Heart Failure

The Food and Drug Administration has approved a furosemide preparation (Furoscix, scPharmaceuticals) intended for subcutaneous self-administration by outpatients with chronic heart failure and volume overload, the company has announced.

The product is indicated for use with a SmartDose On-Body Infuser (West Pharmaceutical Services) single-use subcutaneous administration device, which affixes to the abdomen.

Olivier Le Moal/Getty Images

The infuser is loaded by the patient or caregiver with a prefilled cartridge and is programmed to deliver Furoscix 30 mg over 1 hour followed by a 4-hour infusion at 12.5 mg/h, for a total fixed dose of 80 mg, scPharmaceuticals said in a press release on the drug approval.

Furosemide, a loop diuretic and one of the world’s most frequently used drugs, is conventionally given intravenously in the hospital or orally on an outpatient basis.

The company describes its furosemide preparation, used with the infuser, as “the first and only FDA-approved subcutaneous loop diuretic that delivers [intravenous]-equivalent diuresis at home.” It has been shown to “produce similar diuresis and natriuresis compared to intravenous furosemide.”

“This marks a tremendous opportunity to improve the at-home management of worsening congestion in patients with heart failure who display reduced responsiveness to oral diuretics and require administration of [intravenous] diuretics, which typically requires admission to the hospital,” William T. Abraham, MD, said in the press release.

The FDA approval “is significant and will allow patients to be treated outside of the hospital setting,” said Dr. Abraham, of Ohio State University, Columbus, and an scPharmaceuticals board member.

The Furoscix indication doesn’t cover emergent use or use in acute pulmonary edema, nor is it meant to be used chronically “and should be replaced with oral diuretics as soon as practical,” the company states.

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

The Food and Drug Administration has approved a furosemide preparation (Furoscix, scPharmaceuticals) intended for subcutaneous self-administration by outpatients with chronic heart failure and volume overload, the company has announced.

The product is indicated for use with a SmartDose On-Body Infuser (West Pharmaceutical Services) single-use subcutaneous administration device, which affixes to the abdomen.

Olivier Le Moal/Getty Images

The infuser is loaded by the patient or caregiver with a prefilled cartridge and is programmed to deliver Furoscix 30 mg over 1 hour followed by a 4-hour infusion at 12.5 mg/h, for a total fixed dose of 80 mg, scPharmaceuticals said in a press release on the drug approval.

Furosemide, a loop diuretic and one of the world’s most frequently used drugs, is conventionally given intravenously in the hospital or orally on an outpatient basis.

The company describes its furosemide preparation, used with the infuser, as “the first and only FDA-approved subcutaneous loop diuretic that delivers [intravenous]-equivalent diuresis at home.” It has been shown to “produce similar diuresis and natriuresis compared to intravenous furosemide.”

“This marks a tremendous opportunity to improve the at-home management of worsening congestion in patients with heart failure who display reduced responsiveness to oral diuretics and require administration of [intravenous] diuretics, which typically requires admission to the hospital,” William T. Abraham, MD, said in the press release.

The FDA approval “is significant and will allow patients to be treated outside of the hospital setting,” said Dr. Abraham, of Ohio State University, Columbus, and an scPharmaceuticals board member.

The Furoscix indication doesn’t cover emergent use or use in acute pulmonary edema, nor is it meant to be used chronically “and should be replaced with oral diuretics as soon as practical,” the company states.

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

The Food and Drug Administration has approved a furosemide preparation (Furoscix, scPharmaceuticals) intended for subcutaneous self-administration by outpatients with chronic heart failure and volume overload, the company has announced.

The product is indicated for use with a SmartDose On-Body Infuser (West Pharmaceutical Services) single-use subcutaneous administration device, which affixes to the abdomen.

Olivier Le Moal/Getty Images

The infuser is loaded by the patient or caregiver with a prefilled cartridge and is programmed to deliver Furoscix 30 mg over 1 hour followed by a 4-hour infusion at 12.5 mg/h, for a total fixed dose of 80 mg, scPharmaceuticals said in a press release on the drug approval.

Furosemide, a loop diuretic and one of the world’s most frequently used drugs, is conventionally given intravenously in the hospital or orally on an outpatient basis.

The company describes its furosemide preparation, used with the infuser, as “the first and only FDA-approved subcutaneous loop diuretic that delivers [intravenous]-equivalent diuresis at home.” It has been shown to “produce similar diuresis and natriuresis compared to intravenous furosemide.”

“This marks a tremendous opportunity to improve the at-home management of worsening congestion in patients with heart failure who display reduced responsiveness to oral diuretics and require administration of [intravenous] diuretics, which typically requires admission to the hospital,” William T. Abraham, MD, said in the press release.

The FDA approval “is significant and will allow patients to be treated outside of the hospital setting,” said Dr. Abraham, of Ohio State University, Columbus, and an scPharmaceuticals board member.

The Furoscix indication doesn’t cover emergent use or use in acute pulmonary edema, nor is it meant to be used chronically “and should be replaced with oral diuretics as soon as practical,” the company states.

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

A recent medical meeting I attended included multiple sessions on the use of artificial intelligence (AI), a mere preview, I suspect, of what is to come for both patients and physicians.

I vow not to be a contrarian, but I have concerns. If we’d known how cell phones would permeate nearly every waking moment of our lives, would we have built in more protections from the onset?

Although anyone can see the enormous potential of AI in medicine, harnessing the wonders of it without guarding against the dangers could be paramount to texting and driving. 

A palpable disruption in the common work-a-day human interaction is a given. CEOs who mind the bottom line will seek every opportunity to cut personnel whenever machine learning can deliver. As our dependence on algorithms increases, our need to understand electrocardiogram interpretation and echocardiographic calculations will wane. Subtle case information will go undetected. Nuanced subconscious alerts regarding the patient condition will go unnoticed.

These realities are never reflected in the pronouncements of companies who promote and develop AI.
 

The 2-minute echo

In September 2020, Carolyn Lam, MBBS, PhD, and James Hare, MBA, founders of the AI tech company US2.AI, told Healthcare Transformers that AI advances in echocardiology will turn “a manual process of 30 minutes, 250 clicks, with up to 21% variability among fully trained sonographers analyzing the same exam, into an AI-automated process taking 2 minutes, 1 click, with 0% variability.”

Let’s contrast this 2-minute human-machine interaction with the standard 20- to 30-minute human-to-human echocardiography procedure.

Take Mrs. Smith, for instance. She is referred for echocardiography for shortness of breath. She’s shown to a room and instructed to lie down on a table, where she undergoes a brief AI-directed acquisition of images and then a cheery dismissal from the imaging lab. Medical corporate chief financial officers will salivate at the efficiency, the decrease in cost for personnel, and the sharp increase in put-through for the echo lab schedule.

But what if Mrs. Smith gets a standard 30-minute sonographer-directed exam and the astute echocardiographer notes a left ventricular ejection fraction of 38%. A conversation with the patient reveals that she lost her son a few weeks ago. Upon completion of the study, the patient stands up and then adds, “I hope I can sleep in my bed tonight.” Thinking there may be more to the patient’s insomnia than grief-driven anxiety, the sonographer asks her to explain. “I had to sleep in a chair last night because I couldn’t breathe,” Mrs. Smith replies.

The sonographer reasons correctly that Mrs. Smith is likely a few weeks past an acute coronary syndrome for which she didn’t seek attention and is now in heart failure. The consulting cardiologist is alerted. Mrs. Smith is worked into the office schedule a week earlier than planned, and a costly in-patient stay for acute heart failure or worse is avoided.

Here’s a true-life example (some details have been changed to protect the patient’s identity): Mr. Rodriquez was referred for echocardiography because of dizziness. The sonographer notes significant mitral regurgitation and a decline in left ventricular ejection fraction from moderately impaired to severely reduced. When the sonographer inquires about a fresh bruise over Mr. Rodriguez’s left eye, he replies that he “must have fallen, but can’t remember.” The sonographer also notes runs of nonsustained ventricular tachycardia on the echo telemetry, and after a phone call from the echo lab to the ordering physician, Mr. Rodriquez is admitted. Instead of chancing a sudden death at home while awaiting follow-up, he undergoes catheterization and gets an implantable cardioverter defibrillator.

These scenarios illustrate that a 2-minute visit for AI-directed acquisition of echocardiogram images will never garner the protections of a conversation with a human. Any attempts at downplaying the importance of these human interactions are misguided.

Sometimes we embrace the latest advances in medicine while failing to tend to the most rudimentary necessities of data analysis and reporting. Catherine M. Otto, MD, director of the heart valve clinic and a professor of cardiology at the University of Washington Medical Center, Seattle, is a fan of the basics.

At the recent annual congress of the European Society of Cardiology, she commented on the AI-ENHANCED trial, which used an AI decision support algorithm to identify patients with moderate to severe aortic stenosis, which is associated with poor survival if left untreated. She correctly highlighted that while we are discussing the merits of AI-driven assessment of aortic stenosis, we are doing so in an era when many echo interpreters exclude critical information. The vital findings of aortic valve area, Vmax, and ejection fraction are often nowhere to be seen on reports. We should attend to our basic flaws in interpretation and reporting before we shift our focus to AI.
 

Flawed algorithms

Incorrect AI algorithms that are broadly adopted could negatively affect the health of millions.

Perhaps the most unsettling claim is made by causaLens: “Causal AI is the only technology that can reason and make choices like humans do,” the website states. A tantalizing tag line that is categorically untrue.

Our mysterious and complex neurophysiological function of reasoning still eludes understanding, but one thing is certain: medical reasoning originates with listening, seeing, and touching.

As AI infiltrates mainstream medicine, opportunities for hearing, observing, and palpating will be greatly reduced.

Folkert Asselbergs from University Medical Center Utrecht, the Netherlands, who has cautioned against overhyping AI, was the discussant for an ESC study on the use of causal AI to improve  cardiovascular risk estimation.

He flashed a slide of a 2019 Science article on racial bias in an algorithm that U.S. health care systems use.  Remedying that bias “would increase the percentage of Black people receiving additional help from 17.7% to 46.5%,” according to the authors.  

Successful integration of AI-driven technology will come only if we build human interaction into every patient encounter.

I hope I don’t live to see the rise of the physician cyborg.

Artificial intelligence could be the greatest boon since the invention of the stethoscope, but it will be our downfall if we stop administering a healthy dose of humanity to every patient encounter.

Melissa Walton-Shirley, MD, is a clinical cardiologist in Nashville, Tenn., who has retired from full-time invasive cardiology. She disclosed no relevant conflicts of interest.
 

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

A recent medical meeting I attended included multiple sessions on the use of artificial intelligence (AI), a mere preview, I suspect, of what is to come for both patients and physicians.

I vow not to be a contrarian, but I have concerns. If we’d known how cell phones would permeate nearly every waking moment of our lives, would we have built in more protections from the onset?

Although anyone can see the enormous potential of AI in medicine, harnessing the wonders of it without guarding against the dangers could be paramount to texting and driving. 

A palpable disruption in the common work-a-day human interaction is a given. CEOs who mind the bottom line will seek every opportunity to cut personnel whenever machine learning can deliver. As our dependence on algorithms increases, our need to understand electrocardiogram interpretation and echocardiographic calculations will wane. Subtle case information will go undetected. Nuanced subconscious alerts regarding the patient condition will go unnoticed.

These realities are never reflected in the pronouncements of companies who promote and develop AI.
 

The 2-minute echo

In September 2020, Carolyn Lam, MBBS, PhD, and James Hare, MBA, founders of the AI tech company US2.AI, told Healthcare Transformers that AI advances in echocardiology will turn “a manual process of 30 minutes, 250 clicks, with up to 21% variability among fully trained sonographers analyzing the same exam, into an AI-automated process taking 2 minutes, 1 click, with 0% variability.”

Let’s contrast this 2-minute human-machine interaction with the standard 20- to 30-minute human-to-human echocardiography procedure.

Take Mrs. Smith, for instance. She is referred for echocardiography for shortness of breath. She’s shown to a room and instructed to lie down on a table, where she undergoes a brief AI-directed acquisition of images and then a cheery dismissal from the imaging lab. Medical corporate chief financial officers will salivate at the efficiency, the decrease in cost for personnel, and the sharp increase in put-through for the echo lab schedule.

But what if Mrs. Smith gets a standard 30-minute sonographer-directed exam and the astute echocardiographer notes a left ventricular ejection fraction of 38%. A conversation with the patient reveals that she lost her son a few weeks ago. Upon completion of the study, the patient stands up and then adds, “I hope I can sleep in my bed tonight.” Thinking there may be more to the patient’s insomnia than grief-driven anxiety, the sonographer asks her to explain. “I had to sleep in a chair last night because I couldn’t breathe,” Mrs. Smith replies.

The sonographer reasons correctly that Mrs. Smith is likely a few weeks past an acute coronary syndrome for which she didn’t seek attention and is now in heart failure. The consulting cardiologist is alerted. Mrs. Smith is worked into the office schedule a week earlier than planned, and a costly in-patient stay for acute heart failure or worse is avoided.

Here’s a true-life example (some details have been changed to protect the patient’s identity): Mr. Rodriquez was referred for echocardiography because of dizziness. The sonographer notes significant mitral regurgitation and a decline in left ventricular ejection fraction from moderately impaired to severely reduced. When the sonographer inquires about a fresh bruise over Mr. Rodriguez’s left eye, he replies that he “must have fallen, but can’t remember.” The sonographer also notes runs of nonsustained ventricular tachycardia on the echo telemetry, and after a phone call from the echo lab to the ordering physician, Mr. Rodriquez is admitted. Instead of chancing a sudden death at home while awaiting follow-up, he undergoes catheterization and gets an implantable cardioverter defibrillator.

These scenarios illustrate that a 2-minute visit for AI-directed acquisition of echocardiogram images will never garner the protections of a conversation with a human. Any attempts at downplaying the importance of these human interactions are misguided.

Sometimes we embrace the latest advances in medicine while failing to tend to the most rudimentary necessities of data analysis and reporting. Catherine M. Otto, MD, director of the heart valve clinic and a professor of cardiology at the University of Washington Medical Center, Seattle, is a fan of the basics.

At the recent annual congress of the European Society of Cardiology, she commented on the AI-ENHANCED trial, which used an AI decision support algorithm to identify patients with moderate to severe aortic stenosis, which is associated with poor survival if left untreated. She correctly highlighted that while we are discussing the merits of AI-driven assessment of aortic stenosis, we are doing so in an era when many echo interpreters exclude critical information. The vital findings of aortic valve area, Vmax, and ejection fraction are often nowhere to be seen on reports. We should attend to our basic flaws in interpretation and reporting before we shift our focus to AI.
 

Flawed algorithms

Incorrect AI algorithms that are broadly adopted could negatively affect the health of millions.

Perhaps the most unsettling claim is made by causaLens: “Causal AI is the only technology that can reason and make choices like humans do,” the website states. A tantalizing tag line that is categorically untrue.

Our mysterious and complex neurophysiological function of reasoning still eludes understanding, but one thing is certain: medical reasoning originates with listening, seeing, and touching.

As AI infiltrates mainstream medicine, opportunities for hearing, observing, and palpating will be greatly reduced.

Folkert Asselbergs from University Medical Center Utrecht, the Netherlands, who has cautioned against overhyping AI, was the discussant for an ESC study on the use of causal AI to improve  cardiovascular risk estimation.

He flashed a slide of a 2019 Science article on racial bias in an algorithm that U.S. health care systems use.  Remedying that bias “would increase the percentage of Black people receiving additional help from 17.7% to 46.5%,” according to the authors.  

Successful integration of AI-driven technology will come only if we build human interaction into every patient encounter.

I hope I don’t live to see the rise of the physician cyborg.

Artificial intelligence could be the greatest boon since the invention of the stethoscope, but it will be our downfall if we stop administering a healthy dose of humanity to every patient encounter.

Melissa Walton-Shirley, MD, is a clinical cardiologist in Nashville, Tenn., who has retired from full-time invasive cardiology. She disclosed no relevant conflicts of interest.
 

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

A recent medical meeting I attended included multiple sessions on the use of artificial intelligence (AI), a mere preview, I suspect, of what is to come for both patients and physicians.

I vow not to be a contrarian, but I have concerns. If we’d known how cell phones would permeate nearly every waking moment of our lives, would we have built in more protections from the onset?

Although anyone can see the enormous potential of AI in medicine, harnessing the wonders of it without guarding against the dangers could be paramount to texting and driving. 

A palpable disruption in the common work-a-day human interaction is a given. CEOs who mind the bottom line will seek every opportunity to cut personnel whenever machine learning can deliver. As our dependence on algorithms increases, our need to understand electrocardiogram interpretation and echocardiographic calculations will wane. Subtle case information will go undetected. Nuanced subconscious alerts regarding the patient condition will go unnoticed.

These realities are never reflected in the pronouncements of companies who promote and develop AI.
 

The 2-minute echo

In September 2020, Carolyn Lam, MBBS, PhD, and James Hare, MBA, founders of the AI tech company US2.AI, told Healthcare Transformers that AI advances in echocardiology will turn “a manual process of 30 minutes, 250 clicks, with up to 21% variability among fully trained sonographers analyzing the same exam, into an AI-automated process taking 2 minutes, 1 click, with 0% variability.”

Let’s contrast this 2-minute human-machine interaction with the standard 20- to 30-minute human-to-human echocardiography procedure.

Take Mrs. Smith, for instance. She is referred for echocardiography for shortness of breath. She’s shown to a room and instructed to lie down on a table, where she undergoes a brief AI-directed acquisition of images and then a cheery dismissal from the imaging lab. Medical corporate chief financial officers will salivate at the efficiency, the decrease in cost for personnel, and the sharp increase in put-through for the echo lab schedule.

But what if Mrs. Smith gets a standard 30-minute sonographer-directed exam and the astute echocardiographer notes a left ventricular ejection fraction of 38%. A conversation with the patient reveals that she lost her son a few weeks ago. Upon completion of the study, the patient stands up and then adds, “I hope I can sleep in my bed tonight.” Thinking there may be more to the patient’s insomnia than grief-driven anxiety, the sonographer asks her to explain. “I had to sleep in a chair last night because I couldn’t breathe,” Mrs. Smith replies.

The sonographer reasons correctly that Mrs. Smith is likely a few weeks past an acute coronary syndrome for which she didn’t seek attention and is now in heart failure. The consulting cardiologist is alerted. Mrs. Smith is worked into the office schedule a week earlier than planned, and a costly in-patient stay for acute heart failure or worse is avoided.

Here’s a true-life example (some details have been changed to protect the patient’s identity): Mr. Rodriquez was referred for echocardiography because of dizziness. The sonographer notes significant mitral regurgitation and a decline in left ventricular ejection fraction from moderately impaired to severely reduced. When the sonographer inquires about a fresh bruise over Mr. Rodriguez’s left eye, he replies that he “must have fallen, but can’t remember.” The sonographer also notes runs of nonsustained ventricular tachycardia on the echo telemetry, and after a phone call from the echo lab to the ordering physician, Mr. Rodriquez is admitted. Instead of chancing a sudden death at home while awaiting follow-up, he undergoes catheterization and gets an implantable cardioverter defibrillator.

These scenarios illustrate that a 2-minute visit for AI-directed acquisition of echocardiogram images will never garner the protections of a conversation with a human. Any attempts at downplaying the importance of these human interactions are misguided.

Sometimes we embrace the latest advances in medicine while failing to tend to the most rudimentary necessities of data analysis and reporting. Catherine M. Otto, MD, director of the heart valve clinic and a professor of cardiology at the University of Washington Medical Center, Seattle, is a fan of the basics.

At the recent annual congress of the European Society of Cardiology, she commented on the AI-ENHANCED trial, which used an AI decision support algorithm to identify patients with moderate to severe aortic stenosis, which is associated with poor survival if left untreated. She correctly highlighted that while we are discussing the merits of AI-driven assessment of aortic stenosis, we are doing so in an era when many echo interpreters exclude critical information. The vital findings of aortic valve area, Vmax, and ejection fraction are often nowhere to be seen on reports. We should attend to our basic flaws in interpretation and reporting before we shift our focus to AI.
 

Flawed algorithms

Incorrect AI algorithms that are broadly adopted could negatively affect the health of millions.

Perhaps the most unsettling claim is made by causaLens: “Causal AI is the only technology that can reason and make choices like humans do,” the website states. A tantalizing tag line that is categorically untrue.

Our mysterious and complex neurophysiological function of reasoning still eludes understanding, but one thing is certain: medical reasoning originates with listening, seeing, and touching.

As AI infiltrates mainstream medicine, opportunities for hearing, observing, and palpating will be greatly reduced.

Folkert Asselbergs from University Medical Center Utrecht, the Netherlands, who has cautioned against overhyping AI, was the discussant for an ESC study on the use of causal AI to improve  cardiovascular risk estimation.

He flashed a slide of a 2019 Science article on racial bias in an algorithm that U.S. health care systems use.  Remedying that bias “would increase the percentage of Black people receiving additional help from 17.7% to 46.5%,” according to the authors.  

Successful integration of AI-driven technology will come only if we build human interaction into every patient encounter.

I hope I don’t live to see the rise of the physician cyborg.

Artificial intelligence could be the greatest boon since the invention of the stethoscope, but it will be our downfall if we stop administering a healthy dose of humanity to every patient encounter.

Melissa Walton-Shirley, MD, is a clinical cardiologist in Nashville, Tenn., who has retired from full-time invasive cardiology. She disclosed no relevant conflicts of interest.
 

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

Whatever the mechanism of benefit from dapagliflozin (Farxiga) in patients with heart failure (HF) – and potentially also other sodium-glucose cotransporter 2 (SGLT2) inhibitors – its blood pressure lowering effects aren’t likely to contribute much.

Indeed, at least in patients with HF and non-reduced ejection fractions, dapagliflozin has only a modest BP-lowering effect and cuts cardiovascular (CV) risk regardless of baseline pressure or change in systolic BP, suggests a secondary analysis from the large placebo-controlled DELIVER trial.

Systolic BP fell over 1 month by just under 2 mmHg, on average, in trial patients with either mildly reduced or preserved ejection fraction (HFmrEF or HFpEF, respectively) assigned to take dapagliflozin versus placebo.

The effect was achieved without increasing the risk for adverse events from dapagliflozin, even among patients with the lowest baseline systolic pressures. Adverse outcomes overall, however, were more common at the lowest systolic BP level than at higher pressures, researchers reported.

They say the findings should help alleviate long-standing concerns that initiating SGLT2 inhibitors, with their recognized diuretic effects, might present a hazard in patients with HF and low systolic BP.

“It is a consistent theme in heart failure trials that the blood pressure–lowering effect of SGLT2 inhibitors is more modest than it is in non–heart-failure populations,” Senthil Selvaraj, MD, Duke University, Durham, N.C., told this news organization.

Changes to antihypertensive drug therapy throughout the trial, which presumably enhanced BP responses and “might occur more frequently in the placebo group,” Dr. Selvaraj said, “might explain why the blood pressure effect is a little bit more modest in this population.”

Dr. Selvaraj presented the analysis at the Annual Scientific Meeting of the Heart Failure Society of America, held in National Harbor, Md., and is lead author on its same-day publication in JACC: Heart Failure.

The findings “reinforce the clinical benefits of SGLT2 inhibitors in patients with heart failure across the full spectrum of ejection fractions and large range of systolic blood pressures,” said Gregg C. Fonarow, MD, University of California, Los Angeles Medical Center, who was not part of the DELIVER analysis.

The study’s greater adjusted risks for CV and all-cause mortality risks at the lowest baseline systolic pressures “parallels a series of observational analyses from registries, including OPTIMIZE-HF,” Dr. Fonarow observed.

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

Whatever the mechanism of benefit from dapagliflozin (Farxiga) in patients with heart failure (HF) – and potentially also other sodium-glucose cotransporter 2 (SGLT2) inhibitors – its blood pressure lowering effects aren’t likely to contribute much.

Indeed, at least in patients with HF and non-reduced ejection fractions, dapagliflozin has only a modest BP-lowering effect and cuts cardiovascular (CV) risk regardless of baseline pressure or change in systolic BP, suggests a secondary analysis from the large placebo-controlled DELIVER trial.

Systolic BP fell over 1 month by just under 2 mmHg, on average, in trial patients with either mildly reduced or preserved ejection fraction (HFmrEF or HFpEF, respectively) assigned to take dapagliflozin versus placebo.

The effect was achieved without increasing the risk for adverse events from dapagliflozin, even among patients with the lowest baseline systolic pressures. Adverse outcomes overall, however, were more common at the lowest systolic BP level than at higher pressures, researchers reported.

They say the findings should help alleviate long-standing concerns that initiating SGLT2 inhibitors, with their recognized diuretic effects, might present a hazard in patients with HF and low systolic BP.

“It is a consistent theme in heart failure trials that the blood pressure–lowering effect of SGLT2 inhibitors is more modest than it is in non–heart-failure populations,” Senthil Selvaraj, MD, Duke University, Durham, N.C., told this news organization.

Changes to antihypertensive drug therapy throughout the trial, which presumably enhanced BP responses and “might occur more frequently in the placebo group,” Dr. Selvaraj said, “might explain why the blood pressure effect is a little bit more modest in this population.”

Dr. Selvaraj presented the analysis at the Annual Scientific Meeting of the Heart Failure Society of America, held in National Harbor, Md., and is lead author on its same-day publication in JACC: Heart Failure.

The findings “reinforce the clinical benefits of SGLT2 inhibitors in patients with heart failure across the full spectrum of ejection fractions and large range of systolic blood pressures,” said Gregg C. Fonarow, MD, University of California, Los Angeles Medical Center, who was not part of the DELIVER analysis.

The study’s greater adjusted risks for CV and all-cause mortality risks at the lowest baseline systolic pressures “parallels a series of observational analyses from registries, including OPTIMIZE-HF,” Dr. Fonarow observed.

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

Whatever the mechanism of benefit from dapagliflozin (Farxiga) in patients with heart failure (HF) – and potentially also other sodium-glucose cotransporter 2 (SGLT2) inhibitors – its blood pressure lowering effects aren’t likely to contribute much.

Indeed, at least in patients with HF and non-reduced ejection fractions, dapagliflozin has only a modest BP-lowering effect and cuts cardiovascular (CV) risk regardless of baseline pressure or change in systolic BP, suggests a secondary analysis from the large placebo-controlled DELIVER trial.

Systolic BP fell over 1 month by just under 2 mmHg, on average, in trial patients with either mildly reduced or preserved ejection fraction (HFmrEF or HFpEF, respectively) assigned to take dapagliflozin versus placebo.

The effect was achieved without increasing the risk for adverse events from dapagliflozin, even among patients with the lowest baseline systolic pressures. Adverse outcomes overall, however, were more common at the lowest systolic BP level than at higher pressures, researchers reported.

They say the findings should help alleviate long-standing concerns that initiating SGLT2 inhibitors, with their recognized diuretic effects, might present a hazard in patients with HF and low systolic BP.

“It is a consistent theme in heart failure trials that the blood pressure–lowering effect of SGLT2 inhibitors is more modest than it is in non–heart-failure populations,” Senthil Selvaraj, MD, Duke University, Durham, N.C., told this news organization.

Changes to antihypertensive drug therapy throughout the trial, which presumably enhanced BP responses and “might occur more frequently in the placebo group,” Dr. Selvaraj said, “might explain why the blood pressure effect is a little bit more modest in this population.”

Dr. Selvaraj presented the analysis at the Annual Scientific Meeting of the Heart Failure Society of America, held in National Harbor, Md., and is lead author on its same-day publication in JACC: Heart Failure.

The findings “reinforce the clinical benefits of SGLT2 inhibitors in patients with heart failure across the full spectrum of ejection fractions and large range of systolic blood pressures,” said Gregg C. Fonarow, MD, University of California, Los Angeles Medical Center, who was not part of the DELIVER analysis.

The study’s greater adjusted risks for CV and all-cause mortality risks at the lowest baseline systolic pressures “parallels a series of observational analyses from registries, including OPTIMIZE-HF,” Dr. Fonarow observed.

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

Weight loss after bariatric surgery was linked with visceral fat reduction as well as reduced blood pressure, fasting glucose, and left ventricular remodeling, based an imaging study in 213 patients.

“We found that ventricular function measured by strain imaging improved in both the left and right sides of the heart, but function measured in the traditional method using endocardial motion [in other words, ejection fraction] actually worsened,” senior investigator Barry A. Borlaug, MD, said in an interview.

Although previous studies have shown positive effects of weight loss on the heart after bariatric surgery, most have been short term and have not specifically examined the effects of visceral fat reduction, wrote the investigators.

“We are in the middle of an increasing epidemic of obesity worldwide, but particularly in the United States, where it is currently projected that one in two adults will be obese by 2030,” added Dr. Borlaug of Mayo Clinic, Rochester, Minn. “Heart failure with preserved ejection fraction (HFpEF) is growing in tandem, and numerous recent studies have shown that obesity is one of the strongest risk factors for developing HFpEF, and that the severity of HFpEF is intimately linked to excess body fat. This suggests that therapies to reduce body fat could improve the cardiac abnormalities that cause HFpEF, which was our focus in this study,” he explained.

In the study, published in the Journal of the American College of Cardiology, the researchers reviewed echocardiography data from 213 obese patients before and more than 180 days after bariatric surgery. They also measured abdominal visceral adipose tissue (VAT) of 52 patients via computed tomography. The average age of the patients was 54 years, the average body mass index was 45 kg/m², and 67% were women. Comorbidities included hypertension, diabetes, dyslipidemia, and obstructive sleep apnea.

The primary outcome was changes in cardiac structure and function.

After a median follow-up of 5.3 years, patients overall averaged a 23% reduction in body weight and a 22% reduction in BMI. In the 52 patients with abdominal scans, the VAT area decreased by 30% overall. Changes in left ventricular mass were significantly correlated to changes in the VAT.

Epicardial adipose thickness decreased by 14% overall. Left and right ventricular longitudinal strains improved at follow-up, but left atrial strain deteriorated, the researchers noted.

Although the mechanism of action remains unclear, the results suggest that left ventricular remodeling was associated with visceral adiposity rather than subcutaneous fat, the researchers wrote.

They also found that right ventricular strain was negatively correlated with VAT, but not with body weight or BMI.

“These findings suggest that weight loss, particularly reduction in visceral adiposity, benefits [right ventricular] structure and function in a manner akin to that observed in the [left ventricle],” the researchers noted.

Some surprises and limitations

Dr. Borlaug said he found some, but not all, of the results surprising. “Earlier studies had shown evidence for benefit from weight loss on cardiac structure and function, but had been limited by smaller sample sizes, shorter durations of evaluation, and variable methods used,” he said in an interview.

The findings that strain imaging showed both left and right ventricular function improved while EF declined “shows some of the problems with using EF, as it is affected by chamber size and geometry. We have previously shown that patients with HFpEF display an increase in fat around the heart, and this affects cardiac function and interaction between the left and right sides of the heart, so we expected to see that this fat depot would be reduced, and this was indeed the case,” Dr. Borlaug added.

In the current study, “visceral fat was most strongly tied to the heart remodeling in obesity, and changes in visceral fat were most strongly tied to improvements in cardiac structure following weight loss,” Dr. Borlaug told this news organization. “This further supports this concept that excess visceral fat plays a key role in HFpEF, especially in the abdomen and around the heart,” he said.

However, “The biggest surprise was the discordant effects in the left atrium,” Dr. Borlaug said. “Left atrial remodeling and dysfunction play a crucial role in HFpEF as well, and we expected that this would improve following weight loss, but in fact we observed that left atrial function deteriorated, and other indicators of atrial myopathy worsened, including higher estimates of left atrial pressures and increased prevalence of atrial fibrillation,” he said.

This difference emphasizes that weight loss may not address all abnormalities that lead to HFpEF, although a key limitation of the current study was the lack of a control group of patients with the same degree of obesity and no weight-loss intervention, and the deterioration in left atrial function might have been even greater in the absence of weight loss, Dr. Borlaug added.
 

Larger numbers support effects

Previous research shows that structural heart changes associated with obesity can be reversed through weight loss, but the current study fills a gap by providing long-term data in a larger sample than previously studied, wrote Paul Heidenreich, MD, of Stanford (Calif.) University in an accompanying editorial).

“There has been uncertainty regarding the prolonged effect of weight loss on cardiac function; this study was larger than many prior studies and provided a longer follow-up,” Dr. Heidenreich said in an interview.

“One unusual finding was that, while weight loss led to left ventricle reverse remodeling (reduction in wall thickness), the same effect was not seen for the left atrium; the left atrial size continued to increase,” he said. “I would have expected the left atrial changes to mirror the changes in the left ventricle,” he noted.

The findings support the greater cardiac risk of visceral vs. subcutaneous adipose tissue, and although body mass index will retain prognostic value, measures of central obesity are more likely predictors of cardiac structural changes and events and should be reported in clinical studies, Dr. Heidenreich wrote.

However, “We need a better understanding of the factors that influence left atrial remodeling and reverse remodeling,” Dr. Heidenreich told this news organization. “While left ventricular compliance and pressure play a role, there are other factors that need to be elucidated,” he said.

 

Studies in progress may inform practice

The current data call for further study to test novel treatments to facilitate weight loss in patients with HFpEF and those at risk for HFpEF, and some of these studies with medicines are underway, Dr. Borlaug said in the interview.

“Until such studies are completed, we will not truly understand the effects of weight loss on the heart, but the present data certainly provide strong support that patients who have obesity and HFpEF or are at risk for HFpEF should try to lose weight through lifestyle interventions,” he said. 

Whether the cardiac changes seen in the current study would be different with nonsurgical weight loss remains a key question because many obese patients are reluctant to undergo bariatric surgery, Dr. Borlaug said. “We cannot assess whether the effects would differ with nonsurgical weight loss, and this requires further study,” he added.

As for additional research, “Randomized, controlled trials of weight-loss interventions, with appropriate controls and comprehensive assessments of cardiac structure, function, and hemodynamics will be most informative,” said Dr. Borlaug. “Larger trials powered to evaluate cardiovascular outcomes such as heart failure hospitalization or cardiovascular death also are critically important to better understand the role of weight loss to treat and prevent HFpEF, the ultimate form of obesity-related heart disease,” he emphasized.

The study was supported in part by grants to lead author Dr. Hidemi Sorimachi of the Mayo Clinic from the Uehara Memorial Foundation, Japan, and to corresponding author Dr. Borlaug from the National Institutes of Health. Dr. Borlaug also disclosed previous grants from National Institutes of Health/National Heart, Lung, and Blood Institute, AstraZeneca, Corvia, Medtronic, GlaxoSmithKline, Mesoblast, Novartis, and Tenax Therapeutics; and consulting fees from Actelion, Amgen, Aria, Axon Therapies, Boehringer Ingelheim, Edwards Lifesciences, Eli Lilly, Imbria, Janssen, Merck, Novo Nordisk, and VADovations. Dr. Heidenreich had no financial disclosures.

Weight loss after bariatric surgery was linked with visceral fat reduction as well as reduced blood pressure, fasting glucose, and left ventricular remodeling, based an imaging study in 213 patients.

“We found that ventricular function measured by strain imaging improved in both the left and right sides of the heart, but function measured in the traditional method using endocardial motion [in other words, ejection fraction] actually worsened,” senior investigator Barry A. Borlaug, MD, said in an interview.

Although previous studies have shown positive effects of weight loss on the heart after bariatric surgery, most have been short term and have not specifically examined the effects of visceral fat reduction, wrote the investigators.

“We are in the middle of an increasing epidemic of obesity worldwide, but particularly in the United States, where it is currently projected that one in two adults will be obese by 2030,” added Dr. Borlaug of Mayo Clinic, Rochester, Minn. “Heart failure with preserved ejection fraction (HFpEF) is growing in tandem, and numerous recent studies have shown that obesity is one of the strongest risk factors for developing HFpEF, and that the severity of HFpEF is intimately linked to excess body fat. This suggests that therapies to reduce body fat could improve the cardiac abnormalities that cause HFpEF, which was our focus in this study,” he explained.

In the study, published in the Journal of the American College of Cardiology, the researchers reviewed echocardiography data from 213 obese patients before and more than 180 days after bariatric surgery. They also measured abdominal visceral adipose tissue (VAT) of 52 patients via computed tomography. The average age of the patients was 54 years, the average body mass index was 45 kg/m², and 67% were women. Comorbidities included hypertension, diabetes, dyslipidemia, and obstructive sleep apnea.

The primary outcome was changes in cardiac structure and function.

After a median follow-up of 5.3 years, patients overall averaged a 23% reduction in body weight and a 22% reduction in BMI. In the 52 patients with abdominal scans, the VAT area decreased by 30% overall. Changes in left ventricular mass were significantly correlated to changes in the VAT.

Epicardial adipose thickness decreased by 14% overall. Left and right ventricular longitudinal strains improved at follow-up, but left atrial strain deteriorated, the researchers noted.

Although the mechanism of action remains unclear, the results suggest that left ventricular remodeling was associated with visceral adiposity rather than subcutaneous fat, the researchers wrote.

They also found that right ventricular strain was negatively correlated with VAT, but not with body weight or BMI.

“These findings suggest that weight loss, particularly reduction in visceral adiposity, benefits [right ventricular] structure and function in a manner akin to that observed in the [left ventricle],” the researchers noted.

Some surprises and limitations

Dr. Borlaug said he found some, but not all, of the results surprising. “Earlier studies had shown evidence for benefit from weight loss on cardiac structure and function, but had been limited by smaller sample sizes, shorter durations of evaluation, and variable methods used,” he said in an interview.

The findings that strain imaging showed both left and right ventricular function improved while EF declined “shows some of the problems with using EF, as it is affected by chamber size and geometry. We have previously shown that patients with HFpEF display an increase in fat around the heart, and this affects cardiac function and interaction between the left and right sides of the heart, so we expected to see that this fat depot would be reduced, and this was indeed the case,” Dr. Borlaug added.

In the current study, “visceral fat was most strongly tied to the heart remodeling in obesity, and changes in visceral fat were most strongly tied to improvements in cardiac structure following weight loss,” Dr. Borlaug told this news organization. “This further supports this concept that excess visceral fat plays a key role in HFpEF, especially in the abdomen and around the heart,” he said.

However, “The biggest surprise was the discordant effects in the left atrium,” Dr. Borlaug said. “Left atrial remodeling and dysfunction play a crucial role in HFpEF as well, and we expected that this would improve following weight loss, but in fact we observed that left atrial function deteriorated, and other indicators of atrial myopathy worsened, including higher estimates of left atrial pressures and increased prevalence of atrial fibrillation,” he said.

This difference emphasizes that weight loss may not address all abnormalities that lead to HFpEF, although a key limitation of the current study was the lack of a control group of patients with the same degree of obesity and no weight-loss intervention, and the deterioration in left atrial function might have been even greater in the absence of weight loss, Dr. Borlaug added.
 

Larger numbers support effects

Previous research shows that structural heart changes associated with obesity can be reversed through weight loss, but the current study fills a gap by providing long-term data in a larger sample than previously studied, wrote Paul Heidenreich, MD, of Stanford (Calif.) University in an accompanying editorial).

“There has been uncertainty regarding the prolonged effect of weight loss on cardiac function; this study was larger than many prior studies and provided a longer follow-up,” Dr. Heidenreich said in an interview.

“One unusual finding was that, while weight loss led to left ventricle reverse remodeling (reduction in wall thickness), the same effect was not seen for the left atrium; the left atrial size continued to increase,” he said. “I would have expected the left atrial changes to mirror the changes in the left ventricle,” he noted.

The findings support the greater cardiac risk of visceral vs. subcutaneous adipose tissue, and although body mass index will retain prognostic value, measures of central obesity are more likely predictors of cardiac structural changes and events and should be reported in clinical studies, Dr. Heidenreich wrote.

However, “We need a better understanding of the factors that influence left atrial remodeling and reverse remodeling,” Dr. Heidenreich told this news organization. “While left ventricular compliance and pressure play a role, there are other factors that need to be elucidated,” he said.

 

Studies in progress may inform practice

The current data call for further study to test novel treatments to facilitate weight loss in patients with HFpEF and those at risk for HFpEF, and some of these studies with medicines are underway, Dr. Borlaug said in the interview.

“Until such studies are completed, we will not truly understand the effects of weight loss on the heart, but the present data certainly provide strong support that patients who have obesity and HFpEF or are at risk for HFpEF should try to lose weight through lifestyle interventions,” he said. 

Whether the cardiac changes seen in the current study would be different with nonsurgical weight loss remains a key question because many obese patients are reluctant to undergo bariatric surgery, Dr. Borlaug said. “We cannot assess whether the effects would differ with nonsurgical weight loss, and this requires further study,” he added.

As for additional research, “Randomized, controlled trials of weight-loss interventions, with appropriate controls and comprehensive assessments of cardiac structure, function, and hemodynamics will be most informative,” said Dr. Borlaug. “Larger trials powered to evaluate cardiovascular outcomes such as heart failure hospitalization or cardiovascular death also are critically important to better understand the role of weight loss to treat and prevent HFpEF, the ultimate form of obesity-related heart disease,” he emphasized.

The study was supported in part by grants to lead author Dr. Hidemi Sorimachi of the Mayo Clinic from the Uehara Memorial Foundation, Japan, and to corresponding author Dr. Borlaug from the National Institutes of Health. Dr. Borlaug also disclosed previous grants from National Institutes of Health/National Heart, Lung, and Blood Institute, AstraZeneca, Corvia, Medtronic, GlaxoSmithKline, Mesoblast, Novartis, and Tenax Therapeutics; and consulting fees from Actelion, Amgen, Aria, Axon Therapies, Boehringer Ingelheim, Edwards Lifesciences, Eli Lilly, Imbria, Janssen, Merck, Novo Nordisk, and VADovations. Dr. Heidenreich had no financial disclosures.

Weight loss after bariatric surgery was linked with visceral fat reduction as well as reduced blood pressure, fasting glucose, and left ventricular remodeling, based an imaging study in 213 patients.

“We found that ventricular function measured by strain imaging improved in both the left and right sides of the heart, but function measured in the traditional method using endocardial motion [in other words, ejection fraction] actually worsened,” senior investigator Barry A. Borlaug, MD, said in an interview.

Although previous studies have shown positive effects of weight loss on the heart after bariatric surgery, most have been short term and have not specifically examined the effects of visceral fat reduction, wrote the investigators.

“We are in the middle of an increasing epidemic of obesity worldwide, but particularly in the United States, where it is currently projected that one in two adults will be obese by 2030,” added Dr. Borlaug of Mayo Clinic, Rochester, Minn. “Heart failure with preserved ejection fraction (HFpEF) is growing in tandem, and numerous recent studies have shown that obesity is one of the strongest risk factors for developing HFpEF, and that the severity of HFpEF is intimately linked to excess body fat. This suggests that therapies to reduce body fat could improve the cardiac abnormalities that cause HFpEF, which was our focus in this study,” he explained.

In the study, published in the Journal of the American College of Cardiology, the researchers reviewed echocardiography data from 213 obese patients before and more than 180 days after bariatric surgery. They also measured abdominal visceral adipose tissue (VAT) of 52 patients via computed tomography. The average age of the patients was 54 years, the average body mass index was 45 kg/m², and 67% were women. Comorbidities included hypertension, diabetes, dyslipidemia, and obstructive sleep apnea.

The primary outcome was changes in cardiac structure and function.

After a median follow-up of 5.3 years, patients overall averaged a 23% reduction in body weight and a 22% reduction in BMI. In the 52 patients with abdominal scans, the VAT area decreased by 30% overall. Changes in left ventricular mass were significantly correlated to changes in the VAT.

Epicardial adipose thickness decreased by 14% overall. Left and right ventricular longitudinal strains improved at follow-up, but left atrial strain deteriorated, the researchers noted.

Although the mechanism of action remains unclear, the results suggest that left ventricular remodeling was associated with visceral adiposity rather than subcutaneous fat, the researchers wrote.

They also found that right ventricular strain was negatively correlated with VAT, but not with body weight or BMI.

“These findings suggest that weight loss, particularly reduction in visceral adiposity, benefits [right ventricular] structure and function in a manner akin to that observed in the [left ventricle],” the researchers noted.

Some surprises and limitations

Dr. Borlaug said he found some, but not all, of the results surprising. “Earlier studies had shown evidence for benefit from weight loss on cardiac structure and function, but had been limited by smaller sample sizes, shorter durations of evaluation, and variable methods used,” he said in an interview.

The findings that strain imaging showed both left and right ventricular function improved while EF declined “shows some of the problems with using EF, as it is affected by chamber size and geometry. We have previously shown that patients with HFpEF display an increase in fat around the heart, and this affects cardiac function and interaction between the left and right sides of the heart, so we expected to see that this fat depot would be reduced, and this was indeed the case,” Dr. Borlaug added.

In the current study, “visceral fat was most strongly tied to the heart remodeling in obesity, and changes in visceral fat were most strongly tied to improvements in cardiac structure following weight loss,” Dr. Borlaug told this news organization. “This further supports this concept that excess visceral fat plays a key role in HFpEF, especially in the abdomen and around the heart,” he said.

However, “The biggest surprise was the discordant effects in the left atrium,” Dr. Borlaug said. “Left atrial remodeling and dysfunction play a crucial role in HFpEF as well, and we expected that this would improve following weight loss, but in fact we observed that left atrial function deteriorated, and other indicators of atrial myopathy worsened, including higher estimates of left atrial pressures and increased prevalence of atrial fibrillation,” he said.

This difference emphasizes that weight loss may not address all abnormalities that lead to HFpEF, although a key limitation of the current study was the lack of a control group of patients with the same degree of obesity and no weight-loss intervention, and the deterioration in left atrial function might have been even greater in the absence of weight loss, Dr. Borlaug added.
 

Larger numbers support effects

Previous research shows that structural heart changes associated with obesity can be reversed through weight loss, but the current study fills a gap by providing long-term data in a larger sample than previously studied, wrote Paul Heidenreich, MD, of Stanford (Calif.) University in an accompanying editorial).

“There has been uncertainty regarding the prolonged effect of weight loss on cardiac function; this study was larger than many prior studies and provided a longer follow-up,” Dr. Heidenreich said in an interview.

“One unusual finding was that, while weight loss led to left ventricle reverse remodeling (reduction in wall thickness), the same effect was not seen for the left atrium; the left atrial size continued to increase,” he said. “I would have expected the left atrial changes to mirror the changes in the left ventricle,” he noted.

The findings support the greater cardiac risk of visceral vs. subcutaneous adipose tissue, and although body mass index will retain prognostic value, measures of central obesity are more likely predictors of cardiac structural changes and events and should be reported in clinical studies, Dr. Heidenreich wrote.

However, “We need a better understanding of the factors that influence left atrial remodeling and reverse remodeling,” Dr. Heidenreich told this news organization. “While left ventricular compliance and pressure play a role, there are other factors that need to be elucidated,” he said.

 

Studies in progress may inform practice

The current data call for further study to test novel treatments to facilitate weight loss in patients with HFpEF and those at risk for HFpEF, and some of these studies with medicines are underway, Dr. Borlaug said in the interview.

“Until such studies are completed, we will not truly understand the effects of weight loss on the heart, but the present data certainly provide strong support that patients who have obesity and HFpEF or are at risk for HFpEF should try to lose weight through lifestyle interventions,” he said. 

Whether the cardiac changes seen in the current study would be different with nonsurgical weight loss remains a key question because many obese patients are reluctant to undergo bariatric surgery, Dr. Borlaug said. “We cannot assess whether the effects would differ with nonsurgical weight loss, and this requires further study,” he added.

As for additional research, “Randomized, controlled trials of weight-loss interventions, with appropriate controls and comprehensive assessments of cardiac structure, function, and hemodynamics will be most informative,” said Dr. Borlaug. “Larger trials powered to evaluate cardiovascular outcomes such as heart failure hospitalization or cardiovascular death also are critically important to better understand the role of weight loss to treat and prevent HFpEF, the ultimate form of obesity-related heart disease,” he emphasized.

The study was supported in part by grants to lead author Dr. Hidemi Sorimachi of the Mayo Clinic from the Uehara Memorial Foundation, Japan, and to corresponding author Dr. Borlaug from the National Institutes of Health. Dr. Borlaug also disclosed previous grants from National Institutes of Health/National Heart, Lung, and Blood Institute, AstraZeneca, Corvia, Medtronic, GlaxoSmithKline, Mesoblast, Novartis, and Tenax Therapeutics; and consulting fees from Actelion, Amgen, Aria, Axon Therapies, Boehringer Ingelheim, Edwards Lifesciences, Eli Lilly, Imbria, Janssen, Merck, Novo Nordisk, and VADovations. Dr. Heidenreich had no financial disclosures.

Restriction of dietary salt to alleviate or prevent volume overload in patients with acute decompensated heart failure (ADHF) is common hospital practice, but without a solid evidence base. A trial testing whether taking salt pills might have benefits for patients with ADHF undergoing intensive diuresis, therefore, may seem a bit counterintuitive.

In just such a randomized, placebo-controlled trial, the approach made no difference to weight loss on diuresis, a proxy for volume reduction, or to serum creatinine levels in ADHF patients receiving high-dose intravenous diuretic therapy.

Georges Lievre / Fotolia.com

The patients consumed the extra salt during their intravenous therapy in the form of tablets providing 6 g sodium chloride daily on top of their hospital-provided, low-sodium meals.

During that time, serum sodium levels remained stable for the 34 patients assigned to the salt tablets but dropped significantly in the 31 given placebo pills.

They lost about the same weight, averages of 4 kg and 4.6 kg (8.8-10 lb), respectively, and their urine output was also similar. Patients who took the salt tablets showed less of an increase in blood urea nitrogen (BUN) at both 96 hours and at discharge.

The findings “challenge the routine practice of sodium chloride restriction in acute heart failure, something done thousands of times a day, millions of times a year,” Robert A. Montgomery, MD, Cleveland Clinic, said when presenting the study at the annual scientific meeting of the Heart Failure Society of America.

The trial, called OSPREY-AHF (Oral Sodium to Preserve Renal Efficiency in Acute Heart Failure), also may encourage a shift in ADHF management from a preoccupation with salt restriction to focus more on fighting fluid retention.

OSPREY-HF took on “an established practice that doesn’t have much high-quality evidentiary support,” one guided primarily by consensus and observational data, Montgomery said in an interview.

There are also potential downsides to dietary sodium restriction, including some that may complicate or block ADHF therapies.

“Low-sodium diets can be associated with decreased caloric intake and nutritional quality,” Dr. Montgomery observed. And observational studies suggest that “patients who are on a low sodium diet can develop increased neurohormonal activation. The kidney is not sensing salt, and so starts ramping up the hormones,” which promotes diuretic resistance.

But emerging evidence also suggests “that giving sodium chloride in the form of hypertonic saline can help patients who are diuretic resistant.” The intervention, which appears to attenuate the neurohormonal activation associated with high-dose intravenous diuretics, Dr. Montgomery noted, helped inspire the design of OSPREY-AHF.

Edema consists of “a gallon of water and a pinch of salt, so we really should stop being so salt-centric and think much more about water as the problem in decompensated heart failure,” said John G.F. Cleland, MD, PhD, during the question-and-answer period after Montgomery’s presentation. Dr. Cleland, of the University of Glasgow Institute of Health and Wellbeing, is not connected to OSPREY-AHF.

“I think that maybe we overinterpret how important salt is” as a focus of volume management in ADHF, offered David Lanfear, MD, Henry Ford Health System, Detroit, who is also not part of the study.

OSPREY-AHF was well conducted but applies to a “very specific” clinical setting, Dr. Lanfear said in an interview. “These people are getting aggressive diuresis, a big dose and continuous infusion. It’s not everybody that has heart failure.”

Although the study was small, “I think it will fuel interest in this area and, probably, further investigation,” he said. The trial on its own won’t change practice, “but it will raise some eyebrows.”

The trial included patients with ADHF who have been “admitted to a cardiovascular medicine floor, not the intensive care unit” and were receiving at least 10 mg per hour of furosemide. It excluded any who were “hypernatremic or severely hyponatremic,” said Dr. Montgomery when presenting the study. They were required to have an initial estimated glomerular filtration rate (eGFR) of at least 15 mL/min per 1.73 m².

The patients were randomly assigned double blind at a single center to receive tablets providing 2 g sodium chloride or placebo pills – 34 and 31 patients, respectively – three times daily during intravenous diuresis.

At 96 hours, the two groups showed no difference in change in creatinine levels or change in weight, both primary endpoints. Nor did they differ in urine output or change in eGFR. But serum sodium levels fell further, and BUN levels went up more in those given placebo.

The two groups showed no differences in hospital length of stay, use of renal replacement therapy at 90 days, ICU time during the index hospitalization, 30-day readmission, or 90-day mortality – although the trial wasn’t powered for clinical outcomes, Dr. Montgomery reported.

"We have patients who complain about their sodium-restricted diet, we have patients that have cachexia, who have a lot of complaints about provider-ordered meals and recommendations,” Dr. Montgomery explained in an interview.

Clinicians provide education and invest a lot of effort into getting patients with heart failure to start and maintain a low-sodium diet, he said. “But a low-sodium diet, in prior studies – and our study adds to this – is not a lever that actually seems to positively or adversely affect patients.”

Dr. Montgomery pointed to the recently published SODIUM-HF trial comparing low-sodium and unrestricted-sodium diets in outpatients with heart failure. It saw no clinical benefit from the low-sodium intervention.

Until studies show, potentially, that sodium restriction in hospitalized patients with heart failure makes a clinical difference, Dr. Montgomery said, “I’d say we should invest our time in things that we know are the most helpful, like getting them on guideline-directed medical therapy, when instead we spend an enormous amount of time counseling on and enforcing dietary restriction.”

Support for this study was provided by Cleveland Clinic Heart Vascular and Thoracic Institute’s Wilson Grant and Kaufman Center for Heart Failure Treatment and Recovery Grant. Dr. Lanfear disclosed research support from SomaLogic and Lilly; consulting for Abbott Laboratories, AstraZeneca, Janssen, Martin Pharmaceuticals, and Amgen; and serving on advisory panels for Illumina and Cytokinetics. Dr. Montgomery and Dr. Cleland disclosed no relevant financial relationships.

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

Restriction of dietary salt to alleviate or prevent volume overload in patients with acute decompensated heart failure (ADHF) is common hospital practice, but without a solid evidence base. A trial testing whether taking salt pills might have benefits for patients with ADHF undergoing intensive diuresis, therefore, may seem a bit counterintuitive.

In just such a randomized, placebo-controlled trial, the approach made no difference to weight loss on diuresis, a proxy for volume reduction, or to serum creatinine levels in ADHF patients receiving high-dose intravenous diuretic therapy.

Georges Lievre / Fotolia.com

The patients consumed the extra salt during their intravenous therapy in the form of tablets providing 6 g sodium chloride daily on top of their hospital-provided, low-sodium meals.

During that time, serum sodium levels remained stable for the 34 patients assigned to the salt tablets but dropped significantly in the 31 given placebo pills.

They lost about the same weight, averages of 4 kg and 4.6 kg (8.8-10 lb), respectively, and their urine output was also similar. Patients who took the salt tablets showed less of an increase in blood urea nitrogen (BUN) at both 96 hours and at discharge.

The findings “challenge the routine practice of sodium chloride restriction in acute heart failure, something done thousands of times a day, millions of times a year,” Robert A. Montgomery, MD, Cleveland Clinic, said when presenting the study at the annual scientific meeting of the Heart Failure Society of America.

The trial, called OSPREY-AHF (Oral Sodium to Preserve Renal Efficiency in Acute Heart Failure), also may encourage a shift in ADHF management from a preoccupation with salt restriction to focus more on fighting fluid retention.

OSPREY-HF took on “an established practice that doesn’t have much high-quality evidentiary support,” one guided primarily by consensus and observational data, Montgomery said in an interview.

There are also potential downsides to dietary sodium restriction, including some that may complicate or block ADHF therapies.

“Low-sodium diets can be associated with decreased caloric intake and nutritional quality,” Dr. Montgomery observed. And observational studies suggest that “patients who are on a low sodium diet can develop increased neurohormonal activation. The kidney is not sensing salt, and so starts ramping up the hormones,” which promotes diuretic resistance.

But emerging evidence also suggests “that giving sodium chloride in the form of hypertonic saline can help patients who are diuretic resistant.” The intervention, which appears to attenuate the neurohormonal activation associated with high-dose intravenous diuretics, Dr. Montgomery noted, helped inspire the design of OSPREY-AHF.

Edema consists of “a gallon of water and a pinch of salt, so we really should stop being so salt-centric and think much more about water as the problem in decompensated heart failure,” said John G.F. Cleland, MD, PhD, during the question-and-answer period after Montgomery’s presentation. Dr. Cleland, of the University of Glasgow Institute of Health and Wellbeing, is not connected to OSPREY-AHF.

“I think that maybe we overinterpret how important salt is” as a focus of volume management in ADHF, offered David Lanfear, MD, Henry Ford Health System, Detroit, who is also not part of the study.

OSPREY-AHF was well conducted but applies to a “very specific” clinical setting, Dr. Lanfear said in an interview. “These people are getting aggressive diuresis, a big dose and continuous infusion. It’s not everybody that has heart failure.”

Although the study was small, “I think it will fuel interest in this area and, probably, further investigation,” he said. The trial on its own won’t change practice, “but it will raise some eyebrows.”

The trial included patients with ADHF who have been “admitted to a cardiovascular medicine floor, not the intensive care unit” and were receiving at least 10 mg per hour of furosemide. It excluded any who were “hypernatremic or severely hyponatremic,” said Dr. Montgomery when presenting the study. They were required to have an initial estimated glomerular filtration rate (eGFR) of at least 15 mL/min per 1.73 m².

The patients were randomly assigned double blind at a single center to receive tablets providing 2 g sodium chloride or placebo pills – 34 and 31 patients, respectively – three times daily during intravenous diuresis.

At 96 hours, the two groups showed no difference in change in creatinine levels or change in weight, both primary endpoints. Nor did they differ in urine output or change in eGFR. But serum sodium levels fell further, and BUN levels went up more in those given placebo.

The two groups showed no differences in hospital length of stay, use of renal replacement therapy at 90 days, ICU time during the index hospitalization, 30-day readmission, or 90-day mortality – although the trial wasn’t powered for clinical outcomes, Dr. Montgomery reported.

"We have patients who complain about their sodium-restricted diet, we have patients that have cachexia, who have a lot of complaints about provider-ordered meals and recommendations,” Dr. Montgomery explained in an interview.

Clinicians provide education and invest a lot of effort into getting patients with heart failure to start and maintain a low-sodium diet, he said. “But a low-sodium diet, in prior studies – and our study adds to this – is not a lever that actually seems to positively or adversely affect patients.”

Dr. Montgomery pointed to the recently published SODIUM-HF trial comparing low-sodium and unrestricted-sodium diets in outpatients with heart failure. It saw no clinical benefit from the low-sodium intervention.

Until studies show, potentially, that sodium restriction in hospitalized patients with heart failure makes a clinical difference, Dr. Montgomery said, “I’d say we should invest our time in things that we know are the most helpful, like getting them on guideline-directed medical therapy, when instead we spend an enormous amount of time counseling on and enforcing dietary restriction.”

Support for this study was provided by Cleveland Clinic Heart Vascular and Thoracic Institute’s Wilson Grant and Kaufman Center for Heart Failure Treatment and Recovery Grant. Dr. Lanfear disclosed research support from SomaLogic and Lilly; consulting for Abbott Laboratories, AstraZeneca, Janssen, Martin Pharmaceuticals, and Amgen; and serving on advisory panels for Illumina and Cytokinetics. Dr. Montgomery and Dr. Cleland disclosed no relevant financial relationships.

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

Restriction of dietary salt to alleviate or prevent volume overload in patients with acute decompensated heart failure (ADHF) is common hospital practice, but without a solid evidence base. A trial testing whether taking salt pills might have benefits for patients with ADHF undergoing intensive diuresis, therefore, may seem a bit counterintuitive.

In just such a randomized, placebo-controlled trial, the approach made no difference to weight loss on diuresis, a proxy for volume reduction, or to serum creatinine levels in ADHF patients receiving high-dose intravenous diuretic therapy.

Georges Lievre / Fotolia.com

The patients consumed the extra salt during their intravenous therapy in the form of tablets providing 6 g sodium chloride daily on top of their hospital-provided, low-sodium meals.

During that time, serum sodium levels remained stable for the 34 patients assigned to the salt tablets but dropped significantly in the 31 given placebo pills.

They lost about the same weight, averages of 4 kg and 4.6 kg (8.8-10 lb), respectively, and their urine output was also similar. Patients who took the salt tablets showed less of an increase in blood urea nitrogen (BUN) at both 96 hours and at discharge.

The findings “challenge the routine practice of sodium chloride restriction in acute heart failure, something done thousands of times a day, millions of times a year,” Robert A. Montgomery, MD, Cleveland Clinic, said when presenting the study at the annual scientific meeting of the Heart Failure Society of America.

The trial, called OSPREY-AHF (Oral Sodium to Preserve Renal Efficiency in Acute Heart Failure), also may encourage a shift in ADHF management from a preoccupation with salt restriction to focus more on fighting fluid retention.

OSPREY-HF took on “an established practice that doesn’t have much high-quality evidentiary support,” one guided primarily by consensus and observational data, Montgomery said in an interview.

There are also potential downsides to dietary sodium restriction, including some that may complicate or block ADHF therapies.

“Low-sodium diets can be associated with decreased caloric intake and nutritional quality,” Dr. Montgomery observed. And observational studies suggest that “patients who are on a low sodium diet can develop increased neurohormonal activation. The kidney is not sensing salt, and so starts ramping up the hormones,” which promotes diuretic resistance.

But emerging evidence also suggests “that giving sodium chloride in the form of hypertonic saline can help patients who are diuretic resistant.” The intervention, which appears to attenuate the neurohormonal activation associated with high-dose intravenous diuretics, Dr. Montgomery noted, helped inspire the design of OSPREY-AHF.

Edema consists of “a gallon of water and a pinch of salt, so we really should stop being so salt-centric and think much more about water as the problem in decompensated heart failure,” said John G.F. Cleland, MD, PhD, during the question-and-answer period after Montgomery’s presentation. Dr. Cleland, of the University of Glasgow Institute of Health and Wellbeing, is not connected to OSPREY-AHF.

“I think that maybe we overinterpret how important salt is” as a focus of volume management in ADHF, offered David Lanfear, MD, Henry Ford Health System, Detroit, who is also not part of the study.

OSPREY-AHF was well conducted but applies to a “very specific” clinical setting, Dr. Lanfear said in an interview. “These people are getting aggressive diuresis, a big dose and continuous infusion. It’s not everybody that has heart failure.”

Although the study was small, “I think it will fuel interest in this area and, probably, further investigation,” he said. The trial on its own won’t change practice, “but it will raise some eyebrows.”

The trial included patients with ADHF who have been “admitted to a cardiovascular medicine floor, not the intensive care unit” and were receiving at least 10 mg per hour of furosemide. It excluded any who were “hypernatremic or severely hyponatremic,” said Dr. Montgomery when presenting the study. They were required to have an initial estimated glomerular filtration rate (eGFR) of at least 15 mL/min per 1.73 m².

The patients were randomly assigned double blind at a single center to receive tablets providing 2 g sodium chloride or placebo pills – 34 and 31 patients, respectively – three times daily during intravenous diuresis.

At 96 hours, the two groups showed no difference in change in creatinine levels or change in weight, both primary endpoints. Nor did they differ in urine output or change in eGFR. But serum sodium levels fell further, and BUN levels went up more in those given placebo.

The two groups showed no differences in hospital length of stay, use of renal replacement therapy at 90 days, ICU time during the index hospitalization, 30-day readmission, or 90-day mortality – although the trial wasn’t powered for clinical outcomes, Dr. Montgomery reported.

"We have patients who complain about their sodium-restricted diet, we have patients that have cachexia, who have a lot of complaints about provider-ordered meals and recommendations,” Dr. Montgomery explained in an interview.

Clinicians provide education and invest a lot of effort into getting patients with heart failure to start and maintain a low-sodium diet, he said. “But a low-sodium diet, in prior studies – and our study adds to this – is not a lever that actually seems to positively or adversely affect patients.”

Dr. Montgomery pointed to the recently published SODIUM-HF trial comparing low-sodium and unrestricted-sodium diets in outpatients with heart failure. It saw no clinical benefit from the low-sodium intervention.

Until studies show, potentially, that sodium restriction in hospitalized patients with heart failure makes a clinical difference, Dr. Montgomery said, “I’d say we should invest our time in things that we know are the most helpful, like getting them on guideline-directed medical therapy, when instead we spend an enormous amount of time counseling on and enforcing dietary restriction.”

Support for this study was provided by Cleveland Clinic Heart Vascular and Thoracic Institute’s Wilson Grant and Kaufman Center for Heart Failure Treatment and Recovery Grant. Dr. Lanfear disclosed research support from SomaLogic and Lilly; consulting for Abbott Laboratories, AstraZeneca, Janssen, Martin Pharmaceuticals, and Amgen; and serving on advisory panels for Illumina and Cytokinetics. Dr. Montgomery and Dr. Cleland disclosed no relevant financial relationships.

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

To be cost effective, compared with metformin, for initial therapy for type 2 diabetes, prices for a sodium-glucose cotransporter-2 (SGLT2) inhibitor or a glucagon-like peptide-1 (GLP-1) agonist would have to fall by at least 70% and at least 90%, respectively, according to estimates.

Thinkstock Photos

The study, modeled on U.S. patients, by Jin G. Choi, MD, and colleagues, was published online Oct. 3 in the Annals of Internal Medicine.

The researchers simulated the lifetime incidence, prevalence, mortality, and costs associated with three different first-line treatment strategies – metformin, an SGLT2 inhibitor, or a GLP-1 agonist – in U.S. patients with untreated type 2 diabetes.

Compared with patients who received initial treatment with metformin, those who received one of the newer drugs had 4.4% to 5.2% lower lifetime rates of congestive heart failure, ischemic heart disease, myocardial infarction, and stroke.

However, to be cost-effective at under $150,000 per quality-adjusted life-years (QALY), SGLT2 inhibitors would need to cost less than $5 a day ($1,800 a year), and GLP-1 agonists would have to cost less than $6 a day ($2,100 a year), a lot less than now.

Knowing how expensive these drugs are, “I am not surprised” that the model predicts that the price would have to drop so much to make them cost-effective, compared with first-line treatment with metformin, senior author Neda Laiteerapong, MD, said in an interview.

“But I am disappointed,” she said, because these drugs are very effective, and if the prices were lower, more people could benefit.

“In the interest of improving access to high-quality care in the United States, our study results indicate the need to reduce SGLT2 inhibitor and GLP-1 receptor agonist medication costs substantially for patients with type 2 [diabetes] to improve health outcomes and prevent exacerbating diabetes health disparities,” the researchers conclude.

One way that the newer drugs might be more widely affordable is if the government became involved, possibly by passing a law similar to the Affordable Insulin Now Act, speculated Dr. Laiteerapong, who is associate director at the Center for Chronic Disease Research and Policy, University of Chicago.
 

‘Current prices too high to encourage first-line adoption’

Guidelines recommend the use of SGLT2 inhibitors and GLP-1 agonists as second-line therapies for patients with type 2 diabetes, but it has not been clear if clinical benefits would outweigh costs for use as first-line therapies.

“Although clinical trials have demonstrated the clinical effectiveness of these newer drugs, they are hundreds of times more expensive than other ... diabetes drugs,” the researchers note.

On the other hand, costs may fall in the coming years when these new drugs come off-patent.

The current study was designed to help inform future clinical guidelines.

The researchers created a population simulation model based on the United Kingdom Prospective Diabetes Study, Outcomes Model version 2 (UKPDS OM2) for diabetes-related complications and mortality, with added information about hypoglycemic events, quality of life, and U.S. costs. 

The researchers also identified a nationally representative sample of people who would be eligible to start first-line diabetes therapy when their A1c reached 7% for the model. 

Using National Health and Nutrition Examination Survey (NHANES) data (2013-2016), the researchers identified about 7.3 million U.S. adults aged 18 and older with self-reported diabetes or an A1c greater than 6.5% with no reported use of diabetes medications.

Patients were an average age of 55, and 55% were women. They had had diabetes for an average of 4.2 years, and 36% had a history of diabetes complications.

The model projected that patients would have an improved life expectancy of 3.0 and 3.4 months from first-line SGLT2 inhibitors and GLP-1 agonists, respectively, compared with initial therapy with metformin due to reduced rates of macrovascular disease.  

“However, the current drug costs would be too high to encourage their adoption as first-line for usual clinical practice,” the researchers report.
 

‘Disparities could remain for decades’

Generic SGLT2 inhibitors could enter the marketplace shortly, because one of two dapagliflozin patents expired in October 2020 and approval for generic alternatives has been sought from the U.S. Food and Drug Administration, Dr. Choi and colleagues note.

However, it could still take decades for medication prices to drop low enough to become affordable, the group cautions. For example, a generic GLP-1 agonist became available in 2017, but costs remain high.

“Without external incentives,” the group writes, “limited access to these drug classes will likely persist (for example, due to higher copays or requirements for prior authorizations), as will further diabetes disparities – for decades into the future – because of differential access to care due to insurance (for example, private vs. public), which often tracks race and ethnicity.”

The study was supported by the American Diabetes Association. Dr. Choi was supported by a National Institutes of Health, National Institute on Aging grant. Dr. Laiteerapong and other co-authors are members of the National Institute of Diabetes and Digestive and Kidney Diseases Chicago Center for Diabetes Translation Research at the University of Chicago. Dr. Choi and Dr. Laiteerapong have reported no relevant financial relationships.

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

To be cost effective, compared with metformin, for initial therapy for type 2 diabetes, prices for a sodium-glucose cotransporter-2 (SGLT2) inhibitor or a glucagon-like peptide-1 (GLP-1) agonist would have to fall by at least 70% and at least 90%, respectively, according to estimates.

Thinkstock Photos

The study, modeled on U.S. patients, by Jin G. Choi, MD, and colleagues, was published online Oct. 3 in the Annals of Internal Medicine.

The researchers simulated the lifetime incidence, prevalence, mortality, and costs associated with three different first-line treatment strategies – metformin, an SGLT2 inhibitor, or a GLP-1 agonist – in U.S. patients with untreated type 2 diabetes.

Compared with patients who received initial treatment with metformin, those who received one of the newer drugs had 4.4% to 5.2% lower lifetime rates of congestive heart failure, ischemic heart disease, myocardial infarction, and stroke.

However, to be cost-effective at under $150,000 per quality-adjusted life-years (QALY), SGLT2 inhibitors would need to cost less than $5 a day ($1,800 a year), and GLP-1 agonists would have to cost less than $6 a day ($2,100 a year), a lot less than now.

Knowing how expensive these drugs are, “I am not surprised” that the model predicts that the price would have to drop so much to make them cost-effective, compared with first-line treatment with metformin, senior author Neda Laiteerapong, MD, said in an interview.

“But I am disappointed,” she said, because these drugs are very effective, and if the prices were lower, more people could benefit.

“In the interest of improving access to high-quality care in the United States, our study results indicate the need to reduce SGLT2 inhibitor and GLP-1 receptor agonist medication costs substantially for patients with type 2 [diabetes] to improve health outcomes and prevent exacerbating diabetes health disparities,” the researchers conclude.

One way that the newer drugs might be more widely affordable is if the government became involved, possibly by passing a law similar to the Affordable Insulin Now Act, speculated Dr. Laiteerapong, who is associate director at the Center for Chronic Disease Research and Policy, University of Chicago.
 

‘Current prices too high to encourage first-line adoption’

Guidelines recommend the use of SGLT2 inhibitors and GLP-1 agonists as second-line therapies for patients with type 2 diabetes, but it has not been clear if clinical benefits would outweigh costs for use as first-line therapies.

“Although clinical trials have demonstrated the clinical effectiveness of these newer drugs, they are hundreds of times more expensive than other ... diabetes drugs,” the researchers note.

On the other hand, costs may fall in the coming years when these new drugs come off-patent.

The current study was designed to help inform future clinical guidelines.

The researchers created a population simulation model based on the United Kingdom Prospective Diabetes Study, Outcomes Model version 2 (UKPDS OM2) for diabetes-related complications and mortality, with added information about hypoglycemic events, quality of life, and U.S. costs. 

The researchers also identified a nationally representative sample of people who would be eligible to start first-line diabetes therapy when their A1c reached 7% for the model. 

Using National Health and Nutrition Examination Survey (NHANES) data (2013-2016), the researchers identified about 7.3 million U.S. adults aged 18 and older with self-reported diabetes or an A1c greater than 6.5% with no reported use of diabetes medications.

Patients were an average age of 55, and 55% were women. They had had diabetes for an average of 4.2 years, and 36% had a history of diabetes complications.

The model projected that patients would have an improved life expectancy of 3.0 and 3.4 months from first-line SGLT2 inhibitors and GLP-1 agonists, respectively, compared with initial therapy with metformin due to reduced rates of macrovascular disease.  

“However, the current drug costs would be too high to encourage their adoption as first-line for usual clinical practice,” the researchers report.
 

‘Disparities could remain for decades’

Generic SGLT2 inhibitors could enter the marketplace shortly, because one of two dapagliflozin patents expired in October 2020 and approval for generic alternatives has been sought from the U.S. Food and Drug Administration, Dr. Choi and colleagues note.

However, it could still take decades for medication prices to drop low enough to become affordable, the group cautions. For example, a generic GLP-1 agonist became available in 2017, but costs remain high.

“Without external incentives,” the group writes, “limited access to these drug classes will likely persist (for example, due to higher copays or requirements for prior authorizations), as will further diabetes disparities – for decades into the future – because of differential access to care due to insurance (for example, private vs. public), which often tracks race and ethnicity.”

The study was supported by the American Diabetes Association. Dr. Choi was supported by a National Institutes of Health, National Institute on Aging grant. Dr. Laiteerapong and other co-authors are members of the National Institute of Diabetes and Digestive and Kidney Diseases Chicago Center for Diabetes Translation Research at the University of Chicago. Dr. Choi and Dr. Laiteerapong have reported no relevant financial relationships.

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

To be cost effective, compared with metformin, for initial therapy for type 2 diabetes, prices for a sodium-glucose cotransporter-2 (SGLT2) inhibitor or a glucagon-like peptide-1 (GLP-1) agonist would have to fall by at least 70% and at least 90%, respectively, according to estimates.

Thinkstock Photos

The study, modeled on U.S. patients, by Jin G. Choi, MD, and colleagues, was published online Oct. 3 in the Annals of Internal Medicine.

The researchers simulated the lifetime incidence, prevalence, mortality, and costs associated with three different first-line treatment strategies – metformin, an SGLT2 inhibitor, or a GLP-1 agonist – in U.S. patients with untreated type 2 diabetes.

Compared with patients who received initial treatment with metformin, those who received one of the newer drugs had 4.4% to 5.2% lower lifetime rates of congestive heart failure, ischemic heart disease, myocardial infarction, and stroke.

However, to be cost-effective at under $150,000 per quality-adjusted life-years (QALY), SGLT2 inhibitors would need to cost less than $5 a day ($1,800 a year), and GLP-1 agonists would have to cost less than $6 a day ($2,100 a year), a lot less than now.

Knowing how expensive these drugs are, “I am not surprised” that the model predicts that the price would have to drop so much to make them cost-effective, compared with first-line treatment with metformin, senior author Neda Laiteerapong, MD, said in an interview.

“But I am disappointed,” she said, because these drugs are very effective, and if the prices were lower, more people could benefit.

“In the interest of improving access to high-quality care in the United States, our study results indicate the need to reduce SGLT2 inhibitor and GLP-1 receptor agonist medication costs substantially for patients with type 2 [diabetes] to improve health outcomes and prevent exacerbating diabetes health disparities,” the researchers conclude.

One way that the newer drugs might be more widely affordable is if the government became involved, possibly by passing a law similar to the Affordable Insulin Now Act, speculated Dr. Laiteerapong, who is associate director at the Center for Chronic Disease Research and Policy, University of Chicago.
 

‘Current prices too high to encourage first-line adoption’

Guidelines recommend the use of SGLT2 inhibitors and GLP-1 agonists as second-line therapies for patients with type 2 diabetes, but it has not been clear if clinical benefits would outweigh costs for use as first-line therapies.

“Although clinical trials have demonstrated the clinical effectiveness of these newer drugs, they are hundreds of times more expensive than other ... diabetes drugs,” the researchers note.

On the other hand, costs may fall in the coming years when these new drugs come off-patent.

The current study was designed to help inform future clinical guidelines.

The researchers created a population simulation model based on the United Kingdom Prospective Diabetes Study, Outcomes Model version 2 (UKPDS OM2) for diabetes-related complications and mortality, with added information about hypoglycemic events, quality of life, and U.S. costs. 

The researchers also identified a nationally representative sample of people who would be eligible to start first-line diabetes therapy when their A1c reached 7% for the model. 

Using National Health and Nutrition Examination Survey (NHANES) data (2013-2016), the researchers identified about 7.3 million U.S. adults aged 18 and older with self-reported diabetes or an A1c greater than 6.5% with no reported use of diabetes medications.

Patients were an average age of 55, and 55% were women. They had had diabetes for an average of 4.2 years, and 36% had a history of diabetes complications.

The model projected that patients would have an improved life expectancy of 3.0 and 3.4 months from first-line SGLT2 inhibitors and GLP-1 agonists, respectively, compared with initial therapy with metformin due to reduced rates of macrovascular disease.  

“However, the current drug costs would be too high to encourage their adoption as first-line for usual clinical practice,” the researchers report.
 

‘Disparities could remain for decades’

Generic SGLT2 inhibitors could enter the marketplace shortly, because one of two dapagliflozin patents expired in October 2020 and approval for generic alternatives has been sought from the U.S. Food and Drug Administration, Dr. Choi and colleagues note.

However, it could still take decades for medication prices to drop low enough to become affordable, the group cautions. For example, a generic GLP-1 agonist became available in 2017, but costs remain high.

“Without external incentives,” the group writes, “limited access to these drug classes will likely persist (for example, due to higher copays or requirements for prior authorizations), as will further diabetes disparities – for decades into the future – because of differential access to care due to insurance (for example, private vs. public), which often tracks race and ethnicity.”

The study was supported by the American Diabetes Association. Dr. Choi was supported by a National Institutes of Health, National Institute on Aging grant. Dr. Laiteerapong and other co-authors are members of the National Institute of Diabetes and Digestive and Kidney Diseases Chicago Center for Diabetes Translation Research at the University of Chicago. Dr. Choi and Dr. Laiteerapong have reported no relevant financial relationships.

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

A growing number of Americans with cardiovascular disease (CVD) have limited or uncertain access to food, results of a new study suggest.

An analysis of data from the National Health and Nutrition Examination Survey (NHANES) representing more than 300 million American adults found that, overall, 38.1% of people with cardiovascular disease were food insecure in 2017-2019.

©Amanda Grandfield/iStockphoto.com

Uphill battle

Johanna Contreras, MD, advanced heart failure and transplant cardiologist at the Mount Sinai Hospital, New York, treats food insecure cardiovascular patients in her practice and tries to educate them about good nutrition. But it is an uphill battle.

“A lot of my patients live in the South Bronx. They have hypertension, hypercholesterolemia, and there are no grocery stores where they can buy fresh vegetables. I talk to them about eating healthy. They tell me it’s impossible. The stores only have pre-packaged foods. So even in the South Bronx, even though it is in New York, it is very hard to get fresh food. And when it is available, it is very expensive,” Dr. Contreras told this news organization.

“Fresh pineapples can cost $8. A fast-food burger costs $3. So that is what they buy: It’s what they can afford. Even the store managers don’t want to stock fresh produce because it can spoil. They open stores, like Whole Foods, but in the more affluent neighborhoods. They should open one in poor neighborhoods,” she said.

Dr. Contreras says she spends much of her time educating her patients about good nutrition. She asks them to keep a food diary and analyzes the results at each visit.

“I look at what they eat, and I try to see how I can use this information in a good way. I advise them to use frozen foods, and avoid canned, because it is a lot healthier. I am pragmatic, because I know that if I tell my patients to eat salmon, for example, they aren’t going to be able to afford it, if they can even access it.”

She also informs them about relatively healthy fast-food choices.

“I tell them to order 100% fruit juice, water, or milk when they go to McDonalds or other fast-food places. So I think this study is very important. Food insecurity is a very important component of cardiovascular disease, and unfortunately, minority communities are where this occurs.”

Dr. Brandt and Dr. Contreras report no relevant financial relationships.

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

A growing number of Americans with cardiovascular disease (CVD) have limited or uncertain access to food, results of a new study suggest.

An analysis of data from the National Health and Nutrition Examination Survey (NHANES) representing more than 300 million American adults found that, overall, 38.1% of people with cardiovascular disease were food insecure in 2017-2019.

©Amanda Grandfield/iStockphoto.com

Uphill battle

Johanna Contreras, MD, advanced heart failure and transplant cardiologist at the Mount Sinai Hospital, New York, treats food insecure cardiovascular patients in her practice and tries to educate them about good nutrition. But it is an uphill battle.

“A lot of my patients live in the South Bronx. They have hypertension, hypercholesterolemia, and there are no grocery stores where they can buy fresh vegetables. I talk to them about eating healthy. They tell me it’s impossible. The stores only have pre-packaged foods. So even in the South Bronx, even though it is in New York, it is very hard to get fresh food. And when it is available, it is very expensive,” Dr. Contreras told this news organization.

“Fresh pineapples can cost $8. A fast-food burger costs $3. So that is what they buy: It’s what they can afford. Even the store managers don’t want to stock fresh produce because it can spoil. They open stores, like Whole Foods, but in the more affluent neighborhoods. They should open one in poor neighborhoods,” she said.

Dr. Contreras says she spends much of her time educating her patients about good nutrition. She asks them to keep a food diary and analyzes the results at each visit.

“I look at what they eat, and I try to see how I can use this information in a good way. I advise them to use frozen foods, and avoid canned, because it is a lot healthier. I am pragmatic, because I know that if I tell my patients to eat salmon, for example, they aren’t going to be able to afford it, if they can even access it.”

She also informs them about relatively healthy fast-food choices.

“I tell them to order 100% fruit juice, water, or milk when they go to McDonalds or other fast-food places. So I think this study is very important. Food insecurity is a very important component of cardiovascular disease, and unfortunately, minority communities are where this occurs.”

Dr. Brandt and Dr. Contreras report no relevant financial relationships.

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

A growing number of Americans with cardiovascular disease (CVD) have limited or uncertain access to food, results of a new study suggest.

An analysis of data from the National Health and Nutrition Examination Survey (NHANES) representing more than 300 million American adults found that, overall, 38.1% of people with cardiovascular disease were food insecure in 2017-2019.

©Amanda Grandfield/iStockphoto.com

Uphill battle

Johanna Contreras, MD, advanced heart failure and transplant cardiologist at the Mount Sinai Hospital, New York, treats food insecure cardiovascular patients in her practice and tries to educate them about good nutrition. But it is an uphill battle.

“A lot of my patients live in the South Bronx. They have hypertension, hypercholesterolemia, and there are no grocery stores where they can buy fresh vegetables. I talk to them about eating healthy. They tell me it’s impossible. The stores only have pre-packaged foods. So even in the South Bronx, even though it is in New York, it is very hard to get fresh food. And when it is available, it is very expensive,” Dr. Contreras told this news organization.

“Fresh pineapples can cost $8. A fast-food burger costs $3. So that is what they buy: It’s what they can afford. Even the store managers don’t want to stock fresh produce because it can spoil. They open stores, like Whole Foods, but in the more affluent neighborhoods. They should open one in poor neighborhoods,” she said.

Dr. Contreras says she spends much of her time educating her patients about good nutrition. She asks them to keep a food diary and analyzes the results at each visit.

“I look at what they eat, and I try to see how I can use this information in a good way. I advise them to use frozen foods, and avoid canned, because it is a lot healthier. I am pragmatic, because I know that if I tell my patients to eat salmon, for example, they aren’t going to be able to afford it, if they can even access it.”

She also informs them about relatively healthy fast-food choices.

“I tell them to order 100% fruit juice, water, or milk when they go to McDonalds or other fast-food places. So I think this study is very important. Food insecurity is a very important component of cardiovascular disease, and unfortunately, minority communities are where this occurs.”

Dr. Brandt and Dr. Contreras report no relevant financial relationships.

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

Transplantation of hearts donated after circulatory death (DCD) is associated with short-term clinical outcomes similar to those of hearts donated after brain death (DBD), except for transient posttransplant right heart dysfunction, a single-center analysis suggests.

The right-heart dysfunction resolved by 3 weeks post transplant, and recipient mortality was similar for those receiving DCD and DBD, which is considered standard of care (SOC).

Furthermore, the median waiting list time was significantly shorter for DCD recipients than for SOC recipients (17 vs. 70 days).

The authors suggest that use of DCD hearts could expand the donor pool by as much as 30%.

“Now that we and others have demonstrated the safety of this technique, I believe it is our obligation as a transplant community to use these organs and not allow them to be wasted,” David A. D’Alessandro, MD, of Massachusetts General Hospital, Boston, told this news organization.

“I will caution that DCD heart transplantation is labor intensive, and there is a learning curve which can potentially put patients at risk,” he added. “It is vitally important, therefore, that we learn from each other’s experiences to flatten this curve.”

The study was published online in the Journal of the American College of Cardiology.
 

Similar outcomes

Dr. D’Alessandro and colleagues compared the hemodynamic and clinical profiles of 47 DCD hearts with 166 SOC hearts implanted at Massachusetts General Hospital between 2016 and 2022. DCD hearts were maintained with use of a proprietary warm perfusion circuit organ care system (OCS, TransMedics).

Baseline characteristics were similar between the groups, except the DCD heart recipients were younger (mean age, 55 vs. 59); they were less likely to be an inpatient at the time of transplant (26% vs. 49%); and they had lower pulmonary vascular resistance (1.73 WU vs. 2.26 WU).

The median time from DCD consent to transplant was significantly shorter than for SOC hearts (17 vs. 70 days). However, there was a higher, though not statistically significant, incidence of severe primary graft dysfunction at 24 hours post transplant with DCD (10.6% vs. SOC 3.6%), leading five DCD recipients (10.6%) and nine SOC recipients (5.4%) to receive venoarterial extracorporeal membrane oxygenation.

Right heart function was significantly impaired in DCD vs. SOC recipients 1 week post transplant, with higher median right atrial pressure (10 mm Hg vs. 7 mm Hg); higher right atrial pressure to pulmonary capillary wedge pressure ratio (0.64 vs. 0.57); and lower pulmonary arterial pulsatility index (1.66 vs. 2.52).

However, by 3 weeks post transplant, right heart function was similar between the groups, as was mortality at 30 days (0 vs. 2%) and 1 year (3% vs. 8%).

Furthermore, hospital length of stay following transplant, intensive care unit length of stay, ICU readmissions, and 30-day readmissions were similar between the groups.

“We and others will continue to push the boundaries of this technique to understand if we can safely extend the warm ischemic time, which could make additional organs available,” Dr. D’Alessandro said. “We will also be exploring additional ways to monitor and assess organ health and viability ex situ and potential avenues of treatment which could repair and optimize organ function.

“A successful DCD heart transplant program requires institutional and team commitment,” he added, “and there are clinical nuances which should be appreciated to minimize patient risks associated with the obligate learning curve.”

Ulrich P. Jorde, MD, of Montefiore Medical Center in New York, author of a related editorial, concluded that heart donation after circulatory death “promises significant expansion of the donor pool and will lead to many lives saved” and that “the current investigation is a timely and important contribution to this effort”.

However, he noted, “it must be acknowledged that donation after cardiac death has evoked significant controversy regarding the ethics of this approach,” particularly when using a technique called normothermic regional perfusion (NRP), in which, after declaration of death and ligation of cerebral vessels, the heart is resuscitated in situ using extracorporeal membrane oxygenation, as opposed to the proprietary warm perfusion OCS used in this study.

“Central to this discussion is the definition of death and its irreversibility,” Dr. Jorde noted. “In contrast to DBD, where brain death protocols are well established and accepted by societies across the globe, DCD protocol rules, e.g., standoff times after complete cessation of circulation, continue to vary even within national jurisdictions. Such variability and incomplete standardization of practice is particularly important when the organ is resuscitated in situ using normothermic regional perfusion.

“The International Society of Heart and Lung Transplantation has recently provided a framework within which donation after cardiac death, with or without the use of NRP, can be conducted to comply with ethical and legal norms and regulations, acknowledging that such norms and regulations may differ between societies,” he wrote. “To advance the field, and to ensure ongoing trust in the transplantation system, it is of critical importance that such discussions are held publicly and transparently.”
 

More ‘dry runs’

“Donor heart allographs are safe for our patients with heart failure if procured and transplanted in an organized and protocolized manner,” Philip J. Spencer, MD, a cardiovascular and transplant surgeon at Mayo Clinic in Rochester, Minn., told this news organization. “As the techniques are adopted globally, our patients will benefit.”

Nevertheless, like Dr. D’Alessandro, he noted that procurement of DCD hearts is more labor intensive. “A program and its patients must be willing to accept a higher number of ‘dry runs,’ which occurs when the team is sent for an organ and the donor does not progress to circulatory death in a time and manner appropriate for safe organ recovery.

“There is no doubt that being open to these organs will increase the patient’s chances of receiving a donor heart in a shorter period of time,” he said. “However, the experience of a dry run, or multiple, can be emotionally and financially stressful for the patient and the program.”

No commercial funding or relevant conflicts of interest were disclosed.

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

Transplantation of hearts donated after circulatory death (DCD) is associated with short-term clinical outcomes similar to those of hearts donated after brain death (DBD), except for transient posttransplant right heart dysfunction, a single-center analysis suggests.

The right-heart dysfunction resolved by 3 weeks post transplant, and recipient mortality was similar for those receiving DCD and DBD, which is considered standard of care (SOC).

Furthermore, the median waiting list time was significantly shorter for DCD recipients than for SOC recipients (17 vs. 70 days).

The authors suggest that use of DCD hearts could expand the donor pool by as much as 30%.

“Now that we and others have demonstrated the safety of this technique, I believe it is our obligation as a transplant community to use these organs and not allow them to be wasted,” David A. D’Alessandro, MD, of Massachusetts General Hospital, Boston, told this news organization.

“I will caution that DCD heart transplantation is labor intensive, and there is a learning curve which can potentially put patients at risk,” he added. “It is vitally important, therefore, that we learn from each other’s experiences to flatten this curve.”

The study was published online in the Journal of the American College of Cardiology.
 

Similar outcomes

Dr. D’Alessandro and colleagues compared the hemodynamic and clinical profiles of 47 DCD hearts with 166 SOC hearts implanted at Massachusetts General Hospital between 2016 and 2022. DCD hearts were maintained with use of a proprietary warm perfusion circuit organ care system (OCS, TransMedics).

Baseline characteristics were similar between the groups, except the DCD heart recipients were younger (mean age, 55 vs. 59); they were less likely to be an inpatient at the time of transplant (26% vs. 49%); and they had lower pulmonary vascular resistance (1.73 WU vs. 2.26 WU).

The median time from DCD consent to transplant was significantly shorter than for SOC hearts (17 vs. 70 days). However, there was a higher, though not statistically significant, incidence of severe primary graft dysfunction at 24 hours post transplant with DCD (10.6% vs. SOC 3.6%), leading five DCD recipients (10.6%) and nine SOC recipients (5.4%) to receive venoarterial extracorporeal membrane oxygenation.

Right heart function was significantly impaired in DCD vs. SOC recipients 1 week post transplant, with higher median right atrial pressure (10 mm Hg vs. 7 mm Hg); higher right atrial pressure to pulmonary capillary wedge pressure ratio (0.64 vs. 0.57); and lower pulmonary arterial pulsatility index (1.66 vs. 2.52).

However, by 3 weeks post transplant, right heart function was similar between the groups, as was mortality at 30 days (0 vs. 2%) and 1 year (3% vs. 8%).

Furthermore, hospital length of stay following transplant, intensive care unit length of stay, ICU readmissions, and 30-day readmissions were similar between the groups.

“We and others will continue to push the boundaries of this technique to understand if we can safely extend the warm ischemic time, which could make additional organs available,” Dr. D’Alessandro said. “We will also be exploring additional ways to monitor and assess organ health and viability ex situ and potential avenues of treatment which could repair and optimize organ function.

“A successful DCD heart transplant program requires institutional and team commitment,” he added, “and there are clinical nuances which should be appreciated to minimize patient risks associated with the obligate learning curve.”

Ulrich P. Jorde, MD, of Montefiore Medical Center in New York, author of a related editorial, concluded that heart donation after circulatory death “promises significant expansion of the donor pool and will lead to many lives saved” and that “the current investigation is a timely and important contribution to this effort”.

However, he noted, “it must be acknowledged that donation after cardiac death has evoked significant controversy regarding the ethics of this approach,” particularly when using a technique called normothermic regional perfusion (NRP), in which, after declaration of death and ligation of cerebral vessels, the heart is resuscitated in situ using extracorporeal membrane oxygenation, as opposed to the proprietary warm perfusion OCS used in this study.

“Central to this discussion is the definition of death and its irreversibility,” Dr. Jorde noted. “In contrast to DBD, where brain death protocols are well established and accepted by societies across the globe, DCD protocol rules, e.g., standoff times after complete cessation of circulation, continue to vary even within national jurisdictions. Such variability and incomplete standardization of practice is particularly important when the organ is resuscitated in situ using normothermic regional perfusion.

“The International Society of Heart and Lung Transplantation has recently provided a framework within which donation after cardiac death, with or without the use of NRP, can be conducted to comply with ethical and legal norms and regulations, acknowledging that such norms and regulations may differ between societies,” he wrote. “To advance the field, and to ensure ongoing trust in the transplantation system, it is of critical importance that such discussions are held publicly and transparently.”
 

More ‘dry runs’

“Donor heart allographs are safe for our patients with heart failure if procured and transplanted in an organized and protocolized manner,” Philip J. Spencer, MD, a cardiovascular and transplant surgeon at Mayo Clinic in Rochester, Minn., told this news organization. “As the techniques are adopted globally, our patients will benefit.”

Nevertheless, like Dr. D’Alessandro, he noted that procurement of DCD hearts is more labor intensive. “A program and its patients must be willing to accept a higher number of ‘dry runs,’ which occurs when the team is sent for an organ and the donor does not progress to circulatory death in a time and manner appropriate for safe organ recovery.

“There is no doubt that being open to these organs will increase the patient’s chances of receiving a donor heart in a shorter period of time,” he said. “However, the experience of a dry run, or multiple, can be emotionally and financially stressful for the patient and the program.”

No commercial funding or relevant conflicts of interest were disclosed.

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

Transplantation of hearts donated after circulatory death (DCD) is associated with short-term clinical outcomes similar to those of hearts donated after brain death (DBD), except for transient posttransplant right heart dysfunction, a single-center analysis suggests.

The right-heart dysfunction resolved by 3 weeks post transplant, and recipient mortality was similar for those receiving DCD and DBD, which is considered standard of care (SOC).

Furthermore, the median waiting list time was significantly shorter for DCD recipients than for SOC recipients (17 vs. 70 days).

The authors suggest that use of DCD hearts could expand the donor pool by as much as 30%.

“Now that we and others have demonstrated the safety of this technique, I believe it is our obligation as a transplant community to use these organs and not allow them to be wasted,” David A. D’Alessandro, MD, of Massachusetts General Hospital, Boston, told this news organization.

“I will caution that DCD heart transplantation is labor intensive, and there is a learning curve which can potentially put patients at risk,” he added. “It is vitally important, therefore, that we learn from each other’s experiences to flatten this curve.”

The study was published online in the Journal of the American College of Cardiology.
 

Similar outcomes

Dr. D’Alessandro and colleagues compared the hemodynamic and clinical profiles of 47 DCD hearts with 166 SOC hearts implanted at Massachusetts General Hospital between 2016 and 2022. DCD hearts were maintained with use of a proprietary warm perfusion circuit organ care system (OCS, TransMedics).

Baseline characteristics were similar between the groups, except the DCD heart recipients were younger (mean age, 55 vs. 59); they were less likely to be an inpatient at the time of transplant (26% vs. 49%); and they had lower pulmonary vascular resistance (1.73 WU vs. 2.26 WU).

The median time from DCD consent to transplant was significantly shorter than for SOC hearts (17 vs. 70 days). However, there was a higher, though not statistically significant, incidence of severe primary graft dysfunction at 24 hours post transplant with DCD (10.6% vs. SOC 3.6%), leading five DCD recipients (10.6%) and nine SOC recipients (5.4%) to receive venoarterial extracorporeal membrane oxygenation.

Right heart function was significantly impaired in DCD vs. SOC recipients 1 week post transplant, with higher median right atrial pressure (10 mm Hg vs. 7 mm Hg); higher right atrial pressure to pulmonary capillary wedge pressure ratio (0.64 vs. 0.57); and lower pulmonary arterial pulsatility index (1.66 vs. 2.52).

However, by 3 weeks post transplant, right heart function was similar between the groups, as was mortality at 30 days (0 vs. 2%) and 1 year (3% vs. 8%).

Furthermore, hospital length of stay following transplant, intensive care unit length of stay, ICU readmissions, and 30-day readmissions were similar between the groups.

“We and others will continue to push the boundaries of this technique to understand if we can safely extend the warm ischemic time, which could make additional organs available,” Dr. D’Alessandro said. “We will also be exploring additional ways to monitor and assess organ health and viability ex situ and potential avenues of treatment which could repair and optimize organ function.

“A successful DCD heart transplant program requires institutional and team commitment,” he added, “and there are clinical nuances which should be appreciated to minimize patient risks associated with the obligate learning curve.”

Ulrich P. Jorde, MD, of Montefiore Medical Center in New York, author of a related editorial, concluded that heart donation after circulatory death “promises significant expansion of the donor pool and will lead to many lives saved” and that “the current investigation is a timely and important contribution to this effort”.

However, he noted, “it must be acknowledged that donation after cardiac death has evoked significant controversy regarding the ethics of this approach,” particularly when using a technique called normothermic regional perfusion (NRP), in which, after declaration of death and ligation of cerebral vessels, the heart is resuscitated in situ using extracorporeal membrane oxygenation, as opposed to the proprietary warm perfusion OCS used in this study.

“Central to this discussion is the definition of death and its irreversibility,” Dr. Jorde noted. “In contrast to DBD, where brain death protocols are well established and accepted by societies across the globe, DCD protocol rules, e.g., standoff times after complete cessation of circulation, continue to vary even within national jurisdictions. Such variability and incomplete standardization of practice is particularly important when the organ is resuscitated in situ using normothermic regional perfusion.

“The International Society of Heart and Lung Transplantation has recently provided a framework within which donation after cardiac death, with or without the use of NRP, can be conducted to comply with ethical and legal norms and regulations, acknowledging that such norms and regulations may differ between societies,” he wrote. “To advance the field, and to ensure ongoing trust in the transplantation system, it is of critical importance that such discussions are held publicly and transparently.”
 

More ‘dry runs’

“Donor heart allographs are safe for our patients with heart failure if procured and transplanted in an organized and protocolized manner,” Philip J. Spencer, MD, a cardiovascular and transplant surgeon at Mayo Clinic in Rochester, Minn., told this news organization. “As the techniques are adopted globally, our patients will benefit.”

Nevertheless, like Dr. D’Alessandro, he noted that procurement of DCD hearts is more labor intensive. “A program and its patients must be willing to accept a higher number of ‘dry runs,’ which occurs when the team is sent for an organ and the donor does not progress to circulatory death in a time and manner appropriate for safe organ recovery.

“There is no doubt that being open to these organs will increase the patient’s chances of receiving a donor heart in a shorter period of time,” he said. “However, the experience of a dry run, or multiple, can be emotionally and financially stressful for the patient and the program.”

No commercial funding or relevant conflicts of interest were disclosed.

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

STOCKHOLM – Recent study results confirm that two agents from the sodium-glucose cotransporter 2 (SGLT2) inhibitor class can significantly cut the incidence of adverse cardiovascular events in patients with heart failure with reduced ejection fraction (HFpEF), a disease especially common in people with type 2 diabetes, obesity, or both.

And findings from secondary analyses of the studies – including one reported at the annual meeting of the European Association for the Study of Diabetes – show that these SGLT2 inhibitors work as well for cutting incident adverse events (cardiovascular death or worsening heart failure) in patients with HFpEF and diabetes as they do for people with normal blood glucose levels.

But delivering treatment with these proven agents, dapagliflozin (Farxiga) and empagliflozin (Jardiance), first requires diagnosis of HFpEF, a task that clinicians have historically fallen short in accomplishing.

When in 2021, results from the EMPEROR-Preserved trial with empagliflozin and when in September 2022 results from the DELIVER trial with dapagliflozin established the efficacy of these two SGLT2 inhibitors as the first treatments proven to benefit patients with HFpEF, they also raised the stakes for clinicians to be much more diligent and systematic in evaluating people at high risk for developing HFpEF because of having type 2 diabetes or obesity, two of the most potent risk factors for this form of heart failure.
 

‘Vigilance ... needs to increase’

“Vigilance for HFpEF needs to increase because we can now help these patients,” declared Lars H. Lund, MD, PhD, speaking at the meeting. “Type 2 diabetes dramatically increases the incidence of HFpEF,” and the mechanisms by which it does this are “especially amenable to treatment with SGLT2 inhibitors,” said Dr. Lund, a cardiologist and heart failure specialist at the Karolinska Institute, Stockholm.

HFpEF has a history of going undetected in people with type 2 diabetes, an ironic situation given its high incidence as well as the elevated rate of adverse cardiovascular events when heart failure occurs in patients with type 2 diabetes compared with patients who do not have diabetes.

The key, say experts, is for clinicians to maintain a high index of suspicion for signs and symptoms of heart failure in people with type 2 diabetes and to regularly assess them, starting with just a few simple questions that probe for the presence of dyspnea, exertional fatigue, or both, an approach not widely employed up to now.

Clinicians who care for people with type 2 diabetes must become “alert to thinking about heart failure and alert to asking questions about signs and symptoms” that flag the presence of HFpEF, advised Naveed Sattar, MBChB, PhD, a professor of metabolic medicine at the University of Glasgow.

Soon, medical groups will issue guidelines for appropriate assessment for the presence of HFpEF in people with type 2 diabetes, Dr. Sattar predicted in an interview.
 

A need to probe

“You can’t simply ask patients with type 2 diabetes whether they have shortness of breath or exertional fatigue and stop there,” because often their first response will be no.

“Commonly, patients will initially say they have no dyspnea, but when you probe further, you find symptoms,” noted Mikhail N. Kosiborod, MD, codirector of Saint Luke’s Cardiometabolic Center of Excellence in Kansas City, Mo.

These people are often sedentary, so they frequently don’t experience shortness of breath at baseline, Dr. Kosiborod said in an interview. In some cases, they may limit their activity because of their exertional intolerance.

Once a person’s suggestive symptoms become known, the next step is to measure the serum level of N-terminal pro-B-type natriuretic peptide (NT-proBNP), a biomarker considered to be a generally reliable signal of existing heart failure when elevated.

Any value above 125 pg/mL is suggestive of prevalent heart failure and should lead to the next diagnostic step of echocardiography, Dr. Sattar said.

Elevated NT-proBNP has such good positive predictive value for identifying heart failure that it is tempting to use it broadly in people with type 2 diabetes. A 2022 consensus report from the American Diabetes Association says that “measurement of a natriuretic peptide [such as NT-proBNP] or high-sensitivity cardiac troponin is recommended on at least a yearly basis to identify the earliest HF [heart failure] stages and implement strategies to prevent transition to symptomatic HF.”
 

Test costs require targeting

But because of the relatively high current price for an NT-proBNP test, the cost-benefit ratio for widespread annual testing of all people with type 2 diabetes would be poor, some experts caution.

“Screening everyone may not be the right answer. Hundreds of millions of people worldwide” have type 2 diabetes. “You first need to target evaluation to people with symptoms,” advised Dr. Kosiborod.

He also warned that a low NT-proBNP level does not always rule out HFpEF, especially among people with type 2 diabetes who also have overweight or obesity, because NT-proBNP levels can be “artificially low” in people with obesity.

Other potential aids to diagnosis are assessment scores that researchers have developed, such as the H2FPEF score, which relies on variables that include age, obesity, and the presence of atrial fibrillation and hypertension.

However, this score also requires an echocardiography examination, another test that would have a questionable cost-benefit ratio if performed widely for patients with type 2 diabetes without targeting, Dr. Kosiborod said.
 

SGLT2 inhibitors benefit HFpEF regardless of glucose levels

A prespecified analysis of the DELIVER results that divided the study cohort on the basis of their glycemic status proved the efficacy of the SGLT2 inhibitor dapagliflozin for patients with HFpEF regardless of whether or not they had type 2 diabetes, prediabetes, or were normoglycemic at entry into the study, Silvio E. Inzucchi, MD, reported at the EASD meeting.

Mitchel L. Zoler/MDedge News

Treatment with dapagliflozin cut the incidence of the trial’s primary outcome of cardiovascular death or worsening heart failure by a significant 18% relative to placebo among all enrolled patients.

The new analysis reported by Dr. Inzucchi showed that treatment was associated with a 23% relative risk reduction among those with normoglycemia, a 13% reduction among those with prediabetes, and a 19% reduction among those with type 2 diabetes, with no signal of a significant difference among the three subgroups.

“There was no statistical interaction between categorical glycemic subgrouping and dapagliflozin’s treatment effect,” concluded Dr. Inzucchi, director of the Yale Medicine Diabetes Center, New Haven, Conn.

He also reported that, among the 6,259 people in the trial with HFpEF, 50% had diabetes, 31% had prediabetes, and a scant 19% had normoglycemia. The finding highlights once again the high prevalence of dysglycemia among people with HFpEF.

Previously, a prespecified secondary analysis of data from the EMPEROR-Preserved trial yielded similar findings for empagliflozin that showed the agent’s efficacy for people with HFpEF across the range of glucose levels.

The DELIVER trial was funded by AstraZeneca, the company that markets dapagliflozin (Farxiga). The EMPEROR-Preserved trial was sponsored by Boehringer Ingelheim and Eli Lilly, the companies that jointly market empagliflozin (Jardiance). Dr. Lund has been a consultant to AstraZeneca and Boehringer Ingelheim and to numerous other companies, and he is a stockholder in AnaCardio. Dr. Sattar has been a consultant to and has received research support from AstraZeneca and Boehringer Ingelheim, and he has been a consultant with numerous companies. Dr. Kosiborod has been a consultant to and has received research funding from AstraZeneca and Boehringer Ingelheim and has been a consultant to Eli Lilly and numerous other companies. Dr. Inzucchi has been a consultant to, given talks on behalf of, or served on trial committees for Abbott, AstraZeneca, Boehringer Ingelheim, Esperion, Lexicon, Merck, Novo Nordisk, Pfizer, and vTv Therapetics.

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

STOCKHOLM – Recent study results confirm that two agents from the sodium-glucose cotransporter 2 (SGLT2) inhibitor class can significantly cut the incidence of adverse cardiovascular events in patients with heart failure with reduced ejection fraction (HFpEF), a disease especially common in people with type 2 diabetes, obesity, or both.

And findings from secondary analyses of the studies – including one reported at the annual meeting of the European Association for the Study of Diabetes – show that these SGLT2 inhibitors work as well for cutting incident adverse events (cardiovascular death or worsening heart failure) in patients with HFpEF and diabetes as they do for people with normal blood glucose levels.

But delivering treatment with these proven agents, dapagliflozin (Farxiga) and empagliflozin (Jardiance), first requires diagnosis of HFpEF, a task that clinicians have historically fallen short in accomplishing.

When in 2021, results from the EMPEROR-Preserved trial with empagliflozin and when in September 2022 results from the DELIVER trial with dapagliflozin established the efficacy of these two SGLT2 inhibitors as the first treatments proven to benefit patients with HFpEF, they also raised the stakes for clinicians to be much more diligent and systematic in evaluating people at high risk for developing HFpEF because of having type 2 diabetes or obesity, two of the most potent risk factors for this form of heart failure.
 

‘Vigilance ... needs to increase’

“Vigilance for HFpEF needs to increase because we can now help these patients,” declared Lars H. Lund, MD, PhD, speaking at the meeting. “Type 2 diabetes dramatically increases the incidence of HFpEF,” and the mechanisms by which it does this are “especially amenable to treatment with SGLT2 inhibitors,” said Dr. Lund, a cardiologist and heart failure specialist at the Karolinska Institute, Stockholm.

HFpEF has a history of going undetected in people with type 2 diabetes, an ironic situation given its high incidence as well as the elevated rate of adverse cardiovascular events when heart failure occurs in patients with type 2 diabetes compared with patients who do not have diabetes.

The key, say experts, is for clinicians to maintain a high index of suspicion for signs and symptoms of heart failure in people with type 2 diabetes and to regularly assess them, starting with just a few simple questions that probe for the presence of dyspnea, exertional fatigue, or both, an approach not widely employed up to now.

Clinicians who care for people with type 2 diabetes must become “alert to thinking about heart failure and alert to asking questions about signs and symptoms” that flag the presence of HFpEF, advised Naveed Sattar, MBChB, PhD, a professor of metabolic medicine at the University of Glasgow.

Soon, medical groups will issue guidelines for appropriate assessment for the presence of HFpEF in people with type 2 diabetes, Dr. Sattar predicted in an interview.
 

A need to probe

“You can’t simply ask patients with type 2 diabetes whether they have shortness of breath or exertional fatigue and stop there,” because often their first response will be no.

“Commonly, patients will initially say they have no dyspnea, but when you probe further, you find symptoms,” noted Mikhail N. Kosiborod, MD, codirector of Saint Luke’s Cardiometabolic Center of Excellence in Kansas City, Mo.

These people are often sedentary, so they frequently don’t experience shortness of breath at baseline, Dr. Kosiborod said in an interview. In some cases, they may limit their activity because of their exertional intolerance.

Once a person’s suggestive symptoms become known, the next step is to measure the serum level of N-terminal pro-B-type natriuretic peptide (NT-proBNP), a biomarker considered to be a generally reliable signal of existing heart failure when elevated.

Any value above 125 pg/mL is suggestive of prevalent heart failure and should lead to the next diagnostic step of echocardiography, Dr. Sattar said.

Elevated NT-proBNP has such good positive predictive value for identifying heart failure that it is tempting to use it broadly in people with type 2 diabetes. A 2022 consensus report from the American Diabetes Association says that “measurement of a natriuretic peptide [such as NT-proBNP] or high-sensitivity cardiac troponin is recommended on at least a yearly basis to identify the earliest HF [heart failure] stages and implement strategies to prevent transition to symptomatic HF.”
 

Test costs require targeting

But because of the relatively high current price for an NT-proBNP test, the cost-benefit ratio for widespread annual testing of all people with type 2 diabetes would be poor, some experts caution.

“Screening everyone may not be the right answer. Hundreds of millions of people worldwide” have type 2 diabetes. “You first need to target evaluation to people with symptoms,” advised Dr. Kosiborod.

He also warned that a low NT-proBNP level does not always rule out HFpEF, especially among people with type 2 diabetes who also have overweight or obesity, because NT-proBNP levels can be “artificially low” in people with obesity.

Other potential aids to diagnosis are assessment scores that researchers have developed, such as the H2FPEF score, which relies on variables that include age, obesity, and the presence of atrial fibrillation and hypertension.

However, this score also requires an echocardiography examination, another test that would have a questionable cost-benefit ratio if performed widely for patients with type 2 diabetes without targeting, Dr. Kosiborod said.
 

SGLT2 inhibitors benefit HFpEF regardless of glucose levels

A prespecified analysis of the DELIVER results that divided the study cohort on the basis of their glycemic status proved the efficacy of the SGLT2 inhibitor dapagliflozin for patients with HFpEF regardless of whether or not they had type 2 diabetes, prediabetes, or were normoglycemic at entry into the study, Silvio E. Inzucchi, MD, reported at the EASD meeting.

Mitchel L. Zoler/MDedge News

Treatment with dapagliflozin cut the incidence of the trial’s primary outcome of cardiovascular death or worsening heart failure by a significant 18% relative to placebo among all enrolled patients.

The new analysis reported by Dr. Inzucchi showed that treatment was associated with a 23% relative risk reduction among those with normoglycemia, a 13% reduction among those with prediabetes, and a 19% reduction among those with type 2 diabetes, with no signal of a significant difference among the three subgroups.

“There was no statistical interaction between categorical glycemic subgrouping and dapagliflozin’s treatment effect,” concluded Dr. Inzucchi, director of the Yale Medicine Diabetes Center, New Haven, Conn.

He also reported that, among the 6,259 people in the trial with HFpEF, 50% had diabetes, 31% had prediabetes, and a scant 19% had normoglycemia. The finding highlights once again the high prevalence of dysglycemia among people with HFpEF.

Previously, a prespecified secondary analysis of data from the EMPEROR-Preserved trial yielded similar findings for empagliflozin that showed the agent’s efficacy for people with HFpEF across the range of glucose levels.

The DELIVER trial was funded by AstraZeneca, the company that markets dapagliflozin (Farxiga). The EMPEROR-Preserved trial was sponsored by Boehringer Ingelheim and Eli Lilly, the companies that jointly market empagliflozin (Jardiance). Dr. Lund has been a consultant to AstraZeneca and Boehringer Ingelheim and to numerous other companies, and he is a stockholder in AnaCardio. Dr. Sattar has been a consultant to and has received research support from AstraZeneca and Boehringer Ingelheim, and he has been a consultant with numerous companies. Dr. Kosiborod has been a consultant to and has received research funding from AstraZeneca and Boehringer Ingelheim and has been a consultant to Eli Lilly and numerous other companies. Dr. Inzucchi has been a consultant to, given talks on behalf of, or served on trial committees for Abbott, AstraZeneca, Boehringer Ingelheim, Esperion, Lexicon, Merck, Novo Nordisk, Pfizer, and vTv Therapetics.

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

STOCKHOLM – Recent study results confirm that two agents from the sodium-glucose cotransporter 2 (SGLT2) inhibitor class can significantly cut the incidence of adverse cardiovascular events in patients with heart failure with reduced ejection fraction (HFpEF), a disease especially common in people with type 2 diabetes, obesity, or both.

And findings from secondary analyses of the studies – including one reported at the annual meeting of the European Association for the Study of Diabetes – show that these SGLT2 inhibitors work as well for cutting incident adverse events (cardiovascular death or worsening heart failure) in patients with HFpEF and diabetes as they do for people with normal blood glucose levels.

But delivering treatment with these proven agents, dapagliflozin (Farxiga) and empagliflozin (Jardiance), first requires diagnosis of HFpEF, a task that clinicians have historically fallen short in accomplishing.

When in 2021, results from the EMPEROR-Preserved trial with empagliflozin and when in September 2022 results from the DELIVER trial with dapagliflozin established the efficacy of these two SGLT2 inhibitors as the first treatments proven to benefit patients with HFpEF, they also raised the stakes for clinicians to be much more diligent and systematic in evaluating people at high risk for developing HFpEF because of having type 2 diabetes or obesity, two of the most potent risk factors for this form of heart failure.
 

‘Vigilance ... needs to increase’

“Vigilance for HFpEF needs to increase because we can now help these patients,” declared Lars H. Lund, MD, PhD, speaking at the meeting. “Type 2 diabetes dramatically increases the incidence of HFpEF,” and the mechanisms by which it does this are “especially amenable to treatment with SGLT2 inhibitors,” said Dr. Lund, a cardiologist and heart failure specialist at the Karolinska Institute, Stockholm.

HFpEF has a history of going undetected in people with type 2 diabetes, an ironic situation given its high incidence as well as the elevated rate of adverse cardiovascular events when heart failure occurs in patients with type 2 diabetes compared with patients who do not have diabetes.

The key, say experts, is for clinicians to maintain a high index of suspicion for signs and symptoms of heart failure in people with type 2 diabetes and to regularly assess them, starting with just a few simple questions that probe for the presence of dyspnea, exertional fatigue, or both, an approach not widely employed up to now.

Clinicians who care for people with type 2 diabetes must become “alert to thinking about heart failure and alert to asking questions about signs and symptoms” that flag the presence of HFpEF, advised Naveed Sattar, MBChB, PhD, a professor of metabolic medicine at the University of Glasgow.

Soon, medical groups will issue guidelines for appropriate assessment for the presence of HFpEF in people with type 2 diabetes, Dr. Sattar predicted in an interview.
 

A need to probe

“You can’t simply ask patients with type 2 diabetes whether they have shortness of breath or exertional fatigue and stop there,” because often their first response will be no.

“Commonly, patients will initially say they have no dyspnea, but when you probe further, you find symptoms,” noted Mikhail N. Kosiborod, MD, codirector of Saint Luke’s Cardiometabolic Center of Excellence in Kansas City, Mo.

These people are often sedentary, so they frequently don’t experience shortness of breath at baseline, Dr. Kosiborod said in an interview. In some cases, they may limit their activity because of their exertional intolerance.

Once a person’s suggestive symptoms become known, the next step is to measure the serum level of N-terminal pro-B-type natriuretic peptide (NT-proBNP), a biomarker considered to be a generally reliable signal of existing heart failure when elevated.

Any value above 125 pg/mL is suggestive of prevalent heart failure and should lead to the next diagnostic step of echocardiography, Dr. Sattar said.

Elevated NT-proBNP has such good positive predictive value for identifying heart failure that it is tempting to use it broadly in people with type 2 diabetes. A 2022 consensus report from the American Diabetes Association says that “measurement of a natriuretic peptide [such as NT-proBNP] or high-sensitivity cardiac troponin is recommended on at least a yearly basis to identify the earliest HF [heart failure] stages and implement strategies to prevent transition to symptomatic HF.”
 

Test costs require targeting

But because of the relatively high current price for an NT-proBNP test, the cost-benefit ratio for widespread annual testing of all people with type 2 diabetes would be poor, some experts caution.

“Screening everyone may not be the right answer. Hundreds of millions of people worldwide” have type 2 diabetes. “You first need to target evaluation to people with symptoms,” advised Dr. Kosiborod.

He also warned that a low NT-proBNP level does not always rule out HFpEF, especially among people with type 2 diabetes who also have overweight or obesity, because NT-proBNP levels can be “artificially low” in people with obesity.

Other potential aids to diagnosis are assessment scores that researchers have developed, such as the H2FPEF score, which relies on variables that include age, obesity, and the presence of atrial fibrillation and hypertension.

However, this score also requires an echocardiography examination, another test that would have a questionable cost-benefit ratio if performed widely for patients with type 2 diabetes without targeting, Dr. Kosiborod said.
 

SGLT2 inhibitors benefit HFpEF regardless of glucose levels

A prespecified analysis of the DELIVER results that divided the study cohort on the basis of their glycemic status proved the efficacy of the SGLT2 inhibitor dapagliflozin for patients with HFpEF regardless of whether or not they had type 2 diabetes, prediabetes, or were normoglycemic at entry into the study, Silvio E. Inzucchi, MD, reported at the EASD meeting.

Mitchel L. Zoler/MDedge News

Treatment with dapagliflozin cut the incidence of the trial’s primary outcome of cardiovascular death or worsening heart failure by a significant 18% relative to placebo among all enrolled patients.

The new analysis reported by Dr. Inzucchi showed that treatment was associated with a 23% relative risk reduction among those with normoglycemia, a 13% reduction among those with prediabetes, and a 19% reduction among those with type 2 diabetes, with no signal of a significant difference among the three subgroups.

“There was no statistical interaction between categorical glycemic subgrouping and dapagliflozin’s treatment effect,” concluded Dr. Inzucchi, director of the Yale Medicine Diabetes Center, New Haven, Conn.

He also reported that, among the 6,259 people in the trial with HFpEF, 50% had diabetes, 31% had prediabetes, and a scant 19% had normoglycemia. The finding highlights once again the high prevalence of dysglycemia among people with HFpEF.

Previously, a prespecified secondary analysis of data from the EMPEROR-Preserved trial yielded similar findings for empagliflozin that showed the agent’s efficacy for people with HFpEF across the range of glucose levels.

The DELIVER trial was funded by AstraZeneca, the company that markets dapagliflozin (Farxiga). The EMPEROR-Preserved trial was sponsored by Boehringer Ingelheim and Eli Lilly, the companies that jointly market empagliflozin (Jardiance). Dr. Lund has been a consultant to AstraZeneca and Boehringer Ingelheim and to numerous other companies, and he is a stockholder in AnaCardio. Dr. Sattar has been a consultant to and has received research support from AstraZeneca and Boehringer Ingelheim, and he has been a consultant with numerous companies. Dr. Kosiborod has been a consultant to and has received research funding from AstraZeneca and Boehringer Ingelheim and has been a consultant to Eli Lilly and numerous other companies. Dr. Inzucchi has been a consultant to, given talks on behalf of, or served on trial committees for Abbott, AstraZeneca, Boehringer Ingelheim, Esperion, Lexicon, Merck, Novo Nordisk, Pfizer, and vTv Therapetics.

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

Spironolactone, a potassium-sparing diuretic typically used to treat heart failure and hypertension, shows promise in treating alcohol use disorder (AUD), new research suggests.

Researchers at the National Institute on Drug Abuse, the National Institute on Alcohol Abuse and Alcoholism, and Yale University, New Haven, Conn., investigated the impact of spironolactone on AUD.

Initially, they studied rodents and found that spironolactone reduced binge drinking in mice and reduced self-administration of alcohol in rats without adversely affecting food or water intake or causing motor or coordination problems.

They also analyzed electronic health records of patients drawn from the United States Veterans Affairs health care system to explore potential changes in alcohol use after spironolactone treatment was initiated for other conditions and found a significant link between spironolactone treatment and reduction in self-reported alcohol consumption, with the largest effects observed among those who reported hazardous/heavy episodic alcohol use prior to starting spironolactone treatment.

“Combining findings across three species and different types of research studies, and then seeing similarities in these data, gives us confidence that we are onto something potentially important scientifically and clinically,” senior coauthor Lorenzo Leggio, MD, PhD, senior investigator in the Clinical Psychoneuroendocrinology and Neuropsychopharmacology Section, a joint NIDA and NIAAA laboratory, said in a news release.

The study was published online in Molecular Psychiatry.
 

There is a “critical need to increase the armamentarium of pharmacotherapies to treat individuals with AUD,” the authors note, adding that neuroendocrine systems involved in alcohol craving and drinking “offer promising pharmacologic targets in this regard.”

“Both our team and others have observed that patients with AUD often present with changes in peripheral hormones, including aldosterone, which plays a key role in regulating blood pressure and electrolytes,” Dr. Leggio said in an interview.

Spironolactone is a nonselective mineralocorticoid receptor (MT) antagonist. In studies in animal models, investigators said they found “an inverse correlation between alcohol drinking and the expression of the MR in the amygdala, a key brain region in the development and maintenance of AUD and addiction in general.”

Taken together, this led them to hypothesize that blocking the MR, which is the mechanism of action of spironolactone, “could be a novel pharmacotherapeutic approach for AUD,” he said.

Previous research by the same group of researchers suggested spironolactone “may be a potential new medication to treat patients with AUD.” The present study expanded on those findings and consisted of a three-part investigation.

In the current study, the investigators tested different dosages of spironolactone on binge-like alcohol consumption in male and female mice and assessed food and water intake, blood alcohol levels, motor coordination, and spontaneous locomotion.

They then tested the effects of different dosages of spironolactone injections on operant alcohol self-administration in alcohol-dependent and nondependent male and female rats, also testing blood alcohol levels and motor coordination.

Finally, they analyzed health records of veterans to examine the association between at least 60 continuous days of spironolactone treatment and self-reported alcohol consumption (measured by the Alcohol Use Disorders Identification Test-Consumption [AUDIT-C]).

Each of the spironolactone-exposed patients was matched using propensity scores with up to five unexposed patients who had reported alcohol consumption in the 2 years prior to the index date.

The final analysis included a matched cohort of 10,726 spironolactone-exposed individuals who were matched to 34,461 unexposed individuals.
 

New targets

Spironolactone reduced alcohol intake in mice drinking a sweetened alcohol solution; a 2-way ANOVA revealed a main effect of dose (F 4,52 = 9.09; P < .0001) and sex, with female mice drinking more alcohol, compared to male mice (F 1,13 = 6.05; P = .02).

Post hoc comparisons showed that spironolactone at doses of 50, 100, and 200 mg/kg significantly reduced alcohol intake (P values = .007, .002, and .0001, respectively).

In mice drinking an unsweetened alcohol solution, the 2-way repeated measures ANOVA similarly found a main effect of dose (F 4,52 = 5.77; P = .0006), but not of sex (F 1,13 = 1.41; P = .25).

Spironolactone had no effect on the mice’s intake of a sweet solution without alcohol and had no impact on the consumption of food and water or on locomotion and coordination.

In rats, a 2-way ANOVA revealed a significant spironolactone effect of dose (F 3,66 = 43.95; P < .001), with a post hoc test indicating that spironolactone at 25, 50, and 75 mg/kg reduced alcohol self-administration in alcohol-dependent and nondependent rats (all P values = .0001).

In humans, among the exposed individuals in the matched cohort, 25%, 57%, and 18% received daily doses of spironolactone of less than 25 mg/day, 25-49 mg/day, and 50 mg/day or higher, respectively, with a median follow-up time of 542 (interquartile range, 337-730) days.

The AUDIT-C scores decreased during the study period in both treatment groups, with a larger decrease in average AUDIT-C scores among the exposed vs. unexposed individuals.

“These are very exciting times because, thanks to the progress in the addiction biomedical research field, we are increasing our understanding of the mechanisms how some people develop AUD; hence we can use this knowledge to identify new targets.” The current study “is an example of these ongoing efforts,” said Dr. Leggio.

“It is important to note that [these results] are important but preliminary.” At this juncture, “it would be too premature to think about prescribing spironolactone to treat AUD,” he added.

 

Exciting findings

Commenting on the study, Joyce Besheer, PhD, professor, department of psychiatry and Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, called the study an “elegant demonstration of translational science.”

“While clinical trials will be needed to determine whether this medication is effective at reducing drinking in patients with AUD, these findings are exciting as they suggest that spironolactone may be a promising compound and new treatment options for AUD are much needed,” said Dr. Besheer, who was not involved with the current study.

Dr. Leggio agreed. “We now need prospective, placebo-controlled studies to assess the potential safety and efficacy of spironolactone in people with AUD,” he said.

This work was supported by the National Institutes of Health and the NIAAA. Dr. Leggio, study coauthors, and Dr. Besheer declare no relevant financial relationships.

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

Spironolactone, a potassium-sparing diuretic typically used to treat heart failure and hypertension, shows promise in treating alcohol use disorder (AUD), new research suggests.

Researchers at the National Institute on Drug Abuse, the National Institute on Alcohol Abuse and Alcoholism, and Yale University, New Haven, Conn., investigated the impact of spironolactone on AUD.

Initially, they studied rodents and found that spironolactone reduced binge drinking in mice and reduced self-administration of alcohol in rats without adversely affecting food or water intake or causing motor or coordination problems.

They also analyzed electronic health records of patients drawn from the United States Veterans Affairs health care system to explore potential changes in alcohol use after spironolactone treatment was initiated for other conditions and found a significant link between spironolactone treatment and reduction in self-reported alcohol consumption, with the largest effects observed among those who reported hazardous/heavy episodic alcohol use prior to starting spironolactone treatment.

“Combining findings across three species and different types of research studies, and then seeing similarities in these data, gives us confidence that we are onto something potentially important scientifically and clinically,” senior coauthor Lorenzo Leggio, MD, PhD, senior investigator in the Clinical Psychoneuroendocrinology and Neuropsychopharmacology Section, a joint NIDA and NIAAA laboratory, said in a news release.

The study was published online in Molecular Psychiatry.
 

There is a “critical need to increase the armamentarium of pharmacotherapies to treat individuals with AUD,” the authors note, adding that neuroendocrine systems involved in alcohol craving and drinking “offer promising pharmacologic targets in this regard.”

“Both our team and others have observed that patients with AUD often present with changes in peripheral hormones, including aldosterone, which plays a key role in regulating blood pressure and electrolytes,” Dr. Leggio said in an interview.

Spironolactone is a nonselective mineralocorticoid receptor (MT) antagonist. In studies in animal models, investigators said they found “an inverse correlation between alcohol drinking and the expression of the MR in the amygdala, a key brain region in the development and maintenance of AUD and addiction in general.”

Taken together, this led them to hypothesize that blocking the MR, which is the mechanism of action of spironolactone, “could be a novel pharmacotherapeutic approach for AUD,” he said.

Previous research by the same group of researchers suggested spironolactone “may be a potential new medication to treat patients with AUD.” The present study expanded on those findings and consisted of a three-part investigation.

In the current study, the investigators tested different dosages of spironolactone on binge-like alcohol consumption in male and female mice and assessed food and water intake, blood alcohol levels, motor coordination, and spontaneous locomotion.

They then tested the effects of different dosages of spironolactone injections on operant alcohol self-administration in alcohol-dependent and nondependent male and female rats, also testing blood alcohol levels and motor coordination.

Finally, they analyzed health records of veterans to examine the association between at least 60 continuous days of spironolactone treatment and self-reported alcohol consumption (measured by the Alcohol Use Disorders Identification Test-Consumption [AUDIT-C]).

Each of the spironolactone-exposed patients was matched using propensity scores with up to five unexposed patients who had reported alcohol consumption in the 2 years prior to the index date.

The final analysis included a matched cohort of 10,726 spironolactone-exposed individuals who were matched to 34,461 unexposed individuals.
 

New targets

Spironolactone reduced alcohol intake in mice drinking a sweetened alcohol solution; a 2-way ANOVA revealed a main effect of dose (F 4,52 = 9.09; P < .0001) and sex, with female mice drinking more alcohol, compared to male mice (F 1,13 = 6.05; P = .02).

Post hoc comparisons showed that spironolactone at doses of 50, 100, and 200 mg/kg significantly reduced alcohol intake (P values = .007, .002, and .0001, respectively).

In mice drinking an unsweetened alcohol solution, the 2-way repeated measures ANOVA similarly found a main effect of dose (F 4,52 = 5.77; P = .0006), but not of sex (F 1,13 = 1.41; P = .25).

Spironolactone had no effect on the mice’s intake of a sweet solution without alcohol and had no impact on the consumption of food and water or on locomotion and coordination.

In rats, a 2-way ANOVA revealed a significant spironolactone effect of dose (F 3,66 = 43.95; P < .001), with a post hoc test indicating that spironolactone at 25, 50, and 75 mg/kg reduced alcohol self-administration in alcohol-dependent and nondependent rats (all P values = .0001).

In humans, among the exposed individuals in the matched cohort, 25%, 57%, and 18% received daily doses of spironolactone of less than 25 mg/day, 25-49 mg/day, and 50 mg/day or higher, respectively, with a median follow-up time of 542 (interquartile range, 337-730) days.

The AUDIT-C scores decreased during the study period in both treatment groups, with a larger decrease in average AUDIT-C scores among the exposed vs. unexposed individuals.

“These are very exciting times because, thanks to the progress in the addiction biomedical research field, we are increasing our understanding of the mechanisms how some people develop AUD; hence we can use this knowledge to identify new targets.” The current study “is an example of these ongoing efforts,” said Dr. Leggio.

“It is important to note that [these results] are important but preliminary.” At this juncture, “it would be too premature to think about prescribing spironolactone to treat AUD,” he added.

 

Exciting findings

Commenting on the study, Joyce Besheer, PhD, professor, department of psychiatry and Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, called the study an “elegant demonstration of translational science.”

“While clinical trials will be needed to determine whether this medication is effective at reducing drinking in patients with AUD, these findings are exciting as they suggest that spironolactone may be a promising compound and new treatment options for AUD are much needed,” said Dr. Besheer, who was not involved with the current study.

Dr. Leggio agreed. “We now need prospective, placebo-controlled studies to assess the potential safety and efficacy of spironolactone in people with AUD,” he said.

This work was supported by the National Institutes of Health and the NIAAA. Dr. Leggio, study coauthors, and Dr. Besheer declare no relevant financial relationships.

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

Spironolactone, a potassium-sparing diuretic typically used to treat heart failure and hypertension, shows promise in treating alcohol use disorder (AUD), new research suggests.

Researchers at the National Institute on Drug Abuse, the National Institute on Alcohol Abuse and Alcoholism, and Yale University, New Haven, Conn., investigated the impact of spironolactone on AUD.

Initially, they studied rodents and found that spironolactone reduced binge drinking in mice and reduced self-administration of alcohol in rats without adversely affecting food or water intake or causing motor or coordination problems.

They also analyzed electronic health records of patients drawn from the United States Veterans Affairs health care system to explore potential changes in alcohol use after spironolactone treatment was initiated for other conditions and found a significant link between spironolactone treatment and reduction in self-reported alcohol consumption, with the largest effects observed among those who reported hazardous/heavy episodic alcohol use prior to starting spironolactone treatment.

“Combining findings across three species and different types of research studies, and then seeing similarities in these data, gives us confidence that we are onto something potentially important scientifically and clinically,” senior coauthor Lorenzo Leggio, MD, PhD, senior investigator in the Clinical Psychoneuroendocrinology and Neuropsychopharmacology Section, a joint NIDA and NIAAA laboratory, said in a news release.

The study was published online in Molecular Psychiatry.
 

There is a “critical need to increase the armamentarium of pharmacotherapies to treat individuals with AUD,” the authors note, adding that neuroendocrine systems involved in alcohol craving and drinking “offer promising pharmacologic targets in this regard.”

“Both our team and others have observed that patients with AUD often present with changes in peripheral hormones, including aldosterone, which plays a key role in regulating blood pressure and electrolytes,” Dr. Leggio said in an interview.

Spironolactone is a nonselective mineralocorticoid receptor (MT) antagonist. In studies in animal models, investigators said they found “an inverse correlation between alcohol drinking and the expression of the MR in the amygdala, a key brain region in the development and maintenance of AUD and addiction in general.”

Taken together, this led them to hypothesize that blocking the MR, which is the mechanism of action of spironolactone, “could be a novel pharmacotherapeutic approach for AUD,” he said.

Previous research by the same group of researchers suggested spironolactone “may be a potential new medication to treat patients with AUD.” The present study expanded on those findings and consisted of a three-part investigation.

In the current study, the investigators tested different dosages of spironolactone on binge-like alcohol consumption in male and female mice and assessed food and water intake, blood alcohol levels, motor coordination, and spontaneous locomotion.

They then tested the effects of different dosages of spironolactone injections on operant alcohol self-administration in alcohol-dependent and nondependent male and female rats, also testing blood alcohol levels and motor coordination.

Finally, they analyzed health records of veterans to examine the association between at least 60 continuous days of spironolactone treatment and self-reported alcohol consumption (measured by the Alcohol Use Disorders Identification Test-Consumption [AUDIT-C]).

Each of the spironolactone-exposed patients was matched using propensity scores with up to five unexposed patients who had reported alcohol consumption in the 2 years prior to the index date.

The final analysis included a matched cohort of 10,726 spironolactone-exposed individuals who were matched to 34,461 unexposed individuals.
 

New targets

Spironolactone reduced alcohol intake in mice drinking a sweetened alcohol solution; a 2-way ANOVA revealed a main effect of dose (F 4,52 = 9.09; P < .0001) and sex, with female mice drinking more alcohol, compared to male mice (F 1,13 = 6.05; P = .02).

Post hoc comparisons showed that spironolactone at doses of 50, 100, and 200 mg/kg significantly reduced alcohol intake (P values = .007, .002, and .0001, respectively).

In mice drinking an unsweetened alcohol solution, the 2-way repeated measures ANOVA similarly found a main effect of dose (F 4,52 = 5.77; P = .0006), but not of sex (F 1,13 = 1.41; P = .25).

Spironolactone had no effect on the mice’s intake of a sweet solution without alcohol and had no impact on the consumption of food and water or on locomotion and coordination.

In rats, a 2-way ANOVA revealed a significant spironolactone effect of dose (F 3,66 = 43.95; P < .001), with a post hoc test indicating that spironolactone at 25, 50, and 75 mg/kg reduced alcohol self-administration in alcohol-dependent and nondependent rats (all P values = .0001).

In humans, among the exposed individuals in the matched cohort, 25%, 57%, and 18% received daily doses of spironolactone of less than 25 mg/day, 25-49 mg/day, and 50 mg/day or higher, respectively, with a median follow-up time of 542 (interquartile range, 337-730) days.

The AUDIT-C scores decreased during the study period in both treatment groups, with a larger decrease in average AUDIT-C scores among the exposed vs. unexposed individuals.

“These are very exciting times because, thanks to the progress in the addiction biomedical research field, we are increasing our understanding of the mechanisms how some people develop AUD; hence we can use this knowledge to identify new targets.” The current study “is an example of these ongoing efforts,” said Dr. Leggio.

“It is important to note that [these results] are important but preliminary.” At this juncture, “it would be too premature to think about prescribing spironolactone to treat AUD,” he added.

 

Exciting findings

Commenting on the study, Joyce Besheer, PhD, professor, department of psychiatry and Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, called the study an “elegant demonstration of translational science.”

“While clinical trials will be needed to determine whether this medication is effective at reducing drinking in patients with AUD, these findings are exciting as they suggest that spironolactone may be a promising compound and new treatment options for AUD are much needed,” said Dr. Besheer, who was not involved with the current study.

Dr. Leggio agreed. “We now need prospective, placebo-controlled studies to assess the potential safety and efficacy of spironolactone in people with AUD,” he said.

This work was supported by the National Institutes of Health and the NIAAA. Dr. Leggio, study coauthors, and Dr. Besheer declare no relevant financial relationships.

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