Heart Failure

BARCELONA – The SGLT2 inhibitor dapagliflozin (Farxiga) became the third agent from the class to show evidence for efficacy in patients with heart failure with preserved ejection fraction (HFpEF) in results from more than 6,200 randomized patients in the DELIVER trial.

These results proved that dapagliflozin treatment benefits patients with heart failure regardless of their left ventricular function, when considered in tandem with previously reported findings in the DAPA-HF trial that tested the same drug in patients with heart failure with reduced ejection fraction (HFrEF). The DELIVER results for dapagliflozin also highlighted an apparent class effect for heart failure from agents from the sodium-glucose cotransporter 2 (SGLT2) inhibitor class, because of similar, prior findings for two other drugs in the class: empagliflozin (Jardiance) and sotagliflozin (approved in Europe and sold under the name Zynquista).

The upshot, said experts, is that the DELIVER results have further solidified a new paradigm for treating patients with heart failure that is much more agnostic when it comes to left ventricular function and underscores the need to quickly start SGLT2 inhibitor treatment in patients as soon as they receive a heart failure diagnosis, without the need to first measure and consider a patient’s left ventricular ejection fraction.

The new data support the use of SGLT2 inhibitors as “foundational agents for virtually all patients with heart failure” regardless of their ejection fraction or whether or not they have type 2 diabetes, said Scott D. Solomon, MD, who presented the primary results from the DELIVER trial at the annual congress of the European Society of Cardiology. Simultaneous publication of the findings occurred online in The New England Journal of Medicine.

MDedge News/Mitchel L. Zoler

Combined analyses document consistency

Combined analysis of the DELIVER results with the findings from DAPA-HF in a prespecified analysis that included a total of 11,007 patients with heart failure across the full spectrum of ejection fraction values (with individual patients having values as low as less than 20% or as high as more than 70%) showed a consistent benefit from dapagliflozin treatment for significantly reducing the combined endpoint of cardiovascular death or hospitalization for heart failure by about 22%, compared with placebo, across the complete range of this ejection fraction continuum.

The consistency of the benefit, regardless of left ventricular function, “is important clinically, as patients often have to wait for a heart scan to measure ejection fraction and decide on which therapies are indicated,” said Pardeep S. Jhund, MBChB, PhD, who reported this analysis in a separate talk at the congress and in a simultaneous publicationonline in Nature Medicine. Provided patients have no contraindications to treatment with dapagliflozin or another evidence-based SGLT2 inhibitor, prescribing this class prior to imaging to assess ejection fraction “speeds access to this life-saving medication,” said Dr. Jhund, a professor of cardiology and epidemiology at the University of Glasgow.

MDedge News/Mitchel L. Zoler

MDedge News/Mitchel L. Zoler

A ‘swan song’ for ejection fraction

“The striking consistency of effect across the entire ejection fraction range” from SGLT2 inhibitors heralds a “swan song for ejection fraction,” commented Frank Ruschitzka, MD, director of the Heart Center of the University Hospital of Zürich and designated discussant for Dr. Vaduganathan’s report. He also predicted that the medical societies that produce recommendations for managing patient with heart failure will soon, based on the accumulated data, give SGLT2 inhibitors a strong recommendation for use on most heart failure patients, sentiments echoed by several other discussants at the meeting and by editorialists who wrote about the newly published studies.

“SGLT2 inhibitors are the bedrock of therapy for heart failure regardless of ejection fraction or care setting,” wrote Katherine R. Tuttle, MD, and Janani Rangaswami, MD, in an editorial that accompanied the combined analysis published by Dr. Vaduganathan.

DELIVER was funded by AstraZeneca, the company that markets dapagliflozin. Dr. Solomon has been a consultant to and received research funding from AstraZeneca and numerous other companies. Dr. Jhund has received research funding from AstraZeneca. Dr. Vaduganathan has been an advisor to and received research funding from AstraZeneca and numerous other companies. Dr. Tuttle has been a consultant to AstraZeneca as well as Bayer, Boehringer Ingelheim, Eli Lilly, Gilead, Goldfinch Bio, Novo Nordisk, and Travere. Dr. Rangaswami has been a consultant to AstraZeneca as well as Boehringer Ingelheim, Edwards, and Eli Lilly, and she has been an advisor to Procyrion.

BARCELONA – The SGLT2 inhibitor dapagliflozin (Farxiga) became the third agent from the class to show evidence for efficacy in patients with heart failure with preserved ejection fraction (HFpEF) in results from more than 6,200 randomized patients in the DELIVER trial.

These results proved that dapagliflozin treatment benefits patients with heart failure regardless of their left ventricular function, when considered in tandem with previously reported findings in the DAPA-HF trial that tested the same drug in patients with heart failure with reduced ejection fraction (HFrEF). The DELIVER results for dapagliflozin also highlighted an apparent class effect for heart failure from agents from the sodium-glucose cotransporter 2 (SGLT2) inhibitor class, because of similar, prior findings for two other drugs in the class: empagliflozin (Jardiance) and sotagliflozin (approved in Europe and sold under the name Zynquista).

The upshot, said experts, is that the DELIVER results have further solidified a new paradigm for treating patients with heart failure that is much more agnostic when it comes to left ventricular function and underscores the need to quickly start SGLT2 inhibitor treatment in patients as soon as they receive a heart failure diagnosis, without the need to first measure and consider a patient’s left ventricular ejection fraction.

The new data support the use of SGLT2 inhibitors as “foundational agents for virtually all patients with heart failure” regardless of their ejection fraction or whether or not they have type 2 diabetes, said Scott D. Solomon, MD, who presented the primary results from the DELIVER trial at the annual congress of the European Society of Cardiology. Simultaneous publication of the findings occurred online in The New England Journal of Medicine.

MDedge News/Mitchel L. Zoler

Combined analyses document consistency

Combined analysis of the DELIVER results with the findings from DAPA-HF in a prespecified analysis that included a total of 11,007 patients with heart failure across the full spectrum of ejection fraction values (with individual patients having values as low as less than 20% or as high as more than 70%) showed a consistent benefit from dapagliflozin treatment for significantly reducing the combined endpoint of cardiovascular death or hospitalization for heart failure by about 22%, compared with placebo, across the complete range of this ejection fraction continuum.

The consistency of the benefit, regardless of left ventricular function, “is important clinically, as patients often have to wait for a heart scan to measure ejection fraction and decide on which therapies are indicated,” said Pardeep S. Jhund, MBChB, PhD, who reported this analysis in a separate talk at the congress and in a simultaneous publicationonline in Nature Medicine. Provided patients have no contraindications to treatment with dapagliflozin or another evidence-based SGLT2 inhibitor, prescribing this class prior to imaging to assess ejection fraction “speeds access to this life-saving medication,” said Dr. Jhund, a professor of cardiology and epidemiology at the University of Glasgow.

MDedge News/Mitchel L. Zoler

MDedge News/Mitchel L. Zoler

A ‘swan song’ for ejection fraction

“The striking consistency of effect across the entire ejection fraction range” from SGLT2 inhibitors heralds a “swan song for ejection fraction,” commented Frank Ruschitzka, MD, director of the Heart Center of the University Hospital of Zürich and designated discussant for Dr. Vaduganathan’s report. He also predicted that the medical societies that produce recommendations for managing patient with heart failure will soon, based on the accumulated data, give SGLT2 inhibitors a strong recommendation for use on most heart failure patients, sentiments echoed by several other discussants at the meeting and by editorialists who wrote about the newly published studies.

“SGLT2 inhibitors are the bedrock of therapy for heart failure regardless of ejection fraction or care setting,” wrote Katherine R. Tuttle, MD, and Janani Rangaswami, MD, in an editorial that accompanied the combined analysis published by Dr. Vaduganathan.

DELIVER was funded by AstraZeneca, the company that markets dapagliflozin. Dr. Solomon has been a consultant to and received research funding from AstraZeneca and numerous other companies. Dr. Jhund has received research funding from AstraZeneca. Dr. Vaduganathan has been an advisor to and received research funding from AstraZeneca and numerous other companies. Dr. Tuttle has been a consultant to AstraZeneca as well as Bayer, Boehringer Ingelheim, Eli Lilly, Gilead, Goldfinch Bio, Novo Nordisk, and Travere. Dr. Rangaswami has been a consultant to AstraZeneca as well as Boehringer Ingelheim, Edwards, and Eli Lilly, and she has been an advisor to Procyrion.

BARCELONA – The SGLT2 inhibitor dapagliflozin (Farxiga) became the third agent from the class to show evidence for efficacy in patients with heart failure with preserved ejection fraction (HFpEF) in results from more than 6,200 randomized patients in the DELIVER trial.

These results proved that dapagliflozin treatment benefits patients with heart failure regardless of their left ventricular function, when considered in tandem with previously reported findings in the DAPA-HF trial that tested the same drug in patients with heart failure with reduced ejection fraction (HFrEF). The DELIVER results for dapagliflozin also highlighted an apparent class effect for heart failure from agents from the sodium-glucose cotransporter 2 (SGLT2) inhibitor class, because of similar, prior findings for two other drugs in the class: empagliflozin (Jardiance) and sotagliflozin (approved in Europe and sold under the name Zynquista).

The upshot, said experts, is that the DELIVER results have further solidified a new paradigm for treating patients with heart failure that is much more agnostic when it comes to left ventricular function and underscores the need to quickly start SGLT2 inhibitor treatment in patients as soon as they receive a heart failure diagnosis, without the need to first measure and consider a patient’s left ventricular ejection fraction.

The new data support the use of SGLT2 inhibitors as “foundational agents for virtually all patients with heart failure” regardless of their ejection fraction or whether or not they have type 2 diabetes, said Scott D. Solomon, MD, who presented the primary results from the DELIVER trial at the annual congress of the European Society of Cardiology. Simultaneous publication of the findings occurred online in The New England Journal of Medicine.

MDedge News/Mitchel L. Zoler

Combined analyses document consistency

Combined analysis of the DELIVER results with the findings from DAPA-HF in a prespecified analysis that included a total of 11,007 patients with heart failure across the full spectrum of ejection fraction values (with individual patients having values as low as less than 20% or as high as more than 70%) showed a consistent benefit from dapagliflozin treatment for significantly reducing the combined endpoint of cardiovascular death or hospitalization for heart failure by about 22%, compared with placebo, across the complete range of this ejection fraction continuum.

The consistency of the benefit, regardless of left ventricular function, “is important clinically, as patients often have to wait for a heart scan to measure ejection fraction and decide on which therapies are indicated,” said Pardeep S. Jhund, MBChB, PhD, who reported this analysis in a separate talk at the congress and in a simultaneous publicationonline in Nature Medicine. Provided patients have no contraindications to treatment with dapagliflozin or another evidence-based SGLT2 inhibitor, prescribing this class prior to imaging to assess ejection fraction “speeds access to this life-saving medication,” said Dr. Jhund, a professor of cardiology and epidemiology at the University of Glasgow.

MDedge News/Mitchel L. Zoler

MDedge News/Mitchel L. Zoler

A ‘swan song’ for ejection fraction

“The striking consistency of effect across the entire ejection fraction range” from SGLT2 inhibitors heralds a “swan song for ejection fraction,” commented Frank Ruschitzka, MD, director of the Heart Center of the University Hospital of Zürich and designated discussant for Dr. Vaduganathan’s report. He also predicted that the medical societies that produce recommendations for managing patient with heart failure will soon, based on the accumulated data, give SGLT2 inhibitors a strong recommendation for use on most heart failure patients, sentiments echoed by several other discussants at the meeting and by editorialists who wrote about the newly published studies.

“SGLT2 inhibitors are the bedrock of therapy for heart failure regardless of ejection fraction or care setting,” wrote Katherine R. Tuttle, MD, and Janani Rangaswami, MD, in an editorial that accompanied the combined analysis published by Dr. Vaduganathan.

DELIVER was funded by AstraZeneca, the company that markets dapagliflozin. Dr. Solomon has been a consultant to and received research funding from AstraZeneca and numerous other companies. Dr. Jhund has received research funding from AstraZeneca. Dr. Vaduganathan has been an advisor to and received research funding from AstraZeneca and numerous other companies. Dr. Tuttle has been a consultant to AstraZeneca as well as Bayer, Boehringer Ingelheim, Eli Lilly, Gilead, Goldfinch Bio, Novo Nordisk, and Travere. Dr. Rangaswami has been a consultant to AstraZeneca as well as Boehringer Ingelheim, Edwards, and Eli Lilly, and she has been an advisor to Procyrion.

Patients who received a first prescription for medicinal cannabis for chronic pain were more likely to have new onset of arrhythmia – bradyarrhythmia, tachyarrhythmia, or a conduction disorder – within 6 months than were similar nonusers, in a new case-control study.

VladK213/Getty Images

There were no between-group differences in the incidence of heart failure or acute coronary syndrome.

The researchers identified 5,071 patients in a national Danish registry who had filled at least one prescription for medicinal cannabis for chronic pain and matched each patient with five patients of the same sex, age range, and type of chronic pain who did not receive this therapy.

The relative risk for arrhythmia was 83% higher in those who used medicinal cannabis than it was in the other patients, study author Nina Nouhravesh, MD, told this news organization in an email.

However, the absolute risks for arrhythmia were slight – a 0.86% risk (95% confidence interval, 0.61%-1.1%) in medicinal cannabis users versus a 0.47% risk (95% CI, 0.38%-0.56%) in those who did not use medicinal cannabis.

“Since medical cannabis is a relatively new drug for a large market of patients with chronic pain, it is important to investigate and report serious side effects,” said Dr. Nouhravesh, from Gentofte University Hospital, Denmark.

The study results, she said, suggest that “there may be a previously unreported risk of arrhythmias following medical cannabis use.”

“Even though the absolute risk difference is small, both patients and physicians should have as much information as possible when weighing up the pros and cons of any treatment,” Dr. Nouhravesh said, adding that “the findings of this study raise concerns for both legal and illegal [cannabis] use worldwide.”

The results will be presented at the annual European Society of Cardiology (ESC) Congress 2022.
 

Too soon to tell?

However, Brian Olshansky, MD, who was not involved with this research, cautions that it is important to consider several study limitations before drawing clinical implications.

“Other data and reports have considered the possibility of arrhythmias in relationship to marijuana use, and the data go in both directions,” Dr. Olshansky, a clinical cardiac electrophysiologist and professor emeritus at University of Iowa Hospitals, Iowa City, pointed out in an email.

“Importantly, arrhythmias, by themselves, are not necessarily consequential,” he stressed. “In any case,” he added, the risks in the current study are “extraordinarily small.”

Sinus bradycardia, sinus tachycardia, and premature atrial or ventricular contractions could be totally benign, he said. On the other hand, arrhythmias may indicate the presence of atrial fibrillation, atrial flutter, ventricular tachycardia, and ventricular fibrillation, which are potentially dangerous.

There may be a specific “high risk” group who can develop potentially serious arrhythmias, Dr. Olshansky suggested.

“There is no evidence that any of these patients underwent or required any treatment for their arrhythmia or that stopping or starting the cannabinoids affected the arrhythmia one way or the other,” he said. “In addition, there is no dose/arrhythmia relationship.”

More patients in the medicinal cannabis group than in the nonuser group were also taking opioids (49% vs. 30%), nonsteroidal anti-inflammatory drugs (24% vs. 19%), antiepileptics (35% vs. 23%), or tricyclic antidepressants (11% vs. 4%), he noted.

In summary, according to Dr. Olshansky, “these data pose no obvious health concern and provide no vital knowledge for physicians prescribing cannabis.”

“My concern is that the information will be overblown,” he cautioned. “If the cannabinoid actually has benefit in terms of pain reduction, its use may be mitigated based on the fear of an arrhythmia that may occur – but the risk of an arrhythmia, in any event, is very small and undefined in terms of its seriousness.”
 

Cancer, musculoskeletal, and neurologic pain

For this analysis, the researchers identified 1.8 million patients in Denmark who were diagnosed with chronic pain between 2018 and 2021.

Of those, around 5,000 patients had claimed at least one prescription of medicinal cannabis (dronabinol 29%, cannabinoids 46%, or cannabidiol 25%).

The patients had a median age of 60 years, and 63% were women.

The cannabis users had been prescribed this therapy for musculoskeletal (35%), cancer (18%), neurological (14%), or other (33%) pain, Dr. Nouhravesh said. 

The researchers and Dr. Olshansky have no relevant financial disclosures.  

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

Patients who received a first prescription for medicinal cannabis for chronic pain were more likely to have new onset of arrhythmia – bradyarrhythmia, tachyarrhythmia, or a conduction disorder – within 6 months than were similar nonusers, in a new case-control study.

VladK213/Getty Images

There were no between-group differences in the incidence of heart failure or acute coronary syndrome.

The researchers identified 5,071 patients in a national Danish registry who had filled at least one prescription for medicinal cannabis for chronic pain and matched each patient with five patients of the same sex, age range, and type of chronic pain who did not receive this therapy.

The relative risk for arrhythmia was 83% higher in those who used medicinal cannabis than it was in the other patients, study author Nina Nouhravesh, MD, told this news organization in an email.

However, the absolute risks for arrhythmia were slight – a 0.86% risk (95% confidence interval, 0.61%-1.1%) in medicinal cannabis users versus a 0.47% risk (95% CI, 0.38%-0.56%) in those who did not use medicinal cannabis.

“Since medical cannabis is a relatively new drug for a large market of patients with chronic pain, it is important to investigate and report serious side effects,” said Dr. Nouhravesh, from Gentofte University Hospital, Denmark.

The study results, she said, suggest that “there may be a previously unreported risk of arrhythmias following medical cannabis use.”

“Even though the absolute risk difference is small, both patients and physicians should have as much information as possible when weighing up the pros and cons of any treatment,” Dr. Nouhravesh said, adding that “the findings of this study raise concerns for both legal and illegal [cannabis] use worldwide.”

The results will be presented at the annual European Society of Cardiology (ESC) Congress 2022.
 

Too soon to tell?

However, Brian Olshansky, MD, who was not involved with this research, cautions that it is important to consider several study limitations before drawing clinical implications.

“Other data and reports have considered the possibility of arrhythmias in relationship to marijuana use, and the data go in both directions,” Dr. Olshansky, a clinical cardiac electrophysiologist and professor emeritus at University of Iowa Hospitals, Iowa City, pointed out in an email.

“Importantly, arrhythmias, by themselves, are not necessarily consequential,” he stressed. “In any case,” he added, the risks in the current study are “extraordinarily small.”

Sinus bradycardia, sinus tachycardia, and premature atrial or ventricular contractions could be totally benign, he said. On the other hand, arrhythmias may indicate the presence of atrial fibrillation, atrial flutter, ventricular tachycardia, and ventricular fibrillation, which are potentially dangerous.

There may be a specific “high risk” group who can develop potentially serious arrhythmias, Dr. Olshansky suggested.

“There is no evidence that any of these patients underwent or required any treatment for their arrhythmia or that stopping or starting the cannabinoids affected the arrhythmia one way or the other,” he said. “In addition, there is no dose/arrhythmia relationship.”

More patients in the medicinal cannabis group than in the nonuser group were also taking opioids (49% vs. 30%), nonsteroidal anti-inflammatory drugs (24% vs. 19%), antiepileptics (35% vs. 23%), or tricyclic antidepressants (11% vs. 4%), he noted.

In summary, according to Dr. Olshansky, “these data pose no obvious health concern and provide no vital knowledge for physicians prescribing cannabis.”

“My concern is that the information will be overblown,” he cautioned. “If the cannabinoid actually has benefit in terms of pain reduction, its use may be mitigated based on the fear of an arrhythmia that may occur – but the risk of an arrhythmia, in any event, is very small and undefined in terms of its seriousness.”
 

Cancer, musculoskeletal, and neurologic pain

For this analysis, the researchers identified 1.8 million patients in Denmark who were diagnosed with chronic pain between 2018 and 2021.

Of those, around 5,000 patients had claimed at least one prescription of medicinal cannabis (dronabinol 29%, cannabinoids 46%, or cannabidiol 25%).

The patients had a median age of 60 years, and 63% were women.

The cannabis users had been prescribed this therapy for musculoskeletal (35%), cancer (18%), neurological (14%), or other (33%) pain, Dr. Nouhravesh said. 

The researchers and Dr. Olshansky have no relevant financial disclosures.  

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

Patients who received a first prescription for medicinal cannabis for chronic pain were more likely to have new onset of arrhythmia – bradyarrhythmia, tachyarrhythmia, or a conduction disorder – within 6 months than were similar nonusers, in a new case-control study.

VladK213/Getty Images

There were no between-group differences in the incidence of heart failure or acute coronary syndrome.

The researchers identified 5,071 patients in a national Danish registry who had filled at least one prescription for medicinal cannabis for chronic pain and matched each patient with five patients of the same sex, age range, and type of chronic pain who did not receive this therapy.

The relative risk for arrhythmia was 83% higher in those who used medicinal cannabis than it was in the other patients, study author Nina Nouhravesh, MD, told this news organization in an email.

However, the absolute risks for arrhythmia were slight – a 0.86% risk (95% confidence interval, 0.61%-1.1%) in medicinal cannabis users versus a 0.47% risk (95% CI, 0.38%-0.56%) in those who did not use medicinal cannabis.

“Since medical cannabis is a relatively new drug for a large market of patients with chronic pain, it is important to investigate and report serious side effects,” said Dr. Nouhravesh, from Gentofte University Hospital, Denmark.

The study results, she said, suggest that “there may be a previously unreported risk of arrhythmias following medical cannabis use.”

“Even though the absolute risk difference is small, both patients and physicians should have as much information as possible when weighing up the pros and cons of any treatment,” Dr. Nouhravesh said, adding that “the findings of this study raise concerns for both legal and illegal [cannabis] use worldwide.”

The results will be presented at the annual European Society of Cardiology (ESC) Congress 2022.
 

Too soon to tell?

However, Brian Olshansky, MD, who was not involved with this research, cautions that it is important to consider several study limitations before drawing clinical implications.

“Other data and reports have considered the possibility of arrhythmias in relationship to marijuana use, and the data go in both directions,” Dr. Olshansky, a clinical cardiac electrophysiologist and professor emeritus at University of Iowa Hospitals, Iowa City, pointed out in an email.

“Importantly, arrhythmias, by themselves, are not necessarily consequential,” he stressed. “In any case,” he added, the risks in the current study are “extraordinarily small.”

Sinus bradycardia, sinus tachycardia, and premature atrial or ventricular contractions could be totally benign, he said. On the other hand, arrhythmias may indicate the presence of atrial fibrillation, atrial flutter, ventricular tachycardia, and ventricular fibrillation, which are potentially dangerous.

There may be a specific “high risk” group who can develop potentially serious arrhythmias, Dr. Olshansky suggested.

“There is no evidence that any of these patients underwent or required any treatment for their arrhythmia or that stopping or starting the cannabinoids affected the arrhythmia one way or the other,” he said. “In addition, there is no dose/arrhythmia relationship.”

More patients in the medicinal cannabis group than in the nonuser group were also taking opioids (49% vs. 30%), nonsteroidal anti-inflammatory drugs (24% vs. 19%), antiepileptics (35% vs. 23%), or tricyclic antidepressants (11% vs. 4%), he noted.

In summary, according to Dr. Olshansky, “these data pose no obvious health concern and provide no vital knowledge for physicians prescribing cannabis.”

“My concern is that the information will be overblown,” he cautioned. “If the cannabinoid actually has benefit in terms of pain reduction, its use may be mitigated based on the fear of an arrhythmia that may occur – but the risk of an arrhythmia, in any event, is very small and undefined in terms of its seriousness.”
 

Cancer, musculoskeletal, and neurologic pain

For this analysis, the researchers identified 1.8 million patients in Denmark who were diagnosed with chronic pain between 2018 and 2021.

Of those, around 5,000 patients had claimed at least one prescription of medicinal cannabis (dronabinol 29%, cannabinoids 46%, or cannabidiol 25%).

The patients had a median age of 60 years, and 63% were women.

The cannabis users had been prescribed this therapy for musculoskeletal (35%), cancer (18%), neurological (14%), or other (33%) pain, Dr. Nouhravesh said. 

The researchers and Dr. Olshansky have no relevant financial disclosures.  

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

BARCELONA – Patients with hypertension who took their antihypertensive medication in the evening or in the morning had similar rates of cardiovascular events over the following 5 years, in the much-anticipated TIME trial.

The trial, which contradicts several previous studies suggesting that evening dosing may be better, was presented at the annual congress of the European Society of Cardiology. 

MDedge News/Mitchel L. Zoler

“The key message from this study is that taking antihypertensive medication in the evening makes no difference at all from taking it in the morning for the prevention of heart attacks, strokes, and vascular deaths,” concluded TIME lead investigator Tom MacDonald, MBChB, MD, professor of clinical pharmacology & pharmacoepidemiology at the University of Dundee (Scotland).

The hazard ratio was 0.95 for the primary endpoint, a composite of hospitalization for nonfatal myocardial infarction, nonfatal stroke, or vascular death, in the intention-to-treat population.

Similar results, with a hazard ratio around 1, were seen for all the secondary outcomes and in all subgroups.

“There is nothing to see – not a smidge of a difference – in the primary outcome or any of the secondary outcomes,” Dr. MacDonald commented.

The study also showed that evening dosing was not harmful in terms of falls or other adverse effects. Dr. MacDonald explained that taking the medication at night could result in an increase in nocturnal hypotension that may translate into more dizziness and falls if patients get up to use the bathroom during the night. “But, if anything, there were more dizzy turns during the day. The rate of fractures and hospitalization for fractures were identical in the two groups,” he reported.

“Our take-home message is that patients can take their blood pressure tablets at any time they like – whenever is most convenient – as long as they take them. It’s probably best to get into a routine of taking your tablets at the same time every day. That way you are more likely to remember to take them – but it won’t matter if that is in the morning or in the evening,” he said. 

Non-dippers

Dr. MacDonald explained that the rationale for the study was that in some patients blood pressure does not drop at night, a group known as “non-dippers,” and nighttime blood pressure is the best predictor of bad outcomes. In addition, previous studies have suggested that evening dosing of antihypertensives reduces nighttime blood pressure more effectively than daytime dosing.

“We and others thought that giving medication in the evening so that its peak effect occurs during the night might be beneficial,” he said. “We did the trial because if it had turned out that taking tablets in the evening was beneficial, it would have been one of the cheapest and most cost-effective interventions known to man. It is a nice hypothesis and most people thought this would turn out with a benefit, but it actually didn’t.”

The study did find some differences in the blood pressure profile between the two dosing schedules.

“Our results show that when antihypertensive medication is taken in the morning, then blood pressure is higher in the morning and lower in the evening. With evening dosing, blood pressure is lower in the morning and higher in the evening. It’s not a huge difference – just 1-2 mm Hg – and this didn’t translate into any difference in outcomes,” Dr. MacDonald said. 

“Ideally we need medication that lowers blood pressure effectively over the whole 24-hour period. That is where the push should be,” he added.

The TIME study randomized 21,104 patients with treated hypertension to take their antihypertensive medication in the morning or in the evening. Baseline characteristics show the average age of participants was 65 years, 14% had diabetes, 4% were smokers, 13% had prior cardiovascular disease, and mean blood pressure at entry was 135/79 mmHg.

TIME was a pragmatic study, with participants recruited from primary and secondary care registering on the Internet, and information on hospitalizations and deaths obtained from participants by email and through record linkage to national databases, with further data gathered from family doctors and hospitals and independently adjudicated by a blinded committee.

The median follow-up duration was 5.2 years, but some patients were followed for over 9 years.

The primary endpoint occurred in 362 (3.4%) participants in the evening-dosing group (0.69 events per 100 patient-years) and 390 (3.7%) in the morning-dosing group (0.72 events per 100 patient-years), giving an unadjusted hazard ratio of 0.95 (95% confidence interval, 0.83-1.10; P = .53).

What to recommend in clinical practice?

Outside commentators had mixed opinions on how the TIME results should be applied to clinical practice.

Discussant of the TIME study at the ESC Hotline session, Rhian Touyz, MBBCh, University of Glasgow (Scotland), said the trial asked a “very pertinent” question and the data “are certainly provocative.”

She cited several previous studies suggesting that evening dosing improved nighttime blood pressure and reduced cardiovascular events.

“The finding of no difference in event rate in the TIME study is therefore very intriguing.”

She pointed out that other studies have shown benefit of nighttime dosing in certain patient groups such as those with sleep apnea, non-dippers, and those with nocturnal hypertension.  

“With all these previous data, we have to ask why the TIME trial has produced this unexpected result,” she said.

Dr. MacDonald replied that the study was completely neutral. “That is the result, and I believe it is definitive. I’m absolutely confident that we did the study as best we could. All events were adjudicated. Compliance was quite good at 60%. I can’t believe there is anything in our data that invalidates these results,” he said. “If we want to look at specific groups of patients then we have to do larger studies in those particular groups, but for a general population of hypertensive patients we didn’t find any difference at all in morning versus evening dosing.”

The TIME results are in direct contradiction of a previous high-profile study – the Hygia Chronotherapy Trial – published in 2020, which found a large protective effect of nocturnal dosing on cardiovascular events, and attracted much media attention. But this study has subsequently attracted criticism, with an “expression of concern” and a commentary raising several questions. 

And a systematic review from the International Society of Hypertension published earlier this month concludes that previous trials of bedtime antihypertensive dosing had “major flaws.”

The review notes that three ongoing, well-designed, prospective, randomized controlled outcome trials are expected to provide high-quality data on the efficacy and safety of evening or bedtime versus morning drug dosing.

“Until that information is available, preferred use of bedtime drug dosing of antihypertensive drugs should not be routinely recommended in clinical practice. Complete 24-h control of BP should be targeted using readily available, long-acting antihypertensive medications as monotherapy or combinations administered in a single morning dose,” it concludes.

On the new TIME results, lead author of the ISH review, George Stergiou, MD, commented: “The benefits of bedtime dosing were not confirmed – as we well expected. So, I think bedtime drug dosing should not be routinely recommended in clinical practice.”

Although the TIME trial did not show any harms with bedtime dose, Dr. Stergiou added, “I am not too happy with their conclusion that patients should do as they wish. The vast majority of well-conducted outcomes studies which we use to guide the treatment of hypertension administered all drugs in the morning.”

One of the authors of the commentary criticizing the Hygia trial, Sverre E. Kjeldsen, MD, University of Oslo, said in an interview that the TIME trial was an important study, far more reliable than the Hygia study, and the results were as expected.

“From a scientific point of view, patients have a choice as to when to take their medication, but we strongly recommend taking blood pressure meds in the morning. Adherence is proven to be worse at bedtime. However, physicians may still consider bedtime dosing in patients proven to have high night-time blood pressure,” Dr. Kjeldsen added.

Lead investigator of the Hygia study, Ramón C. Hermida, PhD, University of Vigo (Spain), told this news organization he and his coauthors are standing by their results.

“The design and conduct of the TIME trial does not comply with the quality requirements listed in the guidelines by the International Society for Chronobiology for conducting chronotherapy trials in hypertension, and the results are not in line with the reported findings of multiple clinical trials on the effects of timed hypertension treatment on blood pressure control and circadian pattern regulation, kidney function, and cardiac pathology,” Dr. Hermida said.

Chair of an ESC press conference on the TIME study, Steen Dalby Kristensen, MD, Aarhus University Hospital, Skejby, Denmark, said he thought the trial was “very well done.”

The TIME results, he said, “are quite clear, whether you take your blood pressure tablets in the morning or the evening it makes no difference for the hard outcomes that we fear in patients with hypertension.  

“I think that this solves a question that we’ve had for a long time now,” he commented. “Even though there were some changes in the blood pressure measured in the evening or in the morning it doesn’t seem to matter in terms of clinical events. This means that life might be a bit easier for patients in that they can choose when they take their medication at the time most convenient to them.  

“I don’t know why previous studies suggested such a big benefit of evening dosing,” he added. “I would say the TIME trial is a more definitive result. It is a very important trial.”

Dipti Itchhaporia, MD, University of California, Irvine, and immediate past president of the American College of Cardiology, agreed that the TIME study was well conducted.

“On the basis of these results I wouldn’t recommend a specific time,” she said. “That’s kind of a relief, as it can be difficult to always take medications at a set time and this gives patients more flexibility.”

She suggested a possible alternative approach for patients taking more than one drug – taking one in the morning and the other in the evening. “That might give better 24-hour coverage.”

The study was funded by the British Heart Foundation. Dr. MacDonald has reported receiving research funding from Novartis and consulting fees from Novartis and AstraZeneca.

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

BARCELONA – Patients with hypertension who took their antihypertensive medication in the evening or in the morning had similar rates of cardiovascular events over the following 5 years, in the much-anticipated TIME trial.

The trial, which contradicts several previous studies suggesting that evening dosing may be better, was presented at the annual congress of the European Society of Cardiology. 

MDedge News/Mitchel L. Zoler

“The key message from this study is that taking antihypertensive medication in the evening makes no difference at all from taking it in the morning for the prevention of heart attacks, strokes, and vascular deaths,” concluded TIME lead investigator Tom MacDonald, MBChB, MD, professor of clinical pharmacology & pharmacoepidemiology at the University of Dundee (Scotland).

The hazard ratio was 0.95 for the primary endpoint, a composite of hospitalization for nonfatal myocardial infarction, nonfatal stroke, or vascular death, in the intention-to-treat population.

Similar results, with a hazard ratio around 1, were seen for all the secondary outcomes and in all subgroups.

“There is nothing to see – not a smidge of a difference – in the primary outcome or any of the secondary outcomes,” Dr. MacDonald commented.

The study also showed that evening dosing was not harmful in terms of falls or other adverse effects. Dr. MacDonald explained that taking the medication at night could result in an increase in nocturnal hypotension that may translate into more dizziness and falls if patients get up to use the bathroom during the night. “But, if anything, there were more dizzy turns during the day. The rate of fractures and hospitalization for fractures were identical in the two groups,” he reported.

“Our take-home message is that patients can take their blood pressure tablets at any time they like – whenever is most convenient – as long as they take them. It’s probably best to get into a routine of taking your tablets at the same time every day. That way you are more likely to remember to take them – but it won’t matter if that is in the morning or in the evening,” he said. 

Non-dippers

Dr. MacDonald explained that the rationale for the study was that in some patients blood pressure does not drop at night, a group known as “non-dippers,” and nighttime blood pressure is the best predictor of bad outcomes. In addition, previous studies have suggested that evening dosing of antihypertensives reduces nighttime blood pressure more effectively than daytime dosing.

“We and others thought that giving medication in the evening so that its peak effect occurs during the night might be beneficial,” he said. “We did the trial because if it had turned out that taking tablets in the evening was beneficial, it would have been one of the cheapest and most cost-effective interventions known to man. It is a nice hypothesis and most people thought this would turn out with a benefit, but it actually didn’t.”

The study did find some differences in the blood pressure profile between the two dosing schedules.

“Our results show that when antihypertensive medication is taken in the morning, then blood pressure is higher in the morning and lower in the evening. With evening dosing, blood pressure is lower in the morning and higher in the evening. It’s not a huge difference – just 1-2 mm Hg – and this didn’t translate into any difference in outcomes,” Dr. MacDonald said. 

“Ideally we need medication that lowers blood pressure effectively over the whole 24-hour period. That is where the push should be,” he added.

The TIME study randomized 21,104 patients with treated hypertension to take their antihypertensive medication in the morning or in the evening. Baseline characteristics show the average age of participants was 65 years, 14% had diabetes, 4% were smokers, 13% had prior cardiovascular disease, and mean blood pressure at entry was 135/79 mmHg.

TIME was a pragmatic study, with participants recruited from primary and secondary care registering on the Internet, and information on hospitalizations and deaths obtained from participants by email and through record linkage to national databases, with further data gathered from family doctors and hospitals and independently adjudicated by a blinded committee.

The median follow-up duration was 5.2 years, but some patients were followed for over 9 years.

The primary endpoint occurred in 362 (3.4%) participants in the evening-dosing group (0.69 events per 100 patient-years) and 390 (3.7%) in the morning-dosing group (0.72 events per 100 patient-years), giving an unadjusted hazard ratio of 0.95 (95% confidence interval, 0.83-1.10; P = .53).

What to recommend in clinical practice?

Outside commentators had mixed opinions on how the TIME results should be applied to clinical practice.

Discussant of the TIME study at the ESC Hotline session, Rhian Touyz, MBBCh, University of Glasgow (Scotland), said the trial asked a “very pertinent” question and the data “are certainly provocative.”

She cited several previous studies suggesting that evening dosing improved nighttime blood pressure and reduced cardiovascular events.

“The finding of no difference in event rate in the TIME study is therefore very intriguing.”

She pointed out that other studies have shown benefit of nighttime dosing in certain patient groups such as those with sleep apnea, non-dippers, and those with nocturnal hypertension.  

“With all these previous data, we have to ask why the TIME trial has produced this unexpected result,” she said.

Dr. MacDonald replied that the study was completely neutral. “That is the result, and I believe it is definitive. I’m absolutely confident that we did the study as best we could. All events were adjudicated. Compliance was quite good at 60%. I can’t believe there is anything in our data that invalidates these results,” he said. “If we want to look at specific groups of patients then we have to do larger studies in those particular groups, but for a general population of hypertensive patients we didn’t find any difference at all in morning versus evening dosing.”

The TIME results are in direct contradiction of a previous high-profile study – the Hygia Chronotherapy Trial – published in 2020, which found a large protective effect of nocturnal dosing on cardiovascular events, and attracted much media attention. But this study has subsequently attracted criticism, with an “expression of concern” and a commentary raising several questions. 

And a systematic review from the International Society of Hypertension published earlier this month concludes that previous trials of bedtime antihypertensive dosing had “major flaws.”

The review notes that three ongoing, well-designed, prospective, randomized controlled outcome trials are expected to provide high-quality data on the efficacy and safety of evening or bedtime versus morning drug dosing.

“Until that information is available, preferred use of bedtime drug dosing of antihypertensive drugs should not be routinely recommended in clinical practice. Complete 24-h control of BP should be targeted using readily available, long-acting antihypertensive medications as monotherapy or combinations administered in a single morning dose,” it concludes.

On the new TIME results, lead author of the ISH review, George Stergiou, MD, commented: “The benefits of bedtime dosing were not confirmed – as we well expected. So, I think bedtime drug dosing should not be routinely recommended in clinical practice.”

Although the TIME trial did not show any harms with bedtime dose, Dr. Stergiou added, “I am not too happy with their conclusion that patients should do as they wish. The vast majority of well-conducted outcomes studies which we use to guide the treatment of hypertension administered all drugs in the morning.”

One of the authors of the commentary criticizing the Hygia trial, Sverre E. Kjeldsen, MD, University of Oslo, said in an interview that the TIME trial was an important study, far more reliable than the Hygia study, and the results were as expected.

“From a scientific point of view, patients have a choice as to when to take their medication, but we strongly recommend taking blood pressure meds in the morning. Adherence is proven to be worse at bedtime. However, physicians may still consider bedtime dosing in patients proven to have high night-time blood pressure,” Dr. Kjeldsen added.

Lead investigator of the Hygia study, Ramón C. Hermida, PhD, University of Vigo (Spain), told this news organization he and his coauthors are standing by their results.

“The design and conduct of the TIME trial does not comply with the quality requirements listed in the guidelines by the International Society for Chronobiology for conducting chronotherapy trials in hypertension, and the results are not in line with the reported findings of multiple clinical trials on the effects of timed hypertension treatment on blood pressure control and circadian pattern regulation, kidney function, and cardiac pathology,” Dr. Hermida said.

Chair of an ESC press conference on the TIME study, Steen Dalby Kristensen, MD, Aarhus University Hospital, Skejby, Denmark, said he thought the trial was “very well done.”

The TIME results, he said, “are quite clear, whether you take your blood pressure tablets in the morning or the evening it makes no difference for the hard outcomes that we fear in patients with hypertension.  

“I think that this solves a question that we’ve had for a long time now,” he commented. “Even though there were some changes in the blood pressure measured in the evening or in the morning it doesn’t seem to matter in terms of clinical events. This means that life might be a bit easier for patients in that they can choose when they take their medication at the time most convenient to them.  

“I don’t know why previous studies suggested such a big benefit of evening dosing,” he added. “I would say the TIME trial is a more definitive result. It is a very important trial.”

Dipti Itchhaporia, MD, University of California, Irvine, and immediate past president of the American College of Cardiology, agreed that the TIME study was well conducted.

“On the basis of these results I wouldn’t recommend a specific time,” she said. “That’s kind of a relief, as it can be difficult to always take medications at a set time and this gives patients more flexibility.”

She suggested a possible alternative approach for patients taking more than one drug – taking one in the morning and the other in the evening. “That might give better 24-hour coverage.”

The study was funded by the British Heart Foundation. Dr. MacDonald has reported receiving research funding from Novartis and consulting fees from Novartis and AstraZeneca.

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

BARCELONA – Patients with hypertension who took their antihypertensive medication in the evening or in the morning had similar rates of cardiovascular events over the following 5 years, in the much-anticipated TIME trial.

The trial, which contradicts several previous studies suggesting that evening dosing may be better, was presented at the annual congress of the European Society of Cardiology. 

MDedge News/Mitchel L. Zoler

“The key message from this study is that taking antihypertensive medication in the evening makes no difference at all from taking it in the morning for the prevention of heart attacks, strokes, and vascular deaths,” concluded TIME lead investigator Tom MacDonald, MBChB, MD, professor of clinical pharmacology & pharmacoepidemiology at the University of Dundee (Scotland).

The hazard ratio was 0.95 for the primary endpoint, a composite of hospitalization for nonfatal myocardial infarction, nonfatal stroke, or vascular death, in the intention-to-treat population.

Similar results, with a hazard ratio around 1, were seen for all the secondary outcomes and in all subgroups.

“There is nothing to see – not a smidge of a difference – in the primary outcome or any of the secondary outcomes,” Dr. MacDonald commented.

The study also showed that evening dosing was not harmful in terms of falls or other adverse effects. Dr. MacDonald explained that taking the medication at night could result in an increase in nocturnal hypotension that may translate into more dizziness and falls if patients get up to use the bathroom during the night. “But, if anything, there were more dizzy turns during the day. The rate of fractures and hospitalization for fractures were identical in the two groups,” he reported.

“Our take-home message is that patients can take their blood pressure tablets at any time they like – whenever is most convenient – as long as they take them. It’s probably best to get into a routine of taking your tablets at the same time every day. That way you are more likely to remember to take them – but it won’t matter if that is in the morning or in the evening,” he said. 

Non-dippers

Dr. MacDonald explained that the rationale for the study was that in some patients blood pressure does not drop at night, a group known as “non-dippers,” and nighttime blood pressure is the best predictor of bad outcomes. In addition, previous studies have suggested that evening dosing of antihypertensives reduces nighttime blood pressure more effectively than daytime dosing.

“We and others thought that giving medication in the evening so that its peak effect occurs during the night might be beneficial,” he said. “We did the trial because if it had turned out that taking tablets in the evening was beneficial, it would have been one of the cheapest and most cost-effective interventions known to man. It is a nice hypothesis and most people thought this would turn out with a benefit, but it actually didn’t.”

The study did find some differences in the blood pressure profile between the two dosing schedules.

“Our results show that when antihypertensive medication is taken in the morning, then blood pressure is higher in the morning and lower in the evening. With evening dosing, blood pressure is lower in the morning and higher in the evening. It’s not a huge difference – just 1-2 mm Hg – and this didn’t translate into any difference in outcomes,” Dr. MacDonald said. 

“Ideally we need medication that lowers blood pressure effectively over the whole 24-hour period. That is where the push should be,” he added.

The TIME study randomized 21,104 patients with treated hypertension to take their antihypertensive medication in the morning or in the evening. Baseline characteristics show the average age of participants was 65 years, 14% had diabetes, 4% were smokers, 13% had prior cardiovascular disease, and mean blood pressure at entry was 135/79 mmHg.

TIME was a pragmatic study, with participants recruited from primary and secondary care registering on the Internet, and information on hospitalizations and deaths obtained from participants by email and through record linkage to national databases, with further data gathered from family doctors and hospitals and independently adjudicated by a blinded committee.

The median follow-up duration was 5.2 years, but some patients were followed for over 9 years.

The primary endpoint occurred in 362 (3.4%) participants in the evening-dosing group (0.69 events per 100 patient-years) and 390 (3.7%) in the morning-dosing group (0.72 events per 100 patient-years), giving an unadjusted hazard ratio of 0.95 (95% confidence interval, 0.83-1.10; P = .53).

What to recommend in clinical practice?

Outside commentators had mixed opinions on how the TIME results should be applied to clinical practice.

Discussant of the TIME study at the ESC Hotline session, Rhian Touyz, MBBCh, University of Glasgow (Scotland), said the trial asked a “very pertinent” question and the data “are certainly provocative.”

She cited several previous studies suggesting that evening dosing improved nighttime blood pressure and reduced cardiovascular events.

“The finding of no difference in event rate in the TIME study is therefore very intriguing.”

She pointed out that other studies have shown benefit of nighttime dosing in certain patient groups such as those with sleep apnea, non-dippers, and those with nocturnal hypertension.  

“With all these previous data, we have to ask why the TIME trial has produced this unexpected result,” she said.

Dr. MacDonald replied that the study was completely neutral. “That is the result, and I believe it is definitive. I’m absolutely confident that we did the study as best we could. All events were adjudicated. Compliance was quite good at 60%. I can’t believe there is anything in our data that invalidates these results,” he said. “If we want to look at specific groups of patients then we have to do larger studies in those particular groups, but for a general population of hypertensive patients we didn’t find any difference at all in morning versus evening dosing.”

The TIME results are in direct contradiction of a previous high-profile study – the Hygia Chronotherapy Trial – published in 2020, which found a large protective effect of nocturnal dosing on cardiovascular events, and attracted much media attention. But this study has subsequently attracted criticism, with an “expression of concern” and a commentary raising several questions. 

And a systematic review from the International Society of Hypertension published earlier this month concludes that previous trials of bedtime antihypertensive dosing had “major flaws.”

The review notes that three ongoing, well-designed, prospective, randomized controlled outcome trials are expected to provide high-quality data on the efficacy and safety of evening or bedtime versus morning drug dosing.

“Until that information is available, preferred use of bedtime drug dosing of antihypertensive drugs should not be routinely recommended in clinical practice. Complete 24-h control of BP should be targeted using readily available, long-acting antihypertensive medications as monotherapy or combinations administered in a single morning dose,” it concludes.

On the new TIME results, lead author of the ISH review, George Stergiou, MD, commented: “The benefits of bedtime dosing were not confirmed – as we well expected. So, I think bedtime drug dosing should not be routinely recommended in clinical practice.”

Although the TIME trial did not show any harms with bedtime dose, Dr. Stergiou added, “I am not too happy with their conclusion that patients should do as they wish. The vast majority of well-conducted outcomes studies which we use to guide the treatment of hypertension administered all drugs in the morning.”

One of the authors of the commentary criticizing the Hygia trial, Sverre E. Kjeldsen, MD, University of Oslo, said in an interview that the TIME trial was an important study, far more reliable than the Hygia study, and the results were as expected.

“From a scientific point of view, patients have a choice as to when to take their medication, but we strongly recommend taking blood pressure meds in the morning. Adherence is proven to be worse at bedtime. However, physicians may still consider bedtime dosing in patients proven to have high night-time blood pressure,” Dr. Kjeldsen added.

Lead investigator of the Hygia study, Ramón C. Hermida, PhD, University of Vigo (Spain), told this news organization he and his coauthors are standing by their results.

“The design and conduct of the TIME trial does not comply with the quality requirements listed in the guidelines by the International Society for Chronobiology for conducting chronotherapy trials in hypertension, and the results are not in line with the reported findings of multiple clinical trials on the effects of timed hypertension treatment on blood pressure control and circadian pattern regulation, kidney function, and cardiac pathology,” Dr. Hermida said.

Chair of an ESC press conference on the TIME study, Steen Dalby Kristensen, MD, Aarhus University Hospital, Skejby, Denmark, said he thought the trial was “very well done.”

The TIME results, he said, “are quite clear, whether you take your blood pressure tablets in the morning or the evening it makes no difference for the hard outcomes that we fear in patients with hypertension.  

“I think that this solves a question that we’ve had for a long time now,” he commented. “Even though there were some changes in the blood pressure measured in the evening or in the morning it doesn’t seem to matter in terms of clinical events. This means that life might be a bit easier for patients in that they can choose when they take their medication at the time most convenient to them.  

“I don’t know why previous studies suggested such a big benefit of evening dosing,” he added. “I would say the TIME trial is a more definitive result. It is a very important trial.”

Dipti Itchhaporia, MD, University of California, Irvine, and immediate past president of the American College of Cardiology, agreed that the TIME study was well conducted.

“On the basis of these results I wouldn’t recommend a specific time,” she said. “That’s kind of a relief, as it can be difficult to always take medications at a set time and this gives patients more flexibility.”

She suggested a possible alternative approach for patients taking more than one drug – taking one in the morning and the other in the evening. “That might give better 24-hour coverage.”

The study was funded by the British Heart Foundation. Dr. MacDonald has reported receiving research funding from Novartis and consulting fees from Novartis and AstraZeneca.

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

BARCELONA – Treatment of patients with chronic heart failure with sacubitril/valsartan (Entresto), a mainstay agent for people with this disorder, produced no hint of incremental adverse cognitive effects during 3 years of treatment in a prospective, controlled, multicenter study with nearly 600 patients, although some experts note that possible adverse cognitive effects of sacubitril were not an issue for many heart failure clinicians, even before the study ran.

The potential for an adverse effect of sacubitril on cognition had arisen as a hypothetical concern because sacubitril inhibits the human enzyme neprilysin. This activity results in beneficial effects for patients with heart failure by increasing levels of several endogenous vasoactive peptides. But neprilysin also degrades amyloid beta peptides and so inhibition of this enzyme could possibly result in accumulation of amyloid peptides in the brain with potential neurotoxic effects, which raised concern among some cardiologists and patients that sacubitril/valsartan could hasten cognitive decline.

Catherine Hackett/MDedge News

Results from the new study, PERSPECTIVE, showed “no evidence that neprilysin inhibition increased the risk of cognitive impairment due to the accumulation of beta amyloid” in patients with heart failure with either mid-range or preserved ejection fraction,” John McMurray, MD, said at the annual congress of the European Society of Cardiology.

Dr. McMurray, professor of medical cardiology at the University of Glasgow, highlighted that the study enrolled only patients with heart failure with a left ventricular ejection fraction of greater than 40% because the study designers considered it “unethical” to withhold treatment with sacubitril/valsartan from patients with an ejection fraction of 40% or less (heart failure with reduced ejection fraction, HFrEF), whereas “no mandate” exists in current treatment guidelines for using sacubitril/valsartan in patients with heart failure and higher ejection fractions. He added that he could see no reason why the results seen in patients with higher ejection fractions would not also apply to those with HFrEF.
 

Reassuring results, but cost still a drag on uptake

“This was a well-designed trial” with results that are “very reassuring” for a lack of harm from sacubitril/valsartan, commented Biykem Bozkurt, MD, PhD, the study’s designated discussant and professor of medicine at Baylor College of Medicine, Houston. The findings “solidify the lack of risk and are very exciting for the heart failure community because the question has bothered a large number of people, especially older patients” with heart failure.

Catherine Hackett/MDedge News

Following these results, “hopefully more patients with heart failure will receive” sacubitril/valsartan, agreed Dr. McMurray, but he added the caveat that the relatively high cost of the agent (which has a U.S. list price of roughly $6,000/year) has been the primary barrier to wider uptake of the drug for patients with heart failure. Treatment with sacubitril/valsartan is recommended in several society guidelines as a core intervention for patients with HFrEF and as a treatment option for patients with heart failure and higher ejection fractions.

“Cost remains the single biggest deterrent for use” of sacubitril/valsartan, agreed Dipti N. Itchhaporia, MD, director of disease management at the Hoag Heart and Vascular Institute in Newport Beach, Calif. “Concerns about cognitive impairment has not been why people have not been using sacubitril/valsartan,” Dr. Itchhaporia commented in an interview.

PERSPECTIVE enrolled patients with heart failure with an ejection fraction greater than 40% and at least 60 years old at any of 137 sites in 20 countries, with about a third of enrolled patients coming from U.S. centers. The study, which ran enrollment during January 2017–May 2019, excluded people with clinically discernible cognitive impairment at the time of entry.

Researchers randomized patients to either a standard regimen of sacubitril/valsartan (295) or valsartan (297) on top of their background treatment, with most patients also receiving a beta-blocker, a diuretic, and a statin. The enrolled patients averaged about 72 years of age, and more than one-third were at least 75 years old.

The study’s primary endpoint was the performance of these patients in seven different tests of cognitive function using a proprietary metric, the CogState Global Cognitive Composite Score, measured at baseline and then every 6 months during follow-up designed to run for 3 years on treatment (the researchers collected data for at least 30 months of follow-up from 71%-73% of enrolled patients). Average changes in these scores over time tracked nearly the same in both treatment arms and met the study’s prespecified criteria for noninferiority of the sacubitril valsartan treatment, Dr. McMurray reported. The results also showed that roughly 60% of patients in both arms had “some degree of cognitive impairment” during follow-up.

A secondary outcome measure used PET imaging to quantify cerebral accumulation of beta amyloid, and again the results met the study’s prespecified threshold for noninferiority for the patients treated with sacubitril/valsartan, said Dr. McMurray.

Another concern raised by some experts was the relatively brief follow-up of 3 years, and the complexity of heart failure patients who could face several other causes of cognitive decline. The findings “help reassure, but 3 years is not long enough, and I’m not sure the study eliminated all the other possible variables,” commented Dr. Itchhaporia.

But Dr. McMurray contended that 3 years represents robust follow-up in patients with heart failure who notoriously have limited life expectancy following their diagnosis. “Three years is a long time for patients with heart failure.”

The findings also raise the prospect of developing sacubitril/valsartan as an antihypertensive treatment, an indication that has been avoided until now because of the uncertain cognitive effects of the agent and the need for prolonged use when the treated disorder is hypertension instead of heart failure.

PERSPECTIVE was funded by Novartis, the company that markets sacubitril/valsartan (Entresto). Dr. McMurray has received consulting and lecture fees from Novartis and he and his institution have received research funding from Novartis. Dr. Bozkurt has been a consultant to numerous companies but has no relationship with Novartis. Dr. Itchhaporia had no disclosures.

BARCELONA – Treatment of patients with chronic heart failure with sacubitril/valsartan (Entresto), a mainstay agent for people with this disorder, produced no hint of incremental adverse cognitive effects during 3 years of treatment in a prospective, controlled, multicenter study with nearly 600 patients, although some experts note that possible adverse cognitive effects of sacubitril were not an issue for many heart failure clinicians, even before the study ran.

The potential for an adverse effect of sacubitril on cognition had arisen as a hypothetical concern because sacubitril inhibits the human enzyme neprilysin. This activity results in beneficial effects for patients with heart failure by increasing levels of several endogenous vasoactive peptides. But neprilysin also degrades amyloid beta peptides and so inhibition of this enzyme could possibly result in accumulation of amyloid peptides in the brain with potential neurotoxic effects, which raised concern among some cardiologists and patients that sacubitril/valsartan could hasten cognitive decline.

Catherine Hackett/MDedge News

Results from the new study, PERSPECTIVE, showed “no evidence that neprilysin inhibition increased the risk of cognitive impairment due to the accumulation of beta amyloid” in patients with heart failure with either mid-range or preserved ejection fraction,” John McMurray, MD, said at the annual congress of the European Society of Cardiology.

Dr. McMurray, professor of medical cardiology at the University of Glasgow, highlighted that the study enrolled only patients with heart failure with a left ventricular ejection fraction of greater than 40% because the study designers considered it “unethical” to withhold treatment with sacubitril/valsartan from patients with an ejection fraction of 40% or less (heart failure with reduced ejection fraction, HFrEF), whereas “no mandate” exists in current treatment guidelines for using sacubitril/valsartan in patients with heart failure and higher ejection fractions. He added that he could see no reason why the results seen in patients with higher ejection fractions would not also apply to those with HFrEF.
 

Reassuring results, but cost still a drag on uptake

“This was a well-designed trial” with results that are “very reassuring” for a lack of harm from sacubitril/valsartan, commented Biykem Bozkurt, MD, PhD, the study’s designated discussant and professor of medicine at Baylor College of Medicine, Houston. The findings “solidify the lack of risk and are very exciting for the heart failure community because the question has bothered a large number of people, especially older patients” with heart failure.

Catherine Hackett/MDedge News

Following these results, “hopefully more patients with heart failure will receive” sacubitril/valsartan, agreed Dr. McMurray, but he added the caveat that the relatively high cost of the agent (which has a U.S. list price of roughly $6,000/year) has been the primary barrier to wider uptake of the drug for patients with heart failure. Treatment with sacubitril/valsartan is recommended in several society guidelines as a core intervention for patients with HFrEF and as a treatment option for patients with heart failure and higher ejection fractions.

“Cost remains the single biggest deterrent for use” of sacubitril/valsartan, agreed Dipti N. Itchhaporia, MD, director of disease management at the Hoag Heart and Vascular Institute in Newport Beach, Calif. “Concerns about cognitive impairment has not been why people have not been using sacubitril/valsartan,” Dr. Itchhaporia commented in an interview.

PERSPECTIVE enrolled patients with heart failure with an ejection fraction greater than 40% and at least 60 years old at any of 137 sites in 20 countries, with about a third of enrolled patients coming from U.S. centers. The study, which ran enrollment during January 2017–May 2019, excluded people with clinically discernible cognitive impairment at the time of entry.

Researchers randomized patients to either a standard regimen of sacubitril/valsartan (295) or valsartan (297) on top of their background treatment, with most patients also receiving a beta-blocker, a diuretic, and a statin. The enrolled patients averaged about 72 years of age, and more than one-third were at least 75 years old.

The study’s primary endpoint was the performance of these patients in seven different tests of cognitive function using a proprietary metric, the CogState Global Cognitive Composite Score, measured at baseline and then every 6 months during follow-up designed to run for 3 years on treatment (the researchers collected data for at least 30 months of follow-up from 71%-73% of enrolled patients). Average changes in these scores over time tracked nearly the same in both treatment arms and met the study’s prespecified criteria for noninferiority of the sacubitril valsartan treatment, Dr. McMurray reported. The results also showed that roughly 60% of patients in both arms had “some degree of cognitive impairment” during follow-up.

A secondary outcome measure used PET imaging to quantify cerebral accumulation of beta amyloid, and again the results met the study’s prespecified threshold for noninferiority for the patients treated with sacubitril/valsartan, said Dr. McMurray.

Another concern raised by some experts was the relatively brief follow-up of 3 years, and the complexity of heart failure patients who could face several other causes of cognitive decline. The findings “help reassure, but 3 years is not long enough, and I’m not sure the study eliminated all the other possible variables,” commented Dr. Itchhaporia.

But Dr. McMurray contended that 3 years represents robust follow-up in patients with heart failure who notoriously have limited life expectancy following their diagnosis. “Three years is a long time for patients with heart failure.”

The findings also raise the prospect of developing sacubitril/valsartan as an antihypertensive treatment, an indication that has been avoided until now because of the uncertain cognitive effects of the agent and the need for prolonged use when the treated disorder is hypertension instead of heart failure.

PERSPECTIVE was funded by Novartis, the company that markets sacubitril/valsartan (Entresto). Dr. McMurray has received consulting and lecture fees from Novartis and he and his institution have received research funding from Novartis. Dr. Bozkurt has been a consultant to numerous companies but has no relationship with Novartis. Dr. Itchhaporia had no disclosures.

BARCELONA – Treatment of patients with chronic heart failure with sacubitril/valsartan (Entresto), a mainstay agent for people with this disorder, produced no hint of incremental adverse cognitive effects during 3 years of treatment in a prospective, controlled, multicenter study with nearly 600 patients, although some experts note that possible adverse cognitive effects of sacubitril were not an issue for many heart failure clinicians, even before the study ran.

The potential for an adverse effect of sacubitril on cognition had arisen as a hypothetical concern because sacubitril inhibits the human enzyme neprilysin. This activity results in beneficial effects for patients with heart failure by increasing levels of several endogenous vasoactive peptides. But neprilysin also degrades amyloid beta peptides and so inhibition of this enzyme could possibly result in accumulation of amyloid peptides in the brain with potential neurotoxic effects, which raised concern among some cardiologists and patients that sacubitril/valsartan could hasten cognitive decline.

Catherine Hackett/MDedge News

Results from the new study, PERSPECTIVE, showed “no evidence that neprilysin inhibition increased the risk of cognitive impairment due to the accumulation of beta amyloid” in patients with heart failure with either mid-range or preserved ejection fraction,” John McMurray, MD, said at the annual congress of the European Society of Cardiology.

Dr. McMurray, professor of medical cardiology at the University of Glasgow, highlighted that the study enrolled only patients with heart failure with a left ventricular ejection fraction of greater than 40% because the study designers considered it “unethical” to withhold treatment with sacubitril/valsartan from patients with an ejection fraction of 40% or less (heart failure with reduced ejection fraction, HFrEF), whereas “no mandate” exists in current treatment guidelines for using sacubitril/valsartan in patients with heart failure and higher ejection fractions. He added that he could see no reason why the results seen in patients with higher ejection fractions would not also apply to those with HFrEF.
 

Reassuring results, but cost still a drag on uptake

“This was a well-designed trial” with results that are “very reassuring” for a lack of harm from sacubitril/valsartan, commented Biykem Bozkurt, MD, PhD, the study’s designated discussant and professor of medicine at Baylor College of Medicine, Houston. The findings “solidify the lack of risk and are very exciting for the heart failure community because the question has bothered a large number of people, especially older patients” with heart failure.

Catherine Hackett/MDedge News

Following these results, “hopefully more patients with heart failure will receive” sacubitril/valsartan, agreed Dr. McMurray, but he added the caveat that the relatively high cost of the agent (which has a U.S. list price of roughly $6,000/year) has been the primary barrier to wider uptake of the drug for patients with heart failure. Treatment with sacubitril/valsartan is recommended in several society guidelines as a core intervention for patients with HFrEF and as a treatment option for patients with heart failure and higher ejection fractions.

“Cost remains the single biggest deterrent for use” of sacubitril/valsartan, agreed Dipti N. Itchhaporia, MD, director of disease management at the Hoag Heart and Vascular Institute in Newport Beach, Calif. “Concerns about cognitive impairment has not been why people have not been using sacubitril/valsartan,” Dr. Itchhaporia commented in an interview.

PERSPECTIVE enrolled patients with heart failure with an ejection fraction greater than 40% and at least 60 years old at any of 137 sites in 20 countries, with about a third of enrolled patients coming from U.S. centers. The study, which ran enrollment during January 2017–May 2019, excluded people with clinically discernible cognitive impairment at the time of entry.

Researchers randomized patients to either a standard regimen of sacubitril/valsartan (295) or valsartan (297) on top of their background treatment, with most patients also receiving a beta-blocker, a diuretic, and a statin. The enrolled patients averaged about 72 years of age, and more than one-third were at least 75 years old.

The study’s primary endpoint was the performance of these patients in seven different tests of cognitive function using a proprietary metric, the CogState Global Cognitive Composite Score, measured at baseline and then every 6 months during follow-up designed to run for 3 years on treatment (the researchers collected data for at least 30 months of follow-up from 71%-73% of enrolled patients). Average changes in these scores over time tracked nearly the same in both treatment arms and met the study’s prespecified criteria for noninferiority of the sacubitril valsartan treatment, Dr. McMurray reported. The results also showed that roughly 60% of patients in both arms had “some degree of cognitive impairment” during follow-up.

A secondary outcome measure used PET imaging to quantify cerebral accumulation of beta amyloid, and again the results met the study’s prespecified threshold for noninferiority for the patients treated with sacubitril/valsartan, said Dr. McMurray.

Another concern raised by some experts was the relatively brief follow-up of 3 years, and the complexity of heart failure patients who could face several other causes of cognitive decline. The findings “help reassure, but 3 years is not long enough, and I’m not sure the study eliminated all the other possible variables,” commented Dr. Itchhaporia.

But Dr. McMurray contended that 3 years represents robust follow-up in patients with heart failure who notoriously have limited life expectancy following their diagnosis. “Three years is a long time for patients with heart failure.”

The findings also raise the prospect of developing sacubitril/valsartan as an antihypertensive treatment, an indication that has been avoided until now because of the uncertain cognitive effects of the agent and the need for prolonged use when the treated disorder is hypertension instead of heart failure.

PERSPECTIVE was funded by Novartis, the company that markets sacubitril/valsartan (Entresto). Dr. McMurray has received consulting and lecture fees from Novartis and he and his institution have received research funding from Novartis. Dr. Bozkurt has been a consultant to numerous companies but has no relationship with Novartis. Dr. Itchhaporia had no disclosures.

The study covered in this summary was published on ResearchSquare.com as a preprint and has not yet been peer reviewed.

Key takeaway

• High-dose furosemide after cardiac surgery is associated with increased mortality and other adverse outcomes.

Why this matters

• The influence of furosemide on prognosis after cardiac surgery is not fully understood.
• The current findings suggest that high-dose furosemide after cardiac surgery is associated with increased risk for death and other adverse events and therefore should be used cautiously in that setting.

Study design

• The retrospective cohort of 6,752 cardiac surgery patients was divided into two groups according to average daily furosemide dosage after cardiac surgery: less than 20 mg (low-dose group, n = 6,033) and at least 20 mg (high-dose group, n = 719).
• The group were compared for total furosemide dose, total furosemide dose of at least 200 mg, total dose of furosemide by patient weight, and average daily furosemide dose of at least 20 mg.
• The primary outcomes were in-hospital mortality and mortality at 1 year after cardiac surgery. Secondary outcomes were length of hospital stay of at least 14 days, length of ICU stay of at least 3 days, and mechanical ventilation for at least 48 hours.
• The study excluded patients aged younger than 18 whose weight data was missing or who had more than 5% of their data missing.

Key results

• Patients in the high-dose furosemide group tended to be older and have a higher body mass index (BMI) and higher rates of diabetes, chronic pulmonary diseases, heart failure, renal failure, blood transfusion, vasopressor use, and valvular surgery.
• They also tended have higher white cell counts and higher levels of blood urea nitrogen, creatinine, glucose, and lactate.
• Those in the high-dose group also were on vasopressors and ventilatory support longer.
• In adjusted multivariate analysis, increased in-hospital mortality was associated with average daily furosemide dose, average daily dose of at least 20 mg/d, and total dose of at least 200 mg.
• Increased mortality at 1 year was associated with total furosemide dose and average daily furosemide dose.
• Significant multivariate predictors of hospital stay of at least 14 days, length of ICU stay of at least 3 days, and mechanical ventilation for at least 48 hours after cardiac surgery included total furosemide dose, total dose by weight, average daily furosemide dose of at least 20 mg/d, and total dose of at least 200 mg.
• In subgroup analyses, average daily furosemide dose of at least 20 mg/d significantly increased risk for in-hospital mortality among patients younger than 60 years or with BMI of at least 28 who received vasopressors or blood transfusions, those with renal failure, and those with heart failure not involving congestion.

Limitations

• No limitations were discussed.

Disclosures

• The study was supported by grants from the National Natural Science Foundation of China, China Postdoctoral Science Foundation, and Jiangsu Postdoctoral Science Foundation.
• The authors declared that they have no competing interests.

This is a summary of a preprint research study, “Association between furosemide administration and outcomes in patients undergoing cardiac surgery,” from Jinghang Li, First Affiliated Hospital of Nanjing (China) Medical University, and colleagues on published on ResearchSquare.com. This study has not yet been peer reviewed. The full text of the study can be found on ResearchSquare.com. A version of this article first appeared on Medscape.com.

The study covered in this summary was published on ResearchSquare.com as a preprint and has not yet been peer reviewed.

Key takeaway

• High-dose furosemide after cardiac surgery is associated with increased mortality and other adverse outcomes.

Why this matters

• The influence of furosemide on prognosis after cardiac surgery is not fully understood.
• The current findings suggest that high-dose furosemide after cardiac surgery is associated with increased risk for death and other adverse events and therefore should be used cautiously in that setting.

Study design

• The retrospective cohort of 6,752 cardiac surgery patients was divided into two groups according to average daily furosemide dosage after cardiac surgery: less than 20 mg (low-dose group, n = 6,033) and at least 20 mg (high-dose group, n = 719).
• The group were compared for total furosemide dose, total furosemide dose of at least 200 mg, total dose of furosemide by patient weight, and average daily furosemide dose of at least 20 mg.
• The primary outcomes were in-hospital mortality and mortality at 1 year after cardiac surgery. Secondary outcomes were length of hospital stay of at least 14 days, length of ICU stay of at least 3 days, and mechanical ventilation for at least 48 hours.
• The study excluded patients aged younger than 18 whose weight data was missing or who had more than 5% of their data missing.

Key results

• Patients in the high-dose furosemide group tended to be older and have a higher body mass index (BMI) and higher rates of diabetes, chronic pulmonary diseases, heart failure, renal failure, blood transfusion, vasopressor use, and valvular surgery.
• They also tended have higher white cell counts and higher levels of blood urea nitrogen, creatinine, glucose, and lactate.
• Those in the high-dose group also were on vasopressors and ventilatory support longer.
• In adjusted multivariate analysis, increased in-hospital mortality was associated with average daily furosemide dose, average daily dose of at least 20 mg/d, and total dose of at least 200 mg.
• Increased mortality at 1 year was associated with total furosemide dose and average daily furosemide dose.
• Significant multivariate predictors of hospital stay of at least 14 days, length of ICU stay of at least 3 days, and mechanical ventilation for at least 48 hours after cardiac surgery included total furosemide dose, total dose by weight, average daily furosemide dose of at least 20 mg/d, and total dose of at least 200 mg.
• In subgroup analyses, average daily furosemide dose of at least 20 mg/d significantly increased risk for in-hospital mortality among patients younger than 60 years or with BMI of at least 28 who received vasopressors or blood transfusions, those with renal failure, and those with heart failure not involving congestion.

Limitations

• No limitations were discussed.

Disclosures

• The study was supported by grants from the National Natural Science Foundation of China, China Postdoctoral Science Foundation, and Jiangsu Postdoctoral Science Foundation.
• The authors declared that they have no competing interests.

This is a summary of a preprint research study, “Association between furosemide administration and outcomes in patients undergoing cardiac surgery,” from Jinghang Li, First Affiliated Hospital of Nanjing (China) Medical University, and colleagues on published on ResearchSquare.com. This study has not yet been peer reviewed. The full text of the study can be found on ResearchSquare.com. A version of this article first appeared on Medscape.com.

The study covered in this summary was published on ResearchSquare.com as a preprint and has not yet been peer reviewed.

Key takeaway

• High-dose furosemide after cardiac surgery is associated with increased mortality and other adverse outcomes.

Why this matters

• The influence of furosemide on prognosis after cardiac surgery is not fully understood.
• The current findings suggest that high-dose furosemide after cardiac surgery is associated with increased risk for death and other adverse events and therefore should be used cautiously in that setting.

Study design

• The retrospective cohort of 6,752 cardiac surgery patients was divided into two groups according to average daily furosemide dosage after cardiac surgery: less than 20 mg (low-dose group, n = 6,033) and at least 20 mg (high-dose group, n = 719).
• The group were compared for total furosemide dose, total furosemide dose of at least 200 mg, total dose of furosemide by patient weight, and average daily furosemide dose of at least 20 mg.
• The primary outcomes were in-hospital mortality and mortality at 1 year after cardiac surgery. Secondary outcomes were length of hospital stay of at least 14 days, length of ICU stay of at least 3 days, and mechanical ventilation for at least 48 hours.
• The study excluded patients aged younger than 18 whose weight data was missing or who had more than 5% of their data missing.

Key results

• Patients in the high-dose furosemide group tended to be older and have a higher body mass index (BMI) and higher rates of diabetes, chronic pulmonary diseases, heart failure, renal failure, blood transfusion, vasopressor use, and valvular surgery.
• They also tended have higher white cell counts and higher levels of blood urea nitrogen, creatinine, glucose, and lactate.
• Those in the high-dose group also were on vasopressors and ventilatory support longer.
• In adjusted multivariate analysis, increased in-hospital mortality was associated with average daily furosemide dose, average daily dose of at least 20 mg/d, and total dose of at least 200 mg.
• Increased mortality at 1 year was associated with total furosemide dose and average daily furosemide dose.
• Significant multivariate predictors of hospital stay of at least 14 days, length of ICU stay of at least 3 days, and mechanical ventilation for at least 48 hours after cardiac surgery included total furosemide dose, total dose by weight, average daily furosemide dose of at least 20 mg/d, and total dose of at least 200 mg.
• In subgroup analyses, average daily furosemide dose of at least 20 mg/d significantly increased risk for in-hospital mortality among patients younger than 60 years or with BMI of at least 28 who received vasopressors or blood transfusions, those with renal failure, and those with heart failure not involving congestion.

Limitations

• No limitations were discussed.

Disclosures

• The study was supported by grants from the National Natural Science Foundation of China, China Postdoctoral Science Foundation, and Jiangsu Postdoctoral Science Foundation.
• The authors declared that they have no competing interests.

This is a summary of a preprint research study, “Association between furosemide administration and outcomes in patients undergoing cardiac surgery,” from Jinghang Li, First Affiliated Hospital of Nanjing (China) Medical University, and colleagues on published on ResearchSquare.com. This study has not yet been peer reviewed. The full text of the study can be found on ResearchSquare.com. A version of this article first appeared on Medscape.com.

SEOUL, South Korea – Menopause before age 40 is associated with elevated risk of heart failure and atrial fibrillation, according to a study published in European Heart Journal, from the European Society of Cardiology (ESC). The study of more than 1.4 million women revealed that the younger the age at menopause, the higher the risk of heart failure and atrial fibrillation.

“Women with premature menopause should be aware that they may be more likely to develop heart failure or atrial fibrillation than their peers,” said study author Ga Eun Nam, MD, PhD, of Korea University College of Medicine, Seoul. “This may be good motivation to improve lifestyle habits known to be linked with heart disease, such as quitting smoking and exercising.”

Cardiovascular disease typically occurs up to 10 years later in women than men. Premenopausal women are thought to benefit from estrogen’s protective effect on the cardiovascular system. The cessation of menstruation and subsequent decline of estrogen levels may make women more vulnerable to cardiovascular disease.
 

A national population

Premature menopause affects 1% of women younger than 40 years, the ESC press release stated. Prior studies have found a link between premature (before age 40 years) and early (before age 45 years) menopause and cardiovascular disease overall, but the evidence for heart failure or atrial fibrillation alone is limited. This study examined the associations between premature menopause, age at menopause, and incident heart failure and atrial fibrillation. Data were obtained from the Korean National Health Insurance System (NHIS), which provides health screening at least every 2 years and includes 97% of the population.

The study included 1,401,175 postmenopausal women aged 30 years and older who completed the NHIS health checkup in 2009. Participants were monitored until the end of 2018 for new-onset heart failure and atrial fibrillation. Information was collected on demographics, health behaviors, and reproductive factors, including age at menopause and use of hormone replacement therapy (HRT). Age at menopause was split into four categories: younger than 40 years, 40-44 years, 45-49 years, and 50 years or older. Premature menopause was defined as having the final menstrual period before age 40 years.

Some 28,111 (2%) participants had a history of premature menopause. For these women, the average age at menopause was 36.7 years. The average age at study enrollment for women with and for those without a history of premature menopause was 60 and 61.5 years, respectively. During an average follow-up of 9.1 years, 42,699 (3.0%) developed heart failure, and 44,834 (3.2%) developed atrial fibrillation.

The researchers analyzed the association between history of premature menopause and incident heart failure and atrial fibrillation after adjusting for age, smoking, alcohol use, physical activity, income, body mass index, hypertension, type 2 diabetes, dyslipidemia, chronic kidney disease, coronary heart disease, HRT, and age at menarche. Women who experienced premature menopause had a 33% higher risk for heart failure and 9% higher risk for atrial fibrillation, compared with those who did not.
 

Reproductive history

The researchers then analyzed the associations between age at menopause and incidence of heart failure and atrial fibrillation after adjusting for the same factors as in the previous analyses. The risk for incident heart failure increased as the age at menopause decreased. Compared with women aged 50 years and older at menopause, those aged 45-49 years, 40-44 years, and younger than 40 years at menopause had 11%, 23%, and 39% greater risk for incident heart failure, respectively. Similarly, the risk for incident atrial fibrillation increased as the age at menopause decreased; the risk was 4%, 10%, and 11% higher for those aged 45-49 years, 40-44 years, and younger than 40 years at menopause, respectively, compared with women aged 50 years and older at menopause.

The authors said that several factors may explain the associations between menopausal age, heart failure, and atrial fibrillation, such as the drop in estrogen levels and changes in body fat distribution.

Dr. Nam concluded, “The misconception that heart disease primarily affects men has meant that sex-specific risk factors have been largely ignored. Evidence is growing that undergoing menopause before the age of 40 years may increase the likelihood of heart disease later in life. Our study indicates that reproductive history should be routinely considered in addition to traditional risk factors such as smoking when evaluating the future likelihood of heart failure and atrial fibrillation.”

A version of this article appeared on Medscape.com. This article was translated from the Medscape French edition.

SEOUL, South Korea – Menopause before age 40 is associated with elevated risk of heart failure and atrial fibrillation, according to a study published in European Heart Journal, from the European Society of Cardiology (ESC). The study of more than 1.4 million women revealed that the younger the age at menopause, the higher the risk of heart failure and atrial fibrillation.

“Women with premature menopause should be aware that they may be more likely to develop heart failure or atrial fibrillation than their peers,” said study author Ga Eun Nam, MD, PhD, of Korea University College of Medicine, Seoul. “This may be good motivation to improve lifestyle habits known to be linked with heart disease, such as quitting smoking and exercising.”

Cardiovascular disease typically occurs up to 10 years later in women than men. Premenopausal women are thought to benefit from estrogen’s protective effect on the cardiovascular system. The cessation of menstruation and subsequent decline of estrogen levels may make women more vulnerable to cardiovascular disease.
 

A national population

Premature menopause affects 1% of women younger than 40 years, the ESC press release stated. Prior studies have found a link between premature (before age 40 years) and early (before age 45 years) menopause and cardiovascular disease overall, but the evidence for heart failure or atrial fibrillation alone is limited. This study examined the associations between premature menopause, age at menopause, and incident heart failure and atrial fibrillation. Data were obtained from the Korean National Health Insurance System (NHIS), which provides health screening at least every 2 years and includes 97% of the population.

The study included 1,401,175 postmenopausal women aged 30 years and older who completed the NHIS health checkup in 2009. Participants were monitored until the end of 2018 for new-onset heart failure and atrial fibrillation. Information was collected on demographics, health behaviors, and reproductive factors, including age at menopause and use of hormone replacement therapy (HRT). Age at menopause was split into four categories: younger than 40 years, 40-44 years, 45-49 years, and 50 years or older. Premature menopause was defined as having the final menstrual period before age 40 years.

Some 28,111 (2%) participants had a history of premature menopause. For these women, the average age at menopause was 36.7 years. The average age at study enrollment for women with and for those without a history of premature menopause was 60 and 61.5 years, respectively. During an average follow-up of 9.1 years, 42,699 (3.0%) developed heart failure, and 44,834 (3.2%) developed atrial fibrillation.

The researchers analyzed the association between history of premature menopause and incident heart failure and atrial fibrillation after adjusting for age, smoking, alcohol use, physical activity, income, body mass index, hypertension, type 2 diabetes, dyslipidemia, chronic kidney disease, coronary heart disease, HRT, and age at menarche. Women who experienced premature menopause had a 33% higher risk for heart failure and 9% higher risk for atrial fibrillation, compared with those who did not.
 

Reproductive history

The researchers then analyzed the associations between age at menopause and incidence of heart failure and atrial fibrillation after adjusting for the same factors as in the previous analyses. The risk for incident heart failure increased as the age at menopause decreased. Compared with women aged 50 years and older at menopause, those aged 45-49 years, 40-44 years, and younger than 40 years at menopause had 11%, 23%, and 39% greater risk for incident heart failure, respectively. Similarly, the risk for incident atrial fibrillation increased as the age at menopause decreased; the risk was 4%, 10%, and 11% higher for those aged 45-49 years, 40-44 years, and younger than 40 years at menopause, respectively, compared with women aged 50 years and older at menopause.

The authors said that several factors may explain the associations between menopausal age, heart failure, and atrial fibrillation, such as the drop in estrogen levels and changes in body fat distribution.

Dr. Nam concluded, “The misconception that heart disease primarily affects men has meant that sex-specific risk factors have been largely ignored. Evidence is growing that undergoing menopause before the age of 40 years may increase the likelihood of heart disease later in life. Our study indicates that reproductive history should be routinely considered in addition to traditional risk factors such as smoking when evaluating the future likelihood of heart failure and atrial fibrillation.”

A version of this article appeared on Medscape.com. This article was translated from the Medscape French edition.

SEOUL, South Korea – Menopause before age 40 is associated with elevated risk of heart failure and atrial fibrillation, according to a study published in European Heart Journal, from the European Society of Cardiology (ESC). The study of more than 1.4 million women revealed that the younger the age at menopause, the higher the risk of heart failure and atrial fibrillation.

“Women with premature menopause should be aware that they may be more likely to develop heart failure or atrial fibrillation than their peers,” said study author Ga Eun Nam, MD, PhD, of Korea University College of Medicine, Seoul. “This may be good motivation to improve lifestyle habits known to be linked with heart disease, such as quitting smoking and exercising.”

Cardiovascular disease typically occurs up to 10 years later in women than men. Premenopausal women are thought to benefit from estrogen’s protective effect on the cardiovascular system. The cessation of menstruation and subsequent decline of estrogen levels may make women more vulnerable to cardiovascular disease.
 

A national population

Premature menopause affects 1% of women younger than 40 years, the ESC press release stated. Prior studies have found a link between premature (before age 40 years) and early (before age 45 years) menopause and cardiovascular disease overall, but the evidence for heart failure or atrial fibrillation alone is limited. This study examined the associations between premature menopause, age at menopause, and incident heart failure and atrial fibrillation. Data were obtained from the Korean National Health Insurance System (NHIS), which provides health screening at least every 2 years and includes 97% of the population.

The study included 1,401,175 postmenopausal women aged 30 years and older who completed the NHIS health checkup in 2009. Participants were monitored until the end of 2018 for new-onset heart failure and atrial fibrillation. Information was collected on demographics, health behaviors, and reproductive factors, including age at menopause and use of hormone replacement therapy (HRT). Age at menopause was split into four categories: younger than 40 years, 40-44 years, 45-49 years, and 50 years or older. Premature menopause was defined as having the final menstrual period before age 40 years.

Some 28,111 (2%) participants had a history of premature menopause. For these women, the average age at menopause was 36.7 years. The average age at study enrollment for women with and for those without a history of premature menopause was 60 and 61.5 years, respectively. During an average follow-up of 9.1 years, 42,699 (3.0%) developed heart failure, and 44,834 (3.2%) developed atrial fibrillation.

The researchers analyzed the association between history of premature menopause and incident heart failure and atrial fibrillation after adjusting for age, smoking, alcohol use, physical activity, income, body mass index, hypertension, type 2 diabetes, dyslipidemia, chronic kidney disease, coronary heart disease, HRT, and age at menarche. Women who experienced premature menopause had a 33% higher risk for heart failure and 9% higher risk for atrial fibrillation, compared with those who did not.
 

Reproductive history

The researchers then analyzed the associations between age at menopause and incidence of heart failure and atrial fibrillation after adjusting for the same factors as in the previous analyses. The risk for incident heart failure increased as the age at menopause decreased. Compared with women aged 50 years and older at menopause, those aged 45-49 years, 40-44 years, and younger than 40 years at menopause had 11%, 23%, and 39% greater risk for incident heart failure, respectively. Similarly, the risk for incident atrial fibrillation increased as the age at menopause decreased; the risk was 4%, 10%, and 11% higher for those aged 45-49 years, 40-44 years, and younger than 40 years at menopause, respectively, compared with women aged 50 years and older at menopause.

The authors said that several factors may explain the associations between menopausal age, heart failure, and atrial fibrillation, such as the drop in estrogen levels and changes in body fat distribution.

Dr. Nam concluded, “The misconception that heart disease primarily affects men has meant that sex-specific risk factors have been largely ignored. Evidence is growing that undergoing menopause before the age of 40 years may increase the likelihood of heart disease later in life. Our study indicates that reproductive history should be routinely considered in addition to traditional risk factors such as smoking when evaluating the future likelihood of heart failure and atrial fibrillation.”

A version of this article appeared on Medscape.com. This article was translated from the Medscape French edition.

People with diabetes who take nonsteroidal anti-inflammatory drugs even on a short-term basis may have about a 50% greater risk of developing heart failure, according to results from a national registry study of more than 330,000 patients to be presented at the annual congress of the European Society of Cardiology.

“According to data from this study, even short-term NSAID use – within 28 days – in patients with type 2 diabetes mellitus are associated with an increased risk of first-time heart failure hospitalization,” lead author Anders Holt, MD, said in an interview.

“Further, it seems that patients above 79 years of age or with elevated hemoglobin A1c levels, along with new users of NSAIDs, are particularly susceptible.” He added that no such association was found in patients below age 65 years with normal A1c levels.

Dr. Holt has a dual appointment as a cardiologist at Copenhagen University and Herlev-Gentofte Hospital in Hellerup, Denmark, and the department of epidemiology and biostatistics at the University of Auckland (New Zealand). Jarl Emmanuel Strange, MD, PhD, a fellow at Copenhagen University, is to present the abstract on Aug. 26.

“This is quite an important observation given that, unfortunately, NSAIDs continue to be prescribed rather easily to people with diabetes and these agents do have risk,” said Rodica Busui, MD, PhD, codirector of the JDRF Center of Excellence at the University of Michigan, Ann Arbor, and president-elect for medicine and science of the American Diabetes Association. Dr. Busui is also lead author of an ADA/American College of Cardiology consensus report on heart failure in diabetes.

The study hypothesized that fluid retention “is a known but underappreciated side effect” of NSAID use and that short-term NSAID use could lead to heart failure in patients with type 2 diabetes, which has been linked to subclinical cardiomyopathy and kidney dysfunction.

“According to this study and particularly the subgroups analyses, it seems that incident heart failure associated with short-term NSAID use could be more than ‘just fluid overload,’ ” Dr. Holt said. “Further investigations into the specific mechanisms causing these associations are warranted.”

The study identified 331,189 patients with type 2 diabetes in nationwide Danish registries from 1998 to 2018. Median age was 62 years, and 23,308 (7%) were hospitalized with heart failure during follow-up, Dr. Holt said. Of them, 16% claimed at least one NSAID prescription within 2 years and 3% claimed they had at least three prescriptions.

Study follow-up started 120 days after the first-time type 2 diabetes diagnosis and focused on patients who had no previous diagnosis of heart failure or rheumatologic disease. The investigators reported on patients who had one, two, three or four prescriptions for NSAID within a year of starting follow-up.

The study used a case-crossover design, which, the abstract stated, “uses each individual as his or her own control making it suitable to study the effect of short-term exposure on immediate events while mitigating unmeasured confounding.”

Dr. Holt noted that short-term NSAID use was linked to increased risk of heart failure hospitalization (odds ratio, 1.43; 95% confidence interval, 1.27-1.63). The investigators identified even greater risks in three subgroups: age of at least 80 years (OR, 1.78; 95% CI, 1.39-2.28), elevated A1c levels treated with one or less antidiabetic medication (OR 1.68; 95% CI, 1-2.88), and patients without previous NSAID use (OR, 2.71; 95% CI, 1.78-4.23).

In the cohort, celecoxib and naproxen were rarely used (0.4 and 0.9%, respectively), while 3.3% of patients took diclofenac or 12.2% ibuprofen. The latter two NSAIDs had ORs of 1.48 and 1.46, respectively, for hospitalization for new-onset heart failure using 28-day exposure windows (95% CI for both, 1.1­-2 and 1.26-1.69). No increased risk emerged for celecoxib or naproxen.

“High age and A1c levels and being a new user were tied to the strongest associations, along with known use of RASi [renin-angiotensin system inhibitors] and diuretics,” Dr. Holt said. “On the contrary, it seemed safe – from our data – to prescribe short-term NSAIDs for patients below 65 years of age and patients with normal A1c levels.

“Interestingly,” he added, “subclinical structural heart disease among patients with type 2 diabetes could play an important role.”

The findings are noteworthy, Dr. Busui said. “Although there are some limitations with the study design in general when one looks at data extracted from registers, the very large sample size and the fact that the Danish national register captures data in a standardized fashion does make the findings very relevant, especially now that we have confirmed that heart failure is the most prevalent cardiovascular complication in people with diabetes, as we have highlighted in the most recent ADA/ACC consensus on heart failure in diabetes.”

The study received funding from the Danish Heart Foundation and a number of private foundations. Dr. Holt and colleagues have no disclosures. Dr. Busui disclosed relationships with AstraZeneca, Boehringer Ingelheim–Lilly Alliance, Novo Nordisk, Averitas Pharma, Nevro, Regenacy Pharmaceuticals and Roche Diagnostics.

 

People with diabetes who take nonsteroidal anti-inflammatory drugs even on a short-term basis may have about a 50% greater risk of developing heart failure, according to results from a national registry study of more than 330,000 patients to be presented at the annual congress of the European Society of Cardiology.

“According to data from this study, even short-term NSAID use – within 28 days – in patients with type 2 diabetes mellitus are associated with an increased risk of first-time heart failure hospitalization,” lead author Anders Holt, MD, said in an interview.

“Further, it seems that patients above 79 years of age or with elevated hemoglobin A1c levels, along with new users of NSAIDs, are particularly susceptible.” He added that no such association was found in patients below age 65 years with normal A1c levels.

Dr. Holt has a dual appointment as a cardiologist at Copenhagen University and Herlev-Gentofte Hospital in Hellerup, Denmark, and the department of epidemiology and biostatistics at the University of Auckland (New Zealand). Jarl Emmanuel Strange, MD, PhD, a fellow at Copenhagen University, is to present the abstract on Aug. 26.

“This is quite an important observation given that, unfortunately, NSAIDs continue to be prescribed rather easily to people with diabetes and these agents do have risk,” said Rodica Busui, MD, PhD, codirector of the JDRF Center of Excellence at the University of Michigan, Ann Arbor, and president-elect for medicine and science of the American Diabetes Association. Dr. Busui is also lead author of an ADA/American College of Cardiology consensus report on heart failure in diabetes.

The study hypothesized that fluid retention “is a known but underappreciated side effect” of NSAID use and that short-term NSAID use could lead to heart failure in patients with type 2 diabetes, which has been linked to subclinical cardiomyopathy and kidney dysfunction.

“According to this study and particularly the subgroups analyses, it seems that incident heart failure associated with short-term NSAID use could be more than ‘just fluid overload,’ ” Dr. Holt said. “Further investigations into the specific mechanisms causing these associations are warranted.”

The study identified 331,189 patients with type 2 diabetes in nationwide Danish registries from 1998 to 2018. Median age was 62 years, and 23,308 (7%) were hospitalized with heart failure during follow-up, Dr. Holt said. Of them, 16% claimed at least one NSAID prescription within 2 years and 3% claimed they had at least three prescriptions.

Study follow-up started 120 days after the first-time type 2 diabetes diagnosis and focused on patients who had no previous diagnosis of heart failure or rheumatologic disease. The investigators reported on patients who had one, two, three or four prescriptions for NSAID within a year of starting follow-up.

The study used a case-crossover design, which, the abstract stated, “uses each individual as his or her own control making it suitable to study the effect of short-term exposure on immediate events while mitigating unmeasured confounding.”

Dr. Holt noted that short-term NSAID use was linked to increased risk of heart failure hospitalization (odds ratio, 1.43; 95% confidence interval, 1.27-1.63). The investigators identified even greater risks in three subgroups: age of at least 80 years (OR, 1.78; 95% CI, 1.39-2.28), elevated A1c levels treated with one or less antidiabetic medication (OR 1.68; 95% CI, 1-2.88), and patients without previous NSAID use (OR, 2.71; 95% CI, 1.78-4.23).

In the cohort, celecoxib and naproxen were rarely used (0.4 and 0.9%, respectively), while 3.3% of patients took diclofenac or 12.2% ibuprofen. The latter two NSAIDs had ORs of 1.48 and 1.46, respectively, for hospitalization for new-onset heart failure using 28-day exposure windows (95% CI for both, 1.1­-2 and 1.26-1.69). No increased risk emerged for celecoxib or naproxen.

“High age and A1c levels and being a new user were tied to the strongest associations, along with known use of RASi [renin-angiotensin system inhibitors] and diuretics,” Dr. Holt said. “On the contrary, it seemed safe – from our data – to prescribe short-term NSAIDs for patients below 65 years of age and patients with normal A1c levels.

“Interestingly,” he added, “subclinical structural heart disease among patients with type 2 diabetes could play an important role.”

The findings are noteworthy, Dr. Busui said. “Although there are some limitations with the study design in general when one looks at data extracted from registers, the very large sample size and the fact that the Danish national register captures data in a standardized fashion does make the findings very relevant, especially now that we have confirmed that heart failure is the most prevalent cardiovascular complication in people with diabetes, as we have highlighted in the most recent ADA/ACC consensus on heart failure in diabetes.”

The study received funding from the Danish Heart Foundation and a number of private foundations. Dr. Holt and colleagues have no disclosures. Dr. Busui disclosed relationships with AstraZeneca, Boehringer Ingelheim–Lilly Alliance, Novo Nordisk, Averitas Pharma, Nevro, Regenacy Pharmaceuticals and Roche Diagnostics.

 

People with diabetes who take nonsteroidal anti-inflammatory drugs even on a short-term basis may have about a 50% greater risk of developing heart failure, according to results from a national registry study of more than 330,000 patients to be presented at the annual congress of the European Society of Cardiology.

“According to data from this study, even short-term NSAID use – within 28 days – in patients with type 2 diabetes mellitus are associated with an increased risk of first-time heart failure hospitalization,” lead author Anders Holt, MD, said in an interview.

“Further, it seems that patients above 79 years of age or with elevated hemoglobin A1c levels, along with new users of NSAIDs, are particularly susceptible.” He added that no such association was found in patients below age 65 years with normal A1c levels.

Dr. Holt has a dual appointment as a cardiologist at Copenhagen University and Herlev-Gentofte Hospital in Hellerup, Denmark, and the department of epidemiology and biostatistics at the University of Auckland (New Zealand). Jarl Emmanuel Strange, MD, PhD, a fellow at Copenhagen University, is to present the abstract on Aug. 26.

“This is quite an important observation given that, unfortunately, NSAIDs continue to be prescribed rather easily to people with diabetes and these agents do have risk,” said Rodica Busui, MD, PhD, codirector of the JDRF Center of Excellence at the University of Michigan, Ann Arbor, and president-elect for medicine and science of the American Diabetes Association. Dr. Busui is also lead author of an ADA/American College of Cardiology consensus report on heart failure in diabetes.

The study hypothesized that fluid retention “is a known but underappreciated side effect” of NSAID use and that short-term NSAID use could lead to heart failure in patients with type 2 diabetes, which has been linked to subclinical cardiomyopathy and kidney dysfunction.

“According to this study and particularly the subgroups analyses, it seems that incident heart failure associated with short-term NSAID use could be more than ‘just fluid overload,’ ” Dr. Holt said. “Further investigations into the specific mechanisms causing these associations are warranted.”

The study identified 331,189 patients with type 2 diabetes in nationwide Danish registries from 1998 to 2018. Median age was 62 years, and 23,308 (7%) were hospitalized with heart failure during follow-up, Dr. Holt said. Of them, 16% claimed at least one NSAID prescription within 2 years and 3% claimed they had at least three prescriptions.

Study follow-up started 120 days after the first-time type 2 diabetes diagnosis and focused on patients who had no previous diagnosis of heart failure or rheumatologic disease. The investigators reported on patients who had one, two, three or four prescriptions for NSAID within a year of starting follow-up.

The study used a case-crossover design, which, the abstract stated, “uses each individual as his or her own control making it suitable to study the effect of short-term exposure on immediate events while mitigating unmeasured confounding.”

Dr. Holt noted that short-term NSAID use was linked to increased risk of heart failure hospitalization (odds ratio, 1.43; 95% confidence interval, 1.27-1.63). The investigators identified even greater risks in three subgroups: age of at least 80 years (OR, 1.78; 95% CI, 1.39-2.28), elevated A1c levels treated with one or less antidiabetic medication (OR 1.68; 95% CI, 1-2.88), and patients without previous NSAID use (OR, 2.71; 95% CI, 1.78-4.23).

In the cohort, celecoxib and naproxen were rarely used (0.4 and 0.9%, respectively), while 3.3% of patients took diclofenac or 12.2% ibuprofen. The latter two NSAIDs had ORs of 1.48 and 1.46, respectively, for hospitalization for new-onset heart failure using 28-day exposure windows (95% CI for both, 1.1­-2 and 1.26-1.69). No increased risk emerged for celecoxib or naproxen.

“High age and A1c levels and being a new user were tied to the strongest associations, along with known use of RASi [renin-angiotensin system inhibitors] and diuretics,” Dr. Holt said. “On the contrary, it seemed safe – from our data – to prescribe short-term NSAIDs for patients below 65 years of age and patients with normal A1c levels.

“Interestingly,” he added, “subclinical structural heart disease among patients with type 2 diabetes could play an important role.”

The findings are noteworthy, Dr. Busui said. “Although there are some limitations with the study design in general when one looks at data extracted from registers, the very large sample size and the fact that the Danish national register captures data in a standardized fashion does make the findings very relevant, especially now that we have confirmed that heart failure is the most prevalent cardiovascular complication in people with diabetes, as we have highlighted in the most recent ADA/ACC consensus on heart failure in diabetes.”

The study received funding from the Danish Heart Foundation and a number of private foundations. Dr. Holt and colleagues have no disclosures. Dr. Busui disclosed relationships with AstraZeneca, Boehringer Ingelheim–Lilly Alliance, Novo Nordisk, Averitas Pharma, Nevro, Regenacy Pharmaceuticals and Roche Diagnostics.

 

Elderly patients with atrial fibrillation (AF) who are at high risk of bleeding may benefit from a low 15-mg dose of edoxaban, regardless of their frailty status, a subanalysis of the ELDERCARE-AF trial suggests.  

Major bleeding and major or clinically relevant nonmajor bleeding events were both numerically higher in the edoxaban group than placebo, the authors reported, with no heterogeneity by frailty status.

The subanalysis extends findings of the overall study by teasing out stroke, systemic embolism (SSE) and bleeding events across frailty status among Japanese patients aged 80 and older who were ineligible for oral anticoagulants (OACs) at usual doses.

Findings from the original phase 3 ELDERCARE-AF study were previously reported during the virtual European Society of Cardiology Congress 2020 and simultaneously published in The New England Journal of Medicine. The current study was published online in JAMA Network Open.
 

All frailty levels benefited

Shintaro Akashi, MD, PhD, of National Hospital Organization Hamada Medical Center, Shimane, Japan, and colleagues analyzed data from 944 patients randomly assigned to edoxaban 15 mg or placebo for about 3 years. The mean age of participants was 86.6 years and 57% were women. Baseline characteristics, including history of bleeding, were similar between groups.

Patient physical condition was assessed via five parameters: weight loss, grip strength, walking speed, exhaustion, and activity level. This yielded a frailty score, with one point given for each parameter: 0 indicated robust; 1 or 2, prefrail; and 3 or higher, frail. For this analysis, robust (6.5% of patients) and prefrail (51%) were combined and categorized as nonfrail.

In the placebo group, estimated event rates for stroke or SSE were 7.1% per patient-year among frail patients and 6.1% per patient-year among those who were nonfrail.

In the edoxaban group, SSE occurred at an estimated event rate of 2.5% of frail patients and 1.5% of nonfrail patients (adjusted HR, 1.41).

The edoxaban group “consistently had fewer SSE events regardless of frailty status including each frailty assessment parameter, and there was no heterogeneity between the groups,” the authors wrote, with similar trends for the association of edoxaban 15 mg for each frailty assessment parameter.

However, major bleeding and major or clinically relevant nonmajor (CRNM) bleeding events were both higher with edoxaban, regardless of frailty status.

More specifically, in the placebo group, the incidence of major bleeding was 2.3% in the frail group and 1.5% in the nonfrail group (adjusted HR, 1.48) versus 3.7% and 2.9%, respectively, in the edoxaban group (adjusted HR, 1.04).

In addition, exhaustion was related to a significantly increased risk of major or CRNM bleeding in frail versus nonfrail patients (16.3% vs. 8.4%; adjusted HR, 1.97). The incidences were all higher in the edoxaban group, irrespective of frailty status.

Furthermore, although both all-cause death and the net clinical composite outcome of stroke or SSE occurred more frequently in frail than in nonfrail patients, there was no association with frailty status between the edoxaban and placebo groups.

Findings unrelated to edoxaban were also noteworthy. “Surprisingly, grip strength showed an association with adverse events,” the authors wrote. Among those with lower grip strength, “there was nearly a 3-fold increase in risk of SSE and major bleeding and a more than 16-fold significant increase in risk of death. In addition, in those with exhaustion, there was nearly a 2-fold significant increase in major or CRNM bleeding.”

Thus, they suggested, in this patient population, “an objective physical assessment of grip strength or exhaustion in addition to the well-known walking speed may more accurately estimate the risks of clinical outcomes than the overall frailty assessment.”

Head-to-head comparisons needed

Commenting on the findings, Richard Kovach, MD, chair of the interventional cardiology division at Deborah Heart and Lung Center, Browns Mills, N.J., said, “It is interesting that the lower dose of edoxaban still appears to have a statistically significant reduction in the incidence of stroke in this subgroup of extremely frail elderly patients, and it may be useful in this highly selected subset.

“That being said,” he added, “the major complication of oral anticoagulants – major bleeding – appears to be similar to other NOACs prescribed more frequently in the U.S., specifically rivaroxaban and apixaban.”

“Furthermore, in the U.S., frail or complex patients who are not candidates for oral anticoagulant therapy are much more likely to receive a left atrial appendage closure device such as a Watchman or Amulet in order to avoid the risk of bleeding complications completely,” he said. “Procedural success with these devices is extremely high and procedural complications are extremely low. With both devices, the long-term reduction in stroke risk is equivalent to the use of anticoagulant therapy.

“Clearly, more research is needed to compare the outcomes with edoxaban against other NOACs,” Dr. Kovach concluded. “A head-to-head comparison of low-dose edoxaban versus left atrial appendage closure in this high-risk group would also be of great clinical value.”

The study was funded by Daiichi Sankyo. Two coauthors are employees of and five have received fees from the company. Dr. Kovach has reported no relevant financial relationships.

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

Elderly patients with atrial fibrillation (AF) who are at high risk of bleeding may benefit from a low 15-mg dose of edoxaban, regardless of their frailty status, a subanalysis of the ELDERCARE-AF trial suggests.  

Major bleeding and major or clinically relevant nonmajor bleeding events were both numerically higher in the edoxaban group than placebo, the authors reported, with no heterogeneity by frailty status.

The subanalysis extends findings of the overall study by teasing out stroke, systemic embolism (SSE) and bleeding events across frailty status among Japanese patients aged 80 and older who were ineligible for oral anticoagulants (OACs) at usual doses.

Findings from the original phase 3 ELDERCARE-AF study were previously reported during the virtual European Society of Cardiology Congress 2020 and simultaneously published in The New England Journal of Medicine. The current study was published online in JAMA Network Open.
 

All frailty levels benefited

Shintaro Akashi, MD, PhD, of National Hospital Organization Hamada Medical Center, Shimane, Japan, and colleagues analyzed data from 944 patients randomly assigned to edoxaban 15 mg or placebo for about 3 years. The mean age of participants was 86.6 years and 57% were women. Baseline characteristics, including history of bleeding, were similar between groups.

Patient physical condition was assessed via five parameters: weight loss, grip strength, walking speed, exhaustion, and activity level. This yielded a frailty score, with one point given for each parameter: 0 indicated robust; 1 or 2, prefrail; and 3 or higher, frail. For this analysis, robust (6.5% of patients) and prefrail (51%) were combined and categorized as nonfrail.

In the placebo group, estimated event rates for stroke or SSE were 7.1% per patient-year among frail patients and 6.1% per patient-year among those who were nonfrail.

In the edoxaban group, SSE occurred at an estimated event rate of 2.5% of frail patients and 1.5% of nonfrail patients (adjusted HR, 1.41).

The edoxaban group “consistently had fewer SSE events regardless of frailty status including each frailty assessment parameter, and there was no heterogeneity between the groups,” the authors wrote, with similar trends for the association of edoxaban 15 mg for each frailty assessment parameter.

However, major bleeding and major or clinically relevant nonmajor (CRNM) bleeding events were both higher with edoxaban, regardless of frailty status.

More specifically, in the placebo group, the incidence of major bleeding was 2.3% in the frail group and 1.5% in the nonfrail group (adjusted HR, 1.48) versus 3.7% and 2.9%, respectively, in the edoxaban group (adjusted HR, 1.04).

In addition, exhaustion was related to a significantly increased risk of major or CRNM bleeding in frail versus nonfrail patients (16.3% vs. 8.4%; adjusted HR, 1.97). The incidences were all higher in the edoxaban group, irrespective of frailty status.

Furthermore, although both all-cause death and the net clinical composite outcome of stroke or SSE occurred more frequently in frail than in nonfrail patients, there was no association with frailty status between the edoxaban and placebo groups.

Findings unrelated to edoxaban were also noteworthy. “Surprisingly, grip strength showed an association with adverse events,” the authors wrote. Among those with lower grip strength, “there was nearly a 3-fold increase in risk of SSE and major bleeding and a more than 16-fold significant increase in risk of death. In addition, in those with exhaustion, there was nearly a 2-fold significant increase in major or CRNM bleeding.”

Thus, they suggested, in this patient population, “an objective physical assessment of grip strength or exhaustion in addition to the well-known walking speed may more accurately estimate the risks of clinical outcomes than the overall frailty assessment.”

Head-to-head comparisons needed

Commenting on the findings, Richard Kovach, MD, chair of the interventional cardiology division at Deborah Heart and Lung Center, Browns Mills, N.J., said, “It is interesting that the lower dose of edoxaban still appears to have a statistically significant reduction in the incidence of stroke in this subgroup of extremely frail elderly patients, and it may be useful in this highly selected subset.

“That being said,” he added, “the major complication of oral anticoagulants – major bleeding – appears to be similar to other NOACs prescribed more frequently in the U.S., specifically rivaroxaban and apixaban.”

“Furthermore, in the U.S., frail or complex patients who are not candidates for oral anticoagulant therapy are much more likely to receive a left atrial appendage closure device such as a Watchman or Amulet in order to avoid the risk of bleeding complications completely,” he said. “Procedural success with these devices is extremely high and procedural complications are extremely low. With both devices, the long-term reduction in stroke risk is equivalent to the use of anticoagulant therapy.

“Clearly, more research is needed to compare the outcomes with edoxaban against other NOACs,” Dr. Kovach concluded. “A head-to-head comparison of low-dose edoxaban versus left atrial appendage closure in this high-risk group would also be of great clinical value.”

The study was funded by Daiichi Sankyo. Two coauthors are employees of and five have received fees from the company. Dr. Kovach has reported no relevant financial relationships.

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

Elderly patients with atrial fibrillation (AF) who are at high risk of bleeding may benefit from a low 15-mg dose of edoxaban, regardless of their frailty status, a subanalysis of the ELDERCARE-AF trial suggests.  

Major bleeding and major or clinically relevant nonmajor bleeding events were both numerically higher in the edoxaban group than placebo, the authors reported, with no heterogeneity by frailty status.

The subanalysis extends findings of the overall study by teasing out stroke, systemic embolism (SSE) and bleeding events across frailty status among Japanese patients aged 80 and older who were ineligible for oral anticoagulants (OACs) at usual doses.

Findings from the original phase 3 ELDERCARE-AF study were previously reported during the virtual European Society of Cardiology Congress 2020 and simultaneously published in The New England Journal of Medicine. The current study was published online in JAMA Network Open.
 

All frailty levels benefited

Shintaro Akashi, MD, PhD, of National Hospital Organization Hamada Medical Center, Shimane, Japan, and colleagues analyzed data from 944 patients randomly assigned to edoxaban 15 mg or placebo for about 3 years. The mean age of participants was 86.6 years and 57% were women. Baseline characteristics, including history of bleeding, were similar between groups.

Patient physical condition was assessed via five parameters: weight loss, grip strength, walking speed, exhaustion, and activity level. This yielded a frailty score, with one point given for each parameter: 0 indicated robust; 1 or 2, prefrail; and 3 or higher, frail. For this analysis, robust (6.5% of patients) and prefrail (51%) were combined and categorized as nonfrail.

In the placebo group, estimated event rates for stroke or SSE were 7.1% per patient-year among frail patients and 6.1% per patient-year among those who were nonfrail.

In the edoxaban group, SSE occurred at an estimated event rate of 2.5% of frail patients and 1.5% of nonfrail patients (adjusted HR, 1.41).

The edoxaban group “consistently had fewer SSE events regardless of frailty status including each frailty assessment parameter, and there was no heterogeneity between the groups,” the authors wrote, with similar trends for the association of edoxaban 15 mg for each frailty assessment parameter.

However, major bleeding and major or clinically relevant nonmajor (CRNM) bleeding events were both higher with edoxaban, regardless of frailty status.

More specifically, in the placebo group, the incidence of major bleeding was 2.3% in the frail group and 1.5% in the nonfrail group (adjusted HR, 1.48) versus 3.7% and 2.9%, respectively, in the edoxaban group (adjusted HR, 1.04).

In addition, exhaustion was related to a significantly increased risk of major or CRNM bleeding in frail versus nonfrail patients (16.3% vs. 8.4%; adjusted HR, 1.97). The incidences were all higher in the edoxaban group, irrespective of frailty status.

Furthermore, although both all-cause death and the net clinical composite outcome of stroke or SSE occurred more frequently in frail than in nonfrail patients, there was no association with frailty status between the edoxaban and placebo groups.

Findings unrelated to edoxaban were also noteworthy. “Surprisingly, grip strength showed an association with adverse events,” the authors wrote. Among those with lower grip strength, “there was nearly a 3-fold increase in risk of SSE and major bleeding and a more than 16-fold significant increase in risk of death. In addition, in those with exhaustion, there was nearly a 2-fold significant increase in major or CRNM bleeding.”

Thus, they suggested, in this patient population, “an objective physical assessment of grip strength or exhaustion in addition to the well-known walking speed may more accurately estimate the risks of clinical outcomes than the overall frailty assessment.”

Head-to-head comparisons needed

Commenting on the findings, Richard Kovach, MD, chair of the interventional cardiology division at Deborah Heart and Lung Center, Browns Mills, N.J., said, “It is interesting that the lower dose of edoxaban still appears to have a statistically significant reduction in the incidence of stroke in this subgroup of extremely frail elderly patients, and it may be useful in this highly selected subset.

“That being said,” he added, “the major complication of oral anticoagulants – major bleeding – appears to be similar to other NOACs prescribed more frequently in the U.S., specifically rivaroxaban and apixaban.”

“Furthermore, in the U.S., frail or complex patients who are not candidates for oral anticoagulant therapy are much more likely to receive a left atrial appendage closure device such as a Watchman or Amulet in order to avoid the risk of bleeding complications completely,” he said. “Procedural success with these devices is extremely high and procedural complications are extremely low. With both devices, the long-term reduction in stroke risk is equivalent to the use of anticoagulant therapy.

“Clearly, more research is needed to compare the outcomes with edoxaban against other NOACs,” Dr. Kovach concluded. “A head-to-head comparison of low-dose edoxaban versus left atrial appendage closure in this high-risk group would also be of great clinical value.”

The study was funded by Daiichi Sankyo. Two coauthors are employees of and five have received fees from the company. Dr. Kovach has reported no relevant financial relationships.

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

After 2 years of virtual gatherings, the annual European Society of Cardiology Congress 2022 is back and celebrating its 70th birthday live in the raucously beautiful city of Barcelona.

Much of the upcoming event, scheduled for Aug. 26 to 29, however, will also be broadcast online, and the full program will be available on-demand after the meeting.

The hybrid format is intentional, leveraging the social interaction that only live meetings can provide and the global reach of online access, Program Committee Chair Stephan Windecker, MD, Bern University Hospital, Switzerland, told this news organization.

“It enables a lot of people who, for some reason, cannot travel to still connect, and it also provides what we’ve done in the past, but I think in a more natural way of doing it,” he said. “You can connect later on again, read, digest, look at sessions that you may have missed, and that’s a nice experience to take advantage of.”

Thus far, early registrations are favoring the sunny climes, with about 14,000 onsite and 4,200 online attendees.

This year’s spotlight theme is cardiac imaging, with programming throughout the Congress devoted to its role in diagnosis, treatment, follow-up, and, increasingly, guidance of interventions.

“Particularly as it relates to the transcatheter heart valves, it’s really a new discipline, and I think you can’t overemphasize that enough, because the interventional result directly depends on the quality of imaging,” Dr. Windecker said. “This will certainly logarithmically increase during the next few years.”

The always highly anticipated Hot Line sessions mushroomed this year to 10, featuring 36 studies, up from just 4 sessions and 20 studies last year.

“Especially during the COVID pandemic, many investigators and trialists experienced difficulties in recruitment, difficulties in terms of also personnel shortages, and so on. So really, we feel very privileged at the large number of submissions,” he said. “I think there are really very interesting ones, which we tried to spread throughout the 4 days.”
 

Hot Line sessions 1-5

Among the studies Dr. Windecker highlighted is TIME, which kicks off Hot Line 1 on Friday, Aug. 26, and aimed to establish whether antihypertensive medications taken at night are truly more cardioprotective than those taken in the morning.

The topic has been hotly debated, with proponents pointing to a near halving of mortality and cardiovascular events with bedtime dosing in the Hygia Chronotherapy trial. Skeptics question the validity and conduct of the trial, however, prompting an investigation by the European Heart Journal, which found no evidence of misconduct but has many looking for more definitive data.

Also in this session is SECURE, pitting a cardiovascular polypill that contains aspirin, ramipril, and atorvastatin against usual care in secondary prevention, and PERSPECTIVE, comparing the effects of sacubitril/valsartan with valsartan on cognitive function in patients with chronic heart failure and preserved ejection fraction (HFpEF).

Hot Line 2, the first of three Hot Lines taking place on Saturday, Aug. 27, features the Danish cardiovascular screening trial DANCAVAS, the phase 4 ADVOR trial of acetazolamide (Diamox) in acute decompensated heart failure (HF), and the DANFLU-1 trial of high- versus standard-dose influenza vaccine in the elderly.

Also on tap is the BOX trial, comparing two blood pressure and two oxygenation targets in comatose out-of-hospital cardiac arrest patients.

“It addresses an understudied patient population, and the second element is that sometimes things you do out of ordinary application – so, the application of oxygen – may have beneficial but also adverse impact,” Dr. Windecker said. “So, to study this in a randomized clinical trial is really important.”

Additionally, he highlighted REVIVED, which will be presented in Hot Line 3 and is the first trial to examine percutaneous coronary intervention (PCI) with optimal medical therapy (OMT) versus OMT alone in the setting of severe ischemic cardiomyopathy.

“We have data from the STICH trial, where surgical revascularization was investigated in ischemic cardiomyopathy, but the open question is: What about PCI as revascularization?” Dr. Windecker said. “The other reason it’s interesting is that we have these evidence-based drugs that have dramatically improved outcomes in patients with heart failure, and REVIVED certainly has been conducted now in an era where at least some of these drugs are more systematically implemented.”

Rounding out this session are the Scottish ALL-HEART study of allopurinol in ischemic heart disease and EchoNet-RCT, looking at whether artificial intelligence (AI) can improve the accuracy of echocardiograms.

Hot Line 4 features DELIVER, a phase 3 trial of the SGLT2 inhibitor dapagliflozin (Farxiga) in HF with preserved or mildly reduced ejection fraction. Topline results, released in May, showed that the study has met its primary endpoint of cardiovascular death or worsening HF.

Dr. Windecker said DELIVER will be a “highlight” of the meeting, particularly because EMPEROR-Preserved, presented at ESC 2021, showed a benefit for another SGLT2 inhibitor, empagliflozin, in this very specific setting. Two prespecified analyses will also be presented, pooling data from EMPEROR-Preserved and from the DAPA-HF study of dapagliflozin in patients with reduced EF. “This will be a session very rich in terms of information.”

Another not-to-be-missed session is Hot Line 5, which will focus on antithrombotic therapy, according to Dr. Windecker, who will cochair the Sunday, Aug. 28 session.

First up is the investigator-initiated INVICTUS-VKA, testing rivaroxaban noninferiority versus standard vitamin K antagonists in patients with atrial fibrillation (AFib) and rheumatic heart disease, a setting in which non–vitamin K antagonists have not been sufficiently tested.

This is followed by three phase 2 trials – PACIFIC-AMI, PACIFIC-STROKE, and AXIOMATIC-SSP – investigating the novel factor XIa inhibitors BAY 2433334 and BMS-986177 in patients with myocardial infarction or stroke.
 

Hot Line sessions 6-10

Sunday’s Hot Line 6 takes another look at smartphone-based AFib screening in eBRAVE-HF, use of causal AI to improve the validity of cardiovascular risk prediction, and AI-enhanced detection of aortic stenosis.

Hot Line 7 rounds out the day, putting coronary imaging center stage. It includes perfusion scanning with MR or PET after a positive angiogram in DanNICAD-2, the PET tracer 18F-sodium fluoride as a marker of high-risk coronary plaques in patients with recent MIs in PREFFIR, and fractional flow reserve- versus angiography-guided PCI in acute MI with multivessel disease in FRAME-AMI.

After a weekend of top-notch science and, no doubt, a spot of revelry, the focus returns on Monday, Aug. 29 to three Hot Line sessions. The first of these, Hot Line 8, updates five clinical trials, including 5-year outcomes from ISCHEMIA-CKD EXTEND, 15-month results from MASTER DAPT, and primary results from FOURIER-OLE, the open-label extension study of evolocumab out to 5 years in approximately 1,600 study participants.

The session closes out with causes of mortality in the FIDELITY trial of finerenone and a win-ratio analysis of PARADISE-MI.

Hot Line 9, billed as an “evidence synthesis on clinically important questions,” includes a Cholesterol Treatment Trialists’ (CTT) Collaboration meta-analysis on the effects of statins on muscle symptoms and a meta-analysis of angiotensin-receptor blockers and beta-blockers in Marfan syndrome from the Marfan Treatment Trialists’ Collaboration.

Also featured is evidence on radial versus femoral access for coronary procedures, and PANTHER, a patient-level meta-analysis of aspirin or P2Y12 inhibitor monotherapy as secondary prevention in patients with established coronary artery disease.

COVID-19, deeply rooted in the minds of attendees and considered in 52 separate sessions, takes over the final Hot Line session of the Congress. Hot Line 10 will report on antithrombotic therapy in critically ill patients in COVID-PACT and on anti-inflammatory therapy with colchicine and antithrombotic therapy with aspirin alone or in combination with rivaroxaban in the ACT inpatient and outpatient trials. Although such early trials have been largely negative, the latest details will be interesting to see, Dr. Windecker suggested.

In terms of COVID-19 protocols, ESC will recommend but not mandate masks and will have test kits available should attendees wish to have a test or if they become symptomatic, he noted.
 

New guidelines released

Four new ESC guidelines will be released during the congress on cardio-oncology, ventricular arrhythmias and sudden cardiac death, pulmonary hypertension, and cardiovascular assessment and management of patients undergoing noncardiac surgery.

In addition to a guideline overview on Friday, one guideline will be featured each day in a 1-hour session, with additional time for discussions with guideline task force members, and six sessions devoted to the implementation of existing guidelines in clinical practice.

The ESC already has a position paper on cardio-oncology, but now, for the first time, has a full guideline with formal laws and level-of-evidence recommendations, Dr. Windecker pointed out.

“I think what will be the great asset, not only of the guideline but out of this emerging field, is that people in the future will probably not only be treated when it’s too late or suffer from toxicity but that there will be screening, and people will be aware before the implementation of therapy,” he added.

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

After 2 years of virtual gatherings, the annual European Society of Cardiology Congress 2022 is back and celebrating its 70th birthday live in the raucously beautiful city of Barcelona.

Much of the upcoming event, scheduled for Aug. 26 to 29, however, will also be broadcast online, and the full program will be available on-demand after the meeting.

The hybrid format is intentional, leveraging the social interaction that only live meetings can provide and the global reach of online access, Program Committee Chair Stephan Windecker, MD, Bern University Hospital, Switzerland, told this news organization.

“It enables a lot of people who, for some reason, cannot travel to still connect, and it also provides what we’ve done in the past, but I think in a more natural way of doing it,” he said. “You can connect later on again, read, digest, look at sessions that you may have missed, and that’s a nice experience to take advantage of.”

Thus far, early registrations are favoring the sunny climes, with about 14,000 onsite and 4,200 online attendees.

This year’s spotlight theme is cardiac imaging, with programming throughout the Congress devoted to its role in diagnosis, treatment, follow-up, and, increasingly, guidance of interventions.

“Particularly as it relates to the transcatheter heart valves, it’s really a new discipline, and I think you can’t overemphasize that enough, because the interventional result directly depends on the quality of imaging,” Dr. Windecker said. “This will certainly logarithmically increase during the next few years.”

The always highly anticipated Hot Line sessions mushroomed this year to 10, featuring 36 studies, up from just 4 sessions and 20 studies last year.

“Especially during the COVID pandemic, many investigators and trialists experienced difficulties in recruitment, difficulties in terms of also personnel shortages, and so on. So really, we feel very privileged at the large number of submissions,” he said. “I think there are really very interesting ones, which we tried to spread throughout the 4 days.”
 

Hot Line sessions 1-5

Among the studies Dr. Windecker highlighted is TIME, which kicks off Hot Line 1 on Friday, Aug. 26, and aimed to establish whether antihypertensive medications taken at night are truly more cardioprotective than those taken in the morning.

The topic has been hotly debated, with proponents pointing to a near halving of mortality and cardiovascular events with bedtime dosing in the Hygia Chronotherapy trial. Skeptics question the validity and conduct of the trial, however, prompting an investigation by the European Heart Journal, which found no evidence of misconduct but has many looking for more definitive data.

Also in this session is SECURE, pitting a cardiovascular polypill that contains aspirin, ramipril, and atorvastatin against usual care in secondary prevention, and PERSPECTIVE, comparing the effects of sacubitril/valsartan with valsartan on cognitive function in patients with chronic heart failure and preserved ejection fraction (HFpEF).

Hot Line 2, the first of three Hot Lines taking place on Saturday, Aug. 27, features the Danish cardiovascular screening trial DANCAVAS, the phase 4 ADVOR trial of acetazolamide (Diamox) in acute decompensated heart failure (HF), and the DANFLU-1 trial of high- versus standard-dose influenza vaccine in the elderly.

Also on tap is the BOX trial, comparing two blood pressure and two oxygenation targets in comatose out-of-hospital cardiac arrest patients.

“It addresses an understudied patient population, and the second element is that sometimes things you do out of ordinary application – so, the application of oxygen – may have beneficial but also adverse impact,” Dr. Windecker said. “So, to study this in a randomized clinical trial is really important.”

Additionally, he highlighted REVIVED, which will be presented in Hot Line 3 and is the first trial to examine percutaneous coronary intervention (PCI) with optimal medical therapy (OMT) versus OMT alone in the setting of severe ischemic cardiomyopathy.

“We have data from the STICH trial, where surgical revascularization was investigated in ischemic cardiomyopathy, but the open question is: What about PCI as revascularization?” Dr. Windecker said. “The other reason it’s interesting is that we have these evidence-based drugs that have dramatically improved outcomes in patients with heart failure, and REVIVED certainly has been conducted now in an era where at least some of these drugs are more systematically implemented.”

Rounding out this session are the Scottish ALL-HEART study of allopurinol in ischemic heart disease and EchoNet-RCT, looking at whether artificial intelligence (AI) can improve the accuracy of echocardiograms.

Hot Line 4 features DELIVER, a phase 3 trial of the SGLT2 inhibitor dapagliflozin (Farxiga) in HF with preserved or mildly reduced ejection fraction. Topline results, released in May, showed that the study has met its primary endpoint of cardiovascular death or worsening HF.

Dr. Windecker said DELIVER will be a “highlight” of the meeting, particularly because EMPEROR-Preserved, presented at ESC 2021, showed a benefit for another SGLT2 inhibitor, empagliflozin, in this very specific setting. Two prespecified analyses will also be presented, pooling data from EMPEROR-Preserved and from the DAPA-HF study of dapagliflozin in patients with reduced EF. “This will be a session very rich in terms of information.”

Another not-to-be-missed session is Hot Line 5, which will focus on antithrombotic therapy, according to Dr. Windecker, who will cochair the Sunday, Aug. 28 session.

First up is the investigator-initiated INVICTUS-VKA, testing rivaroxaban noninferiority versus standard vitamin K antagonists in patients with atrial fibrillation (AFib) and rheumatic heart disease, a setting in which non–vitamin K antagonists have not been sufficiently tested.

This is followed by three phase 2 trials – PACIFIC-AMI, PACIFIC-STROKE, and AXIOMATIC-SSP – investigating the novel factor XIa inhibitors BAY 2433334 and BMS-986177 in patients with myocardial infarction or stroke.
 

Hot Line sessions 6-10

Sunday’s Hot Line 6 takes another look at smartphone-based AFib screening in eBRAVE-HF, use of causal AI to improve the validity of cardiovascular risk prediction, and AI-enhanced detection of aortic stenosis.

Hot Line 7 rounds out the day, putting coronary imaging center stage. It includes perfusion scanning with MR or PET after a positive angiogram in DanNICAD-2, the PET tracer 18F-sodium fluoride as a marker of high-risk coronary plaques in patients with recent MIs in PREFFIR, and fractional flow reserve- versus angiography-guided PCI in acute MI with multivessel disease in FRAME-AMI.

After a weekend of top-notch science and, no doubt, a spot of revelry, the focus returns on Monday, Aug. 29 to three Hot Line sessions. The first of these, Hot Line 8, updates five clinical trials, including 5-year outcomes from ISCHEMIA-CKD EXTEND, 15-month results from MASTER DAPT, and primary results from FOURIER-OLE, the open-label extension study of evolocumab out to 5 years in approximately 1,600 study participants.

The session closes out with causes of mortality in the FIDELITY trial of finerenone and a win-ratio analysis of PARADISE-MI.

Hot Line 9, billed as an “evidence synthesis on clinically important questions,” includes a Cholesterol Treatment Trialists’ (CTT) Collaboration meta-analysis on the effects of statins on muscle symptoms and a meta-analysis of angiotensin-receptor blockers and beta-blockers in Marfan syndrome from the Marfan Treatment Trialists’ Collaboration.

Also featured is evidence on radial versus femoral access for coronary procedures, and PANTHER, a patient-level meta-analysis of aspirin or P2Y12 inhibitor monotherapy as secondary prevention in patients with established coronary artery disease.

COVID-19, deeply rooted in the minds of attendees and considered in 52 separate sessions, takes over the final Hot Line session of the Congress. Hot Line 10 will report on antithrombotic therapy in critically ill patients in COVID-PACT and on anti-inflammatory therapy with colchicine and antithrombotic therapy with aspirin alone or in combination with rivaroxaban in the ACT inpatient and outpatient trials. Although such early trials have been largely negative, the latest details will be interesting to see, Dr. Windecker suggested.

In terms of COVID-19 protocols, ESC will recommend but not mandate masks and will have test kits available should attendees wish to have a test or if they become symptomatic, he noted.
 

New guidelines released

Four new ESC guidelines will be released during the congress on cardio-oncology, ventricular arrhythmias and sudden cardiac death, pulmonary hypertension, and cardiovascular assessment and management of patients undergoing noncardiac surgery.

In addition to a guideline overview on Friday, one guideline will be featured each day in a 1-hour session, with additional time for discussions with guideline task force members, and six sessions devoted to the implementation of existing guidelines in clinical practice.

The ESC already has a position paper on cardio-oncology, but now, for the first time, has a full guideline with formal laws and level-of-evidence recommendations, Dr. Windecker pointed out.

“I think what will be the great asset, not only of the guideline but out of this emerging field, is that people in the future will probably not only be treated when it’s too late or suffer from toxicity but that there will be screening, and people will be aware before the implementation of therapy,” he added.

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

After 2 years of virtual gatherings, the annual European Society of Cardiology Congress 2022 is back and celebrating its 70th birthday live in the raucously beautiful city of Barcelona.

Much of the upcoming event, scheduled for Aug. 26 to 29, however, will also be broadcast online, and the full program will be available on-demand after the meeting.

The hybrid format is intentional, leveraging the social interaction that only live meetings can provide and the global reach of online access, Program Committee Chair Stephan Windecker, MD, Bern University Hospital, Switzerland, told this news organization.

“It enables a lot of people who, for some reason, cannot travel to still connect, and it also provides what we’ve done in the past, but I think in a more natural way of doing it,” he said. “You can connect later on again, read, digest, look at sessions that you may have missed, and that’s a nice experience to take advantage of.”

Thus far, early registrations are favoring the sunny climes, with about 14,000 onsite and 4,200 online attendees.

This year’s spotlight theme is cardiac imaging, with programming throughout the Congress devoted to its role in diagnosis, treatment, follow-up, and, increasingly, guidance of interventions.

“Particularly as it relates to the transcatheter heart valves, it’s really a new discipline, and I think you can’t overemphasize that enough, because the interventional result directly depends on the quality of imaging,” Dr. Windecker said. “This will certainly logarithmically increase during the next few years.”

The always highly anticipated Hot Line sessions mushroomed this year to 10, featuring 36 studies, up from just 4 sessions and 20 studies last year.

“Especially during the COVID pandemic, many investigators and trialists experienced difficulties in recruitment, difficulties in terms of also personnel shortages, and so on. So really, we feel very privileged at the large number of submissions,” he said. “I think there are really very interesting ones, which we tried to spread throughout the 4 days.”
 

Hot Line sessions 1-5

Among the studies Dr. Windecker highlighted is TIME, which kicks off Hot Line 1 on Friday, Aug. 26, and aimed to establish whether antihypertensive medications taken at night are truly more cardioprotective than those taken in the morning.

The topic has been hotly debated, with proponents pointing to a near halving of mortality and cardiovascular events with bedtime dosing in the Hygia Chronotherapy trial. Skeptics question the validity and conduct of the trial, however, prompting an investigation by the European Heart Journal, which found no evidence of misconduct but has many looking for more definitive data.

Also in this session is SECURE, pitting a cardiovascular polypill that contains aspirin, ramipril, and atorvastatin against usual care in secondary prevention, and PERSPECTIVE, comparing the effects of sacubitril/valsartan with valsartan on cognitive function in patients with chronic heart failure and preserved ejection fraction (HFpEF).

Hot Line 2, the first of three Hot Lines taking place on Saturday, Aug. 27, features the Danish cardiovascular screening trial DANCAVAS, the phase 4 ADVOR trial of acetazolamide (Diamox) in acute decompensated heart failure (HF), and the DANFLU-1 trial of high- versus standard-dose influenza vaccine in the elderly.

Also on tap is the BOX trial, comparing two blood pressure and two oxygenation targets in comatose out-of-hospital cardiac arrest patients.

“It addresses an understudied patient population, and the second element is that sometimes things you do out of ordinary application – so, the application of oxygen – may have beneficial but also adverse impact,” Dr. Windecker said. “So, to study this in a randomized clinical trial is really important.”

Additionally, he highlighted REVIVED, which will be presented in Hot Line 3 and is the first trial to examine percutaneous coronary intervention (PCI) with optimal medical therapy (OMT) versus OMT alone in the setting of severe ischemic cardiomyopathy.

“We have data from the STICH trial, where surgical revascularization was investigated in ischemic cardiomyopathy, but the open question is: What about PCI as revascularization?” Dr. Windecker said. “The other reason it’s interesting is that we have these evidence-based drugs that have dramatically improved outcomes in patients with heart failure, and REVIVED certainly has been conducted now in an era where at least some of these drugs are more systematically implemented.”

Rounding out this session are the Scottish ALL-HEART study of allopurinol in ischemic heart disease and EchoNet-RCT, looking at whether artificial intelligence (AI) can improve the accuracy of echocardiograms.

Hot Line 4 features DELIVER, a phase 3 trial of the SGLT2 inhibitor dapagliflozin (Farxiga) in HF with preserved or mildly reduced ejection fraction. Topline results, released in May, showed that the study has met its primary endpoint of cardiovascular death or worsening HF.

Dr. Windecker said DELIVER will be a “highlight” of the meeting, particularly because EMPEROR-Preserved, presented at ESC 2021, showed a benefit for another SGLT2 inhibitor, empagliflozin, in this very specific setting. Two prespecified analyses will also be presented, pooling data from EMPEROR-Preserved and from the DAPA-HF study of dapagliflozin in patients with reduced EF. “This will be a session very rich in terms of information.”

Another not-to-be-missed session is Hot Line 5, which will focus on antithrombotic therapy, according to Dr. Windecker, who will cochair the Sunday, Aug. 28 session.

First up is the investigator-initiated INVICTUS-VKA, testing rivaroxaban noninferiority versus standard vitamin K antagonists in patients with atrial fibrillation (AFib) and rheumatic heart disease, a setting in which non–vitamin K antagonists have not been sufficiently tested.

This is followed by three phase 2 trials – PACIFIC-AMI, PACIFIC-STROKE, and AXIOMATIC-SSP – investigating the novel factor XIa inhibitors BAY 2433334 and BMS-986177 in patients with myocardial infarction or stroke.
 

Hot Line sessions 6-10

Sunday’s Hot Line 6 takes another look at smartphone-based AFib screening in eBRAVE-HF, use of causal AI to improve the validity of cardiovascular risk prediction, and AI-enhanced detection of aortic stenosis.

Hot Line 7 rounds out the day, putting coronary imaging center stage. It includes perfusion scanning with MR or PET after a positive angiogram in DanNICAD-2, the PET tracer 18F-sodium fluoride as a marker of high-risk coronary plaques in patients with recent MIs in PREFFIR, and fractional flow reserve- versus angiography-guided PCI in acute MI with multivessel disease in FRAME-AMI.

After a weekend of top-notch science and, no doubt, a spot of revelry, the focus returns on Monday, Aug. 29 to three Hot Line sessions. The first of these, Hot Line 8, updates five clinical trials, including 5-year outcomes from ISCHEMIA-CKD EXTEND, 15-month results from MASTER DAPT, and primary results from FOURIER-OLE, the open-label extension study of evolocumab out to 5 years in approximately 1,600 study participants.

The session closes out with causes of mortality in the FIDELITY trial of finerenone and a win-ratio analysis of PARADISE-MI.

Hot Line 9, billed as an “evidence synthesis on clinically important questions,” includes a Cholesterol Treatment Trialists’ (CTT) Collaboration meta-analysis on the effects of statins on muscle symptoms and a meta-analysis of angiotensin-receptor blockers and beta-blockers in Marfan syndrome from the Marfan Treatment Trialists’ Collaboration.

Also featured is evidence on radial versus femoral access for coronary procedures, and PANTHER, a patient-level meta-analysis of aspirin or P2Y12 inhibitor monotherapy as secondary prevention in patients with established coronary artery disease.

COVID-19, deeply rooted in the minds of attendees and considered in 52 separate sessions, takes over the final Hot Line session of the Congress. Hot Line 10 will report on antithrombotic therapy in critically ill patients in COVID-PACT and on anti-inflammatory therapy with colchicine and antithrombotic therapy with aspirin alone or in combination with rivaroxaban in the ACT inpatient and outpatient trials. Although such early trials have been largely negative, the latest details will be interesting to see, Dr. Windecker suggested.

In terms of COVID-19 protocols, ESC will recommend but not mandate masks and will have test kits available should attendees wish to have a test or if they become symptomatic, he noted.
 

New guidelines released

Four new ESC guidelines will be released during the congress on cardio-oncology, ventricular arrhythmias and sudden cardiac death, pulmonary hypertension, and cardiovascular assessment and management of patients undergoing noncardiac surgery.

In addition to a guideline overview on Friday, one guideline will be featured each day in a 1-hour session, with additional time for discussions with guideline task force members, and six sessions devoted to the implementation of existing guidelines in clinical practice.

The ESC already has a position paper on cardio-oncology, but now, for the first time, has a full guideline with formal laws and level-of-evidence recommendations, Dr. Windecker pointed out.

“I think what will be the great asset, not only of the guideline but out of this emerging field, is that people in the future will probably not only be treated when it’s too late or suffer from toxicity but that there will be screening, and people will be aware before the implementation of therapy,” he added.

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

Adults aged 85 years and older who logged an hour or more of walking each week had a 40% reduced risk of all-cause mortality compared with less active peers, according to data from more than 7,000 individuals.

“Aging is accompanied by reduced physical activity and increased sedentary behavior, and reduced physical activity is associated with decreased life expectancy,” Moo-Nyun Jin, MD, of Inje University Sanggye Paik Hospital, Seoul, South Korea, said in an interview.

Reduced physical activity was especially likely in the elderly during the COVID-19 pandemic, he added.

oneinchpunch/Thinkstock

“Promoting walking may be a simple way to help older adults avoid inactivity and encourage an active lifestyle for all-cause and cardiovascular mortality risk reduction,” Dr. Jin said.

Although walking is generally an easy form of exercise for the older adult population, the specific benefit of walking on reducing mortality has not been well studied, according to Dr. Jin and colleagues.

For adults of any age, current guidelines recommend at least 150 minutes per week of moderate activity or 75 minutes per week of vigorous activity, but the amount of physical activity tends to decline with age, and activity recommendations are more difficult to meet, the authors wrote in a press release accompanying their study.

In the study, to be presented at the European Society of Cardiology Congress on Aug. 28 (Abstract 85643), the researchers reviewed data from 7,047 adults aged 85 years and older who participated in the Korean National Health Screening Program. The average age of the study population was 87 years, and 68% were women. Participants completed questionnaires about the amount of time spent in leisure time activities each week, including walking at a slow pace, moderate activity (such as cycling or brisk walking), and vigorous activity (such as running).

Those who walked at a slow pace for at least 1 hour per week had a 40% reduced risk of all-cause mortality and a 39% reduced risk of cardiovascular mortality, compared with inactive participants.

The proportions of participants who reported walking, moderate activity,­ and vigorous ­intensity physical activity were 42.5%, 14.7%, and 11.0%, respectively. Roughly one-third (33%) of those who reported slow walking each week also reported moderate or vigorous physical activity.

However, walking for 1 hour per week significantly reduced the risk for all-cause mortality and cardiovascular mortality among individuals who reported walking only, without other moderate or vigorous physical activity (hazard ratio, 0.50 and 0.46, respectively).

“Walking was linked with a lower likelihood of dying in older adults, regardless of whether or not they did any moderate to vigorous intensity physical activity,” Dr. Jin told this news organization. “Our study indicates that walking even just 1 hour every week is advantageous to those aged 85 years and older compared to being inactive.”

The hour of walking need not be in long bouts, 10 minutes each day will do, Dr. Jin added.

The participants were divided into five groups based on reported amount of weekly walking. More than half (57.5%) reported no slow walking, 8.5% walked less than 1 hour per week, 12.0% walked 1-2 hours, 8.7% walked 2-3 hours, and 13.3% walked more than 3 hours.

Although the study was limited by the reliance on self-reports, the results were strengthened by the large sample size and support the value of easy walking for adults aged 85 years and older compared to being inactive.

“Walking may present an opportunity for promoting physical activity among the elderly population, offering a simple way to avoid inactivity and increase physical activity,” said Dr. Jin. However, more research is needed to evaluate the association between mortality and walking by objective measurement of walking levels, using a device such as a smart watch, he noted.

 

Results are preliminary

“This is an observational study, not an experiment, so it means causality cannot be presumed,” said Maria Fiatarone Singh, MD, a geriatrician with a focus on exercise physiology at the University of Sydney, in an interview. “In other words, it is possible that diseases resulting in mortality prevented people from walking rather than the other way around,” she noted. The only published experimental study on exercise and mortality in older adults was conducted by Dr. Fiatarone Singh and colleagues in Norway. In that study, published in the British Medical Journal in 2020, high-intensity training programs were associated with reduced all-cause mortality compared with inactive controls and individuals who engaged in moderate intensity exercise.

The current study “would have needed to control for many factors related to mortality, such as cardiovascular disease, hypertension, diabetes, malnutrition, and dementia to see what residual benefit might be related to walking,” Dr. Fiatarone Singh said.

“Although walking seems easy and safe, in fact people who are frail, sarcopenic, osteoporotic, or have fallen are recommended to do resistance and balance training rather than walking, and add walking later when they are able to do it safely,” she emphasized.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Fiatarone Singh had no financial conflicts to disclose.

Adults aged 85 years and older who logged an hour or more of walking each week had a 40% reduced risk of all-cause mortality compared with less active peers, according to data from more than 7,000 individuals.

“Aging is accompanied by reduced physical activity and increased sedentary behavior, and reduced physical activity is associated with decreased life expectancy,” Moo-Nyun Jin, MD, of Inje University Sanggye Paik Hospital, Seoul, South Korea, said in an interview.

Reduced physical activity was especially likely in the elderly during the COVID-19 pandemic, he added.

oneinchpunch/Thinkstock

“Promoting walking may be a simple way to help older adults avoid inactivity and encourage an active lifestyle for all-cause and cardiovascular mortality risk reduction,” Dr. Jin said.

Although walking is generally an easy form of exercise for the older adult population, the specific benefit of walking on reducing mortality has not been well studied, according to Dr. Jin and colleagues.

For adults of any age, current guidelines recommend at least 150 minutes per week of moderate activity or 75 minutes per week of vigorous activity, but the amount of physical activity tends to decline with age, and activity recommendations are more difficult to meet, the authors wrote in a press release accompanying their study.

In the study, to be presented at the European Society of Cardiology Congress on Aug. 28 (Abstract 85643), the researchers reviewed data from 7,047 adults aged 85 years and older who participated in the Korean National Health Screening Program. The average age of the study population was 87 years, and 68% were women. Participants completed questionnaires about the amount of time spent in leisure time activities each week, including walking at a slow pace, moderate activity (such as cycling or brisk walking), and vigorous activity (such as running).

Those who walked at a slow pace for at least 1 hour per week had a 40% reduced risk of all-cause mortality and a 39% reduced risk of cardiovascular mortality, compared with inactive participants.

The proportions of participants who reported walking, moderate activity,­ and vigorous ­intensity physical activity were 42.5%, 14.7%, and 11.0%, respectively. Roughly one-third (33%) of those who reported slow walking each week also reported moderate or vigorous physical activity.

However, walking for 1 hour per week significantly reduced the risk for all-cause mortality and cardiovascular mortality among individuals who reported walking only, without other moderate or vigorous physical activity (hazard ratio, 0.50 and 0.46, respectively).

“Walking was linked with a lower likelihood of dying in older adults, regardless of whether or not they did any moderate to vigorous intensity physical activity,” Dr. Jin told this news organization. “Our study indicates that walking even just 1 hour every week is advantageous to those aged 85 years and older compared to being inactive.”

The hour of walking need not be in long bouts, 10 minutes each day will do, Dr. Jin added.

The participants were divided into five groups based on reported amount of weekly walking. More than half (57.5%) reported no slow walking, 8.5% walked less than 1 hour per week, 12.0% walked 1-2 hours, 8.7% walked 2-3 hours, and 13.3% walked more than 3 hours.

Although the study was limited by the reliance on self-reports, the results were strengthened by the large sample size and support the value of easy walking for adults aged 85 years and older compared to being inactive.

“Walking may present an opportunity for promoting physical activity among the elderly population, offering a simple way to avoid inactivity and increase physical activity,” said Dr. Jin. However, more research is needed to evaluate the association between mortality and walking by objective measurement of walking levels, using a device such as a smart watch, he noted.

 

Results are preliminary

“This is an observational study, not an experiment, so it means causality cannot be presumed,” said Maria Fiatarone Singh, MD, a geriatrician with a focus on exercise physiology at the University of Sydney, in an interview. “In other words, it is possible that diseases resulting in mortality prevented people from walking rather than the other way around,” she noted. The only published experimental study on exercise and mortality in older adults was conducted by Dr. Fiatarone Singh and colleagues in Norway. In that study, published in the British Medical Journal in 2020, high-intensity training programs were associated with reduced all-cause mortality compared with inactive controls and individuals who engaged in moderate intensity exercise.

The current study “would have needed to control for many factors related to mortality, such as cardiovascular disease, hypertension, diabetes, malnutrition, and dementia to see what residual benefit might be related to walking,” Dr. Fiatarone Singh said.

“Although walking seems easy and safe, in fact people who are frail, sarcopenic, osteoporotic, or have fallen are recommended to do resistance and balance training rather than walking, and add walking later when they are able to do it safely,” she emphasized.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Fiatarone Singh had no financial conflicts to disclose.

Adults aged 85 years and older who logged an hour or more of walking each week had a 40% reduced risk of all-cause mortality compared with less active peers, according to data from more than 7,000 individuals.

“Aging is accompanied by reduced physical activity and increased sedentary behavior, and reduced physical activity is associated with decreased life expectancy,” Moo-Nyun Jin, MD, of Inje University Sanggye Paik Hospital, Seoul, South Korea, said in an interview.

Reduced physical activity was especially likely in the elderly during the COVID-19 pandemic, he added.

oneinchpunch/Thinkstock

“Promoting walking may be a simple way to help older adults avoid inactivity and encourage an active lifestyle for all-cause and cardiovascular mortality risk reduction,” Dr. Jin said.

Although walking is generally an easy form of exercise for the older adult population, the specific benefit of walking on reducing mortality has not been well studied, according to Dr. Jin and colleagues.

For adults of any age, current guidelines recommend at least 150 minutes per week of moderate activity or 75 minutes per week of vigorous activity, but the amount of physical activity tends to decline with age, and activity recommendations are more difficult to meet, the authors wrote in a press release accompanying their study.

In the study, to be presented at the European Society of Cardiology Congress on Aug. 28 (Abstract 85643), the researchers reviewed data from 7,047 adults aged 85 years and older who participated in the Korean National Health Screening Program. The average age of the study population was 87 years, and 68% were women. Participants completed questionnaires about the amount of time spent in leisure time activities each week, including walking at a slow pace, moderate activity (such as cycling or brisk walking), and vigorous activity (such as running).

Those who walked at a slow pace for at least 1 hour per week had a 40% reduced risk of all-cause mortality and a 39% reduced risk of cardiovascular mortality, compared with inactive participants.

The proportions of participants who reported walking, moderate activity,­ and vigorous ­intensity physical activity were 42.5%, 14.7%, and 11.0%, respectively. Roughly one-third (33%) of those who reported slow walking each week also reported moderate or vigorous physical activity.

However, walking for 1 hour per week significantly reduced the risk for all-cause mortality and cardiovascular mortality among individuals who reported walking only, without other moderate or vigorous physical activity (hazard ratio, 0.50 and 0.46, respectively).

“Walking was linked with a lower likelihood of dying in older adults, regardless of whether or not they did any moderate to vigorous intensity physical activity,” Dr. Jin told this news organization. “Our study indicates that walking even just 1 hour every week is advantageous to those aged 85 years and older compared to being inactive.”

The hour of walking need not be in long bouts, 10 minutes each day will do, Dr. Jin added.

The participants were divided into five groups based on reported amount of weekly walking. More than half (57.5%) reported no slow walking, 8.5% walked less than 1 hour per week, 12.0% walked 1-2 hours, 8.7% walked 2-3 hours, and 13.3% walked more than 3 hours.

Although the study was limited by the reliance on self-reports, the results were strengthened by the large sample size and support the value of easy walking for adults aged 85 years and older compared to being inactive.

“Walking may present an opportunity for promoting physical activity among the elderly population, offering a simple way to avoid inactivity and increase physical activity,” said Dr. Jin. However, more research is needed to evaluate the association between mortality and walking by objective measurement of walking levels, using a device such as a smart watch, he noted.

 

Results are preliminary

“This is an observational study, not an experiment, so it means causality cannot be presumed,” said Maria Fiatarone Singh, MD, a geriatrician with a focus on exercise physiology at the University of Sydney, in an interview. “In other words, it is possible that diseases resulting in mortality prevented people from walking rather than the other way around,” she noted. The only published experimental study on exercise and mortality in older adults was conducted by Dr. Fiatarone Singh and colleagues in Norway. In that study, published in the British Medical Journal in 2020, high-intensity training programs were associated with reduced all-cause mortality compared with inactive controls and individuals who engaged in moderate intensity exercise.

The current study “would have needed to control for many factors related to mortality, such as cardiovascular disease, hypertension, diabetes, malnutrition, and dementia to see what residual benefit might be related to walking,” Dr. Fiatarone Singh said.

“Although walking seems easy and safe, in fact people who are frail, sarcopenic, osteoporotic, or have fallen are recommended to do resistance and balance training rather than walking, and add walking later when they are able to do it safely,” she emphasized.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Fiatarone Singh had no financial conflicts to disclose.