Liam Davenport

Should a patient with high lipoprotein (a), or Lp(a), be started on low-dose aspirin?

This is the conundrum facing many physicians and patients, but even getting to that point will require more availability and coverage of tests and a greater appreciation of the risk associated with Lp(a), said cardiologists.
 

Lp(a): The Silent Risk

On Lp(a) Awareness Day, C. Michael Gibson, MD, MA, CEO of the Baim Institute for Clinical Research, Boston, Massachusetts, and PERFUSE took the opportunity to talk about his experiences with testing on X.

The professor of medicine at Harvard Medical School, also in Boston, said he was surprised to find that he had a very high calcium score, despite a low-density lipoprotein (LDL) cholesterol level of just 70 mg/dL. Eventually, he found out that he had a “very, very high Lp(a),” which was particularly concerning because his grandfather died of a heart attack at 45 years of age.

But how much risk does that represent?

A 2022 consensus statement from the European Atherosclerosis Society (EAS) highlighted that epidemiologic and genetic studies “strongly support a causal and continuous association between Lp(a) concentration and cardiovascular outcomes,” even at very low LDL cholesterol levels.

This is because Lp(a) has proinflammatory and proatherosclerotic properties, and high levels are associated with both micro- and macrocalcification of the aortic valve. Findings from a US registry study also suggest the threshold related to increased cardiovascular risk may differ for primary and secondary prevention populations (J Am Coll Cardiol. 2024 Mar 5;83[9]:873-886).

Lp(a) is, however, genetically determined, and there are no drugs available that directly lower levels, although some are on the horizon. In the meantime, the experts behind the consensus statement recommend that all adults be tested at least once in their lifetime.
 

Testing Cost and Availability

This recommendation has been translated into guidelines in “many, many” countries, said lead author Florian Kronenberg, MD, MAE, Institute of Genetic Epidemiology, Medical University of Innsbruck, Innsbruck, Austria, but “we are far away from reaching that goal.”

“We’ve got a real problem,” added Stephen Nicholls, MD, PhD, director of the Victorian Heart Institute and a professor of cardiology at Monash University, Melbourne, Australia, as there is “not a country in the world where there’s good access to Lp(a) testing.”

Dr. Kronenberg said that the consensus statement “created a kind of momentum” toward universal testing.

Ulrich Laufs, MD, PhD, professor and chair, Department of Cardiology, University Hospital Leipzig, Leipzig, Germany, agreed, saying that, overall, Lp(a) testing has “increased dramatically,” albeit from “extremely low levels.”

Dr. Kronenberg believes that “we have to be really patient.” He cited a lack of knowledge among physicians as one of the biggest barriers to greater uptake of testing.

“There is still no appreciation of the role of Lp(a),” agreed Alberico L. Catapano, MD, PhD, director of Cardiovascular Research and of the Lipoproteins and Atherosclerosis Laboratory of IRCCS Multimedica, Milan, Italy, and past president of the EAS.

“That’s why it’s not mentioned” to patients, he said. “What is really needed is to inform physician colleagues that Lp(a) is not only a risk factor but is the cause” of atherosclerotic cardiovascular disease (ASCVD).

Dr. Kronenberg said that the pressure for testing can often come from the patient themselves.

Physicians then question why the patient wants to be tested when there are no medications to treat it, he added. “We really tried very hard when we did the consensus paper to say that we should perform the test and give people advice on what to do.”

Dr. Catapano believes that another major obstacle is the cost of the test, which remains high “because very few people do it,” and there is some debate over which test to use.

Taken together, these issues have meant that “payers are really struggling with the idea of funding Lp(a),” said Dr. Nicholls, adding that “there seems to be this fixation on: ‘Well, if you can’t lower Lp(a), why measure it?’ ”

Rather than blame the payers, he says there is a need to educate about the science behind testing and underline that Lp(a) is an “important risk enhancer” for cardiovascular disease.

“Because if we’re going to make people pay out of pocket, then you’re creating a massive equity issue in that only those who can afford the test have it.”
 

High Lp(a) Now What?

But once the test has been performed, there then comes the question as to what to do about the result.

“Before we get anywhere near an agent that effectively lowers Lp(a) and get it into the clinic, there are lots of things that we can do today,” said Dr. Nicholls.

If someone has an intermediate or high background cardiovascular risk and they have got a high Lp(a) level, they “should be treated more intensively, as we know that high Lp(a) patients do better if their LDL cholesterol and their blood pressure is lower.”

For Dr. Catapano, this means having the “same mindset as you do with [a patient with] high blood pressure, high LDL cholesterol, and so on, because it’s exactly the same thing: It’s interacting with your other risk factors to increase your overall risk.”

Dr. Gibson agreed. Through a range of measures, including weight loss and statin therapy, he was able to reduce his overall cardiovascular risk, and his LDL cholesterol level dropped to just 20 mg/dL.
 

A Role for Aspirin?

However, one debate that has been rolling on in recent months is whether to start patients with elevated Lp(a) on low-dose aspirin.

It gained added momentum when Pablo Corral, MD, a lipidologist and a professor in the School of Medicine, Pharmacology Department, FASTA University, Mar del Plata, Buenos Aires, Argentina, highlighted the issue on X.

He pointed to a recent study, which showed that regular aspirin use was associated with a significantly lower rate of ASCVD mortality in adults without clinical ASCVD but who had elevated Lp(a).

Dr. Nicholls said that, when you “peel away the layers” of the current evidence, there is some suggestion that Lp(a)may be prothrombotic. “So in theory, perhaps aspirin might be maybe more intuitively useful there.”

He noted that the ASPREE primary prevention study found that low-dose aspirin in older adults resulted in a significantly higher risk for major hemorrhage over placebo and did not significantly reduce the risk for cardiovascular disease.

But an analysis he and his colleagues did suggest that aspirin may indeed benefit older individuals if they have elevated Lp(a) genotypes.
 

An Individual Decision

For Dr. Kronenberg and Dr. Laufs, there is currently a lack of appropriate data to make a recommendation either way, particularly for primary prevention.

They warned that the risk for thrombosis in patients with mildly elevated Lp(a) cannot be discounted, and in most cases either “the existing risk of bleeding exceeds the beneficial effects [of aspirin], or it’s not indicated,” said Dr. Laufs.

“When we make a recommendation, we should have evidence-based data,” Dr. Kronenberg said, but, at the moment, people “somehow put their finger in the air and see” which way the wind is blowing.

Dr. Catapano urged patients to talk to their physician, as even low-dose aspirin is “very potent” at inhibiting platelets.

Dr. Gibson agreed, saying that he is in two minds, as the potential benefit has to be weighed against the bleeding risk.

He personally takes low-dose aspirin because “I know I have a low bleeding risk,” but it is a decision “that has to be taken individually between a patient and their physician.”

Dr. Gibson, Dr. Kronenberg, Dr. Nicholls, and Dr. Catapano all reported conflicts of interest with numerous pharmaceutical companies and organizations.

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

Should a patient with high lipoprotein (a), or Lp(a), be started on low-dose aspirin?

This is the conundrum facing many physicians and patients, but even getting to that point will require more availability and coverage of tests and a greater appreciation of the risk associated with Lp(a), said cardiologists.
 

Lp(a): The Silent Risk

On Lp(a) Awareness Day, C. Michael Gibson, MD, MA, CEO of the Baim Institute for Clinical Research, Boston, Massachusetts, and PERFUSE took the opportunity to talk about his experiences with testing on X.

The professor of medicine at Harvard Medical School, also in Boston, said he was surprised to find that he had a very high calcium score, despite a low-density lipoprotein (LDL) cholesterol level of just 70 mg/dL. Eventually, he found out that he had a “very, very high Lp(a),” which was particularly concerning because his grandfather died of a heart attack at 45 years of age.

But how much risk does that represent?

A 2022 consensus statement from the European Atherosclerosis Society (EAS) highlighted that epidemiologic and genetic studies “strongly support a causal and continuous association between Lp(a) concentration and cardiovascular outcomes,” even at very low LDL cholesterol levels.

This is because Lp(a) has proinflammatory and proatherosclerotic properties, and high levels are associated with both micro- and macrocalcification of the aortic valve. Findings from a US registry study also suggest the threshold related to increased cardiovascular risk may differ for primary and secondary prevention populations (J Am Coll Cardiol. 2024 Mar 5;83[9]:873-886).

Lp(a) is, however, genetically determined, and there are no drugs available that directly lower levels, although some are on the horizon. In the meantime, the experts behind the consensus statement recommend that all adults be tested at least once in their lifetime.
 

Testing Cost and Availability

This recommendation has been translated into guidelines in “many, many” countries, said lead author Florian Kronenberg, MD, MAE, Institute of Genetic Epidemiology, Medical University of Innsbruck, Innsbruck, Austria, but “we are far away from reaching that goal.”

“We’ve got a real problem,” added Stephen Nicholls, MD, PhD, director of the Victorian Heart Institute and a professor of cardiology at Monash University, Melbourne, Australia, as there is “not a country in the world where there’s good access to Lp(a) testing.”

Dr. Kronenberg said that the consensus statement “created a kind of momentum” toward universal testing.

Ulrich Laufs, MD, PhD, professor and chair, Department of Cardiology, University Hospital Leipzig, Leipzig, Germany, agreed, saying that, overall, Lp(a) testing has “increased dramatically,” albeit from “extremely low levels.”

Dr. Kronenberg believes that “we have to be really patient.” He cited a lack of knowledge among physicians as one of the biggest barriers to greater uptake of testing.

“There is still no appreciation of the role of Lp(a),” agreed Alberico L. Catapano, MD, PhD, director of Cardiovascular Research and of the Lipoproteins and Atherosclerosis Laboratory of IRCCS Multimedica, Milan, Italy, and past president of the EAS.

“That’s why it’s not mentioned” to patients, he said. “What is really needed is to inform physician colleagues that Lp(a) is not only a risk factor but is the cause” of atherosclerotic cardiovascular disease (ASCVD).

Dr. Kronenberg said that the pressure for testing can often come from the patient themselves.

Physicians then question why the patient wants to be tested when there are no medications to treat it, he added. “We really tried very hard when we did the consensus paper to say that we should perform the test and give people advice on what to do.”

Dr. Catapano believes that another major obstacle is the cost of the test, which remains high “because very few people do it,” and there is some debate over which test to use.

Taken together, these issues have meant that “payers are really struggling with the idea of funding Lp(a),” said Dr. Nicholls, adding that “there seems to be this fixation on: ‘Well, if you can’t lower Lp(a), why measure it?’ ”

Rather than blame the payers, he says there is a need to educate about the science behind testing and underline that Lp(a) is an “important risk enhancer” for cardiovascular disease.

“Because if we’re going to make people pay out of pocket, then you’re creating a massive equity issue in that only those who can afford the test have it.”
 

High Lp(a) Now What?

But once the test has been performed, there then comes the question as to what to do about the result.

“Before we get anywhere near an agent that effectively lowers Lp(a) and get it into the clinic, there are lots of things that we can do today,” said Dr. Nicholls.

If someone has an intermediate or high background cardiovascular risk and they have got a high Lp(a) level, they “should be treated more intensively, as we know that high Lp(a) patients do better if their LDL cholesterol and their blood pressure is lower.”

For Dr. Catapano, this means having the “same mindset as you do with [a patient with] high blood pressure, high LDL cholesterol, and so on, because it’s exactly the same thing: It’s interacting with your other risk factors to increase your overall risk.”

Dr. Gibson agreed. Through a range of measures, including weight loss and statin therapy, he was able to reduce his overall cardiovascular risk, and his LDL cholesterol level dropped to just 20 mg/dL.
 

A Role for Aspirin?

However, one debate that has been rolling on in recent months is whether to start patients with elevated Lp(a) on low-dose aspirin.

It gained added momentum when Pablo Corral, MD, a lipidologist and a professor in the School of Medicine, Pharmacology Department, FASTA University, Mar del Plata, Buenos Aires, Argentina, highlighted the issue on X.

He pointed to a recent study, which showed that regular aspirin use was associated with a significantly lower rate of ASCVD mortality in adults without clinical ASCVD but who had elevated Lp(a).

Dr. Nicholls said that, when you “peel away the layers” of the current evidence, there is some suggestion that Lp(a)may be prothrombotic. “So in theory, perhaps aspirin might be maybe more intuitively useful there.”

He noted that the ASPREE primary prevention study found that low-dose aspirin in older adults resulted in a significantly higher risk for major hemorrhage over placebo and did not significantly reduce the risk for cardiovascular disease.

But an analysis he and his colleagues did suggest that aspirin may indeed benefit older individuals if they have elevated Lp(a) genotypes.
 

An Individual Decision

For Dr. Kronenberg and Dr. Laufs, there is currently a lack of appropriate data to make a recommendation either way, particularly for primary prevention.

They warned that the risk for thrombosis in patients with mildly elevated Lp(a) cannot be discounted, and in most cases either “the existing risk of bleeding exceeds the beneficial effects [of aspirin], or it’s not indicated,” said Dr. Laufs.

“When we make a recommendation, we should have evidence-based data,” Dr. Kronenberg said, but, at the moment, people “somehow put their finger in the air and see” which way the wind is blowing.

Dr. Catapano urged patients to talk to their physician, as even low-dose aspirin is “very potent” at inhibiting platelets.

Dr. Gibson agreed, saying that he is in two minds, as the potential benefit has to be weighed against the bleeding risk.

He personally takes low-dose aspirin because “I know I have a low bleeding risk,” but it is a decision “that has to be taken individually between a patient and their physician.”

Dr. Gibson, Dr. Kronenberg, Dr. Nicholls, and Dr. Catapano all reported conflicts of interest with numerous pharmaceutical companies and organizations.

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

Should a patient with high lipoprotein (a), or Lp(a), be started on low-dose aspirin?

This is the conundrum facing many physicians and patients, but even getting to that point will require more availability and coverage of tests and a greater appreciation of the risk associated with Lp(a), said cardiologists.
 

Lp(a): The Silent Risk

On Lp(a) Awareness Day, C. Michael Gibson, MD, MA, CEO of the Baim Institute for Clinical Research, Boston, Massachusetts, and PERFUSE took the opportunity to talk about his experiences with testing on X.

The professor of medicine at Harvard Medical School, also in Boston, said he was surprised to find that he had a very high calcium score, despite a low-density lipoprotein (LDL) cholesterol level of just 70 mg/dL. Eventually, he found out that he had a “very, very high Lp(a),” which was particularly concerning because his grandfather died of a heart attack at 45 years of age.

But how much risk does that represent?

A 2022 consensus statement from the European Atherosclerosis Society (EAS) highlighted that epidemiologic and genetic studies “strongly support a causal and continuous association between Lp(a) concentration and cardiovascular outcomes,” even at very low LDL cholesterol levels.

This is because Lp(a) has proinflammatory and proatherosclerotic properties, and high levels are associated with both micro- and macrocalcification of the aortic valve. Findings from a US registry study also suggest the threshold related to increased cardiovascular risk may differ for primary and secondary prevention populations (J Am Coll Cardiol. 2024 Mar 5;83[9]:873-886).

Lp(a) is, however, genetically determined, and there are no drugs available that directly lower levels, although some are on the horizon. In the meantime, the experts behind the consensus statement recommend that all adults be tested at least once in their lifetime.
 

Testing Cost and Availability

This recommendation has been translated into guidelines in “many, many” countries, said lead author Florian Kronenberg, MD, MAE, Institute of Genetic Epidemiology, Medical University of Innsbruck, Innsbruck, Austria, but “we are far away from reaching that goal.”

“We’ve got a real problem,” added Stephen Nicholls, MD, PhD, director of the Victorian Heart Institute and a professor of cardiology at Monash University, Melbourne, Australia, as there is “not a country in the world where there’s good access to Lp(a) testing.”

Dr. Kronenberg said that the consensus statement “created a kind of momentum” toward universal testing.

Ulrich Laufs, MD, PhD, professor and chair, Department of Cardiology, University Hospital Leipzig, Leipzig, Germany, agreed, saying that, overall, Lp(a) testing has “increased dramatically,” albeit from “extremely low levels.”

Dr. Kronenberg believes that “we have to be really patient.” He cited a lack of knowledge among physicians as one of the biggest barriers to greater uptake of testing.

“There is still no appreciation of the role of Lp(a),” agreed Alberico L. Catapano, MD, PhD, director of Cardiovascular Research and of the Lipoproteins and Atherosclerosis Laboratory of IRCCS Multimedica, Milan, Italy, and past president of the EAS.

“That’s why it’s not mentioned” to patients, he said. “What is really needed is to inform physician colleagues that Lp(a) is not only a risk factor but is the cause” of atherosclerotic cardiovascular disease (ASCVD).

Dr. Kronenberg said that the pressure for testing can often come from the patient themselves.

Physicians then question why the patient wants to be tested when there are no medications to treat it, he added. “We really tried very hard when we did the consensus paper to say that we should perform the test and give people advice on what to do.”

Dr. Catapano believes that another major obstacle is the cost of the test, which remains high “because very few people do it,” and there is some debate over which test to use.

Taken together, these issues have meant that “payers are really struggling with the idea of funding Lp(a),” said Dr. Nicholls, adding that “there seems to be this fixation on: ‘Well, if you can’t lower Lp(a), why measure it?’ ”

Rather than blame the payers, he says there is a need to educate about the science behind testing and underline that Lp(a) is an “important risk enhancer” for cardiovascular disease.

“Because if we’re going to make people pay out of pocket, then you’re creating a massive equity issue in that only those who can afford the test have it.”
 

High Lp(a) Now What?

But once the test has been performed, there then comes the question as to what to do about the result.

“Before we get anywhere near an agent that effectively lowers Lp(a) and get it into the clinic, there are lots of things that we can do today,” said Dr. Nicholls.

If someone has an intermediate or high background cardiovascular risk and they have got a high Lp(a) level, they “should be treated more intensively, as we know that high Lp(a) patients do better if their LDL cholesterol and their blood pressure is lower.”

For Dr. Catapano, this means having the “same mindset as you do with [a patient with] high blood pressure, high LDL cholesterol, and so on, because it’s exactly the same thing: It’s interacting with your other risk factors to increase your overall risk.”

Dr. Gibson agreed. Through a range of measures, including weight loss and statin therapy, he was able to reduce his overall cardiovascular risk, and his LDL cholesterol level dropped to just 20 mg/dL.
 

A Role for Aspirin?

However, one debate that has been rolling on in recent months is whether to start patients with elevated Lp(a) on low-dose aspirin.

It gained added momentum when Pablo Corral, MD, a lipidologist and a professor in the School of Medicine, Pharmacology Department, FASTA University, Mar del Plata, Buenos Aires, Argentina, highlighted the issue on X.

He pointed to a recent study, which showed that regular aspirin use was associated with a significantly lower rate of ASCVD mortality in adults without clinical ASCVD but who had elevated Lp(a).

Dr. Nicholls said that, when you “peel away the layers” of the current evidence, there is some suggestion that Lp(a)may be prothrombotic. “So in theory, perhaps aspirin might be maybe more intuitively useful there.”

He noted that the ASPREE primary prevention study found that low-dose aspirin in older adults resulted in a significantly higher risk for major hemorrhage over placebo and did not significantly reduce the risk for cardiovascular disease.

But an analysis he and his colleagues did suggest that aspirin may indeed benefit older individuals if they have elevated Lp(a) genotypes.
 

An Individual Decision

For Dr. Kronenberg and Dr. Laufs, there is currently a lack of appropriate data to make a recommendation either way, particularly for primary prevention.

They warned that the risk for thrombosis in patients with mildly elevated Lp(a) cannot be discounted, and in most cases either “the existing risk of bleeding exceeds the beneficial effects [of aspirin], or it’s not indicated,” said Dr. Laufs.

“When we make a recommendation, we should have evidence-based data,” Dr. Kronenberg said, but, at the moment, people “somehow put their finger in the air and see” which way the wind is blowing.

Dr. Catapano urged patients to talk to their physician, as even low-dose aspirin is “very potent” at inhibiting platelets.

Dr. Gibson agreed, saying that he is in two minds, as the potential benefit has to be weighed against the bleeding risk.

He personally takes low-dose aspirin because “I know I have a low bleeding risk,” but it is a decision “that has to be taken individually between a patient and their physician.”

Dr. Gibson, Dr. Kronenberg, Dr. Nicholls, and Dr. Catapano all reported conflicts of interest with numerous pharmaceutical companies and organizations.

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

LYON, FRANCE — The anti-obesity drug semaglutide is associated with significant reductions in the inflammatory marker high-sensitivity C-reactive protein (CRP), even in patients who do not lose substantial amounts of weight with the drug, according to data from the SELECT clinical trial.

The research, presented at the European Atherosclerosis Society 2024, involved over 17,600 patients with overweight or obesity and had established cardiovascular disease but not diabetes.

Those given semaglutide experienced a 38% reduction in high-sensitivity CRP levels compared with placebo regardless of baseline body mass index, statin use, cholesterol levels, and other measures.

“Weight loss was associated with greater high-sensitivity CRP reduction in both treatment groups,” said study presenter Jorge Plutzky, MD, director of Preventive Cardiology at Brigham and Women’s Hospital, Boston, but “with increased high-sensitivity CRP reductions in those receiving semaglutide.”

The drug also “significantly reduced high-sensitivity CRP early,” he said, “prior to major weight loss and in those who did not lose significant amounts of weight.” The reductions reached approximately 12% at 4 weeks and around 20% at 8 weeks, when the weight loss “was still quite modest,” at 2% and 3% of body weight, respectively. Even among patients who achieved weight loss of less than 2% body weight, semaglutide was associated with a reduction in high-sensitivity CRP levels.

In the SELECT trial, semaglutide also resulted in a consistent reduction of around 20% vs placebo in major adverse cardiovascular events such as cardiovascular mortality, nonfatal myocardial infarction, or nonfatal stroke.

But Naveed Sattar, MD, PhD, professor of cardiometabolic medicine at the University of Glasgow, Scotland, said in an interview that body weight “is probably the major driver” of CRP levels in the population, accounting for between 20% and 30% of the variation.

Dr. Sattar, who was not involved in the study, said that because drugs like semaglutide lower weight but also have anti-inflammatory effects, the question becomes: “Could the anti-inflammatory effects be part of the mechanisms by which these drugs affect the risk of major adverse cardiovascular events?”
 

Reducing Cardiovascular Events

The current analysis, however, cannot answer the question, he said. “All it tells us is about associations.”

“What we do know is semaglutide, predominantly by lowering weight, is lowering CRP levels and equally, we know that when you lose weight, you improve blood pressure, you improve lipids, and you reduce the risk of diabetes,” he said.

Dr. Sattar also took issue with the researchers’ conclusion that the high-sensitivity CRP reductions seen in SELECT occurred prior to major weight loss because the “pattern of CRP reduction and weight reduction is almost identical.”

Dr. Sattar also pointed out in a recent editorial that the drug appears to have a direct effect on blood vessels and the heart, which may lead to improvements in systemic inflammation. Consequently, he said, any assertion that semaglutide is genuinely anti-inflammatory is, at this stage, “speculation.”

Dr. Plutzky said that “systemic, chronic inflammation is implicated as a potential mechanism and therapeutic target in atherosclerosis and major adverse cardiovascular events, as well as obesity,” and high-sensitivity CRP levels are an “established biomarker of inflammation and have been shown to predict cardiovascular risk.”

However, the relationship between high-sensitivity CRP, responses to glucagon-like peptide 1 receptor agonists like semaglutide, and cardiovascular outcomes in obesity “remains incompletely understood,” said Dr. Plutzky.
 

A version of this article appeared on Medscape.com.

LYON, FRANCE — The anti-obesity drug semaglutide is associated with significant reductions in the inflammatory marker high-sensitivity C-reactive protein (CRP), even in patients who do not lose substantial amounts of weight with the drug, according to data from the SELECT clinical trial.

The research, presented at the European Atherosclerosis Society 2024, involved over 17,600 patients with overweight or obesity and had established cardiovascular disease but not diabetes.

Those given semaglutide experienced a 38% reduction in high-sensitivity CRP levels compared with placebo regardless of baseline body mass index, statin use, cholesterol levels, and other measures.

“Weight loss was associated with greater high-sensitivity CRP reduction in both treatment groups,” said study presenter Jorge Plutzky, MD, director of Preventive Cardiology at Brigham and Women’s Hospital, Boston, but “with increased high-sensitivity CRP reductions in those receiving semaglutide.”

The drug also “significantly reduced high-sensitivity CRP early,” he said, “prior to major weight loss and in those who did not lose significant amounts of weight.” The reductions reached approximately 12% at 4 weeks and around 20% at 8 weeks, when the weight loss “was still quite modest,” at 2% and 3% of body weight, respectively. Even among patients who achieved weight loss of less than 2% body weight, semaglutide was associated with a reduction in high-sensitivity CRP levels.

In the SELECT trial, semaglutide also resulted in a consistent reduction of around 20% vs placebo in major adverse cardiovascular events such as cardiovascular mortality, nonfatal myocardial infarction, or nonfatal stroke.

But Naveed Sattar, MD, PhD, professor of cardiometabolic medicine at the University of Glasgow, Scotland, said in an interview that body weight “is probably the major driver” of CRP levels in the population, accounting for between 20% and 30% of the variation.

Dr. Sattar, who was not involved in the study, said that because drugs like semaglutide lower weight but also have anti-inflammatory effects, the question becomes: “Could the anti-inflammatory effects be part of the mechanisms by which these drugs affect the risk of major adverse cardiovascular events?”
 

Reducing Cardiovascular Events

The current analysis, however, cannot answer the question, he said. “All it tells us is about associations.”

“What we do know is semaglutide, predominantly by lowering weight, is lowering CRP levels and equally, we know that when you lose weight, you improve blood pressure, you improve lipids, and you reduce the risk of diabetes,” he said.

Dr. Sattar also took issue with the researchers’ conclusion that the high-sensitivity CRP reductions seen in SELECT occurred prior to major weight loss because the “pattern of CRP reduction and weight reduction is almost identical.”

Dr. Sattar also pointed out in a recent editorial that the drug appears to have a direct effect on blood vessels and the heart, which may lead to improvements in systemic inflammation. Consequently, he said, any assertion that semaglutide is genuinely anti-inflammatory is, at this stage, “speculation.”

Dr. Plutzky said that “systemic, chronic inflammation is implicated as a potential mechanism and therapeutic target in atherosclerosis and major adverse cardiovascular events, as well as obesity,” and high-sensitivity CRP levels are an “established biomarker of inflammation and have been shown to predict cardiovascular risk.”

However, the relationship between high-sensitivity CRP, responses to glucagon-like peptide 1 receptor agonists like semaglutide, and cardiovascular outcomes in obesity “remains incompletely understood,” said Dr. Plutzky.
 

A version of this article appeared on Medscape.com.

LYON, FRANCE — The anti-obesity drug semaglutide is associated with significant reductions in the inflammatory marker high-sensitivity C-reactive protein (CRP), even in patients who do not lose substantial amounts of weight with the drug, according to data from the SELECT clinical trial.

The research, presented at the European Atherosclerosis Society 2024, involved over 17,600 patients with overweight or obesity and had established cardiovascular disease but not diabetes.

Those given semaglutide experienced a 38% reduction in high-sensitivity CRP levels compared with placebo regardless of baseline body mass index, statin use, cholesterol levels, and other measures.

“Weight loss was associated with greater high-sensitivity CRP reduction in both treatment groups,” said study presenter Jorge Plutzky, MD, director of Preventive Cardiology at Brigham and Women’s Hospital, Boston, but “with increased high-sensitivity CRP reductions in those receiving semaglutide.”

The drug also “significantly reduced high-sensitivity CRP early,” he said, “prior to major weight loss and in those who did not lose significant amounts of weight.” The reductions reached approximately 12% at 4 weeks and around 20% at 8 weeks, when the weight loss “was still quite modest,” at 2% and 3% of body weight, respectively. Even among patients who achieved weight loss of less than 2% body weight, semaglutide was associated with a reduction in high-sensitivity CRP levels.

In the SELECT trial, semaglutide also resulted in a consistent reduction of around 20% vs placebo in major adverse cardiovascular events such as cardiovascular mortality, nonfatal myocardial infarction, or nonfatal stroke.

But Naveed Sattar, MD, PhD, professor of cardiometabolic medicine at the University of Glasgow, Scotland, said in an interview that body weight “is probably the major driver” of CRP levels in the population, accounting for between 20% and 30% of the variation.

Dr. Sattar, who was not involved in the study, said that because drugs like semaglutide lower weight but also have anti-inflammatory effects, the question becomes: “Could the anti-inflammatory effects be part of the mechanisms by which these drugs affect the risk of major adverse cardiovascular events?”
 

Reducing Cardiovascular Events

The current analysis, however, cannot answer the question, he said. “All it tells us is about associations.”

“What we do know is semaglutide, predominantly by lowering weight, is lowering CRP levels and equally, we know that when you lose weight, you improve blood pressure, you improve lipids, and you reduce the risk of diabetes,” he said.

Dr. Sattar also took issue with the researchers’ conclusion that the high-sensitivity CRP reductions seen in SELECT occurred prior to major weight loss because the “pattern of CRP reduction and weight reduction is almost identical.”

Dr. Sattar also pointed out in a recent editorial that the drug appears to have a direct effect on blood vessels and the heart, which may lead to improvements in systemic inflammation. Consequently, he said, any assertion that semaglutide is genuinely anti-inflammatory is, at this stage, “speculation.”

Dr. Plutzky said that “systemic, chronic inflammation is implicated as a potential mechanism and therapeutic target in atherosclerosis and major adverse cardiovascular events, as well as obesity,” and high-sensitivity CRP levels are an “established biomarker of inflammation and have been shown to predict cardiovascular risk.”

However, the relationship between high-sensitivity CRP, responses to glucagon-like peptide 1 receptor agonists like semaglutide, and cardiovascular outcomes in obesity “remains incompletely understood,” said Dr. Plutzky.
 

A version of this article appeared on Medscape.com.

LYON, France – Lerodalcibep, a novel, third-generation anti-proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, helps high-risk patients already receiving maximally tolerated statins to achieve guideline lipid targets, reported investigators.

In the randomized, placebo-controlled LIBerate-CVD trial of more than 900 patients, lerodalcibep led to reductions from baseline in low-density lipoprotein (LDL) cholesterol levels of more than 60%.

“We believe that lerodalcibep offers a novel, effective alternative to current PCSK9 inhibitors for patients with cardiovascular disease or at very high risk for cardiovascular disease,” said Evan Stein, MD, PhD, chief scientific officer and cofounder of LIB Therapeutics in Chicago, who presented the findings at the European Atherosclerosis Society (EAS) 2024.

Moreover, it leads to “substantial additional LDL cholesterol reductions on top of existing oral agents” and allows more than 90% of patients to achieve the latest European Society of Cardiology (ESC) guideline targets, he said.

Lerodalcibep has “tolerability and safety similar to placebo,” Dr. Stein said, and requires only “a small monthly injection, which takes about 12 seconds.”

“The drug doesn’t require refrigeration” and is “stable, so far, over 9 months,” he reported.

The latest data “confirm the efficacy of lerodalcibep,” said Giuseppe Danilo Norata, PhD, from the Department of Pharmacological and Biomolecular Sciences at the University of Milan, Milan, Italy, who was not involved in the study.

The LDL cholesterol reduction in this phase 3 trial is “in line with what was observed in LIBerate-FH,” and the high proportion of patients achieving their LDL cholesterol target is “impressive,” he added.
 

Effective and Well Tolerated

The safety results are “suggestive of a drug that is well tolerated, with injection-site reactions being the only remarkable adverse event increased in the treatment group,” Dr. Norata reported.

Only a “limited number” of patients developed neutralizing antidrug antibodies, which did not affect the efficacy of lerodalcibep. However, “given that the therapy is expected to be administered for years,” a longer analysis is needed to exclude the concern that a small percentage of neutralizing antidrug antibodies could reduce the efficacy, he said.

If approved, lerodalcibep could end up as a first-line option in the treatment pathway for high-risk cardiovascular disease because the efficacy “is similar to that of other injectable PCSK9 inhibitors,” he said, adding that its position in the market will “largely depend on the price.”

As the mechanism of action is similar to that of other monoclonal antibodies, “there is no pharmacological rationale to use it after another PSCK9 inhibitor,” he explained.

Lerodalcibep is a small recombinant fusion protein that combines a PCSK9-binding domain with human serum albumin.

The binding domain blocks the interaction between PCSK9 and the LDL cholesterol receptor, and the albumin linkage increases the half-life to 12-15 days, allowing low-volume injections to be given every 4 weeks.

A prior phase 2 study suggested that lerodalcibep substantially decreases LDL cholesterol levels in patients already taking maximally tolerated statins. The 300-mg dose was associated with an average reduction from baseline in LDL cholesterol levels of 77% over 12 weeks, whereas free PCSK9 levels decreased by 88%.

The current phase 3 study enrolled individuals at 65 centers in 100 countries who had or were at a very high risk for cardiovascular disease and who had an LDL cholesterol level of ≥ 1.8 mmol/L despite being on maximally tolerated statins.

Study participants were randomized in a 2:1 ratio to receive monthly subcutaneous lerodalcibep (n = 614) or placebo (n = 308) for 52 weeks and were assessed for the co-primary endpoints of the percentage change in LDL cholesterol levels from baseline to week 52 and the mean of levels at weeks 50 and 52.

The mean age was similar in the lerodalcibep and placebo groups (63.3 vs 64.5 years), as were the proportion of female (30% vs 30%) and White (80% vs 79%) participants.

The vast majority of participants in the lerodalcibep and placebo groups had a documented cardiovascular event (85.3% vs 86.4%) and were receiving secondary prevention, and 87% and 82%, respectively, were receiving a statin (any dose).

In a modified intention-to-treat analysis, the mean placebo-adjusted reduction in LDL cholesterol levels from baseline with lerodalcibep was 62% at week 52 (P < .0001), and the mean of levels at weeks 50 and 52 was 69.4% (P < .0001).

Similar results were seen in a per protocol analysis and an intention-to-treat analysis with imputation, which is a US Food and Drug Administration measure introduced in 2021 that assumes patients who discontinue the study treatment have an outcome similar to that in the placebo patients.

Moreover, 98.2% of patients in the lerodalcibep group achieved the ESC and European Atherosclerosis Society recommended reduction in LDL cholesterol levels of ≥ 50%, whereas only 8.8% in the placebo group did.
 

Hitting the LDL Cholesterol Target

More patients in the lerodalcibep group than in the placebo group achieved the LDL cholesterol target of < 1.4 mmol/L (95.3% vs 18.5%), and more patients in the lerodalcibep group achieved both that target and the ≥ 50% target (94.5% and 6.8%).

Lerodalcibep was also associated with significant reductions from baseline in levels of non–high-density lipoprotein (HDL) cholesterol, apolipoprotein B, very LDL cholesterol, and triglycerides, as well as an increase in HDL cholesterol levels (P < .0001 for all).

In terms of safety, lerodalcibep was associated with an adverse event rate leading to withdrawal similar to that seen with placebo (4.2% vs 3.6%), and 15.9% and 14.8% of patients, respectively, experienced at least one serious adverse event.

In-stent restenosis occurred more often in the lerodalcibep group than in the placebo group (5.4% vs 2.0%).

The study drug was associated with low levels of transient and sporadic antidrug antibodies and a low rate of neutralizing antidrug antibodies (0.9%), which were not associated with restenosis, a reduction in free PCSK9 levels, or the ability of lerodalcibep to lower LDL cholesterol levels.

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

LYON, France – Lerodalcibep, a novel, third-generation anti-proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, helps high-risk patients already receiving maximally tolerated statins to achieve guideline lipid targets, reported investigators.

In the randomized, placebo-controlled LIBerate-CVD trial of more than 900 patients, lerodalcibep led to reductions from baseline in low-density lipoprotein (LDL) cholesterol levels of more than 60%.

“We believe that lerodalcibep offers a novel, effective alternative to current PCSK9 inhibitors for patients with cardiovascular disease or at very high risk for cardiovascular disease,” said Evan Stein, MD, PhD, chief scientific officer and cofounder of LIB Therapeutics in Chicago, who presented the findings at the European Atherosclerosis Society (EAS) 2024.

Moreover, it leads to “substantial additional LDL cholesterol reductions on top of existing oral agents” and allows more than 90% of patients to achieve the latest European Society of Cardiology (ESC) guideline targets, he said.

Lerodalcibep has “tolerability and safety similar to placebo,” Dr. Stein said, and requires only “a small monthly injection, which takes about 12 seconds.”

“The drug doesn’t require refrigeration” and is “stable, so far, over 9 months,” he reported.

The latest data “confirm the efficacy of lerodalcibep,” said Giuseppe Danilo Norata, PhD, from the Department of Pharmacological and Biomolecular Sciences at the University of Milan, Milan, Italy, who was not involved in the study.

The LDL cholesterol reduction in this phase 3 trial is “in line with what was observed in LIBerate-FH,” and the high proportion of patients achieving their LDL cholesterol target is “impressive,” he added.
 

Effective and Well Tolerated

The safety results are “suggestive of a drug that is well tolerated, with injection-site reactions being the only remarkable adverse event increased in the treatment group,” Dr. Norata reported.

Only a “limited number” of patients developed neutralizing antidrug antibodies, which did not affect the efficacy of lerodalcibep. However, “given that the therapy is expected to be administered for years,” a longer analysis is needed to exclude the concern that a small percentage of neutralizing antidrug antibodies could reduce the efficacy, he said.

If approved, lerodalcibep could end up as a first-line option in the treatment pathway for high-risk cardiovascular disease because the efficacy “is similar to that of other injectable PCSK9 inhibitors,” he said, adding that its position in the market will “largely depend on the price.”

As the mechanism of action is similar to that of other monoclonal antibodies, “there is no pharmacological rationale to use it after another PSCK9 inhibitor,” he explained.

Lerodalcibep is a small recombinant fusion protein that combines a PCSK9-binding domain with human serum albumin.

The binding domain blocks the interaction between PCSK9 and the LDL cholesterol receptor, and the albumin linkage increases the half-life to 12-15 days, allowing low-volume injections to be given every 4 weeks.

A prior phase 2 study suggested that lerodalcibep substantially decreases LDL cholesterol levels in patients already taking maximally tolerated statins. The 300-mg dose was associated with an average reduction from baseline in LDL cholesterol levels of 77% over 12 weeks, whereas free PCSK9 levels decreased by 88%.

The current phase 3 study enrolled individuals at 65 centers in 100 countries who had or were at a very high risk for cardiovascular disease and who had an LDL cholesterol level of ≥ 1.8 mmol/L despite being on maximally tolerated statins.

Study participants were randomized in a 2:1 ratio to receive monthly subcutaneous lerodalcibep (n = 614) or placebo (n = 308) for 52 weeks and were assessed for the co-primary endpoints of the percentage change in LDL cholesterol levels from baseline to week 52 and the mean of levels at weeks 50 and 52.

The mean age was similar in the lerodalcibep and placebo groups (63.3 vs 64.5 years), as were the proportion of female (30% vs 30%) and White (80% vs 79%) participants.

The vast majority of participants in the lerodalcibep and placebo groups had a documented cardiovascular event (85.3% vs 86.4%) and were receiving secondary prevention, and 87% and 82%, respectively, were receiving a statin (any dose).

In a modified intention-to-treat analysis, the mean placebo-adjusted reduction in LDL cholesterol levels from baseline with lerodalcibep was 62% at week 52 (P < .0001), and the mean of levels at weeks 50 and 52 was 69.4% (P < .0001).

Similar results were seen in a per protocol analysis and an intention-to-treat analysis with imputation, which is a US Food and Drug Administration measure introduced in 2021 that assumes patients who discontinue the study treatment have an outcome similar to that in the placebo patients.

Moreover, 98.2% of patients in the lerodalcibep group achieved the ESC and European Atherosclerosis Society recommended reduction in LDL cholesterol levels of ≥ 50%, whereas only 8.8% in the placebo group did.
 

Hitting the LDL Cholesterol Target

More patients in the lerodalcibep group than in the placebo group achieved the LDL cholesterol target of < 1.4 mmol/L (95.3% vs 18.5%), and more patients in the lerodalcibep group achieved both that target and the ≥ 50% target (94.5% and 6.8%).

Lerodalcibep was also associated with significant reductions from baseline in levels of non–high-density lipoprotein (HDL) cholesterol, apolipoprotein B, very LDL cholesterol, and triglycerides, as well as an increase in HDL cholesterol levels (P < .0001 for all).

In terms of safety, lerodalcibep was associated with an adverse event rate leading to withdrawal similar to that seen with placebo (4.2% vs 3.6%), and 15.9% and 14.8% of patients, respectively, experienced at least one serious adverse event.

In-stent restenosis occurred more often in the lerodalcibep group than in the placebo group (5.4% vs 2.0%).

The study drug was associated with low levels of transient and sporadic antidrug antibodies and a low rate of neutralizing antidrug antibodies (0.9%), which were not associated with restenosis, a reduction in free PCSK9 levels, or the ability of lerodalcibep to lower LDL cholesterol levels.

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

LYON, France – Lerodalcibep, a novel, third-generation anti-proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, helps high-risk patients already receiving maximally tolerated statins to achieve guideline lipid targets, reported investigators.

In the randomized, placebo-controlled LIBerate-CVD trial of more than 900 patients, lerodalcibep led to reductions from baseline in low-density lipoprotein (LDL) cholesterol levels of more than 60%.

“We believe that lerodalcibep offers a novel, effective alternative to current PCSK9 inhibitors for patients with cardiovascular disease or at very high risk for cardiovascular disease,” said Evan Stein, MD, PhD, chief scientific officer and cofounder of LIB Therapeutics in Chicago, who presented the findings at the European Atherosclerosis Society (EAS) 2024.

Moreover, it leads to “substantial additional LDL cholesterol reductions on top of existing oral agents” and allows more than 90% of patients to achieve the latest European Society of Cardiology (ESC) guideline targets, he said.

Lerodalcibep has “tolerability and safety similar to placebo,” Dr. Stein said, and requires only “a small monthly injection, which takes about 12 seconds.”

“The drug doesn’t require refrigeration” and is “stable, so far, over 9 months,” he reported.

The latest data “confirm the efficacy of lerodalcibep,” said Giuseppe Danilo Norata, PhD, from the Department of Pharmacological and Biomolecular Sciences at the University of Milan, Milan, Italy, who was not involved in the study.

The LDL cholesterol reduction in this phase 3 trial is “in line with what was observed in LIBerate-FH,” and the high proportion of patients achieving their LDL cholesterol target is “impressive,” he added.
 

Effective and Well Tolerated

The safety results are “suggestive of a drug that is well tolerated, with injection-site reactions being the only remarkable adverse event increased in the treatment group,” Dr. Norata reported.

Only a “limited number” of patients developed neutralizing antidrug antibodies, which did not affect the efficacy of lerodalcibep. However, “given that the therapy is expected to be administered for years,” a longer analysis is needed to exclude the concern that a small percentage of neutralizing antidrug antibodies could reduce the efficacy, he said.

If approved, lerodalcibep could end up as a first-line option in the treatment pathway for high-risk cardiovascular disease because the efficacy “is similar to that of other injectable PCSK9 inhibitors,” he said, adding that its position in the market will “largely depend on the price.”

As the mechanism of action is similar to that of other monoclonal antibodies, “there is no pharmacological rationale to use it after another PSCK9 inhibitor,” he explained.

Lerodalcibep is a small recombinant fusion protein that combines a PCSK9-binding domain with human serum albumin.

The binding domain blocks the interaction between PCSK9 and the LDL cholesterol receptor, and the albumin linkage increases the half-life to 12-15 days, allowing low-volume injections to be given every 4 weeks.

A prior phase 2 study suggested that lerodalcibep substantially decreases LDL cholesterol levels in patients already taking maximally tolerated statins. The 300-mg dose was associated with an average reduction from baseline in LDL cholesterol levels of 77% over 12 weeks, whereas free PCSK9 levels decreased by 88%.

The current phase 3 study enrolled individuals at 65 centers in 100 countries who had or were at a very high risk for cardiovascular disease and who had an LDL cholesterol level of ≥ 1.8 mmol/L despite being on maximally tolerated statins.

Study participants were randomized in a 2:1 ratio to receive monthly subcutaneous lerodalcibep (n = 614) or placebo (n = 308) for 52 weeks and were assessed for the co-primary endpoints of the percentage change in LDL cholesterol levels from baseline to week 52 and the mean of levels at weeks 50 and 52.

The mean age was similar in the lerodalcibep and placebo groups (63.3 vs 64.5 years), as were the proportion of female (30% vs 30%) and White (80% vs 79%) participants.

The vast majority of participants in the lerodalcibep and placebo groups had a documented cardiovascular event (85.3% vs 86.4%) and were receiving secondary prevention, and 87% and 82%, respectively, were receiving a statin (any dose).

In a modified intention-to-treat analysis, the mean placebo-adjusted reduction in LDL cholesterol levels from baseline with lerodalcibep was 62% at week 52 (P < .0001), and the mean of levels at weeks 50 and 52 was 69.4% (P < .0001).

Similar results were seen in a per protocol analysis and an intention-to-treat analysis with imputation, which is a US Food and Drug Administration measure introduced in 2021 that assumes patients who discontinue the study treatment have an outcome similar to that in the placebo patients.

Moreover, 98.2% of patients in the lerodalcibep group achieved the ESC and European Atherosclerosis Society recommended reduction in LDL cholesterol levels of ≥ 50%, whereas only 8.8% in the placebo group did.
 

Hitting the LDL Cholesterol Target

More patients in the lerodalcibep group than in the placebo group achieved the LDL cholesterol target of < 1.4 mmol/L (95.3% vs 18.5%), and more patients in the lerodalcibep group achieved both that target and the ≥ 50% target (94.5% and 6.8%).

Lerodalcibep was also associated with significant reductions from baseline in levels of non–high-density lipoprotein (HDL) cholesterol, apolipoprotein B, very LDL cholesterol, and triglycerides, as well as an increase in HDL cholesterol levels (P < .0001 for all).

In terms of safety, lerodalcibep was associated with an adverse event rate leading to withdrawal similar to that seen with placebo (4.2% vs 3.6%), and 15.9% and 14.8% of patients, respectively, experienced at least one serious adverse event.

In-stent restenosis occurred more often in the lerodalcibep group than in the placebo group (5.4% vs 2.0%).

The study drug was associated with low levels of transient and sporadic antidrug antibodies and a low rate of neutralizing antidrug antibodies (0.9%), which were not associated with restenosis, a reduction in free PCSK9 levels, or the ability of lerodalcibep to lower LDL cholesterol levels.

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

A central aim of prostate cancer treatment is to prolong survival, but trials often overlook another key goal: Improving — or at least maintaining — quality of life (QoL).

The recent American Society of Clinical Oncology (ASCO) 2024 annual meeting dedicated a session to QoL outcomes in men with prostate cancer.

The trials explored the effects of treatment suspension or intensification on health-related QoL as well as interventions to manage side effects in different patient populations.

The first presentation focused on a post hoc analysis of the phase 3 EMBARK trial, which looked at the effect of suspending treatment on health-related QoL in men with nonmetastatic disease at a high risk for biochemical recurrence.

Earlier findings from the trial, presented at ESMO in 2023, showed enzalutamide alone or in combination with androgen deprivation therapy (ADT) was associated with a significant improvement in metastasis-free survival vs placebo plus leuprolide.

The initial trial randomized 1068 patients at a high risk for biochemical recurrence to these three treatment groups and suspended therapy at week 37 if prostate-specific antigen (PSA) levels fell below 0.2 ng/mL. Patients, however, were not randomized into the treatment suspension groups. Treatment resumed if PSA levels rose to ≥ 2.0 ng/mL in patients who had undergone radical prostatectomy or ≥ 5.0 ng/mL in those who had not had surgery.

The post hoc analysis, which assessed patient-reported QoL outcomes following treatment suspension at baseline and every 12 weeks until progression, found no meaningful changes in the worst pain in the past 24 hours, as measured by the Brief Pain Inventory–Short Form.

Patients also reported no meaningful changes in total and physical well-being scores on the Functional Assessment of Cancer Therapy–Prostate (FACT-P) and on the European Quality of Life Five-Dimensions (EuroQol-5D) visual analog scale score, as well as no meaningful changes in sexual activity and urinary and bowel symptoms, based on scores from the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–Prostate 25 (QLQ-PR25).

Hormone treatment-related symptoms on the QLQ-PR25, however, “quickly improved but eventually began to worsen after week 97,” explained lead author Stephen J. Freedland, MD, from Cedars-Sinai Medical Center, Los Angeles, California, who presented the new findings at ASCO.

Dr. Freedland concluded that the EMBARK results show that enzalutamide, with or without ADT, improves metastasis-free survival vs leuprolide alone, without affecting global health-related QoL during treatment or after treatment suspension.

However, Channing J. Paller, MD, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Medicine, Baltimore, Maryland, who was not involved in the research, pointed out that “patient selection is key” when choosing therapies, given that ADT has distinct adverse effects. Comorbidities and adverse effects “must be taken into consideration to help the doctor and patient make more personalized treatment choices.”
 

Treatment Intensification and QoL

Another presentation explored health-related QoL outcomes from the phase 3 PRESTO trial.

The study examined ADT intensification in 504 patients who had high-risk biochemically relapsed nonmetastatic hormone-sensitive prostate cancer and a PSA doubling time of 9 months or less. Patients were randomized to ADT monotherapy with degarelix or leuprolide, ADT plus apalutamide, or ADT plus apalutamide, abiraterone acetate, and prednisone.

In previous data from PRESTO, the combination therapy groups both had significantly longer median PSA progression-free survival than the ADT monotherapy arm.

The latest data looked at the health-related QoL outcomes in the PRESTO population, measured using the Expanded Prostate Cancer Index Composite, the PROMIS Fatigue tool, the Hot Flash Related Daily Interference Scale, and the EuroQol-5D.

Ronald C. Chen, MD, MPH, of the University of Kansas Medical Center, Kansas City, who presented the new findings at ASCO, reported that ADT plus apalutamide improved PSA progression-free survival over ADT alone and did not meaningfully increase common treatment-related symptoms, such as hormonal symptoms, sexual dysfunction, hot flash interference, and fatigue.

However, treatment intensification with triple androgen regimen did not lead to further improvements in PSA progression-free survival but did increase the rate of serious adverse events, the time to testosterone recover, and increased hot flash interference.

PRESTO as well as EMBARK “provide a strong rationale for intensification of androgen blockade in men with high-risk biochemical recurrence after completing primary local therapy” and could even “reduce the need for subsequent treatment,” concluded Dr. Chen.
 

CBT for Managing ADT Side Effects

Up to 80% of men receiving ADT to treat prostate cancer experience night sweats and hot flashes, which are associated with sleep disturbance, anxiety, low mood, and cognitive impairments.

A third trial presented during the session looked at the impact of cognitive-behavioral therapy (CBT) on these side effects of ADT treatment.

Initial findings from the MANCAN study found that CBT delivered by a psychologist reduced the impact of hot flashes and night sweats at 6 weeks.

The MANCAN2 study assessed QoL at 6 months among 162 patients with localized or advanced prostate cancer who underwent at least 6 months of continuous ADT and who experienced more severe hot flashes and night sweats, defined as a score of ≥ 2 on the hot flashes and night sweats problem rating scale.

Study participants were randomized to CBT plus treatment as usual, or treatment as usual alone, with the intervention consisting of two CBT group sessions 4 weeks apart. Between CBT sessions, patients could refer to a booklet and CD, alongside exercises and CBT strategies.

MANCAN2 confirmed that CBT was associated with a significantly greater reduction in hot flash and night sweat scores over standard care alone at 6 weeks. Patients receiving CBT also reported better QoL, sleep, and functional status but those differences did not reach statistical significance.

By 6 months, those in the CBT group still reported better outcomes in each category, but no differences were statistically significant at this time point. Overall, however, 14% of treatment as usual alone patients discontinued ADT at 6 months vs none in the CBT arm.

“Further research is therefore needed to determine whether or not you can make this effect more durable” and to look at “the potential for CBT to support treatment compliance,” said study presenter Simon J. Crabb, PhD, MBBS, from the University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, England.
 

QoL With Radioligand Crossover

Finally, the phase 3 PSMAfore study compared ¹⁷⁷Lu-PSMA-617 with abiraterone or enzalutamide in 468 taxane-naive patients with metastatic castration-resistant prostate cancer who had progressed on a previous androgen receptor pathway inhibitor.

In earlier analyses, Karim Fizazi, MD, PhD, Institut Gustave Roussy, Université Paris-Saclay, Paris, France, reported that ¹⁷⁷Lu-PSMA-617 improved radiographic progression-free survival by 59% over androgen receptor pathway inhibitor therapy but did not lead to significant differences in overall survival.

In a new interim analysis, Dr. Fizazi and colleagues explored outcomes in patients eligible to cross over to ¹⁷⁷Lu-PSMA-617 following androgen receptor pathway inhibitor therapy. Assessments of health-related QoL revealed that ¹⁷⁷Lu-PSMA-617 led to about a 40% improvement in scores on two QoL tools — 41% with FACT-P and 39% with EuroQol-5D.

On subscales of FACT-P, Dr. Fizazi reported that ¹⁷⁷Lu-PSMA-617 was also associated with a significantly longer time to worsening in physical, functional, and emotional well-being over standard therapy. A pain inventory score indicated that ¹⁷⁷Lu-PSMA-617 led to a 31% improvement in the time to worsening pain intensity, as well as a 33% increase in the time to worsening pain interference.

With the treatment having a “favorable safety profile,” Dr. Fizazi said the results suggest ¹⁷⁷Lu-PSMA-617 is a “treatment option” for patients with metastatic castration-resistant prostate cancer who have undergone androgen receptor pathway inhibitor treatment.

MANCAN2 was funded by the UK National Institute for Health and Care Research. EMBARK was funded by Astellas Pharma and Pfizer, the codevelopers of enzalutamide. PRESTO was funded by Alliance Foundation Trials and Johnson & Johnson. PSMAfore was funded by Novartis. Dr. Freedland declared relationships with Pfizer and Astellas Pharma, among others. Paller declared relationships with AstraZeneca, Dendreon, Exelixis, Janssen Oncology, Omnitura, Lilly, and Bayer. Dr. Chen declared relationships with Astellas Pharma, Pfizer, and others. Dr. Crabb declared relationships with AstraZeneca, Bristol-Myers Squibb, Ipsen, Merck, Amgen, Amphista Therapeutics, Bayer, Janssen, MSD, Pfizer, Astex Pharmaceuticals, Clovis Oncology, and Roche. Dr. Fizazi reported relationships with Novartis, AstraZeneca, and a dozen other companies.

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

A central aim of prostate cancer treatment is to prolong survival, but trials often overlook another key goal: Improving — or at least maintaining — quality of life (QoL).

The recent American Society of Clinical Oncology (ASCO) 2024 annual meeting dedicated a session to QoL outcomes in men with prostate cancer.

The trials explored the effects of treatment suspension or intensification on health-related QoL as well as interventions to manage side effects in different patient populations.

The first presentation focused on a post hoc analysis of the phase 3 EMBARK trial, which looked at the effect of suspending treatment on health-related QoL in men with nonmetastatic disease at a high risk for biochemical recurrence.

Earlier findings from the trial, presented at ESMO in 2023, showed enzalutamide alone or in combination with androgen deprivation therapy (ADT) was associated with a significant improvement in metastasis-free survival vs placebo plus leuprolide.

The initial trial randomized 1068 patients at a high risk for biochemical recurrence to these three treatment groups and suspended therapy at week 37 if prostate-specific antigen (PSA) levels fell below 0.2 ng/mL. Patients, however, were not randomized into the treatment suspension groups. Treatment resumed if PSA levels rose to ≥ 2.0 ng/mL in patients who had undergone radical prostatectomy or ≥ 5.0 ng/mL in those who had not had surgery.

The post hoc analysis, which assessed patient-reported QoL outcomes following treatment suspension at baseline and every 12 weeks until progression, found no meaningful changes in the worst pain in the past 24 hours, as measured by the Brief Pain Inventory–Short Form.

Patients also reported no meaningful changes in total and physical well-being scores on the Functional Assessment of Cancer Therapy–Prostate (FACT-P) and on the European Quality of Life Five-Dimensions (EuroQol-5D) visual analog scale score, as well as no meaningful changes in sexual activity and urinary and bowel symptoms, based on scores from the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–Prostate 25 (QLQ-PR25).

Hormone treatment-related symptoms on the QLQ-PR25, however, “quickly improved but eventually began to worsen after week 97,” explained lead author Stephen J. Freedland, MD, from Cedars-Sinai Medical Center, Los Angeles, California, who presented the new findings at ASCO.

Dr. Freedland concluded that the EMBARK results show that enzalutamide, with or without ADT, improves metastasis-free survival vs leuprolide alone, without affecting global health-related QoL during treatment or after treatment suspension.

However, Channing J. Paller, MD, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Medicine, Baltimore, Maryland, who was not involved in the research, pointed out that “patient selection is key” when choosing therapies, given that ADT has distinct adverse effects. Comorbidities and adverse effects “must be taken into consideration to help the doctor and patient make more personalized treatment choices.”
 

Treatment Intensification and QoL

Another presentation explored health-related QoL outcomes from the phase 3 PRESTO trial.

The study examined ADT intensification in 504 patients who had high-risk biochemically relapsed nonmetastatic hormone-sensitive prostate cancer and a PSA doubling time of 9 months or less. Patients were randomized to ADT monotherapy with degarelix or leuprolide, ADT plus apalutamide, or ADT plus apalutamide, abiraterone acetate, and prednisone.

In previous data from PRESTO, the combination therapy groups both had significantly longer median PSA progression-free survival than the ADT monotherapy arm.

The latest data looked at the health-related QoL outcomes in the PRESTO population, measured using the Expanded Prostate Cancer Index Composite, the PROMIS Fatigue tool, the Hot Flash Related Daily Interference Scale, and the EuroQol-5D.

Ronald C. Chen, MD, MPH, of the University of Kansas Medical Center, Kansas City, who presented the new findings at ASCO, reported that ADT plus apalutamide improved PSA progression-free survival over ADT alone and did not meaningfully increase common treatment-related symptoms, such as hormonal symptoms, sexual dysfunction, hot flash interference, and fatigue.

However, treatment intensification with triple androgen regimen did not lead to further improvements in PSA progression-free survival but did increase the rate of serious adverse events, the time to testosterone recover, and increased hot flash interference.

PRESTO as well as EMBARK “provide a strong rationale for intensification of androgen blockade in men with high-risk biochemical recurrence after completing primary local therapy” and could even “reduce the need for subsequent treatment,” concluded Dr. Chen.
 

CBT for Managing ADT Side Effects

Up to 80% of men receiving ADT to treat prostate cancer experience night sweats and hot flashes, which are associated with sleep disturbance, anxiety, low mood, and cognitive impairments.

A third trial presented during the session looked at the impact of cognitive-behavioral therapy (CBT) on these side effects of ADT treatment.

Initial findings from the MANCAN study found that CBT delivered by a psychologist reduced the impact of hot flashes and night sweats at 6 weeks.

The MANCAN2 study assessed QoL at 6 months among 162 patients with localized or advanced prostate cancer who underwent at least 6 months of continuous ADT and who experienced more severe hot flashes and night sweats, defined as a score of ≥ 2 on the hot flashes and night sweats problem rating scale.

Study participants were randomized to CBT plus treatment as usual, or treatment as usual alone, with the intervention consisting of two CBT group sessions 4 weeks apart. Between CBT sessions, patients could refer to a booklet and CD, alongside exercises and CBT strategies.

MANCAN2 confirmed that CBT was associated with a significantly greater reduction in hot flash and night sweat scores over standard care alone at 6 weeks. Patients receiving CBT also reported better QoL, sleep, and functional status but those differences did not reach statistical significance.

By 6 months, those in the CBT group still reported better outcomes in each category, but no differences were statistically significant at this time point. Overall, however, 14% of treatment as usual alone patients discontinued ADT at 6 months vs none in the CBT arm.

“Further research is therefore needed to determine whether or not you can make this effect more durable” and to look at “the potential for CBT to support treatment compliance,” said study presenter Simon J. Crabb, PhD, MBBS, from the University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, England.
 

QoL With Radioligand Crossover

Finally, the phase 3 PSMAfore study compared ¹⁷⁷Lu-PSMA-617 with abiraterone or enzalutamide in 468 taxane-naive patients with metastatic castration-resistant prostate cancer who had progressed on a previous androgen receptor pathway inhibitor.

In earlier analyses, Karim Fizazi, MD, PhD, Institut Gustave Roussy, Université Paris-Saclay, Paris, France, reported that ¹⁷⁷Lu-PSMA-617 improved radiographic progression-free survival by 59% over androgen receptor pathway inhibitor therapy but did not lead to significant differences in overall survival.

In a new interim analysis, Dr. Fizazi and colleagues explored outcomes in patients eligible to cross over to ¹⁷⁷Lu-PSMA-617 following androgen receptor pathway inhibitor therapy. Assessments of health-related QoL revealed that ¹⁷⁷Lu-PSMA-617 led to about a 40% improvement in scores on two QoL tools — 41% with FACT-P and 39% with EuroQol-5D.

On subscales of FACT-P, Dr. Fizazi reported that ¹⁷⁷Lu-PSMA-617 was also associated with a significantly longer time to worsening in physical, functional, and emotional well-being over standard therapy. A pain inventory score indicated that ¹⁷⁷Lu-PSMA-617 led to a 31% improvement in the time to worsening pain intensity, as well as a 33% increase in the time to worsening pain interference.

With the treatment having a “favorable safety profile,” Dr. Fizazi said the results suggest ¹⁷⁷Lu-PSMA-617 is a “treatment option” for patients with metastatic castration-resistant prostate cancer who have undergone androgen receptor pathway inhibitor treatment.

MANCAN2 was funded by the UK National Institute for Health and Care Research. EMBARK was funded by Astellas Pharma and Pfizer, the codevelopers of enzalutamide. PRESTO was funded by Alliance Foundation Trials and Johnson & Johnson. PSMAfore was funded by Novartis. Dr. Freedland declared relationships with Pfizer and Astellas Pharma, among others. Paller declared relationships with AstraZeneca, Dendreon, Exelixis, Janssen Oncology, Omnitura, Lilly, and Bayer. Dr. Chen declared relationships with Astellas Pharma, Pfizer, and others. Dr. Crabb declared relationships with AstraZeneca, Bristol-Myers Squibb, Ipsen, Merck, Amgen, Amphista Therapeutics, Bayer, Janssen, MSD, Pfizer, Astex Pharmaceuticals, Clovis Oncology, and Roche. Dr. Fizazi reported relationships with Novartis, AstraZeneca, and a dozen other companies.

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

A central aim of prostate cancer treatment is to prolong survival, but trials often overlook another key goal: Improving — or at least maintaining — quality of life (QoL).

The recent American Society of Clinical Oncology (ASCO) 2024 annual meeting dedicated a session to QoL outcomes in men with prostate cancer.

The trials explored the effects of treatment suspension or intensification on health-related QoL as well as interventions to manage side effects in different patient populations.

The first presentation focused on a post hoc analysis of the phase 3 EMBARK trial, which looked at the effect of suspending treatment on health-related QoL in men with nonmetastatic disease at a high risk for biochemical recurrence.

Earlier findings from the trial, presented at ESMO in 2023, showed enzalutamide alone or in combination with androgen deprivation therapy (ADT) was associated with a significant improvement in metastasis-free survival vs placebo plus leuprolide.

The initial trial randomized 1068 patients at a high risk for biochemical recurrence to these three treatment groups and suspended therapy at week 37 if prostate-specific antigen (PSA) levels fell below 0.2 ng/mL. Patients, however, were not randomized into the treatment suspension groups. Treatment resumed if PSA levels rose to ≥ 2.0 ng/mL in patients who had undergone radical prostatectomy or ≥ 5.0 ng/mL in those who had not had surgery.

The post hoc analysis, which assessed patient-reported QoL outcomes following treatment suspension at baseline and every 12 weeks until progression, found no meaningful changes in the worst pain in the past 24 hours, as measured by the Brief Pain Inventory–Short Form.

Patients also reported no meaningful changes in total and physical well-being scores on the Functional Assessment of Cancer Therapy–Prostate (FACT-P) and on the European Quality of Life Five-Dimensions (EuroQol-5D) visual analog scale score, as well as no meaningful changes in sexual activity and urinary and bowel symptoms, based on scores from the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–Prostate 25 (QLQ-PR25).

Hormone treatment-related symptoms on the QLQ-PR25, however, “quickly improved but eventually began to worsen after week 97,” explained lead author Stephen J. Freedland, MD, from Cedars-Sinai Medical Center, Los Angeles, California, who presented the new findings at ASCO.

Dr. Freedland concluded that the EMBARK results show that enzalutamide, with or without ADT, improves metastasis-free survival vs leuprolide alone, without affecting global health-related QoL during treatment or after treatment suspension.

However, Channing J. Paller, MD, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Medicine, Baltimore, Maryland, who was not involved in the research, pointed out that “patient selection is key” when choosing therapies, given that ADT has distinct adverse effects. Comorbidities and adverse effects “must be taken into consideration to help the doctor and patient make more personalized treatment choices.”
 

Treatment Intensification and QoL

Another presentation explored health-related QoL outcomes from the phase 3 PRESTO trial.

The study examined ADT intensification in 504 patients who had high-risk biochemically relapsed nonmetastatic hormone-sensitive prostate cancer and a PSA doubling time of 9 months or less. Patients were randomized to ADT monotherapy with degarelix or leuprolide, ADT plus apalutamide, or ADT plus apalutamide, abiraterone acetate, and prednisone.

In previous data from PRESTO, the combination therapy groups both had significantly longer median PSA progression-free survival than the ADT monotherapy arm.

The latest data looked at the health-related QoL outcomes in the PRESTO population, measured using the Expanded Prostate Cancer Index Composite, the PROMIS Fatigue tool, the Hot Flash Related Daily Interference Scale, and the EuroQol-5D.

Ronald C. Chen, MD, MPH, of the University of Kansas Medical Center, Kansas City, who presented the new findings at ASCO, reported that ADT plus apalutamide improved PSA progression-free survival over ADT alone and did not meaningfully increase common treatment-related symptoms, such as hormonal symptoms, sexual dysfunction, hot flash interference, and fatigue.

However, treatment intensification with triple androgen regimen did not lead to further improvements in PSA progression-free survival but did increase the rate of serious adverse events, the time to testosterone recover, and increased hot flash interference.

PRESTO as well as EMBARK “provide a strong rationale for intensification of androgen blockade in men with high-risk biochemical recurrence after completing primary local therapy” and could even “reduce the need for subsequent treatment,” concluded Dr. Chen.
 

CBT for Managing ADT Side Effects

Up to 80% of men receiving ADT to treat prostate cancer experience night sweats and hot flashes, which are associated with sleep disturbance, anxiety, low mood, and cognitive impairments.

A third trial presented during the session looked at the impact of cognitive-behavioral therapy (CBT) on these side effects of ADT treatment.

Initial findings from the MANCAN study found that CBT delivered by a psychologist reduced the impact of hot flashes and night sweats at 6 weeks.

The MANCAN2 study assessed QoL at 6 months among 162 patients with localized or advanced prostate cancer who underwent at least 6 months of continuous ADT and who experienced more severe hot flashes and night sweats, defined as a score of ≥ 2 on the hot flashes and night sweats problem rating scale.

Study participants were randomized to CBT plus treatment as usual, or treatment as usual alone, with the intervention consisting of two CBT group sessions 4 weeks apart. Between CBT sessions, patients could refer to a booklet and CD, alongside exercises and CBT strategies.

MANCAN2 confirmed that CBT was associated with a significantly greater reduction in hot flash and night sweat scores over standard care alone at 6 weeks. Patients receiving CBT also reported better QoL, sleep, and functional status but those differences did not reach statistical significance.

By 6 months, those in the CBT group still reported better outcomes in each category, but no differences were statistically significant at this time point. Overall, however, 14% of treatment as usual alone patients discontinued ADT at 6 months vs none in the CBT arm.

“Further research is therefore needed to determine whether or not you can make this effect more durable” and to look at “the potential for CBT to support treatment compliance,” said study presenter Simon J. Crabb, PhD, MBBS, from the University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, England.
 

QoL With Radioligand Crossover

Finally, the phase 3 PSMAfore study compared ¹⁷⁷Lu-PSMA-617 with abiraterone or enzalutamide in 468 taxane-naive patients with metastatic castration-resistant prostate cancer who had progressed on a previous androgen receptor pathway inhibitor.

In earlier analyses, Karim Fizazi, MD, PhD, Institut Gustave Roussy, Université Paris-Saclay, Paris, France, reported that ¹⁷⁷Lu-PSMA-617 improved radiographic progression-free survival by 59% over androgen receptor pathway inhibitor therapy but did not lead to significant differences in overall survival.

In a new interim analysis, Dr. Fizazi and colleagues explored outcomes in patients eligible to cross over to ¹⁷⁷Lu-PSMA-617 following androgen receptor pathway inhibitor therapy. Assessments of health-related QoL revealed that ¹⁷⁷Lu-PSMA-617 led to about a 40% improvement in scores on two QoL tools — 41% with FACT-P and 39% with EuroQol-5D.

On subscales of FACT-P, Dr. Fizazi reported that ¹⁷⁷Lu-PSMA-617 was also associated with a significantly longer time to worsening in physical, functional, and emotional well-being over standard therapy. A pain inventory score indicated that ¹⁷⁷Lu-PSMA-617 led to a 31% improvement in the time to worsening pain intensity, as well as a 33% increase in the time to worsening pain interference.

With the treatment having a “favorable safety profile,” Dr. Fizazi said the results suggest ¹⁷⁷Lu-PSMA-617 is a “treatment option” for patients with metastatic castration-resistant prostate cancer who have undergone androgen receptor pathway inhibitor treatment.

MANCAN2 was funded by the UK National Institute for Health and Care Research. EMBARK was funded by Astellas Pharma and Pfizer, the codevelopers of enzalutamide. PRESTO was funded by Alliance Foundation Trials and Johnson & Johnson. PSMAfore was funded by Novartis. Dr. Freedland declared relationships with Pfizer and Astellas Pharma, among others. Paller declared relationships with AstraZeneca, Dendreon, Exelixis, Janssen Oncology, Omnitura, Lilly, and Bayer. Dr. Chen declared relationships with Astellas Pharma, Pfizer, and others. Dr. Crabb declared relationships with AstraZeneca, Bristol-Myers Squibb, Ipsen, Merck, Amgen, Amphista Therapeutics, Bayer, Janssen, MSD, Pfizer, Astex Pharmaceuticals, Clovis Oncology, and Roche. Dr. Fizazi reported relationships with Novartis, AstraZeneca, and a dozen other companies.

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

LISBON, PORTUGAL — Few people with suspected heart failure and elevated N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels are receiving a diagnosis after a year, reported investigators, who say high rates of hospitalization are common.

Presenting here at the Heart Failure Association of the European Society of Cardiology (HFA-ESC) 2024, researchers shared results from the REVOLUTION-HF study involving almost 8000 people who consulted outpatient primary and secondary care over a 5-year period.

About two thirds of the patients had suspected heart failure; however, less than 30% of the people received a diagnosis within a year.

Yet hospitalization was eight times higher in the suspected heart failure group than in the control group, and all-cause mortality was nearly doubled. The outcomes were even worse in patients with high NT-proBNP levels.

Patients with suspected heart failure are “waiting far too long to see a specialist, and that results in a delay to guideline-directed medical therapy, despite the fact that we’re perfectly happy to slap them all on diuretics,” said study presenter Lisa Anderson, MD, PhD, Cardiovascular Clinical Academic Group, Molecular and Clinical Sciences Research Institute, St George’s Hospital, University of London, England.

“We need to rethink our management of heart failure patients presenting in the community,” she said.

A big gap exists internationally between presentation with heart failure, an elevated NT-proBNP, and confirmatory specialist assessment, she explained.

“It’s a scandal that patients are coming to the GP with signs and symptoms of heart failure, they get tested for natriuretic peptides, and nothing happens,” said co-author Antoni Bayés-Genís, MD, PhD, Heart Institute director, Hospital Universitari Germans Trias i Pujol Catedràtic, Barcelona, Spain.

“These patients may receive an echo, or not, in the coming 12 months,” and “during these 12 months, there is a huge number of heart failure hospitalizations and deaths that could probably be prevented.”
 

Why the Reluctance to Diagnose?

Many issues get in the way of early diagnosis, Dr. Bayés-Genís said. “Inertia, comorbidities, ageism.”

A lot of patients with heart failure are elderly women with some degree of weight gain, he said. “And they come to the clinic with fatigue, so we tell them, ‘Well, that’s normal.”

But “it may not be normal,” he added. “This is a very important topic that we, as a society, need to address.”

There are several “misconceptions” about heart failure, said Ileana L. Piña, MD, MPH, the Robert Stein Chair for Quality and Safety, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, who was not involved in the study.

For example, “we’re all convinced that guideline-directed medical therapy works,” but the evidence is only for patients “with a diagnosis.” In addition, “millions of patients get tested” for heart failure, but they already have a “known diagnosis.”

“When we study these drugs, we’re studying them on patients with manifest disease,” who are only then randomized, Dr. Piña said. “But we seldom see them while they’re developing heart failure. And it’s a process; it doesn’t happen overnight.”

Patients initially often think they may have asthma, and so what follows is an extended period of “uncertainty” and “important time lost” before they finally undergo the assessments that show that they have heart failure, she said.

However, “uncertainty” often lands a patient “in the emergency room or with an unscheduled office visit, where NT-proBNP might get ordered and there’s a long lineup for an echo.”

There are several strengths of the current study, Dr. Piña said, including the fact that 50% of the study population were women, and they were older than a typical trial population. Nevertheless, the results were “eye-opening but not surprising” and, in the end, “disappointing.”

“I agree, we need a revolution, Dr. Anderson,” Dr. Piña said. “The revolution of paying attention to the NT-proBNP when you get it and it’s elevated” and then following through with echocardiography and starting “guideline-directed medical therapy early.”

The diagnosis of heart failure “relies on the presentation of patients with nonspecific signs and symptoms,” such as dyspnea and peripheral edema, “but initiation of guideline-directed medical therapy — life-saving treatment — has to wait until we have a formal echocardiography and specialist clinician assessment,” Dr. Anderson said.

The latest clinical consensus statement from the Heart Failure Association “proposes both rule-in and rule-out NT-proBNP levels for heart failure diagnosis, and obviously we all recognize that it’s important to treat patients as soon as they’re diagnosed,” she explained.
 

REVOLUTION-HF

To examine the risk profile for patients presenting to outpatient care with suspected heart failure, the researchers conducted REVOLUTION-HF, which leveraged nationwide Swedish linked data from general practices, specialists, pharmacies, hospitals, and cause of death registers.

“Really impressively, most of these NT-proBNP tests were coming back within a day,” Dr. Anderson said, “so a really, really good turnaround.”

Individuals were excluded if they had an inpatient admission, echocardiography, or heart failure diagnosis between presentation and the NT-proBNP measurement.

These people were then compared with those presenting to primary or secondary outpatient care for any reason and matched for age, sex, care level, and index year. Both groups were followed up for 1 year.

“Despite this really impressive, almost immediate NT-proBNP testing,” the waiting times to undergo echocardiography were “really disappointing,” Dr. Anderson said.

The median time to first registered echocardiography was 40 days, and only 29% of patients with suspected heart failure received a diagnosis within a year of the index presentation date, which she described as “inadequately slow.”

“And how does this translate to medical therapy?” she asked.
 

Heart Failure Drugs

After the index presentation, the rate of loop diuretic use quadrupled among individuals suspected of having heart failure, but there was a “muted response” when it came to the prescribing of beta-blockers and the other pillars of heart failure therapy, which Dr. Anderson called “very disappointing.”

For outcomes after the index presentation, the rate of hospitalization was much higher in the group with suspected heart failure than in the control group (16.1 vs 2.2 events per 100 person-years). And all-cause mortality occurred more often in the group with suspected heart failure than in the control group (10.3 vs 6.5 events per 100 person-years).

Among patients with NT-proBNP levels of 2000 ng/L, there was a “rapid” onset of hospitalization “within the first few days” of the index presentation, which was tracked by a more linear rise in all-cause deaths, Dr. Anderson reported.

In the United Kingdom, “we are very proud of our 2- and 6-week pathways,” which stipulate that suspected heart failure patients with NT-proBNP levels between 400 and 2000 ng/L are to have a specialist assessment and transthoracic echocardiography within 6 weeks; for those with levels > 2000 ng/L, that interval is accelerated to 2 weeks, she said.

The current results show that “2 weeks is too slow.” And looking at the rest of the cohort with lower NT-proBNP levels, “patients have already been admitted and died” by 6 weeks, she said.

When patients are stratified by age, “you get exactly what you would expect,” Dr. Anderson said. “The older patients are the most at risk” for both hospitalization and all-cause mortality.
 

A version of this article appeared on Medscape.com.

LISBON, PORTUGAL — Few people with suspected heart failure and elevated N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels are receiving a diagnosis after a year, reported investigators, who say high rates of hospitalization are common.

Presenting here at the Heart Failure Association of the European Society of Cardiology (HFA-ESC) 2024, researchers shared results from the REVOLUTION-HF study involving almost 8000 people who consulted outpatient primary and secondary care over a 5-year period.

About two thirds of the patients had suspected heart failure; however, less than 30% of the people received a diagnosis within a year.

Yet hospitalization was eight times higher in the suspected heart failure group than in the control group, and all-cause mortality was nearly doubled. The outcomes were even worse in patients with high NT-proBNP levels.

Patients with suspected heart failure are “waiting far too long to see a specialist, and that results in a delay to guideline-directed medical therapy, despite the fact that we’re perfectly happy to slap them all on diuretics,” said study presenter Lisa Anderson, MD, PhD, Cardiovascular Clinical Academic Group, Molecular and Clinical Sciences Research Institute, St George’s Hospital, University of London, England.

“We need to rethink our management of heart failure patients presenting in the community,” she said.

A big gap exists internationally between presentation with heart failure, an elevated NT-proBNP, and confirmatory specialist assessment, she explained.

“It’s a scandal that patients are coming to the GP with signs and symptoms of heart failure, they get tested for natriuretic peptides, and nothing happens,” said co-author Antoni Bayés-Genís, MD, PhD, Heart Institute director, Hospital Universitari Germans Trias i Pujol Catedràtic, Barcelona, Spain.

“These patients may receive an echo, or not, in the coming 12 months,” and “during these 12 months, there is a huge number of heart failure hospitalizations and deaths that could probably be prevented.”
 

Why the Reluctance to Diagnose?

Many issues get in the way of early diagnosis, Dr. Bayés-Genís said. “Inertia, comorbidities, ageism.”

A lot of patients with heart failure are elderly women with some degree of weight gain, he said. “And they come to the clinic with fatigue, so we tell them, ‘Well, that’s normal.”

But “it may not be normal,” he added. “This is a very important topic that we, as a society, need to address.”

There are several “misconceptions” about heart failure, said Ileana L. Piña, MD, MPH, the Robert Stein Chair for Quality and Safety, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, who was not involved in the study.

For example, “we’re all convinced that guideline-directed medical therapy works,” but the evidence is only for patients “with a diagnosis.” In addition, “millions of patients get tested” for heart failure, but they already have a “known diagnosis.”

“When we study these drugs, we’re studying them on patients with manifest disease,” who are only then randomized, Dr. Piña said. “But we seldom see them while they’re developing heart failure. And it’s a process; it doesn’t happen overnight.”

Patients initially often think they may have asthma, and so what follows is an extended period of “uncertainty” and “important time lost” before they finally undergo the assessments that show that they have heart failure, she said.

However, “uncertainty” often lands a patient “in the emergency room or with an unscheduled office visit, where NT-proBNP might get ordered and there’s a long lineup for an echo.”

There are several strengths of the current study, Dr. Piña said, including the fact that 50% of the study population were women, and they were older than a typical trial population. Nevertheless, the results were “eye-opening but not surprising” and, in the end, “disappointing.”

“I agree, we need a revolution, Dr. Anderson,” Dr. Piña said. “The revolution of paying attention to the NT-proBNP when you get it and it’s elevated” and then following through with echocardiography and starting “guideline-directed medical therapy early.”

The diagnosis of heart failure “relies on the presentation of patients with nonspecific signs and symptoms,” such as dyspnea and peripheral edema, “but initiation of guideline-directed medical therapy — life-saving treatment — has to wait until we have a formal echocardiography and specialist clinician assessment,” Dr. Anderson said.

The latest clinical consensus statement from the Heart Failure Association “proposes both rule-in and rule-out NT-proBNP levels for heart failure diagnosis, and obviously we all recognize that it’s important to treat patients as soon as they’re diagnosed,” she explained.
 

REVOLUTION-HF

To examine the risk profile for patients presenting to outpatient care with suspected heart failure, the researchers conducted REVOLUTION-HF, which leveraged nationwide Swedish linked data from general practices, specialists, pharmacies, hospitals, and cause of death registers.

“Really impressively, most of these NT-proBNP tests were coming back within a day,” Dr. Anderson said, “so a really, really good turnaround.”

Individuals were excluded if they had an inpatient admission, echocardiography, or heart failure diagnosis between presentation and the NT-proBNP measurement.

These people were then compared with those presenting to primary or secondary outpatient care for any reason and matched for age, sex, care level, and index year. Both groups were followed up for 1 year.

“Despite this really impressive, almost immediate NT-proBNP testing,” the waiting times to undergo echocardiography were “really disappointing,” Dr. Anderson said.

The median time to first registered echocardiography was 40 days, and only 29% of patients with suspected heart failure received a diagnosis within a year of the index presentation date, which she described as “inadequately slow.”

“And how does this translate to medical therapy?” she asked.
 

Heart Failure Drugs

After the index presentation, the rate of loop diuretic use quadrupled among individuals suspected of having heart failure, but there was a “muted response” when it came to the prescribing of beta-blockers and the other pillars of heart failure therapy, which Dr. Anderson called “very disappointing.”

For outcomes after the index presentation, the rate of hospitalization was much higher in the group with suspected heart failure than in the control group (16.1 vs 2.2 events per 100 person-years). And all-cause mortality occurred more often in the group with suspected heart failure than in the control group (10.3 vs 6.5 events per 100 person-years).

Among patients with NT-proBNP levels of 2000 ng/L, there was a “rapid” onset of hospitalization “within the first few days” of the index presentation, which was tracked by a more linear rise in all-cause deaths, Dr. Anderson reported.

In the United Kingdom, “we are very proud of our 2- and 6-week pathways,” which stipulate that suspected heart failure patients with NT-proBNP levels between 400 and 2000 ng/L are to have a specialist assessment and transthoracic echocardiography within 6 weeks; for those with levels > 2000 ng/L, that interval is accelerated to 2 weeks, she said.

The current results show that “2 weeks is too slow.” And looking at the rest of the cohort with lower NT-proBNP levels, “patients have already been admitted and died” by 6 weeks, she said.

When patients are stratified by age, “you get exactly what you would expect,” Dr. Anderson said. “The older patients are the most at risk” for both hospitalization and all-cause mortality.
 

A version of this article appeared on Medscape.com.

LISBON, PORTUGAL — Few people with suspected heart failure and elevated N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels are receiving a diagnosis after a year, reported investigators, who say high rates of hospitalization are common.

Presenting here at the Heart Failure Association of the European Society of Cardiology (HFA-ESC) 2024, researchers shared results from the REVOLUTION-HF study involving almost 8000 people who consulted outpatient primary and secondary care over a 5-year period.

About two thirds of the patients had suspected heart failure; however, less than 30% of the people received a diagnosis within a year.

Yet hospitalization was eight times higher in the suspected heart failure group than in the control group, and all-cause mortality was nearly doubled. The outcomes were even worse in patients with high NT-proBNP levels.

Patients with suspected heart failure are “waiting far too long to see a specialist, and that results in a delay to guideline-directed medical therapy, despite the fact that we’re perfectly happy to slap them all on diuretics,” said study presenter Lisa Anderson, MD, PhD, Cardiovascular Clinical Academic Group, Molecular and Clinical Sciences Research Institute, St George’s Hospital, University of London, England.

“We need to rethink our management of heart failure patients presenting in the community,” she said.

A big gap exists internationally between presentation with heart failure, an elevated NT-proBNP, and confirmatory specialist assessment, she explained.

“It’s a scandal that patients are coming to the GP with signs and symptoms of heart failure, they get tested for natriuretic peptides, and nothing happens,” said co-author Antoni Bayés-Genís, MD, PhD, Heart Institute director, Hospital Universitari Germans Trias i Pujol Catedràtic, Barcelona, Spain.

“These patients may receive an echo, or not, in the coming 12 months,” and “during these 12 months, there is a huge number of heart failure hospitalizations and deaths that could probably be prevented.”
 

Why the Reluctance to Diagnose?

Many issues get in the way of early diagnosis, Dr. Bayés-Genís said. “Inertia, comorbidities, ageism.”

A lot of patients with heart failure are elderly women with some degree of weight gain, he said. “And they come to the clinic with fatigue, so we tell them, ‘Well, that’s normal.”

But “it may not be normal,” he added. “This is a very important topic that we, as a society, need to address.”

There are several “misconceptions” about heart failure, said Ileana L. Piña, MD, MPH, the Robert Stein Chair for Quality and Safety, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, who was not involved in the study.

For example, “we’re all convinced that guideline-directed medical therapy works,” but the evidence is only for patients “with a diagnosis.” In addition, “millions of patients get tested” for heart failure, but they already have a “known diagnosis.”

“When we study these drugs, we’re studying them on patients with manifest disease,” who are only then randomized, Dr. Piña said. “But we seldom see them while they’re developing heart failure. And it’s a process; it doesn’t happen overnight.”

Patients initially often think they may have asthma, and so what follows is an extended period of “uncertainty” and “important time lost” before they finally undergo the assessments that show that they have heart failure, she said.

However, “uncertainty” often lands a patient “in the emergency room or with an unscheduled office visit, where NT-proBNP might get ordered and there’s a long lineup for an echo.”

There are several strengths of the current study, Dr. Piña said, including the fact that 50% of the study population were women, and they were older than a typical trial population. Nevertheless, the results were “eye-opening but not surprising” and, in the end, “disappointing.”

“I agree, we need a revolution, Dr. Anderson,” Dr. Piña said. “The revolution of paying attention to the NT-proBNP when you get it and it’s elevated” and then following through with echocardiography and starting “guideline-directed medical therapy early.”

The diagnosis of heart failure “relies on the presentation of patients with nonspecific signs and symptoms,” such as dyspnea and peripheral edema, “but initiation of guideline-directed medical therapy — life-saving treatment — has to wait until we have a formal echocardiography and specialist clinician assessment,” Dr. Anderson said.

The latest clinical consensus statement from the Heart Failure Association “proposes both rule-in and rule-out NT-proBNP levels for heart failure diagnosis, and obviously we all recognize that it’s important to treat patients as soon as they’re diagnosed,” she explained.
 

REVOLUTION-HF

To examine the risk profile for patients presenting to outpatient care with suspected heart failure, the researchers conducted REVOLUTION-HF, which leveraged nationwide Swedish linked data from general practices, specialists, pharmacies, hospitals, and cause of death registers.

“Really impressively, most of these NT-proBNP tests were coming back within a day,” Dr. Anderson said, “so a really, really good turnaround.”

Individuals were excluded if they had an inpatient admission, echocardiography, or heart failure diagnosis between presentation and the NT-proBNP measurement.

These people were then compared with those presenting to primary or secondary outpatient care for any reason and matched for age, sex, care level, and index year. Both groups were followed up for 1 year.

“Despite this really impressive, almost immediate NT-proBNP testing,” the waiting times to undergo echocardiography were “really disappointing,” Dr. Anderson said.

The median time to first registered echocardiography was 40 days, and only 29% of patients with suspected heart failure received a diagnosis within a year of the index presentation date, which she described as “inadequately slow.”

“And how does this translate to medical therapy?” she asked.
 

Heart Failure Drugs

After the index presentation, the rate of loop diuretic use quadrupled among individuals suspected of having heart failure, but there was a “muted response” when it came to the prescribing of beta-blockers and the other pillars of heart failure therapy, which Dr. Anderson called “very disappointing.”

For outcomes after the index presentation, the rate of hospitalization was much higher in the group with suspected heart failure than in the control group (16.1 vs 2.2 events per 100 person-years). And all-cause mortality occurred more often in the group with suspected heart failure than in the control group (10.3 vs 6.5 events per 100 person-years).

Among patients with NT-proBNP levels of 2000 ng/L, there was a “rapid” onset of hospitalization “within the first few days” of the index presentation, which was tracked by a more linear rise in all-cause deaths, Dr. Anderson reported.

In the United Kingdom, “we are very proud of our 2- and 6-week pathways,” which stipulate that suspected heart failure patients with NT-proBNP levels between 400 and 2000 ng/L are to have a specialist assessment and transthoracic echocardiography within 6 weeks; for those with levels > 2000 ng/L, that interval is accelerated to 2 weeks, she said.

The current results show that “2 weeks is too slow.” And looking at the rest of the cohort with lower NT-proBNP levels, “patients have already been admitted and died” by 6 weeks, she said.

When patients are stratified by age, “you get exactly what you would expect,” Dr. Anderson said. “The older patients are the most at risk” for both hospitalization and all-cause mortality.
 

A version of this article appeared on Medscape.com.

LISBON, PORTUGAL — The addition of a yearlong customized yoga therapy intervention to guideline-directed medical therapy (GDMT) appears to significantly improve heart failure measures associated with long-term prognosis, findings from an Indian study suggested.

The research, presented at the Heart Failure Association of the European Society of Cardiology (HFA-ESC) 2024 congress, involved 105 patients assigned to yoga plus GDMT or GDMT alone and demonstrated that there was a large shift in the New York Heart Association (NYHA) functional class from baseline to the 52-week follow-up.

“Yoga therapy has a beneficial impact on heart failure patients on optimal medical management,” said study presenter Ajit Singh, MD, Department of Medicine, Kasturba Medical College, Manipal, Karnataka, India, and the study “demonstrated an overall improvement in left ventricle dimensions and function.”

However, because patients were followed every day and almost a quarter had dropped out by 6 months, the study was “a challenge,” he noted. Nevertheless, the addition of yoga to GDMT could be a “game changer if we try for longer duration.”

For yoga therapy to be considered in clinical practice, a randomized study is required, said session cochair Dana Dawson, MD, PhD, professor of cardiovascular medicine and lead of the Cardiology and Cardiovascular Research Unit, University of Aberdeen, Scotland.

Patients in the current analysis, however, were not randomly allocated to treatment group, which resulted in baseline discrepancies that made the groups “incomparable,” Dr. Dawson explained.

Still, the study showed that yoga is feasible in this patient group and that, even just comparing baseline and follow-up outcomes in the yoga group, there were some significant results.

“It is effective in implementing a change,” she said, “and whether that change is clinically effective needs to be tested in a clinic in a randomized study.”
 

Why Yoga May Be Particularly Effective

Yoga may be different from other exercise and lifestyle interventions because it is “also about meditation and meeting with your own self,” which corresponds to a form of cognitive behavioral therapy, albeit “conducted in singular manner,” she added.

“It’s not going to be everyone’s cup of tea, and not everyone is going to be inclined to do it,” but it could be suitable in countries where yoga is more commonly practiced as a behavioral, as opposed to lifestyle, intervention, said Dr. Dawson.

Heart failure is a “complex chronic disease” that is a “prime cause of concern for healthcare sectors worldwide,” not least in India, where there is a “very high prevalence” of the disease, Dr. Singh noted.

Evidence from the literature indicates that yoga and other lifestyle modifications can improve the quality of life of patients with heart failure, alongside measures such as left ventricular ejection fraction (LVEF) and NYHA functional class, he said. However, the researchers did not find any study that looked at yoga therapy as an adjunct to standard-of-care treatment.
 

How Yoga Was Applied

They recruited patients aged 30-70 years with persistent heart failure symptoms, an LVEF of < 45%, and NYHA class III or lower heart failure. All participants had undergone a cardiac procedure 6-12 months previously, and all were receiving optimal GDMT.

Patients were assigned in a nonrandomized fashion to GDMT with or without a customized yoga program. Eight forms of pranayama breath work, meditation, and relaxation techniques were taught to patients in the yoga group by experienced hospital faculty.

They were supervised for 1 week and then advised to continue self-administered yoga at home once a week for 45 minutes. After each home session, an instructor followed up with each study participant to monitor progress.

All participants were assessed with echocardiography and other measures, including physical activities, to determine NYHA functional status at baseline, 6 months, and 1 year.

Of the 110 patients recruited, 25 had dropped out by 6 months. Of the remaining 85 patients included in the analysis, 40 were assigned to the yoga group. The average age was 49 years, and 70 (82%) of the participants were men. The lack of women in the study is a “major drawback,” Dr. Singh noted.

Women did not want to participate, he explained, “because they were afraid to get the follow-up,” saying, “We will not be able to follow this yoga therapy for 1 year.”

After 52 weeks, patients in the yoga group had significantly greater reductions from baseline in systolic and diastolic blood pressure, heart rate, and body mass index than those in the GDMT-alone group (P < .05 for all).

Patients in the yoga group also experienced significantly greater improvements in ejection fraction, increasing from an average of 41.5% to 44.4% over the course of the study. In contrast, ejection fraction decreased from 42.3% to 41.6% in the GDMT-alone group (P < .05).

Crucially, there was a marked improvement in the NYHA class in the yoga group.

With yoga, the proportion of patients with class I heart failure increased from 12% to 47% over the 52 weeks of the study, whereas the proportion with class II heart failure decreased from 57% to 30%, and the proportion with class III heart failure decreased from 30% to 12% (P <  .001). In both the yoga and GDMT-alone groups, the proportion of patients with class IV disease increased from 0% to about 10%.

No funding was declared. No relevant financial relationships were declared.
 

A version of this article appeared on Medscape.com.

LISBON, PORTUGAL — The addition of a yearlong customized yoga therapy intervention to guideline-directed medical therapy (GDMT) appears to significantly improve heart failure measures associated with long-term prognosis, findings from an Indian study suggested.

The research, presented at the Heart Failure Association of the European Society of Cardiology (HFA-ESC) 2024 congress, involved 105 patients assigned to yoga plus GDMT or GDMT alone and demonstrated that there was a large shift in the New York Heart Association (NYHA) functional class from baseline to the 52-week follow-up.

“Yoga therapy has a beneficial impact on heart failure patients on optimal medical management,” said study presenter Ajit Singh, MD, Department of Medicine, Kasturba Medical College, Manipal, Karnataka, India, and the study “demonstrated an overall improvement in left ventricle dimensions and function.”

However, because patients were followed every day and almost a quarter had dropped out by 6 months, the study was “a challenge,” he noted. Nevertheless, the addition of yoga to GDMT could be a “game changer if we try for longer duration.”

For yoga therapy to be considered in clinical practice, a randomized study is required, said session cochair Dana Dawson, MD, PhD, professor of cardiovascular medicine and lead of the Cardiology and Cardiovascular Research Unit, University of Aberdeen, Scotland.

Patients in the current analysis, however, were not randomly allocated to treatment group, which resulted in baseline discrepancies that made the groups “incomparable,” Dr. Dawson explained.

Still, the study showed that yoga is feasible in this patient group and that, even just comparing baseline and follow-up outcomes in the yoga group, there were some significant results.

“It is effective in implementing a change,” she said, “and whether that change is clinically effective needs to be tested in a clinic in a randomized study.”
 

Why Yoga May Be Particularly Effective

Yoga may be different from other exercise and lifestyle interventions because it is “also about meditation and meeting with your own self,” which corresponds to a form of cognitive behavioral therapy, albeit “conducted in singular manner,” she added.

“It’s not going to be everyone’s cup of tea, and not everyone is going to be inclined to do it,” but it could be suitable in countries where yoga is more commonly practiced as a behavioral, as opposed to lifestyle, intervention, said Dr. Dawson.

Heart failure is a “complex chronic disease” that is a “prime cause of concern for healthcare sectors worldwide,” not least in India, where there is a “very high prevalence” of the disease, Dr. Singh noted.

Evidence from the literature indicates that yoga and other lifestyle modifications can improve the quality of life of patients with heart failure, alongside measures such as left ventricular ejection fraction (LVEF) and NYHA functional class, he said. However, the researchers did not find any study that looked at yoga therapy as an adjunct to standard-of-care treatment.
 

How Yoga Was Applied

They recruited patients aged 30-70 years with persistent heart failure symptoms, an LVEF of < 45%, and NYHA class III or lower heart failure. All participants had undergone a cardiac procedure 6-12 months previously, and all were receiving optimal GDMT.

Patients were assigned in a nonrandomized fashion to GDMT with or without a customized yoga program. Eight forms of pranayama breath work, meditation, and relaxation techniques were taught to patients in the yoga group by experienced hospital faculty.

They were supervised for 1 week and then advised to continue self-administered yoga at home once a week for 45 minutes. After each home session, an instructor followed up with each study participant to monitor progress.

All participants were assessed with echocardiography and other measures, including physical activities, to determine NYHA functional status at baseline, 6 months, and 1 year.

Of the 110 patients recruited, 25 had dropped out by 6 months. Of the remaining 85 patients included in the analysis, 40 were assigned to the yoga group. The average age was 49 years, and 70 (82%) of the participants were men. The lack of women in the study is a “major drawback,” Dr. Singh noted.

Women did not want to participate, he explained, “because they were afraid to get the follow-up,” saying, “We will not be able to follow this yoga therapy for 1 year.”

After 52 weeks, patients in the yoga group had significantly greater reductions from baseline in systolic and diastolic blood pressure, heart rate, and body mass index than those in the GDMT-alone group (P < .05 for all).

Patients in the yoga group also experienced significantly greater improvements in ejection fraction, increasing from an average of 41.5% to 44.4% over the course of the study. In contrast, ejection fraction decreased from 42.3% to 41.6% in the GDMT-alone group (P < .05).

Crucially, there was a marked improvement in the NYHA class in the yoga group.

With yoga, the proportion of patients with class I heart failure increased from 12% to 47% over the 52 weeks of the study, whereas the proportion with class II heart failure decreased from 57% to 30%, and the proportion with class III heart failure decreased from 30% to 12% (P <  .001). In both the yoga and GDMT-alone groups, the proportion of patients with class IV disease increased from 0% to about 10%.

No funding was declared. No relevant financial relationships were declared.
 

A version of this article appeared on Medscape.com.

LISBON, PORTUGAL — The addition of a yearlong customized yoga therapy intervention to guideline-directed medical therapy (GDMT) appears to significantly improve heart failure measures associated with long-term prognosis, findings from an Indian study suggested.

The research, presented at the Heart Failure Association of the European Society of Cardiology (HFA-ESC) 2024 congress, involved 105 patients assigned to yoga plus GDMT or GDMT alone and demonstrated that there was a large shift in the New York Heart Association (NYHA) functional class from baseline to the 52-week follow-up.

“Yoga therapy has a beneficial impact on heart failure patients on optimal medical management,” said study presenter Ajit Singh, MD, Department of Medicine, Kasturba Medical College, Manipal, Karnataka, India, and the study “demonstrated an overall improvement in left ventricle dimensions and function.”

However, because patients were followed every day and almost a quarter had dropped out by 6 months, the study was “a challenge,” he noted. Nevertheless, the addition of yoga to GDMT could be a “game changer if we try for longer duration.”

For yoga therapy to be considered in clinical practice, a randomized study is required, said session cochair Dana Dawson, MD, PhD, professor of cardiovascular medicine and lead of the Cardiology and Cardiovascular Research Unit, University of Aberdeen, Scotland.

Patients in the current analysis, however, were not randomly allocated to treatment group, which resulted in baseline discrepancies that made the groups “incomparable,” Dr. Dawson explained.

Still, the study showed that yoga is feasible in this patient group and that, even just comparing baseline and follow-up outcomes in the yoga group, there were some significant results.

“It is effective in implementing a change,” she said, “and whether that change is clinically effective needs to be tested in a clinic in a randomized study.”
 

Why Yoga May Be Particularly Effective

Yoga may be different from other exercise and lifestyle interventions because it is “also about meditation and meeting with your own self,” which corresponds to a form of cognitive behavioral therapy, albeit “conducted in singular manner,” she added.

“It’s not going to be everyone’s cup of tea, and not everyone is going to be inclined to do it,” but it could be suitable in countries where yoga is more commonly practiced as a behavioral, as opposed to lifestyle, intervention, said Dr. Dawson.

Heart failure is a “complex chronic disease” that is a “prime cause of concern for healthcare sectors worldwide,” not least in India, where there is a “very high prevalence” of the disease, Dr. Singh noted.

Evidence from the literature indicates that yoga and other lifestyle modifications can improve the quality of life of patients with heart failure, alongside measures such as left ventricular ejection fraction (LVEF) and NYHA functional class, he said. However, the researchers did not find any study that looked at yoga therapy as an adjunct to standard-of-care treatment.
 

How Yoga Was Applied

They recruited patients aged 30-70 years with persistent heart failure symptoms, an LVEF of < 45%, and NYHA class III or lower heart failure. All participants had undergone a cardiac procedure 6-12 months previously, and all were receiving optimal GDMT.

Patients were assigned in a nonrandomized fashion to GDMT with or without a customized yoga program. Eight forms of pranayama breath work, meditation, and relaxation techniques were taught to patients in the yoga group by experienced hospital faculty.

They were supervised for 1 week and then advised to continue self-administered yoga at home once a week for 45 minutes. After each home session, an instructor followed up with each study participant to monitor progress.

All participants were assessed with echocardiography and other measures, including physical activities, to determine NYHA functional status at baseline, 6 months, and 1 year.

Of the 110 patients recruited, 25 had dropped out by 6 months. Of the remaining 85 patients included in the analysis, 40 were assigned to the yoga group. The average age was 49 years, and 70 (82%) of the participants were men. The lack of women in the study is a “major drawback,” Dr. Singh noted.

Women did not want to participate, he explained, “because they were afraid to get the follow-up,” saying, “We will not be able to follow this yoga therapy for 1 year.”

After 52 weeks, patients in the yoga group had significantly greater reductions from baseline in systolic and diastolic blood pressure, heart rate, and body mass index than those in the GDMT-alone group (P < .05 for all).

Patients in the yoga group also experienced significantly greater improvements in ejection fraction, increasing from an average of 41.5% to 44.4% over the course of the study. In contrast, ejection fraction decreased from 42.3% to 41.6% in the GDMT-alone group (P < .05).

Crucially, there was a marked improvement in the NYHA class in the yoga group.

With yoga, the proportion of patients with class I heart failure increased from 12% to 47% over the 52 weeks of the study, whereas the proportion with class II heart failure decreased from 57% to 30%, and the proportion with class III heart failure decreased from 30% to 12% (P <  .001). In both the yoga and GDMT-alone groups, the proportion of patients with class IV disease increased from 0% to about 10%.

No funding was declared. No relevant financial relationships were declared.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Some vulnerable older patients with untreated metastatic pancreatic cancer can benefit from chemotherapy, but only if they can tolerate enough cycles of treatment, according to results of the randomized phase 2 GIANT study.

METHODOLOGY:

Pancreatic cancer is most often diagnosed in adults aged 65 years or older. Providing cancer treatment for this older, often vulnerable, population comes with significant challenges and can lead to worse survival.

To examine real-world outcomes of older adults with untreated metastatic pancreatic cancer, researchers recruited patients aged 70 years or older and performed a geriatric assessment to identify comorbidities, cognitive issues, and other geriatric abnormalities.

Those who were deemed “fit” (ie, with no geriatric abnormalities) were assigned to receive off-study standard-of-care treatment, whereas those classified as “frail” (ie, with severe abnormalities) received off-study supportive care.

The remaining 176 “vulnerable” patients with mild to moderate geriatric abnormalities completed a geriatric and quality-of-life assessment and were then randomly assigned to receive either dose-reduced 5-fluorouracil (5-FU), leucovorin plus liposomal irinotecan (n = 88) or modified gemcitabine plus nab-paclitaxel (n = 88) every 2 weeks. Ultimately, 79 patients started the 5-FU combination and 75 received gemcitabine plus nab-paclitaxel. Patients were assessed every 8 weeks until disease progression or intolerance.

Overall, patients had a median age of 77 years; 61.9% were aged 75 years or older. About half were female, and 81.5% were White. The majority (87.5%) had a performance status of 0 or 1.

TAKEAWAY:

• Median overall survival was 4.7 months in the gemcitabine plus nab-paclitaxel arm and 4.4 months in the 5-FU combination group, with no significant survival difference observed between the two arms (P = .72).
• When the overall survival analysis was restricted to patients who received at least 4 weeks, or two cycles, of treatment (about 62% of patients), the median overall survival across the two treatment arms reached 8.0 months, in line with expectations for these regimens.
• Patient stratification revealed that those with a performance status of 2 had significantly worse overall survival than those with a status of 0: 1.4 months vs 6.9 months, respectively (hazard ratio [HR], 2.77; P < .001). A similar divide was seen when patients were stratified by physical/functional status and well-being. Age, however, did not significantly influence the results.
• Overall, more than half of patients experienced grade 3 or higher adverse events. Just over 38% of patients received only one to three cycles of therapy, whereas 26% remained on treatment for 12 or more cycles. The adverse event rates were similar between the two regimens, but the toxicity profile was slightly different — the researchers, for instance, observed more peripheral neuropathy with gemcitabine plus nab-paclitaxel and more diarrhea in the 5-FU combination arm.

IN PRACTICE:

• Overall, the “survival outcomes among vulnerable older patients were lower than expected, with high percentage of patients not able to start treatment, or complete one month of therapy due to clinical deterioration,” said study presenter Efrat Dotan, MD, chief, Division of Gastrointestinal Medical Oncology, Fox Chase Cancer Center, Philadelphia. 
• “For vulnerable older adults who can tolerate treatment, these two regimens provide clinicians with options for tailoring therapy based on toxicity profile,” Dr. Dotan added. But “tools are needed to better identify patients who can benefit from treatment.”
• The results underline the need to perform geriatric assessments, as opposed to merely looking at performance status, commented David F. Chang, PhD, MS, MBBS, professor of Surgical Oncology, University of Glasgow, Scotland, who was not involved in the study. 

SOURCE:

The research, presented at the 2024 annual meeting of the American Society of Clinical Oncology, was funded by the National Cancer Institute and the Eastern Cooperative Oncology Group.

LIMITATIONS:

Dr. Chang noted that the study did not reveal which treatment regimen was more effective.

DISCLOSURES:

Dr. Dotan declared relationships with Agenus, Amgen, G1 Therapeutics, Incyte, Olympus, and Taiho Pharmaceutical and institutional relationships with Dragonfly Therapeutics, Gilead Sciences, Ipsen, Kinnate Biopharma, Leap Therapeutics, Lilly, Lutris, NGM Biopharmaceuticals, Relay Therapeutics, and Zymeworks. Dr. Chang declared relationships with Immodulon Therapeutics and Mylan and institutional relationships with AstraZeneca, BMS GmbH & Co. KG, Immodulon Therapeutics, and Merck.

A version of this article appeared on Medscape.com.

TOPLINE:

Some vulnerable older patients with untreated metastatic pancreatic cancer can benefit from chemotherapy, but only if they can tolerate enough cycles of treatment, according to results of the randomized phase 2 GIANT study.

METHODOLOGY:

Pancreatic cancer is most often diagnosed in adults aged 65 years or older. Providing cancer treatment for this older, often vulnerable, population comes with significant challenges and can lead to worse survival.

To examine real-world outcomes of older adults with untreated metastatic pancreatic cancer, researchers recruited patients aged 70 years or older and performed a geriatric assessment to identify comorbidities, cognitive issues, and other geriatric abnormalities.

Those who were deemed “fit” (ie, with no geriatric abnormalities) were assigned to receive off-study standard-of-care treatment, whereas those classified as “frail” (ie, with severe abnormalities) received off-study supportive care.

The remaining 176 “vulnerable” patients with mild to moderate geriatric abnormalities completed a geriatric and quality-of-life assessment and were then randomly assigned to receive either dose-reduced 5-fluorouracil (5-FU), leucovorin plus liposomal irinotecan (n = 88) or modified gemcitabine plus nab-paclitaxel (n = 88) every 2 weeks. Ultimately, 79 patients started the 5-FU combination and 75 received gemcitabine plus nab-paclitaxel. Patients were assessed every 8 weeks until disease progression or intolerance.

Overall, patients had a median age of 77 years; 61.9% were aged 75 years or older. About half were female, and 81.5% were White. The majority (87.5%) had a performance status of 0 or 1.

TAKEAWAY:

• Median overall survival was 4.7 months in the gemcitabine plus nab-paclitaxel arm and 4.4 months in the 5-FU combination group, with no significant survival difference observed between the two arms (P = .72).
• When the overall survival analysis was restricted to patients who received at least 4 weeks, or two cycles, of treatment (about 62% of patients), the median overall survival across the two treatment arms reached 8.0 months, in line with expectations for these regimens.
• Patient stratification revealed that those with a performance status of 2 had significantly worse overall survival than those with a status of 0: 1.4 months vs 6.9 months, respectively (hazard ratio [HR], 2.77; P < .001). A similar divide was seen when patients were stratified by physical/functional status and well-being. Age, however, did not significantly influence the results.
• Overall, more than half of patients experienced grade 3 or higher adverse events. Just over 38% of patients received only one to three cycles of therapy, whereas 26% remained on treatment for 12 or more cycles. The adverse event rates were similar between the two regimens, but the toxicity profile was slightly different — the researchers, for instance, observed more peripheral neuropathy with gemcitabine plus nab-paclitaxel and more diarrhea in the 5-FU combination arm.

IN PRACTICE:

• Overall, the “survival outcomes among vulnerable older patients were lower than expected, with high percentage of patients not able to start treatment, or complete one month of therapy due to clinical deterioration,” said study presenter Efrat Dotan, MD, chief, Division of Gastrointestinal Medical Oncology, Fox Chase Cancer Center, Philadelphia. 
• “For vulnerable older adults who can tolerate treatment, these two regimens provide clinicians with options for tailoring therapy based on toxicity profile,” Dr. Dotan added. But “tools are needed to better identify patients who can benefit from treatment.”
• The results underline the need to perform geriatric assessments, as opposed to merely looking at performance status, commented David F. Chang, PhD, MS, MBBS, professor of Surgical Oncology, University of Glasgow, Scotland, who was not involved in the study. 

SOURCE:

The research, presented at the 2024 annual meeting of the American Society of Clinical Oncology, was funded by the National Cancer Institute and the Eastern Cooperative Oncology Group.

LIMITATIONS:

Dr. Chang noted that the study did not reveal which treatment regimen was more effective.

DISCLOSURES:

Dr. Dotan declared relationships with Agenus, Amgen, G1 Therapeutics, Incyte, Olympus, and Taiho Pharmaceutical and institutional relationships with Dragonfly Therapeutics, Gilead Sciences, Ipsen, Kinnate Biopharma, Leap Therapeutics, Lilly, Lutris, NGM Biopharmaceuticals, Relay Therapeutics, and Zymeworks. Dr. Chang declared relationships with Immodulon Therapeutics and Mylan and institutional relationships with AstraZeneca, BMS GmbH & Co. KG, Immodulon Therapeutics, and Merck.

A version of this article appeared on Medscape.com.

TOPLINE:

Some vulnerable older patients with untreated metastatic pancreatic cancer can benefit from chemotherapy, but only if they can tolerate enough cycles of treatment, according to results of the randomized phase 2 GIANT study.

METHODOLOGY:

Pancreatic cancer is most often diagnosed in adults aged 65 years or older. Providing cancer treatment for this older, often vulnerable, population comes with significant challenges and can lead to worse survival.

To examine real-world outcomes of older adults with untreated metastatic pancreatic cancer, researchers recruited patients aged 70 years or older and performed a geriatric assessment to identify comorbidities, cognitive issues, and other geriatric abnormalities.

Those who were deemed “fit” (ie, with no geriatric abnormalities) were assigned to receive off-study standard-of-care treatment, whereas those classified as “frail” (ie, with severe abnormalities) received off-study supportive care.

The remaining 176 “vulnerable” patients with mild to moderate geriatric abnormalities completed a geriatric and quality-of-life assessment and were then randomly assigned to receive either dose-reduced 5-fluorouracil (5-FU), leucovorin plus liposomal irinotecan (n = 88) or modified gemcitabine plus nab-paclitaxel (n = 88) every 2 weeks. Ultimately, 79 patients started the 5-FU combination and 75 received gemcitabine plus nab-paclitaxel. Patients were assessed every 8 weeks until disease progression or intolerance.

Overall, patients had a median age of 77 years; 61.9% were aged 75 years or older. About half were female, and 81.5% were White. The majority (87.5%) had a performance status of 0 or 1.

TAKEAWAY:

• Median overall survival was 4.7 months in the gemcitabine plus nab-paclitaxel arm and 4.4 months in the 5-FU combination group, with no significant survival difference observed between the two arms (P = .72).
• When the overall survival analysis was restricted to patients who received at least 4 weeks, or two cycles, of treatment (about 62% of patients), the median overall survival across the two treatment arms reached 8.0 months, in line with expectations for these regimens.
• Patient stratification revealed that those with a performance status of 2 had significantly worse overall survival than those with a status of 0: 1.4 months vs 6.9 months, respectively (hazard ratio [HR], 2.77; P < .001). A similar divide was seen when patients were stratified by physical/functional status and well-being. Age, however, did not significantly influence the results.
• Overall, more than half of patients experienced grade 3 or higher adverse events. Just over 38% of patients received only one to three cycles of therapy, whereas 26% remained on treatment for 12 or more cycles. The adverse event rates were similar between the two regimens, but the toxicity profile was slightly different — the researchers, for instance, observed more peripheral neuropathy with gemcitabine plus nab-paclitaxel and more diarrhea in the 5-FU combination arm.

IN PRACTICE:

• Overall, the “survival outcomes among vulnerable older patients were lower than expected, with high percentage of patients not able to start treatment, or complete one month of therapy due to clinical deterioration,” said study presenter Efrat Dotan, MD, chief, Division of Gastrointestinal Medical Oncology, Fox Chase Cancer Center, Philadelphia. 
• “For vulnerable older adults who can tolerate treatment, these two regimens provide clinicians with options for tailoring therapy based on toxicity profile,” Dr. Dotan added. But “tools are needed to better identify patients who can benefit from treatment.”
• The results underline the need to perform geriatric assessments, as opposed to merely looking at performance status, commented David F. Chang, PhD, MS, MBBS, professor of Surgical Oncology, University of Glasgow, Scotland, who was not involved in the study. 

SOURCE:

The research, presented at the 2024 annual meeting of the American Society of Clinical Oncology, was funded by the National Cancer Institute and the Eastern Cooperative Oncology Group.

LIMITATIONS:

Dr. Chang noted that the study did not reveal which treatment regimen was more effective.

DISCLOSURES:

Dr. Dotan declared relationships with Agenus, Amgen, G1 Therapeutics, Incyte, Olympus, and Taiho Pharmaceutical and institutional relationships with Dragonfly Therapeutics, Gilead Sciences, Ipsen, Kinnate Biopharma, Leap Therapeutics, Lilly, Lutris, NGM Biopharmaceuticals, Relay Therapeutics, and Zymeworks. Dr. Chang declared relationships with Immodulon Therapeutics and Mylan and institutional relationships with AstraZeneca, BMS GmbH & Co. KG, Immodulon Therapeutics, and Merck.

A version of this article appeared on Medscape.com.

LYON, FRANCE — High levels of lipoprotein(a) [Lp(a)] in the blood are associated with a significantly increased risk for chronic kidney disease, report investigators who are studying the link in a two-part study of more than 100,000 people.

There is already genetic evidence showing that Lp(a) can cause cardiovascular conditions, including myocardial infarction, aortic valve stenosis, peripheral artery disease, and ischemic stroke.

Now, researchers presenting at the European Atherosclerosis Society (EAS) 2024 Congress are adding new organs – the kidneys – to the list of those that can be damaged by elevated Lp(a).

“This is very important,” said lead investigator Anne Langsted, MD, PhD, DMSc, from the Department of Clinical Biochemistry at the Rigshospitalet in Denmark. And “hopefully, we’ll have a treatment for Lp(a) on the market very soon. Until then, I think individuals who have kidney disease would benefit a lot from reducing other risk factors, if they also have high levels” of Lp(a).

Using data gathered from the Copenhagen General Population Study, the study involved 108,439 individuals who had a range of tests including estimated glomerular filtration rate (eGFR), plasma Lp(a) levels, and LPA genotyping. The patients were then linked to a series of national registries to study outcomes. 

The researchers conducted two separate analyses: an observational study of Lp(a) levels in 70,040 individuals and a Mendelian randomization study of LPA kringle IV–type 2 domain repeats in 106,624 individuals. The number of those repeats is inversely associated with median Lp(a) plasma levels.

The observational study showed that eGFR decreased with increasing median plasma Lp(a) levels; the Mendelian randomization study indicated that eGFR decreased KIV-2 repeat numbers dropped.

Across both parts of the study, it was found that each 50 mg/dL increase in plasma Lp(a) levels was associated with an increased risk of at least 25% for chronic kidney disease.
 

Lp(a) and Chronic Kidney Disease

When high plasma levels of Lp(a) have been spotted before in patients with kidney disease, “we’ve kind of assumed that it was probably the kidney disease that caused the higher levels,” Dr. Langsted said. But her team hypothesized that the opposite was at play and that Lp(a) levels are genetically determined, and increased plasma Lp(a) levels may be causally associated with rising risk for chronic kidney disease.

Gerald F. Watts, MD, PhD, DSc, Winthrop Professor of cardiometabolic and internal medicine at the University of Western Australia in Perth, and co-chair of the study, said in an interview that “although Mendelian randomization is a technique that allows you to infer causality, it’s probably a little bit more complex than that in reality,” adding that there is likely a bidirectional relationship between Lp(a) and chronic kidney disease.

Having increased Lp(a) levels on their own is not sufficient to trigger chronic kidney disease. “You probably need another event and then you get into a vicious cycle,” Dr. Watts said.

The mechanism linking Lp(a) with chronic kidney disease remains unclear, but Dr. Watts explained that the lipoprotein probably damages the renal tubes when it is reabsorbed after it dissociates from low-density lipoprotein cholesterol.

The next step will be to identify the people who are most susceptible to this and figure out what treatment might help. Dr. Watts suggested that gene silencing, in which Lp(a) is “completely obliterated,” will lead to an improvement in renal function.

A version of this article appeared on Medscape.com.

LYON, FRANCE — High levels of lipoprotein(a) [Lp(a)] in the blood are associated with a significantly increased risk for chronic kidney disease, report investigators who are studying the link in a two-part study of more than 100,000 people.

There is already genetic evidence showing that Lp(a) can cause cardiovascular conditions, including myocardial infarction, aortic valve stenosis, peripheral artery disease, and ischemic stroke.

Now, researchers presenting at the European Atherosclerosis Society (EAS) 2024 Congress are adding new organs – the kidneys – to the list of those that can be damaged by elevated Lp(a).

“This is very important,” said lead investigator Anne Langsted, MD, PhD, DMSc, from the Department of Clinical Biochemistry at the Rigshospitalet in Denmark. And “hopefully, we’ll have a treatment for Lp(a) on the market very soon. Until then, I think individuals who have kidney disease would benefit a lot from reducing other risk factors, if they also have high levels” of Lp(a).

Using data gathered from the Copenhagen General Population Study, the study involved 108,439 individuals who had a range of tests including estimated glomerular filtration rate (eGFR), plasma Lp(a) levels, and LPA genotyping. The patients were then linked to a series of national registries to study outcomes. 

The researchers conducted two separate analyses: an observational study of Lp(a) levels in 70,040 individuals and a Mendelian randomization study of LPA kringle IV–type 2 domain repeats in 106,624 individuals. The number of those repeats is inversely associated with median Lp(a) plasma levels.

The observational study showed that eGFR decreased with increasing median plasma Lp(a) levels; the Mendelian randomization study indicated that eGFR decreased KIV-2 repeat numbers dropped.

Across both parts of the study, it was found that each 50 mg/dL increase in plasma Lp(a) levels was associated with an increased risk of at least 25% for chronic kidney disease.
 

Lp(a) and Chronic Kidney Disease

When high plasma levels of Lp(a) have been spotted before in patients with kidney disease, “we’ve kind of assumed that it was probably the kidney disease that caused the higher levels,” Dr. Langsted said. But her team hypothesized that the opposite was at play and that Lp(a) levels are genetically determined, and increased plasma Lp(a) levels may be causally associated with rising risk for chronic kidney disease.

Gerald F. Watts, MD, PhD, DSc, Winthrop Professor of cardiometabolic and internal medicine at the University of Western Australia in Perth, and co-chair of the study, said in an interview that “although Mendelian randomization is a technique that allows you to infer causality, it’s probably a little bit more complex than that in reality,” adding that there is likely a bidirectional relationship between Lp(a) and chronic kidney disease.

Having increased Lp(a) levels on their own is not sufficient to trigger chronic kidney disease. “You probably need another event and then you get into a vicious cycle,” Dr. Watts said.

The mechanism linking Lp(a) with chronic kidney disease remains unclear, but Dr. Watts explained that the lipoprotein probably damages the renal tubes when it is reabsorbed after it dissociates from low-density lipoprotein cholesterol.

The next step will be to identify the people who are most susceptible to this and figure out what treatment might help. Dr. Watts suggested that gene silencing, in which Lp(a) is “completely obliterated,” will lead to an improvement in renal function.

A version of this article appeared on Medscape.com.

LYON, FRANCE — High levels of lipoprotein(a) [Lp(a)] in the blood are associated with a significantly increased risk for chronic kidney disease, report investigators who are studying the link in a two-part study of more than 100,000 people.

There is already genetic evidence showing that Lp(a) can cause cardiovascular conditions, including myocardial infarction, aortic valve stenosis, peripheral artery disease, and ischemic stroke.

Now, researchers presenting at the European Atherosclerosis Society (EAS) 2024 Congress are adding new organs – the kidneys – to the list of those that can be damaged by elevated Lp(a).

“This is very important,” said lead investigator Anne Langsted, MD, PhD, DMSc, from the Department of Clinical Biochemistry at the Rigshospitalet in Denmark. And “hopefully, we’ll have a treatment for Lp(a) on the market very soon. Until then, I think individuals who have kidney disease would benefit a lot from reducing other risk factors, if they also have high levels” of Lp(a).

Using data gathered from the Copenhagen General Population Study, the study involved 108,439 individuals who had a range of tests including estimated glomerular filtration rate (eGFR), plasma Lp(a) levels, and LPA genotyping. The patients were then linked to a series of national registries to study outcomes. 

The researchers conducted two separate analyses: an observational study of Lp(a) levels in 70,040 individuals and a Mendelian randomization study of LPA kringle IV–type 2 domain repeats in 106,624 individuals. The number of those repeats is inversely associated with median Lp(a) plasma levels.

The observational study showed that eGFR decreased with increasing median plasma Lp(a) levels; the Mendelian randomization study indicated that eGFR decreased KIV-2 repeat numbers dropped.

Across both parts of the study, it was found that each 50 mg/dL increase in plasma Lp(a) levels was associated with an increased risk of at least 25% for chronic kidney disease.
 

Lp(a) and Chronic Kidney Disease

When high plasma levels of Lp(a) have been spotted before in patients with kidney disease, “we’ve kind of assumed that it was probably the kidney disease that caused the higher levels,” Dr. Langsted said. But her team hypothesized that the opposite was at play and that Lp(a) levels are genetically determined, and increased plasma Lp(a) levels may be causally associated with rising risk for chronic kidney disease.

Gerald F. Watts, MD, PhD, DSc, Winthrop Professor of cardiometabolic and internal medicine at the University of Western Australia in Perth, and co-chair of the study, said in an interview that “although Mendelian randomization is a technique that allows you to infer causality, it’s probably a little bit more complex than that in reality,” adding that there is likely a bidirectional relationship between Lp(a) and chronic kidney disease.

Having increased Lp(a) levels on their own is not sufficient to trigger chronic kidney disease. “You probably need another event and then you get into a vicious cycle,” Dr. Watts said.

The mechanism linking Lp(a) with chronic kidney disease remains unclear, but Dr. Watts explained that the lipoprotein probably damages the renal tubes when it is reabsorbed after it dissociates from low-density lipoprotein cholesterol.

The next step will be to identify the people who are most susceptible to this and figure out what treatment might help. Dr. Watts suggested that gene silencing, in which Lp(a) is “completely obliterated,” will lead to an improvement in renal function.

A version of this article appeared on Medscape.com.

Over the past few years, several new, highly effective treatment strategies have improved survival outcomes in patients with early breast cancer.

“We’ve been very fortunate” to see these advances, Sara M. Tolaney, MD, MPH, chief, Division of Breast Oncology, Dana-Farber Cancer Institute, Boston, told attendees at the European Society of Medical Oncology (ESMO) Breast Cancer annual congress.

However, Dr. Tolaney noted, these new treatment approaches can come with big limitations — namely, potential overtreatment of some patients as well as short- and long-term toxicities, some of which can be life-threatening.

These caveats have prompted trials exploring strategies to de-escalate therapy, which essentially means providing the right amount of treatment to the right patient at the right time, said Dr. Tolaney. The goal is to “right-size” or “optimize therapy” to maintain strong outcomes while mitigating side effects.

De-escalation studies are “critical to preserving quality of life” and affect the cost-effectiveness of therapy, she explained.

But, she added, de-escalation trials are “not a very attractive strategy to pharmaceutical companies” and can be challenging for researchers to conduct. These trials may, for instance, lack adequate sample sizes and sufficient statistical power, which can interfere with achieving clinically meaningful findings that may affect practice.

That is why carefully designing de-escalation trials is crucial, Dr. Tolaney said.

In her talk at ESMO Breast, Dr. Tolaney highlighted several strategies for designing these trials.

One strategy is to shorten the duration of therapy, said Dr. Tolaney.

This approach was explored in the PHARE and PERSEPHONE trials, which looked at 6 vs 12 months of trastuzumab in nonmetastatic breast cancer. Other trials, such as GeparNuevo and KEYNOTE-522, explored whether adjuvant checkpoint inhibitor therapy was needed, or could be skipped, following neoadjuvant therapy. This approach requires establishing noninferiority, or similar efficacy, between the standard of care and the shorter duration of therapy.

A second strategy is to remove part of the chemotherapy regimen, typically the most toxic agent, Dr. Tolaney continued.

Conducting a prospective, randomized trial exploring this approach in human epidermal growth factor receptor 2–positive (HER2+) early breast cancer, for example, would be difficult for a range of reasons, such as the need to enroll thousands of patients.

Dr. Tolaney and colleagues, however, designed a nonrandomized prospective study — the APT trial — with just over 400 patients to assess adjuvant paclitaxel plus trastuzumab in patients with node-negative HER2+ disease. The open-label, single-arm, phase 2 APT trial found that adjuvant paclitaxel and trastuzumab led to a 10-year recurrence-free interval of 96.3%, 10-year overall survival of 94.3%, and 10-year breast cancer–specific survival of 98.8%.

Outcomes with this adjuvant regimen were comparable to previous findings in historical controls who received doxorubicin, cyclophosphamide, paclitaxel, and trastuzumab or docetaxel, carboplatin, and trastuzumab.

Dr. Tolaney concluded that given few events, “it’s unlikely we need to escalate therapy to do better for most patients,” and the APT regimen “can be considered a reasonable and appealing approach for the majority of patients” with node-negative HER2+ breast cancer.

“A single-arm design for a de-escalation study can be practice-changing but only if there are very few recurrences,” Dr. Tolaney said.

Substituting chemotherapy with a targeted, potentially less-toxic agent is a third de-escalation approach. The ATEMPT trial compared patients receiving trastuzumab emtansine (T-DM1) with those receiving paclitaxel plus trastuzumab followed by maintenance trastuzumab.

Investigators found that de-escalation with T-DM1 was associated with very few recurrences but similar rates of certain adverse events, including grade 2 or higher neurotoxicity, febrile neutropenia, and grade 4 or higher hematologic toxicity.

However, there are questions about how to define “less toxic,” Dr. Tolaney said. The trial found, for instance, that T-DM1 did have some advantages — patients reported better quality of life and experienced less alopecia and neurotoxicity, as well as a less severe impact on fertility.

Understanding the right endpoint to demonstrate less toxicity is critical, “as we start to think about how to replace standard chemotherapies with better targeted drugs,” she added.

The ATEMPT 2.0 trial, which is currently enrolling, will aim to answer some of these questions about defining and demonstrating less toxicity, she said.

Finally, some researchers are attempting to omit chemotherapy altogether with the help of biomarkers. The TAILORx trial, for instance, aimed to stratify patients with early-stage breast cancer by clinical risk factors combined with a 21-gene expression assay and found that adjuvant chemotherapy was not necessary in a large proportion of these women.

On the biomarker front, oncologists might be able to use ctDNA to guide decision-making and personalize therapy, Tolaney said. The presence of ctDNA is associated with an almost 100% likelihood of having a recurrence, whereas its absence suggests better outcomes, she explained.

Oncologists could use the presence or absence of ctDNA to guide next steps — assign patients to follow-up assessments when ctDNA is not present or to standard or experimental treatment when it is present. It may also be possible to leverage the presence of minimal residual disease to help direct treatment choices.

But ctDNA is currently not as perfect a predictor of outcome as it could be, she cautioned. “We need more sensitive assays [so] I’m not sure we’re quite ready to use lack of ctDNA to de-escalate treatment,” she said.

Dr. Tolaney declared relationships with Novartis, Pfizer, Merck, Lilly, AstraZeneca, Genentech/Roche, Eisai, Sanofi, Bristol Myers Squib, and other companies.

A version of this article appeared on Medscape.com .

Over the past few years, several new, highly effective treatment strategies have improved survival outcomes in patients with early breast cancer.

“We’ve been very fortunate” to see these advances, Sara M. Tolaney, MD, MPH, chief, Division of Breast Oncology, Dana-Farber Cancer Institute, Boston, told attendees at the European Society of Medical Oncology (ESMO) Breast Cancer annual congress.

However, Dr. Tolaney noted, these new treatment approaches can come with big limitations — namely, potential overtreatment of some patients as well as short- and long-term toxicities, some of which can be life-threatening.

These caveats have prompted trials exploring strategies to de-escalate therapy, which essentially means providing the right amount of treatment to the right patient at the right time, said Dr. Tolaney. The goal is to “right-size” or “optimize therapy” to maintain strong outcomes while mitigating side effects.

De-escalation studies are “critical to preserving quality of life” and affect the cost-effectiveness of therapy, she explained.

But, she added, de-escalation trials are “not a very attractive strategy to pharmaceutical companies” and can be challenging for researchers to conduct. These trials may, for instance, lack adequate sample sizes and sufficient statistical power, which can interfere with achieving clinically meaningful findings that may affect practice.

That is why carefully designing de-escalation trials is crucial, Dr. Tolaney said.

In her talk at ESMO Breast, Dr. Tolaney highlighted several strategies for designing these trials.

One strategy is to shorten the duration of therapy, said Dr. Tolaney.

This approach was explored in the PHARE and PERSEPHONE trials, which looked at 6 vs 12 months of trastuzumab in nonmetastatic breast cancer. Other trials, such as GeparNuevo and KEYNOTE-522, explored whether adjuvant checkpoint inhibitor therapy was needed, or could be skipped, following neoadjuvant therapy. This approach requires establishing noninferiority, or similar efficacy, between the standard of care and the shorter duration of therapy.

A second strategy is to remove part of the chemotherapy regimen, typically the most toxic agent, Dr. Tolaney continued.

Conducting a prospective, randomized trial exploring this approach in human epidermal growth factor receptor 2–positive (HER2+) early breast cancer, for example, would be difficult for a range of reasons, such as the need to enroll thousands of patients.

Dr. Tolaney and colleagues, however, designed a nonrandomized prospective study — the APT trial — with just over 400 patients to assess adjuvant paclitaxel plus trastuzumab in patients with node-negative HER2+ disease. The open-label, single-arm, phase 2 APT trial found that adjuvant paclitaxel and trastuzumab led to a 10-year recurrence-free interval of 96.3%, 10-year overall survival of 94.3%, and 10-year breast cancer–specific survival of 98.8%.

Outcomes with this adjuvant regimen were comparable to previous findings in historical controls who received doxorubicin, cyclophosphamide, paclitaxel, and trastuzumab or docetaxel, carboplatin, and trastuzumab.

Dr. Tolaney concluded that given few events, “it’s unlikely we need to escalate therapy to do better for most patients,” and the APT regimen “can be considered a reasonable and appealing approach for the majority of patients” with node-negative HER2+ breast cancer.

“A single-arm design for a de-escalation study can be practice-changing but only if there are very few recurrences,” Dr. Tolaney said.

Substituting chemotherapy with a targeted, potentially less-toxic agent is a third de-escalation approach. The ATEMPT trial compared patients receiving trastuzumab emtansine (T-DM1) with those receiving paclitaxel plus trastuzumab followed by maintenance trastuzumab.

Investigators found that de-escalation with T-DM1 was associated with very few recurrences but similar rates of certain adverse events, including grade 2 or higher neurotoxicity, febrile neutropenia, and grade 4 or higher hematologic toxicity.

However, there are questions about how to define “less toxic,” Dr. Tolaney said. The trial found, for instance, that T-DM1 did have some advantages — patients reported better quality of life and experienced less alopecia and neurotoxicity, as well as a less severe impact on fertility.

Understanding the right endpoint to demonstrate less toxicity is critical, “as we start to think about how to replace standard chemotherapies with better targeted drugs,” she added.

The ATEMPT 2.0 trial, which is currently enrolling, will aim to answer some of these questions about defining and demonstrating less toxicity, she said.

Finally, some researchers are attempting to omit chemotherapy altogether with the help of biomarkers. The TAILORx trial, for instance, aimed to stratify patients with early-stage breast cancer by clinical risk factors combined with a 21-gene expression assay and found that adjuvant chemotherapy was not necessary in a large proportion of these women.

On the biomarker front, oncologists might be able to use ctDNA to guide decision-making and personalize therapy, Tolaney said. The presence of ctDNA is associated with an almost 100% likelihood of having a recurrence, whereas its absence suggests better outcomes, she explained.

Oncologists could use the presence or absence of ctDNA to guide next steps — assign patients to follow-up assessments when ctDNA is not present or to standard or experimental treatment when it is present. It may also be possible to leverage the presence of minimal residual disease to help direct treatment choices.

But ctDNA is currently not as perfect a predictor of outcome as it could be, she cautioned. “We need more sensitive assays [so] I’m not sure we’re quite ready to use lack of ctDNA to de-escalate treatment,” she said.

Dr. Tolaney declared relationships with Novartis, Pfizer, Merck, Lilly, AstraZeneca, Genentech/Roche, Eisai, Sanofi, Bristol Myers Squib, and other companies.

A version of this article appeared on Medscape.com .

Over the past few years, several new, highly effective treatment strategies have improved survival outcomes in patients with early breast cancer.

“We’ve been very fortunate” to see these advances, Sara M. Tolaney, MD, MPH, chief, Division of Breast Oncology, Dana-Farber Cancer Institute, Boston, told attendees at the European Society of Medical Oncology (ESMO) Breast Cancer annual congress.

However, Dr. Tolaney noted, these new treatment approaches can come with big limitations — namely, potential overtreatment of some patients as well as short- and long-term toxicities, some of which can be life-threatening.

These caveats have prompted trials exploring strategies to de-escalate therapy, which essentially means providing the right amount of treatment to the right patient at the right time, said Dr. Tolaney. The goal is to “right-size” or “optimize therapy” to maintain strong outcomes while mitigating side effects.

De-escalation studies are “critical to preserving quality of life” and affect the cost-effectiveness of therapy, she explained.

But, she added, de-escalation trials are “not a very attractive strategy to pharmaceutical companies” and can be challenging for researchers to conduct. These trials may, for instance, lack adequate sample sizes and sufficient statistical power, which can interfere with achieving clinically meaningful findings that may affect practice.

That is why carefully designing de-escalation trials is crucial, Dr. Tolaney said.

In her talk at ESMO Breast, Dr. Tolaney highlighted several strategies for designing these trials.

One strategy is to shorten the duration of therapy, said Dr. Tolaney.

This approach was explored in the PHARE and PERSEPHONE trials, which looked at 6 vs 12 months of trastuzumab in nonmetastatic breast cancer. Other trials, such as GeparNuevo and KEYNOTE-522, explored whether adjuvant checkpoint inhibitor therapy was needed, or could be skipped, following neoadjuvant therapy. This approach requires establishing noninferiority, or similar efficacy, between the standard of care and the shorter duration of therapy.

A second strategy is to remove part of the chemotherapy regimen, typically the most toxic agent, Dr. Tolaney continued.

Conducting a prospective, randomized trial exploring this approach in human epidermal growth factor receptor 2–positive (HER2+) early breast cancer, for example, would be difficult for a range of reasons, such as the need to enroll thousands of patients.

Dr. Tolaney and colleagues, however, designed a nonrandomized prospective study — the APT trial — with just over 400 patients to assess adjuvant paclitaxel plus trastuzumab in patients with node-negative HER2+ disease. The open-label, single-arm, phase 2 APT trial found that adjuvant paclitaxel and trastuzumab led to a 10-year recurrence-free interval of 96.3%, 10-year overall survival of 94.3%, and 10-year breast cancer–specific survival of 98.8%.

Outcomes with this adjuvant regimen were comparable to previous findings in historical controls who received doxorubicin, cyclophosphamide, paclitaxel, and trastuzumab or docetaxel, carboplatin, and trastuzumab.

Dr. Tolaney concluded that given few events, “it’s unlikely we need to escalate therapy to do better for most patients,” and the APT regimen “can be considered a reasonable and appealing approach for the majority of patients” with node-negative HER2+ breast cancer.

“A single-arm design for a de-escalation study can be practice-changing but only if there are very few recurrences,” Dr. Tolaney said.

Substituting chemotherapy with a targeted, potentially less-toxic agent is a third de-escalation approach. The ATEMPT trial compared patients receiving trastuzumab emtansine (T-DM1) with those receiving paclitaxel plus trastuzumab followed by maintenance trastuzumab.

Investigators found that de-escalation with T-DM1 was associated with very few recurrences but similar rates of certain adverse events, including grade 2 or higher neurotoxicity, febrile neutropenia, and grade 4 or higher hematologic toxicity.

However, there are questions about how to define “less toxic,” Dr. Tolaney said. The trial found, for instance, that T-DM1 did have some advantages — patients reported better quality of life and experienced less alopecia and neurotoxicity, as well as a less severe impact on fertility.

Understanding the right endpoint to demonstrate less toxicity is critical, “as we start to think about how to replace standard chemotherapies with better targeted drugs,” she added.

The ATEMPT 2.0 trial, which is currently enrolling, will aim to answer some of these questions about defining and demonstrating less toxicity, she said.

Finally, some researchers are attempting to omit chemotherapy altogether with the help of biomarkers. The TAILORx trial, for instance, aimed to stratify patients with early-stage breast cancer by clinical risk factors combined with a 21-gene expression assay and found that adjuvant chemotherapy was not necessary in a large proportion of these women.

On the biomarker front, oncologists might be able to use ctDNA to guide decision-making and personalize therapy, Tolaney said. The presence of ctDNA is associated with an almost 100% likelihood of having a recurrence, whereas its absence suggests better outcomes, she explained.

Oncologists could use the presence or absence of ctDNA to guide next steps — assign patients to follow-up assessments when ctDNA is not present or to standard or experimental treatment when it is present. It may also be possible to leverage the presence of minimal residual disease to help direct treatment choices.

But ctDNA is currently not as perfect a predictor of outcome as it could be, she cautioned. “We need more sensitive assays [so] I’m not sure we’re quite ready to use lack of ctDNA to de-escalate treatment,” she said.

Dr. Tolaney declared relationships with Novartis, Pfizer, Merck, Lilly, AstraZeneca, Genentech/Roche, Eisai, Sanofi, Bristol Myers Squib, and other companies.

A version of this article appeared on Medscape.com .

Adding atezolizumab to chemotherapy in patients with anti–programmed death ligand 1 (PD-L1)–positive triple-negative breast cancer (TNBC) who have relapsed within 12 months of their last curative treatment does not improve their survival, results of the IMpassion132 trial show.

Our results “highlight the importance of recognizing TNBC heterogeneity, especially in the first-line setting” said Rebecca A. Dent, MD, MSc, National Cancer Center Singapore and Duke-NUS Medical School, Singapore, who presented the study at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.

“These patients have a dismal prognosis and represent a high unmet need,” she added. 

The current findings follow those from the IMpassion130 trial, which showed that the combination of atezolizumab with nab-paclitaxel chemotherapy offered no survival benefit in previously untreated locally advanced or metastatic TNBC despite a progression-free survival benefit on interim analysis.

Rapidly relapsing TNBC “represents one of most challenging clinical situations” because it is aggressive and “intrinsically resistant to standard therapies,” said Dr. Dent. It is also more common in younger patients with large primary tumors and no BRCA alterations.

“Most importantly, however, is that most trials actually exclude these patients,” she noted, “posing a real challenge for us in clinical practice.”

IMpassion132 enrolled 594 patients with unresectable locally advanced or metastatic TNBC who had experienced disease progression more than 12 months after their last treatment for early TNBC with curative intent.

Patients had received prior anthracycline and taxane therapy for but no prior chemotherapy for advanced disease.

Study participants were randomly assigned to chemotherapy with carboplatin-gemcitabine or capecitabine plus atezolizumab or placebo, with treatment continued until disease progression or unacceptable toxicity. The primary endpoint was overall survival.

Initially, all patients with TNBC who met the study criteria were enrolled in the randomized, phase 3, double-blinded trial; however, the trial was then amended to include only PD-L1–positive patients after the results of IMpassion130 “clearly showed us that the benefits of immune checkpoint inhibition were largely driven by those patients,” Dr. Dent explained.

The 354 patients with PD-L1–positive disease were “young,” she added, with a median age of 48 years. The youngest was 23 years old.

The majority (66%-69%) had a disease-free interval of less than 6 months after treatment with curative intent. Lung and/or liver metastases were present in 60%-62% of patients, and 18% had previously received platinum-based chemotherapy.

After a median follow-up of 9.8 months, overall survival was a median of 12.1 months in the atezolizumab group vs 11.2 months with placebo, at a hazard ratio of 0.93 (P = .59).

A similar result was seen when looking at the modified intention-to-treat population, and when stratifying the patients by prespecified subgroup.

Dr. Dent pointed out that in the placebo group, patients treated with capecitabine had a median overall survival of 12.6 months vs 9.9 months in those given carboplatin-gemcitabine , which she described as “hypothesis generating” because “prior therapy may trigger a variety of resistance mechanisms.”

The disease-free interval also seemed to play a role in the placebo group. Patients who had a disease-free interval of 6 or more months prior to study enrollment had a median overall survival of 12.8 months vs 9.4 months in those with an interval of less than 6 months.

There were no significant differences in progression-free survival or duration of overall response between the atezolizumab and placebo groups.

“In terms of the safety data, clearly we’re getting better at identifying immune checkpoint inhibition toxicities and initiating therapies for these toxicities earlier,” Dr. Dent said, because there were “no new safety signals.”

The rate of treatment-related grade 3 or 4 adverse events was similar between patients given atezolizumab and those assigned to placebo, at 65% vs 62%. Rates of grade 5 events were identical, at 1%.

Commenting on the study, Sara M. Tolaney, MD, MPH, chief, Division of Breast Oncology, Susan F. Smith Center for Women’s Cancers, Dana-Farber Cancer Institute, Boston, questioned the role for immunotherapy in patients with TNBC who experience early relapse. 

This is not the first trial to fail to show a benefit in this space, she said. Collectively, these results make “me think that these tumors are pretty immunologically cold, making them less likely to benefit from checkpoint inhibition.” 

The patients that do relapse, “have highly treatment refractory disease,” and “we need to think about other novel therapeutic strategies for this population,” she told this news organization.

IMpassion132 nevertheless represents a “unique opportunity to better understand the biology of these rapidly relapsing tumors, and hopefully use this information to develop more novel treatment approaches for this population,” she said.

“That being said, I do think that this is going to become an even more challenging area,” Dr. Tolaney said. “In the modern era, these patients are receiving multi-agent chemotherapy with preoperative checkpoint inhibition, and many then go on to receive additional systemic treatment in the adjuvant setting.”

The study was sponsored by Hoffmann-La Roche.

Dr. Dent declares relationships with AstraZeneca, Roche, Eisai, Lilly, MSD, Novartis, and Pfizer. Dr. Tolaney declares relationships with Novartis, Pfizer, Merck, Lilly, AstraZeneca, Genentech/Roche, Eisai, Sanofi, Bristol Myers Squib, Seattle Genetics, CytomX Therapeutics, Daiichi Sankyo, Gilead, Ellipses Pharma, 4D Pharma, OncoSec Medical Inc, BeyondSpring Pharmaceuticals, OncXerna, Zymeworks, Zentalis, Blueprint Medicines, Reveal Genomics, ARC Therapeutics, Myovant, Zetagen, Umoja Biopharma, Menarini/Stemline, Aadi Biopharma, Bayer, Jazz Pharmaceuticals, Exelixis, Novartis, Nanonstring, and Cyclacel.

A version of this article appeared on Medscape.com .

Adding atezolizumab to chemotherapy in patients with anti–programmed death ligand 1 (PD-L1)–positive triple-negative breast cancer (TNBC) who have relapsed within 12 months of their last curative treatment does not improve their survival, results of the IMpassion132 trial show.

Our results “highlight the importance of recognizing TNBC heterogeneity, especially in the first-line setting” said Rebecca A. Dent, MD, MSc, National Cancer Center Singapore and Duke-NUS Medical School, Singapore, who presented the study at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.

“These patients have a dismal prognosis and represent a high unmet need,” she added. 

The current findings follow those from the IMpassion130 trial, which showed that the combination of atezolizumab with nab-paclitaxel chemotherapy offered no survival benefit in previously untreated locally advanced or metastatic TNBC despite a progression-free survival benefit on interim analysis.

Rapidly relapsing TNBC “represents one of most challenging clinical situations” because it is aggressive and “intrinsically resistant to standard therapies,” said Dr. Dent. It is also more common in younger patients with large primary tumors and no BRCA alterations.

“Most importantly, however, is that most trials actually exclude these patients,” she noted, “posing a real challenge for us in clinical practice.”

IMpassion132 enrolled 594 patients with unresectable locally advanced or metastatic TNBC who had experienced disease progression more than 12 months after their last treatment for early TNBC with curative intent.

Patients had received prior anthracycline and taxane therapy for but no prior chemotherapy for advanced disease.

Study participants were randomly assigned to chemotherapy with carboplatin-gemcitabine or capecitabine plus atezolizumab or placebo, with treatment continued until disease progression or unacceptable toxicity. The primary endpoint was overall survival.

Initially, all patients with TNBC who met the study criteria were enrolled in the randomized, phase 3, double-blinded trial; however, the trial was then amended to include only PD-L1–positive patients after the results of IMpassion130 “clearly showed us that the benefits of immune checkpoint inhibition were largely driven by those patients,” Dr. Dent explained.

The 354 patients with PD-L1–positive disease were “young,” she added, with a median age of 48 years. The youngest was 23 years old.

The majority (66%-69%) had a disease-free interval of less than 6 months after treatment with curative intent. Lung and/or liver metastases were present in 60%-62% of patients, and 18% had previously received platinum-based chemotherapy.

After a median follow-up of 9.8 months, overall survival was a median of 12.1 months in the atezolizumab group vs 11.2 months with placebo, at a hazard ratio of 0.93 (P = .59).

A similar result was seen when looking at the modified intention-to-treat population, and when stratifying the patients by prespecified subgroup.

Dr. Dent pointed out that in the placebo group, patients treated with capecitabine had a median overall survival of 12.6 months vs 9.9 months in those given carboplatin-gemcitabine , which she described as “hypothesis generating” because “prior therapy may trigger a variety of resistance mechanisms.”

The disease-free interval also seemed to play a role in the placebo group. Patients who had a disease-free interval of 6 or more months prior to study enrollment had a median overall survival of 12.8 months vs 9.4 months in those with an interval of less than 6 months.

There were no significant differences in progression-free survival or duration of overall response between the atezolizumab and placebo groups.

“In terms of the safety data, clearly we’re getting better at identifying immune checkpoint inhibition toxicities and initiating therapies for these toxicities earlier,” Dr. Dent said, because there were “no new safety signals.”

The rate of treatment-related grade 3 or 4 adverse events was similar between patients given atezolizumab and those assigned to placebo, at 65% vs 62%. Rates of grade 5 events were identical, at 1%.

Commenting on the study, Sara M. Tolaney, MD, MPH, chief, Division of Breast Oncology, Susan F. Smith Center for Women’s Cancers, Dana-Farber Cancer Institute, Boston, questioned the role for immunotherapy in patients with TNBC who experience early relapse. 

This is not the first trial to fail to show a benefit in this space, she said. Collectively, these results make “me think that these tumors are pretty immunologically cold, making them less likely to benefit from checkpoint inhibition.” 

The patients that do relapse, “have highly treatment refractory disease,” and “we need to think about other novel therapeutic strategies for this population,” she told this news organization.

IMpassion132 nevertheless represents a “unique opportunity to better understand the biology of these rapidly relapsing tumors, and hopefully use this information to develop more novel treatment approaches for this population,” she said.

“That being said, I do think that this is going to become an even more challenging area,” Dr. Tolaney said. “In the modern era, these patients are receiving multi-agent chemotherapy with preoperative checkpoint inhibition, and many then go on to receive additional systemic treatment in the adjuvant setting.”

The study was sponsored by Hoffmann-La Roche.

Dr. Dent declares relationships with AstraZeneca, Roche, Eisai, Lilly, MSD, Novartis, and Pfizer. Dr. Tolaney declares relationships with Novartis, Pfizer, Merck, Lilly, AstraZeneca, Genentech/Roche, Eisai, Sanofi, Bristol Myers Squib, Seattle Genetics, CytomX Therapeutics, Daiichi Sankyo, Gilead, Ellipses Pharma, 4D Pharma, OncoSec Medical Inc, BeyondSpring Pharmaceuticals, OncXerna, Zymeworks, Zentalis, Blueprint Medicines, Reveal Genomics, ARC Therapeutics, Myovant, Zetagen, Umoja Biopharma, Menarini/Stemline, Aadi Biopharma, Bayer, Jazz Pharmaceuticals, Exelixis, Novartis, Nanonstring, and Cyclacel.

A version of this article appeared on Medscape.com .

Adding atezolizumab to chemotherapy in patients with anti–programmed death ligand 1 (PD-L1)–positive triple-negative breast cancer (TNBC) who have relapsed within 12 months of their last curative treatment does not improve their survival, results of the IMpassion132 trial show.

Our results “highlight the importance of recognizing TNBC heterogeneity, especially in the first-line setting” said Rebecca A. Dent, MD, MSc, National Cancer Center Singapore and Duke-NUS Medical School, Singapore, who presented the study at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.

“These patients have a dismal prognosis and represent a high unmet need,” she added. 

The current findings follow those from the IMpassion130 trial, which showed that the combination of atezolizumab with nab-paclitaxel chemotherapy offered no survival benefit in previously untreated locally advanced or metastatic TNBC despite a progression-free survival benefit on interim analysis.

Rapidly relapsing TNBC “represents one of most challenging clinical situations” because it is aggressive and “intrinsically resistant to standard therapies,” said Dr. Dent. It is also more common in younger patients with large primary tumors and no BRCA alterations.

“Most importantly, however, is that most trials actually exclude these patients,” she noted, “posing a real challenge for us in clinical practice.”

IMpassion132 enrolled 594 patients with unresectable locally advanced or metastatic TNBC who had experienced disease progression more than 12 months after their last treatment for early TNBC with curative intent.

Patients had received prior anthracycline and taxane therapy for but no prior chemotherapy for advanced disease.

Study participants were randomly assigned to chemotherapy with carboplatin-gemcitabine or capecitabine plus atezolizumab or placebo, with treatment continued until disease progression or unacceptable toxicity. The primary endpoint was overall survival.

Initially, all patients with TNBC who met the study criteria were enrolled in the randomized, phase 3, double-blinded trial; however, the trial was then amended to include only PD-L1–positive patients after the results of IMpassion130 “clearly showed us that the benefits of immune checkpoint inhibition were largely driven by those patients,” Dr. Dent explained.

The 354 patients with PD-L1–positive disease were “young,” she added, with a median age of 48 years. The youngest was 23 years old.

The majority (66%-69%) had a disease-free interval of less than 6 months after treatment with curative intent. Lung and/or liver metastases were present in 60%-62% of patients, and 18% had previously received platinum-based chemotherapy.

After a median follow-up of 9.8 months, overall survival was a median of 12.1 months in the atezolizumab group vs 11.2 months with placebo, at a hazard ratio of 0.93 (P = .59).

A similar result was seen when looking at the modified intention-to-treat population, and when stratifying the patients by prespecified subgroup.

Dr. Dent pointed out that in the placebo group, patients treated with capecitabine had a median overall survival of 12.6 months vs 9.9 months in those given carboplatin-gemcitabine , which she described as “hypothesis generating” because “prior therapy may trigger a variety of resistance mechanisms.”

The disease-free interval also seemed to play a role in the placebo group. Patients who had a disease-free interval of 6 or more months prior to study enrollment had a median overall survival of 12.8 months vs 9.4 months in those with an interval of less than 6 months.

There were no significant differences in progression-free survival or duration of overall response between the atezolizumab and placebo groups.

“In terms of the safety data, clearly we’re getting better at identifying immune checkpoint inhibition toxicities and initiating therapies for these toxicities earlier,” Dr. Dent said, because there were “no new safety signals.”

The rate of treatment-related grade 3 or 4 adverse events was similar between patients given atezolizumab and those assigned to placebo, at 65% vs 62%. Rates of grade 5 events were identical, at 1%.

Commenting on the study, Sara M. Tolaney, MD, MPH, chief, Division of Breast Oncology, Susan F. Smith Center for Women’s Cancers, Dana-Farber Cancer Institute, Boston, questioned the role for immunotherapy in patients with TNBC who experience early relapse. 

This is not the first trial to fail to show a benefit in this space, she said. Collectively, these results make “me think that these tumors are pretty immunologically cold, making them less likely to benefit from checkpoint inhibition.” 

The patients that do relapse, “have highly treatment refractory disease,” and “we need to think about other novel therapeutic strategies for this population,” she told this news organization.

IMpassion132 nevertheless represents a “unique opportunity to better understand the biology of these rapidly relapsing tumors, and hopefully use this information to develop more novel treatment approaches for this population,” she said.

“That being said, I do think that this is going to become an even more challenging area,” Dr. Tolaney said. “In the modern era, these patients are receiving multi-agent chemotherapy with preoperative checkpoint inhibition, and many then go on to receive additional systemic treatment in the adjuvant setting.”

The study was sponsored by Hoffmann-La Roche.

Dr. Dent declares relationships with AstraZeneca, Roche, Eisai, Lilly, MSD, Novartis, and Pfizer. Dr. Tolaney declares relationships with Novartis, Pfizer, Merck, Lilly, AstraZeneca, Genentech/Roche, Eisai, Sanofi, Bristol Myers Squib, Seattle Genetics, CytomX Therapeutics, Daiichi Sankyo, Gilead, Ellipses Pharma, 4D Pharma, OncoSec Medical Inc, BeyondSpring Pharmaceuticals, OncXerna, Zymeworks, Zentalis, Blueprint Medicines, Reveal Genomics, ARC Therapeutics, Myovant, Zetagen, Umoja Biopharma, Menarini/Stemline, Aadi Biopharma, Bayer, Jazz Pharmaceuticals, Exelixis, Novartis, Nanonstring, and Cyclacel.

A version of this article appeared on Medscape.com .