Cardiology News

Do people who drink alcohol in moderation have a greater risk of early death than people who abstain? For years, a drink or two a day appeared to be linked to health benefits. But recently, scientists pointed out flaws in some of the studies that led to those conclusions, and public health warnings have escalated recently that there may be no safe level of alcohol consumption.

Now, yet another research analysis points toward that newer conclusion – that people who drink moderately do not necessarily live longer than people who abstain. The latest results are important because the researchers delved deep into data about people who previously drank but later quit, possibly due to health problems.

“That makes people who continue to drink look much healthier by comparison,” said Tim Stockwell, PhD, lead author of this latest analysis and a scientist with the Canadian Institute for Substance Use Research at the University of Victoria, in a statement.

The findings were published in the Journal of Studies on Alcohol and Drugs.

The key to their conclusion that drinking isn’t linked to longer life is based yet again on who moderate drinkers are compared to, Dr. Stockwell and his colleagues wrote.

For the study, researchers defined “low volume drinking” as having between one drink per week and up to two drinks per day. When researchers carefully excluded people who were former drinkers and only included data for people who were younger than 55 when they joined research studies, the abstainers and low-volume drinkers had similar risks of early death. But when the former drinkers were included in the abstainer group, the low-volume drinkers appeared to have a reduced risk of death.

When researchers define which people are included in a research analysis based on criteria that don’t reflect subtle but important population characteristics, the problem is called “selection bias.” 

“Studies with life-time selection biases may create misleading positive health associations. These biases pervade the field of alcohol epidemiology and can confuse communications about health risks,” the authors concluded.

They called for improvements in future research studies to better evaluate drinking levels that may influence health outcomes, and also noted one of their exploratory analyses suggested a need to delve deeper into the effects of other outside variables such as smoking and socioeconomic status. 
 

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

Do people who drink alcohol in moderation have a greater risk of early death than people who abstain? For years, a drink or two a day appeared to be linked to health benefits. But recently, scientists pointed out flaws in some of the studies that led to those conclusions, and public health warnings have escalated recently that there may be no safe level of alcohol consumption.

Now, yet another research analysis points toward that newer conclusion – that people who drink moderately do not necessarily live longer than people who abstain. The latest results are important because the researchers delved deep into data about people who previously drank but later quit, possibly due to health problems.

“That makes people who continue to drink look much healthier by comparison,” said Tim Stockwell, PhD, lead author of this latest analysis and a scientist with the Canadian Institute for Substance Use Research at the University of Victoria, in a statement.

The findings were published in the Journal of Studies on Alcohol and Drugs.

The key to their conclusion that drinking isn’t linked to longer life is based yet again on who moderate drinkers are compared to, Dr. Stockwell and his colleagues wrote.

For the study, researchers defined “low volume drinking” as having between one drink per week and up to two drinks per day. When researchers carefully excluded people who were former drinkers and only included data for people who were younger than 55 when they joined research studies, the abstainers and low-volume drinkers had similar risks of early death. But when the former drinkers were included in the abstainer group, the low-volume drinkers appeared to have a reduced risk of death.

When researchers define which people are included in a research analysis based on criteria that don’t reflect subtle but important population characteristics, the problem is called “selection bias.” 

“Studies with life-time selection biases may create misleading positive health associations. These biases pervade the field of alcohol epidemiology and can confuse communications about health risks,” the authors concluded.

They called for improvements in future research studies to better evaluate drinking levels that may influence health outcomes, and also noted one of their exploratory analyses suggested a need to delve deeper into the effects of other outside variables such as smoking and socioeconomic status. 
 

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

Do people who drink alcohol in moderation have a greater risk of early death than people who abstain? For years, a drink or two a day appeared to be linked to health benefits. But recently, scientists pointed out flaws in some of the studies that led to those conclusions, and public health warnings have escalated recently that there may be no safe level of alcohol consumption.

Now, yet another research analysis points toward that newer conclusion – that people who drink moderately do not necessarily live longer than people who abstain. The latest results are important because the researchers delved deep into data about people who previously drank but later quit, possibly due to health problems.

“That makes people who continue to drink look much healthier by comparison,” said Tim Stockwell, PhD, lead author of this latest analysis and a scientist with the Canadian Institute for Substance Use Research at the University of Victoria, in a statement.

The findings were published in the Journal of Studies on Alcohol and Drugs.

The key to their conclusion that drinking isn’t linked to longer life is based yet again on who moderate drinkers are compared to, Dr. Stockwell and his colleagues wrote.

For the study, researchers defined “low volume drinking” as having between one drink per week and up to two drinks per day. When researchers carefully excluded people who were former drinkers and only included data for people who were younger than 55 when they joined research studies, the abstainers and low-volume drinkers had similar risks of early death. But when the former drinkers were included in the abstainer group, the low-volume drinkers appeared to have a reduced risk of death.

When researchers define which people are included in a research analysis based on criteria that don’t reflect subtle but important population characteristics, the problem is called “selection bias.” 

“Studies with life-time selection biases may create misleading positive health associations. These biases pervade the field of alcohol epidemiology and can confuse communications about health risks,” the authors concluded.

They called for improvements in future research studies to better evaluate drinking levels that may influence health outcomes, and also noted one of their exploratory analyses suggested a need to delve deeper into the effects of other outside variables such as smoking and socioeconomic status. 
 

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

“We really aren’t taking care of records — we’re taking care of people.” — Dr. Lawrence Weed

What is the purpose of a progress note? Anyone? Yes, you there. “Insurance billing?” Yes, that’s a good one. Anyone else? “To remember what you did?” Excellent. Another? Yes, that’s right, for others to follow along in your care. These are all good reasons for a progress note to exist. But they aren’t the whole story. Let’s start at the beginning.

Charts were once a collection of paper sheets with handwritten notes. Sometimes illegible, sometimes beautiful, always efficient. A progress note back then could be just 10 characters, AK, LN2, X,X,X,X,X (with X’s marking nitrogen sprays). Then came the healthcare K-Pg event: the conversion to EMRs. Those doctors who survived evolved into computer programmers, creating blocks of text from a few keystrokes. But like toddler-sized Legos, the blocks made it impossible to build a note that is nuanced or precise. Worse yet, many notes consisting of blocks from one note added awkwardly to a new note, creating grotesque structures unrecognizable as anything that should exist in nature. Words and numbers, but no information.

Newtown grafitti / flickr / CC BY-2.0

Thanks to the eternity of EMR, these creations live on, hideous and useless. They waste not only the server’s energy but also our time. Few things are more maddening than scrolling to reach the bottom of another physician’s note only to find there is nothing there.

Whose fault is this? Anyone? Yes, that’s right, insurers. As there are probably no payers in this audience, let’s blame them. I agree, the crushing burden of documentation-to-get-reimbursed has forced us to create “notes” that add no value to us but add up points for us to get paid for them. CMS, payers, prior authorizations, and now even patients, it seems we are documenting for lots of people except for us. There isn’t time to satisfy all and this significant burden for every encounter is a proximate cause for doctors despair. Until now.

In 2024, came our story’s deus ex machina: the AI scribe. A tool that can listen to a doctor visit, then from the ether, generate a note. A fully formed, comprehensive, sometimes pretty note that satisfies all audiences. Dr. Larry Weed must be dancing in heaven. It was Dr. Weed who led us from the nicotine-stained logs of the 1950s to the powerful problem-based notes we use today, an innovation that rivals the stethoscope in its impact.

Professor Weed also predicted that computers would be important to capture and make sense of patient data, helping us make accurate diagnoses and efficient plans. Again, he was right. He would surely be advocating to take advantage of AI scribes’ marvelous ability to capture salient data and present it in the form of a problem-oriented medical record.

AI scribes will be ubiquitous soon; I’m fast and even for me they save time. They also allow, for the first time in a decade, to turn from the glow of a screen to actually face the patient – we no longer have to scribe and care simultaneously. Hallelujah. And yet, lest I disappoint you without a twist, it seems with AI scribes, like EMRs we lose a little something too.

Like self-driving cars or ChatGPT-generated letters, they remove cognitive loads. They are lovely when you have to multitask or are trying to recall a visit from hours (days) ago. Using them, you’ll feel faster, lighter, freer, happier. But what’s missing is the thinking. At the end, you have an exquisite note, but you didn’t write it. It has the salient points, but none of the mental work to create it. AI scribes subvert the valuable work of synthesis. That was the critical part of Dr. Weed’s discovery: writing problem-oriented notes helped us think better.

Kaiser Permanente

Writing allows for the friction that helps us process what is going on with a patient. It allows for the discovery of diagnoses and prompts plans. When I was an intern, one of my attendings would hand write notes, succinctly showing what he had observed and was thinking. He’d sketch diagrams in the chart, for example, to help illustrate how we’d work though the toxic, metabolic, and infectious etiologies of acute liver failure. Sublime.

The act of writing also helps remind us there is a person attached to these words. Like a handwritten sympathy card, it is intimate, human. Even using our EMR, I’d still often type sentences that help tell the patient’s story. “Her sister just died. Utterly devastated. I’ll forward chart to Bob (her PCP) to check in on her.” Or: “Scratch golfer wants to know why he is getting so many SCCs now. ‘Like bankruptcy, gradually then suddenly,’ I explained. I think I broke through.”

Since we’ve concluded the purpose of a note is mostly to capture data, AI scribes are a godsend. They do so with remarkable quality and efficiency. We’ll just have to remember if the diagnosis is unclear, then it might help to write the note out yourself. And even when done by the AI machine, we might add human touches now and again lest there be no art left in what we do.

“For sale. Sun hat. Never worn.”

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on X. Write to him at dermnews@mdedge.com.

“We really aren’t taking care of records — we’re taking care of people.” — Dr. Lawrence Weed

What is the purpose of a progress note? Anyone? Yes, you there. “Insurance billing?” Yes, that’s a good one. Anyone else? “To remember what you did?” Excellent. Another? Yes, that’s right, for others to follow along in your care. These are all good reasons for a progress note to exist. But they aren’t the whole story. Let’s start at the beginning.

Charts were once a collection of paper sheets with handwritten notes. Sometimes illegible, sometimes beautiful, always efficient. A progress note back then could be just 10 characters, AK, LN2, X,X,X,X,X (with X’s marking nitrogen sprays). Then came the healthcare K-Pg event: the conversion to EMRs. Those doctors who survived evolved into computer programmers, creating blocks of text from a few keystrokes. But like toddler-sized Legos, the blocks made it impossible to build a note that is nuanced or precise. Worse yet, many notes consisting of blocks from one note added awkwardly to a new note, creating grotesque structures unrecognizable as anything that should exist in nature. Words and numbers, but no information.

Newtown grafitti / flickr / CC BY-2.0

Thanks to the eternity of EMR, these creations live on, hideous and useless. They waste not only the server’s energy but also our time. Few things are more maddening than scrolling to reach the bottom of another physician’s note only to find there is nothing there.

Whose fault is this? Anyone? Yes, that’s right, insurers. As there are probably no payers in this audience, let’s blame them. I agree, the crushing burden of documentation-to-get-reimbursed has forced us to create “notes” that add no value to us but add up points for us to get paid for them. CMS, payers, prior authorizations, and now even patients, it seems we are documenting for lots of people except for us. There isn’t time to satisfy all and this significant burden for every encounter is a proximate cause for doctors despair. Until now.

In 2024, came our story’s deus ex machina: the AI scribe. A tool that can listen to a doctor visit, then from the ether, generate a note. A fully formed, comprehensive, sometimes pretty note that satisfies all audiences. Dr. Larry Weed must be dancing in heaven. It was Dr. Weed who led us from the nicotine-stained logs of the 1950s to the powerful problem-based notes we use today, an innovation that rivals the stethoscope in its impact.

Professor Weed also predicted that computers would be important to capture and make sense of patient data, helping us make accurate diagnoses and efficient plans. Again, he was right. He would surely be advocating to take advantage of AI scribes’ marvelous ability to capture salient data and present it in the form of a problem-oriented medical record.

AI scribes will be ubiquitous soon; I’m fast and even for me they save time. They also allow, for the first time in a decade, to turn from the glow of a screen to actually face the patient – we no longer have to scribe and care simultaneously. Hallelujah. And yet, lest I disappoint you without a twist, it seems with AI scribes, like EMRs we lose a little something too.

Like self-driving cars or ChatGPT-generated letters, they remove cognitive loads. They are lovely when you have to multitask or are trying to recall a visit from hours (days) ago. Using them, you’ll feel faster, lighter, freer, happier. But what’s missing is the thinking. At the end, you have an exquisite note, but you didn’t write it. It has the salient points, but none of the mental work to create it. AI scribes subvert the valuable work of synthesis. That was the critical part of Dr. Weed’s discovery: writing problem-oriented notes helped us think better.

Kaiser Permanente

Writing allows for the friction that helps us process what is going on with a patient. It allows for the discovery of diagnoses and prompts plans. When I was an intern, one of my attendings would hand write notes, succinctly showing what he had observed and was thinking. He’d sketch diagrams in the chart, for example, to help illustrate how we’d work though the toxic, metabolic, and infectious etiologies of acute liver failure. Sublime.

The act of writing also helps remind us there is a person attached to these words. Like a handwritten sympathy card, it is intimate, human. Even using our EMR, I’d still often type sentences that help tell the patient’s story. “Her sister just died. Utterly devastated. I’ll forward chart to Bob (her PCP) to check in on her.” Or: “Scratch golfer wants to know why he is getting so many SCCs now. ‘Like bankruptcy, gradually then suddenly,’ I explained. I think I broke through.”

Since we’ve concluded the purpose of a note is mostly to capture data, AI scribes are a godsend. They do so with remarkable quality and efficiency. We’ll just have to remember if the diagnosis is unclear, then it might help to write the note out yourself. And even when done by the AI machine, we might add human touches now and again lest there be no art left in what we do.

“For sale. Sun hat. Never worn.”

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on X. Write to him at dermnews@mdedge.com.

“We really aren’t taking care of records — we’re taking care of people.” — Dr. Lawrence Weed

What is the purpose of a progress note? Anyone? Yes, you there. “Insurance billing?” Yes, that’s a good one. Anyone else? “To remember what you did?” Excellent. Another? Yes, that’s right, for others to follow along in your care. These are all good reasons for a progress note to exist. But they aren’t the whole story. Let’s start at the beginning.

Charts were once a collection of paper sheets with handwritten notes. Sometimes illegible, sometimes beautiful, always efficient. A progress note back then could be just 10 characters, AK, LN2, X,X,X,X,X (with X’s marking nitrogen sprays). Then came the healthcare K-Pg event: the conversion to EMRs. Those doctors who survived evolved into computer programmers, creating blocks of text from a few keystrokes. But like toddler-sized Legos, the blocks made it impossible to build a note that is nuanced or precise. Worse yet, many notes consisting of blocks from one note added awkwardly to a new note, creating grotesque structures unrecognizable as anything that should exist in nature. Words and numbers, but no information.

Newtown grafitti / flickr / CC BY-2.0

Thanks to the eternity of EMR, these creations live on, hideous and useless. They waste not only the server’s energy but also our time. Few things are more maddening than scrolling to reach the bottom of another physician’s note only to find there is nothing there.

Whose fault is this? Anyone? Yes, that’s right, insurers. As there are probably no payers in this audience, let’s blame them. I agree, the crushing burden of documentation-to-get-reimbursed has forced us to create “notes” that add no value to us but add up points for us to get paid for them. CMS, payers, prior authorizations, and now even patients, it seems we are documenting for lots of people except for us. There isn’t time to satisfy all and this significant burden for every encounter is a proximate cause for doctors despair. Until now.

In 2024, came our story’s deus ex machina: the AI scribe. A tool that can listen to a doctor visit, then from the ether, generate a note. A fully formed, comprehensive, sometimes pretty note that satisfies all audiences. Dr. Larry Weed must be dancing in heaven. It was Dr. Weed who led us from the nicotine-stained logs of the 1950s to the powerful problem-based notes we use today, an innovation that rivals the stethoscope in its impact.

Professor Weed also predicted that computers would be important to capture and make sense of patient data, helping us make accurate diagnoses and efficient plans. Again, he was right. He would surely be advocating to take advantage of AI scribes’ marvelous ability to capture salient data and present it in the form of a problem-oriented medical record.

AI scribes will be ubiquitous soon; I’m fast and even for me they save time. They also allow, for the first time in a decade, to turn from the glow of a screen to actually face the patient – we no longer have to scribe and care simultaneously. Hallelujah. And yet, lest I disappoint you without a twist, it seems with AI scribes, like EMRs we lose a little something too.

Like self-driving cars or ChatGPT-generated letters, they remove cognitive loads. They are lovely when you have to multitask or are trying to recall a visit from hours (days) ago. Using them, you’ll feel faster, lighter, freer, happier. But what’s missing is the thinking. At the end, you have an exquisite note, but you didn’t write it. It has the salient points, but none of the mental work to create it. AI scribes subvert the valuable work of synthesis. That was the critical part of Dr. Weed’s discovery: writing problem-oriented notes helped us think better.

Kaiser Permanente

Writing allows for the friction that helps us process what is going on with a patient. It allows for the discovery of diagnoses and prompts plans. When I was an intern, one of my attendings would hand write notes, succinctly showing what he had observed and was thinking. He’d sketch diagrams in the chart, for example, to help illustrate how we’d work though the toxic, metabolic, and infectious etiologies of acute liver failure. Sublime.

The act of writing also helps remind us there is a person attached to these words. Like a handwritten sympathy card, it is intimate, human. Even using our EMR, I’d still often type sentences that help tell the patient’s story. “Her sister just died. Utterly devastated. I’ll forward chart to Bob (her PCP) to check in on her.” Or: “Scratch golfer wants to know why he is getting so many SCCs now. ‘Like bankruptcy, gradually then suddenly,’ I explained. I think I broke through.”

Since we’ve concluded the purpose of a note is mostly to capture data, AI scribes are a godsend. They do so with remarkable quality and efficiency. We’ll just have to remember if the diagnosis is unclear, then it might help to write the note out yourself. And even when done by the AI machine, we might add human touches now and again lest there be no art left in what we do.

“For sale. Sun hat. Never worn.”

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on X. Write to him at dermnews@mdedge.com.

The market for proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors to lower cholesterol is taking off with several new drugs being introduced or nearing the market, which will increase competition and enable more patients to reach low-density lipoprotein (LDL) goals, experts said.

One new anti-PCSK9 agent — lerodalcibep from LIB Therapeutics — is a small protein molecule, which is expected to reach the market by early 2026. It is being positioned as a step forward from the two monoclonal antibody products already available — evolocumab (Repatha; Amgen) and alirocumab (Praluent; Sanofi/Regeneron).

The new option can be given less frequently than the antibodies with a once-a-month injection instead of every 2 weeks. It also does not need to be kept refrigerated like the antibodies, Evan Stein, MD, chief scientific and operating officer of LIB Therapeutics, said in an interview.

Two phase 3 trials have recently been reported, showing impressive reductions in LDL in patients already taking statins.
 

The LIBerate Trials

The LIBerate-HR trial, published in JAMA Cardiology, involved 922 patients who still had LDL above target despite taking maximally tolerated statin therapy plus other lipid-lowering agents in some cases.

The trial found a time-averaged mean reduction in LDL cholesterol of 62%.

“This large reduction resulted in more than 90% of patients reaching the new lower LDL targets set in recent guidelines of less than 55 mg/dL for patients with cardiovascular disease or at very high risk, and less than 70 mg/dL in patients at risk,” said Stein.

Another phase 3 trial, LIBerate-CVD, has also shown reductions in LDL cholesterol levels of more than 60% in patients at high risk for cardiovascular disease on maximally tolerated statins.

LIB Therapeutics plans to file approval applications for lerodalcibep in the United States and Europe later this year.
 

A Crowded Field

Dr. Stein said PCSK9 inhibitors have been underused so far, but this is starting to change.

“The monoclonal antibodies were way overpriced costing around $14,000 per year when they were first introduced, which resulted in huge pushback from insurance companies,” Dr. Stein said, which made the drugs difficult to prescribe. “Then a few years ago, the price dropped a bit, and now they’re probably running at about $4000 per year, which made them more accessible.”

He said the market is now rapidly taking off. Lerodalcibep will compete in the anti-PCSK9 market with not only the two monoclonal antibodies but also with the new short-interfering RNA agent, inclisiran (Leqvio; Novartis) , a novel injectable agent that is given just twice a year but has to be administered at a medical facility.

Despite the crowded field, there appears to be plenty of room in the market. “Last year, growth was just under 40%. The first quarter of this year, it has increased by 44%. While the introduction of inclisiran has added to this growth, it hasn’t dented the sales of the existing monoclonal antibodies,” said Dr. Stein.

He estimates that the anti-PCSK9 market will reach $3 billion globally this year, and by the time lerodalcibep is launched, it could be worth $5 billion.

As well as inclisiran and lerodalcibep, there are other innovations in the anti-PCSK9 field in development, with oral drugs now also in the pipeline. The first one of these, in development by Merck, is in early phase 3 trials, and AstraZeneca has an oral agent in earlier development.
 

Enthusiastic Response

Other experts in the lipid field are also enthusiastic about new developments in the PCSK9s.

Jorge Plutzky, MD, director of preventive cardiology at Brigham and Women’s Hospital in Boston, said he welcomes the prospect of new approaches to PCSK9 inhibition.

“The increase in the number of safe, effective tools for LDL lowering, whether through PCSK9 or other targets, is inevitably beneficial for patients and the field,” he said during an interview.

Dr. Plutzky pointed out that although the current agents are effective, cost and coverage remain issues despite some recent progress in these areas, and new agents will increase competition and should hopefully drive prices down. Having a variety of dosing methods and frequencies provides more options for patients to find the one that works best for them.

Lerodalcibep’s once-monthly dosing schedule and the lack of need for refrigeration may be appreciated by some patients, he said, particularly those who need to travel for long periods.

Connie Newman, MD, adjunct professor of medicine at NYU School of Medicine, New York City, said there is plenty of room in the market to accommodate patient’s needs and preferences.

“Despite the US FDA approval of three medications that target PCSK9, there is a need for more anti-PCSK9 agents that reduce LDL and cardiovascular events,” she said. “In the US alone, 25% of adults have LDL levels of 130 mg/dL and above. Of all the non-statin therapies, medications targeting PCSK9 produce the greatest reduction in LDL. However, some patients may not tolerate one or more of the medications available or may prefer a monthly injection of lower volume.”

Dr. Newman said she believes there will still be a market for injectable formulations of PCSK9 inhibitors in the future, even if oral formulations are approved.

“Oral formulations usually require more frequent administration. Some people prefer longer-acting medications that can be taken less often. This might lead to better adherence,” she said.

Dr. Stein said he agrees there will always be room for different options. “And you only have to look at what is happening with the weight loss drugs to see that there is a market for injectables.” The ability to get patients to the new, more aggressive LDL goals is what is important, he added. “These drugs do that, and offering patients a choice of agents and delivery mechanisms is helpful.”

A version of this article appeared on Medscape.com.

The market for proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors to lower cholesterol is taking off with several new drugs being introduced or nearing the market, which will increase competition and enable more patients to reach low-density lipoprotein (LDL) goals, experts said.

One new anti-PCSK9 agent — lerodalcibep from LIB Therapeutics — is a small protein molecule, which is expected to reach the market by early 2026. It is being positioned as a step forward from the two monoclonal antibody products already available — evolocumab (Repatha; Amgen) and alirocumab (Praluent; Sanofi/Regeneron).

The new option can be given less frequently than the antibodies with a once-a-month injection instead of every 2 weeks. It also does not need to be kept refrigerated like the antibodies, Evan Stein, MD, chief scientific and operating officer of LIB Therapeutics, said in an interview.

Two phase 3 trials have recently been reported, showing impressive reductions in LDL in patients already taking statins.
 

The LIBerate Trials

The LIBerate-HR trial, published in JAMA Cardiology, involved 922 patients who still had LDL above target despite taking maximally tolerated statin therapy plus other lipid-lowering agents in some cases.

The trial found a time-averaged mean reduction in LDL cholesterol of 62%.

“This large reduction resulted in more than 90% of patients reaching the new lower LDL targets set in recent guidelines of less than 55 mg/dL for patients with cardiovascular disease or at very high risk, and less than 70 mg/dL in patients at risk,” said Stein.

Another phase 3 trial, LIBerate-CVD, has also shown reductions in LDL cholesterol levels of more than 60% in patients at high risk for cardiovascular disease on maximally tolerated statins.

LIB Therapeutics plans to file approval applications for lerodalcibep in the United States and Europe later this year.
 

A Crowded Field

Dr. Stein said PCSK9 inhibitors have been underused so far, but this is starting to change.

“The monoclonal antibodies were way overpriced costing around $14,000 per year when they were first introduced, which resulted in huge pushback from insurance companies,” Dr. Stein said, which made the drugs difficult to prescribe. “Then a few years ago, the price dropped a bit, and now they’re probably running at about $4000 per year, which made them more accessible.”

He said the market is now rapidly taking off. Lerodalcibep will compete in the anti-PCSK9 market with not only the two monoclonal antibodies but also with the new short-interfering RNA agent, inclisiran (Leqvio; Novartis) , a novel injectable agent that is given just twice a year but has to be administered at a medical facility.

Despite the crowded field, there appears to be plenty of room in the market. “Last year, growth was just under 40%. The first quarter of this year, it has increased by 44%. While the introduction of inclisiran has added to this growth, it hasn’t dented the sales of the existing monoclonal antibodies,” said Dr. Stein.

He estimates that the anti-PCSK9 market will reach $3 billion globally this year, and by the time lerodalcibep is launched, it could be worth $5 billion.

As well as inclisiran and lerodalcibep, there are other innovations in the anti-PCSK9 field in development, with oral drugs now also in the pipeline. The first one of these, in development by Merck, is in early phase 3 trials, and AstraZeneca has an oral agent in earlier development.
 

Enthusiastic Response

Other experts in the lipid field are also enthusiastic about new developments in the PCSK9s.

Jorge Plutzky, MD, director of preventive cardiology at Brigham and Women’s Hospital in Boston, said he welcomes the prospect of new approaches to PCSK9 inhibition.

“The increase in the number of safe, effective tools for LDL lowering, whether through PCSK9 or other targets, is inevitably beneficial for patients and the field,” he said during an interview.

Dr. Plutzky pointed out that although the current agents are effective, cost and coverage remain issues despite some recent progress in these areas, and new agents will increase competition and should hopefully drive prices down. Having a variety of dosing methods and frequencies provides more options for patients to find the one that works best for them.

Lerodalcibep’s once-monthly dosing schedule and the lack of need for refrigeration may be appreciated by some patients, he said, particularly those who need to travel for long periods.

Connie Newman, MD, adjunct professor of medicine at NYU School of Medicine, New York City, said there is plenty of room in the market to accommodate patient’s needs and preferences.

“Despite the US FDA approval of three medications that target PCSK9, there is a need for more anti-PCSK9 agents that reduce LDL and cardiovascular events,” she said. “In the US alone, 25% of adults have LDL levels of 130 mg/dL and above. Of all the non-statin therapies, medications targeting PCSK9 produce the greatest reduction in LDL. However, some patients may not tolerate one or more of the medications available or may prefer a monthly injection of lower volume.”

Dr. Newman said she believes there will still be a market for injectable formulations of PCSK9 inhibitors in the future, even if oral formulations are approved.

“Oral formulations usually require more frequent administration. Some people prefer longer-acting medications that can be taken less often. This might lead to better adherence,” she said.

Dr. Stein said he agrees there will always be room for different options. “And you only have to look at what is happening with the weight loss drugs to see that there is a market for injectables.” The ability to get patients to the new, more aggressive LDL goals is what is important, he added. “These drugs do that, and offering patients a choice of agents and delivery mechanisms is helpful.”

A version of this article appeared on Medscape.com.

The market for proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors to lower cholesterol is taking off with several new drugs being introduced or nearing the market, which will increase competition and enable more patients to reach low-density lipoprotein (LDL) goals, experts said.

One new anti-PCSK9 agent — lerodalcibep from LIB Therapeutics — is a small protein molecule, which is expected to reach the market by early 2026. It is being positioned as a step forward from the two monoclonal antibody products already available — evolocumab (Repatha; Amgen) and alirocumab (Praluent; Sanofi/Regeneron).

The new option can be given less frequently than the antibodies with a once-a-month injection instead of every 2 weeks. It also does not need to be kept refrigerated like the antibodies, Evan Stein, MD, chief scientific and operating officer of LIB Therapeutics, said in an interview.

Two phase 3 trials have recently been reported, showing impressive reductions in LDL in patients already taking statins.
 

The LIBerate Trials

The LIBerate-HR trial, published in JAMA Cardiology, involved 922 patients who still had LDL above target despite taking maximally tolerated statin therapy plus other lipid-lowering agents in some cases.

The trial found a time-averaged mean reduction in LDL cholesterol of 62%.

“This large reduction resulted in more than 90% of patients reaching the new lower LDL targets set in recent guidelines of less than 55 mg/dL for patients with cardiovascular disease or at very high risk, and less than 70 mg/dL in patients at risk,” said Stein.

Another phase 3 trial, LIBerate-CVD, has also shown reductions in LDL cholesterol levels of more than 60% in patients at high risk for cardiovascular disease on maximally tolerated statins.

LIB Therapeutics plans to file approval applications for lerodalcibep in the United States and Europe later this year.
 

A Crowded Field

Dr. Stein said PCSK9 inhibitors have been underused so far, but this is starting to change.

“The monoclonal antibodies were way overpriced costing around $14,000 per year when they were first introduced, which resulted in huge pushback from insurance companies,” Dr. Stein said, which made the drugs difficult to prescribe. “Then a few years ago, the price dropped a bit, and now they’re probably running at about $4000 per year, which made them more accessible.”

He said the market is now rapidly taking off. Lerodalcibep will compete in the anti-PCSK9 market with not only the two monoclonal antibodies but also with the new short-interfering RNA agent, inclisiran (Leqvio; Novartis) , a novel injectable agent that is given just twice a year but has to be administered at a medical facility.

Despite the crowded field, there appears to be plenty of room in the market. “Last year, growth was just under 40%. The first quarter of this year, it has increased by 44%. While the introduction of inclisiran has added to this growth, it hasn’t dented the sales of the existing monoclonal antibodies,” said Dr. Stein.

He estimates that the anti-PCSK9 market will reach $3 billion globally this year, and by the time lerodalcibep is launched, it could be worth $5 billion.

As well as inclisiran and lerodalcibep, there are other innovations in the anti-PCSK9 field in development, with oral drugs now also in the pipeline. The first one of these, in development by Merck, is in early phase 3 trials, and AstraZeneca has an oral agent in earlier development.
 

Enthusiastic Response

Other experts in the lipid field are also enthusiastic about new developments in the PCSK9s.

Jorge Plutzky, MD, director of preventive cardiology at Brigham and Women’s Hospital in Boston, said he welcomes the prospect of new approaches to PCSK9 inhibition.

“The increase in the number of safe, effective tools for LDL lowering, whether through PCSK9 or other targets, is inevitably beneficial for patients and the field,” he said during an interview.

Dr. Plutzky pointed out that although the current agents are effective, cost and coverage remain issues despite some recent progress in these areas, and new agents will increase competition and should hopefully drive prices down. Having a variety of dosing methods and frequencies provides more options for patients to find the one that works best for them.

Lerodalcibep’s once-monthly dosing schedule and the lack of need for refrigeration may be appreciated by some patients, he said, particularly those who need to travel for long periods.

Connie Newman, MD, adjunct professor of medicine at NYU School of Medicine, New York City, said there is plenty of room in the market to accommodate patient’s needs and preferences.

“Despite the US FDA approval of three medications that target PCSK9, there is a need for more anti-PCSK9 agents that reduce LDL and cardiovascular events,” she said. “In the US alone, 25% of adults have LDL levels of 130 mg/dL and above. Of all the non-statin therapies, medications targeting PCSK9 produce the greatest reduction in LDL. However, some patients may not tolerate one or more of the medications available or may prefer a monthly injection of lower volume.”

Dr. Newman said she believes there will still be a market for injectable formulations of PCSK9 inhibitors in the future, even if oral formulations are approved.

“Oral formulations usually require more frequent administration. Some people prefer longer-acting medications that can be taken less often. This might lead to better adherence,” she said.

Dr. Stein said he agrees there will always be room for different options. “And you only have to look at what is happening with the weight loss drugs to see that there is a market for injectables.” The ability to get patients to the new, more aggressive LDL goals is what is important, he added. “These drugs do that, and offering patients a choice of agents and delivery mechanisms is helpful.”

A version of this article appeared on Medscape.com.

Compared with traditional replacement valves, sutureless valves placed through minimally invasive cardiac surgery have less data supporting their use but offer unique features that might make them the preferred option for certain patients, reported specialists.

Two valves placed by minimally invasive surgery received regulatory approval 8 years ago, but they are not widely used to this day.

The sutureless device known as Perceval (Corcym) and a rapidly deployed device called Intuity (Edwards Lifesciences) are used as an alternative to surgical aortic valve replacement (SAVR) and transcatheter aortic valve replacement (TAVR). But despite being commercially available since 2016, the devices are still not being used much.

The devices are not discussed in substantial detail in either the joint guidelines from the American College of Cardiology and American Heart Association issued in 2020 or guidelines from the European Society of Cardiology issued in 2022.

Cristiano Spadaccio, MD, PhD, a cardiothoracic surgeon associated with Lancashire Cardiac Centre in Blackpool, England, and his colleagues reviewed the small number of studies evaluating the alternate approach to “make the cardiology world aware” of alternatives “that can relieve the surgical burden by minimizing the implantation time and length of the operation,” he said.

The comprehensive review is published in the Journal of the American College of Cardiology.
 

A Neglected Alternative

The sutureless Perceval device is held in place by a stent frame that self-expands. The Intuity device also relies primarily on its framework to anchor the valve in place but does involve three sutures. Both devices are still referred to as sutureless in the new review of them.

Only a small number of centers perform minimally invasive cardiac surgeries, and the main advantage of the devices — rapid deployment — has been eroded with the advent of automated knotting which has significantly reduced the time to implant and sutured valve.

The underuse of these devices is largely caused by the limited amount of comparative and prospective data, said Dr. Spadaccio. “The entire literature on sutureless aortic valve replacement with the exception of one randomized controlled trial is observational.”

That trial, PERSIST-AVR, found that the sutureless valves were just as good as conventional ones when it comes to major adverse cardiovascular events including all-cause death, myocardial infarction, stroke, or valve reintervention at 1 year.

In a subanalysis limited to patients who had isolated aortic valve replacement, the sutureless procedure was associated with lower adverse events (5.2% vs 10.8%) at the cost of a higher rate of pacemaker implantation (11% vs 1.6%).

There are also multiple retrospective studies and registries that have generated observational data comparing sutureless aortic valve replacement with SAVR and TAVR in various patient populations, said Dr. Spadaccio, and the review was based on more than a dozen studies published since 2015. Long-term follow-up data for sutureless aortic valve replacements, which now exceeds 10 years, suggest rates of structural valve deterioration and reintervention have been acceptably low.

The minimally invasive procedures have other advantages too. For example, relative to the greater trauma associated with open heart surgery, minimally invasive surgeries typically involve faster recovery, an advantage likely to appeal to many patients who are candidates for either.
 

Quicker Recovery

Collectively, these data suggest that sutureless aortic valve replacement might be a reasonable or even a more appropriate alternative to either SAVR or TAVR when considering specific patient characteristics and goals, according to the review, which included an algorithm identifying specifically where sutureless aortic valve replacement fits with SAVR and TAVR.

“The algorithm is based on different clinical scenarios and reflects current guidelines for SAVR,” said Dr. Spadaccio. For example, current guidelines identify SAVR as preferred in patients younger than 65 years and in older patients with a low Society of Thoracic Surgeons (STS) score, but there are many instances in which sutureless aortic valve replacement might be more attractive, such as in those also undergoing mitral valve repair, coronary artery bypass grafting, or another surgical procedure.

Dr. Spadaccio said that the STS score should not be considered in isolation when evaluating a patient for SAVR or TAVR. Other features such as mobility, frailty score, and comorbid liver or renal disease should also be considered when discussing the three options with patients. As a result, the algorithm emphasizes a detailed evaluation of patient characteristics in selecting one procedure over another.

“The treatment should be really tailored on the individual patient basis,” said Dr. Spadaccio.

Dr. Spadaccio acknowledged that there is a need for more comparative trials, particularly in regard to sutureless aortic valve replacement as an alternative to TAVR. “I really think that a 1:1 RCT on sutureless aortic valve replacement vs TAVR could give better answers to all of these interrogatives.”

But despite the limitations outlined in this review, Dr. Spadaccio and colleagues challenged the perception that current data are not sufficient to allow clinicians to consider sutureless aortic valve replacement in the mix of options.
 

A Viable Option

This comprehensive summary of what is known about sutureless aortic valve replacement compared with the other options addresses an important knowledge gap, said S. Chris Malaisrie, MD, a cardiac surgeon at Northwestern University Feinberg School of Medicine, Chicago, Illinois.

He said he agrees this option has unique qualities. “Minimally invasive surgery has been largely ignored by guideline writers, but patients certainly demand options that are less invasive than standard open heart surgery. Sutureless and rapid deployment valves facilitate minimally invasive surgery and offer an advantageous option for younger patients.”

Dr. Malaisrie said the review is generating discussion about a potentially valuable option within the cardiology community. And that is exactly what Dr. Spadaccio was hoping for. “This paper was meant to educate as much as possible on these details to assist and inform decision-making,” he said.

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

Compared with traditional replacement valves, sutureless valves placed through minimally invasive cardiac surgery have less data supporting their use but offer unique features that might make them the preferred option for certain patients, reported specialists.

Two valves placed by minimally invasive surgery received regulatory approval 8 years ago, but they are not widely used to this day.

The sutureless device known as Perceval (Corcym) and a rapidly deployed device called Intuity (Edwards Lifesciences) are used as an alternative to surgical aortic valve replacement (SAVR) and transcatheter aortic valve replacement (TAVR). But despite being commercially available since 2016, the devices are still not being used much.

The devices are not discussed in substantial detail in either the joint guidelines from the American College of Cardiology and American Heart Association issued in 2020 or guidelines from the European Society of Cardiology issued in 2022.

Cristiano Spadaccio, MD, PhD, a cardiothoracic surgeon associated with Lancashire Cardiac Centre in Blackpool, England, and his colleagues reviewed the small number of studies evaluating the alternate approach to “make the cardiology world aware” of alternatives “that can relieve the surgical burden by minimizing the implantation time and length of the operation,” he said.

The comprehensive review is published in the Journal of the American College of Cardiology.
 

A Neglected Alternative

The sutureless Perceval device is held in place by a stent frame that self-expands. The Intuity device also relies primarily on its framework to anchor the valve in place but does involve three sutures. Both devices are still referred to as sutureless in the new review of them.

Only a small number of centers perform minimally invasive cardiac surgeries, and the main advantage of the devices — rapid deployment — has been eroded with the advent of automated knotting which has significantly reduced the time to implant and sutured valve.

The underuse of these devices is largely caused by the limited amount of comparative and prospective data, said Dr. Spadaccio. “The entire literature on sutureless aortic valve replacement with the exception of one randomized controlled trial is observational.”

That trial, PERSIST-AVR, found that the sutureless valves were just as good as conventional ones when it comes to major adverse cardiovascular events including all-cause death, myocardial infarction, stroke, or valve reintervention at 1 year.

In a subanalysis limited to patients who had isolated aortic valve replacement, the sutureless procedure was associated with lower adverse events (5.2% vs 10.8%) at the cost of a higher rate of pacemaker implantation (11% vs 1.6%).

There are also multiple retrospective studies and registries that have generated observational data comparing sutureless aortic valve replacement with SAVR and TAVR in various patient populations, said Dr. Spadaccio, and the review was based on more than a dozen studies published since 2015. Long-term follow-up data for sutureless aortic valve replacements, which now exceeds 10 years, suggest rates of structural valve deterioration and reintervention have been acceptably low.

The minimally invasive procedures have other advantages too. For example, relative to the greater trauma associated with open heart surgery, minimally invasive surgeries typically involve faster recovery, an advantage likely to appeal to many patients who are candidates for either.
 

Quicker Recovery

Collectively, these data suggest that sutureless aortic valve replacement might be a reasonable or even a more appropriate alternative to either SAVR or TAVR when considering specific patient characteristics and goals, according to the review, which included an algorithm identifying specifically where sutureless aortic valve replacement fits with SAVR and TAVR.

“The algorithm is based on different clinical scenarios and reflects current guidelines for SAVR,” said Dr. Spadaccio. For example, current guidelines identify SAVR as preferred in patients younger than 65 years and in older patients with a low Society of Thoracic Surgeons (STS) score, but there are many instances in which sutureless aortic valve replacement might be more attractive, such as in those also undergoing mitral valve repair, coronary artery bypass grafting, or another surgical procedure.

Dr. Spadaccio said that the STS score should not be considered in isolation when evaluating a patient for SAVR or TAVR. Other features such as mobility, frailty score, and comorbid liver or renal disease should also be considered when discussing the three options with patients. As a result, the algorithm emphasizes a detailed evaluation of patient characteristics in selecting one procedure over another.

“The treatment should be really tailored on the individual patient basis,” said Dr. Spadaccio.

Dr. Spadaccio acknowledged that there is a need for more comparative trials, particularly in regard to sutureless aortic valve replacement as an alternative to TAVR. “I really think that a 1:1 RCT on sutureless aortic valve replacement vs TAVR could give better answers to all of these interrogatives.”

But despite the limitations outlined in this review, Dr. Spadaccio and colleagues challenged the perception that current data are not sufficient to allow clinicians to consider sutureless aortic valve replacement in the mix of options.
 

A Viable Option

This comprehensive summary of what is known about sutureless aortic valve replacement compared with the other options addresses an important knowledge gap, said S. Chris Malaisrie, MD, a cardiac surgeon at Northwestern University Feinberg School of Medicine, Chicago, Illinois.

He said he agrees this option has unique qualities. “Minimally invasive surgery has been largely ignored by guideline writers, but patients certainly demand options that are less invasive than standard open heart surgery. Sutureless and rapid deployment valves facilitate minimally invasive surgery and offer an advantageous option for younger patients.”

Dr. Malaisrie said the review is generating discussion about a potentially valuable option within the cardiology community. And that is exactly what Dr. Spadaccio was hoping for. “This paper was meant to educate as much as possible on these details to assist and inform decision-making,” he said.

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

Compared with traditional replacement valves, sutureless valves placed through minimally invasive cardiac surgery have less data supporting their use but offer unique features that might make them the preferred option for certain patients, reported specialists.

Two valves placed by minimally invasive surgery received regulatory approval 8 years ago, but they are not widely used to this day.

The sutureless device known as Perceval (Corcym) and a rapidly deployed device called Intuity (Edwards Lifesciences) are used as an alternative to surgical aortic valve replacement (SAVR) and transcatheter aortic valve replacement (TAVR). But despite being commercially available since 2016, the devices are still not being used much.

The devices are not discussed in substantial detail in either the joint guidelines from the American College of Cardiology and American Heart Association issued in 2020 or guidelines from the European Society of Cardiology issued in 2022.

Cristiano Spadaccio, MD, PhD, a cardiothoracic surgeon associated with Lancashire Cardiac Centre in Blackpool, England, and his colleagues reviewed the small number of studies evaluating the alternate approach to “make the cardiology world aware” of alternatives “that can relieve the surgical burden by minimizing the implantation time and length of the operation,” he said.

The comprehensive review is published in the Journal of the American College of Cardiology.
 

A Neglected Alternative

The sutureless Perceval device is held in place by a stent frame that self-expands. The Intuity device also relies primarily on its framework to anchor the valve in place but does involve three sutures. Both devices are still referred to as sutureless in the new review of them.

Only a small number of centers perform minimally invasive cardiac surgeries, and the main advantage of the devices — rapid deployment — has been eroded with the advent of automated knotting which has significantly reduced the time to implant and sutured valve.

The underuse of these devices is largely caused by the limited amount of comparative and prospective data, said Dr. Spadaccio. “The entire literature on sutureless aortic valve replacement with the exception of one randomized controlled trial is observational.”

That trial, PERSIST-AVR, found that the sutureless valves were just as good as conventional ones when it comes to major adverse cardiovascular events including all-cause death, myocardial infarction, stroke, or valve reintervention at 1 year.

In a subanalysis limited to patients who had isolated aortic valve replacement, the sutureless procedure was associated with lower adverse events (5.2% vs 10.8%) at the cost of a higher rate of pacemaker implantation (11% vs 1.6%).

There are also multiple retrospective studies and registries that have generated observational data comparing sutureless aortic valve replacement with SAVR and TAVR in various patient populations, said Dr. Spadaccio, and the review was based on more than a dozen studies published since 2015. Long-term follow-up data for sutureless aortic valve replacements, which now exceeds 10 years, suggest rates of structural valve deterioration and reintervention have been acceptably low.

The minimally invasive procedures have other advantages too. For example, relative to the greater trauma associated with open heart surgery, minimally invasive surgeries typically involve faster recovery, an advantage likely to appeal to many patients who are candidates for either.
 

Quicker Recovery

Collectively, these data suggest that sutureless aortic valve replacement might be a reasonable or even a more appropriate alternative to either SAVR or TAVR when considering specific patient characteristics and goals, according to the review, which included an algorithm identifying specifically where sutureless aortic valve replacement fits with SAVR and TAVR.

“The algorithm is based on different clinical scenarios and reflects current guidelines for SAVR,” said Dr. Spadaccio. For example, current guidelines identify SAVR as preferred in patients younger than 65 years and in older patients with a low Society of Thoracic Surgeons (STS) score, but there are many instances in which sutureless aortic valve replacement might be more attractive, such as in those also undergoing mitral valve repair, coronary artery bypass grafting, or another surgical procedure.

Dr. Spadaccio said that the STS score should not be considered in isolation when evaluating a patient for SAVR or TAVR. Other features such as mobility, frailty score, and comorbid liver or renal disease should also be considered when discussing the three options with patients. As a result, the algorithm emphasizes a detailed evaluation of patient characteristics in selecting one procedure over another.

“The treatment should be really tailored on the individual patient basis,” said Dr. Spadaccio.

Dr. Spadaccio acknowledged that there is a need for more comparative trials, particularly in regard to sutureless aortic valve replacement as an alternative to TAVR. “I really think that a 1:1 RCT on sutureless aortic valve replacement vs TAVR could give better answers to all of these interrogatives.”

But despite the limitations outlined in this review, Dr. Spadaccio and colleagues challenged the perception that current data are not sufficient to allow clinicians to consider sutureless aortic valve replacement in the mix of options.
 

A Viable Option

This comprehensive summary of what is known about sutureless aortic valve replacement compared with the other options addresses an important knowledge gap, said S. Chris Malaisrie, MD, a cardiac surgeon at Northwestern University Feinberg School of Medicine, Chicago, Illinois.

He said he agrees this option has unique qualities. “Minimally invasive surgery has been largely ignored by guideline writers, but patients certainly demand options that are less invasive than standard open heart surgery. Sutureless and rapid deployment valves facilitate minimally invasive surgery and offer an advantageous option for younger patients.”

Dr. Malaisrie said the review is generating discussion about a potentially valuable option within the cardiology community. And that is exactly what Dr. Spadaccio was hoping for. “This paper was meant to educate as much as possible on these details to assist and inform decision-making,” he said.

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

High blood pressure is an established risk factor for neurodegeneration and cognitive decline. Long-standing evidence shows that treating hypertension can reduce its vascular consequences, but whether that is true for neurodegeneration is less clear.

Valentin Fuster, MD, president of Mount Sinai Fuster Heart Hospital in New York City, told this news organization. “There is no question in the literature that untreated high blood pressure may lead to dementia,” he said. “The open question is whether treating blood pressure is sufficient to decrease or stop the progress of dementia.”

Studies are mixed, but recent research suggests that addressing hypertension does affect the risk for dementia. A secondary analysis of the China Rural Hypertension Control Project reported at the American Heart Association (AHA) Scientific Sessions in 2023 but not yet published showed that the 4-year blood pressure–lowering program in adults aged 40 or older significantly reduced the risk for all-cause dementia and cognitive impairment.

Similarly, a post hoc analysis of the SPRINT MIND trial found that participants aged 50 or older who underwent intensive (< 120 mm Hg) vs standard (< 140 mm Hg) blood pressure lowering had a lower rate of probable dementia or mild cognitive impairment.

Other studies pointing to a benefit included a pooled individual participant analysis of five randomized controlled trials, which found class I evidence to support antihypertensive treatment to reduce the risk for incident dementia, and an earlier systematic review and meta-analysis of the association of blood pressure lowering with newly diagnosed dementia or cognitive impairment.
 

How It Might Work

Some possible mechanisms underlying the connection have emerged.

“Vascular disease caused by hypertension is clearly implicated in one form of dementia, called vascular cognitive impairment and dementia,” Andrew Moran, MD, PhD, associate professor of medicine at Columbia University Vagelos College of Physicians and Surgeons in New York City, told this news organization. “This category includes dementia following a stroke caused by uncontrolled hypertension.” 

“At the same time, we now know that hypertension and other vascular risk factors can also contribute, along with other factors, to developing Alzheimer dementia,” he said. “Even without causing clinically evident stroke, vascular disease from hypertension can lead to subtle damage to the brain via ischemia, microhemorrhage, and atrophy.”

“It is well known that hypertension affects the vasculature, and the vasculature of the brain is not spared,” agreed Eileen Handberg, PhD, ARNP, a member of the Hypertension Workgroup at the American College of Cardiology (ACC) and a professor of medicine and director of the Cardiovascular Clinical Trials Program in the University of Florida, Gainesville, Florida. “Combine this with other mechanisms like inflammation and endothelial dysfunction, and add amyloid accumulation, and there is a deterioration in vascular beds leading to decreased cerebral blood flow,” she said.

Treating hypertension likely helps lower dementia risk through “a combination of reduced risk of stroke and also benefits on blood flow, blood vessel health, and reduction in neurodegeneration,” suggested Mitchell S.V. Elkind, MD, chief clinical science officer and past president of the AHA and a professor of neurology and epidemiology at Columbia University Irving Medical Center in New York City. “Midlife blood pressure elevations are associated with deposition of amyloid in the brain, so controlling blood pressure may reduce amyloid deposits and neurodegeneration.”
 

Time in Range or Treat to Target?

With respect to dementia risk, does treating hypertension to a specific target make a difference, or is it the time spent in a healthy blood pressure range? 

“Observational studies and a post hoc analysis of the SPRINT MIND trial suggest that more time spent in a healthy blood pressure range or more stable blood pressure are associated with lower dementia risk,” Dr. Moran said. Citing results of the CHRC program and SPRINT MIND trial, he suggested that while a dose-response effect (the lower the blood pressure, the lower the dementia risk) hasn’t been definitively demonstrated, it is likely the case.

In his practice, Dr. Moran follows ACC/AHA guidelines and prescribes antihypertensives to get blood pressure below 130/80 mm Hg in individuals with hypertension who have other high-risk factors (cardiovascular disease, diabetes, chronic kidney disease, or high risk for these conditions). “The treatment rule for people with hypertension without these other risk factors is less clear — lowering blood pressure below 140/90 mm Hg is a must; I will discuss with patients whether to go lower than that.”

“The relative contributions of time in range versus treating to a target for blood pressure require further study,” said Dr. Elkind. “It is likely that the cumulative effect of blood pressure over time has a big role to play — and it does seem clear that midlife blood pressure is even more important than blood pressure late in life.”

That said, he added, “In general and all things being equal, I would treat to a blood pressure of < 120/80 mmHg,” given the SPRINT trial findings of greater benefits when treating to this systolic blood pressure goal. “Of course, if patients have side effects such as lightheadedness or dizziness or other medical conditions that require a higher target, then one would need to adjust the treatment targets.”

According to Dr. Fuster, targets should not be the focus because they vary. For example, the ACC/AHA guidelines use < 130/80 mm Hg, whereas the European Society of Hypertension guidelines and those of the American Academy of Family Physicians specify < 140/90 mm Hg and include age-based criteria. Because there are no studies comparing the outcomes of one set of guidelines vs another, Dr. Fuster thinks the focus should be on starting treatment as early as possible to prevent hypertension leading to dementia.

He pointed to the ongoing PESA trial, which uses brain MRI and other tests to characterize longitudinal associations among cerebral glucose metabolism, subclinical atherosclerosis, and cardiovascular risk factors in asymptomatic individuals aged 40-54. Most did not have hypertension at baseline.

A recently published analysis of a subcohort of 370 PESA participants found that those with persistent high cardiovascular risk and subclinical carotid atherosclerosis already had signs of brain metabolic decline, “suggesting that maintenance of cardiovascular health during midlife could contribute to reductions in neurodegenerative disease burden later in life,” wrote the investigators.
 

Is It Ever Too Late?

If starting hypertension treatment in midlife can help reduce the risk for cognitive impairment later, can treating later in life also help? “It’s theoretically possible, but it has to be proven,” Dr. Fuster said. “There are no data on whether there’s less chance to prevent the development of dementia if you start treating hypertension at age 70, for example. And we have no idea whether hypertension treatment will prevent progression in those who already have dementia.”

“Treating high blood pressure in older adults could affect the course of further progressive cognitive decline by improving vascular health and preventing strokes, which likely exacerbate nonvascular dementia,” Dr. Elkind suggested. “Most people with dementia have a combination of vascular and nonvascular dementia, so treating reversible causes wherever possible makes a difference.”

Dr. Elkind treats older patients with this in mind, he said, “even though most of the evidence points to the fact that it is blood pressure in middle age, not older age, that seems to have the biggest impact on later-life cognitive decline and dementia.” Like Dr. Fuster, he said, “the best strategy is to identify and treat blood pressure in midlife, before damage to the brain has advanced.”

Dr. Moran noted, “The latest science on dementia causes suggests it is difficult to draw a border between vascular and nonvascular dementia. So, as a practical matter, healthcare providers should consider that hypertension treatment is one of the best ways to prevent any category of dementia. This dementia prevention is added to the well-known benefits of hypertension treatment to prevent heart attacks, strokes, and kidney disease: ‘Healthy heart, healthy brain.’ ”

“Our BP [blood pressure] control rates overall are still abysmal,” Dr. Handberg added. Currently around one in four US adults with hypertension have it under control. Studies have shown that blood pressure control rates of 70%-80% are achievable, she said. “We can’t let patient or provider inertia continue.”

Dr. Handberg, Dr. Elkind, Dr. Moran, and Dr. Fuster declared no relevant conflicts of interest.

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

High blood pressure is an established risk factor for neurodegeneration and cognitive decline. Long-standing evidence shows that treating hypertension can reduce its vascular consequences, but whether that is true for neurodegeneration is less clear.

Valentin Fuster, MD, president of Mount Sinai Fuster Heart Hospital in New York City, told this news organization. “There is no question in the literature that untreated high blood pressure may lead to dementia,” he said. “The open question is whether treating blood pressure is sufficient to decrease or stop the progress of dementia.”

Studies are mixed, but recent research suggests that addressing hypertension does affect the risk for dementia. A secondary analysis of the China Rural Hypertension Control Project reported at the American Heart Association (AHA) Scientific Sessions in 2023 but not yet published showed that the 4-year blood pressure–lowering program in adults aged 40 or older significantly reduced the risk for all-cause dementia and cognitive impairment.

Similarly, a post hoc analysis of the SPRINT MIND trial found that participants aged 50 or older who underwent intensive (< 120 mm Hg) vs standard (< 140 mm Hg) blood pressure lowering had a lower rate of probable dementia or mild cognitive impairment.

Other studies pointing to a benefit included a pooled individual participant analysis of five randomized controlled trials, which found class I evidence to support antihypertensive treatment to reduce the risk for incident dementia, and an earlier systematic review and meta-analysis of the association of blood pressure lowering with newly diagnosed dementia or cognitive impairment.
 

How It Might Work

Some possible mechanisms underlying the connection have emerged.

“Vascular disease caused by hypertension is clearly implicated in one form of dementia, called vascular cognitive impairment and dementia,” Andrew Moran, MD, PhD, associate professor of medicine at Columbia University Vagelos College of Physicians and Surgeons in New York City, told this news organization. “This category includes dementia following a stroke caused by uncontrolled hypertension.” 

“At the same time, we now know that hypertension and other vascular risk factors can also contribute, along with other factors, to developing Alzheimer dementia,” he said. “Even without causing clinically evident stroke, vascular disease from hypertension can lead to subtle damage to the brain via ischemia, microhemorrhage, and atrophy.”

“It is well known that hypertension affects the vasculature, and the vasculature of the brain is not spared,” agreed Eileen Handberg, PhD, ARNP, a member of the Hypertension Workgroup at the American College of Cardiology (ACC) and a professor of medicine and director of the Cardiovascular Clinical Trials Program in the University of Florida, Gainesville, Florida. “Combine this with other mechanisms like inflammation and endothelial dysfunction, and add amyloid accumulation, and there is a deterioration in vascular beds leading to decreased cerebral blood flow,” she said.

Treating hypertension likely helps lower dementia risk through “a combination of reduced risk of stroke and also benefits on blood flow, blood vessel health, and reduction in neurodegeneration,” suggested Mitchell S.V. Elkind, MD, chief clinical science officer and past president of the AHA and a professor of neurology and epidemiology at Columbia University Irving Medical Center in New York City. “Midlife blood pressure elevations are associated with deposition of amyloid in the brain, so controlling blood pressure may reduce amyloid deposits and neurodegeneration.”
 

Time in Range or Treat to Target?

With respect to dementia risk, does treating hypertension to a specific target make a difference, or is it the time spent in a healthy blood pressure range? 

“Observational studies and a post hoc analysis of the SPRINT MIND trial suggest that more time spent in a healthy blood pressure range or more stable blood pressure are associated with lower dementia risk,” Dr. Moran said. Citing results of the CHRC program and SPRINT MIND trial, he suggested that while a dose-response effect (the lower the blood pressure, the lower the dementia risk) hasn’t been definitively demonstrated, it is likely the case.

In his practice, Dr. Moran follows ACC/AHA guidelines and prescribes antihypertensives to get blood pressure below 130/80 mm Hg in individuals with hypertension who have other high-risk factors (cardiovascular disease, diabetes, chronic kidney disease, or high risk for these conditions). “The treatment rule for people with hypertension without these other risk factors is less clear — lowering blood pressure below 140/90 mm Hg is a must; I will discuss with patients whether to go lower than that.”

“The relative contributions of time in range versus treating to a target for blood pressure require further study,” said Dr. Elkind. “It is likely that the cumulative effect of blood pressure over time has a big role to play — and it does seem clear that midlife blood pressure is even more important than blood pressure late in life.”

That said, he added, “In general and all things being equal, I would treat to a blood pressure of < 120/80 mmHg,” given the SPRINT trial findings of greater benefits when treating to this systolic blood pressure goal. “Of course, if patients have side effects such as lightheadedness or dizziness or other medical conditions that require a higher target, then one would need to adjust the treatment targets.”

According to Dr. Fuster, targets should not be the focus because they vary. For example, the ACC/AHA guidelines use < 130/80 mm Hg, whereas the European Society of Hypertension guidelines and those of the American Academy of Family Physicians specify < 140/90 mm Hg and include age-based criteria. Because there are no studies comparing the outcomes of one set of guidelines vs another, Dr. Fuster thinks the focus should be on starting treatment as early as possible to prevent hypertension leading to dementia.

He pointed to the ongoing PESA trial, which uses brain MRI and other tests to characterize longitudinal associations among cerebral glucose metabolism, subclinical atherosclerosis, and cardiovascular risk factors in asymptomatic individuals aged 40-54. Most did not have hypertension at baseline.

A recently published analysis of a subcohort of 370 PESA participants found that those with persistent high cardiovascular risk and subclinical carotid atherosclerosis already had signs of brain metabolic decline, “suggesting that maintenance of cardiovascular health during midlife could contribute to reductions in neurodegenerative disease burden later in life,” wrote the investigators.
 

Is It Ever Too Late?

If starting hypertension treatment in midlife can help reduce the risk for cognitive impairment later, can treating later in life also help? “It’s theoretically possible, but it has to be proven,” Dr. Fuster said. “There are no data on whether there’s less chance to prevent the development of dementia if you start treating hypertension at age 70, for example. And we have no idea whether hypertension treatment will prevent progression in those who already have dementia.”

“Treating high blood pressure in older adults could affect the course of further progressive cognitive decline by improving vascular health and preventing strokes, which likely exacerbate nonvascular dementia,” Dr. Elkind suggested. “Most people with dementia have a combination of vascular and nonvascular dementia, so treating reversible causes wherever possible makes a difference.”

Dr. Elkind treats older patients with this in mind, he said, “even though most of the evidence points to the fact that it is blood pressure in middle age, not older age, that seems to have the biggest impact on later-life cognitive decline and dementia.” Like Dr. Fuster, he said, “the best strategy is to identify and treat blood pressure in midlife, before damage to the brain has advanced.”

Dr. Moran noted, “The latest science on dementia causes suggests it is difficult to draw a border between vascular and nonvascular dementia. So, as a practical matter, healthcare providers should consider that hypertension treatment is one of the best ways to prevent any category of dementia. This dementia prevention is added to the well-known benefits of hypertension treatment to prevent heart attacks, strokes, and kidney disease: ‘Healthy heart, healthy brain.’ ”

“Our BP [blood pressure] control rates overall are still abysmal,” Dr. Handberg added. Currently around one in four US adults with hypertension have it under control. Studies have shown that blood pressure control rates of 70%-80% are achievable, she said. “We can’t let patient or provider inertia continue.”

Dr. Handberg, Dr. Elkind, Dr. Moran, and Dr. Fuster declared no relevant conflicts of interest.

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

High blood pressure is an established risk factor for neurodegeneration and cognitive decline. Long-standing evidence shows that treating hypertension can reduce its vascular consequences, but whether that is true for neurodegeneration is less clear.

Valentin Fuster, MD, president of Mount Sinai Fuster Heart Hospital in New York City, told this news organization. “There is no question in the literature that untreated high blood pressure may lead to dementia,” he said. “The open question is whether treating blood pressure is sufficient to decrease or stop the progress of dementia.”

Studies are mixed, but recent research suggests that addressing hypertension does affect the risk for dementia. A secondary analysis of the China Rural Hypertension Control Project reported at the American Heart Association (AHA) Scientific Sessions in 2023 but not yet published showed that the 4-year blood pressure–lowering program in adults aged 40 or older significantly reduced the risk for all-cause dementia and cognitive impairment.

Similarly, a post hoc analysis of the SPRINT MIND trial found that participants aged 50 or older who underwent intensive (< 120 mm Hg) vs standard (< 140 mm Hg) blood pressure lowering had a lower rate of probable dementia or mild cognitive impairment.

Other studies pointing to a benefit included a pooled individual participant analysis of five randomized controlled trials, which found class I evidence to support antihypertensive treatment to reduce the risk for incident dementia, and an earlier systematic review and meta-analysis of the association of blood pressure lowering with newly diagnosed dementia or cognitive impairment.
 

How It Might Work

Some possible mechanisms underlying the connection have emerged.

“Vascular disease caused by hypertension is clearly implicated in one form of dementia, called vascular cognitive impairment and dementia,” Andrew Moran, MD, PhD, associate professor of medicine at Columbia University Vagelos College of Physicians and Surgeons in New York City, told this news organization. “This category includes dementia following a stroke caused by uncontrolled hypertension.” 

“At the same time, we now know that hypertension and other vascular risk factors can also contribute, along with other factors, to developing Alzheimer dementia,” he said. “Even without causing clinically evident stroke, vascular disease from hypertension can lead to subtle damage to the brain via ischemia, microhemorrhage, and atrophy.”

“It is well known that hypertension affects the vasculature, and the vasculature of the brain is not spared,” agreed Eileen Handberg, PhD, ARNP, a member of the Hypertension Workgroup at the American College of Cardiology (ACC) and a professor of medicine and director of the Cardiovascular Clinical Trials Program in the University of Florida, Gainesville, Florida. “Combine this with other mechanisms like inflammation and endothelial dysfunction, and add amyloid accumulation, and there is a deterioration in vascular beds leading to decreased cerebral blood flow,” she said.

Treating hypertension likely helps lower dementia risk through “a combination of reduced risk of stroke and also benefits on blood flow, blood vessel health, and reduction in neurodegeneration,” suggested Mitchell S.V. Elkind, MD, chief clinical science officer and past president of the AHA and a professor of neurology and epidemiology at Columbia University Irving Medical Center in New York City. “Midlife blood pressure elevations are associated with deposition of amyloid in the brain, so controlling blood pressure may reduce amyloid deposits and neurodegeneration.”
 

Time in Range or Treat to Target?

With respect to dementia risk, does treating hypertension to a specific target make a difference, or is it the time spent in a healthy blood pressure range? 

“Observational studies and a post hoc analysis of the SPRINT MIND trial suggest that more time spent in a healthy blood pressure range or more stable blood pressure are associated with lower dementia risk,” Dr. Moran said. Citing results of the CHRC program and SPRINT MIND trial, he suggested that while a dose-response effect (the lower the blood pressure, the lower the dementia risk) hasn’t been definitively demonstrated, it is likely the case.

In his practice, Dr. Moran follows ACC/AHA guidelines and prescribes antihypertensives to get blood pressure below 130/80 mm Hg in individuals with hypertension who have other high-risk factors (cardiovascular disease, diabetes, chronic kidney disease, or high risk for these conditions). “The treatment rule for people with hypertension without these other risk factors is less clear — lowering blood pressure below 140/90 mm Hg is a must; I will discuss with patients whether to go lower than that.”

“The relative contributions of time in range versus treating to a target for blood pressure require further study,” said Dr. Elkind. “It is likely that the cumulative effect of blood pressure over time has a big role to play — and it does seem clear that midlife blood pressure is even more important than blood pressure late in life.”

That said, he added, “In general and all things being equal, I would treat to a blood pressure of < 120/80 mmHg,” given the SPRINT trial findings of greater benefits when treating to this systolic blood pressure goal. “Of course, if patients have side effects such as lightheadedness or dizziness or other medical conditions that require a higher target, then one would need to adjust the treatment targets.”

According to Dr. Fuster, targets should not be the focus because they vary. For example, the ACC/AHA guidelines use < 130/80 mm Hg, whereas the European Society of Hypertension guidelines and those of the American Academy of Family Physicians specify < 140/90 mm Hg and include age-based criteria. Because there are no studies comparing the outcomes of one set of guidelines vs another, Dr. Fuster thinks the focus should be on starting treatment as early as possible to prevent hypertension leading to dementia.

He pointed to the ongoing PESA trial, which uses brain MRI and other tests to characterize longitudinal associations among cerebral glucose metabolism, subclinical atherosclerosis, and cardiovascular risk factors in asymptomatic individuals aged 40-54. Most did not have hypertension at baseline.

A recently published analysis of a subcohort of 370 PESA participants found that those with persistent high cardiovascular risk and subclinical carotid atherosclerosis already had signs of brain metabolic decline, “suggesting that maintenance of cardiovascular health during midlife could contribute to reductions in neurodegenerative disease burden later in life,” wrote the investigators.
 

Is It Ever Too Late?

If starting hypertension treatment in midlife can help reduce the risk for cognitive impairment later, can treating later in life also help? “It’s theoretically possible, but it has to be proven,” Dr. Fuster said. “There are no data on whether there’s less chance to prevent the development of dementia if you start treating hypertension at age 70, for example. And we have no idea whether hypertension treatment will prevent progression in those who already have dementia.”

“Treating high blood pressure in older adults could affect the course of further progressive cognitive decline by improving vascular health and preventing strokes, which likely exacerbate nonvascular dementia,” Dr. Elkind suggested. “Most people with dementia have a combination of vascular and nonvascular dementia, so treating reversible causes wherever possible makes a difference.”

Dr. Elkind treats older patients with this in mind, he said, “even though most of the evidence points to the fact that it is blood pressure in middle age, not older age, that seems to have the biggest impact on later-life cognitive decline and dementia.” Like Dr. Fuster, he said, “the best strategy is to identify and treat blood pressure in midlife, before damage to the brain has advanced.”

Dr. Moran noted, “The latest science on dementia causes suggests it is difficult to draw a border between vascular and nonvascular dementia. So, as a practical matter, healthcare providers should consider that hypertension treatment is one of the best ways to prevent any category of dementia. This dementia prevention is added to the well-known benefits of hypertension treatment to prevent heart attacks, strokes, and kidney disease: ‘Healthy heart, healthy brain.’ ”

“Our BP [blood pressure] control rates overall are still abysmal,” Dr. Handberg added. Currently around one in four US adults with hypertension have it under control. Studies have shown that blood pressure control rates of 70%-80% are achievable, she said. “We can’t let patient or provider inertia continue.”

Dr. Handberg, Dr. Elkind, Dr. Moran, and Dr. Fuster declared no relevant conflicts of interest.

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

Within the next few years, patients will go to their primary care facility for a medical problem. They’ll be greeted by a nonhuman who speaks in the language of their choice. Based upon the initial interview, which will be taken in note form, the patient will be diagnosed, and a prescription called into the pharmacy. They’ll pay the robot at a reception kiosk, and their meds will be delivered via driverless car.

Or so suggests Allan Stewart, MD, medical director and chief of cardiothoracic surgery at HCA Florida Mercy Hospital in Miami.

The writing is on the wall. Artificial intelligence (AI) is only going to play a more significant role in healthcare, and the entire patient experience will be much different in the next 5 years, he said.

If that sounds far too futuristic, buckle up. AI is already here and being used by most medical specialties. However, it’s primary care that stands to gain the most from this technology — right now — thanks to its ability to radically streamline patient care.
 

Seeing the Doctor and His or Her AI Assistant

AI is making doctors’ work lives easier, whether the technology helps with risk prevention and intervention or closing care gaps. It can also triage patient complaints, monitor patients remotely, or even perform digital health coaching to keep patients on track with their lifestyle regimens or monitor their health conditions.

Each of these AI components enables primary care physicians to reduce some of the paperwork requirements of their jobs and do what they were trained to do — listen and assess patients. Doctors currently spend 12 hours on average each week submitting prior authorization requests, according to an American Medical Association survey.

“Primary care can be overwhelming, especially today, with the advent of electronic records and data,” said Davin Lundquist, MD, a family medicine physician and chief medical officer at Augmedix, an automated medical documentation company that provides tools to reduce clinician burnout. “The amount of data we have to go through to try to get a complete and clear picture of our patients can be overwhelming on top of the referrals, administrative burdens, and regulatory requirements, which seem to be focused on the primary care space,” Dr. Lundquist said.

With an AI assist, primary care physicians can reduce their prep and pre-charting time, lessen the time needed for paperwork outside of clinic hours, and streamline information, including access to lab results, radiology reports, and consults.

“AI is already helping doctors manage their practices, make differential diagnoses, and input progress notes or histories,” said Dr. Stewart.

In Seattle, Ford Parsons, MD, chief of operational analytics at Providence Hospitals in Seattle, has been leading a generative AI project that recently developed a tool called Provaria to prioritize incoming messages from patients. The tool ensures that those with more urgent needs get immediate attention, and it supports the personnel who lead the responses.

The process begins with Provaria reviewing patient messages to ensure those with more urgent needs, such as a mental health crisis, get immediate attention instead of answering messages in the order they were received.

Provaria also provides resources to help responding staff craft a reply. If a patient’s message cites back pain, for example, the system might suggest a referral to a physical therapist, include a link to that department, and prompt the staff to ask about red flags that indicate a more urgent situation.

After an initial rollout, Providence recently deployed Provaria to manage the messages for all 4000 of its primary care, family medicine, and internal medicine providers. The system has reviewed and categorized more than 500,000 messages so far.

“This is another example where AI can increase the human connection in healthcare,” Dr. Parsons said. “That’s the opposite of what others are saying, but by using AI, you can automate the stuff that isn’t critical that doctors have wound up doing.”
 

AI Helps Foster Better Person-to-Person Communication

In recent years, the first thing most doctors do when they enter the exam room with a patient is log into the in-room computer and start to take notes — which can be off-putting to patients.

Now devices can ease this process, such as PLAUD, an AI voice recognition device that attaches to a cell phone. Just the size of a credit card, the device enables conversations to be easily recorded. It not only streamlines note-taking but also enables a physician to listen intently to a patient’s concerns instead of furiously jotting down notes.

“That device is already helping transcribe conversations into notes and then into a patient’s electronic medical record,” Dr. Stewart said. “This helps save doctors the work of having to input patient information.”
 

AI Can’t Be a Compassionate Human

The one thing AI can’t do is show compassion, at least not yet. The someday “vision” when a robot will gather intel about a patient’s symptoms and even offer a diagnosis does have some downsides. There is no replacement for human interaction, especially in the case of dire health news.

“If you have signs of a metastatic cancer and a nonhuman is delivering this news, there’s no way AI can share this news with compassion,” said Dr. Stewart.

For now, AI is becoming instrumental in helping reduce the number of extra demands on primary care doctors, as well as physicians in other specialties, so that they can continue focusing on what matters — healing patients.
 

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

Within the next few years, patients will go to their primary care facility for a medical problem. They’ll be greeted by a nonhuman who speaks in the language of their choice. Based upon the initial interview, which will be taken in note form, the patient will be diagnosed, and a prescription called into the pharmacy. They’ll pay the robot at a reception kiosk, and their meds will be delivered via driverless car.

Or so suggests Allan Stewart, MD, medical director and chief of cardiothoracic surgery at HCA Florida Mercy Hospital in Miami.

The writing is on the wall. Artificial intelligence (AI) is only going to play a more significant role in healthcare, and the entire patient experience will be much different in the next 5 years, he said.

If that sounds far too futuristic, buckle up. AI is already here and being used by most medical specialties. However, it’s primary care that stands to gain the most from this technology — right now — thanks to its ability to radically streamline patient care.
 

Seeing the Doctor and His or Her AI Assistant

AI is making doctors’ work lives easier, whether the technology helps with risk prevention and intervention or closing care gaps. It can also triage patient complaints, monitor patients remotely, or even perform digital health coaching to keep patients on track with their lifestyle regimens or monitor their health conditions.

Each of these AI components enables primary care physicians to reduce some of the paperwork requirements of their jobs and do what they were trained to do — listen and assess patients. Doctors currently spend 12 hours on average each week submitting prior authorization requests, according to an American Medical Association survey.

“Primary care can be overwhelming, especially today, with the advent of electronic records and data,” said Davin Lundquist, MD, a family medicine physician and chief medical officer at Augmedix, an automated medical documentation company that provides tools to reduce clinician burnout. “The amount of data we have to go through to try to get a complete and clear picture of our patients can be overwhelming on top of the referrals, administrative burdens, and regulatory requirements, which seem to be focused on the primary care space,” Dr. Lundquist said.

With an AI assist, primary care physicians can reduce their prep and pre-charting time, lessen the time needed for paperwork outside of clinic hours, and streamline information, including access to lab results, radiology reports, and consults.

“AI is already helping doctors manage their practices, make differential diagnoses, and input progress notes or histories,” said Dr. Stewart.

In Seattle, Ford Parsons, MD, chief of operational analytics at Providence Hospitals in Seattle, has been leading a generative AI project that recently developed a tool called Provaria to prioritize incoming messages from patients. The tool ensures that those with more urgent needs get immediate attention, and it supports the personnel who lead the responses.

The process begins with Provaria reviewing patient messages to ensure those with more urgent needs, such as a mental health crisis, get immediate attention instead of answering messages in the order they were received.

Provaria also provides resources to help responding staff craft a reply. If a patient’s message cites back pain, for example, the system might suggest a referral to a physical therapist, include a link to that department, and prompt the staff to ask about red flags that indicate a more urgent situation.

After an initial rollout, Providence recently deployed Provaria to manage the messages for all 4000 of its primary care, family medicine, and internal medicine providers. The system has reviewed and categorized more than 500,000 messages so far.

“This is another example where AI can increase the human connection in healthcare,” Dr. Parsons said. “That’s the opposite of what others are saying, but by using AI, you can automate the stuff that isn’t critical that doctors have wound up doing.”
 

AI Helps Foster Better Person-to-Person Communication

In recent years, the first thing most doctors do when they enter the exam room with a patient is log into the in-room computer and start to take notes — which can be off-putting to patients.

Now devices can ease this process, such as PLAUD, an AI voice recognition device that attaches to a cell phone. Just the size of a credit card, the device enables conversations to be easily recorded. It not only streamlines note-taking but also enables a physician to listen intently to a patient’s concerns instead of furiously jotting down notes.

“That device is already helping transcribe conversations into notes and then into a patient’s electronic medical record,” Dr. Stewart said. “This helps save doctors the work of having to input patient information.”
 

AI Can’t Be a Compassionate Human

The one thing AI can’t do is show compassion, at least not yet. The someday “vision” when a robot will gather intel about a patient’s symptoms and even offer a diagnosis does have some downsides. There is no replacement for human interaction, especially in the case of dire health news.

“If you have signs of a metastatic cancer and a nonhuman is delivering this news, there’s no way AI can share this news with compassion,” said Dr. Stewart.

For now, AI is becoming instrumental in helping reduce the number of extra demands on primary care doctors, as well as physicians in other specialties, so that they can continue focusing on what matters — healing patients.
 

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

Within the next few years, patients will go to their primary care facility for a medical problem. They’ll be greeted by a nonhuman who speaks in the language of their choice. Based upon the initial interview, which will be taken in note form, the patient will be diagnosed, and a prescription called into the pharmacy. They’ll pay the robot at a reception kiosk, and their meds will be delivered via driverless car.

Or so suggests Allan Stewart, MD, medical director and chief of cardiothoracic surgery at HCA Florida Mercy Hospital in Miami.

The writing is on the wall. Artificial intelligence (AI) is only going to play a more significant role in healthcare, and the entire patient experience will be much different in the next 5 years, he said.

If that sounds far too futuristic, buckle up. AI is already here and being used by most medical specialties. However, it’s primary care that stands to gain the most from this technology — right now — thanks to its ability to radically streamline patient care.
 

Seeing the Doctor and His or Her AI Assistant

AI is making doctors’ work lives easier, whether the technology helps with risk prevention and intervention or closing care gaps. It can also triage patient complaints, monitor patients remotely, or even perform digital health coaching to keep patients on track with their lifestyle regimens or monitor their health conditions.

Each of these AI components enables primary care physicians to reduce some of the paperwork requirements of their jobs and do what they were trained to do — listen and assess patients. Doctors currently spend 12 hours on average each week submitting prior authorization requests, according to an American Medical Association survey.

“Primary care can be overwhelming, especially today, with the advent of electronic records and data,” said Davin Lundquist, MD, a family medicine physician and chief medical officer at Augmedix, an automated medical documentation company that provides tools to reduce clinician burnout. “The amount of data we have to go through to try to get a complete and clear picture of our patients can be overwhelming on top of the referrals, administrative burdens, and regulatory requirements, which seem to be focused on the primary care space,” Dr. Lundquist said.

With an AI assist, primary care physicians can reduce their prep and pre-charting time, lessen the time needed for paperwork outside of clinic hours, and streamline information, including access to lab results, radiology reports, and consults.

“AI is already helping doctors manage their practices, make differential diagnoses, and input progress notes or histories,” said Dr. Stewart.

In Seattle, Ford Parsons, MD, chief of operational analytics at Providence Hospitals in Seattle, has been leading a generative AI project that recently developed a tool called Provaria to prioritize incoming messages from patients. The tool ensures that those with more urgent needs get immediate attention, and it supports the personnel who lead the responses.

The process begins with Provaria reviewing patient messages to ensure those with more urgent needs, such as a mental health crisis, get immediate attention instead of answering messages in the order they were received.

Provaria also provides resources to help responding staff craft a reply. If a patient’s message cites back pain, for example, the system might suggest a referral to a physical therapist, include a link to that department, and prompt the staff to ask about red flags that indicate a more urgent situation.

After an initial rollout, Providence recently deployed Provaria to manage the messages for all 4000 of its primary care, family medicine, and internal medicine providers. The system has reviewed and categorized more than 500,000 messages so far.

“This is another example where AI can increase the human connection in healthcare,” Dr. Parsons said. “That’s the opposite of what others are saying, but by using AI, you can automate the stuff that isn’t critical that doctors have wound up doing.”
 

AI Helps Foster Better Person-to-Person Communication

In recent years, the first thing most doctors do when they enter the exam room with a patient is log into the in-room computer and start to take notes — which can be off-putting to patients.

Now devices can ease this process, such as PLAUD, an AI voice recognition device that attaches to a cell phone. Just the size of a credit card, the device enables conversations to be easily recorded. It not only streamlines note-taking but also enables a physician to listen intently to a patient’s concerns instead of furiously jotting down notes.

“That device is already helping transcribe conversations into notes and then into a patient’s electronic medical record,” Dr. Stewart said. “This helps save doctors the work of having to input patient information.”
 

AI Can’t Be a Compassionate Human

The one thing AI can’t do is show compassion, at least not yet. The someday “vision” when a robot will gather intel about a patient’s symptoms and even offer a diagnosis does have some downsides. There is no replacement for human interaction, especially in the case of dire health news.

“If you have signs of a metastatic cancer and a nonhuman is delivering this news, there’s no way AI can share this news with compassion,” said Dr. Stewart.

For now, AI is becoming instrumental in helping reduce the number of extra demands on primary care doctors, as well as physicians in other specialties, so that they can continue focusing on what matters — healing patients.
 

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

In this article, I will review several recently published articles and guidelines relevant to the care of older adults in primary care. The articles of interest address statins for primary prevention, vitamin D supplementation and testing, and physical activity for healthy aging.
 

Statins for Primary Prevention of Cardiovascular Disease

A common conundrum in primary care is whether an older adult should be on a statin for primary prevention. This question has been difficult to answer because of the underrepresentation of older adults in clinical trials that examine the effect of statins for primary prevention. A recent study by Xu et al. published in Annals of Internal Medicine sought to address this gap in knowledge, investigating the risks and benefits of statins for primary prevention for older adults.¹

This study stratified participants by “old” (aged 75-84 years) and “very old” (85 years or older). In this study, older adults who had an indication for statins were initiated on statins and studied over a 5-year period and compared with age-matched cohorts not initiated on statin therapy. Participants with known cardiovascular disease at baseline were excluded. The outcomes of interest were major cardiovascular disease (CVD) (a composite of myocardial infarction, stroke, or heart failure), all-cause mortality, and adverse effect of drug therapy (myopathy or liver dysfunction).

The study found that among older adults aged 75-84, initiation of statin therapy led to a 1.2% risk reduction in major CVD over a 5-year period. For older adults aged 85 and greater, initiation of statins had an even larger impact, leading to a 4.4% risk reduction in major CVD over a 5-year period. The study found that there was no significant difference in adverse effects including myopathy or liver dysfunction in both age groups.

Statins, the study suggests, are appropriate and safe to initiate for primary prevention in older adults and can lead to substantial benefits in reduction of CVD. While time to benefit was not explicitly examined in this study, a prior study by Yourman et al. suggested that the time to benefit for statins for primary prevention in adults aged 50-75 would be least 2.5 years.²

My takeaway from these findings is to discuss statin initiation for primary prevention for older patients who are focused on longevity, have good functional status (often used in geriatrics as a proxy for prognosis), and are willing to accept more medications.
 

Empiric Vitamin D Supplementation in Adults over 75 Years

Vitamin D is one of the most common supplements taken by older adults but evidence supporting vitamin D supplementation is variable in published literature, as most data comes from observational trials. New guidelines from the Endocrine Society focused on developing recommendations for healthy individuals with data obtained from randomized controlled trials (RCTs) and large longitudinal observational trials with comparison groups if RCTs were not available. These guidelines recommend against empiric supplementation of vitamin D for healthy adults aged 18-74, excluding pregnant women and patients with high-risk diabetes.³

For older adults aged 75 or greater, empiric vitamin D supplementation is recommended because of the possible reduction of risk in all-cause mortality in this population. Of note, this was a grade 2 recommendation by the panel, indicating that the benefits of the treatment probably outweigh the risks. The panel stated that vitamin D supplementation could be delivered through fortified foods, multivitamins with vitamin D, or as a separate vitamin D supplement.

The dosage should remain within the recommended daily allowance outlined by the Institute of Medicine of 800 IU daily for adults over 70, and the panel recommends low-dose daily vitamin D supplementation over high-dose interval supplementation. The panel noted that routine screening of vitamin D levels should not be used to guide decision-making on whether to start supplementation, but vitamin D levels should be obtained for patients who have an indication for evaluation.

The reviewers highlight that these guidelines were developed for healthy individuals and are not applicable to those with conditions that warrant vitamin D evaluation. In my clinical practice, many of my patients have bone-mineral conditions and cognitive impairment that warrant evaluation. Based on these guidelines, I will consider empiric vitamin D supplementation more often for healthy patients aged 75 and older.
 

Sedentary Behaviors and Healthy Aging

Engaging inactive older adults in regular physical activity can be challenging, particularly as the pandemic has led to more pervasive social isolation and affected the availability of in-person exercise activities in the community. Physical activity is a key component of healthy aging and cognition, and its benefits should be a part of routine counseling for older adults.

An interesting recent study published in JAMA Network Open by Shi et al. evaluated the association of health behaviors and aging in female US nurses over a 20-year period.⁴ Surveys were administered to capture time spent in each behavior, such as being sedentary (TV watching, sitting at home or at work), light activity (walking around the house or at work), and moderate to vigorous activity (walking for exercise, lawn mowing). “Healthy aging” was defined by the absence of chronic conditions such as heart failure, and lack of physical, mental, and cognitive impairment.

The study found that participants who were more sedentary were less likely to age healthfully, with each additional 2 hours of TV watching per day associated with a 12% reduction in likelihood of healthy aging. Light physical activity was associated with a significant increase in healthy aging, with a 6% increase in the likelihood of healthy aging for each additional 2 hours of light activity. Each additional 1 hour of moderate to vigorous activity was associated with a 14% increase in the likelihood of healthy aging. These findings support discussions with patients that behavior change, even in small increments, can be beneficial in healthy aging.
 

References

1. Xu W et al. Ann Intern Med. 2024 Jun;177(6):701-10.

2. Yourman LC et al. JAMA Intern Med. 2021;181:179-85.

3. Demay MB et al. J Clin Endocrinol Metab. August 2024;109(8):1907-47.

4. Shi H et al. JAMA Netw Open. 2024;7(6):e2416300.

In this article, I will review several recently published articles and guidelines relevant to the care of older adults in primary care. The articles of interest address statins for primary prevention, vitamin D supplementation and testing, and physical activity for healthy aging.
 

Statins for Primary Prevention of Cardiovascular Disease

A common conundrum in primary care is whether an older adult should be on a statin for primary prevention. This question has been difficult to answer because of the underrepresentation of older adults in clinical trials that examine the effect of statins for primary prevention. A recent study by Xu et al. published in Annals of Internal Medicine sought to address this gap in knowledge, investigating the risks and benefits of statins for primary prevention for older adults.¹

This study stratified participants by “old” (aged 75-84 years) and “very old” (85 years or older). In this study, older adults who had an indication for statins were initiated on statins and studied over a 5-year period and compared with age-matched cohorts not initiated on statin therapy. Participants with known cardiovascular disease at baseline were excluded. The outcomes of interest were major cardiovascular disease (CVD) (a composite of myocardial infarction, stroke, or heart failure), all-cause mortality, and adverse effect of drug therapy (myopathy or liver dysfunction).

The study found that among older adults aged 75-84, initiation of statin therapy led to a 1.2% risk reduction in major CVD over a 5-year period. For older adults aged 85 and greater, initiation of statins had an even larger impact, leading to a 4.4% risk reduction in major CVD over a 5-year period. The study found that there was no significant difference in adverse effects including myopathy or liver dysfunction in both age groups.

Statins, the study suggests, are appropriate and safe to initiate for primary prevention in older adults and can lead to substantial benefits in reduction of CVD. While time to benefit was not explicitly examined in this study, a prior study by Yourman et al. suggested that the time to benefit for statins for primary prevention in adults aged 50-75 would be least 2.5 years.²

My takeaway from these findings is to discuss statin initiation for primary prevention for older patients who are focused on longevity, have good functional status (often used in geriatrics as a proxy for prognosis), and are willing to accept more medications.
 

Empiric Vitamin D Supplementation in Adults over 75 Years

Vitamin D is one of the most common supplements taken by older adults but evidence supporting vitamin D supplementation is variable in published literature, as most data comes from observational trials. New guidelines from the Endocrine Society focused on developing recommendations for healthy individuals with data obtained from randomized controlled trials (RCTs) and large longitudinal observational trials with comparison groups if RCTs were not available. These guidelines recommend against empiric supplementation of vitamin D for healthy adults aged 18-74, excluding pregnant women and patients with high-risk diabetes.³

For older adults aged 75 or greater, empiric vitamin D supplementation is recommended because of the possible reduction of risk in all-cause mortality in this population. Of note, this was a grade 2 recommendation by the panel, indicating that the benefits of the treatment probably outweigh the risks. The panel stated that vitamin D supplementation could be delivered through fortified foods, multivitamins with vitamin D, or as a separate vitamin D supplement.

The dosage should remain within the recommended daily allowance outlined by the Institute of Medicine of 800 IU daily for adults over 70, and the panel recommends low-dose daily vitamin D supplementation over high-dose interval supplementation. The panel noted that routine screening of vitamin D levels should not be used to guide decision-making on whether to start supplementation, but vitamin D levels should be obtained for patients who have an indication for evaluation.

The reviewers highlight that these guidelines were developed for healthy individuals and are not applicable to those with conditions that warrant vitamin D evaluation. In my clinical practice, many of my patients have bone-mineral conditions and cognitive impairment that warrant evaluation. Based on these guidelines, I will consider empiric vitamin D supplementation more often for healthy patients aged 75 and older.
 

Sedentary Behaviors and Healthy Aging

Engaging inactive older adults in regular physical activity can be challenging, particularly as the pandemic has led to more pervasive social isolation and affected the availability of in-person exercise activities in the community. Physical activity is a key component of healthy aging and cognition, and its benefits should be a part of routine counseling for older adults.

An interesting recent study published in JAMA Network Open by Shi et al. evaluated the association of health behaviors and aging in female US nurses over a 20-year period.⁴ Surveys were administered to capture time spent in each behavior, such as being sedentary (TV watching, sitting at home or at work), light activity (walking around the house or at work), and moderate to vigorous activity (walking for exercise, lawn mowing). “Healthy aging” was defined by the absence of chronic conditions such as heart failure, and lack of physical, mental, and cognitive impairment.

The study found that participants who were more sedentary were less likely to age healthfully, with each additional 2 hours of TV watching per day associated with a 12% reduction in likelihood of healthy aging. Light physical activity was associated with a significant increase in healthy aging, with a 6% increase in the likelihood of healthy aging for each additional 2 hours of light activity. Each additional 1 hour of moderate to vigorous activity was associated with a 14% increase in the likelihood of healthy aging. These findings support discussions with patients that behavior change, even in small increments, can be beneficial in healthy aging.
 

References

1. Xu W et al. Ann Intern Med. 2024 Jun;177(6):701-10.

2. Yourman LC et al. JAMA Intern Med. 2021;181:179-85.

3. Demay MB et al. J Clin Endocrinol Metab. August 2024;109(8):1907-47.

4. Shi H et al. JAMA Netw Open. 2024;7(6):e2416300.

In this article, I will review several recently published articles and guidelines relevant to the care of older adults in primary care. The articles of interest address statins for primary prevention, vitamin D supplementation and testing, and physical activity for healthy aging.
 

Statins for Primary Prevention of Cardiovascular Disease

A common conundrum in primary care is whether an older adult should be on a statin for primary prevention. This question has been difficult to answer because of the underrepresentation of older adults in clinical trials that examine the effect of statins for primary prevention. A recent study by Xu et al. published in Annals of Internal Medicine sought to address this gap in knowledge, investigating the risks and benefits of statins for primary prevention for older adults.¹

This study stratified participants by “old” (aged 75-84 years) and “very old” (85 years or older). In this study, older adults who had an indication for statins were initiated on statins and studied over a 5-year period and compared with age-matched cohorts not initiated on statin therapy. Participants with known cardiovascular disease at baseline were excluded. The outcomes of interest were major cardiovascular disease (CVD) (a composite of myocardial infarction, stroke, or heart failure), all-cause mortality, and adverse effect of drug therapy (myopathy or liver dysfunction).

The study found that among older adults aged 75-84, initiation of statin therapy led to a 1.2% risk reduction in major CVD over a 5-year period. For older adults aged 85 and greater, initiation of statins had an even larger impact, leading to a 4.4% risk reduction in major CVD over a 5-year period. The study found that there was no significant difference in adverse effects including myopathy or liver dysfunction in both age groups.

Statins, the study suggests, are appropriate and safe to initiate for primary prevention in older adults and can lead to substantial benefits in reduction of CVD. While time to benefit was not explicitly examined in this study, a prior study by Yourman et al. suggested that the time to benefit for statins for primary prevention in adults aged 50-75 would be least 2.5 years.²

My takeaway from these findings is to discuss statin initiation for primary prevention for older patients who are focused on longevity, have good functional status (often used in geriatrics as a proxy for prognosis), and are willing to accept more medications.
 

Empiric Vitamin D Supplementation in Adults over 75 Years

Vitamin D is one of the most common supplements taken by older adults but evidence supporting vitamin D supplementation is variable in published literature, as most data comes from observational trials. New guidelines from the Endocrine Society focused on developing recommendations for healthy individuals with data obtained from randomized controlled trials (RCTs) and large longitudinal observational trials with comparison groups if RCTs were not available. These guidelines recommend against empiric supplementation of vitamin D for healthy adults aged 18-74, excluding pregnant women and patients with high-risk diabetes.³

For older adults aged 75 or greater, empiric vitamin D supplementation is recommended because of the possible reduction of risk in all-cause mortality in this population. Of note, this was a grade 2 recommendation by the panel, indicating that the benefits of the treatment probably outweigh the risks. The panel stated that vitamin D supplementation could be delivered through fortified foods, multivitamins with vitamin D, or as a separate vitamin D supplement.

The dosage should remain within the recommended daily allowance outlined by the Institute of Medicine of 800 IU daily for adults over 70, and the panel recommends low-dose daily vitamin D supplementation over high-dose interval supplementation. The panel noted that routine screening of vitamin D levels should not be used to guide decision-making on whether to start supplementation, but vitamin D levels should be obtained for patients who have an indication for evaluation.

The reviewers highlight that these guidelines were developed for healthy individuals and are not applicable to those with conditions that warrant vitamin D evaluation. In my clinical practice, many of my patients have bone-mineral conditions and cognitive impairment that warrant evaluation. Based on these guidelines, I will consider empiric vitamin D supplementation more often for healthy patients aged 75 and older.
 

Sedentary Behaviors and Healthy Aging

Engaging inactive older adults in regular physical activity can be challenging, particularly as the pandemic has led to more pervasive social isolation and affected the availability of in-person exercise activities in the community. Physical activity is a key component of healthy aging and cognition, and its benefits should be a part of routine counseling for older adults.

An interesting recent study published in JAMA Network Open by Shi et al. evaluated the association of health behaviors and aging in female US nurses over a 20-year period.⁴ Surveys were administered to capture time spent in each behavior, such as being sedentary (TV watching, sitting at home or at work), light activity (walking around the house or at work), and moderate to vigorous activity (walking for exercise, lawn mowing). “Healthy aging” was defined by the absence of chronic conditions such as heart failure, and lack of physical, mental, and cognitive impairment.

The study found that participants who were more sedentary were less likely to age healthfully, with each additional 2 hours of TV watching per day associated with a 12% reduction in likelihood of healthy aging. Light physical activity was associated with a significant increase in healthy aging, with a 6% increase in the likelihood of healthy aging for each additional 2 hours of light activity. Each additional 1 hour of moderate to vigorous activity was associated with a 14% increase in the likelihood of healthy aging. These findings support discussions with patients that behavior change, even in small increments, can be beneficial in healthy aging.
 

References

1. Xu W et al. Ann Intern Med. 2024 Jun;177(6):701-10.

2. Yourman LC et al. JAMA Intern Med. 2021;181:179-85.

3. Demay MB et al. J Clin Endocrinol Metab. August 2024;109(8):1907-47.

4. Shi H et al. JAMA Netw Open. 2024;7(6):e2416300.

The drones are coming.

Starting in September, if someone in Clemmons, North Carolina, calls 911 to report a cardiac arrest, the first responder on the scene may be a drone carrying an automated external defibrillator, or AED.

“The idea is for the drone to get there several minutes before first responders,” such as an emergency medical technician or an ambulance, said Daniel Crews, a spokesperson for the sheriff’s office in Forsyth County, where Clemmons is located. The sheriff’s office is partnering on the project with local emergency services, the Clinical Research Institute at Duke University, and the drone consulting firm Hovecon. “The ultimate goal is to save lives and improve life expectancy for someone experiencing a cardiac episode,” Mr. Crews said.

The Forsyth County program is one of a growing number of efforts by public safety and healthcare organizations across the country to use drones to speed up lifesaving treatment in situations in which every second counts.

More than 356,000 people have a cardiac arrest outside of a hospital setting every year in the United States, according to the American Heart Association. Most people are at home when it happens, and about 90% die because they don’t get immediate help from first responders or bystanders. Every minute that passes without medical intervention decreases the odds of survival by 10%.

“We’ve never been able to move the needle for cardiac arrest in private settings, and this technology could meet that need,” said Monique Anderson Starks, MD, a cardiologist and associate professor of medicine at Duke University. Dr. Starks is leading pilot studies in Forsyth County and James City County, Virginia, to test whether drone AED delivery can improve treatment response times. The work is funded by a 4-year grant from the American Heart Association.

A 2017 study found it takes an emergency medical services unit 7 minutes, on average, to arrive on the scene following a 911 call, though response times vary considerably by region, and rural wait times can be much longer. Dr. Starks said she believes the drone-delivered AEDs in the pilot study could reduce the time to treatment by 4 minutes compared with first responders.

Unlike a heart attack, which occurs when blood flow to the heart is blocked, a cardiac arrest happens when a heart malfunction causes it to stop beating, typically because of an arrhythmia or an electrical problem. Eighty percent of cardiac arrests start as heart attacks. The only way to get the heart restarted is with CPR and a defibrillator.

In Forsyth County, a drone pilot from the sheriff’s department will listen in on 911 calls. If there’s a suspected cardiac arrest, the pilot can dispatch the drone even before emergency medical services are contacted. The drone, which weighs 22 pounds and can travel 60 mph, will fly to the location and hover 125 feet in the air before lowering an AED to the ground on a winch. The AED provides simple verbal instructions; the 911 dispatcher on the phone can also help a bystander use the AED.

Eventually there will be six drone bases in Forsyth and James City counties, Dr. Starks said.

While the technology is promising and research has often found that drones arrive faster than first responders, there’s little conclusive evidence that drones improve health outcomes.

A Swedish study published in The Lancet in 2023 compared the response times between drones and ambulances for suspected cardiac arrest in 58 deployments in an area of about 200,000 people. It found that drones beat the ambulance to the scene two thirds of the time, by a median of 3 minutes and 14 seconds.

In the United States, most programs are just getting started, and they are exploring the use of drones to also provide remedies for drug overdoses and major trauma or potential drowning rescues.

In Florida, Tampa General Hospital, Manatee County, and Archer First Response Systems, or AFRS, began a program in May to deliver AEDs, a tourniquet, and Narcan, a nasal spray that can reverse an opioid overdose. The program initially covers a 7-square-mile area, and EMS dispatchers deploy the drones, which are monitored by drone pilots.

There were nearly 108,000 drug overdose deaths in the United States in 2022, according to the National Institute on Drug Abuse.

As of early July, the Tampa program hadn’t yet deployed any drones, said Gordon Folkes, the founder and chief executive of AFRS, which develops and deploys emergency drone logistics systems. One request in June to send a drone to an overdose couldn’t be fulfilled because of a violent thunderstorm, Mr. Folkes said. In the testing area, which covers about 7,000 residents, Mr. Folkes estimates that 10-15 drones might be deployed each year.

“The bread and butter for these systems is suburban areas” like Manatee County that are well-populated and where the drones have the advantage of being able to avoid traffic congestion, Mr. Folkes said.

There are other uses for drones in medical emergencies. The New York Police Department plans to drop emergency flotation devices to struggling swimmers at local beaches. In Chula Vista, California, a police drone was able to pinpoint the location of a burning car, and then officers pulled the driver out, said Sgt. Tony Molina.

Rescue personnel have used drones to locate people who wander away from nursing homes, said James Augustine, a spokesperson for the American College of Emergency Physicians who is the medical director for the International Association of Fire Chiefs.

In the United States, one hurdle for drone programs is that the Federal Aviation Administration typically requires that drones be operated within the operators’ visual line of sight. In May, when Congress passed the FAA reauthorization bill, it gave the FAA 4 months to issue a notice of proposed rule-making on drone operations beyond the visual line of sight.

“The FAA is focused on developing standard rules to make [Beyond Visual Line of Sight] operations routine, scalable, and economically viable,” said Rick Breitenfeldt, an FAA spokesperson.

Some civil liberties groups are concerned that the FAA’s new rules may not provide enough protection from drone cameras for people on the ground.

Jay Stanley, a senior policy analyst at the American Civil Liberties Union, acknowledged the benefits of using drones in emergency situations but said there are issues that need to be addressed.

“The concern is that the FAA is going to significantly loosen the reins of drones without any significant privacy protections,” he said.

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF — the independent source for health policy research, polling, and journalism.

The drones are coming.

Starting in September, if someone in Clemmons, North Carolina, calls 911 to report a cardiac arrest, the first responder on the scene may be a drone carrying an automated external defibrillator, or AED.

“The idea is for the drone to get there several minutes before first responders,” such as an emergency medical technician or an ambulance, said Daniel Crews, a spokesperson for the sheriff’s office in Forsyth County, where Clemmons is located. The sheriff’s office is partnering on the project with local emergency services, the Clinical Research Institute at Duke University, and the drone consulting firm Hovecon. “The ultimate goal is to save lives and improve life expectancy for someone experiencing a cardiac episode,” Mr. Crews said.

The Forsyth County program is one of a growing number of efforts by public safety and healthcare organizations across the country to use drones to speed up lifesaving treatment in situations in which every second counts.

More than 356,000 people have a cardiac arrest outside of a hospital setting every year in the United States, according to the American Heart Association. Most people are at home when it happens, and about 90% die because they don’t get immediate help from first responders or bystanders. Every minute that passes without medical intervention decreases the odds of survival by 10%.

“We’ve never been able to move the needle for cardiac arrest in private settings, and this technology could meet that need,” said Monique Anderson Starks, MD, a cardiologist and associate professor of medicine at Duke University. Dr. Starks is leading pilot studies in Forsyth County and James City County, Virginia, to test whether drone AED delivery can improve treatment response times. The work is funded by a 4-year grant from the American Heart Association.

A 2017 study found it takes an emergency medical services unit 7 minutes, on average, to arrive on the scene following a 911 call, though response times vary considerably by region, and rural wait times can be much longer. Dr. Starks said she believes the drone-delivered AEDs in the pilot study could reduce the time to treatment by 4 minutes compared with first responders.

Unlike a heart attack, which occurs when blood flow to the heart is blocked, a cardiac arrest happens when a heart malfunction causes it to stop beating, typically because of an arrhythmia or an electrical problem. Eighty percent of cardiac arrests start as heart attacks. The only way to get the heart restarted is with CPR and a defibrillator.

In Forsyth County, a drone pilot from the sheriff’s department will listen in on 911 calls. If there’s a suspected cardiac arrest, the pilot can dispatch the drone even before emergency medical services are contacted. The drone, which weighs 22 pounds and can travel 60 mph, will fly to the location and hover 125 feet in the air before lowering an AED to the ground on a winch. The AED provides simple verbal instructions; the 911 dispatcher on the phone can also help a bystander use the AED.

Eventually there will be six drone bases in Forsyth and James City counties, Dr. Starks said.

While the technology is promising and research has often found that drones arrive faster than first responders, there’s little conclusive evidence that drones improve health outcomes.

A Swedish study published in The Lancet in 2023 compared the response times between drones and ambulances for suspected cardiac arrest in 58 deployments in an area of about 200,000 people. It found that drones beat the ambulance to the scene two thirds of the time, by a median of 3 minutes and 14 seconds.

In the United States, most programs are just getting started, and they are exploring the use of drones to also provide remedies for drug overdoses and major trauma or potential drowning rescues.

In Florida, Tampa General Hospital, Manatee County, and Archer First Response Systems, or AFRS, began a program in May to deliver AEDs, a tourniquet, and Narcan, a nasal spray that can reverse an opioid overdose. The program initially covers a 7-square-mile area, and EMS dispatchers deploy the drones, which are monitored by drone pilots.

There were nearly 108,000 drug overdose deaths in the United States in 2022, according to the National Institute on Drug Abuse.

As of early July, the Tampa program hadn’t yet deployed any drones, said Gordon Folkes, the founder and chief executive of AFRS, which develops and deploys emergency drone logistics systems. One request in June to send a drone to an overdose couldn’t be fulfilled because of a violent thunderstorm, Mr. Folkes said. In the testing area, which covers about 7,000 residents, Mr. Folkes estimates that 10-15 drones might be deployed each year.

“The bread and butter for these systems is suburban areas” like Manatee County that are well-populated and where the drones have the advantage of being able to avoid traffic congestion, Mr. Folkes said.

There are other uses for drones in medical emergencies. The New York Police Department plans to drop emergency flotation devices to struggling swimmers at local beaches. In Chula Vista, California, a police drone was able to pinpoint the location of a burning car, and then officers pulled the driver out, said Sgt. Tony Molina.

Rescue personnel have used drones to locate people who wander away from nursing homes, said James Augustine, a spokesperson for the American College of Emergency Physicians who is the medical director for the International Association of Fire Chiefs.

In the United States, one hurdle for drone programs is that the Federal Aviation Administration typically requires that drones be operated within the operators’ visual line of sight. In May, when Congress passed the FAA reauthorization bill, it gave the FAA 4 months to issue a notice of proposed rule-making on drone operations beyond the visual line of sight.

“The FAA is focused on developing standard rules to make [Beyond Visual Line of Sight] operations routine, scalable, and economically viable,” said Rick Breitenfeldt, an FAA spokesperson.

Some civil liberties groups are concerned that the FAA’s new rules may not provide enough protection from drone cameras for people on the ground.

Jay Stanley, a senior policy analyst at the American Civil Liberties Union, acknowledged the benefits of using drones in emergency situations but said there are issues that need to be addressed.

“The concern is that the FAA is going to significantly loosen the reins of drones without any significant privacy protections,” he said.

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF — the independent source for health policy research, polling, and journalism.

The drones are coming.

Starting in September, if someone in Clemmons, North Carolina, calls 911 to report a cardiac arrest, the first responder on the scene may be a drone carrying an automated external defibrillator, or AED.

“The idea is for the drone to get there several minutes before first responders,” such as an emergency medical technician or an ambulance, said Daniel Crews, a spokesperson for the sheriff’s office in Forsyth County, where Clemmons is located. The sheriff’s office is partnering on the project with local emergency services, the Clinical Research Institute at Duke University, and the drone consulting firm Hovecon. “The ultimate goal is to save lives and improve life expectancy for someone experiencing a cardiac episode,” Mr. Crews said.

The Forsyth County program is one of a growing number of efforts by public safety and healthcare organizations across the country to use drones to speed up lifesaving treatment in situations in which every second counts.

More than 356,000 people have a cardiac arrest outside of a hospital setting every year in the United States, according to the American Heart Association. Most people are at home when it happens, and about 90% die because they don’t get immediate help from first responders or bystanders. Every minute that passes without medical intervention decreases the odds of survival by 10%.

“We’ve never been able to move the needle for cardiac arrest in private settings, and this technology could meet that need,” said Monique Anderson Starks, MD, a cardiologist and associate professor of medicine at Duke University. Dr. Starks is leading pilot studies in Forsyth County and James City County, Virginia, to test whether drone AED delivery can improve treatment response times. The work is funded by a 4-year grant from the American Heart Association.

A 2017 study found it takes an emergency medical services unit 7 minutes, on average, to arrive on the scene following a 911 call, though response times vary considerably by region, and rural wait times can be much longer. Dr. Starks said she believes the drone-delivered AEDs in the pilot study could reduce the time to treatment by 4 minutes compared with first responders.

Unlike a heart attack, which occurs when blood flow to the heart is blocked, a cardiac arrest happens when a heart malfunction causes it to stop beating, typically because of an arrhythmia or an electrical problem. Eighty percent of cardiac arrests start as heart attacks. The only way to get the heart restarted is with CPR and a defibrillator.

In Forsyth County, a drone pilot from the sheriff’s department will listen in on 911 calls. If there’s a suspected cardiac arrest, the pilot can dispatch the drone even before emergency medical services are contacted. The drone, which weighs 22 pounds and can travel 60 mph, will fly to the location and hover 125 feet in the air before lowering an AED to the ground on a winch. The AED provides simple verbal instructions; the 911 dispatcher on the phone can also help a bystander use the AED.

Eventually there will be six drone bases in Forsyth and James City counties, Dr. Starks said.

While the technology is promising and research has often found that drones arrive faster than first responders, there’s little conclusive evidence that drones improve health outcomes.

A Swedish study published in The Lancet in 2023 compared the response times between drones and ambulances for suspected cardiac arrest in 58 deployments in an area of about 200,000 people. It found that drones beat the ambulance to the scene two thirds of the time, by a median of 3 minutes and 14 seconds.

In the United States, most programs are just getting started, and they are exploring the use of drones to also provide remedies for drug overdoses and major trauma or potential drowning rescues.

In Florida, Tampa General Hospital, Manatee County, and Archer First Response Systems, or AFRS, began a program in May to deliver AEDs, a tourniquet, and Narcan, a nasal spray that can reverse an opioid overdose. The program initially covers a 7-square-mile area, and EMS dispatchers deploy the drones, which are monitored by drone pilots.

There were nearly 108,000 drug overdose deaths in the United States in 2022, according to the National Institute on Drug Abuse.

As of early July, the Tampa program hadn’t yet deployed any drones, said Gordon Folkes, the founder and chief executive of AFRS, which develops and deploys emergency drone logistics systems. One request in June to send a drone to an overdose couldn’t be fulfilled because of a violent thunderstorm, Mr. Folkes said. In the testing area, which covers about 7,000 residents, Mr. Folkes estimates that 10-15 drones might be deployed each year.

“The bread and butter for these systems is suburban areas” like Manatee County that are well-populated and where the drones have the advantage of being able to avoid traffic congestion, Mr. Folkes said.

There are other uses for drones in medical emergencies. The New York Police Department plans to drop emergency flotation devices to struggling swimmers at local beaches. In Chula Vista, California, a police drone was able to pinpoint the location of a burning car, and then officers pulled the driver out, said Sgt. Tony Molina.

Rescue personnel have used drones to locate people who wander away from nursing homes, said James Augustine, a spokesperson for the American College of Emergency Physicians who is the medical director for the International Association of Fire Chiefs.

In the United States, one hurdle for drone programs is that the Federal Aviation Administration typically requires that drones be operated within the operators’ visual line of sight. In May, when Congress passed the FAA reauthorization bill, it gave the FAA 4 months to issue a notice of proposed rule-making on drone operations beyond the visual line of sight.

“The FAA is focused on developing standard rules to make [Beyond Visual Line of Sight] operations routine, scalable, and economically viable,” said Rick Breitenfeldt, an FAA spokesperson.

Some civil liberties groups are concerned that the FAA’s new rules may not provide enough protection from drone cameras for people on the ground.

Jay Stanley, a senior policy analyst at the American Civil Liberties Union, acknowledged the benefits of using drones in emergency situations but said there are issues that need to be addressed.

“The concern is that the FAA is going to significantly loosen the reins of drones without any significant privacy protections,” he said.

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF — the independent source for health policy research, polling, and journalism.

Pharmacist Mark Mikhael has lost 50 pounds over the past 12 months. He no longer has diabetes and finds himself “at my ideal body weight,” with his cholesterol below 200 for the first time in 20 years. “I feel fantastic,” he said.

Like millions of others, Mr. Mikhael credits the new class of weight loss drugs. But he isn’t using brand-name Wegovy or Zepbound. Mr. Mikhael, CEO of Orlando, Florida–based Olympia Pharmaceuticals, has been getting by with his own supply: injecting himself with copies of the drugs formulated by his company.

He’s far from alone. Mr. Mikhael and other industry officials estimate that several large compounding pharmacies like his are provisioning up to 2 million American patients with regular doses of semaglutide, the scientific name for Novo Nordisk’s Wegovy, Ozempic, and Rybelsus formulations, or tirzepatide, the active ingredient in Eli Lilly’s Zepbound and Mounjaro.

The drug-making behemoths fiercely oppose that compounding business. Novo Nordisk and Lilly lump the compounders together with Internet cowboys and unregulated medical spas peddling bogus semaglutide, and have high-powered legal teams trying to stop them. Novo Nordisk has filed at least 21 lawsuits nationwide against companies making purported copies of its drugs, said Brianna Kelley, a spokesperson for the company, and urges doctors to avoid them. The Food and Drug Administration (FDA), too, has cautioned about the potential danger of the compounds, and leading obesity medicine groups starkly warn patients against their use.

But this isn’t an illegal black market, though it has shades of gray.

The FDA allows and even encourages compounding pharmacies to produce and sell copycats when a drug is in short supply, and the wildly popular glucagon-like peptide 1 (GLP-1) drugs have enduring shortages — first reported in March 2022 for semaglutide and in December 2022 for tirzepatide. The drugs have registered unprecedented success in weight loss. They are also showing promise against heart, kidney, and liver diseases and are being tested against conditions as diverse as Alzheimer’s disease and drug addiction.

In recent years, the US health care system has come to depend on compounding pharmacies, many of which are run as nonprofits, to plug supply holes of crucial drugs like cancer medicines cisplatin, methotrexate, and 5-fluorouracil.

Most compounded drugs are old, cheap generics. Semaglutide and tirzepatide, on the other hand, are under patent and earn Novo Nordisk and Lilly billions of dollars a year. Sales of the diabetes and weight loss drugs in 2024 made Novo Nordisk Europe’s most valuable company and Lilly the world’s biggest pharmaceutical company.

While the companies can’t keep up with demand, they heatedly dispute the right of compounders to make and sell copies. Lilly spokesperson Kristiane Silva Bello said her company was “deeply concerned” about “serious health risks” from compounded drugs that “should not be on the market.”

Yet marketed they are. Even Hims & Hers Health — the telemedicine prescriber that got its start with erectile dysfunction drugs — is now peddling compounded semaglutide. It ran ads for the drugs during NBA playoff games. (According to a Hunterbrook Media report, Hims & Hers’ semaglutide supplier has faced legal scrutiny.)

The compounded forms are significantly cheaper than the branded drugs. Patients pay about $100-$450 a month, compared with list prices of roughly $1,000-$1,400 for Lilly and Novo Nordisk products.

Five compounders and distributors interviewed for this article said they conduct due diligence on every lot of semaglutide or tirzepatide they buy or produce, upholding standards of purity, sterility, and consistency similar to those practiced in the commercial drug industry. Compounders operate under strict federal and state standards, they noted.

However, the raw materials used in the compounded forms may differ from those produced for Novo Nordisk and Lilly, said GLP-1 coinventor Jens Juul Holst, of the University of Copenhagen, adding that care must be taken in drug production lest it cause potentially harmful immune reactions.

To date, according to FDA spokespeople, reports of side effects from taking compounded versions haven’t raised major alarms. But everyone with knowledge of the industry, including the compounders themselves, worry that a single batch of a poorly made drug could kill or maim people and destroy confidence in their business.

“I liken the compounding industry to the airline industry,” Mr. Mikhael said. “When you have an airline crash, it hurts everybody.”
 

Warnings From the Past

The industry endured just such a catastrophe in 2012, when the New England Compounding Center released a contaminated injectable steroid that killed at least 64 people and harmed hundreds more.

In response, Congress and the FDA had strengthened oversight. Mr. Mikhael’s company is an outsourcing facility, or 503B compounding pharmacy — so-named for a section of the 2013 law that set new requirements for drug compounders. The companies are licensed to make slightly different versions of FDA-approved drugs in response to shortages or a patient’s special needs.

The law created two classes of compounding pharmacies: The FDA regulates the larger 503B compounders with standards like commercial drug companies, while 503A pharmacies make smaller lots of drugs and are largely overseen by state boards of pharmacy.

The 503A facilities also are producing compounded semaglutide and tirzepatide for hundreds of thousands of patients. Like the 503Bs, these operations take the active ingredient, produced as a powder in FDA-registered factories, mostly in China, then reconstitute it with sterile water and an antimicrobial in small glass vials.

Together, the compounding pharmacies may account for up to 30% of the semaglutide sold in the United States, Mr. Mikhael said, although he cautions that is a “wild ballpark figure” since no one, including the FDA, is tracking sales in the industry.

The compounders say the companies should increase production if they’re worried about competition. Like the dozens of other drugs they produce for hospitals and medical practices, the compounders say, the two diet drugs are essential products.

“If you don’t want a 503B facility to make a copy, it’s pretty simple: Don’t go short,” said Lee Rosebush, chair of a trade association for 503B pharmacies. “FDA created this system because these are necessary drugs.”

Novo Nordisk hasn’t specified why it can’t keep up with demand, but the bottleneck apparently lies in the company’s inability to fill and sterilize enough of its special drug auto-injectors, said Evan Seigerman, a managing director at BMO Capital Markets.

The company announced June 24 that it was investing $4.1 billion in new production lines at its Clayton, North Carolina, site. In 2023, the FDA issued a warning over procedural violations at the site and separate cautions at an Indiana facility that Novo Nordisk took over recently.
 

Compounding for Dummies

At least 28 companies, mostly in China, are registered with the FDA to produce or distribute semaglutide. At least half the companies have entered the market in the past 12 months, driving the raw material’s price down by 35%, according to Scott Welch, who runs a 503A pharmacy in Arlington, Virginia.

Compounders can buy powdered semaglutide from some US distributors for less than $4,000 a gram, said Matthew Johnson, president and CEO of distributor Pharma Source Direct. That comes out to as little as $10 per weekly 2.5-microgram dose – not including overhead and other costs.

While Ozempic or Wegovy patients use a Novo Nordisk device to inject the drug, patients using compounded products draw them from a vial with a small needle, like the device diabetics use for insulin.

Some medical practices provide the compounded drug to patients as part of a weight loss package, with markups. In July 2023, Tabitha Ries, a single mother of six who works as a home health care aide in Garfield, Washington, found an online clinic that charged her $1,000 for 3 months of semaglutide along with counseling. She has lost 35 pounds.

She gets the drug from Mindful Weight Loss, a mostly telehealth-based operation led by physician Vivek Gupta, MD, of Manhattan Beach, California. Dr. Gupta said he’s prescribed the weight loss drugs to 1,500 patients, with about 60% using compounded versions from a 503A pharmacy.

He hasn’t seen any essential difference in patients using the branded and compounded forms, although “some people say the compounding is a little less effective,” Dr. Gupta said.

There’s some risk in using the non–FDA-approved product, he acknowledged, and he requires patients to sign an informed consent waiver.

“Nothing in life is without risk, but I would also argue that the status quo is not safe for people who need the medicine and can’t get it,” he said. “They’re constantly triggered by all this food that’s causing their weight to go up and their sugar to go high, increasing their insulin resistance and affecting their limbs and eyes.”

Compounding semaglutide is a helpful sideline for pharmacists like him, Mr. Welch said, especially given the pinch on drug sale revenue that has led many independents to close in recent years. He figures he earns 95% of his revenue from compounding drugs, rather than traditional prescriptions.

It’s important to distinguish compounded semaglutide from unregulated powders sold as “generic Ozempic” and the like, which may be contaminated or counterfeit, said FDA spokesperson Amanda Hils. But since compounded forms of the drug are not FDA approved, those who make, prescribe, or use them also should have “an increased level of responsibility or awareness,” she said.
 

Corporate Battles

Novo Nordisk and Lilly, in lawsuits each company has filed against competitors, say their own testing has found bacteria and other impurities in products made by compounding pharmacies. The companies also report patent infringement, but compounders, pointing to the FDA loophole for drugs in shortage, appear to have defeated that argument for now.

When the FDA removes the drugs from the shortage list, 503B compounders must immediately stop selling them. Smaller compounders may be able to produce their products for a reduced number of patients, said Scott Brunner, CEO of the Alliance for Pharmacy Compounding, which represents 503A compounders.

The evaporation of the compounded drug supply could come as a shock to patients.

“I dread it,” said David Wertheimer, an internist in Franklin Lakes, New Jersey, who prescribes compounded semaglutide to some patients. “People are not going to be able to plunk down a grand every month. A lot of people will go off the drug, and that’s a shame.”

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF—an independent source of health policy research, polling, and journalism. Learn more about KFF.

Pharmacist Mark Mikhael has lost 50 pounds over the past 12 months. He no longer has diabetes and finds himself “at my ideal body weight,” with his cholesterol below 200 for the first time in 20 years. “I feel fantastic,” he said.

Like millions of others, Mr. Mikhael credits the new class of weight loss drugs. But he isn’t using brand-name Wegovy or Zepbound. Mr. Mikhael, CEO of Orlando, Florida–based Olympia Pharmaceuticals, has been getting by with his own supply: injecting himself with copies of the drugs formulated by his company.

He’s far from alone. Mr. Mikhael and other industry officials estimate that several large compounding pharmacies like his are provisioning up to 2 million American patients with regular doses of semaglutide, the scientific name for Novo Nordisk’s Wegovy, Ozempic, and Rybelsus formulations, or tirzepatide, the active ingredient in Eli Lilly’s Zepbound and Mounjaro.

The drug-making behemoths fiercely oppose that compounding business. Novo Nordisk and Lilly lump the compounders together with Internet cowboys and unregulated medical spas peddling bogus semaglutide, and have high-powered legal teams trying to stop them. Novo Nordisk has filed at least 21 lawsuits nationwide against companies making purported copies of its drugs, said Brianna Kelley, a spokesperson for the company, and urges doctors to avoid them. The Food and Drug Administration (FDA), too, has cautioned about the potential danger of the compounds, and leading obesity medicine groups starkly warn patients against their use.

But this isn’t an illegal black market, though it has shades of gray.

The FDA allows and even encourages compounding pharmacies to produce and sell copycats when a drug is in short supply, and the wildly popular glucagon-like peptide 1 (GLP-1) drugs have enduring shortages — first reported in March 2022 for semaglutide and in December 2022 for tirzepatide. The drugs have registered unprecedented success in weight loss. They are also showing promise against heart, kidney, and liver diseases and are being tested against conditions as diverse as Alzheimer’s disease and drug addiction.

In recent years, the US health care system has come to depend on compounding pharmacies, many of which are run as nonprofits, to plug supply holes of crucial drugs like cancer medicines cisplatin, methotrexate, and 5-fluorouracil.

Most compounded drugs are old, cheap generics. Semaglutide and tirzepatide, on the other hand, are under patent and earn Novo Nordisk and Lilly billions of dollars a year. Sales of the diabetes and weight loss drugs in 2024 made Novo Nordisk Europe’s most valuable company and Lilly the world’s biggest pharmaceutical company.

While the companies can’t keep up with demand, they heatedly dispute the right of compounders to make and sell copies. Lilly spokesperson Kristiane Silva Bello said her company was “deeply concerned” about “serious health risks” from compounded drugs that “should not be on the market.”

Yet marketed they are. Even Hims & Hers Health — the telemedicine prescriber that got its start with erectile dysfunction drugs — is now peddling compounded semaglutide. It ran ads for the drugs during NBA playoff games. (According to a Hunterbrook Media report, Hims & Hers’ semaglutide supplier has faced legal scrutiny.)

The compounded forms are significantly cheaper than the branded drugs. Patients pay about $100-$450 a month, compared with list prices of roughly $1,000-$1,400 for Lilly and Novo Nordisk products.

Five compounders and distributors interviewed for this article said they conduct due diligence on every lot of semaglutide or tirzepatide they buy or produce, upholding standards of purity, sterility, and consistency similar to those practiced in the commercial drug industry. Compounders operate under strict federal and state standards, they noted.

However, the raw materials used in the compounded forms may differ from those produced for Novo Nordisk and Lilly, said GLP-1 coinventor Jens Juul Holst, of the University of Copenhagen, adding that care must be taken in drug production lest it cause potentially harmful immune reactions.

To date, according to FDA spokespeople, reports of side effects from taking compounded versions haven’t raised major alarms. But everyone with knowledge of the industry, including the compounders themselves, worry that a single batch of a poorly made drug could kill or maim people and destroy confidence in their business.

“I liken the compounding industry to the airline industry,” Mr. Mikhael said. “When you have an airline crash, it hurts everybody.”
 

Warnings From the Past

The industry endured just such a catastrophe in 2012, when the New England Compounding Center released a contaminated injectable steroid that killed at least 64 people and harmed hundreds more.

In response, Congress and the FDA had strengthened oversight. Mr. Mikhael’s company is an outsourcing facility, or 503B compounding pharmacy — so-named for a section of the 2013 law that set new requirements for drug compounders. The companies are licensed to make slightly different versions of FDA-approved drugs in response to shortages or a patient’s special needs.

The law created two classes of compounding pharmacies: The FDA regulates the larger 503B compounders with standards like commercial drug companies, while 503A pharmacies make smaller lots of drugs and are largely overseen by state boards of pharmacy.

The 503A facilities also are producing compounded semaglutide and tirzepatide for hundreds of thousands of patients. Like the 503Bs, these operations take the active ingredient, produced as a powder in FDA-registered factories, mostly in China, then reconstitute it with sterile water and an antimicrobial in small glass vials.

Together, the compounding pharmacies may account for up to 30% of the semaglutide sold in the United States, Mr. Mikhael said, although he cautions that is a “wild ballpark figure” since no one, including the FDA, is tracking sales in the industry.

The compounders say the companies should increase production if they’re worried about competition. Like the dozens of other drugs they produce for hospitals and medical practices, the compounders say, the two diet drugs are essential products.

“If you don’t want a 503B facility to make a copy, it’s pretty simple: Don’t go short,” said Lee Rosebush, chair of a trade association for 503B pharmacies. “FDA created this system because these are necessary drugs.”

Novo Nordisk hasn’t specified why it can’t keep up with demand, but the bottleneck apparently lies in the company’s inability to fill and sterilize enough of its special drug auto-injectors, said Evan Seigerman, a managing director at BMO Capital Markets.

The company announced June 24 that it was investing $4.1 billion in new production lines at its Clayton, North Carolina, site. In 2023, the FDA issued a warning over procedural violations at the site and separate cautions at an Indiana facility that Novo Nordisk took over recently.
 

Compounding for Dummies

At least 28 companies, mostly in China, are registered with the FDA to produce or distribute semaglutide. At least half the companies have entered the market in the past 12 months, driving the raw material’s price down by 35%, according to Scott Welch, who runs a 503A pharmacy in Arlington, Virginia.

Compounders can buy powdered semaglutide from some US distributors for less than $4,000 a gram, said Matthew Johnson, president and CEO of distributor Pharma Source Direct. That comes out to as little as $10 per weekly 2.5-microgram dose – not including overhead and other costs.

While Ozempic or Wegovy patients use a Novo Nordisk device to inject the drug, patients using compounded products draw them from a vial with a small needle, like the device diabetics use for insulin.

Some medical practices provide the compounded drug to patients as part of a weight loss package, with markups. In July 2023, Tabitha Ries, a single mother of six who works as a home health care aide in Garfield, Washington, found an online clinic that charged her $1,000 for 3 months of semaglutide along with counseling. She has lost 35 pounds.

She gets the drug from Mindful Weight Loss, a mostly telehealth-based operation led by physician Vivek Gupta, MD, of Manhattan Beach, California. Dr. Gupta said he’s prescribed the weight loss drugs to 1,500 patients, with about 60% using compounded versions from a 503A pharmacy.

He hasn’t seen any essential difference in patients using the branded and compounded forms, although “some people say the compounding is a little less effective,” Dr. Gupta said.

There’s some risk in using the non–FDA-approved product, he acknowledged, and he requires patients to sign an informed consent waiver.

“Nothing in life is without risk, but I would also argue that the status quo is not safe for people who need the medicine and can’t get it,” he said. “They’re constantly triggered by all this food that’s causing their weight to go up and their sugar to go high, increasing their insulin resistance and affecting their limbs and eyes.”

Compounding semaglutide is a helpful sideline for pharmacists like him, Mr. Welch said, especially given the pinch on drug sale revenue that has led many independents to close in recent years. He figures he earns 95% of his revenue from compounding drugs, rather than traditional prescriptions.

It’s important to distinguish compounded semaglutide from unregulated powders sold as “generic Ozempic” and the like, which may be contaminated or counterfeit, said FDA spokesperson Amanda Hils. But since compounded forms of the drug are not FDA approved, those who make, prescribe, or use them also should have “an increased level of responsibility or awareness,” she said.
 

Corporate Battles

Novo Nordisk and Lilly, in lawsuits each company has filed against competitors, say their own testing has found bacteria and other impurities in products made by compounding pharmacies. The companies also report patent infringement, but compounders, pointing to the FDA loophole for drugs in shortage, appear to have defeated that argument for now.

When the FDA removes the drugs from the shortage list, 503B compounders must immediately stop selling them. Smaller compounders may be able to produce their products for a reduced number of patients, said Scott Brunner, CEO of the Alliance for Pharmacy Compounding, which represents 503A compounders.

The evaporation of the compounded drug supply could come as a shock to patients.

“I dread it,” said David Wertheimer, an internist in Franklin Lakes, New Jersey, who prescribes compounded semaglutide to some patients. “People are not going to be able to plunk down a grand every month. A lot of people will go off the drug, and that’s a shame.”

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF—an independent source of health policy research, polling, and journalism. Learn more about KFF.

Pharmacist Mark Mikhael has lost 50 pounds over the past 12 months. He no longer has diabetes and finds himself “at my ideal body weight,” with his cholesterol below 200 for the first time in 20 years. “I feel fantastic,” he said.

Like millions of others, Mr. Mikhael credits the new class of weight loss drugs. But he isn’t using brand-name Wegovy or Zepbound. Mr. Mikhael, CEO of Orlando, Florida–based Olympia Pharmaceuticals, has been getting by with his own supply: injecting himself with copies of the drugs formulated by his company.

He’s far from alone. Mr. Mikhael and other industry officials estimate that several large compounding pharmacies like his are provisioning up to 2 million American patients with regular doses of semaglutide, the scientific name for Novo Nordisk’s Wegovy, Ozempic, and Rybelsus formulations, or tirzepatide, the active ingredient in Eli Lilly’s Zepbound and Mounjaro.

The drug-making behemoths fiercely oppose that compounding business. Novo Nordisk and Lilly lump the compounders together with Internet cowboys and unregulated medical spas peddling bogus semaglutide, and have high-powered legal teams trying to stop them. Novo Nordisk has filed at least 21 lawsuits nationwide against companies making purported copies of its drugs, said Brianna Kelley, a spokesperson for the company, and urges doctors to avoid them. The Food and Drug Administration (FDA), too, has cautioned about the potential danger of the compounds, and leading obesity medicine groups starkly warn patients against their use.

But this isn’t an illegal black market, though it has shades of gray.

The FDA allows and even encourages compounding pharmacies to produce and sell copycats when a drug is in short supply, and the wildly popular glucagon-like peptide 1 (GLP-1) drugs have enduring shortages — first reported in March 2022 for semaglutide and in December 2022 for tirzepatide. The drugs have registered unprecedented success in weight loss. They are also showing promise against heart, kidney, and liver diseases and are being tested against conditions as diverse as Alzheimer’s disease and drug addiction.

In recent years, the US health care system has come to depend on compounding pharmacies, many of which are run as nonprofits, to plug supply holes of crucial drugs like cancer medicines cisplatin, methotrexate, and 5-fluorouracil.

Most compounded drugs are old, cheap generics. Semaglutide and tirzepatide, on the other hand, are under patent and earn Novo Nordisk and Lilly billions of dollars a year. Sales of the diabetes and weight loss drugs in 2024 made Novo Nordisk Europe’s most valuable company and Lilly the world’s biggest pharmaceutical company.

While the companies can’t keep up with demand, they heatedly dispute the right of compounders to make and sell copies. Lilly spokesperson Kristiane Silva Bello said her company was “deeply concerned” about “serious health risks” from compounded drugs that “should not be on the market.”

Yet marketed they are. Even Hims & Hers Health — the telemedicine prescriber that got its start with erectile dysfunction drugs — is now peddling compounded semaglutide. It ran ads for the drugs during NBA playoff games. (According to a Hunterbrook Media report, Hims & Hers’ semaglutide supplier has faced legal scrutiny.)

The compounded forms are significantly cheaper than the branded drugs. Patients pay about $100-$450 a month, compared with list prices of roughly $1,000-$1,400 for Lilly and Novo Nordisk products.

Five compounders and distributors interviewed for this article said they conduct due diligence on every lot of semaglutide or tirzepatide they buy or produce, upholding standards of purity, sterility, and consistency similar to those practiced in the commercial drug industry. Compounders operate under strict federal and state standards, they noted.

However, the raw materials used in the compounded forms may differ from those produced for Novo Nordisk and Lilly, said GLP-1 coinventor Jens Juul Holst, of the University of Copenhagen, adding that care must be taken in drug production lest it cause potentially harmful immune reactions.

To date, according to FDA spokespeople, reports of side effects from taking compounded versions haven’t raised major alarms. But everyone with knowledge of the industry, including the compounders themselves, worry that a single batch of a poorly made drug could kill or maim people and destroy confidence in their business.

“I liken the compounding industry to the airline industry,” Mr. Mikhael said. “When you have an airline crash, it hurts everybody.”
 

Warnings From the Past

The industry endured just such a catastrophe in 2012, when the New England Compounding Center released a contaminated injectable steroid that killed at least 64 people and harmed hundreds more.

In response, Congress and the FDA had strengthened oversight. Mr. Mikhael’s company is an outsourcing facility, or 503B compounding pharmacy — so-named for a section of the 2013 law that set new requirements for drug compounders. The companies are licensed to make slightly different versions of FDA-approved drugs in response to shortages or a patient’s special needs.

The law created two classes of compounding pharmacies: The FDA regulates the larger 503B compounders with standards like commercial drug companies, while 503A pharmacies make smaller lots of drugs and are largely overseen by state boards of pharmacy.

The 503A facilities also are producing compounded semaglutide and tirzepatide for hundreds of thousands of patients. Like the 503Bs, these operations take the active ingredient, produced as a powder in FDA-registered factories, mostly in China, then reconstitute it with sterile water and an antimicrobial in small glass vials.

Together, the compounding pharmacies may account for up to 30% of the semaglutide sold in the United States, Mr. Mikhael said, although he cautions that is a “wild ballpark figure” since no one, including the FDA, is tracking sales in the industry.

The compounders say the companies should increase production if they’re worried about competition. Like the dozens of other drugs they produce for hospitals and medical practices, the compounders say, the two diet drugs are essential products.

“If you don’t want a 503B facility to make a copy, it’s pretty simple: Don’t go short,” said Lee Rosebush, chair of a trade association for 503B pharmacies. “FDA created this system because these are necessary drugs.”

Novo Nordisk hasn’t specified why it can’t keep up with demand, but the bottleneck apparently lies in the company’s inability to fill and sterilize enough of its special drug auto-injectors, said Evan Seigerman, a managing director at BMO Capital Markets.

The company announced June 24 that it was investing $4.1 billion in new production lines at its Clayton, North Carolina, site. In 2023, the FDA issued a warning over procedural violations at the site and separate cautions at an Indiana facility that Novo Nordisk took over recently.
 

Compounding for Dummies

At least 28 companies, mostly in China, are registered with the FDA to produce or distribute semaglutide. At least half the companies have entered the market in the past 12 months, driving the raw material’s price down by 35%, according to Scott Welch, who runs a 503A pharmacy in Arlington, Virginia.

Compounders can buy powdered semaglutide from some US distributors for less than $4,000 a gram, said Matthew Johnson, president and CEO of distributor Pharma Source Direct. That comes out to as little as $10 per weekly 2.5-microgram dose – not including overhead and other costs.

While Ozempic or Wegovy patients use a Novo Nordisk device to inject the drug, patients using compounded products draw them from a vial with a small needle, like the device diabetics use for insulin.

Some medical practices provide the compounded drug to patients as part of a weight loss package, with markups. In July 2023, Tabitha Ries, a single mother of six who works as a home health care aide in Garfield, Washington, found an online clinic that charged her $1,000 for 3 months of semaglutide along with counseling. She has lost 35 pounds.

She gets the drug from Mindful Weight Loss, a mostly telehealth-based operation led by physician Vivek Gupta, MD, of Manhattan Beach, California. Dr. Gupta said he’s prescribed the weight loss drugs to 1,500 patients, with about 60% using compounded versions from a 503A pharmacy.

He hasn’t seen any essential difference in patients using the branded and compounded forms, although “some people say the compounding is a little less effective,” Dr. Gupta said.

There’s some risk in using the non–FDA-approved product, he acknowledged, and he requires patients to sign an informed consent waiver.

“Nothing in life is without risk, but I would also argue that the status quo is not safe for people who need the medicine and can’t get it,” he said. “They’re constantly triggered by all this food that’s causing their weight to go up and their sugar to go high, increasing their insulin resistance and affecting their limbs and eyes.”

Compounding semaglutide is a helpful sideline for pharmacists like him, Mr. Welch said, especially given the pinch on drug sale revenue that has led many independents to close in recent years. He figures he earns 95% of his revenue from compounding drugs, rather than traditional prescriptions.

It’s important to distinguish compounded semaglutide from unregulated powders sold as “generic Ozempic” and the like, which may be contaminated or counterfeit, said FDA spokesperson Amanda Hils. But since compounded forms of the drug are not FDA approved, those who make, prescribe, or use them also should have “an increased level of responsibility or awareness,” she said.
 

Corporate Battles

Novo Nordisk and Lilly, in lawsuits each company has filed against competitors, say their own testing has found bacteria and other impurities in products made by compounding pharmacies. The companies also report patent infringement, but compounders, pointing to the FDA loophole for drugs in shortage, appear to have defeated that argument for now.

When the FDA removes the drugs from the shortage list, 503B compounders must immediately stop selling them. Smaller compounders may be able to produce their products for a reduced number of patients, said Scott Brunner, CEO of the Alliance for Pharmacy Compounding, which represents 503A compounders.

The evaporation of the compounded drug supply could come as a shock to patients.

“I dread it,” said David Wertheimer, an internist in Franklin Lakes, New Jersey, who prescribes compounded semaglutide to some patients. “People are not going to be able to plunk down a grand every month. A lot of people will go off the drug, and that’s a shame.”

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF—an independent source of health policy research, polling, and journalism. Learn more about KFF.

Everyone takes a pharmacology class in medical school that includes a lecture on beta receptors. They’re in the heart (beta-1) and lungs (beta-2), and drug compounds agonize or antagonize one or both. The professor will caution against using antagonists (beta blockade) for patients with chronic obstructive pulmonary disease (COPD) lest they further impair the patient’s irreversibly narrowed airways. Obsequious students mature into obsequious doctors, intent on “doing no harm.” For better or worse, you withhold beta-blockers from your patient with COPD and comorbid cardiac disease.

Perhaps because the pulmonologist isn’t usually the one who decides whether a beta-blocker is prescribed, I’ve been napping on this topic since training. Early in fellowship, I read an ACP Journal Club article about a Cochrane systematic review (yes, I read a review of a review) that concluded that beta-blockers are fine in patients with COPD. The summary appealed to my bias towards evidence-based medicine (EBM) supplanting physiology, medical school, and everything else. I was more apt to believe my stodgy residency attendings than the stodgy pharmacology professor. Even though COPD and cardiovascular disease share multiple risk factors, I had never reinvestigated the relationship between beta-blockers and COPD.

Turns out that while I was sleeping, the debate continued. Go figure. Just last month a prospective, observational study published in JAMA Network Open found that beta-blockers did not increase the risk for cardiovascular or respiratory events among patients with COPD being discharged after hospitalization for acute myocardial infarction. Although this could be viewed as a triumph for EBM over physiology and a validation of my decade-plus of intellectual laziness, the results are actually pretty thin. These studies, in which patients with an indication for a therapy (a beta-blocker in this case) are analyzed by whether or not they received it, are problematic. The fanciest statistics — in this case, they used propensity scores — can’t control for residual confounding. What drove the physicians to prescribe in some cases but not others? We can only guess.

This might be okay if there hadn’t been a randomized controlled trial (RCT) published in 2019 in The New England Journal of Medicine that found that beta-blockers increase the risk for severe COPD exacerbations. In EBM, the RCT trumps all. Ironically, this trial was designed to test whether beta-blockers reduce severe COPD exacerbations. Yes, we’d come full circle. There was enough biologic plausibility to support a positive effect, or so thought the study authors and the Department of Defense (DOD) — for reasons I can’t possibly guess, the DOD funded this RCT. My pharmacology professor must be rolling over in his tenure.

The RCT did leave beta-blockers some wiggle room. The authors purposely excluded anyone with a cardiovascular indication for a beta-blocker. The intent was to ensure beneficial effects were isolated to respiratory and not cardiovascular outcomes. Of course, the reason I’m writing and you’re reading this is that COPD and cardiovascular disease co-occur at a high rate. The RCT notwithstanding, we prescribe beta-blockers to patients with COPD because they have a cardiac indication, not to reduce acute COPD exacerbations. So, it’s possible there’d be a net beta-blocker benefit in patients with COPD and comorbid heart disease.

That’s where the JAMA Network Open study comes in, but as discussed, methodologic weaknesses preclude its being the final word. That said, I think it’s unlikely we’ll see a COPD with comorbid cardiac disease RCT performed to assess whether beta-blockers provide a net benefit, unless maybe the DOD wants to fund another one of these. In the meantime, I’m calling clinical equipoise and punting. Fortunately for me, I don’t have to prescribe beta-blockers. I suppose I could consider stopping them in my patient with severe COPD, the one I can’t keep out of the hospital, but I’m not convinced that would make much difference.
 

Dr. Holley is professor of medicine at Uniformed Services University in Bethesda, Maryland, and a pulmonary/sleep and critical care medicine physician at MedStar Washington Hospital Center in Washington, DC. He reported conflicts of interest with Metapharm, CHEST College, and WebMD.

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

Everyone takes a pharmacology class in medical school that includes a lecture on beta receptors. They’re in the heart (beta-1) and lungs (beta-2), and drug compounds agonize or antagonize one or both. The professor will caution against using antagonists (beta blockade) for patients with chronic obstructive pulmonary disease (COPD) lest they further impair the patient’s irreversibly narrowed airways. Obsequious students mature into obsequious doctors, intent on “doing no harm.” For better or worse, you withhold beta-blockers from your patient with COPD and comorbid cardiac disease.

Perhaps because the pulmonologist isn’t usually the one who decides whether a beta-blocker is prescribed, I’ve been napping on this topic since training. Early in fellowship, I read an ACP Journal Club article about a Cochrane systematic review (yes, I read a review of a review) that concluded that beta-blockers are fine in patients with COPD. The summary appealed to my bias towards evidence-based medicine (EBM) supplanting physiology, medical school, and everything else. I was more apt to believe my stodgy residency attendings than the stodgy pharmacology professor. Even though COPD and cardiovascular disease share multiple risk factors, I had never reinvestigated the relationship between beta-blockers and COPD.

Turns out that while I was sleeping, the debate continued. Go figure. Just last month a prospective, observational study published in JAMA Network Open found that beta-blockers did not increase the risk for cardiovascular or respiratory events among patients with COPD being discharged after hospitalization for acute myocardial infarction. Although this could be viewed as a triumph for EBM over physiology and a validation of my decade-plus of intellectual laziness, the results are actually pretty thin. These studies, in which patients with an indication for a therapy (a beta-blocker in this case) are analyzed by whether or not they received it, are problematic. The fanciest statistics — in this case, they used propensity scores — can’t control for residual confounding. What drove the physicians to prescribe in some cases but not others? We can only guess.

This might be okay if there hadn’t been a randomized controlled trial (RCT) published in 2019 in The New England Journal of Medicine that found that beta-blockers increase the risk for severe COPD exacerbations. In EBM, the RCT trumps all. Ironically, this trial was designed to test whether beta-blockers reduce severe COPD exacerbations. Yes, we’d come full circle. There was enough biologic plausibility to support a positive effect, or so thought the study authors and the Department of Defense (DOD) — for reasons I can’t possibly guess, the DOD funded this RCT. My pharmacology professor must be rolling over in his tenure.

The RCT did leave beta-blockers some wiggle room. The authors purposely excluded anyone with a cardiovascular indication for a beta-blocker. The intent was to ensure beneficial effects were isolated to respiratory and not cardiovascular outcomes. Of course, the reason I’m writing and you’re reading this is that COPD and cardiovascular disease co-occur at a high rate. The RCT notwithstanding, we prescribe beta-blockers to patients with COPD because they have a cardiac indication, not to reduce acute COPD exacerbations. So, it’s possible there’d be a net beta-blocker benefit in patients with COPD and comorbid heart disease.

That’s where the JAMA Network Open study comes in, but as discussed, methodologic weaknesses preclude its being the final word. That said, I think it’s unlikely we’ll see a COPD with comorbid cardiac disease RCT performed to assess whether beta-blockers provide a net benefit, unless maybe the DOD wants to fund another one of these. In the meantime, I’m calling clinical equipoise and punting. Fortunately for me, I don’t have to prescribe beta-blockers. I suppose I could consider stopping them in my patient with severe COPD, the one I can’t keep out of the hospital, but I’m not convinced that would make much difference.
 

Dr. Holley is professor of medicine at Uniformed Services University in Bethesda, Maryland, and a pulmonary/sleep and critical care medicine physician at MedStar Washington Hospital Center in Washington, DC. He reported conflicts of interest with Metapharm, CHEST College, and WebMD.

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

Everyone takes a pharmacology class in medical school that includes a lecture on beta receptors. They’re in the heart (beta-1) and lungs (beta-2), and drug compounds agonize or antagonize one or both. The professor will caution against using antagonists (beta blockade) for patients with chronic obstructive pulmonary disease (COPD) lest they further impair the patient’s irreversibly narrowed airways. Obsequious students mature into obsequious doctors, intent on “doing no harm.” For better or worse, you withhold beta-blockers from your patient with COPD and comorbid cardiac disease.

Perhaps because the pulmonologist isn’t usually the one who decides whether a beta-blocker is prescribed, I’ve been napping on this topic since training. Early in fellowship, I read an ACP Journal Club article about a Cochrane systematic review (yes, I read a review of a review) that concluded that beta-blockers are fine in patients with COPD. The summary appealed to my bias towards evidence-based medicine (EBM) supplanting physiology, medical school, and everything else. I was more apt to believe my stodgy residency attendings than the stodgy pharmacology professor. Even though COPD and cardiovascular disease share multiple risk factors, I had never reinvestigated the relationship between beta-blockers and COPD.

Turns out that while I was sleeping, the debate continued. Go figure. Just last month a prospective, observational study published in JAMA Network Open found that beta-blockers did not increase the risk for cardiovascular or respiratory events among patients with COPD being discharged after hospitalization for acute myocardial infarction. Although this could be viewed as a triumph for EBM over physiology and a validation of my decade-plus of intellectual laziness, the results are actually pretty thin. These studies, in which patients with an indication for a therapy (a beta-blocker in this case) are analyzed by whether or not they received it, are problematic. The fanciest statistics — in this case, they used propensity scores — can’t control for residual confounding. What drove the physicians to prescribe in some cases but not others? We can only guess.

This might be okay if there hadn’t been a randomized controlled trial (RCT) published in 2019 in The New England Journal of Medicine that found that beta-blockers increase the risk for severe COPD exacerbations. In EBM, the RCT trumps all. Ironically, this trial was designed to test whether beta-blockers reduce severe COPD exacerbations. Yes, we’d come full circle. There was enough biologic plausibility to support a positive effect, or so thought the study authors and the Department of Defense (DOD) — for reasons I can’t possibly guess, the DOD funded this RCT. My pharmacology professor must be rolling over in his tenure.

The RCT did leave beta-blockers some wiggle room. The authors purposely excluded anyone with a cardiovascular indication for a beta-blocker. The intent was to ensure beneficial effects were isolated to respiratory and not cardiovascular outcomes. Of course, the reason I’m writing and you’re reading this is that COPD and cardiovascular disease co-occur at a high rate. The RCT notwithstanding, we prescribe beta-blockers to patients with COPD because they have a cardiac indication, not to reduce acute COPD exacerbations. So, it’s possible there’d be a net beta-blocker benefit in patients with COPD and comorbid heart disease.

That’s where the JAMA Network Open study comes in, but as discussed, methodologic weaknesses preclude its being the final word. That said, I think it’s unlikely we’ll see a COPD with comorbid cardiac disease RCT performed to assess whether beta-blockers provide a net benefit, unless maybe the DOD wants to fund another one of these. In the meantime, I’m calling clinical equipoise and punting. Fortunately for me, I don’t have to prescribe beta-blockers. I suppose I could consider stopping them in my patient with severe COPD, the one I can’t keep out of the hospital, but I’m not convinced that would make much difference.
 

Dr. Holley is professor of medicine at Uniformed Services University in Bethesda, Maryland, and a pulmonary/sleep and critical care medicine physician at MedStar Washington Hospital Center in Washington, DC. He reported conflicts of interest with Metapharm, CHEST College, and WebMD.

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