Guidelines

Questions about how to prescribe statins for primary prevention abound more than 3 decades after the drugs swept into clinical practice to become a first-line medical approach to cutting cardiovascular (CV) risk. Statin usage recommendations from different bodies can vary in ways both limited and fundamental, spurring the kind of debate that accompanies such a document newly issued by the United States Preventive Services Task Force.

The document, little changed from the draft guidance released for public comment in February, was published online Aug. 23 in JAMA and the USPSTF website. It replaces a similar document issued by the task force in 2016.

The guidance has much in common with, but also sharp differences from, the influential 2018 guidelines on blood cholesterol management developed by the American College of Cardiology, American Heart Association, and 10 other medical societies.

And it is provocative enough to elicit at least four editorials issued the same day across the JAMA family of journals. They highlight key differences between the two documents, among them the USPSTF guidance’s consistent, narrow reliance on 7.5% and 10% cut points for 10-year risk levels as estimated from the ACC/AHA pooled cohort equations (PCE).  

The guidance pairs the 10-year risk metric with at least one of only four prescribed CV risk factors to arrive at a limited choice of statin therapy recommendations. But its decision process isn’t bolstered by coronary artery calcium (CAC) scores or the prespecified “risk enhancers” that allowed the ACC/AHA-multisociety guidelines to be applied broadly and still be closely personalized. Those guidelines provide more PCE-based risk tiers for greater discrimination of risk and allow statins to be considered across a broader age group.

The USPSTF guidance’s evidence base consists of 23 clinical trials and three observational studies that directly compared a statin to either placebo or no statin, task force member John B. Wong, MD, Tufts University School of Medicine, Boston, told this news organization.

“In either kind of study, we found that the vast majority of patients had one or more of four risk factors – dyslipidemia, hypertension, diabetes, or smoking. So, when we categorized high risk or increased risk, we included the presence of one or more of those risk factors,” said Dr. Wong, who is director of comparative effectiveness research at Tufts Clinical Translational Science Institute.
 

‘Sensible and practical’

The USPSTF guidance applies only to adults aged 40-75 without CV signs or symptoms and recommends a statin prescription for persons at “high risk,” that is with an estimated 10-year PCE-based risk for death or CV events of 10% or higher plus at least one of the four risk factors, a level B recommendation.

It recommends that “clinicians selectively offer a statin” to such persons at “increased risk,” who have at least one of the risk factors and an estimated 10-year risk for death or CV events of 7.5% to less than 10%, a level C recommendation. “The likelihood of benefit is smaller in this group” than in persons at high risk, the document states.

“These recommendations from the USPSTF are sensible and practical,” states Salim S. Virani, MD, PhD, DeBakey Veterans Affairs Medical Center, Houston, in a related editorial published the same day in JAMA Network Open. He calls the former B-level recommendation “a conservative approach” and the latter C-level recommendation a “nuanced approach.”

Both are “understandable” given that some studies suggest that the PCE may overestimate the CV risk, Dr. Virani observes. “On the other hand, statin therapy has been shown to be efficacious” at 10-year CV-risk levels down to about 5%.

The USPSTF document “I think is going to perpetuate a problem that we have in this country, which is vast undertreatment of lipids,” Eric D. Peterson, MD, MPH, University of Texas Southwestern Medical Center, Dallas, said in an interview.

“We have a ton of good drugs that can lower cholesterol like crazy. If you lower cholesterol a lot, you improve outcomes,” he said. Dyslipidemia needs to be more widely and consistently treated, but “right now we have a pool of people in primary prevention who undertreat lipids and wait until disease happens – and then cardiologists get engaged. That’s an avoidable miss,” Dr. Peterson adds. He and JAMA Cardiology associate editor Ann Marie Navar, MD, PhD, provided JAMA with an editorial that accompanies the USPSTF guidance.

“My own personal bias would be that the [ACC/AHA-multisociety guidelines] are closer to being right,” Dr. Peterson said. They – unlike the USPSTF guidance – cover people with risk levels below 7.5%, down to at least 5%. They allow risk enhancers like metabolic syndrome, inflammatory diseases, or family history into the decision process. “And they’re more aggressive in diabetes and more aggressive in older people,” he said.
 

Higher threshold for therapy

The USPSTF guidance also explicitly omits some high-risk groups and makes little accommodation for others who might especially benefit from statins, several of the editorials contend. For example, states a related JAMA Cardiology editorial published the same day, “The USPSTF does not comment on familial hypercholesterolemia or an LDL-C level of 190 mg/dL or higher,” yet they are covered by the ACC/AHA-multispecialty guidelines.

In addition, write the editorialists, led by Neil J. Stone, MD, Northwestern University, Chicago, “the USPSTF uses a slightly higher threshold for initiation of statin therapy” than was used in the ACC/AHA-multisociety guidelines. USPSTF, for example, calls for 10-year risk to reach 10% before recommending a statin prescription.

“One concern about the USPSTF setting the bar higher for statin initiation is that it reduces the number of young patients (age 40-50 years) at risk for premature myocardial infarction considered for treatment,” write Dr. Stone and colleagues.

That may be related to a weakness of the PCE-based decision process. “Because the PCE estimates of 10-year CV disease risk rely so heavily on age, sex, and race, use of these estimates to identify candidates for statins results in significant skewing of the population recommended for statins,” write Dr. Navar and Dr. Peterson in their JAMA editorial.

The risk enhancers in the ACC/AHA-multispecialty guidelines, about a dozen of them, compensate for that limitation to some extent. But the PCE-dominated USPSTF risk estimates will likely miss some groups that could potentially benefit from statin therapy, Dr. Peterson agreed in an interview.  

For example, younger adults facing years of high LDL-cholesterol levels could easily have PCE-based 10-year risk below 10%. “Having a high LDL over a lifetime puts you at really high risk,” he said. “Young people are missed even though their longitudinal risk is high.” So, by waiting for the lofty 10% level of risk over 10 years, “we limit the use of medicine that’s pretty cheap and highly effective.”

Dose intensity, adverse events

Also at variance from the ACC/AHA-multispecialty guidelines, the USPSTF states that, “Based on available evidence, use of moderate-intensity statin therapy seems reasonable for the primary prevention of CV disease in most persons.”  

The task force specifically explored whether evidence supports some use of high-intensity vs. moderate-intensity statins, Tufts University’s Dr. Wong said. “We found only one study that looked at that particular question, and it didn’t give us a strong answer.” An elevated rosuvastatin-related diabetes risk was apparent in the JUPITER trial, “but for the other studies, we did not find that association.”  

Most of the studies that explored statins for reducing risk for a first stroke or myocardial infarction used a moderate-dose statin, Dr. Wong said. “So that’s what we would usually recommend.”

But, Dr. Virani writes, consistent with the ACC/AHA-multispecialty guidelines, “clinicians should consider titrating the intensity of therapy to the risk of the individual.” Persons in certain high-risk primary prevention groups, such as those with end-organ injury from diabetes or LDL cholesterol at least 190 mg/dL, “may derive further benefit from the use of high-intensity statin therapy.”

Low-intensity statins are another potential option, but “in contrast with its 2016 recommendations, the USPSTF no longer recommends use of low-intensity statins in certain situations,” observes a fourth editorial published the same day in JAMA Internal Medicine, with lead author Anand R. Habib, MD, MPhil, and senior author Rita F. Redberg, MD, MSc, both of the University of California, San Francisco. Dr. Redberg is the journal’s editor and has long expressed cautions about statin safety.

“While it is understandable that the Task Force was limited by lack of data on dosing, this change is unfortunate for patients because the frequency of adverse effects increases as the statin dose increases,” the editorial states. Although USPSTF did not find statistically significant harm from the drugs, “in clinical practice, adverse events are commonly reported with use of statins.”

It continues: “At present, there are further reasons to curb our enthusiasm about the use of statins for primary prevention of CV disease.” To illustrate, the editorial questioned primary-prevention statins’ balance of risk vs. clinically meaningful benefit, not benefit that is merely statistically significant.

“The purported benefits of statins in terms of relative risk reduction are fairly constant across baseline lipid levels and cardiovascular risk score categories for primary prevention,” the editorial states.

“Therefore, the absolute benefit for those in lower-risk categories is likely small given that their baseline absolute risk is low, while the chance of adverse effects is constant across risk categories.”

However, USPSTF states, “In pooled analyses of trial data, statin therapy was not associated with increased risk of study withdrawal due to adverse events or serious adverse events.” Nor did it find significant associations with cancers, liver enzyme abnormalities, or diabetes, including new-onset diabetes.

And, the USPSTF adds, “Evidence on the association between statins and renal or cognitive harms is very limited but does not indicate increased risk.”

USPSTF is supported by the U.S. Agency for Healthcare Research and Quality. Dr. Virani discloses receiving grants from the Department of Veterans Affairs, National Institutes of Health, and the World Heart Federation; and personal fees from the American College of Cardiology. Dr. Peterson discloses serving on the JAMA editorial board and receiving research support to his institution from Amgen, Bristol-Myers Squibb, Esperion, and Janssen; and consulting fees from Novo Nordisk, Bayer, and Novartis. Dr. Navar discloses receiving research support to her institution from Amgen, Bristol-Myers Squibb, Esperion, and Janssen; and receiving honoraria and consulting fees from AstraZeneca, Boehringer Ingelheim, Bayer, Janssen, Lilly, Novo Nordisk, Novartis, New Amsterdam, and Pfizer. Dr. Stone discloses receiving an honorarium from Knowledge to Practice, an educational company not associated with the pharmaceutical industry; disclosures for the other authors are in the report. Dr. Redberg discloses receiving research funding from the Arnold Ventures Foundation and the Greenwall Foundation.

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

Questions about how to prescribe statins for primary prevention abound more than 3 decades after the drugs swept into clinical practice to become a first-line medical approach to cutting cardiovascular (CV) risk. Statin usage recommendations from different bodies can vary in ways both limited and fundamental, spurring the kind of debate that accompanies such a document newly issued by the United States Preventive Services Task Force.

The document, little changed from the draft guidance released for public comment in February, was published online Aug. 23 in JAMA and the USPSTF website. It replaces a similar document issued by the task force in 2016.

The guidance has much in common with, but also sharp differences from, the influential 2018 guidelines on blood cholesterol management developed by the American College of Cardiology, American Heart Association, and 10 other medical societies.

And it is provocative enough to elicit at least four editorials issued the same day across the JAMA family of journals. They highlight key differences between the two documents, among them the USPSTF guidance’s consistent, narrow reliance on 7.5% and 10% cut points for 10-year risk levels as estimated from the ACC/AHA pooled cohort equations (PCE).  

The guidance pairs the 10-year risk metric with at least one of only four prescribed CV risk factors to arrive at a limited choice of statin therapy recommendations. But its decision process isn’t bolstered by coronary artery calcium (CAC) scores or the prespecified “risk enhancers” that allowed the ACC/AHA-multisociety guidelines to be applied broadly and still be closely personalized. Those guidelines provide more PCE-based risk tiers for greater discrimination of risk and allow statins to be considered across a broader age group.

The USPSTF guidance’s evidence base consists of 23 clinical trials and three observational studies that directly compared a statin to either placebo or no statin, task force member John B. Wong, MD, Tufts University School of Medicine, Boston, told this news organization.

“In either kind of study, we found that the vast majority of patients had one or more of four risk factors – dyslipidemia, hypertension, diabetes, or smoking. So, when we categorized high risk or increased risk, we included the presence of one or more of those risk factors,” said Dr. Wong, who is director of comparative effectiveness research at Tufts Clinical Translational Science Institute.
 

‘Sensible and practical’

The USPSTF guidance applies only to adults aged 40-75 without CV signs or symptoms and recommends a statin prescription for persons at “high risk,” that is with an estimated 10-year PCE-based risk for death or CV events of 10% or higher plus at least one of the four risk factors, a level B recommendation.

It recommends that “clinicians selectively offer a statin” to such persons at “increased risk,” who have at least one of the risk factors and an estimated 10-year risk for death or CV events of 7.5% to less than 10%, a level C recommendation. “The likelihood of benefit is smaller in this group” than in persons at high risk, the document states.

“These recommendations from the USPSTF are sensible and practical,” states Salim S. Virani, MD, PhD, DeBakey Veterans Affairs Medical Center, Houston, in a related editorial published the same day in JAMA Network Open. He calls the former B-level recommendation “a conservative approach” and the latter C-level recommendation a “nuanced approach.”

Both are “understandable” given that some studies suggest that the PCE may overestimate the CV risk, Dr. Virani observes. “On the other hand, statin therapy has been shown to be efficacious” at 10-year CV-risk levels down to about 5%.

The USPSTF document “I think is going to perpetuate a problem that we have in this country, which is vast undertreatment of lipids,” Eric D. Peterson, MD, MPH, University of Texas Southwestern Medical Center, Dallas, said in an interview.

“We have a ton of good drugs that can lower cholesterol like crazy. If you lower cholesterol a lot, you improve outcomes,” he said. Dyslipidemia needs to be more widely and consistently treated, but “right now we have a pool of people in primary prevention who undertreat lipids and wait until disease happens – and then cardiologists get engaged. That’s an avoidable miss,” Dr. Peterson adds. He and JAMA Cardiology associate editor Ann Marie Navar, MD, PhD, provided JAMA with an editorial that accompanies the USPSTF guidance.

“My own personal bias would be that the [ACC/AHA-multisociety guidelines] are closer to being right,” Dr. Peterson said. They – unlike the USPSTF guidance – cover people with risk levels below 7.5%, down to at least 5%. They allow risk enhancers like metabolic syndrome, inflammatory diseases, or family history into the decision process. “And they’re more aggressive in diabetes and more aggressive in older people,” he said.
 

Higher threshold for therapy

The USPSTF guidance also explicitly omits some high-risk groups and makes little accommodation for others who might especially benefit from statins, several of the editorials contend. For example, states a related JAMA Cardiology editorial published the same day, “The USPSTF does not comment on familial hypercholesterolemia or an LDL-C level of 190 mg/dL or higher,” yet they are covered by the ACC/AHA-multispecialty guidelines.

In addition, write the editorialists, led by Neil J. Stone, MD, Northwestern University, Chicago, “the USPSTF uses a slightly higher threshold for initiation of statin therapy” than was used in the ACC/AHA-multisociety guidelines. USPSTF, for example, calls for 10-year risk to reach 10% before recommending a statin prescription.

“One concern about the USPSTF setting the bar higher for statin initiation is that it reduces the number of young patients (age 40-50 years) at risk for premature myocardial infarction considered for treatment,” write Dr. Stone and colleagues.

That may be related to a weakness of the PCE-based decision process. “Because the PCE estimates of 10-year CV disease risk rely so heavily on age, sex, and race, use of these estimates to identify candidates for statins results in significant skewing of the population recommended for statins,” write Dr. Navar and Dr. Peterson in their JAMA editorial.

The risk enhancers in the ACC/AHA-multispecialty guidelines, about a dozen of them, compensate for that limitation to some extent. But the PCE-dominated USPSTF risk estimates will likely miss some groups that could potentially benefit from statin therapy, Dr. Peterson agreed in an interview.  

For example, younger adults facing years of high LDL-cholesterol levels could easily have PCE-based 10-year risk below 10%. “Having a high LDL over a lifetime puts you at really high risk,” he said. “Young people are missed even though their longitudinal risk is high.” So, by waiting for the lofty 10% level of risk over 10 years, “we limit the use of medicine that’s pretty cheap and highly effective.”

Dose intensity, adverse events

Also at variance from the ACC/AHA-multispecialty guidelines, the USPSTF states that, “Based on available evidence, use of moderate-intensity statin therapy seems reasonable for the primary prevention of CV disease in most persons.”  

The task force specifically explored whether evidence supports some use of high-intensity vs. moderate-intensity statins, Tufts University’s Dr. Wong said. “We found only one study that looked at that particular question, and it didn’t give us a strong answer.” An elevated rosuvastatin-related diabetes risk was apparent in the JUPITER trial, “but for the other studies, we did not find that association.”  

Most of the studies that explored statins for reducing risk for a first stroke or myocardial infarction used a moderate-dose statin, Dr. Wong said. “So that’s what we would usually recommend.”

But, Dr. Virani writes, consistent with the ACC/AHA-multispecialty guidelines, “clinicians should consider titrating the intensity of therapy to the risk of the individual.” Persons in certain high-risk primary prevention groups, such as those with end-organ injury from diabetes or LDL cholesterol at least 190 mg/dL, “may derive further benefit from the use of high-intensity statin therapy.”

Low-intensity statins are another potential option, but “in contrast with its 2016 recommendations, the USPSTF no longer recommends use of low-intensity statins in certain situations,” observes a fourth editorial published the same day in JAMA Internal Medicine, with lead author Anand R. Habib, MD, MPhil, and senior author Rita F. Redberg, MD, MSc, both of the University of California, San Francisco. Dr. Redberg is the journal’s editor and has long expressed cautions about statin safety.

“While it is understandable that the Task Force was limited by lack of data on dosing, this change is unfortunate for patients because the frequency of adverse effects increases as the statin dose increases,” the editorial states. Although USPSTF did not find statistically significant harm from the drugs, “in clinical practice, adverse events are commonly reported with use of statins.”

It continues: “At present, there are further reasons to curb our enthusiasm about the use of statins for primary prevention of CV disease.” To illustrate, the editorial questioned primary-prevention statins’ balance of risk vs. clinically meaningful benefit, not benefit that is merely statistically significant.

“The purported benefits of statins in terms of relative risk reduction are fairly constant across baseline lipid levels and cardiovascular risk score categories for primary prevention,” the editorial states.

“Therefore, the absolute benefit for those in lower-risk categories is likely small given that their baseline absolute risk is low, while the chance of adverse effects is constant across risk categories.”

However, USPSTF states, “In pooled analyses of trial data, statin therapy was not associated with increased risk of study withdrawal due to adverse events or serious adverse events.” Nor did it find significant associations with cancers, liver enzyme abnormalities, or diabetes, including new-onset diabetes.

And, the USPSTF adds, “Evidence on the association between statins and renal or cognitive harms is very limited but does not indicate increased risk.”

USPSTF is supported by the U.S. Agency for Healthcare Research and Quality. Dr. Virani discloses receiving grants from the Department of Veterans Affairs, National Institutes of Health, and the World Heart Federation; and personal fees from the American College of Cardiology. Dr. Peterson discloses serving on the JAMA editorial board and receiving research support to his institution from Amgen, Bristol-Myers Squibb, Esperion, and Janssen; and consulting fees from Novo Nordisk, Bayer, and Novartis. Dr. Navar discloses receiving research support to her institution from Amgen, Bristol-Myers Squibb, Esperion, and Janssen; and receiving honoraria and consulting fees from AstraZeneca, Boehringer Ingelheim, Bayer, Janssen, Lilly, Novo Nordisk, Novartis, New Amsterdam, and Pfizer. Dr. Stone discloses receiving an honorarium from Knowledge to Practice, an educational company not associated with the pharmaceutical industry; disclosures for the other authors are in the report. Dr. Redberg discloses receiving research funding from the Arnold Ventures Foundation and the Greenwall Foundation.

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

Questions about how to prescribe statins for primary prevention abound more than 3 decades after the drugs swept into clinical practice to become a first-line medical approach to cutting cardiovascular (CV) risk. Statin usage recommendations from different bodies can vary in ways both limited and fundamental, spurring the kind of debate that accompanies such a document newly issued by the United States Preventive Services Task Force.

The document, little changed from the draft guidance released for public comment in February, was published online Aug. 23 in JAMA and the USPSTF website. It replaces a similar document issued by the task force in 2016.

The guidance has much in common with, but also sharp differences from, the influential 2018 guidelines on blood cholesterol management developed by the American College of Cardiology, American Heart Association, and 10 other medical societies.

And it is provocative enough to elicit at least four editorials issued the same day across the JAMA family of journals. They highlight key differences between the two documents, among them the USPSTF guidance’s consistent, narrow reliance on 7.5% and 10% cut points for 10-year risk levels as estimated from the ACC/AHA pooled cohort equations (PCE).  

The guidance pairs the 10-year risk metric with at least one of only four prescribed CV risk factors to arrive at a limited choice of statin therapy recommendations. But its decision process isn’t bolstered by coronary artery calcium (CAC) scores or the prespecified “risk enhancers” that allowed the ACC/AHA-multisociety guidelines to be applied broadly and still be closely personalized. Those guidelines provide more PCE-based risk tiers for greater discrimination of risk and allow statins to be considered across a broader age group.

The USPSTF guidance’s evidence base consists of 23 clinical trials and three observational studies that directly compared a statin to either placebo or no statin, task force member John B. Wong, MD, Tufts University School of Medicine, Boston, told this news organization.

“In either kind of study, we found that the vast majority of patients had one or more of four risk factors – dyslipidemia, hypertension, diabetes, or smoking. So, when we categorized high risk or increased risk, we included the presence of one or more of those risk factors,” said Dr. Wong, who is director of comparative effectiveness research at Tufts Clinical Translational Science Institute.
 

‘Sensible and practical’

The USPSTF guidance applies only to adults aged 40-75 without CV signs or symptoms and recommends a statin prescription for persons at “high risk,” that is with an estimated 10-year PCE-based risk for death or CV events of 10% or higher plus at least one of the four risk factors, a level B recommendation.

It recommends that “clinicians selectively offer a statin” to such persons at “increased risk,” who have at least one of the risk factors and an estimated 10-year risk for death or CV events of 7.5% to less than 10%, a level C recommendation. “The likelihood of benefit is smaller in this group” than in persons at high risk, the document states.

“These recommendations from the USPSTF are sensible and practical,” states Salim S. Virani, MD, PhD, DeBakey Veterans Affairs Medical Center, Houston, in a related editorial published the same day in JAMA Network Open. He calls the former B-level recommendation “a conservative approach” and the latter C-level recommendation a “nuanced approach.”

Both are “understandable” given that some studies suggest that the PCE may overestimate the CV risk, Dr. Virani observes. “On the other hand, statin therapy has been shown to be efficacious” at 10-year CV-risk levels down to about 5%.

The USPSTF document “I think is going to perpetuate a problem that we have in this country, which is vast undertreatment of lipids,” Eric D. Peterson, MD, MPH, University of Texas Southwestern Medical Center, Dallas, said in an interview.

“We have a ton of good drugs that can lower cholesterol like crazy. If you lower cholesterol a lot, you improve outcomes,” he said. Dyslipidemia needs to be more widely and consistently treated, but “right now we have a pool of people in primary prevention who undertreat lipids and wait until disease happens – and then cardiologists get engaged. That’s an avoidable miss,” Dr. Peterson adds. He and JAMA Cardiology associate editor Ann Marie Navar, MD, PhD, provided JAMA with an editorial that accompanies the USPSTF guidance.

“My own personal bias would be that the [ACC/AHA-multisociety guidelines] are closer to being right,” Dr. Peterson said. They – unlike the USPSTF guidance – cover people with risk levels below 7.5%, down to at least 5%. They allow risk enhancers like metabolic syndrome, inflammatory diseases, or family history into the decision process. “And they’re more aggressive in diabetes and more aggressive in older people,” he said.
 

Higher threshold for therapy

The USPSTF guidance also explicitly omits some high-risk groups and makes little accommodation for others who might especially benefit from statins, several of the editorials contend. For example, states a related JAMA Cardiology editorial published the same day, “The USPSTF does not comment on familial hypercholesterolemia or an LDL-C level of 190 mg/dL or higher,” yet they are covered by the ACC/AHA-multispecialty guidelines.

In addition, write the editorialists, led by Neil J. Stone, MD, Northwestern University, Chicago, “the USPSTF uses a slightly higher threshold for initiation of statin therapy” than was used in the ACC/AHA-multisociety guidelines. USPSTF, for example, calls for 10-year risk to reach 10% before recommending a statin prescription.

“One concern about the USPSTF setting the bar higher for statin initiation is that it reduces the number of young patients (age 40-50 years) at risk for premature myocardial infarction considered for treatment,” write Dr. Stone and colleagues.

That may be related to a weakness of the PCE-based decision process. “Because the PCE estimates of 10-year CV disease risk rely so heavily on age, sex, and race, use of these estimates to identify candidates for statins results in significant skewing of the population recommended for statins,” write Dr. Navar and Dr. Peterson in their JAMA editorial.

The risk enhancers in the ACC/AHA-multispecialty guidelines, about a dozen of them, compensate for that limitation to some extent. But the PCE-dominated USPSTF risk estimates will likely miss some groups that could potentially benefit from statin therapy, Dr. Peterson agreed in an interview.  

For example, younger adults facing years of high LDL-cholesterol levels could easily have PCE-based 10-year risk below 10%. “Having a high LDL over a lifetime puts you at really high risk,” he said. “Young people are missed even though their longitudinal risk is high.” So, by waiting for the lofty 10% level of risk over 10 years, “we limit the use of medicine that’s pretty cheap and highly effective.”

Dose intensity, adverse events

Also at variance from the ACC/AHA-multispecialty guidelines, the USPSTF states that, “Based on available evidence, use of moderate-intensity statin therapy seems reasonable for the primary prevention of CV disease in most persons.”  

The task force specifically explored whether evidence supports some use of high-intensity vs. moderate-intensity statins, Tufts University’s Dr. Wong said. “We found only one study that looked at that particular question, and it didn’t give us a strong answer.” An elevated rosuvastatin-related diabetes risk was apparent in the JUPITER trial, “but for the other studies, we did not find that association.”  

Most of the studies that explored statins for reducing risk for a first stroke or myocardial infarction used a moderate-dose statin, Dr. Wong said. “So that’s what we would usually recommend.”

But, Dr. Virani writes, consistent with the ACC/AHA-multispecialty guidelines, “clinicians should consider titrating the intensity of therapy to the risk of the individual.” Persons in certain high-risk primary prevention groups, such as those with end-organ injury from diabetes or LDL cholesterol at least 190 mg/dL, “may derive further benefit from the use of high-intensity statin therapy.”

Low-intensity statins are another potential option, but “in contrast with its 2016 recommendations, the USPSTF no longer recommends use of low-intensity statins in certain situations,” observes a fourth editorial published the same day in JAMA Internal Medicine, with lead author Anand R. Habib, MD, MPhil, and senior author Rita F. Redberg, MD, MSc, both of the University of California, San Francisco. Dr. Redberg is the journal’s editor and has long expressed cautions about statin safety.

“While it is understandable that the Task Force was limited by lack of data on dosing, this change is unfortunate for patients because the frequency of adverse effects increases as the statin dose increases,” the editorial states. Although USPSTF did not find statistically significant harm from the drugs, “in clinical practice, adverse events are commonly reported with use of statins.”

It continues: “At present, there are further reasons to curb our enthusiasm about the use of statins for primary prevention of CV disease.” To illustrate, the editorial questioned primary-prevention statins’ balance of risk vs. clinically meaningful benefit, not benefit that is merely statistically significant.

“The purported benefits of statins in terms of relative risk reduction are fairly constant across baseline lipid levels and cardiovascular risk score categories for primary prevention,” the editorial states.

“Therefore, the absolute benefit for those in lower-risk categories is likely small given that their baseline absolute risk is low, while the chance of adverse effects is constant across risk categories.”

However, USPSTF states, “In pooled analyses of trial data, statin therapy was not associated with increased risk of study withdrawal due to adverse events or serious adverse events.” Nor did it find significant associations with cancers, liver enzyme abnormalities, or diabetes, including new-onset diabetes.

And, the USPSTF adds, “Evidence on the association between statins and renal or cognitive harms is very limited but does not indicate increased risk.”

USPSTF is supported by the U.S. Agency for Healthcare Research and Quality. Dr. Virani discloses receiving grants from the Department of Veterans Affairs, National Institutes of Health, and the World Heart Federation; and personal fees from the American College of Cardiology. Dr. Peterson discloses serving on the JAMA editorial board and receiving research support to his institution from Amgen, Bristol-Myers Squibb, Esperion, and Janssen; and consulting fees from Novo Nordisk, Bayer, and Novartis. Dr. Navar discloses receiving research support to her institution from Amgen, Bristol-Myers Squibb, Esperion, and Janssen; and receiving honoraria and consulting fees from AstraZeneca, Boehringer Ingelheim, Bayer, Janssen, Lilly, Novo Nordisk, Novartis, New Amsterdam, and Pfizer. Dr. Stone discloses receiving an honorarium from Knowledge to Practice, an educational company not associated with the pharmaceutical industry; disclosures for the other authors are in the report. Dr. Redberg discloses receiving research funding from the Arnold Ventures Foundation and the Greenwall Foundation.

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

Updated clinical practice guidelines for the treatment and prevention of venous thromboembolism for patients with cancer, including those with cancer and COVID-19, have been released by the International Initiative on Thrombosis and Cancer (ITAC), an academic working group of VTE experts.

“Because patients with cancer have a baseline increased risk of VTE, compared with patients without cancer, the combination of both COVID-19 and cancer – and its effect on VTE risk and treatment – is of concern,” said the authors, led by Dominique Farge, MD, PhD, Nord Universite de Paris.

The updated 2022 ITAC guidelines cover new evidence on the treatment and prophylaxis of cancer-associated thrombosis, including for patients with cancer and COVID-19, they added.

The new guidelines were published online in The Lancet Oncology.

“Cancer-associated VTE remains an important clinical problem, associated with increased morbidity and mortality,” Dr. Farge and colleagues observed.

“The ITAC guidelines’ companion free web-based mobile application will assist the practicing clinician with decision making at various levels to provide optimal care of patients with cancer to treat and prevent VTE,” they emphasized. More information is available at itaccme.com.
 

Cancer patients with COVID

The new section of the guidelines notes that the treatment and prevention of VTE for cancer patients infected with SARS-CoV-2 remain the same as for patients without COVID.

Whether or not cancer patients with COVID-19 are hospitalized, have been discharged, or are ambulatory, they should be assessed for the risk of VTE, as should any other patient. For cancer patients with COVID-19 who are hospitalized, pharmacologic prophylaxis should be given at the same dose and anticoagulant type as for hospitalized cancer patients who do not have COVID-19.

Following discharge, VTE prophylaxis is not advised for cancer patients infected with SARS-CoV-2, and routine primary pharmacologic prophylaxis of VTE for ambulatory patients with COVID-19 is also not recommended, the authors noted.
 

Initial treatment of established VTE

Initial treatment of established VTE for up to 10 days of anticoagulation should include low-molecular-weight heparin (LMWH) when creatinine clearance is at least 30 mL/min.

“A regimen of LMWH, taken once per day, is recommended unless a twice-per-day regimen is required because of patients’ characteristics,” the authors noted. These characteristics include a high risk of bleeding, moderate renal failure, and the need for technical intervention, including surgery.

If a twice-a-day regimen is required, only enoxaparin at a dose of 1 mg/kg twice daily can be used, the authors cautioned.

For patients with a low risk of gastrointestinal or genitourinary bleeding, rivaroxaban (Xarelto) or apixaban (Eliquis) can be given in the first 10 days, as well as edoxaban (Lixiana). The latter should be started after at least 5 days of parenteral anticoagulation, provided creatinine clearance is at least 30 mL/min.

“Unfractionated heparin as well as fondaparinux (GlaxoSmithKline) can be also used for the initial treatment of established VTE when LMWH or direct oral anticoagulants are contraindicated,” Dr. Farge and colleagues wrote.

Thrombolysis can be considered on a case-by-case basis, although physicians must pay attention to specific contraindications, especially bleeding risk.

“In the initial treatment of VTE, inferior vena cava filters might be considered when anticoagulant treatment is contraindicated or, in the case of pulmonary embolism, when recurrence occurs under optimal anticoagulation,” the authors noted.
 

Maintenance VTE treatment

For maintenance therapy, which the authors define as early maintenance for up to 6 months and long-term maintenance beyond 6 months, they point out that LMWHs are preferred over vitamin K antagonists for the treatment of VTE when the creatinine clearance is again at least 30 mL/min.

Any of the direct oral anticoagulants (DOAs) – edoxaban, rivaroxaban, or apixaban – is also recommended for the same patients, provided there is no risk of inducing a strong drug-drug interaction or GI absorption is impaired.

However, the DOAs should be used with caution for patients with GI malignancies, especially upper GI cancers, because data show there is an increased risk of GI bleeding with both edoxaban and rivaroxaban.

“LMWH or direct oral anticoagulants should be used for a minimum of 6 months to treat established VTE in patients with cancer,” the authors wrote.

“After 6 months, termination or continuation of anticoagulation (LMWH, direct oral anticoagulants, or vitamin K antagonists) should be based on individual evaluation of the benefit-risk ratio,” they added.
 

Treatment of VTE recurrence

The guideline authors explain that three options can be considered in the event of VTE recurrence. These include an increase in the LMWH dose by 20%-25%, or a switch to a DOA, or, if patients are taking a DOA, a switch to an LMWH. If the patient is taking a vitamin K antagonist, it can be switched to either an LMWH or a DOA.

For treatment of catheter-related thrombosis, anticoagulant treatment is recommended for a minimum of 3 months and as long as the central venous catheter is in place. In this setting, the LMWHs are recommended.

The central venous catheter can be kept in place if it is functional, well positioned, and is not infected, provided there is good resolution of symptoms under close surveillance while anticoagulants are being administered.

In surgically treated patients, the LMWH, given once a day, to patients with a serum creatinine concentration of at least 30 mL/min can be used to prevent VTE. Alternatively, VTE can be prevented by the use low-dose unfractionated heparin, given three times a day.

“Pharmacological prophylaxis should be started 2-12 h preoperatively and continued for at least 7–10 days,” Dr. Farge and colleagues advised. In this setting, there is insufficient evidence to support the use of fondaparinux or a DOA as an alternative to an LMWH for the prophylaxis of postoperative VTE. “Use of the highest prophylactic dose of LMWH to prevent postoperative VTE in patients with cancer is recommended,” the authors advised.

Furthermore, extended prophylaxis of at least 4 weeks with LMWH is advised to prevent postoperative VTE after major abdominal or pelvic surgery. Mechanical methods are not recommended except when pharmacologic methods are contraindicated. Inferior vena cava filters are also not recommended for routine prophylaxis.
 

Patients with reduced mobility

For medically treated hospitalized patients with cancer whose mobility is reduced, the authors recommend prophylaxis with either an LMWH or fondaparinux, provided their creatinine clearance is at least 30 mL/min. These patients can also be treated with unfractionated heparin, they add.

In contrast, DOAs are not recommended – at least not routinely – in this setting, the authors cautioned. Primary pharmacologic prophylaxis of VTE with either LMWH or DOAs – either rivaroxaban or apixaban – is indicated in ambulatory patients with locally advanced or metastatic pancreatic cancer who are receiving systemic anticancer therapy, provided they are at low risk of bleeding.

However, primary pharmacologic prophylaxis with LMWH is not recommended outside of a clinical trial for patients with locally advanced or metastatic lung cancer who are undergoing systemic anticancer therapy, even for patients who are at low risk of bleeding.

For ambulatory patients who are receiving systemic anticancer therapy and who are at intermediate risk of VTE, primary prophylaxis with rivaroxaban or apixaban is recommended for those with myeloma who are receiving immunomodulatory therapy plus steroids or other systemic therapies.

In this setting, oral anticoagulants should consist of a vitamin K antagonist, given at low or therapeutic doses, or apixaban, given at prophylactic doses. Alternatively, LMWH, given at prophylactic doses, or low-dose aspirin, given at a dose of 100 mg/day, can be used.
 

Catheter-related thrombosis

Use of anticoagulation for routine prophylaxis of catheter-related thrombosis is not recommended. Catheters should be inserted on the right side in the jugular vein, and the distal extremity of the central catheter should be located at the junction of the superior vena cava and the right atrium. “In patients requiring central venous catheters, we suggest the use of implanted ports over peripheral inserted central catheter lines,” the authors noted.

The authors described a number of unique situations regarding the treatment of VTE. These situations include patients with a brain tumor, for whom treatment of established VTE should favor either LMWH or a DOA. The authors also recommended the use of LMWH or unfractionated heparin, started postoperatively, for the prevention of VTE for patients undergoing neurosurgery.

In contrast, pharmacologic prophylaxis of VTE in medically treated patients with a brain tumor who are not undergoing neurosurgery is not recommended. “In the presence of severe renal failure...we suggest using unfractionated heparin followed by early vitamin K antagonists (possibly from day 1) or LMWH adjusted to anti-Xa concentration of the treatment of established VTE,” Dr. Farge and colleagues wrote.

Anticoagulant treatment is also recommended for a minimum of 3 months for children with symptomatic catheter-related thrombosis and as long as the central venous catheter is in place. For children with acute lymphoblastic leukemia who are undergoing induction chemotherapy, LMWH is also recommended as thromboprophylaxis.

For children who require a central venous catheter, the authors suggested that physicians use implanted ports over peripherally inserted central lines.

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

Updated clinical practice guidelines for the treatment and prevention of venous thromboembolism for patients with cancer, including those with cancer and COVID-19, have been released by the International Initiative on Thrombosis and Cancer (ITAC), an academic working group of VTE experts.

“Because patients with cancer have a baseline increased risk of VTE, compared with patients without cancer, the combination of both COVID-19 and cancer – and its effect on VTE risk and treatment – is of concern,” said the authors, led by Dominique Farge, MD, PhD, Nord Universite de Paris.

The updated 2022 ITAC guidelines cover new evidence on the treatment and prophylaxis of cancer-associated thrombosis, including for patients with cancer and COVID-19, they added.

The new guidelines were published online in The Lancet Oncology.

“Cancer-associated VTE remains an important clinical problem, associated with increased morbidity and mortality,” Dr. Farge and colleagues observed.

“The ITAC guidelines’ companion free web-based mobile application will assist the practicing clinician with decision making at various levels to provide optimal care of patients with cancer to treat and prevent VTE,” they emphasized. More information is available at itaccme.com.
 

Cancer patients with COVID

The new section of the guidelines notes that the treatment and prevention of VTE for cancer patients infected with SARS-CoV-2 remain the same as for patients without COVID.

Whether or not cancer patients with COVID-19 are hospitalized, have been discharged, or are ambulatory, they should be assessed for the risk of VTE, as should any other patient. For cancer patients with COVID-19 who are hospitalized, pharmacologic prophylaxis should be given at the same dose and anticoagulant type as for hospitalized cancer patients who do not have COVID-19.

Following discharge, VTE prophylaxis is not advised for cancer patients infected with SARS-CoV-2, and routine primary pharmacologic prophylaxis of VTE for ambulatory patients with COVID-19 is also not recommended, the authors noted.
 

Initial treatment of established VTE

Initial treatment of established VTE for up to 10 days of anticoagulation should include low-molecular-weight heparin (LMWH) when creatinine clearance is at least 30 mL/min.

“A regimen of LMWH, taken once per day, is recommended unless a twice-per-day regimen is required because of patients’ characteristics,” the authors noted. These characteristics include a high risk of bleeding, moderate renal failure, and the need for technical intervention, including surgery.

If a twice-a-day regimen is required, only enoxaparin at a dose of 1 mg/kg twice daily can be used, the authors cautioned.

For patients with a low risk of gastrointestinal or genitourinary bleeding, rivaroxaban (Xarelto) or apixaban (Eliquis) can be given in the first 10 days, as well as edoxaban (Lixiana). The latter should be started after at least 5 days of parenteral anticoagulation, provided creatinine clearance is at least 30 mL/min.

“Unfractionated heparin as well as fondaparinux (GlaxoSmithKline) can be also used for the initial treatment of established VTE when LMWH or direct oral anticoagulants are contraindicated,” Dr. Farge and colleagues wrote.

Thrombolysis can be considered on a case-by-case basis, although physicians must pay attention to specific contraindications, especially bleeding risk.

“In the initial treatment of VTE, inferior vena cava filters might be considered when anticoagulant treatment is contraindicated or, in the case of pulmonary embolism, when recurrence occurs under optimal anticoagulation,” the authors noted.
 

Maintenance VTE treatment

For maintenance therapy, which the authors define as early maintenance for up to 6 months and long-term maintenance beyond 6 months, they point out that LMWHs are preferred over vitamin K antagonists for the treatment of VTE when the creatinine clearance is again at least 30 mL/min.

Any of the direct oral anticoagulants (DOAs) – edoxaban, rivaroxaban, or apixaban – is also recommended for the same patients, provided there is no risk of inducing a strong drug-drug interaction or GI absorption is impaired.

However, the DOAs should be used with caution for patients with GI malignancies, especially upper GI cancers, because data show there is an increased risk of GI bleeding with both edoxaban and rivaroxaban.

“LMWH or direct oral anticoagulants should be used for a minimum of 6 months to treat established VTE in patients with cancer,” the authors wrote.

“After 6 months, termination or continuation of anticoagulation (LMWH, direct oral anticoagulants, or vitamin K antagonists) should be based on individual evaluation of the benefit-risk ratio,” they added.
 

Treatment of VTE recurrence

The guideline authors explain that three options can be considered in the event of VTE recurrence. These include an increase in the LMWH dose by 20%-25%, or a switch to a DOA, or, if patients are taking a DOA, a switch to an LMWH. If the patient is taking a vitamin K antagonist, it can be switched to either an LMWH or a DOA.

For treatment of catheter-related thrombosis, anticoagulant treatment is recommended for a minimum of 3 months and as long as the central venous catheter is in place. In this setting, the LMWHs are recommended.

The central venous catheter can be kept in place if it is functional, well positioned, and is not infected, provided there is good resolution of symptoms under close surveillance while anticoagulants are being administered.

In surgically treated patients, the LMWH, given once a day, to patients with a serum creatinine concentration of at least 30 mL/min can be used to prevent VTE. Alternatively, VTE can be prevented by the use low-dose unfractionated heparin, given three times a day.

“Pharmacological prophylaxis should be started 2-12 h preoperatively and continued for at least 7–10 days,” Dr. Farge and colleagues advised. In this setting, there is insufficient evidence to support the use of fondaparinux or a DOA as an alternative to an LMWH for the prophylaxis of postoperative VTE. “Use of the highest prophylactic dose of LMWH to prevent postoperative VTE in patients with cancer is recommended,” the authors advised.

Furthermore, extended prophylaxis of at least 4 weeks with LMWH is advised to prevent postoperative VTE after major abdominal or pelvic surgery. Mechanical methods are not recommended except when pharmacologic methods are contraindicated. Inferior vena cava filters are also not recommended for routine prophylaxis.
 

Patients with reduced mobility

For medically treated hospitalized patients with cancer whose mobility is reduced, the authors recommend prophylaxis with either an LMWH or fondaparinux, provided their creatinine clearance is at least 30 mL/min. These patients can also be treated with unfractionated heparin, they add.

In contrast, DOAs are not recommended – at least not routinely – in this setting, the authors cautioned. Primary pharmacologic prophylaxis of VTE with either LMWH or DOAs – either rivaroxaban or apixaban – is indicated in ambulatory patients with locally advanced or metastatic pancreatic cancer who are receiving systemic anticancer therapy, provided they are at low risk of bleeding.

However, primary pharmacologic prophylaxis with LMWH is not recommended outside of a clinical trial for patients with locally advanced or metastatic lung cancer who are undergoing systemic anticancer therapy, even for patients who are at low risk of bleeding.

For ambulatory patients who are receiving systemic anticancer therapy and who are at intermediate risk of VTE, primary prophylaxis with rivaroxaban or apixaban is recommended for those with myeloma who are receiving immunomodulatory therapy plus steroids or other systemic therapies.

In this setting, oral anticoagulants should consist of a vitamin K antagonist, given at low or therapeutic doses, or apixaban, given at prophylactic doses. Alternatively, LMWH, given at prophylactic doses, or low-dose aspirin, given at a dose of 100 mg/day, can be used.
 

Catheter-related thrombosis

Use of anticoagulation for routine prophylaxis of catheter-related thrombosis is not recommended. Catheters should be inserted on the right side in the jugular vein, and the distal extremity of the central catheter should be located at the junction of the superior vena cava and the right atrium. “In patients requiring central venous catheters, we suggest the use of implanted ports over peripheral inserted central catheter lines,” the authors noted.

The authors described a number of unique situations regarding the treatment of VTE. These situations include patients with a brain tumor, for whom treatment of established VTE should favor either LMWH or a DOA. The authors also recommended the use of LMWH or unfractionated heparin, started postoperatively, for the prevention of VTE for patients undergoing neurosurgery.

In contrast, pharmacologic prophylaxis of VTE in medically treated patients with a brain tumor who are not undergoing neurosurgery is not recommended. “In the presence of severe renal failure...we suggest using unfractionated heparin followed by early vitamin K antagonists (possibly from day 1) or LMWH adjusted to anti-Xa concentration of the treatment of established VTE,” Dr. Farge and colleagues wrote.

Anticoagulant treatment is also recommended for a minimum of 3 months for children with symptomatic catheter-related thrombosis and as long as the central venous catheter is in place. For children with acute lymphoblastic leukemia who are undergoing induction chemotherapy, LMWH is also recommended as thromboprophylaxis.

For children who require a central venous catheter, the authors suggested that physicians use implanted ports over peripherally inserted central lines.

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

Updated clinical practice guidelines for the treatment and prevention of venous thromboembolism for patients with cancer, including those with cancer and COVID-19, have been released by the International Initiative on Thrombosis and Cancer (ITAC), an academic working group of VTE experts.

“Because patients with cancer have a baseline increased risk of VTE, compared with patients without cancer, the combination of both COVID-19 and cancer – and its effect on VTE risk and treatment – is of concern,” said the authors, led by Dominique Farge, MD, PhD, Nord Universite de Paris.

The updated 2022 ITAC guidelines cover new evidence on the treatment and prophylaxis of cancer-associated thrombosis, including for patients with cancer and COVID-19, they added.

The new guidelines were published online in The Lancet Oncology.

“Cancer-associated VTE remains an important clinical problem, associated with increased morbidity and mortality,” Dr. Farge and colleagues observed.

“The ITAC guidelines’ companion free web-based mobile application will assist the practicing clinician with decision making at various levels to provide optimal care of patients with cancer to treat and prevent VTE,” they emphasized. More information is available at itaccme.com.
 

Cancer patients with COVID

The new section of the guidelines notes that the treatment and prevention of VTE for cancer patients infected with SARS-CoV-2 remain the same as for patients without COVID.

Whether or not cancer patients with COVID-19 are hospitalized, have been discharged, or are ambulatory, they should be assessed for the risk of VTE, as should any other patient. For cancer patients with COVID-19 who are hospitalized, pharmacologic prophylaxis should be given at the same dose and anticoagulant type as for hospitalized cancer patients who do not have COVID-19.

Following discharge, VTE prophylaxis is not advised for cancer patients infected with SARS-CoV-2, and routine primary pharmacologic prophylaxis of VTE for ambulatory patients with COVID-19 is also not recommended, the authors noted.
 

Initial treatment of established VTE

Initial treatment of established VTE for up to 10 days of anticoagulation should include low-molecular-weight heparin (LMWH) when creatinine clearance is at least 30 mL/min.

“A regimen of LMWH, taken once per day, is recommended unless a twice-per-day regimen is required because of patients’ characteristics,” the authors noted. These characteristics include a high risk of bleeding, moderate renal failure, and the need for technical intervention, including surgery.

If a twice-a-day regimen is required, only enoxaparin at a dose of 1 mg/kg twice daily can be used, the authors cautioned.

For patients with a low risk of gastrointestinal or genitourinary bleeding, rivaroxaban (Xarelto) or apixaban (Eliquis) can be given in the first 10 days, as well as edoxaban (Lixiana). The latter should be started after at least 5 days of parenteral anticoagulation, provided creatinine clearance is at least 30 mL/min.

“Unfractionated heparin as well as fondaparinux (GlaxoSmithKline) can be also used for the initial treatment of established VTE when LMWH or direct oral anticoagulants are contraindicated,” Dr. Farge and colleagues wrote.

Thrombolysis can be considered on a case-by-case basis, although physicians must pay attention to specific contraindications, especially bleeding risk.

“In the initial treatment of VTE, inferior vena cava filters might be considered when anticoagulant treatment is contraindicated or, in the case of pulmonary embolism, when recurrence occurs under optimal anticoagulation,” the authors noted.
 

Maintenance VTE treatment

For maintenance therapy, which the authors define as early maintenance for up to 6 months and long-term maintenance beyond 6 months, they point out that LMWHs are preferred over vitamin K antagonists for the treatment of VTE when the creatinine clearance is again at least 30 mL/min.

Any of the direct oral anticoagulants (DOAs) – edoxaban, rivaroxaban, or apixaban – is also recommended for the same patients, provided there is no risk of inducing a strong drug-drug interaction or GI absorption is impaired.

However, the DOAs should be used with caution for patients with GI malignancies, especially upper GI cancers, because data show there is an increased risk of GI bleeding with both edoxaban and rivaroxaban.

“LMWH or direct oral anticoagulants should be used for a minimum of 6 months to treat established VTE in patients with cancer,” the authors wrote.

“After 6 months, termination or continuation of anticoagulation (LMWH, direct oral anticoagulants, or vitamin K antagonists) should be based on individual evaluation of the benefit-risk ratio,” they added.
 

Treatment of VTE recurrence

The guideline authors explain that three options can be considered in the event of VTE recurrence. These include an increase in the LMWH dose by 20%-25%, or a switch to a DOA, or, if patients are taking a DOA, a switch to an LMWH. If the patient is taking a vitamin K antagonist, it can be switched to either an LMWH or a DOA.

For treatment of catheter-related thrombosis, anticoagulant treatment is recommended for a minimum of 3 months and as long as the central venous catheter is in place. In this setting, the LMWHs are recommended.

The central venous catheter can be kept in place if it is functional, well positioned, and is not infected, provided there is good resolution of symptoms under close surveillance while anticoagulants are being administered.

In surgically treated patients, the LMWH, given once a day, to patients with a serum creatinine concentration of at least 30 mL/min can be used to prevent VTE. Alternatively, VTE can be prevented by the use low-dose unfractionated heparin, given three times a day.

“Pharmacological prophylaxis should be started 2-12 h preoperatively and continued for at least 7–10 days,” Dr. Farge and colleagues advised. In this setting, there is insufficient evidence to support the use of fondaparinux or a DOA as an alternative to an LMWH for the prophylaxis of postoperative VTE. “Use of the highest prophylactic dose of LMWH to prevent postoperative VTE in patients with cancer is recommended,” the authors advised.

Furthermore, extended prophylaxis of at least 4 weeks with LMWH is advised to prevent postoperative VTE after major abdominal or pelvic surgery. Mechanical methods are not recommended except when pharmacologic methods are contraindicated. Inferior vena cava filters are also not recommended for routine prophylaxis.
 

Patients with reduced mobility

For medically treated hospitalized patients with cancer whose mobility is reduced, the authors recommend prophylaxis with either an LMWH or fondaparinux, provided their creatinine clearance is at least 30 mL/min. These patients can also be treated with unfractionated heparin, they add.

In contrast, DOAs are not recommended – at least not routinely – in this setting, the authors cautioned. Primary pharmacologic prophylaxis of VTE with either LMWH or DOAs – either rivaroxaban or apixaban – is indicated in ambulatory patients with locally advanced or metastatic pancreatic cancer who are receiving systemic anticancer therapy, provided they are at low risk of bleeding.

However, primary pharmacologic prophylaxis with LMWH is not recommended outside of a clinical trial for patients with locally advanced or metastatic lung cancer who are undergoing systemic anticancer therapy, even for patients who are at low risk of bleeding.

For ambulatory patients who are receiving systemic anticancer therapy and who are at intermediate risk of VTE, primary prophylaxis with rivaroxaban or apixaban is recommended for those with myeloma who are receiving immunomodulatory therapy plus steroids or other systemic therapies.

In this setting, oral anticoagulants should consist of a vitamin K antagonist, given at low or therapeutic doses, or apixaban, given at prophylactic doses. Alternatively, LMWH, given at prophylactic doses, or low-dose aspirin, given at a dose of 100 mg/day, can be used.
 

Catheter-related thrombosis

Use of anticoagulation for routine prophylaxis of catheter-related thrombosis is not recommended. Catheters should be inserted on the right side in the jugular vein, and the distal extremity of the central catheter should be located at the junction of the superior vena cava and the right atrium. “In patients requiring central venous catheters, we suggest the use of implanted ports over peripheral inserted central catheter lines,” the authors noted.

The authors described a number of unique situations regarding the treatment of VTE. These situations include patients with a brain tumor, for whom treatment of established VTE should favor either LMWH or a DOA. The authors also recommended the use of LMWH or unfractionated heparin, started postoperatively, for the prevention of VTE for patients undergoing neurosurgery.

In contrast, pharmacologic prophylaxis of VTE in medically treated patients with a brain tumor who are not undergoing neurosurgery is not recommended. “In the presence of severe renal failure...we suggest using unfractionated heparin followed by early vitamin K antagonists (possibly from day 1) or LMWH adjusted to anti-Xa concentration of the treatment of established VTE,” Dr. Farge and colleagues wrote.

Anticoagulant treatment is also recommended for a minimum of 3 months for children with symptomatic catheter-related thrombosis and as long as the central venous catheter is in place. For children with acute lymphoblastic leukemia who are undergoing induction chemotherapy, LMWH is also recommended as thromboprophylaxis.

For children who require a central venous catheter, the authors suggested that physicians use implanted ports over peripherally inserted central lines.

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

Patients with rheumatic and musculoskeletal diseases may need additional vaccines or different versions of vaccines they were not previously recommended to receive, according to updated guidelines from the American College of Rheumatology (ACR) on vaccinations for these patients. The new guidelines pertain to routine vaccinations for adults and children and are based on the most current evidence. They include recommendations on whether to hold certain medications before or after vaccination. They do not include recommendations regarding COVID-19 vaccines.

For guidance on COVID-19 vaccine timing and frequency, the ACR directs physicians to the CDC’s recommendations for people with mild or severe immunosuppression and the ACR’s previous clinical guidance summary on the topic, last revised in February 2022. The recommendations in the new guidance differ from ACR’s guidance on COVID-19 vaccines on whether and when to hold immunosuppressive medications when patients receive nonlive vaccines. The new guidelines now align more closely with those of EULAR, the Infectious Diseases Society of America, and the CDC’s recommendations for human papillomavirus (HPV), pneumococcal, and shingles vaccines.

MarianVejcik/Getty Images

Vaccinations in this population are particularly important because “a leading cause of morbidity and mortality in those with rheumatic diseases is infections, due to the detrimental impact immunosuppression has on the ability for the patient to properly clear the pathogen,” Alfred Kim, MD, PhD, professor of rheumatology at Washington University, St. Louis, told this news organization. While immunosuppressive medications are the most common reason patients with these conditions may have impaired immune function, “some of our patients with autoimmune disease also have a preexisting immunodeficiency that can inherently blunt immune responses to either infection or vaccination,” Dr. Kim explained.

“The authors of the guidelines have done a really nice job of making distinct recommendations based on the mechanism of action of various immunosuppressive medications,” Dr. Kim said. “This helps simplify the process of deciding the timing of vaccination for the health provider, especially for those on multiple immunosuppressives who represent an important proportion of our patients with rheumatic diseases.”

The main change to the guidelines for children, aside from those related to flu vaccination, is in regard to rotavirus vaccination for infants exposed to tumor necrosis factor (TNF) inhibitors or rituximab in utero. Infants prenatally exposed to rituximab should not receive the rotavirus vaccine until they are older than 6 months. Those exposed prenatally to TNF inhibitors should receive the rotavirus vaccine on time, according to the CDC schedule for all infants.

The new rotavirus recommendations follow data showing that immune responses to rotavirus are blunted in those with infliximab exposure, according to Dr. Kim.

“Thus, this poses a serious theoretical risk in newborns with mothers on [a TNF inhibitor] of ineffective clearance of rotavirus infections,” Dr. Kim said in an interview. “While rotavirus infections are quite common with typically self-limiting disease, sometimes requiring hydration to counteract diarrhea-induced dehydration, this can become severe in these newborns that have [a TNF inhibitor] in their system.”

For adults, the ACR issued the following expanded indications for four vaccines for patients currently taking immunosuppressive medication:

• Patients aged 18 and older should receive the recombinant zoster vaccine against shingles.
• For patients aged 27-44 who weren’t previously vaccinated against HPV, the HPV vaccine is “conditionally recommended.”
• Patients younger than 65 should receive the pneumococcal vaccine.
• Patients aged 19-64 are conditionally recommended to receive the high-dose or adjuvanted flu vaccine rather than the regular-dose flu vaccine.

The guidelines also conditionally recommend that all patients aged 65 and older who have rheumatic or musculoskeletal diseases receive the high-dose or adjuvanted flu vaccine, regardless of whether they are taking immunosuppressive medication. Another new conditional recommendation is to give multiple vaccinations to patients on the same day, rather than give individual vaccines on different days.

The guidelines make conditional recommendations regarding flu and nonlive attenuated vaccines for those taking methotrexate, rituximab, or glucocorticoids. Methotrexate should be held for 2 weeks after flu vaccination as long as disease activity allows it, but patients who are taking methotrexate should continue taking it for any other nonlive attenuated vaccinations.

“Non-rheumatology providers, such as general pediatricians and internists, are encouraged to give the influenza vaccination and then consult with the patient’s rheumatology provider about holding methotrexate to avoid a missed vaccination opportunity,” the guidelines state.

Patients taking rituximab should receive the flu vaccine on schedule and continue taking rituximab. However, for these patients, the guidelines recommend to “delay any subsequent rituximab dosing for at least two weeks after influenza vaccination if disease activity allows.”

“Because of the relatively short time period between the rollout of the influenza vaccine and its season, we can’t always wait to time the B-cell depletion dosage,” Dr. Kim said. “Also, it is not always easy to synchronize the patient’s B-cell depletion dosing schedule to the influenza vaccine rollout. Thus, we now just recommend getting the influenza vaccine regardless of the patient’s last B-cell depletion dosage despite its known strong attenuation of optimal immune responses.”

For other nonlive attenuated vaccines, providers should time vaccination for when the next rituximab dose is due and then hold the drug for at least 2 weeks thereafter, providing time for the B cells to mount a response before rituximab depletes B cells again.

Patients taking less than 20 mg of prednisone daily should still receive the flu vaccine and other nonlive attenuated vaccines. Those taking 20 mg or more of prednisone each day should still receive the flu vaccine, but other vaccines should be deferred until their dose of glucocorticoids has been tapered down to less than 20 mg daily.

Patients taking all other immunosuppressive medications should continue taking them for the flu vaccine and other nonlive attenuated vaccinations, but it is conditionally recommended that live attenuated vaccines be deferred. For any patient with a rheumatic and musculoskeletal disease, regardless of disease activity, it is conditionally recommended that all routine nonlive attenuated vaccines be administered.

For live attenuated virus vaccines, the ACR provides a chart on which immunosuppressive medications to hold and for how long. Glucocorticoids, methotrexate, azathioprine, leflunomide, mycophenolate mofetil, calcineurin inhibitors, and oral cyclophosphamide should all be held 4 weeks before and 4 weeks after administration of a live attenuated vaccine. For those taking JAK inhibitors, the medication should be halted 1 week before administration of a live vaccine and should continue to be withheld for 4 weeks after.

For most other biologics, the ACR recommends holding the medication for one dosing interval before the live vaccine and 4 weeks thereafter. The main exception is rituximab, which should be held for 6 months before a live vaccine and then for 4 more weeks thereafter.

For patients receiving intravenous immunoglobulin, the drug should be held for 8-11 months before they are administered a live attenuated vaccine, depending on the dosage, and then 4 weeks after vaccination, regardless of dosage.

To reassure people with rheumatic disease who may have anxiety or concerns about receiving immunizations, whether taking immunosuppressive medication or not, Dr. Kim said it’s important to provide lots of education to patients.

“Fear and emotion have replaced facts, and data as a leading factor in decision-making, as seen with COVID-19,” Dr. Kim said. “The reality is that a small minority of people will have any issues with most vaccines, which include disease flares, adverse events, or acquisition of an autoimmune disease. We are not saying there is zero risk, rather, that the risk is quite small. This is where shared decision-making between the health care provider and the patient must be done effectively to enable the patient to properly weigh risk versus benefit.”

Dr. Kim has relationships with GlaxoSmithKline, Aurinia Pharmaceuticals, Kypha, Pfizer, Alexion Pharmaceuticals, AstraZeneca, Exagen Diagnostics, and Foghorn Therapeutics.

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

Patients with rheumatic and musculoskeletal diseases may need additional vaccines or different versions of vaccines they were not previously recommended to receive, according to updated guidelines from the American College of Rheumatology (ACR) on vaccinations for these patients. The new guidelines pertain to routine vaccinations for adults and children and are based on the most current evidence. They include recommendations on whether to hold certain medications before or after vaccination. They do not include recommendations regarding COVID-19 vaccines.

For guidance on COVID-19 vaccine timing and frequency, the ACR directs physicians to the CDC’s recommendations for people with mild or severe immunosuppression and the ACR’s previous clinical guidance summary on the topic, last revised in February 2022. The recommendations in the new guidance differ from ACR’s guidance on COVID-19 vaccines on whether and when to hold immunosuppressive medications when patients receive nonlive vaccines. The new guidelines now align more closely with those of EULAR, the Infectious Diseases Society of America, and the CDC’s recommendations for human papillomavirus (HPV), pneumococcal, and shingles vaccines.

MarianVejcik/Getty Images

Vaccinations in this population are particularly important because “a leading cause of morbidity and mortality in those with rheumatic diseases is infections, due to the detrimental impact immunosuppression has on the ability for the patient to properly clear the pathogen,” Alfred Kim, MD, PhD, professor of rheumatology at Washington University, St. Louis, told this news organization. While immunosuppressive medications are the most common reason patients with these conditions may have impaired immune function, “some of our patients with autoimmune disease also have a preexisting immunodeficiency that can inherently blunt immune responses to either infection or vaccination,” Dr. Kim explained.

“The authors of the guidelines have done a really nice job of making distinct recommendations based on the mechanism of action of various immunosuppressive medications,” Dr. Kim said. “This helps simplify the process of deciding the timing of vaccination for the health provider, especially for those on multiple immunosuppressives who represent an important proportion of our patients with rheumatic diseases.”

The main change to the guidelines for children, aside from those related to flu vaccination, is in regard to rotavirus vaccination for infants exposed to tumor necrosis factor (TNF) inhibitors or rituximab in utero. Infants prenatally exposed to rituximab should not receive the rotavirus vaccine until they are older than 6 months. Those exposed prenatally to TNF inhibitors should receive the rotavirus vaccine on time, according to the CDC schedule for all infants.

The new rotavirus recommendations follow data showing that immune responses to rotavirus are blunted in those with infliximab exposure, according to Dr. Kim.

“Thus, this poses a serious theoretical risk in newborns with mothers on [a TNF inhibitor] of ineffective clearance of rotavirus infections,” Dr. Kim said in an interview. “While rotavirus infections are quite common with typically self-limiting disease, sometimes requiring hydration to counteract diarrhea-induced dehydration, this can become severe in these newborns that have [a TNF inhibitor] in their system.”

For adults, the ACR issued the following expanded indications for four vaccines for patients currently taking immunosuppressive medication:

• Patients aged 18 and older should receive the recombinant zoster vaccine against shingles.
• For patients aged 27-44 who weren’t previously vaccinated against HPV, the HPV vaccine is “conditionally recommended.”
• Patients younger than 65 should receive the pneumococcal vaccine.
• Patients aged 19-64 are conditionally recommended to receive the high-dose or adjuvanted flu vaccine rather than the regular-dose flu vaccine.

The guidelines also conditionally recommend that all patients aged 65 and older who have rheumatic or musculoskeletal diseases receive the high-dose or adjuvanted flu vaccine, regardless of whether they are taking immunosuppressive medication. Another new conditional recommendation is to give multiple vaccinations to patients on the same day, rather than give individual vaccines on different days.

The guidelines make conditional recommendations regarding flu and nonlive attenuated vaccines for those taking methotrexate, rituximab, or glucocorticoids. Methotrexate should be held for 2 weeks after flu vaccination as long as disease activity allows it, but patients who are taking methotrexate should continue taking it for any other nonlive attenuated vaccinations.

“Non-rheumatology providers, such as general pediatricians and internists, are encouraged to give the influenza vaccination and then consult with the patient’s rheumatology provider about holding methotrexate to avoid a missed vaccination opportunity,” the guidelines state.

Patients taking rituximab should receive the flu vaccine on schedule and continue taking rituximab. However, for these patients, the guidelines recommend to “delay any subsequent rituximab dosing for at least two weeks after influenza vaccination if disease activity allows.”

“Because of the relatively short time period between the rollout of the influenza vaccine and its season, we can’t always wait to time the B-cell depletion dosage,” Dr. Kim said. “Also, it is not always easy to synchronize the patient’s B-cell depletion dosing schedule to the influenza vaccine rollout. Thus, we now just recommend getting the influenza vaccine regardless of the patient’s last B-cell depletion dosage despite its known strong attenuation of optimal immune responses.”

For other nonlive attenuated vaccines, providers should time vaccination for when the next rituximab dose is due and then hold the drug for at least 2 weeks thereafter, providing time for the B cells to mount a response before rituximab depletes B cells again.

Patients taking less than 20 mg of prednisone daily should still receive the flu vaccine and other nonlive attenuated vaccines. Those taking 20 mg or more of prednisone each day should still receive the flu vaccine, but other vaccines should be deferred until their dose of glucocorticoids has been tapered down to less than 20 mg daily.

Patients taking all other immunosuppressive medications should continue taking them for the flu vaccine and other nonlive attenuated vaccinations, but it is conditionally recommended that live attenuated vaccines be deferred. For any patient with a rheumatic and musculoskeletal disease, regardless of disease activity, it is conditionally recommended that all routine nonlive attenuated vaccines be administered.

For live attenuated virus vaccines, the ACR provides a chart on which immunosuppressive medications to hold and for how long. Glucocorticoids, methotrexate, azathioprine, leflunomide, mycophenolate mofetil, calcineurin inhibitors, and oral cyclophosphamide should all be held 4 weeks before and 4 weeks after administration of a live attenuated vaccine. For those taking JAK inhibitors, the medication should be halted 1 week before administration of a live vaccine and should continue to be withheld for 4 weeks after.

For most other biologics, the ACR recommends holding the medication for one dosing interval before the live vaccine and 4 weeks thereafter. The main exception is rituximab, which should be held for 6 months before a live vaccine and then for 4 more weeks thereafter.

For patients receiving intravenous immunoglobulin, the drug should be held for 8-11 months before they are administered a live attenuated vaccine, depending on the dosage, and then 4 weeks after vaccination, regardless of dosage.

To reassure people with rheumatic disease who may have anxiety or concerns about receiving immunizations, whether taking immunosuppressive medication or not, Dr. Kim said it’s important to provide lots of education to patients.

“Fear and emotion have replaced facts, and data as a leading factor in decision-making, as seen with COVID-19,” Dr. Kim said. “The reality is that a small minority of people will have any issues with most vaccines, which include disease flares, adverse events, or acquisition of an autoimmune disease. We are not saying there is zero risk, rather, that the risk is quite small. This is where shared decision-making between the health care provider and the patient must be done effectively to enable the patient to properly weigh risk versus benefit.”

Dr. Kim has relationships with GlaxoSmithKline, Aurinia Pharmaceuticals, Kypha, Pfizer, Alexion Pharmaceuticals, AstraZeneca, Exagen Diagnostics, and Foghorn Therapeutics.

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

Patients with rheumatic and musculoskeletal diseases may need additional vaccines or different versions of vaccines they were not previously recommended to receive, according to updated guidelines from the American College of Rheumatology (ACR) on vaccinations for these patients. The new guidelines pertain to routine vaccinations for adults and children and are based on the most current evidence. They include recommendations on whether to hold certain medications before or after vaccination. They do not include recommendations regarding COVID-19 vaccines.

For guidance on COVID-19 vaccine timing and frequency, the ACR directs physicians to the CDC’s recommendations for people with mild or severe immunosuppression and the ACR’s previous clinical guidance summary on the topic, last revised in February 2022. The recommendations in the new guidance differ from ACR’s guidance on COVID-19 vaccines on whether and when to hold immunosuppressive medications when patients receive nonlive vaccines. The new guidelines now align more closely with those of EULAR, the Infectious Diseases Society of America, and the CDC’s recommendations for human papillomavirus (HPV), pneumococcal, and shingles vaccines.

MarianVejcik/Getty Images

Vaccinations in this population are particularly important because “a leading cause of morbidity and mortality in those with rheumatic diseases is infections, due to the detrimental impact immunosuppression has on the ability for the patient to properly clear the pathogen,” Alfred Kim, MD, PhD, professor of rheumatology at Washington University, St. Louis, told this news organization. While immunosuppressive medications are the most common reason patients with these conditions may have impaired immune function, “some of our patients with autoimmune disease also have a preexisting immunodeficiency that can inherently blunt immune responses to either infection or vaccination,” Dr. Kim explained.

“The authors of the guidelines have done a really nice job of making distinct recommendations based on the mechanism of action of various immunosuppressive medications,” Dr. Kim said. “This helps simplify the process of deciding the timing of vaccination for the health provider, especially for those on multiple immunosuppressives who represent an important proportion of our patients with rheumatic diseases.”

The main change to the guidelines for children, aside from those related to flu vaccination, is in regard to rotavirus vaccination for infants exposed to tumor necrosis factor (TNF) inhibitors or rituximab in utero. Infants prenatally exposed to rituximab should not receive the rotavirus vaccine until they are older than 6 months. Those exposed prenatally to TNF inhibitors should receive the rotavirus vaccine on time, according to the CDC schedule for all infants.

The new rotavirus recommendations follow data showing that immune responses to rotavirus are blunted in those with infliximab exposure, according to Dr. Kim.

“Thus, this poses a serious theoretical risk in newborns with mothers on [a TNF inhibitor] of ineffective clearance of rotavirus infections,” Dr. Kim said in an interview. “While rotavirus infections are quite common with typically self-limiting disease, sometimes requiring hydration to counteract diarrhea-induced dehydration, this can become severe in these newborns that have [a TNF inhibitor] in their system.”

For adults, the ACR issued the following expanded indications for four vaccines for patients currently taking immunosuppressive medication:

• Patients aged 18 and older should receive the recombinant zoster vaccine against shingles.
• For patients aged 27-44 who weren’t previously vaccinated against HPV, the HPV vaccine is “conditionally recommended.”
• Patients younger than 65 should receive the pneumococcal vaccine.
• Patients aged 19-64 are conditionally recommended to receive the high-dose or adjuvanted flu vaccine rather than the regular-dose flu vaccine.

The guidelines also conditionally recommend that all patients aged 65 and older who have rheumatic or musculoskeletal diseases receive the high-dose or adjuvanted flu vaccine, regardless of whether they are taking immunosuppressive medication. Another new conditional recommendation is to give multiple vaccinations to patients on the same day, rather than give individual vaccines on different days.

The guidelines make conditional recommendations regarding flu and nonlive attenuated vaccines for those taking methotrexate, rituximab, or glucocorticoids. Methotrexate should be held for 2 weeks after flu vaccination as long as disease activity allows it, but patients who are taking methotrexate should continue taking it for any other nonlive attenuated vaccinations.

“Non-rheumatology providers, such as general pediatricians and internists, are encouraged to give the influenza vaccination and then consult with the patient’s rheumatology provider about holding methotrexate to avoid a missed vaccination opportunity,” the guidelines state.

Patients taking rituximab should receive the flu vaccine on schedule and continue taking rituximab. However, for these patients, the guidelines recommend to “delay any subsequent rituximab dosing for at least two weeks after influenza vaccination if disease activity allows.”

“Because of the relatively short time period between the rollout of the influenza vaccine and its season, we can’t always wait to time the B-cell depletion dosage,” Dr. Kim said. “Also, it is not always easy to synchronize the patient’s B-cell depletion dosing schedule to the influenza vaccine rollout. Thus, we now just recommend getting the influenza vaccine regardless of the patient’s last B-cell depletion dosage despite its known strong attenuation of optimal immune responses.”

For other nonlive attenuated vaccines, providers should time vaccination for when the next rituximab dose is due and then hold the drug for at least 2 weeks thereafter, providing time for the B cells to mount a response before rituximab depletes B cells again.

Patients taking less than 20 mg of prednisone daily should still receive the flu vaccine and other nonlive attenuated vaccines. Those taking 20 mg or more of prednisone each day should still receive the flu vaccine, but other vaccines should be deferred until their dose of glucocorticoids has been tapered down to less than 20 mg daily.

Patients taking all other immunosuppressive medications should continue taking them for the flu vaccine and other nonlive attenuated vaccinations, but it is conditionally recommended that live attenuated vaccines be deferred. For any patient with a rheumatic and musculoskeletal disease, regardless of disease activity, it is conditionally recommended that all routine nonlive attenuated vaccines be administered.

For live attenuated virus vaccines, the ACR provides a chart on which immunosuppressive medications to hold and for how long. Glucocorticoids, methotrexate, azathioprine, leflunomide, mycophenolate mofetil, calcineurin inhibitors, and oral cyclophosphamide should all be held 4 weeks before and 4 weeks after administration of a live attenuated vaccine. For those taking JAK inhibitors, the medication should be halted 1 week before administration of a live vaccine and should continue to be withheld for 4 weeks after.

For most other biologics, the ACR recommends holding the medication for one dosing interval before the live vaccine and 4 weeks thereafter. The main exception is rituximab, which should be held for 6 months before a live vaccine and then for 4 more weeks thereafter.

For patients receiving intravenous immunoglobulin, the drug should be held for 8-11 months before they are administered a live attenuated vaccine, depending on the dosage, and then 4 weeks after vaccination, regardless of dosage.

To reassure people with rheumatic disease who may have anxiety or concerns about receiving immunizations, whether taking immunosuppressive medication or not, Dr. Kim said it’s important to provide lots of education to patients.

“Fear and emotion have replaced facts, and data as a leading factor in decision-making, as seen with COVID-19,” Dr. Kim said. “The reality is that a small minority of people will have any issues with most vaccines, which include disease flares, adverse events, or acquisition of an autoimmune disease. We are not saying there is zero risk, rather, that the risk is quite small. This is where shared decision-making between the health care provider and the patient must be done effectively to enable the patient to properly weigh risk versus benefit.”

Dr. Kim has relationships with GlaxoSmithKline, Aurinia Pharmaceuticals, Kypha, Pfizer, Alexion Pharmaceuticals, AstraZeneca, Exagen Diagnostics, and Foghorn Therapeutics.

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

Hormone therapy remains a topic for debate, but a constant in the 2 decades since the Women’s Health Initiative has been the demonstrated effectiveness for relief of vasomotor symptoms and reduction of fracture risk in menopausal women, according to the latest hormone therapy position statement of the North American Menopause Society.

“Healthcare professionals caring for menopausal women should understand the basic concepts of relative risk and absolute risk,” wrote Stephanie S. Faubion, MD, director of the Mayo Clinic Center for Women’s Health and medical director of NAMS, and members of the NAMS 2022 Hormone Therapy Position Statement Advisory Panel in Menopause.

The authors noted that the risks of hormone therapy vary considerably based on type, dose, duration, route of administration, timing of the start of therapy, and whether or not a progestogen is included.

The 2022 statement was commissioned to review new literature and identify the strength of recommendations and quality of evidence since the previous statement in 2017.

The current statement represents not so much a practice-changing update, “but rather that the literature has filled out in some areas,” Dr. Faubion said in an interview. “The recommendations overall haven’t changed,” she said. “The position statement reiterates that hormone therapy, which is significantly underutilized, remains a safe and effective treatment for menopause symptoms, which remain undertreated, with the benefits outweighing the risks for most healthy women who are within 10 years of menopause onset and under the age of 60 years,” she emphasized. “Individualizing therapy is key to maximizing benefits and minimizing risks,” she added.

Overall, the authors confirmed that hormone therapy remains the most effective treatment for vasomotor symptoms (VMS) and the genitourinary syndrome of menopause (GSM), and has been shown to prevent bone loss and fracture. The risks of hormone therapy differ depending on type, dose, duration of use, route of administration, timing of initiation, and whether a progestogen is used.

Risks and benefits should be stratified by age and time since the start of menopause, according to the statement.

For women younger than 60 years or within 10 years of the onset of menopause who have no contraindications, the potential benefits outweigh the risks in most cases for use of hormone therapy to manage vasomotor symptoms and to help prevent bone loss and reduce fracture risk.

For women who begin hormone therapy more than 10 or 20 years from the start of menopause, or who are aged 60 years and older, the risk-benefit ratio may be less favorable because of the increased absolute risk of coronary heart disease, stroke, venous thromboembolism, and dementia. However, strategies such as lower doses and transdermal administration may reduce this risk, according to the statement.

The authors continue to recommend that longer durations of hormone therapy be for documented indications, such as VMS relief, and that patients on longer duration of therapy be reassessed periodically as part of a shared decision-making process. Women with persistent VMS or quality of life issues, or those at risk for osteoporosis, may continue hormone therapy beyond age 60 or 65 years after appropriate evaluation and risk-benefit counseling.

Women with ongoing GSM without indications for systemic therapy whose GSM persists after over-the-counter therapies may try low-dose vaginal estrogen or other nonestrogen therapies regardless of age and for an extended duration if needed, according to the statement.
 

Challenges, research gaps, and goals

“Barriers to the use of hormone therapy include lack of access to high quality care,” Dr. Faubion said in an interview. The NAMS website, menopause.org, features an option to search for a NAMS-certified provider by ZIP code, she noted.

“Coverage of hormone therapy is highly variable and depends on the insurance company, but most women have access to one form or another with insurance coverage,” she said. “We need to continue to advocate for adequate coverage of menopause symptom treatments, including hormone therapy, so that women’s symptoms – which can significantly affect quality of life – are adequately managed.

“Additional research is needed on the thrombotic risk (venous thromboembolism, pulmonary embolism, and stroke) of oral versus transdermal therapies (including different formulations, doses, and durations of therapy),” Dr. Faubion told this news organization. “More clinical trial data are needed to confirm or refute the potential beneficial effects of hormone therapy on coronary heart disease and all-cause mortality when initiated in perimenopause or early postmenopause,” she said.

Other areas for research include “the breast effects of different estrogen preparations, including the role for selective estrogen receptor modulator (SERM) and tissue selective estrogen complex therapies, optimal progestogen or SERM regimens to prevent endometrial hyperplasia, the relationship between vasomotor symptoms and the risk for heart disease and cognitive changes, and the risks of premature ovarian insufficiency,” Dr. Faubion emphasized.

Looking ahead, “Studies are needed on the effects of longer use of low-dose vaginal estrogen therapy after breast or endometrial cancer, extended use of hormone therapy in women who are early initiators, improved tools to personalize or individualize benefits and risks of hormone therapy, and the role of aging and genetics,” said Dr. Faubion. Other areas for further research include “the long-term benefits and risks on women’s health of lifestyle modification or complementary or nonhormone therapies, if chosen in addition to or over hormone therapy for vasomotor symptoms, bone health, and cardiovascular disease risk reduction,” she added.

The complete statement was published in Menopause: The Journal of the North American Menopause Society.

The position statement received no outside funding. The authors had no financial conflicts to disclose.

Hormone therapy remains a topic for debate, but a constant in the 2 decades since the Women’s Health Initiative has been the demonstrated effectiveness for relief of vasomotor symptoms and reduction of fracture risk in menopausal women, according to the latest hormone therapy position statement of the North American Menopause Society.

“Healthcare professionals caring for menopausal women should understand the basic concepts of relative risk and absolute risk,” wrote Stephanie S. Faubion, MD, director of the Mayo Clinic Center for Women’s Health and medical director of NAMS, and members of the NAMS 2022 Hormone Therapy Position Statement Advisory Panel in Menopause.

The authors noted that the risks of hormone therapy vary considerably based on type, dose, duration, route of administration, timing of the start of therapy, and whether or not a progestogen is included.

The 2022 statement was commissioned to review new literature and identify the strength of recommendations and quality of evidence since the previous statement in 2017.

The current statement represents not so much a practice-changing update, “but rather that the literature has filled out in some areas,” Dr. Faubion said in an interview. “The recommendations overall haven’t changed,” she said. “The position statement reiterates that hormone therapy, which is significantly underutilized, remains a safe and effective treatment for menopause symptoms, which remain undertreated, with the benefits outweighing the risks for most healthy women who are within 10 years of menopause onset and under the age of 60 years,” she emphasized. “Individualizing therapy is key to maximizing benefits and minimizing risks,” she added.

Overall, the authors confirmed that hormone therapy remains the most effective treatment for vasomotor symptoms (VMS) and the genitourinary syndrome of menopause (GSM), and has been shown to prevent bone loss and fracture. The risks of hormone therapy differ depending on type, dose, duration of use, route of administration, timing of initiation, and whether a progestogen is used.

Risks and benefits should be stratified by age and time since the start of menopause, according to the statement.

For women younger than 60 years or within 10 years of the onset of menopause who have no contraindications, the potential benefits outweigh the risks in most cases for use of hormone therapy to manage vasomotor symptoms and to help prevent bone loss and reduce fracture risk.

For women who begin hormone therapy more than 10 or 20 years from the start of menopause, or who are aged 60 years and older, the risk-benefit ratio may be less favorable because of the increased absolute risk of coronary heart disease, stroke, venous thromboembolism, and dementia. However, strategies such as lower doses and transdermal administration may reduce this risk, according to the statement.

The authors continue to recommend that longer durations of hormone therapy be for documented indications, such as VMS relief, and that patients on longer duration of therapy be reassessed periodically as part of a shared decision-making process. Women with persistent VMS or quality of life issues, or those at risk for osteoporosis, may continue hormone therapy beyond age 60 or 65 years after appropriate evaluation and risk-benefit counseling.

Women with ongoing GSM without indications for systemic therapy whose GSM persists after over-the-counter therapies may try low-dose vaginal estrogen or other nonestrogen therapies regardless of age and for an extended duration if needed, according to the statement.
 

Challenges, research gaps, and goals

“Barriers to the use of hormone therapy include lack of access to high quality care,” Dr. Faubion said in an interview. The NAMS website, menopause.org, features an option to search for a NAMS-certified provider by ZIP code, she noted.

“Coverage of hormone therapy is highly variable and depends on the insurance company, but most women have access to one form or another with insurance coverage,” she said. “We need to continue to advocate for adequate coverage of menopause symptom treatments, including hormone therapy, so that women’s symptoms – which can significantly affect quality of life – are adequately managed.

“Additional research is needed on the thrombotic risk (venous thromboembolism, pulmonary embolism, and stroke) of oral versus transdermal therapies (including different formulations, doses, and durations of therapy),” Dr. Faubion told this news organization. “More clinical trial data are needed to confirm or refute the potential beneficial effects of hormone therapy on coronary heart disease and all-cause mortality when initiated in perimenopause or early postmenopause,” she said.

Other areas for research include “the breast effects of different estrogen preparations, including the role for selective estrogen receptor modulator (SERM) and tissue selective estrogen complex therapies, optimal progestogen or SERM regimens to prevent endometrial hyperplasia, the relationship between vasomotor symptoms and the risk for heart disease and cognitive changes, and the risks of premature ovarian insufficiency,” Dr. Faubion emphasized.

Looking ahead, “Studies are needed on the effects of longer use of low-dose vaginal estrogen therapy after breast or endometrial cancer, extended use of hormone therapy in women who are early initiators, improved tools to personalize or individualize benefits and risks of hormone therapy, and the role of aging and genetics,” said Dr. Faubion. Other areas for further research include “the long-term benefits and risks on women’s health of lifestyle modification or complementary or nonhormone therapies, if chosen in addition to or over hormone therapy for vasomotor symptoms, bone health, and cardiovascular disease risk reduction,” she added.

The complete statement was published in Menopause: The Journal of the North American Menopause Society.

The position statement received no outside funding. The authors had no financial conflicts to disclose.

Hormone therapy remains a topic for debate, but a constant in the 2 decades since the Women’s Health Initiative has been the demonstrated effectiveness for relief of vasomotor symptoms and reduction of fracture risk in menopausal women, according to the latest hormone therapy position statement of the North American Menopause Society.

“Healthcare professionals caring for menopausal women should understand the basic concepts of relative risk and absolute risk,” wrote Stephanie S. Faubion, MD, director of the Mayo Clinic Center for Women’s Health and medical director of NAMS, and members of the NAMS 2022 Hormone Therapy Position Statement Advisory Panel in Menopause.

The authors noted that the risks of hormone therapy vary considerably based on type, dose, duration, route of administration, timing of the start of therapy, and whether or not a progestogen is included.

The 2022 statement was commissioned to review new literature and identify the strength of recommendations and quality of evidence since the previous statement in 2017.

The current statement represents not so much a practice-changing update, “but rather that the literature has filled out in some areas,” Dr. Faubion said in an interview. “The recommendations overall haven’t changed,” she said. “The position statement reiterates that hormone therapy, which is significantly underutilized, remains a safe and effective treatment for menopause symptoms, which remain undertreated, with the benefits outweighing the risks for most healthy women who are within 10 years of menopause onset and under the age of 60 years,” she emphasized. “Individualizing therapy is key to maximizing benefits and minimizing risks,” she added.

Overall, the authors confirmed that hormone therapy remains the most effective treatment for vasomotor symptoms (VMS) and the genitourinary syndrome of menopause (GSM), and has been shown to prevent bone loss and fracture. The risks of hormone therapy differ depending on type, dose, duration of use, route of administration, timing of initiation, and whether a progestogen is used.

Risks and benefits should be stratified by age and time since the start of menopause, according to the statement.

For women younger than 60 years or within 10 years of the onset of menopause who have no contraindications, the potential benefits outweigh the risks in most cases for use of hormone therapy to manage vasomotor symptoms and to help prevent bone loss and reduce fracture risk.

For women who begin hormone therapy more than 10 or 20 years from the start of menopause, or who are aged 60 years and older, the risk-benefit ratio may be less favorable because of the increased absolute risk of coronary heart disease, stroke, venous thromboembolism, and dementia. However, strategies such as lower doses and transdermal administration may reduce this risk, according to the statement.

The authors continue to recommend that longer durations of hormone therapy be for documented indications, such as VMS relief, and that patients on longer duration of therapy be reassessed periodically as part of a shared decision-making process. Women with persistent VMS or quality of life issues, or those at risk for osteoporosis, may continue hormone therapy beyond age 60 or 65 years after appropriate evaluation and risk-benefit counseling.

Women with ongoing GSM without indications for systemic therapy whose GSM persists after over-the-counter therapies may try low-dose vaginal estrogen or other nonestrogen therapies regardless of age and for an extended duration if needed, according to the statement.
 

Challenges, research gaps, and goals

“Barriers to the use of hormone therapy include lack of access to high quality care,” Dr. Faubion said in an interview. The NAMS website, menopause.org, features an option to search for a NAMS-certified provider by ZIP code, she noted.

“Coverage of hormone therapy is highly variable and depends on the insurance company, but most women have access to one form or another with insurance coverage,” she said. “We need to continue to advocate for adequate coverage of menopause symptom treatments, including hormone therapy, so that women’s symptoms – which can significantly affect quality of life – are adequately managed.

“Additional research is needed on the thrombotic risk (venous thromboembolism, pulmonary embolism, and stroke) of oral versus transdermal therapies (including different formulations, doses, and durations of therapy),” Dr. Faubion told this news organization. “More clinical trial data are needed to confirm or refute the potential beneficial effects of hormone therapy on coronary heart disease and all-cause mortality when initiated in perimenopause or early postmenopause,” she said.

Other areas for research include “the breast effects of different estrogen preparations, including the role for selective estrogen receptor modulator (SERM) and tissue selective estrogen complex therapies, optimal progestogen or SERM regimens to prevent endometrial hyperplasia, the relationship between vasomotor symptoms and the risk for heart disease and cognitive changes, and the risks of premature ovarian insufficiency,” Dr. Faubion emphasized.

Looking ahead, “Studies are needed on the effects of longer use of low-dose vaginal estrogen therapy after breast or endometrial cancer, extended use of hormone therapy in women who are early initiators, improved tools to personalize or individualize benefits and risks of hormone therapy, and the role of aging and genetics,” said Dr. Faubion. Other areas for further research include “the long-term benefits and risks on women’s health of lifestyle modification or complementary or nonhormone therapies, if chosen in addition to or over hormone therapy for vasomotor symptoms, bone health, and cardiovascular disease risk reduction,” she added.

The complete statement was published in Menopause: The Journal of the North American Menopause Society.

The position statement received no outside funding. The authors had no financial conflicts to disclose.

Raising phototherapy thresholds and revising risk assessment are among the key changes in the American Academy of Pediatrics’ updated guidelines for managing hyperbilirubinemia in infants 35 weeks’ gestation and older.

“More than 80% of newborn infants will have some degree of jaundice,” Alex R. Kemper, MD, of Nationwide Children’s Hospital, Columbus, Ohio, and coauthors wrote. Careful monitoring is needed manage high bilirubin concentrations and avoid acute bilirubin encephalopathy (ABE) and kernicterus, a disabling neurologic condition.

The current revision, published in Pediatrics, updates and replaces the 2004 AAP clinical practice guidelines for the management and prevention of hyperbilirubinemia in newborns of at least 35 weeks’ gestation.

The guideline committee reviewed evidence published since the previous guidelines were issued in 2004, and addressed similar issues of prevention, risk assessment, monitoring, and treatment.

A notable change from 2004 was the inclusion of a 2009 recommendation update for “universal predischarge bilirubin screening with measures of total serum bilirubin (TSB) or transcutaneous bilirubin (TcB) linked to specific recommendations for follow-up,” the authors wrote.

In terms of prevention, recommendations include a direct antiglobulin test (DAT) for infants whose mother’s antibody screen was positive or unknown. In addition, exclusive breastfeeding is known to be associated with hyperbilirubinemia, but clinicians should support breastfeeding while monitoring for signs of hyperbilirubinemia because of suboptimal feeding, the authors noted. However, the guidelines recommend against oral supplementation with water or dextrose water to prevent hyperbilirubinemia.

For assessment and monitoring, the guidelines advise the use of total serum bilirubin (TSB) as the definitive test for hyperbilirubinemia to guide phototherapy and escalation of care, including exchange transfusion. “The presence of hyperbilirubinemia neurotoxicity risk factors lowers the threshold for treatment with phototherapy and the level at which care should be escalated,” the authors wrote. They also emphasized the need to consider glucose-6-phosphate dehydrogenase deficiency, a genetic condition that decreases protection against oxidative stress and has been identified as a leading cause of hazardous hyperbilirubinemia worldwide.

The guidelines recommend assessing all infants for jaundice at least every 12 hours after delivery until discharge, with TSB or TcB measured as soon as possible for those with suspected jaundice. The complete guidelines include charts for TSB levels to guide escalation of care. “Blood for TSB can be obtained at the time it is collected for newborn screening tests to avoid an additional heel stick,” the authors noted.

The rate of increase in TSB or TcB, if more than one measure is available, may identify infants at higher risk of hyperbilirubinemia, according to the guidelines, and a possible delay of hospital discharge may be needed for infants if appropriate follow-up is not feasible.

In terms of treatment, new evidence that bilirubin neurotoxicity does not occur until concentrations well above those given in the 2004 guidelines justified raising the treatment thresholds, although by a narrow range. “With the increased phototherapy thresholds, appropriately following the current guidelines including bilirubin screening during the birth hospitalization and timely postdischarge follow-up is important,” the authors wrote. The new thresholds, outlined in the complete guidelines, are based on gestational age, hyperbilirubinemia neurotoxicity risk factors, and the age of the infant in hours. However, infants may be treated at lower levels, based on individual circumstances, family preferences, and shared decision-making with clinicians. Home-based phototherapy may be used in some infants, but should not be used if there is a question about the device quality, delivery time, and ability of caregivers to use the device correctly.

“Discontinuing phototherapy is an option when the TSB has decreased by at least 2 mg/dL below the hour-specific threshold at the initiation of phototherapy,” and follow-up should be based on risk of rebound hyperbilirubinemia, according to the guidelines.

“This clinical practice guideline provides indications and approaches for phototherapy and escalation of care and when treatment and monitoring can be safely discontinued,” However, clinicians should understand the rationale for the recommendations and combine them with their clinical judgment, including shared decision-making when appropriate, the authors concluded.
 

Updated evidence supports escalating care

The take-home message for pediatricians is that neonatal hyperbilirubinemia is a very common finding, and complications are rare, but the condition can result in devastating life-long results, Cathy Haut, DNP, CPNP-AC, CPNP-PC, a pediatric nurse practitioner in Rehoboth Beach, Del., said in an interview.

“Previous guidelines published in 2004 and updated in 2009 included evidence-based recommendations, but additional research was still needed to provide guidance for providers to prevent complications of hyperbilirubinemia,” said Dr. Haut, who was not involved in producing the guidelines.

“New data documenting additional risk factors, the importance of ongoing breastfeeding support, and addressing hyperbilirubinemia as an urgent problem” are additions to prevention methods in the latest published guidelines, she said.

“Acute encephalopathy and kernicterus can result from hyperbilirubinemia with severe and devastating neurologic effects, but are preventable by early identification and treatment,” said Dr. Haut. Therefore, “it is not surprising that the AAP utilized continuing and more recent evidence to support new recommendations. Both maternal and neonatal risk factors have long been considered in the development of neonatal hyperbilirubinemia, but recent recommendations incorporate additional risk factor evaluation and urgency in time to appropriate care. Detailed thresholds for phototherapy and exchange transfusion will benefit the families of full-term infants without other risk factors and escalate care for those neonates with risk factors.”

However, potential barriers to following the guidelines persist, Dr. Haut noted.

“Frequent infant follow-up can be challenging for busy primary care offices with outpatient laboratory results often taking much longer to obtain than in a hospital setting,” she said.

Also, “taking a newborn to the emergency department or an inpatient laboratory can be frightening for families with the risk of illness exposure. Frequent monitoring of serum bilirubin levels is disturbing for parents and inconvenient immediately postpartum,” Dr. Haut explained. “Few practices utilize transcutaneous bilirubin monitoring which may be one method of added screening.”

In addition, “despite the importance of breastfeeding, ongoing support is not readily available for mothers after hospital discharge. A lactation specialist in the office setting can take the burden off providers and add opportunity for family education.”

As for additional research, “continued evaluation of the comparison of transcutaneous bilirubin monitoring and serum levels along with the use of transcutaneous monitoring in facilities outside the hospital setting may be warranted,” Dr. Haut said. “Data collection on incidence and accompanying risk factors of neonates who develop acute hyperbilirubinemia encephalopathy and kernicterus is a long-term study opportunity.”

The guidelines received no external funding. Lead author Dr. Kemper had no financial conflicts to disclose. Dr. Haut had no financial conflicts to disclose and serves on the editorial advisory board of Pediatric News.

Raising phototherapy thresholds and revising risk assessment are among the key changes in the American Academy of Pediatrics’ updated guidelines for managing hyperbilirubinemia in infants 35 weeks’ gestation and older.

“More than 80% of newborn infants will have some degree of jaundice,” Alex R. Kemper, MD, of Nationwide Children’s Hospital, Columbus, Ohio, and coauthors wrote. Careful monitoring is needed manage high bilirubin concentrations and avoid acute bilirubin encephalopathy (ABE) and kernicterus, a disabling neurologic condition.

The current revision, published in Pediatrics, updates and replaces the 2004 AAP clinical practice guidelines for the management and prevention of hyperbilirubinemia in newborns of at least 35 weeks’ gestation.

The guideline committee reviewed evidence published since the previous guidelines were issued in 2004, and addressed similar issues of prevention, risk assessment, monitoring, and treatment.

A notable change from 2004 was the inclusion of a 2009 recommendation update for “universal predischarge bilirubin screening with measures of total serum bilirubin (TSB) or transcutaneous bilirubin (TcB) linked to specific recommendations for follow-up,” the authors wrote.

In terms of prevention, recommendations include a direct antiglobulin test (DAT) for infants whose mother’s antibody screen was positive or unknown. In addition, exclusive breastfeeding is known to be associated with hyperbilirubinemia, but clinicians should support breastfeeding while monitoring for signs of hyperbilirubinemia because of suboptimal feeding, the authors noted. However, the guidelines recommend against oral supplementation with water or dextrose water to prevent hyperbilirubinemia.

For assessment and monitoring, the guidelines advise the use of total serum bilirubin (TSB) as the definitive test for hyperbilirubinemia to guide phototherapy and escalation of care, including exchange transfusion. “The presence of hyperbilirubinemia neurotoxicity risk factors lowers the threshold for treatment with phototherapy and the level at which care should be escalated,” the authors wrote. They also emphasized the need to consider glucose-6-phosphate dehydrogenase deficiency, a genetic condition that decreases protection against oxidative stress and has been identified as a leading cause of hazardous hyperbilirubinemia worldwide.

The guidelines recommend assessing all infants for jaundice at least every 12 hours after delivery until discharge, with TSB or TcB measured as soon as possible for those with suspected jaundice. The complete guidelines include charts for TSB levels to guide escalation of care. “Blood for TSB can be obtained at the time it is collected for newborn screening tests to avoid an additional heel stick,” the authors noted.

The rate of increase in TSB or TcB, if more than one measure is available, may identify infants at higher risk of hyperbilirubinemia, according to the guidelines, and a possible delay of hospital discharge may be needed for infants if appropriate follow-up is not feasible.

In terms of treatment, new evidence that bilirubin neurotoxicity does not occur until concentrations well above those given in the 2004 guidelines justified raising the treatment thresholds, although by a narrow range. “With the increased phototherapy thresholds, appropriately following the current guidelines including bilirubin screening during the birth hospitalization and timely postdischarge follow-up is important,” the authors wrote. The new thresholds, outlined in the complete guidelines, are based on gestational age, hyperbilirubinemia neurotoxicity risk factors, and the age of the infant in hours. However, infants may be treated at lower levels, based on individual circumstances, family preferences, and shared decision-making with clinicians. Home-based phototherapy may be used in some infants, but should not be used if there is a question about the device quality, delivery time, and ability of caregivers to use the device correctly.

“Discontinuing phototherapy is an option when the TSB has decreased by at least 2 mg/dL below the hour-specific threshold at the initiation of phototherapy,” and follow-up should be based on risk of rebound hyperbilirubinemia, according to the guidelines.

“This clinical practice guideline provides indications and approaches for phototherapy and escalation of care and when treatment and monitoring can be safely discontinued,” However, clinicians should understand the rationale for the recommendations and combine them with their clinical judgment, including shared decision-making when appropriate, the authors concluded.
 

Updated evidence supports escalating care

The take-home message for pediatricians is that neonatal hyperbilirubinemia is a very common finding, and complications are rare, but the condition can result in devastating life-long results, Cathy Haut, DNP, CPNP-AC, CPNP-PC, a pediatric nurse practitioner in Rehoboth Beach, Del., said in an interview.

“Previous guidelines published in 2004 and updated in 2009 included evidence-based recommendations, but additional research was still needed to provide guidance for providers to prevent complications of hyperbilirubinemia,” said Dr. Haut, who was not involved in producing the guidelines.

“New data documenting additional risk factors, the importance of ongoing breastfeeding support, and addressing hyperbilirubinemia as an urgent problem” are additions to prevention methods in the latest published guidelines, she said.

“Acute encephalopathy and kernicterus can result from hyperbilirubinemia with severe and devastating neurologic effects, but are preventable by early identification and treatment,” said Dr. Haut. Therefore, “it is not surprising that the AAP utilized continuing and more recent evidence to support new recommendations. Both maternal and neonatal risk factors have long been considered in the development of neonatal hyperbilirubinemia, but recent recommendations incorporate additional risk factor evaluation and urgency in time to appropriate care. Detailed thresholds for phototherapy and exchange transfusion will benefit the families of full-term infants without other risk factors and escalate care for those neonates with risk factors.”

However, potential barriers to following the guidelines persist, Dr. Haut noted.

“Frequent infant follow-up can be challenging for busy primary care offices with outpatient laboratory results often taking much longer to obtain than in a hospital setting,” she said.

Also, “taking a newborn to the emergency department or an inpatient laboratory can be frightening for families with the risk of illness exposure. Frequent monitoring of serum bilirubin levels is disturbing for parents and inconvenient immediately postpartum,” Dr. Haut explained. “Few practices utilize transcutaneous bilirubin monitoring which may be one method of added screening.”

In addition, “despite the importance of breastfeeding, ongoing support is not readily available for mothers after hospital discharge. A lactation specialist in the office setting can take the burden off providers and add opportunity for family education.”

As for additional research, “continued evaluation of the comparison of transcutaneous bilirubin monitoring and serum levels along with the use of transcutaneous monitoring in facilities outside the hospital setting may be warranted,” Dr. Haut said. “Data collection on incidence and accompanying risk factors of neonates who develop acute hyperbilirubinemia encephalopathy and kernicterus is a long-term study opportunity.”

The guidelines received no external funding. Lead author Dr. Kemper had no financial conflicts to disclose. Dr. Haut had no financial conflicts to disclose and serves on the editorial advisory board of Pediatric News.

Raising phototherapy thresholds and revising risk assessment are among the key changes in the American Academy of Pediatrics’ updated guidelines for managing hyperbilirubinemia in infants 35 weeks’ gestation and older.

“More than 80% of newborn infants will have some degree of jaundice,” Alex R. Kemper, MD, of Nationwide Children’s Hospital, Columbus, Ohio, and coauthors wrote. Careful monitoring is needed manage high bilirubin concentrations and avoid acute bilirubin encephalopathy (ABE) and kernicterus, a disabling neurologic condition.

The current revision, published in Pediatrics, updates and replaces the 2004 AAP clinical practice guidelines for the management and prevention of hyperbilirubinemia in newborns of at least 35 weeks’ gestation.

The guideline committee reviewed evidence published since the previous guidelines were issued in 2004, and addressed similar issues of prevention, risk assessment, monitoring, and treatment.

A notable change from 2004 was the inclusion of a 2009 recommendation update for “universal predischarge bilirubin screening with measures of total serum bilirubin (TSB) or transcutaneous bilirubin (TcB) linked to specific recommendations for follow-up,” the authors wrote.

In terms of prevention, recommendations include a direct antiglobulin test (DAT) for infants whose mother’s antibody screen was positive or unknown. In addition, exclusive breastfeeding is known to be associated with hyperbilirubinemia, but clinicians should support breastfeeding while monitoring for signs of hyperbilirubinemia because of suboptimal feeding, the authors noted. However, the guidelines recommend against oral supplementation with water or dextrose water to prevent hyperbilirubinemia.

For assessment and monitoring, the guidelines advise the use of total serum bilirubin (TSB) as the definitive test for hyperbilirubinemia to guide phototherapy and escalation of care, including exchange transfusion. “The presence of hyperbilirubinemia neurotoxicity risk factors lowers the threshold for treatment with phototherapy and the level at which care should be escalated,” the authors wrote. They also emphasized the need to consider glucose-6-phosphate dehydrogenase deficiency, a genetic condition that decreases protection against oxidative stress and has been identified as a leading cause of hazardous hyperbilirubinemia worldwide.

The guidelines recommend assessing all infants for jaundice at least every 12 hours after delivery until discharge, with TSB or TcB measured as soon as possible for those with suspected jaundice. The complete guidelines include charts for TSB levels to guide escalation of care. “Blood for TSB can be obtained at the time it is collected for newborn screening tests to avoid an additional heel stick,” the authors noted.

The rate of increase in TSB or TcB, if more than one measure is available, may identify infants at higher risk of hyperbilirubinemia, according to the guidelines, and a possible delay of hospital discharge may be needed for infants if appropriate follow-up is not feasible.

In terms of treatment, new evidence that bilirubin neurotoxicity does not occur until concentrations well above those given in the 2004 guidelines justified raising the treatment thresholds, although by a narrow range. “With the increased phototherapy thresholds, appropriately following the current guidelines including bilirubin screening during the birth hospitalization and timely postdischarge follow-up is important,” the authors wrote. The new thresholds, outlined in the complete guidelines, are based on gestational age, hyperbilirubinemia neurotoxicity risk factors, and the age of the infant in hours. However, infants may be treated at lower levels, based on individual circumstances, family preferences, and shared decision-making with clinicians. Home-based phototherapy may be used in some infants, but should not be used if there is a question about the device quality, delivery time, and ability of caregivers to use the device correctly.

“Discontinuing phototherapy is an option when the TSB has decreased by at least 2 mg/dL below the hour-specific threshold at the initiation of phototherapy,” and follow-up should be based on risk of rebound hyperbilirubinemia, according to the guidelines.

“This clinical practice guideline provides indications and approaches for phototherapy and escalation of care and when treatment and monitoring can be safely discontinued,” However, clinicians should understand the rationale for the recommendations and combine them with their clinical judgment, including shared decision-making when appropriate, the authors concluded.
 

Updated evidence supports escalating care

The take-home message for pediatricians is that neonatal hyperbilirubinemia is a very common finding, and complications are rare, but the condition can result in devastating life-long results, Cathy Haut, DNP, CPNP-AC, CPNP-PC, a pediatric nurse practitioner in Rehoboth Beach, Del., said in an interview.

“Previous guidelines published in 2004 and updated in 2009 included evidence-based recommendations, but additional research was still needed to provide guidance for providers to prevent complications of hyperbilirubinemia,” said Dr. Haut, who was not involved in producing the guidelines.

“New data documenting additional risk factors, the importance of ongoing breastfeeding support, and addressing hyperbilirubinemia as an urgent problem” are additions to prevention methods in the latest published guidelines, she said.

“Acute encephalopathy and kernicterus can result from hyperbilirubinemia with severe and devastating neurologic effects, but are preventable by early identification and treatment,” said Dr. Haut. Therefore, “it is not surprising that the AAP utilized continuing and more recent evidence to support new recommendations. Both maternal and neonatal risk factors have long been considered in the development of neonatal hyperbilirubinemia, but recent recommendations incorporate additional risk factor evaluation and urgency in time to appropriate care. Detailed thresholds for phototherapy and exchange transfusion will benefit the families of full-term infants without other risk factors and escalate care for those neonates with risk factors.”

However, potential barriers to following the guidelines persist, Dr. Haut noted.

“Frequent infant follow-up can be challenging for busy primary care offices with outpatient laboratory results often taking much longer to obtain than in a hospital setting,” she said.

Also, “taking a newborn to the emergency department or an inpatient laboratory can be frightening for families with the risk of illness exposure. Frequent monitoring of serum bilirubin levels is disturbing for parents and inconvenient immediately postpartum,” Dr. Haut explained. “Few practices utilize transcutaneous bilirubin monitoring which may be one method of added screening.”

In addition, “despite the importance of breastfeeding, ongoing support is not readily available for mothers after hospital discharge. A lactation specialist in the office setting can take the burden off providers and add opportunity for family education.”

As for additional research, “continued evaluation of the comparison of transcutaneous bilirubin monitoring and serum levels along with the use of transcutaneous monitoring in facilities outside the hospital setting may be warranted,” Dr. Haut said. “Data collection on incidence and accompanying risk factors of neonates who develop acute hyperbilirubinemia encephalopathy and kernicterus is a long-term study opportunity.”

The guidelines received no external funding. Lead author Dr. Kemper had no financial conflicts to disclose. Dr. Haut had no financial conflicts to disclose and serves on the editorial advisory board of Pediatric News.

Ongoing follow-up and lifestyle interventions are needed in lean patients with nonalcoholic fatty liver disease (NAFLD), suggests a panel of experts in a recent review.

They also urge screening for NAFLD in individuals who are older than 40 years with type 2 diabetes, even if they are not overweight.

NAFLD is a leading cause of chronic liver disease that affects more than 25% of the United States and worldwide populations, note lead author Michelle T. Long, MD, Boston Medical Center, Boston University, and colleagues.

Evidence-based approaches

The 15 best practice advice statements covered a wide range of clinical areas, first defining lean as a body mass index (BMI) less than 25 in non-Asian persons and less than 23 in Asian persons.

The authors go on to stipulate, for example, that lean individuals in the general population should not be screened for NAFLD but that screening should be considered for individuals older than 40 years with type 2 diabetes.

More broadly, they write that the condition should be considered in lean individuals with metabolic diseases, such as type 2 diabetes, dyslipidemia, and hypertension, as well as elevated values on liver biochemical tests or incidentally noted hepatic steatosis.

After other causes of liver diseases are ruled out, the authors note that clinicians should consider liver biopsy as the reference test if uncertainties remain about liver injury causes and/or liver fibrosis staging.

They also write that the NAFLD fibrosis score and Fibrosis-4 score, along with imaging techniques, may be used as alternatives to biopsy for staging and during follow-up.

The authors, who provide a diagnosis and management algorithm to aid clinicians, suggest that lean patients with NAFLD follow lifestyle interventions, such as exercise, diet modification, and avoidance of fructose- and sugar-sweetened drinks, to achieve weight loss of 3%-5%.

Vitamin E may be considered, they continue, in patients with biopsy-confirmed nonalcoholic steatohepatitis but without type 2 diabetes or cirrhosis. Additionally, oral pioglitazone may be considered in lean persons with biopsy-confirmed nonalcoholic steatohepatitis without cirrhosis.

In contrast, they write that the role of glucagonlike peptide 1 agonists and sodium-glucose cotransporter 2 inhibitors requires further investigation.

The advice also says that lean patients with NAFLD should be routinely evaluated for comorbid conditions, such as type 2 diabetes, dyslipidemia, and hypertension, and risk-stratified for hepatic fibrosis to identify those with advanced fibrosis or cirrhosis.

For lean patients with NAFLD and clinical markers compatible with liver cirrhosis, twice-yearly surveillance for hepatocellular carcinoma is also advised.

Fatty liver disease in lean people with metabolic conditions

Approached for comment, Liyun Yuan, MD, PhD, assistant professor of clinical medicine, University of Southern California, Los Angeles, said it is very important to have uniform guidelines for general practitioners and other specialties on NAFLD in lean individuals.

Dr. Yuan, who was not involved in the review, told this news organization that it is crucial to raise awareness of NAFLD, just like awareness of breast cancer screening among women of a certain age was increased, so that individuals are screened for metabolic conditions regardless of whether they have obesity or overweight.

Zobair Younossi, MD, MPH, professor of medicine, Virginia Commonwealth University, Inova Campus, Falls Church, Va., added that there is a lack of awareness that NAFLD occurs in lean individuals, especially in those who have diabetes.

He said in an interview that although it is accurate to define individuals as being lean in terms of their BMI, the best way is to look not only at BMI but also at waist circumference.

Dr. Younossi said that he and his colleagues have shown that when BMI is combined with waist circumference, the prediction of mortality risk in NAFLD is affected, such that lean individuals with an obese waist circumference have a higher risk for all-cause mortality.

Dr. Long is supported in part by the National Institute of Diabetes and Digestive and Kidney Diseases, Doris Duke Charitable Foundation, Gilead Sciences Research Scholars Award, Boston University School of Medicine Department of Medicine Career Investment Award, and Boston University Clinical Translational Science Institute. Dr. Long declares relationships with Novo Nordisk, Echosens Corporation, and Gilead Sciences. Dr. Yuan declares relationships with Genfit, Intercept, and Gilead Sciences. Dr. Younossi declares no relevant relationships.

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

*This article was updated on July 27, 2022.

Ongoing follow-up and lifestyle interventions are needed in lean patients with nonalcoholic fatty liver disease (NAFLD), suggests a panel of experts in a recent review.

They also urge screening for NAFLD in individuals who are older than 40 years with type 2 diabetes, even if they are not overweight.

NAFLD is a leading cause of chronic liver disease that affects more than 25% of the United States and worldwide populations, note lead author Michelle T. Long, MD, Boston Medical Center, Boston University, and colleagues.

Evidence-based approaches

The 15 best practice advice statements covered a wide range of clinical areas, first defining lean as a body mass index (BMI) less than 25 in non-Asian persons and less than 23 in Asian persons.

The authors go on to stipulate, for example, that lean individuals in the general population should not be screened for NAFLD but that screening should be considered for individuals older than 40 years with type 2 diabetes.

More broadly, they write that the condition should be considered in lean individuals with metabolic diseases, such as type 2 diabetes, dyslipidemia, and hypertension, as well as elevated values on liver biochemical tests or incidentally noted hepatic steatosis.

After other causes of liver diseases are ruled out, the authors note that clinicians should consider liver biopsy as the reference test if uncertainties remain about liver injury causes and/or liver fibrosis staging.

They also write that the NAFLD fibrosis score and Fibrosis-4 score, along with imaging techniques, may be used as alternatives to biopsy for staging and during follow-up.

The authors, who provide a diagnosis and management algorithm to aid clinicians, suggest that lean patients with NAFLD follow lifestyle interventions, such as exercise, diet modification, and avoidance of fructose- and sugar-sweetened drinks, to achieve weight loss of 3%-5%.

Vitamin E may be considered, they continue, in patients with biopsy-confirmed nonalcoholic steatohepatitis but without type 2 diabetes or cirrhosis. Additionally, oral pioglitazone may be considered in lean persons with biopsy-confirmed nonalcoholic steatohepatitis without cirrhosis.

In contrast, they write that the role of glucagonlike peptide 1 agonists and sodium-glucose cotransporter 2 inhibitors requires further investigation.

The advice also says that lean patients with NAFLD should be routinely evaluated for comorbid conditions, such as type 2 diabetes, dyslipidemia, and hypertension, and risk-stratified for hepatic fibrosis to identify those with advanced fibrosis or cirrhosis.

For lean patients with NAFLD and clinical markers compatible with liver cirrhosis, twice-yearly surveillance for hepatocellular carcinoma is also advised.

Fatty liver disease in lean people with metabolic conditions

Approached for comment, Liyun Yuan, MD, PhD, assistant professor of clinical medicine, University of Southern California, Los Angeles, said it is very important to have uniform guidelines for general practitioners and other specialties on NAFLD in lean individuals.

Dr. Yuan, who was not involved in the review, told this news organization that it is crucial to raise awareness of NAFLD, just like awareness of breast cancer screening among women of a certain age was increased, so that individuals are screened for metabolic conditions regardless of whether they have obesity or overweight.

Zobair Younossi, MD, MPH, professor of medicine, Virginia Commonwealth University, Inova Campus, Falls Church, Va., added that there is a lack of awareness that NAFLD occurs in lean individuals, especially in those who have diabetes.

He said in an interview that although it is accurate to define individuals as being lean in terms of their BMI, the best way is to look not only at BMI but also at waist circumference.

Dr. Younossi said that he and his colleagues have shown that when BMI is combined with waist circumference, the prediction of mortality risk in NAFLD is affected, such that lean individuals with an obese waist circumference have a higher risk for all-cause mortality.

Dr. Long is supported in part by the National Institute of Diabetes and Digestive and Kidney Diseases, Doris Duke Charitable Foundation, Gilead Sciences Research Scholars Award, Boston University School of Medicine Department of Medicine Career Investment Award, and Boston University Clinical Translational Science Institute. Dr. Long declares relationships with Novo Nordisk, Echosens Corporation, and Gilead Sciences. Dr. Yuan declares relationships with Genfit, Intercept, and Gilead Sciences. Dr. Younossi declares no relevant relationships.

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

*This article was updated on July 27, 2022.

Ongoing follow-up and lifestyle interventions are needed in lean patients with nonalcoholic fatty liver disease (NAFLD), suggests a panel of experts in a recent review.

They also urge screening for NAFLD in individuals who are older than 40 years with type 2 diabetes, even if they are not overweight.

NAFLD is a leading cause of chronic liver disease that affects more than 25% of the United States and worldwide populations, note lead author Michelle T. Long, MD, Boston Medical Center, Boston University, and colleagues.

Evidence-based approaches

The 15 best practice advice statements covered a wide range of clinical areas, first defining lean as a body mass index (BMI) less than 25 in non-Asian persons and less than 23 in Asian persons.

The authors go on to stipulate, for example, that lean individuals in the general population should not be screened for NAFLD but that screening should be considered for individuals older than 40 years with type 2 diabetes.

More broadly, they write that the condition should be considered in lean individuals with metabolic diseases, such as type 2 diabetes, dyslipidemia, and hypertension, as well as elevated values on liver biochemical tests or incidentally noted hepatic steatosis.

After other causes of liver diseases are ruled out, the authors note that clinicians should consider liver biopsy as the reference test if uncertainties remain about liver injury causes and/or liver fibrosis staging.

They also write that the NAFLD fibrosis score and Fibrosis-4 score, along with imaging techniques, may be used as alternatives to biopsy for staging and during follow-up.

The authors, who provide a diagnosis and management algorithm to aid clinicians, suggest that lean patients with NAFLD follow lifestyle interventions, such as exercise, diet modification, and avoidance of fructose- and sugar-sweetened drinks, to achieve weight loss of 3%-5%.

Vitamin E may be considered, they continue, in patients with biopsy-confirmed nonalcoholic steatohepatitis but without type 2 diabetes or cirrhosis. Additionally, oral pioglitazone may be considered in lean persons with biopsy-confirmed nonalcoholic steatohepatitis without cirrhosis.

In contrast, they write that the role of glucagonlike peptide 1 agonists and sodium-glucose cotransporter 2 inhibitors requires further investigation.

The advice also says that lean patients with NAFLD should be routinely evaluated for comorbid conditions, such as type 2 diabetes, dyslipidemia, and hypertension, and risk-stratified for hepatic fibrosis to identify those with advanced fibrosis or cirrhosis.

For lean patients with NAFLD and clinical markers compatible with liver cirrhosis, twice-yearly surveillance for hepatocellular carcinoma is also advised.

Fatty liver disease in lean people with metabolic conditions

Approached for comment, Liyun Yuan, MD, PhD, assistant professor of clinical medicine, University of Southern California, Los Angeles, said it is very important to have uniform guidelines for general practitioners and other specialties on NAFLD in lean individuals.

Dr. Yuan, who was not involved in the review, told this news organization that it is crucial to raise awareness of NAFLD, just like awareness of breast cancer screening among women of a certain age was increased, so that individuals are screened for metabolic conditions regardless of whether they have obesity or overweight.

Zobair Younossi, MD, MPH, professor of medicine, Virginia Commonwealth University, Inova Campus, Falls Church, Va., added that there is a lack of awareness that NAFLD occurs in lean individuals, especially in those who have diabetes.

He said in an interview that although it is accurate to define individuals as being lean in terms of their BMI, the best way is to look not only at BMI but also at waist circumference.

Dr. Younossi said that he and his colleagues have shown that when BMI is combined with waist circumference, the prediction of mortality risk in NAFLD is affected, such that lean individuals with an obese waist circumference have a higher risk for all-cause mortality.

Dr. Long is supported in part by the National Institute of Diabetes and Digestive and Kidney Diseases, Doris Duke Charitable Foundation, Gilead Sciences Research Scholars Award, Boston University School of Medicine Department of Medicine Career Investment Award, and Boston University Clinical Translational Science Institute. Dr. Long declares relationships with Novo Nordisk, Echosens Corporation, and Gilead Sciences. Dr. Yuan declares relationships with Genfit, Intercept, and Gilead Sciences. Dr. Younossi declares no relevant relationships.

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

*This article was updated on July 27, 2022.

A new clinical practice update from the American Gastroenterological Association offers practical advice around surveillance and use of new screening technologies for Barrett’s esophagus.

The AGA clinical practice update, published in Clinical Gastroenterology and Hepatology comes from the AGA’s Center for GI Innovation and Technology. It offers 15 best practice advice statements based on expert review of existing literature combined with discussion and expert opinion. The aim is “to provide an update on advances and innovation” but not to replace current guidelines.

“Guidelines operate on rigorous methodology which requires the use of [Grading of Recommendations, Assessment, Development and Evaluation] methodology and a higher level of evidence. In gastroenterology especially, innovation is moving quickly and there’s no way for patients to reap their benefits if clinical practice was dictated by guidelines alone. That said, we do need documents that support and drive innovation in clinical practice,” corresponding author Srinadh Komanduri, MD, professor of medicine and surgery in the division of gastroenterology and hepatology at Northwestern University, Chicago, told this news publication.

Asked to comment, Vivek Kaul, MD, the Segal-Watson Professor of Medicine in the Center for Advanced Therapeutic Endoscopy in the division of gastroenterology and hepatology at the University of Rochester (N.Y.) Medical Center, said that the document is “an important attempt to not only present the available scientific literature in a very concise and understandable manner, but it goes above and beyond that in terms of diving into some novel paradigms and technologies and procedures that are either emerging or will be emerging in the near future.”
 

Improving detection by dropping GERD requirement

The first of the 15 statements may also be the most paradigm shifting: The panel suggests screening via standard upper endoscopy of people with at least three risk factors for Barrett’s esophagus and esophageal adenocarcinoma, including those who are male, are non-Hispanic White, are aged above 50 years, and have a history of smoking, chronic gastroesophageal reflux disease (GERD), obesity, or a family history of Barrett’s esophagus or esophageal adenocarcinoma.

This represents a departure from all current guidelines, which stipulate GERD as a necessary prerequisite for screening. But the reason is simple, according to the authors: A majority of patients diagnosed with esophageal cancer never experience classic GERD symptoms.

“There is growing evidence in high-level publications over the last couple of years that reflux is not the ideal predictor, based on odds, for development of Barrett’s esophagus. So the consensus among the experts was that we need to remove GERD as an absolute prerequisite or we’re never going to make progress. In order to make an impact on the rise of esophageal adenocarcinoma we have to increase the denominator of patients we are seeing,” Dr. Komanduri explained.

While it might be difficult to screen every White male over 50 years of age, the data do suggest screening those who also have obesity and/or are current smokers. “That’s a perfect subset you might want to start with. There are permutations that have greater value that don’t occupy unnecessary resource utilization. Most critical are the family history of esophageal cancer or Barrett’s esophagus,” he noted.

Dr. Kaul said that a one-time Barrett’s esophagus screening of all White males over 50 years old “is not unreasonable, especially given the rising rates of esophageal cancer.”

However, he also noted, “The feasibility, preferred screening modality, incremental costs, and yield of this new strategy will need to be studied further. Access to GI endoscopy in the postpandemic world is already a concern and will need to be factored into execution of this [advice statement] and will likely impact adoption in some way.”

For his part, Dr. Komanduri said that more investigation will be needed to validate which patients most benefit from screening and that the AGA is planning educational programs for clinicians about interpreting this new paradigm.
 

New technology could make screening easier and cheaper

The availability of nonendoscopic cell collection devices, including the swallowable Cytosponge (Medtronic), EsoCheck (Lucid), and EsoCap (Capnostics) could help make screening for Barrett’s esophagus easier and more cost effective. They are designed for in-office use and don’t require sedation. Each one is currently in various stages of development and clinical trials. As of now they’re approved in the United States only for cell collection but not for Barrett’s esophagus screening, but their use is endorsed by some guidelines. The Cytosponge in particular is widely available and has been used extensively in the United Kingdom.

Dr. Kaul commented, “While there is a need for nonendoscopic screening devices, the ideal patient population and practice setting for administration of these devices has not been clearly defined. Also, who will be delivering these tests: Primary care or gastroenterology providers? These devices ... represent a major step forward and a novel paradigm for Barrett’s esophagus screening, and the only platform that non-GI providers could use.”
 

Virtual chromoendoscopy: A must have in 2022

A third best practice advice statement shouldn’t be controversial because it’s in other guidelines already, but data show clinicians aren’t always doing it: Performing screening and surveillance endoscopic examinations using virtual chromoendoscopy in addition to high-definition white light endoscopy, with adequate time spent inspecting the Barrett’s segment. The majority of data supporting this is for narrow-band imaging only.

“The blue light lets you pick up early mucosal and vascular changes which might represent dysplastic lesions. It’s not a question of should. It’s a medicolegal slam dunk; you must do it. It’s been a guideline recommendation in the last few years, and it’s just a switch on the scope. It doesn’t require separate equipment, yet people are often still skipping it,” Dr. Komanduri said.

Indeed, Dr. Kaul concurred, “The importance of a high quality, meticulous endoscopic examination for screening and surveillance in Barrett’s esophagus cannot be overemphasized.”
 

‘Finally pushing the needle in the right direction’

The overall goals, Dr. Komanduri said, are “increasing the denominator, using less invasive screening, but finding more patients. If we find more patients we’ll need to stratify their risk. We hope that all these things eventually tie together in a nice story, all with the aim of preventing an invasive cancer that can’t be treated.”

He believes the new update “is a pivotal document in this field that’s going to be a paradigm changer. A lot of aspects need further validation. It’s by no means the end. But I think we’re finally pushing the needle in the right direction as things move forward with innovation.”

Dr. Kaul agrees. “It’s highlighting the principles that may become established paradigms in the future.”

Dr. Komanduri and the other authors of the update reported relationships, including consulting and research support, with companies like Boston Scientific, Medtronic, Virgo Video Solutions, and Castle Biosciences. Dr. Kaul serves as a consultant and advisory board member for CDx Diagnostics, an advisory board member for Castle Biosciences, and an investigator for Lucid Diagnostics.

A new clinical practice update from the American Gastroenterological Association offers practical advice around surveillance and use of new screening technologies for Barrett’s esophagus.

The AGA clinical practice update, published in Clinical Gastroenterology and Hepatology comes from the AGA’s Center for GI Innovation and Technology. It offers 15 best practice advice statements based on expert review of existing literature combined with discussion and expert opinion. The aim is “to provide an update on advances and innovation” but not to replace current guidelines.

“Guidelines operate on rigorous methodology which requires the use of [Grading of Recommendations, Assessment, Development and Evaluation] methodology and a higher level of evidence. In gastroenterology especially, innovation is moving quickly and there’s no way for patients to reap their benefits if clinical practice was dictated by guidelines alone. That said, we do need documents that support and drive innovation in clinical practice,” corresponding author Srinadh Komanduri, MD, professor of medicine and surgery in the division of gastroenterology and hepatology at Northwestern University, Chicago, told this news publication.

Asked to comment, Vivek Kaul, MD, the Segal-Watson Professor of Medicine in the Center for Advanced Therapeutic Endoscopy in the division of gastroenterology and hepatology at the University of Rochester (N.Y.) Medical Center, said that the document is “an important attempt to not only present the available scientific literature in a very concise and understandable manner, but it goes above and beyond that in terms of diving into some novel paradigms and technologies and procedures that are either emerging or will be emerging in the near future.”
 

Improving detection by dropping GERD requirement

The first of the 15 statements may also be the most paradigm shifting: The panel suggests screening via standard upper endoscopy of people with at least three risk factors for Barrett’s esophagus and esophageal adenocarcinoma, including those who are male, are non-Hispanic White, are aged above 50 years, and have a history of smoking, chronic gastroesophageal reflux disease (GERD), obesity, or a family history of Barrett’s esophagus or esophageal adenocarcinoma.

This represents a departure from all current guidelines, which stipulate GERD as a necessary prerequisite for screening. But the reason is simple, according to the authors: A majority of patients diagnosed with esophageal cancer never experience classic GERD symptoms.

“There is growing evidence in high-level publications over the last couple of years that reflux is not the ideal predictor, based on odds, for development of Barrett’s esophagus. So the consensus among the experts was that we need to remove GERD as an absolute prerequisite or we’re never going to make progress. In order to make an impact on the rise of esophageal adenocarcinoma we have to increase the denominator of patients we are seeing,” Dr. Komanduri explained.

While it might be difficult to screen every White male over 50 years of age, the data do suggest screening those who also have obesity and/or are current smokers. “That’s a perfect subset you might want to start with. There are permutations that have greater value that don’t occupy unnecessary resource utilization. Most critical are the family history of esophageal cancer or Barrett’s esophagus,” he noted.

Dr. Kaul said that a one-time Barrett’s esophagus screening of all White males over 50 years old “is not unreasonable, especially given the rising rates of esophageal cancer.”

However, he also noted, “The feasibility, preferred screening modality, incremental costs, and yield of this new strategy will need to be studied further. Access to GI endoscopy in the postpandemic world is already a concern and will need to be factored into execution of this [advice statement] and will likely impact adoption in some way.”

For his part, Dr. Komanduri said that more investigation will be needed to validate which patients most benefit from screening and that the AGA is planning educational programs for clinicians about interpreting this new paradigm.
 

New technology could make screening easier and cheaper

The availability of nonendoscopic cell collection devices, including the swallowable Cytosponge (Medtronic), EsoCheck (Lucid), and EsoCap (Capnostics) could help make screening for Barrett’s esophagus easier and more cost effective. They are designed for in-office use and don’t require sedation. Each one is currently in various stages of development and clinical trials. As of now they’re approved in the United States only for cell collection but not for Barrett’s esophagus screening, but their use is endorsed by some guidelines. The Cytosponge in particular is widely available and has been used extensively in the United Kingdom.

Dr. Kaul commented, “While there is a need for nonendoscopic screening devices, the ideal patient population and practice setting for administration of these devices has not been clearly defined. Also, who will be delivering these tests: Primary care or gastroenterology providers? These devices ... represent a major step forward and a novel paradigm for Barrett’s esophagus screening, and the only platform that non-GI providers could use.”
 

Virtual chromoendoscopy: A must have in 2022

A third best practice advice statement shouldn’t be controversial because it’s in other guidelines already, but data show clinicians aren’t always doing it: Performing screening and surveillance endoscopic examinations using virtual chromoendoscopy in addition to high-definition white light endoscopy, with adequate time spent inspecting the Barrett’s segment. The majority of data supporting this is for narrow-band imaging only.

“The blue light lets you pick up early mucosal and vascular changes which might represent dysplastic lesions. It’s not a question of should. It’s a medicolegal slam dunk; you must do it. It’s been a guideline recommendation in the last few years, and it’s just a switch on the scope. It doesn’t require separate equipment, yet people are often still skipping it,” Dr. Komanduri said.

Indeed, Dr. Kaul concurred, “The importance of a high quality, meticulous endoscopic examination for screening and surveillance in Barrett’s esophagus cannot be overemphasized.”
 

‘Finally pushing the needle in the right direction’

The overall goals, Dr. Komanduri said, are “increasing the denominator, using less invasive screening, but finding more patients. If we find more patients we’ll need to stratify their risk. We hope that all these things eventually tie together in a nice story, all with the aim of preventing an invasive cancer that can’t be treated.”

He believes the new update “is a pivotal document in this field that’s going to be a paradigm changer. A lot of aspects need further validation. It’s by no means the end. But I think we’re finally pushing the needle in the right direction as things move forward with innovation.”

Dr. Kaul agrees. “It’s highlighting the principles that may become established paradigms in the future.”

Dr. Komanduri and the other authors of the update reported relationships, including consulting and research support, with companies like Boston Scientific, Medtronic, Virgo Video Solutions, and Castle Biosciences. Dr. Kaul serves as a consultant and advisory board member for CDx Diagnostics, an advisory board member for Castle Biosciences, and an investigator for Lucid Diagnostics.

A new clinical practice update from the American Gastroenterological Association offers practical advice around surveillance and use of new screening technologies for Barrett’s esophagus.

The AGA clinical practice update, published in Clinical Gastroenterology and Hepatology comes from the AGA’s Center for GI Innovation and Technology. It offers 15 best practice advice statements based on expert review of existing literature combined with discussion and expert opinion. The aim is “to provide an update on advances and innovation” but not to replace current guidelines.

“Guidelines operate on rigorous methodology which requires the use of [Grading of Recommendations, Assessment, Development and Evaluation] methodology and a higher level of evidence. In gastroenterology especially, innovation is moving quickly and there’s no way for patients to reap their benefits if clinical practice was dictated by guidelines alone. That said, we do need documents that support and drive innovation in clinical practice,” corresponding author Srinadh Komanduri, MD, professor of medicine and surgery in the division of gastroenterology and hepatology at Northwestern University, Chicago, told this news publication.

Asked to comment, Vivek Kaul, MD, the Segal-Watson Professor of Medicine in the Center for Advanced Therapeutic Endoscopy in the division of gastroenterology and hepatology at the University of Rochester (N.Y.) Medical Center, said that the document is “an important attempt to not only present the available scientific literature in a very concise and understandable manner, but it goes above and beyond that in terms of diving into some novel paradigms and technologies and procedures that are either emerging or will be emerging in the near future.”
 

Improving detection by dropping GERD requirement

The first of the 15 statements may also be the most paradigm shifting: The panel suggests screening via standard upper endoscopy of people with at least three risk factors for Barrett’s esophagus and esophageal adenocarcinoma, including those who are male, are non-Hispanic White, are aged above 50 years, and have a history of smoking, chronic gastroesophageal reflux disease (GERD), obesity, or a family history of Barrett’s esophagus or esophageal adenocarcinoma.

This represents a departure from all current guidelines, which stipulate GERD as a necessary prerequisite for screening. But the reason is simple, according to the authors: A majority of patients diagnosed with esophageal cancer never experience classic GERD symptoms.

“There is growing evidence in high-level publications over the last couple of years that reflux is not the ideal predictor, based on odds, for development of Barrett’s esophagus. So the consensus among the experts was that we need to remove GERD as an absolute prerequisite or we’re never going to make progress. In order to make an impact on the rise of esophageal adenocarcinoma we have to increase the denominator of patients we are seeing,” Dr. Komanduri explained.

While it might be difficult to screen every White male over 50 years of age, the data do suggest screening those who also have obesity and/or are current smokers. “That’s a perfect subset you might want to start with. There are permutations that have greater value that don’t occupy unnecessary resource utilization. Most critical are the family history of esophageal cancer or Barrett’s esophagus,” he noted.

Dr. Kaul said that a one-time Barrett’s esophagus screening of all White males over 50 years old “is not unreasonable, especially given the rising rates of esophageal cancer.”

However, he also noted, “The feasibility, preferred screening modality, incremental costs, and yield of this new strategy will need to be studied further. Access to GI endoscopy in the postpandemic world is already a concern and will need to be factored into execution of this [advice statement] and will likely impact adoption in some way.”

For his part, Dr. Komanduri said that more investigation will be needed to validate which patients most benefit from screening and that the AGA is planning educational programs for clinicians about interpreting this new paradigm.
 

New technology could make screening easier and cheaper

The availability of nonendoscopic cell collection devices, including the swallowable Cytosponge (Medtronic), EsoCheck (Lucid), and EsoCap (Capnostics) could help make screening for Barrett’s esophagus easier and more cost effective. They are designed for in-office use and don’t require sedation. Each one is currently in various stages of development and clinical trials. As of now they’re approved in the United States only for cell collection but not for Barrett’s esophagus screening, but their use is endorsed by some guidelines. The Cytosponge in particular is widely available and has been used extensively in the United Kingdom.

Dr. Kaul commented, “While there is a need for nonendoscopic screening devices, the ideal patient population and practice setting for administration of these devices has not been clearly defined. Also, who will be delivering these tests: Primary care or gastroenterology providers? These devices ... represent a major step forward and a novel paradigm for Barrett’s esophagus screening, and the only platform that non-GI providers could use.”
 

Virtual chromoendoscopy: A must have in 2022

A third best practice advice statement shouldn’t be controversial because it’s in other guidelines already, but data show clinicians aren’t always doing it: Performing screening and surveillance endoscopic examinations using virtual chromoendoscopy in addition to high-definition white light endoscopy, with adequate time spent inspecting the Barrett’s segment. The majority of data supporting this is for narrow-band imaging only.

“The blue light lets you pick up early mucosal and vascular changes which might represent dysplastic lesions. It’s not a question of should. It’s a medicolegal slam dunk; you must do it. It’s been a guideline recommendation in the last few years, and it’s just a switch on the scope. It doesn’t require separate equipment, yet people are often still skipping it,” Dr. Komanduri said.

Indeed, Dr. Kaul concurred, “The importance of a high quality, meticulous endoscopic examination for screening and surveillance in Barrett’s esophagus cannot be overemphasized.”
 

‘Finally pushing the needle in the right direction’

The overall goals, Dr. Komanduri said, are “increasing the denominator, using less invasive screening, but finding more patients. If we find more patients we’ll need to stratify their risk. We hope that all these things eventually tie together in a nice story, all with the aim of preventing an invasive cancer that can’t be treated.”

He believes the new update “is a pivotal document in this field that’s going to be a paradigm changer. A lot of aspects need further validation. It’s by no means the end. But I think we’re finally pushing the needle in the right direction as things move forward with innovation.”

Dr. Kaul agrees. “It’s highlighting the principles that may become established paradigms in the future.”

Dr. Komanduri and the other authors of the update reported relationships, including consulting and research support, with companies like Boston Scientific, Medtronic, Virgo Video Solutions, and Castle Biosciences. Dr. Kaul serves as a consultant and advisory board member for CDx Diagnostics, an advisory board member for Castle Biosciences, and an investigator for Lucid Diagnostics.

New risk thresholds used to guide statin therapy for primary prevention of atherosclerotic cardiovascular disease in the latest European guidelines dramatically reduce eligibility for statin use in low-risk countries, a new study has found.

The authors reported that new risk thresholds that were chosen for statin treatment in the 2021 European Society of Cardiology guidelines reduce statin eligibility to only 4% of the target population and essentially eliminate a statin indication in women.

“We have guidelines in place to try to prevent cardiovascular disease but the risk threshold in this new guideline means that almost nobody qualifies for treatment in many countries, which will lead to almost no prevention of future cardiovascular disease in those countries,” lead author Martin Bødtker Mortensen, MD, PhD, Aarhus (Denmark) University Hospital, commented in an interview.

“We argue that the risk thresholds need to be lowered to get the statin eligibility in European countries to be in line with thresholds in the U.K. and U.S., which are based on randomized, controlled trials,” he added.

The study was published online in JAMA Cardiology.

An accompanying editorial describes the results of the study as “alarming,” and, if confirmed, said the guidelines should be revisited to “prevent a step backwards in the use of statins in primary prevention.”

For the study, Dr. Mortensen and colleagues set out to compare the clinical performance of the new European prevention guidelines with American College of Cardiology/American Heart Association, United Kingdom–National Institute for Health and Care Excellence, and the 2019 European guidelines in a contemporary European cohort of 66,909 apparently healthy individuals from the Copenhagen General Population Study.

During the 9-year follow-up, a range of 2,962-4,277 nonfatal and fatal cardiovascular events was observed, as defined by the models in the various guidelines.

Results showed that although the new 2021 European guidelines introduced a new and improved risk model, known as SCORE2, the updated age-specific recommendations dramatically reduced eligibility for a class I recommendation for statin therapy to only 4% of individuals, aged 40-69 years, and less than 1% of women.

This is in sharp contrast to the previous 2019 European guidelines as well as current UK-NICE and US-ACC/AHA guidelines that provide class I/strong recommendations to 20%, 26%, and 34% of individuals, respectively, with better clinical performance in both men and women, the authors report.

The researchers also reported other analyses in which the sensitivity of the new European guidelines was improved considerably by lowering the treatment thresholds.

Dr. Mortensen explained to this news organization that the original SCORE risk model used in ESC guidelines was problematic as it only predicts the 10-year risk of fatal atherosclerotic cardiovascular events, whereas those from the United States and United Kingdom used both fatal and nonfatal cardiovascular events.

“Now the ESC has updated its model and the new model is much better in that it predicts both fatal and nonfatal events, and the predicted risk correlates well with the actual risk. So that’s a big step forward. However, the new thresholds for statin treatment are far too high for low-risk European countries because very few individuals will now qualify for statin therapy,” he said.

“The problem is that, if we use these guidelines, the vast majority of those individuals who will develop cardiovascular disease within 10 years will not be assigned statin therapy that can reduce this risk. There will be lots of individuals who are at high risk of cardiovascular disease, but these guidelines will not identify them as needing to take a statin,” Dr. Mortensen commented.

“If we use the U.K. or U.S. guidelines, far more people in these low-risk European countries would be eligible for statin therapy and we would prevent far more events than if we use the new ESC guidelines,” he added.

Dr. Mortensen explained that the problem arises from having four different risk score models in Europe for areas at different risk, but they all use the same risk thresholds for statin treatment.

“In general, Eastern European countries have higher risk than Western European countries, so these guidelines may work quite well in Eastern European countries but in low-risk Western European countries, where the low-risk score model is used, very few people will qualify for statin therapy,” he said.

While Dr. Mortensen is not against the idea of different risk models in areas that have different risks, he says this needs to be accompanied by different risk thresholds in the different risk areas.

Asked whether there is an argument that most individuals in low-risk countries may not need to take a statin, Dr. Mortensen countered: “One of the reasons the risk is low in many of these European countries is the high use of preventative medication. So, if a threshold that is too high is used most people will not take a statin anymore and the risk in these countries will increase again.”

Authors of the accompanying editorial, Ann Marie Navar, MD, PhD, University of Texas Southwestern Medical Center, Dallas; Gregg C. Fonarow, MD, University of California, Los Angeles; and Michael J. Pencina, PhD, Duke University Medical Center, Durham, N.C., agreed with Dr. Mortensen that the problems appear to arise from use of a risk score that is highly influenced by regional cardiovascular burden.

They point out that under the current guidelines, a 55-year-old woman (smoker; systolic blood pressure, 130 mm Hg; non–HDL cholesterol, 4.0 mmol/L) would have a 10-year predicted risk of having a cardiovascular event of 5% in Denmark but a predicted risk of 18% in Romania.

“While there may be regional differences in environmental risk factors, location alone should not cause a fourfold difference in an individual’s predicted cardiovascular risk,” they wrote.

The editorialists also elaborated on Dr. Mortensen’s point that the new guideline creates a system that eventually becomes a victim of its own success.

“As countries are successful in implementing statin therapy to lower CVD, CVD rates drop, and progressively fewer individuals are then eligible for the very therapy that contributed to the decline in CVD in the first place,” they noted.

The editorialists called for the analysis to be replicated in other low-risk countries and extended to higher-risk regions, with a focus on potential overtreatment of men and older adults.

“If confirmed, the present findings should be a catalyst for the ESC to revisit or augment their current guidelines to prevent a step backward in the use of statins in primary prevention,” they concluded.

This news organization asked the ESC for a response to the findings, but did not comment by press time.

This work was supported by the Lundbeck Foundation, Herlev and Gentofte Hospital, Copenhagen University Hospital, the Copenhagen County Foundation, and Aarhus University, Denmark. Dr. Mortensen reported no disclosures.

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

New risk thresholds used to guide statin therapy for primary prevention of atherosclerotic cardiovascular disease in the latest European guidelines dramatically reduce eligibility for statin use in low-risk countries, a new study has found.

The authors reported that new risk thresholds that were chosen for statin treatment in the 2021 European Society of Cardiology guidelines reduce statin eligibility to only 4% of the target population and essentially eliminate a statin indication in women.

“We have guidelines in place to try to prevent cardiovascular disease but the risk threshold in this new guideline means that almost nobody qualifies for treatment in many countries, which will lead to almost no prevention of future cardiovascular disease in those countries,” lead author Martin Bødtker Mortensen, MD, PhD, Aarhus (Denmark) University Hospital, commented in an interview.

“We argue that the risk thresholds need to be lowered to get the statin eligibility in European countries to be in line with thresholds in the U.K. and U.S., which are based on randomized, controlled trials,” he added.

The study was published online in JAMA Cardiology.

An accompanying editorial describes the results of the study as “alarming,” and, if confirmed, said the guidelines should be revisited to “prevent a step backwards in the use of statins in primary prevention.”

For the study, Dr. Mortensen and colleagues set out to compare the clinical performance of the new European prevention guidelines with American College of Cardiology/American Heart Association, United Kingdom–National Institute for Health and Care Excellence, and the 2019 European guidelines in a contemporary European cohort of 66,909 apparently healthy individuals from the Copenhagen General Population Study.

During the 9-year follow-up, a range of 2,962-4,277 nonfatal and fatal cardiovascular events was observed, as defined by the models in the various guidelines.

Results showed that although the new 2021 European guidelines introduced a new and improved risk model, known as SCORE2, the updated age-specific recommendations dramatically reduced eligibility for a class I recommendation for statin therapy to only 4% of individuals, aged 40-69 years, and less than 1% of women.

This is in sharp contrast to the previous 2019 European guidelines as well as current UK-NICE and US-ACC/AHA guidelines that provide class I/strong recommendations to 20%, 26%, and 34% of individuals, respectively, with better clinical performance in both men and women, the authors report.

The researchers also reported other analyses in which the sensitivity of the new European guidelines was improved considerably by lowering the treatment thresholds.

Dr. Mortensen explained to this news organization that the original SCORE risk model used in ESC guidelines was problematic as it only predicts the 10-year risk of fatal atherosclerotic cardiovascular events, whereas those from the United States and United Kingdom used both fatal and nonfatal cardiovascular events.

“Now the ESC has updated its model and the new model is much better in that it predicts both fatal and nonfatal events, and the predicted risk correlates well with the actual risk. So that’s a big step forward. However, the new thresholds for statin treatment are far too high for low-risk European countries because very few individuals will now qualify for statin therapy,” he said.

“The problem is that, if we use these guidelines, the vast majority of those individuals who will develop cardiovascular disease within 10 years will not be assigned statin therapy that can reduce this risk. There will be lots of individuals who are at high risk of cardiovascular disease, but these guidelines will not identify them as needing to take a statin,” Dr. Mortensen commented.

“If we use the U.K. or U.S. guidelines, far more people in these low-risk European countries would be eligible for statin therapy and we would prevent far more events than if we use the new ESC guidelines,” he added.

Dr. Mortensen explained that the problem arises from having four different risk score models in Europe for areas at different risk, but they all use the same risk thresholds for statin treatment.

“In general, Eastern European countries have higher risk than Western European countries, so these guidelines may work quite well in Eastern European countries but in low-risk Western European countries, where the low-risk score model is used, very few people will qualify for statin therapy,” he said.

While Dr. Mortensen is not against the idea of different risk models in areas that have different risks, he says this needs to be accompanied by different risk thresholds in the different risk areas.

Asked whether there is an argument that most individuals in low-risk countries may not need to take a statin, Dr. Mortensen countered: “One of the reasons the risk is low in many of these European countries is the high use of preventative medication. So, if a threshold that is too high is used most people will not take a statin anymore and the risk in these countries will increase again.”

Authors of the accompanying editorial, Ann Marie Navar, MD, PhD, University of Texas Southwestern Medical Center, Dallas; Gregg C. Fonarow, MD, University of California, Los Angeles; and Michael J. Pencina, PhD, Duke University Medical Center, Durham, N.C., agreed with Dr. Mortensen that the problems appear to arise from use of a risk score that is highly influenced by regional cardiovascular burden.

They point out that under the current guidelines, a 55-year-old woman (smoker; systolic blood pressure, 130 mm Hg; non–HDL cholesterol, 4.0 mmol/L) would have a 10-year predicted risk of having a cardiovascular event of 5% in Denmark but a predicted risk of 18% in Romania.

“While there may be regional differences in environmental risk factors, location alone should not cause a fourfold difference in an individual’s predicted cardiovascular risk,” they wrote.

The editorialists also elaborated on Dr. Mortensen’s point that the new guideline creates a system that eventually becomes a victim of its own success.

“As countries are successful in implementing statin therapy to lower CVD, CVD rates drop, and progressively fewer individuals are then eligible for the very therapy that contributed to the decline in CVD in the first place,” they noted.

The editorialists called for the analysis to be replicated in other low-risk countries and extended to higher-risk regions, with a focus on potential overtreatment of men and older adults.

“If confirmed, the present findings should be a catalyst for the ESC to revisit or augment their current guidelines to prevent a step backward in the use of statins in primary prevention,” they concluded.

This news organization asked the ESC for a response to the findings, but did not comment by press time.

This work was supported by the Lundbeck Foundation, Herlev and Gentofte Hospital, Copenhagen University Hospital, the Copenhagen County Foundation, and Aarhus University, Denmark. Dr. Mortensen reported no disclosures.

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

New risk thresholds used to guide statin therapy for primary prevention of atherosclerotic cardiovascular disease in the latest European guidelines dramatically reduce eligibility for statin use in low-risk countries, a new study has found.

The authors reported that new risk thresholds that were chosen for statin treatment in the 2021 European Society of Cardiology guidelines reduce statin eligibility to only 4% of the target population and essentially eliminate a statin indication in women.

“We have guidelines in place to try to prevent cardiovascular disease but the risk threshold in this new guideline means that almost nobody qualifies for treatment in many countries, which will lead to almost no prevention of future cardiovascular disease in those countries,” lead author Martin Bødtker Mortensen, MD, PhD, Aarhus (Denmark) University Hospital, commented in an interview.

“We argue that the risk thresholds need to be lowered to get the statin eligibility in European countries to be in line with thresholds in the U.K. and U.S., which are based on randomized, controlled trials,” he added.

The study was published online in JAMA Cardiology.

An accompanying editorial describes the results of the study as “alarming,” and, if confirmed, said the guidelines should be revisited to “prevent a step backwards in the use of statins in primary prevention.”

For the study, Dr. Mortensen and colleagues set out to compare the clinical performance of the new European prevention guidelines with American College of Cardiology/American Heart Association, United Kingdom–National Institute for Health and Care Excellence, and the 2019 European guidelines in a contemporary European cohort of 66,909 apparently healthy individuals from the Copenhagen General Population Study.

During the 9-year follow-up, a range of 2,962-4,277 nonfatal and fatal cardiovascular events was observed, as defined by the models in the various guidelines.

Results showed that although the new 2021 European guidelines introduced a new and improved risk model, known as SCORE2, the updated age-specific recommendations dramatically reduced eligibility for a class I recommendation for statin therapy to only 4% of individuals, aged 40-69 years, and less than 1% of women.

This is in sharp contrast to the previous 2019 European guidelines as well as current UK-NICE and US-ACC/AHA guidelines that provide class I/strong recommendations to 20%, 26%, and 34% of individuals, respectively, with better clinical performance in both men and women, the authors report.

The researchers also reported other analyses in which the sensitivity of the new European guidelines was improved considerably by lowering the treatment thresholds.

Dr. Mortensen explained to this news organization that the original SCORE risk model used in ESC guidelines was problematic as it only predicts the 10-year risk of fatal atherosclerotic cardiovascular events, whereas those from the United States and United Kingdom used both fatal and nonfatal cardiovascular events.

“Now the ESC has updated its model and the new model is much better in that it predicts both fatal and nonfatal events, and the predicted risk correlates well with the actual risk. So that’s a big step forward. However, the new thresholds for statin treatment are far too high for low-risk European countries because very few individuals will now qualify for statin therapy,” he said.

“The problem is that, if we use these guidelines, the vast majority of those individuals who will develop cardiovascular disease within 10 years will not be assigned statin therapy that can reduce this risk. There will be lots of individuals who are at high risk of cardiovascular disease, but these guidelines will not identify them as needing to take a statin,” Dr. Mortensen commented.

“If we use the U.K. or U.S. guidelines, far more people in these low-risk European countries would be eligible for statin therapy and we would prevent far more events than if we use the new ESC guidelines,” he added.

Dr. Mortensen explained that the problem arises from having four different risk score models in Europe for areas at different risk, but they all use the same risk thresholds for statin treatment.

“In general, Eastern European countries have higher risk than Western European countries, so these guidelines may work quite well in Eastern European countries but in low-risk Western European countries, where the low-risk score model is used, very few people will qualify for statin therapy,” he said.

While Dr. Mortensen is not against the idea of different risk models in areas that have different risks, he says this needs to be accompanied by different risk thresholds in the different risk areas.

Asked whether there is an argument that most individuals in low-risk countries may not need to take a statin, Dr. Mortensen countered: “One of the reasons the risk is low in many of these European countries is the high use of preventative medication. So, if a threshold that is too high is used most people will not take a statin anymore and the risk in these countries will increase again.”

Authors of the accompanying editorial, Ann Marie Navar, MD, PhD, University of Texas Southwestern Medical Center, Dallas; Gregg C. Fonarow, MD, University of California, Los Angeles; and Michael J. Pencina, PhD, Duke University Medical Center, Durham, N.C., agreed with Dr. Mortensen that the problems appear to arise from use of a risk score that is highly influenced by regional cardiovascular burden.

They point out that under the current guidelines, a 55-year-old woman (smoker; systolic blood pressure, 130 mm Hg; non–HDL cholesterol, 4.0 mmol/L) would have a 10-year predicted risk of having a cardiovascular event of 5% in Denmark but a predicted risk of 18% in Romania.

“While there may be regional differences in environmental risk factors, location alone should not cause a fourfold difference in an individual’s predicted cardiovascular risk,” they wrote.

The editorialists also elaborated on Dr. Mortensen’s point that the new guideline creates a system that eventually becomes a victim of its own success.

“As countries are successful in implementing statin therapy to lower CVD, CVD rates drop, and progressively fewer individuals are then eligible for the very therapy that contributed to the decline in CVD in the first place,” they noted.

The editorialists called for the analysis to be replicated in other low-risk countries and extended to higher-risk regions, with a focus on potential overtreatment of men and older adults.

“If confirmed, the present findings should be a catalyst for the ESC to revisit or augment their current guidelines to prevent a step backward in the use of statins in primary prevention,” they concluded.

This news organization asked the ESC for a response to the findings, but did not comment by press time.

This work was supported by the Lundbeck Foundation, Herlev and Gentofte Hospital, Copenhagen University Hospital, the Copenhagen County Foundation, and Aarhus University, Denmark. Dr. Mortensen reported no disclosures.

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

About 80% of American adults have low to moderate cardiovascular (CV) health based on the American Heart Association checklist for optimal heart health, which now includes healthy sleep as an essential component for heart health.

With the addition of sleep, “Life’s Essential 8” replaces the AHA’s “Life’s Simple 7” checklist.

“The new metric of sleep duration reflects the latest research findings: Sleep impacts overall health, and people who have healthier sleep patterns manage health factors such as weight, blood pressure, or risk for type 2 diabetes more effectively,” AHA President Donald M. Lloyd-Jones, MD, said in a news release.

“In addition, advances in ways to measure sleep, such as with wearable devices, now offer people the ability to reliably and routinely monitor their sleep habits at home,” said Dr. Lloyd-Jones, chair of the department of preventive medicine at Northwestern University in Chicago.

The AHA Presidential Advisory – Life’s Essential 8: Updating and Enhancing the American Heart Association’s Construct on Cardiovascular Health – was published online in the journal Circulation.

A companion paper published simultaneously in Circulation reports the first study using Life’s Essential 8.

Overall, the results show that CV health of the U.S. population is “suboptimal, and we see important differences across age and sociodemographic groups,” Dr. Lloyd-Jones said.
 

Refining Life’s Simple 7

The AHA first defined the seven metrics for optimal CV health in 2010. After 12 years and more than 2,400 scientific papers on the topic, new discoveries in CV health and ways to measure it provided an opportunity to revisit each health component in more detail and provide updates as needed, the AHA explains.

“We felt it was the right time to conduct a comprehensive review of the latest research to refine the existing metrics and consider any new metrics that add value to assessing cardiovascular health for all people,” Dr. Lloyd-Jones said.

Four of the original metrics have been redefined for consistency with newer clinical guidelines or compatibility with new measurement tools, and the scoring system can now also be applied to anyone ages 2 and older. Here is a snapshot of Life’s Essential 8 metrics, including updates.

1. Diet (updated) 

The tool includes a new guide to assess diet quality for adults and children at the individual and population level. At the population level, dietary assessment is based on daily intake of elements in the Dietary Approaches to Stop Hypertension (DASH) eating pattern. For individuals, the Mediterranean Eating Pattern for Americans (MEPA) is used to assess and monitor cardiovascular health.

2. Physical activity (no changes)

Physical activity continues to be measured by the total number of minutes of moderate or vigorous physical activity per week, as defined by the U.S. Physical Activity Guidelines for Americans (2nd edition). The optimal level is 150 minutes (2.5 hours) of moderate physical activity or more per week or 75 minutes per week of vigorous-intensity physical activity for adults; 420 minutes (7 hours) or more per week for children ages 6 and older; and age-specific modifications for younger children.

3. Nicotine exposure (updated)

Use of inhaled nicotine-delivery systems, which includes e-cigarettes or vaping devices, has been added since the previous metric monitored only traditional, combustible cigarettes. This reflects use by adults and youth and their implications on long-term health. Second-hand smoke exposure for children and adults has also been added.

4. Sleep duration (new)

Sleep duration is associated with CV health. Measured by average hours of sleep per night, the ideal level is 7-9 hours daily for adults. Ideal daily sleep ranges for children are 10-16 hours per 24 hours for ages 5 and younger; 9-12 hours for ages 6-12 years; and 8-10 hours for ages 13-18 years.

5. Body mass index (no changes)

The AHA acknowledges that body mass index (BMI) is an imperfect metric. Yet, because it’s easily calculated and widely available, BMI continues as a “reasonable” gauge to assess weight categories that may lead to health problems. BMI of 18.5-24.9 is associated with the highest levels of CV health. The AHA notes that BMI ranges and the subsequent health risks associated with them may differ among people from diverse racial or ethnic backgrounds or ancestry. This aligns with the World Health Organization recommendations to adjust BMI ranges for people of Asian or Pacific Islander ancestry because recent evidence indicates their risk of conditions such as CVD or type 2 diabetes is higher at a lower BMI.

6. Blood lipids (updated)

The metric for blood lipids (cholesterol and triglycerides) is updated to use non-HDL cholesterol as the preferred number to monitor, rather than total cholesterol. This shift is made because non-HDL cholesterol can be measured without fasting beforehand (thereby increasing its availability at any time of day and implementation at more appointments) and reliably calculated among all people.

7. Blood glucose (updated)

This metric is expanded to include the option of hemoglobin A1c readings or blood glucose levels for people with or without type 1 or 2 diabetes or prediabetes.

8. Blood pressure (no changes)

Blood pressure criteria remain unchanged from 2017 guidance that established levels less than 120/80 mm Hg as optimal, and defined hypertension as 130-139 mm Hg systolic pressure or 80-89 mm Hg diastolic pressure.

‘Concerning’ new data

Results of the first study using Life’s Essential 8 show that the overall CV health of the U.S. population is “well below ideal,” with 80% of adults scoring at a low or moderate level, the researchers report.

Data for the analysis came from 2013-2018 U.S. National Health and Nutrition Examination surveys (NHANES) of more than 13,500 adults aged 20-79 years and nearly 9,900 children aged 2-19 years. Among the key findings:

• The average CV health score based on Life’s Essential 8 was 64.7 for adults and 65.5 for children – in the moderate range on the 0-100 scale.
• Only 0.45% of adults had a perfect score of 100; 20% had high CV health (score of 80 or higher), 63% moderate (score of 50-79), and 18% had low CV health (score of less than 50).
• Adult women had higher average CV health scores (67) compared with men (62.5).
• In general, adults scored lowest in the areas of diet, physical activity, and BMI.
• CV health scores were generally lower at older ages.
• Non-Hispanic Asian Americans had a higher average CV health score than other racial/ethnic groups. Non-Hispanic Whites had the second highest average CV health score, followed, in order, by Hispanic (other than Mexican), Mexican, and non-Hispanic Blacks.
• Children’s diet scores were low, at an average of 40.6.
• Adult sociodemographic groups varied notably in CV health scores for diet, nicotine exposure, blood glucose, and blood pressure.

“These data represent the first look at the cardiovascular health of the U.S. population using the AHA’s new Life’s Essential 8 scoring algorithm,” Dr. Lloyd-Jones said.

“Life’s Essential 8 is a major step forward in our ability to identify when cardiovascular health can be preserved and when it is suboptimal. It should energize efforts to improve cardiovascular health for all people and at every life stage,” Dr. Lloyd-Jones added.

“Analyses like this can help policymakers, communities, clinicians, and the public to understand the opportunities to intervene to improve and maintain optimal cardiovascular health across the life course,” he said.

This research had no commercial funding. The authors have no reported no relevant financial relationships.

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

About 80% of American adults have low to moderate cardiovascular (CV) health based on the American Heart Association checklist for optimal heart health, which now includes healthy sleep as an essential component for heart health.

With the addition of sleep, “Life’s Essential 8” replaces the AHA’s “Life’s Simple 7” checklist.

“The new metric of sleep duration reflects the latest research findings: Sleep impacts overall health, and people who have healthier sleep patterns manage health factors such as weight, blood pressure, or risk for type 2 diabetes more effectively,” AHA President Donald M. Lloyd-Jones, MD, said in a news release.

“In addition, advances in ways to measure sleep, such as with wearable devices, now offer people the ability to reliably and routinely monitor their sleep habits at home,” said Dr. Lloyd-Jones, chair of the department of preventive medicine at Northwestern University in Chicago.

The AHA Presidential Advisory – Life’s Essential 8: Updating and Enhancing the American Heart Association’s Construct on Cardiovascular Health – was published online in the journal Circulation.

A companion paper published simultaneously in Circulation reports the first study using Life’s Essential 8.

Overall, the results show that CV health of the U.S. population is “suboptimal, and we see important differences across age and sociodemographic groups,” Dr. Lloyd-Jones said.
 

Refining Life’s Simple 7

The AHA first defined the seven metrics for optimal CV health in 2010. After 12 years and more than 2,400 scientific papers on the topic, new discoveries in CV health and ways to measure it provided an opportunity to revisit each health component in more detail and provide updates as needed, the AHA explains.

“We felt it was the right time to conduct a comprehensive review of the latest research to refine the existing metrics and consider any new metrics that add value to assessing cardiovascular health for all people,” Dr. Lloyd-Jones said.

Four of the original metrics have been redefined for consistency with newer clinical guidelines or compatibility with new measurement tools, and the scoring system can now also be applied to anyone ages 2 and older. Here is a snapshot of Life’s Essential 8 metrics, including updates.

1. Diet (updated) 

The tool includes a new guide to assess diet quality for adults and children at the individual and population level. At the population level, dietary assessment is based on daily intake of elements in the Dietary Approaches to Stop Hypertension (DASH) eating pattern. For individuals, the Mediterranean Eating Pattern for Americans (MEPA) is used to assess and monitor cardiovascular health.

2. Physical activity (no changes)

Physical activity continues to be measured by the total number of minutes of moderate or vigorous physical activity per week, as defined by the U.S. Physical Activity Guidelines for Americans (2nd edition). The optimal level is 150 minutes (2.5 hours) of moderate physical activity or more per week or 75 minutes per week of vigorous-intensity physical activity for adults; 420 minutes (7 hours) or more per week for children ages 6 and older; and age-specific modifications for younger children.

3. Nicotine exposure (updated)

Use of inhaled nicotine-delivery systems, which includes e-cigarettes or vaping devices, has been added since the previous metric monitored only traditional, combustible cigarettes. This reflects use by adults and youth and their implications on long-term health. Second-hand smoke exposure for children and adults has also been added.

4. Sleep duration (new)

Sleep duration is associated with CV health. Measured by average hours of sleep per night, the ideal level is 7-9 hours daily for adults. Ideal daily sleep ranges for children are 10-16 hours per 24 hours for ages 5 and younger; 9-12 hours for ages 6-12 years; and 8-10 hours for ages 13-18 years.

5. Body mass index (no changes)

The AHA acknowledges that body mass index (BMI) is an imperfect metric. Yet, because it’s easily calculated and widely available, BMI continues as a “reasonable” gauge to assess weight categories that may lead to health problems. BMI of 18.5-24.9 is associated with the highest levels of CV health. The AHA notes that BMI ranges and the subsequent health risks associated with them may differ among people from diverse racial or ethnic backgrounds or ancestry. This aligns with the World Health Organization recommendations to adjust BMI ranges for people of Asian or Pacific Islander ancestry because recent evidence indicates their risk of conditions such as CVD or type 2 diabetes is higher at a lower BMI.

6. Blood lipids (updated)

The metric for blood lipids (cholesterol and triglycerides) is updated to use non-HDL cholesterol as the preferred number to monitor, rather than total cholesterol. This shift is made because non-HDL cholesterol can be measured without fasting beforehand (thereby increasing its availability at any time of day and implementation at more appointments) and reliably calculated among all people.

7. Blood glucose (updated)

This metric is expanded to include the option of hemoglobin A1c readings or blood glucose levels for people with or without type 1 or 2 diabetes or prediabetes.

8. Blood pressure (no changes)

Blood pressure criteria remain unchanged from 2017 guidance that established levels less than 120/80 mm Hg as optimal, and defined hypertension as 130-139 mm Hg systolic pressure or 80-89 mm Hg diastolic pressure.

‘Concerning’ new data

Results of the first study using Life’s Essential 8 show that the overall CV health of the U.S. population is “well below ideal,” with 80% of adults scoring at a low or moderate level, the researchers report.

Data for the analysis came from 2013-2018 U.S. National Health and Nutrition Examination surveys (NHANES) of more than 13,500 adults aged 20-79 years and nearly 9,900 children aged 2-19 years. Among the key findings:

• The average CV health score based on Life’s Essential 8 was 64.7 for adults and 65.5 for children – in the moderate range on the 0-100 scale.
• Only 0.45% of adults had a perfect score of 100; 20% had high CV health (score of 80 or higher), 63% moderate (score of 50-79), and 18% had low CV health (score of less than 50).
• Adult women had higher average CV health scores (67) compared with men (62.5).
• In general, adults scored lowest in the areas of diet, physical activity, and BMI.
• CV health scores were generally lower at older ages.
• Non-Hispanic Asian Americans had a higher average CV health score than other racial/ethnic groups. Non-Hispanic Whites had the second highest average CV health score, followed, in order, by Hispanic (other than Mexican), Mexican, and non-Hispanic Blacks.
• Children’s diet scores were low, at an average of 40.6.
• Adult sociodemographic groups varied notably in CV health scores for diet, nicotine exposure, blood glucose, and blood pressure.

“These data represent the first look at the cardiovascular health of the U.S. population using the AHA’s new Life’s Essential 8 scoring algorithm,” Dr. Lloyd-Jones said.

“Life’s Essential 8 is a major step forward in our ability to identify when cardiovascular health can be preserved and when it is suboptimal. It should energize efforts to improve cardiovascular health for all people and at every life stage,” Dr. Lloyd-Jones added.

“Analyses like this can help policymakers, communities, clinicians, and the public to understand the opportunities to intervene to improve and maintain optimal cardiovascular health across the life course,” he said.

This research had no commercial funding. The authors have no reported no relevant financial relationships.

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

About 80% of American adults have low to moderate cardiovascular (CV) health based on the American Heart Association checklist for optimal heart health, which now includes healthy sleep as an essential component for heart health.

With the addition of sleep, “Life’s Essential 8” replaces the AHA’s “Life’s Simple 7” checklist.

“The new metric of sleep duration reflects the latest research findings: Sleep impacts overall health, and people who have healthier sleep patterns manage health factors such as weight, blood pressure, or risk for type 2 diabetes more effectively,” AHA President Donald M. Lloyd-Jones, MD, said in a news release.

“In addition, advances in ways to measure sleep, such as with wearable devices, now offer people the ability to reliably and routinely monitor their sleep habits at home,” said Dr. Lloyd-Jones, chair of the department of preventive medicine at Northwestern University in Chicago.

The AHA Presidential Advisory – Life’s Essential 8: Updating and Enhancing the American Heart Association’s Construct on Cardiovascular Health – was published online in the journal Circulation.

A companion paper published simultaneously in Circulation reports the first study using Life’s Essential 8.

Overall, the results show that CV health of the U.S. population is “suboptimal, and we see important differences across age and sociodemographic groups,” Dr. Lloyd-Jones said.
 

Refining Life’s Simple 7

The AHA first defined the seven metrics for optimal CV health in 2010. After 12 years and more than 2,400 scientific papers on the topic, new discoveries in CV health and ways to measure it provided an opportunity to revisit each health component in more detail and provide updates as needed, the AHA explains.

“We felt it was the right time to conduct a comprehensive review of the latest research to refine the existing metrics and consider any new metrics that add value to assessing cardiovascular health for all people,” Dr. Lloyd-Jones said.

Four of the original metrics have been redefined for consistency with newer clinical guidelines or compatibility with new measurement tools, and the scoring system can now also be applied to anyone ages 2 and older. Here is a snapshot of Life’s Essential 8 metrics, including updates.

1. Diet (updated) 

The tool includes a new guide to assess diet quality for adults and children at the individual and population level. At the population level, dietary assessment is based on daily intake of elements in the Dietary Approaches to Stop Hypertension (DASH) eating pattern. For individuals, the Mediterranean Eating Pattern for Americans (MEPA) is used to assess and monitor cardiovascular health.

2. Physical activity (no changes)

Physical activity continues to be measured by the total number of minutes of moderate or vigorous physical activity per week, as defined by the U.S. Physical Activity Guidelines for Americans (2nd edition). The optimal level is 150 minutes (2.5 hours) of moderate physical activity or more per week or 75 minutes per week of vigorous-intensity physical activity for adults; 420 minutes (7 hours) or more per week for children ages 6 and older; and age-specific modifications for younger children.

3. Nicotine exposure (updated)

Use of inhaled nicotine-delivery systems, which includes e-cigarettes or vaping devices, has been added since the previous metric monitored only traditional, combustible cigarettes. This reflects use by adults and youth and their implications on long-term health. Second-hand smoke exposure for children and adults has also been added.

4. Sleep duration (new)

Sleep duration is associated with CV health. Measured by average hours of sleep per night, the ideal level is 7-9 hours daily for adults. Ideal daily sleep ranges for children are 10-16 hours per 24 hours for ages 5 and younger; 9-12 hours for ages 6-12 years; and 8-10 hours for ages 13-18 years.

5. Body mass index (no changes)

The AHA acknowledges that body mass index (BMI) is an imperfect metric. Yet, because it’s easily calculated and widely available, BMI continues as a “reasonable” gauge to assess weight categories that may lead to health problems. BMI of 18.5-24.9 is associated with the highest levels of CV health. The AHA notes that BMI ranges and the subsequent health risks associated with them may differ among people from diverse racial or ethnic backgrounds or ancestry. This aligns with the World Health Organization recommendations to adjust BMI ranges for people of Asian or Pacific Islander ancestry because recent evidence indicates their risk of conditions such as CVD or type 2 diabetes is higher at a lower BMI.

6. Blood lipids (updated)

The metric for blood lipids (cholesterol and triglycerides) is updated to use non-HDL cholesterol as the preferred number to monitor, rather than total cholesterol. This shift is made because non-HDL cholesterol can be measured without fasting beforehand (thereby increasing its availability at any time of day and implementation at more appointments) and reliably calculated among all people.

7. Blood glucose (updated)

This metric is expanded to include the option of hemoglobin A1c readings or blood glucose levels for people with or without type 1 or 2 diabetes or prediabetes.

8. Blood pressure (no changes)

Blood pressure criteria remain unchanged from 2017 guidance that established levels less than 120/80 mm Hg as optimal, and defined hypertension as 130-139 mm Hg systolic pressure or 80-89 mm Hg diastolic pressure.

‘Concerning’ new data

Results of the first study using Life’s Essential 8 show that the overall CV health of the U.S. population is “well below ideal,” with 80% of adults scoring at a low or moderate level, the researchers report.

Data for the analysis came from 2013-2018 U.S. National Health and Nutrition Examination surveys (NHANES) of more than 13,500 adults aged 20-79 years and nearly 9,900 children aged 2-19 years. Among the key findings:

• The average CV health score based on Life’s Essential 8 was 64.7 for adults and 65.5 for children – in the moderate range on the 0-100 scale.
• Only 0.45% of adults had a perfect score of 100; 20% had high CV health (score of 80 or higher), 63% moderate (score of 50-79), and 18% had low CV health (score of less than 50).
• Adult women had higher average CV health scores (67) compared with men (62.5).
• In general, adults scored lowest in the areas of diet, physical activity, and BMI.
• CV health scores were generally lower at older ages.
• Non-Hispanic Asian Americans had a higher average CV health score than other racial/ethnic groups. Non-Hispanic Whites had the second highest average CV health score, followed, in order, by Hispanic (other than Mexican), Mexican, and non-Hispanic Blacks.
• Children’s diet scores were low, at an average of 40.6.
• Adult sociodemographic groups varied notably in CV health scores for diet, nicotine exposure, blood glucose, and blood pressure.

“These data represent the first look at the cardiovascular health of the U.S. population using the AHA’s new Life’s Essential 8 scoring algorithm,” Dr. Lloyd-Jones said.

“Life’s Essential 8 is a major step forward in our ability to identify when cardiovascular health can be preserved and when it is suboptimal. It should energize efforts to improve cardiovascular health for all people and at every life stage,” Dr. Lloyd-Jones added.

“Analyses like this can help policymakers, communities, clinicians, and the public to understand the opportunities to intervene to improve and maintain optimal cardiovascular health across the life course,” he said.

This research had no commercial funding. The authors have no reported no relevant financial relationships.

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

A large meta-analysis sheds light on the best antipsychotic maintenance strategy to prevent relapse in clinically stable schizophrenia – with some unexpected results that have potential implications for changes to current guidelines.

Consistent with the researchers’ hypothesis, continuing antipsychotic treatment at the standard dose, switching to another antipsychotic, and reducing the dose were all significantly more effective than stopping antipsychotic treatment in preventing relapse.

However, contrary to the researchers’ hypothesis, which was based on current literature, switching to another antipsychotic was just as effective as continuing an antipsychotic at the standard dose.

Switching to another antipsychotic “does not increase the risk of relapse. This result was not expected, as previous literature suggested otherwise,” Giovanni Ostuzzi, MD, PhD, with University of Verona (Italy) said in an interview.

“On the other hand, reducing the dose below the standard range used in the acute phase carries a tangible risk of relapse, and should be limited to selected cases, for example those where the risk of withdrawing the treatment altogether is particularly high,” Dr. Ostuzzi said.

“These results should inform evidence-based guidelines, considering that clinical practices for relapse prevention are still heterogeneous and too often guided by clinical common sense only,” he added.

The study was published online in Lancet Psychiatry.
 

Guideline update warranted

The researchers evaluated the effect of different antipsychotic treatment strategies on risk for relapse in a network meta-analysis of 98 randomized controlled trials (RCTs) involving nearly 14,000 patients.

Compared to stopping the antipsychotic, all continuation strategies were effective in preventing relapse.

The risk for relapse was largely (and similarly) reduced when continuing the antipsychotic at the standard dose or switching to a different antipsychotic (relative risk, 0.37 and RR, 0.44, respectively), the researchers found.

Both strategies outperformed the strategy of reducing the antipsychotic dose below the standard (RR, 0.68), which was inferior to the other two strategies.

For every three patients continuing an antipsychotic at standard doses, one additional patient will avoid relapse, compared with patients stopping an antipsychotic, “which can be regarded as a large-effect magnitude according to commonly used thresholds and results from RCTs in acute schizophrenia,” the researchers write.

The number needed to treat (NNT) slightly increased to about 3.5 for patients who switched antipsychotic treatment – “still regarded as a large-effect magnitude,” they note.

“Currently, most psychiatrists are aware of the benefits of continuing antipsychotics in clinically stable individuals. However, they might face the necessity of changing the ongoing treatment strategy, generally because of burdening side effects, poor adherence, or both,” said Dr. Ostuzzi.

“Our findings support updating clinical guidelines to recognize that switching to another antipsychotic during maintenance treatment can be as effective as continuing antipsychotics at standard dose, whereas dose reduction below standard doses should be limited to selected cases,” the investigators write.
 

More to the story

In an accompanying editorial, Marieke J.H. Begemann, PhD, University Medical Center Groningen (the Netherlands) and colleagues note the large number of patients included in the analysis provide “great credibility” to the findings, which are “trustworthy and important, yet only tell part of the story.”

They note that, while tapering information was often missing, antipsychotic discontinuation was probably abrupt for about two-thirds of the included studies. 

“The issue of slow versus swift tapering is not yet settled, as there is a scarcity of RCTs that provide very gradual tapering over several months,” the editorialists write.

To fill this gap, several randomized trials are now in progress to specifically address the effects of gradual tapering or discontinuation vs. antipsychotic maintenance treatment in clinically stable schizophrenia.

“Time is pressing, as patients, their families, and clinicians need evidence-based data to weigh up the risks and benefits of maintaining, switching, or reducing medication with respect to a range of outcomes that are important to them, including social functioning, cognition, physical health, sexual health, and quality of life, thus going well beyond relapse prevention,” the editorialists note.

“Schizophrenia-spectrum disorders are heterogeneous with a largely unpredictable course, and we have known for a long time that a substantial proportion of patients who experienced a first psychosis can manage without antipsychotic medication. The challenge for future research is therefore to identify this subgroup on the basis of individual characteristics and guide them in tapering medication safely,” they add.

The study had no funding source. Dr. Ostuzzi reports no relevant financial relationships. A complete list of author disclosures is available with the original article. The editorialists have reported no relevant financial relationships.

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

A large meta-analysis sheds light on the best antipsychotic maintenance strategy to prevent relapse in clinically stable schizophrenia – with some unexpected results that have potential implications for changes to current guidelines.

Consistent with the researchers’ hypothesis, continuing antipsychotic treatment at the standard dose, switching to another antipsychotic, and reducing the dose were all significantly more effective than stopping antipsychotic treatment in preventing relapse.

However, contrary to the researchers’ hypothesis, which was based on current literature, switching to another antipsychotic was just as effective as continuing an antipsychotic at the standard dose.

Switching to another antipsychotic “does not increase the risk of relapse. This result was not expected, as previous literature suggested otherwise,” Giovanni Ostuzzi, MD, PhD, with University of Verona (Italy) said in an interview.

“On the other hand, reducing the dose below the standard range used in the acute phase carries a tangible risk of relapse, and should be limited to selected cases, for example those where the risk of withdrawing the treatment altogether is particularly high,” Dr. Ostuzzi said.

“These results should inform evidence-based guidelines, considering that clinical practices for relapse prevention are still heterogeneous and too often guided by clinical common sense only,” he added.

The study was published online in Lancet Psychiatry.
 

Guideline update warranted

The researchers evaluated the effect of different antipsychotic treatment strategies on risk for relapse in a network meta-analysis of 98 randomized controlled trials (RCTs) involving nearly 14,000 patients.

Compared to stopping the antipsychotic, all continuation strategies were effective in preventing relapse.

The risk for relapse was largely (and similarly) reduced when continuing the antipsychotic at the standard dose or switching to a different antipsychotic (relative risk, 0.37 and RR, 0.44, respectively), the researchers found.

Both strategies outperformed the strategy of reducing the antipsychotic dose below the standard (RR, 0.68), which was inferior to the other two strategies.

For every three patients continuing an antipsychotic at standard doses, one additional patient will avoid relapse, compared with patients stopping an antipsychotic, “which can be regarded as a large-effect magnitude according to commonly used thresholds and results from RCTs in acute schizophrenia,” the researchers write.

The number needed to treat (NNT) slightly increased to about 3.5 for patients who switched antipsychotic treatment – “still regarded as a large-effect magnitude,” they note.

“Currently, most psychiatrists are aware of the benefits of continuing antipsychotics in clinically stable individuals. However, they might face the necessity of changing the ongoing treatment strategy, generally because of burdening side effects, poor adherence, or both,” said Dr. Ostuzzi.

“Our findings support updating clinical guidelines to recognize that switching to another antipsychotic during maintenance treatment can be as effective as continuing antipsychotics at standard dose, whereas dose reduction below standard doses should be limited to selected cases,” the investigators write.
 

More to the story

In an accompanying editorial, Marieke J.H. Begemann, PhD, University Medical Center Groningen (the Netherlands) and colleagues note the large number of patients included in the analysis provide “great credibility” to the findings, which are “trustworthy and important, yet only tell part of the story.”

They note that, while tapering information was often missing, antipsychotic discontinuation was probably abrupt for about two-thirds of the included studies. 

“The issue of slow versus swift tapering is not yet settled, as there is a scarcity of RCTs that provide very gradual tapering over several months,” the editorialists write.

To fill this gap, several randomized trials are now in progress to specifically address the effects of gradual tapering or discontinuation vs. antipsychotic maintenance treatment in clinically stable schizophrenia.

“Time is pressing, as patients, their families, and clinicians need evidence-based data to weigh up the risks and benefits of maintaining, switching, or reducing medication with respect to a range of outcomes that are important to them, including social functioning, cognition, physical health, sexual health, and quality of life, thus going well beyond relapse prevention,” the editorialists note.

“Schizophrenia-spectrum disorders are heterogeneous with a largely unpredictable course, and we have known for a long time that a substantial proportion of patients who experienced a first psychosis can manage without antipsychotic medication. The challenge for future research is therefore to identify this subgroup on the basis of individual characteristics and guide them in tapering medication safely,” they add.

The study had no funding source. Dr. Ostuzzi reports no relevant financial relationships. A complete list of author disclosures is available with the original article. The editorialists have reported no relevant financial relationships.

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

A large meta-analysis sheds light on the best antipsychotic maintenance strategy to prevent relapse in clinically stable schizophrenia – with some unexpected results that have potential implications for changes to current guidelines.

Consistent with the researchers’ hypothesis, continuing antipsychotic treatment at the standard dose, switching to another antipsychotic, and reducing the dose were all significantly more effective than stopping antipsychotic treatment in preventing relapse.

However, contrary to the researchers’ hypothesis, which was based on current literature, switching to another antipsychotic was just as effective as continuing an antipsychotic at the standard dose.

Switching to another antipsychotic “does not increase the risk of relapse. This result was not expected, as previous literature suggested otherwise,” Giovanni Ostuzzi, MD, PhD, with University of Verona (Italy) said in an interview.

“On the other hand, reducing the dose below the standard range used in the acute phase carries a tangible risk of relapse, and should be limited to selected cases, for example those where the risk of withdrawing the treatment altogether is particularly high,” Dr. Ostuzzi said.

“These results should inform evidence-based guidelines, considering that clinical practices for relapse prevention are still heterogeneous and too often guided by clinical common sense only,” he added.

The study was published online in Lancet Psychiatry.
 

Guideline update warranted

The researchers evaluated the effect of different antipsychotic treatment strategies on risk for relapse in a network meta-analysis of 98 randomized controlled trials (RCTs) involving nearly 14,000 patients.

Compared to stopping the antipsychotic, all continuation strategies were effective in preventing relapse.

The risk for relapse was largely (and similarly) reduced when continuing the antipsychotic at the standard dose or switching to a different antipsychotic (relative risk, 0.37 and RR, 0.44, respectively), the researchers found.

Both strategies outperformed the strategy of reducing the antipsychotic dose below the standard (RR, 0.68), which was inferior to the other two strategies.

For every three patients continuing an antipsychotic at standard doses, one additional patient will avoid relapse, compared with patients stopping an antipsychotic, “which can be regarded as a large-effect magnitude according to commonly used thresholds and results from RCTs in acute schizophrenia,” the researchers write.

The number needed to treat (NNT) slightly increased to about 3.5 for patients who switched antipsychotic treatment – “still regarded as a large-effect magnitude,” they note.

“Currently, most psychiatrists are aware of the benefits of continuing antipsychotics in clinically stable individuals. However, they might face the necessity of changing the ongoing treatment strategy, generally because of burdening side effects, poor adherence, or both,” said Dr. Ostuzzi.

“Our findings support updating clinical guidelines to recognize that switching to another antipsychotic during maintenance treatment can be as effective as continuing antipsychotics at standard dose, whereas dose reduction below standard doses should be limited to selected cases,” the investigators write.
 

More to the story

In an accompanying editorial, Marieke J.H. Begemann, PhD, University Medical Center Groningen (the Netherlands) and colleagues note the large number of patients included in the analysis provide “great credibility” to the findings, which are “trustworthy and important, yet only tell part of the story.”

They note that, while tapering information was often missing, antipsychotic discontinuation was probably abrupt for about two-thirds of the included studies. 

“The issue of slow versus swift tapering is not yet settled, as there is a scarcity of RCTs that provide very gradual tapering over several months,” the editorialists write.

To fill this gap, several randomized trials are now in progress to specifically address the effects of gradual tapering or discontinuation vs. antipsychotic maintenance treatment in clinically stable schizophrenia.

“Time is pressing, as patients, their families, and clinicians need evidence-based data to weigh up the risks and benefits of maintaining, switching, or reducing medication with respect to a range of outcomes that are important to them, including social functioning, cognition, physical health, sexual health, and quality of life, thus going well beyond relapse prevention,” the editorialists note.

“Schizophrenia-spectrum disorders are heterogeneous with a largely unpredictable course, and we have known for a long time that a substantial proportion of patients who experienced a first psychosis can manage without antipsychotic medication. The challenge for future research is therefore to identify this subgroup on the basis of individual characteristics and guide them in tapering medication safely,” they add.

The study had no funding source. Dr. Ostuzzi reports no relevant financial relationships. A complete list of author disclosures is available with the original article. The editorialists have reported no relevant financial relationships.

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