response are ‘off tune’ ” in these individuals.
“This is rather consequential for understanding food-intake behaviors. Modern obesity treatments, such as liraglutide, can normalize learning of associations and thereby render people susceptible again for sensory signals and make them more prone to react to subliminal interactions, such as weight-normalizing diets and conscious eating,” he added.
The normalization in associative learning that one dose of liraglutide produced in people with obesity “fits with studies showing that these drugs restore a normal feeling of satiety, causing people to eat less and therefore lose weight,” he explained.
Dr. Tittgemeyer noted that this effect is likely shared by other agents in the GLP-1 receptor agonist class, such as semaglutide (Ozempic, Wegovy, Novo Nordisk) but is likely not an effect when agents agonize receptors to other nutrient-stimulated hormones such as glucagon and the glucose-dependent insulinotropic polypeptide.
The findings “show that liraglutide restores associative learning in participants with greater insulin resistance,” a “highly relevant” discovery, commented Nils B. Kroemer, PhD, head of the section of medical psychology at the University of Bonn, Germany, who was not involved with this research, in a written statement.
The study run by Dr. Tittgemeyer and his associates included 54 healthy adult volunteers whom they assessed for insulin sensitivity with their homeostasis model assessment of insulin resistance. The researchers divided the cohort into groups; one group included 24 people with impaired insulin sensitivity, and one included 30 with normal insulin sensitivity. The average body mass index (BMI) of the normal sensitivity group was about 24 kg/m2; in the insulin-resistant subgroup, BMI averaged about 33 kg/m2.
The associative learning task tested the ability of participants to learn associations between auditory cues (a high or low tone) and a subsequent visual outcome (a picture of a face or a house). During each associative learning session, participants also underwent functional MRI of the brain.
Liraglutide treatment leveled learning
The results showed that the learning rate was significantly lower in the subgroup with impaired insulin sensitivity, compared with those with normal insulin sensitivity following treatment with a placebo injection. This indicates a decreased adaptation of learning to predictability variations in individuals with impaired insulin sensitivity.
In contrast, treatment with a single dose of liraglutide significantly enhanced the learning rate in the group with impaired insulin sensitivity but significantly reduced the learning rate in the group with normal insulin sensitivity. Liraglutide’s effect was twice as large in the group with impaired insulin sensitivity than in the group with normal insulin sensitivity, and these opposing effects of liraglutide resulted in a convergence of the two groups’ adaptive learning rates so that there wasn’t any significant between-group difference following liraglutide treatment.
After analyzing the functional MRI data along with the learning results, the researchers concluded that liraglutide normalized learning in individuals with impaired insulin sensitivity by enhancing adaptive prediction error encoding in the brain’s ventral striatum and mesocortical projection sites.
This apparent ability of GLP-1 analogues to correct this learning deficit in people with impaired insulin sensitivity and obesity has implications regarding potential benefit for people with other pathologies characterized by impaired dopaminergic function and associated with metabolic impairments, such as psychosis, Parkinson’s disease, and depression, the researchers say.
“The fascinating thing about GLP-1 receptor agonists is that they have an additional mechanism that relates to anti-inflammatory effects, especially for alleviating cell stress,” said Dr. Tittgemeyer. “Many ongoing clinical trials are assessing their effects in neuropsychiatric diseases,” he noted.
The study received no commercial funding. Dr. Tittgemyer and most of his coauthors had no disclosures. One coauthor had several disclosures, which are detailed in the report. Dr. Kroemer had no disclosures.
A version of this article first appeared on Medscape.com.
A single injection of the GLP-1 receptor agonist liraglutide led to short-term normalization of associative learning in people with obesity and insulin resistance, a finding that suggests say the authors of a recent report in Nature Metabolism.
“We demonstrated that dopamine-driven associative learning about external sensory cues crucially depends on metabolic signaling,” said Marc Tittgemeyer, PhD, professor at the Max Planck Institute for Metabolism Research in Cologne, Germany, and senior author of the study. Study participants with impaired insulin sensitivity “exhibited a reduced amplitude of behavioral updating that was normalized” by a single subcutaneous injection of 0.6 mg of liraglutide (the starting daily dose for liraglutide for weight loss, available as Saxenda, Novo Nordisk) given the evening before testing.
The findings, from 30 adults with normal insulin sensitivity and normal weight and 24 adults with impaired insulin sensitivity and obesity, suggest that metabolic signals, particularly ones that promote energy restoration in a setting of energy deprivation caused by insulin or a glucagon-like peptide-1 (GLP-1) receptor agonist, “profoundly influence neuronal processing,” said Dr. Tittgemeyer. The findings suggest that impaired metabolic signaling such as occurs with insulin resistance in people with obesity can cause deficiencies in associative learning.
‘Liraglutide can normalize learning of associations’
“We show that in people with obesity, disrupted circuit mechanisms lead to impaired learning about sensory associations,” Dr. Tittgemeyer said in an interview. “The information provided by sensory systems that the brain must interpret to select a behavioral response are ‘off tune’ ” in these individuals.
“This is rather consequential for understanding food-intake behaviors. Modern obesity treatments, such as liraglutide, can normalize learning of associations and thereby render people susceptible again for sensory signals and make them more prone to react to subliminal interactions, such as weight-normalizing diets and conscious eating,” he added.
The normalization in associative learning that one dose of liraglutide produced in people with obesity “fits with studies showing that these drugs restore a normal feeling of satiety, causing people to eat less and therefore lose weight,” he explained.
Dr. Tittgemeyer noted that this effect is likely shared by other agents in the GLP-1 receptor agonist class, such as semaglutide (Ozempic, Wegovy, Novo Nordisk) but is likely not an effect when agents agonize receptors to other nutrient-stimulated hormones such as glucagon and the glucose-dependent insulinotropic polypeptide.
The findings “show that liraglutide restores associative learning in participants with greater insulin resistance,” a “highly relevant” discovery, commented Nils B. Kroemer, PhD, head of the section of medical psychology at the University of Bonn, Germany, who was not involved with this research, in a written statement.
The study run by Dr. Tittgemeyer and his associates included 54 healthy adult volunteers whom they assessed for insulin sensitivity with their homeostasis model assessment of insulin resistance. The researchers divided the cohort into groups; one group included 24 people with impaired insulin sensitivity, and one included 30 with normal insulin sensitivity. The average body mass index (BMI) of the normal sensitivity group was about 24 kg/m2; in the insulin-resistant subgroup, BMI averaged about 33 kg/m2.
The associative learning task tested the ability of participants to learn associations between auditory cues (a high or low tone) and a subsequent visual outcome (a picture of a face or a house). During each associative learning session, participants also underwent functional MRI of the brain.
Liraglutide treatment leveled learning
The results showed that the learning rate was significantly lower in the subgroup with impaired insulin sensitivity, compared with those with normal insulin sensitivity following treatment with a placebo injection. This indicates a decreased adaptation of learning to predictability variations in individuals with impaired insulin sensitivity.
In contrast, treatment with a single dose of liraglutide significantly enhanced the learning rate in the group with impaired insulin sensitivity but significantly reduced the learning rate in the group with normal insulin sensitivity. Liraglutide’s effect was twice as large in the group with impaired insulin sensitivity than in the group with normal insulin sensitivity, and these opposing effects of liraglutide resulted in a convergence of the two groups’ adaptive learning rates so that there wasn’t any significant between-group difference following liraglutide treatment.
After analyzing the functional MRI data along with the learning results, the researchers concluded that liraglutide normalized learning in individuals with impaired insulin sensitivity by enhancing adaptive prediction error encoding in the brain’s ventral striatum and mesocortical projection sites.
This apparent ability of GLP-1 analogues to correct this learning deficit in people with impaired insulin sensitivity and obesity has implications regarding potential benefit for people with other pathologies characterized by impaired dopaminergic function and associated with metabolic impairments, such as psychosis, Parkinson’s disease, and depression, the researchers say.
“The fascinating thing about GLP-1 receptor agonists is that they have an additional mechanism that relates to anti-inflammatory effects, especially for alleviating cell stress,” said Dr. Tittgemeyer. “Many ongoing clinical trials are assessing their effects in neuropsychiatric diseases,” he noted.
The study received no commercial funding. Dr. Tittgemyer and most of his coauthors had no disclosures. One coauthor had several disclosures, which are detailed in the report. Dr. Kroemer had no disclosures.
A version of this article first appeared on Medscape.com.
FROM NATURE METABOLISM