Geriatrics

LONG BEACH, CALIF. – For years, clinicians have debated whether prescribing statins to patients older than 75 for the prevention of cardiovascular events is appropriate.

In 2022, the U.S. Preventive Services Task Force concluded that scientific evidence was insufficient to assess the balance between the benefits and harms of the therapy for this older population.

At a session of the annual meeting of the American Geriatrics Society, experts laid out new preliminary recommendations of the AGS and the National Lipid Association on assessing risk and deciding on treatment.

The group concluded that LDL cholesterol levels are associated with incident arteriosclerotic cardiovascular disease (ASCVD), that the coronary artery calcium (CAC) score can be a valuable measure, and that statins may be reasonable to prescribe, even given the risks that have been linked to statins, such as that for muscle pain. Final recommendations are expected by fall 2023.

“This is still a work in progress,” said Daniel E. Forman, MD, professor of medicine and chair of geriatric cardiology at the University of Pittsburgh.

The AGS-NLA panel concluded that, for those aged 75 or older without established ASCVD, LDL cholesterol is associated with incident ASCVD, the only recommendation to be given a class I (strong) rating; others were classed as moderate or weak.

Dr. Forman reviewed the evidence for lowering LDL cholesterol to decrease ASCVD, citing a 2018 study that concluded, “Reverse causation may contribute to the association of lower TC with higher mortality in nonrandomized studies.”

However, research overall shows that, as LDL cholesterol levels increase, patients are more likely to experience a heart event.

Dr. Forman noted that the utility of equations for assessing 5- or 10-year risk of ASCVD is uncertain. However, he said, traditional risk factors, such as family history and ethnicity, still have value.

Assessing risk “has been enriched in the past few years by the introduction of the coronary artery calcium [CAC] score,” he said.

Lower scores predict lower rates of CVD events, Forman said. The AGS-NLA recommends measuring CAC if clinical uncertainty exists about the value of statins.

“It’s reasonable to measure CAC and to withhold statins when the CAC is zero,” Dr. Forman said. “When the CAC score is zero ... the risk of having a cardiovascular event is really next to nil. Patients are happy to know they have a CAC of zero.”

Likewise, patients appreciate knowing whether their score is high, which would indicate increased risk. He said the CAC score is underused by geriatric physicians.

The group also determined, after reviewing the research, that starting treatment is reasonable for patients with an LDL cholesterol level of 70-189 if they have no life-limiting illness and their life expectancy is over 5 years.

Other preliminary recommendations include the use of statins for those aged 75 and older, irrespective of risk for statin-associated muscle symptoms, type 2 diabetes, or impaired cognition. These associations are often weak, Dr. Forman added.
 

Focusing on person-centered decisions

Ariel Green, MD, MPH, PhD, associate professor of medicine at Johns Hopkins University, Baltimore, said statin therapy “should be individualized” to weigh benefits, noncardiac risks, and other considerations.

Clinicians can incorporate life expectancy into prevention decisions using tools such as ePrognosis, from the University of California, San Francisco, Dr. Green said.

If life expectancy is greater than the time to benefit, statin therapy may help. Dr. Green cited research that showed that 2.5 years of statin therapy was needed to prevent one major adverse cardiovascular event (MACE) per 100 patients in a population aged 50-75. Other data show reductions in MACE for those older than 75, but overall, the data are limited in this population.

The proposed recommendation is to use tools such as life tables that include comorbid conditions and functional status to guide clinical decisions.

“Another aspect of assessing net benefits of statin therapy is to consider competing health risks,” Dr. Green said.

The group recommends considering using competing risk-adjusted CVD models, though these are not widely used.

The group also recommends integrating screenings for frailty (Clinical Frailty Scale), dementia (Mini-Cog), and functional status (Vulnerable Elders Scale–13) into assessments.

“The presence of these syndromes should prompt elicitation of patient values and preferences related to prevention and medication use,” Dr. Green said.

Clinicians can use decision aids, but these are not always practical, owing to obstacles such as patients’ cognitive problems, Dr. Green said.

“Another approach is asking people to prioritize a set of universal health outcomes that apply across health conditions, such as maintaining independence, staying alive, reducing, or eliminating symptoms and focusing on comfort,” Dr. Green said.

She addressed the evidence about deprescribing statins, with a focus on those with a life expectancy of less than a year. Researchers have found an increase in quality of life and no increases in cardiovascular events or death when statins were deprescribed.
 

A welcome framework

Cory Krueger, MD, an internal medicine and geriatric physician in Cornville, Ariz., who attended the talk, said he welcomed the presentation, in which preliminary recommendations were explained.

“This has been a controversial area in geriatrics,” Dr. Krueger said. “At least this gave me a framework for discussing this with my patients in a reasonable way.”

Dr. Forman and Dr. Krueger disclosed no relevant financial relationships. Dr. Green receives funding from the National Institute of Aging and Impact Collaboratory.

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

LONG BEACH, CALIF. – For years, clinicians have debated whether prescribing statins to patients older than 75 for the prevention of cardiovascular events is appropriate.

In 2022, the U.S. Preventive Services Task Force concluded that scientific evidence was insufficient to assess the balance between the benefits and harms of the therapy for this older population.

At a session of the annual meeting of the American Geriatrics Society, experts laid out new preliminary recommendations of the AGS and the National Lipid Association on assessing risk and deciding on treatment.

The group concluded that LDL cholesterol levels are associated with incident arteriosclerotic cardiovascular disease (ASCVD), that the coronary artery calcium (CAC) score can be a valuable measure, and that statins may be reasonable to prescribe, even given the risks that have been linked to statins, such as that for muscle pain. Final recommendations are expected by fall 2023.

“This is still a work in progress,” said Daniel E. Forman, MD, professor of medicine and chair of geriatric cardiology at the University of Pittsburgh.

The AGS-NLA panel concluded that, for those aged 75 or older without established ASCVD, LDL cholesterol is associated with incident ASCVD, the only recommendation to be given a class I (strong) rating; others were classed as moderate or weak.

Dr. Forman reviewed the evidence for lowering LDL cholesterol to decrease ASCVD, citing a 2018 study that concluded, “Reverse causation may contribute to the association of lower TC with higher mortality in nonrandomized studies.”

However, research overall shows that, as LDL cholesterol levels increase, patients are more likely to experience a heart event.

Dr. Forman noted that the utility of equations for assessing 5- or 10-year risk of ASCVD is uncertain. However, he said, traditional risk factors, such as family history and ethnicity, still have value.

Assessing risk “has been enriched in the past few years by the introduction of the coronary artery calcium [CAC] score,” he said.

Lower scores predict lower rates of CVD events, Forman said. The AGS-NLA recommends measuring CAC if clinical uncertainty exists about the value of statins.

“It’s reasonable to measure CAC and to withhold statins when the CAC is zero,” Dr. Forman said. “When the CAC score is zero ... the risk of having a cardiovascular event is really next to nil. Patients are happy to know they have a CAC of zero.”

Likewise, patients appreciate knowing whether their score is high, which would indicate increased risk. He said the CAC score is underused by geriatric physicians.

The group also determined, after reviewing the research, that starting treatment is reasonable for patients with an LDL cholesterol level of 70-189 if they have no life-limiting illness and their life expectancy is over 5 years.

Other preliminary recommendations include the use of statins for those aged 75 and older, irrespective of risk for statin-associated muscle symptoms, type 2 diabetes, or impaired cognition. These associations are often weak, Dr. Forman added.
 

Focusing on person-centered decisions

Ariel Green, MD, MPH, PhD, associate professor of medicine at Johns Hopkins University, Baltimore, said statin therapy “should be individualized” to weigh benefits, noncardiac risks, and other considerations.

Clinicians can incorporate life expectancy into prevention decisions using tools such as ePrognosis, from the University of California, San Francisco, Dr. Green said.

If life expectancy is greater than the time to benefit, statin therapy may help. Dr. Green cited research that showed that 2.5 years of statin therapy was needed to prevent one major adverse cardiovascular event (MACE) per 100 patients in a population aged 50-75. Other data show reductions in MACE for those older than 75, but overall, the data are limited in this population.

The proposed recommendation is to use tools such as life tables that include comorbid conditions and functional status to guide clinical decisions.

“Another aspect of assessing net benefits of statin therapy is to consider competing health risks,” Dr. Green said.

The group recommends considering using competing risk-adjusted CVD models, though these are not widely used.

The group also recommends integrating screenings for frailty (Clinical Frailty Scale), dementia (Mini-Cog), and functional status (Vulnerable Elders Scale–13) into assessments.

“The presence of these syndromes should prompt elicitation of patient values and preferences related to prevention and medication use,” Dr. Green said.

Clinicians can use decision aids, but these are not always practical, owing to obstacles such as patients’ cognitive problems, Dr. Green said.

“Another approach is asking people to prioritize a set of universal health outcomes that apply across health conditions, such as maintaining independence, staying alive, reducing, or eliminating symptoms and focusing on comfort,” Dr. Green said.

She addressed the evidence about deprescribing statins, with a focus on those with a life expectancy of less than a year. Researchers have found an increase in quality of life and no increases in cardiovascular events or death when statins were deprescribed.
 

A welcome framework

Cory Krueger, MD, an internal medicine and geriatric physician in Cornville, Ariz., who attended the talk, said he welcomed the presentation, in which preliminary recommendations were explained.

“This has been a controversial area in geriatrics,” Dr. Krueger said. “At least this gave me a framework for discussing this with my patients in a reasonable way.”

Dr. Forman and Dr. Krueger disclosed no relevant financial relationships. Dr. Green receives funding from the National Institute of Aging and Impact Collaboratory.

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

LONG BEACH, CALIF. – For years, clinicians have debated whether prescribing statins to patients older than 75 for the prevention of cardiovascular events is appropriate.

In 2022, the U.S. Preventive Services Task Force concluded that scientific evidence was insufficient to assess the balance between the benefits and harms of the therapy for this older population.

At a session of the annual meeting of the American Geriatrics Society, experts laid out new preliminary recommendations of the AGS and the National Lipid Association on assessing risk and deciding on treatment.

The group concluded that LDL cholesterol levels are associated with incident arteriosclerotic cardiovascular disease (ASCVD), that the coronary artery calcium (CAC) score can be a valuable measure, and that statins may be reasonable to prescribe, even given the risks that have been linked to statins, such as that for muscle pain. Final recommendations are expected by fall 2023.

“This is still a work in progress,” said Daniel E. Forman, MD, professor of medicine and chair of geriatric cardiology at the University of Pittsburgh.

The AGS-NLA panel concluded that, for those aged 75 or older without established ASCVD, LDL cholesterol is associated with incident ASCVD, the only recommendation to be given a class I (strong) rating; others were classed as moderate or weak.

Dr. Forman reviewed the evidence for lowering LDL cholesterol to decrease ASCVD, citing a 2018 study that concluded, “Reverse causation may contribute to the association of lower TC with higher mortality in nonrandomized studies.”

However, research overall shows that, as LDL cholesterol levels increase, patients are more likely to experience a heart event.

Dr. Forman noted that the utility of equations for assessing 5- or 10-year risk of ASCVD is uncertain. However, he said, traditional risk factors, such as family history and ethnicity, still have value.

Assessing risk “has been enriched in the past few years by the introduction of the coronary artery calcium [CAC] score,” he said.

Lower scores predict lower rates of CVD events, Forman said. The AGS-NLA recommends measuring CAC if clinical uncertainty exists about the value of statins.

“It’s reasonable to measure CAC and to withhold statins when the CAC is zero,” Dr. Forman said. “When the CAC score is zero ... the risk of having a cardiovascular event is really next to nil. Patients are happy to know they have a CAC of zero.”

Likewise, patients appreciate knowing whether their score is high, which would indicate increased risk. He said the CAC score is underused by geriatric physicians.

The group also determined, after reviewing the research, that starting treatment is reasonable for patients with an LDL cholesterol level of 70-189 if they have no life-limiting illness and their life expectancy is over 5 years.

Other preliminary recommendations include the use of statins for those aged 75 and older, irrespective of risk for statin-associated muscle symptoms, type 2 diabetes, or impaired cognition. These associations are often weak, Dr. Forman added.
 

Focusing on person-centered decisions

Ariel Green, MD, MPH, PhD, associate professor of medicine at Johns Hopkins University, Baltimore, said statin therapy “should be individualized” to weigh benefits, noncardiac risks, and other considerations.

Clinicians can incorporate life expectancy into prevention decisions using tools such as ePrognosis, from the University of California, San Francisco, Dr. Green said.

If life expectancy is greater than the time to benefit, statin therapy may help. Dr. Green cited research that showed that 2.5 years of statin therapy was needed to prevent one major adverse cardiovascular event (MACE) per 100 patients in a population aged 50-75. Other data show reductions in MACE for those older than 75, but overall, the data are limited in this population.

The proposed recommendation is to use tools such as life tables that include comorbid conditions and functional status to guide clinical decisions.

“Another aspect of assessing net benefits of statin therapy is to consider competing health risks,” Dr. Green said.

The group recommends considering using competing risk-adjusted CVD models, though these are not widely used.

The group also recommends integrating screenings for frailty (Clinical Frailty Scale), dementia (Mini-Cog), and functional status (Vulnerable Elders Scale–13) into assessments.

“The presence of these syndromes should prompt elicitation of patient values and preferences related to prevention and medication use,” Dr. Green said.

Clinicians can use decision aids, but these are not always practical, owing to obstacles such as patients’ cognitive problems, Dr. Green said.

“Another approach is asking people to prioritize a set of universal health outcomes that apply across health conditions, such as maintaining independence, staying alive, reducing, or eliminating symptoms and focusing on comfort,” Dr. Green said.

She addressed the evidence about deprescribing statins, with a focus on those with a life expectancy of less than a year. Researchers have found an increase in quality of life and no increases in cardiovascular events or death when statins were deprescribed.
 

A welcome framework

Cory Krueger, MD, an internal medicine and geriatric physician in Cornville, Ariz., who attended the talk, said he welcomed the presentation, in which preliminary recommendations were explained.

“This has been a controversial area in geriatrics,” Dr. Krueger said. “At least this gave me a framework for discussing this with my patients in a reasonable way.”

Dr. Forman and Dr. Krueger disclosed no relevant financial relationships. Dr. Green receives funding from the National Institute of Aging and Impact Collaboratory.

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

A new Canadian guideline on screening for the primary prevention of fragility fractures recommends risk assessment first, before bone mineral density (BMD) testing, for women aged 65 and older. For younger women and men aged 40 and older, screening is not recommended.

To develop the guideline, a writing group from Canadian Task Force on Preventive Health Care commissioned systematic reviews of studies on the benefits and harms of fragility fracture screenings; the predictive accuracy of current risk-assessment tools; patient acceptability; and benefits of treatment. Treatment harms were analyzed via a rapid overview of reviews.

The guideline, published online in the Canadian Medical Association Journal, is aimed at primary care practitioners for their community-dwelling patients aged 40 and older. The recommendations do not apply to people already taking preventive drugs.

Nondrug treatments were beyond the scope of the current guideline, but guidelines on the prevention of falls and other strategies are planned, Roland Grad, MD, a guideline author and associate professor at McGill University in Montreal, told this news organization.

The new guideline says that women aged 65 and older may be able to avoid fracture through screening and preventive medication. An individual’s fracture risk can be estimated with a new Fragility Fractures Decision Aid, which uses the Canadian FRAX risk-assessment tool.

“A risk assessment–first approach promotes shared decision-making with the patient, based on best medical evidence,” Dr. Grad said.

“To help clinicians, we have created an infographic with visuals to communicate the time spent on BMD vs risk assessment first.”
 

New evidence

“At least three things motivated this new guideline,” Dr. Grad said. “When we started work on this prior to the pandemic, we saw a need for updated guidance on screening to prevent fragility fractures. We were also aware of new evidence from the publication of screening trials in females older than 65.”

To conduct the risk assessment in older women, clinicians are advised to do the following:

• Use the decision aid (which patients can also use on their own).
• Use the 10-year absolute risk of major osteoporotic fracture to facilitate shared decision-making about possible benefits and harms of preventive pharmacotherapy.
• If pharmacotherapy is being considered, request a BMD using DXA of the femoral neck, then reestimate the fracture risk by adding the BMD T-score into the FRAX.

Potential harms associated with various treatments, with varying levels of evidence, include the following: with alendronate and denosumab, nonserious gastrointestinal adverse events; with denosumab, rash, eczema, and infections; with zoledronic acid, nonserious events, such as headache and flulike symptoms; and with alendronate and bisphosphonates, rare but serious harms of atypical femoral fracture and osteonecrosis of the jaw.

“These recommendations emphasize the importance of good clinical practice, where clinicians are alert to changes in physical health and patient well-being,” the authors wrote. “Clinicians should also be aware of the importance of secondary prevention (i.e., after fracture) and manage patients accordingly.”

“This is an important topic,” Dr. Grad said. “Fragility fractures are consequential for individuals and for our publicly funded health care system. We anticipate questions from clinicians about the time needed to screen with the risk assessment–first strategy. Our modeling work suggests time savings with [this] strategy compared to a strategy of BMD testing first. Following our recommendations may lead to a reduction in BMD testing.”

To promote the guideline, the CMAJ has recorded a podcast and will use other strategies to increase awareness, Dr. Grad said. “The Canadian Task Force has a communications strategy that includes outreach to primary care, stakeholder webinars, social media, partnerships, and other tactics. The College of Family Physicians of Canada has endorsed the guideline and will help promote to its members.”
 

Other at-risk groups?

Aliya Khan, MD, FRCPC, FACP, FACE, professor in the divisions of endocrinology and metabolism and geriatrics and director of the fellowship in metabolic bone diseases at McMaster University in Hamilton, Ont., told this news organization she agrees with the strategy of evaluating women aged 65 and older for fracture risk.

“The decision aid is useful, but I would like to see it expanded to other circumstances and situations,” she said.

For example, Dr. Khan would like to see recommendations for younger women and for men of all ages regarding secondary causes of osteoporosis or medications known to have a detrimental effect on bone health. By not addressing these patients, she said, “we may miss patients who would benefit from a fracture risk assessment and potentially treatment to prevent low-trauma fractures.”

A recommendation for younger postmenopausal women was included in the most recent Society of Obstetricians and Gynaecologists Canada guideline, she noted.

Overall, she said, “I believe these recommendations will reduce the excess or inappropriate use of BMD testing and that is welcome.”

Funding for the Canadian Task Force on Preventive Health Care is provided by the Public Health Agency of Canada. The task force members report no relevant financial relationships.

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

A new Canadian guideline on screening for the primary prevention of fragility fractures recommends risk assessment first, before bone mineral density (BMD) testing, for women aged 65 and older. For younger women and men aged 40 and older, screening is not recommended.

To develop the guideline, a writing group from Canadian Task Force on Preventive Health Care commissioned systematic reviews of studies on the benefits and harms of fragility fracture screenings; the predictive accuracy of current risk-assessment tools; patient acceptability; and benefits of treatment. Treatment harms were analyzed via a rapid overview of reviews.

The guideline, published online in the Canadian Medical Association Journal, is aimed at primary care practitioners for their community-dwelling patients aged 40 and older. The recommendations do not apply to people already taking preventive drugs.

Nondrug treatments were beyond the scope of the current guideline, but guidelines on the prevention of falls and other strategies are planned, Roland Grad, MD, a guideline author and associate professor at McGill University in Montreal, told this news organization.

The new guideline says that women aged 65 and older may be able to avoid fracture through screening and preventive medication. An individual’s fracture risk can be estimated with a new Fragility Fractures Decision Aid, which uses the Canadian FRAX risk-assessment tool.

“A risk assessment–first approach promotes shared decision-making with the patient, based on best medical evidence,” Dr. Grad said.

“To help clinicians, we have created an infographic with visuals to communicate the time spent on BMD vs risk assessment first.”
 

New evidence

“At least three things motivated this new guideline,” Dr. Grad said. “When we started work on this prior to the pandemic, we saw a need for updated guidance on screening to prevent fragility fractures. We were also aware of new evidence from the publication of screening trials in females older than 65.”

To conduct the risk assessment in older women, clinicians are advised to do the following:

• Use the decision aid (which patients can also use on their own).
• Use the 10-year absolute risk of major osteoporotic fracture to facilitate shared decision-making about possible benefits and harms of preventive pharmacotherapy.
• If pharmacotherapy is being considered, request a BMD using DXA of the femoral neck, then reestimate the fracture risk by adding the BMD T-score into the FRAX.

Potential harms associated with various treatments, with varying levels of evidence, include the following: with alendronate and denosumab, nonserious gastrointestinal adverse events; with denosumab, rash, eczema, and infections; with zoledronic acid, nonserious events, such as headache and flulike symptoms; and with alendronate and bisphosphonates, rare but serious harms of atypical femoral fracture and osteonecrosis of the jaw.

“These recommendations emphasize the importance of good clinical practice, where clinicians are alert to changes in physical health and patient well-being,” the authors wrote. “Clinicians should also be aware of the importance of secondary prevention (i.e., after fracture) and manage patients accordingly.”

“This is an important topic,” Dr. Grad said. “Fragility fractures are consequential for individuals and for our publicly funded health care system. We anticipate questions from clinicians about the time needed to screen with the risk assessment–first strategy. Our modeling work suggests time savings with [this] strategy compared to a strategy of BMD testing first. Following our recommendations may lead to a reduction in BMD testing.”

To promote the guideline, the CMAJ has recorded a podcast and will use other strategies to increase awareness, Dr. Grad said. “The Canadian Task Force has a communications strategy that includes outreach to primary care, stakeholder webinars, social media, partnerships, and other tactics. The College of Family Physicians of Canada has endorsed the guideline and will help promote to its members.”
 

Other at-risk groups?

Aliya Khan, MD, FRCPC, FACP, FACE, professor in the divisions of endocrinology and metabolism and geriatrics and director of the fellowship in metabolic bone diseases at McMaster University in Hamilton, Ont., told this news organization she agrees with the strategy of evaluating women aged 65 and older for fracture risk.

“The decision aid is useful, but I would like to see it expanded to other circumstances and situations,” she said.

For example, Dr. Khan would like to see recommendations for younger women and for men of all ages regarding secondary causes of osteoporosis or medications known to have a detrimental effect on bone health. By not addressing these patients, she said, “we may miss patients who would benefit from a fracture risk assessment and potentially treatment to prevent low-trauma fractures.”

A recommendation for younger postmenopausal women was included in the most recent Society of Obstetricians and Gynaecologists Canada guideline, she noted.

Overall, she said, “I believe these recommendations will reduce the excess or inappropriate use of BMD testing and that is welcome.”

Funding for the Canadian Task Force on Preventive Health Care is provided by the Public Health Agency of Canada. The task force members report no relevant financial relationships.

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

A new Canadian guideline on screening for the primary prevention of fragility fractures recommends risk assessment first, before bone mineral density (BMD) testing, for women aged 65 and older. For younger women and men aged 40 and older, screening is not recommended.

To develop the guideline, a writing group from Canadian Task Force on Preventive Health Care commissioned systematic reviews of studies on the benefits and harms of fragility fracture screenings; the predictive accuracy of current risk-assessment tools; patient acceptability; and benefits of treatment. Treatment harms were analyzed via a rapid overview of reviews.

The guideline, published online in the Canadian Medical Association Journal, is aimed at primary care practitioners for their community-dwelling patients aged 40 and older. The recommendations do not apply to people already taking preventive drugs.

Nondrug treatments were beyond the scope of the current guideline, but guidelines on the prevention of falls and other strategies are planned, Roland Grad, MD, a guideline author and associate professor at McGill University in Montreal, told this news organization.

The new guideline says that women aged 65 and older may be able to avoid fracture through screening and preventive medication. An individual’s fracture risk can be estimated with a new Fragility Fractures Decision Aid, which uses the Canadian FRAX risk-assessment tool.

“A risk assessment–first approach promotes shared decision-making with the patient, based on best medical evidence,” Dr. Grad said.

“To help clinicians, we have created an infographic with visuals to communicate the time spent on BMD vs risk assessment first.”
 

New evidence

“At least three things motivated this new guideline,” Dr. Grad said. “When we started work on this prior to the pandemic, we saw a need for updated guidance on screening to prevent fragility fractures. We were also aware of new evidence from the publication of screening trials in females older than 65.”

To conduct the risk assessment in older women, clinicians are advised to do the following:

• Use the decision aid (which patients can also use on their own).
• Use the 10-year absolute risk of major osteoporotic fracture to facilitate shared decision-making about possible benefits and harms of preventive pharmacotherapy.
• If pharmacotherapy is being considered, request a BMD using DXA of the femoral neck, then reestimate the fracture risk by adding the BMD T-score into the FRAX.

Potential harms associated with various treatments, with varying levels of evidence, include the following: with alendronate and denosumab, nonserious gastrointestinal adverse events; with denosumab, rash, eczema, and infections; with zoledronic acid, nonserious events, such as headache and flulike symptoms; and with alendronate and bisphosphonates, rare but serious harms of atypical femoral fracture and osteonecrosis of the jaw.

“These recommendations emphasize the importance of good clinical practice, where clinicians are alert to changes in physical health and patient well-being,” the authors wrote. “Clinicians should also be aware of the importance of secondary prevention (i.e., after fracture) and manage patients accordingly.”

“This is an important topic,” Dr. Grad said. “Fragility fractures are consequential for individuals and for our publicly funded health care system. We anticipate questions from clinicians about the time needed to screen with the risk assessment–first strategy. Our modeling work suggests time savings with [this] strategy compared to a strategy of BMD testing first. Following our recommendations may lead to a reduction in BMD testing.”

To promote the guideline, the CMAJ has recorded a podcast and will use other strategies to increase awareness, Dr. Grad said. “The Canadian Task Force has a communications strategy that includes outreach to primary care, stakeholder webinars, social media, partnerships, and other tactics. The College of Family Physicians of Canada has endorsed the guideline and will help promote to its members.”
 

Other at-risk groups?

Aliya Khan, MD, FRCPC, FACP, FACE, professor in the divisions of endocrinology and metabolism and geriatrics and director of the fellowship in metabolic bone diseases at McMaster University in Hamilton, Ont., told this news organization she agrees with the strategy of evaluating women aged 65 and older for fracture risk.

“The decision aid is useful, but I would like to see it expanded to other circumstances and situations,” she said.

For example, Dr. Khan would like to see recommendations for younger women and for men of all ages regarding secondary causes of osteoporosis or medications known to have a detrimental effect on bone health. By not addressing these patients, she said, “we may miss patients who would benefit from a fracture risk assessment and potentially treatment to prevent low-trauma fractures.”

A recommendation for younger postmenopausal women was included in the most recent Society of Obstetricians and Gynaecologists Canada guideline, she noted.

Overall, she said, “I believe these recommendations will reduce the excess or inappropriate use of BMD testing and that is welcome.”

Funding for the Canadian Task Force on Preventive Health Care is provided by the Public Health Agency of Canada. The task force members report no relevant financial relationships.

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

An 85-year-old woman is brought to the emergency department after a syncopal episode. Her caregivers report a similar episode 2 weeks ago, but she recovered so quickly they did not seek evaluation for her.

Medications: Omeprazole 20 mg, pravastatin 40 mg, citalopram 10 mg, albuterol, donepezil 10 mg, isosorbide mononitrate 60 mg, and calcium. On exam, blood pressure is 100/60 mm Hg, pulse 55. ECG indicates bradycardia with normal intervals. What drug most likely caused her syncope?

A. Citalopram

B. Pravastatin

C. Donepezil

D. Isosorbide

E. Calcium

This woman’s syncope is likely caused by donepezil. Citalopram can lengthen the QT interval, especially in elderly patients, but the normal intervals on ECG eliminate this possibility. Donepezil can cause bradycardia, which can contribute to syncope.

Hernandez and colleagues evaluated a cohort of veterans with dementia over an 8-year period.¹ They found that there was a 1.4-fold increased risk of bradycardia in patients with dementia treated with an acetylcholine inhibitor (compared with that in patients who were not taking these medications) and that there was a dose-dependent increase in risk for patients on donepezil.

Park-Wyllie et al. found in a study of 1.4 million older adults a greater than twofold risk of hospitalization for bradycardia in patients treated with a cholinesterase inhibitor.² Gill and colleagues performed a population-based cohort study of 19,803 elderly patients with dementia who were prescribed cholinesterase inhibitors, and compared them to age-matched controls.³ They found increased hospital visits for syncope in people receiving cholinesterase inhibitors (hazard ratio, 1.76; 95% confidence interval, 1.57-1.98). Other syncope-related events were also more common in people receiving cholinesterase inhibitors, compared with controls: hospital visits for bradycardia (HR, 1.69; 95% CI, 1.32-2.15), permanent pacemaker insertion (HR, 1.49; 95% CI, 1.12-2.00), and hip fracture (HR, 1.18; (95% CI, 1.04-1.34).

Nausea, vomiting, and weight loss are much more common than the rarer side effects of bradycardia and syncope. The frequency of gastroenterological side effects is up to 25%. Cholinesterase inhibitors have modest effects on cognitive function with a high number needed to treat (NNT) of 10, and an NNT as high as 100 for global function. The number needed to harm (NNH) is 4, when gastrointestinal symptoms are added in.⁴ Another important, problematic side effect of cholinesterase inhibitors is urinary incontinence. This often leads to patients receiving medications, to combat this side effect, that may worsen cognitive function.

Another commonly used medication that scares me in certain circumstances is trimethoprim-sulfamethoxazole. My main concern is when it is used in patients who are elderly, have chronic kidney disease, or are taking other medications that can cause hyperkalemia (ACEIs, ARBs, potassium-sparing diuretics including spironolactone). Hyperkalemia is a real concern in these patient populations. Trimethoprim reduces renal potassium excretion through the competitive inhibition of sodium channels in the distal nephron, in a manner similar to the potassium-sparing diuretic amiloride. Hospitalizations for hyperkalemia are more common in patients who take ACEIs and ARBs and are prescribed trimethoprim-sulfamethoxazole, compared with other antibiotics.⁵

Sudden cardiac death is also more common in patients who are taking ACEIs or ARBs and receive trimethoprim-sulfamethoxazole.⁶ Trimethoprim-sulfamethoxazole also has a powerful interaction with warfarin, both displacing warfarin from albumin and inhibiting its metabolism. It raises the INR (international normalized ratio) in warfarin-treated patients much greater than do other antibiotics.⁷
 

Pearls

• Think carefully about the use of cholinesterase inhibitors because of the unfavorable NNH vs. NNT.
• Use caution prescribing trimethoprim for patients who are elderly, especially if they are on an ACEI, an ARB, or spironolactone, and in patients with chronic kidney disease.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at dpaauw@uw.edu.

References

1. Hernandez RK et al. J Am Geriatr Soc. 2009;57:1997-2003.

2. Park-Wyllie LY et al. PLoS Med. 2009;6:e1000157.

3. Gill SS et al. Arch Intern Med 2009;169:867-73.

4. Peters KR. J Am Geriatr Soc. 2013 Jul;61(7):1170-4.

5. Antoniou TN et al. Arch Intern Med. 2010;170(12):1045-9.

6. Fralick M et al. BMJ. 2014 Oct 30;349:g6196.

7. Glasheen JJ et al. J Gen Intern Med. 2005 Jul;20(7):653-6.

An 85-year-old woman is brought to the emergency department after a syncopal episode. Her caregivers report a similar episode 2 weeks ago, but she recovered so quickly they did not seek evaluation for her.

Medications: Omeprazole 20 mg, pravastatin 40 mg, citalopram 10 mg, albuterol, donepezil 10 mg, isosorbide mononitrate 60 mg, and calcium. On exam, blood pressure is 100/60 mm Hg, pulse 55. ECG indicates bradycardia with normal intervals. What drug most likely caused her syncope?

A. Citalopram

B. Pravastatin

C. Donepezil

D. Isosorbide

E. Calcium

This woman’s syncope is likely caused by donepezil. Citalopram can lengthen the QT interval, especially in elderly patients, but the normal intervals on ECG eliminate this possibility. Donepezil can cause bradycardia, which can contribute to syncope.

Hernandez and colleagues evaluated a cohort of veterans with dementia over an 8-year period.¹ They found that there was a 1.4-fold increased risk of bradycardia in patients with dementia treated with an acetylcholine inhibitor (compared with that in patients who were not taking these medications) and that there was a dose-dependent increase in risk for patients on donepezil.

Park-Wyllie et al. found in a study of 1.4 million older adults a greater than twofold risk of hospitalization for bradycardia in patients treated with a cholinesterase inhibitor.² Gill and colleagues performed a population-based cohort study of 19,803 elderly patients with dementia who were prescribed cholinesterase inhibitors, and compared them to age-matched controls.³ They found increased hospital visits for syncope in people receiving cholinesterase inhibitors (hazard ratio, 1.76; 95% confidence interval, 1.57-1.98). Other syncope-related events were also more common in people receiving cholinesterase inhibitors, compared with controls: hospital visits for bradycardia (HR, 1.69; 95% CI, 1.32-2.15), permanent pacemaker insertion (HR, 1.49; 95% CI, 1.12-2.00), and hip fracture (HR, 1.18; (95% CI, 1.04-1.34).

Nausea, vomiting, and weight loss are much more common than the rarer side effects of bradycardia and syncope. The frequency of gastroenterological side effects is up to 25%. Cholinesterase inhibitors have modest effects on cognitive function with a high number needed to treat (NNT) of 10, and an NNT as high as 100 for global function. The number needed to harm (NNH) is 4, when gastrointestinal symptoms are added in.⁴ Another important, problematic side effect of cholinesterase inhibitors is urinary incontinence. This often leads to patients receiving medications, to combat this side effect, that may worsen cognitive function.

Another commonly used medication that scares me in certain circumstances is trimethoprim-sulfamethoxazole. My main concern is when it is used in patients who are elderly, have chronic kidney disease, or are taking other medications that can cause hyperkalemia (ACEIs, ARBs, potassium-sparing diuretics including spironolactone). Hyperkalemia is a real concern in these patient populations. Trimethoprim reduces renal potassium excretion through the competitive inhibition of sodium channels in the distal nephron, in a manner similar to the potassium-sparing diuretic amiloride. Hospitalizations for hyperkalemia are more common in patients who take ACEIs and ARBs and are prescribed trimethoprim-sulfamethoxazole, compared with other antibiotics.⁵

Sudden cardiac death is also more common in patients who are taking ACEIs or ARBs and receive trimethoprim-sulfamethoxazole.⁶ Trimethoprim-sulfamethoxazole also has a powerful interaction with warfarin, both displacing warfarin from albumin and inhibiting its metabolism. It raises the INR (international normalized ratio) in warfarin-treated patients much greater than do other antibiotics.⁷
 

Pearls

• Think carefully about the use of cholinesterase inhibitors because of the unfavorable NNH vs. NNT.
• Use caution prescribing trimethoprim for patients who are elderly, especially if they are on an ACEI, an ARB, or spironolactone, and in patients with chronic kidney disease.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at dpaauw@uw.edu.

References

1. Hernandez RK et al. J Am Geriatr Soc. 2009;57:1997-2003.

2. Park-Wyllie LY et al. PLoS Med. 2009;6:e1000157.

3. Gill SS et al. Arch Intern Med 2009;169:867-73.

4. Peters KR. J Am Geriatr Soc. 2013 Jul;61(7):1170-4.

5. Antoniou TN et al. Arch Intern Med. 2010;170(12):1045-9.

6. Fralick M et al. BMJ. 2014 Oct 30;349:g6196.

7. Glasheen JJ et al. J Gen Intern Med. 2005 Jul;20(7):653-6.

An 85-year-old woman is brought to the emergency department after a syncopal episode. Her caregivers report a similar episode 2 weeks ago, but she recovered so quickly they did not seek evaluation for her.

Medications: Omeprazole 20 mg, pravastatin 40 mg, citalopram 10 mg, albuterol, donepezil 10 mg, isosorbide mononitrate 60 mg, and calcium. On exam, blood pressure is 100/60 mm Hg, pulse 55. ECG indicates bradycardia with normal intervals. What drug most likely caused her syncope?

A. Citalopram

B. Pravastatin

C. Donepezil

D. Isosorbide

E. Calcium

This woman’s syncope is likely caused by donepezil. Citalopram can lengthen the QT interval, especially in elderly patients, but the normal intervals on ECG eliminate this possibility. Donepezil can cause bradycardia, which can contribute to syncope.

Hernandez and colleagues evaluated a cohort of veterans with dementia over an 8-year period.¹ They found that there was a 1.4-fold increased risk of bradycardia in patients with dementia treated with an acetylcholine inhibitor (compared with that in patients who were not taking these medications) and that there was a dose-dependent increase in risk for patients on donepezil.

Park-Wyllie et al. found in a study of 1.4 million older adults a greater than twofold risk of hospitalization for bradycardia in patients treated with a cholinesterase inhibitor.² Gill and colleagues performed a population-based cohort study of 19,803 elderly patients with dementia who were prescribed cholinesterase inhibitors, and compared them to age-matched controls.³ They found increased hospital visits for syncope in people receiving cholinesterase inhibitors (hazard ratio, 1.76; 95% confidence interval, 1.57-1.98). Other syncope-related events were also more common in people receiving cholinesterase inhibitors, compared with controls: hospital visits for bradycardia (HR, 1.69; 95% CI, 1.32-2.15), permanent pacemaker insertion (HR, 1.49; 95% CI, 1.12-2.00), and hip fracture (HR, 1.18; (95% CI, 1.04-1.34).

Nausea, vomiting, and weight loss are much more common than the rarer side effects of bradycardia and syncope. The frequency of gastroenterological side effects is up to 25%. Cholinesterase inhibitors have modest effects on cognitive function with a high number needed to treat (NNT) of 10, and an NNT as high as 100 for global function. The number needed to harm (NNH) is 4, when gastrointestinal symptoms are added in.⁴ Another important, problematic side effect of cholinesterase inhibitors is urinary incontinence. This often leads to patients receiving medications, to combat this side effect, that may worsen cognitive function.

Another commonly used medication that scares me in certain circumstances is trimethoprim-sulfamethoxazole. My main concern is when it is used in patients who are elderly, have chronic kidney disease, or are taking other medications that can cause hyperkalemia (ACEIs, ARBs, potassium-sparing diuretics including spironolactone). Hyperkalemia is a real concern in these patient populations. Trimethoprim reduces renal potassium excretion through the competitive inhibition of sodium channels in the distal nephron, in a manner similar to the potassium-sparing diuretic amiloride. Hospitalizations for hyperkalemia are more common in patients who take ACEIs and ARBs and are prescribed trimethoprim-sulfamethoxazole, compared with other antibiotics.⁵

Sudden cardiac death is also more common in patients who are taking ACEIs or ARBs and receive trimethoprim-sulfamethoxazole.⁶ Trimethoprim-sulfamethoxazole also has a powerful interaction with warfarin, both displacing warfarin from albumin and inhibiting its metabolism. It raises the INR (international normalized ratio) in warfarin-treated patients much greater than do other antibiotics.⁷
 

Pearls

• Think carefully about the use of cholinesterase inhibitors because of the unfavorable NNH vs. NNT.
• Use caution prescribing trimethoprim for patients who are elderly, especially if they are on an ACEI, an ARB, or spironolactone, and in patients with chronic kidney disease.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at dpaauw@uw.edu.

References

1. Hernandez RK et al. J Am Geriatr Soc. 2009;57:1997-2003.

2. Park-Wyllie LY et al. PLoS Med. 2009;6:e1000157.

3. Gill SS et al. Arch Intern Med 2009;169:867-73.

4. Peters KR. J Am Geriatr Soc. 2013 Jul;61(7):1170-4.

5. Antoniou TN et al. Arch Intern Med. 2010;170(12):1045-9.

6. Fralick M et al. BMJ. 2014 Oct 30;349:g6196.

7. Glasheen JJ et al. J Gen Intern Med. 2005 Jul;20(7):653-6.

Untreated hearing loss increases dementia risk in middle-aged and older adults, new research confirms. A large observational study from the United Kingdom showed a 42% increased risk for dementia in people with hearing loss compared with their peers with no hearing trouble. In addition, there was no increased risk in those with hearing loss who used hearing aids.

“The evidence is building that hearing loss may be the most impactful modifiable risk factor for dementia in mid-life, but the effectiveness of hearing aid use on reducing the risk of dementia in the real world has remained unclear,” Dongshan Zhu, PhD, with Shandong University, Jinan, China, said in a news release.

“Our study provides the best evidence to date to suggest that hearing aids could be a minimally invasive, cost-effective treatment to mitigate the potential impact of hearing loss on dementia,” Dr. Zhu said.

The study, which was published online in Lancet Public Health, comes on the heels of the 2020 Lancet Commission report on dementia, which suggested hearing loss may be linked to approximately 8% of worldwide dementia cases.
 

‘Compelling’ evidence

For the study, investigators analyzed longitudinal data on 437,704 individuals, most of whom were White, from the UK Biobank (54% female; mean age at baseline, 56 years). Roughly three quarters of the cohort had no hearing loss and one quarter had some level of hearing loss, with 12% of these individuals using hearing aids.

After the researchers controlled for relevant cofactors, compared with people without hearing loss, those with hearing loss who were not using hearing aids had an increased risk for all-cause dementia (hazard ratio [HR], 1.42; 95% confidence interval [CI], 1.29-1.56).

No increased risk was seen in people with hearing loss who were using hearing aids (HR, 1.04; 95% CI, 0.98-1.10).

The positive association of hearing aid use was observed in all-cause dementia and cause-specific dementia subtypes, including Alzheimer’s disease, vascular dementia, and non–Alzheimer’s disease nonvascular dementia.

The data also suggest that the protection against dementia conferred by hearing aid use most likely stems from direct effects from hearing aids rather than indirect mediators, such as social isolation, loneliness, and low mood.

Dr. Zhu said the findings highlight the “urgent need” for the early use of hearing aids when an individual starts having trouble hearing.

“A group effort from across society is necessary, including raising awareness of hearing loss and the potential links with dementia; increasing accessibility to hearing aids by reducing cost; and more support for primary care workers to screen for hearing impairment, raise awareness, and deliver treatment such as fitting hearing aids,” Dr. Zhu said.

Writing in a linked comment, Gill Livingston, MD, and Sergi Costafreda, MD, PhD, with University College London, noted that with addition of this study, “the evidence that hearing aids are a powerful tool to reduce the risk of dementia in people with hearing loss, is as good as possible without randomized controlled trials, which might not be practically possible or ethical because people with hearing loss should not be stopped from using effective treatments.”

“The evidence is compelling that treating hearing loss is a promising way of reducing dementia risk. This is the time to increase awareness of and detection of hearing loss, as well as the acceptability and usability of hearing aids,” Dr. Livingston and Dr. Costafreda added.
 

High-quality evidence – with caveats

Several experts offered perspective on the analysis in a statement from the U.K.-based nonprofit Science Media Centre, which was not involved with the conduct of this study. Charles Marshall, MRCP, PhD, with Queen Mary University of London, said that the study provides “high-quality evidence” that those with hearing loss who use hearing aids are at lower risk for dementia than are those with hearing loss who do not use hearing aids.

“This raises the possibility that a proportion of dementia cases could be prevented by using hearing aids to correct hearing loss. However, the observational nature of this study makes it difficult to be sure that hearing aids are actually causing the reduced risk of dementia,” Dr. Marshall added.

“Hearing aids produce slightly distorted sound, and the brain has to adapt to this in order for hearing aids to be helpful,” he said. “People who are at risk of developing dementia in the future may have early changes in their brain that impair this adaptation, and this may lead to them choosing to not use hearing aids. This would confound the association, creating the appearance that hearing aids were reducing dementia risk, when actually their use was just identifying people with relatively healthy brains,” Dr. Marshall added.

Tara Spires-Jones, PhD, with the University of Edinburgh, said this “well-conducted” study confirms previous similar studies showing an association between hearing loss and dementia risk.

Echoing Dr. Marshall, Dr. Spires-Jones noted that this type of study cannot prove conclusively that hearing loss causes dementia.

“For example,” she said, “it is possible that people who are already in the very early stages of disease are less likely to seek help for hearing loss. However, on balance, this study and the rest of the data in the field indicate that keeping your brain healthy and engaged reduces dementia risk.”

Dr. Spires-Jones said that she agrees with the investigators that it’s “important to help people with hearing loss to get effective hearing aids to help keep their brains engaged through allowing richer social interactions.”

This study was funded by the National Natural Science Foundation of China and Shandong Province, Taishan Scholars Project, China Medical Board, and China Postdoctoral Science Foundation. Dr. Zhu, Dr. Livingston, Dr. Costafreda, Dr. Marshall, and Dr. Spires-Jones have no relevant disclosures.
 

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

Untreated hearing loss increases dementia risk in middle-aged and older adults, new research confirms. A large observational study from the United Kingdom showed a 42% increased risk for dementia in people with hearing loss compared with their peers with no hearing trouble. In addition, there was no increased risk in those with hearing loss who used hearing aids.

“The evidence is building that hearing loss may be the most impactful modifiable risk factor for dementia in mid-life, but the effectiveness of hearing aid use on reducing the risk of dementia in the real world has remained unclear,” Dongshan Zhu, PhD, with Shandong University, Jinan, China, said in a news release.

“Our study provides the best evidence to date to suggest that hearing aids could be a minimally invasive, cost-effective treatment to mitigate the potential impact of hearing loss on dementia,” Dr. Zhu said.

The study, which was published online in Lancet Public Health, comes on the heels of the 2020 Lancet Commission report on dementia, which suggested hearing loss may be linked to approximately 8% of worldwide dementia cases.
 

‘Compelling’ evidence

For the study, investigators analyzed longitudinal data on 437,704 individuals, most of whom were White, from the UK Biobank (54% female; mean age at baseline, 56 years). Roughly three quarters of the cohort had no hearing loss and one quarter had some level of hearing loss, with 12% of these individuals using hearing aids.

After the researchers controlled for relevant cofactors, compared with people without hearing loss, those with hearing loss who were not using hearing aids had an increased risk for all-cause dementia (hazard ratio [HR], 1.42; 95% confidence interval [CI], 1.29-1.56).

No increased risk was seen in people with hearing loss who were using hearing aids (HR, 1.04; 95% CI, 0.98-1.10).

The positive association of hearing aid use was observed in all-cause dementia and cause-specific dementia subtypes, including Alzheimer’s disease, vascular dementia, and non–Alzheimer’s disease nonvascular dementia.

The data also suggest that the protection against dementia conferred by hearing aid use most likely stems from direct effects from hearing aids rather than indirect mediators, such as social isolation, loneliness, and low mood.

Dr. Zhu said the findings highlight the “urgent need” for the early use of hearing aids when an individual starts having trouble hearing.

“A group effort from across society is necessary, including raising awareness of hearing loss and the potential links with dementia; increasing accessibility to hearing aids by reducing cost; and more support for primary care workers to screen for hearing impairment, raise awareness, and deliver treatment such as fitting hearing aids,” Dr. Zhu said.

Writing in a linked comment, Gill Livingston, MD, and Sergi Costafreda, MD, PhD, with University College London, noted that with addition of this study, “the evidence that hearing aids are a powerful tool to reduce the risk of dementia in people with hearing loss, is as good as possible without randomized controlled trials, which might not be practically possible or ethical because people with hearing loss should not be stopped from using effective treatments.”

“The evidence is compelling that treating hearing loss is a promising way of reducing dementia risk. This is the time to increase awareness of and detection of hearing loss, as well as the acceptability and usability of hearing aids,” Dr. Livingston and Dr. Costafreda added.
 

High-quality evidence – with caveats

Several experts offered perspective on the analysis in a statement from the U.K.-based nonprofit Science Media Centre, which was not involved with the conduct of this study. Charles Marshall, MRCP, PhD, with Queen Mary University of London, said that the study provides “high-quality evidence” that those with hearing loss who use hearing aids are at lower risk for dementia than are those with hearing loss who do not use hearing aids.

“This raises the possibility that a proportion of dementia cases could be prevented by using hearing aids to correct hearing loss. However, the observational nature of this study makes it difficult to be sure that hearing aids are actually causing the reduced risk of dementia,” Dr. Marshall added.

“Hearing aids produce slightly distorted sound, and the brain has to adapt to this in order for hearing aids to be helpful,” he said. “People who are at risk of developing dementia in the future may have early changes in their brain that impair this adaptation, and this may lead to them choosing to not use hearing aids. This would confound the association, creating the appearance that hearing aids were reducing dementia risk, when actually their use was just identifying people with relatively healthy brains,” Dr. Marshall added.

Tara Spires-Jones, PhD, with the University of Edinburgh, said this “well-conducted” study confirms previous similar studies showing an association between hearing loss and dementia risk.

Echoing Dr. Marshall, Dr. Spires-Jones noted that this type of study cannot prove conclusively that hearing loss causes dementia.

“For example,” she said, “it is possible that people who are already in the very early stages of disease are less likely to seek help for hearing loss. However, on balance, this study and the rest of the data in the field indicate that keeping your brain healthy and engaged reduces dementia risk.”

Dr. Spires-Jones said that she agrees with the investigators that it’s “important to help people with hearing loss to get effective hearing aids to help keep their brains engaged through allowing richer social interactions.”

This study was funded by the National Natural Science Foundation of China and Shandong Province, Taishan Scholars Project, China Medical Board, and China Postdoctoral Science Foundation. Dr. Zhu, Dr. Livingston, Dr. Costafreda, Dr. Marshall, and Dr. Spires-Jones have no relevant disclosures.
 

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

Untreated hearing loss increases dementia risk in middle-aged and older adults, new research confirms. A large observational study from the United Kingdom showed a 42% increased risk for dementia in people with hearing loss compared with their peers with no hearing trouble. In addition, there was no increased risk in those with hearing loss who used hearing aids.

“The evidence is building that hearing loss may be the most impactful modifiable risk factor for dementia in mid-life, but the effectiveness of hearing aid use on reducing the risk of dementia in the real world has remained unclear,” Dongshan Zhu, PhD, with Shandong University, Jinan, China, said in a news release.

“Our study provides the best evidence to date to suggest that hearing aids could be a minimally invasive, cost-effective treatment to mitigate the potential impact of hearing loss on dementia,” Dr. Zhu said.

The study, which was published online in Lancet Public Health, comes on the heels of the 2020 Lancet Commission report on dementia, which suggested hearing loss may be linked to approximately 8% of worldwide dementia cases.
 

‘Compelling’ evidence

For the study, investigators analyzed longitudinal data on 437,704 individuals, most of whom were White, from the UK Biobank (54% female; mean age at baseline, 56 years). Roughly three quarters of the cohort had no hearing loss and one quarter had some level of hearing loss, with 12% of these individuals using hearing aids.

After the researchers controlled for relevant cofactors, compared with people without hearing loss, those with hearing loss who were not using hearing aids had an increased risk for all-cause dementia (hazard ratio [HR], 1.42; 95% confidence interval [CI], 1.29-1.56).

No increased risk was seen in people with hearing loss who were using hearing aids (HR, 1.04; 95% CI, 0.98-1.10).

The positive association of hearing aid use was observed in all-cause dementia and cause-specific dementia subtypes, including Alzheimer’s disease, vascular dementia, and non–Alzheimer’s disease nonvascular dementia.

The data also suggest that the protection against dementia conferred by hearing aid use most likely stems from direct effects from hearing aids rather than indirect mediators, such as social isolation, loneliness, and low mood.

Dr. Zhu said the findings highlight the “urgent need” for the early use of hearing aids when an individual starts having trouble hearing.

“A group effort from across society is necessary, including raising awareness of hearing loss and the potential links with dementia; increasing accessibility to hearing aids by reducing cost; and more support for primary care workers to screen for hearing impairment, raise awareness, and deliver treatment such as fitting hearing aids,” Dr. Zhu said.

Writing in a linked comment, Gill Livingston, MD, and Sergi Costafreda, MD, PhD, with University College London, noted that with addition of this study, “the evidence that hearing aids are a powerful tool to reduce the risk of dementia in people with hearing loss, is as good as possible without randomized controlled trials, which might not be practically possible or ethical because people with hearing loss should not be stopped from using effective treatments.”

“The evidence is compelling that treating hearing loss is a promising way of reducing dementia risk. This is the time to increase awareness of and detection of hearing loss, as well as the acceptability and usability of hearing aids,” Dr. Livingston and Dr. Costafreda added.
 

High-quality evidence – with caveats

Several experts offered perspective on the analysis in a statement from the U.K.-based nonprofit Science Media Centre, which was not involved with the conduct of this study. Charles Marshall, MRCP, PhD, with Queen Mary University of London, said that the study provides “high-quality evidence” that those with hearing loss who use hearing aids are at lower risk for dementia than are those with hearing loss who do not use hearing aids.

“This raises the possibility that a proportion of dementia cases could be prevented by using hearing aids to correct hearing loss. However, the observational nature of this study makes it difficult to be sure that hearing aids are actually causing the reduced risk of dementia,” Dr. Marshall added.

“Hearing aids produce slightly distorted sound, and the brain has to adapt to this in order for hearing aids to be helpful,” he said. “People who are at risk of developing dementia in the future may have early changes in their brain that impair this adaptation, and this may lead to them choosing to not use hearing aids. This would confound the association, creating the appearance that hearing aids were reducing dementia risk, when actually their use was just identifying people with relatively healthy brains,” Dr. Marshall added.

Tara Spires-Jones, PhD, with the University of Edinburgh, said this “well-conducted” study confirms previous similar studies showing an association between hearing loss and dementia risk.

Echoing Dr. Marshall, Dr. Spires-Jones noted that this type of study cannot prove conclusively that hearing loss causes dementia.

“For example,” she said, “it is possible that people who are already in the very early stages of disease are less likely to seek help for hearing loss. However, on balance, this study and the rest of the data in the field indicate that keeping your brain healthy and engaged reduces dementia risk.”

Dr. Spires-Jones said that she agrees with the investigators that it’s “important to help people with hearing loss to get effective hearing aids to help keep their brains engaged through allowing richer social interactions.”

This study was funded by the National Natural Science Foundation of China and Shandong Province, Taishan Scholars Project, China Medical Board, and China Postdoctoral Science Foundation. Dr. Zhu, Dr. Livingston, Dr. Costafreda, Dr. Marshall, and Dr. Spires-Jones have no relevant disclosures.
 

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

BOSTON – Older women who have had breast cancer frequently undergo annual surveillance mammography, even if there is only a small risk of their developing a second cancer or if they have other mortality risks associated with age and comorbidities. This ongoing annual surveillance with mammography may be doing more harm than good, warn researchers.

In a study that included almost 45,000 women who were aged 67 years or older when they were diagnosed with breast cancer, investigators found that patients commonly underwent annual mammographies.

“Even 10 years after their initial diagnosis ... about 40% of them were still getting surveillance mammography well into their 80s and 90s,” noted lead investigator Elizabeth Berger, MD, assistant professor of breast surgical oncology, Yale University, New Haven, Conn.

“Ongoing surveillance mammography in these patients may lead to overdiagnosis and overtreatment of cancers that potentially would not harm patients if left untreated,” Dr. Berger said.

“A positive or false positive finding may unnecessarily erode patient quality of life and incur costs to the patient and health care system without benefit,” she said. She added: “If an elderly woman is in poor health and has significant competing mortality risks compared to breast cancer, annual mammography may not be necessary.”

The research was presented at the annual meeting of the American Society of Breast Surgeons (ASBrS). The study was highlighted in a preview press briefing.

Speaking at the press briefing, Dr. Berger said that the “risks and benefits of surveillance mammography, including its downstream effects, should be considered by both patients and their doctors together to create a shared decision plan.” She acknowledged that the idea of skipping mammograms may be a sensitive one for patients.

She also shared what she described as “exciting news”: “We have just recently received funding from our geriatric group here at Yale to start to evaluate the potential benefits and harms of these surveillance mammographies.”

The aim is to evaluate false positive rates and the potential for overdiagnosis and overtreatment, “so stay tuned,” she added.

Approached for comment, Mediget Teshome, MD, MPH, said it was “not surprising to see the high rates of surveillance mammography, especially in the short term after treatment.”

She said in an interview that the results suggest that it “may be being overused,” given the low rates of second primary breast cancer and the “competing health concerns” of these women.

Overuse can, on the other hand, “definitely be a complex issue,” said Dr. Teshome, associate professor, department of breast surgical oncology, University of Texas MD Anderson Cancer Center, Houston.

“The goal of mammography screening is to identify breast cancer at an early stage,” she explained. She noted that because of the “competing mortality risk from other challenging and life-threatening health problems,” early-stage breast cancer “may not contribute significantly” to the overall mortality risk.

“In general, in this patient population, consideration should be given to stratifying based on an individual patient’s risk of breast cancer recurrence or new breast cancer, estimated life expectancy, as well as shared decision-making with the patient based on their goals of care.”
 

Study details

To examine the use of surveillance mammography and the risk of subsequent cancers among older women, Dr. Berger and her team used data from the Surveillance, Epidemiology, and End Results (SEER) registry to identify women aged 67 years or older who were diagnosed with a first nonmetastatic beast cancer between 2003 and 2007.

The patients were followed beginning 1 year after diagnosis until the occurrence of a second primary breast cancer, death, or the end of follow-up in 2017.

Data on 44,475 women were analyzed. Of those patients, 30% were older than 80 years. The majority (74%) of breast cancers were of stage I or II, and 72% were hormone receptor–positive (HR+).

Comorbid conditions were common; 55% of women had at least one, and 16% had three or more.

Life expectancy, determined on the basis of age, sex, and comorbidities, was estimated at less than 5 years for 26% of women. For 36% of patients, life expectancy was 6-10 years, and for 38%, it was longer than 10 years.

The cumulative incidence of developing a second primary breast cancer varied by life expectancy and the tumor’s molecular subtype.

The incidence was 3.7% among women with a life expectancy of less than 5 years, 4.9% among those expected to live 6-10 years, and 7.6% among those predicted to live more than 10 years.

Among women with a life expectancy of less than 5 years, the cumulative incidence of a second primary tumor was 4.0% among those with triple-negative breast cancer, vs. 3.0% among those with HR+ breast cancer.

Among patients whose life expectancy was more than 10 years, the cumulative incidence of a second primary tumor was 9.2% among women with triple-negative disease, vs. 7.0% among those with HR+ cancers.

The team found that it was common for women across all the groups to undergo mammography.

Among women with a life expectancy of 6-10 years, 82% underwent at least one mammogram, and 65% underwent five mammograms. Even among women with a life expectancy of less than 1 year, 51% underwent at least one mammogram within 12 months of death.

Among women with a life expectancy of less than 5 years, 68% of women had received a mammogram 1 year after treatment; 53% underwent three mammograms within 3 years after treatment.

No funding for the study was declared. The investigators have disclosed no relevant financial relationships.

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

BOSTON – Older women who have had breast cancer frequently undergo annual surveillance mammography, even if there is only a small risk of their developing a second cancer or if they have other mortality risks associated with age and comorbidities. This ongoing annual surveillance with mammography may be doing more harm than good, warn researchers.

In a study that included almost 45,000 women who were aged 67 years or older when they were diagnosed with breast cancer, investigators found that patients commonly underwent annual mammographies.

“Even 10 years after their initial diagnosis ... about 40% of them were still getting surveillance mammography well into their 80s and 90s,” noted lead investigator Elizabeth Berger, MD, assistant professor of breast surgical oncology, Yale University, New Haven, Conn.

“Ongoing surveillance mammography in these patients may lead to overdiagnosis and overtreatment of cancers that potentially would not harm patients if left untreated,” Dr. Berger said.

“A positive or false positive finding may unnecessarily erode patient quality of life and incur costs to the patient and health care system without benefit,” she said. She added: “If an elderly woman is in poor health and has significant competing mortality risks compared to breast cancer, annual mammography may not be necessary.”

The research was presented at the annual meeting of the American Society of Breast Surgeons (ASBrS). The study was highlighted in a preview press briefing.

Speaking at the press briefing, Dr. Berger said that the “risks and benefits of surveillance mammography, including its downstream effects, should be considered by both patients and their doctors together to create a shared decision plan.” She acknowledged that the idea of skipping mammograms may be a sensitive one for patients.

She also shared what she described as “exciting news”: “We have just recently received funding from our geriatric group here at Yale to start to evaluate the potential benefits and harms of these surveillance mammographies.”

The aim is to evaluate false positive rates and the potential for overdiagnosis and overtreatment, “so stay tuned,” she added.

Approached for comment, Mediget Teshome, MD, MPH, said it was “not surprising to see the high rates of surveillance mammography, especially in the short term after treatment.”

She said in an interview that the results suggest that it “may be being overused,” given the low rates of second primary breast cancer and the “competing health concerns” of these women.

Overuse can, on the other hand, “definitely be a complex issue,” said Dr. Teshome, associate professor, department of breast surgical oncology, University of Texas MD Anderson Cancer Center, Houston.

“The goal of mammography screening is to identify breast cancer at an early stage,” she explained. She noted that because of the “competing mortality risk from other challenging and life-threatening health problems,” early-stage breast cancer “may not contribute significantly” to the overall mortality risk.

“In general, in this patient population, consideration should be given to stratifying based on an individual patient’s risk of breast cancer recurrence or new breast cancer, estimated life expectancy, as well as shared decision-making with the patient based on their goals of care.”
 

Study details

To examine the use of surveillance mammography and the risk of subsequent cancers among older women, Dr. Berger and her team used data from the Surveillance, Epidemiology, and End Results (SEER) registry to identify women aged 67 years or older who were diagnosed with a first nonmetastatic beast cancer between 2003 and 2007.

The patients were followed beginning 1 year after diagnosis until the occurrence of a second primary breast cancer, death, or the end of follow-up in 2017.

Data on 44,475 women were analyzed. Of those patients, 30% were older than 80 years. The majority (74%) of breast cancers were of stage I or II, and 72% were hormone receptor–positive (HR+).

Comorbid conditions were common; 55% of women had at least one, and 16% had three or more.

Life expectancy, determined on the basis of age, sex, and comorbidities, was estimated at less than 5 years for 26% of women. For 36% of patients, life expectancy was 6-10 years, and for 38%, it was longer than 10 years.

The cumulative incidence of developing a second primary breast cancer varied by life expectancy and the tumor’s molecular subtype.

The incidence was 3.7% among women with a life expectancy of less than 5 years, 4.9% among those expected to live 6-10 years, and 7.6% among those predicted to live more than 10 years.

Among women with a life expectancy of less than 5 years, the cumulative incidence of a second primary tumor was 4.0% among those with triple-negative breast cancer, vs. 3.0% among those with HR+ breast cancer.

Among patients whose life expectancy was more than 10 years, the cumulative incidence of a second primary tumor was 9.2% among women with triple-negative disease, vs. 7.0% among those with HR+ cancers.

The team found that it was common for women across all the groups to undergo mammography.

Among women with a life expectancy of 6-10 years, 82% underwent at least one mammogram, and 65% underwent five mammograms. Even among women with a life expectancy of less than 1 year, 51% underwent at least one mammogram within 12 months of death.

Among women with a life expectancy of less than 5 years, 68% of women had received a mammogram 1 year after treatment; 53% underwent three mammograms within 3 years after treatment.

No funding for the study was declared. The investigators have disclosed no relevant financial relationships.

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

BOSTON – Older women who have had breast cancer frequently undergo annual surveillance mammography, even if there is only a small risk of their developing a second cancer or if they have other mortality risks associated with age and comorbidities. This ongoing annual surveillance with mammography may be doing more harm than good, warn researchers.

In a study that included almost 45,000 women who were aged 67 years or older when they were diagnosed with breast cancer, investigators found that patients commonly underwent annual mammographies.

“Even 10 years after their initial diagnosis ... about 40% of them were still getting surveillance mammography well into their 80s and 90s,” noted lead investigator Elizabeth Berger, MD, assistant professor of breast surgical oncology, Yale University, New Haven, Conn.

“Ongoing surveillance mammography in these patients may lead to overdiagnosis and overtreatment of cancers that potentially would not harm patients if left untreated,” Dr. Berger said.

“A positive or false positive finding may unnecessarily erode patient quality of life and incur costs to the patient and health care system without benefit,” she said. She added: “If an elderly woman is in poor health and has significant competing mortality risks compared to breast cancer, annual mammography may not be necessary.”

The research was presented at the annual meeting of the American Society of Breast Surgeons (ASBrS). The study was highlighted in a preview press briefing.

Speaking at the press briefing, Dr. Berger said that the “risks and benefits of surveillance mammography, including its downstream effects, should be considered by both patients and their doctors together to create a shared decision plan.” She acknowledged that the idea of skipping mammograms may be a sensitive one for patients.

She also shared what she described as “exciting news”: “We have just recently received funding from our geriatric group here at Yale to start to evaluate the potential benefits and harms of these surveillance mammographies.”

The aim is to evaluate false positive rates and the potential for overdiagnosis and overtreatment, “so stay tuned,” she added.

Approached for comment, Mediget Teshome, MD, MPH, said it was “not surprising to see the high rates of surveillance mammography, especially in the short term after treatment.”

She said in an interview that the results suggest that it “may be being overused,” given the low rates of second primary breast cancer and the “competing health concerns” of these women.

Overuse can, on the other hand, “definitely be a complex issue,” said Dr. Teshome, associate professor, department of breast surgical oncology, University of Texas MD Anderson Cancer Center, Houston.

“The goal of mammography screening is to identify breast cancer at an early stage,” she explained. She noted that because of the “competing mortality risk from other challenging and life-threatening health problems,” early-stage breast cancer “may not contribute significantly” to the overall mortality risk.

“In general, in this patient population, consideration should be given to stratifying based on an individual patient’s risk of breast cancer recurrence or new breast cancer, estimated life expectancy, as well as shared decision-making with the patient based on their goals of care.”
 

Study details

To examine the use of surveillance mammography and the risk of subsequent cancers among older women, Dr. Berger and her team used data from the Surveillance, Epidemiology, and End Results (SEER) registry to identify women aged 67 years or older who were diagnosed with a first nonmetastatic beast cancer between 2003 and 2007.

The patients were followed beginning 1 year after diagnosis until the occurrence of a second primary breast cancer, death, or the end of follow-up in 2017.

Data on 44,475 women were analyzed. Of those patients, 30% were older than 80 years. The majority (74%) of breast cancers were of stage I or II, and 72% were hormone receptor–positive (HR+).

Comorbid conditions were common; 55% of women had at least one, and 16% had three or more.

Life expectancy, determined on the basis of age, sex, and comorbidities, was estimated at less than 5 years for 26% of women. For 36% of patients, life expectancy was 6-10 years, and for 38%, it was longer than 10 years.

The cumulative incidence of developing a second primary breast cancer varied by life expectancy and the tumor’s molecular subtype.

The incidence was 3.7% among women with a life expectancy of less than 5 years, 4.9% among those expected to live 6-10 years, and 7.6% among those predicted to live more than 10 years.

Among women with a life expectancy of less than 5 years, the cumulative incidence of a second primary tumor was 4.0% among those with triple-negative breast cancer, vs. 3.0% among those with HR+ breast cancer.

Among patients whose life expectancy was more than 10 years, the cumulative incidence of a second primary tumor was 9.2% among women with triple-negative disease, vs. 7.0% among those with HR+ cancers.

The team found that it was common for women across all the groups to undergo mammography.

Among women with a life expectancy of 6-10 years, 82% underwent at least one mammogram, and 65% underwent five mammograms. Even among women with a life expectancy of less than 1 year, 51% underwent at least one mammogram within 12 months of death.

Among women with a life expectancy of less than 5 years, 68% of women had received a mammogram 1 year after treatment; 53% underwent three mammograms within 3 years after treatment.

No funding for the study was declared. The investigators have disclosed no relevant financial relationships.

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

Older women with high levels of physical activity showed twice the risk of atrial fibrillation (AFib) over 10 years as they did for cardiac disease or stroke, based on data from 46 cross-country skiers.

Although previous research suggests that women derive greater health benefits from endurance sports, compared with men, women are generally underrepresented in sports cardiology research, and most previous studies have focused on younger women, Marius Myrstad, MD, of Baerum Hospital, Gjettum, Norway, said in a presentation at the annual congress of the European Association of Preventive Cardiology.

Previous research also has shown an increased risk of AFib in male endurance athletes, but similar data on women are lacking, Dr. Myrstad said.

The researchers reviewed data from the Birkebeiner Ageing Study, a study of Norwegian cross-country skiers aged 65 years and older who were followed for 10 years. The participants were competitors in the 2009/2010 Birkebeiner race, a 54-km cross country ski race in Norway.

Participants responded to a questionnaire addressing cardiovascular disease risk factors, exercise habits, and other health issues. The mean age at baseline was 67.5 year. A total of 34 participants (76%) were available for follow-up visits in 2014, and 36 attended a follow-up visit in 2020. Cumulative exposure to exercise was 26 years.

A total of 86% of the women reported moderate to vigorous exercise in the past year at baseline; 61% did so at the 2020 follow-up visit. One of the participants died during the study period.

“The baseline prevalence of cardiovascular conditions was very low,” Dr. Myrstad noted.

However, despite a low prevalence of cardiovascular risk factors, the risk of AFib in the study population was twice as high as for other cardiac diseases and stroke (15.6%, 7.1%, and 7.1%, respectively).

The mechanism of action for the increased AFib remains unclear, but the current study highlights the need for large, prospective studies of female athletes to address not only AFib, but also exercise-induced cardiac remodeling and cardiovascular health in general, said Dr. Myrstad.

The findings were limited by the small sample size and use of self-reports, Dr. Myrstad said, and more research is needed to clarify the association between increased AFib and high-level athletic activity in women.

“We should strive to close the gap between female and male athletes in sports cardiology research,” he added.

Consider the big picture of AFib risk

This study is important because of the growing recognition that atrial fibrillation may be a preventable disease, said Gregory Marcus, MD, a cardiologist at the University of California, San Francisco, said in an interview.

American Heart Association

“Various behaviors or exposures that are under the control of the individual patient may reveal especially powerful means to help reduce risk,” he added.

Dr. Marcus said he was not surprised by the current study findings, as they reflect those of other studies suggesting a heightened risk for atrial fibrillation associated with very excessive exercise. However, the study was limited by the relatively small size and lack of a comparison group, he said. In addition, “The study was observational, and therefore the possibility that factors other than the predictor of interest, in this case intensive endurance exercise, were truly causal of atrial fibrillation could not be excluded,” he noted.

“It is very important to place this specialized analysis in the greater context of the full weight of evidence related to physical activity and atrial fibrillation,” said Dr. Marcus. “Specifically, when it comes to the general public and the great majority of patients we see in clinical practice, encouraging more physical activity is generally the best approach to reduce risks of atrial fibrillation,” he said. “It appears to be only in extraordinarily rigorous and prolonged endurance exercise that higher risks of atrial fibrillation may result,” he noted.

However, “Exercise also has many other benefits, related to overall cardiovascular health, brain health, bone health, and even cancer risk reduction, such that, even among the highly trained endurance athletes, the net benefit versus risk remains unknown,” he said. 

“While the risk of atrial fibrillation in these highly trained endurance athletes was higher than expected, it still occurred in the minority,” Dr. Marcus said. “Therefore, there are certainly other factors yet to be identified that influence this heightened atrial fibrillation risk, and future research aimed at elucidating these other factors may help identify individuals more or less prone to atrial fibrillation or other behaviors that can help mitigate that risk.”

Dr. Myrstad disclosed lecture fees from Bayer, Boehringer-Ingelheim, Bristol Myers Squibb, MSD, and Pfizer unrelated to the current study. Dr. Marcus disclosed serving as a consultant for Johnson and Johnson and InCarda, and holding equity as a cofounder of InCarda.

Older women with high levels of physical activity showed twice the risk of atrial fibrillation (AFib) over 10 years as they did for cardiac disease or stroke, based on data from 46 cross-country skiers.

Although previous research suggests that women derive greater health benefits from endurance sports, compared with men, women are generally underrepresented in sports cardiology research, and most previous studies have focused on younger women, Marius Myrstad, MD, of Baerum Hospital, Gjettum, Norway, said in a presentation at the annual congress of the European Association of Preventive Cardiology.

Previous research also has shown an increased risk of AFib in male endurance athletes, but similar data on women are lacking, Dr. Myrstad said.

The researchers reviewed data from the Birkebeiner Ageing Study, a study of Norwegian cross-country skiers aged 65 years and older who were followed for 10 years. The participants were competitors in the 2009/2010 Birkebeiner race, a 54-km cross country ski race in Norway.

Participants responded to a questionnaire addressing cardiovascular disease risk factors, exercise habits, and other health issues. The mean age at baseline was 67.5 year. A total of 34 participants (76%) were available for follow-up visits in 2014, and 36 attended a follow-up visit in 2020. Cumulative exposure to exercise was 26 years.

A total of 86% of the women reported moderate to vigorous exercise in the past year at baseline; 61% did so at the 2020 follow-up visit. One of the participants died during the study period.

“The baseline prevalence of cardiovascular conditions was very low,” Dr. Myrstad noted.

However, despite a low prevalence of cardiovascular risk factors, the risk of AFib in the study population was twice as high as for other cardiac diseases and stroke (15.6%, 7.1%, and 7.1%, respectively).

The mechanism of action for the increased AFib remains unclear, but the current study highlights the need for large, prospective studies of female athletes to address not only AFib, but also exercise-induced cardiac remodeling and cardiovascular health in general, said Dr. Myrstad.

The findings were limited by the small sample size and use of self-reports, Dr. Myrstad said, and more research is needed to clarify the association between increased AFib and high-level athletic activity in women.

“We should strive to close the gap between female and male athletes in sports cardiology research,” he added.

Consider the big picture of AFib risk

This study is important because of the growing recognition that atrial fibrillation may be a preventable disease, said Gregory Marcus, MD, a cardiologist at the University of California, San Francisco, said in an interview.

American Heart Association

“Various behaviors or exposures that are under the control of the individual patient may reveal especially powerful means to help reduce risk,” he added.

Dr. Marcus said he was not surprised by the current study findings, as they reflect those of other studies suggesting a heightened risk for atrial fibrillation associated with very excessive exercise. However, the study was limited by the relatively small size and lack of a comparison group, he said. In addition, “The study was observational, and therefore the possibility that factors other than the predictor of interest, in this case intensive endurance exercise, were truly causal of atrial fibrillation could not be excluded,” he noted.

“It is very important to place this specialized analysis in the greater context of the full weight of evidence related to physical activity and atrial fibrillation,” said Dr. Marcus. “Specifically, when it comes to the general public and the great majority of patients we see in clinical practice, encouraging more physical activity is generally the best approach to reduce risks of atrial fibrillation,” he said. “It appears to be only in extraordinarily rigorous and prolonged endurance exercise that higher risks of atrial fibrillation may result,” he noted.

However, “Exercise also has many other benefits, related to overall cardiovascular health, brain health, bone health, and even cancer risk reduction, such that, even among the highly trained endurance athletes, the net benefit versus risk remains unknown,” he said. 

“While the risk of atrial fibrillation in these highly trained endurance athletes was higher than expected, it still occurred in the minority,” Dr. Marcus said. “Therefore, there are certainly other factors yet to be identified that influence this heightened atrial fibrillation risk, and future research aimed at elucidating these other factors may help identify individuals more or less prone to atrial fibrillation or other behaviors that can help mitigate that risk.”

Dr. Myrstad disclosed lecture fees from Bayer, Boehringer-Ingelheim, Bristol Myers Squibb, MSD, and Pfizer unrelated to the current study. Dr. Marcus disclosed serving as a consultant for Johnson and Johnson and InCarda, and holding equity as a cofounder of InCarda.

Older women with high levels of physical activity showed twice the risk of atrial fibrillation (AFib) over 10 years as they did for cardiac disease or stroke, based on data from 46 cross-country skiers.

Although previous research suggests that women derive greater health benefits from endurance sports, compared with men, women are generally underrepresented in sports cardiology research, and most previous studies have focused on younger women, Marius Myrstad, MD, of Baerum Hospital, Gjettum, Norway, said in a presentation at the annual congress of the European Association of Preventive Cardiology.

Previous research also has shown an increased risk of AFib in male endurance athletes, but similar data on women are lacking, Dr. Myrstad said.

The researchers reviewed data from the Birkebeiner Ageing Study, a study of Norwegian cross-country skiers aged 65 years and older who were followed for 10 years. The participants were competitors in the 2009/2010 Birkebeiner race, a 54-km cross country ski race in Norway.

Participants responded to a questionnaire addressing cardiovascular disease risk factors, exercise habits, and other health issues. The mean age at baseline was 67.5 year. A total of 34 participants (76%) were available for follow-up visits in 2014, and 36 attended a follow-up visit in 2020. Cumulative exposure to exercise was 26 years.

A total of 86% of the women reported moderate to vigorous exercise in the past year at baseline; 61% did so at the 2020 follow-up visit. One of the participants died during the study period.

“The baseline prevalence of cardiovascular conditions was very low,” Dr. Myrstad noted.

However, despite a low prevalence of cardiovascular risk factors, the risk of AFib in the study population was twice as high as for other cardiac diseases and stroke (15.6%, 7.1%, and 7.1%, respectively).

The mechanism of action for the increased AFib remains unclear, but the current study highlights the need for large, prospective studies of female athletes to address not only AFib, but also exercise-induced cardiac remodeling and cardiovascular health in general, said Dr. Myrstad.

The findings were limited by the small sample size and use of self-reports, Dr. Myrstad said, and more research is needed to clarify the association between increased AFib and high-level athletic activity in women.

“We should strive to close the gap between female and male athletes in sports cardiology research,” he added.

Consider the big picture of AFib risk

This study is important because of the growing recognition that atrial fibrillation may be a preventable disease, said Gregory Marcus, MD, a cardiologist at the University of California, San Francisco, said in an interview.

American Heart Association

“Various behaviors or exposures that are under the control of the individual patient may reveal especially powerful means to help reduce risk,” he added.

Dr. Marcus said he was not surprised by the current study findings, as they reflect those of other studies suggesting a heightened risk for atrial fibrillation associated with very excessive exercise. However, the study was limited by the relatively small size and lack of a comparison group, he said. In addition, “The study was observational, and therefore the possibility that factors other than the predictor of interest, in this case intensive endurance exercise, were truly causal of atrial fibrillation could not be excluded,” he noted.

“It is very important to place this specialized analysis in the greater context of the full weight of evidence related to physical activity and atrial fibrillation,” said Dr. Marcus. “Specifically, when it comes to the general public and the great majority of patients we see in clinical practice, encouraging more physical activity is generally the best approach to reduce risks of atrial fibrillation,” he said. “It appears to be only in extraordinarily rigorous and prolonged endurance exercise that higher risks of atrial fibrillation may result,” he noted.

However, “Exercise also has many other benefits, related to overall cardiovascular health, brain health, bone health, and even cancer risk reduction, such that, even among the highly trained endurance athletes, the net benefit versus risk remains unknown,” he said. 

“While the risk of atrial fibrillation in these highly trained endurance athletes was higher than expected, it still occurred in the minority,” Dr. Marcus said. “Therefore, there are certainly other factors yet to be identified that influence this heightened atrial fibrillation risk, and future research aimed at elucidating these other factors may help identify individuals more or less prone to atrial fibrillation or other behaviors that can help mitigate that risk.”

Dr. Myrstad disclosed lecture fees from Bayer, Boehringer-Ingelheim, Bristol Myers Squibb, MSD, and Pfizer unrelated to the current study. Dr. Marcus disclosed serving as a consultant for Johnson and Johnson and InCarda, and holding equity as a cofounder of InCarda.

The U.S. Food and Drug Administration (FDA) has approved the first vaccine for respiratory syncytial virus (RSV) in the United States, the agency announced May 3. Arexvy, manufactured by GSK, is the world’s first RSV vaccine for adults aged 60 years and older,the company said in an announcement.

Every year, RSV is responsible for 60,000–120,000 hospitalizations and 6,000–10,000 deaths among U.S. adults older than age, according to the FDA. Older adults with underlying health conditions — such as diabetes, a weakened immune system, or lung or heart disease — are at high risk for severe disease. "Today’s approval of the first RSV vaccine is an important public health achievement to prevent a disease which can be life-threatening and reflects the FDA’s continued commitment to facilitating the development of safe and effective vaccines for use in the United States," said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, in a statement.

The FDA approval of Arexvy was based on a clinical study of approximately 25,000 patients. Half of these patients received Arexvy, while the other half received a placebo. Researchers found that the RSV vaccine reduced RSV-associated lower respiratory tract disease (LRTD) by nearly 83% and reduced the risk of developing severe RSV-associated LRTD by 94%. The most commonly reported side effects were injection site pain, fatigue, muscle pain, headache, and joint stiffness/pain. Ten patients who received Arexvy and four patients who received placebo experienced atrial fibrillation within 30 days of vaccination. The company is planning to assess risk for atrial fibrillation in postmarking studies, the FDA said. The European Medicine Agency’s Committee for Medicinal Products for Human Use recommended approval of Arexvy on April 25, 2023, on the basis of data from the same clinical trial.

GSK said that the U.S. launch of Arexvy will occur sometime in the fall before the 2023/2024 RSV season, but the company did not provide exact dates. "Today marks a turning point in our effort to reduce the significant burden of RSV," said GSK’s chief scientific officer, Tony Wood, PhD, in a company statement. "Our focus now is to ensure eligible older adults in the U.S. can access the vaccine as quickly as possible and to progress regulatory review in other countries."

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

The U.S. Food and Drug Administration (FDA) has approved the first vaccine for respiratory syncytial virus (RSV) in the United States, the agency announced May 3. Arexvy, manufactured by GSK, is the world’s first RSV vaccine for adults aged 60 years and older,the company said in an announcement.

Every year, RSV is responsible for 60,000–120,000 hospitalizations and 6,000–10,000 deaths among U.S. adults older than age, according to the FDA. Older adults with underlying health conditions — such as diabetes, a weakened immune system, or lung or heart disease — are at high risk for severe disease. "Today’s approval of the first RSV vaccine is an important public health achievement to prevent a disease which can be life-threatening and reflects the FDA’s continued commitment to facilitating the development of safe and effective vaccines for use in the United States," said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, in a statement.

The FDA approval of Arexvy was based on a clinical study of approximately 25,000 patients. Half of these patients received Arexvy, while the other half received a placebo. Researchers found that the RSV vaccine reduced RSV-associated lower respiratory tract disease (LRTD) by nearly 83% and reduced the risk of developing severe RSV-associated LRTD by 94%. The most commonly reported side effects were injection site pain, fatigue, muscle pain, headache, and joint stiffness/pain. Ten patients who received Arexvy and four patients who received placebo experienced atrial fibrillation within 30 days of vaccination. The company is planning to assess risk for atrial fibrillation in postmarking studies, the FDA said. The European Medicine Agency’s Committee for Medicinal Products for Human Use recommended approval of Arexvy on April 25, 2023, on the basis of data from the same clinical trial.

GSK said that the U.S. launch of Arexvy will occur sometime in the fall before the 2023/2024 RSV season, but the company did not provide exact dates. "Today marks a turning point in our effort to reduce the significant burden of RSV," said GSK’s chief scientific officer, Tony Wood, PhD, in a company statement. "Our focus now is to ensure eligible older adults in the U.S. can access the vaccine as quickly as possible and to progress regulatory review in other countries."

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

The U.S. Food and Drug Administration (FDA) has approved the first vaccine for respiratory syncytial virus (RSV) in the United States, the agency announced May 3. Arexvy, manufactured by GSK, is the world’s first RSV vaccine for adults aged 60 years and older,the company said in an announcement.

Every year, RSV is responsible for 60,000–120,000 hospitalizations and 6,000–10,000 deaths among U.S. adults older than age, according to the FDA. Older adults with underlying health conditions — such as diabetes, a weakened immune system, or lung or heart disease — are at high risk for severe disease. "Today’s approval of the first RSV vaccine is an important public health achievement to prevent a disease which can be life-threatening and reflects the FDA’s continued commitment to facilitating the development of safe and effective vaccines for use in the United States," said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, in a statement.

The FDA approval of Arexvy was based on a clinical study of approximately 25,000 patients. Half of these patients received Arexvy, while the other half received a placebo. Researchers found that the RSV vaccine reduced RSV-associated lower respiratory tract disease (LRTD) by nearly 83% and reduced the risk of developing severe RSV-associated LRTD by 94%. The most commonly reported side effects were injection site pain, fatigue, muscle pain, headache, and joint stiffness/pain. Ten patients who received Arexvy and four patients who received placebo experienced atrial fibrillation within 30 days of vaccination. The company is planning to assess risk for atrial fibrillation in postmarking studies, the FDA said. The European Medicine Agency’s Committee for Medicinal Products for Human Use recommended approval of Arexvy on April 25, 2023, on the basis of data from the same clinical trial.

GSK said that the U.S. launch of Arexvy will occur sometime in the fall before the 2023/2024 RSV season, but the company did not provide exact dates. "Today marks a turning point in our effort to reduce the significant burden of RSV," said GSK’s chief scientific officer, Tony Wood, PhD, in a company statement. "Our focus now is to ensure eligible older adults in the U.S. can access the vaccine as quickly as possible and to progress regulatory review in other countries."

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

BOSTON – The investigational drug donanemab yielded greater amyloid clearance and amyloid plaque reduction than aducanumab in early, symptomatic Alzheimer’s disease, according to the results of a head-to-head study.

Nearly 40% of patients treated with donanemab had amyloid clearance at 6 months compared with less than 2% of those who received aducanumab, which was approved in 2021 amid a great deal of controversy.

Titration for donanemab progressed more quickly, with participants receiving a maximum dose twice as early as those on aducanumab, without any increase in rates of amyloid-related imaging abnormalities (ARIA) – the most common side effect of amyloid drugs.

Early results from the randomized phase 3 TRAILBLAZER-ALZ 4 trial of donanemab come just 3 months after the Food and Drug Administration denied manufacturer Eli Lilly’s request for accelerated approval for the drug.

“This study shows that the drug with the quicker titration scheme, donanemab, produced more amyloid lowering and did it without having more ARIA,” said lead investigator Stephen P. Salloway, MD, director of the Memory and Aging Program at Butler Hospital in Providence, R.I., and a professor of neurology at Brown University.

The findings were presented at the 2023 annual meeting of the American Academy of Neurology.
 

Multicenter, head-to-head trial

Donanemab received breakthrough therapy designation in 2021. The drug works similarly to aducanumab and lecanemab, which was approved earlier this year. All three bind to different parts of the amyloid molecule and stimulate an immune response to help clear amyloid plaques, although they each have a distinctive binding component.

TRAILBLAZER-ALZ 4 was conducted at 31 sites across the United States, enrolling 140 patients aged 50-85 years with early and symptomatic Alzheimer’s disease. Study participants received donanemab or aducanumab at escalating doses for 18 months.

Donanemab was titrated more quickly, with participants receiving 700 mg via IV infusion once a month for 3 months before reaching the maximum dose of 1,400 mg in the fourth month of the study.

Aducanumab titration was slower, beginning at 1 mg/kg via IV monthly for 2 months, then 3 mg/kg for another 2 months, and 6 mg/kg for 2 more months before reaching the maximum dose of 10 mg/kg in the seventh month.

After 6 months of treatment, PET scan analysis revealed that 37.9% of donanemab-treated patients achieved amyloid clearance compared with just 1.6% of those who received aducanumab (P < .001).

Among patients with intermediate tau levels (n = 27 for donanemab and n = 28 for aducanumab), 38.5% of those who received donanemab achieved amyloid clearance compared with 3.8% of patients in the aducanumab group (P = .008).

Amyloid levels were 65.2% lower in donanemab patients, while levels in those receiving aducanumab were reduced by 17.0% (P < .001). Among those with intermediate tau, amyloid levels decreased with donanemab by 63.9% and 25.4% with aducanumab (P ≤ .001).

Investigators also noted a greater reduction in plasma ptau217 with donanemab.

Adverse events were similar between groups, with 62.0% of the donanemab group and 66.7% of aducanumab-treated participants reporting an adverse event.

There were no serious adverse events due to ARIA with donanemab, but one participant in the aducanumab group had a serious adverse event linked to ARIA.

“Even though the amyloid lowering was greater with donanemab, the rate of ARIA was similar, which suggests that the speed and depth of amyloid removal is not driving ARIA,” Dr. Salloway said.

There are three other Trailblazer trials of donanemab. Unlike in similar trials, participants in all three of these studies who received the trial drug could discontinue treatment once criteria for amyloid clearance were met.

That’s precisely what happened with Trailblazer 2, the study on which Lilly based its request for accelerated approval. Ironically, that trial design also contributed to the FDA’s decision to reject that request.

The FDA required data from at least 100 patients who had received donanemab for a minimum of 1 year. While the trial included more than 100 patients, many patients discontinued treatment early after achieving the targeted amount of amyloid clearance.

“They had success, and they got punished for it, in my opinion,” Dr. Salloway said.

Final data from Trailblazer 2 is due in the next month, and if results are positive, Lilly is expected to file for full approval.
 

Questions remain

“This is an interesting study that suggests donanemab may remove amyloid faster in more people than aducanumab,” said Heather Snyder, PhD, Alzheimer’s Association vice president of medical and scientific relations, who commented on the findings.

Howard Fillit, MD, cofounder and chief science officer at the Alzheimer’s Drug Discovery Foundation, also commented on the findings. He noted that faster amyloid clearance “means less time for requiring sometimes burdensome and expensive infusions.”

Both Dr. Snyder and Dr. Fillit noted that longer-term results are needed, along with studies of whether amyloid clearance offers a protective benefit against Alzheimer’s dementia. More results from Trailblazer 4 will be reported after 12 months and again at 18 months.

“There are obviously still a lot of questions about these drugs and whether reducing amyloid plaque will actually preserve cognitive function or at least slow decline,” Dr. Fillit said.

It will also be important to understand the timing of treatment, including when anti-amyloid therapies should be administered and for how long.

“It will be important to understand how these results translate to patient care and treatment plans, should this drug receive FDA approval,” Dr. Snyder said. “Patients should have the opportunity to make a decision, alongside their physician, on a treatment path that is right for them.”

The study was funded by Eli Lilly. Dr. Salloway has been a consultant for Biogen, EISAI, Lilly, Genentech, Novo Nordisk, Prothena, and others. Dr. Snyder and Dr. Fillit have disclosed no relevant financial relationships.
 

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

BOSTON – The investigational drug donanemab yielded greater amyloid clearance and amyloid plaque reduction than aducanumab in early, symptomatic Alzheimer’s disease, according to the results of a head-to-head study.

Nearly 40% of patients treated with donanemab had amyloid clearance at 6 months compared with less than 2% of those who received aducanumab, which was approved in 2021 amid a great deal of controversy.

Titration for donanemab progressed more quickly, with participants receiving a maximum dose twice as early as those on aducanumab, without any increase in rates of amyloid-related imaging abnormalities (ARIA) – the most common side effect of amyloid drugs.

Early results from the randomized phase 3 TRAILBLAZER-ALZ 4 trial of donanemab come just 3 months after the Food and Drug Administration denied manufacturer Eli Lilly’s request for accelerated approval for the drug.

“This study shows that the drug with the quicker titration scheme, donanemab, produced more amyloid lowering and did it without having more ARIA,” said lead investigator Stephen P. Salloway, MD, director of the Memory and Aging Program at Butler Hospital in Providence, R.I., and a professor of neurology at Brown University.

The findings were presented at the 2023 annual meeting of the American Academy of Neurology.
 

Multicenter, head-to-head trial

Donanemab received breakthrough therapy designation in 2021. The drug works similarly to aducanumab and lecanemab, which was approved earlier this year. All three bind to different parts of the amyloid molecule and stimulate an immune response to help clear amyloid plaques, although they each have a distinctive binding component.

TRAILBLAZER-ALZ 4 was conducted at 31 sites across the United States, enrolling 140 patients aged 50-85 years with early and symptomatic Alzheimer’s disease. Study participants received donanemab or aducanumab at escalating doses for 18 months.

Donanemab was titrated more quickly, with participants receiving 700 mg via IV infusion once a month for 3 months before reaching the maximum dose of 1,400 mg in the fourth month of the study.

Aducanumab titration was slower, beginning at 1 mg/kg via IV monthly for 2 months, then 3 mg/kg for another 2 months, and 6 mg/kg for 2 more months before reaching the maximum dose of 10 mg/kg in the seventh month.

After 6 months of treatment, PET scan analysis revealed that 37.9% of donanemab-treated patients achieved amyloid clearance compared with just 1.6% of those who received aducanumab (P < .001).

Among patients with intermediate tau levels (n = 27 for donanemab and n = 28 for aducanumab), 38.5% of those who received donanemab achieved amyloid clearance compared with 3.8% of patients in the aducanumab group (P = .008).

Amyloid levels were 65.2% lower in donanemab patients, while levels in those receiving aducanumab were reduced by 17.0% (P < .001). Among those with intermediate tau, amyloid levels decreased with donanemab by 63.9% and 25.4% with aducanumab (P ≤ .001).

Investigators also noted a greater reduction in plasma ptau217 with donanemab.

Adverse events were similar between groups, with 62.0% of the donanemab group and 66.7% of aducanumab-treated participants reporting an adverse event.

There were no serious adverse events due to ARIA with donanemab, but one participant in the aducanumab group had a serious adverse event linked to ARIA.

“Even though the amyloid lowering was greater with donanemab, the rate of ARIA was similar, which suggests that the speed and depth of amyloid removal is not driving ARIA,” Dr. Salloway said.

There are three other Trailblazer trials of donanemab. Unlike in similar trials, participants in all three of these studies who received the trial drug could discontinue treatment once criteria for amyloid clearance were met.

That’s precisely what happened with Trailblazer 2, the study on which Lilly based its request for accelerated approval. Ironically, that trial design also contributed to the FDA’s decision to reject that request.

The FDA required data from at least 100 patients who had received donanemab for a minimum of 1 year. While the trial included more than 100 patients, many patients discontinued treatment early after achieving the targeted amount of amyloid clearance.

“They had success, and they got punished for it, in my opinion,” Dr. Salloway said.

Final data from Trailblazer 2 is due in the next month, and if results are positive, Lilly is expected to file for full approval.
 

Questions remain

“This is an interesting study that suggests donanemab may remove amyloid faster in more people than aducanumab,” said Heather Snyder, PhD, Alzheimer’s Association vice president of medical and scientific relations, who commented on the findings.

Howard Fillit, MD, cofounder and chief science officer at the Alzheimer’s Drug Discovery Foundation, also commented on the findings. He noted that faster amyloid clearance “means less time for requiring sometimes burdensome and expensive infusions.”

Both Dr. Snyder and Dr. Fillit noted that longer-term results are needed, along with studies of whether amyloid clearance offers a protective benefit against Alzheimer’s dementia. More results from Trailblazer 4 will be reported after 12 months and again at 18 months.

“There are obviously still a lot of questions about these drugs and whether reducing amyloid plaque will actually preserve cognitive function or at least slow decline,” Dr. Fillit said.

It will also be important to understand the timing of treatment, including when anti-amyloid therapies should be administered and for how long.

“It will be important to understand how these results translate to patient care and treatment plans, should this drug receive FDA approval,” Dr. Snyder said. “Patients should have the opportunity to make a decision, alongside their physician, on a treatment path that is right for them.”

The study was funded by Eli Lilly. Dr. Salloway has been a consultant for Biogen, EISAI, Lilly, Genentech, Novo Nordisk, Prothena, and others. Dr. Snyder and Dr. Fillit have disclosed no relevant financial relationships.
 

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

BOSTON – The investigational drug donanemab yielded greater amyloid clearance and amyloid plaque reduction than aducanumab in early, symptomatic Alzheimer’s disease, according to the results of a head-to-head study.

Nearly 40% of patients treated with donanemab had amyloid clearance at 6 months compared with less than 2% of those who received aducanumab, which was approved in 2021 amid a great deal of controversy.

Titration for donanemab progressed more quickly, with participants receiving a maximum dose twice as early as those on aducanumab, without any increase in rates of amyloid-related imaging abnormalities (ARIA) – the most common side effect of amyloid drugs.

Early results from the randomized phase 3 TRAILBLAZER-ALZ 4 trial of donanemab come just 3 months after the Food and Drug Administration denied manufacturer Eli Lilly’s request for accelerated approval for the drug.

“This study shows that the drug with the quicker titration scheme, donanemab, produced more amyloid lowering and did it without having more ARIA,” said lead investigator Stephen P. Salloway, MD, director of the Memory and Aging Program at Butler Hospital in Providence, R.I., and a professor of neurology at Brown University.

The findings were presented at the 2023 annual meeting of the American Academy of Neurology.
 

Multicenter, head-to-head trial

Donanemab received breakthrough therapy designation in 2021. The drug works similarly to aducanumab and lecanemab, which was approved earlier this year. All three bind to different parts of the amyloid molecule and stimulate an immune response to help clear amyloid plaques, although they each have a distinctive binding component.

TRAILBLAZER-ALZ 4 was conducted at 31 sites across the United States, enrolling 140 patients aged 50-85 years with early and symptomatic Alzheimer’s disease. Study participants received donanemab or aducanumab at escalating doses for 18 months.

Donanemab was titrated more quickly, with participants receiving 700 mg via IV infusion once a month for 3 months before reaching the maximum dose of 1,400 mg in the fourth month of the study.

Aducanumab titration was slower, beginning at 1 mg/kg via IV monthly for 2 months, then 3 mg/kg for another 2 months, and 6 mg/kg for 2 more months before reaching the maximum dose of 10 mg/kg in the seventh month.

After 6 months of treatment, PET scan analysis revealed that 37.9% of donanemab-treated patients achieved amyloid clearance compared with just 1.6% of those who received aducanumab (P < .001).

Among patients with intermediate tau levels (n = 27 for donanemab and n = 28 for aducanumab), 38.5% of those who received donanemab achieved amyloid clearance compared with 3.8% of patients in the aducanumab group (P = .008).

Amyloid levels were 65.2% lower in donanemab patients, while levels in those receiving aducanumab were reduced by 17.0% (P < .001). Among those with intermediate tau, amyloid levels decreased with donanemab by 63.9% and 25.4% with aducanumab (P ≤ .001).

Investigators also noted a greater reduction in plasma ptau217 with donanemab.

Adverse events were similar between groups, with 62.0% of the donanemab group and 66.7% of aducanumab-treated participants reporting an adverse event.

There were no serious adverse events due to ARIA with donanemab, but one participant in the aducanumab group had a serious adverse event linked to ARIA.

“Even though the amyloid lowering was greater with donanemab, the rate of ARIA was similar, which suggests that the speed and depth of amyloid removal is not driving ARIA,” Dr. Salloway said.

There are three other Trailblazer trials of donanemab. Unlike in similar trials, participants in all three of these studies who received the trial drug could discontinue treatment once criteria for amyloid clearance were met.

That’s precisely what happened with Trailblazer 2, the study on which Lilly based its request for accelerated approval. Ironically, that trial design also contributed to the FDA’s decision to reject that request.

The FDA required data from at least 100 patients who had received donanemab for a minimum of 1 year. While the trial included more than 100 patients, many patients discontinued treatment early after achieving the targeted amount of amyloid clearance.

“They had success, and they got punished for it, in my opinion,” Dr. Salloway said.

Final data from Trailblazer 2 is due in the next month, and if results are positive, Lilly is expected to file for full approval.
 

Questions remain

“This is an interesting study that suggests donanemab may remove amyloid faster in more people than aducanumab,” said Heather Snyder, PhD, Alzheimer’s Association vice president of medical and scientific relations, who commented on the findings.

Howard Fillit, MD, cofounder and chief science officer at the Alzheimer’s Drug Discovery Foundation, also commented on the findings. He noted that faster amyloid clearance “means less time for requiring sometimes burdensome and expensive infusions.”

Both Dr. Snyder and Dr. Fillit noted that longer-term results are needed, along with studies of whether amyloid clearance offers a protective benefit against Alzheimer’s dementia. More results from Trailblazer 4 will be reported after 12 months and again at 18 months.

“There are obviously still a lot of questions about these drugs and whether reducing amyloid plaque will actually preserve cognitive function or at least slow decline,” Dr. Fillit said.

It will also be important to understand the timing of treatment, including when anti-amyloid therapies should be administered and for how long.

“It will be important to understand how these results translate to patient care and treatment plans, should this drug receive FDA approval,” Dr. Snyder said. “Patients should have the opportunity to make a decision, alongside their physician, on a treatment path that is right for them.”

The study was funded by Eli Lilly. Dr. Salloway has been a consultant for Biogen, EISAI, Lilly, Genentech, Novo Nordisk, Prothena, and others. Dr. Snyder and Dr. Fillit have disclosed no relevant financial relationships.
 

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

SAN DIEGO – Emerging biomarkers and treatments offer more options to diagnose and manage Alzheimer’s disease (AD) and related dementias, but high costs and potentially serious complications mean using them with caution, said a presenter at the annual meeting of the American College of Physicians.

Dementia prevalence is increasing as the proportion of the U.S. population older than 65 rises, said Zaldy Tan, MD, professor of neurology at Cedars-Sinai Medical Center, Los Angeles. AD deaths more than doubled between 2000 and 2018, he noted, while deaths from HIV infection, stroke, and heart disease decreased.

Most people in the United States who have AD are White, but studies suggest that, compared with Whites, the risk of AD is two times higher in Blacks and 1.5 times higher in Hispanics . “These data suggest that both genes and social determinants of health are at play,” Dr. Tan said.
 

Diagnosis of Alzheimer’s disease

The different types of dementia make it challenging for primary care physicians to identify the cause of cognitive impairment. “Even though AD is the most common type, clinicians should keep in mind that another type of dementia may be the cause of cognitive impairment,” Dr. Tan cautioned. Other dementia diagnoses include vascular, Lewy body, and frontotemporal.

Diagnostic criteria for AD include evidence of significant cognitive decline in at least one cognitive domain that interferes with independence in everyday activities, as well as the absence of another mental disorder or delirium that would explain the cognitive deficits.

“We see many patients with depressive symptoms and mild cognitive impairment, and it is not always easy to tell which of them have dementia because of the overlap in the symptoms of depression and AD,” said internist Roderick Kim, MD, of Grand Rapids, Mich., who attended the session.

It can be challenging to convince patients to undergo the appropriate diagnostic workup, Dr. Kim said. “This can delay treatment, so it is important to explain to patients that cognitive decline can progress quickly and that there are treatment options to slow it down.”
 

Why do we need biomarkers for Alzheimer’s disease?

AD is characterized by a long preclinical phase with no specific symptoms other than the typical signs and symptoms of aging, Dr. Tan said. That means cognitive impairment progresses rapidly after diagnosis in most patients with AD.

“In most cases, an accurate history, physical and neurologic examinations, basic labs, and neuroimaging are sufficient for memory loss evaluation. However, as more disease-modifying therapies come to market, biomarkers will rise in importance in primary care,” he said.

This long asymptomatic phase of AD creates the need for diagnostic biomarkers for an earlier diagnosis, he said. Amyloid-beta and tau deposits in PET images and the levels of amyloid-beta seeds, phosphorylated tau, and neurofilament light chain in the cerebrospinal fluid can be used as diagnostic biomarkers in patients with suspected AD. Emerging blood biomarkers for earlier detection include the levels of amyloid-beta_1–42, phosphorylated tau, and neurofilament light chain.

With biomarkers and other new tools for the diagnosis of dementia in primary care, Dr. Tan said: “The greatest challenge is cost, as blood-based biomarkers are not currently covered by insurance and still rather costly. In addition, blood-based biomarkers will need to receive [Food and Drug Administration] approval in order to have more widespread availability.”


 

New and emerging therapies for Alzheimer’s disease

There are two classes of FDA-approved medications to manage cognitive symptoms of dementia: acetylcholinesterase inhibitors and N-methyl-D-aspartate receptor antagonists. The selections may be trial and error for each patient, Dr. Tan said.

“The approved medications can exert subtle benefits that are clinically observable. Thus, barring any contraindications or intolerance, most patients with AD would benefit from a trial of one or both of these medication classes,” said Dr. Tan. He added that it is equally important to wean off and discontinue these medications if there is intolerance or lack of a subjective or objective beneficial response.

Other medications are available for some of the most common behavioral problems associated with dementia, such as agitation, depression, and disorientation. Dr. Tan advised not to prescribe behavioral medications until nonpharmacologic interventions prove to be ineffective or impractical. Behavioral medications have many side effects, some of which are potentially serious, he said, so the risk-benefit ratio should be considered.

In his own practice, when nonpharmacologic strategies do not improve the behavioral symptoms of dementia, Dr. Tan said that, “in cases where a person is at risk of harm to themselves or others, a discussion with the patient and their caregivers about the pros and cons of medications to treat the behavior need to be had. Careful monitoring of the response and dose escalation or deprescribing when appropriate is important to keep in mind.”

Disease-modifying agents have recently provided new hope for AD treatment. Aducanumab and lecanemab, both monoclonal antibodies that target amyloids, are the first two drugs that received accelerated FDA approval for AD.

Although these monoclonal antibodies can help clear deposited amyloid plaques and show some benefit in slowing cognitive impairment in clinical trials, the real-world benefits were unclear enough for Medicare to limit coverage to people enrolled in approved studies to gather more data. Additionally, these agents can cause potentially amyloid-related imaging abnormalities, which may indicate edema, effusion, or microhemorrhage. Therefore, clinicians need to have a clear conversation of risks and benefits with patients and caregivers about these treatments.
 

Looking ahead

When asked about the most promising emerging technologies or techniques related to dementia diagnosis and management, Dr. Tan noted that multiple technology companies and start-ups are looking for new ways to detect dementia earlier or keep persons with dementia safe at home. Some devices deliver brain waves, computerized brain games or tests, automated pill dispensers, and fall monitors.

“Some of these are potentially helpful, but not every person with dementia will benefit. In addition, most of these technologies are out-of-pocket expenses for the patients and their families. It is important to know what is out there but also be cautious about outrageous claims,” he added.

Dr. Tan reported no relationships with entities whose primary business is producing, marketing, selling, reselling, or distributing health care products used by or on patients.

SAN DIEGO – Emerging biomarkers and treatments offer more options to diagnose and manage Alzheimer’s disease (AD) and related dementias, but high costs and potentially serious complications mean using them with caution, said a presenter at the annual meeting of the American College of Physicians.

Dementia prevalence is increasing as the proportion of the U.S. population older than 65 rises, said Zaldy Tan, MD, professor of neurology at Cedars-Sinai Medical Center, Los Angeles. AD deaths more than doubled between 2000 and 2018, he noted, while deaths from HIV infection, stroke, and heart disease decreased.

Most people in the United States who have AD are White, but studies suggest that, compared with Whites, the risk of AD is two times higher in Blacks and 1.5 times higher in Hispanics . “These data suggest that both genes and social determinants of health are at play,” Dr. Tan said.
 

Diagnosis of Alzheimer’s disease

The different types of dementia make it challenging for primary care physicians to identify the cause of cognitive impairment. “Even though AD is the most common type, clinicians should keep in mind that another type of dementia may be the cause of cognitive impairment,” Dr. Tan cautioned. Other dementia diagnoses include vascular, Lewy body, and frontotemporal.

Diagnostic criteria for AD include evidence of significant cognitive decline in at least one cognitive domain that interferes with independence in everyday activities, as well as the absence of another mental disorder or delirium that would explain the cognitive deficits.

“We see many patients with depressive symptoms and mild cognitive impairment, and it is not always easy to tell which of them have dementia because of the overlap in the symptoms of depression and AD,” said internist Roderick Kim, MD, of Grand Rapids, Mich., who attended the session.

It can be challenging to convince patients to undergo the appropriate diagnostic workup, Dr. Kim said. “This can delay treatment, so it is important to explain to patients that cognitive decline can progress quickly and that there are treatment options to slow it down.”
 

Why do we need biomarkers for Alzheimer’s disease?

AD is characterized by a long preclinical phase with no specific symptoms other than the typical signs and symptoms of aging, Dr. Tan said. That means cognitive impairment progresses rapidly after diagnosis in most patients with AD.

“In most cases, an accurate history, physical and neurologic examinations, basic labs, and neuroimaging are sufficient for memory loss evaluation. However, as more disease-modifying therapies come to market, biomarkers will rise in importance in primary care,” he said.

This long asymptomatic phase of AD creates the need for diagnostic biomarkers for an earlier diagnosis, he said. Amyloid-beta and tau deposits in PET images and the levels of amyloid-beta seeds, phosphorylated tau, and neurofilament light chain in the cerebrospinal fluid can be used as diagnostic biomarkers in patients with suspected AD. Emerging blood biomarkers for earlier detection include the levels of amyloid-beta_1–42, phosphorylated tau, and neurofilament light chain.

With biomarkers and other new tools for the diagnosis of dementia in primary care, Dr. Tan said: “The greatest challenge is cost, as blood-based biomarkers are not currently covered by insurance and still rather costly. In addition, blood-based biomarkers will need to receive [Food and Drug Administration] approval in order to have more widespread availability.”


 

New and emerging therapies for Alzheimer’s disease

There are two classes of FDA-approved medications to manage cognitive symptoms of dementia: acetylcholinesterase inhibitors and N-methyl-D-aspartate receptor antagonists. The selections may be trial and error for each patient, Dr. Tan said.

“The approved medications can exert subtle benefits that are clinically observable. Thus, barring any contraindications or intolerance, most patients with AD would benefit from a trial of one or both of these medication classes,” said Dr. Tan. He added that it is equally important to wean off and discontinue these medications if there is intolerance or lack of a subjective or objective beneficial response.

Other medications are available for some of the most common behavioral problems associated with dementia, such as agitation, depression, and disorientation. Dr. Tan advised not to prescribe behavioral medications until nonpharmacologic interventions prove to be ineffective or impractical. Behavioral medications have many side effects, some of which are potentially serious, he said, so the risk-benefit ratio should be considered.

In his own practice, when nonpharmacologic strategies do not improve the behavioral symptoms of dementia, Dr. Tan said that, “in cases where a person is at risk of harm to themselves or others, a discussion with the patient and their caregivers about the pros and cons of medications to treat the behavior need to be had. Careful monitoring of the response and dose escalation or deprescribing when appropriate is important to keep in mind.”

Disease-modifying agents have recently provided new hope for AD treatment. Aducanumab and lecanemab, both monoclonal antibodies that target amyloids, are the first two drugs that received accelerated FDA approval for AD.

Although these monoclonal antibodies can help clear deposited amyloid plaques and show some benefit in slowing cognitive impairment in clinical trials, the real-world benefits were unclear enough for Medicare to limit coverage to people enrolled in approved studies to gather more data. Additionally, these agents can cause potentially amyloid-related imaging abnormalities, which may indicate edema, effusion, or microhemorrhage. Therefore, clinicians need to have a clear conversation of risks and benefits with patients and caregivers about these treatments.
 

Looking ahead

When asked about the most promising emerging technologies or techniques related to dementia diagnosis and management, Dr. Tan noted that multiple technology companies and start-ups are looking for new ways to detect dementia earlier or keep persons with dementia safe at home. Some devices deliver brain waves, computerized brain games or tests, automated pill dispensers, and fall monitors.

“Some of these are potentially helpful, but not every person with dementia will benefit. In addition, most of these technologies are out-of-pocket expenses for the patients and their families. It is important to know what is out there but also be cautious about outrageous claims,” he added.

Dr. Tan reported no relationships with entities whose primary business is producing, marketing, selling, reselling, or distributing health care products used by or on patients.

SAN DIEGO – Emerging biomarkers and treatments offer more options to diagnose and manage Alzheimer’s disease (AD) and related dementias, but high costs and potentially serious complications mean using them with caution, said a presenter at the annual meeting of the American College of Physicians.

Dementia prevalence is increasing as the proportion of the U.S. population older than 65 rises, said Zaldy Tan, MD, professor of neurology at Cedars-Sinai Medical Center, Los Angeles. AD deaths more than doubled between 2000 and 2018, he noted, while deaths from HIV infection, stroke, and heart disease decreased.

Most people in the United States who have AD are White, but studies suggest that, compared with Whites, the risk of AD is two times higher in Blacks and 1.5 times higher in Hispanics . “These data suggest that both genes and social determinants of health are at play,” Dr. Tan said.
 

Diagnosis of Alzheimer’s disease

The different types of dementia make it challenging for primary care physicians to identify the cause of cognitive impairment. “Even though AD is the most common type, clinicians should keep in mind that another type of dementia may be the cause of cognitive impairment,” Dr. Tan cautioned. Other dementia diagnoses include vascular, Lewy body, and frontotemporal.

Diagnostic criteria for AD include evidence of significant cognitive decline in at least one cognitive domain that interferes with independence in everyday activities, as well as the absence of another mental disorder or delirium that would explain the cognitive deficits.

“We see many patients with depressive symptoms and mild cognitive impairment, and it is not always easy to tell which of them have dementia because of the overlap in the symptoms of depression and AD,” said internist Roderick Kim, MD, of Grand Rapids, Mich., who attended the session.

It can be challenging to convince patients to undergo the appropriate diagnostic workup, Dr. Kim said. “This can delay treatment, so it is important to explain to patients that cognitive decline can progress quickly and that there are treatment options to slow it down.”
 

Why do we need biomarkers for Alzheimer’s disease?

AD is characterized by a long preclinical phase with no specific symptoms other than the typical signs and symptoms of aging, Dr. Tan said. That means cognitive impairment progresses rapidly after diagnosis in most patients with AD.

“In most cases, an accurate history, physical and neurologic examinations, basic labs, and neuroimaging are sufficient for memory loss evaluation. However, as more disease-modifying therapies come to market, biomarkers will rise in importance in primary care,” he said.

This long asymptomatic phase of AD creates the need for diagnostic biomarkers for an earlier diagnosis, he said. Amyloid-beta and tau deposits in PET images and the levels of amyloid-beta seeds, phosphorylated tau, and neurofilament light chain in the cerebrospinal fluid can be used as diagnostic biomarkers in patients with suspected AD. Emerging blood biomarkers for earlier detection include the levels of amyloid-beta_1–42, phosphorylated tau, and neurofilament light chain.

With biomarkers and other new tools for the diagnosis of dementia in primary care, Dr. Tan said: “The greatest challenge is cost, as blood-based biomarkers are not currently covered by insurance and still rather costly. In addition, blood-based biomarkers will need to receive [Food and Drug Administration] approval in order to have more widespread availability.”


 

New and emerging therapies for Alzheimer’s disease

There are two classes of FDA-approved medications to manage cognitive symptoms of dementia: acetylcholinesterase inhibitors and N-methyl-D-aspartate receptor antagonists. The selections may be trial and error for each patient, Dr. Tan said.

“The approved medications can exert subtle benefits that are clinically observable. Thus, barring any contraindications or intolerance, most patients with AD would benefit from a trial of one or both of these medication classes,” said Dr. Tan. He added that it is equally important to wean off and discontinue these medications if there is intolerance or lack of a subjective or objective beneficial response.

Other medications are available for some of the most common behavioral problems associated with dementia, such as agitation, depression, and disorientation. Dr. Tan advised not to prescribe behavioral medications until nonpharmacologic interventions prove to be ineffective or impractical. Behavioral medications have many side effects, some of which are potentially serious, he said, so the risk-benefit ratio should be considered.

In his own practice, when nonpharmacologic strategies do not improve the behavioral symptoms of dementia, Dr. Tan said that, “in cases where a person is at risk of harm to themselves or others, a discussion with the patient and their caregivers about the pros and cons of medications to treat the behavior need to be had. Careful monitoring of the response and dose escalation or deprescribing when appropriate is important to keep in mind.”

Disease-modifying agents have recently provided new hope for AD treatment. Aducanumab and lecanemab, both monoclonal antibodies that target amyloids, are the first two drugs that received accelerated FDA approval for AD.

Although these monoclonal antibodies can help clear deposited amyloid plaques and show some benefit in slowing cognitive impairment in clinical trials, the real-world benefits were unclear enough for Medicare to limit coverage to people enrolled in approved studies to gather more data. Additionally, these agents can cause potentially amyloid-related imaging abnormalities, which may indicate edema, effusion, or microhemorrhage. Therefore, clinicians need to have a clear conversation of risks and benefits with patients and caregivers about these treatments.
 

Looking ahead

When asked about the most promising emerging technologies or techniques related to dementia diagnosis and management, Dr. Tan noted that multiple technology companies and start-ups are looking for new ways to detect dementia earlier or keep persons with dementia safe at home. Some devices deliver brain waves, computerized brain games or tests, automated pill dispensers, and fall monitors.

“Some of these are potentially helpful, but not every person with dementia will benefit. In addition, most of these technologies are out-of-pocket expenses for the patients and their families. It is important to know what is out there but also be cautious about outrageous claims,” he added.

Dr. Tan reported no relationships with entities whose primary business is producing, marketing, selling, reselling, or distributing health care products used by or on patients.

In the United States, type 2 diabetes (T2D) more commonly affects people older than 40 years, but it is most prevalent among adults over age 65, affecting more than 29% of this population. The heterogeneity in the health and functional status of older adults presents a challenge in the management and treatment of older patients with T2D. Moreover, there is an increased risk for health-related comorbidities and complications from diabetes treatment (for example, hypoglycemia) in older adults. Physiologic changes, such as decreased renal function, cognitive decline, and sarcopenia, may lead to an increased risk for adverse reactions to medications and require an individualized treatment approach. Although there have been a limited number of randomized controlled studies targeting older adults with multiple comorbidities and poor health status, subanalyses of diabetes trials with a subpopulation of older adults have provided additional evidence to better guide therapeutic approaches in caring for older patients with T2D.

Here’s a guide to developing personalized therapeutic regimens for older patients with T2D using lifestyle interventions, pharmacotherapy, and diabetes technology.
 

Determining an optimal glycemic target

An important first step in diabetes treatment is to determine the optimal glycemic target for patients. Although data support intensive glycemic control (hemoglobin A1c < 7%) to prevent complications from diabetes in younger patients with recently diagnosed disease, the data are less compelling in trials involving older populations with longer durations of T2D. One observational study with 71,092 older adults over age 60 reported a U-shaped correlation between A1c and mortality, with higher risks for mortality in those with A1c levels < 6% and ≥ 11%, compared with those with A1c levels of 6%-9%. Risks for any diabetes complications were higher at an A1c level ≥ 8%. Another observational study reported a U-shaped association between A1c and mortality, with the lowest hazard ratio for mortality at an A1c level of about 7.5%. Similarly, the ACCORD trial, which included older and middle-aged patients with T2D who had or were at risk for atherosclerotic cardiovascular disease, found that mortality followed a U-shaped curve at the low (A1c < 7%) and high (A1c > 8%) ends in patients who were given standard glycemic therapy. Hence, there has been a general trend to recommend less strict glycemic control in older adults.

However, it is important to remember that older patients with T2D are a heterogeneous group. The spectrum includes adults with recent-onset diabetes with no or few complications, those with long-standing diabetes and many complications, and frail older adults with multiple comorbidities and complications. Determining the optimal glycemic target for an older patient with T2D requires assessment not only of the patient’s medical status and comorbidities but also functional status, cognitive and psychological health, social situation, individual preferences, and life expectancy. The American Diabetes Association Standards of Medical Care in Diabetes provides the following guidance in determining the optimal glycemic control for older adults:

• Healthy adults with few coexisting chronic illnesses and intact cognitive and functional status should have an A1c level < 7.0%-7.5%.
• Adults with complex or intermediate comorbidities (multiple coexisting chronic illnesses, or two or more instrumental activities of daily living impairments, or mild to moderate cognitive impairment) should have an A1c level < 8.0%.
• Patients with poor health (long-term care or end-stage chronic illnesses or moderate to severe cognitive impairment or two or more activities of daily living impairments) should avoid reliance on A1c, and the goal is to avoid hypoglycemia and symptomatic hyperglycemia.

Because older patients are at a higher risk for complications and adverse effects from polypharmacy, regular assessments are recommended and treatment plans should be routinely reviewed and modified to avoid overtreatment.
 

Lifestyle interventions and pharmacotherapy

Lifestyle interventions, such as exercise, optimal nutrition, and protein intake, are integral in treating older patients with T2D. Older adults should engage in regular exercise (that is, aerobic activity, weight-bearing exercise, or resistance training), and the activity should be customized to frailty status. Regular exercise improves insulin sensitivity and glucose control, enhances functional status, and provides cardiometabolic benefits. Optimal nutrition and adequate protein intake are also important to prevent the development or worsening of sarcopenia and frailty.

Several factors must be considered when choosing pharmacotherapy for T2D treatment in older adults. These patients are at higher risk for adverse reactions to medications that can trigger hypoglycemia and serious cardiovascular events, and worsen cognitive function. Therefore, side effects should always be reviewed when choosing antidiabetic drugs. The complexity of treatment plans needs to be matched with the patients’ self-management abilities and available social support. Medication costs and insurance coverage should be considered because many older adults live on a fixed income. Although limited, data exist on the safety and efficacy of some glucose-lowering agents in older adults, which can provide guidance for choosing the optimal therapy for these patients.

Among the insulin sensitizers, metformin is most commonly used because of its efficacy, low risk for hypoglycemia, and affordability. Metformin can be safely used in the setting of reduced renal function down to the estimated glomerular filtration rate ≥ 30 mL/min per 1.73 m². However, metformin should be avoided in patients with more advanced renal disease, liver failure, or heart failure. In older patients with T2D, potential concerns of metformin include gastrointestinal side effects, leading to reduced appetite, mild weight loss, and risk for vitamin B12 deficiency.

Pioglitazone, an oral antidiabetic in the thiazolidinedione (TZD) class, also targets insulin resistance and may provide some cardiovascular benefits. However, these agents are not commonly used in treating older patients with T2D owing to associated risk for edema, heart failure, osteoporosis/fractures, and bladder cancer.

Sulfonylureas and meglitinides are insulin secretagogues, which can promote insulin release independent of glucose levels. Sulfonylureas are typically avoided in older patients because they are associated with high risk for hypoglycemia. Meglitinides have a lower hypoglycemia risk than sulfonylureas because of their short duration of action; however, they are more expensive and require multiple daily administration, which can lead to issues with adherence.

Since 2008, there have been numerous cardiovascular outcomes trials assessing the safety and efficacy of T2D therapies that included a subpopulation of older patients either with cardiovascular disease or at high risk for cardiovascular disease. Post hoc analysis of data from these trials and smaller studies dedicated to older adults demonstrated the safety and efficacy of most incretin-based therapies and sodium-glucose cotransporter 2 (SGLT2) inhibitors in these patients. These newer medications have low hypoglycemia risk if not used in combination with insulin or insulin secretagogues.

Dipeptidyl peptidase 4 (DPP-4) inhibitors have the mildest side effect profile. However, they can be expensive and not reduce major adverse cardiovascular outcomes, and one agent, saxagliptin, has been associated with increased risk for heart failure hospitalization. Some glucagon-like peptide 1 (GLP-1) receptor agonists are effective in reducing major adverse cardiovascular events (cardiovascular deaths, stroke, and myocardial infarction) in patients older and younger than age 65. However, the gastrointestinal side effects and weight loss associated with this medication can be problematic for older patients. Most of the GLP-1 receptor agonists are injectables, which require good visual, motor, and cognitive skills for administration. SGLT2 inhibitors offer benefits for patients with T2D who have established cardiovascular disease, heart failure, and chronic kidney disease, with possible greater cardiovascular benefits in older adults. Adverse effects associated with SGLT2 inhibitors, such as weight loss, volume depletion, urinary incontinence, and genitourinary infections, may be a concern in older patients with T2D who are using these medications.

Because the insulin-secreting capacity of the pancreas declines with age, insulin therapy may be required for treatment of T2D in older patients. Insulin therapy can be complex and consideration must be given to patients’ social circumstances, as well as their physical and cognitive abilities. Older adults may need adaptive strategies, such as additional lighting, magnification glass, and premixed syringes. Simplification of complex insulin therapy (discontinuation of prandial insulin or sliding scale, changing timing of basal insulin) and use of insulin analogs with lower hypoglycemia risks should be considered. Weight gain as a result of insulin therapy may be beneficial in older adults with sarcopenia or frailty.
 

T2D technology for glycemic improvement

There have been major technological advancements in diabetes therapy. Continuous glucose monitors (CGMs) and automated insulin delivery systems can improve glycemic control, decrease the rate of hypoglycemia, and enhance the quality of life of older patients. Most of the studies evaluating the use of automated insulin delivery systems in older patients have focused on those with type 1 diabetes and demonstrated improvement in glycemic control and/or reduced hypoglycemia. The DIAMOND trial demonstrated improved A1c and reduced glycemic variability with the use of CGM in adults older than 60 years with either type 1 or type 2 diabetes on multiple daily injections. Bluetooth-enabled “smart” insulin pens, which record the time and dose of insulin administrations, can also be a great asset in caring for older patients, especially those with cognitive impairment. With better insurance coverage, diabetes technologies may become more accessible and an asset in treating older patients with T2D.

In conclusion, management of T2D in older adults requires an individualized approach because of the heterogeneity in their health and functional status. Because cardiovascular disease is the leading cause of mortality in older patients with T2D, treatment plans should also address frequently coexisting cardiovascular risk factors, such as hypertension and hyperlipidemia. Clinicians should consider patients’ overall health, comorbidities, cognitive and functional status, social support systems, preferences, and life expectancy when developing individualized therapeutic plans.

Dr. Gunawan is an assistant professor in the department of internal medicine at UT Southwestern Medical Center, Dallas. She reported no relevant conflicts of interest.

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

In the United States, type 2 diabetes (T2D) more commonly affects people older than 40 years, but it is most prevalent among adults over age 65, affecting more than 29% of this population. The heterogeneity in the health and functional status of older adults presents a challenge in the management and treatment of older patients with T2D. Moreover, there is an increased risk for health-related comorbidities and complications from diabetes treatment (for example, hypoglycemia) in older adults. Physiologic changes, such as decreased renal function, cognitive decline, and sarcopenia, may lead to an increased risk for adverse reactions to medications and require an individualized treatment approach. Although there have been a limited number of randomized controlled studies targeting older adults with multiple comorbidities and poor health status, subanalyses of diabetes trials with a subpopulation of older adults have provided additional evidence to better guide therapeutic approaches in caring for older patients with T2D.

Here’s a guide to developing personalized therapeutic regimens for older patients with T2D using lifestyle interventions, pharmacotherapy, and diabetes technology.
 

Determining an optimal glycemic target

An important first step in diabetes treatment is to determine the optimal glycemic target for patients. Although data support intensive glycemic control (hemoglobin A1c < 7%) to prevent complications from diabetes in younger patients with recently diagnosed disease, the data are less compelling in trials involving older populations with longer durations of T2D. One observational study with 71,092 older adults over age 60 reported a U-shaped correlation between A1c and mortality, with higher risks for mortality in those with A1c levels < 6% and ≥ 11%, compared with those with A1c levels of 6%-9%. Risks for any diabetes complications were higher at an A1c level ≥ 8%. Another observational study reported a U-shaped association between A1c and mortality, with the lowest hazard ratio for mortality at an A1c level of about 7.5%. Similarly, the ACCORD trial, which included older and middle-aged patients with T2D who had or were at risk for atherosclerotic cardiovascular disease, found that mortality followed a U-shaped curve at the low (A1c < 7%) and high (A1c > 8%) ends in patients who were given standard glycemic therapy. Hence, there has been a general trend to recommend less strict glycemic control in older adults.

However, it is important to remember that older patients with T2D are a heterogeneous group. The spectrum includes adults with recent-onset diabetes with no or few complications, those with long-standing diabetes and many complications, and frail older adults with multiple comorbidities and complications. Determining the optimal glycemic target for an older patient with T2D requires assessment not only of the patient’s medical status and comorbidities but also functional status, cognitive and psychological health, social situation, individual preferences, and life expectancy. The American Diabetes Association Standards of Medical Care in Diabetes provides the following guidance in determining the optimal glycemic control for older adults:

• Healthy adults with few coexisting chronic illnesses and intact cognitive and functional status should have an A1c level < 7.0%-7.5%.
• Adults with complex or intermediate comorbidities (multiple coexisting chronic illnesses, or two or more instrumental activities of daily living impairments, or mild to moderate cognitive impairment) should have an A1c level < 8.0%.
• Patients with poor health (long-term care or end-stage chronic illnesses or moderate to severe cognitive impairment or two or more activities of daily living impairments) should avoid reliance on A1c, and the goal is to avoid hypoglycemia and symptomatic hyperglycemia.

Because older patients are at a higher risk for complications and adverse effects from polypharmacy, regular assessments are recommended and treatment plans should be routinely reviewed and modified to avoid overtreatment.
 

Lifestyle interventions and pharmacotherapy

Lifestyle interventions, such as exercise, optimal nutrition, and protein intake, are integral in treating older patients with T2D. Older adults should engage in regular exercise (that is, aerobic activity, weight-bearing exercise, or resistance training), and the activity should be customized to frailty status. Regular exercise improves insulin sensitivity and glucose control, enhances functional status, and provides cardiometabolic benefits. Optimal nutrition and adequate protein intake are also important to prevent the development or worsening of sarcopenia and frailty.

Several factors must be considered when choosing pharmacotherapy for T2D treatment in older adults. These patients are at higher risk for adverse reactions to medications that can trigger hypoglycemia and serious cardiovascular events, and worsen cognitive function. Therefore, side effects should always be reviewed when choosing antidiabetic drugs. The complexity of treatment plans needs to be matched with the patients’ self-management abilities and available social support. Medication costs and insurance coverage should be considered because many older adults live on a fixed income. Although limited, data exist on the safety and efficacy of some glucose-lowering agents in older adults, which can provide guidance for choosing the optimal therapy for these patients.

Among the insulin sensitizers, metformin is most commonly used because of its efficacy, low risk for hypoglycemia, and affordability. Metformin can be safely used in the setting of reduced renal function down to the estimated glomerular filtration rate ≥ 30 mL/min per 1.73 m². However, metformin should be avoided in patients with more advanced renal disease, liver failure, or heart failure. In older patients with T2D, potential concerns of metformin include gastrointestinal side effects, leading to reduced appetite, mild weight loss, and risk for vitamin B12 deficiency.

Pioglitazone, an oral antidiabetic in the thiazolidinedione (TZD) class, also targets insulin resistance and may provide some cardiovascular benefits. However, these agents are not commonly used in treating older patients with T2D owing to associated risk for edema, heart failure, osteoporosis/fractures, and bladder cancer.

Sulfonylureas and meglitinides are insulin secretagogues, which can promote insulin release independent of glucose levels. Sulfonylureas are typically avoided in older patients because they are associated with high risk for hypoglycemia. Meglitinides have a lower hypoglycemia risk than sulfonylureas because of their short duration of action; however, they are more expensive and require multiple daily administration, which can lead to issues with adherence.

Since 2008, there have been numerous cardiovascular outcomes trials assessing the safety and efficacy of T2D therapies that included a subpopulation of older patients either with cardiovascular disease or at high risk for cardiovascular disease. Post hoc analysis of data from these trials and smaller studies dedicated to older adults demonstrated the safety and efficacy of most incretin-based therapies and sodium-glucose cotransporter 2 (SGLT2) inhibitors in these patients. These newer medications have low hypoglycemia risk if not used in combination with insulin or insulin secretagogues.

Dipeptidyl peptidase 4 (DPP-4) inhibitors have the mildest side effect profile. However, they can be expensive and not reduce major adverse cardiovascular outcomes, and one agent, saxagliptin, has been associated with increased risk for heart failure hospitalization. Some glucagon-like peptide 1 (GLP-1) receptor agonists are effective in reducing major adverse cardiovascular events (cardiovascular deaths, stroke, and myocardial infarction) in patients older and younger than age 65. However, the gastrointestinal side effects and weight loss associated with this medication can be problematic for older patients. Most of the GLP-1 receptor agonists are injectables, which require good visual, motor, and cognitive skills for administration. SGLT2 inhibitors offer benefits for patients with T2D who have established cardiovascular disease, heart failure, and chronic kidney disease, with possible greater cardiovascular benefits in older adults. Adverse effects associated with SGLT2 inhibitors, such as weight loss, volume depletion, urinary incontinence, and genitourinary infections, may be a concern in older patients with T2D who are using these medications.

Because the insulin-secreting capacity of the pancreas declines with age, insulin therapy may be required for treatment of T2D in older patients. Insulin therapy can be complex and consideration must be given to patients’ social circumstances, as well as their physical and cognitive abilities. Older adults may need adaptive strategies, such as additional lighting, magnification glass, and premixed syringes. Simplification of complex insulin therapy (discontinuation of prandial insulin or sliding scale, changing timing of basal insulin) and use of insulin analogs with lower hypoglycemia risks should be considered. Weight gain as a result of insulin therapy may be beneficial in older adults with sarcopenia or frailty.
 

T2D technology for glycemic improvement

There have been major technological advancements in diabetes therapy. Continuous glucose monitors (CGMs) and automated insulin delivery systems can improve glycemic control, decrease the rate of hypoglycemia, and enhance the quality of life of older patients. Most of the studies evaluating the use of automated insulin delivery systems in older patients have focused on those with type 1 diabetes and demonstrated improvement in glycemic control and/or reduced hypoglycemia. The DIAMOND trial demonstrated improved A1c and reduced glycemic variability with the use of CGM in adults older than 60 years with either type 1 or type 2 diabetes on multiple daily injections. Bluetooth-enabled “smart” insulin pens, which record the time and dose of insulin administrations, can also be a great asset in caring for older patients, especially those with cognitive impairment. With better insurance coverage, diabetes technologies may become more accessible and an asset in treating older patients with T2D.

In conclusion, management of T2D in older adults requires an individualized approach because of the heterogeneity in their health and functional status. Because cardiovascular disease is the leading cause of mortality in older patients with T2D, treatment plans should also address frequently coexisting cardiovascular risk factors, such as hypertension and hyperlipidemia. Clinicians should consider patients’ overall health, comorbidities, cognitive and functional status, social support systems, preferences, and life expectancy when developing individualized therapeutic plans.

Dr. Gunawan is an assistant professor in the department of internal medicine at UT Southwestern Medical Center, Dallas. She reported no relevant conflicts of interest.

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

In the United States, type 2 diabetes (T2D) more commonly affects people older than 40 years, but it is most prevalent among adults over age 65, affecting more than 29% of this population. The heterogeneity in the health and functional status of older adults presents a challenge in the management and treatment of older patients with T2D. Moreover, there is an increased risk for health-related comorbidities and complications from diabetes treatment (for example, hypoglycemia) in older adults. Physiologic changes, such as decreased renal function, cognitive decline, and sarcopenia, may lead to an increased risk for adverse reactions to medications and require an individualized treatment approach. Although there have been a limited number of randomized controlled studies targeting older adults with multiple comorbidities and poor health status, subanalyses of diabetes trials with a subpopulation of older adults have provided additional evidence to better guide therapeutic approaches in caring for older patients with T2D.

Here’s a guide to developing personalized therapeutic regimens for older patients with T2D using lifestyle interventions, pharmacotherapy, and diabetes technology.
 

Determining an optimal glycemic target

An important first step in diabetes treatment is to determine the optimal glycemic target for patients. Although data support intensive glycemic control (hemoglobin A1c < 7%) to prevent complications from diabetes in younger patients with recently diagnosed disease, the data are less compelling in trials involving older populations with longer durations of T2D. One observational study with 71,092 older adults over age 60 reported a U-shaped correlation between A1c and mortality, with higher risks for mortality in those with A1c levels < 6% and ≥ 11%, compared with those with A1c levels of 6%-9%. Risks for any diabetes complications were higher at an A1c level ≥ 8%. Another observational study reported a U-shaped association between A1c and mortality, with the lowest hazard ratio for mortality at an A1c level of about 7.5%. Similarly, the ACCORD trial, which included older and middle-aged patients with T2D who had or were at risk for atherosclerotic cardiovascular disease, found that mortality followed a U-shaped curve at the low (A1c < 7%) and high (A1c > 8%) ends in patients who were given standard glycemic therapy. Hence, there has been a general trend to recommend less strict glycemic control in older adults.

However, it is important to remember that older patients with T2D are a heterogeneous group. The spectrum includes adults with recent-onset diabetes with no or few complications, those with long-standing diabetes and many complications, and frail older adults with multiple comorbidities and complications. Determining the optimal glycemic target for an older patient with T2D requires assessment not only of the patient’s medical status and comorbidities but also functional status, cognitive and psychological health, social situation, individual preferences, and life expectancy. The American Diabetes Association Standards of Medical Care in Diabetes provides the following guidance in determining the optimal glycemic control for older adults:

• Healthy adults with few coexisting chronic illnesses and intact cognitive and functional status should have an A1c level < 7.0%-7.5%.
• Adults with complex or intermediate comorbidities (multiple coexisting chronic illnesses, or two or more instrumental activities of daily living impairments, or mild to moderate cognitive impairment) should have an A1c level < 8.0%.
• Patients with poor health (long-term care or end-stage chronic illnesses or moderate to severe cognitive impairment or two or more activities of daily living impairments) should avoid reliance on A1c, and the goal is to avoid hypoglycemia and symptomatic hyperglycemia.

Because older patients are at a higher risk for complications and adverse effects from polypharmacy, regular assessments are recommended and treatment plans should be routinely reviewed and modified to avoid overtreatment.
 

Lifestyle interventions and pharmacotherapy

Lifestyle interventions, such as exercise, optimal nutrition, and protein intake, are integral in treating older patients with T2D. Older adults should engage in regular exercise (that is, aerobic activity, weight-bearing exercise, or resistance training), and the activity should be customized to frailty status. Regular exercise improves insulin sensitivity and glucose control, enhances functional status, and provides cardiometabolic benefits. Optimal nutrition and adequate protein intake are also important to prevent the development or worsening of sarcopenia and frailty.

Several factors must be considered when choosing pharmacotherapy for T2D treatment in older adults. These patients are at higher risk for adverse reactions to medications that can trigger hypoglycemia and serious cardiovascular events, and worsen cognitive function. Therefore, side effects should always be reviewed when choosing antidiabetic drugs. The complexity of treatment plans needs to be matched with the patients’ self-management abilities and available social support. Medication costs and insurance coverage should be considered because many older adults live on a fixed income. Although limited, data exist on the safety and efficacy of some glucose-lowering agents in older adults, which can provide guidance for choosing the optimal therapy for these patients.

Among the insulin sensitizers, metformin is most commonly used because of its efficacy, low risk for hypoglycemia, and affordability. Metformin can be safely used in the setting of reduced renal function down to the estimated glomerular filtration rate ≥ 30 mL/min per 1.73 m². However, metformin should be avoided in patients with more advanced renal disease, liver failure, or heart failure. In older patients with T2D, potential concerns of metformin include gastrointestinal side effects, leading to reduced appetite, mild weight loss, and risk for vitamin B12 deficiency.

Pioglitazone, an oral antidiabetic in the thiazolidinedione (TZD) class, also targets insulin resistance and may provide some cardiovascular benefits. However, these agents are not commonly used in treating older patients with T2D owing to associated risk for edema, heart failure, osteoporosis/fractures, and bladder cancer.

Sulfonylureas and meglitinides are insulin secretagogues, which can promote insulin release independent of glucose levels. Sulfonylureas are typically avoided in older patients because they are associated with high risk for hypoglycemia. Meglitinides have a lower hypoglycemia risk than sulfonylureas because of their short duration of action; however, they are more expensive and require multiple daily administration, which can lead to issues with adherence.

Since 2008, there have been numerous cardiovascular outcomes trials assessing the safety and efficacy of T2D therapies that included a subpopulation of older patients either with cardiovascular disease or at high risk for cardiovascular disease. Post hoc analysis of data from these trials and smaller studies dedicated to older adults demonstrated the safety and efficacy of most incretin-based therapies and sodium-glucose cotransporter 2 (SGLT2) inhibitors in these patients. These newer medications have low hypoglycemia risk if not used in combination with insulin or insulin secretagogues.

Dipeptidyl peptidase 4 (DPP-4) inhibitors have the mildest side effect profile. However, they can be expensive and not reduce major adverse cardiovascular outcomes, and one agent, saxagliptin, has been associated with increased risk for heart failure hospitalization. Some glucagon-like peptide 1 (GLP-1) receptor agonists are effective in reducing major adverse cardiovascular events (cardiovascular deaths, stroke, and myocardial infarction) in patients older and younger than age 65. However, the gastrointestinal side effects and weight loss associated with this medication can be problematic for older patients. Most of the GLP-1 receptor agonists are injectables, which require good visual, motor, and cognitive skills for administration. SGLT2 inhibitors offer benefits for patients with T2D who have established cardiovascular disease, heart failure, and chronic kidney disease, with possible greater cardiovascular benefits in older adults. Adverse effects associated with SGLT2 inhibitors, such as weight loss, volume depletion, urinary incontinence, and genitourinary infections, may be a concern in older patients with T2D who are using these medications.

Because the insulin-secreting capacity of the pancreas declines with age, insulin therapy may be required for treatment of T2D in older patients. Insulin therapy can be complex and consideration must be given to patients’ social circumstances, as well as their physical and cognitive abilities. Older adults may need adaptive strategies, such as additional lighting, magnification glass, and premixed syringes. Simplification of complex insulin therapy (discontinuation of prandial insulin or sliding scale, changing timing of basal insulin) and use of insulin analogs with lower hypoglycemia risks should be considered. Weight gain as a result of insulin therapy may be beneficial in older adults with sarcopenia or frailty.
 

T2D technology for glycemic improvement

There have been major technological advancements in diabetes therapy. Continuous glucose monitors (CGMs) and automated insulin delivery systems can improve glycemic control, decrease the rate of hypoglycemia, and enhance the quality of life of older patients. Most of the studies evaluating the use of automated insulin delivery systems in older patients have focused on those with type 1 diabetes and demonstrated improvement in glycemic control and/or reduced hypoglycemia. The DIAMOND trial demonstrated improved A1c and reduced glycemic variability with the use of CGM in adults older than 60 years with either type 1 or type 2 diabetes on multiple daily injections. Bluetooth-enabled “smart” insulin pens, which record the time and dose of insulin administrations, can also be a great asset in caring for older patients, especially those with cognitive impairment. With better insurance coverage, diabetes technologies may become more accessible and an asset in treating older patients with T2D.

In conclusion, management of T2D in older adults requires an individualized approach because of the heterogeneity in their health and functional status. Because cardiovascular disease is the leading cause of mortality in older patients with T2D, treatment plans should also address frequently coexisting cardiovascular risk factors, such as hypertension and hyperlipidemia. Clinicians should consider patients’ overall health, comorbidities, cognitive and functional status, social support systems, preferences, and life expectancy when developing individualized therapeutic plans.

Dr. Gunawan is an assistant professor in the department of internal medicine at UT Southwestern Medical Center, Dallas. She reported no relevant conflicts of interest.

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