Heart Failure

Drinking two to three daily cups of – ground, instant, or decaffeinated – is associated with significant reductions in new cardiovascular disease (CVD) and mortality risk, compared with avoiding coffee, a new analysis of the prospective UK Biobank suggests.

Ground and instant coffee, but not decaffeinated coffee, also was associated with reduced risk of new-onset arrhythmia, including atrial fibrillation.

Visual_Intermezzo/iStock/Getty Images Plus

“Our study is the first to look at differences in coffee subtypes to tease out important differences which may explain some of the mechanisms through which coffee works,” Peter M. Kistler, MD, of the Alfred Hospital and Baker Heart and Diabetes Institute, Melbourne, Australia, told this news organization.

“Daily coffee intake should not be discouraged by physicians but rather considered part of a healthy diet,” Dr. Kistler said.

“This study supports that coffee is safe and even potentially beneficial, which is consistent with most of the prior evidence,” Carl “Chip” Lavie, MD, who wasn’t involved in the study, told this news organization.

“We do not prescribe coffee to patients, but for the majority who like coffee, they can be encouraged it is fine to take a few cups daily,” said Dr. Lavie, with the Ochsner Heart and Vascular Institute in New Orleans.

The study was published online in the European Journal of Preventive Cardiology.

 

Clear cardiovascular benefits

A total of 449,563 UK Biobank participants (median age 58 years; 55% women), who were free of arrhythmias or other CVD at baseline, reported in questionnaires their level of daily coffee intake and preferred type of coffee.

During more than 12.5 years of follow-up, 27,809 participants (6.2%) died.

Drinking one to five cups per day of ground or instant coffee (but not decaffeinated coffee) was associated with a significant reduction in incident arrhythmia. The lowest risk was with four to five cups per day for ground coffee (hazard ratio [HR] 0.83; 95% confidence interval [CI], 0.76-0.91; P < .0001) and two to three cups per day for instant coffee (HR, 0.88; 95% CI, 0.85-0.92; P < .0001).

Habitual coffee drinking of up to five cups perday was also associated with significant reductions in the risk of incident CVD, when compared with nondrinkers.

Significant reductions in the risk of incident coronary heart disease (CHD) were associated with habitual coffee intake of up to five cups per day, with the lowest risk for CHD observed in those who consumed two to three cups per day (HR 0.89; 95% CI, 0.86-0.91; P < .0001).

Coffee consumption at all levels was linked to significant reduction in the risk of congestive cardiac failure (CCF) and ischemic stroke. The lowest risks were observed in those who consumed two to three cups per day, with HR, 0.83 (95% CI, 0.79-0.87; P < .0001) for CCF and HR, 0.84 (95% CI, 0.78-0.90; P < .0001) for ischemic stroke.

Death from any cause was significantly reduced for all coffee subtypes, with the greatest risk reduction seen with two to three cups per day for decaffeinated (HR, 0.86; 95% CI, 0.81-0.91; P < .0001); ground (HR, 0.73; 95% CI, 0.69-0.78; P < .0001); and instant coffee (HR, 0.89; 95% CI, 0.86-0.93; P < .0001).

“Coffee consumption is associated with cardiovascular benefits and should not empirically be discontinued in those with underlying heart rhythm disorders or cardiovascular disease,” Dr. Kistler told this news organization.

Plausible mechanisms

There are a number of proposed mechanisms to explain the benefits of coffee on CVD.

“Caffeine has antiarrhythmic properties through adenosine A1 and A2A receptor inhibition, hence the difference in effects of decaf vs. full-strength coffee on heart rhythm disorders,” Dr. Kistler explained.

Coffee has vasodilatory effects and coffee also contains antioxidant polyphenols, which reduce oxidative stress and modulate metabolism.

“The explanation for improved survival with habitual coffee consumption remains unclear,” Dr. Kistler said.

“Putative mechanisms include improved endothelial function, circulating antioxidants, improved insulin sensitivity, and reduced inflammation. Another potential mechanism includes the beneficial effects of coffee on metabolic syndrome,” he said.

“Caffeine has a role in weight loss through inhibition of gut fatty acid absorption and increase in basal metabolic rate. Furthermore, coffee has been associated with a significantly lower incidence of type 2 diabetes mellitus,” Dr. Kistler added.
 

Direction of relationship unclear

Charlotte Mills, PhD, University of Reading, England, said this study “adds to the body of evidence from observational trials associating moderate coffee consumption with cardioprotection, which looks promising.”

However, with the observational design, it’s unclear “which direction the relationship goes – for example, does coffee make you healthy or do inherently healthier people consume coffee? Randomized controlled trials are needed to fully understand the relationship between coffee and health before recommendations can be made,” Dr. Mills told the UK nonprofit Science Media Centre.

Annette Creedon, PhD, nutrition scientist with the British Nutrition Foundation, said it’s possible that respondents over- or underestimated the amount of coffee that they were consuming at the start of the study when they self-reported their intake.

“It is therefore difficult to determine whether the outcomes can be directly associated with the behaviors in coffee consumption reported at the start of the study,” she told the Science Media Centre.

The study had no funding. Dr. Kistler has received funding from Abbott Medical for consultancy and speaking engagements and fellowship support from Biosense Webster. Dr. Lavie has no relevant disclosures. Dr. Mills has worked in collaboration with Nestle on research relating to coffee and health funded by UKRI. Dr. Creedon has reported no relevant financial relationships.

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

Drinking two to three daily cups of – ground, instant, or decaffeinated – is associated with significant reductions in new cardiovascular disease (CVD) and mortality risk, compared with avoiding coffee, a new analysis of the prospective UK Biobank suggests.

Ground and instant coffee, but not decaffeinated coffee, also was associated with reduced risk of new-onset arrhythmia, including atrial fibrillation.

Visual_Intermezzo/iStock/Getty Images Plus

“Our study is the first to look at differences in coffee subtypes to tease out important differences which may explain some of the mechanisms through which coffee works,” Peter M. Kistler, MD, of the Alfred Hospital and Baker Heart and Diabetes Institute, Melbourne, Australia, told this news organization.

“Daily coffee intake should not be discouraged by physicians but rather considered part of a healthy diet,” Dr. Kistler said.

“This study supports that coffee is safe and even potentially beneficial, which is consistent with most of the prior evidence,” Carl “Chip” Lavie, MD, who wasn’t involved in the study, told this news organization.

“We do not prescribe coffee to patients, but for the majority who like coffee, they can be encouraged it is fine to take a few cups daily,” said Dr. Lavie, with the Ochsner Heart and Vascular Institute in New Orleans.

The study was published online in the European Journal of Preventive Cardiology.

 

Clear cardiovascular benefits

A total of 449,563 UK Biobank participants (median age 58 years; 55% women), who were free of arrhythmias or other CVD at baseline, reported in questionnaires their level of daily coffee intake and preferred type of coffee.

During more than 12.5 years of follow-up, 27,809 participants (6.2%) died.

Drinking one to five cups per day of ground or instant coffee (but not decaffeinated coffee) was associated with a significant reduction in incident arrhythmia. The lowest risk was with four to five cups per day for ground coffee (hazard ratio [HR] 0.83; 95% confidence interval [CI], 0.76-0.91; P < .0001) and two to three cups per day for instant coffee (HR, 0.88; 95% CI, 0.85-0.92; P < .0001).

Habitual coffee drinking of up to five cups perday was also associated with significant reductions in the risk of incident CVD, when compared with nondrinkers.

Significant reductions in the risk of incident coronary heart disease (CHD) were associated with habitual coffee intake of up to five cups per day, with the lowest risk for CHD observed in those who consumed two to three cups per day (HR 0.89; 95% CI, 0.86-0.91; P < .0001).

Coffee consumption at all levels was linked to significant reduction in the risk of congestive cardiac failure (CCF) and ischemic stroke. The lowest risks were observed in those who consumed two to three cups per day, with HR, 0.83 (95% CI, 0.79-0.87; P < .0001) for CCF and HR, 0.84 (95% CI, 0.78-0.90; P < .0001) for ischemic stroke.

Death from any cause was significantly reduced for all coffee subtypes, with the greatest risk reduction seen with two to three cups per day for decaffeinated (HR, 0.86; 95% CI, 0.81-0.91; P < .0001); ground (HR, 0.73; 95% CI, 0.69-0.78; P < .0001); and instant coffee (HR, 0.89; 95% CI, 0.86-0.93; P < .0001).

“Coffee consumption is associated with cardiovascular benefits and should not empirically be discontinued in those with underlying heart rhythm disorders or cardiovascular disease,” Dr. Kistler told this news organization.

Plausible mechanisms

There are a number of proposed mechanisms to explain the benefits of coffee on CVD.

“Caffeine has antiarrhythmic properties through adenosine A1 and A2A receptor inhibition, hence the difference in effects of decaf vs. full-strength coffee on heart rhythm disorders,” Dr. Kistler explained.

Coffee has vasodilatory effects and coffee also contains antioxidant polyphenols, which reduce oxidative stress and modulate metabolism.

“The explanation for improved survival with habitual coffee consumption remains unclear,” Dr. Kistler said.

“Putative mechanisms include improved endothelial function, circulating antioxidants, improved insulin sensitivity, and reduced inflammation. Another potential mechanism includes the beneficial effects of coffee on metabolic syndrome,” he said.

“Caffeine has a role in weight loss through inhibition of gut fatty acid absorption and increase in basal metabolic rate. Furthermore, coffee has been associated with a significantly lower incidence of type 2 diabetes mellitus,” Dr. Kistler added.
 

Direction of relationship unclear

Charlotte Mills, PhD, University of Reading, England, said this study “adds to the body of evidence from observational trials associating moderate coffee consumption with cardioprotection, which looks promising.”

However, with the observational design, it’s unclear “which direction the relationship goes – for example, does coffee make you healthy or do inherently healthier people consume coffee? Randomized controlled trials are needed to fully understand the relationship between coffee and health before recommendations can be made,” Dr. Mills told the UK nonprofit Science Media Centre.

Annette Creedon, PhD, nutrition scientist with the British Nutrition Foundation, said it’s possible that respondents over- or underestimated the amount of coffee that they were consuming at the start of the study when they self-reported their intake.

“It is therefore difficult to determine whether the outcomes can be directly associated with the behaviors in coffee consumption reported at the start of the study,” she told the Science Media Centre.

The study had no funding. Dr. Kistler has received funding from Abbott Medical for consultancy and speaking engagements and fellowship support from Biosense Webster. Dr. Lavie has no relevant disclosures. Dr. Mills has worked in collaboration with Nestle on research relating to coffee and health funded by UKRI. Dr. Creedon has reported no relevant financial relationships.

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

Drinking two to three daily cups of – ground, instant, or decaffeinated – is associated with significant reductions in new cardiovascular disease (CVD) and mortality risk, compared with avoiding coffee, a new analysis of the prospective UK Biobank suggests.

Ground and instant coffee, but not decaffeinated coffee, also was associated with reduced risk of new-onset arrhythmia, including atrial fibrillation.

Visual_Intermezzo/iStock/Getty Images Plus

“Our study is the first to look at differences in coffee subtypes to tease out important differences which may explain some of the mechanisms through which coffee works,” Peter M. Kistler, MD, of the Alfred Hospital and Baker Heart and Diabetes Institute, Melbourne, Australia, told this news organization.

“Daily coffee intake should not be discouraged by physicians but rather considered part of a healthy diet,” Dr. Kistler said.

“This study supports that coffee is safe and even potentially beneficial, which is consistent with most of the prior evidence,” Carl “Chip” Lavie, MD, who wasn’t involved in the study, told this news organization.

“We do not prescribe coffee to patients, but for the majority who like coffee, they can be encouraged it is fine to take a few cups daily,” said Dr. Lavie, with the Ochsner Heart and Vascular Institute in New Orleans.

The study was published online in the European Journal of Preventive Cardiology.

 

Clear cardiovascular benefits

A total of 449,563 UK Biobank participants (median age 58 years; 55% women), who were free of arrhythmias or other CVD at baseline, reported in questionnaires their level of daily coffee intake and preferred type of coffee.

During more than 12.5 years of follow-up, 27,809 participants (6.2%) died.

Drinking one to five cups per day of ground or instant coffee (but not decaffeinated coffee) was associated with a significant reduction in incident arrhythmia. The lowest risk was with four to five cups per day for ground coffee (hazard ratio [HR] 0.83; 95% confidence interval [CI], 0.76-0.91; P < .0001) and two to three cups per day for instant coffee (HR, 0.88; 95% CI, 0.85-0.92; P < .0001).

Habitual coffee drinking of up to five cups perday was also associated with significant reductions in the risk of incident CVD, when compared with nondrinkers.

Significant reductions in the risk of incident coronary heart disease (CHD) were associated with habitual coffee intake of up to five cups per day, with the lowest risk for CHD observed in those who consumed two to three cups per day (HR 0.89; 95% CI, 0.86-0.91; P < .0001).

Coffee consumption at all levels was linked to significant reduction in the risk of congestive cardiac failure (CCF) and ischemic stroke. The lowest risks were observed in those who consumed two to three cups per day, with HR, 0.83 (95% CI, 0.79-0.87; P < .0001) for CCF and HR, 0.84 (95% CI, 0.78-0.90; P < .0001) for ischemic stroke.

Death from any cause was significantly reduced for all coffee subtypes, with the greatest risk reduction seen with two to three cups per day for decaffeinated (HR, 0.86; 95% CI, 0.81-0.91; P < .0001); ground (HR, 0.73; 95% CI, 0.69-0.78; P < .0001); and instant coffee (HR, 0.89; 95% CI, 0.86-0.93; P < .0001).

“Coffee consumption is associated with cardiovascular benefits and should not empirically be discontinued in those with underlying heart rhythm disorders or cardiovascular disease,” Dr. Kistler told this news organization.

Plausible mechanisms

There are a number of proposed mechanisms to explain the benefits of coffee on CVD.

“Caffeine has antiarrhythmic properties through adenosine A1 and A2A receptor inhibition, hence the difference in effects of decaf vs. full-strength coffee on heart rhythm disorders,” Dr. Kistler explained.

Coffee has vasodilatory effects and coffee also contains antioxidant polyphenols, which reduce oxidative stress and modulate metabolism.

“The explanation for improved survival with habitual coffee consumption remains unclear,” Dr. Kistler said.

“Putative mechanisms include improved endothelial function, circulating antioxidants, improved insulin sensitivity, and reduced inflammation. Another potential mechanism includes the beneficial effects of coffee on metabolic syndrome,” he said.

“Caffeine has a role in weight loss through inhibition of gut fatty acid absorption and increase in basal metabolic rate. Furthermore, coffee has been associated with a significantly lower incidence of type 2 diabetes mellitus,” Dr. Kistler added.
 

Direction of relationship unclear

Charlotte Mills, PhD, University of Reading, England, said this study “adds to the body of evidence from observational trials associating moderate coffee consumption with cardioprotection, which looks promising.”

However, with the observational design, it’s unclear “which direction the relationship goes – for example, does coffee make you healthy or do inherently healthier people consume coffee? Randomized controlled trials are needed to fully understand the relationship between coffee and health before recommendations can be made,” Dr. Mills told the UK nonprofit Science Media Centre.

Annette Creedon, PhD, nutrition scientist with the British Nutrition Foundation, said it’s possible that respondents over- or underestimated the amount of coffee that they were consuming at the start of the study when they self-reported their intake.

“It is therefore difficult to determine whether the outcomes can be directly associated with the behaviors in coffee consumption reported at the start of the study,” she told the Science Media Centre.

The study had no funding. Dr. Kistler has received funding from Abbott Medical for consultancy and speaking engagements and fellowship support from Biosense Webster. Dr. Lavie has no relevant disclosures. Dr. Mills has worked in collaboration with Nestle on research relating to coffee and health funded by UKRI. Dr. Creedon has reported no relevant financial relationships.

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

A look at the top cardiovascular disease (CVD) diagnoses in U.S. emergency departments (EDs) suggests that many heart-related emergencies are due to poorly controlled high blood pressure.

In a study of more than 20 million ED visits, about one-third of CVD-related ED visits in the United States were for hypertension-related conditions.

Overall, 13% of ED visits, representing more than 2.7 million individuals, were for essential hypertension.

Nationwide sample

The researchers studied more than 20.6 million ED encounters in adults with a primary CVD diagnosis using data from the Nationwide Emergency Department Sample between 2016 and 2018.

In the sample, 49% were women, and the median age was 67 years. Men had poorer overall baseline cardiometabolic profiles, but women had higher rates of obesity, hypertension, and cerebrovascular disease. The majority had Medicare or Medicaid insurance.

In women, essential hypertension was the most common reason for an ED visit (16%), followed by hypertensive heart or kidney disease (14%) and atrial fibrillation (AF)/flutter (10%).

In men, the top three reasons were hypertensive heart or kidney disease (15%), essential hypertension (11%), and acute myocardial infarction (AMI, 11%).

On presentation, women were significantly more likely to have essential hypertension, hypertensive crisis, AF/flutter, supraventricular tachycardia, pulmonary embolism, or ischemic stroke, while men were more likely to have AMI, or cardiac arrest.

“Previous studies have shown sex differences in patterns of CVD among hospitalized patients,” Dr. Mamas noted. “However, examining CVD encounters in the ED provides a more complete picture of the cardiovascular healthcare needs of men and women, as it captures encounters prior to hospitalization.”

He noted that previous studies of CVD emergency visits are limited to suspected MI visits. “Therefore, this analysis of 15 CVD conditions helps to better understand the full spectrum of acute CVD needs, including sex disparities in hospitalization and risk of death,” Dr. Mamas said.
 

Sex differences in outcomes

The study found that outcomes from the emergency CVD visits were slightly different for men and women.

Overall, women were less likely than were men to die (3.3% vs. 4.3%) or be hospitalized (49.1% vs. 52.3%) after an ED visit for CVD. The difference may be due to women’s generally lower-risk diagnoses, Dr. Mamas said, but there could be an underestimation of deaths in women.

In logistic regression models adjusted for baseline covariates, women with intracranial hemorrhage (ICH) had a higher risk of being admitted to hospital or dying compared with men with ICH.

Men were more likely to die if they presented with hypertensive heart or kidney disease, AF/flutter, AMI or cardiac arrest, the researchers found. 

“We did not track deaths outside of the hospital setting,” Dr. Mamas pointed out. Given past evidence that women are more likely to be inappropriately discharged from the ED, and strong evidence for the systemic undertreatment of women, further study is warranted to track outcomes beyond the ED visit,” he added.

The researchers called for further research into understanding the underlying factors driving the differences in CVD patterns and outcomes between men and women.

Reached for comment, Maryann McLaughlin, MD, a cardiologist at Mount Sinai Hospital, New York, said: “Hypertension is a silent killer” and this study “reiterates that people need to get their blood pressure checked more regularly.

“In the very least, if they do present to the hospital as not feeling well or whatever it is, and they are identified as having high blood pressure, that’s an important opportunity to really teach them about hypertension and have them follow-up with it,” Dr. McLaughlin told this news organization. 

The study was supported by Health Data Research UK. Dr. Keele and Dr. McLaughlin have reported no relevant financial relationships.

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

A look at the top cardiovascular disease (CVD) diagnoses in U.S. emergency departments (EDs) suggests that many heart-related emergencies are due to poorly controlled high blood pressure.

In a study of more than 20 million ED visits, about one-third of CVD-related ED visits in the United States were for hypertension-related conditions.

Overall, 13% of ED visits, representing more than 2.7 million individuals, were for essential hypertension.

Nationwide sample

The researchers studied more than 20.6 million ED encounters in adults with a primary CVD diagnosis using data from the Nationwide Emergency Department Sample between 2016 and 2018.

In the sample, 49% were women, and the median age was 67 years. Men had poorer overall baseline cardiometabolic profiles, but women had higher rates of obesity, hypertension, and cerebrovascular disease. The majority had Medicare or Medicaid insurance.

In women, essential hypertension was the most common reason for an ED visit (16%), followed by hypertensive heart or kidney disease (14%) and atrial fibrillation (AF)/flutter (10%).

In men, the top three reasons were hypertensive heart or kidney disease (15%), essential hypertension (11%), and acute myocardial infarction (AMI, 11%).

On presentation, women were significantly more likely to have essential hypertension, hypertensive crisis, AF/flutter, supraventricular tachycardia, pulmonary embolism, or ischemic stroke, while men were more likely to have AMI, or cardiac arrest.

“Previous studies have shown sex differences in patterns of CVD among hospitalized patients,” Dr. Mamas noted. “However, examining CVD encounters in the ED provides a more complete picture of the cardiovascular healthcare needs of men and women, as it captures encounters prior to hospitalization.”

He noted that previous studies of CVD emergency visits are limited to suspected MI visits. “Therefore, this analysis of 15 CVD conditions helps to better understand the full spectrum of acute CVD needs, including sex disparities in hospitalization and risk of death,” Dr. Mamas said.
 

Sex differences in outcomes

The study found that outcomes from the emergency CVD visits were slightly different for men and women.

Overall, women were less likely than were men to die (3.3% vs. 4.3%) or be hospitalized (49.1% vs. 52.3%) after an ED visit for CVD. The difference may be due to women’s generally lower-risk diagnoses, Dr. Mamas said, but there could be an underestimation of deaths in women.

In logistic regression models adjusted for baseline covariates, women with intracranial hemorrhage (ICH) had a higher risk of being admitted to hospital or dying compared with men with ICH.

Men were more likely to die if they presented with hypertensive heart or kidney disease, AF/flutter, AMI or cardiac arrest, the researchers found. 

“We did not track deaths outside of the hospital setting,” Dr. Mamas pointed out. Given past evidence that women are more likely to be inappropriately discharged from the ED, and strong evidence for the systemic undertreatment of women, further study is warranted to track outcomes beyond the ED visit,” he added.

The researchers called for further research into understanding the underlying factors driving the differences in CVD patterns and outcomes between men and women.

Reached for comment, Maryann McLaughlin, MD, a cardiologist at Mount Sinai Hospital, New York, said: “Hypertension is a silent killer” and this study “reiterates that people need to get their blood pressure checked more regularly.

“In the very least, if they do present to the hospital as not feeling well or whatever it is, and they are identified as having high blood pressure, that’s an important opportunity to really teach them about hypertension and have them follow-up with it,” Dr. McLaughlin told this news organization. 

The study was supported by Health Data Research UK. Dr. Keele and Dr. McLaughlin have reported no relevant financial relationships.

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

A look at the top cardiovascular disease (CVD) diagnoses in U.S. emergency departments (EDs) suggests that many heart-related emergencies are due to poorly controlled high blood pressure.

In a study of more than 20 million ED visits, about one-third of CVD-related ED visits in the United States were for hypertension-related conditions.

Overall, 13% of ED visits, representing more than 2.7 million individuals, were for essential hypertension.

Nationwide sample

The researchers studied more than 20.6 million ED encounters in adults with a primary CVD diagnosis using data from the Nationwide Emergency Department Sample between 2016 and 2018.

In the sample, 49% were women, and the median age was 67 years. Men had poorer overall baseline cardiometabolic profiles, but women had higher rates of obesity, hypertension, and cerebrovascular disease. The majority had Medicare or Medicaid insurance.

In women, essential hypertension was the most common reason for an ED visit (16%), followed by hypertensive heart or kidney disease (14%) and atrial fibrillation (AF)/flutter (10%).

In men, the top three reasons were hypertensive heart or kidney disease (15%), essential hypertension (11%), and acute myocardial infarction (AMI, 11%).

On presentation, women were significantly more likely to have essential hypertension, hypertensive crisis, AF/flutter, supraventricular tachycardia, pulmonary embolism, or ischemic stroke, while men were more likely to have AMI, or cardiac arrest.

“Previous studies have shown sex differences in patterns of CVD among hospitalized patients,” Dr. Mamas noted. “However, examining CVD encounters in the ED provides a more complete picture of the cardiovascular healthcare needs of men and women, as it captures encounters prior to hospitalization.”

He noted that previous studies of CVD emergency visits are limited to suspected MI visits. “Therefore, this analysis of 15 CVD conditions helps to better understand the full spectrum of acute CVD needs, including sex disparities in hospitalization and risk of death,” Dr. Mamas said.
 

Sex differences in outcomes

The study found that outcomes from the emergency CVD visits were slightly different for men and women.

Overall, women were less likely than were men to die (3.3% vs. 4.3%) or be hospitalized (49.1% vs. 52.3%) after an ED visit for CVD. The difference may be due to women’s generally lower-risk diagnoses, Dr. Mamas said, but there could be an underestimation of deaths in women.

In logistic regression models adjusted for baseline covariates, women with intracranial hemorrhage (ICH) had a higher risk of being admitted to hospital or dying compared with men with ICH.

Men were more likely to die if they presented with hypertensive heart or kidney disease, AF/flutter, AMI or cardiac arrest, the researchers found. 

“We did not track deaths outside of the hospital setting,” Dr. Mamas pointed out. Given past evidence that women are more likely to be inappropriately discharged from the ED, and strong evidence for the systemic undertreatment of women, further study is warranted to track outcomes beyond the ED visit,” he added.

The researchers called for further research into understanding the underlying factors driving the differences in CVD patterns and outcomes between men and women.

Reached for comment, Maryann McLaughlin, MD, a cardiologist at Mount Sinai Hospital, New York, said: “Hypertension is a silent killer” and this study “reiterates that people need to get their blood pressure checked more regularly.

“In the very least, if they do present to the hospital as not feeling well or whatever it is, and they are identified as having high blood pressure, that’s an important opportunity to really teach them about hypertension and have them follow-up with it,” Dr. McLaughlin told this news organization. 

The study was supported by Health Data Research UK. Dr. Keele and Dr. McLaughlin have reported no relevant financial relationships.

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

A newly available transcatheter device for edge-to-edge mitral valve (MV) repair, named for a famed scientist-inventor, is similar to the long-available MitraClip (Abbott) for short-term efficacy and safety, suggests an interim but prespecified analysis from a randomized trial.

In its comparison with MitraClip, the PASCAL transcatheter valve repair system (Edwards Lifesciences) was noninferior with respect to 30-day major adverse events and to success at achieving mitral regurgitation (MR) of no more than moderate severity within 6 months. The trial had entered patients with significant, symptomatic degenerative MR considered too high-risk for surgical repair or replacement.

The interim analysis covers 180 of the 300 patients followed in the study, of whom 117 received the PASCAL device and 63 were given MitraClip. Both groups showed significant gains in functional class, symptom status, and quality of life over 6 months, reported D. Scott Lim, MD, University of Virginia Health System Hospital, Charlottesville, and Konstantinos Koulogiannis, MD, Morristown Medical Center, N.J., jointly on Sept. 17 at the Transcatheter Cardiovascular Therapeutics (TCT) 2022 annual meeting in Boston.

Dr. Lim, one of the trial’s principal investigators, is also lead author on its same-day publication in JACC: Cardiovascular Interventions.

Based largely on those results from the CLASP IID pivotal trial, the U.S. Food and Drug Administration recently approved the PASCAL system for use in patients with degenerative MR, Edwards announced on Sept. 15. The device was approved in the European Union on Aug. 17.

MitraClip has been available in various iterations in the United States since 2013 and in Europe since 2008.

“It’s good for the field to be able to say we have two devices that are comparable,” giving clinicians more options, Vinod H. Thourani, MD, Piedmont Heart Institute, Atlanta, told this news organization.

The current analysis shows that “we’ve yet to figure out what patient pathologies will be beneficial” for each of the devices, Dr. Thourani said. “The goal will be to find out if there are certain anatomical considerations where one device is better than the other.”

It will be necessary to study “more patients, a larger cohort, with longer follow-up to allow us to see their true benefits,” he said, as well as to conduct more subgroup analyses. For now, the choice of device will probably be “operator-specific, which they feel comfortable with.”

Dr. Thourani, not an author on the current study, is the U.S. principal investigator for the CLASP IIF study looking at clinical outcomes with the two devices and says he consults for both Edwards and Abbott.

The findings are “preliminary for now,” said Michael Young, MD, Dartmouth-Hitchcock Medical Center, Lebanon, N.H., in part because, like most randomized trials, CLASP IID entered a select, not broadly representative population.

“They want to make, as best as they could, an apples-to-apples comparison, without confounding that might make it more difficult to interpret it afterwards,” Dr. Young, not associated with the trial, told this news organization.

But CLASP IID “did enroll patients that we do see and treat, so undoubtedly it’s a compelling study. We now have another device that is shown to be safe and effective. How we’re going to extrapolate it to all the patients that are being referred to our practices will, I think, be under debate and deliberation.”

The PASCAL and MitraClip devices each may be more suitable for different patients with varying mitral valve pathologies because of differences in their designs, Dr. Lim said. The PASCAL’s relative flexibility might make it preferable in patients with smaller mitral valves, and its ability to elongate during delivery could make it more suitable for patients with chordal-dense areas around the valve, he speculated.

MitraClip, Dr. Lim told this news organization, has a mechanical closure system for anchoring that may make it more appropriate for “more complicated, thicker leaflets with calcium.”

CLASP IID enrolled patients with grade 3+ or 4+ degenerative MR considered to be “at prohibitive surgical risk” at 43 sites in North America and Europe. It randomly assigned them 2-to-1 to receive the PASCAL device or MitraClip.

Either of two PASCAL versions were used, the original device or the “smaller, narrower” PASCAL Ace, Dr. Lim observed. Both versions are covered by the PASCAL Precision System FDA approval. About 40% of patients assigned to MitraClip received older versions of the device and about 60%, more recent versions, as they were entered into practice.

The mean procedure times were 88 minutes for PASCAL and 79 minutes for MitraClip (P = .023), with much of the difference attributable to the earliest PASCAL procedures. Procedure times for the device declined with greater operator experience, the published report states.

Rates of the primary safety endpoint of major adverse events at 30 days were 3.4% for PASCAL and 4.8% for MitraClip. The endpoint was a composite of cardiovascular  mortality, stroke, myocardial infarction, new need for renal replacement therapy, severe bleeding, or nonelective MV reintervention.

The proportion of patients with MR grade 2+ or lower at 6 months, the primary effectiveness endpoint, assessed at a core laboratory, was 96.5% for the PASCAL group over a median follow-up of 179.5 days and 96.8% over a median of 184.5 days for those who received MitraClip.

Comparisons for both primary endpoints met the prespecified criteria for PASCAL noninferiority.

In a secondary analysis, the proportion of PASCAL patients with MR grade 1+ or less held about steady from postprocedure discharge out to 6 months, at 87.2% and 83.7%, respectively (P = .317).

But  whereas 88.5% of MitraClip patients had MR grade 1+ or better at discharge, 71.2% were at that grade by 6 months (P = .003). That apparent hemodynamic deterioration raised some eyebrows at the TCT sessions as a potential sign that PASCAL functional results are more durable.

That sort of judgment is premature, offered Anita W. Asgar, MD, MSc, Montreal Heart Institute, Quebec City, as an invited discussant after the CLASP IID trial’s formal presentation at the meeting, which was sponsored by the Cardiovascular Research Foundation.

The trial is notable in part for “showing how safe this procedure is and how successful it is for these patients – this is phenomenal,” she said, but “I would caution comparing one device being better than another with such a small number of patients.”

MitraClip, Dr. Young observed, “has been, up to this point, our only option for edge-to-edge repair of the mitral valve. And many of us have years of experience and a lot of patients that we treat with that device.” His center hasn’t yet used PASCAL, but that may change as the field gains more familiarity with the device. Operators may use either device in different cases, he said.

“Depending on the program, and depending on the volume of mitral patients that you see and edge-to-edge repair that you do, it could be that you stick with one, or switch to another, or you integrate both of them and try to decide which patients might be better suited for one or the other.”

CLASP IID was sponsored by Edwards Lifesciences. Dr. Lim discloses consulting for Philips, Venus, and Valgen and receiving research grants from Abbott, Boston Scientific, Edwards Lifesciences, and Medtronic. Dr. Koulogiannis discloses consulting and serving on an advisory board for Edwards Lifesciences and as a speaker for Abbott and discloses holding equity, stocks, or stock options in 4C. Dr. Thourani discloses serving as a consultant to both Abbott and Edwards Lifesciences. Dr. Young discloses receiving consulting fees or honoraria or serving on a speaker’s bureau for Medtronic. Dr. Asgar discloses receiving research support from or holding a research contract with Abbott Vascular and receiving consulting fees or honoraria or serving on a speaker’s bureau for Medtronic, Edwards Lifesciences, and W. Gore & Associates.

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

A newly available transcatheter device for edge-to-edge mitral valve (MV) repair, named for a famed scientist-inventor, is similar to the long-available MitraClip (Abbott) for short-term efficacy and safety, suggests an interim but prespecified analysis from a randomized trial.

In its comparison with MitraClip, the PASCAL transcatheter valve repair system (Edwards Lifesciences) was noninferior with respect to 30-day major adverse events and to success at achieving mitral regurgitation (MR) of no more than moderate severity within 6 months. The trial had entered patients with significant, symptomatic degenerative MR considered too high-risk for surgical repair or replacement.

The interim analysis covers 180 of the 300 patients followed in the study, of whom 117 received the PASCAL device and 63 were given MitraClip. Both groups showed significant gains in functional class, symptom status, and quality of life over 6 months, reported D. Scott Lim, MD, University of Virginia Health System Hospital, Charlottesville, and Konstantinos Koulogiannis, MD, Morristown Medical Center, N.J., jointly on Sept. 17 at the Transcatheter Cardiovascular Therapeutics (TCT) 2022 annual meeting in Boston.

Dr. Lim, one of the trial’s principal investigators, is also lead author on its same-day publication in JACC: Cardiovascular Interventions.

Based largely on those results from the CLASP IID pivotal trial, the U.S. Food and Drug Administration recently approved the PASCAL system for use in patients with degenerative MR, Edwards announced on Sept. 15. The device was approved in the European Union on Aug. 17.

MitraClip has been available in various iterations in the United States since 2013 and in Europe since 2008.

“It’s good for the field to be able to say we have two devices that are comparable,” giving clinicians more options, Vinod H. Thourani, MD, Piedmont Heart Institute, Atlanta, told this news organization.

The current analysis shows that “we’ve yet to figure out what patient pathologies will be beneficial” for each of the devices, Dr. Thourani said. “The goal will be to find out if there are certain anatomical considerations where one device is better than the other.”

It will be necessary to study “more patients, a larger cohort, with longer follow-up to allow us to see their true benefits,” he said, as well as to conduct more subgroup analyses. For now, the choice of device will probably be “operator-specific, which they feel comfortable with.”

Dr. Thourani, not an author on the current study, is the U.S. principal investigator for the CLASP IIF study looking at clinical outcomes with the two devices and says he consults for both Edwards and Abbott.

The findings are “preliminary for now,” said Michael Young, MD, Dartmouth-Hitchcock Medical Center, Lebanon, N.H., in part because, like most randomized trials, CLASP IID entered a select, not broadly representative population.

“They want to make, as best as they could, an apples-to-apples comparison, without confounding that might make it more difficult to interpret it afterwards,” Dr. Young, not associated with the trial, told this news organization.

But CLASP IID “did enroll patients that we do see and treat, so undoubtedly it’s a compelling study. We now have another device that is shown to be safe and effective. How we’re going to extrapolate it to all the patients that are being referred to our practices will, I think, be under debate and deliberation.”

The PASCAL and MitraClip devices each may be more suitable for different patients with varying mitral valve pathologies because of differences in their designs, Dr. Lim said. The PASCAL’s relative flexibility might make it preferable in patients with smaller mitral valves, and its ability to elongate during delivery could make it more suitable for patients with chordal-dense areas around the valve, he speculated.

MitraClip, Dr. Lim told this news organization, has a mechanical closure system for anchoring that may make it more appropriate for “more complicated, thicker leaflets with calcium.”

CLASP IID enrolled patients with grade 3+ or 4+ degenerative MR considered to be “at prohibitive surgical risk” at 43 sites in North America and Europe. It randomly assigned them 2-to-1 to receive the PASCAL device or MitraClip.

Either of two PASCAL versions were used, the original device or the “smaller, narrower” PASCAL Ace, Dr. Lim observed. Both versions are covered by the PASCAL Precision System FDA approval. About 40% of patients assigned to MitraClip received older versions of the device and about 60%, more recent versions, as they were entered into practice.

The mean procedure times were 88 minutes for PASCAL and 79 minutes for MitraClip (P = .023), with much of the difference attributable to the earliest PASCAL procedures. Procedure times for the device declined with greater operator experience, the published report states.

Rates of the primary safety endpoint of major adverse events at 30 days were 3.4% for PASCAL and 4.8% for MitraClip. The endpoint was a composite of cardiovascular  mortality, stroke, myocardial infarction, new need for renal replacement therapy, severe bleeding, or nonelective MV reintervention.

The proportion of patients with MR grade 2+ or lower at 6 months, the primary effectiveness endpoint, assessed at a core laboratory, was 96.5% for the PASCAL group over a median follow-up of 179.5 days and 96.8% over a median of 184.5 days for those who received MitraClip.

Comparisons for both primary endpoints met the prespecified criteria for PASCAL noninferiority.

In a secondary analysis, the proportion of PASCAL patients with MR grade 1+ or less held about steady from postprocedure discharge out to 6 months, at 87.2% and 83.7%, respectively (P = .317).

But  whereas 88.5% of MitraClip patients had MR grade 1+ or better at discharge, 71.2% were at that grade by 6 months (P = .003). That apparent hemodynamic deterioration raised some eyebrows at the TCT sessions as a potential sign that PASCAL functional results are more durable.

That sort of judgment is premature, offered Anita W. Asgar, MD, MSc, Montreal Heart Institute, Quebec City, as an invited discussant after the CLASP IID trial’s formal presentation at the meeting, which was sponsored by the Cardiovascular Research Foundation.

The trial is notable in part for “showing how safe this procedure is and how successful it is for these patients – this is phenomenal,” she said, but “I would caution comparing one device being better than another with such a small number of patients.”

MitraClip, Dr. Young observed, “has been, up to this point, our only option for edge-to-edge repair of the mitral valve. And many of us have years of experience and a lot of patients that we treat with that device.” His center hasn’t yet used PASCAL, but that may change as the field gains more familiarity with the device. Operators may use either device in different cases, he said.

“Depending on the program, and depending on the volume of mitral patients that you see and edge-to-edge repair that you do, it could be that you stick with one, or switch to another, or you integrate both of them and try to decide which patients might be better suited for one or the other.”

CLASP IID was sponsored by Edwards Lifesciences. Dr. Lim discloses consulting for Philips, Venus, and Valgen and receiving research grants from Abbott, Boston Scientific, Edwards Lifesciences, and Medtronic. Dr. Koulogiannis discloses consulting and serving on an advisory board for Edwards Lifesciences and as a speaker for Abbott and discloses holding equity, stocks, or stock options in 4C. Dr. Thourani discloses serving as a consultant to both Abbott and Edwards Lifesciences. Dr. Young discloses receiving consulting fees or honoraria or serving on a speaker’s bureau for Medtronic. Dr. Asgar discloses receiving research support from or holding a research contract with Abbott Vascular and receiving consulting fees or honoraria or serving on a speaker’s bureau for Medtronic, Edwards Lifesciences, and W. Gore & Associates.

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

A newly available transcatheter device for edge-to-edge mitral valve (MV) repair, named for a famed scientist-inventor, is similar to the long-available MitraClip (Abbott) for short-term efficacy and safety, suggests an interim but prespecified analysis from a randomized trial.

In its comparison with MitraClip, the PASCAL transcatheter valve repair system (Edwards Lifesciences) was noninferior with respect to 30-day major adverse events and to success at achieving mitral regurgitation (MR) of no more than moderate severity within 6 months. The trial had entered patients with significant, symptomatic degenerative MR considered too high-risk for surgical repair or replacement.

The interim analysis covers 180 of the 300 patients followed in the study, of whom 117 received the PASCAL device and 63 were given MitraClip. Both groups showed significant gains in functional class, symptom status, and quality of life over 6 months, reported D. Scott Lim, MD, University of Virginia Health System Hospital, Charlottesville, and Konstantinos Koulogiannis, MD, Morristown Medical Center, N.J., jointly on Sept. 17 at the Transcatheter Cardiovascular Therapeutics (TCT) 2022 annual meeting in Boston.

Dr. Lim, one of the trial’s principal investigators, is also lead author on its same-day publication in JACC: Cardiovascular Interventions.

Based largely on those results from the CLASP IID pivotal trial, the U.S. Food and Drug Administration recently approved the PASCAL system for use in patients with degenerative MR, Edwards announced on Sept. 15. The device was approved in the European Union on Aug. 17.

MitraClip has been available in various iterations in the United States since 2013 and in Europe since 2008.

“It’s good for the field to be able to say we have two devices that are comparable,” giving clinicians more options, Vinod H. Thourani, MD, Piedmont Heart Institute, Atlanta, told this news organization.

The current analysis shows that “we’ve yet to figure out what patient pathologies will be beneficial” for each of the devices, Dr. Thourani said. “The goal will be to find out if there are certain anatomical considerations where one device is better than the other.”

It will be necessary to study “more patients, a larger cohort, with longer follow-up to allow us to see their true benefits,” he said, as well as to conduct more subgroup analyses. For now, the choice of device will probably be “operator-specific, which they feel comfortable with.”

Dr. Thourani, not an author on the current study, is the U.S. principal investigator for the CLASP IIF study looking at clinical outcomes with the two devices and says he consults for both Edwards and Abbott.

The findings are “preliminary for now,” said Michael Young, MD, Dartmouth-Hitchcock Medical Center, Lebanon, N.H., in part because, like most randomized trials, CLASP IID entered a select, not broadly representative population.

“They want to make, as best as they could, an apples-to-apples comparison, without confounding that might make it more difficult to interpret it afterwards,” Dr. Young, not associated with the trial, told this news organization.

But CLASP IID “did enroll patients that we do see and treat, so undoubtedly it’s a compelling study. We now have another device that is shown to be safe and effective. How we’re going to extrapolate it to all the patients that are being referred to our practices will, I think, be under debate and deliberation.”

The PASCAL and MitraClip devices each may be more suitable for different patients with varying mitral valve pathologies because of differences in their designs, Dr. Lim said. The PASCAL’s relative flexibility might make it preferable in patients with smaller mitral valves, and its ability to elongate during delivery could make it more suitable for patients with chordal-dense areas around the valve, he speculated.

MitraClip, Dr. Lim told this news organization, has a mechanical closure system for anchoring that may make it more appropriate for “more complicated, thicker leaflets with calcium.”

CLASP IID enrolled patients with grade 3+ or 4+ degenerative MR considered to be “at prohibitive surgical risk” at 43 sites in North America and Europe. It randomly assigned them 2-to-1 to receive the PASCAL device or MitraClip.

Either of two PASCAL versions were used, the original device or the “smaller, narrower” PASCAL Ace, Dr. Lim observed. Both versions are covered by the PASCAL Precision System FDA approval. About 40% of patients assigned to MitraClip received older versions of the device and about 60%, more recent versions, as they were entered into practice.

The mean procedure times were 88 minutes for PASCAL and 79 minutes for MitraClip (P = .023), with much of the difference attributable to the earliest PASCAL procedures. Procedure times for the device declined with greater operator experience, the published report states.

Rates of the primary safety endpoint of major adverse events at 30 days were 3.4% for PASCAL and 4.8% for MitraClip. The endpoint was a composite of cardiovascular  mortality, stroke, myocardial infarction, new need for renal replacement therapy, severe bleeding, or nonelective MV reintervention.

The proportion of patients with MR grade 2+ or lower at 6 months, the primary effectiveness endpoint, assessed at a core laboratory, was 96.5% for the PASCAL group over a median follow-up of 179.5 days and 96.8% over a median of 184.5 days for those who received MitraClip.

Comparisons for both primary endpoints met the prespecified criteria for PASCAL noninferiority.

In a secondary analysis, the proportion of PASCAL patients with MR grade 1+ or less held about steady from postprocedure discharge out to 6 months, at 87.2% and 83.7%, respectively (P = .317).

But  whereas 88.5% of MitraClip patients had MR grade 1+ or better at discharge, 71.2% were at that grade by 6 months (P = .003). That apparent hemodynamic deterioration raised some eyebrows at the TCT sessions as a potential sign that PASCAL functional results are more durable.

That sort of judgment is premature, offered Anita W. Asgar, MD, MSc, Montreal Heart Institute, Quebec City, as an invited discussant after the CLASP IID trial’s formal presentation at the meeting, which was sponsored by the Cardiovascular Research Foundation.

The trial is notable in part for “showing how safe this procedure is and how successful it is for these patients – this is phenomenal,” she said, but “I would caution comparing one device being better than another with such a small number of patients.”

MitraClip, Dr. Young observed, “has been, up to this point, our only option for edge-to-edge repair of the mitral valve. And many of us have years of experience and a lot of patients that we treat with that device.” His center hasn’t yet used PASCAL, but that may change as the field gains more familiarity with the device. Operators may use either device in different cases, he said.

“Depending on the program, and depending on the volume of mitral patients that you see and edge-to-edge repair that you do, it could be that you stick with one, or switch to another, or you integrate both of them and try to decide which patients might be better suited for one or the other.”

CLASP IID was sponsored by Edwards Lifesciences. Dr. Lim discloses consulting for Philips, Venus, and Valgen and receiving research grants from Abbott, Boston Scientific, Edwards Lifesciences, and Medtronic. Dr. Koulogiannis discloses consulting and serving on an advisory board for Edwards Lifesciences and as a speaker for Abbott and discloses holding equity, stocks, or stock options in 4C. Dr. Thourani discloses serving as a consultant to both Abbott and Edwards Lifesciences. Dr. Young discloses receiving consulting fees or honoraria or serving on a speaker’s bureau for Medtronic. Dr. Asgar discloses receiving research support from or holding a research contract with Abbott Vascular and receiving consulting fees or honoraria or serving on a speaker’s bureau for Medtronic, Edwards Lifesciences, and W. Gore & Associates.

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

BARCELONA – Increased frailty of patients with heart failure with preserved ejection fraction (HFpEF) should have no bearing on whether those patients receive sacubitril/valsartan (Entresto), according to results of a post hoc analysis of data from a pivotal trial.

Plus, a recently reported prespecified analysis of data from a different pivotal trial shows that the same rule applies to patients with HFpEF who receive treatment with dapagliflozin (Farxiga). A pair of earlier reports showed similar findings for dapagliflozin and sacubitril/valsartan in patients with heart failure with reduced ejection fraction (HFrEF).

“There appears to be a greater reduction in the primary outcome and in hospitalizations for heart failure with sacubitril/valsartan compared with valsartan with increasing frailty, and sacubitril/valsartan was safe and well tolerated regardless of frailty status” in post hoc analysis of data from the PARAGON-HF trial, Jawad H. Butt, MD, reported at the annual congress of the European Society of Cardiology.

Analysis of the treatment effect by sacubitril/valsartan compared with valsartan in patients with HFpEF in PARAGON-HF showed that sacubitril/valsartan actually benefited patients more as their frailty increased when researchers applied frailty severity as a continuous variable. When they analyzed frailty’s effect by dividing the study cohort into three subgroups based on frailty severity – not frail, more frail, and most frail – the statistical analysis showed no significant heterogeneity of effect, although the point estimates for each subgroup showed by far the biggest benefit among the most frail patients. A safety analysis showed consistent safety of sacubitril/valsartan compared with valsartan across all three frailty subgroups, Dr. Butt reported.

Simultaneously with his report at the congress the results appeared online in the Journal of the American College of Cardiology.
 

Don’t withhold sacubitril/valsartan because of frailty

“We should not withhold [sacubitril/valsartan] treatment in patients perceived to be frail,” Dr. Butt declared in an interview. “There are no safety concerns, and no efficacy concerns,” although he cautioned that sacubitril/valsartan is not indicated for all patients with HFpEF. “If you believe that sacubitril/valsartan is indicated for a patient with HFpEF, do not withhold it just because of frailty,” said Dr. Butt, a cardiologist at Copenhagen University Hospital.

Dr. Butt went a step further and stressed, “I don’t think we should measure frailty” when considering patients with heart failure for treatment with sacubitril/valsartan, or with dapagliflozin, which had shown safety and maintained efficacy in a prespecified analysis he recently reported for patients with HFpEF, and in a separate recent report on a post hoc analysis of dapagliflozin use in patients with HFrEF in the DAPA-HF trial.

A published report also showed no evidence for an interaction between frailty and efficacy for sacubitril/valsartan compared with valsartan in the PARADIGM-HF pivotal trial, which enrolled people with HFrEF.

The issue of treatment safety and efficacy for patients considered frail is especially notable because “clinicians may be more reluctant to initiate new therapies due to doubt about the benefit of treatments in frail patients and apprehensions about predisposing them to potential new adverse effects,” said Dr. Butt.

“We should not defer these treatments on account of patient frailty,” said Maja Cikes, MD, a cardiologist at the University Hospital Center Zagreb, Croatia. The report by Dr. Butt “shows the safety” of using sacubitril/valsartan in most patients with HFpEF regardless of their frailty status, Dr. Cikes added in an interview.

Mitchel L. Zoler/MDedge News

‘Benefits without increasing the risk of frailty’

The data reported by Dr. Butt “suggest that although frail older persons with HFpEF are at greater risk for adverse outcomes overall, the prescription of sacubitril/valsartan seems to confer benefits without increasing the risk of frailty-related adverse events,” George A. Heckman, MD, a geriatrician at the University of Waterloo (Canada), and Kenneth Rockwood, MD, professor of geriatric medicine at Dalhousie University in Halifax, N.S., wrote in an editorial that accompanied the published version of Dr. Butt’s report.

The PARADIGM-HF trial enrolled 4,822 patients with heart failure and a left ventricular ejection fraction of at least 45% at 848 centers in 43 countries during 2014-2016, and followed them for a median of 35 months, with a primary endpoint of the combined rate of hospitalization for heart failure or cardiovascular death. Treatment with sacubitril/valsartan reduced the incidence of the primary endpoint by 13% compared with the control patients who received valsartan, a difference that missed narrowly missed significance (P = .06).

Despite this statistically neutral result, the Food and Drug Administration subsequently, based on these results, modified the indication for using sacubitril/valsartan from exclusively patients with HFrEF to patients with higher left ventricular ejection fractions, including at least some patients diagnosed with HFpEF.

To run the frailty analysis, Dr. Butt and his associates devised a 41-item frailty index, which identified 45% of the study cohort as not frail, 44% as more frail, and 11% as most frail. Their analyses also showed that frailty severity had no significant relationship to the effect of treatment with sacubitril valsartan on improving quality of life, or on improving functional status. Frailty also played no apparent role in the impact of sacubitril/valsartan compared with valsartan on treatment discontinuations or adverse effects.

PARAGON-HF and PARADIGM-HF were sponsored by Novartis, the company that markets sacubitril/valsartan (Entresto). Dr. Butt has been an adviser to Bayer. Dr. Cikes has received travel support or honoraria from Novartis as well as from Amicus, AstraZeneca, Bayer, Boehringer Ingelheim, GE Healthcare, Krka, LivaNova, Pfizer, Sanofi, and Teva, and research support or contracts from Novartis as well as from Abbott, Corvia, and Pfizer. Dr. Heckman had no disclosures. Dr. Rockwood is a cofounder of Ardea Outcomes, an adviser to Nutricia, and he holds a copyright through Dalhousie University on the Clinical Frailty Scale (which allows free use for educational, research, and not-for-profit health care purposes).

BARCELONA – Increased frailty of patients with heart failure with preserved ejection fraction (HFpEF) should have no bearing on whether those patients receive sacubitril/valsartan (Entresto), according to results of a post hoc analysis of data from a pivotal trial.

Plus, a recently reported prespecified analysis of data from a different pivotal trial shows that the same rule applies to patients with HFpEF who receive treatment with dapagliflozin (Farxiga). A pair of earlier reports showed similar findings for dapagliflozin and sacubitril/valsartan in patients with heart failure with reduced ejection fraction (HFrEF).

“There appears to be a greater reduction in the primary outcome and in hospitalizations for heart failure with sacubitril/valsartan compared with valsartan with increasing frailty, and sacubitril/valsartan was safe and well tolerated regardless of frailty status” in post hoc analysis of data from the PARAGON-HF trial, Jawad H. Butt, MD, reported at the annual congress of the European Society of Cardiology.

Analysis of the treatment effect by sacubitril/valsartan compared with valsartan in patients with HFpEF in PARAGON-HF showed that sacubitril/valsartan actually benefited patients more as their frailty increased when researchers applied frailty severity as a continuous variable. When they analyzed frailty’s effect by dividing the study cohort into three subgroups based on frailty severity – not frail, more frail, and most frail – the statistical analysis showed no significant heterogeneity of effect, although the point estimates for each subgroup showed by far the biggest benefit among the most frail patients. A safety analysis showed consistent safety of sacubitril/valsartan compared with valsartan across all three frailty subgroups, Dr. Butt reported.

Simultaneously with his report at the congress the results appeared online in the Journal of the American College of Cardiology.
 

Don’t withhold sacubitril/valsartan because of frailty

“We should not withhold [sacubitril/valsartan] treatment in patients perceived to be frail,” Dr. Butt declared in an interview. “There are no safety concerns, and no efficacy concerns,” although he cautioned that sacubitril/valsartan is not indicated for all patients with HFpEF. “If you believe that sacubitril/valsartan is indicated for a patient with HFpEF, do not withhold it just because of frailty,” said Dr. Butt, a cardiologist at Copenhagen University Hospital.

Dr. Butt went a step further and stressed, “I don’t think we should measure frailty” when considering patients with heart failure for treatment with sacubitril/valsartan, or with dapagliflozin, which had shown safety and maintained efficacy in a prespecified analysis he recently reported for patients with HFpEF, and in a separate recent report on a post hoc analysis of dapagliflozin use in patients with HFrEF in the DAPA-HF trial.

A published report also showed no evidence for an interaction between frailty and efficacy for sacubitril/valsartan compared with valsartan in the PARADIGM-HF pivotal trial, which enrolled people with HFrEF.

The issue of treatment safety and efficacy for patients considered frail is especially notable because “clinicians may be more reluctant to initiate new therapies due to doubt about the benefit of treatments in frail patients and apprehensions about predisposing them to potential new adverse effects,” said Dr. Butt.

“We should not defer these treatments on account of patient frailty,” said Maja Cikes, MD, a cardiologist at the University Hospital Center Zagreb, Croatia. The report by Dr. Butt “shows the safety” of using sacubitril/valsartan in most patients with HFpEF regardless of their frailty status, Dr. Cikes added in an interview.

Mitchel L. Zoler/MDedge News

‘Benefits without increasing the risk of frailty’

The data reported by Dr. Butt “suggest that although frail older persons with HFpEF are at greater risk for adverse outcomes overall, the prescription of sacubitril/valsartan seems to confer benefits without increasing the risk of frailty-related adverse events,” George A. Heckman, MD, a geriatrician at the University of Waterloo (Canada), and Kenneth Rockwood, MD, professor of geriatric medicine at Dalhousie University in Halifax, N.S., wrote in an editorial that accompanied the published version of Dr. Butt’s report.

The PARADIGM-HF trial enrolled 4,822 patients with heart failure and a left ventricular ejection fraction of at least 45% at 848 centers in 43 countries during 2014-2016, and followed them for a median of 35 months, with a primary endpoint of the combined rate of hospitalization for heart failure or cardiovascular death. Treatment with sacubitril/valsartan reduced the incidence of the primary endpoint by 13% compared with the control patients who received valsartan, a difference that missed narrowly missed significance (P = .06).

Despite this statistically neutral result, the Food and Drug Administration subsequently, based on these results, modified the indication for using sacubitril/valsartan from exclusively patients with HFrEF to patients with higher left ventricular ejection fractions, including at least some patients diagnosed with HFpEF.

To run the frailty analysis, Dr. Butt and his associates devised a 41-item frailty index, which identified 45% of the study cohort as not frail, 44% as more frail, and 11% as most frail. Their analyses also showed that frailty severity had no significant relationship to the effect of treatment with sacubitril valsartan on improving quality of life, or on improving functional status. Frailty also played no apparent role in the impact of sacubitril/valsartan compared with valsartan on treatment discontinuations or adverse effects.

PARAGON-HF and PARADIGM-HF were sponsored by Novartis, the company that markets sacubitril/valsartan (Entresto). Dr. Butt has been an adviser to Bayer. Dr. Cikes has received travel support or honoraria from Novartis as well as from Amicus, AstraZeneca, Bayer, Boehringer Ingelheim, GE Healthcare, Krka, LivaNova, Pfizer, Sanofi, and Teva, and research support or contracts from Novartis as well as from Abbott, Corvia, and Pfizer. Dr. Heckman had no disclosures. Dr. Rockwood is a cofounder of Ardea Outcomes, an adviser to Nutricia, and he holds a copyright through Dalhousie University on the Clinical Frailty Scale (which allows free use for educational, research, and not-for-profit health care purposes).

BARCELONA – Increased frailty of patients with heart failure with preserved ejection fraction (HFpEF) should have no bearing on whether those patients receive sacubitril/valsartan (Entresto), according to results of a post hoc analysis of data from a pivotal trial.

Plus, a recently reported prespecified analysis of data from a different pivotal trial shows that the same rule applies to patients with HFpEF who receive treatment with dapagliflozin (Farxiga). A pair of earlier reports showed similar findings for dapagliflozin and sacubitril/valsartan in patients with heart failure with reduced ejection fraction (HFrEF).

“There appears to be a greater reduction in the primary outcome and in hospitalizations for heart failure with sacubitril/valsartan compared with valsartan with increasing frailty, and sacubitril/valsartan was safe and well tolerated regardless of frailty status” in post hoc analysis of data from the PARAGON-HF trial, Jawad H. Butt, MD, reported at the annual congress of the European Society of Cardiology.

Analysis of the treatment effect by sacubitril/valsartan compared with valsartan in patients with HFpEF in PARAGON-HF showed that sacubitril/valsartan actually benefited patients more as their frailty increased when researchers applied frailty severity as a continuous variable. When they analyzed frailty’s effect by dividing the study cohort into three subgroups based on frailty severity – not frail, more frail, and most frail – the statistical analysis showed no significant heterogeneity of effect, although the point estimates for each subgroup showed by far the biggest benefit among the most frail patients. A safety analysis showed consistent safety of sacubitril/valsartan compared with valsartan across all three frailty subgroups, Dr. Butt reported.

Simultaneously with his report at the congress the results appeared online in the Journal of the American College of Cardiology.
 

Don’t withhold sacubitril/valsartan because of frailty

“We should not withhold [sacubitril/valsartan] treatment in patients perceived to be frail,” Dr. Butt declared in an interview. “There are no safety concerns, and no efficacy concerns,” although he cautioned that sacubitril/valsartan is not indicated for all patients with HFpEF. “If you believe that sacubitril/valsartan is indicated for a patient with HFpEF, do not withhold it just because of frailty,” said Dr. Butt, a cardiologist at Copenhagen University Hospital.

Dr. Butt went a step further and stressed, “I don’t think we should measure frailty” when considering patients with heart failure for treatment with sacubitril/valsartan, or with dapagliflozin, which had shown safety and maintained efficacy in a prespecified analysis he recently reported for patients with HFpEF, and in a separate recent report on a post hoc analysis of dapagliflozin use in patients with HFrEF in the DAPA-HF trial.

A published report also showed no evidence for an interaction between frailty and efficacy for sacubitril/valsartan compared with valsartan in the PARADIGM-HF pivotal trial, which enrolled people with HFrEF.

The issue of treatment safety and efficacy for patients considered frail is especially notable because “clinicians may be more reluctant to initiate new therapies due to doubt about the benefit of treatments in frail patients and apprehensions about predisposing them to potential new adverse effects,” said Dr. Butt.

“We should not defer these treatments on account of patient frailty,” said Maja Cikes, MD, a cardiologist at the University Hospital Center Zagreb, Croatia. The report by Dr. Butt “shows the safety” of using sacubitril/valsartan in most patients with HFpEF regardless of their frailty status, Dr. Cikes added in an interview.

Mitchel L. Zoler/MDedge News

‘Benefits without increasing the risk of frailty’

The data reported by Dr. Butt “suggest that although frail older persons with HFpEF are at greater risk for adverse outcomes overall, the prescription of sacubitril/valsartan seems to confer benefits without increasing the risk of frailty-related adverse events,” George A. Heckman, MD, a geriatrician at the University of Waterloo (Canada), and Kenneth Rockwood, MD, professor of geriatric medicine at Dalhousie University in Halifax, N.S., wrote in an editorial that accompanied the published version of Dr. Butt’s report.

The PARADIGM-HF trial enrolled 4,822 patients with heart failure and a left ventricular ejection fraction of at least 45% at 848 centers in 43 countries during 2014-2016, and followed them for a median of 35 months, with a primary endpoint of the combined rate of hospitalization for heart failure or cardiovascular death. Treatment with sacubitril/valsartan reduced the incidence of the primary endpoint by 13% compared with the control patients who received valsartan, a difference that missed narrowly missed significance (P = .06).

Despite this statistically neutral result, the Food and Drug Administration subsequently, based on these results, modified the indication for using sacubitril/valsartan from exclusively patients with HFrEF to patients with higher left ventricular ejection fractions, including at least some patients diagnosed with HFpEF.

To run the frailty analysis, Dr. Butt and his associates devised a 41-item frailty index, which identified 45% of the study cohort as not frail, 44% as more frail, and 11% as most frail. Their analyses also showed that frailty severity had no significant relationship to the effect of treatment with sacubitril valsartan on improving quality of life, or on improving functional status. Frailty also played no apparent role in the impact of sacubitril/valsartan compared with valsartan on treatment discontinuations or adverse effects.

PARAGON-HF and PARADIGM-HF were sponsored by Novartis, the company that markets sacubitril/valsartan (Entresto). Dr. Butt has been an adviser to Bayer. Dr. Cikes has received travel support or honoraria from Novartis as well as from Amicus, AstraZeneca, Bayer, Boehringer Ingelheim, GE Healthcare, Krka, LivaNova, Pfizer, Sanofi, and Teva, and research support or contracts from Novartis as well as from Abbott, Corvia, and Pfizer. Dr. Heckman had no disclosures. Dr. Rockwood is a cofounder of Ardea Outcomes, an adviser to Nutricia, and he holds a copyright through Dalhousie University on the Clinical Frailty Scale (which allows free use for educational, research, and not-for-profit health care purposes).

Treatment of people with obesity but without diabetes with the glucagon-like peptide-1 (GLP-1) agonist semaglutide (Wegovy) – hailed at its approval in 2021 as a “game changer” for the treatment of obesity – led to beneficial changes in body mass index (BMI), glycemic control, and other clinical measures.

This collectively cut the calculated risk for possible future development of type 2 diabetes in study participants by more than half, based on post-hoc analysis of data from two pivotal trials that compared semaglutide with placebo.

The findings “suggest that semaglutide could help prevent type 2 diabetes in people with overweight or obesity,” said W. Timothy Garvey, MD, in a presentation at the annual meeting of the European Association for the Study of Diabetes.

Asked to comment, Rodolfo J. Galindo, MD, said: “We devote a significant amount of effort to treating people with diabetes but very little effort for diabetes prevention. We hope that further scientific findings showing the benefits of weight loss, as illustrated by [Dr.] Garvey [and colleagues], for diabetes prevention will change the pandemic of adiposity-based chronic disease.”
 

GLP-1 agonists as complication-reducing agents

Finding a link between treatment with semaglutide and a reduced future risk of developing type 2 diabetes is important because it shows that this regimen is not just a BMI-centric approach to treating people with obesity but is also a way to potentially reduce complications of obesity such as diabetes onset, explained Dr. Garvey, a professor and director of the Diabetes Research Center at the University of Alabama at Birmingham.

Recent obesity-management recommendations have focused on interventions aimed at avoiding complications, as in 2016 guidelines from the American Association of Clinical Endocrinologists and the American College of Endocrinology, he noted.

Having evidence that treatment with a GLP-1 agonist such as semaglutide can reduce the incidence of diabetes in people with obesity might also help convince payers to more uniformly reimburse for this type of obesity intervention, which up to now has commonly faced coverage limitations, especially in the United States, he said in an interview.

Dr. Garvey added that evidence for a reduction in the incidence of cardiovascular disease complications such as myocardial infarction and stroke may need to join diabetes prevention as proven effects from obesity intervention before coverage decisions change.

He cited the SELECT trial, which is testing the hypothesis that semaglutide treatment of people with overweight or obesity can reduce the incidence of cardiovascular events in about 17,500 participants and with expected completion toward the end of 2023.

“A complication-centric approach to management of people with obesity needs prediction tools that allow a focus on prevention strategies for people with obesity who are at increased risk of developing diabetes,” commented Dr. Galindo, an endocrinologist at Emory University, Atlanta, in an interview.
 

Combined analysis of STEP 1 and STEP 4 data

The analysis conducted by Dr. Garvey and colleagues used data from the STEP 1 trial, which compared semaglutide 2.4 mg subcutaneous once weekly with placebo for weight loss in more than 1,500 people predominantly with obesity (about 6% were overweight) and showed that after 68 weeks semaglutide cut the calculated risk of developing type 2 diabetes over the subsequent 10 years from 18% at baseline to 7%, compared with a drop from 18% at baseline to 16% among those who received placebo.

A second, similar analysis of data from people predominantly with obesity in the STEP 4 trial – which treated around 800 people with semaglutide 2.4 mg for 20 weeks and then randomized them to placebo or continued semaglutide treatment – showed that semaglutide treatment cut their calculated 10-year risk for incident type 2 diabetes from 20% at baseline to about 11% after 20 weeks. The risk rebounded in the study participants who then switched from semaglutide to placebo. Among those randomized to remain on semaglutide for a total of 68 weeks, the 10-year risk fell further to 8%.

Dr. Garvey and associates used a validated prognostic formula, the cardiometabolic disease staging (CMDS) tool, they had previously developed and reported to calculate 10-year risk for development of type 2 diabetes based on three unmodifiable factors (age, sex, and race) and five modifiable factors (BMI, blood pressure, glucose level, HDL cholesterol, and triglycerides). They applied the analysis to data from 1,561 of the STEP 1 participants and 766 participants in the STEP 4 study.

“There is no better tool I know of to predict diabetes incidence,” commented Michael A. Nauck, MD, professor and chief of clinical research, diabetes division, St. Josef Hospital, Bochum, Germany.

In his opinion, the CMDS tool is appropriate for estimating the risk of developing incident type 2 diabetes in populations but not in specific individuals.

The new analyses also showed that, in STEP 1, the impact of semaglutide on reducing future risk of developing type 2 diabetes was roughly the same regardless of whether participants entered the study with prediabetes or were normoglycemic at entry.

Blood glucose changes confer the biggest effect

The biggest contributor among the five modifiable components of the CMDS tool for altering the predicted risk for incident diabetes was the reduction in blood glucose produced by semaglutide treatment, which influenced just under half of the change in predicted risk, Dr. Garvey said. The four other modifiable components had roughly similar individual effects on predicted risk, with change in BMI influencing about 15% of the observed effect.

“Our analysis shows that semaglutide treatment is preventing diabetes via several mechanisms. It’s not just a reduction in glucose,” Dr. Garvey said.

Dr. Nauck cautioned, however, that it is hard to judge the efficacy of an intervention like semaglutide for preventing incident diabetes when one of its effects is to dampen down hyperglycemia, the signal indicator of diabetes onset.

Indeed, semaglutide was first approved as a treatment for type 2 diabetes (known as Ozempic, Novo Nordisk) at slightly lower doses than it is approved for obesity. It is also available as an oral agent to treat diabetes (Rybelsus).  

Dr. Nauck also noted that the results from at least one previously reported study had already shown the same relationship between treatment with the GLP-1 agonist liraglutide as an anti-obesity agent (3.0 mg dose daily, known as Saxenda) and a reduced subsequent incidence of type 2 diabetes but using actual clinical outcomes during 3 years of follow-up rather than a calculated projection of diabetes likelihood.

The SCALE Obesity and Prediabetes trial randomized 2,254 people with prediabetes and overweight or obesity to weekly treatment with 3.0 mg of liraglutide or placebo. After 160 weeks on treatment, the cumulative incidence of type 2 diabetes was 2% in those who received liraglutide and 6% among those on placebo, with a significant hazard ratio reduction of 79% in the incidence of diabetes on liraglutide treatment.

The STEP 1 and STEP 4 trials were sponsored by Novo Nordisk, the company that markets semaglutide (Wegovy). Dr. Garvey has reported serving as an advisor without compensation to Novo Nordisk as well as Boehringer Ingelheim, Eli Lilly, Jazz, and Pfizer. He is also a site principal investigator for multicentered clinical trials sponsored by the University of Alabama at Birmingham and funded by Novo Nordisk, Eli Lilly, Epitomee, and Pfizer. Dr .Galindo has reported being a consultant or advisor for Boehringer Ingelheim, Eli Lilly, Pfizer, Sanofi, and Weight Watchers and receiving research funding from Dexcom, Eli Lilly, and Novo Nordisk. Dr. Nauck has reported being an advisor or consultant to Novo Nordisk as well as to Boehringer Ingelheim, Eli Lilly, Menarini/Berlin Chemie, MSD, Regor, and ShouTi/Gasherbrum, receiving research funding from MSD, being a member of a data monitoring and safety board for Inventiva, and being a speaker on behalf of Novo Nordisk as well as for Eli Lilly, Menarini/Berlin Chemie, MSD, and Sun Pharmaceuticals.

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

Treatment of people with obesity but without diabetes with the glucagon-like peptide-1 (GLP-1) agonist semaglutide (Wegovy) – hailed at its approval in 2021 as a “game changer” for the treatment of obesity – led to beneficial changes in body mass index (BMI), glycemic control, and other clinical measures.

This collectively cut the calculated risk for possible future development of type 2 diabetes in study participants by more than half, based on post-hoc analysis of data from two pivotal trials that compared semaglutide with placebo.

The findings “suggest that semaglutide could help prevent type 2 diabetes in people with overweight or obesity,” said W. Timothy Garvey, MD, in a presentation at the annual meeting of the European Association for the Study of Diabetes.

Asked to comment, Rodolfo J. Galindo, MD, said: “We devote a significant amount of effort to treating people with diabetes but very little effort for diabetes prevention. We hope that further scientific findings showing the benefits of weight loss, as illustrated by [Dr.] Garvey [and colleagues], for diabetes prevention will change the pandemic of adiposity-based chronic disease.”
 

GLP-1 agonists as complication-reducing agents

Finding a link between treatment with semaglutide and a reduced future risk of developing type 2 diabetes is important because it shows that this regimen is not just a BMI-centric approach to treating people with obesity but is also a way to potentially reduce complications of obesity such as diabetes onset, explained Dr. Garvey, a professor and director of the Diabetes Research Center at the University of Alabama at Birmingham.

Recent obesity-management recommendations have focused on interventions aimed at avoiding complications, as in 2016 guidelines from the American Association of Clinical Endocrinologists and the American College of Endocrinology, he noted.

Having evidence that treatment with a GLP-1 agonist such as semaglutide can reduce the incidence of diabetes in people with obesity might also help convince payers to more uniformly reimburse for this type of obesity intervention, which up to now has commonly faced coverage limitations, especially in the United States, he said in an interview.

Dr. Garvey added that evidence for a reduction in the incidence of cardiovascular disease complications such as myocardial infarction and stroke may need to join diabetes prevention as proven effects from obesity intervention before coverage decisions change.

He cited the SELECT trial, which is testing the hypothesis that semaglutide treatment of people with overweight or obesity can reduce the incidence of cardiovascular events in about 17,500 participants and with expected completion toward the end of 2023.

“A complication-centric approach to management of people with obesity needs prediction tools that allow a focus on prevention strategies for people with obesity who are at increased risk of developing diabetes,” commented Dr. Galindo, an endocrinologist at Emory University, Atlanta, in an interview.
 

Combined analysis of STEP 1 and STEP 4 data

The analysis conducted by Dr. Garvey and colleagues used data from the STEP 1 trial, which compared semaglutide 2.4 mg subcutaneous once weekly with placebo for weight loss in more than 1,500 people predominantly with obesity (about 6% were overweight) and showed that after 68 weeks semaglutide cut the calculated risk of developing type 2 diabetes over the subsequent 10 years from 18% at baseline to 7%, compared with a drop from 18% at baseline to 16% among those who received placebo.

A second, similar analysis of data from people predominantly with obesity in the STEP 4 trial – which treated around 800 people with semaglutide 2.4 mg for 20 weeks and then randomized them to placebo or continued semaglutide treatment – showed that semaglutide treatment cut their calculated 10-year risk for incident type 2 diabetes from 20% at baseline to about 11% after 20 weeks. The risk rebounded in the study participants who then switched from semaglutide to placebo. Among those randomized to remain on semaglutide for a total of 68 weeks, the 10-year risk fell further to 8%.

Dr. Garvey and associates used a validated prognostic formula, the cardiometabolic disease staging (CMDS) tool, they had previously developed and reported to calculate 10-year risk for development of type 2 diabetes based on three unmodifiable factors (age, sex, and race) and five modifiable factors (BMI, blood pressure, glucose level, HDL cholesterol, and triglycerides). They applied the analysis to data from 1,561 of the STEP 1 participants and 766 participants in the STEP 4 study.

“There is no better tool I know of to predict diabetes incidence,” commented Michael A. Nauck, MD, professor and chief of clinical research, diabetes division, St. Josef Hospital, Bochum, Germany.

In his opinion, the CMDS tool is appropriate for estimating the risk of developing incident type 2 diabetes in populations but not in specific individuals.

The new analyses also showed that, in STEP 1, the impact of semaglutide on reducing future risk of developing type 2 diabetes was roughly the same regardless of whether participants entered the study with prediabetes or were normoglycemic at entry.

Blood glucose changes confer the biggest effect

The biggest contributor among the five modifiable components of the CMDS tool for altering the predicted risk for incident diabetes was the reduction in blood glucose produced by semaglutide treatment, which influenced just under half of the change in predicted risk, Dr. Garvey said. The four other modifiable components had roughly similar individual effects on predicted risk, with change in BMI influencing about 15% of the observed effect.

“Our analysis shows that semaglutide treatment is preventing diabetes via several mechanisms. It’s not just a reduction in glucose,” Dr. Garvey said.

Dr. Nauck cautioned, however, that it is hard to judge the efficacy of an intervention like semaglutide for preventing incident diabetes when one of its effects is to dampen down hyperglycemia, the signal indicator of diabetes onset.

Indeed, semaglutide was first approved as a treatment for type 2 diabetes (known as Ozempic, Novo Nordisk) at slightly lower doses than it is approved for obesity. It is also available as an oral agent to treat diabetes (Rybelsus).  

Dr. Nauck also noted that the results from at least one previously reported study had already shown the same relationship between treatment with the GLP-1 agonist liraglutide as an anti-obesity agent (3.0 mg dose daily, known as Saxenda) and a reduced subsequent incidence of type 2 diabetes but using actual clinical outcomes during 3 years of follow-up rather than a calculated projection of diabetes likelihood.

The SCALE Obesity and Prediabetes trial randomized 2,254 people with prediabetes and overweight or obesity to weekly treatment with 3.0 mg of liraglutide or placebo. After 160 weeks on treatment, the cumulative incidence of type 2 diabetes was 2% in those who received liraglutide and 6% among those on placebo, with a significant hazard ratio reduction of 79% in the incidence of diabetes on liraglutide treatment.

The STEP 1 and STEP 4 trials were sponsored by Novo Nordisk, the company that markets semaglutide (Wegovy). Dr. Garvey has reported serving as an advisor without compensation to Novo Nordisk as well as Boehringer Ingelheim, Eli Lilly, Jazz, and Pfizer. He is also a site principal investigator for multicentered clinical trials sponsored by the University of Alabama at Birmingham and funded by Novo Nordisk, Eli Lilly, Epitomee, and Pfizer. Dr .Galindo has reported being a consultant or advisor for Boehringer Ingelheim, Eli Lilly, Pfizer, Sanofi, and Weight Watchers and receiving research funding from Dexcom, Eli Lilly, and Novo Nordisk. Dr. Nauck has reported being an advisor or consultant to Novo Nordisk as well as to Boehringer Ingelheim, Eli Lilly, Menarini/Berlin Chemie, MSD, Regor, and ShouTi/Gasherbrum, receiving research funding from MSD, being a member of a data monitoring and safety board for Inventiva, and being a speaker on behalf of Novo Nordisk as well as for Eli Lilly, Menarini/Berlin Chemie, MSD, and Sun Pharmaceuticals.

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

Treatment of people with obesity but without diabetes with the glucagon-like peptide-1 (GLP-1) agonist semaglutide (Wegovy) – hailed at its approval in 2021 as a “game changer” for the treatment of obesity – led to beneficial changes in body mass index (BMI), glycemic control, and other clinical measures.

This collectively cut the calculated risk for possible future development of type 2 diabetes in study participants by more than half, based on post-hoc analysis of data from two pivotal trials that compared semaglutide with placebo.

The findings “suggest that semaglutide could help prevent type 2 diabetes in people with overweight or obesity,” said W. Timothy Garvey, MD, in a presentation at the annual meeting of the European Association for the Study of Diabetes.

Asked to comment, Rodolfo J. Galindo, MD, said: “We devote a significant amount of effort to treating people with diabetes but very little effort for diabetes prevention. We hope that further scientific findings showing the benefits of weight loss, as illustrated by [Dr.] Garvey [and colleagues], for diabetes prevention will change the pandemic of adiposity-based chronic disease.”
 

GLP-1 agonists as complication-reducing agents

Finding a link between treatment with semaglutide and a reduced future risk of developing type 2 diabetes is important because it shows that this regimen is not just a BMI-centric approach to treating people with obesity but is also a way to potentially reduce complications of obesity such as diabetes onset, explained Dr. Garvey, a professor and director of the Diabetes Research Center at the University of Alabama at Birmingham.

Recent obesity-management recommendations have focused on interventions aimed at avoiding complications, as in 2016 guidelines from the American Association of Clinical Endocrinologists and the American College of Endocrinology, he noted.

Having evidence that treatment with a GLP-1 agonist such as semaglutide can reduce the incidence of diabetes in people with obesity might also help convince payers to more uniformly reimburse for this type of obesity intervention, which up to now has commonly faced coverage limitations, especially in the United States, he said in an interview.

Dr. Garvey added that evidence for a reduction in the incidence of cardiovascular disease complications such as myocardial infarction and stroke may need to join diabetes prevention as proven effects from obesity intervention before coverage decisions change.

He cited the SELECT trial, which is testing the hypothesis that semaglutide treatment of people with overweight or obesity can reduce the incidence of cardiovascular events in about 17,500 participants and with expected completion toward the end of 2023.

“A complication-centric approach to management of people with obesity needs prediction tools that allow a focus on prevention strategies for people with obesity who are at increased risk of developing diabetes,” commented Dr. Galindo, an endocrinologist at Emory University, Atlanta, in an interview.
 

Combined analysis of STEP 1 and STEP 4 data

The analysis conducted by Dr. Garvey and colleagues used data from the STEP 1 trial, which compared semaglutide 2.4 mg subcutaneous once weekly with placebo for weight loss in more than 1,500 people predominantly with obesity (about 6% were overweight) and showed that after 68 weeks semaglutide cut the calculated risk of developing type 2 diabetes over the subsequent 10 years from 18% at baseline to 7%, compared with a drop from 18% at baseline to 16% among those who received placebo.

A second, similar analysis of data from people predominantly with obesity in the STEP 4 trial – which treated around 800 people with semaglutide 2.4 mg for 20 weeks and then randomized them to placebo or continued semaglutide treatment – showed that semaglutide treatment cut their calculated 10-year risk for incident type 2 diabetes from 20% at baseline to about 11% after 20 weeks. The risk rebounded in the study participants who then switched from semaglutide to placebo. Among those randomized to remain on semaglutide for a total of 68 weeks, the 10-year risk fell further to 8%.

Dr. Garvey and associates used a validated prognostic formula, the cardiometabolic disease staging (CMDS) tool, they had previously developed and reported to calculate 10-year risk for development of type 2 diabetes based on three unmodifiable factors (age, sex, and race) and five modifiable factors (BMI, blood pressure, glucose level, HDL cholesterol, and triglycerides). They applied the analysis to data from 1,561 of the STEP 1 participants and 766 participants in the STEP 4 study.

“There is no better tool I know of to predict diabetes incidence,” commented Michael A. Nauck, MD, professor and chief of clinical research, diabetes division, St. Josef Hospital, Bochum, Germany.

In his opinion, the CMDS tool is appropriate for estimating the risk of developing incident type 2 diabetes in populations but not in specific individuals.

The new analyses also showed that, in STEP 1, the impact of semaglutide on reducing future risk of developing type 2 diabetes was roughly the same regardless of whether participants entered the study with prediabetes or were normoglycemic at entry.

Blood glucose changes confer the biggest effect

The biggest contributor among the five modifiable components of the CMDS tool for altering the predicted risk for incident diabetes was the reduction in blood glucose produced by semaglutide treatment, which influenced just under half of the change in predicted risk, Dr. Garvey said. The four other modifiable components had roughly similar individual effects on predicted risk, with change in BMI influencing about 15% of the observed effect.

“Our analysis shows that semaglutide treatment is preventing diabetes via several mechanisms. It’s not just a reduction in glucose,” Dr. Garvey said.

Dr. Nauck cautioned, however, that it is hard to judge the efficacy of an intervention like semaglutide for preventing incident diabetes when one of its effects is to dampen down hyperglycemia, the signal indicator of diabetes onset.

Indeed, semaglutide was first approved as a treatment for type 2 diabetes (known as Ozempic, Novo Nordisk) at slightly lower doses than it is approved for obesity. It is also available as an oral agent to treat diabetes (Rybelsus).  

Dr. Nauck also noted that the results from at least one previously reported study had already shown the same relationship between treatment with the GLP-1 agonist liraglutide as an anti-obesity agent (3.0 mg dose daily, known as Saxenda) and a reduced subsequent incidence of type 2 diabetes but using actual clinical outcomes during 3 years of follow-up rather than a calculated projection of diabetes likelihood.

The SCALE Obesity and Prediabetes trial randomized 2,254 people with prediabetes and overweight or obesity to weekly treatment with 3.0 mg of liraglutide or placebo. After 160 weeks on treatment, the cumulative incidence of type 2 diabetes was 2% in those who received liraglutide and 6% among those on placebo, with a significant hazard ratio reduction of 79% in the incidence of diabetes on liraglutide treatment.

The STEP 1 and STEP 4 trials were sponsored by Novo Nordisk, the company that markets semaglutide (Wegovy). Dr. Garvey has reported serving as an advisor without compensation to Novo Nordisk as well as Boehringer Ingelheim, Eli Lilly, Jazz, and Pfizer. He is also a site principal investigator for multicentered clinical trials sponsored by the University of Alabama at Birmingham and funded by Novo Nordisk, Eli Lilly, Epitomee, and Pfizer. Dr .Galindo has reported being a consultant or advisor for Boehringer Ingelheim, Eli Lilly, Pfizer, Sanofi, and Weight Watchers and receiving research funding from Dexcom, Eli Lilly, and Novo Nordisk. Dr. Nauck has reported being an advisor or consultant to Novo Nordisk as well as to Boehringer Ingelheim, Eli Lilly, Menarini/Berlin Chemie, MSD, Regor, and ShouTi/Gasherbrum, receiving research funding from MSD, being a member of a data monitoring and safety board for Inventiva, and being a speaker on behalf of Novo Nordisk as well as for Eli Lilly, Menarini/Berlin Chemie, MSD, and Sun Pharmaceuticals.

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

Wearing a cuffless device on the wrist to continuously monitor blood pressure was associated with a significantly lower systolic BP at 6 months among hypertensive adults, real-world results from Europe show.

“We don’t know what they did to reduce their blood pressure,” Jay Shah, MD, Division of Cardiology, Mayo Clinic Arizona, Phoenix, told this news organization.

“The idea is that because they were exposed to their data on a continual basis, that may have prompted them to do something that led to an improvement in their blood pressure, whether it be exercise more, go to their doctor, or change their medication,” said Dr. Shah, who is also chief medical officer for Aktiia.

Dr. Shah presented the study at the Hypertension Scientific Sessions, San Diego.
 

Empowering data

The study used the Aktiia 24/7 BP monitor; Atkiia funded the trial. The monitor passively and continually monitors BP values from photoplethysmography signals collected via optical sensors at the wrist.

After initial individualized calibration using a cuff-based reference, BP measurements are displayed on a smartphone app, allowing users to consistently monitor their own BP for long periods of time.

Aktiia received CE mark in Europe in January 2021 and is currently under review by the U.S. Food and Drug Administration.

Dr. Shah and colleagues analyzed systolic BP (SBP) trends among 838 real-world Aktiia users in Europe (age 57 ± 11 years; 14% women) who consistently used the monitor for 6 months.

Altogether, they had data on 375 (± 287) app interactions, 3,646 (± 1,417) cuffless readings per user, and 9 (± 7) cuff readings per user.

Traditional cuff SBP averages were calculated monthly and compared with the SBP average of the first month. A t-test analysis was used to detect the difference in SBP between the first and successive months.

On the basis of the mean SBP calculated over 6 months, 136 participants were hypertensive (SBP > 140 mm Hg) and the rest had SBP less than 140 mm Hg.

Hypertensive users saw a statistically significant reduction in SBP of –3.2 mm Hg (95% CI, –0.70 to –5.59; P < .02), beginning at 3 months of continual cuffless BP monitoring, which was sustained through 6 months.

Among users with SBP less than 140 mm Hg, the mean SBP remained unchanged.

“The magnitude of improvement might look modest, but even a 5 mm Hg reduction in systolic BP correlates to a 10% decrease in cardiovascular risk,” Dr. Shah told this news organization.

He noted that “one of the major hurdles is that people may not be aware they have high blood pressure because they don’t feel it. And with a regular cuff, they’ll only see that number when they actually check their blood pressure, which is extremely rare, even for people who have hypertension.”

“Having the ability to show someone their continual blood pressure picture really empowers them to do something to make changes and to be aware, [as well as] to be a more active participant in their health,” Dr. Shah said.

He said that a good analogy is diabetes management, which has transitioned from single finger-stick glucose monitoring to continuous glucose monitoring that provides a complete 24/7 picture of glucose levels.

Transforming technology

Offering perspective on the study, Harlan Krumholz, MD, SM, with Yale New Haven Hospital and Yale School of Medicine, New Haven, Conn., said that having an accurate, affordable, unobtrusive cuffless continuous BP monitor would “transform” BP management.

Courtesy Yale University

“This could unlock an era of precision BP management with empowerment of patients to view and act on their numbers,” Dr. Krumholz said in an interview.

“We need data to be confident in the devices – and then research to best leverage the streams of information – and strategies to optimize its use in practice,” Dr. Krumholz added.

“Like any new innovation, we need to mitigate risks and monitor for unintended adverse consequences, but I am bullish on the future of cuffless continuous BP monitors,” Dr. Krumholz said.

Dr. Krumholz said that he “applauds Aktiia for doing studies that assess the effect of the information they are producing on BP over time. We need to know that new approaches not only generate valid information but that they can improve health.”
 

Ready for prime time?

In June, the European Society of Hypertension issued a statement noting that cuffless BP measurement is a fast-growing and promising field with considerable potential for improving hypertension awareness, management, and control, but because the accuracy of these new devices has not yet been validated, they are not yet suitable for clinical use.

Also providing perspective, Stephen Juraschek, MD, PhD, research director, Hypertension Center of Excellence at Healthcare Associates, Beth Israel Deaconess Medical Center, Boston, said that “there is a lot of interest in cuffless BP monitors due to their ease of measurement, comfort, and ability to obtain BP measurements in multiple settings and environments, and this study showed that the monitoring improved BP over time.”

“It is believed that the increased awareness and feedback may promote healthier behaviors aimed at lowering BP. However, this result should not be conflated with the accuracy of these monitors,” Dr. Juraschek cautioned.

He also noted that there is still no formally approved validation protocol by the Association for the Advancement of Medical Instrumentation.

“While a number of cuffless devices are cleared by the FDA through its 510k mechanism (that is, demonstration of device equivalence), there is no formal stamp of approval or attestation that the measurements are accurate,” Dr. Juraschek said in an interview.

In his view, “more work is needed to understand the validity of these devices. For now, validated, cuff-based home devices are recommended for BP measurement at home, while further work is done to determine the accuracy of these cuffless technologies.”

The study was funded by Aktiia. Dr. Shah is an employee of the company. Dr. Krumholz has no relevant disclosures. Dr. Juraschek is a member of the Validate BP review committee and the AAMI sphygmomanometer committee.

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

Wearing a cuffless device on the wrist to continuously monitor blood pressure was associated with a significantly lower systolic BP at 6 months among hypertensive adults, real-world results from Europe show.

“We don’t know what they did to reduce their blood pressure,” Jay Shah, MD, Division of Cardiology, Mayo Clinic Arizona, Phoenix, told this news organization.

“The idea is that because they were exposed to their data on a continual basis, that may have prompted them to do something that led to an improvement in their blood pressure, whether it be exercise more, go to their doctor, or change their medication,” said Dr. Shah, who is also chief medical officer for Aktiia.

Dr. Shah presented the study at the Hypertension Scientific Sessions, San Diego.
 

Empowering data

The study used the Aktiia 24/7 BP monitor; Atkiia funded the trial. The monitor passively and continually monitors BP values from photoplethysmography signals collected via optical sensors at the wrist.

After initial individualized calibration using a cuff-based reference, BP measurements are displayed on a smartphone app, allowing users to consistently monitor their own BP for long periods of time.

Aktiia received CE mark in Europe in January 2021 and is currently under review by the U.S. Food and Drug Administration.

Dr. Shah and colleagues analyzed systolic BP (SBP) trends among 838 real-world Aktiia users in Europe (age 57 ± 11 years; 14% women) who consistently used the monitor for 6 months.

Altogether, they had data on 375 (± 287) app interactions, 3,646 (± 1,417) cuffless readings per user, and 9 (± 7) cuff readings per user.

Traditional cuff SBP averages were calculated monthly and compared with the SBP average of the first month. A t-test analysis was used to detect the difference in SBP between the first and successive months.

On the basis of the mean SBP calculated over 6 months, 136 participants were hypertensive (SBP > 140 mm Hg) and the rest had SBP less than 140 mm Hg.

Hypertensive users saw a statistically significant reduction in SBP of –3.2 mm Hg (95% CI, –0.70 to –5.59; P < .02), beginning at 3 months of continual cuffless BP monitoring, which was sustained through 6 months.

Among users with SBP less than 140 mm Hg, the mean SBP remained unchanged.

“The magnitude of improvement might look modest, but even a 5 mm Hg reduction in systolic BP correlates to a 10% decrease in cardiovascular risk,” Dr. Shah told this news organization.

He noted that “one of the major hurdles is that people may not be aware they have high blood pressure because they don’t feel it. And with a regular cuff, they’ll only see that number when they actually check their blood pressure, which is extremely rare, even for people who have hypertension.”

“Having the ability to show someone their continual blood pressure picture really empowers them to do something to make changes and to be aware, [as well as] to be a more active participant in their health,” Dr. Shah said.

He said that a good analogy is diabetes management, which has transitioned from single finger-stick glucose monitoring to continuous glucose monitoring that provides a complete 24/7 picture of glucose levels.

Transforming technology

Offering perspective on the study, Harlan Krumholz, MD, SM, with Yale New Haven Hospital and Yale School of Medicine, New Haven, Conn., said that having an accurate, affordable, unobtrusive cuffless continuous BP monitor would “transform” BP management.

Courtesy Yale University

“This could unlock an era of precision BP management with empowerment of patients to view and act on their numbers,” Dr. Krumholz said in an interview.

“We need data to be confident in the devices – and then research to best leverage the streams of information – and strategies to optimize its use in practice,” Dr. Krumholz added.

“Like any new innovation, we need to mitigate risks and monitor for unintended adverse consequences, but I am bullish on the future of cuffless continuous BP monitors,” Dr. Krumholz said.

Dr. Krumholz said that he “applauds Aktiia for doing studies that assess the effect of the information they are producing on BP over time. We need to know that new approaches not only generate valid information but that they can improve health.”
 

Ready for prime time?

In June, the European Society of Hypertension issued a statement noting that cuffless BP measurement is a fast-growing and promising field with considerable potential for improving hypertension awareness, management, and control, but because the accuracy of these new devices has not yet been validated, they are not yet suitable for clinical use.

Also providing perspective, Stephen Juraschek, MD, PhD, research director, Hypertension Center of Excellence at Healthcare Associates, Beth Israel Deaconess Medical Center, Boston, said that “there is a lot of interest in cuffless BP monitors due to their ease of measurement, comfort, and ability to obtain BP measurements in multiple settings and environments, and this study showed that the monitoring improved BP over time.”

“It is believed that the increased awareness and feedback may promote healthier behaviors aimed at lowering BP. However, this result should not be conflated with the accuracy of these monitors,” Dr. Juraschek cautioned.

He also noted that there is still no formally approved validation protocol by the Association for the Advancement of Medical Instrumentation.

“While a number of cuffless devices are cleared by the FDA through its 510k mechanism (that is, demonstration of device equivalence), there is no formal stamp of approval or attestation that the measurements are accurate,” Dr. Juraschek said in an interview.

In his view, “more work is needed to understand the validity of these devices. For now, validated, cuff-based home devices are recommended for BP measurement at home, while further work is done to determine the accuracy of these cuffless technologies.”

The study was funded by Aktiia. Dr. Shah is an employee of the company. Dr. Krumholz has no relevant disclosures. Dr. Juraschek is a member of the Validate BP review committee and the AAMI sphygmomanometer committee.

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

Wearing a cuffless device on the wrist to continuously monitor blood pressure was associated with a significantly lower systolic BP at 6 months among hypertensive adults, real-world results from Europe show.

“We don’t know what they did to reduce their blood pressure,” Jay Shah, MD, Division of Cardiology, Mayo Clinic Arizona, Phoenix, told this news organization.

“The idea is that because they were exposed to their data on a continual basis, that may have prompted them to do something that led to an improvement in their blood pressure, whether it be exercise more, go to their doctor, or change their medication,” said Dr. Shah, who is also chief medical officer for Aktiia.

Dr. Shah presented the study at the Hypertension Scientific Sessions, San Diego.
 

Empowering data

The study used the Aktiia 24/7 BP monitor; Atkiia funded the trial. The monitor passively and continually monitors BP values from photoplethysmography signals collected via optical sensors at the wrist.

After initial individualized calibration using a cuff-based reference, BP measurements are displayed on a smartphone app, allowing users to consistently monitor their own BP for long periods of time.

Aktiia received CE mark in Europe in January 2021 and is currently under review by the U.S. Food and Drug Administration.

Dr. Shah and colleagues analyzed systolic BP (SBP) trends among 838 real-world Aktiia users in Europe (age 57 ± 11 years; 14% women) who consistently used the monitor for 6 months.

Altogether, they had data on 375 (± 287) app interactions, 3,646 (± 1,417) cuffless readings per user, and 9 (± 7) cuff readings per user.

Traditional cuff SBP averages were calculated monthly and compared with the SBP average of the first month. A t-test analysis was used to detect the difference in SBP between the first and successive months.

On the basis of the mean SBP calculated over 6 months, 136 participants were hypertensive (SBP > 140 mm Hg) and the rest had SBP less than 140 mm Hg.

Hypertensive users saw a statistically significant reduction in SBP of –3.2 mm Hg (95% CI, –0.70 to –5.59; P < .02), beginning at 3 months of continual cuffless BP monitoring, which was sustained through 6 months.

Among users with SBP less than 140 mm Hg, the mean SBP remained unchanged.

“The magnitude of improvement might look modest, but even a 5 mm Hg reduction in systolic BP correlates to a 10% decrease in cardiovascular risk,” Dr. Shah told this news organization.

He noted that “one of the major hurdles is that people may not be aware they have high blood pressure because they don’t feel it. And with a regular cuff, they’ll only see that number when they actually check their blood pressure, which is extremely rare, even for people who have hypertension.”

“Having the ability to show someone their continual blood pressure picture really empowers them to do something to make changes and to be aware, [as well as] to be a more active participant in their health,” Dr. Shah said.

He said that a good analogy is diabetes management, which has transitioned from single finger-stick glucose monitoring to continuous glucose monitoring that provides a complete 24/7 picture of glucose levels.

Transforming technology

Offering perspective on the study, Harlan Krumholz, MD, SM, with Yale New Haven Hospital and Yale School of Medicine, New Haven, Conn., said that having an accurate, affordable, unobtrusive cuffless continuous BP monitor would “transform” BP management.

Courtesy Yale University

“This could unlock an era of precision BP management with empowerment of patients to view and act on their numbers,” Dr. Krumholz said in an interview.

“We need data to be confident in the devices – and then research to best leverage the streams of information – and strategies to optimize its use in practice,” Dr. Krumholz added.

“Like any new innovation, we need to mitigate risks and monitor for unintended adverse consequences, but I am bullish on the future of cuffless continuous BP monitors,” Dr. Krumholz said.

Dr. Krumholz said that he “applauds Aktiia for doing studies that assess the effect of the information they are producing on BP over time. We need to know that new approaches not only generate valid information but that they can improve health.”
 

Ready for prime time?

In June, the European Society of Hypertension issued a statement noting that cuffless BP measurement is a fast-growing and promising field with considerable potential for improving hypertension awareness, management, and control, but because the accuracy of these new devices has not yet been validated, they are not yet suitable for clinical use.

Also providing perspective, Stephen Juraschek, MD, PhD, research director, Hypertension Center of Excellence at Healthcare Associates, Beth Israel Deaconess Medical Center, Boston, said that “there is a lot of interest in cuffless BP monitors due to their ease of measurement, comfort, and ability to obtain BP measurements in multiple settings and environments, and this study showed that the monitoring improved BP over time.”

“It is believed that the increased awareness and feedback may promote healthier behaviors aimed at lowering BP. However, this result should not be conflated with the accuracy of these monitors,” Dr. Juraschek cautioned.

He also noted that there is still no formally approved validation protocol by the Association for the Advancement of Medical Instrumentation.

“While a number of cuffless devices are cleared by the FDA through its 510k mechanism (that is, demonstration of device equivalence), there is no formal stamp of approval or attestation that the measurements are accurate,” Dr. Juraschek said in an interview.

In his view, “more work is needed to understand the validity of these devices. For now, validated, cuff-based home devices are recommended for BP measurement at home, while further work is done to determine the accuracy of these cuffless technologies.”

The study was funded by Aktiia. Dr. Shah is an employee of the company. Dr. Krumholz has no relevant disclosures. Dr. Juraschek is a member of the Validate BP review committee and the AAMI sphygmomanometer committee.

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

Systolic blood pressure went down safely and consistently 2 months after renal denervation achieved by ultrasound ablation in patients with uncontrolled, mild to moderate hypertension (HTN) in a key sham-controlled test of the balloon-equipped catheter.

The BP reductions were significant almost regardless of how they were measured – at home, in the office, during the day, at night, or over 24 hours – and weren’t dependent on baseline BP levels.

The 224-patient RADIANCE II Pivotal Study follows two earlier successful sham-controlled trials that used the same renal denervation catheter in other types of patients with HTN. They were RADIANCE-HTN SOLO, which entered patients with mild to moderate HTN not taking medication,  and RADIANCE-HTN TRIO, which included patients with HTN despite fixed-dose, single-pill, triple-antihypertensive therapy.

Courtesy American College of Cardiology

The consistent results of all three trials suggest that the ultrasound renal denervation (uRDN) technique “lowers blood pressure across the spectrum of hypertension,” concluded co–principal investigator Ajay J. Kirtane, MD, SM, Columbia University Irving Medical Center, New York–Presbyterian Hospital, when presenting RADIANCE II at the Transcatheter Cardiovascular Therapeutics annual meeting, sponsored by the Cardiovascular Research Foundation.

RADIANCE II, the largest of the three studies, met its prespecified primary efficacy endpoint of change in daytime ambulatory systolic BP at 2 months by showing a significant 6.3–mm Hg greater reduction in the uRDN group, compared with the sham-control group. There were no major adverse events at 30 days in either group.

The trial was similarly successful for the secondary endpoints of change in systolic BP measured in various other settings, including over 24 hours. Reductions after uRDN averaged 5-7 mm Hg greater than in the control group.

Sparse top-line results of the RADIANCE II pivotal trial were announced in July by the study’s sponsor, ReCor Medical.

Dr. Kirtane stressed in an interview that uRDN and likely any form of HTN renal denervation therapy is not a substitute for standard management. “This is really for patients in whom you’ve made best efforts to do the traditional things – lifestyle modification, medications, all of that – and yet they’re still uncontrolled.” At that point, assuming denervation therapy is available in practice, “it would be something to potentially consider.”

As a panelist after Dr. Kirtane’s formal presentation of RADIANCE II at the conference, Naomi D. Fisher, MD, who was a RADIANCE-HTN TRIO investigator, described how the treatment’s perceived intended patient population evolved over time.

“We all began with the idea that we were going to treat patients with resistant hypertension, that was going to be the first target. We have learned that those patients are far fewer than we thought,” said Dr. Fisher, who directs the hypertension service at Brigham and Women’s Hospital, Boston.

Initial estimates were that such patients with the resistant form, “meaning they require more than three drugs to control their blood pressure,” would represent 15%-20% of patients with HTN.

“We learned from our TRIO data that if you give these patients one single combined pill, lo and behold, many of them become controlled,” she said. “There is so much nonadherence out there in the world, about 50% of our patients aren’t taking their pills. It’s a hard and true fact.”

Exclude patients who aren’t adherent and “our true resistance population becomes minuscule. So, I don’t think that’s going to be the main population” for renal denervation therapy.

More likely, she said, it would be “patients who are uncontrolled and unable to take their medications. So that is going to include nonadherence, intolerance. It’s a very large category of patients. And the priorities can be stacked in favor of those who have higher cardiovascular risk.”

RADIANCE II can show the persistence of uRDN’s BP-lowering effect only out to 2 months so far, but the effect’s durability based on the RADIANCE program’s combined experience appears to be at least 2 years, Dr. Kirtane said in an interview.

“The RADIANCE II pivotal trial is a powerful, well-designed study attesting to the efficacy of renal denervation in BP lowering,” Franz H. Messerli, MD, Swiss Cardiovascular Center, University Hospital Bern, said in an interview.

The trial “shows the well-known unpredictability of antihypertensive response. We cannot predict who responds to renal denervation and who does not, and who even has a paradoxical increase in BP,” Dr. Messerli, an international hypertension expert not associated with the trial, said in an interview.  

“As long as we cannot predict the antihypertensive response to renal denervation therapy, potential synergism/antagonism with drug therapy remains an educated guess,” he said.

“Hypertension is a disease that lasts years and decades. As impressive as RADIANCE II’s 2-month snapshot is, I look forward to similar or better BP data 12 and 24 months after renal denervation,” Dr. Messerli added.

RADIANCE II entered patients with mild to moderate uncontrolled HTN, that is, a systolic BP at least 140/90 mm Hg and less than 180/120 mm Hg, who were receiving no more than two antihypertensive medications. They could have no history of cardiovascular or cerebrovascular events or uncontrolled diabetes, and their estimated glomerular filtration rate (eGFR) had to be at least 40 mL/min per 1.73 m².

After a 4-week drug washout period, patients who were clinically stable with an ambulatory BP of at least 135/85 mm Hg and less than 170/105 mm Hg underwent CT and renal angiography. Then, the 224 patients still anatomically eligible for the procedure were randomly assigned 2:1 to uRDN or a sham-control procedure: 150 and 74 patients, respectively.

At 2 months, daytime ambulatory systolic BP on average fell 7.9 mm Hg in the uRDN group and 1.8 mm Hg in the sham-control group, for a drop that was steeper by 6.3 mm Hg (P < .0001) after uRDN.

Also in the uRDN group, there was a 6.2–mm Hg larger decrease in 24-hour ambulatory systolic BP (P < .0001), a 5.8–mm Hg greater decline in nighttime ambulatory systolic BP (P < .0004), a 7.6–mm Hg steeper drop in mean home systolic BP (P < .0001), and 5.4 mm Hg more of a decrease in office-based systolic BP (P = .0035).

No significant differences were seen in subgroup analyses by sex, age, higher versus lower baseline systolic pressures, high versus low baseline eGFR, degree of abdominal obesity, U.S. versus European site, or whether patients entered before or during the COVID pandemic

Regulators have been accepting change in systolic BP as a surrogate for clinical endpoints in trials of antihypertensive therapy, whether pharmacologic or interventional, under consideration for approval. “That’s why safety endpoints are important to investigate” in these clinical trials, especially for invasive therapies like renal denervation, Dr. Kirtane observed.

That said, “in the longer-term follow-ups of the renal denervation therapies that are out there, including this one, there does not appear to be an appreciable decline in glomerular filtration rate, or any adverse safety signals that we see to date,” Dr. Kirtane said in an interview. “But we know that these are low-frequency events, so we have to be very vigilant, and we can’t get complacent about it.”

In RADIANCE II, there were zero adverse events within 30 days in both groups; the endpoint included death, new myocardial infarction, renal artery complications requiring invasive intervention, and hospitalization for major cardiovascular or hemodynamic-related events. Nor were there instances of new-onset renal artery stenosis greater than 70% documented by imaging at 6 months.

The ReCor uRDN catheter uses ultrasound energy to disrupt renal nerve signaling, a technology thought to deliver safer “burns,” compared with other renal denervation catheter technologies. It features an axially stabilizing balloon that transmits ultrasound energy – two to three sonications, each lasting 7 seconds, Dr. Kirtane said – outward through the arterial wall. The design is intended to ensure consistently circumferential ablation. Circulating saline within the balloon, Kirtane noted, directly cools the adjacent vessel wall to help it avoid thermal damage.

Dr. Kirtane reported receiving institutional funding from Medtronic, Boston Scientific, Abbott Vascular, Amgen, CSI, Philips, ReCor Medical, Neurotronic, Biotronik, Chiesi, Bolt Medical, Magenta Medical, Canon, SoniVie, Shockwave Medical, and Merck; consulting for IMDS; and receiving travel and meal expenses from Medtronic, Boston Scientific, Abbott Vascular, CSI, Siemens, Philips, ReCor Medical, Chiesi, OpSens, Zoll, and Regeneron. Dr. Fisher disclosed receiving honoraria or fees for consulting or serving on a speaker’s bureau for Medtronic, ReCor Medical, and Aktiia and receiving grant support or holding research contracts for Recor Medical and Aktiia. Dr. Messerli disclosed receiving honoraria from Medtronic, Menarini, Krka, and Ipca.

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

Systolic blood pressure went down safely and consistently 2 months after renal denervation achieved by ultrasound ablation in patients with uncontrolled, mild to moderate hypertension (HTN) in a key sham-controlled test of the balloon-equipped catheter.

The BP reductions were significant almost regardless of how they were measured – at home, in the office, during the day, at night, or over 24 hours – and weren’t dependent on baseline BP levels.

The 224-patient RADIANCE II Pivotal Study follows two earlier successful sham-controlled trials that used the same renal denervation catheter in other types of patients with HTN. They were RADIANCE-HTN SOLO, which entered patients with mild to moderate HTN not taking medication,  and RADIANCE-HTN TRIO, which included patients with HTN despite fixed-dose, single-pill, triple-antihypertensive therapy.

Courtesy American College of Cardiology

The consistent results of all three trials suggest that the ultrasound renal denervation (uRDN) technique “lowers blood pressure across the spectrum of hypertension,” concluded co–principal investigator Ajay J. Kirtane, MD, SM, Columbia University Irving Medical Center, New York–Presbyterian Hospital, when presenting RADIANCE II at the Transcatheter Cardiovascular Therapeutics annual meeting, sponsored by the Cardiovascular Research Foundation.

RADIANCE II, the largest of the three studies, met its prespecified primary efficacy endpoint of change in daytime ambulatory systolic BP at 2 months by showing a significant 6.3–mm Hg greater reduction in the uRDN group, compared with the sham-control group. There were no major adverse events at 30 days in either group.

The trial was similarly successful for the secondary endpoints of change in systolic BP measured in various other settings, including over 24 hours. Reductions after uRDN averaged 5-7 mm Hg greater than in the control group.

Sparse top-line results of the RADIANCE II pivotal trial were announced in July by the study’s sponsor, ReCor Medical.

Dr. Kirtane stressed in an interview that uRDN and likely any form of HTN renal denervation therapy is not a substitute for standard management. “This is really for patients in whom you’ve made best efforts to do the traditional things – lifestyle modification, medications, all of that – and yet they’re still uncontrolled.” At that point, assuming denervation therapy is available in practice, “it would be something to potentially consider.”

As a panelist after Dr. Kirtane’s formal presentation of RADIANCE II at the conference, Naomi D. Fisher, MD, who was a RADIANCE-HTN TRIO investigator, described how the treatment’s perceived intended patient population evolved over time.

“We all began with the idea that we were going to treat patients with resistant hypertension, that was going to be the first target. We have learned that those patients are far fewer than we thought,” said Dr. Fisher, who directs the hypertension service at Brigham and Women’s Hospital, Boston.

Initial estimates were that such patients with the resistant form, “meaning they require more than three drugs to control their blood pressure,” would represent 15%-20% of patients with HTN.

“We learned from our TRIO data that if you give these patients one single combined pill, lo and behold, many of them become controlled,” she said. “There is so much nonadherence out there in the world, about 50% of our patients aren’t taking their pills. It’s a hard and true fact.”

Exclude patients who aren’t adherent and “our true resistance population becomes minuscule. So, I don’t think that’s going to be the main population” for renal denervation therapy.

More likely, she said, it would be “patients who are uncontrolled and unable to take their medications. So that is going to include nonadherence, intolerance. It’s a very large category of patients. And the priorities can be stacked in favor of those who have higher cardiovascular risk.”

RADIANCE II can show the persistence of uRDN’s BP-lowering effect only out to 2 months so far, but the effect’s durability based on the RADIANCE program’s combined experience appears to be at least 2 years, Dr. Kirtane said in an interview.

“The RADIANCE II pivotal trial is a powerful, well-designed study attesting to the efficacy of renal denervation in BP lowering,” Franz H. Messerli, MD, Swiss Cardiovascular Center, University Hospital Bern, said in an interview.

The trial “shows the well-known unpredictability of antihypertensive response. We cannot predict who responds to renal denervation and who does not, and who even has a paradoxical increase in BP,” Dr. Messerli, an international hypertension expert not associated with the trial, said in an interview.  

“As long as we cannot predict the antihypertensive response to renal denervation therapy, potential synergism/antagonism with drug therapy remains an educated guess,” he said.

“Hypertension is a disease that lasts years and decades. As impressive as RADIANCE II’s 2-month snapshot is, I look forward to similar or better BP data 12 and 24 months after renal denervation,” Dr. Messerli added.

RADIANCE II entered patients with mild to moderate uncontrolled HTN, that is, a systolic BP at least 140/90 mm Hg and less than 180/120 mm Hg, who were receiving no more than two antihypertensive medications. They could have no history of cardiovascular or cerebrovascular events or uncontrolled diabetes, and their estimated glomerular filtration rate (eGFR) had to be at least 40 mL/min per 1.73 m².

After a 4-week drug washout period, patients who were clinically stable with an ambulatory BP of at least 135/85 mm Hg and less than 170/105 mm Hg underwent CT and renal angiography. Then, the 224 patients still anatomically eligible for the procedure were randomly assigned 2:1 to uRDN or a sham-control procedure: 150 and 74 patients, respectively.

At 2 months, daytime ambulatory systolic BP on average fell 7.9 mm Hg in the uRDN group and 1.8 mm Hg in the sham-control group, for a drop that was steeper by 6.3 mm Hg (P < .0001) after uRDN.

Also in the uRDN group, there was a 6.2–mm Hg larger decrease in 24-hour ambulatory systolic BP (P < .0001), a 5.8–mm Hg greater decline in nighttime ambulatory systolic BP (P < .0004), a 7.6–mm Hg steeper drop in mean home systolic BP (P < .0001), and 5.4 mm Hg more of a decrease in office-based systolic BP (P = .0035).

No significant differences were seen in subgroup analyses by sex, age, higher versus lower baseline systolic pressures, high versus low baseline eGFR, degree of abdominal obesity, U.S. versus European site, or whether patients entered before or during the COVID pandemic

Regulators have been accepting change in systolic BP as a surrogate for clinical endpoints in trials of antihypertensive therapy, whether pharmacologic or interventional, under consideration for approval. “That’s why safety endpoints are important to investigate” in these clinical trials, especially for invasive therapies like renal denervation, Dr. Kirtane observed.

That said, “in the longer-term follow-ups of the renal denervation therapies that are out there, including this one, there does not appear to be an appreciable decline in glomerular filtration rate, or any adverse safety signals that we see to date,” Dr. Kirtane said in an interview. “But we know that these are low-frequency events, so we have to be very vigilant, and we can’t get complacent about it.”

In RADIANCE II, there were zero adverse events within 30 days in both groups; the endpoint included death, new myocardial infarction, renal artery complications requiring invasive intervention, and hospitalization for major cardiovascular or hemodynamic-related events. Nor were there instances of new-onset renal artery stenosis greater than 70% documented by imaging at 6 months.

The ReCor uRDN catheter uses ultrasound energy to disrupt renal nerve signaling, a technology thought to deliver safer “burns,” compared with other renal denervation catheter technologies. It features an axially stabilizing balloon that transmits ultrasound energy – two to three sonications, each lasting 7 seconds, Dr. Kirtane said – outward through the arterial wall. The design is intended to ensure consistently circumferential ablation. Circulating saline within the balloon, Kirtane noted, directly cools the adjacent vessel wall to help it avoid thermal damage.

Dr. Kirtane reported receiving institutional funding from Medtronic, Boston Scientific, Abbott Vascular, Amgen, CSI, Philips, ReCor Medical, Neurotronic, Biotronik, Chiesi, Bolt Medical, Magenta Medical, Canon, SoniVie, Shockwave Medical, and Merck; consulting for IMDS; and receiving travel and meal expenses from Medtronic, Boston Scientific, Abbott Vascular, CSI, Siemens, Philips, ReCor Medical, Chiesi, OpSens, Zoll, and Regeneron. Dr. Fisher disclosed receiving honoraria or fees for consulting or serving on a speaker’s bureau for Medtronic, ReCor Medical, and Aktiia and receiving grant support or holding research contracts for Recor Medical and Aktiia. Dr. Messerli disclosed receiving honoraria from Medtronic, Menarini, Krka, and Ipca.

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

Systolic blood pressure went down safely and consistently 2 months after renal denervation achieved by ultrasound ablation in patients with uncontrolled, mild to moderate hypertension (HTN) in a key sham-controlled test of the balloon-equipped catheter.

The BP reductions were significant almost regardless of how they were measured – at home, in the office, during the day, at night, or over 24 hours – and weren’t dependent on baseline BP levels.

The 224-patient RADIANCE II Pivotal Study follows two earlier successful sham-controlled trials that used the same renal denervation catheter in other types of patients with HTN. They were RADIANCE-HTN SOLO, which entered patients with mild to moderate HTN not taking medication,  and RADIANCE-HTN TRIO, which included patients with HTN despite fixed-dose, single-pill, triple-antihypertensive therapy.

Courtesy American College of Cardiology

The consistent results of all three trials suggest that the ultrasound renal denervation (uRDN) technique “lowers blood pressure across the spectrum of hypertension,” concluded co–principal investigator Ajay J. Kirtane, MD, SM, Columbia University Irving Medical Center, New York–Presbyterian Hospital, when presenting RADIANCE II at the Transcatheter Cardiovascular Therapeutics annual meeting, sponsored by the Cardiovascular Research Foundation.

RADIANCE II, the largest of the three studies, met its prespecified primary efficacy endpoint of change in daytime ambulatory systolic BP at 2 months by showing a significant 6.3–mm Hg greater reduction in the uRDN group, compared with the sham-control group. There were no major adverse events at 30 days in either group.

The trial was similarly successful for the secondary endpoints of change in systolic BP measured in various other settings, including over 24 hours. Reductions after uRDN averaged 5-7 mm Hg greater than in the control group.

Sparse top-line results of the RADIANCE II pivotal trial were announced in July by the study’s sponsor, ReCor Medical.

Dr. Kirtane stressed in an interview that uRDN and likely any form of HTN renal denervation therapy is not a substitute for standard management. “This is really for patients in whom you’ve made best efforts to do the traditional things – lifestyle modification, medications, all of that – and yet they’re still uncontrolled.” At that point, assuming denervation therapy is available in practice, “it would be something to potentially consider.”

As a panelist after Dr. Kirtane’s formal presentation of RADIANCE II at the conference, Naomi D. Fisher, MD, who was a RADIANCE-HTN TRIO investigator, described how the treatment’s perceived intended patient population evolved over time.

“We all began with the idea that we were going to treat patients with resistant hypertension, that was going to be the first target. We have learned that those patients are far fewer than we thought,” said Dr. Fisher, who directs the hypertension service at Brigham and Women’s Hospital, Boston.

Initial estimates were that such patients with the resistant form, “meaning they require more than three drugs to control their blood pressure,” would represent 15%-20% of patients with HTN.

“We learned from our TRIO data that if you give these patients one single combined pill, lo and behold, many of them become controlled,” she said. “There is so much nonadherence out there in the world, about 50% of our patients aren’t taking their pills. It’s a hard and true fact.”

Exclude patients who aren’t adherent and “our true resistance population becomes minuscule. So, I don’t think that’s going to be the main population” for renal denervation therapy.

More likely, she said, it would be “patients who are uncontrolled and unable to take their medications. So that is going to include nonadherence, intolerance. It’s a very large category of patients. And the priorities can be stacked in favor of those who have higher cardiovascular risk.”

RADIANCE II can show the persistence of uRDN’s BP-lowering effect only out to 2 months so far, but the effect’s durability based on the RADIANCE program’s combined experience appears to be at least 2 years, Dr. Kirtane said in an interview.

“The RADIANCE II pivotal trial is a powerful, well-designed study attesting to the efficacy of renal denervation in BP lowering,” Franz H. Messerli, MD, Swiss Cardiovascular Center, University Hospital Bern, said in an interview.

The trial “shows the well-known unpredictability of antihypertensive response. We cannot predict who responds to renal denervation and who does not, and who even has a paradoxical increase in BP,” Dr. Messerli, an international hypertension expert not associated with the trial, said in an interview.  

“As long as we cannot predict the antihypertensive response to renal denervation therapy, potential synergism/antagonism with drug therapy remains an educated guess,” he said.

“Hypertension is a disease that lasts years and decades. As impressive as RADIANCE II’s 2-month snapshot is, I look forward to similar or better BP data 12 and 24 months after renal denervation,” Dr. Messerli added.

RADIANCE II entered patients with mild to moderate uncontrolled HTN, that is, a systolic BP at least 140/90 mm Hg and less than 180/120 mm Hg, who were receiving no more than two antihypertensive medications. They could have no history of cardiovascular or cerebrovascular events or uncontrolled diabetes, and their estimated glomerular filtration rate (eGFR) had to be at least 40 mL/min per 1.73 m².

After a 4-week drug washout period, patients who were clinically stable with an ambulatory BP of at least 135/85 mm Hg and less than 170/105 mm Hg underwent CT and renal angiography. Then, the 224 patients still anatomically eligible for the procedure were randomly assigned 2:1 to uRDN or a sham-control procedure: 150 and 74 patients, respectively.

At 2 months, daytime ambulatory systolic BP on average fell 7.9 mm Hg in the uRDN group and 1.8 mm Hg in the sham-control group, for a drop that was steeper by 6.3 mm Hg (P < .0001) after uRDN.

Also in the uRDN group, there was a 6.2–mm Hg larger decrease in 24-hour ambulatory systolic BP (P < .0001), a 5.8–mm Hg greater decline in nighttime ambulatory systolic BP (P < .0004), a 7.6–mm Hg steeper drop in mean home systolic BP (P < .0001), and 5.4 mm Hg more of a decrease in office-based systolic BP (P = .0035).

No significant differences were seen in subgroup analyses by sex, age, higher versus lower baseline systolic pressures, high versus low baseline eGFR, degree of abdominal obesity, U.S. versus European site, or whether patients entered before or during the COVID pandemic

Regulators have been accepting change in systolic BP as a surrogate for clinical endpoints in trials of antihypertensive therapy, whether pharmacologic or interventional, under consideration for approval. “That’s why safety endpoints are important to investigate” in these clinical trials, especially for invasive therapies like renal denervation, Dr. Kirtane observed.

That said, “in the longer-term follow-ups of the renal denervation therapies that are out there, including this one, there does not appear to be an appreciable decline in glomerular filtration rate, or any adverse safety signals that we see to date,” Dr. Kirtane said in an interview. “But we know that these are low-frequency events, so we have to be very vigilant, and we can’t get complacent about it.”

In RADIANCE II, there were zero adverse events within 30 days in both groups; the endpoint included death, new myocardial infarction, renal artery complications requiring invasive intervention, and hospitalization for major cardiovascular or hemodynamic-related events. Nor were there instances of new-onset renal artery stenosis greater than 70% documented by imaging at 6 months.

The ReCor uRDN catheter uses ultrasound energy to disrupt renal nerve signaling, a technology thought to deliver safer “burns,” compared with other renal denervation catheter technologies. It features an axially stabilizing balloon that transmits ultrasound energy – two to three sonications, each lasting 7 seconds, Dr. Kirtane said – outward through the arterial wall. The design is intended to ensure consistently circumferential ablation. Circulating saline within the balloon, Kirtane noted, directly cools the adjacent vessel wall to help it avoid thermal damage.

Dr. Kirtane reported receiving institutional funding from Medtronic, Boston Scientific, Abbott Vascular, Amgen, CSI, Philips, ReCor Medical, Neurotronic, Biotronik, Chiesi, Bolt Medical, Magenta Medical, Canon, SoniVie, Shockwave Medical, and Merck; consulting for IMDS; and receiving travel and meal expenses from Medtronic, Boston Scientific, Abbott Vascular, CSI, Siemens, Philips, ReCor Medical, Chiesi, OpSens, Zoll, and Regeneron. Dr. Fisher disclosed receiving honoraria or fees for consulting or serving on a speaker’s bureau for Medtronic, ReCor Medical, and Aktiia and receiving grant support or holding research contracts for Recor Medical and Aktiia. Dr. Messerli disclosed receiving honoraria from Medtronic, Menarini, Krka, and Ipca.

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

Among patients with severe isolated aortic stenosis younger than 65, the rate of transcatheter aortic valve replacement (TAVR) now almost matches that of surgical aortic valve replacement (SAVR), despite guideline recommendations to the contrary, a study in a national U.S. population shows.

The 2020 American Heart Association/American College of Cardiology (AHA/ACC) valve guideline recommends SAVR for patients younger than 65 with severe aortic stenosis, the researchers note, but their study showed “near equal utilization between TAVR and SAVR in these younger patients by 2021,” at 48% and 52% respectively.

Toishi Sharma, MD, and colleagues presented these findings in an oral poster session at Transcatheter Cardiovascular Therapeutics 2022, and the study was simultaneously published as a Research Letter in the Journal of the American College of Cardiology (JACC).

“To our knowledge, the current findings represent the first national temporal trends study stratifying [aortic stenosis] therapies according to guideline-recommended age groups: our observations demonstrate the dramatic growth of TAVR in all age groups, including young patients,” the researchers conclude.

They analyzed changes in rates of TAVR and SAVR in a U.S. sample stratified by age: younger than 65 years, 65-80, and older than 80 years.

These findings have implications for lifetime management of younger patients who undergo TAVR, they write, “including issues related to lifetime coronary access, valve durability, and the potential for subsequent TAVR procedures over time.”
 

Three age groups

In a study published in JACC, this group examined changes in uptake of TAVR versus SAVR in 4,161 patients with aortic stenosis in Vermont, New Hampshire, and Maine, senior author Harold L. Dauerman, MD, said in an interview.

The greatest rate of rise of TAVR was in the group younger than 65, but that study ended in 2019, said Dr. Dauerman, from the University of Vermont Health Network, Burlington.

The 2020 guideline stratifies TAVR and SAVR recommendations such that “less than 65 should primarily be a surgical approach and greater than 80 primarily a TAVR approach, while 65 to 80 is a gray zone, and shared decision-making becomes important,” he noted.

The group hypothesized that recent trials and technology have led to a national increase in TAVR in people younger than 65.

From the Vizient clinical database, including more than 250 U.S. academic centers that perform both TAVR and SAVR, the researchers identified 142,953 patients who underwent TAVR or SAVR for isolated aortic stenosis from Oct. 1, 2015, to Dec. 31, 2021. From 2015 to 2021, the valve replacement rates in the three age groups changed as follows:

• Age less than 65: TAVR rose from 17% to 48%; SAVR fell from 83% to 52%.
• Age 65-80: TAVR rose from 46% to 87%; SAVR fell from 54% to 12%.
• Age greater than 80: TAVR rose from 83% to 99%; SAVR fell from 16% to 1%.

“All ages have grown in the last 7 years in TAVR,” Dr. Dauerman summarized. “The one that’s surprising, and in contradiction to the guideline, is the growth of TAVR in young patients less than 65.”

Among patients younger than 65, prior bypass surgery and congestive heart failure predicted the use of TAVR instead of surgery, whereas bicuspid aortic valve disease was the biggest predictor of surgery instead of TAVR.

Most studies on TAVR valve durability are limited to patients in the randomized trials who were primarily in their mid-70s to mid-80s, some of whom died before a 10-year follow-up, Dr. Dauerman noted.

European guidelines recommend surgery for patients younger than 70, and it would be interesting to see if clinicians there follow this recommendation or if TAVR is now the preferred approach, he added.

There is a need for further, longer study of TAVR in younger patients, he said, to determine whether there are long-term clinical issues of concern.
 

Strategy depends on more than age

The “findings are not too surprising,” John Carroll, MD, who was not involved in this research, said in an email.

University of Colorado Hospital

“Age is only one of multiple patient characteristics that enter into consideration of TAVR versus SAVR,” said Dr. Carroll, from Anschutz Medical Campus, University of Colorado, Aurora.

“As the article reports,” he noted, “those less than 65 having TAVR are more likely to have comorbid conditions that likely made the risk of SAVR higher.”

Dr. Carroll was lead author of a review article published in 2020 based on data from the ACC–Society of Thoracic Surgeons (STS)–Transcatheter Valve Therapy (TVT) registry on 276,316 patients who had TAVR in the United States from 2011-2019.

He pointed out that Figure 2 in that review shows that “SAVR is often performed in conjunction with other surgical procedures – another major reason why SAVR remains an important treatment for valvular heart disease.”

“We are awaiting long-term data comparing TAVR to SAVR durability,” Dr. Carroll added, echoing Dr. Dauerman. “So far [there are] no major differences, but it remains a key need to fully understand TAVR and the various models in commercial use.”

“Both TAVR and SAVR used in adults are tissue valves (SAVR with mechanical valves is used in younger patients),” Dr. Carroll noted, “and all tissue valves will eventually fail if the patient lives long enough.”

Patient management strategies need to consider what treatment options exist when the first valve fails. “If the first valve is SAVR, there is now extensive experience with placing a TAVR valve inside a failing SAVR valve, so called Valve-in-Valve or TAVR-in-SAVR. This is the preferred treatment in most patients with failing SAVR valves,” he said.

“On the other hand,” he continued, “we are just beginning to see more and more patients with failing TAVR valves, and the TAVR-in-TAVR procedure is less well understood.”

“Issues such as acute coronary occlusion and long-term difficulty in accessing coronary arteries are being encountered in some patients having TAVR-in-TAVR,” Dr. Carroll noted, which he discusses in a recent editorial he coauthored about the complexities of redo TAVR, published in JACC: Cardiovascular Interventions.

The study received no funding. Dr. Dauerman has research grants and is a consultant for Medtronic and Boston Scientific. Dr. Carroll is a local principal investigator in trials sponsored by Medtronic, Abbott, and Edwards Lifesciences.

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

Among patients with severe isolated aortic stenosis younger than 65, the rate of transcatheter aortic valve replacement (TAVR) now almost matches that of surgical aortic valve replacement (SAVR), despite guideline recommendations to the contrary, a study in a national U.S. population shows.

The 2020 American Heart Association/American College of Cardiology (AHA/ACC) valve guideline recommends SAVR for patients younger than 65 with severe aortic stenosis, the researchers note, but their study showed “near equal utilization between TAVR and SAVR in these younger patients by 2021,” at 48% and 52% respectively.

Toishi Sharma, MD, and colleagues presented these findings in an oral poster session at Transcatheter Cardiovascular Therapeutics 2022, and the study was simultaneously published as a Research Letter in the Journal of the American College of Cardiology (JACC).

“To our knowledge, the current findings represent the first national temporal trends study stratifying [aortic stenosis] therapies according to guideline-recommended age groups: our observations demonstrate the dramatic growth of TAVR in all age groups, including young patients,” the researchers conclude.

They analyzed changes in rates of TAVR and SAVR in a U.S. sample stratified by age: younger than 65 years, 65-80, and older than 80 years.

These findings have implications for lifetime management of younger patients who undergo TAVR, they write, “including issues related to lifetime coronary access, valve durability, and the potential for subsequent TAVR procedures over time.”
 

Three age groups

In a study published in JACC, this group examined changes in uptake of TAVR versus SAVR in 4,161 patients with aortic stenosis in Vermont, New Hampshire, and Maine, senior author Harold L. Dauerman, MD, said in an interview.

The greatest rate of rise of TAVR was in the group younger than 65, but that study ended in 2019, said Dr. Dauerman, from the University of Vermont Health Network, Burlington.

The 2020 guideline stratifies TAVR and SAVR recommendations such that “less than 65 should primarily be a surgical approach and greater than 80 primarily a TAVR approach, while 65 to 80 is a gray zone, and shared decision-making becomes important,” he noted.

The group hypothesized that recent trials and technology have led to a national increase in TAVR in people younger than 65.

From the Vizient clinical database, including more than 250 U.S. academic centers that perform both TAVR and SAVR, the researchers identified 142,953 patients who underwent TAVR or SAVR for isolated aortic stenosis from Oct. 1, 2015, to Dec. 31, 2021. From 2015 to 2021, the valve replacement rates in the three age groups changed as follows:

• Age less than 65: TAVR rose from 17% to 48%; SAVR fell from 83% to 52%.
• Age 65-80: TAVR rose from 46% to 87%; SAVR fell from 54% to 12%.
• Age greater than 80: TAVR rose from 83% to 99%; SAVR fell from 16% to 1%.

“All ages have grown in the last 7 years in TAVR,” Dr. Dauerman summarized. “The one that’s surprising, and in contradiction to the guideline, is the growth of TAVR in young patients less than 65.”

Among patients younger than 65, prior bypass surgery and congestive heart failure predicted the use of TAVR instead of surgery, whereas bicuspid aortic valve disease was the biggest predictor of surgery instead of TAVR.

Most studies on TAVR valve durability are limited to patients in the randomized trials who were primarily in their mid-70s to mid-80s, some of whom died before a 10-year follow-up, Dr. Dauerman noted.

European guidelines recommend surgery for patients younger than 70, and it would be interesting to see if clinicians there follow this recommendation or if TAVR is now the preferred approach, he added.

There is a need for further, longer study of TAVR in younger patients, he said, to determine whether there are long-term clinical issues of concern.
 

Strategy depends on more than age

The “findings are not too surprising,” John Carroll, MD, who was not involved in this research, said in an email.

University of Colorado Hospital

“Age is only one of multiple patient characteristics that enter into consideration of TAVR versus SAVR,” said Dr. Carroll, from Anschutz Medical Campus, University of Colorado, Aurora.

“As the article reports,” he noted, “those less than 65 having TAVR are more likely to have comorbid conditions that likely made the risk of SAVR higher.”

Dr. Carroll was lead author of a review article published in 2020 based on data from the ACC–Society of Thoracic Surgeons (STS)–Transcatheter Valve Therapy (TVT) registry on 276,316 patients who had TAVR in the United States from 2011-2019.

He pointed out that Figure 2 in that review shows that “SAVR is often performed in conjunction with other surgical procedures – another major reason why SAVR remains an important treatment for valvular heart disease.”

“We are awaiting long-term data comparing TAVR to SAVR durability,” Dr. Carroll added, echoing Dr. Dauerman. “So far [there are] no major differences, but it remains a key need to fully understand TAVR and the various models in commercial use.”

“Both TAVR and SAVR used in adults are tissue valves (SAVR with mechanical valves is used in younger patients),” Dr. Carroll noted, “and all tissue valves will eventually fail if the patient lives long enough.”

Patient management strategies need to consider what treatment options exist when the first valve fails. “If the first valve is SAVR, there is now extensive experience with placing a TAVR valve inside a failing SAVR valve, so called Valve-in-Valve or TAVR-in-SAVR. This is the preferred treatment in most patients with failing SAVR valves,” he said.

“On the other hand,” he continued, “we are just beginning to see more and more patients with failing TAVR valves, and the TAVR-in-TAVR procedure is less well understood.”

“Issues such as acute coronary occlusion and long-term difficulty in accessing coronary arteries are being encountered in some patients having TAVR-in-TAVR,” Dr. Carroll noted, which he discusses in a recent editorial he coauthored about the complexities of redo TAVR, published in JACC: Cardiovascular Interventions.

The study received no funding. Dr. Dauerman has research grants and is a consultant for Medtronic and Boston Scientific. Dr. Carroll is a local principal investigator in trials sponsored by Medtronic, Abbott, and Edwards Lifesciences.

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

Among patients with severe isolated aortic stenosis younger than 65, the rate of transcatheter aortic valve replacement (TAVR) now almost matches that of surgical aortic valve replacement (SAVR), despite guideline recommendations to the contrary, a study in a national U.S. population shows.

The 2020 American Heart Association/American College of Cardiology (AHA/ACC) valve guideline recommends SAVR for patients younger than 65 with severe aortic stenosis, the researchers note, but their study showed “near equal utilization between TAVR and SAVR in these younger patients by 2021,” at 48% and 52% respectively.

Toishi Sharma, MD, and colleagues presented these findings in an oral poster session at Transcatheter Cardiovascular Therapeutics 2022, and the study was simultaneously published as a Research Letter in the Journal of the American College of Cardiology (JACC).

“To our knowledge, the current findings represent the first national temporal trends study stratifying [aortic stenosis] therapies according to guideline-recommended age groups: our observations demonstrate the dramatic growth of TAVR in all age groups, including young patients,” the researchers conclude.

They analyzed changes in rates of TAVR and SAVR in a U.S. sample stratified by age: younger than 65 years, 65-80, and older than 80 years.

These findings have implications for lifetime management of younger patients who undergo TAVR, they write, “including issues related to lifetime coronary access, valve durability, and the potential for subsequent TAVR procedures over time.”
 

Three age groups

In a study published in JACC, this group examined changes in uptake of TAVR versus SAVR in 4,161 patients with aortic stenosis in Vermont, New Hampshire, and Maine, senior author Harold L. Dauerman, MD, said in an interview.

The greatest rate of rise of TAVR was in the group younger than 65, but that study ended in 2019, said Dr. Dauerman, from the University of Vermont Health Network, Burlington.

The 2020 guideline stratifies TAVR and SAVR recommendations such that “less than 65 should primarily be a surgical approach and greater than 80 primarily a TAVR approach, while 65 to 80 is a gray zone, and shared decision-making becomes important,” he noted.

The group hypothesized that recent trials and technology have led to a national increase in TAVR in people younger than 65.

From the Vizient clinical database, including more than 250 U.S. academic centers that perform both TAVR and SAVR, the researchers identified 142,953 patients who underwent TAVR or SAVR for isolated aortic stenosis from Oct. 1, 2015, to Dec. 31, 2021. From 2015 to 2021, the valve replacement rates in the three age groups changed as follows:

• Age less than 65: TAVR rose from 17% to 48%; SAVR fell from 83% to 52%.
• Age 65-80: TAVR rose from 46% to 87%; SAVR fell from 54% to 12%.
• Age greater than 80: TAVR rose from 83% to 99%; SAVR fell from 16% to 1%.

“All ages have grown in the last 7 years in TAVR,” Dr. Dauerman summarized. “The one that’s surprising, and in contradiction to the guideline, is the growth of TAVR in young patients less than 65.”

Among patients younger than 65, prior bypass surgery and congestive heart failure predicted the use of TAVR instead of surgery, whereas bicuspid aortic valve disease was the biggest predictor of surgery instead of TAVR.

Most studies on TAVR valve durability are limited to patients in the randomized trials who were primarily in their mid-70s to mid-80s, some of whom died before a 10-year follow-up, Dr. Dauerman noted.

European guidelines recommend surgery for patients younger than 70, and it would be interesting to see if clinicians there follow this recommendation or if TAVR is now the preferred approach, he added.

There is a need for further, longer study of TAVR in younger patients, he said, to determine whether there are long-term clinical issues of concern.
 

Strategy depends on more than age

The “findings are not too surprising,” John Carroll, MD, who was not involved in this research, said in an email.

University of Colorado Hospital

“Age is only one of multiple patient characteristics that enter into consideration of TAVR versus SAVR,” said Dr. Carroll, from Anschutz Medical Campus, University of Colorado, Aurora.

“As the article reports,” he noted, “those less than 65 having TAVR are more likely to have comorbid conditions that likely made the risk of SAVR higher.”

Dr. Carroll was lead author of a review article published in 2020 based on data from the ACC–Society of Thoracic Surgeons (STS)–Transcatheter Valve Therapy (TVT) registry on 276,316 patients who had TAVR in the United States from 2011-2019.

He pointed out that Figure 2 in that review shows that “SAVR is often performed in conjunction with other surgical procedures – another major reason why SAVR remains an important treatment for valvular heart disease.”

“We are awaiting long-term data comparing TAVR to SAVR durability,” Dr. Carroll added, echoing Dr. Dauerman. “So far [there are] no major differences, but it remains a key need to fully understand TAVR and the various models in commercial use.”

“Both TAVR and SAVR used in adults are tissue valves (SAVR with mechanical valves is used in younger patients),” Dr. Carroll noted, “and all tissue valves will eventually fail if the patient lives long enough.”

Patient management strategies need to consider what treatment options exist when the first valve fails. “If the first valve is SAVR, there is now extensive experience with placing a TAVR valve inside a failing SAVR valve, so called Valve-in-Valve or TAVR-in-SAVR. This is the preferred treatment in most patients with failing SAVR valves,” he said.

“On the other hand,” he continued, “we are just beginning to see more and more patients with failing TAVR valves, and the TAVR-in-TAVR procedure is less well understood.”

“Issues such as acute coronary occlusion and long-term difficulty in accessing coronary arteries are being encountered in some patients having TAVR-in-TAVR,” Dr. Carroll noted, which he discusses in a recent editorial he coauthored about the complexities of redo TAVR, published in JACC: Cardiovascular Interventions.

The study received no funding. Dr. Dauerman has research grants and is a consultant for Medtronic and Boston Scientific. Dr. Carroll is a local principal investigator in trials sponsored by Medtronic, Abbott, and Edwards Lifesciences.

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

In patients with severe mitral regurgitation (MR) and cardiogenic shock, successful transcatheter edge-to-edge repair (TEER) is associated with a substantial reduction in all-cause mortality and lower morbidity at 1 year, according to an analysis of registry data.

The data from this analysis also confirm that “successful reduction of MR is achievable with TEER in most patients with cardiogenic shock,” reported Mohamad A. Alkhouli, MD, an interventional cardiologist and professor of medicine at the Mayo Clinic, Rochester, Minn.

STS/ACC TCT registry data queried

Drawn from the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry, 3,797 patients with cardiogenic shock underwent MR repair between November 2013 and December 2021. Outcomes at 1 year were evaluable in 2,773 of these patients. For inclusion, all had to meet at least one of the definitions of cardiogenic shock, such as inotrope use or mechanical circulatory support.

At baseline, 94.5% had a MR severity of at least 3+, and most of these had 4+. Thirty days after treatment, 88.8% had MR severity of 2+ or less, the majority of which had a severity of 1+.

These data address an important question not previously well studied, according to Dr. Alkhouli. In MR patients, cardiogenic shock is associated with a high risk of death, but there has been little evidence that valve repair does not exacerbate, let alone modify, this risk.

These data support the value of intervention, which was performed in almost all patients with MitraClipä (Abbott), the only device available for most of the period in which the registry was queried. However, Dr. Alkhouli cautioned that his data are best considered “hypothesis generating.”

“We need a randomized trial,” he said at the meeting sponsored by the Cardiovascular Research Foundation. He pointed out that this is a complex population for which multiple variables might have skewed results when data are analyzed retrospectively. Not least, those MR patients with cardiogenic shock in the database considered for TEER might well have been relatively healthy and not representative of an unselected population with both MR and cardiogenic shock.

The question might be better answered by the multicenter Canadian trial CAPITAL MINOS, which has just started. Described in an article in the American Heart Journal, it has a planned enrollment of about 150 MR patients with cardiogenic shock randomized to TEER or medical therapy. Results are expected in about 1 year, according to Dr. Alkhouli.

But regarding the present analysis, Dr. Alkhouli did note that sensitivity analyses conducted within his data across risk factors, such as degenerative versus nondegenerative MR, low (< 30%) versus higher left ventricular ejection fraction (LVEF), and presence or absence of an acute coronary syndrome (ACS), consistently supported a benefit from intervention.

Also, cardiogenic shock did not appear to be a factor in device failure, according to Dr. Alkhouli, addressing a potential criticism that cardiogenic shock was an underlying reason for device failure.
 

More than 90% in NYHA class III or IV heart failure

In this study, the mean age was 73 years. More than 90% were in class III or IV heart failure in the 2 weeks prior to TEER. More than half had established coronary artery disease. Other concomitant cardiovascular morbidities, including atrial fibrillation or flutter (65%), prior MI (39%), and prior stroke or transient ischemic attach (> 10%) were well represented.

When those with device success were compared with those with device failure, the risk profile was comparable. The predicted STS (Society of Thoracic Surgeons) mortality for mitral valve repair among these two groups was 14.8% versus 15% (P = 0.97), respectively.

However, those with device failure did have a lower baseline left ventricular ejection fraction (40.7% vs. 42.9%; P = .009) and a greater prevalence of moderate-to-severe or severe MR (96.1% vs. 84.9%; P < 0.001).

The growing experience with TEER means that benefit has now been shown in several complicated MR groups, such as those with severe ventricular dysfunction, renal insufficiency, and obstructive lung disease. This was a rationale for looking at the impact or repairing MR in patients with cardiogenic shock.

It is a pressing question, according to Dr. Alkhouli. He cited studies suggesting that up to 20% of patients hospitalized for cardiogenic shock have at least moderate-to-severe MR. Conversely, cardiogenic shock is not an uncommon finding in patients with MR.

While Dr. Alkhouli acknowledged that the many variables influencing outcome in patients with MR and cardiogenic shock will make a randomized trial “challenging,” many experts echoed this concern and even expressed some skepticism about the potential for an unbiased trial.
 

Data confirm MR repair is safe during shock

“These data do show that repair of MR is safe in patients safe in patients with cardiogenic shock,” said Anita W. Asgar, MD, an interventional cardiologist associated with the Montreal Heart Institute. She noted that there was a 5- to 6-day delay among the cardiogenic shock patients prior to undergoing MR repair in this analysis, potentially reflecting an elimination of those at very high risk. Similarly, she suggested that many interventionalists are likely to consider multiple variables before proceeding.

As a result, MR repair may not be amenable to randomization in a cardiogenic shock population, given that this decision is not typically undertaken out of the context of multiple variables.

“I am not sure that a clinical trial is ethical,” she said. She would expect that clinicians enrolling patients would only do so on a selective basis.

Alexandra J. Lansky, MD, Director of the Yale Heart and Vascular Research Program, Yale University, New Haven, Conn., also emphasized the difficulty of controlling for variables, such as the duration of cardiogenic shock, that influence decision-making.

Nevertheless, she called the data “very important” in that they at least lend some objective data for deciding whether to intervene a group of “challenging” patients not uncommonly faced in clinical practice.

Dr. Alkhouli reports financial relationships with Abbott Vascular, Boston Scientific, Johnson & Johnson, and Phillips. Dr. Asgar reports financial relationships with Abbott Vascular, Edwards Lifesciences, W.L. Gore & Associates, and Medtronic. Dr. Lasky reports no potential conflicts of interest.

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

In patients with severe mitral regurgitation (MR) and cardiogenic shock, successful transcatheter edge-to-edge repair (TEER) is associated with a substantial reduction in all-cause mortality and lower morbidity at 1 year, according to an analysis of registry data.

The data from this analysis also confirm that “successful reduction of MR is achievable with TEER in most patients with cardiogenic shock,” reported Mohamad A. Alkhouli, MD, an interventional cardiologist and professor of medicine at the Mayo Clinic, Rochester, Minn.

STS/ACC TCT registry data queried

Drawn from the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry, 3,797 patients with cardiogenic shock underwent MR repair between November 2013 and December 2021. Outcomes at 1 year were evaluable in 2,773 of these patients. For inclusion, all had to meet at least one of the definitions of cardiogenic shock, such as inotrope use or mechanical circulatory support.

At baseline, 94.5% had a MR severity of at least 3+, and most of these had 4+. Thirty days after treatment, 88.8% had MR severity of 2+ or less, the majority of which had a severity of 1+.

These data address an important question not previously well studied, according to Dr. Alkhouli. In MR patients, cardiogenic shock is associated with a high risk of death, but there has been little evidence that valve repair does not exacerbate, let alone modify, this risk.

These data support the value of intervention, which was performed in almost all patients with MitraClipä (Abbott), the only device available for most of the period in which the registry was queried. However, Dr. Alkhouli cautioned that his data are best considered “hypothesis generating.”

“We need a randomized trial,” he said at the meeting sponsored by the Cardiovascular Research Foundation. He pointed out that this is a complex population for which multiple variables might have skewed results when data are analyzed retrospectively. Not least, those MR patients with cardiogenic shock in the database considered for TEER might well have been relatively healthy and not representative of an unselected population with both MR and cardiogenic shock.

The question might be better answered by the multicenter Canadian trial CAPITAL MINOS, which has just started. Described in an article in the American Heart Journal, it has a planned enrollment of about 150 MR patients with cardiogenic shock randomized to TEER or medical therapy. Results are expected in about 1 year, according to Dr. Alkhouli.

But regarding the present analysis, Dr. Alkhouli did note that sensitivity analyses conducted within his data across risk factors, such as degenerative versus nondegenerative MR, low (< 30%) versus higher left ventricular ejection fraction (LVEF), and presence or absence of an acute coronary syndrome (ACS), consistently supported a benefit from intervention.

Also, cardiogenic shock did not appear to be a factor in device failure, according to Dr. Alkhouli, addressing a potential criticism that cardiogenic shock was an underlying reason for device failure.
 

More than 90% in NYHA class III or IV heart failure

In this study, the mean age was 73 years. More than 90% were in class III or IV heart failure in the 2 weeks prior to TEER. More than half had established coronary artery disease. Other concomitant cardiovascular morbidities, including atrial fibrillation or flutter (65%), prior MI (39%), and prior stroke or transient ischemic attach (> 10%) were well represented.

When those with device success were compared with those with device failure, the risk profile was comparable. The predicted STS (Society of Thoracic Surgeons) mortality for mitral valve repair among these two groups was 14.8% versus 15% (P = 0.97), respectively.

However, those with device failure did have a lower baseline left ventricular ejection fraction (40.7% vs. 42.9%; P = .009) and a greater prevalence of moderate-to-severe or severe MR (96.1% vs. 84.9%; P < 0.001).

The growing experience with TEER means that benefit has now been shown in several complicated MR groups, such as those with severe ventricular dysfunction, renal insufficiency, and obstructive lung disease. This was a rationale for looking at the impact or repairing MR in patients with cardiogenic shock.

It is a pressing question, according to Dr. Alkhouli. He cited studies suggesting that up to 20% of patients hospitalized for cardiogenic shock have at least moderate-to-severe MR. Conversely, cardiogenic shock is not an uncommon finding in patients with MR.

While Dr. Alkhouli acknowledged that the many variables influencing outcome in patients with MR and cardiogenic shock will make a randomized trial “challenging,” many experts echoed this concern and even expressed some skepticism about the potential for an unbiased trial.
 

Data confirm MR repair is safe during shock

“These data do show that repair of MR is safe in patients safe in patients with cardiogenic shock,” said Anita W. Asgar, MD, an interventional cardiologist associated with the Montreal Heart Institute. She noted that there was a 5- to 6-day delay among the cardiogenic shock patients prior to undergoing MR repair in this analysis, potentially reflecting an elimination of those at very high risk. Similarly, she suggested that many interventionalists are likely to consider multiple variables before proceeding.

As a result, MR repair may not be amenable to randomization in a cardiogenic shock population, given that this decision is not typically undertaken out of the context of multiple variables.

“I am not sure that a clinical trial is ethical,” she said. She would expect that clinicians enrolling patients would only do so on a selective basis.

Alexandra J. Lansky, MD, Director of the Yale Heart and Vascular Research Program, Yale University, New Haven, Conn., also emphasized the difficulty of controlling for variables, such as the duration of cardiogenic shock, that influence decision-making.

Nevertheless, she called the data “very important” in that they at least lend some objective data for deciding whether to intervene a group of “challenging” patients not uncommonly faced in clinical practice.

Dr. Alkhouli reports financial relationships with Abbott Vascular, Boston Scientific, Johnson & Johnson, and Phillips. Dr. Asgar reports financial relationships with Abbott Vascular, Edwards Lifesciences, W.L. Gore & Associates, and Medtronic. Dr. Lasky reports no potential conflicts of interest.

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

In patients with severe mitral regurgitation (MR) and cardiogenic shock, successful transcatheter edge-to-edge repair (TEER) is associated with a substantial reduction in all-cause mortality and lower morbidity at 1 year, according to an analysis of registry data.

The data from this analysis also confirm that “successful reduction of MR is achievable with TEER in most patients with cardiogenic shock,” reported Mohamad A. Alkhouli, MD, an interventional cardiologist and professor of medicine at the Mayo Clinic, Rochester, Minn.

STS/ACC TCT registry data queried

Drawn from the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry, 3,797 patients with cardiogenic shock underwent MR repair between November 2013 and December 2021. Outcomes at 1 year were evaluable in 2,773 of these patients. For inclusion, all had to meet at least one of the definitions of cardiogenic shock, such as inotrope use or mechanical circulatory support.

At baseline, 94.5% had a MR severity of at least 3+, and most of these had 4+. Thirty days after treatment, 88.8% had MR severity of 2+ or less, the majority of which had a severity of 1+.

These data address an important question not previously well studied, according to Dr. Alkhouli. In MR patients, cardiogenic shock is associated with a high risk of death, but there has been little evidence that valve repair does not exacerbate, let alone modify, this risk.

These data support the value of intervention, which was performed in almost all patients with MitraClipä (Abbott), the only device available for most of the period in which the registry was queried. However, Dr. Alkhouli cautioned that his data are best considered “hypothesis generating.”

“We need a randomized trial,” he said at the meeting sponsored by the Cardiovascular Research Foundation. He pointed out that this is a complex population for which multiple variables might have skewed results when data are analyzed retrospectively. Not least, those MR patients with cardiogenic shock in the database considered for TEER might well have been relatively healthy and not representative of an unselected population with both MR and cardiogenic shock.

The question might be better answered by the multicenter Canadian trial CAPITAL MINOS, which has just started. Described in an article in the American Heart Journal, it has a planned enrollment of about 150 MR patients with cardiogenic shock randomized to TEER or medical therapy. Results are expected in about 1 year, according to Dr. Alkhouli.

But regarding the present analysis, Dr. Alkhouli did note that sensitivity analyses conducted within his data across risk factors, such as degenerative versus nondegenerative MR, low (< 30%) versus higher left ventricular ejection fraction (LVEF), and presence or absence of an acute coronary syndrome (ACS), consistently supported a benefit from intervention.

Also, cardiogenic shock did not appear to be a factor in device failure, according to Dr. Alkhouli, addressing a potential criticism that cardiogenic shock was an underlying reason for device failure.
 

More than 90% in NYHA class III or IV heart failure

In this study, the mean age was 73 years. More than 90% were in class III or IV heart failure in the 2 weeks prior to TEER. More than half had established coronary artery disease. Other concomitant cardiovascular morbidities, including atrial fibrillation or flutter (65%), prior MI (39%), and prior stroke or transient ischemic attach (> 10%) were well represented.

When those with device success were compared with those with device failure, the risk profile was comparable. The predicted STS (Society of Thoracic Surgeons) mortality for mitral valve repair among these two groups was 14.8% versus 15% (P = 0.97), respectively.

However, those with device failure did have a lower baseline left ventricular ejection fraction (40.7% vs. 42.9%; P = .009) and a greater prevalence of moderate-to-severe or severe MR (96.1% vs. 84.9%; P < 0.001).

The growing experience with TEER means that benefit has now been shown in several complicated MR groups, such as those with severe ventricular dysfunction, renal insufficiency, and obstructive lung disease. This was a rationale for looking at the impact or repairing MR in patients with cardiogenic shock.

It is a pressing question, according to Dr. Alkhouli. He cited studies suggesting that up to 20% of patients hospitalized for cardiogenic shock have at least moderate-to-severe MR. Conversely, cardiogenic shock is not an uncommon finding in patients with MR.

While Dr. Alkhouli acknowledged that the many variables influencing outcome in patients with MR and cardiogenic shock will make a randomized trial “challenging,” many experts echoed this concern and even expressed some skepticism about the potential for an unbiased trial.
 

Data confirm MR repair is safe during shock

“These data do show that repair of MR is safe in patients safe in patients with cardiogenic shock,” said Anita W. Asgar, MD, an interventional cardiologist associated with the Montreal Heart Institute. She noted that there was a 5- to 6-day delay among the cardiogenic shock patients prior to undergoing MR repair in this analysis, potentially reflecting an elimination of those at very high risk. Similarly, she suggested that many interventionalists are likely to consider multiple variables before proceeding.

As a result, MR repair may not be amenable to randomization in a cardiogenic shock population, given that this decision is not typically undertaken out of the context of multiple variables.

“I am not sure that a clinical trial is ethical,” she said. She would expect that clinicians enrolling patients would only do so on a selective basis.

Alexandra J. Lansky, MD, Director of the Yale Heart and Vascular Research Program, Yale University, New Haven, Conn., also emphasized the difficulty of controlling for variables, such as the duration of cardiogenic shock, that influence decision-making.

Nevertheless, she called the data “very important” in that they at least lend some objective data for deciding whether to intervene a group of “challenging” patients not uncommonly faced in clinical practice.

Dr. Alkhouli reports financial relationships with Abbott Vascular, Boston Scientific, Johnson & Johnson, and Phillips. Dr. Asgar reports financial relationships with Abbott Vascular, Edwards Lifesciences, W.L. Gore & Associates, and Medtronic. Dr. Lasky reports no potential conflicts of interest.

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

Even a little walking may help avert serious illness and death, and a brisk stroll may be especially beneficial, according to a study of nearly 80,000 middle-aged and older adults.

Each additional 2,000 steps per day – up to 10,000 – was associated with 8% to 11% fewer deaths and less heart disease and cancer, the researchers found. Walking quickly had an even stronger link to lower health risks.

The findings were reported in JAMA Internal Medicine. In a separate paper, published in JAMA Neurology, the researchers reported associations between walking and reduced risk of dementia.
 

Moving faster provides a health ‘bonus’

The findings expand on evidence in smaller studies of middle-aged individuals and older women that suggested health benefits from covering less than the widely promoted target of 10,000 steps a day.

The new study supports the ideas that “every step counts” and moving faster provides a health “bonus,” said one of its co-lead authors, Borja del Pozo Cruz, PhD, an associate professor at the University of Southern Denmark, Odense, and a senior researcher in health at the University of Cadiz, Spain.

Dr. Del Pozo Cruz and his coauthors analyzed median daily step counts for 78,500 adults aged 40-79 years in the U.K. Biobank database who agreed to wear an accelerometer for 1 week. Participants’ average age was 61. Fifty-five percent were women and 97% were White.

Steps were categorized as “incidental,” defined as a pace of less than 40 per minute, and “purposeful,” ones taken at the pace of 40 or more per minute. Researchers also calculated peak 30-minute cadence, the average of an individual’s 30 most active minutes in a day.

Participants’ health records were reviewed after 7 years. Each additional 2,000 steps taken was associated with lower all-cause mortality (mean rate of change [MRC] in the hazard ratio, –0.08; 95% confidence interval, –0.11 to –0.06); cardiovascular mortality (MRC, –0.10; 95% CI, –0.15 to –0.06), and cancer mortality (MRC, –0.11; 95% CI, –0.15 to –0.06).

Similar incremental reductions were observed in the incidence of heart disease, defined as fatal and nonfatal coronary heart disease, stroke, and heart failure; and a composite cancer outcome of 13 sites shown to be associated with low physical activity.

Both incidental and purposeful steps were linked to lower rates of mortality and disease. Particularly encouraging, the researchers said, was the benefit associated with incidental steps, which might be more feasible for some individuals than a planned walk.

The association with better outcomes was especially strong for peak-30 cadence, with individuals in the top fifth of intensity having a 34% lower mortality rate compared with those in the bottom fifth – an observation that researchers wrote “reflects the importance of the natural best effort relative to the individual’s capability.”

The analysis adjusted for a variety of factors including age, sex, race, smoking, alcohol use, fruit and vegetable consumption, medication use, family history of cardiovascular disease or cancer, and sleep quality. It also excluded participants who had deaths and illnesses within 2 years of a step assessment to minimize the problem of reverse causation, in which existing health problems cause participants to move less.
 

Data contribute evidence toward step count recommendations

The data are observational and do not prove cause and effect, the researchers noted. Still, the authors said the study “contributes critical evidence toward step count–based recommendations” for physical activity.

Guidelines of the United States and the World Health Organization recommend 150 minutes of moderately intense activity or 75 minutes of vigorous activity weekly plus strength training twice a week.

Given the proliferation of activity trackers in phones and watches, recommendations based on steps could be especially useful for individuals who don’t intentionally record their physical activity, the researchers wrote.

“It’s nice to have a study that puts some science behind steps counts,” cardiologist Nieca Goldberg, MD, a clinical associate professor of medicine at New York University, and a spokesperson for the American Heart Association, said of the findings.

Particularly important, said Dr. Goldberg, who was not involved in the study, is the lack of a minimum threshold for health benefits, since the 10,000-step target may be daunting for some individuals.

Only one in five participants in this latest study achieved 10,000 steps per day, according to the paper.

The authors wrote that promotion of lower step targets “may provide a more realistic and achievable goal for the general adult population,” and longevity gains “may be maximized simply by shifting away from the least-active end of the step-count distribution.”

Dr. Goldberg put it this way: “Take a walk. Try to aspire to 10,000 steps. But if you can only do 6,000 or 8,000, you get benefit there, too.”

Cathy Handy Marshall, MD, MPH, an assistant professor of oncology at Johns Hopkins University, Baltimore, who was not involved in the new study, said the findings can be used to guide “exercise prescriptions,” but more research is needed to tailor recommendations, particularly for individuals who cannot achieve high step counts.

Dr. Del Pozo Cruz said the findings need to be replicated in other populations.

The study authors, Dr. Goldberg, and Dr. Handy Marshall reported no relevant competing interests.

Even a little walking may help avert serious illness and death, and a brisk stroll may be especially beneficial, according to a study of nearly 80,000 middle-aged and older adults.

Each additional 2,000 steps per day – up to 10,000 – was associated with 8% to 11% fewer deaths and less heart disease and cancer, the researchers found. Walking quickly had an even stronger link to lower health risks.

The findings were reported in JAMA Internal Medicine. In a separate paper, published in JAMA Neurology, the researchers reported associations between walking and reduced risk of dementia.
 

Moving faster provides a health ‘bonus’

The findings expand on evidence in smaller studies of middle-aged individuals and older women that suggested health benefits from covering less than the widely promoted target of 10,000 steps a day.

The new study supports the ideas that “every step counts” and moving faster provides a health “bonus,” said one of its co-lead authors, Borja del Pozo Cruz, PhD, an associate professor at the University of Southern Denmark, Odense, and a senior researcher in health at the University of Cadiz, Spain.

Dr. Del Pozo Cruz and his coauthors analyzed median daily step counts for 78,500 adults aged 40-79 years in the U.K. Biobank database who agreed to wear an accelerometer for 1 week. Participants’ average age was 61. Fifty-five percent were women and 97% were White.

Steps were categorized as “incidental,” defined as a pace of less than 40 per minute, and “purposeful,” ones taken at the pace of 40 or more per minute. Researchers also calculated peak 30-minute cadence, the average of an individual’s 30 most active minutes in a day.

Participants’ health records were reviewed after 7 years. Each additional 2,000 steps taken was associated with lower all-cause mortality (mean rate of change [MRC] in the hazard ratio, –0.08; 95% confidence interval, –0.11 to –0.06); cardiovascular mortality (MRC, –0.10; 95% CI, –0.15 to –0.06), and cancer mortality (MRC, –0.11; 95% CI, –0.15 to –0.06).

Similar incremental reductions were observed in the incidence of heart disease, defined as fatal and nonfatal coronary heart disease, stroke, and heart failure; and a composite cancer outcome of 13 sites shown to be associated with low physical activity.

Both incidental and purposeful steps were linked to lower rates of mortality and disease. Particularly encouraging, the researchers said, was the benefit associated with incidental steps, which might be more feasible for some individuals than a planned walk.

The association with better outcomes was especially strong for peak-30 cadence, with individuals in the top fifth of intensity having a 34% lower mortality rate compared with those in the bottom fifth – an observation that researchers wrote “reflects the importance of the natural best effort relative to the individual’s capability.”

The analysis adjusted for a variety of factors including age, sex, race, smoking, alcohol use, fruit and vegetable consumption, medication use, family history of cardiovascular disease or cancer, and sleep quality. It also excluded participants who had deaths and illnesses within 2 years of a step assessment to minimize the problem of reverse causation, in which existing health problems cause participants to move less.
 

Data contribute evidence toward step count recommendations

The data are observational and do not prove cause and effect, the researchers noted. Still, the authors said the study “contributes critical evidence toward step count–based recommendations” for physical activity.

Guidelines of the United States and the World Health Organization recommend 150 minutes of moderately intense activity or 75 minutes of vigorous activity weekly plus strength training twice a week.

Given the proliferation of activity trackers in phones and watches, recommendations based on steps could be especially useful for individuals who don’t intentionally record their physical activity, the researchers wrote.

“It’s nice to have a study that puts some science behind steps counts,” cardiologist Nieca Goldberg, MD, a clinical associate professor of medicine at New York University, and a spokesperson for the American Heart Association, said of the findings.

Particularly important, said Dr. Goldberg, who was not involved in the study, is the lack of a minimum threshold for health benefits, since the 10,000-step target may be daunting for some individuals.

Only one in five participants in this latest study achieved 10,000 steps per day, according to the paper.

The authors wrote that promotion of lower step targets “may provide a more realistic and achievable goal for the general adult population,” and longevity gains “may be maximized simply by shifting away from the least-active end of the step-count distribution.”

Dr. Goldberg put it this way: “Take a walk. Try to aspire to 10,000 steps. But if you can only do 6,000 or 8,000, you get benefit there, too.”

Cathy Handy Marshall, MD, MPH, an assistant professor of oncology at Johns Hopkins University, Baltimore, who was not involved in the new study, said the findings can be used to guide “exercise prescriptions,” but more research is needed to tailor recommendations, particularly for individuals who cannot achieve high step counts.

Dr. Del Pozo Cruz said the findings need to be replicated in other populations.

The study authors, Dr. Goldberg, and Dr. Handy Marshall reported no relevant competing interests.

Even a little walking may help avert serious illness and death, and a brisk stroll may be especially beneficial, according to a study of nearly 80,000 middle-aged and older adults.

Each additional 2,000 steps per day – up to 10,000 – was associated with 8% to 11% fewer deaths and less heart disease and cancer, the researchers found. Walking quickly had an even stronger link to lower health risks.

The findings were reported in JAMA Internal Medicine. In a separate paper, published in JAMA Neurology, the researchers reported associations between walking and reduced risk of dementia.
 

Moving faster provides a health ‘bonus’

The findings expand on evidence in smaller studies of middle-aged individuals and older women that suggested health benefits from covering less than the widely promoted target of 10,000 steps a day.

The new study supports the ideas that “every step counts” and moving faster provides a health “bonus,” said one of its co-lead authors, Borja del Pozo Cruz, PhD, an associate professor at the University of Southern Denmark, Odense, and a senior researcher in health at the University of Cadiz, Spain.

Dr. Del Pozo Cruz and his coauthors analyzed median daily step counts for 78,500 adults aged 40-79 years in the U.K. Biobank database who agreed to wear an accelerometer for 1 week. Participants’ average age was 61. Fifty-five percent were women and 97% were White.

Steps were categorized as “incidental,” defined as a pace of less than 40 per minute, and “purposeful,” ones taken at the pace of 40 or more per minute. Researchers also calculated peak 30-minute cadence, the average of an individual’s 30 most active minutes in a day.

Participants’ health records were reviewed after 7 years. Each additional 2,000 steps taken was associated with lower all-cause mortality (mean rate of change [MRC] in the hazard ratio, –0.08; 95% confidence interval, –0.11 to –0.06); cardiovascular mortality (MRC, –0.10; 95% CI, –0.15 to –0.06), and cancer mortality (MRC, –0.11; 95% CI, –0.15 to –0.06).

Similar incremental reductions were observed in the incidence of heart disease, defined as fatal and nonfatal coronary heart disease, stroke, and heart failure; and a composite cancer outcome of 13 sites shown to be associated with low physical activity.

Both incidental and purposeful steps were linked to lower rates of mortality and disease. Particularly encouraging, the researchers said, was the benefit associated with incidental steps, which might be more feasible for some individuals than a planned walk.

The association with better outcomes was especially strong for peak-30 cadence, with individuals in the top fifth of intensity having a 34% lower mortality rate compared with those in the bottom fifth – an observation that researchers wrote “reflects the importance of the natural best effort relative to the individual’s capability.”

The analysis adjusted for a variety of factors including age, sex, race, smoking, alcohol use, fruit and vegetable consumption, medication use, family history of cardiovascular disease or cancer, and sleep quality. It also excluded participants who had deaths and illnesses within 2 years of a step assessment to minimize the problem of reverse causation, in which existing health problems cause participants to move less.
 

Data contribute evidence toward step count recommendations

The data are observational and do not prove cause and effect, the researchers noted. Still, the authors said the study “contributes critical evidence toward step count–based recommendations” for physical activity.

Guidelines of the United States and the World Health Organization recommend 150 minutes of moderately intense activity or 75 minutes of vigorous activity weekly plus strength training twice a week.

Given the proliferation of activity trackers in phones and watches, recommendations based on steps could be especially useful for individuals who don’t intentionally record their physical activity, the researchers wrote.

“It’s nice to have a study that puts some science behind steps counts,” cardiologist Nieca Goldberg, MD, a clinical associate professor of medicine at New York University, and a spokesperson for the American Heart Association, said of the findings.

Particularly important, said Dr. Goldberg, who was not involved in the study, is the lack of a minimum threshold for health benefits, since the 10,000-step target may be daunting for some individuals.

Only one in five participants in this latest study achieved 10,000 steps per day, according to the paper.

The authors wrote that promotion of lower step targets “may provide a more realistic and achievable goal for the general adult population,” and longevity gains “may be maximized simply by shifting away from the least-active end of the step-count distribution.”

Dr. Goldberg put it this way: “Take a walk. Try to aspire to 10,000 steps. But if you can only do 6,000 or 8,000, you get benefit there, too.”

Cathy Handy Marshall, MD, MPH, an assistant professor of oncology at Johns Hopkins University, Baltimore, who was not involved in the new study, said the findings can be used to guide “exercise prescriptions,” but more research is needed to tailor recommendations, particularly for individuals who cannot achieve high step counts.

Dr. Del Pozo Cruz said the findings need to be replicated in other populations.

The study authors, Dr. Goldberg, and Dr. Handy Marshall reported no relevant competing interests.