Richard Mark Kirkner

Clinical guidelines for cholesterol management may have two blind spots when it comes to heart attack prevention: Most younger adults with premature coronary artery disease who’ve had a myocardial infarction don’t meet guideline criteria for preventative statin therapy, and survivors under age 55 don’t meet the criteria for continuing nonstatin lipid-lowering treatments, a large single-center retrospective study has shown.

“The classic approach we’ve taken to identifying young adults for prevention is inadequate in younger adults,” corresponding author Ann Marie Navar, MD, PhD, of Duke University, Durham, N.C., said in an interview. “While awaiting more definitive research we should at minimum be using all the tools at our disposal, including broader use of coronary artery calcium [CAC] scoring, to identify young people who may benefit from statin therapy.”

The retrospective observational study analyzed records of 6,639 adults who had cardiac catheterization at Duke University Medical Center from 1995 to 2012 for a first myocardial infarction with obstructive coronary artery disease. The study considered those under age 55 years as “younger” patients, comprising 41% of the study group (2,733); 35% were “middle-aged” at 55-65 years (2,324) and 24% were “older,” at 66-75 years (1,582).

The report, published online Aug. 3 in the Journal of the American College of Cardiology, noted that most of the adults with premature CAD did not meet criteria for preventative statin therapy before their first MI based on ACC/American Heart Association clinical guidelines from 2013 and 2018. It also noted that younger MI survivors are also less frequently eligible for secondary prevention with intensive nonstatin lipid-lowering therapies than are older adults despite a much longer potential life span – and opportunity for another MI – for the former.

The researchers sought to evaluate the real-world implications of changes made in the 2018 guideline for adults who develop premature ischemic heart disease, and found that fewer younger patients qualify for preventative statin therapy under the 2018 guidelines.

“Younger individuals with very high-risk criteria are at higher risk of major adverse cardiovascular events, a finding supporting the appropriate implementation of intensive lipid-lowering therapies in these patients,” wrote lead author Michel Zeitouni, MD, MSc, and colleagues.
 

Key findings

The investigators reported that younger adults were significantly less likely to meet a class I recommendation for statins under the 2013 guideline (42.9%), compared with their middle-aged (70%) and older (82.5%) counterparts; and under the 2018 guideline, at 39.4%, 59.5%, and 77.4%, respectively (both P < .001).

Similarly, when both class I and class IIa recommendations were accounted for, younger patients were significantly less likely than were middle-aged and older patients to be eligible for statins before their index MI under both the 2013 (56.7%, 79.5%, and 85.2%, respectively and 2018 guidelines (46.4%, 73.5%, and 88.2%, respectively (both P < .01).

After their first MI, one in four younger patients (28.3%) met the very high-risk criteria compared with 40% of middle-aged and 81.4% of older patients (P trend < .001). In 8 years of follow-up, patients with very high-risk criteria based on the 2018 guideline had twice the rate of death, nonfatal MI, or stroke (hazard ratio [HR]: 2.15; 95% confidence interval, 1.98-2.33; P < .001).

The researchers acknowledged that the 2018 guideline took the important step of implementing risk enhancers – patient characteristics such as obesity and metabolic syndrome – along with the 10-year atherosclerotic cardiovascular disease (ASCVD) risk score to better identify high-risk young individuals who need statins. However, they also noted that the ability of the guidelines to identify young adults before their first MI “remains suboptimal.”

How to protect younger patients

“The 2018 guidelines will be most effective if we as providers do our best to identify risk enhancers and if we can use CAC scoring more broadly,” Dr. Navar said, noting that although CAC scoring has been shown to improve risk prediction, insurance coverage can be problematic.

“We also need to be careful to screen for the presence of the risk enhancers, such as inflammatory disease, family history, and women-specific risk factors, to make sure we aren’t missing an important high-risk group,” she added.

Other solutions to better identify at-risk younger adults include considering upgrades to the guidelines’ class IIb recommendation to class IIa to emphasize the importance of recognizing lower-risk younger adults, and recommending statins for patients at higher lifetime risk than age- and sex-matched peers, the researchers noted. “In our cohort, young individuals admitted for a first MI had a higher lifetime ASCVD risk score than did patients in the older age categories,” Dr. Zeitouni and colleagues wrote.

Dr. Navar said that these findings are a reminder that guidelines aren’t mandates. “Guidelines are meant to be a starting point for patients and physicians,” she said. “The absence of a recommendation doesn’t mean something isn’t recommended, but that there is not enough data to say one way or another.” 

The study “provides important evidence” that the 2018 guidelines exempted about half of the younger adults who had a first MI from preventative statin therapy, Ron Blankstein, MD, and Avinainder Singh, MD, MMSc, noted in an editorial (J Am Coll Cardiol. 2020;76:665-8).

Brigham and Women&#039;s Hospital

“Data from both the Duke and Young-MI registries should force us to reexamine how we allocate statin use among young individuals,” they noted. Dr. Blankstein is with Brigham and Women’s Hospital, Harvard Medical School, Boston. Dr. Singh is with Yale University, New Haven, Conn.

Dr. Zeitouni reported receiving lecture fees from Bristol-Myers Squibb/Pfizer. Dr. Navar reported financial relationships with Amarin, Janssen, Amgen, Sanofi and Regeneron Pharmaceuticals, AstraZeneca, Esperion, Novo Nordisk, Novartis, The Medicine Company, New Amsterdam, Cerner and Pfizer. Dr. Blankstein reported receiving research support from Amgen. Dr. Singh has no relevant financial relationships to report.

SOURCE: M. Zeitouni et al. J Am Coll Cardiol 2020 Aug 3;76:653-64.

Clinical guidelines for cholesterol management may have two blind spots when it comes to heart attack prevention: Most younger adults with premature coronary artery disease who’ve had a myocardial infarction don’t meet guideline criteria for preventative statin therapy, and survivors under age 55 don’t meet the criteria for continuing nonstatin lipid-lowering treatments, a large single-center retrospective study has shown.

“The classic approach we’ve taken to identifying young adults for prevention is inadequate in younger adults,” corresponding author Ann Marie Navar, MD, PhD, of Duke University, Durham, N.C., said in an interview. “While awaiting more definitive research we should at minimum be using all the tools at our disposal, including broader use of coronary artery calcium [CAC] scoring, to identify young people who may benefit from statin therapy.”

The retrospective observational study analyzed records of 6,639 adults who had cardiac catheterization at Duke University Medical Center from 1995 to 2012 for a first myocardial infarction with obstructive coronary artery disease. The study considered those under age 55 years as “younger” patients, comprising 41% of the study group (2,733); 35% were “middle-aged” at 55-65 years (2,324) and 24% were “older,” at 66-75 years (1,582).

The report, published online Aug. 3 in the Journal of the American College of Cardiology, noted that most of the adults with premature CAD did not meet criteria for preventative statin therapy before their first MI based on ACC/American Heart Association clinical guidelines from 2013 and 2018. It also noted that younger MI survivors are also less frequently eligible for secondary prevention with intensive nonstatin lipid-lowering therapies than are older adults despite a much longer potential life span – and opportunity for another MI – for the former.

The researchers sought to evaluate the real-world implications of changes made in the 2018 guideline for adults who develop premature ischemic heart disease, and found that fewer younger patients qualify for preventative statin therapy under the 2018 guidelines.

“Younger individuals with very high-risk criteria are at higher risk of major adverse cardiovascular events, a finding supporting the appropriate implementation of intensive lipid-lowering therapies in these patients,” wrote lead author Michel Zeitouni, MD, MSc, and colleagues.
 

Key findings

The investigators reported that younger adults were significantly less likely to meet a class I recommendation for statins under the 2013 guideline (42.9%), compared with their middle-aged (70%) and older (82.5%) counterparts; and under the 2018 guideline, at 39.4%, 59.5%, and 77.4%, respectively (both P < .001).

Similarly, when both class I and class IIa recommendations were accounted for, younger patients were significantly less likely than were middle-aged and older patients to be eligible for statins before their index MI under both the 2013 (56.7%, 79.5%, and 85.2%, respectively and 2018 guidelines (46.4%, 73.5%, and 88.2%, respectively (both P < .01).

After their first MI, one in four younger patients (28.3%) met the very high-risk criteria compared with 40% of middle-aged and 81.4% of older patients (P trend < .001). In 8 years of follow-up, patients with very high-risk criteria based on the 2018 guideline had twice the rate of death, nonfatal MI, or stroke (hazard ratio [HR]: 2.15; 95% confidence interval, 1.98-2.33; P < .001).

The researchers acknowledged that the 2018 guideline took the important step of implementing risk enhancers – patient characteristics such as obesity and metabolic syndrome – along with the 10-year atherosclerotic cardiovascular disease (ASCVD) risk score to better identify high-risk young individuals who need statins. However, they also noted that the ability of the guidelines to identify young adults before their first MI “remains suboptimal.”

How to protect younger patients

“The 2018 guidelines will be most effective if we as providers do our best to identify risk enhancers and if we can use CAC scoring more broadly,” Dr. Navar said, noting that although CAC scoring has been shown to improve risk prediction, insurance coverage can be problematic.

“We also need to be careful to screen for the presence of the risk enhancers, such as inflammatory disease, family history, and women-specific risk factors, to make sure we aren’t missing an important high-risk group,” she added.

Other solutions to better identify at-risk younger adults include considering upgrades to the guidelines’ class IIb recommendation to class IIa to emphasize the importance of recognizing lower-risk younger adults, and recommending statins for patients at higher lifetime risk than age- and sex-matched peers, the researchers noted. “In our cohort, young individuals admitted for a first MI had a higher lifetime ASCVD risk score than did patients in the older age categories,” Dr. Zeitouni and colleagues wrote.

Dr. Navar said that these findings are a reminder that guidelines aren’t mandates. “Guidelines are meant to be a starting point for patients and physicians,” she said. “The absence of a recommendation doesn’t mean something isn’t recommended, but that there is not enough data to say one way or another.” 

The study “provides important evidence” that the 2018 guidelines exempted about half of the younger adults who had a first MI from preventative statin therapy, Ron Blankstein, MD, and Avinainder Singh, MD, MMSc, noted in an editorial (J Am Coll Cardiol. 2020;76:665-8).

Brigham and Women&#039;s Hospital

“Data from both the Duke and Young-MI registries should force us to reexamine how we allocate statin use among young individuals,” they noted. Dr. Blankstein is with Brigham and Women’s Hospital, Harvard Medical School, Boston. Dr. Singh is with Yale University, New Haven, Conn.

Dr. Zeitouni reported receiving lecture fees from Bristol-Myers Squibb/Pfizer. Dr. Navar reported financial relationships with Amarin, Janssen, Amgen, Sanofi and Regeneron Pharmaceuticals, AstraZeneca, Esperion, Novo Nordisk, Novartis, The Medicine Company, New Amsterdam, Cerner and Pfizer. Dr. Blankstein reported receiving research support from Amgen. Dr. Singh has no relevant financial relationships to report.

SOURCE: M. Zeitouni et al. J Am Coll Cardiol 2020 Aug 3;76:653-64.

Clinical guidelines for cholesterol management may have two blind spots when it comes to heart attack prevention: Most younger adults with premature coronary artery disease who’ve had a myocardial infarction don’t meet guideline criteria for preventative statin therapy, and survivors under age 55 don’t meet the criteria for continuing nonstatin lipid-lowering treatments, a large single-center retrospective study has shown.

“The classic approach we’ve taken to identifying young adults for prevention is inadequate in younger adults,” corresponding author Ann Marie Navar, MD, PhD, of Duke University, Durham, N.C., said in an interview. “While awaiting more definitive research we should at minimum be using all the tools at our disposal, including broader use of coronary artery calcium [CAC] scoring, to identify young people who may benefit from statin therapy.”

The retrospective observational study analyzed records of 6,639 adults who had cardiac catheterization at Duke University Medical Center from 1995 to 2012 for a first myocardial infarction with obstructive coronary artery disease. The study considered those under age 55 years as “younger” patients, comprising 41% of the study group (2,733); 35% were “middle-aged” at 55-65 years (2,324) and 24% were “older,” at 66-75 years (1,582).

The report, published online Aug. 3 in the Journal of the American College of Cardiology, noted that most of the adults with premature CAD did not meet criteria for preventative statin therapy before their first MI based on ACC/American Heart Association clinical guidelines from 2013 and 2018. It also noted that younger MI survivors are also less frequently eligible for secondary prevention with intensive nonstatin lipid-lowering therapies than are older adults despite a much longer potential life span – and opportunity for another MI – for the former.

The researchers sought to evaluate the real-world implications of changes made in the 2018 guideline for adults who develop premature ischemic heart disease, and found that fewer younger patients qualify for preventative statin therapy under the 2018 guidelines.

“Younger individuals with very high-risk criteria are at higher risk of major adverse cardiovascular events, a finding supporting the appropriate implementation of intensive lipid-lowering therapies in these patients,” wrote lead author Michel Zeitouni, MD, MSc, and colleagues.
 

Key findings

The investigators reported that younger adults were significantly less likely to meet a class I recommendation for statins under the 2013 guideline (42.9%), compared with their middle-aged (70%) and older (82.5%) counterparts; and under the 2018 guideline, at 39.4%, 59.5%, and 77.4%, respectively (both P < .001).

Similarly, when both class I and class IIa recommendations were accounted for, younger patients were significantly less likely than were middle-aged and older patients to be eligible for statins before their index MI under both the 2013 (56.7%, 79.5%, and 85.2%, respectively and 2018 guidelines (46.4%, 73.5%, and 88.2%, respectively (both P < .01).

After their first MI, one in four younger patients (28.3%) met the very high-risk criteria compared with 40% of middle-aged and 81.4% of older patients (P trend < .001). In 8 years of follow-up, patients with very high-risk criteria based on the 2018 guideline had twice the rate of death, nonfatal MI, or stroke (hazard ratio [HR]: 2.15; 95% confidence interval, 1.98-2.33; P < .001).

The researchers acknowledged that the 2018 guideline took the important step of implementing risk enhancers – patient characteristics such as obesity and metabolic syndrome – along with the 10-year atherosclerotic cardiovascular disease (ASCVD) risk score to better identify high-risk young individuals who need statins. However, they also noted that the ability of the guidelines to identify young adults before their first MI “remains suboptimal.”

How to protect younger patients

“The 2018 guidelines will be most effective if we as providers do our best to identify risk enhancers and if we can use CAC scoring more broadly,” Dr. Navar said, noting that although CAC scoring has been shown to improve risk prediction, insurance coverage can be problematic.

“We also need to be careful to screen for the presence of the risk enhancers, such as inflammatory disease, family history, and women-specific risk factors, to make sure we aren’t missing an important high-risk group,” she added.

Other solutions to better identify at-risk younger adults include considering upgrades to the guidelines’ class IIb recommendation to class IIa to emphasize the importance of recognizing lower-risk younger adults, and recommending statins for patients at higher lifetime risk than age- and sex-matched peers, the researchers noted. “In our cohort, young individuals admitted for a first MI had a higher lifetime ASCVD risk score than did patients in the older age categories,” Dr. Zeitouni and colleagues wrote.

Dr. Navar said that these findings are a reminder that guidelines aren’t mandates. “Guidelines are meant to be a starting point for patients and physicians,” she said. “The absence of a recommendation doesn’t mean something isn’t recommended, but that there is not enough data to say one way or another.” 

The study “provides important evidence” that the 2018 guidelines exempted about half of the younger adults who had a first MI from preventative statin therapy, Ron Blankstein, MD, and Avinainder Singh, MD, MMSc, noted in an editorial (J Am Coll Cardiol. 2020;76:665-8).

Brigham and Women&#039;s Hospital

“Data from both the Duke and Young-MI registries should force us to reexamine how we allocate statin use among young individuals,” they noted. Dr. Blankstein is with Brigham and Women’s Hospital, Harvard Medical School, Boston. Dr. Singh is with Yale University, New Haven, Conn.

Dr. Zeitouni reported receiving lecture fees from Bristol-Myers Squibb/Pfizer. Dr. Navar reported financial relationships with Amarin, Janssen, Amgen, Sanofi and Regeneron Pharmaceuticals, AstraZeneca, Esperion, Novo Nordisk, Novartis, The Medicine Company, New Amsterdam, Cerner and Pfizer. Dr. Blankstein reported receiving research support from Amgen. Dr. Singh has no relevant financial relationships to report.

SOURCE: M. Zeitouni et al. J Am Coll Cardiol 2020 Aug 3;76:653-64.

A new scientific statement from the American Heart Association recommends that genetic testing for inherited cardiovascular disease should be reserved for four specific types of heart diseases – cardiomyopathies, thoracic aortic aneurysms and dissections, arrhythmias, and familial hypercholesterolemia – and should enlist skilled geneticists and genetic counselors in the care team.

The guidance comes in a scientific statement published online in the journal Circulation: Genomic and Precision Medicine.

Kiran Musunuru, MD, PhD, MPH, ML, chair of the writing group for the scientific statement, described in an interview the rationale for publishing the statement at this time. “There was no prior single statement that summarized best practices for the whole gamut of inherited cardiovascular diseases in adults, only statements for individual diseases,” he said in an interview. “With genetic testing seeing explosive growth in the past few years, both in the clinical setting and with direct-to-consumer testing, we felt that cardiovascular practitioners would benefit from having a single document to serve as a general resource on genetic testing.”

The statement describes two types of patients who would be suitable for genetic testing for cardiovascular disease (CVD), Dr. Musunuru noted: “Patients who have been diagnosed with or are strongly suspected to have a cardiovascular disease that is often inherited and family members of patients who have been diagnosed with an inherited cardiovascular disease and found by genetic testing to have a mutation that is felt to be the cause of the disease.”

The statement also spells out two crucial elements for genetic testing: thorough disease-specific phenotyping – that is, using genetic information to identify the individual’s disease characteristics and a comprehensive family history that spans at least three generations. Testing should only proceed after patients has had genetic counseling and made a shared decision with their doctors.

“Genetic counseling is absolutely essential both before genetic testing to educate patients on what genetic testing entails and what potential results to expect, as well as the risks of testing; and after genetic testing, to review the results of the genetic testing and explain the potential consequences for the patient’s health and the health of family members, including children,” Dr. Musunuru said.

The process should involve board-certified geneticists or at least cardiovascular specialists well-versed in genetics and genetic counselors, the statement noted. The latter are “critical” in the care team, Dr. Musunuru said.

After the decision is made to do genetic testing, the next step is to decide the scope of the testing. That can range from targeted sequencing of a single gene or a few genes linked to the disease to large gene panels; the latter “may not increase the likelihood of clinically actionable results in adult patients,” Dr. Musunuru and colleagues wrote.

But genetic testing is no guarantee to identify a cause or confirm a diagnosis of CVD, the statement noted. “The yield for any genetic testing for any inherited cardiovascular disease remains <100%, usually much less than 100%,” the writing committee stated.

Dr. Musunuru explained that the results can sometimes be inconclusive. “In many cases, genetic testing reveals a mutation that is uninterpretable, what we call a variant of uncertain significance,” he said. “It is not clear whether the mutation increases the risk of disease or is entirely benign, which makes it very challenging to counsel patients as to whether anything should be done about the mutation.”

Even in a diagnosed patient the test results can be uncertain. “This makes it challenging to explain why the patient has the disease and whether any of the family members are at risk,” Dr. Musunuru said.

According to the statement, providers should encourage patients with a confirmed or likely pathogenic variant for CVD to share that information with “all of their at-risk relative,” the statement noted, suggesting “family letters” given to patients are a way to navigate HIPAA’s privacy limits.

The statement was written on behalf of the American Heart Association’s Council on Genomic and Precision Medicine; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular and Stroke Nursing; and Council on Clinical Cardiology.

Dr. Musunuru and writing group members have no relevant financial relationships to disclose.

SOURCE: Musunuru K et al. Circ Genom Precis Med. 2020 Jul 23. doi: 10.1161/HCG.0000000000000067.

A new scientific statement from the American Heart Association recommends that genetic testing for inherited cardiovascular disease should be reserved for four specific types of heart diseases – cardiomyopathies, thoracic aortic aneurysms and dissections, arrhythmias, and familial hypercholesterolemia – and should enlist skilled geneticists and genetic counselors in the care team.

The guidance comes in a scientific statement published online in the journal Circulation: Genomic and Precision Medicine.

Kiran Musunuru, MD, PhD, MPH, ML, chair of the writing group for the scientific statement, described in an interview the rationale for publishing the statement at this time. “There was no prior single statement that summarized best practices for the whole gamut of inherited cardiovascular diseases in adults, only statements for individual diseases,” he said in an interview. “With genetic testing seeing explosive growth in the past few years, both in the clinical setting and with direct-to-consumer testing, we felt that cardiovascular practitioners would benefit from having a single document to serve as a general resource on genetic testing.”

The statement describes two types of patients who would be suitable for genetic testing for cardiovascular disease (CVD), Dr. Musunuru noted: “Patients who have been diagnosed with or are strongly suspected to have a cardiovascular disease that is often inherited and family members of patients who have been diagnosed with an inherited cardiovascular disease and found by genetic testing to have a mutation that is felt to be the cause of the disease.”

The statement also spells out two crucial elements for genetic testing: thorough disease-specific phenotyping – that is, using genetic information to identify the individual’s disease characteristics and a comprehensive family history that spans at least three generations. Testing should only proceed after patients has had genetic counseling and made a shared decision with their doctors.

“Genetic counseling is absolutely essential both before genetic testing to educate patients on what genetic testing entails and what potential results to expect, as well as the risks of testing; and after genetic testing, to review the results of the genetic testing and explain the potential consequences for the patient’s health and the health of family members, including children,” Dr. Musunuru said.

The process should involve board-certified geneticists or at least cardiovascular specialists well-versed in genetics and genetic counselors, the statement noted. The latter are “critical” in the care team, Dr. Musunuru said.

After the decision is made to do genetic testing, the next step is to decide the scope of the testing. That can range from targeted sequencing of a single gene or a few genes linked to the disease to large gene panels; the latter “may not increase the likelihood of clinically actionable results in adult patients,” Dr. Musunuru and colleagues wrote.

But genetic testing is no guarantee to identify a cause or confirm a diagnosis of CVD, the statement noted. “The yield for any genetic testing for any inherited cardiovascular disease remains <100%, usually much less than 100%,” the writing committee stated.

Dr. Musunuru explained that the results can sometimes be inconclusive. “In many cases, genetic testing reveals a mutation that is uninterpretable, what we call a variant of uncertain significance,” he said. “It is not clear whether the mutation increases the risk of disease or is entirely benign, which makes it very challenging to counsel patients as to whether anything should be done about the mutation.”

Even in a diagnosed patient the test results can be uncertain. “This makes it challenging to explain why the patient has the disease and whether any of the family members are at risk,” Dr. Musunuru said.

According to the statement, providers should encourage patients with a confirmed or likely pathogenic variant for CVD to share that information with “all of their at-risk relative,” the statement noted, suggesting “family letters” given to patients are a way to navigate HIPAA’s privacy limits.

The statement was written on behalf of the American Heart Association’s Council on Genomic and Precision Medicine; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular and Stroke Nursing; and Council on Clinical Cardiology.

Dr. Musunuru and writing group members have no relevant financial relationships to disclose.

SOURCE: Musunuru K et al. Circ Genom Precis Med. 2020 Jul 23. doi: 10.1161/HCG.0000000000000067.

A new scientific statement from the American Heart Association recommends that genetic testing for inherited cardiovascular disease should be reserved for four specific types of heart diseases – cardiomyopathies, thoracic aortic aneurysms and dissections, arrhythmias, and familial hypercholesterolemia – and should enlist skilled geneticists and genetic counselors in the care team.

The guidance comes in a scientific statement published online in the journal Circulation: Genomic and Precision Medicine.

Kiran Musunuru, MD, PhD, MPH, ML, chair of the writing group for the scientific statement, described in an interview the rationale for publishing the statement at this time. “There was no prior single statement that summarized best practices for the whole gamut of inherited cardiovascular diseases in adults, only statements for individual diseases,” he said in an interview. “With genetic testing seeing explosive growth in the past few years, both in the clinical setting and with direct-to-consumer testing, we felt that cardiovascular practitioners would benefit from having a single document to serve as a general resource on genetic testing.”

The statement describes two types of patients who would be suitable for genetic testing for cardiovascular disease (CVD), Dr. Musunuru noted: “Patients who have been diagnosed with or are strongly suspected to have a cardiovascular disease that is often inherited and family members of patients who have been diagnosed with an inherited cardiovascular disease and found by genetic testing to have a mutation that is felt to be the cause of the disease.”

The statement also spells out two crucial elements for genetic testing: thorough disease-specific phenotyping – that is, using genetic information to identify the individual’s disease characteristics and a comprehensive family history that spans at least three generations. Testing should only proceed after patients has had genetic counseling and made a shared decision with their doctors.

“Genetic counseling is absolutely essential both before genetic testing to educate patients on what genetic testing entails and what potential results to expect, as well as the risks of testing; and after genetic testing, to review the results of the genetic testing and explain the potential consequences for the patient’s health and the health of family members, including children,” Dr. Musunuru said.

The process should involve board-certified geneticists or at least cardiovascular specialists well-versed in genetics and genetic counselors, the statement noted. The latter are “critical” in the care team, Dr. Musunuru said.

After the decision is made to do genetic testing, the next step is to decide the scope of the testing. That can range from targeted sequencing of a single gene or a few genes linked to the disease to large gene panels; the latter “may not increase the likelihood of clinically actionable results in adult patients,” Dr. Musunuru and colleagues wrote.

But genetic testing is no guarantee to identify a cause or confirm a diagnosis of CVD, the statement noted. “The yield for any genetic testing for any inherited cardiovascular disease remains <100%, usually much less than 100%,” the writing committee stated.

Dr. Musunuru explained that the results can sometimes be inconclusive. “In many cases, genetic testing reveals a mutation that is uninterpretable, what we call a variant of uncertain significance,” he said. “It is not clear whether the mutation increases the risk of disease or is entirely benign, which makes it very challenging to counsel patients as to whether anything should be done about the mutation.”

Even in a diagnosed patient the test results can be uncertain. “This makes it challenging to explain why the patient has the disease and whether any of the family members are at risk,” Dr. Musunuru said.

According to the statement, providers should encourage patients with a confirmed or likely pathogenic variant for CVD to share that information with “all of their at-risk relative,” the statement noted, suggesting “family letters” given to patients are a way to navigate HIPAA’s privacy limits.

The statement was written on behalf of the American Heart Association’s Council on Genomic and Precision Medicine; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular and Stroke Nursing; and Council on Clinical Cardiology.

Dr. Musunuru and writing group members have no relevant financial relationships to disclose.

SOURCE: Musunuru K et al. Circ Genom Precis Med. 2020 Jul 23. doi: 10.1161/HCG.0000000000000067.

A secondary analysis of a major study of polypill therapy for hypertension found that patients who don’t reach blood pressure targets are less likely to have their medications adjusted if they’re on fixed-dose combination therapy.

However, hypertension patients on low-dose, triple-pill combination therapy are more likely to achieve blood pressure control than are those on usual care.

The secondary analysis of Triple Pill vs. Usual Care Management for Patients with Mild-to-Moderate Hypertension (TRIUMPH) was published online in JAMA Cardiology (2020 Jul 22. doi: 10.1001/jamacardio.2020.2739). The trial randomized 700 patients with hypertension in Sri Lanka to triple-pill fixed-dose combination (FDC) therapy or usual care during February 2016–May 2017, with follow-up ending in October 2017.

A greater proportion of FDC patients reached target BP by the end of the study compared with usual care, 70% vs. 55%. However, the study found that therapeutic inertia – the failure to intensify therapy in nonresponsive patients – was more common in the FDC group at 6- and 12-week follow-up: 87% vs. 64% and 90% vs. 65%, respectively; both differences were significant different at P < .001).

The once-daily FDC pill contained telmisartan 20 mg, amlodipine 2.5 mg; and chlorthalidone 12.5 mg.

“Using a triple low-dose combination blood-pressure pill reduced the need to uptitrate BP therapy as more patients are at target, but doctors were less likely to uptitrate with triple-pill therapy when it was needed,” lead author Nelson Wang, MD, a research fellow at the George Institute for Global Health in suburban Sydney, said in an interview.

“Overall, there were fewer treatment inertia episodes in the triple-pill group than in the usual care group, but this was driven by the fact that fewer triple-pill patients needed uptitration when coming to their follow-up visits,” Dr. Wang added.

The analysis found that clinicians who prescribed triple-pill FDC used 23 unique drug treatment regimens per 100 treated patients compared with 54 different regiments with usual care (P < .001). “There was a large simplification in care,” Dr. Wang said of the FDC approach.

Dr. Wang and colleagues called for greater efforts to address therapeutic inertia, particularly with FDC therapies, and suggested potential strategies consisting of patient education, incentives for appropriate treatment adjustments, and feedback mechanisms and reminders for physicians.

“There may also be a need for more dosage options with the FDC triple pill to allow physicians to intensify therapy without fear of overtreatment and adverse drug effects,” they wrote.

In an accompanying editorial (JAMA Cardiol. 2020 Jul 22. doi: 10.1001/jamacardio.2020.2693), Ann Marie Navar, MD, PhD, associate professor of cardiology at Duke Clinical Research Institute, Durham, N.C., noted that initiating treatment with FDC therapy doesn’t preclude a more personalized approach for patients who don’t achieve their BP target. “The real choice now is the choice of initial treatment,” she wrote, adding that future treatment guidelines should consider extending an FDC-first approach to patients with less severe levels of hypertension.

“The study showed there’s room for a both a population-based fixed-drug combination approach and a personalized approach to how we think about hypertension management with fixed-dose therapy,” she said in an interview. “It’s not a one-and-done situation.”

Dr. Wang has no financial relationships to disclose. Study coauthors received funding from the Australian National Health and Medical Research Council and the U.K. National Institute for Health Research. Dr. Navar has no relevant financial relationships to report.

SOURCE: Wang N et al. JAMA Cardiol. 2020. doi: 10.1001/jamacardio.2020.2739.

A secondary analysis of a major study of polypill therapy for hypertension found that patients who don’t reach blood pressure targets are less likely to have their medications adjusted if they’re on fixed-dose combination therapy.

However, hypertension patients on low-dose, triple-pill combination therapy are more likely to achieve blood pressure control than are those on usual care.

The secondary analysis of Triple Pill vs. Usual Care Management for Patients with Mild-to-Moderate Hypertension (TRIUMPH) was published online in JAMA Cardiology (2020 Jul 22. doi: 10.1001/jamacardio.2020.2739). The trial randomized 700 patients with hypertension in Sri Lanka to triple-pill fixed-dose combination (FDC) therapy or usual care during February 2016–May 2017, with follow-up ending in October 2017.

A greater proportion of FDC patients reached target BP by the end of the study compared with usual care, 70% vs. 55%. However, the study found that therapeutic inertia – the failure to intensify therapy in nonresponsive patients – was more common in the FDC group at 6- and 12-week follow-up: 87% vs. 64% and 90% vs. 65%, respectively; both differences were significant different at P < .001).

The once-daily FDC pill contained telmisartan 20 mg, amlodipine 2.5 mg; and chlorthalidone 12.5 mg.

“Using a triple low-dose combination blood-pressure pill reduced the need to uptitrate BP therapy as more patients are at target, but doctors were less likely to uptitrate with triple-pill therapy when it was needed,” lead author Nelson Wang, MD, a research fellow at the George Institute for Global Health in suburban Sydney, said in an interview.

“Overall, there were fewer treatment inertia episodes in the triple-pill group than in the usual care group, but this was driven by the fact that fewer triple-pill patients needed uptitration when coming to their follow-up visits,” Dr. Wang added.

The analysis found that clinicians who prescribed triple-pill FDC used 23 unique drug treatment regimens per 100 treated patients compared with 54 different regiments with usual care (P < .001). “There was a large simplification in care,” Dr. Wang said of the FDC approach.

Dr. Wang and colleagues called for greater efforts to address therapeutic inertia, particularly with FDC therapies, and suggested potential strategies consisting of patient education, incentives for appropriate treatment adjustments, and feedback mechanisms and reminders for physicians.

“There may also be a need for more dosage options with the FDC triple pill to allow physicians to intensify therapy without fear of overtreatment and adverse drug effects,” they wrote.

In an accompanying editorial (JAMA Cardiol. 2020 Jul 22. doi: 10.1001/jamacardio.2020.2693), Ann Marie Navar, MD, PhD, associate professor of cardiology at Duke Clinical Research Institute, Durham, N.C., noted that initiating treatment with FDC therapy doesn’t preclude a more personalized approach for patients who don’t achieve their BP target. “The real choice now is the choice of initial treatment,” she wrote, adding that future treatment guidelines should consider extending an FDC-first approach to patients with less severe levels of hypertension.

“The study showed there’s room for a both a population-based fixed-drug combination approach and a personalized approach to how we think about hypertension management with fixed-dose therapy,” she said in an interview. “It’s not a one-and-done situation.”

Dr. Wang has no financial relationships to disclose. Study coauthors received funding from the Australian National Health and Medical Research Council and the U.K. National Institute for Health Research. Dr. Navar has no relevant financial relationships to report.

SOURCE: Wang N et al. JAMA Cardiol. 2020. doi: 10.1001/jamacardio.2020.2739.

A secondary analysis of a major study of polypill therapy for hypertension found that patients who don’t reach blood pressure targets are less likely to have their medications adjusted if they’re on fixed-dose combination therapy.

However, hypertension patients on low-dose, triple-pill combination therapy are more likely to achieve blood pressure control than are those on usual care.

The secondary analysis of Triple Pill vs. Usual Care Management for Patients with Mild-to-Moderate Hypertension (TRIUMPH) was published online in JAMA Cardiology (2020 Jul 22. doi: 10.1001/jamacardio.2020.2739). The trial randomized 700 patients with hypertension in Sri Lanka to triple-pill fixed-dose combination (FDC) therapy or usual care during February 2016–May 2017, with follow-up ending in October 2017.

A greater proportion of FDC patients reached target BP by the end of the study compared with usual care, 70% vs. 55%. However, the study found that therapeutic inertia – the failure to intensify therapy in nonresponsive patients – was more common in the FDC group at 6- and 12-week follow-up: 87% vs. 64% and 90% vs. 65%, respectively; both differences were significant different at P < .001).

The once-daily FDC pill contained telmisartan 20 mg, amlodipine 2.5 mg; and chlorthalidone 12.5 mg.

“Using a triple low-dose combination blood-pressure pill reduced the need to uptitrate BP therapy as more patients are at target, but doctors were less likely to uptitrate with triple-pill therapy when it was needed,” lead author Nelson Wang, MD, a research fellow at the George Institute for Global Health in suburban Sydney, said in an interview.

“Overall, there were fewer treatment inertia episodes in the triple-pill group than in the usual care group, but this was driven by the fact that fewer triple-pill patients needed uptitration when coming to their follow-up visits,” Dr. Wang added.

The analysis found that clinicians who prescribed triple-pill FDC used 23 unique drug treatment regimens per 100 treated patients compared with 54 different regiments with usual care (P < .001). “There was a large simplification in care,” Dr. Wang said of the FDC approach.

Dr. Wang and colleagues called for greater efforts to address therapeutic inertia, particularly with FDC therapies, and suggested potential strategies consisting of patient education, incentives for appropriate treatment adjustments, and feedback mechanisms and reminders for physicians.

“There may also be a need for more dosage options with the FDC triple pill to allow physicians to intensify therapy without fear of overtreatment and adverse drug effects,” they wrote.

In an accompanying editorial (JAMA Cardiol. 2020 Jul 22. doi: 10.1001/jamacardio.2020.2693), Ann Marie Navar, MD, PhD, associate professor of cardiology at Duke Clinical Research Institute, Durham, N.C., noted that initiating treatment with FDC therapy doesn’t preclude a more personalized approach for patients who don’t achieve their BP target. “The real choice now is the choice of initial treatment,” she wrote, adding that future treatment guidelines should consider extending an FDC-first approach to patients with less severe levels of hypertension.

“The study showed there’s room for a both a population-based fixed-drug combination approach and a personalized approach to how we think about hypertension management with fixed-dose therapy,” she said in an interview. “It’s not a one-and-done situation.”

Dr. Wang has no financial relationships to disclose. Study coauthors received funding from the Australian National Health and Medical Research Council and the U.K. National Institute for Health Research. Dr. Navar has no relevant financial relationships to report.

SOURCE: Wang N et al. JAMA Cardiol. 2020. doi: 10.1001/jamacardio.2020.2739.

Nausea, vomiting, and diarrhea are gastrointestinal symptoms that COVID-19 patients have had, and up to 30% have been reported to have liver symptoms. Because patients with these symptoms may require endoscopy, the American Gastroenterological Association has issued a rapid recommendation document that advises physicians and health care workers to use N95 masks, double gloves, and negative-pressure rooms when performing GI procedures during the COVID-19 pandemic.

The recommendations, published in Gastroenterology (2020. doi: 10.1053/j.gastro.2020.03.072), also cover non–COVID-19 patients and situations where N95 masks should be used, offer guidelines for triaging patients for endoscopy and timing of nonurgent procedures, and evaluate the latest evidence in the incidence of GI and liver manifestations of COVID-19. The guideline panel met in March.

The document includes seven recommendations for use of personal protective equipment by physicians and nurses performing GI procedures. The recommendations and the level of evidence supporting them fall under four categories:

1. Masks, comprising four recommendations: use of N95 masks for upper and lower GI procedures regardless of a patient’s COVID-19 status; no use of only surgical masks in confirmed COVID-19 patients or suspected cases; and use of reused N95 masks when fresh ones aren’t available instead of using a surgical mask only (very low to moderate level of evidence depending on the recommendation).

2. Double-gloving when performing any GI procedure regardless of the patient’s COVID-19 status (moderate quality evidence).

3. When available, a negative-pressure room for any COVID-19 patient or suspect rather than a regular endoscopy room (very low certainty of evidence).

4. Standard cleaning, endoscopic disinfection, and reprocessing protocols regardless of a patient’s COVID-19 status (good practice statement).

For decontamination, the panel noted that commonly used biocidal agents, such as hydrogen peroxide, alcohols, sodium hypochlorite, or benzalkonium chloride have proved effective for decontaminating of coronavirus.

For implementing the PPE recommendations, the panel stated that personnel still need to practice don and doff standard protocols, and that N95 masks should be fitted for each individual.

Other steps include banning personal belongings in the procedure area; minimizing the number of personnel in the room; avoiding change of personnel and keeping nonprocedural personnel out during the procedure; considering use of nursing teams that follow the patient through preprocedure, procedure, and recovery, and considering having endoscopy teams remain together during the day to minimize exposure.

The triage recommendations stated that “trained medical personnel” should review all procedures and categorize them as time-sensitive or not time-sensitive, based on a framework the recommendation includes. In “an open-access endoscopy system” when there isn’t enough information to determine timing for the procedure, the recommendation provides a three-step approach: a phone consult with the referring physician, a telehealth visit with the patient, or a multidisciplinary team approach or virtual disease/tumor board.

“The proposed framework of separating procedures into time-sensitive and non–time-sensitive cases may be useful in determining which procedures if delayed may negatively impact on patient-important outcomes,” wrote Shahnaz Sultan, MD, AGAF, of the University of Minnesota, Minneapolis, and colleagues. The panel noted decision-making should focus on “patient-important outcomes.”

For nonurgent procedures, the panel arrived at a consensus that 8 weeks was an appropriate window for reassessment of deferred procedures, depending on the availability of resources and if the time-sensitivity of the procedure changes.

The panel also attempted to determine the likelihood of GI and liver manifestations of COVID-19 by evaluating published cohort studies. They found that 2%-13.8% of patients had diarrhea, 1%-10.1% had nausea or vomiting, and one study reported 2% had abdominal pain (Am J Gastroenterol. 2020 May;115[5]766-73). What’s more, some studies have shown stool samples positive for SARS-CoV-2 RNA even after respiratory samples were negative.

The evidence on liver manifestations isn’t as robust, but one study reported that 20%-30% of patients had liver injury upon diagnosis of COVID-19 (Gastroenterology. 2020;158:1518-9), and that severe hepatitis has been reported but liver failure seems rare (Lancet. 2020 Feb 15;395[10223]:507-13). “The pattern of liver injury appears to be predominantly hepatocellular, and the etiology remains uncertain but may represent a secondary effect of the systemic inflammatory response observed with COVID-19 disease, although direct viral infection and drug-induced liver injury cannot be excluded,” Dr. Sultan and colleagues noted.

There were no relevant author conflicts of interest. The American Gastroenterological Association (AGA) Institute funded the study.

SOURCE: Sultan S et al. Gastroenterology. 2020. doi: 10.1053/j.gastro.2020.03.072.

Check out the AGA COVID-19 Resource Library for new clinical guidance, education, research and physician resources, including recent guidance on how to treat patients with IBD during the pandemic, at www.gastro.org/covid.

Nausea, vomiting, and diarrhea are gastrointestinal symptoms that COVID-19 patients have had, and up to 30% have been reported to have liver symptoms. Because patients with these symptoms may require endoscopy, the American Gastroenterological Association has issued a rapid recommendation document that advises physicians and health care workers to use N95 masks, double gloves, and negative-pressure rooms when performing GI procedures during the COVID-19 pandemic.

The recommendations, published in Gastroenterology (2020. doi: 10.1053/j.gastro.2020.03.072), also cover non–COVID-19 patients and situations where N95 masks should be used, offer guidelines for triaging patients for endoscopy and timing of nonurgent procedures, and evaluate the latest evidence in the incidence of GI and liver manifestations of COVID-19. The guideline panel met in March.

The document includes seven recommendations for use of personal protective equipment by physicians and nurses performing GI procedures. The recommendations and the level of evidence supporting them fall under four categories:

1. Masks, comprising four recommendations: use of N95 masks for upper and lower GI procedures regardless of a patient’s COVID-19 status; no use of only surgical masks in confirmed COVID-19 patients or suspected cases; and use of reused N95 masks when fresh ones aren’t available instead of using a surgical mask only (very low to moderate level of evidence depending on the recommendation).

2. Double-gloving when performing any GI procedure regardless of the patient’s COVID-19 status (moderate quality evidence).

3. When available, a negative-pressure room for any COVID-19 patient or suspect rather than a regular endoscopy room (very low certainty of evidence).

4. Standard cleaning, endoscopic disinfection, and reprocessing protocols regardless of a patient’s COVID-19 status (good practice statement).

For decontamination, the panel noted that commonly used biocidal agents, such as hydrogen peroxide, alcohols, sodium hypochlorite, or benzalkonium chloride have proved effective for decontaminating of coronavirus.

For implementing the PPE recommendations, the panel stated that personnel still need to practice don and doff standard protocols, and that N95 masks should be fitted for each individual.

Other steps include banning personal belongings in the procedure area; minimizing the number of personnel in the room; avoiding change of personnel and keeping nonprocedural personnel out during the procedure; considering use of nursing teams that follow the patient through preprocedure, procedure, and recovery, and considering having endoscopy teams remain together during the day to minimize exposure.

The triage recommendations stated that “trained medical personnel” should review all procedures and categorize them as time-sensitive or not time-sensitive, based on a framework the recommendation includes. In “an open-access endoscopy system” when there isn’t enough information to determine timing for the procedure, the recommendation provides a three-step approach: a phone consult with the referring physician, a telehealth visit with the patient, or a multidisciplinary team approach or virtual disease/tumor board.

“The proposed framework of separating procedures into time-sensitive and non–time-sensitive cases may be useful in determining which procedures if delayed may negatively impact on patient-important outcomes,” wrote Shahnaz Sultan, MD, AGAF, of the University of Minnesota, Minneapolis, and colleagues. The panel noted decision-making should focus on “patient-important outcomes.”

For nonurgent procedures, the panel arrived at a consensus that 8 weeks was an appropriate window for reassessment of deferred procedures, depending on the availability of resources and if the time-sensitivity of the procedure changes.

The panel also attempted to determine the likelihood of GI and liver manifestations of COVID-19 by evaluating published cohort studies. They found that 2%-13.8% of patients had diarrhea, 1%-10.1% had nausea or vomiting, and one study reported 2% had abdominal pain (Am J Gastroenterol. 2020 May;115[5]766-73). What’s more, some studies have shown stool samples positive for SARS-CoV-2 RNA even after respiratory samples were negative.

The evidence on liver manifestations isn’t as robust, but one study reported that 20%-30% of patients had liver injury upon diagnosis of COVID-19 (Gastroenterology. 2020;158:1518-9), and that severe hepatitis has been reported but liver failure seems rare (Lancet. 2020 Feb 15;395[10223]:507-13). “The pattern of liver injury appears to be predominantly hepatocellular, and the etiology remains uncertain but may represent a secondary effect of the systemic inflammatory response observed with COVID-19 disease, although direct viral infection and drug-induced liver injury cannot be excluded,” Dr. Sultan and colleagues noted.

There were no relevant author conflicts of interest. The American Gastroenterological Association (AGA) Institute funded the study.

SOURCE: Sultan S et al. Gastroenterology. 2020. doi: 10.1053/j.gastro.2020.03.072.

Check out the AGA COVID-19 Resource Library for new clinical guidance, education, research and physician resources, including recent guidance on how to treat patients with IBD during the pandemic, at www.gastro.org/covid.

Nausea, vomiting, and diarrhea are gastrointestinal symptoms that COVID-19 patients have had, and up to 30% have been reported to have liver symptoms. Because patients with these symptoms may require endoscopy, the American Gastroenterological Association has issued a rapid recommendation document that advises physicians and health care workers to use N95 masks, double gloves, and negative-pressure rooms when performing GI procedures during the COVID-19 pandemic.

The recommendations, published in Gastroenterology (2020. doi: 10.1053/j.gastro.2020.03.072), also cover non–COVID-19 patients and situations where N95 masks should be used, offer guidelines for triaging patients for endoscopy and timing of nonurgent procedures, and evaluate the latest evidence in the incidence of GI and liver manifestations of COVID-19. The guideline panel met in March.

The document includes seven recommendations for use of personal protective equipment by physicians and nurses performing GI procedures. The recommendations and the level of evidence supporting them fall under four categories:

1. Masks, comprising four recommendations: use of N95 masks for upper and lower GI procedures regardless of a patient’s COVID-19 status; no use of only surgical masks in confirmed COVID-19 patients or suspected cases; and use of reused N95 masks when fresh ones aren’t available instead of using a surgical mask only (very low to moderate level of evidence depending on the recommendation).

2. Double-gloving when performing any GI procedure regardless of the patient’s COVID-19 status (moderate quality evidence).

3. When available, a negative-pressure room for any COVID-19 patient or suspect rather than a regular endoscopy room (very low certainty of evidence).

4. Standard cleaning, endoscopic disinfection, and reprocessing protocols regardless of a patient’s COVID-19 status (good practice statement).

For decontamination, the panel noted that commonly used biocidal agents, such as hydrogen peroxide, alcohols, sodium hypochlorite, or benzalkonium chloride have proved effective for decontaminating of coronavirus.

For implementing the PPE recommendations, the panel stated that personnel still need to practice don and doff standard protocols, and that N95 masks should be fitted for each individual.

Other steps include banning personal belongings in the procedure area; minimizing the number of personnel in the room; avoiding change of personnel and keeping nonprocedural personnel out during the procedure; considering use of nursing teams that follow the patient through preprocedure, procedure, and recovery, and considering having endoscopy teams remain together during the day to minimize exposure.

The triage recommendations stated that “trained medical personnel” should review all procedures and categorize them as time-sensitive or not time-sensitive, based on a framework the recommendation includes. In “an open-access endoscopy system” when there isn’t enough information to determine timing for the procedure, the recommendation provides a three-step approach: a phone consult with the referring physician, a telehealth visit with the patient, or a multidisciplinary team approach or virtual disease/tumor board.

“The proposed framework of separating procedures into time-sensitive and non–time-sensitive cases may be useful in determining which procedures if delayed may negatively impact on patient-important outcomes,” wrote Shahnaz Sultan, MD, AGAF, of the University of Minnesota, Minneapolis, and colleagues. The panel noted decision-making should focus on “patient-important outcomes.”

For nonurgent procedures, the panel arrived at a consensus that 8 weeks was an appropriate window for reassessment of deferred procedures, depending on the availability of resources and if the time-sensitivity of the procedure changes.

The panel also attempted to determine the likelihood of GI and liver manifestations of COVID-19 by evaluating published cohort studies. They found that 2%-13.8% of patients had diarrhea, 1%-10.1% had nausea or vomiting, and one study reported 2% had abdominal pain (Am J Gastroenterol. 2020 May;115[5]766-73). What’s more, some studies have shown stool samples positive for SARS-CoV-2 RNA even after respiratory samples were negative.

The evidence on liver manifestations isn’t as robust, but one study reported that 20%-30% of patients had liver injury upon diagnosis of COVID-19 (Gastroenterology. 2020;158:1518-9), and that severe hepatitis has been reported but liver failure seems rare (Lancet. 2020 Feb 15;395[10223]:507-13). “The pattern of liver injury appears to be predominantly hepatocellular, and the etiology remains uncertain but may represent a secondary effect of the systemic inflammatory response observed with COVID-19 disease, although direct viral infection and drug-induced liver injury cannot be excluded,” Dr. Sultan and colleagues noted.

There were no relevant author conflicts of interest. The American Gastroenterological Association (AGA) Institute funded the study.

SOURCE: Sultan S et al. Gastroenterology. 2020. doi: 10.1053/j.gastro.2020.03.072.

Check out the AGA COVID-19 Resource Library for new clinical guidance, education, research and physician resources, including recent guidance on how to treat patients with IBD during the pandemic, at www.gastro.org/covid.

People with high-frequency episodic migraine and low-frequency chronic migraine may have similar treatment needs because characteristics of the two disorders overlap significantly, calling into question the existing threshold of 15 migraine headache days per month to distinguish low- and high-frequency migraine, according to an analysis of almost 17,000 patients from the Chronic Migraine Epidemiology and Outcomes (CaMEO) study presented at the virtual annual meeting of the American Headache Society.

“The results showed substantial overlap in levels of burden, anxiety, depression and health utilization, including outpatient, inpatient and emergency department visits, among CaMEO respondents with high-frequency episodic migraine and those with low-frequency chronic migraine,” said Richard B. Lipton, MD, of the Albert Einstein College of Medicine, New York.

The study analyzed data on 16,789 respondents to CaMEO, the longitudinal, web-based study designed to characterize the course of episodic and chronic migraine. The study population consisted of four subgroups based on the number of self-reporting monthly headache days (MHDs):

• Low- and moderate-frequency episodic migraine (LFEM; zero to seven MHDs; n = 13,473).
• High-frequency episodic migraine (HFEM; 8-14 MHDs; n = 1,840).
• Low-frequency chronic migraine (LFCM; 15-23 MHDs; n = 1,035).
• High-frequency chronic migraine (HFCM; 24 or more MHDs; n = 441).

Dr. Lipton pointed out that the International Classification of Headache Disorders, 3rd edition, defines chronic migraine as 15 or more MHDs for 3 months or more with criteria for migraine with or without aura met on 8 days a month or more. It defines episodic migraine as less than 15 MHDs.

The study characterized migraine subgroups by various demographics. “The more frequent headache categories were associated with slightly older age of onset with a higher proportion of BMI [body mass index] in the obese range and overall with lower levels of household income and education,” Dr. Lipton said.
 

Similar headache characteristics

A comparison of headache characteristics and headache-related disabilities across subgroups revealed a number of commonalities between the HFEM and LFCM subgroups, Dr. Lipton said. Among them were presence of mild to severe allodynia, disability grade, interictal burden, and anxiety and depression scores. For example, 47.3% of the HFEM subgroup and 54.9% of the LFCM subgroup had Patient Health Questionnaire–9 depression test scores greater than 10.

The study also evaluated patterns of consultation, diagnosis, and health resource utilization and found similar rates between the HFEM and LCFM subgroups, Dr. Lipton said. Rates of overnight hospital stay in the past 6 months were almost identical between the two subgroups: 4.1% for the former and 4.2% for the latter. One striking difference between the two subgroups: the rate of medication overuse per ICHD-3 recommendations was 40.5% in HFEM and 63% in LFCM.

“These finding suggest that the treatment needs of people with HFEM may be similar to those of people with LFCM, suggesting that the 15-MHD threshold currently recommended by the ICHD-3 may merit reconsideration,” Dr. Lipton said.
 

An arbitrary cutoff?

The findings raise a valid point about reevaluating the thresholds for low- and high-frequency migraine, said Andrew Charles, MD, director of the Goldberg Migraine Program at the University of California, Los Angeles. “My own personal view is that they’re the same thing,” he said of HFEM and LFCM; The 15-day cutoff, he said, is “somewhat arbitrary.”

Dr. Charles suggested migraine categories address frequency and not characteristics – episodic versus chronic – and use a range rather than a threshold. “Define a range that’s more like 10-20 days per month rather than having that point at 15,” Dr. Charles said. “People sometimes make the mistake of thinking that that classification reflects some underlying pathophysiology, and that may not be necessarily true.”

Dr. Lipton disclosed financial relationships with Alder Biopharmaceuticals, Allergan (now AbbVie), Amgen, Biohaven Pharmaceuticals, Dr. Reddy’s/Promius, Electrocore, Eli Lilly, eNeura Therapeutics, GlaxoSmithKline, Lundbeck (Alder), Merck, Pernix Therapeutics, Pfizer, Supernus, Teva, Trigemina, Axsome Therapeutics, Vector, and Vedanta. Dr. Charles disclosed he is a consultant to Amgen, Biohaven Pharmaceuticals, Eli Lilly, Lundbeck, and Novartis.

People with high-frequency episodic migraine and low-frequency chronic migraine may have similar treatment needs because characteristics of the two disorders overlap significantly, calling into question the existing threshold of 15 migraine headache days per month to distinguish low- and high-frequency migraine, according to an analysis of almost 17,000 patients from the Chronic Migraine Epidemiology and Outcomes (CaMEO) study presented at the virtual annual meeting of the American Headache Society.

“The results showed substantial overlap in levels of burden, anxiety, depression and health utilization, including outpatient, inpatient and emergency department visits, among CaMEO respondents with high-frequency episodic migraine and those with low-frequency chronic migraine,” said Richard B. Lipton, MD, of the Albert Einstein College of Medicine, New York.

The study analyzed data on 16,789 respondents to CaMEO, the longitudinal, web-based study designed to characterize the course of episodic and chronic migraine. The study population consisted of four subgroups based on the number of self-reporting monthly headache days (MHDs):

• Low- and moderate-frequency episodic migraine (LFEM; zero to seven MHDs; n = 13,473).
• High-frequency episodic migraine (HFEM; 8-14 MHDs; n = 1,840).
• Low-frequency chronic migraine (LFCM; 15-23 MHDs; n = 1,035).
• High-frequency chronic migraine (HFCM; 24 or more MHDs; n = 441).

Dr. Lipton pointed out that the International Classification of Headache Disorders, 3rd edition, defines chronic migraine as 15 or more MHDs for 3 months or more with criteria for migraine with or without aura met on 8 days a month or more. It defines episodic migraine as less than 15 MHDs.

The study characterized migraine subgroups by various demographics. “The more frequent headache categories were associated with slightly older age of onset with a higher proportion of BMI [body mass index] in the obese range and overall with lower levels of household income and education,” Dr. Lipton said.
 

Similar headache characteristics

A comparison of headache characteristics and headache-related disabilities across subgroups revealed a number of commonalities between the HFEM and LFCM subgroups, Dr. Lipton said. Among them were presence of mild to severe allodynia, disability grade, interictal burden, and anxiety and depression scores. For example, 47.3% of the HFEM subgroup and 54.9% of the LFCM subgroup had Patient Health Questionnaire–9 depression test scores greater than 10.

The study also evaluated patterns of consultation, diagnosis, and health resource utilization and found similar rates between the HFEM and LCFM subgroups, Dr. Lipton said. Rates of overnight hospital stay in the past 6 months were almost identical between the two subgroups: 4.1% for the former and 4.2% for the latter. One striking difference between the two subgroups: the rate of medication overuse per ICHD-3 recommendations was 40.5% in HFEM and 63% in LFCM.

“These finding suggest that the treatment needs of people with HFEM may be similar to those of people with LFCM, suggesting that the 15-MHD threshold currently recommended by the ICHD-3 may merit reconsideration,” Dr. Lipton said.
 

An arbitrary cutoff?

The findings raise a valid point about reevaluating the thresholds for low- and high-frequency migraine, said Andrew Charles, MD, director of the Goldberg Migraine Program at the University of California, Los Angeles. “My own personal view is that they’re the same thing,” he said of HFEM and LFCM; The 15-day cutoff, he said, is “somewhat arbitrary.”

Dr. Charles suggested migraine categories address frequency and not characteristics – episodic versus chronic – and use a range rather than a threshold. “Define a range that’s more like 10-20 days per month rather than having that point at 15,” Dr. Charles said. “People sometimes make the mistake of thinking that that classification reflects some underlying pathophysiology, and that may not be necessarily true.”

Dr. Lipton disclosed financial relationships with Alder Biopharmaceuticals, Allergan (now AbbVie), Amgen, Biohaven Pharmaceuticals, Dr. Reddy’s/Promius, Electrocore, Eli Lilly, eNeura Therapeutics, GlaxoSmithKline, Lundbeck (Alder), Merck, Pernix Therapeutics, Pfizer, Supernus, Teva, Trigemina, Axsome Therapeutics, Vector, and Vedanta. Dr. Charles disclosed he is a consultant to Amgen, Biohaven Pharmaceuticals, Eli Lilly, Lundbeck, and Novartis.

People with high-frequency episodic migraine and low-frequency chronic migraine may have similar treatment needs because characteristics of the two disorders overlap significantly, calling into question the existing threshold of 15 migraine headache days per month to distinguish low- and high-frequency migraine, according to an analysis of almost 17,000 patients from the Chronic Migraine Epidemiology and Outcomes (CaMEO) study presented at the virtual annual meeting of the American Headache Society.

“The results showed substantial overlap in levels of burden, anxiety, depression and health utilization, including outpatient, inpatient and emergency department visits, among CaMEO respondents with high-frequency episodic migraine and those with low-frequency chronic migraine,” said Richard B. Lipton, MD, of the Albert Einstein College of Medicine, New York.

The study analyzed data on 16,789 respondents to CaMEO, the longitudinal, web-based study designed to characterize the course of episodic and chronic migraine. The study population consisted of four subgroups based on the number of self-reporting monthly headache days (MHDs):

• Low- and moderate-frequency episodic migraine (LFEM; zero to seven MHDs; n = 13,473).
• High-frequency episodic migraine (HFEM; 8-14 MHDs; n = 1,840).
• Low-frequency chronic migraine (LFCM; 15-23 MHDs; n = 1,035).
• High-frequency chronic migraine (HFCM; 24 or more MHDs; n = 441).

Dr. Lipton pointed out that the International Classification of Headache Disorders, 3rd edition, defines chronic migraine as 15 or more MHDs for 3 months or more with criteria for migraine with or without aura met on 8 days a month or more. It defines episodic migraine as less than 15 MHDs.

The study characterized migraine subgroups by various demographics. “The more frequent headache categories were associated with slightly older age of onset with a higher proportion of BMI [body mass index] in the obese range and overall with lower levels of household income and education,” Dr. Lipton said.
 

Similar headache characteristics

A comparison of headache characteristics and headache-related disabilities across subgroups revealed a number of commonalities between the HFEM and LFCM subgroups, Dr. Lipton said. Among them were presence of mild to severe allodynia, disability grade, interictal burden, and anxiety and depression scores. For example, 47.3% of the HFEM subgroup and 54.9% of the LFCM subgroup had Patient Health Questionnaire–9 depression test scores greater than 10.

The study also evaluated patterns of consultation, diagnosis, and health resource utilization and found similar rates between the HFEM and LCFM subgroups, Dr. Lipton said. Rates of overnight hospital stay in the past 6 months were almost identical between the two subgroups: 4.1% for the former and 4.2% for the latter. One striking difference between the two subgroups: the rate of medication overuse per ICHD-3 recommendations was 40.5% in HFEM and 63% in LFCM.

“These finding suggest that the treatment needs of people with HFEM may be similar to those of people with LFCM, suggesting that the 15-MHD threshold currently recommended by the ICHD-3 may merit reconsideration,” Dr. Lipton said.
 

An arbitrary cutoff?

The findings raise a valid point about reevaluating the thresholds for low- and high-frequency migraine, said Andrew Charles, MD, director of the Goldberg Migraine Program at the University of California, Los Angeles. “My own personal view is that they’re the same thing,” he said of HFEM and LFCM; The 15-day cutoff, he said, is “somewhat arbitrary.”

Dr. Charles suggested migraine categories address frequency and not characteristics – episodic versus chronic – and use a range rather than a threshold. “Define a range that’s more like 10-20 days per month rather than having that point at 15,” Dr. Charles said. “People sometimes make the mistake of thinking that that classification reflects some underlying pathophysiology, and that may not be necessarily true.”

Dr. Lipton disclosed financial relationships with Alder Biopharmaceuticals, Allergan (now AbbVie), Amgen, Biohaven Pharmaceuticals, Dr. Reddy’s/Promius, Electrocore, Eli Lilly, eNeura Therapeutics, GlaxoSmithKline, Lundbeck (Alder), Merck, Pernix Therapeutics, Pfizer, Supernus, Teva, Trigemina, Axsome Therapeutics, Vector, and Vedanta. Dr. Charles disclosed he is a consultant to Amgen, Biohaven Pharmaceuticals, Eli Lilly, Lundbeck, and Novartis.

The calcitonin gene–related peptide receptor monoclonal antibodies (CGRP mAbs)for treatment of migraine have gained wide acceptance since their approval in 2018, but a real-world study has reported adverse event rates higher than those the preapproval clinical trials reported and has found that patients who fail on one of the treatments are likely to fail again if they’re switched to another.

At the virtual annual meeting of the American Headache Society, Larry Robbins, MD, assistant professor of neurology at Chicago Medical School, North Chicago, reported on the results of his postapproval study of 369 migraine patients taking one of the three approved CGRP mAbs. “If patients do not do well on one mAb, it is sometimes worthwhile to switch, but most patients do not do well from the second or third mAb as well,” Dr. Robbins said in an interview. “In addition, there are numerous adverse effects that were not captured in the official phase 3 studies. Efficacy has held up well, but for a number of reasons, the true adverse event profile is often missed.”
 

Assessing efficacy and adverse events

In evaluating the efficacy of the three approved CGRP mAbs, Dr. Robbins used measures of degree of relief based on percentage decrease of symptoms versus baseline and the number of migraine days, combined with the number of moderate or severe headache days. Most of the patients kept calendars and were interviewed by two headache specialists. The study also utilized a 10-point visual analog scale and averaged relief over 3 months.

Of the patients on erenumab (n = 220), 10% described 95%-100% relief of symptoms, 24% reported 71%-100% relief, 34% described 31%-70% relief, and 43% experienced 0%-30% relief. Adverse events among this group included constipation (20%), nausea (7%), increased headache and fatigue (5% for each), and joint pain and depression (3% for each). Three patients on erenumab experienced unspecified serious adverse reactions.

In the fremanezumab group (n = 79), 8% described 95%-100% relief, 18% had 71%-100% relief, 33% experienced 31%-70% improvement, and 50% had 30% improvement or less. Adverse events in these patients included nausea, constipation, and depression (6% each); increased headache and muscle pain or cramps (5% each); rash, joint pain, anxiety, fatigue, or weight gain (4% for each ); and injection-site reactions, irritability, or alopecia (3% combined).

Patients taking galcanezumab (n = 70) reported the following outcomes: 3% had 95%-100% relief of symptoms, 14% had 71%-100% relief, 46% with 31%-70% relief, and 40% had 0%-30% relief. This group’s adverse events included constipation (10%); depression and increased headache (6% for each); nausea, fatigue, or injection-site reactions (4% each ); and muscle pain or cramps, rash, anxiety, weight gain, or alopecia (3% each).

Dr. Robbins also assessed switching from one CGRP mAb to another for various reasons. “When the reason for switching was poor efficacy, only 27% of patients did well,” he stated in the presentation. “If the reason was adverse events, 33% did well. When insurance/financial reasons alone were the reason, but efficacy was adequate, 58% did well after switching.”

Overall, postapproval efficacy of the medications “held up well,” Dr. Robbins noted. “Efficacy after 2 months somewhat predicted how patients would do after 6 months.” Among the predictors of poor response his study identified were opioid use and moderate or severe refractory chronic migraine at baseline.

However, the rates of adverse events he reported were significantly greater than those reported in the clinical trials, Dr. Robbins said. He noted four reasons to explain this discrepancy: the trials did not use an 18-item supplemental checklist that he has advocated to identify patients at risk of side effects, the trials weren’t powered for adverse events, patients in the trials tended to be less refractory than those in the clinic, and that adverse events tend to be underreported in trials.

“Adverse events become disaggregated, with the same descriptors used for an adverse event,” Dr. Robbins said. “Examples include fatigue, somnolence, and tiredness; all may be 1%, while different patients are describing the same adverse event. It is possible to reaggregate the adverse events after the study, but this is fraught with error.”
 

Uncovering shortcomings in clinical trials

Emily Rubenstein Engel, MD, director of the Dalessio Headache Center at the Scripps Clinic in La Jolla, Calif., noted that Dr. Robbins’ findings are significant for two reasons. “Dr. Robbins has uncovered a general flaw in clinical trials, whereby the lack of consistency of adverse event terminology as well as the lack of a standardized questionnaire format for adverse events can result in significant under-reporting of adverse events,” she said.

“Specifically for the CGRPs,” Dr. Engel continued, “he has raised awareness that this new class of medication, however promising from an efficacy standpoint, has side effects that are much more frequent and severe than seen in the initial clinical trials.”

Dr. Robbins reported financial relationships with Allergan, Amgen and Teva. Dr. Engel has no financial relationships to disclose.

The calcitonin gene–related peptide receptor monoclonal antibodies (CGRP mAbs)for treatment of migraine have gained wide acceptance since their approval in 2018, but a real-world study has reported adverse event rates higher than those the preapproval clinical trials reported and has found that patients who fail on one of the treatments are likely to fail again if they’re switched to another.

At the virtual annual meeting of the American Headache Society, Larry Robbins, MD, assistant professor of neurology at Chicago Medical School, North Chicago, reported on the results of his postapproval study of 369 migraine patients taking one of the three approved CGRP mAbs. “If patients do not do well on one mAb, it is sometimes worthwhile to switch, but most patients do not do well from the second or third mAb as well,” Dr. Robbins said in an interview. “In addition, there are numerous adverse effects that were not captured in the official phase 3 studies. Efficacy has held up well, but for a number of reasons, the true adverse event profile is often missed.”
 

Assessing efficacy and adverse events

In evaluating the efficacy of the three approved CGRP mAbs, Dr. Robbins used measures of degree of relief based on percentage decrease of symptoms versus baseline and the number of migraine days, combined with the number of moderate or severe headache days. Most of the patients kept calendars and were interviewed by two headache specialists. The study also utilized a 10-point visual analog scale and averaged relief over 3 months.

Of the patients on erenumab (n = 220), 10% described 95%-100% relief of symptoms, 24% reported 71%-100% relief, 34% described 31%-70% relief, and 43% experienced 0%-30% relief. Adverse events among this group included constipation (20%), nausea (7%), increased headache and fatigue (5% for each), and joint pain and depression (3% for each). Three patients on erenumab experienced unspecified serious adverse reactions.

In the fremanezumab group (n = 79), 8% described 95%-100% relief, 18% had 71%-100% relief, 33% experienced 31%-70% improvement, and 50% had 30% improvement or less. Adverse events in these patients included nausea, constipation, and depression (6% each); increased headache and muscle pain or cramps (5% each); rash, joint pain, anxiety, fatigue, or weight gain (4% for each ); and injection-site reactions, irritability, or alopecia (3% combined).

Patients taking galcanezumab (n = 70) reported the following outcomes: 3% had 95%-100% relief of symptoms, 14% had 71%-100% relief, 46% with 31%-70% relief, and 40% had 0%-30% relief. This group’s adverse events included constipation (10%); depression and increased headache (6% for each); nausea, fatigue, or injection-site reactions (4% each ); and muscle pain or cramps, rash, anxiety, weight gain, or alopecia (3% each).

Dr. Robbins also assessed switching from one CGRP mAb to another for various reasons. “When the reason for switching was poor efficacy, only 27% of patients did well,” he stated in the presentation. “If the reason was adverse events, 33% did well. When insurance/financial reasons alone were the reason, but efficacy was adequate, 58% did well after switching.”

Overall, postapproval efficacy of the medications “held up well,” Dr. Robbins noted. “Efficacy after 2 months somewhat predicted how patients would do after 6 months.” Among the predictors of poor response his study identified were opioid use and moderate or severe refractory chronic migraine at baseline.

However, the rates of adverse events he reported were significantly greater than those reported in the clinical trials, Dr. Robbins said. He noted four reasons to explain this discrepancy: the trials did not use an 18-item supplemental checklist that he has advocated to identify patients at risk of side effects, the trials weren’t powered for adverse events, patients in the trials tended to be less refractory than those in the clinic, and that adverse events tend to be underreported in trials.

“Adverse events become disaggregated, with the same descriptors used for an adverse event,” Dr. Robbins said. “Examples include fatigue, somnolence, and tiredness; all may be 1%, while different patients are describing the same adverse event. It is possible to reaggregate the adverse events after the study, but this is fraught with error.”
 

Uncovering shortcomings in clinical trials

Emily Rubenstein Engel, MD, director of the Dalessio Headache Center at the Scripps Clinic in La Jolla, Calif., noted that Dr. Robbins’ findings are significant for two reasons. “Dr. Robbins has uncovered a general flaw in clinical trials, whereby the lack of consistency of adverse event terminology as well as the lack of a standardized questionnaire format for adverse events can result in significant under-reporting of adverse events,” she said.

“Specifically for the CGRPs,” Dr. Engel continued, “he has raised awareness that this new class of medication, however promising from an efficacy standpoint, has side effects that are much more frequent and severe than seen in the initial clinical trials.”

Dr. Robbins reported financial relationships with Allergan, Amgen and Teva. Dr. Engel has no financial relationships to disclose.

The calcitonin gene–related peptide receptor monoclonal antibodies (CGRP mAbs)for treatment of migraine have gained wide acceptance since their approval in 2018, but a real-world study has reported adverse event rates higher than those the preapproval clinical trials reported and has found that patients who fail on one of the treatments are likely to fail again if they’re switched to another.

At the virtual annual meeting of the American Headache Society, Larry Robbins, MD, assistant professor of neurology at Chicago Medical School, North Chicago, reported on the results of his postapproval study of 369 migraine patients taking one of the three approved CGRP mAbs. “If patients do not do well on one mAb, it is sometimes worthwhile to switch, but most patients do not do well from the second or third mAb as well,” Dr. Robbins said in an interview. “In addition, there are numerous adverse effects that were not captured in the official phase 3 studies. Efficacy has held up well, but for a number of reasons, the true adverse event profile is often missed.”
 

Assessing efficacy and adverse events

In evaluating the efficacy of the three approved CGRP mAbs, Dr. Robbins used measures of degree of relief based on percentage decrease of symptoms versus baseline and the number of migraine days, combined with the number of moderate or severe headache days. Most of the patients kept calendars and were interviewed by two headache specialists. The study also utilized a 10-point visual analog scale and averaged relief over 3 months.

Of the patients on erenumab (n = 220), 10% described 95%-100% relief of symptoms, 24% reported 71%-100% relief, 34% described 31%-70% relief, and 43% experienced 0%-30% relief. Adverse events among this group included constipation (20%), nausea (7%), increased headache and fatigue (5% for each), and joint pain and depression (3% for each). Three patients on erenumab experienced unspecified serious adverse reactions.

In the fremanezumab group (n = 79), 8% described 95%-100% relief, 18% had 71%-100% relief, 33% experienced 31%-70% improvement, and 50% had 30% improvement or less. Adverse events in these patients included nausea, constipation, and depression (6% each); increased headache and muscle pain or cramps (5% each); rash, joint pain, anxiety, fatigue, or weight gain (4% for each ); and injection-site reactions, irritability, or alopecia (3% combined).

Patients taking galcanezumab (n = 70) reported the following outcomes: 3% had 95%-100% relief of symptoms, 14% had 71%-100% relief, 46% with 31%-70% relief, and 40% had 0%-30% relief. This group’s adverse events included constipation (10%); depression and increased headache (6% for each); nausea, fatigue, or injection-site reactions (4% each ); and muscle pain or cramps, rash, anxiety, weight gain, or alopecia (3% each).

Dr. Robbins also assessed switching from one CGRP mAb to another for various reasons. “When the reason for switching was poor efficacy, only 27% of patients did well,” he stated in the presentation. “If the reason was adverse events, 33% did well. When insurance/financial reasons alone were the reason, but efficacy was adequate, 58% did well after switching.”

Overall, postapproval efficacy of the medications “held up well,” Dr. Robbins noted. “Efficacy after 2 months somewhat predicted how patients would do after 6 months.” Among the predictors of poor response his study identified were opioid use and moderate or severe refractory chronic migraine at baseline.

However, the rates of adverse events he reported were significantly greater than those reported in the clinical trials, Dr. Robbins said. He noted four reasons to explain this discrepancy: the trials did not use an 18-item supplemental checklist that he has advocated to identify patients at risk of side effects, the trials weren’t powered for adverse events, patients in the trials tended to be less refractory than those in the clinic, and that adverse events tend to be underreported in trials.

“Adverse events become disaggregated, with the same descriptors used for an adverse event,” Dr. Robbins said. “Examples include fatigue, somnolence, and tiredness; all may be 1%, while different patients are describing the same adverse event. It is possible to reaggregate the adverse events after the study, but this is fraught with error.”
 

Uncovering shortcomings in clinical trials

Emily Rubenstein Engel, MD, director of the Dalessio Headache Center at the Scripps Clinic in La Jolla, Calif., noted that Dr. Robbins’ findings are significant for two reasons. “Dr. Robbins has uncovered a general flaw in clinical trials, whereby the lack of consistency of adverse event terminology as well as the lack of a standardized questionnaire format for adverse events can result in significant under-reporting of adverse events,” she said.

“Specifically for the CGRPs,” Dr. Engel continued, “he has raised awareness that this new class of medication, however promising from an efficacy standpoint, has side effects that are much more frequent and severe than seen in the initial clinical trials.”

Dr. Robbins reported financial relationships with Allergan, Amgen and Teva. Dr. Engel has no financial relationships to disclose.

Preliminary results from a population-based cohort study support previous reports that migraine is a midlife risk factor for dementia later in life, but further determined that migraine with aura and frequent hospital contacts significantly increased dementia risk after age 60 years, according to results from a Danish registry presented at the virtual annual meeting of the American Headache Society.

“The findings of this study emphasize the need for studies in the migraine-dementia pathophysiology, in particular in migraine cases with aura,” said Sabrina Islamoska, MSc, PhD, a postdoctoral researcher in the department of public health at the University of Copenhagen. “This study highlights the importance of monitoring severe migraine to potentially prevent dementia.”
 

A national register-based study

The study used Danish national register–based data from 1988 to 2017 of 1.66 million individuals born between 1935 and 1956, retrieving exposure information until age 59 years and following individuals for dementia after age 60. The matched analysis included 18,135 people registered with migraine before age 59 and 1.38 million without migraine. The matched study population was 62,578.

A diagnosis of dementia or use of dementia medications after age 60 years was the main outcome. Covariates included socioeconomic factors, psychiatric comorbidities and other headache diagnoses.

“To the best of our knowledge, no previous national register–based studies have investigated the risk of dementia among individuals who suffer from migraine with aura,” Dr. Islamoska said.

The preliminary findings revealed that the median age at diagnosis was 49 years and about 70% of the migraine population were women. “There was a 50% higher dementia rate in individuals who had any migraine diagnosis,” Dr. Islamoska said.

“We also found a 20% higher but nonsignificant dementia rate in individuals who had migraine without aura,” she said. However, when the migraine-with-aura population was evaluated, it was found to have a dementia rate two times higher than people with no migraine. “The dementia rate was higher if individuals had more frequent hospital contacts with migraine.”

The findings support the hypothesis that migraine is a midlife risk factor for dementia later in life, she said.

“The findings underline the value of investigating the effect of migraine medications in dementia risk to assess the impact of mild to moderate migraines,” Dr. Islamoska said. “Therefore, the next step is to investigate the risk of dementia among users of migraine medications who are not diagnosed with migraines at hospitals.”

Strengths of the study, Dr. Islamoska noted, were its size and national nature of its population, that it included all migraine diagnoses at hospitals over a 29-year period, that it made adjustments for confounding of well-established dementia risk factors, and that it validated dementia diagnoses after age 60 years.

One limitation was that the study only included hospital-based diagnoses of dementia while 60% of cases in Denmark are undiagnosed, “thus our results only apply to migraine that is severe enough to require a hospital contact,” Dr. Islamoska said, while most migraine cases are treated in the primary care setting.

Also, the young study population may have a lower dementia risk. “We also know that age of migraine registration may not corresponded with the actual onset, since migraine is a complex disorder with individual variation in patient’s burden and course of disease,” Dr. Islamoska said.

“Future studies are needed to understand the pathological mechanisms underlying the relationship between migraine and dementia and to investigate whether proper prophylactic treatment of migraine can potentially prevent dementia,” Dr. Islamoska said. “In addition, when investigating the association between these two prevalent neurological disorders, the timing of migraine diagnosis and dementia onset is important to ensure temporality. We took this into account in our study to strengthen the validity of our results.”
 

‘Surprising’ findings

Andrew Charles, MD, director of the Goldberg Migraine Program at the University of California, Los Angeles, said the Danish study makes an important contribution to the literature on dementia risk factors. “Vanishingly small amounts of attention have been paid to migraine as a potential risk factor,” he said. However, he called the results “surprising” based on his own clinical experience. “I actually had a sense that migraine was somehow protective against Alzheimer’s or other kinds of dementias.”

He questioned if the migraine-dementia link could be a “reporting artifact” of migraine sufferers merely going to the neurologist, raising the likelihood of a positive migraine diagnosis. Nonetheless, the results are “intriguing” and raise important questions about migraine therapy and dementia risk.

“If it holds up, it really is something that behooves us to understand whether intervening in terms of therapy for migraine has even more consequences beyond just the immediate relief of symptoms,” Dr. Charles said. “It’s something we should be thinking about in terms of preventing longer-term consequences of this disorder.”

Dr. Islamoska disclosed that Veluxfondent funded the study as part of her PhD project. Dr. Charles disclosed he is a consultant to Amgen, Biohaven Pharmaceuticals, Eli Lilly, Lundbeck, and Novartis.

SOURCE: Islamoska S et al. AHS 2020, Submission 846214.

Preliminary results from a population-based cohort study support previous reports that migraine is a midlife risk factor for dementia later in life, but further determined that migraine with aura and frequent hospital contacts significantly increased dementia risk after age 60 years, according to results from a Danish registry presented at the virtual annual meeting of the American Headache Society.

“The findings of this study emphasize the need for studies in the migraine-dementia pathophysiology, in particular in migraine cases with aura,” said Sabrina Islamoska, MSc, PhD, a postdoctoral researcher in the department of public health at the University of Copenhagen. “This study highlights the importance of monitoring severe migraine to potentially prevent dementia.”
 

A national register-based study

The study used Danish national register–based data from 1988 to 2017 of 1.66 million individuals born between 1935 and 1956, retrieving exposure information until age 59 years and following individuals for dementia after age 60. The matched analysis included 18,135 people registered with migraine before age 59 and 1.38 million without migraine. The matched study population was 62,578.

A diagnosis of dementia or use of dementia medications after age 60 years was the main outcome. Covariates included socioeconomic factors, psychiatric comorbidities and other headache diagnoses.

“To the best of our knowledge, no previous national register–based studies have investigated the risk of dementia among individuals who suffer from migraine with aura,” Dr. Islamoska said.

The preliminary findings revealed that the median age at diagnosis was 49 years and about 70% of the migraine population were women. “There was a 50% higher dementia rate in individuals who had any migraine diagnosis,” Dr. Islamoska said.

“We also found a 20% higher but nonsignificant dementia rate in individuals who had migraine without aura,” she said. However, when the migraine-with-aura population was evaluated, it was found to have a dementia rate two times higher than people with no migraine. “The dementia rate was higher if individuals had more frequent hospital contacts with migraine.”

The findings support the hypothesis that migraine is a midlife risk factor for dementia later in life, she said.

“The findings underline the value of investigating the effect of migraine medications in dementia risk to assess the impact of mild to moderate migraines,” Dr. Islamoska said. “Therefore, the next step is to investigate the risk of dementia among users of migraine medications who are not diagnosed with migraines at hospitals.”

Strengths of the study, Dr. Islamoska noted, were its size and national nature of its population, that it included all migraine diagnoses at hospitals over a 29-year period, that it made adjustments for confounding of well-established dementia risk factors, and that it validated dementia diagnoses after age 60 years.

One limitation was that the study only included hospital-based diagnoses of dementia while 60% of cases in Denmark are undiagnosed, “thus our results only apply to migraine that is severe enough to require a hospital contact,” Dr. Islamoska said, while most migraine cases are treated in the primary care setting.

Also, the young study population may have a lower dementia risk. “We also know that age of migraine registration may not corresponded with the actual onset, since migraine is a complex disorder with individual variation in patient’s burden and course of disease,” Dr. Islamoska said.

“Future studies are needed to understand the pathological mechanisms underlying the relationship between migraine and dementia and to investigate whether proper prophylactic treatment of migraine can potentially prevent dementia,” Dr. Islamoska said. “In addition, when investigating the association between these two prevalent neurological disorders, the timing of migraine diagnosis and dementia onset is important to ensure temporality. We took this into account in our study to strengthen the validity of our results.”
 

‘Surprising’ findings

Andrew Charles, MD, director of the Goldberg Migraine Program at the University of California, Los Angeles, said the Danish study makes an important contribution to the literature on dementia risk factors. “Vanishingly small amounts of attention have been paid to migraine as a potential risk factor,” he said. However, he called the results “surprising” based on his own clinical experience. “I actually had a sense that migraine was somehow protective against Alzheimer’s or other kinds of dementias.”

He questioned if the migraine-dementia link could be a “reporting artifact” of migraine sufferers merely going to the neurologist, raising the likelihood of a positive migraine diagnosis. Nonetheless, the results are “intriguing” and raise important questions about migraine therapy and dementia risk.

“If it holds up, it really is something that behooves us to understand whether intervening in terms of therapy for migraine has even more consequences beyond just the immediate relief of symptoms,” Dr. Charles said. “It’s something we should be thinking about in terms of preventing longer-term consequences of this disorder.”

Dr. Islamoska disclosed that Veluxfondent funded the study as part of her PhD project. Dr. Charles disclosed he is a consultant to Amgen, Biohaven Pharmaceuticals, Eli Lilly, Lundbeck, and Novartis.

SOURCE: Islamoska S et al. AHS 2020, Submission 846214.

Preliminary results from a population-based cohort study support previous reports that migraine is a midlife risk factor for dementia later in life, but further determined that migraine with aura and frequent hospital contacts significantly increased dementia risk after age 60 years, according to results from a Danish registry presented at the virtual annual meeting of the American Headache Society.

“The findings of this study emphasize the need for studies in the migraine-dementia pathophysiology, in particular in migraine cases with aura,” said Sabrina Islamoska, MSc, PhD, a postdoctoral researcher in the department of public health at the University of Copenhagen. “This study highlights the importance of monitoring severe migraine to potentially prevent dementia.”
 

A national register-based study

The study used Danish national register–based data from 1988 to 2017 of 1.66 million individuals born between 1935 and 1956, retrieving exposure information until age 59 years and following individuals for dementia after age 60. The matched analysis included 18,135 people registered with migraine before age 59 and 1.38 million without migraine. The matched study population was 62,578.

A diagnosis of dementia or use of dementia medications after age 60 years was the main outcome. Covariates included socioeconomic factors, psychiatric comorbidities and other headache diagnoses.

“To the best of our knowledge, no previous national register–based studies have investigated the risk of dementia among individuals who suffer from migraine with aura,” Dr. Islamoska said.

The preliminary findings revealed that the median age at diagnosis was 49 years and about 70% of the migraine population were women. “There was a 50% higher dementia rate in individuals who had any migraine diagnosis,” Dr. Islamoska said.

“We also found a 20% higher but nonsignificant dementia rate in individuals who had migraine without aura,” she said. However, when the migraine-with-aura population was evaluated, it was found to have a dementia rate two times higher than people with no migraine. “The dementia rate was higher if individuals had more frequent hospital contacts with migraine.”

The findings support the hypothesis that migraine is a midlife risk factor for dementia later in life, she said.

“The findings underline the value of investigating the effect of migraine medications in dementia risk to assess the impact of mild to moderate migraines,” Dr. Islamoska said. “Therefore, the next step is to investigate the risk of dementia among users of migraine medications who are not diagnosed with migraines at hospitals.”

Strengths of the study, Dr. Islamoska noted, were its size and national nature of its population, that it included all migraine diagnoses at hospitals over a 29-year period, that it made adjustments for confounding of well-established dementia risk factors, and that it validated dementia diagnoses after age 60 years.

One limitation was that the study only included hospital-based diagnoses of dementia while 60% of cases in Denmark are undiagnosed, “thus our results only apply to migraine that is severe enough to require a hospital contact,” Dr. Islamoska said, while most migraine cases are treated in the primary care setting.

Also, the young study population may have a lower dementia risk. “We also know that age of migraine registration may not corresponded with the actual onset, since migraine is a complex disorder with individual variation in patient’s burden and course of disease,” Dr. Islamoska said.

“Future studies are needed to understand the pathological mechanisms underlying the relationship between migraine and dementia and to investigate whether proper prophylactic treatment of migraine can potentially prevent dementia,” Dr. Islamoska said. “In addition, when investigating the association between these two prevalent neurological disorders, the timing of migraine diagnosis and dementia onset is important to ensure temporality. We took this into account in our study to strengthen the validity of our results.”
 

‘Surprising’ findings

Andrew Charles, MD, director of the Goldberg Migraine Program at the University of California, Los Angeles, said the Danish study makes an important contribution to the literature on dementia risk factors. “Vanishingly small amounts of attention have been paid to migraine as a potential risk factor,” he said. However, he called the results “surprising” based on his own clinical experience. “I actually had a sense that migraine was somehow protective against Alzheimer’s or other kinds of dementias.”

He questioned if the migraine-dementia link could be a “reporting artifact” of migraine sufferers merely going to the neurologist, raising the likelihood of a positive migraine diagnosis. Nonetheless, the results are “intriguing” and raise important questions about migraine therapy and dementia risk.

“If it holds up, it really is something that behooves us to understand whether intervening in terms of therapy for migraine has even more consequences beyond just the immediate relief of symptoms,” Dr. Charles said. “It’s something we should be thinking about in terms of preventing longer-term consequences of this disorder.”

Dr. Islamoska disclosed that Veluxfondent funded the study as part of her PhD project. Dr. Charles disclosed he is a consultant to Amgen, Biohaven Pharmaceuticals, Eli Lilly, Lundbeck, and Novartis.

SOURCE: Islamoska S et al. AHS 2020, Submission 846214.

Nausea, vomiting, and diarrhea are gastrointestinal symptoms that COVID-19 patients have had, and up to 30% have been reported to have liver symptoms. Because patients with these symptoms may require endoscopy, the American Gastroenterological Association has issued a rapid recommendation document that advises physicians and health care workers to use N95 masks, double gloves, and negative pressure rooms when performing GI procedures during the COVID-19 pandemic.

The recommendations, published in Gastroenterology (2020. doi: 10.1053/j.gastro.2020.03.072), also cover non-COVID-19 patients and situations where N95 masks should be used, offer guidelines for triaging patients for endoscopy and timing of nonurgent procedures, and evaluate the latest evidence in the incidence of GI and liver manifestations of COVID-19. The guideline panel met in March.

The document includes seven recommendations for use of personal protective equipment by physicians and nurses performing GI procedures. The recommendations and the level of evidence supporting them fall under four categories:

1. Masks, comprising four recommendations: N95 masks for upper and lower GI procedures regardless of a patient’s COVID-19 status; no surgical masks only in confirmed COVID-19 patients or suspected cases; and reused N95 masks when fresh ones aren’t available instead of using a surgical mask only (very low to moderate level of evidence depending on the recommendation).

2. Double-gloving when performing any GI procedure regardless of the patient’s COVID-19 status (moderate quality evidence).

3. When available, a negative-pressure room should be used for any COVID-19 patient or suspect rather than a regular endoscopy room (very low certainty of evidence).

4. Continue to practice standard cleaning, endoscopic disinfection, and reprocessing protocols regardless of a patient’s COVID-19 status (good practice statement).

For decontamination, the panel noted that commonly used biocidal agents, such as hydrogen peroxide, alcohols, sodium hypochlorite, or benzalkonium chloride have proved effective for decontaminating of coronavirus.

For implementing the PPE recommendations, the panel stated that personnel still need to practice don and doff standard protocols, and that N95 masks should be fitted for each individual.

Other steps include banning personal belongings in the procedure area, minimizing the number of personnel in the room, avoiding change of personnel and keeping nonprocedural personnel out during the procedure, considering using nursing teams that follow the patient through preprocedure, procedure, and recovery, and considering having endoscopy teams remain together during the day to minimize exposure.

The triage recommendations stated that “trained medical personnel” should review all procedures and categorize them as time-sensitive or not time-sensitive, based on a framework the recommendation includes. In “an open-access endoscopy system” when there isn’t enough information to determine timing for the procedure, the recommendation provides a three-step approach: a phone consult with the referring physician, a telehealth visit with the patient, or a multidisciplinary team approach or virtual disease/tumor board.

“The proposed framework of separating procedures into time-sensitive and non–time-sensitive cases may be useful in determining which procedures if delayed may negatively impact on patient-important outcomes,” wrote Shahnaz Sultan, MD, AGAF, of the University of Minnesota, Minneapolis, and colleagues. The panel noted decision-making should focus on “patient-important outcomes.”

For nonurgent procedures, the panel arrived at a consensus that 8 weeks was an appropriate window for reassessment of deferred procedures, depending on the availability of resources and if the time sensitivity of the procedure changes.

The panel also attempted to determine the likelihood of GI and liver manifestations of COVID-19 by evaluating published cohort studies. They found that 2%-13.8% of patients had diarrhea, 1%-10.1% had nausea or vomiting, and one study reported 2% had abdominal pain (Am J Gastroenterol. 2020 May;115[5]766-73). What’s more, some studies have shown stool samples positive for SARS-CoV-2 RNA even after respiratory samples were negative.

The evidence on liver manifestations isn’t as robust, but one study reported that 20%-30% of patients had liver injury upon diagnosis of COVID-19 (Gastroenterology. 2020;158:1518-9), and that severe hepatitis has been reported but liver failure seems rare (Lancet. 2020 Feb 15;395[10223]:507-13). “The pattern of liver injury appears to be predominantly hepatocellular, and the etiology remains uncertain but may represent a secondary effect of the systemic inflammatory response observed with COVID-19 disease, although direct viral infection and drug-induced liver injury cannot be excluded,” Dr. Sultan and colleagues noted.

There were no relevant author conflicts of interest. The American Gastroenterological Association (AGA) Institute funded the study.

SOURCE: Sultan S et al. Gastroenterology. 2020. doi: 10.1053/j.gastro.2020.03.072.

Nausea, vomiting, and diarrhea are gastrointestinal symptoms that COVID-19 patients have had, and up to 30% have been reported to have liver symptoms. Because patients with these symptoms may require endoscopy, the American Gastroenterological Association has issued a rapid recommendation document that advises physicians and health care workers to use N95 masks, double gloves, and negative pressure rooms when performing GI procedures during the COVID-19 pandemic.

The recommendations, published in Gastroenterology (2020. doi: 10.1053/j.gastro.2020.03.072), also cover non-COVID-19 patients and situations where N95 masks should be used, offer guidelines for triaging patients for endoscopy and timing of nonurgent procedures, and evaluate the latest evidence in the incidence of GI and liver manifestations of COVID-19. The guideline panel met in March.

The document includes seven recommendations for use of personal protective equipment by physicians and nurses performing GI procedures. The recommendations and the level of evidence supporting them fall under four categories:

1. Masks, comprising four recommendations: N95 masks for upper and lower GI procedures regardless of a patient’s COVID-19 status; no surgical masks only in confirmed COVID-19 patients or suspected cases; and reused N95 masks when fresh ones aren’t available instead of using a surgical mask only (very low to moderate level of evidence depending on the recommendation).

2. Double-gloving when performing any GI procedure regardless of the patient’s COVID-19 status (moderate quality evidence).

3. When available, a negative-pressure room should be used for any COVID-19 patient or suspect rather than a regular endoscopy room (very low certainty of evidence).

4. Continue to practice standard cleaning, endoscopic disinfection, and reprocessing protocols regardless of a patient’s COVID-19 status (good practice statement).

For decontamination, the panel noted that commonly used biocidal agents, such as hydrogen peroxide, alcohols, sodium hypochlorite, or benzalkonium chloride have proved effective for decontaminating of coronavirus.

For implementing the PPE recommendations, the panel stated that personnel still need to practice don and doff standard protocols, and that N95 masks should be fitted for each individual.

Other steps include banning personal belongings in the procedure area, minimizing the number of personnel in the room, avoiding change of personnel and keeping nonprocedural personnel out during the procedure, considering using nursing teams that follow the patient through preprocedure, procedure, and recovery, and considering having endoscopy teams remain together during the day to minimize exposure.

The triage recommendations stated that “trained medical personnel” should review all procedures and categorize them as time-sensitive or not time-sensitive, based on a framework the recommendation includes. In “an open-access endoscopy system” when there isn’t enough information to determine timing for the procedure, the recommendation provides a three-step approach: a phone consult with the referring physician, a telehealth visit with the patient, or a multidisciplinary team approach or virtual disease/tumor board.

“The proposed framework of separating procedures into time-sensitive and non–time-sensitive cases may be useful in determining which procedures if delayed may negatively impact on patient-important outcomes,” wrote Shahnaz Sultan, MD, AGAF, of the University of Minnesota, Minneapolis, and colleagues. The panel noted decision-making should focus on “patient-important outcomes.”

For nonurgent procedures, the panel arrived at a consensus that 8 weeks was an appropriate window for reassessment of deferred procedures, depending on the availability of resources and if the time sensitivity of the procedure changes.

The panel also attempted to determine the likelihood of GI and liver manifestations of COVID-19 by evaluating published cohort studies. They found that 2%-13.8% of patients had diarrhea, 1%-10.1% had nausea or vomiting, and one study reported 2% had abdominal pain (Am J Gastroenterol. 2020 May;115[5]766-73). What’s more, some studies have shown stool samples positive for SARS-CoV-2 RNA even after respiratory samples were negative.

The evidence on liver manifestations isn’t as robust, but one study reported that 20%-30% of patients had liver injury upon diagnosis of COVID-19 (Gastroenterology. 2020;158:1518-9), and that severe hepatitis has been reported but liver failure seems rare (Lancet. 2020 Feb 15;395[10223]:507-13). “The pattern of liver injury appears to be predominantly hepatocellular, and the etiology remains uncertain but may represent a secondary effect of the systemic inflammatory response observed with COVID-19 disease, although direct viral infection and drug-induced liver injury cannot be excluded,” Dr. Sultan and colleagues noted.

There were no relevant author conflicts of interest. The American Gastroenterological Association (AGA) Institute funded the study.

SOURCE: Sultan S et al. Gastroenterology. 2020. doi: 10.1053/j.gastro.2020.03.072.

Nausea, vomiting, and diarrhea are gastrointestinal symptoms that COVID-19 patients have had, and up to 30% have been reported to have liver symptoms. Because patients with these symptoms may require endoscopy, the American Gastroenterological Association has issued a rapid recommendation document that advises physicians and health care workers to use N95 masks, double gloves, and negative pressure rooms when performing GI procedures during the COVID-19 pandemic.

The recommendations, published in Gastroenterology (2020. doi: 10.1053/j.gastro.2020.03.072), also cover non-COVID-19 patients and situations where N95 masks should be used, offer guidelines for triaging patients for endoscopy and timing of nonurgent procedures, and evaluate the latest evidence in the incidence of GI and liver manifestations of COVID-19. The guideline panel met in March.

The document includes seven recommendations for use of personal protective equipment by physicians and nurses performing GI procedures. The recommendations and the level of evidence supporting them fall under four categories:

1. Masks, comprising four recommendations: N95 masks for upper and lower GI procedures regardless of a patient’s COVID-19 status; no surgical masks only in confirmed COVID-19 patients or suspected cases; and reused N95 masks when fresh ones aren’t available instead of using a surgical mask only (very low to moderate level of evidence depending on the recommendation).

2. Double-gloving when performing any GI procedure regardless of the patient’s COVID-19 status (moderate quality evidence).

3. When available, a negative-pressure room should be used for any COVID-19 patient or suspect rather than a regular endoscopy room (very low certainty of evidence).

4. Continue to practice standard cleaning, endoscopic disinfection, and reprocessing protocols regardless of a patient’s COVID-19 status (good practice statement).

For decontamination, the panel noted that commonly used biocidal agents, such as hydrogen peroxide, alcohols, sodium hypochlorite, or benzalkonium chloride have proved effective for decontaminating of coronavirus.

For implementing the PPE recommendations, the panel stated that personnel still need to practice don and doff standard protocols, and that N95 masks should be fitted for each individual.

Other steps include banning personal belongings in the procedure area, minimizing the number of personnel in the room, avoiding change of personnel and keeping nonprocedural personnel out during the procedure, considering using nursing teams that follow the patient through preprocedure, procedure, and recovery, and considering having endoscopy teams remain together during the day to minimize exposure.

The triage recommendations stated that “trained medical personnel” should review all procedures and categorize them as time-sensitive or not time-sensitive, based on a framework the recommendation includes. In “an open-access endoscopy system” when there isn’t enough information to determine timing for the procedure, the recommendation provides a three-step approach: a phone consult with the referring physician, a telehealth visit with the patient, or a multidisciplinary team approach or virtual disease/tumor board.

“The proposed framework of separating procedures into time-sensitive and non–time-sensitive cases may be useful in determining which procedures if delayed may negatively impact on patient-important outcomes,” wrote Shahnaz Sultan, MD, AGAF, of the University of Minnesota, Minneapolis, and colleagues. The panel noted decision-making should focus on “patient-important outcomes.”

For nonurgent procedures, the panel arrived at a consensus that 8 weeks was an appropriate window for reassessment of deferred procedures, depending on the availability of resources and if the time sensitivity of the procedure changes.

The panel also attempted to determine the likelihood of GI and liver manifestations of COVID-19 by evaluating published cohort studies. They found that 2%-13.8% of patients had diarrhea, 1%-10.1% had nausea or vomiting, and one study reported 2% had abdominal pain (Am J Gastroenterol. 2020 May;115[5]766-73). What’s more, some studies have shown stool samples positive for SARS-CoV-2 RNA even after respiratory samples were negative.

The evidence on liver manifestations isn’t as robust, but one study reported that 20%-30% of patients had liver injury upon diagnosis of COVID-19 (Gastroenterology. 2020;158:1518-9), and that severe hepatitis has been reported but liver failure seems rare (Lancet. 2020 Feb 15;395[10223]:507-13). “The pattern of liver injury appears to be predominantly hepatocellular, and the etiology remains uncertain but may represent a secondary effect of the systemic inflammatory response observed with COVID-19 disease, although direct viral infection and drug-induced liver injury cannot be excluded,” Dr. Sultan and colleagues noted.

There were no relevant author conflicts of interest. The American Gastroenterological Association (AGA) Institute funded the study.

SOURCE: Sultan S et al. Gastroenterology. 2020. doi: 10.1053/j.gastro.2020.03.072.

Inflammatory bowel disease (IBD) does not seem to make patients any more likely to contract SARS-COV-2 or develop COVID-19, but a rapid review commissioned by the American Gastroenterological Association acknowledges that determination is based on limited evidence and IBD patients should nonetheless maintain remission to reduce their risk of relapse or hospitalization during the COVID-19 pandemic.

The AGA has published a clinical practice update based on that rapid review online in Gastroenterology (2020. doi: 10.1053/j.gastro.2020.04.012).

Because of the widespread use of immunosuppressive or immune-modifying drugs, “It is understandable why patients with Crohn’s disease and ulcerative colitis have specific concerns and potential for increased risk of infection with SARS-CoV-2,” wrote David T. Rubin, MD, AGAF, of the University of Chicago and colleagues in the expert commentary.

They noted that, while association between GI symptoms and COVID-19 RNA in stool samples isn’t clear, given the reports of GI symptoms in COVID-19 patients – ranging from 10% (JAMA. 2020:323:1061-9) to half of patients (Am J Gastroenterol. 2020;115:766-73) – “the clinical implications of this are quite important.” In IBD patients, changes in digestive symptoms without accompanying fever or respiratory symptoms can be monitored for symptoms that could merit testing for the virus as well as “trigger additional treatment adjustments.”

In accordance with the IOIBD (International Organization for the Study of Inflammatory Bowel Disease) consensus, the update noted that IBD patients should continue going to infusion centers for therapies, provided that the centers use a COVID-19 screening protocol.

Patients with IBD who contract COVID-19 seem more likely to be hospitalized for one or the other disease, but that’s based on data from the international SECURE-IBD registry that had 164 patients as of the writing of the update. The update provides guidance for three scenarios for IBD patients during the pandemic:

• Patients not infected with SARS-CoV-2 should maintain their IBD therapies to sustain remission and avoid relapses. “Aside from the obvious negative consequences of a relapse, relapsing IBD will strain available medical resources, may require steroid therapy or necessitate hospitalization, outcomes that are all much worse than the known risks of existing IBD therapies,” Dr. Rubin and colleagues noted.
• Patients who are infected but have no symptoms of COVID-19 should have their dosing of prednisone adjusted to less than 20 mg/day or switched to budesonide; suspend thiopurines, methotrexate, and tofacitinib; and delay dosing of monoclonal antibodies (anti–tumor necrosis factor [anti-TNF] drugs, ustekinumab, or vedolizumab) for 2 weeks while their symptoms for COVID-19 are monitored. “Restarting therapy after 2 weeks if the patient has not developed manifestations of COVID-19 is reasonable,” wrote Dr. Rubin and colleagues. Emerging serial testing should indicate antibody status, but the effectiveness of stool testing for SARS-CoV-2 in these cases “remains to be seen.”
• In the patient with confirmed COVID-19, adjustment of IBD therapy “is appropriate, based on the understanding of the immune activity of the therapy and whether that therapy may worsen outcomes with COVID-19,” the update stated. Therapy adjustment should focus on reducing immune suppression during the active viral infection. Some studies are evaluating anticytokine-based therapies as COVID-19 treatments, so continued anti-TNF therapies might prevent acute respiratory distress syndrome and multiorgan failure, Dr. Rubin and colleagues wrote. “However, in the absence of those data, guidance is currently based on deciding whether to hold or to continue specific IBD therapies.”

The update considers most IBD therapies, specifically aminosalicylates, topical rectal therapy, dietary management, and antibiotics “safe and may be continued,” and oral budesonide can be continued if it’s needed for ongoing IBD control. However, corticosteroids “should be avoided and discontinued quickly.”

Likewise, during the acute stage of COVID-19, thiopurines, methotrexate, and tofacitinib should be discontinued, and anti-TNF drugs and ustekinumab should be stopped during viral illness. Holding vedolizumab during viral illness is also appropriate, according to the update, although the IOIBD group was uncertain if doing so was necessary.

If the IBD patient has digestive symptoms with COVID-19, ongoing supportive care of the COVID-19 is “reasonable,” but investigating the causes of the digestive symptoms “is critically important.” That should include ruling out enteric infections and confirming active inflammation with nonendoscopic testing. Endoscopy should be relegated to only urgent and emergent cases.

Management of IBD in COVID-19 patients also depends on disease severity. Safer therapies are indicated for mild disease, but withholding IBD therapy in moderate to severe cases may not be practical. “In this setting, the risks and benefits of escalating IBD therapy must be carefully weighed against the severity of the COVID-19,” Dr. Rubin and colleagues noted.

In hospitalized patients with severe COVID-19 and poor prognoses, “IBD therapy will likely take a back seat,” the update stated, although COVID-19 therapies should take the concomitant IBD into account. In patients with milder cases of COVID-19, IBD management should focus on acute manifestations, but intravenous steroid therapy shouldn’t exceed 3 days. The update urged providers to submit cases of IBD and confirmed COVID-19 to the SECURE-IBD registry at COVIDIBD.org.

Dr. Rubin disclosed financial relationships with AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene/Syneos, Gilead Sciences, Takeda, and many other pharmaceutical companies. Coauthors disclosed relationships with those companies and Medimmune, Novus Therapeutics, Osiris Therapeutics, RedHill Biopharma, Sanofi-Aventis, UCB Pharma, and multiple other pharmaceutical companies.

SOURCE: Rubin DT, et al. Gastroenterology. 2020:  doi: 10.1053/j.gastro.2020.04.012

Inflammatory bowel disease (IBD) does not seem to make patients any more likely to contract SARS-COV-2 or develop COVID-19, but a rapid review commissioned by the American Gastroenterological Association acknowledges that determination is based on limited evidence and IBD patients should nonetheless maintain remission to reduce their risk of relapse or hospitalization during the COVID-19 pandemic.

The AGA has published a clinical practice update based on that rapid review online in Gastroenterology (2020. doi: 10.1053/j.gastro.2020.04.012).

Because of the widespread use of immunosuppressive or immune-modifying drugs, “It is understandable why patients with Crohn’s disease and ulcerative colitis have specific concerns and potential for increased risk of infection with SARS-CoV-2,” wrote David T. Rubin, MD, AGAF, of the University of Chicago and colleagues in the expert commentary.

They noted that, while association between GI symptoms and COVID-19 RNA in stool samples isn’t clear, given the reports of GI symptoms in COVID-19 patients – ranging from 10% (JAMA. 2020:323:1061-9) to half of patients (Am J Gastroenterol. 2020;115:766-73) – “the clinical implications of this are quite important.” In IBD patients, changes in digestive symptoms without accompanying fever or respiratory symptoms can be monitored for symptoms that could merit testing for the virus as well as “trigger additional treatment adjustments.”

In accordance with the IOIBD (International Organization for the Study of Inflammatory Bowel Disease) consensus, the update noted that IBD patients should continue going to infusion centers for therapies, provided that the centers use a COVID-19 screening protocol.

Patients with IBD who contract COVID-19 seem more likely to be hospitalized for one or the other disease, but that’s based on data from the international SECURE-IBD registry that had 164 patients as of the writing of the update. The update provides guidance for three scenarios for IBD patients during the pandemic:

• Patients not infected with SARS-CoV-2 should maintain their IBD therapies to sustain remission and avoid relapses. “Aside from the obvious negative consequences of a relapse, relapsing IBD will strain available medical resources, may require steroid therapy or necessitate hospitalization, outcomes that are all much worse than the known risks of existing IBD therapies,” Dr. Rubin and colleagues noted.
• Patients who are infected but have no symptoms of COVID-19 should have their dosing of prednisone adjusted to less than 20 mg/day or switched to budesonide; suspend thiopurines, methotrexate, and tofacitinib; and delay dosing of monoclonal antibodies (anti–tumor necrosis factor [anti-TNF] drugs, ustekinumab, or vedolizumab) for 2 weeks while their symptoms for COVID-19 are monitored. “Restarting therapy after 2 weeks if the patient has not developed manifestations of COVID-19 is reasonable,” wrote Dr. Rubin and colleagues. Emerging serial testing should indicate antibody status, but the effectiveness of stool testing for SARS-CoV-2 in these cases “remains to be seen.”
• In the patient with confirmed COVID-19, adjustment of IBD therapy “is appropriate, based on the understanding of the immune activity of the therapy and whether that therapy may worsen outcomes with COVID-19,” the update stated. Therapy adjustment should focus on reducing immune suppression during the active viral infection. Some studies are evaluating anticytokine-based therapies as COVID-19 treatments, so continued anti-TNF therapies might prevent acute respiratory distress syndrome and multiorgan failure, Dr. Rubin and colleagues wrote. “However, in the absence of those data, guidance is currently based on deciding whether to hold or to continue specific IBD therapies.”

The update considers most IBD therapies, specifically aminosalicylates, topical rectal therapy, dietary management, and antibiotics “safe and may be continued,” and oral budesonide can be continued if it’s needed for ongoing IBD control. However, corticosteroids “should be avoided and discontinued quickly.”

Likewise, during the acute stage of COVID-19, thiopurines, methotrexate, and tofacitinib should be discontinued, and anti-TNF drugs and ustekinumab should be stopped during viral illness. Holding vedolizumab during viral illness is also appropriate, according to the update, although the IOIBD group was uncertain if doing so was necessary.

If the IBD patient has digestive symptoms with COVID-19, ongoing supportive care of the COVID-19 is “reasonable,” but investigating the causes of the digestive symptoms “is critically important.” That should include ruling out enteric infections and confirming active inflammation with nonendoscopic testing. Endoscopy should be relegated to only urgent and emergent cases.

Management of IBD in COVID-19 patients also depends on disease severity. Safer therapies are indicated for mild disease, but withholding IBD therapy in moderate to severe cases may not be practical. “In this setting, the risks and benefits of escalating IBD therapy must be carefully weighed against the severity of the COVID-19,” Dr. Rubin and colleagues noted.

In hospitalized patients with severe COVID-19 and poor prognoses, “IBD therapy will likely take a back seat,” the update stated, although COVID-19 therapies should take the concomitant IBD into account. In patients with milder cases of COVID-19, IBD management should focus on acute manifestations, but intravenous steroid therapy shouldn’t exceed 3 days. The update urged providers to submit cases of IBD and confirmed COVID-19 to the SECURE-IBD registry at COVIDIBD.org.

Dr. Rubin disclosed financial relationships with AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene/Syneos, Gilead Sciences, Takeda, and many other pharmaceutical companies. Coauthors disclosed relationships with those companies and Medimmune, Novus Therapeutics, Osiris Therapeutics, RedHill Biopharma, Sanofi-Aventis, UCB Pharma, and multiple other pharmaceutical companies.

SOURCE: Rubin DT, et al. Gastroenterology. 2020:  doi: 10.1053/j.gastro.2020.04.012

Inflammatory bowel disease (IBD) does not seem to make patients any more likely to contract SARS-COV-2 or develop COVID-19, but a rapid review commissioned by the American Gastroenterological Association acknowledges that determination is based on limited evidence and IBD patients should nonetheless maintain remission to reduce their risk of relapse or hospitalization during the COVID-19 pandemic.

The AGA has published a clinical practice update based on that rapid review online in Gastroenterology (2020. doi: 10.1053/j.gastro.2020.04.012).

Because of the widespread use of immunosuppressive or immune-modifying drugs, “It is understandable why patients with Crohn’s disease and ulcerative colitis have specific concerns and potential for increased risk of infection with SARS-CoV-2,” wrote David T. Rubin, MD, AGAF, of the University of Chicago and colleagues in the expert commentary.

They noted that, while association between GI symptoms and COVID-19 RNA in stool samples isn’t clear, given the reports of GI symptoms in COVID-19 patients – ranging from 10% (JAMA. 2020:323:1061-9) to half of patients (Am J Gastroenterol. 2020;115:766-73) – “the clinical implications of this are quite important.” In IBD patients, changes in digestive symptoms without accompanying fever or respiratory symptoms can be monitored for symptoms that could merit testing for the virus as well as “trigger additional treatment adjustments.”

In accordance with the IOIBD (International Organization for the Study of Inflammatory Bowel Disease) consensus, the update noted that IBD patients should continue going to infusion centers for therapies, provided that the centers use a COVID-19 screening protocol.

Patients with IBD who contract COVID-19 seem more likely to be hospitalized for one or the other disease, but that’s based on data from the international SECURE-IBD registry that had 164 patients as of the writing of the update. The update provides guidance for three scenarios for IBD patients during the pandemic:

• Patients not infected with SARS-CoV-2 should maintain their IBD therapies to sustain remission and avoid relapses. “Aside from the obvious negative consequences of a relapse, relapsing IBD will strain available medical resources, may require steroid therapy or necessitate hospitalization, outcomes that are all much worse than the known risks of existing IBD therapies,” Dr. Rubin and colleagues noted.
• Patients who are infected but have no symptoms of COVID-19 should have their dosing of prednisone adjusted to less than 20 mg/day or switched to budesonide; suspend thiopurines, methotrexate, and tofacitinib; and delay dosing of monoclonal antibodies (anti–tumor necrosis factor [anti-TNF] drugs, ustekinumab, or vedolizumab) for 2 weeks while their symptoms for COVID-19 are monitored. “Restarting therapy after 2 weeks if the patient has not developed manifestations of COVID-19 is reasonable,” wrote Dr. Rubin and colleagues. Emerging serial testing should indicate antibody status, but the effectiveness of stool testing for SARS-CoV-2 in these cases “remains to be seen.”
• In the patient with confirmed COVID-19, adjustment of IBD therapy “is appropriate, based on the understanding of the immune activity of the therapy and whether that therapy may worsen outcomes with COVID-19,” the update stated. Therapy adjustment should focus on reducing immune suppression during the active viral infection. Some studies are evaluating anticytokine-based therapies as COVID-19 treatments, so continued anti-TNF therapies might prevent acute respiratory distress syndrome and multiorgan failure, Dr. Rubin and colleagues wrote. “However, in the absence of those data, guidance is currently based on deciding whether to hold or to continue specific IBD therapies.”

The update considers most IBD therapies, specifically aminosalicylates, topical rectal therapy, dietary management, and antibiotics “safe and may be continued,” and oral budesonide can be continued if it’s needed for ongoing IBD control. However, corticosteroids “should be avoided and discontinued quickly.”

Likewise, during the acute stage of COVID-19, thiopurines, methotrexate, and tofacitinib should be discontinued, and anti-TNF drugs and ustekinumab should be stopped during viral illness. Holding vedolizumab during viral illness is also appropriate, according to the update, although the IOIBD group was uncertain if doing so was necessary.

If the IBD patient has digestive symptoms with COVID-19, ongoing supportive care of the COVID-19 is “reasonable,” but investigating the causes of the digestive symptoms “is critically important.” That should include ruling out enteric infections and confirming active inflammation with nonendoscopic testing. Endoscopy should be relegated to only urgent and emergent cases.

Management of IBD in COVID-19 patients also depends on disease severity. Safer therapies are indicated for mild disease, but withholding IBD therapy in moderate to severe cases may not be practical. “In this setting, the risks and benefits of escalating IBD therapy must be carefully weighed against the severity of the COVID-19,” Dr. Rubin and colleagues noted.

In hospitalized patients with severe COVID-19 and poor prognoses, “IBD therapy will likely take a back seat,” the update stated, although COVID-19 therapies should take the concomitant IBD into account. In patients with milder cases of COVID-19, IBD management should focus on acute manifestations, but intravenous steroid therapy shouldn’t exceed 3 days. The update urged providers to submit cases of IBD and confirmed COVID-19 to the SECURE-IBD registry at COVIDIBD.org.

Dr. Rubin disclosed financial relationships with AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene/Syneos, Gilead Sciences, Takeda, and many other pharmaceutical companies. Coauthors disclosed relationships with those companies and Medimmune, Novus Therapeutics, Osiris Therapeutics, RedHill Biopharma, Sanofi-Aventis, UCB Pharma, and multiple other pharmaceutical companies.

SOURCE: Rubin DT, et al. Gastroenterology. 2020:  doi: 10.1053/j.gastro.2020.04.012

Cancers of the gastrointestinal tract represented about one in four cancer cases in 2018 but more than one in three cancer-related deaths, underscoring the importance of preventive measures, according to an analysis of global cancer datasets that identified trends in five major GI cancer types – esophageal, stomach, colorectal, liver, and pancreatic – published in Gastroenterology.

“Although the incidence of some GI cancer types has decreased, this group of malignancies continues to pose major challenges to public health,” wrote Melina Arnold, PhD, of the International for Research on Cancer in Lyon, France, and colleagues. “Primary and secondary prevention measures are important for controlling these malignancies – most importantly, reducing consumption of tobacco and alcohol, obesity control, immunizing populations against hepatitis B virus infection, and screening for colorectal cancer.”

For example, the study found that the proportion of GI cancer deaths in Asia exceeds that of new cases, with the greatest disparity in China, while the opposite can be said of GI cancer trends in Europe and North America.

The study reported 4.8 million new cases of GI cancer and 3.4 million deaths worldwide in 2018. GI cancers accounted for 26% of the global cancer burden but 35% of cancer-related deaths. Incidence-to-death disparities were greatest for Africa, accounting for 4% of new cases and 5% of deaths; and Asia, with about 63% of new cases but 65% of deaths. The disparity was even wider in China, which accounted for 38% of worldwide cases but 41% of the deaths. Europe and North America, on the other hand, accounted for 26% of global cases but 23% of deaths. High death rates of these cancers are associated with late detection, Dr. Arnold and colleagues noted.

Regarding the five different types of GI cancer, the study reported the following:

• Esophageal cancer accounted for 572,000 new cases and 508,000 deaths in 2018, making it the sixth-most-deadly cancer worldwide. Rates in men are two to three times higher than in women. Eastern Asia has the highest rates, 12.2 per 100,000 person-years, followed by eastern Africa (8.3) and southern Africa (7.4). China alone accounts for 54% of the global burden. A large percentage of these cancers in developing countries are squamous cell carcinoma, the most common form of esophageal cancer globally, which has been linked to tobacco use, heavy alcohol consumption, opium intake, air pollution, and diet.
• Gastric cancer accounted for more than 1 million new cases and nearly 800,000 deaths in 2018. Again, the incidence is twice as high in men as in women, and eastern Asia has the highest rates of 22 per 100,000 vs. < 5 in Africa, North America, and northern Europe. Cardia gastric cancer (CGC), associated with obesity and gastroesophageal reflux disease, is more prevalent in Western countries, while noncardia gastric cancer (CG) is more prevalent in countries with higher rates of Helicobacter pylori infection. In the United States specifically, CGC is more common in non-Hispanic whites than other ethnic groups. Gastric cancer rates have been declining in recent years, although trends of CGC and cancer of the gastric corpus, which the study terms “a noncardia subsite,” among younger people “may lead to a deceleration or a reversal” of declining gastric cancer rates, stated Dr. Arnold and colleagues.
• Colorectal cancer remained the most commonly diagnosed GI cancer in 2018, accounting for 1.8 million cases and 881,000 deaths, which represents 1 in 10 cancer deaths. The highest incidence was found in Australia/New Zealand, the lowest in south and central Asia. Colorectal cancers are in “transition” from infection-related cancers to those related to “rapid societal and economic change.” Dr. Arnold and colleagues attributed these changes to higher dietary intake of fats, sugar, and animal-source foods and increases in sedentary behavior and obesity. Despite advances in cures for colorectal cancer, disparities continue, even in high-income countries, and screening programs have been limited, according to the study. Colorectal cancer will be “one of the main contributors” to the doubling of cancer rates in older adults by 2035.
• Liver cancer comprised 841,000 cases and 782,000 deaths in 2018, making it the sixth-most-diagnosed cancer but the fourth most deadly. “Transitioning countries” in eastern Asia, Micronesia, and northern Africa have the highest rates. In eastern Asia, hepatitis B infections and aflatoxins are the primary risk factors for hepatocellular carcinoma, while in Japan and Europe hepatitis C is the main cause for hepatocellular carcinoma. Decreases in both infections and aflatoxins may explain declines in liver cancer rates in those regions. Whereas in lower-risk areas, increasing liver cancer rates caused by more widespread obesity and diabetes may be offsetting declines in HBV and HCV rates.
• Pancreatic cancer was the 12th-most-common cancer but the seventh leading cause of cancer death, with 432,000 cases and 459,000 deaths in 2018. Wealthy countries have incidence and death rates three to four times higher than do less-developed countries, with rates highest in Europe, North America, and Australia/New Zealand. Because pancreatic cancer isn’t typically diagnosed until it is in the metastatic or locally advanced state, curative surgery isn’t feasible, Dr. Arnold and colleagues stated. Population aging and growth, along with advances in treating other types of cancers, mean that pancreatic cancer “has become or is set out to become one of the leading causes of cancer-related death in many countries,” Dr. Arnold and colleagues stated. They added that, in the European Union, pancreatic cancer is already the third-leading cause of cancer death after lung and colorectal cancer.

The findings, Dr. Arnold and colleagues wrote, underscore the shift of the cancer burden toward transitioning countries, “which are less equipped to manage this increasing burden.” In the United States, the rates of all five GI cancers in young adults (aged 25-49 years) have increased.

GI cancers, with the exception of colorectal cancers, also contribute disproportionately to cancer-related death rates, mostly because all but colorectal cancers are difficult to diagnose.

However, early detection and screening programs for gastric cancer in Japan and Korea, and esophageal cancer in China “have shown promising results,” Dr. Arnold and colleagues said. “Pancreatic cancer, on the other hand, is becoming a more important contributor to cancer-related mortality as a consequence of improved diagnosis and management of the historically most common forms of cancer death,” they wrote.

Prevention remains key, and lifestyle choices like smoking, alcohol intake, and physical activity are all drivers of GI cancer burden. “Primary and secondary prevention measures remain the most important tools to control this group of malignancies, particularly in light of their preventability and often dreadful prognosis,” Dr. Arnold and colleagues wrote.

Dr. Arnold and colleagues have no financial relationships to disclose.

SOURCE: Arnold M et al. Gastroenterology. 2020 Apr 2;S0016-5085(20)30452-2. doi: 10.1053/j.gastro.2020.02.068.

Cancers of the gastrointestinal tract represented about one in four cancer cases in 2018 but more than one in three cancer-related deaths, underscoring the importance of preventive measures, according to an analysis of global cancer datasets that identified trends in five major GI cancer types – esophageal, stomach, colorectal, liver, and pancreatic – published in Gastroenterology.

“Although the incidence of some GI cancer types has decreased, this group of malignancies continues to pose major challenges to public health,” wrote Melina Arnold, PhD, of the International for Research on Cancer in Lyon, France, and colleagues. “Primary and secondary prevention measures are important for controlling these malignancies – most importantly, reducing consumption of tobacco and alcohol, obesity control, immunizing populations against hepatitis B virus infection, and screening for colorectal cancer.”

For example, the study found that the proportion of GI cancer deaths in Asia exceeds that of new cases, with the greatest disparity in China, while the opposite can be said of GI cancer trends in Europe and North America.

The study reported 4.8 million new cases of GI cancer and 3.4 million deaths worldwide in 2018. GI cancers accounted for 26% of the global cancer burden but 35% of cancer-related deaths. Incidence-to-death disparities were greatest for Africa, accounting for 4% of new cases and 5% of deaths; and Asia, with about 63% of new cases but 65% of deaths. The disparity was even wider in China, which accounted for 38% of worldwide cases but 41% of the deaths. Europe and North America, on the other hand, accounted for 26% of global cases but 23% of deaths. High death rates of these cancers are associated with late detection, Dr. Arnold and colleagues noted.

Regarding the five different types of GI cancer, the study reported the following:

• Esophageal cancer accounted for 572,000 new cases and 508,000 deaths in 2018, making it the sixth-most-deadly cancer worldwide. Rates in men are two to three times higher than in women. Eastern Asia has the highest rates, 12.2 per 100,000 person-years, followed by eastern Africa (8.3) and southern Africa (7.4). China alone accounts for 54% of the global burden. A large percentage of these cancers in developing countries are squamous cell carcinoma, the most common form of esophageal cancer globally, which has been linked to tobacco use, heavy alcohol consumption, opium intake, air pollution, and diet.
• Gastric cancer accounted for more than 1 million new cases and nearly 800,000 deaths in 2018. Again, the incidence is twice as high in men as in women, and eastern Asia has the highest rates of 22 per 100,000 vs. < 5 in Africa, North America, and northern Europe. Cardia gastric cancer (CGC), associated with obesity and gastroesophageal reflux disease, is more prevalent in Western countries, while noncardia gastric cancer (CG) is more prevalent in countries with higher rates of Helicobacter pylori infection. In the United States specifically, CGC is more common in non-Hispanic whites than other ethnic groups. Gastric cancer rates have been declining in recent years, although trends of CGC and cancer of the gastric corpus, which the study terms “a noncardia subsite,” among younger people “may lead to a deceleration or a reversal” of declining gastric cancer rates, stated Dr. Arnold and colleagues.
• Colorectal cancer remained the most commonly diagnosed GI cancer in 2018, accounting for 1.8 million cases and 881,000 deaths, which represents 1 in 10 cancer deaths. The highest incidence was found in Australia/New Zealand, the lowest in south and central Asia. Colorectal cancers are in “transition” from infection-related cancers to those related to “rapid societal and economic change.” Dr. Arnold and colleagues attributed these changes to higher dietary intake of fats, sugar, and animal-source foods and increases in sedentary behavior and obesity. Despite advances in cures for colorectal cancer, disparities continue, even in high-income countries, and screening programs have been limited, according to the study. Colorectal cancer will be “one of the main contributors” to the doubling of cancer rates in older adults by 2035.
• Liver cancer comprised 841,000 cases and 782,000 deaths in 2018, making it the sixth-most-diagnosed cancer but the fourth most deadly. “Transitioning countries” in eastern Asia, Micronesia, and northern Africa have the highest rates. In eastern Asia, hepatitis B infections and aflatoxins are the primary risk factors for hepatocellular carcinoma, while in Japan and Europe hepatitis C is the main cause for hepatocellular carcinoma. Decreases in both infections and aflatoxins may explain declines in liver cancer rates in those regions. Whereas in lower-risk areas, increasing liver cancer rates caused by more widespread obesity and diabetes may be offsetting declines in HBV and HCV rates.
• Pancreatic cancer was the 12th-most-common cancer but the seventh leading cause of cancer death, with 432,000 cases and 459,000 deaths in 2018. Wealthy countries have incidence and death rates three to four times higher than do less-developed countries, with rates highest in Europe, North America, and Australia/New Zealand. Because pancreatic cancer isn’t typically diagnosed until it is in the metastatic or locally advanced state, curative surgery isn’t feasible, Dr. Arnold and colleagues stated. Population aging and growth, along with advances in treating other types of cancers, mean that pancreatic cancer “has become or is set out to become one of the leading causes of cancer-related death in many countries,” Dr. Arnold and colleagues stated. They added that, in the European Union, pancreatic cancer is already the third-leading cause of cancer death after lung and colorectal cancer.

The findings, Dr. Arnold and colleagues wrote, underscore the shift of the cancer burden toward transitioning countries, “which are less equipped to manage this increasing burden.” In the United States, the rates of all five GI cancers in young adults (aged 25-49 years) have increased.

GI cancers, with the exception of colorectal cancers, also contribute disproportionately to cancer-related death rates, mostly because all but colorectal cancers are difficult to diagnose.

However, early detection and screening programs for gastric cancer in Japan and Korea, and esophageal cancer in China “have shown promising results,” Dr. Arnold and colleagues said. “Pancreatic cancer, on the other hand, is becoming a more important contributor to cancer-related mortality as a consequence of improved diagnosis and management of the historically most common forms of cancer death,” they wrote.

Prevention remains key, and lifestyle choices like smoking, alcohol intake, and physical activity are all drivers of GI cancer burden. “Primary and secondary prevention measures remain the most important tools to control this group of malignancies, particularly in light of their preventability and often dreadful prognosis,” Dr. Arnold and colleagues wrote.

Dr. Arnold and colleagues have no financial relationships to disclose.

SOURCE: Arnold M et al. Gastroenterology. 2020 Apr 2;S0016-5085(20)30452-2. doi: 10.1053/j.gastro.2020.02.068.

Cancers of the gastrointestinal tract represented about one in four cancer cases in 2018 but more than one in three cancer-related deaths, underscoring the importance of preventive measures, according to an analysis of global cancer datasets that identified trends in five major GI cancer types – esophageal, stomach, colorectal, liver, and pancreatic – published in Gastroenterology.

“Although the incidence of some GI cancer types has decreased, this group of malignancies continues to pose major challenges to public health,” wrote Melina Arnold, PhD, of the International for Research on Cancer in Lyon, France, and colleagues. “Primary and secondary prevention measures are important for controlling these malignancies – most importantly, reducing consumption of tobacco and alcohol, obesity control, immunizing populations against hepatitis B virus infection, and screening for colorectal cancer.”

For example, the study found that the proportion of GI cancer deaths in Asia exceeds that of new cases, with the greatest disparity in China, while the opposite can be said of GI cancer trends in Europe and North America.

The study reported 4.8 million new cases of GI cancer and 3.4 million deaths worldwide in 2018. GI cancers accounted for 26% of the global cancer burden but 35% of cancer-related deaths. Incidence-to-death disparities were greatest for Africa, accounting for 4% of new cases and 5% of deaths; and Asia, with about 63% of new cases but 65% of deaths. The disparity was even wider in China, which accounted for 38% of worldwide cases but 41% of the deaths. Europe and North America, on the other hand, accounted for 26% of global cases but 23% of deaths. High death rates of these cancers are associated with late detection, Dr. Arnold and colleagues noted.

Regarding the five different types of GI cancer, the study reported the following:

• Esophageal cancer accounted for 572,000 new cases and 508,000 deaths in 2018, making it the sixth-most-deadly cancer worldwide. Rates in men are two to three times higher than in women. Eastern Asia has the highest rates, 12.2 per 100,000 person-years, followed by eastern Africa (8.3) and southern Africa (7.4). China alone accounts for 54% of the global burden. A large percentage of these cancers in developing countries are squamous cell carcinoma, the most common form of esophageal cancer globally, which has been linked to tobacco use, heavy alcohol consumption, opium intake, air pollution, and diet.
• Gastric cancer accounted for more than 1 million new cases and nearly 800,000 deaths in 2018. Again, the incidence is twice as high in men as in women, and eastern Asia has the highest rates of 22 per 100,000 vs. < 5 in Africa, North America, and northern Europe. Cardia gastric cancer (CGC), associated with obesity and gastroesophageal reflux disease, is more prevalent in Western countries, while noncardia gastric cancer (CG) is more prevalent in countries with higher rates of Helicobacter pylori infection. In the United States specifically, CGC is more common in non-Hispanic whites than other ethnic groups. Gastric cancer rates have been declining in recent years, although trends of CGC and cancer of the gastric corpus, which the study terms “a noncardia subsite,” among younger people “may lead to a deceleration or a reversal” of declining gastric cancer rates, stated Dr. Arnold and colleagues.
• Colorectal cancer remained the most commonly diagnosed GI cancer in 2018, accounting for 1.8 million cases and 881,000 deaths, which represents 1 in 10 cancer deaths. The highest incidence was found in Australia/New Zealand, the lowest in south and central Asia. Colorectal cancers are in “transition” from infection-related cancers to those related to “rapid societal and economic change.” Dr. Arnold and colleagues attributed these changes to higher dietary intake of fats, sugar, and animal-source foods and increases in sedentary behavior and obesity. Despite advances in cures for colorectal cancer, disparities continue, even in high-income countries, and screening programs have been limited, according to the study. Colorectal cancer will be “one of the main contributors” to the doubling of cancer rates in older adults by 2035.
• Liver cancer comprised 841,000 cases and 782,000 deaths in 2018, making it the sixth-most-diagnosed cancer but the fourth most deadly. “Transitioning countries” in eastern Asia, Micronesia, and northern Africa have the highest rates. In eastern Asia, hepatitis B infections and aflatoxins are the primary risk factors for hepatocellular carcinoma, while in Japan and Europe hepatitis C is the main cause for hepatocellular carcinoma. Decreases in both infections and aflatoxins may explain declines in liver cancer rates in those regions. Whereas in lower-risk areas, increasing liver cancer rates caused by more widespread obesity and diabetes may be offsetting declines in HBV and HCV rates.
• Pancreatic cancer was the 12th-most-common cancer but the seventh leading cause of cancer death, with 432,000 cases and 459,000 deaths in 2018. Wealthy countries have incidence and death rates three to four times higher than do less-developed countries, with rates highest in Europe, North America, and Australia/New Zealand. Because pancreatic cancer isn’t typically diagnosed until it is in the metastatic or locally advanced state, curative surgery isn’t feasible, Dr. Arnold and colleagues stated. Population aging and growth, along with advances in treating other types of cancers, mean that pancreatic cancer “has become or is set out to become one of the leading causes of cancer-related death in many countries,” Dr. Arnold and colleagues stated. They added that, in the European Union, pancreatic cancer is already the third-leading cause of cancer death after lung and colorectal cancer.

The findings, Dr. Arnold and colleagues wrote, underscore the shift of the cancer burden toward transitioning countries, “which are less equipped to manage this increasing burden.” In the United States, the rates of all five GI cancers in young adults (aged 25-49 years) have increased.

GI cancers, with the exception of colorectal cancers, also contribute disproportionately to cancer-related death rates, mostly because all but colorectal cancers are difficult to diagnose.

However, early detection and screening programs for gastric cancer in Japan and Korea, and esophageal cancer in China “have shown promising results,” Dr. Arnold and colleagues said. “Pancreatic cancer, on the other hand, is becoming a more important contributor to cancer-related mortality as a consequence of improved diagnosis and management of the historically most common forms of cancer death,” they wrote.

Prevention remains key, and lifestyle choices like smoking, alcohol intake, and physical activity are all drivers of GI cancer burden. “Primary and secondary prevention measures remain the most important tools to control this group of malignancies, particularly in light of their preventability and often dreadful prognosis,” Dr. Arnold and colleagues wrote.

Dr. Arnold and colleagues have no financial relationships to disclose.

SOURCE: Arnold M et al. Gastroenterology. 2020 Apr 2;S0016-5085(20)30452-2. doi: 10.1053/j.gastro.2020.02.068.