Cardiology News

Chronic conditions like diabetes or hypertension “often require long-term care through long-term monitoring,” observed a researcher, and “we know that continuous monitoring is superior to intermittent monitoring for long-term outcomes.”

So maybe practice should rely more on continuous ECG monitoring for patients with atrial fibrillation (AFib), also a chronic condition, proposed Dhanunjaya R. Lakkireddy, MD, of the Kansas City Heart Rhythm Institute, Overland Park, Kan., in presenting a new analysis at the annual scientific sessions of the Heart Rhythm Society.

The observational study with more than 2,400 such patients showed tighter AFib management, greater drug therapy compliance, and better clinical outcomes when clinical decisions were guided by continuous data from implantable loop recorders (ILRs), compared with standard care. The latter could include intermittent 12-lead ECG, Holter, or other intermittent monitoring at physicians’ discretion.

Patients with AFib and the ECG implants in the MONITOR-AF study, which was not randomized and therefore only suggestive, were managed “more efficiently” with greater access to electrophysiologists (P < .01) and adherence to oral anticoagulants (P = .020) and other medications.

Followed for a mean of 2 years, patients with ILRs were more likely to undergo catheter ablation, and their time to a catheter ablation “was impressively shorter, 153 days versus 426 days” (P < .001), Dr. Lakkireddy said.

The ILR group also had fewer strokes and bleeding complications and were less likely to be hospitalized for AFib-related reasons, he said, because “a lot of these patients were caught ahead of time through the remote monitoring.”

For example, ILR patients had fewer heart failure (HF) hospitalizations, likely because “you’re not allowing these patients to remain with untreated rapid ventricular rates for a long period of time. You intervene early, thereby mitigating the onset of heart failure.”

Indeed, Dr. Lakkireddy said, their cumulative rate of any cardiovascular complication was “dramatically lower” – 3.4 versus 10.4 events per 100 person-years (P < .001).

Certainly, a routine recommendation to consider AFib patients for continuous monitoring would require randomized-trial evidence, he acknowledged. “This is an observation registry and proof of concept from a very heterogeneous cohort of patients. There were no obvious set criteria for ILR implantation.”

Nonetheless, “continuous and dynamic monitoring enabled quicker decision-making and patient management,” Dr. Lakkireddy said. “Especially in those patients who may have silent atrial fibrillation, an ILR could significantly mitigate the risk of complications from stroke and heart failure exacerbations.”

Several randomized trials have supported “earlier, more aggressive treatment” for AFib, including EAST-AFNET4, EARLY-AF, and CABANA, observed Daniel Morin, MD, MPH, of Ochsner Medical Center, New Orleans, as the invited discussant for Dr. Lakkireddy’s presentation.

So, he continued, if the goal is to “get every single AFib patient to ablation just as soon as possible,” then maybe MONITOR-AF supports the use of ILRs in such cases.

Indeed, it is “certainly possible” that the continuous stream of data from ILRs “allows faster progression of therapy and possibly even better outcomes” as MONITOR-AF suggests, said Dr. Morin, who is director of electrophysiology research at his center.

Moreover, ILR data could potentially “support shared decision-making perhaps by convincing the patient, and maybe their insurers, that we should move forward with ablation.”

But given the study’s observational, registry-based nature, the MONITOR-AF analysis is limited by potential confounders that complicate its interpretation.

For example, Dr. Morin continued, all ILR patients but only 60% of those on standard care˙ had access to an electrophysiologist (P = .001). That means “less access to some antiarrhythmic medications and certainly far less access to ablation therapy.”

Moreover, “during shared decision-making, a patient who sees the results of their ILR monitoring may be more prone to seek out or to accept earlier, more definitive therapy via ablation,” he said. “The presence of an ILR may then be a good way to move the needle toward ablation.”

Of note, an overwhelming majority of ILR patients received ablation, 93.5%, compared with 58.6% of standard-care patients. “It’s unclear how much of that association was caused by the ILR’s presence vs. other factors, such as physician availability, physician aggressiveness, or patient willingness for intervention,” Dr. Morin noted.

MONITOR-AF included 2,458 patients with paroxysmal or persistent AFib who either were implanted with or did not receive an ILR from 2018 to 2021 and were followed for at least 12 months.

The two groups were similar, Dr. Lakkireddy reported, with respect to demographics and baseline history AFib, hypertension, hyperlipidemia, diabetes, coronary disease, neurovascular events, peripheral artery disease, and obstructive sleep apnea.

Dr. Lakkireddy said a subgroup analysis is forthcoming, but that he’d “intuitively” think that the 15%-20% of AFib patients who are asymptomatic would gain the most from the ILR monitoring approach. There is already evidence that such patients tend to have the worst AFib outcomes, often receiving an AFib diagnosis only after presenting with consequences such as stroke or heart failure.

Dr. Lakkireddy disclosed receiving research grants, modest honoraria, or consulting fees from Abbott, Janssen, Boston Scientific, Johnson & Johnson, Biotronik, Bristol-Myers Squibb, Pfizer, Atricure, Northeast Scientific, and Acutus. Dr. Morin disclosed receiving research grants, honoraria, or consulting fees from Abbott and serving on a speakers’ bureau for Boston Scientific, Medtronic, and Zoll Medical.

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

Chronic conditions like diabetes or hypertension “often require long-term care through long-term monitoring,” observed a researcher, and “we know that continuous monitoring is superior to intermittent monitoring for long-term outcomes.”

So maybe practice should rely more on continuous ECG monitoring for patients with atrial fibrillation (AFib), also a chronic condition, proposed Dhanunjaya R. Lakkireddy, MD, of the Kansas City Heart Rhythm Institute, Overland Park, Kan., in presenting a new analysis at the annual scientific sessions of the Heart Rhythm Society.

The observational study with more than 2,400 such patients showed tighter AFib management, greater drug therapy compliance, and better clinical outcomes when clinical decisions were guided by continuous data from implantable loop recorders (ILRs), compared with standard care. The latter could include intermittent 12-lead ECG, Holter, or other intermittent monitoring at physicians’ discretion.

Patients with AFib and the ECG implants in the MONITOR-AF study, which was not randomized and therefore only suggestive, were managed “more efficiently” with greater access to electrophysiologists (P < .01) and adherence to oral anticoagulants (P = .020) and other medications.

Followed for a mean of 2 years, patients with ILRs were more likely to undergo catheter ablation, and their time to a catheter ablation “was impressively shorter, 153 days versus 426 days” (P < .001), Dr. Lakkireddy said.

The ILR group also had fewer strokes and bleeding complications and were less likely to be hospitalized for AFib-related reasons, he said, because “a lot of these patients were caught ahead of time through the remote monitoring.”

For example, ILR patients had fewer heart failure (HF) hospitalizations, likely because “you’re not allowing these patients to remain with untreated rapid ventricular rates for a long period of time. You intervene early, thereby mitigating the onset of heart failure.”

Indeed, Dr. Lakkireddy said, their cumulative rate of any cardiovascular complication was “dramatically lower” – 3.4 versus 10.4 events per 100 person-years (P < .001).

Certainly, a routine recommendation to consider AFib patients for continuous monitoring would require randomized-trial evidence, he acknowledged. “This is an observation registry and proof of concept from a very heterogeneous cohort of patients. There were no obvious set criteria for ILR implantation.”

Nonetheless, “continuous and dynamic monitoring enabled quicker decision-making and patient management,” Dr. Lakkireddy said. “Especially in those patients who may have silent atrial fibrillation, an ILR could significantly mitigate the risk of complications from stroke and heart failure exacerbations.”

Several randomized trials have supported “earlier, more aggressive treatment” for AFib, including EAST-AFNET4, EARLY-AF, and CABANA, observed Daniel Morin, MD, MPH, of Ochsner Medical Center, New Orleans, as the invited discussant for Dr. Lakkireddy’s presentation.

So, he continued, if the goal is to “get every single AFib patient to ablation just as soon as possible,” then maybe MONITOR-AF supports the use of ILRs in such cases.

Indeed, it is “certainly possible” that the continuous stream of data from ILRs “allows faster progression of therapy and possibly even better outcomes” as MONITOR-AF suggests, said Dr. Morin, who is director of electrophysiology research at his center.

Moreover, ILR data could potentially “support shared decision-making perhaps by convincing the patient, and maybe their insurers, that we should move forward with ablation.”

But given the study’s observational, registry-based nature, the MONITOR-AF analysis is limited by potential confounders that complicate its interpretation.

For example, Dr. Morin continued, all ILR patients but only 60% of those on standard care˙ had access to an electrophysiologist (P = .001). That means “less access to some antiarrhythmic medications and certainly far less access to ablation therapy.”

Moreover, “during shared decision-making, a patient who sees the results of their ILR monitoring may be more prone to seek out or to accept earlier, more definitive therapy via ablation,” he said. “The presence of an ILR may then be a good way to move the needle toward ablation.”

Of note, an overwhelming majority of ILR patients received ablation, 93.5%, compared with 58.6% of standard-care patients. “It’s unclear how much of that association was caused by the ILR’s presence vs. other factors, such as physician availability, physician aggressiveness, or patient willingness for intervention,” Dr. Morin noted.

MONITOR-AF included 2,458 patients with paroxysmal or persistent AFib who either were implanted with or did not receive an ILR from 2018 to 2021 and were followed for at least 12 months.

The two groups were similar, Dr. Lakkireddy reported, with respect to demographics and baseline history AFib, hypertension, hyperlipidemia, diabetes, coronary disease, neurovascular events, peripheral artery disease, and obstructive sleep apnea.

Dr. Lakkireddy said a subgroup analysis is forthcoming, but that he’d “intuitively” think that the 15%-20% of AFib patients who are asymptomatic would gain the most from the ILR monitoring approach. There is already evidence that such patients tend to have the worst AFib outcomes, often receiving an AFib diagnosis only after presenting with consequences such as stroke or heart failure.

Dr. Lakkireddy disclosed receiving research grants, modest honoraria, or consulting fees from Abbott, Janssen, Boston Scientific, Johnson & Johnson, Biotronik, Bristol-Myers Squibb, Pfizer, Atricure, Northeast Scientific, and Acutus. Dr. Morin disclosed receiving research grants, honoraria, or consulting fees from Abbott and serving on a speakers’ bureau for Boston Scientific, Medtronic, and Zoll Medical.

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

Chronic conditions like diabetes or hypertension “often require long-term care through long-term monitoring,” observed a researcher, and “we know that continuous monitoring is superior to intermittent monitoring for long-term outcomes.”

So maybe practice should rely more on continuous ECG monitoring for patients with atrial fibrillation (AFib), also a chronic condition, proposed Dhanunjaya R. Lakkireddy, MD, of the Kansas City Heart Rhythm Institute, Overland Park, Kan., in presenting a new analysis at the annual scientific sessions of the Heart Rhythm Society.

The observational study with more than 2,400 such patients showed tighter AFib management, greater drug therapy compliance, and better clinical outcomes when clinical decisions were guided by continuous data from implantable loop recorders (ILRs), compared with standard care. The latter could include intermittent 12-lead ECG, Holter, or other intermittent monitoring at physicians’ discretion.

Patients with AFib and the ECG implants in the MONITOR-AF study, which was not randomized and therefore only suggestive, were managed “more efficiently” with greater access to electrophysiologists (P < .01) and adherence to oral anticoagulants (P = .020) and other medications.

Followed for a mean of 2 years, patients with ILRs were more likely to undergo catheter ablation, and their time to a catheter ablation “was impressively shorter, 153 days versus 426 days” (P < .001), Dr. Lakkireddy said.

The ILR group also had fewer strokes and bleeding complications and were less likely to be hospitalized for AFib-related reasons, he said, because “a lot of these patients were caught ahead of time through the remote monitoring.”

For example, ILR patients had fewer heart failure (HF) hospitalizations, likely because “you’re not allowing these patients to remain with untreated rapid ventricular rates for a long period of time. You intervene early, thereby mitigating the onset of heart failure.”

Indeed, Dr. Lakkireddy said, their cumulative rate of any cardiovascular complication was “dramatically lower” – 3.4 versus 10.4 events per 100 person-years (P < .001).

Certainly, a routine recommendation to consider AFib patients for continuous monitoring would require randomized-trial evidence, he acknowledged. “This is an observation registry and proof of concept from a very heterogeneous cohort of patients. There were no obvious set criteria for ILR implantation.”

Nonetheless, “continuous and dynamic monitoring enabled quicker decision-making and patient management,” Dr. Lakkireddy said. “Especially in those patients who may have silent atrial fibrillation, an ILR could significantly mitigate the risk of complications from stroke and heart failure exacerbations.”

Several randomized trials have supported “earlier, more aggressive treatment” for AFib, including EAST-AFNET4, EARLY-AF, and CABANA, observed Daniel Morin, MD, MPH, of Ochsner Medical Center, New Orleans, as the invited discussant for Dr. Lakkireddy’s presentation.

So, he continued, if the goal is to “get every single AFib patient to ablation just as soon as possible,” then maybe MONITOR-AF supports the use of ILRs in such cases.

Indeed, it is “certainly possible” that the continuous stream of data from ILRs “allows faster progression of therapy and possibly even better outcomes” as MONITOR-AF suggests, said Dr. Morin, who is director of electrophysiology research at his center.

Moreover, ILR data could potentially “support shared decision-making perhaps by convincing the patient, and maybe their insurers, that we should move forward with ablation.”

But given the study’s observational, registry-based nature, the MONITOR-AF analysis is limited by potential confounders that complicate its interpretation.

For example, Dr. Morin continued, all ILR patients but only 60% of those on standard care˙ had access to an electrophysiologist (P = .001). That means “less access to some antiarrhythmic medications and certainly far less access to ablation therapy.”

Moreover, “during shared decision-making, a patient who sees the results of their ILR monitoring may be more prone to seek out or to accept earlier, more definitive therapy via ablation,” he said. “The presence of an ILR may then be a good way to move the needle toward ablation.”

Of note, an overwhelming majority of ILR patients received ablation, 93.5%, compared with 58.6% of standard-care patients. “It’s unclear how much of that association was caused by the ILR’s presence vs. other factors, such as physician availability, physician aggressiveness, or patient willingness for intervention,” Dr. Morin noted.

MONITOR-AF included 2,458 patients with paroxysmal or persistent AFib who either were implanted with or did not receive an ILR from 2018 to 2021 and were followed for at least 12 months.

The two groups were similar, Dr. Lakkireddy reported, with respect to demographics and baseline history AFib, hypertension, hyperlipidemia, diabetes, coronary disease, neurovascular events, peripheral artery disease, and obstructive sleep apnea.

Dr. Lakkireddy said a subgroup analysis is forthcoming, but that he’d “intuitively” think that the 15%-20% of AFib patients who are asymptomatic would gain the most from the ILR monitoring approach. There is already evidence that such patients tend to have the worst AFib outcomes, often receiving an AFib diagnosis only after presenting with consequences such as stroke or heart failure.

Dr. Lakkireddy disclosed receiving research grants, modest honoraria, or consulting fees from Abbott, Janssen, Boston Scientific, Johnson & Johnson, Biotronik, Bristol-Myers Squibb, Pfizer, Atricure, Northeast Scientific, and Acutus. Dr. Morin disclosed receiving research grants, honoraria, or consulting fees from Abbott and serving on a speakers’ bureau for Boston Scientific, Medtronic, and Zoll Medical.

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

Even the plague wanted to visit Stonehenge

We’re about to blow your mind: The history you learned in school was often inaccurate. Shocking, we know, so we’ll give you a minute to process this incredible news.

Better? Good. Now, let’s look back at high school European history. The Black Death, specifically. The common narrative is that the Mongols, while besieging a Crimean city belonging to the Genoese, catapulted dead bodies infected with some mystery disease that turned out to be the plague. The Genoese then brought the plague back to Italy, and from there, we all know the rest of the story.

Ian Hodkinson, [email protected]

The Black Death was certainly extremely important to the development of modern Europe as we know it, but the history books gloss over the much longer history of the plague. Yersinia pestis did not suddenly appear unbidden in a Mongol war camp in 1347. The Black Death wasn’t even the first horrific, continent-wide pandemic caused by the plague; the Plague of Justinian 800 years earlier crippled the Byzantine Empire during an expansionist phase and killed anywhere between 15 million and 100 million.

Today, though, LOTME looks even deeper into history, nearly beyond even history itself, back into the depths of early Bronze Age northern Europe. Specifically, to two ancient burial sites in England, where researchers have identified three 4,000-year-old cases of Y. pestis, the first recorded incidence of the disease in Britain.

Two of the individuals, identified through analysis of dental pulp, were young children buried at a mass grave in Somerset, while the third, a middle-aged woman, was found in a ring cairn in Cumbria. These sites are hundreds of miles apart, yet carbon dating suggests all three people lived and died at roughly the same time. The strain found is very similar to other samples of plague found across central and western Europe starting around 3,000 BCE, suggesting a single, easily spread disease affecting a large area in a relatively small period of time. In other words, a pandemic. Even in these ancient times, the world was connected. Not even the island of Britain could escape.

Beyond that though, the research helps confirm the cyclical nature of the plague; over time, it loses its effectiveness and goes into hiding, only to mutate and come roaring back. This is a story with absolutely no relevance at all to the modern world. Nope, no plagues or pandemics going around right now, no viruses fading into the background in any way. What a ridiculous inference to make.
 

Uncovering the invisible with artificial intelligence

This week in “What Else Can AI Do?” new research shows that a computer program can reveal brain injury that couldn’t be seen before with typical MRI.

The hot new AI, birthed by researchers at New York University, could potentially be a game changer by linking repeated head impacts with tiny, structural changes in the brains of athletes who have not been diagnosed with a concussion. By using machine learning to train the AI, the researchers were, for the first time, able to distinguish the brain of athletes who played contact sports (football, soccer, lacrosse) from those participating in noncontact sports such as baseball, basketball, and cross-country.

Andrea Danti/Thinkstock

How did they do it? The investigators “designed statistical techniques that gave their computer program the ability to ‘learn’ how to predict exposure to repeated head impacts using mathematical models,” they explained in a written statement. Adding in data from the MRI scans of 81 male athletes with no known concussion diagnosis and the ability to identify unusual brain features between athletes with and without head trauma allowed the AI to predict results with accuracy even Miss Cleo would envy.

“This method may provide an important diagnostic tool not only for concussion, but also for detecting the damage that stems from subtler and more frequent head impacts,” said lead author Junbo Chen, an engineering doctoral candidate at NYU. That could make this new AI a valuable asset to science and medicine.

There are many things the human brain can do that AI can’t, and delegation could be one of them. Examining the data that represent the human brain in minute detail? Maybe we leave that to the machine.
 

Talk about your field promotions

If you’re a surgeon doing an amputation, the list of possible assistants pretty much starts and ends in only one place: Not the closest available janitor.

That may seem like an oddly obvious thing for us to say, but there’s at least one former Mainz (Germany) University Hospital physician who really needed to get this bit of advice before he attempted an unassisted toe amputation back in October of 2020. Yes, that does seem like kind of a long time ago for us to be reporting it now, but the details of the incident only just came to light a few days ago, thanks to German public broadcaster SWR.

Ente75/Wikipedia

Since it was just a toe, the surgeon thought he could perform the operation without any help. The toe, unfortunately, had other plans. The partially anesthetized patient got restless in the operating room, but with no actual trained nurse in the vicinity, the surgeon asked the closest available person – that would be the janitor – to lend a hand.

The surgical manager heard about these goings-on and got to the operating room too late to stop the procedure but soon enough to see the cleaning staffer “at the operating table with a bloody suction cup and a bloody compress in their hands,” SWR recently reported.

The incident was reported to the hospital’s medical director and the surgeon was fired, but since the patient experienced no complications not much fuss was made about it at the time.

Well, guess what? It’s toe-tally our job to make a fuss about these kinds of things. Or could it be that our job, much like the surgeon’s employment and the patient’s digit, is here toe-day and gone toe-morrow?

Even the plague wanted to visit Stonehenge

We’re about to blow your mind: The history you learned in school was often inaccurate. Shocking, we know, so we’ll give you a minute to process this incredible news.

Better? Good. Now, let’s look back at high school European history. The Black Death, specifically. The common narrative is that the Mongols, while besieging a Crimean city belonging to the Genoese, catapulted dead bodies infected with some mystery disease that turned out to be the plague. The Genoese then brought the plague back to Italy, and from there, we all know the rest of the story.

Ian Hodkinson, [email protected]

The Black Death was certainly extremely important to the development of modern Europe as we know it, but the history books gloss over the much longer history of the plague. Yersinia pestis did not suddenly appear unbidden in a Mongol war camp in 1347. The Black Death wasn’t even the first horrific, continent-wide pandemic caused by the plague; the Plague of Justinian 800 years earlier crippled the Byzantine Empire during an expansionist phase and killed anywhere between 15 million and 100 million.

Today, though, LOTME looks even deeper into history, nearly beyond even history itself, back into the depths of early Bronze Age northern Europe. Specifically, to two ancient burial sites in England, where researchers have identified three 4,000-year-old cases of Y. pestis, the first recorded incidence of the disease in Britain.

Two of the individuals, identified through analysis of dental pulp, were young children buried at a mass grave in Somerset, while the third, a middle-aged woman, was found in a ring cairn in Cumbria. These sites are hundreds of miles apart, yet carbon dating suggests all three people lived and died at roughly the same time. The strain found is very similar to other samples of plague found across central and western Europe starting around 3,000 BCE, suggesting a single, easily spread disease affecting a large area in a relatively small period of time. In other words, a pandemic. Even in these ancient times, the world was connected. Not even the island of Britain could escape.

Beyond that though, the research helps confirm the cyclical nature of the plague; over time, it loses its effectiveness and goes into hiding, only to mutate and come roaring back. This is a story with absolutely no relevance at all to the modern world. Nope, no plagues or pandemics going around right now, no viruses fading into the background in any way. What a ridiculous inference to make.
 

Uncovering the invisible with artificial intelligence

This week in “What Else Can AI Do?” new research shows that a computer program can reveal brain injury that couldn’t be seen before with typical MRI.

The hot new AI, birthed by researchers at New York University, could potentially be a game changer by linking repeated head impacts with tiny, structural changes in the brains of athletes who have not been diagnosed with a concussion. By using machine learning to train the AI, the researchers were, for the first time, able to distinguish the brain of athletes who played contact sports (football, soccer, lacrosse) from those participating in noncontact sports such as baseball, basketball, and cross-country.

Andrea Danti/Thinkstock

How did they do it? The investigators “designed statistical techniques that gave their computer program the ability to ‘learn’ how to predict exposure to repeated head impacts using mathematical models,” they explained in a written statement. Adding in data from the MRI scans of 81 male athletes with no known concussion diagnosis and the ability to identify unusual brain features between athletes with and without head trauma allowed the AI to predict results with accuracy even Miss Cleo would envy.

“This method may provide an important diagnostic tool not only for concussion, but also for detecting the damage that stems from subtler and more frequent head impacts,” said lead author Junbo Chen, an engineering doctoral candidate at NYU. That could make this new AI a valuable asset to science and medicine.

There are many things the human brain can do that AI can’t, and delegation could be one of them. Examining the data that represent the human brain in minute detail? Maybe we leave that to the machine.
 

Talk about your field promotions

If you’re a surgeon doing an amputation, the list of possible assistants pretty much starts and ends in only one place: Not the closest available janitor.

That may seem like an oddly obvious thing for us to say, but there’s at least one former Mainz (Germany) University Hospital physician who really needed to get this bit of advice before he attempted an unassisted toe amputation back in October of 2020. Yes, that does seem like kind of a long time ago for us to be reporting it now, but the details of the incident only just came to light a few days ago, thanks to German public broadcaster SWR.

Ente75/Wikipedia

Since it was just a toe, the surgeon thought he could perform the operation without any help. The toe, unfortunately, had other plans. The partially anesthetized patient got restless in the operating room, but with no actual trained nurse in the vicinity, the surgeon asked the closest available person – that would be the janitor – to lend a hand.

The surgical manager heard about these goings-on and got to the operating room too late to stop the procedure but soon enough to see the cleaning staffer “at the operating table with a bloody suction cup and a bloody compress in their hands,” SWR recently reported.

The incident was reported to the hospital’s medical director and the surgeon was fired, but since the patient experienced no complications not much fuss was made about it at the time.

Well, guess what? It’s toe-tally our job to make a fuss about these kinds of things. Or could it be that our job, much like the surgeon’s employment and the patient’s digit, is here toe-day and gone toe-morrow?

Even the plague wanted to visit Stonehenge

We’re about to blow your mind: The history you learned in school was often inaccurate. Shocking, we know, so we’ll give you a minute to process this incredible news.

Better? Good. Now, let’s look back at high school European history. The Black Death, specifically. The common narrative is that the Mongols, while besieging a Crimean city belonging to the Genoese, catapulted dead bodies infected with some mystery disease that turned out to be the plague. The Genoese then brought the plague back to Italy, and from there, we all know the rest of the story.

Ian Hodkinson, [email protected]

The Black Death was certainly extremely important to the development of modern Europe as we know it, but the history books gloss over the much longer history of the plague. Yersinia pestis did not suddenly appear unbidden in a Mongol war camp in 1347. The Black Death wasn’t even the first horrific, continent-wide pandemic caused by the plague; the Plague of Justinian 800 years earlier crippled the Byzantine Empire during an expansionist phase and killed anywhere between 15 million and 100 million.

Today, though, LOTME looks even deeper into history, nearly beyond even history itself, back into the depths of early Bronze Age northern Europe. Specifically, to two ancient burial sites in England, where researchers have identified three 4,000-year-old cases of Y. pestis, the first recorded incidence of the disease in Britain.

Two of the individuals, identified through analysis of dental pulp, were young children buried at a mass grave in Somerset, while the third, a middle-aged woman, was found in a ring cairn in Cumbria. These sites are hundreds of miles apart, yet carbon dating suggests all three people lived and died at roughly the same time. The strain found is very similar to other samples of plague found across central and western Europe starting around 3,000 BCE, suggesting a single, easily spread disease affecting a large area in a relatively small period of time. In other words, a pandemic. Even in these ancient times, the world was connected. Not even the island of Britain could escape.

Beyond that though, the research helps confirm the cyclical nature of the plague; over time, it loses its effectiveness and goes into hiding, only to mutate and come roaring back. This is a story with absolutely no relevance at all to the modern world. Nope, no plagues or pandemics going around right now, no viruses fading into the background in any way. What a ridiculous inference to make.
 

Uncovering the invisible with artificial intelligence

This week in “What Else Can AI Do?” new research shows that a computer program can reveal brain injury that couldn’t be seen before with typical MRI.

The hot new AI, birthed by researchers at New York University, could potentially be a game changer by linking repeated head impacts with tiny, structural changes in the brains of athletes who have not been diagnosed with a concussion. By using machine learning to train the AI, the researchers were, for the first time, able to distinguish the brain of athletes who played contact sports (football, soccer, lacrosse) from those participating in noncontact sports such as baseball, basketball, and cross-country.

Andrea Danti/Thinkstock

How did they do it? The investigators “designed statistical techniques that gave their computer program the ability to ‘learn’ how to predict exposure to repeated head impacts using mathematical models,” they explained in a written statement. Adding in data from the MRI scans of 81 male athletes with no known concussion diagnosis and the ability to identify unusual brain features between athletes with and without head trauma allowed the AI to predict results with accuracy even Miss Cleo would envy.

“This method may provide an important diagnostic tool not only for concussion, but also for detecting the damage that stems from subtler and more frequent head impacts,” said lead author Junbo Chen, an engineering doctoral candidate at NYU. That could make this new AI a valuable asset to science and medicine.

There are many things the human brain can do that AI can’t, and delegation could be one of them. Examining the data that represent the human brain in minute detail? Maybe we leave that to the machine.
 

Talk about your field promotions

If you’re a surgeon doing an amputation, the list of possible assistants pretty much starts and ends in only one place: Not the closest available janitor.

That may seem like an oddly obvious thing for us to say, but there’s at least one former Mainz (Germany) University Hospital physician who really needed to get this bit of advice before he attempted an unassisted toe amputation back in October of 2020. Yes, that does seem like kind of a long time ago for us to be reporting it now, but the details of the incident only just came to light a few days ago, thanks to German public broadcaster SWR.

Ente75/Wikipedia

Since it was just a toe, the surgeon thought he could perform the operation without any help. The toe, unfortunately, had other plans. The partially anesthetized patient got restless in the operating room, but with no actual trained nurse in the vicinity, the surgeon asked the closest available person – that would be the janitor – to lend a hand.

The surgical manager heard about these goings-on and got to the operating room too late to stop the procedure but soon enough to see the cleaning staffer “at the operating table with a bloody suction cup and a bloody compress in their hands,” SWR recently reported.

The incident was reported to the hospital’s medical director and the surgeon was fired, but since the patient experienced no complications not much fuss was made about it at the time.

Well, guess what? It’s toe-tally our job to make a fuss about these kinds of things. Or could it be that our job, much like the surgeon’s employment and the patient’s digit, is here toe-day and gone toe-morrow?

Nearly one in five U.S. adults with type 2 diabetes but without symptoms of cardiovascular disease (CVD) have a clinically meaningful elevation of a marker of cardiac damage – namely, high-sensitivity cardiac troponin T (hs-cTnT) – based on data from a representative sample of more than 10,000 U.S. adults.

The finding suggests hs-cTnT maybe a useful marker for adults with diabetes who could benefit from more aggressive CVD risk reduction despite having no clinical indications of CVD.

The results “highlight the substantial burden of subclinical CVD in persons with diabetes and emphasize the importance of early detection and treatment of CVD for this high-risk population,” say the authors of the research, published in the Journal of the American Heart Association.

Johns Hopkins University

“This is the first study to examine subclinical CVD, defined by elevated cardiac biomarkers, in a nationally representative population of adults with or without diabetes. It provides novel information on the high burden of subclinical CVD [in American adults with diabetes] and the potential utility of hs-cTnT for monitoring this risk in people with diabetes,” said Elizabeth Selvin, PhD, senior author and a professor of epidemiology at Johns Hopkins University, Baltimore.

“What we are seeing is that many people with type 2 diabetes who have not had a heart attack or a history of cardiovascular disease are at high risk for cardiovascular complications,” added Dr. Selvin in an AHA press release. “When we look at the whole population of people diagnosed with type 2 diabetes, about 27 million adults in the U.S., according to the [Centers for Disease Control and Prevention], some are at low risk and some are at high risk for cardiovascular disease, so the open question is: ‘Who is most at risk?’ These cardiac biomarkers give us a window into cardiovascular risk in people who otherwise might not be recognized as highest risk.”

“Our results provide evidence to support use of cardiac biomarkers for routine risk monitoring in high-risk populations such as people with diabetes,” Dr. Selvin noted in an interview.
 

Need for aggressive CVD risk reduction

The findings also indicate that people with diabetes and an elevated hs-cTnT “should be targeted for aggressive cardiovascular risk reduction, including lifestyle interventions, weight loss, and treatment with statins, blood pressure medications, and cardioprotective therapies such as sodium-glucose cotransporter 2 (SGLT-2) inhibitors and glucagonlike peptide-1 (GLP-1) receptor agonists,” Dr. Selvin added.

“Cholesterol is often the factor that we target to reduce the risk of cardiovascular disease in people with type 2 diabetes,” she observed. “However, type 2 diabetes may have a direct effect on the heart not related to cholesterol levels. If type 2 diabetes is directly causing damage to the small vessels in the heart unrelated to cholesterol plaque buildup, then cholesterol-lowering medications are not going to prevent cardiac damage,” Dr. Selvin explained. “Our research suggests that additional non–statin-related therapies are needed to lower the cardiovascular disease risk in people with type 2 diabetes.”

However, she noted that a necessary step prior to formally recommending such a strategy is to run clinical trials to assess the efficacy of specific treatments, such as SGLT-2 inhibitors and GLP-1 agonists, in people with diabetes and elevated hs-cTnT.

“Randomized controlled trials would be best to test the relevance of measuring these biomarkers to assess risk in asymptomatic people with diabetes,” as well as prospective study of the value of hs-cTnT to guide treatment, commented Robert H. Eckel, MD, an endocrinologist affiliated with the University of Colorado at Denver, Aurora.

“I doubt measurements [of hs-cTnT] would be reimbursed [by third-party payers] if carried out without such outcome data,” he added.

Dr. Eckel also highlights the need to further validate in additional cohorts the link between elevations in hs-cTnT and CVD events in adults with diabetes, and to confirm that elevated levels of another cardiac biomarker – N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) – do not work as well as troponin as a risk marker for people with diabetes, another finding of the study.
 

ADA report already recommends testing these biomarkers for HF

However, a consensus report published in 2022 by the American Diabetes Association laid out the case for routinely and regularly measuring levels of both high sensitivity cardiac troponin and natriuretic peptides in people with diabetes for early identification of incident heart failure.

“Among individuals with diabetes, measurement of a natriuretic peptide or high-sensitivity cardiac troponin is recommended on at least a yearly basis to identify the earliest heart failure stages and implement strategies to prevent transition to symptomatic heart failure,” noted the ADA consensus report on heart failure.

The new study run by Dr. Selvin and coauthors used data collected by the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2004 from U.S. adults who were at least 20 years old and had no history of CVD: myocardial infarction, stroke, coronary heart disease, or heart failure. This included 9,273 people without diabetes and 1,031 with diabetes, defined as a prior diagnosis or hemoglobin A1c of at least 6.5%.

“Cardiovascular risk varies substantially in adults with type 2 diabetes, highlighting the need for accurate risk stratification,” the authors observed.

All study participants had recorded measures of hs-cTnT and NT-proBNP.

The researchers considered an hs-cTnT level of greater than 14 ng/L and an NT-proBNP level of greater than 125 pg/mL as indicators of subclinical CVD.

The crude prevalence of elevated NT-proBNP was 33.4% among those with diabetes and 16.1% in those without diabetes. Elevated hs-cTnT occurred in 19% of those with diabetes and in 5% of those without diabetes. Elevated levels of both markers existed in 9% of those with diabetes and in 3% of those without diabetes.

“Approximately one in three adults with diabetes had subclinical CVD, with 19% having elevated levels of hs-cTnT, 23% having elevated NT-proBNP, and 9% having elevations in both cardiac biomarkers,” the researchers noted.
 

Diabetes linked with a doubled prevalence of elevated hs-cTnT 

After adjustment for several demographic variables as well as traditional CVD risk factors, people with diabetes had a significant 98% higher rate of elevated hs-cTnT, compared with those without diabetes. But after similar adjustments, the rate of elevated NT-proBNP was significantly lower among people with diabetes, compared with controls, by a relative reduction of 24%.

“Our findings suggest that, in people with diabetes, hs-cTnT may be more useful [than NT-proBNP] for general risk monitoring, as its interpretation is less complicated,” said Dr. Selvin, who explained that “NT-proBNP is affected by overweight and obesity.”

In people with diabetes, the age-adjusted prevalence of elevated hs-cTnT ran higher in those with longer duration diabetes, and in those with less well-controlled diabetes based on a higher level of A1c. Neither of these factors showed any significant relationship with measured levels of NT-proBNP.

Further analysis linked the NHANES findings during 1999-2004 with U.S. national death records through the end of 2019. This showed that elevated levels of both hs-cTnT and NT-proBNP significantly linked with subsequently higher rates of all-cause mortality among people with diabetes. Elevated hs-cTnT linked with a 77% increased mortality and NT-proBNP linked with a 78% increased rate, compared with people with diabetes and no elevations in these markers, after adjustment for demographic variables and CVD risk factors.

However, for the outcome of cardiovascular death, elevated hs-cTnT linked with a nonsignificant 54% relative increase, while elevated NT-proBNP linked with a significant 2.46-fold relative increase.

The study “adds new data on biomarkers that are not routinely measured in asymptomatic people with or without diabetes” and the relationships of these markers to CVD mortality and all-cause mortality, Dr. Eckel concluded.

The study received no commercial funding, but used reagents donated by Abbott Laboratories, Ortho Clinical Diagnostics, Roche Diagnostics, and Siemens Healthcare Diagnostics. Dr. Selvin and Dr. Eckel had no disclosures.

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

Nearly one in five U.S. adults with type 2 diabetes but without symptoms of cardiovascular disease (CVD) have a clinically meaningful elevation of a marker of cardiac damage – namely, high-sensitivity cardiac troponin T (hs-cTnT) – based on data from a representative sample of more than 10,000 U.S. adults.

The finding suggests hs-cTnT maybe a useful marker for adults with diabetes who could benefit from more aggressive CVD risk reduction despite having no clinical indications of CVD.

The results “highlight the substantial burden of subclinical CVD in persons with diabetes and emphasize the importance of early detection and treatment of CVD for this high-risk population,” say the authors of the research, published in the Journal of the American Heart Association.

Johns Hopkins University

“This is the first study to examine subclinical CVD, defined by elevated cardiac biomarkers, in a nationally representative population of adults with or without diabetes. It provides novel information on the high burden of subclinical CVD [in American adults with diabetes] and the potential utility of hs-cTnT for monitoring this risk in people with diabetes,” said Elizabeth Selvin, PhD, senior author and a professor of epidemiology at Johns Hopkins University, Baltimore.

“What we are seeing is that many people with type 2 diabetes who have not had a heart attack or a history of cardiovascular disease are at high risk for cardiovascular complications,” added Dr. Selvin in an AHA press release. “When we look at the whole population of people diagnosed with type 2 diabetes, about 27 million adults in the U.S., according to the [Centers for Disease Control and Prevention], some are at low risk and some are at high risk for cardiovascular disease, so the open question is: ‘Who is most at risk?’ These cardiac biomarkers give us a window into cardiovascular risk in people who otherwise might not be recognized as highest risk.”

“Our results provide evidence to support use of cardiac biomarkers for routine risk monitoring in high-risk populations such as people with diabetes,” Dr. Selvin noted in an interview.
 

Need for aggressive CVD risk reduction

The findings also indicate that people with diabetes and an elevated hs-cTnT “should be targeted for aggressive cardiovascular risk reduction, including lifestyle interventions, weight loss, and treatment with statins, blood pressure medications, and cardioprotective therapies such as sodium-glucose cotransporter 2 (SGLT-2) inhibitors and glucagonlike peptide-1 (GLP-1) receptor agonists,” Dr. Selvin added.

“Cholesterol is often the factor that we target to reduce the risk of cardiovascular disease in people with type 2 diabetes,” she observed. “However, type 2 diabetes may have a direct effect on the heart not related to cholesterol levels. If type 2 diabetes is directly causing damage to the small vessels in the heart unrelated to cholesterol plaque buildup, then cholesterol-lowering medications are not going to prevent cardiac damage,” Dr. Selvin explained. “Our research suggests that additional non–statin-related therapies are needed to lower the cardiovascular disease risk in people with type 2 diabetes.”

However, she noted that a necessary step prior to formally recommending such a strategy is to run clinical trials to assess the efficacy of specific treatments, such as SGLT-2 inhibitors and GLP-1 agonists, in people with diabetes and elevated hs-cTnT.

“Randomized controlled trials would be best to test the relevance of measuring these biomarkers to assess risk in asymptomatic people with diabetes,” as well as prospective study of the value of hs-cTnT to guide treatment, commented Robert H. Eckel, MD, an endocrinologist affiliated with the University of Colorado at Denver, Aurora.

“I doubt measurements [of hs-cTnT] would be reimbursed [by third-party payers] if carried out without such outcome data,” he added.

Dr. Eckel also highlights the need to further validate in additional cohorts the link between elevations in hs-cTnT and CVD events in adults with diabetes, and to confirm that elevated levels of another cardiac biomarker – N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) – do not work as well as troponin as a risk marker for people with diabetes, another finding of the study.
 

ADA report already recommends testing these biomarkers for HF

However, a consensus report published in 2022 by the American Diabetes Association laid out the case for routinely and regularly measuring levels of both high sensitivity cardiac troponin and natriuretic peptides in people with diabetes for early identification of incident heart failure.

“Among individuals with diabetes, measurement of a natriuretic peptide or high-sensitivity cardiac troponin is recommended on at least a yearly basis to identify the earliest heart failure stages and implement strategies to prevent transition to symptomatic heart failure,” noted the ADA consensus report on heart failure.

The new study run by Dr. Selvin and coauthors used data collected by the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2004 from U.S. adults who were at least 20 years old and had no history of CVD: myocardial infarction, stroke, coronary heart disease, or heart failure. This included 9,273 people without diabetes and 1,031 with diabetes, defined as a prior diagnosis or hemoglobin A1c of at least 6.5%.

“Cardiovascular risk varies substantially in adults with type 2 diabetes, highlighting the need for accurate risk stratification,” the authors observed.

All study participants had recorded measures of hs-cTnT and NT-proBNP.

The researchers considered an hs-cTnT level of greater than 14 ng/L and an NT-proBNP level of greater than 125 pg/mL as indicators of subclinical CVD.

The crude prevalence of elevated NT-proBNP was 33.4% among those with diabetes and 16.1% in those without diabetes. Elevated hs-cTnT occurred in 19% of those with diabetes and in 5% of those without diabetes. Elevated levels of both markers existed in 9% of those with diabetes and in 3% of those without diabetes.

“Approximately one in three adults with diabetes had subclinical CVD, with 19% having elevated levels of hs-cTnT, 23% having elevated NT-proBNP, and 9% having elevations in both cardiac biomarkers,” the researchers noted.
 

Diabetes linked with a doubled prevalence of elevated hs-cTnT 

After adjustment for several demographic variables as well as traditional CVD risk factors, people with diabetes had a significant 98% higher rate of elevated hs-cTnT, compared with those without diabetes. But after similar adjustments, the rate of elevated NT-proBNP was significantly lower among people with diabetes, compared with controls, by a relative reduction of 24%.

“Our findings suggest that, in people with diabetes, hs-cTnT may be more useful [than NT-proBNP] for general risk monitoring, as its interpretation is less complicated,” said Dr. Selvin, who explained that “NT-proBNP is affected by overweight and obesity.”

In people with diabetes, the age-adjusted prevalence of elevated hs-cTnT ran higher in those with longer duration diabetes, and in those with less well-controlled diabetes based on a higher level of A1c. Neither of these factors showed any significant relationship with measured levels of NT-proBNP.

Further analysis linked the NHANES findings during 1999-2004 with U.S. national death records through the end of 2019. This showed that elevated levels of both hs-cTnT and NT-proBNP significantly linked with subsequently higher rates of all-cause mortality among people with diabetes. Elevated hs-cTnT linked with a 77% increased mortality and NT-proBNP linked with a 78% increased rate, compared with people with diabetes and no elevations in these markers, after adjustment for demographic variables and CVD risk factors.

However, for the outcome of cardiovascular death, elevated hs-cTnT linked with a nonsignificant 54% relative increase, while elevated NT-proBNP linked with a significant 2.46-fold relative increase.

The study “adds new data on biomarkers that are not routinely measured in asymptomatic people with or without diabetes” and the relationships of these markers to CVD mortality and all-cause mortality, Dr. Eckel concluded.

The study received no commercial funding, but used reagents donated by Abbott Laboratories, Ortho Clinical Diagnostics, Roche Diagnostics, and Siemens Healthcare Diagnostics. Dr. Selvin and Dr. Eckel had no disclosures.

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

Nearly one in five U.S. adults with type 2 diabetes but without symptoms of cardiovascular disease (CVD) have a clinically meaningful elevation of a marker of cardiac damage – namely, high-sensitivity cardiac troponin T (hs-cTnT) – based on data from a representative sample of more than 10,000 U.S. adults.

The finding suggests hs-cTnT maybe a useful marker for adults with diabetes who could benefit from more aggressive CVD risk reduction despite having no clinical indications of CVD.

The results “highlight the substantial burden of subclinical CVD in persons with diabetes and emphasize the importance of early detection and treatment of CVD for this high-risk population,” say the authors of the research, published in the Journal of the American Heart Association.

Johns Hopkins University

“This is the first study to examine subclinical CVD, defined by elevated cardiac biomarkers, in a nationally representative population of adults with or without diabetes. It provides novel information on the high burden of subclinical CVD [in American adults with diabetes] and the potential utility of hs-cTnT for monitoring this risk in people with diabetes,” said Elizabeth Selvin, PhD, senior author and a professor of epidemiology at Johns Hopkins University, Baltimore.

“What we are seeing is that many people with type 2 diabetes who have not had a heart attack or a history of cardiovascular disease are at high risk for cardiovascular complications,” added Dr. Selvin in an AHA press release. “When we look at the whole population of people diagnosed with type 2 diabetes, about 27 million adults in the U.S., according to the [Centers for Disease Control and Prevention], some are at low risk and some are at high risk for cardiovascular disease, so the open question is: ‘Who is most at risk?’ These cardiac biomarkers give us a window into cardiovascular risk in people who otherwise might not be recognized as highest risk.”

“Our results provide evidence to support use of cardiac biomarkers for routine risk monitoring in high-risk populations such as people with diabetes,” Dr. Selvin noted in an interview.
 

Need for aggressive CVD risk reduction

The findings also indicate that people with diabetes and an elevated hs-cTnT “should be targeted for aggressive cardiovascular risk reduction, including lifestyle interventions, weight loss, and treatment with statins, blood pressure medications, and cardioprotective therapies such as sodium-glucose cotransporter 2 (SGLT-2) inhibitors and glucagonlike peptide-1 (GLP-1) receptor agonists,” Dr. Selvin added.

“Cholesterol is often the factor that we target to reduce the risk of cardiovascular disease in people with type 2 diabetes,” she observed. “However, type 2 diabetes may have a direct effect on the heart not related to cholesterol levels. If type 2 diabetes is directly causing damage to the small vessels in the heart unrelated to cholesterol plaque buildup, then cholesterol-lowering medications are not going to prevent cardiac damage,” Dr. Selvin explained. “Our research suggests that additional non–statin-related therapies are needed to lower the cardiovascular disease risk in people with type 2 diabetes.”

However, she noted that a necessary step prior to formally recommending such a strategy is to run clinical trials to assess the efficacy of specific treatments, such as SGLT-2 inhibitors and GLP-1 agonists, in people with diabetes and elevated hs-cTnT.

“Randomized controlled trials would be best to test the relevance of measuring these biomarkers to assess risk in asymptomatic people with diabetes,” as well as prospective study of the value of hs-cTnT to guide treatment, commented Robert H. Eckel, MD, an endocrinologist affiliated with the University of Colorado at Denver, Aurora.

“I doubt measurements [of hs-cTnT] would be reimbursed [by third-party payers] if carried out without such outcome data,” he added.

Dr. Eckel also highlights the need to further validate in additional cohorts the link between elevations in hs-cTnT and CVD events in adults with diabetes, and to confirm that elevated levels of another cardiac biomarker – N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) – do not work as well as troponin as a risk marker for people with diabetes, another finding of the study.
 

ADA report already recommends testing these biomarkers for HF

However, a consensus report published in 2022 by the American Diabetes Association laid out the case for routinely and regularly measuring levels of both high sensitivity cardiac troponin and natriuretic peptides in people with diabetes for early identification of incident heart failure.

“Among individuals with diabetes, measurement of a natriuretic peptide or high-sensitivity cardiac troponin is recommended on at least a yearly basis to identify the earliest heart failure stages and implement strategies to prevent transition to symptomatic heart failure,” noted the ADA consensus report on heart failure.

The new study run by Dr. Selvin and coauthors used data collected by the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2004 from U.S. adults who were at least 20 years old and had no history of CVD: myocardial infarction, stroke, coronary heart disease, or heart failure. This included 9,273 people without diabetes and 1,031 with diabetes, defined as a prior diagnosis or hemoglobin A1c of at least 6.5%.

“Cardiovascular risk varies substantially in adults with type 2 diabetes, highlighting the need for accurate risk stratification,” the authors observed.

All study participants had recorded measures of hs-cTnT and NT-proBNP.

The researchers considered an hs-cTnT level of greater than 14 ng/L and an NT-proBNP level of greater than 125 pg/mL as indicators of subclinical CVD.

The crude prevalence of elevated NT-proBNP was 33.4% among those with diabetes and 16.1% in those without diabetes. Elevated hs-cTnT occurred in 19% of those with diabetes and in 5% of those without diabetes. Elevated levels of both markers existed in 9% of those with diabetes and in 3% of those without diabetes.

“Approximately one in three adults with diabetes had subclinical CVD, with 19% having elevated levels of hs-cTnT, 23% having elevated NT-proBNP, and 9% having elevations in both cardiac biomarkers,” the researchers noted.
 

Diabetes linked with a doubled prevalence of elevated hs-cTnT 

After adjustment for several demographic variables as well as traditional CVD risk factors, people with diabetes had a significant 98% higher rate of elevated hs-cTnT, compared with those without diabetes. But after similar adjustments, the rate of elevated NT-proBNP was significantly lower among people with diabetes, compared with controls, by a relative reduction of 24%.

“Our findings suggest that, in people with diabetes, hs-cTnT may be more useful [than NT-proBNP] for general risk monitoring, as its interpretation is less complicated,” said Dr. Selvin, who explained that “NT-proBNP is affected by overweight and obesity.”

In people with diabetes, the age-adjusted prevalence of elevated hs-cTnT ran higher in those with longer duration diabetes, and in those with less well-controlled diabetes based on a higher level of A1c. Neither of these factors showed any significant relationship with measured levels of NT-proBNP.

Further analysis linked the NHANES findings during 1999-2004 with U.S. national death records through the end of 2019. This showed that elevated levels of both hs-cTnT and NT-proBNP significantly linked with subsequently higher rates of all-cause mortality among people with diabetes. Elevated hs-cTnT linked with a 77% increased mortality and NT-proBNP linked with a 78% increased rate, compared with people with diabetes and no elevations in these markers, after adjustment for demographic variables and CVD risk factors.

However, for the outcome of cardiovascular death, elevated hs-cTnT linked with a nonsignificant 54% relative increase, while elevated NT-proBNP linked with a significant 2.46-fold relative increase.

The study “adds new data on biomarkers that are not routinely measured in asymptomatic people with or without diabetes” and the relationships of these markers to CVD mortality and all-cause mortality, Dr. Eckel concluded.

The study received no commercial funding, but used reagents donated by Abbott Laboratories, Ortho Clinical Diagnostics, Roche Diagnostics, and Siemens Healthcare Diagnostics. Dr. Selvin and Dr. Eckel had no disclosures.

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

MANNHEIM, GERMANY – Contrary to expectations, individuals with familial hypercholesterolemia (FH) have rates of overweight and obesity that mirror the general population – rates that appear to have a substantial impact on these patients’ already increased risk of coronary artery disease, a registry analysis suggests.

Data on almost 36,000 individuals with FH were collated from an international registry, revealing that 55% of adults and 25% of children and adolescents with the homozygous form of FH had overweight or obesity. The figures for heterozygous FH were 52% and 27%, respectively.

Crucially, overweight or obesity was associated with substantially increased rates of coronary artery disease, particularly in persons with heterozygous FH, among whom adults with obesity faced a twofold increased risk, rising to more than sixfold in children and adolescents.

Moreover, “obesity is associated with a worse lipid profile, even from childhood, regardless of whether a patient is on medication,” said study presenter Amany Elshorbagy, DPhil, Cardiovascular Epidemiologist, department of primary care and public health, Imperial College London.

She added that, with the increased risk of coronary artery disease associated with heterozygous FH, the results showed that “together with lipid-lowering medication, weight management is needed.”

The research was presented at the annual meeting of the European Atherosclerosis Society.
 

Tended to be thin

Alberico L. Catapano, MD, PhD, director of cardiovascular research and of the Lipoproteins and Atherosclerosis Laboratory of IRCCS Multimedica, Milan, and past president of the EAS, said in an interview that, historically, few FH patients were overweight or obese; rather, they tended to be thin.

However, there is now “a trend for people with FH to show more diabetes and obesity,” with the “bottom line” being that, as they are already at increased risk of coronary artery disease, it pushes their risk up even further.

In other words, if a risk factor such as obesity is added “on top of the strongest risk factor, that is LDL cholesterol, it is not one plus one makes two, it is one plus one makes three,” he said.

As such, Dr. Catapano believes that the study is “very interesting,” because it further underlines the importance of weight management for individuals with increased LDL cholesterol, “especially when you have genetic forms, like FH.”

Dr. Catapano’s comments were echoed by session co-chair Ulrike Schatz, MD, leader of the lipidology specialty department at the University Hospital Carl Gustav Carus, Technical University of Dresden (Germany).

Indeed, she told Dr. Elshorbagy before her presentation that she finds “a lot of my FH patients have a tendency towards anorexia.”

In an interview, Dr. Elshorbagy said that that reaction was typical of “most of the clinicians” she had spoken to. Upon seeing her data, especially for homozygous FH patients, they say, “They are on the lean side.”

Consequently, the research team went into the study “with the expectation that they might have a lower prevalence of obesity and overweight than the general population,” but “that’s not what we’re seeing.”

Dr. Elshorbagy noted that it would be helpful to have longitudinal data to determine whether, 50 years ago, patients with HF “were leaner, along with the rest of the population.”

The registry data are cross-sectional, and the team is now reaching out to the respective national lead investigators to submit follow-up data on their patients, with the aim of looking at changes in body weight and the impact on outcomes over time.

Another key question for the researchers is in regard to fat distribution, as body mass index “is not the best predictor of heart disease,” Dr. Elshorbagy said, but is rather central obesity.

Although they have also asked investigators to share waist circumference data, she conceded that it is a measurement that “is a lot harder to standardize across centers and countries; it’s not like putting patients on a scale.”

Overall, Dr. Elshorbagy believes that her findings indicate that clinicians should take a broader, more holistic approach toward their patients – in other words, an approach in which lipid lowering medication is “key but is just one of several things we need to do to make sure the coronary event rate goes down.”
 

More with than without

Dr. Elshorbagy began her presentation by highlighting that the prevalence of overweight and obesity ranges from 50% to 70% and that it is “the only health condition where you’ve got more people worldwide with the condition than without.”

Crucially, overweight increases the risk of coronary artery disease by approximately 20%. Among patients with obesity, the risk rises to 50%.

Given that FH patients “already have a very high risk of cardiovascular disease from their high cholesterol levels,” the team set out to determine rates of obesity and overweight in this population and their impact on coronary artery disease risk.

They used cross-sectional data from the EAS FH Studies Collaboration Global Registry, which involves 29,262 adults aged greater than or equal to 18 years and 6,275 children and adolescents aged 5 to 17 years with heterozygous FH, and 325 adults and 57 children with homozygous FH.

Dividing the adults into standard BMI categories, they found that 16% of heterozygous and 23% of homozygous FH patients had obesity, while 52% and 55%, respectively, had overweight or obesity.

For children, the team used World Health Organization z score cutoffs, which indicated that 9% of patients with heterozygous FH and 7% of patients with homozygous FH had obesity. Rates of overweight or obesity were 27% and 25%, respectively.

Among patients with heterozygous FH, rates of overweight or obesity among adults were 50% in high-income countries and 63% in other countries; among children, the rates were and 27% and 29%, respectively.

Stratified by region, the team found that the lowest rate of overweight or obesity among adult patients with heterozygous FH was in Eastern Asia, at 27%, while the highest was in Northern Africa/Western Asia (the Middle East), at 82%.

In North America, 56% of adult patients had overweight or obesity. The prevalence of coronary artery disease rose with increasing BMI.

Among adult patients with heterozygous FH, 11.3% of those with normal weight had coronary artery disease; the percentage rose to 22.9% among those with overweight, and 30.9% among those with obesity. Among children, the corresponding figures were 0.1%, 0.2%, and 0.7%.

Putting adults and children with homozygous FH together, the researchers found that 29.0% of patients with normal weight had coronary artery disease, compared with 31.3% of those with overweight and 49.3% of those with obesity.

Moreover, the results showed that levels of LDL and remnant cholesterol were significantly associated with BMI in adults and children with heterozygous FH, even after adjusting for age, sex, and lipid-lowering medication (P < .001 for all).

Multivariate analysis that took into account age, sex, lipid-lowering medication, and LDL cholesterol revealed that having obesity, compared with not having obesity, was associated with a substantial increase in the risk of coronary artery disease among patients with heterozygous FH.

Among adults with the condition, the odds ratio was 2.16 (95% confidence interval, 1.97-2.36), while among children and adolescents, it was 6.87 (95% CI, 1.55-30.46).

The results remained similar after further adjustment for the presence of diabetes and when considering peripheral artery disease and stroke.

No funding for the study was declared. Dr. Elshorbagy has relationships with Amgen, Daiichi Sankyo, and Regeneron.

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

MANNHEIM, GERMANY – Contrary to expectations, individuals with familial hypercholesterolemia (FH) have rates of overweight and obesity that mirror the general population – rates that appear to have a substantial impact on these patients’ already increased risk of coronary artery disease, a registry analysis suggests.

Data on almost 36,000 individuals with FH were collated from an international registry, revealing that 55% of adults and 25% of children and adolescents with the homozygous form of FH had overweight or obesity. The figures for heterozygous FH were 52% and 27%, respectively.

Crucially, overweight or obesity was associated with substantially increased rates of coronary artery disease, particularly in persons with heterozygous FH, among whom adults with obesity faced a twofold increased risk, rising to more than sixfold in children and adolescents.

Moreover, “obesity is associated with a worse lipid profile, even from childhood, regardless of whether a patient is on medication,” said study presenter Amany Elshorbagy, DPhil, Cardiovascular Epidemiologist, department of primary care and public health, Imperial College London.

She added that, with the increased risk of coronary artery disease associated with heterozygous FH, the results showed that “together with lipid-lowering medication, weight management is needed.”

The research was presented at the annual meeting of the European Atherosclerosis Society.
 

Tended to be thin

Alberico L. Catapano, MD, PhD, director of cardiovascular research and of the Lipoproteins and Atherosclerosis Laboratory of IRCCS Multimedica, Milan, and past president of the EAS, said in an interview that, historically, few FH patients were overweight or obese; rather, they tended to be thin.

However, there is now “a trend for people with FH to show more diabetes and obesity,” with the “bottom line” being that, as they are already at increased risk of coronary artery disease, it pushes their risk up even further.

In other words, if a risk factor such as obesity is added “on top of the strongest risk factor, that is LDL cholesterol, it is not one plus one makes two, it is one plus one makes three,” he said.

As such, Dr. Catapano believes that the study is “very interesting,” because it further underlines the importance of weight management for individuals with increased LDL cholesterol, “especially when you have genetic forms, like FH.”

Dr. Catapano’s comments were echoed by session co-chair Ulrike Schatz, MD, leader of the lipidology specialty department at the University Hospital Carl Gustav Carus, Technical University of Dresden (Germany).

Indeed, she told Dr. Elshorbagy before her presentation that she finds “a lot of my FH patients have a tendency towards anorexia.”

In an interview, Dr. Elshorbagy said that that reaction was typical of “most of the clinicians” she had spoken to. Upon seeing her data, especially for homozygous FH patients, they say, “They are on the lean side.”

Consequently, the research team went into the study “with the expectation that they might have a lower prevalence of obesity and overweight than the general population,” but “that’s not what we’re seeing.”

Dr. Elshorbagy noted that it would be helpful to have longitudinal data to determine whether, 50 years ago, patients with HF “were leaner, along with the rest of the population.”

The registry data are cross-sectional, and the team is now reaching out to the respective national lead investigators to submit follow-up data on their patients, with the aim of looking at changes in body weight and the impact on outcomes over time.

Another key question for the researchers is in regard to fat distribution, as body mass index “is not the best predictor of heart disease,” Dr. Elshorbagy said, but is rather central obesity.

Although they have also asked investigators to share waist circumference data, she conceded that it is a measurement that “is a lot harder to standardize across centers and countries; it’s not like putting patients on a scale.”

Overall, Dr. Elshorbagy believes that her findings indicate that clinicians should take a broader, more holistic approach toward their patients – in other words, an approach in which lipid lowering medication is “key but is just one of several things we need to do to make sure the coronary event rate goes down.”
 

More with than without

Dr. Elshorbagy began her presentation by highlighting that the prevalence of overweight and obesity ranges from 50% to 70% and that it is “the only health condition where you’ve got more people worldwide with the condition than without.”

Crucially, overweight increases the risk of coronary artery disease by approximately 20%. Among patients with obesity, the risk rises to 50%.

Given that FH patients “already have a very high risk of cardiovascular disease from their high cholesterol levels,” the team set out to determine rates of obesity and overweight in this population and their impact on coronary artery disease risk.

They used cross-sectional data from the EAS FH Studies Collaboration Global Registry, which involves 29,262 adults aged greater than or equal to 18 years and 6,275 children and adolescents aged 5 to 17 years with heterozygous FH, and 325 adults and 57 children with homozygous FH.

Dividing the adults into standard BMI categories, they found that 16% of heterozygous and 23% of homozygous FH patients had obesity, while 52% and 55%, respectively, had overweight or obesity.

For children, the team used World Health Organization z score cutoffs, which indicated that 9% of patients with heterozygous FH and 7% of patients with homozygous FH had obesity. Rates of overweight or obesity were 27% and 25%, respectively.

Among patients with heterozygous FH, rates of overweight or obesity among adults were 50% in high-income countries and 63% in other countries; among children, the rates were and 27% and 29%, respectively.

Stratified by region, the team found that the lowest rate of overweight or obesity among adult patients with heterozygous FH was in Eastern Asia, at 27%, while the highest was in Northern Africa/Western Asia (the Middle East), at 82%.

In North America, 56% of adult patients had overweight or obesity. The prevalence of coronary artery disease rose with increasing BMI.

Among adult patients with heterozygous FH, 11.3% of those with normal weight had coronary artery disease; the percentage rose to 22.9% among those with overweight, and 30.9% among those with obesity. Among children, the corresponding figures were 0.1%, 0.2%, and 0.7%.

Putting adults and children with homozygous FH together, the researchers found that 29.0% of patients with normal weight had coronary artery disease, compared with 31.3% of those with overweight and 49.3% of those with obesity.

Moreover, the results showed that levels of LDL and remnant cholesterol were significantly associated with BMI in adults and children with heterozygous FH, even after adjusting for age, sex, and lipid-lowering medication (P < .001 for all).

Multivariate analysis that took into account age, sex, lipid-lowering medication, and LDL cholesterol revealed that having obesity, compared with not having obesity, was associated with a substantial increase in the risk of coronary artery disease among patients with heterozygous FH.

Among adults with the condition, the odds ratio was 2.16 (95% confidence interval, 1.97-2.36), while among children and adolescents, it was 6.87 (95% CI, 1.55-30.46).

The results remained similar after further adjustment for the presence of diabetes and when considering peripheral artery disease and stroke.

No funding for the study was declared. Dr. Elshorbagy has relationships with Amgen, Daiichi Sankyo, and Regeneron.

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

MANNHEIM, GERMANY – Contrary to expectations, individuals with familial hypercholesterolemia (FH) have rates of overweight and obesity that mirror the general population – rates that appear to have a substantial impact on these patients’ already increased risk of coronary artery disease, a registry analysis suggests.

Data on almost 36,000 individuals with FH were collated from an international registry, revealing that 55% of adults and 25% of children and adolescents with the homozygous form of FH had overweight or obesity. The figures for heterozygous FH were 52% and 27%, respectively.

Crucially, overweight or obesity was associated with substantially increased rates of coronary artery disease, particularly in persons with heterozygous FH, among whom adults with obesity faced a twofold increased risk, rising to more than sixfold in children and adolescents.

Moreover, “obesity is associated with a worse lipid profile, even from childhood, regardless of whether a patient is on medication,” said study presenter Amany Elshorbagy, DPhil, Cardiovascular Epidemiologist, department of primary care and public health, Imperial College London.

She added that, with the increased risk of coronary artery disease associated with heterozygous FH, the results showed that “together with lipid-lowering medication, weight management is needed.”

The research was presented at the annual meeting of the European Atherosclerosis Society.
 

Tended to be thin

Alberico L. Catapano, MD, PhD, director of cardiovascular research and of the Lipoproteins and Atherosclerosis Laboratory of IRCCS Multimedica, Milan, and past president of the EAS, said in an interview that, historically, few FH patients were overweight or obese; rather, they tended to be thin.

However, there is now “a trend for people with FH to show more diabetes and obesity,” with the “bottom line” being that, as they are already at increased risk of coronary artery disease, it pushes their risk up even further.

In other words, if a risk factor such as obesity is added “on top of the strongest risk factor, that is LDL cholesterol, it is not one plus one makes two, it is one plus one makes three,” he said.

As such, Dr. Catapano believes that the study is “very interesting,” because it further underlines the importance of weight management for individuals with increased LDL cholesterol, “especially when you have genetic forms, like FH.”

Dr. Catapano’s comments were echoed by session co-chair Ulrike Schatz, MD, leader of the lipidology specialty department at the University Hospital Carl Gustav Carus, Technical University of Dresden (Germany).

Indeed, she told Dr. Elshorbagy before her presentation that she finds “a lot of my FH patients have a tendency towards anorexia.”

In an interview, Dr. Elshorbagy said that that reaction was typical of “most of the clinicians” she had spoken to. Upon seeing her data, especially for homozygous FH patients, they say, “They are on the lean side.”

Consequently, the research team went into the study “with the expectation that they might have a lower prevalence of obesity and overweight than the general population,” but “that’s not what we’re seeing.”

Dr. Elshorbagy noted that it would be helpful to have longitudinal data to determine whether, 50 years ago, patients with HF “were leaner, along with the rest of the population.”

The registry data are cross-sectional, and the team is now reaching out to the respective national lead investigators to submit follow-up data on their patients, with the aim of looking at changes in body weight and the impact on outcomes over time.

Another key question for the researchers is in regard to fat distribution, as body mass index “is not the best predictor of heart disease,” Dr. Elshorbagy said, but is rather central obesity.

Although they have also asked investigators to share waist circumference data, she conceded that it is a measurement that “is a lot harder to standardize across centers and countries; it’s not like putting patients on a scale.”

Overall, Dr. Elshorbagy believes that her findings indicate that clinicians should take a broader, more holistic approach toward their patients – in other words, an approach in which lipid lowering medication is “key but is just one of several things we need to do to make sure the coronary event rate goes down.”
 

More with than without

Dr. Elshorbagy began her presentation by highlighting that the prevalence of overweight and obesity ranges from 50% to 70% and that it is “the only health condition where you’ve got more people worldwide with the condition than without.”

Crucially, overweight increases the risk of coronary artery disease by approximately 20%. Among patients with obesity, the risk rises to 50%.

Given that FH patients “already have a very high risk of cardiovascular disease from their high cholesterol levels,” the team set out to determine rates of obesity and overweight in this population and their impact on coronary artery disease risk.

They used cross-sectional data from the EAS FH Studies Collaboration Global Registry, which involves 29,262 adults aged greater than or equal to 18 years and 6,275 children and adolescents aged 5 to 17 years with heterozygous FH, and 325 adults and 57 children with homozygous FH.

Dividing the adults into standard BMI categories, they found that 16% of heterozygous and 23% of homozygous FH patients had obesity, while 52% and 55%, respectively, had overweight or obesity.

For children, the team used World Health Organization z score cutoffs, which indicated that 9% of patients with heterozygous FH and 7% of patients with homozygous FH had obesity. Rates of overweight or obesity were 27% and 25%, respectively.

Among patients with heterozygous FH, rates of overweight or obesity among adults were 50% in high-income countries and 63% in other countries; among children, the rates were and 27% and 29%, respectively.

Stratified by region, the team found that the lowest rate of overweight or obesity among adult patients with heterozygous FH was in Eastern Asia, at 27%, while the highest was in Northern Africa/Western Asia (the Middle East), at 82%.

In North America, 56% of adult patients had overweight or obesity. The prevalence of coronary artery disease rose with increasing BMI.

Among adult patients with heterozygous FH, 11.3% of those with normal weight had coronary artery disease; the percentage rose to 22.9% among those with overweight, and 30.9% among those with obesity. Among children, the corresponding figures were 0.1%, 0.2%, and 0.7%.

Putting adults and children with homozygous FH together, the researchers found that 29.0% of patients with normal weight had coronary artery disease, compared with 31.3% of those with overweight and 49.3% of those with obesity.

Moreover, the results showed that levels of LDL and remnant cholesterol were significantly associated with BMI in adults and children with heterozygous FH, even after adjusting for age, sex, and lipid-lowering medication (P < .001 for all).

Multivariate analysis that took into account age, sex, lipid-lowering medication, and LDL cholesterol revealed that having obesity, compared with not having obesity, was associated with a substantial increase in the risk of coronary artery disease among patients with heterozygous FH.

Among adults with the condition, the odds ratio was 2.16 (95% confidence interval, 1.97-2.36), while among children and adolescents, it was 6.87 (95% CI, 1.55-30.46).

The results remained similar after further adjustment for the presence of diabetes and when considering peripheral artery disease and stroke.

No funding for the study was declared. Dr. Elshorbagy has relationships with Amgen, Daiichi Sankyo, and Regeneron.

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

MUNICH, GERMANY – Anticoagulation using apixaban (Eliquis) offers no benefit over aspirin in patients with embolic stroke of undetermined source (ESUS) who have atrial cardiopathy but no overt atrial fibrillation, suggest findings from the ARCADIA trial.

The trial, which was halted early, randomized more than 1,000 ESUS patients with atrial cardiomyopathy to apixaban or placebo. Results showed that apixaban did not improve rates of recurrent stroke of any kind nor safety outcomes such as major hemorrhage and all-cause mortality.

The results were presented at the annual meeting of the European Stroke Organisation Conference.

“We found no benefit of apixaban over aspirin in patients with ESUS who had evidence of atrial cardiopathy, at least based on the criteria in our trial,” said study presenter Hooman Kamel, MD, MS, vice chair for research and chief of neurocritical care in the department of neurology, Weill Cornell Medicine, New York.

“It could be that this concept of thrombogenic atrial cardiopathy really isn’t present unless there is also atrial fibrillation,” he continued, suggesting alternatively that results may be caused by the “incorrect choice of atrial cardiopathy biomarkers or thresholds.”

“We chose these because they were clinically scalable and usable in a multicenter design,” Dr. Kamel explained, adding that there are a number of different proposed biomarkers that could be used in a future study.

The team will now perform secondary analyses over the coming months to “try to help sort out some of these potential explanations.”

Dr. Kamel concluded, however, that, “as of now, no strategy of anticoagulation has been found to be better than antiplatelet therapy for secondary stroke prevention after ESUS.”
 

Similar results

Approached for comment, session cochair Robin Lemmens, MD, PhD, a neurologist in the department of neurosciences, UZ Leuven (Belgium), noted that this is the third ESUS trial, after the NAVIGATE and RE-SPECT trials, and they have all showed “similar results.”

He said, however, that there “could be various reasons for that, and it’s good that they mentioned looking into the subgroups,” as has been done for those other studies.

“Most of these trials were initiated under the concept that most of these patients would have had underlying atrial fibrillation, and then of course there would have been a benefit for anticoagulation.”

“It turns out that that’s not the case,” Dr. Lemmens said, “probably because there’s a lot of heterogeneity in these patients,” with different reasons for developing stroke, “not just only potentially underlying atrial fibrillation.”

Session cochair Arthur Liesz, MD, PhD, Institute for Stroke and Dementia Research, University Hospital, LMU Munich, added that it is important to consider the definition of atrial cardiopathy in this context.

If this was limited only to structural cardiopathy, then this “was a rather small subpopulation in this study,” he said in an interview.

Dr. Liesz said that it could instead have been conducted with “more stringent cutoffs,” and could have considered blood biomarkers, “which then would have delivered more overlap with structural cardiopathy,” and allowed those patients to be analyzed separately.
 

Heterogeneous etiologies?

Dr. Kamel began by noting that the failure of NAVIGATE and RESPECT to show a benefit from anticoagulation in the prevention of recurrent stroke in patients with ESUS led to the hypothesis that this is “perhaps due to heterogeneous underlying etiologies.”

Moreover, these etiologies “may require different types of antithrombotic therapy to best prevent recurrence, and one such underlying etiology may be atrial cardiopathy.”

He explained that several observational studies have found, in the absence of atrial fibrillation, associations between stroke and different markers of atrial cardiopathy and, “given the proven benefit of anticoagulation in preventing strokes in patients with atrial fibrillation, it seems plausible” that they may also benefit.

To investigate further, the team conducted ARCADIA, an investigator-initiated, multicenter, randomized trial involving patients aged 45 years and older from 185 sites in the United States and Canada with a clinical diagnosis of stroke that met the consensus criteria for ESUS.

They also were required to have undergone brain imaging to rule out hemorrhagic stroke, and to have a modified Rankin Scale score of 4 or less, indicating up to a moderately severe degree of disability.

They also had atrial cardiopathy, as determined by P-wave terminal force in V1 greater than 5,000mcV*ms on electrocardiography, serum N-terminal prohormone of brain natriuretic peptide levels greater than 250 pg/mL, or a left atrium diameter of at least 3 cm/m².

The patients were randomly assigned to apixaban 5 mg or 2.5 mg twice daily plus aspirin placebo, or apixaban placebo plus aspirin 81 mg daily. Those diagnosed with atrial fibrillation after randomization crossed over to open-label anticoagulant therapy at physician discretion.

Dr. Kamel reported that, in 2022, after enrollment of 1015 patients with a mean follow-up of 1.8 years, the trial was halted at the planned interim efficacy/futility analysis, adding that there were “no safety concerns.”

The apixaban and aspirin groups were well balanced in terms of their baseline characteristics. The mean age was 68 years, and 54% were female. Three-quarters of the participants were White; 21.1% were Black.

Prior stroke was reported in 19% of patients. Hypertension was common, in about 77%, and type 2 diabetes was seen in 31%. There were relatively few cases of ischemic heart disease, heart failure, and peripheral arterial disease.

The primary efficacy outcome of recurrent stroke of any type occurred in 4.4% of both patients treated with apixaban and those given aspirin, at a hazard ratio of 1.00 (95% confidence interval, 0.64-1.55). Similar findings were seen when looking individually at ischemic and hemorrhagic stroke, and stroke of undetermined type.

There was also no significant difference in the secondary outcomes of recurrent ischemic stroke or systemic embolism, at 4.1% versus 4.4% (HR, 0.92; 95% CI, 0.59-1.44), and recurrent stroke of any type or death from any cause, at 7.3% versus 6.8% (HR, 1.08; 95% CI, 0.76-1.52).

In terms of safety, rates of major hemorrhage were low and almost identical between the groups, at 0.7% with apixaban and 0.8% for aspirin (HR, 1.02; 95% CI, 0.29-3.51), and were similar for all-cause mortality, at 1.8% versus 1.2% (HR, 1.53; 95% CI, 0.63-3.74).

Proportionately more patients treated with aspirin experienced symptomatic intracranial hemorrhage, at 1.1% versus 0%.

The trial results generated a flurry of interest on Twitter.

Thomas Ford, MD, a vascular neurology fellow from Boston Medical Center, described the results as “disappointing,” although he was “curious to see if there was any signal of benefit in subgroup analyses.”

Shadi Yaghi, codirector of the Comprehensive Stroke Center at Brown University, Providence, R.I., added that the trial “begs the question [as to] whether all device-detected atrial fibrillation warrants anticoagulation.”

Replying, Mitchell Elkind, MD, MPhil, professor of neurology and epidemiology at Columbia University Irving Medical Center, New York, said that he agrees with this interpretation.

“Maybe the issue is not with the concept of atrial cardiopathy but with the need to [anticoagulate] all patients with low [atrial fibrillation] burden or incidental [atrial fibrillation] after stroke.”

The study was funded by the National Institutes of Health and the National Institute of Neurological Disorders and Stroke. The study drug was provided in kind by BMS-Pfizer, and ancillary funding for the NTproBNP assays was provided by Roche. No relevant financial relationships were reported.

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

MUNICH, GERMANY – Anticoagulation using apixaban (Eliquis) offers no benefit over aspirin in patients with embolic stroke of undetermined source (ESUS) who have atrial cardiopathy but no overt atrial fibrillation, suggest findings from the ARCADIA trial.

The trial, which was halted early, randomized more than 1,000 ESUS patients with atrial cardiomyopathy to apixaban or placebo. Results showed that apixaban did not improve rates of recurrent stroke of any kind nor safety outcomes such as major hemorrhage and all-cause mortality.

The results were presented at the annual meeting of the European Stroke Organisation Conference.

“We found no benefit of apixaban over aspirin in patients with ESUS who had evidence of atrial cardiopathy, at least based on the criteria in our trial,” said study presenter Hooman Kamel, MD, MS, vice chair for research and chief of neurocritical care in the department of neurology, Weill Cornell Medicine, New York.

“It could be that this concept of thrombogenic atrial cardiopathy really isn’t present unless there is also atrial fibrillation,” he continued, suggesting alternatively that results may be caused by the “incorrect choice of atrial cardiopathy biomarkers or thresholds.”

“We chose these because they were clinically scalable and usable in a multicenter design,” Dr. Kamel explained, adding that there are a number of different proposed biomarkers that could be used in a future study.

The team will now perform secondary analyses over the coming months to “try to help sort out some of these potential explanations.”

Dr. Kamel concluded, however, that, “as of now, no strategy of anticoagulation has been found to be better than antiplatelet therapy for secondary stroke prevention after ESUS.”
 

Similar results

Approached for comment, session cochair Robin Lemmens, MD, PhD, a neurologist in the department of neurosciences, UZ Leuven (Belgium), noted that this is the third ESUS trial, after the NAVIGATE and RE-SPECT trials, and they have all showed “similar results.”

He said, however, that there “could be various reasons for that, and it’s good that they mentioned looking into the subgroups,” as has been done for those other studies.

“Most of these trials were initiated under the concept that most of these patients would have had underlying atrial fibrillation, and then of course there would have been a benefit for anticoagulation.”

“It turns out that that’s not the case,” Dr. Lemmens said, “probably because there’s a lot of heterogeneity in these patients,” with different reasons for developing stroke, “not just only potentially underlying atrial fibrillation.”

Session cochair Arthur Liesz, MD, PhD, Institute for Stroke and Dementia Research, University Hospital, LMU Munich, added that it is important to consider the definition of atrial cardiopathy in this context.

If this was limited only to structural cardiopathy, then this “was a rather small subpopulation in this study,” he said in an interview.

Dr. Liesz said that it could instead have been conducted with “more stringent cutoffs,” and could have considered blood biomarkers, “which then would have delivered more overlap with structural cardiopathy,” and allowed those patients to be analyzed separately.
 

Heterogeneous etiologies?

Dr. Kamel began by noting that the failure of NAVIGATE and RESPECT to show a benefit from anticoagulation in the prevention of recurrent stroke in patients with ESUS led to the hypothesis that this is “perhaps due to heterogeneous underlying etiologies.”

Moreover, these etiologies “may require different types of antithrombotic therapy to best prevent recurrence, and one such underlying etiology may be atrial cardiopathy.”

He explained that several observational studies have found, in the absence of atrial fibrillation, associations between stroke and different markers of atrial cardiopathy and, “given the proven benefit of anticoagulation in preventing strokes in patients with atrial fibrillation, it seems plausible” that they may also benefit.

To investigate further, the team conducted ARCADIA, an investigator-initiated, multicenter, randomized trial involving patients aged 45 years and older from 185 sites in the United States and Canada with a clinical diagnosis of stroke that met the consensus criteria for ESUS.

They also were required to have undergone brain imaging to rule out hemorrhagic stroke, and to have a modified Rankin Scale score of 4 or less, indicating up to a moderately severe degree of disability.

They also had atrial cardiopathy, as determined by P-wave terminal force in V1 greater than 5,000mcV*ms on electrocardiography, serum N-terminal prohormone of brain natriuretic peptide levels greater than 250 pg/mL, or a left atrium diameter of at least 3 cm/m².

The patients were randomly assigned to apixaban 5 mg or 2.5 mg twice daily plus aspirin placebo, or apixaban placebo plus aspirin 81 mg daily. Those diagnosed with atrial fibrillation after randomization crossed over to open-label anticoagulant therapy at physician discretion.

Dr. Kamel reported that, in 2022, after enrollment of 1015 patients with a mean follow-up of 1.8 years, the trial was halted at the planned interim efficacy/futility analysis, adding that there were “no safety concerns.”

The apixaban and aspirin groups were well balanced in terms of their baseline characteristics. The mean age was 68 years, and 54% were female. Three-quarters of the participants were White; 21.1% were Black.

Prior stroke was reported in 19% of patients. Hypertension was common, in about 77%, and type 2 diabetes was seen in 31%. There were relatively few cases of ischemic heart disease, heart failure, and peripheral arterial disease.

The primary efficacy outcome of recurrent stroke of any type occurred in 4.4% of both patients treated with apixaban and those given aspirin, at a hazard ratio of 1.00 (95% confidence interval, 0.64-1.55). Similar findings were seen when looking individually at ischemic and hemorrhagic stroke, and stroke of undetermined type.

There was also no significant difference in the secondary outcomes of recurrent ischemic stroke or systemic embolism, at 4.1% versus 4.4% (HR, 0.92; 95% CI, 0.59-1.44), and recurrent stroke of any type or death from any cause, at 7.3% versus 6.8% (HR, 1.08; 95% CI, 0.76-1.52).

In terms of safety, rates of major hemorrhage were low and almost identical between the groups, at 0.7% with apixaban and 0.8% for aspirin (HR, 1.02; 95% CI, 0.29-3.51), and were similar for all-cause mortality, at 1.8% versus 1.2% (HR, 1.53; 95% CI, 0.63-3.74).

Proportionately more patients treated with aspirin experienced symptomatic intracranial hemorrhage, at 1.1% versus 0%.

The trial results generated a flurry of interest on Twitter.

Thomas Ford, MD, a vascular neurology fellow from Boston Medical Center, described the results as “disappointing,” although he was “curious to see if there was any signal of benefit in subgroup analyses.”

Shadi Yaghi, codirector of the Comprehensive Stroke Center at Brown University, Providence, R.I., added that the trial “begs the question [as to] whether all device-detected atrial fibrillation warrants anticoagulation.”

Replying, Mitchell Elkind, MD, MPhil, professor of neurology and epidemiology at Columbia University Irving Medical Center, New York, said that he agrees with this interpretation.

“Maybe the issue is not with the concept of atrial cardiopathy but with the need to [anticoagulate] all patients with low [atrial fibrillation] burden or incidental [atrial fibrillation] after stroke.”

The study was funded by the National Institutes of Health and the National Institute of Neurological Disorders and Stroke. The study drug was provided in kind by BMS-Pfizer, and ancillary funding for the NTproBNP assays was provided by Roche. No relevant financial relationships were reported.

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

MUNICH, GERMANY – Anticoagulation using apixaban (Eliquis) offers no benefit over aspirin in patients with embolic stroke of undetermined source (ESUS) who have atrial cardiopathy but no overt atrial fibrillation, suggest findings from the ARCADIA trial.

The trial, which was halted early, randomized more than 1,000 ESUS patients with atrial cardiomyopathy to apixaban or placebo. Results showed that apixaban did not improve rates of recurrent stroke of any kind nor safety outcomes such as major hemorrhage and all-cause mortality.

The results were presented at the annual meeting of the European Stroke Organisation Conference.

“We found no benefit of apixaban over aspirin in patients with ESUS who had evidence of atrial cardiopathy, at least based on the criteria in our trial,” said study presenter Hooman Kamel, MD, MS, vice chair for research and chief of neurocritical care in the department of neurology, Weill Cornell Medicine, New York.

“It could be that this concept of thrombogenic atrial cardiopathy really isn’t present unless there is also atrial fibrillation,” he continued, suggesting alternatively that results may be caused by the “incorrect choice of atrial cardiopathy biomarkers or thresholds.”

“We chose these because they were clinically scalable and usable in a multicenter design,” Dr. Kamel explained, adding that there are a number of different proposed biomarkers that could be used in a future study.

The team will now perform secondary analyses over the coming months to “try to help sort out some of these potential explanations.”

Dr. Kamel concluded, however, that, “as of now, no strategy of anticoagulation has been found to be better than antiplatelet therapy for secondary stroke prevention after ESUS.”
 

Similar results

Approached for comment, session cochair Robin Lemmens, MD, PhD, a neurologist in the department of neurosciences, UZ Leuven (Belgium), noted that this is the third ESUS trial, after the NAVIGATE and RE-SPECT trials, and they have all showed “similar results.”

He said, however, that there “could be various reasons for that, and it’s good that they mentioned looking into the subgroups,” as has been done for those other studies.

“Most of these trials were initiated under the concept that most of these patients would have had underlying atrial fibrillation, and then of course there would have been a benefit for anticoagulation.”

“It turns out that that’s not the case,” Dr. Lemmens said, “probably because there’s a lot of heterogeneity in these patients,” with different reasons for developing stroke, “not just only potentially underlying atrial fibrillation.”

Session cochair Arthur Liesz, MD, PhD, Institute for Stroke and Dementia Research, University Hospital, LMU Munich, added that it is important to consider the definition of atrial cardiopathy in this context.

If this was limited only to structural cardiopathy, then this “was a rather small subpopulation in this study,” he said in an interview.

Dr. Liesz said that it could instead have been conducted with “more stringent cutoffs,” and could have considered blood biomarkers, “which then would have delivered more overlap with structural cardiopathy,” and allowed those patients to be analyzed separately.
 

Heterogeneous etiologies?

Dr. Kamel began by noting that the failure of NAVIGATE and RESPECT to show a benefit from anticoagulation in the prevention of recurrent stroke in patients with ESUS led to the hypothesis that this is “perhaps due to heterogeneous underlying etiologies.”

Moreover, these etiologies “may require different types of antithrombotic therapy to best prevent recurrence, and one such underlying etiology may be atrial cardiopathy.”

He explained that several observational studies have found, in the absence of atrial fibrillation, associations between stroke and different markers of atrial cardiopathy and, “given the proven benefit of anticoagulation in preventing strokes in patients with atrial fibrillation, it seems plausible” that they may also benefit.

To investigate further, the team conducted ARCADIA, an investigator-initiated, multicenter, randomized trial involving patients aged 45 years and older from 185 sites in the United States and Canada with a clinical diagnosis of stroke that met the consensus criteria for ESUS.

They also were required to have undergone brain imaging to rule out hemorrhagic stroke, and to have a modified Rankin Scale score of 4 or less, indicating up to a moderately severe degree of disability.

They also had atrial cardiopathy, as determined by P-wave terminal force in V1 greater than 5,000mcV*ms on electrocardiography, serum N-terminal prohormone of brain natriuretic peptide levels greater than 250 pg/mL, or a left atrium diameter of at least 3 cm/m².

The patients were randomly assigned to apixaban 5 mg or 2.5 mg twice daily plus aspirin placebo, or apixaban placebo plus aspirin 81 mg daily. Those diagnosed with atrial fibrillation after randomization crossed over to open-label anticoagulant therapy at physician discretion.

Dr. Kamel reported that, in 2022, after enrollment of 1015 patients with a mean follow-up of 1.8 years, the trial was halted at the planned interim efficacy/futility analysis, adding that there were “no safety concerns.”

The apixaban and aspirin groups were well balanced in terms of their baseline characteristics. The mean age was 68 years, and 54% were female. Three-quarters of the participants were White; 21.1% were Black.

Prior stroke was reported in 19% of patients. Hypertension was common, in about 77%, and type 2 diabetes was seen in 31%. There were relatively few cases of ischemic heart disease, heart failure, and peripheral arterial disease.

The primary efficacy outcome of recurrent stroke of any type occurred in 4.4% of both patients treated with apixaban and those given aspirin, at a hazard ratio of 1.00 (95% confidence interval, 0.64-1.55). Similar findings were seen when looking individually at ischemic and hemorrhagic stroke, and stroke of undetermined type.

There was also no significant difference in the secondary outcomes of recurrent ischemic stroke or systemic embolism, at 4.1% versus 4.4% (HR, 0.92; 95% CI, 0.59-1.44), and recurrent stroke of any type or death from any cause, at 7.3% versus 6.8% (HR, 1.08; 95% CI, 0.76-1.52).

In terms of safety, rates of major hemorrhage were low and almost identical between the groups, at 0.7% with apixaban and 0.8% for aspirin (HR, 1.02; 95% CI, 0.29-3.51), and were similar for all-cause mortality, at 1.8% versus 1.2% (HR, 1.53; 95% CI, 0.63-3.74).

Proportionately more patients treated with aspirin experienced symptomatic intracranial hemorrhage, at 1.1% versus 0%.

The trial results generated a flurry of interest on Twitter.

Thomas Ford, MD, a vascular neurology fellow from Boston Medical Center, described the results as “disappointing,” although he was “curious to see if there was any signal of benefit in subgroup analyses.”

Shadi Yaghi, codirector of the Comprehensive Stroke Center at Brown University, Providence, R.I., added that the trial “begs the question [as to] whether all device-detected atrial fibrillation warrants anticoagulation.”

Replying, Mitchell Elkind, MD, MPhil, professor of neurology and epidemiology at Columbia University Irving Medical Center, New York, said that he agrees with this interpretation.

“Maybe the issue is not with the concept of atrial cardiopathy but with the need to [anticoagulate] all patients with low [atrial fibrillation] burden or incidental [atrial fibrillation] after stroke.”

The study was funded by the National Institutes of Health and the National Institute of Neurological Disorders and Stroke. The study drug was provided in kind by BMS-Pfizer, and ancillary funding for the NTproBNP assays was provided by Roche. No relevant financial relationships were reported.

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

MUNICH – Adding carotid revascularization to optimized medical therapy (OMT) does not appear to offer a clinical benefit in patients with significant carotid stenosis and a low to intermediate 5-year risk of stroke, suggests a planned interim analysis of ECST-2.

Almost 430 patients with symptomatic and asymptomatic atherosclerotic carotid stenosis greater than or equal to 50% and a Carotid Artery Risk (CAR) score less than 20% were randomly assigned to OMT alone or OMT plus revascularization with carotid endarterectomy (CEA) or carotid artery stenting.

The study, which was presented at the annual European Stroke Organisation Conference, was stopped early because of slow recruitment.

Nevertheless, the current results showed that there was no significant difference at 2 years between the treatment groups in the rate of a composite endpoint, as well as the occurrence of any stroke, myocardial infarction, and periprocedural death.

In other words, “there was no evidence of benefit at 2 years from additional carotid revascularization” in patients with carotid stenosis who had a low to intermediate predicted stroke risk, said study presenter Paul Nederkoorn, MD, PhD, department of neurology, Amsterdam UMC, University of Amsterdam.

He added, however, that the complete 2 years will include additional analyses, including an analysis of silent infarcts on MRI, which may affect the results, and that longer clinical follow-up is required.

Future work will include the design and validation of a novel stroke risk prediction tool that will include MRI plaque imaging and will allow individualized patient selection for revascularization, as well as a cost-effectiveness analysis, he noted.
 

Conclusions ‘difficult’

Session co-chair Peter Kelly, MD, professor of neurology at Mater University Hospital/University College Dublin, and president-elect of the European Stroke Association, described the findings as “interesting” and that it was “great to see them.”

“I’m sure we’ll be discussing these results for a while,” he added.

But co-chair Else Charlotte Sandset, MD, PhD, a consultant neurologist in the Stroke Unit, department of neurology, Oslo University Hospital, said that it’s “difficult to draw firm conclusions from the trial.”

The patients were highly selected, recruitment was “perhaps a bit too slow,” and the study was probably conducted over too many sites, she said in an interview.

Dr. Sandset also noted that the options available for OMT have changed over the course of the study, as well as the overall approach to management.

“We are more aware of how we should treat” these patients, and “we’re probably a bit more aggressive,” which will have shifted the outcomes in the comparator arm as the study progressed.

“That is the challenge of doing these trials that take many years to run – our practice changes.”
 

‘Old evidence’

In his presentation, Dr. Nederkoorn pointed out that, while the current guidelines for CEA are “robust,” they are based on “old evidence” from trials conducted 20-30 years ago.

During that time, he said, medical treatment has improved significantly, and the risk for stroke has approximately halved. Yet the decision to perform CEA is still largely based on the degree of stenosis and the patient’s symptom status.

Dr. Nederkoorn suggested, however, that factors such as plaque ulceration and patient characteristics and comorbidities might influence the risk-benefit ratio for revascularization.

The current trial was therefore established to test the hypothesis that patients with carotid stenosis greater than or equal to 50% and a low to intermediate risk of stroke will not benefit from additional carotid revascularization on top of optimized medical therapy.

The team conducted a prospective, multicenter, open clinical trial in which patients with both symptomatic and asymptomatic atherosclerotic carotid stenosis were randomly assigned to revascularization plus OMT or OMT alone.

Dr. Nederkoorn explained that a low to intermediate 5-year risk for stroke was established using the CAR score less than 20%.

This is based on a range of parameters, including the sex and age of the patient, degree of stenosis, the type of and time since the event, and the presence of comorbidities, among other factors.

He said that the data was originally derived from the NASCET trial, which was published in 1998, and the first ECST trial, published in the same year.

Since then, the risk of ipsilateral stroke has “strongly declined,” Dr. Nederkoorn said, and so the CAR score was recalibrated to reflect the likely benefit of current OMT.

For the trial, OMT included antihypertensive and cholesterol-lowering medications, and dietary changes, alongside antiplatelet agents and anticoagulation, if indicated, to achieve predefined, guideline-led lipid and blood pressure targets.

Revascularization included CEA and coronary artery stenting in selected patients and was recommended to be performed within 2 weeks of randomization in symptomatic patients and within 4 weeks in asymptomatic patients.

When the trial started in 2012, the intention was to recruit 2,000 patients, with a planned interim analysis after enrollment of 320 patients.

However, recruitment was suspended in 2019, with 429 patients having been enrolled, as it was clear that achieving a cohort of 2,000 patients was “not practical without a change in the trial design” to include MRI plaque imaging and without further funding.

Dr. Nederkoorn showed that the baseline characteristics of the OMT and revascularization plus OMT groups were comparable. The average age of the patients in the groups was 71-72 years, and 31% were female.

Symptomatic disease was present in about 40% of patients, and about 76% had hypertension. Type 2 diabetes was reported in roughly one-quarter of the patients.

There was no difference in the time from randomization to the revascularization procedure between patients with asymptomatic and symptomatic disease.

Moving to the primary outcome, which was a composite of periprocedural death within 90 days of randomization and clinically manifest stroke or myocardial infarction at 2 years, Dr. Nederkoorn showed that there was no significant difference between the treatment groups.

Despite a suggestion that patients undergoing revascularization experienced “more harm” in the initial follow-up period, particularly in patients with a CAR score greater than 10%, the event curves met at around 18 months.

Overall, the hazard ratio between revascularization plus OMT versus OMT alone was 0.96 (95% confidence interval, 0.53-1.76, P = .90).

Breaking down the composite endpoint, there was a numerically lower rate of any stroke with OMT alone, compared with revascularization plus OMT over the study period, but again the difference was not significant at 2 years, at a hazard ratio of 0.68 (95% CI, 0.32-1.42, P = .30).

There was only one case of periprocedural death, in the revascularization arm. Although myocardial infarction was numerically twice as likely with OMT alone, compared with the combined intervention arm, the difference was not significant, at a hazard ratio of 2.00 (95% CI, 0.68-5.84, P = .21).

The study was funded by the National Institute for Health and Care Research, the Swiss National Science Foundation, The Netherlands Organisation of Scientific Research, and the Leeds Neurology Foundation. No relevant financial relationships were declared.

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

MUNICH – Adding carotid revascularization to optimized medical therapy (OMT) does not appear to offer a clinical benefit in patients with significant carotid stenosis and a low to intermediate 5-year risk of stroke, suggests a planned interim analysis of ECST-2.

Almost 430 patients with symptomatic and asymptomatic atherosclerotic carotid stenosis greater than or equal to 50% and a Carotid Artery Risk (CAR) score less than 20% were randomly assigned to OMT alone or OMT plus revascularization with carotid endarterectomy (CEA) or carotid artery stenting.

The study, which was presented at the annual European Stroke Organisation Conference, was stopped early because of slow recruitment.

Nevertheless, the current results showed that there was no significant difference at 2 years between the treatment groups in the rate of a composite endpoint, as well as the occurrence of any stroke, myocardial infarction, and periprocedural death.

In other words, “there was no evidence of benefit at 2 years from additional carotid revascularization” in patients with carotid stenosis who had a low to intermediate predicted stroke risk, said study presenter Paul Nederkoorn, MD, PhD, department of neurology, Amsterdam UMC, University of Amsterdam.

He added, however, that the complete 2 years will include additional analyses, including an analysis of silent infarcts on MRI, which may affect the results, and that longer clinical follow-up is required.

Future work will include the design and validation of a novel stroke risk prediction tool that will include MRI plaque imaging and will allow individualized patient selection for revascularization, as well as a cost-effectiveness analysis, he noted.
 

Conclusions ‘difficult’

Session co-chair Peter Kelly, MD, professor of neurology at Mater University Hospital/University College Dublin, and president-elect of the European Stroke Association, described the findings as “interesting” and that it was “great to see them.”

“I’m sure we’ll be discussing these results for a while,” he added.

But co-chair Else Charlotte Sandset, MD, PhD, a consultant neurologist in the Stroke Unit, department of neurology, Oslo University Hospital, said that it’s “difficult to draw firm conclusions from the trial.”

The patients were highly selected, recruitment was “perhaps a bit too slow,” and the study was probably conducted over too many sites, she said in an interview.

Dr. Sandset also noted that the options available for OMT have changed over the course of the study, as well as the overall approach to management.

“We are more aware of how we should treat” these patients, and “we’re probably a bit more aggressive,” which will have shifted the outcomes in the comparator arm as the study progressed.

“That is the challenge of doing these trials that take many years to run – our practice changes.”
 

‘Old evidence’

In his presentation, Dr. Nederkoorn pointed out that, while the current guidelines for CEA are “robust,” they are based on “old evidence” from trials conducted 20-30 years ago.

During that time, he said, medical treatment has improved significantly, and the risk for stroke has approximately halved. Yet the decision to perform CEA is still largely based on the degree of stenosis and the patient’s symptom status.

Dr. Nederkoorn suggested, however, that factors such as plaque ulceration and patient characteristics and comorbidities might influence the risk-benefit ratio for revascularization.

The current trial was therefore established to test the hypothesis that patients with carotid stenosis greater than or equal to 50% and a low to intermediate risk of stroke will not benefit from additional carotid revascularization on top of optimized medical therapy.

The team conducted a prospective, multicenter, open clinical trial in which patients with both symptomatic and asymptomatic atherosclerotic carotid stenosis were randomly assigned to revascularization plus OMT or OMT alone.

Dr. Nederkoorn explained that a low to intermediate 5-year risk for stroke was established using the CAR score less than 20%.

This is based on a range of parameters, including the sex and age of the patient, degree of stenosis, the type of and time since the event, and the presence of comorbidities, among other factors.

He said that the data was originally derived from the NASCET trial, which was published in 1998, and the first ECST trial, published in the same year.

Since then, the risk of ipsilateral stroke has “strongly declined,” Dr. Nederkoorn said, and so the CAR score was recalibrated to reflect the likely benefit of current OMT.

For the trial, OMT included antihypertensive and cholesterol-lowering medications, and dietary changes, alongside antiplatelet agents and anticoagulation, if indicated, to achieve predefined, guideline-led lipid and blood pressure targets.

Revascularization included CEA and coronary artery stenting in selected patients and was recommended to be performed within 2 weeks of randomization in symptomatic patients and within 4 weeks in asymptomatic patients.

When the trial started in 2012, the intention was to recruit 2,000 patients, with a planned interim analysis after enrollment of 320 patients.

However, recruitment was suspended in 2019, with 429 patients having been enrolled, as it was clear that achieving a cohort of 2,000 patients was “not practical without a change in the trial design” to include MRI plaque imaging and without further funding.

Dr. Nederkoorn showed that the baseline characteristics of the OMT and revascularization plus OMT groups were comparable. The average age of the patients in the groups was 71-72 years, and 31% were female.

Symptomatic disease was present in about 40% of patients, and about 76% had hypertension. Type 2 diabetes was reported in roughly one-quarter of the patients.

There was no difference in the time from randomization to the revascularization procedure between patients with asymptomatic and symptomatic disease.

Moving to the primary outcome, which was a composite of periprocedural death within 90 days of randomization and clinically manifest stroke or myocardial infarction at 2 years, Dr. Nederkoorn showed that there was no significant difference between the treatment groups.

Despite a suggestion that patients undergoing revascularization experienced “more harm” in the initial follow-up period, particularly in patients with a CAR score greater than 10%, the event curves met at around 18 months.

Overall, the hazard ratio between revascularization plus OMT versus OMT alone was 0.96 (95% confidence interval, 0.53-1.76, P = .90).

Breaking down the composite endpoint, there was a numerically lower rate of any stroke with OMT alone, compared with revascularization plus OMT over the study period, but again the difference was not significant at 2 years, at a hazard ratio of 0.68 (95% CI, 0.32-1.42, P = .30).

There was only one case of periprocedural death, in the revascularization arm. Although myocardial infarction was numerically twice as likely with OMT alone, compared with the combined intervention arm, the difference was not significant, at a hazard ratio of 2.00 (95% CI, 0.68-5.84, P = .21).

The study was funded by the National Institute for Health and Care Research, the Swiss National Science Foundation, The Netherlands Organisation of Scientific Research, and the Leeds Neurology Foundation. No relevant financial relationships were declared.

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

MUNICH – Adding carotid revascularization to optimized medical therapy (OMT) does not appear to offer a clinical benefit in patients with significant carotid stenosis and a low to intermediate 5-year risk of stroke, suggests a planned interim analysis of ECST-2.

Almost 430 patients with symptomatic and asymptomatic atherosclerotic carotid stenosis greater than or equal to 50% and a Carotid Artery Risk (CAR) score less than 20% were randomly assigned to OMT alone or OMT plus revascularization with carotid endarterectomy (CEA) or carotid artery stenting.

The study, which was presented at the annual European Stroke Organisation Conference, was stopped early because of slow recruitment.

Nevertheless, the current results showed that there was no significant difference at 2 years between the treatment groups in the rate of a composite endpoint, as well as the occurrence of any stroke, myocardial infarction, and periprocedural death.

In other words, “there was no evidence of benefit at 2 years from additional carotid revascularization” in patients with carotid stenosis who had a low to intermediate predicted stroke risk, said study presenter Paul Nederkoorn, MD, PhD, department of neurology, Amsterdam UMC, University of Amsterdam.

He added, however, that the complete 2 years will include additional analyses, including an analysis of silent infarcts on MRI, which may affect the results, and that longer clinical follow-up is required.

Future work will include the design and validation of a novel stroke risk prediction tool that will include MRI plaque imaging and will allow individualized patient selection for revascularization, as well as a cost-effectiveness analysis, he noted.
 

Conclusions ‘difficult’

Session co-chair Peter Kelly, MD, professor of neurology at Mater University Hospital/University College Dublin, and president-elect of the European Stroke Association, described the findings as “interesting” and that it was “great to see them.”

“I’m sure we’ll be discussing these results for a while,” he added.

But co-chair Else Charlotte Sandset, MD, PhD, a consultant neurologist in the Stroke Unit, department of neurology, Oslo University Hospital, said that it’s “difficult to draw firm conclusions from the trial.”

The patients were highly selected, recruitment was “perhaps a bit too slow,” and the study was probably conducted over too many sites, she said in an interview.

Dr. Sandset also noted that the options available for OMT have changed over the course of the study, as well as the overall approach to management.

“We are more aware of how we should treat” these patients, and “we’re probably a bit more aggressive,” which will have shifted the outcomes in the comparator arm as the study progressed.

“That is the challenge of doing these trials that take many years to run – our practice changes.”
 

‘Old evidence’

In his presentation, Dr. Nederkoorn pointed out that, while the current guidelines for CEA are “robust,” they are based on “old evidence” from trials conducted 20-30 years ago.

During that time, he said, medical treatment has improved significantly, and the risk for stroke has approximately halved. Yet the decision to perform CEA is still largely based on the degree of stenosis and the patient’s symptom status.

Dr. Nederkoorn suggested, however, that factors such as plaque ulceration and patient characteristics and comorbidities might influence the risk-benefit ratio for revascularization.

The current trial was therefore established to test the hypothesis that patients with carotid stenosis greater than or equal to 50% and a low to intermediate risk of stroke will not benefit from additional carotid revascularization on top of optimized medical therapy.

The team conducted a prospective, multicenter, open clinical trial in which patients with both symptomatic and asymptomatic atherosclerotic carotid stenosis were randomly assigned to revascularization plus OMT or OMT alone.

Dr. Nederkoorn explained that a low to intermediate 5-year risk for stroke was established using the CAR score less than 20%.

This is based on a range of parameters, including the sex and age of the patient, degree of stenosis, the type of and time since the event, and the presence of comorbidities, among other factors.

He said that the data was originally derived from the NASCET trial, which was published in 1998, and the first ECST trial, published in the same year.

Since then, the risk of ipsilateral stroke has “strongly declined,” Dr. Nederkoorn said, and so the CAR score was recalibrated to reflect the likely benefit of current OMT.

For the trial, OMT included antihypertensive and cholesterol-lowering medications, and dietary changes, alongside antiplatelet agents and anticoagulation, if indicated, to achieve predefined, guideline-led lipid and blood pressure targets.

Revascularization included CEA and coronary artery stenting in selected patients and was recommended to be performed within 2 weeks of randomization in symptomatic patients and within 4 weeks in asymptomatic patients.

When the trial started in 2012, the intention was to recruit 2,000 patients, with a planned interim analysis after enrollment of 320 patients.

However, recruitment was suspended in 2019, with 429 patients having been enrolled, as it was clear that achieving a cohort of 2,000 patients was “not practical without a change in the trial design” to include MRI plaque imaging and without further funding.

Dr. Nederkoorn showed that the baseline characteristics of the OMT and revascularization plus OMT groups were comparable. The average age of the patients in the groups was 71-72 years, and 31% were female.

Symptomatic disease was present in about 40% of patients, and about 76% had hypertension. Type 2 diabetes was reported in roughly one-quarter of the patients.

There was no difference in the time from randomization to the revascularization procedure between patients with asymptomatic and symptomatic disease.

Moving to the primary outcome, which was a composite of periprocedural death within 90 days of randomization and clinically manifest stroke or myocardial infarction at 2 years, Dr. Nederkoorn showed that there was no significant difference between the treatment groups.

Despite a suggestion that patients undergoing revascularization experienced “more harm” in the initial follow-up period, particularly in patients with a CAR score greater than 10%, the event curves met at around 18 months.

Overall, the hazard ratio between revascularization plus OMT versus OMT alone was 0.96 (95% confidence interval, 0.53-1.76, P = .90).

Breaking down the composite endpoint, there was a numerically lower rate of any stroke with OMT alone, compared with revascularization plus OMT over the study period, but again the difference was not significant at 2 years, at a hazard ratio of 0.68 (95% CI, 0.32-1.42, P = .30).

There was only one case of periprocedural death, in the revascularization arm. Although myocardial infarction was numerically twice as likely with OMT alone, compared with the combined intervention arm, the difference was not significant, at a hazard ratio of 2.00 (95% CI, 0.68-5.84, P = .21).

The study was funded by the National Institute for Health and Care Research, the Swiss National Science Foundation, The Netherlands Organisation of Scientific Research, and the Leeds Neurology Foundation. No relevant financial relationships were declared.

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

In response to a randomized trial that associated elective revascularization for ischemia with an increase in noncardiac mortality versus medical therapy alone, a meta-analysis with a far larger dataset challenges this assertion, suggesting the initial conclusion is due to a type 1 error. 

With data from nearly 17,000 patients in 18 randomized trials, the meta-analysis showed no signal for increased noncardiac mortality in the revascularization group overall or across several sensitivity analyses, reports William Wijns, MD, PhD, professor of interventional cardiology, National University of Ireland, Galway.

The larger pool of data from the meta-analysis was considered compelling by several experts at the annual meeting of the European Association of Percutaneous Cardiovascular Interventions, where it was presented.

“I think these data will close once and forever this controversy,” said Davide Capodanno, MD, PhD, a professor of cardiology and interventional cardiologist at the University of Catania (Italy). 

Evidence for an unexpected increased risk of noncardiac mortality was drawn from the ISCHEMIA-EXTEND study, which was published earlier this year. Numerous prior studies comparing percutaneous intervention (PCI) to medical therapy for relief of ischemia had shown no such safety signal. 

The ISCHEMIA-EXTEND study provided long-term follow up of patients enrolled in ISCHEMIA, a study that randomized patients with stable coronary disease and moderate or severe ischemia to PCI or a conservative approach. After 3.2 years of follow up, there was no reduction in risk of cardiovascular events or all-cause death. While this lack of benefit was a disappointing result from the perspective of interventional cardiology, there was also no increase in these risks. 

In ISCHEMIA-EXTEND, the more than 5,000 patients originally randomized were followed for an additional 2.5 years (total 5.7 years). During this extended period, the estimated 7-year risk of cardiovascular mortality was 22% lower in the group randomized to PCI (hazard ratio, 0.78; 95% confidence interval, 0.63-0.96) but the noncardiac mortality was increased by 44% (HR, 1.44; 95% CI, 1.08-1.91). Because of the counterbalancing effects on survival, all-cause mortality was similar in the two groups.

The newly completed meta-analysis was undertaken to address this surprising result not least because the increased rates of noncardiac death did not have a plausible explanation, according to Dr. Wijns. 

When the patients from the 18 randomized trials were compared, noncardiac death occurred in 4.68% of the 8,665 patients assigned to elective revascularization and in 4.17% of the 8,243 patients assigned to medical therapy alone at an average follow up of 5.7 years. 

This difference was not significant overall (HR, 1.09; 95% CI, 0.94-1.26; P = .26) or after sensitivity analyses. For example, there was no difference (P = .52) between an invasive or conservative approach after controlling for length of follow up. 

There was also no heterogeneity (I2 = 0%) among the studies when ISCHEMIA-EXTEND was excluded.
 

Absence of negative effect ‘is confirmed’

On the basis of a Bayesian meta-analysis designed to account for residual uncertainty (relative risk, 1.08, 95% CI, 0.90-1.30) and the consistency of results among all studies with the exception of ISCHEMIA-EXTEND (RR, 1.0; 95% CI, 0.84-1;18; P = .7), “the absence of a negative effect of revascularization on noncardiac death was confirmed,” Dr. Wijns reported. 

Based on the preponderance of evidence assembled in this meta-analysis, the “noncardiac mortality excess risk observed following revascularization relative to medical therapy was confined to a single large trial and is likely due to a type 1 error,” Dr. Wijns reported. He noted that this study is “the first large-scale meta-analysis study designed to systematically evaluate potential differences in noncardiac mortality between treatment strategies for chronic coronary syndromes.” 

Eliano P. Navarese, MD, PhD, an associate professor of interventional cardiology at Nicolaus Copernicus University, Bydgoszcz, Poland, was the lead author of this study and Dr. Wijns was a coinvestigator. The study was published simultaneously in the Journal of the American College of Cardiology at the time of the EuroPCR meeting.

In the late-breaking session where these data were presented, there was a general consensus among invited panelists that the data are convincing. For example, Michael Joner, MD, PhD, director of early clinical trials, German Heart Centre, Munich, agreed that these data “resolve the issue.” 

Bernard de Bruyne, MD, PhD, an interventional cardiologist associated with the Cardiovascular Center Aalst, Kraainem, Belgium, also agreed that these data argue convincingly against the concern raised by publication of ISCHEMIA-EXTEND, but he added that this controversy has raised an important issue.

“We should always be reporting all-cause mortality, not just cardiovascular mortality, in our clinical trials,” he said, emphasizing that extending all-cause survival, not just preventing cardiovascular-related events, should be recognized as the goal of invasive strategies.

In an editorial accompanying the publication, Dr. Harvey D. White, MD, Te Whatu Ora-Health New Zealand, Auckland, writes similarly that the current findings, “alert us to the importance of adjudicating causes of death in clinical trials. 

“The current trial-level meta-analysis may seem to dispel concerns about increases in noncardiac and cardiovascular deaths seen in some revascularization trials, but paradoxically, it has raised the need for more and careful analysis of causes of death,” Dr. White notes. He feels the signal of increased noncardiac or noncardiovascular death in ISCHEMIA EXTEND and the REVIVED trials is something “that we should pay attention to and explore the possibility that increased radiation doses with PCI may cause increased rates of cancer.” 

Further study, including longer follow-up, other datasets, and quality of life data including cognitive function and “patient-focused outcomes such as day alive out of hospital,” is needed, he concludes. 

Dr. Navarese has received research grants from Abbott and Amgen and lecture fees/honoraria from Amgen, AstraZeneca, Bayer, Pfizer, and Sanofi-Regeneron. Dr. Wijns reports financial relationships with Argonauts, Corrib Core Laboratory, and Rede Optimus Research. Dr. Capodanno reports financial relationships with Amgen, Daiichi Sankyo, and Sanofi. Dr. de Bruyne and Dr. Joner report financial relationships with multiple pharmaceutical and device manufacturers. Prof. White, as the John Neutze scholar, is supported by the Green Lane Research and Educational Fund. Prof. White has received grant support paid to the institution and fees for serving on steering committees of multiple trials sponsored by various companies.
 

In response to a randomized trial that associated elective revascularization for ischemia with an increase in noncardiac mortality versus medical therapy alone, a meta-analysis with a far larger dataset challenges this assertion, suggesting the initial conclusion is due to a type 1 error. 

With data from nearly 17,000 patients in 18 randomized trials, the meta-analysis showed no signal for increased noncardiac mortality in the revascularization group overall or across several sensitivity analyses, reports William Wijns, MD, PhD, professor of interventional cardiology, National University of Ireland, Galway.

The larger pool of data from the meta-analysis was considered compelling by several experts at the annual meeting of the European Association of Percutaneous Cardiovascular Interventions, where it was presented.

“I think these data will close once and forever this controversy,” said Davide Capodanno, MD, PhD, a professor of cardiology and interventional cardiologist at the University of Catania (Italy). 

Evidence for an unexpected increased risk of noncardiac mortality was drawn from the ISCHEMIA-EXTEND study, which was published earlier this year. Numerous prior studies comparing percutaneous intervention (PCI) to medical therapy for relief of ischemia had shown no such safety signal. 

The ISCHEMIA-EXTEND study provided long-term follow up of patients enrolled in ISCHEMIA, a study that randomized patients with stable coronary disease and moderate or severe ischemia to PCI or a conservative approach. After 3.2 years of follow up, there was no reduction in risk of cardiovascular events or all-cause death. While this lack of benefit was a disappointing result from the perspective of interventional cardiology, there was also no increase in these risks. 

In ISCHEMIA-EXTEND, the more than 5,000 patients originally randomized were followed for an additional 2.5 years (total 5.7 years). During this extended period, the estimated 7-year risk of cardiovascular mortality was 22% lower in the group randomized to PCI (hazard ratio, 0.78; 95% confidence interval, 0.63-0.96) but the noncardiac mortality was increased by 44% (HR, 1.44; 95% CI, 1.08-1.91). Because of the counterbalancing effects on survival, all-cause mortality was similar in the two groups.

The newly completed meta-analysis was undertaken to address this surprising result not least because the increased rates of noncardiac death did not have a plausible explanation, according to Dr. Wijns. 

When the patients from the 18 randomized trials were compared, noncardiac death occurred in 4.68% of the 8,665 patients assigned to elective revascularization and in 4.17% of the 8,243 patients assigned to medical therapy alone at an average follow up of 5.7 years. 

This difference was not significant overall (HR, 1.09; 95% CI, 0.94-1.26; P = .26) or after sensitivity analyses. For example, there was no difference (P = .52) between an invasive or conservative approach after controlling for length of follow up. 

There was also no heterogeneity (I2 = 0%) among the studies when ISCHEMIA-EXTEND was excluded.
 

Absence of negative effect ‘is confirmed’

On the basis of a Bayesian meta-analysis designed to account for residual uncertainty (relative risk, 1.08, 95% CI, 0.90-1.30) and the consistency of results among all studies with the exception of ISCHEMIA-EXTEND (RR, 1.0; 95% CI, 0.84-1;18; P = .7), “the absence of a negative effect of revascularization on noncardiac death was confirmed,” Dr. Wijns reported. 

Based on the preponderance of evidence assembled in this meta-analysis, the “noncardiac mortality excess risk observed following revascularization relative to medical therapy was confined to a single large trial and is likely due to a type 1 error,” Dr. Wijns reported. He noted that this study is “the first large-scale meta-analysis study designed to systematically evaluate potential differences in noncardiac mortality between treatment strategies for chronic coronary syndromes.” 

Eliano P. Navarese, MD, PhD, an associate professor of interventional cardiology at Nicolaus Copernicus University, Bydgoszcz, Poland, was the lead author of this study and Dr. Wijns was a coinvestigator. The study was published simultaneously in the Journal of the American College of Cardiology at the time of the EuroPCR meeting.

In the late-breaking session where these data were presented, there was a general consensus among invited panelists that the data are convincing. For example, Michael Joner, MD, PhD, director of early clinical trials, German Heart Centre, Munich, agreed that these data “resolve the issue.” 

Bernard de Bruyne, MD, PhD, an interventional cardiologist associated with the Cardiovascular Center Aalst, Kraainem, Belgium, also agreed that these data argue convincingly against the concern raised by publication of ISCHEMIA-EXTEND, but he added that this controversy has raised an important issue.

“We should always be reporting all-cause mortality, not just cardiovascular mortality, in our clinical trials,” he said, emphasizing that extending all-cause survival, not just preventing cardiovascular-related events, should be recognized as the goal of invasive strategies.

In an editorial accompanying the publication, Dr. Harvey D. White, MD, Te Whatu Ora-Health New Zealand, Auckland, writes similarly that the current findings, “alert us to the importance of adjudicating causes of death in clinical trials. 

“The current trial-level meta-analysis may seem to dispel concerns about increases in noncardiac and cardiovascular deaths seen in some revascularization trials, but paradoxically, it has raised the need for more and careful analysis of causes of death,” Dr. White notes. He feels the signal of increased noncardiac or noncardiovascular death in ISCHEMIA EXTEND and the REVIVED trials is something “that we should pay attention to and explore the possibility that increased radiation doses with PCI may cause increased rates of cancer.” 

Further study, including longer follow-up, other datasets, and quality of life data including cognitive function and “patient-focused outcomes such as day alive out of hospital,” is needed, he concludes. 

Dr. Navarese has received research grants from Abbott and Amgen and lecture fees/honoraria from Amgen, AstraZeneca, Bayer, Pfizer, and Sanofi-Regeneron. Dr. Wijns reports financial relationships with Argonauts, Corrib Core Laboratory, and Rede Optimus Research. Dr. Capodanno reports financial relationships with Amgen, Daiichi Sankyo, and Sanofi. Dr. de Bruyne and Dr. Joner report financial relationships with multiple pharmaceutical and device manufacturers. Prof. White, as the John Neutze scholar, is supported by the Green Lane Research and Educational Fund. Prof. White has received grant support paid to the institution and fees for serving on steering committees of multiple trials sponsored by various companies.
 

In response to a randomized trial that associated elective revascularization for ischemia with an increase in noncardiac mortality versus medical therapy alone, a meta-analysis with a far larger dataset challenges this assertion, suggesting the initial conclusion is due to a type 1 error. 

With data from nearly 17,000 patients in 18 randomized trials, the meta-analysis showed no signal for increased noncardiac mortality in the revascularization group overall or across several sensitivity analyses, reports William Wijns, MD, PhD, professor of interventional cardiology, National University of Ireland, Galway.

The larger pool of data from the meta-analysis was considered compelling by several experts at the annual meeting of the European Association of Percutaneous Cardiovascular Interventions, where it was presented.

“I think these data will close once and forever this controversy,” said Davide Capodanno, MD, PhD, a professor of cardiology and interventional cardiologist at the University of Catania (Italy). 

Evidence for an unexpected increased risk of noncardiac mortality was drawn from the ISCHEMIA-EXTEND study, which was published earlier this year. Numerous prior studies comparing percutaneous intervention (PCI) to medical therapy for relief of ischemia had shown no such safety signal. 

The ISCHEMIA-EXTEND study provided long-term follow up of patients enrolled in ISCHEMIA, a study that randomized patients with stable coronary disease and moderate or severe ischemia to PCI or a conservative approach. After 3.2 years of follow up, there was no reduction in risk of cardiovascular events or all-cause death. While this lack of benefit was a disappointing result from the perspective of interventional cardiology, there was also no increase in these risks. 

In ISCHEMIA-EXTEND, the more than 5,000 patients originally randomized were followed for an additional 2.5 years (total 5.7 years). During this extended period, the estimated 7-year risk of cardiovascular mortality was 22% lower in the group randomized to PCI (hazard ratio, 0.78; 95% confidence interval, 0.63-0.96) but the noncardiac mortality was increased by 44% (HR, 1.44; 95% CI, 1.08-1.91). Because of the counterbalancing effects on survival, all-cause mortality was similar in the two groups.

The newly completed meta-analysis was undertaken to address this surprising result not least because the increased rates of noncardiac death did not have a plausible explanation, according to Dr. Wijns. 

When the patients from the 18 randomized trials were compared, noncardiac death occurred in 4.68% of the 8,665 patients assigned to elective revascularization and in 4.17% of the 8,243 patients assigned to medical therapy alone at an average follow up of 5.7 years. 

This difference was not significant overall (HR, 1.09; 95% CI, 0.94-1.26; P = .26) or after sensitivity analyses. For example, there was no difference (P = .52) between an invasive or conservative approach after controlling for length of follow up. 

There was also no heterogeneity (I2 = 0%) among the studies when ISCHEMIA-EXTEND was excluded.
 

Absence of negative effect ‘is confirmed’

On the basis of a Bayesian meta-analysis designed to account for residual uncertainty (relative risk, 1.08, 95% CI, 0.90-1.30) and the consistency of results among all studies with the exception of ISCHEMIA-EXTEND (RR, 1.0; 95% CI, 0.84-1;18; P = .7), “the absence of a negative effect of revascularization on noncardiac death was confirmed,” Dr. Wijns reported. 

Based on the preponderance of evidence assembled in this meta-analysis, the “noncardiac mortality excess risk observed following revascularization relative to medical therapy was confined to a single large trial and is likely due to a type 1 error,” Dr. Wijns reported. He noted that this study is “the first large-scale meta-analysis study designed to systematically evaluate potential differences in noncardiac mortality between treatment strategies for chronic coronary syndromes.” 

Eliano P. Navarese, MD, PhD, an associate professor of interventional cardiology at Nicolaus Copernicus University, Bydgoszcz, Poland, was the lead author of this study and Dr. Wijns was a coinvestigator. The study was published simultaneously in the Journal of the American College of Cardiology at the time of the EuroPCR meeting.

In the late-breaking session where these data were presented, there was a general consensus among invited panelists that the data are convincing. For example, Michael Joner, MD, PhD, director of early clinical trials, German Heart Centre, Munich, agreed that these data “resolve the issue.” 

Bernard de Bruyne, MD, PhD, an interventional cardiologist associated with the Cardiovascular Center Aalst, Kraainem, Belgium, also agreed that these data argue convincingly against the concern raised by publication of ISCHEMIA-EXTEND, but he added that this controversy has raised an important issue.

“We should always be reporting all-cause mortality, not just cardiovascular mortality, in our clinical trials,” he said, emphasizing that extending all-cause survival, not just preventing cardiovascular-related events, should be recognized as the goal of invasive strategies.

In an editorial accompanying the publication, Dr. Harvey D. White, MD, Te Whatu Ora-Health New Zealand, Auckland, writes similarly that the current findings, “alert us to the importance of adjudicating causes of death in clinical trials. 

“The current trial-level meta-analysis may seem to dispel concerns about increases in noncardiac and cardiovascular deaths seen in some revascularization trials, but paradoxically, it has raised the need for more and careful analysis of causes of death,” Dr. White notes. He feels the signal of increased noncardiac or noncardiovascular death in ISCHEMIA EXTEND and the REVIVED trials is something “that we should pay attention to and explore the possibility that increased radiation doses with PCI may cause increased rates of cancer.” 

Further study, including longer follow-up, other datasets, and quality of life data including cognitive function and “patient-focused outcomes such as day alive out of hospital,” is needed, he concludes. 

Dr. Navarese has received research grants from Abbott and Amgen and lecture fees/honoraria from Amgen, AstraZeneca, Bayer, Pfizer, and Sanofi-Regeneron. Dr. Wijns reports financial relationships with Argonauts, Corrib Core Laboratory, and Rede Optimus Research. Dr. Capodanno reports financial relationships with Amgen, Daiichi Sankyo, and Sanofi. Dr. de Bruyne and Dr. Joner report financial relationships with multiple pharmaceutical and device manufacturers. Prof. White, as the John Neutze scholar, is supported by the Green Lane Research and Educational Fund. Prof. White has received grant support paid to the institution and fees for serving on steering committees of multiple trials sponsored by various companies.
 

Stress-related disorders and anxiety are associated with a higher risk of out-of-hospital cardiac arrest (OHCA), a new case-control study suggests.

Investigators compared more than 35,000 OHCA case patients with a similar number of matched control persons and found an almost 1.5 times higher hazard of long-term stress conditions among OHCA case patients, compared with control persons, with a similar hazard for anxiety. Posttraumatic stress disorder was associated with an almost twofold higher risk of OHCA.

The findings applied equally to men and women and were independent of the presence of cardiovascular disease (CVD).

“This study raises awareness of the higher risks of OHCA and early risk monitoring to prevent OHCA in patients with stress-related disorders and anxiety,” write Talip Eroglu, of the department of cardiology, Copenhagen University Hospital, and colleagues.

The study was published online  in BMJ Open Heart.
 

Stress disorders and anxiety overrepresented

OHCA “predominantly arises from lethal cardiac arrhythmias ... that occur most frequently in the setting of coronary heart disease,” the authors write. However, increasing evidence suggests that rates of OHCA may also be increased in association with noncardiac diseases.

Individuals with stress-related disorders and anxiety are “overrepresented” among victims of cardiac arrest as well as those with multiple CVDs. But previous studies of OHCA have been limited by small numbers of cardiac arrests. In addition, those studies involved only data from selected populations or used in-hospital diagnosis to identify cardiac arrest, thereby potentially omitting OHCA patients who died prior to hospital admission.

The researchers therefore turned to data from Danish health registries that include a large, unselected cohort of patients with OHCA to investigate whether long-term stress conditions (that is, PTSD and adjustment disorder) or anxiety disorder were associated with OHCA.

They stratified the cohort according to sex, age, and CVD to identify which risk factor confers the highest risk of OHCA in patients with long-term stress conditions or anxiety, and they conducted sensitivity analyses of potential confounders, such as depression.

The design was a nested-case control model in which records at an individual patient level across registries were cross-linked to data from other national registries and were compared to matched control persons from the general population (35,195 OHCAs and 351,950 matched control persons; median IQR age, 72 [62-81] years; 66.82% men).

The prevalence of comorbidities and use of cardiovascular drugs were higher among OHCA case patients than among non-OHCA control persons.
 

Keep aware of stress and anxiety as risk factors

Among OHCA and non-OHCA participants, long-term stress conditions were diagnosed in 0.92% and 0.45%, respectively. Anxiety was diagnosed in 0.85% of OHCA case patients and in 0.37% of non-OHCA control persons.

These conditions were associated with a higher rate of OHCA after adjustment for common OHCA risk factors.

Detrimental to the heart, not just the psyche

Glenn Levine, MD, master clinician and professor of medicine, Baylor College of Medicine, Houston, called it an “important study in that it is a large, nationwide cohort study and thus provides important information to complement much smaller, focused studies.”

Like those other studies, “it finds that negative psychological health, specifically, long-term stress (as well as anxiety), is associated with a significantly increased risk of out-of-hospital cardiac arrest,” continued Dr. Levine, who is the chief of the cardiology section at Michael E. DeBakey VA Medical Center, Houston, and was not involved with the study.

Dr. Levine thinks the study “does a good job, as best one can for such a study, in trying to control for other factors, and zeroing in specifically on stress (and anxiety), trying to assess their independent contributions to the risk of developing cardiac arrest.”

The take-home message for clinicians and patients “is that negative psychological stress factors, such as stress and anxiety, are not only detrimental to one’s psychological health but likely increase one’s risk for adverse cardiac events, such as cardiac arrest,” he stated.

No specific funding for the study was disclosed. Mr. Eroglu has disclosed no relevant financial relationships. The other authors’ disclosures are listed in the original article. Dr. Levine reports no relevant financial relationships.

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

Stress-related disorders and anxiety are associated with a higher risk of out-of-hospital cardiac arrest (OHCA), a new case-control study suggests.

Investigators compared more than 35,000 OHCA case patients with a similar number of matched control persons and found an almost 1.5 times higher hazard of long-term stress conditions among OHCA case patients, compared with control persons, with a similar hazard for anxiety. Posttraumatic stress disorder was associated with an almost twofold higher risk of OHCA.

The findings applied equally to men and women and were independent of the presence of cardiovascular disease (CVD).

“This study raises awareness of the higher risks of OHCA and early risk monitoring to prevent OHCA in patients with stress-related disorders and anxiety,” write Talip Eroglu, of the department of cardiology, Copenhagen University Hospital, and colleagues.

The study was published online  in BMJ Open Heart.
 

Stress disorders and anxiety overrepresented

OHCA “predominantly arises from lethal cardiac arrhythmias ... that occur most frequently in the setting of coronary heart disease,” the authors write. However, increasing evidence suggests that rates of OHCA may also be increased in association with noncardiac diseases.

Individuals with stress-related disorders and anxiety are “overrepresented” among victims of cardiac arrest as well as those with multiple CVDs. But previous studies of OHCA have been limited by small numbers of cardiac arrests. In addition, those studies involved only data from selected populations or used in-hospital diagnosis to identify cardiac arrest, thereby potentially omitting OHCA patients who died prior to hospital admission.

The researchers therefore turned to data from Danish health registries that include a large, unselected cohort of patients with OHCA to investigate whether long-term stress conditions (that is, PTSD and adjustment disorder) or anxiety disorder were associated with OHCA.

They stratified the cohort according to sex, age, and CVD to identify which risk factor confers the highest risk of OHCA in patients with long-term stress conditions or anxiety, and they conducted sensitivity analyses of potential confounders, such as depression.

The design was a nested-case control model in which records at an individual patient level across registries were cross-linked to data from other national registries and were compared to matched control persons from the general population (35,195 OHCAs and 351,950 matched control persons; median IQR age, 72 [62-81] years; 66.82% men).

The prevalence of comorbidities and use of cardiovascular drugs were higher among OHCA case patients than among non-OHCA control persons.
 

Keep aware of stress and anxiety as risk factors

Among OHCA and non-OHCA participants, long-term stress conditions were diagnosed in 0.92% and 0.45%, respectively. Anxiety was diagnosed in 0.85% of OHCA case patients and in 0.37% of non-OHCA control persons.

These conditions were associated with a higher rate of OHCA after adjustment for common OHCA risk factors.

Detrimental to the heart, not just the psyche

Glenn Levine, MD, master clinician and professor of medicine, Baylor College of Medicine, Houston, called it an “important study in that it is a large, nationwide cohort study and thus provides important information to complement much smaller, focused studies.”

Like those other studies, “it finds that negative psychological health, specifically, long-term stress (as well as anxiety), is associated with a significantly increased risk of out-of-hospital cardiac arrest,” continued Dr. Levine, who is the chief of the cardiology section at Michael E. DeBakey VA Medical Center, Houston, and was not involved with the study.

Dr. Levine thinks the study “does a good job, as best one can for such a study, in trying to control for other factors, and zeroing in specifically on stress (and anxiety), trying to assess their independent contributions to the risk of developing cardiac arrest.”

The take-home message for clinicians and patients “is that negative psychological stress factors, such as stress and anxiety, are not only detrimental to one’s psychological health but likely increase one’s risk for adverse cardiac events, such as cardiac arrest,” he stated.

No specific funding for the study was disclosed. Mr. Eroglu has disclosed no relevant financial relationships. The other authors’ disclosures are listed in the original article. Dr. Levine reports no relevant financial relationships.

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

Stress-related disorders and anxiety are associated with a higher risk of out-of-hospital cardiac arrest (OHCA), a new case-control study suggests.

Investigators compared more than 35,000 OHCA case patients with a similar number of matched control persons and found an almost 1.5 times higher hazard of long-term stress conditions among OHCA case patients, compared with control persons, with a similar hazard for anxiety. Posttraumatic stress disorder was associated with an almost twofold higher risk of OHCA.

The findings applied equally to men and women and were independent of the presence of cardiovascular disease (CVD).

“This study raises awareness of the higher risks of OHCA and early risk monitoring to prevent OHCA in patients with stress-related disorders and anxiety,” write Talip Eroglu, of the department of cardiology, Copenhagen University Hospital, and colleagues.

The study was published online  in BMJ Open Heart.
 

Stress disorders and anxiety overrepresented

OHCA “predominantly arises from lethal cardiac arrhythmias ... that occur most frequently in the setting of coronary heart disease,” the authors write. However, increasing evidence suggests that rates of OHCA may also be increased in association with noncardiac diseases.

Individuals with stress-related disorders and anxiety are “overrepresented” among victims of cardiac arrest as well as those with multiple CVDs. But previous studies of OHCA have been limited by small numbers of cardiac arrests. In addition, those studies involved only data from selected populations or used in-hospital diagnosis to identify cardiac arrest, thereby potentially omitting OHCA patients who died prior to hospital admission.

The researchers therefore turned to data from Danish health registries that include a large, unselected cohort of patients with OHCA to investigate whether long-term stress conditions (that is, PTSD and adjustment disorder) or anxiety disorder were associated with OHCA.

They stratified the cohort according to sex, age, and CVD to identify which risk factor confers the highest risk of OHCA in patients with long-term stress conditions or anxiety, and they conducted sensitivity analyses of potential confounders, such as depression.

The design was a nested-case control model in which records at an individual patient level across registries were cross-linked to data from other national registries and were compared to matched control persons from the general population (35,195 OHCAs and 351,950 matched control persons; median IQR age, 72 [62-81] years; 66.82% men).

The prevalence of comorbidities and use of cardiovascular drugs were higher among OHCA case patients than among non-OHCA control persons.
 

Keep aware of stress and anxiety as risk factors

Among OHCA and non-OHCA participants, long-term stress conditions were diagnosed in 0.92% and 0.45%, respectively. Anxiety was diagnosed in 0.85% of OHCA case patients and in 0.37% of non-OHCA control persons.

These conditions were associated with a higher rate of OHCA after adjustment for common OHCA risk factors.

Detrimental to the heart, not just the psyche

Glenn Levine, MD, master clinician and professor of medicine, Baylor College of Medicine, Houston, called it an “important study in that it is a large, nationwide cohort study and thus provides important information to complement much smaller, focused studies.”

Like those other studies, “it finds that negative psychological health, specifically, long-term stress (as well as anxiety), is associated with a significantly increased risk of out-of-hospital cardiac arrest,” continued Dr. Levine, who is the chief of the cardiology section at Michael E. DeBakey VA Medical Center, Houston, and was not involved with the study.

Dr. Levine thinks the study “does a good job, as best one can for such a study, in trying to control for other factors, and zeroing in specifically on stress (and anxiety), trying to assess their independent contributions to the risk of developing cardiac arrest.”

The take-home message for clinicians and patients “is that negative psychological stress factors, such as stress and anxiety, are not only detrimental to one’s psychological health but likely increase one’s risk for adverse cardiac events, such as cardiac arrest,” he stated.

No specific funding for the study was disclosed. Mr. Eroglu has disclosed no relevant financial relationships. The other authors’ disclosures are listed in the original article. Dr. Levine reports no relevant financial relationships.

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

Sotagliflozin, a novel agent that inhibits sodium-glucose cotransporter 1 as well as SGLT2, has received marketing approval from the Food and Drug Administration for reducing the risk for cardiovascular death, hospitalization for heart failure, and urgent heart failure visits in patients with heart failure, and also for preventing these same events in patients with type 2 diabetes, chronic kidney disease (CKD), and other cardiovascular disease risk factors.

This puts sotagliflozin in direct competition with two SGLT2 inhibitors, dapagliflozin (Farxiga) and empagliflozin (Jardiance), that already have indications for preventing heart failure hospitalizations in patients with heart failure as well as approvals for type 2 diabetes and preservation of renal function.

Officials at Lexicon Pharmaceuticals, the company that developed and will market sotagliflozin under the trade name Inpefa, said in a press release that they expect U.S. sales of the agent to begin before the end of June 2023. The release also highlighted that the approval broadly covered use in patients with heart failure across the full range of both reduced and preserved left ventricular ejection fractions.

Lexicon officials also said that the company will focus on marketing sotagliflozin for preventing near-term rehospitalizations of patients discharged after an episode of acute heart failure decompensation.

They base this niche target for sotagliflozin on results from the SOLOIST-WHF trial, which randomized 1,222 patients with type 2 diabetes recently hospitalized for worsening heart failure and showed a significant 33% reduction in the rate of deaths from cardiovascular causes and hospitalizations and urgent visits for heart failure, compared with control patients during a median 9 months of follow-up. Nearly half of the enrolled patients received their first dose while still hospitalized, while the other half received their first dose a median of 2 days after hospital discharge. The drug appeared safe.
 

Cutting heart failure rehospitalizations in half

An exploratory post hoc analysis of SOLOIST-WHF showed that treatment with sotagliflozin cut the rate of rehospitalizations roughly in half after both 30 and 90 days compared with control patients, according to an abstract presented at the 2022 annual scientific sessions of the AHA that has not yet been published in a peer-reviewed journal.

The only SGLT2 inhibitor tested so far when initiated in patients during hospitalization for heart failure is empagliflozin, in the EMPULSE trial, which randomized 530 patients. EMPULSE also showed that starting an SGLT2 inhibitor in this setting was safe and resulted in significant clinical benefit, the study’s primary endpoint, defined as a composite of death from any cause, number of heart failure events, and time to first heart failure event, or a 5-point or greater difference in change from baseline in the Kansas City Cardiomyopathy Questionnaire Total Symptom Score at 90 days.

In the DELIVER trial, which tested dapagliflozin in patients with heart failure with preserved ejection fraction, roughly 10% of patients started study treatment during or within 30 days of heart failure hospitalization, and in this subgroup, dapagliflozin appeared as effective as it was in the other 90% of patients who did not start the drug during an acute or subacute phase.

Despite the SOLOIST-WHF evidence for sotagliflozin’s safety and efficacy in this economically important clinical setting, some experts say the drug faces an uphill path as it contends for market share against two solidly established, albeit dramatically underused, SGLT2 inhibitors. (Recent data document that 20% or fewer of U.S. patients eligible for treatment with an SGLT2 inhibitor receive it, such as a review of 49,000 patients hospitalized during 2021-2022 with heart failure with reduced ejection fraction.)

Others foresee a clear role for sotagliflozin, particularly because of additional facets of the drug’s performance in trials that they perceive give it an edge over dapagliflozin and empagliflozin. This includes evidence that sotagliflozin treatment uniquely (within the SGLT2 inhibitor class) cuts the rate of strokes and myocardial infarctions, as well as evidence of its apparent ability to lower hemoglobin A1c levels in patients with type 2 diabetes and with an estimated glomerular filtration rate below 30 mL/min per 1.73 m², a property likely linked to inhibition of SGLT1 in the gut that dampens intestinal glucose absorption.
 

Sotagliflozin uptake ‘will be a challenge’

“It will be a challenge” for sotagliflozin uptake, given the head start that both dapagliflozin and empagliflozin have had as well-documented agents for patients with heart failure, commented Javed Butler, MD, a heart failure clinician and trialist who is president of the Baylor Scott & White Research Institute in Dallas.

Given the position dapagliflozin and empagliflozin currently have in U.S. heart failure management – with the SGLT2 inhibitor class called out in guidelines as foundational for treating patients with heart failure with reduced ejection fraction and likely soon for heart failure with preserved ejection fraction as well – “I can’t imagine [sotagliflozin] will be considered a preferred option,” Dr. Butler said in an interview.

Another expert was even more dismissive of sotagliflozin’s role.

“There is no persuasive evidence that sotagliflozin has any advantages, compared with the SGLT2 inhibitors, for the treatment of heart failure,” said Milton Packer, MD, a heart failure specialist and trialist at Baylor University Medical Center, Dallas. “I do not see why U.S. physicians might pivot from established SGLT2 inhibitors to sotagliflozin,” unless it was priced “at a very meaningful discount to available SGLT2 inhibitors.”

At the time it announced the FDA’s approval, Lexicon did not provide details on how it would price sotagliflozin. Existing retail prices for dapagliflozin and empagliflozin run about $550-$600/month, a price point that has contributed to slow U.S. uptake of the drug class. But experts anticipate a dramatic shake-up of the U.S. market for SGLT2 inhibitors with expected introduction of a generic SGLT2 inhibitor formulation by 2025, a development that could further dampen sotagliflozin’s prospects.

Other experts are more optimistic about the new agent’s uptake, perhaps none more than Deepak L. Bhatt, MD, MPH, who led both pivotal trials that provide the bulk of sotagliflozin’s evidence package.

copyright CYIM

In addition to SOLOIST-WHF, Dr. Bhatt also headed the SCORED trial, with 10,584 patients with type 2 diabetes, CKD, and risks for cardiovascular disease randomized to sotagliflozin or placebo and followed for a median of 16 months. The primary result showed that sotagliflozin treatment cut the combined rate of deaths from cardiovascular causes, hospitalizations for heart failure, and urgent visits for heart failure by a significant 26% relative to control patients.
 

A clear MACE benefit

“The data from SOLOIST-WHF and SCORED look at least as good as the data for the SGLT2 inhibitors for heart failure, and what appears to be different are the rates for MI and stroke in SCORED,” said Dr. Bhatt, director of Mount Sinai Heart, New York.

“I believe the rate of major adverse cardiovascular events [MACE] were reduced [in SCORED], and this is different from the SGLT2 inhibitors,” he said in an interview.

In 2022, Dr. Bhatt reported results from a prespecified secondary analysis of SCORED that showed that treatment with sotagliflozin cut the rate of MACE by a significant 21%-26%, compared with placebo. This finding was, in part, driven by the first data to show a substantial benefit from an SGLT inhibitor on stroke rates.

And while SCORED did not report a significant benefit for slowing progression of CKD, subsequent post hoc analyses have suggested this advantage also in as-yet-unpublished findings, Dr. Bhatt added.

But he said he doubted nephrologists will see it as a first-line agent for slowing CKD progression – an indication already held by dapagliflozin, pending for empagliflozin, and also in place for a third SGLT2 inhibitor, canagliflozin (Invokana) – because sotagliflozin lacks clear significant and prespecified evidence for this effect.

Dr. Bhatt also acknowledged the limitation of sotagliflozin compared with the SGLT2 inhibitors as an agent for glucose control, again because of no evidence for this effect from a prospective analysis and no pending indication for type 2 diabetes treatment. But the SCORED data showed a clear A1c benefit, even in patients with severely reduced renal function.
 

Mostly for cardiologists? ‘Compelling’ reductions in MIs and strokes

That may mean sotagliflozin “won’t get much use by endocrinologists nor by primary care physicians,” commented Carol L. Wysham, MD, an endocrinologist with MultiCare in Spokane, Wash.

Sotagliflozin “will be a cardiology drug,” and will “have a hard time” competing with the SGLT2 inhibitors, she predicted.

Dr. Bhatt agreed that sotagliflozin “will be perceived as a drug for cardiologists to prescribe. I don’t see endocrinologists, nephrologists, and primary care physicians reaching for this drug if it has a heart failure label.” But, he added, “my hope is that the company files for additional indications. It deserves an indication for glycemic control.”

The evidence for a heart failure benefit from sotagliflozin is “valid and compelling,” and “having this option is great,” commented Mikhail N. Kosiborod, MD, a cardiologist, vice president of research at Saint Luke’s Health System, and codirector of the Haverty Cardiometabolic Center of Excellence at Saint Luke’s Mid America Heart Institute in Kansas City, Mo. But, he added, “it will be a reasonably tall task for sotagliflozin to come from behind and be disruptive in a space where there are already two well-established SGLT2 inhibitors” approved for preventing heart failure hospitalizations, “with a lot of data to back them up,”

The feature that sets sotagliflozin apart from the approved SGLT2 inhibitors is the “really compelling decrease” it produced in rates of MIs and strokes “that we simply do not see with SGLT2 inhibitors,” Dr. Kosiborod said in an interview.

He also cited results from SCORED that suggest “a meaningful reduction in A1c” when indirectly compared with SGLT2 inhibitors, especially in patients with more severe CKD. The lack of a dedicated A1c-lowering trial or an approved type 2 diabetes indication “will not be a problem for cardiologists,” he predicted, but also agreed that it is less likely to be used by primary care physicians in low-risk patients.

“I can see myself prescribing sotagliflozin,” said Dr. Kosiborod, a SCORED coinvestigator, especially for patients with coexisting type 2 diabetes, heart failure, CKD, and atherosclerotic cardiovascular disease. These patients may get “more bang for the buck” because of a reduced risk for MI and stroke, making sotagliflozin “a solid consideration in these patients if the economic factors align.”

Like others, Dr. Kosiborod cited the big impact pricing will have, especially if, as expected, a generic SGLT2 inhibitor soon comes onto the U.S. market. “Access and affordability are very important.”

SOLOIST-WHF and SCORED were sponsored initially by Sanofi and later by Lexicon after Sanofi pulled out of sotagliflozin development. Dr. Butler has been a consultant for Lexicon as well as for AstraZeneca (which markets Farxiga), Boehringer Ingelheim and Lilly (which jointly market Jardiance), and Janssen (which markets Invokana), as well as for numerous other companies. Dr. Packer has been a consultant for AstraZeneca, Boehringer Ingelheim, Lilly, and numerous other companies. Dr. Bhatt was lead investigator for SOLOIST-WHF and SCORED and has been an adviser for Boehringer Ingelheim and Janssen and numerous other companies. Dr. Wysham has been an adviser, speaker, and consultant for AstraZeneca, Boehringer Ingelheim, Lilly, Janssen, Novo Nordisk, and Sanofi, an adviser for Abbott, and a speaker for Insulet. Dr. Kosiborod was a member of the SCORED Steering Committee and has been a consultant for Lexicon, AstraZeneca, Boehringer Ingelheim, Janssen, Lilly, Novo Nordisk, and numerous other companies.

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

Sotagliflozin, a novel agent that inhibits sodium-glucose cotransporter 1 as well as SGLT2, has received marketing approval from the Food and Drug Administration for reducing the risk for cardiovascular death, hospitalization for heart failure, and urgent heart failure visits in patients with heart failure, and also for preventing these same events in patients with type 2 diabetes, chronic kidney disease (CKD), and other cardiovascular disease risk factors.

This puts sotagliflozin in direct competition with two SGLT2 inhibitors, dapagliflozin (Farxiga) and empagliflozin (Jardiance), that already have indications for preventing heart failure hospitalizations in patients with heart failure as well as approvals for type 2 diabetes and preservation of renal function.

Officials at Lexicon Pharmaceuticals, the company that developed and will market sotagliflozin under the trade name Inpefa, said in a press release that they expect U.S. sales of the agent to begin before the end of June 2023. The release also highlighted that the approval broadly covered use in patients with heart failure across the full range of both reduced and preserved left ventricular ejection fractions.

Lexicon officials also said that the company will focus on marketing sotagliflozin for preventing near-term rehospitalizations of patients discharged after an episode of acute heart failure decompensation.

They base this niche target for sotagliflozin on results from the SOLOIST-WHF trial, which randomized 1,222 patients with type 2 diabetes recently hospitalized for worsening heart failure and showed a significant 33% reduction in the rate of deaths from cardiovascular causes and hospitalizations and urgent visits for heart failure, compared with control patients during a median 9 months of follow-up. Nearly half of the enrolled patients received their first dose while still hospitalized, while the other half received their first dose a median of 2 days after hospital discharge. The drug appeared safe.
 

Cutting heart failure rehospitalizations in half

An exploratory post hoc analysis of SOLOIST-WHF showed that treatment with sotagliflozin cut the rate of rehospitalizations roughly in half after both 30 and 90 days compared with control patients, according to an abstract presented at the 2022 annual scientific sessions of the AHA that has not yet been published in a peer-reviewed journal.

The only SGLT2 inhibitor tested so far when initiated in patients during hospitalization for heart failure is empagliflozin, in the EMPULSE trial, which randomized 530 patients. EMPULSE also showed that starting an SGLT2 inhibitor in this setting was safe and resulted in significant clinical benefit, the study’s primary endpoint, defined as a composite of death from any cause, number of heart failure events, and time to first heart failure event, or a 5-point or greater difference in change from baseline in the Kansas City Cardiomyopathy Questionnaire Total Symptom Score at 90 days.

In the DELIVER trial, which tested dapagliflozin in patients with heart failure with preserved ejection fraction, roughly 10% of patients started study treatment during or within 30 days of heart failure hospitalization, and in this subgroup, dapagliflozin appeared as effective as it was in the other 90% of patients who did not start the drug during an acute or subacute phase.

Despite the SOLOIST-WHF evidence for sotagliflozin’s safety and efficacy in this economically important clinical setting, some experts say the drug faces an uphill path as it contends for market share against two solidly established, albeit dramatically underused, SGLT2 inhibitors. (Recent data document that 20% or fewer of U.S. patients eligible for treatment with an SGLT2 inhibitor receive it, such as a review of 49,000 patients hospitalized during 2021-2022 with heart failure with reduced ejection fraction.)

Others foresee a clear role for sotagliflozin, particularly because of additional facets of the drug’s performance in trials that they perceive give it an edge over dapagliflozin and empagliflozin. This includes evidence that sotagliflozin treatment uniquely (within the SGLT2 inhibitor class) cuts the rate of strokes and myocardial infarctions, as well as evidence of its apparent ability to lower hemoglobin A1c levels in patients with type 2 diabetes and with an estimated glomerular filtration rate below 30 mL/min per 1.73 m², a property likely linked to inhibition of SGLT1 in the gut that dampens intestinal glucose absorption.
 

Sotagliflozin uptake ‘will be a challenge’

“It will be a challenge” for sotagliflozin uptake, given the head start that both dapagliflozin and empagliflozin have had as well-documented agents for patients with heart failure, commented Javed Butler, MD, a heart failure clinician and trialist who is president of the Baylor Scott & White Research Institute in Dallas.

Given the position dapagliflozin and empagliflozin currently have in U.S. heart failure management – with the SGLT2 inhibitor class called out in guidelines as foundational for treating patients with heart failure with reduced ejection fraction and likely soon for heart failure with preserved ejection fraction as well – “I can’t imagine [sotagliflozin] will be considered a preferred option,” Dr. Butler said in an interview.

Another expert was even more dismissive of sotagliflozin’s role.

“There is no persuasive evidence that sotagliflozin has any advantages, compared with the SGLT2 inhibitors, for the treatment of heart failure,” said Milton Packer, MD, a heart failure specialist and trialist at Baylor University Medical Center, Dallas. “I do not see why U.S. physicians might pivot from established SGLT2 inhibitors to sotagliflozin,” unless it was priced “at a very meaningful discount to available SGLT2 inhibitors.”

At the time it announced the FDA’s approval, Lexicon did not provide details on how it would price sotagliflozin. Existing retail prices for dapagliflozin and empagliflozin run about $550-$600/month, a price point that has contributed to slow U.S. uptake of the drug class. But experts anticipate a dramatic shake-up of the U.S. market for SGLT2 inhibitors with expected introduction of a generic SGLT2 inhibitor formulation by 2025, a development that could further dampen sotagliflozin’s prospects.

Other experts are more optimistic about the new agent’s uptake, perhaps none more than Deepak L. Bhatt, MD, MPH, who led both pivotal trials that provide the bulk of sotagliflozin’s evidence package.

copyright CYIM

In addition to SOLOIST-WHF, Dr. Bhatt also headed the SCORED trial, with 10,584 patients with type 2 diabetes, CKD, and risks for cardiovascular disease randomized to sotagliflozin or placebo and followed for a median of 16 months. The primary result showed that sotagliflozin treatment cut the combined rate of deaths from cardiovascular causes, hospitalizations for heart failure, and urgent visits for heart failure by a significant 26% relative to control patients.
 

A clear MACE benefit

“The data from SOLOIST-WHF and SCORED look at least as good as the data for the SGLT2 inhibitors for heart failure, and what appears to be different are the rates for MI and stroke in SCORED,” said Dr. Bhatt, director of Mount Sinai Heart, New York.

“I believe the rate of major adverse cardiovascular events [MACE] were reduced [in SCORED], and this is different from the SGLT2 inhibitors,” he said in an interview.

In 2022, Dr. Bhatt reported results from a prespecified secondary analysis of SCORED that showed that treatment with sotagliflozin cut the rate of MACE by a significant 21%-26%, compared with placebo. This finding was, in part, driven by the first data to show a substantial benefit from an SGLT inhibitor on stroke rates.

And while SCORED did not report a significant benefit for slowing progression of CKD, subsequent post hoc analyses have suggested this advantage also in as-yet-unpublished findings, Dr. Bhatt added.

But he said he doubted nephrologists will see it as a first-line agent for slowing CKD progression – an indication already held by dapagliflozin, pending for empagliflozin, and also in place for a third SGLT2 inhibitor, canagliflozin (Invokana) – because sotagliflozin lacks clear significant and prespecified evidence for this effect.

Dr. Bhatt also acknowledged the limitation of sotagliflozin compared with the SGLT2 inhibitors as an agent for glucose control, again because of no evidence for this effect from a prospective analysis and no pending indication for type 2 diabetes treatment. But the SCORED data showed a clear A1c benefit, even in patients with severely reduced renal function.
 

Mostly for cardiologists? ‘Compelling’ reductions in MIs and strokes

That may mean sotagliflozin “won’t get much use by endocrinologists nor by primary care physicians,” commented Carol L. Wysham, MD, an endocrinologist with MultiCare in Spokane, Wash.

Sotagliflozin “will be a cardiology drug,” and will “have a hard time” competing with the SGLT2 inhibitors, she predicted.

Dr. Bhatt agreed that sotagliflozin “will be perceived as a drug for cardiologists to prescribe. I don’t see endocrinologists, nephrologists, and primary care physicians reaching for this drug if it has a heart failure label.” But, he added, “my hope is that the company files for additional indications. It deserves an indication for glycemic control.”

The evidence for a heart failure benefit from sotagliflozin is “valid and compelling,” and “having this option is great,” commented Mikhail N. Kosiborod, MD, a cardiologist, vice president of research at Saint Luke’s Health System, and codirector of the Haverty Cardiometabolic Center of Excellence at Saint Luke’s Mid America Heart Institute in Kansas City, Mo. But, he added, “it will be a reasonably tall task for sotagliflozin to come from behind and be disruptive in a space where there are already two well-established SGLT2 inhibitors” approved for preventing heart failure hospitalizations, “with a lot of data to back them up,”

The feature that sets sotagliflozin apart from the approved SGLT2 inhibitors is the “really compelling decrease” it produced in rates of MIs and strokes “that we simply do not see with SGLT2 inhibitors,” Dr. Kosiborod said in an interview.

He also cited results from SCORED that suggest “a meaningful reduction in A1c” when indirectly compared with SGLT2 inhibitors, especially in patients with more severe CKD. The lack of a dedicated A1c-lowering trial or an approved type 2 diabetes indication “will not be a problem for cardiologists,” he predicted, but also agreed that it is less likely to be used by primary care physicians in low-risk patients.

“I can see myself prescribing sotagliflozin,” said Dr. Kosiborod, a SCORED coinvestigator, especially for patients with coexisting type 2 diabetes, heart failure, CKD, and atherosclerotic cardiovascular disease. These patients may get “more bang for the buck” because of a reduced risk for MI and stroke, making sotagliflozin “a solid consideration in these patients if the economic factors align.”

Like others, Dr. Kosiborod cited the big impact pricing will have, especially if, as expected, a generic SGLT2 inhibitor soon comes onto the U.S. market. “Access and affordability are very important.”

SOLOIST-WHF and SCORED were sponsored initially by Sanofi and later by Lexicon after Sanofi pulled out of sotagliflozin development. Dr. Butler has been a consultant for Lexicon as well as for AstraZeneca (which markets Farxiga), Boehringer Ingelheim and Lilly (which jointly market Jardiance), and Janssen (which markets Invokana), as well as for numerous other companies. Dr. Packer has been a consultant for AstraZeneca, Boehringer Ingelheim, Lilly, and numerous other companies. Dr. Bhatt was lead investigator for SOLOIST-WHF and SCORED and has been an adviser for Boehringer Ingelheim and Janssen and numerous other companies. Dr. Wysham has been an adviser, speaker, and consultant for AstraZeneca, Boehringer Ingelheim, Lilly, Janssen, Novo Nordisk, and Sanofi, an adviser for Abbott, and a speaker for Insulet. Dr. Kosiborod was a member of the SCORED Steering Committee and has been a consultant for Lexicon, AstraZeneca, Boehringer Ingelheim, Janssen, Lilly, Novo Nordisk, and numerous other companies.

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

Sotagliflozin, a novel agent that inhibits sodium-glucose cotransporter 1 as well as SGLT2, has received marketing approval from the Food and Drug Administration for reducing the risk for cardiovascular death, hospitalization for heart failure, and urgent heart failure visits in patients with heart failure, and also for preventing these same events in patients with type 2 diabetes, chronic kidney disease (CKD), and other cardiovascular disease risk factors.

This puts sotagliflozin in direct competition with two SGLT2 inhibitors, dapagliflozin (Farxiga) and empagliflozin (Jardiance), that already have indications for preventing heart failure hospitalizations in patients with heart failure as well as approvals for type 2 diabetes and preservation of renal function.

Officials at Lexicon Pharmaceuticals, the company that developed and will market sotagliflozin under the trade name Inpefa, said in a press release that they expect U.S. sales of the agent to begin before the end of June 2023. The release also highlighted that the approval broadly covered use in patients with heart failure across the full range of both reduced and preserved left ventricular ejection fractions.

Lexicon officials also said that the company will focus on marketing sotagliflozin for preventing near-term rehospitalizations of patients discharged after an episode of acute heart failure decompensation.

They base this niche target for sotagliflozin on results from the SOLOIST-WHF trial, which randomized 1,222 patients with type 2 diabetes recently hospitalized for worsening heart failure and showed a significant 33% reduction in the rate of deaths from cardiovascular causes and hospitalizations and urgent visits for heart failure, compared with control patients during a median 9 months of follow-up. Nearly half of the enrolled patients received their first dose while still hospitalized, while the other half received their first dose a median of 2 days after hospital discharge. The drug appeared safe.
 

Cutting heart failure rehospitalizations in half

An exploratory post hoc analysis of SOLOIST-WHF showed that treatment with sotagliflozin cut the rate of rehospitalizations roughly in half after both 30 and 90 days compared with control patients, according to an abstract presented at the 2022 annual scientific sessions of the AHA that has not yet been published in a peer-reviewed journal.

The only SGLT2 inhibitor tested so far when initiated in patients during hospitalization for heart failure is empagliflozin, in the EMPULSE trial, which randomized 530 patients. EMPULSE also showed that starting an SGLT2 inhibitor in this setting was safe and resulted in significant clinical benefit, the study’s primary endpoint, defined as a composite of death from any cause, number of heart failure events, and time to first heart failure event, or a 5-point or greater difference in change from baseline in the Kansas City Cardiomyopathy Questionnaire Total Symptom Score at 90 days.

In the DELIVER trial, which tested dapagliflozin in patients with heart failure with preserved ejection fraction, roughly 10% of patients started study treatment during or within 30 days of heart failure hospitalization, and in this subgroup, dapagliflozin appeared as effective as it was in the other 90% of patients who did not start the drug during an acute or subacute phase.

Despite the SOLOIST-WHF evidence for sotagliflozin’s safety and efficacy in this economically important clinical setting, some experts say the drug faces an uphill path as it contends for market share against two solidly established, albeit dramatically underused, SGLT2 inhibitors. (Recent data document that 20% or fewer of U.S. patients eligible for treatment with an SGLT2 inhibitor receive it, such as a review of 49,000 patients hospitalized during 2021-2022 with heart failure with reduced ejection fraction.)

Others foresee a clear role for sotagliflozin, particularly because of additional facets of the drug’s performance in trials that they perceive give it an edge over dapagliflozin and empagliflozin. This includes evidence that sotagliflozin treatment uniquely (within the SGLT2 inhibitor class) cuts the rate of strokes and myocardial infarctions, as well as evidence of its apparent ability to lower hemoglobin A1c levels in patients with type 2 diabetes and with an estimated glomerular filtration rate below 30 mL/min per 1.73 m², a property likely linked to inhibition of SGLT1 in the gut that dampens intestinal glucose absorption.
 

Sotagliflozin uptake ‘will be a challenge’

“It will be a challenge” for sotagliflozin uptake, given the head start that both dapagliflozin and empagliflozin have had as well-documented agents for patients with heart failure, commented Javed Butler, MD, a heart failure clinician and trialist who is president of the Baylor Scott & White Research Institute in Dallas.

Given the position dapagliflozin and empagliflozin currently have in U.S. heart failure management – with the SGLT2 inhibitor class called out in guidelines as foundational for treating patients with heart failure with reduced ejection fraction and likely soon for heart failure with preserved ejection fraction as well – “I can’t imagine [sotagliflozin] will be considered a preferred option,” Dr. Butler said in an interview.

Another expert was even more dismissive of sotagliflozin’s role.

“There is no persuasive evidence that sotagliflozin has any advantages, compared with the SGLT2 inhibitors, for the treatment of heart failure,” said Milton Packer, MD, a heart failure specialist and trialist at Baylor University Medical Center, Dallas. “I do not see why U.S. physicians might pivot from established SGLT2 inhibitors to sotagliflozin,” unless it was priced “at a very meaningful discount to available SGLT2 inhibitors.”

At the time it announced the FDA’s approval, Lexicon did not provide details on how it would price sotagliflozin. Existing retail prices for dapagliflozin and empagliflozin run about $550-$600/month, a price point that has contributed to slow U.S. uptake of the drug class. But experts anticipate a dramatic shake-up of the U.S. market for SGLT2 inhibitors with expected introduction of a generic SGLT2 inhibitor formulation by 2025, a development that could further dampen sotagliflozin’s prospects.

Other experts are more optimistic about the new agent’s uptake, perhaps none more than Deepak L. Bhatt, MD, MPH, who led both pivotal trials that provide the bulk of sotagliflozin’s evidence package.

copyright CYIM

In addition to SOLOIST-WHF, Dr. Bhatt also headed the SCORED trial, with 10,584 patients with type 2 diabetes, CKD, and risks for cardiovascular disease randomized to sotagliflozin or placebo and followed for a median of 16 months. The primary result showed that sotagliflozin treatment cut the combined rate of deaths from cardiovascular causes, hospitalizations for heart failure, and urgent visits for heart failure by a significant 26% relative to control patients.
 

A clear MACE benefit

“The data from SOLOIST-WHF and SCORED look at least as good as the data for the SGLT2 inhibitors for heart failure, and what appears to be different are the rates for MI and stroke in SCORED,” said Dr. Bhatt, director of Mount Sinai Heart, New York.

“I believe the rate of major adverse cardiovascular events [MACE] were reduced [in SCORED], and this is different from the SGLT2 inhibitors,” he said in an interview.

In 2022, Dr. Bhatt reported results from a prespecified secondary analysis of SCORED that showed that treatment with sotagliflozin cut the rate of MACE by a significant 21%-26%, compared with placebo. This finding was, in part, driven by the first data to show a substantial benefit from an SGLT inhibitor on stroke rates.

And while SCORED did not report a significant benefit for slowing progression of CKD, subsequent post hoc analyses have suggested this advantage also in as-yet-unpublished findings, Dr. Bhatt added.

But he said he doubted nephrologists will see it as a first-line agent for slowing CKD progression – an indication already held by dapagliflozin, pending for empagliflozin, and also in place for a third SGLT2 inhibitor, canagliflozin (Invokana) – because sotagliflozin lacks clear significant and prespecified evidence for this effect.

Dr. Bhatt also acknowledged the limitation of sotagliflozin compared with the SGLT2 inhibitors as an agent for glucose control, again because of no evidence for this effect from a prospective analysis and no pending indication for type 2 diabetes treatment. But the SCORED data showed a clear A1c benefit, even in patients with severely reduced renal function.
 

Mostly for cardiologists? ‘Compelling’ reductions in MIs and strokes

That may mean sotagliflozin “won’t get much use by endocrinologists nor by primary care physicians,” commented Carol L. Wysham, MD, an endocrinologist with MultiCare in Spokane, Wash.

Sotagliflozin “will be a cardiology drug,” and will “have a hard time” competing with the SGLT2 inhibitors, she predicted.

Dr. Bhatt agreed that sotagliflozin “will be perceived as a drug for cardiologists to prescribe. I don’t see endocrinologists, nephrologists, and primary care physicians reaching for this drug if it has a heart failure label.” But, he added, “my hope is that the company files for additional indications. It deserves an indication for glycemic control.”

The evidence for a heart failure benefit from sotagliflozin is “valid and compelling,” and “having this option is great,” commented Mikhail N. Kosiborod, MD, a cardiologist, vice president of research at Saint Luke’s Health System, and codirector of the Haverty Cardiometabolic Center of Excellence at Saint Luke’s Mid America Heart Institute in Kansas City, Mo. But, he added, “it will be a reasonably tall task for sotagliflozin to come from behind and be disruptive in a space where there are already two well-established SGLT2 inhibitors” approved for preventing heart failure hospitalizations, “with a lot of data to back them up,”

The feature that sets sotagliflozin apart from the approved SGLT2 inhibitors is the “really compelling decrease” it produced in rates of MIs and strokes “that we simply do not see with SGLT2 inhibitors,” Dr. Kosiborod said in an interview.

He also cited results from SCORED that suggest “a meaningful reduction in A1c” when indirectly compared with SGLT2 inhibitors, especially in patients with more severe CKD. The lack of a dedicated A1c-lowering trial or an approved type 2 diabetes indication “will not be a problem for cardiologists,” he predicted, but also agreed that it is less likely to be used by primary care physicians in low-risk patients.

“I can see myself prescribing sotagliflozin,” said Dr. Kosiborod, a SCORED coinvestigator, especially for patients with coexisting type 2 diabetes, heart failure, CKD, and atherosclerotic cardiovascular disease. These patients may get “more bang for the buck” because of a reduced risk for MI and stroke, making sotagliflozin “a solid consideration in these patients if the economic factors align.”

Like others, Dr. Kosiborod cited the big impact pricing will have, especially if, as expected, a generic SGLT2 inhibitor soon comes onto the U.S. market. “Access and affordability are very important.”

SOLOIST-WHF and SCORED were sponsored initially by Sanofi and later by Lexicon after Sanofi pulled out of sotagliflozin development. Dr. Butler has been a consultant for Lexicon as well as for AstraZeneca (which markets Farxiga), Boehringer Ingelheim and Lilly (which jointly market Jardiance), and Janssen (which markets Invokana), as well as for numerous other companies. Dr. Packer has been a consultant for AstraZeneca, Boehringer Ingelheim, Lilly, and numerous other companies. Dr. Bhatt was lead investigator for SOLOIST-WHF and SCORED and has been an adviser for Boehringer Ingelheim and Janssen and numerous other companies. Dr. Wysham has been an adviser, speaker, and consultant for AstraZeneca, Boehringer Ingelheim, Lilly, Janssen, Novo Nordisk, and Sanofi, an adviser for Abbott, and a speaker for Insulet. Dr. Kosiborod was a member of the SCORED Steering Committee and has been a consultant for Lexicon, AstraZeneca, Boehringer Ingelheim, Janssen, Lilly, Novo Nordisk, and numerous other companies.

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

People who followed a vegan or vegetarian diet had lower blood levels of low-density lipoprotein cholesterol (LDL-C), total cholesterol, and apolipoprotein B (apoB) than people who followed an omnivore diet, in a new meta-analysis of 30 trials.

The findings suggest that “plant-based diets have the potential to lessen the atherosclerotic burden from atherogenic lipoproteins and thereby reduce the risk of cardiovascular disease,” write Caroline Amelie Koch, a medical student at the University of Copenhagen, and colleagues. Their findings were published online in the European Heart Journal (2023 May 24. doi: 10.1093/eurheartj/ehad211).

“Vegetarian and vegan diets were associated with a 14% reduction in all artery-clogging lipoproteins as indicated by apoB,” senior author Ruth Frikke-Schmidt, DMSc, PhD, Rigshospitalet, Copenhagen, and professor, University of Copenhagen, said in a press release from her university.

“This corresponds to a third of the effect of taking cholesterol-lowering medications such as statins,” she added, “and would result in a 7% reduction in the risk of cardiovascular disease in someone who maintained a plant-based diet for 5 years.”

gerenme/ThinkStock

More support for vegan, vegetarian diets

These new findings “add to the body of evidence supporting favorable effects of healthy vegan and vegetarian dietary patterns on circulating levels of LDL-C and atherogenic lipoproteins, which would be expected to reduce ASCVD risk,” Kevin C. Maki, PhD, and Carol Kirkpatrick, PhD, MPH, write in an accompanying editorial.

“While it is not necessary to entirely omit foods such as meat, poultry, and fish/seafood to follow a recommended dietary pattern, reducing consumption of such foods is a reasonable option for those who prefer to do so,” note Dr. Maki, of Indiana University School of Public Health, Bloomington, and Kirkpatrick, of Idaho State University, Pocatello.
 

Plant-based diet needs to be ‘well-planned’

Several experts who were not involved in this meta-analysis shed light on the study and its implications in comments to the U.K. Science Media Center.

“Although a vegetarian and vegan diet can be very healthy and beneficial with respect to cardiovascular risk, it is important that it is well planned so that nutrients it can be low in are included, including iron, iodine, vitamin B12, and vitamin D,” said Duane Mellor, PhD, a registered dietitian and senior lecturer, Aston Medical School, Aston University, Birmingham, England.

Some people “may find it easier to follow a Mediterranean-style diet that features plenty of fruit, vegetables, pulses, wholegrains, fish, eggs and low-fat dairy, with only small amounts of meat,” Tracy Parker, senior dietitian at the British Heart Foundation, London, suggested.

“There is considerable evidence that this type of diet can help lower your risk of developing heart and circulatory diseases by improving cholesterol and blood pressure levels, reducing inflammation, and controlling blood glucose levels,” she added.

And Aedin Cassidy, PhD, chair in nutrition & preventative medicine, Queen’s University Belfast (Ireland), noted that “not all plant-based diets are equal. Healthy plant-based diets, characterized by fruits, vegetables, and whole grains improve health, but other plant diets (for example, those including refined carbohydrates, processed foods high in fat/salt, etc.) do not.”  

This new study shows that plant-based diets have the potential to improve health by improving blood lipids, “but this is one of many potential mechanisms, including impact on blood pressure, weight maintenance, and blood sugars,” she added.

“This work represents a well-conducted analysis of 30 clinical trials involving over two thousand participants and highlights the value of a vegetarian diet in reducing the risk of heart attack or stroke through reduction in blood cholesterol levels,” said Robert Storey, BM, DM, professor of cardiology, University of Sheffield, U.K.

However, it also demonstrates that the impact of diet on an individual’s cholesterol level is relatively limited, he added.

“This is because people inherit the tendency for their livers to produce too much cholesterol, meaning that high cholesterol is more strongly influenced by our genes than by our diet,” he explained.

This is “why statins are needed to block cholesterol production in people who are at higher risk of or have already suffered from a heart attack, stroke, or other illness related to cholesterol build-up in blood vessels.”
 

Beneficial effect on ApoB, LDL-C, and total cholesterol

ApoB is the main apolipoprotein in LDL-C (“bad” cholesterol), the researchers note. Previous studies have shown that LDL-C and apoB-containing particles are associated with increased risk of ASCVD.

They aimed to estimate the effect of vegetarian or vegan diets on blood levels of total cholesterol, LDL-C, triglycerides, and apoB in people randomized to a vegetarian or vegan diet versus an omnivorous diet (that is, including meat and dairy).

They identified 30 studies published between 1982 and 2022 and conducted in the United States (18 studies), Sweden (2), Finland (2), South Korea (2), Australia (1), Brazil (1), Czech Republic (1), Italy (1), Iran (1), and New Zealand (1).

The diet interventions lasted from 10 days to 5 years with a mean of 29 weeks (15 studies ≤ 3 months; 12 studies 3-12 months; and three studies > 1 year). Nine studies used a crossover design, and the rest used a parallel design whereby participants followed only one diet.

The studies had 11 to 291 participants (mean, 79 participants) with a mean BMI of 21.5-35.1 kg/m² and a mean age of 20-67 years. Thirteen studies included participants treated with lipid-lowering therapy at baseline.

The dietary intervention was vegetarian in 15 trials (three lacto-vegetarian and 12 lacto-ovo-vegetarian) and vegan in the other 15 trials.

On average, compared with people eating an omnivore diet, people eating a plant-based diet had a 7% reduction in total cholesterol from baseline (–0.34 mmol/L), a 10% reduction in LDL-C from baseline (–0.30 mmol/L), and a 14% reduction in apoB from baseline (–12.9 mg/dL) (all P < .01).

The effects were similar across age, continent, study duration, health status, intervention diet, intervention program, and study design subgroups.

There was no significant difference in triglyceride levels in patients in the omnivore versus plant-based diet groups.
 

Such diets could considerably reduce greenhouse gases

Senior author Dr. Frikke-Schmidt noted: “Recent systematic reviews have shown that if the populations of high-income countries shift to plant-based diets, this can reduce net emissions of greenhouse gases by between 35% to 49%.”

“Plant-based diets are key instruments for changing food production to more environmentally sustainable forms, while at the same time reducing the burden of cardiovascular disease” in an aging population, she said.

“We should be eating a varied, plant-rich diet, not too much, and quenching our thirst with water,” she concluded.

The study was funded by the Lundbeck Foundation, the Danish Heart Foundation, and the Leducq Foundation. The authors, editorialists, Ms. Parker, Dr. Cassidy, and Dr. Storey have reported no relevant financial relationships. Dr. Mellor has disclosed that he is a vegetarian.

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

People who followed a vegan or vegetarian diet had lower blood levels of low-density lipoprotein cholesterol (LDL-C), total cholesterol, and apolipoprotein B (apoB) than people who followed an omnivore diet, in a new meta-analysis of 30 trials.

The findings suggest that “plant-based diets have the potential to lessen the atherosclerotic burden from atherogenic lipoproteins and thereby reduce the risk of cardiovascular disease,” write Caroline Amelie Koch, a medical student at the University of Copenhagen, and colleagues. Their findings were published online in the European Heart Journal (2023 May 24. doi: 10.1093/eurheartj/ehad211).

“Vegetarian and vegan diets were associated with a 14% reduction in all artery-clogging lipoproteins as indicated by apoB,” senior author Ruth Frikke-Schmidt, DMSc, PhD, Rigshospitalet, Copenhagen, and professor, University of Copenhagen, said in a press release from her university.

“This corresponds to a third of the effect of taking cholesterol-lowering medications such as statins,” she added, “and would result in a 7% reduction in the risk of cardiovascular disease in someone who maintained a plant-based diet for 5 years.”

gerenme/ThinkStock

More support for vegan, vegetarian diets

These new findings “add to the body of evidence supporting favorable effects of healthy vegan and vegetarian dietary patterns on circulating levels of LDL-C and atherogenic lipoproteins, which would be expected to reduce ASCVD risk,” Kevin C. Maki, PhD, and Carol Kirkpatrick, PhD, MPH, write in an accompanying editorial.

“While it is not necessary to entirely omit foods such as meat, poultry, and fish/seafood to follow a recommended dietary pattern, reducing consumption of such foods is a reasonable option for those who prefer to do so,” note Dr. Maki, of Indiana University School of Public Health, Bloomington, and Kirkpatrick, of Idaho State University, Pocatello.
 

Plant-based diet needs to be ‘well-planned’

Several experts who were not involved in this meta-analysis shed light on the study and its implications in comments to the U.K. Science Media Center.

“Although a vegetarian and vegan diet can be very healthy and beneficial with respect to cardiovascular risk, it is important that it is well planned so that nutrients it can be low in are included, including iron, iodine, vitamin B12, and vitamin D,” said Duane Mellor, PhD, a registered dietitian and senior lecturer, Aston Medical School, Aston University, Birmingham, England.

Some people “may find it easier to follow a Mediterranean-style diet that features plenty of fruit, vegetables, pulses, wholegrains, fish, eggs and low-fat dairy, with only small amounts of meat,” Tracy Parker, senior dietitian at the British Heart Foundation, London, suggested.

“There is considerable evidence that this type of diet can help lower your risk of developing heart and circulatory diseases by improving cholesterol and blood pressure levels, reducing inflammation, and controlling blood glucose levels,” she added.

And Aedin Cassidy, PhD, chair in nutrition & preventative medicine, Queen’s University Belfast (Ireland), noted that “not all plant-based diets are equal. Healthy plant-based diets, characterized by fruits, vegetables, and whole grains improve health, but other plant diets (for example, those including refined carbohydrates, processed foods high in fat/salt, etc.) do not.”  

This new study shows that plant-based diets have the potential to improve health by improving blood lipids, “but this is one of many potential mechanisms, including impact on blood pressure, weight maintenance, and blood sugars,” she added.

“This work represents a well-conducted analysis of 30 clinical trials involving over two thousand participants and highlights the value of a vegetarian diet in reducing the risk of heart attack or stroke through reduction in blood cholesterol levels,” said Robert Storey, BM, DM, professor of cardiology, University of Sheffield, U.K.

However, it also demonstrates that the impact of diet on an individual’s cholesterol level is relatively limited, he added.

“This is because people inherit the tendency for their livers to produce too much cholesterol, meaning that high cholesterol is more strongly influenced by our genes than by our diet,” he explained.

This is “why statins are needed to block cholesterol production in people who are at higher risk of or have already suffered from a heart attack, stroke, or other illness related to cholesterol build-up in blood vessels.”
 

Beneficial effect on ApoB, LDL-C, and total cholesterol

ApoB is the main apolipoprotein in LDL-C (“bad” cholesterol), the researchers note. Previous studies have shown that LDL-C and apoB-containing particles are associated with increased risk of ASCVD.

They aimed to estimate the effect of vegetarian or vegan diets on blood levels of total cholesterol, LDL-C, triglycerides, and apoB in people randomized to a vegetarian or vegan diet versus an omnivorous diet (that is, including meat and dairy).

They identified 30 studies published between 1982 and 2022 and conducted in the United States (18 studies), Sweden (2), Finland (2), South Korea (2), Australia (1), Brazil (1), Czech Republic (1), Italy (1), Iran (1), and New Zealand (1).

The diet interventions lasted from 10 days to 5 years with a mean of 29 weeks (15 studies ≤ 3 months; 12 studies 3-12 months; and three studies > 1 year). Nine studies used a crossover design, and the rest used a parallel design whereby participants followed only one diet.

The studies had 11 to 291 participants (mean, 79 participants) with a mean BMI of 21.5-35.1 kg/m² and a mean age of 20-67 years. Thirteen studies included participants treated with lipid-lowering therapy at baseline.

The dietary intervention was vegetarian in 15 trials (three lacto-vegetarian and 12 lacto-ovo-vegetarian) and vegan in the other 15 trials.

On average, compared with people eating an omnivore diet, people eating a plant-based diet had a 7% reduction in total cholesterol from baseline (–0.34 mmol/L), a 10% reduction in LDL-C from baseline (–0.30 mmol/L), and a 14% reduction in apoB from baseline (–12.9 mg/dL) (all P < .01).

The effects were similar across age, continent, study duration, health status, intervention diet, intervention program, and study design subgroups.

There was no significant difference in triglyceride levels in patients in the omnivore versus plant-based diet groups.
 

Such diets could considerably reduce greenhouse gases

Senior author Dr. Frikke-Schmidt noted: “Recent systematic reviews have shown that if the populations of high-income countries shift to plant-based diets, this can reduce net emissions of greenhouse gases by between 35% to 49%.”

“Plant-based diets are key instruments for changing food production to more environmentally sustainable forms, while at the same time reducing the burden of cardiovascular disease” in an aging population, she said.

“We should be eating a varied, plant-rich diet, not too much, and quenching our thirst with water,” she concluded.

The study was funded by the Lundbeck Foundation, the Danish Heart Foundation, and the Leducq Foundation. The authors, editorialists, Ms. Parker, Dr. Cassidy, and Dr. Storey have reported no relevant financial relationships. Dr. Mellor has disclosed that he is a vegetarian.

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

People who followed a vegan or vegetarian diet had lower blood levels of low-density lipoprotein cholesterol (LDL-C), total cholesterol, and apolipoprotein B (apoB) than people who followed an omnivore diet, in a new meta-analysis of 30 trials.

The findings suggest that “plant-based diets have the potential to lessen the atherosclerotic burden from atherogenic lipoproteins and thereby reduce the risk of cardiovascular disease,” write Caroline Amelie Koch, a medical student at the University of Copenhagen, and colleagues. Their findings were published online in the European Heart Journal (2023 May 24. doi: 10.1093/eurheartj/ehad211).

“Vegetarian and vegan diets were associated with a 14% reduction in all artery-clogging lipoproteins as indicated by apoB,” senior author Ruth Frikke-Schmidt, DMSc, PhD, Rigshospitalet, Copenhagen, and professor, University of Copenhagen, said in a press release from her university.

“This corresponds to a third of the effect of taking cholesterol-lowering medications such as statins,” she added, “and would result in a 7% reduction in the risk of cardiovascular disease in someone who maintained a plant-based diet for 5 years.”

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More support for vegan, vegetarian diets

These new findings “add to the body of evidence supporting favorable effects of healthy vegan and vegetarian dietary patterns on circulating levels of LDL-C and atherogenic lipoproteins, which would be expected to reduce ASCVD risk,” Kevin C. Maki, PhD, and Carol Kirkpatrick, PhD, MPH, write in an accompanying editorial.

“While it is not necessary to entirely omit foods such as meat, poultry, and fish/seafood to follow a recommended dietary pattern, reducing consumption of such foods is a reasonable option for those who prefer to do so,” note Dr. Maki, of Indiana University School of Public Health, Bloomington, and Kirkpatrick, of Idaho State University, Pocatello.
 

Plant-based diet needs to be ‘well-planned’

Several experts who were not involved in this meta-analysis shed light on the study and its implications in comments to the U.K. Science Media Center.

“Although a vegetarian and vegan diet can be very healthy and beneficial with respect to cardiovascular risk, it is important that it is well planned so that nutrients it can be low in are included, including iron, iodine, vitamin B12, and vitamin D,” said Duane Mellor, PhD, a registered dietitian and senior lecturer, Aston Medical School, Aston University, Birmingham, England.

Some people “may find it easier to follow a Mediterranean-style diet that features plenty of fruit, vegetables, pulses, wholegrains, fish, eggs and low-fat dairy, with only small amounts of meat,” Tracy Parker, senior dietitian at the British Heart Foundation, London, suggested.

“There is considerable evidence that this type of diet can help lower your risk of developing heart and circulatory diseases by improving cholesterol and blood pressure levels, reducing inflammation, and controlling blood glucose levels,” she added.

And Aedin Cassidy, PhD, chair in nutrition & preventative medicine, Queen’s University Belfast (Ireland), noted that “not all plant-based diets are equal. Healthy plant-based diets, characterized by fruits, vegetables, and whole grains improve health, but other plant diets (for example, those including refined carbohydrates, processed foods high in fat/salt, etc.) do not.”  

This new study shows that plant-based diets have the potential to improve health by improving blood lipids, “but this is one of many potential mechanisms, including impact on blood pressure, weight maintenance, and blood sugars,” she added.

“This work represents a well-conducted analysis of 30 clinical trials involving over two thousand participants and highlights the value of a vegetarian diet in reducing the risk of heart attack or stroke through reduction in blood cholesterol levels,” said Robert Storey, BM, DM, professor of cardiology, University of Sheffield, U.K.

However, it also demonstrates that the impact of diet on an individual’s cholesterol level is relatively limited, he added.

“This is because people inherit the tendency for their livers to produce too much cholesterol, meaning that high cholesterol is more strongly influenced by our genes than by our diet,” he explained.

This is “why statins are needed to block cholesterol production in people who are at higher risk of or have already suffered from a heart attack, stroke, or other illness related to cholesterol build-up in blood vessels.”
 

Beneficial effect on ApoB, LDL-C, and total cholesterol

ApoB is the main apolipoprotein in LDL-C (“bad” cholesterol), the researchers note. Previous studies have shown that LDL-C and apoB-containing particles are associated with increased risk of ASCVD.

They aimed to estimate the effect of vegetarian or vegan diets on blood levels of total cholesterol, LDL-C, triglycerides, and apoB in people randomized to a vegetarian or vegan diet versus an omnivorous diet (that is, including meat and dairy).

They identified 30 studies published between 1982 and 2022 and conducted in the United States (18 studies), Sweden (2), Finland (2), South Korea (2), Australia (1), Brazil (1), Czech Republic (1), Italy (1), Iran (1), and New Zealand (1).

The diet interventions lasted from 10 days to 5 years with a mean of 29 weeks (15 studies ≤ 3 months; 12 studies 3-12 months; and three studies > 1 year). Nine studies used a crossover design, and the rest used a parallel design whereby participants followed only one diet.

The studies had 11 to 291 participants (mean, 79 participants) with a mean BMI of 21.5-35.1 kg/m² and a mean age of 20-67 years. Thirteen studies included participants treated with lipid-lowering therapy at baseline.

The dietary intervention was vegetarian in 15 trials (three lacto-vegetarian and 12 lacto-ovo-vegetarian) and vegan in the other 15 trials.

On average, compared with people eating an omnivore diet, people eating a plant-based diet had a 7% reduction in total cholesterol from baseline (–0.34 mmol/L), a 10% reduction in LDL-C from baseline (–0.30 mmol/L), and a 14% reduction in apoB from baseline (–12.9 mg/dL) (all P < .01).

The effects were similar across age, continent, study duration, health status, intervention diet, intervention program, and study design subgroups.

There was no significant difference in triglyceride levels in patients in the omnivore versus plant-based diet groups.
 

Such diets could considerably reduce greenhouse gases

Senior author Dr. Frikke-Schmidt noted: “Recent systematic reviews have shown that if the populations of high-income countries shift to plant-based diets, this can reduce net emissions of greenhouse gases by between 35% to 49%.”

“Plant-based diets are key instruments for changing food production to more environmentally sustainable forms, while at the same time reducing the burden of cardiovascular disease” in an aging population, she said.

“We should be eating a varied, plant-rich diet, not too much, and quenching our thirst with water,” she concluded.

The study was funded by the Lundbeck Foundation, the Danish Heart Foundation, and the Leducq Foundation. The authors, editorialists, Ms. Parker, Dr. Cassidy, and Dr. Storey have reported no relevant financial relationships. Dr. Mellor has disclosed that he is a vegetarian.

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