Federal Practitioner

The US Food and Drug Administration on Aug. 28 expanded its emergency use authorization (EUA) of remdesivir (Veklury) to include treatment of all adult and pediatric hospitalized COVID-19 patients, regardless of the severity of their disease.

An EUA of remdesivir issued in May allowed the drug to be used only for patients with severe COVID-19, specifically, COVID-19 patients with low blood oxygen levels or who need oxygen therapy or mechanical ventilation.

“Today, based on the Agency’s ongoing review of the EUA, including its review of the totality of scientific information now available, the FDA has determined that it is reasonable to believe Veklury may be effective for the treatment of suspected or laboratory-confirmed COVID-19 in all hospitalized adult and pediatric patients,” the FDA news release about the expanded EUA said. “The Agency’s review has also concluded that the known and potential benefits of Veklury outweigh the known and potential risks for these uses.”
 

‘Further evaluation’ needed

The EUA expansion is partially based on the results of a randomized, open-label trial that Gilead Sciences, remdesivir’s manufacturer, conducted at multiple sites.

The trial showed that a 5-day course of remdesivir was associated with statistically significant improvement among patients hospitalized with moderate COVID-19 in comparison with those receiving standard care. However, patients who were randomly assigned to a receive longer, 10-day remdesivir course had not improved significantly 11 days after treatment started, compared with those who received standard care.

Results with remdesivir in this trial and in two previously reported randomized trials varied, “raising the question of whether the discrepancies are artifacts of study design choices, including patient populations, or whether the drug is less efficacious than hoped,” wrote Erin K. McCreary, PharmD, and Derek C. Angus, MD, MPH, with the University of Pittsburgh School of Medicine, in an editorial that accompanied publication of the trials in JAMA.

Angus previously expressed concern that expanding remdesivir’s EUA could “interrupt or thwart efforts to execute the needed RCTs [randomized controlled trials].

“We think there really needs to be further evaluation of remdesivir in large-scale RCTs adequately powered to understand in which patients, at which dose, given at which point in the course of illness leads to what concrete and tangible improvement in clinical outcomes,” he told Medscape Medical News.

“At this point, remdesivir definitely holds promise, but given the cost to produce and distribute the drug, it seems crucial to know with more certainty how best to use it,” Angus said.

The EUA expansion is also partially based on results from a randomized, double-blind, placebo-controlled clinical trial that the National Institutes of Allergy and Infectious Diseases conducted. In that trial, there was a statistically significant reduction in median recovery time and higher odds of clinical improvement after 2 weeks for hospitalized patients who received remdesivir.

For hospitalized patients with mild to moderate disease, the results were consistent with the overall study results but were not statistically significant.
 

This article first appeared on Medscape.com.

The US Food and Drug Administration on Aug. 28 expanded its emergency use authorization (EUA) of remdesivir (Veklury) to include treatment of all adult and pediatric hospitalized COVID-19 patients, regardless of the severity of their disease.

An EUA of remdesivir issued in May allowed the drug to be used only for patients with severe COVID-19, specifically, COVID-19 patients with low blood oxygen levels or who need oxygen therapy or mechanical ventilation.

“Today, based on the Agency’s ongoing review of the EUA, including its review of the totality of scientific information now available, the FDA has determined that it is reasonable to believe Veklury may be effective for the treatment of suspected or laboratory-confirmed COVID-19 in all hospitalized adult and pediatric patients,” the FDA news release about the expanded EUA said. “The Agency’s review has also concluded that the known and potential benefits of Veklury outweigh the known and potential risks for these uses.”
 

‘Further evaluation’ needed

The EUA expansion is partially based on the results of a randomized, open-label trial that Gilead Sciences, remdesivir’s manufacturer, conducted at multiple sites.

The trial showed that a 5-day course of remdesivir was associated with statistically significant improvement among patients hospitalized with moderate COVID-19 in comparison with those receiving standard care. However, patients who were randomly assigned to a receive longer, 10-day remdesivir course had not improved significantly 11 days after treatment started, compared with those who received standard care.

Results with remdesivir in this trial and in two previously reported randomized trials varied, “raising the question of whether the discrepancies are artifacts of study design choices, including patient populations, or whether the drug is less efficacious than hoped,” wrote Erin K. McCreary, PharmD, and Derek C. Angus, MD, MPH, with the University of Pittsburgh School of Medicine, in an editorial that accompanied publication of the trials in JAMA.

Angus previously expressed concern that expanding remdesivir’s EUA could “interrupt or thwart efforts to execute the needed RCTs [randomized controlled trials].

“We think there really needs to be further evaluation of remdesivir in large-scale RCTs adequately powered to understand in which patients, at which dose, given at which point in the course of illness leads to what concrete and tangible improvement in clinical outcomes,” he told Medscape Medical News.

“At this point, remdesivir definitely holds promise, but given the cost to produce and distribute the drug, it seems crucial to know with more certainty how best to use it,” Angus said.

The EUA expansion is also partially based on results from a randomized, double-blind, placebo-controlled clinical trial that the National Institutes of Allergy and Infectious Diseases conducted. In that trial, there was a statistically significant reduction in median recovery time and higher odds of clinical improvement after 2 weeks for hospitalized patients who received remdesivir.

For hospitalized patients with mild to moderate disease, the results were consistent with the overall study results but were not statistically significant.
 

This article first appeared on Medscape.com.

The US Food and Drug Administration on Aug. 28 expanded its emergency use authorization (EUA) of remdesivir (Veklury) to include treatment of all adult and pediatric hospitalized COVID-19 patients, regardless of the severity of their disease.

An EUA of remdesivir issued in May allowed the drug to be used only for patients with severe COVID-19, specifically, COVID-19 patients with low blood oxygen levels or who need oxygen therapy or mechanical ventilation.

“Today, based on the Agency’s ongoing review of the EUA, including its review of the totality of scientific information now available, the FDA has determined that it is reasonable to believe Veklury may be effective for the treatment of suspected or laboratory-confirmed COVID-19 in all hospitalized adult and pediatric patients,” the FDA news release about the expanded EUA said. “The Agency’s review has also concluded that the known and potential benefits of Veklury outweigh the known and potential risks for these uses.”
 

‘Further evaluation’ needed

The EUA expansion is partially based on the results of a randomized, open-label trial that Gilead Sciences, remdesivir’s manufacturer, conducted at multiple sites.

The trial showed that a 5-day course of remdesivir was associated with statistically significant improvement among patients hospitalized with moderate COVID-19 in comparison with those receiving standard care. However, patients who were randomly assigned to a receive longer, 10-day remdesivir course had not improved significantly 11 days after treatment started, compared with those who received standard care.

Results with remdesivir in this trial and in two previously reported randomized trials varied, “raising the question of whether the discrepancies are artifacts of study design choices, including patient populations, or whether the drug is less efficacious than hoped,” wrote Erin K. McCreary, PharmD, and Derek C. Angus, MD, MPH, with the University of Pittsburgh School of Medicine, in an editorial that accompanied publication of the trials in JAMA.

Angus previously expressed concern that expanding remdesivir’s EUA could “interrupt or thwart efforts to execute the needed RCTs [randomized controlled trials].

“We think there really needs to be further evaluation of remdesivir in large-scale RCTs adequately powered to understand in which patients, at which dose, given at which point in the course of illness leads to what concrete and tangible improvement in clinical outcomes,” he told Medscape Medical News.

“At this point, remdesivir definitely holds promise, but given the cost to produce and distribute the drug, it seems crucial to know with more certainty how best to use it,” Angus said.

The EUA expansion is also partially based on results from a randomized, double-blind, placebo-controlled clinical trial that the National Institutes of Allergy and Infectious Diseases conducted. In that trial, there was a statistically significant reduction in median recovery time and higher odds of clinical improvement after 2 weeks for hospitalized patients who received remdesivir.

For hospitalized patients with mild to moderate disease, the results were consistent with the overall study results but were not statistically significant.
 

This article first appeared on Medscape.com.

Microorganisms in the human digestive tract are linked to 29 specific health conditions, including chronic obstructive pulmonary disease, high blood pressure, and type 2 diabetes, according to a genome analysis in more than 400,000 individuals.

European Society of Cardiology

Although previous studies have suggested a link between gut microbiota and diseases in humans, “the extent to which the human gut microbiome can be considered a determinant of disease and healthy aging remains unknown,” Hilde E. Groot, MD, of the University of Groningen (The Netherlands), said in a presentation at the virtual annual congress of the European Society of Cardiology.

To identify the spectrum of diseases linked to the gut microbiome, the researchers identified 422,417 unrelated adults of White British ancestry with genotype and matching genetic data. The average age of the participants was 57 years and 46% were male.

The researchers conducted a phenomewide association study including 35 distinct single-nucleotide polymorphisms (SNPs) that are known to influence the microbiome of the human gut.

Overall, seven SNPs were significantly associated with 29 disease outcomes including hypertension, type 2 diabetes, hypercholesterolemia, heart failure, renal failure, and osteoarthritis.

In addition, after a further sensitivity analysis using a Mendelian randomization (MR) approach, associations between Ruminococcus flavefaciens and hypertension and between Clostridium and platelet count might point to a causal link, the researchers said.

“Over the past few years, the amount of research concerning the human gut microbiome and the associations with health and disease has tremendously increased. However, most studies investigated one or a few traits. The strength of our study is the possibility to cover a wide range of traits simultaneously within one population,” Dr. Groot said in an interview.

“Our data support the hypothesis that the human gut microbiome is a complex system, involved in many pathophysiological mechanisms in the human body. So, our results are additional to earlier research and strengthen this hypothesis,” Dr. Groot added.

“Microbiota and their metabolites might be of importance in the interplay between overlapping pathophysiological processes, and could serve as potential therapeutic targets for the maintenance of health and prevention and treatment of cardiovascular diseases. However, before it is possible to give advice for the public and medical practice, further research is needed to study causality,” she emphasized.

“Currently, it is too soon to advise patients concerning their microbiome,” Dr. Groot noted. “However, genetic studies like ours might help other researchers to study causality between the gut microbiome and particular traits, which might potentially lead to new therapeutic targets. Next to genetic variants as a proxy, we’re currently studying the gut microbiome composition in myocardial infarction patients and healthy controls in a longitudinal setting.”

“Previous studies have suggested a potential link between the gut microbiome and the development of cardiovascular disease, type 2 diabetes mellitus, and other chronic disorders,” Carol Ann Remme, MD, of the Amsterdam University Medical Center, said in an interview. “However, it is challenging to study the effect of gut microbiome composition in large patient cohorts. As an alternative approach, the study authors showed in a very large population that genetic variants previously shown to influence gut microbiome composition were significantly associated with conditions such as hypertension, type 2 diabetes, hypercholesterolemia, and heart failure.”

The study is unique in that it employed a very large cohort of more than 400,000 individuals, which is typically required to be able to draw clear conclusions, Dr. Remme continued. “The authors were able to further refine their findings by linking genetic variants known to influence specific gut bacteria to some particular disorders,” she noted.

“It is becoming increasingly clear that an individual’s gut microbiome composition, which is defined by both genetic and environmental factors such as diet, may affect his/her susceptibility to certain diseases – including cardiovascular – in addition to disease progression and outcome,” said Dr. Remme. “This may ultimately lead to development of novel, personalized strategies for risk stratification in addition to potential preventive measures targeting the gut microbiome. I expect this area of research will become increasingly important in the coming years.”

The study received no outside funding. Dr. Groot and colleagues had no financial conflicts to disclose. Dr. Remme had no financial conflicts to disclose.

Microorganisms in the human digestive tract are linked to 29 specific health conditions, including chronic obstructive pulmonary disease, high blood pressure, and type 2 diabetes, according to a genome analysis in more than 400,000 individuals.

European Society of Cardiology

Although previous studies have suggested a link between gut microbiota and diseases in humans, “the extent to which the human gut microbiome can be considered a determinant of disease and healthy aging remains unknown,” Hilde E. Groot, MD, of the University of Groningen (The Netherlands), said in a presentation at the virtual annual congress of the European Society of Cardiology.

To identify the spectrum of diseases linked to the gut microbiome, the researchers identified 422,417 unrelated adults of White British ancestry with genotype and matching genetic data. The average age of the participants was 57 years and 46% were male.

The researchers conducted a phenomewide association study including 35 distinct single-nucleotide polymorphisms (SNPs) that are known to influence the microbiome of the human gut.

Overall, seven SNPs were significantly associated with 29 disease outcomes including hypertension, type 2 diabetes, hypercholesterolemia, heart failure, renal failure, and osteoarthritis.

In addition, after a further sensitivity analysis using a Mendelian randomization (MR) approach, associations between Ruminococcus flavefaciens and hypertension and between Clostridium and platelet count might point to a causal link, the researchers said.

“Over the past few years, the amount of research concerning the human gut microbiome and the associations with health and disease has tremendously increased. However, most studies investigated one or a few traits. The strength of our study is the possibility to cover a wide range of traits simultaneously within one population,” Dr. Groot said in an interview.

“Our data support the hypothesis that the human gut microbiome is a complex system, involved in many pathophysiological mechanisms in the human body. So, our results are additional to earlier research and strengthen this hypothesis,” Dr. Groot added.

“Microbiota and their metabolites might be of importance in the interplay between overlapping pathophysiological processes, and could serve as potential therapeutic targets for the maintenance of health and prevention and treatment of cardiovascular diseases. However, before it is possible to give advice for the public and medical practice, further research is needed to study causality,” she emphasized.

“Currently, it is too soon to advise patients concerning their microbiome,” Dr. Groot noted. “However, genetic studies like ours might help other researchers to study causality between the gut microbiome and particular traits, which might potentially lead to new therapeutic targets. Next to genetic variants as a proxy, we’re currently studying the gut microbiome composition in myocardial infarction patients and healthy controls in a longitudinal setting.”

“Previous studies have suggested a potential link between the gut microbiome and the development of cardiovascular disease, type 2 diabetes mellitus, and other chronic disorders,” Carol Ann Remme, MD, of the Amsterdam University Medical Center, said in an interview. “However, it is challenging to study the effect of gut microbiome composition in large patient cohorts. As an alternative approach, the study authors showed in a very large population that genetic variants previously shown to influence gut microbiome composition were significantly associated with conditions such as hypertension, type 2 diabetes, hypercholesterolemia, and heart failure.”

The study is unique in that it employed a very large cohort of more than 400,000 individuals, which is typically required to be able to draw clear conclusions, Dr. Remme continued. “The authors were able to further refine their findings by linking genetic variants known to influence specific gut bacteria to some particular disorders,” she noted.

“It is becoming increasingly clear that an individual’s gut microbiome composition, which is defined by both genetic and environmental factors such as diet, may affect his/her susceptibility to certain diseases – including cardiovascular – in addition to disease progression and outcome,” said Dr. Remme. “This may ultimately lead to development of novel, personalized strategies for risk stratification in addition to potential preventive measures targeting the gut microbiome. I expect this area of research will become increasingly important in the coming years.”

The study received no outside funding. Dr. Groot and colleagues had no financial conflicts to disclose. Dr. Remme had no financial conflicts to disclose.

Microorganisms in the human digestive tract are linked to 29 specific health conditions, including chronic obstructive pulmonary disease, high blood pressure, and type 2 diabetes, according to a genome analysis in more than 400,000 individuals.

European Society of Cardiology

Although previous studies have suggested a link between gut microbiota and diseases in humans, “the extent to which the human gut microbiome can be considered a determinant of disease and healthy aging remains unknown,” Hilde E. Groot, MD, of the University of Groningen (The Netherlands), said in a presentation at the virtual annual congress of the European Society of Cardiology.

To identify the spectrum of diseases linked to the gut microbiome, the researchers identified 422,417 unrelated adults of White British ancestry with genotype and matching genetic data. The average age of the participants was 57 years and 46% were male.

The researchers conducted a phenomewide association study including 35 distinct single-nucleotide polymorphisms (SNPs) that are known to influence the microbiome of the human gut.

Overall, seven SNPs were significantly associated with 29 disease outcomes including hypertension, type 2 diabetes, hypercholesterolemia, heart failure, renal failure, and osteoarthritis.

In addition, after a further sensitivity analysis using a Mendelian randomization (MR) approach, associations between Ruminococcus flavefaciens and hypertension and between Clostridium and platelet count might point to a causal link, the researchers said.

“Over the past few years, the amount of research concerning the human gut microbiome and the associations with health and disease has tremendously increased. However, most studies investigated one or a few traits. The strength of our study is the possibility to cover a wide range of traits simultaneously within one population,” Dr. Groot said in an interview.

“Our data support the hypothesis that the human gut microbiome is a complex system, involved in many pathophysiological mechanisms in the human body. So, our results are additional to earlier research and strengthen this hypothesis,” Dr. Groot added.

“Microbiota and their metabolites might be of importance in the interplay between overlapping pathophysiological processes, and could serve as potential therapeutic targets for the maintenance of health and prevention and treatment of cardiovascular diseases. However, before it is possible to give advice for the public and medical practice, further research is needed to study causality,” she emphasized.

“Currently, it is too soon to advise patients concerning their microbiome,” Dr. Groot noted. “However, genetic studies like ours might help other researchers to study causality between the gut microbiome and particular traits, which might potentially lead to new therapeutic targets. Next to genetic variants as a proxy, we’re currently studying the gut microbiome composition in myocardial infarction patients and healthy controls in a longitudinal setting.”

“Previous studies have suggested a potential link between the gut microbiome and the development of cardiovascular disease, type 2 diabetes mellitus, and other chronic disorders,” Carol Ann Remme, MD, of the Amsterdam University Medical Center, said in an interview. “However, it is challenging to study the effect of gut microbiome composition in large patient cohorts. As an alternative approach, the study authors showed in a very large population that genetic variants previously shown to influence gut microbiome composition were significantly associated with conditions such as hypertension, type 2 diabetes, hypercholesterolemia, and heart failure.”

The study is unique in that it employed a very large cohort of more than 400,000 individuals, which is typically required to be able to draw clear conclusions, Dr. Remme continued. “The authors were able to further refine their findings by linking genetic variants known to influence specific gut bacteria to some particular disorders,” she noted.

“It is becoming increasingly clear that an individual’s gut microbiome composition, which is defined by both genetic and environmental factors such as diet, may affect his/her susceptibility to certain diseases – including cardiovascular – in addition to disease progression and outcome,” said Dr. Remme. “This may ultimately lead to development of novel, personalized strategies for risk stratification in addition to potential preventive measures targeting the gut microbiome. I expect this area of research will become increasingly important in the coming years.”

The study received no outside funding. Dr. Groot and colleagues had no financial conflicts to disclose. Dr. Remme had no financial conflicts to disclose.

The US Food and Drug Administration has removed two senior public relations employees, one of whom advised the agency against unbridled promotion of convalescent blood plasma as a treatment for people with COVID-19, multiple media outlets reported Aug. 28.

Officials claim the dismissals are coincidental and are not related to a controversy about whether claims regarding convalescent plasma therapy that were put forth by President Donald Trump and FDA Commissioner Stephen M. Hahn, MD, were exaggerated, according to reports from The New York Times , CNN, and elsewhere.

One of the PR employees, Emily Miller, was on the job less than 2 weeks. The White House named her FDA chief spokeswoman 11 days ago, but Hahn removed her from that post Aug. 28.

On Aug. 27, the US Department of Health and Human Services terminated the contract for Wayne L. Pines, a PR consultant to the FDA. Pines reportedly advised Hahn to apologize for making misleading claims about the therapeutic benefits of convalescent plasma therapy for COVID-19.

The FDA did not respond to multiple requests for comment.

The controversy stems from comments Hahn made about the announcement of the emergency use authorization for convalescent plasma for patients with COVID-19. He said that plasma had been found to save the lives of 35 out of every 100 people who were treated. That statement was later found to be erroneous because he presented a relative risk reduction as an absolute decrease in risk. He later apologized via Twitter.

Researchers running clinical trials to evaluate the efficacy of convalescent plasma for COVID-19 are concerned that the emergency use authorization could thwart efforts to recruit participants for their studies.

This article first appeared on Medscape.com.

The US Food and Drug Administration has removed two senior public relations employees, one of whom advised the agency against unbridled promotion of convalescent blood plasma as a treatment for people with COVID-19, multiple media outlets reported Aug. 28.

Officials claim the dismissals are coincidental and are not related to a controversy about whether claims regarding convalescent plasma therapy that were put forth by President Donald Trump and FDA Commissioner Stephen M. Hahn, MD, were exaggerated, according to reports from The New York Times , CNN, and elsewhere.

One of the PR employees, Emily Miller, was on the job less than 2 weeks. The White House named her FDA chief spokeswoman 11 days ago, but Hahn removed her from that post Aug. 28.

On Aug. 27, the US Department of Health and Human Services terminated the contract for Wayne L. Pines, a PR consultant to the FDA. Pines reportedly advised Hahn to apologize for making misleading claims about the therapeutic benefits of convalescent plasma therapy for COVID-19.

The FDA did not respond to multiple requests for comment.

The controversy stems from comments Hahn made about the announcement of the emergency use authorization for convalescent plasma for patients with COVID-19. He said that plasma had been found to save the lives of 35 out of every 100 people who were treated. That statement was later found to be erroneous because he presented a relative risk reduction as an absolute decrease in risk. He later apologized via Twitter.

Researchers running clinical trials to evaluate the efficacy of convalescent plasma for COVID-19 are concerned that the emergency use authorization could thwart efforts to recruit participants for their studies.

This article first appeared on Medscape.com.

The US Food and Drug Administration has removed two senior public relations employees, one of whom advised the agency against unbridled promotion of convalescent blood plasma as a treatment for people with COVID-19, multiple media outlets reported Aug. 28.

Officials claim the dismissals are coincidental and are not related to a controversy about whether claims regarding convalescent plasma therapy that were put forth by President Donald Trump and FDA Commissioner Stephen M. Hahn, MD, were exaggerated, according to reports from The New York Times , CNN, and elsewhere.

One of the PR employees, Emily Miller, was on the job less than 2 weeks. The White House named her FDA chief spokeswoman 11 days ago, but Hahn removed her from that post Aug. 28.

On Aug. 27, the US Department of Health and Human Services terminated the contract for Wayne L. Pines, a PR consultant to the FDA. Pines reportedly advised Hahn to apologize for making misleading claims about the therapeutic benefits of convalescent plasma therapy for COVID-19.

The FDA did not respond to multiple requests for comment.

The controversy stems from comments Hahn made about the announcement of the emergency use authorization for convalescent plasma for patients with COVID-19. He said that plasma had been found to save the lives of 35 out of every 100 people who were treated. That statement was later found to be erroneous because he presented a relative risk reduction as an absolute decrease in risk. He later apologized via Twitter.

Researchers running clinical trials to evaluate the efficacy of convalescent plasma for COVID-19 are concerned that the emergency use authorization could thwart efforts to recruit participants for their studies.

This article first appeared on Medscape.com.

The SGLT2 inhibitor drug class solidified its role as a major, new treatment for patients with heart failure with reduced ejection fraction and no diabetes, with results from a second large, controlled trial showing clear efficacy and safety in this population.

Patients with heart failure with reduced ejection fraction (HFrEF) treated with the sodium glucose cotransporter 2 (SGLT2) inhibitor empagliflozin (Jardiance) had a statistically significant 25% relative cut in their incidence of cardiovascular death or first heart failure hospitalization, compared with placebo-treated controls when added on top of standard HFrEF treatment, and this benefit was consistent regardless of whether the treated patients also had type 2 diabetes, Milton Packer, MD, reported at the virtual annual congress of the European Society of Cardiology.

This 25% drop in the primary endpoint with empagliflozin treatment in the EMPEROR-Reduced trial exactly matched the cut in incidence of cardiovascular death or heart failure hospitalization produced by treatment with a another SGLT2 inhibitor, dapagliflozin (Farxiga), in the DAPA-HF trial (N Engl J Med. 2019 Nov 21;381[21]:1995-2008).

The performance of these two SGLT2 inhibitors was “incredibly consistent” across the their respective trials run in HFrEF patients with and without type 2 diabetes, and the combined evidence base of the two trials makes for “really compelling evidence” of both safety and efficacy that should prompt a change to U.S. practice, with both of these drugs forming a new cornerstone of HFrEF treatment, Dr. Packer said.
 

Results plant drug class firmly as HFrEF treatment

Dr. Packer stressed in his presentation that optimal treatment of patients with HFrEF now demands use of one of these two SGLT2 inhibitors, as well as sacubitril plus valsartan (Entresto), a beta-blocker, and a mineralocorticoid receptor antagonist, plus a diuretic as a fifth drug class for the many HFrEF patients who also need treatment for fluid overload. He further advocated for rapid introduction of these four cornerstone agents with proven survival benefits once a patient receives a HFrEF diagnosis, suggesting that sacubitril plus valsartan, an SGLT2 inhibitor, a beta-blocker, and a mineralocorticoid receptor antagonist could all be initiated within 6 weeks or less while acknowledging that optimal up-titration of the beta-blocker would likely take longer.

The order in which a patient starts these drugs shouldn’t matter, and there currently seems to be no evidence that clearly points toward using either dapagliflozin or empagliflozin over the other, Dr. Packer added.

In recognition of the importance of sending a message to heart failure clinicians about the newly proven efficacy of SGLT2 inhibitors in HFrEF patients, the American College of Cardiology and American Heart Association are now drafting an “expert decision pathway” to help clinicians as they enter this new prescribing space. This interim guidance should come out before the end of 2020, prior to release of fully revised HFrEF management guidelines in 2021, said Athena Poppas, MD, president of the ACC, in an interview.

“There is clearly need for education” that can help guide physicians who care for HFrEF patients on how to introduce an SGLT2 inhibitor along with the additional, lengthy list of drug classes proven to benefit these patients, noted Dr. Poppas, who is also a professor and chief of cardiology at the Brown University in Providence, R.I. Physicians may find that they need extra backup for successfully starting both sacubitril plus valsartan and an SGLT2 inhibitor in HFrEF patients because recent history has shown substantial pushback from third-party payers in reimbursing for these relatively expensive drugs, Dr. Poppas noted. She added that this is a problem that may be compounded when patients should ideally get both drug classes.

Physicians who care for heart failure patients have their own history of dragging their feet when adding new drugs to the regimens HFrEF patients receive. The angiotensin converting enzyme inhibitors and beta-blockers took about 17 years each to start reaching a majority of U.S. HFrEF patients, and sacubitril plus valsartan is now used on perhaps a quarter to a third of HFrEF patients despite receiving Food and Drug Administration approval for these patients in mid 2015, noted Christopher M. O’Connor, MD, a heart failure specialist and president of the Inova Heart and Vascular Institute in Fairfax, Va.

Despite dapagliflozin receiving FDA approval in May 2020 for treating HFrEF in patients without diabetes, early uptake in U.S. practice has been very slow, with findings from large U.S. patient registries suggesting that perhaps 1% of suitable HFrEF patients currently get the drug, estimated Dr. O’Connor in an interview.

Given how strong the evidence now is for benefit and safety from dapagliflozin and empagliflozin, it may take as little as 5 years to reach greater than 50% penetration of one of these drugs into U.S. HFrEF patient populations, suggested Dr. Packer, a distinguished scholar in cardiovascular science at Baylor University Medical Center in Dallas.
 

EMPEROR-Reduced outcomes

The road to routine use of these SGLT2 inhibitor drugs should be hastened by empagliflozin’s impressive performance in EMPEROR-Reduced, in which the drug scored highly significant benefits over placebo for the prespecified primary and two major secondary endpoints, one of which was a measure of preserved renal function.

The trial randomized 3,730 patients at 520 sites in 20 countries during 2017-2019 and followed them on treatment for a median of 16 months. All patients had a left ventricular ejection fraction of 40% or less, and roughly three-quarters had New York Heart Association (NYHA) class II function, nearly one-quarter had class III function, and fewer than 1% of patients fell into the class IV category.

The primary endpoint occurred in 19% of the empagliflozin-treated patients and in 25% of those who received placebo. Among the half of patients with diabetes in the trial, the relative risk reduction by empagliflozin compared with placebo was a statistically significant 28%; among those without diabetes, it was a statistically significant 22%. Concurrently with Dr. Packer’s report, the results appeared in an article posted online (N Engl J Med. 2020 Aug 29. doi: 10.1056/NEJMoa2022190).

The study also had two main prespecified secondary endpoints: the incidence of total hospitalizations for heart failure, both first and recurrent, which fell by 30% in the empagliflozin-treated patients, compared with placebo, and the rate of declining renal function during the 16 months of the study as measured by estimated glomerular filtration rate, which dropped by roughly 1 mL/min per 1.73 m² among the empagliflozin recipients and by about 4 mL/min/ per 1.73 m² in the placebo patients.

Treatment with empagliflozin also achieved a notable, statistically significant 50% drop in major adverse renal events, consistent with the performance of other drugs in the class.

“Renal protection is a big plus” of empagliflozin in this trial and from the other SGLT2 inhibitors in prior studies, noted Dr. O’Connor.

The EMPEROR-Reduced results also showed an important benefit for HFrEF patients from empagliflozin not previously seen as quickly with any other drug class, noted Dr. Packer. The SGLT2 inhibitor led to statistically a significant slowing in the progression of patients from NYHA class II function to class III, compared with placebo, and it also significantly promoted the recovery of patients from NYHA class III to class II, an effect that became apparent within the first month on treatment and a benefit that is a “big deal” for patients because it represents a “significant change in functional capacity.” This additional dimension of empagliflozin’s benefit “really impressed me,” Dr. Packer said.

EMPEROR-Reduced was funded by Boehringer Ingelheim and Eli Lilly, the companies that market empagliflozin. Dr. Packer has received personal fees from Boehringer Ingelheim and Eli Lilly and from several other companies. Dr. Poppas and Dr. O’Connor had no relevant disclosures.
 

[email protected]

SOURCE: Packer M. ESC 2020. N Engl J Med. 2020 Aug 29. doi: 10.1056/NEJMoa2022190.

The SGLT2 inhibitor drug class solidified its role as a major, new treatment for patients with heart failure with reduced ejection fraction and no diabetes, with results from a second large, controlled trial showing clear efficacy and safety in this population.

Patients with heart failure with reduced ejection fraction (HFrEF) treated with the sodium glucose cotransporter 2 (SGLT2) inhibitor empagliflozin (Jardiance) had a statistically significant 25% relative cut in their incidence of cardiovascular death or first heart failure hospitalization, compared with placebo-treated controls when added on top of standard HFrEF treatment, and this benefit was consistent regardless of whether the treated patients also had type 2 diabetes, Milton Packer, MD, reported at the virtual annual congress of the European Society of Cardiology.

This 25% drop in the primary endpoint with empagliflozin treatment in the EMPEROR-Reduced trial exactly matched the cut in incidence of cardiovascular death or heart failure hospitalization produced by treatment with a another SGLT2 inhibitor, dapagliflozin (Farxiga), in the DAPA-HF trial (N Engl J Med. 2019 Nov 21;381[21]:1995-2008).

The performance of these two SGLT2 inhibitors was “incredibly consistent” across the their respective trials run in HFrEF patients with and without type 2 diabetes, and the combined evidence base of the two trials makes for “really compelling evidence” of both safety and efficacy that should prompt a change to U.S. practice, with both of these drugs forming a new cornerstone of HFrEF treatment, Dr. Packer said.
 

Results plant drug class firmly as HFrEF treatment

Dr. Packer stressed in his presentation that optimal treatment of patients with HFrEF now demands use of one of these two SGLT2 inhibitors, as well as sacubitril plus valsartan (Entresto), a beta-blocker, and a mineralocorticoid receptor antagonist, plus a diuretic as a fifth drug class for the many HFrEF patients who also need treatment for fluid overload. He further advocated for rapid introduction of these four cornerstone agents with proven survival benefits once a patient receives a HFrEF diagnosis, suggesting that sacubitril plus valsartan, an SGLT2 inhibitor, a beta-blocker, and a mineralocorticoid receptor antagonist could all be initiated within 6 weeks or less while acknowledging that optimal up-titration of the beta-blocker would likely take longer.

The order in which a patient starts these drugs shouldn’t matter, and there currently seems to be no evidence that clearly points toward using either dapagliflozin or empagliflozin over the other, Dr. Packer added.

In recognition of the importance of sending a message to heart failure clinicians about the newly proven efficacy of SGLT2 inhibitors in HFrEF patients, the American College of Cardiology and American Heart Association are now drafting an “expert decision pathway” to help clinicians as they enter this new prescribing space. This interim guidance should come out before the end of 2020, prior to release of fully revised HFrEF management guidelines in 2021, said Athena Poppas, MD, president of the ACC, in an interview.

“There is clearly need for education” that can help guide physicians who care for HFrEF patients on how to introduce an SGLT2 inhibitor along with the additional, lengthy list of drug classes proven to benefit these patients, noted Dr. Poppas, who is also a professor and chief of cardiology at the Brown University in Providence, R.I. Physicians may find that they need extra backup for successfully starting both sacubitril plus valsartan and an SGLT2 inhibitor in HFrEF patients because recent history has shown substantial pushback from third-party payers in reimbursing for these relatively expensive drugs, Dr. Poppas noted. She added that this is a problem that may be compounded when patients should ideally get both drug classes.

Physicians who care for heart failure patients have their own history of dragging their feet when adding new drugs to the regimens HFrEF patients receive. The angiotensin converting enzyme inhibitors and beta-blockers took about 17 years each to start reaching a majority of U.S. HFrEF patients, and sacubitril plus valsartan is now used on perhaps a quarter to a third of HFrEF patients despite receiving Food and Drug Administration approval for these patients in mid 2015, noted Christopher M. O’Connor, MD, a heart failure specialist and president of the Inova Heart and Vascular Institute in Fairfax, Va.

Despite dapagliflozin receiving FDA approval in May 2020 for treating HFrEF in patients without diabetes, early uptake in U.S. practice has been very slow, with findings from large U.S. patient registries suggesting that perhaps 1% of suitable HFrEF patients currently get the drug, estimated Dr. O’Connor in an interview.

Given how strong the evidence now is for benefit and safety from dapagliflozin and empagliflozin, it may take as little as 5 years to reach greater than 50% penetration of one of these drugs into U.S. HFrEF patient populations, suggested Dr. Packer, a distinguished scholar in cardiovascular science at Baylor University Medical Center in Dallas.
 

EMPEROR-Reduced outcomes

The road to routine use of these SGLT2 inhibitor drugs should be hastened by empagliflozin’s impressive performance in EMPEROR-Reduced, in which the drug scored highly significant benefits over placebo for the prespecified primary and two major secondary endpoints, one of which was a measure of preserved renal function.

The trial randomized 3,730 patients at 520 sites in 20 countries during 2017-2019 and followed them on treatment for a median of 16 months. All patients had a left ventricular ejection fraction of 40% or less, and roughly three-quarters had New York Heart Association (NYHA) class II function, nearly one-quarter had class III function, and fewer than 1% of patients fell into the class IV category.

The primary endpoint occurred in 19% of the empagliflozin-treated patients and in 25% of those who received placebo. Among the half of patients with diabetes in the trial, the relative risk reduction by empagliflozin compared with placebo was a statistically significant 28%; among those without diabetes, it was a statistically significant 22%. Concurrently with Dr. Packer’s report, the results appeared in an article posted online (N Engl J Med. 2020 Aug 29. doi: 10.1056/NEJMoa2022190).

The study also had two main prespecified secondary endpoints: the incidence of total hospitalizations for heart failure, both first and recurrent, which fell by 30% in the empagliflozin-treated patients, compared with placebo, and the rate of declining renal function during the 16 months of the study as measured by estimated glomerular filtration rate, which dropped by roughly 1 mL/min per 1.73 m² among the empagliflozin recipients and by about 4 mL/min/ per 1.73 m² in the placebo patients.

Treatment with empagliflozin also achieved a notable, statistically significant 50% drop in major adverse renal events, consistent with the performance of other drugs in the class.

“Renal protection is a big plus” of empagliflozin in this trial and from the other SGLT2 inhibitors in prior studies, noted Dr. O’Connor.

The EMPEROR-Reduced results also showed an important benefit for HFrEF patients from empagliflozin not previously seen as quickly with any other drug class, noted Dr. Packer. The SGLT2 inhibitor led to statistically a significant slowing in the progression of patients from NYHA class II function to class III, compared with placebo, and it also significantly promoted the recovery of patients from NYHA class III to class II, an effect that became apparent within the first month on treatment and a benefit that is a “big deal” for patients because it represents a “significant change in functional capacity.” This additional dimension of empagliflozin’s benefit “really impressed me,” Dr. Packer said.

EMPEROR-Reduced was funded by Boehringer Ingelheim and Eli Lilly, the companies that market empagliflozin. Dr. Packer has received personal fees from Boehringer Ingelheim and Eli Lilly and from several other companies. Dr. Poppas and Dr. O’Connor had no relevant disclosures.
 

[email protected]

SOURCE: Packer M. ESC 2020. N Engl J Med. 2020 Aug 29. doi: 10.1056/NEJMoa2022190.

The SGLT2 inhibitor drug class solidified its role as a major, new treatment for patients with heart failure with reduced ejection fraction and no diabetes, with results from a second large, controlled trial showing clear efficacy and safety in this population.

Patients with heart failure with reduced ejection fraction (HFrEF) treated with the sodium glucose cotransporter 2 (SGLT2) inhibitor empagliflozin (Jardiance) had a statistically significant 25% relative cut in their incidence of cardiovascular death or first heart failure hospitalization, compared with placebo-treated controls when added on top of standard HFrEF treatment, and this benefit was consistent regardless of whether the treated patients also had type 2 diabetes, Milton Packer, MD, reported at the virtual annual congress of the European Society of Cardiology.

This 25% drop in the primary endpoint with empagliflozin treatment in the EMPEROR-Reduced trial exactly matched the cut in incidence of cardiovascular death or heart failure hospitalization produced by treatment with a another SGLT2 inhibitor, dapagliflozin (Farxiga), in the DAPA-HF trial (N Engl J Med. 2019 Nov 21;381[21]:1995-2008).

The performance of these two SGLT2 inhibitors was “incredibly consistent” across the their respective trials run in HFrEF patients with and without type 2 diabetes, and the combined evidence base of the two trials makes for “really compelling evidence” of both safety and efficacy that should prompt a change to U.S. practice, with both of these drugs forming a new cornerstone of HFrEF treatment, Dr. Packer said.
 

Results plant drug class firmly as HFrEF treatment

Dr. Packer stressed in his presentation that optimal treatment of patients with HFrEF now demands use of one of these two SGLT2 inhibitors, as well as sacubitril plus valsartan (Entresto), a beta-blocker, and a mineralocorticoid receptor antagonist, plus a diuretic as a fifth drug class for the many HFrEF patients who also need treatment for fluid overload. He further advocated for rapid introduction of these four cornerstone agents with proven survival benefits once a patient receives a HFrEF diagnosis, suggesting that sacubitril plus valsartan, an SGLT2 inhibitor, a beta-blocker, and a mineralocorticoid receptor antagonist could all be initiated within 6 weeks or less while acknowledging that optimal up-titration of the beta-blocker would likely take longer.

The order in which a patient starts these drugs shouldn’t matter, and there currently seems to be no evidence that clearly points toward using either dapagliflozin or empagliflozin over the other, Dr. Packer added.

In recognition of the importance of sending a message to heart failure clinicians about the newly proven efficacy of SGLT2 inhibitors in HFrEF patients, the American College of Cardiology and American Heart Association are now drafting an “expert decision pathway” to help clinicians as they enter this new prescribing space. This interim guidance should come out before the end of 2020, prior to release of fully revised HFrEF management guidelines in 2021, said Athena Poppas, MD, president of the ACC, in an interview.

“There is clearly need for education” that can help guide physicians who care for HFrEF patients on how to introduce an SGLT2 inhibitor along with the additional, lengthy list of drug classes proven to benefit these patients, noted Dr. Poppas, who is also a professor and chief of cardiology at the Brown University in Providence, R.I. Physicians may find that they need extra backup for successfully starting both sacubitril plus valsartan and an SGLT2 inhibitor in HFrEF patients because recent history has shown substantial pushback from third-party payers in reimbursing for these relatively expensive drugs, Dr. Poppas noted. She added that this is a problem that may be compounded when patients should ideally get both drug classes.

Physicians who care for heart failure patients have their own history of dragging their feet when adding new drugs to the regimens HFrEF patients receive. The angiotensin converting enzyme inhibitors and beta-blockers took about 17 years each to start reaching a majority of U.S. HFrEF patients, and sacubitril plus valsartan is now used on perhaps a quarter to a third of HFrEF patients despite receiving Food and Drug Administration approval for these patients in mid 2015, noted Christopher M. O’Connor, MD, a heart failure specialist and president of the Inova Heart and Vascular Institute in Fairfax, Va.

Despite dapagliflozin receiving FDA approval in May 2020 for treating HFrEF in patients without diabetes, early uptake in U.S. practice has been very slow, with findings from large U.S. patient registries suggesting that perhaps 1% of suitable HFrEF patients currently get the drug, estimated Dr. O’Connor in an interview.

Given how strong the evidence now is for benefit and safety from dapagliflozin and empagliflozin, it may take as little as 5 years to reach greater than 50% penetration of one of these drugs into U.S. HFrEF patient populations, suggested Dr. Packer, a distinguished scholar in cardiovascular science at Baylor University Medical Center in Dallas.
 

EMPEROR-Reduced outcomes

The road to routine use of these SGLT2 inhibitor drugs should be hastened by empagliflozin’s impressive performance in EMPEROR-Reduced, in which the drug scored highly significant benefits over placebo for the prespecified primary and two major secondary endpoints, one of which was a measure of preserved renal function.

The trial randomized 3,730 patients at 520 sites in 20 countries during 2017-2019 and followed them on treatment for a median of 16 months. All patients had a left ventricular ejection fraction of 40% or less, and roughly three-quarters had New York Heart Association (NYHA) class II function, nearly one-quarter had class III function, and fewer than 1% of patients fell into the class IV category.

The primary endpoint occurred in 19% of the empagliflozin-treated patients and in 25% of those who received placebo. Among the half of patients with diabetes in the trial, the relative risk reduction by empagliflozin compared with placebo was a statistically significant 28%; among those without diabetes, it was a statistically significant 22%. Concurrently with Dr. Packer’s report, the results appeared in an article posted online (N Engl J Med. 2020 Aug 29. doi: 10.1056/NEJMoa2022190).

The study also had two main prespecified secondary endpoints: the incidence of total hospitalizations for heart failure, both first and recurrent, which fell by 30% in the empagliflozin-treated patients, compared with placebo, and the rate of declining renal function during the 16 months of the study as measured by estimated glomerular filtration rate, which dropped by roughly 1 mL/min per 1.73 m² among the empagliflozin recipients and by about 4 mL/min/ per 1.73 m² in the placebo patients.

Treatment with empagliflozin also achieved a notable, statistically significant 50% drop in major adverse renal events, consistent with the performance of other drugs in the class.

“Renal protection is a big plus” of empagliflozin in this trial and from the other SGLT2 inhibitors in prior studies, noted Dr. O’Connor.

The EMPEROR-Reduced results also showed an important benefit for HFrEF patients from empagliflozin not previously seen as quickly with any other drug class, noted Dr. Packer. The SGLT2 inhibitor led to statistically a significant slowing in the progression of patients from NYHA class II function to class III, compared with placebo, and it also significantly promoted the recovery of patients from NYHA class III to class II, an effect that became apparent within the first month on treatment and a benefit that is a “big deal” for patients because it represents a “significant change in functional capacity.” This additional dimension of empagliflozin’s benefit “really impressed me,” Dr. Packer said.

EMPEROR-Reduced was funded by Boehringer Ingelheim and Eli Lilly, the companies that market empagliflozin. Dr. Packer has received personal fees from Boehringer Ingelheim and Eli Lilly and from several other companies. Dr. Poppas and Dr. O’Connor had no relevant disclosures.
 

[email protected]

SOURCE: Packer M. ESC 2020. N Engl J Med. 2020 Aug 29. doi: 10.1056/NEJMoa2022190.

Initiation of rhythm control with antiarrhythmic drugs and/or ablation in patients with early, recently diagnosed atrial fibrillation (AFib) led to a significantly lower risk of major adverse cardiovascular outcomes, compared with a rate-control strategy, during more than 5 years of follow-up in the large randomized EAST-AFNET 4 trial, Paulus Kirchhof, MD, said at the virtual annual congress of the European Society of Cardiology.

Previous trials of rate versus rhythm control in AFib, such as AFFIRM (Atrial Fibrillation Follow-up Investigation of Rhythm Management), failed to show an advantage for rhythm over rate control in terms of clinical outcomes. Why was EAST-AFNET 4 different? Dr. Kirchhof offered two major reasons: The study incorporated AFib ablation as an option in the rhythm control strategy, and treatment started soon after diagnosis of the arrhythmia. Indeed, nearly 40% of patients had their first-ever AFib episode at the time of randomization, and the median time from diagnosis to randomization was just 36 days.

“Once you are in AFib for a few months, the atrium suffers severe damage, some of it irreversible, so it becomes more difficult to restore and maintain sinus rhythm when you wait longer,” explained Dr. Kirchhof, director of the department of cardiology at the University Heart and Vascular Center in Hamburg (Ger.) and professor of cardiovascular medicine at the University of Birmingham, England.

Also, epidemiologic studies show that the risk of cardiovascular complications is heightened in the first year following diagnosis of AFib. “So there’s a window of opportunity to prevent complications,” he added.

The impetus for conducting EAST-AFNET 4 (Early Treatment of Atrial Fibrillation for Stroke Prevention Trial ) was straightforward, according to the cardiologist: “The question of whether rhythm control is beneficial or not has been in the field for several decades. Most people, like me, always believed that maintaining sinus rhythm would help, but we didn’t have the data to show it.”
 

Early rhythm control shows sustained benefits

EAST-AFNET 4 was a prospective, open, blinded-outcome-assessement trial. It included 2,789 patients with early AFib and an average CHA₂DS₂-VASc score of 3.4 who were randomized at 135 sites in 11 European countries to early rhythm control or guideline-recommended rate control. At a median 5.1 years of follow-up, the primary outcome – a composite of cardiovascular death, stroke, acute coronary syndrome, or hospitalization for worsening heart failure – occurred at a pace of 3.9% per year in the rhythm control group and 5% per year with rate control. This translated to a statistically significant and clinically meaningful 21% relative risk reduction favoring early rhythm control.

The 28% reduction in cardiovascular death with rhythm control was statistically significant, as was the 35% reduction in stroke. However, the 19% reduction in heart failure hospitalizations and 17% decrease in hospitalizations for acute coronary syndrome were not.

The co–primary endpoint – the mean number of nights spent in the hospital per year, which served as a proxy for the cost of treatment to a health care system – didn’t differ between the two treatment arms, at roughly 5 nights per year.

The clinical benefit of early rhythm control was consistent across all 19 prespecified patient subgroups, including those who were asymptomatic and patients with or without heart failure.

Serious adverse events related to rhythm control therapy – most often drug-related bradycardia – occurred in 4.9% of patients over the course of 5.1 years, compared to a 1.4% serious event rate in patients assigned to rate control. Dr. Kirchhof called the roughly 1% per year serious event rate in the rhythm control group quite acceptable.

“To put that in perspective, the annualized rate of severe bleeds on oral anticoagulation – a very beneficial therapy used by more than 90% of participants at 2 years – is about 2%,” the cardiologist noted.

Only 8% of patients randomized to rhythm control received AFib ablation as initial therapy, consistent with current clinical practice. By 2 years, 19.4% of the rhythm control group had undergone AFib ablation. Also at that time, 15% of the rate control group was receiving rhythm control therapy to help manage AFib-related symptoms.

One of the big surprises in the study, he said, was that nearly three-quarters of patients in both groups were asymptomatic at 2 years.

“I think that shows how well we control symptoms, even without rhythm control,” he observed.
 

Results ‘move the field forward’

Dr. Kirchhof stressed that this was a trial of two different treatment strategies, and it’s not yet possible to single out any specific component of the rhythm control strategy as being responsible for the improved outcomes.

“I cannot tell you whether the outcome difference was due to AFib ablation or early treatment or the fact that we’re now better at using antiarrhythmic drugs than we were 20 years ago,” he said.

Asked if the EAST-AFNET 4 findings warrant more aggressive screening for AFib in order to detect and intervene early in the arrhythmia, Dr. Kirchhof replied with an unambiguous yes.

“My conclusion is that every patient with newly diagnosed AFib and a CHA₂DS₂-VASc score of 2 or more should not only receive anticoagulation and rate control, but should also be offered rhythm control therapy at the time of diagnosis, which also means that all of these people have to be seen by a cardiologist who has expertise in the domain of AFib management. It’s a big clinical challenge, but it leads to a 21% improvement in outcomes, and I think we have to do what’s best for our patients,” he said.

In an interview, Kalyanam Shivkumar, MD, PhD, called EAST-AFNET 4 “a very important study.”

“It moves the field forward, for sure. I think it will change clinical practice, and it should,” commented Dr. Shivkumar, who was not involved in the study.

“Now there are so many wearable technologies out there – the Apple Watch and others – which will enable rhythm abnormalities to be detected early on. This bodes well for the field,” said Dr. Shivkumar, who is editor-in-chief of JACC: Clinical Electrophysiology. He is also professor of medicine, radiology, and bioengineering at the University of California, Los Angeles, and director of the UCLA Cardiac Arrhythmia Center.

Dr. Kirchhof reported receiving research grants to conduct the EAST-AFNET 4 trial from the German Ministry of Education and Research, the German Center for Cardiovascular Research, the Atrial Fibrillation Network, the European Heart Rhythm Association, St. Jude Medical, Abbott, Sanofi, the German Heart Foundation, the European Union, the British Heart Foundation, and the Leducq Foundation.

Simultaneous with his presentation at ESC Congress 2020, the study results were published online at NEJM.org.
 

[email protected]

SOURCE: Kirchhof P. ESC Congress 2020. N Engl J Med. 2020 Aug 29. doi: 10.1056/NEJMoa2019422.

Initiation of rhythm control with antiarrhythmic drugs and/or ablation in patients with early, recently diagnosed atrial fibrillation (AFib) led to a significantly lower risk of major adverse cardiovascular outcomes, compared with a rate-control strategy, during more than 5 years of follow-up in the large randomized EAST-AFNET 4 trial, Paulus Kirchhof, MD, said at the virtual annual congress of the European Society of Cardiology.

Previous trials of rate versus rhythm control in AFib, such as AFFIRM (Atrial Fibrillation Follow-up Investigation of Rhythm Management), failed to show an advantage for rhythm over rate control in terms of clinical outcomes. Why was EAST-AFNET 4 different? Dr. Kirchhof offered two major reasons: The study incorporated AFib ablation as an option in the rhythm control strategy, and treatment started soon after diagnosis of the arrhythmia. Indeed, nearly 40% of patients had their first-ever AFib episode at the time of randomization, and the median time from diagnosis to randomization was just 36 days.

“Once you are in AFib for a few months, the atrium suffers severe damage, some of it irreversible, so it becomes more difficult to restore and maintain sinus rhythm when you wait longer,” explained Dr. Kirchhof, director of the department of cardiology at the University Heart and Vascular Center in Hamburg (Ger.) and professor of cardiovascular medicine at the University of Birmingham, England.

Also, epidemiologic studies show that the risk of cardiovascular complications is heightened in the first year following diagnosis of AFib. “So there’s a window of opportunity to prevent complications,” he added.

The impetus for conducting EAST-AFNET 4 (Early Treatment of Atrial Fibrillation for Stroke Prevention Trial ) was straightforward, according to the cardiologist: “The question of whether rhythm control is beneficial or not has been in the field for several decades. Most people, like me, always believed that maintaining sinus rhythm would help, but we didn’t have the data to show it.”
 

Early rhythm control shows sustained benefits

EAST-AFNET 4 was a prospective, open, blinded-outcome-assessement trial. It included 2,789 patients with early AFib and an average CHA₂DS₂-VASc score of 3.4 who were randomized at 135 sites in 11 European countries to early rhythm control or guideline-recommended rate control. At a median 5.1 years of follow-up, the primary outcome – a composite of cardiovascular death, stroke, acute coronary syndrome, or hospitalization for worsening heart failure – occurred at a pace of 3.9% per year in the rhythm control group and 5% per year with rate control. This translated to a statistically significant and clinically meaningful 21% relative risk reduction favoring early rhythm control.

The 28% reduction in cardiovascular death with rhythm control was statistically significant, as was the 35% reduction in stroke. However, the 19% reduction in heart failure hospitalizations and 17% decrease in hospitalizations for acute coronary syndrome were not.

The co–primary endpoint – the mean number of nights spent in the hospital per year, which served as a proxy for the cost of treatment to a health care system – didn’t differ between the two treatment arms, at roughly 5 nights per year.

The clinical benefit of early rhythm control was consistent across all 19 prespecified patient subgroups, including those who were asymptomatic and patients with or without heart failure.

Serious adverse events related to rhythm control therapy – most often drug-related bradycardia – occurred in 4.9% of patients over the course of 5.1 years, compared to a 1.4% serious event rate in patients assigned to rate control. Dr. Kirchhof called the roughly 1% per year serious event rate in the rhythm control group quite acceptable.

“To put that in perspective, the annualized rate of severe bleeds on oral anticoagulation – a very beneficial therapy used by more than 90% of participants at 2 years – is about 2%,” the cardiologist noted.

Only 8% of patients randomized to rhythm control received AFib ablation as initial therapy, consistent with current clinical practice. By 2 years, 19.4% of the rhythm control group had undergone AFib ablation. Also at that time, 15% of the rate control group was receiving rhythm control therapy to help manage AFib-related symptoms.

One of the big surprises in the study, he said, was that nearly three-quarters of patients in both groups were asymptomatic at 2 years.

“I think that shows how well we control symptoms, even without rhythm control,” he observed.
 

Results ‘move the field forward’

Dr. Kirchhof stressed that this was a trial of two different treatment strategies, and it’s not yet possible to single out any specific component of the rhythm control strategy as being responsible for the improved outcomes.

“I cannot tell you whether the outcome difference was due to AFib ablation or early treatment or the fact that we’re now better at using antiarrhythmic drugs than we were 20 years ago,” he said.

Asked if the EAST-AFNET 4 findings warrant more aggressive screening for AFib in order to detect and intervene early in the arrhythmia, Dr. Kirchhof replied with an unambiguous yes.

“My conclusion is that every patient with newly diagnosed AFib and a CHA₂DS₂-VASc score of 2 or more should not only receive anticoagulation and rate control, but should also be offered rhythm control therapy at the time of diagnosis, which also means that all of these people have to be seen by a cardiologist who has expertise in the domain of AFib management. It’s a big clinical challenge, but it leads to a 21% improvement in outcomes, and I think we have to do what’s best for our patients,” he said.

In an interview, Kalyanam Shivkumar, MD, PhD, called EAST-AFNET 4 “a very important study.”

“It moves the field forward, for sure. I think it will change clinical practice, and it should,” commented Dr. Shivkumar, who was not involved in the study.

“Now there are so many wearable technologies out there – the Apple Watch and others – which will enable rhythm abnormalities to be detected early on. This bodes well for the field,” said Dr. Shivkumar, who is editor-in-chief of JACC: Clinical Electrophysiology. He is also professor of medicine, radiology, and bioengineering at the University of California, Los Angeles, and director of the UCLA Cardiac Arrhythmia Center.

Dr. Kirchhof reported receiving research grants to conduct the EAST-AFNET 4 trial from the German Ministry of Education and Research, the German Center for Cardiovascular Research, the Atrial Fibrillation Network, the European Heart Rhythm Association, St. Jude Medical, Abbott, Sanofi, the German Heart Foundation, the European Union, the British Heart Foundation, and the Leducq Foundation.

Simultaneous with his presentation at ESC Congress 2020, the study results were published online at NEJM.org.
 

[email protected]

SOURCE: Kirchhof P. ESC Congress 2020. N Engl J Med. 2020 Aug 29. doi: 10.1056/NEJMoa2019422.

Initiation of rhythm control with antiarrhythmic drugs and/or ablation in patients with early, recently diagnosed atrial fibrillation (AFib) led to a significantly lower risk of major adverse cardiovascular outcomes, compared with a rate-control strategy, during more than 5 years of follow-up in the large randomized EAST-AFNET 4 trial, Paulus Kirchhof, MD, said at the virtual annual congress of the European Society of Cardiology.

Previous trials of rate versus rhythm control in AFib, such as AFFIRM (Atrial Fibrillation Follow-up Investigation of Rhythm Management), failed to show an advantage for rhythm over rate control in terms of clinical outcomes. Why was EAST-AFNET 4 different? Dr. Kirchhof offered two major reasons: The study incorporated AFib ablation as an option in the rhythm control strategy, and treatment started soon after diagnosis of the arrhythmia. Indeed, nearly 40% of patients had their first-ever AFib episode at the time of randomization, and the median time from diagnosis to randomization was just 36 days.

“Once you are in AFib for a few months, the atrium suffers severe damage, some of it irreversible, so it becomes more difficult to restore and maintain sinus rhythm when you wait longer,” explained Dr. Kirchhof, director of the department of cardiology at the University Heart and Vascular Center in Hamburg (Ger.) and professor of cardiovascular medicine at the University of Birmingham, England.

Also, epidemiologic studies show that the risk of cardiovascular complications is heightened in the first year following diagnosis of AFib. “So there’s a window of opportunity to prevent complications,” he added.

The impetus for conducting EAST-AFNET 4 (Early Treatment of Atrial Fibrillation for Stroke Prevention Trial ) was straightforward, according to the cardiologist: “The question of whether rhythm control is beneficial or not has been in the field for several decades. Most people, like me, always believed that maintaining sinus rhythm would help, but we didn’t have the data to show it.”
 

Early rhythm control shows sustained benefits

EAST-AFNET 4 was a prospective, open, blinded-outcome-assessement trial. It included 2,789 patients with early AFib and an average CHA₂DS₂-VASc score of 3.4 who were randomized at 135 sites in 11 European countries to early rhythm control or guideline-recommended rate control. At a median 5.1 years of follow-up, the primary outcome – a composite of cardiovascular death, stroke, acute coronary syndrome, or hospitalization for worsening heart failure – occurred at a pace of 3.9% per year in the rhythm control group and 5% per year with rate control. This translated to a statistically significant and clinically meaningful 21% relative risk reduction favoring early rhythm control.

The 28% reduction in cardiovascular death with rhythm control was statistically significant, as was the 35% reduction in stroke. However, the 19% reduction in heart failure hospitalizations and 17% decrease in hospitalizations for acute coronary syndrome were not.

The co–primary endpoint – the mean number of nights spent in the hospital per year, which served as a proxy for the cost of treatment to a health care system – didn’t differ between the two treatment arms, at roughly 5 nights per year.

The clinical benefit of early rhythm control was consistent across all 19 prespecified patient subgroups, including those who were asymptomatic and patients with or without heart failure.

Serious adverse events related to rhythm control therapy – most often drug-related bradycardia – occurred in 4.9% of patients over the course of 5.1 years, compared to a 1.4% serious event rate in patients assigned to rate control. Dr. Kirchhof called the roughly 1% per year serious event rate in the rhythm control group quite acceptable.

“To put that in perspective, the annualized rate of severe bleeds on oral anticoagulation – a very beneficial therapy used by more than 90% of participants at 2 years – is about 2%,” the cardiologist noted.

Only 8% of patients randomized to rhythm control received AFib ablation as initial therapy, consistent with current clinical practice. By 2 years, 19.4% of the rhythm control group had undergone AFib ablation. Also at that time, 15% of the rate control group was receiving rhythm control therapy to help manage AFib-related symptoms.

One of the big surprises in the study, he said, was that nearly three-quarters of patients in both groups were asymptomatic at 2 years.

“I think that shows how well we control symptoms, even without rhythm control,” he observed.
 

Results ‘move the field forward’

Dr. Kirchhof stressed that this was a trial of two different treatment strategies, and it’s not yet possible to single out any specific component of the rhythm control strategy as being responsible for the improved outcomes.

“I cannot tell you whether the outcome difference was due to AFib ablation or early treatment or the fact that we’re now better at using antiarrhythmic drugs than we were 20 years ago,” he said.

Asked if the EAST-AFNET 4 findings warrant more aggressive screening for AFib in order to detect and intervene early in the arrhythmia, Dr. Kirchhof replied with an unambiguous yes.

“My conclusion is that every patient with newly diagnosed AFib and a CHA₂DS₂-VASc score of 2 or more should not only receive anticoagulation and rate control, but should also be offered rhythm control therapy at the time of diagnosis, which also means that all of these people have to be seen by a cardiologist who has expertise in the domain of AFib management. It’s a big clinical challenge, but it leads to a 21% improvement in outcomes, and I think we have to do what’s best for our patients,” he said.

In an interview, Kalyanam Shivkumar, MD, PhD, called EAST-AFNET 4 “a very important study.”

“It moves the field forward, for sure. I think it will change clinical practice, and it should,” commented Dr. Shivkumar, who was not involved in the study.

“Now there are so many wearable technologies out there – the Apple Watch and others – which will enable rhythm abnormalities to be detected early on. This bodes well for the field,” said Dr. Shivkumar, who is editor-in-chief of JACC: Clinical Electrophysiology. He is also professor of medicine, radiology, and bioengineering at the University of California, Los Angeles, and director of the UCLA Cardiac Arrhythmia Center.

Dr. Kirchhof reported receiving research grants to conduct the EAST-AFNET 4 trial from the German Ministry of Education and Research, the German Center for Cardiovascular Research, the Atrial Fibrillation Network, the European Heart Rhythm Association, St. Jude Medical, Abbott, Sanofi, the German Heart Foundation, the European Union, the British Heart Foundation, and the Leducq Foundation.

Simultaneous with his presentation at ESC Congress 2020, the study results were published online at NEJM.org.
 

[email protected]

SOURCE: Kirchhof P. ESC Congress 2020. N Engl J Med. 2020 Aug 29. doi: 10.1056/NEJMoa2019422.

The mortality burden associated with dementia may be 2.7 times greater than estimated, according to an analysis of a prospective cohort study. This burden may be greatest among non-Hispanic black older adults, compared with Hispanic and non-Hispanic whites. This burden also is significantly greater among people with less than a high school education, compared with those with a college education.

The study results underscore the importance of broadening access to population-based interventions that focus on dementia prevention and care, the investigators wrote. “Future research could examine the extent to which deaths attributable to dementia and underestimation of dementia as an underlying cause of death on death certificates might have changed over time,” wrote Andrew C. Stokes, PhD, assistant professor of global health at the Boston University School of Public Health, and colleagues.

The study was published online Aug. 24 in JAMA Neurology.

In 2019, approximately 5.6 million adults in the United States who were aged 65 years or older had Alzheimer’s disease, vascular dementia, or mixed-cause dementia. A further 18.8% of Americans in this age group had cognitive impairment without dementia (CIND). About one third of patients with CIND may develop Alzheimer’s disease or related dementias (ADRD) within 5 years.

Research suggests that medical examiners significantly underreport ADRD on death certificates. One community-based study, for example, found that only 25% of deaths in patients with dementia had Alzheimer’s disease listed on the death certificates. Other research found that deaths in patients with dementia were often coded using more proximate causes, such as cardiovascular disease, sepsis, and pneumonia.
 

Health and retirement study

Dr. Stokes and colleagues examined data from the Health and Retirement Study (HRS) to evaluate the association of dementia and CIND with all-cause mortality. The HRS is a longitudinal cohort study of adults older than 50 years who live in the community. Its sample is nationally representative. The HRS investigators also initiated the Aging, Demographics, and Memory study to develop a procedure for assessing cognitive status in the HRS sample.

In their study, Dr. Stokes and colleagues included adults who had been sampled in the 2000 wave of HRS. They focused on participants between ages 70 and 99 years at baseline, and their final sample included 7,342 older adults. To identify dementia status, the researchers used the Langa–Weir score cutoff, which is based on tests of immediate and delayed recall of 10 words, a serial 7-second task, and a backward counting task. They also classified dementia status using the Herzog–Wallace, Wu, Hurd, and modified Hurd algorithms.

At baseline, the researchers measured age, sex, race or ethnicity, educational attainment, smoking status, self-reported disease diagnoses, and U.S. Census division as covariates. The National Center for Health Statistics linked HRS data with National Death Index records. These linked records include underlying cause of death and any mention of a condition or cause of death on the death certificate. The researchers compared the percentage of deaths attributable to ADRD according to a population attributable fraction estimate with the proportion of dementia-related deaths according to underlying causes and with any mention of dementia on death certificates.

The sample of 7,342 older adults included 4,348 (60.3%) women. Data for 1,030 (13.4%) people were reported by proxy. At baseline, most participants (64.0%) were between ages 70 and 79 years, 31% were between ages 80 and 89, and 5% were between ages 90 and 99 years. The prevalence of dementia in the complete sample was 14.3%, and the prevalence of CIND was 24.7%. The prevalence of dementia (22.4%) and CIND (29.3%) was higher among decedents than among the full population.

The hazard ratio (HR) for mortality was 2.53 among participants with dementia and 1.53 among patients with CIND. Although 13.6% of deaths were attributable to dementia, the proportion of deaths assigned to dementia as an underlying cause on death certificates was 5.0%. This discrepancy suggests that dementia is underreported by more than a factor of 2.7.

The mortality burden of dementia was 24.7% in non-Hispanic black older adults, 20.7% in Hispanic white participants, and 12.2% in non-Hispanic white participants. In addition, the mortality burden of dementia was significantly greater among participants with less than a high school education (16.2%) than among participants with a college education (9.8%).

The degree to which the underlying cause of death underestimated the mortality burden of dementia varied by sociodemographic characteristics, health status, and geography. The burden was underestimated by a factor of 7.1 among non-Hispanic black participants, a factor of 4.1 among Hispanic participants, and a factor of 2.3 among non-Hispanic white participants. The burden was underestimated by a factor of 3.5 in men and a factor of 2.4 in women. In addition, the burden was underestimated by a factor of 3.0 among participants with less than a high school education, by a factor of 2.3 among participants with a high school education, by a factor of 1.9 in participants with some college, and by a factor of 2.5 among participants with a college or higher education.

One of the study’s strengths was its population attributable fraction analysis, which reduced the risk of overestimating the mortality burden of dementia, Dr. Stokes and colleagues wrote. Examining CIND is valuable because of its high prevalence and consequent influence on outcomes in the population, even though CIND is associated with a lower mortality risk, they added. Nevertheless, the investigators were unable to assess mortality for dementia subtypes, and the classifications of dementia status and CIND may be subject to measurement error.
 

Underestimation is systematic

“This study is eye-opening in that it highlights the systematic underestimation of deaths attributable to dementia,” said Costantino Iadecola, MD, Anne Parrish Titzell professor of neurology and director and chair of the Feil Family Brain and Mind Research Institute at Weill Cornell Medicine in New York. The study’s main strength is that it is nationally representative, but the data must be confirmed in a larger population, he added.

The results will clarify the effect of dementia on mortality for neurologists, and geriatricians should be made aware of them, said Dr. Iadecola. “These data should be valuable to rationalize public health efforts and related funding decisions concerning research and community support.”

Further research could determine the mortality of dementia subgroups, “especially dementias linked to vascular factors in which prevention may be effective,” said Dr. Iadecola. “In the older population, vascular factors may play a more preeminent role, and it may help focus preventive approaches.”

The study was supported by a grant from the National Institute on Aging. Dr. Stokes received grants from Ethicon that were unrelated to this study. Dr. Iadecola serves on the scientific advisory board of Broadview Venture.

[email protected]

SOURCE: Stokes AC et al. JAMA Neurol. 2020 Aug 24. doi: 10.1001/jamaneurol.2020.2831.

The mortality burden associated with dementia may be 2.7 times greater than estimated, according to an analysis of a prospective cohort study. This burden may be greatest among non-Hispanic black older adults, compared with Hispanic and non-Hispanic whites. This burden also is significantly greater among people with less than a high school education, compared with those with a college education.

The study results underscore the importance of broadening access to population-based interventions that focus on dementia prevention and care, the investigators wrote. “Future research could examine the extent to which deaths attributable to dementia and underestimation of dementia as an underlying cause of death on death certificates might have changed over time,” wrote Andrew C. Stokes, PhD, assistant professor of global health at the Boston University School of Public Health, and colleagues.

The study was published online Aug. 24 in JAMA Neurology.

In 2019, approximately 5.6 million adults in the United States who were aged 65 years or older had Alzheimer’s disease, vascular dementia, or mixed-cause dementia. A further 18.8% of Americans in this age group had cognitive impairment without dementia (CIND). About one third of patients with CIND may develop Alzheimer’s disease or related dementias (ADRD) within 5 years.

Research suggests that medical examiners significantly underreport ADRD on death certificates. One community-based study, for example, found that only 25% of deaths in patients with dementia had Alzheimer’s disease listed on the death certificates. Other research found that deaths in patients with dementia were often coded using more proximate causes, such as cardiovascular disease, sepsis, and pneumonia.
 

Health and retirement study

Dr. Stokes and colleagues examined data from the Health and Retirement Study (HRS) to evaluate the association of dementia and CIND with all-cause mortality. The HRS is a longitudinal cohort study of adults older than 50 years who live in the community. Its sample is nationally representative. The HRS investigators also initiated the Aging, Demographics, and Memory study to develop a procedure for assessing cognitive status in the HRS sample.

In their study, Dr. Stokes and colleagues included adults who had been sampled in the 2000 wave of HRS. They focused on participants between ages 70 and 99 years at baseline, and their final sample included 7,342 older adults. To identify dementia status, the researchers used the Langa–Weir score cutoff, which is based on tests of immediate and delayed recall of 10 words, a serial 7-second task, and a backward counting task. They also classified dementia status using the Herzog–Wallace, Wu, Hurd, and modified Hurd algorithms.

At baseline, the researchers measured age, sex, race or ethnicity, educational attainment, smoking status, self-reported disease diagnoses, and U.S. Census division as covariates. The National Center for Health Statistics linked HRS data with National Death Index records. These linked records include underlying cause of death and any mention of a condition or cause of death on the death certificate. The researchers compared the percentage of deaths attributable to ADRD according to a population attributable fraction estimate with the proportion of dementia-related deaths according to underlying causes and with any mention of dementia on death certificates.

The sample of 7,342 older adults included 4,348 (60.3%) women. Data for 1,030 (13.4%) people were reported by proxy. At baseline, most participants (64.0%) were between ages 70 and 79 years, 31% were between ages 80 and 89, and 5% were between ages 90 and 99 years. The prevalence of dementia in the complete sample was 14.3%, and the prevalence of CIND was 24.7%. The prevalence of dementia (22.4%) and CIND (29.3%) was higher among decedents than among the full population.

The hazard ratio (HR) for mortality was 2.53 among participants with dementia and 1.53 among patients with CIND. Although 13.6% of deaths were attributable to dementia, the proportion of deaths assigned to dementia as an underlying cause on death certificates was 5.0%. This discrepancy suggests that dementia is underreported by more than a factor of 2.7.

The mortality burden of dementia was 24.7% in non-Hispanic black older adults, 20.7% in Hispanic white participants, and 12.2% in non-Hispanic white participants. In addition, the mortality burden of dementia was significantly greater among participants with less than a high school education (16.2%) than among participants with a college education (9.8%).

The degree to which the underlying cause of death underestimated the mortality burden of dementia varied by sociodemographic characteristics, health status, and geography. The burden was underestimated by a factor of 7.1 among non-Hispanic black participants, a factor of 4.1 among Hispanic participants, and a factor of 2.3 among non-Hispanic white participants. The burden was underestimated by a factor of 3.5 in men and a factor of 2.4 in women. In addition, the burden was underestimated by a factor of 3.0 among participants with less than a high school education, by a factor of 2.3 among participants with a high school education, by a factor of 1.9 in participants with some college, and by a factor of 2.5 among participants with a college or higher education.

One of the study’s strengths was its population attributable fraction analysis, which reduced the risk of overestimating the mortality burden of dementia, Dr. Stokes and colleagues wrote. Examining CIND is valuable because of its high prevalence and consequent influence on outcomes in the population, even though CIND is associated with a lower mortality risk, they added. Nevertheless, the investigators were unable to assess mortality for dementia subtypes, and the classifications of dementia status and CIND may be subject to measurement error.
 

Underestimation is systematic

“This study is eye-opening in that it highlights the systematic underestimation of deaths attributable to dementia,” said Costantino Iadecola, MD, Anne Parrish Titzell professor of neurology and director and chair of the Feil Family Brain and Mind Research Institute at Weill Cornell Medicine in New York. The study’s main strength is that it is nationally representative, but the data must be confirmed in a larger population, he added.

The results will clarify the effect of dementia on mortality for neurologists, and geriatricians should be made aware of them, said Dr. Iadecola. “These data should be valuable to rationalize public health efforts and related funding decisions concerning research and community support.”

Further research could determine the mortality of dementia subgroups, “especially dementias linked to vascular factors in which prevention may be effective,” said Dr. Iadecola. “In the older population, vascular factors may play a more preeminent role, and it may help focus preventive approaches.”

The study was supported by a grant from the National Institute on Aging. Dr. Stokes received grants from Ethicon that were unrelated to this study. Dr. Iadecola serves on the scientific advisory board of Broadview Venture.

[email protected]

SOURCE: Stokes AC et al. JAMA Neurol. 2020 Aug 24. doi: 10.1001/jamaneurol.2020.2831.

The mortality burden associated with dementia may be 2.7 times greater than estimated, according to an analysis of a prospective cohort study. This burden may be greatest among non-Hispanic black older adults, compared with Hispanic and non-Hispanic whites. This burden also is significantly greater among people with less than a high school education, compared with those with a college education.

The study results underscore the importance of broadening access to population-based interventions that focus on dementia prevention and care, the investigators wrote. “Future research could examine the extent to which deaths attributable to dementia and underestimation of dementia as an underlying cause of death on death certificates might have changed over time,” wrote Andrew C. Stokes, PhD, assistant professor of global health at the Boston University School of Public Health, and colleagues.

The study was published online Aug. 24 in JAMA Neurology.

In 2019, approximately 5.6 million adults in the United States who were aged 65 years or older had Alzheimer’s disease, vascular dementia, or mixed-cause dementia. A further 18.8% of Americans in this age group had cognitive impairment without dementia (CIND). About one third of patients with CIND may develop Alzheimer’s disease or related dementias (ADRD) within 5 years.

Research suggests that medical examiners significantly underreport ADRD on death certificates. One community-based study, for example, found that only 25% of deaths in patients with dementia had Alzheimer’s disease listed on the death certificates. Other research found that deaths in patients with dementia were often coded using more proximate causes, such as cardiovascular disease, sepsis, and pneumonia.
 

Health and retirement study

Dr. Stokes and colleagues examined data from the Health and Retirement Study (HRS) to evaluate the association of dementia and CIND with all-cause mortality. The HRS is a longitudinal cohort study of adults older than 50 years who live in the community. Its sample is nationally representative. The HRS investigators also initiated the Aging, Demographics, and Memory study to develop a procedure for assessing cognitive status in the HRS sample.

In their study, Dr. Stokes and colleagues included adults who had been sampled in the 2000 wave of HRS. They focused on participants between ages 70 and 99 years at baseline, and their final sample included 7,342 older adults. To identify dementia status, the researchers used the Langa–Weir score cutoff, which is based on tests of immediate and delayed recall of 10 words, a serial 7-second task, and a backward counting task. They also classified dementia status using the Herzog–Wallace, Wu, Hurd, and modified Hurd algorithms.

At baseline, the researchers measured age, sex, race or ethnicity, educational attainment, smoking status, self-reported disease diagnoses, and U.S. Census division as covariates. The National Center for Health Statistics linked HRS data with National Death Index records. These linked records include underlying cause of death and any mention of a condition or cause of death on the death certificate. The researchers compared the percentage of deaths attributable to ADRD according to a population attributable fraction estimate with the proportion of dementia-related deaths according to underlying causes and with any mention of dementia on death certificates.

The sample of 7,342 older adults included 4,348 (60.3%) women. Data for 1,030 (13.4%) people were reported by proxy. At baseline, most participants (64.0%) were between ages 70 and 79 years, 31% were between ages 80 and 89, and 5% were between ages 90 and 99 years. The prevalence of dementia in the complete sample was 14.3%, and the prevalence of CIND was 24.7%. The prevalence of dementia (22.4%) and CIND (29.3%) was higher among decedents than among the full population.

The hazard ratio (HR) for mortality was 2.53 among participants with dementia and 1.53 among patients with CIND. Although 13.6% of deaths were attributable to dementia, the proportion of deaths assigned to dementia as an underlying cause on death certificates was 5.0%. This discrepancy suggests that dementia is underreported by more than a factor of 2.7.

The mortality burden of dementia was 24.7% in non-Hispanic black older adults, 20.7% in Hispanic white participants, and 12.2% in non-Hispanic white participants. In addition, the mortality burden of dementia was significantly greater among participants with less than a high school education (16.2%) than among participants with a college education (9.8%).

The degree to which the underlying cause of death underestimated the mortality burden of dementia varied by sociodemographic characteristics, health status, and geography. The burden was underestimated by a factor of 7.1 among non-Hispanic black participants, a factor of 4.1 among Hispanic participants, and a factor of 2.3 among non-Hispanic white participants. The burden was underestimated by a factor of 3.5 in men and a factor of 2.4 in women. In addition, the burden was underestimated by a factor of 3.0 among participants with less than a high school education, by a factor of 2.3 among participants with a high school education, by a factor of 1.9 in participants with some college, and by a factor of 2.5 among participants with a college or higher education.

One of the study’s strengths was its population attributable fraction analysis, which reduced the risk of overestimating the mortality burden of dementia, Dr. Stokes and colleagues wrote. Examining CIND is valuable because of its high prevalence and consequent influence on outcomes in the population, even though CIND is associated with a lower mortality risk, they added. Nevertheless, the investigators were unable to assess mortality for dementia subtypes, and the classifications of dementia status and CIND may be subject to measurement error.
 

Underestimation is systematic

“This study is eye-opening in that it highlights the systematic underestimation of deaths attributable to dementia,” said Costantino Iadecola, MD, Anne Parrish Titzell professor of neurology and director and chair of the Feil Family Brain and Mind Research Institute at Weill Cornell Medicine in New York. The study’s main strength is that it is nationally representative, but the data must be confirmed in a larger population, he added.

The results will clarify the effect of dementia on mortality for neurologists, and geriatricians should be made aware of them, said Dr. Iadecola. “These data should be valuable to rationalize public health efforts and related funding decisions concerning research and community support.”

Further research could determine the mortality of dementia subgroups, “especially dementias linked to vascular factors in which prevention may be effective,” said Dr. Iadecola. “In the older population, vascular factors may play a more preeminent role, and it may help focus preventive approaches.”

The study was supported by a grant from the National Institute on Aging. Dr. Stokes received grants from Ethicon that were unrelated to this study. Dr. Iadecola serves on the scientific advisory board of Broadview Venture.

[email protected]

SOURCE: Stokes AC et al. JAMA Neurol. 2020 Aug 24. doi: 10.1001/jamaneurol.2020.2831.

American Indian/Alaska Native high school students are almost three times more likely to attempt suicide than high schoolers as a whole, according to newly released data from the 2019 Youth Risk Behavior Survey.

The prevalence of attempted suicide during the previous 12 months was 8.9% among the 13,677 students in grades 9-12 who took the survey last year, but the rate was 25.5% for American Indian/Alaska Native (AI/AN) respondents, almost 2.9 times higher, the YRBS data show.

Respondents with multiple races in their backgrounds, at 12.9%, and African Americans, with a prevalence of 11.8%, also were above the high school average for suicide attempts, while Whites (7.9%) and Asians (7.7%) were under it and Hispanics equaled it, the Centers for Disease Control and Prevention reported.

The number of AI/AN students was insufficient to examine differences by sex, but females in all of the other racial/ethnic groups were more likely than males to have attempted suicide: multiple race (17.8% vs. 7.3%), African American (15.2% vs. 8.5%), Hispanic (11.9% vs. 5.5%), White (9.4% vs. 6.4%), and Asian (8.4% vs. 7.1%), the CDC’s Division of Adolescent and School Health said.

Among all respondents, 11.0% of females had attempted suicide in the 12 months before the survey, a figure that is significantly higher than the 6.6% prevalence in males. Females also were significantly more likely than males to make a plan about how they would attempt suicide (19.9% vs. 11.3%) and to seriously consider an attempt (24.1% vs. 13.3%), CDC investigators said in a separate report.

Significant differences also were seen when looking at sexual identity. Suicide attempts were reported by 6.4% of heterosexuals, 16.1% of those who weren’t sure, and 23.4% of lesbians/gays/bisexuals (LGBs). For serious consideration of suicide, the respective numbers were 14.5%, 30.4%, and 46.8%, they reported (MMWR Supp. 2020 Aug 21;69[1]:47-55).

For nonheterosexuals, however, males were slightly more likely (23.8%) than females (23.6%) to have attempted suicide, but females were more likely to seriously consider it (49.0% vs. 40.4%) and to make a plan (42.4% vs. 33.0%), according to the YRBS data.

“Adolescence … represents a time for expanded identity development, with sexual identity development representing a complex, multidimensional, and often stressful process for youths,” the CDC investigators said in the MMWR. “To address the health differences in suicidal ideation and behaviors observed by student demographics and to decrease these outcomes overall, a comprehensive approach to suicide prevention, including programs, practices, and policies based on the best available evidence, is needed.”

[email protected]

American Indian/Alaska Native high school students are almost three times more likely to attempt suicide than high schoolers as a whole, according to newly released data from the 2019 Youth Risk Behavior Survey.

The prevalence of attempted suicide during the previous 12 months was 8.9% among the 13,677 students in grades 9-12 who took the survey last year, but the rate was 25.5% for American Indian/Alaska Native (AI/AN) respondents, almost 2.9 times higher, the YRBS data show.

Respondents with multiple races in their backgrounds, at 12.9%, and African Americans, with a prevalence of 11.8%, also were above the high school average for suicide attempts, while Whites (7.9%) and Asians (7.7%) were under it and Hispanics equaled it, the Centers for Disease Control and Prevention reported.

The number of AI/AN students was insufficient to examine differences by sex, but females in all of the other racial/ethnic groups were more likely than males to have attempted suicide: multiple race (17.8% vs. 7.3%), African American (15.2% vs. 8.5%), Hispanic (11.9% vs. 5.5%), White (9.4% vs. 6.4%), and Asian (8.4% vs. 7.1%), the CDC’s Division of Adolescent and School Health said.

Among all respondents, 11.0% of females had attempted suicide in the 12 months before the survey, a figure that is significantly higher than the 6.6% prevalence in males. Females also were significantly more likely than males to make a plan about how they would attempt suicide (19.9% vs. 11.3%) and to seriously consider an attempt (24.1% vs. 13.3%), CDC investigators said in a separate report.

Significant differences also were seen when looking at sexual identity. Suicide attempts were reported by 6.4% of heterosexuals, 16.1% of those who weren’t sure, and 23.4% of lesbians/gays/bisexuals (LGBs). For serious consideration of suicide, the respective numbers were 14.5%, 30.4%, and 46.8%, they reported (MMWR Supp. 2020 Aug 21;69[1]:47-55).

For nonheterosexuals, however, males were slightly more likely (23.8%) than females (23.6%) to have attempted suicide, but females were more likely to seriously consider it (49.0% vs. 40.4%) and to make a plan (42.4% vs. 33.0%), according to the YRBS data.

“Adolescence … represents a time for expanded identity development, with sexual identity development representing a complex, multidimensional, and often stressful process for youths,” the CDC investigators said in the MMWR. “To address the health differences in suicidal ideation and behaviors observed by student demographics and to decrease these outcomes overall, a comprehensive approach to suicide prevention, including programs, practices, and policies based on the best available evidence, is needed.”

[email protected]

American Indian/Alaska Native high school students are almost three times more likely to attempt suicide than high schoolers as a whole, according to newly released data from the 2019 Youth Risk Behavior Survey.

The prevalence of attempted suicide during the previous 12 months was 8.9% among the 13,677 students in grades 9-12 who took the survey last year, but the rate was 25.5% for American Indian/Alaska Native (AI/AN) respondents, almost 2.9 times higher, the YRBS data show.

Respondents with multiple races in their backgrounds, at 12.9%, and African Americans, with a prevalence of 11.8%, also were above the high school average for suicide attempts, while Whites (7.9%) and Asians (7.7%) were under it and Hispanics equaled it, the Centers for Disease Control and Prevention reported.

The number of AI/AN students was insufficient to examine differences by sex, but females in all of the other racial/ethnic groups were more likely than males to have attempted suicide: multiple race (17.8% vs. 7.3%), African American (15.2% vs. 8.5%), Hispanic (11.9% vs. 5.5%), White (9.4% vs. 6.4%), and Asian (8.4% vs. 7.1%), the CDC’s Division of Adolescent and School Health said.

Among all respondents, 11.0% of females had attempted suicide in the 12 months before the survey, a figure that is significantly higher than the 6.6% prevalence in males. Females also were significantly more likely than males to make a plan about how they would attempt suicide (19.9% vs. 11.3%) and to seriously consider an attempt (24.1% vs. 13.3%), CDC investigators said in a separate report.

Significant differences also were seen when looking at sexual identity. Suicide attempts were reported by 6.4% of heterosexuals, 16.1% of those who weren’t sure, and 23.4% of lesbians/gays/bisexuals (LGBs). For serious consideration of suicide, the respective numbers were 14.5%, 30.4%, and 46.8%, they reported (MMWR Supp. 2020 Aug 21;69[1]:47-55).

For nonheterosexuals, however, males were slightly more likely (23.8%) than females (23.6%) to have attempted suicide, but females were more likely to seriously consider it (49.0% vs. 40.4%) and to make a plan (42.4% vs. 33.0%), according to the YRBS data.

“Adolescence … represents a time for expanded identity development, with sexual identity development representing a complex, multidimensional, and often stressful process for youths,” the CDC investigators said in the MMWR. “To address the health differences in suicidal ideation and behaviors observed by student demographics and to decrease these outcomes overall, a comprehensive approach to suicide prevention, including programs, practices, and policies based on the best available evidence, is needed.”

[email protected]

The US Food and Drug Administration (FDA) has approved marketing of the first authorized diagnostic antigen test for SARS-CoV-2 that can be used without an analyzer.

Abbott

The BinaxNOW COVID-19 Ag Card (Abbott) is similar in some ways to a home pregnancy test. Clinicians read results on a card – one line for a negative result, two lines for positive.

A health care provider swabs a symptomatic patient’s nose, twirls the sample on a test card with a reagent, and waits approximately 15 minutes for results. No additional equipment is required.

Abbott expects the test to cost about $5.00, the company announced.

Office-based physicians, ED physicians, and school nurses could potentially use the product as a point-of-care test. The FDA granted the test emergency use authorization. It is approved for people suspected of having COVID-19 who are within 7 days of symptom onset.

“This new COVID-19 antigen test is an important addition to available tests because the results can be read in minutes, right off the testing card,” Jeff Shuren, MD, JD, director of the FDA’s Center for Devices and Radiological Health, wrote in a news release. “This means people will know if they have the virus in almost real time.”

“This fits into the testing landscape as a simple, inexpensive test that does not require additional equipment,” Marcus Lynch, PhD, assistant manager of the Health Care Horizon Scanning program at ECRI, told Medscape Medical News when asked to comment. ECRI is an independent, nonprofit organization that reviews and analyses COVID-19 therapeutics and diagnostics.

The test could help with early triage of patients who test positive, perhaps alerting physicians to the need to start COVID-19 therapy, added Lynch, who specializes in immunology and vaccine development. The test also could be useful in low-resource settings.

The FDA included a caveat: antigen tests are generally less sensitive than molecular assays. “Due to the potential for decreased sensitivity compared to molecular assays, negative results from an antigen test may need to be confirmed with a molecular test prior to making treatment decisions,” the agency noted.

Lynch agreed and said that when a patient tests negative, physicians still need to use their clinical judgment on the basis of symptoms and other factors. The test is not designed for population-based screening of asymptomatic people, he added.

Abbott announced plans to make up to 50 million tests available per month in the United States starting in October. The product comes with a free smartphone app that people can use to share results with an employer or with others as needed.
 

This article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved marketing of the first authorized diagnostic antigen test for SARS-CoV-2 that can be used without an analyzer.

Abbott

The BinaxNOW COVID-19 Ag Card (Abbott) is similar in some ways to a home pregnancy test. Clinicians read results on a card – one line for a negative result, two lines for positive.

A health care provider swabs a symptomatic patient’s nose, twirls the sample on a test card with a reagent, and waits approximately 15 minutes for results. No additional equipment is required.

Abbott expects the test to cost about $5.00, the company announced.

Office-based physicians, ED physicians, and school nurses could potentially use the product as a point-of-care test. The FDA granted the test emergency use authorization. It is approved for people suspected of having COVID-19 who are within 7 days of symptom onset.

“This new COVID-19 antigen test is an important addition to available tests because the results can be read in minutes, right off the testing card,” Jeff Shuren, MD, JD, director of the FDA’s Center for Devices and Radiological Health, wrote in a news release. “This means people will know if they have the virus in almost real time.”

“This fits into the testing landscape as a simple, inexpensive test that does not require additional equipment,” Marcus Lynch, PhD, assistant manager of the Health Care Horizon Scanning program at ECRI, told Medscape Medical News when asked to comment. ECRI is an independent, nonprofit organization that reviews and analyses COVID-19 therapeutics and diagnostics.

The test could help with early triage of patients who test positive, perhaps alerting physicians to the need to start COVID-19 therapy, added Lynch, who specializes in immunology and vaccine development. The test also could be useful in low-resource settings.

The FDA included a caveat: antigen tests are generally less sensitive than molecular assays. “Due to the potential for decreased sensitivity compared to molecular assays, negative results from an antigen test may need to be confirmed with a molecular test prior to making treatment decisions,” the agency noted.

Lynch agreed and said that when a patient tests negative, physicians still need to use their clinical judgment on the basis of symptoms and other factors. The test is not designed for population-based screening of asymptomatic people, he added.

Abbott announced plans to make up to 50 million tests available per month in the United States starting in October. The product comes with a free smartphone app that people can use to share results with an employer or with others as needed.
 

This article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved marketing of the first authorized diagnostic antigen test for SARS-CoV-2 that can be used without an analyzer.

Abbott

The BinaxNOW COVID-19 Ag Card (Abbott) is similar in some ways to a home pregnancy test. Clinicians read results on a card – one line for a negative result, two lines for positive.

A health care provider swabs a symptomatic patient’s nose, twirls the sample on a test card with a reagent, and waits approximately 15 minutes for results. No additional equipment is required.

Abbott expects the test to cost about $5.00, the company announced.

Office-based physicians, ED physicians, and school nurses could potentially use the product as a point-of-care test. The FDA granted the test emergency use authorization. It is approved for people suspected of having COVID-19 who are within 7 days of symptom onset.

“This new COVID-19 antigen test is an important addition to available tests because the results can be read in minutes, right off the testing card,” Jeff Shuren, MD, JD, director of the FDA’s Center for Devices and Radiological Health, wrote in a news release. “This means people will know if they have the virus in almost real time.”

“This fits into the testing landscape as a simple, inexpensive test that does not require additional equipment,” Marcus Lynch, PhD, assistant manager of the Health Care Horizon Scanning program at ECRI, told Medscape Medical News when asked to comment. ECRI is an independent, nonprofit organization that reviews and analyses COVID-19 therapeutics and diagnostics.

The test could help with early triage of patients who test positive, perhaps alerting physicians to the need to start COVID-19 therapy, added Lynch, who specializes in immunology and vaccine development. The test also could be useful in low-resource settings.

The FDA included a caveat: antigen tests are generally less sensitive than molecular assays. “Due to the potential for decreased sensitivity compared to molecular assays, negative results from an antigen test may need to be confirmed with a molecular test prior to making treatment decisions,” the agency noted.

Lynch agreed and said that when a patient tests negative, physicians still need to use their clinical judgment on the basis of symptoms and other factors. The test is not designed for population-based screening of asymptomatic people, he added.

Abbott announced plans to make up to 50 million tests available per month in the United States starting in October. The product comes with a free smartphone app that people can use to share results with an employer or with others as needed.
 

This article first appeared on Medscape.com.